diff --git "a/pv_train.tsv" "b/pv_train.tsv"
new file mode 100644--- /dev/null
+++ "b/pv_train.tsv"
@@ -0,0 +1,783843 @@
+Comparison	O
+with	O
+alkaline	B-GENE
+phosphatases	I-GENE
+and	O
+5	B-GENE
+-	I-GENE
+nucleotidase	I-GENE
+
+Pharmacologic	O
+aspects	O
+of	O
+neonatal	O
+hyperbilirubinemia	O
+.	O
+
+When	O
+CSF	O
+[	O
+HCO3	O
+-	O
+]	O
+is	O
+shown	O
+as	O
+a	O
+function	O
+of	O
+CSF	O
+PCO2	O
+the	O
+data	O
+of	O
+K	O
+-	O
+depleted	O
+rats	O
+are	O
+no	O
+longer	O
+displaced	O
+when	O
+compared	O
+to	O
+controls	O
+but	O
+still	O
+have	O
+a	O
+significantly	O
+greater	O
+slope	O
+(	O
+1	O
+.	O
+21	O
++	O
+/	O
+-	O
+0	O
+.	O
+23	O
+vs	O
+.	O
+
+Flurazepam	O
+thus	O
+appears	O
+to	O
+be	O
+an	O
+effective	O
+hypnotic	O
+drug	O
+with	O
+the	O
+optimum	O
+dose	O
+for	O
+use	O
+in	O
+general	O
+practice	O
+being	O
+15	O
+mg	O
+at	O
+night	O
+.	O
+
+Beta	O
+blocking	O
+agents	O
+.	O
+
+When	O
+extracorporeal	O
+CO2	O
+removal	O
+approximated	O
+CO2	O
+production	O
+(	O
+VCO2	O
+)	O
+,	O
+alveolar	O
+ventilation	O
+almost	O
+ceased	O
+.	O
+
+Intravenous	O
+administration	O
+(	O
+25	O
+mg	O
+/	O
+kg	O
+)	O
+of	O
+carbonic	B-GENE
+anhydrase	I-GENE
+inhibitors	O
+(	O
+acetazolamide	O
+,	O
+methazolamide	O
+,	O
+dichlorphenamide	O
+,	O
+sulthiame	O
+)	O
+induced	O
+an	O
+early	O
+important	O
+rise	O
+of	O
+cortical	O
+p	O
+O2	O
+,	O
+which	O
+is	O
+not	O
+dependent	O
+on	O
+increase	O
+of	O
+p	O
+O2	O
+and	O
+p	O
+CO2	O
+and	O
+decrease	O
+of	O
+pH	O
+in	O
+arterial	O
+blood	O
+.	O
+
+Teratological	O
+study	O
+of	O
+etoperidone	O
+in	O
+the	O
+rat	O
+and	O
+rabbit	O
+.	O
+
+Colorectal	O
+polyps	O
+should	O
+be	O
+removed	O
+endoscopically	O
+whenever	O
+possible	O
+.	O
+
+The	O
+variable	O
+HMG	B-GENE
+dosage	O
+regimen	O
+was	O
+found	O
+to	O
+offer	O
+no	O
+advantages	O
+when	O
+compared	O
+with	O
+our	O
+standard	O
+daily	O
+dosage	O
+regimen	O
+.	O
+
+When	O
+the	O
+CO2	O
+content	O
+reached	O
+9	O
+Vol	O
+%	O
+the	O
+animals	O
+became	O
+apathic	O
+and	O
+lost	O
+body	O
+weight	O
+.	O
+
+Serum	B-GENE
+gamma	I-GENE
+glutamyltransferase	I-GENE
+in	O
+the	O
+diagnosis	O
+of	O
+liver	O
+disease	O
+in	O
+cattle	O
+.	O
+
+By	O
+contrast	O
+,	O
+secretory	B-GENE
+HI	I-GENE
+antibodies	I-GENE
+were	O
+not	O
+demonstrated	O
+at	O
+the	O
+onset	O
+of	O
+illness	O
+in	O
+any	O
+of	O
+the	O
+patients	O
+,	O
+but	O
+their	O
+formation	O
+started	O
+early	O
+and	O
+the	O
+antibodies	O
+reached	O
+maximal	O
+levels	O
+about	O
+10	O
+days	O
+after	O
+onset	O
+of	O
+illness	O
+.	O
+
+With	O
+the	O
+exception	O
+of	O
+virus	O
+assay	O
+and	O
+quantitation	O
+,	O
+these	O
+methods	O
+are	O
+simple	O
+and	O
+inexpensive	O
+enough	O
+to	O
+be	O
+done	O
+in	O
+typical	O
+shellfish	O
+microbiology	O
+laboratories	O
+.	O
+
+Characteristics	O
+of	O
+lipase	B-GENE
+activity	O
+.	O
+
+Takayasu	O
+'	O
+s	O
+disease	O
+:	O
+association	O
+with	O
+HLA	B-GENE
+-	I-GENE
+B5	I-GENE
+.	O
+
+SGPT	B-GENE
+,	O
+SGOT	B-GENE
+,	O
+and	O
+alkaline	B-GENE
+phosphatase	I-GENE
+concentrations	O
+were	O
+essentially	O
+normal	O
+in	O
+all	O
+subjects	O
+.	O
+
+Gamma	B-GENE
+glutamyl	I-GENE
+transpeptidase	I-GENE
+(	O
+GGTP	B-GENE
+)	O
+activity	O
+in	O
+the	O
+seminal	O
+fluid	O
+
+Patients	O
+with	O
+Parkinson	O
+'	O
+s	O
+disease	O
+showed	O
+a	O
+relatively	O
+high	O
+incidence	O
+to	O
+psychoses	O
+during	O
+drug	O
+treatment	O
+(	O
+51	O
+.	O
+47	O
+%	O
+)	O
+.	O
+
+Selective	O
+stimulation	O
+of	O
+central	O
+alpha	B-GENE
+-	I-GENE
+autoreceptors	I-GENE
+following	O
+treatment	O
+with	O
+alpha	O
+-	O
+methyldopa	O
+and	O
+FLA	O
+136	O
+.	O
+
+Anti	O
+-	O
+anxiety	O
+action	O
+of	O
+diazepam	O
+after	O
+intra	O
+-	O
+amygdaloid	O
+application	O
+in	O
+the	O
+rat	O
+.	O
+
+Abstracts	O
+.	O
+
+Removal	O
+of	O
+thick	O
+,	O
+permanently	O
+altered	O
+mucoas	O
+is	O
+recommended	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+squamous	O
+epithelium	O
+.	O
+
+An	O
+IgG	B-GENE
+monoclonal	O
+gammopathy	O
+was	O
+present	O
+in	O
+the	O
+serum	O
+of	O
+4	O
+patients	O
+and	O
+Bence	O
+-	O
+Joanes	O
+proteinuria	O
+was	O
+found	O
+in	O
+1	O
+patient	O
+.	O
+
+Studies	O
+on	O
+immunoglobulin	B-GENE
+E	I-GENE
+:	O
+the	O
+impact	O
+of	O
+a	O
+sojourn	O
+with	O
+Professor	O
+Dan	O
+H	O
+.	O
+
+Peroxydase	B-GENE
+reaction	O
+stains	O
+were	O
+negative	O
+,	O
+chloroacetate	B-GENE
+esterase	I-GENE
+were	O
+strongly	O
+positive	O
+.	O
+
+Ten	O
+out	O
+-	O
+patients	O
+with	O
+pustulosis	O
+palmaris	O
+et	O
+plantaris	O
+were	O
+examined	O
+with	O
+direct	O
+immunofluorescence	O
+(	O
+IF	O
+)	O
+technique	O
+for	O
+deposition	O
+of	O
+fibrinogen	B-GENE
+,	O
+fibrin	B-GENE
+or	O
+its	O
+degradation	O
+products	O
+(	O
+FR	B-GENE
+-	I-GENE
+antigen	I-GENE
+)	O
+in	O
+affected	O
+and	O
+unaffected	O
+skin	O
+,	O
+together	O
+with	O
+heparin	O
+-	O
+precipitable	O
+fraction	O
+(	O
+HPF	O
+)	O
+,	O
+cryoglobulin	B-GENE
+and	O
+total	O
+plasma	O
+fibrinogen	B-GENE
+in	O
+the	O
+blood	O
+.	O
+
+Of	O
+600	O
+mediastinoscopies	O
+carried	O
+out	O
+from	O
+1966	O
+to	O
+1973	O
+,	O
+479	O
+were	O
+performed	O
+to	O
+assess	O
+the	O
+operability	O
+of	O
+a	O
+pulmonary	O
+carcinoma	O
+.	O
+
+A	O
+mixture	O
+of	O
+human	B-GENE
+albumin	I-GENE
+5	O
+%	O
+and	O
+hydroxy	O
+-	O
+ethyl	O
+-	O
+starch	O
+was	O
+used	O
+as	O
+a	O
+solution	O
+for	O
+dilution	O
+.	O
+
+In	O
+the	O
+matched	O
+control	O
+group	O
+the	O
+acquisition	O
+-	O
+rate	O
+of	O
+both	O
+symptomatic	O
+and	O
+asymptomatic	O
+0acteriuria	O
+was	O
+over	O
+12	O
+%	O
+,	O
+a	O
+figure	O
+similar	O
+to	O
+the	O
+percentage	O
+of	O
+women	O
+present	O
+in	O
+the	O
+practice	O
+population	O
+during	O
+one	O
+year	O
+with	O
+transient	O
+,	O
+symptomatic	O
+,	O
+and	O
+persistent	O
+A	O
+.	O
+B	O
+.	O
+
+Late	O
+complications	O
+of	O
+catheterisation	O
+for	O
+intravenous	O
+nutrition	O
+.	O
+
+Prenatal	O
+diagnosis	O
+of	O
+galactosaemia	O
+.	O
+
+Sings	O
+which	O
+are	O
+indicative	O
+of	O
+metaplastic	O
+erythropoiesis	O
+are	O
+absent	O
+.	O
+
+False	O
+positive	O
+amniotic	B-GENE
+fluid	I-GENE
+alpha	I-GENE
+fetoprotein	I-GENE
+levels	O
+resulting	O
+from	O
+contamination	O
+with	O
+fetal	O
+blood	O
+:	O
+results	O
+of	O
+an	O
+experiment	O
+.	O
+
+Serum	O
+-	O
+ferritin	B-GENE
+in	O
+diagnosis	O
+of	O
+haemochromatosis	O
+.	O
+
+In	O
+2	O
+subjects	O
+the	O
+phytomitogen	O
+reactivity	O
+of	O
+the	O
+lymphocytes	O
+was	O
+improved	O
+after	O
+treatment	O
+.	O
+
+Patients	O
+at	O
+risk	O
+of	O
+hypothyroidism	O
+.	O
+
+Albumin	B-GENE
+and	O
+cyclic	O
+AMP	O
+levels	O
+in	O
+peritoneal	O
+fluids	O
+in	O
+the	O
+child	O
+
+Preface	O
+.	O
+
+Thirty	O
+-	O
+five	O
+strains	O
+of	O
+Legionnaires	O
+'	O
+disease	O
+bacteria	O
+were	O
+shown	O
+to	O
+belong	O
+in	O
+four	O
+distinct	O
+serologic	O
+groups	O
+on	O
+the	O
+basis	O
+of	O
+findings	O
+obtained	O
+with	O
+direct	O
+fluorescent	O
+antibody	O
+testing	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+factor	B-GENE
+IX	I-GENE
+activity	O
+is	O
+decreased	O
+in	O
+coumarin	O
+treatment	O
+with	O
+factor	B-GENE
+IX	I-GENE
+antigen	O
+remaining	O
+normal	O
+.	O
+
+The	O
+concentration	O
+of	O
+alpha	B-GENE
+2	I-GENE
+-	I-GENE
+macroglobulin	I-GENE
+,	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+antitrypsin	I-GENE
+,	O
+plasminogen	B-GENE
+,	O
+C3	B-GENE
+-	I-GENE
+complement	I-GENE
+,	O
+fibrinogen	B-GENE
+degradation	I-GENE
+products	I-GENE
+(	O
+FDP	B-GENE
+)	O
+and	O
+fibrinolytic	O
+activity	O
+,	O
+were	O
+studied	O
+in	O
+the	O
+aqueous	O
+humour	O
+and	O
+serum	O
+from	O
+nine	O
+patients	O
+with	O
+Fuchs	O
+'	O
+endothelial	O
+dystrophy	O
+,	O
+17	O
+patients	O
+with	O
+uncomplicated	O
+senile	O
+cataract	O
+and	O
+in	O
+the	O
+secondary	O
+aqueous	O
+from	O
+six	O
+cataract	O
+patients	O
+.	O
+
+Only	O
+17	O
+%	O
+of	O
+all	O
+patients	O
+admitted	O
+it	O
+at	O
+all	O
+times	O
+.	O
+
+Prazosin	O
+alone	O
+was	O
+effective	O
+in	O
+volume	O
+responsive	O
+patients	O
+at	O
+a	O
+dose	O
+of	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+mg	O
+daily	O
+.	O
+
+T4	O
+and	O
+FT4I	O
+followed	O
+parallel	O
+courses	O
+in	O
+both	O
+groups	O
+;	O
+during	O
+the	O
+first	O
+45	O
+days	O
+,	O
+however	O
+,	O
+the	O
+values	O
+were	O
+significantly	O
+lower	O
+in	O
+premature	O
+infants	O
+under	O
+34	O
+weeks	O
+'	O
+EGA	O
+than	O
+in	O
+term	O
+infants	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+A	O
+three	O
+-	O
+phased	O
+analysis	O
+of	O
+treatment	O
+plans	O
+for	O
+45	O
+patients	O
+was	O
+undertaken	O
+.	O
+
+Aspirin	O
+intolerance	O
+:	O
+unaltered	O
+susceptibility	O
+of	O
+platelet	B-GENE
+cyclo	I-GENE
+-	I-GENE
+oxygenase	I-GENE
+to	O
+inhibition	O
+by	O
+aspirin	O
+in	O
+vitro	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+cynomolgus	O
+monkeys	O
+are	O
+either	O
+less	O
+sensitive	O
+or	O
+respond	O
+differently	O
+than	O
+rhesus	O
+monkeys	O
+to	O
+some	O
+of	O
+the	O
+pharmacological	O
+effects	O
+of	O
+norcocaine	O
+.	O
+
+59	O
+cases	O
+of	O
+surgically	O
+resectable	O
+cancers	O
+(	O
+T1	O
+,	O
+T2	O
+,	O
+T3	O
+,	O
+N0	O
+,	O
+N1	O
+)	O
+had	O
+a	O
+minimum	O
+followup	O
+of	O
+two	O
+years	O
+(	O
+average	O
+4	O
+years	O
++	O
+/	O
+-	O
+3	O
+months	O
+)	O
+.	O
+
+The	O
+effect	O
+of	O
+CBZ	O
+and	O
+DPH	O
+can	O
+be	O
+explained	O
+by	O
+interference	O
+with	O
+thyroid	O
+hormone	O
+binding	O
+to	O
+TBG	B-GENE
+combined	O
+with	O
+enzyme	O
+-	O
+induced	O
+increased	O
+metabolic	O
+clearance	O
+rate	O
+of	O
+thyroid	O
+hormones	O
+without	O
+homeostatic	O
+maintenance	O
+of	O
+premedication	O
+levels	O
+of	O
+FT4	O
+and	O
+FT3	O
+.	O
+
+The	O
+present	O
+research	O
+evaluated	O
+the	O
+possibility	O
+that	O
+polyethylene	O
+glycol	O
+400	O
+(	O
+PEG	O
+400	O
+)	O
+might	O
+be	O
+efficacious	O
+,	O
+toxic	O
+,	O
+or	O
+both	O
+.	O
+
+According	O
+to	O
+their	O
+functional	O
+properties	O
+the	O
+latter	O
+neurons	O
+were	O
+subdivided	O
+into	O
+:	O
+(	O
+a	O
+)	O
+neurons	O
+responding	O
+to	O
+stimuli	O
+near	O
+the	O
+eyes	O
+;	O
+(	O
+b	O
+)	O
+neurons	O
+triggered	O
+by	O
+complex	O
+visual	O
+stimuli	O
+;	O
+(	O
+c	O
+)	O
+neurons	O
+inhibited	O
+by	O
+visual	O
+stimuli	O
+.	O
+
+Pentobarbital	O
+(	O
+1	O
+,	O
+3	O
+,	O
+10	O
+,	O
+and	O
+17	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+was	O
+also	O
+tested	O
+in	O
+combination	O
+with	O
+rate	O
+-	O
+decreasing	O
+doses	O
+of	O
+normeperidine	O
+(	O
+17	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+anileridine	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+alphaprodine	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+and	O
+fentanyl	O
+(	O
+0	O
+.	O
+3	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+Pb	O
+foil	O
+(	O
+0	O
+.	O
+55	O
+gcm	O
+-	O
+2	O
+)	O
+provided	O
+the	O
+best	O
+overall	O
+improvement	O
+.	O
+
+An	O
+anatomical	O
+and	O
+histochemical	O
+study	O
+has	O
+been	O
+undertaken	O
+and	O
+as	O
+a	O
+result	O
+emphasis	O
+is	O
+given	O
+to	O
+recent	O
+hypotheses	O
+that	O
+suggest	O
+there	O
+are	O
+similarities	O
+with	O
+Type	O
+IV	O
+glycogen	O
+storage	O
+disease	O
+(	O
+Andersen	O
+'	O
+s	O
+disease	O
+)	O
+which	O
+,	O
+although	O
+clinically	O
+distinct	O
+,	O
+has	O
+the	O
+same	O
+enzyme	O
+defect	O
+.	O
+
+All	O
+groups	O
+were	O
+tested	O
+in	O
+a	O
+Hebb	O
+-	O
+Williams	O
+maze	O
+at	O
+100	O
+approximately	O
+10	O
+days	O
+of	O
+age	O
+.	O
+
+Erythromycin	O
+and	O
+clindamycin	O
+resistance	O
+in	O
+Corynebacterium	O
+diphtheriae	O
+from	O
+skin	O
+lesions	O
+.	O
+
+Imposed	O
+angular	O
+displacements	O
+of	O
+monkey	O
+'	O
+s	O
+wrist	O
+produce	O
+three	O
+major	O
+peaks	O
+of	O
+activity	O
+(	O
+terms	O
+M1	O
+,	O
+M2	O
+,	O
+and	O
+M3	O
+peaks	O
+)	O
+in	O
+the	O
+averaged	O
+gross	O
+EMG	O
+activity	O
+ot	O
+the	O
+stretched	O
+muscles	O
+.	O
+
+Hemolytic	O
+disease	O
+of	O
+African	O
+newborn	O
+.	O
+
+In	O
+this	O
+animal	O
+,	O
+infected	O
+with	O
+what	O
+was	O
+judged	O
+previously	O
+to	O
+be	O
+the	O
+less	O
+virulent	O
+of	O
+the	O
+two	O
+T	O
+.	O
+cruzi	O
+stocks	O
+used	O
+(	O
+'	O
+strain	O
+7	O
+'	O
+)	O
+,	O
+there	O
+was	O
+severe	O
+myocarditis	O
+,	O
+with	O
+myofibre	O
+degeneration	O
+,	O
+and	O
+lesions	O
+of	O
+the	O
+oesophagus	O
+.	O
+
+The	O
+majority	O
+of	O
+MRF	O
+units	O
+were	O
+behaviorally	O
+incongruent	O
+;	O
+in	O
+the	O
+most	O
+frequently	O
+observed	O
+case	O
+,	O
+their	O
+activity	O
+failed	O
+to	O
+change	O
+reliably	O
+when	O
+behavior	O
+habituated	O
+.	O
+
+Variability	O
+within	O
+Down	O
+'	O
+s	O
+syndrome	O
+(	O
+trisomy	O
+-	O
+21	O
+)	O
+:	O
+empirically	O
+observed	O
+sex	O
+differences	O
+in	O
+IQs	O
+.	O
+
+VII	O
+.	O
+
+Several	O
+demographic	O
+indices	O
+of	O
+isolated	O
+populations	O
+in	O
+Uzbekistan	O
+
+2	O
+.	O
+-	O
+-	O
+concepts	O
+of	O
+higher	O
+nervous	O
+function	O
+in	O
+the	O
+USSR	O
+.	O
+
+The	O
+maintenance	O
+of	O
+increased	O
+myocardial	O
+capillary	O
+density	O
+required	O
+a	O
+similar	O
+amount	O
+of	O
+exercise	O
+,	O
+and	O
+at	O
+least	O
+1	O
+h	O
+of	O
+exercise	O
+once	O
+a	O
+week	O
+was	O
+necessary	O
+to	O
+maintain	O
+the	O
+enlargement	O
+of	O
+ECA	O
+.	O
+20	O
+
+These	O
+observations	O
+have	O
+led	O
+us	O
+to	O
+conclude	O
+that	O
+an	O
+elevated	O
+VIII	O
+-	O
+ratio	O
+is	O
+a	O
+very	O
+sensitive	O
+indicator	O
+of	O
+intravascular	O
+coagulation	O
+.	O
+
+Eight	O
+hours	O
+after	O
+the	O
+administration	O
+of	O
+colchicine	O
+,	O
+the	O
+serum	B-GENE
+ceruloplasmin	I-GENE
+level	O
+began	O
+to	O
+rise	O
+again	O
+in	O
+female	O
+rats	O
+,	O
+but	O
+not	O
+in	O
+male	O
+rats	O
+.	O
+
+Radioimmunoassays	O
+of	O
+pregnenolone	O
+,	O
+progesterone	O
+,	O
+dehydroepiandrosterone	O
+(	O
+DHA	O
+)	O
+16	O
+alpha	O
+-	O
+hydroxy	O
+-	O
+DHA	O
+,	O
+estriol	O
+,	O
+and	O
+cortisol	O
+were	O
+performed	O
+on	O
+a	O
+total	O
+of	O
+0	O
+;	O
+1	O
+ml	O
+;	O
+of	O
+fetal	O
+plasma	O
+,	O
+collected	O
+during	O
+the	O
+course	O
+of	O
+normal	O
+vaginal	O
+delivery	O
+.	O
+
+In	O
+only	O
+two	O
+patients	O
+were	O
+we	O
+able	O
+to	O
+demonstrate	O
+changes	O
+suggestive	O
+of	O
+pulmonary	O
+metastases	O
+any	O
+earlier	O
+with	O
+a	O
+99mTc	O
+-	O
+EHDP	O
+scan	O
+than	O
+with	O
+chest	O
+radiographs	O
+and	O
+one	O
+of	O
+these	O
+resolved	O
+spontaneously	O
+.	O
+
+The	O
+majority	O
+of	O
+tumors	O
+occurred	O
+in	O
+the	O
+nasal	O
+cavities	O
+,	O
+although	O
+significant	O
+incidences	O
+were	O
+also	O
+found	O
+in	O
+the	O
+larynx	O
+,	O
+trachea	O
+and	O
+stem	O
+bronchi	O
+.	O
+
+Prediction	O
+of	O
+the	O
+times	O
+of	O
+sandfly	O
+development	O
+
+Native	O
+human	B-GENE
+fibrinogen	I-GENE
+was	O
+brought	O
+to	O
+coagulation	O
+by	O
+adding	O
+thrombin	B-GENE
+.	O
+
+No	O
+post	O
+-	O
+operative	O
+haemorrhages	O
+from	O
+the	O
+prostheses	O
+were	O
+observed	O
+.	O
+
+The	O
+Southern	O
+technique	O
+allowed	O
+a	O
+further	O
+localization	O
+of	O
+the	O
+region	O
+of	O
+most	O
+extensive	O
+transcription	O
+to	O
+a	O
+1	O
+.	O
+8	O
+kb	O
+HindIII	B-GENE
+-	O
+EcoRI	B-GENE
+fragment	O
+.	O
+
+Accepting	O
+arbitrarily	O
+chosen	O
+limits	O
+of	O
+maximized	O
+errors	O
+of	O
++	O
+/	O
+-	O
+10	O
+%	O
+,	O
+it	O
+could	O
+be	O
+shown	O
+that	O
+the	O
+system	O
+did	O
+not	O
+work	O
+acceptably	O
+when	O
+the	O
+mean	O
+carbon	O
+dioxide	O
+concentration	O
+was	O
+below	O
+1	O
+.	O
+5	O
+vol	O
+.	O
+%	O
+within	O
+the	O
+fresh	O
+gas	O
+flow	O
+rates	O
+(	O
+2	O
+.	O
+2	O
+-	O
+-	O
+7	O
+.	O
+7	O
+1	O
+min	O
+-	O
+1	O
+)	O
+and	O
+the	O
+range	O
+of	O
+minute	O
+ventilation	O
+(	O
+4	O
+-	O
+-	O
+10	O
+1	O
+min	O
+-	O
+1	O
+)	O
+employed	O
+.	O
+
+SV	O
+increased	O
+less	O
+in	O
+SHR	O
+,	O
+mainly	O
+reflecting	O
+the	O
+reduced	O
+diastolic	O
+compliance	O
+of	O
+the	O
+hypertrophied	O
+SHR	O
+left	O
+ventricle	O
+and	O
+the	O
+consequent	O
+rightward	O
+shift	O
+of	O
+its	O
+Frank	O
+-	O
+Starling	O
+curve	O
+.	O
+
+The	O
+carcass	O
+of	O
+a	O
+great	O
+horned	O
+owl	O
+(	O
+Bubo	O
+virginianus	O
+)	O
+,	O
+which	O
+had	O
+been	O
+found	O
+moribund	O
+in	O
+southern	O
+Ontario	O
+,	O
+was	O
+presented	O
+for	O
+necropsy	O
+.	O
+
+The	O
+inner	O
+ears	O
+were	O
+exposed	O
+by	O
+microdissection	O
+,	O
+and	O
+the	O
+vestibular	O
+sensory	O
+regions	O
+were	O
+either	O
+sectioned	O
+and	O
+studied	O
+with	O
+light	O
+or	O
+electron	O
+microscopy	O
+,	O
+or	O
+prepared	O
+and	O
+studied	O
+with	O
+the	O
+surface	O
+specimen	O
+technique	O
+.	O
+
+Patulin	O
+is	O
+extracted	O
+from	O
+apple	O
+butter	O
+samples	O
+with	O
+ethyl	O
+acetate	O
+and	O
+the	O
+extract	O
+is	O
+cleaned	O
+up	O
+on	O
+a	O
+silica	O
+gel	O
+column	O
+,	O
+using	O
+benzene	O
+-	O
+ethyl	O
+acetate	O
+(	O
+75	O
++	O
+25	O
+)	O
+as	O
+the	O
+eluant	O
+.	O
+
+Steroid	O
+glucuronides	O
+in	O
+amniotic	O
+fluid	O
+at	O
+term	O
+.	O
+
+The	O
+matrix	O
+surrounding	O
+the	O
+clusters	O
+either	O
+showed	O
+a	O
+normal	O
+morphology	O
+or	O
+a	O
+homogeneous	O
+appearance	O
+,	O
+within	O
+which	O
+faint	O
+cross	O
+striations	O
+but	O
+no	O
+distinctly	O
+fibrillar	O
+outlines	O
+could	O
+be	O
+identified	O
+.	O
+
+Riboflavin	O
+did	O
+not	O
+affect	O
+the	O
+percentage	O
+of	O
+aflatoxin	O
+-	O
+treated	O
+animals	O
+with	O
+abnormal	O
+urinary	O
+excretion	O
+patterns	O
+,	O
+but	O
+did	O
+increase	O
+the	O
+magnitude	O
+of	O
+the	O
+disturbances	O
+in	O
+elimination	O
+of	O
+kynurenic	O
+and	O
+xanthurenic	O
+acids	O
+.	O
+
+Polyglactin	O
+910	O
+suture	O
+absorption	O
+and	O
+the	O
+role	O
+of	O
+cellular	O
+enzymes	O
+.	O
+
+The	O
+incidence	O
+of	O
+DNCB	O
+reactions	O
+was	O
+78	O
+per	O
+cent	O
+for	O
+Stage	O
+I	O
+and	O
+II	O
+cancers	O
+(	O
+37	O
+patinets	O
+)	O
+,	O
+73	O
+per	O
+cent	O
+for	O
+resectable	O
+Stage	O
+III	O
+cancer	O
+(	O
+22	O
+patients	O
+)	O
+,	O
+and	O
+66	O
+per	O
+cent	O
+in	O
+patients	O
+with	O
+unresectable	O
+or	O
+inoperable	O
+Stage	O
+III	O
+cancer	O
+.	O
+
+Studies	O
+of	O
+lipoproteins	O
+should	O
+,	O
+however	O
+,	O
+be	O
+made	O
+in	O
+children	O
+from	O
+families	O
+known	O
+to	O
+have	O
+FH	O
+or	O
+early	O
+coronary	O
+heart	O
+disease	O
+.	O
+
+Sixteen	O
+other	O
+normal	O
+subjects	O
+with	O
+2	O
+g	O
+of	O
+Metyrapone	O
+are	O
+best	O
+responses	O
+.	O
+
+EEG	O
+theta	O
+waves	O
+and	O
+psychological	O
+phenomena	O
+:	O
+a	O
+review	O
+and	O
+analysis	O
+.	O
+
+REM	O
+dream	O
+content	O
+was	O
+scored	O
+for	O
+categories	O
+suggesting	O
+the	O
+predominant	O
+influence	O
+of	O
+the	O
+left	O
+hemisphere	O
+,	O
+e	O
+.	O
+g	O
+.	O
+,	O
+good	O
+ego	O
+functioning	O
+,	O
+verbalization	O
+,	O
+or	O
+the	O
+right	O
+hemisphere	O
+,	O
+e	O
+.	O
+g	O
+.	O
+,	O
+music	O
+,	O
+spatial	O
+salience	O
+,	O
+bizarreness	O
+.	O
+
+Innervation	O
+of	O
+the	O
+ventral	O
+diaphragm	O
+of	O
+the	O
+locust	O
+(	O
+Locusta	O
+migratoria	O
+)	O
+.	O
+
+Ectopic	O
+ACTH	B-GENE
+syndrome	O
+and	O
+medullary	O
+thyroid	O
+carcinoma	O
+.	O
+
+A	O
+striking	O
+finding	O
+in	O
+all	O
+of	O
+the	O
+studies	O
+was	O
+a	O
+positive	O
+correlation	O
+between	O
+PI	O
+ACTH	B-GENE
+and	O
+MSH	B-GENE
+contents	O
+.	O
+
+Chronic	O
+hypophosphatemia	O
+is	O
+the	O
+most	O
+common	O
+type	O
+of	O
+"	O
+resistant	O
+"	O
+rickets	O
+.	O
+
+There	O
+was	O
+no	O
+correlation	O
+between	O
+serum	B-GENE
+LH	I-GENE
+and	O
+chronological	O
+or	O
+bone	O
+age	O
+in	O
+this	O
+age	O
+group	O
+,	O
+which	O
+suggests	O
+that	O
+the	O
+correlation	O
+found	O
+is	O
+not	O
+due	O
+to	O
+age	O
+-	O
+related	O
+parallel	O
+phenomena	O
+.	O
+
+Molecular	O
+neurochemistry	O
+of	O
+addictive	O
+drugs	O
+.	O
+
+Efforts	O
+were	O
+made	O
+to	O
+determine	O
+the	O
+amount	O
+of	O
+time	O
+required	O
+for	O
+kidney	O
+lesions	O
+to	O
+develop	O
+and	O
+,	O
+if	O
+possible	O
+,	O
+to	O
+delineate	O
+the	O
+potential	O
+site	O
+of	O
+action	O
+of	O
+PBB	O
+.	O
+
+Effect	O
+of	O
+succimer	O
+on	O
+the	O
+intensity	O
+of	O
+tricarboxylic	B-GENE
+acid	I-GENE
+dehydrogenase	I-GENE
+reactions	O
+in	O
+the	O
+brain	O
+of	O
+rats	O
+poisoned	O
+with	O
+mercuric	O
+chloride	O
+
+Distribution	O
+and	O
+correlations	O
+of	O
+serum	O
+uric	O
+-	O
+acid	O
+in	O
+two	O
+French	O
+adult	O
+populations	O
+:	O
+13	O
+,	O
+885	O
+men	O
+and	O
+6	O
+,	O
+861	O
+women	O
+
+The	O
+incidence	O
+of	O
+hepatitis	B-GENE
+B	I-GENE
+antigen	I-GENE
+following	O
+transfusion	O
+was	O
+about	O
+2	O
+.	O
+8	O
+per	O
+cent	O
+.	O
+
+Technetium	O
+-	O
+99m	O
+stannous	O
+pyrophosphate	O
+myocardial	O
+scintigrams	O
+were	O
+obtained	O
+in	O
+138	O
+clinically	O
+stable	O
+patients	O
+32	O
+.	O
+7	O
++	O
+/	O
+-	O
+47	O
+.	O
+3	O
+weeks	O
+(	O
+range	O
+6	O
+to	O
+260	O
+)	O
+after	O
+acute	O
+myocardial	O
+infarction	O
+.	O
+
+A	O
+similar	O
+phenomenon	O
+has	O
+been	O
+reported	O
+in	O
+a	O
+few	O
+humans	O
+.	O
+
+The	O
+decline	O
+in	O
+the	O
+activity	O
+of	O
+cytochrome	B-GENE
+oxidase	I-GENE
+,	O
+peroxidase	B-GENE
+and	O
+in	O
+the	O
+lipid	O
+content	O
+of	O
+peripheral	O
+neutrophils	O
+was	O
+followed	O
+by	O
+a	O
+decrease	O
+in	O
+the	O
+phagocytic	O
+activity	O
+.	O
+
+Treatment	O
+of	O
+2	O
+patients	O
+with	O
+pseudohypoparathyroidism	O
+type	O
+I	O
+with	O
+vitamin	O
+-	O
+D	O
+-	O
+3	O
+and	O
+1	O
+alpha	O
+-	O
+Hydroxycholecalciferol	O
+consecutively	O
+resulted	O
+in	O
+a	O
+nonuniform	O
+response	O
+with	O
+regard	O
+to	O
+the	O
+normalisation	O
+of	O
+serum	O
+-	O
+calcium	O
+.	O
+
+Workers	O
+with	O
+"	O
+sensitivity	O
+"	O
+to	O
+toluene	O
+diisocyanate	O
+(	O
+TDI	O
+)	O
+studied	O
+in	O
+depth	O
+in	O
+an	O
+attempt	O
+to	O
+determine	O
+mechanisms	O
+of	O
+bronchial	O
+hyperreactivity	O
+.	O
+
+Total	O
+VO2	O
+was	O
+decreased	O
+in	O
+both	O
+groups	O
+during	O
+severe	O
+hypoxia	O
+but	O
+limb	O
+VO2	O
+was	O
+maintained	O
+in	O
+the	O
+beta	O
+-	O
+block	O
+group	O
+.	O
+beta	O
+-	O
+Block	O
+prevented	O
+the	O
+fall	O
+in	O
+total	O
+and	O
+limb	O
+peripheral	O
+resistance	O
+seen	O
+in	O
+severe	O
+hypoxia	O
+but	O
+did	O
+not	O
+alter	O
+the	O
+consistently	O
+more	O
+efficient	O
+utilization	O
+of	O
+total	O
+O2	O
+delivery	O
+shown	O
+by	O
+the	O
+limb	O
+in	O
+comparison	O
+to	O
+the	O
+whole	O
+body	O
+by	O
+higher	O
+O2	O
+extraction	O
+ratios	O
+and	O
+lower	O
+venous	O
+O2	O
+pressure	O
+.	O
+beta	B-GENE
+-	I-GENE
+Vasodilator	I-GENE
+receptors	I-GENE
+evidently	O
+played	O
+an	O
+active	O
+part	O
+in	O
+the	O
+vasodilatation	O
+seen	O
+during	O
+severe	O
+hypoxia	O
+.	O
+
+Phenobarbital	O
+-	O
+induced	O
+alterations	O
+in	O
+the	O
+metabolism	O
+of	O
+[	O
+3H	O
+]	O
+vitamin	O
+D3	O
+by	O
+the	O
+perfused	O
+rachitic	O
+rat	O
+liver	O
+in	O
+vitro	O
+.	O
+
+Modulation	O
+of	O
+25	B-GENE
+-	I-GENE
+hydroxyvitamin	I-GENE
+D3	I-GENE
+-	I-GENE
+24	I-GENE
+-	I-GENE
+hydroxylase	I-GENE
+by	O
+aminophylline	O
+:	O
+a	O
+cytochrome	B-GENE
+P	I-GENE
+-	I-GENE
+450	I-GENE
+monooxygenase	I-GENE
+system	O
+.	O
+
+In	O
+both	O
+these	O
+respects	O
+,	O
+however	O
+,	O
+the	O
+DBP	B-GENE
+mRNA	I-GENE
+resembles	O
+the	O
+late	O
+messengers	O
+of	O
+SV40	O
+and	O
+polyoma	O
+viruses	O
+.	O
+
+Effect	O
+of	O
+corticosteroid	O
+-	O
+containing	O
+antirheumatic	O
+combination	O
+drugs	O
+on	O
+endogenous	O
+ACTH	B-GENE
+and	O
+cortisol	O
+production	O
+.	O
+
+Serum	B-GENE
+ACTH	I-GENE
+did	O
+not	O
+respond	O
+to	O
+insulin	B-GENE
+and	O
+metyrapone	O
+.	O
+
+Anatomy	O
+of	O
+the	O
+RNA	O
+and	O
+gene	O
+products	O
+of	O
+MC29	O
+and	O
+MH2	O
+,	O
+two	O
+defective	O
+avian	O
+tumor	O
+viruses	O
+causing	O
+acute	O
+leukemia	O
+and	O
+carcinoma	O
+:	O
+evidence	O
+for	O
+a	O
+new	O
+class	O
+of	O
+transforming	O
+genes	O
+.	O
+
+Bertioga	O
+(	O
+Guama	O
+group	O
+)	O
+and	O
+Anhembi	O
+(	O
+Bunyamwera	O
+group	O
+)	O
+,	O
+two	O
+new	O
+arboviruses	O
+isolated	O
+in	O
+Sao	O
+Paulo	O
+,	O
+Brazil	O
+.	O
+
+Gamma	B-GENE
+glutamyl	I-GENE
+transpeptidase	I-GENE
+activity	O
+was	O
+increased	O
+up	O
+to	O
+15	O
+times	O
+above	O
+the	O
+upper	O
+normal	O
+limit	O
+in	O
+children	O
+,	O
+who	O
+received	O
+aminopyrine	O
+for	O
+two	O
+weeks	O
+or	O
+longer	O
+.	O
+
+XXI	O
+.	O
+
+A	O
+gas	O
+-	O
+liquid	O
+chromatographic	O
+method	O
+for	O
+the	O
+determination	O
+of	O
+p	O
+-	O
+chlorophenoxyisobutyric	O
+(	O
+CPIB	O
+)	O
+acid	O
+in	O
+blood	O
+plasma	O
+is	O
+described	O
+.	O
+
+Dopamine	B-GENE
+receptor	I-GENE
+blockade	O
+and	O
+the	O
+neuroleptics	O
+,	O
+a	O
+crystallographic	O
+study	O
+.	O
+
+V	O
+.	O
+
+A	O
+rapid	O
+fluorimetric	O
+procedure	O
+for	O
+the	O
+determination	O
+of	O
+the	O
+fungicide	O
+5	O
+-	O
+fluorocytosine	O
+in	O
+serum	O
+is	O
+described	O
+.	O
+
+The	O
+'	O
+field	O
+of	O
+stress	O
+'	O
+of	O
+the	O
+supervisory	O
+nurse	O
+
+How	O
+do	O
+graduates	O
+of	O
+different	O
+types	O
+of	O
+programs	O
+perform	O
+on	O
+state	O
+boards	O
+?	O
+
+Similarly	O
+,	O
+maternal	B-GENE
+serum	I-GENE
+somatomedin	I-GENE
+A	I-GENE
+was	O
+significantly	O
+reduced	O
+in	O
+rats	O
+nursing	O
+large	O
+litters	O
+.	O
+
+The	O
+sequences	O
+following	O
+the	O
+X	O
+.	O
+borealis	O
+oocyte	O
+and	O
+somatic	O
+5S	B-GENE
+genes	I-GENE
+are	O
+identical	O
+in	O
+12	O
+of	O
+the	O
+first	O
+14	O
+residues	O
+and	O
+contain	O
+two	O
+or	O
+more	O
+T	O
+clusters	O
+,	O
+as	O
+does	O
+the	O
+corresponding	O
+region	O
+of	O
+X	B-GENE
+.	I-GENE
+laevis	I-GENE
+oocyte	I-GENE
+5S	I-GENE
+DNA	I-GENE
+.	O
+
+This	O
+mechanism	O
+is	O
+not	O
+due	O
+to	O
+the	O
+observed	O
+grain	O
+boundary	O
+precipitates	O
+.	O
+
+This	O
+report	O
+has	O
+reviewed	O
+some	O
+of	O
+the	O
+reasons	O
+for	O
+treatment	O
+failures	O
+and	O
+has	O
+presented	O
+a	O
+philosophy	O
+for	O
+their	O
+management	O
+.	O
+
+Diagnosis	O
+and	O
+treatment	O
+planning	O
+in	O
+Class	O
+II	O
+,	O
+division	O
+2	O
+
+Because	O
+of	O
+serious	O
+infections	O
+(	O
+fever	O
+larger	O
+than	O
+or	O
+equal	O
+to	O
+101	O
+degrees	O
+F	O
+.	O
+granulocytes	O
+less	O
+than	O
+1	O
+,	O
+000	O
+/	O
+mm	O
+,	O
+3	O
+and	O
+hospitalization	O
+)	O
+and	O
+1	O
+drug	O
+death	O
+in	O
+the	O
+first	O
+4	O
+patients	O
+,	O
+oral	O
+calcium	O
+leucovorin	O
+,	O
+20	O
+to	O
+30	O
+mg	O
+/	O
+m2	O
+orally	O
+,	O
+was	O
+given	O
+2	O
+days	O
+after	O
+methotrexate	O
+in	O
+subsequent	O
+treatment	O
+cycles	O
+.	O
+
+It	O
+seems	O
+that	O
+the	O
+way	O
+in	O
+which	O
+drugs	O
+modify	O
+a	O
+patient	O
+'	O
+s	O
+serum	O
+chemistry	O
+may	O
+be	O
+used	O
+to	O
+assess	O
+the	O
+efficacy	O
+with	O
+which	O
+they	O
+control	O
+the	O
+inflammatory	O
+process	O
+.	O
+
+Here	O
+the	O
+conventional	O
+tests	O
+clearly	O
+pointed	O
+to	O
+the	O
+presence	O
+of	O
+retrocochlear	O
+disease	O
+.	O
+
+The	O
+end	O
+-	O
+stage	O
+or	O
+involutional	O
+phase	O
+of	O
+proliferative	O
+diabetic	O
+retinopathy	O
+may	O
+result	O
+in	O
+stabilization	O
+of	O
+vision	O
+for	O
+long	O
+periods	O
+of	O
+time	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+serum	B-GENE
+alpha1AT	I-GENE
+quantitation	O
+,	O
+newborn	O
+infants	O
+may	O
+be	O
+separated	O
+into	O
+two	O
+groups	O
+,	O
+characterized	O
+respectively	O
+by	O
+concentrations	O
+above	O
+or	O
+below	O
+150	O
+mg	O
+%	O
+.	O
+
+In	O
+patients	O
+who	O
+were	O
+not	O
+vented	O
+,	O
+there	O
+was	O
+overall	O
+significant	O
+depression	O
+of	O
+function	O
+(	O
+67	O
++	O
+/	O
+-	O
+5	O
+%	O
+of	O
+control	O
+;	O
+range	O
+,	O
+91	O
+-	O
+-	O
+45	O
+%	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Changes	O
+in	O
+body	O
+weight	O
+and	O
+agonistic	O
+behavior	O
+were	O
+also	O
+recorded	O
+.	O
+
+The	O
+uterine	O
+response	O
+to	O
+prostaglandin	O
+E2	O
+(	O
+PGE2	O
+)	O
+and	O
+prostaglandin	O
+F2alpha	O
+(	O
+administered	O
+by	O
+intravenous	O
+and	O
+intrauterine	O
+routes	O
+)	O
+was	O
+evaluated	O
+during	O
+different	O
+phases	O
+of	O
+the	O
+menstrual	O
+cycle	O
+in	O
+five	O
+functionally	O
+infertile	O
+women	O
+.	O
+
+A	O
+total	O
+of	O
+26	O
+BCG	O
+strains	O
+,	O
+out	O
+of	O
+them	O
+10	O
+Czechoslovak	O
+strains	O
+(	O
+2	O
+lyophilized	O
+cultures	O
+of	O
+BCG	O
+of	O
+different	O
+batch	O
+,	O
+6	O
+strains	O
+isolated	O
+from	O
+abscesses	O
+of	O
+children	O
+after	O
+BCG	O
+-	O
+vaccination	O
+and	O
+2	O
+strains	O
+from	O
+fatal	O
+cases	O
+after	O
+BCG	O
+-	O
+vaccination	O
+)	O
+and	O
+16	O
+strains	O
+obtained	O
+from	O
+foreign	O
+laboratories	O
+,	O
+were	O
+used	O
+.	O
+
+High	O
+levels	O
+of	O
+serum	O
+calcitonin	B-GENE
+were	O
+found	O
+in	O
+patients	O
+with	O
+chronic	O
+renal	O
+failure	O
+.	O
+
+Detection	O
+of	O
+anti	O
+-	O
+lymphocyte	O
+antibodies	O
+using	O
+the	O
+immunoperoxidase	B-GENE
+antiglobulin	B-GENE
+technic	O
+.	O
+
+The	O
+response	O
+of	O
+serum	B-GENE
+GH	I-GENE
+to	O
+arginine	O
+infusion	O
+was	O
+normal	O
+,	O
+while	O
+that	O
+to	O
+insulin	B-GENE
+-	O
+induced	O
+hypoglycemia	O
+was	O
+poor	O
+.	O
+
+The	O
+mortality	O
+rate	O
+and	O
+histopathological	O
+features	O
+of	O
+Nocardia	O
+asteroides	O
+and	O
+Nocardia	O
+brasiliensis	O
+infections	O
+in	O
+congenitally	O
+athymic	O
+(	O
+nude	O
+)	O
+mice	O
+of	O
+ICR	O
+and	O
+C3H	O
+/	O
+eB	O
+origins	O
+were	O
+quite	O
+different	O
+from	O
+what	O
+we	O
+found	O
+for	O
+Swiss	O
+white	O
+mice	O
+and	O
+other	O
+inbred	O
+mouse	O
+strains	O
+(	O
+namely	O
+,	O
+C57	O
+/	O
+BL	O
+/	O
+6J	O
+,	O
+New	O
+Zealand	O
+Black	O
+,	O
+BALB	O
+/	O
+c	O
+,	O
+CBA	O
+/	O
+LAC	O
+,	O
+and	O
+C3H	O
+/	O
+eB	O
+)	O
+.	O
+
+Williams	O
+,	O
+2	O
+August	O
+1977	O
+.	O
+
+Use	O
+of	O
+radioactive	O
+isotopes	O
+in	O
+the	O
+chemistry	O
+of	O
+proteins	O
+
+(	O
+Emeritus	O
+)	O
+John	O
+Henri	O
+Roosegaarde	O
+Bisschop	O
+
+Disrupted	O
+vaccines	O
+and	O
+whole	O
+-	O
+virus	O
+vaccines	O
+containing	O
+type	B-GENE
+B	I-GENE
+antigen	I-GENE
+only	O
+did	O
+not	O
+cause	O
+significant	O
+reactivity	O
+.	O
+
+255	O
+-	O
+61	O
+.	O
+
+Antenatal	O
+diagnosis	O
+of	O
+haematological	O
+disorders	O
+-	O
+-	O
+'	O
+1978	O
+'	O
+.	O
+
+Hepatic	O
+oxygen	O
+supply	O
+and	O
+selected	O
+blood	O
+parameters	O
+were	O
+recorded	O
+in	O
+fasted	O
+male	O
+rates	O
+given	O
+20	O
+-	O
+-	O
+30	O
+mg	O
+/	O
+kg	O
+Escherichia	B-GENE
+coli	I-GENE
+endotoxin	I-GENE
+intraperitoneally	O
+.	O
+
+Gonadal	O
+dysfunction	O
+in	O
+patients	O
+with	O
+ataxia	O
+telangiectasia	O
+.	O
+
+The	O
+maximum	O
+period	O
+of	O
+treatment	O
+was	O
+73	O
+(	O
+oral	O
+)	O
+,	O
+73	O
+(	O
+intraperitoneal	O
+)	O
+or	O
+75	O
+(	O
+dermal	O
+)	O
+weeks	O
+.	O
+
+A	O
+study	O
+of	O
+the	O
+comparative	O
+efficacy	O
+of	O
+diflucortolone	O
+valerate	O
+0	O
+.	O
+3	O
+%	O
+ointment	O
+and	O
+clobetasol	O
+propionate	O
+0	O
+.	O
+05	O
+%	O
+ointment	O
+.	O
+
+Most	O
+of	O
+the	O
+phenomena	O
+of	O
+azotaemic	O
+osteodystrophy	O
+are	O
+encountered	O
+in	O
+simple	O
+vitamin	O
+D	O
+deficiency	O
+;	O
+as	O
+in	O
+that	O
+condition	O
+,	O
+deficiency	O
+of	O
+1	O
+,	O
+25	O
+-	O
+dihydroxycholecalciferol	O
+may	O
+be	O
+of	O
+primary	O
+significance	O
+in	O
+causing	O
+secondary	O
+hyperparathyroidism	O
+in	O
+renal	O
+failure	O
+.	O
+
+Basal	O
+FSH	B-GENE
+and	O
+LH	B-GENE
+levels	O
+were	O
+significantly	O
+lower	O
+in	O
+addicts	O
+;	O
+after	O
+GnRH	B-GENE
+stimulation	O
+the	O
+addicts	O
+'	O
+FSH	B-GENE
+and	O
+LH	B-GENE
+values	O
+increased	O
+but	O
+not	O
+significantly	O
+compared	O
+to	O
+controls	O
+.	O
+
+Adriamycin	O
+:	O
+comparison	O
+of	O
+a	O
+5	O
+-	O
+week	O
+schedule	O
+with	O
+a	O
+3	O
+-	O
+week	O
+schedule	O
+in	O
+the	O
+treatment	O
+of	O
+breast	O
+cancer	O
+.	O
+
+Follow	O
+-	O
+up	O
+controls	O
+of	O
+luteinizing	B-GENE
+hormone	I-GENE
+(	O
+LH	B-GENE
+)	O
+,	O
+follicle	B-GENE
+stimulating	I-GENE
+hormone	I-GENE
+(	O
+FSH	B-GENE
+)	O
+,	O
+prolactin	B-GENE
+(	O
+HPRL	B-GENE
+)	O
+,	O
+oestradiol	O
+(	O
+E2	O
+)	O
+,	O
+progesterone	O
+(	O
+P	O
+)	O
+and	O
+testosterone	O
+(	O
+T	O
+)	O
+in	O
+the	O
+catabolic	O
+and	O
+healing	O
+phase	O
+of	O
+burn	O
+disease	O
+.	O
+
+Renin	B-GENE
+studies	O
+performed	O
+in	O
+34	O
+hypertensive	O
+patients	O
+and	O
+in	O
+a	O
+control	O
+group	O
+of	O
+11	O
+recipients	O
+showed	O
+that	O
+elevation	O
+of	O
+plasma	B-GENE
+renin	I-GENE
+activity	O
+and	O
+of	O
+plasma	O
+aldosterone	O
+level	O
+is	O
+frequent	O
+but	O
+difficult	O
+to	O
+interpret	O
+,	O
+particularly	O
+when	O
+a	O
+renal	O
+artery	O
+stenosis	O
+is	O
+observed	O
+.	O
+
+A	O
+randomized	O
+clinical	O
+trial	O
+in	O
+sixty	O
+-	O
+two	O
+adult	O
+patients	O
+suffering	O
+from	O
+typhoid	O
+fever	O
+,	O
+proved	O
+by	O
+blood	O
+and	O
+marrow	O
+culture	O
+,	O
+showed	O
+that	O
+amoxycillin	O
+in	O
+a	O
+dosage	O
+schedule	O
+of	O
+1	O
+g	O
+8	O
+-	O
+hourly	O
+orally	O
+for	O
+fourteen	O
+days	O
+was	O
+better	O
+than	O
+chloramphenicol	O
+with	O
+regard	O
+to	O
+clinical	O
+and	O
+temperature	O
+response	O
+and	O
+in	O
+respect	O
+of	O
+carriers	O
+and	O
+relapse	O
+rates	O
+.	O
+
+202	O
+-	O
+8	O
+.	O
+
+Bone	O
+marrow	O
+transplantation	O
+-	O
+1979	O
+.	O
+
+In	O
+this	O
+article	O
+,	O
+the	O
+clinical	O
+actions	O
+of	O
+the	O
+principal	O
+dopamine	B-GENE
+receptor	I-GENE
+stimulating	O
+agents	O
+(	O
+apomorphine	O
+and	O
+its	O
+derivatives	O
+;	O
+piribedil	O
+,	O
+rye	O
+-	O
+ergot	O
+derivatives	O
+)	O
+are	O
+discussed	O
+on	O
+the	O
+basis	O
+of	O
+their	O
+biochemical	O
+and	O
+pharmacological	O
+properties	O
+.	O
+
+The	O
+unilateral	O
+vestibular	O
+hypofunction	O
+.	O
+
+Thus	O
+,	O
+the	O
+inhibition	O
+of	O
+pepsin	B-GENE
+in	O
+human	O
+gastric	O
+juice	O
+does	O
+not	O
+appear	O
+to	O
+have	O
+a	O
+major	O
+influence	O
+on	O
+the	O
+healing	O
+of	O
+duodenal	O
+ulcer	O
+.	O
+
+The	O
+IDF	O
+standard	O
+method	O
+for	O
+the	O
+detection	O
+of	O
+penicillin	O
+in	O
+milk	O
+is	O
+not	O
+suitable	O
+for	O
+the	O
+detection	O
+of	O
+sulphonamide	O
+residues	O
+in	O
+milk	O
+.	O
+
+Capsular	O
+antigens	O
+of	O
+Staphylococcus	O
+aureus	O
+
+The	O
+course	O
+of	O
+endotoxin	O
+fever	O
+remained	O
+uninfluenced	O
+by	O
+ALS	O
+.	O
+
+2	O
+new	O
+Algerian	O
+cases	O
+
+Seventy	O
+-	O
+one	O
+percent	O
+of	O
+patients	O
+treated	O
+with	O
+ticarcillin	O
+alone	O
+responded	O
+favorably	O
+.	O
+
+Accurate	O
+pathologic	O
+staging	O
+identifies	O
+patients	O
+who	O
+are	O
+potentially	O
+curable	O
+with	O
+radiotherapy	O
+.	O
+
+Inherent	O
+hematology	O
+of	O
+old	O
+age	O
+
+Neomycin	O
+is	O
+fairly	O
+effective	O
+against	O
+staphylococci	O
+,	O
+less	O
+effective	O
+against	O
+streptococci	O
+,	O
+and	O
+fairly	O
+effective	O
+against	O
+gram	O
+-	O
+negative	O
+intestinal	O
+organisms	O
+.	O
+
+It	O
+was	O
+concluded	O
+,	O
+that	O
+on	O
+a	O
+given	O
+section	O
+,	O
+75	O
+,	O
+7	O
+per	O
+cent	O
+of	O
+the	O
+trabeculae	O
+were	O
+in	O
+contact	O
+with	O
+vascular	O
+cavities	O
+.	O
+
+2	O
+.	O
+
+Changes	O
+in	O
+tissue	O
+PCO2	O
+were	O
+less	O
+dramatic	O
+and	O
+did	O
+not	O
+vary	O
+significantly	O
+from	O
+those	O
+recorded	O
+in	O
+venous	O
+blood	O
+.	O
+
+Ultrasonic	O
+evaluation	O
+of	O
+renal	O
+calculi	O
+.	O
+
+Recognition	O
+of	O
+emphysema	O
+was	O
+poor	O
+when	O
+radiographs	O
+of	O
+inadequate	O
+quality	O
+were	O
+included	O
+(	O
+anteroposterior	O
+films	O
+or	O
+films	O
+from	O
+patients	O
+with	O
+acute	O
+or	O
+chronic	O
+lung	O
+disease	O
+)	O
+.	O
+
+Isolation	O
+of	O
+T	O
+.	O
+gambiense	O
+strains	O
+in	O
+Zaire	O
+and	O
+their	O
+adaptation	O
+to	O
+laboratory	O
+animals	O
+
+Pharmacokinetic	O
+profile	O
+of	O
+clonazepam	O
+in	O
+rhesus	O
+monkeys	O
+.	O
+
+Immunologic	O
+mechanisms	O
+in	O
+chronic	O
+brucellosis	O
+in	O
+humans	O
+.	O
+
+Intestinal	O
+adaptation	O
+(	O
+first	O
+of	O
+two	O
+parts	O
+)	O
+.	O
+
+In	O
+patients	O
+who	O
+had	O
+received	O
+no	O
+previous	O
+drug	O
+treatment	O
+,	O
+log	O
+baseline	O
+plasma	B-GENE
+renin	I-GENE
+activity	O
+and	O
+change	O
+in	O
+mean	O
+blood	O
+pressure	O
+after	O
+SQ	O
+20881	O
+correlated	O
+significantly	O
+(	O
+r	O
+=	O
+0	O
+.	O
+651	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+These	O
+techniques	O
+have	O
+been	O
+used	O
+by	O
+many	O
+people	O
+for	O
+many	O
+years	O
+and	O
+no	O
+claim	O
+is	O
+being	O
+made	O
+for	O
+any	O
+innovation	O
+in	O
+this	O
+regard	O
+.	O
+
+40	O
+patients	O
+with	O
+chronic	O
+osteomyelitis	O
+were	O
+treated	O
+per	O
+os	O
+with	O
+the	O
+bactericidal	O
+beta	O
+-	O
+lactam	O
+-	O
+antibiotic	O
+cephalexin	O
+during	O
+3	O
+to	O
+60	O
+weeks	O
+.	O
+
+A	O
+total	O
+of	O
+57	O
+patients	O
+with	O
+Hodgkin	O
+'	O
+s	O
+disease	O
+limited	O
+to	O
+above	O
+the	O
+diaphragm	O
+(	O
+Stages	O
+I	O
+and	O
+II	O
+,	O
+A	O
+and	O
+B	O
+)	O
+were	O
+treated	O
+with	O
+radiation	O
+therapy	O
+alone	O
+at	O
+the	O
+University	O
+of	O
+Florida	O
+between	O
+1964	O
+and	O
+1974	O
+.	O
+
+Year	O
+one	O
+of	O
+the	O
+first	O
+general	O
+practitioner	O
+medical	O
+unit	O
+in	O
+the	O
+greater	O
+Glasgow	O
+area	O
+.	O
+
+This	O
+multiple	O
+-	O
+electrode	O
+array	O
+for	O
+round	O
+window	O
+cochlear	O
+implantation	O
+is	O
+a	O
+robust	O
+,	O
+reliable	O
+system	O
+for	O
+inserting	O
+20	O
+mm	O
+along	O
+the	O
+scala	O
+tympani	O
+with	O
+a	O
+minimum	O
+of	O
+trauma	O
+and	O
+can	O
+provide	O
+for	O
+bipolar	O
+stimulation	O
+.	O
+
+As	O
+authorized	O
+by	O
+the	O
+World	O
+Health	O
+Organization	O
+29th	O
+Expert	O
+Committee	O
+on	O
+Biological	O
+Standardization	O
+,	O
+the	O
+preparation	O
+of	O
+human	B-GENE
+prolactin	I-GENE
+in	O
+ampoules	O
+coded	O
+75	O
+/	O
+504	O
+has	O
+been	O
+established	O
+as	O
+the	O
+International	O
+Reference	O
+Preparation	O
+(	O
+IRP	O
+)	O
+of	O
+human	B-GENE
+prolactin	I-GENE
+for	O
+immunoassay	O
+.	O
+
+i	O
+.	O
+
+Biliary	O
+-	O
+enteric	O
+fistulas	O
+
+Plasma	O
+ion	O
+changes	O
+in	O
+venous	O
+blood	O
+incubated	O
+with	O
+beta	B-GENE
+receptor	I-GENE
+blockers	O
+and	O
+subjected	O
+to	O
+tonometry	O
+in	O
+vitro	O
+.	O
+
+Such	O
+marked	O
+differences	O
+are	O
+found	O
+occasionally	O
+in	O
+the	O
+literature	O
+:	O
+heterophile	O
+antibodies	O
+against	O
+bovine	B-GENE
+gammaglobulin	I-GENE
+are	O
+regarded	O
+as	O
+responsible	O
+for	O
+the	O
+interference	O
+in	O
+the	O
+Sephadex	O
+system	O
+of	O
+RIST	O
+.	O
+
+"	O
+Let	O
+the	O
+hundred	O
+flowers	O
+bloom	O
+"	O
+.	O
+
+Various	O
+treatment	O
+modalities	O
+are	O
+reviewed	O
+in	O
+the	O
+context	O
+of	O
+the	O
+psychology	O
+as	O
+well	O
+as	O
+the	O
+physiology	O
+of	O
+severe	O
+intractable	O
+pain	O
+.	O
+
+Lethal	O
+Tachmalcor	O
+(	O
+4	O
+-	O
+(	O
+3	O
+'	O
+-	O
+diethylamino	O
+-	O
+2	O
+'	O
+-	O
+hydroxypropyl	O
+)	O
+-	O
+ajmaline	O
+)	O
+poisoning	O
+in	O
+childhood	O
+
+Ophthalmosonographic	O
+evaluation	O
+of	O
+blood	O
+flow	O
+velocity	O
+in	O
+arteriocavernous	O
+fistula	O
+
+Serum	O
+ferritin	B-GENE
+concentration	O
+and	O
+bone	O
+marrow	O
+iron	O
+stores	O
+.	O
+
+The	O
+systolic	O
+pressure	O
+gradient	O
+(	O
+SPG	O
+)	O
+between	O
+the	O
+left	O
+ventricle	O
+(	O
+LV	O
+)	O
+and	O
+left	O
+atrium	O
+(	O
+LA	O
+)	O
+was	O
+obtained	O
+from	O
+high	O
+-	O
+fidelity	O
+pressure	O
+transducers	O
+.	O
+
+A	O
+prospective	O
+trail	O
+comparing	O
+hysterectomy	O
+,	O
+hysterectomy	O
+plus	O
+vaginal	O
+radium	O
+,	O
+and	O
+uterine	O
+radium	O
+plus	O
+hysterectomy	O
+in	O
+stage	O
+I	O
+endometrial	O
+carcinoma	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+a	O
+patient	O
+'	O
+s	O
+report	O
+of	O
+one	O
+inaccurate	O
+Clinitemp	O
+,	O
+we	O
+undertook	O
+to	O
+investigate	O
+the	O
+accuracy	O
+of	O
+this	O
+thermometer	O
+.	O
+
+Cryoglobulinemia	O
+in	O
+Raynaud	O
+'	O
+s	O
+syndrome	O
+
+Data	O
+were	O
+processed	O
+with	O
+a	O
+semi	O
+-	O
+automatic	O
+computer	O
+program	O
+which	O
+develops	O
+an	O
+averaged	O
+-	O
+volume	O
+curve	O
+from	O
+an	O
+assigned	O
+LV	O
+region	O
+-	O
+of	O
+-	O
+interest	O
+.	O
+
+The	O
+preferential	O
+serum	B-GENE
+IgA	I-GENE
+response	O
+observed	O
+in	O
+the	O
+patient	O
+population	O
+suggests	O
+that	O
+bronchial	O
+associated	O
+lymphoid	O
+tissue	O
+in	O
+the	O
+diseased	O
+lung	O
+is	O
+an	O
+important	O
+source	O
+of	O
+circulating	O
+IgA	B-GENE
+.	O
+
+Ultimate	O
+strengthes	O
+seem	O
+to	O
+be	O
+reached	O
+for	O
+cast	O
+cobalt	O
+alloys	O
+,	O
+whereas	O
+titanium	O
+alloys	O
+,	O
+such	O
+as	O
+Ta	O
+6	O
+V	O
+,	O
+present	O
+very	O
+high	O
+fatigue	O
+limit	O
+under	O
+corrosion	O
+.	O
+
+The	O
+effects	O
+of	O
+intracisternal	O
+injection	O
+(	O
+i	O
+.	O
+c	O
+.	O
+i	O
+.	O
+)	O
+of	O
+clonidine	O
+(	O
+1	O
+microgram	O
+kg	O
+-	O
+1	O
+)	O
+on	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+were	O
+studied	O
+in	O
+conscious	O
+rabbits	O
+with	O
+an	O
+implanted	O
+catheter	O
+in	O
+the	O
+cisterna	O
+magna	O
+.	O
+
+Platelet	O
+number	O
+and	O
+life	O
+span	O
+were	O
+determined	O
+in	O
+the	O
+last	O
+trimester	O
+of	O
+pregnancy	O
+in	O
+22	O
+women	O
+who	O
+were	O
+delivered	O
+of	O
+small	O
+-	O
+for	O
+-	O
+gestational	O
+age	O
+(	O
+SGA	O
+)	O
+infants	O
+and	O
+in	O
+21	O
+women	O
+with	O
+infants	O
+having	O
+normal	O
+birth	O
+weights	O
+.	O
+
+Serial	O
+measurements	O
+of	O
+total	O
+serum	O
+IgE	B-GENE
+appears	O
+to	O
+be	O
+a	O
+useful	O
+index	O
+of	O
+disease	O
+activity	O
+in	O
+ABPA	O
+.	O
+
+A	O
+rise	O
+of	O
+hemoglobin	B-GENE
+concentration	O
+accompanied	O
+by	O
+an	O
+increase	O
+of	O
+the	O
+total	O
+iron	O
+in	O
+the	O
+blood	O
+serum	O
+of	O
+white	O
+mice	O
+was	O
+found	O
+under	O
+oxygen	O
+pressure	O
+of	O
+4	O
+atm	O
+for	O
+an	O
+hour	O
+(	O
+preconvulsive	O
+state	O
+)	O
+and	O
+6	O
+atm	O
+(	O
+convulsive	O
+state	O
+)	O
+.	O
+
+Nernst	O
+-	O
+-	O
+Planck	O
+analog	O
+equations	O
+and	O
+stationary	O
+state	O
+membrane	O
+electric	O
+potentials	O
+.	O
+
+Effects	O
+of	O
+methylene	O
+chloride	O
+,	O
+trichloroethane	O
+,	O
+trichloroethylene	O
+,	O
+tetrachloroethylene	O
+and	O
+toluene	O
+on	O
+the	O
+development	O
+of	O
+chick	O
+embryos	O
+.	O
+
+Effect	O
+of	O
+intraventricular	O
+administration	O
+of	O
+streptolysin	B-GENE
+O	I-GENE
+on	O
+the	O
+electroencephalogram	O
+of	O
+rabbits	O
+.	O
+
+In	O
+this	O
+situation	O
+the	O
+convlusion	O
+threshold	O
+for	O
+the	O
+8	O
+substances	O
+is	O
+as	O
+follows	O
+:	O
+pethidine	O
+20	O
+mg	O
+.	O
+kg	O
+-	O
+1	O
+I	O
+.	O
+V	O
+.	O
+,	O
+piritramide	O
+30	O
+,	O
+morphine	O
+180	O
+,	O
+phenoperidine	O
+4	O
+,	O
+R	O
+39	O
+209	O
+5	O
+,	O
+fentanyl	O
+4	O
+,	O
+sufentanil	O
+4	O
+and	O
+R	O
+34	O
+995	O
+10	O
+mg	O
+.	O
+kg	O
+-	O
+1	O
+I	O
+.	O
+V	O
+.	O
+
+Roentgenographically	O
+,	O
+the	O
+lesion	O
+was	O
+usually	O
+a	O
+well	O
+-	O
+defined	O
+and	O
+benign	O
+appearing	O
+one	O
+,	O
+either	O
+purely	O
+lytic	O
+(	O
+3	O
+cases	O
+)	O
+or	O
+with	O
+central	O
+radiodensity	O
+(	O
+2	O
+cases	O
+)	O
+.	O
+
+Effects	O
+of	O
+chronic	O
+descending	O
+tractotomy	O
+on	O
+the	O
+response	O
+patterns	O
+of	O
+neurons	O
+in	O
+the	O
+trigeminal	O
+nuclei	O
+principalis	O
+and	O
+oralis	O
+.	O
+
+Efficacy	O
+of	O
+a	O
+three	O
+-	O
+versus	O
+a	O
+five	O
+-	O
+week	O
+alcohol	O
+treatment	O
+program	O
+.	O
+
+Isolated	O
+calcaneal	O
+tuberculous	O
+osteomyelitis	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+opiate	B-GENE
+receptors	I-GENE
+bordering	O
+the	O
+fourth	O
+cerebral	O
+ventricle	O
+mediate	O
+the	O
+cardiovascular	O
+and	O
+hypnotic	O
+action	O
+of	O
+fentanyl	O
+.	O
+
+In	O
+case	O
+of	O
+a	O
+pathologically	O
+convoluted	O
+internal	O
+carotid	O
+the	O
+common	O
+carotid	O
+artery	O
+was	O
+resected	O
+with	O
+an	O
+end	O
+-	O
+to	O
+-	O
+end	O
+anastomosis	O
+.	O
+
+These	O
+data	O
+confirm	O
+the	O
+existence	O
+of	O
+hyperlipemic	O
+abdominal	O
+crisis	O
+as	O
+a	O
+distinct	O
+entity	O
+and	O
+testify	O
+to	O
+the	O
+importance	O
+of	O
+recognizing	O
+this	O
+syndrome	O
+in	O
+order	O
+to	O
+avoid	O
+the	O
+occurrence	O
+of	O
+acute	O
+pancreatitis	O
+and	O
+the	O
+performance	O
+of	O
+unnecessary	O
+and	O
+potentially	O
+harmful	O
+surgery	O
+.	O
+
+In	O
+addition	O
+a	O
+significant	O
+Treatment	O
+X	O
+Strain	O
+interaction	O
+was	O
+due	O
+to	O
+the	O
+larger	O
+defecation	O
+numbers	O
+displayed	O
+by	O
+the	O
+taurine	O
+-	O
+injected	O
+MR	O
+rats	O
+relative	O
+to	O
+the	O
+saline	O
+-	O
+injected	O
+MR	O
+rats	O
+.	O
+
+The	O
+failures	O
+frequently	O
+were	O
+related	O
+to	O
+patient	O
+intolerance	O
+or	O
+poor	O
+mechanical	O
+fit	O
+and	O
+occurred	O
+in	O
+the	O
+first	O
+few	O
+days	O
+or	O
+first	O
+few	O
+months	O
+after	O
+insertion	O
+.	O
+
+These	O
+characteristics	O
+indicated	O
+the	O
+pronounced	O
+activity	O
+of	O
+collagenous	O
+fiber	O
+synthesis	O
+and	O
+the	O
+matrix	O
+of	O
+the	O
+osteoid	O
+tissue	O
+.	O
+
+Carbohydrate	O
+metabolism	O
+and	O
+the	O
+semen	O
+profile	O
+:	O
+glucose	O
+,	O
+insulin	B-GENE
+,	O
+and	O
+sperm	O
+studies	O
+.	O
+
+It	O
+has	O
+come	O
+out	O
+that	O
+CAEC	O
+is	O
+between	O
+CC	O
+and	O
+CIEC	O
+and	O
+that	O
+attacks	O
+of	O
+biliary	O
+fever	O
+and	O
+high	O
+levels	O
+of	O
+alkaline	B-GENE
+phosphatase	I-GENE
+and	O
+transaminases	O
+in	O
+the	O
+serum	O
+are	O
+the	O
+helpful	O
+findings	O
+for	O
+preoperative	O
+diagnosis	O
+.	O
+
+The	O
+sub	O
+-	O
+acute	O
+inhalation	O
+toxicity	O
+of	O
+furfural	O
+was	O
+studied	O
+in	O
+Syrian	O
+golden	O
+hamsters	O
+.	O
+
+A	O
+study	O
+of	O
+the	O
+E	O
+.	O
+O	O
+.	O
+R	O
+.	O
+T	O
+.	O
+C	O
+.	O
+
+An	O
+intravenous	O
+preparation	O
+of	O
+doxycycline	O
+(	O
+DOTC	O
+,	O
+Vibramycin	O
+'	O
+Pfizer	O
+'	O
+)	O
+,	O
+a	O
+long	O
+-	O
+lasting	O
+tetracycline	O
+,	O
+was	O
+administered	O
+mainly	O
+by	O
+drip	O
+infusion	O
+for	O
+a	O
+series	O
+of	O
+study	O
+in	O
+the	O
+pediatrics	O
+field	O
+,	O
+and	O
+the	O
+results	O
+were	O
+as	O
+follows	O
+:	O
+1	O
+)	O
+DOTC	O
+(	O
+100	O
+mg	O
+)	O
+was	O
+dissolved	O
+in	O
+a	O
+100	O
+ml	O
+of	O
+glucose	O
+solution	O
+and	O
+2	O
+-	O
+-	O
+3	O
+mg	O
+/	O
+kg	O
+was	O
+administered	O
+intravenously	O
+.	O
+
+5	O
+)	O
+Before	O
+and	O
+ten	O
+days	O
+after	O
+DOTC	O
+infusion	O
+,	O
+laboratory	O
+tests	O
+for	O
+liver	O
+and	O
+renal	O
+functions	O
+and	O
+blood	O
+were	O
+performed	O
+.	O
+
+Structural	O
+characteristics	O
+of	O
+the	O
+erythrocyte	O
+membrane	O
+,	O
+peroxidation	O
+processes	O
+and	O
+antioxidant	O
+function	O
+in	O
+children	O
+with	O
+diffuse	O
+glomerulonephritis	O
+
+The	O
+enteric	O
+route	O
+is	O
+the	O
+principal	O
+mode	O
+of	O
+transmission	O
+for	O
+hepatitis	O
+A	O
+,	O
+but	O
+maximal	O
+levels	O
+of	O
+hepatitis	O
+A	O
+virus	O
+excretion	O
+occur	O
+before	O
+the	O
+onset	O
+of	O
+jaundice	O
+.	O
+
+All	O
+13	O
+patients	O
+showed	O
+endoscopic	O
+evidence	O
+of	O
+oesophagitis	O
+,	O
+moderate	O
+in	O
+4	O
+and	O
+severe	O
+in	O
+9	O
+.	O
+
+Urinary	O
+excretion	O
+of	O
+oestrone	O
+,	O
+oestradiol	O
+-	O
+17	O
+beta	O
+and	O
+oestriol	O
+in	O
+pregnancies	O
+complicated	O
+by	O
+steroid	B-GENE
+sulphatase	I-GENE
+deficiency	O
+.	O
+
+Both	O
+reduced	O
+spontaneous	O
+locomotor	O
+activity	O
+in	O
+mice	O
+,	O
+protected	O
+them	O
+from	O
+death	O
+from	O
+amphetamine	O
+induced	O
+toxicity	O
+,	O
+prolonged	O
+hexobarbitone	O
+sleeping	O
+time	O
+and	O
+caused	O
+a	O
+depletion	O
+of	O
+catecholamines	O
+from	O
+various	O
+organs	O
+of	O
+the	O
+rat	O
+.	O
+
+On	O
+the	O
+role	O
+of	O
+transferrin	B-GENE
+in	O
+the	O
+uptake	O
+of	O
+gallium	O
+by	O
+tumor	O
+cells	O
+.	O
+
+Irradiation	O
+of	O
+human	O
+blood	O
+platelets	O
+with	O
+UV	O
+-	O
+A	O
+in	O
+vitro	O
+impairs	O
+their	O
+ability	O
+to	O
+aggregate	O
+after	O
+challenge	O
+with	O
+collagen	B-GENE
+.	O
+
+Following	O
+the	O
+satisfactory	O
+results	O
+and	O
+taking	O
+into	O
+account	O
+that	O
+the	O
+complications	O
+had	O
+reduced	O
+to	O
+a	O
+very	O
+low	O
+rate	O
+(	O
+in	O
+2	O
+cases	O
+lead	O
+tip	O
+displacement	O
+and	O
+pouch	O
+haematoma	O
+occurred	O
+respectively	O
+)	O
+,	O
+the	O
+Authors	O
+consider	O
+the	O
+adopted	O
+method	O
+an	O
+useful	O
+approach	O
+for	O
+PMK	O
+implantation	O
+particularly	O
+when	O
+the	O
+use	O
+of	O
+the	O
+vena	O
+cephalica	O
+is	O
+deemed	O
+impossible	O
+.	O
+
+When	O
+two	O
+determinations	O
+were	O
+performed	O
+on	O
+12	O
+samples	O
+of	O
+plasma	O
+taken	O
+from	O
+normal	O
+adults	O
+in	O
+October	O
+,	O
+the	O
+values	O
+were	O
+22	O
+.	O
+6	O
++	O
+/	O
+-	O
+4	O
+.	O
+8	O
+and	O
+21	O
+.	O
+0	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+ng	O
+/	O
+ml	O
+,	O
+respectively	O
+.	O
+
+The	O
+six	O
+commonest	O
+causes	O
+of	O
+death	O
+varied	O
+in	O
+the	O
+three	O
+ethnic	O
+groups	O
+.	O
+
+Although	O
+Grice	O
+'	O
+s	O
+operation	O
+has	O
+been	O
+used	O
+all	O
+over	O
+the	O
+world	O
+,	O
+no	O
+systematic	O
+account	O
+of	O
+it	O
+has	O
+been	O
+found	O
+in	O
+the	O
+literature	O
+(	O
+including	O
+publications	O
+dealing	O
+with	O
+technique	O
+)	O
+,	O
+which	O
+presents	O
+it	O
+in	O
+terms	O
+related	O
+to	O
+the	O
+basic	O
+"	O
+classical	O
+"	O
+principles	O
+on	O
+which	O
+the	O
+operation	O
+was	O
+conceived	O
+.	O
+
+(	O
+5	O
+)	O
+No	O
+changes	O
+were	O
+observed	O
+in	O
+the	O
+gastric	O
+venous	O
+blood	O
+flow	O
+by	O
+continuous	O
+intravenous	O
+injection	O
+of	O
+cimetidine	O
+,	O
+but	O
+by	O
+rapid	O
+injection	O
+both	O
+the	O
+flow	O
+was	O
+augmented	O
+and	O
+the	O
+systemic	O
+blood	O
+pressure	O
+decreased	O
+transiently	O
+.	O
+
+Study	O
+on	O
+re	O
+-	O
+establishment	O
+of	O
+ovulation	O
+after	O
+termination	O
+of	O
+sex	O
+-	O
+steroidal	O
+treatment	O
+-	O
+-	O
+compared	O
+with	O
+re	O
+-	O
+appearance	O
+of	O
+ovulation	O
+after	O
+abortion	O
+and	O
+premature	O
+delivery	O
+.	O
+
+Pharmacokinetics	O
+of	O
+Carbamazepine	O
+in	O
+man	O
+:	O
+a	O
+review	O
+.	O
+
+Of	O
+the	O
+compounds	O
+tested	O
+,	O
+alpha	O
+-	O
+(	O
+3	O
+-	O
+methyl	O
+-	O
+2	O
+-	O
+quinoxalinyl	O
+)	O
+-	O
+N	O
+-	O
+methylnitrone	O
+1	O
+,	O
+4	O
+-	O
+dioxide	O
+(	O
+2	O
+)	O
+was	O
+the	O
+most	O
+active	O
+agent	O
+in	O
+vivo	O
+against	O
+the	O
+gram	O
+-	O
+negative	O
+and	O
+the	O
+gram	O
+-	O
+positive	O
+organisms	O
+.	O
+
+Changes	O
+in	O
+ionic	O
+content	O
+of	O
+the	O
+mucous	O
+suggest	O
+that	O
+cholinergic	O
+mechanisms	O
+affect	O
+pressure	O
+in	O
+the	O
+excretory	O
+duct	O
+of	O
+the	O
+gland	O
+.	O
+
+Calves	O
+fed	O
+MCT	O
+-	O
+milk	O
+had	O
+significantly	O
+lower	O
+blood	O
+cholesterol	O
+than	O
+calves	O
+fed	O
+T	O
+-	O
+or	O
+SBO	O
+-	O
+milk	O
+.	O
+
+Under	O
+halothane	O
+anesthesia	O
+,	O
+the	O
+flow	O
+pneumocardiogram	O
+(	O
+PnCG	O
+)	O
+and	O
+its	O
+time	O
+derivative	O
+(	O
+acceleration	O
+pneumocardiogram	O
+or	O
+dPn	O
+/	O
+dt	O
+)	O
+were	O
+transduced	O
+during	O
+apnea	O
+by	O
+a	O
+small	O
+high	O
+-	O
+gain	O
+pneumotachograph	O
+.	O
+
+Sensory	O
+kindling	O
+:	O
+implications	O
+for	O
+development	O
+of	O
+sensory	O
+prostheses	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+stereotypy	O
+can	O
+be	O
+evoked	O
+also	O
+in	O
+the	O
+case	O
+when	O
+the	O
+striatal	O
+dopaminergic	O
+tone	O
+is	O
+normal	O
+or	O
+even	O
+below	O
+normal	O
+:	O
+it	O
+is	O
+the	O
+equilibrium	O
+of	O
+the	O
+striatal	O
+cholinergic	O
+-	O
+dopaminergic	O
+systems	O
+which	O
+must	O
+be	O
+shifted	O
+towards	O
+dopamine	O
+,	O
+which	O
+is	O
+necessary	O
+for	O
+the	O
+development	O
+of	O
+this	O
+behavioral	O
+manifestation	O
+.	O
+
+In	O
+the	O
+duodenum	O
+a	O
+small	O
+part	O
+of	O
+the	O
+administered	O
+dose	O
+was	O
+transformed	O
+to	O
+3H	O
+-	O
+alpha	O
+-	O
+acetyldigoxin	O
+.	O
+
+Functional	O
+effects	O
+following	O
+subacute	O
+administration	O
+.	O
+
+Although	O
+it	O
+has	O
+been	O
+shown	O
+that	O
+it	O
+is	O
+possible	O
+to	O
+use	O
+orally	O
+administered	O
+testosterone	O
+to	O
+maintain	O
+se	O
+-	O
+T	O
+levels	O
+in	O
+the	O
+normal	O
+male	O
+range	O
+,	O
+the	O
+convenience	O
+to	O
+the	O
+patient	O
+must	O
+be	O
+balanced	O
+against	O
+the	O
+cost	O
+and	O
+possible	O
+side	O
+effects	O
+of	O
+the	O
+large	O
+doses	O
+required	O
+.	O
+
+Contrary	O
+to	O
+1	O
+,	O
+8	O
+-	O
+dihydroxy	O
+-	O
+9	O
+-	O
+anthrone	O
+,	O
+1	O
+,	O
+8	O
+,	O
+9	O
+-	O
+triacetoxyanthracene	O
+and	O
+1	O
+,	O
+8	O
+-	O
+diacetoxy	O
+-	O
+9	O
+-	O
+anthrone	O
+are	O
+effective	O
+against	O
+psoriatic	O
+lesions	O
+without	O
+accompanying	O
+inflammations	O
+of	O
+the	O
+skin	O
+.	O
+
+Etiopathogenetic	O
+and	O
+therapeutic	O
+problems	O
+in	O
+acute	O
+orbital	O
+inflammation	O
+
+Nursing	O
+of	O
+patients	O
+with	O
+gynecological	O
+diseases	O
+
+We	O
+measured	O
+basal	O
+plasma	O
+prolactin	B-GENE
+concentrations	O
+(	O
+in	O
+samples	O
+obtained	O
+during	O
+the	O
+early	O
+follicular	O
+phase	O
+)	O
+in	O
+25	O
+normal	O
+(	O
+control	O
+)	O
+women	O
+and	O
+in	O
+a	O
+similar	O
+group	O
+of	O
+40	O
+patients	O
+with	O
+a	O
+long	O
+-	O
+standing	O
+history	O
+of	O
+infertility	O
+.	O
+
+Ovarian	O
+allotransplantation	O
+in	O
+human	O
+.	O
+
+Screening	O
+of	O
+asthma	O
+patients	O
+by	O
+determination	O
+of	O
+IgE	B-GENE
+and	O
+by	O
+comprehension	O
+of	O
+spectrum	O
+of	O
+allergospecific	B-GENE
+IgE	I-GENE
+antibodies	I-GENE
+
+The	O
+induction	O
+of	O
+seizures	O
+in	O
+"	O
+Papio	O
+papio	O
+"	O
+following	O
+allylglycine	O
+alone	O
+or	O
+in	O
+combination	O
+with	O
+intermittent	O
+photic	O
+stimulation	O
+
+A	O
+highly	O
+significant	O
+correlation	O
+was	O
+found	O
+between	O
+the	O
+presence	O
+of	O
+fibrinolytic	O
+degradation	O
+products	O
+(	O
+FDP	O
+)	O
+and	O
+the	O
+incidence	O
+of	O
+nephropathy	O
+and	O
+renal	O
+insufficiency	O
+,	O
+as	O
+well	O
+as	O
+between	O
+the	O
+presence	O
+of	O
+fibrin	B-GENE
+monomers	I-GENE
+(	O
+Godal	O
+'	O
+s	O
+ethanol	O
+-	O
+gelification	O
+test	O
+)	O
+and	O
+the	O
+evolutive	O
+signs	O
+of	O
+the	O
+primary	O
+disease	O
+(	O
+fever	O
+,	O
+accelerated	O
+ESR	O
+)	O
+.	O
+
+In	O
+girls	O
+prolactin	B-GENE
+levels	O
+rise	O
+at	O
+stage	O
+2	O
+,	O
+and	O
+are	O
+higher	O
+after	O
+menarche	O
+;	O
+in	O
+boys	O
+there	O
+is	O
+no	O
+change	O
+in	O
+prolactin	B-GENE
+levels	O
+.	O
+
+2	O
+cases	O
+of	O
+toxic	O
+lymphomononucleosis	O
+
+Such	O
+an	O
+hemoglobin	B-GENE
+solution	O
+was	O
+shown	O
+to	O
+exhibit	O
+a	O
+high	O
+affinity	O
+for	O
+oxygen	O
+and	O
+a	O
+low	O
+Bohr	O
+effect	O
+(	O
+assessed	O
+from	O
+the	O
+delta	O
+log	O
+Po2	O
+/	O
+delta	O
+pH	O
+ratio	O
+)	O
+.	O
+
+A	O
+one	O
+-	O
+week	O
+ulcer	O
+therapy	O
+with	O
+atropine	O
+and	O
+Vikalin	O
+(	O
+Roter	O
+)	O
+led	O
+to	O
+a	O
+significant	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+reduction	O
+of	O
+the	O
+nocturnal	O
+proteolytic	O
+activity	O
+.	O
+
+In	O
+one	O
+patient	O
+with	O
+severe	O
+diarrhea	O
+the	O
+estriol	O
+concentration	O
+in	O
+serum	O
+was	O
+low	O
+until	O
+the	O
+intestinal	O
+function	O
+normalised	O
+and	O
+the	O
+estriol	O
+concentration	O
+went	O
+up	O
+exactly	O
+when	O
+the	O
+diarrhea	O
+stopped	O
+.	O
+
+Serum	O
+levels	O
+of	O
+IgG	B-GENE
+and	O
+IgM	B-GENE
+were	O
+also	O
+raised	O
+,	O
+but	O
+contrary	O
+to	O
+the	O
+findings	O
+of	O
+other	O
+observers	O
+IgA	B-GENE
+levels	O
+were	O
+normal	O
+.	O
+
+Experimental	O
+ischemic	O
+heart	O
+disease	O
+induced	O
+by	O
+thromboxane	O
+A2	O
+in	O
+rabbits	O
+.	O
+
+Vitrectomy	O
+in	O
+ocular	O
+traumatology	O
+
+To	O
+study	O
+the	O
+sensitivity	O
+of	O
+some	O
+central	O
+brain	O
+structures	O
+to	O
+the	O
+action	O
+of	O
+an	O
+electromagnetic	O
+field	O
+of	O
+decimeter	O
+waves	O
+(	O
+EMF	O
+of	O
+DW	O
+)	O
+a	O
+dynamic	O
+investigation	O
+of	O
+single	O
+unit	O
+activity	O
+was	O
+undertaken	O
+.	O
+
+No	O
+systematic	O
+L	O
+-	O
+R	O
+differences	O
+were	O
+observed	O
+.	O
+
+A	O
+decrease	O
+of	O
+the	O
+lysozyme	B-GENE
+activity	O
+coincided	O
+with	O
+the	O
+clinical	O
+improvement	O
+of	O
+the	O
+bacterial	O
+meningitis	O
+.	O
+
+1	O
+The	O
+effects	O
+in	O
+normal	O
+subjects	O
+of	O
+a	O
+single	O
+oral	O
+dose	O
+of	O
+Motival	O
+(	O
+one	O
+tablet	O
+,	O
+containing	O
+fluphenazine	O
+0	O
+.	O
+5	O
+mg	O
+and	O
+nortriptyline	O
+10	O
+mg	O
+)	O
+on	O
+the	O
+contingent	O
+negative	O
+variation	O
+(	O
+CNV	O
+)	O
+,	O
+reaction	O
+time	O
+,	O
+heart	O
+rate	O
+,	O
+blood	O
+pressure	O
+and	O
+self	O
+-	O
+rating	O
+scales	O
+for	O
+alertness	O
+,	O
+anxiety	O
+,	O
+tension	O
+,	O
+detachment	O
+and	O
+depression	O
+were	O
+compared	O
+with	O
+those	O
+of	O
+diazepam	O
+(	O
+5	O
+mg	O
+and	O
+7	O
+.	O
+5	O
+mg	O
+)	O
+and	O
+placebo	O
+or	O
+propranolol	O
+(	O
+60	O
+mg	O
+)	O
+.	O
+
+Stress	O
+effects	O
+on	O
+affiliation	O
+preferences	O
+among	O
+subjects	O
+possessing	O
+the	O
+type	O
+A	O
+coronary	O
+-	O
+prone	O
+behavior	O
+pattern	O
+.	O
+
+These	O
+show	O
+that	O
+the	O
+collagen	B-GENE
+in	O
+this	O
+tissue	O
+is	O
+modified	O
+compared	O
+with	O
+that	O
+in	O
+tendon	O
+.	O
+
+Smoking	O
+was	O
+regarded	O
+as	O
+the	O
+major	O
+contribution	O
+to	O
+pulmonary	O
+dysfunction	O
+.	O
+
+The	O
+malignity	O
+of	O
+nevoid	O
+lentigo	O
+.	O
+
+These	O
+responses	O
+were	O
+compared	O
+with	O
+others	O
+in	O
+the	O
+same	O
+subjects	O
+under	O
+the	O
+same	O
+conditions	O
+and	O
+it	O
+was	O
+concluded	O
+that	O
+the	O
+antihypertensive	O
+effect	O
+of	O
+labetalol	O
+is	O
+explained	O
+by	O
+concurrent	O
+blockade	O
+of	O
+alpha	B-GENE
+-	I-GENE
+and	I-GENE
+beta	I-GENE
+-	I-GENE
+adrenoceptors	I-GENE
+.	O
+
+Diuretics	O
+:	O
+basic	O
+clinical	O
+pharmacology	O
+and	O
+therapeutic	O
+use	O
+.	O
+
+Three	O
+patients	O
+with	O
+four	O
+renoureteral	O
+units	O
+have	O
+undergone	O
+single	O
+-	O
+stage	O
+reconstruction	O
+involving	O
+ureteroureterostomy	O
+and	O
+ipsilateral	O
+ureteroneocystostomy	O
+following	O
+temporary	O
+loop	O
+cutaneous	O
+ureterostomy	O
+.	O
+
+Internally	O
+oriented	O
+patients	O
+'	O
+scores	O
+on	O
+Rotter	O
+'	O
+s	O
+Internal	O
+-	O
+External	O
+Locus	O
+of	O
+Control	O
+Scale	O
+remained	O
+the	O
+same	O
+over	O
+treatment	O
+but	O
+those	O
+of	O
+externally	O
+oriented	O
+patients	O
+shifted	O
+toward	O
+greater	O
+internal	O
+control	O
+.	O
+
+Action	O
+of	O
+strontium	O
+-	O
+90	O
+and	O
+metaphos	O
+on	O
+Cyprinus	O
+carpio	O
+
+Kodak	O
+XV	O
+-	O
+2	O
+film	O
+is	O
+wrapped	O
+around	O
+a	O
+cylindrical	O
+water	O
+-	O
+filled	O
+phantom	O
+and	O
+the	O
+dose	O
+distribution	O
+is	O
+recorded	O
+.	O
+
+Diagnosis	O
+and	O
+differential	O
+diagnosis	O
+
+The	O
+multiple	O
+factors	O
+affecting	O
+plasma	O
+renin	B-GENE
+activity	O
+in	O
+essential	O
+hypertension	O
+.	O
+
+Cortisone	O
+induced	O
+bone	O
+changes	O
+and	O
+its	O
+response	O
+to	O
+lipid	O
+clearing	O
+agents	O
+.	O
+
+When	O
+blood	O
+samples	O
+of	O
+patients	O
+with	O
+hyperbilirubinemia	O
+were	O
+analyzed	O
+,	O
+direct	O
+measurement	O
+of	O
+ZPP	O
+by	O
+this	O
+fluorimeter	O
+yielded	O
+significantly	O
+higher	O
+levels	O
+than	O
+did	O
+an	O
+alternate	O
+extraction	O
+method	O
+.	O
+
+Delayed	O
+hypersensitivity	O
+in	O
+man	O
+:	O
+effects	O
+of	O
+systemic	O
+anticoagulation	O
+.	O
+
+Experimental	O
+studies	O
+on	O
+virus	O
+excretion	O
+and	O
+non	O
+-	O
+arthropod	O
+transmission	O
+.	O
+
+Prevention	O
+of	O
+acute	O
+paraquat	O
+toxicity	O
+in	O
+rats	O
+by	O
+superoxide	B-GENE
+dismutase	I-GENE
+.	O
+
+Increased	O
+urinary	O
+riboflavin	O
+excretion	O
+resulting	O
+from	O
+boric	O
+acid	O
+ingestion	O
+.	O
+
+Radionuclide	O
+angiography	O
+and	O
+static	O
+whole	O
+body	O
+imaging	O
+performed	O
+with	O
+technetium	O
+-	O
+99m	O
+-	O
+labeled	O
+particulates	O
+can	O
+clearly	O
+demonstrate	O
+differential	O
+shunting	O
+in	O
+patients	O
+with	O
+patent	O
+ductus	O
+arteriosus	O
+(	O
+PDA	O
+)	O
+with	O
+Eisenmenger	O
+physiology	O
+.	O
+
+Looming	O
+detectors	O
+in	O
+the	O
+human	O
+visual	O
+pathway	O
+.	O
+
+Escherichia	O
+of	O
+a	O
+single	O
+sero	O
+-	O
+anzymatic	O
+type	O
+(	O
+06a6b	O
+:	O
+K13	O
+:	O
+H1	O
+)	O
+were	O
+isolated	O
+in	O
+a	O
+group	O
+affection	O
+.	O
+
+The	O
+method	O
+described	O
+may	O
+prove	O
+useful	O
+in	O
+studying	O
+the	O
+physiology	O
+of	O
+the	O
+nasal	O
+cycle	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+we	O
+obtained	O
+easily	O
+understandable	O
+EEG	O
+-	O
+information	O
+which	O
+has	O
+never	O
+previously	O
+been	O
+available	O
+to	O
+us	O
+.	O
+
+Analysis	O
+of	O
+liver	O
+biopsy	O
+specimens	O
+from	O
+patients	O
+with	O
+hepatitis	O
+showed	O
+a	O
+large	O
+variation	O
+in	O
+the	O
+mean	O
+iron	O
+content	O
+of	O
+the	O
+liver	O
+ferritin	B-GENE
+molecules	O
+.	O
+
+Angiotensin	B-GENE
+effect	O
+in	O
+the	O
+human	O
+kidney	O
+.	O
+
+Procion	O
+yellow	O
+dye	O
+was	O
+injected	O
+intracellularly	O
+into	O
+large	O
+auditory	O
+fibers	O
+of	O
+goldfish	O
+to	O
+investigate	O
+the	O
+relationship	O
+between	O
+the	O
+response	O
+type	O
+of	O
+these	O
+fibers	O
+and	O
+their	O
+site	O
+of	O
+termination	O
+in	O
+the	O
+saccular	O
+macula	O
+.	O
+
+Incidental	O
+findings	O
+in	O
+the	O
+epidermis	O
+and	O
+in	O
+the	O
+intraepidermal	O
+eccrine	O
+sweat	O
+duct	O
+units	O
+.	O
+
+Silicosis	O
+mortality	O
+
+These	O
+consisted	O
+of	O
+beading	O
+and	O
+strictures	O
+mainly	O
+of	O
+the	O
+intrahepatic	O
+biliary	O
+tree	O
+(	O
+IHB	O
+)	O
+.	O
+
+Pentane	O
+and	O
+ethane	O
+,	O
+which	O
+arise	O
+during	O
+lipid	O
+peroxidation	O
+in	O
+vivo	O
+,	O
+were	O
+measured	O
+by	O
+gas	O
+chromatography	O
+in	O
+breath	O
+samples	O
+of	O
+rats	O
+fed	O
+for	O
+8	O
+weeks	O
+a	O
+vitamin	O
+E	O
+-	O
+deficient	O
+diet	O
+to	O
+which	O
+had	O
+been	O
+added	O
+0	O
+,	O
+11	O
+,	O
+or	O
+40	O
+IU	O
+vitamin	O
+E	O
+acetate	O
+per	O
+kg	O
+.	O
+
+The	O
+effect	O
+of	O
+pure	O
+natural	O
+porcine	B-GENE
+secretin	I-GENE
+on	O
+endocrine	O
+and	O
+exocrine	O
+pancreatic	O
+secretion	O
+was	O
+studied	O
+in	O
+the	O
+totally	O
+isolated	O
+perfused	O
+porcine	O
+pancreas	O
+.	O
+
+Biometric	O
+analysis	O
+of	O
+intraocular	O
+lens	O
+power	O
+required	O
+to	O
+produce	O
+emmetropia	O
+:	O
+results	O
+of	O
+450	O
+implants	O
+.	O
+
+Althoug	O
+RBF	O
+tended	O
+to	O
+increase	O
+after	O
+the	O
+therapy	O
+,	O
+there	O
+was	O
+no	O
+statistically	O
+significant	O
+change	O
+in	O
+RBF	O
+,	O
+GFR	O
+and	O
+cardiac	O
+output	O
+.	O
+
+Six	O
+patients	O
+with	O
+glomerulonephritis	O
+in	O
+association	O
+with	O
+a	O
+ventriculovascular	O
+shunt	O
+were	O
+treated	O
+with	O
+three	O
+basic	O
+modes	O
+of	O
+therapy	O
+.	O
+
+The	O
+mass	O
+of	O
+UO2	O
+in	O
+the	O
+extrapulmonary	O
+bronchi	O
+and	O
+first	O
+bifurcation	O
+decreased	O
+more	O
+slowly	O
+over	O
+0	O
+-	O
+-	O
+8	O
+d	O
+after	O
+inhalation	O
+than	O
+the	O
+corresponding	O
+mass	O
+on	O
+the	O
+trachea	O
+.	O
+
+Synovial	O
+cysts	O
+of	O
+the	O
+hip	O
+joint	O
+
+A	O
+sharp	O
+outbreak	O
+of	O
+influenza	O
+A	O
+occurred	O
+on	O
+the	O
+base	O
+during	O
+February	O
+that	O
+was	O
+due	O
+to	O
+an	O
+A	O
+/	O
+Texas	O
+/	O
+1	O
+/	O
+77	O
+-	O
+like	O
+virus	O
+,	O
+a	O
+variant	O
+of	O
+the	O
+A	O
+/	O
+Victoria	O
+/	O
+3	O
+/	O
+75	O
+prototpye	O
+.	O
+
+Because	O
+decreases	O
+in	O
+the	O
+disfluency	O
+rates	O
+of	O
+stutterers	O
+were	O
+observed	O
+during	O
+the	O
+presentation	O
+of	O
+all	O
+three	O
+stimulus	O
+words	O
+,	O
+the	O
+data	O
+failed	O
+to	O
+support	O
+the	O
+operant	O
+model	O
+.	O
+
+Effect	O
+of	O
+time	O
+and	O
+dose	O
+on	O
+alterations	O
+following	O
+inhalation	O
+of	O
+plutonium	O
+-	O
+239	O
+dioxide	O
+aerosol	O
+in	O
+rat	O
+.	O
+
+In	O
+biopsies	O
+CK	B-GENE
+-	I-GENE
+MB	I-GENE
+fraction	O
+of	O
+total	O
+myocardial	O
+CPK	B-GENE
+was	O
+37	O
+%	O
+,	O
+the	O
+total	B-GENE
+-	I-GENE
+CPK	I-GENE
+activity	O
+of	O
+human	O
+skeletal	O
+muscles	O
+still	O
+shows	O
+a	O
+5	O
+%	O
+fraction	O
+of	O
+CK	B-GENE
+-	I-GENE
+MB	I-GENE
+.	O
+
+Value	O
+of	O
+determination	O
+of	O
+alkaline	B-GENE
+phosphatase	I-GENE
+isoenzymes	I-GENE
+for	O
+differential	O
+diagnosis	O
+of	O
+obstructive	O
+jaundice	O
+and	O
+biliary	O
+liver	O
+cirrhosis	O
+
+Several	O
+free	O
+2nd	O
+-	O
+generation	O
+schizonts	O
+,	O
+which	O
+varied	O
+in	O
+diameter	O
+from	O
+11	O
+to	O
+21	O
+.	O
+6	O
+micrometer	O
+,	O
+were	O
+found	O
+on	O
+the	O
+epithelial	O
+surface	O
+of	O
+the	O
+cecum	O
+.	O
+
+The	O
+calculated	O
+pD2	O
+values	O
+were	O
+8	O
+.	O
+8	O
+for	O
+E	O
+,	O
+8	O
+.	O
+6	O
+for	O
+DHE	O
+and	O
+6	O
+.	O
+6	O
+for	O
+M	O
+.	O
+
+Newcastle	O
+disease	O
+virus	O
+surveillance	O
+in	O
+Hong	O
+Kong	O
+on	O
+local	O
+and	O
+imported	O
+poultry	O
+.	O
+
+It	O
+was	O
+postulated	O
+that	O
+persistent	O
+challenge	O
+by	O
+M	O
+.	O
+leprae	O
+or	O
+its	O
+antigens	O
+to	O
+the	O
+IgA	B-GENE
+immunocytes	O
+of	O
+the	O
+intestinal	O
+epithelium	O
+might	O
+have	O
+induced	O
+tolerance	O
+leading	O
+to	O
+IgA	B-GENE
+deficiency	O
+and	O
+subsequent	O
+subtotal	O
+atrophy	O
+of	O
+the	O
+intestinal	O
+villi	O
+in	O
+the	O
+patients	O
+with	O
+lepromatous	O
+leprosy	O
+.	O
+
+Treatment	O
+of	O
+hypertension	O
+with	O
+a	O
+combination	O
+of	O
+the	O
+adrenergic	B-GENE
+beta	I-GENE
+receptor	I-GENE
+blockader	O
+,	O
+obsidan	O
+,	O
+and	O
+the	O
+vasodilator	O
+,	O
+apressin	O
+
+Orthop	O
+.	O
+
+Thyroid	O
+disease	O
+and	O
+pregnancy	O
+.	O
+
+To	O
+minimize	O
+reflux	O
+into	O
+the	O
+blind	O
+loop	O
+,	O
+a	O
+number	O
+of	O
+technical	O
+steps	O
+are	O
+considered	O
+indispensable	O
+:	O
+1	O
+)	O
+fluted	O
+section	O
+of	O
+the	O
+jejunal	O
+stump	O
+;	O
+2	O
+)	O
+isoperistaltic	O
+construction	O
+of	O
+the	O
+anastomosis	O
+and	O
+,	O
+particularly	O
+,	O
+3	O
+)	O
+the	O
+creation	O
+of	O
+a	O
+single	O
+or	O
+double	O
+valve	O
+system	O
+upstream	O
+from	O
+the	O
+anastomosis	O
+by	O
+spiral	O
+introflexion	O
+of	O
+the	O
+mucosa	O
+using	O
+seroserous	O
+stitches	O
+parallel	O
+and	O
+perpendicular	O
+to	O
+the	O
+ileal	O
+lumen	O
+.	O
+
+At	O
+this	O
+stage	O
+,	O
+the	O
+eventual	O
+high	O
+mortality	O
+of	O
+acute	O
+ischemia	O
+is	O
+established	O
+whatever	O
+the	O
+urgency	O
+of	O
+the	O
+operation	O
+or	O
+the	O
+skill	O
+with	O
+which	O
+it	O
+is	O
+performed	O
+.	O
+
+Pathogens	O
+(	O
+Staphylococcus	O
+aureus	O
+or	O
+Gram	O
+-	O
+negative	O
+bacilli	O
+)	O
+were	O
+isolated	O
+from	O
+only	O
+one	O
+member	O
+of	O
+staff	O
+in	O
+small	O
+numbers	O
+and	O
+irregularly	O
+and	O
+rarely	O
+in	O
+large	O
+numbers	O
+from	O
+patients	O
+.	O
+
+Reaction	O
+times	O
+to	O
+tachistoscopically	O
+presented	O
+stimuli	O
+in	O
+diabetics	O
+
+Two	O
+out	O
+of	O
+five	O
+patients	O
+undergoing	O
+selective	O
+spinal	O
+arteriography	O
+developed	O
+transient	O
+neurological	O
+complications	O
+during	O
+the	O
+injection	O
+of	O
+Urografin	O
+310	O
+M	O
+.	O
+
+The	O
+data	O
+indicate	O
+a	O
+three	O
+-	O
+phase	O
+reaction	O
+after	O
+B1	O
+injection	O
+:	O
+Phase	O
+1	O
+-	O
+-	O
+shortly	O
+after	O
+injection	O
+there	O
+is	O
+a	O
+drop	O
+of	O
+all	O
+parameters	O
+lasting	O
+for	O
+30	O
+sec	O
+.	O
+
+Serum	B-GENE
+relaxin	I-GENE
+levels	O
+in	O
+prostaglandin	O
+E2	O
+induced	O
+abortions	O
+.	O
+
+A	O
+-	O
+-	O
+A	O
+natural	O
+hydrostatic	O
+phenomenon	O
+,	O
+at	O
+the	O
+level	O
+of	O
+the	O
+ends	O
+of	O
+the	O
+plantar	O
+arcs	O
+,	O
+diffuses	O
+body	O
+weight	O
+,	O
+as	O
+PAIN	O
+plays	O
+the	O
+role	O
+of	O
+outsentry	O
+(	O
+fig	O
+.	O
+-	O
+-	O
+1	O
+)	O
+(	O
+5	O
+)	O
+;	O
+B	O
+-	O
+-	O
+Plantar	O
+perforating	O
+ulceration	O
+(	O
+PPU	O
+)	O
+is	O
+caused	O
+by	O
+a	O
+combination	O
+of	O
+INSENSITIVITY	O
+and	O
+TRAUMATIS	O
+(	O
+1	O
+)	O
+;	O
+C	O
+-	O
+-	O
+The	O
+patient	O
+reposing	O
+,	O
+as	O
+body	O
+weight	O
+(	O
+traumatism	O
+)	O
+effects	O
+disappear	O
+,	O
+cicatrization	O
+process	O
+can	O
+be	O
+easily	O
+observed	O
+;	O
+D	O
+-	O
+-	O
+PNEUMATIC	O
+INSOLE	O
+,	O
+being	O
+elastic	O
+,	O
+diffuses	O
+localized	O
+compression	O
+at	O
+the	O
+ends	O
+of	O
+the	O
+plantar	O
+arcs	O
+,	O
+reduces	O
+attrition	O
+,	O
+makes	O
+easier	O
+blood	O
+circulation	O
+,	O
+as	O
+well	O
+as	O
+cure	O
+and	O
+prophylaxis	O
+of	O
+PPU	O
+(	O
+fig	O
+.	O
+-	O
+-	O
+6	O
+)	O
+(	O
+3	O
+)	O
+.	O
+
+Effect	O
+of	O
+indoramin	O
+in	O
+small	O
+doses	O
+on	O
+the	O
+central	O
+vasomotor	O
+loci	O
+has	O
+been	O
+studied	O
+in	O
+chloralose	O
+anesthetized	O
+cats	O
+by	O
+localizing	O
+it	O
+to	O
+the	O
+central	O
+sites	O
+.	O
+
+Contingency	O
+contracting	O
+between	O
+clients	O
+and	O
+their	O
+parents	O
+/	O
+caregivers	O
+was	O
+used	O
+to	O
+specify	O
+consequences	O
+for	O
+daily	O
+self	O
+-	O
+monitoring	O
+,	O
+reduced	O
+caloric	O
+intake	O
+,	O
+weight	O
+loss	O
+,	O
+and	O
+exercise	O
+.	O
+
+Dietetics	O
+of	O
+childhood	O
+-	O
+and	O
+juvenile	O
+diabetes	O
+
+The	O
+results	O
+of	O
+a	O
+quantitative	O
+study	O
+of	O
+vasculosyncytial	O
+membranes	O
+in	O
+123	O
+placentas	O
+are	O
+presented	O
+.	O
+
+The	O
+micromethod	O
+uses	O
+microcuvettes	O
+and	O
+substitutes	O
+ferrozine	O
+for	O
+the	O
+bathophenanthroline	O
+chromogen	O
+of	O
+the	O
+ICSH	O
+.	O
+
+Platelet	O
+serotonin	O
+(	O
+5	O
+-	O
+HT	O
+)	O
+and	O
+5	B-GENE
+-	I-GENE
+HT	I-GENE
+releasing	I-GENE
+factor	I-GENE
+in	O
+plasma	O
+of	O
+migrainous	O
+patients	O
+.	O
+
+The	O
+vigilance	O
+task	O
+and	O
+the	O
+measurement	O
+of	O
+attentional	O
+deficits	O
+.	O
+
+The	O
+December	O
+armed	O
+revolt	O
+in	O
+Moscow	O
+and	O
+the	O
+paramedical	O
+personnel	O
+
+The	O
+motor	O
+unit	O
+viewed	O
+from	O
+above	O
+.	O
+
+Avian	O
+reproductive	O
+system	O
+:	O
+daily	O
+variations	O
+in	O
+responses	O
+to	O
+hormones	O
+.	O
+
+Biological	O
+properties	O
+of	O
+sumithion	O
+.	O
+
+Serological	O
+studies	O
+of	O
+antibodies	O
+to	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+in	O
+infectious	O
+mononucleosis	O
+
+Carcinoembryonic	B-GENE
+antigen	I-GENE
+(	O
+CEA	B-GENE
+)	O
+procedures	O
+and	O
+clinical	O
+evaluation	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+a	O
+global	O
+assessment	O
+patients	O
+showed	O
+a	O
+highly	O
+significant	O
+preference	O
+for	O
+imipramine	O
+compared	O
+with	O
+placebo	O
+as	O
+adjunctive	O
+therapy	O
+.	O
+
+39	O
+-	O
+47	O
+.	O
+
+Absorption	O
+varied	O
+between	O
+65	O
+and	O
+95	O
+per	O
+cent	O
+,	O
+with	O
+a	O
+mean	O
+absorption	O
+of	O
+80	O
+per	O
+cent	O
+,	O
+in	O
+both	O
+pregnant	O
+and	O
+non	O
+-	O
+pregnant	O
+subjects	O
+.	O
+
+Advances	O
+in	O
+the	O
+management	O
+of	O
+gynecologic	O
+cancer	O
+-	O
+-	O
+radiation	O
+therapy	O
+.	O
+
+The	O
+clinico	O
+-	O
+pathological	O
+data	O
+from	O
+a	O
+patient	O
+with	O
+irreversible	O
+post	O
+-	O
+partum	O
+renal	O
+failure	O
+(	O
+IPRF	O
+)	O
+are	O
+presented	O
+.	O
+
+Dialyzable	O
+transfer	B-GENE
+factor	I-GENE
+.	O
+
+19	O
+-	O
+32	O
+.	O
+
+Rheumatoid	B-GENE
+factor	I-GENE
+and	O
+antinuclear	O
+antibody	O
+tests	O
+were	O
+frequently	O
+positive	O
+,	O
+and	O
+reactions	O
+to	O
+gold	O
+therapy	O
+were	O
+more	O
+frequent	O
+than	O
+in	O
+other	O
+rheumatoid	O
+populations	O
+.	O
+
+This	O
+report	O
+presents	O
+an	O
+analysis	O
+of	O
+the	O
+vocal	O
+repertoire	O
+of	O
+howler	O
+monkeys	O
+(	O
+Alouatta	O
+palliata	O
+)	O
+observed	O
+during	O
+a	O
+field	O
+study	O
+in	O
+southwestern	O
+Panama	O
+.	O
+
+Up	O
+to	O
+now	O
+the	O
+number	O
+of	O
+patients	O
+examined	O
+is	O
+about	O
+300	O
+,	O
+additionally	O
+6	O
+persons	O
+who	O
+underwent	O
+binephrectomy	O
+.	O
+
+Deflunia	O
+was	O
+well	O
+tolerated	O
+by	O
+25	O
+patients	O
+,	O
+very	O
+well	O
+tolerated	O
+by	O
+2	O
+.	O
+
+III	O
+.	O
+
+A	O
+new	O
+instrument	O
+has	O
+been	O
+designed	O
+for	O
+freeze	O
+-	O
+fracturing	O
+of	O
+biological	O
+material	O
+in	O
+ultra	O
+high	O
+vacuum	O
+.	O
+
+Pancreatic	O
+and	O
+biliary	O
+secretion	O
+and	O
+gastric	O
+emptying	O
+rates	O
+of	O
+a	O
+liquid	O
+test	O
+meal	O
+(	O
+LTM	O
+)	O
+were	O
+determined	O
+in	O
+normal	O
+persons	O
+,	O
+in	O
+patients	O
+with	O
+subtotal	O
+gastrectomy	O
+with	O
+gastroduodenostomy	O
+(	O
+STG	O
+-	O
+BI	O
+)	O
+or	O
+with	O
+gastrojejunostomy	O
+(	O
+STG	O
+-	O
+BII	O
+)	O
+,	O
+and	O
+in	O
+patients	O
+with	O
+truncal	O
+vagotomy	O
+and	O
+pyloroplasty	O
+(	O
+V	O
+&	O
+P	O
+)	O
+.	O
+
+Also	O
+,	O
+except	O
+in	O
+one	O
+patient	O
+who	O
+developed	O
+gallstones	O
+following	O
+institution	O
+of	O
+colestipol	O
+,	O
+saturation	O
+of	O
+gallbladder	O
+bile	O
+with	O
+cholesterol	O
+was	O
+not	O
+markedly	O
+increased	O
+by	O
+this	O
+drug	O
+alone	O
+.	O
+
+A	O
+diagnosis	O
+of	O
+MS	O
+was	O
+made	O
+based	O
+on	O
+subtle	O
+neurologic	O
+signs	O
+,	O
+spinal	O
+fluid	O
+gamma	B-GENE
+globulin	I-GENE
+elevations	O
+,	O
+and	O
+abnormalities	O
+in	O
+neuropsychological	O
+testing	O
+.	O
+
+If	O
+,	O
+however	O
+,	O
+the	O
+mean	O
+temperature	O
+rise	O
+was	O
+higher	O
+(	O
+0	O
+.	O
+57	O
+degrees	O
+C	O
+or	O
+0	O
+.	O
+69	O
+degrees	O
+C	O
+)	O
+,	O
+such	O
+a	O
+selection	O
+practically	O
+resulted	O
+in	O
+the	O
+disappearance	O
+of	O
+'	O
+passable	O
+'	O
+qualifications	O
+in	O
+the	O
+triplet	O
+groups	O
+and	O
+a	O
+great	O
+predominance	O
+of	O
+'	O
+to	O
+be	O
+rejected	O
+'	O
+qualifications	O
+in	O
+the	O
+large	O
+groups	O
+.	O
+
+The	O
+elevated	O
+Viso	O
+V	O
+in	O
+the	O
+RDS	O
+group	O
+suggests	O
+an	O
+increase	O
+in	O
+small	O
+airway	O
+resistance	O
+secondary	O
+to	O
+the	O
+disease	O
+or	O
+to	O
+its	O
+therapy	O
+.	O
+
+The	O
+psychological	O
+tests	O
+consisted	O
+of	O
+a	O
+free	O
+-	O
+recall	O
+task	O
+,	O
+a	O
+test	O
+for	O
+visuomotor	O
+coordination	O
+and	O
+a	O
+recognition	O
+task	O
+.	O
+
+Selective	O
+bronchial	O
+intubation	O
+in	O
+the	O
+management	O
+of	O
+unilateral	O
+pulmonary	O
+interstitial	O
+emphysema	O
+.	O
+
+The	O
+background	O
+processes	O
+depending	O
+on	O
+the	O
+etiological	O
+factor	O
+and	O
+the	O
+character	O
+of	O
+lesion	O
+of	O
+the	O
+epithelium	O
+are	O
+divided	O
+into	O
+dyshormonal	O
+,	O
+inflammatory	O
+,	O
+and	O
+posttraumatic	O
+.	O
+
+The	O
+sense	O
+of	O
+self	O
+.	O
+
+Eleven	O
+strains	O
+of	O
+Fusarium	O
+poae	O
+and	O
+F	O
+.	O
+sporotrichioides	O
+from	O
+the	O
+U	O
+.	O
+S	O
+.	O
+S	O
+.	O
+R	O
+.	O
+and	O
+7	O
+strains	O
+of	O
+these	O
+species	O
+and	O
+one	O
+of	O
+F	O
+.	O
+sporotrichioides	O
+var	O
+.	O
+tricinctum	O
+from	O
+U	O
+.	O
+S	O
+.	O
+A	O
+.	O
+and	O
+France	O
+have	O
+been	O
+compared	O
+as	O
+to	O
+their	O
+capacity	O
+to	O
+yield	O
+T	B-GENE
+-	I-GENE
+2	I-GENE
+toxin	I-GENE
+.	O
+
+Current	O
+diagnostic	O
+uses	O
+of	O
+computerized	O
+tomography	O
+in	O
+clinical	O
+medicine	O
+.	O
+
+A	O
+follow	O
+-	O
+up	O
+study	O
+of	O
+22	O
+patients	O
+with	O
+Ebstein	O
+'	O
+s	O
+anomaly	O
+has	O
+been	O
+performed	O
+.	O
+
+Deaths	O
+stopped	O
+11	O
+hours	O
+after	O
+copper	O
+concentrations	O
+decreased	O
+below	O
+0	O
+.	O
+2	O
+ppm	O
+and	O
+signs	O
+of	O
+distress	O
+stopped	O
+in	O
+surviving	O
+pinfish	O
+by	O
+approximately	O
+6	O
+hours	O
+after	O
+the	O
+last	O
+death	O
+.	O
+
+Recurrence	O
+of	O
+bladder	O
+tumors	O
+among	O
+the	O
+original	O
+9	O
+cases	O
+has	O
+occurred	O
+only	O
+among	O
+the	O
+5	O
+whose	O
+properdin	B-GENE
+levels	O
+remained	O
+below	O
+the	O
+median	O
+.	O
+
+Adaptation	O
+of	O
+taurocholate	O
+transport	O
+maximum	O
+to	O
+increased	O
+secretory	O
+load	O
+in	O
+the	O
+rat	O
+.	O
+
+Dangers	O
+in	O
+use	O
+of	O
+live	O
+-	O
+virus	O
+vaccines	O
+.	O
+
+Treatment	O
+with	O
+heparin	O
+,	O
+plasminogen	B-GENE
+activators	O
+and	O
+fibrinogenolytic	O
+agents	O
+was	O
+disappointing	O
+although	O
+renal	O
+function	O
+has	O
+stabilized	O
+in	O
+one	O
+patient	O
+on	O
+long	O
+term	O
+oral	O
+anticoagulant	O
+therapy	O
+.	O
+
+In	O
+diethyl	O
+ether	O
+solution	O
+the	O
+main	O
+peak	O
+is	O
+that	O
+of	O
+2	O
+-	O
+benzylidenamio	O
+-	O
+1	O
+-	O
+phenylpropane	O
+,	O
+which	O
+has	O
+a	O
+retention	O
+time	O
+of	O
+23	O
+,	O
+2	O
+minutes	O
+under	O
+the	O
+condition	O
+delineated	O
+.	O
+
+Amikacin	O
+was	O
+used	O
+in	O
+the	O
+treatment	O
+of	O
+56	O
+serious	O
+gram	O
+-	O
+negative	O
+infections	O
+in	O
+54	O
+patients	O
+of	O
+whom	O
+47	O
+survived	O
+.	O
+
+The	O
+data	O
+normally	O
+available	O
+are	O
+insufficient	O
+and	O
+take	O
+no	O
+account	O
+of	O
+the	O
+direction	O
+of	O
+recirculation	O
+,	O
+which	O
+may	O
+be	O
+a	O
+determining	O
+factor	O
+.	O
+
+The	O
+acids	O
+were	O
+obtained	O
+by	O
+hydrolysis	O
+of	O
+the	O
+corresponding	O
+esters	O
+,	O
+and	O
+their	O
+anti	O
+-	O
+inflammatory	O
+activity	O
+was	O
+tested	O
+.	O
+
+Unrecognized	O
+amnionitis	O
+and	O
+prematurity	O
+:	O
+a	O
+preliminary	O
+report	O
+.	O
+
+Evaluation	O
+of	O
+the	O
+new	O
+Gravigard	O
+IUCD	O
+inserter	O
+.	O
+
+Bacterial	O
+meningitis	O
+secondary	O
+to	O
+abscess	O
+of	O
+the	O
+nasal	O
+septum	O
+.	O
+
+Serum	B-GENE
+amylase	I-GENE
+became	O
+markedly	O
+elevated	O
+(	O
+2	O
+,	O
+624	O
+CU	O
+/	O
+100	O
+ml	O
+)	O
+,	O
+as	O
+did	O
+the	O
+serum	O
+FFA	O
+(	O
+29	O
+.	O
+19	O
+mEq	O
+/	O
+liter	O
+)	O
+.	O
+
+In	O
+the	O
+control	O
+preparation	O
+before	O
+weight	O
+was	O
+allowed	O
+to	O
+increase	O
+,	O
+isogravimetric	O
+capillary	O
+pressure	O
+(	O
+Pci	O
+)	O
+averaged	O
+8	O
+mmHg	O
+lower	O
+than	O
+colloid	O
+osmotic	O
+pressure	O
+of	O
+the	O
+plasma	O
+(	O
+IIp	O
+)	O
+.	O
+
+The	O
+morphological	O
+effects	O
+of	O
+two	O
+snake	O
+venoms	O
+,	O
+N	O
+.	O
+naja	O
+and	O
+A	O
+.	O
+piscivorus	O
+,	O
+and	O
+of	O
+the	O
+Direct	B-GENE
+Lytic	I-GENE
+Factor	I-GENE
+and	O
+Phospholipase	B-GENE
+-	I-GENE
+A	I-GENE
+,	O
+compounds	O
+purified	O
+from	O
+N	O
+.	O
+naja	O
+crude	O
+venom	O
+,	O
+were	O
+investigated	O
+on	O
+lung	O
+and	O
+cremaster	O
+vessels	O
+of	O
+rats	O
+.	O
+
+Since	O
+GAGs	O
+are	O
+the	O
+components	O
+of	O
+cartilage	O
+matrix	O
+,	O
+the	O
+depletion	O
+of	O
+which	O
+is	O
+associated	O
+with	O
+osteoarthrosis	O
+,	O
+a	O
+method	O
+for	O
+measuring	O
+sulphated	O
+GAG	O
+synthesis	O
+in	O
+culture	O
+has	O
+been	O
+investigated	O
+.	O
+
+The	O
+length	O
+scales	O
+of	O
+the	O
+turbulence	O
+were	O
+also	O
+estimated	O
+:	O
+at	O
+a	O
+Reynolds	O
+number	O
+near	O
+4	O
+,	O
+000	O
+the	O
+macroscale	O
+is	O
+about	O
+1	O
+.	O
+25	O
+mm	O
+,	O
+the	O
+Taylor	O
+microscale	O
+is	O
+about	O
+0	O
+.	O
+85	O
+mm	O
+,	O
+and	O
+the	O
+Kolmogoroff	O
+scale	O
+is	O
+near	O
+0	O
+.	O
+075	O
+mm	O
+.	O
+
+Well	O
+-	O
+visualised	O
+arteriograms	O
+of	O
+the	O
+limbs	O
+can	O
+be	O
+obtained	O
+by	O
+xeroradiography	O
+after	O
+rapid	O
+manual	O
+injection	O
+of	O
+contrast	O
+-	O
+medium	O
+into	O
+an	O
+arm	O
+vein	O
+,	O
+as	O
+demonstrated	O
+in	O
+28	O
+patients	O
+.	O
+
+No	O
+hypotension	O
+was	O
+noted	O
+in	O
+patients	O
+with	O
+toxemia	O
+and	O
+only	O
+2	O
+ran	O
+a	O
+fever	O
+above	O
+37	O
+.	O
+5	O
+degrees	O
+C	O
+.	O
+
+The	O
+sera	O
+and	O
+nasal	O
+secretions	O
+of	O
+142	O
+patients	O
+,	O
+who	O
+were	O
+positive	O
+in	O
+HD	O
+or	O
+mites	O
+skin	O
+test	O
+,	O
+were	O
+subjected	O
+to	O
+a	O
+radioallergosorbent	O
+test	O
+(	O
+RAST	O
+)	O
+for	O
+estimating	O
+the	O
+specific	O
+IgE	B-GENE
+antibody	I-GENE
+activity	O
+to	O
+mites	O
+.	O
+
+Diallylnitrosamine	O
+(	O
+DAN	O
+)	O
+,	O
+one	O
+of	O
+the	O
+few	O
+nitrosamines	O
+tested	O
+thus	O
+far	O
+that	O
+has	O
+not	O
+induced	O
+neoplasms	O
+in	O
+rats	O
+,	O
+caused	O
+a	O
+high	O
+incidence	O
+of	O
+respiratory	O
+tract	O
+tumors	O
+in	O
+Syrian	O
+golden	O
+hamsters	O
+treated	O
+sc	O
+with	O
+single	O
+or	O
+weekly	O
+doses	O
+of	O
+the	O
+compound	O
+.	O
+
+Haemodynamic	O
+responses	O
+to	O
+antagonism	O
+of	O
+bocurarine	O
+block	O
+with	O
+atropine	O
+-	O
+neostigmine	O
+mixture	O
+in	O
+children	O
+.	O
+
+The	O
+mechanism	O
+by	O
+which	O
+large	O
+molecules	O
+,	O
+such	O
+as	O
+the	O
+diphosphonate	O
+99mTc	O
+-	O
+labeled	O
+EHDP	O
+or	O
+99mTc	O
+-	O
+labeled	O
+pyrophosphate	O
+,	O
+pass	O
+through	O
+capillaries	O
+in	O
+bone	O
+is	O
+by	O
+passive	O
+diffusion	O
+.	O
+
+Twenty	O
+-	O
+nine	O
+days	O
+after	O
+injection	O
+of	O
+5	O
+.	O
+8	O
+mCi	O
+of	O
+Tc	O
+-	O
+99m	O
+,	O
+which	O
+gives	O
+28	O
+rads	O
+to	O
+the	O
+testis	O
+,	O
+the	O
+number	O
+of	O
+sperm	O
+hads	O
+decreased	O
+to	O
+70	O
+%	O
+of	O
+control	O
+.	O
+
+Self	O
+-	O
+emasculation	O
+is	O
+the	O
+end	O
+result	O
+of	O
+an	O
+unusual	O
+psychiatric	O
+disorder	O
+,	O
+which	O
+initially	O
+requires	O
+surgical	O
+treatment	O
+.	O
+
+Possibility	O
+of	O
+a	O
+TSH	B-GENE
+-	O
+Screening	O
+method	O
+for	O
+detection	O
+of	O
+hypothyroidism	O
+in	O
+the	O
+newborn	O
+
+Thus	O
+analysis	O
+indicated	O
+no	O
+reliable	O
+evidence	O
+that	O
+conscious	O
+presleep	O
+suggestions	O
+become	O
+incorporated	O
+into	O
+dream	O
+content	O
+.	O
+
+The	O
+prevalence	O
+of	O
+hepatitis	B-GENE
+B	I-GENE
+surface	I-GENE
+antigen	I-GENE
+(	O
+HBsAg	B-GENE
+)	O
+and	O
+anti	B-GENE
+-	I-GENE
+HBs	I-GENE
+was	O
+determined	O
+by	O
+a	O
+sensitive	O
+double	O
+-	O
+antibody	O
+radio	O
+-	O
+immunoassay	O
+technique	O
+in	O
+a	O
+series	O
+of	O
+patients	O
+with	O
+chronic	O
+liver	O
+diseases	O
+.	O
+
+Decreased	O
+cardiac	O
+glycogen	O
+following	O
+phenformin	O
+injection	O
+in	O
+hyperglycemic	O
+,	O
+hyperinsulinemic	O
+anaesthetized	O
+rats	O
+.	O
+
+Biological	O
+evaluation	O
+of	O
+mibolerone	O
+in	O
+the	O
+female	O
+Beagle	O
+.	O
+
+Levels	O
+of	O
+both	O
+PGF	O
+and	O
+PGFM	O
+were	O
+significantly	O
+higher	O
+during	O
+early	O
+spontaneous	O
+labour	O
+,	O
+at	O
+a	O
+cervical	O
+dilatation	O
+of	O
+less	O
+than	O
+4	O
+cm	O
+,	O
+than	O
+before	O
+the	O
+onset	O
+of	O
+labour	O
+.	O
+
+Propranolol	O
+(	O
+Inderal	O
+)	O
+administered	O
+in	O
+a	O
+dose	O
+which	O
+blocks	O
+the	O
+beta	O
+-	O
+adrenergic	O
+apparatus	O
+of	O
+the	O
+heart	O
+prevents	O
+the	O
+development	O
+of	O
+the	O
+positive	O
+inotropic	O
+effect	O
+of	O
+therapeutic	O
+doses	O
+of	O
+strophanthin	O
+K	O
+on	O
+a	O
+hypodynamic	O
+left	O
+ventricular	O
+myocardium	O
+.	O
+
+Recent	O
+studies	O
+have	O
+shown	O
+the	O
+rat	O
+larynx	O
+to	O
+be	O
+an	O
+important	O
+organ	O
+in	O
+the	O
+evaluation	O
+of	O
+irritancy	O
+of	O
+inhaled	O
+materials	O
+.	O
+
+Scanning	O
+electron	O
+microscopic	O
+investigations	O
+on	O
+the	O
+formation	O
+of	O
+Reissner	O
+'	O
+s	O
+fiber	O
+in	O
+Rattus	O
+rattus	O
+
+Feeding	O
+behavior	O
+,	O
+circannual	O
+body	O
+weight	O
+and	O
+hibernation	O
+rhythms	O
+in	O
+European	O
+hamsters	O
+lesioned	O
+in	O
+the	O
+noradrenergic	O
+ascending	O
+bundles	O
+
+Role	O
+of	O
+the	O
+infectious	O
+-	O
+disease	O
+specialist	O
+of	O
+a	O
+polyclinic	O
+in	O
+reducing	O
+the	O
+incidence	O
+of	O
+communicable	O
+diseases	O
+
+These	O
+observed	O
+drug	O
+interactions	O
+,	O
+plus	O
+the	O
+known	O
+effect	O
+of	O
+probenecid	O
+to	O
+block	O
+secretion	O
+of	O
+PZA	O
+,	O
+have	O
+to	O
+be	O
+considered	O
+in	O
+evaluating	O
+the	O
+effect	O
+of	O
+the	O
+two	O
+drugs	O
+given	O
+together	O
+,	O
+compared	O
+to	O
+the	O
+effect	O
+of	O
+each	O
+drug	O
+given	O
+separately	O
+.	O
+
+At	O
+a	O
+systolic	O
+blood	O
+pressure	O
+(	O
+BP	O
+)	O
+of	O
+60	O
+mmHg	O
+,	O
+C02	O
+responsiveness	O
+was	O
+abolished	O
+,	O
+but	O
+was	O
+maintained	O
+at	O
+higher	O
+levels	O
+of	O
+BP	O
+.	O
+
+On	O
+cessation	O
+of	O
+steroid	O
+therapy	O
+the	O
+patient	O
+was	O
+noted	O
+to	O
+have	O
+radiologic	O
+manifestations	O
+of	O
+hypertrophic	O
+osteoarthropathy	O
+(	O
+HOA	O
+)	O
+as	O
+well	O
+as	O
+clinical	O
+and	O
+laboratory	O
+features	O
+of	O
+rheumatoid	O
+arthritis	O
+(	O
+RA	O
+)	O
+.	O
+
+The	O
+effect	O
+of	O
+food	O
+on	O
+procainamide	O
+absorption	O
+.	O
+
+After	O
+giving	O
+a	O
+survey	O
+on	O
+the	O
+situation	O
+of	O
+antibiotic	O
+resistance	O
+in	O
+the	O
+region	O
+of	O
+Northern	O
+Bavaria	O
+during	O
+1973	O
+/	O
+74	O
+and	O
+comparing	O
+the	O
+activity	O
+of	O
+a	O
+sulfamethoxazole	O
+(	O
+SMZ	O
+)	O
+trimethoprim	O
+(	O
+TMP	O
+)	O
+combination	O
+to	O
+other	O
+commonly	O
+used	O
+antibiotics	O
+and	O
+chemotherapeutic	O
+agents	O
+,	O
+the	O
+results	O
+of	O
+tests	O
+with	O
+the	O
+new	O
+combination	O
+of	O
+N1	O
+-	O
+(	O
+4	O
+,	O
+5	O
+-	O
+dimethyl	O
+-	O
+2	O
+-	O
+oxazolyl	O
+)	O
+-	O
+sulfanilamide	O
+)	O
+(	O
+sulfamoxole	O
+)	O
+and	O
+2	O
+,	O
+4	O
+-	O
+diamino	O
+-	O
+5	O
+-	O
+(	O
+3	O
+,	O
+4	O
+,	O
+5	O
+-	O
+trimethoxy	O
+-	O
+benzyl	O
+)	O
+-	O
+pyrimidine	O
+(	O
+trimethoprim	O
+)	O
+at	O
+a	O
+ratio	O
+of	O
+5	O
+:	O
+1	O
+(	O
+CN	O
+3123	O
+;	O
+Nevin	O
+,	O
+Supristol	O
+)	O
+are	O
+compared	O
+to	O
+those	O
+of	O
+tests	O
+with	O
+TMP	O
+/	O
+SMZ	O
+.	O
+
+RESULTS	O
+:	O
+Total	O
+IgE	B-GENE
+levels	O
+showed	O
+a	O
+tendency	O
+to	O
+diminish	O
+.	O
+
+Does	O
+afferent	O
+loop	O
+syndrome	O
+exist	O
+?	O
+]	O
+It	O
+is	O
+the	O
+author	O
+'	O
+s	O
+opinion	O
+that	O
+diagnosis	O
+of	O
+the	O
+"	O
+adducent	O
+loop	O
+syndrome	O
+"	O
+is	O
+unlikely	O
+to	O
+be	O
+correct	O
+in	O
+patients	O
+subjected	O
+to	O
+Billroth	O
+-	O
+II	O
+gastrectomy	O
+.	O
+
+Letter	O
+:	O
+Is	O
+actinic	O
+(	O
+solar	O
+)	O
+damage	O
+the	O
+provoking	O
+cause	O
+of	O
+'	O
+post	O
+-	O
+inflammatory	O
+elastolysis	O
+and	O
+cutis	O
+laxa	O
+(	O
+PECL	O
+)	O
+'	O
+?	O
+
+These	O
+data	O
+suggest	O
+that	O
+spontaneous	O
+recovery	O
+of	O
+central	O
+respiratory	O
+function	O
+after	O
+intoxication	O
+with	O
+Soman	O
+or	O
+Sarin	O
+may	O
+not	O
+be	O
+related	O
+to	O
+the	O
+return	O
+of	O
+AChE	B-GENE
+activity	O
+.	O
+
+Batch	O
+cultures	O
+of	O
+S	O
+.	O
+mutans	O
+serotype	O
+a	O
+demonstrated	O
+no	O
+growth	O
+on	O
+MSB	O
+agar	O
+.	O
+
+Crisis	O
+of	O
+the	O
+therapeutic	O
+community	O
+in	O
+Great	O
+Britain	O
+
+Pregnant	O
+women	O
+at	O
+term	O
+had	O
+the	O
+lowest	O
+levels	O
+of	O
+antithrombin	B-GENE
+III	I-GENE
+.	O
+
+Hematology	O
+problem	O
+of	O
+the	O
+month	O
+:	O
+band	O
+or	O
+seg	O
+?	O
+
+It	O
+is	O
+possible	O
+that	O
+cyclic	O
+variations	O
+in	O
+heme	O
+turnover	O
+are	O
+related	O
+to	O
+changes	O
+in	O
+erythrocyte	O
+characteristics	O
+during	O
+the	O
+progesterone	O
+phase	O
+.	O
+
+Haemodilution	O
+in	O
+cardiopulmonary	O
+bypass	O
+using	O
+a	O
+gelatine	O
+derivative	O
+for	O
+priming	O
+.	O
+
+I	O
+.	O
+
+The	O
+performance	O
+of	O
+three	O
+commonly	O
+used	O
+chemical	O
+cartridge	O
+respirators	O
+for	O
+SO2	O
+was	O
+measured	O
+under	O
+working	O
+conditions	O
+in	O
+a	O
+copper	O
+smelter	O
+.	O
+
+The	O
+neuroleptic	O
+-	O
+induced	O
+increase	O
+in	O
+central	O
+DA	O
+turnover	O
+(	O
+an	O
+indicator	O
+for	O
+the	O
+degree	O
+of	O
+DA	B-GENE
+receptor	I-GENE
+blocking	O
+)	O
+was	O
+found	O
+to	O
+be	O
+positively	O
+correlated	O
+with	O
+the	O
+therapeutic	O
+effect	O
+of	O
+neuroleptics	O
+and	O
+the	O
+development	O
+of	O
+hypokinetic	O
+-	O
+rigid	O
+symptoms	O
+.	O
+
+Rainbow	O
+trout	O
+were	O
+obtained	O
+from	O
+a	O
+commercial	O
+trout	O
+farm	O
+,	O
+kept	O
+in	O
+running	O
+water	O
+and	O
+feeding	O
+in	O
+experimental	O
+pellets	O
+for	O
+4	O
+to	O
+8	O
+weeks	O
+.	O
+
+Stimulation	O
+of	O
+macrophage	O
+function	O
+by	O
+killed	O
+Bordetella	O
+pertussis	O
+cells	O
+did	O
+not	O
+show	O
+any	O
+beneficial	O
+effect	O
+as	O
+an	O
+increased	O
+susceptibility	O
+became	O
+apparent	O
+.	O
+
+Primary	O
+amenorrhoea	O
+in	O
+a	O
+phenotypically	O
+female	O
+individual	O
+with	O
+a	O
+karyotype	O
+46	O
+,	O
+xy	O
+and	O
+bilateral	O
+gonadoblastoma	O
+
+Toward	O
+absolute	O
+methods	O
+in	O
+clinical	O
+chemistry	O
+:	O
+application	O
+of	O
+mass	O
+fragmentography	O
+to	O
+high	O
+-	O
+accuracy	O
+analyses	O
+.	O
+
+Application	O
+of	O
+the	O
+2	O
+-	O
+deoxy	O
+-	O
+D	O
+-	O
+glucose	O
+method	O
+to	O
+the	O
+coupling	O
+of	O
+cerebral	O
+metabolism	O
+and	O
+blood	O
+flow	O
+.	O
+
+Serum	O
+gastrin	B-GENE
+levels	O
+did	O
+not	O
+change	O
+in	O
+either	O
+group	O
+;	O
+however	O
+,	O
+background	O
+serum	O
+gastrin	B-GENE
+concentrations	O
+were	O
+significantly	O
+greater	O
+for	O
+V	O
+&	O
+P	O
+patients	O
+than	O
+V	O
+&	O
+A	O
+patients	O
+throughout	O
+the	O
+study	O
+.	O
+
+Efferent	O
+projections	O
+of	O
+the	O
+ventral	O
+portion	O
+of	O
+the	O
+putamen	O
+to	O
+the	O
+frontal	O
+,	O
+parietal	O
+and	O
+temporal	O
+regions	O
+of	O
+the	O
+cat	O
+cerebral	O
+cortex	O
+
+Preflight	O
+,	O
+inflight	O
+,	O
+and	O
+postflight	O
+exercise	O
+response	O
+tests	O
+were	O
+conducted	O
+on	O
+the	O
+astronauts	O
+of	O
+the	O
+second	O
+Skylab	O
+mission	O
+(	O
+Skylab	O
+3	O
+)	O
+as	O
+part	O
+of	O
+an	O
+evaluation	O
+of	O
+physiological	O
+adaptation	O
+to	O
+long	O
+-	O
+term	O
+weightlessness	O
+.	O
+
+Mean	O
+corpuscular	B-GENE
+hemoglobin	I-GENE
+concentrations	O
+remained	O
+normal	O
+for	O
+48	O
+h	O
+and	O
+then	O
+decreased	O
+in	O
+both	O
+groups	O
+,	O
+the	O
+CO2	O
+group	O
+showing	O
+the	O
+larger	O
+decrease	O
+.	O
+
+All	O
+Cu	O
+values	O
+obtained	O
+from	O
+the	O
+organs	O
+investigated	O
+had	O
+reached	O
+a	O
+saturation	O
+level	O
+at	O
+8	O
+mug	O
+Cu	O
+/	O
+g	O
+diet	O
+with	O
+the	O
+exception	O
+of	O
+the	O
+values	O
+for	O
+body	O
+Cu	O
+found	O
+in	O
+the	O
+dams	O
+that	O
+were	O
+killed	O
+on	O
+the	O
+day	O
+of	O
+delivery	O
+.	O
+
+The	O
+effect	O
+of	O
+calcitonin	B-GENE
+,	O
+a	O
+large	O
+amount	O
+of	O
+calcium	O
+given	O
+orally	O
+,	O
+pentagastrin	O
+and	O
+glucagon	B-GENE
+on	O
+plasma	O
+47Ca	O
+radioactivity	O
+curves	O
+in	O
+subjects	O
+pretreated	O
+with	O
+47Ca	O
+was	O
+examined	O
+.	O
+
+State	O
+of	O
+the	O
+body	O
+in	O
+disorders	O
+of	O
+diurnal	O
+physiological	O
+rhythms	O
+and	O
+long	O
+-	O
+term	O
+hypokinesia	O
+
+The	O
+response	O
+of	O
+the	O
+plasma	B-GENE
+fibrinogen	I-GENE
+level	O
+to	O
+the	O
+subucutaneous	O
+injection	O
+of	O
+turpentine	O
+and	O
+to	O
+the	O
+intravenous	O
+injection	O
+of	O
+endotoxin	O
+was	O
+measured	O
+in	O
+normal	O
+rabbits	O
+and	O
+in	O
+rabbits	O
+made	O
+granulocytopenic	O
+and	O
+thrombocytopenic	O
+with	O
+busulfan	O
+.	O
+
+Constantly	O
+rectilinear	O
+pressure	O
+curves	O
+without	O
+uterine	O
+activities	O
+are	O
+interpreted	O
+as	O
+characteristic	O
+tocographic	O
+criteria	O
+of	O
+an	O
+advanced	O
+ectopic	O
+gravidity	O
+.	O
+
+Since	O
+myoglobin	B-GENE
+is	O
+co	O
+-	O
+extracted	O
+with	O
+the	O
+hemoglobin	B-GENE
+,	O
+the	O
+2	O
+heme	O
+pigments	O
+are	O
+separated	O
+in	O
+one	O
+portion	O
+of	O
+the	O
+extract	O
+by	O
+precipitating	O
+the	O
+hemoglobin	B-GENE
+in	O
+an	O
+85	O
+%	O
+(	O
+NH4	O
+)	O
+2SO4	O
+solution	O
+.	O
+
+Considering	O
+these	O
+sources	O
+of	O
+error	O
+some	O
+of	O
+the	O
+variability	O
+in	O
+the	O
+present	O
+investigation	O
+might	O
+be	O
+avoided	O
+by	O
+systematic	O
+instructions	O
+.	O
+
+E	O
+50	O
+,	O
+843	O
+(	O
+1994	O
+)	O
+]	O
+.	O
+
+Six	O
+patients	O
+with	O
+the	O
+diagnosis	O
+of	O
+acute	O
+mania	O
+were	O
+treated	O
+with	O
+high	O
+doses	O
+of	O
+the	O
+beta	O
+-	O
+adrenergic	O
+blocking	O
+agent	O
+propranolol	O
+.	O
+
+Effect	O
+of	O
+trauma	O
+on	O
+plasma	B-GENE
+glucagon	I-GENE
+and	O
+insulin	B-GENE
+concentrations	O
+in	O
+sheep	O
+.	O
+
+With	O
+the	O
+help	O
+of	O
+a	O
+nomogram	O
+one	O
+can	O
+read	O
+off	O
+the	O
+refraction	O
+,	O
+when	O
+axis	O
+length	O
+and	O
+corneal	O
+curvature	O
+are	O
+known	O
+.	O
+
+This	O
+up	O
+-	O
+grading	O
+of	O
+the	O
+final	O
+score	O
+by	O
+the	O
+CA	O
+component	O
+is	O
+greater	O
+(	O
+3	O
+-	O
+8	O
+%	O
+)	O
+in	O
+the	O
+less	O
+able	O
+students	O
+with	O
+scores	O
+below	O
+the	O
+mean	O
+level	O
+.	O
+
+Compared	O
+to	O
+controls	O
+,	O
+both	O
+UB	O
+and	O
+OCS	O
+rats	O
+showed	O
+a	O
+small	O
+but	O
+significant	O
+post	O
+-	O
+operative	O
+reduction	O
+in	O
+the	O
+nocturnality	O
+of	O
+drinking	O
+.	O
+
+Effect	O
+of	O
+indomethacin	O
+on	O
+coronary	O
+circulation	O
+:	O
+effect	O
+on	O
+ECG	O
+tracing	O
+
+Dual	O
+innervation	O
+of	O
+fast	O
+fibers	O
+in	O
+trunk	O
+muscles	O
+of	O
+lamprey	O
+larvae	O
+
+The	O
+feed	O
+consumed	O
+which	O
+was	O
+lowered	O
+by	O
+25	O
+%	O
+initially	O
+,	O
+did	O
+not	O
+alter	O
+later	O
+.	O
+
+Certain	O
+characteristics	O
+of	O
+eye	O
+changes	O
+in	O
+patients	O
+with	O
+pheochromocytoma	O
+including	O
+Sipple	O
+'	O
+s	O
+syndrome	O
+
+The	O
+color	O
+-	O
+word	O
+interference	O
+effect	O
+previously	O
+reported	O
+with	O
+normal	O
+populations	O
+when	O
+given	O
+the	O
+Stroop	O
+test	O
+was	O
+demonstrated	O
+for	O
+this	O
+retarded	O
+sample	O
+using	O
+a	O
+special	O
+format	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+under	O
+the	O
+selected	O
+conditions	O
+a	O
+linear	O
+dependence	O
+exists	O
+between	O
+the	O
+betaI	O
+%	O
+value	O
+and	O
+lgC	O
+within	O
+the	O
+range	O
+of	O
+0	O
+.	O
+5	O
+-	O
+-	O
+10	O
+mug	O
+ruscogenin	O
+.	O
+
+The	O
+influence	O
+of	O
+adrenergic	O
+nerves	O
+of	O
+the	O
+response	O
+of	O
+blood	O
+vessels	O
+in	O
+the	O
+rabbit	O
+ear	O
+to	O
+2	B-GENE
+-	I-GENE
+-	I-GENE
+phenylalanine	I-GENE
+-	I-GENE
+8	I-GENE
+-	I-GENE
+lysine	I-GENE
+vasopressin	I-GENE
+(	O
+Octapressin	B-GENE
+)	O
+.	O
+
+Potscoital	O
+test	O
+
+When	O
+a	O
+tumour	O
+is	O
+present	O
+nipple	O
+discharge	O
+is	O
+of	O
+little	O
+importance	O
+for	O
+the	O
+diagnosis	O
+and	O
+treatment	O
+.	O
+
+Studies	O
+of	O
+biochemical	O
+and	O
+morphological	O
+changes	O
+(	O
+between	O
+normal	O
+and	O
+treated	O
+animals	O
+)	O
+show	O
+that	O
+chrysotile	O
+induces	O
+an	O
+increase	O
+in	O
+the	O
+lung	O
+free	O
+cell	O
+population	O
+and	O
+pulmonary	O
+surfactant	O
+levels	O
+.	O
+
+Infrared	O
+measurements	O
+of	O
+temperature	O
+changes	O
+and	O
+estimates	O
+of	O
+the	O
+heating	O
+produced	O
+at	O
+the	O
+mical	O
+.	O
+
+Who	O
+says	O
+'	O
+National	O
+Health	O
+Dis	O
+-	O
+service	O
+'	O
+.	O
+
+Is	O
+criticism	O
+of	O
+patient	O
+care	O
+justified	O
+and	O
+does	O
+it	O
+have	O
+educational	O
+value	O
+?	O
+Patients	O
+'	O
+criticism	O
+contributes	O
+to	O
+improved	O
+patient	O
+care	O
+
+Critique	O
+of	O
+"	O
+Interactive	O
+Effects	O
+of	O
+Test	O
+Anxiety	O
+and	O
+Credit	O
+/	O
+No	O
+Credit	O
+or	O
+A	O
+-	O
+F	O
+Grade	O
+Condition	O
+upon	O
+Short	O
+-	O
+term	O
+and	O
+Long	O
+-	O
+term	O
+Recall	O
+of	O
+Course	O
+Information	O
+.	O
+
+These	O
+studies	O
+have	O
+shown	O
+that	O
+the	O
+majority	O
+of	O
+tested	O
+staphylococci	O
+were	O
+resistant	O
+to	O
+penicillin	O
+G	O
+,	O
+erythromycin	O
+,	O
+and	O
+produced	O
+beta	B-GENE
+-	I-GENE
+lactamase	I-GENE
+.	O
+
+Improvement	O
+of	O
+nursing	O
+instruction	O
+to	O
+be	O
+given	O
+at	O
+the	O
+time	O
+of	O
+discharge	O
+from	O
+the	O
+ward	O
+for	O
+premature	O
+infants	O
+
+No	O
+difference	O
+in	O
+the	O
+clinical	O
+acceptability	O
+could	O
+be	O
+ascertained	O
+between	O
+the	O
+two	O
+groups	O
+.	O
+
+After	O
+90	O
+d	O
+a	O
+subsurface	O
+,	O
+radiolucent	O
+caries	O
+-	O
+like	O
+lesion	O
+was	O
+observed	O
+in	O
+two	O
+specimens	O
+only	O
+.	O
+
+Plethysmographic	O
+technique	O
+and	O
+indirect	O
+blood	O
+pressure	O
+recordings	O
+were	O
+used	O
+.	O
+
+The	O
+second	O
+and	O
+third	O
+responded	O
+similarly	O
+to	O
+either	O
+a	O
+combined	O
+cyclophosphamide	O
++	O
+antilymphocyte	B-GENE
+globulin	I-GENE
+(	O
+ALG	B-GENE
+)	O
+treatment	O
+or	O
+to	O
+ALG	B-GENE
+administration	O
+preceded	O
+by	O
+a	O
+small	O
+dosage	O
+of	O
+cyclophosphamide	O
+,	O
+which	O
+had	O
+proved	O
+ineffective	O
+when	O
+administered	O
+alone	O
+.	O
+
+Evidence	O
+is	O
+presented	O
+that	O
+Leber	O
+'	O
+s	O
+military	O
+aneurysm	O
+retinitis	O
+is	O
+not	O
+a	O
+separate	O
+entity	O
+but	O
+a	O
+special	O
+form	O
+of	O
+Coats	O
+'	O
+disease	O
+.	O
+
+Fibrin	B-GENE
+cloaking	O
+along	O
+the	O
+catheter	O
+was	O
+found	O
+in	O
+20	O
+patients	O
+studied	O
+by	O
+pull	O
+-	O
+out	O
+arteriography	O
+and	O
+was	O
+unassociated	O
+with	O
+clinical	O
+symptoms	O
+.	O
+
+The	O
+influence	O
+of	O
+a	O
+mobile	O
+pupil	O
+on	O
+the	O
+response	O
+in	O
+the	O
+DC	O
+-	O
+ERG	O
+is	O
+demonstrated	O
+.	O
+
+A	O
+newly	O
+synthesized	O
+anti	O
+-	O
+inflammatory	O
+agent	O
+,	O
+Y	O
+-	O
+8004	O
+demonstrated	O
+a	O
+greater	O
+inhibition	O
+than	O
+did	O
+indomethacin	O
+(	O
+IM	O
+)	O
+.	O
+on	O
+inflammatory	O
+response	O
+such	O
+as	O
+ultraviolet	O
+erythema	O
+in	O
+guinea	O
+pigs	O
+,	O
+carrageenin	O
+edema	O
+,	O
+evans	O
+blue	O
+and	O
+carrageenin	O
+-	O
+induced	O
+pleuritis	O
+and	O
+acetic	O
+acid	O
+-	O
+induced	O
+peritonitis	O
+in	O
+rats	O
+.	O
+
+As	O
+stands	O
+shifted	O
+in	O
+dominance	O
+from	O
+pine	O
+to	O
+fir	O
+with	O
+age	O
+,	O
+subalpine	O
+fir	O
+appeared	O
+to	O
+maintain	O
+gradually	O
+increasing	O
+rates	O
+of	O
+whole	O
+-	O
+forest	O
+productivity	O
+until	O
+stands	O
+were	O
+approximately	O
+400	O
+years	O
+old	O
+.	O
+
+Alpha	B-GENE
+-	I-GENE
+1	I-GENE
+antitrypsin	I-GENE
+and	O
+Indian	O
+childhood	O
+cirrhosis	O
+.	O
+
+Lymphocyte	O
+subpopulations	O
+,	O
+serum	B-GENE
+IgE	I-GENE
+and	O
+total	O
+eosinophil	O
+counts	O
+in	O
+patients	O
+with	O
+bronchial	O
+asthma	O
+.	O
+
+A	O
+range	O
+of	O
+normal	O
+ventricular	O
+measurements	O
+for	O
+the	O
+EMI	O
+scan	O
+is	O
+suggested	O
+.	O
+
+A	O
+comparison	O
+of	O
+physical	O
+and	O
+cytogenetic	O
+estimates	O
+of	O
+radiation	O
+dose	O
+in	O
+patients	O
+treated	O
+with	O
+iodine	O
+-	O
+131	O
+for	O
+thyroid	O
+carcinoma	O
+.	O
+
+Technique	O
+for	O
+obtaining	O
+refined	O
+ceramics	O
+with	O
+dense	O
+mass	O
+
+Mean	O
+total	O
+lung	O
+capacity	O
+,	O
+functional	O
+residual	O
+capacity	O
+,	O
+and	O
+residual	O
+volume	O
+increased	O
+significantly	O
+,	O
+and	O
+the	O
+mean	O
+closing	O
+volume	O
+,	O
+the	O
+lung	O
+volume	O
+above	O
+residual	O
+volume	O
+at	O
+which	O
+phase	O
+IV	O
+begins	O
+,	O
+decreased	O
+significantly	O
+with	O
+11	O
+cm	O
+H20	O
+continuous	O
+positive	O
+airway	O
+pressure	O
+;	O
+differences	O
+at	O
+5	O
+cm	O
+H20	O
+were	O
+not	O
+significant	O
+.	O
+
+Current	O
+status	O
+of	O
+zinc	O
+deficiency	O
+in	O
+the	O
+pathogenesis	O
+of	O
+neurological	O
+,	O
+dermatological	O
+and	O
+musculoskeletal	O
+disorders	O
+.	O
+
+Calcium	O
+and	O
+phosphorus	O
+metabolism	O
+in	O
+chronic	O
+uremia	O
+.	O
+
+Modern	O
+studies	O
+,	O
+conducted	O
+with	O
+Delta	O
+-	O
+9	O
+-	O
+THC	O
+,	O
+in	O
+healthy	O
+voluntaries	O
+,	O
+again	O
+suggest	O
+the	O
+comparison	O
+or	O
+even	O
+the	O
+identity	O
+of	O
+the	O
+modifications	O
+caused	O
+by	O
+cannabis	O
+with	O
+sleep	O
+and	O
+dream	O
+.	O
+
+The	O
+correcting	O
+action	O
+of	O
+tropatepine	O
+hydrochloride	O
+upon	O
+the	O
+extrapyramidal	O
+effects	O
+induced	O
+by	O
+neuroleptics	O
+has	O
+been	O
+studied	O
+in	O
+32	O
+acute	O
+psychotic	O
+states	O
+.	O
+
+Epididymal	O
+growth	O
+was	O
+retarded	O
+in	O
+animals	O
+maintained	O
+solely	O
+on	O
+chickpea	O
+haulm	O
+and	O
+improved	O
+with	O
+supplementation	O
+.	O
+
+Two	O
+patients	O
+were	O
+treated	O
+with	O
+both	O
+regimens	O
+.	O
+
+Results	O
+obtained	O
+for	O
+chloramphenicol	O
+-	O
+containing	O
+preparations	O
+are	O
+presented	O
+,	O
+and	O
+both	O
+dissolution	O
+curves	O
+and	O
+cup	O
+-	O
+plate	O
+assays	O
+demonstrate	O
+that	O
+chloramphenicol	O
+has	O
+far	O
+superior	O
+release	O
+(	O
+and	O
+hence	O
+activity	O
+)	O
+from	O
+creams	O
+than	O
+from	O
+ophthalmic	O
+ointments	O
+.	O
+
+IgG	B-GENE
+levels	O
+of	O
+1	O
+/	O
+100	O
+were	O
+present	O
+in	O
+only	O
+four	O
+out	O
+of	O
+ten	O
+samples	O
+obtained	O
+150	O
+days	O
+after	O
+the	O
+clinical	O
+onset	O
+.	O
+
+Letter	O
+:	O
+Perspectives	O
+in	O
+bone	O
+marrow	O
+transplantation	O
+.	O
+
+Assessment	O
+of	O
+the	O
+carcinogenicity	O
+of	O
+non	O
+-	O
+nutritive	O
+sweetners	O
+II	O
+:	O
+Cyclamates	O
+and	O
+cyclohexylamine	O
+.	O
+
+The	O
+discordant	O
+behaviour	O
+in	O
+weakly	O
+infected	O
+mice	O
+was	O
+due	O
+to	O
+the	O
+occurrence	O
+in	O
+some	O
+animals	O
+of	O
+a	O
+second	O
+phase	O
+of	O
+more	O
+rapid	O
+increase	O
+of	O
+the	O
+parasitemia	O
+.	O
+
+Residual	O
+amphotericin	O
+B	O
+was	O
+detected	O
+in	O
+the	O
+feces	O
+of	O
+the	O
+mice	O
+only	O
+while	O
+they	O
+were	O
+receiving	O
+the	O
+0	O
+.	O
+3	O
+mg	O
+/	O
+ml	O
+dose	O
+level	O
+.	O
+
+There	O
+was	O
+a	O
+slight	O
+increase	O
+in	O
+total	O
+transferrin	B-GENE
+2	O
+hr	O
+after	O
+1	O
+tablet	O
+and	O
+values	O
+remained	O
+high	O
+throughout	O
+the	O
+experiment	O
+.	O
+
+Following	O
+intravenous	O
+administration	O
+,	O
+the	O
+myocardial	O
+concentration	O
+of	O
+tracer	O
+thallium	O
+-	O
+201	O
+,	O
+potassium	O
+-	O
+43	O
+,	O
+and	O
+rubidium	O
+-	O
+81	O
+were	O
+determined	O
+in	O
+mice	O
+;	O
+thallium	O
+was	O
+present	O
+in	O
+the	O
+greatest	O
+concentration	O
+in	O
+the	O
+myocardium	O
+(	O
+2	O
+.	O
+08	O
+%	O
+compared	O
+1	O
+.	O
+25	O
+%	O
+for	O
+potassium	O
+and	O
+1	O
+.	O
+15	O
+%	O
+for	O
+rubidium	O
+at	O
+10	O
+minutes	O
+)	O
+.	O
+
+Thromboplastin	B-GENE
+time	O
+,	O
+partial	O
+thromboplastin	B-GENE
+time	O
+,	O
+thrombin	B-GENE
+time	O
+,	O
+heat	O
+-	O
+dependent	O
+fibrin	B-GENE
+,	O
+clot	O
+retraction	O
+,	O
+and	O
+clotting	B-GENE
+factors	I-GENE
+II	I-GENE
+,	I-GENE
+V	I-GENE
+,	I-GENE
+VIII	I-GENE
+,	I-GENE
+IX	I-GENE
+,	I-GENE
+X	I-GENE
+,	O
+and	O
+the	O
+platelet	O
+count	O
+were	O
+determined	O
+.	O
+
+The	O
+data	O
+support	O
+the	O
+notion	O
+that	O
+suppression	O
+of	O
+images	O
+during	O
+binocular	O
+rivalry	O
+is	O
+independent	O
+in	O
+both	O
+eyes	O
+.	O
+
+Glycogen	O
+utilization	O
+was	O
+increased	O
+,	O
+but	O
+tissue	O
+levels	O
+of	O
+creatine	O
+phosphate	O
+,	O
+ATP	O
+,	O
+and	O
+lactate	O
+were	O
+similar	O
+to	O
+those	O
+in	O
+hearts	O
+receiving	O
+normal	O
+flow	O
+.	O
+
+The	O
+records	O
+from	O
+1948	O
+through	O
+1967	O
+of	O
+344	O
+previously	O
+untreated	O
+patients	O
+with	O
+squamous	O
+cell	O
+carcinoma	O
+of	O
+the	O
+oral	O
+cavity	O
+,	O
+oropharynx	O
+,	O
+supraglottic	O
+larynx	O
+and	O
+hypopharynx	O
+who	O
+had	O
+clinically	O
+positive	O
+cervical	O
+lymph	O
+node	O
+metastases	O
+staged	O
+N1	O
+,	O
+N2A	O
+,	O
+or	O
+N2B	O
+,	O
+and	O
+whose	O
+initial	O
+neck	O
+treatment	O
+consisted	O
+of	O
+external	O
+radiation	O
+therapy	O
+alone	O
+were	O
+reviewed	O
+.	O
+
+With	O
+0	O
+.	O
+5	O
+vol	O
+.	O
+-	O
+%	O
+,	O
+the	O
+corresponding	O
+values	O
+were	O
+345	O
+mumol	O
+/	O
+1	O
+(	O
+5	O
+.	O
+72	O
+mg	O
+/	O
+100	O
+ml	O
+)	O
+and	O
+137	O
+mumol	O
+/	O
+1	O
+(	O
+2	O
+.	O
+25	O
+mg	O
+/	O
+100	O
+ml	O
+)	O
+respectively	O
+.	O
+
+The	O
+authors	O
+describe	O
+the	O
+technique	O
+of	O
+transverse	O
+axial	O
+tomography	O
+of	O
+the	O
+spine	O
+and	O
+give	O
+a	O
+detailed	O
+description	O
+of	O
+the	O
+axial	O
+anatomy	O
+of	O
+the	O
+normal	O
+lumbar	O
+spine	O
+from	O
+L	O
+-	O
+4	O
+to	O
+the	O
+sacrum	O
+.	O
+
+Owing	O
+to	O
+parental	O
+attitude	O
+,	O
+a	O
+low	O
+protein	O
+diet	O
+(	O
+1	O
+-	O
+5	O
+g	O
+/	O
+kg	O
+)	O
+was	O
+introduced	O
+only	O
+late	O
+.	O
+
+In	O
+none	O
+of	O
+the	O
+44	O
+type	O
+I	O
+attacks	O
+and	O
+29	O
+type	O
+II	O
+attacks	O
+which	O
+were	O
+recorded	O
+did	O
+circulatory	O
+changes	O
+;	O
+the	O
+latter	O
+were	O
+different	O
+in	O
+the	O
+two	O
+groups	O
+.	O
+
+A	O
+clinically	O
+useful	O
+diagnostic	O
+method	O
+has	O
+been	O
+developed	O
+for	O
+detecting	O
+and	O
+quantitating	O
+periods	O
+of	O
+apnea	O
+in	O
+pediatric	O
+patients	O
+.	O
+
+The	O
+other	O
+hypoglycaemic	O
+patient	O
+showed	O
+an	O
+exaggerated	O
+insulin	B-GENE
+release	O
+in	O
+response	O
+to	O
+tolbutamide	O
+.	O
+
+Effect	O
+of	O
+ingestion	O
+of	O
+Norbiogest	O
+during	O
+the	O
+quiescent	O
+period	O
+of	O
+the	O
+genital	O
+organs	O
+
+Bulbar	O
+pouches	O
+were	O
+perfused	O
+with	O
+solutions	O
+of	O
+0	O
+.	O
+9	O
+%	O
+Na	O
+C1	O
+,	O
+0	O
+.	O
+1	O
+N	O
+HC1	O
+,	O
+40	O
+%	O
+glucose	O
+,	O
+40	O
+%	O
+NaC1	O
+,	O
+and	O
+40	O
+%	O
+peptone	O
+or	O
+with	O
+0	O
+.	O
+1	O
+%	O
+solutions	O
+of	O
+acetylcholine	O
+chloride	O
+.	O
+
+Liver	O
+microsomes	O
+of	O
+the	O
+shag	O
+showed	O
+smaller	O
+than	O
+8	O
+%	O
+of	O
+the	O
+epoxide	B-GENE
+hydrase	I-GENE
+activity	O
+and	O
+smaller	O
+than	O
+14	O
+%	O
+of	O
+the	O
+hydroxylating	O
+capacity	O
+of	O
+liver	O
+microsomes	O
+from	O
+the	O
+rat	O
+.	O
+
+A	O
+clinical	O
+,	O
+serological	O
+and	O
+prognostic	O
+study	O
+
+The	O
+American	O
+Burkitt	O
+Lymphoma	O
+Registry	O
+:	O
+a	O
+progress	O
+report	O
+.	O
+
+Vitrectomy	O
+with	O
+an	O
+alternative	O
+instrument	O
+system	O
+.	O
+
+The	O
+metabolic	O
+clearance	O
+rate	O
+of	O
+progesterone	O
+was	O
+295	O
++	O
+/	O
+-	O
+49	O
+(	O
+S	O
+.	O
+E	O
+.	O
+)	O
+1	O
+/	O
+day	O
+.	O
+
+The	O
+mean	O
+plasma	O
+sodium	O
+concentration	O
+which	O
+was	O
+135	O
+.	O
+95	O
+(	O
++	O
+/	O
+-	O
+SD	O
+4	O
+.	O
+14	O
+)	O
+mEq	O
+/	O
+kg	O
+before	O
+diuretic	O
+treatment	O
+was	O
+significantly	O
+decreased	O
+during	O
+treatment	O
+to	O
+129	O
+.	O
+19	O
+(	O
++	O
+/	O
+-	O
+SD	O
+2	O
+.	O
+77	O
+)	O
+mEq	O
+/	O
+kg	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+.	O
+
+Editorial	O
+:	O
+Low	O
+-	O
+dose	O
+heparin	O
+and	O
+the	O
+prevention	O
+of	O
+venous	O
+thromboembolic	O
+disease	O
+.	O
+
+Effects	O
+of	O
+perceptual	O
+salience	O
+on	O
+the	O
+matrix	O
+task	O
+performance	O
+of	O
+four	O
+-	O
+and	O
+six	O
+-	O
+year	O
+-	O
+old	O
+children	O
+.	O
+
+Glucose	B-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+phosphate	I-GENE
+dehydrogenase	I-GENE
+(	O
+G	B-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+PD	I-GENE
+)	O
+deficiency	O
+in	O
+the	O
+newborn	O
+.	O
+
+The	O
+eluting	O
+solvent	O
+was	O
+methanol	O
+-	O
+chloroform	O
+(	O
+10	O
++	O
+90	O
+)	O
+at	O
+a	O
+flow	O
+rate	O
+of	O
+2	O
+.	O
+0	O
+ml	O
+/	O
+min	O
+.	O
+
+The	O
+bronchial	O
+epithelia	O
+of	O
+all	O
+smoke	O
+-	O
+exposed	O
+animals	O
+were	O
+hyperplastic	O
+,	O
+and	O
+their	O
+ultrastructure	O
+showed	O
+invaginations	O
+,	O
+tilt	O
+of	O
+nuclear	O
+axes	O
+,	O
+an	O
+increase	O
+in	O
+the	O
+number	O
+and	O
+size	O
+of	O
+lysosomes	O
+and	O
+multivesiculated	O
+bodies	O
+,	O
+and	O
+increased	O
+numbers	O
+of	O
+enlarged	O
+intramitochondrial	O
+granules	O
+.	O
+
+The	O
+routine	O
+administration	O
+of	O
+fat	O
+-	O
+soluble	O
+vitamins	O
+appears	O
+unnecessary	O
+but	O
+it	O
+is	O
+prudent	O
+to	O
+measure	O
+prothrombin	B-GENE
+time	O
+and	O
+serum	O
+vitamins	O
+A	O
+and	O
+E	O
+at	O
+intervals	O
+.	O
+
+Prostaglandins	O
+F	O
+(	O
+PGF	O
+)	O
+were	O
+measured	O
+in	O
+uterine	O
+vein	O
+,	O
+ovarian	O
+artery	O
+,	O
+and	O
+jugular	O
+vein	O
+plasma	O
+and	O
+in	O
+the	O
+endometrial	O
+tissues	O
+at	O
+various	O
+times	O
+during	O
+the	O
+bovine	O
+estrous	O
+cycle	O
+,	O
+and	O
+were	O
+compared	O
+to	O
+peripheral	O
+plasma	O
+progesterone	O
+levels	O
+.	O
+
+Before	O
+this	O
+date	O
+,	O
+the	O
+drug	O
+directly	O
+inhibits	O
+fetal	O
+weight	O
+gain	O
+,	O
+whereas	O
+the	O
+sensitivity	O
+of	O
+the	O
+placenta	O
+is	O
+only	O
+transient	O
+at	O
+day	O
+16	O
+resulting	O
+in	O
+maximum	O
+weight	O
+decrease	O
+of	O
+this	O
+organ	O
+24	O
+h	O
+later	O
+.	O
+
+Groups	O
+of	O
+ten	O
+dependent	O
+and	O
+ten	O
+saline	O
+mice	O
+were	O
+singly	O
+tested	O
+in	O
+both	O
+light	O
+and	O
+dark	O
+conditions	O
+in	O
+each	O
+of	O
+five	O
+covered	O
+cylinders	O
+(	O
+2	O
+-	O
+23	O
+in	O
+high	O
+)	O
+.	O
+
+The	O
+effects	O
+initiated	O
+from	O
+the	O
+nucleus	O
+accumbens	O
+septi	O
+were	O
+most	O
+marked	O
+.	O
+
+The	O
+appearance	O
+of	O
+dyskinetic	O
+movement	O
+disorders	O
+in	O
+humans	O
+following	O
+the	O
+chronic	O
+use	O
+of	O
+levodopa	O
+or	O
+amphetamine	O
+may	O
+be	O
+a	O
+manifestation	O
+of	O
+similarly	O
+increased	O
+dopamine	B-GENE
+receptor	I-GENE
+site	I-GENE
+sensitivity	O
+within	O
+the	O
+striatum	O
+.	O
+
+Association	O
+with	O
+HL	B-GENE
+-	I-GENE
+A	I-GENE
+W	I-GENE
+-	I-GENE
+27	I-GENE
+.	O
+
+Letter	O
+:	O
+Lactose	O
+tolerance	O
+tests	O
+as	O
+a	O
+predictor	O
+of	O
+milk	O
+tolerance	O
+.	O
+
+Retinoblastoma	O
+:	O
+a	O
+study	O
+of	O
+natural	O
+history	O
+and	O
+prognosis	O
+of	O
+268	O
+cases	O
+.	O
+
+Like	O
+pineal	O
+melatonin	O
+,	O
+serum	O
+melatonin	O
+was	O
+high	O
+at	O
+mid	O
+-	O
+dark	O
+and	O
+low	O
+at	O
+mid	O
+-	O
+light	O
+.	O
+
+D	O
+.	O
+
+Atherosclerosis	O
+
+The	O
+authors	O
+concluded	O
+that	O
+ultrasonic	O
+Doppler	O
+-	O
+cardiography	O
+can	O
+be	O
+used	O
+for	O
+measuring	O
+the	O
+relative	O
+changes	O
+in	O
+the	O
+stroke	O
+volume	O
+.	O
+
+The	O
+attainment	O
+of	O
+sexual	O
+maturity	O
+in	O
+terms	O
+of	O
+secondary	O
+sexual	O
+characteristics	O
+,	O
+the	O
+production	O
+of	O
+spermatozoa	O
+in	O
+the	O
+male	O
+,	O
+and	O
+the	O
+cyclical	O
+female	O
+pattern	O
+with	O
+release	O
+of	O
+ova	O
+are	O
+end	O
+-	O
+points	O
+of	O
+the	O
+developmental	O
+process	O
+.	O
+
+Caution	O
+should	O
+be	O
+exercised	O
+in	O
+the	O
+use	O
+of	O
+these	O
+dyes	O
+for	O
+lymphograms	O
+.	O
+
+This	O
+reveals	O
+a	O
+new	O
+test	O
+for	O
+short	O
+saphenous	O
+incompetence	O
+and	O
+shows	O
+that	O
+14	O
+per	O
+cent	O
+of	O
+varices	O
+stem	O
+from	O
+a	O
+saphenopopliteal	O
+reflux	O
+.	O
+
+Three	O
+groups	O
+of	O
+patients	O
+who	O
+had	O
+undergone	O
+subtotal	O
+thyroidectomy	O
+for	O
+Graves	O
+'	O
+s	O
+disease	O
+,	O
+toxic	O
+multinodular	O
+goitre	O
+,	O
+or	O
+euthyroid	O
+multinodular	O
+goitre	O
+12	O
+to	O
+15	O
+years	O
+before	O
+and	O
+in	O
+whom	O
+a	O
+normal	O
+serum	O
+thyroxine	O
+(	O
+T	O
+-	O
+4	O
+)	O
+level	O
+was	O
+found	O
+were	O
+each	O
+divided	O
+into	O
+two	O
+subgroups	O
+on	O
+the	O
+basis	O
+of	O
+a	O
+normal	O
+or	O
+a	O
+raised	O
+serum	O
+thyrotrophin	B-GENE
+concentration	O
+.	O
+
+Routine	O
+isotope	O
+cystography	O
+using	O
+99M	O
+Tc	O
+sulfur	O
+colloid	O
+for	O
+detection	O
+and	O
+follow	O
+-	O
+up	O
+of	O
+vesico	O
+-	O
+ureteral	O
+reflux	O
+
+Air	O
+ion	O
+action	O
+on	O
+bacteria	O
+.	O
+
+The	O
+interpretation	O
+of	O
+antibiotic	O
+disc	O
+sensitivities	O
+.	O
+
+Following	O
+retransfusion	O
+,	O
+the	O
+affected	O
+epithelial	O
+lining	O
+appeared	O
+greatly	O
+distended	O
+over	O
+the	O
+oedematous	O
+lamina	O
+propria	O
+,	O
+with	O
+almost	O
+complete	O
+loss	O
+of	O
+structural	O
+detail	O
+.	O
+
+Characteristics	O
+of	O
+anesthesia	O
+and	O
+resuscitation	O
+in	O
+emergency	O
+lung	O
+surgery	O
+
+Tobramycin	O
+60	O
+mg	O
+did	O
+not	O
+show	O
+any	O
+remarkable	O
+effect	O
+,	O
+but	O
+dibecacin	O
+100	O
+mg	O
+produced	O
+a	O
+slight	O
+potentiating	O
+effect	O
+on	O
+the	O
+action	O
+of	O
+d	O
+-	O
+tubocurarine	O
+.	O
+
+In	O
+about	O
+one	O
+third	O
+of	O
+the	O
+cases	O
+this	O
+operation	O
+results	O
+in	O
+tonal	O
+and	O
+vocal	O
+improvement	O
+for	O
+patients	O
+suffering	O
+from	O
+progressive	O
+perceptive	O
+deafness	O
+.	O
+
+The	O
+specific	O
+electrical	O
+resistance	O
+of	O
+the	O
+cerebrospinal	O
+fluid	O
+was	O
+measured	O
+by	O
+means	O
+of	O
+conductometry	O
+in	O
+14	O
+cases	O
+of	O
+meningitis	O
+purulenta	O
+,	O
+17	O
+cases	O
+of	O
+meningitis	O
+serosa	O
+,	O
+10	O
+cases	O
+of	O
+encephalitis	O
+and	O
+in	O
+32	O
+control	O
+subjects	O
+.	O
+
+2	O
+-	O
+Chemical	O
+occlusion	O
+of	O
+vas	O
+is	O
+quite	O
+effective	O
+in	O
+producing	O
+a	O
+block	O
+in	O
+the	O
+vas	O
+deferens	O
+of	O
+dogs	O
+.	O
+
+Besides	O
+,	O
+we	O
+found	O
+in	O
+3	O
+patients	O
+increased	O
+serum	B-GENE
+immunoglobulins	I-GENE
+,	O
+chiefly	O
+IgG	B-GENE
+,	O
+as	O
+first	O
+Russe	O
+,	O
+Busey	O
+and	O
+Barbeau	O
+demonstrated	O
+in	O
+a	O
+large	O
+French	O
+-	O
+Canadian	O
+family	O
+.	O
+
+We	O
+suggest	O
+that	O
+such	O
+occlusions	O
+occurred	O
+at	O
+the	O
+time	O
+of	O
+the	O
+infarction	O
+.	O
+
+Streptococcal	O
+preparation	O
+(	O
+OK	O
+-	O
+432	O
+)	O
+,	O
+a	O
+new	O
+type	O
+of	O
+anti	O
+-	O
+cancer	O
+agent	O
+,	O
+was	O
+given	O
+to	O
+the	O
+patients	O
+with	O
+advanced	O
+cancer	O
+in	O
+combination	O
+with	O
+Mitomycin	O
+-	O
+C	O
+,	O
+5	O
+-	O
+FU	O
+and	O
+Cytosine	O
+arabinoside	O
+.	O
+
+Generally	O
+,	O
+a	O
+correlation	O
+was	O
+observed	O
+between	O
+highest	O
+concentrations	O
+of	O
+CSF	B-GENE
+immunoglobulins	I-GENE
+and	O
+degree	O
+of	O
+meningeal	O
+inflammatory	O
+response	O
+,	O
+even	O
+if	O
+this	O
+was	O
+a	O
+component	O
+of	O
+other	O
+neurological	O
+diseases	O
+.	O
+
+Experimental	O
+cardiotoxicity	O
+of	O
+adriamycin	O
+
+Muscular	O
+pathology	O
+
+Demonstration	O
+of	O
+the	O
+agent	O
+was	O
+performed	O
+from	O
+the	O
+6th	O
+to	O
+the	O
+11th	O
+day	O
+p	O
+.	O
+i	O
+.	O
+by	O
+direct	O
+microscopic	O
+methods	O
+(	O
+Stamp	O
+and	O
+auramine	O
+staining	O
+,	O
+fluorescent	O
+antibody	O
+technique	O
+)	O
+;	O
+the	O
+Coxiella	O
+content	O
+was	O
+determined	O
+by	O
+titration	O
+in	O
+embryonated	O
+hen	O
+'	O
+s	O
+eggs	O
+.	O
+
+The	O
+patients	O
+were	O
+divided	O
+into	O
+4	O
+groups	O
+receiving	O
+NLA	O
+II	O
+with	O
+or	O
+without	O
+nalorphine	O
+,	O
+morphine	O
+or	O
+Micoren	O
+.	O
+
+The	O
+alterations	O
+of	O
+5	O
+-	O
+HT	O
+and	O
+5	O
+-	O
+HIAA	O
+levels	O
+in	O
+several	O
+regions	O
+of	O
+the	O
+brain	O
+under	O
+the	O
+conditions	O
+examined	O
+may	O
+indicate	O
+that	O
+IDPN	O
+'	O
+s	O
+neurotoxicity	O
+primarily	O
+affects	O
+5	O
+-	O
+HT	O
+-	O
+containing	O
+neurones	O
+.	O
+
+(	O
+5	O
+)	O
+An	O
+increase	O
+in	O
+leukocyte	O
+-	O
+counts	O
+occurred	O
+on	O
+the	O
+administration	O
+of	O
+serum	O
+obtained	O
+from	O
+rabbit	O
+during	O
+phase	O
+-	O
+2	O
+.	O
+
+The	O
+results	O
+obtained	O
+tend	O
+to	O
+prove	O
+that	O
+the	O
+reticuloendothelial	O
+system	O
+mainly	O
+participated	O
+in	O
+beryllium	O
+retention	O
+.	O
+
+The	O
+calcium	O
+ratio	O
+(	O
+mean	O
+ratio	O
+of	O
+the	O
+predicted	O
+to	O
+measured	O
+TBCa	O
+)	O
+in	O
+men	O
+was	O
+1	O
+.	O
+000	O
++	O
+/	O
+-	O
+7	O
+.	O
+8	O
+%	O
+and	O
+in	O
+women	O
+0	O
+.	O
+996	O
++	O
+/	O
+-	O
+7	O
+.	O
+1	O
+%	O
+.	O
+
+Total	O
+cholesterol	O
+was	O
+measured	O
+in	O
+amniotic	O
+fluids	O
+collected	O
+at	O
+different	O
+stages	O
+of	O
+gestation	O
+.	O
+
+Her	O
+serum	O
+FT3	O
+concentration	O
+was	O
+,	O
+however	O
+,	O
+much	O
+higher	O
+than	O
+the	O
+ranges	O
+in	O
+normal	O
+pregnancy	O
+or	O
+in	O
+GTD	O
+patients	O
+without	O
+clinical	O
+hyperthyroidism	O
+.	O
+
+The	O
+authors	O
+found	O
+that	O
+except	O
+for	O
+fear	O
+and	O
+pugnacity	O
+all	O
+husband	O
+-	O
+wife	O
+trait	O
+correlations	O
+were	O
+positive	O
+,	O
+in	O
+contrast	O
+to	O
+Winch	O
+'	O
+s	O
+principle	O
+of	O
+type	O
+I	O
+complementarity	O
+.	O
+
+A	O
+note	O
+on	O
+the	O
+phase	O
+-	O
+plane	O
+technique	O
+representation	O
+of	O
+cardiac	O
+action	O
+potentials	O
+.	O
+
+3	O
+activities	O
+of	O
+the	O
+factor	B-GENE
+II	I-GENE
+molecule	O
+in	O
+the	O
+newborn	O
+infant	O
+at	O
+term	O
+
+However	O
+,	O
+we	O
+did	O
+detect	O
+lot	O
+-	O
+to	O
+-	O
+lot	O
+variation	O
+and	O
+differences	O
+in	O
+performance	O
+between	O
+narrow	O
+bandpass	O
+and	O
+wide	O
+bandpass	O
+spectrophotometers	O
+.	O
+
+The	O
+cochlear	O
+compromise	O
+.	O
+
+A	O
+case	O
+observed	O
+in	O
+Saigon	O
+
+Hypertonic	O
+glucose	O
+administered	O
+intrajejunally	O
+in	O
+Heidenhain	O
+pouch	O
+dogs	O
+resulted	O
+in	O
+an	O
+equal	O
+inhibition	O
+of	O
+pentagastrin	O
+-	O
+induced	O
+acid	O
+secretion	O
+from	O
+the	O
+pouch	O
+and	O
+the	O
+main	O
+stomach	O
+,	O
+whereas	O
+hypertonic	O
+saline	O
+had	O
+no	O
+effect	O
+.	O
+
+Biohydrogenation	O
+of	O
+linoleic	O
+acid	O
+into	O
+octadecenoic	O
+acid	O
+was	O
+observed	O
+.	O
+
+Chlamydial	O
+agents	O
+were	O
+isolated	O
+from	O
+the	O
+semen	O
+near	O
+the	O
+end	O
+of	O
+the	O
+chlamydemic	O
+phase	O
+.	O
+
+Because	O
+of	O
+the	O
+increased	O
+CPK	B-GENE
+activity	O
+found	O
+in	O
+normal	O
+newborns	O
+,	O
+screening	O
+for	O
+Duchenne	O
+-	O
+type	O
+muscular	O
+dystrophy	O
+should	O
+be	O
+postponed	O
+for	O
+a	O
+few	O
+weeks	O
+after	O
+delivery	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+insulin	B-GENE
+response	O
+had	O
+returned	O
+to	O
+the	O
+non	O
+-	O
+pregnant	O
+value	O
+by	O
+the	O
+second	O
+day	O
+of	O
+the	O
+puerperium	O
+.	O
+
+The	O
+authors	O
+report	O
+the	O
+results	O
+of	O
+a	O
+series	O
+of	O
+toxicological	O
+tests	O
+conducted	O
+on	O
+plastic	O
+materials	O
+(	O
+polyethylene	O
+)	O
+activated	O
+with	O
+tetraphenylbutadiene	O
+(	O
+TPB	O
+)	O
+an	O
+additive	O
+recently	O
+proposed	O
+as	O
+a	O
+sensitizer	O
+capable	O
+of	O
+photodegrading	O
+plastic	O
+materials	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+the	O
+major	O
+homology	O
+region	O
+of	O
+Mason	O
+-	O
+Pfizer	O
+monkey	O
+virus	O
+by	O
+use	O
+of	O
+saturation	O
+mutagenesis	O
+.	O
+
+One	O
+site	O
+,	O
+PAL	B-GENE
+,	O
+occurs	O
+within	O
+the	O
+10	O
+bp	O
+sequence	O
+GGGGAGGAGG	O
+.	O
+
+Nuclear	O
+extracts	O
+prepared	O
+from	O
+both	O
+neural	O
+and	O
+non	O
+-	O
+neural	O
+cell	O
+lines	O
+,	O
+mouse	O
+brain	O
+,	O
+and	O
+mouse	O
+liver	O
+contain	O
+proteins	O
+that	O
+recognize	O
+and	O
+bind	O
+to	O
+the	O
+PROX	O
+and	O
+PAL	O
+sequences	O
+indicating	O
+that	O
+proteins	O
+which	O
+bind	O
+to	O
+these	O
+target	O
+sequences	O
+are	O
+widespread	O
+.	O
+
+To	O
+determine	O
+if	O
+the	O
+NF	B-GENE
+(	I-GENE
+H	I-GENE
+)	I-GENE
+promoter	I-GENE
+can	O
+be	O
+activated	O
+in	O
+a	O
+tissue	O
+specific	O
+manner	O
+during	O
+development	O
+transgenic	O
+mice	O
+containing	O
+the	O
+promoter	O
+region	O
+linked	O
+to	O
+a	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+reporter	I-GENE
+gene	I-GENE
+were	O
+generated	O
+.	O
+
+Here	O
+we	O
+describe	O
+and	O
+map	O
+two	O
+more	O
+new	O
+genes	O
+identified	O
+as	O
+allele	O
+-	O
+specific	O
+suppressors	O
+that	O
+compensate	O
+for	O
+carboxy	O
+-	O
+terminal	O
+truncation	O
+of	O
+PET122	B-GENE
+.	O
+
+Previous	O
+studies	O
+have	O
+shown	O
+[	O
+Hisanaga	O
+,	O
+S	O
+.	O
+,	O
+Kusubata	O
+,	O
+M	O
+.	O
+,	O
+Okumura	O
+,	O
+E	O
+.	O
+&	O
+Kishimoto	O
+,	O
+T	O
+.	O
+
+Treatment	O
+and	O
+staining	O
+of	O
+smears	O
+and	O
+sections	O
+for	O
+detection	O
+of	O
+microorganisms	O
+
+The	O
+apparent	O
+Kd	O
+of	O
+the	O
+MetRS	B-GENE
+/	I-GENE
+CAU	I-GENE
+operator	I-GENE
+complex	I-GENE
+is	O
+one	O
+order	O
+magnitude	O
+higher	O
+than	O
+that	O
+of	O
+the	O
+ThrRS	B-GENE
+/	I-GENE
+CGU	I-GENE
+operator	I-GENE
+complex	I-GENE
+.	O
+
+A	O
+significant	O
+direct	O
+relationship	O
+was	O
+observed	O
+between	O
+the	O
+percent	O
+area	O
+density	O
+of	O
+smooth	O
+muscle	O
+and	O
+the	O
+percent	O
+change	O
+in	O
+peak	O
+urinary	O
+flow	O
+rate	O
+.	O
+
+Rabbit	B-GENE
+skeletal	I-GENE
+muscle	I-GENE
+glycogenin	I-GENE
+.	O
+
+Characterization	O
+of	O
+the	O
+human	B-GENE
+gene	I-GENE
+encoding	I-GENE
+cytokeratin	I-GENE
+17	I-GENE
+and	O
+its	O
+expression	O
+pattern	O
+.	O
+
+Animals	O
+that	O
+received	O
+DSP	O
+-	O
+4	O
+were	O
+significantly	O
+retarded	O
+in	O
+motor	O
+recovery	O
+compared	O
+with	O
+the	O
+saline	O
+group	O
+.	O
+
+The	O
+prophylactic	O
+use	O
+of	O
+new	O
+medication	O
+for	O
+patients	O
+between	O
+the	O
+first	O
+and	O
+second	O
+cycle	O
+of	O
+chemotherapy	O
+,	O
+in	O
+agreement	O
+with	O
+the	O
+estimates	O
+calculated	O
+,	O
+does	O
+not	O
+save	O
+health	O
+care	O
+costs	O
+but	O
+may	O
+improve	O
+the	O
+quality	O
+of	O
+life	O
+in	O
+these	O
+patients	O
+and	O
+permit	O
+the	O
+continuation	O
+of	O
+a	O
+therapeutic	O
+schedule	O
+without	O
+interruption	O
+which	O
+may	O
+improve	O
+the	O
+life	O
+expectancy	O
+of	O
+the	O
+patient	O
+.	O
+
+The	O
+isolation	O
+of	O
+this	O
+gene	O
+was	O
+based	O
+on	O
+the	O
+identification	O
+of	O
+the	O
+Y	O
+-	O
+231	O
+cosmid	O
+that	O
+contains	O
+CpG	O
+rich	O
+sequences	O
+(	O
+HTF	O
+islands	O
+)	O
+in	O
+its	O
+human	O
+insert	O
+.	O
+
+Gene	O
+constructs	O
+consisting	O
+of	O
+human	B-GENE
+growth	I-GENE
+hormone	I-GENE
+(	O
+hGH	B-GENE
+)	O
+gene	O
+driven	O
+by	O
+promoter	O
+/	O
+regulatory	O
+sequence	O
+of	O
+mouse	B-GENE
+metallothionein	I-GENE
+(	O
+mMT	B-GENE
+)	O
+,	O
+viral	B-GENE
+thymidine	I-GENE
+kinase	I-GENE
+(	O
+vTK	B-GENE
+)	O
+,	O
+rat	B-GENE
+cholecystokinin	I-GENE
+(	O
+rCCK	B-GENE
+)	O
+,	O
+or	O
+chicken	B-GENE
+beta	I-GENE
+-	I-GENE
+actin	I-GENE
+(	O
+cBA	B-GENE
+)	O
+gene	O
+were	O
+injected	O
+into	O
+the	O
+cytoplasm	O
+of	O
+fertilized	O
+medaka	O
+eggs	O
+via	O
+the	O
+micropyle	O
+.	O
+
+Serum	O
+gastrin	B-GENE
+and	O
+AFP	B-GENE
+levels	O
+had	O
+the	O
+same	O
+evolution	O
+and	O
+appear	O
+to	O
+have	O
+the	O
+same	O
+interest	O
+to	O
+follow	O
+the	O
+course	O
+of	O
+the	O
+disease	O
+.	O
+
+Prospects	O
+for	O
+controlled	O
+-	O
+delivery	O
+systems	O
+.	O
+
+Though	O
+hepatomegaly	O
+and	O
+mild	O
+elevation	O
+of	O
+enzymes	O
+can	O
+be	O
+observed	O
+in	O
+a	O
+significant	O
+proportion	O
+of	O
+patients	O
+,	O
+involvement	O
+of	O
+liver	O
+leading	O
+to	O
+acute	O
+hepatitis	O
+or	O
+liver	O
+cell	O
+necrosis	O
+is	O
+a	O
+relatively	O
+uncommon	O
+complication	O
+in	O
+P	O
+.	O
+falciparum	O
+malaria	O
+.	O
+
+For	O
+the	O
+first	O
+group	O
+,	O
+the	O
+maximal	O
+decrease	O
+in	O
+plasma	O
+potassium	O
+elicited	O
+by	O
+salbutamol	O
+was	O
+0	O
+.	O
+80	O
++	O
+/	O
+-	O
+0	O
+.	O
+19	O
+,	O
+0	O
+.	O
+48	O
++	O
+/	O
+-	O
+0	O
+.	O
+22	O
+,	O
+and	O
+0	O
+.	O
+78	O
++	O
+/	O
+-	O
+0	O
+.	O
+46	O
+mmol	O
+/	O
+l	O
+,	O
+and	O
+for	O
+the	O
+second	O
+group	O
+,	O
+maximal	O
+decrement	O
+was	O
+1	O
+.	O
+31	O
++	O
+/	O
+-	O
+0	O
+.	O
+37	O
+,	O
+0	O
+.	O
+70	O
++	O
+/	O
+-	O
+0	O
+.	O
+24	O
+,	O
+and	O
+0	O
+.	O
+84	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+mmol	O
+/	O
+l	O
+for	O
+the	O
+iv	O
+,	O
+po	O
+,	O
+and	O
+it	O
+routes	O
+,	O
+respectively	O
+.	O
+
+A	O
+statistically	O
+significant	O
+improvement	O
+due	O
+to	O
+the	O
+administration	O
+of	O
+Bromergon	O
+was	O
+observed	O
+in	O
+symptoms	O
+associated	O
+with	O
+overreactiveness	O
+to	O
+normal	O
+prolactin	B-GENE
+levels	O
+,	O
+i	O
+.	O
+e	O
+.	O
+abdominal	O
+tension	O
+,	O
+edema	O
+,	O
+weight	O
+gain	O
+and	O
+breast	O
+tenderness	O
+.	O
+
+The	O
+magnitude	O
+of	O
+the	O
+early	O
+response	O
+was	O
+241	O
++	O
+/	O
+-	O
+51	O
+%	O
+in	O
+A	O
+(	O
+%	O
+baseline	O
+RL	O
+;	O
+mean	O
++	O
+/	O
+-	O
+SE	O
+)	O
+,	O
+and	O
+significantly	O
+less	O
+in	O
+B	O
+(	O
+119	O
++	O
+/	O
+-	O
+7	O
+%	O
+)	O
+and	O
+C	O
+(	O
+131	O
++	O
+/	O
+-	O
+16	O
+%	O
+)	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Most	O
+of	O
+the	O
+patients	O
+presented	O
+with	O
+Transient	O
+Ischemic	O
+Attacks	O
+(	O
+64	O
+%	O
+)	O
+or	O
+Reversible	O
+Ischemic	O
+Neurologic	O
+Deficits	O
+(	O
+19	O
+%	O
+)	O
+.	O
+
+This	O
+analysis	O
+,	O
+together	O
+with	O
+a	O
+consideration	O
+of	O
+the	O
+SCBs	O
+found	O
+upstream	O
+of	O
+known	O
+SWI4	B-GENE
+,	I-GENE
+6	I-GENE
+-	O
+dependent	O
+genes	O
+,	O
+leads	O
+to	O
+the	O
+proposal	O
+of	O
+a	O
+revised	O
+consensus	O
+sequence	O
+for	O
+this	O
+important	O
+regulatory	O
+element	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+a	O
+DNA	O
+sequence	O
+involved	O
+in	O
+linking	O
+gene	O
+expression	O
+to	O
+the	O
+cell	O
+cycle	O
+.	O
+
+The	O
+natural	O
+history	O
+of	O
+these	O
+lesions	O
+,	O
+locoregional	O
+efficiency	O
+of	O
+the	O
+different	O
+treatments	O
+used	O
+,	O
+the	O
+part	O
+played	O
+by	O
+chemotherapy	O
+,	O
+survival	O
+,	O
+causes	O
+of	O
+death	O
+and	O
+therapeutic	O
+modalities	O
+used	O
+as	O
+a	O
+last	O
+measure	O
+,	O
+have	O
+been	O
+analysed	O
+.	O
+
+The	O
+method	O
+was	O
+adapted	O
+for	O
+the	O
+determination	O
+of	O
+nadolol	O
+racemate	O
+A	O
+by	O
+a	O
+change	O
+in	O
+mobile	O
+phase	O
+composition	O
+.	O
+
+In	O
+general	O
+,	O
+however	O
+,	O
+this	O
+study	O
+provided	O
+little	O
+evidence	O
+of	O
+any	O
+effect	O
+of	O
+supplementation	O
+to	O
+athletic	O
+performance	O
+for	O
+athletes	O
+consuming	O
+the	O
+dietary	O
+RDIs	O
+.	O
+
+In	O
+7	O
+of	O
+9	O
+cases	O
+,	O
+the	O
+enhancer	O
+is	O
+fused	O
+to	O
+the	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+bearing	I-GENE
+sequences	I-GENE
+of	O
+chromosome	O
+8	O
+.	O
+
+These	O
+components	O
+both	O
+had	O
+a	O
+median	O
+R2	O
+of	O
+0	O
+.	O
+84	O
+,	O
+compared	O
+to	O
+median	O
+R2s	O
+ranging	O
+from	O
+0	O
+.	O
+37	O
+to	O
+0	O
+.	O
+83	O
+for	O
+five	O
+commonly	O
+used	O
+ad	O
+hoc	O
+EEG	O
+components	O
+.	O
+
+The	O
+obtained	O
+results	O
+were	O
+compared	O
+with	O
+control	O
+group	O
+(	O
+10	O
+female	O
+volunteers	O
+)	O
+.	O
+
+100	O
+years	O
+of	O
+dentistry	O
+at	O
+the	O
+Friedrich	O
+Schiller	O
+University	O
+in	O
+Jena	O
+
+The	O
+target	O
+contained	O
+between	O
+positions	O
+-	O
+403	O
+and	O
+-	O
+125	O
+acts	O
+independently	O
+of	O
+orientation	O
+,	O
+in	O
+different	O
+cell	O
+types	O
+and	O
+species	O
+,	O
+and	O
+in	O
+the	O
+context	O
+of	O
+a	O
+heterologous	O
+promoter	O
+.	O
+
+Synergistic	O
+transactivation	O
+of	O
+the	O
+BMRF1	B-GENE
+promoter	I-GENE
+by	O
+the	O
+Z	B-GENE
+/	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+combination	O
+appears	O
+to	O
+involve	O
+direct	O
+binding	O
+by	O
+the	O
+Z	B-GENE
+protein	I-GENE
+but	O
+not	O
+the	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+UCR	O
+core	O
+sequence	O
+,	O
+CGCCATTTT	O
+,	O
+binds	O
+a	O
+ubiquitous	O
+nuclear	O
+factor	O
+and	O
+mediates	O
+negative	O
+regulation	O
+of	O
+MuLV	O
+promoter	O
+activity	O
+.	O
+
+These	O
+studies	O
+show	O
+that	O
+UCRBP	B-GENE
+binds	O
+to	O
+various	O
+target	O
+motifs	O
+that	O
+are	O
+distinct	O
+from	O
+the	O
+UCR	O
+motif	O
+:	O
+the	O
+adeno	B-GENE
+-	I-GENE
+associated	I-GENE
+virus	I-GENE
+P5	I-GENE
+promoter	I-GENE
+and	O
+elements	O
+in	O
+the	O
+immunoglobulin	B-GENE
+light	I-GENE
+-	I-GENE
+and	I-GENE
+heavy	I-GENE
+-	I-GENE
+chain	I-GENE
+genes	O
+,	O
+as	O
+well	O
+as	O
+elements	O
+in	O
+ribosomal	B-GENE
+protein	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+cellular	O
+sequences	O
+5	O
+'	O
+to	O
+the	O
+viral	O
+integration	O
+site	O
+exhibited	O
+85	O
+to	O
+97	O
+%	O
+identity	O
+to	O
+several	O
+sequences	O
+belonging	O
+to	O
+the	O
+mouse	B-GENE
+L1	I-GENE
+family	I-GENE
+of	O
+long	O
+interspersed	O
+repetitive	O
+sequences	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+both	O
+N	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+mutations	O
+are	O
+required	O
+to	O
+inhibit	O
+transrepression	O
+by	O
+FBR	B-GENE
+protein	I-GENE
+and	O
+that	O
+multiple	O
+structural	O
+mutations	O
+accompanied	O
+by	O
+posttranslational	O
+protein	O
+modification	O
+alter	O
+gene	O
+regulation	O
+by	O
+FBR	B-GENE
+protein	I-GENE
+.	O
+
+The	O
+JS78	O
+mutation	O
+changes	O
+Gln243	O
+in	O
+gp0	O
+.	O
+7	O
+to	O
+an	O
+amber	O
+codon	O
+,	O
+which	O
+explains	O
+the	O
+production	O
+of	O
+the	O
+truncated	O
+,	O
+30	B-GENE
+-	I-GENE
+kDa	I-GENE
+gp0	I-GENE
+.	I-GENE
+7	I-GENE
+-	I-GENE
+related	I-GENE
+polypeptide	I-GENE
+,	O
+and	O
+implicates	O
+the	O
+11	O
+-	O
+kDa	O
+C	O
+-	O
+terminal	O
+domain	O
+in	O
+host	O
+transcription	O
+shut	O
+-	O
+off	O
+.	O
+
+The	O
+predicted	O
+receptor	O
+structure	O
+includes	O
+a	O
+cysteine	O
+-	O
+rich	O
+extracellular	O
+domain	O
+,	O
+a	O
+single	O
+hydrophobic	O
+transmembrane	O
+domain	O
+,	O
+and	O
+a	O
+predicted	O
+cytoplasmic	B-GENE
+serine	I-GENE
+/	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+domain	I-GENE
+.	O
+
+Drosophila	B-GENE
+UbcD1	I-GENE
+encodes	O
+a	O
+highly	O
+conserved	O
+ubiquitin	B-GENE
+-	O
+conjugating	O
+enzyme	O
+involved	O
+in	O
+selective	O
+protein	O
+degradation	O
+.	O
+
+Analysis	O
+of	O
+the	O
+entire	O
+16	O
+.	O
+7	O
+-	O
+kb	O
+mt	O
+genome	O
+determined	O
+that	O
+a	O
+MDP1	B-GENE
+mediates	O
+cleavage	O
+of	O
+chick	O
+mtDNA	O
+in	O
+vitro	O
+at	O
+three	O
+H	O
+-	O
+and	O
+two	O
+L	O
+-	O
+strand	O
+sequence	O
+-	O
+specific	O
+target	O
+sites	O
+located	O
+within	O
+a	O
+90	O
+-	O
+bp	O
+A	O
++	O
+T	O
+-	O
+rich	O
+genomic	O
+tract	O
+,	O
+theoretically	O
+capable	O
+of	O
+forming	O
+stable	O
+secondary	O
+structures	O
+,	O
+approximately	O
+200	O
+bases	O
+upstream	O
+from	O
+the	O
+H	O
+-	O
+strand	O
+origin	O
+(	O
+OH	O
+)	O
+of	O
+replication	O
+.	O
+
+The	O
+goal	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+feasibility	O
+of	O
+retrovirus	O
+mediated	O
+expression	O
+of	O
+rp47phox	B-GENE
+in	O
+the	O
+HL60	O
+and	O
+U937	O
+human	O
+hematopoietic	O
+cell	O
+lines	O
+,	O
+and	O
+in	O
+an	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+transformed	O
+B	O
+-	O
+lymphocyte	O
+cell	O
+line	O
+(	O
+EBV	O
+-	O
+BCL	O
+)	O
+derived	O
+from	O
+a	O
+p47phox	B-GENE
+-	O
+deficient	O
+CGD	O
+patient	O
+.	O
+
+A	O
+rather	O
+similar	O
+pattern	O
+of	O
+results	O
+was	O
+obtained	O
+with	O
+respect	O
+to	O
+LMP2B	B-GENE
+mRNA	I-GENE
+expression	O
+,	O
+such	O
+transcripts	O
+being	O
+detectable	O
+only	O
+in	O
+a	O
+subset	O
+of	O
+tumors	O
+,	O
+and	O
+then	O
+at	O
+apparently	O
+low	O
+levels	O
+.	O
+
+Analysis	O
+of	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+rightmost	O
+43	O
+kbp	O
+of	O
+herpesvirus	O
+saimiri	O
+(	O
+HVS	O
+)	O
+L	O
+-	O
+DNA	O
+:	O
+general	O
+conservation	O
+of	O
+genetic	O
+organization	O
+between	O
+HVS	O
+and	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+.	O
+
+Treatment	O
+with	O
+MK	O
+-	O
+801	O
+induced	O
+a	O
+burst	O
+suppression	O
+in	O
+the	O
+EEG	O
+and	O
+a	O
+transient	O
+drop	O
+(	O
+11	O
+.	O
+4	O
++	O
+/	O
+-	O
+6	O
+.	O
+5	O
+mm	O
+Hg	O
+)	O
+in	O
+the	O
+mean	O
+arterial	O
+pressure	O
+.	O
+
+Myogenic	O
+differentiation	O
+can	O
+be	O
+inhibited	O
+by	O
+the	O
+adenovirus	O
+E1a	B-GENE
+protein	I-GENE
+in	O
+the	O
+rat	O
+L6	O
+muscle	O
+cell	O
+line	O
+.	O
+
+Acad	O
+.	O
+
+Both	O
+in	O
+vitro	O
+-	O
+synthesized	O
+S2	B-GENE
+protein	I-GENE
+and	O
+synthetic	O
+peptides	O
+corresponding	O
+to	O
+S2	B-GENE
+are	O
+shown	O
+to	O
+react	O
+positively	O
+with	O
+sera	O
+obtained	O
+from	O
+EIAV	O
+-	O
+infected	O
+horses	O
+,	O
+providing	O
+the	O
+first	O
+direct	O
+evidence	O
+of	O
+expression	O
+of	O
+this	O
+protein	O
+in	O
+infected	O
+animals	O
+.	O
+
+Many	O
+canonical	O
+TATA	O
+sequences	O
+are	O
+present	O
+upstream	O
+from	O
+these	O
+VZV	O
+transcriptional	O
+start	O
+sites	O
+but	O
+,	O
+apparently	O
+,	O
+are	O
+not	O
+used	O
+.	O
+
+The	O
+ORF	O
+4	O
+gene	O
+was	O
+minimally	O
+active	O
+,	O
+whereas	O
+the	O
+ORF	O
+62	O
+gene	O
+gave	O
+twofold	O
+induction	O
+;	O
+both	O
+genes	O
+,	O
+acting	O
+together	O
+,	O
+gave	O
+fivefold	O
+induction	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+IR5	B-GENE
+ORF	I-GENE
+of	O
+EHV	O
+-	O
+1	O
+possesses	O
+a	O
+sequence	O
+of	O
+13	O
+amino	O
+acids	O
+(	O
+CAYWCCLGHAFAC	O
+)	O
+that	O
+is	O
+a	O
+perfect	O
+match	O
+to	O
+the	O
+consensus	O
+zinc	O
+finger	O
+motif	O
+(	O
+C	O
+-	O
+X2	O
+-	O
+4	O
+-	O
+C	O
+-	O
+X2	O
+-	O
+15	O
+-	O
+C	O
+/	O
+H	O
+-	O
+X2	O
+-	O
+4	O
+-	O
+C	O
+/	O
+H	O
+)	O
+.	O
+
+The	O
+DNA	O
+sequence	O
+of	O
+the	O
+sulfate	B-GENE
+activation	I-GENE
+locus	I-GENE
+from	O
+Escherichia	O
+coli	O
+K	O
+-	O
+12	O
+has	O
+been	O
+determined	O
+.	O
+
+Plasma	O
+membranes	O
+of	O
+cultured	O
+cells	O
+contain	O
+high	O
+affinity	O
+receptors	O
+for	O
+high	B-GENE
+density	I-GENE
+lipoprotein	I-GENE
+(	O
+HDL	B-GENE
+)	O
+that	O
+appear	O
+to	O
+mediate	O
+removal	O
+of	O
+excess	O
+intracellular	O
+cholesterol	O
+.	O
+
+After	O
+the	O
+first	O
+28	O
+patients	O
+vincristine	O
+was	O
+replaced	O
+by	O
+teniposide	O
+(	O
+VM	O
+-	O
+26	O
+)	O
+due	O
+to	O
+neurotoxicity	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+an	O
+internal	O
+short	O
+element	O
+located	O
+at	O
+the	O
+very	O
+5	O
+'	O
+terminal	O
+of	O
+L1	B-GENE
+sequence	I-GENE
+and	O
+the	O
+nuclear	O
+factor	O
+binding	O
+to	O
+the	O
+element	O
+play	O
+a	O
+crucial	O
+role	O
+in	O
+the	O
+transcription	O
+of	O
+human	B-GENE
+L1	I-GENE
+.	O
+
+Tumor	O
+cells	O
+were	O
+focally	O
+immunoreactive	O
+for	O
+neuron	B-GENE
+-	I-GENE
+specific	I-GENE
+enolase	I-GENE
+,	O
+insulin	B-GENE
+,	O
+glucagon	B-GENE
+and	O
+VIP	B-GENE
+.	O
+
+A	O
+recombinant	O
+with	O
+a	O
+5	O
+'	O
+end	O
+from	O
+src	B-GENE
+and	O
+a	O
+3	O
+'	O
+end	O
+from	O
+ros	B-GENE
+,	O
+called	O
+SRC	B-GENE
+x	O
+ROS	B-GENE
+,	O
+transformed	O
+chicken	O
+embryo	O
+fibroblasts	O
+(	O
+CEF	O
+)	O
+to	O
+a	O
+spindle	O
+shape	O
+morphology	O
+,	O
+mimicking	O
+that	O
+of	O
+UR2	B-GENE
+.	O
+
+ROS	B-GENE
+x	O
+SRC	B-GENE
+(	O
+R	B-GENE
+)	O
+contains	O
+a	O
+16	O
+-	O
+amino	O
+-	O
+acid	O
+deletion	O
+that	O
+includes	O
+the	O
+3	O
+'	O
+half	O
+of	O
+the	O
+transmembrane	O
+domain	O
+of	O
+ros	B-GENE
+.	O
+
+To	O
+define	O
+the	O
+number	O
+and	O
+nature	O
+of	O
+the	O
+E6	B-GENE
+and	O
+E7	B-GENE
+gene	I-GENE
+products	O
+expressed	O
+in	O
+BPV	O
+-	O
+1	O
+-	O
+transformed	O
+cells	O
+,	O
+we	O
+performed	O
+immunoprecipitation	O
+experiments	O
+with	O
+antisera	O
+raised	O
+to	O
+bacterially	O
+expressed	O
+BPV	B-GENE
+-	I-GENE
+1	I-GENE
+E6	I-GENE
+and	O
+E7	B-GENE
+fusion	I-GENE
+proteins	I-GENE
+.	O
+
+Transient	O
+transfection	O
+assays	O
+showed	O
+that	O
+site	O
+A	O
+is	O
+necessary	O
+and	O
+sufficient	O
+for	O
+RXR	B-GENE
+alpha	I-GENE
+-	O
+mediated	O
+transactivation	O
+of	O
+the	O
+apoAI	B-GENE
+gene	I-GENE
+basal	I-GENE
+promoter	I-GENE
+in	O
+human	O
+hepatoma	O
+HepG2	O
+cells	O
+in	O
+the	O
+presence	O
+of	O
+RA	O
+and	O
+that	O
+this	O
+transactivation	O
+is	O
+abolished	O
+by	O
+increasing	O
+amounts	O
+of	O
+cotransfected	O
+ARP	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+A	O
+third	O
+prominent	O
+component	O
+of	O
+apparent	O
+molecular	O
+mass	O
+16	O
+kDa	O
+displayed	O
+several	O
+properties	O
+,	O
+including	O
+ability	O
+to	O
+bind	O
+45Ca2	O
++	O
+,	O
+that	O
+are	O
+characteristic	O
+of	O
+the	O
+regulatory	O
+(	O
+B	O
+)	O
+subunit	O
+of	O
+mammalian	B-GENE
+calcineurin	I-GENE
+and	O
+was	O
+recognized	O
+by	O
+an	O
+antiserum	O
+raised	O
+against	O
+bovine	B-GENE
+calcineurin	I-GENE
+.	O
+
+As	O
+was	O
+observed	O
+previously	O
+for	O
+MATa	B-GENE
+cna1	B-GENE
+cna2	B-GENE
+double	O
+mutants	O
+,	O
+MATa	B-GENE
+cnb1	B-GENE
+mutants	I-GENE
+were	O
+defective	O
+in	O
+their	O
+ability	O
+to	O
+recover	O
+from	O
+alpha	B-GENE
+-	I-GENE
+factor	I-GENE
+-	O
+induced	O
+growth	O
+arrest	O
+.	O
+
+Antibodies	O
+against	O
+this	O
+purified	O
+protein	O
+localize	O
+RIM1	B-GENE
+to	O
+mitochondria	O
+.	O
+
+METHODS	O
+:	O
+IgG	B-GENE
+antibodies	I-GENE
+vs	O
+HHV	O
+-	O
+6	O
+(	O
+anti	B-GENE
+-	I-GENE
+HHV	I-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+IgG	I-GENE
+)	O
+were	O
+determined	O
+by	O
+indirect	O
+immunofluorescence	O
+in	O
+100	O
+IVDA	O
+(	O
+29	O
+seronegative	O
+and	O
+71	O
+seropositive	O
+for	O
+HIV	O
+-	O
+1	O
+of	O
+which	O
+45	O
+were	O
+in	O
+stage	O
+II	O
+and	O
+26	O
+in	O
+IV	O
+-	O
+C1	O
+of	O
+CDC	O
+)	O
+as	O
+well	O
+as	O
+in	O
+100	O
+healthy	O
+subjects	O
+of	O
+a	O
+similar	O
+age	O
+(	O
+control	O
+group	O
+)	O
+.	O
+
+A	O
+position	O
+-	O
+independent	O
+activation	O
+domain	O
+which	O
+contained	O
+conserved	O
+regions	O
+II	O
+and	O
+III	O
+was	O
+identified	O
+at	O
+the	O
+carboxyl	O
+terminus	O
+of	O
+the	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+protein	I-GENE
+(	O
+amino	O
+acids	O
+361	O
+to	O
+458	O
+)	O
+.	O
+
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+amino	I-GENE
+-	I-GENE
+terminal	I-GENE
+sequences	I-GENE
+defined	O
+by	O
+conserved	O
+region	O
+IV	O
+also	O
+contributed	O
+to	O
+transactivation	O
+,	O
+but	O
+region	O
+IV	O
+activity	O
+required	O
+the	O
+participation	O
+of	O
+the	O
+region	O
+II	O
+-	O
+III	O
+domain	O
+.	O
+
+Possible	O
+roles	O
+of	O
+RAD5	B-GENE
+putative	O
+ATPase	B-GENE
+/	O
+DNA	B-GENE
+helicase	I-GENE
+activity	O
+in	O
+DNA	O
+repair	O
+and	O
+in	O
+the	O
+maintenance	O
+of	O
+wild	O
+-	O
+type	O
+rates	O
+of	O
+instability	O
+of	O
+simple	O
+repetitive	O
+sequences	O
+are	O
+discussed	O
+.	O
+
+Susceptibilities	O
+of	O
+540	O
+anaerobic	O
+gram	O
+-	O
+negative	O
+bacilli	O
+to	O
+amoxicillin	O
+,	O
+amoxicillin	O
+-	O
+BRL	O
+42715	O
+,	O
+amoxicillin	O
+-	O
+clavulanate	O
+,	O
+temafloxacin	O
+,	O
+and	O
+clindamycin	O
+.	O
+
+Nocodazole	O
+arrest	O
+of	O
+DU249	O
+cells	O
+was	O
+exploited	O
+for	O
+the	O
+detection	O
+of	O
+an	O
+M	O
+-	O
+phase	O
+-	O
+activated	O
+MBP	B-GENE
+kinase	I-GENE
+that	O
+was	O
+resolved	O
+from	O
+p41	B-GENE
+MAP	I-GENE
+kinase	I-GENE
+by	O
+phenyl	O
+-	O
+Superose	O
+chromatography	O
+.	O
+
+The	O
+hit1	B-GENE
+-	I-GENE
+1	I-GENE
+mutation	O
+caused	O
+a	O
+defect	O
+in	O
+synthesis	O
+of	O
+a	O
+74	B-GENE
+-	I-GENE
+kD	I-GENE
+heat	I-GENE
+shock	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+319	O
+base	O
+pair	O
+region	O
+immediately	O
+upstream	O
+of	O
+the	O
+CAP	O
+site	O
+is	O
+characterized	O
+by	O
+the	O
+lack	O
+of	O
+a	O
+proximal	O
+TATA	O
+box	O
+and	O
+the	O
+presence	O
+of	O
+sequences	O
+similar	O
+to	O
+GC	O
+boxes	O
+,	O
+CACCC	O
+boxes	O
+,	O
+CCAAT	O
+boxes	O
+,	O
+activator	B-GENE
+protein	I-GENE
+2	I-GENE
+(	O
+Ap	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+sites	O
+,	O
+partial	O
+glucocorticoid	O
+response	O
+elements	O
+(	O
+GREs	O
+)	O
+,	O
+and	O
+partial	O
+cyclic	O
+AMP	O
+response	O
+elements	O
+(	O
+CREs	O
+)	O
+.	O
+
+In	O
+rats	O
+anaesthetized	O
+with	O
++	O
+-	O
+chloralose	O
+the	O
+changes	O
+in	O
+extracellular	O
+pH	O
+and	O
+K	O
++	O
+in	O
+spinal	O
+cord	O
+dorsal	O
+horn	O
+were	O
+studied	O
+using	O
+pH	O
+and	O
+K	O
++	O
+ion	O
+-	O
+selective	O
+electrodes	O
+.	O
+
+Replication	O
+of	O
+bovine	O
+papillomavirus	O
+-	O
+1	O
+(	O
+BPV	O
+-	O
+1	O
+)	O
+DNA	O
+requires	O
+two	O
+viral	O
+gene	O
+products	O
+,	O
+the	O
+E1	B-GENE
+protein	I-GENE
+and	O
+the	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+E2	I-GENE
+protein	I-GENE
+.	O
+
+Insertional	O
+inactivation	O
+of	O
+sms	B-GENE
+led	O
+to	O
+increased	O
+sensitivity	O
+to	O
+the	O
+alkylating	O
+agent	O
+methylmethane	O
+sulfonate	O
+,	O
+but	O
+not	O
+to	O
+a	O
+requirement	O
+for	O
+serine	O
+or	O
+other	O
+metabolites	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+the	O
+MAP	B-GENE
+kinase	I-GENE
+activator	I-GENE
+/	O
+MAP	B-GENE
+kinase	I-GENE
+system	O
+may	O
+be	O
+the	O
+downstream	O
+components	O
+of	O
+ras	B-GENE
+signal	O
+transduction	O
+pathways	O
+.	O
+
+NSCL	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+expressed	O
+in	O
+a	O
+larger	O
+number	O
+of	O
+these	O
+cell	O
+lines	O
+.	O
+
+Labile	O
+LTR	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+appear	O
+to	O
+be	O
+essential	O
+for	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+hyperexpression	O
+,	O
+since	O
+both	O
+LTR	O
+-	O
+enhanced	O
+transcription	O
+and	O
+the	O
+activities	O
+of	O
+LTR	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+are	O
+specifically	O
+decreased	O
+after	O
+inhibition	O
+of	O
+protein	O
+synthesis	O
+(	O
+A	O
+.	O
+
+Ruddell	O
+,	O
+M	O
+.	O
+
+A	O
+single	O
+MEF	B-GENE
+-	I-GENE
+2	I-GENE
+site	I-GENE
+is	O
+a	O
+major	O
+positive	O
+regulatory	O
+element	O
+required	O
+for	O
+transcription	O
+of	O
+the	O
+muscle	O
+-	O
+specific	O
+subunit	O
+of	O
+the	O
+human	B-GENE
+phosphoglycerate	I-GENE
+mutase	I-GENE
+gene	I-GENE
+in	O
+skeletal	O
+and	O
+cardiac	O
+muscle	O
+cells	O
+.	O
+
+Truncation	O
+variants	O
+of	O
+peptides	O
+isolated	O
+from	O
+MHC	B-GENE
+class	I-GENE
+II	I-GENE
+molecules	I-GENE
+suggest	O
+sequence	O
+motifs	O
+.	O
+
+Although	O
+the	O
+E	O
+-	O
+box	O
+consensus	O
+is	O
+minimally	O
+defined	O
+as	O
+CANNTG	O
+,	O
+the	O
+adjacent	O
+nucleotides	O
+of	O
+functional	O
+E	O
+-	O
+boxes	O
+are	O
+variable	O
+for	O
+genes	O
+regulated	O
+by	O
+the	O
+bHLH	B-GENE
+proteins	I-GENE
+.	O
+
+Intermediate	O
+levels	O
+of	O
+gene	O
+activity	O
+were	O
+observed	O
+for	O
+TnI	B-GENE
+enhancers	I-GENE
+containing	O
+E	O
+-	O
+boxes	O
+derived	O
+from	O
+the	O
+MCK	B-GENE
+left	I-GENE
+E	I-GENE
+-	I-GENE
+box	I-GENE
+site	I-GENE
+or	O
+from	O
+the	O
+Ig	B-GENE
+kappa	I-GENE
+E2	I-GENE
+E	I-GENE
+-	I-GENE
+box	I-GENE
+.	O
+
+T	B-GENE
+-	I-GENE
+cell	I-GENE
+receptor	I-GENE
+beta	I-GENE
+(	O
+TCR	B-GENE
+beta	I-GENE
+)	O
+gene	O
+rearrangements	O
+occur	O
+in	O
+a	O
+third	O
+of	O
+early	O
+B	O
+-	O
+cell	O
+acute	O
+lymphoblastic	O
+leukemias	O
+(	O
+ALLs	O
+)	O
+.	O
+
+The	O
+CANNTG	O
+motifs	O
+were	O
+found	O
+to	O
+bind	O
+MyoD	B-GENE
+and	O
+myogenin	B-GENE
+fusion	I-GENE
+proteins	I-GENE
+and	O
+to	O
+interact	O
+with	O
+proteins	O
+in	O
+nuclear	O
+extracts	O
+from	O
+cultured	O
+myotubes	O
+.	O
+
+Peripheral	O
+polyneuropathy	O
+associated	O
+with	O
+multiple	O
+myeloma	O
+.	O
+
+We	O
+have	O
+cloned	O
+and	O
+sequenced	O
+COX12	B-GENE
+,	O
+the	O
+nuclear	O
+gene	O
+for	O
+subunit	B-GENE
+VIb	I-GENE
+of	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+cytochrome	I-GENE
+c	I-GENE
+oxidase	I-GENE
+.	O
+
+The	O
+structure	O
+of	O
+the	O
+calcineurin	B-GENE
+A	I-GENE
+gene	I-GENE
+was	O
+determined	O
+by	O
+comparison	O
+of	O
+the	O
+genomic	O
+and	O
+cDNA	O
+sequences	O
+.	O
+
+The	O
+basal	O
+promoter	O
+elements	O
+of	O
+murine	B-GENE
+cytochrome	I-GENE
+c	I-GENE
+oxidase	I-GENE
+subunit	I-GENE
+IV	I-GENE
+gene	I-GENE
+consist	O
+of	O
+tandemly	O
+duplicated	O
+ets	B-GENE
+motifs	O
+that	O
+bind	O
+to	O
+GABP	B-GENE
+-	I-GENE
+related	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+Lastly	O
+,	O
+there	O
+are	O
+multiple	O
+instances	O
+in	O
+which	O
+short	O
+oligonucleotide	O
+direct	O
+repeats	O
+flank	O
+a	O
+region	O
+absent	O
+from	O
+either	O
+variola	O
+or	O
+vaccinia	O
+virus	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+short	O
+synthetic	O
+peptides	O
+containing	O
+the	O
+pRB	B-GENE
+-	I-GENE
+binding	I-GENE
+sequences	I-GENE
+of	O
+E1A	B-GENE
+are	O
+sufficient	O
+for	O
+interaction	O
+with	O
+p107	B-GENE
+,	O
+cyclin	B-GENE
+A	I-GENE
+,	O
+and	O
+p130	B-GENE
+.	O
+
+These	O
+mutants	O
+grow	O
+normally	O
+in	O
+3T6	O
+mouse	O
+fibroblast	O
+cells	O
+,	O
+and	O
+they	O
+do	O
+not	O
+complement	O
+the	O
+wild	O
+-	O
+type	O
+virus	O
+in	O
+coinfection	O
+experiments	O
+of	O
+C2	O
+myoblasts	O
+.	O
+
+The	O
+MICs	O
+of	O
+this	O
+compound	O
+against	O
+90	O
+%	O
+of	O
+these	O
+organisms	O
+,	O
+except	O
+for	O
+methicillin	O
+-	O
+resistant	O
+S	O
+.	O
+aureus	O
+,	O
+ranged	O
+from	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+0	O
+.	O
+006	O
+to	O
+3	O
+.	O
+13	O
+micrograms	O
+/	O
+ml	O
+.	O
+
+The	O
+minimal	O
+promoter	O
+of	O
+the	O
+RII	B-GENE
+beta	I-GENE
+gene	I-GENE
+was	O
+composed	O
+of	O
+two	O
+adjacent	O
+functional	O
+elements	O
+.	O
+
+Mapping	O
+the	O
+cAMP	B-GENE
+receptor	I-GENE
+protein	I-GENE
+contact	I-GENE
+site	I-GENE
+on	O
+the	O
+alpha	O
+subunit	O
+of	O
+Escherichia	B-GENE
+coli	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+or	O
+platelet	B-GENE
+-	I-GENE
+derived	I-GENE
+growth	I-GENE
+factor	I-GENE
+stimulation	O
+of	O
+intact	O
+human	O
+or	O
+murine	O
+cells	O
+leads	O
+to	O
+phosphorylation	O
+of	O
+Nck	B-GENE
+protein	I-GENE
+on	O
+tyrosine	O
+,	O
+serine	O
+,	O
+and	O
+threonine	O
+residues	O
+.	O
+
+A	O
+major	O
+mechanism	O
+whereby	O
+steroid	B-GENE
+hydroxylase	I-GENE
+gene	I-GENE
+transcription	O
+is	O
+regulated	O
+in	O
+the	O
+adrenal	O
+cortex	O
+requires	O
+the	O
+pituitary	O
+peptide	O
+hormone	O
+,	O
+ACTH	B-GENE
+,	O
+which	O
+acts	O
+via	O
+cAMP	O
+.	O
+
+A	O
+combination	O
+of	O
+comparative	O
+sequence	O
+analysis	O
+and	O
+thermodynamic	O
+methods	O
+reveals	O
+the	O
+conservation	O
+of	O
+tertiary	O
+structure	O
+elements	O
+in	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+(	O
+UTR	O
+)	O
+of	O
+human	O
+enteroviruses	O
+and	O
+rhinoviruses	O
+.	O
+
+Km	O
+and	O
+Vmax	O
+for	O
+two	O
+substrates	O
+,	O
+src	B-GENE
+-	I-GENE
+related	I-GENE
+peptide	I-GENE
+and	O
+poly	O
+(	O
+Glu	O
+,	O
+Tyr	O
+)	O
+(	O
+4	O
+:	O
+1	O
+)	O
+,	O
+were	O
+2	O
+.	O
+4	O
+mM	O
+and	O
+2	O
+.	O
+5	O
+mumol	O
+min	O
+-	O
+1	O
+mg	O
+-	O
+1	O
+and	O
+0	O
+.	O
+26	O
+mM	O
+and	O
+1	O
+.	O
+2	O
+mumol	O
+min	O
+-	O
+1	O
+mg	O
+-	O
+1	O
+,	O
+respectively	O
+.	O
+
+Strategies	O
+for	O
+blood	O
+screening	O
+for	O
+the	O
+hepatitis	O
+C	O
+virus	O
+and	O
+for	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+in	O
+high	O
+risk	O
+groups	O
+.	O
+
+Comparison	O
+of	O
+data	O
+obtained	O
+with	O
+the	O
+results	O
+of	O
+chronic	O
+treatment	O
+with	O
+the	O
+opioid	O
+antagonist	O
+permits	O
+to	O
+conclude	O
+that	O
+the	O
+chronic	O
+blockade	O
+increases	O
+the	O
+fatiguability	O
+to	O
+a	O
+great	O
+extent	O
+than	O
+chronic	O
+activation	O
+of	O
+opioid	O
+system	O
+.	O
+
+Laboratory	O
+studies	O
+using	O
+Ca45	O
+labeled	O
+teeth	O
+and	O
+biologically	O
+stained	O
+teeth	O
+confirmed	O
+that	O
+the	O
+dentifrice	O
+did	O
+not	O
+decalcify	O
+enamel	O
+or	O
+bleach	O
+teeth	O
+.	O
+
+Structure	O
+and	O
+expression	O
+of	O
+a	O
+gene	O
+from	O
+Arabidopsis	O
+thaliana	O
+encoding	O
+a	O
+protein	O
+related	O
+to	O
+SNF1	B-GENE
+protein	O
+kinase	O
+.	O
+
+We	O
+have	O
+cloned	O
+and	O
+characterized	O
+a	O
+55	O
+-	O
+kb	O
+region	O
+of	O
+DNA	O
+surrounding	O
+HRAS1	B-GENE
+.	O
+
+The	O
+ORF1	O
+protein	O
+was	O
+found	O
+to	O
+be	O
+highly	O
+homologous	O
+to	O
+the	O
+putative	O
+potexvirus	B-GENE
+RNA	I-GENE
+replicases	I-GENE
+;	O
+ORF2	O
+,	O
+-	O
+3	O
+,	O
+-	O
+5	O
+and	O
+-	O
+6	O
+proteins	O
+also	O
+have	O
+analogues	O
+among	O
+the	O
+potex	O
+-	O
+and	O
+/	O
+or	O
+carlavirus	O
+-	O
+encoded	O
+proteins	O
+.	O
+
+A	O
+total	O
+of	O
+281	O
+patients	O
+were	O
+divided	O
+into	O
+groups	O
+according	O
+to	O
+their	O
+clinical	O
+diagnosis	O
+and	O
+were	O
+examined	O
+using	O
+capnography	O
+,	O
+spirometry	O
+and	O
+blood	O
+-	O
+gas	O
+analysis	O
+.	O
+
+The	O
+relationships	O
+between	O
+the	O
+partial	O
+pressures	O
+of	O
+O2	O
+and	O
+CO2	O
+as	O
+well	O
+as	O
+between	O
+their	O
+gradients	O
+,	O
+become	O
+stronger	O
+with	O
+the	O
+increase	O
+of	O
+the	O
+ventilation	O
+-	O
+perfusion	O
+ratio	O
+.	O
+
+No	O
+significant	O
+correlations	O
+of	O
+peak	O
+VO2	O
+were	O
+observed	O
+between	O
+the	O
+3	O
+tests	O
+.	O
+
+An	O
+RNA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+gene	I-GENE
+(	O
+rbp1	B-GENE
+)	O
+from	O
+Drosophila	O
+melanogaster	O
+,	O
+encoding	O
+an	O
+RNA	O
+recognition	O
+motif	O
+and	O
+an	O
+Arg	O
+-	O
+Ser	O
+rich	O
+(	O
+RS	O
+)	O
+domain	O
+,	O
+has	O
+been	O
+characterized	O
+.	O
+
+A	O
+comparative	O
+study	O
+of	O
+the	O
+total	O
+protein	O
+profiles	O
+of	O
+wild	O
+-	O
+type	O
+S	O
+.	O
+entomophila	O
+UC9	O
+and	O
+mutant	O
+UC21	O
+revealed	O
+that	O
+the	O
+mutant	O
+lacked	O
+an	O
+approximately	O
+44	O
+-	O
+kDa	O
+protein	O
+and	O
+overexpressed	O
+an	O
+approximately	O
+20	O
+-	O
+kDa	O
+protein	O
+.	O
+
+Characterization	O
+of	O
+the	O
+regulon	O
+controlled	O
+by	O
+the	O
+leucine	B-GENE
+-	I-GENE
+responsive	I-GENE
+regulatory	I-GENE
+protein	I-GENE
+in	O
+Escherichia	O
+coli	O
+.	O
+
+Mapping	O
+of	O
+the	O
+mouse	B-GENE
+ornithine	I-GENE
+decarboxylase	I-GENE
+-	I-GENE
+related	I-GENE
+sequence	I-GENE
+family	I-GENE
+.	O
+
+This	O
+mutation	O
+also	O
+results	O
+in	O
+markedly	O
+decreased	O
+levels	O
+of	O
+CAD	B-GENE
+mRNA	I-GENE
+and	O
+protein	O
+in	O
+the	O
+mutant	O
+.	O
+
+Mutational	O
+studies	O
+revealed	O
+that	O
+it	O
+was	O
+the	O
+homeodomain	B-GENE
+binding	I-GENE
+site	I-GENE
+II	I-GENE
+sequence	I-GENE
+that	O
+was	O
+required	O
+for	O
+this	O
+regulation	O
+.	O
+
+Thus	O
+,	O
+the	O
+pol	B-GENE
+alpha	I-GENE
+-	O
+primase	B-GENE
+complex	O
+appears	O
+to	O
+act	O
+processively	O
+for	O
+only	O
+a	O
+short	O
+distance	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+positions	O
+of	O
+these	O
+introns	O
+have	O
+been	O
+conserved	O
+in	O
+comparison	O
+with	O
+the	O
+genes	O
+of	O
+two	O
+other	O
+transglutaminase	O
+-	O
+like	O
+activities	O
+described	O
+in	O
+the	O
+literature	O
+,	O
+but	O
+the	O
+TGM1	B-GENE
+gene	I-GENE
+is	O
+by	O
+far	O
+the	O
+smallest	O
+characterized	O
+to	O
+date	O
+because	O
+its	O
+introns	O
+are	O
+relatively	O
+smaller	O
+.	O
+
+In	O
+a	O
+retrospective	O
+analysis	O
+of	O
+data	O
+from	O
+35	O
+cases	O
+with	O
+malignant	O
+lymphoma	O
+from	O
+a	O
+cohort	O
+of	O
+2017	O
+HIV	O
+-	O
+infected	O
+patients	O
+,	O
+the	O
+stage	O
+of	O
+HIV	O
+-	O
+disease	O
+,	O
+the	O
+CD4	B-GENE
+counts	O
+at	O
+the	O
+time	O
+of	O
+diagnosis	O
+,	O
+and	O
+the	O
+use	O
+of	O
+antineoplastic	O
+agents	O
+or	O
+radiotherapy	O
+were	O
+correlated	O
+with	O
+outcome	O
+.	O
+
+1	O
+.	O
+
+Effects	O
+of	O
+dioxins	O
+on	O
+thyroid	O
+function	O
+in	O
+newborn	O
+babies	O
+.	O
+
+cDNA	O
+clones	O
+encoding	O
+Arabidopsis	O
+thaliana	O
+and	O
+Zea	B-GENE
+mays	I-GENE
+mitochondrial	I-GENE
+chaperonin	I-GENE
+HSP60	B-GENE
+and	O
+gene	O
+expression	O
+during	O
+seed	O
+germination	O
+and	O
+heat	O
+shock	O
+.	O
+
+The	O
+single	O
+site	O
+of	O
+glycosylation	O
+is	O
+located	O
+near	O
+the	O
+C	O
+-	O
+terminus	O
+in	O
+the	O
+N	O
+-	O
+glycosylation	O
+sequon	O
+-	O
+Asn	O
+-	O
+Cys	O
+-	O
+Ser	O
+-	O
+in	O
+which	O
+Cys	O
+forms	O
+part	O
+of	O
+a	O
+disulphide	O
+bridge	O
+.	O
+
+The	O
+pulmonary	O
+toxic	O
+events	O
+induced	O
+by	O
+acute	O
+nitrogen	O
+dioxide	O
+(	O
+NO	O
+)	O
+2	O
+exposure	O
+were	O
+studied	O
+in	O
+the	O
+rat	O
+to	O
+develop	O
+an	O
+inhalation	O
+model	O
+to	O
+investigate	O
+therapeutic	O
+measures	O
+.	O
+
+The	O
+pulmonary	O
+effects	O
+observed	O
+,	O
+became	O
+more	O
+pronounced	O
+with	O
+increasing	O
+NO2	O
+concentrations	O
+(	O
+0	O
+,	O
+25	O
+,	O
+75	O
+,	O
+125	O
+,	O
+175	O
+or	O
+200	O
+ppm	O
+,	O
+1	O
+ppm	O
+NO2	O
+=	O
+1	O
+.	O
+88	O
+mg	O
+m	O
+-	O
+3	O
+NO2	O
+)	O
+and	O
+exposure	O
+times	O
+(	O
+5	O
+,	O
+10	O
+,	O
+20	O
+or	O
+30	O
+min	O
+)	O
+.	O
+
+Interaction	O
+of	O
+H	B-GENE
+-	I-GENE
+2Eb	I-GENE
+with	O
+an	O
+IAP	B-GENE
+retrotransposon	I-GENE
+in	O
+the	O
+A20	O
+/	O
+2J	O
+B	O
+cell	O
+lymphoma	O
+.	O
+
+Gestational	O
+trophoblastic	O
+diseases	O
+:	O
+recent	O
+advances	O
+in	O
+the	O
+understanding	O
+of	O
+cytogenetics	O
+,	O
+histopathology	O
+,	O
+and	O
+natural	O
+history	O
+.	O
+
+With	O
+the	O
+exception	O
+of	O
+mutants	O
+that	O
+remove	O
+the	O
+membrane	O
+anchor	O
+domain	O
+,	O
+all	O
+of	O
+the	O
+mutant	O
+glycoproteins	O
+retained	O
+the	O
+ability	O
+to	O
+cause	O
+fusion	O
+of	O
+CD4	B-GENE
+-	O
+bearing	O
+cells	O
+.	O
+
+The	O
+subunit	O
+protein	O
+of	O
+curli	B-GENE
+was	O
+highly	O
+homologous	O
+at	O
+its	O
+amino	O
+terminus	O
+to	O
+SEF	B-GENE
+-	I-GENE
+17	I-GENE
+,	O
+the	O
+subunit	O
+protein	O
+of	O
+thin	O
+,	O
+aggregative	O
+fimbriae	O
+of	O
+Salmonella	O
+enteritidis	O
+27655	O
+strain	O
+3b	O
+,	O
+suggesting	O
+that	O
+these	O
+fibres	O
+form	O
+a	O
+novel	O
+class	O
+of	O
+surface	O
+organelles	O
+on	O
+enterobacteria	O
+.	O
+
+Substitution	O
+of	O
+the	O
+DR1	B-GENE
+beta	I-GENE
+chain	I-GENE
+with	O
+H	B-GENE
+-	I-GENE
+2E	I-GENE
+beta	I-GENE
+k	I-GENE
+led	O
+to	O
+a	O
+dramatic	O
+loss	O
+of	O
+recognition	O
+;	O
+alpha	O
+chain	O
+substitution	O
+had	O
+a	O
+less	O
+marked	O
+effect	O
+.	O
+
+This	O
+negative	O
+regulatory	O
+pathway	O
+may	O
+be	O
+important	O
+for	O
+determining	O
+cell	O
+fate	O
+or	O
+maintaining	O
+an	O
+inducible	O
+state	O
+in	O
+the	O
+ventroposterior	O
+region	O
+of	O
+the	O
+embryo	O
+.	O
+
+The	O
+distal	O
+portion	O
+of	O
+the	O
+rat	B-GENE
+insulin	I-GENE
+I	I-GENE
+gene	I-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+flanking	I-GENE
+DNA	I-GENE
+contains	O
+two	O
+sequence	O
+elements	O
+,	O
+the	O
+Far	O
+and	O
+FLAT	O
+elements	O
+,	O
+that	O
+can	O
+function	O
+in	O
+combination	O
+,	O
+but	O
+not	O
+separately	O
+,	O
+as	O
+a	O
+beta	O
+-	O
+cell	O
+-	O
+specific	O
+transcriptional	O
+enhancer	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+exhibited	O
+98	O
+%	O
+identity	O
+to	O
+the	O
+human	O
+cellular	O
+transglutaminase	O
+sequence	O
+.	O
+
+Repeated	O
+efforts	O
+to	O
+isolate	O
+recombinant	O
+baculoviruses	O
+containing	O
+a	O
+wild	O
+-	O
+type	O
+kinase	O
+failed	O
+,	O
+whereas	O
+recombinants	O
+expressing	O
+a	O
+nonfunctional	O
+kinase	O
+with	O
+a	O
+catalytic	O
+domain	O
+II	O
+mutation	O
+were	O
+readily	O
+isolated	O
+.	O
+
+Finally	O
+,	O
+we	O
+determined	O
+that	O
+the	O
+P68	B-GENE
+amino	O
+terminus	O
+was	O
+both	O
+necessary	O
+and	O
+sufficient	O
+for	O
+binding	O
+dsRNA	O
+as	O
+we	O
+were	O
+able	O
+to	O
+transfer	O
+dsRNA	O
+-	O
+binding	O
+properties	O
+to	O
+a	O
+reporter	O
+gene	O
+product	O
+previously	O
+unable	O
+to	O
+bind	O
+RNA	O
+.	O
+
+From	O
+August	O
+1989	O
+to	O
+October	O
+1990	O
+,	O
+83	O
+pregnant	O
+Chinese	O
+women	O
+were	O
+the	O
+subjects	O
+for	O
+measuring	O
+the	O
+levels	O
+of	O
+plasma	O
+functional	O
+antithrombin	B-GENE
+III	I-GENE
+(	O
+AT	B-GENE
+III	I-GENE
+)	O
+activity	O
+.	O
+
+Visual	O
+acuity	O
+may	O
+be	O
+decreased	O
+by	O
+transient	O
+changes	O
+in	O
+refractive	O
+error	O
+caused	O
+by	O
+sulfonamides	O
+,	O
+the	O
+antifungal	O
+agent	O
+metronidazole	O
+,	O
+thiazide	O
+diuretics	O
+,	O
+and	O
+carbonic	B-GENE
+anhydrase	I-GENE
+inhibitors	O
+.	O
+
+Currents	O
+aspects	O
+of	O
+H2	B-GENE
+receptor	I-GENE
+antagonists	O
+in	O
+the	O
+treatment	O
+of	O
+ulcers	O
+
+In	O
+addition	O
+,	O
+a	O
+21	O
+-	O
+mer	O
+subrepeat	O
+structure	O
+is	O
+also	O
+present	O
+in	O
+each	O
+unit	O
+.	O
+
+Sequencing	O
+revealed	O
+one	O
+large	O
+open	O
+reading	O
+frame	O
+encoding	O
+a	O
+39	O
+-	O
+kDa	O
+protein	O
+.	O
+
+These	O
+sites	O
+are	O
+also	O
+potential	O
+keratan	O
+sulfate	O
+attachment	O
+sites	O
+.	O
+
+We	O
+propose	O
+that	O
+plasmids	O
+of	O
+the	O
+pLS1	O
+family	O
+(	O
+pE194	O
+,	O
+pADB201	O
+,	O
+and	O
+pLB4	O
+)	O
+share	O
+functional	O
+and	O
+structural	O
+characteristics	O
+for	O
+the	O
+regulation	O
+of	O
+their	O
+copy	O
+numbers	O
+.	O
+
+Perturbation	O
+of	O
+dNTP	O
+pools	O
+also	O
+affected	O
+the	O
+frameshift	O
+fidelity	O
+of	O
+the	O
+replicative	O
+yeast	B-GENE
+DNA	I-GENE
+polymerase	I-GENE
+alpha	I-GENE
+.	O
+
+Differential	O
+expression	O
+of	O
+the	O
+"	O
+B	O
+"	O
+subunit	O
+of	O
+the	O
+vacuolar	B-GENE
+H	I-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+ATPase	I-GENE
+in	O
+bovine	O
+tissues	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+hGCSFR	B-GENE
+gene	I-GENE
+was	O
+chromosomally	O
+localized	O
+by	O
+Southern	O
+blot	O
+analysis	O
+of	O
+its	O
+segregation	O
+pattern	O
+in	O
+a	O
+panel	O
+of	O
+rodent	O
+-	O
+human	O
+hybrid	O
+DNAs	O
+using	O
+the	O
+radiolabeled	O
+cDNA	O
+probe	O
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+characterised	O
+a	O
+differentially	O
+-	O
+regulated	O
+gene	O
+family	O
+in	O
+the	O
+protozoan	O
+parasite	O
+Leishmania	O
+major	O
+.	O
+
+At	O
+some	O
+sites	O
+,	O
+%	O
+T	O
+is	O
+greatly	O
+increased	O
+by	O
+Cl	O
+-	O
+concentrations	O
+up	O
+to	O
+1	O
+M	O
+,	O
+while	O
+at	O
+other	O
+sites	O
+%	O
+T	O
+is	O
+reduced	O
+or	O
+unaffected	O
+by	O
+these	O
+conditions	O
+.	O
+
+Necrosis	O
+appears	O
+6	O
+h	O
+after	O
+TA	O
+infusion	O
+,	O
+being	O
+5	O
+.	O
+77	O
+%	O
+in	O
+extent	O
+after	O
+12	O
+h	O
+,	O
+14	O
+.	O
+9	O
+%	O
+after	O
+24	O
+h	O
+and	O
+animals	O
+die	O
+with	O
+an	O
+area	O
+of	O
+29	O
+.	O
+5	O
+%	O
+necrosis	O
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+segments	O
+of	O
+C3	B-GENE
+represented	O
+by	O
+amino	O
+acid	O
+residues	O
+1082	O
+-	O
+1118	O
+,	O
+1117	O
+-	O
+1155	O
+,	O
+1234	O
+-	O
+1294	O
+and	O
+1312	O
+-	O
+1404	O
+accommodate	O
+C3	B-GENE
+(	I-GENE
+D	I-GENE
+)	I-GENE
+epitopes	I-GENE
+that	O
+are	O
+expressed	O
+by	O
+erythrocyte	O
+-	O
+bound	O
+C3	B-GENE
+fragments	I-GENE
+,	O
+but	O
+not	O
+by	O
+the	O
+corresponding	O
+fluid	O
+-	O
+phase	O
+fragment	O
+,	O
+whereas	O
+the	O
+segments	O
+spanning	O
+residues	O
+973	O
+-	O
+1026	O
+and	O
+1477	O
+-	O
+1510	O
+contain	O
+C3	B-GENE
+(	I-GENE
+D	I-GENE
+)	I-GENE
+epitopes	I-GENE
+that	O
+are	O
+exposed	O
+exclusively	O
+in	O
+denatured	O
+C3	B-GENE
+and	O
+therefore	O
+hidden	O
+in	O
+physiological	O
+fragments	O
+of	O
+the	O
+protein	O
+.	O
+
+These	O
+exons	O
+,	O
+further	O
+identified	O
+as	O
+exons	O
+9	O
+,	O
+10	O
+,	O
+and	O
+11	O
+,	O
+together	O
+encode	O
+the	O
+37	O
+amino	O
+acid	O
+residues	O
+present	O
+in	O
+alpha	B-GENE
+s1	I-GENE
+-	I-GENE
+casein	I-GENE
+variant	I-GENE
+A	I-GENE
+but	O
+missing	O
+in	O
+variant	O
+F	O
+.	O
+
+We	O
+also	O
+report	O
+here	O
+the	O
+complete	O
+structural	O
+organization	O
+of	O
+the	O
+goat	B-GENE
+alpha	I-GENE
+s1	I-GENE
+-	I-GENE
+casein	I-GENE
+transcription	I-GENE
+unit	I-GENE
+,	O
+deduced	O
+from	O
+polymerase	O
+chain	O
+reaction	O
+experiments	O
+.	O
+
+Homodimers	O
+of	O
+the	O
+three	O
+proteins	O
+specifically	O
+recognize	O
+the	O
+G	O
+-	O
+box	O
+motif	O
+,	O
+with	O
+GBF1	B-GENE
+and	O
+GBF3	B-GENE
+binding	O
+symmetrically	O
+to	O
+this	O
+palindromic	O
+sequence	O
+.	O
+
+The	O
+hydrophobicity	O
+plot	O
+of	O
+NHE	B-GENE
+-	I-GENE
+3	I-GENE
+is	O
+very	O
+similar	O
+to	O
+that	O
+of	O
+NHE	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+NHE	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+The	O
+initial	O
+translation	O
+protein	O
+encoded	O
+by	O
+the	O
+cDNA	O
+is	O
+53	O
+,	O
+932	O
+kDa	O
+and	O
+possesses	O
+a	O
+hydrophilic	O
+amino	O
+acid	O
+composition	O
+with	O
+glutamic	O
+acid	O
+comprising	O
+22	O
+%	O
+of	O
+the	O
+total	O
+amino	O
+acid	O
+residues	O
+.	O
+
+Each	O
+group	O
+received	O
+15	O
+ml	O
+/	O
+kg	O
+of	O
+either	O
+6	O
+%	O
+pentafraction	O
+,	O
+6	O
+%	O
+pentastarch	O
+,	O
+or	O
+plasma	O
+followed	O
+two	O
+hours	O
+later	O
+by	O
+1	O
+.	O
+5	O
+micrograms	O
+/	O
+kg	O
+/	O
+0	O
+.	O
+5	O
+hr	O
+E	O
+.	O
+
+Genetic	O
+and	O
+biochemical	O
+evidence	O
+suggests	O
+that	O
+v	B-GENE
+-	I-GENE
+Crk	I-GENE
+can	O
+induce	O
+transformation	O
+of	O
+chicken	O
+embryo	O
+fibroblasts	O
+by	O
+influencing	O
+the	O
+activity	O
+of	O
+cellular	O
+proteins	O
+involved	O
+in	O
+growth	O
+regulation	O
+.	O
+
+We	O
+have	O
+constructed	O
+,	O
+using	O
+synthetic	O
+DNA	O
+oligonucleotides	O
+,	O
+a	O
+U14	B-GENE
+snRNA	I-GENE
+gene	I-GENE
+which	O
+has	O
+been	O
+positioned	O
+behind	O
+a	O
+T7	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+promoter	I-GENE
+site	I-GENE
+and	O
+then	O
+inserted	O
+into	O
+a	O
+plasmid	O
+.	O
+
+The	O
+carcinoma	O
+was	O
+restricted	O
+within	O
+the	O
+epithelium	O
+in	O
+one	O
+,	O
+the	O
+mucosal	O
+layer	O
+in	O
+five	O
+,	O
+and	O
+the	O
+submucosal	O
+layer	O
+in	O
+two	O
+.	O
+
+In	O
+addition	O
+,	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+gamma	I-GENE
+readily	O
+heterodimerize	O
+with	O
+each	O
+other	O
+as	O
+well	O
+as	O
+with	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+alpha	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+tobacco	B-GENE
+GS	I-GENE
+-	I-GENE
+2	I-GENE
+is	O
+composed	O
+of	O
+subunits	O
+of	O
+identical	O
+size	O
+in	O
+all	O
+organs	O
+examined	O
+.	O
+
+Between	O
+acoR	B-GENE
+and	O
+acoXABC	B-GENE
+,	O
+two	O
+different	O
+types	O
+of	O
+sequences	O
+with	O
+dual	O
+rotational	O
+symmetry	O
+[	O
+CAC	O
+-	O
+(	O
+N11	O
+to	O
+N18	O
+)	O
+-	O
+GTG	O
+and	O
+TGT	O
+-	O
+(	O
+N10	O
+to	O
+N14	O
+)	O
+-	O
+ACA	O
+]	O
+were	O
+found	O
+;	O
+these	O
+sequences	O
+are	O
+similar	O
+to	O
+NtrC	B-GENE
+and	O
+NifA	B-GENE
+upstream	I-GENE
+activator	I-GENE
+sequences	I-GENE
+,	O
+respectively	O
+.	O
+
+Although	O
+the	O
+effects	O
+of	O
+the	O
+calcium	O
+supplement	O
+or	O
+calcium	O
+antagonist	O
+alone	O
+were	O
+significant	O
+,	O
+such	O
+hypotensive	O
+responses	O
+were	O
+not	O
+optimal	O
+or	O
+predictable	O
+or	O
+clearly	O
+dose	O
+-	O
+dependent	O
+.	O
+
+C	O
+.	O
+,	O
+Sun	O
+,	O
+J	O
+.	O
+,	O
+Hsu	O
+,	O
+M	O
+.	O
+-	O
+Y	O
+.	O
+,	O
+Vallejo	O
+-	O
+Ramirez	O
+,	O
+J	O
+.	O
+,	O
+Inouye	O
+,	O
+S	O
+.	O
+,	O
+and	O
+Inouye	O
+,	O
+M	O
+.	O
+
+Surprisingly	O
+,	O
+the	O
+full	O
+-	O
+deletion	O
+mutant	O
+showed	O
+a	O
+strong	O
+block	O
+in	O
+virus	O
+release	O
+,	O
+suggesting	O
+that	O
+NC	B-GENE
+is	O
+involved	O
+in	O
+virus	O
+assembly	O
+.	O
+
+Furthermore	O
+it	O
+was	O
+suggested	O
+that	O
+FK506	O
+plasma	O
+levels	O
+were	O
+concerned	O
+with	O
+the	O
+appearance	O
+of	O
+side	O
+effect	O
+.	O
+
+Thirty	O
+percent	O
+of	O
+patients	O
+were	O
+tapered	O
+off	O
+all	O
+steroids	O
+,	O
+and	O
+the	O
+average	O
+steroid	O
+dose	O
+in	O
+the	O
+group	O
+who	O
+received	O
+steroids	O
+was	O
+8	O
+.	O
+6	O
+mg	O
+of	O
+prednisone	O
+per	O
+day	O
+.	O
+
+Thus	O
+,	O
+cibenzoline	O
+is	O
+an	O
+effective	O
+antiarrhythmic	O
+agent	O
+with	O
+a	O
+favourable	O
+pharmacokinetic	O
+profile	O
+that	O
+may	O
+be	O
+considered	O
+with	O
+other	O
+class	O
+I	O
+drugs	O
+in	O
+patients	O
+requiring	O
+therapy	O
+for	O
+high	O
+risk	O
+arrhythmias	O
+.	O
+
+T	B-GENE
+antigen	I-GENE
+contains	O
+four	O
+H	O
+-	O
+2Db	O
+-	O
+restricted	O
+cytotoxic	O
+T	O
+lymphocyte	O
+(	O
+CTL	O
+)	O
+recognition	O
+epitopes	O
+that	O
+are	O
+targets	O
+for	O
+CTL	O
+clones	O
+Y	O
+-	O
+1	O
+,	O
+Y	O
+-	O
+2	O
+,	O
+Y	O
+-	O
+3	O
+,	O
+and	O
+Y	O
+-	O
+5	O
+.	O
+
+The	O
+method	O
+requires	O
+a	O
+reversed	O
+-	O
+phase	O
+column	O
+and	O
+a	O
+paired	O
+-	O
+ion	O
+technique	O
+to	O
+separate	O
+docusate	O
+sodium	O
+from	O
+other	O
+components	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+the	O
+protein	O
+product	O
+of	O
+the	O
+ref	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+stimulates	O
+the	O
+DNA	O
+binding	O
+activity	O
+of	O
+Fos	B-GENE
+-	O
+Jun	B-GENE
+heterodimers	O
+,	O
+Jun	B-GENE
+-	O
+Jun	B-GENE
+homodimers	O
+and	O
+Hela	O
+cell	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+proteins	I-GENE
+as	O
+well	O
+as	O
+that	O
+of	O
+several	O
+other	O
+transcription	O
+factors	O
+including	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+,	O
+Myb	B-GENE
+and	O
+members	O
+of	O
+the	O
+ATF	B-GENE
+/	O
+CREB	B-GENE
+family	O
+.	O
+
+The	O
+pulpal	O
+tissues	O
+of	O
+the	O
+permanent	O
+mandibular	O
+molars	O
+were	O
+amputated	O
+and	O
+then	O
+dressed	O
+with	O
+calcium	O
+hydrate	O
+.	O
+
+Northern	O
+blot	O
+analyses	O
+demonstrate	O
+that	O
+3	O
+.	O
+9	O
+-	O
+and	O
+5	O
+-	O
+kilobase	O
+mRNAs	O
+corresponding	O
+to	O
+the	O
+cDNA	O
+were	O
+present	O
+in	O
+all	O
+tissues	O
+examined	O
+,	O
+suggesting	O
+that	O
+the	O
+protein	O
+it	O
+encodes	O
+performs	O
+a	O
+housekeeping	O
+function	O
+.	O
+
+The	O
+ARG	B-GENE
+SH2	B-GENE
+domain	I-GENE
+exhibited	O
+relatively	O
+weak	O
+affinity	O
+for	O
+BCR	B-GENE
+and	O
+was	O
+determined	O
+to	O
+bind	O
+about	O
+10	O
+-	O
+fold	O
+less	O
+strongly	O
+than	O
+the	O
+ABL	B-GENE
+SH2	B-GENE
+domain	I-GENE
+.	O
+
+We	O
+analyzed	O
+an	O
+EBV	O
+B	O
+-	O
+cell	O
+clone	O
+,	O
+E29	O
+.	O
+1	O
+,	O
+derived	O
+from	O
+an	O
+11	O
+week	O
+-	O
+old	O
+embryo	O
+,	O
+and	O
+secreting	O
+both	O
+IgM	B-GENE
+kappa	I-GENE
+and	O
+IgM	B-GENE
+lambda	I-GENE
+.	O
+
+Interestingly	O
+,	O
+this	O
+activation	O
+occurred	O
+only	O
+when	O
+the	O
+regions	O
+were	O
+cloned	O
+in	O
+the	O
+same	O
+relative	O
+orientation	O
+in	O
+which	O
+they	O
+exist	O
+on	O
+wild	O
+-	O
+type	O
+pCF10	O
+.	O
+
+In	O
+rats	O
+,	O
+we	O
+examined	O
+the	O
+effect	O
+of	O
+an	O
+omentum	O
+wrapping	O
+on	O
+the	O
+vascularization	O
+of	O
+the	O
+trachea	O
+and	O
+on	O
+regeneration	O
+of	O
+the	O
+mucosal	O
+epithelium	O
+in	O
+the	O
+very	O
+early	O
+stage	O
+after	O
+free	O
+tracheal	O
+grafting	O
+.	O
+
+To	O
+study	O
+a	O
+possible	O
+functional	O
+role	O
+of	O
+this	O
+putative	O
+chicken	O
+ICS	B-GENE
+,	O
+an	O
+oligonucleotide	O
+spanning	O
+the	O
+upstream	O
+sequences	O
+of	O
+the	O
+BF	B-GENE
+-	I-GENE
+IV	I-GENE
+gene	I-GENE
+(	O
+-	O
+174	O
+/	O
+-	O
+194	O
+)	O
+was	O
+cloned	O
+singly	O
+or	O
+in	O
+multiple	O
+copies	O
+before	O
+the	O
+herpes	O
+TK	B-GENE
+promoter	I-GENE
+controlling	O
+the	O
+chloramphenicol	B-GENE
+acetyl	I-GENE
+transferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+gene	O
+(	O
+pBLCAT2	B-GENE
+)	O
+.	O
+
+In	O
+general	O
+,	O
+two	O
+separate	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatographic	O
+runs	O
+were	O
+performed	O
+,	O
+one	O
+for	O
+the	O
+gamma	O
+-	O
+aminobutyric	O
+acid	O
+determination	O
+and	O
+one	O
+for	O
+the	O
+determination	O
+of	O
+the	O
+monoamines	O
+.	O
+
+We	O
+report	O
+the	O
+successful	O
+use	O
+of	O
+electroconvulsive	O
+therapy	O
+for	O
+treatment	O
+of	O
+severe	O
+depression	O
+in	O
+a	O
+young	O
+man	O
+with	O
+adult	O
+GM2	O
+gangliosidosis	O
+.	O
+
+Through	O
+Southern	O
+blot	O
+analyses	O
+of	O
+DNA	O
+from	O
+backcross	O
+and	O
+cogenic	O
+mice	O
+,	O
+recombinant	O
+inbred	O
+strains	O
+,	O
+and	O
+somatic	O
+cell	O
+hybrids	O
+,	O
+the	O
+genetic	O
+loci	O
+that	O
+produce	O
+the	O
+cyclin	B-GENE
+B1	I-GENE
+-	I-GENE
+related	I-GENE
+sequences	I-GENE
+(	O
+designated	O
+loci	B-GENE
+Cycb1	I-GENE
+-	I-GENE
+rs1	I-GENE
+to	O
+Cycb1	B-GENE
+-	I-GENE
+rs9	I-GENE
+)	O
+were	O
+mapped	O
+on	O
+mouse	O
+chromosomes	O
+5	O
+,	O
+1	O
+,	O
+17	O
+,	O
+4	O
+,	O
+14	O
+,	O
+13	O
+,	O
+7	O
+,	O
+X	O
+,	O
+and	O
+8	O
+,	O
+respectively	O
+.	O
+
+Again	O
+residue	O
+Glu	O
+-	O
+381	O
+of	O
+beta	O
+was	O
+notably	O
+reduced	O
+and	O
+no	O
+missing	O
+residue	O
+from	O
+the	O
+epsilon	O
+peptide	O
+could	O
+be	O
+identified	O
+,	O
+but	O
+the	O
+peptide	O
+sequence	O
+limited	O
+the	O
+possible	O
+choices	O
+to	O
+Ser	O
+-	O
+106	O
+,	O
+Ser	O
+-	O
+107	O
+,	O
+or	O
+Ser	O
+-	O
+108	O
+.	O
+
+Porcelain	O
+to	O
+dentin	O
+bond	O
+strength	O
+with	O
+a	O
+dentin	O
+adhesive	O
+.	O
+
+TBPf	O
+is	O
+defined	O
+as	O
+a	O
+quotient	O
+of	O
+the	O
+difference	O
+of	O
+the	O
+first	O
+and	O
+the	O
+second	O
+measurement	O
+:	O
+TBPf	O
+=	O
+(	O
+P1	O
+-	O
+P2	O
+)	O
+/	O
+(	O
+A1	O
+-	O
+A2	O
+)	O
+.	O
+
+It	O
+was	O
+concluded	O
+that	O
+Scotchbond	O
+2	O
+and	O
+Prisma	O
+Universal	O
+Bond	O
+2	O
+are	O
+effective	O
+and	O
+are	O
+the	O
+dentine	O
+bonding	O
+agents	O
+of	O
+choice	O
+.	O
+
+The	O
+neurohypophysial	O
+vasopressin	B-GENE
+and	O
+oxytocin	B-GENE
+content	O
+was	O
+bioassayed	O
+by	O
+pressor	O
+effect	O
+following	O
+Dekanski	O
+or	O
+milk	O
+-	O
+ejection	O
+activity	O
+in	O
+vitro	O
+following	O
+van	O
+Dongen	O
+and	O
+Hays	O
+,	O
+respectively	O
+.	O
+
+Comments	O
+are	O
+given	O
+on	O
+the	O
+present	O
+status	O
+of	O
+regulations	O
+concerning	O
+water	O
+in	O
+swimming	O
+pools	O
+and	O
+baths	O
+-	O
+-	O
+1991	O
+-	O
+-	O
+(	O
+in	O
+connection	O
+with	O
+the	O
+KOK	O
+regulations	O
+-	O
+-	O
+1972	O
+-	O
+-	O
+and	O
+the	O
+Federal	O
+German	O
+standard	O
+[	O
+DIN	O
+]	O
+No	O
+.	O
+
+If	O
+no	O
+reply	O
+was	O
+received	O
+,	O
+telephone	O
+contact	O
+or	O
+home	O
+visits	O
+were	O
+made	O
+.	O
+
+The	O
+treatment	O
+group	O
+also	O
+showed	O
+in	O
+vivo	O
+T	O
+-	O
+cell	O
+activation	O
+with	O
+an	O
+initial	O
+lymphopenia	O
+followed	O
+by	O
+a	O
+rebound	O
+lymphocytosis	O
+and	O
+upregulation	O
+of	O
+the	O
+subset	O
+markers	O
+CD25	B-GENE
+(	O
+interleukin	B-GENE
+2	I-GENE
+receptor	I-GENE
+)	O
+and	O
+CD45RO	B-GENE
+(	O
+T	O
+-	O
+memory	O
+cells	O
+)	O
+.	O
+
+Urease	B-GENE
+activity	O
+,	O
+judged	O
+as	O
+the	O
+amount	O
+of	O
+ammonia	O
+production	O
+from	O
+urea	O
+,	O
+could	O
+be	O
+measured	O
+at	O
+25	O
+ng	O
+per	O
+tube	O
+(	O
+S	O
+/	O
+N	O
+=	O
+1	O
+.	O
+5	O
+)	O
+with	O
+Jack	B-GENE
+bean	I-GENE
+meal	I-GENE
+urease	I-GENE
+.	O
+
+Although	O
+a	O
+wide	O
+range	O
+of	O
+cognitive	O
+functions	O
+had	O
+been	O
+tested	O
+,	O
+all	O
+but	O
+one	O
+seizure	O
+occurred	O
+during	O
+assessment	O
+of	O
+memory	O
+performance	O
+.	O
+
+The	O
+experiments	O
+show	O
+that	O
+it	O
+is	O
+the	O
+micromilieu	O
+of	O
+the	O
+alveoli	O
+and	O
+the	O
+condition	O
+of	O
+the	O
+AM	O
+(	O
+certain	O
+physiological	O
+activation	O
+states	O
+,	O
+such	O
+as	O
+phagocytic	O
+activity	O
+)	O
+that	O
+essentially	O
+determine	O
+the	O
+degree	O
+of	O
+recovery	O
+.	O
+
+A	O
+cDNA	O
+library	O
+of	O
+tumour	O
+cells	O
+was	O
+screened	O
+with	O
+an	O
+interleukin	B-GENE
+2	I-GENE
+gene	O
+-	O
+specific	O
+probe	O
+.	O
+
+Our	O
+experiments	O
+suggest	O
+that	O
+the	O
+SCL	B-GENE
+gene	I-GENE
+can	O
+be	O
+a	O
+target	O
+for	O
+the	O
+erythroid	B-GENE
+transcription	I-GENE
+factor	I-GENE
+GATA	I-GENE
+-	I-GENE
+1	I-GENE
+and	O
+that	O
+the	O
+SCL	B-GENE
+gene	I-GENE
+product	I-GENE
+serves	O
+as	O
+a	O
+positive	O
+regulator	O
+of	O
+erythroid	O
+differentiation	O
+.	O
+
+Complexes	O
+containing	O
+wild	O
+-	O
+type	O
+and	O
+either	O
+his175	B-GENE
+or	I-GENE
+his273	I-GENE
+mutant	I-GENE
+p53	I-GENE
+proteins	I-GENE
+are	O
+completely	O
+unable	O
+to	O
+bind	O
+to	O
+the	O
+RGC	B-GENE
+DNA	I-GENE
+sequence	I-GENE
+.	O
+
+These	O
+temperature	O
+-	O
+and	O
+cold	O
+-	O
+sensitive	O
+strains	O
+were	O
+used	O
+to	O
+prepare	O
+extracts	O
+deficient	O
+in	O
+BRF1	B-GENE
+activity	O
+and	O
+were	O
+tested	O
+for	O
+transcriptional	O
+activity	O
+by	O
+RNA	B-GENE
+polymerases	I-GENE
+I	I-GENE
+,	I-GENE
+II	I-GENE
+,	I-GENE
+and	I-GENE
+III	I-GENE
+in	O
+vitro	O
+.	O
+
+These	O
+results	O
+lead	O
+us	O
+to	O
+hypothesize	O
+that	O
+a	O
+single	O
+multisubunit	B-GENE
+TFIID	I-GENE
+protein	I-GENE
+supports	O
+transcriptional	O
+stimulation	O
+by	O
+diverse	O
+activation	O
+domains	O
+and	O
+from	O
+a	O
+TATA	O
+-	O
+less	O
+promoter	O
+.	O
+
+Clone	O
+pSRc200	O
+hybrid	O
+selected	O
+an	O
+mRNA	O
+that	O
+on	O
+cell	O
+-	O
+free	O
+translation	O
+produced	O
+a	O
+38	O
+-	O
+kDa	O
+polypeptide	O
+.	O
+
+From	O
+these	O
+results	O
+,	O
+CBF	B-GENE
+-	I-GENE
+A	I-GENE
+is	O
+a	O
+novel	O
+CArG	O
+box	O
+-	O
+,	O
+ssDNA	B-GENE
+-	I-GENE
+and	I-GENE
+RNA	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+,	O
+as	O
+well	O
+as	O
+a	O
+repressive	O
+transcriptional	O
+factor	O
+.	O
+
+Cleavage	O
+by	O
+the	O
+intron	O
+-	O
+encoded	O
+enzyme	O
+(	O
+I	B-GENE
+-	I-GENE
+CreI	I-GENE
+)	O
+occurs	O
+5	O
+bp	O
+and	O
+1	O
+bp	O
+3	O
+'	O
+to	O
+the	O
+intron	O
+insertion	O
+site	O
+(	O
+in	O
+the	O
+3	O
+'	O
+-	O
+exon	O
+)	O
+in	O
+the	O
+top	O
+(	O
+/	O
+)	O
+and	O
+bottom	O
+(	O
+,	O
+)	O
+strands	O
+,	O
+respectively	O
+,	O
+resulting	O
+in	O
+4	O
+-	O
+nt	O
+single	O
+-	O
+stranded	O
+overhangs	O
+with	O
+3	O
+'	O
+-	O
+OH	O
+termini	O
+.	O
+
+Surprisingly	O
+,	O
+the	O
+Xenopus	B-GENE
+U7	I-GENE
+gene	I-GENE
+contains	O
+two	O
+adjacent	O
+octamer	O
+-	O
+binding	O
+motifs	O
+located	O
+only	O
+12	O
+and	O
+24	O
+bp	O
+upstream	O
+from	O
+the	O
+PSE	B-GENE
+,	O
+instead	O
+of	O
+the	O
+usual	O
+location	O
+around	O
+150	O
+-	O
+200	O
+bp	O
+upstream	O
+.	O
+
+The	O
+results	O
+support	O
+earlier	O
+reports	O
+that	O
+collagenase	B-GENE
+inhibitors	O
+are	O
+useful	O
+in	O
+controlling	O
+blister	O
+formation	O
+in	O
+recessive	O
+dystrophic	O
+epidermolysis	O
+bullosa	O
+.	O
+
+In	O
+humans	O
+,	O
+four	O
+AMP	B-GENE
+deaminase	I-GENE
+variants	I-GENE
+,	O
+termed	O
+M	B-GENE
+(	O
+muscle	O
+)	O
+,	O
+L	B-GENE
+(	O
+liver	O
+)	O
+,	O
+E1	B-GENE
+,	O
+and	O
+E2	B-GENE
+(	O
+erythrocyte	O
+)	O
+can	O
+be	O
+distinguished	O
+by	O
+a	O
+variety	O
+of	O
+biochemical	O
+and	O
+immunological	O
+criteria	O
+.	O
+
+Western	O
+blot	O
+analyses	O
+detect	O
+anti	B-GENE
+-	I-GENE
+E	I-GENE
+-	O
+specific	O
+immunoreactivity	O
+in	O
+affinity	O
+-	O
+purified	O
+extracts	O
+derived	O
+from	O
+the	O
+bacterial	O
+expression	O
+of	O
+a	O
+truncated	B-GENE
+AMPD3	I-GENE
+cDNA	I-GENE
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+endogenous	O
+N	O
+-	O
+methylation	O
+of	O
+salsolinol	O
+into	O
+N	O
+-	O
+methylsalsolinol	O
+occurs	O
+in	O
+the	O
+brain	O
+in	O
+vivo	O
+.	O
+
+DR1	B-GENE
+molecules	I-GENE
+purified	O
+from	O
+human	O
+lymphoblastoid	O
+cell	O
+lines	O
+could	O
+specifically	O
+bind	O
+to	O
+these	O
+peptide	O
+sequences	O
+expressed	O
+on	O
+the	O
+phage	O
+surface	O
+.	O
+
+This	O
+article	O
+describes	O
+the	O
+collaborative	O
+care	O
+of	O
+the	O
+woman	O
+participating	O
+in	O
+maternal	O
+blood	O
+donation	O
+for	O
+intrauterine	O
+transfusion	O
+.	O
+
+Chronic	O
+hepatitis	O
+B	O
+in	O
+adopted	O
+Romanian	O
+children	O
+.	O
+
+Behind	O
+the	O
+ATPase	B-GENE
+cluster	I-GENE
+,	O
+two	O
+open	O
+reading	O
+frames	O
+were	O
+detected	O
+that	O
+are	O
+not	O
+homologous	O
+to	O
+any	O
+known	O
+chloroplast	O
+gene	O
+.	O
+
+Therefore	O
+,	O
+recombinant	O
+human	O
+Ads	O
+that	O
+express	O
+noninfectious	O
+HIV	O
+or	O
+other	O
+microbial	O
+proteins	O
+are	O
+attractive	O
+vaccine	O
+candidates	O
+.	O
+
+Alignment	O
+of	O
+the	O
+selected	O
+sequences	O
+allowed	O
+us	O
+to	O
+predict	O
+a	O
+consensus	O
+sequence	O
+for	O
+binding	O
+of	O
+the	O
+individual	O
+homodimeric	O
+Rel	B-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+,	O
+and	O
+DNA	O
+-	O
+protein	O
+binding	O
+analysis	O
+of	O
+the	O
+selected	O
+DNA	O
+sequences	O
+revealed	O
+sequence	O
+specificity	O
+of	O
+the	O
+proteins	O
+.	O
+
+Using	O
+either	O
+a	O
+p50	B-GENE
+-	O
+or	O
+p65	B-GENE
+-	I-GENE
+selected	I-GENE
+kappa	I-GENE
+B	I-GENE
+motif	I-GENE
+,	O
+which	O
+displayed	O
+differential	O
+binding	O
+with	O
+respect	O
+to	O
+the	O
+other	O
+protein	O
+,	O
+little	O
+to	O
+no	O
+binding	O
+was	O
+observed	O
+with	O
+the	O
+heterodimeric	B-GENE
+NF	I-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+complex	I-GENE
+.	O
+
+However	O
+,	O
+a	O
+cosmid	O
+clone	O
+containing	O
+the	O
+entire	O
+mouse	B-GENE
+alpha	I-GENE
+1	I-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+gene	I-GENE
+,	O
+including	O
+3	O
+.	O
+7	O
+kb	O
+of	O
+5	O
+'	O
+-	O
+and	O
+4	O
+kb	O
+of	O
+3	O
+'	O
+-	O
+flanking	O
+DNA	O
+,	O
+was	O
+expressed	O
+at	O
+reduced	O
+levels	O
+in	O
+fibroblasts	O
+overexpressing	O
+oncogenic	B-GENE
+ras	I-GENE
+.	O
+
+To	O
+define	O
+transcriptional	O
+control	O
+elements	O
+responsible	O
+for	O
+muscle	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+human	B-GENE
+myoglobin	I-GENE
+gene	I-GENE
+,	O
+we	O
+performed	O
+mutational	O
+analysis	O
+of	O
+upstream	O
+sequences	O
+(	O
+nucleotide	O
+positions	O
+-	O
+373	O
+to	O
++	O
+7	O
+relative	O
+to	O
+the	O
+transcriptional	O
+start	O
+site	O
+)	O
+linked	O
+to	O
+a	O
+firefly	B-GENE
+luciferase	I-GENE
+gene	I-GENE
+.	O
+
+Sequencing	O
+analysis	O
+has	O
+shown	O
+that	O
+each	O
+rap1t	B-GENE
+allele	I-GENE
+contains	O
+a	O
+nonsense	O
+mutation	O
+within	O
+a	O
+discrete	O
+region	O
+between	O
+amino	O
+acids	O
+663	O
+and	O
+684	O
+.	O
+
+By	O
+screening	O
+a	O
+Y1	O
+cell	O
+cDNA	O
+library	O
+with	O
+the	O
+DNA	O
+-	O
+binding	O
+region	O
+of	O
+the	O
+H	B-GENE
+-	I-GENE
+2RIIBP	I-GENE
+nuclear	I-GENE
+hormone	I-GENE
+receptor	I-GENE
+cDNA	I-GENE
+,	O
+we	O
+isolated	O
+a	O
+cDNA	O
+that	O
+is	O
+selectively	O
+expressed	O
+in	O
+steroidogenic	O
+cells	O
+.	O
+
+Autopsy	O
+demonstrated	O
+good	O
+survival	O
+of	O
+the	O
+transplanted	O
+cells	O
+with	O
+good	O
+integration	O
+with	O
+the	O
+brain	O
+of	O
+the	O
+recipient	O
+and	O
+traces	O
+of	O
+positive	O
+immunocytochemical	O
+reaction	O
+for	O
+tyrosine	B-GENE
+hydroxylase	I-GENE
+.	O
+
+The	O
+technique	O
+of	O
+the	O
+TEE	O
+visualization	O
+of	O
+the	O
+proximal	O
+coronary	O
+arteries	O
+is	O
+described	O
+.	O
+
+The	O
+sequence	O
+of	O
+this	O
+region	O
+shows	O
+high	O
+G	O
++	O
+C	O
+content	O
+(	O
+62	O
+%	O
+)	O
+,	O
+which	O
+is	O
+particularly	O
+emphasized	O
+in	O
+the	O
+200	O
+bp	O
+upstream	O
+from	O
+the	O
+mRNA	O
+start	O
+(	O
+80	O
+%	O
+G	O
++	O
+C	O
+)	O
+.	O
+
+PaO2	O
+threshold	O
+was	O
+determined	O
+through	O
+an	O
+indwelling	O
+O2	O
+sensor	O
+catheter	O
+.	O
+
+By	O
+using	O
+lambda	O
+gt11	O
+expression	O
+cloning	O
+with	O
+oligonucleotides	O
+corresponding	O
+to	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+1	O
+TATA	O
+element	O
+,	O
+we	O
+report	O
+the	O
+identification	O
+of	O
+a	O
+cellular	O
+protein	O
+with	O
+a	O
+calculated	O
+molecular	O
+mass	O
+of	O
+123	O
+kDa	O
+that	O
+we	O
+designate	O
+TATA	B-GENE
+element	I-GENE
+modulatory	I-GENE
+factor	I-GENE
+(	O
+TMF	B-GENE
+)	O
+.	O
+
+Blood	O
+levels	O
+of	O
+melatonin	O
+,	O
+serotonin	O
+,	O
+cortisol	O
+,	O
+and	O
+prolactin	B-GENE
+in	O
+relation	O
+to	O
+the	O
+circadian	O
+rhythm	O
+of	O
+platelet	O
+serotonin	O
+uptake	O
+.	O
+
+We	O
+couldn	O
+'	O
+t	O
+detect	O
+any	O
+effect	O
+of	O
+n	O
+-	O
+3	O
+FA	O
+supplementation	O
+on	O
+total	O
+cholesterol	O
+,	O
+HDL	B-GENE
+cholesterol	I-GENE
+,	O
+LDL	B-GENE
+cholesterol	I-GENE
+,	O
+apo	B-GENE
+A1	I-GENE
+,	O
+Lp	B-GENE
+(	I-GENE
+a	I-GENE
+)	I-GENE
+,	O
+HbA1C	B-GENE
+,	O
+glucose	O
+,	O
+fibrinogen	B-GENE
+,	O
+factor	B-GENE
+VIII	I-GENE
+,	O
+antithrombin	B-GENE
+III	I-GENE
+,	O
+plasminogen	B-GENE
+activator	I-GENE
+inhibitor	I-GENE
+,	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+and	O
+von	B-GENE
+Willebrand	I-GENE
+factor	I-GENE
+concentration	O
+,	O
+on	O
+bleeding	O
+time	O
+or	O
+on	O
+systolic	O
+or	O
+diastolic	O
+blood	O
+pressure	O
+.	O
+
+In	O
+8	O
+healthy	O
+volunteers	O
+there	O
+were	O
+no	O
+significant	O
+differences	O
+in	O
+AUC	O
+,	O
+peak	O
+plasma	O
+concentrations	O
+or	O
+time	O
+to	O
+peak	O
+concentration	O
+when	O
+OXC	O
+was	O
+administered	O
+either	O
+with	O
+or	O
+without	O
+ERY	O
+.	O
+
+Using	O
+5	O
+ng	O
+/	O
+mL	O
+as	O
+the	O
+cutoff	O
+,	O
+the	O
+sensitivity	O
+of	O
+CEA	B-GENE
+was	O
+68	O
+%	O
+.	O
+
+Rolandic	O
+spikes	O
+and	O
+cognitive	O
+function	O
+.	O
+
+The	O
+effect	O
+of	O
+sodium	O
+18	O
+beta	O
+-	O
+glycyrrhetate	O
+(	O
+SGA	O
+)	O
+on	O
+experimental	O
+arrhythmia	O
+was	O
+investigated	O
+.	O
+
+Thus	O
+,	O
+chronic	O
+hematocrit	O
+decrease	O
+induced	O
+by	O
+H	O
+or	O
+P	O
+resulted	O
+in	O
+a	O
+significant	O
+fall	O
+in	O
+blood	O
+pressure	O
+compared	O
+to	O
+control	O
+(	O
+201	O
++	O
+/	O
+-	O
+3	O
+v	O
+175	O
++	O
+/	O
+-	O
+4	O
+,	O
+167	O
++	O
+/	O
+-	O
+4	O
+mm	O
+Hg	O
+,	O
+respectively	O
+;	O
+P	O
+<	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+effects	O
+of	O
+diltiazem	O
+were	O
+stereoselective	O
+,	O
+thus	O
+the	O
+potentiation	O
+induced	O
+by	O
+d	O
+-	O
+cis	O
+diltiazem	O
+was	O
+significantly	O
+greater	O
+in	O
+all	O
+cases	O
+than	O
+that	O
+induced	O
+by	O
+l	O
+-	O
+cis	O
+diltiazem	O
+,	O
+which	O
+suggests	O
+that	O
+calcium	O
+channel	O
+blockade	O
+plays	O
+a	O
+role	O
+in	O
+these	O
+interactions	O
+.	O
+
+Substitution	O
+of	O
+either	O
+Val33	O
+(	O
+by	O
+Gly	O
+)	O
+or	O
+Gly28	O
+(	O
+by	O
+Ser	O
+)	O
+,	O
+two	O
+of	O
+the	O
+most	O
+conserved	O
+residues	O
+in	O
+all	O
+protein	O
+kinases	O
+,	O
+resulted	O
+in	O
+enzyme	O
+with	O
+marginally	O
+detectable	O
+activity	O
+.	O
+
+Significance	O
+of	O
+the	O
+biopsy	O
+site	O
+of	O
+the	O
+latissimus	O
+dorsi	O
+muscle	O
+for	O
+fiber	O
+typing	O
+.	O
+
+The	O
+TIMP	B-GENE
+(	O
+-	O
+59	O
+/	O
+-	O
+53	O
+)	O
+AP1	B-GENE
+site	O
+is	O
+a	O
+promiscuous	O
+motif	O
+that	O
+binds	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+/	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+AP1	B-GENE
+translated	O
+in	O
+vitro	O
+and	O
+is	O
+an	O
+effective	O
+competitor	O
+for	O
+binding	O
+of	O
+nuclear	B-GENE
+AP1	I-GENE
+factors	I-GENE
+to	O
+the	O
+consensus	O
+TRE	O
+,	O
+but	O
+in	O
+addition	O
+it	O
+binds	O
+factors	O
+that	O
+do	O
+not	O
+associate	O
+with	O
+the	O
+consensus	O
+TRE	O
+.	O
+
+Involvement	O
+of	O
+AP1	B-GENE
+and	O
+PEA3	B-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+the	O
+regulation	O
+of	O
+murine	B-GENE
+tissue	I-GENE
+inhibitor	I-GENE
+of	I-GENE
+metalloproteinases	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+TIMP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+transcription	O
+.	O
+
+Of	O
+the	O
+serum	B-GENE
+neutralizing	I-GENE
+(	I-GENE
+SN	I-GENE
+)	I-GENE
+antibody	I-GENE
+negative	O
+calves	O
+89	O
+.	O
+7	O
+%	O
+(	O
+26	O
+/	O
+29	O
+)	O
+and	O
+92	O
+.	O
+8	O
+%	O
+(	O
+90	O
+/	O
+97	O
+)	O
+developed	O
+SN	B-GENE
+antibody	I-GENE
+1	O
+month	O
+after	O
+intranasal	O
+and	O
+intramuscular	O
+vaccination	O
+,	O
+respectively	O
+.	O
+
+Fractionation	O
+of	O
+crude	O
+nuclear	O
+extracts	O
+by	O
+heparin	O
+-	O
+agarose	O
+chromatography	O
+indicates	O
+that	O
+PCAT	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+more	O
+prevalent	O
+in	O
+extracts	O
+prepared	O
+from	O
+salt	O
+-	O
+stressed	O
+leaf	O
+tissue	O
+.	O
+
+A	O
+controlled	O
+trial	O
+of	O
+recombinant	B-GENE
+human	I-GENE
+granulocyte	I-GENE
+-	I-GENE
+macrophage	I-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+after	O
+total	O
+body	O
+irradiation	O
+,	O
+high	O
+-	O
+dose	O
+chemotherapy	O
+,	O
+and	O
+autologous	O
+bone	O
+marrow	O
+transplantation	O
+for	O
+acute	O
+lymphoblastic	O
+leukemia	O
+or	O
+malignant	O
+lymphoma	O
+.	O
+
+These	O
+data	O
+demonstrate	O
+that	O
+DMVA	O
+does	O
+not	O
+cause	O
+more	O
+myocardial	O
+trauma	O
+than	O
+CPB	O
+when	O
+used	O
+to	O
+provide	O
+resuscitative	O
+circulatory	O
+support	O
+.	O
+
+The	O
+IgG	B-GENE
+subclass	O
+profile	O
+of	O
+untreated	O
+coeliac	O
+disease	O
+was	O
+found	O
+to	O
+be	O
+the	O
+same	O
+as	O
+in	O
+healthy	O
+controls	O
+(	O
+IgG1	B-GENE
+approximately	O
+IgG2	B-GENE
+>	O
+IgG3	B-GENE
+>	O
+IgG4	B-GENE
+)	O
+,	O
+with	O
+only	O
+the	O
+magnitude	O
+of	O
+the	O
+individual	O
+subclass	O
+responses	O
+being	O
+increased	O
+in	O
+coeliac	O
+patients	O
+.	O
+
+Examination	O
+of	O
+ANCA	B-GENE
+is	O
+not	O
+only	O
+a	O
+significant	O
+contribution	O
+towards	O
+a	O
+more	O
+accurate	O
+diagnosis	O
+of	O
+renal	O
+vasculitis	O
+,	O
+but	O
+also	O
+an	O
+indicator	O
+of	O
+the	O
+activity	O
+of	O
+the	O
+disease	O
+and	O
+thus	O
+of	O
+the	O
+effectiveness	O
+of	O
+immunosuppressive	O
+treatment	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+total	O
+pinealectomy	O
+in	O
+these	O
+already	O
+sympathectomized	O
+blinded	O
+rabbits	O
+always	O
+resulted	O
+in	O
+a	O
+substantial	O
+deceleration	O
+of	O
+the	O
+rhythms	O
+(	O
+mean	O
+delta	O
+tau	O
+=	O
++	O
+0	O
+.	O
+23	O
+h	O
+)	O
+.	O
+
+Cicatricial	O
+pemphigoid	O
+is	O
+an	O
+autoimmune	O
+systemic	O
+disease	O
+characterized	O
+by	O
+chronic	O
+conjunctival	O
+cicatrization	O
+.	O
+
+The	O
+effects	O
+of	O
+two	O
+levels	O
+of	O
+caffeine	O
+ingestion	O
+on	O
+excess	O
+postexercise	O
+oxygen	O
+consumption	O
+in	O
+untrained	O
+women	O
+.	O
+
+The	O
+distinguishing	O
+features	O
+involved	O
+eight	O
+amino	O
+acid	O
+changes	O
+,	O
+including	O
+a	O
+single	O
+lysine	O
+deletion	O
+relative	O
+to	O
+a	O
+primate	O
+consensus	O
+sequence	O
+in	O
+the	O
+first	O
+complementary	O
+-	O
+determing	O
+region	O
+of	O
+V1J1	B-GENE
+.	O
+
+4	O
+.	O
+
+The	O
+in	O
+vivo	O
+profile	O
+of	O
+ZFH	B-GENE
+-	I-GENE
+2	I-GENE
+in	O
+the	O
+larval	O
+CNS	O
+shows	O
+intriguing	O
+overlap	O
+with	O
+DDC	B-GENE
+in	O
+specific	O
+serotonin	O
+and	O
+dopamine	O
+neurons	O
+.	O
+
+Unlike	O
+the	O
+introns	O
+of	O
+other	O
+duplicated	O
+ribosomal	B-GENE
+protein	I-GENE
+genes	I-GENE
+which	O
+are	O
+highly	O
+diverged	O
+,	O
+the	O
+duplicated	O
+S13	B-GENE
+genes	I-GENE
+have	O
+two	O
+nearly	O
+identical	O
+DNA	O
+sequences	O
+of	O
+25	O
+and	O
+31	O
+bp	O
+in	O
+length	O
+within	O
+their	O
+introns	O
+.	O
+
+In	O
+a	O
+prospective	O
+,	O
+randomized	O
+clinical	O
+trial	O
+we	O
+compared	O
+the	O
+efficacy	O
+of	O
+subcutaneously	O
+(	O
+SC	O
+)	O
+administered	O
+(	O
+every	O
+8	O
+h	O
+)	O
+calcium	O
+heparin	O
+to	O
+intravenous	O
+(	O
+IV	O
+)	O
+sodium	O
+heparin	O
+in	O
+the	O
+treatment	O
+of	O
+proximal	O
+deep	O
+-	O
+vein	O
+thrombosis	O
+(	O
+DVT	O
+)	O
+.	O
+
+The	O
+highest	O
+prevalence	O
+of	O
+reported	O
+pet	O
+allergy	O
+,	O
+chronic	O
+cough	O
+,	O
+wheeze	O
+,	O
+attacks	O
+of	O
+shortness	O
+of	O
+breath	O
+with	O
+wheezing	O
+,	O
+and	O
+doctor	O
+-	O
+diagnosed	O
+asthma	O
+was	O
+found	O
+in	O
+children	O
+who	O
+had	O
+pets	O
+in	O
+the	O
+past	O
+but	O
+not	O
+anymore	O
+.	O
+
+Therefore	O
+,	O
+it	O
+would	O
+be	O
+advantageous	O
+to	O
+identify	O
+such	O
+persons	O
+and	O
+treat	O
+them	O
+preferentially	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+these	O
+unique	O
+properties	O
+,	O
+the	O
+newly	O
+characterized	O
+hemagglutinin	B-GENE
+has	O
+been	O
+termed	O
+Limulus	B-GENE
+18K	I-GENE
+agglutination	I-GENE
+-	I-GENE
+aggregation	I-GENE
+factor	I-GENE
+(	O
+18K	B-GENE
+-	I-GENE
+LAF	I-GENE
+)	O
+.	O
+
+The	O
+shift	O
+to	O
+the	O
+nonpermissive	O
+temperature	O
+is	O
+accompanied	O
+by	O
+the	O
+loss	O
+of	O
+guanyl	O
+nucleotide	O
+-	O
+dependent	O
+activity	O
+of	O
+adenylylcyclase	B-GENE
+in	O
+vitro	O
+.	O
+
+Clin	O
+.	O
+
+The	O
+data	O
+indicate	O
+that	O
+the	O
+minimal	O
+catalytic	O
+domain	O
+of	O
+Nmt1p	B-GENE
+is	O
+located	O
+between	O
+Ile59	O
+-	O
+-	O
+>	O
+Phe96	O
+and	O
+Gly451	O
+-	O
+-	O
+>	O
+Leu455	O
+.	O
+
+It	O
+corresponds	O
+to	O
+the	O
+complete	O
+mitochondrial	O
+presequence	O
+and	O
+the	O
+lipoyl	O
+-	O
+bearing	O
+domain	O
+that	O
+are	O
+encoded	O
+by	O
+exons	O
+I	O
+through	O
+IV	O
+of	O
+the	O
+functional	O
+E2	B-GENE
+gene	I-GENE
+.	O
+
+Human	O
+neutrophil	O
+response	O
+to	O
+short	O
+-	O
+term	O
+exposure	O
+to	O
+F	O
+-	O
+75	O
+cobalt	O
+-	O
+based	O
+alloy	O
+.	O
+
+Disruption	O
+of	O
+microtubules	O
+did	O
+not	O
+affect	O
+the	O
+fidelity	O
+or	O
+kinetics	O
+of	O
+vacuolar	O
+protein	O
+sorting	O
+,	O
+indicating	O
+that	O
+Vps1p	B-GENE
+function	O
+is	O
+not	O
+dependent	O
+on	O
+microtubules	O
+.	O
+
+A	O
+mutant	O
+form	O
+of	O
+Vps1p	B-GENE
+lacking	O
+the	O
+entire	O
+GTP	O
+-	O
+binding	O
+domain	O
+interfered	O
+with	O
+vacuolar	O
+protein	O
+sorting	O
+in	O
+wild	O
+-	O
+type	O
+cells	O
+.	O
+
+According	O
+to	O
+out	O
+field	O
+research	O
+,	O
+the	O
+tick	O
+fauna	O
+was	O
+very	O
+rich	O
+throughout	O
+that	O
+area	O
+,	O
+and	O
+it	O
+was	O
+permissible	O
+enough	O
+to	O
+determine	O
+ticks	O
+as	O
+the	O
+vectors	O
+,	O
+based	O
+on	O
+arising	O
+of	O
+anti	B-GENE
+-	I-GENE
+SF	I-GENE
+group	I-GENE
+rickettsiae	I-GENE
+(	O
+SFGR	B-GENE
+)	O
+antibody	O
+in	O
+mice	O
+inoculated	O
+with	O
+some	O
+tick	O
+emulsions	O
+,	O
+findings	O
+of	O
+rickettsiae	O
+reactive	O
+to	O
+patient	O
+sera	O
+or	O
+a	O
+species	O
+-	O
+specific	O
+monoclonal	O
+antibody	O
+to	O
+JSFR	B-GENE
+in	O
+the	O
+hemolymph	O
+cells	O
+of	O
+some	O
+ticks	O
+,	O
+and	O
+electron	O
+microscopical	O
+observations	O
+of	O
+SFGR	B-GENE
+in	O
+various	O
+internal	O
+organs	O
+including	O
+the	O
+salivary	O
+gland	O
+of	O
+ticks	O
+.	O
+
+Nucleotide	O
+sequence	O
+and	O
+transcriptional	O
+analysis	O
+of	O
+the	O
+polyhedrin	B-GENE
+gene	I-GENE
+of	O
+Spodoptera	O
+exigua	O
+nuclear	O
+polyhedrosis	O
+virus	O
+.	O
+
+Validation	O
+of	O
+automated	O
+systems	O
+-	O
+-	O
+system	O
+definition	O
+.	O
+
+As	O
+a	O
+consequence	O
+of	O
+dark	O
+rearing	O
+,	O
+the	O
+numerical	O
+density	O
+of	O
+cortical	O
+neurons	O
+in	O
+area	O
+17	O
+amounted	O
+to	O
+about	O
+double	O
+of	O
+the	O
+value	O
+observed	O
+in	O
+normally	O
+reared	O
+kittens	O
+and	O
+was	O
+also	O
+significantly	O
+higher	O
+in	O
+area	O
+18	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+decreased	O
+class	O
+I	O
+enhancer	O
+activity	O
+in	O
+Ad12	O
+-	O
+transformed	O
+cells	O
+may	O
+,	O
+at	O
+least	O
+in	O
+part	O
+,	O
+be	O
+due	O
+to	O
+the	O
+higher	O
+levels	O
+of	O
+an	O
+enhancer	O
+-	O
+specific	O
+factor	O
+,	O
+possibly	O
+acting	O
+as	O
+a	O
+repressor	O
+.	O
+
+A	O
+second	O
+domain	O
+,	O
+located	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+437	O
+amino	O
+acids	O
+of	O
+IE1	B-GENE
+,	O
+is	O
+required	O
+for	O
+inhibitory	O
+and	O
+DNA	O
+-	O
+binding	O
+activities	O
+.	O
+
+In	O
+order	O
+to	O
+investigate	O
+the	O
+blood	O
+compatibility	O
+of	O
+autogenous	O
+vein	O
+graft	O
+(	O
+AVG	O
+)	O
+,	O
+changes	O
+in	O
+prostacyclin	O
+(	O
+PGI2	O
+)	O
+production	O
+following	O
+harvesting	O
+and	O
+arterial	O
+implantation	O
+were	O
+studied	O
+experimentally	O
+.	O
+
+Subcutaneous	O
+administration	O
+of	O
+the	O
+somatostatin	B-GENE
+analogue	O
+,	O
+octreotide	O
+,	O
+100	O
+micrograms	O
+thrice	O
+daily	O
+,	O
+resulted	O
+in	O
+a	O
+sustained	O
+improvement	O
+in	O
+diarrhoea	O
+and	O
+disappearance	O
+of	O
+faecal	O
+incontinence	O
+without	O
+reducing	O
+calcitonin	B-GENE
+levels	O
+.	O
+
+205	O
+,	O
+285	O
+-	O
+290	O
+]	O
+and	O
+was	O
+subsequently	O
+cloned	O
+and	O
+sequenced	O
+[	O
+J	O
+.	O
+
+Nonreplicating	O
+vaccinia	O
+vector	O
+efficiently	O
+expresses	O
+recombinant	O
+genes	O
+.	O
+
+Interferon	B-GENE
+type	I-GENE
+I	I-GENE
+in	O
+protective	O
+body	O
+reactions	O
+in	O
+an	O
+experimental	O
+Klebsiella	O
+infection	O
+
+No	O
+other	O
+changes	O
+in	O
+hematopoietic	O
+differentiation	O
+status	O
+were	O
+observed	O
+in	O
+association	O
+with	O
+Id	B-GENE
+-	I-GENE
+SCL	I-GENE
+expression	O
+.	O
+
+For	O
+pressure	O
+greater	O
+than	O
+121	O
+atm	O
+abs	O
+,	O
+an	O
+increased	O
+excitability	O
+of	O
+the	O
+tadpoles	O
+made	O
+it	O
+difficult	O
+to	O
+distinguish	O
+the	O
+righting	O
+reflex	O
+from	O
+involuntary	O
+movements	O
+.	O
+
+One	O
+air	O
+embolism	O
+occurred	O
+;	O
+this	O
+was	O
+the	O
+only	O
+filter	O
+-	O
+or	O
+retrieval	O
+-	O
+related	O
+complication	O
+.	O
+
+The	O
+5	O
+'	O
+region	O
+of	O
+ADH5	B-GENE
+contains	O
+consensus	O
+binding	O
+sites	O
+for	O
+the	O
+transcriptional	O
+regulatory	O
+proteins	O
+,	O
+Sp1	B-GENE
+,	O
+AP2	B-GENE
+,	O
+LF	B-GENE
+-	I-GENE
+A1	I-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+A2	I-GENE
+,	O
+and	O
+NF	B-GENE
+-	I-GENE
+E1	I-GENE
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+RNK	B-GENE
+-	I-GENE
+Met	I-GENE
+-	I-GENE
+1	I-GENE
+is	O
+a	O
+serine	B-GENE
+protease	I-GENE
+with	O
+unique	O
+activity	O
+that	O
+is	O
+expressed	O
+in	O
+the	O
+granules	O
+of	O
+large	O
+granular	O
+lymphocytes	O
+.	O
+
+Purification	O
+and	O
+cloning	O
+of	O
+a	O
+novel	O
+serine	B-GENE
+protease	I-GENE
+,	O
+RNK	B-GENE
+-	I-GENE
+Met	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+from	O
+the	O
+granules	O
+of	O
+a	O
+rat	O
+natural	O
+killer	O
+cell	O
+leukemia	O
+.	O
+
+We	O
+describe	O
+here	O
+17	O
+dominant	B-GENE
+GCN2	I-GENE
+mutations	I-GENE
+that	O
+lead	O
+to	O
+derepression	O
+of	O
+GCN4	B-GENE
+expression	O
+in	O
+the	O
+absence	O
+of	O
+amino	O
+acid	O
+starvation	O
+.	O
+
+Administration	O
+of	O
+growth	B-GENE
+hormone	I-GENE
+leads	O
+to	O
+faster	O
+growth	O
+,	O
+but	O
+also	O
+faster	O
+bone	O
+maturation	O
+.	O
+
+Comparisons	O
+with	O
+the	O
+available	O
+amino	O
+acid	O
+residue	O
+(	O
+aa	O
+)	O
+sequence	O
+information	O
+from	O
+the	O
+complete	O
+CPMV	B-GENE
+RNA	I-GENE
+1	I-GENE
+sequence	I-GENE
+and	O
+the	O
+partial	O
+sequence	O
+of	O
+red	B-GENE
+clover	I-GENE
+mottle	I-GENE
+virus	I-GENE
+RNA	I-GENE
+1	I-GENE
+suggest	O
+that	O
+CPSMV	B-GENE
+RNA	I-GENE
+1	I-GENE
+specifies	O
+the	O
+expected	O
+set	O
+of	O
+five	O
+mature	O
+proteins	O
+:	O
+32K	B-GENE
+proteinase	I-GENE
+cofactor	I-GENE
+,	O
+58K	B-GENE
+presumed	I-GENE
+helicase	I-GENE
+,	O
+VPg	B-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+linked	I-GENE
+protein	I-GENE
+of	O
+the	O
+genomic	O
+RNAs	O
+,	O
+24K	B-GENE
+proteinase	I-GENE
+,	O
+and	O
+87K	B-GENE
+presumed	I-GENE
+polymerase	I-GENE
+,	O
+separated	O
+by	O
+four	O
+cleavage	O
+sites	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+utility	O
+of	O
+beta	B-GENE
+2	I-GENE
+transferrin	I-GENE
+assay	O
+in	O
+the	O
+diagnosis	O
+of	O
+cerebrospinal	O
+fluid	O
+otorrhea	O
+is	O
+presented	O
+.	O
+
+The	O
+addition	O
+of	O
+diatrizoate	O
+to	O
+the	O
+IPRK	O
+led	O
+to	O
+a	O
+dose	O
+-	O
+dependent	O
+biphasic	O
+change	O
+in	O
+RPF	O
+and	O
+GFR	O
+characterized	O
+by	O
+an	O
+initial	O
+transient	O
+increase	O
+followed	O
+by	O
+a	O
+marked	O
+and	O
+sustained	O
+decrease	O
+.	O
+
+To	O
+prepare	O
+for	O
+analyses	O
+with	O
+the	O
+family	O
+variables	O
+,	O
+we	O
+next	O
+present	O
+descriptive	O
+data	O
+based	O
+on	O
+separate	O
+principal	O
+components	O
+analysis	O
+(	O
+PCA	O
+)	O
+and	O
+multidimensional	O
+scaling	O
+analysis	O
+(	O
+MDS	O
+)	O
+of	O
+14	O
+self	O
+-	O
+reported	O
+health	O
+scores	O
+for	O
+husbands	O
+and	O
+for	O
+wives	O
+.	O
+
+The	O
+structural	O
+genes	O
+encoding	O
+glyceraldehyde	B-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+phosphate	I-GENE
+dehydrogenase	I-GENE
+(	O
+GAPDH	B-GENE
+)	O
+,	O
+3	B-GENE
+-	I-GENE
+phosphoglycerate	I-GENE
+kinase	I-GENE
+(	O
+PGK	B-GENE
+)	O
+and	O
+the	O
+N	O
+-	O
+terminal	O
+part	O
+of	O
+triosephosphate	B-GENE
+isomerase	I-GENE
+(	O
+TIM	B-GENE
+)	O
+from	O
+mesophilic	O
+Bacillus	O
+megaterium	O
+DSM319	O
+have	O
+been	O
+cloned	O
+as	O
+a	O
+gene	O
+cluster	O
+(	O
+gap	B-GENE
+operon	I-GENE
+)	O
+by	O
+complementation	O
+of	O
+an	O
+Escherichia	O
+coli	O
+gap	B-GENE
+amber	I-GENE
+mutant	I-GENE
+.	O
+
+Pseudomonas	B-GENE
+aeruginosa	I-GENE
+exotoxin	I-GENE
+A	I-GENE
+:	O
+its	O
+role	O
+in	O
+retardation	O
+of	O
+wound	O
+healing	O
+:	O
+the	O
+1992	O
+Lindberg	O
+Award	O
+.	O
+
+Laboratory	O
+studies	O
+showed	O
+that	O
+the	O
+direct	O
+fluorescent	O
+-	O
+antibody	O
+kits	O
+were	O
+the	O
+least	O
+sensitive	O
+in	O
+this	O
+case	O
+and	O
+did	O
+not	O
+detect	O
+fewer	O
+than	O
+10	O
+(	O
+4	O
+)	O
+elementary	O
+bodies	O
+per	O
+ml	O
+,	O
+while	O
+most	O
+ELISA	O
+kits	O
+detected	O
+between	O
+130	O
+and	O
+600	O
+elementary	O
+bodies	O
+per	O
+ml	O
+.	O
+
+To	O
+study	O
+the	O
+significance	O
+of	O
+these	O
+domains	O
+and	O
+the	O
+overall	O
+evolutionary	O
+conservation	O
+of	O
+the	O
+gene	O
+,	O
+the	O
+homolog	O
+from	O
+Drosophila	O
+melanogaster	O
+was	O
+isolated	O
+by	O
+low	O
+stringency	O
+hybridizations	O
+using	O
+two	O
+flanking	O
+probes	O
+of	O
+the	O
+human	B-GENE
+ERCC3	I-GENE
+cDNA	I-GENE
+.	O
+
+Mono	O
+-	O
+ADP	O
+-	O
+ribosylation	O
+is	O
+a	O
+reversible	O
+modification	O
+of	O
+proteins	O
+,	O
+with	O
+NAD	O
+:	O
+arginine	B-GENE
+ADP	I-GENE
+-	I-GENE
+ribosyltransferases	I-GENE
+(	O
+EC	B-GENE
+2	I-GENE
+.	I-GENE
+4	I-GENE
+.	I-GENE
+2	I-GENE
+.	I-GENE
+31	I-GENE
+)	O
+and	O
+ADP	B-GENE
+-	I-GENE
+ribosylarginine	I-GENE
+hydrolases	I-GENE
+(	O
+EC	B-GENE
+3	I-GENE
+.	I-GENE
+2	I-GENE
+.	I-GENE
+2	I-GENE
+.	I-GENE
+19	I-GENE
+)	O
+catalyzing	O
+the	O
+opposing	O
+reactions	O
+in	O
+an	O
+ADP	O
+-	O
+ribosylation	O
+cycle	O
+.	O
+
+For	O
+this	O
+reason	O
+,	O
+the	O
+particle	O
+forming	O
+capacity	O
+of	O
+derivatives	O
+of	O
+the	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+group	I-GENE
+specific	I-GENE
+core	I-GENE
+antigen	I-GENE
+p55	I-GENE
+gag	I-GENE
+was	O
+assayed	O
+and	O
+compared	O
+dependent	O
+on	O
+various	O
+expression	O
+systems	O
+:	O
+recombinant	O
+bacteria	O
+,	O
+vaccinia	O
+-	O
+and	O
+baculoviruses	O
+were	O
+established	O
+encoding	O
+the	O
+entire	O
+core	B-GENE
+protein	I-GENE
+p55	I-GENE
+either	O
+in	O
+its	O
+authentic	O
+sequence	O
+or	O
+lacking	O
+the	O
+myristylation	O
+consensus	O
+signal	O
+.	O
+
+The	O
+tramtrack	B-GENE
+(	O
+ttk	B-GENE
+)	O
+gene	O
+of	O
+Drosophila	O
+encodes	O
+69	O
+-	O
+kDa	O
+and	O
+88	O
+-	O
+kDa	O
+proteins	O
+through	O
+alternative	O
+splicing	O
+of	O
+the	O
+primary	O
+ttk	B-GENE
+transcript	I-GENE
+.	O
+
+Removal	O
+of	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+by	O
+hemodialysis	O
+and	O
+hemofiltration	O
+:	O
+a	O
+four	O
+year	O
+follow	O
+up	O
+.	O
+
+Removal	O
+of	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+by	O
+hemodialysis	O
+and	O
+hemofiltration	O
+:	O
+a	O
+four	O
+year	O
+follow	O
+up	O
+.	O
+
+Adapromine	O
+was	O
+established	O
+to	O
+evoke	O
+a	O
+decrease	O
+of	O
+the	O
+amplitude	O
+of	O
+the	O
+dominant	O
+peak	O
+and	O
+dominant	O
+theta	O
+-	O
+activity	O
+in	O
+power	O
+spectra	O
+of	O
+the	O
+EEG	O
+in	O
+the	O
+cortex	O
+and	O
+hippocamp	O
+,	O
+with	O
+an	O
+increase	O
+of	O
+rapid	O
+wave	O
+activity	O
+in	O
+the	O
+beta	O
+2	O
+range	O
+in	O
+the	O
+right	O
+cortex	O
+and	O
+hippocamp	O
+.	O
+
+These	O
+sequences	O
+were	O
+then	O
+used	O
+to	O
+clone	O
+the	O
+full	O
+-	O
+length	O
+genes	O
+from	O
+a	O
+yeast	O
+genomic	O
+library	O
+.	O
+
+GAL4	B-GENE
+-	O
+VP16	B-GENE
+-	O
+mediated	O
+antirepression	O
+required	O
+an	O
+auxiliary	O
+factor	O
+,	O
+denoted	O
+as	O
+a	O
+co	O
+-	O
+antirepressor	O
+,	O
+which	O
+was	O
+partially	O
+purified	O
+from	O
+Drosophila	O
+embryos	O
+.	O
+
+After	O
+28	O
+days	O
+of	O
+haloperidol	O
+treatment	O
+,	O
+similar	O
+changes	O
+were	O
+observed	O
+for	O
+delta	O
+,	O
+together	O
+with	O
+an	O
+increase	O
+of	O
+alpha	O
+1	O
+,	O
+and	O
+a	O
+decrease	O
+of	O
+fast	O
+beta	O
+.	O
+
+Four	O
+ruminally	O
+and	O
+duodenally	O
+cannulated	O
+Hampshire	O
+wethers	O
+were	O
+used	O
+in	O
+a	O
+4	O
+x	O
+4	O
+Latin	O
+square	O
+experiment	O
+to	O
+determine	O
+whether	O
+linoleoyl	O
+methionine	O
+and	O
+calcium	O
+linoleate	O
+would	O
+increase	O
+duodenal	O
+flow	O
+of	O
+unsaturated	O
+fatty	O
+acids	O
+(	O
+C18	O
+:	O
+2	O
++	O
+cis	O
+C18	O
+:	O
+1	O
+)	O
+.	O
+
+Truncated	B-GENE
+ICSBP	I-GENE
+lacking	O
+the	O
+first	O
+33	O
+amino	O
+-	O
+terminal	O
+amino	O
+acids	O
+fails	O
+to	O
+bind	O
+to	O
+the	O
+ICS	B-GENE
+,	O
+indicating	O
+that	O
+at	O
+least	O
+part	O
+of	O
+the	O
+DNA	O
+binding	O
+domain	O
+is	O
+located	O
+within	O
+the	O
+well	O
+conserved	O
+amino	O
+terminus	O
+.	O
+
+Therefore	O
+,	O
+ICSBP	B-GENE
+may	O
+be	O
+involved	O
+in	O
+maintaining	O
+submaximal	O
+transcriptional	O
+activity	O
+of	O
+IFN	B-GENE
+-	O
+inducible	O
+genes	O
+in	O
+hematopoietic	O
+cells	O
+.	O
+
+A	O
+case	O
+of	O
+chronic	O
+hepatitis	O
+C	O
+with	O
+primary	O
+hypothyroidism	O
+manifested	O
+during	O
+interferon	B-GENE
+treatment	O
+
+Dynamic	O
+decision	O
+making	O
+:	O
+human	O
+control	O
+of	O
+complex	O
+systems	O
+.	O
+
+A	O
+coiled	B-GENE
+-	I-GENE
+coil	I-GENE
+related	I-GENE
+protein	I-GENE
+specific	O
+for	O
+synapsed	O
+regions	O
+of	O
+meiotic	O
+prophase	O
+chromosomes	O
+.	O
+
+Abstracts	O
+.	O
+
+These	O
+results	O
+indicate	O
+a	O
+possible	O
+involvement	O
+of	O
+endogenous	O
+opioid	O
+peptides	O
+in	O
+the	O
+cardiac	O
+effects	O
+due	O
+to	O
+myocardial	O
+ischaemia	O
+and	O
+reperfusion	O
+,	O
+mediated	O
+by	O
+opiate	B-GENE
+receptors	I-GENE
+through	O
+opiate	O
+antagonism	O
+.	O
+
+Since	O
+CENP	B-GENE
+-	I-GENE
+B	I-GENE
+gene	I-GENE
+is	O
+conserved	O
+in	O
+mammalian	O
+species	O
+and	O
+CENP	B-GENE
+-	I-GENE
+B	I-GENE
+boxes	I-GENE
+are	O
+found	O
+also	O
+in	O
+mouse	O
+centromere	O
+satellite	O
+DNA	O
+(	O
+minor	O
+satellite	O
+)	O
+,	O
+this	O
+sequence	O
+-	O
+specific	O
+DNA	O
+-	O
+protein	O
+interaction	O
+may	O
+be	O
+important	O
+for	O
+some	O
+kind	O
+of	O
+common	O
+centromere	O
+function	O
+.	O
+
+Interestingly	O
+,	O
+a	O
+portion	O
+of	O
+the	O
+tail	O
+domain	O
+(	O
+aa	O
+,	O
+1	O
+,	O
+094	O
+-	O
+1	O
+,	O
+830	O
+)	O
+shares	O
+58	O
+%	O
+amino	O
+acid	O
+sequence	O
+identity	O
+with	O
+a	O
+723	O
+-	O
+aa	O
+protein	O
+from	O
+mouse	O
+brain	O
+reported	O
+to	O
+be	O
+a	O
+glutamic	B-GENE
+acid	I-GENE
+decarboxylase	I-GENE
+.	O
+
+However	O
+,	O
+in	O
+the	O
+subgroup	O
+with	O
+normal	O
+Ht	O
+(	O
+<	O
+0	O
+.	O
+45	O
+l	O
+/	O
+l	O
+;	O
+n	O
+=	O
+201	O
+)	O
+there	O
+was	O
+a	O
+significant	O
+reduction	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+of	O
+the	O
+mortality	O
+after	O
+3	O
+months	O
+(	O
+27	O
+%	O
+and	O
+16	O
+%	O
+,	O
+respectively	O
+)	O
+and	O
+an	O
+increase	O
+of	O
+independence	O
+at	O
+home	O
+(	O
+35	O
+%	O
+and	O
+48	O
+%	O
+,	O
+respectively	O
+)	O
+due	O
+to	O
+a	O
+reduction	O
+of	O
+the	O
+viscosity	O
+by	O
+means	O
+of	O
+haemodilution	O
+with	O
+albumin	B-GENE
+(	O
+a	O
+specific	O
+viscosity	O
+effect	O
+in	O
+the	O
+normovolaemic	O
+group	O
+)	O
+.	O
+
+Distribution	O
+and	O
+changing	O
+morphological	O
+course	O
+
+The	O
+appropriate	O
+use	O
+and	O
+benefits	O
+of	O
+bile	O
+acid	O
+sequestrants	O
+,	O
+nicotinic	O
+acid	O
+,	O
+fibric	O
+acids	O
+,	O
+3	B-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+methylglutaryl	I-GENE
+coenzyme	I-GENE
+A	I-GENE
+(	I-GENE
+HMG	I-GENE
+-	I-GENE
+CoA	I-GENE
+)	I-GENE
+reductase	I-GENE
+inhibitors	O
+,	O
+and	O
+probucol	O
+are	O
+individually	O
+discussed	O
+,	O
+whereas	O
+nonpharmacologic	O
+approaches	O
+used	O
+in	O
+conjunction	O
+with	O
+the	O
+drugs	O
+are	O
+recommended	O
+emphatically	O
+.	O
+
+This	O
+may	O
+result	O
+in	O
+more	O
+reabsorption	O
+and	O
+hence	O
+reduced	O
+renal	O
+clearance	O
+.	O
+
+The	O
+major	O
+pathological	O
+findings	O
+of	O
+the	O
+placenta	O
+were	O
+prematuration	O
+and	O
+hypoplasia	O
+.	O
+
+Green	O
+pepper	O
+significantly	O
+inhibited	O
+N	O
+-	O
+nitrosothiazolidine	O
+-	O
+carboxylic	O
+acid	O
+formation	O
+relative	O
+to	O
+ascorbic	O
+acid	O
+alone	O
+.	O
+
+A	O
+genomic	O
+clone	O
+,	O
+pTt21	O
+,	O
+containing	O
+DNA	O
+apparently	O
+transcribed	O
+specifically	O
+in	O
+Trypanosoma	O
+cruzi	O
+trypomastigotes	O
+,	O
+was	O
+obtained	O
+by	O
+differentially	O
+screening	O
+a	O
+genomic	O
+library	O
+with	O
+trypomastigote	O
+and	O
+epimastigote	O
+cDNA	O
+.	O
+
+Brucellosis	O
+-	O
+-	O
+1990	O
+
+Assay	O
+of	O
+urea	O
+by	O
+immobilized	O
+urease	B-GENE
+coupled	O
+to	O
+a	O
+differential	O
+pH	O
+-	O
+meter	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+the	O
+AGA	O
+group	O
+,	O
+both	O
+fetal	O
+and	O
+maternal	O
+serum	O
+prolactin	B-GENE
+concentration	O
+increased	O
+significantly	O
+with	O
+gestation	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+and	O
+P	O
+<	O
+0	O
+.	O
+01	O
+,	O
+respectively	O
+)	O
+.	O
+
+One	O
+phage	O
+clone	O
+contains	O
+a	O
+junction	O
+between	O
+alpha	O
+satellite	O
+DNA	O
+and	O
+a	O
+novel	O
+low	O
+-	O
+copy	O
+repeated	O
+sequence	O
+.	O
+
+The	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+lactoferrin	I-GENE
+gene	I-GENE
+was	O
+isolated	O
+from	O
+a	O
+human	O
+placental	O
+genomic	O
+library	O
+.	O
+
+Therefore	O
+,	O
+the	O
+molecular	O
+mechanisms	O
+of	O
+the	O
+estrogen	O
+action	O
+that	O
+govern	O
+the	O
+lactoferrin	B-GENE
+gene	I-GENE
+expression	O
+differ	O
+between	O
+mouse	O
+and	O
+human	O
+.	O
+
+The	O
+CEM	O
+receives	O
+registration	O
+updates	O
+via	O
+an	O
+HL7	O
+message	O
+and	O
+evaluates	O
+data	O
+dependencies	O
+in	O
+rules	O
+via	O
+an	O
+interface	O
+to	O
+the	O
+relational	O
+database	O
+.	O
+
+Magnetic	O
+resonance	O
+spectroscopy	O
+(	O
+MRS	O
+)	O
+and	O
+imaging	O
+(	O
+MRI	O
+)	O
+are	O
+now	O
+well	O
+established	O
+techniques	O
+for	O
+the	O
+study	O
+of	O
+cellular	O
+metabolism	O
+and	O
+gross	O
+structure	O
+of	O
+muscle	O
+.	O
+
+Simultaneously	O
+a	O
+greater	O
+NA	O
+was	O
+found	O
+with	O
+no	O
+change	O
+in	O
+plasma	O
+epinephrine	O
+response	O
+.	O
+
+We	O
+investigated	O
+the	O
+diagnostic	O
+value	O
+of	O
+a	O
+new	O
+in	O
+vitro	O
+test	O
+,	O
+Pharmacia	O
+CAP	O
+System	O
+(	O
+Pharmacia	O
+Diagnostics	O
+AB	O
+,	O
+Uppsala	O
+,	O
+Sweden	O
+)	O
+,	O
+for	O
+the	O
+quantitative	O
+measurement	O
+of	O
+allergen	B-GENE
+-	I-GENE
+specific	I-GENE
+IgE	I-GENE
+antibodies	I-GENE
+by	O
+comparison	O
+with	O
+RAST	O
+in	O
+2	O
+groups	O
+of	O
+patients	O
+,	O
+71	O
+atopic	O
+and	O
+48	O
+non	O
+-	O
+atopic	O
+.	O
+
+Patients	O
+receiving	O
+VPA	O
+showed	O
+differences	O
+in	O
+attention	O
+,	O
+visuomotor	O
+performance	O
+,	O
+verbal	O
+span	O
+and	O
+sensory	O
+discrimination	O
+tasks	O
+at	O
+T1	O
+,	O
+in	O
+visuomotor	O
+performance	O
+at	O
+T2	O
+and	O
+in	O
+spatial	O
+span	O
+at	O
+T3	O
+,	O
+whereas	O
+no	O
+differences	O
+were	O
+detected	O
+at	O
+T4	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+gene	O
+segment	O
+containing	O
+the	O
+mu	O
+m	O
+poly	O
+(	O
+A	O
+)	O
+signals	O
+,	O
+along	O
+with	O
+536	O
+bp	O
+of	O
+downstream	O
+flanking	O
+sequence	O
+,	O
+acted	O
+as	O
+a	O
+transcription	O
+terminator	O
+in	O
+both	O
+myeloma	O
+cells	O
+and	O
+L	O
+cell	O
+fibroblasts	O
+.	O
+
+Alena	O
+is	O
+a	O
+nurse	O
+in	O
+Prague	O
+-	O
+-	O
+she	O
+dreams	O
+of	O
+higher	O
+wages	O
+and	O
+a	O
+trip	O
+across	O
+the	O
+ocean	O
+
+Dopamine	O
+neurons	O
+in	O
+subjects	O
+that	O
+received	O
+6	O
+-	O
+OHDA	O
+were	O
+protected	O
+by	O
+pre	O
+-	O
+treatment	O
+with	O
+GBR	O
+-	O
+12909	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+study	O
+demonstrate	O
+that	O
+strongyloidiasis	O
+was	O
+the	O
+cause	O
+of	O
+sudden	O
+death	O
+.	O
+
+A	O
+second	O
+large	O
+group	O
+of	O
+disorders	O
+in	O
+pregnancy	O
+is	O
+caused	O
+by	O
+effects	O
+of	O
+infections	O
+of	O
+the	O
+mother	O
+without	O
+pathogens	O
+being	O
+transmitted	O
+to	O
+the	O
+embryo	O
+or	O
+the	O
+placenta	O
+.	O
+
+Four	O
+short	O
+nucleotide	O
+sequences	O
+(	O
+boxes	O
+I	O
+to	O
+IV	O
+)	O
+contribute	O
+to	O
+the	O
+light	O
+responsiveness	O
+of	O
+the	O
+parsley	B-GENE
+chalcone	I-GENE
+synthase	I-GENE
+promoter	I-GENE
+.	O
+
+The	O
+case	O
+described	O
+is	O
+that	O
+of	O
+a	O
+72	O
+-	O
+year	O
+-	O
+old	O
+man	O
+with	O
+ochronosis	O
+who	O
+suffered	O
+a	O
+hyperextension	O
+injury	O
+to	O
+his	O
+spine	O
+in	O
+a	O
+fall	O
+,	O
+resulting	O
+in	O
+a	O
+fracture	O
+through	O
+an	O
+ankylosed	O
+L2	O
+-	O
+L3	O
+disk	O
+space	O
+.	O
+
+The	O
+mean	O
+blood	O
+flow	O
+in	O
+the	O
+penile	O
+foreskin	O
+was	O
+estimated	O
+to	O
+be	O
+15	O
+ml	O
+/	O
+min	O
+/	O
+100	O
+g	O
+and	O
+it	O
+increased	O
+to	O
+150	O
+-	O
+200	O
+%	O
+after	O
+the	O
+induction	O
+of	O
+anesthesia	O
+,	O
+and	O
+then	O
+decreased	O
+to	O
+72	O
+%	O
+at	O
+the	O
+tip	O
+of	O
+the	O
+created	O
+parameatal	O
+foreskin	O
+flap	O
+.	O
+
+Exogenous	O
+LHRH	B-GENE
+is	O
+also	O
+known	O
+to	O
+facilitate	O
+mating	O
+behavior	O
+in	O
+several	O
+species	O
+.	O
+
+The	O
+first	O
+146	O
+consecutive	O
+patients	O
+treated	O
+with	O
+EVL	O
+during	O
+the	O
+period	O
+from	O
+August	O
+,	O
+1986	O
+to	O
+July	O
+,	O
+1989	O
+are	O
+reported	O
+.	O
+
+Replacing	O
+the	O
+aspartic	O
+acid	O
+with	O
+a	O
+lysine	O
+but	O
+not	O
+with	O
+an	O
+alanine	O
+or	O
+valine	O
+residue	O
+allowed	O
+formation	O
+of	O
+disulfide	O
+-	O
+linked	O
+dimers	O
+.	O
+
+During	O
+V	O
+-	O
+A	O
+bypass	O
+,	O
+hemodynamics	O
+were	O
+stable	O
+.	O
+
+Greater	O
+rupture	O
+force	O
+was	O
+required	O
+in	O
+the	O
+adult	O
+pigs	O
+than	O
+in	O
+the	O
+young	O
+pigs	O
+.	O
+
+At	O
+rest	O
+AFF	O
+was	O
+significantly	O
+higher	O
+in	O
+UT	O
+(	O
+29	O
+%	O
+)	O
+as	O
+compared	O
+to	O
+AT	O
+(	O
+25	O
+%	O
+)	O
+and	O
+UEA	O
+(	O
+25	O
+%	O
+)	O
+.	O
+
+We	O
+investigated	O
+the	O
+smoking	O
+habits	O
+of	O
+relapsers	O
+1	O
+year	O
+after	O
+quitting	O
+in	O
+a	O
+smoking	O
+cessation	O
+trial	O
+using	O
+nicotine	O
+or	O
+placebo	O
+patches	O
+.	O
+
+Exposure	O
+to	O
+hepatitis	O
+B	O
+virus	O
+in	O
+the	O
+general	O
+population	O
+of	O
+Hisayama	O
+,	O
+Japan	O
+:	O
+significance	O
+of	O
+isolated	O
+antibody	O
+to	O
+hepatitis	B-GENE
+B	I-GENE
+surface	I-GENE
+antigen	I-GENE
+in	O
+general	O
+population	O
+.	O
+
+Because	O
+of	O
+this	O
+latter	O
+phenomenon	O
+,	O
+we	O
+were	O
+able	O
+to	O
+identify	O
+a	O
+particular	O
+cysteine	O
+motif	O
+that	O
+was	O
+repeated	O
+multiple	O
+times	O
+in	O
+Dfurin2	B-GENE
+but	O
+present	O
+only	O
+twice	O
+in	O
+mammalian	B-GENE
+furin	I-GENE
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+neither	O
+phosphate	O
+buffered	O
+saline	O
+injection	O
+into	O
+the	O
+ES	O
+nor	O
+primary	O
+KLH	B-GENE
+challenges	O
+of	O
+the	O
+ES	O
+were	O
+capable	O
+of	O
+elevating	O
+the	O
+threshold	O
+level	O
+and	O
+changing	O
+the	O
+latency	O
+.	O
+
+A	O
+newly	O
+developed	O
+broad	O
+-	O
+spectrum	O
+fluoroquinolone	O
+,	O
+levofloxacin	O
+(	O
+LVFX	O
+,	O
+DR	O
+-	O
+3355	O
+)	O
+,	O
+was	O
+evaluated	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+in	O
+comparison	O
+with	O
+ciprofloxacin	O
+(	O
+CPFX	O
+)	O
+,	O
+ofloxacin	O
+(	O
+OFLX	O
+)	O
+and	O
+norfloxacin	O
+(	O
+NFLX	O
+)	O
+.	O
+
+The	O
+mean	O
+serum	O
+creatinine	O
+levels	O
+were	O
+similar	O
+at	O
+one	O
+year	O
+(	O
+SPK	O
+1	O
+.	O
+8	O
+,	O
+KTA	O
+1	O
+.	O
+9	O
+mg	O
+/	O
+d	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Model	O
+predictions	O
+were	O
+in	O
+accord	O
+with	O
+the	O
+nine	O
+-	O
+year	O
+survival	O
+experience	O
+of	O
+women	O
+in	O
+the	O
+HIP	O
+trial	O
+,	O
+and	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+women	O
+40	O
+-	O
+44	O
+years	O
+old	O
+,	O
+with	O
+HIP	O
+data	O
+on	O
+18	O
+-	O
+year	O
+survival	O
+.	O
+
+High	O
+-	O
+resolution	O
+computed	O
+tomography	O
+in	O
+the	O
+diagnosis	O
+of	O
+miliary	O
+tuberculosis	O
+.	O
+
+Previously	O
+,	O
+we	O
+showed	O
+that	O
+SNF2	B-GENE
+,	O
+SNF5	B-GENE
+,	O
+and	O
+SNF6	B-GENE
+function	O
+interdependently	O
+in	O
+transcriptional	O
+activation	O
+,	O
+possibly	O
+forming	O
+a	O
+heteromeric	O
+complex	O
+.	O
+
+We	O
+show	O
+that	O
+LexA	B-GENE
+-	O
+GAL4	B-GENE
+and	O
+LexA	B-GENE
+-	O
+Bicoid	B-GENE
+fusion	O
+proteins	O
+are	O
+both	O
+dependent	O
+on	O
+SNF2	B-GENE
+,	O
+SNF5	B-GENE
+,	O
+and	O
+SNF6	B-GENE
+for	O
+activation	O
+of	O
+target	O
+genes	O
+containing	O
+one	O
+or	O
+multiple	O
+lexA	B-GENE
+operators	I-GENE
+.	O
+
+George	O
+T	O
+.	O
+
+A	O
+lambda	O
+gt10	O
+cDNA	O
+library	O
+was	O
+constructed	O
+from	O
+poly	O
+(	O
+A	O
+)	O
++	O
+RNA	O
+of	O
+young	O
+green	O
+leaves	O
+of	O
+spinach	O
+.	O
+
+NE	B-GENE
+and	O
+PR3	B-GENE
+assist	O
+in	O
+the	O
+destruction	O
+of	O
+phagocytosed	O
+microorganisms	O
+,	O
+cleave	O
+the	O
+important	O
+connective	B-GENE
+-	I-GENE
+tissue	I-GENE
+protein	I-GENE
+elastin	I-GENE
+,	O
+and	O
+generate	O
+chemotactic	O
+activities	O
+by	O
+forming	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+proteinase	I-GENE
+inhibitor	I-GENE
+complexes	I-GENE
+and	O
+elastin	B-GENE
+peptides	I-GENE
+.	O
+
+Selected	O
+topics	O
+in	O
+pediatric	O
+ultrasonography	O
+-	O
+-	O
+1992	O
+.	O
+
+Methods	O
+included	O
+24	O
+-	O
+hour	O
+dietary	O
+recall	O
+,	O
+menu	O
+weights	O
+,	O
+and	O
+recipe	O
+analysis	O
+.	O
+
+Factors	O
+associated	O
+with	O
+afterdrop	O
+included	O
+age	O
+,	O
+end	O
+-	O
+of	O
+-	O
+surgery	O
+temperature	O
+(	O
+both	O
+positively	O
+)	O
+and	O
+body	O
+mass	O
+(	O
+negatively	O
+)	O
+.	O
+
+Both	O
+GH	B-GENE
+deficiency	O
+and	O
+impaired	O
+spinal	O
+growth	O
+may	O
+result	O
+in	O
+short	O
+stature	O
+,	O
+whereas	O
+the	O
+occurrence	O
+of	O
+early	O
+puberty	O
+in	O
+association	O
+with	O
+GH	B-GENE
+deficiency	O
+reduces	O
+the	O
+time	O
+available	O
+for	O
+GH	B-GENE
+therapy	O
+.	O
+
+By	O
+contrast	O
+,	O
+d	B-GENE
+(	I-GENE
+T2AG3T	I-GENE
+)	I-GENE
+and	O
+d	B-GENE
+(	I-GENE
+T2G4T	I-GENE
+)	I-GENE
+form	O
+only	O
+the	O
+G	O
+-	O
+quadruplex	O
+monomer	O
+structures	O
+independent	O
+of	O
+K	O
+cation	O
+concentration	O
+as	O
+reported	O
+previously	O
+[	O
+Sen	O
+,	O
+D	O
+.	O
+,	O
+&	O
+Gilbert	O
+,	O
+W	O
+.	O
+
+Differentiating	O
+among	O
+renal	O
+stones	O
+.	O
+
+IFI	B-GENE
+16	I-GENE
+mRNA	I-GENE
+was	O
+found	O
+to	O
+be	O
+constitutively	O
+expressed	O
+in	O
+lymphoid	O
+cells	O
+and	O
+in	O
+cell	O
+lines	O
+of	O
+both	O
+the	O
+T	O
+and	O
+B	O
+lineages	O
+.	O
+
+Mitochondria	O
+-	O
+lytic	O
+action	O
+of	O
+warfarin	O
+in	O
+lymphocytes	O
+.	O
+
+Exon	O
+-	O
+intron	O
+junctions	O
+in	O
+the	O
+human	O
+and	O
+rat	B-GENE
+AdoMet	I-GENE
+decarboxylase	I-GENE
+genes	I-GENE
+were	O
+in	O
+identical	O
+positions	O
+except	O
+that	O
+exons	O
+6	O
+and	O
+7	O
+of	O
+the	O
+human	O
+gene	O
+formed	O
+a	O
+single	O
+exon	O
+in	O
+the	O
+rat	O
+gene	O
+.	O
+
+Interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+-	O
+induced	O
+gene	O
+expression	O
+:	O
+evidence	O
+for	O
+a	O
+selective	O
+effect	O
+of	O
+ouabain	O
+on	O
+activation	O
+of	O
+the	O
+ISGF3	B-GENE
+transcription	I-GENE
+complex	I-GENE
+.	O
+
+Moreover	O
+,	O
+LD50	O
+in	O
+mice	O
+of	O
+RP	O
+-	O
+170	O
+(	O
+4	O
+.	O
+3	O
+g	O
+/	O
+kg	O
+on	O
+i	O
+.	O
+v	O
+.	O
+)	O
+was	O
+increased	O
+to	O
+5	O
+.	O
+2	O
+g	O
+/	O
+kg	O
+by	O
+oral	O
+administration	O
+.	O
+
+Among	O
+the	O
+few	O
+proteins	O
+of	O
+the	O
+eukaryotic	O
+nucleolus	O
+that	O
+have	O
+been	O
+characterized	O
+,	O
+four	O
+proteins	O
+,	O
+nucleolin	B-GENE
+,	O
+fibrillarin	B-GENE
+,	O
+SSB1	B-GENE
+and	O
+NSR1	B-GENE
+,	O
+possess	O
+a	O
+common	O
+structural	O
+motif	O
+,	O
+the	O
+GAR	O
+domain	O
+,	O
+which	O
+is	O
+rich	O
+in	O
+glycine	O
+and	O
+arginine	O
+residues	O
+.	O
+
+Thus	O
+,	O
+this	O
+study	O
+provides	O
+evidence	O
+that	O
+a	O
+novel	O
+,	O
+ubiquitous	O
+factor	O
+(	O
+HF	B-GENE
+-	I-GENE
+1a	I-GENE
+)	O
+and	O
+a	O
+muscle	O
+factor	O
+(	O
+HF	B-GENE
+-	I-GENE
+1b	I-GENE
+/	O
+MEF	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+can	O
+form	O
+a	O
+novel	O
+,	O
+E	O
+-	O
+box	O
+-	O
+independent	O
+pathway	O
+for	O
+muscle	O
+-	O
+specific	O
+expression	O
+in	O
+ventricular	O
+cardiac	O
+muscle	O
+cells	O
+.	O
+
+Mutations	O
+in	O
+either	O
+gene	O
+block	O
+some	O
+crucial	O
+late	O
+step	O
+in	O
+assembly	O
+of	O
+F1	B-GENE
+,	O
+causing	O
+the	O
+alpha	O
+and	O
+beta	O
+subunits	O
+to	O
+accumulate	O
+in	O
+mitochondria	O
+as	O
+inactive	O
+aggregates	O
+(	O
+Ackerman	O
+,	O
+S	O
+.	O
+
+Expense	O
+limits	O
+the	O
+use	O
+of	O
+hepatitis	O
+B	O
+vaccines	O
+,	O
+but	O
+low	O
+-	O
+dose	O
+intradermal	O
+immunization	O
+has	O
+been	O
+evaluated	O
+as	O
+a	O
+cost	O
+-	O
+saving	O
+strategy	O
+in	O
+numerous	O
+studies	O
+.	O
+
+Estrogen	O
+replacement	O
+therapy	O
+and	O
+risk	O
+of	O
+breast	O
+cancer	O
+:	O
+results	O
+of	O
+two	O
+meta	O
+-	O
+analyses	O
+.	O
+
+Switching	O
+FDC	O
+-	O
+P1	O
+/	O
+MAC	O
+cells	O
+from	O
+growth	O
+in	O
+M	B-GENE
+-	I-GENE
+CSF	I-GENE
+to	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+caused	O
+the	O
+selective	O
+degradation	O
+of	O
+c	B-GENE
+-	I-GENE
+fms	I-GENE
+mRNA	I-GENE
+within	O
+6	O
+h	O
+after	O
+factor	O
+switching	O
+.	O
+
+There	O
+was	O
+however	O
+,	O
+no	O
+significant	O
+difference	O
+in	O
+the	O
+prevalence	O
+of	O
+chronic	O
+respiratory	O
+symptoms	O
+between	O
+animal	O
+food	O
+workers	O
+with	O
+positive	O
+and	O
+negative	O
+skin	O
+tests	O
+to	O
+house	O
+dust	O
+or	O
+to	O
+fish	O
+flour	O
+or	O
+among	O
+those	O
+with	O
+increased	O
+or	O
+normal	O
+IgE	B-GENE
+(	O
+except	O
+for	O
+dyspnea	O
+)	O
+.	O
+
+An	O
+unexpected	O
+finding	O
+was	O
+the	O
+presence	O
+at	O
+position	O
+-	O
+403	O
+to	O
+-	O
+385	O
+of	O
+a	O
+putative	O
+dioxin	O
+responsive	O
+element	O
+,	O
+a	O
+sequence	O
+found	O
+to	O
+be	O
+responsible	O
+for	O
+the	O
+induction	O
+of	O
+transcription	O
+of	O
+the	O
+cytochrome	B-GENE
+P450IA1	I-GENE
+gene	I-GENE
+(	O
+CYPIA1	B-GENE
+)	O
+and	O
+other	O
+genes	O
+involved	O
+in	O
+detoxification	O
+/	O
+activation	O
+of	O
+polycyclic	O
+aromatic	O
+hydrocarbons	O
+.	O
+
+Using	O
+bovine	B-GENE
+and	I-GENE
+murine	I-GENE
+c	I-GENE
+-	I-GENE
+myb	I-GENE
+clones	O
+,	O
+no	O
+change	O
+in	O
+the	O
+rate	O
+of	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+gene	I-GENE
+transcription	O
+or	O
+mRNA	O
+stability	O
+was	O
+detected	O
+during	O
+the	O
+cell	O
+cycle	O
+.	O
+
+A	O
+13	O
+base	O
+-	O
+pair	O
+oligonucleotide	O
+spanning	O
+nucleotides	O
++	O
+80	O
+to	O
++	O
+92	O
+of	O
+the	O
+5	B-GENE
+S	I-GENE
+RNA	I-GENE
+gene	I-GENE
+retained	O
+specific	O
+and	O
+high	O
+-	O
+affinity	O
+binding	O
+,	O
+although	O
+the	O
+latter	O
+was	O
+reduced	O
+sixfold	O
+relative	O
+to	O
+longer	O
+DNA	O
+fragments	O
+.	O
+
+Moreover	O
+,	O
+the	O
+reconstitution	O
+of	O
+eUSF	B-GENE
+and	O
+TFIID	B-GENE
+-	O
+depleted	O
+transcription	O
+complexes	O
+with	O
+purified	O
+protein	O
+fractions	O
+demonstrate	O
+that	O
+not	O
+only	O
+TFIID	B-GENE
+but	O
+also	O
+eUSF	B-GENE
+essentially	O
+participates	O
+in	O
+complex	O
+formation	O
+even	O
+on	O
+H5	B-GENE
+promoter	I-GENE
+mutations	O
+lacking	O
+the	O
+TATA	O
+-	O
+box	O
+.	O
+
+Radiolabelled	O
+palmitate	O
+was	O
+not	O
+incorporated	O
+into	O
+the	O
+mutated	O
+protein	O
+,	O
+showing	O
+that	O
+lipid	O
+modification	O
+occurs	O
+at	O
+the	O
+Cys	O
+-	O
+22	O
+residue	O
+.	O
+
+17	O
+volunteer	O
+deaf	O
+Ss	O
+were	O
+compared	O
+with	O
+18	O
+volunteer	O
+hearing	O
+Ss	O
+on	O
+the	O
+Stanford	O
+Hypnotic	O
+Clinical	O
+Scale	O
+(	O
+SHCS	O
+)	O
+of	O
+Morgan	O
+and	O
+J	O
+.	O
+
+Mature	B-GENE
+tobacco	I-GENE
+L12	I-GENE
+protein	I-GENE
+has	O
+44	O
+%	O
+amino	O
+acid	O
+identity	O
+with	O
+ribosomal	O
+protein	O
+L7	B-GENE
+/	O
+L12	B-GENE
+of	O
+Escherichia	O
+coli	O
+.	O
+
+Nuclear	B-GENE
+-	I-GENE
+encoded	I-GENE
+chloroplast	I-GENE
+ribosomal	I-GENE
+protein	I-GENE
+L12	I-GENE
+of	I-GENE
+Nicotiana	I-GENE
+tabacum	I-GENE
+:	O
+characterization	O
+of	O
+mature	O
+protein	O
+and	O
+isolation	O
+and	O
+sequence	O
+analysis	O
+of	O
+cDNA	O
+clones	O
+encoding	O
+its	O
+cytoplasmic	O
+precursor	O
+.	O
+
+The	O
+gene	O
+encoding	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+was	O
+previously	O
+found	O
+to	O
+contain	O
+an	O
+intronic	O
+enhancer	O
+element	O
+that	O
+was	O
+not	O
+tissue	O
+-	O
+specific	O
+in	O
+its	O
+activity	O
+,	O
+despite	O
+the	O
+restricted	O
+expression	O
+of	O
+the	O
+intact	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+-	I-GENE
+encoding	I-GENE
+gene	I-GENE
+.	O
+
+Molecular	O
+cloning	O
+of	O
+the	O
+polypeptide	O
+component	O
+of	O
+the	O
+Rel	B-GENE
+-	I-GENE
+related	I-GENE
+human	I-GENE
+p75	I-GENE
+nucleoprotein	I-GENE
+complex	I-GENE
+has	O
+revealed	O
+its	O
+identity	O
+with	O
+the	O
+65	O
+-	O
+kDa	O
+(	O
+p65	B-GENE
+)	O
+subunit	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+.	O
+
+Of	O
+the	O
+drugs	O
+orally	O
+administered	O
+,	O
+WR	O
+-	O
+168643	O
+was	O
+the	O
+best	O
+protector	O
+with	O
+a	O
+DMF	O
+of	O
+1	O
+.	O
+51	O
+.	O
+
+Characterization	O
+of	O
+these	O
+R	O
+subunits	O
+by	O
+their	O
+8	O
+-	O
+azido	O
+-	O
+cAMP	O
+photoaffinity	O
+labeling	O
+and	O
+immunoreactivity	O
+,	O
+as	O
+well	O
+as	O
+by	O
+a	O
+phosphorylation	O
+-	O
+dependent	O
+mobility	O
+shift	O
+on	O
+sodium	O
+dodecyl	O
+sulfate	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+(	O
+SDS	O
+-	O
+PAGE	O
+)	O
+,	O
+indicated	O
+subunit	O
+sizes	O
+of	O
+RII	B-GENE
+beta	I-GENE
+(	O
+53	O
+kDa	O
+)	O
+greater	O
+than	O
+RII	B-GENE
+alpha	I-GENE
+dephosphoform	O
+(	O
+51	O
+kDa	O
+)	O
+greater	O
+than	O
+RI	B-GENE
+alpha	I-GENE
+(	O
+49	O
+kDa	O
+)	O
+.	O
+
+Comparison	O
+of	O
+the	O
+genomic	O
+DNA	O
+sequence	O
+with	O
+that	O
+of	O
+the	O
+four	O
+different	O
+mRNAs	O
+indicates	O
+that	O
+these	O
+transcripts	O
+are	O
+produced	O
+by	O
+alternative	O
+splicing	O
+of	O
+the	O
+murine	O
+pre	O
+-	O
+mRNA	O
+according	O
+to	O
+a	O
+cassette	O
+model	O
+.	O
+
+During	O
+the	O
+1980	O
+'	O
+s	O
+,	O
+quantifications	O
+of	O
+immunoserological	O
+testings	O
+,	O
+especially	O
+C	B-GENE
+reactive	I-GENE
+protein	I-GENE
+,	O
+rheumatoid	B-GENE
+factor	I-GENE
+and	O
+antistreptolysin	B-GENE
+O	I-GENE
+,	O
+progressed	O
+rapidly	O
+.	O
+
+Within	O
+the	O
+human	O
+enhancer	O
+,	O
+these	O
+two	O
+sites	O
+are	O
+located	O
+within	O
+the	O
+previously	O
+defined	O
+DNase	B-GENE
+I	I-GENE
+footprints	I-GENE
+,	O
+NFAT	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+NFIL	B-GENE
+-	I-GENE
+2B	I-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+cardiac	B-GENE
+myosin	I-GENE
+light	I-GENE
+chain	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+MLC	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+gene	O
+promoter	O
+contains	O
+several	O
+positive	O
+and	O
+negative	O
+cis	O
+-	O
+acting	O
+sequences	O
+that	O
+are	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+its	O
+expression	O
+.	O
+
+Deletion	O
+mutagenesis	O
+demonstrated	O
+that	O
+these	O
+two	O
+elements	O
+are	O
+involved	O
+in	O
+the	O
+positive	O
+regulation	O
+of	O
+MLC	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+Disruption	O
+mutations	O
+have	O
+been	O
+constructed	O
+in	O
+the	O
+SLK1	B-GENE
+gene	I-GENE
+.	O
+slk1	B-GENE
+null	I-GENE
+mutants	I-GENE
+cannot	O
+grow	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+but	O
+many	O
+cells	O
+can	O
+grow	O
+at	O
+30	O
+,	O
+24	O
+,	O
+and	O
+17	O
+degrees	O
+C	O
+.	O
+
+Molecular	O
+and	O
+genetic	O
+analysis	O
+of	O
+the	O
+yeast	B-GENE
+early	I-GENE
+meiotic	I-GENE
+recombination	I-GENE
+genes	I-GENE
+REC102	I-GENE
+and	O
+REC107	B-GENE
+/	O
+MER2	B-GENE
+.	O
+
+Probable	O
+progressive	O
+multifocal	O
+leukoencephalopathy	O
+(	O
+PML	O
+)	O
+was	O
+diagnosed	O
+on	O
+the	O
+basis	O
+of	O
+clinical	O
+picture	O
+and	O
+magnetic	O
+resonance	O
+imaging	O
+in	O
+a	O
+63	O
+-	O
+year	O
+-	O
+old	O
+man	O
+with	O
+a	O
+complete	O
+remission	O
+of	O
+a	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphoma	O
+.	O
+
+Proprotein	O
+processing	O
+occurs	O
+intracellularly	O
+.	O
+
+A	O
+32P	O
+-	O
+labeled	O
+LAP	B-GENE
+DNA	O
+-	O
+binding	O
+and	O
+dimerization	O
+domain	O
+"	O
+zipper	O
+probe	O
+"	O
+was	O
+used	O
+to	O
+isolate	O
+a	O
+clone	O
+that	O
+encodes	O
+a	O
+new	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+-	I-GENE
+homologous	I-GENE
+protein	I-GENE
+:	O
+CHOP	B-GENE
+-	I-GENE
+10	I-GENE
+.	O
+
+Using	O
+a	O
+degenerate	O
+oligodeoxyribonucleotide	O
+(	O
+oligo	O
+)	O
+based	O
+on	O
+the	O
+N	O
+-	O
+terminal	O
+aa	O
+sequence	O
+,	O
+plus	O
+an	O
+internal	O
+oligo	O
+homologous	O
+to	O
+a	O
+conserved	O
+region	O
+within	O
+the	O
+portion	O
+of	O
+CYP1	B-GENE
+and	O
+CYP2	B-GENE
+that	O
+had	O
+been	O
+deleted	O
+in	O
+the	O
+genome	O
+,	O
+a	O
+CYP3	B-GENE
+-	I-GENE
+specific	I-GENE
+DNA	I-GENE
+fragment	I-GENE
+was	O
+generated	O
+by	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+using	O
+GL81	O
+genomic	O
+DNA	O
+as	O
+a	O
+substrate	O
+.	O
+
+Stringent	O
+hybridization	O
+of	O
+EHS	B-GENE
+-	I-GENE
+1	I-GENE
+back	O
+to	O
+primate	O
+genomic	O
+DNA	O
+indicates	O
+two	O
+distinct	O
+EHS	B-GENE
+-	I-GENE
+1	I-GENE
+loci	I-GENE
+in	O
+normal	O
+human	O
+DNA	O
+,	O
+an	O
+identical	O
+band	O
+pattern	O
+in	O
+chimpanzee	O
+DNA	O
+,	O
+and	O
+a	O
+single	O
+locus	O
+in	O
+rhesus	O
+monkey	O
+DNA	O
+.	O
+
+The	O
+level	O
+of	O
+carboxyl	B-GENE
+-	I-GENE
+terminal	I-GENE
+parathyroid	I-GENE
+hormone	I-GENE
+in	O
+the	O
+patients	O
+with	O
+thyroid	O
+carcinoma	O
+was	O
+higher	O
+than	O
+that	O
+in	O
+the	O
+patients	O
+without	O
+thyroid	O
+carcinoma	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+Caenorhabditis	B-GENE
+elegans	I-GENE
+vitellogenin	I-GENE
+genes	I-GENE
+are	O
+subject	O
+to	O
+sex	O
+-	O
+,	O
+stage	O
+-	O
+,	O
+and	O
+tissue	O
+-	O
+specific	O
+regulation	O
+:	O
+they	O
+are	O
+expressed	O
+solely	O
+in	O
+the	O
+adult	O
+hermaphrodite	O
+intestine	O
+.	O
+
+The	O
+functions	O
+of	O
+isolated	O
+portions	O
+of	O
+the	O
+insulin	B-GENE
+,	O
+IAPP	B-GENE
+,	O
+and	O
+beta	B-GENE
+GK	I-GENE
+promoters	I-GENE
+were	O
+studied	O
+by	O
+using	O
+transient	O
+expression	O
+and	O
+DNA	O
+binding	O
+assays	O
+.	O
+
+The	O
+c	B-GENE
+-	I-GENE
+Ets	I-GENE
+-	I-GENE
+1	I-GENE
+oncoprotein	I-GENE
+is	O
+a	O
+transcription	O
+activator	O
+that	O
+specifically	O
+binds	O
+to	O
+DNA	O
+.	O
+
+Previous	O
+transactivation	O
+experiments	O
+indicated	O
+that	O
+three	O
+amino	O
+acids	O
+residing	O
+in	O
+this	O
+region	O
+,	O
+Gly	O
+,	O
+Ser	O
+and	O
+Val	O
+,	O
+appear	O
+to	O
+be	O
+critical	O
+for	O
+target	O
+-	O
+site	O
+discrimination	O
+.	O
+
+GR63178A	O
+is	O
+a	O
+water	O
+-	O
+soluble	O
+analogue	O
+of	O
+mitoquidone	O
+,	O
+a	O
+pentacyclic	O
+pyrroloquinone	O
+.	O
+
+Marker	O
+rescue	O
+analysis	O
+has	O
+localized	O
+ts8	B-GENE
+to	O
+a	O
+910	O
+-	O
+bp	O
+internal	O
+segment	O
+of	O
+rpoB	B-GENE
+that	O
+encodes	O
+the	O
+Rif	B-GENE
+domain	I-GENE
+.	O
+
+This	O
+vector	O
+transfected	O
+into	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+directs	O
+expression	O
+of	O
+a	O
+secreted	O
+mature	O
+protein	O
+at	O
+levels	O
+up	O
+to	O
+200	O
+mg	O
+of	O
+LAPP	O
+/	O
+liter	O
+of	O
+culture	O
+medium	O
+.	O
+
+Competition	O
+analysis	O
+by	O
+gel	O
+mobility	O
+shift	O
+electrophoresis	O
+indicates	O
+that	O
+this	O
+DNA	O
+-	O
+protein	O
+interaction	O
+is	O
+novel	O
+and	O
+not	O
+related	O
+to	O
+many	O
+transcription	O
+factors	O
+previously	O
+reported	O
+.	O
+
+This	O
+DNA	O
+motif	O
+represents	O
+a	O
+novel	O
+protein	O
+-	O
+binding	O
+sequence	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+study	O
+was	O
+designed	O
+to	O
+investigate	O
+the	O
+frequency	O
+of	O
+alterations	O
+in	O
+serum	O
+creatinine	O
+in	O
+patients	O
+with	O
+psoriasis	O
+receiving	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+of	O
+cyclosporine	O
+.	O
+
+Intrapocket	O
+chemotherapy	O
+in	O
+adult	O
+periodontitis	O
+using	O
+a	O
+new	O
+controlled	O
+-	O
+release	O
+insert	O
+containing	O
+ofloxacin	O
+(	O
+PT	O
+-	O
+01	O
+)	O
+.	O
+
+Electromagnetic	O
+blood	O
+flow	O
+(	O
+BF	O
+)	O
+probe	O
+was	O
+applied	O
+on	O
+the	O
+left	O
+anterior	O
+descending	O
+artery	O
+(	O
+LAD	O
+)	O
+.	O
+
+Hence	O
+temperature	O
+and	O
+virF	B-GENE
+are	O
+both	O
+required	O
+for	O
+the	O
+induction	O
+of	O
+the	O
+yop	B-GENE
+regulon	I-GENE
+.	O
+
+Problems	O
+remain	O
+to	O
+be	O
+resolved	O
+in	O
+the	O
+area	O
+of	O
+quantitative	O
+risk	O
+assessment	O
+.	O
+
+The	O
+Klebsiella	B-GENE
+aerogenes	I-GENE
+gene	I-GENE
+maoA	I-GENE
+,	O
+which	O
+is	O
+involved	O
+in	O
+the	O
+synthesis	O
+of	O
+monoamine	B-GENE
+oxidase	I-GENE
+,	O
+was	O
+induced	O
+by	O
+tyramine	O
+and	O
+the	O
+related	O
+compounds	O
+,	O
+subjected	O
+to	O
+catabolite	O
+and	O
+ammonium	O
+ion	O
+repression	O
+,	O
+and	O
+cloned	O
+.	O
+
+Eight	O
+of	O
+14	O
+infectious	O
+or	O
+inflammatory	O
+lesions	O
+could	O
+be	O
+detected	O
+in	O
+the	O
+early	O
+scan	O
+(	O
+4	O
+-	O
+6	O
+h	O
+p	O
+.	O
+i	O
+.	O
+)	O
+.	O
+
+Similar	O
+observations	O
+have	O
+been	O
+made	O
+previously	O
+for	O
+other	O
+genes	O
+.	O
+
+Preceptorship	O
+of	O
+CNS	O
+students	O
+:	O
+an	O
+exploratory	O
+study	O
+.	O
+
+To	O
+determine	O
+the	O
+genetic	O
+basis	O
+for	O
+the	O
+differences	O
+between	O
+the	O
+cardiac	O
+and	O
+brain	B-GENE
+AE3	I-GENE
+variants	I-GENE
+,	O
+we	O
+isolated	O
+and	O
+characterized	O
+the	O
+rat	O
+gene	O
+.	O
+
+The	O
+1	O
+.	O
+7	O
+kb	O
+cloned	O
+fragment	O
+was	O
+sequenced	O
+and	O
+shown	O
+to	O
+contain	O
+the	O
+entire	O
+fliA	B-GENE
+gene	I-GENE
+.	O
+
+Institution	O
+of	O
+both	O
+intravenous	O
+and	O
+intracisternal	O
+administration	O
+of	O
+amphotericin	O
+B	O
+and	O
+possibly	O
+concomitant	O
+intravenous	O
+administration	O
+of	O
+dexamethasone	O
+may	O
+be	O
+warranted	O
+in	O
+situations	O
+in	O
+which	O
+the	O
+association	O
+of	O
+C	O
+.	O
+immitis	O
+with	O
+CNS	O
+vasculitis	O
+or	O
+encephalitis	O
+appears	O
+likely	O
+before	O
+serologic	O
+or	O
+cultural	O
+confirmation	O
+of	O
+C	O
+.	O
+immitis	O
+infection	O
+involving	O
+the	O
+CNS	O
+is	O
+available	O
+.	O
+
+Lac	B-GENE
+operators	O
+were	O
+introduced	O
+into	O
+several	O
+positions	O
+within	O
+the	O
+CAB	B-GENE
+promoter	I-GENE
+and	O
+operator	O
+-	O
+free	O
+plasmid	O
+was	O
+used	O
+as	O
+control	O
+.	O
+
+Overproduction	O
+,	O
+purification	O
+and	O
+characterization	O
+of	O
+M	B-GENE
+.	I-GENE
+HinfI	I-GENE
+methyltransferase	I-GENE
+and	O
+its	O
+deletion	O
+mutant	O
+.	O
+
+Various	O
+companies	O
+produce	O
+this	O
+type	O
+of	O
+lens	O
+.	O
+
+From	O
+March	O
+5	O
+through	O
+October	O
+26	O
+,	O
+1991	O
+,	O
+eight	O
+persons	O
+were	O
+diagnosed	O
+with	O
+elevated	O
+blood	O
+lead	O
+levels	O
+(	O
+BLLs	O
+)	O
+at	O
+a	O
+local	O
+hospital	O
+and	O
+were	O
+reported	O
+to	O
+the	O
+notifiable	O
+disease	O
+surveillance	O
+system	O
+maintained	O
+by	O
+the	O
+Alabama	O
+Department	O
+of	O
+Public	O
+Health	O
+(	O
+ADPH	O
+)	O
+.	O
+
+According	O
+to	O
+the	O
+changes	O
+of	O
+perfusion	O
+defects	O
+between	O
+Ex	O
+,	O
+RD	O
+and	O
+ReI	O
+images	O
+,	O
+they	O
+were	O
+classified	O
+into	O
+3	O
+types	O
+:	O
+Type	O
+I	O
+;	O
+perfusion	O
+defect	O
+on	O
+the	O
+RD	O
+image	O
+was	O
+identical	O
+to	O
+ReI	O
+image	O
+(	O
+75	O
+%	O
+)	O
+Type	O
+I	O
+was	O
+divided	O
+into	O
+2	O
+subgroups	O
+whether	O
+perfusion	O
+defect	O
+at	O
+Ex	O
+was	O
+unchanged	O
+(	O
+Ia	O
+,	O
+42	O
+%	O
+)	O
+or	O
+improved	O
+(	O
+Ib	O
+,	O
+33	O
+%	O
+)	O
+on	O
+the	O
+RD	O
+image	O
+.	O
+
+Keck	O
+,	O
+C	O
+.	O
+J	O
+.	O
+
+Twenty	O
+-	O
+eight	O
+(	O
+7	O
+.	O
+0	O
+%	O
+)	O
+infants	O
+without	O
+periventricular	O
+hemorrhage	O
+were	O
+revealed	O
+as	O
+having	O
+spastic	O
+cerebral	O
+palsy	O
+by	O
+neurodevelopmental	O
+evaluation	O
+in	O
+later	O
+infancy	O
+.	O
+
+A	O
+possible	O
+mechanism	O
+is	O
+that	O
+elevated	O
+alveolar	O
+pressure	O
+and	O
+decreased	O
+cardiac	O
+output	O
+eliminate	O
+blood	O
+flow	O
+from	O
+corner	O
+vessels	O
+in	O
+nondependent	O
+high	O
+VA	O
+/	O
+Q	O
+regions	O
+.	O
+
+In	O
+both	O
+cities	O
+,	O
+HTLV	O
+-	O
+I	O
+/	O
+II	O
+prevalence	O
+increased	O
+significantly	O
+with	O
+age	O
+,	O
+and	O
+the	O
+New	O
+Orleans	O
+age	O
+-	O
+and	O
+sex	O
+-	O
+adjusted	O
+HTLV	O
+-	O
+I	O
+/	O
+II	O
+prevalence	O
+was	O
+significantly	O
+higher	O
+than	O
+that	O
+of	O
+Baltimore	O
+(	O
+P	O
+less	O
+than	O
+.	O
+001	O
+)	O
+.	O
+
+Hybridization	O
+data	O
+indicate	O
+that	O
+6F6	B-GENE
+.	I-GENE
+2	I-GENE
+corresponds	O
+to	O
+the	O
+previously	O
+characterized	O
+m6F6	B-GENE
+cDNA	I-GENE
+clone	I-GENE
+and	O
+that	O
+6F6	B-GENE
+.	I-GENE
+1	I-GENE
+and	O
+6F6	B-GENE
+.	I-GENE
+3	I-GENE
+,	O
+but	O
+not	O
+6F6	B-GENE
+.	I-GENE
+2	I-GENE
+,	O
+are	O
+adjacent	O
+to	O
+alpha	B-GENE
+-	I-GENE
+type	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+SEN1	B-GENE
+gene	I-GENE
+corresponds	O
+to	O
+a	O
+6	O
+,	O
+336	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+coding	O
+for	O
+a	O
+2	O
+,	O
+112	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+(	O
+molecular	O
+mass	O
+,	O
+239	O
+kDa	O
+)	O
+.	O
+
+Protein	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+(	O
+PTKs	B-GENE
+)	O
+are	O
+implicated	O
+in	O
+the	O
+control	O
+of	O
+cell	O
+growth	O
+by	O
+virtue	O
+of	O
+their	O
+frequent	O
+appearance	O
+as	O
+products	O
+of	O
+retroviral	O
+oncogenes	O
+,	O
+as	O
+intracellular	O
+signal	O
+transducers	O
+,	O
+and	O
+as	O
+growth	B-GENE
+factor	I-GENE
+receptors	I-GENE
+or	O
+components	O
+thereof	O
+.	O
+
+The	O
+IA4	B-GENE
+mAb	I-GENE
+was	O
+identified	O
+among	O
+a	O
+series	O
+of	O
+antibodies	O
+raised	O
+in	O
+BALB	O
+/	O
+c	O
+mice	O
+after	O
+immunization	O
+against	O
+a	O
+HLA	B-GENE
+class	O
+I	O
+-	O
+deficient	O
+,	O
+lymphokine	O
+-	O
+activated	O
+killer	O
+(	O
+LAK	O
+)	O
+-	O
+susceptible	O
+EBV	O
+-	O
+B	O
+lymphocyte	O
+line	O
+.	O
+
+In	O
+a	O
+randomized	O
+double	O
+-	O
+blind	O
+cross	O
+-	O
+over	O
+study	O
+,	O
+the	O
+subjects	O
+received	O
+theophylline	O
+5	O
+mg	O
+.	O
+kg	O
+-	O
+1	O
+per	O
+day	O
+with	O
+omeprazole	O
+20	O
+mg	O
+per	O
+day	O
+or	O
+identical	O
+placebo	O
+during	O
+two	O
+periods	O
+,	O
+each	O
+of	O
+7	O
+days	O
+,	O
+separated	O
+by	O
+a	O
+washout	O
+period	O
+of	O
+7	O
+days	O
+.	O
+
+Primer	O
+extension	O
+and	O
+mung	B-GENE
+bean	I-GENE
+and	I-GENE
+S1	I-GENE
+nuclease	I-GENE
+mapping	O
+indicated	O
+multiple	O
+transcription	O
+initiation	O
+sites	O
+and	O
+were	O
+consistent	O
+with	O
+Northern	O
+analyses	O
+.	O
+
+Two	O
+variant	O
+PRP	B-GENE
+-	I-GENE
+precursor	I-GENE
+alleles	I-GENE
+occur	O
+which	O
+slightly	O
+differ	O
+in	O
+the	O
+number	O
+of	O
+repeats	O
+in	O
+domain	O
+C	O
+.	O
+
+Unlike	O
+the	O
+typical	O
+enhancer	O
+element	O
+,	O
+this	O
+region	O
+functions	O
+in	O
+an	O
+orientation	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Allagille	O
+'	O
+s	O
+syndrome	O
+associated	O
+with	O
+antenatal	O
+ascites	O
+
+Sensitivity	O
+and	O
+specificity	O
+was	O
+established	O
+for	O
+the	O
+Pharmacia	O
+CAP	O
+System	O
+and	O
+the	O
+DPC	O
+AlaSTAT	O
+System	O
+by	O
+comparison	O
+with	O
+results	O
+of	O
+the	O
+skin	O
+prick	O
+test	O
+.	O
+
+PSI	B-GENE
+-	I-GENE
+G	I-GENE
+and	O
+PSI	B-GENE
+-	I-GENE
+K	I-GENE
+probably	O
+have	O
+evolved	O
+from	O
+a	O
+gene	O
+duplication	O
+of	O
+an	O
+ancestral	O
+gene	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+revealed	O
+that	O
+two	O
+clusters	O
+of	O
+basic	O
+amino	O
+acids	O
+within	O
+a	O
+conserved	O
+basic	O
+region	O
+and	O
+two	O
+amphipathic	O
+helices	O
+within	O
+the	O
+adjacent	O
+HLH	O
+domain	O
+are	O
+essential	O
+for	O
+sequence	O
+-	O
+specific	O
+DNA	O
+binding	O
+and	O
+hetero	O
+-	O
+oligomerization	O
+,	O
+respectively	O
+.	O
+
+Dimerization	O
+of	O
+Myf	B-GENE
+-	I-GENE
+5	I-GENE
+with	O
+the	O
+ubiquitously	O
+expressed	O
+bHLH	O
+protein	O
+E12	B-GENE
+not	O
+only	O
+increases	O
+the	O
+affinity	O
+for	O
+DNA	O
+but	O
+also	O
+stimulates	O
+transactivation	O
+independently	O
+of	O
+DNA	O
+binding	O
+.	O
+
+SEA	O
+was	O
+recorded	O
+with	O
+bidirectional	O
+filters	O
+at	O
+25	O
+-	O
+250	O
+HZ	O
+and	O
+40	O
+-	O
+250	O
+Hz	O
+using	O
+Simson	O
+method	O
+.	O
+
+Neural	O
+-	O
+specific	O
+expression	O
+,	O
+genomic	O
+structure	O
+,	O
+and	O
+chromosomal	O
+localization	O
+of	O
+the	O
+gene	O
+encoding	O
+the	O
+zinc	B-GENE
+-	I-GENE
+finger	I-GENE
+transcription	I-GENE
+factor	I-GENE
+NGFI	I-GENE
+-	I-GENE
+C	I-GENE
+.	O
+
+An	O
+experiment	O
+examined	O
+the	O
+effects	O
+of	O
+treatment	O
+with	O
+gonadotrophin	B-GENE
+releasing	I-GENE
+hormone	I-GENE
+(	O
+100	O
+micrograms	O
+GnRH	B-GENE
+injected	O
+24	O
+h	O
+after	O
+progestagen	O
+sponge	O
+removal	O
+)	O
+,	O
+season	O
+of	O
+treatment	O
+(	O
+autumn	O
+v	O
+.	O
+spring	O
+)	O
+,	O
+the	O
+effect	O
+of	O
+supplementary	O
+feeding	O
+with	O
+lupin	O
+grain	O
+(	O
+in	O
+autumn	O
+only	O
+,	O
+from	O
+12	O
+days	O
+before	O
+until	O
+8	O
+days	O
+after	O
+sponge	O
+removal	O
+)	O
+on	O
+the	O
+time	O
+of	O
+ovulation	O
+in	O
+182	O
+mature	O
+Merino	O
+ewes	O
+superovulated	O
+with	O
+a	O
+combination	O
+of	O
+400	O
+I	O
+.	O
+U	O
+.	O
+pregnant	B-GENE
+mare	I-GENE
+serum	I-GENE
+gonadotrophin	I-GENE
+(	O
+PMSG	B-GENE
+)	O
+and	O
+12	O
+mg	O
+follicle	B-GENE
+stimulating	I-GENE
+hormone	I-GENE
+(	O
+FSH	B-GENE
+-	I-GENE
+P	I-GENE
+)	O
+.	O
+
+Drug	O
+-	O
+drug	O
+interactions	O
+are	O
+most	O
+likely	O
+to	O
+occur	O
+in	O
+patients	O
+receiving	O
+multiple	O
+medications	O
+and	O
+with	O
+drugs	O
+that	O
+have	O
+a	O
+narrow	O
+therapeutic	O
+window	O
+.	O
+
+Total	O
+body	O
+irradiation	O
+was	O
+delivered	O
+according	O
+to	O
+a	O
+hyperfractionated	O
+scheme	O
+of	O
+12	O
+fractions	O
+given	O
+three	O
+per	O
+day	O
+5	O
+hr	O
+apart	O
+for	O
+4	O
+days	O
+.	O
+
+A	O
+reduction	O
+in	O
+blood	O
+pressure	O
+was	O
+only	O
+observed	O
+at	O
+the	O
+end	O
+of	O
+the	O
+study	O
+,	O
+from	O
+142	O
++	O
+/	O
+-	O
+17	O
+/	O
+86	O
+.	O
+6	O
++	O
+/	O
+-	O
+9	O
+.	O
+1	O
+to	O
+139	O
++	O
+/	O
+-	O
+13	O
+/	O
+82	O
+.	O
+9	O
++	O
+/	O
+-	O
+8	O
+.	O
+9	O
+mmHg	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+for	O
+DBP	O
+)	O
+.	O
+
+A	O
+gene	O
+homologous	O
+to	O
+the	O
+Escherichia	B-GENE
+coli	I-GENE
+dnaA	I-GENE
+gene	I-GENE
+was	O
+isolated	O
+from	O
+Pseudomonas	O
+putida	O
+and	O
+its	O
+transcription	O
+was	O
+investigated	O
+in	O
+E	O
+.	O
+coli	O
+as	O
+well	O
+as	O
+in	O
+P	O
+.	O
+putida	O
+.	O
+
+STP1	B-GENE
+is	O
+an	O
+unessential	O
+yeast	O
+gene	O
+involved	O
+in	O
+the	O
+removal	O
+of	O
+intervening	O
+sequences	O
+from	O
+some	O
+,	O
+but	O
+not	O
+all	O
+,	O
+families	O
+of	O
+intervening	O
+sequence	O
+-	O
+containing	O
+pre	O
+-	O
+tRNAs	O
+.	O
+
+Using	O
+these	O
+antibodies	O
+,	O
+we	O
+were	O
+able	O
+to	O
+define	O
+the	O
+conditions	O
+to	O
+completely	O
+solubilize	O
+the	O
+Cdc25	B-GENE
+protein	I-GENE
+.	O
+
+GCR1	B-GENE
+gene	I-GENE
+function	O
+is	O
+required	O
+for	O
+high	O
+-	O
+level	O
+glycolytic	O
+gene	O
+expression	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+The	O
+decay	O
+curves	O
+of	O
+chlorophyll	O
+fluorescence	O
+showed	O
+a	O
+superposition	O
+of	O
+three	O
+exponentially	O
+decaying	O
+components	O
+with	O
+time	O
+constants	O
+of	O
+T1	O
+=	O
+100	O
+-	O
+200	O
+ps	O
+,	O
+T2	O
+=	O
+300	O
+-	O
+500	O
+ps	O
+and	O
+T3	O
+=	O
+2	O
+.	O
+0	O
+-	O
+3	O
+.	O
+5	O
+ns	O
+.	O
+
+After	O
+tilting	O
+,	O
+systolic	O
+blood	O
+pressure	O
+fell	O
+an	O
+average	O
+of	O
+17	O
+%	O
+in	O
+patients	O
+who	O
+cramped	O
+infrequently	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0031	O
+)	O
+but	O
+only	O
+10	O
+%	O
+in	O
+frequently	O
+cramping	O
+patients	O
+.	O
+
+Most	O
+apneic	O
+events	O
+occurred	O
+during	O
+Stages	O
+I	O
+and	O
+II	O
+,	O
+and	O
+REM	O
+,	O
+but	O
+this	O
+proportion	O
+was	O
+less	O
+during	O
+the	O
+gamma	O
+OH	O
+study	O
+(	O
+77	O
+.	O
+9	O
++	O
+/	O
+-	O
+8	O
+.	O
+9	O
+%	O
+)	O
+than	O
+during	O
+the	O
+control	O
+studies	O
+(	O
+92	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+and	O
+95	O
+.	O
+9	O
++	O
+/	O
+-	O
+2	O
+.	O
+2	O
+%	O
+)	O
+,	O
+apneas	O
+occurring	O
+even	O
+during	O
+SWS	O
+with	O
+gamma	O
+OH	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Eight	O
+rabbits	O
+were	O
+exposed	O
+to	O
+0	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+4	O
+mg	O
+/	O
+m3	O
+Co2	O
++	O
+as	O
+CoCl2	O
+and	O
+1	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+mg	O
+/	O
+m3	O
+Cr3	O
++	O
+as	O
+Cr	O
+(	O
+NO3	O
+)	O
+3	O
+(	O
+group	O
+Co	O
++	O
+Cr	O
+)	O
+,	O
+eight	O
+to	O
+0	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+m3	O
+Co2	O
++	O
+(	O
+group	O
+Co	O
+)	O
+,	O
+and	O
+eight	O
+to	O
+filtered	O
+air	O
+(	O
+control	O
+group	O
+)	O
+,	O
+for	O
+4	O
+months	O
+,	O
+5	O
+days	O
+/	O
+week	O
+,	O
+and	O
+6	O
+hr	O
+/	O
+day	O
+.	O
+
+16	O
+women	O
+were	O
+treated	O
+with	O
+methadone	O
+to	O
+prevent	O
+withdrawal	O
+symptoms	O
+.	O
+
+Disruption	O
+demonstrates	O
+that	O
+CDC14	B-GENE
+is	O
+an	O
+essential	O
+gene	O
+.	O
+
+Coronary	O
+flow	O
+was	O
+reduced	O
+by	O
+10	O
+%	O
+in	O
+the	O
+phosphocreatine	O
+and	O
+by	O
+18	O
+%	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+The	O
+60A	B-GENE
+transcripts	I-GENE
+and	O
+protein	O
+are	O
+first	O
+detected	O
+at	O
+the	O
+onset	O
+of	O
+gastrulation	O
+,	O
+primarily	O
+in	O
+the	O
+mesoderm	O
+of	O
+the	O
+extending	O
+germ	O
+band	O
+.	O
+
+Influence	O
+of	O
+neural	O
+regulation	O
+on	O
+anti	O
+-	O
+arrhythmic	O
+effects	O
+of	O
+GABA	O
+in	O
+rats	O
+
+Recent	O
+investigations	O
+have	O
+detailed	O
+a	O
+selective	O
+dye	O
+release	O
+technique	O
+in	O
+which	O
+a	O
+pulse	O
+of	O
+laser	O
+light	O
+induces	O
+the	O
+release	O
+of	O
+a	O
+fluorescent	O
+dye	O
+from	O
+temperature	O
+-	O
+sensitive	O
+liposomes	O
+circulating	O
+in	O
+the	O
+retinal	O
+vasculature	O
+.	O
+
+And	O
+the	O
+natural	O
+barriers	O
+?	O
+
+Three	O
+pyridoxine	O
+derivatives	O
+have	O
+been	O
+isolated	O
+from	O
+the	O
+fresh	O
+stem	O
+bark	O
+of	O
+Albizzia	O
+julibrissin	O
+DURAZZ	O
+.	O
+.	O
+
+The	O
+coating	O
+materials	O
+were	O
+poloxamine	O
+904	O
+,	O
+poloxamine	O
+908	O
+,	O
+poloxamine	O
+1508	O
+,	O
+poloxamer	O
+338	O
+,	O
+and	O
+Brij	O
+35	O
+.	O
+
+The	O
+eating	O
+and	O
+drinking	O
+patterns	O
+of	O
+pygmy	O
+goats	O
+fed	O
+ad	O
+lib	O
+and	O
+kept	O
+on	O
+a	O
+12	O
+h	O
+light	O
+/	O
+12	O
+h	O
+dark	O
+cycle	O
+were	O
+recorded	O
+and	O
+analyzed	O
+.	O
+
+The	O
+present	O
+study	O
+highlights	O
+the	O
+improvement	O
+in	O
+sputum	O
+amoxycillin	O
+(	O
+amoxy	O
+)	O
+levels	O
+when	O
+a	O
+combination	O
+tablet	O
+,	O
+amoxy	O
+500	O
+mg	O
+plus	O
+bromhexeine	O
+8	O
+mg	O
+,	O
+is	O
+administered	O
+as	O
+compared	O
+to	O
+plain	O
+amoxy	O
+500	O
+mg	O
+.	O
+
+His	O
+HC	B-GENE
+II	I-GENE
+activity	O
+and	O
+antigen	O
+levels	O
+were	O
+49	O
+%	O
+and	O
+50	O
+%	O
+,	O
+respectively	O
+,	O
+and	O
+his	O
+daughter	O
+also	O
+showed	O
+similar	O
+low	O
+levels	O
+.	O
+
+Argatroban	O
+may	O
+be	O
+more	O
+effective	O
+under	O
+low	O
+HC	B-GENE
+II	I-GENE
+conditions	O
+because	O
+of	O
+its	O
+potent	O
+inhibition	O
+of	O
+thrombin	B-GENE
+activity	O
+at	O
+sites	O
+of	O
+vascular	O
+wall	O
+damage	O
+.	O
+
+Because	O
+the	O
+adrenergic	O
+nervous	O
+system	O
+influences	O
+cardiac	O
+arrhythmias	O
+and	O
+myocardial	O
+infarction	O
+can	O
+directly	O
+affect	O
+sympathetic	O
+innervation	O
+in	O
+the	O
+heart	O
+,	O
+we	O
+investigated	O
+the	O
+role	O
+of	O
+the	O
+sympathetic	O
+nervous	O
+system	O
+on	O
+reentry	O
+in	O
+the	O
+canine	O
+heart	O
+4	O
+days	O
+after	O
+infarction	O
+.	O
+
+Furthermore	O
+,	O
+no	O
+transcripts	O
+of	O
+the	O
+same	O
+size	O
+and	O
+having	O
+the	O
+same	O
+developmental	O
+profile	O
+as	O
+those	O
+generated	O
+by	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+E10	I-GENE
+fragment	I-GENE
+were	O
+identified	O
+by	O
+probes	O
+covering	O
+the	O
+remainder	O
+of	O
+the	O
+cloned	O
+region	O
+.	O
+
+Intravenous	O
+amine	O
+pressor	O
+tests	O
+in	O
+healthy	O
+volunteers	O
+.	O
+
+The	O
+mean	O
+minimum	O
+steady	O
+-	O
+state	O
+concentration	O
+after	O
+the	O
+oral	O
+regimen	O
+(	O
+23	O
+micrograms	O
+.	O
+l	O
+-	O
+1	O
+)	O
+was	O
+78	O
+%	O
+of	O
+that	O
+after	O
+the	O
+intramuscular	O
+regime	O
+(	O
+29	O
+micrograms	O
+.	O
+l	O
+-	O
+1	O
+)	O
+.	O
+
+In	O
+an	O
+ongoing	O
+study	O
+the	O
+performance	O
+of	O
+the	O
+SMSP	O
+is	O
+being	O
+compared	O
+with	O
+that	O
+of	O
+the	O
+Mini	O
+Speech	O
+Processor	O
+(	O
+MSP	O
+)	O
+.	O
+
+These	O
+mutant	O
+proteins	O
+retained	O
+the	O
+ability	O
+to	O
+competitively	O
+inhibit	O
+kappa	B-GENE
+B	I-GENE
+-	O
+mediated	O
+transcriptional	O
+activation	O
+of	O
+the	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+but	O
+failed	O
+to	O
+efficiently	O
+transform	O
+chicken	O
+lymphoid	O
+cells	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+The	O
+sequence	O
+-	O
+specific	O
+interaction	O
+of	O
+nuclear	B-GENE
+factor	I-GENE
+HiNF	I-GENE
+-	I-GENE
+D	I-GENE
+with	O
+this	O
+key	O
+proximal	O
+promoter	O
+element	O
+of	O
+the	O
+H4	B-GENE
+-	I-GENE
+FO108	I-GENE
+gene	I-GENE
+is	O
+cell	O
+cycle	O
+regulated	O
+in	O
+normal	O
+diploid	O
+cells	O
+(	O
+J	O
+.	O
+
+In	O
+conclusion	O
+,	O
+to	O
+study	O
+and	O
+overcome	O
+TI	O
+region	O
+-	O
+based	O
+expression	O
+problems	O
+it	O
+is	O
+worthwhile	O
+to	O
+start	O
+out	O
+with	O
+a	O
+versatile	O
+vector	O
+containing	O
+exhaustive	O
+mutations	O
+in	O
+the	O
+periShine	O
+-	O
+Dalgarno	O
+sequences	O
+;	O
+as	O
+a	O
+rule	O
+the	O
+coding	O
+MTI	O
+subregion	O
+can	O
+be	O
+kept	O
+unchanged	O
+.	O
+
+Four	O
+of	O
+these	O
+five	O
+subjects	O
+also	O
+performed	O
+mixed	O
+sequences	O
+under	O
+conditional	O
+control	O
+of	O
+the	O
+words	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+A1	O
+-	O
+-	O
+-	O
+-	O
+B2	O
+-	O
+-	O
+-	O
+-	O
+A3	O
+-	O
+-	O
+-	O
+-	O
+B4	O
+-	O
+-	O
+-	O
+-	O
+A5	O
+and	O
+its	O
+reversal	O
+)	O
+,	O
+verifying	O
+that	O
+the	O
+stimuli	O
+which	O
+occupied	O
+the	O
+same	O
+position	O
+in	O
+each	O
+sequence	O
+were	O
+members	O
+of	O
+the	O
+same	O
+class	O
+.	O
+
+While	O
+blood	O
+pressure	O
+and	O
+noradrenergic	O
+activity	O
+,	O
+assessed	O
+as	O
+changes	O
+in	O
+the	O
+plasma	O
+levels	O
+and	O
+urinary	O
+excretion	O
+of	O
+norepinephrine	O
+,	O
+remained	O
+unaffected	O
+in	O
+the	O
+Pl	O
+group	O
+,	O
+a	O
+significant	O
+drop	O
+in	O
+the	O
+supine	O
+systolic	O
+and	O
+diastolic	O
+blood	O
+pressures	O
+,	O
+as	O
+well	O
+as	O
+in	O
+the	O
+resting	O
+venous	O
+norepinephrine	O
+level	O
+and	O
+in	O
+urinary	O
+norepinephrine	O
+excretion	O
+was	O
+found	O
+after	O
+the	O
+first	O
+month	O
+of	O
+dF	O
+administration	O
+.	O
+
+Wild	O
+-	O
+type	O
+protein	O
+bound	O
+azido	O
+-	O
+ATP	O
+well	O
+,	O
+but	O
+mutants	O
+with	O
+substitutions	O
+in	O
+the	O
+consensus	O
+amino	O
+acids	O
+were	O
+unable	O
+to	O
+bind	O
+azido	O
+-	O
+ATP	O
+.	O
+
+Therefore	O
+,	O
+with	O
+a	O
+biopsy	O
+from	O
+the	O
+stoma	O
+site	O
+there	O
+is	O
+a	O
+risk	O
+of	O
+missing	O
+early	O
+rejection	O
+.	O
+
+Whole	O
+blood	O
+serotonin	O
+levels	O
+were	O
+investigated	O
+in	O
+a	O
+control	O
+group	O
+(	O
+n	O
+=	O
+35	O
+)	O
+and	O
+in	O
+a	O
+group	O
+of	O
+chronic	O
+renal	O
+failure	O
+patients	O
+(	O
+n	O
+=	O
+127	O
+)	O
+on	O
+various	O
+treatment	O
+regimen	O
+i	O
+.	O
+e	O
+.	O
+conservative	O
+treatment	O
+(	O
+n	O
+=	O
+39	O
+)	O
+,	O
+maintenance	O
+haemodialysis	O
+(	O
+n	O
+=	O
+35	O
+)	O
+and	O
+after	O
+renal	O
+transplantation	O
+(	O
+n	O
+=	O
+53	O
+)	O
+.	O
+
+Tissues	O
+and	O
+exudates	O
+contain	O
+sufficient	O
+thymidine	O
+for	O
+growth	O
+of	O
+anaerobic	O
+bacteria	O
+in	O
+the	O
+presence	O
+of	O
+inhibitory	O
+levels	O
+of	O
+trimethoprim	O
+-	O
+sulfamethoxazole	O
+.	O
+
+The	O
+homologies	O
+between	O
+RAD16	B-GENE
+,	O
+RAD54	B-GENE
+and	O
+SNF2	B-GENE
+are	O
+also	O
+shared	O
+by	O
+several	O
+additional	O
+,	O
+recently	O
+isolated	O
+yeast	O
+and	O
+Drosophila	O
+genes	O
+.	O
+
+But	O
+the	O
+application	O
+solutions	O
+of	O
+instrument	O
+disinfectants	O
+should	O
+not	O
+be	O
+used	O
+longer	O
+than	O
+one	O
+day	O
+.	O
+
+In	O
+the	O
+Rett	O
+syndrome	O
+we	O
+,	O
+therefore	O
+,	O
+suspect	O
+there	O
+are	O
+disturbances	O
+in	O
+the	O
+brain	O
+stem	O
+functions	O
+especially	O
+in	O
+the	O
+ascending	O
+reticular	O
+activating	O
+system	O
+which	O
+is	O
+related	O
+to	O
+elevation	O
+of	O
+the	O
+conscious	O
+level	O
+.	O
+
+In	O
+a	O
+similar	O
+experiment	O
+,	O
+simultaneous	O
+nitrofurazone	O
+administration	O
+and	O
+S	O
+.	O
+enteritidis	O
+challenge	O
+resulted	O
+in	O
+no	O
+significant	O
+differences	O
+in	O
+S	O
+.	O
+enteritidis	O
+isolation	O
+frequency	O
+.	O
+
+In	O
+agreement	O
+with	O
+this	O
+southern	O
+blotting	O
+of	O
+mouse	O
+DNA	O
+with	O
+SmN	B-GENE
+probes	O
+reveals	O
+bands	O
+,	O
+additional	O
+to	O
+those	O
+derived	O
+from	O
+the	O
+pseudogene	O
+,	O
+which	O
+are	O
+characteristic	O
+of	O
+an	O
+intron	O
+-	O
+containing	O
+SmN	B-GENE
+gene	I-GENE
+.	O
+
+Two	O
+cDNAs	O
+encoding	O
+casein	B-GENE
+kinase	I-GENE
+-	I-GENE
+1	I-GENE
+have	O
+been	O
+isolated	O
+from	O
+a	O
+yeast	O
+cDNA	O
+library	O
+and	O
+termed	O
+CKI1	B-GENE
+and	O
+CKI2	B-GENE
+.	O
+
+Incidence	O
+rate	O
+ranging	O
+between	O
+122	O
+/	O
+100	O
+,	O
+000	O
+/	O
+year	O
+and	O
+190	O
+/	O
+100	O
+,	O
+000	O
+/	O
+year	O
+were	O
+found	O
+(	O
+minimum	O
+,	O
+estimated	O
+and	O
+raw	O
+datasets	O
+)	O
+.	O
+
+The	O
+observed	O
+sequence	O
+variation	O
+disrupts	O
+the	O
+first	O
+ORF	O
+in	O
+many	O
+Y	B-GENE
+'	O
+s	O
+while	O
+most	O
+of	O
+the	O
+second	O
+ORF	O
+including	O
+the	O
+putative	O
+helicase	B-GENE
+region	I-GENE
+is	O
+unaffected	O
+.	O
+
+The	O
+final	O
+screening	O
+yielded	O
+a	O
+clone	O
+containing	O
+a	O
+2	O
+kilobase	O
+(	O
+kb	O
+)	O
+insert	O
+.	O
+
+Lesions	O
+were	O
+made	O
+by	O
+pressure	O
+injection	O
+of	O
+kainic	O
+acid	O
+into	O
+the	O
+SOC	O
+through	O
+a	O
+stereotaxically	O
+positioned	O
+glass	O
+micropipette	O
+.	O
+
+A	O
+38	O
+-	O
+bp	O
+poly	O
+(	O
+dA	O
+-	O
+dT	O
+)	O
+region	O
+was	O
+found	O
+to	O
+be	O
+a	O
+positive	O
+regulator	O
+of	O
+Act1	B-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+We	O
+identified	O
+a	O
+protein	O
+,	O
+termed	O
+NFIL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+A	I-GENE
+(	O
+NF	B-GENE
+beta	I-GENE
+A	I-GENE
+)	O
+,	O
+that	O
+binds	O
+to	O
+a	O
+highly	O
+conserved	O
+12	O
+-	O
+bp	O
+DNA	O
+sequence	O
+(	O
+-	O
+49	O
+to	O
+-	O
+38	O
+)	O
+located	O
+upstream	O
+of	O
+the	O
+TATA	O
+box	O
+motif	O
+in	O
+both	O
+the	O
+human	B-GENE
+and	I-GENE
+murine	I-GENE
+IL	I-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+genes	I-GENE
+.	O
+
+We	O
+tried	O
+amphotericin	O
+B	O
+(	O
+AmB	O
+)	O
+,	O
+and	O
+remission	O
+of	O
+the	O
+tumor	O
+was	O
+obtained	O
+.	O
+
+Cutis	O
+aplasia	O
+.	O
+
+The	O
+DRF	B-GENE
+-	I-GENE
+2	I-GENE
+nuclear	I-GENE
+protein	I-GENE
+has	O
+characteristics	O
+similar	O
+to	O
+those	O
+of	O
+the	O
+muscle	O
+-	O
+specific	O
+regulatory	O
+factor	O
+,	O
+MEF	B-GENE
+-	I-GENE
+2	I-GENE
+(	O
+Buskin	O
+and	O
+Hauschka	O
+1989	O
+;	O
+Gossett	O
+et	O
+al	O
+.	O
+,	O
+1989	O
+)	O
+.	O
+
+From	O
+the	O
+15	O
+-	O
+kb	O
+clone	O
+a	O
+4	B-GENE
+-	I-GENE
+kb	I-GENE
+EcoRI	I-GENE
+fragment	I-GENE
+containing	O
+the	O
+first	O
+two	O
+exons	O
+and	O
+2	O
+.	O
+6	O
+kb	O
+of	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+opn	B-GENE
+gene	I-GENE
+was	O
+sequenced	O
+,	O
+and	O
+the	O
+transcriptional	O
+start	O
+site	O
+determined	O
+by	O
+primer	O
+extension	O
+analysis	O
+and	O
+S1	B-GENE
+nuclease	I-GENE
+mapping	O
+.	O
+
+Cardiovascular	O
+risk	O
+factors	O
+were	O
+measured	O
+by	O
+standardized	O
+techniques	O
+.	O
+
+Production	O
+costs	O
+included	O
+feed	O
+,	O
+non	O
+-	O
+feed	O
+operating	O
+,	O
+fixed	O
+,	O
+and	O
+replacement	O
+stock	O
+costs	O
+.	O
+
+We	O
+report	O
+a	O
+patient	O
+developing	O
+factor	B-GENE
+VII	I-GENE
+inhibitor	I-GENE
+possibly	O
+as	O
+a	O
+reaction	O
+to	O
+penicillin	O
+administration	O
+;	O
+it	O
+gave	O
+rise	O
+to	O
+fatal	O
+haemorrhage	O
+.	O
+
+Account	O
+was	O
+taken	O
+of	O
+noncellular	O
+and	O
+nonhuman	O
+elements	O
+in	O
+the	O
+smears	O
+;	O
+they	O
+included	O
+mucus	O
+,	O
+Charcot	O
+-	O
+Layden	O
+crystals	O
+,	O
+pollen	O
+grains	O
+,	O
+vegetal	O
+fragments	O
+and	O
+fungi	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+the	O
+carbon	O
+-	O
+perfused	O
+areas	O
+and	O
+MBF	O
+in	O
+the	O
+liver	O
+,	O
+renal	O
+cortex	O
+,	O
+spleen	O
+,	O
+and	O
+small	O
+intestinal	O
+serosa	O
+(	O
+only	O
+MBF	O
+)	O
+increased	O
+significantly	O
+5	O
+h	O
+after	O
+CLP	O
+.	O
+
+Lewis	O
+,	O
+N	O
+.	O
+
+This	O
+accurate	O
+and	O
+rapid	O
+method	O
+makes	O
+the	O
+MLPA	O
+test	O
+logistically	O
+feasible	O
+for	O
+large	O
+-	O
+scale	O
+screening	O
+.	O
+
+The	O
+modalities	O
+for	O
+using	O
+reference	O
+values	O
+for	O
+individual	O
+subjects	O
+as	O
+well	O
+as	O
+for	O
+groups	O
+are	O
+then	O
+discussed	O
+and	O
+the	O
+main	O
+points	O
+of	O
+research	O
+which	O
+must	O
+be	O
+faced	O
+in	O
+the	O
+near	O
+future	O
+regarding	O
+reference	O
+values	O
+are	O
+highlighted	O
+.	O
+
+The	O
+clinical	O
+application	O
+of	O
+the	O
+antibody	O
+-	O
+targeted	O
+Phthalocyanine	O
+was	O
+performed	O
+in	O
+3	O
+patients	O
+suffering	O
+from	O
+an	O
+advanced	O
+ovarian	O
+carcinoma	O
+(	O
+FIGO	O
+III	O
+)	O
+.	O
+
+We	O
+found	O
+that	O
+lung	O
+cancer	O
+tissues	O
+of	O
+positive	O
+67Ga	O
+scan	O
+expressed	O
+TFR	B-GENE
+,	O
+but	O
+those	O
+of	O
+a	O
+negative	O
+scan	O
+did	O
+not	O
+.	O
+
+This	O
+open	O
+reading	O
+frame	O
+was	O
+confirmed	O
+the	O
+correct	O
+one	O
+by	O
+direct	O
+amino	O
+-	O
+terminal	O
+sequence	O
+analysis	O
+of	O
+the	O
+overproduced	O
+msgB	B-GENE
+gene	I-GENE
+product	I-GENE
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+purified	O
+and	O
+characterized	O
+the	O
+recombinant	B-GENE
+furin	I-GENE
+from	O
+the	O
+conditioned	O
+medium	O
+of	O
+these	O
+cells	O
+.	O
+
+The	O
+virus	O
+encodes	O
+a	O
+40	O
+-	O
+kDa	O
+protein	O
+,	O
+tax	B-GENE
+,	O
+that	O
+is	O
+important	O
+for	O
+the	O
+immortalization	O
+of	O
+T	O
+cells	O
+.	O
+
+However	O
+,	O
+butyrate	O
+was	O
+at	O
+least	O
+2	O
+-	O
+fold	O
+more	O
+effective	O
+in	O
+stimulating	O
+CAT	B-GENE
+activity	O
+of	O
+fusion	O
+genes	O
+containing	O
+upstream	O
+sequences	O
+(	O
+-	O
+834	O
+to	O
+-	O
+576	O
+)	O
+than	O
+those	O
+containing	O
+proximal	O
+sequences	O
+(	O
+-	O
+456	O
+to	O
+-	O
+172	O
+)	O
+,	O
+suggesting	O
+two	O
+regions	O
+in	O
+the	O
+PSG1	B-GENE
+-	I-GENE
+I	I-GENE
+gene	I-GENE
+that	O
+mediate	O
+the	O
+butyrate	O
+response	O
+.	O
+
+An	O
+examination	O
+of	O
+the	O
+role	O
+of	O
+the	O
+carboxyl	O
+terminus	O
+in	O
+regulating	O
+NGFI	B-GENE
+-	I-GENE
+B	I-GENE
+transcriptional	O
+activity	O
+revealed	O
+that	O
+,	O
+in	O
+accordance	O
+with	O
+other	O
+nuclear	O
+receptors	O
+,	O
+mutants	O
+lacking	O
+portions	O
+of	O
+the	O
+carboxyl	O
+terminus	O
+had	O
+greatly	O
+decreased	O
+activity	O
+.	O
+
+Altogether	O
+these	O
+results	O
+indicate	O
+that	O
+the	O
+Syn	B-GENE
+5	I-GENE
+locus	I-GENE
+segregates	O
+from	O
+the	O
+gene	O
+specifying	O
+gH	B-GENE
+,	O
+to	O
+a	O
+region	O
+encompassing	O
+portions	O
+of	O
+the	O
+TK	B-GENE
+and	O
+UL	B-GENE
+24	I-GENE
+genes	I-GENE
+,	O
+and	O
+that	O
+the	O
+syn	B-GENE
+mutation	I-GENE
+does	O
+not	O
+affect	O
+the	O
+expression	O
+or	O
+activity	O
+of	O
+TK	B-GENE
+.	O
+
+Nucleoprotein	O
+(	O
+N	O
+)	O
+expressed	O
+by	O
+both	O
+recombinant	O
+vaccinia	O
+virus	O
+and	O
+TGEV	O
+had	O
+a	O
+relative	O
+molecular	O
+mass	O
+(	O
+Mr	O
+)	O
+of	O
+47	O
+,	O
+000	O
+and	O
+was	O
+susceptible	O
+to	O
+degradation	O
+at	O
+the	O
+C	O
+-	O
+terminus	O
+yielding	O
+discrete	O
+breakdown	O
+products	O
+.	O
+
+Recently	O
+,	O
+the	O
+3	B-GENE
+.	I-GENE
+6	I-GENE
+-	I-GENE
+kb	I-GENE
+full	I-GENE
+-	I-GENE
+length	I-GENE
+alpha	I-GENE
+-	I-GENE
+GalNAc	I-GENE
+cDNA	I-GENE
+sequence	I-GENE
+was	O
+isolated	O
+and	O
+found	O
+to	O
+have	O
+remarkable	O
+nucleotide	O
+and	O
+predicted	O
+amino	O
+acid	O
+homology	O
+(	O
+55	O
+.	O
+8	O
+and	O
+46	O
+.	O
+9	O
+%	O
+,	O
+respectively	O
+)	O
+with	O
+the	O
+human	B-GENE
+alpha	I-GENE
+-	I-GENE
+galactosidase	I-GENE
+A	I-GENE
+(	O
+alpha	B-GENE
+-	I-GENE
+Gal	I-GENE
+A	I-GENE
+)	O
+cDNA	O
+.	O
+
+The	O
+reason	O
+that	O
+nitrous	O
+oxide	O
+does	O
+not	O
+produce	O
+hydroxyl	O
+radicals	O
+readily	O
+might	O
+be	O
+that	O
+the	O
+one	O
+-	O
+electron	O
+reduction	O
+proceeds	O
+through	O
+an	O
+N2O	O
+-	O
+intermediate	O
+which	O
+is	O
+energetically	O
+very	O
+unfavourable	O
+:	O
+EO	O
+(	O
+N2O	O
+/	O
+N2O	O
+-	O
+)	O
+=	O
+-	O
+1	O
+.	O
+1	O
+V	O
+.	O
+
+All	O
+mutant	B-GENE
+JCV	I-GENE
+T	I-GENE
+antigens	I-GENE
+bound	O
+to	O
+JCV	O
+and	O
+SV40	O
+origins	O
+of	O
+DNA	O
+replication	O
+.	O
+
+Since	O
+each	O
+transcript	O
+appears	O
+to	O
+encode	O
+the	O
+same	O
+protein	O
+,	O
+this	O
+complexity	O
+may	O
+reflect	O
+the	O
+need	O
+for	O
+lineage	O
+-	O
+specific	O
+or	O
+differentiation	O
+-	O
+dependent	O
+control	O
+of	O
+expression	O
+.	O
+
+In	O
+patients	O
+with	O
+limited	O
+disease	O
+,	O
+the	O
+survival	O
+in	O
+the	O
+alternating	O
+arm	O
+was	O
+significantly	O
+superior	O
+to	O
+the	O
+survival	O
+in	O
+the	O
+CAV	O
+arm	O
+(	O
+P	O
+=	O
+.	O
+014	O
+)	O
+or	O
+the	O
+survival	O
+in	O
+the	O
+PE	O
+arm	O
+(	O
+P	O
+=	O
+.	O
+023	O
+)	O
+.	O
+
+We	O
+identify	O
+the	O
+"	O
+M	O
+region	O
+"	O
+of	O
+the	O
+muscle	B-GENE
+-	I-GENE
+specific	I-GENE
+Xenopus	I-GENE
+cardiac	I-GENE
+actin	I-GENE
+gene	I-GENE
+promoter	I-GENE
+from	O
+-	O
+282	O
+to	O
+-	O
+348	O
+as	O
+necessary	O
+for	O
+the	O
+embryonic	O
+expression	O
+of	O
+a	O
+cardiac	O
+actin	B-GENE
+-	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+reporter	O
+gene	O
+injected	O
+into	O
+fertilized	O
+eggs	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+previously	O
+identified	O
+and	O
+characterized	O
+attenuator	B-GENE
+1	I-GENE
+situated	O
+93	O
+nucleotides	O
+downstream	O
+from	O
+the	O
+major	O
+late	O
+transcription	O
+start	O
+site	O
+,	O
+a	O
+second	O
+attenuator	O
+,	O
+attenuator	B-GENE
+2	I-GENE
+,	O
+situated	O
+55	O
+nucleotides	O
+downstream	O
+from	O
+it	O
+,	O
+has	O
+been	O
+identified	O
+.	O
+
+EBNA	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+the	O
+cis	O
+-	O
+acting	O
+CD23	B-GENE
+element	I-GENE
+increased	O
+TK	B-GENE
+-	O
+promoted	O
+mRNA	O
+and	O
+did	O
+not	O
+alter	O
+the	O
+herpes	B-GENE
+simplex	I-GENE
+virus	I-GENE
+TK	I-GENE
+promoter	I-GENE
+transcription	I-GENE
+start	I-GENE
+site	I-GENE
+.	O
+
+These	O
+experiments	O
+delineate	O
+a	O
+186	O
+-	O
+bp	O
+,	O
+EBNA	B-GENE
+-	I-GENE
+2	I-GENE
+-	O
+responsive	O
+cell	O
+DNA	O
+fragment	O
+and	O
+provide	O
+firm	O
+evidence	O
+that	O
+EBNA	B-GENE
+-	I-GENE
+2	I-GENE
+transactivates	O
+transcription	O
+of	O
+cell	O
+genes	O
+.	O
+
+Plasma	O
+vitamin	O
+E	O
+,	O
+total	O
+lipids	O
+and	O
+myeloperoxidase	B-GENE
+levels	O
+during	O
+spinal	O
+surgery	O
+.	O
+
+Transfecting	O
+the	O
+cloned	O
+bovine	O
+PBR	B-GENE
+/	O
+IBP	B-GENE
+cDNA	O
+into	O
+COS	O
+-	O
+7	O
+cells	O
+resulted	O
+in	O
+an	O
+11	O
+-	O
+fold	O
+increase	O
+in	O
+the	O
+density	O
+of	O
+high	O
+affinity	O
+[	O
+3H	O
+]	O
+PK	O
+11195	O
+binding	O
+sites	O
+which	O
+had	O
+only	O
+low	O
+affinity	O
+for	O
+Ro5	O
+-	O
+4864	O
+.	O
+
+The	O
+initial	O
+phase	O
+of	O
+increased	O
+vascular	O
+permeability	O
+in	O
+the	O
+peritoneal	O
+cavity	O
+and	O
+LTB4	O
+production	O
+was	O
+dose	O
+dependently	O
+inhibited	O
+by	O
+the	O
+5	O
+-	O
+LO	O
+inhibitors	O
+phenidone	O
+,	O
+BW	O
+A4C	O
+,	O
+A63162	O
+,	O
+and	O
+ICI	O
+207	O
+968	O
+but	O
+not	O
+by	O
+dexamethasone	O
+or	O
+colchicine	O
+.	O
+
+Discrepant	O
+results	O
+with	O
+a	O
+latex	O
+agglutination	O
+test	O
+in	O
+the	O
+assessment	O
+of	O
+cytomegalovirus	O
+antibody	O
+status	O
+of	O
+cardiac	O
+transplant	O
+donors	O
+.	O
+
+Each	O
+mRNA	O
+contained	O
+five	O
+or	O
+six	O
+internal	O
+uridine	O
+residues	O
+,	O
+which	O
+were	O
+transcribed	O
+using	O
+a	O
+mixture	O
+of	O
+UTP	O
+and	O
+thio	O
+-	O
+UTP	O
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+sequenced	O
+two	O
+overlapping	O
+cDNA	O
+fragments	O
+which	O
+could	O
+encode	O
+the	O
+complete	O
+amino	O
+acid	O
+sequence	O
+of	O
+rat	B-GENE
+testis	I-GENE
+fructose	I-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+phosphate	I-GENE
+,	I-GENE
+2	I-GENE
+-	I-GENE
+kinase	I-GENE
+:	O
+fructose	B-GENE
+-	I-GENE
+2	I-GENE
+,	I-GENE
+6	I-GENE
+-	I-GENE
+bisphosphatase	I-GENE
+.	O
+
+We	O
+have	O
+identified	O
+SWI5	B-GENE
+'	O
+s	O
+nuclear	O
+localization	O
+signal	O
+(	O
+NLS	O
+)	O
+and	O
+show	O
+that	O
+it	O
+can	O
+confer	O
+cell	O
+cycle	O
+-	O
+dependent	O
+nuclear	O
+entry	O
+to	O
+a	O
+heterologous	O
+protein	O
+.	O
+
+In	O
+contrast	O
+to	O
+behavioral	O
+deviation	O
+(	O
+the	O
+avoidance	O
+conditioning	O
+lost	O
+)	O
+,	O
+the	O
+haloperidol	O
+intrastriatal	O
+microinjections	O
+did	O
+not	O
+affect	O
+the	O
+DA	O
+synaptic	O
+level	O
+in	O
+rostral	O
+neostriatum	O
+.	O
+
+In	O
+similar	O
+transient	O
+transfection	O
+experiments	O
+in	O
+HeLa	O
+cells	O
+,	O
+overexpression	O
+of	O
+the	O
+wt	B-GENE
+human	I-GENE
+retinoblastoma	I-GENE
+susceptibility	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+RB	B-GENE
+,	O
+was	O
+found	O
+to	O
+repress	O
+the	O
+serum	O
+-	O
+induced	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+-	O
+225	O
+to	O
++	O
+13	O
+)	O
+,	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+(	O
+-	O
+711	O
+to	O
++	O
+42	O
+)	O
+,	O
+and	O
+beta	B-GENE
+-	I-GENE
+actin	I-GENE
+(	O
+-	O
+3400	O
+to	O
++	O
+912	O
+)	O
+promoters	O
+but	O
+not	O
+the	O
+PRV	O
+-	O
+induced	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+-	O
+110	O
+to	O
++	O
+13	O
+)	O
+or	O
+the	O
+serum	O
+-	O
+induced	O
+MHC	B-GENE
+(	O
+-	O
+528	O
+to	O
+-	O
+38	O
+)	O
+promoters	O
+.	O
+
+This	O
+repression	O
+was	O
+mediated	O
+through	O
+binding	O
+to	O
+the	O
+E2	B-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+immediately	O
+upstream	O
+of	O
+the	O
+P105	B-GENE
+promoter	O
+TATA	O
+box	O
+and	O
+could	O
+be	O
+abrogated	O
+by	O
+preincubation	O
+of	O
+the	O
+HPV	B-GENE
+-	I-GENE
+18	I-GENE
+P105	I-GENE
+promoter	I-GENE
+template	O
+with	O
+the	O
+nuclear	O
+extract	O
+allowing	O
+the	O
+formation	O
+of	O
+the	O
+preinitiation	O
+complex	O
+.	O
+
+We	O
+did	O
+not	O
+detect	O
+p50	B-GENE
+in	O
+association	O
+with	O
+native	B-GENE
+glucocorticoid	I-GENE
+receptor	I-GENE
+in	O
+L	O
+cells	O
+or	O
+with	O
+the	O
+overexpressed	O
+glucocorticoid	B-GENE
+receptor	I-GENE
+in	O
+Chinese	O
+hamster	O
+ovary	O
+cells	O
+.	O
+
+Two	O
+putative	O
+12	O
+-	O
+O	O
+-	O
+tetradecanoyl	O
+-	O
+phorbol	O
+-	O
+13	O
+-	O
+acetate	O
+(	O
+TPA	O
+)	O
+response	O
+elements	O
+,	O
+that	O
+might	O
+serve	O
+as	O
+binding	O
+sites	O
+for	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+AP	I-GENE
+-	I-GENE
+1	I-GENE
+and	O
+a	O
+consensus	O
+sequence	O
+of	O
+a	O
+transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+beta	I-GENE
+1	I-GENE
+(	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+1	I-GENE
+)	O
+inhibitory	O
+element	O
+were	O
+found	O
+in	O
+the	O
+promoter	O
+region	O
+.	O
+
+TPA	O
+and	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+1	I-GENE
+did	O
+not	O
+markedly	O
+affect	O
+the	O
+activities	O
+of	O
+the	O
+72	O
+-	O
+kDa	O
+enzyme	O
+.	O
+
+They	O
+were	O
+almost	O
+regularly	O
+excited	O
+by	O
+pressure	O
+to	O
+the	O
+ipsilateral	O
+cornea	O
+or	O
+to	O
+both	O
+corneas	O
+at	O
+a	O
+strength	O
+well	O
+above	O
+the	O
+human	O
+corneal	O
+pain	O
+threshold	O
+.	O
+
+Feed	O
+intake	O
+was	O
+not	O
+affected	O
+by	O
+dietary	O
+KCl	O
+or	O
+NaHCO3	O
+supplementation	O
+,	O
+but	O
+average	O
+daily	O
+gain	O
+increased	O
+with	O
+increased	O
+K	O
+and	O
+tended	O
+to	O
+be	O
+reduced	O
+by	O
+dietary	O
+NaHCO3	O
+.	O
+
+Extraction	O
+procedure	O
+for	O
+the	O
+measurement	O
+of	O
+butyltin	O
+compounds	O
+in	O
+biological	O
+tissues	O
+using	O
+toluene	O
+,	O
+HBr	O
+,	O
+and	O
+tropolone	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+have	O
+cloned	O
+a	O
+region	O
+that	O
+complements	O
+the	O
+exoenzyme	B-GENE
+S	I-GENE
+-	O
+deficient	O
+phenotype	O
+of	O
+strain	O
+388	O
+exs1	B-GENE
+:	O
+:	O
+Tn1	B-GENE
+,	O
+a	O
+chromosomal	B-GENE
+Tn1	I-GENE
+insertional	I-GENE
+mutation	I-GENE
+.	O
+
+Alignment	O
+of	O
+the	O
+amino	O
+acid	O
+sequences	O
+surrounding	O
+Tyr	O
+-	O
+766	O
+with	O
+corresponding	O
+regions	O
+of	O
+other	O
+FGFRs	B-GENE
+revealed	O
+conserved	O
+tyrosine	O
+residues	O
+in	O
+all	O
+known	O
+members	O
+of	O
+the	O
+FGFR	B-GENE
+family	I-GENE
+.	O
+
+The	O
+transcription	O
+initiation	O
+site	O
+was	O
+determined	O
+to	O
+occur	O
+66	O
+bp	O
+upstream	O
+of	O
+the	O
+initiating	O
+Met	O
+.	O
+
+All	O
+anti	B-GENE
+-	I-GENE
+I	I-GENE
+and	O
+anti	B-GENE
+-	I-GENE
+i	I-GENE
+CA	I-GENE
+were	O
+shown	O
+to	O
+express	O
+VH4	B-GENE
+heavy	I-GENE
+chains	I-GENE
+,	O
+and	O
+14	O
+of	O
+17	O
+CA	B-GENE
+expressed	O
+a	O
+previously	O
+described	O
+VH4	B-GENE
+second	O
+hypervariable	O
+region	O
+determinant	O
+,	O
+termed	O
+VH4	B-GENE
+-	I-GENE
+HV2a	I-GENE
+.	O
+
+Intron	O
+K1	B-GENE
+cox1	I-GENE
+.	I-GENE
+2	I-GENE
+is	O
+not	O
+found	O
+in	O
+S	O
+.	O
+cerevisiae	O
+and	O
+appears	O
+at	O
+an	O
+unique	O
+location	O
+in	O
+K	O
+.	O
+lactis	O
+.	O
+
+We	O
+have	O
+determined	O
+that	O
+the	O
+mutants	O
+define	O
+two	O
+complementation	O
+groups	O
+,	O
+designated	O
+cgs1	B-GENE
++	I-GENE
+and	O
+cgs2	B-GENE
++	I-GENE
+(	O
+continues	O
+to	O
+grow	O
+in	O
+stationary	O
+)	O
+.	O
+
+The	O
+results	O
+of	O
+induced	O
+coexpression	O
+were	O
+also	O
+supported	O
+by	O
+rapid	O
+generation	O
+of	O
+FeLV	O
+recombinants	O
+when	O
+FeLV	O
+-	O
+C	O
+was	O
+used	O
+to	O
+infect	O
+the	O
+feline	O
+3201B	O
+cell	O
+line	O
+that	O
+constitutively	O
+expresses	O
+high	O
+levels	O
+of	O
+endogenous	O
+FeLV	O
+-	O
+specific	O
+mRNAs	O
+.	O
+
+Recombination	O
+between	O
+feline	O
+leukemia	O
+virus	O
+subgroup	O
+B	O
+or	O
+C	O
+and	O
+endogenous	O
+env	B-GENE
+elements	O
+alters	O
+the	O
+in	O
+vitro	O
+biological	O
+activities	O
+of	O
+the	O
+viruses	O
+.	O
+
+The	O
+nucleotide	O
+sequences	O
+at	O
+the	O
+5	O
+'	O
+and	O
+3	O
+'	O
+ends	O
+of	O
+these	O
+introns	O
+are	O
+characteristic	O
+of	O
+spliced	O
+transcripts	O
+from	O
+eukaryotic	O
+protein	O
+-	O
+encoding	O
+genes	O
+,	O
+with	O
+one	O
+significant	O
+difference	O
+;	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+LAT	B-GENE
+intron	I-GENE
+is	O
+GC	O
+instead	O
+of	O
+the	O
+consensus	O
+sequence	O
+GT	O
+.	O
+
+At	O
+1	O
+,	O
+5	O
+,	O
+and	O
+9	O
+months	O
+after	O
+initial	O
+isolation	O
+of	O
+C	O
+.	O
+kutscheri	O
+from	O
+the	O
+oral	O
+cavity	O
+,	O
+hamsters	O
+were	O
+euthanatized	O
+,	O
+and	O
+attempts	O
+were	O
+made	O
+to	O
+culture	O
+C	O
+.	O
+kutscheri	O
+from	O
+13	O
+additional	O
+sites	O
+.	O
+
+The	O
+strategy	O
+has	O
+been	O
+used	O
+to	O
+determine	O
+2	O
+.	O
+6	O
+kilobases	O
+of	O
+nucleotide	O
+sequence	O
+in	O
+the	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+ADE	I-GENE
+1	I-GENE
+locus	I-GENE
+.	O
+
+Two	O
+independent	O
+promoters	O
+as	O
+well	O
+as	O
+5	O
+'	O
+untranslated	O
+regions	O
+regulate	O
+Dd	B-GENE
+ras	I-GENE
+expression	O
+in	O
+Dictyostelium	O
+.	O
+
+The	O
+results	O
+suggested	O
+that	O
+,	O
+depending	O
+upon	O
+the	O
+cell	O
+type	O
+,	O
+gene	O
+cotransfer	O
+using	O
+aminoglycoside	O
+resistance	O
+as	O
+a	O
+selectable	O
+marker	O
+may	O
+seriously	O
+perturb	O
+important	O
+cellular	O
+control	O
+mechanisms	O
+such	O
+as	O
+the	O
+PKC	B-GENE
+pathway	O
+leading	O
+to	O
+activation	O
+of	O
+gene	O
+expression	O
+.	O
+
+Therefore	O
+,	O
+the	O
+strD	B-GENE
+and	O
+strE	B-GENE
+genes	I-GENE
+could	O
+serve	O
+as	O
+universal	O
+probes	O
+indicative	O
+of	O
+the	O
+presence	O
+of	O
+biosynthetic	O
+capacity	O
+for	O
+6	O
+-	O
+deoxyhexose	O
+moieties	O
+.	O
+
+The	O
+two	O
+genes	O
+code	O
+for	O
+polypeptides	B-GENE
+of	I-GENE
+420	I-GENE
+amino	I-GENE
+acids	I-GENE
+(	I-GENE
+M	I-GENE
+.	I-GENE
+HgiCI	I-GENE
+)	I-GENE
+and	O
+345	B-GENE
+amino	I-GENE
+acids	I-GENE
+(	I-GENE
+R	I-GENE
+.	I-GENE
+HgiCI	I-GENE
+)	I-GENE
+.	O
+
+Expression	O
+of	O
+the	O
+wt1	B-GENE
+gene	I-GENE
+via	O
+transient	O
+transfection	O
+in	O
+COS	O
+-	O
+1	O
+cells	O
+revealed	O
+a	O
+52	O
+kDa	O
+protein	O
+which	O
+was	O
+immunoprecipitated	O
+by	O
+both	O
+the	O
+N	O
+-	O
+terminal	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+-	O
+specific	O
+antisera	O
+.	O
+
+The	O
+factor	O
+which	O
+binds	O
+to	O
+the	O
+TR	B-GENE
+promoter	I-GENE
+co	O
+-	O
+sedimented	O
+with	O
+SV40	O
+chromosomes	O
+extracted	O
+late	O
+in	O
+infection	O
+.	O
+
+Temafloxacin	O
+400	O
+mg	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+administered	O
+orally	O
+for	O
+28	O
+days	O
+represents	O
+a	O
+safe	O
+and	O
+effective	O
+treatment	O
+for	O
+chronic	O
+bacterial	O
+prostatitis	O
+.	O
+
+Its	O
+neuromuscular	O
+effects	O
+are	O
+similar	O
+to	O
+a	O
+single	O
+ED90	O
+dose	O
+of	O
+vecuronium	O
+.	O
+
+The	O
+patient	O
+with	O
+a	O
+prolonged	O
+fever	O
+caused	O
+by	O
+dissecting	O
+aneurysm	O
+of	O
+the	O
+aorta	O
+in	O
+whom	O
+pleuropneumonia	O
+masked	O
+the	O
+real	O
+diseases	O
+has	O
+been	O
+presented	O
+.	O
+
+The	O
+resulting	O
+clone	O
+pKB11	B-GENE
+,	O
+which	O
+has	O
+a	O
+1369	O
+-	O
+base	O
+pair	O
+(	O
+bp	O
+)	O
+cDNA	O
+insert	O
+,	O
+overlapping	O
+pCAD142	B-GENE
+by	O
+781	O
+bp	O
+,	O
+was	O
+identified	O
+by	O
+hybridization	O
+methods	O
+and	O
+sequence	O
+analysis	O
+and	O
+found	O
+to	O
+contain	O
+the	O
+entire	O
+cDNA	O
+sequence	O
+for	O
+the	O
+amino	O
+end	O
+of	O
+the	O
+CAD	B-GENE
+polypeptide	I-GENE
+.	O
+
+This	O
+conclusion	O
+was	O
+confirmed	O
+by	O
+Northern	O
+blotting	O
+analysis	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+CAD	B-GENE
+gene	I-GENE
+.	O
+
+We	O
+report	O
+the	O
+isolation	O
+of	O
+genomic	O
+and	O
+cDNA	O
+clones	O
+of	O
+the	O
+light	O
+-	O
+independent	O
+Sn	B-GENE
+:	I-GENE
+bol3	I-GENE
+allele	I-GENE
+.	O
+
+Its	O
+clearance	O
+has	O
+been	O
+found	O
+to	O
+be	O
+decreased	O
+(	O
+typically	O
+by	O
+around	O
+25	O
+%	O
+,	O
+but	O
+often	O
+by	O
+far	O
+more	O
+)	O
+by	O
+erythromycin	O
+,	O
+troleandomycin	O
+(	O
+triacetyloleandomycin	O
+)	O
+,	O
+roxithromycin	O
+,	O
+enoxacin	O
+,	O
+ciprofloxacin	O
+,	O
+pefloxacin	O
+,	O
+norfloxacin	O
+,	O
+ofloxacin	O
+,	O
+fluoroquinolone	O
+T	O
+-	O
+3262	O
+,	O
+pipemidic	O
+acid	O
+,	O
+cimetidine	O
+,	O
+etintidine	O
+,	O
+propranolol	O
+,	O
+verapamil	O
+,	O
+diltiazem	O
+,	O
+nifedipine	O
+,	O
+furosemide	O
+(	O
+frusemide	O
+)	O
+,	O
+at	O
+least	O
+some	O
+anovulent	O
+agents	O
+,	O
+viloxazine	O
+,	O
+allopurinol	O
+,	O
+ticlopidine	O
+,	O
+idrocilamide	O
+,	O
+thiabendazole	O
+,	O
+disulfiram	O
+,	O
+influenza	O
+-	O
+and	O
+BCG	O
+-	O
+vaccination	O
+,	O
+interferon	B-GENE
+,	O
+and	O
+caffeine	O
+(	O
+half	O
+-	O
+life	O
+increase	O
+)	O
+.	O
+
+We	O
+enrolled	O
+253	O
+HIV	B-GENE
+-	I-GENE
+antibody	I-GENE
+positive	O
+heroin	O
+addicts	O
+without	O
+HIV	O
+-	O
+related	O
+disease	O
+(	O
+n	O
+=	O
+81	O
+)	O
+or	O
+with	O
+persistent	O
+generalized	O
+lymphadenopathy	O
+(	O
+n	O
+=	O
+172	O
+)	O
+in	O
+a	O
+prospective	O
+study	O
+to	O
+evaluate	O
+clinical	O
+progression	O
+to	O
+AIDS	O
+related	O
+complex	O
+(	O
+ARC	O
+)	O
+or	O
+AIDS	O
+and	O
+to	O
+identify	O
+factors	O
+of	O
+possible	O
+prognostic	O
+relevance	O
+.	O
+
+No	O
+homology	O
+was	O
+found	O
+between	O
+RNA14	B-GENE
+and	O
+RNA15	B-GENE
+or	O
+between	O
+RNA14	B-GENE
+and	O
+other	O
+proteins	O
+contained	O
+in	O
+data	O
+banks	O
+.	O
+
+Mutations	O
+in	O
+the	O
+yeast	B-GENE
+RNA14	I-GENE
+and	O
+RNA15	B-GENE
+genes	I-GENE
+result	O
+in	O
+an	O
+abnormal	O
+mRNA	O
+decay	O
+rate	O
+;	O
+sequence	O
+analysis	O
+reveals	O
+an	O
+RNA	O
+-	O
+binding	O
+domain	O
+in	O
+the	O
+RNA15	B-GENE
+protein	I-GENE
+.	O
+
+Myocardial	O
+infarction	O
+in	O
+patients	O
+with	O
+previous	O
+bypass	O
+surgery	O
+.	O
+
+The	O
+most	O
+striking	O
+difference	O
+in	O
+the	O
+birch	B-GENE
+NAD	I-GENE
+(	I-GENE
+P	I-GENE
+)	I-GENE
+H	I-GENE
+-	I-GENE
+NR	I-GENE
+sequence	I-GENE
+in	O
+comparison	O
+to	O
+NADH	B-GENE
+-	I-GENE
+NR	I-GENE
+sequences	I-GENE
+was	O
+found	O
+at	O
+the	O
+putative	O
+pyridine	O
+nucleotide	O
+binding	O
+site	O
+.	O
+
+A	O
+single	O
+amino	O
+acid	O
+difference	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+influences	O
+dominant	O
+negative	O
+activity	O
+and	O
+receptor	O
+dimer	O
+formation	O
+.	O
+
+The	O
+95	O
+%	O
+confidence	O
+values	O
+(	O
+2SD	O
+)	O
+for	O
+the	O
+change	O
+in	O
+Ros	O
+required	O
+to	O
+exclude	O
+natural	O
+variability	O
+were	O
+0	O
+.	O
+39	O
+,	O
+0	O
+.	O
+50	O
+and	O
+0	O
+.	O
+53	O
+cmH2O	O
+l	O
+-	O
+1	O
+s	O
+,	O
+respectively	O
+.	O
+
+Among	O
+953	O
+infants	O
+in	O
+22	O
+neonatal	O
+care	O
+units	O
+studied	O
+,	O
+23	O
+%	O
+(	O
+median	O
+value	O
+,	O
+range	O
+0	O
+-	O
+78	O
+)	O
+were	O
+found	O
+to	O
+be	O
+faecally	O
+colonized	O
+with	O
+one	O
+of	O
+21	O
+distinct	O
+nosocomial	O
+strains	O
+of	O
+Escherichia	O
+coli	O
+,	O
+Klebsiella	O
+or	O
+Enterobacter	O
+spp	O
+.	O
+
+Biochemical	O
+studies	O
+revealed	O
+the	O
+expected	O
+loss	O
+of	O
+ChAT	B-GENE
+activity	O
+in	O
+the	O
+dorsal	O
+and	O
+ventral	O
+hippocampi	O
+of	O
+lesioned	O
+animals	O
+along	O
+with	O
+elevated	O
+levels	O
+of	O
+norepinephrine	O
+(	O
+NE	O
+)	O
+in	O
+the	O
+dorsal	O
+hippocampus	O
+of	O
+MS	O
+/	O
+HSI	O
+animals	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+The	O
+localization	O
+of	O
+this	O
+proteoglycan	O
+locus	O
+in	O
+the	O
+human	O
+genome	O
+and	O
+the	O
+availability	O
+of	O
+new	O
+RFLPs	O
+provide	O
+the	O
+tools	O
+for	O
+future	O
+studies	O
+of	O
+human	O
+diseases	O
+where	O
+the	O
+HSPG2	B-GENE
+proteoglycan	I-GENE
+gene	I-GENE
+is	O
+suspected	O
+to	O
+be	O
+involved	O
+.	O
+
+After	O
+2	O
+min	O
+of	O
+dobutamine	O
+injection	O
+,	O
+or	O
+after	O
+20	O
+min	O
+of	O
+pimobendan	O
+injection	O
+,	O
+the	O
+myocardium	O
+was	O
+removed	O
+,	O
+and	O
+used	O
+for	O
+determination	O
+of	O
+the	O
+tissue	O
+levels	O
+of	O
+metabolites	O
+of	O
+energy	O
+and	O
+carbohydrate	O
+metabolism	O
+.	O
+
+During	O
+coronary	O
+stenosis	O
+,	O
+on	O
+the	O
+contrary	O
+,	O
+intracoronary	O
+procaterol	O
+at	O
+the	O
+same	O
+dose	O
+significantly	O
+deteriorated	O
+regional	O
+myocardial	O
+dysfunction	O
+without	O
+changing	O
+LCX	O
+flow	O
+,	O
+global	O
+hemodynamics	O
+and	O
+cardiac	O
+lactate	O
+metabolism	O
+.	O
+
+Here	O
+we	O
+present	O
+evidence	O
+that	O
+major	B-GENE
+IE	I-GENE
+proteins	I-GENE
+IE86	B-GENE
+,	O
+IE72	B-GENE
+,	O
+and	O
+IE55	B-GENE
+are	O
+capable	O
+of	O
+trans	O
+-	O
+activating	O
+the	O
+HIV	B-GENE
+LTR	I-GENE
+in	O
+a	O
+T	O
+-	O
+cell	O
+line	O
+,	O
+HUT	O
+-	O
+78	O
+.	O
+
+In	O
+a	O
+country	O
+where	O
+general	O
+HIV	O
+prevalence	O
+is	O
+low	O
+,	O
+the	O
+strategy	O
+is	O
+cost	O
+-	O
+effective	O
+for	O
+location	O
+and	O
+counselling	O
+of	O
+unknowingly	O
+seropositive	O
+individuals	O
+.	O
+
+The	O
+cis	O
+-	O
+acting	O
+element	O
+mediating	O
+glucocorticoid	O
+inducibility	O
+of	O
+the	O
+chicken	B-GENE
+glutamine	I-GENE
+synthetase	I-GENE
+gene	I-GENE
+has	O
+been	O
+identified	O
+.	O
+
+However	O
+,	O
+the	O
+increase	O
+in	O
+biliary	O
+excretion	O
+did	O
+not	O
+compensate	O
+for	O
+the	O
+reduced	O
+elimination	O
+of	O
+bretylium	O
+and	O
+hexylsalicylic	O
+acid	O
+via	O
+the	O
+kidney	O
+.	O
+
+Diagnostic	O
+value	O
+of	O
+cerebrospinal	B-GENE
+fluid	I-GENE
+immunoglobulin	I-GENE
+G	I-GENE
+(	O
+IgG	B-GENE
+)	O
+in	O
+pediatric	O
+neurological	O
+diseases	O
+.	O
+
+Expression	O
+of	O
+six	O
+genes	O
+,	O
+ipaB	B-GENE
+,	O
+ipaC	B-GENE
+,	O
+invE	B-GENE
+,	O
+invG	B-GENE
+,	O
+invJ	B-GENE
+,	O
+and	O
+invK	B-GENE
+,	O
+was	O
+apparently	O
+regulated	O
+by	O
+the	O
+positive	O
+regulator	O
+virF	B-GENE
+.	O
+
+Inducible	O
+VT	O
+was	O
+suppressed	O
+entirely	O
+in	O
+one	O
+patient	O
+.	O
+
+The	O
+presence	O
+of	O
+the	O
+corresponding	O
+mature	O
+mRNA	O
+transcripts	O
+(	O
+3	O
+.	O
+2	O
+-	O
+3	O
+.	O
+5	O
+kilobase	O
+pairs	O
+(	O
+kb	O
+]	O
+in	O
+human	O
+fibroblasts	O
+was	O
+shown	O
+by	O
+Northern	O
+blot	O
+hybridization	O
+,	O
+S1	B-GENE
+nuclease	I-GENE
+protection	O
+assay	O
+,	O
+and	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+.	O
+
+Approximately	O
+50	O
+%	O
+of	O
+the	O
+ribosomal	O
+DNA	O
+(	O
+rDNA	O
+)	O
+units	O
+of	O
+Drosophila	O
+melanogaster	O
+are	O
+inactivated	O
+by	O
+two	O
+different	O
+28	B-GENE
+S	I-GENE
+RNA	I-GENE
+ribosomal	I-GENE
+gene	I-GENE
+insertions	O
+(	O
+type	O
+I	O
+and	O
+type	O
+II	O
+)	O
+.	O
+
+Gap	B-GENE
+b3	I-GENE
+consists	O
+of	O
+two	O
+polypeptide	O
+chains	O
+(	O
+Mr	O
+=	O
+110	O
+,	O
+000	O
+and	O
+30	O
+,	O
+000	O
+)	O
+,	O
+which	O
+seem	O
+to	O
+be	O
+proteolytic	O
+cleavage	O
+products	O
+connected	O
+by	O
+disulfide	O
+bonds	O
+from	O
+a	O
+precursor	O
+protein	O
+.	O
+
+However	O
+,	O
+the	O
+rtFc	B-GENE
+gamma	I-GENE
+R	I-GENE
+alpha	I-GENE
+cDNA	I-GENE
+clone	O
+is	O
+complementary	O
+to	O
+at	O
+least	O
+two	O
+different	O
+-	O
+sized	O
+mRNAs	O
+expressed	O
+by	O
+CRNK	O
+-	O
+16	O
+cells	O
+,	O
+contrasting	O
+the	O
+single	O
+Fc	B-GENE
+gamma	I-GENE
+R	I-GENE
+-	I-GENE
+related	I-GENE
+mRNA	I-GENE
+species	O
+expressed	O
+by	O
+human	O
+and	O
+mouse	O
+natural	O
+killer	O
+cells	O
+.	O
+
+Both	O
+genes	O
+comprise	O
+three	O
+exons	O
+,	O
+two	O
+introns	O
+and	O
+an	O
+unusually	O
+long	O
+3	O
+'	O
+-	O
+untranslated	O
+region	O
+(	O
+3	O
+.	O
+2	O
+kilobase	O
+pairs	O
+)	O
+,	O
+specificying	O
+a	O
+mRNA	O
+of	O
+approximately	O
+4	O
+.	O
+1	O
+kilobases	O
+.	O
+
+This	O
+exon	O
+,	O
+here	O
+named	O
+exon	O
+0	O
+,	O
+contained	O
+the	O
+entire	O
+5	O
+'	O
+untranslated	O
+region	O
+and	O
+the	O
+N	O
+-	O
+terminal	O
+signal	O
+sequence	O
+of	O
+the	O
+polypeptide	O
+.	O
+
+Treatment	O
+of	O
+human	O
+myeloid	O
+cell	O
+lines	O
+HL	O
+-	O
+60	O
+and	O
+U937	O
+with	O
+phorbol	O
+12	O
+-	O
+myristate	O
+13	O
+-	O
+acetate	O
+(	O
+PMA	O
+)	O
+increased	O
+within	O
+2	O
+h	O
+cellular	O
+levels	O
+of	O
+the	O
+RNA	O
+hybridizable	O
+to	O
+LD78	B-GENE
+cDNA	I-GENE
+.	O
+
+A	O
+new	O
+,	O
+flexible	O
+fiberoptic	O
+ventriculoscope	O
+for	O
+observation	O
+of	O
+the	O
+ventricles	O
+and	O
+major	O
+cisterns	O
+is	O
+reported	O
+.	O
+
+Isopenicillin	B-GENE
+N	I-GENE
+isomerase	I-GENE
+(	O
+epimerase	B-GENE
+)	O
+has	O
+been	O
+purified	O
+from	O
+Streptomyces	O
+clavuligerus	O
+,	O
+and	O
+the	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+N	O
+-	O
+terminus	O
+has	O
+been	O
+determined	O
+.	O
+
+Serum	O
+IgG	B-GENE
+was	O
+initially	O
+elevated	O
+in	O
+6	O
+patients	O
+.	O
+
+The	O
+patient	O
+initially	O
+attained	O
+complete	O
+remission	O
+(	O
+CR1	O
+)	O
+with	O
+conventional	O
+chemotherapy	O
+and	O
+then	O
+relapsed	O
+14	O
+months	O
+later	O
+.	O
+
+157	O
++	O
+/	O
+-	O
+16	O
+mg	O
+/	O
+dl	O
+;	O
+NS	O
+)	O
+,	O
+glucose	O
+levels	O
+,	O
+and	O
+basal	O
+(	O
+17	O
++	O
+/	O
+-	O
+4	O
+vs	O
+.	O
+
+Platelet	O
+aggregation	O
+and	O
+metabolic	O
+control	O
+are	O
+not	O
+affected	O
+by	O
+calcium	O
+antagonist	O
+treatment	O
+in	O
+type	O
+II	O
+diabetes	O
+mellitus	O
+.	O
+
+Wnt	B-GENE
+-	I-GENE
+1	I-GENE
+(	O
+int	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+is	O
+a	O
+cellular	O
+oncogene	O
+often	O
+activated	O
+by	O
+insertion	O
+of	O
+proviral	O
+DNA	O
+of	O
+the	O
+mouse	O
+mammary	O
+tumor	O
+virus	O
+.	O
+
+Induction	O
+of	O
+Jurkat	O
+leukemic	O
+T	O
+cells	O
+with	O
+phorbol	O
+12	O
+-	O
+myristate	O
+13	O
+-	O
+acetate	O
+and	O
+ionomycin	O
+did	O
+not	O
+affect	O
+the	O
+level	O
+of	O
+FKBP	B-GENE
+mRNA	I-GENE
+.	O
+
+GLUT5	B-GENE
+mRNA	I-GENE
+is	O
+expressed	O
+at	O
+highest	O
+levels	O
+in	O
+small	O
+intestine	O
+and	O
+at	O
+much	O
+lower	O
+levels	O
+in	O
+kidney	O
+,	O
+skeletal	O
+muscle	O
+,	O
+and	O
+adipose	O
+tissue	O
+.	O
+
+e	O
+.	O
+
+We	O
+speculate	O
+that	O
+these	O
+tumors	O
+may	O
+represent	O
+congenital	O
+hamartomatous	O
+growths	O
+.	O
+
+Identification	O
+and	O
+characterization	O
+of	O
+the	O
+promoter	O
+for	O
+the	O
+cytotactin	B-GENE
+gene	I-GENE
+.	O
+
+(	O
+1988	O
+)	O
+J	O
+.	O
+
+These	O
+results	O
+strongly	O
+suggested	O
+that	O
+similar	O
+,	O
+if	O
+not	O
+identical	O
+,	O
+the	O
+CArG	B-GENE
+box	I-GENE
+binding	I-GENE
+proteins	I-GENE
+interact	O
+with	O
+the	O
+functionally	O
+different	O
+promoter	O
+element	O
+in	O
+the	O
+VLC1	B-GENE
+,	O
+cardiac	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+,	O
+and	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+genes	I-GENE
+.	O
+
+Polyadenylation	O
+of	O
+B4	B-GENE
+RNA	I-GENE
+,	O
+which	O
+occurs	O
+very	O
+early	O
+during	O
+maturation	O
+,	O
+is	O
+limited	O
+to	O
+150	O
+residues	O
+,	O
+and	O
+it	O
+is	O
+this	O
+number	O
+that	O
+is	O
+required	O
+for	O
+polysomal	O
+recruitment	O
+.	O
+
+Co	O
+-	O
+existence	O
+of	O
+these	O
+regulatory	O
+elements	O
+with	O
+other	O
+elements	O
+,	O
+such	O
+as	O
+the	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+element	I-GENE
+or	O
+CCAAT	O
+box	O
+,	O
+was	O
+also	O
+found	O
+.	O
+
+Recently	O
+,	O
+studies	O
+of	O
+agents	O
+that	O
+disrupt	O
+collagen	B-GENE
+synthesis	O
+and	O
+deposition	O
+have	O
+yielded	O
+several	O
+new	O
+angiogenesis	O
+inhibitors	O
+.	O
+
+Since	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+this	O
+gene	O
+is	O
+likely	O
+involved	O
+in	O
+hormonal	O
+regulation	O
+of	O
+its	O
+expression	O
+,	O
+we	O
+have	O
+isolated	O
+and	O
+partially	O
+characterized	O
+an	O
+avian	O
+fatty	B-GENE
+acid	I-GENE
+synthase	I-GENE
+gene	O
+.	O
+
+A	O
+new	O
+set	O
+of	O
+cDNA	O
+clones	O
+spanning	O
+approximately	O
+3	O
+.	O
+2	O
+kb	O
+was	O
+isolated	O
+from	O
+a	O
+lambda	O
+-	O
+ZAP	O
+goose	O
+liver	O
+cDNA	O
+library	O
+using	O
+the	O
+5	O
+'	O
+-	O
+most	O
+exon	O
+-	O
+containing	O
+fragment	O
+of	O
+the	O
+5	O
+'	O
+-	O
+most	O
+genomic	O
+DNA	O
+clone	O
+.	O
+
+Northern	O
+blotting	O
+analysis	O
+indicates	O
+that	O
+expression	O
+of	O
+the	O
+genes	O
+corresponding	O
+to	O
+these	O
+clones	O
+is	O
+confined	O
+to	O
+pollen	O
+tissue	O
+.	O
+
+Whereas	O
+cDNA	O
+hybridization	O
+to	O
+genomic	O
+DNA	O
+blots	O
+indicated	O
+a	O
+small	O
+subfamily	O
+of	O
+G0S19	B-GENE
+genes	I-GENE
+,	O
+simple	O
+patterns	O
+of	O
+bands	O
+indicated	O
+that	O
+most	O
+cDNAs	O
+,	O
+including	O
+G0S30	B-GENE
+cDNA	I-GENE
+,	O
+corresponded	O
+to	O
+single	O
+-	O
+copy	O
+genes	O
+.	O
+
+Lymphoproliferative	O
+disorders	O
+arising	O
+under	O
+immunosuppression	O
+with	O
+FK	O
+506	O
+:	O
+initial	O
+observations	O
+in	O
+a	O
+large	O
+transplant	O
+population	O
+.	O
+
+The	O
+Drosophila	B-GENE
+suppressor	I-GENE
+of	I-GENE
+sable	I-GENE
+gene	I-GENE
+encodes	O
+a	O
+polypeptide	O
+with	O
+regions	O
+similar	O
+to	O
+those	O
+of	O
+RNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+2	O
+:	O
+121	O
+-	O
+133	O
+,	O
+1988	O
+)	O
+.	O
+
+Using	O
+avidin	B-GENE
+-	I-GENE
+biotin	I-GENE
+complex	O
+DNA	O
+binding	O
+assays	O
+,	O
+a	O
+series	O
+of	O
+overlapping	O
+alpha	B-GENE
+promoter	I-GENE
+DNA	I-GENE
+sequences	I-GENE
+between	O
+-	O
+170	O
+to	O
+29	O
+basepairs	O
+were	O
+tested	O
+,	O
+but	O
+each	O
+failed	O
+to	O
+bind	O
+GR	B-GENE
+,	O
+whereas	O
+a	O
+control	O
+GRE	O
+avidly	O
+bound	O
+receptor	O
+.	O
+
+Sequence	O
+determination	O
+of	O
+isolated	O
+peptides	O
+suggested	O
+that	O
+Asn120	O
+is	O
+glycosylated	O
+,	O
+Asn65	O
+and	O
+Asn109	O
+glycosylated	O
+in	O
+some	O
+molecules	O
+but	O
+not	O
+in	O
+others	O
+,	O
+and	O
+Asn72	O
+not	O
+glycosylated	O
+.	O
+
+The	O
+DNA	O
+sequence	O
+conferring	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+was	O
+located	O
+in	O
+the	O
+proximal	O
+promoter	O
+region	O
+.	O
+
+The	O
+murine	B-GENE
+mutation	I-GENE
+dominant	I-GENE
+white	I-GENE
+spotting	I-GENE
+(	O
+W	B-GENE
+)	O
+is	O
+in	O
+the	O
+proto	O
+-	O
+oncogene	O
+,	O
+c	B-GENE
+-	I-GENE
+kit	I-GENE
+.	O
+
+The	O
+proteins	O
+differ	O
+in	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+a	O
+21	O
+-	O
+amino	O
+-	O
+acid	O
+sequence	O
+located	O
+24	O
+amino	O
+acids	O
+C	O
+terminal	O
+of	O
+the	O
+translational	O
+initiation	O
+codon	O
+.	O
+
+Our	O
+results	O
+also	O
+indicate	O
+the	O
+existence	O
+of	O
+sequences	O
+downstream	O
+of	O
+-	O
+0	O
+.	O
+11	O
+kb	O
+which	O
+can	O
+influence	O
+the	O
+pattern	O
+of	O
+tissue	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+HLA	B-GENE
+-	I-GENE
+B7	I-GENE
+gene	I-GENE
+and	O
+the	O
+ability	O
+of	O
+this	O
+gene	O
+to	O
+respond	O
+to	O
+gamma	B-GENE
+interferon	I-GENE
+.	O
+
+The	O
+SH2	B-GENE
+and	O
+SH3	B-GENE
+domains	I-GENE
+of	O
+pp60src	B-GENE
+direct	O
+stable	O
+association	O
+with	O
+tyrosine	O
+phosphorylated	O
+proteins	O
+p130	B-GENE
+and	O
+p110	B-GENE
+.	O
+
+These	O
+clones	O
+overlapped	O
+and	O
+contained	O
+the	O
+structural	O
+gene	O
+encoding	O
+the	O
+complete	O
+C5	B-GENE
+alpha	I-GENE
+-	I-GENE
+chain	I-GENE
+and	O
+90	O
+%	O
+of	O
+the	O
+beta	O
+-	O
+chain	O
+.	O
+
+The	O
+C5	B-GENE
+alpha	I-GENE
+-	I-GENE
+chain	I-GENE
+was	O
+encoded	O
+by	O
+49	O
+kilobases	O
+containing	O
+26	O
+exons	O
+;	O
+the	O
+beta	O
+-	O
+chain	O
+was	O
+encoded	O
+by	O
+29	O
+kilobases	O
+containing	O
+16	O
+exons	O
+.	O
+
+Heterozygous	O
+mutation	O
+in	O
+the	O
+G	O
++	O
+5	O
+position	O
+of	O
+intron	O
+33	O
+of	O
+the	O
+pro	B-GENE
+-	I-GENE
+alpha	I-GENE
+2	I-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+gene	I-GENE
+(	O
+COL1A2	B-GENE
+)	O
+that	O
+causes	O
+aberrant	O
+RNA	O
+splicing	O
+and	O
+lethal	O
+osteogenesis	O
+imperfecta	O
+.	O
+
+The	O
+nucleotide	O
+sequences	O
+of	O
+these	O
+genes	O
+differ	O
+at	O
+only	O
+nine	O
+positions	O
+,	O
+resulting	O
+in	O
+three	O
+amino	O
+acid	O
+differences	O
+.	O
+
+The	O
+protein	O
+predicted	O
+by	O
+the	O
+sequence	O
+of	O
+the	O
+human	B-GENE
+pim	I-GENE
+-	I-GENE
+1	I-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+shares	O
+extensive	O
+homology	O
+with	O
+known	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+protein	I-GENE
+kinases	I-GENE
+,	O
+and	O
+yet	O
+the	O
+human	B-GENE
+Pim	I-GENE
+-	I-GENE
+1	I-GENE
+enzyme	I-GENE
+has	O
+previously	O
+been	O
+reported	O
+to	O
+exhibit	O
+protein	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+activity	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+A	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+human	I-GENE
+pim	I-GENE
+-	I-GENE
+1	I-GENE
+cDNA	I-GENE
+was	O
+subcloned	O
+into	O
+the	O
+bacterial	O
+vector	O
+pGEX	O
+-	O
+2T	O
+and	O
+the	O
+Pim	B-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+expressed	O
+as	O
+a	O
+fusion	O
+product	O
+with	O
+bacterial	B-GENE
+glutathione	I-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+(	O
+GST	B-GENE
+)	O
+.	O
+
+The	O
+10	O
+kDa	O
+polypeptide	O
+was	O
+phosphorylated	O
+in	O
+vitro	O
+by	O
+incubating	O
+wheat	O
+etioplast	O
+membranes	O
+with	O
+[	O
+gamma	O
+32P	O
+]	O
+ATP	O
+.	O
+
+Homology	O
+with	O
+the	O
+human	O
+protein	O
+is	O
+only	O
+34	O
+%	O
+in	O
+the	O
+tandem	O
+repeat	O
+domain	O
+,	O
+mainly	O
+showing	O
+conservation	O
+of	O
+serines	O
+and	O
+threonines	O
+,	O
+presumed	O
+sites	O
+of	O
+O	O
+-	O
+linked	O
+carbohydrate	O
+attachment	O
+.	O
+
+In	O
+addition	O
+to	O
+targeting	O
+partially	O
+assembled	O
+Ti	B-GENE
+alpha	I-GENE
+-	I-GENE
+beta	I-GENE
+CD3	B-GENE
+gamma	I-GENE
+delta	I-GENE
+epsilon	I-GENE
+TCR	B-GENE
+complexes	I-GENE
+to	O
+the	O
+cell	O
+surface	O
+,	O
+CD3	B-GENE
+zeta	I-GENE
+appears	O
+to	O
+be	O
+essential	O
+for	O
+interleukin	B-GENE
+-	I-GENE
+2	I-GENE
+production	O
+after	O
+TCR	B-GENE
+stimulation	O
+with	O
+antigen	B-GENE
+/	I-GENE
+major	I-GENE
+histocompatibility	I-GENE
+complex	I-GENE
+.	O
+
+When	O
+desipramine	O
+was	O
+injected	O
+16	O
+hrs	O
+after	O
+fluoxetine	O
+injection	O
+,	O
+brain	O
+levels	O
+of	O
+desipramine	O
+were	O
+no	O
+longer	O
+elevated	O
+.	O
+
+Opposite	O
+effects	O
+of	O
+CYP1	B-GENE
+are	O
+observed	O
+in	O
+aerobic	O
+,	O
+heme	O
+-	O
+sufficient	O
+cells	O
+.	O
+
+A	O
+segmental	O
+analysis	O
+of	O
+the	O
+key	O
+regions	O
+of	O
+HLA	B-GENE
+-	I-GENE
+DR1	I-GENE
+that	O
+control	O
+T	O
+cell	O
+allorecognition	O
+was	O
+performed	O
+by	O
+using	O
+a	O
+series	O
+of	O
+transfected	O
+cell	O
+lines	O
+expressing	O
+the	O
+products	O
+of	O
+recombinant	O
+DRB	B-GENE
+/	O
+H	B-GENE
+-	I-GENE
+2Eb	I-GENE
+genes	O
+,	O
+paired	O
+with	O
+either	O
+DR	B-GENE
+alpha	I-GENE
+or	O
+H	B-GENE
+-	I-GENE
+2E	I-GENE
+alpha	I-GENE
+.	O
+
+We	O
+characterized	O
+cDNA	O
+clones	O
+specific	O
+for	O
+the	O
+extracellular	O
+matrix	O
+glycoprotein	O
+undulin	B-GENE
+.	O
+
+The	O
+alpha	B-GENE
+inhibin	I-GENE
+promoter	I-GENE
+containing	O
+a	O
+mutated	O
+CRE	O
+was	O
+not	O
+regulated	O
+by	O
+forskolin	O
+in	O
+granulosa	O
+cells	O
+and	O
+did	O
+not	O
+bind	O
+the	O
+CREB	B-GENE
+protein	I-GENE
+.	O
+
+Regulation	O
+of	O
+the	O
+alpha	B-GENE
+inhibin	I-GENE
+gene	I-GENE
+by	O
+cyclic	O
+adenosine	O
+3	O
+'	O
+,	O
+5	O
+'	O
+-	O
+monophosphate	O
+after	O
+transfection	O
+into	O
+rat	O
+granulosa	O
+cells	O
+.	O
+
+Comparison	O
+of	O
+the	O
+nucleotide	O
+sequences	O
+between	O
+the	O
+human	O
+and	O
+bovine	O
+DNA	O
+showed	O
+that	O
+the	O
+sequence	O
+similarity	O
+extended	O
+2400	O
+bp	O
+downstream	O
+from	O
+the	O
+coding	O
+region	O
+.	O
+
+In	O
+patients	O
+with	O
+osteomyelitis	O
+and	O
+joint	O
+empyema	O
+(	O
+n	O
+=	O
+48	O
+)	O
+PMN	B-GENE
+elastase	I-GENE
+had	O
+a	O
+sensitivity	O
+of	O
+77	O
+%	O
+,	O
+which	O
+was	O
+only	O
+exceeded	O
+by	O
+that	O
+of	O
+the	O
+unspecific	O
+erythrocyte	O
+sedimentation	O
+rate	O
+(	O
+sensitivity	O
+89	O
+%	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+the	O
+sulfhydryl	O
+group	O
+of	O
+certain	O
+angiotensin	B-GENE
+converting	I-GENE
+enzyme	I-GENE
+inhibitors	O
+can	O
+potentiate	O
+their	O
+effect	O
+on	O
+the	O
+endogenous	O
+nitrovasodilator	O
+EDRF	B-GENE
+.	O
+
+Pharmacokinetics	O
+of	O
+FK	O
+506	O
+in	O
+transplant	O
+patients	O
+.	O
+
+A	O
+second	O
+even	O
+more	O
+significant	O
+match	O
+to	O
+this	O
+E	O
+.	O
+coli	O
+region	O
+was	O
+found	O
+in	O
+the	O
+retroviral	B-GENE
+ribonuclease	I-GENE
+H	I-GENE
+(	O
+RNase	B-GENE
+H	I-GENE
+)	O
+domain	O
+,	O
+and	O
+corresponds	O
+precisely	O
+to	O
+a	O
+region	O
+that	O
+has	O
+been	O
+aligned	O
+by	O
+previous	O
+investigators	O
+with	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+RNase	I-GENE
+H	I-GENE
+,	O
+suggesting	O
+that	O
+Pol	B-GENE
+I	I-GENE
+helices	O
+O	O
+and	O
+P	O
+are	O
+homologous	O
+to	O
+helices	O
+A	O
+and	O
+D	O
+of	O
+the	O
+RNase	B-GENE
+H	I-GENE
+crystal	O
+structure	O
+,	O
+respectively	O
+.	O
+
+Analysis	O
+of	O
+the	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+suggests	O
+that	O
+CHIP28	B-GENE
+protein	I-GENE
+contains	O
+six	O
+bilayer	O
+-	O
+spanning	O
+domains	O
+,	O
+two	O
+exofacial	O
+potential	O
+N	O
+-	O
+glycosylation	O
+sites	O
+,	O
+and	O
+intracellular	O
+N	O
+and	O
+C	O
+termini	O
+.	O
+
+The	O
+qualitative	O
+concentrations	O
+of	O
+HCG	B-GENE
+had	O
+a	O
+sensitivity	O
+of	O
+37	O
+.	O
+5	O
+%	O
+and	O
+a	O
+specificity	O
+of	O
+100	O
+%	O
+.	O
+
+The	O
+reduced	O
+rate	O
+of	O
+F	O
+absorption	O
+and	O
+slower	O
+rise	O
+in	O
+plasma	O
+F	O
+concentration	O
+accompanying	O
+delayed	O
+gastric	O
+emptying	O
+indicate	O
+that	O
+passage	O
+of	O
+F	O
+into	O
+the	O
+small	O
+intestine	O
+is	O
+the	O
+major	O
+factor	O
+in	O
+rapid	O
+F	O
+absorption	O
+.	O
+
+The	O
+activity	O
+of	O
+serum	B-GENE
+lipase	I-GENE
+and	O
+amylase	B-GENE
+distinctly	O
+increased	O
+at	O
+3	O
+h	O
+and	O
+went	O
+up	O
+to	O
+the	O
+maximum	O
+at	O
+12	O
+h	O
+after	O
+injection	O
+of	O
+Na	O
+-	O
+Tc	O
+.	O
+
+They	O
+were	O
+checked	O
+for	O
+anti	B-GENE
+-	I-GENE
+HCV	I-GENE
+(	O
+anti	B-GENE
+-	I-GENE
+C100	I-GENE
+-	I-GENE
+3	I-GENE
+)	O
+with	O
+HCV	O
+EIA	O
+kit	O
+(	O
+Abbott	O
+Lab	O
+.	O
+,	O
+North	O
+Chicago	O
+,	O
+IL	O
+)	O
+.	O
+
+Diltiazem	O
+resulted	O
+in	O
+a	O
+significant	O
+increase	O
+in	O
+epicardial	O
+diameter	O
+(	O
++	O
+10	O
+%	O
+;	O
+p	O
+=	O
+0	O
+.	O
+001	O
+)	O
+and	O
+in	O
+coronary	O
+blood	O
+flow	O
+(	O
+CBF	O
+)	O
+(	O
++	O
+30	O
+%	O
+;	O
+p	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+The	O
+first	O
+transfusion	O
+resulted	O
+in	O
+a	O
+platelet	O
+increment	O
+to	O
+32	O
+Gpt	O
+/	O
+l	O
+(	O
+CCI	O
+11	O
+)	O
+.	O
+
+These	O
+risk	O
+factors	O
+can	O
+be	O
+divided	O
+into	O
+2	O
+groups	O
+:	O
+local	O
+vessel	O
+wall	O
+-	O
+related	O
+factors	O
+,	O
+and	O
+local	O
+(	O
+focal	O
+action	O
+)	O
+systemic	O
+factors	O
+.	O
+
+Epidemiology	O
+and	O
+prevention	O
+of	O
+hospital	O
+infections	O
+in	O
+the	O
+Local	O
+Health	O
+Unit	O
+of	O
+Sassari	O
+:	O
+profile	O
+of	O
+bacterial	O
+resistance	O
+and	O
+antimicrobial	O
+agents	O
+of	O
+large	O
+usage	O
+.	O
+
+PRDII	B-GENE
+-	I-GENE
+BF1	I-GENE
+-	I-GENE
+derived	I-GENE
+cDNAs	I-GENE
+did	O
+not	O
+result	O
+in	O
+stimulation	O
+of	O
+either	O
+basal	O
+or	O
+tat	B-GENE
+-	O
+induced	O
+activated	O
+gene	O
+expression	O
+.	O
+
+Vaccinia	O
+virus	O
+(	O
+VV	O
+)	O
+is	O
+a	O
+potent	O
+immunogen	O
+,	O
+but	O
+the	O
+nature	O
+of	O
+VV	O
+proteins	O
+involved	O
+in	O
+the	O
+activation	O
+of	O
+the	O
+immune	O
+response	O
+of	O
+the	O
+host	O
+is	O
+not	O
+yet	O
+known	O
+.	O
+
+Max	B-GENE
+:	O
+functional	O
+domains	O
+and	O
+interaction	O
+with	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+.	O
+
+86	O
+:	O
+3199	O
+-	O
+3203	O
+)	O
+or	O
+G1	O
+to	O
+S	O
+phase	O
+(	O
+Reilly	O
+,	O
+C	O
+.	O
+
+Substitutions	O
+introduced	O
+at	O
+bases	O
+surrounding	O
+the	O
+ICR2	B-GENE
+motif	I-GENE
+yielded	O
+levels	O
+of	O
+pRNA	O
+replication	O
+that	O
+differed	O
+,	O
+depending	O
+on	O
+the	O
+maintenance	O
+of	O
+a	O
+putative	O
+5	O
+'	O
+stem	O
+-	O
+loop	O
+structure	O
+in	O
+the	O
+positive	O
+strand	O
+of	O
+the	O
+viral	O
+genome	O
+.	O
+
+Zn	O
+(	O
+II	O
+)	O
+coordination	O
+domain	O
+mutants	O
+of	O
+T4	O
+gene	B-GENE
+32	I-GENE
+protein	O
+.	O
+
+Zn	O
+(	O
+II	O
+)	O
+coordination	O
+domain	O
+mutants	O
+of	O
+T4	B-GENE
+gene	I-GENE
+32	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+tissue	O
+specificity	O
+of	O
+gene	O
+expression	O
+was	O
+identical	O
+to	O
+that	O
+described	O
+previously	O
+for	O
+the	O
+CaMV	B-GENE
+35S	I-GENE
+domain	I-GENE
+B	I-GENE
+enhancer	I-GENE
+element	I-GENE
+.	O
+
+The	O
+pathophysiology	O
+and	O
+clinical	O
+management	O
+of	O
+acute	O
+brain	O
+injury	O
+in	O
+infancy	O
+and	O
+childhood	O
+are	O
+presented	O
+using	O
+acute	O
+traumatic	O
+brain	O
+injury	O
+as	O
+a	O
+model	O
+.	O
+
+Transcripts	O
+from	O
+a	O
+second	O
+POU	B-GENE
+-	I-GENE
+domain	I-GENE
+gene	I-GENE
+,	O
+Oct	B-GENE
+-	I-GENE
+25	I-GENE
+,	O
+were	O
+present	O
+at	O
+low	O
+levels	O
+in	O
+oocytes	O
+and	O
+early	O
+embryos	O
+and	O
+were	O
+dramatically	O
+upregulated	O
+during	O
+early	O
+gastrulation	O
+.	O
+
+The	O
+genome	O
+of	O
+Thogoto	O
+virus	O
+comprises	O
+six	O
+segments	O
+of	O
+single	O
+-	O
+stranded	O
+,	O
+negative	O
+sense	O
+RNA	O
+.	O
+
+These	O
+tumors	O
+were	O
+classified	O
+into	O
+three	O
+broad	O
+groups	O
+:	O
+I	O
+,	O
+cystadenoma	O
+;	O
+II	O
+,	O
+cystadenocarcinoma	O
+;	O
+and	O
+III	O
+,	O
+adenocarcinoma	O
+with	O
+mucin	B-GENE
+production	O
+or	O
+an	O
+associated	O
+cyst	O
+.	O
+
+Immunostaining	O
+of	O
+cells	O
+transfected	O
+with	O
+these	O
+constructs	O
+revealed	O
+that	O
+both	O
+the	O
+myristoylated	O
+and	O
+nonmyristoylated	O
+mutants	O
+were	O
+localized	O
+in	O
+nuclei	O
+,	O
+whereas	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+PKC	I-GENE
+alpha	I-GENE
+was	O
+primarily	O
+cytoplasmic	O
+and	O
+perinuclear	O
+.	O
+
+We	O
+have	O
+partially	O
+sequenced	O
+the	O
+RAP74	B-GENE
+protein	I-GENE
+from	O
+purified	O
+HeLa	O
+cells	O
+,	O
+cloned	O
+its	O
+complementary	O
+DNA	O
+and	O
+shown	O
+that	O
+its	O
+translation	O
+product	O
+can	O
+interact	O
+with	O
+RAP30	B-GENE
+in	O
+vitro	O
+as	O
+well	O
+as	O
+in	O
+vivo	O
+.	O
+
+Effects	O
+of	O
+thromboxane	B-GENE
+synthetase	I-GENE
+inhibition	O
+on	O
+postburn	O
+mesenteric	O
+vascular	O
+resistance	O
+and	O
+the	O
+rate	O
+of	O
+bacterial	O
+translocation	O
+in	O
+a	O
+chronic	O
+porcine	O
+model	O
+.	O
+
+The	O
+primary	O
+pancreatic	O
+insult	O
+seemed	O
+to	O
+be	O
+unaffected	O
+by	O
+the	O
+treatment	O
+,	O
+because	O
+neither	O
+the	O
+rise	O
+in	O
+plasma	B-GENE
+lipase	I-GENE
+nor	O
+the	O
+development	O
+of	O
+ascites	O
+or	O
+the	O
+extension	O
+of	O
+the	O
+pancreatic	O
+necrosis	O
+were	O
+diminished	O
+.	O
+
+The	O
+size	O
+of	O
+the	O
+mutant	O
+molecule	O
+corresponds	O
+to	O
+the	O
+unprocessed	O
+cytoplasmic	O
+precursor	O
+(	O
+pre	B-GENE
+-	I-GENE
+super	I-GENE
+-	I-GENE
+pro	I-GENE
+-	I-GENE
+PrB	I-GENE
+)	O
+,	O
+as	O
+detected	O
+in	O
+sec61	B-GENE
+mutants	I-GENE
+,	O
+when	O
+translocation	O
+into	O
+the	O
+endoplasmic	O
+reticulum	O
+is	O
+blocked	O
+.	O
+
+Thus	O
+,	O
+the	O
+active	O
+-	O
+site	O
+mutation	O
+prevents	O
+the	O
+wild	O
+-	O
+type	O
+processing	O
+of	O
+the	O
+N	O
+-	O
+glycosylated	O
+73	O
+-	O
+kDa	O
+precursor	O
+of	O
+PrB	B-GENE
+to	O
+the	O
+41	B-GENE
+.	I-GENE
+5	I-GENE
+kDa	I-GENE
+pro	I-GENE
+-	I-GENE
+PrB	I-GENE
+in	O
+the	O
+endoplasmic	O
+reticulum	O
+.	O
+
+The	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+exhibited	O
+70	O
+%	O
+identity	O
+to	O
+that	O
+of	O
+Bacillus	B-GENE
+stearothermophilus	I-GENE
+TyrTS	I-GENE
+and	O
+55	O
+%	O
+identity	O
+to	O
+that	O
+of	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+TyrTS	I-GENE
+,	O
+while	O
+identity	O
+to	O
+a	O
+second	O
+cryptic	O
+B	B-GENE
+.	I-GENE
+subtilis	I-GENE
+TyrTS	I-GENE
+gene	I-GENE
+,	O
+designated	O
+tyrZ	B-GENE
+,	O
+was	O
+only	O
+27	O
+%	O
+.	O
+
+Heat	O
+-	O
+inducible	O
+CAT	B-GENE
+activity	O
+was	O
+detectable	O
+when	O
+additional	O
+sequences	O
+from	O
+the	O
+native	O
+promoter	O
+containing	O
+three	O
+CCAAT	O
+boxes	O
+and	O
+a	O
+single	O
+HSE	O
+were	O
+present	O
+in	O
+the	O
+constructions	O
+.	O
+
+SETTING	O
+-	O
+-	O
+Women	O
+,	O
+Infants	O
+,	O
+and	O
+Children	O
+clinics	O
+in	O
+Minneapolis	O
+,	O
+Minn	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+effectiveness	O
+of	O
+monoamine	B-GENE
+oxidase	I-GENE
+inhibitors	O
+(	O
+MAOIs	O
+)	O
+in	O
+tricyclic	O
+resistant	O
+depression	O
+has	O
+received	O
+surprisingly	O
+little	O
+systematic	O
+study	O
+.	O
+
+The	O
+upstream	O
+delta	O
+-	O
+alpha	O
+breakpoint	O
+is	O
+flanked	O
+by	O
+the	O
+direct	O
+repeats	O
+of	O
+the	O
+acceptor	O
+splice	O
+site	O
+,	O
+whereas	O
+the	O
+down	O
+-	O
+stream	O
+alpha	O
+-	O
+delta	O
+breakpoint	O
+is	O
+located	O
+in	O
+the	O
+adjacent	O
+intron	O
+.	O
+
+Patients	O
+with	O
+moderate	O
+PDDAT	O
+were	O
+impaired	O
+on	O
+all	O
+serial	O
+positions	O
+for	O
+both	O
+spatial	O
+order	O
+and	O
+spatial	O
+recognition	O
+memory	O
+.	O
+
+Bone	O
+and	O
+bones	O
+.	O
+
+Management	O
+often	O
+involves	O
+beta	O
+-	O
+and	O
+calcium	O
+channel	O
+blocking	O
+drugs	O
+or	O
+type	O
+IC	O
+antiarrhythmic	O
+drugs	O
+.	O
+
+To	O
+overcome	O
+this	O
+problem	O
+,	O
+we	O
+have	O
+overexpressed	O
+Kex2p	B-GENE
+using	O
+the	O
+baculovirus	O
+/	O
+insect	O
+cell	O
+expression	O
+system	O
+.	O
+
+J	O
+.	O
+
+The	O
+major	B-GENE
+49	I-GENE
+-	I-GENE
+kDa	I-GENE
+core	I-GENE
+protein	I-GENE
+in	O
+the	O
+liver	O
+HSPG	B-GENE
+preparation	O
+was	O
+found	O
+to	O
+be	O
+reactive	O
+to	O
+an	O
+antibody	O
+that	O
+specifically	O
+recognizes	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+fibroglycan	B-GENE
+.	O
+
+While	O
+no	O
+obvious	O
+transmembrane	O
+regions	O
+were	O
+identified	O
+,	O
+several	O
+short	O
+hydrophobic	O
+amino	O
+acid	O
+stretches	O
+were	O
+found	O
+to	O
+be	O
+localized	O
+in	O
+and	O
+around	O
+the	O
+Pro	O
+II	O
+region	O
+,	O
+and	O
+these	O
+may	O
+be	O
+responsible	O
+for	O
+attachment	O
+of	O
+precursors	O
+to	O
+membranes	O
+.	O
+
+Toxicity	O
+was	O
+mild	O
+,	O
+mainly	O
+consisting	O
+of	O
+emesis	O
+(	O
+81	O
+%	O
+of	O
+the	O
+patients	O
+;	O
+66	O
+%	O
+of	O
+the	O
+courses	O
+)	O
+,	O
+leukopenia	O
+of	O
+World	O
+Health	O
+Organization	O
+(	O
+WHO	O
+)	O
+grade	O
+1	O
+to	O
+2	O
+(	O
+47	O
+%	O
+of	O
+the	O
+patients	O
+;	O
+18	O
+%	O
+of	O
+the	O
+courses	O
+)	O
+,	O
+and	O
+thrombocytopenia	O
+(	O
+12	O
+%	O
+of	O
+the	O
+patients	O
+;	O
+3	O
+%	O
+of	O
+the	O
+courses	O
+)	O
+.	O
+
+This	O
+study	O
+confirms	O
+,	O
+although	O
+individual	O
+reaction	O
+is	O
+remarkably	O
+different	O
+,	O
+transportation	O
+as	O
+a	O
+potent	O
+stressor	O
+for	O
+Beagle	O
+dogs	O
+.	O
+
+RESULTS	O
+:	O
+Plasma	B-GENE
+AVP	I-GENE
+responses	O
+to	O
+osmotic	O
+stimulation	O
+,	O
+and	O
+non	O
+-	O
+osmotic	O
+inhibition	O
+by	O
+drinking	O
+,	O
+were	O
+normal	O
+in	O
+patients	O
+with	O
+compulsive	O
+water	O
+drinking	O
+.	O
+
+The	O
+fragments	O
+of	O
+each	O
+region	O
+were	O
+amplified	O
+by	O
+polymerase	O
+chain	O
+reaction	O
+and	O
+analyzed	O
+by	O
+gel	O
+electrophoresis	O
+to	O
+detect	O
+single	O
+-	O
+strand	O
+conformation	O
+polymorphism	O
+.	O
+
+The	O
+csbA	B-GENE
+fusion	I-GENE
+was	O
+maximally	O
+expressed	O
+during	O
+early	O
+stationary	O
+phase	O
+in	O
+cells	O
+grown	O
+in	O
+Luria	O
+broth	O
+containing	O
+5	O
+%	O
+glucose	O
+and	O
+0	O
+.	O
+2	O
+%	O
+glutamine	O
+.	O
+
+The	O
+constraints	O
+of	O
+primase	B-GENE
+recognition	I-GENE
+sequences	I-GENE
+,	O
+nucleotide	O
+substrate	O
+requirements	O
+,	O
+and	O
+the	O
+effects	O
+of	O
+additional	O
+proteins	O
+on	O
+oligoribonucleotide	O
+synthesis	O
+by	O
+the	O
+63	B-GENE
+-	I-GENE
+kDa	I-GENE
+gene	I-GENE
+4	I-GENE
+protein	I-GENE
+have	O
+been	O
+examined	O
+using	O
+templates	O
+of	O
+defined	O
+sequence	O
+.	O
+
+Thrombolytic	O
+therapy	O
+in	O
+spontaneous	O
+coronary	O
+artery	O
+dissection	O
+.	O
+
+A	O
+prospective	O
+trial	O
+was	O
+carried	O
+out	O
+in	O
+156	O
+unselected	O
+patients	O
+(	O
+41	O
+men	O
+,	O
+mean	O
+age	O
+67	O
+.	O
+5	O
+years	O
+,	O
+115	O
+women	O
+,	O
+mean	O
+age	O
+71	O
+.	O
+4	O
+years	O
+)	O
+who	O
+had	O
+undergone	O
+total	O
+hip	O
+joint	O
+replacement	O
+because	O
+of	O
+degenerative	O
+or	O
+inflammatory	O
+arthritis	O
+or	O
+fracture	O
+of	O
+the	O
+neck	O
+of	O
+the	O
+femur	O
+.	O
+
+When	O
+both	O
+lesions	O
+were	O
+complete	O
+lateral	O
+hemisections	O
+in	O
+weanling	O
+operates	O
+,	O
+little	O
+behavioral	O
+recovery	O
+was	O
+observed	O
+,	O
+similar	O
+to	O
+complete	O
+spinal	O
+cord	O
+transection	O
+(	O
+N	O
+=	O
+3	O
+)	O
+.	O
+
+Human	O
+SRF	B-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+:	O
+DNA	O
+-	O
+binding	O
+properties	O
+and	O
+potential	O
+regulatory	O
+targets	O
+.	O
+
+We	O
+have	O
+isolated	O
+cDNAs	O
+for	O
+a	O
+gene	O
+coding	O
+for	O
+a	O
+G	B-GENE
+protein	I-GENE
+alpha	I-GENE
+subunit	I-GENE
+from	I-GENE
+tomato	I-GENE
+(	O
+Lycopersicon	O
+esculentum	O
+,	O
+cv	O
+.	O
+
+Growth	O
+factor	O
+stimulation	O
+of	O
+cells	O
+causes	O
+the	O
+phosphorylation	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+transcriptional	I-GENE
+activation	I-GENE
+domain	I-GENE
+at	O
+Ser62	O
+within	O
+a	O
+proline	O
+-	O
+rich	O
+region	O
+that	O
+is	O
+highly	O
+conserved	O
+among	O
+members	O
+of	O
+the	O
+Myc	B-GENE
+family	I-GENE
+(	O
+Alvarez	O
+,	O
+E	O
+.	O
+,	O
+Northwood	O
+,	O
+I	O
+.	O
+C	O
+.	O
+,	O
+Gonzalez	O
+,	O
+F	O
+.	O
+
+The	O
+authors	O
+evaluated	O
+the	O
+potential	O
+for	O
+thrombotic	O
+complications	O
+arising	O
+from	O
+implantation	O
+of	O
+a	O
+ventricular	O
+assist	O
+device	O
+(	O
+Sarns	O
+/	O
+3M	O
+-	O
+VAD	O
+)	O
+in	O
+four	O
+calves	O
+.	O
+
+Cardiac	O
+output	O
+(	O
+CO	O
+)	O
+was	O
+significantly	O
+higher	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+0005	O
+)	O
+in	O
+the	O
+MBBF	O
+group	O
+.	O
+
+Amino	O
+acid	O
+residues	O
+147	O
+-	O
+167	O
+of	O
+the	O
+previously	O
+reported	O
+sequence	O
+are	O
+replaced	O
+by	O
+new	O
+residues	O
+147	O
+to	O
+150	O
+.	O
+
+Transcriptional	O
+activation	O
+by	O
+the	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+Tat	I-GENE
+protein	I-GENE
+requires	O
+specific	O
+residues	O
+in	O
+the	O
+hexanucleotide	O
+loop	O
+and	O
+trinucleotide	O
+bulge	O
+of	O
+the	O
+TAR	B-GENE
+RNA	O
+stem	O
+-	O
+loop	O
+structure	O
+found	O
+in	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+leader	O
+of	O
+all	O
+viral	O
+transcripts	O
+.	O
+
+These	O
+results	O
+strongly	O
+suggest	O
+that	O
+locally	O
+-	O
+applied	O
+TTC	O
+in	O
+combination	O
+with	O
+FDBA	O
+enhances	O
+new	O
+bone	O
+formation	O
+in	O
+experimental	O
+alveolar	O
+bone	O
+defects	O
+.	O
+
+As	O
+an	O
+initial	O
+step	O
+towards	O
+the	O
+characterization	O
+of	O
+replicative	O
+DNA	B-GENE
+polymerases	I-GENE
+of	I-GENE
+trypanosomes	I-GENE
+,	O
+we	O
+have	O
+cloned	O
+,	O
+sequenced	O
+and	O
+examined	O
+the	O
+expression	O
+of	O
+the	O
+Trypanosoma	O
+(	O
+Trypanozoon	O
+)	O
+brucei	O
+brucei	O
+gene	O
+that	O
+encodes	O
+the	O
+DNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+catalytic	I-GENE
+core	I-GENE
+(	O
+pol	B-GENE
+alpha	I-GENE
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+there	O
+was	O
+a	O
+significant	O
+increase	O
+in	O
+postdexamethasone	O
+cortical	O
+concentrations	O
+with	O
+age	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+;	O
+r	O
+=	O
+0	O
+.	O
+31	O
+)	O
+.	O
+
+The	O
+volume	O
+fraction	O
+(	O
+Vv	O
+)	O
+and	O
+number	O
+/	O
+mm2	O
+(	O
+Na	O
+)	O
+of	O
+all	O
+capillaries	O
+(	O
+perfused	O
+and	O
+nonperfused	O
+)	O
+in	O
+a	O
+given	O
+area	O
+of	O
+brain	O
+were	O
+determined	O
+after	O
+staining	O
+for	O
+alkaline	B-GENE
+phosphatase	I-GENE
+.	O
+
+Airway	O
+pressure	O
+and	O
+air	O
+flow	O
+were	O
+measured	O
+at	O
+the	O
+endotracheal	O
+tube	O
+in	O
+13	O
+children	O
+on	O
+a	O
+variety	O
+of	O
+ventilators	O
+.	O
+
+Appl	O
+.	O
+
+Issues	O
+of	O
+distribution	O
+of	O
+kinetic	O
+energy	O
+of	O
+traumatizing	O
+object	O
+in	O
+direct	O
+contact	O
+interaction	O
+with	O
+head	O
+during	O
+impact	O
+are	O
+discussed	O
+from	O
+position	O
+of	O
+biomechanics	O
+.	O
+
+CONCLUSION	O
+:	O
+Monitoring	O
+SpO2	O
+at	O
+the	O
+nasal	O
+septum	O
+site	O
+is	O
+more	O
+reliable	O
+than	O
+monitoring	O
+it	O
+at	O
+the	O
+finger	O
+site	O
+in	O
+hypothermic	O
+patients	O
+.	O
+
+The	O
+granules	O
+grew	O
+as	O
+the	O
+melted	O
+material	O
+immersed	O
+into	O
+the	O
+void	O
+space	O
+among	O
+the	O
+adhered	O
+particles	O
+.	O
+
+Hence	O
+,	O
+the	O
+uPA	B-GENE
+promoter	I-GENE
+contains	O
+multiple	O
+weak	O
+cis	O
+-	O
+acting	O
+elements	O
+distributed	O
+over	O
+7	O
+.	O
+0	O
+kb	O
+5	O
+'	O
+to	O
+the	O
+translation	O
+start	O
+site	O
+.	O
+
+Substituting	O
+a	O
+Ser	O
+for	O
+Gly69	O
+or	O
+a	O
+Glu	O
+for	O
+Lys	O
+71	O
+in	O
+the	O
+conserved	O
+TGEK	B-GENE
+tetrapeptide	I-GENE
+in	O
+finger	O
+II	O
+of	O
+TFIIIA	B-GENE
+resulted	O
+in	O
+the	O
+loss	O
+of	O
+DNA	O
+binding	O
+.	O
+
+P	O
+.	O
+
+In	O
+one	O
+,	O
+exploratory	O
+behavior	O
+(	O
+assessed	O
+by	O
+hole	O
+pokes	O
+)	O
+and	O
+locomotion	O
+were	O
+assessed	O
+during	O
+a	O
+10	O
+-	O
+min	O
+test	O
+session	O
+.	O
+
+12	O
+-	O
+O	O
+-	O
+Tetradecanoylphorbol	O
+13	O
+-	O
+acetate	O
+was	O
+found	O
+to	O
+inhibit	O
+rapidly	O
+and	O
+potently	O
+the	O
+expression	O
+of	O
+mRNAs	O
+coding	O
+for	O
+the	O
+myogenic	O
+regulators	O
+CMD1	B-GENE
+and	O
+myogenin	B-GENE
+.	O
+
+In	O
+Xenopus	O
+laevis	O
+,	O
+the	O
+gene	O
+encoding	O
+the	O
+elongation	B-GENE
+factor	I-GENE
+1	I-GENE
+-	I-GENE
+alpha	I-GENE
+variant	I-GENE
+EF	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+O	I-GENE
+,	O
+where	O
+O	O
+stands	O
+for	O
+oocyte	O
+,	O
+is	O
+expressed	O
+in	O
+oocytes	O
+and	O
+early	O
+embryos	O
+.	O
+
+These	O
+introns	O
+belong	O
+to	O
+the	O
+class	O
+of	O
+nuclear	O
+pre	O
+-	O
+mRNA	O
+introns	O
+and	O
+contain	O
+typical	O
+5	O
+'	O
+-	O
+and	O
+3	O
+'	O
+-	O
+consensus	O
+sequences	O
+,	O
+as	O
+well	O
+as	O
+unique	O
+features	O
+.	O
+
+The	O
+mRNA	O
+identified	O
+in	O
+both	O
+human	O
+and	O
+rat	O
+cells	O
+with	O
+the	O
+human	B-GENE
+clathrin	I-GENE
+clone	O
+revealed	O
+transcripts	O
+of	O
+approximately	O
+6	O
+.	O
+5	O
+kb	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+the	O
+predicted	O
+180	O
+kDa	O
+molecular	O
+weight	O
+of	O
+the	O
+clathrin	B-GENE
+heavy	I-GENE
+chain	I-GENE
+.	O
+
+In	O
+this	O
+report	O
+,	O
+almost	O
+6	O
+kb	O
+of	O
+DNA	O
+sequence	O
+is	O
+presented	O
+,	O
+including	O
+1251	O
+bp	O
+5	O
+'	O
+to	O
+the	O
+gene	O
+,	O
+over	O
+4	O
+kb	O
+of	O
+exon	O
+and	O
+exon	O
+-	O
+intron	O
+junctions	O
+,	O
+and	O
+583	O
+bp	O
+3	O
+'	O
+to	O
+the	O
+gene	O
+.	O
+
+Antibodies	O
+specific	O
+to	O
+rE12	B-GENE
+and	O
+rNFIL	B-GENE
+-	I-GENE
+6	I-GENE
+disrupt	O
+nucleoprotein	O
+complexes	O
+with	O
+these	O
+DNA	O
+-	O
+binding	O
+sites	O
+,	O
+confirming	O
+the	O
+interaction	O
+of	O
+native	O
+in	O
+vivo	O
+factors	O
+.	O
+
+A	O
+method	O
+is	O
+described	O
+for	O
+detecting	O
+targeted	O
+events	O
+at	O
+the	O
+mu	B-GENE
+heavy	I-GENE
+chain	I-GENE
+gene	I-GENE
+which	O
+relies	O
+on	O
+co	O
+-	O
+conversion	O
+(	O
+or	O
+co	O
+-	O
+exchange	O
+)	O
+of	O
+a	O
+point	O
+mutation	O
+with	O
+a	O
+selectable	O
+marker	O
+contained	O
+on	O
+a	O
+replacement	O
+vector	O
+.	O
+
+Allergenic	O
+activity	O
+of	O
+allergen	O
+extract	O
+Ambrosia	O
+elatior	O
+(	O
+AE	O
+)	O
+was	O
+tested	O
+in	O
+fifteen	O
+volunteers	O
+extremely	O
+sensitive	O
+to	O
+the	O
+allergen	O
+.	O
+
+This	O
+study	O
+was	O
+aimed	O
+at	O
+assessing	O
+whether	O
+c	O
+-	O
+DDP	O
+administration	O
+immediately	O
+before	O
+radiotherapy	O
+could	O
+increase	O
+frequency	O
+and	O
+duration	O
+of	O
+objective	O
+responses	O
+,	O
+as	O
+well	O
+as	O
+survival	O
+,	O
+in	O
+patients	O
+affected	O
+with	O
+locally	O
+advanced	O
+stages	O
+of	O
+squamous	O
+carcinomas	O
+of	O
+the	O
+head	O
+and	O
+neck	O
+.	O
+
+Two	O
+potential	O
+regulatory	O
+sequences	O
+for	O
+DNA	O
+binding	O
+proteins	O
+were	O
+found	O
+in	O
+the	O
+non	O
+-	O
+coding	O
+5	O
+'	O
+region	O
+:	O
+a	O
+HAP2	B-GENE
+/	O
+HAP3	B-GENE
+consensus	O
+recognition	O
+sequence	O
+at	O
+nucleotide	O
+-	O
+154	O
+and	O
+a	O
+BAF1	B-GENE
+consensus	I-GENE
+recognition	I-GENE
+sequence	I-GENE
+at	O
+nucleotide	O
+-	O
+136	O
+.	O
+
+We	O
+exploit	O
+the	O
+properties	O
+of	O
+LexA	B-GENE
+fusion	I-GENE
+proteins	I-GENE
+to	O
+study	O
+the	O
+dimerization	O
+and	O
+DNA	O
+-	O
+contacting	O
+domains	O
+of	O
+cRel	B-GENE
+.	O
+
+Plasma	O
+lipid	O
+and	O
+lipoprotein	O
+profiles	O
+were	O
+compared	O
+in	O
+elderly	O
+female	O
+runners	O
+(	O
+RU	O
+:	O
+n	O
+=	O
+15	O
+,	O
+aged	O
+66	O
++	O
+/	O
+-	O
+5	O
+years	O
+,	O
+body	O
+fat	O
+20	O
++	O
+/	O
+-	O
+4	O
+%	O
+,	O
+training	O
+distance	O
+35	O
++	O
+/	O
+-	O
+15	O
+km	O
+week	O
+-	O
+1	O
+,	O
+VO2max	O
+36	O
++	O
+/	O
+-	O
+4	O
+ml	O
+kg	O
+-	O
+1	O
+min	O
+-	O
+1	O
+,	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+and	O
+age	O
+-	O
+matched	O
+untrained	O
+women	O
+(	O
+UT	O
+:	O
+n	O
+=	O
+28	O
+,	O
+66	O
++	O
+/	O
+-	O
+4	O
+years	O
+,	O
+body	O
+fat	O
+26	O
++	O
+/	O
+-	O
+6	O
+%	O
+,	O
+VO2max	O
+26	O
++	O
+/	O
+-	O
+3	O
+ml	O
+kg	O
+-	O
+1	O
+min	O
+-	O
+1	O
+)	O
+.	O
+
+Fundamental	O
+and	O
+clinical	O
+evaluation	O
+of	O
+equilibrium	O
+dialysis	O
+-	O
+-	O
+radioimmunoassay	O
+system	O
+for	O
+measurement	O
+of	O
+serum	O
+free	O
+thyroxine	O
+
+We	O
+conclude	O
+that	O
+TA	O
+caused	O
+a	O
+specific	O
+decrease	O
+in	O
+AGD	O
+on	O
+GD	O
+20	O
+that	O
+was	O
+largely	O
+reversed	O
+by	O
+PCD	O
+23	O
+.	O
+
+When	O
+examined	O
+as	O
+adults	O
+(	O
+8	O
+weeks	O
+old	O
+)	O
+,	O
+the	O
+external	O
+genitalia	O
+of	O
+TA	O
+-	O
+exposed	O
+offspring	O
+were	O
+normal	O
+.	O
+
+After	O
+PTCA	O
+,	O
+ejection	O
+fraction	O
+increased	O
+from	O
+54	O
++	O
+/	O
+-	O
+8	O
+%	O
+to	O
+59	O
++	O
+/	O
+-	O
+8	O
+%	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+regional	O
+function	O
+improved	O
+significantly	O
+(	O
+maximal	O
+standard	O
+deviation	O
+before	O
+PTCA	O
+:	O
+2	O
+.	O
+8	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+;	O
+after	O
+PTCA	O
+:	O
+1	O
+.	O
+9	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+-	O
+segments	O
+below	O
+the	O
+first	O
+standard	O
+deviation	O
+before	O
+PTCA	O
+:	O
+31	O
++	O
+/	O
+-	O
+16	O
+;	O
+after	O
+PTCA	O
+:	O
+19	O
++	O
+/	O
+-	O
+17	O
+)	O
+.	O
+
+The	O
+alcoholic	O
+patient	O
+,	O
+his	O
+work	O
+and	O
+the	O
+subjectivity	O
+of	O
+the	O
+period	O
+
+These	O
+data	O
+suggest	O
+that	O
+the	O
+combined	O
+treatment	O
+with	O
+a	O
+thromboxane	B-GENE
+synthetase	I-GENE
+inhibitor	O
+and	O
+a	O
+thromboxane	B-GENE
+receptor	I-GENE
+antagonist	O
+provides	O
+a	O
+better	O
+protection	O
+against	O
+digoxin	O
+intoxication	O
+than	O
+with	O
+either	O
+agent	O
+alone	O
+.	O
+
+A	O
+330	O
+-	O
+kb	O
+YAC	O
+,	O
+A148A7	O
+,	O
+spanned	O
+from	O
+the	O
+HLA	B-GENE
+-	O
+DQA1	B-GENE
+locus	O
+through	O
+the	O
+Y3	B-GENE
+/	O
+Ring	B-GENE
+4	I-GENE
+locus	O
+and	O
+extended	O
+at	O
+least	O
+130	O
+kb	O
+centromeric	O
+of	O
+YAC	O
+B1D12	O
+.	O
+
+Adverse	O
+foetal	O
+outcome	O
+in	O
+specific	O
+IgM	B-GENE
+positive	O
+Chlamydia	O
+trachomatis	O
+infection	O
+in	O
+pregnancy	O
+.	O
+
+Using	O
+an	O
+image	O
+-	O
+processing	O
+computer	O
+,	O
+regional	O
+LV	O
+time	O
+-	O
+density	O
+curves	O
+were	O
+constructed	O
+for	O
+one	O
+cardiac	O
+cycle	O
+.	O
+
+In	O
+a	O
+second	O
+patient	O
+the	O
+VT	O
+became	O
+nonsustained	O
+.	O
+
+The	O
+possible	O
+mechanisms	O
+underlying	O
+differences	O
+in	O
+post	O
+-	O
+tetanic	O
+effects	O
+from	O
+muscle	O
+and	O
+cutaneous	O
+afferents	O
+in	O
+adults	O
+and	O
+neonates	O
+are	O
+discussed	O
+.	O
+
+We	O
+examined	O
+behavioral	O
+alterations	O
+in	O
+the	O
+brown	O
+cockroach	O
+,	O
+Periplaneta	O
+brunnea	O
+,	O
+infected	O
+with	O
+the	O
+acanthocephalan	O
+,	O
+Moniliformis	O
+moniliformis	O
+.	O
+
+First	O
+,	O
+the	O
+finding	O
+of	O
+a	O
+monomeric	O
+Alu	B-GENE
+family	O
+repeat	O
+at	O
+the	O
+junction	O
+between	O
+nonhomology	O
+block	O
+I	O
+and	O
+homology	O
+block	O
+Y	O
+of	O
+the	O
+alpha	B-GENE
+2	I-GENE
+gene	I-GENE
+-	I-GENE
+containing	I-GENE
+unit	I-GENE
+in	I-GENE
+rhesus	I-GENE
+macaque	I-GENE
+suggests	O
+that	O
+the	O
+dimeric	O
+Alu	B-GENE
+family	O
+repeat	O
+,	O
+Alu	B-GENE
+3	I-GENE
+,	O
+at	O
+the	O
+orthologous	O
+position	O
+in	O
+human	O
+was	O
+generated	O
+by	O
+insertion	O
+of	O
+a	O
+monomeric	O
+Alu	B-GENE
+family	O
+repeat	O
+into	O
+the	O
+3	O
+'	O
+end	O
+of	O
+another	O
+preexisting	O
+Alu	B-GENE
+family	O
+repeat	O
+.	O
+
+The	O
+sequence	O
+of	O
+the	O
+repressor	O
+locus	O
+,	O
+c	O
+,	O
+of	O
+the	O
+Streptomyces	O
+temperate	O
+phage	O
+,	O
+phi	O
+C31	O
+,	O
+was	O
+shown	O
+previously	O
+to	O
+contain	O
+an	O
+open	O
+reading	O
+frame	O
+encoding	O
+a	O
+74	O
+kDa	O
+protein	O
+.	O
+
+This	O
+differential	O
+sensitivity	O
+to	O
+DB	O
+,	O
+as	O
+measured	O
+by	O
+a	O
+lower	O
+concentration	O
+of	O
+DB	O
+which	O
+caused	O
+loss	O
+of	O
+righting	O
+in	O
+LS	O
+,	O
+was	O
+accompanied	O
+by	O
+an	O
+equal	O
+rate	O
+of	O
+water	O
+-	O
+soluble	O
+barbiturate	O
+brain	O
+distribution	O
+and	O
+elimination	O
+in	O
+the	O
+two	O
+lines	O
+.	O
+
+The	O
+existence	O
+of	O
+threshold	O
+concentrations	O
+,	O
+above	O
+which	O
+certain	O
+phenomena	O
+may	O
+occur	O
+,	O
+strengthens	O
+the	O
+role	O
+of	O
+sentinels	O
+.	O
+
+However	O
+,	O
+it	O
+was	O
+synthesized	O
+at	O
+both	O
+temperatures	O
+after	O
+addition	O
+of	O
+A23187	O
+.	O
+
+Ten	O
+out	O
+of	O
+10	O
+patients	O
+with	O
+progressive	O
+disease	O
+had	O
+mast	O
+cells	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+0	O
+.	O
+5	O
+%	O
+,	O
+hyaluronan	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+50	O
+micrograms	O
+.	O
+l	O
+-	O
+1	O
+and	O
+fibronectin	B-GENE
+greater	O
+than	O
+or	O
+equal	O
+to	O
+350	O
+micrograms	O
+.	O
+l	O
+-	O
+1	O
+compared	O
+to	O
+eight	O
+out	O
+of	O
+41	O
+patients	O
+with	O
+stable	O
+or	O
+regressive	O
+disease	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Our	O
+mapping	O
+results	O
+did	O
+not	O
+suggest	O
+involvement	O
+of	O
+this	O
+gene	O
+in	O
+previously	O
+mapped	O
+genetic	O
+disorders	O
+or	O
+in	O
+known	O
+neoplasia	O
+-	O
+associated	O
+translocation	O
+breakpoints	O
+.	O
+
+These	O
+changes	O
+weren	O
+'	O
+t	O
+so	O
+significant	O
+in	O
+the	O
+group	O
+of	O
+obese	O
+children	O
+who	O
+didn	O
+'	O
+t	O
+lose	O
+weight	O
+.	O
+
+Arsenic	O
+contents	O
+in	O
+native	O
+copper	O
+
+In	O
+ten	O
+other	O
+experiments	O
+(	O
+5	O
+experimental	O
+and	O
+5	O
+control	O
+rats	O
+)	O
+99mTc	O
+-	O
+sulfur	O
+colloid	O
+was	O
+injected	O
+intravenously	O
+.	O
+
+Magnetotherapy	O
+of	O
+hepatitis	O
+A	O
+and	O
+B	O
+in	O
+children	O
+
+These	O
+results	O
+were	O
+superior	O
+to	O
+those	O
+in	O
+24	O
+patients	O
+with	O
+conventional	O
+end	O
+-	O
+to	O
+-	O
+end	O
+sutures	O
+on	O
+clinical	O
+testing	O
+.	O
+
+Mutational	O
+analysis	O
+supports	O
+a	O
+role	O
+for	O
+multiple	O
+structural	O
+features	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+secretion	O
+signal	O
+of	O
+Escherichia	B-GENE
+coli	I-GENE
+haemolysin	I-GENE
+.	O
+
+Among	O
+blood	O
+donors	O
+in	O
+the	O
+Republic	O
+of	O
+Serbia	O
+,	O
+regardless	O
+the	O
+number	O
+of	O
+blood	O
+donations	O
+,	O
+the	O
+percentage	O
+of	O
+female	O
+donors	O
+is	O
+significantly	O
+lower	O
+compared	O
+to	O
+the	O
+percentage	O
+of	O
+male	O
+blood	O
+donors	O
+.	O
+
+Extramedullary	O
+relapse	O
+in	O
+childhood	O
+leukemia	O
+.	O
+
+Mycoplasma	O
+pneumoniae	O
+was	O
+isolated	O
+from	O
+the	O
+pleural	O
+fluid	O
+of	O
+this	O
+patient	O
+.	O
+
+RU486	O
+and	O
+ONO	O
+802	O
+in	O
+combination	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+effective	O
+in	O
+early	O
+termination	O
+of	O
+pregnancy	O
+.	O
+
+The	O
+presence	O
+of	O
+local	O
+abnormalities	O
+in	O
+both	O
+patients	O
+can	O
+support	O
+the	O
+hypothesis	O
+that	O
+the	O
+cortex	O
+,	O
+especially	O
+of	O
+the	O
+temporal	O
+anterior	O
+lobe	O
+,	O
+is	O
+involved	O
+in	O
+the	O
+origin	O
+of	O
+the	O
+laughing	O
+seizures	O
+.	O
+
+In	O
+line	O
+with	O
+the	O
+small	O
+values	O
+for	O
+QS	O
+/	O
+QC	O
+,	O
+our	O
+results	O
+further	O
+indicate	O
+that	O
+even	O
+large	O
+,	O
+well	O
+-	O
+perfused	O
+,	O
+occluded	O
+air	O
+spaces	O
+in	O
+the	O
+lung	O
+will	O
+hardly	O
+affect	O
+the	O
+recovered	O
+ventilation	O
+/	O
+perfusion	O
+distribution	O
+obtained	O
+from	O
+inert	O
+gas	O
+data	O
+when	O
+CDCSF6	O
+exceeds	O
+0	O
+.	O
+1	O
+ml	O
+.	O
+min	O
+-	O
+1	O
+.	O
+mmHg	O
+-	O
+1	O
+.	O
+
+Many	O
+cells	O
+were	O
+negative	O
+for	O
+endothelial	O
+-	O
+cell	O
+markers	O
+,	O
+and	O
+they	O
+reacted	O
+with	O
+a	O
+monoclonal	O
+antibody	O
+against	O
+muscle	O
+actin	B-GENE
+.	O
+
+CT	O
+abnormalities	O
+noted	O
+in	O
+term	O
+babies	O
+included	O
+hemorrhage	O
+(	O
+subarachnoid	O
+5	O
+.	O
+8	O
+%	O
+,	O
+intracerebral	O
+11	O
+.	O
+6	O
+%	O
+)	O
+,	O
+hypodensity	O
+(	O
+mild	O
+23	O
+.	O
+2	O
+%	O
+,	O
+moderate	O
+11	O
+.	O
+6	O
+%	O
+severe	O
+5	O
+.	O
+8	O
+%	O
+)	O
+;	O
+hypodensity	O
+with	O
+hemorrhage	O
+5	O
+.	O
+8	O
+%	O
+and	O
+cerebral	O
+atrophy	O
+5	O
+.	O
+8	O
+%	O
+.	O
+
+The	O
+effects	O
+of	O
+contrast	O
+media	O
+on	O
+coagulation	B-GENE
+factor	I-GENE
+XII	I-GENE
+.	O
+
+Pigs	O
+were	O
+switched	O
+from	O
+the	O
+growing	O
+to	O
+the	O
+finishing	O
+diet	O
+at	O
+57	O
+and	O
+61	O
+kg	O
+in	O
+Exp	O
+.	O
+
+In	O
+sixteen	O
+patients	O
+with	O
+moderate	O
+essential	O
+hypertension	O
+the	O
+effects	O
+of	O
+10	O
+-	O
+day	O
+nifedipine	O
+treatment	O
+on	O
+serum	O
+uric	O
+acid	O
+and	O
+renal	O
+excretion	O
+of	O
+uric	O
+acid	O
+were	O
+evaluated	O
+.	O
+
+TPTA	O
+produced	O
+brain	O
+congestion	O
+,	O
+and	O
+hepatic	O
+and	O
+pulmonary	O
+petechial	O
+and	O
+generalized	O
+hemorrhages	O
+.	O
+
+Examples	O
+are	O
+using	O
+more	O
+subjects	O
+or	O
+an	O
+improved	O
+research	O
+design	O
+,	O
+developing	O
+consensus	O
+statements	O
+or	O
+using	O
+meta	O
+-	O
+analysis	O
+.	O
+
+A	O
+two	O
+phase	O
+slug	O
+flow	O
+tubular	O
+heat	O
+exchanger	O
+was	O
+used	O
+for	O
+the	O
+thermal	O
+inactivation	O
+of	O
+Listeria	O
+monocytogenes	O
+in	O
+natural	O
+infected	O
+milk	O
+from	O
+seven	O
+cows	O
+.	O
+
+So	O
+far	O
+15	O
+children	O
+have	O
+been	O
+studied	O
+.	O
+
+Regional	O
+cerebral	O
+blood	O
+flow	O
+(	O
+rCBF	O
+)	O
+measurements	O
+and	O
+psychiatric	O
+ratings	O
+were	O
+performed	O
+on	O
+seven	O
+schizophrenic	O
+patients	O
+(	O
+mean	O
+age	O
+=	O
+41	O
+.	O
+4	O
+years	O
+)	O
+who	O
+had	O
+been	O
+examined	O
+18	O
+years	O
+previously	O
+in	O
+a	O
+study	O
+that	O
+used	O
+similar	O
+psychiatric	O
+ratings	O
+and	O
+a	O
+comparable	O
+rCBF	O
+technique	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+identified	O
+a	O
+strong	O
+positive	O
+cis	O
+-	O
+regulatory	O
+element	O
+at	O
+-	O
+70	O
+bp	O
+to	O
+-	O
+75	O
+bp	O
+in	O
+the	O
+LpS1	B-GENE
+beta	I-GENE
+promoter	I-GENE
+with	O
+the	O
+sequence	O
+(	O
+G	O
+)	O
+6	O
+and	O
+a	O
+similar	O
+,	O
+more	O
+distal	O
+cis	O
+-	O
+element	O
+at	O
+-	O
+721	O
+bp	O
+to	O
+-	O
+726	O
+bp	O
+.	O
+
+No	O
+case	O
+of	O
+SMF	O
+demonstrated	O
+expansive	O
+tumorous	O
+growth	O
+.	O
+
+Different	O
+doses	O
+of	O
+15	O
+-	O
+methyl	O
+-	O
+PGF2	O
+alpha	O
+(	O
+0	O
+.	O
+125	O
+-	O
+10	O
+mg	O
+)	O
+were	O
+used	O
+to	O
+induce	O
+luteolysis	O
+and	O
+oestrus	O
+in	O
+7	O
+heifers	O
+with	O
+28	O
+treatments	O
+on	O
+day	O
+8	O
+-	O
+12	O
+of	O
+the	O
+oestrous	O
+cycle	O
+.	O
+
+Review	O
+of	O
+the	O
+literature	O
+and	O
+report	O
+of	O
+a	O
+case	O
+of	O
+a	O
+dermoid	O
+cyst	O
+.	O
+
+Resolution	O
+of	O
+thermographic	O
+asymmetry	O
+and	O
+/	O
+or	O
+decrease	O
+in	O
+Delta	O
+T	O
+was	O
+demonstrated	O
+in	O
+approximately	O
+81	O
+%	O
+of	O
+the	O
+post	O
+-	O
+treatment	O
+population	O
+.	O
+
+Maize	B-GENE
+rbcS	I-GENE
+promoter	I-GENE
+activity	O
+depends	O
+on	O
+sequence	O
+elements	O
+not	O
+found	O
+in	O
+dicot	B-GENE
+rbcS	I-GENE
+promoters	I-GENE
+.	O
+
+Measurements	O
+were	O
+done	O
+with	O
+a	O
+commercial	O
+haematofluorometer	O
+Buchler	O
+ZF	O
+which	O
+was	O
+calibrated	O
+to	O
+the	O
+average	O
+haematocrit	O
+value	O
+of	O
+0	O
+.	O
+42	O
+.	O
+
+The	O
+relatively	O
+scanty	O
+number	O
+of	O
+examples	O
+,	O
+which	O
+could	O
+be	O
+justified	O
+by	O
+the	O
+variety	O
+and	O
+complexity	O
+of	O
+combined	O
+exposure	O
+,	O
+allows	O
+to	O
+conclude	O
+that	O
+life	O
+-	O
+style	O
+factors	O
+have	O
+considerable	O
+influence	O
+on	O
+interindividual	O
+differences	O
+in	O
+susceptibility	O
+to	O
+xenobiotics	O
+toxicity	O
+.	O
+
+The	O
+12S	B-GENE
+E1A	I-GENE
+product	I-GENE
+does	O
+not	O
+activate	O
+a	O
+TRE	O
+sequence	O
+,	O
+but	O
+cotransfection	O
+with	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+circumvents	O
+this	O
+lack	O
+of	O
+stimulation	O
+.	O
+
+After	O
+treatment	O
+with	O
+tunicamycin	O
+,	O
+the	O
+transfectants	O
+secreted	O
+unglycosylated	O
+18	O
+-	O
+kDa	O
+polypeptides	O
+which	O
+could	O
+also	O
+bind	O
+IgE	B-GENE
+.	O
+
+PAS1	B-GENE
+,	O
+a	O
+yeast	O
+gene	O
+required	O
+for	O
+peroxisome	O
+biogenesis	O
+,	O
+encodes	O
+a	O
+member	O
+of	O
+a	O
+novel	O
+family	O
+of	O
+putative	O
+ATPases	B-GENE
+.	O
+
+The	O
+pp90rsk	B-GENE
+-	I-GENE
+protein	I-GENE
+kinase	I-GENE
+activity	O
+(	O
+referred	O
+to	O
+as	O
+rsk	B-GENE
+-	I-GENE
+kinase	I-GENE
+)	O
+is	O
+also	O
+not	O
+related	O
+to	O
+cofactor	O
+-	O
+dependent	O
+signal	O
+transducing	O
+protein	O
+kinases	O
+such	O
+as	O
+the	O
+cyclic	B-GENE
+AMP	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinases	I-GENE
+,	O
+members	O
+of	O
+the	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+family	I-GENE
+,	O
+or	O
+other	O
+Ca2	B-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinases	I-GENE
+.	O
+
+Human	B-GENE
+GATA	I-GENE
+-	I-GENE
+3	I-GENE
+:	O
+a	O
+lineage	O
+-	O
+restricted	O
+transcription	O
+factor	O
+that	O
+regulates	O
+the	O
+expression	O
+of	O
+the	O
+T	B-GENE
+cell	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+gene	I-GENE
+.	O
+
+Like	O
+many	O
+eukaryotic	O
+transcription	O
+factors	O
+,	O
+these	O
+proteins	O
+bind	O
+to	O
+DNA	O
+as	O
+dimers	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+UvrA	B-GENE
+protein	I-GENE
+interacts	O
+with	O
+the	O
+UvrB	B-GENE
+protein	I-GENE
+to	O
+modulate	O
+its	O
+activities	O
+,	O
+both	O
+in	O
+solution	O
+and	O
+in	O
+association	O
+with	O
+DNA	O
+,	O
+where	O
+the	O
+UvrAB	B-GENE
+complex	I-GENE
+possesses	O
+a	O
+helicase	B-GENE
+activity	O
+.	O
+
+The	O
+ED30	O
+values	O
+were	O
+2	O
+.	O
+4	O
+and	O
+2	O
+.	O
+2	O
+mg	O
+/	O
+kg	O
+and	O
+similar	O
+to	O
+the	O
+respective	O
+values	O
+of	O
+nifedipine	O
+(	O
+ED	O
+30	O
+:	O
+2	O
+.	O
+4	O
+,	O
+2	O
+.	O
+1	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+Southwestern	O
+blot	O
+analysis	O
+demonstrated	O
+that	O
+this	O
+phosphoprotein	O
+can	O
+bind	O
+the	O
+kappa	B-GENE
+B	I-GENE
+element	I-GENE
+directly	O
+and	O
+specifically	O
+.	O
+
+The	O
+minus	O
+-	O
+end	O
+-	O
+directed	O
+microtubule	O
+motors	O
+,	O
+the	O
+dyneins	B-GENE
+,	O
+may	O
+also	O
+constitute	O
+a	O
+superfamily	O
+of	O
+force	O
+-	O
+generating	O
+proteins	O
+with	O
+distinct	O
+attachment	O
+domains	O
+.	O
+
+The	O
+incompatibility	O
+group	O
+W	O
+plasmid	O
+pSa	O
+suppresses	O
+Agrobacterium	O
+tumefaciens	O
+oncogenicity	O
+(	O
+J	O
+.	O
+
+Potential	O
+translational	O
+start	O
+signals	O
+are	O
+upstream	O
+of	O
+ORF1	O
+and	O
+ORF2	O
+.	O
+
+Imaging	O
+of	O
+D2	B-GENE
+dopamine	I-GENE
+receptor	I-GENE
+
+The	O
+abundance	O
+of	O
+transcripts	O
+from	O
+several	O
+unrelated	O
+genes	O
+is	O
+decreased	O
+in	O
+cdc68	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+cells	O
+after	O
+transfer	O
+to	O
+the	O
+restrictive	O
+temperature	O
+,	O
+while	O
+at	O
+least	O
+one	O
+transcript	O
+,	O
+from	O
+the	O
+HSP82	B-GENE
+gene	I-GENE
+,	O
+persists	O
+in	O
+an	O
+aberrant	O
+fashion	O
+.	O
+
+The	O
+murine	B-GENE
+Mov	I-GENE
+-	I-GENE
+34	I-GENE
+gene	I-GENE
+:	O
+full	O
+-	O
+length	O
+cDNA	O
+and	O
+genomic	O
+organization	O
+.	O
+
+CREB	B-GENE
+was	O
+identified	O
+as	O
+one	O
+of	O
+the	O
+protein	O
+components	O
+in	O
+several	O
+of	O
+the	O
+gel	O
+shift	O
+complexes	O
+formed	O
+with	O
+the	O
+variant	O
+CRE	O
+.	O
+
+The	O
+spectrum	O
+of	O
+histologically	O
+diagnosed	O
+malignant	O
+neoplasms	O
+in	O
+Sabah	O
+,	O
+1983	O
+-	O
+1988	O
+.	O
+
+When	O
+transfected	O
+into	O
+Drosophila	O
+SL	O
+-	O
+2	O
+cells	O
+,	O
+pCAT	O
+plasmid	O
+containing	O
+2	O
+,	O
+090	O
+bp	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+shows	O
+a	O
+3	O
+.	O
+0	O
+-	O
+to	O
+3	O
+.	O
+5	O
+-	O
+fold	O
+increase	O
+in	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+activity	O
+after	O
+induction	O
+with	O
+retinoic	O
+acid	O
+and	O
+/	O
+or	O
+8	O
+-	O
+bromo	O
+-	O
+cAMP	O
+.	O
+
+Two	O
+alternatively	O
+spliced	O
+5	O
+'	O
+UTRs	O
+,	O
+designated	O
+type	O
+I	O
+and	O
+type	O
+II	O
+,	O
+of	O
+222	O
+and	O
+115	O
+bp	O
+,	O
+respectively	O
+,	O
+were	O
+found	O
+associated	O
+with	O
+PFP	B-GENE
+.	O
+
+The	O
+N	O
+-	O
+terminus	O
+of	O
+another	O
+open	O
+reading	O
+frame	O
+was	O
+found	O
+3	O
+'	O
+from	O
+nifA	B-GENE
+and	O
+tentatively	O
+identified	O
+as	O
+nifB	B-GENE
+by	O
+amino	O
+acid	O
+sequence	O
+comparison	O
+.	O
+
+The	O
+RNA	O
+genome	O
+of	O
+rabbit	O
+hemorrhagic	O
+disease	O
+virus	O
+(	O
+RHDV	O
+)	O
+was	O
+molecularly	O
+cloned	O
+.	O
+
+Therefore	O
+,	O
+we	O
+have	O
+developed	O
+a	O
+system	O
+to	O
+study	O
+nuclear	O
+targeting	O
+in	O
+plants	O
+and	O
+have	O
+established	O
+that	O
+the	O
+nuclear	O
+transport	O
+machinery	O
+is	O
+similar	O
+in	O
+monocots	O
+and	O
+dicots	O
+.	O
+
+A	O
+novel	O
+cDNA	O
+clone	O
+termed	O
+R2	O
+was	O
+isolated	O
+by	O
+subtractive	O
+hybridization	O
+of	O
+a	O
+cDNA	O
+library	O
+of	O
+phytohemagglutinin	B-GENE
+(	O
+PHA	B-GENE
+)	O
+/	O
+phorbol	O
+myristate	O
+acetate	O
+-	O
+stimulated	O
+Jurkat	O
+cells	O
+and	O
+by	O
+rescreening	O
+a	O
+cDNA	O
+library	O
+of	O
+PHA	O
+-	O
+stimulated	O
+peripheral	O
+blood	O
+lymphocytes	O
+.	O
+
+Chagas	O
+'	O
+disease	O
+,	O
+visceral	O
+leishmaniasis	O
+,	O
+anti	B-GENE
+-	I-GENE
+nuclear	I-GENE
+factor	I-GENE
+,	O
+schistosomiasis	O
+,	O
+rheumatoid	B-GENE
+factor	I-GENE
+and	O
+normal	O
+controls	O
+.	O
+
+The	O
+second	O
+transcriptional	O
+unit	O
+,	O
+designated	O
+UL26	B-GENE
+.	I-GENE
+5	I-GENE
+,	O
+predicted	O
+to	O
+specify	O
+a	O
+protein	O
+of	O
+329	O
+amino	O
+acids	O
+,	O
+encodes	O
+the	O
+family	B-GENE
+35	I-GENE
+proteins	I-GENE
+;	O
+it	O
+is	O
+transcribed	O
+by	O
+an	O
+mRNA	O
+which	O
+initiates	O
+at	O
+approximately	O
+nucleotide	O
++	O
+1000	O
+of	O
+the	O
+UL26	B-GENE
+transcription	O
+initiation	O
+site	O
+and	O
+is	O
+translated	O
+from	O
+the	O
+methionine	O
+initiation	O
+codon	O
+located	O
+at	O
+position	O
++	O
+1099	O
+of	O
+the	O
+UL26	B-GENE
+transcriptional	I-GENE
+unit	I-GENE
+.	O
+
+The	O
+adeno	B-GENE
+-	I-GENE
+associated	I-GENE
+virus	I-GENE
+(	I-GENE
+AAV	I-GENE
+)	I-GENE
+rep	I-GENE
+gene	I-GENE
+encodes	O
+four	O
+proteins	O
+(	O
+Rep78	B-GENE
+,	O
+Rep68	B-GENE
+,	O
+Rep52	B-GENE
+,	O
+and	O
+Rep40	B-GENE
+)	O
+required	O
+for	O
+AAV	O
+DNA	O
+replication	O
+and	O
+AAV	O
+gene	O
+regulation	O
+.	O
+
+A	O
+larger	O
+region	O
+upstream	O
+of	O
+human	B-GENE
+CMV	I-GENE
+dbp	I-GENE
+also	O
+mediated	O
+replication	O
+in	O
+transient	O
+assays	O
+.	O
+
+It	O
+also	O
+contains	O
+a	O
+picornaviral	B-GENE
+3C	I-GENE
+-	I-GENE
+like	I-GENE
+protease	I-GENE
+domain	I-GENE
+and	O
+two	O
+papain	B-GENE
+-	I-GENE
+like	I-GENE
+protease	I-GENE
+domains	I-GENE
+.	O
+
+However	O
+,	O
+the	O
+relative	O
+positions	O
+of	O
+the	O
+VV	O
+genes	O
+(	O
+genus	O
+Orthopoxvirus	O
+)	O
+are	O
+different	O
+than	O
+those	O
+of	O
+the	O
+corresponding	O
+ORFs	O
+in	O
+SFV	O
+(	O
+genus	O
+Leporipoxvirus	O
+)	O
+,	O
+indicating	O
+complex	O
+rearrangements	O
+of	O
+DNA	O
+in	O
+the	O
+genome	O
+of	O
+one	O
+or	O
+both	O
+of	O
+these	O
+viruses	O
+subsequent	O
+to	O
+their	O
+divergence	O
+from	O
+a	O
+common	O
+ancestor	O
+.	O
+
+This	O
+result	O
+suggests	O
+that	O
+phosphorylation	O
+of	O
+Thr	O
+14	O
+and	O
+/	O
+or	O
+Tyr	O
+15	O
+inhibits	O
+p34cdc2	B-GENE
+kinase	I-GENE
+activity	O
+,	O
+in	O
+line	O
+with	O
+the	O
+location	O
+of	O
+these	O
+residues	O
+within	O
+the	O
+putative	O
+ATP	O
+binding	O
+site	O
+of	O
+the	O
+kinase	O
+.	O
+
+In	O
+short	O
+-	O
+term	O
+cotransfections	O
+,	O
+a	O
+pFRTK	B-GENE
+-	O
+CAT	B-GENE
+target	O
+containing	O
+EBNA	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+from	O
+the	O
+EBV	O
+origin	O
+of	O
+plasmid	O
+replication	O
+,	O
+ori	B-GENE
+-	I-GENE
+P	I-GENE
+,	O
+was	O
+transactivated	O
+by	O
+a	O
+carboxy	B-GENE
+-	I-GENE
+terminal	I-GENE
+EBNA	I-GENE
+-	I-GENE
+1	I-GENE
+construction	I-GENE
+(	O
+amino	O
+acids	O
+450	O
+to	O
+641	O
+)	O
+that	O
+also	O
+carried	O
+a	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+nuclear	I-GENE
+localization	I-GENE
+signal	I-GENE
+.	O
+
+The	O
+findings	O
+are	O
+compatible	O
+with	O
+the	O
+idea	O
+that	O
+the	O
+genes	O
+encoding	O
+PDGF	B-GENE
+receptors	I-GENE
+in	O
+glioma	O
+cells	O
+are	O
+regulated	O
+in	O
+concert	O
+with	O
+other	O
+genes	O
+,	O
+the	O
+expression	O
+of	O
+which	O
+may	O
+reflect	O
+the	O
+developmental	O
+program	O
+of	O
+normal	O
+glia	O
+cell	O
+lineages	O
+.	O
+
+Suggestive	O
+evidence	O
+was	O
+obtained	O
+that	O
+cstA	B-GENE
+is	O
+involved	O
+in	O
+peptide	O
+utilization	O
+.	O
+
+This	O
+study	O
+tested	O
+the	O
+hypothesis	O
+that	O
+sodium	O
+channel	O
+blocking	O
+drugs	O
+selectively	O
+prolong	O
+the	O
+late	O
+potential	O
+,	O
+or	O
+terminal	O
+low	O
+amplitude	O
+signal	O
+,	O
+portion	O
+of	O
+the	O
+signal	O
+-	O
+averaged	O
+QRS	O
+complex	O
+and	O
+that	O
+prolongation	O
+of	O
+the	O
+late	O
+potential	O
+would	O
+correlate	O
+with	O
+slowing	O
+of	O
+ventricular	O
+tachycardia	O
+.	O
+
+Identification	O
+and	O
+nucleotide	O
+sequence	O
+of	O
+Rhizobium	B-GENE
+meliloti	I-GENE
+insertion	I-GENE
+sequence	I-GENE
+ISRm3	I-GENE
+:	O
+similarity	O
+between	O
+the	O
+putative	O
+transposase	B-GENE
+encoded	O
+by	O
+ISRm3	B-GENE
+and	O
+those	O
+encoded	O
+by	O
+Staphylococcus	B-GENE
+aureus	I-GENE
+IS256	I-GENE
+and	O
+Thiobacillus	B-GENE
+ferrooxidans	I-GENE
+IST2	I-GENE
+.	O
+
+To	O
+determine	O
+the	O
+relationship	O
+of	O
+these	O
+viruses	O
+,	O
+the	O
+complete	O
+DNA	O
+sequence	O
+of	O
+KV	O
+consisting	O
+of	O
+4754	O
+bp	O
+was	O
+determined	O
+.	O
+
+Whereas	O
+a	O
+PR55	B-GENE
+beta	I-GENE
+transcript	I-GENE
+of	O
+about	O
+2	O
+.	O
+3	O
+kb	O
+was	O
+detected	O
+at	O
+high	O
+levels	O
+in	O
+the	O
+neuroblastoma	O
+derived	O
+cell	O
+line	O
+LA	O
+-	O
+N	O
+-	O
+1	O
+,	O
+the	O
+level	O
+of	O
+the	O
+mRNA	O
+was	O
+very	O
+low	O
+in	O
+the	O
+other	O
+human	O
+cell	O
+lines	O
+analyzed	O
+.	O
+
+Heterodimers	O
+of	O
+myogenin	B-GENE
+and	O
+E12	B-GENE
+(	O
+or	O
+MyoD	B-GENE
+and	O
+E12	B-GENE
+)	O
+specifically	O
+bound	O
+a	O
+restriction	O
+fragment	O
+extending	O
+from	O
+-	O
+200	O
+to	O
+-	O
+103	O
+relative	O
+to	O
+the	O
+start	O
+of	O
+cardiac	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+transcription	O
+.	O
+
+The	O
+effects	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+were	O
+further	O
+dissected	O
+by	O
+showing	O
+that	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+can	O
+inhibit	O
+differentiation	O
+independently	O
+of	O
+Id	B-GENE
+,	O
+a	O
+negative	O
+regulator	O
+of	O
+muscle	O
+differentiation	O
+.	O
+
+Stable	O
+association	O
+of	O
+U2	B-GENE
+snRNP	I-GENE
+with	O
+the	O
+branchpoint	O
+sequence	O
+of	O
+mammalian	O
+pre	O
+-	O
+mRNAs	O
+requires	O
+binding	O
+of	O
+a	O
+non	O
+-	O
+snRNP	O
+protein	O
+to	O
+the	O
+polypyrimidine	O
+tract	O
+.	O
+
+The	O
+Italian	O
+Lung	O
+Cancer	O
+Task	O
+Force	O
+(	O
+FONICAP	O
+)	O
+.	O
+
+The	O
+promoter	O
+activity	O
+of	O
+the	O
+gene	B-GENE
+encoding	I-GENE
+Alzheimer	I-GENE
+beta	I-GENE
+-	I-GENE
+amyloid	I-GENE
+precursor	I-GENE
+protein	I-GENE
+(	O
+APP	B-GENE
+)	O
+is	O
+regulated	O
+by	O
+two	O
+blocks	O
+of	O
+upstream	O
+sequences	O
+.	O
+
+This	O
+element	O
+was	O
+used	O
+to	O
+screen	O
+an	O
+EMBL3	O
+mouse	O
+genomic	O
+library	O
+.	O
+
+The	O
+MVV	O
+-	O
+value	O
+is	O
+under	O
+the	O
+predicted	O
+level	O
+in	O
+the	O
+case	O
+of	O
+67	O
+-	O
+76	O
+percent	O
+.	O
+
+The	O
+rad9	B-GENE
+.	I-GENE
+192	I-GENE
+DNA	I-GENE
+repair	I-GENE
+mutant	I-GENE
+from	I-GENE
+the	I-GENE
+fission	I-GENE
+yeast	I-GENE
+,	I-GENE
+Schizosaccharomyces	I-GENE
+pombe	I-GENE
+,	O
+is	O
+sensitive	O
+to	O
+both	O
+UV	O
+and	O
+ionising	O
+radiation	O
+.	O
+
+Review	O
+:	O
+deterioration	O
+of	O
+glucose	O
+tolerance	O
+with	O
+age	O
+:	O
+the	O
+role	O
+of	O
+insulin	B-GENE
+resistance	O
+.	O
+
+The	O
+5	O
+'	O
+region	O
+shows	O
+strong	O
+sequence	O
+similarity	O
+to	O
+Escherichia	O
+coli	O
+consensus	O
+promoters	O
+and	O
+ribosome	O
+-	O
+binding	O
+sequences	O
+and	O
+allows	O
+high	O
+levels	O
+of	O
+expression	O
+in	O
+E	O
+.	O
+coli	O
+.	O
+
+Premature	O
+initiation	O
+of	O
+mitosis	O
+in	O
+yeast	O
+lacking	O
+RCC1	B-GENE
+or	O
+an	O
+interacting	O
+GTPase	B-GENE
+.	O
+
+The	O
+method	O
+has	O
+been	O
+routinely	O
+used	O
+in	O
+our	O
+laboratory	O
+for	O
+1	O
+year	O
+and	O
+has	O
+proven	O
+to	O
+be	O
+a	O
+reliable	O
+procedure	O
+for	O
+the	O
+biological	O
+control	O
+of	O
+occupational	O
+exposure	O
+to	O
+toluene	O
+and	O
+/	O
+or	O
+xylene	O
+.	O
+
+The	O
+patient	O
+was	O
+a	O
+78	O
+-	O
+year	O
+-	O
+old	O
+male	O
+in	O
+whom	O
+skin	O
+lesions	O
+preceded	O
+the	O
+diagnosis	O
+of	O
+myelofibrosis	O
+.	O
+
+Oculus	O
+-	O
+500	O
+is	O
+a	O
+group	O
+of	O
+high	O
+resolution	O
+imaging	O
+boards	O
+for	O
+use	O
+with	O
+IBM	O
+-	O
+AT	O
+and	O
+compatible	O
+computers	O
+.	O
+
+After	O
+resection	O
+of	O
+the	O
+proximal	O
+fragment	O
+,	O
+all	O
+scaphoid	O
+contact	O
+area	O
+and	O
+pressure	O
+was	O
+born	O
+by	O
+the	O
+distal	O
+scaphoid	O
+fragment	O
+.	O
+
+Plate	O
+luting	O
+,	O
+a	O
+technique	O
+that	O
+uses	O
+polymethylmethacrylate	O
+(	O
+PMMA	O
+)	O
+interposed	O
+between	O
+the	O
+plate	O
+and	O
+the	O
+bone	O
+,	O
+as	O
+well	O
+as	O
+between	O
+the	O
+screw	O
+heads	O
+and	O
+the	O
+plate	O
+,	O
+to	O
+improve	O
+the	O
+stability	O
+of	O
+internal	O
+fixation	O
+was	O
+tested	O
+in	O
+vitro	O
+using	O
+20	O
+paired	O
+equine	O
+third	O
+metacarpal	O
+bones	O
+with	O
+mid	O
+-	O
+diaphyseal	O
+osteotomies	O
+plated	O
+with	O
+six	O
+-	O
+hole	O
+broad	O
+ASIF	O
+compression	O
+plates	O
+.	O
+
+These	O
+features	O
+were	O
+considered	O
+consistent	O
+with	O
+a	O
+diagnosis	O
+of	O
+Rothmund	O
+-	O
+Thomson	O
+syndrome	O
+.	O
+
+Thyroid	O
+lymphoma	O
+and	O
+its	O
+management	O
+.	O
+
+The	O
+protein	O
+encoded	O
+by	O
+ORF113	B-GENE
+contains	O
+a	O
+transmembrane	O
+domain	O
+.	O
+
+Space	O
+limitations	O
+prevent	O
+an	O
+exhaustive	O
+review	O
+of	O
+all	O
+biologic	O
+pharmaceuticals	O
+,	O
+such	O
+as	O
+tissue	B-GENE
+plasminogen	I-GENE
+activating	I-GENE
+substance	I-GENE
+,	O
+hormones	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+thyroid	O
+,	O
+insulin	B-GENE
+,	O
+growth	B-GENE
+hormone	I-GENE
+,	O
+erythropoietin	B-GENE
+)	O
+,	O
+clotting	O
+factors	O
+,	O
+and	O
+blood	O
+products	O
+.	O
+
+The	O
+various	O
+forms	O
+of	O
+sickle	O
+cell	O
+disease	O
+share	O
+the	O
+common	O
+feature	O
+of	O
+an	O
+abnormal	O
+globin	B-GENE
+chain	I-GENE
+that	O
+,	O
+under	O
+certain	O
+conditions	O
+such	O
+as	O
+hypoxia	O
+,	O
+results	O
+in	O
+the	O
+sickling	O
+of	O
+red	O
+blood	O
+cells	O
+and	O
+obstruction	O
+of	O
+blood	O
+vessels	O
+.	O
+
+The	O
+primary	O
+structure	O
+of	O
+each	O
+of	O
+the	O
+three	O
+proteins	O
+has	O
+about	O
+70	O
+%	O
+homology	O
+with	O
+that	O
+of	O
+mouse	B-GENE
+contrapsin	I-GENE
+,	O
+in	O
+contrast	O
+to	O
+43	O
+-	O
+46	O
+%	O
+homology	O
+with	O
+that	O
+of	O
+rat	B-GENE
+alpha	I-GENE
+1	I-GENE
+-	I-GENE
+protease	I-GENE
+inhibitor	O
+.	O
+
+Patterns	O
+of	O
+connections	O
+underlying	O
+cross	O
+-	O
+modality	O
+integration	O
+were	O
+studied	O
+by	O
+injecting	O
+distinguishable	O
+,	O
+retrograde	O
+tracers	O
+(	O
+Fluoro	O
+-	O
+Gold	O
+and	O
+diamidino	O
+yellow	O
+)	O
+in	O
+pairwise	O
+manner	O
+into	O
+different	O
+sensory	O
+representations	O
+(	O
+visual	O
+,	O
+somatosensory	O
+,	O
+and	O
+auditory	O
+)	O
+in	O
+the	O
+cerebral	O
+cortex	O
+of	O
+the	O
+rat	O
+.	O
+
+The	O
+across	O
+-	O
+fiber	O
+pattern	O
+of	O
+the	O
+responses	O
+to	O
+hypotonic	O
+NaCl	O
+solutions	O
+correlated	O
+strongly	O
+to	O
+that	O
+elicited	O
+by	O
+distilled	O
+H2O	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+400	O
+WORDS	O
+)	O
+
+Human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+IN	I-GENE
+,	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+,	O
+was	O
+purified	O
+to	O
+near	O
+homogeneity	O
+.	O
+
+Thigh	O
+girth	O
+correlated	O
+positively	O
+with	O
+HDL	B-GENE
+and	O
+HDL2	B-GENE
+-	I-GENE
+C	I-GENE
+and	O
+mass	O
+,	O
+and	O
+with	O
+LDL	B-GENE
+particle	O
+size	O
+among	O
+women	O
+.	O
+
+Contributions	O
+from	O
+pairs	O
+of	O
+source	O
+and	O
+target	O
+volume	O
+elements	O
+are	O
+summed	O
+for	O
+the	O
+S	O
+values	O
+between	O
+the	O
+tumor	O
+and	O
+itself	O
+,	O
+between	O
+the	O
+remaining	O
+healthy	O
+host	O
+organ	O
+and	O
+itself	O
+,	O
+and	O
+between	O
+the	O
+tumor	O
+and	O
+the	O
+remaining	O
+healthy	O
+host	O
+organ	O
+,	O
+with	O
+the	O
+reciprocity	O
+theorem	O
+assumed	O
+for	O
+the	O
+last	O
+.	O
+
+Tests	O
+showed	O
+that	O
+an	O
+overall	O
+impression	O
+of	O
+the	O
+force	O
+applied	O
+could	O
+be	O
+obtained	O
+from	O
+a	O
+laboratory	O
+simulation	O
+,	O
+but	O
+that	O
+clearing	O
+cement	O
+and	O
+testing	O
+cement	O
+were	O
+not	O
+modelled	O
+by	O
+this	O
+method	O
+.	O
+
+The	O
+cDNA	O
+contained	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+1392	O
+bp	O
+that	O
+predicted	O
+a	O
+protein	O
+of	O
+464	O
+amino	O
+acids	O
+and	O
+a	O
+molecular	O
+mass	O
+of	O
+52	O
+kDa	O
+;	O
+this	O
+protein	O
+has	O
+97	O
+%	O
+identity	O
+to	O
+rat	B-GENE
+liver	I-GENE
+glucokinase	I-GENE
+.	O
+
+Analysis	O
+of	O
+viral	O
+mutants	O
+in	O
+vivo	O
+demonstrated	O
+that	O
+the	O
+NFIII	B-GENE
+/	O
+OCT	B-GENE
+-	I-GENE
+1	I-GENE
+binding	O
+site	O
+and	O
+a	O
+conserved	O
+ATF	B-GENE
+motif	I-GENE
+were	O
+important	O
+for	O
+efficient	O
+viral	O
+growth	O
+.	O
+
+Recovery	O
+of	O
+radiolabelled	O
+BA	O
+through	O
+urine	O
+(	O
+28	O
+%	O
+)	O
+and	O
+faeces	O
+(	O
+22	O
+%	O
+)	O
+up	O
+to	O
+96	O
+hrs	O
+averaged	O
+50	O
+%	O
+,	O
+whereas	O
+residual	O
+radioactivity	O
+in	O
+liver	O
+and	O
+testis	O
+experienced	O
+a	O
+recovery	O
+of	O
+29	O
+%	O
+in	O
+scorbutic	O
+animals	O
+.	O
+
+Paradoxically	O
+,	O
+however	O
+,	O
+the	O
+GH	B-GENE
+receptor	I-GENE
+cloned	O
+from	O
+liver	O
+exhibits	O
+no	O
+sequence	O
+similarity	O
+to	O
+receptors	O
+with	O
+known	O
+signal	O
+transduction	O
+mechanisms	O
+,	O
+including	O
+those	O
+exhibiting	O
+ligand	O
+-	O
+activated	O
+tyrosine	B-GENE
+kinase	I-GENE
+activity	O
+.	O
+
+This	O
+indicates	O
+that	O
+under	O
+certain	O
+experimental	O
+conditions	O
+cdc2	B-GENE
+/	O
+p58	B-GENE
+and	O
+cdc2	B-GENE
+/	O
+p62	B-GENE
+may	O
+express	O
+some	O
+differences	O
+in	O
+their	O
+catalytic	O
+activity	O
+.	O
+
+Mutation	O
+analysis	O
+implicated	O
+multiple	O
+segments	O
+of	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+as	O
+contributing	O
+to	O
+the	O
+inhibitory	O
+effect	O
+.	O
+
+Identification	O
+of	O
+Ets	B-GENE
+-	O
+and	O
+notch	B-GENE
+-	O
+related	O
+subunits	O
+in	O
+GA	B-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+enzymatic	O
+response	O
+of	O
+neutrophils	O
+and	O
+monocytes	O
+was	O
+similar	O
+although	O
+the	O
+magnitude	O
+of	O
+the	O
+NADPH	B-GENE
+oxidase	I-GENE
+activity	O
+was	O
+significantly	O
+higher	O
+in	O
+neutrophils	O
+than	O
+in	O
+monocytes	O
+.	O
+
+In	O
+the	O
+ileum	O
+,	O
+enterotoxin	O
+increased	O
+the	O
+luminal	O
+disappearance	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+peripheral	O
+blood	O
+appearance	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+of	O
+chloroquine	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+attention	O
+to	O
+these	O
+issues	O
+can	O
+substantially	O
+improve	O
+the	O
+quality	O
+of	O
+research	O
+on	O
+AIDS	O
+related	O
+behaviors	O
+on	O
+Black	O
+communities	O
+.	O
+
+The	O
+effectiveness	O
+of	O
+alpha	O
+-	O
+mercapto	O
+-	O
+beta	O
+-	O
+(	O
+2	O
+-	O
+furyl	O
+)	O
+acrylic	O
+acid	O
+(	O
+MFA	O
+)	O
+and	O
+N	O
+-	O
+benzyl	O
+-	O
+N	O
+-	O
+dithiocarboxy	O
+-	O
+D	O
+-	O
+glucamine	O
+(	O
+NaB	O
+)	O
+,	O
+used	O
+in	O
+combination	O
+,	O
+in	O
+the	O
+mobilization	O
+and	O
+excretion	O
+of	O
+lead	O
+was	O
+investigated	O
+in	O
+rats	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+beta	B-GENE
+-	I-GENE
+1	I-GENE
+may	O
+act	O
+as	O
+a	O
+tissue	O
+-	O
+specific	O
+,	O
+trans	O
+-	O
+acting	O
+regulator	O
+of	O
+the	O
+expression	O
+of	O
+the	O
+beta	B-GENE
+-	I-GENE
+zein	I-GENE
+gene	I-GENE
+in	O
+developing	O
+maize	O
+endosperm	O
+.	O
+
+This	O
+study	O
+examines	O
+the	O
+effects	O
+of	O
+hypovolemia	O
+on	O
+the	O
+extracellular	O
+ptO2	O
+and	O
+ptH	O
+distributions	O
+at	O
+multiple	O
+tissue	O
+sites	O
+using	O
+a	O
+recently	O
+developed	O
+multipoint	O
+microelectrode	O
+,	O
+that	O
+provides	O
+simultaneous	O
+measurements	O
+of	O
+ptO2	O
+and	O
+ptH	O
+.	O
+
+All	O
+members	O
+are	O
+also	O
+capable	O
+of	O
+activating	O
+in	O
+vivo	O
+transcription	O
+from	O
+promoters	O
+that	O
+contain	O
+a	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+.	O
+
+The	O
+domains	O
+involved	O
+in	O
+superactivation	O
+appear	O
+to	O
+be	O
+a	O
+subset	O
+of	O
+those	O
+necessary	O
+to	O
+achieve	O
+synergistic	O
+activation	O
+.	O
+
+Information	O
+on	O
+conserved	O
+noncoding	O
+sequences	O
+will	O
+help	O
+in	O
+studies	O
+on	O
+the	O
+regulation	O
+of	O
+the	O
+pro	B-GENE
+alpha	I-GENE
+1	I-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+collagen	I-GENE
+gene	I-GENE
+.	O
+
+Chlamydia	O
+trachomatis	O
+and	O
+Chlamydia	O
+psittaci	O
+were	O
+not	O
+affected	O
+by	O
+methanol	O
+fixation	O
+.	O
+
+Although	O
+human	O
+infections	O
+with	O
+bacteraemia	O
+due	O
+to	O
+Pasteurella	O
+multocida	O
+are	O
+not	O
+uncommon	O
+,	O
+endocarditis	O
+associated	O
+with	O
+P	O
+.	O
+haemolytica	O
+is	O
+rare	O
+.	O
+
+For	O
+SMX	O
+at	O
+pH	O
+7	O
+.	O
+0	O
+,	O
+a	O
+1	O
+:	O
+1	O
+complex	O
+is	O
+formed	O
+,	O
+but	O
+at	O
+pH	O
+7	O
+.	O
+5	O
+HPCD	O
+has	O
+little	O
+effect	O
+on	O
+the	O
+solubility	O
+of	O
+the	O
+highly	O
+ionized	O
+SMX	O
+,	O
+presumably	O
+since	O
+only	O
+un	O
+-	O
+ionized	O
+molecules	O
+can	O
+form	O
+inclusion	O
+complexes	O
+with	O
+the	O
+HPCD	O
+.	O
+
+PO2	O
+measurements	O
+using	O
+a	O
+double	O
+barrelled	O
+recess	O
+type	O
+microelectrodes	O
+were	O
+measured	O
+in	O
+the	O
+optic	O
+nerve	O
+head	O
+of	O
+miniature	O
+pigs	O
+in	O
+normoxia	O
+and	O
+hyperoxia	O
+.	O
+
+POU	B-GENE
+-	O
+specific	O
+and	O
+POU	B-GENE
+-	O
+homeo	O
+domains	O
+of	O
+Oct3	B-GENE
+were	O
+produced	O
+in	O
+Echerichia	O
+coli	O
+for	O
+characterization	O
+of	O
+DNA	O
+binding	O
+to	O
+the	O
+octamer	O
+sequence	O
+.	O
+
+The	O
+nucleotide	O
+(	O
+nt	O
+)	O
+sequences	O
+of	O
+the	O
+exons	O
+,	O
+exon	O
+/	O
+intron	O
+boundaries	O
+and	O
+5	O
+'	O
+-	O
+and	O
+3	O
+'	O
+-	O
+untranslated	O
+regions	O
+were	O
+determined	O
+.	O
+
+Out	O
+of	O
+40	O
+patients	O
+,	O
+who	O
+initially	O
+did	O
+not	O
+show	O
+eye	O
+complications	O
+due	O
+to	O
+leprosy	O
+,	O
+37	O
+patients	O
+were	O
+essentially	O
+the	O
+same	O
+10	O
+years	O
+later	O
+.	O
+
+Thus	O
+,	O
+two	O
+very	O
+different	O
+regulatory	O
+elements	O
+are	O
+used	O
+to	O
+mediate	O
+estrogen	O
+induction	O
+of	O
+related	O
+genes	O
+in	O
+chickens	O
+and	O
+amphibians	O
+.	O
+
+Experimentally	O
+in	O
+green	O
+monkeys	O
+,	O
+Syrian	O
+hamsters	O
+and	O
+white	O
+mice	O
+the	O
+authors	O
+studied	O
+the	O
+pathogenic	O
+properties	O
+of	O
+a	O
+new	O
+virus	O
+Issyk	O
+-	O
+Kul	O
+.	O
+
+Increasing	O
+mean	O
+arterial	O
+pressure	O
+by	O
+phenylephrine	O
+infusion	O
+to	O
+levels	O
+much	O
+greater	O
+than	O
+produced	O
+by	O
+NMA	O
+and	O
+NNA	O
+caused	O
+only	O
+small	O
+reductions	O
+in	O
+cardiac	O
+output	O
+.	O
+
+J	O
+.	O
+
+With	O
+stepwise	O
+reductions	O
+in	O
+flow	O
+,	O
+the	O
+peak	O
+(	O
+S	O
+)	O
+and	O
+trough	O
+(	O
+D	O
+)	O
+points	O
+of	O
+the	O
+maximum	O
+shifted	O
+-	O
+frequency	O
+envelope	O
+fell	O
+in	O
+parallel	O
+in	O
+a	O
+linear	O
+fashion	O
+until	O
+D	O
+reached	O
+zero	O
+.	O
+
+The	O
+IE0	B-GENE
+gene	I-GENE
+product	O
+also	O
+transactivated	O
+the	O
+IE1	B-GENE
+promoter	I-GENE
+but	O
+did	O
+not	O
+affect	O
+expression	O
+from	O
+its	O
+own	O
+promoter	O
+.	O
+
+Evaluation	O
+of	O
+left	O
+ventricular	O
+function	O
+using	O
+gated	O
+planar	O
+myocardial	O
+imaging	O
+with	O
+Tc	O
+-	O
+99m	O
+-	O
+MIBI	O
+
+Bone	O
+marrow	O
+abnormalities	O
+in	O
+Hodgkin	O
+'	O
+s	O
+disease	O
+are	O
+reviewed	O
+and	O
+the	O
+current	O
+understanding	O
+of	O
+the	O
+pathological	O
+mechanisms	O
+leading	O
+to	O
+aplastic	O
+anemia	O
+is	O
+discussed	O
+.	O
+
+The	O
+smaller	O
+uptake	O
+rate	O
+and	O
+faster	O
+clearance	O
+rate	O
+resulted	O
+in	O
+the	O
+lower	O
+BCF	O
+for	O
+SWA	O
+killifish	O
+.	O
+
+Increases	O
+in	O
+the	O
+perfusate	O
+PCO2	O
+but	O
+not	O
+in	O
+the	O
+perfusate	O
+H	O
++	O
+were	O
+highly	O
+correlated	O
+with	O
+decreases	O
+in	O
+both	O
+myocardial	O
+contractility	O
+and	O
+oxygen	O
+consumption	O
+(	O
+r2	O
+=	O
+.	O
+88	O
+)	O
+.	O
+
+Expression	O
+was	O
+cell	O
+cycle	O
+controlled	O
+,	O
+with	O
+steady	O
+-	O
+state	O
+RNA	O
+levels	O
+significantly	O
+higher	O
+in	O
+growth	O
+-	O
+arrested	O
+than	O
+in	O
+growth	O
+-	O
+stimulated	O
+cells	O
+.	O
+
+Determinants	O
+of	O
+recurrent	O
+ischaemia	O
+and	O
+revascularisation	O
+procedures	O
+after	O
+thrombolysis	O
+with	O
+recombinant	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+in	O
+primary	O
+coronary	O
+occlusion	O
+.	O
+
+Therefore	O
+,	O
+the	O
+rbcL	B-GENE
+-	O
+rbcS	B-GENE
+locus	O
+seems	O
+to	O
+be	O
+barely	O
+expressed	O
+under	O
+a	O
+standard	O
+condition	O
+for	O
+photoautotrophic	O
+growth	O
+.	O
+
+Relationship	O
+between	O
+mitochondrial	B-GENE
+NADH	I-GENE
+-	I-GENE
+ubiquinone	I-GENE
+reductase	I-GENE
+and	O
+a	O
+bacterial	B-GENE
+NAD	I-GENE
+-	I-GENE
+reducing	I-GENE
+hydrogenase	I-GENE
+.	O
+
+Analysis	O
+of	O
+mRNA	O
+expression	O
+shows	O
+that	O
+AT	B-GENE
+-	I-GENE
+BP1	I-GENE
+and	O
+AT	B-GENE
+-	I-GENE
+BP2	I-GENE
+are	O
+expressed	O
+in	O
+all	O
+the	O
+tissues	O
+examined	O
+.	O
+
+3	O
+cases	O
+
+Sequence	O
+requirements	O
+for	O
+premature	O
+transcription	O
+arrest	O
+within	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+mouse	B-GENE
+c	I-GENE
+-	I-GENE
+fos	I-GENE
+gene	I-GENE
+.	O
+
+Infarct	O
+regional	O
+ejection	O
+fraction	O
+improved	O
+by	O
+10	O
+.	O
+1	O
++	O
+/	O
+-	O
+2	O
+.	O
+1	O
+%	O
+between	O
+early	O
+and	O
+late	O
+studies	O
+when	O
+the	O
+infarct	O
+-	O
+related	O
+artery	O
+was	O
+patent	O
+and	O
+by	O
+4	O
+.	O
+8	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+%	O
+if	O
+it	O
+was	O
+occluded	O
+(	O
+p	O
+=	O
+0	O
+.	O
+048	O
+)	O
+;	O
+changes	O
+in	O
+global	O
+and	O
+noninfarct	O
+regional	O
+ejection	O
+fraction	O
+were	O
+similar	O
+irrespective	O
+of	O
+perfusion	O
+status	O
+.	O
+
+One	O
+of	O
+its	O
+lysine	O
+residues	O
+is	O
+modified	O
+by	O
+spermidine	O
+to	O
+form	O
+hypusine	O
+,	O
+a	O
+posttranslational	O
+modification	O
+unique	O
+to	O
+eIF	B-GENE
+-	I-GENE
+5A	I-GENE
+.	O
+
+The	O
+plasmid	O
+shuffle	O
+technique	O
+was	O
+used	O
+to	O
+replace	O
+the	O
+wild	O
+-	O
+type	O
+gene	O
+with	O
+the	O
+mutant	O
+form	O
+,	O
+resulting	O
+in	O
+failure	O
+of	O
+the	O
+yeast	O
+cells	O
+to	O
+grow	O
+.	O
+
+If	O
+this	O
+is	O
+the	O
+case	O
+,	O
+identification	O
+and	O
+characterization	O
+of	O
+transcripts	O
+from	O
+the	O
+Ig	B-GENE
+loci	I-GENE
+should	O
+permit	O
+a	O
+better	O
+understanding	O
+of	O
+the	O
+gene	O
+rearrangement	O
+process	O
+.	O
+
+Transcription	O
+of	O
+the	O
+metH	B-GENE
+gene	I-GENE
+in	I-GENE
+Salmonella	I-GENE
+typhimurium	I-GENE
+and	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+is	O
+positively	O
+regulated	O
+by	O
+the	O
+metR	B-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+a	O
+DNA	O
+binding	O
+protein	O
+.	O
+
+Disruption	O
+of	O
+the	O
+chromosomal	B-GENE
+AAR1	I-GENE
+gene	I-GENE
+in	O
+alpha	O
+and	O
+a	O
+/	O
+alpha	O
+cells	O
+conferred	O
+the	O
+nonmating	O
+phenotype	O
+,	O
+and	O
+the	O
+a	O
+/	O
+alpha	O
+diploids	O
+could	O
+not	O
+sporulate	O
+.	O
+
+The	O
+effect	O
+of	O
+ICRF	O
+-	O
+187	O
+on	O
+the	O
+antitumor	O
+response	O
+induced	O
+by	O
+the	O
+combination	O
+of	O
+ADR	O
+and	O
+WBH	O
+was	O
+also	O
+investigated	O
+in	O
+order	O
+to	O
+assess	O
+alterations	O
+in	O
+the	O
+therapeutic	O
+index	O
+of	O
+this	O
+combined	O
+therapeutic	O
+modality	O
+treatment	O
+.	O
+
+The	O
+ORF	O
+was	O
+analyzed	O
+for	O
+secondary	O
+structural	O
+features	O
+,	O
+and	O
+the	O
+sequence	O
+data	O
+bases	O
+were	O
+searched	O
+for	O
+homologies	O
+.	O
+
+Mitomycin	O
+-	O
+C	O
+can	O
+cause	O
+severe	O
+necrosis	O
+and	O
+ulceration	O
+when	O
+extravasated	O
+inadvertently	O
+into	O
+skin	O
+and	O
+soft	O
+tissues	O
+following	O
+IV	O
+drug	O
+administration	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+have	O
+cloned	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+nidogen	I-GENE
+gene	I-GENE
+.	O
+
+Consistent	O
+with	O
+the	O
+in	O
+vivo	O
+result	O
+,	O
+the	O
+pseudorevertant	O
+endonucleases	O
+in	O
+the	O
+crude	O
+cell	O
+extract	O
+display	O
+site	O
+-	O
+specific	O
+partial	O
+DNA	O
+cleavage	O
+activity	O
+.	O
+
+Additionally	O
+,	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+beta	I-GENE
+,	O
+but	O
+not	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+,	O
+also	O
+prevented	O
+the	O
+binding	O
+of	O
+Rel	B-GENE
+to	O
+the	O
+kappa	B-GENE
+B	I-GENE
+site	I-GENE
+.	O
+
+Sequence	O
+analysis	O
+reveals	O
+that	O
+the	O
+DNA	O
+binding	O
+domain	O
+of	O
+ILF	B-GENE
+has	O
+strong	O
+homology	O
+to	O
+the	O
+recently	O
+described	O
+fork	B-GENE
+head	I-GENE
+DNA	I-GENE
+binding	I-GENE
+domain	I-GENE
+found	O
+in	O
+the	O
+Drosophila	B-GENE
+homeotic	I-GENE
+protein	I-GENE
+fork	I-GENE
+head	I-GENE
+and	O
+a	O
+family	O
+of	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factors	I-GENE
+,	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+.	O
+
+Lengthy	O
+and	O
+repeated	O
+hemodialyses	O
+were	O
+required	O
+to	O
+lower	O
+lithemia	O
+to	O
+nontoxic	O
+ranges	O
+.	O
+
+A	O
+single	O
+i	O
+.	O
+p	O
+.	O
+injection	O
+of	O
+d	O
+,	O
+l	O
+-	O
+baclofen	O
+10	O
+mg	O
+/	O
+kg	O
+both	O
+reduced	O
+noradrenaline	O
+(	O
+NA	O
+)	O
+biosynthesis	O
+in	O
+vivo	O
+(	O
+31	O
+%	O
+)	O
+and	O
+the	O
+endogenous	O
+concentration	O
+of	O
+normetanephrine	O
+(	O
+NMN	O
+)	O
+(	O
+32	O
+%	O
+)	O
+and	O
+increased	O
+NA	O
+levels	O
+(	O
+28	O
+%	O
+)	O
+.	O
+
+Fufang	O
+wuzi	O
+yanzong	O
+pills	O
+have	O
+strong	O
+leukogenic	O
+effect	O
+on	O
+cyclophosphamide	O
+induced	O
+leukopenia	O
+in	O
+mice	O
+.	O
+
+Mutations	O
+in	O
+the	O
+small	O
+subunit	O
+of	O
+ribulosebisphosphate	B-GENE
+carboxylase	I-GENE
+affect	O
+subunit	O
+binding	O
+and	O
+catalysis	O
+.	O
+
+The	O
+structural	O
+changes	O
+in	O
+intra	O
+-	O
+acinar	O
+artery	O
+manifested	O
+mainly	O
+by	O
+an	O
+increase	O
+in	O
+number	O
+of	O
+muscular	O
+artery	O
+resulting	O
+from	O
+muscularization	O
+of	O
+precursor	O
+cells	O
+(	O
+pericytes	O
+and	O
+intermediate	O
+cells	O
+)	O
+located	O
+within	O
+partially	O
+muscular	O
+and	O
+nonmuscular	O
+arterial	O
+wall	O
+to	O
+smooth	O
+muscle	O
+cell	O
+,	O
+and	O
+by	O
+the	O
+medial	O
+wall	O
+thickened	O
+due	O
+to	O
+hypertrophy	O
+and	O
+hyperplasia	O
+of	O
+smooth	O
+muscle	O
+cells	O
+as	O
+well	O
+as	O
+accumulation	O
+of	O
+a	O
+large	O
+amount	O
+of	O
+collagen	B-GENE
+,	O
+especially	O
+the	O
+type	B-GENE
+1	I-GENE
+collagen	I-GENE
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+NZ	O
+-	O
+107	O
+may	O
+be	O
+a	O
+useful	O
+drug	O
+for	O
+the	O
+treatment	O
+of	O
+bronchial	O
+asthma	O
+by	O
+reducing	O
+late	O
+-	O
+phase	O
+airway	O
+responses	O
+and	O
+airway	O
+hyperreactivity	O
+.	O
+
+In	O
+study	O
+2	O
+,	O
+the	O
+correlation	O
+coefficients	O
+between	O
+the	O
+ISO2	O
+measurements	O
+obtained	O
+at	O
+the	O
+ulcer	O
+margin	O
+and	O
+at	O
+the	O
+adjacent	O
+normal	O
+mucosa	O
+,	O
+and	O
+delta	O
+ISO2	O
+obtained	O
+by	O
+the	O
+experienced	O
+observer	O
+and	O
+one	O
+of	O
+the	O
+three	O
+learners	O
+were	O
+0	O
+.	O
+94	O
+,	O
+0	O
+.	O
+97	O
+,	O
+and	O
+0	O
+.	O
+94	O
+,	O
+respectively	O
+.	O
+
+Bronchial	O
+mucosa	O
+tattooing	O
+in	O
+persons	O
+exposed	O
+to	O
+different	O
+industrial	O
+aerosols	O
+did	O
+not	O
+depend	O
+on	O
+the	O
+forms	O
+of	O
+PC	O
+,	O
+DB	O
+and	O
+the	O
+diseases	O
+'	O
+stages	O
+.	O
+
+Anti	B-GENE
+-	I-GENE
+HBc	I-GENE
+production	O
+of	O
+PBMC	O
+was	O
+enhanced	O
+remarkably	O
+in	O
+this	O
+case	O
+.	O
+
+Lipoprotein	B-GENE
+lipase	I-GENE
+(	O
+LPL	B-GENE
+)	O
+,	O
+a	O
+key	O
+enzyme	O
+in	O
+normal	O
+lipoprotein	O
+metabolism	O
+,	O
+has	O
+a	O
+complex	O
+pattern	O
+of	O
+regulation	O
+and	O
+tissue	O
+-	O
+specific	O
+expression	O
+.	O
+
+Deletion	O
+of	O
+the	O
+proximal	O
+octanucleotide	O
+motif	O
+from	O
+the	O
+plasmid	O
+containing	O
+the	O
+-	O
+461	O
+fragment	O
+of	O
+the	O
+LPL	B-GENE
+promoter	I-GENE
+,	O
+resulted	O
+in	O
+a	O
+79	O
+and	O
+76	O
+%	O
+decrease	O
+in	O
+the	O
+level	O
+of	O
+expression	O
+in	O
+transfected	O
+3T3	O
+-	O
+L1	O
+adipocytes	O
+and	O
+HepG2	O
+hepatocytes	O
+,	O
+respectively	O
+.	O
+
+We	O
+examined	O
+the	O
+binding	O
+of	O
+purified	O
+T3	B-GENE
+receptor	I-GENE
+alpha	I-GENE
+(	O
+T3R	B-GENE
+alpha	I-GENE
+)	O
+,	O
+overexpressed	O
+in	O
+Escherichia	O
+coli	O
+,	O
+to	O
+wild	O
+-	O
+type	O
+and	O
+up	O
+and	O
+down	O
+mutations	O
+of	O
+the	O
+rGH	B-GENE
+T3RE	B-GENE
+to	O
+evaluate	O
+whether	O
+transcriptional	O
+potency	O
+correlates	O
+with	O
+changes	O
+in	O
+T3R	B-GENE
+binding	O
+.	O
+
+Comparison	O
+of	O
+the	O
+cDNA	O
+-	O
+predicted	O
+avian	B-GENE
+TnIcardiac	I-GENE
+amino	I-GENE
+acid	I-GENE
+sequences	I-GENE
+with	O
+known	O
+TnI	B-GENE
+sequences	I-GENE
+indicated	O
+1	O
+)	O
+that	O
+the	O
+presence	O
+of	O
+an	O
+N	O
+-	O
+terminal	O
+extension	O
+sequence	O
+carrying	O
+a	O
+dual	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+phosphorylation	O
+target	O
+site	O
+and	O
+an	O
+adjacent	O
+proline	O
+-	O
+rich	O
+segment	O
+is	O
+an	O
+ancient	O
+cardiac	O
+-	O
+specific	O
+feature	O
+of	O
+TnI	B-GENE
+which	O
+has	O
+been	O
+conserved	O
+since	O
+the	O
+bird	O
+/	O
+mammal	O
+divergence	O
+,	O
+2	O
+)	O
+that	O
+features	O
+of	O
+the	O
+near	O
+-	O
+N	O
+-	O
+terminal	O
+troponin	B-GENE
+C	I-GENE
+(	O
+TnC	B-GENE
+)	O
+-	O
+binding	O
+site	O
+sequence	O
+suggest	O
+isoform	O
+-	O
+specific	O
+adaptation	O
+of	O
+TnI	B-GENE
+and	O
+TnC	B-GENE
+,	O
+and	O
+3	O
+)	O
+that	O
+the	O
+avian	O
+TnIcardiac	B-GENE
+internal	O
+actin	B-GENE
+/	I-GENE
+TnC	I-GENE
+-	I-GENE
+binding	I-GENE
+,	I-GENE
+actomyosin	I-GENE
+-	I-GENE
+inhibitory	I-GENE
+,	I-GENE
+domain	I-GENE
+shows	O
+significant	O
+sequence	O
+divergence	O
+from	O
+mammalian	B-GENE
+TnIcardiac	I-GENE
+sequences	I-GENE
+,	O
+including	O
+the	O
+absence	O
+of	O
+a	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+target	O
+site	O
+which	O
+is	O
+a	O
+cardiac	O
+-	O
+specific	O
+feature	O
+of	O
+TnI	B-GENE
+in	O
+mammals	O
+.	O
+
+Ventilatory	O
+management	O
+casebook	O
+.	O
+
+An	O
+ASSEMBLER	O
+routine	O
+for	O
+on	O
+-	O
+line	O
+graphic	O
+display	O
+and	O
+averaging	O
+of	O
+data	O
+acquired	O
+on	O
+a	O
+personal	O
+microcomputer	O
+.	O
+
+Expression	O
+of	O
+the	O
+mouse	B-GENE
+TSH	I-GENE
+beta	I-GENE
+gene	I-GENE
+,	O
+therefore	O
+,	O
+gives	O
+rise	O
+to	O
+multiple	O
+mRNAs	O
+,	O
+each	O
+with	O
+a	O
+unique	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+the	O
+ROSP	O
+undergoes	O
+a	O
+number	O
+of	O
+fluctuations	O
+in	O
+the	O
+negative	O
+and	O
+positive	O
+directions	O
+with	O
+a	O
+gradually	O
+decreasing	O
+amplitude	O
+in	O
+the	O
+course	O
+of	O
+5	O
+-	O
+25	O
+days	O
+following	O
+the	O
+operation	O
+,	O
+after	O
+which	O
+relatively	O
+stable	O
+negative	O
+values	O
+of	O
+the	O
+ROSP	O
+are	O
+established	O
+on	O
+the	O
+average	O
+in	O
+electrodes	O
+implanted	O
+to	O
+the	O
+level	O
+of	O
+the	O
+dura	O
+mater	O
+,	O
+and	O
+positive	O
+values	O
+in	O
+electrodes	O
+implanted	O
+to	O
+the	O
+level	O
+of	O
+the	O
+pia	O
+mater	O
+.	O
+
+Blood	O
+flow	O
+velocity	O
+waveforms	O
+were	O
+recorded	O
+by	O
+pulsed	O
+Doppler	O
+examination	O
+of	O
+the	O
+fetal	O
+internal	O
+carotid	O
+and	O
+middle	O
+cerebral	O
+arteries	O
+using	O
+the	O
+established	O
+transabdominal	O
+route	O
+as	O
+well	O
+as	O
+a	O
+new	O
+transvaginal	O
+approach	O
+.	O
+
+Quantitative	O
+analysis	O
+of	O
+DNA	O
+using	O
+flow	O
+cytometry	O
+and	O
+immunocytochemical	O
+findings	O
+in	O
+16	O
+cases	O
+of	O
+cardiac	O
+myxomas	O
+
+Sequence	O
+analysis	O
+revealed	O
+that	O
+in	O
+addition	O
+to	O
+the	O
+non	O
+-	O
+spliced	O
+variant	O
+,	O
+multiple	O
+mRNA	O
+species	O
+were	O
+generated	O
+by	O
+alternative	O
+splicing	O
+resulting	O
+in	O
+the	O
+exclusion	O
+of	O
+92	O
+,	O
+166	O
+,	O
+170	O
+,	O
+174	O
+and	O
+263	O
+nucleotides	O
+(	O
+nt	O
+)	O
+,	O
+respectively	O
+,	O
+from	O
+exon	O
+1	O
+.	O
+
+Position	O
+22	O
+is	O
+an	O
+isoleucine	O
+in	O
+the	O
+complete	B-GENE
+SsoL12	I-GENE
+protein	I-GENE
+sequence	I-GENE
+,	O
+coded	O
+by	O
+an	O
+AUA	O
+codon	O
+.	O
+
+Symptoms	O
+due	O
+to	O
+the	O
+action	O
+of	O
+mastocyte	O
+mediators	O
+were	O
+observed	O
+.	O
+
+In	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+copper	O
+levels	O
+exert	O
+some	O
+control	O
+over	O
+the	O
+level	O
+of	O
+SOD1	B-GENE
+expression	O
+.	O
+
+Of	O
+these	O
+179	O
+samples	O
+,	O
+Mobiluncus	O
+SP	O
+was	O
+observed	O
+in	O
+35	O
+(	O
+19	O
+.	O
+6	O
+%	O
+)	O
+using	O
+Gram	O
+staining	O
+and	O
+in	O
+18	O
+(	O
+10	O
+.	O
+1	O
+%	O
+)	O
+this	O
+microorganism	O
+was	O
+isolated	O
+in	O
+agar	O
+RLK	O
+and	O
+anaerobic	O
+atmosphere	O
+.	O
+
+Previous	O
+investigators	O
+have	O
+suggested	O
+that	O
+subretinal	O
+blood	O
+damages	O
+the	O
+retina	O
+in	O
+part	O
+because	O
+of	O
+its	O
+solid	O
+fibrin	B-GENE
+meshwork	O
+.	O
+
+Twenty	O
+-	O
+four	O
+hours	O
+later	O
+,	O
+the	O
+animals	O
+were	O
+randomized	O
+to	O
+subretinal	O
+treatment	O
+with	O
+2	O
+.	O
+5	O
+micrograms	O
+of	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+or	O
+a	O
+similar	O
+volume	O
+of	O
+physiologic	O
+saline	O
+.	O
+
+Neuro	O
+-	O
+otological	O
+examinations	O
+revealed	O
+spontaneous	O
+downbeat	O
+nystagmus	O
+,	O
+bilateral	O
+gaze	O
+nystagmus	O
+and	O
+rebound	O
+nystagmus	O
+.	O
+
+Since	O
+the	O
+morphology	O
+of	O
+the	O
+lesions	O
+can	O
+mimic	O
+that	O
+of	O
+other	O
+cutaneous	O
+disorders	O
+,	O
+Bowen	O
+'	O
+s	O
+disease	O
+is	O
+often	O
+not	O
+recognized	O
+initially	O
+.	O
+
+Equine	O
+amnion	O
+and	O
+live	O
+yeast	O
+cell	O
+derivative	O
+were	O
+evaluated	O
+as	O
+a	O
+biological	O
+dressing	O
+and	O
+as	O
+a	O
+topical	O
+wound	O
+medicament	O
+respectively	O
+,	O
+in	O
+the	O
+treatment	O
+of	O
+granulating	O
+wounds	O
+of	O
+the	O
+distal	O
+portion	O
+of	O
+the	O
+limbs	O
+of	O
+horses	O
+.	O
+
+To	O
+lower	O
+the	O
+current	O
+high	O
+incidence	O
+of	O
+NANB	O
+-	O
+induced	O
+PTH	O
+,	O
+in	O
+1986	O
+,	O
+the	O
+American	O
+Association	O
+of	O
+Blood	O
+Banks	O
+(	O
+AABB	O
+)	O
+recommended	O
+testing	O
+for	O
+these	O
+PTH	O
+-	O
+associated	O
+"	O
+surrogate	O
+"	O
+markers	O
+on	O
+all	O
+donated	O
+units	O
+of	O
+blood	O
+.	O
+
+Fusion	O
+of	O
+ubiquitin	B-GENE
+to	O
+pADPRP	B-GENE
+increased	O
+the	O
+yield	O
+of	O
+pADPRP	B-GENE
+approximately	O
+10	O
+-	O
+fold	O
+compared	O
+to	O
+that	O
+of	O
+the	O
+unfused	O
+enzyme	O
+.	O
+
+In	O
+group	O
+III	O
+,	O
+patients	O
+also	O
+received	O
+their	O
+own	O
+mediastinal	O
+drainage	O
+blood	O
+,	O
+shed	O
+for	O
+6	O
+hours	O
+after	O
+operation	O
+,	O
+after	O
+concentration	O
+and	O
+washing	O
+in	O
+a	O
+MBRS	O
+.	O
+
+The	O
+effect	O
+of	O
+salmon	B-GENE
+calcitonin	I-GENE
+nasal	O
+spray	O
+in	O
+women	O
+with	O
+established	O
+osteoporosis	O
+has	O
+also	O
+been	O
+studied	O
+.	O
+
+Skeletal	O
+muscle	O
+metaboreceptor	O
+responses	O
+are	O
+impaired	O
+in	O
+heart	O
+failure	O
+.	O
+
+Skeletal	O
+muscle	O
+metaboreceptor	O
+exercise	O
+responses	O
+are	O
+attenuated	O
+in	O
+heart	O
+failure	O
+.	O
+
+Evaluation	O
+of	O
+antiepileptic	O
+drug	O
+effect	O
+on	O
+membrane	O
+fluidity	O
+.	O
+
+The	O
+examinations	O
+were	O
+performed	O
+on	O
+two	O
+groups	O
+of	O
+20	O
+(	O
+using	O
+AmF	O
+/	O
+SnF2	O
+)	O
+-	O
+,	O
+resp	O
+.	O
+
+The	O
+vaccine	O
+used	O
+was	O
+known	O
+to	O
+be	O
+immunogenic	O
+for	O
+older	O
+children	O
+and	O
+adults	O
+.	O
+
+Both	O
+groups	O
+then	O
+underwent	O
+hypnotic	O
+induction	O
+,	O
+and	O
+completed	O
+the	O
+test	O
+again	O
+(	O
+R2	O
+)	O
+.	O
+
+Applications	O
+of	O
+three	O
+-	O
+dimensional	O
+analysis	O
+to	O
+the	O
+auditory	O
+P300	O
+.	O
+
+The	O
+construct	O
+was	O
+introduced	O
+into	O
+BW2001	O
+(	O
+xth	O
+-	O
+11	O
+,	O
+nfo	O
+-	O
+2	O
+)	O
+strain	O
+cells	O
+of	O
+Escherichia	O
+coli	O
+.	O
+
+Recombinant	B-GENE
+human	I-GENE
+TFIID	I-GENE
+supported	O
+weak	O
+basal	O
+transcription	O
+in	O
+heat	O
+-	O
+treated	O
+nuclear	O
+extracts	O
+whereas	O
+a	O
+partially	O
+purified	O
+TFIID	B-GENE
+fraction	O
+from	O
+HeLa	O
+cells	O
+reconstituted	O
+a	O
+maximal	O
+level	O
+of	O
+transcription	O
+.	O
+
+Only	O
+after	O
+a	O
+pretreatment	O
+aimed	O
+at	O
+increasing	O
+its	O
+oxide	O
+surface	O
+layer	O
+was	O
+titanium	O
+powder	O
+found	O
+to	O
+accelerate	O
+the	O
+precipitation	O
+from	O
+solutions	O
+containing	O
+2	O
+mmol	O
+/	O
+L	O
+CaCl2	O
+,	O
+2	O
+mmol	O
+/	O
+L	O
+KH2PO4	O
+,	O
+50	O
+mmol	O
+/	O
+L	O
+Hepes	O
+,	O
+pH	O
+7	O
+.	O
+2	O
+,	O
+and	O
+to	O
+induce	O
+precipitation	O
+from	O
+metastable	O
+solutions	O
+containing	O
+1	O
+.	O
+2	O
+mmol	O
+/	O
+L	O
+CaCl2	O
+,	O
+1	O
+.	O
+2	O
+mmol	O
+/	O
+L	O
+KH2PO4	O
+,	O
+50	O
+mmol	O
+/	O
+L	O
+Hepes	O
+,	O
+pH	O
+7	O
+.	O
+2	O
+,	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+We	O
+conclude	O
+that	O
+solidification	O
+could	O
+occur	O
+in	O
+all	O
+feeds	O
+containing	O
+casein	B-GENE
+and	O
+that	O
+alternative	O
+feeds	O
+should	O
+be	O
+considered	O
+in	O
+patients	O
+with	O
+increased	O
+gastric	O
+acidity	O
+.	O
+
+Neither	O
+model	O
+,	O
+as	O
+applied	O
+,	O
+provided	O
+a	O
+satisfactory	O
+account	O
+of	O
+the	O
+effects	O
+of	O
+the	O
+main	O
+variables	O
+of	O
+number	O
+of	O
+tones	O
+and	O
+amount	O
+of	O
+perturbation	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+400	O
+WORDS	O
+)	O
+
+Determination	O
+of	O
+an	O
+RNA	O
+structure	O
+involved	O
+in	O
+splicing	O
+inhibition	O
+of	O
+a	O
+muscle	O
+-	O
+specific	O
+exon	O
+.	O
+
+Endothelial	O
+cells	O
+stored	O
+with	O
+University	O
+of	O
+Wisconsin	O
+solution	O
+excluded	O
+trypan	O
+blue	O
+better	O
+(	O
+1	O
+.	O
+0	O
+%	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+%	O
+cells	O
+stained	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+.	O
+
+The	O
+effect	O
+of	O
+diffusion	O
+limitation	O
+was	O
+quantified	O
+in	O
+terms	O
+of	O
+the	O
+ratio	O
+O2	O
+uptake	O
+/	O
+O2	O
+requirement	O
+(	O
+=	O
+fraction	O
+of	O
+cross	O
+-	O
+sectional	O
+area	O
+supplied	O
+with	O
+O2	O
+)	O
+,	O
+assuming	O
+local	O
+O2	O
+requirement	O
+per	O
+unit	O
+volume	O
+to	O
+be	O
+constant	O
+and	O
+independent	O
+of	O
+PO2	O
+at	O
+PO2	O
+greater	O
+than	O
+0	O
+.	O
+
+(	O
+2	O
+)	O
+Diffusion	O
+limitation	O
+in	O
+the	O
+heterogeneous	O
+model	O
+sets	O
+in	O
+at	O
+a	O
+lower	O
+O2	O
+requirement	O
+value	O
+,	O
+and	O
+increases	O
+more	O
+gradually	O
+with	O
+increasing	O
+O2	O
+requirement	O
+,	O
+than	O
+in	O
+the	O
+corresponding	O
+homogeneous	O
+models	O
+with	O
+the	O
+same	O
+average	O
+cylinder	O
+diameter	O
+.	O
+
+The	O
+antihypertensive	O
+effect	O
+of	O
+Estulic	O
+has	O
+been	O
+examined	O
+over	O
+a	O
+12	O
+-	O
+month	O
+period	O
+in	O
+101	O
+hypertensive	O
+patients	O
+.	O
+
+At	O
+the	O
+time	O
+of	O
+the	O
+seizure	O
+,	O
+the	O
+patient	O
+was	O
+asked	O
+to	O
+read	O
+a	O
+test	O
+phrase	O
+aloud	O
+until	O
+it	O
+was	O
+read	O
+correctly	O
+and	O
+clearly	O
+.	O
+
+Monitoring	O
+patients	O
+with	O
+acute	O
+leukemia	O
+for	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+TNF	B-GENE
+levels	O
+throughout	O
+the	O
+clinical	O
+course	O
+of	O
+disease	O
+may	O
+help	O
+clarify	O
+the	O
+causes	O
+of	O
+febrile	O
+episodes	O
+.	O
+
+Echinococcus	O
+granulosus	O
+was	O
+diagnosed	O
+by	O
+fine	O
+-	O
+needle	O
+aspiration	O
+cytology	O
+of	O
+a	O
+lung	O
+cyst	O
+in	O
+a	O
+6	O
+-	O
+yr	O
+-	O
+old	O
+white	O
+female	O
+in	O
+central	O
+Missouri	O
+.	O
+
+The	O
+sequence	O
+was	O
+determined	O
+of	O
+6493	O
+nucleotides	O
+encompassing	O
+the	O
+bet	B-GENE
+genes	I-GENE
+of	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+which	O
+encode	O
+the	O
+osmoregulatory	O
+choline	O
+-	O
+glycine	O
+betaine	O
+pathway	O
+.	O
+
+A	O
+7	O
+-	O
+day	O
+treatment	O
+of	O
+amphotericin	O
+B	O
+(	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+i	O
+.	O
+p	O
+.	O
+)	O
+significantly	O
+reduced	O
+the	O
+glomerular	O
+filtration	O
+rate	O
+(	O
+GFR	O
+)	O
+measured	O
+as	O
+inuline	O
+clearance	O
+and	O
+creatinine	O
+clearance	O
+(	O
+0	O
+.	O
+74	O
++	O
+/	O
+-	O
+0	O
+.	O
+29	O
+and	O
+0	O
+.	O
+16	O
++	O
+/	O
+-	O
+0	O
+.	O
+04	O
+ml	O
+/	O
+min	O
+,	O
+respectively	O
+)	O
+in	O
+comparison	O
+to	O
+vehicle	O
+-	O
+treated	O
+rats	O
+(	O
+2	O
+.	O
+04	O
++	O
+/	O
+-	O
+0	O
+.	O
+23	O
+and	O
+1	O
+.	O
+29	O
++	O
+/	O
+-	O
+0	O
+.	O
+19	O
+ml	O
+/	O
+min	O
+,	O
+respectively	O
+)	O
+.	O
+
+Confocal	O
+fluorescence	O
+microscopy	O
+in	O
+modern	O
+cell	O
+biology	O
+.	O
+
+Toluene	O
+is	O
+the	O
+chemical	O
+most	O
+frequently	O
+present	O
+in	O
+cases	O
+involving	O
+volatile	O
+solvents	O
+.	O
+
+Fortunately	O
+DDT	O
+-	O
+,	O
+HCH	O
+-	O
+and	O
+HCB	O
+-	O
+levels	O
+decreased	O
+in	O
+breast	O
+milk	O
+during	O
+the	O
+last	O
+years	O
+.	O
+
+A	O
+herpesvirus	O
+proteinase	O
+activity	O
+has	O
+been	O
+identified	O
+and	O
+partially	O
+characterized	O
+by	O
+using	O
+the	O
+cloned	O
+enzyme	O
+and	O
+substrate	O
+genes	O
+in	O
+transient	O
+transfection	O
+assays	O
+.	O
+
+Adult	O
+H	O
+,	O
+but	O
+not	O
+R	O
+,	O
+manifested	O
+the	O
+burrowing	O
+preference	O
+whenever	O
+offered	O
+the	O
+opportunity	O
+.	O
+
+The	O
+rear	O
+silver	O
+liquid	O
+chamber	O
+was	O
+threefold	O
+thick	O
+to	O
+17	O
+MeV	O
+protons	O
+in	O
+water	O
+and	O
+it	O
+efficiently	O
+produced	O
+either	O
+13N	O
+by	O
+the	O
+16O	O
+(	O
+p	O
+,	O
+alpha	O
+)	O
+13N	O
+reaction	O
+or	O
+[	O
+18F	O
+]	O
+fluoride	O
+ion	O
+by	O
+the	O
+18O	O
+(	O
+p	O
+,	O
+n	O
+)	O
+18F	O
+reaction	O
+.	O
+
+Heterogeneous	O
+electron	O
+transfer	O
+of	O
+cytochrome	B-GENE
+c	I-GENE
+facilitated	O
+by	O
+polypyrrole	O
+and	O
+methylene	O
+blue	O
+polypyrrole	O
+film	O
+modified	O
+electrodes	O
+.	O
+
+Selective	O
+activation	O
+of	O
+adrenaline	O
+secretion	O
+by	O
+the	O
+rat	O
+adrenal	O
+in	O
+neuroglycopenia	O
+detected	O
+via	O
+microdialysis	O
+
+The	O
+1489	O
+-	O
+base	O
+pair	O
+EFIA	B-GENE
+cDNA	O
+encodes	O
+a	O
+322	O
+-	O
+amino	O
+acid	O
+protein	O
+which	O
+is	O
+nearly	O
+identical	O
+to	O
+two	O
+previously	O
+described	O
+human	O
+DNA	O
+binding	O
+proteins	O
+.	O
+
+Four	O
+putative	O
+positive	O
+cDNA	O
+clones	O
+were	O
+isolated	O
+,	O
+and	O
+the	O
+largest	O
+insert	O
+(	O
+pASB	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+was	O
+sequenced	O
+in	O
+both	O
+orientations	O
+.	O
+
+Sci	O
+.	O
+
+Dose	O
+standardisation	O
+of	O
+botulinum	B-GENE
+toxin	I-GENE
+.	O
+
+The	O
+coding	O
+sequence	O
+for	O
+a	O
+260	O
+-	O
+amino	O
+-	O
+acid	O
+residue	O
+polypeptide	O
+was	O
+interrupted	O
+by	O
+a	O
+single	O
+short	O
+intron	O
+of	O
+60	O
+base	O
+pairs	O
+(	O
+bp	O
+)	O
+,	O
+and	O
+about	O
+70	O
+%	O
+of	O
+the	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+Drosophila	B-GENE
+PCNA	I-GENE
+was	O
+identical	O
+to	O
+the	O
+rat	O
+and	O
+human	B-GENE
+PCNA	I-GENE
+polypeptides	I-GENE
+,	O
+with	O
+conserved	O
+unique	O
+repeats	O
+of	O
+leucine	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+.	O
+
+Translational	O
+fusions	O
+of	O
+the	O
+aroF	B-GENE
+regulatory	I-GENE
+regions	I-GENE
+to	O
+lacZ	B-GENE
+were	O
+constructed	O
+and	O
+then	O
+introduced	O
+in	O
+single	O
+copy	O
+into	O
+the	O
+E	O
+.	O
+coli	O
+chromosome	O
+.	O
+beta	B-GENE
+-	I-GENE
+Galactosidase	I-GENE
+assays	O
+for	O
+tyrR	O
+-	O
+mediated	O
+regulation	O
+of	O
+aroF	B-GENE
+-	O
+lacZ	B-GENE
+expression	O
+revealed	O
+that	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+TyrR	I-GENE
+repressor	I-GENE
+apparently	O
+recognizes	O
+the	O
+operators	O
+of	O
+both	O
+organisms	O
+with	O
+about	O
+equal	O
+efficiency	O
+.	O
+
+During	O
+exercise	O
+K	O
++	O
+is	O
+released	O
+from	O
+contracting	O
+muscle	O
+and	O
+plasma	O
+K	O
++	O
+concentration	O
+rises	O
+.	O
+
+Following	O
+treatment	O
+,	O
+serum	O
+estradiol	O
+levels	O
+were	O
+higher	O
+in	O
+groups	O
+E	O
++	O
+T	O
+and	O
+E	O
+than	O
+in	O
+group	O
+C	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+beta	O
+-	O
+adrenergic	O
+agonist	O
+,	O
+isoproterenol	O
+,	O
+has	O
+little	O
+influence	O
+on	O
+vascular	O
+capacitance	O
+or	O
+liver	O
+volume	O
+of	O
+dogs	O
+,	O
+unless	O
+the	O
+hepatic	O
+outflow	O
+resistance	O
+is	O
+elevated	O
+by	O
+agents	O
+such	O
+as	O
+histamine	O
+.	O
+
+DNA	O
+sequence	O
+and	O
+evolution	O
+of	O
+the	O
+CPS	B-GENE
+domain	I-GENE
+of	O
+the	O
+Syrian	B-GENE
+hamster	I-GENE
+multifunctional	I-GENE
+protein	I-GENE
+CAD	I-GENE
+.	O
+
+A	O
+high	O
+-	O
+frequency	O
+restriction	O
+fragment	O
+length	O
+polymorphism	O
+was	O
+evident	O
+in	O
+the	O
+DNA	O
+from	O
+29	O
+unrelated	O
+individuals	O
+using	O
+the	O
+enzyme	O
+BglII	B-GENE
+.	O
+
+The	O
+antilog	O
+transformation	O
+of	O
+pH	O
+did	O
+not	O
+improve	O
+the	O
+results	O
+.	O
+
+Telomeres	O
+prevent	O
+end	O
+-	O
+to	O
+-	O
+end	O
+fusions	O
+and	O
+exonucleolytic	O
+degradation	O
+,	O
+enable	O
+the	O
+end	O
+of	O
+the	O
+linear	O
+DNA	O
+molecule	O
+to	O
+replicate	O
+,	O
+and	O
+function	O
+in	O
+cell	O
+division	O
+.	O
+
+One	O
+of	O
+these	O
+is	O
+located	O
+in	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+,	O
+and	O
+may	O
+encode	O
+regulatory	O
+sequences	O
+.	O
+
+The	O
+native	O
+enzyme	O
+purified	O
+from	O
+protease	B-GENE
+-	I-GENE
+B	I-GENE
+-	O
+deficient	O
+URA2	B-GENE
+-	O
+transformed	O
+cells	O
+,	O
+was	O
+phosphorylated	O
+in	O
+vitro	O
+using	O
+catalytic	O
+subunits	O
+of	O
+pure	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+.	O
+
+A	O
+bovine	O
+abomasum	O
+lambda	O
+gt11	O
+cDNA	O
+library	O
+was	O
+screened	O
+with	O
+a	O
+monoclonal	O
+antibody	O
+raised	O
+against	O
+the	O
+rabbit	B-GENE
+H	I-GENE
+,	I-GENE
+K	I-GENE
+-	I-GENE
+ATPase	I-GENE
+beta	I-GENE
+subunit	I-GENE
+.	O
+
+Judicious	O
+use	O
+of	O
+laboratory	O
+testing	O
+,	O
+including	O
+monitoring	O
+of	O
+CD4	B-GENE
+cell	O
+counts	O
+,	O
+is	O
+recommended	O
+.	O
+
+There	O
+is	O
+no	O
+TATA	O
+box	O
+appropriately	O
+spaced	O
+upstream	O
+from	O
+the	O
+transcription	O
+initiation	O
+site	O
+.	O
+
+Characterization	O
+of	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+growth	O
+-	O
+regulated	O
+Syrian	B-GENE
+hamster	I-GENE
+CAD	I-GENE
+gene	I-GENE
+.	O
+
+Early	O
+cirrhosis	O
+,	O
+an	O
+early	O
+modality	O
+of	O
+the	O
+evolution	O
+of	O
+acute	O
+hepatitis	O
+.	O
+
+Combined	O
+therapy	O
+with	O
+MK	O
+-	O
+801	O
+and	O
+nimodipine	O
+for	O
+protection	O
+of	O
+ischemic	O
+brain	O
+damage	O
+.	O
+
+Initial	O
+screening	O
+of	O
+a	O
+rat	O
+liver	O
+cDNA	O
+library	O
+with	O
+an	O
+oligonucleotide	O
+probe	O
+derived	O
+from	O
+the	O
+rat	O
+SCP2	B-GENE
+protein	O
+sequence	O
+revealed	O
+an	O
+825	O
+-	O
+base	O
+pair	O
+cDNA	O
+clone	O
+coding	O
+for	O
+the	O
+complete	O
+SCP2	B-GENE
+protein	O
+sequence	O
+.	O
+
+Cloning	O
+,	O
+expression	O
+,	O
+and	O
+nucleotide	O
+sequence	O
+of	O
+rat	B-GENE
+liver	I-GENE
+sterol	I-GENE
+carrier	I-GENE
+protein	I-GENE
+2	I-GENE
+cDNAs	I-GENE
+.	O
+
+The	O
+addition	O
+of	O
+an	O
+equimolar	O
+complex	O
+of	O
+the	O
+fourth	O
+and	O
+seventh	O
+largest	O
+subunits	O
+,	O
+purified	O
+from	O
+pol	B-GENE
+II	I-GENE
+holoenzyme	I-GENE
+by	O
+ion	O
+-	O
+exchange	O
+chromatography	O
+in	O
+the	O
+presence	O
+of	O
+urea	O
+,	O
+restored	O
+promoter	O
+-	O
+directed	O
+initiation	O
+activity	O
+to	O
+pol	B-GENE
+II	I-GENE
+delta	I-GENE
+4	I-GENE
+/	I-GENE
+7	I-GENE
+.	O
+
+We	O
+report	O
+here	O
+the	O
+identification	O
+of	O
+HSF	B-GENE
+in	O
+the	O
+fission	O
+yeast	O
+Schizosaccharomyces	O
+pombe	O
+.	O
+
+Induction	O
+requires	O
+the	O
+ACE1	B-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+which	O
+binds	O
+to	O
+specific	O
+sites	O
+in	O
+the	O
+promoter	O
+region	O
+of	O
+the	O
+CUP1	B-GENE
+gene	I-GENE
+.	O
+
+Gel	O
+mobility	O
+shift	O
+assays	O
+using	O
+a	O
+synthetic	O
+E6	B-GENE
+motif	I-GENE
+detected	O
+a	O
+B	O
+-	O
+cell	O
+-	O
+specific	O
+complex	O
+in	O
+addition	O
+to	O
+a	O
+ubiquitous	O
+band	O
+found	O
+also	O
+in	O
+T	O
+cells	O
+and	O
+HeLa	O
+cells	O
+.	O
+
+The	O
+sequence	O
+of	O
+four	O
+clones	O
+was	O
+sufficient	O
+to	O
+construct	O
+a	O
+3018	B-GENE
+-	I-GENE
+bp	I-GENE
+BAL	I-GENE
+cDNA	I-GENE
+structure	O
+.	O
+
+The	O
+application	O
+of	O
+these	O
+instruments	O
+allows	O
+occlusion	O
+of	O
+the	O
+ascending	O
+aorta	O
+traversed	O
+by	O
+the	O
+perfusion	O
+cannula	O
+inserted	O
+directly	O
+or	O
+through	O
+the	O
+apex	O
+of	O
+the	O
+heart	O
+as	O
+well	O
+as	O
+simultaneous	O
+left	O
+ventricular	O
+venting	O
+.	O
+
+Adenylosuccinate	B-GENE
+synthetase	I-GENE
+(	O
+IMP	O
+:	O
+L	B-GENE
+-	I-GENE
+aspartate	I-GENE
+ligase	I-GENE
+(	O
+GDP	O
+)	O
+,	O
+EC	B-GENE
+6	I-GENE
+.	I-GENE
+3	I-GENE
+.	I-GENE
+4	I-GENE
+.	I-GENE
+4	I-GENE
+)	O
+plays	O
+an	O
+important	O
+role	O
+in	O
+purine	O
+biosynthesis	O
+catalyzing	O
+the	O
+GTP	O
+-	O
+dependent	O
+conversion	O
+of	O
+IMP	O
+to	O
+AMP	O
+.	O
+
+Immunophenotyping	O
+in	O
+four	O
+cases	O
+,	O
+demonstrated	O
+non	O
+-	O
+B	O
+,	O
+non	O
+-	O
+T	O
+cell	O
+origin	O
+in	O
+three	O
+and	O
+pre	O
+-	O
+B	O
+cell	O
+origin	O
+in	O
+one	O
+.	O
+
+The	O
+results	O
+strengthen	O
+the	O
+conclusion	O
+that	O
+predominantly	O
+dynamic	O
+activity	O
+increases	O
+the	O
+G4	B-GENE
+content	O
+of	O
+mature	O
+innervated	O
+fast	O
+muscles	O
+.	O
+
+We	O
+reviewed	O
+the	O
+records	O
+of	O
+151	O
+patients	O
+with	O
+optic	O
+neuritis	O
+examined	O
+over	O
+an	O
+eight	O
+-	O
+year	O
+period	O
+.	O
+
+Cut	O
+-	O
+off	O
+levels	O
+that	O
+define	O
+abnormality	O
+are	O
+rather	O
+arbitrary	O
+and	O
+this	O
+decreases	O
+the	O
+specificity	O
+of	O
+the	O
+test	O
+in	O
+apparently	O
+healthy	O
+patients	O
+.	O
+
+Alanine	B-GENE
+aminotransferase	I-GENE
+in	O
+clinical	O
+practice	O
+.	O
+
+Nucleotide	O
+sequence	O
+analysis	O
+of	O
+the	O
+Pseudomonas	B-GENE
+putida	I-GENE
+PpG7	I-GENE
+salicylate	I-GENE
+hydroxylase	I-GENE
+gene	I-GENE
+(	O
+nahG	B-GENE
+)	O
+and	O
+its	O
+3	O
+'	O
+-	O
+flanking	O
+region	O
+.	O
+
+All	O
+six	O
+ARF	B-GENE
+cDNAs	I-GENE
+are	O
+more	O
+similar	O
+to	O
+each	O
+other	O
+than	O
+to	O
+other	O
+approximately	O
+20	B-GENE
+-	I-GENE
+kDa	I-GENE
+guanine	I-GENE
+nucleotide	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+.	O
+
+The	O
+long	O
+terminal	O
+repeat	O
+(	O
+LTR	O
+)	O
+of	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+(	O
+HIV	O
+)	O
+contains	O
+three	O
+binding	O
+sites	O
+for	O
+the	O
+transcriptional	O
+factor	O
+Sp1	B-GENE
+.	O
+
+DNA	O
+from	O
+PCR	O
+was	O
+labeled	O
+and	O
+used	O
+to	O
+isolate	O
+several	O
+lambda	O
+gt11	O
+cDNA	O
+clones	O
+,	O
+including	O
+one	O
+full	O
+-	O
+length	O
+one	O
+(	O
+Dd	B-GENE
+kinase	I-GENE
+-	I-GENE
+2	I-GENE
+)	O
+.	O
+
+A	O
+.	O
+
+Perilunar	O
+luxation	O
+-	O
+-	O
+an	O
+unusual	O
+injury	O
+demanding	O
+immediate	O
+and	O
+correct	O
+treatment	O
+
+Landsberg	O
+(	O
+La	O
+-	O
+O	O
+)	O
+and	O
+cv	O
+.	O
+
+In	O
+summary	O
+,	O
+at	O
+equianesthetic	O
+concentrations	O
+,	O
+desflurane	O
+and	O
+isoflurane	O
+produced	O
+similar	O
+hemodynamic	O
+effects	O
+;	O
+however	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+drugs	O
+that	O
+inhibit	O
+autonomic	O
+reflexes	O
+,	O
+desflurane	O
+had	O
+less	O
+negative	O
+inotropic	O
+activity	O
+and	O
+produced	O
+less	O
+decrease	O
+in	O
+arterial	O
+pressure	O
+.	O
+
+We	O
+report	O
+here	O
+the	O
+isolation	O
+of	O
+a	O
+full	O
+-	O
+length	O
+cDNA	O
+clone	O
+coding	O
+for	O
+a	O
+hitherto	O
+undiscovered	O
+isoform	O
+of	O
+the	O
+bovine	B-GENE
+C	I-GENE
+-	I-GENE
+subunit	I-GENE
+.	O
+
+Isoform	B-GENE
+C	I-GENE
+beta	I-GENE
+2	I-GENE
+,	O
+an	O
+unusual	O
+form	O
+of	O
+the	O
+bovine	O
+catalytic	O
+subunit	O
+of	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+.	O
+
+Salient	O
+applications	O
+of	O
+PB	O
+-	O
+PK	O
+modeling	O
+to	O
+toxicological	O
+problems	O
+are	O
+illustrated	O
+with	O
+examples	O
+.	O
+
+Patients	O
+with	O
+apparently	O
+minor	O
+CT	O
+abnormalities	O
+may	O
+have	O
+significant	O
+epidural	O
+disease	O
+.	O
+
+The	O
+cdr1	B-GENE
+sequence	I-GENE
+includes	O
+an	O
+additional	O
+237	O
+amino	O
+acids	O
+of	O
+the	O
+contiguous	O
+fragment	O
+and	O
+encodes	O
+a	O
+product	O
+of	O
+predicted	O
+Mr	O
+67	O
+,	O
+000	O
+.	O
+
+Armed	O
+with	O
+a	O
+clear	O
+understanding	O
+of	O
+the	O
+pathophysiologic	O
+pathways	O
+that	O
+may	O
+cause	O
+and	O
+/	O
+or	O
+contribute	O
+to	O
+the	O
+development	O
+of	O
+unconjugated	O
+hyperbilirubinemia	O
+and	O
+the	O
+associated	O
+jaundice	O
+,	O
+the	O
+practitioner	O
+will	O
+be	O
+successful	O
+in	O
+helping	O
+the	O
+family	O
+understand	O
+their	O
+child	O
+'	O
+s	O
+illness	O
+.	O
+
+Displacement	O
+thresholds	O
+of	O
+peripheral	O
+sites	O
+in	O
+monocular	O
+human	O
+vision	O
+were	O
+obtained	O
+.	O
+
+The	O
+authors	O
+report	O
+a	O
+case	O
+in	O
+which	O
+stereotactic	O
+irrigation	O
+of	O
+a	O
+brain	O
+cyst	O
+was	O
+temporally	O
+associated	O
+with	O
+respiratory	O
+distress	O
+.	O
+
+ELISA	O
+was	O
+found	O
+to	O
+make	O
+a	O
+contribution	O
+to	O
+the	O
+diagnosis	O
+of	O
+tuberculosis	O
+similar	O
+to	O
+that	O
+of	O
+sputum	O
+smear	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+report	O
+a	O
+detailed	O
+study	O
+of	O
+the	O
+structure	O
+and	O
+the	O
+functional	O
+role	O
+of	O
+the	O
+MalT	B-GENE
+binding	I-GENE
+sites	I-GENE
+located	O
+in	O
+the	O
+adjacent	O
+and	O
+divergent	O
+pulAp	B-GENE
+and	O
+pulCp	B-GENE
+promoters	I-GENE
+.	O
+
+Despite	O
+the	O
+small	O
+number	O
+of	O
+patients	O
+,	O
+on	O
+the	O
+basis	O
+of	O
+this	O
+report	O
+,	O
+we	O
+can	O
+confirm	O
+that	O
+1	O
+.	O
+5	O
+MU	O
+/	O
+day	O
+of	O
+alpha	B-GENE
+-	I-GENE
+IFN	I-GENE
+is	O
+an	O
+adequate	O
+treatment	O
+for	O
+patients	O
+with	O
+hairy	O
+cell	O
+leukemia	O
+.	O
+
+Paroxysmal	O
+fluctuations	O
+in	O
+observed	O
+parasitemia	O
+in	O
+Plasmodium	O
+falciparum	O
+malaria	O
+.	O
+
+No	O
+positive	O
+family	O
+history	O
+was	O
+obtained	O
+.	O
+
+Occupational	O
+asthma	O
+and	O
+rhinoconjunctivitis	O
+from	O
+inhalation	O
+of	O
+crystalline	O
+bovine	B-GENE
+serum	I-GENE
+albumin	I-GENE
+powder	O
+.	O
+
+A	O
+further	O
+subdivision	O
+of	O
+Category	O
+pN1	O
+into	O
+pN1a	O
+(	O
+metastasis	O
+in	O
+single	O
+node	O
+)	O
+and	O
+pN1b	O
+(	O
+two	O
+or	O
+more	O
+nodes	O
+)	O
+is	O
+recommended	O
+.	O
+
+Amino	O
+acid	O
+sequence	O
+comparisons	O
+of	O
+the	O
+E74A	B-GENE
+protein	I-GENE
+reveal	O
+a	O
+highly	O
+conserved	O
+C	O
+-	O
+terminal	O
+region	O
+that	O
+is	O
+rich	O
+in	O
+basic	O
+amino	O
+acid	O
+residues	O
+and	O
+which	O
+has	O
+been	O
+proposed	O
+to	O
+possess	O
+sequence	O
+-	O
+specific	O
+DNA	O
+binding	O
+activity	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+relative	O
+strengths	O
+of	O
+the	O
+promoters	O
+were	O
+similar	O
+in	O
+different	O
+contexts	O
+.	O
+
+Grasso	O
+,	O
+and	O
+A	O
+.	O
+
+After	O
+6	O
+months	O
+,	O
+definite	O
+improvement	O
+in	O
+strength	O
+occurred	O
+in	O
+4	O
+of	O
+7	O
+carnitine	O
+-	O
+treated	O
+patients	O
+and	O
+in	O
+none	O
+of	O
+7	O
+controls	O
+.	O
+
+Age	O
+at	O
+POI	O
+and	O
+asymptote	O
+were	O
+achieved	O
+later	O
+for	O
+Line	O
+RBC2	O
+than	O
+for	O
+Line	O
+F	O
+.	O
+
+To	O
+identify	O
+the	O
+DNA	O
+sequences	O
+that	O
+cis	O
+-	O
+regulate	O
+the	O
+expression	O
+of	O
+the	O
+rat	B-GENE
+liver	I-GENE
+pyruvate	I-GENE
+kinase	I-GENE
+(	O
+L	B-GENE
+-	I-GENE
+PK	I-GENE
+)	O
+genes	O
+,	O
+a	O
+series	O
+of	O
+constructs	O
+in	O
+which	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+reporter	I-GENE
+genes	I-GENE
+is	O
+driven	O
+by	O
+various	O
+deleted	O
+fragments	O
+of	O
+the	O
+3200	O
+base	O
+pairs	O
+(	O
+bp	O
+)	O
+upstream	O
+of	O
+the	O
+L	B-GENE
+-	I-GENE
+PK	I-GENE
+gene	I-GENE
+cap	I-GENE
+site	I-GENE
+have	O
+been	O
+assayed	O
+for	O
+transient	O
+expression	O
+after	O
+introduction	O
+into	O
+hepatoma	O
+HepG2	O
+cells	O
+,	O
+rat	O
+hepatocytes	O
+in	O
+primary	O
+culture	O
+,	O
+fibroblast	O
+LTK	O
+-	O
+cells	O
+,	O
+myogenic	O
+C2C12	O
+cells	O
+,	O
+and	O
+CHO	O
+cells	O
+.	O
+
+The	O
+disturbance	O
+of	O
+pulmonary	O
+gas	O
+exchange	O
+,	O
+as	O
+revealed	O
+by	O
+the	O
+high	O
+value	O
+of	O
+AaDO2	O
+,	O
+existed	O
+without	O
+left	O
+ventricular	O
+dysfunction	O
+,	O
+and	O
+AaDO2	O
+had	O
+no	O
+significant	O
+relationship	O
+with	O
+any	O
+of	O
+the	O
+hemodynamic	O
+parameters	O
+including	O
+the	O
+difference	O
+between	O
+plasma	O
+colloid	O
+osmotic	O
+pressure	O
+and	O
+PCW	O
+.	O
+
+A	O
+dose	O
+of	O
+3	O
+and	O
+6	O
+micrograms	O
+/	O
+kg	O
+/	O
+day	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+reduces	O
+the	O
+severity	O
+of	O
+neutropenia	O
+and	O
+thrombocytopenia	O
+after	O
+carboplatin	O
+-	O
+cyclophosphamide	O
+chemotherapy	O
+,	O
+which	O
+may	O
+lead	O
+to	O
+more	O
+effective	O
+chemotherapy	O
+for	O
+ovarian	O
+cancer	O
+in	O
+the	O
+future	O
+.	O
+
+These	O
+differences	O
+involve	O
+specific	O
+hydrogen	O
+-	O
+bonding	O
+interactions	O
+between	O
+the	O
+protein	O
+and	O
+DNA	O
+,	O
+including	O
+guanine	O
+N7	O
+sites	O
+in	O
+the	O
+major	O
+groove	O
+of	O
+DNA	O
+,	O
+and	O
+alterations	O
+in	O
+DNA	O
+phosphodiester	O
+conformation	O
+induced	O
+by	O
+protein	O
+binding	O
+.	O
+
+Biochemical	O
+analysis	O
+demonstrates	O
+that	O
+the	O
+BJ1	B-GENE
+protein	I-GENE
+is	O
+associated	O
+with	O
+nucleosomes	O
+and	O
+is	O
+released	O
+from	O
+chromatin	O
+by	O
+agents	O
+which	O
+intercalate	O
+into	O
+DNA	O
+,	O
+as	O
+previously	O
+shown	O
+for	O
+the	O
+high	B-GENE
+mobility	I-GENE
+group	I-GENE
+proteins	I-GENE
+(	O
+HMGs	B-GENE
+)	O
+.	O
+
+I	O
+propose	O
+that	O
+their	O
+gene	O
+products	O
+bind	O
+to	O
+the	O
+chromatin	O
+to	O
+establish	O
+or	O
+maintain	O
+a	O
+proper	O
+higher	O
+order	O
+structure	O
+as	O
+a	O
+prerequisite	O
+for	O
+a	O
+regulated	O
+gene	O
+expression	O
+.	O
+
+The	O
+C4BP	B-GENE
+alpha	I-GENE
+gene	I-GENE
+is	O
+organized	O
+as	O
+follows	O
+:	O
+the	O
+first	O
+exon	O
+codes	O
+for	O
+the	O
+first	O
+198	O
+nucleotides	O
+of	O
+the	O
+5	O
+'	O
+UTR	O
+.	O
+
+The	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+Rev	I-GENE
+protein	I-GENE
+is	O
+a	O
+positive	O
+posttranscriptional	O
+regulator	O
+of	O
+viral	O
+structural	O
+gene	O
+expression	O
+and	O
+essential	O
+for	O
+virus	O
+replication	O
+.	O
+
+The	O
+CDC7	B-GENE
+gene	I-GENE
+has	O
+two	O
+in	O
+-	O
+frame	O
+AUG	O
+codons	O
+as	O
+possible	O
+translation	O
+start	O
+sites	O
+,	O
+which	O
+would	O
+produce	O
+58	O
+-	O
+and	O
+56	O
+-	O
+kDa	O
+proteins	O
+,	O
+respectively	O
+.	O
+
+Differences	O
+in	O
+the	O
+clinical	O
+presentation	O
+and	O
+the	O
+gross	O
+appearance	O
+of	O
+the	O
+two	O
+cases	O
+are	O
+described	O
+,	O
+and	O
+similarities	O
+in	O
+the	O
+microscopic	O
+features	O
+are	O
+discussed	O
+.	O
+
+MEASUREMENTS	O
+AND	O
+MAIN	O
+RESULTS	O
+:	O
+The	O
+two	O
+groups	O
+were	O
+similar	O
+on	O
+entry	O
+into	O
+the	O
+study	O
+,	O
+including	O
+mean	O
+FEV1	O
+measurements	O
+(	O
+0	O
+.	O
+70	O
+L	O
+atropine	O
+/	O
+0	O
+.	O
+60	O
+L	O
+metaproterenol	O
+,	O
+P	O
+greater	O
+than	O
+.	O
+05	O
+)	O
+.	O
+
+Using	O
+an	O
+ELISA	O
+,	O
+we	O
+found	O
+that	O
+surfactant	B-GENE
+protein	I-GENE
+A	I-GENE
+(	O
+SP	B-GENE
+-	I-GENE
+A	I-GENE
+)	O
+was	O
+markedly	O
+elevated	O
+in	O
+the	O
+pneumonia	O
+patients	O
+.	O
+
+In	O
+view	O
+of	O
+the	O
+short	O
+t1	O
+/	O
+2	O
+,	O
+we	O
+used	O
+three	O
+doses	O
+/	O
+day	O
+.	O
+
+Temporal	O
+control	O
+of	O
+GUS	B-GENE
+expression	O
+was	O
+found	O
+to	O
+involve	O
+two	O
+negative	O
+regulatory	O
+sequences	O
+,	O
+NRS1	O
+(	O
+-	O
+391	O
+to	O
+-	O
+295	O
+)	O
+and	O
+NRS2	O
+(	O
+-	O
+518	O
+to	O
+-	O
+418	O
+)	O
+,	O
+as	O
+well	O
+as	O
+the	O
+positive	O
+domain	O
+UAS1	O
+.	O
+
+We	O
+purified	O
+a	O
+Ca2	B-GENE
++	I-GENE
+/	I-GENE
+calmodulin	I-GENE
+(	I-GENE
+CaM	I-GENE
+)	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+CaM	B-GENE
+kinase	I-GENE
+)	O
+from	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+with	O
+properties	O
+similar	O
+to	O
+mammalian	B-GENE
+type	I-GENE
+II	I-GENE
+CaM	I-GENE
+kinases	I-GENE
+.	O
+
+In	O
+most	O
+cases	O
+,	O
+DR4	B-GENE
+-	O
+homozygous	O
+,	O
+DRB1	B-GENE
+-	O
+heterozygous	O
+individuals	O
+could	O
+be	O
+genotyped	O
+with	O
+the	O
+panel	O
+of	O
+probes	O
+.	O
+
+The	O
+prevalence	O
+of	O
+opportunistic	O
+infection	O
+among	O
+surviving	O
+AIDS	O
+patients	O
+and	O
+the	O
+probability	O
+of	O
+being	O
+in	O
+tumour	O
+response	O
+following	O
+cancer	O
+therapy	O
+conditional	O
+on	O
+being	O
+alive	O
+are	O
+two	O
+examples	O
+of	O
+such	O
+functions	O
+.	O
+
+Genomic	O
+clones	O
+encompassing	O
+the	O
+human	B-GENE
+ETS1	I-GENE
+gene	I-GENE
+were	O
+isolated	O
+and	O
+utilized	O
+to	O
+define	O
+its	O
+molecular	O
+organization	O
+.	O
+
+Polymerase	O
+chain	O
+reaction	O
+analysis	O
+of	O
+ETS1	B-GENE
+cDNA	I-GENE
+identified	O
+several	O
+amplified	O
+products	O
+,	O
+indicating	O
+alternative	O
+splicing	O
+.	O
+
+Most	O
+of	O
+the	O
+expressed	O
+human	B-GENE
+E3	I-GENE
+polypeptides	I-GENE
+(	O
+five	O
+bands	O
+)	O
+were	O
+found	O
+in	O
+the	O
+insoluble	O
+pellet	O
+while	O
+primarily	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+mature	I-GENE
+E3	I-GENE
+was	O
+found	O
+in	O
+the	O
+soluble	O
+fraction	O
+.	O
+
+To	O
+test	O
+promotor	O
+function	O
+,	O
+chimeric	O
+genes	O
+were	O
+constructed	O
+linking	O
+fragments	O
+of	O
+chicken	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+5	O
+'	O
+-	O
+flanking	O
+DNA	O
+to	O
+a	O
+promoterless	O
+reporter	O
+plasmid	O
+.	O
+
+The	O
+alpha	B-GENE
+4	I-GENE
+gene	I-GENE
+5	O
+'	O
+flanking	O
+region	O
+acted	O
+as	O
+a	O
+promoter	O
+in	O
+transfection	O
+assays	O
+.	O
+
+Characterization	O
+of	O
+the	O
+alpha	B-GENE
+4	I-GENE
+integrin	I-GENE
+gene	I-GENE
+promoter	I-GENE
+.	O
+
+Only	O
+the	O
+3	O
+.	O
+0	O
+-	O
+kb	O
+transcript	O
+was	O
+detected	O
+in	O
+adult	O
+tissues	O
+,	O
+where	O
+its	O
+expression	O
+was	O
+restricted	O
+almost	O
+exclusively	O
+to	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Two	O
+homologues	O
+of	O
+the	O
+rhombotin	B-GENE
+gene	I-GENE
+have	O
+now	O
+been	O
+isolated	O
+.	O
+
+Angina	O
+haemorrhagica	O
+bullosa	O
+causing	O
+respiratory	O
+obstruction	O
+postoperatively	O
+.	O
+
+We	O
+examined	O
+the	O
+effects	O
+of	O
+long	O
+-	O
+term	O
+perfusion	O
+with	O
+pyridoxalated	O
+hemoglobin	B-GENE
+polyoxyethylene	O
+conjugate	O
+(	O
+PHP	O
+)	O
+solution	O
+on	O
+cardiac	O
+function	O
+of	O
+isolated	O
+rat	O
+hearts	O
+.	O
+
+The	O
+gcd2	B-GENE
+-	I-GENE
+503	I-GENE
+mutation	O
+also	O
+results	O
+in	O
+polysome	O
+runoff	O
+,	O
+accumulation	O
+of	O
+inactive	O
+80S	B-GENE
+ribosomal	I-GENE
+couples	I-GENE
+,	O
+and	O
+accumulation	O
+of	O
+at	O
+least	O
+one	O
+of	O
+the	O
+subunits	O
+of	O
+the	O
+general	B-GENE
+translation	I-GENE
+initiation	I-GENE
+factor	I-GENE
+2	I-GENE
+(	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+)	O
+in	O
+43S	B-GENE
+-	O
+48S	B-GENE
+particles	O
+following	O
+a	O
+shift	O
+to	O
+the	O
+restrictive	O
+temperature	O
+.	O
+
+Eight	O
+patients	O
+with	O
+ARC	O
+and	O
+renal	O
+failure	O
+were	O
+recently	O
+evaluated	O
+.	O
+
+To	O
+measure	O
+the	O
+enhancer	O
+activity	O
+of	O
+DR60	B-GENE
+,	O
+a	O
+reporter	O
+plasmid	O
+was	O
+constructed	O
+that	O
+contained	O
+DR60	B-GENE
+cloned	O
+upstream	O
+of	O
+the	O
+reporter	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+gene	I-GENE
+under	O
+the	O
+control	O
+of	O
+the	O
+delayed	O
+-	O
+early	O
+39K	O
+promoter	O
+.	O
+
+A	O
+single	O
+case	O
+of	O
+an	O
+adenocarcinoma	O
+,	O
+arising	O
+in	O
+a	O
+retroperitoneal	O
+enterogenous	O
+cyst	O
+and	O
+which	O
+presented	O
+as	O
+a	O
+left	O
+renal	O
+cyst	O
+,	O
+is	O
+reported	O
+.	O
+
+Using	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+,	O
+we	O
+analyzed	O
+the	O
+U6	B-GENE
+RNA	I-GENE
+genes	I-GENE
+of	O
+52	O
+organisms	O
+.	O
+
+Both	O
+tear	O
+volume	O
+and	O
+tear	O
+flow	O
+were	O
+found	O
+to	O
+be	O
+significantly	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+decreased	O
+up	O
+to	O
+6	O
+h	O
+after	O
+instillation	O
+,	O
+reaching	O
+a	O
+minimum	O
+90	O
+min	O
+after	O
+application	O
+(	O
+tear	O
+volume	O
+:	O
+-	O
+63	O
+%	O
+;	O
+tear	O
+flow	O
+:	O
+-	O
+71	O
+%	O
+)	O
+.	O
+
+Hydrophobicity	O
+analysis	O
+indicated	O
+that	O
+the	O
+KlaA	B-GENE
+and	O
+KlaB	B-GENE
+polypeptides	I-GENE
+are	O
+likely	O
+to	O
+be	O
+soluble	O
+,	O
+whereas	O
+the	O
+KlaC	B-GENE
+polypeptide	I-GENE
+was	O
+predicted	O
+to	O
+have	O
+four	O
+potential	O
+membrane	O
+-	O
+spanning	O
+domains	O
+.	O
+
+To	O
+facilitate	O
+the	O
+availability	O
+of	O
+important	O
+new	O
+therapeutic	O
+agents	O
+,	O
+the	O
+Food	O
+and	O
+Drug	O
+Administration	O
+(	O
+FDA	O
+)	O
+in	O
+the	O
+mid	O
+-	O
+1970s	O
+began	O
+assigning	O
+therapeutic	O
+ratings	O
+to	O
+investigational	O
+new	O
+drugs	O
+and	O
+holding	O
+end	O
+-	O
+of	O
+-	O
+phase	O
+II	O
+conferences	O
+with	O
+drug	O
+sponsors	O
+.	O
+
+In	O
+contrast	O
+,	O
+similar	O
+rates	O
+of	O
+B	O
+.	O
+sphaericus	O
+products	O
+,	O
+ABG	O
+-	O
+6184	O
+technical	O
+powder	O
+and	O
+BSP	O
+-	O
+2	O
+flowable	O
+concentrate	O
+,	O
+produced	O
+no	O
+significant	O
+reduction	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+DNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+complex	I-GENE
+was	O
+difficult	O
+to	O
+obtain	O
+from	O
+dpb2	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	O
+cells	O
+,	O
+suggesting	O
+that	O
+a	O
+stable	O
+DNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+complex	I-GENE
+requires	O
+DPB2	B-GENE
+and	O
+is	O
+essential	O
+for	O
+chromosomal	O
+replication	O
+.	O
+
+To	O
+determine	O
+whether	O
+mononuclear	O
+cell	O
+secretory	O
+products	O
+contribute	O
+to	O
+the	O
+changes	O
+in	O
+bone	O
+turnover	O
+that	O
+characterize	O
+the	O
+development	O
+of	O
+postmenopausal	O
+osteoporosis	O
+,	O
+we	O
+evaluated	O
+the	O
+effects	O
+of	O
+oophorectomy	O
+and	O
+subsequent	O
+estrogen	O
+replacement	O
+on	O
+the	O
+spontaneous	O
+secretion	O
+of	O
+interleukin	B-GENE
+1	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+and	O
+on	O
+the	O
+phytohemagglutinin	B-GENE
+A	I-GENE
+-	O
+induced	O
+secretion	O
+of	O
+granulocyte	B-GENE
+-	I-GENE
+macrophage	I-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+from	O
+peripheral	O
+blood	O
+mononuclear	O
+cells	O
+.	O
+
+There	O
+were	O
+45	O
+to	O
+56	O
+nt	O
+differences	O
+between	O
+the	O
+virulent	O
+and	O
+avirulent	O
+groups	O
+while	O
+there	O
+were	O
+6	O
+to	O
+14	O
+nt	O
+differences	O
+among	O
+four	O
+avirulent	O
+strains	O
+.	O
+
+The	O
+standard	O
+principles	O
+of	O
+surgical	O
+management	O
+must	O
+be	O
+adhered	O
+to	O
+when	O
+using	O
+Sandostatin	O
+to	O
+treat	O
+patients	O
+with	O
+these	O
+disorders	O
+.	O
+
+Some	O
+of	O
+the	O
+PCR	O
+products	O
+contained	O
+mutations	O
+in	O
+ATG1	B-GENE
+and	O
+/	O
+or	O
+ATG2	B-GENE
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+the	O
+levels	O
+of	O
+oxygen	O
+free	O
+radicals	O
+were	O
+increased	O
+in	O
+hepatocytes	O
+and	O
+mitochondria	O
+.	O
+
+The	O
+sequence	O
+of	O
+the	O
+pMxL1	O
+plasmid	O
+containing	O
+the	O
+invertible	O
+region	O
+contains	O
+a	O
+perfect	O
+tandem	O
+repeat	O
+of	O
+19	O
+bp	O
+in	O
+the	O
+orientation	O
+1	O
+nonexpressed	O
+pilin	B-GENE
+gene	I-GENE
+at	O
+the	O
+middle	O
+of	O
+the	O
+recombination	O
+junction	O
+site	O
+.	O
+
+No	O
+evidence	O
+for	O
+the	O
+presence	O
+of	O
+introns	O
+within	O
+the	O
+acvA	B-GENE
+gene	I-GENE
+has	O
+been	O
+found	O
+.	O
+
+These	O
+observations	O
+,	O
+together	O
+with	O
+the	O
+occurrence	O
+of	O
+putative	O
+4	O
+'	O
+-	O
+phosphopantetheine	O
+-	O
+attachment	O
+sites	O
+and	O
+a	O
+putative	O
+thioesterase	B-GENE
+site	I-GENE
+,	O
+are	O
+discussed	O
+with	O
+reference	O
+to	O
+the	O
+reaction	O
+sequence	O
+leading	O
+to	O
+production	O
+of	O
+the	O
+ACV	B-GENE
+tripeptide	I-GENE
+.	O
+
+Pargyline	O
+,	O
+a	O
+monoamine	B-GENE
+oxidase	I-GENE
+inhibitor	O
+,	O
+reduces	O
+peak	O
+3	O
+transiently	O
+(	O
+max	O
+.	O
+
+When	O
+given	O
+the	O
+choice	O
+between	O
+an	O
+estrous	O
+female	O
+and	O
+a	O
+sexually	O
+active	O
+male	O
+in	O
+the	O
+AOF	O
+,	O
+flutamide	O
+females	O
+,	O
+as	O
+well	O
+as	O
+controls	O
+,	O
+preferred	O
+the	O
+male	O
+partner	O
+.	O
+
+Hypoxic	O
+ventilatory	O
+responses	O
+were	O
+-	O
+1	O
+.	O
+99	O
++	O
+/	O
+-	O
+0	O
+.	O
+37	O
+L	O
+/	O
+min	O
+/	O
+%	O
+SaO2	O
+in	O
+the	O
+relatives	O
+and	O
+-	O
+1	O
+.	O
+54	O
++	O
+/	O
+-	O
+0	O
+.	O
+25	O
+L	O
+/	O
+min	O
+/	O
+%	O
+SaO2	O
+in	O
+the	O
+control	O
+subjects	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Very	O
+small	O
+deletions	O
+within	O
+the	O
+conserved	O
+region	O
+completely	O
+abolished	O
+transforming	O
+activity	O
+of	O
+dbl	B-GENE
+,	O
+while	O
+extensive	O
+deletion	O
+outside	O
+of	O
+this	O
+region	O
+had	O
+no	O
+effect	O
+.	O
+
+This	O
+computerized	O
+list	O
+was	O
+linked	O
+to	O
+the	O
+central	O
+files	O
+of	O
+the	O
+Massachusetts	O
+Cancer	O
+Registry	O
+and	O
+cases	O
+diagnosed	O
+between	O
+1982	O
+and	O
+1988	O
+were	O
+identified	O
+.	O
+
+We	O
+also	O
+present	O
+evidence	O
+for	O
+a	O
+negative	O
+regulatory	O
+element	O
+in	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+Mlu	B-GENE
+I	I-GENE
+upstream	I-GENE
+activation	I-GENE
+sequence	I-GENE
+.	O
+
+Mechanism	O
+of	O
+activation	O
+of	O
+the	O
+vav	B-GENE
+protooncogene	I-GENE
+.	O
+vav	B-GENE
+is	O
+a	O
+human	O
+locus	O
+that	O
+appears	O
+to	O
+be	O
+specifically	O
+expressed	O
+in	O
+cells	O
+of	O
+hematopoietic	O
+origin	O
+regardless	O
+of	O
+their	O
+differentiation	O
+lineage	O
+.	O
+
+Endothelial	O
+cell	O
+seeding	O
+.	O
+
+Menetrier	O
+disease	O
+in	O
+a	O
+child	O
+.	O
+
+After	O
+hemodynamic	O
+stabilization	O
+,	O
+the	O
+goal	O
+of	O
+therapy	O
+is	O
+to	O
+diminish	O
+the	O
+chance	O
+that	O
+an	O
+ulcer	O
+will	O
+continue	O
+to	O
+bleed	O
+or	O
+will	O
+rebleed	O
+.	O
+
+Thirty	O
+seven	O
+patients	O
+(	O
+amitriptyline	O
+n	O
+=	O
+16	O
+,	O
+moclobemide	O
+n	O
+=	O
+21	O
+)	O
+completed	O
+the	O
+six	O
+week	O
+protocol	O
+,	O
+which	O
+was	O
+conducted	O
+under	O
+double	O
+blind	O
+conditions	O
+.	O
+
+The	O
+stimulus	O
+threshold	O
+for	O
+EER	O
+showed	O
+a	O
+less	O
+individual	O
+variation	O
+than	O
+amplitude	O
+.	O
+
+Analysis	O
+of	O
+electrically	O
+evoked	O
+response	O
+(	O
+EER	O
+)	O
+in	O
+relation	O
+to	O
+the	O
+central	O
+visual	O
+pathway	O
+of	O
+the	O
+cat	O
+(	O
+1	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+plasma	O
+fibrinogen	B-GENE
+levels	O
+increased	O
+by	O
+a	O
+mean	O
+of	O
+17	O
+.	O
+6	O
+%	O
+,	O
+a	O
+potentially	O
+adverse	O
+effect	O
+of	O
+gemfibrozil	O
+that	O
+has	O
+not	O
+been	O
+previously	O
+reported	O
+.	O
+
+Gemfibrozil	O
+in	O
+hyperlipidaemic	O
+patients	O
+with	O
+peripheral	O
+arterial	O
+disease	O
+:	O
+some	O
+undiscovered	O
+actions	O
+.	O
+
+An	O
+RME1	B-GENE
+-	O
+independent	O
+pathway	O
+for	O
+sporulation	O
+control	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+acts	O
+through	O
+IME1	B-GENE
+transcript	I-GENE
+accumulation	O
+.	O
+
+The	O
+role	O
+of	O
+pharmacological	O
+profiling	O
+in	O
+safety	O
+assessment	O
+.	O
+
+Its	O
+application	O
+in	O
+Madagascar	O
+:	O
+advantages	O
+and	O
+disadvantages	O
+
+The	O
+authors	O
+evaluate	O
+the	O
+clinical	O
+efficacy	O
+of	O
+EMB	O
+AZS	O
+in	O
+recurrent	O
+ulcer	O
+after	O
+operation	O
+on	O
+the	O
+stomach	O
+caused	O
+by	O
+a	O
+high	O
+level	O
+of	O
+acid	O
+production	O
+and	O
+ulcerative	O
+gastroduodenal	O
+bleeding	O
+.	O
+
+To	O
+investigate	O
+the	O
+regulation	O
+of	O
+Spec	B-GENE
+gene	I-GENE
+activity	O
+,	O
+the	O
+region	O
+around	O
+the	O
+Spec1	B-GENE
+transcriptional	I-GENE
+initiation	I-GENE
+site	I-GENE
+was	O
+analyzed	O
+for	O
+sites	O
+of	O
+protein	O
+-	O
+DNA	O
+interaction	O
+.	O
+
+Phosphopeptide	O
+mapping	O
+revealed	O
+the	O
+same	O
+autophosphorylation	O
+sites	O
+utilized	O
+by	O
+EGFR	B-GENE
+-	I-GENE
+IC	I-GENE
+as	O
+those	O
+identified	O
+in	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+EGFR	I-GENE
+.	O
+
+The	O
+encoded	O
+sequence	O
+revealed	O
+a	O
+typical	O
+signal	O
+peptide	O
+,	O
+a	O
+predominantly	O
+hydrophilic	O
+707	O
+amino	O
+acid	O
+residue	O
+domain	O
+with	O
+8	O
+N	O
+-	O
+glycosylation	O
+sites	O
+,	O
+a	O
+transmembrane	O
+domain	O
+,	O
+and	O
+a	O
+C	O
+-	O
+terminal	O
+domain	O
+of	O
+52	O
+amino	O
+acids	O
+.	O
+
+The	O
+TCF	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+binding	I-GENE
+site	I-GENE
+was	O
+also	O
+required	O
+for	O
+TCR	B-GENE
+alpha	I-GENE
+enhancer	I-GENE
+activity	O
+in	O
+transcriptionally	O
+active	O
+extracts	O
+from	O
+Jurkat	O
+but	O
+not	O
+HeLa	O
+cells	O
+,	O
+confirming	O
+that	O
+TCF	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+is	O
+a	O
+T	B-GENE
+-	I-GENE
+cell	I-GENE
+-	I-GENE
+specific	I-GENE
+transcription	I-GENE
+factor	I-GENE
+.	O
+
+A	O
+new	O
+semi	O
+-	O
+automatic	O
+method	O
+for	O
+quantifying	O
+regional	O
+cerebral	O
+uptake	O
+of	O
+99m	O
+technetium	O
+-	O
+hexamethylpropylene	O
+amine	O
+oxime	O
+(	O
+99mTc	O
+-	O
+HMPAO	O
+)	O
+was	O
+used	O
+to	O
+assess	O
+single	O
+photon	O
+emission	O
+tomograms	O
+from	O
+5	O
+normal	O
+subjects	O
+,	O
+14	O
+patients	O
+with	O
+Alzheimer	O
+'	O
+s	O
+disease	O
+,	O
+14	O
+patients	O
+with	O
+dementia	O
+of	O
+frontal	O
+lobe	O
+type	O
+and	O
+4	O
+patients	O
+with	O
+dementia	O
+with	O
+motor	O
+neurone	O
+disease	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+fog	O
+,	O
+up	O
+to	O
+a	O
+level	O
+of	O
+base	O
+plus	O
+fog	O
+of	O
+0	O
+.	O
+6	O
+optical	O
+density	O
+units	O
+,	O
+had	O
+no	O
+influence	O
+on	O
+the	O
+diagnostic	O
+accuracy	O
+in	O
+the	O
+absence	O
+of	O
+any	O
+compensation	O
+.	O
+
+IdB	O
+1031	O
+was	O
+first	O
+extracted	O
+by	O
+liquid	O
+-	O
+solid	O
+partition	O
+and	O
+the	O
+extracts	O
+were	O
+evaporated	O
+and	O
+analysed	O
+on	O
+a	O
+reversed	O
+-	O
+phase	O
+column	O
+under	O
+isocratic	O
+conditions	O
+,	O
+using	O
+either	O
+an	O
+electrochemical	O
+or	O
+a	O
+UV	O
+detector	O
+.	O
+
+In	O
+this	O
+model	O
+,	O
+eltoprazine	O
+has	O
+a	O
+very	O
+specific	O
+anti	O
+-	O
+aggressive	O
+(	O
+serenic	O
+)	O
+profile	O
+,	O
+inhibiting	O
+aggression	O
+while	O
+social	O
+interaction	O
+and	O
+exploration	O
+are	O
+not	O
+decreased	O
+but	O
+even	O
+enhanced	O
+;	O
+inactivity	O
+,	O
+a	O
+measure	O
+for	O
+sedation	O
+,	O
+is	O
+not	O
+affected	O
+.	O
+
+A	O
+new	O
+method	O
+for	O
+the	O
+in	O
+vitro	O
+transfer	O
+of	O
+delayed	O
+hypersensitivity	O
+by	O
+dialysed	O
+transfer	B-GENE
+factor	I-GENE
+.	O
+
+Effect	O
+of	O
+separate	O
+and	O
+combined	O
+effects	O
+of	O
+plutonium	O
+-	O
+239	O
+,	O
+hexachlorobutadiene	O
+and	O
+tributyl	O
+phosphate	O
+on	O
+the	O
+thymus	O
+gland	O
+of	O
+rats	O
+
+Data	O
+collection	O
+was	O
+made	O
+with	O
+a	O
+query	O
+language	O
+,	O
+and	O
+data	O
+analysis	O
+performed	O
+with	O
+an	O
+interactive	O
+knowledge	O
+-	O
+based	O
+statistical	O
+tool	O
+,	O
+MAXITAB	O
+,	O
+employing	O
+a	O
+multivariate	O
+tabular	O
+analysis	O
+technique	O
+.	O
+
+ARPIA	O
+has	O
+been	O
+implemented	O
+by	O
+using	O
+a	O
+relational	O
+DBMS	O
+,	O
+very	O
+cheap	O
+and	O
+highly	O
+diffused	O
+on	O
+personal	O
+computers	O
+.	O
+
+Diuresis	O
+was	O
+induced	O
+by	O
+scheduled	O
+drinking	O
+of	O
+tea	O
+(	O
+150	O
+ml	O
+/	O
+h	O
+)	O
+.	O
+
+Diagnostic	O
+value	O
+of	O
+adenosine	B-GENE
+deaminase	I-GENE
+activity	O
+in	O
+tuberculous	O
+effusions	O
+.	O
+
+Femoral	O
+strain	O
+adaptation	O
+after	O
+total	O
+hip	O
+replacement	O
+:	O
+a	O
+comparison	O
+of	O
+cemented	O
+and	O
+porous	O
+ingrowth	O
+components	O
+in	O
+canines	O
+.	O
+
+Immuno	O
+-	O
+cytochemistry	O
+,	O
+using	O
+antisera	O
+against	O
+Campylobacter	O
+jejuni	O
+,	O
+showed	O
+that	O
+the	O
+positive	O
+staining	O
+in	O
+altered	O
+epithelial	O
+cells	O
+were	O
+restricted	O
+to	O
+intracellular	O
+organisms	O
+having	O
+a	O
+structure	O
+resembling	O
+Campylobacter	O
+spp	O
+.	O
+
+Promoter	O
+activities	O
+were	O
+estimated	O
+using	O
+beta	B-GENE
+-	I-GENE
+glucuronidase	I-GENE
+and	O
+neomycin	B-GENE
+phosphotransferase	I-GENE
+II	I-GENE
+reporter	I-GENE
+gene	I-GENE
+systems	I-GENE
+.	O
+
+The	O
+5	O
+'	O
+regions	O
+of	O
+these	O
+two	O
+soybean	B-GENE
+actin	I-GENE
+genes	I-GENE
+contain	O
+many	O
+unusual	O
+features	O
+including	O
+(	O
+CT	O
+)	O
+repeats	O
+and	O
+long	O
+stretches	O
+of	O
+pyrimidine	O
+-	O
+rich	O
+DNA	O
+.	O
+
+All	O
+8	O
+(	O
+100	O
+%	O
+)	O
+patients	O
+with	O
+fulminant	O
+hepatic	O
+failure	O
+who	O
+received	O
+grafts	O
+survived	O
+,	O
+including	O
+3	O
+who	O
+received	O
+ABO	O
+-	O
+incompatible	O
+grafts	O
+,	O
+though	O
+2	O
+of	O
+these	O
+subsequently	O
+required	O
+retransplantation	O
+.	O
+
+No	O
+patient	O
+had	O
+a	O
+history	O
+of	O
+excess	O
+alcohol	O
+intake	O
+,	O
+or	O
+prolonged	O
+intake	O
+of	O
+hepatotoxic	O
+drugs	O
+and	O
+steroids	O
+,	O
+and	O
+were	O
+not	O
+obese	O
+or	O
+malnourished	O
+.	O
+
+An	O
+evolutionary	O
+comparison	O
+of	O
+amino	O
+acid	O
+sequences	O
+of	O
+34	O
+HSP70	B-GENE
+proteins	I-GENE
+from	O
+17	O
+species	O
+suggests	O
+that	O
+BiP	B-GENE
+genes	I-GENE
+share	O
+a	O
+common	O
+ancestor	O
+,	O
+which	O
+diverged	O
+from	O
+other	O
+HSP70	B-GENE
+genes	I-GENE
+near	O
+the	O
+time	O
+when	O
+eukaryotes	O
+first	O
+appeared	O
+.	O
+
+Spore	O
+inocula	O
+(	O
+approximately	O
+10	O
+(	O
+6	O
+)	O
+/	O
+coupon	O
+)	O
+were	O
+dried	O
+onto	O
+0	O
+.	O
+5	O
+-	O
+in	O
+.	O
+
+However	O
+,	O
+overexpression	O
+of	O
+both	O
+the	O
+STE4	B-GENE
+and	O
+STE18	B-GENE
+proteins	I-GENE
+did	O
+not	O
+generate	O
+a	O
+stronger	O
+pheromone	O
+response	O
+than	O
+overexpression	O
+of	O
+STE4	B-GENE
+in	O
+the	O
+presence	O
+of	O
+wild	O
+-	O
+type	O
+levels	O
+of	O
+STE18	B-GENE
+.	O
+
+Reverse	O
+transcription	O
+-	O
+PCR	O
+was	O
+then	O
+used	O
+to	O
+clone	O
+from	O
+human	O
+poly	O
+(	O
+A	O
+)	O
++	O
+RNA	O
+the	O
+cDNA	O
+corresponding	O
+to	O
+the	O
+expressed	O
+homolog	O
+of	O
+psi	B-GENE
+ARF	I-GENE
+4	I-GENE
+,	O
+referred	O
+to	O
+as	O
+human	B-GENE
+ARF	I-GENE
+4	I-GENE
+.	O
+
+To	O
+evaluate	O
+the	O
+cost	O
+and	O
+benefits	O
+of	O
+screening	O
+tests	O
+for	O
+Chlamydia	O
+trachomatis	O
+in	O
+adolescent	O
+males	O
+,	O
+we	O
+developed	O
+a	O
+decision	O
+analysis	O
+model	O
+and	O
+compared	O
+the	O
+leukocyte	B-GENE
+esterase	I-GENE
+urine	O
+dipstick	O
+test	O
+with	O
+culture	O
+,	O
+with	O
+direct	O
+-	O
+smear	O
+fluorescent	O
+antibody	O
+(	O
+DFA	O
+)	O
+,	O
+and	O
+with	O
+the	O
+option	O
+of	O
+no	O
+screening	O
+(	O
+no	O
+treatment	O
+)	O
+.	O
+
+Sequencing	O
+the	O
+gene	O
+for	O
+an	O
+imipenem	O
+-	O
+cefoxitin	O
+-	O
+hydrolyzing	O
+enzyme	O
+(	O
+CfiA	B-GENE
+)	O
+from	O
+Bacteroides	O
+fragilis	O
+TAL2480	O
+reveals	O
+strong	O
+similarity	O
+between	O
+CfiA	B-GENE
+and	O
+Bacillus	B-GENE
+cereus	I-GENE
+beta	I-GENE
+-	I-GENE
+lactamase	I-GENE
+II	I-GENE
+.	O
+
+The	O
+cloned	O
+HindIII	B-GENE
+fragment	I-GENE
+,	O
+which	O
+was	O
+shown	O
+by	O
+DNA	O
+sequence	O
+analysis	O
+to	O
+encode	O
+the	O
+N	O
+-	O
+terminal	O
+half	O
+of	O
+the	O
+B	B-GENE
+.	I-GENE
+subtilis	I-GENE
+IF2	I-GENE
+protein	I-GENE
+and	O
+0	O
+.	O
+2	O
+kb	O
+of	O
+upstream	O
+flanking	O
+sequence	O
+,	O
+was	O
+utilized	O
+as	O
+a	O
+homologous	O
+probe	O
+to	O
+clone	O
+an	O
+overlapping	O
+2	B-GENE
+.	I-GENE
+76	I-GENE
+-	I-GENE
+kb	I-GENE
+ClaI	I-GENE
+chromosomal	I-GENE
+fragment	I-GENE
+containing	O
+the	O
+entire	B-GENE
+IF2	I-GENE
+structural	I-GENE
+gene	I-GENE
+.	O
+
+Maternal	O
+seizures	O
+had	O
+occurred	O
+during	O
+pregnancy	O
+in	O
+52	O
+per	O
+cent	O
+.	O
+
+It	O
+encodes	O
+a	O
+protein	O
+with	O
+three	O
+zinc	O
+fingers	O
+similar	O
+to	O
+those	O
+of	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+Sp1	I-GENE
+.	O
+
+Krox	B-GENE
+-	I-GENE
+24	I-GENE
+is	O
+therefore	O
+a	O
+sequence	O
+-	O
+specific	O
+transcriptional	O
+activator	O
+.	O
+
+The	O
+interindividual	O
+variability	O
+of	O
+the	O
+parameters	O
+is	O
+taken	O
+into	O
+consideration	O
+by	O
+interactively	O
+determining	O
+the	O
+threshold	O
+levels	O
+.	O
+
+Inspired	O
+CO2	O
+causing	O
+changes	O
+from	O
+hypo	O
+-	O
+to	O
+normocapnia	O
+has	O
+previously	O
+been	O
+shown	O
+to	O
+improve	O
+arterial	O
+O2	O
+tension	O
+(	O
+PaO2	O
+)	O
+and	O
+to	O
+reduce	O
+alveolar	O
+-	O
+arterial	O
+O2	O
+difference	O
+.	O
+
+Expression	O
+,	O
+nucleotide	O
+sequence	O
+and	O
+mutational	O
+analysis	O
+of	O
+two	O
+open	O
+reading	O
+frames	O
+in	O
+the	O
+nif	B-GENE
+gene	I-GENE
+region	I-GENE
+of	I-GENE
+Anabaena	I-GENE
+sp	I-GENE
+.	I-GENE
+strain	I-GENE
+PCC7120	I-GENE
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+a	O
+sequence	O
+match	O
+between	O
+enhancers	O
+and	O
+certain	O
+promoter	O
+elements	O
+is	O
+critical	O
+.	O
+
+This	O
+Mr	O
+is	O
+similar	O
+to	O
+those	O
+of	O
+the	O
+purified	B-GENE
+smg	I-GENE
+p25A	I-GENE
+GDI	I-GENE
+estimated	O
+by	O
+sodium	O
+dodecyl	O
+sulfate	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+and	O
+sucrose	O
+density	O
+gradient	O
+ultracentrifugation	O
+,	O
+which	O
+are	O
+about	O
+54	O
+,	O
+000	O
+and	O
+65	O
+,	O
+000	O
+,	O
+respectively	O
+.	O
+
+Yeast	O
+mutants	O
+assigned	O
+to	O
+the	O
+pet	B-GENE
+complementation	O
+group	O
+G104	O
+were	O
+found	O
+to	O
+lack	O
+alpha	B-GENE
+-	I-GENE
+ketoglutarate	I-GENE
+dehydrogenase	I-GENE
+activity	O
+as	O
+a	O
+result	O
+of	O
+mutations	O
+in	O
+the	O
+dihydrolipoyl	B-GENE
+transsuccinylase	I-GENE
+(	O
+KE2	B-GENE
+)	O
+component	O
+of	O
+the	O
+complex	O
+.	O
+
+Critical	O
+residues	O
+required	O
+for	O
+repression	O
+are	O
+located	O
+within	O
+the	O
+C	O
+-	O
+terminal	O
+27	O
+amino	O
+acids	O
+of	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+,	O
+since	O
+v	B-GENE
+-	I-GENE
+Fos	I-GENE
+and	O
+C	O
+-	O
+terminal	O
+truncations	O
+of	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+did	O
+not	O
+down	O
+regulate	O
+.	O
+
+We	O
+also	O
+discovered	O
+a	O
+V	B-GENE
+lambda	I-GENE
+pseudogene	I-GENE
+,	O
+called	O
+psi	B-GENE
+V	I-GENE
+lambda	I-GENE
+1	I-GENE
+,	O
+3	O
+kb	O
+upstream	O
+of	O
+the	O
+U266	B-GENE
+lambda	I-GENE
+gene	I-GENE
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+have	O
+analyzed	O
+the	O
+structure	O
+of	O
+human	O
+gene	O
+for	O
+Gx	B-GENE
+alpha	I-GENE
+,	O
+which	O
+spans	O
+more	O
+than	O
+60	O
+kilobases	O
+.	O
+
+A	O
+long	O
+follow	O
+-	O
+up	O
+study	O
+revealed	O
+that	O
+convalescent	O
+stage	O
+children	O
+still	O
+have	O
+the	O
+potency	O
+to	O
+have	O
+an	O
+immediate	O
+type	O
+hypersensitivity	O
+reaction	O
+on	O
+exposure	O
+to	O
+mite	O
+antigen	O
+,	O
+with	O
+a	O
+high	O
+titer	O
+of	O
+mite	B-GENE
+specific	I-GENE
+IgE	I-GENE
+in	O
+their	O
+sera	O
+,	O
+but	O
+they	O
+are	O
+free	O
+from	O
+asthmatic	O
+attacks	O
+because	O
+of	O
+the	O
+reduction	O
+in	O
+the	O
+amount	O
+of	O
+mite	O
+antigen	O
+in	O
+the	O
+body	O
+,	O
+as	O
+shown	O
+by	O
+the	O
+reduction	O
+in	O
+the	O
+amount	O
+of	O
+mite	B-GENE
+specific	I-GENE
+IgG	I-GENE
+.	O
+
+But	O
+no	O
+influence	O
+was	O
+observed	O
+at	O
+lower	O
+concentrations	O
+than	O
+1	O
+/	O
+4	O
+MIC	O
+of	O
+AMK	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+notice	O
+two	O
+potential	O
+consensus	O
+motifs	O
+which	O
+are	O
+also	O
+found	O
+in	O
+corresponding	O
+positions	O
+in	O
+the	O
+genes	O
+for	O
+the	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+and	O
+the	O
+68	B-GENE
+-	I-GENE
+kDa	I-GENE
+neurofilament	I-GENE
+protein	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+-	O
+119	O
+to	O
+-	O
+81	O
+fragment	O
+of	O
+the	O
+CCK	B-GENE
+promoter	I-GENE
+contains	O
+a	O
+transcriptional	O
+enhancer	O
+that	O
+potentiates	O
+the	O
+transcription	O
+from	O
+the	O
+herpes	O
+simplex	O
+virus	O
+thymidine	B-GENE
+kinase	I-GENE
+promoter	I-GENE
+in	O
+a	O
+position	O
+-	O
+and	O
+orientation	O
+-	O
+independent	O
+manner	O
+.	O
+
+Thirty	O
+minutes	O
+of	O
+supine	O
+restraint	O
+decreased	O
+DOPAC	O
+concentrations	O
+in	O
+the	O
+median	O
+eminence	O
+of	O
+female	O
+rats	O
+that	O
+were	O
+not	O
+exposed	O
+to	O
+ether	O
+,	O
+and	O
+brief	O
+exposure	O
+to	O
+ether	O
+enhanced	O
+this	O
+effect	O
+.	O
+
+Influence	O
+of	O
+metoprolol	O
+treatment	O
+on	O
+sympatho	O
+-	O
+adrenal	O
+activation	O
+of	O
+fibrinolysis	O
+.	O
+
+Five	O
+of	O
+10	O
+scars	O
+studied	O
+decreased	O
+at	O
+least	O
+50	O
+%	O
+in	O
+linear	O
+dimensions	O
+.	O
+
+Managing	O
+dysphagia	O
+in	O
+a	O
+chronic	O
+care	O
+setting	O
+:	O
+an	O
+introduction	O
+.	O
+
+Gel	O
+-	O
+mobility	O
+-	O
+shift	O
+assays	O
+confirmed	O
+that	O
+the	O
+Raji	O
+nuclear	O
+proteins	O
+that	O
+bound	O
+to	O
+W	O
+and	O
+V	O
+elements	O
+were	O
+competed	O
+with	O
+by	O
+an	O
+HLA	B-GENE
+-	I-GENE
+DRA	I-GENE
+X	I-GENE
+-	I-GENE
+box	I-GENE
+oligonucleotide	I-GENE
+.	O
+
+The	O
+NF1	B-GENE
+locus	I-GENE
+encodes	O
+a	O
+protein	O
+functionally	O
+related	O
+to	O
+mammalian	B-GENE
+GAP	I-GENE
+and	O
+yeast	B-GENE
+IRA	I-GENE
+proteins	I-GENE
+.	O
+
+A	O
+second	O
+isotype	O
+of	O
+Raja	B-GENE
+immunoglobulin	I-GENE
+heavy	I-GENE
+chain	I-GENE
+genes	I-GENE
+has	O
+been	O
+detected	O
+by	O
+screening	O
+a	O
+spleen	O
+cDNA	O
+library	O
+with	O
+homologous	O
+Raja	B-GENE
+VH	I-GENE
+-	O
+and	O
+CH1	B-GENE
+-	O
+specific	O
+probes	O
+complementing	O
+the	O
+respective	O
+regions	O
+of	O
+the	O
+mu	B-GENE
+-	I-GENE
+like	I-GENE
+isotype	I-GENE
+.	O
+
+Petko	O
+,	O
+and	O
+S	O
+.	O
+
+Disruption	O
+of	O
+ARF2	B-GENE
+causes	O
+no	O
+detectable	O
+phenotype	O
+.	O
+
+Human	O
+recombinant	O
+DNA	O
+-	O
+derived	O
+antihemophilic	B-GENE
+factor	I-GENE
+(	O
+factor	B-GENE
+VIII	I-GENE
+)	O
+in	O
+the	O
+treatment	O
+of	O
+hemophilia	O
+A	O
+.	O
+recombinant	O
+Factor	B-GENE
+VIII	I-GENE
+Study	O
+Group	O
+.	O
+
+Like	O
+other	O
+members	O
+of	O
+this	O
+family	O
+,	O
+the	O
+AP	B-GENE
+-	I-GENE
+4	I-GENE
+HLH	O
+motif	O
+and	O
+the	O
+adjacent	O
+basic	O
+domain	O
+are	O
+necessary	O
+and	O
+sufficient	O
+to	O
+confer	O
+site	O
+-	O
+specific	O
+DNA	O
+binding	O
+.	O
+
+Furthermore	O
+,	O
+expression	O
+of	O
+the	O
+promoter	O
+in	O
+embryonic	O
+Drosophila	O
+melanogaster	O
+cells	O
+that	O
+lack	O
+MyoD1	B-GENE
+and	O
+Sp1	B-GENE
+is	O
+strictly	O
+dependent	O
+on	O
+all	O
+three	O
+sites	O
+remaining	O
+intact	O
+and	O
+on	O
+the	O
+presence	O
+of	O
+exogenously	O
+supplied	O
+Sp1	B-GENE
+and	O
+MyoD1	B-GENE
+.	O
+
+Effects	O
+of	O
+a	O
+selective	O
+monoamine	B-GENE
+oxidase	I-GENE
+(	I-GENE
+MAO	I-GENE
+)	I-GENE
+-	I-GENE
+-	I-GENE
+A	I-GENE
+inhibitor	O
+,	O
+clorgyline	O
+,	O
+a	O
+selective	O
+MAO	B-GENE
+-	I-GENE
+B	I-GENE
+inhibitor	O
+,	O
+deprenyl	O
+,	O
+and	O
+a	O
+non	O
+-	O
+selective	O
+MAO	B-GENE
+inhibitor	O
+,	O
+nialamide	O
+,	O
+were	O
+investigated	O
+on	O
+footshock	O
+-	O
+induced	O
+aggression	O
+(	O
+FIA	O
+)	O
+in	O
+paired	O
+rats	O
+.	O
+
+To	O
+identify	O
+structural	O
+features	O
+of	O
+residues	O
+flanking	O
+the	O
+c	O
+-	O
+region	O
+that	O
+influence	O
+the	O
+fidelity	O
+and	O
+efficiency	O
+of	O
+signal	O
+peptidase	O
+cleavage	O
+as	O
+well	O
+as	O
+co	O
+-	O
+translational	O
+translocation	O
+,	O
+we	O
+introduced	O
+six	O
+amino	O
+acid	O
+substitutions	O
+into	O
+the	O
+COOH	O
+terminus	O
+of	O
+the	O
+hydrophobic	O
+core	O
+and	O
+seven	O
+substitutions	O
+at	O
+the	O
+NH2	O
+terminus	O
+of	O
+the	O
+mature	O
+region	O
+(	O
+the	O
++	O
+1	O
+position	O
+)	O
+of	O
+a	O
+model	O
+eukaryotic	B-GENE
+preprotein	I-GENE
+-	I-GENE
+human	I-GENE
+pre	I-GENE
+(	I-GENE
+delta	I-GENE
+pro	I-GENE
+)	I-GENE
+apoA	I-GENE
+-	I-GENE
+II	I-GENE
+.	O
+
+Additionally	O
+,	O
+although	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+and	O
+egr	B-GENE
+-	I-GENE
+1	I-GENE
+mRNAs	I-GENE
+are	O
+expressed	O
+at	O
+elevated	O
+levels	O
+in	O
+stimulated	O
+liver	O
+cells	O
+,	O
+fos	B-GENE
+-	I-GENE
+B	I-GENE
+,	O
+fra	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+egr	B-GENE
+-	I-GENE
+2	I-GENE
+are	O
+not	O
+,	O
+which	O
+suggests	O
+that	O
+factors	O
+in	O
+addition	O
+to	O
+the	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+participate	O
+in	O
+the	O
+regulation	O
+of	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+gene	I-GENE
+induction	O
+.	O
+
+Of	O
+848	O
+patients	O
+,	O
+819	O
+cases	O
+with	O
+complete	O
+description	O
+of	O
+patient	O
+'	O
+s	O
+background	O
+were	O
+evaluable	O
+:	O
+Group	O
+A	O
+(	O
+surgery	O
++	O
+MMC	O
++	O
+5	O
+-	O
+FU	O
+:	O
+chemotherapy	O
+)	O
+253	O
+cases	O
+,	O
+group	O
+B	O
+(	O
+surgery	O
++	O
+MMC	O
++	O
+5	O
+-	O
+FU	O
++	O
+OK	O
+-	O
+432	O
+or	O
+PSK	O
+:	O
+immunochemotherapy	O
+)	O
+282	O
+and	O
+group	O
+C	O
+(	O
+surgery	O
+alone	O
+)	O
+284	O
+.	O
+
+The	O
+nuclear	O
+proteins	O
+encoded	O
+by	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+protooncogenes	I-GENE
+are	O
+expressed	O
+during	O
+the	O
+proliferation	O
+period	O
+of	O
+osteoblast	O
+phenotype	O
+development	O
+.	O
+
+This	O
+model	O
+is	O
+further	O
+supported	O
+by	O
+binding	O
+of	O
+the	O
+Fos	B-GENE
+-	O
+Jun	B-GENE
+complex	O
+at	O
+an	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+in	O
+the	O
+type	B-GENE
+alpha	I-GENE
+I	I-GENE
+collagen	I-GENE
+promoter	I-GENE
+that	O
+is	O
+contiguous	O
+with	O
+,	O
+but	O
+not	O
+overlapping	O
+,	O
+the	O
+VDRE	O
+.	O
+
+PBSX	B-GENE
+is	O
+induced	O
+by	O
+agents	O
+which	O
+elicit	O
+the	O
+SOS	O
+response	O
+.	O
+
+A	O
+bacteriological	O
+relapse	O
+requiring	O
+treatment	O
+occurred	O
+by	O
+5	O
+years	O
+in	O
+16	O
+.	O
+8	O
+%	O
+of	O
+113	O
+R3	O
+,	O
+5	O
+.	O
+2	O
+%	O
+of	O
+97	O
+R5	O
+,	O
+and	O
+20	O
+.	O
+0	O
+%	O
+of	O
+115	O
+Z5	O
+patients	O
+with	O
+organisms	O
+sensitive	O
+to	O
+streptomycin	O
+and	O
+isoniazid	O
+initially	O
+.	O
+
+In	O
+the	O
+controls	O
+,	O
+it	O
+was	O
+found	O
+that	O
+all	O
+right	O
+-	O
+handed	O
+and	O
+10	O
+out	O
+of	O
+14	O
+left	O
+-	O
+handed	O
+control	O
+subjects	O
+showed	O
+a	O
+right	O
+VHF	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+left	O
+hemisphere	O
+)	O
+advantage	O
+.	O
+
+Although	O
+no	O
+Rh	B-GENE
+-	I-GENE
+antibodies	I-GENE
+were	O
+demonstrable	O
+,	O
+a	O
+similar	O
+mechanism	O
+can	O
+be	O
+postulated	O
+for	O
+the	O
+Rh	O
+-	O
+system	O
+.	O
+
+This	O
+study	O
+was	O
+performed	O
+to	O
+clarify	O
+the	O
+location	O
+of	O
+a	O
+transesophageal	O
+echocardiographic	O
+(	O
+TEE	O
+)	O
+transducer	O
+when	O
+obtaining	O
+the	O
+short	O
+-	O
+axis	O
+view	O
+of	O
+the	O
+left	O
+ventricle	O
+(	O
+S	O
+-	O
+LV	O
+)	O
+.	O
+
+From	O
+S3	O
+(	O
+CBF	O
+:	O
+79	O
+-	O
+60	O
+%	O
+)	O
+to	O
+S5	O
+(	O
+CBF	O
+:	O
+39	O
+-	O
+0	O
+%	O
+)	O
+,	O
+%	O
+WTh	O
+,	O
+1	O
+/	O
+TPC	O
+and	O
+1	O
+/	O
+T	O
+were	O
+significantly	O
+decreased	O
+from	O
+those	O
+of	O
+the	O
+control	O
+levels	O
+(	O
+all	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+In	O
+that	O
+case	O
+,	O
+the	O
+ratio	O
+of	O
+brush	O
+abrasion	O
+was	O
+0	O
+.	O
+268	O
+,	O
+compressive	O
+and	O
+transverse	O
+strength	O
+,	O
+124	O
+.	O
+3	O
+and	O
+86	O
+.	O
+3	O
+MPa	O
+respectively	O
+,	O
+hardness	O
+,	O
+43	O
+.	O
+2	O
+Hk	O
+,	O
+water	O
+absorption	O
+14	O
+.	O
+2	O
+micrograms	O
+/	O
+mm3	O
+and	O
+thermal	O
+expansion	O
+coefficient	O
+,	O
+47	O
+.	O
+4	O
+x	O
+10	O
+(	O
+-	O
+6	O
+)	O
+/	O
+degrees	O
+C	O
+.	O
+
+9	O
+,	O
+1498	O
+-	O
+1506	O
+)	O
+.	O
+
+In	O
+a	O
+highly	O
+select	O
+group	O
+of	O
+stable	O
+hypertensive	O
+patients	O
+,	O
+we	O
+have	O
+assessed	O
+the	O
+strength	O
+of	O
+association	O
+between	O
+various	O
+blood	O
+pressure	O
+measurements	O
+(	O
+24	O
+h	O
+average	O
+automated	O
+ambulatory	O
+blood	O
+pressure	O
+,	O
+4	O
+h	O
+automated	O
+ambulatory	O
+morning	O
+average	O
+blood	O
+pressure	O
+,	O
+multiple	O
+office	O
+visit	O
+average	O
+blood	O
+pressure	O
+,	O
+and	O
+a	O
+single	O
+office	O
+visit	O
+average	O
+blood	O
+pressure	O
+)	O
+and	O
+various	O
+echocardiographic	O
+indices	O
+of	O
+hypertensive	O
+cardiac	O
+target	O
+organ	O
+damage	O
+(	O
+left	O
+atrial	O
+diameter	O
+,	O
+left	O
+ventricular	O
+end	O
+diastolic	O
+diameter	O
+,	O
+posterior	O
+wall	O
+thickness	O
+,	O
+combined	O
+wall	O
+thickness	O
+,	O
+relative	O
+wall	O
+thickness	O
+,	O
+left	O
+ventricular	O
+mass	O
+and	O
+mass	O
+index	O
+,	O
+and	O
+combined	O
+wall	O
+thickness	O
+/	O
+left	O
+ventricular	O
+diastolic	O
+diameter	O
+ratio	O
+)	O
+.	O
+
+The	O
+p36	B-GENE
+gene	I-GENE
+is	O
+at	O
+least	O
+22	O
+kb	O
+in	O
+length	O
+and	O
+has	O
+a	O
+coding	O
+sequence	O
+of	O
+approximately	O
+1	O
+kb	O
+,	O
+representing	O
+only	O
+4	O
+.	O
+5	O
+%	O
+of	O
+the	O
+gene	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+This	O
+multimodality	O
+treatment	O
+for	O
+locally	O
+advanced	O
+gynecologic	O
+tumors	O
+appears	O
+feasible	O
+with	O
+modification	O
+,	O
+and	O
+continued	O
+work	O
+exploring	O
+this	O
+approach	O
+is	O
+encouraged	O
+.	O
+
+With	O
+the	O
+modified	O
+fingertip	O
+-	O
+to	O
+-	O
+floor	O
+(	O
+MFTF	O
+)	O
+method	O
+,	O
+patients	O
+stand	O
+on	O
+a	O
+stool	O
+and	O
+forward	O
+bend	O
+so	O
+that	O
+measurements	O
+can	O
+be	O
+taken	O
+on	O
+patients	O
+who	O
+are	O
+able	O
+to	O
+touch	O
+the	O
+floor	O
+or	O
+reach	O
+beyond	O
+the	O
+level	O
+of	O
+the	O
+floor	O
+.	O
+
+No	O
+significant	O
+differences	O
+could	O
+be	O
+seen	O
+in	O
+response	O
+rates	O
+according	O
+to	O
+the	O
+concentration	O
+of	O
+estrogen	B-GENE
+receptors	I-GENE
+or	O
+presence	O
+of	O
+progesteron	B-GENE
+receptors	I-GENE
+in	O
+this	O
+group	O
+of	O
+patients	O
+.	O
+
+Teicoplanin	O
+was	O
+given	O
+most	O
+often	O
+because	O
+of	O
+persistent	O
+fever	O
+or	O
+initial	O
+Gram	O
+-	O
+positive	O
+bacteraemia	O
+and	O
+only	O
+one	O
+-	O
+third	O
+of	O
+these	O
+cases	O
+responded	O
+.	O
+
+In	O
+Experiments	O
+1	O
+and	O
+2	O
+,	O
+infants	O
+,	O
+like	O
+adults	O
+,	O
+initially	O
+categorized	O
+novel	O
+objects	O
+on	O
+the	O
+basis	O
+of	O
+physical	O
+appearance	O
+,	O
+but	O
+only	O
+if	O
+trained	O
+with	O
+multiple	O
+exemplars	O
+,	O
+after	O
+delays	O
+of	O
+1	O
+and	O
+7	O
+days	O
+.	O
+
+The	O
+clinical	O
+picture	O
+of	O
+the	O
+disease	O
+was	O
+significantly	O
+different	O
+from	O
+anthropogenic	O
+cutaneous	O
+leishmaniasis	O
+caused	O
+by	O
+L	O
+.	O
+tropica	O
+but	O
+similar	O
+to	O
+cutaneous	O
+patterns	O
+caused	O
+by	O
+L	O
+.	O
+infantum	O
+which	O
+was	O
+a	O
+prevalent	O
+pattern	O
+in	O
+the	O
+southern	O
+France	O
+.	O
+
+In	O
+comparison	O
+with	O
+the	O
+16	O
+introns	O
+reported	O
+in	O
+AHA3	B-GENE
+,	O
+AHA2	B-GENE
+is	O
+missing	O
+one	O
+intron	O
+in	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+and	O
+a	O
+second	O
+intron	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+coding	O
+region	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+indicates	O
+that	O
+AHA2	B-GENE
+mRNA	I-GENE
+relative	O
+to	O
+total	O
+cellular	O
+RNA	O
+is	O
+expressed	O
+at	O
+significantly	O
+higher	O
+levels	O
+in	O
+root	O
+tissue	O
+as	O
+compared	O
+with	O
+shoot	O
+tissue	O
+.	O
+
+Impaction	O
+of	O
+gastrostomy	O
+tube	O
+in	O
+the	O
+abdominal	O
+wall	O
+.	O
+
+Both	O
+antidepressants	O
+elevated	O
+the	O
+pain	O
+threshold	O
+acutely	O
+,	O
+while	O
+pretreatment	O
+with	O
+pCPA	O
+largely	O
+blocked	O
+the	O
+analgesia	O
+.	O
+
+Sci	O
+.	O
+
+A	O
+needs	O
+assessment	O
+of	O
+these	O
+families	O
+was	O
+also	O
+done	O
+.	O
+
+TCR	B-GENE
+alpha	I-GENE
+and	I-GENE
+beta	I-GENE
+gene	I-GENE
+expression	O
+may	O
+be	O
+regulated	O
+by	O
+a	O
+common	O
+set	O
+of	O
+T	B-GENE
+-	I-GENE
+cell	I-GENE
+nuclear	I-GENE
+proteins	I-GENE
+in	O
+that	O
+the	O
+T	B-GENE
+beta	I-GENE
+2	I-GENE
+element	I-GENE
+binding	O
+a	O
+set	O
+of	O
+cyclic	B-GENE
+AMP	I-GENE
+response	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+that	O
+are	O
+also	O
+bound	O
+by	O
+the	O
+T	B-GENE
+alpha	I-GENE
+1	I-GENE
+element	I-GENE
+of	O
+the	O
+human	O
+TCR	B-GENE
+alpha	I-GENE
+enhancer	O
+and	O
+the	O
+decamer	O
+element	O
+present	O
+in	O
+a	O
+large	O
+number	O
+of	O
+human	O
+and	O
+murine	O
+TCR	B-GENE
+beta	I-GENE
+promoters	O
+.	O
+
+The	O
+3	O
+'	O
+stem	O
+-	O
+loop	O
+is	O
+highly	O
+divergent	O
+in	O
+structure	O
+among	O
+species	O
+and	O
+lies	O
+immediately	O
+upstream	O
+of	O
+the	O
+binding	O
+site	O
+for	O
+Sm	B-GENE
+proteins	I-GENE
+.	O
+
+The	O
+deleted	O
+nucleotide	O
+sequence	O
+corresponded	O
+to	O
+sequences	O
+that	O
+,	O
+by	O
+analogy	O
+to	O
+the	O
+organization	O
+of	O
+the	O
+type	B-GENE
+I	I-GENE
+collagen	I-GENE
+genes	I-GENE
+,	O
+should	O
+be	O
+precisely	O
+encoded	O
+by	O
+exon	O
+41	O
+of	O
+the	O
+COL3A1	B-GENE
+gene	I-GENE
+.	O
+
+These	O
+losses	O
+account	O
+for	O
+the	O
+resistance	O
+of	O
+EDS	O
+-	O
+IV	O
+collagen	B-GENE
+to	O
+cyanogen	O
+bromide	O
+and	O
+mammalian	B-GENE
+collagenase	I-GENE
+digestion	O
+.	O
+
+Two	O
+other	O
+peptides	O
+,	O
+either	O
+partially	O
+or	O
+totally	O
+lacking	O
+the	O
+basic	O
+region	O
+,	O
+but	O
+containing	O
+the	O
+intact	O
+leucine	O
+zipper	O
+domain	O
+,	O
+readily	O
+form	O
+dimers	O
+but	O
+do	O
+not	O
+bind	O
+to	O
+the	O
+CRE	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+CRE	O
+of	O
+the	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+fos	I-GENE
+promoter	I-GENE
+located	O
+at	O
+-	O
+60	O
+was	O
+weakly	O
+induced	O
+by	O
+cAMP	O
+and	O
+E1a	B-GENE
+in	O
+both	O
+HeLa	O
+and	O
+PC12	O
+cells	O
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+sequenced	O
+the	O
+gene	O
+encoding	O
+the	O
+human	B-GENE
+U1	I-GENE
+-	I-GENE
+70K	I-GENE
+snRNP	I-GENE
+protein	I-GENE
+.	O
+
+Although	O
+popular	O
+this	O
+hypothesis	O
+is	O
+far	O
+from	O
+explaining	O
+all	O
+the	O
+clinical	O
+facts	O
+,	O
+namely	O
+that	O
+rigidity	O
+is	O
+equal	O
+in	O
+extensor	O
+and	O
+flexor	O
+,	O
+proximal	O
+and	O
+distal	O
+muscles	O
+.	O
+
+Fluid	O
+(	O
+AVLF	O
+)	O
+31	O
+.	O
+
+The	O
+results	O
+supported	O
+the	O
+therapeutic	O
+principle	O
+of	O
+TCM	O
+:	O
+Treating	O
+patients	O
+according	O
+to	O
+their	O
+pathophysiological	O
+patterns	O
+.	O
+
+The	O
+nmr	B-GENE
+gene	I-GENE
+is	O
+the	O
+major	O
+negative	O
+regulatory	O
+gene	O
+in	O
+the	O
+nitrogen	O
+control	O
+circuit	O
+of	O
+Neurospora	O
+crassa	O
+,	O
+which	O
+,	O
+together	O
+with	O
+positive	O
+regulatory	O
+genes	O
+,	O
+governs	O
+the	O
+expression	O
+of	O
+multiple	O
+unlinked	O
+structural	O
+genes	O
+of	O
+the	O
+circuit	O
+.	O
+
+The	O
+4	O
+days	O
+dexamethasone	O
+suppression	O
+test	O
+showed	O
+more	O
+than	O
+80	O
+%	O
+suppression	O
+of	O
+dehydroepiandrosterone	O
+-	O
+sulphate	O
+and	O
+a	O
+variable	O
+(	O
+40	O
+-	O
+60	O
+%	O
+)	O
+reduction	O
+of	O
+testosterone	O
+and	O
+androstenedione	O
+levels	O
+.	O
+
+The	O
+ratio	O
+of	O
+P	O
+-	O
+31	O
+NMR	O
+-	O
+S	O
+derived	O
+inorganic	O
+phosphates	O
+[	O
+Pi	O
+]	O
+to	O
+phosphocreatine	O
+[	O
+PCr	O
+]	O
+was	O
+significantly	O
+greater	O
+at	O
+rest	O
+in	O
+LVH	O
+baboons	O
+[	O
+0	O
+.	O
+53	O
++	O
+/	O
+-	O
+0	O
+.	O
+06	O
+versus	O
+controls	O
+=	O
+0	O
+.	O
+41	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+;	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+]	O
+.	O
+
+Cutaneous	O
+necrosis	O
+associated	O
+with	O
+protein	B-GENE
+S	I-GENE
+deficiency	O
+.	O
+
+Critical	O
+study	O
+
+Regional	O
+cerebral	O
+blood	O
+flow	O
+was	O
+measured	O
+using	O
+N	O
+-	O
+isopropyl	O
+-	O
+123I	O
+-	O
+iodoamphetamine	O
+with	O
+single	O
+-	O
+photon	O
+emission	O
+computed	O
+tomography	O
+(	O
+CT	O
+)	O
+in	O
+16	O
+aged	O
+patients	O
+with	O
+noninsulin	O
+-	O
+dependent	O
+diabetes	O
+mellitus	O
+(	O
+NIDDM	O
+,	O
+average	O
+age	O
+72	O
+.	O
+8	O
+years	O
+,	O
+average	O
+fasting	O
+plasma	O
+glucose	O
+7	O
+.	O
+7	O
+mmol	O
+/	O
+L	O
+)	O
+,	O
+and	O
+12	O
+nondiabetic	O
+subjects	O
+(	O
+71	O
+.	O
+6	O
+years	O
+,	O
+5	O
+.	O
+3	O
+mmol	O
+/	O
+L	O
+)	O
+.	O
+
+Mean	O
+ROI	O
+-	O
+A	O
+/	O
+B	O
+ratio	O
+was	O
+49	O
+.	O
+6	O
++	O
+/	O
+-	O
+1	O
+.	O
+7	O
+%	O
+in	O
+the	O
+diabetic	O
+group	O
+,	O
+significantly	O
+lower	O
+than	O
+the	O
+57	O
+.	O
+9	O
++	O
+/	O
+-	O
+1	O
+.	O
+6	O
+%	O
+at	O
+the	O
+nondiabetic	O
+group	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+005	O
+)	O
+.	O
+
+These	O
+data	O
+strongly	O
+implicate	O
+the	O
+normal	O
+product	O
+of	O
+the	O
+int	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+,	O
+which	O
+is	O
+related	O
+to	O
+the	O
+fibroblast	B-GENE
+growth	I-GENE
+factor	I-GENE
+family	I-GENE
+,	O
+as	O
+a	O
+contributory	O
+factor	O
+in	O
+virally	O
+induced	O
+mammary	O
+tumors	O
+.	O
+
+The	O
+PC2	B-GENE
+protein	I-GENE
+also	O
+shows	O
+great	O
+similarity	O
+to	O
+the	O
+incomplete	O
+NH2	O
+-	O
+terminal	O
+sequence	O
+of	O
+the	O
+human	B-GENE
+furin	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+a	O
+putative	O
+membrane	O
+-	O
+inserted	O
+receptor	O
+-	O
+like	O
+molecule	O
+.	O
+
+Whether	O
+or	O
+not	O
+there	O
+are	O
+sequences	O
+conferring	O
+cAMP	O
+responsiveness	O
+which	O
+are	O
+common	O
+both	O
+to	O
+P	B-GENE
+-	I-GENE
+450scc	I-GENE
+and	O
+the	O
+other	O
+steroidogenic	O
+P	B-GENE
+-	I-GENE
+450	I-GENE
+genes	I-GENE
+remains	O
+to	O
+be	O
+established	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+used	O
+footprinting	O
+and	O
+gel	O
+mobility	O
+retardation	O
+assays	O
+to	O
+reveal	O
+that	O
+bacterially	O
+synthesized	O
+Zta	B-GENE
+fusion	I-GENE
+proteins	I-GENE
+bound	O
+directly	O
+to	O
+six	O
+TGTGCAA	O
+-	O
+like	O
+motifs	O
+within	O
+DSL	B-GENE
+.	O
+
+The	O
+zta	B-GENE
+transactivator	I-GENE
+involved	O
+in	O
+induction	O
+of	O
+lytic	O
+cycle	O
+gene	O
+expression	O
+in	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+-	O
+infected	O
+lymphocytes	O
+binds	O
+to	O
+both	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+ZRE	B-GENE
+sites	I-GENE
+in	O
+target	O
+promoter	O
+and	O
+enhancer	O
+regions	O
+.	O
+
+It	O
+is	O
+the	O
+human	O
+homolog	O
+of	O
+the	O
+mouse	B-GENE
+Mx	I-GENE
+protein	I-GENE
+involved	O
+in	O
+resistance	O
+to	O
+influenza	O
+virus	O
+.	O
+
+Fragments	O
+containing	O
+the	O
+21	O
+-	O
+base	O
+-	O
+pair	O
+repeat	O
+region	O
+,	O
+the	O
+enhancer	B-GENE
+of	I-GENE
+simian	I-GENE
+virus	I-GENE
+40	I-GENE
+or	O
+both	O
+strongly	O
+stimulated	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+synthesis	O
+,	O
+and	O
+three	O
+fragments	O
+from	O
+the	O
+polyomavirus	B-GENE
+enhancer	I-GENE
+region	I-GENE
+stimulated	O
+moderate	O
+levels	O
+.	O
+
+The	O
+sites	O
+targeted	O
+for	O
+mutagenesis	O
+,	O
+residues	O
+60	O
+,	O
+61	O
+,	O
+and	O
+66	O
+,	O
+are	O
+located	O
+within	O
+a	O
+putative	O
+helical	O
+loop	O
+structure	O
+which	O
+may	O
+be	O
+involved	O
+in	O
+substrate	O
+recognition	O
+by	O
+the	O
+enzyme	O
+.	O
+
+The	O
+possible	O
+benefits	O
+of	O
+LMW	O
+heparin	O
+(	O
+reduced	O
+frequency	O
+of	O
+bleeding	O
+,	O
+alleviation	O
+of	O
+hypertriglyceridemia	O
+)	O
+were	O
+not	O
+,	O
+however	O
+,	O
+apparent	O
+,	O
+possibly	O
+because	O
+of	O
+the	O
+short	O
+observation	O
+period	O
+and	O
+the	O
+low	O
+incidence	O
+of	O
+hemorrhagic	O
+complications	O
+in	O
+routine	O
+dialyses	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+destrin	B-GENE
+is	O
+165	O
+residues	O
+long	O
+and	O
+is	O
+very	O
+similar	O
+(	O
+71	O
+%	O
+identical	O
+)	O
+to	O
+that	O
+of	O
+cofilin	B-GENE
+,	O
+a	O
+widely	O
+distributed	O
+,	O
+pH	O
+-	O
+sensitive	O
+actin	B-GENE
+-	O
+modulating	O
+protein	O
+.	O
+
+Summers	O
+,	O
+Virology	O
+89	O
+:	O
+517	O
+-	O
+527	O
+,	O
+1978	O
+)	O
+.	O
+
+With	O
+only	O
+purified	O
+T	B-GENE
+antigen	I-GENE
+in	O
+the	O
+presence	O
+of	O
+topoisomerase	B-GENE
+I	I-GENE
+to	O
+unwind	O
+purified	O
+DNA	O
+,	O
+ori	O
+-	O
+auxiliary	O
+sequences	O
+strongly	O
+facilitated	O
+T	B-GENE
+-	I-GENE
+antigen	I-GENE
+-	O
+dependent	O
+DNA	O
+conformational	O
+changes	O
+consistent	O
+with	O
+melting	O
+the	O
+first	O
+50	O
+base	O
+pairs	O
+.	O
+
+A	O
+rabbit	O
+antiserum	O
+was	O
+raised	O
+against	O
+a	O
+synthetic	O
+peptide	O
+corresponding	O
+to	O
+a	O
+hydrophilic	O
+portion	O
+of	O
+the	O
+translated	O
+murine	O
+cDNA	O
+sequence	O
+.	O
+
+Conservation	O
+of	O
+function	O
+of	O
+Drosophila	B-GENE
+melanogaster	I-GENE
+abl	I-GENE
+and	O
+murine	B-GENE
+v	I-GENE
+-	I-GENE
+abl	I-GENE
+proteins	I-GENE
+in	O
+transformation	O
+of	O
+mammalian	O
+cells	O
+.	O
+
+Specific	O
+binding	O
+of	O
+the	O
+protein	O
+factors	O
+to	O
+the	O
+sites	O
+,	O
+possibly	O
+to	O
+the	O
+three	O
+Mt	O
+sequences	O
+,	O
+may	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+coordinate	O
+regulation	O
+of	O
+the	O
+transcription	O
+of	O
+nuclear	O
+genes	O
+encoding	O
+subunits	O
+responsible	O
+for	O
+mitochondrial	O
+oxidative	O
+phosphorylation	O
+.	O
+
+This	O
+points	O
+to	O
+a	O
+specific	O
+interference	O
+with	O
+HSV	O
+-	O
+induced	O
+DNA	O
+amplification	O
+.	O
+
+Constructs	O
+were	O
+made	O
+in	O
+which	O
+an	O
+AATAAA	O
+and	O
+the	O
+GT	O
+-	O
+rich	O
+region	O
+were	O
+separated	O
+by	O
+various	O
+distances	O
+ranging	O
+from	O
+7	O
+to	O
+43	O
+bp	O
+.	O
+
+To	O
+address	O
+this	O
+issue	O
+,	O
+the	O
+gene	O
+for	O
+factor	B-GENE
+Y	I-GENE
+has	O
+been	O
+cloned	O
+molecularly	O
+and	O
+its	O
+DNA	O
+sequence	O
+has	O
+been	O
+determined	O
+.	O
+
+We	O
+cloned	O
+and	O
+sequenced	O
+the	O
+cDNAs	O
+against	O
+genomic	O
+RNA	O
+and	O
+mRNA	O
+for	O
+phosphoprotein	B-GENE
+(	I-GENE
+P	I-GENE
+)	I-GENE
+of	O
+human	O
+parainfluenza	O
+type	O
+2	O
+virus	O
+(	O
+PIV	O
+-	O
+2	O
+)	O
+.	O
+cDNA	O
+clone	O
+from	O
+genomic	O
+RNA	O
+was	O
+1439	O
+nucleotides	O
+in	O
+length	O
+excluding	O
+poly	O
+(	O
+A	O
+)	O
+and	O
+was	O
+found	O
+to	O
+have	O
+two	O
+small	O
+open	O
+reading	O
+frames	O
+encoding	O
+proteins	O
+of	O
+233	O
+and	O
+249	O
+amino	O
+acids	O
+.	O
+
+We	O
+show	O
+that	O
+cytR	B-GENE
+expression	O
+is	O
+negatively	O
+controlled	O
+by	O
+the	O
+CytR	B-GENE
+protein	I-GENE
+and	O
+positively	O
+affected	O
+by	O
+the	O
+cAMP	B-GENE
+/	I-GENE
+CAP	I-GENE
+complex	I-GENE
+.	O
+
+The	O
+cDNA	O
+sequence	O
+has	O
+an	O
+813	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+(	O
+ORF	O
+)	O
+whose	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+is	O
+97	O
+.	O
+6	O
+%	O
+identical	O
+to	O
+the	O
+272	O
+carboxy	O
+-	O
+terminal	O
+amino	O
+acids	O
+of	O
+the	O
+human	B-GENE
+ets	I-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+.	O
+
+To	O
+characterize	O
+the	O
+O7	B-GENE
+-	I-GENE
+LPS	I-GENE
+region	I-GENE
+,	O
+the	O
+recombinant	O
+cosmids	O
+pJHCV31	O
+and	O
+pJHCV32	O
+were	O
+mutagenized	O
+by	O
+transposon	O
+mutagenesis	O
+with	O
+Tn3HoHo1	B-GENE
+,	O
+which	O
+carries	O
+a	O
+promoterless	O
+lac	B-GENE
+operon	I-GENE
+and	O
+can	O
+therefore	O
+generate	O
+lacZ	B-GENE
+transcriptional	O
+fusions	O
+with	O
+target	O
+DNA	O
+sequences	O
+.	O
+
+The	O
+sacT	B-GENE
+gene	I-GENE
+regulating	O
+the	O
+sacPA	B-GENE
+operon	I-GENE
+in	I-GENE
+Bacillus	I-GENE
+subtilis	I-GENE
+shares	O
+strong	O
+homology	O
+with	O
+transcriptional	O
+antiterminators	O
+.	O
+
+Various	O
+mutant	B-GENE
+HN	I-GENE
+genes	I-GENE
+were	O
+constructed	O
+to	O
+examine	O
+the	O
+role	O
+of	O
+residues	O
+flanking	O
+the	O
+signal	O
+-	O
+anchor	O
+domain	O
+,	O
+including	O
+the	O
+cytoplasmic	O
+tail	O
+,	O
+on	O
+assembly	O
+and	O
+intracellular	O
+transport	O
+of	O
+the	O
+HN	B-GENE
+glycoprotein	I-GENE
+.	O
+
+Our	O
+studies	O
+extend	O
+these	O
+findings	O
+and	O
+show	O
+that	O
+the	O
+E2	B-GENE
+transactivation	I-GENE
+gene	I-GENE
+is	O
+expressed	O
+from	O
+multiple	O
+promoters	O
+.	O
+
+Furthermore	O
+,	O
+analysis	O
+of	O
+the	O
+E2	B-GENE
+proteins	I-GENE
+present	O
+in	O
+various	O
+cell	O
+lines	O
+harboring	O
+specific	O
+BPV	O
+-	O
+1	O
+mutants	O
+,	O
+including	O
+the	O
+2558	O
+acceptor	O
+mutant	O
+,	O
+proves	O
+that	O
+alternate	O
+modes	O
+of	O
+E2	B-GENE
+expression	O
+exist	O
+.	O
+
+Disruption	O
+of	O
+the	O
+IRA2	B-GENE
+gene	I-GENE
+resulted	O
+in	O
+(	O
+i	O
+)	O
+increased	O
+sensitivity	O
+to	O
+heat	O
+shock	O
+and	O
+nitrogen	O
+starvation	O
+,	O
+(	O
+ii	O
+)	O
+sporulation	O
+defects	O
+,	O
+and	O
+(	O
+iii	O
+)	O
+suppression	O
+of	O
+the	O
+lethality	O
+of	O
+the	O
+cdc25	B-GENE
+mutant	I-GENE
+.	O
+
+This	O
+cohort	O
+of	O
+patients	O
+was	O
+selected	O
+on	O
+the	O
+basis	O
+of	O
+clinical	O
+stage	O
+.	O
+
+The	O
+diagnosis	O
+of	O
+miliary	O
+tuberculosis	O
+should	O
+be	O
+systematically	O
+considered	O
+in	O
+ARDS	O
+of	O
+unknown	O
+origin	O
+.	O
+
+In	O
+order	O
+to	O
+characterize	O
+the	O
+functional	O
+elements	O
+of	O
+the	O
+promoter	O
+that	O
+in	O
+some	O
+way	O
+must	O
+respond	O
+to	O
+these	O
+regulatory	O
+signals	O
+,	O
+a	O
+number	O
+of	O
+promoter	O
+mutations	O
+were	O
+constructed	O
+,	O
+including	O
+a	O
+set	O
+of	O
+linker	O
+-	O
+scanning	O
+mutations	O
+across	O
+the	O
+entire	O
+promoter	O
+region	O
+.	O
+
+A	O
+DNA	O
+motif	O
+related	O
+to	O
+the	O
+cAMP	O
+-	O
+responsive	O
+element	O
+and	O
+an	O
+exon	B-GENE
+-	I-GENE
+located	I-GENE
+activator	I-GENE
+protein	I-GENE
+-	I-GENE
+2	I-GENE
+binding	I-GENE
+site	I-GENE
+in	O
+the	O
+human	B-GENE
+tissue	I-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+gene	I-GENE
+promoter	I-GENE
+cooperate	O
+in	O
+basal	O
+expression	O
+and	O
+convey	O
+activation	O
+by	O
+phorbol	O
+ester	O
+and	O
+cAMP	O
+.	O
+
+The	O
+26S	B-GENE
+rRNA	I-GENE
+binding	I-GENE
+ribosomal	I-GENE
+protein	I-GENE
+equivalent	O
+to	O
+bacterial	B-GENE
+protein	I-GENE
+L11	I-GENE
+is	O
+encoded	O
+by	O
+unspliced	O
+duplicated	O
+genes	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Five	O
+healthy	O
+male	O
+subjects	O
+inspired	O
+air	O
+for	O
+20	O
+min	O
+and	O
+then	O
+5	O
+%	O
+CO2	O
+/	O
+95	O
+%	O
+O2	O
+for	O
+30	O
+min	O
+,	O
+of	O
+which	O
+the	O
+first	O
+10	O
+min	O
+was	O
+used	O
+to	O
+achieve	O
+a	O
+steady	O
+-	O
+state	O
+end	O
+-	O
+tidal	O
+CO2	O
+measurement	O
+.	O
+
+The	O
+transcripts	O
+were	O
+equally	O
+active	O
+with	O
+or	O
+without	O
+a	O
+5	O
+'	O
+methylated	O
+capstructure	O
+as	O
+expected	O
+,	O
+since	O
+EMCV	O
+-	O
+RNA	O
+is	O
+one	O
+of	O
+the	O
+mRNAs	O
+capable	O
+of	O
+internal	O
+initiation	O
+.	O
+
+The	O
+E6	B-GENE
+/	O
+E7	B-GENE
+promoter	O
+of	O
+all	O
+genital	O
+human	O
+papillomaviruses	O
+is	O
+responsible	O
+for	O
+expression	O
+of	O
+the	O
+viral	O
+transforming	O
+genes	O
+.	O
+
+A	O
+case	O
+of	O
+Goodpasture	O
+'	O
+s	O
+syndrome	O
+.	O
+
+Seventy	O
+-	O
+two	O
+of	O
+73	O
+negative	O
+controls	O
+and	O
+all	O
+positive	O
+blocks	O
+as	O
+seen	O
+on	O
+soft	O
+tissue	O
+radiographs	O
+(	O
+STRs	O
+)	O
+were	O
+correctly	O
+coded	O
+(	O
+specificity	O
+98	O
+.	O
+6	O
+%	O
+,	O
+sensitivity	O
+100	O
+%	O
+)	O
+.	O
+
+No	O
+symptomatic	O
+abnormality	O
+has	O
+been	O
+noted	O
+in	O
+the	O
+neonatal	O
+period	O
+except	O
+periventricular	O
+calcifications	O
+.	O
+
+Immunohistochemical	O
+analysis	O
+of	O
+several	O
+rat	O
+organs	O
+also	O
+showed	O
+staining	O
+in	O
+epithelial	O
+cells	O
+.	O
+
+Transcription	O
+of	O
+the	O
+first	O
+operon	O
+coding	O
+for	O
+m	O
+-	O
+xylene	O
+-	O
+degrading	O
+enzymes	O
+on	O
+the	O
+TOL	O
+plasmid	O
+of	O
+Pseudomonas	O
+putida	O
+is	O
+activated	O
+by	O
+the	O
+xylR	B-GENE
+gene	I-GENE
+product	I-GENE
+in	O
+the	O
+presence	O
+of	O
+m	O
+-	O
+xylene	O
+.	O
+
+Some	O
+of	O
+the	O
+mutations	O
+obtained	O
+do	O
+not	O
+contain	O
+a	O
+copy	O
+of	O
+the	O
+Ulysses	B-GENE
+element	I-GENE
+at	O
+the	O
+mutant	O
+locus	O
+,	O
+suggesting	O
+that	O
+a	O
+different	O
+transposable	O
+element	O
+may	O
+be	O
+responsible	O
+for	O
+the	O
+mutation	O
+.	O
+
+Determination	O
+of	O
+diquat	O
+in	O
+biological	O
+materials	O
+by	O
+electron	O
+spin	O
+resonance	O
+spectroscopy	O
+.	O
+
+We	O
+show	O
+also	O
+that	O
+RA	O
+represses	O
+the	O
+transcriptional	O
+activity	O
+of	O
+a	O
+reporter	O
+gene	O
+containing	O
+a	O
+TPA	O
+responding	O
+AP1	B-GENE
+binding	I-GENE
+site	I-GENE
+driving	O
+the	O
+HSV	B-GENE
+tk	I-GENE
+promoter	I-GENE
+.	O
+
+Moreover	O
+,	O
+radiolabeled	O
+EFI	B-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+,	O
+or	O
+CBF	B-GENE
+DNAs	I-GENE
+give	O
+rise	O
+to	O
+identical	O
+gel	O
+retardation	O
+patterns	O
+in	O
+extracts	O
+from	O
+a	O
+variety	O
+of	O
+different	O
+cell	O
+types	O
+.	O
+
+Risk	O
+factors	O
+influencing	O
+lymph	O
+nodes	O
+metastasis	O
+in	O
+lung	O
+cancer	O
+with	O
+stage	O
+I	O
+,	O
+II	O
+or	O
+IIIA	O
+
+Multifunctional	B-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+MFPK	B-GENE
+)	O
+phosphorylates	O
+ATP	B-GENE
+-	I-GENE
+citrate	I-GENE
+lyase	I-GENE
+on	O
+peptide	B-GENE
+B	I-GENE
+on	O
+two	O
+sites	O
+,	O
+BT	O
+and	O
+BS	O
+,	O
+on	O
+threonine	O
+and	O
+serine	O
+,	O
+respectively	O
+,	O
+inhibitor	B-GENE
+2	I-GENE
+on	O
+a	O
+threonyl	O
+residue	O
+,	O
+and	O
+glycogen	B-GENE
+synthase	I-GENE
+at	O
+sites	O
+2	O
+and	O
+3	O
+.	O
+
+The	O
+electrically	O
+induced	O
+motile	O
+responses	O
+were	O
+not	O
+suppressed	O
+in	O
+the	O
+presence	O
+of	O
+dinitrophenol	O
+or	O
+cytochalasin	O
+B	O
+.	O
+
+Unlike	O
+p59v	B-GENE
+-	O
+rel	B-GENE
+,	O
+which	O
+is	O
+a	O
+nuclear	O
+protein	O
+in	O
+CEF	O
+,	O
+indirect	O
+immunofluorescence	O
+showed	O
+that	O
+p68c	B-GENE
+-	O
+rel	B-GENE
+in	O
+JD214c	O
+-	O
+rel	O
+infected	O
+CEF	O
+is	O
+located	O
+exclusively	O
+in	O
+the	O
+cytoplasm	O
+of	O
+these	O
+cells	O
+,	O
+even	O
+though	O
+the	O
+sequence	O
+of	O
+p68c	B-GENE
+-	O
+rel	B-GENE
+showed	O
+that	O
+it	O
+contains	O
+a	O
+nuclear	O
+localizing	O
+sequence	O
+identical	O
+to	O
+the	O
+one	O
+previously	O
+identified	O
+in	O
+p59v	B-GENE
+-	O
+rel	B-GENE
+.	O
+
+Kinetic	O
+experiments	O
+revealed	O
+that	O
+within	O
+10	O
+min	O
+this	O
+radiolabeled	O
+precursor	O
+protein	O
+was	O
+converted	O
+in	O
+HL	O
+-	O
+60	O
+cells	O
+into	O
+an	O
+Mr	O
+approximately	O
+150	O
+,	O
+000	O
+chondroitin	O
+sulfate	O
+proteoglycan	O
+intermediate	O
+.	O
+
+Blood	O
+flow	O
+and	O
+velocity	O
+(	O
+measured	O
+using	O
+Doppler	O
+ultrasound	O
+)	O
+gradually	O
+decreased	O
+during	O
+diastole	O
+and	O
+ultimately	O
+reversed	O
+in	O
+direction	O
+as	O
+cotyledon	O
+resistance	O
+was	O
+increased	O
+up	O
+to	O
+14	O
+fold	O
+.	O
+
+A	O
+total	O
+of	O
+112	O
+patients	O
+received	O
+anistreplase	O
+and	O
+119	O
+received	O
+heparin	O
+within	O
+a	O
+mean	O
+period	O
+of	O
+188	O
++	O
+/	O
+-	O
+62	O
+min	O
+following	O
+the	O
+onset	O
+of	O
+symptoms	O
+.	O
+
+The	O
+promoter	O
+activity	O
+was	O
+measured	O
+by	O
+a	O
+transient	O
+expression	O
+of	O
+a	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+gene	O
+connected	O
+with	O
+various	O
+5	O
+'	O
+-	O
+deletion	O
+mutants	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+.	O
+
+The	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+14DM	I-GENE
+gene	I-GENE
+,	O
+encoding	O
+cytochrome	B-GENE
+P450	I-GENE
+lanosterol	I-GENE
+14	I-GENE
+alpha	I-GENE
+-	I-GENE
+demethylase	I-GENE
+(	O
+14DM	B-GENE
+)	O
+,	O
+was	O
+overexpressed	O
+in	O
+various	O
+S	O
+.	O
+cerevisiae	O
+strains	O
+under	O
+the	O
+control	O
+of	O
+three	O
+strong	O
+heterologous	O
+yeast	O
+transcription	O
+promoters	O
+(	O
+pADC1	B-GENE
+,	O
+pGPD	B-GENE
+,	O
+pPHO5	B-GENE
+)	O
+and	O
+under	O
+the	O
+control	O
+of	O
+its	O
+own	O
+promoter	O
+.	O
+
+Truncations	O
+composed	O
+of	O
+78	O
+and	O
+64	O
+amino	O
+acids	O
+were	O
+translocated	O
+across	O
+the	O
+endoplasmic	O
+reticulum	O
+membrane	O
+,	O
+and	O
+translocation	O
+was	O
+found	O
+to	O
+be	O
+strictly	O
+co	O
+-	O
+translational	O
+and	O
+SRP	B-GENE
+-	O
+dependent	O
+.	O
+
+Pulmonary	O
+vascular	O
+resistance	O
+was	O
+not	O
+altered	O
+,	O
+ejection	O
+fraction	O
+remained	O
+unchanged	O
+and	O
+isovolumic	O
+relaxation	O
+period	O
+was	O
+lengthened	O
+(	O
+119	O
++	O
+/	O
+-	O
+20	O
+.	O
+1	O
+to	O
+147	O
+.	O
+39	O
++	O
+/	O
+-	O
+21	O
+.	O
+15	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+ANB1	B-GENE
+locus	I-GENE
+of	O
+Saccharomyces	O
+cerevisiae	O
+encodes	O
+the	O
+protein	B-GENE
+synthesis	I-GENE
+initiation	I-GENE
+factor	I-GENE
+eIF	I-GENE
+-	I-GENE
+4D	I-GENE
+.	O
+
+Serum	B-GENE
+beta	I-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+levels	O
+(	O
+beta	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+M	I-GENE
+)	O
+were	O
+studied	O
+in	O
+150	O
+drug	O
+addicts	O
+,	O
+50	O
+of	O
+them	O
+asymptomatic	O
+carriers	O
+of	O
+anti	B-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+antibodies	I-GENE
+,	O
+50	O
+symptomatic	O
+carriers	O
+with	O
+persistent	O
+generalized	O
+lymphadenopathy	O
+(	O
+P	O
+.	O
+G	O
+.	O
+L	O
+.	O
+)	O
+and	O
+50	O
+serum	O
+negative	O
+patients	O
+who	O
+had	O
+been	O
+living	O
+in	O
+a	O
+closed	O
+community	O
+for	O
+at	O
+least	O
+2	O
+years	O
+.	O
+
+This	O
+emancipation	O
+of	O
+the	O
+ability	O
+to	O
+copulate	O
+from	O
+hormonal	O
+influence	O
+makes	O
+female	O
+sexual	O
+motivation	O
+the	O
+primary	O
+regulator	O
+of	O
+mating	O
+in	O
+primates	O
+.	O
+
+No	O
+therapy	O
+exists	O
+for	O
+halting	O
+the	O
+progression	O
+of	O
+the	O
+disease	O
+with	O
+the	O
+possible	O
+exception	O
+of	O
+laser	O
+photocoagulation	O
+treatment	O
+used	O
+to	O
+ablate	O
+subretinal	O
+neovascular	O
+membranes	O
+in	O
+an	O
+attempt	O
+to	O
+avoid	O
+complications	O
+of	O
+subretinal	O
+hemorrhages	O
+.	O
+
+R	O
+.	O
+
+Specific	O
+hyperimmune	B-GENE
+globulins	I-GENE
+to	O
+pathogens	O
+such	O
+as	O
+Haemophilus	O
+influenzae	O
+and	O
+Streptococcus	O
+pneumoniae	O
+have	O
+also	O
+been	O
+studied	O
+.	O
+
+Therapeutic	O
+effects	O
+of	O
+cefpirome	O
+(	O
+HR	O
+810	O
+)	O
+on	O
+experimental	O
+mixed	O
+infections	O
+with	O
+Enterococcus	O
+faecalis	O
+and	O
+Escherichia	O
+coli	O
+in	O
+mice	O
+.	O
+
+Regulation	O
+of	O
+yeast	B-GENE
+LEU2	I-GENE
+.	O
+
+Homozygous	O
+individuals	O
+usually	O
+develop	O
+purpura	O
+fulminans	O
+as	O
+newborns	O
+;	O
+heterozygous	O
+protein	B-GENE
+C	I-GENE
+-	O
+deficient	O
+individuals	O
+are	O
+at	O
+increased	O
+risk	O
+for	O
+venous	O
+thrombosis	O
+and	O
+pulmonary	O
+embolism	O
+.	O
+
+Ischemic	O
+stroke	O
+due	O
+to	O
+protein	B-GENE
+C	I-GENE
+deficiency	O
+.	O
+
+TREB7	B-GENE
+and	O
+TREB36	B-GENE
+protected	O
+all	O
+three	O
+repeats	O
+of	O
+the	O
+21	O
+bp	O
+,	O
+but	O
+TREB5	B-GENE
+protected	O
+only	O
+the	O
+second	O
+repeat	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+5	O
+KE	O
+X	O
+3	O
+/	O
+W	O
+may	O
+be	O
+the	O
+optimal	O
+regimen	O
+to	O
+augment	O
+the	O
+antitumor	O
+immunity	O
+of	O
+RNL	O
+.	O
+
+Analysis	O
+of	O
+various	O
+deletion	O
+mutants	O
+indicates	O
+that	O
+the	O
+sequence	O
+requirements	O
+for	O
+binding	O
+by	O
+QBP	B-GENE
+in	O
+vitro	O
+are	O
+indistinguishable	O
+from	O
+those	O
+necessary	O
+for	O
+Q	O
+activity	O
+in	O
+vivo	O
+,	O
+strongly	O
+suggesting	O
+that	O
+QBP	B-GENE
+is	O
+required	O
+for	O
+the	O
+function	O
+of	O
+this	O
+TATA	O
+-	O
+independent	O
+promoter	O
+.	O
+
+Since	O
+general	B-GENE
+regulatory	I-GENE
+factor	I-GENE
+I	I-GENE
+(	O
+GRFI	B-GENE
+)	O
+/	O
+repressor	B-GENE
+/	I-GENE
+activator	I-GENE
+site	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+(	O
+RAP1	B-GENE
+)	O
+/	O
+translation	B-GENE
+upstream	I-GENE
+factor	I-GENE
+(	O
+TUF	B-GENE
+)	O
+is	O
+believed	O
+to	O
+be	O
+an	O
+activator	O
+of	O
+MAT	B-GENE
+alpha	I-GENE
+expression	O
+,	O
+we	O
+examined	O
+whether	O
+PYK1	B-GENE
+,	O
+which	O
+is	O
+known	O
+to	O
+be	O
+regulated	O
+by	O
+GRFI	B-GENE
+/	O
+RAP1	B-GENE
+/	O
+TUF	B-GENE
+,	O
+is	O
+also	O
+affected	O
+by	O
+the	O
+gal11	B-GENE
+mutation	I-GENE
+.	O
+
+Yeast	B-GENE
+Gal11	I-GENE
+protein	I-GENE
+mediates	O
+the	O
+transcriptional	O
+activation	O
+signal	O
+of	O
+two	O
+different	O
+transacting	O
+factors	O
+,	O
+Gal4	B-GENE
+and	O
+general	B-GENE
+regulatory	I-GENE
+factor	I-GENE
+I	I-GENE
+/	O
+repressor	B-GENE
+/	I-GENE
+activator	I-GENE
+site	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+/	O
+translation	B-GENE
+upstream	I-GENE
+factor	I-GENE
+.	O
+
+Deletion	O
+from	O
+either	O
+the	O
+N	O
+-	O
+or	O
+C	O
+-	O
+terminal	O
+ends	O
+of	O
+repA	B-GENE
+(	O
+28	O
+and	O
+69	O
+codons	O
+,	O
+respectively	O
+,	O
+out	O
+of	O
+the	O
+286	O
+-	O
+codon	O
+open	O
+reading	O
+frame	O
+)	O
+affected	O
+the	O
+initiator	O
+but	O
+not	O
+the	O
+inhibitory	O
+activity	O
+.	O
+
+The	O
+two	O
+larger	O
+peptides	O
+,	O
+one	O
+containing	O
+amino	O
+acids	O
+1	O
+-	O
+228	O
+and	O
+the	O
+other	O
+containing	O
+amino	O
+acids	O
+85	O
+-	O
+228	O
+,	O
+formed	O
+dimers	O
+in	O
+solution	O
+and	O
+bound	O
+DNA	O
+specifically	O
+as	O
+a	O
+dimer	O
+.	O
+
+In	O
+vitro	O
+transcription	O
+extracts	O
+from	O
+ret1	B-GENE
+-	I-GENE
+1	I-GENE
+cells	O
+terminate	O
+less	O
+efficiently	O
+at	O
+weak	O
+transcription	O
+termination	O
+signals	O
+than	O
+those	O
+from	O
+RET1	B-GENE
+cells	O
+,	O
+using	O
+a	O
+variety	O
+of	O
+tRNA	O
+templates	O
+.	O
+
+Guiding	O
+patients	O
+in	O
+the	O
+decision	O
+should	O
+involve	O
+a	O
+multidisciplinary	O
+team	O
+composed	O
+of	O
+a	O
+surgical	O
+oncologist	O
+,	O
+geneticist	O
+,	O
+pathologist	O
+,	O
+psychotherapist	O
+and	O
+plastic	O
+surgeon	O
+.	O
+
+These	O
+factors	O
+belong	O
+to	O
+a	O
+set	O
+of	O
+genetically	O
+distinct	O
+molecules	O
+,	O
+including	O
+AP	B-GENE
+-	I-GENE
+4	I-GENE
+and	O
+MLTF	B-GENE
+,	O
+that	O
+bind	O
+to	O
+the	O
+CACCTGTC	O
+motif	O
+or	O
+related	O
+sequences	O
+.	O
+
+Among	O
+known	O
+flea	O
+larvae	O
+,	O
+the	O
+genus	O
+Anomiopsyllus	O
+(	O
+Anomiopsyllinae	O
+,	O
+Anomiopsyllini	O
+)	O
+is	O
+as	O
+distinctive	O
+in	O
+larval	O
+form	O
+as	O
+are	O
+the	O
+adults	O
+.	O
+
+Here	O
+,	O
+we	O
+have	O
+used	O
+specific	O
+antibody	O
+to	O
+identify	O
+and	O
+characterize	O
+the	O
+SSN6	B-GENE
+protein	I-GENE
+.	O
+
+These	O
+latter	O
+results	O
+showed	O
+that	O
+the	O
+ABFI	B-GENE
+protein	I-GENE
+,	O
+like	O
+the	O
+RAP1	B-GENE
+protein	I-GENE
+,	O
+bound	O
+sequences	O
+required	O
+for	O
+positive	O
+as	O
+well	O
+as	O
+negative	O
+regulation	O
+of	O
+gene	O
+expression	O
+.	O
+
+Clinical	O
+nutrition	O
+of	O
+adult	O
+horses	O
+.	O
+
+The	O
+computer	O
+-	O
+programmed	O
+cytocentrifuge	O
+is	O
+currently	O
+most	O
+popular	O
+.	O
+
+RNase	B-GENE
+protection	O
+assays	O
+reveal	O
+that	O
+this	O
+gene	O
+,	O
+unr	B-GENE
+,	O
+is	O
+transcribed	O
+in	O
+the	O
+same	O
+direction	O
+as	O
+N	B-GENE
+-	I-GENE
+ras	I-GENE
+and	O
+that	O
+its	O
+3	O
+'	O
+end	O
+is	O
+located	O
+just	O
+130	O
+base	O
+pairs	O
+away	O
+from	O
+the	O
+point	O
+at	O
+which	O
+N	B-GENE
+-	I-GENE
+ras	I-GENE
+transcription	O
+begins	O
+.	O
+
+Isolation	O
+of	O
+a	O
+temperature	O
+-	O
+sensitive	O
+mutant	O
+with	O
+an	O
+altered	O
+tRNA	B-GENE
+nucleotidyltransferase	I-GENE
+and	O
+cloning	O
+of	O
+the	O
+gene	B-GENE
+encoding	I-GENE
+tRNA	I-GENE
+nucleotidyltransferase	I-GENE
+in	I-GENE
+the	I-GENE
+yeast	I-GENE
+Saccharomyces	I-GENE
+cerevisiae	I-GENE
+.	O
+
+The	O
+juxtamembrane	O
+region	O
+of	O
+the	O
+insulin	B-GENE
+receptor	I-GENE
+(	I-GENE
+IR	I-GENE
+)	I-GENE
+beta	I-GENE
+-	I-GENE
+subunit	I-GENE
+contains	O
+an	O
+unphosphorylated	O
+tyrosyl	O
+residue	O
+(	O
+Tyr960	O
+)	O
+that	O
+is	O
+essential	O
+for	O
+insulin	B-GENE
+-	O
+stimulated	O
+tyrosyl	O
+phosphorylation	O
+of	O
+some	O
+endogenous	O
+substrates	O
+and	O
+certain	O
+biological	O
+responses	O
+(	O
+White	O
+,	O
+M	O
+.	O
+F	O
+.	O
+,	O
+Livingston	O
+,	O
+J	O
+.	O
+N	O
+.	O
+,	O
+Backer	O
+,	O
+J	O
+.	O
+M	O
+.	O
+,	O
+Lauris	O
+,	O
+V	O
+.	O
+,	O
+Dull	O
+,	O
+T	O
+.	O
+J	O
+.	O
+,	O
+Ullrich	O
+,	O
+A	O
+.	O
+,	O
+and	O
+Kahn	O
+,	O
+C	O
+.	O
+R	O
+.	O
+
+This	O
+gene	O
+joins	O
+the	O
+group	O
+of	O
+genes	O
+whose	O
+members	O
+are	O
+rapidly	O
+transcribed	O
+in	O
+response	O
+to	O
+insulin	B-GENE
+and	O
+other	O
+mitogens	O
+.	O
+
+The	O
+3	O
+'	O
+region	O
+,	O
+GA2	B-GENE
+,	O
+is	O
+necessary	O
+for	O
+maximal	O
+expression	O
+.	O
+
+Pups	O
+placed	O
+into	O
+the	O
+novel	O
+environment	O
+with	O
+their	O
+mothers	O
+exhibited	O
+an	O
+intermediate	O
+level	O
+of	O
+DA	O
+turnover	O
+.	O
+
+The	O
+efficacy	O
+and	O
+safety	O
+of	O
+a	O
+novel	O
+percutaneous	O
+anaesthetic	O
+preparation	O
+based	O
+on	O
+amethocaine	O
+has	O
+been	O
+investigated	O
+in	O
+the	O
+paediatric	O
+clinical	O
+environment	O
+.	O
+
+Homozygous	O
+protein	B-GENE
+C	I-GENE
+(	O
+PC	B-GENE
+)	O
+deficiency	O
+is	O
+reported	O
+in	O
+two	O
+siblings	O
+(	O
+girl	O
+and	O
+boy	O
+)	O
+who	O
+received	O
+their	O
+proper	O
+diagnoses	O
+at	O
+the	O
+ages	O
+of	O
+7	O
+4	O
+/	O
+12	O
+and	O
+1	O
+3	O
+/	O
+12	O
+years	O
+respectively	O
+.	O
+
+The	O
+grandfather	O
+and	O
+the	O
+granddaughter	O
+both	O
+had	O
+microtia	O
+and	O
+meatal	O
+atresia	O
+,	O
+whereas	O
+the	O
+daughter	O
+had	O
+a	O
+normal	O
+outer	O
+ear	O
+except	O
+for	O
+a	O
+narrow	O
+meatus	O
+and	O
+auricular	O
+appendages	O
+.	O
+
+Abnormal	O
+intrapulmonary	O
+shunting	O
+(	O
+IPS	O
+)	O
+,	O
+which	O
+was	O
+proved	O
+in	O
+4	O
+cases	O
+by	O
+whole	O
+-	O
+body	O
+radionuclide	O
+scanning	O
+with	O
+99mTc	O
+-	O
+MAA	O
+,	O
+is	O
+suggested	O
+as	O
+the	O
+major	O
+cause	O
+of	O
+cyanosis	O
+in	O
+liver	O
+cirrhosis	O
+.	O
+
+More	O
+generally	O
+,	O
+Ets1	B-GENE
+and	O
+Ets2	B-GENE
+could	O
+regulate	O
+transcription	O
+of	O
+cellular	O
+genes	O
+.	O
+
+Within	O
+this	O
+sequence	O
+the	O
+MSAS	B-GENE
+gene	I-GENE
+was	O
+identified	O
+as	O
+a	O
+5322	O
+-	O
+bp	O
+-	O
+long	O
+open	O
+reading	O
+frame	O
+coding	O
+for	O
+a	O
+protein	O
+of	O
+1774	O
+amino	O
+acids	O
+and	O
+190	O
+,	O
+731	O
+Da	O
+molecular	O
+mass	O
+.	O
+
+Horseradish	B-GENE
+peroxidase	I-GENE
+as	O
+a	O
+permeability	O
+marker	O
+in	O
+injured	O
+rat	O
+caudal	O
+and	O
+iliac	O
+arteries	O
+.	O
+
+Standardized	O
+gastric	O
+wall	O
+specimens	O
+from	O
+the	O
+area	O
+of	O
+grossly	O
+healed	O
+ulcers	O
+were	O
+obtained	O
+,	O
+processed	O
+,	O
+and	O
+evaluated	O
+by	O
+light	O
+microscopy	O
+and	O
+by	O
+transmission	O
+electron	O
+microscopy	O
+.	O
+
+2	O
+.	O
+
+The	O
+effects	O
+of	O
+coenzyme	O
+Q10	O
+(	O
+CoQ	O
+)	O
+and	O
+captopril	O
+on	O
+functional	O
+capacity	O
+,	O
+hemodynamics	O
+and	O
+survival	O
+were	O
+studied	O
+in	O
+154	O
+rats	O
+that	O
+recovered	O
+after	O
+experimental	O
+myocardial	O
+infarction	O
+.	O
+
+Evidence	O
+that	O
+therapeutic	O
+alterations	O
+of	O
+a	O
+circadian	O
+rhythm	O
+for	O
+gastric	O
+emptying	O
+response	O
+may	O
+be	O
+possible	O
+.	O
+
+The	O
+interrelation	O
+of	O
+the	O
+levels	O
+of	O
+glucocorticoids	O
+and	O
+insulin	B-GENE
+in	O
+the	O
+blood	O
+of	O
+irradiated	O
+animals	O
+
+This	O
+last	O
+includes	O
+tissue	O
+O2	O
+transfer	O
+(	O
+Ft	O
+'	O
+)	O
+and	O
+mitochondrial	O
+O2	O
+utilization	O
+(	O
+Fm	O
+'	O
+)	O
+.	O
+
+Foveating	O
+saccades	O
+,	O
+therefore	O
+,	O
+can	O
+be	O
+distinguished	O
+from	O
+other	O
+FEMs	O
+on	O
+the	O
+basis	O
+of	O
+speed	O
+.	O
+
+Incidence	O
+correlated	O
+with	O
+the	O
+grade	O
+of	O
+oral	O
+hygiene	O
+und	O
+periodontal	O
+disease	O
+.	O
+
+Our	O
+study	O
+shows	O
+that	O
+the	O
+area	O
+of	O
+Alcoy	O
+is	O
+a	O
+medium	O
+MS	O
+risk	O
+region	O
+according	O
+to	O
+the	O
+thesis	O
+of	O
+Kurzke	O
+,	O
+although	O
+high	O
+MS	O
+areas	O
+may	O
+be	O
+found	O
+,	O
+thus	O
+confirming	O
+that	O
+MS	O
+distribution	O
+in	O
+southern	O
+Europe	O
+is	O
+not	O
+uniform	O
+.	O
+
+On	O
+an	O
+antithrombin	B-GENE
+unit	O
+basis	O
+,	O
+CY	O
+216	O
+and	O
+CY	O
+222	O
+were	O
+equivalent	O
+and	O
+more	O
+potent	O
+than	O
+UH	O
+.	O
+
+Chick	B-GENE
+brain	I-GENE
+actin	I-GENE
+depolymerizing	I-GENE
+factor	I-GENE
+(	O
+ADF	B-GENE
+)	O
+is	O
+a	O
+19	O
+-	O
+kDa	O
+protein	O
+that	O
+severs	O
+actin	B-GENE
+filaments	I-GENE
+and	O
+binds	O
+actin	B-GENE
+monomers	I-GENE
+.	O
+
+Initial	O
+experience	O
+with	O
+a	O
+serotonin	O
+agonist	O
+.	O
+
+Comprehensive	O
+care	O
+of	O
+the	O
+patient	O
+exposed	O
+to	O
+a	O
+human	O
+teratogen	O
+may	O
+also	O
+include	O
+discussion	O
+of	O
+prenatal	O
+diagnostic	O
+procedures	O
+and	O
+other	O
+pregnancy	O
+management	O
+options	O
+.	O
+
+Primer	O
+extension	O
+analysis	O
+and	O
+RNA	O
+sequencing	O
+demonstrates	O
+that	O
+the	O
+transcription	O
+start	O
+point	O
+of	O
+rat	B-GENE
+ODC	I-GENE
+mRNA	I-GENE
+is	O
+located	O
+303	O
+nt	O
+upstream	O
+from	O
+the	O
+A	O
+residue	O
+in	O
+the	O
+start	O
+codon	O
+.	O
+
+For	O
+85Sr	O
+,	O
+larger	O
+-	O
+than	O
+-	O
+expected	O
+distribution	O
+coefficients	O
+were	O
+obtained	O
+in	O
+the	O
+desorption	O
+experiments	O
+,	O
+an	O
+indication	O
+of	O
+the	O
+irreversible	O
+formation	O
+of	O
+metal	O
+-	O
+oxyhydroxides	O
+during	O
+a	O
+slow	O
+reaction	O
+.	O
+
+Gene	O
+constructs	O
+possessing	O
+the	O
+complete	B-GENE
+tat	I-GENE
+,	O
+rev	B-GENE
+(	O
+tat	B-GENE
++	I-GENE
+rev	B-GENE
++	I-GENE
+)	O
+and	O
+env	B-GENE
+genes	I-GENE
+were	O
+transiently	O
+expressed	O
+in	O
+COS	O
+-	O
+1	O
+cells	O
+as	O
+precursor	B-GENE
+SU	I-GENE
+-	I-GENE
+TM	I-GENE
+(	O
+gp160	B-GENE
+)	O
+,	O
+SU	B-GENE
+.	I-GENE
+TM	I-GENE
+(	O
+gp120	B-GENE
+x	I-GENE
+41	I-GENE
+)	O
+,	O
+and	O
+nucleolar	B-GENE
+rev	I-GENE
+protein	I-GENE
+.	O
+
+This	O
+growth	O
+arrest	O
+is	O
+partly	O
+suppressed	O
+on	O
+minimal	O
+medium	O
+or	O
+under	O
+conditions	O
+in	O
+which	O
+the	O
+cells	O
+are	O
+less	O
+dependent	O
+on	O
+mitochondrial	O
+metabolism	O
+.	O
+
+Giant	O
+pilomatrix	O
+carcinoma	O
+:	O
+report	O
+and	O
+review	O
+of	O
+the	O
+literature	O
+.	O
+
+Further	O
+studies	O
+of	O
+mandibular	O
+movement	O
+at	O
+initial	O
+tooth	O
+contact	O
+.	O
+
+Each	O
+parent	O
+interacted	O
+with	O
+their	O
+4	O
+-	O
+or	O
+5	O
+-	O
+year	O
+-	O
+old	O
+son	O
+or	O
+daughter	O
+in	O
+each	O
+of	O
+two	O
+conversations	O
+-	O
+-	O
+unstructured	O
+(	O
+social	O
+conversation	O
+)	O
+and	O
+structured	O
+(	O
+task	O
+activity	O
+)	O
+.	O
+
+Droperidol	O
+-	O
+induced	O
+extrapyramidal	O
+symptoms	O
+in	O
+an	O
+adolescent	O
+following	O
+strabismus	O
+surgery	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+the	O
+cis	O
+-	O
+regulatory	O
+elements	O
+required	O
+for	O
+developmental	O
+control	O
+of	O
+the	O
+HaG3	B-GENE
+-	I-GENE
+A	I-GENE
+helianthinin	I-GENE
+gene	I-GENE
+are	O
+located	O
+in	O
+a	O
+2	O
+.	O
+4	O
+kb	O
+upstream	O
+region	O
+of	O
+this	O
+gene	O
+.	O
+
+The	O
+induction	O
+by	O
+pseudorabies	O
+virus	O
+of	O
+an	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+construct	I-GENE
+containing	O
+the	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+TATA	I-GENE
+box	I-GENE
+and	O
+the	O
+RNA	O
+start	O
+site	O
+(	O
+"	O
+initiator	O
+"	O
+or	O
+Inr	O
+element	O
+)	O
+but	O
+not	O
+the	O
+MRE	O
+region	O
+was	O
+also	O
+repressed	O
+by	O
+Dex	O
+in	O
+the	O
+presence	O
+of	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+GR	I-GENE
+.	O
+
+Some	O
+mutations	O
+affected	O
+Dhfr	B-GENE
+in	O
+a	O
+qualitative	O
+manner	O
+,	O
+such	O
+as	O
+by	O
+changing	O
+the	O
+startpoint	O
+of	O
+one	O
+of	O
+the	O
+major	O
+Dhfr	B-GENE
+transcripts	I-GENE
+or	O
+changing	O
+the	O
+relative	O
+abundance	O
+of	O
+the	O
+two	O
+major	O
+Dhfr	B-GENE
+transcripts	I-GENE
+.	O
+
+The	O
+glial	O
+cyst	O
+wall	O
+was	O
+lined	O
+in	O
+part	O
+by	O
+flattened	O
+or	O
+cuboidal	O
+epithelium	O
+.	O
+
+We	O
+conclude	O
+that	O
+class	O
+I	O
+cytologic	O
+smears	O
+with	O
+moderate	O
+to	O
+severe	O
+inflammation	O
+may	O
+be	O
+associated	O
+with	O
+findings	O
+of	O
+condylomata	O
+and	O
+cervical	O
+dysplasia	O
+.	O
+
+As	O
+in	O
+mammals	O
+,	O
+considerable	O
+nucleotide	O
+diversity	O
+was	O
+observed	O
+at	O
+the	O
+junctions	O
+of	O
+the	O
+variable	O
+,	O
+diversity	O
+,	O
+and	O
+joining	O
+elements	O
+in	O
+chicken	B-GENE
+TCR	I-GENE
+beta	I-GENE
+cDNAs	I-GENE
+.	O
+
+The	O
+protooncogene	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+encodes	O
+a	O
+nuclear	O
+transcription	O
+factor	O
+that	O
+binds	O
+to	O
+DNA	O
+in	O
+a	O
+sequence	O
+-	O
+specific	O
+manner	O
+and	O
+transactivates	O
+transcription	O
+of	O
+several	O
+viral	O
+and	O
+cellular	O
+genes	O
+.	O
+
+Modification	O
+by	O
+this	O
+latter	O
+compound	O
+was	O
+so	O
+extensive	O
+that	O
+the	O
+amount	O
+of	O
+membrane	O
+-	O
+associated	O
+N	O
+-	O
+myristoylated	O
+protein	O
+was	O
+decreased	O
+.	O
+
+S6	B-GENE
+kinase	I-GENE
+activation	O
+requires	O
+displacement	O
+of	O
+this	O
+inhibitory	O
+segment	O
+,	O
+which	O
+is	O
+proposed	O
+to	O
+occur	O
+consequent	O
+to	O
+its	O
+multiple	O
+phosphorylation	O
+.	O
+
+Cerebral	O
+flow	O
+and	O
+resistance	O
+showed	O
+minor	O
+reductions	O
+with	O
+HD	O
+.	O
+
+Utilization	O
+of	O
+alternative	O
+polyadenylation	O
+signals	O
+was	O
+previously	O
+shown	O
+to	O
+generate	O
+two	O
+sialophorin	B-GENE
+mRNAs	I-GENE
+of	I-GENE
+1	I-GENE
+.	I-GENE
+9	I-GENE
+and	I-GENE
+4	I-GENE
+.	I-GENE
+3	I-GENE
+kb	I-GENE
+,	O
+which	O
+differ	O
+in	O
+the	O
+length	O
+of	O
+their	O
+3	O
+'	O
+untranslated	O
+regions	O
+.	O
+
+Presidential	O
+address	O
+1990	O
+-	O
+-	O
+coming	O
+in	O
+from	O
+the	O
+cold	O
+.	O
+
+The	O
+Jenkins	O
+Activity	O
+Survey	O
+and	O
+the	O
+CPI	O
+-	O
+revised	O
+:	O
+further	O
+evidence	O
+of	O
+adaptive	O
+and	O
+maladaptive	O
+type	O
+A	O
+traits	O
+.	O
+
+There	O
+was	O
+evidence	O
+of	O
+attenuated	O
+regression	O
+slopes	O
+relating	O
+recalled	O
+to	O
+observed	O
+portion	O
+sizes	O
+for	O
+4	O
+of	O
+the	O
+10	O
+food	O
+groups	O
+;	O
+adjusted	O
+r2	O
+values	O
+for	O
+the	O
+recalled	O
+portion	O
+sizes	O
+ranged	O
+from	O
+0	O
+.	O
+02	O
+to	O
+0	O
+.	O
+94	O
+.	O
+
+The	O
+result	O
+suggests	O
+that	O
+this	O
+non	O
+-	O
+invasive	O
+TTD	O
+method	O
+is	O
+easily	O
+available	O
+and	O
+useful	O
+in	O
+monitoring	O
+the	O
+intraoperative	O
+cardiac	O
+output	O
+.	O
+
+The	O
+TUP1	B-GENE
+gene	I-GENE
+was	O
+isolated	O
+in	O
+a	O
+screen	O
+for	O
+genes	O
+that	O
+regulate	O
+mating	O
+type	O
+(	O
+V	O
+.	O
+L	O
+.	O
+
+The	O
+SUP44	B-GENE
+suppressor	I-GENE
+mutation	I-GENE
+occurs	O
+near	O
+a	O
+region	O
+of	O
+the	O
+protein	O
+that	O
+corresponds	O
+to	O
+the	O
+known	O
+positions	O
+of	O
+alterations	O
+in	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+S5	I-GENE
+ram	I-GENE
+mutations	I-GENE
+.	O
+
+Interestingly	O
+,	O
+disruption	O
+of	O
+the	O
+VPS34	B-GENE
+locus	I-GENE
+resulted	O
+in	O
+a	O
+temperature	O
+-	O
+sensitive	O
+growth	O
+defect	O
+,	O
+indicating	O
+that	O
+the	O
+VPS34	B-GENE
+gene	I-GENE
+is	O
+essential	O
+for	O
+vegetative	O
+growth	O
+only	O
+at	O
+elevated	O
+growth	O
+temperatures	O
+.	O
+
+We	O
+describe	O
+a	O
+case	O
+of	O
+a	O
+perinephric	O
+abscess	O
+treated	O
+with	O
+amphotericin	O
+B	O
+and	O
+nephrectomy	O
+.	O
+
+This	O
+interaction	O
+occurs	O
+over	O
+a	O
+wide	O
+range	O
+of	O
+both	O
+parameters	O
+;	O
+for	O
+charge	O
+density	O
+from	O
+at	O
+least	O
+10	O
+to	O
+800	O
+microC	O
+/	O
+cm2	O
+and	O
+,	O
+for	O
+charge	O
+per	O
+phase	O
+,	O
+from	O
+at	O
+least	O
+0	O
+.	O
+05	O
+to	O
+5	O
+.	O
+0	O
+microC	O
+per	O
+phase	O
+.	O
+
+Perceptions	O
+of	O
+illness	O
+intrusiveness	O
+were	O
+significantly	O
+higher	O
+when	O
+both	O
+muscle	O
+cramp	O
+and	O
+headache	O
+symptoms	O
+occurred	O
+during	O
+one	O
+or	O
+more	O
+assessment	O
+intervals	O
+as	O
+compared	O
+to	O
+when	O
+muscle	O
+cramps	O
+or	O
+headaches	O
+,	O
+only	O
+,	O
+occurred	O
+.	O
+
+Results	O
+have	O
+surprisingly	O
+revealed	O
+the	O
+presence	O
+of	O
+three	O
+U14	B-GENE
+snRNA	I-GENE
+-	I-GENE
+homologous	I-GENE
+regions	I-GENE
+positioned	O
+within	O
+introns	O
+5	O
+,	O
+6	O
+,	O
+and	O
+8	O
+of	O
+the	O
+mouse	O
+cognate	O
+hsc70	B-GENE
+heat	O
+shock	O
+gene	O
+.	O
+
+65	O
+-	O
+kilodalton	O
+protein	O
+phosphorylated	O
+by	O
+interleukin	B-GENE
+2	I-GENE
+stimulation	O
+bears	O
+two	O
+putative	O
+actin	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+and	O
+two	O
+calcium	O
+-	O
+binding	O
+sites	O
+.	O
+
+The	O
+highly	O
+restrained	O
+girls	O
+had	O
+a	O
+significantly	O
+higher	O
+EAT	O
+score	O
+than	O
+the	O
+low	O
+-	O
+restrained	O
+girls	O
+,	O
+and	O
+shared	O
+with	O
+their	O
+mothers	O
+a	O
+susceptibility	O
+to	O
+the	O
+disinhibitory	O
+effects	O
+of	O
+negative	O
+mood	O
+states	O
+on	O
+their	O
+eating	O
+behaviour	O
+.	O
+
+Sequence	O
+and	O
+genetic	O
+organization	O
+of	O
+a	O
+Zymomonas	O
+mobilis	O
+gene	O
+cluster	O
+that	O
+encodes	O
+several	O
+enzymes	O
+of	O
+glucose	O
+metabolism	O
+.	O
+
+For	O
+this	O
+,	O
+cDNAs	O
+containing	O
+the	O
+60K	O
+,	O
+87K	O
+,	O
+110K	O
+and	O
+170K	O
+protein	O
+coding	O
+sequences	O
+were	O
+each	O
+provided	O
+with	O
+an	O
+ATG	O
+start	O
+codon	O
+and	O
+the	O
+cDNA	O
+containing	O
+the	O
+60K	O
+coding	O
+sequence	O
+with	O
+a	O
+TAA	O
+stop	O
+codon	O
+immediately	O
+downstream	O
+of	O
+the	O
+coding	O
+sequence	O
+.	O
+
+Finally	O
+,	O
+a	O
+complementary	O
+footprinting	O
+analysis	O
+of	O
+the	O
+upstream	O
+region	O
+of	O
+the	O
+constitutively	O
+expressed	O
+HSC82	B-GENE
+gene	I-GENE
+reveals	O
+the	O
+presence	O
+of	O
+three	O
+discrete	O
+protein	O
+complexes	O
+.	O
+
+Pathophysiology	O
+of	O
+bone	O
+loss	O
+in	O
+castrated	O
+animals	O
+.	O
+
+Auditory	O
+-	O
+visual	O
+interaction	O
+in	O
+the	O
+generation	O
+of	O
+saccades	O
+in	O
+man	O
+.	O
+
+First	O
+,	O
+each	O
+lung	O
+was	O
+cut	O
+into	O
+slices	O
+,	O
+from	O
+which	O
+primary	O
+disectors	O
+were	O
+sampled	O
+systematically	O
+with	O
+a	O
+known	O
+sampling	O
+fraction	O
+.	O
+
+The	O
+upstream	O
+promoter	O
+is	O
+located	O
+within	O
+the	O
+coding	O
+sequence	O
+of	O
+a	O
+divergent	O
+gene	O
+expressing	O
+a	O
+protein	O
+of	O
+Mr	O
+39	O
+kDa	O
+of	O
+unknown	O
+function	O
+.	O
+
+Assuming	O
+O2	O
+consumption	O
+of	O
+the	O
+isolated	O
+skin	O
+to	O
+be	O
+same	O
+as	O
+in	O
+situ	O
+,	O
+calculations	O
+showed	O
+that	O
+when	O
+water	O
+PO2	O
+was	O
+high	O
+(	O
+150	O
+mm	O
+Hg	O
+)	O
+,	O
+about	O
+40	O
+%	O
+of	O
+total	O
+cutaneous	O
+O2	O
+uptake	O
+was	O
+consumed	O
+by	O
+the	O
+skin	O
+.	O
+
+MCh	O
+infusion	O
+caused	O
+a	O
+concentration	O
+-	O
+dependent	O
+increase	O
+in	O
+airway	O
+resistance	O
+at	O
+constant	O
+QBA	O
+.	O
+
+Plasma	O
+concentrations	O
+of	O
+atracurium	O
+and	O
+laudanosine	O
+were	O
+0	O
+.	O
+73	O
+-	O
+3	O
+.	O
+11	O
+micrograms	O
+ml	O
+-	O
+1	O
+and	O
+0	O
+.	O
+48	O
+-	O
+8	O
+.	O
+65	O
+micrograms	O
+ml	O
+-	O
+1	O
+,	O
+respectively	O
+;	O
+CSF	O
+concentration	O
+of	O
+laudanosine	O
+was	O
+70	O
+-	O
+440	O
+ng	O
+ml	O
+-	O
+1	O
+.	O
+
+Plasma	O
+Al	O
+was	O
+obtained	O
+during	O
+each	O
+baseline	O
+and	O
+drug	O
+course	O
+.	O
+
+The	O
+survival	O
+in	O
+the	O
+case	O
+of	O
+these	O
+patients	O
+was	O
+studied	O
+five	O
+years	O
+later	O
+.	O
+
+The	O
+occurrence	O
+,	O
+maintenance	O
+and	O
+possible	O
+involvement	O
+of	O
+these	O
+repeated	O
+sequences	O
+,	O
+capable	O
+of	O
+forming	O
+stable	O
+secondary	O
+structures	O
+,	O
+are	O
+discussed	O
+in	O
+relation	O
+to	O
+their	O
+location	O
+in	O
+the	O
+region	O
+of	O
+control	O
+signals	O
+.	O
+
+IST	B-GENE
+is	O
+not	O
+the	O
+RNA	O
+target	O
+(	O
+TAR	O
+)	O
+for	O
+Tat	B-GENE
+trans	O
+-	O
+activation	O
+;	O
+however	O
+,	O
+because	O
+it	O
+relies	O
+entirely	O
+on	O
+cellular	O
+factors	O
+for	O
+activity	O
+,	O
+IST	B-GENE
+may	O
+serve	O
+to	O
+provide	O
+abundant	O
+RNA	O
+targets	O
+for	O
+Tat	B-GENE
+trans	O
+-	O
+activation	O
+without	O
+a	O
+requirement	O
+for	O
+full	O
+-	O
+length	O
+viral	O
+mRNA	O
+expression	O
+.	O
+
+Genotoxic	O
+activity	O
+of	O
+a	O
+tobacco	O
+-	O
+specific	O
+nitrosamine	O
+.	O
+
+The	O
+endodontal	O
+treatment	O
+need	O
+has	O
+been	O
+forming	O
+a	O
+clinical	O
+order	O
+of	O
+magnitude	O
+.	O
+
+These	O
+results	O
+may	O
+suggest	O
+involvement	O
+of	O
+peripheral	O
+enkephalins	O
+in	O
+pain	O
+modulation	O
+in	O
+patients	O
+with	O
+episodic	O
+cluster	O
+headache	O
+.	O
+
+Effects	O
+of	O
+cisapride	O
+on	O
+upper	O
+-	O
+gastrointestinal	O
+motility	O
+and	O
+digestive	O
+hormones	O
+
+Common	O
+foot	O
+pathologies	O
+are	O
+heel	O
+pain	O
+,	O
+metatarsalgia	O
+,	O
+hammertoes	O
+and	O
+clawtoes	O
+,	O
+bunions	O
+,	O
+hallux	O
+rigidus	O
+,	O
+corns	O
+and	O
+calluses	O
+,	O
+nail	O
+pathologies	O
+,	O
+arthritis	O
+,	O
+and	O
+neuropathies	O
+.	O
+
+Liver	O
+dysfunction	O
+in	O
+the	O
+presence	O
+of	O
+different	O
+adverse	O
+reactions	O
+presented	O
+with	O
+a	O
+higher	O
+activity	O
+in	O
+the	O
+blood	O
+serum	O
+of	O
+indicator	O
+liver	O
+enzymes	O
+and	O
+its	O
+impaired	O
+protein	O
+-	O
+forming	O
+function	O
+.	O
+
+Coenzyme	O
+Q10	O
+:	O
+blood	O
+levels	O
+and	O
+metabolic	O
+demand	O
+.	O
+
+The	O
+CT	O
+characteristics	O
+are	O
+discussed	O
+and	O
+the	O
+recent	O
+literature	O
+is	O
+reviewed	O
+.	O
+
+Unfortunately	O
+,	O
+these	O
+preservatives	O
+may	O
+also	O
+interfere	O
+with	O
+microbiological	O
+assays	O
+used	O
+to	O
+determine	O
+product	O
+sterility	O
+or	O
+bioburden	O
+levels	O
+.	O
+
+In	O
+26	O
+patients	O
+with	O
+angina	O
+pectoris	O
+,	O
+the	O
+changes	O
+of	O
+LVEF	O
+,	O
+LVESV	O
+and	O
+PSP	O
+/	O
+LVESV	O
+were	O
+more	O
+sensitive	O
+for	O
+the	O
+detection	O
+of	O
+exercise	O
+-	O
+induced	O
+ischemia	O
+than	O
+the	O
+appearance	O
+of	O
+chest	O
+pain	O
+and	O
+the	O
+changes	O
+of	O
+ECG	O
+.	O
+
+In	O
+both	O
+groups	O
+there	O
+were	O
+5	O
+management	O
+failure	O
+of	O
+therapy	O
+,	O
+so	O
+that	O
+alternative	O
+medication	O
+or	O
+a	O
+cesarean	O
+section	O
+lead	O
+to	O
+delivery	O
+.	O
+
+Serum	O
+Fibrin	B-GENE
+Degradation	I-GENE
+Products	I-GENE
+(	O
+FDP	B-GENE
+)	O
+were	O
+determined	O
+in	O
+50	O
+oral	O
+cancer	O
+patients	O
+and	O
+50	O
+normal	O
+individuals	O
+prior	O
+to	O
+any	O
+kind	O
+of	O
+treatment	O
+.	O
+
+The	O
+uteroglobin	B-GENE
+promoter	I-GENE
+contains	O
+a	O
+noncanonical	O
+estrogen	O
+responsive	O
+element	O
+.	O
+
+Prostaglandin	O
+synthesis	O
+inhibitors	O
+have	O
+been	O
+shown	O
+to	O
+delay	O
+healing	O
+of	O
+bone	O
+and	O
+this	O
+has	O
+led	O
+to	O
+limitations	O
+on	O
+their	O
+use	O
+clinically	O
+in	O
+some	O
+situations	O
+.	O
+
+The	O
+inspiratory	O
+oxygen	O
+concentration	O
+needed	O
+(	O
+FiO2	O
+)	O
+and	O
+the	O
+Horowitz	O
+quotient	O
+differed	O
+in	O
+a	O
+highly	O
+significant	O
+manner	O
+beginning	O
+on	O
+the	O
+1st	O
+day	O
+after	O
+trauma	O
+.	O
+
+The	O
+corn	O
+and	O
+mineral	O
+oil	O
+emulsions	O
+were	O
+almost	O
+as	O
+effective	O
+as	O
+milk	O
+but	O
+less	O
+effective	O
+than	O
+sucrose	O
+(	O
+0	O
+.	O
+3M	O
+)	O
+in	O
+stimulating	O
+ingestion	O
+.	O
+
+Significance	O
+of	O
+thin	O
+glomerular	O
+basement	O
+membranes	O
+in	O
+hematuric	O
+children	O
+.	O
+
+Significance	O
+of	O
+cytokine	O
+production	O
+and	O
+adhesion	O
+molecules	O
+in	O
+malarial	O
+immunopathology	O
+.	O
+
+The	O
+former	O
+procedure	O
+is	O
+economical	O
+but	O
+complicated	O
+,	O
+whereas	O
+the	O
+latter	O
+is	O
+simple	O
+and	O
+labour	O
+-	O
+saving	O
+,	O
+but	O
+a	O
+special	O
+ultrafiltration	O
+tube	O
+is	O
+required	O
+.	O
+
+Simple	O
+method	O
+for	O
+determination	O
+of	O
+the	O
+cephalosporin	O
+DQ	O
+-	O
+2556	O
+in	O
+biological	O
+fluids	O
+by	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatography	O
+.	O
+
+Since	O
+one	O
+group	O
+of	O
+adolescents	O
+more	O
+difficult	O
+to	O
+influence	O
+are	O
+those	O
+whose	O
+parents	O
+smoke	O
+,	O
+parental	O
+involvement	O
+in	O
+smoking	O
+prevention	O
+may	O
+be	O
+a	O
+powerful	O
+enhancer	O
+.	O
+
+Further	O
+research	O
+is	O
+recommended	O
+to	O
+identify	O
+the	O
+coping	O
+styles	O
+associated	O
+with	O
+the	O
+high	O
+EE	O
+/	O
+low	O
+EE	O
+research	O
+classification	O
+.	O
+
+Staining	O
+with	O
+IF	O
+MoAB	O
+alone	O
+of	O
+BAL	O
+fluid	O
+only	O
+seemed	O
+to	O
+be	O
+even	O
+more	O
+sensitive	O
+than	O
+silver	O
+methenamine	O
+staining	O
+of	O
+BAL	O
+,	O
+TBB	O
+and	O
+brushing	O
+material	O
+.	O
+
+Ultrastructural	O
+and	O
+morphometric	O
+study	O
+of	O
+the	O
+myeloid	O
+parenchyma	O
+cells	O
+of	O
+mice	O
+prior	O
+and	O
+after	O
+X	O
+-	O
+ray	O
+exposure	O
+
+Using	O
+an	O
+audiotape	O
+cassette	O
+and	O
+headphones	O
+the	O
+duration	O
+of	O
+the	O
+hallucinations	O
+decreased	O
+significantly	O
+.	O
+
+The	O
+mean	O
+change	O
+in	O
+HbA1	B-GENE
+,	O
+adjusted	O
+for	O
+the	O
+initial	O
+value	O
+,	O
+was	O
+-	O
+0	O
+.	O
+4	O
+%	O
+in	O
+the	O
+experimental	O
+and	O
++	O
+0	O
+.	O
+5	O
+%	O
+in	O
+the	O
+control	O
+group	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Effect	O
+of	O
+biliary	O
+obstruction	O
+and	O
+cholangitis	O
+on	O
+serum	B-GENE
+SPan	I-GENE
+-	I-GENE
+1	I-GENE
+level	O
+
+Very	O
+good	O
+accuracy	O
+(	O
+r	O
+greater	O
+than	O
+0	O
+.	O
+9	O
+)	O
+was	O
+found	O
+when	O
+except	O
+comparing	O
+H	O
+*	O
+2	O
+with	O
+the	O
+other	O
+machine	O
+and	O
+the	O
+reference	O
+methods	O
+,	O
+except	O
+for	O
+MCHCH	O
+and	O
+basophil	O
+count	O
+.	O
+
+The	O
+second	O
+part	O
+of	O
+this	O
+paper	O
+shows	O
+some	O
+medical	O
+applications	O
+of	O
+these	O
+two	O
+aspects	O
+of	O
+NMR	O
+,	O
+with	O
+help	O
+of	O
+some	O
+examples	O
+,	O
+taken	O
+from	O
+the	O
+literature	O
+,	O
+according	O
+to	O
+what	O
+is	O
+concerned	O
+with	O
+endocrinology	O
+.	O
+
+Interlimb	O
+coordination	O
+during	O
+fictive	O
+locomotion	O
+in	O
+the	O
+thalamic	O
+cat	O
+.	O
+
+Antileukoproteinase	B-GENE
+(	O
+ALP	B-GENE
+)	O
+is	O
+a	O
+low	O
+mol	O
+wt	O
+mucosal	O
+secretory	O
+protein	O
+which	O
+,	O
+in	O
+human	O
+tissues	O
+,	O
+inhibits	O
+the	O
+activities	O
+of	O
+the	O
+neutral	O
+serine	B-GENE
+lysosomal	I-GENE
+proteinases	I-GENE
+elastase	B-GENE
+and	O
+cathepsin	B-GENE
+-	I-GENE
+G	I-GENE
+.	O
+
+By	O
+introducing	O
+a	O
+series	O
+of	O
+deletions	O
+in	O
+the	O
+vimentin	B-GENE
+promoter	O
+,	O
+we	O
+further	O
+restrict	O
+these	O
+sequences	O
+to	O
+30	O
+base	O
+pairs	O
+,	O
+located	O
+between	O
+241	O
+and	O
+210	O
+base	O
+pairs	O
+upstream	O
+of	O
+the	O
+mRNA	O
+cap	O
+site	O
+.	O
+
+In	O
+particular	O
+,	O
+71	O
+and	O
+69	O
+%	O
+amino	O
+acid	O
+sequence	O
+similarities	O
+were	O
+identified	O
+with	O
+hsp70	B-GENE
+of	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+and	I-GENE
+Bacillus	I-GENE
+megaterium	I-GENE
+,	O
+respectively	O
+.	O
+
+All	O
+89	O
+participating	O
+household	O
+members	O
+were	O
+anti	B-GENE
+-	I-GENE
+HIV	I-GENE
+seronegative	O
+,	O
+and	O
+78	O
+who	O
+were	O
+tested	O
+were	O
+serum	B-GENE
+p24	I-GENE
+antigen	I-GENE
+negative	O
+.	O
+
+To	O
+those	O
+of	O
+us	O
+who	O
+are	O
+not	O
+satisfied	O
+with	O
+the	O
+present	O
+outlook	O
+there	O
+is	O
+much	O
+to	O
+be	O
+investigated	O
+and	O
+much	O
+to	O
+be	O
+contributed	O
+.	O
+
+To	O
+determine	O
+the	O
+effects	O
+on	O
+the	O
+pulmonary	O
+barrier	O
+of	O
+several	O
+surface	O
+active	O
+agents	O
+,	O
+a	O
+series	O
+of	O
+metered	O
+dose	O
+inhalers	O
+(	O
+MDIs	O
+)	O
+was	O
+prepared	O
+and	O
+used	O
+to	O
+dose	O
+aerosolized	O
+surfactant	O
+to	O
+the	O
+airways	O
+of	O
+isolated	O
+perfused	O
+rat	O
+lungs	O
+.	O
+
+The	O
+beta	O
+chain	O
+contains	O
+five	O
+potential	O
+N	O
+-	O
+linked	O
+glycosylation	O
+sites	O
+,	O
+and	O
+endoglycosidase	B-GENE
+digestion	O
+suggested	O
+that	O
+the	O
+beta	O
+chain	O
+contained	O
+multiple	O
+complex	O
+carbohydrate	O
+side	O
+chains	O
+.	O
+
+The	O
+therapeutic	O
+protocole	O
+used	O
+at	O
+the	O
+Gustave	O
+Roussy	O
+Institute	O
+for	O
+invasive	O
+epithelioma	O
+of	O
+the	O
+uterine	O
+cervix	O
+rests	O
+,	O
+for	O
+limited	O
+forms	O
+(	O
+T1B	O
+-	O
+T2	O
+proximal	O
+)	O
+,	O
+on	O
+combined	O
+radiology	O
+and	O
+surgery	O
+.	O
+
+Thyrotropin	B-GENE
+-	O
+induced	O
+expression	O
+of	O
+a	O
+gene	O
+for	O
+a	O
+ribosomal	B-GENE
+protein	I-GENE
+related	O
+to	O
+the	O
+trk	B-GENE
+oncogene	I-GENE
+.	O
+
+The	O
+introns	O
+are	O
+1	O
+.	O
+6	O
+-	O
+1	O
+.	O
+9	O
+kbp	O
+long	O
+.	O
+
+After	O
+an	O
+initial	O
+titration	O
+period	O
+and	O
+adjustment	O
+of	O
+the	O
+therapeutic	O
+dose	O
+,	O
+the	O
+individual	O
+doses	O
+were	O
+from	O
+21	O
+to	O
+500	O
+micrograms	O
+/	O
+24	O
+hrs	O
+(	O
+mean	O
+160	O
+micrograms	O
+/	O
+24	O
+hrs	O
+)	O
+.	O
+
+In	O
+the	O
+first	O
+series	O
+of	O
+experiments	O
+,	O
+Sprague	O
+-	O
+Dawley	O
+male	O
+rats	O
+were	O
+implanted	O
+unilaterally	O
+with	O
+guide	O
+cannulas	O
+aimed	O
+at	O
+the	O
+lateral	O
+ventricle	O
+.	O
+
+Use	O
+of	O
+Selenastrum	O
+capricornutum	O
+and	O
+Microfeast	O
+as	O
+food	O
+for	O
+Daphnia	O
+pulex	O
+.	O
+
+The	O
+persistence	O
+of	O
+members	O
+of	O
+the	O
+prostigmatid	O
+families	O
+Tydeidae	O
+,	O
+Nanorchestidae	O
+and	O
+Tarsonemidae	O
+in	O
+the	O
+moisture	O
+-	O
+deficient	O
+90	O
+%	O
+-	O
+concentration	O
+treatments	O
+supports	O
+previous	O
+evidence	O
+of	O
+adaptations	O
+to	O
+low	O
+-	O
+water	O
+-	O
+content	O
+habitats	O
+.	O
+
+To	O
+define	O
+the	O
+mechanism	O
+responsible	O
+for	O
+the	O
+loss	O
+of	O
+transcription	O
+elongation	O
+blockage	O
+and	O
+resulting	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+deregulation	O
+in	O
+Burkitt	O
+'	O
+s	O
+lymphoma	O
+,	O
+we	O
+analyzed	O
+transcription	O
+patterns	O
+after	O
+transfer	O
+of	O
+normal	O
+and	O
+Burkitt	O
+'	O
+s	O
+lymphoma	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+alleles	O
+into	O
+murine	O
+cells	O
+and	O
+Xenopus	O
+oocyte	O
+germinal	O
+vesicles	O
+.	O
+
+From	O
+an	O
+RNK	O
+-	O
+16	O
+lambda	O
+-	O
+gt11	O
+library	O
+,	O
+we	O
+have	O
+isolated	O
+and	O
+sequenced	O
+a	O
+novel	O
+cDNA	O
+rat	B-GENE
+NK	I-GENE
+cell	I-GENE
+protease	I-GENE
+1	I-GENE
+(	O
+RNKP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+that	O
+has	O
+characteristics	O
+unique	O
+to	O
+serine	B-GENE
+proteases	I-GENE
+.	O
+
+The	O
+induction	O
+of	O
+RNKP	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+in	O
+the	O
+Con	B-GENE
+A	I-GENE
+-	O
+cultured	O
+spleen	O
+cells	O
+is	O
+accompanied	O
+by	O
+increases	O
+in	O
+both	O
+NK	O
+and	O
+lymphokine	O
+-	O
+activated	O
+killer	O
+lymphocyte	O
+activities	O
+.	O
+
+The	O
+paper	O
+is	O
+concerned	O
+with	O
+the	O
+data	O
+on	O
+change	O
+in	O
+the	O
+blood	O
+level	O
+of	O
+ACTH	B-GENE
+,	O
+STH	B-GENE
+,	O
+TSH	B-GENE
+,	O
+cortisol	O
+,	O
+T3	O
+,	O
+insulin	B-GENE
+,	O
+C	B-GENE
+-	I-GENE
+peptide	I-GENE
+during	O
+a	O
+25	O
+-	O
+minute	O
+session	O
+of	O
+respiration	O
+using	O
+a	O
+gaseous	O
+hypoxic	O
+mixture	O
+with	O
+10	O
+%	O
+oxygen	O
+(	O
+GHM	O
+-	O
+10	O
+)	O
+.	O
+
+The	O
+abscess	O
+was	O
+debrided	O
+and	O
+the	O
+septum	O
+was	O
+patched	O
+with	O
+a	O
+single	O
+layer	O
+of	O
+autologous	O
+pericardium	O
+.	O
+
+In	O
+18	O
+%	O
+lymphography	O
+was	O
+clearly	O
+positive	O
+and	O
+CT	O
+negative	O
+.	O
+
+The	O
+present	O
+study	O
+examined	O
+the	O
+effect	O
+of	O
+intensity	O
+,	O
+rate	O
+,	O
+and	O
+polarity	O
+on	O
+the	O
+spectral	O
+content	O
+of	O
+ABRs	O
+of	O
+15	O
+normal	O
+-	O
+hearing	O
+subjects	O
+.	O
+
+Similar	O
+memory	O
+impairments	O
+found	O
+in	O
+medial	O
+septal	O
+-	O
+vertical	O
+diagonal	O
+band	O
+of	O
+Broca	O
+and	O
+nucleus	O
+basalis	O
+lesioned	O
+rats	O
+:	O
+are	O
+memory	O
+defects	O
+induced	O
+by	O
+nucleus	O
+basalis	O
+lesions	O
+related	O
+to	O
+the	O
+degree	O
+of	O
+non	O
+-	O
+specific	O
+subcortical	O
+cell	O
+loss	O
+?	O
+The	O
+function	O
+of	O
+nucleus	O
+basalis	O
+(	O
+NB	O
+)	O
+and	O
+medial	O
+septal	O
+-	O
+vertical	O
+diagonal	O
+band	O
+of	O
+Broca	O
+(	O
+MS	O
+-	O
+VDBB	O
+)	O
+in	O
+a	O
+place	O
+navigation	O
+task	O
+requiring	O
+reference	O
+memory	O
+was	O
+investigated	O
+.	O
+
+Studies	O
+also	O
+have	O
+alluded	O
+to	O
+a	O
+relationship	O
+between	O
+the	O
+MSMR	O
+cyst	O
+and	O
+certain	O
+signs	O
+or	O
+symptoms	O
+of	O
+disease	O
+.	O
+
+The	O
+BAL	O
+-	O
+to	O
+-	O
+plasma	O
+specific	O
+activity	O
+of	O
+urea	O
+was	O
+about	O
+twice	O
+that	O
+of	O
+Na	O
++	O
+,	O
+indicating	O
+that	O
+urea	O
+diffused	O
+into	O
+the	O
+ELF	O
+more	O
+rapidly	O
+than	O
+Na	O
++	O
+during	O
+the	O
+70	O
+s	O
+that	O
+elapsed	O
+between	O
+the	O
+time	O
+the	O
+radioactive	O
+urea	O
+and	O
+Na	O
++	O
+were	O
+injected	O
+into	O
+the	O
+circulation	O
+and	O
+the	O
+time	O
+when	O
+lavage	O
+was	O
+complete	O
+.	O
+
+The	O
+kappa	O
+coefficient	O
+of	O
+agreement	O
+between	O
+the	O
+Patho	O
+Dx	O
+Kit	O
+and	O
+the	O
+standard	O
+method	O
+was	O
+0	O
+.	O
+958	O
+.	O
+
+Senior	O
+systems	O
+-	O
+-	O
+45	O
+;	O
+Mental	O
+health	O
+and	O
+illness	O
+in	O
+old	O
+age	O
+-	O
+-	O
+3	O
+.	O
+
+When	O
+normalized	O
+for	O
+imaging	O
+time	O
+,	O
+all	O
+parameters	O
+are	O
+significantly	O
+higher	O
+with	O
+RASE	O
+,	O
+with	O
+a	O
+C	O
+/	O
+A	O
+per	O
+unit	O
+time	O
+that	O
+was	O
+338	O
+%	O
+higher	O
+.	O
+
+Patients	O
+with	O
+acute	O
+myocardial	O
+infarction	O
+had	O
+higher	O
+plasma	O
+concentrations	O
+of	O
+neutrophil	B-GENE
+elastase	I-GENE
+and	O
+the	O
+non	O
+-	O
+peroxide	O
+diene	O
+conjugated	O
+isomer	O
+of	O
+linoleic	O
+acid	O
+than	O
+normal	O
+volunteers	O
+or	O
+patients	O
+with	O
+stable	O
+ischaemic	O
+heart	O
+disease	O
+.	O
+
+The	O
+cis	O
+-	O
+acting	O
+element	O
+,	O
+identified	O
+as	O
+CACGTGACCCG	O
+,	O
+is	O
+located	O
+34	O
+bp	O
+upstream	O
+from	O
+the	O
+transcription	O
+initiation	O
+site	O
+,	O
+and	O
+contains	O
+the	O
+core	O
+sequence	O
+of	O
+the	O
+upstream	O
+promoter	O
+sequence	O
+of	O
+Ad2MLP	B-GENE
+.	O
+
+The	O
+clinical	O
+relevance	O
+of	O
+these	O
+findings	O
+is	O
+strengthened	O
+by	O
+the	O
+observation	O
+that	O
+similar	O
+results	O
+were	O
+obtained	O
+when	O
+P	O
+.	O
+HCl	O
+was	O
+given	O
+by	O
+the	O
+intravenous	O
+route	O
+.	O
+
+TMBr	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+identical	O
+to	O
+striated	B-GENE
+muscle	I-GENE
+alpha	I-GENE
+-	I-GENE
+tropomyosin	I-GENE
+from	O
+amino	O
+acids	O
+1	O
+through	O
+258	O
+but	O
+contains	O
+a	O
+novel	O
+COOH	O
+-	O
+terminal	O
+region	O
+from	O
+amino	O
+acids	O
+259	O
+through	O
+281	O
+.	O
+
+The	O
+procedure	O
+has	O
+been	O
+applied	O
+to	O
+three	O
+materials	O
+:	O
+particle	O
+board	O
+with	O
+carpet	O
+;	O
+gypsum	O
+board	O
+with	O
+wallpaper	O
+;	O
+and	O
+plywood	O
+with	O
+polyurethane	O
+lacquer	O
+,	O
+for	O
+which	O
+the	O
+steady	O
+-	O
+state	O
+emission	O
+factors	O
+(	O
+mg	O
+m	O
+-	O
+2	O
+h	O
+-	O
+1	O
+)	O
+of	O
+several	O
+compounds	O
+are	O
+given	O
+.	O
+
+Intron	O
+1	O
+is	O
+6	O
+.	O
+5	O
+kb	O
+long	O
+,	O
+and	O
+the	O
+minimal	O
+sizes	O
+of	O
+introns	O
+2	O
+and	O
+3	O
+are	O
+estimated	O
+to	O
+be	O
+32	O
+kb	O
+each	O
+.	O
+
+After	O
+4	O
+h	O
+,	O
+lesions	O
+in	O
+the	O
+secretory	O
+part	O
+of	O
+the	O
+stomach	O
+were	O
+scored	O
+and	O
+mucosal	O
+prostaglandin	O
+E2	O
+synthesis	O
+was	O
+determined	O
+by	O
+the	O
+ex	O
+vivo	O
+prostaglandin	O
+generation	O
+technique	O
+.	O
+
+Comparison	O
+of	O
+transmembrane	O
+and	O
+cytoplasmic	O
+domains	O
+to	O
+a	O
+third	O
+cell	O
+-	O
+surface	O
+proteoglycan	O
+,	O
+48K5	B-GENE
+from	O
+human	O
+lung	O
+fibroblasts	O
+(	O
+Marynen	O
+,	O
+P	O
+.	O
+,	O
+Zhang	O
+,	O
+J	O
+.	O
+,	O
+Cassiman	O
+,	O
+J	O
+.	O
+,	O
+Vanden	O
+Berghe	O
+,	O
+H	O
+.	O
+,	O
+and	O
+David	O
+,	O
+C	O
+.	O
+
+Approximately	O
+65	O
+%	O
+of	O
+the	O
+total	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+phosphotransferase	I-GENE
+activity	O
+is	O
+recovered	O
+in	O
+particulate	O
+fractions	O
+of	O
+homogenates	O
+prepared	O
+from	O
+asynchronous	O
+populations	O
+of	O
+C	O
+.	O
+elegans	O
+.	O
+
+High	O
+levels	O
+of	O
+C	B-GENE
+subunits	I-GENE
+are	O
+observed	O
+in	O
+several	O
+subsequent	O
+larval	O
+and	O
+adult	O
+stages	O
+of	O
+development	O
+.	O
+
+A	O
+second	O
+,	O
+novel	O
+C	O
+subunit	O
+(	O
+CeCAT	B-GENE
+alpha	I-GENE
+'	I-GENE
+,	O
+374	O
+residues	O
+)	O
+has	O
+a	O
+unique	O
+56	O
+-	O
+residue	O
+carboxyl	O
+-	O
+terminal	O
+region	O
+that	O
+is	O
+generated	O
+by	O
+the	O
+alternative	O
+splicing	O
+of	O
+the	O
+C	B-GENE
+pre	I-GENE
+-	I-GENE
+mRNA	I-GENE
+.	O
+
+The	O
+alternative	O
+exon	O
+introduces	O
+the	O
+novel	O
+carboxyl	O
+terminus	O
+and	O
+a	O
+new	O
+translation	O
+stop	O
+signal	O
+,	O
+while	O
+simultaneously	O
+converting	O
+the	O
+coding	O
+sequence	O
+for	O
+40	O
+carboxyl	O
+-	O
+terminal	O
+residues	O
+in	O
+CeCAT	B-GENE
+alpha	I-GENE
+into	O
+3	O
+'	O
+-	O
+untranslated	O
+nucleotides	O
+.	O
+
+French	O
+,	O
+M	O
+.	O
+
+Slowly	O
+adapting	O
+type	O
+I	O
+mechanoreceptor	O
+discharge	O
+as	O
+a	O
+function	O
+of	O
+dynamic	O
+force	O
+versus	O
+dynamic	O
+displacement	O
+of	O
+glabrous	O
+skin	O
+of	O
+raccoon	O
+and	O
+squirrel	O
+monkey	O
+hand	O
+.	O
+
+Plasma	O
+lecithin	B-GENE
+/	I-GENE
+cholesterol	I-GENE
+acyltransferase	I-GENE
+(	O
+LCAT	B-GENE
+)	O
+activity	O
+in	O
+multiple	O
+-	O
+organ	O
+donors	O
+:	O
+a	O
+predictor	O
+of	O
+allograft	O
+viability	O
+in	O
+clinical	O
+liver	O
+transplantation	O
+.	O
+
+Axillary	O
+nodal	O
+status	O
+,	O
+tumour	O
+progesterone	B-GENE
+receptor	I-GENE
+status	O
+,	O
+and	O
+season	O
+of	O
+tumour	O
+detection	O
+significantly	O
+influenced	O
+survival	O
+in	O
+both	O
+older	O
+(	O
+greater	O
+than	O
+50	O
+yrs	O
+)	O
+and	O
+younger	O
+(	O
+less	O
+than	O
+50	O
+yrs	O
+)	O
+patients	O
+.	O
+
+The	O
+application	O
+of	O
+these	O
+microelectrodes	O
+to	O
+the	O
+measurement	O
+of	O
+rapid	O
+,	O
+transient	O
+changes	O
+in	O
+retinal	O
+[	O
+K	O
++	O
+]	O
+o	O
+is	O
+presented	O
+.	O
+
+Expression	O
+,	O
+cellular	O
+localization	O
+and	O
+in	O
+vitro	O
+transcription	O
+studies	O
+establish	O
+that	O
+cloned	B-GENE
+hUBF	I-GENE
+encodes	O
+a	O
+nucleolar	O
+factor	O
+that	O
+binds	O
+specifically	O
+to	O
+the	O
+upstream	O
+control	O
+element	O
+and	O
+core	O
+of	O
+the	O
+rRNA	O
+gene	O
+promoter	O
+to	O
+activate	O
+transcription	O
+in	O
+a	O
+binding	O
+site	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Combining	O
+multiple	O
+laboratory	O
+studies	O
+may	O
+be	O
+of	O
+value	O
+in	O
+predetermining	O
+the	O
+eventual	O
+outcome	O
+in	O
+near	O
+-	O
+drowning	O
+.	O
+
+There	O
+was	O
+a	O
+gradual	O
+increase	O
+in	O
+the	O
+myocyte	O
+diameter	O
+according	O
+to	O
+age	O
+in	O
+the	O
+biopsy	O
+and	O
+autopsy	O
+specimens	O
+.	O
+
+Despite	O
+the	O
+absence	O
+of	O
+exercise	O
+-	O
+induced	O
+asthma	O
+(	O
+EIA	O
+)	O
+while	O
+breathing	O
+WH	O
+air	O
+,	O
+asthmatic	O
+patients	O
+still	O
+had	O
+significantly	O
+higher	O
+mean	O
+GH	O
+increments	O
+than	O
+normal	O
+subjects	O
+(	O
+9	O
+.	O
+2	O
+vs	O
+2	O
+.	O
+3	O
+ng	O
+/	O
+ml	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+afferents	O
+'	O
+phase	O
+of	O
+response	O
+was	O
+unmodified	O
+by	O
+electrical	O
+EVS	O
+stimulation	O
+.	O
+
+Solving	O
+an	O
+age	O
+old	O
+problem	O
+.	O
+
+The	O
+distribution	O
+of	O
+their	O
+fibrinogen	B-GENE
+levels	O
+was	O
+Gaussian	O
+,	O
+but	O
+more	O
+wide	O
+-	O
+based	O
+than	O
+the	O
+distribution	O
+of	O
+our	O
+normal	O
+controls	O
+.	O
+
+In	O
+a	O
+stepwise	O
+logistic	O
+regression	O
+analysis	O
+of	O
+SPT	O
+and	O
+RAST	O
+data	O
+,	O
+the	O
+occurrence	O
+of	O
+serum	B-GENE
+IgE	I-GENE
+antibodies	I-GENE
+to	I-GENE
+P	I-GENE
+.	I-GENE
+orbiculare	I-GENE
+had	O
+the	O
+highest	O
+explanatory	O
+value	O
+for	O
+current	O
+eczema	O
+.	O
+
+The	O
+examination	O
+was	O
+focused	O
+on	O
+assessment	O
+of	O
+different	O
+types	O
+of	O
+drusen	O
+,	O
+on	O
+evaluation	O
+of	O
+the	O
+development	O
+and	O
+incidence	O
+of	O
+risk	O
+factors	O
+leading	O
+to	O
+complications	O
+and	O
+loss	O
+of	O
+central	O
+vision	O
+.	O
+
+They	O
+were	O
+then	O
+subjected	O
+to	O
+whole	O
+-	O
+body	O
+heat	O
+stress	O
+(	O
+water	O
+-	O
+perfused	O
+suits	O
+)	O
+,	O
+and	O
+the	O
+3	O
+minutes	O
+of	O
+LBNP	O
+was	O
+repeated	O
+.	O
+
+An	O
+NF1	B-GENE
+-	I-GENE
+related	I-GENE
+vitellogenin	I-GENE
+activator	I-GENE
+element	I-GENE
+mediates	O
+transcription	O
+from	O
+the	O
+estrogen	O
+-	O
+regulated	O
+Xenopus	B-GENE
+laevis	I-GENE
+vitellogenin	I-GENE
+promoter	I-GENE
+.	O
+
+At	O
+the	O
+carboxyl	O
+terminus	O
+,	O
+deletion	O
+as	O
+far	O
+as	O
+residue	O
+388	O
+did	O
+not	O
+affect	O
+in	O
+vitro	O
+TRF	B-GENE
+.	I-GENE
+C	I-GENE
+assembly	O
+,	O
+although	O
+trans	O
+-	O
+activating	O
+activity	O
+was	O
+abolished	O
+.	O
+
+The	O
+effects	O
+of	O
+mean	O
+luminance	O
+were	O
+also	O
+measured	O
+and	O
+a	O
+general	O
+expression	O
+that	O
+would	O
+take	O
+them	O
+into	O
+account	O
+was	O
+derived	O
+.	O
+
+Effect	O
+of	O
+hyperglycemia	O
+on	O
+pain	O
+threshold	O
+in	O
+alloxan	O
+-	O
+diabetic	O
+rats	O
+.	O
+
+We	O
+have	O
+synthesized	O
+[	O
+7	O
+,	O
+7	O
+-	O
+2H2	O
+]	O
+-	O
+19	O
+-	O
+OHA	O
+with	O
+high	O
+deuterium	O
+content	O
+and	O
+,	O
+together	O
+with	O
+[	O
+7	O
+,	O
+7	O
+-	O
+2H2	O
+]	O
+A	O
+and	O
+[	O
+9	O
+,	O
+11	O
+-	O
+2H2	O
+]	O
+estrone	O
+(	O
+E1	O
+)	O
+,	O
+have	O
+developed	O
+a	O
+quantitative	O
+assay	O
+of	O
+serum	O
+level	O
+19	O
+-	O
+OHA	O
+,	O
+A	O
+,	O
+and	O
+E1	O
+using	O
+the	O
+gas	O
+chromatography	O
+/	O
+mass	O
+spectrometry	O
+-	O
+mass	O
+fragmentography	O
+method	O
+to	O
+monitor	O
+individual	O
+subjects	O
+throughout	O
+pregnancy	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+these	O
+genes	O
+and	O
+their	O
+surrounding	O
+sequences	O
+are	O
+presented	O
+and	O
+compared	O
+with	O
+other	O
+known	O
+tRNA	O
+genes	O
+from	O
+plant	O
+mitochondria	O
+.	O
+
+Experiments	O
+were	O
+performed	O
+in	O
+which	O
+brain	O
+-	O
+stem	O
+auditory	O
+-	O
+evoked	O
+responses	O
+(	O
+BAERs	O
+)	O
+were	O
+elicited	O
+by	O
+two	O
+types	O
+of	O
+pseudorandom	O
+pulse	O
+trains	O
+:	O
+maximum	O
+length	O
+sequences	O
+(	O
+MLS	O
+)	O
+and	O
+Legendre	O
+sequences	O
+(	O
+LGS	O
+)	O
+.	O
+
+The	O
+pseudolymphoma	O
+syndrome	O
+is	O
+a	O
+reversible	O
+reactive	O
+condition	O
+consisting	O
+of	O
+fever	O
+,	O
+lymphadenopathy	O
+and	O
+generalized	O
+rash	O
+.	O
+
+In	O
+the	O
+local	O
+geomagnetic	O
+field	O
+,	O
+the	O
+animals	O
+preferred	O
+the	O
+SE	O
+-	O
+sector	O
+.	O
+
+In	O
+the	O
+artificial	O
+lung	O
+,	O
+like	O
+in	O
+the	O
+natural	O
+lung	O
+and	O
+peripheral	O
+tissues	O
+,	O
+gas	O
+exchanges	O
+depend	O
+on	O
+several	O
+parameters	O
+:	O
+blood	O
+inlet	O
+conditions	O
+,	O
+blood	O
+flow	O
+rate	O
+,	O
+temperature	O
+,	O
+composition	O
+of	O
+the	O
+gas	O
+mixture	O
+used	O
+for	O
+ventilation	O
+,	O
+blood	O
+tissue	O
+perfusion	O
+,	O
+O2	O
+consumption	O
+,	O
+etc	O
+.	O
+
+Mean	O
+(	O
++	O
+/	O
+-	O
+SE	O
+)	O
+measurements	O
+of	O
+clearance	O
+(	O
+24	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+.	O
+06	O
+v	O
+26	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+.	O
+05	O
+mL	O
+/	O
+min	O
+/	O
+m2	O
+)	O
+,	O
+half	O
+-	O
+life	O
+(	O
+5	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+v	O
+6	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+hours	O
+)	O
+,	O
+and	O
+volume	O
+of	O
+distribution	O
+(	O
+12	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+v	O
+13	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+6	O
+L	O
+/	O
+m2	O
+)	O
+were	O
+not	O
+significantly	O
+different	O
+in	O
+patients	O
+with	O
+jaundice	O
+when	O
+compared	O
+with	O
+controls	O
+.	O
+
+Attitudes	O
+were	O
+found	O
+to	O
+be	O
+multidimensional	O
+,	O
+with	O
+similar	O
+dimensions	O
+being	O
+identified	O
+in	O
+both	O
+samples	O
+.	O
+
+We	O
+conclude	O
+that	O
+DNA	O
+ploidy	O
+is	O
+a	O
+major	O
+objective	O
+prognostic	O
+factor	O
+and	O
+therapeutic	O
+determinant	O
+for	O
+endometrial	O
+carcinoma	O
+.	O
+
+A	O
+semiautomatic	O
+digital	O
+system	O
+(	O
+Videoplan	O
+2	O
+)	O
+was	O
+used	O
+.	O
+
+Environmental	O
+factors	O
+were	O
+more	O
+important	O
+in	O
+the	O
+older	O
+cohorts	O
+(	O
+perhaps	O
+because	O
+of	O
+less	O
+reliable	O
+recall	O
+)	O
+.	O
+
+Dopamine	O
+SERS	O
+spectra	O
+from	O
+these	O
+electrodes	O
+are	O
+similar	O
+to	O
+those	O
+obtained	O
+at	O
+uncoated	O
+electrodes	O
+.	O
+
+These	O
+findings	O
+indicate	O
+that	O
+hypergastrinemia	O
+induced	O
+by	O
+surgical	O
+removal	O
+of	O
+acid	O
+-	O
+producing	O
+mucosa	O
+in	O
+the	O
+rat	O
+has	O
+the	O
+same	O
+effects	O
+on	O
+oxyntical	O
+mucosal	B-GENE
+HDC	I-GENE
+activity	O
+,	O
+histamine	O
+concentration	O
+and	O
+ECL	O
+cell	O
+density	O
+as	O
+hypergastrinemia	O
+induced	O
+by	O
+continuous	O
+gastrin	B-GENE
+infusion	O
+or	O
+by	O
+long	O
+-	O
+term	O
+treatment	O
+with	O
+effective	O
+antisecretagogues	O
+.	O
+
+The	O
+order	O
+of	O
+the	O
+helicase	B-GENE
+motif	I-GENE
+and	O
+the	O
+nsP3	B-GENE
+homology	I-GENE
+region	I-GENE
+in	O
+the	O
+RUB	O
+genome	O
+is	O
+reversed	O
+with	O
+respect	O
+to	O
+the	O
+alphavirus	O
+genome	O
+indicating	O
+that	O
+a	O
+genetic	O
+rearrangement	O
+has	O
+occurred	O
+during	O
+the	O
+evolution	O
+of	O
+these	O
+viruses	O
+.	O
+
+The	O
+results	O
+suggest	O
+followings	O
+-	O
+-	O
+1	O
+)	O
+both	O
+eosinophils	O
+and	O
+neutrophils	O
+participate	O
+in	O
+hypersecretion	O
+of	O
+type	O
+Ib	O
+in	O
+atopic	O
+cases	O
+,	O
+and	O
+only	O
+eosinophils	O
+in	O
+non	O
+-	O
+atopic	O
+cases	O
+.	O
+
+There	O
+were	O
+5	O
+treatments	O
+:	O
+control	O
+(	O
+C	O
+)	O
+;	O
+a	O
+wooden	O
+surround	O
+in	O
+one	O
+rear	O
+corner	O
+of	O
+the	O
+cage	O
+(	O
+S	O
+)	O
+;	O
+a	O
+fiberglass	O
+rollaway	O
+hollow	O
+in	O
+one	O
+rear	O
+corner	O
+of	O
+the	O
+cage	O
+(	O
+H	O
+)	O
+;	O
+a	O
+hollow	O
+and	O
+a	O
+surround	O
+(	O
+H	O
+/	O
+S	O
+)	O
+;	O
+a	O
+nest	O
+box	O
+attached	O
+to	O
+the	O
+back	O
+of	O
+the	O
+cage	O
+,	O
+containing	O
+a	O
+hollow	O
+(	O
+N	O
+)	O
+.	O
+
+While	O
+no	O
+significant	O
+differences	O
+in	O
+the	O
+tensile	O
+responses	O
+or	O
+failure	O
+characteristics	O
+were	O
+noted	O
+for	O
+irradiated	O
+and	O
+nonirradiated	O
+grafts	O
+in	O
+the	O
+drip	O
+,	O
+in	O
+the	O
+bath	O
+environment	O
+the	O
+nonirradiated	O
+tissues	O
+had	O
+greater	O
+strength	O
+and	O
+modulus	O
+.	O
+
+The	O
+patient	O
+was	O
+treated	O
+with	O
+benzathine	O
+penicillin	O
+,	O
+2	O
+,	O
+400	O
+,	O
+000	O
+U	O
+weekly	O
+for	O
+three	O
+weeks	O
+.	O
+
+A	O
+consensus	O
+binding	O
+site	O
+for	O
+the	O
+transcription	O
+factor	O
+SP1	B-GENE
+was	O
+identified	O
+in	O
+intron	O
+As	O
+downstream	O
+of	O
+the	O
+proenkephalin	B-GENE
+germ	I-GENE
+cell	I-GENE
+cap	I-GENE
+site	I-GENE
+region	I-GENE
+.	O
+
+This	O
+proposed	O
+method	O
+is	O
+similar	O
+in	O
+principle	O
+to	O
+the	O
+sets	O
+technique	O
+but	O
+is	O
+shown	O
+to	O
+have	O
+much	O
+better	O
+expected	O
+time	O
+to	O
+alarm	O
+properties	O
+.	O
+
+Drug	O
+and	O
+personnel	O
+costs	O
+were	O
+reduced	O
+when	O
+batch	O
+manufacturing	O
+with	O
+40	O
+-	O
+mL	O
+multidose	O
+vials	O
+was	O
+compared	O
+with	O
+extemporaneous	O
+compounding	O
+with	O
+unit	O
+-	O
+dose	O
+vials	O
+.	O
+
+Changes	O
+in	O
+prognosis	O
+of	O
+twin	O
+births	O
+over	O
+20	O
+years	O
+.	O
+
+Dermal	O
+toxicity	O
+and	O
+carcinogenicity	O
+of	O
+4	O
+-	O
+vinyl	O
+-	O
+1	O
+-	O
+cyclohexene	O
+diepoxide	O
+in	O
+Fischer	O
+rats	O
+and	O
+B6C3F1	O
+mice	O
+.	O
+
+Per	O
+kg	O
+FFM	O
+SMR	O
+was	O
+almost	O
+restored	O
+to	O
+baseline	O
+values	O
+for	O
+the	O
+EX	O
+group	O
+,	O
+whereas	O
+the	O
+non	O
+-	O
+exercising	O
+subjects	O
+still	O
+showed	O
+depressed	O
+values	O
+(	O
+EX	O
+3	O
+.	O
+7	O
+per	O
+cent	O
+and	O
+D	O
++	O
+DE	O
+15	O
+.	O
+8	O
+per	O
+cent	O
+lower	O
+than	O
+before	O
+treatment	O
+;	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+MK	O
+-	O
+927	O
+:	O
+a	O
+topically	O
+active	O
+ocular	O
+hypotensive	O
+carbonic	B-GENE
+anhydrase	I-GENE
+inhibitor	O
+.	O
+
+PCR	O
+-	O
+derived	O
+fragments	O
+were	O
+used	O
+as	O
+probes	O
+for	O
+the	O
+isolation	O
+of	O
+the	O
+U3	B-GENE
+snRNA	I-GENE
+genes	I-GENE
+from	O
+a	O
+genomic	O
+library	O
+of	O
+Arabidopsis	O
+.	O
+
+The	O
+transcriptional	O
+unit	O
+spans	O
+a	O
+chromosomal	O
+region	O
+of	O
+about	O
+55	O
+kilobase	O
+pairs	O
+(	O
+kbp	O
+)	O
+.	O
+
+100	O
+of	O
+the	O
+patients	O
+who	O
+would	O
+have	O
+died	O
+survive	O
+.	O
+
+The	O
+effects	O
+of	O
+tap	O
+(	O
+TW	O
+)	O
+or	O
+carbonated	O
+(	O
+CW	O
+)	O
+water	O
+on	O
+arterial	O
+pH	O
+,	O
+partial	O
+pressure	O
+of	O
+carbon	O
+dioxide	O
+(	O
+PCO2	O
+)	O
+and	O
+plasma	O
+lactate	O
+were	O
+determined	O
+in	O
+heat	O
+-	O
+stressed	O
+broilers	O
+.	O
+
+Transient	O
+expression	O
+of	O
+human	B-GENE
+and	I-GENE
+chicken	I-GENE
+progesterone	I-GENE
+receptors	I-GENE
+does	O
+not	O
+support	O
+alternative	O
+translational	O
+initiation	O
+from	O
+a	O
+single	O
+mRNA	O
+as	O
+the	O
+mechanism	O
+generating	O
+two	O
+receptor	O
+isoforms	O
+.	O
+
+The	O
+Community	O
+Adjustment	O
+Scale	O
+provided	O
+outcome	O
+data	O
+related	O
+to	O
+the	O
+subjects	O
+'	O
+degree	O
+of	O
+productivity	O
+,	O
+ability	O
+to	O
+maintain	O
+close	O
+relationships	O
+,	O
+and	O
+presence	O
+/	O
+absence	O
+of	O
+symptomatology	O
+an	O
+average	O
+of	O
+32	O
+years	O
+after	O
+initial	O
+admission	O
+.	O
+
+However	O
+,	O
+at	O
+18	O
+months	O
+of	O
+age	O
+,	O
+significantly	O
+higher	O
+levels	O
+of	O
+IgG1	B-GENE
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+of	O
+IgG4	B-GENE
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+were	O
+found	O
+in	O
+infants	O
+with	O
+an	O
+elevated	O
+IgE	B-GENE
+(	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+8	O
+.	O
+0	O
+kU	O
+/	O
+l	O
+)	O
+than	O
+in	O
+those	O
+with	O
+a	O
+lower	O
+level	O
+.	O
+
+The	O
+protein	O
+sequence	O
+contains	O
+seven	O
+potential	O
+N	O
+-	O
+linked	O
+glycosylation	O
+sites	O
+and	O
+a	O
+threonine	O
+/	O
+serine	O
+-	O
+rich	O
+region	O
+which	O
+is	O
+a	O
+potential	O
+site	O
+for	O
+attachment	O
+of	O
+O	O
+-	O
+linked	O
+carbohydrate	O
+.	O
+
+Thus	O
+adaptation	O
+to	O
+continuous	O
+mild	O
+stress	O
+has	O
+a	O
+potent	O
+antiarrhythmic	O
+effect	O
+which	O
+occurs	O
+due	O
+to	O
+the	O
+increased	O
+vagal	O
+tone	O
+.	O
+
+The	O
+eluent	O
+from	O
+the	O
+column	O
+was	O
+mixed	O
+with	O
+the	O
+chemiluminescent	O
+solution	O
+containing	O
+lucigenin	B-GENE
+and	O
+Triton	O
+X	O
+-	O
+100	O
+and	O
+a	O
+0	O
+.	O
+28	O
+M	O
+KOH	O
+solution	O
+by	O
+pumps	O
+and	O
+monitored	O
+by	O
+a	O
+chemiluminescence	O
+detector	O
+.	O
+
+On	O
+histologic	O
+examination	O
+the	O
+cuboidal	O
+epithelium	O
+of	O
+the	O
+mucous	O
+membrane	O
+was	O
+found	O
+to	O
+be	O
+changed	O
+into	O
+columnar	O
+epithelium	O
+,	O
+with	O
+uneven	O
+distribution	O
+of	O
+enlarged	O
+nuclei	O
+in	O
+the	O
+vacuolized	O
+cytoplasm	O
+.	O
+
+These	O
+results	O
+suggest	O
+an	O
+increased	O
+risk	O
+of	O
+developing	O
+cancer	O
+among	O
+polyp	O
+patients	O
+and	O
+the	O
+possibility	O
+of	O
+prophylactic	O
+effect	O
+of	O
+polypectomy	O
+against	O
+subsequent	O
+cancer	O
+.	O
+
+The	O
+same	O
+trend	O
+was	O
+noted	O
+between	O
+YG	O
+4	O
+.	O
+5	O
+heifers	O
+and	O
+YG	O
+5	O
+.	O
+5	O
+steers	O
+,	O
+indicating	O
+a	O
+sex	O
+-	O
+related	O
+deposition	O
+of	O
+seam	O
+fat	O
+in	O
+fed	O
+cattle	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+consists	O
+of	O
+48	O
+bp	O
+of	O
+5	O
+'	O
+-	O
+end	O
+non	O
+-	O
+coding	O
+region	O
+,	O
+1695	O
+bp	O
+of	O
+coding	O
+region	O
+and	O
+212	O
+bp	O
+of	O
+3	O
+'	O
+-	O
+end	O
+non	O
+-	O
+coding	O
+region	O
+including	O
+a	O
+20	O
+bp	O
+poly	O
+(	O
+A	O
+)	O
+tail	O
+.	O
+
+Toxicities	O
+included	O
+:	O
+nausea	O
+/	O
+vomiting	O
+(	O
+69	O
+%	O
+)	O
+,	O
+headache	O
+(	O
+25	O
+%	O
+)	O
+,	O
+chills	O
+(	O
+69	O
+%	O
+)	O
+,	O
+pain	O
+at	O
+tumor	O
+sites	O
+(	O
+63	O
+%	O
+)	O
+,	O
+hypotension	O
+(	O
+31	O
+%	O
+)	O
+,	O
+and	O
+hypertension	O
+(	O
+38	O
+%	O
+)	O
+.	O
+
+The	O
+results	O
+also	O
+showed	O
+that	O
+although	O
+oyster	O
+shell	O
+supplementation	O
+generally	O
+increased	O
+alkaline	B-GENE
+phosphatase	I-GENE
+activity	O
+,	O
+bone	O
+mineralization	O
+was	O
+relatively	O
+uninfluenced	O
+as	O
+judged	O
+by	O
+the	O
+low	O
+coefficients	O
+of	O
+variation	O
+(	O
+CV	O
+)	O
+of	O
+3	O
+.	O
+14	O
+-	O
+3	O
+.	O
+51	O
+%	O
+and	O
+3	O
+.	O
+39	O
+-	O
+4	O
+.	O
+82	O
+%	O
+for	O
+calcium	O
+and	O
+phosphorus	O
+content	O
+in	O
+the	O
+femur	O
+and	O
+tibia	O
+respectively	O
+.	O
+
+In	O
+6	O
+of	O
+24	O
+infants	O
+studied	O
+(	O
+27th	O
+-	O
+40th	O
+weeks	O
+of	O
+gestation	O
+)	O
+,	O
+acquired	O
+and	O
+congenital	O
+structural	O
+anomalies	O
+of	O
+the	O
+airways	O
+were	O
+detected	O
+with	O
+an	O
+ultrathin	O
+flexible	O
+fiberscope	O
+(	O
+Olympus	O
+PF18	O
+S	O
+,	O
+1	O
+.	O
+8	O
+mm	O
+)	O
+.	O
+
+Fatal	O
+encephalitis	O
+in	O
+a	O
+patient	O
+with	O
+chronic	O
+graft	O
+-	O
+versus	O
+-	O
+host	O
+disease	O
+.	O
+
+Compared	O
+to	O
+its	O
+counterpart	O
+in	O
+the	O
+GPB	B-GENE
+gene	I-GENE
+,	O
+exon	O
+3	O
+of	O
+the	O
+GPE	B-GENE
+gene	I-GENE
+contains	O
+several	O
+point	O
+mutations	O
+,	O
+an	O
+insertion	O
+of	O
+24	O
+bp	O
+,	O
+and	O
+a	O
+stop	O
+codon	O
+which	O
+shortens	O
+the	O
+reading	O
+frame	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+a	O
+cDNA	O
+encoding	O
+rat	B-GENE
+NADH	I-GENE
+-	I-GENE
+cytochrome	I-GENE
+b5	I-GENE
+reductase	I-GENE
+and	O
+the	O
+corresponding	O
+gene	O
+.	O
+
+The	O
+results	O
+corroborate	O
+the	O
+idea	O
+that	O
+the	O
+structure	O
+of	O
+relaxation	O
+curves	O
+contains	O
+information	O
+on	O
+the	O
+distance	O
+scale	O
+and	O
+on	O
+the	O
+architecture	O
+of	O
+the	O
+pore	O
+space	O
+,	O
+even	O
+if	O
+it	O
+is	O
+difficult	O
+to	O
+extract	O
+it	O
+without	O
+ambiguities	O
+.	O
+
+Serotonin	B-GENE
+5	I-GENE
+-	I-GENE
+HT2	I-GENE
+receptor	I-GENE
+binding	O
+on	O
+blood	O
+platelets	O
+as	O
+a	O
+state	O
+dependent	O
+marker	O
+in	O
+major	O
+affective	O
+disorder	O
+.	O
+
+Although	O
+%	O
+BF	O
+was	O
+correlated	O
+with	O
+all	O
+the	O
+BMIs	O
+(	O
+r	O
+=	O
+0	O
+.	O
+60	O
+-	O
+0	O
+.	O
+82	O
+)	O
+,	O
+applying	O
+objective	O
+definitions	O
+of	O
+obesity	O
+based	O
+on	O
+BMIs	O
+or	O
+%	O
+BF	O
+by	O
+densitometry	O
+often	O
+produced	O
+conflicting	O
+results	O
+.	O
+
+The	O
+RF	O
+values	O
+correlated	O
+well	O
+with	O
+the	O
+angiographic	O
+semiquantitative	O
+scale	O
+of	O
+severity	O
+of	O
+aortal	O
+insufficiency	O
+(	O
+r	O
+=	O
+0	O
+.	O
+805	O
+;	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+,	O
+although	O
+they	O
+enabled	O
+the	O
+authors	O
+only	O
+to	O
+make	O
+a	O
+partial	O
+differentiation	O
+of	O
+haemodynamically	O
+severe	O
+regurgitations	O
+and	O
+mild	O
+or	O
+insignificant	O
+ones	O
+.	O
+
+Promoter	O
+elements	O
+include	O
+an	O
+atypical	O
+TATA	O
+box	O
+(	O
+GTTA	O
+)	O
+,	O
+one	O
+CCAAT	O
+box	O
+much	O
+further	O
+from	O
+the	O
+initiation	O
+site	O
+,	O
+three	O
+reverse	O
+compliments	O
+of	O
+CCAAT	O
+(	O
+ATTGG	O
+)	O
+,	O
+and	O
+two	O
+pyrimidine	O
+-	O
+rich	O
+nucleotide	O
+stretches	O
+.	O
+
+The	O
+cloned	O
+genes	O
+were	O
+identified	O
+in	O
+genetic	O
+libraries	O
+by	O
+hybridization	O
+screening	O
+using	O
+four	O
+deoxyoligonucleotide	O
+probes	O
+which	O
+corresponded	O
+to	O
+the	O
+partial	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+purified	O
+enzyme	O
+.	O
+
+The	O
+pattern	O
+for	O
+catalytic	O
+zinc	O
+sites	O
+included	O
+two	O
+ligands	O
+close	O
+in	O
+sequence	O
+,	O
+a	O
+sequence	O
+-	O
+distant	O
+ligand	O
+,	O
+and	O
+a	O
+main	O
+-	O
+chain	O
+hydrogen	O
+bond	O
+joining	O
+two	O
+ligands	O
+.	O
+
+Results	O
+of	O
+the	O
+long	O
+-	O
+term	O
+observation	O
+and	O
+treatment	O
+of	O
+patients	O
+with	O
+arterial	O
+hypertension	O
+
+Eucaryotic	O
+transcription	O
+factors	O
+that	O
+stimulate	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+by	O
+increasing	O
+the	O
+efficiency	O
+of	O
+elongation	O
+of	O
+specifically	O
+or	O
+randomly	O
+initiated	O
+RNA	O
+chains	O
+have	O
+been	O
+isolated	O
+and	O
+characterized	O
+.	O
+
+Sprague	O
+-	O
+Dawley	O
+newborn	O
+rats	O
+(	O
+n	O
+=	O
+85	O
+)	O
+breathed	O
+100	O
+%	O
+oxygen	O
+(	O
+O2	O
+)	O
+or	O
+room	O
+air	O
+(	O
+RA	O
+)	O
+during	O
+the	O
+first	O
+8	O
+days	O
+of	O
+life	O
+,	O
+and	O
+then	O
+RA	O
+.	O
+
+The	O
+Lm	O
+increased	O
+and	O
+the	O
+alveoli	O
+/	O
+mm2	O
+and	O
+elastic	O
+recoil	O
+pressure	O
+decreased	O
+.	O
+
+In	O
+Experiment	O
+II	O
+,	O
+as	O
+performing	O
+moderate	O
+supine	O
+cycling	O
+(	O
+55	O
+%	O
+VO2	O
+max	O
+)	O
+for	O
+50	O
+minutes	O
+under	O
+several	O
+LBNP	O
+conditions	O
+in	O
+5	O
+sedentary	O
+women	O
+,	O
+there	O
+were	O
+correspondingly	O
+similar	O
+changing	O
+manners	O
+of	O
+the	O
+cardiovascular	O
+adjustments	O
+to	O
+each	O
+of	O
+the	O
+phases	O
+given	O
+in	O
+Experiment	O
+I	O
+.	O
+
+Commercially	O
+available	O
+formulations	O
+of	O
+2	O
+.	O
+5	O
+%	O
+and	O
+5	O
+%	O
+lambdacyhalothrin	O
+can	O
+be	O
+diluted	O
+either	O
+with	O
+water	O
+for	O
+ULV	O
+cold	O
+aerosol	O
+space	O
+-	O
+spraying	O
+or	O
+with	O
+diesel	O
+/	O
+kerosene	O
+for	O
+thermal	O
+fogging	O
+at	O
+recommended	O
+application	O
+rates	O
+of	O
+0	O
+.	O
+5	O
+-	O
+1	O
+g	O
+ai	O
+/	O
+ha	O
+for	O
+mosquito	O
+control	O
+and	O
+2	O
+g	O
+ai	O
+/	O
+ha	O
+for	O
+housefly	O
+control	O
+.	O
+
+Thus	O
+,	O
+this	O
+reading	O
+frame	O
+was	O
+concluded	O
+to	O
+encode	O
+the	O
+precursor	O
+of	O
+mitochondrial	B-GENE
+fumarase	I-GENE
+.	O
+
+Sequence	O
+analysis	O
+indicates	O
+that	O
+in	O
+addition	O
+to	O
+an	O
+ATA	O
+and	O
+GC	O
+box	O
+,	O
+this	O
+region	O
+contains	O
+domains	O
+that	O
+have	O
+been	O
+implicated	O
+in	O
+the	O
+regulation	O
+of	O
+other	O
+muscle	O
+-	O
+specific	O
+genes	O
+:	O
+a	O
+CArG	O
+box	O
+at	O
+-	O
+91	O
+bp	O
+;	O
+myocyte	B-GENE
+-	I-GENE
+specific	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+nuclear	I-GENE
+factor	I-GENE
+1	I-GENE
+binding	I-GENE
+site	I-GENE
+homologies	O
+at	O
+-	O
+58	O
+,	O
+-	O
+535	O
+,	O
+and	O
+-	O
+583	O
+bp	O
+;	O
+and	O
+a	O
+muscle	O
+-	O
+CAAT	O
+consensus	O
+sequence	O
+at	O
+-	O
+394	O
+bp	O
+relative	O
+to	O
+the	O
+cap	O
+site	O
+.	O
+
+The	O
+trk	B-GENE
+-	I-GENE
+2h	I-GENE
+oncogene	I-GENE
+,	O
+isolated	O
+from	O
+the	O
+human	O
+breast	O
+carcinoma	O
+cell	O
+line	O
+MDA	O
+-	O
+MB	O
+231	O
+by	O
+genomic	O
+DNA	O
+-	O
+transfection	O
+into	O
+NIH3T3	O
+cells	O
+,	O
+consists	O
+of	O
+the	O
+trk	B-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+receptor	I-GENE
+kinase	I-GENE
+domain	I-GENE
+fused	O
+to	O
+a	O
+N	O
+-	O
+terminal	O
+41	O
+amino	O
+acid	O
+activating	O
+sequence	O
+(	O
+Kozma	O
+,	O
+S	O
+.	O
+C	O
+.	O
+,	O
+Redmond	O
+,	O
+S	O
+.	O
+M	O
+.	O
+S	O
+.	O
+,	O
+Xiao	O
+-	O
+Chang	O
+,	O
+F	O
+.	O
+,	O
+Saurer	O
+,	O
+S	O
+.	O
+M	O
+.	O
+,	O
+Groner	O
+,	O
+B	O
+.	O
+and	O
+Hynes	O
+,	O
+N	O
+.	O
+E	O
+.	O
+
+Antibodies	O
+raised	O
+against	O
+a	O
+bacterially	O
+produced	O
+beta	B-GENE
+gal	I-GENE
+-	O
+trk	B-GENE
+receptor	O
+kinase	O
+fusion	O
+protein	O
+recognized	O
+a	O
+44	O
+kd	O
+phosphoprotein	O
+phosphorylated	O
+on	O
+serine	O
+,	O
+threonine	O
+and	O
+tyrosine	O
+in	O
+extracts	O
+of	O
+trk	B-GENE
+-	I-GENE
+2h	I-GENE
+transformed	O
+NIH3T3	O
+cells	O
+.	O
+
+Since	O
+very	O
+recent	O
+scanning	O
+-	O
+deletion	O
+analysis	O
+indicates	O
+that	O
+there	O
+is	O
+a	O
+critical	O
+region	O
+for	O
+activity	O
+near	O
+Cys	O
+-	O
+118	O
+and	O
+that	O
+Cys	O
+-	O
+118	O
+is	O
+necessary	O
+for	O
+maximal	O
+activity	O
+,	O
+we	O
+conclude	O
+that	O
+the	O
+Cys	O
+-	O
+118	O
+residue	O
+is	O
+necessary	O
+for	O
+proper	O
+glycosylation	O
+and	O
+maximal	O
+biologic	O
+activity	O
+of	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+.	O
+
+Molecular	O
+and	O
+functional	O
+characterization	O
+of	O
+the	O
+promoter	O
+of	O
+ETS2	B-GENE
+,	O
+the	O
+human	O
+c	B-GENE
+-	I-GENE
+ets	I-GENE
+-	I-GENE
+2	I-GENE
+gene	O
+.	O
+
+Information	O
+about	O
+immunologic	O
+drug	O
+interactions	O
+is	O
+needed	O
+by	O
+pharmacists	O
+to	O
+make	O
+rational	O
+drug	O
+-	O
+use	O
+decisions	O
+.	O
+
+Branch	O
+occlusion	O
+of	O
+Heubner	O
+'	O
+s	O
+artery	O
+,	O
+or	O
+perforators	O
+from	O
+the	O
+proximal	O
+anterior	O
+or	O
+middle	O
+cerebral	O
+arteries	O
+were	O
+the	O
+posited	O
+mechanism	O
+of	O
+infarction	O
+.	O
+
+All	O
+ABFI	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+,	O
+regardless	O
+of	O
+origin	O
+,	O
+provided	O
+weak	O
+UAS	O
+function	O
+in	O
+vivo	O
+when	O
+examined	O
+in	O
+test	O
+plasmids	O
+.	O
+
+An	O
+examination	O
+of	O
+the	O
+properties	O
+of	O
+sequences	O
+surrounding	O
+ARS1	O
+left	O
+open	O
+the	O
+possibility	O
+that	O
+ABFI	B-GENE
+enhances	O
+the	O
+initiation	O
+of	O
+DNA	O
+replication	O
+at	O
+ARS1	O
+by	O
+transcriptional	O
+activation	O
+.	O
+
+Likewise	O
+,	O
+whether	O
+or	O
+not	O
+the	O
+hypotensive	O
+action	O
+of	O
+converting	O
+enzyme	O
+inhibitors	O
+is	O
+age	O
+-	O
+related	O
+is	O
+as	O
+yet	O
+unknown	O
+.	O
+
+Polyclonal	O
+antiserum	O
+generated	O
+to	O
+the	O
+fusion	O
+protein	O
+was	O
+capable	O
+of	O
+detecting	O
+42	O
+-	O
+and	O
+46	O
+-	O
+kilodalton	O
+polypeptides	O
+from	O
+virus	O
+particles	O
+;	O
+both	O
+polypeptides	O
+were	O
+also	O
+shown	O
+to	O
+contain	O
+HBsAg	B-GENE
+determinants	I-GENE
+.	O
+
+Role	O
+of	O
+superoxide	B-GENE
+dismutase	I-GENE
+in	O
+cellular	O
+oxidative	O
+processes	O
+and	O
+method	O
+of	O
+its	O
+determination	O
+in	O
+biological	O
+materials	O
+
+At	O
+maximum	O
+photosensitivity	O
+the	O
+inhibitory	O
+amino	O
+acids	O
+gamma	O
+-	O
+aminobutyric	O
+acid	O
+and	O
+taurine	O
+were	O
+lower	O
+,	O
+and	O
+those	O
+of	O
+asparagine	O
+(	O
+metabolite	O
+of	O
+the	O
+excitatory	O
+amino	O
+acid	O
+aspartate	O
+)	O
+were	O
+higher	O
+,	O
+than	O
+when	O
+the	O
+animals	O
+were	O
+not	O
+photosensitive	O
+.	O
+
+The	O
+priming	O
+activity	O
+of	O
+DNA	O
+incised	O
+by	O
+either	O
+of	O
+the	O
+Drosophila	O
+enzymes	O
+can	O
+be	O
+enhanced	O
+,	O
+however	O
+,	O
+by	O
+an	O
+additional	O
+incubation	O
+with	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+endonuclease	I-GENE
+IV	I-GENE
+,	O
+which	O
+is	O
+known	O
+to	O
+cleave	O
+depurinated	O
+DNA	O
+on	O
+the	O
+5	O
+'	O
+-	O
+side	O
+of	O
+an	O
+apurinic	O
+site	O
+.	O
+
+A	O
+.	O
+
+Therefore	O
+,	O
+in	O
+conjunction	O
+with	O
+a	O
+positive	O
+pregnancy	O
+test	O
+and	O
+the	O
+patient	O
+'	O
+s	O
+clinical	O
+history	O
+,	O
+a	O
+severely	O
+depressed	O
+or	O
+absent	O
+serum	O
+PAPP	B-GENE
+-	I-GENE
+A	I-GENE
+level	O
+may	O
+aid	O
+in	O
+the	O
+diagnosis	O
+of	O
+extrauterine	O
+pregnancy	O
+.	O
+
+The	O
+levels	O
+of	O
+both	O
+MAP1	B-GENE
+-	I-GENE
+specific	I-GENE
+and	I-GENE
+MAP2	I-GENE
+-	I-GENE
+specific	I-GENE
+mRNAs	I-GENE
+decline	O
+in	O
+the	O
+postnatal	O
+developing	O
+brain	O
+;	O
+the	O
+level	O
+of	O
+MAP1	B-GENE
+-	I-GENE
+specific	I-GENE
+mRNA	I-GENE
+also	O
+increases	O
+slightly	O
+in	O
+rat	O
+PC12	O
+cells	O
+upon	O
+exposure	O
+to	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+.	O
+
+The	O
+cDNAs	O
+cross	O
+-	O
+hybridize	O
+with	O
+genomic	O
+sequences	O
+in	O
+rat	O
+,	O
+human	O
+,	O
+and	O
+chicken	O
+DNA	O
+,	O
+but	O
+not	O
+with	O
+DNA	O
+from	O
+frog	O
+,	O
+Drosophila	O
+,	O
+or	O
+sea	O
+urchin	O
+.	O
+
+Colorimetric	O
+method	O
+of	O
+determining	O
+glycerin	O
+in	O
+the	O
+blood	O
+
+Deletion	O
+analysis	O
+was	O
+carried	O
+out	O
+within	O
+a	O
+part	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+showing	O
+homology	O
+to	O
+the	O
+upstream	O
+region	O
+of	O
+the	O
+yeast	B-GENE
+CYC1	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+N1	O
+and	O
+P2	O
+were	O
+comparable	O
+in	O
+amplitude	O
+and	O
+both	O
+had	O
+prolonged	O
+refractory	O
+periods	O
+.	O
+
+Tolerance	O
+to	O
+fenfluramine	O
+anorexia	O
+:	O
+fact	O
+or	O
+fiction	O
+?	O
+Recent	O
+findings	O
+in	O
+this	O
+laboratory	O
+with	O
+regard	O
+to	O
+tolerance	O
+to	O
+fenfluramine	O
+anorexia	O
+are	O
+reviewed	O
+with	O
+respect	O
+to	O
+generality	O
+of	O
+the	O
+behavioural	O
+phenomenon	O
+.	O
+
+In	O
+30	O
+dogs	O
+the	O
+left	O
+limb	O
+(	O
+tail	O
+)	O
+of	O
+the	O
+pancreas	O
+was	O
+removed	O
+but	O
+left	O
+in	O
+the	O
+abdominal	O
+cavity	O
+after	O
+cessation	O
+of	O
+blood	O
+flow	O
+to	O
+produce	O
+warm	O
+ischemia	O
+for	O
+30	O
+,	O
+60	O
+,	O
+and	O
+120	O
+min	O
+(	O
+10	O
+dogs	O
+at	O
+each	O
+time	O
+point	O
+)	O
+,	O
+and	O
+then	O
+was	O
+flushed	O
+with	O
+cold	O
+Ringers	O
+'	O
+lactate	O
+and	O
+transplanted	O
+to	O
+the	O
+iliac	O
+vessels	O
+.	O
+
+Furthermore	O
+,	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+sensitivity	O
+appears	O
+to	O
+be	O
+unaltered	O
+in	O
+BHT	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+the	O
+negative	O
+inotropic	O
+action	O
+of	O
+nicorandil	O
+is	O
+caused	O
+by	O
+inhibition	O
+of	O
+Ca	O
+influx	O
+and	O
+intracellular	O
+mobilization	O
+of	O
+Ca	O
+.	O
+
+Comparison	O
+of	O
+elastase	B-GENE
+-	I-GENE
+1	I-GENE
+with	O
+amylase	B-GENE
+,	O
+lipase	B-GENE
+,	O
+and	O
+trypsin	B-GENE
+-	O
+like	O
+immunoreactivity	O
+in	O
+the	O
+diagnosis	O
+of	O
+acute	O
+pancreatitis	O
+.	O
+
+A	O
+probe	O
+evoked	O
+potentials	O
+procedure	O
+was	O
+used	O
+to	O
+assess	O
+the	O
+relative	O
+engagement	O
+of	O
+both	O
+cerebral	O
+hemispheres	O
+during	O
+a	O
+language	O
+task	O
+in	O
+the	O
+following	O
+four	O
+groups	O
+of	O
+dextral	O
+adults	O
+:	O
+left	O
+hemisphere	O
+(	O
+LH	O
+)	O
+-	O
+damaged	O
+aphasics	O
+recovering	O
+from	O
+stroke	O
+,	O
+dysarthrics	O
+,	O
+right	O
+hemisphere	O
+(	O
+RH	O
+)	O
+-	O
+damaged	O
+nonaphasic	O
+patients	O
+,	O
+and	O
+normal	O
+control	O
+subjects	O
+.	O
+
+Mucolipidosis	O
+type	O
+IV	O
+:	O
+clinical	O
+spectrum	O
+and	O
+natural	O
+history	O
+.	O
+
+Two	O
+of	O
+the	O
+three	O
+groups	O
+were	O
+administered	O
+dauricine	O
+,	O
+as	O
+a	O
+new	O
+calcium	O
+channel	O
+blocker	O
+,	O
+and	O
+verapamil	O
+,	O
+as	O
+a	O
+generally	O
+recognized	O
+calcium	O
+channel	O
+blocker	O
+,	O
+respectively	O
+,	O
+from	O
+15	O
+minutes	O
+pre	O
+-	O
+bypass	O
+to	O
+the	O
+end	O
+of	O
+the	O
+bypass	O
+procedure	O
+(	O
+a	O
+period	O
+of	O
+95	O
+minutes	O
+)	O
+.	O
+
+No	O
+reflow	O
+occurred	O
+in	O
+approximately	O
+30	O
+percent	O
+of	O
+the	O
+muscle	O
+microvasculature	O
+upon	O
+reperfusion	O
+.	O
+
+Lysozyme	B-GENE
+activity	O
+was	O
+evidently	O
+increased	O
+as	O
+well	O
+in	O
+undiluted	O
+as	O
+in	O
+diluted	O
+sera	O
+in	O
+all	O
+our	O
+tested	O
+patients	O
+.	O
+
+The	O
+first	O
+involved	O
+measurements	O
+of	O
+the	O
+steady	O
+state	O
+levels	O
+of	O
+mRNAs	O
+for	O
+subunit	O
+5	O
+of	O
+cytochrome	B-GENE
+oxidase	I-GENE
+and	O
+the	O
+beta	O
+subunit	O
+of	O
+F1	B-GENE
+ATPase	I-GENE
+in	O
+wild	O
+type	O
+and	O
+in	O
+a	O
+hem2	B-GENE
+mutant	I-GENE
+.	O
+
+A	O
+5	B-GENE
+.	I-GENE
+8S	I-GENE
+-	I-GENE
+like	I-GENE
+structure	I-GENE
+is	O
+present	O
+within	O
+the	O
+5	O
+'	O
+-	O
+terminal	O
+region	O
+of	O
+all	O
+three	O
+fungal	B-GENE
+mitochondrial	I-GENE
+LSU	I-GENE
+rRNAs	I-GENE
+;	O
+in	O
+contrast	O
+,	O
+no	O
+4	B-GENE
+.	I-GENE
+5S	I-GENE
+-	I-GENE
+like	I-GENE
+structure	I-GENE
+is	O
+evident	O
+at	O
+the	O
+3	O
+'	O
+end	O
+of	O
+these	O
+molecules	O
+.	O
+
+The	O
+recovery	O
+of	O
+labelled	O
+methoxydextrane	O
+is	O
+98	O
++	O
+/	O
+-	O
+7	O
+%	O
+.	O
+
+ASL	O
+-	O
+8123	O
+demonstrated	O
+weak	O
+competitive	O
+beta	B-GENE
+-	I-GENE
+adrenoreceptor	I-GENE
+blocking	O
+activity	O
+in	O
+isolated	O
+guinea	O
+pig	O
+right	O
+atria	O
+with	O
+a	O
+pA2	O
+of	O
+3	O
+.	O
+73	O
++	O
+/	O
+-	O
+0	O
+.	O
+07	O
+;	O
+no	O
+agonist	O
+-	O
+like	O
+activity	O
+was	O
+observed	O
+in	O
+this	O
+tissue	O
+at	O
+concentrations	O
+of	O
+ASL	O
+-	O
+8123	O
+from	O
+3	O
+X	O
+10	O
+(	O
+-	O
+5	O
+)	O
+to	O
+1	O
+X	O
+10	O
+(	O
+-	O
+2	O
+)	O
+M	O
+.	O
+
+We	O
+discuss	O
+the	O
+results	O
+in	O
+relation	O
+to	O
+previous	O
+systems	O
+for	O
+parcellating	O
+the	O
+posterior	O
+ectosylvian	O
+gyrus	O
+of	O
+the	O
+cat	O
+and	O
+consider	O
+the	O
+possibility	O
+that	O
+divisions	O
+of	O
+the	O
+feline	O
+posterior	O
+ectosylvian	O
+gyrus	O
+correspond	O
+directly	O
+to	O
+areas	O
+making	O
+up	O
+the	O
+superior	O
+temporal	O
+gyrus	O
+in	O
+primates	O
+.	O
+
+The	O
+4	O
+-	O
+AP	O
+(	O
+4	O
+-	O
+20	O
+mM	O
+)	O
+effect	O
+resulted	O
+in	O
+a	O
+decrease	O
+of	O
+the	O
+sensory	O
+activity	O
+,	O
+which	O
+was	O
+fully	O
+restored	O
+by	O
+TEA	O
+or	O
+Ba2	O
++	O
+.	O
+
+Hybridization	O
+of	O
+a	O
+probe	O
+from	O
+this	O
+region	O
+to	O
+electrophoretic	O
+blots	O
+of	O
+RNAs	O
+from	O
+different	O
+human	O
+tissues	O
+showed	O
+a	O
+predominant	O
+2	O
+.	O
+8	O
+-	O
+kilobase	O
+(	O
+kb	O
+)	O
+message	O
+accompanied	O
+by	O
+weaker	O
+bands	O
+4	O
+.	O
+1	O
+and	O
+2	O
+.	O
+1	O
+kb	O
+in	O
+size	O
+.	O
+
+Prognosis	O
+of	O
+asymptomatic	O
+multiple	O
+myeloma	O
+.	O
+
+A	O
+new	O
+method	O
+for	O
+the	O
+quantitative	O
+analysis	O
+of	O
+sleep	O
+spindles	O
+during	O
+continuous	O
+overnight	O
+EEG	O
+recordings	O
+.	O
+
+Svensson	O
+et	O
+al	O
+.	O
+
+Endogenous	O
+release	O
+of	O
+neuronal	O
+serotonin	O
+and	O
+5	O
+-	O
+hydroxyindoleacetic	O
+acid	O
+in	O
+the	O
+caudate	O
+-	O
+putamen	O
+of	O
+the	O
+rat	O
+as	O
+revealed	O
+by	O
+intracerebral	O
+dialysis	O
+coupled	O
+to	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatography	O
+with	O
+fluorimetric	O
+detection	O
+.	O
+
+In	O
+this	O
+report	O
+we	O
+describe	O
+for	O
+the	O
+first	O
+time	O
+the	O
+complete	O
+primary	O
+structure	O
+of	O
+type	B-GENE
+X	I-GENE
+collagen	I-GENE
+,	O
+based	O
+on	O
+cloning	O
+and	O
+sequencing	O
+of	O
+cDNA	O
+and	O
+genomic	O
+DNA	O
+.	O
+
+Viable	O
+flap	O
+areas	O
+were	O
+established	O
+following	O
+vascular	O
+pedicle	O
+ligation	O
+(	O
+both	O
+vessels	O
+or	O
+only	O
+artery	O
+or	O
+vein	O
+)	O
+,	O
+on	O
+the	O
+third	O
+day	O
+after	O
+flap	O
+replantation	O
+in	O
+both	O
+island	O
+and	O
+free	O
+flaps	O
+.	O
+
+The	O
+size	O
+discrepancy	O
+is	O
+not	O
+due	O
+to	O
+glycosylation	O
+or	O
+phosphorylation	O
+of	O
+Ag35	B-GENE
+but	O
+may	O
+result	O
+from	O
+a	O
+proline	O
+-	O
+rich	O
+sequence	O
+which	O
+occurs	O
+in	O
+this	O
+polypeptide	O
+.	O
+
+A	O
+9	O
+.	O
+5	O
+-	O
+kb	O
+KpnI	B-GENE
+-	O
+SalI	B-GENE
+fragment	O
+,	O
+where	O
+all	O
+the	O
+DNA	O
+changes	O
+associated	O
+with	O
+su	B-GENE
+(	I-GENE
+Hw	I-GENE
+)	I-GENE
+mutations	I-GENE
+were	O
+mapped	O
+,	O
+was	O
+able	O
+to	O
+rescue	O
+the	O
+su	B-GENE
+(	I-GENE
+Hw	I-GENE
+)	I-GENE
+mutant	I-GENE
+phenotype	O
+after	O
+P	O
+-	O
+element	O
+-	O
+mediated	O
+germ	O
+-	O
+line	O
+transformation	O
+.	O
+
+The	O
+corticosterone	O
+synthesis	O
+inhibitor	O
+metyrapone	O
+(	O
+75	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+was	O
+given	O
+to	O
+attenuate	O
+the	O
+rise	O
+of	O
+corticosterone	O
+to	O
+a	O
+level	O
+typical	O
+of	O
+stressed	O
+males	O
+.	O
+
+The	O
+effects	O
+of	O
+L655	O
+,	O
+240	O
+,	O
+a	O
+selective	O
+thromboxane	O
+and	O
+prostaglandin	O
+endoperoxide	O
+antagonist	O
+,	O
+on	O
+ischemia	O
+-	O
+and	O
+reperfusion	O
+-	O
+induced	O
+cardiac	O
+arrhythmias	O
+.	O
+
+In	O
+10	O
+pentobarbitalized	O
+dogs	O
+,	O
+plasma	O
+viscosity	O
+(	O
+Ep	O
+)	O
+was	O
+raised	O
+fourfold	O
+while	O
+apparent	O
+blood	O
+viscosity	O
+(	O
+Ea	O
+)	O
+increased	O
+about	O
+twofold	O
+by	O
+two	O
+steps	O
+of	O
+exchange	O
+transfusion	O
+of	O
+200	O
+ml	O
+of	O
+plasma	O
+with	O
+plasma	O
+containing	O
+high	O
+molecular	O
+weight	O
+dextran	O
+(	O
+mol	O
+wt	O
+500	O
+,	O
+000	O
+,	O
+20	O
+%	O
+wt	O
+/	O
+vol	O
+)	O
+.	O
+
+The	O
+small	B-GENE
+IGF	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+is	O
+abundant	O
+in	O
+human	O
+amniotic	O
+fluid	O
+.	O
+
+Serum	O
+prostatic	B-GENE
+acid	I-GENE
+phosphatase	I-GENE
+levels	O
+showed	O
+a	O
+significantly	O
+weaker	O
+correlation	O
+with	O
+cancer	O
+volume	O
+(	O
+r	O
+equals	O
+0	O
+.	O
+51	O
+)	O
+and	O
+every	O
+other	O
+pathological	O
+parameter	O
+.	O
+
+The	O
+investigation	O
+was	O
+thereafter	O
+continued	O
+in	O
+an	O
+open	O
+fashion	O
+by	O
+administering	O
+a	O
+single	O
+10	O
+mg	O
+dose	O
+of	O
+the	O
+MAO	B-GENE
+-	I-GENE
+B	I-GENE
+inhibitor	O
+deprenyl	O
+to	O
+the	O
+same	O
+subjects	O
+.	O
+
+Their	O
+studies	O
+have	O
+revealed	O
+a	O
+considerable	O
+increase	O
+of	O
+CSF	B-GENE
+AP	I-GENE
+activity	O
+in	O
+purulent	O
+meningitides	O
+whereas	O
+in	O
+serous	O
+meningitides	O
+it	O
+grows	O
+negligibly	O
+.	O
+
+A	O
+cDNA	O
+encoding	O
+a	O
+new	O
+human	O
+lymphocyte	O
+cell	O
+surface	O
+molecule	O
+has	O
+been	O
+isolated	O
+and	O
+shown	O
+to	O
+identify	O
+a	O
+fourth	O
+member	O
+of	O
+a	O
+recently	O
+discovered	O
+family	O
+of	O
+adhesion	O
+proteins	O
+.	O
+
+Dopamine	O
+caused	O
+a	O
+prominent	O
+potassium	O
+efflux	O
+measured	O
+as	O
+86Rb	O
++	O
+efflux	O
+from	O
+control	O
+glands	O
+,	O
+but	O
+was	O
+without	O
+effect	O
+in	O
+denervated	O
+glands	O
+.	O
+
+This	O
+approach	O
+was	O
+examined	O
+utilizing	O
+the	O
+fetal	O
+protein	O
+,	O
+HGB	B-GENE
+F	I-GENE
+.	O
+
+The	O
+investigation	O
+was	O
+apt	O
+at	O
+studying	O
+the	O
+relationship	O
+between	O
+urinary	O
+metabolites	O
+of	O
+serotonin	O
+and	O
+catecholamine	O
+(	O
+5	O
+-	O
+HIAA	O
+and	O
+VMA	O
+)	O
+,	O
+T	O
+-	O
+cells	O
+(	O
+OKT3	B-GENE
++	I-GENE
+)	O
+,	O
+T	O
+-	O
+helper	O
+(	O
+OKT4	B-GENE
++	I-GENE
+)	O
+,	O
+T	O
+-	O
+suppressor	O
+(	O
+OKT8	B-GENE
++	I-GENE
+)	O
+and	O
+B	O
+-	O
+cells	O
+(	O
+EAC	O
+-	O
+rosette	O
+forming	O
+cells	O
+)	O
+in	O
+normal	O
+(	O
+10	O
+subjects	O
+,	O
+1	O
+female	O
+,	O
+9	O
+male	O
+,	O
+age	O
+21	O
++	O
+/	O
+-	O
+5	O
+years	O
+)	O
+and	O
+stress	O
+administered	O
+subjects	O
+(	O
+20	O
+subjects	O
+,	O
+3	O
+female	O
+,	O
+17	O
+male	O
+,	O
+age	O
+20	O
++	O
+/	O
+-	O
+4	O
+years	O
+)	O
+.	O
+
+Their	O
+hydropathic	O
+plots	O
+are	O
+very	O
+similar	O
+and	O
+both	O
+possess	O
+three	O
+hydrophobic	O
+segments	O
+that	O
+are	O
+likely	O
+alpha	O
+-	O
+helical	O
+transmembrane	O
+segments	O
+.	O
+
+Angiotensin	B-GENE
+converting	I-GENE
+enzyme	I-GENE
+inhibitors	O
+enhance	O
+the	O
+antihypertensive	O
+efficacy	O
+of	O
+diuretics	O
+and	O
+blunt	O
+or	O
+prevent	O
+adverse	O
+metabolic	O
+effects	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+significant	O
+reduction	O
+in	O
+blood	O
+pressure	O
+,	O
+the	O
+angiotensin	B-GENE
+converting	I-GENE
+enzyme	I-GENE
+(	O
+ACE	B-GENE
+)	O
+inhibitor	O
+ramipril	O
+caused	O
+a	O
+significant	O
+regression	O
+of	O
+pathologic	O
+left	O
+ventricular	O
+hypertrophy	O
+demonstrated	O
+by	O
+magnetic	O
+resonance	O
+imaging	O
+and	O
+echocardiography	O
+.	O
+
+The	O
+ratio	O
+of	O
+radioactivity	O
+in	O
+tumour	O
+compared	O
+with	O
+normal	O
+tissue	O
+(	O
+T	O
+:	O
+N	O
+ratio	O
+)	O
+was	O
+determined	O
+after	O
+simultaneously	O
+injecting	O
+microspheres	O
+into	O
+the	O
+portal	O
+and	O
+arterial	O
+circulation	O
+of	O
+each	O
+animal	O
+.	O
+
+The	O
+mRNA	O
+was	O
+converted	O
+to	O
+cDNA	O
+and	O
+amplified	O
+by	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+technique	O
+.	O
+
+Tissue	O
+necrosis	O
+was	O
+evaluated	O
+using	O
+triphenyltetrazolium	O
+staining	O
+and	O
+was	O
+related	O
+to	O
+two	O
+major	O
+baseline	O
+predictors	O
+of	O
+infarct	O
+size	O
+:	O
+anatomic	O
+risk	O
+zone	O
+size	O
+and	O
+coronary	O
+collateral	O
+flow	O
+.	O
+
+To	O
+study	O
+the	O
+retinal	O
+surface	O
+in	O
+the	O
+human	O
+eye	O
+in	O
+normal	O
+and	O
+diseased	O
+states	O
+we	O
+used	O
+laser	O
+scanning	O
+tomography	O
+.	O
+
+Previously	O
+,	O
+we	O
+reported	O
+the	O
+sequence	O
+of	O
+the	O
+gene	B-GENE
+encoding	I-GENE
+human	I-GENE
+K14	I-GENE
+(	O
+D	O
+.	O
+
+Cotransfection	O
+of	O
+either	O
+construct	O
+with	O
+plasmids	O
+encoding	O
+PKI	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+31	I-GENE
+)	I-GENE
+inhibits	O
+cAMP	O
+-	O
+stimulated	O
+but	O
+not	O
+basal	O
+-	O
+or	O
+phorbol	O
+ester	O
+-	O
+stimulated	O
+expression	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+revealed	O
+several	O
+GC	O
+boxes	O
+but	O
+no	O
+identifiable	O
+TATA	O
+box	O
+.	O
+
+The	O
+underlying	O
+cirrhosis	O
+was	O
+alcoholic	O
+in	O
+11	O
+(	O
+53	O
+.	O
+3	O
+%	O
+)	O
+,	O
+cryptogenic	O
+in	O
+5	O
+(	O
+23	O
+.	O
+8	O
+%	O
+)	O
+,	O
+and	O
+hepatitis	O
+B	O
+chronic	O
+infection	O
+related	O
+in	O
+5	O
+(	O
+23	O
+.	O
+8	O
+%	O
+)	O
+.	O
+
+Once	O
+P	B-GENE
+-	I-GENE
+450scc	I-GENE
+mRNA	I-GENE
+is	O
+induced	O
+as	O
+a	O
+consequence	O
+of	O
+the	O
+LH	B-GENE
+/	O
+hCG	B-GENE
+surge	O
+it	O
+is	O
+constitutively	O
+maintained	O
+by	O
+luteinized	O
+cells	O
+in	O
+vivo	O
+(	O
+0	O
+-	O
+4	O
+days	O
+)	O
+and	O
+in	O
+vitro	O
+(	O
+0	O
+-	O
+9	O
+days	O
+)	O
+in	O
+the	O
+absence	O
+of	O
+gonadotropins	B-GENE
+,	O
+is	O
+susceptible	O
+to	O
+modulation	O
+by	O
+prolactin	B-GENE
+and	O
+is	O
+no	O
+longer	O
+regulated	O
+by	O
+cAMP	O
+.	O
+
+Similarly	O
+,	O
+a	O
+human	O
+but	O
+not	O
+a	O
+bovine	B-GENE
+alpha	I-GENE
+transgene	I-GENE
+was	O
+expressed	O
+in	O
+placenta	O
+in	O
+transgenic	O
+mice	O
+.	O
+
+A	O
+rapid	O
+staining	O
+technique	O
+for	O
+Leishmania	O
+parasites	O
+in	O
+splenic	O
+aspirate	O
+smears	O
+.	O
+
+NIK	O
+-	O
+244	O
+suppressed	O
+coronary	O
+ligation	O
+-	O
+and	O
+digitalis	O
+-	O
+induced	O
+arrhythmias	O
+,	O
+and	O
+the	O
+minimum	O
+effective	O
+plasma	O
+concentrations	O
+for	O
+arrhythmias	O
+induced	O
+by	O
+24	O
+-	O
+h	O
+and	O
+48	O
+-	O
+h	O
+coronary	O
+ligation	O
+and	O
+digitalis	O
+were	O
+0	O
+.	O
+41	O
++	O
+/	O
+-	O
+0	O
+.	O
+10	O
+(	O
+by	O
+1	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+,	O
+0	O
+.	O
+70	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+(	O
+by	O
+1	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+,	O
+and	O
+0	O
+.	O
+21	O
++	O
+/	O
+-	O
+0	O
+.	O
+08	O
+(	O
+by	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+microgram	O
+/	O
+ml	O
+,	O
+respectively	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+of	O
+the	O
+mean	O
+,	O
+n	O
+=	O
+6	O
+)	O
+.	O
+
+In	O
+TNF	B-GENE
+-	O
+resistant	O
+T24	O
+bladder	O
+carcinoma	O
+cells	O
+,	O
+TNF	B-GENE
+failed	O
+to	O
+alter	O
+EGF	B-GENE
+-	I-GENE
+R	I-GENE
+tyrosine	B-GENE
+protein	I-GENE
+kinase	I-GENE
+activity	O
+although	O
+both	O
+EGF	B-GENE
+and	O
+phorbol	O
+ester	O
+were	O
+shown	O
+to	O
+modulate	O
+the	O
+enzymatic	O
+activity	O
+of	O
+the	O
+receptor	O
+in	O
+these	O
+cells	O
+.	O
+
+Thus	O
+,	O
+phosphodiesterase	O
+inhibitors	O
+that	O
+produce	O
+an	O
+opiate	O
+quasi	O
+-	O
+withdrawal	O
+syndrome	O
+potentiate	O
+interoceptive	O
+stimuli	O
+and	O
+weight	O
+loss	O
+associated	O
+with	O
+the	O
+withdrawal	O
+syndrome	O
+precipitated	O
+by	O
+naltrexone	O
+in	O
+morphine	O
+-	O
+dependent	O
+rats	O
+.	O
+
+The	O
+diagnostic	O
+value	O
+of	O
+blood	O
+serum	O
+and	O
+urinary	B-GENE
+amylase	I-GENE
+,	O
+lipase	B-GENE
+,	O
+and	O
+trypsin	B-GENE
+in	O
+exacerbations	O
+of	O
+chronic	O
+relapsing	O
+pancreatitis	O
+is	O
+discussed	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+the	O
+mechanism	O
+of	O
+action	O
+,	O
+two	O
+groups	O
+of	O
+inodilators	O
+are	O
+distinguished	O
+,	O
+the	O
+phosphodiesterase	O
+inhibitors	O
+and	O
+the	O
+dopaminergic	O
+agents	O
+.	O
+
+Structural	O
+organization	O
+and	O
+expression	O
+of	O
+the	O
+mouse	B-GENE
+estrogen	I-GENE
+receptor	I-GENE
+.	O
+
+Intravenous	O
+gamma	B-GENE
+globulins	I-GENE
+
+Following	O
+chondroitinase	B-GENE
+AC	I-GENE
+and	I-GENE
+ABC	I-GENE
+digestion	O
+,	O
+staining	O
+reactions	O
+suggested	O
+that	O
+the	O
+highest	O
+levels	O
+of	O
+dermatan	O
+sulfate	O
+were	O
+in	O
+the	O
+diabetes	O
+resistant	O
+group	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+compared	O
+to	O
+diabetic	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+compared	O
+to	O
+diabetes	O
+prone	O
+)	O
+and	O
+the	O
+highest	O
+levels	O
+of	O
+chondroitin	O
+sulfates	O
+were	O
+in	O
+the	O
+diabetes	O
+prone	O
+group	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Myocardial	O
+perfusion	O
+was	O
+evaluated	O
+using	O
+the	O
+enhanced	O
+gray	O
+level	O
+after	O
+contrast	O
+injection	O
+,	O
+and	O
+the	O
+level	O
+was	O
+compared	O
+with	O
+the	O
+morphology	O
+and	O
+degree	O
+of	O
+collateral	O
+development	O
+.	O
+
+Once	O
+NGF	B-GENE
+administration	O
+is	O
+proven	O
+effective	O
+it	O
+will	O
+be	O
+possible	O
+to	O
+develop	O
+alternative	O
+ways	O
+of	O
+NGF	B-GENE
+administration	O
+.	O
+
+During	O
+the	O
+program	O
+'	O
+s	O
+use	O
+at	O
+the	O
+RSNA	O
+meeting	O
+,	O
+the	O
+program	O
+selected	O
+the	O
+correct	O
+diagnosis	O
+in	O
+the	O
+top	O
+five	O
+22	O
+%	O
+of	O
+the	O
+time	O
+.	O
+
+Immunoglobulin	B-GENE
+light	I-GENE
+chain	I-GENE
+(	O
+IgL	B-GENE
+)	O
+diversity	O
+is	O
+generated	O
+in	O
+the	O
+chicken	O
+by	O
+recombination	O
+between	O
+the	O
+single	O
+functional	O
+variable	O
+(	O
+VL	B-GENE
+)	O
+and	O
+joining	O
+(	O
+JL	B-GENE
+)	O
+gene	O
+segments	O
+and	O
+subsequent	O
+somatic	O
+diversification	O
+of	O
+the	O
+rearranged	O
+VL	B-GENE
+region	O
+.	O
+
+The	O
+results	O
+were	O
+as	O
+follows	O
+:	O
+1	O
+)	O
+Total	O
+integrated	O
+EMG	O
+activity	O
+of	O
+FB	O
+group	O
+was	O
+approximately	O
+equal	O
+in	O
+any	O
+occluded	O
+position	O
+,	O
+whereas	O
+that	O
+of	O
+CG	O
+and	O
+GF	O
+group	O
+varied	O
+from	O
+position	O
+to	O
+position	O
+.	O
+
+Muscle	O
+action	O
+potential	O
+and	O
+masticatory	O
+rhythm	O
+of	O
+anterior	O
+temporal	O
+and	O
+masseter	O
+muscles	O
+in	O
+children	O
+and	O
+adults	O
+
+The	O
+thrombolytic	O
+effects	O
+of	O
+native	O
+tissue	B-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+(	O
+AK	B-GENE
+-	I-GENE
+124	I-GENE
+)	O
+on	O
+experimental	O
+canine	O
+coronary	O
+thrombosis	O
+.	O
+
+O2	O
+and	O
+CO2	O
+in	O
+the	O
+tracheostomy	O
+tube	O
+were	O
+continuously	O
+monitored	O
+by	O
+mass	O
+spectrometry	O
+using	O
+a	O
+special	O
+sample	O
+-	O
+hold	O
+phase	O
+-	O
+locked	O
+sampling	O
+technique	O
+.	O
+
+Enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+for	O
+screening	O
+aflatoxin	O
+B1	O
+in	O
+cottonseed	O
+products	O
+and	O
+mixed	O
+feed	O
+:	O
+collaborative	O
+study	O
+.	O
+
+However	O
+,	O
+experiments	O
+with	O
+S1	B-GENE
+mapping	O
+of	O
+in	O
+vivo	O
+transcripts	O
+,	O
+gene	O
+disruptions	O
+in	O
+the	O
+alpha	O
+region	O
+,	O
+and	O
+a	O
+single	O
+-	O
+copy	O
+transcriptional	O
+fusion	O
+vector	O
+all	O
+suggested	O
+that	O
+these	O
+possible	O
+promoters	O
+were	O
+largely	O
+inactive	O
+during	O
+logarithmic	O
+growth	O
+,	O
+that	O
+the	O
+major	O
+promoter	O
+for	O
+the	O
+alpha	O
+operon	O
+lay	O
+upstream	O
+from	O
+the	O
+region	O
+cloned	O
+,	O
+and	O
+that	O
+the	O
+genes	O
+in	O
+the	O
+IF1	B-GENE
+to	O
+L17	B-GENE
+interval	O
+were	O
+cotranscribed	O
+.	O
+
+Two	O
+specific	O
+DNA	O
+-	O
+protein	O
+complexes	O
+were	O
+identified	O
+in	O
+gel	O
+retardation	O
+assays	O
+using	O
+HeLa	O
+cell	O
+nuclear	O
+extracts	O
+and	O
+an	O
+oligonucleotide	O
+probe	O
+spanning	O
+the	O
+footprinted	O
+region	O
+.	O
+
+After	O
+transfection	O
+,	O
+specific	O
+TSH	B-GENE
+beta	I-GENE
+promoter	I-GENE
+activity	O
+was	O
+evident	O
+in	O
+both	O
+TRH	B-GENE
+-	O
+responsive	O
+pituitary	O
+-	O
+derived	O
+GH3	O
+and	O
+primary	O
+pituitary	O
+cell	O
+cultures	O
+.	O
+
+In	O
+transformed	O
+E	O
+.	O
+coli	O
+,	O
+constitutive	B-GENE
+CAT	I-GENE
+expression	O
+is	O
+maintained	O
+when	O
+as	O
+little	O
+as	O
+0	O
+.	O
+3	O
+kilobase	O
+of	O
+DNA	O
+from	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+1	O
+.	O
+6	O
+-	O
+kilobase	O
+segment	O
+is	O
+inserted	O
+in	O
+the	O
+correct	O
+orientation	O
+in	O
+front	O
+of	O
+the	O
+CAT	B-GENE
+gene	I-GENE
+.	O
+
+Lowering	O
+of	O
+the	O
+renal	O
+blood	O
+flow	O
+alters	O
+the	O
+glomerular	O
+and	O
+tubular	O
+excretion	O
+processes	O
+.	O
+
+Tonometry	O
+of	O
+blood	O
+samples	O
+from	O
+patients	O
+may	O
+also	O
+be	O
+used	O
+in	O
+the	O
+determination	O
+of	O
+acid	O
+-	O
+base	O
+quantities	O
+and	O
+hemoglobin	B-GENE
+-	O
+oxygen	O
+affinity	O
+e	O
+.	O
+g	O
+.	O
+p50	O
+.	O
+
+100	O
+and	O
+14	O
+p	O
+.	O
+
+Here	O
+,	O
+we	O
+alter	O
+the	O
+dimerization	O
+specificity	O
+of	O
+Fos	B-GENE
+by	O
+precisely	O
+replacing	O
+its	O
+leucine	O
+zipper	O
+with	O
+that	O
+from	O
+GCN4	B-GENE
+.	O
+
+Fourth	O
+,	O
+sometime	O
+between	O
+4	O
+and	O
+24	O
+hours	O
+of	O
+recovery	O
+is	O
+necessary	O
+to	O
+reverse	O
+the	O
+effect	O
+of	O
+chronic	O
+hypoxia	O
+on	O
+cerebral	O
+blood	O
+flow	O
+.	O
+
+Kindling	O
+of	O
+the	O
+primary	O
+visual	O
+cortex	O
+(	O
+VC	O
+)	O
+was	O
+compared	O
+with	O
+that	O
+of	O
+the	O
+amygdala	O
+in	O
+cats	O
+.	O
+
+Abundant	O
+infiltration	O
+of	O
+lymphocytes	O
+and	O
+plasma	O
+cells	O
+was	O
+also	O
+wide	O
+-	O
+spread	O
+beneath	O
+the	O
+carcinoma	O
+in	O
+situ	O
+,	O
+together	O
+with	O
+the	O
+lymphoid	O
+follicles	O
+.	O
+
+These	O
+case	O
+reports	O
+provide	O
+further	O
+evidence	O
+that	O
+LiCO3	O
+can	O
+be	O
+a	O
+useful	O
+medication	O
+in	O
+the	O
+treatment	O
+of	O
+aggressive	O
+behavior	O
+and	O
+affective	O
+instability	O
+after	O
+brain	O
+injury	O
+,	O
+but	O
+that	O
+it	O
+has	O
+significant	O
+potential	O
+for	O
+neurotoxicity	O
+in	O
+this	O
+population	O
+,	O
+particularly	O
+when	O
+used	O
+in	O
+conjunction	O
+with	O
+neuroleptic	O
+agents	O
+.	O
+
+Among	O
+100	O
+cases	O
+of	O
+post	O
+-	O
+transfusion	O
+hepatitis	O
+,	O
+10	O
+are	O
+due	O
+to	O
+the	O
+hepatitis	O
+B	O
+virus	O
+(	O
+despite	O
+systematic	O
+search	O
+for	O
+HBs	B-GENE
+Ag	I-GENE
+)	O
+,	O
+89	O
+are	O
+due	O
+to	O
+one	O
+of	O
+the	O
+non	O
+-	O
+A	O
+non	O
+-	O
+B	O
+viruses	O
+(	O
+not	O
+detectable	O
+by	O
+specific	O
+serological	O
+tests	O
+)	O
+and	O
+1	O
+to	O
+several	O
+viruses	O
+,	O
+specially	O
+CMV	O
+.	O
+
+Recessive	O
+lethal	O
+mutations	O
+were	O
+isolated	O
+based	O
+upon	O
+failure	O
+to	O
+complement	O
+the	O
+recessive	O
+lethality	O
+of	O
+Df	O
+(	O
+3L	O
+)	O
+RR2	O
+,	O
+a	O
+deletion	O
+of	O
+the	O
+DRE	O
+region	O
+that	O
+removes	O
+16	O
+-	O
+18	O
+polytene	O
+chromosome	O
+bands	O
+.	O
+
+Current	O
+status	O
+and	O
+future	O
+perspectives	O
+
+K	O
+.	O
+
+A	O
+215	O
+-	O
+base	O
+-	O
+pair	O
+(	O
+bp	O
+)	O
+region	O
+of	O
+the	O
+mouse	B-GENE
+MOPC	I-GENE
+41	I-GENE
+kappa	I-GENE
+light	I-GENE
+-	I-GENE
+chain	I-GENE
+immunoglobulin	I-GENE
+gene	I-GENE
+enhancer	I-GENE
+has	O
+been	O
+analyzed	O
+for	O
+specific	O
+binding	O
+of	O
+lymphoid	O
+and	O
+nonlymphoid	O
+nuclear	O
+factors	O
+.	O
+
+Follow	O
+-	O
+up	O
+study	O
+showed	O
+85	O
+%	O
+of	O
+these	O
+patients	O
+with	O
+effectiveness	O
+.	O
+
+The	O
+other	O
+patients	O
+continued	O
+the	O
+trial	O
+with	O
+single	O
+daily	O
+doses	O
+of	O
+monotherapy	O
+.	O
+
+Neonatal	O
+Chagas	O
+disease	O
+:	O
+laboratory	O
+diagnosis	O
+during	O
+the	O
+first	O
+year	O
+of	O
+life	O
+
+Using	O
+mutated	B-GENE
+IL2R	I-GENE
+alpha	I-GENE
+promoter	I-GENE
+constructs	I-GENE
+in	O
+transient	O
+transfection	O
+and	O
+DNA	O
+binding	O
+assays	O
+,	O
+we	O
+now	O
+demonstrate	O
+that	O
+sequences	O
+located	O
+immediately	O
+upstream	O
+and	O
+downstream	O
+of	O
+the	O
+kappa	B-GENE
+B	I-GENE
+enhancer	I-GENE
+also	O
+contribute	O
+to	O
+the	O
+regulation	O
+of	O
+IL2R	B-GENE
+alpha	I-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Palindromic	O
+rheumatism	O
+
+Forty	O
+patients	O
+,	O
+divided	O
+according	O
+to	O
+their	O
+initial	O
+total	O
+gastrointestinal	O
+transit	O
+times	O
+and	O
+presenting	O
+symptoms	O
+,	O
+were	O
+treated	O
+with	O
+cimetropium	O
+bromide	O
+50	O
+mg	O
+t	O
+.	O
+d	O
+.	O
+s	O
+.	O
+or	O
+placebo	O
+for	O
+1	O
+month	O
+according	O
+to	O
+a	O
+double	O
+-	O
+blind	O
+,	O
+parallel	O
+group	O
+design	O
+.	O
+
+An	O
+immunologically	O
+related	O
+protein	O
+was	O
+detected	O
+in	O
+ribosome	O
+and	O
+membrane	O
+fractions	O
+of	O
+mitochondria	O
+from	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Mapping	O
+of	O
+RNA	O
+-	O
+temperature	B-GENE
+-	I-GENE
+sensitive	I-GENE
+mutants	I-GENE
+of	I-GENE
+Sindbis	I-GENE
+virus	I-GENE
+:	I-GENE
+complementation	I-GENE
+group	I-GENE
+F	I-GENE
+mutants	I-GENE
+have	O
+lesions	O
+in	O
+nsP4	B-GENE
+.	O
+
+The	O
+effect	O
+of	O
+the	O
+thromboxane	B-GENE
+A2	I-GENE
+(	I-GENE
+TXA2	I-GENE
+)	I-GENE
+/	I-GENE
+prostaglandin	I-GENE
+endoperoxide	I-GENE
+receptor	I-GENE
+antagonist	O
+,	O
+SQ	O
+29	O
+,	O
+548	O
+on	O
+pacing	O
+-	O
+induced	O
+ischemia	O
+was	O
+determined	O
+in	O
+anesthetized	O
+open	O
+-	O
+chest	O
+dogs	O
+.	O
+
+The	O
+recovery	O
+index	O
+(	O
+T25	O
+-	O
+T75	O
+)	O
+after	O
+the	O
+infusion	O
+stopped	O
+was	O
+similar	O
+in	O
+patients	O
+who	O
+received	O
+mivacurium	O
+and	O
+those	O
+who	O
+received	O
+suxamethonium	O
+.	O
+
+The	O
+sign	O
+of	O
+Leser	O
+-	O
+Trelat	O
+:	O
+does	O
+it	O
+exist	O
+?	O
+The	O
+sign	O
+of	O
+Leser	O
+-	O
+Trelat	O
+is	O
+usually	O
+regarded	O
+as	O
+a	O
+reliable	O
+cutaneous	O
+marker	O
+of	O
+internal	O
+malignancy	O
+.	O
+
+Three	O
+missense	O
+mutants	O
+in	O
+subunit	O
+a	O
+of	O
+the	O
+Escherichia	B-GENE
+coli	I-GENE
+F1F0	I-GENE
+-	I-GENE
+ATPase	I-GENE
+were	O
+isolated	O
+and	O
+characterized	O
+after	O
+hydroxylamine	O
+mutagenesis	O
+of	O
+a	O
+plasmid	O
+carrying	O
+the	O
+uncB	B-GENE
+(	I-GENE
+subunit	I-GENE
+a	I-GENE
+)	I-GENE
+gene	I-GENE
+.	O
+
+Moreover	O
+,	O
+exons	O
+2a	O
+and	O
+2b	O
+share	O
+the	O
+same	O
+5	O
+'	O
+sequence	O
+but	O
+differ	O
+from	O
+each	O
+other	O
+by	O
+the	O
+use	O
+of	O
+two	O
+distinct	O
+donor	O
+splice	O
+sites	O
+171	O
+bp	O
+apart	O
+in	O
+the	O
+gene	O
+.	O
+
+S1	B-GENE
+nuclease	I-GENE
+analysis	O
+of	O
+RNA	O
+prepared	O
+after	O
+transfection	O
+of	O
+these	O
+HIV	O
+constructs	O
+into	O
+HeLa	O
+cells	O
+infected	O
+with	O
+wild	O
+-	O
+type	O
+adenovirus	O
+indicated	O
+that	O
+the	O
+enhancer	O
+,	O
+SP1	B-GENE
+,	O
+TATA	O
+,	O
+and	O
+a	O
+portion	O
+of	O
+the	O
+transactivation	O
+-	O
+responsive	O
+element	O
+were	O
+each	O
+required	O
+for	O
+complete	O
+E1A	B-GENE
+/	O
+E1B	B-GENE
+-	O
+mediated	O
+activation	O
+of	O
+the	O
+HIV	B-GENE
+LTR	I-GENE
+.	O
+
+In	O
+supine	O
+position	O
+,	O
+plasma	O
+ANP	B-GENE
+levels	O
+ranged	O
+from	O
+12	O
+pg	O
+/	O
+ml	O
+to	O
+51	O
+.	O
+5	O
+pg	O
+/	O
+ml	O
+,	O
+with	O
+an	O
+average	O
+level	O
+of	O
+35	O
+.	O
+3	O
++	O
+/	O
+-	O
+11	O
+.	O
+5	O
+pg	O
+/	O
+ml	O
+.	O
+
+The	O
+overall	O
+prevalence	O
+of	O
+HBV	O
+markers	O
+was	O
+higher	O
+among	O
+staff	O
+members	O
+than	O
+in	O
+the	O
+blood	O
+donors	O
+of	O
+our	O
+area	O
+.	O
+
+Quantitative	O
+predictions	O
+are	O
+confirmed	O
+for	O
+the	O
+positive	O
+responses	O
+,	O
+but	O
+not	O
+for	O
+the	O
+negatives	O
+,	O
+suggesting	O
+that	O
+the	O
+SSTS	O
+model	O
+is	O
+incorrect	O
+.	O
+
+Plasma	O
+concentrations	O
+of	O
+ANF	B-GENE
+(	O
+pANF	B-GENE
+)	O
+,	O
+aldosterone	O
+(	O
+PAC	O
+)	O
+and	O
+renin	B-GENE
+(	O
+PRC	B-GENE
+)	O
+were	O
+measured	O
+daily	O
+,	O
+as	O
+were	O
+hemodynamic	O
+parameters	O
+.	O
+
+The	O
+adenovirus	B-GENE
+E1A	I-GENE
+gene	I-GENE
+encodes	O
+a	O
+protein	O
+that	O
+transcriptionally	O
+activates	O
+viral	B-GENE
+early	I-GENE
+genes	I-GENE
+.	O
+
+Administration	O
+of	O
+dexamethasone	O
+was	O
+associated	O
+with	O
+progressive	O
+rises	O
+in	O
+plasma	O
+17	O
+alpha	O
+OH	O
+progesterone	O
+,	O
+11	O
+beta	O
+-	O
+desoxycortisol	O
+,	O
+DHEA	O
+sulphate	O
+,	O
+androstenedione	O
+and	O
+testosterone	O
+,	O
+together	O
+with	O
+increased	O
+urinary	O
+excretion	O
+of	O
+androsterone	O
+,	O
+11	O
+beta	O
+OH	O
+androsterone	O
+,	O
+etiocholanolone	O
+,	O
+DHEA	O
+,	O
+and	O
+16	O
+alpha	O
+OH	O
+DHEA	O
+.	O
+
+RNA	O
+transcripts	O
+that	O
+hybridize	O
+to	O
+the	O
+introduced	O
+foreign	O
+gene	O
+have	O
+been	O
+identified	O
+.	O
+
+In	O
+HeLa	O
+cells	O
+,	O
+it	O
+activated	O
+transcription	O
+from	O
+the	O
+herpes	B-GENE
+simplex	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+thymidine	I-GENE
+kinase	I-GENE
+promoter	I-GENE
+linked	O
+to	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+gene	I-GENE
+when	O
+located	O
+in	O
+inverted	O
+orientation	O
+upstream	O
+of	O
+the	O
+thymidine	B-GENE
+kinase	I-GENE
+promoter	I-GENE
+or	O
+downstream	O
+of	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+gene	I-GENE
+coding	I-GENE
+sequence	I-GENE
+.	O
+
+At	O
+the	O
+basal	O
+unstimulated	O
+condition	O
+,	O
+Ren1d	B-GENE
+5	I-GENE
+'	I-GENE
+flanking	I-GENE
+sequence	I-GENE
+in	O
+the	O
+sense	O
+orientation	O
+inhibited	O
+basal	O
+CAT	B-GENE
+expression	O
+from	O
+the	O
+TK	B-GENE
+promoter	I-GENE
+of	O
+pUTKAT1	O
+,	O
+whereas	O
+the	O
+same	O
+sequence	O
+in	O
+the	O
+antisense	O
+orientation	O
+did	O
+not	O
+.	O
+
+None	O
+were	O
+restricted	O
+from	O
+clinical	O
+duties	O
+,	O
+were	O
+given	O
+varicella	B-GENE
+-	I-GENE
+zoster	I-GENE
+immune	I-GENE
+globulin	I-GENE
+,	O
+or	O
+developed	O
+disease	O
+.	O
+
+In	O
+the	O
+formalin	O
+test	O
+,	O
+however	O
+,	O
+naloxone	O
+attenuated	O
+morphine	O
+analgesia	O
+at	O
+the	O
+lower	O
+doses	O
+(	O
+0	O
+.	O
+1	O
+and	O
+0	O
+.	O
+3	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+potentiated	O
+morphine	O
+analgesia	O
+at	O
+the	O
+highest	O
+dose	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+We	O
+have	O
+isolated	O
+cDNA	O
+clones	O
+from	O
+rat	O
+brain	O
+and	O
+human	O
+liver	O
+encoding	O
+a	O
+putative	O
+isoform	O
+of	O
+the	O
+Na	B-GENE
+,	I-GENE
+K	I-GENE
+-	I-GENE
+ATPase	I-GENE
+beta	I-GENE
+subunit	I-GENE
+.	O
+
+We	O
+have	O
+determined	O
+that	O
+several	O
+E1	B-GENE
+mutants	I-GENE
+mapping	O
+in	O
+both	O
+the	O
+M	O
+and	O
+R	O
+regions	O
+and	O
+a	O
+single	O
+mutant	O
+of	O
+the	O
+upstream	O
+regulatory	O
+region	O
+have	O
+a	O
+higher	O
+transforming	O
+activity	O
+on	O
+mouse	O
+C127	O
+cells	O
+than	O
+the	O
+wild	O
+-	O
+type	O
+genome	O
+does	O
+.	O
+
+UbiA	B-GENE
+is	O
+also	O
+unique	O
+among	O
+known	O
+polyubiquitin	B-GENE
+genes	I-GENE
+in	O
+containing	O
+four	O
+cis	O
+-	O
+spliced	O
+introns	O
+within	O
+its	O
+coding	O
+sequence	O
+.	O
+
+That	O
+of	O
+the	O
+T2	B-GENE
+gene	I-GENE
+contains	O
+numerous	O
+potential	O
+sites	O
+for	O
+binding	O
+the	O
+mammalian	B-GENE
+transcription	I-GENE
+factor	I-GENE
+SP1	I-GENE
+,	O
+but	O
+no	O
+TATA	O
+or	O
+CCAAT	O
+sequences	O
+are	O
+evident	O
+near	O
+to	O
+its	O
+5	O
+'	O
+end	O
+,	O
+although	O
+these	O
+latter	O
+features	O
+are	O
+associated	O
+with	O
+the	O
+human	B-GENE
+T1	I-GENE
+gene	I-GENE
+.	O
+
+Radiation	O
+therapy	O
+was	O
+effective	O
+in	O
+controlling	O
+symptomatic	O
+metastasis	O
+in	O
+all	O
+three	O
+patients	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+patients	O
+who	O
+undergo	O
+postoperative	O
+irradiation	O
+for	O
+low	O
+grade	O
+spinal	O
+astrocytomas	O
+and	O
+localized	O
+spinal	O
+ependymomas	O
+achieve	O
+excellent	O
+survival	O
+.	O
+
+The	O
+methylation	O
+of	O
+nuclear	O
+and	O
+chloroplast	O
+DNAs	O
+has	O
+been	O
+examined	O
+in	O
+relation	O
+to	O
+the	O
+known	O
+differential	O
+expression	O
+of	O
+C4	B-GENE
+photosynthesis	I-GENE
+genes	I-GENE
+in	O
+the	O
+bundle	O
+sheath	O
+and	O
+mesophyll	O
+cells	O
+of	O
+etiolated	O
+,	O
+greening	O
+,	O
+and	O
+fully	O
+green	O
+maize	O
+leaves	O
+.	O
+
+S1	B-GENE
+nuclease	I-GENE
+analysis	O
+of	O
+RNA	O
+from	O
+chemically	O
+induced	O
+B95	O
+-	O
+8	O
+cells	O
+and	O
+from	O
+Vero	O
+cells	O
+cotransfected	O
+with	O
+NotI	B-GENE
+repeat	I-GENE
+promoter	I-GENE
+-	O
+CAT	B-GENE
+and	O
+Z	B-GENE
+showed	O
+that	O
+Z	B-GENE
+transactivation	O
+increased	O
+the	O
+level	O
+of	O
+correctly	O
+initiated	O
+,	O
+stable	O
+RNA	O
+transcripts	O
+.	O
+
+Analysis	O
+of	O
+the	O
+DNA	O
+from	O
+15	O
+cases	O
+of	O
+sporadic	O
+and	O
+familial	O
+Wilms	O
+'	O
+tumor	O
+did	O
+not	O
+reveal	O
+any	O
+changes	O
+,	O
+indicating	O
+that	O
+the	O
+translocation	O
+breakpoint	O
+does	O
+not	O
+reside	O
+in	O
+this	O
+gene	O
+.	O
+
+We	O
+also	O
+provide	O
+evidence	O
+that	O
+neither	O
+the	O
+lambda	B-GENE
+O	I-GENE
+and	O
+P	B-GENE
+initiators	I-GENE
+nor	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+DnaJ	I-GENE
+and	O
+DnaK	B-GENE
+heat	O
+shock	O
+proteins	O
+play	O
+a	O
+direct	O
+role	O
+in	O
+the	O
+propagation	O
+of	O
+lambda	O
+replication	O
+forks	O
+in	O
+vitro	O
+.	O
+
+Synthetic	O
+oligonucleotides	O
+representing	O
+the	O
+19	O
+bp	O
+repeat	O
+unit	O
+strongly	O
+reduced	O
+the	O
+activity	O
+of	O
+the	O
+IE1	B-GENE
+/	I-GENE
+2	I-GENE
+enhancer	I-GENE
+/	I-GENE
+promoter	I-GENE
+in	O
+cotransfection	O
+assays	O
+after	O
+transient	O
+expression	O
+.	O
+
+Effects	O
+of	O
+nitrogen	O
+(	O
+PN2	O
+:	O
+5	O
+and	O
+14	O
+MPa	O
+)	O
+and	O
+helium	O
+(	O
+PHe	O
+:	O
+13	O
+and	O
+14	O
+MPa	O
+)	O
+were	O
+also	O
+tested	O
+.	O
+
+The	O
+mustard	B-GENE
+chloroplast	I-GENE
+gene	I-GENE
+rps16	I-GENE
+is	O
+split	O
+by	O
+an	O
+887	O
+bp	O
+group	O
+II	O
+(	O
+or	O
+III	O
+)	O
+intron	O
+.	O
+
+Antibodies	O
+raised	O
+to	O
+the	O
+expressed	O
+NS3	B-GENE
+by	O
+immunization	O
+of	O
+mice	O
+detected	O
+both	O
+NS3	B-GENE
+and	O
+NS3A	B-GENE
+in	O
+BTV	O
+-	O
+10	O
+-	O
+infected	O
+BHK	O
+cells	O
+but	O
+not	O
+in	O
+purified	O
+BTV	O
+-	O
+10	O
+virus	O
+particles	O
+.	O
+
+Similarly	O
+,	O
+supraventricular	O
+tachycaydia	O
+following	O
+resuscitative	O
+efforts	O
+appeared	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+negative	O
+outcome	O
+.	O
+
+The	O
+negative	O
+calcium	O
+balance	O
+with	O
+hyperparathyroidemia	O
+occurred	O
+after	O
+continuous	O
+oral	O
+administration	O
+of	O
+Cd	O
+and	O
+developed	O
+via	O
+increased	O
+urinary	O
+excretion	O
+of	O
+calcium	O
+.	O
+
+Clone	O
+4c	O
+(	O
+2681	O
+bp	O
+)	O
+had	O
+a	O
+coding	O
+region	O
+identical	O
+to	O
+that	O
+of	O
+clone	O
+22c	O
+but	O
+it	O
+included	O
+a	O
+putative	O
+intron	O
+of	O
+959	O
+bp	O
+.	O
+
+The	O
+application	O
+of	O
+ISH	O
+and	O
+IHC	O
+did	O
+not	O
+change	O
+significantly	O
+the	O
+routine	O
+histologic	O
+classification	O
+of	O
+pneumonias	O
+into	O
+CMV	O
+-	O
+IP	O
+and	O
+IIP	O
+.	O
+
+Validity	O
+of	O
+immunohistology	O
+and	O
+in	O
+situ	O
+hybridization	O
+in	O
+the	O
+differential	O
+diagnosis	O
+of	O
+cytomegalovirus	O
+pneumonia	O
+and	O
+idiopathic	O
+interstitial	O
+pneumonia	O
+after	O
+allogenic	O
+bone	O
+marrow	O
+transplantation	O
+
+The	O
+unique	O
+nature	O
+and	O
+arrangement	O
+of	O
+the	O
+ANT1	B-GENE
+transcriptional	I-GENE
+control	I-GENE
+elements	I-GENE
+may	O
+account	O
+for	O
+this	O
+differential	O
+expression	O
+.	O
+
+The	O
+Bacillus	B-GENE
+subtilis	I-GENE
+phage	I-GENE
+phi	I-GENE
+105	I-GENE
+repressor	I-GENE
+,	O
+a	O
+lambda	B-GENE
+repressor	I-GENE
+-	O
+like	O
+transcriptional	O
+regulatory	O
+protein	O
+,	O
+was	O
+overproduced	O
+in	O
+Escherichia	O
+coli	O
+and	O
+purified	O
+to	O
+near	O
+homogeneity	O
+in	O
+order	O
+to	O
+examine	O
+its	O
+in	O
+vitro	O
+DNA	O
+-	O
+binding	O
+properties	O
+.	O
+
+In	O
+consequence	O
+,	O
+the	O
+gpI	B-GENE
+derived	O
+from	O
+cells	O
+infected	O
+with	O
+mO74	O
+showed	O
+antigenic	O
+characteristics	O
+similar	O
+to	O
+those	O
+of	O
+gpI	B-GENE
+from	O
+VZV	O
+-	O
+infected	O
+cells	O
+as	O
+determined	O
+from	O
+the	O
+immunoprecipitation	O
+pattern	O
+,	O
+although	O
+the	O
+molecular	O
+weight	O
+of	O
+each	O
+polypeptide	O
+was	O
+different	O
+,	O
+and	O
+antibody	O
+produced	O
+in	O
+rabbits	O
+infected	O
+with	O
+recombinant	O
+virus	O
+had	O
+a	O
+high	O
+neutralizing	O
+activity	O
+,	O
+when	O
+the	O
+reaction	O
+was	O
+performed	O
+with	O
+complement	O
+.	O
+
+However	O
+,	O
+bilateral	O
+diffuse	O
+pulmonary	O
+infiltrations	O
+developed	O
+21	O
+days	O
+later	O
+.	O
+
+Grossly	O
+,	O
+the	O
+incidence	O
+of	O
+a	O
+type	O
+IIc	O
+carcinoma	O
+was	O
+46	O
+.	O
+5	O
+%	O
+and	O
+that	O
+of	O
+a	O
+IIc	O
++	O
+III	O
+type	O
+was	O
+20	O
+.	O
+5	O
+%	O
+,	O
+respectively	O
+.	O
+
+VP5	B-GENE
+,	O
+which	O
+encodes	O
+the	O
+major	B-GENE
+capsid	I-GENE
+protein	I-GENE
+,	O
+each	O
+fused	O
+to	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+gene	I-GENE
+.	O
+
+Of	O
+202	O
+initially	O
+seronegative	O
+caretakers	O
+(	O
+observed	O
+for	O
+an	O
+average	O
+of	O
+305	O
+days	O
+per	O
+woman	O
+)	O
+,	O
+19	O
+seroconverted	O
+,	O
+for	O
+an	O
+annual	O
+seroconversion	O
+rate	O
+of	O
+11	O
+percent	O
+.	O
+
+First	O
+,	O
+a	O
+pet54	B-GENE
+:	O
+:	O
+LEU2	B-GENE
+cytoductant	O
+bearing	O
+the	O
+'	O
+short	O
+'	O
+mitochondrial	O
+genome	O
+that	O
+lacks	O
+both	O
+COX1	B-GENE
+introns	I-GENE
+aI5	B-GENE
+alpha	I-GENE
+and	O
+aI5	B-GENE
+beta	I-GENE
+is	O
+defective	O
+only	O
+in	O
+COX3	B-GENE
+gene	I-GENE
+expression	O
+and	O
+not	O
+in	O
+COX1	B-GENE
+mRNA	I-GENE
+splicing	O
+or	O
+mRNA	O
+translation	O
+.	O
+
+Insert2	O
+contains	O
+repetitive	O
+non	O
+-	O
+Ig	B-GENE
+-	O
+related	O
+sequences	O
+and	O
+a	O
+small	B-GENE
+Ig	I-GENE
+-	I-GENE
+related	I-GENE
+sequence	I-GENE
+.	O
+
+Since	O
+considerable	O
+variations	O
+in	O
+length	O
+and	O
+primary	O
+sequence	O
+in	O
+the	O
+CDR3	B-GENE
+(	O
+complementarity	B-GENE
+determining	I-GENE
+region	I-GENE
+)	O
+peptides	O
+of	O
+all	O
+the	O
+H	B-GENE
+-	I-GENE
+chains	I-GENE
+are	O
+evident	O
+,	O
+conservation	O
+of	O
+the	O
+D	B-GENE
+-	I-GENE
+region	I-GENE
+structure	O
+does	O
+not	O
+appear	O
+to	O
+be	O
+necessary	O
+for	O
+effective	O
+hapten	O
+binding	O
+.	O
+
+Tyrosine	B-GENE
+kinase	I-GENE
+oncogenes	O
+abrogate	O
+interleukin	B-GENE
+-	I-GENE
+3	I-GENE
+dependence	O
+of	O
+murine	O
+myeloid	O
+cells	O
+through	O
+signaling	O
+pathways	O
+involving	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+:	O
+conditional	O
+regulation	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+transcription	O
+by	O
+temperature	O
+-	O
+sensitive	O
+v	B-GENE
+-	I-GENE
+abl	I-GENE
+.	O
+
+The	O
+DNA	O
+helix	O
+at	O
+the	O
+tandemly	O
+repeated	O
+,	O
+13mer	O
+sequence	O
+is	O
+thermodynamically	O
+unstable	O
+,	O
+as	O
+evidenced	O
+by	O
+hypersensitivity	O
+to	O
+single	B-GENE
+-	I-GENE
+strand	I-GENE
+-	I-GENE
+specific	I-GENE
+nuclease	I-GENE
+in	O
+a	O
+negatively	O
+supercoiled	O
+plasmid	O
+,	O
+and	O
+demonstrated	O
+by	O
+stable	O
+DNA	O
+unwinding	O
+seen	O
+after	O
+two	O
+-	O
+dimensional	O
+gel	O
+electrophoresis	O
+of	O
+topoisomers	O
+.	O
+
+There	O
+has	O
+been	O
+similar	O
+improvement	O
+in	O
+treating	O
+ampullary	O
+and	O
+periampullary	O
+cancer	O
+,	O
+gallbladder	O
+cancer	O
+,	O
+or	O
+extrahepatic	O
+bile	O
+duct	O
+cancer	O
+.	O
+
+Beta	B-GENE
+-	I-GENE
+endorphin	I-GENE
+,	O
+ACTH	B-GENE
+and	O
+cortisol	O
+secretion	O
+were	O
+measured	O
+in	O
+twelve	O
+healthy	O
+adult	O
+males	O
+after	O
+nasal	O
+spray	O
+administration	O
+200	O
+IU	O
+salmon	B-GENE
+calcitonin	I-GENE
+.	O
+
+The	O
+data	O
+indicate	O
+that	O
+calcitonin	B-GENE
+induced	O
+a	O
+beta	B-GENE
+-	I-GENE
+endorphin	I-GENE
+increase	O
+independent	O
+of	O
+enhanced	O
+corticotrophin	B-GENE
+-	O
+cortisol	O
+release	O
+.	O
+
+Other	O
+hemostatic	O
+values	O
+evaluated	O
+were	O
+activated	O
+partial	O
+thromboplastin	B-GENE
+times	O
+,	O
+prothrombin	B-GENE
+times	O
+,	O
+thrombin	B-GENE
+times	O
+,	O
+fibrinogen	B-GENE
+,	O
+platelet	O
+counts	O
+,	O
+and	O
+fibrin	B-GENE
+/	O
+fibrinogen	B-GENE
+degradation	O
+products	O
+.	O
+
+Rare	O
+neurogenic	O
+tumor	O
+with	O
+metastasis	O
+to	O
+mouth	O
+,	O
+jaw	O
+and	O
+face	O
+regions	O
+
+We	O
+have	O
+designated	O
+the	O
+protein	O
+"	B-GENE
+cellular	I-GENE
+NBP	I-GENE
+"	I-GENE
+(	O
+CNBP	B-GENE
+)	O
+.	O
+
+Responsiveness	O
+to	O
+beta	O
+-	O
+2	O
+agonist	O
+therapy	O
+was	O
+retained	O
+with	O
+both	O
+agents	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Drug	O
+use	O
+in	O
+trauma	O
+victims	O
+.	O
+
+A	O
+critical	O
+heart	O
+rate	O
+and	O
+/	O
+or	O
+appropriate	O
+sympathetic	O
+state	O
+was	O
+found	O
+to	O
+provoke	O
+all	O
+instances	O
+of	O
+reentrant	O
+or	O
+automatic	O
+atrial	O
+tachycardia	O
+and	O
+atypical	O
+junctional	O
+tachycardia	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+neu	B-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+did	O
+not	O
+show	O
+kinase	O
+activity	O
+or	O
+transforming	O
+properties	O
+when	O
+expressed	O
+at	O
+similar	O
+levels	O
+in	O
+NIH	O
+3T3	O
+cells	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+The	O
+65	O
+-	O
+bp	O
+sequence	O
+contains	O
+the	O
+octameric	O
+cAMP	O
+-	O
+responsive	O
+enhancer	O
+(	O
+CRE	O
+)	O
+TGACGTCA	O
+(	O
+nucleotides	O
+-	O
+48	O
+to	O
+-	O
+41	O
+)	O
+.	O
+
+Somatostatin	B-GENE
+gene	I-GENE
+expression	O
+in	O
+pancreatic	O
+islet	O
+cells	O
+is	O
+directed	O
+by	O
+cell	O
+-	O
+specific	O
+DNA	O
+control	O
+elements	O
+and	O
+DNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+full	O
+mu	O
+-	O
+opioid	O
+agonists	O
+fentanyl	O
+,	O
+morphine	O
+,	O
+I	O
+-	O
+methadone	O
+and	O
+levorphanol	O
+produced	O
+50	O
+%	O
+fentanyl	O
+-	O
+appropriate	O
+responding	O
+at	O
+doses	O
+only	O
+1	O
+.	O
+3	O
+to	O
+10	O
+.	O
+9	O
+times	O
+smaller	O
+than	O
+those	O
+required	O
+to	O
+decrease	O
+response	O
+rates	O
+by	O
+50	O
+%	O
+.	O
+
+After	O
+overtraining	O
+on	O
+the	O
+original	O
+discrimination	O
+,	O
+the	O
+controls	O
+showed	O
+the	O
+normal	O
+difficulty	O
+in	O
+learning	O
+the	O
+first	O
+reversal	O
+.	O
+
+Isolation	O
+and	O
+characterization	O
+of	O
+a	O
+cDNA	O
+encoding	O
+a	O
+putative	O
+cytokine	O
+which	O
+is	O
+induced	O
+by	O
+stimulation	O
+via	O
+the	O
+CD2	B-GENE
+structure	I-GENE
+on	O
+human	O
+T	O
+lymphocytes	O
+.	O
+
+After	O
+termination	O
+of	O
+medication	O
+the	O
+animals	O
+were	O
+kindled	O
+electrically	O
+in	O
+the	O
+nucleus	O
+amygdala	O
+.	O
+
+Haploid	O
+cells	O
+of	O
+mating	O
+type	O
+A	O
+of	O
+the	O
+basidiomycetous	O
+yeast	O
+Rhodosporidium	O
+toruloides	O
+secrete	O
+a	O
+mating	O
+pheromone	O
+,	O
+rhodotorucine	B-GENE
+A	I-GENE
+,	O
+which	O
+is	O
+an	O
+undecapeptide	O
+containing	O
+S	O
+-	O
+farnesyl	O
+cysteine	O
+at	O
+its	O
+carboxy	O
+terminus	O
+.	O
+
+Tumour	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+and	O
+adult	O
+respiratory	O
+distress	O
+syndrome	O
+.	O
+
+Monitoring	O
+of	O
+rheumatoid	O
+arthritis	O
+.	O
+
+The	O
+decrease	O
+in	O
+left	O
+ventricular	O
+(	O
+LV	O
+)	O
+stroke	O
+volume	O
+during	O
+positive	O
+end	O
+-	O
+expiratory	O
+pressure	O
+(	O
+PEEP	O
+)	O
+has	O
+been	O
+attributed	O
+to	O
+reduced	O
+LV	O
+filling	O
+and	O
+a	O
+decreased	O
+contractile	O
+state	O
+.	O
+
+An	O
+experiment	O
+on	O
+the	O
+return	O
+-	O
+of	O
+-	O
+fear	O
+(	O
+ROF	O
+)	O
+was	O
+carried	O
+out	O
+on	O
+40	O
+snake	O
+-	O
+or	O
+spider	O
+-	O
+phobic	O
+subjects	O
+in	O
+order	O
+to	O
+determine	O
+whether	O
+an	O
+arousing	O
+event	O
+that	O
+occurs	O
+shortly	O
+before	O
+retest	O
+influences	O
+the	O
+magnitude	O
+of	O
+the	O
+ROF	O
+.	O
+
+Evolutionary	O
+conservation	O
+of	O
+homeodomain	B-GENE
+-	O
+binding	O
+sites	O
+and	O
+other	O
+sequences	O
+upstream	O
+and	O
+within	O
+the	O
+major	O
+transcription	O
+unit	O
+of	O
+the	O
+Drosophila	B-GENE
+segmentation	I-GENE
+gene	I-GENE
+engrailed	I-GENE
+.	O
+
+To	O
+assess	O
+the	O
+functional	O
+importance	O
+of	O
+these	O
+NBS	O
+in	O
+the	O
+overall	O
+drug	O
+resistance	O
+phenotype	O
+conferred	O
+by	O
+mdr1	B-GENE
+,	O
+we	O
+introduced	O
+amino	O
+acid	O
+substitutions	O
+in	O
+the	O
+core	O
+consensus	O
+sequence	O
+for	O
+nucleotide	O
+binding	O
+,	O
+GXGKST	O
+.	O
+
+When	O
+the	O
+first	O
+twitch	O
+of	O
+TOF	O
+spontaneously	O
+recovered	O
+to	O
+10	O
+%	O
+of	O
+control	O
+value	O
+,	O
+neostigmine	O
+was	O
+injected	O
+(	O
+40	O
+micrograms	O
+/	O
+kg	O
+in	O
+adults	O
+,	O
+30	O
+micrograms	O
+/	O
+kg	O
+in	O
+infants	O
+and	O
+children	O
+)	O
+.	O
+
+No	O
+significant	O
+differences	O
+were	O
+found	O
+in	O
+relation	O
+to	O
+Type	O
+A	O
+behaviour	O
+and	O
+beta	B-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+blockade	O
+.	O
+
+Selection	O
+of	O
+the	O
+22	O
+items	O
+of	O
+the	O
+Clinical	O
+Institute	O
+Withdrawal	O
+Assessment	O
+-	O
+Benzodiazepines	O
+(	O
+CIWA	O
+-	O
+B	O
+)	O
+was	O
+based	O
+on	O
+statistically	O
+significant	O
+differences	O
+between	O
+baseline	O
+and	O
+critical	O
+withdrawal	O
+periods	O
+in	O
+high	O
+-	O
+dose	O
+subjects	O
+and	O
+between	O
+symptoms	O
+associated	O
+with	O
+placebo	O
+and	O
+diazepam	O
+in	O
+low	O
+-	O
+dose	O
+subjects	O
+,	O
+using	O
+contingency	O
+tables	O
+and	O
+logistic	O
+regression	O
+analysis	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+revealed	O
+multiple	O
+oIGF	B-GENE
+-	I-GENE
+I	I-GENE
+transcripts	I-GENE
+in	O
+a	O
+broad	O
+band	O
+at	O
+800	O
+-	O
+1	O
+,	O
+100	O
+nucleotides	O
+and	O
+other	O
+transcripts	O
+of	O
+higher	O
+molecular	O
+weight	O
+in	O
+liver	O
+.	O
+
+Materials	O
+science	O
+studies	O
+on	O
+the	O
+soldering	O
+of	O
+different	O
+orthodontic	O
+wires	O
+
+The	O
+latency	O
+time	O
+for	O
+the	O
+lactate	O
+concentration	O
+to	O
+reach	O
+the	O
+top	O
+values	O
+was	O
+reduced	O
+by	O
+aerobic	O
+training	O
+(	O
+T2	O
+)	O
+.	O
+
+In	O
+patients	O
+resistant	O
+to	O
+VAD	O
+,	O
+high	O
+-	O
+dose	O
+therapies	O
+with	O
+intravenous	O
+melphalan	O
+,	O
+a	O
+CBV	O
+combination	O
+(	O
+cyclophosphamide	O
+-	O
+BCNU	O
+-	O
+VP	O
+-	O
+16	O
+)	O
+or	O
+an	O
+EDAP	O
+regimen	O
+(	O
+VP	O
+-	O
+16	O
+-	O
+platinum	O
+)	O
+produced	O
+responses	O
+in	O
+about	O
+40	O
+%	O
+of	O
+patients	O
+.	O
+
+The	O
+avian	O
+cellular	O
+homolog	O
+of	O
+the	O
+oncogene	B-GENE
+jun	I-GENE
+.	O
+
+High	O
+ATP	O
+/	O
+GTP	O
+ratios	O
+promoted	O
+initiation	O
+of	O
+RNA	O
+primer	O
+synthesis	O
+at	O
+3	O
+'	O
+-	O
+dCTTT	O
+sites	O
+,	O
+whereas	O
+low	O
+ATP	O
+/	O
+GTP	O
+ratios	O
+promoted	O
+initiation	O
+at	O
+3	O
+'	O
+-	O
+dCCC	O
+sites	O
+.	O
+
+After	O
+hepatitis	O
+B	O
+vaccine	O
+immunization	O
+,	O
+serum	O
+antibody	O
+response	O
+was	O
+of	O
+primary	O
+type	O
+in	O
+33	O
+cases	O
+with	O
+anti	B-GENE
+-	I-GENE
+HBs	I-GENE
+less	O
+than	O
+2	O
+.	O
+1	O
+S	O
+/	O
+N	O
+(	O
+S	O
+/	O
+N	O
+Ratio	O
+Unit	O
+)	O
+at	O
+T0	O
+,	O
+the	O
+anti	B-GENE
+-	I-GENE
+HBs	I-GENE
+positive	O
+rate	O
+was	O
+39	O
+.	O
+4	O
+%	O
+,	O
+84	O
+.	O
+8	O
+%	O
+,	O
+96	O
+.	O
+7	O
+%	O
+and	O
+96	O
+.	O
+7	O
+%	O
+in	O
+T1	O
+,	O
+T2	O
+,	O
+T0	O
+and	O
+T12	O
+respectively	O
+.	O
+
+The	O
+experimental	O
+design	O
+incorporated	O
+a	O
+multiple	O
+regression	O
+model	O
+,	O
+sequential	O
+treatments	O
+and	O
+a	O
+proportional	O
+end	O
+point	O
+(	O
+95	O
+%	O
+)	O
+for	O
+protection	O
+time	O
+.	O
+
+Interspecific	O
+complementation	O
+tests	O
+showed	O
+that	O
+the	O
+P7	B-GENE
+proteins	I-GENE
+are	O
+unable	O
+to	O
+complement	O
+P1	B-GENE
+parA	B-GENE
+or	O
+parB	B-GENE
+mutants	I-GENE
+,	O
+and	O
+the	O
+P1	B-GENE
+proteins	I-GENE
+fail	O
+to	O
+complement	O
+the	O
+P7	B-GENE
+mutations	I-GENE
+.	O
+
+GN101	O
+,	O
+YC819	O
+-	O
+9	O
+,	O
+and	O
+SB3	O
+.	O
+
+Analysis	O
+of	O
+the	O
+inferred	O
+1	B-GENE
+,	I-GENE
+859	I-GENE
+-	I-GENE
+residue	I-GENE
+ama	I-GENE
+-	I-GENE
+1	I-GENE
+product	I-GENE
+showed	O
+considerable	O
+identity	O
+with	O
+the	O
+largest	O
+subunit	O
+of	O
+RNAP	B-GENE
+II	I-GENE
+from	O
+other	O
+organisms	O
+,	O
+including	O
+the	O
+presence	O
+of	O
+a	O
+zinc	O
+finger	O
+motif	O
+near	O
+the	O
+amino	O
+terminus	O
+,	O
+and	O
+a	O
+carboxyl	O
+-	O
+terminal	O
+domain	O
+of	O
+42	O
+tandemly	O
+reiterated	O
+heptamers	O
+with	O
+the	O
+consensus	O
+Tyr	O
+Ser	O
+Pro	O
+Thr	O
+Ser	O
+Pro	O
+Ser	O
+.	O
+
+5	O
+.	O
+
+None	O
+of	O
+the	O
+measured	O
+parameters	O
+(	O
+heart	O
+contents	O
+of	O
+neutral	O
+lipids	O
+,	O
+total	O
+phospholipids	O
+,	O
+phosphatidylcholine	O
+,	O
+phosphatidylethanolamine	O
+,	O
+diphosphatidylglycerol	O
+,	O
+sphingomyelin	O
+and	O
+fatty	O
+acid	O
+composition	O
+of	O
+each	O
+phospholipid	O
+class	O
+)	O
+appeared	O
+to	O
+be	O
+related	O
+with	O
+the	O
+grading	O
+of	O
+the	O
+lesions	O
+.	O
+
+Of	O
+165	O
+women	O
+with	O
+non	O
+-	O
+malignant	O
+diagnoses	O
+26	O
+(	O
+16	O
+%	O
+)	O
+had	O
+CA	B-GENE
+125	I-GENE
+levels	O
+in	O
+excess	O
+of	O
+35	O
+U	O
+/	O
+ml	O
+and	O
+8	O
+(	O
+5	O
+%	O
+)	O
+greater	O
+than	O
+65	O
+U	O
+/	O
+ml	O
+.	O
+
+We	O
+conclude	O
+that	O
+at	O
+steady	O
+state	O
+the	O
+timing	O
+of	O
+a	O
+light	O
+meal	O
+is	O
+unlikely	O
+to	O
+alter	O
+in	O
+any	O
+clinically	O
+important	O
+manner	O
+the	O
+pharmacokinetics	O
+of	O
+nifedipine	O
+released	O
+from	O
+'	O
+biphasic	O
+'	O
+tablets	O
+.	O
+
+The	O
+GALT	O
+-	O
+primed	O
+calves	O
+had	O
+increased	O
+serum	O
+IgG	B-GENE
+,	O
+lavage	O
+IgG	B-GENE
+and	O
+IgA	B-GENE
+and	O
+increased	O
+LNA	B-GENE
+titers	O
+in	O
+both	O
+lavage	O
+fluids	O
+and	O
+serum	O
+following	O
+the	O
+SC	O
+dose	O
+of	O
+killed	O
+bacteria	O
+.	O
+
+Recent	O
+investigations	O
+have	O
+shown	O
+that	O
+Grenz	O
+rays	O
+can	O
+suppress	O
+the	O
+allergic	O
+contact	O
+dermatitis	O
+reaction	O
+completely	O
+and	O
+that	O
+Langerhans	O
+cells	O
+,	O
+identified	O
+by	O
+OKT6	B-GENE
+antibodies	I-GENE
+and	O
+electron	O
+microscopy	O
+,	O
+disappear	O
+from	O
+the	O
+epidermis	O
+at	O
+the	O
+same	O
+time	O
+.	O
+
+The	O
+elements	O
+responsible	O
+for	O
+glucocorticoid	O
+stimulation	O
+of	O
+ADH	B-GENE
+gene	I-GENE
+transcription	O
+appear	O
+to	O
+reside	O
+outside	O
+of	O
+this	O
+region	O
+.	O
+
+1	O
+.	O
+
+The	O
+present	O
+studies	O
+compare	O
+the	O
+biochemical	O
+characteristics	O
+,	O
+Kanagawa	O
+hemolysin	B-GENE
+reactions	O
+,	O
+and	O
+plasmid	O
+profiles	O
+of	O
+13	O
+patient	O
+and	O
+221	O
+environmental	O
+isolates	O
+of	O
+the	O
+organism	O
+.	O
+
+High	O
+values	O
+of	O
+both	O
+retinol	O
+and	O
+beta	O
+-	O
+carotene	O
+were	O
+found	O
+in	O
+full	O
+fat	O
+cheeses	O
+and	O
+whipping	O
+cream	O
+:	O
+from	O
+179	O
+.	O
+0	O
+(	O
+cheese	O
+,	O
+Edam	O
+-	O
+type	O
+)	O
+to	O
+318	O
+.	O
+7	O
+micrograms	O
+/	O
+100	O
+g	O
+(	O
+whipping	O
+cream	O
+)	O
+and	O
+from	O
+86	O
+.	O
+7	O
+(	O
+cheese	O
+,	O
+Edam	O
+-	O
+type	O
+)	O
+to	O
+186	O
+.	O
+5	O
+micrograms	O
+/	O
+100	O
+g	O
+(	O
+whipping	O
+cream	O
+)	O
+for	O
+all	O
+-	O
+trans	O
+retinol	O
+and	O
+total	O
+beta	O
+-	O
+carotene	O
+,	O
+respectively	O
+.	O
+
+COGLAB	O
+includes	O
+measures	O
+of	O
+preattentional	O
+,	O
+attentional	O
+,	O
+conceptual	O
+,	O
+and	O
+psychomotor	O
+performance	O
+.	O
+
+With	O
+respect	O
+to	O
+effective	O
+diffusivity	O
+of	O
+platelets	O
+(	O
+De	O
+)	O
+and	O
+the	O
+surface	O
+reactivity	O
+constant	O
+(	O
+K	O
+)	O
+,	O
+less	O
+significant	O
+differences	O
+were	O
+found	O
+among	O
+artificial	O
+materials	O
+.	O
+
+The	O
+two	O
+most	O
+recent	O
+patients	O
+(	O
+35	O
+and	O
+132	O
+days	O
+)	O
+received	O
+only	O
+oral	O
+dipyridamole	O
+(	O
+75	O
+mg	O
+X	O
+3	O
+/	O
+day	O
+)	O
+and	O
+aspirin	O
+(	O
+80	O
+mg	O
+/	O
+day	O
+)	O
+after	O
+the	O
+early	O
+recovery	O
+period	O
+(	O
+four	O
+-	O
+six	O
+days	O
+)	O
+,	O
+resulting	O
+in	O
+normal	O
+prothrombin	B-GENE
+and	O
+partial	O
+thromboplastin	B-GENE
+times	O
+.	O
+
+Middle	O
+-	O
+latency	O
+auditory	O
+evoked	O
+potentials	O
+(	O
+MAEPs	O
+)	O
+were	O
+recorded	O
+in	O
+controls	O
+and	O
+patients	O
+with	O
+focal	O
+lesions	O
+in	O
+dorsolateral	O
+prefrontal	O
+cortex	O
+.	O
+
+Specifically	O
+,	O
+they	O
+were	O
+performed	O
+to	O
+determine	O
+whether	O
+detection	O
+of	O
+envelope	O
+phase	O
+disparity	O
+was	O
+consistent	O
+with	O
+processing	O
+within	O
+a	O
+single	O
+channel	O
+in	O
+which	O
+the	O
+AM	O
+tones	O
+were	O
+simply	O
+added	O
+.	O
+
+Gel	O
+retardation	O
+assays	O
+combined	O
+with	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+and	O
+diethyl	O
+pyrocarbonate	O
+interference	O
+showed	O
+that	O
+a	O
+nuclear	O
+factor	O
+from	O
+differentiated	O
+C2	O
+myotubes	O
+and	O
+BC3H1	O
+myocytes	O
+recognized	O
+a	O
+conserved	O
+A	O
++	O
+T	O
+-	O
+rich	O
+sequence	O
+within	O
+the	O
+peripheral	O
+activating	O
+region	O
+.	O
+
+Such	O
+transgenic	O
+plants	O
+should	O
+enable	O
+not	O
+only	O
+the	O
+mutational	O
+analysis	O
+of	O
+sequence	O
+elements	O
+within	O
+the	O
+replication	O
+origin	O
+region	O
+,	O
+but	O
+also	O
+the	O
+construction	O
+of	O
+a	O
+new	O
+generation	O
+of	O
+vectors	O
+for	O
+gene	O
+amplification	O
+in	O
+plants	O
+,	O
+based	O
+on	O
+a	O
+minimal	O
+virus	O
+replicon	O
+.	O
+
+Ventral	O
+rhinotomy	O
+is	O
+no	O
+more	O
+difficult	O
+than	O
+dorsal	O
+rhinotomy	O
+,	O
+has	O
+less	O
+patient	O
+morbidity	O
+and	O
+fewer	O
+postoperative	O
+complications	O
+,	O
+and	O
+is	O
+more	O
+cosmetically	O
+acceptable	O
+.	O
+
+Four	O
+full	O
+-	O
+thickness	O
+skin	O
+incisions	O
+were	O
+made	O
+in	O
+the	O
+back	O
+of	O
+10	O
+female	O
+pigs	O
+that	O
+treated	O
+twice	O
+a	O
+day	O
+for	O
+14	O
+days	O
+with	O
+2	O
+ml	O
+of	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+300	O
+ng	O
+/	O
+ml	O
+)	O
+or	O
+2	O
+ml	O
+of	O
+Ringer	O
+'	O
+s	O
+lactate	O
+solution	O
+in	O
+a	O
+single	O
+-	O
+blind	O
+,	O
+randomized	O
+fashion	O
+.	O
+
+During	O
+challenge	O
+,	O
+rebiopsy	O
+was	O
+done	O
+when	O
+reticulin	B-GENE
+antibodies	I-GENE
+turned	O
+positive	O
+(	O
+mean	O
+0	O
+.	O
+6	O
+years	O
+,	O
+range	O
+0	O
+.	O
+2	O
+-	O
+2	O
+.	O
+0	O
+)	O
+or	O
+at	O
+the	O
+end	O
+of	O
+the	O
+two	O
+year	O
+study	O
+.	O
+
+The	O
+effect	O
+of	O
+iron	O
+intake	O
+on	O
+59Fe	O
+absorption	O
+throughout	O
+pregnancy	O
+,	O
+and	O
+on	O
+maternal	O
+and	O
+fetal	O
+Fe	O
+status	O
+towards	O
+the	O
+end	O
+of	O
+pregnancy	O
+,	O
+was	O
+investigated	O
+in	O
+rats	O
+.	O
+
+The	O
+deduced	O
+protein	O
+sequence	O
+is	O
+characterized	O
+by	O
+a	O
+putative	O
+16	O
+-	O
+residue	O
+amino	O
+-	O
+terminal	O
+signal	O
+peptide	O
+that	O
+is	O
+cleaved	O
+,	O
+resulting	O
+in	O
+a	O
+239	O
+-	O
+residue	O
+polypeptide	O
+.	O
+
+Analysis	O
+of	O
+the	O
+rate	O
+constants	O
+indicated	O
+that	O
+the	O
+isomerization	O
+rate	O
+k12	O
+was	O
+approximately	O
+equal	O
+to	O
+the	O
+apparent	O
+degradation	O
+rate	O
+of	O
+the	O
+delta	O
+3	O
+ester	O
+kdeg	O
+,	O
+and	O
+slower	O
+than	O
+the	O
+hydrolysis	O
+rate	O
+of	O
+the	O
+delta	O
+2	O
+ester	O
+k24	O
+.	O
+
+A	O
+protocol	O
+is	O
+elaborated	O
+for	O
+the	O
+preparation	O
+and	O
+characterization	O
+of	O
+a	O
+quality	O
+control	O
+material	O
+(	O
+QCM	O
+)	O
+containing	O
+intrinsic	O
+concentration	O
+of	O
+cadmium	O
+(	O
+Cd	O
+)	O
+(	O
+0	O
+.	O
+8	O
+microgram	O
+/	O
+L	O
+)	O
+and	O
+lead	O
+(	O
+Pb	O
+)	O
+(	O
+13	O
+.	O
+4	O
+micrograms	O
+/	O
+dL	O
+)	O
+from	O
+bovine	O
+blood	O
+and	O
+an	O
+elevated	O
+QCM	O
+containing	O
+Cd	O
+(	O
+5	O
+.	O
+0	O
+micrograms	O
+/	O
+L	O
+)	O
+,	O
+mercury	O
+(	O
+Hg	O
+)	O
+(	O
+11	O
+.	O
+2	O
+micrograms	O
+/	O
+L	O
+)	O
+,	O
+and	O
+Pb	O
+(	O
+34	O
+.	O
+5	O
+micrograms	O
+/	O
+dL	O
+)	O
+from	O
+bovine	O
+blood	O
+spiked	O
+with	O
+aqueous	O
+spiking	O
+-	O
+solutions	O
+prepared	O
+with	O
+salts	O
+of	O
+Cd	O
+,	O
+Hg	O
+,	O
+and	O
+Pb	O
+.	O
+
+Reagent	O
+strips	O
+are	O
+frequently	O
+used	O
+in	O
+the	O
+practice	O
+of	O
+laboratory	O
+medicine	O
+as	O
+well	O
+as	O
+outside	O
+the	O
+professional	O
+laboratories	O
+.	O
+
+Precipitating	O
+antibodies	O
+for	O
+Thermophilic	O
+actinomycetes	O
+and	O
+M	O
+.	O
+f	O
+.	O
+were	O
+negative	O
+.	O
+
+LON	O
+-	O
+72	O
+(	O
+34	O
+isolates	O
+)	O
+,	O
+LON	O
+-	O
+73	O
+(	O
+1	O
+)	O
+,	O
+LON	O
+-	O
+71	O
+(	O
+2	O
+)	O
+and	O
+LON	O
+-	O
+10	O
+(	O
+2	O
+)	O
+were	O
+found	O
+at	O
+altitudes	O
+around	O
+2000	O
+m	O
+,	O
+3	O
+of	O
+them	O
+in	O
+a	O
+single	O
+village	O
+.	O
+
+Animal	O
+experimental	O
+and	O
+clinical	O
+applications	O
+of	O
+plates	O
+,	O
+screws	O
+and	O
+spinal	O
+segmental	O
+replacement	O
+implants	O
+made	O
+of	O
+this	O
+composite	O
+material	O
+have	O
+shown	O
+good	O
+results	O
+so	O
+far	O
+.	O
+
+Significance	O
+of	O
+delta	O
+-	O
+aminolevulinic	O
+acid	O
+analysis	O
+in	O
+clinical	O
+tests	O
+
+No	O
+changes	O
+were	O
+evident	O
+in	O
+the	O
+FR	O
+-	O
+task	O
+performance	O
+of	O
+controls	O
+that	O
+received	O
+daily	O
+saline	O
+injections	O
+.	O
+
+Although	O
+the	O
+fertility	O
+decline	O
+in	O
+the	O
+black	O
+population	O
+in	O
+the	O
+Mississippi	O
+Delta	O
+between	O
+the	O
+late	O
+1870	O
+'	O
+s	O
+and	O
+early	O
+1930	O
+'	O
+s	O
+closely	O
+paralleled	O
+that	O
+of	O
+the	O
+national	O
+black	O
+population	O
+,	O
+it	O
+rose	O
+much	O
+more	O
+dramatically	O
+in	O
+the	O
+1940	O
+'	O
+s	O
+and	O
+1950	O
+'	O
+s	O
+to	O
+almost	O
+1880	O
+levels	O
+.	O
+
+According	O
+to	O
+their	O
+staining	O
+affinity	O
+for	O
+anti	B-GENE
+-	I-GENE
+T	I-GENE
+antibodies	I-GENE
+,	O
+the	O
+glandular	O
+tissue	O
+cells	O
+were	O
+classified	O
+as	O
+T	B-GENE
+-	O
+,	O
+T	B-GENE
++	O
+,	O
+T	B-GENE
++	O
++	O
+,	O
+and	O
+T	B-GENE
+and	O
+the	O
+annual	O
+changes	O
+in	O
+the	O
+numbers	O
+of	O
+these	O
+cell	O
+populations	O
+,	O
+as	O
+well	O
+as	O
+in	O
+the	O
+volume	O
+occupied	O
+by	O
+the	O
+glandular	O
+tissue	O
+,	O
+were	O
+calculated	O
+.	O
+
+Ampicillin	O
+(	O
+AMP	O
+)	O
+alone	O
+or	O
+with	O
+an	O
+aminoglycoside	O
+(	O
+AMI	O
+)	O
+was	O
+the	O
+treatment	O
+in	O
+9	O
+and	O
+16	O
+cases	O
+,	O
+respectively	O
+.	O
+
+Alkoxymetgyl	O
+-	O
+3	O
+,	O
+4	O
+-	O
+dimethylpyridinium	O
+chlorides	O
+were	O
+synthetized	O
+by	O
+reacting	O
+3	O
+,	O
+4	O
+-	O
+dimethylpyridine	O
+with	O
+chloromethyl	O
+alkyl	O
+ethers	O
+,	O
+while	O
+1	O
+-	O
+ethyloxymethyl	O
+-	O
+3	O
+-	O
+alkylthiomethylimidazolium	O
+chlorides	O
+were	O
+obtained	O
+in	O
+reactions	O
+of	O
+1	O
+-	O
+ethyloxymethylimidazol	O
+with	O
+chloromethyl	O
+alkyl	O
+sulfides	O
+.	O
+
+We	O
+investigated	O
+the	O
+incidence	O
+of	O
+congenital	O
+color	O
+deficiency	O
+among	O
+Koreans	O
+by	O
+the	O
+use	O
+of	O
+H	O
+-	O
+R	O
+-	O
+R	O
+pseudoisochromatic	O
+plates	O
+.	O
+
+Eighty	O
+patients	O
+presenting	O
+to	O
+HGGM	O
+with	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphomas	O
+between	O
+1962	O
+and	O
+1986	O
+,	O
+were	O
+reviewed	O
+.	O
+
+The	O
+relation	O
+between	O
+VE	O
+/	O
+VO2	O
+and	O
+Q	O
+/	O
+VO2	O
+showed	O
+a	O
+significant	O
+negative	O
+correlation	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+93	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Retrograde	O
+filling	O
+consists	O
+in	O
+sealing	O
+endodontics	O
+system	O
+directly	O
+at	O
+the	O
+apical	O
+zone	O
+after	O
+surgical	O
+approach	O
+.	O
+
+Collaborative	O
+study	O
+of	O
+Japanese	O
+Pharmacopoeia	O
+Heparin	O
+Sodium	O
+Reference	O
+Standard	O
+
+Serological	O
+studies	O
+at	O
+the	O
+early	O
+relapse	O
+stage	O
+of	O
+this	O
+disease	O
+showed	O
+increased	O
+serum	B-GENE
+ANA	I-GENE
+,	O
+IgA	B-GENE
+and	O
+IgM	B-GENE
+level	O
+with	O
+normal	O
+IgG	B-GENE
+and	O
+decrease	O
+of	O
+C3	B-GENE
+and	O
+C4	B-GENE
+.	O
+
+The	O
+maximum	O
+stress	O
+due	O
+to	O
+the	O
+hygroscopic	O
+examination	O
+of	O
+the	O
+composite	O
+was	O
+0	O
+.	O
+74	O
+kg	O
+/	O
+mm2	O
+at	O
+equilibrium	O
+of	O
+the	O
+water	O
+absorbed	O
+of	O
+the	O
+composite	O
+.	O
+
+Ischemic	O
+heart	O
+disease	O
+evaluated	O
+by	O
+exercise	O
+stress	O
+thallium	O
+-	O
+201	O
+myocardial	O
+scintigraphy	O
+:	O
+a	O
+comparison	O
+of	O
+SPECT	O
+and	O
+bull	O
+'	O
+s	O
+eye	O
+display	O
+
+Sequence	O
+analysis	O
+of	O
+the	O
+47	B-GENE
+-	I-GENE
+kilodalton	I-GENE
+major	I-GENE
+integral	I-GENE
+membrane	I-GENE
+immunogen	I-GENE
+of	I-GENE
+Treponema	I-GENE
+pallidum	I-GENE
+.	O
+
+Potential	O
+consensus	O
+sequences	O
+for	O
+early	O
+and	O
+late	O
+regulatory	O
+elements	O
+were	O
+identified	O
+.	O
+
+Construction	O
+of	O
+a	O
+RIP1	B-GENE
+deletion	O
+strain	O
+and	O
+isolation	O
+of	O
+temperature	O
+-	O
+sensitive	O
+mutants	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+hypocitraturia	O
+in	O
+type	O
+I	O
+renal	O
+tubular	O
+acidosis	O
+may	O
+be	O
+due	O
+to	O
+a	O
+defect	O
+in	O
+proximal	O
+tubule	O
+function	O
+.	O
+
+Concomitant	O
+chronic	O
+lymphocytic	O
+leukemia	O
+,	O
+acute	O
+myeloid	O
+leukemia	O
+,	O
+and	O
+thrombosis	O
+with	O
+protein	B-GENE
+C	I-GENE
+deficiency	O
+.	O
+
+Vivid	O
+visual	O
+hallucinations	O
+without	O
+other	O
+psychopathology	O
+have	O
+been	O
+reported	O
+for	O
+several	O
+hundred	O
+years	O
+.	O
+
+In	O
+the	O
+whole	O
+group	O
+,	O
+basal	O
+GH	B-GENE
+and	O
+somatomedin	B-GENE
+-	I-GENE
+C	I-GENE
+levels	O
+decreased	O
+from	O
+a	O
+mean	O
+(	O
++	O
+/	O
+-	O
+standard	O
+error	O
+of	O
+the	O
+mean	O
+)	O
+of	O
+52	O
+.	O
+3	O
++	O
+/	O
+-	O
+12	O
+.	O
+7	O
+to	O
+11	O
+.	O
+1	O
++	O
+/	O
+-	O
+6	O
+.	O
+3	O
+ng	O
+/	O
+ml	O
+and	O
+from	O
+7	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+to	O
+2	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+U	O
+/	O
+ml	O
+,	O
+respectively	O
+.	O
+
+Application	O
+of	O
+different	O
+criteria	O
+of	O
+cure	O
+revealed	O
+that	O
+19	O
+patients	O
+(	O
+66	O
+%	O
+)	O
+had	O
+basal	O
+GH	B-GENE
+levels	O
+below	O
+5	O
+ng	O
+/	O
+ml	O
+,	O
+17	O
+patients	O
+(	O
+59	O
+%	O
+)	O
+had	O
+normal	O
+somatomedin	B-GENE
+-	I-GENE
+C	I-GENE
+values	O
+,	O
+16	O
+patients	O
+(	O
+55	O
+%	O
+)	O
+had	O
+complete	O
+GH	B-GENE
+suppression	O
+(	O
+less	O
+than	O
+1	O
+ng	O
+/	O
+ml	O
+)	O
+during	O
+OGTT	O
+,	O
+and	O
+13	O
+patients	O
+(	O
+45	O
+%	O
+)	O
+met	O
+the	O
+above	O
+-	O
+mentioned	O
+criteria	O
+with	O
+disappearance	O
+of	O
+the	O
+paradoxical	O
+GH	B-GENE
+response	O
+to	O
+TRH	B-GENE
+/	O
+GnRH	B-GENE
+test	O
+.	O
+
+It	O
+suggests	O
+a	O
+sequence	O
+of	O
+surgical	O
+planning	O
+that	O
+can	O
+prevent	O
+them	O
+and	O
+also	O
+offers	O
+ways	O
+of	O
+dealing	O
+with	O
+the	O
+problems	O
+should	O
+they	O
+occur	O
+.	O
+
+In	O
+Rat	O
+-	O
+1a	O
+cells	O
+the	O
+expression	O
+of	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+jun	I-GENE
+mRNA	I-GENE
+was	O
+associated	O
+with	O
+the	O
+ability	O
+to	O
+clone	O
+in	O
+soft	O
+agarose	O
+and	O
+form	O
+tumors	O
+in	O
+nude	O
+mice	O
+.	O
+
+Furthermore	O
+,	O
+formation	O
+of	O
+foci	O
+of	O
+transformed	O
+RECs	O
+by	O
+the	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+/	O
+ras	B-GENE
+combination	O
+was	O
+augmented	O
+3	O
+-	O
+fold	O
+by	O
+the	O
+tumor	O
+promoter	O
+phorbol	O
+12	O
+-	O
+tetradecanoate	O
+13	O
+-	O
+acetate	O
+.	O
+
+Platelet	B-GENE
+activating	I-GENE
+factor	I-GENE
+was	O
+given	O
+in	O
+six	O
+doses	O
+at	O
+15	O
+minute	O
+intervals	O
+and	O
+airway	O
+response	O
+measured	O
+as	O
+change	O
+in	O
+partial	O
+expiratory	O
+flow	O
+at	O
+30	O
+%	O
+of	O
+vital	O
+capacity	O
+(	O
+Vp30	O
+)	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
+correlation	O
+between	O
+baseline	O
+PC40	O
+methacholine	O
+and	O
+the	O
+maximal	O
+fall	O
+in	O
+Vp30	O
+after	O
+either	O
+the	O
+first	O
+(	O
+12	O
+micrograms	O
+)	O
+or	O
+the	O
+second	O
+dose	O
+(	O
+24	O
+micrograms	O
+)	O
+of	O
+platelet	B-GENE
+activating	I-GENE
+factor	I-GENE
+.	O
+
+Both	O
+BG	O
+and	O
+IRI	B-GENE
+concentrations	O
+during	O
+the	O
+OGTT	O
+were	O
+the	O
+lowest	O
+in	O
+body	O
+builders	O
+,	O
+medium	O
+in	O
+controls	O
+,	O
+and	O
+the	O
+highest	O
+in	O
+obese	O
+men	O
+.	O
+
+Although	O
+it	O
+is	O
+well	O
+known	O
+that	O
+calcium	O
+channel	O
+blockers	O
+can	O
+influence	O
+contraction	O
+of	O
+vascular	O
+smooth	O
+muscle	O
+,	O
+there	O
+is	O
+less	O
+knowledge	O
+on	O
+its	O
+effect	O
+on	O
+excitation	O
+contraction	O
+coupling	O
+in	O
+the	O
+endocrine	O
+glands	O
+and	O
+more	O
+specifically	O
+on	O
+insulin	B-GENE
+and	O
+glucagon	B-GENE
+release	O
+.	O
+
+Many	O
+studies	O
+have	O
+pointed	O
+out	O
+the	O
+possibility	O
+of	O
+"	O
+masked	O
+"	O
+organic	O
+factors	O
+in	O
+erectile	O
+impotence	O
+,	O
+detectable	O
+only	O
+by	O
+means	O
+of	O
+laboratory	O
+investigations	O
+:	O
+mild	O
+hypogonadism	O
+,	O
+hyperprolactinemia	O
+,	O
+occlusions	O
+selectively	O
+located	O
+at	O
+the	O
+site	O
+of	O
+the	O
+sexual	O
+arteries	O
+,	O
+venous	O
+incompetence	O
+,	O
+subclinical	O
+neuropathies	O
+.	O
+
+The	O
+site	O
+-	O
+specific	O
+DNA	O
+inversion	O
+system	O
+Cin	B-GENE
+encoded	O
+by	O
+the	O
+bacteriophage	O
+P1	O
+consists	O
+of	O
+a	O
+recombinase	B-GENE
+,	O
+two	O
+inverted	O
+crossing	O
+-	O
+over	O
+sites	O
+and	O
+a	O
+recombinational	O
+enhancer	O
+.	O
+
+The	O
+terminator	O
+region	O
+supported	O
+termination	O
+of	O
+transcripts	O
+initiated	O
+by	O
+RNA	B-GENE
+polymerase	I-GENE
+I	I-GENE
+in	O
+vivo	O
+.	O
+
+US	O
+-	O
+Doppler	O
+has	O
+recently	O
+gained	O
+attention	O
+as	O
+a	O
+noninvasive	O
+method	O
+for	O
+the	O
+functional	O
+evaluation	O
+of	O
+arteriovenous	O
+fistulas	O
+(	O
+FAV	O
+)	O
+.	O
+
+Doppler	O
+echo	O
+in	O
+evaluating	O
+arteriovenous	O
+fistulae	O
+for	O
+dialysis	O
+
+Following	O
+the	O
+patients	O
+during	O
+a	O
+course	O
+of	O
+therapy	O
+with	O
+a	O
+selective	O
+vasodilator	O
+calcium	O
+antagonist	O
+,	O
+the	O
+beta	O
+-	O
+adrenergic	O
+reflex	O
+vasodilation	O
+became	O
+substantially	O
+attenuated	O
+but	O
+was	O
+preserved	O
+during	O
+a	O
+placebo	O
+course	O
+of	O
+therapy	O
+.	O
+
+Of	O
+110	O
+previously	O
+untreated	O
+patients	O
+who	O
+had	O
+entered	O
+the	O
+study	O
+of	O
+protocol	O
+TCL821	O
+,	O
+96	O
+were	O
+evaluable	O
+.	O
+
+There	O
+were	O
+3	O
+/	O
+32	O
+(	O
+9	O
+.	O
+4	O
+per	O
+cent	O
+)	O
+adverse	O
+reactions	O
+(	O
+ADRs	O
+)	O
+,	O
+and	O
+one	O
+case	O
+each	O
+of	O
+nausea	O
+,	O
+dizziness	O
+and	O
+increased	O
+menstrual	O
+flow	O
+.	O
+
+More	O
+mRNA	O
+corresponding	O
+to	O
+nagB	B-GENE
+and	O
+nagA	B-GENE
+is	O
+detected	O
+than	O
+that	O
+corresponding	O
+to	O
+the	O
+distal	O
+genes	O
+,	O
+nagC	B-GENE
+and	O
+nagD	B-GENE
+.	O
+
+Tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+(	O
+TNF	B-GENE
+)	O
+is	O
+reported	O
+to	O
+cause	O
+a	O
+shock	O
+syndrome	O
+similar	O
+to	O
+that	O
+produced	O
+by	O
+endotoxin	O
+(	O
+LPS	O
+)	O
+.	O
+
+The	O
+p34	B-GENE
+.	I-GENE
+8	I-GENE
+gene	I-GENE
+has	O
+a	O
+strong	O
+codon	O
+usage	O
+bias	O
+which	O
+is	O
+strikingly	O
+different	O
+from	O
+that	O
+of	O
+the	O
+polyhedrin	B-GENE
+gene	I-GENE
+.	O
+
+Of	O
+the	O
+single	O
+-	O
+stranded	O
+DNA	O
+transformants	O
+,	O
+65	O
+%	O
+resulted	O
+from	O
+replacement	O
+of	O
+the	O
+resident	O
+met2	B-GENE
+mutation	I-GENE
+by	O
+the	O
+exogenous	O
+wild	O
+-	O
+type	O
+allele	O
+.	O
+
+The	O
+results	O
+strongly	O
+support	O
+the	O
+notion	O
+that	O
+the	O
+OBF1	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+and	O
+the	O
+OBF1	B-GENE
+protein	I-GENE
+are	O
+important	O
+for	O
+normal	O
+ARS	O
+function	O
+as	O
+an	O
+origin	O
+of	O
+replication	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+S1	B-GENE
+nuclease	I-GENE
+protection	O
+analysis	O
+of	O
+RNA	O
+preparations	O
+from	O
+several	O
+mouse	O
+tissues	O
+,	O
+both	O
+dhfr	B-GENE
+and	O
+divergent	O
+genes	O
+showed	O
+similar	O
+levels	O
+of	O
+expression	O
+but	O
+did	O
+show	O
+some	O
+specificity	O
+in	O
+start	O
+site	O
+utilization	O
+.	O
+
+Four	O
+out	O
+of	O
+10	O
+patients	O
+showed	O
+clinical	O
+improvement	O
+according	O
+to	O
+Ritchie	O
+-	O
+Index	O
+,	O
+pain	O
+score	O
+,	O
+ESR	O
+and	O
+CRP	B-GENE
+.	O
+
+62	O
+:	O
+2491	O
+-	O
+2499	O
+,	O
+1987	O
+)	O
+.	O
+
+Survival	O
+rates	O
+for	O
+the	O
+original	O
+treatment	O
+group	O
+were	O
+84	O
+.	O
+5	O
+%	O
+and	O
+57	O
+.	O
+6	O
+%	O
+at	O
+12	O
+and	O
+21	O
+months	O
+,	O
+respectively	O
+;	O
+for	O
+the	O
+delayed	O
+treatment	O
+group	O
+,	O
+78	O
+.	O
+8	O
+%	O
+and	O
+64	O
+.	O
+6	O
+%	O
+at	O
+12	O
+and	O
+21	O
+months	O
+,	O
+respectively	O
+,	O
+and	O
+78	O
+.	O
+8	O
+%	O
+and	O
+47	O
+.	O
+5	O
+%	O
+at	O
+12	O
+and	O
+21	O
+months	O
+,	O
+respectively	O
+,	O
+for	O
+77	O
+subjects	O
+with	O
+AIDS	O
+and	O
+93	O
+.	O
+0	O
+%	O
+and	O
+71	O
+.	O
+8	O
+%	O
+,	O
+respectively	O
+,	O
+for	O
+50	O
+subjects	O
+with	O
+AIDS	O
+-	O
+related	O
+complex	O
+in	O
+the	O
+original	O
+treatment	O
+group	O
+.	O
+
+The	O
+products	O
+of	O
+genes	O
+ura10	B-GENE
+and	O
+ura3	B-GENE
+are	O
+proposed	O
+to	O
+participate	O
+in	O
+the	O
+channeling	O
+of	O
+orotidine	O
+monophosphate	O
+.	O
+
+After	O
+the	O
+application	O
+of	O
+RS	O
+86	O
+,	O
+REM	O
+latency	O
+was	O
+shortened	O
+in	O
+all	O
+groups	O
+under	O
+investigation	O
+.	O
+
+Hybridization	O
+analysis	O
+showed	O
+that	O
+the	O
+size	O
+of	O
+the	O
+mRNA	O
+is	O
+about	O
+1	O
+.	O
+4	O
+kilobases	O
+.	O
+
+Agranulocytosis	O
+treatment	O
+with	O
+rhGM	B-GENE
+-	I-GENE
+CSF	I-GENE
+
+The	O
+R	B-GENE
+.	I-GENE
+meliloti	I-GENE
+nifH	I-GENE
+promoter	I-GENE
+but	O
+not	O
+the	O
+K	B-GENE
+.	I-GENE
+pneumoniae	I-GENE
+nifH	I-GENE
+promoter	I-GENE
+showed	O
+sigma	B-GENE
+54	I-GENE
+-	O
+dependent	O
+methylation	O
+protection	O
+of	O
+guanine	O
+residues	O
+at	O
+-	O
+14	O
+,	O
+-	O
+25	O
+and	O
+-	O
+26	O
+,	O
+the	O
+most	O
+conserved	O
+nucleotides	O
+characteristic	O
+of	O
+sigma	B-GENE
+54	I-GENE
+-	I-GENE
+dependent	I-GENE
+promoters	I-GENE
+.	O
+
+Major	O
+clinical	O
+symptoms	O
+of	O
+the	O
+disease	O
+were	O
+defined	O
+in	O
+this	O
+group	O
+of	O
+patients	O
+.	O
+
+Routine	O
+clinical	O
+analysis	O
+revealed	O
+lower	O
+hematocrit	O
+and	O
+hemoglobin	B-GENE
+,	O
+and	O
+elevated	O
+BUN	O
+and	O
+alkaline	B-GENE
+phosphatase	I-GENE
+in	O
+the	O
+treated	O
+group	O
+.	O
+
+To	O
+assess	O
+the	O
+health	O
+significance	O
+of	O
+the	O
+early	O
+renal	O
+changes	O
+after	O
+chronic	O
+exposure	O
+to	O
+cadmium	O
+,	O
+23	O
+workers	O
+removed	O
+from	O
+exposure	O
+because	O
+of	O
+the	O
+discovery	O
+of	O
+an	O
+increased	O
+urinary	O
+excretion	O
+of	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+or	O
+retinol	B-GENE
+binding	I-GENE
+protein	I-GENE
+,	O
+or	O
+both	O
+,	O
+have	O
+been	O
+examined	O
+once	O
+a	O
+year	O
+for	O
+five	O
+years	O
+.	O
+
+In	O
+order	O
+to	O
+study	O
+the	O
+structural	O
+and	O
+functional	O
+organization	O
+of	O
+the	O
+eukaryotic	O
+nucleolus	O
+,	O
+we	O
+have	O
+started	O
+to	O
+isolate	O
+and	O
+characterize	O
+nucleolar	O
+components	O
+of	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+A	O
+transcription	O
+factor	O
+exclusion	O
+assay	O
+was	O
+used	O
+to	O
+show	O
+that	O
+the	O
+PCF1	B-GENE
+mutation	I-GENE
+affects	O
+two	O
+distinct	O
+stages	O
+in	O
+transcription	O
+:	O
+one	O
+prior	O
+to	O
+and	O
+one	O
+after	O
+stable	O
+complex	O
+formation	O
+;	O
+and	O
+that	O
+these	O
+effects	O
+are	O
+mediated	O
+by	O
+a	O
+component	O
+of	O
+the	O
+stable	O
+complex	O
+.	O
+
+Psychiatry	O
+and	O
+the	O
+skin	O
+.	O
+
+These	O
+adverse	O
+effects	O
+usually	O
+abate	O
+with	O
+time	O
+.	O
+
+The	O
+cytosolic	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferases	I-GENE
+(	O
+GSTs	B-GENE
+,	O
+EC	B-GENE
+2	I-GENE
+.	I-GENE
+5	I-GENE
+.	I-GENE
+1	I-GENE
+.	I-GENE
+18	I-GENE
+)	O
+are	O
+a	O
+superfamily	O
+of	O
+dimeric	O
+isoenzymes	O
+which	O
+catalyze	O
+the	O
+conjugation	O
+of	O
+electrophilic	O
+substrates	O
+with	O
+glutathione	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+3	O
+'	O
+-	O
+untranslated	O
+regions	O
+of	O
+pmGT10	B-GENE
+display	O
+a	O
+marked	O
+degree	O
+of	O
+homology	O
+to	O
+the	O
+3	O
+'	O
+region	O
+of	O
+the	O
+rat	B-GENE
+Yb1	I-GENE
+gene	I-GENE
+,	O
+while	O
+this	O
+region	O
+of	O
+pmGT2	B-GENE
+displays	O
+marked	O
+homology	O
+to	O
+the	O
+corresponding	O
+region	O
+of	O
+the	O
+rat	B-GENE
+Yb2	I-GENE
+gene	I-GENE
+.	O
+
+Model	O
+IV	O
+:	O
+primary	O
+abutments	O
+with	O
+the	O
+lateral	O
+incisor	O
+and	O
+the	O
+second	O
+molar	O
+as	O
+secondary	O
+abutments	O
+.	O
+
+The	O
+incidence	O
+of	O
+fetal	O
+breathing	O
+movements	O
+(	O
+06	O
+.	O
+00	O
+-	O
+10	O
+.	O
+00	O
+h	O
+)	O
+decreased	O
+with	O
+increasing	O
+gestational	O
+age	O
+while	O
+fetal	O
+arterial	O
+concentrations	O
+of	O
+plasma	O
+PGE	O
+increased	O
+significantly	O
+over	O
+the	O
+same	O
+period	O
+of	O
+gestation	O
+.	O
+
+During	O
+the	O
+first	O
+3	O
+min	O
+of	O
+recovery	O
+,	O
+plasma	O
+potassium	O
+fell	O
+rapidly	O
+in	O
+spite	O
+of	O
+nearly	O
+unchanged	O
+blood	O
+acidosis	O
+and	O
+significantly	O
+decreasing	O
+bicarbonate	O
+concentration	O
+.	O
+
+The	O
+present	O
+data	O
+also	O
+suggest	O
+that	O
+when	O
+compared	O
+to	O
+the	O
+systemic	O
+vascular	O
+bed	O
+,	O
+the	O
+pulmonary	O
+vascular	O
+bed	O
+is	O
+less	O
+responsive	O
+to	O
+bolus	O
+administration	O
+of	O
+ET	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+comparison	O
+with	O
+normal	O
+pregnant	O
+women	O
+and	O
+normal	O
+non	O
+-	O
+pregnant	O
+women	O
+,	O
+women	O
+with	O
+PIH	O
+showed	O
+an	O
+increase	O
+in	O
+heart	O
+rate	O
+,	O
+suggesting	O
+an	O
+increased	O
+peripheral	O
+sympathetic	O
+tone	O
+,	O
+and	O
+an	O
+initial	O
+derangement	O
+in	O
+renal	O
+function	O
+as	O
+shown	O
+by	O
+the	O
+increase	O
+in	O
+serum	O
+uric	O
+acid	O
+and	O
+reduction	O
+in	O
+sodium	O
+excretion	O
+and	O
+total	O
+and	O
+fractional	O
+calcium	O
+excretion	O
+at	O
+any	O
+given	O
+level	O
+of	O
+sodium	O
+excretion	O
+.	O
+
+We	O
+have	O
+examined	O
+the	O
+role	O
+of	O
+two	O
+recombination	O
+-	O
+and	O
+repair	O
+-	O
+defective	O
+mutations	O
+,	O
+rad1	B-GENE
+and	O
+rad52	B-GENE
+,	O
+on	O
+direct	O
+repeat	O
+recombination	O
+in	O
+transcriptionally	O
+active	O
+and	O
+inactive	O
+sequences	O
+.	O
+
+The	O
+encoded	O
+protein	O
+has	O
+a	O
+leader	O
+sequence	O
+of	O
+27	O
+amino	O
+acids	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+knowledge	O
+of	O
+the	O
+epidemiology	O
+of	O
+Parkinson	O
+'	O
+s	O
+disease	O
+is	O
+necessary	O
+in	O
+creating	O
+etiological	O
+hypotheses	O
+,	O
+since	O
+only	O
+hypotheses	O
+consistent	O
+with	O
+the	O
+epidemiological	O
+profile	O
+deserve	O
+careful	O
+testing	O
+.	O
+
+The	O
+stereoselectivity	O
+of	O
+drug	O
+action	O
+.	O
+
+Scotchbond	O
+2	O
+showed	O
+the	O
+least	O
+dye	O
+penetration	O
+but	O
+not	O
+statistically	O
+less	O
+than	O
+the	O
+XR	O
+bond	O
+/	O
+Silus	O
+Plus	O
+combination	O
+.	O
+
+A	O
+combination	O
+of	O
+cisplatin	O
+and	O
+5	O
+-	O
+fluorouracil	O
+,	O
+both	O
+administered	O
+4	O
+days	O
+continuously	O
+as	O
+infusion	O
+,	O
+was	O
+assessed	O
+in	O
+advanced	O
+head	O
+and	O
+neck	O
+cancer	O
+.	O
+
+Diagnosis	O
+of	O
+primary	O
+sclerosing	O
+cholangitis	O
+in	O
+a	O
+blood	O
+donor	O
+with	O
+elevated	O
+serum	B-GENE
+alanine	I-GENE
+aminotransferase	I-GENE
+.	O
+
+When	O
+statistically	O
+analyzed	O
+in	O
+various	O
+subgroupings	O
+,	O
+the	O
+obtained	O
+average	O
+sedimentation	O
+coefficients	O
+and	O
+polydispersity	O
+profiles	O
+supported	O
+the	O
+following	O
+conclusions	O
+:	O
+(	O
+a	O
+)	O
+loss	O
+of	O
+proteoglycan	O
+aggregation	O
+and	O
+sedimentability	O
+is	O
+confirmed	O
+to	O
+be	O
+a	O
+primary	O
+sign	O
+of	O
+cartilage	O
+matrix	O
+degradation	O
+;	O
+(	O
+b	O
+)	O
+higher	O
+S	O
+values	O
+for	O
+proteoglycans	O
+of	O
+the	O
+high	O
+weight	O
+(	O
+HW	O
+)	O
+-	O
+bearing	O
+areas	O
+and	O
+lower	O
+values	O
+for	O
+those	O
+of	O
+the	O
+low	O
+weight	O
+(	O
+LW	O
+)	O
+-	O
+bearing	O
+areas	O
+were	O
+a	O
+typical	O
+finding	O
+in	O
+normal	O
+cartilage	O
+samples	O
+;	O
+(	O
+c	O
+)	O
+inversion	O
+of	O
+this	O
+pattern	O
+was	O
+indicative	O
+of	O
+matrix	O
+degradation	O
+,	O
+suggesting	O
+that	O
+the	O
+HW	O
+regions	O
+are	O
+more	O
+affected	O
+than	O
+the	O
+LW	O
+-	O
+bearing	O
+areas	O
+;	O
+(	O
+d	O
+)	O
+the	O
+average	O
+S	O
+value	O
+distribution	O
+across	O
+cartilage	O
+thickness	O
+tended	O
+to	O
+resemble	O
+the	O
+corresponding	O
+proteoglycan	O
+content	O
+versus	O
+distance	O
+from	O
+articular	O
+surface	O
+;	O
+and	O
+(	O
+e	O
+)	O
+the	O
+deepest	O
+cartilage	O
+layer	O
+had	O
+,	O
+in	O
+most	O
+cases	O
+,	O
+the	O
+smallest	O
+amount	O
+of	O
+aggregates	O
+while	O
+the	O
+highest	O
+average	O
+sedimentability	O
+was	O
+observed	O
+at	O
+the	O
+middle	O
+zone	O
+of	O
+the	O
+normal	O
+samples	O
+.	O
+
+End	O
+points	O
+measured	O
+were	O
+perioperative	O
+(	O
+30	O
+-	O
+day	O
+)	O
+myocardial	O
+infarction	O
+(	O
+MI	O
+)	O
+rate	O
+and	O
+death	O
+.	O
+
+The	O
+predicted	O
+molecular	O
+weight	O
+of	O
+the	O
+polyprotein	O
+encoded	O
+by	O
+ORF1	O
+is	O
+33	O
+kilodaltons	O
+(	O
+kDa	O
+)	O
+.	O
+
+Thus	O
+RV	O
+O2	O
+demand	O
+fell	O
+when	O
+RC	O
+O2	O
+supply	O
+was	O
+reduced	O
+,	O
+although	O
+a	O
+flow	O
+reserve	O
+was	O
+available	O
+.	O
+
+An	O
+alternative	O
+method	O
+of	O
+UKM	O
+is	O
+proposed	O
+based	O
+on	O
+collecting	O
+a	O
+small	O
+fraction	O
+of	O
+spent	O
+dialysate	O
+flow	O
+for	O
+3	O
+consecutive	O
+dialyses	O
+.	O
+
+Primer	O
+extension	O
+experiments	O
+indicated	O
+that	O
+the	O
+transcription	O
+initiation	O
+site	O
+mapped	O
+to	O
+a	O
+position	O
+on	O
+gene	B-GENE
+IV	I-GENE
+that	O
+was	O
+analogous	O
+to	O
+that	O
+reported	O
+for	O
+the	O
+structurally	O
+similar	O
+P	B-GENE
+-	I-GENE
+450e	I-GENE
+gene	I-GENE
+.	O
+
+Significantly	O
+,	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+results	O
+demonstrated	O
+that	O
+gene	B-GENE
+IV	I-GENE
+transcripts	I-GENE
+were	O
+associated	O
+with	O
+hepatic	O
+polysome	O
+fractions	O
+,	O
+indicating	O
+their	O
+active	O
+utilization	O
+in	O
+this	O
+tissue	O
+.	O
+
+Validation	O
+of	O
+the	O
+survey	O
+of	O
+work	O
+styles	O
+:	O
+a	O
+profile	O
+measure	O
+of	O
+the	O
+type	O
+A	O
+behaviour	O
+pattern	O
+.	O
+
+Only	O
+one	O
+ADR	O
+was	O
+related	O
+definitely	O
+to	O
+ciprofloxacin	O
+therapy	O
+.	O
+
+HIV	O
+infectiousness	O
+and	O
+the	O
+AIDS	O
+epidemic	O
+.	O
+
+From	O
+day	O
+30	O
+after	O
+turnout	O
+,	O
+the	O
+PFB	O
+-	O
+group	O
+had	O
+significantly	O
+lower	O
+serum	B-GENE
+pepsinogen	I-GENE
+levels	O
+,	O
+which	O
+reflects	O
+the	O
+low	O
+degree	O
+of	O
+abomasal	O
+damage	O
+in	O
+these	O
+animals	O
+.	O
+
+The	O
+corresponding	O
+inhibition	O
+of	O
+acid	B-GENE
+phosphatase	I-GENE
+activity	O
+in	O
+control	O
+male	O
+and	O
+female	O
+guinea	O
+pigs	O
+was	O
+15	O
+.	O
+91	O
+%	O
+and	O
+20	O
+.	O
+33	O
+%	O
+respectively	O
+.	O
+
+Its	O
+clinical	O
+and	O
+histopathologic	O
+characteristics	O
+.	O
+
+Normocapnic	O
+(	O
+PACO2	O
+=	O
+40	O
+mm	O
+Hg	O
+)	O
+ventilatory	O
+drive	O
+increased	O
+significantly	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+in	O
+six	O
+subjects	O
+(	O
+Type	O
+1	O
+response	O
+)	O
+and	O
+decreased	O
+substantially	O
+in	O
+the	O
+others	O
+(	O
+Type	O
+2	O
+response	O
+)	O
+;	O
+with	O
+hypercapnia	O
+,	O
+the	O
+changes	O
+in	O
+drive	O
+were	O
+attenuated	O
+in	O
+both	O
+groups	O
+.	O
+
+Fundus	O
+changes	O
+in	O
+(	O
+type	O
+II	O
+)	O
+mesangiocapillary	O
+glomerulonephritis	O
+simulating	O
+drusen	O
+:	O
+a	O
+histopathological	O
+report	O
+.	O
+
+Chronic	O
+dose	O
+effects	O
+of	O
+methyl	O
+parathion	O
+on	O
+nuthatches	O
+:	O
+cholinesterase	B-GENE
+and	O
+ptilochronology	O
+.	O
+
+Allelic	O
+variation	O
+in	O
+HLA	B-GENE
+-	I-GENE
+B	I-GENE
+and	O
+HLA	B-GENE
+-	I-GENE
+C	I-GENE
+sequences	I-GENE
+and	O
+the	O
+evolution	O
+of	O
+the	O
+HLA	B-GENE
+-	I-GENE
+B	I-GENE
+alleles	I-GENE
+.	O
+
+A	O
+method	O
+for	O
+determining	O
+optimal	O
+development	O
+conditions	O
+by	O
+summary	O
+oxygen	O
+consumption	O
+
+Men	O
+were	O
+more	O
+positive	O
+about	O
+their	O
+physical	O
+fitness	O
+than	O
+women	O
+.	O
+
+Handgrip	O
+dynamometry	O
+was	O
+also	O
+carried	O
+out	O
+in	O
+249	O
+of	O
+the	O
+patients	O
+.	O
+
+In	O
+cerebrospinal	O
+fluid	O
+,	O
+an	O
+ADA	B-GENE
+catalytic	O
+concentration	O
+above	O
+0	O
+.	O
+15	O
+mu	O
+kat	O
+/	O
+L	O
+strongly	O
+suggests	O
+tuberculous	O
+meningitis	O
+in	O
+patients	O
+older	O
+than	O
+7	O
+years	O
+(	O
+sensitivity	O
+1	O
+.	O
+00	O
+,	O
+specificity	O
+0	O
+.	O
+99	O
+and	O
+efficiency	O
+0	O
+.	O
+99	O
+)	O
+.	O
+
+NERVTRACK	O
+contains	O
+4000	O
+anatomical	O
+data	O
+items	O
+arranged	O
+in	O
+a	O
+tree	O
+-	O
+like	O
+manner	O
+reflecting	O
+structural	O
+and	O
+functional	O
+relationships	O
+.	O
+
+Perfusion	O
+washout	O
+:	O
+increasing	O
+a	O
+microvascular	O
+free	O
+flap	O
+tolerance	O
+to	O
+ischemia	O
+.	O
+
+Similarly	O
+,	O
+the	O
+sequence	O
+of	O
+the	O
+U2	B-GENE
+RNA	I-GENE
+region	I-GENE
+shown	O
+to	O
+be	O
+involved	O
+in	O
+pre	O
+-	O
+mRNA	O
+branchpoint	O
+recognition	O
+in	O
+yeast	O
+,	O
+and	O
+exactly	O
+conserved	O
+in	O
+metazoan	B-GENE
+U2	I-GENE
+RNAs	I-GENE
+,	O
+was	O
+totally	O
+divergent	O
+in	O
+trypanosomes	O
+.	O
+
+It	O
+is	O
+striking	O
+that	O
+the	O
+active	O
+CHO	O
+spacer	O
+promoter	O
+violated	O
+the	O
+otherwise	O
+universal	O
+rule	O
+that	O
+metazoan	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+I	I-GENE
+promoters	I-GENE
+all	O
+have	O
+a	O
+G	O
+residue	O
+at	O
+position	O
+-	O
+16	O
+.	O
+
+Significant	O
+intergroup	O
+differences	O
+are	O
+highlighted	O
+for	O
+both	O
+selected	O
+dentoskeletal	O
+and	O
+soft	O
+tissue	O
+profile	O
+variables	O
+.	O
+
+The	O
+author	O
+provides	O
+a	O
+rationale	O
+for	O
+an	O
+interactional	O
+view	O
+and	O
+presents	O
+a	O
+case	O
+in	O
+which	O
+post	O
+-	O
+surgical	O
+hiccups	O
+were	O
+successfully	O
+treated	O
+,	O
+using	O
+principles	O
+developed	O
+by	O
+the	O
+Mental	O
+Research	O
+Institute	O
+.	O
+
+The	O
+relative	O
+toxicity	O
+of	O
+nickel	O
+oxide	O
+(	O
+NiO	O
+)	O
+,	O
+nickel	O
+sulfate	O
+hexahydrate	O
+(	O
+NiSO4	O
+.	O
+6H2O	O
+)	O
+,	O
+and	O
+nickel	O
+subsulfide	O
+(	O
+Ni3S2	O
+)	O
+was	O
+studied	O
+in	O
+F344	O
+/	O
+N	O
+rats	O
+and	O
+B6C3F1	O
+mice	O
+after	O
+inhalation	O
+exposure	O
+for	O
+6	O
+hr	O
+/	O
+day	O
+,	O
+5	O
+days	O
+/	O
+week	O
+,	O
+for	O
+13	O
+weeks	O
+.	O
+
+Light	O
+microscopical	O
+and	O
+routine	O
+immunohistochemical	O
+studies	O
+of	O
+a	O
+cervical	O
+neoplasm	O
+in	O
+a	O
+32	O
+year	O
+old	O
+woman	O
+initially	O
+suggested	O
+a	O
+histiocytic	O
+lymphoma	O
+,	O
+but	O
+histochemical	O
+staining	O
+for	O
+chloroacetate	B-GENE
+esterase	I-GENE
+established	O
+the	O
+correct	O
+diagnosis	O
+.	O
+
+From	O
+the	O
+National	O
+Institutes	O
+of	O
+Health	O
+.	O
+
+Molecular	O
+cloning	O
+and	O
+characterisation	O
+of	O
+the	O
+two	O
+homologous	O
+genes	O
+coding	O
+for	O
+nitrate	B-GENE
+reductase	I-GENE
+in	I-GENE
+tobacco	I-GENE
+.	O
+
+In	O
+the	O
+final	O
+model	O
+,	O
+grade	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0002	O
+)	O
+,	O
+peritoneal	O
+cytologic	O
+results	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0002	O
+)	O
+,	O
+progesterone	B-GENE
+receptor	I-GENE
+status	O
+(	O
+p	O
+=	O
+0	O
+.	O
+004	O
+)	O
+,	O
+and	O
+age	O
+as	O
+a	O
+continuous	O
+variable	O
+(	O
+p	O
+=	O
+0	O
+.	O
+008	O
+)	O
+were	O
+most	O
+closely	O
+associated	O
+with	O
+disease	O
+-	O
+free	O
+survival	O
+.	O
+
+In	O
+contrast	O
+,	O
+despite	O
+external	O
+radiation	O
+therapy	O
+,	O
+brain	O
+metastases	O
+proved	O
+fatal	O
+.	O
+
+COUP	B-GENE
+transcription	I-GENE
+factor	I-GENE
+is	O
+a	O
+member	O
+of	O
+the	O
+steroid	B-GENE
+receptor	I-GENE
+superfamily	I-GENE
+.	O
+
+Cosmid	O
+clones	O
+containing	O
+both	O
+VNTR	O
+sequences	O
+were	O
+identified	O
+,	O
+and	O
+restriction	O
+mapping	O
+showed	O
+them	O
+to	O
+be	O
+less	O
+than	O
+15	O
+kb	O
+apart	O
+.	O
+
+The	O
+oxygen	O
+uptake	O
+(	O
+VO2	O
+)	O
+,	O
+carbon	O
+dioxide	O
+output	O
+(	O
+VCO2	O
+)	O
+,	O
+respiratory	O
+rate	O
+(	O
+fR	O
+)	O
+,	O
+minute	O
+ventilation	O
+(	O
+VE	O
+)	O
+,	O
+alveolar	O
+ventilation	O
+(	O
+VA	O
+)	O
+,	O
+alveolar	O
+oxygen	O
+pressure	O
+(	O
+PAO2	O
+)	O
+,	O
+and	O
+VE	O
+/	O
+VO2	O
+ratio	O
+were	O
+higher	O
+in	O
+the	O
+cows	O
+,	O
+while	O
+the	O
+tidal	O
+volume	O
+(	O
+VT	O
+)	O
+and	O
+physiological	O
+dead	O
+space	O
+(	O
+VD	O
+)	O
+were	O
+larger	O
+in	O
+the	O
+horses	O
+.	O
+
+Epithelial	O
+damage	O
+was	O
+not	O
+observed	O
+in	O
+any	O
+controls	O
+but	O
+was	O
+in	O
+all	O
+tissues	O
+exposed	O
+to	O
+SO2	O
+.	O
+
+The	O
+present	O
+study	O
+investigates	O
+whether	O
+prostaglandins	O
+"	O
+cytoprotect	O
+"	O
+the	O
+gastric	O
+mucosa	O
+against	O
+hemorrhage	O
+-	O
+induced	O
+stress	O
+ulceration	O
+by	O
+assessing	O
+the	O
+influence	O
+of	O
+16	O
+,	O
+16	O
+-	O
+dimethyl	O
+prostaglandin	O
+E2	O
+(	O
+16	O
+,	O
+16	O
+-	O
+dm	O
+PGE2	O
+)	O
+on	O
+gross	O
+and	O
+microscopic	O
+lesion	O
+formation	O
+,	O
+intramucosal	O
+tissue	O
+pH	O
+,	O
+H	O
++	O
+back	O
+-	O
+diffusion	O
+,	O
+and	O
+mucosal	O
+blood	O
+flow	O
+in	O
+rat	O
+gastric	O
+mucosa	O
+exposed	O
+to	O
+luminal	O
+acid	O
+(	O
+100	O
+mM	O
+HCl	O
+)	O
+during	O
+hemorrhagic	O
+shock	O
+(	O
+13	O
+ml	O
+/	O
+kg	O
+for	O
+20	O
+min	O
+)	O
+.	O
+
+Transcripts	O
+characterized	O
+include	O
+(	O
+i	O
+)	O
+abundant	O
+monocistronic	O
+L11e	B-GENE
+and	O
+tricistronic	O
+L1e	B-GENE
+-	O
+L10e	B-GENE
+-	O
+L12e	B-GENE
+transcripts	O
+;	O
+(	O
+ii	O
+)	O
+less	O
+abundant	O
+bicistronic	O
+NAB	B-GENE
+-	O
+L11e	B-GENE
+and	O
+monocistronic	O
+NAB	B-GENE
+transcripts	I-GENE
+and	O
+(	O
+iii	O
+)	O
+a	O
+very	O
+rare	O
+ORF	O
+monocistronic	O
+transcript	O
+.	O
+
+Qualitatively	O
+,	O
+the	O
+results	O
+are	O
+similar	O
+for	O
+the	O
+two	O
+species	O
+:	O
+Both	O
+rhesus	O
+monkey	O
+and	O
+man	O
+have	O
+photopic	O
+and	O
+scotopic	O
+branches	O
+,	O
+which	O
+cross	O
+at	O
+approximately	O
+the	O
+same	O
+time	O
+in	O
+the	O
+dark	O
+and	O
+at	O
+approximately	O
+the	O
+same	O
+background	O
+luminance	O
+.	O
+
+At	O
+each	O
+level	O
+of	O
+PaO2	O
+we	O
+obtained	O
+simultaneous	O
+measures	O
+of	O
+arterial	O
+and	O
+venous	O
+blood	O
+gases	O
+,	O
+venous	O
+lactate	O
+concentration	O
+,	O
+and	O
+changes	O
+in	O
+the	O
+relative	O
+concentrations	O
+of	O
+inorganic	O
+phosphate	O
+,	O
+phosphocreatine	O
+,	O
+and	O
+ATP	O
+measured	O
+with	O
+31P	O
+magnetic	O
+resonance	O
+spectroscopy	O
+.	O
+
+Endometrial	O
+biopsies	O
+and	O
+plasma	O
+oestradiol	O
+(	O
+E2	O
+)	O
+and	O
+progesterone	O
+(	O
+P4	O
+)	O
+levels	O
+in	O
+23	O
+patients	O
+were	O
+evaluated	O
+during	O
+26	O
+replacement	O
+therapy	O
+cycles	O
+for	O
+premature	O
+ovarian	O
+failure	O
+.	O
+
+The	O
+mobility	O
+of	O
+the	O
+upper	O
+and	O
+lower	O
+premolars	O
+under	O
+load	O
+was	O
+investigated	O
+in	O
+relation	O
+to	O
+the	O
+interproximal	O
+contact	O
+and	O
+occlusal	O
+facets	O
+.	O
+
+This	O
+suggested	O
+that	O
+baboon	B-GENE
+liver	I-GENE
+class	I-GENE
+I	I-GENE
+ADH	I-GENE
+is	O
+of	O
+the	O
+same	O
+ancestral	O
+lineage	O
+as	O
+the	O
+human	B-GENE
+ADH	I-GENE
+-	I-GENE
+beta	I-GENE
+.	O
+
+Each	O
+individual	O
+shot	O
+25	O
+bullets	O
+in	O
+about	O
+5	O
+minutes	O
+,	O
+at	O
+an	O
+intensity	O
+level	O
+calculated	O
+at	O
+163	O
+dB	O
+.	O
+
+Dynamic	O
+and	O
+static	O
+scintigrams	O
+,	O
+using	O
+99mtechnetium	O
+methylene	O
+diphosphonate	O
+,	O
+were	O
+obtained	O
+at	O
+zero	O
+,	O
+six	O
+,	O
+and	O
+12	O
+weeks	O
+after	O
+fracture	O
+.	O
+
+On	O
+admission	O
+to	O
+our	O
+department	O
+in	O
+September	O
+,	O
+1987	O
+,	O
+the	O
+patient	O
+was	O
+alert	O
+and	O
+had	O
+spastic	O
+paraparesis	O
+,	O
+the	O
+impairment	O
+of	O
+all	O
+sensory	O
+modalities	O
+below	O
+the	O
+level	O
+of	O
+Th	O
+10	O
+and	O
+urinary	O
+disturbance	O
+.	O
+
+Prostaglandins	O
+and	O
+gallstones	O
+
+The	O
+nature	O
+of	O
+the	O
+process	O
+formed	O
+by	O
+the	O
+successive	O
+occurrences	O
+of	O
+this	O
+arrhythmia	O
+was	O
+studied	O
+in	O
+8	O
+patients	O
+with	O
+a	O
+history	O
+of	O
+symptomatic	O
+paroxysmal	O
+AF	O
+.	O
+
+This	O
+would	O
+have	O
+had	O
+the	O
+effect	O
+of	O
+positioning	O
+the	O
+genes	O
+currently	O
+on	O
+the	O
+long	O
+arm	O
+adjacent	O
+to	O
+the	O
+centromeric	O
+heterochromatin	O
+,	O
+perhaps	O
+resulting	O
+in	O
+a	O
+"	O
+position	O
+effect	O
+"	O
+on	O
+transcription	O
+of	O
+these	O
+genes	O
+.	O
+
+Initial	O
+experience	O
+with	O
+a	O
+microprocessor	O
+controlled	O
+current	O
+based	O
+defibrillator	O
+.	O
+
+Obesity	O
+was	O
+strongly	O
+associated	O
+with	O
+the	O
+proportions	O
+of	O
+nonprotein	O
+-	O
+bound	O
+and	O
+albumin	B-GENE
+-	O
+bound	O
+estradiol	O
+,	O
+and	O
+inversely	O
+associated	O
+with	O
+sex	B-GENE
+hormone	I-GENE
+binding	I-GENE
+globulin	I-GENE
+(	O
+SHBG	B-GENE
+)	O
+levels	O
+and	O
+the	O
+proportion	O
+of	O
+SHBG	B-GENE
+-	O
+bound	O
+estradiol	O
+.	O
+
+Heterogeneous	B-GENE
+nuclear	I-GENE
+ribonucleoprotein	I-GENE
+(	I-GENE
+hnRNP	I-GENE
+)	I-GENE
+core	I-GENE
+protein	I-GENE
+A1	I-GENE
+is	O
+a	O
+major	O
+component	O
+of	O
+mammalian	B-GENE
+hnRNP	I-GENE
+40	I-GENE
+S	I-GENE
+particles	I-GENE
+.	O
+
+Brain	B-GENE
+cholinesterase	I-GENE
+activity	O
+of	O
+nestling	O
+great	O
+egrets	O
+,	O
+snowy	O
+egrets	O
+and	O
+black	O
+-	O
+crowned	O
+night	O
+-	O
+herons	O
+.	O
+inhibition	O
+of	O
+brain	B-GENE
+cholinesterase	I-GENE
+(	O
+ChE	B-GENE
+)	O
+activity	O
+in	O
+birds	O
+is	O
+often	O
+used	O
+to	O
+diagnose	O
+exposure	O
+or	O
+death	O
+from	O
+organophosphorus	O
+or	O
+carbamate	O
+pesticides	O
+.	O
+
+The	O
+effect	O
+of	O
+zinc	O
+deficiency	O
+on	O
+trace	O
+metals	O
+in	O
+the	O
+liver	O
+,	O
+spleen	O
+,	O
+kidney	O
+,	O
+pancreas	O
+and	O
+duodenum	O
+was	O
+investigated	O
+in	O
+the	O
+control	O
+and	O
+zinc	O
+-	O
+deficient	O
+rats	O
+at	O
+17	O
+days	O
+and	O
+20	O
+days	O
+of	O
+pregnancy	O
+.	O
+
+Our	O
+findings	O
+support	O
+the	O
+view	O
+of	O
+a	O
+multifactorial	O
+genesis	O
+of	O
+the	O
+cardiac	O
+involvement	O
+in	O
+uremic	O
+patients	O
+.	O
+
+Heating	O
+cells	O
+to	O
+43	O
+degrees	O
+C	O
+decreased	O
+the	O
+amount	O
+of	O
+newly	O
+synthesized	O
+rRNA	O
+to	O
+less	O
+than	O
+5	O
+%	O
+of	O
+the	O
+control	O
+level	O
+and	O
+led	O
+to	O
+greater	O
+than	O
+95	O
+%	O
+inhibition	O
+of	O
+transcription	O
+termination	O
+at	O
+a	O
+region	O
+355	O
+to	O
+362	O
+nucleotides	O
+downstream	O
+of	O
+the	O
+3	O
+'	O
+end	O
+of	O
+28S	B-GENE
+rRNA	I-GENE
+,	O
+with	O
+readthrough	O
+continuing	O
+into	O
+the	O
+next	O
+transcription	O
+unit	O
+.	O
+
+Deletion	O
+analysis	O
+showed	O
+that	O
+the	O
+NF	B-GENE
+-	I-GENE
+4FA	I-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+4FB	I-GENE
+,	O
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+sequences	O
+are	O
+each	O
+necessary	O
+for	O
+full	O
+enhancer	O
+activity	O
+.	O
+
+Cord	O
+swelling	O
+was	O
+observed	O
+in	O
+2	O
+patients	O
+who	O
+developed	O
+complete	O
+lesions	O
+.	O
+
+Reye	O
+'	O
+s	O
+syndrome	O
+:	O
+reports	O
+of	O
+7	O
+cases	O
+in	O
+the	O
+period	O
+1982	O
+-	O
+1987	O
+
+PULSE	O
+is	O
+used	O
+to	O
+set	O
+such	O
+NMR	O
+spectroscopic	O
+parameters	O
+as	O
+the	O
+delay	O
+and	O
+duration	O
+of	O
+rf	O
+transmit	O
+and	O
+receive	O
+gates	O
+,	O
+rf	O
+phase	O
+,	O
+sampling	O
+times	O
+,	O
+and	O
+such	O
+imaging	O
+parameters	O
+as	O
+rf	O
+pulse	O
+shape	O
+and	O
+gradient	O
+waveforms	O
+.	O
+
+Definite	O
+JPsA	O
+(	O
+24	O
+patients	O
+)	O
+was	O
+defined	O
+as	O
+arthritis	O
+associated	O
+,	O
+but	O
+not	O
+necessarily	O
+coincident	O
+,	O
+with	O
+a	O
+typical	O
+psoriatic	O
+rash	O
+,	O
+or	O
+arthritis	O
+plus	O
+at	O
+least	O
+3	O
+of	O
+4	O
+minor	O
+criteria	O
+:	O
+dactylitis	O
+,	O
+nail	O
+pitting	O
+,	O
+psoriasis	O
+-	O
+like	O
+rash	O
+,	O
+or	O
+family	O
+history	O
+of	O
+psoriasis	O
+.	O
+
+Hence	O
+follows	O
+Kurti	O
+'	O
+s	O
+demand	O
+to	O
+mete	O
+out	O
+appropriate	O
+importance	O
+to	O
+the	O
+arguments	O
+.	O
+
+The	O
+author	O
+gives	O
+an	O
+account	O
+of	O
+antipsychotic	O
+,	O
+analgetic	O
+,	O
+myorelaxing	O
+and	O
+vasodilatating	O
+effects	O
+of	O
+some	O
+calcium	O
+antagonists	O
+,	O
+and	O
+their	O
+clinical	O
+application	O
+is	O
+discussed	O
+.	O
+
+A	O
+correlation	O
+coefficient	O
+was	O
+used	O
+for	O
+assessing	O
+the	O
+similarity	O
+of	O
+each	O
+map	O
+pattern	O
+with	O
+the	O
+normal	O
+mean	O
+IQRST	O
+map	O
+.	O
+
+A	O
+hospital	O
+-	O
+based	O
+study	O
+of	O
+the	O
+relationship	O
+between	O
+retained	O
+placenta	O
+and	O
+mastitis	O
+in	O
+dairy	O
+cows	O
+.	O
+
+This	O
+indicates	O
+that	O
+lipid	O
+peroxidation	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+development	O
+of	O
+senile	O
+cataract	O
+and	O
+,	O
+as	O
+a	O
+direct	O
+consequence	O
+of	O
+retinal	O
+damage	O
+,	O
+also	O
+in	O
+the	O
+pathogenesis	O
+of	O
+cataract	O
+in	O
+diabetes	O
+and	O
+in	O
+severe	O
+myopia	O
+.	O
+
+The	O
+histological	O
+grading	O
+was	O
+certified	O
+in	O
+68	O
+cases	O
+:	O
+12	O
+G1	O
+,	O
+39	O
+G2	O
+,	O
+17	O
+G3	O
+;	O
+extracapsular	O
+spread	O
+was	O
+found	O
+in	O
+20	O
+/	O
+54	O
+cases	O
+(	O
+37	O
+%	O
+)	O
+.	O
+
+Asthma	O
+was	O
+significantly	O
+more	O
+often	O
+associated	O
+with	O
+ASA	O
+group	O
+(	O
+91	O
+%	O
+)	O
+vs	O
+46	O
+%	O
+at	O
+AT	O
+and	O
+in	O
+only	O
+16	O
+%	O
+at	O
+INTR	O
+group	O
+.	O
+
+A	O
+value	O
+of	O
+1	O
+.	O
+1	O
+l	O
+/	O
+kg	O
+was	O
+used	O
+for	O
+V	O
+in	O
+calculating	O
+all	O
+single	O
+sample	O
+estimates	O
+of	O
+clearance	O
+(	O
+CL	O
+)	O
+,	O
+and	O
+a	O
+value	O
+of	O
+4	O
+.	O
+3	O
+l	O
+/	O
+kg	O
+was	O
+used	O
+to	O
+calculate	O
+single	O
+sample	O
+estimates	O
+of	O
+clearance	O
+of	O
+plasma	O
+unbound	O
+drug	O
+(	O
+CLunb	O
+)	O
+.	O
+
+The	O
+solitary	O
+kidney	O
+:	O
+a	O
+model	O
+of	O
+chronic	O
+hyperfiltration	O
+in	O
+humans	O
+.	O
+
+Halothane	O
+is	O
+metabolized	O
+by	O
+an	O
+oxidative	O
+pathway	O
+to	O
+stable	O
+,	O
+nonvolatile	O
+end	O
+products	O
+,	O
+trifluoroacetic	O
+acid	O
+(	O
+TFAA	O
+)	O
+and	O
+bromide	O
+(	O
+Br	O
+-	O
+)	O
+,	O
+and	O
+by	O
+reductive	O
+pathways	O
+to	O
+Br	O
+-	O
+and	O
+inorganic	O
+fluoride	O
+(	O
+F	O
+-	O
+)	O
+.	O
+
+The	O
+values	O
+were	O
+consistently	O
+lower	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+during	O
+summer	O
+(	O
+3	O
+.	O
+79	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+micrograms	O
+/	O
+100	O
+ml	O
+)	O
+,	O
+as	O
+compared	O
+to	O
+winter	O
+(	O
+5	O
+.	O
+06	O
++	O
+/	O
+-	O
+0	O
+.	O
+27	O
+)	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+HAPE	O
+-	O
+S	O
+-	O
+S	O
+are	O
+prone	O
+to	O
+irregular	O
+nocturnal	O
+breathing	O
+patterns	O
+at	O
+high	O
+altitude	O
+,	O
+which	O
+is	O
+associated	O
+with	O
+the	O
+development	O
+of	O
+AMS	O
+,	O
+but	O
+it	O
+was	O
+not	O
+possible	O
+to	O
+determine	O
+whether	O
+these	O
+abnormal	O
+breathing	O
+patterns	O
+are	O
+a	O
+cause	O
+or	O
+an	O
+effect	O
+of	O
+AMS	O
+.	O
+
+It	O
+was	O
+possible	O
+to	O
+classify	O
+the	O
+animals	O
+into	O
+high	O
+and	O
+low	O
+responders	O
+according	O
+to	O
+the	O
+pattern	O
+of	O
+humoral	O
+immune	O
+response	O
+.	O
+
+Heart	O
+rate	O
+(	O
+HR	O
+)	O
+,	O
+rectal	O
+temperature	O
+(	O
+Tre	O
+)	O
+,	O
+blood	O
+pressure	O
+,	O
+temperature	O
+and	O
+relative	O
+humidity	O
+changes	O
+inside	O
+clothing	O
+were	O
+measured	O
+on	O
+18	O
+professional	O
+firemen	O
+(	O
+mean	O
+age	O
+29	O
+.	O
+4	O
++	O
+/	O
+-	O
+7	O
+.	O
+4	O
+yr	O
+,	O
+VO2	O
+max	O
+41	O
+.	O
+4	O
++	O
+8	O
+.	O
+8	O
+ml	O
+kg	O
+-	O
+1	O
+min	O
+-	O
+1	O
+)	O
+wearing	O
+fire	O
+fighter	O
+'	O
+s	O
+uniforms	O
+(	O
+SU	O
+)	O
+or	O
+aluminized	O
+,	O
+fire	O
+resistant	O
+,	O
+impermeable	O
+clothing	O
+with	O
+self	O
+contained	O
+breathing	O
+apparatus	O
+(	O
+FE	O
+)	O
+.	O
+
+The	O
+clinical	O
+tolerance	O
+and	O
+pharmacokinetics	O
+of	O
+FCE	O
+22101	O
+(	O
+sodium	O
+(	O
+5R	O
+,	O
+6S	O
+)	O
+-	O
+6	O
+-	O
+[	O
+(	O
+1R	O
+)	O
+-	O
+hydroxyethyl	O
+]	O
+-	O
+2	O
+-	O
+carbamoyloxymethyl	O
+-	O
+2	O
+-	O
+penem	O
+-	O
+3	O
+-	O
+carboxylate	O
+)	O
+,	O
+a	O
+new	O
+penem	O
+antibiotic	O
+,	O
+have	O
+been	O
+studied	O
+after	O
+giving	O
+a	O
+single	O
+i	O
+.	O
+v	O
+.	O
+dose	O
+of	O
+4	O
+mg	O
+.	O
+kg	O
+-	O
+1	O
+to	O
+ten	O
+healthy	O
+male	O
+volunteers	O
+.	O
+
+DNA	O
+blot	O
+hybridization	O
+suggests	O
+that	O
+the	O
+rat	O
+genome	O
+may	O
+contain	O
+more	O
+than	O
+one	O
+gene	O
+encoding	O
+PtdIns	B-GENE
+transfer	I-GENE
+protein	I-GENE
+.	O
+
+Another	O
+segment	O
+of	O
+CRL3	B-GENE
+(	O
+-	O
+296	O
+to	O
+-	O
+184	O
+)	O
+,	O
+also	O
+displaying	O
+enhancer	O
+function	O
+,	O
+contained	O
+tandem	O
+repeated	O
+sequences	O
+(	O
+DR	O
+-	O
+A1	O
+and	O
+DR	O
+-	O
+A2	O
+)	O
+.	O
+
+1	O
+-	O
+(	O
+1	O
+-	O
+Naphthyl	O
+)	O
+piperazine	O
+(	O
+1	O
+-	O
+NP	O
+)	O
+has	O
+been	O
+reported	O
+to	O
+have	O
+serotonin	O
+antagonist	O
+properties	O
+at	O
+the	O
+5	B-GENE
+-	I-GENE
+HT2	I-GENE
+subtype	I-GENE
+of	O
+receptor	O
+,	O
+and	O
+it	O
+has	O
+been	O
+suggested	O
+that	O
+it	O
+may	O
+have	O
+agonist	O
+actions	O
+at	O
+the	O
+5	B-GENE
+-	I-GENE
+HT1	I-GENE
+site	I-GENE
+.	O
+
+1	O
+-	O
+(	O
+m	O
+-	O
+Chlorophenyl	O
+)	O
+piperazine	O
+(	O
+mCPP	O
+,	O
+0	O
+.	O
+1	O
+-	O
+3	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+1	O
+-	O
+(	O
+m	O
+-	O
+trifluoromethylphenyl	O
+)	O
+piperazine	O
+(	O
+TFMPP	O
+,	O
+0	O
+.	O
+1	O
+-	O
+3	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+both	O
+thought	O
+to	O
+act	O
+primarily	O
+at	O
+5	B-GENE
+-	I-GENE
+HT1	I-GENE
+sites	I-GENE
+,	O
+also	O
+decreased	O
+responding	O
+and	O
+this	O
+effect	O
+was	O
+blocked	O
+by	O
+methysergide	O
+and	O
+by	O
+1	O
+-	O
+NP	O
+,	O
+but	O
+not	O
+by	O
+ketanserin	O
+.	O
+
+The	O
+characteristic	O
+feature	O
+of	O
+liver	O
+and	O
+spleen	O
+MP	O
+function	O
+in	O
+patients	O
+with	O
+VHA	O
+associated	O
+with	O
+HBsAg	B-GENE
+carriership	O
+consisted	O
+in	O
+the	O
+lack	O
+of	O
+the	O
+compensatory	O
+reaction	O
+on	O
+the	O
+part	O
+of	O
+spleen	O
+MP	O
+,	O
+which	O
+was	O
+likely	O
+to	O
+be	O
+connected	O
+with	O
+overstrain	O
+of	O
+long	O
+standing	O
+and	O
+depletion	O
+of	O
+the	O
+MP	O
+system	O
+due	O
+to	O
+permanent	O
+antigenic	O
+stimulation	O
+of	O
+HBsAg	B-GENE
+.	O
+
+Changes	O
+in	O
+xanthine	B-GENE
+oxidase	I-GENE
+activity	O
+in	O
+patients	O
+with	O
+circulatory	O
+failure	O
+
+A	O
+soap	O
+and	O
+water	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+solution	O
+effectively	O
+decontaminated	O
+powdered	O
+stratum	O
+corneum	O
+.	O
+
+The	O
+cytoprotective	O
+and	O
+antiulcer	O
+activities	O
+of	O
+the	O
+antacid	O
+magaldrate	O
+(	O
+ES	O
+Riopan	O
+)	O
+as	O
+well	O
+as	O
+its	O
+effects	O
+on	O
+gastric	O
+mucosal	O
+blood	O
+flow	O
+and	O
+mucus	O
+secretions	O
+,	O
+were	O
+determined	O
+in	O
+the	O
+rat	O
+.	O
+
+The	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+preferentially	O
+infects	O
+CD4	B-GENE
++	I-GENE
+T	O
+lymphocytes	O
+and	O
+may	O
+exist	O
+as	O
+a	O
+latent	O
+provirus	O
+within	O
+these	O
+cells	O
+for	O
+extended	O
+periods	O
+.	O
+
+Histiocytic	O
+panniculitis	O
+was	O
+observed	O
+in	O
+biopsy	O
+specimens	O
+with	O
+cytophagocytosis	O
+.	O
+
+We	O
+have	O
+utilized	O
+the	O
+human	B-GENE
+4F2	I-GENE
+heavy	I-GENE
+chain	I-GENE
+(	O
+4F2HC	B-GENE
+)	O
+gene	O
+as	O
+a	O
+model	O
+system	O
+in	O
+studies	O
+designed	O
+to	O
+elucidate	O
+the	O
+molecular	O
+events	O
+involved	O
+in	O
+regulating	O
+inducible	O
+gene	O
+expression	O
+during	O
+normal	O
+human	O
+T	O
+-	O
+cell	O
+activation	O
+.	O
+
+A	O
+cDNA	O
+encoding	O
+the	O
+NF	B-GENE
+-	I-GENE
+4FB	I-GENE
+enhancer	I-GENE
+binding	I-GENE
+protein	I-GENE
+has	O
+been	O
+cloned	O
+by	O
+screening	O
+a	O
+lambda	O
+gt11	O
+cDNA	O
+library	O
+with	O
+a	O
+rabiolabelled	O
+oligonucleotide	O
+corresponding	O
+to	O
+the	O
+NF	B-GENE
+-	I-GENE
+4FB	I-GENE
+recognition	I-GENE
+sequence	I-GENE
+.	O
+
+Electrocardiographic	O
+right	O
+ventricular	O
+hypertrophy	O
+was	O
+seen	O
+in	O
+4	O
+,	O
+and	O
+biventricular	O
+hypertrophy	O
+in	O
+5	O
+patients	O
+.	O
+
+Sequencing	O
+analysis	O
+revealed	O
+that	O
+the	O
+0	O
+.	O
+54	O
+-	O
+and	O
+0	O
+.	O
+4	O
+-	O
+kb	O
+fragments	O
+are	O
+identical	O
+except	O
+for	O
+150	O
+nucleotides	O
+missing	O
+at	O
+the	O
+5	O
+'	O
+region	O
+of	O
+the	O
+0	O
+.	O
+4	O
+-	O
+kb	O
+fragment	O
+.	O
+
+The	O
+mature	O
+protein	O
+also	O
+contains	O
+a	O
+cysteine	O
+-	O
+rich	O
+,	O
+highly	O
+hydrophilic	O
+region	O
+homologous	O
+to	O
+the	O
+ovomucoid	B-GENE
+serine	I-GENE
+protease	I-GENE
+inhibitors	I-GENE
+(	O
+residues	O
+76	O
+-	O
+132	O
+)	O
+.	O
+
+Oligosynaptic	O
+EPSP	O
+components	O
+were	O
+consistently	O
+modulated	O
+only	O
+in	O
+the	O
+superficial	O
+peroneal	O
+responses	O
+in	O
+flexor	O
+motoneurons	O
+,	O
+which	O
+exhibited	O
+enhanced	O
+amplitude	O
+during	O
+the	O
+flexion	O
+phase	O
+.	O
+
+Experiments	O
+on	O
+23	O
+white	O
+rats	O
+and	O
+10	O
+guinea	O
+pigs	O
+have	O
+shown	O
+that	O
+preliminarily	O
+indomethacin	O
+-	O
+induced	O
+inhibition	O
+of	O
+prostaglandins	O
+synthesis	O
+prevented	O
+development	O
+of	O
+pulmonary	O
+oedema	O
+,	O
+evoked	O
+by	O
+heterologous	O
+serum	O
+in	O
+rats	O
+and	O
+by	O
+vagotomy	O
+in	O
+guinea	O
+pigs	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+lack	O
+of	O
+conservation	O
+of	O
+the	O
+membrane	O
+attachment	O
+sequence	O
+arginine	O
+-	O
+glycine	O
+-	O
+aspartic	O
+acid	O
+argues	O
+against	O
+its	O
+functional	O
+importance	O
+in	O
+CgA	B-GENE
+.	O
+
+Third	O
+-	O
+and	O
+later	O
+-	O
+parity	O
+cows	O
+were	O
+randomly	O
+assigned	O
+after	O
+each	O
+parturition	O
+to	O
+Charolais	O
+and	O
+Red	O
+Poll	O
+bulls	O
+in	O
+multiple	O
+-	O
+sire	O
+pastures	O
+.	O
+
+Within	O
+each	O
+lobe	O
+,	O
+the	O
+PA	O
+dispersion	O
+was	O
+up	O
+to	O
+10	O
+cmH2O	O
+at	O
+CFV	O
+of	O
+90	O
+l	O
+/	O
+min	O
+;	O
+when	O
+flow	O
+decreased	O
+,	O
+PA	O
+at	O
+all	O
+sites	O
+decreased	O
+,	O
+as	O
+did	O
+the	O
+intralobar	O
+dispersion	O
+.	O
+
+The	O
+system	O
+consisted	O
+of	O
+the	O
+intact	O
+canine	O
+heart	O
+connected	O
+to	O
+a	O
+microcomputer	O
+that	O
+operated	O
+as	O
+the	O
+modulated	O
+parasystolic	O
+pacemaker	O
+.	O
+
+In	O
+order	O
+to	O
+identify	O
+and	O
+classify	O
+the	O
+basic	O
+CT	O
+appearances	O
+of	O
+interstitial	O
+pneumonia	O
+,	O
+radiologic	O
+-	O
+pathologic	O
+correlative	O
+study	O
+was	O
+performed	O
+using	O
+inflated	O
+and	O
+fixed	O
+lungs	O
+from	O
+autopsy	O
+and	O
+surgery	O
+.	O
+
+The	O
+disease	O
+ran	O
+an	O
+atypical	O
+course	O
+;	O
+with	O
+early	O
+jaundice	O
+syndrome	O
+,	O
+severe	O
+enterorrhagia	O
+and	O
+late	O
+appearance	O
+of	O
+roseola	O
+.	O
+
+The	O
+transcription	O
+factor	O
+Sp1	B-GENE
+bound	O
+to	O
+eight	O
+sites	O
+,	O
+as	O
+demonstrated	O
+by	O
+footprinting	O
+assays	O
+and	O
+gel	O
+shift	O
+analysis	O
+with	O
+purified	O
+Sp1	B-GENE
+.	O
+
+The	O
+combination	O
+PIP	O
+64	O
+micrograms	O
+-	O
+PEF	O
+4	O
+micrograms	O
+prevents	O
+the	O
+frequent	O
+secondary	O
+regrowth	O
+seen	O
+after	O
+6	O
+hours	O
+with	O
+the	O
+antibiotics	O
+used	O
+alone	O
+.	O
+
+With	O
+a	O
+sample	O
+of	O
+mothers	O
+of	O
+healthy	O
+infants	O
+,	O
+all	O
+three	O
+subscales	O
+of	O
+the	O
+revised	O
+instrument	O
+,	O
+WPL	O
+-	O
+R	O
+,	O
+had	O
+acceptable	O
+levels	O
+of	O
+internal	O
+consistency	O
+at	O
+7	O
+,	O
+30	O
+,	O
+and	O
+90	O
+days	O
+postpartum	O
+,	O
+and	O
+stability	O
+across	O
+administrations	O
+.	O
+
+Since	O
+1948	O
+,	O
+the	O
+use	O
+of	O
+saline	O
+-	O
+washed	O
+red	O
+cells	O
+(	O
+WRBCs	O
+)	O
+has	O
+been	O
+advocated	O
+to	O
+minimize	O
+hemolysis	O
+after	O
+transfusion	O
+to	O
+patients	O
+with	O
+PNH	O
+.	O
+
+In	O
+the	O
+group	O
+of	O
+asthmatics	O
+statistically	O
+significant	O
+correlation	O
+was	O
+found	O
+between	O
+PC20	O
+PGF2	O
+alpha	O
+and	O
+histamine	O
+values	O
+(	O
+r	O
+=	O
+0	O
+.	O
+538	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Acute	O
+experiments	O
+on	O
+nembutal	O
+-	O
+anesthetized	O
+cats	O
+(	O
+50	O
+mg	O
+/	O
+kg	O
+)	O
+were	O
+employed	O
+to	O
+investigate	O
+the	O
+effect	O
+of	O
+1	O
+T	O
+pulsating	O
+magnetic	O
+field	O
+(	O
+PMF	O
+)	O
+on	O
+neuromuscular	O
+system	O
+of	O
+the	O
+leg	O
+.	O
+
+No	O
+significant	O
+differences	O
+were	O
+found	O
+between	O
+the	O
+TS	O
+and	O
+the	O
+PTS	O
+.	O
+
+The	O
+percentages	O
+of	O
+formed	O
+cysts	O
+and	O
+growth	O
+rates	O
+were	O
+monthly	O
+estimated	O
+and	O
+analyzed	O
+rhythmometrically	O
+by	O
+cosinor	O
+for	O
+5	O
+clonal	O
+cultures	O
+of	O
+Scripsiella	O
+trochoidea	O
+Stein	O
+grown	O
+for	O
+2	O
+years	O
+under	O
+laboratory	O
+conditions	O
+,	O
+rended	O
+as	O
+constant	O
+as	O
+possible	O
+from	O
+the	O
+view	O
+point	O
+of	O
+environmental	O
+temperature	O
+(	O
+24	O
++	O
+/	O
+-	O
+1	O
+degree	O
+C	O
+)	O
+,	O
+lighting	O
+(	O
+25	O
+microEin	O
+m	O
+-	O
+2	O
+s	O
+-	O
+1	O
+)	O
+,	O
+and	O
+artificial	O
+seawater	O
+.	O
+
+A	O
+genomic	O
+DNA	O
+clone	O
+encoding	O
+oryzacystatin	B-GENE
+(	O
+Oc	B-GENE
+)	O
+,	O
+a	O
+cysteine	B-GENE
+proteinase	I-GENE
+inhibitor	O
+(	O
+cystatin	B-GENE
+)	O
+of	O
+rice	O
+,	O
+was	O
+isolated	O
+from	O
+a	O
+lambda	O
+EMBL3	O
+phage	O
+library	O
+constructed	O
+with	O
+Sau3AI	B-GENE
+partial	O
+digests	O
+of	O
+rice	O
+chromosomal	O
+DNA	O
+,	O
+by	O
+screening	O
+with	O
+an	O
+oc	B-GENE
+cDNA	I-GENE
+as	O
+a	O
+probe	O
+.	O
+
+The	O
+use	O
+of	O
+an	O
+appropriate	O
+solution	O
+of	O
+methylene	O
+blue	O
+(	O
+0	O
+.	O
+2	O
+%	O
+in	O
+0	O
+.	O
+9	O
+M	O
+NaCl	O
+for	O
+15	O
+min	O
+)	O
+permits	O
+the	O
+staining	O
+of	O
+premalignant	O
+areas	O
+and	O
+CIS	O
+,	O
+and	O
+their	O
+early	O
+diagnosis	O
+.	O
+
+Lower	O
+limits	O
+(	O
+to	O
+10	O
+micrograms	O
+/	O
+kg	O
+)	O
+were	O
+detectable	O
+,	O
+but	O
+with	O
+lower	O
+reliability	O
+(	O
+60	O
+%	O
+)	O
+.	O
+
+Instead	O
+,	O
+some	O
+small	O
+negative	O
+effects	O
+are	O
+observed	O
+,	O
+particularly	O
+involving	O
+effects	O
+of	O
+husbands	O
+'	O
+retirement	O
+on	O
+the	O
+marital	O
+satisfaction	O
+of	O
+employed	O
+wives	O
+.	O
+
+This	O
+in	O
+turn	O
+will	O
+further	O
+enhance	O
+the	O
+role	O
+of	O
+meta	O
+-	O
+analysis	O
+in	O
+helping	O
+clinicians	O
+and	O
+policy	O
+makers	O
+answer	O
+clinical	O
+questions	O
+.	O
+
+The	O
+accuracies	O
+of	O
+presence	O
+or	O
+absence	O
+of	O
+neuroblastoma	O
+were	O
+compared	O
+between	O
+131I	O
+-	O
+MIBG	O
+imaging	O
+and	O
+several	O
+tumor	O
+markers	O
+.	O
+
+The	O
+congenital	O
+forms	O
+(	O
+7	O
+cases	O
+)	O
+all	O
+occurred	O
+in	O
+female	O
+infants	O
+and	O
+involved	O
+the	O
+mucosa	O
+overlying	O
+either	O
+the	O
+anterior	O
+ridge	O
+of	O
+the	O
+maxilla	O
+or	O
+the	O
+mandible	O
+.	O
+
+Immunohistochemical	O
+studies	O
+revealed	O
+positive	O
+staining	O
+for	O
+S100	B-GENE
+protein	I-GENE
+in	O
+all	O
+the	O
+granular	O
+cell	O
+tumors	O
+of	O
+the	O
+adult	O
+but	O
+in	O
+none	O
+of	O
+the	O
+congenital	O
+granular	O
+cell	O
+epulides	O
+.	O
+
+We	O
+also	O
+found	O
+that	O
+the	O
+same	O
+males	O
+,	O
+breeding	O
+in	O
+different	O
+years	O
+on	O
+the	O
+same	O
+territories	O
+,	O
+had	O
+significantly	O
+larger	O
+harems	O
+in	O
+the	O
+years	O
+they	O
+had	O
+familiar	O
+neighbors	O
+.	O
+
+Male	B-GENE
+-	I-GENE
+enhanced	I-GENE
+antigen	I-GENE
+gene	I-GENE
+is	O
+phylogenetically	O
+conserved	O
+and	O
+expressed	O
+at	O
+late	O
+stages	O
+of	O
+spermatogenesis	O
+.	O
+
+In	O
+rats	O
+bearing	O
+Walker	O
+-	O
+256	O
+-	O
+carcinosarcoma	O
+4	O
+-	O
+EPI	O
+was	O
+effective	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Pacing	O
+the	O
+Roux	O
+limb	O
+abolished	O
+the	O
+ectopic	O
+pacemakers	O
+,	O
+restored	O
+the	O
+slow	O
+emptying	O
+of	O
+liquids	O
+to	O
+the	O
+more	O
+rapid	O
+rate	O
+found	O
+in	O
+the	O
+Billroth	O
+dogs	O
+(	O
+t1	O
+/	O
+2	O
+:	O
+paced	O
+Roux	O
+,	O
+72	O
++	O
+/	O
+-	O
+15	O
+minutes	O
+;	O
+Billroth	O
+,	O
+43	O
++	O
+/	O
+-	O
+9	O
+minutes	O
+;	O
+p	O
+greater	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+did	O
+not	O
+change	O
+emptying	O
+of	O
+solids	O
+.	O
+
+The	O
+treatments	O
+were	O
+60	O
+mg	O
+t	O
+.	O
+i	O
+.	O
+d	O
+.	O
+and	O
+120	O
+mg	O
+t	O
+.	O
+i	O
+.	O
+d	O
+.	O
+during	O
+14	O
+days	O
+'	O
+treatment	O
+,	O
+with	O
+the	O
+last	O
+dose	O
+pulsed	O
+with	O
+1	O
+.	O
+85	O
+MBq	O
+[	O
+14C	O
+]	O
+diltiazem	O
+.	O
+
+The	O
+subepicardial	O
+lymphatic	O
+capillaries	O
+were	O
+ramified	O
+and	O
+anastomosed	O
+with	O
+each	O
+other	O
+to	O
+form	O
+a	O
+relatively	O
+dense	O
+network	O
+which	O
+extended	O
+over	O
+the	O
+entire	O
+surface	O
+of	O
+both	O
+ventricles	O
+.	O
+
+The	O
+examination	O
+must	O
+include	O
+T1	O
+and	O
+T2	O
+sequences	O
+and	O
+scans	O
+in	O
+three	O
+planes	O
+.	O
+
+A	O
+great	O
+deal	O
+of	O
+information	O
+is	O
+available	O
+on	O
+the	O
+morphology	O
+of	O
+the	O
+claustrum	O
+in	O
+various	O
+animal	O
+species	O
+,	O
+as	O
+well	O
+as	O
+on	O
+its	O
+neuronal	O
+distribution	O
+and	O
+relationships	O
+with	O
+the	O
+cerebral	O
+cortex	O
+and	O
+other	O
+nuclei	O
+.	O
+
+Low	O
+-	O
+grade	O
+glioma	O
+.	O
+
+In	O
+terms	O
+of	O
+sequence	O
+repetitions	O
+,	O
+seven	O
+tandemly	O
+repeated	O
+copies	O
+of	O
+the	O
+hexanucleotide	O
+ATTGTT	O
+and	O
+three	O
+flanking	O
+regions	O
+of	O
+dyad	O
+symmetry	O
+were	O
+detected	O
+,	O
+all	O
+in	O
+ORF	O
+T3C	O
+.	O
+
+The	O
+significance	O
+of	O
+these	O
+palindromic	O
+domains	O
+in	O
+this	O
+ORF	O
+is	O
+unclear	O
+but	O
+the	O
+coincidence	O
+of	O
+the	O
+end	O
+of	O
+one	O
+larger	O
+palindrome	O
+with	O
+the	O
+end	O
+of	O
+the	O
+translated	O
+protein	O
+sequence	O
+that	O
+has	O
+homology	O
+with	O
+the	O
+B	O
+chain	O
+of	O
+insulin	B-GENE
+suggests	O
+that	O
+the	O
+palindromes	O
+may	O
+divide	O
+the	O
+T2	B-GENE
+protein	I-GENE
+into	O
+several	O
+functional	O
+units	O
+.	O
+
+During	O
+sub	O
+-	O
+maximal	O
+exercise	O
+,	O
+DCR	O
+in	O
+the	O
+UT	O
+dogs	O
+decreased	O
+from	O
+a	O
+resting	O
+value	O
+of	O
+4	O
+.	O
+08	O
++	O
+/	O
+-	O
+0	O
+.	O
+18	O
+mm	O
+Hg	O
+X	O
+ml	O
+-	O
+1	O
+X	O
+min	O
+-	O
+1	O
+to	O
+1	O
+.	O
+91	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+mm	O
+Hg	O
+X	O
+ml	O
+-	O
+1	O
+X	O
+min	O
+-	O
+1	O
+at	O
+a	O
+workload	O
+of	O
+6	O
+.	O
+4	O
+kph	O
+(	O
+speed	O
+)	O
+/	O
+16	O
+%	O
+(	O
+grade	O
+)	O
+.	O
+
+7	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+the	O
+G	B-GENE
+-	I-GENE
+protein	I-GENE
+gene	I-GENE
+family	I-GENE
+may	O
+be	O
+distributed	O
+over	O
+at	O
+least	O
+two	O
+human	O
+chromosomes	O
+.	O
+
+The	O
+major	O
+inserted	O
+DNA	O
+has	O
+no	O
+significant	O
+homology	O
+to	O
+published	O
+human	O
+nucleic	O
+acid	O
+sequences	O
+.	O
+
+We	O
+have	O
+also	O
+found	O
+that	O
+the	O
+in	O
+vitro	O
+interaction	O
+between	O
+the	O
+SV40	O
+octamer	O
+motif	O
+and	O
+the	O
+lymphoid	B-GENE
+cell	I-GENE
+-	I-GENE
+specific	I-GENE
+protein	I-GENE
+oct	I-GENE
+-	I-GENE
+B2	I-GENE
+was	O
+negatively	O
+modulated	O
+by	O
+a	O
+component	O
+present	O
+in	O
+the	O
+nuclear	O
+extracts	O
+from	O
+several	O
+lymphoid	O
+cell	O
+lines	O
+.	O
+
+Anoxia	O
+was	O
+introduced	O
+by	O
+perfusing	O
+the	O
+gill	O
+with	O
+water	O
+deprived	O
+of	O
+oxygen	O
+or	O
+by	O
+halting	O
+the	O
+water	O
+flow	O
+to	O
+the	O
+gill	O
+.	O
+
+Growth	O
+,	O
+4	O
+-	O
+PA	O
+and	O
+14C	O
+turnover	O
+data	O
+indicated	O
+that	O
+WB	O
+contributed	O
+to	O
+B	O
+-	O
+6	O
+intake	O
+of	O
+these	O
+rats	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+revealed	O
+that	O
+these	O
+clones	O
+encode	O
+two	O
+distinct	O
+forms	O
+of	O
+translocase	B-GENE
+.	O
+
+RPA190	B-GENE
+encodes	O
+a	O
+polypeptide	O
+chain	O
+of	O
+186	O
+,	O
+270	O
+daltons	O
+in	O
+a	O
+large	O
+uninterrupted	O
+reading	O
+frame	O
+.	O
+
+Both	O
+the	O
+intact	B-GENE
+A1	I-GENE
+protein	I-GENE
+and	O
+its	O
+proteolytic	O
+fragment	O
+,	O
+the	O
+UP1	B-GENE
+protein	I-GENE
+,	O
+can	O
+be	O
+cleaved	O
+by	O
+Staphylococcus	B-GENE
+aureus	I-GENE
+V	I-GENE
+-	I-GENE
+8	I-GENE
+protease	I-GENE
+to	O
+produce	O
+two	O
+polypeptides	O
+of	O
+92	O
+amino	O
+acids	O
+.	O
+
+Irmiere	O
+,	O
+and	O
+W	O
+.	O
+
+These	O
+offspring	O
+of	O
+the	O
+alpha	B-GENE
+-	I-GENE
+MSH	I-GENE
+treated	O
+mothers	O
+were	O
+less	O
+sensitive	O
+to	O
+pain	O
+and	O
+as	O
+adults	O
+showed	O
+a	O
+reduced	O
+analgesic	O
+response	O
+to	O
+morphine	O
+.	O
+
+Simian	O
+immunodeficiency	O
+virus	O
+(	O
+SIV	O
+)	O
+is	O
+a	O
+lentivirus	O
+with	O
+morphological	O
+and	O
+antigenic	O
+similarities	O
+to	O
+human	O
+immunodeficiency	O
+virus	O
+,	O
+the	O
+causative	O
+agent	O
+of	O
+acquired	O
+immunodeficiency	O
+syndrome	O
+(	O
+AIDS	O
+)	O
+of	O
+humans	O
+.	O
+
+The	O
+lack	O
+of	O
+change	O
+in	O
+the	O
+ratio	O
+of	O
+the	O
+two	O
+spliced	O
+products	O
+expressed	O
+from	O
+either	O
+the	O
+normal	O
+or	O
+the	O
+5	B-GENE
+'	I-GENE
+-	I-GENE
+rearranged	I-GENE
+myb	I-GENE
+further	O
+indicates	O
+that	O
+the	O
+insertion	O
+of	O
+the	O
+unique	O
+121	O
+amino	O
+acids	O
+in	O
+the	O
+larger	O
+myb	B-GENE
+transcripts	I-GENE
+is	O
+not	O
+a	O
+consequence	O
+of	O
+tumor	O
+-	O
+specific	O
+activation	O
+of	O
+the	O
+mouse	B-GENE
+myb	I-GENE
+oncogene	I-GENE
+.	O
+
+The	O
+use	O
+of	O
+CRF	B-GENE
+-	I-GENE
+41	I-GENE
+in	O
+the	O
+differential	O
+diagnosis	O
+of	O
+Cushing	O
+'	O
+s	O
+syndrome	O
+and	O
+obesity	O
+.	O
+
+We	O
+detected	O
+mos	B-GENE
+transcripts	I-GENE
+by	O
+Northern	O
+(	O
+RNA	O
+)	O
+analyses	O
+in	O
+RNA	O
+prepared	O
+from	O
+chicken	O
+and	O
+quail	O
+ovaries	O
+and	O
+testes	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+the	O
+organization	O
+of	O
+functional	O
+units	O
+of	O
+the	O
+72	O
+-	O
+bp	O
+repeat	O
+required	O
+for	O
+transcriptional	O
+enhancement	O
+of	O
+the	O
+early	O
+promoter	O
+is	O
+different	O
+from	O
+that	O
+required	O
+for	O
+late	O
+promoter	O
+function	O
+.	O
+
+Variations	O
+in	O
+the	O
+5	O
+'	O
+half	O
+of	O
+U3	O
+were	O
+primarily	O
+due	O
+to	O
+insertions	O
+and	O
+deletions	O
+.	O
+
+An	O
+analysis	O
+of	O
+the	O
+steady	O
+state	O
+RNA	O
+levels	O
+in	O
+T	O
+-	O
+lymphoid	O
+cell	O
+lines	O
+showed	O
+that	O
+at	O
+least	O
+three	O
+different	O
+incomplete	O
+proviral	O
+transcripts	O
+and	O
+their	O
+spliced	O
+products	O
+made	O
+up	O
+the	O
+majority	O
+of	O
+expressed	O
+RD	B-GENE
+-	I-GENE
+114	I-GENE
+mRNA	I-GENE
+,	O
+and	O
+further	O
+demonstrated	O
+that	O
+partially	O
+deleted	O
+proviral	O
+loci	O
+have	O
+the	O
+potential	O
+to	O
+be	O
+transcriptionally	O
+vigorous	O
+in	O
+certain	O
+feline	O
+cell	O
+types	O
+.	O
+
+Either	O
+two	O
+or	O
+more	O
+different	O
+sequences	O
+can	O
+promote	O
+cleavage	O
+,	O
+or	O
+a	O
+single	O
+element	O
+exists	O
+which	O
+is	O
+long	O
+and	O
+diffuse	O
+.	O
+
+Low	O
+molecular	O
+weight	O
+heparins	O
+have	O
+stimulated	O
+much	O
+interest	O
+because	O
+of	O
+their	O
+supposedly	O
+more	O
+selective	O
+action	O
+on	O
+Xa	B-GENE
+factor	I-GENE
+.	O
+
+Sodium	O
+dodecyl	O
+sulphate	O
+-	O
+induced	O
+cleavage	O
+by	O
+eukaryotic	B-GENE
+topoisomerase	I-GENE
+I	I-GENE
+is	O
+known	O
+to	O
+yield	O
+enzyme	O
+covalently	O
+attached	O
+to	O
+the	O
+3	O
+'	O
+cut	O
+end	O
+of	O
+the	O
+DNA	O
+.	O
+
+Amino	O
+acid	O
+sequence	O
+of	O
+one	O
+human	O
+liver	O
+clone	O
+(	O
+HL	O
+-	O
+14	O
+)	O
+was	O
+identical	O
+to	O
+the	O
+rabbit	B-GENE
+skeletal	I-GENE
+muscle	I-GENE
+phosphatase	I-GENE
+2A	I-GENE
+cDNA	I-GENE
+(	O
+with	O
+97	O
+%	O
+nucleotide	O
+identity	O
+)	O
+.	O
+
+Herpes	O
+virus	O
+infection	O
+was	O
+characterized	O
+by	O
+inversion	O
+of	O
+the	O
+T4	O
+/	O
+T8	O
+ratio	O
+below	O
+1	O
+.	O
+0	O
+(	O
+sensitivity	O
+90	O
+%	O
+,	O
+specificity	O
+88	O
+%	O
+)	O
+,	O
+caused	O
+by	O
+proliferation	O
+of	O
+the	O
+T8	O
+subpopulation	O
+,	O
+which	O
+-	O
+-	O
+compared	O
+with	O
+the	O
+findings	O
+in	O
+patients	O
+with	O
+rejection	O
+crises	O
+-	O
+-	O
+was	O
+significantly	O
+raised	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Quantitative	O
+assays	O
+in	O
+which	O
+the	O
+activity	O
+of	O
+the	O
+synthetic	B-GENE
+alpha	I-GENE
+s	I-GENE
+-	I-GENE
+1	I-GENE
+was	O
+compared	O
+to	O
+that	O
+of	O
+native	O
+purified	O
+human	B-GENE
+erythrocyte	I-GENE
+type	I-GENE
+-	I-GENE
+1	I-GENE
+Gs	I-GENE
+,	O
+indicated	O
+that	O
+the	O
+two	O
+products	O
+are	O
+equipotent	O
+within	O
+a	O
+2	O
+-	O
+fold	O
+margin	O
+of	O
+error	O
+.	O
+
+In	O
+these	O
+cells	O
+,	O
+E2	B-GENE
+proteins	I-GENE
+had	O
+little	O
+or	O
+no	O
+stimulatory	O
+effect	O
+on	O
+the	O
+transcriptional	O
+activity	O
+of	O
+the	O
+HPV	B-GENE
+-	I-GENE
+11	I-GENE
+enhancer	I-GENE
+-	O
+SV40	B-GENE
+promoter	I-GENE
+.	O
+
+The	O
+mechanism	O
+by	O
+which	O
+E2	B-GENE
+-	I-GENE
+C	I-GENE
+represses	O
+E2	B-GENE
+-	I-GENE
+dependent	I-GENE
+enhancer	I-GENE
+activity	O
+most	O
+likely	O
+involves	O
+competition	O
+with	O
+E2	B-GENE
+for	O
+binding	O
+to	O
+a	O
+common	O
+transcriptional	O
+regulatory	O
+site	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+400	O
+WORDS	O
+)	O
+
+Accurate	O
+evaluation	O
+of	O
+the	O
+treatment	O
+results	O
+in	O
+unresectable	O
+lung	O
+cancer	O
+patients	O
+must	O
+take	O
+the	O
+strong	O
+prognostic	O
+factors	O
+into	O
+account	O
+.	O
+
+(	O
+anti	B-GENE
+-	I-GENE
+IIa	I-GENE
+)	O
+and	O
+Holmer	O
+et	O
+al	O
+.	O
+
+Introduction	O
+of	O
+v	B-GENE
+-	I-GENE
+fms	I-GENE
+into	O
+a	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+dependent	O
+murine	O
+macrophage	O
+cell	O
+line	O
+induced	O
+factor	O
+independence	O
+and	O
+tumorigenicity	O
+by	O
+a	O
+nonautocrine	O
+mechanism	O
+.	O
+
+Chronic	O
+E	O
+-	O
+B	O
+virus	O
+infection	O
+terminated	O
+in	O
+malignant	O
+lymphoma	O
+:	O
+a	O
+case	O
+report	O
+
+Whereas	O
+the	O
+muscle	O
+isoform	O
+consists	O
+of	O
+997	O
+amino	O
+acids	O
+and	O
+terminates	O
+with	O
+the	O
+sequence	O
+Ala	O
+-	O
+Ile	O
+-	O
+Leu	O
+-	O
+Glu	O
+,	O
+the	O
+second	O
+isoform	O
+is	O
+1043	O
+amino	O
+acids	O
+in	O
+length	O
+due	O
+to	O
+the	O
+replacement	O
+of	O
+these	O
+last	O
+4	O
+amino	O
+acids	O
+with	O
+a	O
+50	O
+-	O
+amino	O
+acid	O
+sequence	O
+that	O
+contains	O
+a	O
+potential	O
+transmembrane	O
+domain	O
+followed	O
+by	O
+a	O
+consensus	O
+sequence	O
+for	O
+an	O
+N	O
+-	O
+linked	O
+glycosylation	O
+site	O
+.	O
+
+Substitution	O
+of	O
+a	O
+threonine	O
+residue	O
+by	O
+an	O
+alanine	O
+residue	O
+at	O
+position	O
+-	O
+2	O
+(	O
+P2	O
+)	O
+of	O
+this	O
+cleavage	O
+site	O
+abolished	O
+cleavage	O
+,	O
+whereas	O
+substitution	O
+of	O
+a	O
+tyrosine	O
+residue	O
+by	O
+a	O
+phenylalanine	O
+residue	O
+at	O
+amino	O
+acid	O
+position	O
+-	O
+1	O
+(	O
+P1	O
+)	O
+of	O
+the	O
+cleavage	O
+site	O
+did	O
+not	O
+influence	O
+processing	O
+.	O
+
+A	O
+highly	O
+hydrophobic	O
+sequence	O
+located	O
+near	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+extremity	O
+of	O
+the	O
+molecule	O
+most	O
+likely	O
+constitutes	O
+the	O
+anchor	O
+to	O
+the	O
+plasma	O
+membrane	O
+.	O
+
+The	O
+SV40	B-GENE
+enhancer	I-GENE
+augmented	O
+replication	O
+1	O
+.	O
+5	O
+-	O
+10	O
+fold	O
+.	O
+
+One	O
+of	O
+these	O
+,	O
+the	O
+origin	O
+core	O
+,	O
+is	O
+required	O
+only	O
+for	O
+DNA	O
+replication	O
+.	O
+
+Induction	O
+of	O
+proto	B-GENE
+-	I-GENE
+oncogene	I-GENE
+fos	I-GENE
+transcription	O
+through	O
+the	O
+adenylate	B-GENE
+cyclase	I-GENE
+pathway	O
+:	O
+characterization	O
+of	O
+a	O
+cAMP	O
+-	O
+responsive	O
+element	O
+.	O
+
+A	O
+17	O
+-	O
+mer	O
+oligodeoxynucleotide	O
+,	O
+corresponding	O
+to	O
+a	O
+region	O
+of	O
+the	O
+VtHb	B-GENE
+amino	I-GENE
+acid	I-GENE
+sequence	I-GENE
+was	O
+used	O
+as	O
+a	O
+hybridization	O
+probe	O
+to	O
+screen	O
+a	O
+Vitreoscilla	O
+genomic	O
+library	O
+constructed	O
+in	O
+broad	O
+-	O
+host	O
+-	O
+range	O
+cosmid	O
+vector	O
+pVK102	O
+.	O
+
+(	O
+total	O
+soluble	O
+solids	O
+)	O
+and	O
+organoleptic	O
+characteristics	O
+under	O
+the	O
+influence	O
+of	O
+different	O
+treatments	O
+.	O
+
+Causes	O
+of	O
+death	O
+found	O
+in	O
+an	O
+epidemiological	O
+study	O
+of	O
+native	O
+chickens	O
+in	O
+Thai	O
+villages	O
+.	O
+
+The	O
+progression	O
+of	O
+non	O
+-	O
+A	O
+,	O
+non	O
+-	O
+B	O
+hepatitis	O
+to	O
+chronic	O
+diseases	O
+,	O
+and	O
+the	O
+transformation	O
+to	O
+hepatocellular	O
+carcinoma	O
+
+Elevated	O
+IOP	O
+developed	O
+in	O
+35	O
+patients	O
+(	O
+44	O
+eyes	O
+)	O
+during	O
+the	O
+study	O
+.	O
+
+Use	O
+of	O
+serum	O
+thyroglobulin	B-GENE
+determination	O
+in	O
+the	O
+follow	O
+-	O
+up	O
+of	O
+differentiated	O
+carcinomas	O
+of	O
+the	O
+thyroid	O
+
+Poor	O
+response	O
+when	O
+laboratory	O
+recommended	O
+range	O
+for	O
+serum	O
+lithium	O
+is	O
+changed	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+the	O
+effects	O
+of	O
+nebulized	O
+ipratropium	O
+in	O
+patients	O
+with	O
+acute	O
+asthma	O
+in	O
+order	O
+to	O
+determine	O
+whether	O
+it	O
+augments	O
+the	O
+bronchodilator	O
+effect	O
+of	O
+a	O
+beta	O
+agonist	O
+drug	O
+.	O
+
+Further	O
+analysis	O
+of	O
+this	O
+DNA	O
+fragment	O
+showed	O
+that	O
+four	O
+genes	O
+are	O
+present	O
+encoding	O
+proteins	O
+of	O
+16	O
+,	O
+18	O
+.	O
+5	O
+,	O
+21	O
+and	O
+89	O
+kDal	O
+.	O
+
+Hantaan	O
+virus	O
+.	O
+
+Changes	O
+in	O
+dopamine	B-GENE
+receptor	I-GENE
+sensitivity	O
+in	O
+humans	O
+after	O
+heavy	O
+alcohol	O
+intake	O
+.	O
+
+No	O
+significant	O
+differences	O
+between	O
+the	O
+two	O
+treatment	O
+groups	O
+were	O
+found	O
+,	O
+but	O
+rapid	O
+responders	O
+had	O
+a	O
+smaller	O
+mean	O
+initial	O
+platelet	B-GENE
+-	I-GENE
+associated	I-GENE
+IgG	I-GENE
+index	O
+which	O
+returned	O
+more	O
+rapidly	O
+and	O
+more	O
+permanently	O
+to	O
+normal	O
+than	O
+that	O
+of	O
+slow	O
+responders	O
+.	O
+
+Replacement	B-GENE
+variant	I-GENE
+histone	I-GENE
+genes	I-GENE
+contain	O
+intervening	O
+sequences	O
+.	O
+
+Double	O
+-	O
+blind	O
+randomised	O
+trial	O
+of	O
+intravenous	O
+tissue	B-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+versus	O
+placebo	O
+in	O
+acute	O
+myocardial	O
+infarction	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+domains	O
+(	O
+CTDs	O
+)	O
+of	O
+the	O
+RPase	B-GENE
+beta	I-GENE
+subunit	I-GENE
+and	O
+DNA	B-GENE
+primase	I-GENE
+(	O
+dnaG	B-GENE
+protein	I-GENE
+)	O
+were	O
+not	O
+only	O
+strongly	O
+homologous	O
+to	O
+each	O
+other	O
+but	O
+also	O
+considerably	O
+homologous	O
+to	O
+the	O
+RPase	B-GENE
+alpha	I-GENE
+,	O
+suggesting	O
+that	O
+an	O
+alpha	O
+subunit	O
+-	O
+like	O
+enzyme	O
+must	O
+have	O
+been	O
+commonly	O
+ancestral	O
+to	O
+core	B-GENE
+enzyme	I-GENE
+subunits	I-GENE
+and	O
+primase	B-GENE
+.	O
+
+However	O
+,	O
+vancomycin	O
+and	O
+fosfomycin	O
+,	O
+which	O
+revealed	O
+suboptimal	O
+in	O
+vitro	O
+bactericidal	O
+activity	O
+,	O
+proved	O
+as	O
+efficacious	O
+as	O
+penicillin	O
+G	O
+and	O
+imipenem	O
+in	O
+an	O
+experimental	O
+mode	O
+of	O
+murine	O
+gas	O
+gangrene	O
+.	O
+
+Fentanyl	O
+,	O
+a	O
+prototypic	O
+mu	B-GENE
+-	I-GENE
+opiate	I-GENE
+receptor	I-GENE
+agonist	O
+,	O
+has	O
+been	O
+previously	O
+shown	O
+to	O
+produce	O
+a	O
+syndrome	O
+characterized	O
+by	O
+marked	O
+analgesia	O
+and	O
+locomotor	O
+stimulation	O
+as	O
+well	O
+as	O
+tachycardia	O
+,	O
+tachypnoea	O
+and	O
+behavioural	O
+arousal	O
+.	O
+
+Bisoprolol	O
+was	O
+found	O
+to	O
+be	O
+an	O
+effective	O
+beta	B-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+antagonist	O
+,	O
+the	O
+pA2	O
+values	O
+determined	O
+against	O
+isoprenaline	O
+in	O
+guinea	O
+pig	O
+atria	O
+and	O
+tracheal	O
+muscle	O
+being	O
+7	O
+.	O
+45	O
+and	O
+6	O
+.	O
+41	O
+,	O
+respectively	O
+.	O
+
+Output	O
+of	O
+99mTcO	O
+-	O
+4	O
+by	O
+the	O
+parotid	O
+gland	O
+closely	O
+mimicked	O
+fluctuations	O
+in	O
+parotid	O
+saliva	O
+flow	O
+rate	O
+.	O
+
+The	O
+Hagen	O
+-	O
+Poiseuille	O
+equation	O
+is	O
+used	O
+to	O
+assess	O
+the	O
+effects	O
+of	O
+attached	O
+parasites	O
+in	O
+the	O
+foregut	O
+of	O
+Leishmania	O
+-	O
+infected	O
+sandflies	O
+on	O
+blood	O
+flow	O
+.	O
+
+Moreover	O
+,	O
+in	O
+rats	O
+allowed	O
+to	O
+choose	O
+in	O
+a	O
+T	O
+-	O
+maze	O
+between	O
+immediate	O
+-	O
+but	O
+-	O
+small	O
+vs	O
+.	O
+delayed	O
+-	O
+but	O
+-	O
+large	O
+reward	O
+,	O
+BZP	O
+significantly	O
+decreased	O
+the	O
+frequency	O
+with	O
+which	O
+the	O
+delayed	O
+reward	O
+was	O
+chosen	O
+,	O
+with	O
+5	O
+-	O
+HT	O
+uptake	O
+blockers	O
+producing	O
+opposite	O
+effects	O
+.	O
+
+An	O
+endometrial	O
+luteal	O
+phase	O
+deficiency	O
+was	O
+detected	O
+in	O
+15	O
+(	O
+30	O
+%	O
+)	O
+of	O
+aborting	O
+patients	O
+.	O
+
+Prenatal	O
+exposure	O
+to	O
+the	O
+fungicide	O
+dinocap	O
+causes	O
+behavioral	O
+torticollis	O
+,	O
+ballooning	O
+and	O
+cleft	O
+palate	O
+in	O
+mice	O
+,	O
+but	O
+not	O
+rats	O
+or	O
+hamsters	O
+.	O
+
+Reperfusion	O
+with	O
+normal	O
+blood	O
+in	O
+the	O
+beating	O
+,	O
+working	O
+hearts	O
+caused	O
+extensive	O
+structural	O
+damage	O
+,	O
+reduced	O
+reflow	O
+,	O
+and	O
+failed	O
+to	O
+restore	O
+contractility	O
+in	O
+any	O
+instance	O
+(	O
+-	O
+27	O
+%	O
+systolic	O
+shortening	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+sensitivity	O
+of	O
+the	O
+vas	O
+deferens	O
+to	O
+adrenaline	O
+was	O
+also	O
+reduced	O
+in	O
+scorbutic	O
+guinea	O
+pigs	O
+,	O
+thus	O
+decreasing	O
+their	O
+fertility	O
+rate	O
+.	O
+
+In	O
+metabolic	O
+acidosis	O
+there	O
+was	O
+a	O
+marked	O
+stimulation	O
+when	O
+clamped	O
+at	O
+-	O
+10	O
+to	O
+-	O
+100	O
+mV	O
+.	O
+
+On	O
+Days	O
+1	O
+and	O
+14	O
+,	O
+most	O
+young	O
+and	O
+elderly	O
+subjects	O
+exhibited	O
+monoexponential	O
+decline	O
+in	O
+bevantolol	O
+plasma	O
+concentrations	O
+after	O
+absorption	O
+phase	O
+.	O
+
+Mature	O
+and	O
+old	O
+B6AF1	O
+and	O
+B6D2F1	O
+mice	O
+were	O
+given	O
+acidified	O
+tap	O
+water	O
+or	O
+promethazine	O
+HCl	O
+(	O
+a	O
+phenothiazine	O
+with	O
+H1	B-GENE
+receptor	I-GENE
+blocking	O
+activity	O
+)	O
+,	O
+chlorpheniramine	O
+(	O
+an	O
+H1	B-GENE
+blocker	O
+)	O
+or	O
+trifluoperazine	O
+(	O
+a	O
+phenothiazine	O
+with	O
+no	O
+H1	B-GENE
+blocking	O
+activity	O
+)	O
+in	O
+their	O
+drinking	O
+water	O
+,	O
+and	O
+the	O
+effects	O
+of	O
+these	O
+agents	O
+on	O
+bone	O
+mineral	O
+content	O
+were	O
+assessed	O
+by	O
+intermittently	O
+measuring	O
+the	O
+24	O
+-	O
+h	O
+whole	O
+body	O
+retention	O
+of	O
+Tc	O
+99m	O
+methylene	O
+diphosphonate	O
+(	O
+Tc	O
+99m	O
+MDP	O
+,	O
+an	O
+indicator	O
+of	O
+bone	O
+metabolism	O
+)	O
+and	O
+at	O
+the	O
+end	O
+of	O
+the	O
+studies	O
+by	O
+determining	O
+ash	O
+weights	O
+of	O
+femur	O
+,	O
+ilium	O
+and	O
+sacrum	O
+.	O
+
+Present	O
+results	O
+reveal	O
+a	O
+frequency	O
+-	O
+dependent	O
+inhibition	O
+of	O
+ganglionic	O
+transmission	O
+by	O
+diltiazem	O
+,	O
+and	O
+suggest	O
+that	O
+diltiazem	O
+may	O
+depress	O
+excessive	O
+sympathetic	O
+activity	O
+without	O
+affecting	O
+normal	O
+ganglionic	O
+transmission	O
+.	O
+
+Effects	O
+of	O
+a	O
+new	O
+antihypertensive	O
+agent	O
+,	O
+SGB	O
+-	O
+1534	O
+,	O
+on	O
+rat	O
+platelet	O
+aggregation	O
+.	O
+
+Since	O
+the	O
+stability	O
+of	O
+TF1	B-GENE
+resides	O
+in	O
+its	O
+primary	O
+structure	O
+,	O
+we	O
+cloned	O
+a	O
+gene	O
+coding	O
+for	O
+TF1	B-GENE
+,	O
+and	O
+the	O
+primary	O
+structure	O
+of	O
+the	O
+beta	O
+subunit	O
+was	O
+deduced	O
+from	O
+the	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+gene	O
+to	O
+compare	O
+the	O
+sequence	O
+with	O
+those	O
+of	O
+beta	O
+'	O
+s	O
+of	O
+three	O
+major	O
+categories	O
+of	O
+F1	B-GENE
+'	O
+s	O
+;	O
+prokaryotic	O
+membranes	O
+,	O
+chloroplasts	O
+,	O
+and	O
+mitochondria	O
+.	O
+
+Body	O
+temperature	O
+and	O
+overall	O
+conductance	O
+in	O
+the	O
+cold	O
+appear	O
+to	O
+be	O
+more	O
+variable	O
+in	O
+P	O
+.	O
+s	O
+.	O
+campbelli	O
+than	O
+in	O
+nominative	O
+sp	O
+.	O
+
+A	O
+drug	O
+with	O
+ISA	O
+"	O
+down	O
+regulates	O
+"	O
+beta	B-GENE
+receptors	I-GENE
+;	O
+thus	O
+,	O
+when	O
+the	O
+drug	O
+is	O
+withdrawn	O
+there	O
+is	O
+no	O
+post	O
+-	O
+beta	O
+-	O
+blocking	O
+drug	O
+hypersensitivity	O
+in	O
+contrast	O
+to	O
+agents	O
+without	O
+ISA	O
+.	O
+
+Six	O
+patients	O
+with	O
+human	O
+T	O
+-	O
+cell	O
+lymphotropic	O
+virus	O
+type	O
+I	O
+(	O
+HTLV	O
+-	O
+I	O
+)	O
+-	O
+associated	O
+myelopathy	O
+(	O
+HAM	O
+)	O
+were	O
+studied	O
+by	O
+electrophysiologic	O
+methods	O
+.	O
+
+Terazosin	O
+,	O
+a	O
+structural	O
+analog	O
+of	O
+prazosin	O
+,	O
+also	O
+inhibits	O
+alpha	B-GENE
+1	I-GENE
+adrenoceptors	I-GENE
+and	O
+is	O
+recommended	O
+as	O
+once	O
+or	O
+twice	O
+-	O
+daily	O
+therapy	O
+.	O
+
+Testing	O
+blood	O
+donors	O
+for	O
+non	O
+-	O
+A	O
+,	O
+non	O
+-	O
+B	O
+hepatitis	O
+:	O
+irrational	O
+,	O
+perhaps	O
+,	O
+but	O
+inescapable	O
+.	O
+
+Most	O
+patients	O
+with	O
+high	O
+blood	O
+pressure	O
+(	O
+BP	O
+)	O
+can	O
+be	O
+managed	O
+by	O
+using	O
+one	O
+of	O
+4	O
+classes	O
+of	O
+compounds	O
+:	O
+a	O
+diuretic	O
+,	O
+beta	O
+blocker	O
+,	O
+converting	O
+enzyme	O
+inhibitor	O
+or	O
+calcium	O
+antagonist	O
+.	O
+
+In	O
+a	O
+randomised	O
+double	O
+-	O
+blind	O
+study	O
+,	O
+46	O
+first	O
+episode	O
+schizophrenics	O
+were	O
+given	O
+pimozide	O
+or	O
+flupenthixol	O
+for	O
+up	O
+to	O
+5	O
+weeks	O
+;	O
+the	O
+mean	O
+daily	O
+dose	O
+at	O
+the	O
+end	O
+was	O
+18	O
+.	O
+8	O
+mg	O
+pimozide	O
+and	O
+20	O
+mg	O
+flupenthixol	O
+.	O
+
+Somatostatin	B-GENE
+-	O
+producing	O
+endocrine	O
+pancreatic	O
+tumor	O
+in	O
+Recklinghausen	O
+'	O
+s	O
+neurofibromatosis	O
+.	O
+
+Direct	O
+and	O
+inverted	O
+repeat	O
+elements	O
+of	O
+10	O
+,	O
+11	O
+,	O
+16	O
+,	O
+19	O
+,	O
+and	O
+22	O
+nucleotides	O
+(	O
+nt	O
+)	O
+flank	O
+the	O
+promoter	O
+site	O
+.	O
+
+We	O
+have	O
+been	O
+able	O
+to	O
+map	O
+specific	O
+DNA	O
+fragments	O
+at	O
+the	O
+bases	O
+of	O
+chromatin	O
+loops	O
+with	O
+the	O
+help	O
+of	O
+a	O
+novel	O
+extraction	O
+procedure	O
+by	O
+using	O
+lithium	O
+-	O
+3	O
+'	O
+,	O
+5	O
+'	O
+-	O
+diiodosalicylate	O
+.	O
+
+Seventy	O
+-	O
+one	O
+supplementary	O
+doses	O
+of	O
+vecuronium	O
+were	O
+used	O
+for	O
+muscle	O
+relaxation	O
+during	O
+a	O
+22	O
+-	O
+h	O
+-	O
+long	O
+NLA	O
+II	O
+anaesthesia	O
+.	O
+
+Finally	O
+,	O
+the	O
+recovery	O
+indexes	O
+represented	O
+by	O
+the	O
+times	O
+required	O
+for	O
+T1	O
+/	O
+T0	O
+and	O
+T4	O
+/	O
+T1	O
+to	O
+rise	O
+from	O
+25	O
+%	O
+to	O
+75	O
+%	O
+respectively	O
+were	O
+studied	O
+.	O
+
+Transformed	O
+bacterial	O
+colonies	O
+were	O
+screened	O
+for	O
+recombinant	O
+plasmids	O
+containing	O
+cDNA	O
+coding	O
+for	O
+BiP	B-GENE
+by	O
+hybrid	O
+-	O
+selected	O
+mRNA	O
+translation	O
+.	O
+
+DPA	O
+attenuated	O
+the	O
+increase	O
+of	O
+the	O
+intensity	O
+of	O
+the	O
+ischemic	O
+and	O
+pressure	O
+pain	O
+components	O
+with	O
+increasing	O
+ischemia	O
+duration	O
+,	O
+but	O
+only	O
+the	O
+effect	O
+on	O
+the	O
+pressure	O
+pain	O
+component	O
+was	O
+significant	O
+.	O
+
+Topical	O
+1	O
+percent	O
+isoproterenol	O
+in	O
+the	O
+presence	O
+of	O
+the	O
+phosphodiesterase	O
+inhibitor	O
+theophylline	O
+was	O
+tested	O
+for	O
+its	O
+ability	O
+to	O
+stimulate	O
+the	O
+rate	O
+of	O
+aqueous	O
+humor	O
+flow	O
+through	O
+the	O
+anterior	O
+chamber	O
+of	O
+the	O
+normal	O
+and	O
+the	O
+partially	O
+adrenergically	O
+denervated	O
+human	O
+eye	O
+(	O
+Horner	O
+'	O
+s	O
+syndrome	O
+)	O
+.	O
+
+Hyperthyroidism	O
+is	O
+one	O
+of	O
+the	O
+numerous	O
+causes	O
+of	O
+infertility	O
+and	O
+recurrent	O
+abortion	O
+.	O
+
+A	O
+strong	O
+correlation	O
+exists	O
+between	O
+the	O
+numbers	O
+of	O
+CFU	O
+-	O
+GM	O
+transfused	O
+and	O
+the	O
+rate	O
+of	O
+granulocytes	O
+and	O
+platelets	O
+recovery	O
+.	O
+
+Oestrogen	O
+implant	O
+overdose	O
+.	O
+
+Three	O
+sequence	O
+elements	O
+are	O
+shown	O
+to	O
+be	O
+required	O
+for	O
+accurate	O
+and	O
+efficient	O
+transcription	O
+termination	O
+by	O
+RNA	B-GENE
+polymerase	I-GENE
+I	I-GENE
+(	O
+pol	B-GENE
+I	I-GENE
+)	O
+assayed	O
+both	O
+in	O
+a	O
+cell	O
+-	O
+free	O
+transcription	O
+system	O
+and	O
+in	O
+vivo	O
+after	O
+transfection	O
+of	O
+rDNA	O
+minigene	O
+constructs	O
+into	O
+3T6	O
+cells	O
+.	O
+
+A	O
+new	O
+physiopathological	O
+treatment	O
+of	O
+HBV	O
+-	O
+related	O
+polyarteritis	O
+inspired	O
+by	O
+advances	O
+in	O
+the	O
+treatment	O
+of	O
+chronic	O
+active	O
+hepatitis	O
+B	O
+was	O
+tested	O
+in	O
+7	O
+patients	O
+.	O
+
+The	O
+subunit	B-GENE
+-	I-GENE
+a	I-GENE
+gene	I-GENE
+is	O
+preceded	O
+by	O
+a	O
+gene	O
+coding	O
+for	O
+a	O
+small	O
+hydrophobic	O
+protein	O
+,	O
+as	O
+has	O
+been	O
+observed	O
+previously	O
+in	O
+the	O
+atp	B-GENE
+operons	I-GENE
+in	O
+E	O
+.	O
+coli	O
+,	O
+bacterium	O
+PS3	O
+and	O
+cyanobacteria	O
+.	O
+
+Here	O
+,	O
+we	O
+describe	O
+the	O
+isolation	O
+of	O
+bovine	B-GENE
+and	I-GENE
+rat	I-GENE
+GHF	I-GENE
+-	I-GENE
+1	I-GENE
+cDNA	I-GENE
+clones	O
+.	O
+
+To	O
+explore	O
+the	O
+functional	O
+properties	O
+of	O
+the	O
+protein	O
+encoded	O
+by	O
+neu	B-GENE
+,	O
+we	O
+created	O
+a	O
+fusion	O
+gene	O
+that	O
+joins	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+neu	B-GENE
+to	O
+the	O
+extracellular	O
+portion	O
+of	O
+an	O
+immunoglobulin	B-GENE
+heavy	I-GENE
+chain	I-GENE
+.	O
+
+By	O
+sequence	O
+comparison	O
+,	O
+42	O
+blocks	O
+of	O
+homology	O
+are	O
+defined	O
+in	O
+the	O
+5	O
+'	O
+-	O
+terminal	O
+region	O
+,	O
+of	O
+which	O
+36	O
+appear	O
+in	O
+the	O
+CpG	O
+island	O
+and	O
+contain	O
+numerous	O
+conserved	O
+CpG	O
+dinucleotides	O
+.	O
+
+Among	O
+unusual	O
+features	O
+,	O
+we	O
+report	O
+numerous	O
+large	O
+G	O
++	O
+C	O
+-	O
+rich	O
+conserved	O
+sequences	O
+located	O
+in	O
+the	O
+first	O
+intron	O
+.	O
+
+In	O
+the	O
+first	O
+group	O
+,	O
+0	O
+.	O
+02	O
+%	O
+Prazosin	O
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+was	O
+administered	O
+intravenously	O
+for	O
+1	O
+.	O
+5	O
+hours	O
+before	O
+the	O
+application	O
+of	O
+Oxy	O
+-	O
+Hb	O
+or	O
+PGF2	O
+alpha	O
+.	O
+
+A	O
+decamer	O
+sequence	O
+,	O
+5	O
+'	O
+-	O
+CGA	O
+-	O
+CCCCUCC	O
+-	O
+3	O
+'	O
+,	O
+complementary	O
+to	O
+a	O
+conserved	O
+sequence	O
+adjacent	O
+to	O
+the	O
+enzymatic	O
+cleavage	O
+site	O
+on	O
+the	O
+mitochondrial	O
+RNA	O
+substrate	O
+,	O
+is	O
+present	O
+in	O
+the	O
+RNAase	B-GENE
+MRP	I-GENE
+RNA	I-GENE
+.	O
+
+Effects	O
+of	O
+aging	O
+and	O
+beta	O
+-	O
+adrenergic	O
+-	O
+blockade	O
+on	O
+standing	O
+-	O
+induced	O
+QT	O
+/	O
+QS2	O
+changes	O
+.	O
+
+A	O
+patient	O
+with	O
+an	O
+infected	O
+wound	O
+or	O
+one	O
+on	O
+a	O
+primary	O
+area	O
+(	O
+hands	O
+,	O
+feet	O
+,	O
+face	O
+,	O
+or	O
+perineum	O
+)	O
+may	O
+have	O
+to	O
+be	O
+hospitalized	O
+to	O
+ensure	O
+proper	O
+care	O
+.	O
+
+Pharmacology	O
+studies	O
+with	O
+potassium	O
+chloride	O
+and	O
+acetylcholine	O
+suggest	O
+that	O
+raveron	O
+acts	O
+as	O
+a	O
+calcium	O
+antagonist	O
+by	O
+blocking	O
+the	O
+influx	O
+of	O
+extracellular	O
+calcium	O
+.	O
+
+On	O
+admission	O
+to	O
+the	O
+ICU	O
+,	O
+117	O
+patients	O
+(	O
+61	O
+percent	O
+)	O
+had	O
+hypomagnesemia	O
+(	O
+serum	O
+Mg	O
+less	O
+than	O
+1	O
+.	O
+5	O
+mEq	O
+/	O
+dl	O
+)	O
+,	O
+66	O
+patients	O
+(	O
+34	O
+percent	O
+)	O
+had	O
+normomagnesemia	O
+(	O
+1	O
+.	O
+5	O
+to	O
+2	O
+.	O
+0	O
+mEq	O
+/	O
+dl	O
+)	O
+,	O
+and	O
+ten	O
+patients	O
+(	O
+5	O
+percent	O
+)	O
+had	O
+hypermagnesemia	O
+(	O
+greater	O
+than	O
+2	O
+.	O
+0	O
+mEq	O
+/	O
+dl	O
+)	O
+.	O
+
+The	O
+risk	O
+factors	O
+studied	O
+were	O
+male	O
+sex	O
+,	O
+hypertension	O
+,	O
+diabetes	O
+mellitus	O
+,	O
+hypercholesterolemia	O
+,	O
+cigarette	O
+smoking	O
+,	O
+sedentary	O
+life	O
+-	O
+style	O
+,	O
+and	O
+family	O
+history	O
+.	O
+
+Neither	O
+verapamil	O
+nor	O
+nifedipine	O
+changed	O
+collateral	O
+myocardial	O
+blood	O
+flow	O
+from	O
+0	O
+.	O
+10	O
++	O
+/	O
+-	O
+0	O
+.	O
+02	O
+in	O
+the	O
+subendocardium	O
+and	O
+0	O
+.	O
+17	O
++	O
+/	O
+-	O
+0	O
+.	O
+03	O
+ml	O
+/	O
+min	O
+/	O
+g	O
+in	O
+the	O
+subepicardium	O
+.	O
+
+There	O
+were	O
+35	O
+boys	O
+and	O
+15	O
+girls	O
+,	O
+with	O
+a	O
+mean	O
+age	O
+of	O
+five	O
+and	O
+a	O
+half	O
+years	O
+.	O
+
+Controlled	O
+versus	O
+uncontrolled	O
+reperfusion	O
+of	O
+ischemic	O
+myocardium	O
+after	O
+experimental	O
+coronary	O
+artery	O
+occlusion	O
+was	O
+studied	O
+to	O
+determine	O
+the	O
+effect	O
+on	O
+regional	O
+ventricular	O
+wall	O
+motion	O
+and	O
+associated	O
+biochemical	O
+alterations	O
+.	O
+
+Cardiac	O
+disease	O
+was	O
+not	O
+detected	O
+with	O
+M	O
+-	O
+mode	O
+,	O
+2	O
+-	O
+dimensional	O
+real	O
+-	O
+time	O
+or	O
+pulsed	O
+-	O
+wave	O
+Doppler	O
+echocardiography	O
+.	O
+
+Hemodynamic	O
+assessment	O
+was	O
+obtained	O
+before	O
+and	O
+following	O
+administration	O
+of	O
+digoxin	O
+10	O
+micrograms	O
+/	O
+kg	O
+IV	O
+or	O
+dopamine	O
+,	O
+5	O
+to	O
+12	O
+micrograms	O
+/	O
+kg	O
+/	O
+min	O
+IV	O
+.	O
+
+We	O
+conclude	O
+that	O
+at	O
+these	O
+low	O
+levels	O
+studied	O
+,	O
+aluminum	O
+accumulates	O
+in	O
+intestinal	O
+tissue	O
+,	O
+and	O
+that	O
+this	O
+accumulation	O
+is	O
+enhanced	O
+by	O
+citrate	O
+ligand	O
+.	O
+
+Thus	O
+,	O
+the	O
+effects	O
+of	O
+father	O
+absence	O
+under	O
+routine	O
+conditions	O
+in	O
+relatively	O
+healthy	O
+samples	O
+may	O
+exert	O
+no	O
+significant	O
+effects	O
+independent	O
+of	O
+intervening	O
+family	O
+stressors	O
+or	O
+maternal	O
+psychopathology	O
+.	O
+
+Recently	O
+,	O
+an	O
+electrical	O
+-	O
+mechanical	O
+analog	O
+model	O
+of	O
+heat	O
+flow	O
+within	O
+the	O
+brain	O
+has	O
+been	O
+developed	O
+from	O
+which	O
+an	O
+expression	O
+for	O
+CBF	O
+has	O
+been	O
+derived	O
+:	O
+CBF	O
+=	O
+Cb	O
+/	O
+(	O
+tau	O
+rho	O
+c	O
+)	O
+where	O
+tau	O
+is	O
+the	O
+thermal	O
+decay	O
+constant	O
+,	O
+rho	O
+is	O
+the	O
+density	O
+of	O
+blood	O
+,	O
+and	O
+c	O
+is	O
+its	O
+specific	O
+heat	O
+.	O
+
+All	O
+of	O
+the	O
+newly	O
+acquired	O
+proviruses	O
+identified	O
+in	O
+mosaic	O
+founder	O
+SWR	O
+/	O
+J	O
+-	O
+RF	O
+/	O
+J	O
+mice	O
+that	O
+could	O
+be	O
+transmitted	O
+through	O
+the	O
+germ	O
+line	O
+were	O
+also	O
+present	O
+in	O
+somatic	O
+tissues	O
+,	O
+demonstrating	O
+that	O
+viral	O
+integration	O
+occurred	O
+before	O
+the	O
+germ	O
+line	O
+was	O
+set	O
+aside	O
+from	O
+the	O
+somatic	O
+lineages	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+the	O
+cDNA	O
+for	O
+the	O
+human	B-GENE
+U2	I-GENE
+snRNA	I-GENE
+-	I-GENE
+specific	I-GENE
+A	I-GENE
+'	I-GENE
+protein	I-GENE
+.	O
+
+For	O
+the	O
+present	O
+work	O
+we	O
+used	O
+water	O
+saturated	O
+with	O
+a	O
+50	O
+/	O
+50	O
+mixture	O
+of	O
+H2	O
+and	O
+O2	O
+gases	O
+,	O
+for	O
+which	O
+the	O
+heat	O
+defect	O
+is	O
+calculated	O
+to	O
+be	O
+-	O
+2	O
+.	O
+1	O
+%	O
+.	O
+
+During	O
+flexion	O
+whiplash	O
+,	O
+the	O
+torque	O
+at	O
+the	O
+occipital	O
+condyle	O
+reverses	O
+its	O
+direction	O
+at	O
+about	O
+25	O
+ms	O
+after	O
+impact	O
+.	O
+
+The	O
+data	O
+indicates	O
+the	O
+presence	O
+of	O
+5	B-GENE
+-	I-GENE
+HT2	I-GENE
+serotonergic	I-GENE
+receptors	I-GENE
+in	O
+the	O
+bronchial	O
+artery	O
+of	O
+these	O
+species	O
+.	O
+
+Oxfendazole	O
+,	O
+which	O
+was	O
+active	O
+for	O
+the	O
+shortest	O
+time	O
+(	O
+about	O
+65	O
+days	O
+)	O
+from	O
+the	O
+start	O
+of	O
+grazing	O
+(	O
+May	O
+1	O
+)	O
+,	O
+produced	O
+a	O
+78	O
+.	O
+1	O
+per	O
+cent	O
+reduction	O
+in	O
+Ostertagia	O
+species	O
+and	O
+an	O
+84	O
+.	O
+4	O
+per	O
+cent	O
+reduction	O
+in	O
+D	O
+viviparus	O
+.	O
+
+By	O
+adapting	O
+a	O
+method	O
+for	O
+DNA	O
+-	O
+footprinting	O
+using	O
+impure	O
+extracts	O
+of	O
+ner	B-GENE
+overproducing	O
+cells	O
+,	O
+we	O
+were	O
+able	O
+to	O
+determine	O
+that	O
+the	O
+ner	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+are	O
+located	O
+between	O
+nucleotides	O
+1026	O
+and	O
+1058	O
+from	O
+the	O
+Mu	O
+left	O
+end	O
+.	O
+
+Platelet	O
+function	O
+and	O
+platelet	O
+-	O
+polymorphonuclear	O
+-	O
+neutrophil	O
+interaction	O
+in	O
+patients	O
+with	O
+deficient	O
+platelet	B-GENE
+lipoxygenase	I-GENE
+activity	O
+.	O
+
+Spontaneous	O
+degradation	O
+of	O
+atracurium	O
+in	O
+plasma	O
+is	O
+the	O
+major	O
+route	O
+of	O
+elimination	O
+in	O
+man	O
+and	O
+contributes	O
+to	O
+a	O
+short	O
+elimination	O
+half	O
+-	O
+life	O
+(	O
+approximatively	O
+20	O
+min	O
+)	O
+.	O
+
+Transformed	O
+cell	O
+lines	O
+expressing	O
+solely	O
+E1a	B-GENE
+or	O
+E1a	B-GENE
+and	O
+E1b	B-GENE
+gene	I-GENE
+products	I-GENE
+derived	O
+from	O
+these	O
+viruses	O
+display	O
+enhanced	O
+anchorage	O
+-	O
+independent	O
+growth	O
+at	O
+37	O
+degrees	O
+C	O
+versus	O
+32	O
+degrees	O
+C	O
+and	O
+display	O
+a	O
+cytoskeletal	O
+architecture	O
+resembling	O
+untransformed	O
+fibroblastic	O
+CREF	O
+cells	O
+.	O
+
+Partial	O
+N	O
+-	O
+terminal	O
+amino	O
+acid	O
+sequence	O
+analysis	O
+showed	O
+that	O
+the	O
+43K	B-GENE
+and	I-GENE
+42K	I-GENE
+T	I-GENE
+antigens	I-GENE
+contain	O
+methionine	O
+at	O
+residues	O
+1	O
+and	O
+5	O
+,	O
+as	O
+predicted	O
+from	O
+the	O
+DNA	O
+sequence	O
+,	O
+whereas	O
+no	O
+methionine	O
+was	O
+released	O
+from	O
+the	O
+39K	B-GENE
+T	I-GENE
+antigen	I-GENE
+during	O
+the	O
+first	O
+six	O
+cycles	O
+of	O
+Edman	O
+degradation	O
+.	O
+
+Group	O
+A	O
+was	O
+treated	O
+with	O
+three	O
+or	O
+four	O
+doses	O
+of	O
+hepatitis	B-GENE
+B	I-GENE
+immune	I-GENE
+globulin	I-GENE
+(	O
+HBIG	B-GENE
+)	O
+in	O
+one	O
+of	O
+three	O
+different	O
+schedules	O
+.	O
+
+In	O
+the	O
+former	O
+instance	O
+,	O
+in	O
+addition	O
+to	O
+serum	O
+calcium	O
+and	O
+phosphorous	O
+ion	O
+concentrations	O
+,	O
+tissue	O
+pH	O
+,	O
+blood	O
+supply	O
+,	O
+hormones	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+vitamin	O
+D	O
+,	O
+vitamin	O
+A	O
+,	O
+and	O
+various	O
+enzymes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+alkaline	B-GENE
+phosphatase	I-GENE
+and	O
+pyrophosphatase	B-GENE
+)	O
+may	O
+all	O
+play	O
+significant	O
+,	O
+ancillary	O
+,	O
+time	O
+-	O
+dependent	O
+,	O
+but	O
+as	O
+yet	O
+undetermined	O
+roles	O
+.	O
+
+Penicillinase	B-GENE
+production	O
+in	O
+Staphylococcus	O
+aureus	O
+strains	O
+of	O
+clinical	O
+importance	O
+.	O
+
+Thus	O
+,	O
+quantitative	O
+analysis	O
+of	O
+thallium	O
+-	O
+201	O
+uptake	O
+and	O
+washout	O
+provided	O
+objective	O
+evidence	O
+for	O
+improved	O
+myocardial	O
+perfusion	O
+after	O
+coronary	O
+angioplasty	O
+.	O
+
+This	O
+study	O
+reports	O
+the	O
+effects	O
+of	O
+a	O
+preparation	O
+with	O
+50	O
+micrograms	O
+ethinyl	O
+estradiol	O
+and	O
+2	O
+mg	O
+cyproterone	O
+acetate	O
+on	O
+gonadotropins	B-GENE
+,	O
+prolactin	B-GENE
+,	O
+testosterone	O
+,	O
+sex	B-GENE
+hormone	I-GENE
+binding	I-GENE
+globulin	I-GENE
+(	O
+SHBG	B-GENE
+)	O
+,	O
+androstenedione	O
+,	O
+and	O
+calculated	O
+free	O
+testosterone	O
+index	O
+before	O
+and	O
+after	O
+six	O
+months	O
+of	O
+treatment	O
+.	O
+
+In	O
+nine	O
+patients	O
+with	O
+renal	O
+failure	O
+routine	O
+haemodialysis	O
+was	O
+accompanied	O
+by	O
+a	O
+30	O
+per	O
+cent	O
+reduction	O
+in	O
+plasma	O
+ANP	B-GENE
+concentration	O
+.	O
+
+To	O
+investigate	O
+the	O
+effects	O
+of	O
+isotretinoin	O
+on	O
+HDL	B-GENE
+,	O
+we	O
+measured	O
+HDL	B-GENE
+-	I-GENE
+C	I-GENE
+,	O
+HDL	B-GENE
+phospholipids	O
+(	O
+HDL	B-GENE
+-	I-GENE
+PL	I-GENE
+)	O
+,	O
+apoprotein	B-GENE
+A1	I-GENE
+(	O
+apo	B-GENE
+A	I-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+and	O
+HDL	B-GENE
+-	I-GENE
+C	I-GENE
+subfractions	O
+(	O
+HDL2	B-GENE
+-	I-GENE
+C	I-GENE
+and	O
+HDL3	B-GENE
+-	I-GENE
+C	I-GENE
+)	O
+in	O
+24	O
+healthy	O
+,	O
+male	O
+patients	O
+receiving	O
+a	O
+16	O
+-	O
+week	O
+course	O
+of	O
+isotretinoin	O
+(	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+)	O
+for	O
+treatment	O
+of	O
+severe	O
+acne	O
+vulgaris	O
+.	O
+
+The	O
+clinical	O
+picture	O
+and	O
+laboratory	O
+parameters	O
+were	O
+consistent	O
+with	O
+a	O
+serum	O
+sickness	O
+reaction	O
+.	O
+
+Preventive	O
+effect	O
+of	O
+ONO	O
+-	O
+3708	O
+on	O
+thrombosis	O
+and	O
+vasospasms	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+The	O
+frequency	O
+of	O
+PPNG	O
+strains	O
+increased	O
+from	O
+1	O
+.	O
+7	O
+%	O
+in	O
+1981	O
+to	O
+6	O
+.	O
+7	O
+%	O
+in	O
+1985	O
+.	O
+
+Monospecific	O
+antibodies	O
+,	O
+eluted	O
+from	O
+the	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+fusion	O
+protein	O
+of	O
+either	O
+clone	O
+reacted	O
+with	O
+the	O
+U1	B-GENE
+snRNP	I-GENE
+-	O
+specific	O
+A	B-GENE
+antigen	I-GENE
+.	O
+
+The	O
+pathogenesis	O
+of	O
+Limited	O
+Joint	O
+Mobility	O
+(	O
+LJM	O
+)	O
+in	O
+diabetes	O
+is	O
+unknown	O
+,	O
+but	O
+the	O
+abnormality	O
+is	O
+said	O
+to	O
+be	O
+associated	O
+with	O
+an	O
+increased	O
+incidence	O
+of	O
+microangiopathy	O
+.	O
+
+The	O
+experimental	O
+end	O
+points	O
+were	O
+the	O
+time	O
+required	O
+for	O
+treated	O
+tumors	O
+to	O
+reach	O
+3	O
+times	O
+their	O
+treatment	O
+size	O
+,	O
+the	O
+survival	O
+of	O
+stem	O
+cells	O
+in	O
+the	O
+duodenal	O
+crypts	O
+,	O
+and	O
+the	O
+breathing	O
+rate	O
+measured	O
+early	O
+(	O
+19	O
+-	O
+23	O
+weeks	O
+)	O
+and	O
+late	O
+(	O
+41	O
+-	O
+46	O
+weeks	O
+)	O
+after	O
+treatment	O
+.	O
+
+Schedule	O
+2	O
+,	O
+in	O
+which	O
+2	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+c	O
+-	O
+DDP	O
+was	O
+administered	O
+immediately	O
+before	O
+X	O
+-	O
+ray	O
+on	O
+5	O
+consecutive	O
+days	O
+produced	O
+the	O
+highest	O
+degree	O
+of	O
+enhancement	O
+of	O
+radiation	O
+effect	O
+(	O
+expressed	O
+as	O
+dose	O
+-	O
+effect	O
+factor	O
+)	O
+;	O
+and	O
+the	O
+next	O
+greatest	O
+enhancement	O
+was	O
+produced	O
+by	O
+12	O
+mg	O
+/	O
+kg	O
+c	O
+-	O
+DDP	O
+administered	O
+24	O
+h	O
+before	O
+the	O
+start	O
+of	O
+fractionated	O
+daily	O
+radiotherapy	O
+.	O
+
+The	O
+cpc	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+encoded	I-GENE
+transcript	I-GENE
+contains	O
+three	O
+open	O
+reading	O
+frames	O
+,	O
+two	O
+of	O
+which	O
+are	O
+located	O
+in	O
+the	O
+720	O
+-	O
+nucleotide	O
+leader	O
+segment	O
+preceding	O
+the	O
+cpc	B-GENE
+-	I-GENE
+1	I-GENE
+coding	I-GENE
+region	I-GENE
+.	O
+
+The	O
+HOI	O
+induced	O
+a	O
+nearly	O
+fourfold	O
+increase	O
+in	O
+ANF	B-GENE
+in	O
+the	O
+elderly	O
+,	O
+whereas	O
+that	O
+for	O
+the	O
+young	O
+was	O
+threefold	O
+.	O
+
+To	O
+assess	O
+the	O
+ability	O
+of	O
+the	O
+atria	O
+to	O
+maintain	O
+elevated	O
+plasma	O
+concentrations	O
+of	O
+atrial	B-GENE
+natriuretic	I-GENE
+peptide	I-GENE
+(	O
+ANP	B-GENE
+)	O
+,	O
+the	O
+temporal	O
+changes	O
+in	O
+plasma	B-GENE
+ANP	I-GENE
+concentrations	O
+were	O
+studied	O
+in	O
+seven	O
+chloralose	O
+-	O
+anaesthetized	O
+dogs	O
+during	O
+4	O
+h	O
+of	O
+sustained	O
+rapid	O
+cardiac	O
+pacing	O
+.	O
+
+Ig	B-GENE
+D	I-GENE
+-	O
+JH	B-GENE
+recombinations	O
+may	O
+precede	O
+TcR	B-GENE
+gene	I-GENE
+recombination	O
+in	O
+these	O
+early	O
+T	O
+cell	O
+lines	O
+,	O
+and	O
+some	O
+but	O
+not	O
+all	O
+express	O
+sterile	O
+Cmu	B-GENE
+transcripts	I-GENE
+.	O
+
+The	O
+RAD18	B-GENE
+gene	I-GENE
+open	I-GENE
+reading	I-GENE
+frame	I-GENE
+encodes	O
+a	O
+protein	O
+of	O
+487	O
+amino	O
+acids	O
+,	O
+with	O
+a	O
+calculated	O
+molecular	O
+weight	O
+of	O
+55	O
+,	O
+512	O
+.	O
+
+Atomic	O
+absorption	O
+spectrophotometry	O
+applied	O
+to	O
+bacterially	O
+expressed	O
+E1A	B-GENE
+proteins	I-GENE
+revealed	O
+that	O
+the	O
+289	O
+-	O
+amino	O
+acid	O
+protein	O
+binds	O
+one	O
+zinc	O
+ion	O
+,	O
+whereas	O
+the	O
+243	O
+-	O
+amino	O
+acid	O
+protein	O
+binds	O
+no	O
+zinc	O
+.	O
+
+Most	O
+patients	O
+preferred	O
+tablets	O
+to	O
+injection	O
+both	O
+on	O
+day	O
+1	O
+(	O
+313	O
+v	O
+200	O
+)	O
+and	O
+at	O
+follow	O
+up	O
+(	O
+373	O
+v	O
+104	O
+)	O
+.	O
+
+Plots	O
+of	O
+RV	O
+,	O
+LV	O
++	O
+S	O
+and	O
+2A	O
+weight	O
+vs	O
+real	O
+hematocrit	O
+showed	O
+sharp	O
+upward	O
+inflections	O
+at	O
+real	O
+hematocrit	O
+65	O
+%	O
+,	O
+suggesting	O
+a	O
+possible	O
+role	O
+of	O
+increased	O
+viscosity	O
+in	O
+CO	O
+cardiomegaly	O
+at	O
+the	O
+higher	O
+hematocrit	O
+.	O
+
+The	O
+absorbable	O
+perisplenic	O
+mesh	O
+is	O
+an	O
+important	O
+improvement	O
+,	O
+and	O
+in	O
+some	O
+cases	O
+it	O
+may	O
+replace	O
+other	O
+techniques	O
+for	O
+arresting	O
+splenic	O
+bleeding	O
+.	O
+
+A	O
+rare	O
+chronic	O
+course	O
+of	O
+Budd	O
+-	O
+Chiari	O
+syndrome	O
+associated	O
+with	O
+thrombosis	O
+of	O
+the	O
+portal	O
+vein	O
+was	O
+observed	O
+in	O
+a	O
+30	O
+-	O
+year	O
+-	O
+old	O
+male	O
+patient	O
+suffering	O
+from	O
+postmyocarditic	O
+cardiosclerosis	O
+.	O
+
+After	O
+one	O
+accommodation	O
+night	O
+,	O
+sleep	O
+EEG	O
+recordings	O
+were	O
+performed	O
+during	O
+three	O
+consecutive	O
+nights	O
+in	O
+ten	O
+drug	O
+-	O
+free	O
+inpatients	O
+presenting	O
+generalized	O
+anxiety	O
+disorder	O
+(	O
+GAD	O
+)	O
+with	O
+significant	O
+depression	O
+,	O
+compared	O
+with	O
+a	O
+age	O
+-	O
+and	O
+sex	O
+-	O
+matched	O
+group	O
+of	O
+patients	O
+with	O
+GAD	O
+and	O
+a	O
+group	O
+of	O
+primary	O
+major	O
+depressive	O
+disorder	O
+(	O
+MDD	O
+)	O
+patients	O
+.	O
+
+Oligonucleotide	O
+mutagenesis	O
+of	O
+these	O
+binding	O
+domains	O
+indicated	O
+their	O
+importance	O
+in	O
+the	O
+transcriptional	O
+regulation	O
+of	O
+the	O
+E3	B-GENE
+promoter	I-GENE
+in	O
+yeast	O
+cells	O
+.	O
+
+The	O
+concentration	O
+of	O
+PGI2	O
+on	O
+the	O
+newly	O
+-	O
+formed	O
+luminal	O
+surface	O
+remained	O
+low	O
+.	O
+
+Effects	O
+of	O
+single	O
+and	O
+combined	O
+maltose	O
+tetrapalmitate	O
+immunotherapy	O
+,	O
+cyclophosphamide	O
+chemotherapy	O
+and	O
+radiotherapy	O
+on	O
+ethyl	O
+carbamate	O
+accelerated	O
+primary	O
+lung	O
+cancer	O
+in	O
+A	O
+/	O
+J	O
+mice	O
+.	O
+
+D	O
+.	O
+
+Phase	O
+II	O
+study	O
+of	O
+VP	O
+-	O
+16	O
+(	O
+capsule	O
+)	O
+in	O
+solid	O
+tumors	O
+.	O
+
+When	O
+the	O
+coding	O
+segments	O
+,	O
+including	O
+both	O
+framework	O
+and	O
+complementarity	O
+-	O
+determining	O
+regions	O
+,	O
+of	O
+these	O
+genes	O
+and	O
+the	O
+murine	O
+probe	O
+sequences	O
+are	O
+compared	O
+by	O
+metric	O
+analysis	O
+,	O
+it	O
+is	O
+apparent	O
+that	O
+the	O
+caiman	O
+genes	O
+are	O
+only	O
+slightly	O
+more	O
+related	O
+to	O
+each	O
+other	O
+than	O
+to	O
+the	O
+mammalian	O
+sequence	O
+,	O
+consistent	O
+with	O
+significant	O
+preservation	O
+of	O
+nucleotide	O
+sequence	O
+over	O
+an	O
+extended	O
+period	O
+of	O
+phylogenetic	O
+time	O
+.	O
+
+An	O
+unusual	O
+feature	O
+of	O
+these	O
+replicative	O
+genes	O
+is	O
+that	O
+the	O
+smaller	O
+mRNA	O
+begins	O
+within	O
+a	O
+long	O
+open	O
+reading	O
+frame	O
+of	O
+the	O
+larger	O
+mRNA	O
+.	O
+
+Different	O
+sequence	O
+elements	O
+of	O
+both	O
+the	O
+retroviral	O
+vectors	O
+and	O
+the	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+recombined	O
+during	O
+genesis	O
+of	O
+highly	O
+oncogenic	O
+retroviruses	O
+CMII	O
+,	O
+MC29	O
+,	O
+or	O
+MH2	O
+.	O
+
+81	O
+milk	O
+samples	O
+collected	O
+from	O
+35	O
+donors	O
+3	O
+days	O
+to	O
+7	O
+months	O
+after	O
+delivery	O
+were	O
+examined	O
+for	O
+the	O
+occurrence	O
+of	O
+cytomegalovirus	O
+(	O
+CMV	O
+)	O
+.	O
+
+Subcloning	O
+of	O
+DNA	O
+fragments	O
+from	O
+the	O
+8	O
+.	O
+5	O
+-	O
+kilobase	O
+(	O
+kb	O
+)	O
+insert	O
+of	O
+pAVO4	O
+defined	O
+a	O
+4	O
+-	O
+kb	O
+DNA	O
+fragment	O
+which	O
+contained	O
+the	O
+functional	B-GENE
+FBP	I-GENE
++	I-GENE
+gene	I-GENE
+and	O
+its	O
+regulatory	O
+region	O
+.	O
+
+Three	O
+cases	O
+of	O
+primary	O
+signet	O
+-	O
+ring	O
+cell	O
+carcinoma	O
+of	O
+the	O
+rectum	O
+are	O
+described	O
+.	O
+
+The	O
+data	O
+obtained	O
+up	O
+to	O
+now	O
+only	O
+suggest	O
+the	O
+future	O
+potentiality	O
+of	O
+Bestatin	O
+treatment	O
+for	O
+these	O
+types	O
+of	O
+malignancy	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+dopaminergic	O
+regulation	O
+of	O
+adrenal	O
+zona	O
+glomerulosa	O
+corticosteroid	O
+and	O
+renal	B-GENE
+renin	I-GENE
+secretion	O
+is	O
+absent	O
+in	O
+patients	O
+with	O
+high	O
+spinal	O
+cord	O
+transections	O
+,	O
+suggesting	O
+that	O
+intact	O
+neural	O
+pathways	O
+from	O
+the	O
+central	O
+nervous	O
+system	O
+are	O
+necessary	O
+for	O
+metoclopramide	O
+stimulation	O
+of	O
+aldosterone	O
+and	O
+renin	B-GENE
+secretion	O
+in	O
+men	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+enhancer	O
+sequences	O
+,	O
+the	O
+adenovirus	B-GENE
+E1A	I-GENE
+gene	I-GENE
+can	O
+not	O
+stimulate	O
+CATase	B-GENE
+synthesis	O
+.	O
+
+These	O
+IgG	B-GENE
+antibodies	I-GENE
+in	O
+the	O
+babies	O
+diminished	O
+rapidly	O
+after	O
+delivery	O
+,	O
+and	O
+were	O
+detectable	O
+only	O
+in	O
+3	O
+cases	O
+at	O
+2	O
+,	O
+3	O
+,	O
+and	O
+5	O
+months	O
+of	O
+ages	O
+out	O
+of	O
+38	O
+babies	O
+up	O
+to	O
+21	O
+months	O
+.	O
+
+Fine	O
+analysis	O
+at	O
+the	O
+nucleotide	O
+level	O
+of	O
+the	O
+early	O
+events	O
+in	O
+the	O
+digestion	O
+with	O
+nuclease	B-GENE
+S1	I-GENE
+shows	O
+that	O
+the	O
+enzyme	O
+attacks	O
+preferentially	O
+the	O
+sequence	O
+(	O
+G	O
+-	O
+A	O
+)	O
+12	O
+on	O
+the	O
+message	O
+complementary	O
+strand	O
+.	O
+
+Those	O
+dosages	O
+that	O
+inhibited	O
+mean	O
+NTE	B-GENE
+activity	O
+in	O
+spinal	O
+cord	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+72	O
+%	O
+and	O
+brain	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+66	O
+%	O
+of	O
+control	O
+values	O
+within	O
+44	O
+hr	O
+postexposure	O
+produced	O
+marked	O
+spinal	O
+cord	O
+pathology	O
+14	O
+days	O
+postexposure	O
+in	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+90	O
+%	O
+of	O
+similarly	O
+dosed	O
+animals	O
+.	O
+
+FK	O
+33	O
+-	O
+824	O
+,	O
+a	O
+methionine	O
+-	O
+enkephalin	B-GENE
+analogue	O
+,	O
+suppressed	O
+plasma	O
+ACTH	B-GENE
+to	O
+85	O
+%	O
+of	O
+basal	O
+level	O
+,	O
+while	O
+bromocriptine	O
+(	O
+CB	O
+-	O
+154	O
+)	O
+caused	O
+no	O
+significant	O
+change	O
+.	O
+
+A	O
+v	B-GENE
+-	I-GENE
+erbB	I-GENE
+-	I-GENE
+related	I-GENE
+protooncogene	I-GENE
+,	O
+c	B-GENE
+-	I-GENE
+erbB	I-GENE
+-	I-GENE
+2	I-GENE
+,	O
+is	O
+distinct	O
+from	O
+the	O
+c	B-GENE
+-	I-GENE
+erbB	I-GENE
+-	I-GENE
+1	I-GENE
+/	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+receptor	I-GENE
+gene	O
+and	O
+is	O
+amplified	O
+in	O
+a	O
+human	O
+salivary	O
+gland	O
+adenocarcinoma	O
+.	O
+
+The	O
+sequence	O
+analysis	O
+of	O
+both	O
+products	O
+of	O
+individual	O
+phi	O
+80	O
+site	O
+-	O
+specific	O
+recombination	O
+events	O
+in	O
+vivo	O
+shows	O
+that	O
+recombination	O
+with	O
+a	O
+secondary	O
+attachment	O
+(	O
+att	O
+)	O
+site	O
+generates	O
+several	O
+different	O
+novel	O
+joints	O
+at	O
+the	O
+mismatched	O
+position	O
+:	O
+one	O
+recombination	O
+event	O
+resulted	O
+in	O
+a	O
+single	O
+base	O
+-	O
+pair	O
+deletion	O
+and	O
+two	O
+other	O
+recombination	O
+events	O
+resulted	O
+in	O
+two	O
+different	O
+single	O
+base	O
+-	O
+pair	O
+substitutions	O
+.	O
+
+This	O
+L	B-GENE
+-	I-GENE
+myc	I-GENE
+sequence	I-GENE
+is	O
+amplified	O
+10	O
+-	O
+20	O
+-	O
+fold	O
+in	O
+four	O
+SCLC	O
+cell	O
+line	O
+DNAs	O
+and	O
+in	O
+one	O
+SCLC	O
+tumour	O
+specimen	O
+taken	O
+directly	O
+from	O
+a	O
+patient	O
+.	O
+
+Temperature	O
+-	O
+shift	O
+experiments	O
+using	O
+synchronously	O
+grown	O
+cells	O
+of	O
+a	O
+delta	B-GENE
+top1	I-GENE
+top2	B-GENE
+temperature	I-GENE
+-	I-GENE
+sensitive	I-GENE
+(	I-GENE
+ts	I-GENE
+)	I-GENE
+double	I-GENE
+mutant	I-GENE
+and	O
+its	O
+isogenic	O
+top2	B-GENE
+ts	O
+strain	O
+show	O
+that	O
+,	O
+whereas	O
+mitotic	O
+blocks	O
+can	O
+prevent	O
+killing	O
+of	O
+the	O
+top2	B-GENE
+ts	I-GENE
+mutant	I-GENE
+at	O
+a	O
+nonpermissive	O
+temperature	O
+,	O
+the	O
+same	O
+treatments	O
+are	O
+ineffective	O
+in	O
+preventing	O
+cell	O
+death	O
+of	O
+the	O
+delta	B-GENE
+top1	I-GENE
+top2	B-GENE
+ts	I-GENE
+double	I-GENE
+mutant	I-GENE
+.	O
+
+The	O
+homology	O
+to	O
+v	B-GENE
+-	I-GENE
+mil	I-GENE
+starts	O
+within	O
+the	O
+coding	O
+sequence	O
+of	O
+exon	O
+1	O
+and	O
+ends	O
+within	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+of	O
+exon	O
+11	O
+,	O
+12	O
+nucleotides	O
+downstream	O
+from	O
+the	O
+nonsense	O
+codon	O
+terminating	O
+the	O
+large	O
+open	O
+reading	O
+frame	O
+shared	O
+between	O
+c	B-GENE
+-	I-GENE
+mil	I-GENE
+and	O
+v	B-GENE
+-	I-GENE
+mil	I-GENE
+.	O
+
+Examination	O
+of	O
+the	O
+sequence	O
+of	O
+the	O
+Punta	B-GENE
+Toro	I-GENE
+M	I-GENE
+gene	I-GENE
+product	I-GENE
+reveals	O
+the	O
+presence	O
+of	O
+multiple	O
+hydrophobic	O
+sequences	O
+including	O
+a	O
+19	O
+-	O
+amino	O
+acid	O
+,	O
+carboxy	O
+-	O
+proximal	O
+,	O
+hydrophobic	O
+region	O
+(	O
+G2	O
+)	O
+.	O
+
+Six	O
+(	O
+four	O
+FAP	O
+;	O
+two	O
+primary	O
+amyloidosis	O
+)	O
+also	O
+had	O
+diffusely	O
+positive	O
+myocardial	O
+uptakes	O
+,	O
+but	O
+the	O
+intensity	O
+was	O
+less	O
+than	O
+that	O
+of	O
+the	O
+sternum	O
+.	O
+
+The	O
+intensity	O
+of	O
+myocardial	O
+uptake	O
+of	O
+Tc	O
+-	O
+99m	O
+-	O
+PYP	O
+in	O
+patients	O
+with	O
+echocardiographic	O
+left	O
+ventricular	O
+hypertrophy	O
+and	O
+/	O
+or	O
+highly	O
+refractile	O
+myocardial	O
+echoes	O
+,	O
+so	O
+-	O
+called	O
+granular	O
+sparkling	O
+appearance	O
+(	O
+GS	O
+)	O
+was	O
+slightly	O
+greater	O
+than	O
+that	O
+in	O
+patients	O
+with	O
+neither	O
+myocardial	O
+hypertrophy	O
+nor	O
+GS	O
+.	O
+
+Alveolar	O
+lymphocytes	O
+were	O
+surprisingly	O
+increased	O
+in	O
+most	O
+patients	O
+with	O
+AIDS	O
+(	O
+mean	O
+26	O
+.	O
+1	O
++	O
+/	O
+-	O
+21	O
+.	O
+9	O
+%	O
+;	O
+range	O
+1	O
+-	O
+76	O
+%	O
+)	O
+and	O
+CGL	O
+(	O
+mean	O
+26	O
+.	O
+6	O
++	O
+/	O
+-	O
+22	O
+.	O
+6	O
+%	O
+;	O
+range	O
+3	O
+-	O
+76	O
+%	O
+)	O
+with	O
+criteria	O
+of	O
+activation	O
+contrasting	O
+with	O
+the	O
+blood	O
+lymphopenia	O
+.	O
+
+We	O
+have	O
+determined	O
+that	O
+these	O
+nicks	O
+occur	O
+in	O
+both	O
+the	O
+wild	O
+-	O
+type	O
+and	O
+the	O
+mutant	O
+sites	O
+.	O
+
+The	O
+sequence	O
+was	O
+determined	O
+for	O
+a	O
+4024	O
+-	O
+base	O
+pair	O
+(	O
+bp	O
+)	O
+segment	O
+that	O
+extends	O
+from	O
+149	O
+bp	O
+5	O
+'	O
+to	O
+the	O
+cap	O
+site	O
+of	O
+alpha	B-GENE
+1	I-GENE
+to	O
+207	O
+bp	O
+3	O
+'	O
+to	O
+psi	B-GENE
+alpha	I-GENE
+.	O
+
+When	O
+phosphorylation	O
+of	O
+exogenous	O
+peptide	O
+substrates	O
+was	O
+measured	O
+as	O
+a	O
+function	O
+of	O
+receptor	O
+self	O
+-	O
+phosphorylation	O
+,	O
+tyrosine	B-GENE
+kinase	I-GENE
+activity	O
+was	O
+found	O
+to	O
+be	O
+enhanced	O
+two	O
+to	O
+threefold	O
+at	O
+1	O
+-	O
+2	O
+mol	O
+of	O
+phosphate	O
+per	O
+mol	O
+of	O
+receptor	O
+.	O
+
+The	O
+pet56	B-GENE
+and	O
+his3	B-GENE
+genes	I-GENE
+are	O
+transcribed	O
+divergently	O
+from	O
+initiation	O
+sites	O
+that	O
+are	O
+separated	O
+by	O
+only	O
+192	O
+bp	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+in	O
+patients	O
+with	O
+first	O
+-	O
+attack	O
+genital	O
+herpes	O
+,	O
+the	O
+type	O
+of	O
+HSV	O
+is	O
+the	O
+most	O
+important	O
+determinant	O
+of	O
+subsequent	O
+recurrences	O
+and	O
+that	O
+intravenous	O
+acyclovir	O
+has	O
+little	O
+effect	O
+on	O
+subsequent	O
+recurrences	O
+.	O
+
+Comparison	O
+of	O
+sequences	O
+of	O
+ovine	O
+and	O
+bovine	O
+,	O
+rat	O
+and	O
+guinea	B-GENE
+-	I-GENE
+pig	I-GENE
+alpha	I-GENE
+s1	I-GENE
+-	I-GENE
+casein	I-GENE
+mRNAs	I-GENE
+has	O
+revealed	O
+a	O
+greater	O
+homology	O
+in	O
+the	O
+3	O
+'	O
+and	O
+especially	O
+5	O
+'	O
+non	O
+coding	O
+regions	O
+.	O
+
+Comparison	O
+with	O
+a	O
+recently	O
+described	O
+c	B-GENE
+-	I-GENE
+sis	I-GENE
+cDNA	I-GENE
+clone	I-GENE
+(	O
+Collins	O
+et	O
+al	O
+.	O
+,	O
+Nature	O
+316	O
+,	O
+748	O
+-	O
+750	O
+(	O
+1985	O
+)	O
+)	O
+revealed	O
+that	O
+the	O
+1	O
+.	O
+9	O
+kbp	O
+DNA	O
+region	O
+contained	O
+a	O
+large	O
+5	B-GENE
+'	I-GENE
+c	I-GENE
+-	I-GENE
+sis	I-GENE
+exon	I-GENE
+of	O
+at	O
+least	O
+1050	O
+bp	O
+.	O
+
+It	O
+was	O
+also	O
+suggested	O
+that	O
+the	O
+biological	O
+activities	O
+of	O
+5	O
+-	O
+FU	O
+,	O
+ADM	O
+and	O
+MMC	O
+in	O
+FAMLIP	O
+were	O
+stable	O
+in	O
+FULIP	O
+,	O
+ADRLIP	O
+and	O
+MMCLIP	O
+.	O
+
+Surprisingly	O
+,	O
+a	O
+C	O
+to	O
+G	O
+transversion	O
+at	O
+the	O
+first	O
+residue	O
+of	O
+the	O
+CAT	B-GENE
+pentanucleotide	I-GENE
+,	O
+which	O
+severely	O
+impairs	O
+the	O
+activity	O
+of	O
+both	O
+promoters	O
+,	O
+appears	O
+to	O
+increase	O
+affinity	O
+of	O
+the	O
+CAT	B-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+of	O
+3874	O
+bp	O
+of	O
+cloned	O
+R	O
+.	O
+sphaeroides	O
+chromosomal	O
+DNA	O
+,	O
+including	O
+the	O
+three	O
+structural	O
+genes	O
+fbcF	B-GENE
+,	O
+fbcB	B-GENE
+and	O
+fbcC	B-GENE
+has	O
+been	O
+determined	O
+.	O
+
+The	O
+N	O
+-	O
+terminal	O
+sequence	O
+of	O
+one	O
+hydrophilic	O
+peptide	O
+of	O
+the	O
+FeS	B-GENE
+protein	I-GENE
+has	O
+been	O
+also	O
+obtained	O
+confirming	O
+the	O
+fbcF	B-GENE
+reading	O
+frame	O
+.	O
+
+The	O
+5	O
+'	O
+and	O
+3	O
+'	O
+untranslated	O
+sequences	O
+contain	O
+characteristic	O
+sequences	O
+that	O
+are	O
+involved	O
+in	O
+the	O
+initiation	O
+and	O
+termination	O
+of	O
+transcription	O
+,	O
+including	O
+two	O
+possible	O
+promoters	O
+,	O
+one	O
+of	O
+which	O
+may	O
+contain	O
+two	O
+overlapping	O
+-	O
+10	O
+sequences	O
+.	O
+
+Unlike	O
+P135gag	B-GENE
+-	O
+myb	B-GENE
+-	O
+ets	B-GENE
+and	O
+the	O
+Mr	O
+75	O
+,	O
+000	O
+translation	O
+product	O
+of	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+(	O
+P75c	B-GENE
+-	I-GENE
+myb	I-GENE
+)	O
+,	O
+which	O
+are	O
+nuclear	O
+proteins	O
+,	O
+P54c	B-GENE
+-	I-GENE
+ets	I-GENE
+was	O
+found	O
+to	O
+be	O
+predominantly	O
+cytoplasmic	O
+.	O
+
+The	O
+Dox	B-GENE
+-	I-GENE
+A2	I-GENE
+locus	I-GENE
+is	O
+within	O
+3	O
+.	O
+4	O
+to	O
+4	O
+.	O
+4	O
+kb	O
+of	O
+the	O
+Df	B-GENE
+(	I-GENE
+2L	I-GENE
+)	I-GENE
+OD15	I-GENE
+breakpoint	I-GENE
+,	O
+placing	O
+four	O
+of	O
+the	O
+vital	O
+loci	O
+within	O
+a	O
+maximum	O
+of	O
+15	O
+.	O
+5	O
+kb	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+end	O
+of	O
+this	O
+polypeptide	O
+harbors	O
+three	O
+types	O
+of	O
+repeated	O
+sequences	O
+.	O
+
+Further	O
+outbreaks	O
+of	O
+ocular	O
+disease	O
+in	O
+farmed	O
+red	O
+deer	O
+calves	O
+caused	O
+by	O
+HVC	O
+-	O
+1	O
+were	O
+investigated	O
+.	O
+
+From	O
+our	O
+ultrastructural	O
+and	O
+biochemical	O
+studies	O
+,	O
+it	O
+is	O
+evident	O
+that	O
+Type	O
+II	O
+pneumocytes	O
+are	O
+an	O
+early	O
+target	O
+of	O
+radiation	O
+and	O
+the	O
+release	O
+of	O
+surfactant	O
+into	O
+the	O
+alveolus	O
+shortly	O
+after	O
+exposure	O
+persists	O
+for	O
+days	O
+and	O
+weeks	O
+.	O
+
+Thirty	O
+of	O
+the	O
+clones	O
+contained	O
+a	O
+complete	O
+340	O
+base	O
+-	O
+pair	O
+dimer	O
+unit	O
+of	O
+the	O
+repeat	O
+.	O
+
+Two	O
+copies	O
+of	O
+the	O
+72	O
+-	O
+bp	O
+repeat	O
+provided	O
+efficient	O
+activation	O
+of	O
+gene	O
+expression	O
+.	O
+
+The	O
+open	O
+reading	O
+frames	O
+of	O
+rbsD	B-GENE
+,	O
+rbsA	B-GENE
+,	O
+and	O
+rbsC	B-GENE
+encode	O
+proteins	O
+of	O
+139	O
+,	O
+501	O
+,	O
+and	O
+321	O
+amino	O
+acid	O
+residues	O
+,	O
+respectively	O
+.	O
+
+Cattaneo	O
+,	O
+and	O
+J	O
+.	O
+
+Human	B-GENE
+alpha	I-GENE
+-	I-GENE
+galactosidase	I-GENE
+A	I-GENE
+:	O
+nucleotide	O
+sequence	O
+of	O
+a	O
+cDNA	O
+clone	O
+encoding	O
+the	O
+mature	O
+enzyme	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequence	O
+was	O
+determined	O
+to	O
+be	O
+residues	O
+716	O
+-	O
+724	O
+and	O
+hence	O
+lysine	O
+residue	O
+721	O
+is	O
+located	O
+within	O
+the	O
+ATP	O
+-	O
+binding	O
+site	O
+.	O
+
+Osteocalcin	B-GENE
+(	O
+and	O
+urinary	O
+hydroxyproline	O
+)	O
+were	O
+not	O
+elevated	O
+in	O
+isolated	O
+hyperphosphatasaemia	O
+,	O
+indicating	O
+that	O
+mechanisms	O
+other	O
+than	O
+increased	O
+bone	O
+turnover	O
+may	O
+account	O
+for	O
+the	O
+markedly	O
+elevated	O
+serum	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+activity	O
+in	O
+these	O
+subjects	O
+.	O
+
+Analysis	O
+of	O
+glucocorticoid	O
+unresponsive	O
+cell	O
+variants	O
+using	O
+a	O
+mouse	B-GENE
+glucocorticoid	I-GENE
+receptor	I-GENE
+complementary	O
+DNA	O
+clone	O
+.	O
+
+Among	O
+the	O
+v	B-GENE
+-	I-GENE
+myc	I-GENE
+codons	O
+,	O
+the	O
+first	O
+5	O
+are	O
+derived	O
+from	O
+the	O
+noncoding	O
+5	O
+'	O
+terminus	O
+of	O
+the	O
+second	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+exon	O
+,	O
+and	O
+412	O
+codons	O
+correspond	O
+to	O
+the	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+coding	O
+region	O
+.	O
+
+A	O
+recombinant	O
+vector	O
+,	O
+p410	O
++	O
+,	O
+was	O
+constructed	O
+which	O
+carried	O
+the	O
+BamHI	B-GENE
+-	I-GENE
+K	I-GENE
+fragment	I-GENE
+(	O
+nucleotides	O
+107565	O
+to	O
+112625	O
+of	O
+the	O
+B95	O
+-	O
+8	O
+strain	O
+,	O
+encoding	O
+the	O
+EBV	O
+-	O
+associated	O
+nuclear	O
+antigen	O
+EBNA	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+the	O
+cis	O
+-	O
+acting	O
+sequence	O
+from	O
+the	O
+BamHI	B-GENE
+-	I-GENE
+C	I-GENE
+fragment	I-GENE
+,	O
+and	O
+a	O
+dominant	O
+selectable	O
+marker	O
+gene	O
+encoding	O
+G	O
+-	O
+418	O
+resistance	O
+in	O
+animal	O
+cells	O
+.	O
+
+13	O
+men	O
+with	O
+a	O
+history	O
+of	O
+recurrent	O
+genital	O
+herpes	O
+simplex	O
+virus	O
+type	O
+2	O
+(	O
+HSV	O
+-	O
+2	O
+)	O
+infection	O
+were	O
+followed	O
+daily	O
+for	O
+4	O
+weeks	O
+with	O
+samples	O
+taken	O
+from	O
+the	O
+urethra	O
+for	O
+virus	O
+isolation	O
+.	O
+
+Next	O
+,	O
+with	O
+carcinoma	O
+presenting	O
+a	O
+leather	O
+bottle	O
+(	O
+linitis	O
+plastica	O
+type	O
+)	O
+of	O
+the	O
+stomach	O
+itself	O
+,	O
+the	O
+II	O
+c	O
+portion	O
+of	O
+the	O
+stomach	O
+consisted	O
+of	O
+fundic	O
+glands	O
+(	O
+undifferentiated	O
+carcinoma	O
+)	O
+shall	O
+become	O
+the	O
+primary	O
+focus	O
+supporting	O
+Nakamura	O
+'	O
+s	O
+theory	O
+.	O
+
+During	O
+the	O
+biosynthesis	O
+of	O
+all	O
+three	O
+mutant	O
+polypeptides	O
+,	O
+the	O
+signal	O
+peptide	O
+is	O
+efficiently	O
+and	O
+accurately	O
+cleaved	O
+from	O
+the	O
+nascent	O
+protein	O
+,	O
+even	O
+though	O
+in	O
+mutants	O
+X2	O
+and	O
+X3	O
+the	O
+cleavage	O
+site	O
+itself	O
+has	O
+been	O
+altered	O
+.	O
+
+The	O
+hexanucleotide	O
+5	O
+'	O
+-	O
+TGTCCT	O
+-	O
+3	O
+'	O
+,	O
+thought	O
+to	O
+be	O
+important	O
+for	O
+GRE	O
+activity	O
+,	O
+not	O
+only	O
+was	O
+found	O
+in	O
+this	O
+sequence	O
+and	O
+in	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+,	O
+but	O
+also	O
+was	O
+present	O
+twice	O
+in	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+gene	O
+that	O
+did	O
+not	O
+show	O
+specific	O
+receptor	O
+binding	O
+.	O
+
+The	O
+smallest	O
+of	O
+the	O
+mini	O
+-	O
+Mu	O
+elements	O
+is	O
+only	O
+7	O
+.	O
+9	O
+kilobase	O
+pairs	O
+long	O
+,	O
+allowing	O
+the	O
+cloning	O
+of	O
+DNA	O
+fragments	O
+of	O
+up	O
+to	O
+31	O
+.	O
+1	O
+kilobase	O
+pairs	O
+,	O
+and	O
+the	O
+largest	O
+of	O
+them	O
+is	O
+21	O
+.	O
+7	O
+kilobase	O
+pairs	O
+,	O
+requiring	O
+that	O
+clones	O
+carry	O
+insertions	O
+of	O
+less	O
+than	O
+17	O
+.	O
+3	O
+kilobase	O
+pairs	O
+.	O
+
+The	O
+52	O
+-	O
+protein	O
+subunit	O
+of	O
+T4	B-GENE
+DNA	I-GENE
+topoisomerase	I-GENE
+is	O
+homologous	O
+to	O
+the	O
+gyrA	B-GENE
+-	I-GENE
+protein	I-GENE
+of	O
+gyrase	B-GENE
+.	O
+
+The	O
+latent	O
+periods	O
+from	O
+the	O
+antral	O
+exclusion	O
+to	O
+the	O
+occurrence	O
+of	O
+anastomotic	O
+ulcers	O
+after	O
+a	O
+subtotal	O
+gastrectomy	O
+with	O
+Billroth	O
+'	O
+s	O
+type	O
+II	O
+reconstruction	O
+varied	O
+from	O
+a	O
+few	O
+days	O
+to	O
+19	O
+years	O
+,	O
+with	O
+an	O
+average	O
+of	O
+2	O
+.	O
+8	O
+years	O
+.	O
+
+The	O
+nucleosomal	O
+arrays	O
+detected	O
+by	O
+MPE	O
+X	O
+Fe	O
+(	O
+II	O
+)	O
+were	O
+characterized	O
+by	O
+a	O
+considerable	O
+loss	O
+of	O
+detail	O
+and	O
+significantly	O
+enhanced	O
+accessibility	O
+,	O
+the	O
+extent	O
+of	O
+which	O
+probably	O
+reflected	O
+the	O
+relative	O
+transcription	O
+rate	O
+of	O
+each	O
+gene	O
+.	O
+
+The	O
+molecular	O
+weight	O
+of	O
+in	O
+vivo	O
+-	O
+labeled	O
+proteins	O
+was	O
+increased	O
+relative	O
+to	O
+that	O
+of	O
+in	O
+vitro	O
+-	O
+translated	O
+proteins	O
+,	O
+indicating	O
+that	O
+a	O
+posttranslational	O
+modification	O
+had	O
+occurred	O
+.	O
+
+Insertion	O
+of	O
+4	O
+bp	O
+reduced	O
+SV40	B-GENE
+early	I-GENE
+promoter	I-GENE
+-	O
+dependent	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+expression	O
+by	O
+six	O
+-	O
+to	O
+eightfold	O
+.	O
+
+In	O
+the	O
+DNAs	O
+of	O
+all	O
+Ph1	O
+-	O
+positive	O
+chronic	O
+myelocytic	O
+leukemia	O
+patients	O
+studied	O
+to	O
+date	O
+,	O
+a	O
+breakpoint	O
+on	O
+chromosome	O
+22	O
+(	O
+the	O
+Ph1	O
+chromosome	O
+)	O
+can	O
+be	O
+demonstrated	O
+with	O
+a	O
+probe	O
+from	O
+the	O
+bcr	B-GENE
+(	O
+breakpoint	B-GENE
+cluster	I-GENE
+region	I-GENE
+)	O
+.	O
+
+Nuclease	O
+footprinting	O
+revealed	O
+that	O
+purified	O
+glucocorticoid	B-GENE
+receptor	I-GENE
+bound	O
+at	O
+multiple	O
+discrete	O
+sites	O
+within	O
+and	O
+at	O
+the	O
+borders	O
+of	O
+the	O
+tandemly	O
+repeated	O
+sequence	O
+motif	O
+that	O
+defines	O
+Sa	B-GENE
+.	O
+
+The	O
+96	O
+-	O
+bp	O
+insert	O
+contained	O
+a	O
+termination	O
+signal	O
+which	O
+caused	O
+the	O
+premature	O
+termination	O
+of	O
+the	O
+protein	O
+,	O
+leading	O
+to	O
+the	O
+generation	O
+of	O
+a	O
+p53	B-GENE
+product	I-GENE
+9	O
+amino	O
+acids	O
+shorter	O
+than	O
+usual	O
+.	O
+
+All	O
+tumors	O
+proved	O
+histologically	O
+to	O
+be	O
+neuroendocrine	O
+in	O
+origin	O
+.	O
+
+The	O
+coding	O
+region	O
+of	O
+2385	O
+nucleotides	O
+corresponds	O
+to	O
+a	O
+polypeptide	O
+chain	O
+of	O
+795	O
+amino	O
+acids	O
+,	O
+giving	O
+a	O
+molecular	O
+weight	O
+of	O
+91	O
+,	O
+555	O
+for	O
+the	O
+hsp108	B-GENE
+protein	I-GENE
+.	O
+
+Transcriptional	O
+control	O
+signals	O
+of	O
+a	O
+herpes	B-GENE
+simplex	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+late	I-GENE
+(	I-GENE
+gamma	I-GENE
+2	I-GENE
+)	I-GENE
+gene	I-GENE
+lie	O
+within	O
+bases	O
+-	O
+34	O
+to	O
++	O
+124	O
+relative	O
+to	O
+the	O
+5	O
+'	O
+terminus	O
+of	O
+the	O
+mRNA	O
+.	O
+
+A	O
+noncatalytic	O
+domain	O
+conserved	O
+among	O
+cytoplasmic	B-GENE
+protein	I-GENE
+-	I-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+modifies	O
+the	O
+kinase	O
+function	O
+and	O
+transforming	O
+activity	O
+of	O
+Fujinami	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+P130gag	I-GENE
+-	O
+fps	B-GENE
+.	O
+
+Gluzman	O
+,	O
+EMBO	O
+J	O
+.	O
+
+A	O
+single	O
+exon	O
+encodes	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+26	O
+amino	O
+acids	O
+of	O
+the	O
+ssd	B-GENE
+chain	I-GENE
+and	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+of	O
+its	O
+mRNA	O
+,	O
+ending	O
+with	O
+a	O
+poly	O
+(	O
+A	O
+)	O
+-	O
+addition	O
+site	O
+.	O
+
+The	O
+5	O
+'	O
+-	O
+nontranslated	O
+sequences	O
+and	O
+parts	O
+of	O
+the	O
+coding	O
+sequences	O
+of	O
+various	O
+yeast	O
+genes	O
+have	O
+been	O
+cloned	O
+into	O
+representative	O
+lacZ	B-GENE
+fusion	O
+vectors	O
+.	O
+
+Two	O
+activities	O
+of	O
+the	O
+D	B-GENE
+protein	I-GENE
+of	O
+the	O
+miniF	O
+plasmid	O
+have	O
+been	O
+found	O
+.	O
+
+SPECT	O
+examination	O
+of	O
+the	O
+TMJ	O
+using	O
+99m	O
+Tc	O
+-	O
+MDP	O
+was	O
+performed	O
+in	O
+43	O
+patients	O
+with	O
+arthrographically	O
+proven	O
+anterior	O
+dislocation	O
+of	O
+the	O
+disc	O
+and	O
+in	O
+30	O
+normals	O
+.	O
+
+Plasma	B-GENE
+renin	I-GENE
+activity	O
+rose	O
+and	O
+the	O
+plasma	O
+aldosterone	O
+level	O
+fell	O
+after	O
+taking	O
+lisinopril	O
+.	O
+
+The	O
+second	O
+group	O
+of	O
+homologous	O
+elements	O
+is	O
+present	O
+in	O
+the	O
+upstream	O
+region	O
+of	O
+both	O
+genes	O
+.	O
+
+Constitutive	O
+function	O
+of	O
+a	O
+positively	O
+regulated	O
+promoter	O
+reveals	O
+new	O
+sequences	O
+essential	O
+for	O
+activity	O
+.	O
+
+We	O
+inserted	O
+genes	O
+or	O
+gene	O
+segments	O
+,	O
+that	O
+code	O
+for	O
+the	O
+bacterial	B-GENE
+chloramphenicol	I-GENE
+acetyltransferase	I-GENE
+,	O
+the	O
+bacterial	O
+gene	O
+conferring	O
+resistance	O
+against	O
+hygromycin	O
+,	O
+and	O
+the	O
+ORF	O
+E7	B-GENE
+of	O
+the	O
+human	O
+papillomavirus	O
+type	O
+18	O
+into	O
+these	O
+vectors	O
+.	O
+
+By	O
+contrast	O
+,	O
+their	O
+basal	O
+adrenal	O
+androgen	O
+levels	O
+were	O
+significantly	O
+decreased	O
+compared	O
+to	O
+those	O
+in	O
+normal	O
+subjects	O
+on	O
+both	O
+the	O
+day	O
+on	O
+and	O
+the	O
+day	O
+off	O
+prednisone	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Identification	O
+of	O
+p40x	O
+-	O
+responsive	O
+regulatory	O
+sequences	O
+within	O
+the	O
+human	O
+T	O
+-	O
+cell	O
+leukemia	O
+virus	O
+type	O
+I	O
+long	O
+terminal	O
+repeat	O
+.	O
+
+During	O
+pentobarbital	O
+anesthesia	O
+,	O
+the	O
+basal	O
+VO2	O
+was	O
+5	O
+.	O
+26	O
+ml	O
+/	O
+kg	O
+/	O
+min	O
+and	O
+was	O
+increased	O
+by	O
+epinephrine	O
+in	O
+a	O
+dose	O
+dependent	O
+manner	O
+at	O
+plasma	O
+concentrations	O
+between	O
+3	O
+.	O
+9	O
+ng	O
+/	O
+ml	O
+(	O
+VO2	O
+=	O
+5	O
+.	O
+68	O
+ml	O
+/	O
+kg	O
+/	O
+min	O
+)	O
+and	O
+36	O
+.	O
+5	O
+ng	O
+/	O
+ml	O
+(	O
+VO2	O
+=	O
+6	O
+.	O
+47	O
+ml	O
+/	O
+kg	O
+/	O
+min	O
+)	O
+.	O
+
+Oligonucleotide	O
+-	O
+directed	O
+mutagenesis	O
+was	O
+used	O
+to	O
+create	O
+an	O
+NdeI	B-GENE
+restriction	I-GENE
+site	I-GENE
+at	O
+the	O
+natural	O
+ATG	O
+of	O
+the	O
+yeast	O
+R	O
+.	O
+
+ACTH	B-GENE
+release	O
+is	O
+transiently	O
+suppressed	O
+in	O
+some	O
+children	O
+after	O
+exogenous	O
+ACTH	B-GENE
+treatment	O
+.	O
+
+We	O
+previously	O
+showed	O
+that	O
+the	O
+upstream	O
+promoter	O
+element	O
+of	O
+the	O
+yeast	B-GENE
+RP39A	I-GENE
+gene	I-GENE
+consists	O
+of	O
+these	O
+identical	O
+sequence	O
+motifs	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+mammalian	O
+erythroid	O
+alpha	B-GENE
+-	I-GENE
+spectrin	I-GENE
+evolved	O
+by	O
+duplication	O
+and	O
+rapid	O
+divergence	O
+from	O
+an	O
+ancestral	O
+alpha	B-GENE
+-	I-GENE
+fodrin	I-GENE
+-	I-GENE
+like	I-GENE
+gene	I-GENE
+.	O
+
+One	O
+group	O
+of	O
+six	O
+cDNA	O
+clones	O
+was	O
+derived	O
+from	O
+a	O
+2	O
+.	O
+9	O
+-	O
+kilobase	O
+early	O
+transcript	O
+encoded	O
+by	O
+the	O
+IR2	O
+repeat	O
+element	O
+and	O
+showed	O
+restriction	O
+site	O
+polymorphism	O
+for	O
+the	O
+enzyme	B-GENE
+SmaI	I-GENE
+.	O
+
+Combined	O
+immunochemotherapy	O
+with	O
+cyclophosphamide	O
+plus	O
+BCG	O
+gave	O
+a	O
+better	O
+enhancement	O
+of	O
+the	O
+antitumor	O
+effect	O
+of	O
+the	O
+cytostatic	O
+than	O
+that	O
+of	O
+the	O
+combination	O
+of	O
+methotrexate	O
+plus	O
+BCG	O
+and	O
+cyclophosphamide	O
+plus	O
+levamisole	O
+.	O
+
+Indeed	O
+,	O
+A	O
+-	O
+MuLV	O
+pseudotyped	O
+with	O
+some	O
+viruses	O
+,	O
+such	O
+as	O
+the	O
+Moloney	O
+MuLV	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+highly	O
+lymphogenic	O
+,	O
+whereas	O
+A	O
+-	O
+MuLV	O
+pseudotyped	O
+with	O
+other	O
+viruses	O
+,	O
+such	O
+as	O
+the	O
+BALB	O
+/	O
+c	O
+endogenous	O
+N	O
+-	O
+tropic	O
+MuLV	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+devoid	O
+of	O
+lymphogenic	O
+potential	O
+(	O
+N	O
+.	O
+
+The	O
+presence	O
+of	O
+circulating	O
+platelet	O
+aggregates	O
+and	O
+elevated	O
+levels	O
+of	O
+fibrinopeptide	B-GENE
+A	I-GENE
+(	O
+a	O
+cleavage	O
+product	O
+of	O
+fibrin	B-GENE
+)	O
+suggests	O
+that	O
+platelet	O
+activation	O
+and	O
+fibrin	B-GENE
+deposition	O
+may	O
+play	O
+a	O
+role	O
+in	O
+the	O
+pathogenesis	O
+of	O
+this	O
+disorder	O
+.	O
+
+4	O
+.	O
+
+In	O
+general	O
+,	O
+the	O
+values	O
+obtained	O
+by	O
+the	O
+two	O
+methods	O
+were	O
+in	O
+agreement	O
+for	O
+each	O
+species	O
+of	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+and	O
+followed	O
+the	O
+order	O
+:	O
+wild	O
+type	O
+greater	O
+than	O
+Glu24	O
+-	O
+-	O
+-	O
+-	O
+Gly	O
+greater	O
+than	O
+Asp27	O
+-	O
+-	O
+-	O
+-	O
+Gly	O
+much	O
+greater	O
+than	O
+Pro7	O
+-	O
+-	O
+-	O
+-	O
+Thr	O
+greater	O
+than	O
+Tyr29	O
+-	O
+-	O
+-	O
+-	O
+Gly	O
+greater	O
+than	O
+Leu47	O
+-	O
+-	O
+-	O
+-	O
+His	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+suppression	O
+of	O
+elevated	O
+prolactin	B-GENE
+levels	O
+in	O
+progressive	O
+metastatic	O
+breast	O
+cancer	O
+patients	O
+is	O
+not	O
+effective	O
+in	O
+restoring	O
+tumor	O
+sensitivity	O
+to	O
+chemotherapy	O
+.	O
+
+We	O
+report	O
+a	O
+prevalence	O
+study	O
+of	O
+the	O
+best	O
+visual	O
+acuity	O
+in	O
+the	O
+affected	O
+eye	O
+of	O
+100	O
+selected	O
+patients	O
+with	O
+herpetic	O
+keratitis	O
+seen	O
+during	O
+a	O
+two	O
+-	O
+year	O
+period	O
+.	O
+
+We	O
+also	O
+found	O
+an	O
+eIF	B-GENE
+-	I-GENE
+4A	I-GENE
+intronless	O
+retroposon	O
+which	O
+,	O
+when	O
+compared	O
+to	O
+the	O
+cDNA	O
+,	O
+contains	O
+a	O
+single	O
+nucleotide	O
+difference	O
+.	O
+
+After	O
+infection	O
+of	O
+293	O
+cells	O
+(	O
+which	O
+provide	O
+complementary	O
+E1a	B-GENE
+-	O
+E1b	B-GENE
+functions	O
+)	O
+,	O
+both	O
+viruses	O
+directed	O
+equal	O
+amounts	O
+of	O
+P	B-GENE
+/	I-GENE
+C	I-GENE
+-	I-GENE
+specific	I-GENE
+mRNA	I-GENE
+transcription	O
+.	O
+
+This	O
+observation	O
+cannot	O
+be	O
+explained	O
+by	O
+the	O
+scanning	O
+model	O
+for	O
+ribosomal	O
+initiation	O
+and	O
+suggests	O
+that	O
+ribosomes	O
+may	O
+be	O
+binding	O
+directly	O
+at	O
+an	O
+internal	O
+mRNA	O
+site	O
+at	O
+or	O
+near	O
+the	O
+initiator	O
+AUG	O
+codon	O
+for	O
+the	O
+C	B-GENE
+protein	I-GENE
+.	O
+
+In	O
+view	O
+of	O
+these	O
+results	O
+,	O
+simultaneous	O
+pancreas	O
+-	O
+kidney	O
+transplantation	O
+appears	O
+to	O
+be	O
+the	O
+treatment	O
+of	O
+choice	O
+for	O
+Type	O
+I	O
+diabetic	O
+patients	O
+.	O
+
+This	O
+makes	O
+these	O
+compounds	O
+attractive	O
+as	O
+vehicles	O
+for	O
+these	O
+and	O
+other	O
+gases	O
+in	O
+-	O
+vivo	O
+and	O
+in	O
+-	O
+vitro	O
+.	O
+
+DNA	O
+sequencing	O
+of	O
+the	O
+DPM1	B-GENE
+gene	I-GENE
+revealed	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+801	O
+bases	O
+.	O
+
+The	O
+relationship	O
+between	O
+primary	O
+malignant	O
+lymphoma	O
+of	O
+the	O
+thyroid	O
+and	O
+chronic	O
+thyroiditis	O
+is	O
+discussed	O
+.	O
+
+Administration	O
+of	O
+anticoagulants	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+heparin	O
+,	O
+prostaglandin	O
+E1	O
+and	O
+ticlopidine	O
+seems	O
+to	O
+be	O
+effective	O
+in	O
+alleviating	O
+symptoms	O
+and	O
+might	O
+prevent	O
+further	O
+deterioration	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+the	O
+L1	B-GENE
+binding	I-GENE
+site	I-GENE
+of	O
+23S	B-GENE
+rRNA	I-GENE
+in	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+.	O
+
+Animals	O
+may	O
+be	O
+immunized	O
+by	O
+oral	O
+vaccination	O
+,	O
+but	O
+natural	O
+mechanisms	O
+that	O
+also	O
+can	O
+terminate	O
+outbreaks	O
+are	O
+discussed	O
+.	O
+
+Prostacyclin	O
+formation	O
+,	O
+reflected	O
+by	O
+the	O
+excretion	O
+rate	O
+of	O
+its	O
+stable	O
+metabolite	O
+6	O
+-	O
+keto	O
+-	O
+prostaglandin	O
+F1	O
+alpha	O
+,	O
+was	O
+measured	O
+by	O
+means	O
+of	O
+radioimmunoassay	O
+in	O
+4	O
+-	O
+hour	O
+urine	O
+specimens	O
+obtained	O
+during	O
+a	O
+smoking	O
+-	O
+free	O
+period	O
+and	O
+after	O
+participants	O
+had	O
+inhaled	O
+smoke	O
+from	O
+four	O
+high	O
+-	O
+nicotine	O
+cigarettes	O
+.	O
+
+However	O
+,	O
+excretion	O
+of	O
+6	O
+-	O
+keto	O
+-	O
+prostaglandin	O
+F1	O
+alpha	O
+was	O
+further	O
+reduced	O
+in	O
+the	O
+smokers	O
+who	O
+used	O
+oral	O
+contraceptives	O
+(	O
+133	O
++	O
+/	O
+-	O
+20	O
+to	O
+86	O
++	O
+/	O
+-	O
+9	O
+ng	O
+/	O
+gm	O
+of	O
+creatinine	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+in	O
+vitro	O
+activity	O
+of	O
+mecillinam	O
+and	O
+amoxicillin	O
+/	O
+clavulanic	O
+acid	O
+against	O
+Escherichia	O
+coli	O
+strains	O
+producing	O
+beta	B-GENE
+-	I-GENE
+lactamases	I-GENE
+of	O
+the	O
+TEM	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+Oxa	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+chromosomal	O
+type	O
+were	O
+studied	O
+using	O
+the	O
+broth	O
+and	O
+agar	O
+dilution	O
+technique	O
+.	O
+
+GCN4	B-GENE
+encodes	O
+a	O
+transcriptional	O
+activator	O
+of	O
+amino	O
+acid	O
+biosynthetic	O
+genes	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+These	O
+results	O
+imply	O
+that	O
+the	O
+GCN3	B-GENE
+product	I-GENE
+can	O
+promote	O
+either	O
+repression	O
+or	O
+activation	O
+of	O
+GCN4	B-GENE
+expression	O
+depending	O
+on	O
+amino	O
+acid	O
+availability	O
+.	O
+
+The	O
+efficacy	O
+of	O
+these	O
+immunosuppressive	O
+drugs	O
+is	O
+clinical	O
+proven	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+S	O
+.	O
+aureus	O
+peptide	O
+carrying	O
+the	O
+phosphoryl	O
+group	O
+was	O
+found	O
+to	O
+be	O
+Gln	O
+-	O
+Val	O
+-	O
+Val	O
+-	O
+Ser	O
+-	O
+Thr	O
+-	O
+Phe	O
+-	O
+Met	O
+-	O
+Gly	O
+-	O
+Asn	O
+-	O
+Gly	O
+-	O
+Leu	O
+-	O
+Ala	O
+-	O
+Ile	O
+-	O
+Pro	O
+-	O
+His	O
+-	O
+Gly	O
+-	O
+Thr	O
+-	O
+Asp	O
+-	O
+Asp	O
+.	O
+
+These	O
+mutations	O
+alter	O
+two	O
+regions	O
+of	O
+GAL4	B-GENE
+protein	I-GENE
+:	O
+the	O
+DNA	O
+binding	O
+domain	O
+,	O
+and	O
+the	O
+transcription	O
+activation	O
+domain	O
+.	O
+
+The	O
+results	O
+indicated	O
+that	O
+two	O
+genes	O
+(	O
+citA	B-GENE
+and	O
+citB	B-GENE
+)	O
+have	O
+separate	O
+promoters	O
+,	O
+and	O
+the	O
+location	O
+of	O
+the	O
+promoter	O
+for	O
+the	O
+citB	B-GENE
+gene	I-GENE
+in	O
+the	O
+Tn3411	B-GENE
+nucleotide	O
+sequence	O
+was	O
+different	O
+from	O
+that	O
+in	O
+pMS185	O
+.	O
+
+The	O
+rci	B-GENE
+gene	I-GENE
+was	O
+fused	O
+with	O
+lacZ	B-GENE
+and	O
+its	O
+gene	O
+product	O
+was	O
+identified	O
+by	O
+Western	O
+blot	O
+analysis	O
+.	O
+
+Structure	O
+and	O
+regulation	O
+of	O
+a	O
+nuclear	O
+gene	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+that	O
+specifies	O
+MRP13	B-GENE
+,	O
+a	O
+protein	O
+of	O
+the	O
+small	O
+subunit	O
+of	O
+the	O
+mitochondrial	O
+ribosome	O
+.	O
+
+After	O
+a	O
+survey	O
+of	O
+the	O
+anatomical	O
+and	O
+physiological	O
+basis	O
+of	O
+operative	O
+treatment	O
+of	O
+behaviour	O
+disorders	O
+by	O
+stereotactic	O
+lesions	O
+in	O
+the	O
+amygdala	O
+and	O
+the	O
+posterior	O
+medial	O
+hypothalamus	O
+the	O
+author	O
+describes	O
+his	O
+own	O
+experiences	O
+with	O
+603	O
+operations	O
+for	O
+control	O
+of	O
+conservatively	O
+untreatable	O
+aggressiveness	O
+.	O
+
+Although	O
+large	O
+epidemiologic	O
+studies	O
+are	O
+best	O
+able	O
+to	O
+identify	O
+the	O
+relative	O
+contributions	O
+of	O
+specific	O
+risk	O
+factors	O
+while	O
+controlling	O
+for	O
+other	O
+risk	O
+factors	O
+,	O
+new	O
+studies	O
+need	O
+to	O
+focus	O
+on	O
+important	O
+unresolved	O
+questions	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+yeast	O
+and	O
+mammalian	O
+mitochondrial	O
+targeting	O
+sequences	O
+are	O
+similar	O
+but	O
+less	O
+related	O
+than	O
+the	O
+mature	O
+polypeptides	O
+.	O
+
+During	O
+insulin	B-GENE
+infusion	O
+,	O
+a	O
+20	O
+%	O
+dextrose	O
+solution	O
+was	O
+infused	O
+by	O
+a	O
+Biostator	O
+in	O
+order	O
+to	O
+maintain	O
+the	O
+patient	O
+'	O
+s	O
+glycemia	O
+at	O
+90	O
+mg	O
+/	O
+dl	O
+.	O
+
+Amounts	O
+of	O
+glucose	O
+infused	O
+during	O
+the	O
+last	O
+20	O
+min	O
+of	O
+each	O
+2	O
+hour	O
+insulin	B-GENE
+infusion	O
+were	O
+(	O
+at	O
+1	O
+and	O
+10	O
+m	O
+/	O
+kg	O
+/	O
+min	O
+respectively	O
+)	O
+:	O
+before	O
+treatment	O
+(	O
+K	O
++	O
+=	O
+2	O
+.	O
+7	O
+mmol	O
+/	O
+l	O
+)	O
+:	O
+2	O
+.	O
+4	O
+and	O
+8	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+/	O
+min	O
+;	O
+after	O
+spironolactone	O
+(	O
+K	O
++	O
+=	O
+3	O
+.	O
+9	O
+mmol	O
+/	O
+l	O
+)	O
+:	O
+3	O
+.	O
+3	O
+and	O
+15	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+/	O
+min	O
+;	O
+after	O
+indomethacine	O
+(	O
+K	O
++	O
+=	O
+3	O
+.	O
+7	O
+mmol	O
+/	O
+l	O
+)	O
+:	O
+5	O
+and	O
+19	O
+mg	O
+/	O
+kg	O
+/	O
+min	O
+after	O
+stopping	O
+drugs	O
+(	O
+K	O
++	O
+=	O
+2	O
+.	O
+9	O
+mmol	O
+/	O
+l	O
+)	O
+:	O
+2	O
+.	O
+5	O
+and	O
+5	O
+.	O
+3	O
+mg	O
+/	O
+kg	O
+/	O
+min	O
+.	O
+
+Mycobacterium	O
+avium	O
+-	O
+intracellulare	O
+complex	O
+infections	O
+in	O
+the	O
+acquired	O
+immunodeficiency	O
+syndrome	O
+.	O
+
+Recurrence	O
+of	O
+oxalate	O
+deposition	O
+in	O
+a	O
+renal	O
+transplant	O
+during	O
+ciclosporin	O
+A	O
+therapy	O
+.	O
+
+The	O
+bile	O
+acid	O
+sequestrants	O
+(	O
+cholestyramine	O
+and	O
+colestipol	O
+)	O
+,	O
+nicotinic	O
+acid	O
+,	O
+fenofibrate	O
+and	O
+inhibitors	O
+of	O
+hydroxymethylglutaryl	B-GENE
+coenzyme	I-GENE
+A	I-GENE
+(	I-GENE
+HMG	I-GENE
+CoA	I-GENE
+)	I-GENE
+reductase	I-GENE
+(	O
+e	O
+.	O
+g	O
+.	O
+lovastatin	O
+or	O
+simvastatin	O
+)	O
+are	O
+the	O
+most	O
+effective	O
+drugs	O
+for	O
+use	O
+in	O
+patients	O
+with	O
+primary	O
+hypercholesterolaemia	O
+;	O
+these	O
+agents	O
+reduce	O
+plasma	O
+concentrations	O
+of	O
+total	O
+and	O
+LDL	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+by	O
+15	O
+to	O
+45	O
+%	O
+.	O
+
+Finally	O
+,	O
+the	O
+pathophysiological	O
+aspects	O
+of	O
+urinary	O
+acidification	O
+are	O
+discussed	O
+,	O
+focusing	O
+on	O
+renal	O
+tubular	O
+acidosis	O
+models	O
+(	O
+induced	O
+by	O
+maleate	O
+and	O
+amphotericin	O
+B	O
+treatment	O
+)	O
+and	O
+their	O
+cellular	O
+mechanisms	O
+,	O
+as	O
+well	O
+as	O
+the	O
+role	O
+of	O
+adrenal	O
+steroids	O
+in	O
+urinary	O
+acidification	O
+.	O
+
+Analysis	O
+in	O
+3	O
+groups	O
+of	O
+patients	O
+suffering	O
+from	O
+simple	O
+acute	O
+and	O
+pernicious	O
+malarial	O
+flare	O
+-	O
+ups	O
+
+Statement	O
+on	O
+the	O
+development	O
+of	O
+guidelines	O
+for	O
+the	O
+prevention	O
+of	O
+AIDS	O
+transmission	O
+in	O
+the	O
+workplace	O
+.	O
+
+Modifications	O
+of	O
+the	O
+involuntary	O
+postcontraction	O
+in	O
+diseased	O
+people	O
+.	O
+
+Cocaine	O
+-	O
+treated	O
+rats	O
+acquired	O
+a	O
+preference	O
+for	O
+cocaine	O
+-	O
+associated	O
+contextual	O
+stimuli	O
+(	O
+CS	O
+)	O
+relative	O
+to	O
+saline	O
+-	O
+injected	O
+control	O
+rats	O
+.	O
+
+Under	O
+these	O
+schedules	O
+,	O
+a	O
+reinforced	O
+response	O
+run	O
+consisted	O
+of	O
+responding	O
+between	O
+eight	O
+and	O
+12	O
+times	O
+on	O
+one	O
+response	O
+key	O
+(	O
+work	O
+key	O
+)	O
+and	O
+then	O
+responding	O
+once	O
+on	O
+a	O
+second	O
+response	O
+key	O
+(	O
+reinforced	O
+key	O
+)	O
+.	O
+
+Intravenous	O
+glucose	O
+tolerance	O
+tests	O
+were	O
+performed	O
+before	O
+operation	O
+,	O
+before	O
+starting	O
+CyA	O
+and	O
+after	O
+3	O
+weeks	O
+.	O
+
+The	O
+effects	O
+of	O
+glutaraldehyde	O
+on	O
+dimensions	O
+and	O
+ultrastructure	O
+of	O
+microvascular	O
+beds	O
+in	O
+rat	O
+mesentery	O
+were	O
+studied	O
+in	O
+two	O
+kinds	O
+of	O
+experiment	O
+,	O
+administering	O
+the	O
+fixative	O
+by	O
+intra	O
+-	O
+arterial	O
+perfusion	O
+at	O
+a	O
+pressure	O
+of	O
+80	O
+mm	O
+Hg	O
+and	O
+by	O
+superfusion	O
+of	O
+the	O
+exteriorized	O
+mesenteric	O
+membrane	O
+.	O
+
+This	O
+gave	O
+rise	O
+to	O
+RNA	O
+molecules	O
+with	O
+3	O
+'	O
+-	O
+untranslated	O
+regions	O
+of	O
+roughly	O
+375	O
+,	O
+655	O
+,	O
+and	O
+945	O
+base	O
+pairs	O
+.	O
+
+Also	O
+,	O
+the	O
+BALB	B-GENE
+/	I-GENE
+c	I-GENE
+gene	I-GENE
+contains	O
+a	O
+single	O
+substitution	O
+in	O
+a	O
+conserved	O
+octamer	O
+sequence	O
+approximately	O
+equal	O
+to	O
+100	O
+nucleotides	O
+upstream	O
+of	O
+the	O
+coding	O
+region	O
+,	O
+which	O
+could	O
+affect	O
+its	O
+expression	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+it	O
+may	O
+be	O
+possible	O
+to	O
+individualize	O
+hCG	B-GENE
+administration	O
+at	O
+midcycle	O
+by	O
+determining	O
+the	O
+number	O
+of	O
+follicles	O
+greater	O
+than	O
+1	O
+cm	O
+by	O
+ultrasound	O
+on	O
+cycle	O
+day	O
+12	O
+or	O
+13	O
+and	O
+giving	O
+hCG	B-GENE
+when	O
+serum	O
+E2	O
+levels	O
+reach	O
+1100	O
+to	O
+1200	O
+pmol	O
+/	O
+l	O
+per	O
+follicle	O
+.	O
+
+Within	O
+Stage	O
+IA	O
+,	O
+141	O
+patients	O
+had	O
+well	O
+differentiated	O
+tumor	O
+(	O
+G1	O
+)	O
+,	O
+20	O
+had	O
+moderately	O
+well	O
+differentiated	O
+tumor	O
+(	O
+G2	O
+)	O
+,	O
+and	O
+12	O
+patients	O
+had	O
+poorly	O
+differentiated	O
+(	O
+G3	O
+)	O
+.	O
+
+Mechanism	O
+of	O
+the	O
+t	O
+(	O
+14	O
+;	O
+18	O
+)	O
+chromosomal	O
+translocation	O
+:	O
+structural	O
+analysis	O
+of	O
+both	O
+derivative	O
+14	O
+and	O
+18	O
+reciprocal	O
+partners	O
+.	O
+
+After	O
+age	O
+30	O
+,	O
+mean	O
+hemoglobin	B-GENE
+levels	O
+for	O
+men	O
+gradually	O
+declined	O
+,	O
+while	O
+those	O
+in	O
+women	O
+rose	O
+,	O
+so	O
+that	O
+the	O
+sex	O
+difference	O
+diminished	O
+after	O
+60	O
+years	O
+of	O
+age	O
+.	O
+
+Ritanserin	O
+is	O
+a	O
+new	O
+substance	O
+with	O
+highly	O
+selective	O
+blocking	O
+activity	O
+on	O
+S2	B-GENE
+receptors	I-GENE
+for	O
+5	O
+-	O
+HT	O
+in	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Ethylene	O
+glycol	O
+and	O
+diethylene	O
+glycol	O
+were	O
+each	O
+administered	O
+once	O
+weekly	O
+subcutaneously	O
+to	O
+groups	O
+of	O
+100	O
+female	O
+NMRI	O
+mice	O
+at	O
+3	O
+dosages	O
+(	O
+30	O
+;	O
+10	O
+und	O
+3	O
+mg	O
+single	O
+dose	O
+per	O
+mouse	O
+)	O
+.	O
+
+Research	O
+on	O
+ethylene	O
+glycol	O
+and	O
+diethylene	O
+glycol	O
+for	O
+carcinogenic	O
+effects	O
+
+The	O
+results	O
+suggest	O
+that	O
+the	O
+greater	O
+estrogenic	O
+influence	O
+associated	O
+with	O
+the	O
+ethinyl	O
+estradiol	O
+-	O
+containing	O
+OC	O
+resulted	O
+in	O
+inhibition	O
+of	O
+coronary	O
+artery	O
+atherosclerosis	O
+despite	O
+a	O
+pronounced	O
+progestin	O
+-	O
+induced	O
+lowering	O
+of	O
+plasma	O
+HDL	B-GENE
+cholesterol	I-GENE
+concentration	O
+and	O
+,	O
+further	O
+,	O
+that	O
+hormonal	O
+balance	O
+may	O
+have	O
+a	O
+marked	O
+influence	O
+on	O
+the	O
+relationship	O
+between	O
+plasma	O
+lipids	O
+and	O
+atherogenesis	O
+.	O
+
+During	O
+BH	O
+the	O
+ventilator	O
+was	O
+disconnected	O
+and	O
+a	O
+bias	O
+flow	O
+of	O
+50	O
+%	O
+O2	O
+at	O
+4	O
+-	O
+5	O
+l	O
+/	O
+min	O
+was	O
+delivered	O
+through	O
+the	O
+side	O
+ports	O
+of	O
+a	O
+small	O
+catheter	O
+whose	O
+tip	O
+was	O
+positioned	O
+1	O
+cm	O
+cephalad	O
+of	O
+the	O
+carina	O
+.	O
+
+Comparison	O
+of	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+removal	O
+using	O
+the	O
+same	O
+polysulphone	O
+membrane	O
+for	O
+haemodialysis	O
+and	O
+haemofiltration	O
+shows	O
+that	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+is	O
+more	O
+effectively	O
+removed	O
+by	O
+convection	O
+than	O
+by	O
+diffusion	O
+when	O
+both	O
+treatment	O
+modes	O
+are	O
+matched	O
+for	O
+blood	O
+flow	O
+and	O
+urea	O
+clearance	O
+.	O
+
+40	O
+.	O
+3	O
++	O
+/	O
+-	O
+10	O
+.	O
+1	O
+mg	O
+/	O
+l	O
+(	O
+SD	O
+)	O
+vs	O
+31	O
+.	O
+2	O
++	O
+/	O
+-	O
+8	O
+.	O
+0	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+beta	B-GENE
+2m	I-GENE
+was	O
+not	O
+significantly	O
+higher	O
+in	O
+patients	O
+with	O
+bone	O
+cysts	O
+(	O
+37	O
+.	O
+7	O
++	O
+/	O
+-	O
+11	O
+.	O
+4	O
+mg	O
+/	O
+l	O
+vs	O
+37	O
+.	O
+0	O
++	O
+/	O
+-	O
+10	O
+.	O
+0	O
+)	O
+,	O
+but	O
+median	O
+duration	O
+of	O
+dialysis	O
+was	O
+significantly	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+longer	O
+in	O
+patients	O
+with	O
+bone	O
+cysts	O
+(	O
+90	O
+vs	O
+57	O
+months	O
+)	O
+.	O
+beta	B-GENE
+2m	I-GENE
+was	O
+lower	O
+in	O
+patients	O
+maintained	O
+on	O
+dialysis	O
+for	O
+less	O
+than	O
+1	O
+year	O
+and	O
+whose	O
+residual	O
+urine	O
+volume	O
+was	O
+greater	O
+than	O
+0	O
+.	O
+1	O
+litre	O
+per	O
+day	O
+.	O
+
+The	O
+mean	O
+percentage	O
+of	O
+linoleic	O
+acid	O
+in	O
+the	O
+triglycerides	O
+of	O
+the	O
+subcutaneous	O
+adipose	O
+tissue	O
+(	O
+PLASAT	O
+)	O
+of	O
+these	O
+subjects	O
+was	O
+substantially	O
+higher	O
+than	O
+that	O
+in	O
+a	O
+similar	O
+group	O
+examined	O
+in	O
+1975	O
+-	O
+1976	O
+.	O
+
+In	O
+overdoses	O
+up	O
+to	O
+2	O
+g	O
+fluvoxamine	O
+no	O
+lasting	O
+toxic	O
+effects	O
+were	O
+observed	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+the	O
+plasma	B-GENE
+prolactin	I-GENE
+response	O
+to	O
+12	O
+.	O
+5	O
+micrograms	O
+i	O
+.	O
+v	O
+.	O
+
+The	O
+remaining	O
+six	O
+patients	O
+had	O
+slightly	O
+decreased	O
+(	O
+n	O
+=	O
+3	O
+)	O
+or	O
+normal	O
+(	O
+n	O
+=	O
+3	O
+)	O
+seminal	O
+parameters	O
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+wild	O
+-	O
+type	O
+strain	O
+containing	O
+a	O
+temperature	B-GENE
+-	I-GENE
+sensitive	I-GENE
+threonyl	I-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+mutation	I-GENE
+showed	O
+increased	O
+thr	B-GENE
+operon	I-GENE
+expression	O
+at	O
+the	O
+non	O
+-	O
+permissive	O
+temperature	O
+,	O
+whereas	O
+none	O
+of	O
+the	O
+mutants	O
+showed	O
+any	O
+change	O
+.	O
+
+Significant	O
+treatment	O
+-	O
+related	O
+problems	O
+appeared	O
+during	O
+the	O
+second	O
+decade	O
+in	O
+5	O
+patients	O
+,	O
+including	O
+one	O
+chest	O
+wall	O
+sarcoma	O
+;	O
+all	O
+of	O
+these	O
+patients	O
+had	O
+received	O
+at	O
+least	O
+60	O
+Gy	O
+to	O
+breast	O
+and	O
+regional	O
+nodal	O
+areas	O
+.	O
+
+Of	O
+7	O
+patients	O
+treated	O
+with	O
+cyclophosphamide	O
+,	O
+hexamethylmelamine	O
+,	O
+adriamycin	O
+and	O
+cisplatin	O
+(	O
+CHAP	O
+-	O
+5	O
+)	O
+,	O
+6	O
+had	O
+measurable	O
+disease	O
+,	O
+of	O
+whom	O
+5	O
+yielded	O
+a	O
+response	O
+(	O
+2	O
+complete	O
+responses	O
+for	O
+19	O
++	O
+and	O
+40	O
+months	O
+and	O
+3	O
+partial	O
+responses	O
+for	O
+4	O
+,	O
+7	O
+and	O
+8	O
+months	O
+)	O
+.	O
+
+Isolation	O
+and	O
+characterization	O
+of	O
+a	O
+vinculin	B-GENE
+cDNA	I-GENE
+from	I-GENE
+chick	I-GENE
+-	I-GENE
+embryo	I-GENE
+fibroblasts	I-GENE
+.	O
+
+A	O
+complementary	O
+study	O
+,	O
+showing	O
+a	O
+good	O
+agreement	O
+between	O
+surface	O
+and	O
+oesophageal	O
+EMGd	O
+seems	O
+to	O
+confirm	O
+that	O
+surface	O
+EMGd	O
+is	O
+a	O
+useful	O
+and	O
+promising	O
+tool	O
+for	O
+clinical	O
+investigation	O
+.	O
+
+No	O
+differences	O
+in	O
+fixation	O
+quality	O
+were	O
+observed	O
+between	O
+cochleas	O
+fixed	O
+by	O
+intravascular	O
+perfusion	O
+and	O
+cochleas	O
+fixed	O
+by	O
+intralabyrinthine	O
+perfusion	O
+.	O
+
+The	O
+DNA	O
+sequence	O
+encodes	O
+a	O
+protein	O
+of	O
+1520	O
+amino	O
+acids	O
+with	O
+sequence	O
+homology	O
+to	O
+the	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+abl	I-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+product	I-GENE
+,	O
+beginning	O
+at	O
+the	O
+amino	O
+terminus	O
+and	O
+extending	O
+656	O
+amino	O
+acids	O
+through	O
+the	O
+region	O
+essential	O
+for	O
+tyrosine	B-GENE
+kinase	I-GENE
+activity	O
+.	O
+
+The	O
+requirement	O
+of	O
+different	O
+essential	O
+fatty	O
+acids	O
+in	O
+patients	O
+with	O
+total	O
+parenteral	O
+nutrition	O
+after	O
+heavy	O
+injury	O
+is	O
+of	O
+special	O
+interest	O
+with	O
+respect	O
+to	O
+the	O
+development	O
+and	O
+prognosis	O
+of	O
+shock	O
+,	O
+sepsis	O
+or	O
+adult	O
+respiratory	O
+distress	O
+syndrome	O
+.	O
+
+The	O
+Drosophila	B-GENE
+melanogaster	I-GENE
+Gart	I-GENE
+gene	I-GENE
+encodes	O
+three	O
+enzymatic	O
+activities	O
+in	O
+the	O
+pathway	O
+for	O
+purine	O
+de	O
+novo	O
+synthesis	O
+.	O
+
+The	O
+role	O
+of	O
+neuroplasticity	O
+in	O
+the	O
+response	O
+to	O
+drugs	O
+.	O
+
+Biol	O
+.	O
+
+The	O
+heart	O
+rate	O
+,	O
+respiratory	O
+rate	O
+,	O
+arterial	O
+O2	O
+and	O
+systemic	O
+vascular	O
+resistance	O
+were	O
+not	O
+significantly	O
+altered	O
+.	O
+
+Human	B-GENE
+rIL	I-GENE
+-	I-GENE
+3	I-GENE
+expressed	O
+in	O
+COS7	O
+cells	O
+has	O
+multipotential	O
+CSF	B-GENE
+activity	O
+in	O
+semisolid	O
+cultures	O
+of	O
+bone	O
+marrow	O
+cells	O
+,	O
+and	O
+selectively	O
+induced	O
+the	O
+proliferation	O
+of	O
+My	O
+-	O
+10	O
++	O
+marrow	O
+or	O
+cord	O
+blood	O
+cells	O
+in	O
+liquid	O
+cultures	O
+.	O
+
+In	O
+14	O
+patients	O
+whose	O
+PaCO2	O
+was	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+39	O
+torr	O
+(	O
+range	O
+39	O
+to	O
+58	O
+torr	O
+)	O
+and	O
+clinical	O
+asthma	O
+score	O
+was	O
+6	O
+or	O
+greater	O
+,	O
+PaCO2	O
+decreased	O
+a	O
+mean	O
+of	O
+11	O
+.	O
+7	O
+torr	O
+during	O
+a	O
+mean	O
+of	O
+8	O
+.	O
+1	O
+hours	O
+.	O
+
+A	O
+randomized	O
+,	O
+prospective	O
+study	O
+was	O
+conducted	O
+to	O
+compare	O
+ovarian	O
+stimulation	O
+with	O
+human	B-GENE
+menopausal	I-GENE
+gonadotropin	I-GENE
+(	O
+hMG	B-GENE
+)	O
+and	O
+human	B-GENE
+follicle	I-GENE
+-	I-GENE
+stimulating	I-GENE
+hormone	I-GENE
+(	O
+hFSH	B-GENE
+)	O
+in	O
+an	O
+in	O
+vitro	O
+fertilization	O
+and	O
+embryo	O
+transfer	O
+(	O
+IVF	O
+-	O
+ET	O
+)	O
+program	O
+.	O
+
+Our	O
+findings	O
+suggest	O
+that	O
+the	O
+mtr	B-GENE
+product	I-GENE
+causes	O
+both	O
+transcription	O
+attenuation	O
+and	O
+inhibition	O
+of	O
+translation	O
+of	O
+trpE	B-GENE
+mRNA	I-GENE
+.	O
+
+Apropos	O
+of	O
+a	O
+case	O
+
+A	O
+prostaglandin	O
+analogue	O
+given	O
+in	O
+early	O
+pregnancy	O
+and	O
+human	B-GENE
+chorionic	I-GENE
+gonadotropin	I-GENE
+given	O
+near	O
+the	O
+end	O
+of	O
+the	O
+ensuing	O
+follicular	O
+phase	O
+were	O
+used	O
+for	O
+controlling	O
+the	O
+reproductive	O
+cycle	O
+,	O
+timing	O
+oocyte	O
+collection	O
+,	O
+and	O
+synchronizing	O
+the	O
+cycles	O
+of	O
+oocyte	O
+donors	O
+and	O
+embryo	O
+recipients	O
+.	O
+
+The	O
+nucleolin	B-GENE
+gene	I-GENE
+extends	O
+over	O
+9000	O
+base	O
+-	O
+pairs	O
+and	O
+is	O
+split	O
+into	O
+14	O
+exons	O
+that	O
+encode	O
+the	O
+706	O
+amino	O
+acid	O
+residues	O
+of	O
+the	O
+protein	O
+.	O
+
+Although	O
+L	O
+-	O
+threo	O
+-	O
+dihydroxyphenylserine	O
+(	O
+DOPS	O
+)	O
+,	O
+an	O
+artificial	O
+norepinephrine	O
+(	O
+NE	O
+)	O
+precursor	O
+,	O
+did	O
+not	O
+change	O
+immobility	O
+in	O
+intact	O
+mice	O
+,	O
+DOPS	O
+significantly	O
+reduced	O
+immobility	O
+in	O
+mice	O
+pretreated	O
+with	O
+the	O
+selective	O
+NE	O
+neurotoxin	O
+DSP4	O
+.	O
+
+Substantial	O
+amounts	O
+of	O
+liposomal	O
+ampicillin	O
+were	O
+recovered	O
+from	O
+isolated	O
+Kupffer	O
+cells	O
+,	O
+the	O
+target	O
+cells	O
+of	O
+L	O
+.	O
+monocytogenes	O
+after	O
+intravenous	O
+inoculation	O
+.	O
+
+This	O
+suggested	O
+that	O
+delta	O
+6	O
+and	O
+delta	O
+5	O
+desaturation	O
+activities	O
+are	O
+normal	O
+in	O
+these	O
+conditions	O
+with	O
+this	O
+C18	O
+:	O
+2w6	O
+supply	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+complete	O
+6	O
+-	O
+kilobase	O
+cDNA	O
+sequence	O
+coding	O
+for	O
+a	O
+chain	O
+of	O
+1775	O
+amino	O
+acids	O
+,	O
+as	O
+well	O
+as	O
+the	O
+genomic	O
+structure	O
+.	O
+
+HDL	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+(	O
++	O
+6	O
+%	O
+,	O
+P	O
+less	O
+than	O
+.	O
+01	O
+)	O
+and	O
+apolipoprotein	B-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+(	O
++	O
+6	O
+%	O
+,	O
+P	O
+less	O
+than	O
+.	O
+01	O
+)	O
+concentrations	O
+increased	O
+significantly	O
+only	O
+in	O
+the	O
+young	O
+.	O
+
+The	O
+Euglena	B-GENE
+ribosomal	I-GENE
+protein	I-GENE
+gene	I-GENE
+cluster	I-GENE
+resembles	O
+the	O
+S	B-GENE
+-	I-GENE
+10	I-GENE
+ribosomal	I-GENE
+protein	I-GENE
+operon	I-GENE
+of	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+in	O
+gene	O
+organization	O
+and	O
+follows	O
+the	O
+exact	O
+linear	O
+order	O
+of	O
+the	O
+analogous	O
+genes	O
+in	O
+the	O
+tobacco	O
+and	O
+liverwort	O
+chloroplast	O
+genomes	O
+.	O
+
+The	O
+distribution	O
+of	O
+the	O
+sites	O
+of	O
+recombinational	O
+resolution	O
+is	O
+inversely	O
+correlated	O
+with	O
+that	O
+of	O
+the	O
+gradient	O
+of	O
+sequence	O
+divergence	O
+,	O
+with	O
+only	O
+approximately	O
+7	O
+%	O
+of	O
+the	O
+X	O
+recombinants	O
+resolved	O
+within	O
+the	O
+3	O
+'	O
+third	O
+of	O
+the	O
+X	O
+blocks	O
+where	O
+two	O
+diverged	O
+Alu	B-GENE
+family	O
+repeats	O
+reside	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+region	O
+upstream	O
+from	O
+M	B-GENE
+.	I-GENE
+voltae	I-GENE
+ORFtrpA	I-GENE
+was	O
+determined	O
+and	O
+revealed	O
+the	O
+presence	O
+of	O
+an	O
+ORF	O
+of	O
+1227	O
+nucleotides	O
+(	O
+ORFtrpB	B-GENE
+)	O
+encoding	O
+a	O
+409	O
+amino	O
+acid	O
+polypeptide	O
+of	O
+mol	O
+.	O
+wt	O
+.	O
+
+Of	O
+49	O
+receptors	O
+which	O
+fired	O
+in	O
+phase	O
+with	O
+ventilation	O
+,	O
+13	O
+behaved	O
+like	O
+mammalian	O
+rapidly	O
+adapting	O
+pulmonary	O
+stretch	O
+receptors	O
+,	O
+19	O
+like	O
+mammalian	O
+slowly	O
+adapting	O
+pulmonary	O
+stretch	O
+receptors	O
+(	O
+PSR	O
+)	O
+,	O
+and	O
+17	O
+like	O
+avian	O
+intrapulmonary	O
+CO2	O
+-	O
+sensitive	O
+chemoreceptors	O
+(	O
+IPC	O
+)	O
+.	O
+
+Symptomatic	O
+hyperventilators	O
+had	O
+a	O
+larger	O
+number	O
+of	O
+sighs	O
+and	O
+abnormally	O
+wide	O
+fluctuations	O
+in	O
+baseline	O
+for	O
+inspiratory	O
+time	O
+,	O
+expiratory	O
+time	O
+,	O
+and	O
+PETCO2	O
+.	O
+
+In	O
+the	O
+IA	O
+task	O
+,	O
+post	O
+-	O
+training	O
+intraperitoneal	O
+injections	O
+of	O
+picrotoxin	O
+and	O
+bicuculline	O
+induced	O
+a	O
+dose	O
+-	O
+dependent	O
+enhancement	O
+of	O
+retention	O
+measured	O
+24	O
+h	O
+after	O
+the	O
+training	O
+,	O
+while	O
+retention	O
+was	O
+not	O
+affected	O
+by	O
+bicuculline	O
+methiodide	O
+(	O
+a	O
+GABA	B-GENE
+receptor	I-GENE
+antagonist	O
+that	O
+does	O
+not	O
+readily	O
+cross	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+)	O
+.	O
+
+Clinical	O
+research	O
+of	O
+non	O
+-	O
+A	O
+,	O
+non	O
+-	O
+B	O
+post	O
+-	O
+transfusion	O
+hepatitis	O
+
+It	O
+is	O
+suggested	O
+that	O
+the	O
+use	O
+of	O
+endogenous	O
+creatinine	O
+clearance	O
+to	O
+estimate	O
+the	O
+glomerular	O
+filtration	O
+rate	O
+(	O
+GFR	O
+)	O
+requires	O
+caution	O
+and	O
+the	O
+recognition	O
+of	O
+the	O
+limitations	O
+of	O
+the	O
+method	O
+,	O
+and	O
+that	O
+simpler	O
+techniques	O
+(	O
+serum	O
+creatinine	O
+or	O
+estimated	O
+endogenous	O
+creatinine	O
+clearance	O
+)	O
+are	O
+preferable	O
+in	O
+routine	O
+practice	O
+.	O
+
+The	O
+protein	O
+mixtures	O
+of	O
+sesame	O
+flour	O
+and	O
+soybean	O
+flour	O
+were	O
+well	O
+accepted	O
+.	O
+
+The	O
+5	O
+'	O
+end	O
+of	O
+the	O
+coding	O
+region	O
+was	O
+located	O
+precisely	O
+by	O
+comparing	O
+the	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+to	O
+the	O
+actual	O
+N	O
+-	O
+terminal	O
+amino	O
+acid	O
+sequence	O
+of	O
+IHF	B-GENE
+.	O
+
+A	O
+protein	O
+footprint	O
+also	O
+was	O
+identified	O
+for	O
+a	O
+GC	O
+box	O
+element	O
+at	O
+nucleotides	O
+-	O
+59	O
+to	O
+-	O
+45	O
+.	O
+
+Insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+II	I-GENE
+(	O
+IGFII	B-GENE
+)	O
+is	O
+a	O
+mitogenic	O
+polypeptide	O
+,	O
+the	O
+mRNAs	O
+of	O
+which	O
+are	O
+present	O
+in	O
+multiple	O
+forms	O
+,	O
+despite	O
+derivation	O
+from	O
+a	O
+single	O
+gene	O
+.	O
+
+The	O
+central	O
+visual	O
+fields	O
+of	O
+2165	O
+normal	O
+and	O
+106	O
+glaucoma	O
+eyes	O
+were	O
+measured	O
+using	O
+a	O
+threshold	O
+related	O
+suprathreshold	O
+strategy	O
+.	O
+
+Effect	O
+of	O
+chronic	O
+undernutrition	O
+on	O
+susceptibility	O
+to	O
+cold	O
+stress	O
+in	O
+young	O
+adult	O
+and	O
+aged	O
+rats	O
+.	O
+
+This	O
+effect	O
+and	O
+the	O
+fact	O
+that	O
+all	O
+three	O
+doses	O
+were	O
+toxic	O
+to	O
+the	O
+dams	O
+dictated	O
+that	O
+a	O
+second	O
+experiment	O
+be	O
+carried	O
+out	O
+at	O
+lower	O
+doses	O
+.	O
+
+The	O
+CHARGE	O
+association	O
+is	O
+a	O
+collection	O
+of	O
+multisystem	O
+congenital	O
+anomalies	O
+including	O
+choanal	O
+atresia	O
+.	O
+
+Esophageal	O
+brush	O
+cytological	O
+screening	O
+was	O
+undertaken	O
+and	O
+blood	O
+concentrations	O
+of	O
+micronutrients	O
+(	O
+vitamin	O
+A	O
+,	O
+E	O
+,	O
+B12	O
+,	O
+folic	O
+acid	O
+and	O
+methionine	O
+)	O
+determined	O
+from	O
+adults	O
+at	O
+risk	O
+for	O
+esophageal	O
+carcinoma	O
+(	O
+EC	O
+)	O
+in	O
+Transkei	O
+and	O
+Ciskei	O
+,	O
+Southern	O
+Africa	O
+.	O
+
+Aviators	O
+from	O
+the	O
+Light	O
+Attack	O
+Wing	O
+,	O
+Pacific	O
+were	O
+surveyed	O
+and	O
+the	O
+results	O
+were	O
+categorized	O
+by	O
+aircraft	O
+type	O
+.	O
+
+Evaluation	O
+of	O
+human	O
+and	O
+bovine	O
+modified	O
+-	O
+hemoglobin	B-GENE
+solution	O
+as	O
+oxygen	O
+-	O
+carrying	O
+fluid	O
+for	O
+blood	O
+volume	O
+replacement	O
+.	O
+
+Delayed	O
+gallbladder	O
+visualization	O
+and	O
+reduction	O
+in	O
+ejection	O
+fraction	O
+were	O
+sensitive	O
+but	O
+nonspecific	O
+indicators	O
+of	O
+biliary	O
+disease	O
+.	O
+
+26	O
+micrograms	O
+PAF	B-GENE
+or	O
+placebo	O
+was	O
+sprayed	O
+into	O
+each	O
+nasal	O
+cavity	O
+8	O
+h	O
+and	O
+1	O
+h	O
+before	O
+a	O
+nasal	O
+allergen	O
+challenge	O
+.	O
+
+Sci	O
+.	O
+
+Chem	O
+.	O
+
+Sequential	O
+MR	O
+examinations	O
+of	O
+the	O
+nasal	O
+cavity	O
+and	O
+paranasal	O
+sinuses	O
+were	O
+performed	O
+within	O
+a	O
+6	O
+-	O
+8	O
+h	O
+period	O
+in	O
+five	O
+normal	O
+volunteers	O
+.	O
+
+Comparison	O
+was	O
+made	O
+with	O
+other	O
+neuroradiological	O
+imaging	O
+modalities	O
+including	O
+CT	O
+,	O
+myelography	O
+,	O
+CT	O
+ventriculography	O
+,	O
+and	O
+CT	O
+myelocisternography	O
+.	O
+
+The	O
+feed	O
+given	O
+to	O
+young	O
+broiler	O
+chickens	O
+was	O
+contaminated	O
+artificially	O
+with	O
+Salmonella	O
+kedougou	O
+,	O
+a	O
+serotype	O
+associated	O
+with	O
+both	O
+subclinical	O
+infections	O
+in	O
+commercially	O
+reared	O
+chickens	O
+and	O
+food	O
+poisoning	O
+in	O
+humans	O
+.	O
+
+A	O
+poor	O
+correlation	O
+was	O
+found	O
+between	O
+a	O
+mildly	O
+-	O
+atypical	O
+(	O
+inflammatory	O
+)	O
+cytological	O
+result	O
+(	O
+class	O
+2	O
+)	O
+and	O
+a	O
+benign	O
+histological	O
+diagnosis	O
+:	O
+48	O
+%	O
+of	O
+class	O
+-	O
+2	O
+smears	O
+were	O
+diagnosed	O
+histologically	O
+as	O
+dysplasia	O
+or	O
+worse	O
+.	O
+
+Change	O
+in	O
+plasma	B-GENE
+cystyl	I-GENE
+aminopeptidase	I-GENE
+(	O
+oxytocinase	B-GENE
+)	O
+between	O
+30	O
+-	O
+34	O
+weeks	O
+'	O
+gestation	O
+as	O
+a	O
+predictor	O
+of	O
+pregnancy	O
+-	O
+induced	O
+hypertension	O
+.	O
+
+The	O
+test	O
+for	O
+alpha	B-GENE
+-	I-GENE
+naphthyl	I-GENE
+esterase	I-GENE
+and	O
+quantitation	O
+of	O
+macrophages	O
+(	O
+absolute	O
+number	O
+)	O
+per	O
+infiltration	O
+area	O
+unit	O
+adjacent	O
+to	O
+the	O
+abscess	O
+suggest	O
+a	O
+direct	O
+correlation	O
+between	O
+the	O
+absolute	O
+number	O
+of	O
+macrophages	O
+and	O
+the	O
+width	O
+of	O
+the	O
+capsule	O
+.	O
+
+Determined	O
+as	O
+migration	O
+differentials	O
+,	O
+chemotactic	O
+and	O
+chemokinetic	O
+responsiveness	O
+tended	O
+to	O
+be	O
+higher	O
+in	O
+the	O
+neutropenic	O
+group	O
+.	O
+
+The	O
+deduced	O
+96	O
+-	O
+residue	O
+amino	O
+acid	O
+coding	O
+sequence	O
+of	O
+the	O
+murine	O
+HMG	B-GENE
+-	I-GENE
+I	I-GENE
+(	I-GENE
+Y	I-GENE
+)	I-GENE
+cDNA	O
+is	O
+very	O
+similar	O
+to	O
+the	O
+reported	O
+amino	O
+acid	O
+sequence	O
+of	O
+human	O
+HMG	B-GENE
+-	I-GENE
+I	I-GENE
+,	O
+except	O
+that	O
+it	O
+lacks	O
+11	O
+internal	O
+amino	O
+acids	O
+reported	O
+in	O
+the	O
+human	O
+protein	O
+.	O
+
+Interpersonal	O
+style	O
+differences	O
+among	O
+drug	O
+abusers	O
+were	O
+explored	O
+using	O
+Ryan	O
+'	O
+s	O
+(	O
+1977	O
+)	O
+typological	O
+system	O
+of	O
+FIRO	O
+-	O
+B	O
+interpretation	O
+.	O
+
+Statement	O
+of	O
+the	O
+American	O
+Academy	O
+of	O
+Implant	O
+Dentistry	O
+.	O
+
+Sera	O
+from	O
+euthyroid	O
+post	O
+-	O
+menopausal	O
+or	O
+pregnant	O
+women	O
+yielded	O
+TSH	B-GENE
+levels	O
+within	O
+the	O
+normal	O
+range	O
+.	O
+
+No	O
+UOxase	B-GENE
+mRNA	I-GENE
+was	O
+detected	O
+in	O
+11	O
+nonhepatic	O
+tissues	O
+of	O
+rat	O
+,	O
+suggesting	O
+tissue	O
+specificity	O
+of	O
+expression	O
+of	O
+this	O
+UOxase	B-GENE
+gene	I-GENE
+.	O
+
+The	O
+platelet	O
+adhesion	O
+rate	O
+on	O
+these	O
+layers	O
+were	O
+tested	O
+concerning	O
+the	O
+valuation	O
+of	O
+the	O
+haemocompatibility	O
+of	O
+the	O
+basic	O
+-	O
+polymers	O
+polyurethane	O
+(	O
+PUR	O
+)	O
+,	O
+polyvinylchloride	O
+(	O
+PVC	O
+)	O
+,	O
+and	O
+polystyrene	O
+(	O
+PS	O
+)	O
+in	O
+two	O
+different	O
+worked	O
+test	O
+chambers	O
+.	O
+
+In	O
+a	O
+112	O
+-	O
+d	O
+feedlot	O
+trial	O
+,	O
+105	O
+heifers	O
+were	O
+assigned	O
+to	O
+light	O
+,	O
+medium	O
+and	O
+heavy	O
+weight	O
+blocks	O
+on	O
+five	O
+treatments	O
+:	O
+dietary	O
+MGA	O
+(	O
+.	O
+5	O
+mg	O
+.	O
+hd	O
+-	O
+1	O
+.	O
+d	O
+-	O
+1	O
+)	O
+,	O
+control	O
+(	O
+no	O
+MGA	O
+)	O
+or	O
+DEPO	O
+-	O
+MGA	O
+on	O
+d	O
+1	O
+at	O
+.	O
+5	O
+,	O
+1	O
+.	O
+0	O
+or	O
+1	O
+.	O
+5	O
+ml	O
+/	O
+hd	O
+(	O
+30	O
+,	O
+60	O
+or	O
+90	O
+mg	O
+MGA	O
+/	O
+hd	O
+,	O
+respectively	O
+)	O
+.	O
+
+Existence	O
+and	O
+uniqueness	O
+of	O
+solutions	O
+of	O
+the	O
+appropriate	O
+boundary	O
+value	O
+problems	O
+are	O
+established	O
+,	O
+in	O
+the	O
+case	O
+of	O
+small	O
+permeability	O
+coefficients	O
+and	O
+transport	O
+rates	O
+,	O
+or	O
+large	O
+diffusion	O
+coefficients	O
+and	O
+small	O
+resistance	O
+to	O
+flow	O
+constants	O
+.	O
+
+There	O
+were	O
+gene	O
+clusters	O
+encoding	O
+photosynthesis	O
+components	O
+such	O
+as	O
+the	O
+psbB	B-GENE
+-	O
+psbH	B-GENE
+-	O
+petB	B-GENE
+-	O
+petD	B-GENE
+and	O
+the	O
+psbE	O
+-	O
+psbF	O
+clusters	O
+.	O
+
+The	O
+partial	O
+sequence	O
+of	O
+the	O
+62	B-GENE
+-	I-GENE
+kDa	I-GENE
+nuclear	I-GENE
+pore	I-GENE
+glycoprotein	I-GENE
+shows	O
+little	O
+similarity	O
+to	O
+other	O
+characterized	O
+proteins	O
+and	O
+elucidates	O
+structural	O
+features	O
+of	O
+a	O
+member	O
+of	O
+the	O
+family	O
+of	O
+nuclear	B-GENE
+pore	I-GENE
+glycoproteins	I-GENE
+.	O
+
+Seventy	O
+-	O
+two	O
+hours	O
+after	O
+administration	O
+of	O
+vitamin	O
+K1	O
+,	O
+plasma	O
+concentrations	O
+of	O
+the	O
+vitamin	O
+were	O
+not	O
+different	O
+from	O
+normal	O
+.	O
+
+The	O
+glomerular	O
+filtration	O
+rate	O
+did	O
+not	O
+change	O
+but	O
+lithium	O
+clearance	O
+fell	O
+by	O
+30	O
+%	O
+.	O
+
+The	O
+pathogenesis	O
+of	O
+Dupuytren	O
+'	O
+s	O
+contracture	O
+
+An	O
+ELISA	O
+procedure	O
+was	O
+developed	O
+for	O
+monitoring	O
+the	O
+specific	O
+IgE	B-GENE
+response	O
+in	O
+dogs	O
+to	O
+Dirofilaria	O
+immitis	O
+infection	O
+.	O
+
+Fifty	O
+min	O
+after	O
+release	O
+from	O
+stress	O
+,	O
+increases	O
+in	O
+plasma	O
+corticosterone	O
+levels	O
+induced	O
+by	O
+stress	O
+recovered	O
+in	O
+the	O
+biting	O
+group	O
+but	O
+remained	O
+high	O
+in	O
+the	O
+non	O
+-	O
+biting	O
+group	O
+.	O
+
+The	O
+only	O
+isolate	O
+of	O
+Aeromonas	O
+hydrophila	O
+produced	O
+cytotoxic	O
+enterotoxin	O
+and	O
+was	O
+invasive	O
+.	O
+
+The	O
+incidence	O
+of	O
+early	O
+neonatal	O
+convulsions	O
+for	O
+inborn	O
+babies	O
+was	O
+3	O
+.	O
+0	O
+/	O
+1000	O
+live	O
+births	O
+.	O
+
+Of	O
+the	O
+43	O
+infants	O
+with	O
+a	O
+(	O
+probable	O
+)	O
+loss	O
+18	O
+were	O
+examined	O
+again	O
+at	O
+3	O
+months	O
+corrected	O
+age	O
+.	O
+
+Variety	O
+of	O
+cows	O
+and	O
+sires	O
+according	O
+to	O
+types	O
+of	O
+dermatoglyphics	O
+(	O
+patterns	O
+)	O
+of	O
+the	O
+nose	O
+-	O
+labial	O
+mirror	O
+of	O
+cattle	O
+
+Although	O
+not	O
+consistently	O
+identified	O
+in	O
+all	O
+samples	O
+,	O
+secondary	O
+Academic	O
+,	O
+Personal	O
+Responsibility	O
+,	O
+and	O
+Community	O
+/	O
+Vocational	O
+dimensions	O
+were	O
+also	O
+identified	O
+.	O
+
+Recovery	O
+was	O
+characterized	O
+by	O
+rapid	O
+improvement	O
+such	O
+that	O
+all	O
+measured	O
+parameters	O
+normalized	O
+by	O
+1	O
+week	O
+,	O
+except	O
+for	O
+cross	O
+-	O
+sectional	O
+cardiac	O
+area	O
+which	O
+remained	O
+dilated	O
+up	O
+to	O
+4	O
+weeks	O
+(	O
+14	O
++	O
+/	O
+-	O
+3	O
+cm2	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+versus	O
+control	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Not	O
+even	O
+extensive	O
+pancreatic	O
+resection	O
+could	O
+prevent	O
+pancreatic	O
+remnant	O
+infection	O
+.	O
+
+It	O
+has	O
+been	O
+calculated	O
+that	O
+600	O
+,	O
+000	O
+new	O
+cases	O
+of	O
+lung	O
+cancer	O
+occur	O
+worldwide	O
+every	O
+year	O
+,	O
+most	O
+of	O
+them	O
+due	O
+to	O
+smoking	O
+.	O
+
+Incorporation	O
+of	O
+0	O
+.	O
+1	O
+or	O
+0	O
+.	O
+2	O
+M	O
+sodium	O
+dihydrogen	O
+phosphate	O
+in	O
+the	O
+sugar	O
+solutions	O
+resulted	O
+in	O
+a	O
+decrease	O
+in	O
+the	O
+shelf	O
+-	O
+life	O
+of	O
+diltiazem	O
+.	O
+
+None	O
+had	O
+a	O
+past	O
+history	O
+of	O
+opportunistic	O
+infections	O
+;	O
+neither	O
+did	O
+any	O
+have	O
+lymphopenia	O
+.	O
+
+Increasing	O
+the	O
+phosphorus	O
+content	O
+of	O
+the	O
+diet	O
+improved	O
+the	O
+reabsorption	O
+of	O
+calcium	O
+and	O
+magnesium	O
+.	O
+
+Post	O
+-	O
+transcriptional	O
+regulation	O
+of	O
+ribosomal	B-GENE
+protein	I-GENE
+gene	I-GENE
+expression	O
+during	O
+development	O
+in	O
+Dictyostelium	O
+discoideum	O
+.	O
+
+The	O
+increase	O
+in	O
+amplitudes	O
+of	O
+the	O
+b	O
+-	O
+wave	O
+during	O
+the	O
+adaptation	O
+period	O
+was	O
+more	O
+prominent	O
+in	O
+lead	O
+-	O
+exposed	O
+subjects	O
+than	O
+in	O
+controls	O
+.	O
+
+Possible	O
+factors	O
+for	O
+the	O
+development	O
+of	O
+psychotic	O
+symptomatology	O
+during	O
+group	O
+activities	O
+and	O
+the	O
+role	O
+of	O
+group	O
+dynamics	O
+acting	O
+as	O
+stress	O
+factors	O
+precipitating	O
+functional	O
+psychoses	O
+,	O
+especially	O
+bipolar	O
+manifestations	O
+,	O
+are	O
+discussed	O
+.	O
+
+Baseline	O
+measurements	O
+of	O
+forced	O
+expiratory	O
+volume	O
+in	O
+1	O
+s	O
+(	O
+FEV1	O
+)	O
+,	O
+specific	O
+airway	O
+conductance	O
+(	O
+SGaw	O
+)	O
+and	O
+the	O
+provocative	O
+dose	O
+of	O
+carbachol	O
+causing	O
+a	O
+35	O
+%	O
+reduction	O
+in	O
+SGaw	O
+(	O
+PD35	O
+)	O
+,	O
+and	O
+a	O
+20	O
+%	O
+reduction	O
+in	O
+FEV1	O
+(	O
+PD20	O
+)	O
+were	O
+established	O
+on	O
+entry	O
+while	O
+each	O
+subject	O
+was	O
+still	O
+smoking	O
+.	O
+
+Many	O
+children	O
+with	O
+BGC	O
+are	O
+delayed	O
+in	O
+their	O
+development	O
+,	O
+but	O
+calcifications	O
+are	O
+not	O
+directly	O
+related	O
+to	O
+specific	O
+forms	O
+of	O
+neurologic	O
+dysfunction	O
+.	O
+
+R	O
+-	O
+wave	O
+voltage	O
+in	O
+the	O
+right	O
+precordial	O
+leads	O
+in	O
+anthracycline	O
+cardiomyopathy	O
+:	O
+a	O
+clinical	O
+study	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+the	O
+pooling	O
+requirements	O
+are	O
+task	O
+dependent	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+CSFHU	B-GENE
+can	O
+increase	O
+neutrophil	O
+counts	O
+by	O
+increasing	O
+the	O
+number	O
+and	O
+maturity	O
+of	O
+the	O
+marrow	O
+neutrophil	O
+precursors	O
+in	O
+some	O
+types	O
+of	O
+childhood	O
+chronic	O
+neutropenia	O
+.	O
+
+The	O
+purposes	O
+of	O
+this	O
+study	O
+were	O
+1	O
+)	O
+to	O
+examine	O
+the	O
+effect	O
+of	O
+high	O
+intensity	O
+,	O
+low	O
+frequency	O
+transcutaneous	O
+electrical	O
+nerve	O
+stimulation	O
+at	O
+auricular	O
+acupuncture	O
+points	O
+on	O
+experimental	O
+pain	O
+threshold	O
+measured	O
+at	O
+the	O
+wrist	O
+and	O
+2	O
+)	O
+to	O
+determine	O
+the	O
+changes	O
+in	O
+effect	O
+over	O
+time	O
+.	O
+
+In	O
+the	O
+infected	O
+neonates	O
+serum	O
+alpha	B-GENE
+-	I-GENE
+amylase	I-GENE
+value	O
+,	O
+as	O
+determined	O
+by	O
+the	O
+blue	O
+starch	O
+method	O
+,	O
+was	O
+only	O
+40	O
+%	O
+that	O
+of	O
+healthy	O
+controls	O
+;	O
+the	O
+mean	O
+value	O
+of	O
+175	O
+.	O
+1	O
++	O
+/	O
+-	O
+64	O
+.	O
+9	O
+IU	O
+/	O
+l	O
+for	O
+healthy	O
+neonates	O
+was	O
+significantly	O
+higher	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+0010	O
+)	O
+than	O
+the	O
+value	O
+of	O
+82	O
+.	O
+8	O
++	O
+/	O
+-	O
+44	O
+.	O
+4	O
+IU	O
+/	O
+l	O
+for	O
+the	O
+infected	O
+neonates	O
+.	O
+
+Records	O
+of	O
+31	O
+children	O
+with	O
+AIDS	O
+or	O
+AIDS	O
+-	O
+related	O
+complex	O
+admitted	O
+to	O
+the	O
+pediatric	O
+intensive	O
+care	O
+unit	O
+for	O
+acute	O
+respiratory	O
+failure	O
+throughout	O
+a	O
+46	O
+-	O
+month	O
+period	O
+were	O
+reviewed	O
+.	O
+
+SPECT	O
+is	O
+an	O
+important	O
+aid	O
+in	O
+the	O
+diagnosis	O
+of	O
+AIDS	O
+dementia	O
+complex	O
+and	O
+contributes	O
+to	O
+the	O
+understanding	O
+of	O
+the	O
+pathophysiological	O
+mechanisms	O
+of	O
+this	O
+disorder	O
+.	O
+
+We	O
+were	O
+interested	O
+in	O
+studying	O
+the	O
+relationship	O
+between	O
+the	O
+circadian	O
+rhythm	O
+in	O
+body	O
+temperature	O
+and	O
+24	O
+-	O
+h	O
+variations	O
+in	O
+plasma	O
+concentrations	O
+of	O
+iron	O
+,	O
+zinc	O
+,	O
+circulating	O
+leukocyte	O
+counts	O
+,	O
+and	O
+plasma	O
+interleukin	B-GENE
+1	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+activity	O
+.	O
+
+The	O
+murine	B-GENE
+MHC	I-GENE
+class	I-GENE
+I	I-GENE
+genes	I-GENE
+,	O
+H	B-GENE
+-	I-GENE
+2Dq	I-GENE
+and	O
+H	B-GENE
+-	I-GENE
+2Lq	I-GENE
+,	O
+are	O
+strikingly	O
+homologous	O
+to	O
+each	O
+other	O
+,	O
+H	B-GENE
+-	I-GENE
+2Ld	I-GENE
+,	O
+and	O
+two	O
+genes	O
+reported	O
+to	O
+encode	O
+tumor	O
+-	O
+specific	O
+antigens	O
+.	O
+
+The	O
+active	O
+derivatives	O
+of	O
+the	O
+present	O
+series	O
+were	O
+also	O
+tested	O
+for	O
+their	O
+analgesic	O
+activity	O
+against	O
+aconitine	O
+-	O
+induced	O
+writhing	O
+in	O
+albino	O
+mice	O
+and	O
+ulcerogenic	O
+activity	O
+in	O
+albino	O
+rats	O
+.	O
+
+In	O
+untreated	O
+mice	O
+,	O
+bactericidal	O
+activity	O
+of	O
+peritoneal	O
+macrophages	O
+decreased	O
+from	O
+one	O
+day	O
+to	O
+3	O
+days	O
+after	O
+ip	O
+injection	O
+of	O
+killed	O
+L	O
+.	O
+monocytogenes	O
+.	O
+
+Among	O
+a	O
+population	O
+of	O
+18	O
+,	O
+175	O
+children	O
+below	O
+7	O
+years	O
+of	O
+age	O
+in	O
+medium	O
+sized	O
+towns	O
+and	O
+rural	O
+areas	O
+in	O
+south	O
+-	O
+western	O
+Germany	O
+552	O
+(	O
+3	O
+.	O
+03	O
+%	O
+)	O
+cases	O
+of	O
+croup	O
+were	O
+registered	O
+during	O
+a	O
+12	O
+months	O
+period	O
+in	O
+1984	O
+-	O
+85	O
+by	O
+their	O
+physicians	O
+.	O
+
+We	O
+concluded	O
+that	O
+Ga	O
+-	O
+fbg	O
+scintigraphy	O
+is	O
+a	O
+very	O
+simple	O
+method	O
+and	O
+sufficiently	O
+useful	O
+for	O
+detecting	O
+active	O
+left	O
+ventricular	O
+thrombi	O
+and	O
+for	O
+monitoring	O
+the	O
+effect	O
+of	O
+anticoagulant	O
+therapy	O
+.	O
+
+In	O
+vitro	O
+assessment	O
+of	O
+the	O
+biocompatibility	O
+of	O
+dental	O
+materials	O
+-	O
+-	O
+the	O
+millipore	O
+filter	O
+method	O
+.	O
+
+Hypomagnesemia	O
+was	O
+due	O
+to	O
+magnesium	O
+wasting	O
+by	O
+the	O
+kidney	O
+.	O
+
+Dentalplaque	O
+was	O
+controlled	O
+by	O
+the	O
+oral	O
+higienic	O
+index	O
+of	O
+the	O
+whole	O
+dentition	O
+daily	O
+,	O
+after	O
+staining	O
+with	O
+1	O
+per	O
+cent	O
+alkaline	O
+fuxin	O
+.	O
+
+GRFI	B-GENE
+bound	O
+to	O
+sequences	O
+at	O
+the	O
+negative	O
+regulatory	O
+elements	O
+(	O
+silencers	O
+)	O
+of	O
+the	O
+silent	B-GENE
+mating	I-GENE
+type	I-GENE
+loci	I-GENE
+HML	B-GENE
+E	I-GENE
+and	O
+HMR	B-GENE
+E	I-GENE
+and	O
+to	O
+the	O
+upstream	O
+activating	O
+sequence	O
+(	O
+UAS	O
+)	O
+required	O
+for	O
+transcription	O
+of	O
+the	O
+MAT	B-GENE
+alpha	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+effects	O
+of	O
+these	O
+mutations	O
+on	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+activity	O
+were	O
+assayed	O
+by	O
+measuring	O
+the	O
+ability	O
+of	O
+mutant	O
+genes	O
+to	O
+confer	O
+alpha	B-GENE
+-	I-GENE
+amanitin	I-GENE
+resistance	O
+after	O
+transfection	O
+of	O
+susceptible	O
+rodent	O
+cells	O
+.	O
+
+We	O
+report	O
+the	O
+use	O
+of	O
+a	O
+new	O
+technetium	O
+-	O
+99m	O
+-	O
+albumin	B-GENE
+colloid	O
+white	O
+blood	O
+cell	O
+(	O
+TAC	O
+-	O
+WBC	O
+)	O
+scan	O
+in	O
+the	O
+evaluation	O
+of	O
+appendicitis	O
+.	O
+
+In	O
+one	O
+of	O
+these	O
+tumors	O
+the	O
+observed	O
+rearrangement	O
+was	O
+not	O
+due	O
+to	O
+the	O
+insertion	O
+of	O
+an	O
+intact	O
+MoMuLV	O
+provirus	O
+.	O
+
+The	O
+indications	O
+for	O
+its	O
+use	O
+include	O
+every	O
+primary	O
+and	O
+secondary	O
+rhinoplasty	O
+candidate	O
+unless	O
+tip	O
+grafts	O
+are	O
+going	O
+to	O
+be	O
+under	O
+tension	O
+or	O
+if	O
+the	O
+deformity	O
+is	O
+minor	O
+.	O
+
+Mutations	O
+at	O
+the	O
+suf12	B-GENE
+locus	I-GENE
+were	O
+isolated	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+as	O
+extragenic	O
+suppressors	O
+of	O
++	O
+1	O
+frameshift	O
+mutations	O
+in	O
+glycine	O
+(	O
+GGX	O
+)	O
+and	O
+proline	O
+(	O
+CCX	O
+)	O
+codons	O
+,	O
+as	O
+well	O
+as	O
+UGA	O
+and	O
+UAG	O
+nonsense	O
+mutations	O
+.	O
+
+The	O
+behavior	O
+of	O
+suf12	B-GENE
+-	I-GENE
+null	I-GENE
+/	I-GENE
+SUF12	I-GENE
++	I-GENE
+heterozygotes	I-GENE
+indicates	O
+that	O
+suf12	B-GENE
+is	O
+co	O
+-	O
+dominantly	O
+expressed	O
+and	O
+suggests	O
+that	O
+suf12	B-GENE
+allele	O
+-	O
+specific	O
+suppression	O
+may	O
+result	O
+from	O
+functionally	O
+distinct	O
+mutant	O
+proteins	O
+rather	O
+than	O
+variation	O
+in	O
+residual	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+SUF12	I-GENE
++	I-GENE
+activity	O
+.	O
+
+Antituberculosis	O
+agents	O
+.	O
+
+The	O
+putative	O
+immunity	O
+protein	O
+was	O
+detected	O
+among	O
+the	O
+[	O
+35S	O
+]	O
+methionine	O
+-	O
+labelled	O
+proteins	O
+produced	O
+by	O
+minicells	O
+carrying	O
+cni	B-GENE
+cloned	O
+under	O
+lac	B-GENE
+promoter	I-GENE
+control	O
+,	O
+and	O
+when	O
+the	O
+gene	O
+was	O
+subcloned	O
+into	O
+expression	O
+vectors	O
+under	O
+the	O
+control	O
+of	O
+a	O
+bacteriophage	O
+T7	O
+promoter	O
+.	O
+
+Antibodies	O
+made	O
+against	O
+fusion	O
+protein	O
+produced	O
+by	O
+the	O
+DP1A	B-GENE
+clone	O
+reacted	O
+specifically	O
+with	O
+DP	B-GENE
+-	I-GENE
+I	I-GENE
+and	I-GENE
+-	I-GENE
+II	I-GENE
+on	O
+immunoblots	O
+.	O
+
+Finally	O
+,	O
+over	O
+a	O
+similar	O
+range	O
+of	O
+QO2	O
+,	O
+oxygen	O
+extraction	O
+was	O
+greater	O
+in	O
+patients	O
+with	O
+ARDS	O
+compared	O
+to	O
+patients	O
+with	O
+non	O
+-	O
+ARDS	O
+respiratory	O
+failure	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+67	O
+and	O
+slope	O
+=	O
+-	O
+0	O
+.	O
+62	O
+vs	O
+r	O
+=	O
+-	O
+0	O
+.	O
+45	O
+and	O
+slope	O
+=	O
+-	O
+0	O
+.	O
+35	O
+;	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Stable	O
+patients	O
+have	O
+mucous	O
+hypersecretion	O
+and	O
+little	O
+evidence	O
+of	O
+acute	O
+inflammation	O
+.	O
+
+Hyperprolactinaemia	O
+,	O
+moderate	O
+hypogonadism	O
+,	O
+infraclinical	O
+neuropathies	O
+,	O
+arterial	O
+stenoses	O
+and	O
+moderate	O
+venous	O
+leakages	O
+seem	O
+to	O
+play	O
+a	O
+partial	O
+role	O
+of	O
+organic	O
+starter	O
+or	O
+cofactor	O
+,	O
+the	O
+sexual	O
+consequences	O
+of	O
+which	O
+are	O
+amplified	O
+by	O
+psychological	O
+factors	O
+,	O
+partly	O
+secondary	O
+to	O
+the	O
+initial	O
+sexual	O
+failures	O
+.	O
+
+Yang	O
+and	O
+H	O
+.	O
+
+Secretory	O
+function	O
+of	O
+the	O
+prostate	O
+gland	O
+.	O
+
+Chronic	O
+endotoxemia	O
+appears	O
+to	O
+be	O
+associated	O
+with	O
+an	O
+elevated	O
+pulmonary	O
+microvascular	O
+permeability	O
+and	O
+a	O
+tendency	O
+toward	O
+a	O
+hyperdynamic	O
+circulation	O
+but	O
+with	O
+an	O
+appreciable	O
+degree	O
+of	O
+refractoriness	O
+associated	O
+with	O
+regional	O
+hemodynamics	O
+and	O
+eicosanoid	O
+biosynthesis	O
+.	O
+
+In	O
+contrast	O
+,	O
+we	O
+observed	O
+high	O
+concentrations	O
+in	O
+29	O
+of	O
+75	O
+patients	O
+with	O
+tumors	O
+of	O
+the	O
+central	O
+nervous	O
+system	O
+,	O
+especially	O
+in	O
+meningioma	O
+(	O
+6	O
+/	O
+9	O
+)	O
+,	O
+glioblastoma	O
+(	O
+9	O
+/	O
+23	O
+)	O
+,	O
+and	O
+neurinoma	O
+(	O
+5	O
+/	O
+5	O
+)	O
+.	O
+
+Diet	O
+and	O
+atopic	O
+eczema	O
+.	O
+
+Time	O
+delay	O
+effects	O
+on	O
+the	O
+tensile	O
+bond	O
+strength	O
+developed	O
+by	O
+the	O
+Silicoater	O
+.	O
+
+The	O
+future	O
+of	O
+research	O
+with	O
+interferon	B-GENE
+may	O
+be	O
+divided	O
+into	O
+three	O
+areas	O
+:	O
+Efforts	O
+must	O
+be	O
+made	O
+to	O
+determine	O
+how	O
+best	O
+to	O
+translate	O
+the	O
+in	O
+vitro	O
+synergy	O
+into	O
+clinically	O
+meaningful	O
+terms	O
+;	O
+in	O
+order	O
+to	O
+exploit	O
+the	O
+fullest	O
+potential	O
+of	O
+IFN	B-GENE
+,	O
+research	O
+is	O
+moving	O
+toward	O
+using	O
+this	O
+agent	O
+earlier	O
+in	O
+disease	O
+either	O
+as	O
+an	O
+adjuvant	O
+after	O
+tumor	O
+debulking	O
+or	O
+after	O
+initial	O
+diagnosis	O
+;	O
+the	O
+medical	O
+community	O
+must	O
+rethink	O
+the	O
+natural	O
+history	O
+of	O
+some	O
+diseases	O
+,	O
+because	O
+the	O
+fullest	O
+potential	O
+of	O
+the	O
+biologic	O
+agents	O
+will	O
+most	O
+likely	O
+manifest	O
+itself	O
+when	O
+these	O
+agents	O
+are	O
+used	O
+together	O
+.	O
+
+Six	O
+healthy	O
+male	O
+subjects	O
+received	O
+single	O
+oral	O
+doses	O
+of	O
+regular	O
+release	O
+(	O
+RR	O
+)	O
+quinidine	O
+sulfate	O
+,	O
+sustained	O
+release	O
+(	O
+SR	O
+)	O
+quinidine	O
+bisulfate	O
+and	O
+the	O
+same	O
+dose	O
+of	O
+the	O
+SR	O
+product	O
+with	O
+food	O
+(	O
+SR	O
+-	O
+F	O
+)	O
+.	O
+
+This	O
+report	O
+expands	O
+on	O
+previous	O
+work	O
+with	O
+interferon	B-GENE
+alfa	I-GENE
+-	I-GENE
+2b	I-GENE
+(	I-GENE
+Intron	I-GENE
+A	I-GENE
+;	I-GENE
+Schering	I-GENE
+-	I-GENE
+Plough	I-GENE
+)	I-GENE
+in	O
+the	O
+treatment	O
+of	O
+hairy	O
+cell	O
+leukemia	O
+(	O
+HCL	O
+)	O
+.	O
+
+Oxygen	O
+delivery	O
+and	O
+base	O
+excess	O
+decreased	O
+significantly	O
+and	O
+four	O
+pigs	O
+died	O
+.	O
+
+Clinical	O
+chemistry	O
+.	O
+
+Revascularization	O
+after	O
+anterior	O
+maxillary	O
+and	O
+mandibular	O
+osteotomy	O
+
+Static	O
+orthoses	O
+for	O
+the	O
+management	O
+of	O
+microstomia	O
+.	O
+
+The	O
+intrapancreatic	O
+spread	O
+of	O
+the	O
+carcinoma	O
+correlated	O
+with	O
+portal	O
+invasion	O
+of	O
+carcinoma	O
+,	O
+hardness	O
+of	O
+the	O
+body	O
+and	O
+tail	O
+,	O
+obstruction	O
+of	O
+main	O
+pancreatic	O
+duct	O
+and	O
+irregular	O
+pancreaticogram	O
+.	O
+
+Lysosomal	O
+enzymes	O
+that	O
+degrade	O
+cartilage	O
+are	O
+released	O
+.	O
+
+Contrary	O
+to	O
+the	O
+observation	O
+made	O
+with	O
+other	O
+S	O
+.	O
+pombe	O
+genes	O
+transcribed	O
+in	O
+the	O
+budding	O
+yeast	O
+,	O
+the	O
+heterologous	O
+actin	B-GENE
+gene	I-GENE
+transcript	I-GENE
+is	O
+initiated	O
+39	O
+nucleotides	O
+upstream	O
+of	O
+the	O
+initiation	O
+start	O
+site	O
+used	O
+in	O
+the	O
+homologous	O
+yeast	O
+.	O
+
+A	O
+multicentre	O
+study	O
+involving	O
+9	O
+Italian	O
+institutions	O
+was	O
+carried	O
+out	O
+to	O
+compare	O
+the	O
+efficacy	O
+and	O
+safety	O
+of	O
+ranitidine	O
+150	O
+mg	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+and	O
+ranitidine	O
+300	O
+mg	O
+nocte	O
+in	O
+the	O
+treatment	O
+of	O
+reflux	O
+oesophagitis	O
+.	O
+
+Monotherapy	O
+with	O
+ceftazidime	O
+was	O
+clinically	O
+and	O
+bacteriologically	O
+as	O
+effective	O
+as	O
+a	O
+combination	O
+therapy	O
+with	O
+cefazolin	O
+and	O
+tobramycin	O
+.	O
+
+The	O
+N3	O
+wave	O
+of	O
+the	O
+SSEP	O
+'	O
+s	O
+,	O
+which	O
+has	O
+been	O
+found	O
+to	O
+correlate	O
+best	O
+with	O
+neurological	O
+recovery	O
+,	O
+returned	O
+to	O
+65	O
+%	O
++	O
+/	O
+-	O
+48	O
+%	O
+of	O
+the	O
+preischemia	O
+amplitude	O
+in	O
+the	O
+insulin	B-GENE
+-	O
+treated	O
+animals	O
+,	O
+compared	O
+to	O
+40	O
+%	O
++	O
+/	O
+-	O
+34	O
+%	O
+in	O
+the	O
+fasted	O
+group	O
+and	O
+26	O
+%	O
++	O
+/	O
+-	O
+24	O
+%	O
+in	O
+the	O
+control	O
+animals	O
+.	O
+
+Proctoscopy	O
+and	O
+roentgenographic	O
+studies	O
+may	O
+be	O
+an	O
+important	O
+part	O
+of	O
+evaluation	O
+,	O
+especially	O
+in	O
+patients	O
+who	O
+present	O
+with	O
+perianal	O
+suppuration	O
+,	O
+masses	O
+,	O
+or	O
+anal	O
+fissures	O
+.	O
+
+In	O
+the	O
+control	O
+group	O
+the	O
+histological	O
+picture	O
+resembled	O
+osteoarthritis	O
+.	O
+
+In	O
+contrast	O
+to	O
+this	O
+mRNA	O
+,	O
+90	O
+%	O
+of	O
+alpha	B-GENE
+and	I-GENE
+beta	I-GENE
+actin	I-GENE
+mRNAs	I-GENE
+were	O
+translated	O
+in	O
+both	O
+myoblasts	O
+and	O
+myotubes	O
+.	O
+
+If	O
+this	O
+is	O
+unavailable	O
+,	O
+then	O
+Supramid	O
+has	O
+a	O
+proven	O
+record	O
+for	O
+good	O
+tissue	O
+compatibility	O
+and	O
+resistance	O
+to	O
+infection	O
+.	O
+
+The	O
+size	O
+of	O
+the	O
+group	O
+allocated	O
+to	O
+the	O
+good	O
+compliance	O
+category	O
+by	O
+the	O
+use	O
+of	O
+the	O
+digoxin	O
+marker	O
+was	O
+equivalent	O
+in	O
+size	O
+to	O
+a	O
+group	O
+of	O
+patients	O
+who	O
+had	O
+returned	O
+less	O
+than	O
+15	O
+%	O
+of	O
+their	O
+prescribed	O
+dose	O
+or	O
+reported	O
+a	O
+deviation	O
+of	O
+less	O
+than	O
+6	O
+%	O
+from	O
+their	O
+prescription	O
+.	O
+
+Bullous	O
+keratopathy	O
+was	O
+usually	O
+aphakic	O
+in	O
+origin	O
+in	O
+1982	O
+,	O
+but	O
+after	O
+1983	O
+pseudophakic	O
+bullous	O
+keratopathy	O
+(	O
+PBK	O
+)	O
+was	O
+the	O
+most	O
+common	O
+cause	O
+of	O
+bullous	O
+keratopathy	O
+.	O
+
+The	O
+ultrastructural	O
+findings	O
+,	O
+as	O
+well	O
+as	O
+the	O
+urinary	O
+C	B-GENE
+-	I-GENE
+peptide	I-GENE
+excretion	O
+,	O
+confirmed	O
+that	O
+the	O
+glycemic	O
+effects	O
+should	O
+not	O
+be	O
+thought	O
+to	O
+be	O
+due	O
+to	O
+a	O
+direct	O
+action	O
+of	O
+the	O
+drugs	O
+used	O
+on	O
+the	O
+endocrine	O
+pancreas	O
+.	O
+
+In	O
+vitro	O
+antimalarial	O
+activity	O
+of	O
+neem	O
+(	O
+Azadirachta	O
+indica	O
+A	O
+.	O
+
+"	O
+In	O
+vitro	O
+"	O
+study	O
+of	O
+dentin	O
+adhesion	O
+to	O
+adhesives	O
+made	O
+from	O
+urethane	O
+molecules	O
+with	O
+free	O
+groups	O
+of	O
+isocyanate	O
+
+There	O
+is	O
+a	O
+cysteine	O
+clustering	O
+region	O
+in	O
+an	O
+N	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+raf	I-GENE
+(	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+product	I-GENE
+deduced	O
+from	O
+the	O
+nucleotide	O
+sequence	O
+,	O
+and	O
+this	O
+cysteine	O
+clustering	O
+region	O
+was	O
+found	O
+to	O
+be	O
+highly	O
+homologous	O
+to	O
+that	O
+present	O
+in	O
+an	O
+N	O
+-	O
+terminal	O
+region	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+,	O
+although	O
+,	O
+in	O
+the	O
+latter	O
+cysteine	O
+clusters	O
+are	O
+present	O
+in	O
+duplicate	O
+.	O
+
+Hand	O
+-	O
+held	O
+,	O
+continuous	O
+-	O
+wave	O
+Doppler	O
+probes	O
+,	O
+coupled	O
+with	O
+sound	O
+spectral	O
+analysis	O
+,	O
+can	O
+successfully	O
+predict	O
+carotid	O
+artery	O
+stenosis	O
+.	O
+
+The	O
+German	O
+Society	O
+of	O
+Pediatric	O
+Oncology	O
+in	O
+1981	O
+initiated	O
+the	O
+Cooperative	O
+Ewing	O
+'	O
+s	O
+Sarcoma	O
+Study	O
+(	O
+CESS	O
+81	O
+)	O
+using	O
+a	O
+four	O
+-	O
+drug	O
+combination	O
+of	O
+chemotherapy	O
+prior	O
+to	O
+definitive	O
+local	O
+control	O
+with	O
+surgery	O
+and	O
+/	O
+or	O
+radiation	O
+.	O
+
+The	O
+program	O
+has	O
+been	O
+written	O
+in	O
+a	O
+generic	O
+BASIC	O
+in	O
+order	O
+to	O
+make	O
+the	O
+procedure	O
+user	O
+-	O
+friendly	O
+.	O
+
+Since	O
+high	O
+levels	O
+of	O
+immunoglobulin	B-GENE
+G	I-GENE
+were	O
+demonstrated	O
+against	O
+the	O
+surface	O
+of	O
+the	O
+NVS	O
+after	O
+immunization	O
+,	O
+passive	O
+transfer	O
+experiments	O
+were	O
+initiated	O
+.	O
+
+A	O
+study	O
+was	O
+conducted	O
+of	O
+a	O
+human	O
+male	O
+who	O
+had	O
+inhaled	O
+a	O
+mixture	O
+of	O
+241Am	O
+and	O
+Pu	O
+.	O
+
+An	O
+analytic	O
+method	O
+for	O
+comparative	O
+parameter	O
+weighting	O
+in	O
+magnetic	O
+resonance	O
+(	O
+MR	O
+)	O
+imaging	O
+has	O
+been	O
+developed	O
+using	O
+the	O
+concept	O
+of	O
+"	O
+fractional	O
+sensitivity	O
+.	O
+"	O
+This	O
+new	O
+approach	O
+results	O
+in	O
+easily	O
+calculated	O
+indexes	O
+for	O
+T1	O
+,	O
+T2	O
+,	O
+and	O
+hydrogen	O
+weighting	O
+.	O
+
+Fifty	O
+-	O
+four	O
+patients	O
+were	O
+divided	O
+into	O
+groups	O
+according	O
+to	O
+their	O
+clinical	O
+presentation	O
+;	O
+seven	O
+asymptomatic	O
+volunteers	O
+,	O
+20	O
+patients	O
+with	O
+duodenal	O
+-	O
+gastric	O
+reflux	O
+gastropathy	O
+(	O
+DRG	O
+)	O
+,	O
+16	O
+patients	O
+with	O
+recurrent	O
+ulcers	O
+of	O
+the	O
+duodenal	O
+bulb	O
+(	O
+RUD	O
+)	O
+,	O
+and	O
+11	O
+patients	O
+with	O
+Moynihan	O
+'	O
+s	O
+disease	O
+.	O
+
+No	O
+previous	O
+studies	O
+have	O
+determined	O
+the	O
+pharmaco	O
+-	O
+dynamics	O
+of	O
+intravenous	O
+procainamide	O
+when	O
+administered	O
+in	O
+a	O
+dose	O
+of	O
+15	O
+mg	O
+/	O
+kg	O
+and	O
+at	O
+a	O
+rate	O
+of	O
+50	O
+mg	O
+/	O
+min	O
+,	O
+as	O
+is	O
+common	O
+practice	O
+during	O
+electropharmacologic	O
+testing	O
+.	O
+
+High	O
+concentrations	O
+of	O
+tumor	O
+-	O
+associated	O
+trypsin	B-GENE
+inhibitor	O
+in	O
+hemodialyzed	O
+patients	O
+.	O
+
+In	O
+the	O
+chicken	O
+liver	O
+,	O
+levels	O
+of	O
+chicken	B-GENE
+MT	I-GENE
+mRNA	I-GENE
+were	O
+rapidly	O
+induced	O
+by	O
+metals	O
+(	O
+Cd2	O
++	O
+,	O
+Zn2	O
++	O
+,	O
+Cu2	O
++	O
+)	O
+,	O
+glucocorticoids	O
+and	O
+lipopolysaccharide	O
+.	O
+
+With	O
+histology	O
+and	O
+Evans	O
+blue	O
+injections	O
+,	O
+blood	O
+-	O
+brain	O
+barrier	O
+alterations	O
+were	O
+seen	O
+as	O
+early	O
+as	O
+4	O
+days	O
+after	O
+a	O
+dose	O
+of	O
+50	O
+Gy	O
+.	O
+
+Dosimetric	O
+estimates	O
+for	O
+these	O
+organs	O
+were	O
+2	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+and	O
+2	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+rad	O
+(	O
+.	O
+02	O
++	O
+/	O
+-	O
+.	O
+01	O
+Gy	O
+)	O
+,	O
+respectively	O
+,	O
+with	O
+a	O
+whole	O
+-	O
+body	O
+estimate	O
+of	O
+0	O
+.	O
+28	O
+rad	O
+(	O
+.	O
+003	O
+Gy	O
+)	O
+.	O
+
+A	O
+significant	O
+association	O
+between	O
+a	O
+family	O
+history	O
+and	O
+a	O
+higher	O
+urinary	O
+pH	O
+was	O
+observed	O
+among	O
+the	O
+female	O
+calcium	O
+stone	O
+patients	O
+.	O
+
+New	O
+technologies	O
+in	O
+diagnosis	O
+and	O
+classification	O
+of	O
+malignancy	O
+.	O
+
+Thus	O
+the	O
+present	O
+data	O
+also	O
+suggest	O
+that	O
+BP	O
+and	O
+HR	O
+measurements	O
+are	O
+influenced	O
+not	O
+only	O
+by	O
+state	O
+-	O
+dependent	O
+factors	O
+but	O
+also	O
+by	O
+at	O
+least	O
+three	O
+different	O
+factors	O
+that	O
+are	O
+each	O
+independent	O
+of	O
+the	O
+state	O
+:	O
+one	O
+leads	O
+to	O
+BP	O
+and	O
+HR	O
+values	O
+that	O
+are	O
+influenced	O
+by	O
+the	O
+cycle	O
+the	O
+animal	O
+is	O
+in	O
+and	O
+the	O
+other	O
+two	O
+influence	O
+,	O
+respectively	O
+,	O
+the	O
+ranking	O
+of	O
+the	O
+individual	O
+'	O
+s	O
+BP	O
+and	O
+HR	O
+levels	O
+within	O
+the	O
+population	O
+.	O
+
+The	O
+correlation	O
+between	O
+PaCO2	O
+and	O
+PtcO2	O
+in	O
+RDS	O
+was	O
+insufficient	O
+to	O
+make	O
+clinical	O
+judgement	O
+.	O
+
+Since	O
+1967	O
+at	O
+the	O
+times	O
+of	O
+their	O
+biennial	O
+ABCC	O
+/	O
+RERF	O
+radiological	O
+examinations	O
+,	O
+all	O
+Adult	O
+Health	O
+Study	O
+(	O
+AHS	O
+)	O
+subjects	O
+have	O
+been	O
+interviewed	O
+to	O
+determine	O
+the	O
+exposures	O
+to	O
+medical	O
+x	O
+-	O
+rays	O
+they	O
+experienced	O
+in	O
+institutions	O
+other	O
+than	O
+RERF	O
+in	O
+order	O
+to	O
+estimate	O
+the	O
+numbers	O
+of	O
+examinations	O
+and	O
+corresponding	O
+doses	O
+which	O
+they	O
+received	O
+.	O
+
+One	O
+millimolar	O
+ouabain	O
+completely	O
+inhibited	O
+net	O
+HCO3	O
+-	O
+secretion	O
+.	O
+
+There	O
+are	O
+regions	O
+with	O
+long	O
+runs	O
+of	O
+up	O
+to	O
+45	O
+%	O
+C	O
+or	O
+35	O
+%	O
+G	O
+residues	O
+.	O
+
+The	O
+same	O
+rhythmic	O
+structure	O
+enables	O
+a	O
+prediction	O
+to	O
+be	O
+made	O
+concerning	O
+when	O
+vowels	O
+of	O
+stressed	O
+syllables	O
+will	O
+be	O
+auditorily	O
+perceived	O
+.	O
+
+Vocal	O
+cord	O
+abduction	O
+rehabilitation	O
+by	O
+nervous	O
+selective	O
+anastomosis	O
+.	O
+
+UK	O
+'	O
+s	O
+biotechnology	O
+lacking	O
+specialists	O
+.	O
+
+Distant	O
+spread	O
+was	O
+found	O
+in	O
+46	O
+patients	O
+(	O
+34	O
+%	O
+)	O
+,	O
+42	O
+of	O
+whom	O
+had	O
+serum	O
+Tg	B-GENE
+greater	O
+than	O
+10	O
+micrograms	O
+/	O
+l	O
+.	O
+
+The	O
+glomerular	O
+filtration	O
+rate	O
+and	O
+effective	O
+renal	O
+plasma	O
+flow	O
+were	O
+determined	O
+by	O
+a	O
+standard	O
+clearance	O
+method	O
+,	O
+employing	O
+continuous	O
+infusion	O
+of	O
+inulin	O
+and	O
+para	O
+-	O
+aminohippuric	O
+acid	O
+.	O
+
+After	O
+the	O
+meal	O
+containing	O
+potato	O
+,	O
+plasma	O
+glucose	O
+levels	O
+rose	O
+sharply	O
+,	O
+peaked	O
+at	O
+30	O
+-	O
+45	O
+min	O
+and	O
+fell	O
+below	O
+initial	O
+levels	O
+2	O
+to	O
+3	O
+h	O
+later	O
+.	O
+
+The	O
+relations	O
+among	O
+various	O
+negative	O
+emotional	O
+and	O
+behavioral	O
+characteristics	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+aggression	O
+,	O
+anxiety	O
+,	O
+undercompliance	O
+,	O
+depressive	O
+mood	O
+)	O
+and	O
+adjustment	O
+were	O
+examined	O
+through	O
+use	O
+of	O
+data	O
+from	O
+the	O
+31	O
+-	O
+year	O
+-	O
+old	O
+New	O
+York	O
+Longitudinal	O
+Study	O
+.	O
+
+To	O
+evaluate	O
+the	O
+effect	O
+of	O
+altitude	O
+on	O
+adolescent	O
+growth	O
+and	O
+development	O
+,	O
+three	O
+groups	O
+of	O
+healthy	O
+,	O
+well	O
+-	O
+nourished	O
+youth	O
+of	O
+similar	O
+socioeconomic	O
+status	O
+and	O
+ethnic	O
+grouping	O
+who	O
+resided	O
+at	O
+sea	O
+level	O
+(	O
+n	O
+=	O
+1262	O
+subjects	O
+)	O
+,	O
+mid	O
+-	O
+altitude	O
+(	O
+n	O
+=	O
+1743	O
+subjects	O
+)	O
+,	O
+and	O
+high	O
+altitude	O
+(	O
+n	O
+=	O
+1137	O
+subjects	O
+)	O
+were	O
+studied	O
+.	O
+
+Because	O
+the	O
+CAP	O
+measures	O
+variables	O
+predictive	O
+of	O
+abusive	O
+behavior	O
+,	O
+a	O
+substantial	O
+relationship	O
+was	O
+expected	O
+between	O
+the	O
+CAP	O
+and	O
+the	O
+MHI	O
+Loss	O
+of	O
+Behavioral	O
+/	O
+Emotional	O
+Control	O
+scale	O
+.	O
+
+We	O
+have	O
+improved	O
+our	O
+system	O
+for	O
+nuclear	O
+contour	O
+digitization	O
+and	O
+determined	O
+its	O
+theoretical	O
+limitations	O
+by	O
+digitizing	O
+standardized	O
+objects	O
+.	O
+
+Such	O
+a	O
+change	O
+may	O
+involve	O
+increased	O
+mammary	O
+utilization	O
+of	O
+pre	O
+-	O
+formed	O
+long	O
+-	O
+chain	O
+fatty	O
+acid	O
+and	O
+increased	O
+metabolism	O
+of	O
+glucose	O
+via	O
+glycolysis	O
+.	O
+
+The	O
+skin	O
+site	O
+,	O
+6	O
+-	O
+cm	O
+-	O
+distal	O
+and	O
+-	O
+proximal	O
+subcutaneous	O
+segments	O
+of	O
+the	O
+catheter	O
+,	O
+exudates	O
+,	O
+and	O
+blood	O
+were	O
+cultured	O
+.	O
+
+Because	O
+of	O
+its	O
+great	O
+reliability	O
+,	O
+conventional	O
+arteriography	O
+occupies	O
+a	O
+place	O
+of	O
+choice	O
+among	O
+the	O
+medical	O
+imaging	O
+techniques	O
+.	O
+
+Rapid	O
+detection	O
+of	O
+radioisotopically	O
+contaminated	O
+test	O
+serum	O
+before	O
+radioassay	O
+of	O
+vitamin	O
+B12	O
+.	O
+
+The	O
+former	O
+group	O
+did	O
+excrete	O
+less	O
+dry	O
+fecal	O
+material	O
+compared	O
+to	O
+both	O
+other	O
+groups	O
+.	O
+
+Electronic	O
+data	O
+processing	O
+(	O
+EDP	O
+)	O
+latex	O
+immunoassay	O
+using	O
+anti	B-GENE
+-	I-GENE
+human	I-GENE
+seminal	I-GENE
+acid	I-GENE
+phosphatase	I-GENE
+(	O
+anti	B-GENE
+-	I-GENE
+HSAP	I-GENE
+)	O
+immune	O
+serum	O
+was	O
+applied	O
+for	O
+the	O
+species	O
+and	O
+organ	O
+identification	O
+of	O
+human	O
+seminal	O
+stains	O
+.	O
+
+The	O
+maximum	O
+deflections	O
+of	O
+phase	O
+IV	O
+for	O
+Ar	O
+and	O
+N2	O
+from	O
+extrapolated	O
+phase	O
+III	O
+slopes	O
+were	O
+smaller	O
+in	O
+the	O
+prone	O
+position	O
+,	O
+suggesting	O
+more	O
+uniform	O
+tracer	O
+gas	O
+concentrations	O
+across	O
+the	O
+lungs	O
+.	O
+
+Recent	O
+developments	O
+in	O
+drugs	O
+antagonistic	O
+to	O
+factors	O
+causing	O
+peptic	O
+ulcer	O
+-	O
+-	O
+clinical	O
+efficacy	O
+and	O
+problems	O
+;	O
+gastrin	B-GENE
+receptor	I-GENE
+blockaders	O
+
+Static	O
+magnetic	O
+fields	O
+affect	O
+the	O
+diffusion	O
+of	O
+biological	O
+particles	O
+in	O
+solutions	O
+through	O
+the	O
+Lorentz	O
+force	O
+and	O
+Maxwell	O
+stress	O
+.	O
+
+Psychological	O
+disturbance	O
+was	O
+greater	O
+in	O
+the	O
+high	O
+life	O
+stress	O
+group	O
+as	O
+indicated	O
+by	O
+significant	O
+elevations	O
+on	O
+the	O
+global	O
+severity	O
+index	O
+of	O
+the	O
+Symptom	O
+Checklist	O
+-	O
+90	O
+and	O
+elevations	O
+on	O
+somatization	O
+,	O
+obsessive	O
+compulsive	O
+,	O
+interpersonal	O
+sensitivity	O
+,	O
+depression	O
+,	O
+anxiety	O
+and	O
+psychoticism	O
+subscales	O
+.	O
+
+Chronic	O
+administration	O
+of	O
+sodium	O
+cyanate	O
+decreases	O
+O2	O
+extraction	O
+ratio	O
+in	O
+dogs	O
+.	O
+
+Nucleotide	O
+sequencing	O
+indicates	O
+that	O
+this	O
+E1	B-GENE
+alpha	I-GENE
+cDNA	I-GENE
+clone	O
+is	O
+1821	O
+base	O
+pairs	O
+(	O
+bp	O
+)	O
+in	O
+length	O
+with	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+1365	O
+bp	O
+and	O
+a	O
+3	O
+'	O
+-	O
+untranslated	O
+region	O
+of	O
+356	O
+bp	O
+.	O
+
+SPA	O
+from	O
+PAG	O
+sites	O
+was	O
+associated	O
+with	O
+aversion	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+MAN	O
+showed	O
+a	O
+unimodal	O
+,	O
+skewed	O
+distribution	O
+,	O
+with	O
+a	O
+range	O
+from	O
+approximately	O
+1	O
+to	O
+14	O
+micron	O
+and	O
+a	O
+maximum	O
+at	O
+3	O
+-	O
+4	O
+micron	O
+.	O
+
+Abnormal	O
+technetium	O
+Tc	O
+99m	O
+medronate	O
+scans	O
+in	O
+patients	O
+with	O
+previously	O
+undiagnosed	O
+polyarthralgias	O
+suggested	O
+inflammatory	O
+arthropathy	O
+and	O
+influenced	O
+management	O
+decisions	O
+with	O
+favorable	O
+therapeutic	O
+outcomes	O
+.	O
+
+Practical	O
+interest	O
+of	O
+such	O
+studies	O
+is	O
+limited	O
+since	O
+the	O
+pharmacokinetic	O
+parameters	O
+are	O
+systematically	O
+evaluated	O
+in	O
+man	O
+during	O
+phase	O
+I	O
+trials	O
+.	O
+
+The	O
+artery	O
+cuff	O
+was	O
+slightly	O
+superior	O
+to	O
+the	O
+fat	O
+wrap	O
+,	O
+particularly	O
+in	O
+having	O
+fewer	O
+adhesions	O
+and	O
+a	O
+better	O
+histological	O
+picture	O
+.	O
+
+Lithium	O
+-	O
+carbonate	O
+action	O
+during	O
+radiation	O
+therapy	O
+has	O
+been	O
+studied	O
+,	O
+valuing	O
+the	O
+positive	O
+effect	O
+on	O
+leukopoiesis	O
+and	O
+the	O
+consequent	O
+better	O
+clinical	O
+conditions	O
+of	O
+the	O
+patients	O
+in	O
+course	O
+of	O
+treatment	O
+.	O
+
+Of	O
+the	O
+53	O
+units	O
+tested	O
+during	O
+sinusoidal	O
+motion	O
+at	O
+0	O
+.	O
+05	O
+Hz	O
+(	O
+9	O
+.	O
+1	O
+cm	O
+/	O
+s	O
+)	O
+,	O
+1	O
+(	O
+1	O
+.	O
+9	O
+%	O
+)	O
+was	O
+responsive	O
+to	O
+the	O
+otolith	O
+input	O
+only	O
+,	O
+13	O
+(	O
+24	O
+.	O
+5	O
+%	O
+)	O
+were	O
+influenced	O
+by	O
+the	O
+visual	O
+input	O
+only	O
+and	O
+23	O
+(	O
+43	O
+.	O
+4	O
+%	O
+)	O
+responded	O
+to	O
+both	O
+modalities	O
+.	O
+
+Electroglottography	O
+is	O
+a	O
+useful	O
+,	O
+non	O
+-	O
+invasive	O
+technique	O
+that	O
+can	O
+assist	O
+in	O
+the	O
+assessment	O
+of	O
+vocal	O
+fold	O
+dysfunction	O
+.	O
+
+Statistical	O
+analysis	O
+of	O
+the	O
+degrees	O
+of	O
+secondary	O
+spinal	O
+cord	O
+compression	O
+was	O
+performed	O
+in	O
+group	O
+-	O
+1	O
+dogs	O
+by	O
+measuring	O
+and	O
+comparing	O
+ratios	O
+of	O
+the	O
+vertical	O
+to	O
+the	O
+horizontal	O
+diameters	O
+of	O
+the	O
+transverse	O
+spinal	O
+cord	O
+sections	O
+from	O
+locations	O
+within	O
+(	O
+T12	O
+to	O
+L1	O
+)	O
+and	O
+out	O
+of	O
+(	O
+T11	O
+,	O
+T11	O
+-	O
+12	O
+,	O
+L1	O
+-	O
+2	O
+,	O
+and	O
+L2	O
+)	O
+the	O
+region	O
+of	O
+surgical	O
+intervention	O
+.	O
+
+The	O
+pharmacological	O
+effects	O
+of	O
+the	O
+novel	O
+compound	O
+WEB	O
+1881	O
+FU	O
+(	O
+4	O
+-	O
+amino	O
+-	O
+methyl	O
+-	O
+1	O
+-	O
+benzyl	O
+-	O
+pyrrolidine	O
+-	O
+2	O
+-	O
+one	O
+-	O
+fumarate	O
+)	O
+were	O
+investigated	O
+.	O
+
+Histopathological	O
+examination	O
+revealed	O
+dose	O
+-	O
+related	O
+proliferation	O
+of	O
+type	O
+II	O
+pneumocytes	O
+in	O
+dams	O
+and	O
+proliferation	O
+of	O
+interstitial	O
+cells	O
+and	O
+delayed	O
+septal	O
+/	O
+capillary	O
+development	O
+in	O
+neonates	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+So	O
+far	O
+no	O
+problems	O
+with	O
+multiply	O
+resistant	O
+strains	O
+have	O
+developed	O
+.	O
+
+The	O
+state	O
+of	O
+the	O
+liver	O
+in	O
+generalized	O
+forms	O
+of	O
+meningococcal	O
+infection	O
+
+The	O
+effects	O
+produced	O
+by	O
+oral	O
+administration	O
+of	O
+500	O
+mg	O
+/	O
+kg	O
+p	O
+-	O
+xylene	O
+or	O
+toluene	O
+lasted	O
+at	O
+least	O
+8	O
+hr	O
+,	O
+while	O
+the	O
+effect	O
+of	O
+inhaled	O
+p	O
+-	O
+xylene	O
+dissipated	O
+within	O
+75	O
+min	O
+of	O
+removal	O
+from	O
+the	O
+exposure	O
+.	O
+
+Thin	O
+melanomas	O
+can	O
+metastasize	O
+and	O
+be	O
+lethal	O
+.	O
+
+The	O
+TA	O
+muscle	O
+was	O
+fatigued	O
+by	O
+four	O
+forms	O
+of	O
+repeated	O
+isometric	O
+contractions	O
+:	O
+(	O
+1	O
+)	O
+maximal	O
+voluntary	O
+contractions	O
+(	O
+MVC	O
+)	O
+,	O
+(	O
+2	O
+)	O
+MVC	O
+with	O
+circulation	O
+occluded	O
+,	O
+(	O
+3	O
+)	O
+electrically	O
+evoked	O
+contractions	O
+with	O
+20	O
+Hz	O
+supramaximal	O
+voltage	O
+stimulation	O
+and	O
+(	O
+4	O
+)	O
+electrically	O
+evoked	O
+contractions	O
+with	O
+circulation	O
+occluded	O
+.	O
+
+The	O
+actuarial	O
+local	O
+control	O
+rates	O
+at	O
+10	O
+years	O
+for	O
+the	O
+three	O
+treatment	O
+groups	O
+were	O
+as	O
+follows	O
+:	O
+subtotal	O
+excision	O
+alone	O
+,	O
+18	O
+%	O
+;	O
+subtotal	O
+excision	O
+plus	O
+postoperative	O
+radiation	O
+therapy	O
+,	O
+82	O
+%	O
+;	O
+and	O
+total	O
+excision	O
+alone	O
+,	O
+77	O
+%	O
+.	O
+
+The	O
+effects	O
+of	O
+anabolic	O
+implants	O
+on	O
+rate	O
+,	O
+composition	O
+and	O
+energetic	O
+efficiency	O
+of	O
+growth	O
+were	O
+determined	O
+in	O
+steers	O
+fed	O
+diets	O
+varying	O
+in	O
+forage	O
+and	O
+grain	O
+content	O
+.	O
+
+Prolonged	O
+suspension	O
+induced	O
+a	O
+significant	O
+change	O
+in	O
+the	O
+geometric	O
+configuration	O
+of	O
+the	O
+femur	O
+middiaphysis	O
+by	O
+increasing	O
+the	O
+minimum	O
+diameter	O
+(	O
+12	O
+%	O
+)	O
+without	O
+any	O
+significant	O
+alterations	O
+in	O
+cortical	O
+area	O
+,	O
+density	O
+,	O
+mineral	O
+,	O
+and	O
+collagen	B-GENE
+concentrations	O
+.	O
+
+Thyroid	O
+function	O
+tests	O
+were	O
+performed	O
+on	O
+300	O
+admissions	O
+,	O
+leaving	O
+707	O
+untested	O
+.	O
+
+Data	O
+on	O
+the	O
+line	O
+spread	O
+function	O
+(	O
+LSF	O
+)	O
+were	O
+obtained	O
+from	O
+the	O
+image	O
+of	O
+a	O
+0	O
+.	O
+2	O
+mm	O
+wide	O
+slit	O
+between	O
+tungsten	O
+blocks	O
+that	O
+were	O
+positioned	O
+at	O
+the	O
+isocentre	O
+in	O
+front	O
+of	O
+a	O
+polystyrene	O
+phantom	O
+.	O
+
+Primary	O
+infection	O
+is	O
+usually	O
+managed	O
+conservatively	O
+.	O
+
+Papers	O
+of	O
+the	O
+Society	O
+for	O
+Clinical	O
+Vascular	O
+Surgery	O
+.	O
+
+Prognosis	O
+in	O
+Bowen	O
+'	O
+s	O
+disease	O
+localized	O
+to	O
+the	O
+ano	O
+-	O
+genital	O
+region	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+results	O
+suggest	O
+that	O
+chlorphentermine	O
+may	O
+be	O
+capable	O
+of	O
+producing	O
+dual	O
+stimulus	O
+effects	O
+in	O
+animals	O
+.	O
+
+These	O
+findings	O
+indicate	O
+that	O
+autophosphorylation	O
+of	O
+Thr286	O
+(	O
+alpha	O
+subunit	O
+)	O
+and	O
+Thr287	O
+(	O
+beta	O
+subunit	O
+)	O
+is	O
+responsible	O
+for	O
+transition	O
+of	O
+CaM	B-GENE
+-	I-GENE
+kinase	I-GENE
+II	I-GENE
+to	O
+the	O
+Ca2	O
++	O
+-	O
+independent	O
+form	O
+.	O
+
+This	O
+rapid	O
+and	O
+extensive	O
+penetration	O
+of	O
+intrathecally	O
+administered	O
+chemotherapy	O
+may	O
+offer	O
+insight	O
+into	O
+the	O
+myelopathy	O
+observed	O
+with	O
+these	O
+treatments	O
+.	O
+
+The	O
+interaction	O
+of	O
+radiation	O
+and	O
+hyperthermia	O
+was	O
+systematically	O
+studied	O
+in	O
+the	O
+Dunning	O
+R3327G	O
+prostatic	O
+adenocarcinoma	O
+,	O
+the	O
+preeminent	O
+animal	O
+model	O
+for	O
+human	O
+prostatic	O
+cancer	O
+.	O
+
+Pregnant	O
+rats	O
+were	O
+exposed	O
+to	O
+one	O
+of	O
+the	O
+following	O
+:	O
+(	O
+1	O
+)	O
+10	O
+%	O
+O2	O
+in	O
+N2	O
+or	O
+100	O
+%	O
+O2	O
+for	O
+2	O
+days	O
+beginning	O
+at	O
+day	O
+7	O
+,	O
+11	O
+,	O
+14	O
+,	O
+or	O
+18	O
+of	O
+pregnancy	O
+;	O
+(	O
+2	O
+)	O
+10	O
+%	O
+O2	O
+in	O
+N2	O
+or	O
+100	O
+%	O
+O2	O
+for	O
+10	O
+h	O
+/	O
+day	O
+beginning	O
+at	O
+day	O
+7	O
+;	O
+or	O
+(	O
+3	O
+)	O
+14	O
+-	O
+11	O
+%	O
+O2	O
+in	O
+N2	O
+continuously	O
+beginning	O
+at	O
+day	O
+14	O
+till	O
+day	O
+21	O
+when	O
+they	O
+were	O
+sacrificed	O
+.	O
+
+Seven	O
+patients	O
+(	O
+8	O
+.	O
+3	O
+percent	O
+)	O
+had	O
+latent	O
+hypothyroidism	O
+only	O
+discovered	O
+by	O
+hormonal	O
+determinations	O
+.	O
+
+Addition	O
+of	O
+sucralfate	O
+or	O
+De	O
+-	O
+Nol	O
+resulted	O
+in	O
+increments	O
+of	O
+gastric	O
+HCO3	O
+secretion	O
+,	O
+reaching	O
+about	O
+45	O
+%	O
+and	O
+59	O
+%	O
+,	O
+respectively	O
+,	O
+of	O
+the	O
+maximal	O
+HCO3	O
+response	O
+to	O
+16	O
+,	O
+16	O
+-	O
+dimethyl	O
+PGE2	O
+(	O
+dmPGE2	O
+)	O
+.	O
+
+Moreover	O
+,	O
+unlike	O
+control	O
+rats	O
+operated	O
+animals	O
+did	O
+not	O
+show	O
+aversion	O
+to	O
+the	O
+highest	O
+concentrations	O
+of	O
+saccharin	O
+solutions	O
+.	O
+
+In	O
+Salmo	O
+gairdneri	O
+,	O
+no	O
+specialized	O
+system	O
+of	O
+portal	O
+vessels	O
+appears	O
+to	O
+exist	O
+between	O
+the	O
+pineal	O
+organ	O
+and	O
+other	O
+portions	O
+of	O
+the	O
+brain	O
+.	O
+
+Nuclear	B-GENE
+factor	I-GENE
+III	I-GENE
+(	O
+NFIII	B-GENE
+)	O
+is	O
+a	O
+protein	O
+from	O
+HeLa	O
+cells	O
+that	O
+stimulates	O
+the	O
+initiation	O
+of	O
+adenovirus	O
+type	O
+2	O
+(	O
+Ad2	O
+)	O
+DNA	O
+replication	O
+by	O
+binding	O
+to	O
+a	O
+specific	O
+nucleotide	O
+sequence	O
+in	O
+the	O
+origin	O
+,	O
+adjacent	O
+to	O
+the	O
+nuclear	B-GENE
+factor	I-GENE
+I	I-GENE
+recognition	I-GENE
+site	I-GENE
+.	O
+
+We	O
+conclude	O
+that	O
+cephalothin	O
+clearance	O
+of	O
+S	O
+.	O
+aureus	O
+from	O
+a	O
+site	O
+accessible	O
+to	O
+phagocytes	O
+was	O
+delayed	O
+when	O
+compared	O
+to	O
+a	O
+phagocyte	O
+-	O
+inaccessible	O
+site	O
+.	O
+
+The	O
+findings	O
+are	O
+discussed	O
+in	O
+the	O
+context	O
+of	O
+known	O
+properties	O
+of	O
+cortical	O
+-	O
+bar	O
+detectors	O
+.	O
+
+Mean	O
+rCBF	O
+increased	O
+in	O
+some	O
+patients	O
+4	O
+-	O
+8	O
+weeks	O
+after	O
+surgery	O
+on	O
+the	O
+ipsilateral	O
+side	O
+.	O
+
+Quantitative	O
+computed	O
+tomography	O
+for	O
+measuring	O
+vertebral	O
+bone	O
+mineral	O
+content	O
+offers	O
+high	O
+sensitivity	O
+and	O
+reproducibility	O
+.	O
+
+The	O
+structure	O
+of	O
+the	O
+enhancer	O
+was	O
+also	O
+probed	O
+by	O
+inserting	O
+a	O
+pair	O
+of	O
+complementary	O
+synthetic	O
+oligodeoxynucleotides	O
+which	O
+represented	O
+the	O
+region	O
+between	O
+nt	O
+positions	O
+-	O
+235	O
+and	O
+-	O
+215	O
+into	O
+a	O
+truncated	O
+template	O
+which	O
+lacked	O
+the	O
+enhancer	O
+.	O
+
+Kf	O
+,	O
+c	O
+and	O
+CT	O
+(	O
+referenced	O
+to	O
+the	O
+initial	O
+lung	O
+mass	O
+)	O
+decreased	O
+linearly	O
+with	O
+reductions	O
+in	O
+lung	O
+mass	O
+%	O
+delta	O
+Kf	O
+,	O
+c	O
+=	O
+1	O
+.	O
+26	O
+-	O
+0	O
+.	O
+98	O
+%	O
+mass	O
+removed	O
+(	O
+r	O
+=	O
+0	O
+.	O
+90	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+and	O
+%	O
+delta	O
+CT	O
+=	O
+-	O
+3	O
+.	O
+99	O
+-	O
+0	O
+.	O
+98	O
+%	O
+mass	O
+removed	O
+(	O
+r	O
+=	O
+0	O
+.	O
+82	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+relationships	O
+that	O
+were	O
+not	O
+altered	O
+by	O
+blocker	O
+pretreatment	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Two	O
+scintigraphic	O
+methods	O
+,	O
+resting	O
+dipyridamole	O
+and	O
+exercise	O
+thallium	O
+-	O
+201	O
+myocardial	O
+perfusion	O
+imaging	O
+,	O
+to	O
+detect	O
+and	O
+localize	O
+coronary	O
+artery	O
+stenosis	O
+were	O
+compared	O
+in	O
+32	O
+patients	O
+suffering	O
+from	O
+coronary	O
+artery	O
+disease	O
+.	O
+
+From	O
+these	O
+results	O
+,	O
+it	O
+is	O
+concluded	O
+that	O
+EDLF	O
+has	O
+clear	O
+vasoconstrictor	O
+properties	O
+which	O
+are	O
+not	O
+due	O
+to	O
+adrenergic	O
+or	O
+calcium	O
+entry	O
+mechanisms	O
+and	O
+that	O
+there	O
+are	O
+differences	O
+in	O
+the	O
+vasoconstrictor	O
+effects	O
+of	O
+EDLFs	O
+with	O
+respect	O
+to	O
+different	O
+vascular	O
+beds	O
+.	O
+
+Research	O
+was	O
+carried	O
+out	O
+on	O
+the	O
+rheumatoid	B-GENE
+factors	I-GENE
+in	O
+the	O
+serum	O
+of	O
+917	O
+patients	O
+by	O
+means	O
+of	O
+two	O
+tests	O
+(	O
+one	O
+using	O
+polystyrene	O
+and	O
+one	O
+with	O
+erythrocytes	O
+)	O
+and	O
+the	O
+results	O
+obtained	O
+were	O
+compared	O
+using	O
+a	O
+method	O
+of	O
+reference	O
+.	O
+
+A	O
+low	O
+aspirin	B-GENE
+esterase	I-GENE
+activity	O
+may	O
+be	O
+a	O
+contributory	O
+factor	O
+in	O
+precipitating	O
+these	O
+aspirin	O
+sensitive	O
+reactions	O
+.	O
+
+In	O
+both	O
+experiments	O
+,	O
+average	O
+daily	O
+gain	O
+and	O
+gain	O
+-	O
+to	O
+-	O
+feed	O
+ratio	O
+were	O
+similar	O
+for	O
+TR	O
+and	O
+CR	O
+.	O
+
+Overall	O
+least	O
+-	O
+squares	O
+means	O
+for	O
+uncooked	O
+and	O
+cooked	O
+longissimus	O
+muscle	O
+and	O
+subcutaneous	O
+fat	O
+were	O
+63	O
+.	O
+32	O
+,	O
+80	O
+.	O
+27	O
+and	O
+98	O
+.	O
+90	O
+mg	O
+of	O
+cholesterol	O
+/	O
+100	O
+g	O
+of	O
+tissue	O
+,	O
+respectively	O
+.	O
+
+The	O
+role	O
+of	O
+supercritical	O
+fluid	O
+chromatography	O
+(	O
+SFC	O
+)	O
+as	O
+a	O
+viable	O
+technique	O
+for	O
+analyzing	O
+agricultural	O
+products	O
+has	O
+been	O
+investigated	O
+using	O
+packed	O
+and	O
+capillary	O
+column	O
+methodology	O
+.	O
+
+Nitrofurazone	O
+significantly	O
+reduced	O
+the	O
+rise	O
+in	O
+LH	B-GENE
+induced	O
+by	O
+LHRH	B-GENE
+.	O
+
+Ovarian	O
+tumors	O
+in	O
+pregnancy	O
+.	O
+
+Ultrastructural	O
+study	O
+of	O
+polyarteritis	O
+
+X2	O
+test	O
+,	O
+with	O
+Yates	O
+correction	O
+if	O
+need	O
+,	O
+was	O
+used	O
+as	O
+statistical	O
+.	O
+method	O
+.	O
+
+After	O
+a	O
+baseline	O
+study	O
+,	O
+WPW	O
+syndrome	O
+was	O
+simulated	O
+by	O
+stimulation	O
+at	O
+seven	O
+different	O
+sites	O
+around	O
+the	O
+base	O
+of	O
+the	O
+ventricles	O
+,	O
+and	O
+RNV	O
+'	O
+s	O
+were	O
+obtained	O
+.	O
+
+All	O
+patients	O
+had	O
+the	O
+CA	B-GENE
+125	I-GENE
+assay	O
+performed	O
+within	O
+one	O
+week	O
+before	O
+their	O
+second	O
+-	O
+look	O
+operation	O
+.	O
+
+Allergy	O
+and	O
+Tourette	O
+'	O
+s	O
+syndrome	O
+.	O
+
+The	O
+criterion	O
+was	O
+reached	O
+after	O
+two	O
+sessions	O
+and	O
+generalization	O
+to	O
+a	O
+variety	O
+of	O
+pills	O
+and	O
+capsules	O
+occurred	O
+.	O
+
+Clinical	O
+method	O
+for	O
+the	O
+treatment	O
+of	O
+Class	O
+II	O
+occlusal	O
+anomalies	O
+with	O
+open	O
+bite	O
+
+Enoxacin	O
+appears	O
+to	O
+be	O
+well	O
+suited	O
+for	O
+the	O
+treatment	O
+of	O
+complicated	O
+UTI	O
+.	O
+
+An	O
+industry	O
+-	O
+wide	O
+retrospective	O
+cohort	O
+mortality	O
+study	O
+was	O
+conducted	O
+on	O
+6	O
+,	O
+152	O
+chemical	O
+workers	O
+(	O
+2	O
+,	O
+460	O
+exposed	O
+and	O
+3	O
+,	O
+692	O
+nonexposed	O
+)	O
+engaged	O
+in	O
+chloromethyl	O
+ether	O
+manufacture	O
+at	O
+7	O
+major	O
+U	O
+.	O
+S	O
+.	O
+companies	O
+between	O
+1948	O
+and	O
+1980	O
+.	O
+
+The	O
+diagnosis	O
+of	O
+amyloidosis	O
+was	O
+determined	O
+from	O
+a	O
+labial	O
+salivary	O
+gland	O
+biopsy	O
+.	O
+
+Hair	O
+and	O
+blood	O
+samples	O
+were	O
+taken	O
+before	O
+vitamin	O
+C	O
+or	O
+placebo	O
+supplementation	O
+was	O
+started	O
+and	O
+at	O
+monthly	O
+intervals	O
+thereafter	O
+for	O
+three	O
+months	O
+.	O
+
+In	O
+treated	O
+herds	O
+,	O
+cows	O
+more	O
+than	O
+40	O
+d	O
+postpartum	O
+with	O
+a	O
+corpus	O
+luteum	O
+received	O
+prostaglandin	O
+F2	O
+alpha	O
+.	O
+
+Emergency	O
+treatment	O
+of	O
+facial	O
+and	O
+maxillary	O
+/	O
+mandibular	O
+injuries	O
+
+In	O
+14	O
+cases	O
+,	O
+isolates	O
+were	O
+biotyped	O
+yielding	O
+eight	O
+with	O
+biotype	O
+II	O
+,	O
+four	O
+with	O
+biotype	O
+III	O
+,	O
+and	O
+one	O
+each	O
+with	O
+biotypes	O
+IV	O
+and	O
+V	O
+.	O
+
+A	O
+total	O
+of	O
+117	O
+EVS	O
+treatments	O
+were	O
+performed	O
+on	O
+34	O
+patients	O
+.	O
+
+Most	O
+of	O
+the	O
+prepeptide	O
+portion	O
+of	O
+the	O
+precursor	O
+polypeptide	O
+is	O
+encoded	O
+by	O
+the	O
+next	O
+three	O
+exons	O
+,	O
+and	O
+the	O
+mature	O
+form	O
+of	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+is	O
+encoded	O
+by	O
+the	O
+remaining	O
+three	O
+exons	O
+.	O
+
+A	O
+stochastic	O
+version	O
+of	O
+Kernell	O
+'	O
+s	O
+(	O
+1968	O
+,	O
+1972	O
+)	O
+model	O
+with	O
+cumulative	O
+afterhyperpolarization	O
+(	O
+AHP	O
+)	O
+was	O
+simulated	O
+.	O
+
+In	O
+a	O
+previous	O
+interim	O
+report	O
+we	O
+noted	O
+more	O
+prompt	O
+resolution	O
+of	O
+dermatomal	O
+signs	O
+and	O
+symptoms	O
+with	O
+acyclovir	O
+treatment	O
+.	O
+
+The	O
+detectability	O
+of	O
+the	O
+defects	O
+in	O
+RCA	O
+or	O
+LAD	O
+region	O
+was	O
+80	O
+%	O
+in	O
+single	O
+-	O
+position	O
+scans	O
+in	O
+stress	O
+studies	O
+.	O
+
+Pharmacologic	O
+properties	O
+of	O
+serotonergic	O
+agents	O
+and	O
+antidepressant	O
+drugs	O
+.	O
+
+This	O
+brief	O
+hypercapnic	O
+challenge	O
+induced	O
+a	O
+rapid	O
+increase	O
+in	O
+CBF	O
+in	O
+the	O
+absence	O
+of	O
+any	O
+change	O
+in	O
+MABP	O
+.	O
+
+Osteocalcin	B-GENE
+(	O
+serum	B-GENE
+bone	I-GENE
+-	I-GENE
+Gla	I-GENE
+protein	I-GENE
+,	O
+sBGP	B-GENE
+)	O
+,	O
+serum	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+(	O
+sAP	B-GENE
+)	O
+and	O
+urinary	O
+hydroxyproline	O
+/	O
+creatinine	O
+ratio	O
+(	O
+uOH	O
+-	O
+Prol	O
+/	O
+creatinine	O
+)	O
+have	O
+been	O
+measured	O
+in	O
+21	O
+patients	O
+with	O
+primary	O
+hyperparathyroidism	O
+(	O
+PHPT	O
+)	O
+and	O
+in	O
+nine	O
+patients	O
+with	O
+hypercalcaemia	O
+of	O
+malignancy	O
+(	O
+HM	O
+)	O
+.	O
+
+Multivariate	O
+logistic	O
+regression	O
+analysis	O
+indicated	O
+that	O
+seropositivity	O
+was	O
+strongly	O
+associated	O
+with	O
+the	O
+prevalence	O
+of	O
+hepatitis	O
+B	O
+in	O
+an	O
+employee	O
+'	O
+s	O
+country	O
+of	O
+birth	O
+and	O
+with	O
+age	O
+.	O
+
+Hexsyn	O
+is	O
+the	O
+Goodyear	O
+Tire	O
+and	O
+Rubber	O
+Company	O
+tradename	O
+for	O
+a	O
+polyolefin	O
+rubber	O
+synthesized	O
+from	O
+1	O
+-	O
+hexene	O
+with	O
+3	O
+-	O
+5	O
+%	O
+methylhexadiene	O
+as	O
+the	O
+source	O
+of	O
+residual	O
+double	O
+bonds	O
+for	O
+vulcanization	O
+.	O
+
+Chimeric	O
+phage	O
+-	O
+plasmid	O
+expression	O
+vectors	O
+were	O
+constructed	O
+from	O
+pUC18	O
+/	O
+19	O
+plasmids	O
+by	O
+cloning	O
+a	O
+single	O
+-	O
+stranded	O
+DNA	O
+(	O
+ssDNA	O
+)	O
+origin	O
+of	O
+replication	O
+from	O
+bacteriophage	O
+f1	O
+and	O
+inserting	O
+a	O
+bacteriophage	O
+T7	O
+promoter	O
+within	O
+the	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+gene	I-GENE
+.	O
+
+By	O
+order	O
+of	O
+decreasing	O
+rate	O
+,	O
+finger	O
+flexors	O
+,	O
+jaw	O
+,	O
+crossed	O
+adductors	O
+,	O
+and	O
+triceps	O
+reflexes	O
+were	O
+less	O
+frequently	O
+elicited	O
+in	O
+both	O
+groups	O
+.	O
+
+Natl	O
+.	O
+
+Five	O
+out	O
+of	O
+eight	O
+consecutive	O
+cases	O
+with	O
+initial	O
+symptoms	O
+of	O
+a	O
+'	O
+midline	O
+granuloma	O
+'	O
+were	O
+identified	O
+as	O
+malignant	O
+histiocytosis	O
+(	O
+histiocytic	O
+sarcoma	O
+)	O
+which	O
+within	O
+5	O
+months	O
+to	O
+4	O
+years	O
+led	O
+to	O
+generalization	O
+and	O
+death	O
+.	O
+
+All	O
+patients	O
+then	O
+received	O
+suxamethonium	O
+1	O
+.	O
+5	O
+mg	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+v	O
+.	O
+
+The	O
+highest	O
+postoperative	O
+CK	B-GENE
+-	I-GENE
+MB	I-GENE
+level	O
+was	O
+less	O
+after	O
+BC	O
+(	O
+BC	O
+,	O
+31	O
++	O
+/	O
+-	O
+17	O
+U	O
+/	O
+L	O
+;	O
+CC	O
+,	O
+56	O
++	O
+/	O
+-	O
+13	O
+U	O
+/	O
+L	O
+;	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+No	O
+relevant	O
+changes	O
+in	O
+heart	O
+rate	O
+,	O
+body	O
+weight	O
+,	O
+and	O
+plasma	O
+levels	O
+of	O
+renin	B-GENE
+activity	O
+and	O
+aldosterone	O
+concentration	O
+were	O
+observed	O
+.	O
+
+High	O
+trough	O
+serum	O
+TOB	O
+concentrations	O
+were	O
+associated	O
+with	O
+death	O
+and	O
+very	O
+low	O
+levels	O
+with	O
+recovery	O
+.	O
+
+State	O
+-	O
+approved	O
+schools	O
+of	O
+nursing	O
+R	O
+.	O
+N	O
+.	O
+
+In	O
+a	O
+maxicell	O
+system	O
+a	O
+protein	O
+with	O
+an	O
+approximate	O
+molecular	O
+weight	O
+of	O
+36	O
+,	O
+000	O
+was	O
+synthesized	O
+.	O
+
+The	O
+incidence	O
+of	O
+second	O
+malignant	O
+neoplasms	O
+was	O
+lower	O
+(	O
+1	O
+.	O
+3	O
+%	O
+)	O
+in	O
+the	O
+group	O
+treated	O
+with	O
+5	O
+-	O
+fluorouracil	O
+,	O
+doxorubicin	O
+,	O
+and	O
+cyclophosphamide	O
+than	O
+in	O
+the	O
+historical	O
+control	O
+group	O
+(	O
+4	O
+.	O
+8	O
+%	O
+)	O
+.	O
+
+Ovulation	O
+was	O
+induced	O
+in	O
+8	O
+(	O
+56	O
+.	O
+7	O
+%	O
+)	O
+patients	O
+who	O
+conceived	O
+.	O
+
+In	O
+previous	O
+work	O
+(	O
+E	O
+.	O
+
+The	O
+small	O
+size	O
+and	O
+placement	O
+of	O
+the	O
+mutagenesis	O
+marker	O
+(	O
+the	O
+supF	B-GENE
+suppressor	I-GENE
+tRNA	I-GENE
+gene	I-GENE
+from	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+)	O
+within	O
+the	O
+vector	O
+substantially	O
+reduced	O
+the	O
+frequency	O
+of	O
+spontaneous	O
+mutations	O
+normally	O
+observed	O
+after	O
+transfection	O
+of	O
+mammalian	O
+cells	O
+with	O
+plasmid	O
+DNA	O
+;	O
+hence	O
+,	O
+UV	O
+-	O
+induced	O
+mutations	O
+were	O
+easily	O
+identified	O
+above	O
+the	O
+spontaneous	O
+background	O
+.	O
+
+W	O
+.	O
+
+Tetrad	O
+analysis	O
+and	O
+mitotic	O
+recombination	O
+experiments	O
+localized	O
+the	O
+PEP4	B-GENE
+gene	I-GENE
+proximal	O
+to	O
+GAL4	B-GENE
+on	O
+chromosome	O
+XVI	O
+.	O
+
+Based	O
+on	O
+our	O
+observations	O
+,	O
+we	O
+propose	O
+a	O
+model	O
+whereby	O
+inactive	O
+precursor	O
+molecules	O
+produced	O
+from	O
+the	O
+PEP4	B-GENE
+gene	I-GENE
+self	O
+-	O
+activate	O
+within	O
+the	O
+yeast	O
+vacuole	O
+and	O
+subsequently	O
+activate	O
+other	O
+vacuolar	B-GENE
+hydrolases	I-GENE
+.	O
+
+In	O
+vitro	O
+translation	O
+of	O
+RNA	O
+synthesized	O
+from	O
+the	O
+cloned	O
+cDNAs	O
+predicts	O
+that	O
+P0	B-GENE
+transcripts	I-GENE
+are	O
+translated	O
+into	O
+a	O
+novel	O
+12	O
+.	O
+5	O
+-	O
+kilodalton	O
+protein	O
+corresponding	O
+to	O
+the	O
+first	O
+open	O
+reading	O
+frame	O
+.	O
+
+The	O
+N	O
+-	O
+terminal	O
+amino	O
+acid	O
+sequence	O
+of	O
+Mop	B-GENE
+has	O
+sequence	O
+homology	O
+with	O
+DNA	O
+binding	O
+proteins	O
+.	O
+
+Several	O
+new	O
+techniques	O
+are	O
+available	O
+for	O
+monitoring	O
+control	O
+of	O
+diabetes	O
+.	O
+
+Ciprofloxacin	O
+:	O
+an	O
+overview	O
+of	O
+adverse	O
+experiences	O
+.	O
+
+The	O
+rho	B-GENE
+genes	I-GENE
+comprise	O
+an	O
+evolutionarily	O
+conserved	O
+family	O
+with	O
+significant	O
+homology	O
+to	O
+the	O
+ras	B-GENE
+oncogene	I-GENE
+family	I-GENE
+.	O
+
+Also	O
+,	O
+component	O
+I	O
+significantly	O
+correlated	O
+with	O
+fasting	O
+insulin	B-GENE
+and	O
+VO2	O
+max	O
+for	O
+both	O
+sexes	O
+and	O
+with	O
+basal	O
+metabolism	O
+and	O
+HDL	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+for	O
+females	O
+and	O
+males	O
+,	O
+respectively	O
+.	O
+
+The	O
+glucose	O
+areas	O
+following	O
+the	O
+ingestion	O
+of	O
+the	O
+foods	O
+were	O
+:	O
+Study	O
+1	O
+:	O
+glucose	O
+11	O
+.	O
+7	O
+,	O
+orange	O
+juice	O
+7	O
+.	O
+3	O
+,	O
+sucrose	O
+5	O
+.	O
+2	O
+,	O
+glucose	O
++	O
+fructose	O
+6	O
+.	O
+3	O
+,	O
+and	O
+fructose	O
+0	O
+.	O
+7	O
+mmol	O
+X	O
+h	O
+/	O
+l	O
+;	O
+Study	O
+2	O
+:	O
+glucose	O
+14	O
+.	O
+6	O
+,	O
+orange	O
+juice	O
+7	O
+.	O
+3	O
+,	O
+apples	O
+5	O
+.	O
+5	O
+,	O
+and	O
+apple	O
+juice	O
+4	O
+.	O
+7	O
+mmol	O
+X	O
+h	O
+/	O
+l	O
+;	O
+Study	O
+3	O
+:	O
+glucose	O
+12	O
+.	O
+6	O
+,	O
+ice	O
+cream	O
+8	O
+.	O
+1	O
+,	O
+milk	O
+3	O
+.	O
+7	O
+,	O
+and	O
+lactose	O
+4	O
+.	O
+1	O
+mmol	O
+X	O
+h	O
+/	O
+l	O
+.	O
+
+The	O
+serum	B-GENE
+insulin	I-GENE
+response	O
+cannot	O
+.	O
+
+SCL	O
+prolonged	O
+promptly	O
+after	O
+verapamil	O
+,	O
+and	O
+sinus	O
+arrest	O
+developed	O
+in	O
+two	O
+of	O
+10	O
+group	O
+2	O
+and	O
+two	O
+of	O
+five	O
+group	O
+3	O
+animals	O
+.	O
+
+Postglucose	O
+serum	B-GENE
+insulin	I-GENE
+levels	O
+showed	O
+no	O
+significant	O
+correlations	O
+with	O
+systolic	O
+or	O
+diastolic	O
+blood	O
+pressure	O
+levels	O
+in	O
+men	O
+,	O
+but	O
+in	O
+female	O
+diabetic	O
+and	O
+non	O
+-	O
+diabetic	O
+subjects	O
+significant	O
+correlations	O
+were	O
+found	O
+in	O
+particular	O
+with	O
+systolic	O
+blood	O
+pressure	O
+level	O
+.	O
+
+We	O
+used	O
+oligonucleotide	O
+-	O
+directed	O
+mutagenesis	O
+to	O
+alter	O
+a	O
+site	O
+in	O
+MucA	B-GENE
+homologous	O
+to	O
+the	O
+Ala	O
+-	O
+Gly	O
+cleavage	O
+site	O
+of	O
+LexA	B-GENE
+.	O
+
+The	O
+latter	O
+was	O
+determined	O
+as	O
+follows	O
+:	O
+Type	O
+I	O
+-	O
+solid	O
+tumor	O
+tissue	O
+without	O
+significant	O
+peripheral	O
+isolated	O
+tumor	O
+cells	O
+;	O
+Type	O
+II	O
+-	O
+solid	O
+tumor	O
+tissue	O
+associated	O
+with	O
+peripheral	O
+isolated	O
+tumor	O
+cells	O
+;	O
+Type	O
+III	O
+-	O
+isolated	O
+tumor	O
+cells	O
+only	O
+.	O
+
+The	O
+pharmacology	O
+of	O
+carnitine	O
+.	O
+
+Acute	O
+inhalation	O
+toxicity	O
+of	O
+T	O
+-	O
+2	O
+mycotoxin	O
+in	O
+mice	O
+.	O
+
+The	O
+present	O
+investigation	O
+sought	O
+to	O
+identify	O
+the	O
+principal	O
+dimensions	O
+of	O
+the	O
+Framingham	O
+Type	O
+A	O
+scale	O
+(	O
+FTAS	O
+)	O
+and	O
+then	O
+to	O
+examine	O
+their	O
+physiological	O
+and	O
+psychological	O
+correlates	O
+.	O
+
+A	O
+preliminary	O
+study	O
+on	O
+pyogenic	O
+arthritis	O
+.	O
+
+Legionella	O
+,	O
+microbial	O
+ecology	O
+,	O
+and	O
+inconspicuous	O
+consumption	O
+.	O
+
+Lymphatics	O
+in	O
+the	O
+aorta	O
+of	O
+rats	O
+treated	O
+with	O
+a	O
+soy	O
+-	O
+bean	O
+oil	O
+extract	O
+(	O
+lipofundin	O
+)	O
+.	O
+
+For	O
+signal	O
+durations	O
+less	O
+than	O
+10	O
+ms	O
+,	O
+however	O
+,	O
+the	O
+SoNo	O
+and	O
+S	O
+pi	O
+No	O
+threshold	O
+functions	O
+converged	O
+and	O
+the	O
+masking	O
+-	O
+level	O
+difference	O
+decreased	O
+.	O
+
+The	O
+spleen	O
+rate	O
+of	O
+about	O
+600	O
+villagers	O
+of	O
+RK	O
+I	O
+examined	O
+was	O
+54	O
+.	O
+3	O
+%	O
+and	O
+the	O
+parasite	O
+rate	O
+13	O
+.	O
+2	O
+%	O
+before	O
+the	O
+drug	O
+intervention	O
+.	O
+
+Multiple	O
+dosing	O
+four	O
+times	O
+daily	O
+for	O
+7	O
+days	O
+of	O
+indoprofen	O
+200	O
+mg	O
+,	O
+a	O
+non	O
+-	O
+steroidal	O
+anti	O
+-	O
+inflammatory	O
+drug	O
+with	O
+a	O
+short	O
+half	O
+-	O
+life	O
+(	O
+t1	O
+/	O
+2	O
+)	O
+,	O
+revealed	O
+drug	O
+accumulation	O
+in	O
+eight	O
+elderly	O
+subjects	O
+.	O
+
+In	O
+10	O
+patients	O
+with	O
+subacute	O
+cardiac	O
+tamponade	O
+,	O
+pulmonary	O
+wedge	O
+pressure	O
+(	O
+PWP	O
+)	O
+,	O
+RAP	O
+,	O
+and	O
+IPP	O
+were	O
+measured	O
+along	O
+with	O
+indexes	O
+of	O
+systolic	O
+function	O
+.	O
+
+Encompassing	O
+tamponade	O
+and	O
+pericardiocentesis	O
+data	O
+,	O
+left	O
+ventricular	O
+stroke	O
+work	O
+index	O
+showed	O
+positive	O
+correlation	O
+with	O
+TMFP1	O
+(	O
+r	O
+=	O
+.	O
+59	O
+)	O
+and	O
+TMFP2	O
+(	O
+r	O
+=	O
+.	O
+52	O
+)	O
+but	O
+not	O
+with	O
+TMFP3	O
+.	O
+
+Rabbits	O
+developed	O
+profound	O
+hypocalcemia	O
+,	O
+with	O
+levels	O
+falling	O
+from	O
+15	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+2	O
+to	O
+7	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+4	O
+mg	O
+/	O
+dl	O
+under	O
+the	O
+influence	O
+of	O
+TSST	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Similarly	O
+,	O
+actuarial	O
+interpretations	O
+for	O
+the	O
+second	O
+protocols	O
+were	O
+not	O
+more	O
+frequently	O
+selected	O
+by	O
+therapists	O
+as	O
+more	O
+valid	O
+,	O
+regardless	O
+of	O
+treatment	O
+condition	O
+and	O
+elevation	O
+of	O
+the	O
+F	O
+and	O
+F	O
+-	O
+K	O
+indices	O
+on	O
+the	O
+first	O
+MMPI	O
+profile	O
+.	O
+
+The	O
+study	O
+disclosed	O
+generalized	O
+atrophy	O
+and	O
+diffuse	O
+symmetric	O
+white	O
+matter	O
+hypodensities	O
+.	O
+
+The	O
+diagnosis	O
+of	O
+metachromatic	O
+leukodystrophy	O
+(	O
+MLD	O
+)	O
+was	O
+confirmed	O
+by	O
+the	O
+finding	O
+of	O
+low	O
+arylsulfatase	B-GENE
+A	I-GENE
+(	O
+ASA	B-GENE
+)	O
+levels	O
+in	O
+cultured	O
+fibroblasts	O
+in	O
+both	O
+sisters	O
+.	O
+
+Drugs	O
+that	O
+are	O
+transformed	O
+via	O
+phase	O
+II	O
+reactions	O
+usually	O
+do	O
+not	O
+require	O
+dosage	O
+adjustment	O
+.	O
+
+A	O
+study	O
+of	O
+human	O
+genes	O
+coding	O
+for	O
+U4	B-GENE
+small	I-GENE
+nuclear	I-GENE
+RNA	I-GENE
+is	O
+presented	O
+.	O
+
+Using	O
+the	O
+balloon	O
+-	O
+gas	O
+procedure	O
+with	O
+a	O
+single	O
+gas	O
+injection	O
+,	O
+a	O
+bubble	O
+was	O
+obtained	O
+that	O
+was	O
+large	O
+enough	O
+to	O
+tamponade	O
+a	O
+giant	O
+tear	O
+without	O
+prior	O
+drainage	O
+of	O
+subretinal	O
+fluid	O
+or	O
+vitrectomy	O
+.	O
+
+Development	O
+of	O
+a	O
+provisional	O
+information	O
+-	O
+retrieval	O
+descriptor	O
+language	O
+for	O
+"	O
+Roentgenology	O
+and	O
+Medical	O
+Radiology	O
+"	O
+for	O
+use	O
+in	O
+the	O
+Medinform	O
+system	O
+
+Persistent	O
+acantholytic	O
+dermatosis	O
+with	O
+increased	O
+light	O
+sensitivity	O
+
+Thus	O
+,	O
+a	O
+negative	O
+test	O
+is	O
+compatible	O
+with	O
+low	O
+disease	O
+activity	O
+and	O
+/	O
+or	O
+efficacy	O
+of	O
+calcium	O
+antagonist	O
+treatment	O
+.	O
+
+Thus	O
+,	O
+a	O
+negative	O
+test	O
+is	O
+compatible	O
+with	O
+low	O
+disease	O
+activity	O
+and	O
+/	O
+or	O
+efficacy	O
+of	O
+calcium	O
+antagonist	O
+treatment	O
+.	O
+
+Dorsal	O
+foot	O
+TcpO2	O
+was	O
+measured	O
+by	O
+using	O
+oxygen	O
+-	O
+sensing	O
+electrodes	O
+with	O
+surface	O
+temperatures	O
+of	O
+42	O
+degrees	O
+C	O
+and	O
+45	O
+degrees	O
+C	O
+;	O
+in	O
+theory	O
+,	O
+changes	O
+in	O
+sympathetic	O
+activity	O
+should	O
+affect	O
+vasomotor	O
+tone	O
+and	O
+TcpO2	O
+in	O
+skin	O
+beneath	O
+an	O
+electrode	O
+at	O
+42	O
+degrees	O
+C	O
+(	O
+submaximal	O
+vasodilation	O
+)	O
+,	O
+but	O
+not	O
+at	O
+45	O
+degrees	O
+C	O
+(	O
+maximal	O
+vasodilation	O
+)	O
+.	O
+
+In	O
+subjects	O
+(	O
+n	O
+=	O
+5	O
+)	O
+with	O
+quadriplegia	O
+and	O
+reduced	O
+sympathetic	O
+tone	O
+secondary	O
+to	O
+cervical	O
+cord	O
+trauma	O
+,	O
+TcpO2	O
+at	O
+42	O
+degrees	O
+C	O
+and	O
+vasodilation	O
+index	O
+were	O
+increased	O
+(	O
+45	O
+.	O
+0	O
+mmHg	O
+and	O
+0	O
+.	O
+61	O
+)	O
+;	O
+TcpO2	O
+at	O
+45	O
+degrees	O
+C	O
+did	O
+not	O
+change	O
+.	O
+
+The	O
+other	O
+model	O
+was	O
+a	O
+continuous	O
+exponential	O
+plus	O
+constant	O
+of	O
+the	O
+form	O
+La	O
+-	O
+=	O
+a	O
++	O
+b	O
+[	O
+exp	O
+(	O
+cVO2	O
+)	O
+]	O
+.	O
+
+Cell	O
+.	O
+
+Timing	O
+of	O
+symptoms	O
+and	O
+oocyst	O
+excretion	O
+in	O
+human	O
+cryptosporidiosis	O
+.	O
+
+After	O
+dopamine	O
+infusion	O
+in	O
+women	O
+with	O
+polycystic	O
+ovary	O
+syndrome	O
+and	O
+in	O
+matched	O
+controls	O
+,	O
+steady	O
+state	O
+levels	O
+of	O
+plasma	O
+dopamine	O
+,	O
+norepinephrine	O
+,	O
+and	O
+the	O
+ratio	O
+of	O
+dopamine	O
+/	O
+norepinephrine	O
+were	O
+similar	O
+in	O
+the	O
+two	O
+groups	O
+.	O
+
+Diagnostic	O
+importance	O
+of	O
+determining	O
+the	O
+complement	O
+constituents	O
+in	O
+children	O
+with	O
+autoimmune	O
+thyroiditis	O
+
+The	O
+4	O
+patients	O
+with	O
+carboxyhemoglobin	B-GENE
+levels	O
+in	O
+excess	O
+of	O
+10	O
+%	O
+may	O
+represent	O
+occult	O
+carbon	O
+monoxide	O
+poisoning	O
+in	O
+this	O
+population	O
+.	O
+
+All	O
+these	O
+processes	O
+were	O
+fully	O
+developed	O
+during	O
+the	O
+last	O
+month	O
+of	O
+pregnancy	O
+,	O
+offering	O
+the	O
+same	O
+picture	O
+as	O
+the	O
+controls	O
+.	O
+
+Hypoglycemic	O
+action	O
+of	O
+"	O
+he	O
+xiang	O
+zhuang	O
+qi	O
+gong	O
+"	O
+and	O
+its	O
+mechanism	O
+on	O
+diabetes	O
+mellitus	O
+
+This	O
+region	O
+of	O
+60	O
+amino	O
+acids	O
+may	O
+be	O
+involved	O
+in	O
+coiled	O
+-	O
+coil	O
+interactions	O
+similar	O
+to	O
+those	O
+that	O
+facilitate	O
+the	O
+filament	O
+formation	O
+in	O
+the	O
+rod	O
+region	O
+.	O
+
+This	O
+approach	O
+enables	O
+the	O
+sources	O
+of	O
+error	O
+in	O
+the	O
+calculation	O
+of	O
+nutrient	O
+utilization	O
+to	O
+be	O
+readily	O
+identified	O
+,	O
+and	O
+their	O
+effect	O
+on	O
+precision	O
+to	O
+be	O
+assessed	O
+in	O
+different	O
+nutritional	O
+and	O
+metabolic	O
+states	O
+.	O
+
+The	O
+effect	O
+of	O
+dietary	O
+zinc	O
+deficiency	O
+on	O
+the	O
+mossy	O
+fiber	O
+zinc	O
+content	O
+of	O
+the	O
+rat	O
+hippocampus	O
+.	O
+
+Weaned	O
+rats	O
+were	O
+fed	O
+a	O
+normal	O
+diet	O
+or	O
+a	O
+low	O
+-	O
+protein	O
+,	O
+low	O
+-	O
+energy	O
+diet	O
+,	O
+and	O
+injected	O
+with	O
+saline	O
+or	O
+thyroxine	O
+(	O
+5	O
+micrograms	O
+/	O
+100	O
+g	O
+BW	O
+)	O
+for	O
+22	O
+days	O
+.	O
+
+The	O
+effects	O
+of	O
+several	O
+opioid	O
+agonists	O
+and	O
+the	O
+opioid	O
+antagonist	O
+naloxone	O
+were	O
+examined	O
+in	O
+rats	O
+responding	O
+under	O
+a	O
+fixed	O
+-	O
+consecutive	O
+-	O
+number	O
+(	O
+FCN	O
+)	O
+schedule	O
+.	O
+
+The	O
+rate	O
+-	O
+decreasing	O
+effects	O
+of	O
+morphine	O
+and	O
+U50488	O
+were	O
+reversed	O
+completely	O
+by	O
+a	O
+0	O
+.	O
+01	O
+and	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+dose	O
+of	O
+naloxone	O
+,	O
+respectively	O
+.	O
+
+An	O
+intralobar	O
+change	O
+in	O
+temperature	O
+above	O
+or	O
+below	O
+36	O
+degrees	O
+C	O
+decreases	O
+only	O
+the	O
+lobar	O
+bronchial	O
+blood	O
+flow	O
+and	O
+does	O
+not	O
+influence	O
+blood	O
+flow	O
+to	O
+other	O
+nearby	O
+tissues	O
+including	O
+those	O
+vascularized	O
+by	O
+the	O
+bronchial	O
+circulation	O
+.	O
+
+Convulsive	O
+status	O
+epilepticus	O
+after	O
+infusion	O
+of	O
+cisplatin	O
+
+The	O
+following	O
+markers	O
+were	O
+looked	O
+for	O
+in	O
+the	O
+serum	O
+,	O
+skin	O
+and	O
+liver	O
+of	O
+all	O
+patients	O
+with	O
+chronic	O
+hepatitis	O
+:	O
+HBV	O
+(	O
+HBs	B-GENE
+Ag	I-GENE
+and	O
+HBe	B-GENE
+Ag	I-GENE
+,	O
+anti	B-GENE
+-	I-GENE
+HBs	I-GENE
+,	O
+anti	B-GENE
+-	I-GENE
+HBe	I-GENE
+and	O
+anti	B-GENE
+-	I-GENE
+HBc	I-GENE
+in	O
+the	O
+serum	O
+,	O
+HBs	B-GENE
+and	I-GENE
+HBc	I-GENE
+Ag	I-GENE
+in	O
+the	O
+liver	O
+)	O
+;	O
+non	B-GENE
+-	I-GENE
+A	I-GENE
+non	I-GENE
+-	I-GENE
+B	I-GENE
+(	O
+non	B-GENE
+-	I-GENE
+A	I-GENE
+,	I-GENE
+non	I-GENE
+-	I-GENE
+B	I-GENE
+Ag	I-GENE
+and	I-GENE
+antibody	I-GENE
+,	O
+anti	B-GENE
+non	I-GENE
+-	I-GENE
+A	I-GENE
+non	I-GENE
+-	I-GENE
+Bc	I-GENE
+in	O
+the	O
+serum	O
+,	O
+non	B-GENE
+-	I-GENE
+A	I-GENE
+,	I-GENE
+non	I-GENE
+-	I-GENE
+Bc	I-GENE
+Ag	I-GENE
+in	O
+the	O
+liver	O
+)	O
+.	O
+
+Groups	O
+of	O
+male	O
+and	O
+female	O
+Fischer	O
+344	O
+rats	O
+,	O
+B6C3F1	O
+mice	O
+,	O
+and	O
+Hartley	O
+guinea	O
+pigs	O
+were	O
+exposed	O
+once	O
+for	O
+6	O
+hr	O
+to	O
+mean	O
+concentrations	O
+of	O
+10	O
+.	O
+5	O
+,	O
+5	O
+.	O
+4	O
+,	O
+2	O
+.	O
+4	O
+,	O
+1	O
+.	O
+0	O
+,	O
+or	O
+0	O
+(	O
+control	O
+)	O
+ppm	O
+of	O
+methyl	O
+isocyanate	O
+(	O
+MIC	O
+)	O
+vapor	O
+.	O
+
+Radionuclide	O
+study	O
+and	O
+endomyocardial	O
+biopsy	O
+revealed	O
+remarkable	O
+degeneration	O
+of	O
+myocardium	O
+.	O
+
+Immobilization	O
+of	O
+the	O
+fracture	O
+in	O
+a	O
+collar	O
+and	O
+cuff	O
+sling	O
+was	O
+as	O
+effective	O
+as	O
+more	O
+elaborate	O
+methods	O
+.	O
+
+Comparison	O
+of	O
+patients	O
+receiving	O
+phenytoin	O
+and	O
+those	O
+who	O
+were	O
+not	O
+showed	O
+significantly	O
+lower	O
+serum	O
+folate	O
+in	O
+the	O
+sub	O
+-	O
+group	O
+receiving	O
+phenytoin	O
+,	O
+but	O
+there	O
+was	O
+no	O
+significant	O
+difference	O
+between	O
+the	O
+sub	O
+-	O
+groups	O
+with	O
+respect	O
+to	O
+vitamin	O
+B12	O
+or	O
+behaviour	O
+problem	O
+rating	O
+.	O
+
+Typical	O
+and	O
+atypical	O
+clinical	O
+features	O
+of	O
+this	O
+lacrimal	O
+sac	O
+cyst	O
+are	O
+emphasized	O
+.	O
+
+The	O
+role	O
+of	O
+saliva	O
+in	O
+sour	O
+taste	O
+perception	O
+was	O
+investigated	O
+in	O
+a	O
+series	O
+of	O
+4	O
+experiments	O
+.	O
+
+Separate	O
+experiments	O
+measured	O
+AIB	O
+and	O
+86RbCl	O
+uptake	O
+in	O
+36B	O
+-	O
+10	O
+cells	O
+in	O
+vitro	O
+1	O
+and	O
+2	O
+days	O
+following	O
+20	O
+Gy	O
+irradiation	O
+to	O
+assess	O
+whether	O
+this	O
+radiation	O
+dose	O
+reduced	O
+the	O
+capacity	O
+of	O
+tumor	O
+cells	O
+to	O
+trap	O
+AIB	O
+or	O
+Rb	O
++	O
+.	O
+
+For	O
+patients	O
+with	O
+recurrent	O
+or	O
+metastatic	O
+disease	O
+,	O
+the	O
+data	O
+suggest	O
+that	O
+I	O
+-	O
+131	O
+MIBG	O
+scintigraphy	O
+is	O
+the	O
+examination	O
+of	O
+choice	O
+.	O
+
+W	O
+.	O
+
+Cyclosporine	O
+treatment	O
+for	O
+intractable	O
+polymyositis	O
+.	O
+
+In	O
+addition	O
+,	O
+on	O
+the	O
+Cohler	O
+'	O
+s	O
+maternal	O
+scale	O
+,	O
+Korean	O
+mothers	O
+were	O
+found	O
+to	O
+view	O
+their	O
+infants	O
+as	O
+more	O
+passive	O
+and	O
+dependent	O
+than	O
+American	O
+mothers	O
+did	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+00	O
+)	O
+.	O
+
+A	O
+preoperative	O
+teaching	O
+booklet	O
+for	O
+pediatric	O
+patients	O
+.	O
+
+Hyperthyroidism	O
+
+We	O
+conclude	O
+that	O
+for	O
+mono	O
+-	O
+intronic	O
+precursors	O
+in	O
+which	O
+there	O
+is	O
+only	O
+one	O
+choice	O
+of	O
+splice	O
+sites	O
+,	O
+most	O
+of	O
+the	O
+exon	O
+sequences	O
+are	O
+not	O
+mechanistically	O
+involved	O
+in	O
+the	O
+splicing	O
+process	O
+.	O
+
+UVA	O
+-	O
+induced	O
+melanocytic	O
+lesions	O
+.	O
+
+Ex	O
+vivo	O
+MAO	B-GENE
+inhibition	O
+data	O
+indicated	O
+DPGPEA	O
+to	O
+be	O
+an	O
+inhibitor	O
+of	O
+MAO	B-GENE
+-	I-GENE
+B	I-GENE
+,	O
+although	O
+the	O
+effect	O
+was	O
+much	O
+weaker	O
+than	O
+seen	O
+with	O
+tranylcypromine	O
+or	O
+pargyline	O
+.	O
+
+Thus	O
+in	O
+this	O
+region	O
+of	O
+the	O
+vessel	O
+pyridinoline	O
+represents	O
+the	O
+major	O
+stabilising	O
+crosslink	O
+of	O
+collagen	B-GENE
+.	O
+
+A	O
+careful	O
+,	O
+radiolabelled	O
+tissue	O
+-	O
+distribution	O
+study	O
+is	O
+warranted	O
+to	O
+elucidate	O
+the	O
+complicated	O
+metabolic	O
+fate	O
+of	O
+perhexiline	O
+.	O
+
+Systemic	O
+lupus	O
+erythematosus	O
+was	O
+diagnosed	O
+.	O
+
+In	O
+the	O
+evening	O
+,	O
+the	O
+amplitude	O
+of	O
+the	O
+responses	O
+to	O
+both	O
+O2	O
+and	O
+CO2	O
+increased	O
+but	O
+the	O
+increase	O
+in	O
+CO2	O
+sensitivity	O
+was	O
+proportionally	O
+more	O
+important	O
+.	O
+
+The	O
+statistical	O
+significance	O
+of	O
+the	O
+prognosis	O
+factors	O
+was	O
+studied	O
+by	O
+uni	O
+-	O
+and	O
+multivariative	O
+methods	O
+,	O
+according	O
+to	O
+the	O
+model	O
+of	O
+Cox	O
+,	O
+with	O
+the	O
+help	O
+of	O
+an	O
+IMB	O
+computer	O
+.	O
+
+These	O
+changes	O
+at	O
+the	O
+site	O
+of	O
+injection	O
+consist	O
+of	O
+a	O
+focal	O
+abnormality	O
+characterized	O
+by	O
+a	O
+slight	O
+increase	O
+in	O
+signal	O
+intensity	O
+on	O
+T1	O
+weighted	O
+images	O
+and	O
+markedly	O
+increased	O
+signal	O
+intensity	O
+on	O
+T2	O
+weighted	O
+images	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+less	O
+antidopaminergic	O
+activity	O
+of	O
+RHAL	O
+in	O
+this	O
+neuroleptic	O
+test	O
+might	O
+be	O
+explained	O
+by	O
+the	O
+lesser	O
+conversion	O
+of	O
+RHAL	O
+to	O
+HAL	O
+.	O
+
+Organisms	O
+were	O
+recovered	O
+from	O
+the	O
+conjunctiva	O
+for	O
+several	O
+weeks	O
+,	O
+and	O
+persistent	O
+genital	O
+and	O
+gastrointestinal	O
+infection	O
+also	O
+resulted	O
+from	O
+the	O
+ocular	O
+infection	O
+in	O
+some	O
+cats	O
+.	O
+
+In	O
+vivo	O
+epiluminescence	O
+microscopy	O
+of	O
+pigmented	O
+skin	O
+lesions	O
+.	O
+
+These	O
+equilibrium	O
+solutions	O
+are	O
+then	O
+shown	O
+to	O
+arise	O
+from	O
+the	O
+vertices	O
+of	O
+a	O
+particular	O
+convex	O
+polyhedron	O
+.	O
+
+Statistically	O
+significant	O
+effects	O
+were	O
+noted	O
+at	O
+doses	O
+which	O
+did	O
+not	O
+appear	O
+to	O
+be	O
+maternally	O
+toxic	O
+.	O
+
+Low	O
+MAO	B-GENE
+subjects	O
+showed	O
+a	O
+pattern	O
+of	O
+higher	O
+scores	O
+in	O
+KSP	O
+Impulsiveness	O
+,	O
+EPQ	O
+Neuroticism	O
+,	O
+and	O
+KSP	O
+Somatic	O
+Anxiety	O
+and	O
+Irritability	O
+and	O
+lower	O
+scores	O
+in	O
+KSP	O
+Socialization	O
+,	O
+in	O
+line	O
+with	O
+personality	O
+profiles	O
+found	O
+in	O
+alcoholics	O
+,	O
+psychopaths	O
+,	O
+and	O
+suicide	O
+attempters	O
+who	O
+also	O
+tend	O
+to	O
+have	O
+low	O
+platelet	O
+MAO	B-GENE
+activity	O
+.	O
+
+In	O
+group	O
+I	O
+,	O
+Paw	O
+,	O
+delta	O
+V	O
+,	O
+PaO2	O
+,	O
+Vinj	O
+and	O
+VT	O
+significantly	O
+decreased	O
+whereas	O
+operating	O
+pressure	O
+and	O
+E	O
+significantly	O
+increased	O
+when	O
+the	O
+internal	O
+diameter	O
+of	O
+the	O
+injector	O
+cannula	O
+was	O
+reduced	O
+.	O
+
+In	O
+calves	O
+receiving	O
+milk	O
+-	O
+substitute	O
+diets	O
+containing	O
+80	O
+-	O
+260	O
+g	O
+DM	O
+/	O
+kg	O
+,	O
+milk	O
+intakes	O
+were	O
+reduced	O
+by	O
+up	O
+to	O
+30	O
+%	O
+on	O
+the	O
+1st	O
+day	O
+that	O
+calves	O
+were	O
+fed	O
+once	O
+daily	O
+instead	O
+of	O
+twice	O
+daily	O
+.	O
+
+Today	O
+there	O
+is	O
+no	O
+doubt	O
+that	O
+elevated	O
+plasma	O
+cholesterol	O
+levels	O
+should	O
+be	O
+lowered	O
+first	O
+by	O
+dietary	O
+modification	O
+even	O
+in	O
+early	O
+childhood	O
+,	O
+beginning	O
+at	O
+the	O
+age	O
+of	O
+two	O
+years	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+N	O
+-	O
+nitroso	O
+compounds	O
+can	O
+be	O
+formed	O
+in	O
+vivo	O
+in	O
+the	O
+infected	O
+bladder	O
+,	O
+which	O
+could	O
+explain	O
+the	O
+association	O
+between	O
+urinary	O
+-	O
+tract	O
+infections	O
+and	O
+increased	O
+risk	O
+for	O
+bladder	O
+cancer	O
+.	O
+
+Epithelial	O
+nerve	O
+fiber	O
+defects	O
+included	O
+absence	O
+or	O
+distorted	O
+architecture	O
+of	O
+the	O
+basal	O
+epithelial	O
+plexus	O
+and	O
+intra	O
+-	O
+epithelial	O
+terminals	O
+.	O
+
+The	O
+histologic	O
+grade	O
+for	O
+the	O
+same	O
+anatomic	O
+site	O
+varied	O
+among	O
+hearts	O
+and	O
+among	O
+different	O
+anatomic	O
+sites	O
+in	O
+the	O
+same	O
+heart	O
+.	O
+
+Serum	O
+levels	O
+of	O
+albumin	B-GENE
+,	O
+globulin	B-GENE
+,	O
+and	O
+coagulation	B-GENE
+protein	I-GENE
+activity	O
+were	O
+measured	O
+preshock	O
+,	O
+postshock	O
+,	O
+and	O
+daily	O
+for	O
+3	O
+days	O
+;	O
+skin	O
+lymph	O
+levels	O
+were	O
+measured	O
+on	O
+Day	O
+3	O
+.	O
+
+For	O
+colostral	O
+milk	O
+there	O
+was	O
+a	O
+significant	O
+correlation	O
+of	O
+vitamin	O
+K1	O
+to	O
+cholesterol	O
+(	O
+r	O
+=	O
+0	O
+.	O
+62	O
+)	O
+but	O
+not	O
+to	O
+total	O
+lipid	O
+or	O
+phospholipid	O
+suggesting	O
+a	O
+role	O
+for	O
+cholesterol	O
+in	O
+the	O
+secretion	O
+of	O
+vitamin	O
+K1	O
+into	O
+colostral	O
+milk	O
+.	O
+
+Endurance	O
+training	O
+resulted	O
+in	O
+an	O
+increase	O
+of	O
+stiffness	O
+associated	O
+with	O
+a	O
+decrease	O
+of	O
+type	O
+II	O
+fibers	O
+.	O
+
+A	O
+rate	O
+-	O
+decreasing	O
+dose	O
+of	O
+physostigmine	O
+,	O
+an	O
+acetylcholinesterase	B-GENE
+inhibitor	O
+,	O
+was	O
+studied	O
+in	O
+combination	O
+with	O
+the	O
+range	O
+of	O
+atropine	O
+doses	O
+.	O
+
+References	O
+for	O
+occupational	O
+fitness	O
+of	O
+adolescents	O
+with	O
+diseases	O
+of	O
+the	O
+respiratory	O
+tract	O
+and	O
+lungs	O
+
+Salzburg	O
+,	O
+9	O
+-	O
+12	O
+September	O
+1987	O
+.	O
+
+Two	O
+new	O
+glucosidase	B-GENE
+inhibitors	O
+(	O
+BAY	O
+m	O
+1099	O
+and	O
+BAY	O
+o	O
+1248	O
+)	O
+were	O
+studied	O
+in	O
+volunteers	O
+and	O
+type	O
+II	O
+diabetics	O
+under	O
+various	O
+conditions	O
+.	O
+
+The	O
+models	O
+accurately	O
+localized	O
+the	O
+common	O
+boundaries	O
+between	O
+the	O
+PBB	O
+and	O
+CN	O
+.	O
+
+However	O
+,	O
+conversions	O
+of	O
+12	O
+mm	O
+or	O
+more	O
+from	O
+a	O
+documented	O
+negative	O
+result	O
+indicated	O
+spread	O
+of	O
+infection	O
+.	O
+
+The	O
+maximum	O
+amplitude	O
+of	O
+evoked	O
+responses	O
+in	O
+the	O
+cervical	O
+sympathetic	O
+trunk	O
+was	O
+obtained	O
+when	O
+the	O
+T2	O
+white	O
+ramus	O
+was	O
+stimulated	O
+and	O
+decreased	O
+gradually	O
+when	O
+followed	O
+by	O
+the	O
+stimulation	O
+of	O
+T1	O
+,	O
+T3	O
+,	O
+T4	O
+and	O
+T5	O
+white	O
+rami	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+contact	O
+allergy	O
+to	O
+K	O
+-	O
+CG	O
+is	O
+common	O
+.	O
+
+The	O
+effect	O
+of	O
+a	O
+beta	B-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+antagonist	O
+,	O
+pindolol	O
+,	O
+on	O
+uterine	O
+smooth	O
+muscle	O
+in	O
+term	O
+pregnant	O
+women	O
+was	O
+studied	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+(	O
+in	O
+hypertensive	O
+women	O
+)	O
+.	O
+
+The	O
+less	O
+-	O
+polar	O
+mycolic	O
+acid	O
+-	O
+containing	O
+Rhodococcus	O
+species	O
+showed	O
+chromatographic	O
+patterns	O
+that	O
+partially	O
+overlapped	O
+(	O
+in	O
+elution	O
+times	O
+)	O
+the	O
+patterns	O
+of	O
+Nocardia	O
+asteroides	O
+,	O
+N	O
+.	O
+otitidiscaviarum	O
+,	O
+and	O
+N	O
+.	O
+brasiliensis	O
+,	O
+but	O
+the	O
+larger	O
+number	O
+of	O
+peaks	O
+in	O
+the	O
+last	O
+species	O
+made	O
+separation	O
+between	O
+the	O
+genera	O
+possible	O
+.	O
+
+Blood	B-GENE
+serum	I-GENE
+erythropoietin	I-GENE
+level	O
+and	O
+basic	O
+hematological	O
+indices	O
+during	O
+the	O
+adaptation	O
+of	O
+healthy	O
+newborn	O
+infants	O
+
+49	O
+,	O
+XXXXY	O
+chromosome	O
+anomaly	O
+:	O
+an	O
+unusual	O
+variant	O
+of	O
+Klinefelter	O
+'	O
+s	O
+syndrome	O
+.	O
+
+Oxygen	O
+delivery	O
+and	O
+consumption	O
+and	O
+P50	O
+in	O
+patients	O
+with	O
+acute	O
+myocardial	O
+infarction	O
+.	O
+
+Infants	O
+of	O
+this	O
+sample	O
+had	O
+monocular	O
+PL	O
+visual	O
+acuities	O
+similar	O
+to	O
+those	O
+established	O
+by	O
+McDonald	O
+et	O
+al	O
+.	O
+in	O
+a	O
+laboratory	O
+setting	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+the	O
+effect	O
+of	O
+the	O
+isomers	O
+of	O
+pentobarbital	O
+and	O
+secobarbital	O
+on	O
+mult	O
+FR30	O
+FI600	O
+responding	O
+and	O
+on	O
+suppressed	O
+responding	O
+are	O
+qualitatively	O
+similar	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+The	O
+number	O
+of	O
+crystalline	O
+deposits	O
+is	O
+less	O
+in	O
+the	O
+advanced	O
+atrophic	O
+areas	O
+of	O
+the	O
+RPE	O
+-	O
+choriocapillaris	O
+complex	O
+.	O
+
+All	O
+33	O
+subjects	O
+were	O
+given	O
+psychometric	O
+instruments	O
+for	O
+measuring	O
+various	O
+components	O
+of	O
+anger	O
+and	O
+anxiety	O
+:	O
+Spielberger	O
+'	O
+s	O
+State	O
+-	O
+Trait	O
+Personality	O
+Inventory	O
+,	O
+the	O
+Anger	O
+Expression	O
+Scale	O
+,	O
+and	O
+the	O
+State	O
+Anger	O
+Reaction	O
+Scale	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+the	O
+primary	O
+visual	O
+cortex	O
+of	O
+the	O
+rat	O
+is	O
+asymmetrical	O
+in	O
+volume	O
+,	O
+and	O
+that	O
+the	O
+asymmetry	O
+reflects	O
+side	O
+differences	O
+in	O
+the	O
+number	O
+of	O
+neurons	O
+.	O
+
+The	O
+subjects	O
+received	O
+a	O
+single	O
+500	O
+mg	O
+dose	O
+of	O
+acetaminophen	O
+i	O
+.	O
+v	O
+.	O
+and	O
+concentrations	O
+in	O
+plasma	O
+were	O
+measured	O
+for	O
+360	O
+minutes	O
+and	O
+in	O
+urine	O
+for	O
+24	O
+h	O
+in	O
+order	O
+to	O
+estimate	O
+the	O
+production	O
+of	O
+metabolites	O
+.	O
+
+Mean	O
+weighted	O
+skin	O
+temperature	O
+(	O
+Tsk	O
+)	O
+was	O
+lower	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+following	O
+acclimation	O
+than	O
+before	O
+,	O
+and	O
+acclimation	O
+resulted	O
+in	O
+a	O
+larger	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+02	O
+)	O
+Tre	O
+-	O
+to	O
+-	O
+Tsk	O
+gradient	O
+.	O
+
+Indium	O
+-	O
+111	O
+leukocyte	O
+imaging	O
+in	O
+patients	O
+with	O
+rheumatoid	O
+arthritis	O
+.	O
+
+The	O
+effect	O
+of	O
+L	O
+-	O
+methionine	O
+supplementation	O
+on	O
+the	O
+utilization	O
+of	O
+a	O
+soy	O
+protein	O
+isolate	O
+(	O
+SPI	O
+)	O
+was	O
+evaluated	O
+by	O
+short	O
+-	O
+term	O
+nitrogen	O
+balance	O
+studies	O
+in	O
+young	O
+women	O
+.	O
+
+Primary	O
+invasive	O
+Haemophilus	O
+influenzae	O
+type	O
+b	O
+disease	O
+:	O
+a	O
+population	O
+-	O
+based	O
+assessment	O
+of	O
+risk	O
+factors	O
+.	O
+
+Overall	O
+,	O
+lesions	O
+infiltrating	O
+the	O
+deep	O
+lamina	O
+propria	O
+do	O
+not	O
+exhibit	O
+a	O
+reduced	O
+frequency	O
+of	O
+occurrence	O
+compared	O
+to	O
+lesions	O
+infiltrating	O
+the	O
+skeletal	O
+muscle	O
+;	O
+however	O
+,	O
+carcinomas	O
+affecting	O
+other	O
+oral	O
+sites	O
+showed	O
+a	O
+reduced	O
+frequency	O
+of	O
+deeply	O
+infiltrating	O
+lesions	O
+in	O
+comparison	O
+to	O
+more	O
+superficial	O
+lesions	O
+.	O
+
+Factors	O
+that	O
+showed	O
+significant	O
+correlation	O
+to	O
+elevated	O
+CIC	O
+'	O
+s	O
+in	O
+the	O
+highly	O
+elevated	O
+portion	O
+of	O
+our	O
+CIC	O
+population	O
+were	O
+poor	O
+NIH	O
+score	O
+,	O
+increased	O
+patient	O
+age	O
+,	O
+low	O
+peak	O
+expiratory	O
+flow	O
+rate	O
+,	O
+and	O
+elevated	O
+total	O
+serum	B-GENE
+IgG	I-GENE
+.	O
+
+Induction	O
+of	O
+both	O
+potential	O
+transcripts	O
+follows	O
+heat	O
+shock	O
+in	O
+vivo	O
+.	O
+
+New	O
+and	O
+successful	O
+steps	O
+have	O
+been	O
+made	O
+in	O
+immunodiagnostics	O
+,	O
+immunotherapy	O
+,	O
+and	O
+immunoprophylaxis	O
+of	O
+immunologically	O
+conditioned	O
+infertility	O
+.	O
+
+Estimated	O
+nucleic	O
+acid	O
+N	O
+absorption	O
+is	O
+7	O
+-	O
+8	O
+%	O
+of	O
+N	O
+intake	O
+.	O
+
+Adhesion	O
+,	O
+phagocytosis	O
+,	O
+chemotactic	O
+and	O
+random	O
+migration	O
+,	O
+nitroblue	O
+tetrazolium	O
+dye	O
+reduction	O
+of	O
+peritoneal	O
+exudate	O
+neutrophils	O
+and	O
+macrophages	O
+,	O
+fibrinogen	B-GENE
+level	O
+,	O
+gelation	O
+of	O
+soluble	O
+fibrin	B-GENE
+and	O
+serial	O
+dilution	O
+protamine	O
+sulfate	O
+test	O
+were	O
+investigated	O
+in	O
+115	O
+New	O
+Zealand	O
+white	O
+rabbits	O
+with	O
+experimentally	O
+induced	O
+Shwartzman	O
+phenomenon	O
+in	O
+the	O
+colon	O
+,	O
+and	O
+in	O
+control	O
+animals	O
+.	O
+
+The	O
+FFA	O
+levels	O
+were	O
+not	O
+affected	O
+(	O
+P	O
+greater	O
+than	O
+.	O
+1	O
+)	O
+by	O
+meal	O
+interval	O
+.	O
+
+He	O
+visited	O
+our	O
+hospital	O
+and	O
+left	O
+solitary	O
+renal	O
+cyst	O
+was	O
+suspected	O
+.	O
+
+However	O
+,	O
+further	O
+analyses	O
+of	O
+the	O
+data	O
+indicate	O
+that	O
+increasing	O
+VO2	O
+AT	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+63	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+rather	O
+than	O
+VO2max	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+15	O
+)	O
+could	O
+result	O
+in	O
+improving	O
+the	O
+10	O
+,	O
+000	O
+m	O
+race	O
+performance	O
+to	O
+a	O
+larger	O
+extent	O
+,	O
+and	O
+that	O
+the	O
+absolute	O
+amount	O
+of	O
+change	O
+(	O
+delta	O
+)	O
+in	O
+the	O
+10	O
+,	O
+000	O
+m	O
+run	O
+time	O
+is	O
+best	O
+accounted	O
+for	O
+by	O
+a	O
+combination	O
+of	O
+delta	O
+VO2	O
+AT	O
+and	O
+delta	O
+5	O
+,	O
+000	O
+m	O
+run	O
+time	O
+.	O
+
+A	O
+significant	O
+herd	O
+X	O
+period	O
+interaction	O
+existed	O
+for	O
+liver	O
+TG	O
+and	O
+serum	O
+dextran	O
+precipitable	O
+cholesterol	O
+concentrations	O
+.	O
+
+Liver	O
+TG	O
+and	O
+serum	O
+NEFA	O
+concentrations	O
+were	O
+positively	O
+correlated	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+nerve	O
+and	O
+roots	O
+differ	O
+considerably	O
+both	O
+in	O
+the	O
+force	O
+they	O
+sustain	O
+before	O
+failure	O
+and	O
+in	O
+the	O
+other	O
+biomechanics	O
+they	O
+exhibit	O
+.	O
+
+When	O
+the	O
+coronary	O
+sinus	O
+pressure	O
+reached	O
+15	O
+torr	O
+,	O
+there	O
+was	O
+a	O
+significant	O
+decrease	O
+in	O
+cardiac	O
+index	O
+(	O
+3	O
+.	O
+60	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+to	O
+2	O
+.	O
+70	O
++	O
+/	O
+-	O
+0	O
+.	O
+6	O
+L	O
+/	O
+min	O
+/	O
+m2	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+,	O
+coronary	O
+blood	O
+flow	O
+(	O
+13	O
+.	O
+7	O
++	O
+/	O
+-	O
+3	O
+.	O
+1	O
+to	O
+7	O
+.	O
+0	O
++	O
+/	O
+-	O
+2	O
+.	O
+1	O
+ml	O
+/	O
+min	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+,	O
+rate	O
+of	O
+rise	O
+of	O
+left	O
+ventricular	O
+pressure	O
+(	O
+1	O
+,	O
+567	O
++	O
+/	O
+-	O
+275	O
+to	O
+1	O
+,	O
+331	O
++	O
+/	O
+-	O
+314	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+,	O
+and	O
+an	O
+increase	O
+in	O
+coronary	O
+arteriovenous	O
+difference	O
+(	O
+62	O
+.	O
+8	O
+%	O
++	O
+/	O
+-	O
+9	O
+.	O
+3	O
+%	O
+to	O
+70	O
+.	O
+5	O
+%	O
++	O
+/	O
+-	O
+5	O
+.	O
+4	O
+%	O
+saturation	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+03	O
+)	O
+.	O
+
+Calcifications	O
+in	O
+the	O
+thoracic	O
+aorta	O
+at	O
+the	O
+level	O
+of	O
+the	O
+11th	O
+and	O
+the	O
+12th	O
+thoracic	O
+vertebrae	O
+in	O
+592	O
+men	O
+and	O
+333	O
+women	O
+were	O
+studied	O
+using	O
+computed	O
+tomography	O
+.	O
+
+In	O
+a	O
+series	O
+of	O
+402	O
+consecutive	O
+autopsies	O
+,	O
+parietal	O
+pleural	O
+plaques	O
+(	O
+PP	O
+)	O
+were	O
+found	O
+in	O
+68	O
+individuals	O
+above	O
+40	O
+years	O
+of	O
+age	O
+.	O
+
+Approximately	O
+60	O
+%	O
+of	O
+cell	O
+bodies	O
+of	O
+primary	O
+neurons	O
+innervating	O
+the	O
+intra	O
+and	O
+perioral	O
+structures	O
+through	O
+the	O
+inferior	O
+alveolar	O
+,	O
+lingual	O
+,	O
+mental	O
+,	O
+and	O
+buccal	O
+nerves	O
+were	O
+in	O
+the	O
+range	O
+between	O
+300	O
+and	O
+600	O
+micron	O
+2	O
+in	O
+cross	O
+-	O
+sectional	O
+area	O
+:	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+509	O
++	O
+/	O
+-	O
+243	O
+micron	O
+2	O
+,	O
+420	O
++	O
+/	O
+-	O
+181	O
+micron	O
+2	O
+,	O
+469	O
++	O
+/	O
+-	O
+200	O
+micron	O
+2	O
+,	O
+and	O
+444	O
++	O
+/	O
+-	O
+186	O
+micron	O
+2	O
+,	O
+respectively	O
+.	O
+
+Pharmacological	O
+action	O
+of	O
+eptazocine	O
+(	O
+l	O
+-	O
+1	O
+,	O
+4	O
+-	O
+dimethyl	O
+-	O
+10	O
+-	O
+hydroxy	O
+-	O
+2	O
+,	O
+3	O
+,	O
+4	O
+,	O
+5	O
+,	O
+6	O
+,	O
+7	O
+-	O
+hexahydro	O
+-	O
+1	O
+,	O
+6	O
+-	O
+methano	O
+-	O
+1H	O
+-	O
+4	O
+-	O
+benz	O
+azonine	O
+)	O
+.	O
+
+On	O
+transition	O
+from	O
+high	O
+to	O
+low	O
+voltage	O
+there	O
+was	O
+a	O
+significant	O
+fall	O
+in	O
+arterial	O
+pressure	O
+(	O
+7	O
+%	O
+)	O
+and	O
+an	O
+increase	O
+in	O
+flow	O
+(	O
+19	O
+-	O
+38	O
+%	O
+)	O
+to	O
+areas	O
+of	O
+the	O
+brain	O
+corresponding	O
+to	O
+the	O
+arborization	O
+of	O
+the	O
+reticular	O
+formation	O
+,	O
+i	O
+.	O
+e	O
+.	O
+excluding	O
+the	O
+cerebrum	O
+and	O
+cerebellum	O
+.	O
+
+One	O
+hundred	O
+and	O
+four	O
+(	O
+14	O
+per	O
+cent	O
+)	O
+second	O
+primary	O
+tumours	O
+were	O
+reported	O
+.	O
+
+Failures	O
+of	O
+colorimetric	O
+additivity	O
+under	O
+these	O
+experimental	O
+conditions	O
+are	O
+discussed	O
+.	O
+
+There	O
+have	O
+been	O
+five	O
+problems	O
+(	O
+extravasation	O
+2	O
+,	O
+suspected	O
+sepsis	O
+1	O
+,	O
+and	O
+hematoma	O
+2	O
+)	O
+during	O
+a	O
+total	O
+of	O
+2	O
+,	O
+927	O
+days	O
+of	O
+exposure	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+these	O
+results	O
+may	O
+raise	O
+the	O
+interesting	O
+possibility	O
+of	O
+providing	O
+a	O
+means	O
+of	O
+identifying	O
+greater	O
+or	O
+lesser	O
+susceptibility	O
+to	O
+the	O
+coronary	O
+effects	O
+of	O
+Type	O
+A	O
+behavior	O
+.	O
+
+Two	O
+studies	O
+assessed	O
+two	O
+types	O
+of	O
+reliability	O
+of	O
+the	O
+student	O
+Jenkins	O
+Activity	O
+Survey	O
+(	O
+JAS	O
+;	O
+a	O
+questionnaire	O
+measure	O
+of	O
+Type	O
+A	O
+behavior	O
+)	O
+.	O
+
+When	O
+phencyclidine	O
+was	O
+administered	O
+alone	O
+,	O
+overall	O
+response	O
+rate	O
+decreased	O
+and	O
+percent	O
+errors	O
+increased	O
+with	O
+increasing	O
+doses	O
+.	O
+
+Possibilities	O
+and	O
+outlook	O
+for	O
+wrist	O
+joint	O
+endoprosthesis	O
+
+Study	O
+of	O
+the	O
+energy	O
+metabolism	O
+of	O
+the	O
+sensomotor	O
+cortex	O
+and	O
+hippocampus	O
+by	O
+the	O
+(	O
+14C	O
+)	O
+2	O
+-	O
+deoxyglucose	O
+method	O
+during	O
+the	O
+development	O
+of	O
+dissociated	O
+states	O
+
+Malignant	O
+lymphoma	O
+is	O
+very	O
+heterogeneous	O
+in	O
+terms	O
+of	O
+its	O
+biological	O
+behavior	O
+.	O
+
+Further	O
+investigations	O
+are	O
+necessary	O
+to	O
+elucidate	O
+the	O
+biochemical	O
+and	O
+physiological	O
+properties	O
+of	O
+DLIS	O
+.	O
+
+Among	O
+them	O
+,	O
+26	O
+cases	O
+were	O
+benign	O
+and	O
+34	O
+malignant	O
+.	O
+
+Of	O
+the	O
+cases	O
+with	O
+PLD	O
+,	O
+50	O
+%	O
+had	O
+associated	O
+renal	O
+cysts	O
+and	O
+10	O
+%	O
+of	O
+the	O
+cases	O
+with	O
+APCD	O
+had	O
+associated	O
+liver	O
+cysts	O
+.	O
+
+Fast	O
+goal	O
+-	O
+directed	O
+voluntary	O
+movements	O
+of	O
+the	O
+human	O
+upper	O
+extremity	O
+are	O
+known	O
+to	O
+be	O
+associated	O
+with	O
+three	O
+distinct	O
+bursts	O
+of	O
+EMG	O
+activity	O
+in	O
+antagonistic	O
+muscles	O
+.	O
+
+The	O
+combination	O
+of	O
+F1	O
+and	O
+F2	O
+which	O
+was	O
+the	O
+best	O
+predictor	O
+of	O
+CHD	O
+in	O
+this	O
+population	O
+(	O
+G1	O
+)	O
+might	O
+be	O
+interpreted	O
+as	O
+reflecting	O
+trunk	O
+adiposity	O
+mainly	O
+abdominal	O
+.	O
+
+Renal	O
+clearance	O
+fell	O
+from	O
+19	O
+.	O
+0	O
++	O
+/	O
+-	O
+4	O
+.	O
+9	O
+ml	O
+/	O
+min	O
+/	O
+1	O
+.	O
+73	O
+m2	O
+(	O
+group	O
+I	O
+)	O
+to	O
+1	O
+.	O
+0	O
++	O
+/	O
+-	O
+0	O
+.	O
+4	O
+ml	O
+/	O
+min	O
+/	O
+1	O
+.	O
+73	O
+m2	O
+(	O
+group	O
+IV	O
+)	O
+.	O
+
+The	O
+relations	O
+between	O
+type	O
+A	O
+behavior	O
+,	O
+clinically	O
+relevant	O
+behavior	O
+,	O
+academic	O
+achievement	O
+,	O
+and	O
+IQ	O
+in	O
+children	O
+.	O
+
+She	O
+also	O
+had	O
+slight	O
+weakness	O
+of	O
+the	O
+upper	O
+extremities	O
+.	O
+
+Results	O
+of	O
+electron	O
+therapy	O
+of	O
+tumors	O
+in	O
+different	O
+sites	O
+
+The	O
+mechanism	O
+of	O
+action	O
+is	O
+explored	O
+in	O
+some	O
+detail	O
+,	O
+specifically	O
+as	O
+it	O
+relates	O
+to	O
+reticuloendothelial	O
+system	O
+(	O
+RES	O
+)	O
+Fc	B-GENE
+receptor	I-GENE
+blockade	O
+and	O
+suppression	O
+of	O
+antiplatelet	O
+antibody	O
+synthesis	O
+.	O
+
+Incidences	O
+of	O
+nonfatal	O
+stroke	O
+,	O
+myocardial	O
+infarction	O
+,	O
+angina	O
+pectoris	O
+und	O
+left	O
+ventricular	O
+hypertrophy	O
+could	O
+also	O
+be	O
+lowered	O
+.	O
+
+High	O
+radial	O
+r	O
+values	O
+with	O
+small	O
+standard	O
+deviations	O
+were	O
+observed	O
+in	O
+normal	O
+LV	O
+(	O
+0	O
+.	O
+972	O
++	O
+/	O
+-	O
+0	O
+.	O
+016	O
+)	O
+and	O
+in	O
+non	O
+-	O
+MI	O
+regions	O
+(	O
+0	O
+.	O
+964	O
++	O
+/	O
+-	O
+0	O
+.	O
+018	O
+)	O
+,	O
+indicating	O
+temporally	O
+homogeneous	O
+radial	O
+shortening	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+during	O
+pregnancy	O
+there	O
+are	O
+increases	O
+in	O
+bone	O
+formation	O
+rates	O
+contributing	O
+to	O
+the	O
+increases	O
+in	O
+skeletal	O
+mass	O
+.	O
+
+We	O
+analyzed	O
+data	O
+from	O
+56	O
+patients	O
+with	O
+Systemic	O
+Lupus	O
+Erythematosus	O
+(	O
+SLE	O
+)	O
+in	O
+whom	O
+renal	O
+biopsies	O
+were	O
+done	O
+systematically	O
+.	O
+
+Prevention	O
+by	O
+a	O
+heparin	O
+-	O
+antithrombin	B-GENE
+III	I-GENE
+combination	O
+
+MICs	O
+of	O
+four	O
+antifungal	O
+agents	O
+(	O
+5	O
+-	O
+fluorocytosine	O
+,	O
+miconazole	O
+,	O
+ketoconazole	O
+,	O
+and	O
+amphotericin	O
+B	O
+)	O
+for	O
+84	O
+clinical	O
+isolates	O
+of	O
+various	O
+Candida	O
+species	O
+were	O
+then	O
+determined	O
+with	O
+both	O
+media	O
+in	O
+agar	O
+dilution	O
+and	O
+microtiter	O
+broth	O
+dilution	O
+systems	O
+.	O
+
+There	O
+were	O
+18	O
+patients	O
+with	O
+Group	O
+II	O
+(	O
+a	O
+)	O
+tumors	O
+;	O
+although	O
+tumor	O
+biopsy	O
+was	O
+attempted	O
+on	O
+eight	O
+of	O
+these	O
+,	O
+pathological	O
+diagnosis	O
+at	O
+the	O
+time	O
+of	O
+surgery	O
+was	O
+made	O
+in	O
+only	O
+one	O
+case	O
+.	O
+
+Evidence	O
+that	O
+opiate	O
+addiction	O
+is	O
+in	O
+part	O
+an	O
+immune	O
+response	O
+.	O
+
+Parasitological	O
+post	O
+-	O
+mortem	O
+examination	O
+of	O
+all	O
+seropositive	O
+animals	O
+showed	O
+five	O
+and	O
+seven	O
+false	O
+-	O
+positive	O
+animals	O
+when	O
+E	B-GENE
+/	I-GENE
+S	I-GENE
+and	I-GENE
+CWE	I-GENE
+antigens	I-GENE
+were	O
+used	O
+,	O
+respectively	O
+.	O
+
+Glucocorticoid	O
+induced	O
+hypertension	O
+has	O
+been	O
+regarded	O
+as	O
+independent	O
+of	O
+sodium	O
+(	O
+Na	O
+)	O
+,	O
+in	O
+contrast	O
+to	O
+mineralocorticoid	O
+induced	O
+hypertension	O
+,	O
+which	O
+is	O
+Na	O
++	O
+-	O
+dependent	O
+.	O
+
+Seventeen	O
+of	O
+them	O
+were	O
+on	O
+treatment	O
+with	O
+systemic	O
+steroids	O
+.	O
+
+Examples	O
+of	O
+its	O
+use	O
+in	O
+the	O
+intensive	O
+therapy	O
+unit	O
+are	O
+described	O
+.	O
+
+Only	O
+seven	O
+patients	O
+,	O
+five	O
+of	O
+whom	O
+have	O
+metastatic	O
+disease	O
+,	O
+survive	O
+more	O
+than	O
+10	O
+years	O
+after	O
+first	O
+presentation	O
+;	O
+nine	O
+patients	O
+,	O
+one	O
+of	O
+whom	O
+has	O
+secondaries	O
+,	O
+survive	O
+for	O
+5	O
+years	O
+or	O
+less	O
+.	O
+
+Although	O
+differences	O
+were	O
+not	O
+significant	O
+,	O
+infants	O
+in	O
+the	O
+experimental	O
+group	O
+had	O
+more	O
+changes	O
+in	O
+the	O
+intermittent	O
+mandatory	O
+ventilation	O
+(	O
+IMV	O
+)	O
+settings	O
+during	O
+transport	O
+,	O
+and	O
+more	O
+such	O
+infants	O
+arrived	O
+at	O
+the	O
+receiving	O
+hospital	O
+with	O
+acceptable	O
+pH	O
+and	O
+PCO2	O
+values	O
+.	O
+
+Repetitive	O
+sequences	O
+are	O
+present	O
+in	O
+at	O
+least	O
+three	O
+introns	O
+of	O
+the	O
+cytochrome	B-GENE
+P	I-GENE
+-	I-GENE
+450PBc2	I-GENE
+gene	I-GENE
+,	O
+but	O
+not	O
+in	O
+exons	O
+or	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+.	O
+
+A	O
+large	O
+increase	O
+of	O
+serum	O
+ketones	O
+occurred	O
+under	O
+all	O
+conditions	O
+,	O
+and	O
+the	O
+exercise	O
+respiratory	O
+quotient	O
+suggested	O
+some	O
+increase	O
+of	O
+fat	O
+utilization	O
+,	O
+WW	O
+(	O
+0	O
+.	O
+85	O
+)	O
+through	O
+CW	O
+(	O
+0	O
+.	O
+84	O
+)	O
+to	O
+CC	O
+(	O
+0	O
+.	O
+83	O
+)	O
+.	O
+
+This	O
+lack	O
+of	O
+correlation	O
+may	O
+be	O
+due	O
+to	O
+variations	O
+in	O
+the	O
+metabolic	O
+activity	O
+of	O
+the	O
+endometriotic	O
+implants	O
+present	O
+at	O
+different	O
+stages	O
+of	O
+the	O
+disease	O
+.	O
+
+Respiratory	O
+adaptation	O
+to	O
+chronic	O
+hypoxia	O
+in	O
+newborn	O
+rats	O
+.	O
+
+Compound	O
+1	O
+is	O
+either	O
+21	O
+-	O
+O	O
+-	O
+angeloyl	O
+,	O
+22	O
+-	O
+O	O
+-	O
+tigloyl	O
+R1	O
+-	O
+barrigenol	O
+,	O
+or	O
+21	O
+-	O
+O	O
+-	O
+tigloyl	O
+,	O
+22	O
+-	O
+O	O
+-	O
+angeloyl	O
+R1	O
+-	O
+barrigenol	O
+.	O
+
+Human	O
+and	O
+Chinese	B-GENE
+hamster	I-GENE
+S14	I-GENE
+protein	I-GENE
+sequences	I-GENE
+deduced	O
+from	O
+the	O
+cDNAs	O
+are	O
+identical	O
+.	O
+
+RPS14	B-GENE
+introns	O
+3	O
+and	O
+4	O
+both	O
+contain	O
+Alu	B-GENE
+sequences	O
+.	O
+
+One	O
+of	O
+the	O
+most	O
+relevant	O
+aspects	O
+in	O
+achieving	O
+the	O
+consistent	O
+survival	O
+of	O
+an	O
+animal	O
+undergoing	O
+the	O
+experimental	O
+implantation	O
+of	O
+a	O
+total	O
+artificial	O
+heart	O
+is	O
+obviously	O
+related	O
+to	O
+the	O
+correct	O
+anatomic	O
+placement	O
+of	O
+prosthetic	O
+ventricles	O
+inside	O
+the	O
+chest	O
+.	O
+
+An	O
+exaggerated	O
+tissue	O
+response	O
+adjacent	O
+to	O
+the	O
+cyanoacrylate	O
+site	O
+suggested	O
+a	O
+potential	O
+toxic	O
+chemical	O
+or	O
+thermal	O
+reaction	O
+,	O
+or	O
+both	O
+,	O
+to	O
+the	O
+tissue	O
+adhesive	O
+,	O
+but	O
+there	O
+was	O
+no	O
+evidence	O
+of	O
+any	O
+distant	O
+ocular	O
+effects	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+there	O
+may	O
+be	O
+a	O
+relationship	O
+between	O
+the	O
+pathogenesis	O
+of	O
+MAL	O
+,	O
+narcolepsy	O
+,	O
+and	O
+OSA	O
+.	O
+
+Among	O
+82	O
+superficial	O
+lesions	O
+34	O
+were	O
+classified	O
+as	O
+showing	O
+CR	O
+and	O
+another	O
+23	O
+as	O
+showing	O
+PR	O
+,	O
+with	O
+a	O
+response	O
+rate	O
+of	O
+69	O
+.	O
+5	O
+%	O
+.	O
+
+While	O
+the	O
+examiner	O
+observed	O
+the	O
+interior	O
+of	O
+the	O
+eye	O
+with	O
+indirect	O
+ophthalmoscopy	O
+,	O
+the	O
+point	O
+source	O
+of	O
+light	O
+from	O
+the	O
+fiberoptic	O
+light	O
+pipe	O
+was	O
+moved	O
+along	O
+the	O
+margins	O
+of	O
+the	O
+episcleral	O
+plaque	O
+.	O
+
+These	O
+fusion	O
+proteins	O
+also	O
+allowed	O
+the	O
+localization	O
+of	O
+the	O
+transcriptional	O
+activation	O
+and	O
+DNA	O
+binding	O
+domains	O
+of	O
+the	O
+ToxR	B-GENE
+protein	I-GENE
+to	O
+its	O
+cytoplasmically	O
+located	O
+N	O
+-	O
+terminal	O
+portion	O
+.	O
+
+From	O
+life	O
+-	O
+table	O
+analyses	O
+of	O
+these	O
+patients	O
+,	O
+we	O
+estimated	O
+that	O
+the	O
+incidence	O
+of	O
+secondary	O
+chondrosarcoma	O
+in	O
+patients	O
+who	O
+have	O
+Ollier	O
+disease	O
+is	O
+about	O
+25	O
+per	O
+cent	O
+at	O
+the	O
+age	O
+of	O
+forty	O
+years	O
+,	O
+and	O
+that	O
+malignant	O
+degeneration	O
+is	O
+almost	O
+a	O
+certainty	O
+in	O
+patients	O
+who	O
+have	O
+Maffucci	O
+syndrome	O
+.	O
+
+The	O
+lethal	O
+toxicity	O
+of	O
+inorganic	O
+(	O
+HgCl2	O
+)	O
+and	O
+organic	O
+(	O
+CH3HgCl	O
+)	O
+mercury	O
+chloride	O
+was	O
+compared	O
+for	O
+Coturnix	O
+(	O
+Japanese	O
+quail	O
+,	O
+Coturnix	O
+japonica	O
+)	O
+of	O
+different	O
+ages	O
+from	O
+hatch	O
+through	O
+adulthood	O
+by	O
+single	O
+-	O
+dose	O
+acute	O
+oral	O
+and	O
+intramuscular	O
+injections	O
+and	O
+by	O
+a	O
+5	O
+-	O
+d	O
+dietary	O
+trial	O
+.	O
+
+Since	O
+the	O
+integrated	O
+13h00	O
+-	O
+16h00	O
+plasma	O
+cortisol	O
+estimation	O
+is	O
+cheaper	O
+and	O
+simpler	O
+than	O
+the	O
+mean	O
+13h00	O
+-	O
+16h00	O
+plasma	O
+cortisol	O
+estimation	O
+,	O
+we	O
+recommend	O
+it	O
+as	O
+an	O
+adjunct	O
+in	O
+the	O
+diagnosis	O
+of	O
+Cushing	O
+'	O
+s	O
+syndrome	O
+.	O
+
+Most	O
+of	O
+the	O
+patients	O
+had	O
+locally	O
+advanced	O
+lesions	O
+(	O
+63	O
+T3	O
+-	O
+4	O
+:	O
+91	O
+.	O
+5	O
+%	O
+)	O
+according	O
+to	O
+the	O
+adopted	O
+TNM	O
+system	O
+(	O
+Lederman	O
+-	O
+Gadeberg	O
+,	O
+Sisson	O
+-	O
+Jesse	O
+)	O
+.	O
+
+Chlorambucil	O
+and	O
+interferon	B-GENE
+for	O
+low	O
+grade	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphoma	O
+.	O
+
+Selenium	O
+(	O
+.	O
+1	O
+ppm	O
+)	O
+and	O
+E	O
+(	O
+50	O
+IU	O
+/	O
+kg	O
+)	O
+supplementation	O
+of	O
+the	O
+diet	O
+of	O
+the	O
+sow	O
+increased	O
+plasma	O
+tocopherol	O
+and	O
+Se	O
+concentrations	O
+,	O
+but	O
+did	O
+not	O
+increase	O
+plasma	B-GENE
+glutathione	I-GENE
+peroxidase	I-GENE
+(	O
+GSH	B-GENE
+-	I-GENE
+Px	I-GENE
+)	O
+activity	O
+.	O
+
+Framingham	O
+Type	O
+A	O
+behavior	O
+was	O
+positively	O
+associated	O
+with	O
+diastolic	O
+blood	O
+pressure	O
+(	O
+r	O
+=	O
+0	O
+.	O
+17	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+among	O
+the	O
+women	O
+.	O
+
+The	O
+in	O
+vitro	O
+antibacterial	O
+potency	O
+is	O
+greatest	O
+when	O
+the	O
+1	O
+-	O
+substituent	O
+is	O
+2	O
+,	O
+4	O
+-	O
+difluorophenyl	O
+and	O
+the	O
+7	O
+-	O
+substituent	O
+is	O
+a	O
+3	O
+-	O
+amino	O
+-	O
+1	O
+-	O
+pyrrolidinyl	O
+group	O
+.	O
+
+The	O
+M	B-GENE
+reading	I-GENE
+frame	I-GENE
+differed	O
+from	O
+the	O
+reported	O
+sequence	O
+by	O
+a	O
+single	O
+nucleotide	O
+corresponding	O
+to	O
+a	O
+conservative	O
+lysine	O
+to	O
+arginine	O
+amino	O
+acid	O
+substitution	O
+near	O
+the	O
+carboxy	O
+-	O
+terminus	O
+conserved	O
+among	O
+the	O
+M	B-GENE
+proteins	I-GENE
+of	O
+paramyxoviruses	O
+.	O
+
+An	O
+ion	O
+chromatographic	O
+method	O
+was	O
+used	O
+to	O
+determine	O
+Br	O
+ion	O
+in	O
+the	O
+urine	O
+of	O
+Greyhounds	O
+.	O
+
+II	O
+.	O
+
+Laryngographic	O
+changes	O
+following	O
+endotracheal	O
+intubation	O
+in	O
+adults	O
+.	O
+
+Autotransplantation	O
+of	O
+a	O
+vein	O
+segment	O
+with	O
+valve	O
+in	O
+the	O
+treatment	O
+of	O
+deep	O
+vein	O
+valvular	O
+insufficiency	O
+of	O
+the	O
+lower	O
+extremity	O
+
+The	O
+relationships	O
+among	O
+four	O
+descriptors	O
+of	O
+lactate	O
+increase	O
+:	O
+lactate	O
+threshold	O
+(	O
+LT	O
+)	O
+(	O
+the	O
+VO2	O
+at	O
+which	O
+blood	O
+lactate	O
+concentration	O
+begins	O
+to	O
+increase	O
+above	O
+the	O
+resting	O
+level	O
+during	O
+an	O
+incremental	O
+exercise	O
+test	O
+)	O
+,	O
+LT1	O
+(	O
+the	O
+VO2	O
+at	O
+which	O
+blood	O
+lactate	O
+increases	O
+1	O
+mM	O
+above	O
+the	O
+resting	O
+level	O
+)	O
+,	O
+LT2	O
+(	O
+the	O
+VO2	O
+at	O
+which	O
+blood	O
+lactate	O
+concentration	O
+reaches	O
+a	O
+fixed	O
+value	O
+of	O
+2	O
+mM	O
+)	O
+,	O
+onset	O
+of	O
+blood	O
+lactate	O
+accumulation	O
+(	O
+OBLA	O
+;	O
+the	O
+VO2	O
+at	O
+which	O
+blood	O
+lactate	O
+reaches	O
+a	O
+concentration	O
+of	O
+4	O
+mM	O
+)	O
+,	O
+were	O
+compared	O
+with	O
+aerobic	O
+capacity	O
+(	O
+VO2max	O
+)	O
+and	O
+12	O
+min	O
+running	O
+performance	O
+in	O
+19	O
+untrained	O
+female	O
+students	O
+.	O
+
+This	O
+is	O
+based	O
+on	O
+partitioning	O
+an	O
+underlying	O
+multivariate	O
+normal	O
+distribution	O
+.	O
+
+The	O
+observation	O
+of	O
+late	O
+effects	O
+after	O
+irradiations	O
+or	O
+after	O
+space	O
+flights	O
+show	O
+the	O
+difficulties	O
+encountered	O
+in	O
+assessing	O
+radiative	O
+risks	O
+during	O
+long	O
+duration	O
+space	O
+flights	O
+.	O
+
+Practical	O
+use	O
+and	O
+interpretation	O
+of	O
+viral	O
+hepatitis	O
+B	O
+markers	O
+and	O
+hepatic	O
+biopsy	O
+in	O
+HBs	B-GENE
+Ag	I-GENE
+carriers	O
+and	O
+at	O
+the	O
+chronic	O
+hepatitis	O
+stage	O
+
+The	O
+1	O
+,	O
+2	O
+,	O
+3	O
+and	O
+4	O
+year	O
+survival	O
+rates	O
+were	O
+94	O
+%	O
+,	O
+84	O
+%	O
+,	O
+76	O
+%	O
+and	O
+63	O
+%	O
+,	O
+respectively	O
+.	O
+
+Northern	O
+blotting	O
+with	O
+a	O
+unique	O
+17	O
+-	O
+mer	O
+oligonucleotide	O
+demonstrated	O
+the	O
+absence	O
+of	O
+the	O
+mutant	O
+sequence	O
+in	O
+the	O
+mRNA	O
+from	O
+which	O
+the	O
+cDNA	O
+library	O
+giving	O
+rise	O
+to	O
+the	O
+mutant	O
+cDNA	O
+was	O
+constructed	O
+.	O
+
+Chemotherapy	O
+of	O
+metastasizing	O
+breast	O
+cancer	O
+
+In	O
+recent	O
+years	O
+,	O
+successful	O
+physiological	O
+models	O
+have	O
+been	O
+developed	O
+for	O
+a	O
+variety	O
+of	O
+volatile	O
+and	O
+nonvolatile	O
+chemicals	O
+,	O
+and	O
+their	O
+ability	O
+to	O
+perform	O
+the	O
+extrapolations	O
+needed	O
+in	O
+risk	O
+assessment	O
+has	O
+been	O
+demonstrated	O
+.	O
+
+Linear	O
+extrapolation	O
+is	O
+used	O
+below	O
+the	O
+experimental	O
+data	O
+range	O
+to	O
+establish	O
+an	O
+upper	O
+bound	O
+on	O
+carcinogenic	O
+risk	O
+at	O
+low	O
+doses	O
+.	O
+
+Hisako	O
+Minowa	O
+who	O
+has	O
+worked	O
+as	O
+a	O
+psychiatric	O
+counsellor	O
+in	O
+industry	O
+for	O
+the	O
+past	O
+20	O
+years	O
+
+Deletion	O
+mapping	O
+studies	O
+revealed	O
+that	O
+the	O
+upstream	O
+DNA	O
+sequences	O
+up	O
+to	O
+-	O
+86	O
+were	O
+sufficient	O
+for	O
+the	O
+optimal	O
+basal	O
+level	O
+transcription	O
+in	O
+HeLa	O
+cells	O
+and	O
+also	O
+for	O
+the	O
+EIA	B-GENE
+-	O
+induced	O
+transcription	O
+.	O
+
+Incorporation	O
+of	O
+the	O
+polyene	O
+antibiotic	O
+amphotericin	O
+B	O
+(	O
+AMB	O
+)	O
+in	O
+liposomes	O
+results	O
+in	O
+a	O
+marked	O
+reduction	O
+in	O
+drug	O
+toxicity	O
+with	O
+no	O
+loss	O
+of	O
+antifungal	O
+potency	O
+.	O
+
+Eleven	O
+healthy	O
+,	O
+normotensive	O
+males	O
+undergoing	O
+routine	O
+restorative	O
+dental	O
+care	O
+were	O
+evaluated	O
+during	O
+treatment	O
+for	O
+possible	O
+hemodynamic	O
+alterations	O
+in	O
+response	O
+to	O
+potential	O
+sympathetic	O
+nervous	O
+system	O
+stimulation	O
+.	O
+
+Serum	B-GENE
+IgM	I-GENE
+and	O
+IgE	B-GENE
+concentrations	O
+,	O
+allergen	B-GENE
+-	I-GENE
+specific	I-GENE
+IgE	I-GENE
+scores	O
+,	O
+and	O
+the	O
+tumor	O
+E2R	B-GENE
+status	O
+were	O
+combined	O
+to	O
+construct	O
+a	O
+three	O
+-	O
+level	O
+risk	O
+classification	O
+that	O
+was	O
+more	O
+prognostic	O
+than	O
+any	O
+of	O
+the	O
+individual	O
+components	O
+.	O
+
+Within	O
+the	O
+Strep	O
+.	O
+mutans	O
+group	O
+there	O
+was	O
+a	O
+highly	O
+-	O
+significant	O
+difference	O
+between	O
+Strep	O
+.	O
+mutans	O
+/	O
+Strep	O
+.	O
+cricetus	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+with	O
+respect	O
+to	O
+mean	O
+clump	O
+size	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+T	O
+.	O
+C	O
+.	O
+,	O
+LDL	B-GENE
+-	I-GENE
+C	I-GENE
+.	O
+,	O
+HDL	B-GENE
+-	I-GENE
+C	I-GENE
+.	O
+,	O
+HDL2	B-GENE
+-	I-GENE
+C	I-GENE
+.	O
+,	O
+apo	B-GENE
+B	I-GENE
+,	O
+apo	B-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+/	I-GENE
+B	I-GENE
+ratio	O
+and	O
+apo	B-GENE
+A	I-GENE
+-	I-GENE
+II	I-GENE
+/	I-GENE
+B	I-GENE
+ratio	O
+are	O
+predictive	O
+risk	O
+factors	O
+of	O
+the	O
+coronary	O
+heart	O
+disease	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+the	O
+unique	O
+suppository	O
+formulation	O
+of	O
+CZX	O
+-	O
+S	O
+is	O
+useful	O
+in	O
+the	O
+treatment	O
+of	O
+infections	O
+in	O
+children	O
+with	O
+heavy	O
+psychophysiologic	O
+disorders	O
+and	O
+in	O
+children	O
+who	O
+cannot	O
+take	O
+oral	O
+drugs	O
+because	O
+of	O
+severe	O
+vomiting	O
+.	O
+
+Single	O
+photon	O
+emission	O
+computerized	O
+tomography	O
+(	O
+SPECT	O
+)	O
+,	O
+by	O
+providing	O
+three	O
+-	O
+dimensional	O
+representation	O
+of	O
+myocardial	O
+Tl	O
+-	O
+201	O
+,	O
+offers	O
+promise	O
+for	O
+improved	O
+localization	O
+of	O
+CAD	O
+.	O
+
+Computer	O
+assisted	O
+mapping	O
+in	O
+quantitative	O
+analysis	O
+of	O
+cerebral	O
+positron	O
+emission	O
+tomograms	O
+.	O
+
+Documentation	O
+of	O
+a	O
+successful	O
+intrauterine	O
+fertilization	O
+with	O
+delivery	O
+of	O
+a	O
+term	O
+baby	O
+supports	O
+the	O
+theoretical	O
+feasibility	O
+of	O
+the	O
+EP	O
+;	O
+however	O
+,	O
+anovulation	O
+incurred	O
+by	O
+our	O
+procedure	O
+appears	O
+to	O
+be	O
+the	O
+major	O
+drawback	O
+.	O
+
+MRI	O
+disclosed	O
+one	O
+or	O
+more	O
+of	O
+the	O
+following	O
+abnormalities	O
+in	O
+24	O
+(	O
+63	O
+%	O
+)	O
+of	O
+38	O
+treated	O
+kidneys	O
+:	O
+(	O
+1	O
+)	O
+loss	O
+of	O
+corticomedullary	O
+differentiation	O
+,	O
+(	O
+2	O
+)	O
+perirenal	O
+fluid	O
+,	O
+(	O
+3	O
+)	O
+subcapsular	O
+hematoma	O
+,	O
+(	O
+4	O
+)	O
+hemorrhage	O
+into	O
+a	O
+renal	O
+cyst	O
+,	O
+and	O
+(	O
+5	O
+)	O
+unexplained	O
+abnormalities	O
+.	O
+
+The	O
+results	O
+obtained	O
+are	O
+similar	O
+to	O
+those	O
+described	O
+with	O
+the	O
+previous	O
+Cremophor	O
+formulation	O
+although	O
+greater	O
+variability	O
+in	O
+induction	O
+and	O
+recovery	O
+times	O
+was	O
+noted	O
+with	O
+the	O
+emulsion	O
+formulation	O
+.	O
+
+The	O
+percentage	O
+RFR	O
+reduction	O
+at	O
+the	O
+end	O
+of	O
+CPB	O
+showed	O
+significant	O
+correlation	O
+with	O
+1	O
+)	O
+CPB	O
+duration	O
+(	O
+r	O
+=	O
+0	O
+.	O
+49	O
+)	O
+,	O
+2	O
+)	O
+oxygen	O
+flow	O
+rate	O
+index	O
+(	O
+OFRI	O
+)	O
+,	O
+i	O
+.	O
+e	O
+.	O
+flow	O
+/	O
+min	O
+in	O
+the	O
+bubble	O
+oxygenator	O
+/	O
+m2	O
+bsa	O
+(	O
+r	O
+=	O
+0	O
+.	O
+38	O
+)	O
+,	O
+and	O
+3	O
+)	O
+blood	O
+flow	O
+rate	O
+index	O
+(	O
+BFRI	O
+)	O
+,	O
+i	O
+.	O
+e	O
+.	O
+average	O
+volume	O
+of	O
+blood	O
+pumped	O
+through	O
+the	O
+heart	O
+-	O
+lung	O
+machine	O
+/	O
+min	O
+CPB	O
+time	O
+/	O
+m2	O
+bsa	O
+(	O
+r	O
+=	O
+0	O
+.	O
+51	O
+)	O
+.	O
+
+Diagnosis	O
+of	O
+unilateral	O
+renal	O
+artery	O
+lesions	O
+after	O
+captopril	O
+administration	O
+.	O
+
+A	O
+retrospective	O
+study	O
+of	O
+banked	O
+sera	O
+from	O
+19	O
+cats	O
+with	O
+the	O
+eosinophilic	O
+granuloma	O
+complex	O
+revealed	O
+that	O
+68	O
+%	O
+of	O
+affected	O
+cats	O
+had	O
+circulating	O
+antibodies	O
+to	O
+components	O
+of	O
+normal	O
+cat	O
+epithelium	O
+.	O
+
+In	O
+memory	O
+of	O
+Magdelaine	O
+Comtesse	O
+
+These	O
+results	O
+suggest	O
+that	O
+indoramin	O
+may	O
+have	O
+Class	O
+III	O
+antiarrhythmic	O
+activity	O
+.	O
+
+A	O
+high	O
+efficacy	O
+of	O
+the	O
+combined	O
+use	O
+of	O
+nontoxic	O
+doses	O
+of	O
+two	O
+pharmaceuticals	O
+:	O
+cystamine	O
+(	O
+50	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+mexamine	O
+(	O
+25	O
+mg	O
+/	O
+kg	O
+)	O
+under	O
+the	O
+conditions	O
+of	O
+short	O
+-	O
+term	O
+exogenous	O
+hypoxia	O
+(	O
+7	O
+.	O
+5	O
+%	O
+O2	O
+)	O
+was	O
+found	O
+in	O
+(	O
+CBA	O
+X	O
+C57Bl	O
+)	O
+F1	O
+mice	O
+.	O
+
+The	O
+Mean	O
+was	O
+74	O
+,	O
+3	O
++	O
+/	O
+-	O
+53	O
+,	O
+6	O
+micrograms	O
+J	O
+/	O
+g	O
+Cr	O
+,	O
+the	O
+Median	O
+61	O
+micrograms	O
+J	O
+/	O
+g	O
+Cr	O
+.	O
+
+In	O
+the	O
+region	O
+Walgau	O
+with	O
+mixed	O
+industrial	O
+-	O
+rural	O
+population	O
+an	O
+iodine	O
+deficiency	O
+I	O
+was	O
+found	O
+in	O
+81	O
+%	O
+and	O
+an	O
+iodine	O
+deficiency	O
+II	O
+in	O
+45	O
+%	O
+.	O
+
+The	O
+structural	O
+gene	O
+for	O
+hydrogenase	B-GENE
+encodes	O
+a	O
+protein	O
+product	O
+of	O
+molecular	O
+mass	O
+45820	O
+Da	O
+.	O
+
+Pancreaticoduodenal	O
+lymph	O
+node	O
+enlargement	O
+,	O
+regardless	O
+of	O
+cause	O
+,	O
+has	O
+been	O
+a	O
+source	O
+of	O
+imaging	O
+confusion	O
+because	O
+of	O
+its	O
+propensity	O
+to	O
+mimic	O
+pancreatic	O
+malignancy	O
+yet	O
+not	O
+cause	O
+biliary	O
+obstruction	O
+.	O
+
+Interference	O
+with	O
+rheumatoid	B-GENE
+factor	I-GENE
+was	O
+only	O
+observed	O
+in	O
+the	O
+ELISA	O
+enzygnost	O
+if	O
+sera	O
+were	O
+not	O
+pretreated	O
+with	O
+latex	O
+adsorbents	O
+.	O
+
+All	O
+patients	O
+had	O
+elevated	O
+levels	O
+of	O
+serum	B-GENE
+IgE	I-GENE
+antibodies	I-GENE
+to	O
+the	O
+crude	O
+soybean	O
+extract	O
+;	O
+binding	O
+values	O
+ranged	O
+from	O
+2	O
+.	O
+3	O
+to	O
+28	O
+.	O
+1	O
+times	O
+that	O
+of	O
+a	O
+negative	O
+control	O
+serum	O
+.	O
+
+New	O
+techniques	O
+for	O
+the	O
+mass	O
+spectrometry	O
+of	O
+natural	O
+products	O
+.	O
+
+Dual	O
+radionuclide	O
+subtraction	O
+imaging	O
+of	O
+the	O
+spleen	O
+using	O
+67Ga	O
+citrate	O
+and	O
+99mTc	O
+is	O
+useful	O
+in	O
+further	O
+delineating	O
+lesions	O
+that	O
+are	O
+identified	O
+on	O
+either	O
+a	O
+routine	O
+radiogallium	O
+survey	O
+or	O
+on	O
+a	O
+conventional	O
+sulfur	O
+colloid	O
+liver	O
+-	O
+spleen	O
+image	O
+.	O
+
+Nursing	O
+education	O
+-	O
+-	O
+the	O
+computer	O
+obligation	O
+.	O
+
+Shear	O
+bond	O
+strength	O
+of	O
+a	O
+composite	O
+resin	O
+to	O
+an	O
+etched	O
+glass	O
+ionomer	O
+.	O
+
+An	O
+additional	O
+advantage	O
+is	O
+that	O
+the	O
+resin	O
+can	O
+be	O
+removed	O
+and	O
+the	O
+immunoperoxidase	B-GENE
+technique	O
+carried	O
+out	O
+on	O
+thin	O
+sections	O
+.	O
+
+Such	O
+a	O
+concept	O
+is	O
+crucial	O
+to	O
+our	O
+understanding	O
+of	O
+the	O
+pathology	O
+of	O
+ageing	O
+in	O
+general	O
+.	O
+
+We	O
+consider	O
+that	O
+DIL	O
+-	O
+CP	O
+is	O
+a	O
+safe	O
+and	O
+excellent	O
+CP	O
+in	O
+CABG	O
+surgery	O
+and	O
+we	O
+are	O
+now	O
+utilizing	O
+this	O
+CP	O
+in	O
+all	O
+patients	O
+requiring	O
+CABG	O
+surgery	O
+.	O
+
+We	O
+have	O
+earlier	O
+evolved	O
+an	O
+experimental	O
+model	O
+by	O
+means	O
+of	O
+which	O
+changes	O
+identical	O
+to	O
+the	O
+microembolism	O
+syndrome	O
+can	O
+be	O
+induced	O
+from	O
+a	O
+reproducible	O
+musculo	O
+-	O
+skeletal	O
+trauma	O
+in	O
+pigs	O
+observed	O
+under	O
+long	O
+-	O
+term	O
+anesthesia	O
+under	O
+standardized	O
+conditions	O
+.	O
+
+Although	O
+no	O
+statistical	O
+significance	O
+was	O
+achieved	O
+,	O
+it	O
+is	O
+remarkable	O
+that	O
+there	O
+was	O
+a	O
+clear	O
+trend	O
+for	O
+the	O
+superiority	O
+of	O
+Galphimia	O
+D6	O
+while	O
+the	O
+Galphimia	O
+dilution	O
+10	O
+(	O
+-	O
+6	O
+)	O
+was	O
+about	O
+equally	O
+effective	O
+compared	O
+with	O
+placebo	O
+.	O
+
+The	O
+volume	O
+of	O
+blood	O
+to	O
+the	O
+flap	O
+ranges	O
+from	O
+1	O
+to	O
+2	O
+ml	O
+/	O
+min	O
+,	O
+collateral	O
+circulation	O
+to	O
+the	O
+flap	O
+exists	O
+,	O
+but	O
+is	O
+negligible	O
+,	O
+and	O
+there	O
+is	O
+little	O
+change	O
+in	O
+the	O
+capillary	O
+blood	O
+flow	O
+as	O
+the	O
+flap	O
+ages	O
+.	O
+
+With	O
+aging	O
+,	O
+many	O
+aspects	O
+of	O
+immune	O
+function	O
+change	O
+.	O
+
+Oral	O
+candidiasis	O
+
+In	O
+addition	O
+,	O
+the	O
+gcd1	B-GENE
+-	I-GENE
+101	I-GENE
+mutation	I-GENE
+suppressed	O
+the	O
+low	O
+translational	O
+efficiency	O
+of	O
+GCN4	B-GENE
+-	O
+lacZ	B-GENE
+mRNA	O
+observed	O
+in	O
+gcn2	B-GENE
+-	I-GENE
+and	O
+gcn3	B-GENE
+-	I-GENE
+cells	O
+.	O
+
+This	O
+suggests	O
+that	O
+alaproclate	O
+acutely	O
+increases	O
+the	O
+responsiveness	O
+of	O
+postsynaptic	O
+muscarinic	B-GENE
+and	I-GENE
+alpha	I-GENE
+1	I-GENE
+adrenoceptors	I-GENE
+.	O
+
+The	O
+distribution	O
+of	O
+patients	O
+was	O
+as	O
+follows	O
+:	O
+group	O
+1	O
+-	O
+-	O
+complex	O
+gamma	O
+-	O
+therapy	O
+(	O
+55	O
+cases	O
+)	O
+,	O
+group	O
+2	O
+-	O
+-	O
+complex	O
+gamma	O
+-	O
+therapy	O
+plus	O
+iliac	O
+lymphadenectomy	O
+(	O
+50	O
+cases	O
+)	O
+and	O
+group	O
+3	O
+-	O
+-	O
+complex	O
+radiation	O
+treatment	O
+with	O
+megavolt	O
+bremsstrahlung	O
+beam	O
+from	O
+the	O
+luc	O
+type	O
+installation	O
+and	O
+iliac	O
+lymphadenectomy	O
+(	O
+50	O
+cases	O
+)	O
+.	O
+
+The	O
+availability	O
+of	O
+cryoprecipitate	O
+and	O
+DDAVP	O
+offers	O
+an	O
+alternative	O
+and	O
+effective	O
+treatment	O
+for	O
+the	O
+temporary	O
+reversal	O
+of	O
+uremic	O
+bleeding	O
+in	O
+patients	O
+who	O
+require	O
+urgent	O
+invasive	O
+procedures	O
+.	O
+
+Thrombophlebitis	O
+and	O
+pulmonary	O
+embolism	O
+in	O
+congenital	O
+factor	B-GENE
+XII	I-GENE
+deficiency	O
+
+Biopsies	O
+of	O
+the	O
+jejunal	O
+mucosa	O
+have	O
+shown	O
+abnormal	O
+enzyme	O
+activity	O
+or	O
+deficiencies	O
+in	O
+transport	O
+mechanisms	O
+.	O
+
+Laboratory	O
+pyrolyses	O
+have	O
+indeed	O
+shown	O
+that	O
+PCBs	O
+give	O
+significant	O
+yields	O
+of	O
+PCDFs	O
+,	O
+and	O
+chlorobenzenes	O
+give	O
+both	O
+PCDFs	O
+and	O
+PCDDs	O
+.	O
+
+A	O
+significant	O
+degree	O
+of	O
+homology	O
+was	O
+also	O
+found	O
+among	O
+these	O
+genes	O
+and	O
+the	O
+Mtase	B-GENE
+gene	I-GENE
+of	O
+related	O
+phage	O
+SPR	O
+,	O
+which	O
+codes	O
+for	O
+an	O
+enzyme	O
+with	O
+different	O
+modification	O
+specificity	O
+.	O
+
+In	O
+a	O
+blind	O
+controlled	O
+trial	O
+,	O
+15	O
+patients	O
+with	O
+COCM	O
+(	O
+NYHA	O
+II	O
+-	O
+III	O
+)	O
+with	O
+sinus	O
+rhythm	O
+and	O
+a	O
+left	O
+ventricular	O
+ejection	O
+fraction	O
+(	O
+LV	O
+-	O
+EF	O
+)	O
+of	O
+34	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+.	O
+6	O
+%	O
+received	O
+consecutively	O
+D	O
+(	O
+0	O
+.	O
+25	O
+-	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+d	O
+)	O
+,	O
+placebo	O
+(	O
+PLAC	O
+)	O
+,	O
+P	O
+(	O
+slow	O
+releases	O
+=	O
+SR	O
+)	O
+(	O
+80	O
+mg	O
+/	O
+d	O
+SR	O
+)	O
+and	O
+both	O
+drugs	O
+combined	O
+in	O
+respective	O
+doses	O
+.	O
+
+Mild	O
+orbital	O
+discomfort	O
+occurred	O
+in	O
+some	O
+patients	O
+.	O
+
+The	O
+sample	O
+is	O
+deproteinized	O
+and	O
+after	O
+centrifugation	O
+valproic	O
+acid	O
+in	O
+the	O
+supernatant	O
+is	O
+measured	O
+in	O
+the	O
+free	O
+form	O
+by	O
+direct	O
+injection	O
+into	O
+the	O
+gas	O
+chromatograph	O
+.	O
+
+Changes	O
+in	O
+muscarinic	B-GENE
+acetylcholine	I-GENE
+receptors	I-GENE
+in	O
+guinea	O
+-	O
+pig	O
+lung	O
+:	O
+effects	O
+of	O
+aging	O
+,	O
+inhalation	O
+of	O
+an	O
+allergen	O
+,	O
+administration	O
+of	O
+drugs	O
+,	O
+and	O
+vagotomy	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+other	O
+stabilizers	O
+,	O
+increased	O
+sucrose	O
+can	O
+provide	O
+increased	O
+thermoresistance	O
+to	O
+the	O
+virus	O
+in	O
+2	O
+.	O
+5	O
+%	O
+albumin	B-GENE
+.	O
+
+The	O
+overall	O
+prevalence	O
+of	O
+psoriasis	O
+was	O
+4	O
+.	O
+79	O
+%	O
+in	O
+men	O
+and	O
+4	O
+.	O
+85	O
+%	O
+in	O
+women	O
+.	O
+
+Greek	O
+classicism	O
+in	O
+living	O
+structure	O
+?	O
+Some	O
+deductive	O
+pathways	O
+in	O
+animal	O
+morphology	O
+.	O
+
+The	O
+possible	O
+origin	O
+and	O
+role	O
+of	O
+CSF	B-GENE
+prolactin	I-GENE
+are	O
+discussed	O
+.	O
+
+Three	O
+chromosomal	B-GENE
+crsA	I-GENE
+mutations	I-GENE
+,	O
+crsA1	B-GENE
+,	O
+crsA4	B-GENE
+,	O
+and	O
+crsA47	B-GENE
+,	O
+were	O
+transferred	O
+by	O
+the	O
+"	O
+gene	O
+conversion	O
+"	O
+process	O
+to	O
+B	O
+.	O
+subtilis	O
+plasmid	O
+pRPD11	O
+,	O
+which	O
+consists	O
+of	O
+the	O
+entire	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+rpoD	I-GENE
+coding	I-GENE
+sequence	I-GENE
+,	O
+encoding	O
+the	O
+major	B-GENE
+sigma	I-GENE
+43	I-GENE
+factor	I-GENE
+of	I-GENE
+B	I-GENE
+.	I-GENE
+subtilis	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+,	O
+and	O
+pUB110	O
+.	O
+
+Selective	O
+effect	O
+of	O
+pulmonary	O
+oedema	O
+on	O
+prostaglandin	O
+E2	O
+pharmacokinetics	O
+in	O
+rat	O
+lung	O
+.	O
+
+This	O
+article	O
+will	O
+briefly	O
+review	O
+the	O
+published	O
+data	O
+on	O
+the	O
+morphology	O
+,	O
+function	O
+,	O
+and	O
+biochemistry	O
+of	O
+the	O
+normal	O
+renal	O
+medulla	O
+and	O
+the	O
+pathology	O
+associated	O
+with	O
+RPN	O
+,	O
+together	O
+with	O
+the	O
+secondary	O
+changes	O
+which	O
+give	O
+rise	O
+to	O
+cortical	O
+degeneration	O
+or	O
+epithelial	O
+carcinoma	O
+.	O
+
+The	O
+data	O
+indicate	O
+that	O
+the	O
+five	O
+different	O
+(	O
+and	O
+partially	O
+overlapping	O
+)	O
+sry	B-GENE
+messenger	I-GENE
+RNAs	I-GENE
+detectable	O
+in	O
+early	O
+embryos	O
+are	O
+initiated	O
+at	O
+three	O
+separate	O
+sites	O
+,	O
+each	O
+directly	O
+upstream	O
+from	O
+one	O
+of	O
+the	O
+three	O
+protein	O
+-	O
+coding	O
+regions	O
+,	O
+designated	O
+(	O
+in	O
+5	O
+'	O
+to	O
+3	O
+'	O
+order	O
+)	O
+beta	O
+,	O
+alpha	O
+and	O
+delta	O
+.	O
+
+Chronic	O
+thyroiditis	O
+as	O
+a	O
+risk	O
+factor	O
+of	O
+B	O
+-	O
+cell	O
+lymphoma	O
+in	O
+the	O
+thyroid	O
+gland	O
+.	O
+
+Plasma	B-GENE
+secretin	I-GENE
+levels	O
+also	O
+augmented	O
+after	O
+the	O
+administration	O
+of	O
+ethanol	O
+solutions	O
+,	O
+with	O
+a	O
+delay	O
+of	O
+about	O
+one	O
+hour	O
+after	O
+the	O
+onset	O
+of	O
+acid	O
+secretion	O
+.	O
+
+Spectrophotometric	O
+microanalysis	O
+of	O
+ethylenediaminotetracetic	O
+acid	O
+in	O
+pharmaceutical	O
+preparations	O
+
+A	O
+comparison	O
+among	O
+the	O
+5	O
+'	O
+flanking	O
+regions	O
+encompassing	O
+the	O
+presumptive	O
+HS	B-GENE
+promoter	I-GENE
+of	O
+the	O
+soybean	B-GENE
+HS	I-GENE
+-	I-GENE
+protein	I-GENE
+genes	I-GENE
+demonstrated	O
+this	O
+region	O
+to	O
+be	O
+extremely	O
+homologous	O
+.	O
+
+Using	O
+this	O
+method	O
+,	O
+we	O
+measured	O
+absorption	O
+of	O
+low	O
+doses	O
+of	O
+vitamin	O
+A	O
+,	O
+which	O
+may	O
+provide	O
+a	O
+more	O
+physiological	O
+approach	O
+to	O
+assessment	O
+of	O
+fat	O
+malabsorption	O
+.	O
+
+Fulminant	O
+hepatitis	O
+A	O
+in	O
+chronic	O
+HBV	O
+carrier	O
+.	O
+
+During	O
+this	O
+time	O
+,	O
+the	O
+patients	O
+all	O
+had	O
+the	O
+characteristic	O
+plasma	O
+thyroid	O
+hormone	O
+changes	O
+associated	O
+with	O
+amiodarone	O
+therapy	O
+,	O
+i	O
+.	O
+e	O
+.	O
+increased	O
+T4	O
+,	O
+free	O
+T4	O
+,	O
+and	O
+rT3	O
+and	O
+decreased	O
+T3	O
+,	O
+while	O
+remaining	O
+clinically	O
+euthyroid	O
+.	O
+
+Drug	O
+and	O
+nutrient	O
+interactions	O
+.	O
+
+In	O
+each	O
+compartment	O
+O2	O
+is	O
+removed	O
+by	O
+the	O
+tissues	O
+as	O
+a	O
+chemical	O
+reaction	O
+takes	O
+place	O
+between	O
+O2	O
+and	O
+oxyhemoglobin	B-GENE
+(	O
+HbO2	B-GENE
+)	O
+.	O
+
+To	O
+evaluate	O
+the	O
+effects	O
+of	O
+propranolol	O
+on	O
+myocardial	O
+metabolism	O
+after	O
+coronary	O
+reperfusion	O
+,	O
+serial	O
+measurements	O
+of	O
+myocardial	B-GENE
+creatine	I-GENE
+kinase	I-GENE
+(	O
+CK	B-GENE
+)	O
+and	O
+calcium	O
+(	O
+Ca	O
+)	O
+contents	O
+and	O
+CK	B-GENE
+and	O
+lactic	O
+acid	O
+(	O
+LA	O
+)	O
+concentrations	O
+in	O
+coronary	O
+sinus	O
+blood	O
+were	O
+carried	O
+out	O
+in	O
+33	O
+open	O
+-	O
+chest	O
+dogs	O
+.	O
+
+Cortisol	O
+excretion	O
+,	O
+appeared	O
+to	O
+be	O
+markedly	O
+affected	O
+by	O
+the	O
+season	O
+although	O
+other	O
+factors	O
+such	O
+as	O
+social	O
+and	O
+environmental	O
+stress	O
+cannot	O
+be	O
+discounted	O
+.	O
+
+Two	O
+studies	O
+on	O
+the	O
+relationship	O
+between	O
+taking	O
+a	O
+commercial	O
+coaching	O
+course	O
+and	O
+performance	O
+on	O
+the	O
+Medical	O
+College	O
+Admission	O
+Test	O
+(	O
+MCAT	O
+)	O
+are	O
+reported	O
+.	O
+
+A	O
+total	O
+of	O
+90	O
+patients	O
+were	O
+randomly	O
+allocated	O
+either	O
+to	O
+an	O
+MY	O
+-	O
+1	O
+treated	O
+or	O
+an	O
+untreated	O
+group	O
+.	O
+
+Below	O
+50	O
+%	O
+decrease	O
+of	O
+PaO2	O
+,	O
+NADH	O
+was	O
+reduced	O
+largely	O
+.	O
+
+Angiography	O
+was	O
+performed	O
+following	O
+the	O
+rCBF	O
+study	O
+and	O
+the	O
+degree	O
+of	O
+vasospasm	O
+was	O
+measured	O
+on	O
+the	O
+angiograms	O
+.	O
+
+The	O
+financial	O
+impact	O
+of	O
+childhood	O
+asthma	O
+has	O
+not	O
+been	O
+assessed	O
+since	O
+Vance	O
+and	O
+Taylor	O
+reported	O
+their	O
+data	O
+in	O
+Annals	O
+of	O
+Allergy	O
+13	O
+years	O
+ago	O
+.	O
+
+Hypersplenism	O
+
+Electrical	O
+activity	O
+was	O
+evaluated	O
+by	O
+monitoring	O
+the	O
+general	O
+electrocorticogram	O
+(	O
+ECoG	O
+)	O
+as	O
+well	O
+as	O
+local	O
+DC	O
+steady	O
+potential	O
+(	O
+two	O
+sites	O
+)	O
+.	O
+
+The	O
+topography	O
+and	O
+trajectories	O
+of	O
+the	O
+commissural	O
+fibers	O
+of	O
+the	O
+superior	O
+temporal	O
+region	O
+(	O
+STR	O
+)	O
+are	O
+studied	O
+using	O
+the	O
+autoradiographic	O
+technique	O
+.	O
+
+The	O
+diabetic	O
+state	O
+was	O
+characterized	O
+by	O
+mild	O
+insulin	B-GENE
+deficiency	O
+,	O
+plasma	O
+levels	O
+being	O
+73	O
+%	O
+of	O
+controls	O
+,	O
+and	O
+mild	O
+hyperglycemia	O
+,	O
+with	O
+nonfasting	O
+plasma	O
+glucose	O
+levels	O
+of	O
+1	O
+.	O
+5	O
+times	O
+normal	O
+.	O
+
+No	O
+consistent	O
+correlation	O
+between	O
+blood	O
+pressure	O
+change	O
+and	O
+SCR	O
+-	O
+change	O
+was	O
+seen	O
+.	O
+
+Shoulder	O
+forearm	O
+support	O
+for	O
+the	O
+subluxed	O
+shoulder	O
+.	O
+
+Piroxicam	O
+produced	O
+a	O
+lower	O
+incidence	O
+of	O
+gastric	O
+ulcers	O
+than	O
+equivalent	O
+doses	O
+of	O
+indomethacin	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+both	O
+in	O
+the	O
+early	O
+stages	O
+(	O
+0T	O
+,	O
+0N	O
+)	O
+and	O
+in	O
+more	O
+severe	O
+stages	O
+of	O
+VWF	O
+(	O
+stages	O
+1	O
+-	O
+2	O
+)	O
+cold	O
+induced	O
+hyperreactivity	O
+in	O
+the	O
+digital	O
+vessels	O
+and	O
+Raynaud	O
+'	O
+s	O
+syndrome	O
+are	O
+vascular	O
+disorders	O
+of	O
+functional	O
+origin	O
+occurring	O
+without	O
+any	O
+prethrombotic	O
+alterations	O
+.	O
+
+In	O
+MCCP	O
+functions	O
+of	O
+the	O
+source	O
+emission	O
+,	O
+surface	O
+reflection	O
+,	O
+photoacceptor	O
+sensitivity	O
+are	O
+approximated	O
+by	O
+the	O
+normal	O
+distribution	O
+curves	O
+.	O
+
+To	O
+assess	O
+the	O
+effects	O
+of	O
+alveolar	O
+hypoxia	O
+and	O
+angiotensin	B-GENE
+II	I-GENE
+infusion	O
+on	O
+distribution	O
+of	O
+blood	O
+flow	O
+to	O
+the	O
+lung	O
+we	O
+performed	O
+perfusion	O
+lung	O
+scans	O
+on	O
+anesthetized	O
+mechanically	O
+ventilated	O
+lambs	O
+.	O
+
+A	O
+flow	O
+rate	O
+of	O
+at	O
+least	O
+5	O
+mL	O
+/	O
+h	O
+is	O
+required	O
+through	O
+the	O
+receptor	O
+(	O
+volume	O
+,	O
+0	O
+.	O
+4	O
+mL	O
+)	O
+for	O
+accurate	O
+results	O
+.	O
+
+We	O
+have	O
+now	O
+located	O
+the	O
+5	O
+'	O
+ends	O
+of	O
+the	O
+two	O
+remaining	O
+late	O
+mRNAs	O
+.	O
+
+The	O
+efficacy	O
+of	O
+quantitative	O
+and	O
+qualitative	O
+chloride	O
+titrators	O
+in	O
+the	O
+estimation	O
+of	O
+human	O
+salt	O
+intake	O
+.	O
+
+Doctor	O
+Berglund	O
+warns	O
+members	O
+of	O
+union	O
+pitfalls	O
+.	O
+
+Acute	O
+appearance	O
+of	O
+hemiparesis	O
+or	O
+hemiplegia	O
+with	O
+initial	O
+marked	O
+spasticity	O
+was	O
+observed	O
+in	O
+8	O
+stroke	O
+patients	O
+.	O
+
+Recurrent	O
+acute	O
+rhinosinusitis	O
+was	O
+common	O
+in	O
+both	O
+groups	O
+of	O
+patients	O
+,	O
+but	O
+the	O
+development	O
+of	O
+chronic	O
+rhinosinusitis	O
+was	O
+only	O
+found	O
+in	O
+patients	O
+with	O
+CVID	O
+,	O
+indicating	O
+the	O
+more	O
+severe	O
+nature	O
+of	O
+this	O
+condition	O
+compared	O
+with	O
+selective	O
+IgA	B-GENE
+deficiency	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+AP	B-GENE
+-	I-GENE
+A	I-GENE
+may	O
+be	O
+potentially	O
+useful	O
+in	O
+the	O
+management	O
+of	O
+heart	O
+failure	O
+.	O
+
+The	O
+various	O
+muscles	O
+of	O
+the	O
+pelvic	O
+floor	O
+region	O
+could	O
+be	O
+reflexly	O
+activated	O
+either	O
+individually	O
+or	O
+as	O
+a	O
+mass	O
+unit	O
+depending	O
+on	O
+the	O
+intensity	O
+of	O
+stimulation	O
+.	O
+
+The	O
+frequency	O
+of	O
+lactase	B-GENE
+phenotypes	I-GENE
+in	O
+Aymara	O
+children	O
+.	O
+
+Activities	O
+of	O
+hepatic	O
+cytochrome	B-GENE
+P	I-GENE
+-	I-GENE
+450	I-GENE
+-	O
+dependent	O
+metabolizing	O
+enzymes	O
+such	O
+as	O
+aminopyrine	B-GENE
+-	I-GENE
+and	I-GENE
+TMO	I-GENE
+N	I-GENE
+-	I-GENE
+demethylase	I-GENE
+and	O
+aniline	B-GENE
+hydroxylase	I-GENE
+activity	O
+were	O
+decreased	O
+by	O
+pretreatment	O
+of	O
+rats	O
+with	O
+cimetidine	O
+,	O
+whereas	O
+in	O
+the	O
+rats	O
+pretreated	O
+with	O
+ranitidine	O
+,	O
+these	O
+enzyme	O
+activities	O
+were	O
+not	O
+changed	O
+.	O
+
+Doxorubicin	O
+,	O
+dacarbazine	O
+,	O
+vincristine	O
+,	O
+and	O
+cyclophosphamide	O
+in	O
+the	O
+treatment	O
+of	O
+advanced	O
+gastrointestinal	O
+leiomyosarcoma	O
+.	O
+
+The	O
+effect	O
+of	O
+the	O
+opiate	O
+antagonist	O
+naloxone	O
+was	O
+evaluated	O
+in	O
+11	O
+unselected	O
+patients	O
+with	O
+cerebral	O
+ischemia	O
+.	O
+
+Electrochemical	O
+detection	O
+of	O
+depressed	O
+circulating	O
+levels	O
+of	O
+vitamin	O
+K1	O
+in	O
+osteoporosis	O
+.	O
+
+In	O
+the	O
+present	O
+experiments	O
+,	O
+we	O
+investigate	O
+the	O
+role	O
+played	O
+by	O
+the	O
+temporal	O
+pattern	O
+of	O
+neural	O
+activity	O
+during	O
+the	O
+ontogeny	O
+of	O
+frequency	O
+tuning	O
+in	O
+the	O
+mouse	O
+central	O
+auditory	O
+system	O
+.	O
+
+Ultrastructure	O
+of	O
+the	O
+tumor	O
+in	O
+1	O
+patient	O
+in	O
+whom	O
+transurethral	O
+resection	O
+was	O
+performed	O
+2	O
+weeks	O
+after	O
+alum	O
+irrigation	O
+revealed	O
+well	O
+preserved	O
+nuclear	O
+chromatin	O
+,	O
+thus	O
+,	O
+suggesting	O
+that	O
+whatever	O
+changes	O
+occur	O
+after	O
+alum	O
+irrigation	O
+are	O
+short	O
+-	O
+lived	O
+.	O
+
+The	O
+generally	O
+adopted	O
+criteria	O
+enabling	O
+to	O
+classify	O
+the	O
+examined	O
+persons	O
+into	O
+the	O
+following	O
+3	O
+groups	O
+have	O
+been	O
+used	O
+:	O
+(	O
+a	O
+)	O
+diseased	O
+of	O
+BEN	O
+;	O
+(	O
+b	O
+)	O
+suspect	O
+to	O
+be	O
+diseased	O
+of	O
+BEN	O
+,	O
+and	O
+(	O
+c	O
+)	O
+individuals	O
+without	O
+signs	O
+of	O
+a	O
+renal	O
+disease	O
+.	O
+
+The	O
+POEMS	O
+syndrome	O
+(	O
+Polyneuropathy	O
+,	O
+Organomegaly	O
+,	O
+Endocrinopathy	O
+,	O
+Monoclonal	O
+component	O
+,	O
+Skin	O
+)	O
+.	O
+
+During	O
+a	O
+disease	O
+remission	O
+there	O
+was	O
+an	O
+increase	O
+in	O
+GAG	O
+secretion	O
+with	O
+urine	O
+,	O
+linked	O
+with	O
+hyperheparinuria	O
+(	O
+13	O
+.	O
+1	O
+-	O
+fold	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+In	O
+metastasis	O
+-	O
+free	O
+patients	O
+,	O
+the	O
+best	O
+results	O
+were	O
+obtained	O
+with	O
+tumor	O
+diameters	O
+under	O
+2	O
+cm	O
+regardless	O
+of	O
+their	O
+localization	O
+in	O
+lung	O
+tissue	O
+and	O
+with	O
+2	O
+-	O
+-	O
+4	O
+.	O
+9	O
+cm	O
+tumors	O
+embedded	O
+in	O
+lung	O
+parenchyma	O
+.	O
+
+Two	O
+siblings	O
+with	O
+hemolytic	O
+anemia	O
+caused	O
+by	O
+triosephosphate	B-GENE
+isomerase	I-GENE
+deficiency	O
+developed	O
+a	O
+progressive	O
+neurological	O
+syndrome	O
+featuring	O
+dystonic	O
+movements	O
+,	O
+tremor	O
+,	O
+pyramidal	O
+tract	O
+signs	O
+,	O
+and	O
+evidence	O
+of	O
+spinal	O
+motor	O
+neuron	O
+involvement	O
+.	O
+
+One	O
+extract	O
+with	O
+the	O
+lowest	O
+PCA	O
+content	O
+was	O
+non	O
+-	O
+carcinogenic	O
+.	O
+
+Aortic	O
+diameters	O
+in	O
+infants	O
+and	O
+young	O
+children	O
+:	O
+normative	O
+angiographic	O
+data	O
+.	O
+
+The	O
+present	O
+investigation	O
+has	O
+revealed	O
+that	O
+the	O
+distribution	O
+of	O
+the	O
+main	O
+fatty	O
+acids	O
+in	O
+Leptospira	O
+phospholipids	O
+is	O
+similar	O
+to	O
+their	O
+distribution	O
+in	O
+Leptospira	O
+neutral	O
+lipids	O
+with	O
+the	O
+exception	O
+of	O
+unsaturated	O
+fatty	O
+acid	O
+with	O
+14	O
+carbon	O
+atoms	O
+,	O
+occurring	O
+mainly	O
+in	O
+phospholipids	O
+.	O
+
+Since	O
+1970	O
+the	O
+frequency	O
+of	O
+potassium	O
+-	O
+induced	O
+ulceration	O
+has	O
+been	O
+low	O
+-	O
+-	O
+3	O
+cases	O
+per	O
+100	O
+000	O
+patient	O
+-	O
+years	O
+of	O
+slow	O
+-	O
+release	O
+tablet	O
+use	O
+.	O
+
+Hydrocortisone	O
+caused	O
+lymphopenia	O
+and	O
+inhibited	O
+the	O
+blastogenic	O
+response	O
+of	O
+peripheral	O
+blood	O
+lymphocytes	O
+to	O
+phytohemagglutinin	B-GENE
+and	O
+concanavalin	B-GENE
+A	I-GENE
+mitogens	O
+.	O
+
+To	O
+test	O
+the	O
+feasibility	O
+of	O
+using	O
+liposomes	O
+to	O
+deliver	O
+therapeutic	O
+agents	O
+to	O
+the	O
+lungs	O
+,	O
+the	O
+effect	O
+of	O
+liposome	O
+-	O
+encapsulated	O
+superoxide	B-GENE
+dismutase	I-GENE
+(	O
+SOD	B-GENE
+)	O
+or	O
+catalase	B-GENE
+on	O
+pulmonary	O
+oxygen	O
+toxicity	O
+was	O
+studied	O
+in	O
+rats	O
+.	O
+
+Marrow	O
+cell	O
+necrosis	O
+in	O
+anorexia	O
+nervosa	O
+and	O
+involuntary	O
+starvation	O
+.	O
+
+For	O
+comparison	O
+conventional	O
+heparin	O
+was	O
+used	O
+during	O
+18	O
+dialyses	O
+in	O
+the	O
+same	O
+patients	O
+.	O
+
+Chenodeoxycholic	O
+acid	O
+(	O
+cheno	O
+)	O
+and	O
+ursodeoxycholic	O
+acid	O
+(	O
+urso	O
+)	O
+dissolve	O
+cholesterol	O
+gallstones	O
+in	O
+man	O
+.	O
+
+Sensory	O
+evoked	O
+field	O
+potentials	O
+were	O
+recorded	O
+from	O
+the	O
+mesencephalic	O
+reticular	O
+formation	O
+(	O
+MRF	O
+)	O
+,	O
+central	O
+gray	O
+(	O
+CG	O
+)	O
+and	O
+somatosensory	O
+cortex	O
+(	O
+SCX	O
+)	O
+,	O
+following	O
+incremental	O
+doses	O
+of	O
+halothane	O
+in	O
+freely	O
+-	O
+moving	O
+rats	O
+.	O
+
+Ultrastructure	O
+of	O
+the	O
+heart	O
+muscle	O
+in	O
+experimental	O
+myocardial	O
+infarct	O
+following	O
+physical	O
+training	O
+
+Pharmacological	O
+desympathization	O
+leads	O
+to	O
+the	O
+development	O
+of	O
+hyper	O
+-	O
+reactivity	O
+of	O
+the	O
+true	O
+pacemakers	O
+to	O
+noradrenaline	O
+and	O
+dopamine	O
+and	O
+triggers	O
+off	O
+changes	O
+in	O
+the	O
+regulation	O
+of	O
+the	O
+electric	O
+activity	O
+of	O
+these	O
+cells	O
+by	O
+catecholamines	O
+.	O
+
+OODG	O
+is	O
+a	O
+diagnostic	O
+method	O
+permitting	O
+assessment	O
+of	O
+ocular	O
+pulse	O
+curves	O
+and	O
+objective	O
+determination	O
+of	O
+blood	O
+pressures	O
+in	O
+the	O
+ophthalmic	O
+circulatory	O
+system	O
+(	O
+retinal	O
+and	O
+ciliary	O
+arterial	O
+blood	O
+pressures	O
+)	O
+simultaneously	O
+for	O
+both	O
+eyes	O
+,	O
+without	O
+dilatation	O
+of	O
+the	O
+pupils	O
+.	O
+
+Viral	O
+infections	O
+have	O
+long	O
+been	O
+suspected	O
+to	O
+be	O
+causative	O
+agents	O
+in	O
+a	O
+number	O
+of	O
+inner	O
+ear	O
+dysfunctions	O
+.	O
+
+55	O
++	O
+/	O
+-	O
+11	O
+%	O
+)	O
+,	O
+all	O
+other	O
+parameters	O
+showed	O
+a	O
+significant	O
+increase	O
+:	O
+RS	O
+index	O
+5	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+mVolt	O
+to	O
+6	O
+.	O
+0	O
++	O
+/	O
+-	O
+1	O
+.	O
+7	O
+mVolt	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+;	O
+EDD	O
+6	O
+.	O
+3	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+to	O
+6	O
+.	O
+8	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+cm	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+;	O
+HV	O
+1017	O
++	O
+/	O
+-	O
+151	O
+ml	O
+to	O
+1099	O
++	O
+/	O
+-	O
+261	O
+ml	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+;	O
+EDV	O
+371	O
++	O
+/	O
+-	O
+131	O
+ml	O
+to	O
+441	O
++	O
+/	O
+-	O
+175	O
+ml	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+;	O
+RBV	O
+117	O
++	O
+/	O
+-	O
+57	O
+ml	O
+to	O
+151	O
++	O
+/	O
+-	O
+77	O
+ml	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Retrospective	O
+analyses	O
+of	O
+this	O
+death	O
+revealed	O
+a	O
+significant	O
+decrease	O
+of	O
+the	O
+left	O
+ventricular	O
+(	O
+LV	O
+)	O
+end	O
+-	O
+diastolic	O
+volume	O
+index	O
+(	O
+EDVI	O
+)	O
+of	O
+21	O
+ml	O
+/	O
+m2	O
+(	O
+36	O
+%	O
+of	O
+normal	O
+)	O
+.	O
+
+In	O
+group	O
+I	O
+adults	O
+both	O
+of	O
+these	O
+variables	O
+increased	O
+.	O
+
+Individual	O
+alcohol	O
+reaction	O
+profiles	O
+.	O
+
+Vitiligo	O
+in	O
+diabetes	O
+mellitus	O
+.	O
+
+The	O
+pharmacokinetics	O
+of	O
+each	O
+tetracycline	O
+in	O
+serum	O
+and	O
+dermal	O
+,	O
+suction	O
+blister	O
+fluid	O
+were	O
+determined	O
+after	O
+oral	O
+doses	O
+of	O
+300	O
+mg	O
+lymecycline	O
+or	O
+100	O
+mg	O
+doxycycline	O
+on	O
+the	O
+3rd	O
+day	O
+.	O
+
+A	O
+high	O
+degree	O
+of	O
+correlation	O
+in	O
+the	O
+sense	O
+of	O
+the	O
+classic	O
+conception	O
+of	O
+brain	O
+localization	O
+of	O
+neuropsychological	O
+syndromes	O
+was	O
+found	O
+.	O
+
+35	O
+patients	O
+with	O
+acute	O
+arterial	O
+occlusions	O
+[	O
+27	O
+]	O
+and	O
+graft	O
+thromboses	O
+[	O
+8	O
+]	O
+,	O
+responsible	O
+for	O
+severe	O
+and	O
+recent	O
+ischemia	O
+,	O
+were	O
+treated	O
+by	O
+fibrinolytic	O
+therapy	O
+(	O
+Urokinase	B-GENE
+:	O
+1	O
+000	O
+units	O
+/	O
+kg	O
+/	O
+hour	O
+,	O
+and	O
+Lys	O
+Plasminogen	B-GENE
+)	O
+.	O
+
+We	O
+conclude	O
+that	O
+androgenic	O
+hormones	O
+reduce	O
+HDL	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+concentrations	O
+and	O
+the	O
+HDL2	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+subfraction	O
+,	O
+possibly	O
+by	O
+enhancing	O
+hepatic	B-GENE
+triglyceride	I-GENE
+lipase	I-GENE
+activity	O
+.	O
+
+Because	O
+of	O
+its	O
+wide	O
+spectrum	O
+of	O
+activity	O
+particularly	O
+against	O
+ampicillin	O
+resistant	O
+strains	O
+of	O
+H	O
+.	O
+influenzae	O
+and	O
+because	O
+of	O
+its	O
+good	O
+tolerance	O
+Cefaclor	O
+is	O
+very	O
+useful	O
+in	O
+treatment	O
+of	O
+respiratory	O
+tract	O
+infections	O
+in	O
+children	O
+.	O
+
+Shape	O
+factor	O
+correlated	O
+well	O
+with	O
+hemodynamic	O
+data	O
+for	O
+RV	O
+/	O
+LV	O
+systolic	O
+pressure	O
+ratios	O
+(	O
+r	O
+=	O
+0	O
+.	O
+93	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+for	O
+normalized	O
+interventricular	O
+pressure	O
+differences	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+95	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+The	O
+effective	O
+and	O
+low	O
+toxic	O
+dose	O
+schedules	O
+of	O
+KW	O
+-	O
+2083	O
+should	O
+be	O
+investigated	O
+further	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+initial	O
+plasma	O
+retinol	O
+level	O
+in	O
+conjunction	O
+with	O
+RBP	B-GENE
+was	O
+found	O
+to	O
+be	O
+even	O
+lower	O
+in	O
+12	O
+patients	O
+(	O
+35	O
+.	O
+1	O
+micrograms	O
+dl	O
+-	O
+1	O
+,	O
+3	O
+.	O
+7	O
+mg	O
+dl	O
+-	O
+1	O
+)	O
+who	O
+subsequently	O
+had	O
+cancer	O
+recurrence	O
+than	O
+in	O
+those	O
+who	O
+remained	O
+free	O
+of	O
+apparent	O
+cancer	O
+(	O
+44	O
+.	O
+5	O
+micrograms	O
+dl	O
+-	O
+1	O
+,	O
+4	O
+.	O
+6	O
+mg	O
+dl	O
+-	O
+1	O
+)	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+:	O
+1	O
+)	O
+the	O
+initial	O
+response	O
+to	O
+tethering	O
+varies	O
+according	O
+to	O
+previous	O
+penning	O
+and	O
+handling	O
+experience	O
+,	O
+2	O
+)	O
+although	O
+the	O
+circadian	O
+rhythm	O
+of	O
+cortisol	O
+was	O
+either	O
+altered	O
+or	O
+disrupted	O
+during	O
+estrus	O
+,	O
+such	O
+disruptions	O
+were	O
+not	O
+influenced	O
+by	O
+type	O
+of	O
+penning	O
+and	O
+3	O
+)	O
+tether	O
+stalls	O
+may	O
+chronically	O
+increase	O
+cortisol	O
+concentrations	O
+in	O
+gilts	O
+.	O
+
+This	O
+laser	O
+provided	O
+sufficient	O
+power	O
+in	O
+an	O
+amniotic	O
+fluid	O
+medium	O
+to	O
+occlude	O
+placental	O
+vessels	O
+as	O
+large	O
+as	O
+7	O
+mm	O
+in	O
+diameter	O
+within	O
+6	O
+seconds	O
+at	O
+a	O
+power	O
+density	O
+of	O
+2000	O
+W	O
+/	O
+cm2	O
+.	O
+
+On	O
+d	O
+112	O
+,	O
+progesterone	O
+was	O
+higher	O
+(	O
+P	O
+less	O
+than	O
+.	O
+05	O
+)	O
+in	O
+hysterectomized	O
+heifers	O
+than	O
+in	O
+other	O
+treatment	O
+groups	O
+.	O
+
+Male	O
+Japanese	O
+quail	O
+were	O
+chronically	O
+exposed	O
+to	O
+5000	O
+ppm	O
+manganese	O
+(	O
+Mn	O
+)	O
+as	O
+particulate	O
+manganese	O
+oxide	O
+(	O
+Mn3O4	O
+)	O
+in	O
+their	O
+diet	O
+from	O
+hatching	O
+to	O
+75	O
+days	O
+of	O
+age	O
+.	O
+
+This	O
+study	O
+indicated	O
+that	O
+the	O
+Japanese	O
+quail	O
+was	O
+less	O
+sensitive	O
+to	O
+particulate	O
+Mn3O4	O
+exposure	O
+than	O
+rodents	O
+treated	O
+comparably	O
+.	O
+
+Plasma	O
+and	O
+bladder	O
+platinum	O
+concentration	O
+were	O
+measured	O
+following	O
+intravesical	O
+DDP	O
+,	O
+and	O
+also	O
+histopathological	O
+examination	O
+,	O
+urinalysis	O
+,	O
+complete	O
+blood	O
+count	O
+and	O
+blood	O
+chemistry	O
+were	O
+performed	O
+in	O
+order	O
+to	O
+know	O
+the	O
+toxicity	O
+of	O
+intravesical	O
+DDP	O
+.	O
+
+Scintigraphic	O
+visualisation	O
+of	O
+Walker	O
+carcinoma	O
+-	O
+256	O
+in	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+by	O
+means	O
+of	O
+99mTc	O
+-	O
+labelled	O
+monocytes	O
+.	O
+
+Rabbit	O
+eyes	O
+were	O
+removed	O
+and	O
+held	O
+in	O
+temperature	O
+-	O
+regulated	O
+chambers	O
+and	O
+irrigated	O
+with	O
+saline	O
+.	O
+
+Before	O
+birth	O
+,	O
+there	O
+were	O
+a	O
+few	O
+perivascular	O
+adrenergic	O
+nerves	O
+and	O
+correspondingly	O
+low	O
+ovarian	O
+NE	O
+levels	O
+.	O
+
+Monitoring	O
+changes	O
+in	O
+the	O
+heart	O
+rate	O
+of	O
+the	O
+premature	O
+fetus	O
+during	O
+tocolysis	O
+with	O
+the	O
+beta	O
+-	O
+adrenomimetics	O
+partusisten	O
+and	O
+Pre	O
+-	O
+par	O
+
+Since	O
+September	O
+1980	O
+to	O
+June	O
+1983	O
+we	O
+have	O
+treated	O
+32	O
+patients	O
+with	O
+ovarian	O
+cancer	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+the	O
+calcium	O
+antagonist	O
+,	O
+diltiazem	O
+,	O
+may	O
+modify	O
+the	O
+effects	O
+of	O
+isoflurane	O
+on	O
+myocardial	O
+function	O
+.	O
+
+Supraventricular	O
+arrhythmias	O
+-	O
+-	O
+digoxin	O
+and	O
+quinidine	O
+revisited	O
+.	O
+
+Visidex	O
+I	O
+is	O
+unsuitable	O
+for	O
+storage	O
+and	O
+re	O
+-	O
+reading	O
+.	O
+
+The	O
+Cox	O
+proportional	O
+hazards	O
+model	O
+was	O
+applied	O
+to	O
+the	O
+data	O
+in	O
+order	O
+to	O
+determine	O
+the	O
+prognostic	O
+factors	O
+for	O
+long	O
+-	O
+term	O
+survival	O
+.	O
+
+This	O
+suggests	O
+that	O
+mechanisms	O
+other	O
+than	O
+an	O
+excessive	O
+increase	O
+in	O
+myocardial	O
+oxygen	O
+demand	O
+may	O
+be	O
+responsible	O
+for	O
+the	O
+many	O
+episodes	O
+occurring	O
+outside	O
+the	O
+hospital	O
+.	O
+
+These	O
+data	O
+showed	O
+:	O
+that	O
+progesterone	O
+secretion	O
+is	O
+pulsatile	O
+throughout	O
+the	O
+human	O
+luteal	O
+phase	O
+,	O
+with	O
+maximum	O
+frequency	O
+in	O
+the	O
+mid	O
+-	O
+luteal	O
+phase	O
+;	O
+that	O
+during	O
+the	O
+mid	O
+-	O
+luteal	O
+phase	O
+most	O
+subjects	O
+had	O
+progesterone	O
+levels	O
+both	O
+above	O
+and	O
+below	O
+currently	O
+accepted	O
+ovulatory	O
+thresholds	O
+;	O
+the	O
+use	O
+of	O
+a	O
+single	O
+measurement	O
+of	O
+progesterone	O
+in	O
+the	O
+mid	O
+-	O
+luteal	O
+phase	O
+is	O
+not	O
+always	O
+a	O
+reliable	O
+indicator	O
+of	O
+ovulation	O
+;	O
+a	O
+threshold	O
+greater	O
+than	O
+20	O
+nmol	O
+/	O
+l	O
+may	O
+yield	O
+an	O
+unacceptable	O
+number	O
+of	O
+false	O
+negative	O
+results	O
+.	O
+
+This	O
+slope	O
+tended	O
+to	O
+be	O
+higher	O
+(	O
+approximately	O
+1	O
+.	O
+6	O
+dB	O
+/	O
+dB	O
+)	O
+for	O
+L1	O
+=	O
+L2	O
+greater	O
+than	O
+80	O
+dB	O
+.	O
+
+Histamine	O
+reactivity	O
+was	O
+significantly	O
+reduced	O
+after	O
+the	O
+nifedipine	O
+aerosol	O
+,	O
+the	O
+geometric	O
+mean	O
+provocative	O
+concentration	O
+causing	O
+a	O
+35	O
+%	O
+fall	O
+in	O
+specific	O
+airway	O
+conductance	O
+,	O
+rising	O
+from	O
+5	O
+.	O
+0	O
+to	O
+10	O
+.	O
+9	O
+mg	O
+/	O
+ml	O
+of	O
+histamine	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Pharmacologic	O
+doses	O
+of	O
+vitamin	O
+B6	O
+administered	O
+to	O
+lactating	O
+women	O
+have	O
+been	O
+reported	O
+to	O
+suppress	O
+plasma	B-GENE
+prolactin	I-GENE
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+but	O
+similar	O
+elevation	O
+of	O
+mean	O
+O2	O
+uptake	O
+during	O
+40	O
+min	O
+postexercise	O
+by	O
+13	O
+.	O
+6	O
+%	O
+in	O
+both	O
+the	O
+fasted	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+and	O
+fed	O
+state	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+In	O
+controls	O
+,	O
+most	O
+of	O
+the	O
+output	O
+from	O
+the	O
+conduit	O
+occurred	O
+during	O
+type	O
+I	O
+activity	O
+(	O
+73	O
++	O
+/	O
+-	O
+14	O
+%	O
+)	O
+.	O
+
+Greater	O
+attenuation	O
+of	O
+the	O
+N1	O
+-	O
+P2	O
+and	O
+baseline	O
+-	O
+P2	O
+amplitude	O
+of	O
+the	O
+probe	O
+EPs	O
+was	O
+observed	O
+when	O
+the	O
+probe	O
+stimulus	O
+was	O
+presented	O
+to	O
+the	O
+right	O
+ear	O
+and	O
+the	O
+verbal	O
+material	O
+presented	O
+to	O
+the	O
+left	O
+ear	O
+than	O
+when	O
+the	O
+opposite	O
+stimulation	O
+arrangement	O
+was	O
+used	O
+.	O
+
+Twenty	O
+-	O
+five	O
+patients	O
+(	O
+80	O
+,	O
+6	O
+%	O
+)	O
+with	O
+mixed	O
+neoplasms	O
+were	O
+operated	O
+on	O
+by	O
+total	O
+conservative	O
+parotidectomy	O
+(	O
+T	O
+.	O
+C	O
+.	O
+P	O
+.	O
+)	O
+,	O
+3	O
+(	O
+9	O
+,	O
+7	O
+%	O
+)	O
+by	O
+S	O
+.	O
+P	O
+.	O
+and	O
+3	O
+(	O
+9	O
+,	O
+7	O
+%	O
+)	O
+by	O
+En	O
+.	O
+
+The	O
+comparisons	O
+revealed	O
+that	O
+female	O
+homicide	O
+-	O
+suicide	O
+perpetrators	O
+were	O
+more	O
+likely	O
+than	O
+female	O
+homicide	O
+-	O
+suicide	O
+victims	O
+to	O
+live	O
+in	O
+mobile	O
+homes	O
+,	O
+kill	O
+their	O
+lover	O
+or	O
+ex	O
+-	O
+lover	O
+,	O
+have	O
+their	O
+crime	O
+accidentally	O
+discovered	O
+,	O
+leave	O
+a	O
+suicide	O
+note	O
+,	O
+kill	O
+on	O
+a	O
+weekend	O
+,	O
+and	O
+be	O
+depressed	O
+,	O
+but	O
+are	O
+less	O
+likely	O
+than	O
+female	O
+homicide	O
+-	O
+suicide	O
+victims	O
+to	O
+live	O
+with	O
+a	O
+spouse	O
+.	O
+
+Germ	O
+-	O
+free	O
+rabbits	O
+given	O
+mouse	O
+CRF	O
+-	O
+flora	O
+showed	O
+values	O
+quite	O
+different	O
+from	O
+control	O
+animals	O
+for	O
+most	O
+parameters	O
+,	O
+indicating	O
+unsuitability	O
+of	O
+mouse	O
+CRF	O
+flora	O
+to	O
+'	O
+normalize	O
+'	O
+rabbits	O
+.	O
+
+The	O
+weak	O
+relationships	O
+between	O
+F	O
+and	O
+Zn	O
+to	O
+Mg	O
+clearly	O
+have	O
+no	O
+significant	O
+effect	O
+on	O
+the	O
+contents	O
+of	O
+these	O
+elements	O
+in	O
+bone	O
+.	O
+
+L3	O
+-	O
+L4	O
+compressive	O
+load	O
+was	O
+calculated	O
+using	O
+a	O
+model	O
+of	O
+the	O
+anatomy	O
+of	O
+the	O
+trunk	O
+musculoskeletal	O
+system	O
+.	O
+
+Component	O
+P100	O
+was	O
+associated	O
+with	O
+a	O
+frontal	O
+negativity	O
+of	O
+similar	O
+latency	O
+favoring	O
+the	O
+hypothesis	O
+of	O
+a	O
+dipolar	O
+occipital	O
+generator	O
+.	O
+
+Although	O
+no	O
+differences	O
+were	O
+noted	O
+in	O
+the	O
+decrease	O
+in	O
+platelet	O
+counts	O
+between	O
+the	O
+two	O
+groups	O
+,	O
+fibrinogen	B-GENE
+levels	O
+and	O
+alpha	B-GENE
+2	I-GENE
+-	I-GENE
+antiplasmin	I-GENE
+levels	O
+declined	O
+less	O
+drastically	O
+in	O
+the	O
+antithrombin	B-GENE
+-	O
+treated	O
+group	O
+.	O
+
+Failure	O
+of	O
+stapedius	O
+reflexometry	O
+in	O
+the	O
+diagnosis	O
+of	O
+myasthenia	O
+gravis	O
+.	O
+
+Factors	O
+influencing	O
+semen	O
+characteristics	O
+in	O
+young	O
+boars	O
+reared	O
+in	O
+a	O
+subtropical	O
+environment	O
+were	O
+studied	O
+.	O
+
+[	O
+14C	O
+]	O
+-	O
+beta	O
+-	O
+phenethylamine	O
+,	O
+its	O
+distribution	O
+after	O
+administration	O
+by	O
+various	O
+routes	O
+to	O
+cats	O
+,	O
+and	O
+the	O
+effects	O
+of	O
+monoamine	B-GENE
+oxidase	I-GENE
+inhibitors	O
+.	O
+
+All	O
+runners	O
+drank	O
+a	O
+total	O
+of	O
+1	O
+.	O
+4	O
+L	O
+of	O
+water	O
+during	O
+the	O
+race	O
+.	O
+
+The	O
+rates	O
+of	O
+total	O
+energy	O
+use	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+=	O
+39	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+vs	O
+35	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+kJ	O
+X	O
+min	O
+-	O
+1	O
+;	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+were	O
+significantly	O
+higher	O
+at	O
+-	O
+10	O
+degrees	O
+C	O
+than	O
+at	O
+22	O
+degrees	O
+C	O
+.	O
+
+Clinical	O
+aspects	O
+and	O
+therapy	O
+
+Following	O
+seven	O
+days	O
+'	O
+incubation	O
+both	O
+at	O
+20	O
+degrees	O
+C	O
+and	O
+28	O
+degrees	O
+C	O
+,	O
+Ae	O
+.	O
+vexans	O
+nip	O
+.	O
+was	O
+capable	O
+of	O
+transmitting	O
+the	O
+virus	O
+.	O
+
+Blood	O
+eosinophils	O
+in	O
+patients	O
+with	O
+Taenia	O
+saginata	O
+taeniasis	O
+.	O
+
+The	O
+recommendation	O
+is	O
+made	O
+that	O
+specific	O
+sub	O
+-	O
+groups	O
+of	O
+attempters	O
+need	O
+to	O
+be	O
+identified	O
+and	O
+may	O
+warrant	O
+specialized	O
+intervention	O
+strategies	O
+.	O
+
+There	O
+was	O
+no	O
+correlation	O
+between	O
+secretor	O
+status	O
+and	O
+clinical	O
+status	O
+,	O
+spirometry	O
+measurements	O
+,	O
+salivary	B-GENE
+and	I-GENE
+serum	I-GENE
+lysozyme	I-GENE
+levels	O
+or	O
+rates	O
+of	O
+respiratory	O
+tract	O
+colonization	O
+with	O
+P	O
+.	O
+aeruginosa	O
+and	O
+S	O
+.	O
+aureus	O
+.	O
+
+There	O
+was	O
+no	O
+correlation	O
+between	O
+secretor	O
+status	O
+and	O
+clinical	O
+status	O
+,	O
+spirometry	O
+measurements	O
+,	O
+salivary	O
+and	O
+serum	B-GENE
+lysozyme	I-GENE
+levels	O
+or	O
+rates	O
+of	O
+respiratory	O
+tract	O
+colonization	O
+with	O
+P	O
+.	O
+aeruginosa	O
+and	O
+S	O
+.	O
+aureus	O
+.	O
+
+Gains	O
+increased	O
+3	O
+.	O
+5	O
+%	O
+(	O
+P	O
+less	O
+than	O
+.	O
+10	O
+)	O
+and	O
+feed	O
+conversion	O
+improved	O
+5	O
+.	O
+9	O
+%	O
+(	O
+P	O
+less	O
+than	O
+.	O
+07	O
+)	O
+in	O
+steers	O
+fed	O
+.	O
+28	O
+%	O
+AS	O
+-	O
+VFA	O
+compared	O
+with	O
+gain	O
+and	O
+feed	O
+conversion	O
+of	O
+the	O
+control	O
+steers	O
+.	O
+
+Daily	O
+and	O
+seasonal	O
+rhythmicity	O
+in	O
+the	O
+methylation	O
+of	O
+pineal	O
+indolic	O
+compounds	O
+in	O
+adult	O
+male	O
+golden	O
+hamsters	O
+,	O
+kept	O
+under	O
+natural	O
+conditions	O
+.	O
+
+The	O
+transit	O
+time	O
+was	O
+significantly	O
+shortened	O
+.	O
+
+Among	O
+the	O
+patients	O
+grades	O
+1	O
+-	O
+2	O
+-	O
+3	O
+,	O
+81	O
+%	O
+had	O
+a	O
+good	O
+out	O
+come	O
+without	O
+any	O
+neurological	O
+abnormality	O
+,	O
+among	O
+the	O
+patients	O
+graded	O
+4	O
+-	O
+5	O
+,	O
+only	O
+27	O
+%	O
+had	O
+a	O
+fair	O
+out	O
+come	O
+.	O
+
+Activity	O
+of	O
+acid	B-GENE
+hydrolases	I-GENE
+of	O
+peripheral	O
+blood	O
+leukocytes	O
+in	O
+focal	O
+and	O
+segmental	O
+pneumonia	O
+in	O
+children	O
+
+Comparative	O
+studies	O
+of	O
+the	O
+antithrombin	B-GENE
+III	I-GENE
+level	O
+and	O
+plasminogen	B-GENE
+activator	I-GENE
+activity	O
+in	O
+patients	O
+with	O
+thrombophlebitis	O
+
+Relations	O
+between	O
+cellular	O
+electrical	O
+activity	O
+and	O
+cardiac	O
+mechanical	O
+activity	O
+in	O
+man	O
+,	O
+the	O
+dog	O
+and	O
+the	O
+rabbit	O
+
+Treatment	O
+of	O
+Paget	O
+'	O
+s	O
+disease	O
+.	O
+
+Improvement	O
+of	O
+the	O
+CRT	O
+display	O
+of	O
+an	O
+averager	O
+.	O
+
+Is	O
+desensitization	O
+'	O
+for	O
+ragweed	O
+hay	O
+fever	O
+immunologically	O
+specific	O
+?	O
+
+Renal	O
+excretion	O
+of	O
+sulphadimidine	O
+in	O
+normal	O
+and	O
+uraemic	O
+subjects	O
+.	O
+
+Experiences	O
+with	O
+the	O
+clinical	O
+and	O
+experimental	O
+use	O
+of	O
+Urat	O
+-	O
+I	O
+lithotriptor	O
+.	O
+
+Formation	O
+of	O
+hyphae	O
+and	O
+chlamydospores	O
+by	O
+Cryptococcus	O
+laurentii	O
+.	O
+
+Evaluation	O
+of	O
+thyroid	O
+function	O
+.	O
+
+The	O
+effect	O
+of	O
+a	O
+tissue	O
+emulsion	O
+,	O
+vitamin	O
+A	O
+and	O
+nonspecific	O
+gamma	B-GENE
+-	I-GENE
+globulin	I-GENE
+on	O
+the	O
+blood	O
+clearance	O
+in	O
+rabbits	O
+
+HL	B-GENE
+-	I-GENE
+A	I-GENE
+antibodies	I-GENE
+in	O
+polytransfused	O
+patients	O
+
+Demonstration	O
+of	O
+fine	O
+structure	O
+of	O
+the	O
+guinea	O
+pig	O
+organ	O
+of	O
+Corti	O
+after	O
+electron	O
+microscopic	O
+silver	O
+staining	O
+
+Histamine	O
+metabolism	O
+in	O
+hemorrhagic	O
+-	O
+hypotensive	O
+shock	O
+
+Relaxation	O
+of	O
+catch	O
+in	O
+a	O
+molluscan	O
+smooth	O
+muscle	O
+.	O
+
+Studies	O
+on	O
+alcoholic	O
+liver	O
+injury	O
+.	O
+
+Hypothalamic	O
+control	O
+of	O
+coronary	O
+circulation	O
+in	O
+the	O
+dog	O
+.	O
+
+Evidence	O
+for	O
+two	O
+distinctive	O
+clinical	O
+,	O
+epidemiological	O
+,	O
+and	O
+immunological	O
+types	O
+of	O
+infection	O
+.	O
+
+Ultraviolet	O
+light	O
+-	O
+induced	O
+kinin	B-GENE
+formation	O
+in	O
+human	O
+skin	O
+.	O
+
+Poliomyelitis	O
+from	O
+a	O
+vaccine	O
+.	O
+
+To	O
+the	O
+problem	O
+of	O
+the	O
+stimulation	O
+of	O
+the	O
+growth	O
+of	O
+transplantable	O
+tumors	O
+of	O
+animals	O
+previously	O
+treated	O
+with	O
+antineoplastic	O
+antibiotics	O
+
+Assessment	O
+of	O
+nutrient	O
+media	O
+in	O
+the	O
+diagnosis	O
+of	O
+diptheria	O
+
+Aluminium	O
+resin	O
+for	O
+the	O
+treatment	O
+of	O
+the	O
+hyperkalamia	O
+of	O
+renal	O
+failure	O
+.	O
+
+Value	O
+of	O
+the	O
+EMG	O
+in	O
+the	O
+diagnosis	O
+of	O
+a	O
+cardiomyopathy	O
+associated	O
+with	O
+a	O
+myotonic	O
+myopathy	O
+.	O
+
+D	O
+.	O
+
+Prevention	O
+of	O
+maternal	O
+Rh	O
+sensitization	O
+:	O
+anti	B-GENE
+-	I-GENE
+Rh	I-GENE
+immune	I-GENE
+globulin	I-GENE
+.	O
+
+Serotonin	O
+levels	O
+in	O
+infant	O
+hypothyroidism	O
+.	O
+
+Cerebrospinal	O
+fluid	O
+transferrin	B-GENE
+II	I-GENE
+studies	O
+in	O
+ischemic	O
+disorders	O
+of	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+High	O
+dosages	O
+of	O
+D	O
+-	O
+penicillamine	O
+in	O
+pulmonary	O
+fibroses	O
+
+Inverse	O
+relation	O
+between	O
+serum	O
+IgG	B-GENE
+concentration	O
+and	O
+glucose	O
+and	O
+xylose	O
+absorption	O
+in	O
+Zambian	O
+African	O
+adults	O
+.	O
+
+Disorders	O
+of	O
+platelet	O
+function	O
+in	O
+chronic	O
+myeloid	O
+leukemias	O
+
+The	O
+effect	O
+of	O
+anticonvulsants	O
+on	O
+sodium	B-GENE
+-	I-GENE
+potassium	I-GENE
+-	I-GENE
+activated	I-GENE
+ATPase	I-GENE
+,	O
+sodium	O
+,	O
+and	O
+potassim	O
+in	O
+cortex	O
+.	O
+
+Effect	O
+of	O
+immune	O
+lymphocytes	O
+and	O
+of	O
+rabbit	B-GENE
+-	I-GENE
+anti	I-GENE
+-	I-GENE
+lymphocyte	I-GENE
+globulin	I-GENE
+(	O
+RAMLG	B-GENE
+)	O
+on	O
+infected	O
+macrophages	O
+exposed	O
+to	O
+increased	O
+incubation	O
+temperature	O
+in	O
+vitro	O
+.	O
+
+Lactation	O
+of	O
+baboons	O
+fed	O
+a	O
+low	O
+protein	O
+maintenance	O
+diet	O
+.	O
+
+A	O
+medical	O
+-	O
+geographical	O
+review	O
+
+Age	O
+and	O
+sex	O
+structure	O
+of	O
+the	O
+natural	O
+population	O
+of	O
+Ornithodoros	O
+tatarovski	O
+Ol	O
+.	O
+
+Vitamin	O
+D3	O
+and	O
+calcium	O
+absorption	O
+in	O
+the	O
+chick	O
+.	O
+
+The	O
+incidence	O
+of	O
+tumours	O
+in	O
+young	O
+chickens	O
+.	O
+
+Laboratory	O
+aspects	O
+with	O
+particular	O
+reference	O
+to	O
+chemotherapy	O
+and	O
+control	O
+.	O
+
+Their	O
+effect	O
+on	O
+the	O
+guinea	O
+pig	O
+vas	O
+deferens	O
+.	O
+
+Androgens	O
+and	O
+growth	O
+.	O
+
+Therapeutic	O
+action	O
+of	O
+a	O
+new	O
+antibiotic	O
+-	O
+corticoid	O
+association	O
+used	O
+for	O
+instillations	O
+in	O
+otology	O
+
+Clinico	O
+-	O
+physiological	O
+experiment	O
+
+Enzyme	O
+histochemical	O
+findings	O
+in	O
+the	O
+ultimobranchial	O
+body	O
+of	O
+the	O
+horse	O
+
+Familial	O
+glutathione	B-GENE
+reductase	I-GENE
+deficiency	O
+and	O
+disorder	O
+of	O
+glutathione	O
+synthesis	O
+in	O
+the	O
+erythrocyte	O
+
+Studies	O
+on	O
+swine	O
+enteroviruses	O
+.	O
+
+Serodiagnosis	O
+of	O
+ectromelia	O
+in	O
+laboratory	O
+mice	O
+
+Ultrasound	O
+effect	O
+on	O
+the	O
+cytochrome	B-GENE
+oxidase	I-GENE
+activity	O
+
+Genesis	O
+of	O
+foam	O
+cells	O
+:	O
+study	O
+in	O
+rats	O
+after	O
+administration	O
+of	O
+Cloforex	O
+.	O
+
+Conditions	O
+influencing	O
+inhibitors	O
+of	O
+the	O
+colony	B-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+CSF	B-GENE
+)	O
+.	O
+
+Absence	O
+of	O
+action	O
+potentials	O
+in	O
+frog	O
+slow	O
+muscle	O
+fibres	O
+paralysed	O
+by	O
+botulinum	B-GENE
+toxin	I-GENE
+.	O
+
+An	O
+automated	O
+method	O
+for	O
+the	O
+quantitative	O
+analysis	O
+of	O
+the	O
+polyamines	O
+putrescine	O
+,	O
+spermidine	O
+and	O
+spermine	O
+in	O
+cerebrospinal	O
+fluid	O
+(	O
+CSF	O
+)	O
+was	O
+used	O
+to	O
+analyze	O
+CSF	O
+samples	O
+from	O
+37	O
+patients	O
+with	O
+central	O
+nervous	O
+system	O
+(	O
+CNS	O
+)	O
+tumors	O
+and	O
+from	O
+13	O
+patients	O
+without	O
+tumors	O
+.	O
+
+Disulfiram	O
+and	O
+the	O
+drug	O
+-	O
+induced	O
+effects	O
+on	O
+motility	O
+.	O
+
+Particles	O
+resembling	O
+microbodies	O
+in	O
+normal	O
+and	O
+neoplastic	O
+perianal	O
+glands	O
+of	O
+dogs	O
+.	O
+
+Natural	O
+and	O
+induced	O
+malarias	O
+in	O
+western	O
+hemisphere	O
+monkeys	O
+.	O
+
+Intracranial	O
+arachnoid	O
+cyst	O
+of	O
+the	O
+middle	O
+fossa	O
+demonstrated	O
+by	O
+positive	O
+99mTc	O
+brainscintigraphy	O
+.	O
+
+Effects	O
+of	O
+estrogen	O
+and	O
+glucocorticoids	O
+on	O
+the	O
+adrenal	O
+development	O
+of	O
+the	O
+fetus	O
+.	O
+
+Copper	O
+and	O
+ceruloplasmin	B-GENE
+content	O
+in	O
+pregnant	O
+women	O
+and	O
+in	O
+women	O
+with	O
+certain	O
+gynecological	O
+diseases	O
+
+Effect	O
+of	O
+noise	O
+on	O
+CO	O
+-	O
+induced	O
+increases	O
+of	O
+LAP	B-GENE
+and	O
+GPT	B-GENE
+activity	O
+in	O
+the	O
+plasma	O
+of	O
+rats	O
+
+Kinetics	O
+of	O
+calcium	O
+metabolism	O
+.	O
+
+On	O
+the	O
+transport	O
+of	O
+mucus	O
+and	O
+its	O
+rheologic	O
+simulants	O
+in	O
+ciliated	O
+systems	O
+.	O
+
+A	O
+hydrodynamic	O
+description	O
+of	O
+the	O
+osmotic	O
+reflection	O
+coefficient	O
+with	O
+application	O
+to	O
+the	O
+pore	O
+theory	O
+of	O
+transcapillary	O
+exchange	O
+.	O
+
+Pathology	O
+of	O
+neuritis	O
+caudae	O
+equinae	O
+in	O
+the	O
+horse	O
+
+Abnormal	O
+characteristics	O
+and	O
+verticillation	O
+in	O
+Platynothrus	O
+peltifer	O
+
+Selected	O
+topics	O
+in	O
+laboratory	O
+animal	O
+medicine	O
+.	O
+
+On	O
+parents	O
+
+From	O
+the	O
+Icelandic	O
+Red	O
+Cross	O
+activities	O
+
+Effects	O
+of	O
+alcoholism	O
+on	O
+the	O
+family	O
+
+Treatment	O
+and	O
+care	O
+of	O
+adult	O
+diabetes	O
+mellitus	O
+without	O
+coma	O
+
+Junctions	O
+between	O
+cells	O
+of	O
+the	O
+human	O
+enamel	O
+organ	O
+.	O
+
+Electrocardiograms	O
+of	O
+the	O
+month	O
+.	O
+
+Composites	O
+as	O
+restoration	O
+materials	O
+
+Hodgkin	O
+'	O
+s	O
+disease	O
+.	O
+
+Value	O
+of	O
+Normotest	O
+and	O
+antithrombin	B-GENE
+3	I-GENE
+in	O
+the	O
+assessment	O
+of	O
+liver	O
+function	O
+.	O
+
+Glutathione	B-GENE
+peroxidase	I-GENE
+in	O
+human	O
+red	O
+cells	O
+in	O
+health	O
+and	O
+disease	O
+.	O
+
+Histopathologic	O
+response	O
+of	O
+gingival	O
+tissues	O
+to	O
+hemodent	O
+and	O
+aluminum	O
+chloride	O
+solutions	O
+as	O
+tissue	O
+displacement	O
+materials	O
+.	O
+
+Changes	O
+following	O
+periodontal	O
+surgery	O
+.	O
+
+Intracellular	O
+pH	O
+,	O
+H	O
+ion	O
+flux	O
+and	O
+H	O
+ion	O
+permeability	O
+coefficient	O
+in	O
+bullfrog	O
+toe	O
+muscle	O
+.	O
+
+Directives	O
+concerning	O
+medical	O
+care	O
+
+Proceedings	O
+:	O
+Reversible	O
+complete	O
+heart	O
+block	O
+following	O
+surgery	O
+of	O
+congenital	O
+heart	O
+defects	O
+
+Method	O
+of	O
+synthesis	O
+of	O
+the	O
+rheumatoid	B-GENE
+factor	I-GENE
+in	O
+clinico	O
+-	O
+immunological	O
+studies	O
+
+Variations	O
+of	O
+the	O
+timing	O
+of	O
+deflections	O
+in	O
+the	O
+His	O
+bundle	O
+recordings	O
+.	O
+
+Extracellular	O
+fibril	O
+formation	O
+by	O
+neuroglial	O
+cells	O
+at	O
+the	O
+vitreoretinal	O
+junction	O
+of	O
+the	O
+human	O
+eye	O
+.	O
+
+Blood	O
+platelets	O
+,	O
+coagulation	O
+factors	O
+and	O
+morphologic	O
+organ	O
+changes	O
+following	O
+scalding	O
+shock	O
+in	O
+rhesus	O
+monkeys	O
+
+Cell	O
+viability	O
+and	O
+lysosomal	B-GENE
+enzymes	I-GENE
+
+State	O
+-	O
+approved	O
+schools	O
+of	O
+nursing	O
+-	O
+-	O
+R	O
+.	O
+N	O
+.	O
+,	O
+1972	O
+.	O
+
+Further	O
+investigation	O
+on	O
+the	O
+chemotactic	O
+influence	O
+of	O
+thymic	B-GENE
+hormone	I-GENE
+on	O
+lymphocytes	O
+
+1	O
+,	O
+3	O
+-	O
+bis	O
+(	O
+2	O
+-	O
+chloroethyl	O
+)	O
+-	O
+1	O
+-	O
+nitrosourea	O
+(	O
+bcnu	O
+)	O
+and	O
+other	O
+nitrosoureas	O
+in	O
+cancer	O
+treatment	O
+:	O
+a	O
+review	O
+.	O
+
+Pneumothorax	O
+following	O
+lung	O
+abscess	O
+in	O
+the	O
+renal	O
+transplant	O
+patient	O
+.	O
+
+Taxonomically	O
+significant	O
+colour	O
+changes	O
+in	O
+Brevibacterium	O
+linens	O
+probably	O
+associated	O
+with	O
+a	O
+carotenoid	O
+-	O
+like	O
+pigment	O
+.	O
+
+Temporal	O
+relationships	O
+and	O
+the	O
+development	O
+phase	O
+affected	O
+.	O
+
+A	O
+short	O
+history	O
+of	O
+dermatology	O
+in	O
+Lagos	O
+,	O
+Nigeria	O
+.	O
+
+Local	O
+graft	O
+irradiation	O
+as	O
+an	O
+adjunct	O
+to	O
+pharmacologic	O
+immunosuppression	O
+.	O
+
+Letter	O
+:	O
+Salmonella	O
+detection	O
+
+Role	O
+of	O
+biocenosis	O
+in	O
+the	O
+manifestation	O
+of	O
+Shigella	O
+virulence	O
+
+The	O
+effect	O
+of	O
+antilymphocyte	O
+sera	O
+on	O
+formation	O
+of	O
+transplantation	O
+and	O
+anti	O
+-	O
+infection	O
+immunity	O
+in	O
+mice	O
+
+Cortical	O
+afferents	O
+to	O
+the	O
+entorhinal	O
+cortex	O
+of	O
+the	O
+Rhesus	O
+monkey	O
+.	O
+
+Mechanism	O
+of	O
+immunogenesis	O
+in	O
+vaccination	O
+with	O
+streptomycin	O
+-	O
+dependent	O
+mutants	O
+of	O
+salmonellae	O
+and	O
+shigellae	O
+.	O
+
+Resistance	O
+pattern	O
+of	O
+Mycobacterium	O
+tuberculosis	O
+(	O
+H	O
+37	O
+Rv	O
+)	O
+to	O
+a	O
+new	O
+antibiotic	O
+,	O
+lividomycin	O
+
+Pulmonary	O
+arterial	O
+pressure	O
+and	O
+structure	O
+in	O
+the	O
+patas	O
+monkey	O
+after	O
+prolonged	O
+administration	O
+of	O
+aminorex	O
+fumarate	O
+.	O
+
+Effect	O
+of	O
+triftazin	O
+and	O
+aminazin	O
+on	O
+hippocampal	O
+bioelectric	O
+activity	O
+
+Sex	O
+ratio	O
+at	O
+birth	O
+.	O
+
+Pathological	O
+processes	O
+in	O
+the	O
+cervix	O
+uteri	O
+
+General	O
+formulae	O
+for	O
+estimating	O
+heritability	O
+in	O
+a	O
+population	O
+with	O
+related	O
+parents	O
+.	O
+
+Measurement	O
+of	O
+open	O
+-	O
+loop	O
+responses	O
+to	O
+electrical	O
+stimulation	O
+in	O
+olfactory	O
+bulb	O
+of	O
+cat	O
+.	O
+
+Glucose	O
+disappearance	O
+rate	O
+and	O
+changes	O
+in	O
+plasma	O
+nutrients	O
+after	O
+intravenouly	O
+injected	O
+glucose	O
+in	O
+normoglycaemic	O
+and	O
+hypoglycaemic	O
+underweight	O
+newborns	O
+.	O
+
+Normal	O
+values	O
+for	O
+the	O
+peripheral	O
+blood	O
+and	O
+bone	O
+marrow	O
+of	O
+the	O
+grey	O
+(	O
+Armenian	O
+)	O
+hamster	O
+
+The	O
+relationship	O
+of	O
+human	O
+umbilical	O
+arterial	O
+and	O
+venous	O
+plasma	O
+levels	O
+of	O
+corticosteroids	O
+to	O
+gestational	O
+age	O
+.	O
+
+Antibiotic	O
+effect	O
+of	O
+the	O
+mud	O
+from	O
+heviz	O
+
+Sulfuric	O
+acid	O
+concentration	O
+in	O
+the	O
+catalyzed	O
+breathalyzer	O
+ampules	O
+.	O
+
+Role	O
+of	O
+histoclinical	O
+studies	O
+in	O
+the	O
+prophylaxis	O
+of	O
+spontaneous	O
+abortions	O
+
+Range	O
+behavior	O
+of	O
+Hereford	O
+,	O
+Hereford	O
+x	O
+Holstein	O
+and	O
+Holstein	O
+non	O
+-	O
+lactating	O
+heifers	O
+.	O
+
+Chemical	O
+constituents	O
+of	O
+the	O
+gentianaceae	O
+V	O
+:	O
+tetraoxygenated	O
+xanthones	O
+of	O
+Swertia	O
+chirata	O
+Buch	O
+.	O
+-	O
+Ham	O
+.	O
+
+Microdetermination	O
+of	O
+adrenocortical	O
+steroids	O
+by	O
+double	O
+isotope	O
+method	O
+.	O
+
+Compensative	O
+justice	O
+and	O
+moral	O
+investment	O
+among	O
+Japanese	O
+,	O
+Chinese	O
+,	O
+and	O
+Koreans	O
+.	O
+
+Effects	O
+of	O
+cortisone	O
+,	O
+starvation	O
+,	O
+and	O
+rickets	O
+on	O
+oxidative	O
+enzyme	O
+activities	O
+of	O
+epiphyseal	O
+cartilage	O
+from	O
+rats	O
+.	O
+
+Metal	O
+coordination	O
+compounds	O
+of	O
+thiabendazole	O
+.	O
+
+Estimation	O
+of	O
+renin	B-GENE
+secretion	O
+rate	O
+and	O
+renal	O
+plasma	O
+flow	O
+from	O
+peripheral	O
+and	O
+renal	B-GENE
+vein	I-GENE
+renin	I-GENE
+levels	O
+.	O
+
+Choice	O
+of	O
+vessel	O
+.	O
+
+Suppression	O
+of	O
+food	O
+intake	O
+in	O
+the	O
+rat	O
+by	O
+tung	O
+oil	O
+.	O
+
+Studies	O
+of	O
+lipoprotein	B-GENE
+-	I-GENE
+X	I-GENE
+(	O
+LP	B-GENE
+-	I-GENE
+X	I-GENE
+)	O
+and	O
+bile	O
+acids	O
+in	O
+familial	O
+LCAT	B-GENE
+deficiency	O
+.	O
+
+Pneumothorax	O
+complicated	O
+by	O
+chronic	O
+steroid	O
+treatment	O
+.	O
+
+Manifest	O
+anxiety	O
+of	O
+Vietnam	O
+returnees	O
+and	O
+undergraduates	O
+.	O
+
+Familial	O
+juvenile	O
+nephronophthisis	O
+
+Early	O
+heparin	O
+therapy	O
+in	O
+60	O
+children	O
+with	O
+acute	O
+meningococcemia	O
+.	O
+
+9	O
+,	O
+11	O
+-	O
+Seco	O
+steroids	O
+derived	O
+from	O
+estradiol	O
+3	O
+-	O
+methyl	O
+ether	O
+.	O
+
+Psychological	O
+examinations	O
+in	O
+patients	O
+with	O
+chronic	O
+kidney	O
+insufficiency	O
+
+Possibilities	O
+of	O
+needleless	O
+administration	O
+of	O
+various	O
+substances	O
+to	O
+animals	O
+
+Change	O
+in	O
+the	O
+makeup	O
+of	O
+the	O
+blood	O
+following	O
+a	O
+short	O
+-	O
+term	O
+local	O
+action	O
+of	O
+a	O
+permanent	O
+magnetic	O
+field	O
+on	O
+the	O
+human	O
+body	O
+
+Observations	O
+on	O
+the	O
+flight	O
+activities	O
+of	O
+Chrysops	O
+caecutiens	O
+L	O
+.	O
+
+Combination	O
+of	O
+3	O
+multiple	O
+primary	O
+malignant	O
+and	O
+benign	O
+tumors	O
+of	O
+the	O
+breasts	O
+and	O
+uterus	O
+
+Proceedings	O
+:	O
+Barrels	O
+and	O
+somatotopy	O
+in	O
+S	O
+I	O
+neocortex	O
+of	O
+the	O
+brush	O
+-	O
+tailed	O
+possum	O
+.	O
+
+Antivitamin	O
+K	O
+agents	O
+
+Canine	O
+reproduction	O
+:	O
+effects	O
+of	O
+a	O
+single	O
+injection	O
+of	O
+medroxyprogesterone	O
+acetate	O
+on	O
+the	O
+reproductive	O
+organs	O
+of	O
+the	O
+bitch	O
+.	O
+
+3	O
+.	O
+
+Hypoglycemic	O
+and	O
+antidiabetic	O
+properties	O
+
+Hematopoietic	O
+system	O
+in	O
+streptococcal	O
+allergy	O
+.	O
+
+Letter	O
+:	O
+Aryl	B-GENE
+hydrocarbon	I-GENE
+hydroxylase	I-GENE
+and	O
+smoking	O
+.	O
+
+Evaluation	O
+of	O
+1	O
+,	O
+10	O
+-	O
+phenanthroline	O
+as	O
+a	O
+reagent	O
+for	O
+sialic	O
+acid	O
+determinations	O
+.	O
+
+Delta	O
+-	O
+aminolevulinic	O
+acid	O
+in	O
+physiological	O
+conditions	O
+and	O
+some	O
+diseases	O
+in	O
+children	O
+
+Nonteratogenicity	O
+in	O
+rats	O
+of	O
+blighted	O
+potatoes	O
+and	O
+compounds	O
+contained	O
+in	O
+them	O
+.	O
+
+Isolation	O
+of	O
+tha	O
+avian	O
+reticuloendothelial	O
+virus	O
+(	O
+strain	O
+T	O
+)	O
+.	O
+
+Observations	O
+on	O
+saccules	O
+of	O
+rats	O
+exposed	O
+to	O
+long	O
+-	O
+term	O
+hypergravity	O
+.	O
+
+The	O
+levels	O
+of	O
+galactosyltransferase	B-GENE
+activity	O
+in	O
+sera	O
+from	O
+normal	O
+children	O
+and	O
+patients	O
+with	O
+cystic	O
+fibrosis	O
+.	O
+
+Lack	O
+of	O
+effect	O
+of	O
+the	O
+appetite	O
+stimulant	O
+pizotifen	O
+(	O
+BC	O
+105	O
+)	O
+on	O
+the	O
+absorption	O
+of	O
+isonicotinylhydrazine	O
+.	O
+
+Relationship	O
+between	O
+gross	O
+lesions	O
+and	O
+Escherichia	O
+coli	O
+serotypes	O
+in	O
+chronic	O
+respiratory	O
+disease	O
+(	O
+CRD	O
+)	O
+of	O
+poultry	O
+.	O
+
+Immunelectrophoretic	O
+pattern	O
+of	O
+Wassermann	O
+reagin	O
+and	O
+comparison	O
+of	O
+the	O
+appearance	O
+time	O
+between	O
+RPCF	B-GENE
+and	O
+FTA	B-GENE
+antibodies	I-GENE
+
+Motile	O
+nocardoid	O
+Actinomycetales	O
+.	O
+
+Electrocardiographic	O
+QRS	O
+complexes	O
+and	O
+vectorcardiographic	O
+QRS	O
+loop	O
+
+Cardiac	O
+preservation	O
+.	O
+
+Labial	O
+bar	O
+.	O
+
+Yusuf	O
+Dawood	O
+Docrat	O
+L	O
+.	O
+R	O
+.	O
+C	O
+.	O
+P	O
+.	O
+
+Dr	O
+.	O
+
+The	O
+metabolism	O
+and	O
+pharmacology	O
+of	O
+5	O
+-	O
+fluorouracil	O
+.	O
+
+Spleen	O
+weight	O
+in	O
+rats	O
+during	O
+tumour	O
+growth	O
+and	O
+in	O
+homograft	O
+rejection	O
+.	O
+
+Isolation	O
+of	O
+Proteus	O
+vulgaris	O
+MC	O
+-	O
+63	O
+from	O
+carcinoma	O
+63	O
+and	O
+its	O
+antitumor	O
+effect	O
+on	O
+Crocker	O
+sarcoma	O
+180	O
+and	O
+Ehrlich	O
+carcinoma	O
+.	O
+
+Human	O
+synovial	O
+fluid	O
+:	O
+detection	O
+of	O
+a	O
+new	O
+component	O
+.	O
+
+Effects	O
+of	O
+temperature	O
+and	O
+moulting	O
+cycle	O
+on	O
+melanin	O
+synthesis	O
+in	O
+the	O
+newt	O
+,	O
+Triturus	O
+cristatus	O
+.	O
+
+LA	O
+-	O
+3848	O
+-	O
+MS	O
+.	O
+
+Immunochemical	O
+studies	O
+with	O
+filarial	O
+antigens	O
+.	O
+
+Morphological	O
+and	O
+functional	O
+alterations	O
+noted	O
+after	O
+baboon	O
+renal	O
+allotransplantation	O
+.	O
+
+Heterogeneity	O
+of	O
+human	B-GENE
+serum	I-GENE
+albumin	I-GENE
+.	O
+
+Analysis	O
+of	O
+corticosteroids	O
+.	O
+
+Plasma	B-GENE
+histaminase	I-GENE
+in	O
+patients	O
+of	O
+bronchial	O
+asthma	O
+and	O
+the	O
+effect	O
+of	O
+prednisolone	O
+administration	O
+on	O
+it	O
+.	O
+
+A	O
+comparative	O
+study	O
+of	O
+the	O
+cortical	O
+end	O
+of	O
+the	O
+auditory	O
+analyzer	O
+during	O
+postnatal	O
+ontogenesis	O
+in	O
+lower	O
+monkeys	O
+and	O
+man	O
+
+Immunogenicity	O
+of	O
+various	O
+mycobacteria	O
+and	O
+the	O
+corresponding	O
+levels	O
+of	O
+cross	O
+-	O
+protection	O
+developed	O
+between	O
+species	O
+.	O
+
+Ten	O
+-	O
+year	O
+experience	O
+with	O
+one	O
+-	O
+stage	O
+proctocolectomy	O
+and	O
+anal	O
+ileostomy	O
+.	O
+
+Factors	O
+affecting	O
+the	O
+inhibition	O
+of	O
+phagocytosis	O
+by	O
+chlorpromazine	O
+.	O
+
+Photopic	O
+spectral	O
+sensitivity	O
+determined	O
+electroretinographically	O
+for	O
+the	O
+pigeon	O
+eye	O
+.	O
+
+Angiography	O
+of	O
+aneurysmal	O
+bone	O
+cyst	O
+.	O
+
+Cholinesterase	B-GENE
+
+Sodium	O
+restriction	O
+in	O
+cardiac	O
+failure	O
+.	O
+
+Clinical	O
+and	O
+angiographic	O
+examinations	O
+in	O
+occlusion	O
+disease	O
+of	O
+the	O
+great	O
+intestinal	O
+arteries	O
+
+Serum	O
+lipid	O
+changes	O
+during	O
+pregnancy	O
+due	O
+to	O
+oral	O
+calcium	O
+administration	O
+
+Successful	O
+treatment	O
+of	O
+candidiasis	O
+with	O
+transfer	B-GENE
+factor	I-GENE
+.	O
+
+Clinicopathologic	O
+studies	O
+in	O
+feminizing	O
+tumors	O
+of	O
+the	O
+ovary	O
+.	O
+
+On	O
+the	O
+constituents	O
+of	O
+Dryopteris	O
+polylepis	O
+
+Relation	O
+between	O
+mixing	O
+ratio	O
+of	O
+raw	O
+materials	O
+and	O
+composition	O
+of	O
+products	O
+in	O
+the	O
+synthesis	O
+of	O
+aluminosilicates	O
+
+Influence	O
+of	O
+diet	O
+on	O
+urinary	O
+VMA	O
+excretion	O
+.	O
+
+Oscilloscope	O
+triggering	O
+circuit	O
+for	O
+recording	O
+long	O
+transients	O
+at	O
+fast	O
+sweep	O
+speeds	O
+.	O
+
+Derivatives	O
+of	O
+boswellic	O
+acids	O
+.	O
+
+The	O
+status	O
+of	O
+education	O
+and	O
+training	O
+programs	O
+in	O
+speech	O
+pathology	O
+and	O
+audiology	O
+-	O
+-	O
+1971	O
+-	O
+72	O
+.	O
+
+Coronary	O
+arteries	O
+-	O
+-	O
+old	O
+and	O
+new	O
+.	O
+
+Antiviral	O
+agents	O
+.	O
+
+Separation	O
+of	O
+ninhydrin	O
+-	O
+positive	O
+compounds	O
+in	O
+urine	O
+by	O
+the	O
+combined	O
+methods	O
+of	O
+medium	O
+-	O
+tension	O
+intophoresis	O
+and	O
+partition	O
+chromatography	O
+
+Conservative	O
+treatment	O
+of	O
+central	O
+nervous	O
+system	O
+injuries	O
+
+Spasmus	O
+nutans	O
+:	O
+a	O
+syndrome	O
+of	O
+auto	O
+-	O
+arousal	O
+.	O
+
+6	O
+.	O
+
+1st	O
+data	O
+on	O
+the	O
+immunosuppressive	O
+therapy	O
+of	O
+scleroderma	O
+
+Slowed	O
+lysosomal	B-GENE
+enzyme	I-GENE
+release	O
+and	O
+its	O
+normalization	O
+by	O
+drugs	O
+in	O
+adjuvant	O
+-	O
+induced	O
+polyarthritis	O
+.	O
+
+Treatment	O
+of	O
+ovarian	O
+neoplasms	O
+
+Experimental	O
+pancreatitis	O
+in	O
+pigs	O
+.	O
+
+Bacterial	O
+metabolism	O
+of	O
+4	O
+-	O
+chlorophenoxyacetate	O
+.	O
+
+I	O
+.	O
+
+Surgical	O
+treatment	O
+of	O
+pathologic	O
+scars	O
+of	O
+myocardial	O
+infarct	O
+
+The	O
+interaction	O
+of	O
+caffeine	O
+,	O
+theophylline	O
+and	O
+theobromine	O
+with	O
+monoamine	B-GENE
+oxidase	I-GENE
+inhibitors	O
+.	O
+
+Effect	O
+of	O
+phenformin	O
+on	O
+gluconeogenesis	O
+in	O
+perfused	O
+rat	O
+liver	O
+.	O
+
+New	O
+alkaloids	O
+from	O
+bark	O
+of	O
+Erythrophleum	O
+ivorense	O
+.	O
+
+Radiosensitive	O
+nature	O
+of	O
+paravascular	O
+infiltrate	O
+-	O
+producing	O
+potential	O
+of	O
+parental	O
+spleen	O
+cells	O
+.	O
+
+Sinusoidal	O
+oscillations	O
+of	O
+a	O
+gas	O
+dilution	O
+indicator	O
+
+The	O
+value	O
+of	O
+different	O
+sources	O
+of	O
+nitrogen	O
+in	O
+diets	O
+for	O
+the	O
+early	O
+-	O
+weaned	O
+calf	O
+.	O
+
+1	O
+.	O
+
+Abdominal	O
+tumors	O
+in	O
+childhood	O
+.	O
+
+Studies	O
+on	O
+the	O
+hereditary	O
+nature	O
+of	O
+sole	O
+prints	O
+-	O
+-	O
+with	O
+special	O
+reference	O
+to	O
+interdigital	O
+and	O
+triradii	O
+
+The	O
+problem	O
+of	O
+disablement	O
+due	O
+to	O
+pulmonary	O
+tuberculosis	O
+,	O
+on	O
+the	O
+basis	O
+of	O
+an	O
+analysis	O
+of	O
+the	O
+history	O
+of	O
+395	O
+cases	O
+as	O
+observed	O
+in	O
+Gdansk	O
+in	O
+the	O
+years	O
+1946	O
+-	O
+1965	O
+
+Cleidocranial	O
+dysostosis	O
+
+Proposals	O
+on	O
+authorization	O
+;	O
+by	O
+a	O
+group	O
+of	O
+nurses	O
+from	O
+psychiatric	O
+hospitals	O
+
+Successive	O
+abdominal	O
+scintillation	O
+with	O
+131	O
+-	O
+I	O
+-	O
+tagged	O
+BSP	O
+-	O
+-	O
+description	O
+of	O
+the	O
+thyroid	O
+gland	O
+,	O
+kidney	O
+and	O
+spleen	O
+(	O
+comparison	O
+with	O
+131	O
+-	O
+I	O
+-	O
+RB	O
+)	O
+
+Pneumonia	O
+in	O
+children	O
+
+Osteosarcoma	O
+caused	O
+by	O
+3	O
+,	O
+4	O
+-	O
+benzopyrene	O
+
+Relapse	O
+of	O
+leukemia	O
+after	O
+prolonged	O
+remission	O
+.	O
+
+Influence	O
+of	O
+cigarette	O
+smoking	O
+on	O
+some	O
+blood	O
+coagulation	O
+tests	O
+.	O
+
+Second	O
+report	O
+of	O
+the	O
+Norwegian	O
+Cancer	O
+Society	O
+.	O
+
+SAM	O
+-	O
+TR	O
+-	O
+68	O
+-	O
+54	O
+.	O
+
+A	O
+brief	O
+discussion	O
+of	O
+color	O
+deficiencies	O
+.	O
+
+BIM	O
+130	O
+.	O
+
+Problems	O
+in	O
+the	O
+determination	O
+of	O
+the	O
+antigenic	O
+content	O
+of	O
+influenza	O
+vaccines	O
+.	O
+
+Aedes	O
+aegypti	O
+(	O
+L	O
+.	O
+)	O
+and	O
+Aedes	O
+albopictus	O
+(	O
+Skuse	O
+)	O
+in	O
+Singapore	O
+City	O
+.	O
+
+Homograft	O
+response	O
+and	O
+hemagglutinin	B-GENE
+production	O
+by	O
+sensitized	O
+thymectomized	O
+irradiated	O
+adult	O
+mice	O
+.	O
+
+Comparative	O
+study	O
+on	O
+acute	O
+oral	O
+overload	O
+using	O
+tolbutamide	O
+and	O
+tolazamide	O
+in	O
+normal	O
+and	O
+diabetic	O
+subjects	O
+.	O
+
+Mycotoxins	O
+in	O
+feeds	O
+and	O
+foods	O
+.	O
+
+Spinal	O
+cord	O
+representation	O
+of	O
+the	O
+micturition	O
+reflex	O
+.	O
+
+Biological	O
+action	O
+and	O
+kinetics	O
+of	O
+the	O
+elimination	O
+of	O
+tritium	O
+oxide	O
+in	O
+dogs	O
+
+Auto	O
+-	O
+and	O
+isotopy	O
+of	O
+the	O
+conjunctiva	O
+
+IX	O
+.	O
+
+Pitfalls	O
+in	O
+the	O
+use	O
+of	O
+chromosome	O
+aberration	O
+analysis	O
+for	O
+biological	O
+radiation	O
+dosimetry	O
+.	O
+
+Renin	B-GENE
+secretion	O
+in	O
+essential	O
+and	O
+accelerated	O
+hypertension	O
+.	O
+
+The	O
+need	O
+for	O
+including	O
+forensic	O
+medical	O
+expertise	O
+in	O
+the	O
+list	O
+of	O
+urgent	O
+criminal	O
+investigative	O
+actions	O
+
+Histopathology	O
+and	O
+pathogenesis	O
+of	O
+exanthematous	O
+viroses	O
+
+CNS	O
+effects	O
+of	O
+local	O
+anesthetics	O
+only	O
+partially	O
+dependent	O
+on	O
+biogenic	O
+amine	O
+mechanisms	O
+.	O
+
+Diethylene	O
+benzene	O
+
+The	O
+effects	O
+of	O
+taloximine	O
+and	O
+aminophylline	O
+on	O
+isolated	O
+human	O
+smooth	O
+muscle	O
+.	O
+
+The	O
+exploratory	O
+behaviour	O
+in	O
+normal	O
+and	O
+aggressive	O
+mice	O
+.	O
+
+Genitography	O
+in	O
+intersexual	O
+states	O
+.	O
+
+The	O
+role	O
+of	O
+ascorbic	O
+acid	O
+in	O
+the	O
+prevention	O
+of	O
+bladder	O
+tumor	O
+formation	O
+.	O
+
+The	O
+"	O
+28	O
+percent	O
+"	O
+Venturi	O
+mask	O
+in	O
+obstructive	O
+airway	O
+disease	O
+.	O
+
+3	O
+'	O
+-	O
+Methyl	O
+,	O
+8	O
+-	O
+methyl	O
+,	O
+and	O
+8	O
+-	O
+phenyl	O
+derivatives	O
+of	O
+5	O
+,	O
+9	O
+-	O
+dimethyl	O
+-	O
+6	O
+,	O
+7	O
+-	O
+benzomorphans	O
+.	O
+
+Antidromic	O
+invasion	O
+of	O
+impulses	O
+and	O
+recurrent	O
+collateral	O
+inhibition	O
+in	O
+pyramidal	O
+tract	O
+neurones	O
+.	O
+
+Lipid	O
+concentration	O
+and	O
+lipase	B-GENE
+activity	O
+in	O
+the	O
+epiphysis	O
+of	O
+adrenalectomized	O
+rats	O
+consuming	O
+food	O
+with	O
+different	O
+sodium	O
+content	O
+
+Behavior	O
+of	O
+aspartate	B-GENE
+aminotransferase	I-GENE
+(	O
+EC	B-GENE
+2	I-GENE
+.	I-GENE
+6	I-GENE
+.	I-GENE
+1	I-GENE
+.	I-GENE
+1	I-GENE
+)	O
+and	O
+alanine	B-GENE
+aminotransferase	I-GENE
+(	O
+EC	B-GENE
+2	I-GENE
+.	I-GENE
+6	I-GENE
+.	I-GENE
+1	I-GENE
+.	I-GENE
+2	I-GENE
+)	O
+in	O
+rat	O
+serum	O
+during	O
+the	O
+course	O
+of	O
+acute	O
+radiation	O
+syndrome	O
+following	O
+whole	O
+body	O
+X	O
+-	O
+irradiation	O
+
+Diminished	O
+forearm	O
+arteriolar	O
+dilator	O
+capacity	O
+produced	O
+by	O
+mineralocorticoid	O
+-	O
+induced	O
+salt	O
+retention	O
+in	O
+man	O
+.	O
+
+Studies	O
+on	O
+the	O
+pathogenicity	O
+of	O
+ECHO	O
+9	O
+(	O
+HILL	O
+)	O
+virus	O
+and	O
+its	O
+mutants	O
+for	O
+suckling	O
+mice	O
+
+Counter	O
+-	O
+current	O
+heat	O
+exchange	O
+in	O
+the	O
+respiratory	O
+passages	O
+:	O
+effect	O
+on	O
+water	O
+and	O
+heat	O
+balance	O
+.	O
+
+Calibration	O
+and	O
+a	O
+correction	O
+of	O
+blood	O
+O2	O
+content	O
+measured	O
+by	O
+Po2	O
+and	O
+CO	O
+saturation	O
+.	O
+
+Mae	O
+West	O
+and	O
+the	O
+doctor	O
+shortage	O
+.	O
+
+Elimination	O
+of	O
+gamma	O
+-	O
+irradiation	O
+induced	O
+oxidation	O
+in	O
+aqueous	O
+drug	O
+preparations	O
+
+Teratogenic	O
+effects	O
+of	O
+actinomycin	O
+D	O
+in	O
+rats	O
+
+The	O
+plasma	B-GENE
+growth	I-GENE
+hormone	I-GENE
+concentration	O
+of	O
+the	O
+foetal	O
+lamb	O
+.	O
+
+Bimodal	O
+cochlear	O
+response	O
+curves	O
+in	O
+rodents	O
+.	O
+
+A	O
+new	O
+hemagglutination	O
+test	O
+for	O
+the	O
+on	O
+-	O
+slide	O
+assay	O
+of	O
+rheumatoid	B-GENE
+factor	I-GENE
+
+The	O
+biology	O
+of	O
+Hyostrongylus	O
+ruidus	O
+.	O
+
+Foreign	O
+profiles	O
+in	O
+air	O
+pollution	O
+control	O
+activities	O
+.	O
+
+Effects	O
+of	O
+chronic	O
+metaraminol	O
+treatment	O
+on	O
+the	O
+sympathetic	O
+activity	O
+of	O
+intact	O
+and	O
+adrenal	O
+demedullated	O
+rats	O
+kept	O
+in	O
+warm	O
+or	O
+cold	O
+environments	O
+.	O
+
+The	O
+association	O
+of	O
+clopamide	O
+and	O
+hydergine	O
+(	O
+Brinedine	O
+)	O
+in	O
+the	O
+treatment	O
+of	O
+the	O
+vasculo	O
+-	O
+renal	O
+syndromes	O
+of	O
+pregnancy	O
+
+Leukemia	O
+in	O
+twins	O
+:	O
+world	O
+-	O
+wide	O
+review	O
+of	O
+clinical	O
+cases	O
+.	O
+
+Preliminary	O
+report	O
+.	O
+
+Gastrointestinal	O
+manifestations	O
+of	O
+systemic	O
+sclerosis	O
+
+Total	O
+body	O
+water	O
+,	O
+rhodanide	O
+space	O
+and	O
+I	B-GENE
+-	I-GENE
+131	I-GENE
+-	I-GENE
+albumin	I-GENE
+space	O
+under	O
+the	O
+acute	O
+effect	O
+of	O
+furosemide	O
+
+V	O
+.	O
+
+18F	O
+and	O
+85Sr	O
+scintimetry	O
+in	O
+the	O
+study	O
+of	O
+primary	O
+arthropathies	O
+.	O
+
+Health	O
+:	O
+an	O
+integrative	O
+reticulum	O
+.	O
+
+Sensitive	O
+fluorometric	O
+method	O
+of	O
+determining	O
+SH	O
+-	O
+and	O
+S	O
+-	O
+S	O
+-	O
+groups	O
+when	O
+jointly	O
+present	O
+
+Behavioral	O
+and	O
+electrographic	O
+expression	O
+of	O
+natural	O
+sleep	O
+and	O
+wakefulness	O
+in	O
+reptiles	O
+
+Sensitivities	O
+of	O
+thromboplastins	B-GENE
+to	O
+factor	B-GENE
+VII	I-GENE
+deficiency	O
+.	O
+
+Central	O
+venous	O
+catheter	O
+used	O
+for	O
+recording	O
+intracardiac	O
+electrocardiogram	O
+.	O
+
+Two	O
+Lab	O
+8	O
+computer	O
+programmes	O
+for	O
+use	O
+in	O
+the	O
+study	O
+of	O
+the	O
+isometric	O
+and	O
+isotonic	O
+contractile	O
+characteristics	O
+of	O
+skeletal	O
+muscle	O
+.	O
+
+Open	O
+head	O
+-	O
+brain	O
+injuries	O
+
+The	O
+modification	O
+of	O
+P32	O
+uptake	O
+into	O
+the	O
+Jensen	O
+sarcoma	O
+in	O
+vitro	O
+by	O
+adding	O
+of	O
+peroxide	O
+to	O
+the	O
+nutritive	O
+medium	O
+
+Students	O
+,	O
+parents	O
+,	O
+teachers	O
+and	O
+hearing	O
+disorders	O
+
+Changing	O
+and	O
+predicting	O
+doses	O
+of	O
+Cs137	O
+irradiation	O
+
+Positive	O
+shifts	O
+of	O
+basal	O
+skin	O
+potentials	O
+during	O
+human	O
+sleep	O
+.	O
+
+Evaluating	O
+dietary	O
+department	O
+management	O
+.	O
+
+5	O
+-	O
+(	O
+Dimethylaminopropyl	O
+)	O
+-	O
+19	O
+,	O
+11	O
+-	O
+dihydro	O
+-	O
+5H	O
+-	O
+benzo	O
+[	O
+2	O
+,	O
+3	O
+]	O
+pyrido	O
+[	O
+6	O
+,	O
+7	O
+-	O
+b	O
+]	O
+azepine	O
+.	O
+
+Osteogenesis	O
+imperfecta	O
+
+Investigation	O
+on	O
+the	O
+exchange	O
+of	O
+Ca45	O
+in	O
+intact	O
+and	O
+burned	O
+rats	O
+by	O
+the	O
+kinetic	O
+analysis	O
+method	O
+
+Effect	O
+of	O
+thrombotic	O
+and	O
+antithrombotic	O
+drugs	O
+on	O
+the	O
+surface	O
+charge	O
+characteristics	O
+of	O
+canine	O
+blood	O
+vessels	O
+:	O
+in	O
+vivo	O
+and	O
+in	O
+vitro	O
+studies	O
+.	O
+
+Measurements	O
+of	O
+activity	O
+with	O
+the	O
+radioprotective	O
+chamber	O
+VA	O
+-	O
+K	O
+-	O
+254	O
+of	O
+the	O
+osimeter	O
+VA	O
+-	O
+J18	O
+
+3	O
+-	O
+(	O
+N	O
+-	O
+Alkyl	O
+-	O
+N	O
+-	O
+2	O
+-	O
+chloroethylaminomethyl	O
+)	O
+-	O
+5	O
+-	O
+or	O
+7	O
+-	O
+halogenobenzo	O
+[	O
+b	O
+]	O
+thiophen	O
+hydrochlorides	O
+.	O
+
+Determination	O
+of	O
+transaminases	O
+with	O
+an	O
+autoanalyzer	O
+
+Sterols	O
+in	O
+pollen	O
+.	O
+
+Dermoid	O
+cyst	O
+in	O
+a	O
+free	O
+skin	O
+flap	O
+as	O
+the	O
+complication	O
+after	O
+treatment	O
+of	O
+recurring	O
+hernia	O
+
+Histological	O
+observations	O
+on	O
+the	O
+decidua	O
+in	O
+the	O
+second	O
+half	O
+of	O
+pregnancy	O
+
+Endocardial	O
+fibro	O
+-	O
+elastosis	O
+,	O
+mitral	O
+incompetence	O
+,	O
+and	O
+coarctation	O
+of	O
+abdominal	O
+aorta	O
+.	O
+
+Studies	O
+on	O
+the	O
+method	O
+of	O
+size	O
+reduction	O
+of	O
+medicinal	O
+compounds	O
+.	O
+
+Children	O
+with	O
+defective	O
+vision	O
+
+Identification	O
+and	O
+estimation	O
+of	O
+monosaccharides	O
+and	O
+disaccharides	O
+in	O
+urine	O
+by	O
+gas	O
+-	O
+liquid	O
+chromatography	O
+.	O
+
+Steroids	O
+in	O
+germfree	O
+and	O
+conventional	O
+rats	O
+.	O
+
+The	O
+effects	O
+of	O
+loading	O
+the	O
+respiratory	O
+pumps	O
+on	O
+the	O
+oxygen	O
+consumption	O
+of	O
+Callionymus	O
+lyra	O
+.	O
+
+Trials	O
+of	O
+sevine	O
+activity	O
+against	O
+mosquito	O
+larvae	O
+
+The	O
+significance	O
+of	O
+structural	O
+integrity	O
+of	O
+lymphoid	O
+tissue	O
+for	O
+antibody	O
+production	O
+in	O
+culture	O
+in	O
+vivo	O
+
+Studies	O
+carried	O
+out	O
+with	O
+the	O
+Glossina	O
+morsitans	O
+colony	O
+of	O
+Lisbon	O
+.	O
+
+Transformations	O
+in	O
+the	O
+morphine	O
+series	O
+.	O
+
+Dissociative	O
+anesthetics	O
+2	O
+-	O
+(	O
+o	O
+-	O
+chlorophenyl	O
+)	O
+-	O
+2	O
+-	O
+methyl	O
+-	O
+amino	O
+cyclohexane	O
+HCL	O
+(	O
+CI	O
+-	O
+581	O
+)	O
+
+Estrus	O
+and	O
+copulative	O
+abilities	O
+of	O
+androgen	O
+-	O
+sterilized	O
+rats	O
+
+Hemodynamics	O
+changes	O
+in	O
+man	O
+during	O
+flight	O
+
+Caries	O
+prevention	O
+in	O
+the	O
+dental	O
+office	O
+.	O
+
+I	O
+.	O
+
+Clinical	O
+applications	O
+of	O
+inhibition	O
+of	O
+beta	B-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptors	I-GENE
+with	O
+propranolol	O
+.	O
+
+Automatic	O
+view	O
+box	O
+.	O
+
+Measurement	O
+of	O
+gastric	O
+acid	O
+secretion	O
+by	O
+conductivity	O
+.	O
+
+Relationship	O
+of	O
+mast	O
+cells	O
+to	O
+sarcoidosis	O
+granuloma	O
+of	O
+the	O
+skin	O
+
+Long	O
+-	O
+term	O
+effects	O
+of	O
+clofibrate	O
+(	O
+Atromid	O
+-	O
+S	O
+)	O
+on	O
+serum	O
+lipids	O
+in	O
+man	O
+.	O
+
+Phosphate	B-GENE
+glucose	I-GENE
+dehydrogenase	I-GENE
+deficiency	O
+causing	O
+hyperbilirubinemia	O
+in	O
+the	O
+newborn	O
+
+Evidence	O
+forthe	O
+electroosmosis	O
+theory	O
+of	O
+transport	O
+in	O
+the	O
+phloem	O
+.	O
+
+Effects	O
+of	O
+beta	B-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptor	I-GENE
+blockade	O
+on	O
+airway	O
+conductance	O
+and	O
+lung	O
+volume	O
+in	O
+normal	O
+and	O
+asthmatic	O
+subjects	O
+.	O
+
+I	O
+.	O
+
+Specialist	O
+in	O
+family	O
+practice	O
+-	O
+-	O
+prototype	O
+of	O
+a	O
+doctor	O
+.	O
+
+The	O
+possibility	O
+of	O
+selective	O
+chemotherapy	O
+of	O
+progressive	O
+recurring	O
+ovarian	O
+carcinoma	O
+with	O
+the	O
+aid	O
+of	O
+cytodiagnosis	O
+and	O
+incorporation	O
+of	O
+tagged	O
+idoxuridine	O
+
+Variation	O
+in	O
+the	O
+temporal	O
+-	O
+spatial	O
+distribution	O
+of	O
+228Ra	O
+and	O
+224Ra	O
+in	O
+the	O
+RES	O
+and	O
+marrow	O
+-	O
+free	O
+skeleton	O
+after	O
+incorporation	O
+of	O
+colloidal	O
+ThO2	O
+
+Oxidative	O
+degradation	O
+of	O
+adrenaline	O
+solutions	O
+:	O
+study	O
+of	O
+the	O
+intermediate	O
+stages	O
+and	O
+their	O
+analytic	O
+value	O
+for	O
+the	O
+control	O
+of	O
+this	O
+solute	O
+
+Absorption	O
+of	O
+electrolytes	O
+from	O
+the	O
+colon	O
+in	O
+cases	O
+of	O
+ulcerative	O
+colitis	O
+and	O
+in	O
+control	O
+subjects	O
+.	O
+
+Ion	O
+injection	O
+.	O
+
+Polyvinyl	O
+alcohol	O
+as	O
+a	O
+solution	O
+mediator	O
+
+Mining	O
+the	O
+diagnostic	O
+iron	O
+ore	O
+.	O
+
+The	O
+structure	O
+of	O
+digiprogenin	O
+.	O
+
+I	O
+.	O
+
+On	O
+the	O
+character	O
+of	O
+changes	O
+in	O
+the	O
+enzyme	O
+activity	O
+in	O
+the	O
+brain	O
+tissue	O
+during	O
+reflex	O
+epilepsy	O
+
+A	O
+malignant	O
+true	O
+teratoma	O
+of	O
+liver	O
+in	O
+childhood	O
+.	O
+
+Methoxyflurane	O
+and	O
+renal	O
+function	O
+
+Histochemistry	O
+and	O
+electron	O
+microscopy	O
+of	O
+acute	O
+liver	O
+lesions	O
+induced	O
+by	O
+Aflatoxin	O
+B1	O
+in	O
+ducklings	O
+.	O
+
+Functional	O
+disorders	O
+of	O
+the	O
+ureter	O
+following	O
+gynecologic	O
+surgery	O
+
+Study	O
+of	O
+the	O
+alterations	O
+of	O
+intestinal	O
+absorption	O
+,	O
+by	O
+means	O
+of	O
+I	O
+-	O
+131	O
+-	O
+triolein	O
+,	O
+in	O
+the	O
+whole	O
+body	O
+irradiated	O
+rat	O
+
+Chemical	O
+histologic	O
+and	O
+immunologic	O
+responses	O
+in	O
+rats	O
+to	O
+CC1	O
+-	O
+4	O
+by	O
+different	O
+routes	O
+of	O
+administration	O
+.	O
+
+Clinical	O
+trials	O
+with	O
+1	O
+,	O
+3	O
+-	O
+bis	O
+(	O
+2	O
+-	O
+chloroethyl	O
+)	O
+-	O
+1	O
+-	O
+nitrosourea	O
+,	O
+NSC	O
+-	O
+409962	O
+.	O
+
+Hydroxypropyl	O
+methacrylate	O
+,	O
+a	O
+new	O
+water	O
+-	O
+miscible	O
+embedding	O
+medium	O
+for	O
+electron	O
+microscopy	O
+.	O
+
+On	O
+the	O
+diagnosis	O
+of	O
+bovine	O
+leucosis	O
+and	O
+its	O
+control	O
+in	O
+southern	O
+Lower	O
+Saxony	O
+
+Experience	O
+with	O
+the	O
+restoration	O
+of	O
+agglutination	O
+properties	O
+of	O
+non	O
+-	O
+agglutinating	O
+dysenterial	O
+cultures	O
+with	O
+the	O
+use	O
+of	O
+Rzhaninov	O
+'	O
+s	O
+method	O
+
+Study	O
+on	O
+micromelias	O
+in	O
+the	O
+mouse	O
+fetus	O
+caused	O
+by	O
+x	O
+-	O
+radiation	O
+,	O
+hypoxia	O
+,	O
+trypan	O
+blue	O
+injection	O
+of	O
+hypervitaminosis	O
+-	O
+A	O
+upon	O
+mother	O
+animals	O
+during	O
+pregnancy	O
+.	O
+
+Human	O
+antitetanus	O
+serum	O
+:	O
+an	O
+unused	O
+wealth	O
+
+(	O
+3	O
+)	O
+.	O
+
+Studies	O
+on	O
+the	O
+intracutaneous	O
+infection	O
+of	O
+rabbits	O
+by	O
+Staphylococcus	O
+aureus	O
+.	O
+
+On	O
+catabolism	O
+of	O
+aminoketones	O
+in	O
+climacteric	O
+age	O
+
+The	O
+effect	O
+of	O
+feeding	O
+patterns	O
+on	O
+fat	O
+deposition	O
+in	O
+mice	O
+.	O
+
+IV	O
+.	O
+
+Studies	O
+on	O
+powdered	O
+preparations	O
+.	O
+
+A	O
+case	O
+report	O
+with	O
+angiographic	O
+follow	O
+-	O
+up	O
+study	O
+.	O
+
+Interactions	O
+between	O
+adrenergics	O
+,	O
+adrenolytics	O
+and	O
+monoamine	B-GENE
+oxidase	I-GENE
+inhibitors	O
+
+Further	O
+studies	O
+on	O
+a	O
+"	O
+new	O
+"	O
+human	O
+isoprecipitin	B-GENE
+system	O
+(	O
+Australia	O
+antigen	O
+)	O
+.	O
+
+Pigmentary	O
+rhythms	O
+as	O
+indicators	O
+of	O
+neurosecretion	O
+.	O
+
+When	O
+the	O
+cervical	O
+Pap	O
+smear	O
+is	O
+positive	O
+.	O
+
+I	O
+.	O
+
+The	O
+3	O
+-	O
+hour	O
+test	O
+iodine	O
+(	O
+I	O
+-	O
+132	O
+)	O
+uptake	O
+by	O
+the	O
+thyroid	O
+in	O
+children	O
+with	O
+growth	O
+deficiency	O
+
+Persistence	O
+of	O
+toxaphene	O
+in	O
+treated	O
+lakes	O
+.	O
+
+Studies	O
+on	O
+Coxsackie	O
+B	O
+Type	O
+5	O
+virus	O
+infections	O
+.	O
+
+Adrenergic	O
+nerve	O
+function	O
+,	O
+noradrenaline	O
+level	O
+and	O
+noradrenaline	O
+uptake	O
+in	O
+cat	O
+nictitating	O
+membrane	O
+after	O
+reserpine	O
+treatment	O
+.	O
+
+Concussion	O
+of	O
+the	O
+spinal	O
+cord	O
+
+Study	O
+on	O
+the	O
+evagination	O
+of	O
+Cysticercus	O
+pisiformis	O
+.	O
+
+The	O
+pathogenicity	O
+of	O
+Achromobacter	O
+puntatum	O
+for	O
+cold	O
+blooded	O
+and	O
+warm	O
+blooded	O
+animals	O
+
+Consanguinity	O
+and	O
+migration	O
+in	O
+the	O
+marriages	O
+of	O
+the	O
+region	O
+of	O
+Nunoa	O
+,	O
+Santiago	O
+,	O
+1850	O
+-	O
+1960	O
+
+Studies	O
+of	O
+lipogenesis	O
+by	O
+labelled	O
+precursors	O
+in	O
+the	O
+pregnant	O
+rat	O
+.	O
+
+Pharmacodynamic	O
+studies	O
+on	O
+the	O
+cardiovascular	O
+system	O
+of	O
+spontaneously	O
+hypertensive	O
+rats	O
+.	O
+
+Nuclear	O
+spin	O
+of	O
+249Bk	O
+from	O
+the	O
+hyperfine	O
+structure	O
+in	O
+its	O
+emission	O
+spectrum	O
+.	O
+
+Further	O
+observations	O
+on	O
+resorption	O
+in	O
+guinea	O
+pigs	O
+following	O
+injections	O
+of	O
+trypan	O
+blue	O
+.	O
+
+Derivatives	O
+of	O
+fluorene	O
+.	O
+
+Note	O
+on	O
+Slot	O
+'	O
+s	O
+method	O
+for	O
+the	O
+specific	O
+determination	O
+of	O
+creatinine	O
+.	O
+
+Retention	O
+behavior	O
+of	O
+steroids	O
+in	O
+gas	O
+chromatography	O
+with	O
+a	O
+series	O
+of	O
+combination	O
+columns	O
+.	O
+
+Compensatory	O
+renal	O
+hypertrophy	O
+in	O
+parabiotic	O
+rats	O
+.	O
+
+(	O
+3	O
+)	O
+.	O
+
+XXI	O
+.	O
+
+In	O
+vitro	O
+evaluation	O
+of	O
+the	O
+mucolytic	O
+action	O
+of	O
+urea	O
+.	O
+
+Electrophoretic	O
+characteriaztion	O
+of	O
+virus	O
+-	O
+induced	O
+interferon	B-GENE
+of	O
+the	O
+blood	O
+and	O
+urine	O
+in	O
+rabbits	O
+
+Iron	O
+and	O
+folate	O
+deficiency	O
+in	O
+pregnancy	O
+
+Symposium	O
+on	O
+presenile	O
+spongy	O
+encephalopathies	O
+.	O
+
+Twenty	O
+-	O
+two	O
+of	O
+the	O
+24	O
+patients	O
+had	O
+a	O
+rise	O
+in	O
+the	O
+total	O
+serum	O
+amylase	B-GENE
+following	O
+ERCP	O
+.	O
+
+Elevated	O
+maternal	B-GENE
+alpha	I-GENE
+fetoproteins	I-GENE
+and	O
+oligoamnios	O
+:	O
+fetal	O
+prognosis	O
+
+Also	O
+discussed	O
+is	O
+the	O
+possibility	O
+of	O
+a	O
+combined	O
+genetic	O
+and	O
+environmental	O
+etiology	O
+.	O
+
+Courses	O
+were	O
+repeated	O
+monthly	O
+upon	O
+recovery	O
+of	O
+myelosuppression	O
+.	O
+
+Stimulation	O
+with	O
+MCh	O
+produced	O
+a	O
+Ca	O
+-	O
+dependent	O
+transient	O
+elevation	O
+of	O
+cGMP	O
+level	O
+from	O
+10	O
+to	O
+80	O
+fmol	O
+/	O
+gland	O
+,	O
+peaking	O
+at	O
+1	O
+-	O
+2	O
+min	O
+but	O
+returning	O
+to	O
+the	O
+basal	O
+level	O
+by	O
+5	O
+min	O
+.	O
+
+Two	O
+hundred	O
+forty	O
+-	O
+three	O
+patients	O
+have	O
+received	O
+WR	O
+-	O
+2721	O
+in	O
+Phase	O
+I	O
+-	O
+II	O
+studies	O
+.	O
+
+The	O
+PEPCK	B-GENE
+promoter	O
+fragment	O
+was	O
+introduced	O
+either	O
+in	O
+the	O
+proper	O
+orientation	O
+for	O
+transcription	O
+of	O
+the	O
+TK	B-GENE
+gene	I-GENE
+or	O
+in	O
+the	O
+opposite	O
+orientation	O
+.	O
+
+Many	O
+mammary	O
+tumors	O
+induced	O
+by	O
+mouse	O
+mammary	O
+tumor	O
+virus	O
+(	O
+MMTV	O
+)	O
+contain	O
+a	O
+provirus	O
+in	O
+the	O
+same	O
+region	O
+of	O
+the	O
+host	O
+-	O
+cell	O
+genome	O
+,	O
+leading	O
+to	O
+expression	O
+of	O
+a	O
+putative	O
+cellular	O
+oncogene	O
+called	O
+int	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+these	O
+cases	O
+,	O
+asbestos	O
+or	O
+erionite	O
+-	O
+tissue	O
+burden	O
+followed	O
+by	O
+fibrosis	O
+was	O
+frequently	O
+observed	O
+.	O
+
+Hepatitis	O
+B	O
+virus	O
+and	O
+hepatoma	O
+.	O
+
+USA	O
+80	O
+,	O
+3618	O
+-	O
+3622	O
+)	O
+The	O
+two	O
+proteins	O
+show	O
+36	O
+%	O
+identities	O
+in	O
+their	O
+amino	O
+acid	O
+sequence	O
+,	O
+in	O
+an	O
+alignment	O
+requiring	O
+six	O
+gaps	O
+.	O
+
+The	O
+envelope	B-GENE
+glycoproteins	I-GENE
+of	I-GENE
+Rous	I-GENE
+sarcoma	I-GENE
+virus	I-GENE
+(	I-GENE
+RSV	I-GENE
+)	I-GENE
+,	O
+gp85	B-GENE
+and	O
+gp37	B-GENE
+,	O
+are	O
+anchored	O
+in	O
+the	O
+membrane	O
+by	O
+a	O
+27	O
+-	O
+amino	O
+acid	O
+,	O
+hydrophobic	O
+domain	O
+that	O
+lies	O
+adjacent	O
+to	O
+a	O
+22	O
+-	O
+amino	O
+acid	O
+,	O
+cytoplasmic	O
+domain	O
+at	O
+the	O
+carboxy	O
+terminus	O
+of	O
+gp37	B-GENE
+.	O
+
+The	O
+drug	O
+was	O
+given	O
+in	O
+a	O
+daily	O
+oral	O
+dose	O
+of	O
+0	O
+.	O
+5	O
+g	O
+/	O
+m2	O
+,	O
+3	O
+.	O
+5	O
+h	O
+prior	O
+to	O
+each	O
+radiation	O
+treatment	O
+.	O
+
+Histogenetic	O
+aspects	O
+of	O
+mesoblastic	O
+nephroma	O
+.	O
+
+Effect	O
+of	O
+acute	O
+and	O
+chronic	O
+psychogenic	O
+stress	O
+on	O
+corticoadrenal	O
+and	O
+pituitary	B-GENE
+-	I-GENE
+thyroid	I-GENE
+hormones	I-GENE
+in	O
+male	O
+rats	O
+.	O
+
+An	O
+intact	O
+5	O
+.	O
+7	O
+-	O
+kb	O
+provirus	O
+of	O
+the	O
+avian	O
+erythroblastosis	O
+virus	O
+E26	O
+has	O
+been	O
+molecularly	O
+cloned	O
+for	O
+comparisons	O
+with	O
+avian	O
+myeloblastosis	O
+virus	O
+(	O
+AMV	O
+)	O
+and	O
+other	O
+avian	O
+tumor	O
+viruses	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+haloperidol	O
+selectively	O
+reduced	O
+the	O
+animal	O
+'	O
+s	O
+capacity	O
+to	O
+'	O
+programme	O
+non	O
+-	O
+stimulus	O
+directed	O
+motor	O
+behaviour	O
+'	O
+.	O
+
+Neither	O
+side	O
+effect	O
+nor	O
+abnormal	O
+laboratory	O
+findings	O
+due	O
+to	O
+this	O
+drug	O
+were	O
+observed	O
+.	O
+
+The	O
+results	O
+presented	O
+in	O
+this	O
+report	O
+suggest	O
+that	O
+the	O
+SV40	O
+G	O
+-	O
+C	O
+-	O
+rich	O
+sequences	O
+can	O
+function	O
+as	O
+independent	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+transcriptional	O
+-	O
+control	O
+elements	O
+.	O
+
+Construction	O
+of	O
+human	O
+cell	O
+lines	O
+which	O
+contain	O
+and	O
+express	O
+the	O
+adenovirus	O
+DNA	O
+binding	O
+protein	O
+gene	O
+by	O
+cotransformation	O
+with	O
+the	O
+HSV	B-GENE
+-	I-GENE
+1	I-GENE
+tk	I-GENE
+gene	I-GENE
+.	O
+
+Diagnosis	O
+and	O
+treatment	O
+of	O
+insulin	B-GENE
+-	O
+secreting	O
+tumours	O
+.	O
+
+Theories	O
+proffered	O
+to	O
+account	O
+for	O
+the	O
+modality	O
+shift	O
+effect	O
+are	O
+critically	O
+evaluated	O
+.	O
+
+The	O
+effects	O
+of	O
+cardioselective	O
+beta	O
+-	O
+1	O
+adrenergic	O
+agonist	O
+,	O
+1	O
+-	O
+(	O
+4	O
+-	O
+hydroxyphenoxy	O
+)	O
+-	O
+isopropylamino	O
+-	O
+2	O
+-	O
+propanol	O
+)	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+prenalterol	O
+,	O
+were	O
+examined	O
+on	O
+direct	O
+and	O
+continuous	O
+measurements	O
+of	O
+left	O
+ventricular	O
+(	O
+LV	O
+)	O
+pressure	O
+,	O
+diameter	O
+,	O
+dP	O
+/	O
+dt	O
+,	O
+velocity	O
+of	O
+shortening	O
+,	O
+arterial	O
+pressure	O
+,	O
+iliac	O
+blood	O
+flow	O
+and	O
+heart	O
+rate	O
+in	O
+10	O
+conscious	O
+dogs	O
+.	O
+
+Endorphins	B-GENE
+at	O
+the	O
+approach	O
+of	O
+death	O
+.	O
+
+Trial	O
+treatment	O
+of	O
+schizophrenia	O
+with	O
+des	B-GENE
+-	I-GENE
+Tyr	I-GENE
+-	I-GENE
+gamma	I-GENE
+-	I-GENE
+endorphin	I-GENE
+
+Cardiac	O
+taurine	O
+levels	O
+and	O
+sarcolemmal	O
+calcium	O
+binding	O
+activity	O
+in	O
+furazolidone	O
+-	O
+induced	O
+cardiomyopathy	O
+.	O
+
+Separation	O
+of	O
+malaria	O
+-	O
+infected	O
+erythrocytes	O
+from	O
+whole	O
+blood	O
+:	O
+use	O
+of	O
+a	O
+selective	O
+high	O
+-	O
+gradient	O
+magnetic	O
+separation	O
+technique	O
+.	O
+
+The	O
+roll	O
+-	O
+over	O
+test	O
+to	O
+predict	O
+toxemia	O
+in	O
+pregnancy	O
+.	O
+
+Can	O
+thyroglobulin	B-GENE
+assay	O
+really	O
+supplant	O
+radioiodine	O
+scans	O
+in	O
+patients	O
+with	O
+differentiated	O
+thyroid	O
+cancer	O
+?	O
+
+3	O
+Significant	O
+reductions	O
+in	O
+lying	O
+mean	O
+arterial	O
+blood	O
+pressure	O
+were	O
+observed	O
+with	O
+daily	O
+doses	O
+of	O
+200	O
+mg	O
+(	O
+-	O
+9	O
+%	O
+)	O
+,	O
+400	O
+mg	O
+(	O
+-	O
+10	O
+%	O
+)	O
+and	O
+800	O
+mg	O
+(	O
+-	O
+14	O
+%	O
+)	O
+,	O
+and	O
+were	O
+associated	O
+with	O
+significant	O
+decreases	O
+in	O
+heart	O
+rate	O
+and	O
+plasma	B-GENE
+renin	I-GENE
+activity	O
+.	O
+
+Isolation	O
+of	O
+Aeromonas	O
+from	O
+faeces	O
+.	O
+
+(	O
+iii	O
+)	O
+The	O
+mRNA	O
+is	O
+not	O
+efficiently	O
+polyadenylated	O
+at	O
+sequences	O
+in	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+DHFR	B-GENE
+cDNA	I-GENE
+but	O
+rather	O
+uses	O
+polyadenylation	O
+signals	O
+downstream	O
+from	O
+the	O
+DHFR	B-GENE
+cDNA	I-GENE
+.	O
+
+At	O
+both	O
+water	O
+temperatures	O
+,	O
+VO2	O
+increased	O
+linearly	O
+with	O
+increasing	O
+swimming	O
+velocity	O
+.	O
+
+Brief	O
+report	O
+.	O
+
+Hybrid	O
+-	O
+selection	O
+experiments	O
+against	O
+total	O
+PB	O
+-	O
+inducible	O
+RNA	O
+were	O
+performed	O
+with	O
+plasmid	O
+DNA	O
+derived	O
+from	O
+clones	O
+enriched	O
+in	O
+PB	O
+-	O
+inducible	O
+information	O
+.	O
+
+Risk	O
+of	O
+HTLV	O
+infection	O
+in	O
+patients	O
+on	O
+haemodialysis	O
+.	O
+
+In	O
+vitro	O
+metabolism	O
+of	O
+progesterone	O
+by	O
+the	O
+human	O
+undescended	O
+testis	O
+.	O
+
+Two	O
+patients	O
+withdrew	O
+from	O
+therapy	O
+,	O
+one	O
+for	O
+personal	O
+reasons	O
+and	O
+one	O
+because	O
+a	O
+paraspinal	O
+mass	O
+developed	O
+.	O
+
+All	O
+patients	O
+received	O
+VCR	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+m2	O
+weekly	O
+for	O
+6	O
+weeks	O
+with	O
+dose	O
+modification	O
+for	O
+neurotoxicity	O
+.	O
+
+Glutamic	O
+acid	O
+in	O
+a	O
+dose	O
+of	O
+1	O
+/	O
+100	O
+of	O
+the	O
+LD50	O
+was	O
+injected	O
+in	O
+the	O
+form	O
+of	O
+sodium	O
+salt	O
+into	O
+male	O
+and	O
+female	O
+Wistar	O
+rats	O
+for	O
+7	O
+days	O
+after	O
+8	O
+-	O
+and	O
+12	O
+-	O
+day	O
+injections	O
+of	O
+dexazone	O
+.	O
+
+Serum	O
+ascorbic	O
+acid	O
+had	O
+an	O
+inverse	O
+and	O
+the	O
+strongest	O
+association	O
+with	O
+systolic	O
+blood	O
+pressure	O
+among	O
+the	O
+risk	O
+factors	O
+including	O
+blood	O
+pressure	O
+,	O
+total	O
+cholesterol	O
+,	O
+triglyceride	O
+,	O
+gamma	B-GENE
+-	I-GENE
+GTP	I-GENE
+and	O
+obesity	O
+.	O
+
+Effect	O
+of	O
+bromazepam	O
+on	O
+growth	B-GENE
+hormone	I-GENE
+and	O
+prolactin	B-GENE
+secretion	O
+in	O
+normal	O
+subjects	O
+.	O
+
+In	O
+several	O
+cases	O
+of	O
+definite	O
+SjS	O
+,	O
+labial	O
+salivary	O
+gland	O
+examinations	O
+after	O
+more	O
+than	O
+a	O
+one	O
+year	O
+interval	O
+were	O
+performed	O
+on	O
+two	O
+occasions	O
+,	O
+and	O
+the	O
+clinical	O
+and	O
+histopathological	O
+changes	O
+were	O
+investigated	O
+.	O
+
+All	O
+radiologists	O
+using	O
+the	O
+machine	O
+found	O
+that	O
+the	O
+reporting	O
+terminal	O
+was	O
+simple	O
+to	O
+operate	O
+,	O
+but	O
+found	O
+that	O
+reporting	O
+abnormalities	O
+caused	O
+an	O
+increased	O
+effort	O
+and	O
+took	O
+a	O
+longer	O
+time	O
+.	O
+
+Thalamotomy	O
+aiming	O
+at	O
+the	O
+CM	O
+-	O
+Pf	O
+complex	O
+and	O
+using	O
+stereotactic	O
+gamma	O
+irradiation	O
+has	O
+been	O
+performed	O
+in	O
+a	O
+series	O
+of	O
+52	O
+patients	O
+with	O
+severe	O
+pain	O
+due	O
+to	O
+malignancy	O
+.	O
+
+2	O
+Silastic	O
+capsules	O
+,	O
+each	O
+containing	O
+22	O
+-	O
+23	O
+mg	O
+of	O
+ethinyl	O
+estradiol	O
+,	O
+were	O
+inserted	O
+subcutaneously	O
+in	O
+5	O
+men	O
+with	O
+benign	O
+prostatic	O
+hypertrophy	O
+.	O
+
+When	O
+used	O
+subcutaneously	O
+or	O
+intravenously	O
+in	O
+maximum	O
+tolerated	O
+doses	O
+the	O
+antibiotic	O
+inhibited	O
+the	O
+development	O
+of	O
+lymphadenosis	O
+NK	O
+/	O
+Li	O
+by	O
+90	O
+and	O
+70	O
+per	O
+cent	O
+respectively	O
+.	O
+
+Effect	O
+of	O
+2	O
+-	O
+(	O
+p	O
+-	O
+chlorophenyl	O
+)	O
+cyclopropylamine	O
+on	O
+5	O
+-	O
+hydroxyindole	O
+concentration	O
+and	O
+monoamine	B-GENE
+oxidase	I-GENE
+activity	O
+in	O
+rat	O
+brain	O
+.	O
+
+Then	O
+,	O
+pure	O
+pancreatic	O
+juice	O
+was	O
+infused	O
+into	O
+the	O
+duodenum	O
+.	O
+
+An	O
+experiment	O
+was	O
+carried	O
+on	O
+133	O
+grown	O
+up	O
+fowls	O
+and	O
+broilers	O
+from	O
+4	O
+industrial	O
+farms	O
+,	O
+vaccinated	O
+with	O
+spray	O
+lento	O
+and	O
+mesogenic	O
+vaccines	O
+for	O
+straining	O
+the	O
+immunity	O
+against	O
+pseodopest	O
+through	O
+RIHA	O
+and	O
+provoking	O
+pseudoplague	O
+with	O
+a	O
+pathogenic	O
+virus	O
+.	O
+
+(	O
+2	O
+)	O
+The	O
+inappropriateness	O
+of	O
+adaptive	O
+segmentation	O
+for	O
+the	O
+isolation	O
+of	O
+spikes	O
+and	O
+sharp	O
+waves	O
+,	O
+which	O
+had	O
+been	O
+anticipated	O
+in	O
+view	O
+of	O
+the	O
+short	O
+duration	O
+of	O
+such	O
+transients	O
+in	O
+relation	O
+to	O
+the	O
+length	O
+of	O
+the	O
+window	O
+(	O
+1	O
+.	O
+2	O
+sec	O
+)	O
+used	O
+for	O
+the	O
+autocorrelation	O
+functions	O
+employed	O
+in	O
+the	O
+segmentation	O
+algorithm	O
+,	O
+was	O
+confirmed	O
+.	O
+
+The	O
+ability	O
+of	O
+chronic	O
+UM	O
+-	O
+272	O
+(	O
+dimethylpropranolol	O
+)	O
+treatment	O
+to	O
+prevent	O
+the	O
+induction	O
+of	O
+reentrant	O
+ventricular	O
+tachyarrhythmias	O
+was	O
+assessed	O
+in	O
+the	O
+conscious	O
+dog	O
+subjected	O
+to	O
+serial	O
+programmed	O
+electrical	O
+stimulation	O
+on	O
+days	O
+3	O
+-	O
+-	O
+5	O
+after	O
+myocardial	O
+infarction	O
+.	O
+
+The	O
+effect	O
+of	O
+echothiophate	O
+on	O
+the	O
+biphasic	O
+response	O
+of	O
+rabbit	O
+ocular	O
+pressure	O
+to	O
+dipivefrin	O
+.	O
+
+In	O
+most	O
+cases	O
+of	O
+acute	O
+transmural	O
+infarction	O
+,	O
+the	O
+reciprocal	O
+ST	O
+segment	O
+depressions	O
+observed	O
+in	O
+contralateral	O
+leads	O
+are	O
+less	O
+marked	O
+than	O
+the	O
+primary	O
+ST	O
+segment	O
+elevations	O
+.	O
+
+Bacillus	O
+cereus	O
+cross	O
+-	O
+infection	O
+in	O
+a	O
+maternity	O
+-	O
+unit	O
+.	O
+
+In	O
+the	O
+latter	O
+category	O
+particular	O
+emphasis	O
+is	O
+being	O
+placed	O
+on	O
+new	O
+anthracycline	O
+analogues	O
+of	O
+doxorubicin	O
+and	O
+analogues	O
+of	O
+cisplatinum	O
+diammine	O
+dichloride	O
+.	O
+
+Late	O
+mRNA	O
+selected	O
+by	O
+a	O
+cDNA	O
+homologous	O
+to	O
+the	O
+HindIII	B-GENE
+-	I-GENE
+P	I-GENE
+/	O
+EcoRI	B-GENE
+-	I-GENE
+B	I-GENE
+region	O
+of	O
+the	O
+AcNPV	O
+map	O
+directed	O
+the	O
+synthesis	O
+of	O
+31K	O
+and	O
+30K	O
+proteins	O
+which	O
+comigrated	O
+with	O
+the	O
+31K	O
+and	O
+30K	O
+proteins	O
+translated	O
+from	O
+RNA	O
+selected	O
+by	O
+the	O
+HindIII	B-GENE
+-	I-GENE
+A	I-GENE
+/	O
+EcoRI	B-GENE
+-	I-GENE
+C	I-GENE
+/	O
+SstI	B-GENE
+-	I-GENE
+G	I-GENE
+cDNA	O
+.	O
+
+Intraoperatively	O
+the	O
+complement	B-GENE
+factor	I-GENE
+C3c	I-GENE
+decreased	O
+by	O
+20	O
+%	O
+,	O
+while	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+antitrypsin	I-GENE
+showed	O
+postoperatively	O
+an	O
+increase	O
+by	O
+30	O
+%	O
+.	O
+
+A	O
+polypeptide	O
+chain	O
+of	O
+34	O
+residues	O
+of	O
+the	O
+deduced	O
+yeast	O
+amino	O
+acid	O
+sequence	O
+closely	O
+resembles	O
+a	O
+peptide	O
+sequence	O
+at	O
+the	O
+ADP	O
+binding	O
+site	O
+of	O
+bovine	B-GENE
+muscle	I-GENE
+pyruvate	I-GENE
+kinase	I-GENE
+.	O
+
+The	O
+P165	O
+component	O
+,	O
+however	O
+,	O
+could	O
+be	O
+differentiated	O
+from	O
+the	O
+two	O
+later	O
+components	O
+since	O
+it	O
+increased	O
+in	O
+amplitude	O
+with	O
+increased	O
+task	O
+demands	O
+while	O
+the	O
+N2	O
+and	O
+P3	O
+amplitudes	O
+remained	O
+constant	O
+.	O
+
+Differential	O
+drawing	O
+size	O
+associated	O
+with	O
+unilateral	O
+brain	O
+damage	O
+.	O
+
+The	O
+intracoronary	O
+administration	O
+of	O
+both	O
+drugs	O
+markedly	O
+reduced	O
+the	O
+incidence	O
+of	O
+VF	O
+induced	O
+by	O
+the	O
+release	O
+of	O
+a	O
+40	O
+-	O
+min	O
+coronary	O
+artery	O
+occlusion	O
+.	O
+
+These	O
+fusions	O
+are	O
+contained	O
+on	O
+plasmids	O
+which	O
+have	O
+both	O
+yeast	O
+and	O
+E	O
+.	O
+coli	O
+replication	O
+origins	O
+and	O
+selectable	O
+markers	O
+and	O
+,	O
+therefore	O
+,	O
+can	O
+be	O
+used	O
+to	O
+transform	O
+either	O
+yeast	O
+or	O
+E	O
+.	O
+coli	O
+cells	O
+.	O
+
+Therefore	O
+,	O
+it	O
+was	O
+concluded	O
+that	O
+thrombotic	O
+tendency	O
+certainly	O
+existed	O
+in	O
+patients	O
+with	O
+MS	O
+compared	O
+to	O
+those	O
+with	O
+non	O
+RHD	O
+and	O
+that	O
+it	O
+was	O
+one	O
+of	O
+the	O
+causes	O
+of	O
+the	O
+significantly	O
+high	O
+incidence	O
+of	O
+thromboembolism	O
+in	O
+comparison	O
+with	O
+non	O
+RHD	O
+.	O
+
+Subdural	O
+electrodes	O
+may	O
+yield	O
+larger	O
+VEP	O
+amplitudes	O
+than	O
+skull	O
+or	O
+scalp	O
+electrodes	O
+.	O
+
+Products	O
+of	O
+immune	O
+cells	O
+such	O
+as	O
+transfer	B-GENE
+factor	I-GENE
+and	O
+lymphokines	O
+form	O
+the	O
+third	O
+and	O
+possibly	O
+most	O
+important	O
+group	O
+of	O
+immune	O
+-	O
+stimulating	O
+agents	O
+.	O
+
+Use	O
+of	O
+the	O
+immunofluorescence	O
+method	O
+for	O
+identification	O
+of	O
+enteroviruses	O
+in	O
+cell	O
+cultures	O
+
+This	O
+fraction	O
+is	O
+resistant	O
+to	O
+digestions	O
+by	O
+DNase	B-GENE
+I	I-GENE
+and	O
+RNase	B-GENE
+T1	I-GENE
+and	O
+disappears	O
+completely	O
+upon	O
+alkali	O
+hydrolysis	O
+.	O
+
+The	O
+construction	O
+of	O
+a	O
+small	O
+library	O
+of	O
+mouse	O
+repetitive	O
+DNA	O
+has	O
+been	O
+previously	O
+reported	O
+(	O
+Pietras	O
+et	O
+al	O
+.	O
+,	O
+Nucleic	O
+Acids	O
+Res	O
+.	O
+
+No	O
+direct	O
+repeats	O
+flank	O
+the	O
+pseudogene	O
+in	O
+the	O
+U2	B-GENE
+/	I-GENE
+4	I-GENE
+locus	I-GENE
+.	O
+
+The	O
+direct	O
+effects	O
+of	O
+transmitter	O
+release	O
+were	O
+(	O
+a	O
+)	O
+an	O
+early	O
+fall	O
+in	O
+MAP	O
+followed	O
+by	O
+a	O
+late	O
+pressor	O
+effect	O
+;	O
+and	O
+(	O
+b	O
+)	O
+an	O
+early	O
+bradycardia	O
+followed	O
+by	O
+a	O
+late	O
+tachycardia	O
+.	O
+
+The	O
+number	O
+of	O
+elements	O
+and	O
+their	O
+sizes	O
+relative	O
+to	O
+the	O
+configuration	O
+were	O
+varied	O
+in	O
+a	O
+series	O
+of	O
+five	O
+experiments	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+overall	O
+chance	O
+that	O
+a	O
+patient	O
+would	O
+undergo	O
+ET	O
+was	O
+greater	O
+in	O
+a	O
+cycle	O
+in	O
+which	O
+more	O
+than	O
+one	O
+follicle	O
+20	O
+mm	O
+or	O
+larger	O
+was	O
+developing	O
+than	O
+in	O
+a	O
+cycle	O
+in	O
+which	O
+a	O
+single	O
+large	O
+follicle	O
+was	O
+developing	O
+.	O
+
+Five	O
+of	O
+the	O
+patients	O
+with	O
+increased	O
+L	O
+-	O
+L	O
+size	O
+had	O
+a	O
+normal	O
+A	O
+-	O
+P	O
+diameter	O
+.	O
+
+Immunochemotherapy	O
+with	O
+schizophyllan	O
+(	O
+SPG	O
+)	O
+combined	O
+with	O
+chemotherapeutic	O
+agents	O
+was	O
+evaluated	O
+in	O
+two	O
+syngeneic	O
+tumor	O
+-	O
+C3H	O
+/	O
+He	O
+mouse	O
+systems	O
+.	O
+
+However	O
+,	O
+when	O
+combined	O
+with	O
+mitomycin	O
+C	O
+given	O
+with	O
+1	O
+to	O
+5	O
+-	O
+days	O
+interval	O
+,	O
+the	O
+concurrent	O
+administration	O
+of	O
+SPG	O
+prolonged	O
+significantly	O
+the	O
+life	O
+-	O
+span	O
+of	O
+the	O
+tumor	O
+-	O
+bearing	O
+mice	O
+.	O
+
+Data	O
+are	O
+presented	O
+hinting	O
+that	O
+the	O
+15	O
+beta	O
+-	O
+hydroxy	O
+-	O
+,	O
+metabolite	O
+of	O
+CPA	O
+may	O
+actually	O
+be	O
+the	O
+biologically	O
+active	O
+agent	O
+.	O
+
+In	O
+contrast	O
+,	O
+in	O
+LL	O
+patients	O
+during	O
+ENL	O
+the	O
+ConA	B-GENE
+-	O
+induced	O
+suppressor	O
+response	O
+was	O
+markedly	O
+reduced	O
+.	O
+
+Functional	O
+characterization	O
+of	O
+a	O
+fraction	O
+identified	O
+by	O
+its	O
+activity	O
+in	O
+a	O
+second	O
+template	O
+rescue	O
+assay	O
+.	O
+
+It	O
+has	O
+been	O
+established	O
+that	O
+preoperative	O
+irradiation	O
+in	O
+the	O
+form	O
+of	O
+the	O
+fractionation	O
+of	O
+a	O
+single	O
+focal	O
+dose	O
+of	O
+6	O
+Gy	O
+every	O
+other	O
+day	O
+,	O
+the	O
+summary	O
+dose	O
+of	O
+24	O
+Gy	O
+within	O
+8	O
+-	O
+10	O
+days	O
+followed	O
+by	O
+surgery	O
+1	O
+-	O
+3	O
+days	O
+after	O
+irradiation	O
+does	O
+not	O
+either	O
+complicate	O
+its	O
+performance	O
+or	O
+the	O
+course	O
+of	O
+the	O
+postoperative	O
+period	O
+,	O
+and	O
+by	O
+the	O
+short	O
+-	O
+and	O
+long	O
+-	O
+term	O
+results	O
+it	O
+is	O
+no	O
+worse	O
+than	O
+the	O
+routine	O
+dose	O
+fractionation	O
+.	O
+
+Fibrin	B-GENE
+gels	O
+and	O
+their	O
+possible	O
+implication	O
+for	O
+surface	O
+hemorheology	O
+in	O
+health	O
+and	O
+disease	O
+.	O
+
+Hepatitis	O
+-	O
+B	O
+vaccination	O
+in	O
+the	O
+elderly	O
+.	O
+
+Radiogallium	O
+imaging	O
+is	O
+thus	O
+of	O
+limited	O
+use	O
+in	O
+evaluation	O
+of	O
+suspected	O
+giant	O
+cell	O
+tumors	O
+of	O
+bone	O
+.	O
+
+Ventricular	O
+volume	O
+stiffness	O
+vs	O
+.	O
+the	O
+mean	O
+wall	O
+stress	O
+relationship	O
+of	O
+LVH	O
+shifted	O
+upward	O
+,	O
+whereas	O
+the	O
+normalized	O
+wall	O
+muscle	O
+stiffness	O
+vs	O
+.	O
+the	O
+mean	O
+wall	O
+stress	O
+relationship	O
+of	O
+LVH	O
+showed	O
+a	O
+smaller	O
+slope	O
+.	O
+
+Synthesis	O
+of	O
+(	O
++	O
+)	O
+-	O
+lysergic	O
+acid	O
+diethylamide	O
+tartrate	O
+
+Weight	O
+loss	O
+reduces	O
+arterial	O
+pressure	O
+by	O
+a	O
+decrease	O
+in	O
+intravascular	O
+volume	O
+and	O
+cardiac	O
+output	O
+associated	O
+with	O
+a	O
+fall	O
+in	O
+sympathetic	O
+activity	O
+.	O
+
+The	O
+effect	O
+of	O
+treatment	O
+may	O
+thus	O
+be	O
+divided	O
+into	O
+two	O
+main	O
+phases	O
+-	O
+-	O
+an	O
+initial	O
+phase	O
+with	O
+a	O
+reduction	O
+in	O
+LV	O
+mass	O
+and	O
+a	O
+reduction	O
+in	O
+cardiac	O
+output	O
+and	O
+no	O
+change	O
+in	O
+total	O
+peripheral	O
+resistance	O
+-	O
+-	O
+and	O
+a	O
+second	O
+phase	O
+with	O
+a	O
+constant	O
+LV	O
+mass	O
+but	O
+an	O
+increase	O
+in	O
+cardiac	O
+output	O
+to	O
+the	O
+pretreatment	O
+level	O
+again	O
+and	O
+a	O
+concomitant	O
+decrease	O
+in	O
+total	O
+peripheral	O
+resistance	O
+.	O
+
+This	O
+study	O
+was	O
+undertaken	O
+to	O
+assess	O
+the	O
+effects	O
+of	O
+hypothermia	O
+and	O
+chemical	O
+cardioplegia	O
+on	O
+the	O
+functional	O
+recovery	O
+of	O
+hypertrophied	O
+non	O
+-	O
+failing	O
+rat	O
+hearts	O
+subjected	O
+to	O
+an	O
+extended	O
+period	O
+of	O
+global	O
+ischaemia	O
+.	O
+
+Oxygen	O
+profiles	O
+calculated	O
+for	O
+the	O
+Krogh	O
+model	O
+with	O
+excentric	O
+diffusion	O
+were	O
+similar	O
+to	O
+those	O
+derived	O
+for	O
+the	O
+two	O
+models	O
+of	O
+concentric	O
+diffusion	O
+.	O
+
+Cultivation	O
+technics	O
+for	O
+Codonopsis	O
+pilosula	O
+
+Radioimmunoassay	O
+of	O
+serum	O
+creatine	B-GENE
+kinase	I-GENE
+B	I-GENE
+isoenzyme	I-GENE
+in	O
+the	O
+diagnosis	O
+of	O
+acute	O
+myocardial	O
+infarction	O
+.	O
+
+Selective	O
+macrophage	O
+inhibition	O
+abolishes	O
+warfarin	O
+-	O
+induced	O
+reduction	O
+of	O
+metastasis	O
+.	O
+
+Restriction	O
+enzyme	O
+and	O
+heteroduplex	O
+analyses	O
+confirmed	O
+that	O
+sequences	O
+unique	O
+to	O
+FeSV	O
+(	O
+src	B-GENE
+sequences	I-GENE
+)	O
+are	O
+located	O
+at	O
+the	O
+center	O
+of	O
+the	O
+FeSV	O
+genome	O
+and	O
+are	O
+approximately	O
+1	O
+.	O
+5	O
+kilobase	O
+pairs	O
+in	O
+length	O
+.	O
+
+Catecholamines	O
+and	O
+aversive	O
+learning	O
+:	O
+a	O
+review	O
+.	O
+
+A	O
+haemolytic	O
+enterotoxigenic	O
+strain	O
+of	O
+E	O
+.	O
+coli	O
+(	O
+O149	O
+:	O
+K88	O
+:	O
+H10	O
+)	O
+was	O
+regularly	O
+recovered	O
+from	O
+piglets	O
+with	O
+PWD	O
+while	O
+rotavirus	O
+was	O
+demonstrated	O
+on	O
+a	O
+number	O
+of	O
+occasions	O
+.	O
+
+The	O
+antibody	O
+titer	O
+of	O
+202	O
+chickens	O
+to	O
+SA	O
+-	O
+11	O
+rotavirus	O
+was	O
+determined	O
+by	O
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+blocking	O
+assay	O
+.	O
+
+Poly	O
+(	O
+dT	O
+)	O
+and	O
+denatured	O
+calf	O
+thymus	O
+DNA	O
+were	O
+more	O
+effective	O
+than	O
+were	O
+other	O
+polynucleotides	O
+tested	O
+in	O
+promoting	O
+accumulation	O
+of	O
+19	O
+HDP	B-GENE
+*	I-GENE
+;	O
+(	O
+dT	O
+)	O
+8	O
+was	O
+as	O
+effective	O
+as	O
+were	O
+longer	O
+molecules	O
+of	O
+(	O
+dT	O
+)	O
+n	O
+,	O
+but	O
+(	O
+dT	O
+)	O
+4	O
+and	O
+(	O
+dT	O
+)	O
+6	O
+were	O
+much	O
+less	O
+effective	O
+,	O
+indicating	O
+that	O
+the	O
+binding	O
+site	O
+involved	O
+in	O
+19	O
+HDP	B-GENE
+*	I-GENE
+accumulation	O
+covered	O
+between	O
+6	O
+and	O
+8	O
+residues	O
+of	O
+(	O
+dT	O
+)	O
+n	O
+.	O
+
+A	O
+double	O
+-	O
+blind	O
+trial	O
+of	O
+half	O
+-	O
+strength	O
+Polybactrin	O
+Soluble	O
+GU	O
+bladder	O
+irrigation	O
+in	O
+cystoscopy	O
+.	O
+
+Thus	O
+it	O
+appears	O
+that	O
+insertion	O
+of	O
+a	O
+transposable	O
+element	O
+near	O
+the	O
+5	O
+'	O
+terminus	O
+of	O
+the	O
+structural	O
+gene	O
+can	O
+produce	O
+constitutive	O
+expression	O
+of	O
+a	O
+normally	O
+glucose	O
+-	O
+repressed	O
+enzyme	O
+.	O
+
+Five	O
+experiments	O
+examined	O
+the	O
+influence	O
+of	O
+opiate	O
+antagonists	O
+on	O
+both	O
+the	O
+short	O
+-	O
+term	O
+analgesic	O
+reaction	O
+resulting	O
+30	O
+min	O
+after	O
+exposure	O
+to	O
+inescapable	O
+shock	O
+and	O
+the	O
+long	O
+-	O
+term	O
+analgesic	O
+reaction	O
+resulting	O
+after	O
+reexposure	O
+to	O
+shock	O
+24	O
+hr	O
+after	O
+inescapable	O
+shock	O
+exposure	O
+.	O
+
+Experiment	O
+3	O
+showed	O
+that	O
+the	O
+long	O
+-	O
+term	O
+analgesic	O
+reaction	O
+could	O
+also	O
+be	O
+reduced	O
+by	O
+administration	O
+of	O
+naltrexone	O
+prior	O
+to	O
+reexposure	O
+to	O
+shock	O
+.	O
+
+A	O
+22K	O
+polypeptide	O
+was	O
+detected	O
+as	O
+a	O
+translation	O
+product	O
+of	O
+late	O
+RNA	O
+that	O
+hybridized	O
+to	O
+this	O
+DNA	O
+fragment	O
+.	O
+
+Replicating	O
+simian	O
+virus	O
+40	O
+(	O
+SV40	O
+)	O
+chromosomes	O
+were	O
+found	O
+to	O
+be	O
+similar	O
+to	O
+other	O
+eukaryotic	O
+chromosomes	O
+in	O
+that	O
+the	O
+rate	O
+and	O
+extent	O
+of	O
+micrococcal	B-GENE
+nuclease	I-GENE
+(	O
+MNase	B-GENE
+)	O
+digestion	O
+were	O
+greater	O
+with	O
+replicating	O
+than	O
+with	O
+nonreplicating	O
+mature	O
+SV40	O
+chromatin	O
+.	O
+
+A	O
+hypothesis	O
+.	O
+
+Physiology	O
+and	O
+Physiopathology	O
+
+The	O
+genome	O
+of	O
+avian	O
+erythroblastosis	O
+virus	O
+contains	O
+two	O
+independently	O
+expressed	O
+genetic	O
+loci	O
+(	O
+v	B-GENE
+-	I-GENE
+erbA	I-GENE
+and	O
+v	B-GENE
+-	I-GENE
+erbB	I-GENE
+)	O
+whose	O
+activities	O
+are	O
+probably	O
+responsible	O
+for	O
+oncogenesis	O
+by	O
+the	O
+virus	O
+.	O
+
+Because	O
+RNase	B-GENE
+III	I-GENE
+host	I-GENE
+mutants	I-GENE
+are	O
+defective	O
+in	O
+sib	B-GENE
+regulation	O
+,	O
+processing	O
+of	O
+the	O
+PL	B-GENE
+mRNA	I-GENE
+at	O
+sib	B-GENE
+by	O
+this	O
+endoribonuclease	O
+may	O
+cause	O
+int	B-GENE
+mRNA	I-GENE
+decay	O
+and	O
+decrease	O
+int	B-GENE
+synthesis	O
+.	O
+
+At	O
+least	O
+one	O
+clone	O
+,	O
+lambda	O
+HHG	O
+41	O
+,	O
+contains	O
+,	O
+in	O
+addition	O
+to	O
+the	O
+histone	B-GENE
+genes	I-GENE
+,	O
+a	O
+region	O
+that	O
+hybridizes	O
+with	O
+a	O
+cytoplasmic	O
+RNA	O
+approximately	O
+330	O
+nucleotides	O
+in	O
+length	O
+.	O
+
+Both	O
+neural	O
+and	O
+hormonal	O
+pathways	O
+and	O
+both	O
+opiate	O
+and	O
+nonopiate	O
+substances	O
+play	O
+roles	O
+in	O
+the	O
+complex	O
+modulation	O
+of	O
+pain	O
+transmission	O
+.	O
+
+Restoration	O
+of	O
+impaired	O
+immune	O
+functions	O
+in	O
+aging	O
+animals	O
+.	O
+
+Postoperative	O
+serum	O
+ACTH	B-GENE
+levels	O
+were	O
+normal	O
+.	O
+
+In	O
+fact	O
+,	O
+families	O
+of	O
+polypeptides	O
+were	O
+produced	O
+by	O
+initiation	O
+of	O
+translation	O
+at	O
+AUG	O
+codons	O
+within	O
+sequences	O
+coding	O
+for	O
+VP1	B-GENE
+and	O
+T	B-GENE
+,	O
+presumably	O
+as	O
+a	O
+result	O
+of	O
+transcription	O
+initiation	O
+events	O
+that	O
+generated	O
+5	O
+'	O
+ends	O
+immediately	O
+upstream	O
+from	O
+these	O
+AUGs	O
+.	O
+
+In	O
+addition	O
+,	O
+TRP1	B-GENE
+RI	O
+Circle	O
+DNA	O
+is	O
+organized	O
+into	O
+nucleosomes	O
+whose	O
+size	O
+and	O
+spacing	O
+are	O
+indistinguishable	O
+from	O
+that	O
+of	O
+bulk	O
+yeast	O
+chromatin	O
+.	O
+
+The	O
+frequency	O
+of	O
+previous	O
+transfusion	O
+in	O
+chronic	O
+hepatitis	O
+,	O
+cirrhosis	O
+and	O
+hepatocellular	O
+carcinoma	O
+of	O
+type	O
+NANB	O
+was	O
+42	O
+.	O
+8	O
+,	O
+37	O
+.	O
+1	O
+and	O
+15	O
+.	O
+1	O
+%	O
+,	O
+respectively	O
+,	O
+whereas	O
+the	O
+incidence	O
+of	O
+early	O
+posttransfusion	O
+hepatitis	O
+was	O
+8	O
+.	O
+5	O
+,	O
+8	O
+.	O
+6	O
+and	O
+7	O
+.	O
+5	O
+%	O
+,	O
+respectively	O
+.	O
+in	O
+chronic	O
+liver	O
+diseases	O
+with	O
+a	O
+history	O
+of	O
+jaundice	O
+and	O
+/	O
+or	O
+hepatitis	O
+,	O
+previous	O
+transfusions	O
+are	O
+more	O
+frequently	O
+associated	O
+with	O
+type	O
+NANB	O
+than	O
+with	O
+type	O
+B	O
+disease	O
+.	O
+
+Of	O
+115	O
+hepatitis	O
+B	O
+patients	O
+seen	O
+at	O
+12	O
+months	O
+,	O
+6	O
+%	O
+had	O
+chronic	O
+hepatitis	O
+Bs	O
+antigenaemia	O
+,	O
+60	O
+%	O
+had	O
+developed	O
+anti	B-GENE
+-	I-GENE
+HBs	I-GENE
+antibodies	I-GENE
+,	O
+and	O
+7	O
+.	O
+3	O
+%	O
+still	O
+had	O
+abnormal	O
+liver	O
+function	O
+.	O
+
+Survey	O
+on	O
+antibody	O
+against	O
+egg	O
+drop	O
+syndrome	O
+-	O
+1976	O
+virus	O
+among	O
+chicken	O
+flocks	O
+in	O
+Japan	O
+.	O
+
+In	O
+49	O
+patients	O
+in	O
+whom	O
+gated	O
+equilibrium	O
+ventriculography	O
+and	O
+cardiac	O
+catheterization	O
+were	O
+performed	O
+within	O
+a	O
+6	O
+day	O
+interval	O
+,	O
+total	O
+and	O
+fractional	O
+portions	O
+of	O
+global	O
+and	O
+regional	O
+right	O
+ventricular	O
+ejection	O
+fraction	O
+(	O
+RVEF	O
+)	O
+were	O
+correlated	O
+with	O
+pulmonary	O
+arterial	O
+systolic	O
+pressure	O
+.	O
+
+74	O
+,	O
+193	O
+-	O
+197	O
+)	O
+.	O
+
+The	O
+combination	O
+of	O
+MISO	O
+and	O
+WR	O
+-	O
+2721	O
+gave	O
+an	O
+intermediate	O
+response	O
+compared	O
+with	O
+either	O
+drug	O
+used	O
+alone	O
+,	O
+resulting	O
+in	O
+some	O
+sensitization	O
+with	O
+single	O
+doses	O
+and	O
+an	O
+overall	O
+protection	O
+with	O
+repeated	O
+small	O
+doses	O
+.	O
+
+Two	O
+mutations	O
+that	O
+affect	O
+larval	B-GENE
+cuticle	I-GENE
+protein	I-GENE
+gene	I-GENE
+expression	O
+in	O
+the	O
+2	O
+/	O
+3	O
+variant	O
+Drosophila	O
+melanogaster	O
+strain	O
+were	O
+investigated	O
+.	O
+
+A	O
+cDNA	O
+cloning	O
+vector	O
+that	O
+permits	O
+expression	O
+of	O
+cDNA	O
+inserts	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Hybridization	O
+of	O
+plasmid	O
+-	O
+transformed	O
+Escherichia	O
+coli	O
+RR1	O
+colonies	O
+with	O
+32P	O
+-	O
+labeled	O
+viral	O
+genome	O
+RNAs	O
+demonstrated	O
+the	O
+presence	O
+of	O
+DNA	O
+clones	O
+representative	O
+of	O
+each	O
+of	O
+the	O
+10	O
+reovirus	O
+RNAs	O
+and	O
+10	O
+of	O
+the	O
+11	O
+constituent	O
+segments	O
+of	O
+the	O
+rotavirus	O
+genome	O
+.	O
+
+Another	O
+sequence	O
+,	O
+GGGXGGAG	O
+,	O
+which	O
+is	O
+repeated	O
+several	O
+times	O
+in	O
+many	O
+polyomaviruses	O
+and	O
+adenoviruses	O
+,	O
+and	O
+which	O
+is	O
+thought	O
+to	O
+play	O
+a	O
+role	O
+in	O
+DNA	O
+replication	O
+and	O
+/	O
+or	O
+transcription	O
+,	O
+is	O
+not	O
+found	O
+in	O
+the	O
+JCV	O
+sequence	O
+presented	O
+.	O
+
+Lung	O
+density	O
+increased	O
+in	O
+quartz	O
+-	O
+exposed	O
+,	O
+but	O
+not	O
+in	O
+volcanic	O
+-	O
+ash	O
+-	O
+exposed	O
+animals	O
+.	O
+
+The	O
+hepatitis	B-GENE
+A	I-GENE
+virus	I-GENE
+antibody	I-GENE
+(	O
+anti	B-GENE
+-	I-GENE
+HAV	I-GENE
+)	O
+in	O
+chronic	O
+diffuse	O
+liver	O
+diseases	O
+
+The	O
+junctions	O
+between	O
+viral	O
+and	O
+cellular	O
+sequences	O
+were	O
+determined	O
+by	O
+DNA	O
+sequence	O
+analysis	O
+to	O
+be	O
+517	O
+nucleotides	O
+into	O
+the	O
+p30	B-GENE
+sequence	I-GENE
+and	O
+1	O
+,	O
+920	O
+nucleotides	O
+into	O
+the	O
+polymerase	O
+sequence	O
+.	O
+
+Naloxone	O
+(	O
+2	O
+mg	O
+/	O
+kg	O
+bolus	O
++	O
+2	O
+mg	O
+X	O
+kg	O
+-	O
+1	O
+X	O
+h	O
+-	O
+1	O
+)	O
+was	O
+given	O
+with	O
+one	O
+of	O
+the	O
+two	O
+doses	O
+of	O
+the	O
+lipopolysaccharide	O
+.	O
+
+I	O
+.	O
+
+Viral	O
+RNA	O
+,	O
+molecularly	O
+cloned	O
+proviral	O
+DNA	O
+,	O
+and	O
+virus	O
+-	O
+specific	O
+protein	O
+of	O
+avian	O
+retrovirus	O
+MH2	O
+were	O
+analyzed	O
+.	O
+
+Intracellular	O
+recordings	O
+were	O
+performed	O
+on	O
+the	O
+optic	O
+tectum	O
+of	O
+the	O
+carp	O
+in	O
+vitro	O
+.	O
+
+Molecular	O
+structure	O
+and	O
+evolutionary	O
+origin	O
+of	O
+human	B-GENE
+cardiac	I-GENE
+muscle	I-GENE
+actin	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+mutants	O
+were	O
+obtained	O
+by	O
+substitution	O
+into	O
+a	O
+molecular	O
+clone	O
+of	O
+M	O
+-	O
+MuLV	O
+DNA	O
+by	O
+DNA	O
+from	O
+two	O
+acutely	O
+transforming	O
+viruses	O
+,	O
+Ableson	O
+MuLV	O
+(	O
+Ab	O
+-	O
+MuLV	O
+)	O
+and	O
+Moloney	O
+murine	O
+sarcoma	O
+virus	O
+(	O
+M	O
+-	O
+MSV	O
+)	O
+.	O
+
+Plasmids	O
+for	O
+the	O
+cloning	O
+and	O
+expression	O
+of	O
+full	O
+-	O
+length	O
+double	O
+-	O
+stranded	O
+cDNAs	O
+under	O
+control	O
+of	O
+the	O
+SV40	B-GENE
+early	I-GENE
+or	O
+late	B-GENE
+gene	I-GENE
+promoter	O
+.	O
+
+Supplementing	O
+a	O
+soybean	O
+protein	O
+and	O
+sucrose	O
+-	O
+based	O
+diet	O
+with	O
+levels	O
+of	O
+2	O
+.	O
+2	O
+,	O
+11	O
+,	O
+and	O
+55	O
+ppm	O
+of	O
+the	O
+antibiotic	O
+,	O
+from	O
+the	O
+two	O
+sources	O
+each	O
+with	O
+two	O
+different	O
+purities	O
+,	O
+improved	O
+weight	O
+gain	O
+of	O
+chicks	O
+an	O
+average	O
+of	O
+23	O
+%	O
+and	O
+improved	O
+feed	O
+efficiency	O
+an	O
+average	O
+of	O
+13	O
+%	O
+at	O
+the	O
+higher	O
+levels	O
+(	O
+all	O
+P	O
+less	O
+than	O
+.	O
+01	O
+)	O
+.	O
+
+Overall	O
+prevalences	O
+of	O
+antibody	O
+were	O
+70	O
+per	O
+cent	O
+in	O
+cattle	O
+,	O
+67	O
+per	O
+cent	O
+in	O
+sheep	O
+and	O
+76	O
+per	O
+cent	O
+in	O
+goats	O
+as	O
+assessed	O
+by	O
+an	O
+immunodiffusion	O
+test	O
+.	O
+
+Expression	O
+of	O
+herpes	O
+simplex	O
+virus	O
+beta	O
+and	O
+gamma	O
+genes	O
+integrated	O
+in	O
+mammalian	O
+cells	O
+and	O
+their	O
+induction	O
+by	O
+an	O
+alpha	O
+gene	O
+product	O
+.	O
+
+The	O
+splice	O
+acceptor	O
+site	O
+is	O
+ca	O
+.	O
+
+This	O
+is	O
+consistent	O
+with	O
+a	O
+model	O
+proposing	O
+that	O
+SSV	O
+was	O
+generated	O
+by	O
+recombination	O
+between	O
+proviral	O
+DNA	O
+of	O
+a	O
+simian	O
+sarcoma	O
+associated	O
+virus	O
+and	O
+proto	B-GENE
+-	I-GENE
+sis	I-GENE
+and	O
+that	O
+introns	O
+were	O
+spliced	O
+out	O
+subsequently	O
+from	O
+a	O
+fused	O
+viral	B-GENE
+-	I-GENE
+sis	I-GENE
+messenger	I-GENE
+RNA	I-GENE
+.	O
+
+We	O
+conclude	O
+that	O
+,	O
+with	O
+autonomic	O
+nervous	O
+system	O
+activity	O
+intact	O
+,	O
+carotid	O
+chemoreceptor	O
+reflex	O
+activation	O
+can	O
+elicit	O
+an	O
+absolute	O
+reflexly	O
+mediated	O
+reduction	O
+in	O
+coronary	O
+blood	O
+flow	O
+in	O
+the	O
+normal	O
+,	O
+conscious	O
+dog	O
+,	O
+despite	O
+an	O
+increase	O
+in	O
+arterial	O
+pressure	O
+.	O
+
+Female	O
+subjects	O
+,	O
+including	O
+both	O
+normal	O
+subjects	O
+and	O
+idiopathic	O
+calcium	O
+stone	O
+-	O
+formers	O
+,	O
+have	O
+higher	O
+urinary	O
+cyclic	O
+AMP	O
+levels	O
+than	O
+their	O
+male	O
+counterparts	O
+,	O
+and	O
+this	O
+difference	O
+is	O
+significant	O
+when	O
+urinary	O
+cyclic	O
+AMP	O
+is	O
+expressed	O
+in	O
+the	O
+units	O
+mumol	O
+/	O
+g	O
+of	O
+creatinine	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+'	O
+morning	O
+dip	O
+'	O
+observed	O
+in	O
+asthmatic	O
+patients	O
+cannot	O
+simply	O
+be	O
+explained	O
+by	O
+changes	O
+in	O
+cell	O
+receptor	O
+number	O
+or	O
+affinity	O
+,	O
+as	O
+our	O
+results	O
+suggest	O
+that	O
+both	O
+groups	O
+have	O
+intact	O
+beta	B-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+function	O
+.	O
+
+The	O
+effect	O
+of	O
+desipramine	O
+probably	O
+represents	O
+inhibition	O
+of	O
+neuronal	O
+uptake	O
+and	O
+that	O
+of	O
+amitriptyline	O
+and	O
+mianserin	O
+blockade	O
+of	O
+neuronal	O
+uptake	O
+and	O
+prejunctional	O
+alpha	B-GENE
+2	I-GENE
+-	I-GENE
+adrenoreceptors	I-GENE
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+gp54	B-GENE
+structural	I-GENE
+gene	I-GENE
+is	O
+required	O
+for	O
+initiation	O
+or	O
+amplification	O
+of	O
+the	O
+splenic	O
+erythroblast	O
+hyperplasia	O
+which	O
+characterizes	O
+the	O
+preleukemic	O
+phase	O
+of	O
+Rauscher	O
+disease	O
+.	O
+
+Surgical	O
+treatment	O
+of	O
+pulmonary	O
+metastases	O
+.	O
+
+A	O
+promoter	O
+sequence	O
+(	O
+Goldberg	O
+-	O
+Hogness	O
+or	O
+TATA	O
+box	O
+)	O
+is	O
+situated	O
+28	O
+base	O
+pairs	O
+upstream	O
+from	O
+the	O
+point	O
+of	O
+initiation	O
+of	O
+transcription	O
+which	O
+was	O
+found	O
+by	O
+S1	B-GENE
+nuclease	I-GENE
+mapping	O
+and	O
+by	O
+oligonucleotide	O
+-	O
+primed	O
+reverse	O
+transcription	O
+of	O
+rat	B-GENE
+PTH	I-GENE
+mRNA	I-GENE
+.	O
+
+Each	O
+of	O
+these	O
+spliced	O
+mRNAs	O
+has	O
+an	O
+untranslated	O
+leader	O
+sequence	O
+of	O
+249	O
+bases	O
+and	O
+a	O
+single	O
+intron	O
+of	O
+approximately	O
+540	O
+bases	O
+which	O
+are	O
+contained	O
+entirely	O
+within	O
+TRs	O
+/	O
+IRs	O
+sequences	O
+.	O
+
+The	O
+expression	O
+of	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+was	O
+detected	O
+within	O
+1	O
+h	O
+after	O
+infection	O
+of	O
+cells	O
+with	O
+recombinant	O
+virus	O
+,	O
+reflecting	O
+the	O
+early	O
+nature	O
+of	O
+the	O
+promoters	O
+used	O
+.	O
+
+NPT	B-GENE
+II	I-GENE
+synthesis	O
+,	O
+measured	O
+by	O
+agar	O
+plate	O
+assays	O
+of	O
+kanamycin	O
+resistance	O
+and	O
+by	O
+immunoprecipitation	O
+of	O
+the	O
+NPT	B-GENE
+II	I-GENE
+protein	I-GENE
+,	O
+was	O
+repressed	O
+in	O
+the	O
+presence	O
+of	O
+cysteine	O
+and	O
+derepressed	O
+in	O
+its	O
+absence	O
+.	O
+
+A	O
+computed	O
+tomographic	O
+scan	O
+obtained	O
+after	O
+EOE	O
+-	O
+13	O
+infusion	O
+accurately	O
+showed	O
+the	O
+perfusion	O
+pattern	O
+of	O
+the	O
+implanted	O
+catheter	O
+.	O
+
+The	O
+12	B-GENE
+,	I-GENE
+000	I-GENE
+MW	I-GENE
+(	I-GENE
+12K	I-GENE
+)	I-GENE
+IE	I-GENE
+polypeptide	I-GENE
+encoded	O
+by	O
+IEmRNA	B-GENE
+-	I-GENE
+5	I-GENE
+is	O
+translated	O
+from	O
+an	O
+88	O
+codon	O
+open	O
+reading	O
+frame	O
+,	O
+leaving	O
+a	O
+1200	O
+base	O
+3	O
+'	O
+non	O
+-	O
+translated	O
+region	O
+.	O
+
+The	O
+greatest	O
+difference	O
+between	O
+the	O
+Ad7	B-GENE
+and	I-GENE
+Ad5	I-GENE
+DBPs	I-GENE
+is	O
+the	O
+absence	O
+,	O
+in	O
+the	O
+Ad7	O
+protein	O
+,	O
+of	O
+12	O
+amino	O
+acids	O
+located	O
+between	O
+the	O
+two	O
+functional	O
+domains	O
+in	O
+the	O
+Ad5	O
+protein	O
+(	O
+amino	O
+acids	O
+151	O
+-	O
+162	O
+)	O
+.	O
+
+No	O
+significant	O
+correlation	O
+was	O
+found	O
+between	O
+LVM	O
+or	O
+wall	O
+thickness	O
+and	O
+body	O
+surface	O
+area	O
+,	O
+age	O
+,	O
+blood	O
+pressure	O
+,	O
+heart	O
+rate	O
+,	O
+cardiac	O
+output	O
+,	O
+total	O
+peripheral	O
+resistance	O
+and	O
+left	O
+ventricular	O
+systolic	O
+wall	O
+stress	O
+,	O
+whereas	O
+CD25	O
+was	O
+correlated	O
+with	O
+urinary	O
+catecholamines	O
+only	O
+in	O
+hypertensive	O
+patients	O
+(	O
+r	O
+=	O
+0	O
+.	O
+606	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+no	O
+Shine	O
+-	O
+Dalgarno	O
+sequences	O
+are	O
+present	O
+upstream	O
+of	O
+the	O
+presumed	O
+translational	O
+start	O
+codons	O
+.	O
+
+The	O
+gene	B-GENE
+cat	I-GENE
+-	I-GENE
+86	I-GENE
+,	O
+specifying	O
+chloramphenicol	B-GENE
+-	I-GENE
+inducible	I-GENE
+chloramphenicol	I-GENE
+acetyltransferase	I-GENE
+,	O
+is	O
+located	O
+on	O
+the	O
+1	O
+.	O
+1	O
+-	O
+kilobase	O
+cloned	O
+DNA	O
+.	O
+
+The	O
+myeloproliferative	O
+sarcoma	O
+virus	O
+(	O
+MPSV	O
+)	O
+was	O
+derived	O
+by	O
+passage	O
+of	O
+Moloney	O
+sarcoma	O
+virus	O
+(	O
+Mo	O
+-	O
+MuSV	O
+)	O
+in	O
+adult	O
+mice	O
+.	O
+
+The	O
+same	O
+-	O
+sized	O
+EBNA	B-GENE
+protein	I-GENE
+(	I-GENE
+approximately	I-GENE
+78	I-GENE
+,	I-GENE
+000	I-GENE
+)	I-GENE
+was	O
+made	O
+after	O
+transfection	O
+with	O
+BamHI	B-GENE
+-	I-GENE
+K	I-GENE
+(	I-GENE
+5	I-GENE
+.	I-GENE
+2	I-GENE
+kilobase	I-GENE
+pairs	I-GENE
+[	I-GENE
+kbp	I-GENE
+]	I-GENE
+)	I-GENE
+or	O
+the	O
+I1f	O
+subfragment	O
+(	O
+2	O
+.	O
+9	O
+kbp	O
+)	O
+.	O
+
+They	O
+generated	O
+ca	O
+.	O
+
+Here	O
+we	O
+have	O
+determined	O
+the	O
+nucleotide	O
+sequence	O
+of	O
+3	O
+.	O
+5	O
+kb	O
+from	O
+the	O
+3	O
+'	O
+end	O
+of	O
+delta	B-GENE
+gag	I-GENE
+to	O
+the	O
+3	O
+'	O
+end	O
+of	O
+molecularly	O
+cloned	O
+proviral	O
+MH2	O
+DNA	O
+,	O
+in	O
+order	O
+to	O
+elucidate	O
+the	O
+genetic	O
+structure	O
+of	O
+the	O
+virus	O
+and	O
+to	O
+compare	O
+it	O
+with	O
+other	O
+mht	B-GENE
+-	O
+and	O
+myc	B-GENE
+-	O
+containing	O
+oncogenic	O
+viruses	O
+as	O
+well	O
+as	O
+with	O
+the	O
+chicken	B-GENE
+proto	I-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+.	O
+
+USA	O
+80	O
+,	O
+802	O
+-	O
+806	O
+]	O
+was	O
+used	O
+to	O
+isolate	O
+a	O
+genomic	O
+clone	O
+lambda	O
+PGK	B-GENE
+-	I-GENE
+1	I-GENE
+containing	O
+a	O
+portion	O
+of	O
+an	O
+autosomal	O
+locus	O
+for	O
+phosphoglycerate	B-GENE
+kinase	I-GENE
+(	O
+PGK	B-GENE
+)	O
+.	O
+
+A	O
+.	O
+
+188	O
+patients	O
+received	O
+cimetidine	O
+400	O
+mg	O
+q	O
+.	O
+i	O
+.	O
+d	O
+.	O
+intravenously	O
+and	O
+1	O
+,	O
+000	O
+mg	O
+daily	O
+orally	O
+in	O
+divided	O
+doses	O
+.	O
+
+An	O
+immunologic	O
+test	O
+using	O
+stomach	O
+and	O
+tumor	O
+antigens	O
+for	O
+screening	O
+of	O
+those	O
+at	O
+high	O
+risk	O
+for	O
+stomach	O
+cancer	O
+is	O
+suggested	O
+.	O
+
+Thirty	O
+isolates	O
+of	O
+Haemophilus	O
+influenzae	O
+type	O
+b	O
+were	O
+obtained	O
+during	O
+an	O
+outbreak	O
+of	O
+invasive	O
+H	O
+.	O
+influenzae	O
+type	O
+b	O
+disease	O
+and	O
+were	O
+classified	O
+by	O
+the	O
+electrophoretic	O
+profile	O
+of	O
+their	O
+lipopolysaccharide	O
+(	O
+LPS	O
+)	O
+.	O
+
+Tiaprofenic	O
+acid	O
+overdose	O
+.	O
+
+Frog	O
+type	O
+I	O
+(	O
+Ft	O
+I	O
+)	O
+and	O
+frog	O
+type	O
+II	O
+(	O
+Ft	O
+II	O
+)	O
+slowly	O
+adapting	O
+(	O
+SA	O
+)	O
+units	O
+produced	O
+spikes	O
+only	O
+at	O
+the	O
+indentation	O
+phase	O
+,	O
+and	O
+the	O
+threshold	O
+response	O
+phase	O
+(	O
+TRP	O
+)	O
+,	O
+i	O
+.	O
+e	O
+.	O
+.	O
+the	O
+phase	O
+of	O
+the	O
+first	O
+spike	O
+was	O
+for	O
+ca	O
+.	O
+
+Frog	O
+type	O
+I	O
+(	O
+Ft	O
+I	O
+)	O
+and	O
+frog	O
+type	O
+II	O
+(	O
+Ft	O
+II	O
+)	O
+slowly	O
+adapting	O
+(	O
+SA	O
+)	O
+units	O
+produced	O
+spikes	O
+only	O
+at	O
+the	O
+indentation	O
+phase	O
+,	O
+and	O
+the	O
+threshold	O
+response	O
+phase	O
+(	O
+TRP	O
+)	O
+,	O
+i	O
+.	O
+e	O
+.	O
+.	O
+the	O
+phase	O
+of	O
+the	O
+first	O
+spike	O
+was	O
+for	O
+ca	O
+.	O
+
+DMCM	O
+also	O
+permits	O
+extension	O
+of	O
+the	O
+possibilities	O
+of	O
+obtaining	O
+and	O
+transplanting	O
+donor	O
+organs	O
+.	O
+
+Grimelius	O
+stain	O
+was	O
+positive	O
+,	O
+Masson	O
+Fontana	O
+stain	O
+negative	O
+.	O
+
+Blood	O
+glucose	O
+and	O
+plasma	O
+insulin	B-GENE
+were	O
+measured	O
+at	O
+zero	O
+time	O
+and	O
+then	O
+at	O
+15	O
+,	O
+30	O
+,	O
+60	O
+,	O
+90	O
+and	O
+120	O
+min	O
+after	O
+ingestion	O
+of	O
+25	O
+g	O
+glucose	O
+,	O
+fructose	O
+or	O
+lactose	O
+,	O
+or	O
+30	O
+g	O
+honey	O
+,	O
+50	O
+g	O
+white	O
+bread	O
+,	O
+125	O
+g	O
+white	O
+rice	O
+or	O
+potatoes	O
+,	O
+150	O
+g	O
+apples	O
+or	O
+260	O
+g	O
+carrots	O
+.	O
+
+Clinical	O
+use	O
+of	O
+absorbable	O
+polyglycolic	O
+acid	O
+suture	O
+in	O
+Blalock	O
+-	O
+Taussig	O
+'	O
+s	O
+operation	O
+
+Among	O
+these	O
+are	O
+:	O
+(	O
+1	O
+)	O
+Is	O
+there	O
+sufficient	O
+understanding	O
+of	O
+family	O
+pathophysiology	O
+,	O
+of	O
+the	O
+sensitivity	O
+and	O
+specificity	O
+of	O
+diagnostic	O
+techniques	O
+and	O
+of	O
+the	O
+safety	O
+and	O
+efficacy	O
+of	O
+therapeutic	O
+modalities	O
+to	O
+make	O
+true	O
+family	O
+health	O
+care	O
+possible	O
+?	O
+(	O
+2	O
+)	O
+If	O
+this	O
+type	O
+of	O
+care	O
+is	O
+possible	O
+,	O
+how	O
+are	O
+the	O
+needs	O
+of	O
+the	O
+family	O
+and	O
+its	O
+individual	O
+members	O
+met	O
+,	O
+or	O
+value	O
+judgements	O
+made	O
+about	O
+their	O
+relative	O
+importance	O
+?	O
+and	O
+(	O
+3	O
+)	O
+What	O
+are	O
+the	O
+consequences	O
+for	O
+the	O
+health	O
+care	O
+delivery	O
+system	O
+of	O
+this	O
+type	O
+of	O
+care	O
+?	O
+An	O
+extensive	O
+literature	O
+review	O
+is	O
+used	O
+in	O
+an	O
+attempt	O
+to	O
+answer	O
+these	O
+queries	O
+,	O
+from	O
+which	O
+questions	O
+for	O
+further	O
+study	O
+are	O
+posed	O
+.	O
+
+In	O
+patients	O
+in	O
+group	O
+A	O
+(	O
+"	O
+normal	O
+"	O
+CI	O
+)	O
+,	O
+the	O
+CI	O
+,	O
+heart	O
+rate	O
+and	O
+the	O
+mean	O
+circumferential	O
+fiber	O
+shortening	O
+velocity	O
+(	O
+mVCF	O
+)	O
+were	O
+normal	O
+,	O
+but	O
+the	O
+TPR	O
+was	O
+increased	O
+significantly	O
+.	O
+
+Immunologically	O
+reactive	O
+insulin	B-GENE
+levels	O
+were	O
+determined	O
+in	O
+freely	O
+-	O
+moving	O
+normal	O
+rats	O
+offered	O
+three	O
+different	O
+test	O
+-	O
+meals	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+both	O
+naturally	O
+acquired	O
+and	O
+passive	O
+(	O
+modified	O
+immune	B-GENE
+serum	I-GENE
+globulin	I-GENE
+)	O
+antibodies	O
+to	O
+type	B-GENE
+III	I-GENE
+group	I-GENE
+B	I-GENE
+Streptococcus	I-GENE
+antigen	I-GENE
+are	O
+partially	O
+protective	O
+against	O
+intra	O
+-	O
+amniotic	O
+infection	O
+.	O
+
+In	O
+the	O
+posthospital	O
+phase	O
+of	O
+AMI	O
+,	O
+as	O
+well	O
+as	O
+in	O
+CCHD	O
+,	O
+the	O
+occurrence	O
+of	O
+high	O
+-	O
+grade	O
+VPBs	O
+usually	O
+indicates	O
+more	O
+advanced	O
+degrees	O
+of	O
+both	O
+coronary	O
+and	O
+left	O
+ventricular	O
+disease	O
+as	O
+well	O
+as	O
+the	O
+possibility	O
+of	O
+cardiac	O
+and	O
+/	O
+or	O
+sudden	O
+death	O
+.	O
+
+The	O
+genes	O
+at	O
+each	O
+locus	O
+are	O
+divergently	O
+transcribed	O
+and	O
+the	O
+coding	O
+sequences	O
+are	O
+separated	O
+by	O
+646	O
+base	O
+-	O
+pairs	O
+at	O
+one	O
+locus	O
+and	O
+676	O
+base	O
+-	O
+pairs	O
+at	O
+the	O
+other	O
+.	O
+
+The	O
+enzymic	O
+hydrolysis	O
+of	O
+urea	O
+produces	O
+ammonia	O
+which	O
+causes	O
+a	O
+vivid	O
+yellow	O
+to	O
+purple	O
+colour	O
+change	O
+in	O
+the	O
+pH	O
+indicator	O
+.	O
+
+The	O
+clinical	O
+efficacy	O
+rates	O
+evaluated	O
+in	O
+151	O
+cases	O
+(	O
+KS	O
+-	O
+R1	O
+group	O
+in	O
+77	O
+cases	O
+,	O
+oral	O
+group	O
+in	O
+74	O
+cases	O
+)	O
+on	O
+standard	O
+criteria	O
+of	O
+committee	O
+members	O
+were	O
+88	O
+.	O
+3	O
+%	O
+for	O
+the	O
+KS	O
+-	O
+R1	O
+group	O
+and	O
+86	O
+.	O
+5	O
+%	O
+for	O
+the	O
+oral	O
+group	O
+,	O
+respectively	O
+.	O
+
+Side	O
+effect	O
+including	O
+subjective	O
+and	O
+objective	O
+symptoms	O
+were	O
+strictly	O
+evaluated	O
+in	O
+163	O
+cases	O
+(	O
+KS	O
+-	O
+R1	O
+group	O
+in	O
+83	O
+cases	O
+,	O
+oral	O
+group	O
+in	O
+80	O
+cases	O
+)	O
+,	O
+but	O
+the	O
+incidence	O
+rate	O
+which	O
+was	O
+22	O
+.	O
+9	O
+%	O
+for	O
+the	O
+KS	O
+-	O
+R1	O
+group	O
+and	O
+23	O
+.	O
+8	O
+%	O
+for	O
+the	O
+oral	O
+group	O
+showed	O
+no	O
+significant	O
+difference	O
+.	O
+
+Plasma	O
+renin	B-GENE
+activity	O
+did	O
+not	O
+change	O
+in	O
+response	O
+to	O
+head	O
+-	O
+up	O
+tilt	O
+or	O
+isoprenaline	O
+infusion	O
+in	O
+the	O
+patients	O
+.	O
+
+Martin	O
+Luther	O
+and	O
+his	O
+physicians	O
+.	O
+
+Enhancement	O
+of	O
+the	O
+immune	O
+response	O
+by	O
+aspecific	O
+action	O
+of	O
+vaccine	O
+additives	O
+in	O
+the	O
+aerogenic	O
+immunization	O
+of	O
+swine	O
+against	O
+swine	O
+plague	O
+
+Induced	O
+gamma	O
+-	O
+ray	O
+spectroscopy	O
+
+Analysis	O
+of	O
+proteins	O
+synthesized	O
+by	O
+plasmids	O
+containing	O
+deleted	O
+forms	O
+of	O
+the	O
+trfA	B-GENE
+region	I-GENE
+indicates	O
+that	O
+the	O
+A2	B-GENE
+protein	I-GENE
+is	O
+the	O
+essential	O
+trfA	B-GENE
+-	I-GENE
+encoded	I-GENE
+replication	I-GENE
+protein	I-GENE
+of	O
+plasmid	O
+RK2	O
+.	O
+
+Effects	O
+of	O
+negative	O
+pleural	O
+pressure	O
+on	O
+left	O
+ventricular	O
+hemodynamics	O
+.	O
+
+Resting	O
+plasma	O
+norepinephrine	O
+(	O
+NE	O
+)	O
+and	O
+epinephrine	O
+(	O
+E	O
+)	O
+levels	O
+were	O
+lower	O
+during	O
+active	O
+therapy	O
+than	O
+2	O
+wk	O
+after	O
+withdrawal	O
+(	O
+guanfacine	O
+and	O
+control	O
+:	O
+plasma	O
+NE	O
+,	O
+0	O
+.	O
+27	O
++	O
+/	O
+-	O
+0	O
+.	O
+03	O
+/	O
+0	O
+.	O
+64	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+ng	O
+/	O
+ml	O
+;	O
+plasma	O
+E	O
+,	O
+0	O
+.	O
+09	O
++	O
+/	O
+-	O
+0	O
+.	O
+02	O
+/	O
+0	O
+.	O
+17	O
++	O
+/	O
+-	O
+0	O
+.	O
+05	O
+ng	O
+/	O
+ml	O
+)	O
+.	O
+
+Renal	O
+response	O
+to	O
+captopril	O
+in	O
+severe	O
+heart	O
+failure	O
+:	O
+role	O
+of	O
+furosemide	O
+in	O
+natriuresis	O
+and	O
+reversal	O
+of	O
+hyponatremia	O
+.	O
+
+Lauciello	O
+describes	O
+a	O
+technique	O
+for	O
+the	O
+placement	O
+of	O
+functionally	O
+generated	O
+amalgam	O
+stops	O
+as	O
+restorations	O
+within	O
+mandibular	O
+acrylic	O
+teeth	O
+.	O
+
+Eleven	O
+biopsy	O
+specimens	O
+(	O
+five	O
+papules	O
+and	O
+six	O
+dusky	O
+or	O
+crusted	O
+lesions	O
+)	O
+from	O
+four	O
+patients	O
+with	O
+pityriasis	O
+lichenoides	O
+et	O
+varioliformis	O
+acuta	O
+(	O
+PLEVA	O
+)	O
+were	O
+studied	O
+by	O
+direct	O
+immunofluorescence	O
+and	O
+immunoperoxidase	B-GENE
+technics	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+a	O
+major	O
+part	O
+of	O
+the	O
+reduction	O
+in	O
+food	O
+intake	O
+in	O
+hyperphagic	O
+rats	O
+eating	O
+a	O
+quinine	O
+-	O
+adulterated	O
+diet	O
+is	O
+due	O
+to	O
+postingestional	O
+events	O
+.	O
+
+The	O
+aspirate	O
+from	O
+a	O
+parathyroid	O
+cyst	O
+was	O
+watery	O
+clear	O
+and	O
+contained	O
+high	O
+amount	O
+of	O
+parathyroid	B-GENE
+hormone	I-GENE
+.	O
+
+EGV	O
+had	O
+no	O
+detectable	O
+effect	O
+on	O
+PP	B-GENE
+secretion	O
+under	O
+basal	O
+or	O
+stimulated	O
+conditions	O
+.	O
+
+The	O
+numerous	O
+tests	O
+demonstrate	O
+that	O
+the	O
+HDL	O
+-	O
+2M	O
+can	O
+be	O
+extensively	O
+and	O
+successfully	O
+used	O
+for	O
+therapy	O
+of	O
+insulin	B-GENE
+-	O
+dependent	O
+diabetes	O
+mellitus	O
+in	O
+clinical	O
+practice	O
+.	O
+
+Lung	O
+prostacyclin	O
+production	O
+may	O
+be	O
+related	O
+to	O
+flow	O
+.	O
+
+For	O
+the	O
+first	O
+30	O
+min	O
+following	O
+insulin	B-GENE
+administration	O
+,	O
+the	O
+rate	O
+of	O
+change	O
+in	O
+glucose	O
+levels	O
+was	O
+significantly	O
+less	O
+among	O
+the	O
+patients	O
+with	O
+major	O
+depressive	O
+disorder	O
+than	O
+among	O
+either	O
+the	O
+patients	O
+with	O
+dysthymic	O
+disorder	O
+or	O
+the	O
+normal	O
+control	O
+subjects	O
+.	O
+
+Management	O
+of	O
+hypertension	O
+in	O
+the	O
+elderly	O
+.	O
+
+Transplantation	O
+of	O
+kidneys	O
+of	O
+juvenile	O
+donors	O
+in	O
+adult	O
+recipients	O
+.	O
+
+Ten	O
+patients	O
+with	O
+advanced	O
+,	O
+diffuse	O
+Hodgkin	O
+'	O
+s	O
+and	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphomas	O
+responding	O
+poorly	O
+to	O
+the	O
+most	O
+widely	O
+employed	O
+primary	O
+chemotherapy	O
+regimens	O
+were	O
+treated	O
+with	O
+a	O
+high	O
+-	O
+dose	O
+chemotherapy	O
+(	O
+HDC	O
+)	O
+followed	O
+by	O
+rescue	O
+with	O
+non	O
+-	O
+frozen	O
+autologous	O
+bone	O
+marrow	O
+infusion	O
+(	O
+ABMT	O
+)	O
+.	O
+
+Effect	O
+of	O
+proteolytic	O
+enzymes	O
+and	O
+polypeptides	O
+on	O
+the	O
+antacid	O
+activity	O
+of	O
+almagate	O
+and	O
+other	O
+antacids	O
+.	O
+
+Results	O
+of	O
+a	O
+controlled	O
+study	O
+
+Hydrallazine	O
+also	O
+caused	O
+a	O
+slight	O
+increase	O
+in	O
+plasma	B-GENE
+renin	I-GENE
+activity	O
+and	O
+urinary	O
+excretion	O
+of	O
+noradrenaline	O
+.	O
+
+Urease	B-GENE
+activity	O
+of	O
+97	O
+%	O
+of	O
+these	O
+organisms	O
+became	O
+evident	O
+within	O
+30	O
+min	O
+.	O
+
+After	O
+description	O
+of	O
+his	O
+short	O
+life	O
+and	O
+an	O
+explanation	O
+of	O
+the	O
+light	O
+conductor	O
+Bozzini	O
+'	O
+s	O
+merit	O
+is	O
+emphasized	O
+,	O
+by	O
+his	O
+invention	O
+as	O
+first	O
+physician	O
+to	O
+have	O
+made	O
+accessible	O
+to	O
+medicine	O
+endoscopic	O
+diagnostic	O
+possibilities	O
+.	O
+
+The	O
+effect	O
+of	O
+lithium	O
+on	O
+the	O
+osmoregulation	O
+of	O
+arginine	B-GENE
+vasopressin	I-GENE
+secretion	O
+.	O
+
+Antithrombin	B-GENE
+III	I-GENE
+(	O
+AT	B-GENE
+III	I-GENE
+)	O
+is	O
+a	O
+plasma	O
+protein	O
+which	O
+acts	O
+as	O
+the	O
+principal	O
+inhibitor	O
+of	O
+thrombin	B-GENE
+and	O
+is	O
+a	O
+major	O
+modulator	O
+of	O
+intravascular	O
+coagulation	O
+.	O
+
+Eighteen	O
+patients	O
+were	O
+untreated	O
+,	O
+and	O
+8	O
+had	O
+been	O
+given	O
+previous	O
+treatment	O
+with	O
+depot	O
+testosterone	O
+100	O
+mg	O
+intramuscularly	O
+every	O
+2	O
+-	O
+3	O
+weeks	O
+for	O
+an	O
+average	O
+duration	O
+of	O
+4	O
+.	O
+7	O
+years	O
+.	O
+
+195mPt	O
+-	O
+labeled	O
+cisplatin	O
+was	O
+administered	O
+iv	O
+and	O
+ip	O
+to	O
+control	O
+mice	O
+and	O
+to	O
+mice	O
+bearing	O
+Sarcoma	O
+180	O
+.	O
+
+New	O
+beta	O
+-	O
+blocking	O
+drugs	O
+have	O
+been	O
+introduced	O
+which	O
+may	O
+prove	O
+beneficial	O
+in	O
+certain	O
+clinical	O
+situations	O
+since	O
+they	O
+exert	O
+more	O
+selective	O
+blockade	O
+of	O
+the	O
+cardiac	B-GENE
+receptors	I-GENE
+(	O
+beta1	B-GENE
+)	O
+as	O
+opposed	O
+to	O
+smooth	B-GENE
+muscle	I-GENE
+receptors	I-GENE
+(	O
+beta2	B-GENE
+)	O
+.	O
+
+In	O
+the	O
+37	O
+patients	O
+without	O
+lung	O
+disease	O
+respiratory	O
+muscle	O
+weakness	O
+was	O
+accompanied	O
+by	O
+significant	O
+decreases	O
+in	O
+vital	O
+capacity	O
+,	O
+total	O
+lung	O
+capacity	O
+,	O
+and	O
+maximum	O
+voluntary	O
+ventilation	O
+;	O
+by	O
+significant	O
+increases	O
+in	O
+residual	O
+volume	O
+and	O
+arterial	O
+carbon	O
+dioxide	O
+tension	O
+(	O
+PaCO2	O
+)	O
+;	O
+and	O
+greater	O
+likelihood	O
+of	O
+dependence	O
+on	O
+ventilators	O
+,	O
+atelectasis	O
+,	O
+and	O
+pneumonia	O
+.	O
+
+Commun	O
+.	O
+
+Total	O
+cumulative	O
+doses	O
+of	O
+doxorubicin	O
+ranged	O
+from	O
+145	O
+to	O
+625	O
+mg	O
+.	O
+/	O
+m	O
+.	O
+2	O
+.	O
+
+Movement	O
+programming	O
+depends	O
+on	O
+understanding	O
+of	O
+behavioral	O
+requirements	O
+.	O
+
+Following	O
+20	O
+min	O
+of	O
+steady	O
+state	O
+anaesthesia	O
+during	O
+which	O
+measurements	O
+of	O
+IOP	O
+,	O
+arterial	O
+pressure	O
+,	O
+heart	O
+rate	O
+,	O
+FIO2	O
+,	O
+FE	O
+'	O
+CO2	O
+and	O
+CVP	O
+were	O
+recorded	O
+,	O
+one	O
+group	O
+of	O
+patients	O
+received	O
+atracurium	O
+0	O
+.	O
+45	O
+mg	O
+kg	O
+-	O
+1	O
+and	O
+the	O
+other	O
+pancuronium	O
+0	O
+.	O
+1	O
+mg	O
+kg	O
+-	O
+1	O
+.	O
+
+Gonadotropin	B-GENE
+levels	O
+in	O
+mothers	O
+who	O
+have	O
+had	O
+two	O
+sets	O
+of	O
+DZ	O
+twins	O
+.	O
+
+Freezing	O
+of	O
+plasma	O
+to	O
+obtain	O
+better	O
+yield	O
+of	O
+factor	B-GENE
+VIII	I-GENE
+:	O
+C	O
+.	O
+
+These	O
+children	O
+were	O
+grouped	O
+into	O
+four	O
+diagnostic	O
+categories	O
+:	O
+1	O
+)	O
+idiopathic	O
+GH	B-GENE
+deficiency	O
+(	O
+n	O
+=	O
+10	O
+)	O
+;	O
+2	O
+)	O
+organic	O
+hypopituitarism	O
+(	O
+n	O
+=	O
+7	O
+)	O
+;	O
+3	O
+)	O
+intrauterine	O
+growth	O
+retardation	O
+(	O
+n	O
+=	O
+5	O
+)	O
+;	O
+and	O
+4	O
+)	O
+constitutional	O
+delay	O
+of	O
+growth	O
+and	O
+/	O
+or	O
+familial	O
+short	O
+stature	O
+(	O
+n	O
+=	O
+18	O
+)	O
+,	O
+by	O
+standard	O
+clinical	O
+criteria	O
+and	O
+physiological	O
+and	O
+pharmacological	O
+tests	O
+of	O
+GH	B-GENE
+reserve	O
+.	O
+
+Each	O
+patient	O
+had	O
+measurable	O
+LH	B-GENE
+and	O
+FSH	B-GENE
+levels	O
+,	O
+with	O
+pulsed	O
+nocturnal	O
+secretion	O
+,	O
+and	O
+pubertal	O
+LH	B-GENE
+and	O
+FSH	B-GENE
+responses	O
+to	O
+LRH	B-GENE
+.	O
+
+These	O
+changes	O
+were	O
+the	O
+result	O
+of	O
+a	O
+decrease	O
+in	O
+afterload	O
+:	O
+mean	O
+aortic	O
+pressure	O
+fell	O
+from	O
+85	O
++	O
+/	O
+-	O
+11	O
+.	O
+8	O
+to	O
+68	O
++	O
+/	O
+-	O
+19	O
+.	O
+6	O
+mmHg	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+and	O
+systemic	O
+arterial	O
+resistance	O
+fell	O
+from	O
+2	O
+886	O
++	O
+/	O
+-	O
+745	O
+to	O
+2	O
+010	O
++	O
+/	O
+-	O
+610	O
+dynes	O
+/	O
+cm	O
+-	O
+5	O
+/	O
+sec	O
+/	O
+m	O
+-	O
+2	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Cimetidine	O
+800	O
+mg	O
+given	O
+at	O
+night	O
+is	O
+as	O
+effective	O
+as	O
+400	O
+mg	O
+twice	O
+daily	O
+;	O
+the	O
+single	O
+dose	O
+regimen	O
+may	O
+improve	O
+patient	O
+compliance	O
+,	O
+thus	O
+facilitating	O
+treatment	O
+.	O
+
+Ceftazidime	O
+shows	O
+promise	O
+as	O
+single	O
+-	O
+agent	O
+therapy	O
+for	O
+serious	O
+gram	O
+-	O
+negative	O
+bacillary	O
+infections	O
+.	O
+
+Regional	O
+CBF	O
+was	O
+determined	O
+by	O
+clearance	O
+of	O
+xenon	O
+133	O
+in	O
+67	O
+patients	O
+undergoing	O
+coronary	O
+bypass	O
+grafting	O
+procedures	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+serum	B-GENE
+BGP	I-GENE
+is	O
+a	O
+valuable	O
+measurement	O
+of	O
+bone	O
+metabolism	O
+.	O
+
+The	O
+management	O
+of	O
+the	O
+"	O
+chronic	O
+"	O
+patient	O
+.	O
+
+Study	O
+of	O
+bacterial	O
+motility	O
+and	O
+rate	O
+of	O
+movement	O
+using	O
+a	O
+closed	O
+circuit	O
+television	O
+
+Finding	O
+of	O
+Rhodnius	O
+prolixus	O
+Stal	O
+,	O
+1859	O
+,	O
+in	O
+babassu	O
+palm	O
+trees	O
+
+Each	O
+causative	O
+organism	O
+has	O
+a	O
+species	O
+-	O
+specific	O
+preference	O
+and	O
+requirement	O
+for	O
+temperature	O
+,	O
+salinity	O
+,	O
+pH	O
+,	O
+the	O
+basic	O
+nutrients	O
+,	O
+and	O
+growth	O
+factors	O
+,	O
+and	O
+the	O
+toxin	O
+formation	O
+is	O
+affected	O
+by	O
+these	O
+environmental	O
+factors	O
+.	O
+
+Deformities	O
+of	O
+the	O
+tip	O
+of	O
+the	O
+olecranon	O
+and	O
+of	O
+the	O
+coronoid	O
+process	O
+are	O
+also	O
+described	O
+(	O
+De	O
+Palma	O
+1956	O
+,	O
+Jordan	O
+1958	O
+,	O
+Ahlberg	O
+1965	O
+,	O
+Weseloh	O
+1973	O
+)	O
+.	O
+
+There	O
+was	O
+significant	O
+correlation	O
+of	O
+LVM	O
+/	O
+M2	O
+and	O
+PWVn	O
+for	O
+pre	O
+-	O
+AVR	O
+and	O
+post	O
+AVR	O
+studies	O
+.	O
+
+Statokinesimetric	O
+recording	O
+in	O
+Huntington	O
+choreas	O
+
+The	O
+development	O
+and	O
+histostructural	O
+organization	O
+of	O
+intrahepatic	O
+biliary	O
+ducts	O
+were	O
+studied	O
+on	O
+a	O
+human	O
+embryofetal	O
+material	O
+6	O
+to	O
+32	O
+weeks	O
+old	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+in	O
+an	O
+animal	O
+experiment	O
+that	O
+alterations	O
+of	O
+the	O
+renal	O
+vasculature	O
+and	O
+parenchyma	O
+after	O
+hemostasis	O
+performed	O
+by	O
+Infrared	O
+-	O
+Contact	O
+-	O
+Coagulation	O
+are	O
+best	O
+shown	O
+by	O
+intravital	O
+magnification	O
+angiography	O
+(	O
+magnification	O
+factor	O
+2	O
+.	O
+22	O
+)	O
+.	O
+
+Cardiovascular	O
+and	O
+adrenal	O
+medullo	O
+-	O
+sympathetic	O
+reactions	O
+to	O
+acute	O
+tobacco	O
+poisoning	O
+
+Intravenous	O
+injections	O
+of	O
+SG	O
+-	O
+75	O
+(	O
+0	O
+.	O
+03	O
+-	O
+1	O
+mg	O
+/	O
+kg	O
+)	O
+decreased	O
+systemic	O
+blood	O
+pressure	O
+(	O
+SBP	O
+)	O
+and	O
+increased	O
+peripheral	O
+(	O
+coronary	O
+,	O
+renal	O
+,	O
+mesenteric	O
+and	O
+femoral	O
+)	O
+blood	O
+flow	O
+(	O
+PBF	O
+)	O
+dose	O
+-	O
+dependently	O
+.	O
+
+In	O
+doses	O
+of	O
+0	O
+.	O
+03	O
+-	O
+0	O
+.	O
+3	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+,	O
+SG	O
+-	O
+75	O
+did	O
+not	O
+significantly	O
+affect	O
+pulse	O
+pressure	O
+,	O
+heart	O
+rate	O
+,	O
+aortic	O
+blood	O
+flow	O
+,	O
+left	O
+ventricular	O
+pressure	O
+(	O
+LVP	O
+)	O
+and	O
+LVdP	O
+/	O
+dt	O
+max	O
+.	O
+
+Resting	O
+VE	O
+in	O
+the	O
+luteal	O
+phase	O
+was	O
+7	O
+.	O
+8	O
+%	O
+greater	O
+than	O
+that	O
+in	O
+the	O
+follicular	O
+phase	O
+.	O
+
+Exposure	O
+of	O
+endothelium	O
+to	O
+pulsatile	O
+shear	O
+stresses	O
+that	O
+followed	O
+a	O
+tape	O
+recording	O
+of	O
+physiological	O
+flow	O
+waveforms	O
+(	O
+electromagnetic	O
+flowmeter	O
+)	O
+did	O
+not	O
+cause	O
+gross	O
+injury	O
+or	O
+denudation	O
+even	O
+when	O
+peak	O
+shear	O
+exceeded	O
+1500	O
+dyne	O
+/	O
+cm2	O
+.	O
+
+Modern	O
+cancer	O
+therapy	O
+has	O
+included	O
+surgery	O
+,	O
+radiotherapy	O
+,	O
+chemotherapy	O
+,	O
+and	O
+most	O
+recently	O
+,	O
+immunotherapy	O
+and	O
+hyperthermia	O
+.	O
+
+There	O
+was	O
+a	O
+close	O
+correlation	O
+between	O
+plasma	O
+clearance	O
+of	O
+NT	O
+by	O
+10	O
+-	O
+hydroxylation	O
+and	O
+the	O
+D	O
+metabolic	O
+ratio	O
+(	O
+D	O
+/	O
+4	O
+-	O
+OH	O
+-	O
+D	O
+in	O
+urine	O
+)	O
+in	O
+the	O
+Ghanaians	O
+(	O
+rs	O
+=	O
+-	O
+0	O
+.	O
+95	O
+;	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+and	O
+Swedes	O
+(	O
+rs	O
+=	O
+-	O
+0	O
+.	O
+84	O
+;	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+response	O
+properties	O
+of	O
+cat	O
+horizontal	O
+canal	O
+afferents	O
+(	O
+N	O
+=	O
+81	O
+)	O
+were	O
+characterized	O
+by	O
+three	O
+parameters	O
+:	O
+their	O
+long	O
+time	O
+constants	O
+(	O
+tau	O
+)	O
+,	O
+low	O
+frequency	O
+gain	O
+constants	O
+(	O
+G1	O
+)	O
+,	O
+and	O
+middle	O
+frequency	O
+gain	O
+constants	O
+(	O
+Gm	O
+)	O
+.	O
+
+Despite	O
+supraphysiologic	O
+E2	O
+concentrations	O
+,	O
+however	O
+,	O
+cervical	O
+mucus	O
+scores	O
+were	O
+significantly	O
+reduced	O
+in	O
+the	O
+CC	O
+-	O
+treated	O
+group	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Stimulation	O
+of	O
+the	O
+caudate	O
+nucleus	O
+'	O
+dophamine	O
+-	O
+reactive	O
+system	O
+in	O
+dogs	O
+by	O
+means	O
+of	O
+administration	O
+of	O
+dophamine	O
+(	O
+60	O
+micrograms	O
+)	O
+and	O
+phenamine	O
+led	O
+to	O
+deterioration	O
+of	O
+conditioned	O
+and	O
+unconditioned	O
+components	O
+of	O
+feeding	O
+behaviour	O
+.	O
+
+Value	O
+of	O
+urine	O
+glucose	O
+tests	O
+in	O
+the	O
+management	O
+of	O
+type	O
+II	O
+diabetes	O
+mellitus	O
+.	O
+
+This	O
+experiment	O
+was	O
+conducted	O
+to	O
+determine	O
+if	O
+the	O
+sex	O
+or	O
+actual	O
+egg	O
+production	O
+was	O
+the	O
+important	O
+factor	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+A	O
+pharmacokinetic	O
+study	O
+of	O
+apalcillin	O
+was	O
+performed	O
+in	O
+12	O
+patients	O
+in	O
+an	O
+intensive	O
+-	O
+care	O
+unit	O
+.	O
+
+Thrombocyte	O
+function	O
+was	O
+impaired	O
+in	O
+all	O
+patients	O
+,	O
+characterized	O
+by	O
+a	O
+diminished	O
+platelet	O
+shape	O
+change	O
+.	O
+
+The	O
+findings	O
+demonstrate	O
+that	O
+AMPH	O
+administration	O
+induces	O
+a	O
+significant	O
+increase	O
+in	O
+the	O
+height	O
+of	O
+a	O
+major	O
+electroactive	O
+peak	O
+in	O
+the	O
+caudate	O
+nucleus	O
+of	O
+pigtail	O
+monkeys	O
+,	O
+and	O
+further	O
+that	O
+such	O
+amphetamine	O
+-	O
+induced	O
+increases	O
+can	O
+be	O
+manipulated	O
+by	O
+altering	O
+the	O
+affective	O
+and	O
+/	O
+or	O
+emotional	O
+state	O
+of	O
+the	O
+animal	O
+.	O
+
+In	O
+two	O
+experiments	O
+,	O
+neonatal	O
+female	O
+BALB	O
+/	O
+cCrgl	O
+or	O
+BALB	O
+/	O
+cfC3HCrgl	O
+mice	O
+were	O
+given	O
+subcutaneous	O
+injections	O
+of	O
+5	O
+micrograms	O
+17	O
+beta	O
+-	O
+estradiol	O
+or	O
+sesame	O
+oil	O
+for	O
+the	O
+first	O
+3	O
+days	O
+of	O
+life	O
+and	O
+were	O
+ovariectomized	O
+at	O
+60	O
+days	O
+of	O
+age	O
+,	O
+at	O
+which	O
+time	O
+vaginal	O
+concretions	O
+(	O
+Experiments	O
+I	O
+and	O
+II	O
+)	O
+or	O
+silica	O
+(	O
+Experiment	O
+II	O
+)	O
+were	O
+implanted	O
+intravaginally	O
+.	O
+
+For	O
+228	O
+of	O
+425	O
+deaths	O
+(	O
+54	O
+%	O
+)	O
+occurring	O
+among	O
+26	O
+100	O
+people	O
+of	O
+known	O
+age	O
+in	O
+the	O
+Malumfashi	O
+area	O
+of	O
+northern	O
+Nigeria	O
+,	O
+data	O
+were	O
+collected	O
+on	O
+symptoms	O
+present	O
+prior	O
+to	O
+death	O
+.	O
+
+Salivary	O
+estradiol	O
+17	O
+beta	O
+(	O
+E2	O
+-	O
+17	O
+beta	O
+)	O
+and	O
+progesterone	O
+(	O
+P	O
+)	O
+were	O
+determined	O
+by	O
+using	O
+radioimmunoassay	O
+techniques	O
+in	O
+30	O
+pregnant	O
+females	O
+in	O
+the	O
+first	O
+,	O
+second	O
+and	O
+third	O
+trimesters	O
+as	O
+well	O
+as	O
+in	O
+10	O
+non	O
+-	O
+pregnant	O
+controls	O
+during	O
+the	O
+luteal	O
+phase	O
+of	O
+the	O
+menstrual	O
+cycle	O
+.	O
+
+Other	O
+than	O
+d	O
+7	O
+,	O
+there	O
+was	O
+no	O
+significant	O
+effect	O
+on	O
+the	O
+number	O
+of	O
+implants	O
+.	O
+
+Variable	O
+FHR	O
+decelerations	O
+or	O
+bradycardias	O
+were	O
+encountered	O
+on	O
+95	O
+nonstress	O
+tests	O
+(	O
+18	O
+.	O
+8	O
+%	O
+)	O
+in	O
+80	O
+(	O
+33	O
+.	O
+5	O
+%	O
+)	O
+postdate	O
+patients	O
+.	O
+
+The	O
+response	O
+chain	O
+in	O
+each	O
+component	O
+was	O
+maintained	O
+by	O
+food	O
+presentation	O
+under	O
+a	O
+fixed	O
+-	O
+ratio	O
+schedule	O
+.	O
+
+The	O
+results	O
+imply	O
+that	O
+kindling	O
+does	O
+not	O
+produce	O
+its	O
+facilitating	O
+effect	O
+on	O
+acquisition	O
+of	O
+HPC	O
+SS	O
+by	O
+removing	O
+a	O
+disruptive	O
+effect	O
+of	O
+the	O
+stimulation	O
+.	O
+
+The	O
+persistent	O
+fetal	O
+dispersion	O
+of	O
+nodal	O
+and	O
+Hiss	O
+bundle	O
+fragments	O
+within	O
+the	O
+ventricular	O
+septum	O
+is	O
+proposed	O
+as	O
+a	O
+possible	O
+explanation	O
+.	O
+
+According	O
+to	O
+the	O
+biochemical	O
+tests	O
+,	O
+high	O
+activity	O
+(	O
+over	O
+200	O
+U	O
+/	O
+l	O
+)	O
+of	O
+alkaline	B-GENE
+phosphatase	I-GENE
+was	O
+recorded	O
+exclusively	O
+in	O
+patients	O
+with	O
+the	O
+lymphogranulomatosis	O
+-	O
+induced	O
+liver	O
+damage	O
+.	O
+
+Changes	O
+of	O
+plasma	O
+cortisol	O
+level	O
+in	O
+late	O
+asthmatic	O
+responses	O
+
+Significant	O
+alterations	O
+in	O
+the	O
+vasectomized	O
+rats	O
+from	O
+sham	O
+rats	O
+included	O
+:	O
+testicular	O
+and	O
+epididymal	O
+hypertrophy	O
+,	O
+formation	O
+of	O
+pathologic	O
+vas	O
+deferens	O
+granulomas	O
+,	O
+decreased	O
+total	O
+serum	O
+protein	O
+,	O
+lowered	O
+alpha	B-GENE
+-	I-GENE
+globulin	I-GENE
+levels	O
+as	O
+shown	O
+by	O
+serum	O
+electrophoresis	O
+,	O
+and	O
+increased	O
+sperm	O
+agglutinin	B-GENE
+antibody	O
+titers	O
+.	O
+
+SFP	O
+was	O
+significantly	O
+elevated	O
+in	O
+Hn	O
+(	O
+s	O
+)	O
+.	O
+
+The	O
+average	O
+birth	O
+mass	O
+of	O
+these	O
+newborns	O
+was	O
+3491	O
+.	O
+9	O
++	O
+/	O
+-	O
+2	O
+SD	O
+780	O
+.	O
+5	O
+g	O
+and	O
+that	O
+in	O
+the	O
+control	O
+group	O
+3	O
+,	O
+767	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+SD	O
+824	O
+.	O
+2	O
+g	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+This	O
+machine	O
+drift	O
+,	O
+which	O
+was	O
+not	O
+associated	O
+with	O
+a	O
+rise	O
+in	O
+water	O
+phantom	O
+temperature	O
+and	O
+did	O
+not	O
+consistently	O
+correlate	O
+with	O
+estimated	O
+x	O
+-	O
+ray	O
+tube	O
+heat	O
+,	O
+could	O
+result	O
+in	O
+a	O
+significant	O
+overestimation	O
+of	O
+regional	O
+cerebral	O
+blood	O
+flow	O
+(	O
+rCBF	O
+)	O
+for	O
+a	O
+xenon	O
+/	O
+CT	O
+rCBF	O
+protocol	O
+involving	O
+5	O
+-	O
+7	O
+sequential	O
+scans	O
+obtained	O
+at	O
+1	O
+-	O
+min	O
+interscan	O
+intervals	O
+.	O
+
+Other	O
+uncertainties	O
+in	O
+the	O
+dosimetry	O
+at	O
+Y	O
+-	O
+12	O
+and	O
+Vinca	O
+are	O
+unaltered	O
+.	O
+
+E2	O
+treatments	O
+elevated	O
+hen	O
+plasma	O
+TG	O
+7	O
+.	O
+2X	O
+,	O
+PL	O
+5	O
+.	O
+1X	O
+,	O
+and	O
+C	O
+7	O
+.	O
+2X	O
+;	O
+and	O
+pullet	O
+plasma	O
+TG	O
+6	O
+.	O
+8X	O
+,	O
+PL	O
+3	O
+.	O
+7X	O
+,	O
+and	O
+C	O
+2	O
+.	O
+5X	O
+.	O
+
+By	O
+contrast	O
+,	O
+kidneys	O
+from	O
+rats	O
+with	O
+chronic	O
+metabolic	O
+acidosis	O
+produced	O
+significantly	O
+more	O
+NH3	O
+than	O
+both	O
+these	O
+groups	O
+(	O
+2	O
+.	O
+73	O
++	O
+/	O
+-	O
+0	O
+.	O
+29	O
+mumol	O
+X	O
+min	O
+-	O
+1	O
+X	O
+g	O
+-	O
+1	O
+)	O
+.	O
+
+Serodiagnosis	O
+of	O
+trypanosomiasis	O
+in	O
+dromedary	O
+camels	O
+using	O
+a	O
+card	O
+agglutination	O
+test	O
+set	O
+(	O
+Testryp	O
+CATT	O
+)	O
+.	O
+
+Adenyl	B-GENE
+cyclase	I-GENE
+activity	O
+of	O
+gastric	O
+mucosa	O
+in	O
+patients	O
+with	O
+duodenal	O
+ulcer	O
+before	O
+and	O
+after	O
+treatment	O
+
+Proteinuria	O
+-	O
+-	O
+selected	O
+physiopathological	O
+and	O
+clinical	O
+problems	O
+
+However	O
+,	O
+subcutaneously	O
+administered	O
+pneumococci	O
+gave	O
+a	O
+lower	O
+mortality	O
+than	O
+pneumococci	O
+given	O
+intravenously	O
+or	O
+intraperitoneally	O
+.	O
+
+Reaction	O
+of	O
+human	O
+organism	O
+to	O
+exercise	O
+.	O
+
+HA	O
+resulted	O
+in	O
+decreased	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+Tre	O
+(	O
+0	O
+.	O
+4	O
+degrees	O
+C	O
+)	O
+and	O
+HR	O
+(	O
+17	O
+b	O
+X	O
+min	O
+-	O
+1	O
+)	O
+,	O
+and	O
+increased	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+Msw	O
+(	O
+16	O
+g	O
+X	O
+m	O
+-	O
+2	O
+X	O
+h	O
+-	O
+1	O
+)	O
+during	O
+the	O
+saline	O
+experiments	O
+.	O
+
+The	O
+results	O
+obtained	O
+were	O
+as	O
+follows	O
+:	O
+The	O
+mitral	O
+valve	O
+orifice	O
+area	O
+(	O
+MVA	O
+)	O
+was	O
+significantly	O
+smaller	O
+in	O
+patients	O
+with	O
+type	O
+III	O
+of	O
+the	O
+LVIT	O
+flow	O
+velocity	O
+pattern	O
+than	O
+in	O
+patients	O
+with	O
+type	O
+I	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Scientific	O
+cooperation	O
+of	O
+CMEA	O
+member	O
+countries	O
+has	O
+been	O
+carried	O
+out	O
+since	O
+1974	O
+under	O
+the	O
+sponsorship	O
+of	O
+the	O
+Cancer	O
+Research	O
+Institute	O
+,	O
+Slovak	O
+Academy	O
+of	O
+Sciences	O
+(	O
+Czechoslovakia	O
+)	O
+within	O
+the	O
+framework	O
+of	O
+CMEA	O
+.	O
+
+This	O
+compares	O
+favorably	O
+to	O
+results	O
+of	O
+similarly	O
+sized	O
+melanomas	O
+treated	O
+by	O
+enucleation	O
+.	O
+
+A	O
+new	O
+variant	O
+of	O
+the	O
+EMG	O
+-	O
+BFB	O
+method	O
+(	O
+multichannel	O
+)	O
+is	O
+offered	O
+which	O
+has	O
+made	O
+it	O
+possible	O
+to	O
+use	O
+the	O
+method	O
+not	O
+only	O
+for	O
+training	O
+weakened	O
+muscles	O
+and	O
+reducing	O
+spasticity	O
+in	O
+their	O
+antagonists	O
+but	O
+also	O
+for	O
+improving	O
+motor	O
+coordination	O
+.	O
+
+Lymphocytes	O
+from	O
+all	O
+3	O
+species	O
+yielded	O
+maximum	O
+responses	O
+with	O
+a	O
+48	O
+-	O
+hour	O
+prelabel	O
+and	O
+12	O
+-	O
+to	O
+-	O
+16	O
+hour	O
+postlabel	O
+incubation	O
+period	O
+at	O
+41	O
+C	O
+and	O
+1	O
+:	O
+20	O
+blood	O
+dilution	O
+.	O
+
+However	O
+,	O
+there	O
+was	O
+a	O
+difference	O
+in	O
+the	O
+quality	O
+of	O
+immunity	O
+:	O
+fever	O
+and	O
+body	O
+weight	O
+loss	O
+were	O
+seen	O
+in	O
+hamsters	O
+vaccinated	O
+with	O
+the	O
+killed	O
+-	O
+toxoplasma	O
+vaccine	O
+after	O
+they	O
+were	O
+challenge	O
+exposed	O
+with	O
+T	O
+-	O
+1	O
+strain	O
+,	O
+whereas	O
+these	O
+changes	O
+were	O
+rarely	O
+seen	O
+in	O
+hamsters	O
+given	O
+the	O
+live	O
+-	O
+toxoplasma	O
+vaccine	O
+and	O
+then	O
+challenge	O
+exposed	O
+with	O
+RH	O
+strain	O
+.	O
+
+Alternating	O
+proline	O
+/	O
+alanine	O
+sequence	O
+of	O
+beta	B-GENE
+B1	I-GENE
+subunit	I-GENE
+originates	O
+from	O
+a	O
+repetitive	O
+DNA	O
+sequence	O
+.	O
+
+The	O
+segmental	O
+and	O
+regional	O
+projections	O
+of	O
+the	O
+sciatic	O
+,	O
+tibial	O
+and	O
+common	O
+peroneal	O
+nerves	O
+to	O
+the	O
+substantia	O
+gelatinosa	O
+of	O
+the	O
+spinal	O
+cord	O
+in	O
+rats	O
+-	O
+-	O
+an	O
+experimental	O
+study	O
+by	O
+means	O
+of	O
+an	O
+acid	B-GENE
+phosphatase	I-GENE
+(	O
+ACP	B-GENE
+)	O
+method	O
+.	O
+
+Removal	O
+of	O
+lipid	O
+fractions	O
+of	O
+plant	O
+extractions	O
+with	O
+hexane	O
+is	O
+recommended	O
+to	O
+avoid	O
+damage	O
+to	O
+the	O
+HPLC	O
+column	O
+.	O
+
+In	O
+the	O
+Arithmetic	O
+subtest	O
+one	O
+of	O
+the	O
+items	O
+would	O
+not	O
+meet	O
+the	O
+difficulty	O
+grading	O
+shown	O
+while	O
+the	O
+last	O
+two	O
+items	O
+offer	O
+very	O
+little	O
+possibility	O
+of	O
+success	O
+for	O
+all	O
+subjects	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+The	O
+toxicological	O
+evaluation	O
+of	O
+chlorofluorocarbon	O
+22	O
+(	O
+CFC	O
+22	O
+)	O
+.	O
+
+All	O
+patients	O
+were	O
+evaluable	O
+for	O
+toxicity	O
+and	O
+9	O
+for	O
+response	O
+.	O
+
+Methods	O
+of	O
+clinical	O
+and	O
+experimental	O
+algesimetry	O
+are	O
+described	O
+that	O
+have	O
+been	O
+used	O
+to	O
+evaluate	O
+effects	O
+of	O
+peripherally	O
+and	O
+centrally	O
+acting	O
+analgesics	O
+.	O
+
+We	O
+propose	O
+that	O
+the	O
+ambiguous	O
+discrimination	O
+required	O
+a	O
+greater	O
+time	O
+for	O
+simulus	O
+evaluation	O
+and	O
+that	O
+this	O
+was	O
+reflected	O
+in	O
+the	O
+delayed	O
+P3	O
+latencies	O
+.	O
+
+Ammonia	O
+concentration	O
+dropped	O
+significantly	O
+in	O
+all	O
+treatments	O
+,	O
+a	O
+finding	O
+which	O
+suggests	O
+a	O
+protective	O
+effect	O
+on	O
+protein	O
+nitrogen	O
+degradation	O
+to	O
+non	O
+-	O
+protein	O
+nitrogen	O
+(	O
+NH3	O
+)	O
+.	O
+
+In	O
+this	O
+respect	O
+C	B-GENE
+reactive	I-GENE
+protein	I-GENE
+concentrations	O
+are	O
+superior	O
+to	O
+white	O
+cell	O
+count	O
+,	O
+erythrocyte	O
+sedimentation	O
+rate	O
+,	O
+and	O
+temperature	O
+and	O
+the	O
+concentrations	O
+of	O
+antiproteases	O
+.	O
+
+Human	B-GENE
+thyroid	I-GENE
+stimulator	I-GENE
+(	O
+HTS	B-GENE
+)	O
+in	O
+thyroid	O
+diseases	O
+
+We	O
+conclude	O
+that	O
+administration	O
+of	O
+the	O
+calcium	O
+antagonist	O
+Verapamil	O
+is	O
+of	O
+no	O
+additional	O
+value	O
+in	O
+tocolytic	O
+treatment	O
+with	O
+beta	O
+-	O
+mimetics	O
+.	O
+
+Effects	O
+of	O
+ketamine	O
+on	O
+the	O
+circulatory	O
+functions	O
+and	O
+body	O
+tissue	O
+oxygenation	O
+in	O
+dogs	O
+under	O
+normal	O
+and	O
+hypovolemic	O
+conditions	O
+.	O
+
+Besides	O
+,	O
+it	O
+was	O
+considered	O
+that	O
+the	O
+NPF	O
+was	O
+a	O
+useful	O
+tool	O
+for	O
+activation	O
+of	O
+velopharyngeal	O
+activity	O
+by	O
+way	O
+of	O
+visual	O
+feed	O
+-	O
+back	O
+control	O
+.	O
+
+To	O
+evaluate	O
+the	O
+comparative	O
+safety	O
+of	O
+U	O
+-	O
+P	O
+and	O
+D	O
+&	O
+E	O
+,	O
+we	O
+analyzed	O
+2	O
+,	O
+805	O
+U	O
+-	O
+P	O
+and	O
+9	O
+,	O
+572	O
+D	O
+&	O
+E	O
+abortions	O
+at	O
+13	O
+to	O
+24	O
+menstrual	O
+weeks	O
+'	O
+gestation	O
+.	O
+
+Three	O
+radiologists	O
+without	O
+knowledge	O
+of	O
+patients	O
+'	O
+data	O
+and	O
+treatment	O
+analyzed	O
+30	O
+angiograms	O
+with	O
+and	O
+30	O
+examinations	O
+without	O
+PGF	O
+.	O
+
+In	O
+a	O
+man	O
+with	O
+myelomonocytic	O
+leukemia	O
+,	O
+the	O
+association	O
+of	O
+increased	O
+prostatic	B-GENE
+acid	I-GENE
+phosphatase	I-GENE
+activity	O
+in	O
+serum	O
+and	O
+the	O
+presence	O
+of	O
+typical	O
+bone	O
+lesions	O
+on	O
+roentgenography	O
+suggested	O
+the	O
+existence	O
+of	O
+disseminated	O
+prostatic	O
+carcinoma	O
+.	O
+
+An	O
+experimental	O
+long	O
+-	O
+term	O
+study	O
+.	O
+
+No	O
+anisotropism	O
+was	O
+recorded	O
+in	O
+a	O
+tetrahydrofuran	O
+solution	O
+.	O
+
+The	O
+calculated	O
+values	O
+of	O
+lambda	O
+tb	O
+at	O
+37	O
+degrees	O
+C	O
+and	O
+50	O
+per	O
+cent	O
+haematocrit	O
+were	O
+0	O
+.	O
+650	O
+for	O
+the	O
+pulp	O
+,	O
+0	O
+.	O
+674	O
+for	O
+the	O
+tongue	O
+,	O
+0	O
+.	O
+828	O
+for	O
+the	O
+submandibular	O
+gland	O
+and	O
+0	O
+.	O
+881	O
+for	O
+the	O
+gingiva	O
+of	O
+the	O
+dog	O
+.	O
+lambda	O
+cp	O
+increased	O
+and	O
+lambda	O
+tp	O
+decreased	O
+as	O
+the	O
+temperature	O
+was	O
+reduced	O
+from	O
+37	O
+to	O
+4	O
+degrees	O
+C	O
+.	O
+
+As	O
+pleural	O
+thickening	O
+is	O
+seen	O
+commonly	O
+in	O
+asbestosis	O
+and	O
+may	O
+influence	O
+lung	O
+volumes	O
+and	O
+the	O
+ratio	O
+of	O
+transfer	B-GENE
+factor	I-GENE
+to	O
+effective	O
+alveolar	O
+volume	O
+,	O
+the	O
+results	O
+of	O
+these	O
+measurements	O
+were	O
+compared	O
+only	O
+in	O
+the	O
+cases	O
+showing	O
+absent	O
+or	O
+minimal	O
+pleural	O
+thickening	O
+.	O
+
+The	O
+invasive	O
+pattern	O
+of	O
+squamous	O
+cell	O
+carcinoma	O
+in	O
+the	O
+mandibular	O
+gingiva	O
+
+Azygos	O
+vein	O
+abutting	O
+the	O
+posterior	O
+wall	O
+of	O
+the	O
+right	O
+main	O
+and	O
+upper	O
+lobe	O
+bronchi	O
+:	O
+a	O
+normal	O
+CT	O
+variant	O
+.	O
+
+However	O
+,	O
+the	O
+history	O
+of	O
+acute	O
+severe	O
+complications	O
+from	O
+otitis	O
+media	O
+revealed	O
+a	O
+higher	O
+frequency	O
+in	O
+those	O
+individuals	O
+with	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+antitrypsin	I-GENE
+deficiency	O
+as	O
+compared	O
+to	O
+normals	O
+.	O
+
+All	O
+other	O
+changes	O
+at	O
+the	O
+3	O
+-	O
+,	O
+5	O
+-	O
+,	O
+and	O
+6	O
+-	O
+positions	O
+,	O
+as	O
+well	O
+as	O
+the	O
+replacement	O
+of	O
+the	O
+phenyl	O
+group	O
+at	O
+position	O
+2	O
+,	O
+caused	O
+a	O
+marked	O
+decrease	O
+of	O
+activity	O
+.	O
+
+Limb	O
+allografts	O
+in	O
+rats	O
+immunosuppressed	O
+with	O
+cyclosporin	O
+A	O
+.	O
+
+The	O
+method	O
+involved	O
+deproteinizing	O
+samples	O
+with	O
+two	O
+volumes	O
+of	O
+acetonitrile	O
+followed	O
+by	O
+injection	O
+of	O
+5	O
+microliters	O
+of	O
+deproteinized	O
+supernatant	O
+onto	O
+a	O
+C18	O
+reversed	O
+-	O
+phase	O
+column	O
+.	O
+
+Refractory	O
+periods	O
+of	O
+the	O
+AV	O
+junction	O
+were	O
+altered	O
+in	O
+a	O
+comparable	O
+fashion	O
+to	O
+conduction	O
+through	O
+the	O
+AV	O
+node	O
+.	O
+
+This	O
+paper	O
+brings	O
+together	O
+data	O
+,	O
+obtained	O
+from	O
+a	O
+variety	O
+of	O
+sources	O
+,	O
+on	O
+the	O
+extent	O
+of	O
+prescription	O
+and	O
+use	O
+of	O
+psychotropic	O
+drugs	O
+in	O
+the	O
+late	O
+1960s	O
+and	O
+early	O
+1970s	O
+.	O
+
+Sixteen	O
+patients	O
+were	O
+studied	O
+within	O
+24	O
+hours	O
+of	O
+resuscitation	O
+and	O
+all	O
+showed	O
+depressed	O
+right	O
+ventricular	O
+ejection	O
+(	O
+RVEF	O
+)	O
+and	O
+/	O
+or	O
+an	O
+increased	O
+end	O
+-	O
+diastolic	O
+volume	O
+(	O
+RVEDVI	O
+)	O
+.	O
+
+During	O
+a	O
+single	O
+LAD	O
+occlusion	O
+lasting	O
+35	O
+minutes	O
+(	O
+series	O
+I	O
+,	O
+n	O
+=	O
+10	O
+)	O
+9	O
+microns	O
+TMs	O
+were	O
+infused	O
+immediately	O
+and	O
+30	O
+minutes	O
+after	O
+ligation	O
+,	O
+15	O
+microns	O
+TMs	O
+being	O
+infused	O
+after	O
+15	O
+-	O
+20	O
+minutes	O
+.	O
+
+The	O
+population	O
+of	O
+between	O
+75	O
+,	O
+000	O
+and	O
+100	O
+,	O
+000	O
+was	O
+largely	O
+unstable	O
+,	O
+and	O
+cost	O
+per	O
+capita	O
+was	O
+$	O
+0	O
+.	O
+95	O
+to	O
+$	O
+1	O
+.	O
+21	O
+.	O
+
+HL	O
+02	O
+type	O
+oculomotor	O
+stimulator	O
+.	O
+
+Four	O
+patients	O
+(	O
+group	O
+1	O
+)	O
+had	O
+type	O
+I	O
+basement	O
+membrane	O
+nephropathy	O
+,	O
+characterized	O
+by	O
+marked	O
+thickening	O
+and	O
+lamellation	O
+of	O
+the	O
+basement	O
+membrane	O
+in	O
+a	O
+pattern	O
+resembling	O
+that	O
+of	O
+Alport	O
+'	O
+s	O
+syndrome	O
+.	O
+
+Brain	O
+pH	O
+following	O
+3	O
+h	O
+of	O
+cerebral	O
+focal	O
+ischemia	O
+changed	O
+from	O
+a	O
+normal	O
+value	O
+of	O
+7	O
+.	O
+0	O
+to	O
+6	O
+.	O
+5	O
+and	O
+6	O
+.	O
+2	O
+in	O
+animals	O
+studied	O
+under	O
+barbiturate	O
+and	O
+halothane	O
+anesthesia	O
+,	O
+respectively	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+the	O
+importance	O
+of	O
+phosphate	O
+and	O
+calcium	O
+in	O
+influencing	O
+the	O
+secretion	O
+of	O
+PTH	B-GENE
+and	O
+CT	B-GENE
+in	O
+uremia	O
+.	O
+
+Thin	O
+-	O
+layer	O
+chromatographic	O
+methods	O
+were	O
+up	O
+-	O
+dated	O
+for	O
+pharmacokinetic	O
+studies	O
+of	O
+imipramine	O
+in	O
+plasma	O
+and	O
+urine	O
+.	O
+
+Increasing	O
+the	O
+cut	O
+-	O
+off	O
+point	O
+to	O
+3	O
+positive	O
+responses	O
+decreased	O
+the	O
+sensitivity	O
+to	O
+81	O
+%	O
+and	O
+increased	O
+the	O
+specificity	O
+to	O
+94	O
+%	O
+.	O
+
+After	O
+clofelin	O
+administration	O
+the	O
+autoregulation	O
+borders	O
+shifted	O
+to	O
+the	O
+right	O
+i	O
+.	O
+e	O
+.	O
+towards	O
+higher	O
+AP	O
+levels	O
+.	O
+
+This	O
+phenomenon	O
+may	O
+be	O
+regarded	O
+as	O
+a	O
+variant	O
+of	O
+selective	O
+individual	O
+cell	O
+death	O
+,	O
+currently	O
+referred	O
+to	O
+as	O
+apoptosis	O
+,	O
+which	O
+has	O
+not	O
+been	O
+previously	O
+reported	O
+in	O
+a	O
+case	O
+of	O
+embryonal	O
+rhabdomyosarcoma	O
+.	O
+
+A	O
+combined	O
+series	O
+of	O
+patients	O
+experienced	O
+a	O
+TOL	O
+after	O
+two	O
+or	O
+more	O
+previous	O
+cesarean	O
+deliveries	O
+;	O
+the	O
+rate	O
+of	O
+vaginal	O
+delivery	O
+was	O
+66	O
+%	O
+,	O
+and	O
+there	O
+was	O
+virtually	O
+no	O
+morbidity	O
+.	O
+
+Nursing	O
+home	O
+discharges	O
+in	O
+clinical	O
+practice	O
+.	O
+
+The	O
+carcinogen	O
+bioassay	O
+therefore	O
+is	O
+a	O
+very	O
+important	O
+component	O
+of	O
+the	O
+battery	O
+of	O
+toxicological	O
+tests	O
+used	O
+in	O
+hazard	O
+evaluation	O
+.	O
+
+Harmful	O
+effects	O
+in	O
+animals	O
+and	O
+man	O
+may	O
+result	O
+from	O
+both	O
+deficient	O
+or	O
+excessive	O
+amounts	O
+of	O
+intake	O
+.	O
+
+Angionephroscintigraphy	O
+in	O
+the	O
+diagnosis	O
+of	O
+diseases	O
+of	O
+the	O
+kidney	O
+
+The	O
+analysis	O
+of	O
+the	O
+structure	O
+of	O
+the	O
+sleep	O
+period	O
+as	O
+a	O
+whole	O
+reveals	O
+that	O
+with	O
+increasing	O
+of	O
+the	O
+age	O
+the	O
+delta	O
+-	O
+wave	O
+stage	O
+(	O
+DS	O
+)	O
+of	O
+the	O
+QS	O
+(	O
+determined	O
+by	O
+defined	O
+polygraphic	O
+parameters	O
+)	O
+increases	O
+,	O
+while	O
+the	O
+paradoxical	O
+phase	O
+of	O
+sleep	O
+(	O
+PS	O
+)	O
+decreases	O
+,	O
+this	O
+change	O
+being	O
+more	O
+pronounced	O
+during	O
+the	O
+first	O
+six	O
+months	O
+than	O
+during	O
+the	O
+second	O
+ones	O
+of	O
+the	O
+first	O
+year	O
+of	O
+the	O
+life	O
+.	O
+
+[	O
+82Br	O
+]	O
+MISO	O
+was	O
+prepared	O
+by	O
+irradiating	O
+samples	O
+of	O
+Br	O
+-	O
+MISO	O
+in	O
+a	O
+SLOWPOKE	O
+reactor	O
+for	O
+2	O
+h	O
+at	O
+a	O
+thermal	O
+neutron	O
+flux	O
+of	O
+10	O
+(	O
+12	O
+)	O
+n	O
+cm	O
+-	O
+2	O
+s	O
+-	O
+1	O
+.	O
+
+Morphofunctional	O
+status	O
+of	O
+the	O
+formed	O
+elements	O
+of	O
+the	O
+blood	O
+in	O
+rats	O
+subjected	O
+to	O
+different	O
+variants	O
+of	O
+combined	O
+and	O
+isolated	O
+exposure	O
+to	O
+BR	O
+-	O
+1	O
+benzene	O
+
+The	O
+liver	O
+in	O
+the	O
+severely	O
+ill	O
+
+In	O
+a	O
+randomized	O
+study	O
+on	O
+150	O
+patients	O
+(	O
+ASA	O
+1	O
+)	O
+undergoing	O
+induction	O
+of	O
+anaesthesia	O
+,	O
+the	O
+effects	O
+of	O
+Fentanyl	O
+(	O
+0	O
+.	O
+1	O
+mg	O
+)	O
+,	O
+the	O
+combination	O
+of	O
+Fentanyl	O
+(	O
+0	O
+.	O
+1	O
+mg	O
+)	O
+and	O
+Droperidol	O
+(	O
+5	O
+mg	O
+)	O
+(	O
+Innovar	O
+,	O
+Thalamonal	O
+)	O
+and	O
+Atropine	O
+(	O
+0	O
+.	O
+01	O
+mg	O
+/	O
+kg	O
+b	O
+.	O
+w	O
+.	O
+)	O
+alone	O
+on	O
+cardiocirculatory	O
+parameters	O
+were	O
+studied	O
+.	O
+
+These	O
+results	O
+confirming	O
+the	O
+high	O
+validity	O
+of	O
+NOM	O
+inhibiting	O
+test	O
+in	O
+the	O
+diagnosis	O
+of	O
+tumoural	O
+hyperprolactinemic	O
+states	O
+,	O
+reveal	O
+contradictory	O
+responses	O
+to	O
+CD	O
+/	O
+LD	O
+,	O
+LD	O
+and	O
+DOM	O
+,	O
+with	O
+sustain	O
+the	O
+existence	O
+of	O
+2	O
+sub	O
+-	O
+group	O
+of	O
+Prolactinomas	O
+:	O
+with	O
+or	O
+without	O
+a	O
+maintained	O
+DA	O
+central	O
+tonus	O
+supporting	O
+the	O
+possibility	O
+of	O
+different	O
+etiopathogenetical	O
+factors	O
+in	O
+inducing	O
+a	O
+tumoural	O
+hyperprolactinemic	O
+states	O
+.	O
+
+Low	O
+NA	O
+and	O
+A	O
+may	O
+participate	O
+in	O
+lowering	O
+the	O
+plasma	B-GENE
+renin	I-GENE
+activity	O
+which	O
+in	O
+PA	O
+in	O
+suppressed	O
+,	O
+sometimes	O
+disproportionately	O
+to	O
+the	O
+actual	O
+body	O
+sodium	O
+content	O
+.	O
+
+Amikacin	O
+concentrations	O
+in	O
+serum	O
+and	O
+blister	O
+fluid	O
+in	O
+healthy	O
+volunteers	O
+and	O
+in	O
+patients	O
+with	O
+renal	O
+impairment	O
+.	O
+
+The	O
+subgroup	O
+innervating	O
+the	O
+medial	O
+rectus	O
+lies	O
+exclusively	O
+along	O
+the	O
+medial	O
+face	O
+of	O
+the	O
+oculomotor	O
+nucleus	O
+,	O
+with	O
+no	O
+aberrant	O
+neurons	O
+in	O
+the	O
+medial	O
+longitudinal	O
+fasciculus	O
+,	O
+as	O
+have	O
+been	O
+found	O
+in	O
+other	O
+mammals	O
+.	O
+
+Hepatitis	O
+B	O
+vaccination	O
+strategy	O
+for	O
+health	O
+-	O
+care	O
+workers	O
+in	O
+a	O
+country	O
+of	O
+intermediate	O
+hepatitis	O
+B	O
+endemicity	O
+.	O
+
+An	O
+intravenous	O
+drip	O
+infusion	O
+of	O
+AMK	O
+in	O
+adequate	O
+dosage	O
+would	O
+be	O
+beneficial	O
+to	O
+use	O
+against	O
+some	O
+infectious	O
+diseases	O
+of	O
+otorhinolaryngologic	O
+field	O
+.	O
+
+Out	O
+of	O
+these	O
+families	O
+74	O
+,	O
+3	O
+%	O
+planned	O
+next	O
+pregnancy	O
+(	O
+table	O
+IX	O
+)	O
+,	O
+57	O
+,	O
+6	O
+%	O
+wanted	O
+to	O
+have	O
+prenatal	O
+diagnosis	O
+(	O
+table	O
+VI	O
+)	O
+.	O
+
+The	O
+authors	O
+have	O
+tested	O
+the	O
+interference	O
+of	O
+the	O
+hemoglobin	B-GENE
+by	O
+two	O
+routine	O
+methods	O
+(	O
+Berthelot	O
+classic	O
+and	O
+Berthelot	O
+modified	O
+)	O
+for	O
+the	O
+determination	O
+of	O
+plasmatic	O
+urea	O
+.	O
+
+Parkinsonian	O
+patients	O
+had	O
+a	O
+significantly	O
+lower	O
+prevalence	O
+of	O
+alcohol	O
+use	O
+.	O
+
+These	O
+cells	O
+averaged	O
+17	O
+microns	O
+in	O
+diameter	O
+and	O
+reproduced	O
+by	O
+fission	O
+,	O
+forming	O
+clusters	O
+of	O
+two	O
+or	O
+four	O
+daughter	O
+cells	O
+.	O
+
+Female	O
+but	O
+not	O
+male	O
+mortalities	O
+were	O
+significantly	O
+higher	O
+for	O
+cake	O
+-	O
+fed	O
+rats	O
+than	O
+for	O
+those	O
+fed	O
+diet	O
+41B	O
+.	O
+
+Urinary	B-GENE
+N	I-GENE
+-	I-GENE
+acetylglucosaminidase	I-GENE
+activity	O
+per	O
+mg	O
+creatinine	O
+did	O
+not	O
+differ	O
+significantly	O
+between	O
+groups	O
+.	O
+
+The	O
+associations	O
+between	O
+sex	B-GENE
+-	I-GENE
+hormone	I-GENE
+-	I-GENE
+binding	I-GENE
+globulin	I-GENE
+capacity	O
+(	O
+SHBG	B-GENE
+)	O
+,	O
+age	O
+,	O
+body	O
+mass	O
+index	O
+(	O
+BMI	O
+)	O
+,	O
+and	O
+physical	O
+fitness	O
+have	O
+been	O
+studied	O
+in	O
+34	O
+men	O
+and	O
+36	O
+women	O
+.	O
+
+Dipetalonema	O
+(	O
+Alafilaria	O
+)	O
+hydrochoerus	O
+subgen	O
+.	O
+et	O
+sp	O
+.	O
+n	O
+.	O
+
+After	O
+1	O
+.	O
+5	O
+years	O
+of	O
+such	O
+photoperiodic	O
+control	O
+,	O
+all	O
+ewes	O
+were	O
+blinded	O
+by	O
+bilateral	O
+orbital	O
+enucleation	O
+.	O
+
+The	O
+concentrations	O
+of	O
+C4	B-GENE
+and	O
+C1	B-GENE
+-	I-GENE
+INH	I-GENE
+increased	O
+with	O
+advancing	O
+stage	O
+of	O
+disease	O
+and	O
+were	O
+above	O
+normal	O
+mean	O
+values	O
+in	O
+all	O
+stages	O
+.	O
+
+Less	O
+antibacterial	O
+activity	O
+was	O
+shown	O
+toward	O
+the	O
+Gram	O
+-	O
+negative	O
+bacilli	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+Pseudomonas	O
+,	O
+Klebsiella	O
+-	O
+Enterobacter	O
+,	O
+Shigella	O
+,	O
+Escherichia	O
+coli	O
+,	O
+Serratia	O
+marcescens	O
+and	O
+Proteus	O
+.	O
+
+The	O
+mucosal	O
+defence	O
+capacity	O
+against	O
+proteolytic	O
+leukocyte	O
+enzymes	O
+.	O
+
+The	O
+apparatus	O
+consists	O
+of	O
+an	O
+Am	O
+-	O
+241	O
+exciting	O
+source	O
+(	O
+300	O
+mCi	O
+)	O
+and	O
+pure	O
+Ge	O
+detector	O
+(	O
+50	O
+mm2	O
+X	O
+5	O
+mm	O
+)	O
+for	O
+measuring	O
+K	O
+alpha	O
+fluorescent	O
+x	O
+-	O
+rays	O
+(	O
+28	O
+.	O
+3	O
+and	O
+28	O
+.	O
+6	O
+KeV	O
+)	O
+emitted	O
+from	O
+exited	O
+iodine	O
+.	O
+
+Ultrastructural	O
+studies	O
+of	O
+retinopathy	O
+of	O
+premature	O
+infants	O
+
+The	O
+range	O
+of	O
+serum	O
+concentrations	O
+,	O
+mean	O
+values	O
+,	O
+median	O
+values	O
+,	O
+and	O
+standard	O
+deviations	O
+for	O
+each	O
+analyte	O
+are	O
+reported	O
+for	O
+males	O
+and	O
+females	O
+and	O
+for	O
+three	O
+age	O
+groups	O
+(	O
+25	O
+-	O
+44	O
+,	O
+45	O
+-	O
+59	O
+,	O
+60	O
+-	O
+70	O
+)	O
+.	O
+
+The	O
+effects	O
+of	O
+antithrombotic	O
+drugs	O
+in	O
+patients	O
+with	O
+left	O
+ventricular	O
+thrombi	O
+:	O
+assessment	O
+with	O
+indium	O
+-	O
+111	O
+platelet	O
+imaging	O
+and	O
+two	O
+-	O
+dimensional	O
+echocardiography	O
+.	O
+
+A	O
+stable	O
+interface	O
+depends	O
+on	O
+overall	O
+stress	O
+and	O
+microstress	O
+distribution	O
+on	O
+the	O
+bone	O
+,	O
+particularly	O
+trabecular	O
+bone	O
+.	O
+
+Plasma	O
+NE	O
+was	O
+also	O
+low	O
+in	O
+the	O
+anephric	O
+group	O
+(	O
+289	O
+mg	O
+/	O
+liter	O
++	O
+/	O
+-	O
+126	O
+(	O
+1	O
+SD	O
+)	O
+vs	O
+612	O
++	O
+/	O
+-	O
+189	O
+,	O
+P	O
+=	O
+0	O
+.	O
+033	O
+,	O
+resting	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+10	O
+long	O
+-	O
+term	O
+hemodialysis	O
+patients	O
+had	O
+immediate	O
+and	O
+redistribution	O
+thallium	O
+-	O
+201	O
+myocardial	O
+imaging	O
+performed	O
+after	O
+a	O
+course	O
+of	O
+hemodialysis	O
+.	O
+
+The	O
+Prolactin	B-GENE
+levels	O
+were	O
+within	O
+the	O
+physiological	O
+norms	O
+;	O
+the	O
+responses	O
+to	O
+TRH	B-GENE
+were	O
+normal	O
+,	O
+and	O
+elevated	O
+only	O
+in	O
+a	O
+few	O
+cases	O
+.	O
+
+Despite	O
+total	O
+tumor	O
+resection	O
+,	O
+multiple	O
+intraperitoneal	O
+tumor	O
+nodules	O
+of	O
+varying	O
+sizes	O
+were	O
+found	O
+and	O
+resected	O
+six	O
+months	O
+and	O
+one	O
+year	O
+later	O
+.	O
+
+Private	O
+hospital	O
+accreditation	O
+.	O
+
+Antithrombin	B-GENE
+III	I-GENE
+in	O
+hip	O
+surgery	O
+
+In	O
+14	O
+of	O
+21	O
+infant	O
+hearts	O
+(	O
+66	O
+%	O
+)	O
+with	O
+aortic	O
+arch	O
+interruption	O
+between	O
+the	O
+left	O
+common	O
+carotid	O
+and	O
+left	O
+subclavian	O
+arteries	O
+(	O
+type	O
+B	O
+of	O
+Celoria	O
+and	O
+Patton	O
+)	O
+,	O
+the	O
+right	O
+subclavian	O
+artery	O
+(	O
+SA	O
+)	O
+arose	O
+anomalously	O
+.	O
+
+We	O
+suggest	O
+that	O
+sensitivity	O
+to	O
+photoperiod	O
+in	O
+pallid	O
+bats	O
+,	O
+as	O
+in	O
+several	O
+other	O
+mammals	O
+,	O
+is	O
+mediated	O
+by	O
+the	O
+pineal	O
+gland	O
+.	O
+
+Absorption	O
+was	O
+rapid	O
+,	O
+with	O
+a	O
+mean	O
+time	O
+to	O
+peak	O
+of	O
+39	O
+min	O
+.	O
+
+Additionally	O
+,	O
+observations	O
+that	O
+patients	O
+with	O
+mitral	O
+versus	O
+aortic	O
+regurgitation	O
+respond	O
+differently	O
+to	O
+valve	O
+replacement	O
+suggest	O
+that	O
+differences	O
+exist	O
+preoperatively	O
+between	O
+these	O
+two	O
+types	O
+of	O
+volume	O
+overload	O
+.	O
+
+A	O
+case	O
+of	O
+manifest	O
+latent	O
+nystagmus	O
+of	O
+late	O
+onset	O
+in	O
+a	O
+13	O
+-	O
+year	O
+-	O
+old	O
+girl	O
+is	O
+reported	O
+.	O
+
+Within	O
+the	O
+compartment	O
+or	O
+dimension	O
+of	O
+severity	O
+of	O
+depression	O
+a	O
+subscale	O
+of	O
+the	O
+Hamilton	O
+Depression	O
+Scale	O
+(	O
+or	O
+the	O
+Melancholia	O
+Scale	O
+)	O
+was	O
+shown	O
+to	O
+have	O
+reached	O
+an	O
+instrumental	O
+perfection	O
+,	O
+e	O
+.	O
+g	O
+.	O
+as	O
+an	O
+outcome	O
+measure	O
+of	O
+antidepressant	O
+treatment	O
+.	O
+
+Significant	O
+immunoglobulinuria	O
+developed	O
+prior	O
+to	O
+the	O
+development	O
+of	O
+azotemia	O
+,	O
+significantly	O
+decreased	O
+creatinine	O
+clearance	O
+,	O
+significant	O
+proteinuria	O
+(	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+3	O
++	O
+dipstick	O
+or	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+5	O
+gm	O
+per	O
+24	O
+-	O
+hour	O
+urine	O
+collection	O
+)	O
+,	O
+or	O
+oliguria	O
+.	O
+
+A	O
+total	O
+number	O
+of	O
+1628	O
+cases	O
+were	O
+collected	O
+from	O
+135	O
+medical	O
+institutions	O
+.	O
+
+Epileptiform	O
+activity	O
+recorded	O
+from	O
+superficial	O
+laminae	O
+bordering	O
+layer	O
+4	O
+,	O
+and	O
+into	O
+which	O
+layer	O
+4	O
+'	O
+s	O
+primary	O
+projections	O
+terminate	O
+,	O
+is	O
+suppressed	O
+preferentially	O
+by	O
+phenytoin	O
+.	O
+
+Is	O
+nisoldipine	O
+capable	O
+of	O
+reducing	O
+left	O
+ventricular	O
+preload	O
+?	O
+In	O
+ten	O
+anesthetized	O
+pigs	O
+,	O
+nisoldipine	O
+(	O
+2	O
+-	O
+4	O
+micrograms	O
+X	O
+kg	O
+-	O
+1	O
+X	O
+min	O
+-	O
+1	O
+)	O
+,	O
+a	O
+calcium	O
+channel	O
+blocker	O
+structurally	O
+related	O
+to	O
+nifedipine	O
+,	O
+reduced	O
+left	O
+ventricular	O
+systolic	O
+pressure	O
+(	O
+40	O
+%	O
+)	O
+and	O
+systemic	O
+vascular	O
+resistance	O
+(	O
+35	O
+%	O
+)	O
+,	O
+whereas	O
+maxLVdP	O
+/	O
+dt	O
+decreased	O
+by	O
+20	O
+%	O
+and	O
+cardiac	O
+output	O
+was	O
+unchanged	O
+.	O
+
+Monkeys	O
+were	O
+evaluated	O
+before	O
+and	O
+after	O
+unilateral	O
+and	O
+serial	O
+bilateral	O
+removal	O
+of	O
+superior	O
+temporal	O
+cortex	O
+.	O
+
+Plasma	B-GENE
+lactoferrin	I-GENE
+and	O
+the	O
+blood	O
+count	O
+of	O
+polynuclear	O
+neutrophils	O
+
+The	O
+importance	O
+of	O
+selective	O
+renal	O
+vein	O
+phlebography	O
+in	O
+the	O
+evaluation	O
+of	O
+unexplained	O
+hematuria	O
+and	O
+filing	O
+defects	O
+in	O
+the	O
+excretory	O
+urogram	O
+is	O
+illustrated	O
+.	O
+
+The	O
+statistical	O
+analysis	O
+consist	O
+of	O
+the	O
+F	O
+test	O
+followed	O
+by	O
+Snedecor	O
+'	O
+s	O
+contrast	O
+test	O
+.	O
+
+The	O
+pyramidal	O
+tract	O
+and	O
+Mesencephalic	O
+Reticular	O
+Formation	O
+(	O
+MRF	O
+)	O
+were	O
+stimulated	O
+before	O
+and	O
+after	O
+the	O
+transection	O
+.	O
+
+No	O
+patient	O
+with	O
+bradyarrhythmia	O
+-	O
+related	O
+SCD	O
+had	O
+manifest	O
+atrioventricular	O
+block	O
+or	O
+bundle	O
+branch	O
+block	O
+.	O
+
+The	O
+measurement	O
+of	O
+the	O
+areas	O
+of	O
+fibrin	B-GENE
+,	O
+of	O
+tissue	O
+and	O
+fibrinolysis	O
+,	O
+at	O
+the	O
+above	O
+mentioned	O
+times	O
+,	O
+has	O
+been	O
+effected	O
+at	O
+standard	O
+magnification	O
+(	O
+15	O
+X	O
+)	O
+by	O
+an	O
+image	O
+analyser	O
+(	O
+Videoplan	O
+)	O
+scale	O
+1	O
+:	O
+8	O
+.	O
+
+Diclofenac	O
+sodium	O
+-	O
+chlormezanone	O
+poisoning	O
+.	O
+
+Postprandial	O
+plasma	B-GENE
+enteroglucagon	I-GENE
+concentration	O
+after	O
+90	O
+minutes	O
+in	O
+untreated	O
+patients	O
+correlated	O
+positively	O
+to	O
+the	O
+faecal	O
+fat	O
+excretion	O
+(	O
+r	O
+=	O
+0	O
+.	O
+58	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+Blood	O
+pressure	O
+in	O
+children	O
+.	O
+
+In	O
+this	O
+study	O
+the	O
+splenectomized	O
+captive	O
+born	O
+cynomolgus	O
+appeared	O
+to	O
+be	O
+capable	O
+of	O
+supplementing	O
+rhesus	O
+as	O
+an	O
+antimalarial	O
+drug	O
+testing	O
+model	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+the	O
+sensitivity	O
+of	O
+the	O
+3	O
+given	O
+guinea	O
+pig	O
+strains	O
+was	O
+comparable	O
+.	O
+
+Adult	O
+Amblyomma	O
+lepidum	O
+ticks	O
+fed	O
+as	O
+nymphs	O
+on	O
+this	O
+goat	O
+transmitted	O
+heartwater	O
+to	O
+a	O
+Friesian	O
+(	O
+Bos	O
+taurus	O
+)	O
+calf	O
+.	O
+
+Morphine	O
+injected	O
+into	O
+the	O
+lateral	O
+ventricle	O
+of	O
+the	O
+rat	O
+produced	O
+unilateral	O
+analgesia	O
+in	O
+the	O
+formalin	O
+test	O
+,	O
+which	O
+involves	O
+continuous	O
+,	O
+moderate	O
+pain	O
+.	O
+
+The	O
+maps	O
+of	O
+Case	O
+2	O
+showed	O
+that	O
+a	O
+maximum	O
+first	O
+appeared	O
+on	O
+the	O
+upper	O
+right	O
+back	O
+and	O
+then	O
+moved	O
+down	O
+the	O
+right	O
+side	O
+of	O
+the	O
+posterior	O
+thorax	O
+.	O
+
+Urinary	O
+urate	O
+excretion	O
+,	O
+urate	O
+clearance	O
+,	O
+and	O
+fractional	O
+excretion	O
+of	O
+urate	O
+all	O
+increased	O
+significantly	O
+during	O
+water	O
+immersion	O
+,	O
+and	O
+decreased	O
+in	O
+the	O
+hour	O
+following	O
+water	O
+immersion	O
+.	O
+
+Mutations	O
+in	O
+seven	O
+other	O
+lts	B-GENE
+genes	I-GENE
+do	O
+not	O
+result	O
+in	O
+the	O
+mak	B-GENE
+-	I-GENE
+phenotype	I-GENE
+.	O
+
+Twenty	O
+-	O
+eight	O
+were	O
+excluded	O
+as	O
+gallstones	O
+were	O
+not	O
+proved	O
+:	O
+of	O
+the	O
+remainder	O
+,	O
+21	O
+patients	O
+received	O
+glucagon	B-GENE
+and	O
+22	O
+placebo	O
+.	O
+
+4	O
+Five	O
+patients	O
+died	O
+within	O
+one	O
+month	O
+of	O
+captopril	O
+and	O
+five	O
+between	O
+four	O
+and	O
+seven	O
+months	O
+,	O
+three	O
+of	O
+whom	O
+had	O
+improved	O
+to	O
+class	O
+IIM	O
+and	O
+one	O
+to	O
+IIS	O
+before	O
+death	O
+.	O
+
+Regions	O
+of	O
+the	O
+translated	O
+open	O
+reading	O
+frames	O
+of	O
+cobA	B-GENE
+and	O
+the	O
+third	O
+intron	O
+of	O
+the	O
+cob	B-GENE
+gene	I-GENE
+in	I-GENE
+yeast	I-GENE
+show	O
+high	O
+amino	O
+acid	O
+homology	O
+.	O
+
+Multiresistant	O
+strains	O
+isolated	O
+from	O
+humans	O
+in	O
+enteral	O
+toxico	O
+-	O
+infections	O
+kill	O
+orally	O
+infected	O
+mice	O
+more	O
+frequently	O
+than	O
+strains	O
+isolated	O
+in	O
+hospital	O
+infections	O
+.	O
+
+Single	O
+tooth	O
+replacement	O
+with	O
+the	O
+aid	O
+of	O
+the	O
+ITI	O
+(	O
+International	O
+Team	O
+fur	O
+Implantologie	O
+)	O
+type	O
+F	O
+hollow	O
+-	O
+cylinder	O
+implant	O
+
+The	O
+13	O
+,	O
+14	O
+-	O
+dihydro	O
+-	O
+15	O
+-	O
+keto	O
+-	O
+metabolites	O
+of	O
+PGE2	O
+and	O
+PGF2	O
+alpha	O
+had	O
+no	O
+statistically	O
+significant	O
+antiarrhythmic	O
+effect	O
+.	O
+
+Nucleotide	O
+sequence	O
+of	O
+DNA	O
+controlling	O
+expression	O
+of	O
+genes	O
+for	O
+maltosaccharide	O
+utilization	O
+in	O
+Streptococcus	O
+pneumoniae	O
+.	O
+
+Colorimetric	O
+determination	O
+of	O
+urinary	O
+iron	O
+,	O
+chelated	O
+with	O
+deferoxamine	O
+B	O
+,	O
+using	O
+a	O
+single	O
+reagent	O
+
+Measurements	O
+of	O
+perfusion	O
+also	O
+showed	O
+significantly	O
+higher	O
+values	O
+under	O
+active	O
+therapy	O
+.	O
+
+HLA	B-GENE
+-	I-GENE
+A	I-GENE
+and	I-GENE
+B	I-GENE
+phenotypes	O
+of	O
+105	O
+patients	O
+suffering	O
+from	O
+malignant	O
+melanomas	O
+were	O
+determined	O
+,	O
+with	O
+special	O
+regard	O
+for	O
+metastatic	O
+form	O
+or	O
+relapse	O
+.	O
+
+Trypanosoma	O
+cruzi	O
+.	O
+
+The	O
+subjects	O
+of	O
+the	O
+study	O
+were	O
+10	O
+normal	O
+subjects	O
+and	O
+64	O
+patients	O
+with	O
+gastroduodenal	O
+disease	O
+.	O
+
+This	O
+study	O
+represents	O
+the	O
+first	O
+published	O
+long	O
+-	O
+term	O
+follow	O
+-	O
+up	O
+regarding	O
+this	O
+mode	O
+of	O
+treatment	O
+in	O
+patients	O
+with	O
+alveolar	O
+hypoventilation	O
+.	O
+
+A	O
+convenient	O
+measure	O
+of	O
+this	O
+impairment	O
+may	O
+be	O
+obtained	O
+using	O
+the	O
+ratio	O
+of	O
+urine	O
+volume	O
+(	O
+V	O
+)	O
+divided	O
+by	O
+lithium	O
+clearance	O
+(	O
+CLi	O
+)	O
+.	O
+
+Nitrogen	O
+balance	O
+was	O
+compared	O
+,	O
+and	O
+metabolic	O
+complications	O
+were	O
+monitored	O
+by	O
+evaluating	O
+BUN	O
+,	O
+serum	O
+creatinine	O
+,	O
+creatinine	O
+clearance	O
+,	O
+serum	O
+CO2	O
+,	O
+SGOT	B-GENE
+,	O
+SGPT	B-GENE
+,	O
+serum	B-GENE
+LDH	I-GENE
+,	O
+and	O
+serum	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+.	O
+
+Production	O
+of	O
+C	B-GENE
+mu	I-GENE
+RNAs	I-GENE
+,	O
+unlike	O
+mu	B-GENE
+mRNAs	I-GENE
+,	O
+does	O
+not	O
+require	O
+recombination	O
+with	O
+the	O
+joining	B-GENE
+region	I-GENE
+(	O
+JH	B-GENE
+)	O
+locus	O
+.	O
+
+The	O
+1	O
+.	O
+9	O
+-	O
+kb	O
+C	B-GENE
+mu	I-GENE
+RNA	O
+contains	O
+the	O
+3	O
+'	O
+sequence	O
+characteristic	O
+of	O
+secreted	O
+mu	B-GENE
+chain	I-GENE
+,	O
+whereas	O
+the	O
+longer	O
+species	O
+bear	O
+that	O
+of	O
+membrane	O
+-	O
+bound	O
+mu	B-GENE
+chin	O
+.	O
+
+Transcripts	O
+of	O
+the	O
+immunoglobulin	B-GENE
+C	I-GENE
+mu	I-GENE
+gene	I-GENE
+vary	O
+in	O
+structure	O
+and	O
+splicing	O
+during	O
+lymphoid	O
+development	O
+.	O
+
+Non	O
+-	O
+complement	O
+-	O
+dependent	O
+sperm	O
+-	O
+immobilizing	O
+activity	O
+was	O
+also	O
+detected	O
+in	O
+the	O
+cervical	O
+mucus	O
+of	O
+several	O
+patients	O
+.	O
+
+Although	O
+the	O
+mechanism	O
+of	O
+action	O
+of	O
+ICRF	O
+-	O
+159	O
+and	O
+187	O
+has	O
+not	O
+been	O
+clearly	O
+defined	O
+,	O
+it	O
+is	O
+evident	O
+from	O
+both	O
+preclinical	O
+and	O
+early	O
+clinical	O
+studies	O
+that	O
+these	O
+compounds	O
+are	O
+of	O
+interest	O
+.	O
+
+All	O
+62	O
+isolates	O
+were	O
+resistant	O
+to	O
+lincomycin	O
+,	O
+colistin	O
+,	O
+nystatin	O
+,	O
+amphotericin	O
+B	O
+,	O
+trimethoprim	O
+lactate	O
+,	O
+polymyxin	O
+B	O
+,	O
+and	O
+anisomycin	O
+.	O
+
+The	O
+evaluation	O
+of	O
+amniotic	O
+fluid	O
+delta	O
+OD450	O
+is	O
+considered	O
+to	O
+be	O
+the	O
+cornerstone	O
+of	O
+clinical	O
+management	O
+.	O
+
+Host	O
+lipids	O
+in	O
+tuberculous	O
+infection	O
+.	O
+
+The	O
+sympathetic	O
+neuroeffector	O
+influence	O
+on	O
+the	O
+myocardium	O
+with	O
+ATCI	O
+depends	O
+to	O
+a	O
+large	O
+measure	O
+on	O
+the	O
+intensity	O
+of	O
+the	O
+neurotransmitter	O
+biosynthesis	O
+and	O
+function	O
+of	O
+cardiomyocyte	O
+adrenoreceptors	O
+.	O
+
+Lens	B-GENE
+aldose	I-GENE
+reductase	I-GENE
+in	O
+diabetic	O
+and	O
+galactosemic	O
+cataracts	O
+.	O
+
+Fenfluramine	O
+(	O
+in	O
+doses	O
+ranging	O
+from	O
+0	O
+.	O
+0625	O
+-	O
+4	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+/	O
+infusion	O
+)	O
+did	O
+not	O
+maintain	O
+self	O
+-	O
+administration	O
+behavior	O
+at	O
+or	O
+above	O
+the	O
+minimum	O
+requirement	O
+(	O
+FR	O
+30	O
+)	O
+.	O
+
+In	O
+the	O
+course	O
+of	O
+Hepatitis	B-GENE
+A	I-GENE
+HBs	I-GENE
+-	I-GENE
+and	I-GENE
+HBe	I-GENE
+-	I-GENE
+antigen	I-GENE
+as	O
+well	O
+as	O
+HBc	B-GENE
+(	I-GENE
+IgM	I-GENE
+and	I-GENE
+IgG	I-GENE
+)	I-GENE
+-	I-GENE
+,	I-GENE
+HBs	I-GENE
+-	I-GENE
+and	I-GENE
+HBe	I-GENE
+-	I-GENE
+antibodies	I-GENE
+can	O
+be	O
+detected	O
+.	O
+
+The	O
+effect	O
+of	O
+the	O
+fatty	B-GENE
+acid	I-GENE
+cyclo	I-GENE
+-	I-GENE
+oxygenase	I-GENE
+inhibitor	O
+indomethacin	O
+on	O
+cerebral	O
+blood	O
+flow	O
+(	O
+CBF	O
+)	O
+and	O
+the	O
+metabolic	O
+rate	O
+for	O
+oxygen	O
+(	O
+CMRO2	O
+)	O
+was	O
+studied	O
+in	O
+paralyzed	O
+and	O
+artificially	O
+ventilated	O
+rats	O
+.	O
+
+The	O
+rat	O
+incisor	O
+is	O
+an	O
+excellent	O
+model	O
+system	O
+in	O
+which	O
+to	O
+study	O
+amelgenesis	O
+.	O
+
+The	O
+already	O
+elevated	O
+prolactin	B-GENE
+levels	O
+in	O
+nursing	O
+women	O
+were	O
+not	O
+influenced	O
+by	O
+chronic	O
+oestradiol	O
+administration	O
+.	O
+
+Morphine	O
+-	O
+dependent	O
+and	O
+control	O
+rats	O
+in	O
+an	O
+oral	O
+free	O
+-	O
+choice	O
+protocol	O
+were	O
+treated	O
+with	O
+gamma	O
+-	O
+vinyl	O
+GABA	O
+(	O
+GVG	O
+)	O
+,	O
+60	O
+,	O
+120	O
+and	O
+240	O
+mg	O
+/	O
+kg	O
+IP	O
+,	O
+for	O
+3	O
+days	O
+over	O
+three	O
+successive	O
+periods	O
+.	O
+
+Significance	O
+of	O
+the	O
+pulmonary	O
+gas	O
+exchange	O
+reaction	O
+to	O
+physical	O
+loading	O
+in	O
+evaluating	O
+the	O
+effectiveness	O
+of	O
+mitral	O
+commissurotomy	O
+
+Thyreoliberin	B-GENE
+VUFB	O
+in	O
+thyroid	O
+gammagraphy	O
+
+Advances	O
+in	O
+hemophilia	O
+treatment	O
+:	O
+a	O
+hepatitis	O
+-	O
+safe	O
+factor	B-GENE
+VIII	I-GENE
+concentrate	O
+
+This	O
+study	O
+was	O
+designed	O
+to	O
+assess	O
+and	O
+compare	O
+the	O
+ability	O
+of	O
+three	O
+different	O
+forms	O
+of	O
+DSG	O
+to	O
+block	O
+EIB	O
+.	O
+
+Comparison	O
+of	O
+three	O
+different	O
+preparations	O
+of	O
+disodium	O
+cromoglycate	O
+in	O
+the	O
+prevention	O
+of	O
+exercise	O
+-	O
+induced	O
+bronchospasm	O
+:	O
+a	O
+double	O
+-	O
+blind	O
+study	O
+.	O
+
+LCBF	O
+in	O
+normal	O
+and	O
+hypoxic	O
+puppies	O
+was	O
+correlated	O
+with	O
+local	O
+cerebral	O
+glucose	O
+utilization	O
+(	O
+LCGU	O
+)	O
+obtained	O
+under	O
+the	O
+same	O
+experimental	O
+conditions	O
+(	O
+Duffy	O
+et	O
+al	O
+,	O
+1982	O
+)	O
+.	O
+
+Phagocytosis	O
+of	O
+tubercle	O
+bacilli	O
+by	O
+macrophages	O
+.	O
+
+Detection	O
+of	O
+hemophilia	O
+A	O
+carriers	O
+.	O
+
+The	O
+stability	O
+of	O
+isoniazid	O
+solutions	O
+increases	O
+markedly	O
+with	O
+increasing	O
+NTA	O
+or	O
+EDTA	O
+concentration	O
+up	O
+to	O
+1	O
+mmol	O
+/	O
+l	O
+.	O
+
+Bile	O
+bilirubin	O
+did	O
+not	O
+rise	O
+within	O
+12	O
+h	O
+after	O
+haem	O
+infusion	O
+a	O
+finding	O
+which	O
+warrants	O
+further	O
+investigation	O
+.	O
+
+Autoimmune	O
+manipulation	O
+aids	O
+juvenile	O
+diabetes	O
+management	O
+.	O
+
+Other	O
+properties	O
+of	O
+Hg	O
+-	O
+and	O
+Cd	O
+-	O
+spores	O
+were	O
+similar	O
+to	O
+those	O
+of	O
+control	O
+spores	O
+.	O
+
+The	O
+decrease	O
+in	O
+HDL	B-GENE
+-	I-GENE
+cholesterol	I-GENE
+with	O
+increasing	O
+VLDL	B-GENE
+-	I-GENE
+triglycerides	I-GENE
+was	O
+relatively	O
+much	O
+larger	O
+than	O
+the	O
+concomitant	O
+decrease	O
+in	O
+apo	B-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+.	O
+
+Apo	B-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+level	O
+was	O
+unrelated	O
+to	O
+age	O
+,	O
+but	O
+increased	O
+with	O
+ethanol	O
+consumption	O
+and	O
+decreased	O
+with	O
+adiposity	O
+.	O
+
+The	O
+osmotic	O
+diuretic	O
+mannitol	O
+was	O
+administered	O
+to	O
+21	O
+patients	O
+.	O
+
+Of	O
+270	O
+patients	O
+with	O
+well	O
+-	O
+defined	O
+drug	O
+reactions	O
+,	O
+190	O
+(	O
+70	O
+per	O
+cent	O
+)	O
+gave	O
+a	O
+positive	O
+response	O
+to	O
+the	O
+mast	O
+cell	O
+test	O
+.	O
+
+Selenium	O
+,	O
+as	O
+a	O
+constituent	O
+of	O
+glutathione	B-GENE
+peroxidase	I-GENE
+,	O
+plays	O
+a	O
+role	O
+in	O
+the	O
+antioxidant	O
+defense	O
+systems	O
+of	O
+the	O
+body	O
+,	O
+but	O
+other	O
+metabolic	O
+roles	O
+for	O
+selenium	O
+may	O
+yet	O
+be	O
+discovered	O
+.	O
+
+Diagnostic	O
+value	O
+of	O
+serum	B-GENE
+myoglobin	I-GENE
+in	O
+cases	O
+of	O
+neuromuscular	O
+disease	O
+
+At	O
+43	O
+%	O
+blood	O
+pressure	O
+reduction	O
+,	O
+PCO2	O
+fell	O
+by	O
+0	O
+.	O
+53	O
+kPa	O
+,	O
+a	O
+decrease	O
+which	O
+could	O
+not	O
+explain	O
+the	O
+observed	O
+CBF	O
+fall	O
+of	O
+27	O
+%	O
+.	O
+
+During	O
+the	O
+last	O
+6	O
+months	O
+of	O
+the	O
+study	O
+a	O
+striking	O
+change	O
+in	O
+epidemiology	O
+concerning	O
+hepatitis	O
+A	O
+was	O
+seen	O
+,	O
+apparently	O
+caused	O
+by	O
+a	O
+steep	O
+increase	O
+in	O
+the	O
+incidence	O
+of	O
+this	O
+type	O
+of	O
+hepatitis	O
+among	O
+drug	O
+addicts	O
+.	O
+
+Asthmatic	O
+patients	O
+showed	O
+greater	O
+responses	O
+of	O
+both	O
+parameters	O
+to	O
+adrenaline	O
+than	O
+controls	O
+indicating	O
+that	O
+long	O
+-	O
+term	O
+corticosteroid	O
+treatment	O
+enhances	O
+the	O
+acute	O
+responses	O
+of	O
+plasminogen	B-GENE
+activator	I-GENE
+and	O
+clotting	B-GENE
+factor	I-GENE
+VIII	I-GENE
+to	O
+adrenaline	O
+infusion	O
+.	O
+
+Sulphur	O
+amino	O
+acids	O
+(	O
+g	O
+/	O
+16	O
+g	O
+N	O
+)	O
+were	O
+higher	O
+in	O
+the	O
+isolates	O
+than	O
+in	O
+the	O
+flours	O
+.	O
+
+Time	O
+shifts	O
+increase	O
+growth	B-GENE
+hormone	I-GENE
+release	O
+.	O
+
+It	O
+then	O
+merged	O
+with	O
+right	O
+ventricular	O
+wavefronts	O
+ending	O
+along	O
+the	O
+right	O
+ventricular	O
+anterior	O
+atrioventricular	O
+groove	O
+and	O
+outflow	O
+tract	O
+.	O
+
+Many	O
+of	O
+these	O
+landfill	O
+operations	O
+were	O
+undertaken	O
+in	O
+the	O
+early	O
+1950s	O
+and	O
+1960s	O
+,	O
+when	O
+knowledge	O
+regarding	O
+the	O
+safe	O
+and	O
+prolonged	O
+containment	O
+of	O
+the	O
+waste	O
+buried	O
+was	O
+nonexistent	O
+or	O
+minimal	O
+at	O
+best	O
+.	O
+
+Vesicles	O
+could	O
+be	O
+induced	O
+only	O
+with	O
+multiple	O
+exposures	O
+to	O
+UVA	O
+.	O
+
+The	O
+level	O
+of	O
+contamination	O
+in	O
+the	O
+wound	O
+can	O
+be	O
+determined	O
+with	O
+the	O
+rapid	O
+biopsy	O
+fixation	O
+technique	O
+.	O
+
+Self	O
+-	O
+heating	O
+after	O
+deep	O
+hypothermia	O
+(	O
+20	O
+degrees	O
+C	O
+)	O
+causes	O
+a	O
+considerable	O
+increase	O
+in	O
+the	O
+brain	O
+tissues	O
+glutaminase	B-GENE
+activity	O
+at	O
+all	O
+studied	O
+incubation	O
+temperatures	O
+(	O
+37	O
+,	O
+30	O
+,	O
+20	O
+and	O
+10	O
+degrees	O
+C	O
+)	O
+as	O
+compared	O
+to	O
+control	O
+rats	O
+and	O
+rats	O
+under	O
+hypothermia	O
+.	O
+
+According	O
+to	O
+Sugiura	O
+'	O
+s	O
+classification	O
+,	O
+they	O
+consisted	O
+of	O
+Type	O
+Ia	O
+in	O
+63	O
+%	O
+,	O
+Type	O
+Ib	O
+in	O
+11	O
+%	O
+,	O
+Type	O
+II	O
+in	O
+11	O
+%	O
+,	O
+and	O
+Type	O
+III	O
+in	O
+16	O
+%	O
+.	O
+
+This	O
+study	O
+was	O
+undertaken	O
+to	O
+define	O
+the	O
+mechanism	O
+for	O
+the	O
+respiratory	O
+inhibition	O
+observed	O
+during	O
+high	O
+-	O
+frequency	O
+oscillatory	O
+ventilation	O
+(	O
+HFOV	O
+)	O
+.	O
+
+Determination	O
+of	O
+20	O
+alpha	O
+-	O
+hydroxy	O
+-	O
+9	O
+beta	O
+,	O
+10	O
+alpha	O
+-	O
+pregna	O
+-	O
+4	O
+,	O
+6	O
+-	O
+dien	O
+-	O
+3	O
+-	O
+one	O
+in	O
+plasma	O
+by	O
+selected	O
+ion	O
+monitoring	O
+.	O
+
+A	O
+case	O
+of	O
+a	O
+dense	O
+epidermoid	O
+cyst	O
+of	O
+the	O
+suprasellar	O
+cistern	O
+is	O
+presented	O
+.	O
+
+Copper	O
+treatments	O
+were	O
+assigned	O
+to	O
+simulate	O
+the	O
+different	O
+levels	O
+of	O
+copper	O
+intake	O
+that	O
+might	O
+result	O
+from	O
+differences	O
+in	O
+daily	O
+feed	O
+intake	O
+similar	O
+to	O
+the	O
+practice	O
+followed	O
+with	O
+commercial	O
+industry	O
+.	O
+
+Because	O
+of	O
+a	O
+rapid	O
+development	O
+of	O
+the	O
+connective	O
+tissue	O
+scars	O
+,	O
+however	O
+,	O
+at	O
+the	O
+place	O
+of	O
+the	O
+destroyed	O
+glandular	O
+parenchyma	O
+areas	O
+,	O
+there	O
+is	O
+no	O
+normalization	O
+of	O
+the	O
+organ	O
+'	O
+s	O
+structure	O
+and	O
+function	O
+by	O
+the	O
+42d	O
+day	O
+.	O
+
+Histological	O
+signs	O
+of	O
+the	O
+flare	O
+-	O
+up	O
+reaction	O
+were	O
+already	O
+present	O
+at	O
+6	O
+hr	O
+after	O
+i	O
+.	O
+v	O
+.	O
+challenge	O
+and	O
+lasted	O
+for	O
+at	O
+least	O
+4	O
+days	O
+.	O
+
+Significant	O
+GMBF	O
+reductions	O
+occurred	O
+in	O
+early	O
+shock	O
+in	O
+both	O
+treatment	O
+groups	O
+.	O
+
+Of	O
+254	O
+children	O
+with	O
+neuroblastoma	O
+treated	O
+at	O
+St	O
+.	O
+
+Penicillin	O
+-	O
+G	O
+degradation	O
+products	O
+inhibit	O
+in	O
+vitro	O
+granulopoiesis	O
+.	O
+
+Plasma	O
+fibrinogen	B-GENE
+was	O
+measured	O
+by	O
+the	O
+turbidimetric	O
+method	O
+in	O
+timol	O
+turbidimetric	O
+units	O
+.	O
+
+Five	O
+patients	O
+with	O
+type	O
+III	O
+musculoskeletal	O
+infection	O
+from	O
+nongonococcal	O
+Neisseria	O
+species	O
+were	O
+examined	O
+during	O
+a	O
+13	O
+-	O
+month	O
+period	O
+.	O
+
+Distal	O
+tubular	O
+acidification	O
+and	O
+the	O
+threshold	O
+for	O
+proximal	O
+tubular	O
+bicarbonate	O
+reabsorption	O
+were	O
+normal	O
+,	O
+as	O
+was	O
+urine	O
+concentrating	O
+capacity	O
+.	O
+
+The	O
+Tullio	O
+phenomenon	O
+,	O
+fistula	O
+test	O
+,	O
+and	O
+Hennebert	O
+'	O
+s	O
+sign	O
+:	O
+clinical	O
+significance	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+significant	O
+pulmonary	O
+metabolism	O
+of	O
+5	O
+-	O
+HT	O
+followed	O
+by	O
+efflux	O
+of	O
+5	O
+-	O
+HIAA	O
+into	O
+venous	O
+output	O
+occurs	O
+during	O
+single	O
+-	O
+pass	O
+circulation	O
+.	O
+
+Disturbances	O
+of	O
+placental	O
+maturation	O
+,	O
+2	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+histopathological	O
+findings	O
+,	O
+the	O
+origin	O
+of	O
+amyloid	O
+appeared	O
+to	O
+be	O
+closely	O
+related	O
+to	O
+the	O
+fibroblasts	O
+.	O
+
+Serum	O
+lactate	B-GENE
+dehydrogenase	I-GENE
+and	O
+haptoglobin	B-GENE
+levels	O
+were	O
+normal	O
+,	O
+and	O
+total	O
+bilirubin	O
+was	O
+only	O
+slightly	O
+elevated	O
+.	O
+
+Low	O
+-	O
+dose	O
+D	O
+(	O
+0	O
+.	O
+4	O
+-	O
+0	O
+.	O
+8	O
+mg	O
+)	O
+and	O
+DB	O
+(	O
+1	O
+.	O
+0	O
+-	O
+5	O
+.	O
+0	O
+mg	O
+)	O
+did	O
+not	O
+significantly	O
+alter	O
+any	O
+parameter	O
+from	O
+control	O
+.	O
+
+Leads	O
+from	O
+the	O
+MMWR	O
+.	O
+
+The	O
+presence	O
+of	O
+visna	O
+-	O
+maedi	O
+in	O
+Italy	O
+is	O
+reported	O
+for	O
+the	O
+first	O
+time	O
+.	O
+
+High	O
+levels	O
+of	O
+IC	O
+coincided	O
+with	O
+relative	O
+hypocomplementemia	O
+.	O
+
+Acute	O
+type	O
+A	O
+hepatitis	O
+in	O
+three	O
+patients	O
+with	O
+chronic	O
+HBV	O
+infection	O
+.	O
+
+Pathogenetic	O
+relationships	O
+between	O
+renal	O
+tubular	O
+acidosis	O
+and	O
+sodium	O
+metabolism	O
+alterations	O
+in	O
+liver	O
+cirrhosis	O
+.	O
+
+5	O
+microU	O
+/	O
+l	O
+thyrotropin	B-GENE
+:	O
+75	O
+%	O
+(	O
+1974	O
+)	O
+,	O
+45	O
+%	O
+(	O
+1977	O
+)	O
+and	O
+20	O
+%	O
+(	O
+1980	O
+)	O
+.	O
+
+Echosismography	O
+enables	O
+to	O
+improve	O
+the	O
+diagnosis	O
+when	O
+compared	O
+with	O
+classical	O
+sonography	O
+in	O
+about	O
+20	O
+%	O
+of	O
+cases	O
+.	O
+
+Relationships	O
+with	O
+the	O
+acquired	O
+immune	O
+deficiency	O
+syndrome	O
+.	O
+
+The	O
+prevalence	O
+of	O
+CPAF	O
+was	O
+similar	O
+in	O
+type	O
+1	O
+and	O
+type	O
+2	O
+diabetes	O
+,	O
+was	O
+greater	O
+in	O
+women	O
+than	O
+in	O
+men	O
+,	O
+and	O
+was	O
+significantly	O
+greater	O
+after	O
+repeated	O
+administrations	O
+than	O
+after	O
+one	O
+single	O
+administration	O
+of	O
+chlorpropamide	O
+.	O
+
+A	O
+reassessment	O
+of	O
+the	O
+prevalence	O
+data	O
+was	O
+carried	O
+out	O
+in	O
+the	O
+southern	O
+province	O
+of	O
+Uusimaa	O
+and	O
+in	O
+the	O
+western	O
+province	O
+of	O
+Vaasa	O
+,	O
+the	O
+prevalence	O
+day	O
+being	O
+January	O
+1	O
+,	O
+1979	O
+.	O
+
+The	O
+results	O
+confirm	O
+and	O
+extend	O
+previous	O
+work	O
+by	O
+other	O
+researchers	O
+.	O
+
+In	O
+patients	O
+with	O
+complete	O
+or	O
+partial	O
+remission	O
+of	O
+the	O
+tumor	O
+,	O
+the	O
+neopterine	O
+excretion	O
+dropped	O
+to	O
+normal	O
+values	O
+.	O
+
+In	O
+visible	O
+tumours	O
+the	O
+best	O
+results	O
+were	O
+obtained	O
+with	O
+FB	O
+(	O
+85	O
+%	O
+)	O
+while	O
+TBN	O
+was	O
+positive	O
+in	O
+65	O
+%	O
+.	O
+
+Total	O
+PGE	O
+levels	O
+in	O
+synovial	O
+fluid	O
+remained	O
+significantly	O
+depressed	O
+in	O
+the	O
+patient	O
+group	O
+for	O
+24	O
+hours	O
+after	O
+the	O
+400	O
+-	O
+mg	O
+test	O
+dose	O
+of	O
+tolmetin	O
+on	O
+day	O
+8	O
+.	O
+
+Normal	O
+rates	O
+of	O
+weight	O
+gain	O
+were	O
+seen	O
+once	O
+absorbed	O
+energy	O
+intakes	O
+reached	O
+100	O
+-	O
+110	O
+%	O
+of	O
+requirements	O
+.	O
+
+Its	O
+vasodilatory	O
+,	O
+anti	O
+-	O
+vasopressor	O
+,	O
+and	O
+platelet	O
+stabilizing	O
+effects	O
+could	O
+be	O
+expected	O
+to	O
+counteract	O
+the	O
+placental	O
+ischemia	O
+,	O
+hypertension	O
+and	O
+excessive	O
+coagulation	O
+that	O
+are	O
+seen	O
+in	O
+pre	O
+-	O
+eclampsia	O
+.	O
+
+Behcet	O
+'	O
+s	O
+syndrome	O
+
+Survival	O
+of	O
+111	O
+Indium	O
+-	O
+labelled	O
+autologous	O
+platelets	O
+was	O
+studied	O
+in	O
+2	O
+patients	O
+after	O
+correction	O
+of	O
+platelet	O
+count	O
+and	O
+was	O
+still	O
+found	O
+shortened	O
+.	O
+
+The	O
+effect	O
+of	O
+emotional	O
+-	O
+painful	O
+stress	O
+(	O
+EPS	O
+)	O
+on	O
+myocardial	O
+extensibility	O
+and	O
+contractility	O
+was	O
+studied	O
+on	O
+an	O
+isolated	O
+rat	O
+atrium	O
+.	O
+
+When	O
+O2	O
+therapy	O
+was	O
+controlled	O
+for	O
+,	O
+the	O
+association	O
+between	O
+RBT	O
+and	O
+RLF	O
+did	O
+not	O
+achieve	O
+statistical	O
+significance	O
+(	O
+P	O
+=	O
+.	O
+07	O
+)	O
+.	O
+
+This	O
+two	O
+-	O
+helix	O
+motif	O
+is	O
+thought	O
+to	O
+be	O
+involved	O
+in	O
+specific	O
+DNA	O
+sequence	O
+recognition	O
+by	O
+CAP	B-GENE
+.	O
+
+Statistics	O
+for	O
+nurse	O
+managers	O
+-	O
+-	O
+3	O
+.	O
+
+The	O
+infection	O
+rate	O
+was	O
+five	O
+times	O
+greater	O
+in	O
+patients	O
+with	O
+Hickman	O
+catheters	O
+than	O
+in	O
+those	O
+with	O
+Broviac	O
+catheters	O
+(	O
+p	O
+=	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Setting	O
+takes	O
+place	O
+through	O
+complex	O
+formation	O
+of	O
+(	O
+NH4Mg	O
+PO4	O
+.	O
+6H2O	O
+)	O
+n	O
+,	O
+excess	O
+reactants	O
+,	O
+and	O
+water	O
+.	O
+
+Serum	B-GENE
+IgE	I-GENE
+levels	O
+in	O
+Tauranga	O
+children	O
+.	O
+
+Use	O
+of	O
+prostaglandin	O
+F2	O
+alpha	O
+(	O
+PGF2	O
+alpha	O
+)	O
+in	O
+cattle	O
+breeding	O
+.	O
+
+Thus	O
+it	O
+appears	O
+that	O
+the	O
+management	O
+of	O
+blood	O
+,	O
+including	O
+washing	O
+is	O
+of	O
+great	O
+importance	O
+.	O
+
+Range	O
+,	O
+variations	O
+and	O
+neoplastic	O
+potential	O
+.	O
+
+The	O
+scores	O
+are	O
+dependent	O
+in	O
+part	O
+on	O
+the	O
+reliability	O
+of	O
+faculty	O
+evaluations	O
+.	O
+
+Study	O
+on	O
+distribution	O
+of	O
+metal	O
+in	O
+the	O
+teeth	O
+treated	O
+by	O
+iontophoresis	O
+with	O
+transparent	O
+specimens	O
+
+Whereas	O
+creatine	B-GENE
+kinase	I-GENE
+activity	O
+declined	O
+exponentially	O
+from	O
+a	O
+single	O
+peak	O
+,	O
+myoglobin	B-GENE
+appeared	O
+in	O
+multiple	O
+episodes	O
+inadequately	O
+represented	O
+by	O
+a	O
+single	O
+peak	O
+value	O
+and	O
+having	O
+no	O
+clear	O
+clinical	O
+correlation	O
+.	O
+
+Utero	O
+-	O
+placental	O
+blood	O
+flow	O
+and	O
+the	O
+effect	O
+of	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+stimulating	O
+drugs	O
+.	O
+
+Development	O
+of	O
+basophilic	O
+leukemia	O
+with	O
+trisomy	O
+8	O
+and	O
+atypical	O
+erythroblastosis	O
+in	O
+a	O
+patient	O
+with	O
+a	O
+history	O
+of	O
+aplastic	O
+anemia	O
+22	O
+years	O
+earlier	O
+
+The	O
+arginyl	O
+peptide	O
+bonds	O
+that	O
+are	O
+cleaved	O
+in	O
+the	O
+conversion	O
+of	O
+human	B-GENE
+factor	I-GENE
+IX	I-GENE
+to	O
+factor	B-GENE
+IXa	I-GENE
+by	O
+factor	B-GENE
+XIa	I-GENE
+were	O
+identified	O
+as	O
+Arg145	O
+-	O
+Ala146	O
+and	O
+Arg180	O
+-	O
+Val181	O
+.	O
+
+Alveolar	O
+growth	O
+,	O
+contemporary	O
+with	O
+dental	O
+eruption	O
+,	O
+is	O
+sufficient	O
+to	O
+compensate	O
+possible	O
+hypotrophy	O
+of	O
+maxillary	O
+bone	O
+bases	O
+.	O
+
+Renal	O
+and	O
+extrarenal	O
+arterial	O
+fibromuscular	O
+hyperplasia	O
+with	O
+hypertension	O
+.	O
+
+Both	O
+examinations	O
+are	O
+sensitive	O
+indicators	O
+of	O
+CNS	O
+abnormalities	O
+associated	O
+with	O
+bacterial	O
+meningeal	O
+infections	O
+and	O
+are	O
+important	O
+determinants	O
+of	O
+the	O
+therapy	O
+and	O
+ultimate	O
+prognosis	O
+of	O
+such	O
+complications	O
+.	O
+
+Similar	O
+clinical	O
+evaluation	O
+of	O
+an	O
+obligate	O
+carrier	O
+revealed	O
+no	O
+ocular	O
+abnormalities	O
+.	O
+
+A	O
+case	O
+of	O
+anterior	O
+cleavage	O
+syndrome	O
+in	O
+a	O
+27	O
+-	O
+year	O
+-	O
+old	O
+female	O
+patient	O
+is	O
+described	O
+.	O
+
+The	O
+daily	O
+administration	O
+of	O
+betamethasone	O
+for	O
+three	O
+weeks	O
+markedly	O
+reduced	O
+the	O
+absorption	O
+of	O
+calcium	O
+and	O
+phosphate	O
+as	O
+well	O
+as	O
+the	O
+growth	O
+rate	O
+.	O
+
+Endorphins	B-GENE
+and	O
+legal	O
+issues	O
+.	O
+
+At	O
+necropsy	O
+28	O
+days	O
+post	O
+-	O
+inoculation	O
+,	O
+F344	O
+rats	O
+had	O
+no	O
+gross	O
+lung	O
+lesions	O
+,	O
+even	O
+those	O
+given	O
+the	O
+maximum	O
+dose	O
+of	O
+1	O
+.	O
+4	O
+X	O
+10	O
+(	O
+9	O
+)	O
+colony	O
+-	O
+forming	O
+units	O
+of	O
+M	O
+.	O
+pulmonis	O
+.	O
+
+Aneurysmectomy	O
+and	O
+the	O
+performance	O
+of	O
+CABG	O
+were	O
+not	O
+significantly	O
+associated	O
+with	O
+postoperative	O
+ECG	O
+changes	O
+,	O
+but	O
+more	O
+bypass	O
+grafts	O
+per	O
+patient	O
+grafted	O
+appeared	O
+in	O
+the	O
+group	O
+with	O
+postoperative	O
+ECG	O
+changes	O
+,	O
+suggesting	O
+that	O
+coronary	O
+artery	O
+disease	O
+may	O
+be	O
+more	O
+severe	O
+in	O
+that	O
+group	O
+.	O
+
+REV	O
+I	O
+:	O
+All	O
+vessels	O
+up	O
+to	O
+50	O
+%	O
+stenosed	O
+have	O
+a	O
+patent	O
+graft	O
+.	O
+
+Complete	O
+sequences	O
+were	O
+obtained	O
+for	O
+the	O
+three	O
+large	O
+thrombic	O
+peptides	O
+,	O
+and	O
+these	O
+were	O
+aligned	O
+by	O
+using	O
+peptides	O
+from	O
+the	O
+V8	B-GENE
+protease	I-GENE
+digest	O
+.	O
+
+The	O
+extraction	O
+measurements	O
+were	O
+used	O
+to	O
+test	O
+for	O
+extracerebral	O
+contamination	O
+of	O
+venous	O
+outflow	O
+.	O
+
+Contractile	O
+responses	O
+to	O
+norepinephrine	O
+,	O
+serotonin	O
+and	O
+potassium	O
+(	O
+K	O
++	O
+)	O
+and	O
+relaxant	O
+responses	O
+to	O
+isoproterenol	O
+and	O
+papaverine	O
+were	O
+studied	O
+in	O
+vitro	O
+with	O
+spirally	O
+cut	O
+thoracic	O
+aortic	O
+strips	O
+from	O
+aortic	O
+coarcted	O
+hypertensive	O
+rats	O
+(	O
+AHR	O
+)	O
+2	O
+,	O
+6	O
+,	O
+14	O
+and	O
+28	O
+days	O
+postoperatively	O
+and	O
+compared	O
+to	O
+time	O
+-	O
+matched	O
+,	O
+sham	O
+-	O
+operated	O
+normotensive	O
+controls	O
+.	O
+
+On	O
+line	O
+calculation	O
+of	O
+steroid	O
+concentrations	O
+by	O
+radioimmunoassay	O
+
+Detection	O
+of	O
+congenital	O
+hypothyroidism	O
+in	O
+26	O
+,	O
+282	O
+newborn	O
+infants	O
+
+In	O
+rubella	O
+patients	O
+with	O
+serologic	O
+confirmation	O
+by	O
+HI	O
+,	O
+the	O
+IF	O
+test	O
+detected	O
+significant	O
+rises	O
+in	O
+219	O
+(	O
+99	O
+.	O
+1	O
+%	O
+)	O
+of	O
+221	O
+patients	O
+and	O
+the	O
+PHA	B-GENE
+test	O
+detected	O
+antibody	O
+conversion	O
+in	O
+68	O
+(	O
+93	O
+%	O
+)	O
+of	O
+73	O
+patients	O
+.	O
+
+The	O
+effect	O
+of	O
+sodium	O
+saccharin	O
+in	O
+the	O
+diet	O
+on	O
+caecal	O
+microflora	O
+.	O
+
+The	O
+residue	O
+functions	O
+,	O
+R	O
+(	O
+t	O
+)	O
+,	O
+for	O
+C	O
+-	O
+11	O
+CPZ	O
+and	O
+In	O
+-	O
+113m	O
+transferrin	B-GENE
+were	O
+plotted	O
+against	O
+time	O
+for	O
+selected	O
+areas	O
+of	O
+interest	O
+,	O
+and	O
+the	O
+CPZ	O
+area	O
+-	O
+weighted	O
+extraction	O
+,	O
+E	O
+(	O
+t	O
+)	O
+,	O
+was	O
+computed	O
+for	O
+the	O
+same	O
+areas	O
+every	O
+250	O
+msec	O
+using	O
+the	O
+formula	O
+:	O
+E	O
+(	O
+t	O
+)	O
+=	O
+[	O
+RT	O
+(	O
+t	O
+)	O
+-	O
+RR	O
+(	O
+t	O
+)	O
+]	O
+/	O
+[	O
+1	O
+-	O
+RR	O
+(	O
+t	O
+)	O
+]	O
+,	O
+where	O
+RT	O
+and	O
+RR	O
+are	O
+the	O
+normalized	O
+residue	O
+functions	O
+for	O
+CPZ	O
+and	O
+transferrin	B-GENE
+,	O
+respectively	O
+.	O
+
+Synchronous	O
+extracts	O
+showed	O
+no	O
+significant	O
+migration	O
+inhibition	O
+in	O
+allogeneic	O
+assays	O
+.	O
+
+Ten	O
+days	O
+of	O
+cefadroxil	O
+therapy	O
+was	O
+used	O
+to	O
+treat	O
+44	O
+children	O
+with	O
+urinary	O
+tract	O
+infection	O
+and	O
+CRP	B-GENE
+values	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+28	O
+microgram	O
+/	O
+ml	O
+(	O
+CRP	B-GENE
+-	O
+positive	O
+group	O
+)	O
+.	O
+
+Both	O
+resting	O
+blood	O
+flow	O
+(	O
+RBF	O
+)	O
+and	O
+maximal	O
+blood	O
+flow	O
+(	O
+NBF	O
+)	O
+were	O
+studied	O
+by	O
+Xenon	O
+133	O
+clearance	O
+.	O
+
+Plasma	B-GENE
+renin	I-GENE
+concentration	O
+is	O
+significantly	O
+higher	O
+in	O
+the	O
+subcapsular	O
+venous	O
+outflow	O
+,	O
+which	O
+drains	O
+the	O
+superficial	O
+cortex	O
+,	O
+than	O
+in	O
+the	O
+deep	O
+venous	O
+outflow	O
+,	O
+which	O
+drains	O
+the	O
+inner	O
+half	O
+of	O
+the	O
+cortex	O
+and	O
+medulla	O
+of	O
+the	O
+cat	O
+kidney	O
+.	O
+
+After	O
+acclimation	O
+,	O
+resting	O
+supine	O
+and	O
+sitting	O
+DPB	O
+decreased	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+by	O
+6	O
+and	O
+9	O
+mmHg	O
+,	O
+respectively	O
+.	O
+
+In	O
+the	O
+diabetics	O
+,	O
+Ca2	O
++	O
+infusions	O
+induced	O
+a	O
+rise	O
+of	O
+plasma	O
+Ca2	O
++	O
+up	O
+to	O
+3	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+1	O
+mmol	O
+/	O
+1	O
+and	O
+a	O
+fall	O
+of	O
+circulating	O
+glucagon	B-GENE
+(	O
+-	O
+26	O
+.	O
+4	O
++	O
+/	O
+-	O
+5	O
+.	O
+7	O
+%	O
+;	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+and	O
+glucose	O
+(	O
+-	O
+23	O
+.	O
+3	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+%	O
+;	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Fifty	O
+-	O
+eight	O
+RMI	O
+'	O
+s	O
+occurred	O
+in	O
+the	O
+placebo	O
+group	O
+as	O
+compared	O
+to	O
+only	O
+twenty	O
+in	O
+the	O
+AC	O
+group	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+All	O
+patients	O
+in	O
+the	O
+control	O
+group	O
+showed	O
+a	O
+significant	O
+improvement	O
+in	O
+their	O
+PEFR	O
+while	O
+only	O
+3	O
+patients	O
+in	O
+the	O
+treated	O
+group	O
+showed	O
+an	O
+improvement	O
+.	O
+
+Facts	O
+on	O
+the	O
+Economic	O
+Recovery	O
+Tax	O
+Act	O
+of	O
+1981	O
+for	O
+speech	O
+-	O
+language	O
+pathologists	O
+and	O
+audiologists	O
+.	O
+
+From	O
+Pap	O
+to	O
+ApUp	O
+.	O
+
+The	O
+relationship	O
+between	O
+the	O
+rare	O
+complications	O
+mentioned	O
+above	O
+and	O
+the	O
+pathophysiology	O
+of	O
+Bartter	O
+'	O
+s	O
+syndrome	O
+is	O
+still	O
+obscure	O
+.	O
+
+Using	O
+an	O
+opsonophagocytic	O
+bacterial	O
+assay	O
+and	O
+a	O
+suckling	O
+rat	O
+model	O
+of	O
+GBS	O
+sepsis	O
+,	O
+we	O
+analyzed	O
+a	O
+modified	O
+human	B-GENE
+immunoglobulin	I-GENE
+for	O
+opsonic	O
+and	O
+protective	O
+antibody	O
+.	O
+
+Glomerular	O
+lesions	O
+in	O
+renal	O
+allografts	O
+.	O
+
+Commonly	O
+observed	O
+systemic	O
+toxic	O
+effects	O
+(	O
+bone	O
+marrow	O
+,	O
+gastrointestinal	O
+tract	O
+,	O
+and	O
+heart	O
+)	O
+were	O
+not	O
+seen	O
+in	O
+this	O
+study	O
+.	O
+
+2	O
+.	O
+
+When	O
+vascular	O
+pressure	O
+(	O
+Pvas	O
+)	O
+was	O
+raised	O
+abruptly	O
+from	O
+-	O
+5	O
+to	O
++	O
+25	O
+cmH2O	O
+by	O
+air	O
+inflation	O
+for	O
+60	O
+min	O
+,	O
+Px	O
+(	O
+f	O
+)	O
+became	O
+abruptly	O
+less	O
+negative	O
+,	O
+then	O
+remained	O
+stable	O
+.	O
+
+(	O
+1980	O
+)	O
+:	O
+Science	O
+210	O
+,	O
+77	O
+-	O
+72	O
+)	O
+that	O
+stimulating	O
+the	O
+crossed	O
+olivocochlear	O
+bundle	O
+(	O
+COCB	O
+)	O
+can	O
+change	O
+the	O
+magnitude	O
+of	O
+the	O
+distortion	O
+product	O
+(	O
+f2	O
+-	O
+f1	O
+)	O
+in	O
+the	O
+ear	O
+-	O
+canal	O
+sound	O
+pressure	O
+.	O
+
+Rats	O
+underwent	O
+either	O
+a	O
+90	O
+-	O
+95	O
+%	O
+JIB	O
+or	O
+a	O
+sham	O
+operation	O
+.	O
+
+When	O
+the	O
+l	O
+-	O
+methadone	O
+-	O
+sensitive	O
+,	O
+opioid	B-GENE
+receptor	I-GENE
+is	O
+blocked	O
+by	O
+naloxone	O
+or	O
+tolerance	O
+has	O
+developed	O
+,	O
+than	O
+l	O
+-	O
+methadone	O
+can	O
+produce	O
+behavioral	O
+effects	O
+by	O
+a	O
+nonopioid	O
+mechanism	O
+.	O
+
+Microwave	O
+hyperthermia	O
+-	O
+induced	O
+blood	O
+-	O
+brain	O
+barrier	O
+alterations	O
+.	O
+
+Large	O
+and	O
+small	O
+medullary	O
+lesions	O
+inhibited	O
+the	O
+occurrence	O
+of	O
+target	O
+fibres	O
+in	O
+the	O
+tenotomized	O
+muscles	O
+,	O
+the	O
+smallest	O
+one	O
+being	O
+neurolysis	O
+of	O
+the	O
+dorsal	O
+roots	O
+.	O
+
+In	O
+10	O
+control	O
+sheep	O
+mean	O
+plasma	O
+TXB2	O
+concentration	O
+increased	O
+from	O
+0	O
+.	O
+39	O
+ng	O
+/	O
+ml	O
+prebypass	O
+to	O
+about	O
+1	O
+.	O
+1	O
+ng	O
+/	O
+ml	O
+at	O
+8	O
+and	O
+16	O
+min	O
+of	O
+bypass	O
+.	O
+
+The	O
+respiratory	O
+rate	O
+was	O
+13	O
++	O
+/	O
+-	O
+1	O
+breaths	O
+/	O
+min	O
+with	O
+52	O
++	O
+/	O
+-	O
+4	O
+%	O
+of	O
+the	O
+respiratory	O
+cycle	O
+spent	O
+in	O
+inspiration	O
+;	O
+end	O
+-	O
+tidal	O
+CO2	O
+pressure	O
+increased	O
+by	O
+3	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+Torr	O
+during	O
+runs	O
+at	O
+SIP	O
+.	O
+
+There	O
+was	O
+no	O
+further	O
+increase	O
+in	O
+oxygen	O
+consumption	O
+when	O
+these	O
+subjects	O
+breathed	O
+with	O
+inspiratory	O
+pressures	O
+above	O
+SIP	O
+.	O
+
+We	O
+compared	O
+the	O
+volume	O
+of	O
+the	O
+pulmonary	O
+extravascular	O
+,	O
+extracellular	O
+water	O
+space	O
+using	O
+sodium	O
+and	O
+sucrose	O
+indicators	O
+in	O
+8	O
+normal	O
+and	O
+11	O
+edematous	O
+rabbit	O
+lungs	O
+by	O
+steady	O
+-	O
+state	O
+techniques	O
+.	O
+
+Investigated	O
+the	O
+reliability	O
+,	O
+validity	O
+and	O
+dimensionality	O
+of	O
+scores	O
+obtained	O
+by	O
+acute	O
+psychiatric	O
+inpatients	O
+(	O
+N	O
+=	O
+120	O
+)	O
+on	O
+the	O
+Michigan	O
+Alcoholism	O
+Screening	O
+Test	O
+adapted	O
+to	O
+assess	O
+lifetime	O
+and	O
+current	O
+symptomatology	O
+.	O
+
+A	O
+simple	O
+method	O
+for	O
+measuring	O
+urinary	O
+iron	O
+following	O
+the	O
+administration	O
+of	O
+desferrioxamine	O
+(	O
+DF	O
+)	O
+is	O
+described	O
+.	O
+
+During	O
+conventional	O
+hemofiltration	O
+using	O
+substitution	O
+fluid	O
+with	O
+a	O
+Na	O
++	O
+concentration	O
+of	O
+140	O
+mEq	O
+/	O
+L	O
+,	O
+a	O
+decrease	O
+in	O
+extracellular	O
+fluid	O
+volume	O
+was	O
+noted	O
+whereas	O
+the	O
+intracellular	O
+fluid	O
+volume	O
+was	O
+unaltered	O
+.	O
+
+Transvenous	O
+serial	O
+xeroradiography	O
+.	O
+
+Recommendations	O
+to	O
+deal	O
+with	O
+these	O
+and	O
+related	O
+issues	O
+are	O
+presented	O
+.	O
+
+Use	O
+of	O
+subcutaneous	O
+deferoxamine	O
+in	O
+a	O
+child	O
+with	O
+hemochromatosis	O
+associated	O
+with	O
+congenital	O
+dyserythropoietic	O
+anemia	O
+,	O
+type	O
+I	O
+.	O
+
+Although	O
+noninhibitory	O
+fluid	O
+had	O
+higher	O
+mean	O
+concentrations	O
+of	O
+phosphorus	O
+and	O
+zinc	O
+,	O
+these	O
+differences	O
+did	O
+not	O
+hold	O
+after	O
+meconium	O
+-	O
+stained	O
+samples	O
+were	O
+excluded	O
+.	O
+
+Selenium	O
+status	O
+of	O
+thoroughbreds	O
+in	O
+the	O
+United	O
+Kingdom	O
+.	O
+
+During	O
+an	O
+8	O
+-	O
+wk	O
+follow	O
+-	O
+up	O
+,	O
+parasites	O
+reappeared	O
+in	O
+10	O
+patients	O
+,	O
+5	O
+after	O
+each	O
+drug	O
+,	O
+between	O
+1	O
+and	O
+7	O
+wk	O
+after	O
+treatment	O
+.	O
+
+Preparation	O
+of	O
+a	O
+stable	O
+phospholipid	O
+reagent	O
+for	O
+coagulation	O
+assays	O
+.	O
+
+Before	O
+turnout	O
+,	O
+a	O
+morantel	O
+sustained	O
+release	O
+bolus	O
+(	O
+MSRB	O
+)	O
+was	O
+administered	O
+to	O
+each	O
+animal	O
+in	O
+the	O
+"	O
+treated	O
+"	O
+category	O
+.	O
+
+In	O
+a	O
+longitudinal	O
+study	O
+,	O
+14	O
+low	O
+-	O
+risk	O
+fetuses	O
+were	O
+studied	O
+at	O
+2	O
+-	O
+week	O
+intervals	O
+from	O
+32	O
+weeks	O
+of	O
+gestation	O
+onward	O
+.	O
+
+Further	O
+,	O
+intracerebroventricular	O
+injections	O
+of	O
+KA	O
+resulted	O
+in	O
+the	O
+substantial	O
+loss	O
+of	O
+pyramidal	O
+cells	O
+in	O
+the	O
+whole	O
+CA3	O
+field	O
+of	O
+the	O
+hippocampus	O
+.	O
+
+Seventeen	O
+of	O
+the	O
+35	O
+patients	O
+were	O
+randomly	O
+chosen	O
+to	O
+receive	O
+a	O
+training	O
+program	O
+(	O
+lasting	O
+approximately	O
+1	O
+month	O
+)	O
+designed	O
+to	O
+establish	O
+a	O
+systematic	O
+strategy	O
+of	O
+organizing	O
+complex	O
+visual	O
+material	O
+.	O
+
+The	O
+duration	O
+and	O
+the	O
+amplitude	O
+of	O
+the	O
+negative	O
+potential	O
+were	O
+greatest	O
+for	O
+completely	O
+regenerating	O
+ears	O
+with	O
+overgrowth	O
+,	O
+smaller	O
+for	O
+partially	O
+regenerating	O
+ears	O
+,	O
+and	O
+smallest	O
+for	O
+the	O
+nonregenerating	O
+ears	O
+.	O
+
+Samples	O
+obtained	O
+from	O
+normal	O
+volunteers	O
+and	O
+from	O
+the	O
+great	O
+majority	O
+of	O
+the	O
+patients	O
+,	O
+excluding	O
+those	O
+with	O
+asthma	O
+,	O
+had	O
+no	O
+effect	O
+on	O
+ciliary	O
+beating	O
+.	O
+
+These	O
+results	O
+suggested	O
+the	O
+possibility	O
+that	O
+the	O
+fetus	O
+played	O
+some	O
+role	O
+in	O
+the	O
+production	O
+of	O
+E3	O
+-	O
+16	O
+-	O
+G	O
+in	O
+early	O
+pregnancy	O
+.	O
+
+In	O
+this	O
+way	O
+it	O
+is	O
+possible	O
+to	O
+simulate	O
+the	O
+growth	O
+function	O
+of	O
+the	O
+embryofetal	O
+curve	O
+of	O
+the	O
+length	O
+'	O
+increase	O
+of	O
+man	O
+and	O
+the	O
+curve	O
+of	O
+the	O
+mass	O
+'	O
+increase	O
+of	O
+rat	O
+.	O
+
+The	O
+highest	O
+doses	O
+were	O
+found	O
+for	O
+drivers	O
+who	O
+transported	O
+large	O
+numbers	O
+of	O
+99Mo	O
+generators	O
+.	O
+
+The	O
+steepness	O
+of	O
+the	O
+standard	O
+O2	O
+dissociation	O
+curve	O
+becomes	O
+greater	O
+during	O
+the	O
+training	O
+period	O
+(	O
+increase	O
+in	O
+Hill	O
+'	O
+s	O
+n	O
+from	O
+2	O
+.	O
+68	O
++	O
+/	O
+-	O
+0	O
+.	O
+10	O
+to	O
+2	O
+.	O
+96	O
++	O
+/	O
+-	O
+0	O
+.	O
+15	O
+)	O
+.	O
+
+Conjugated	O
+and	O
+unconjugated	O
+phenylacetic	O
+acid	O
+and	O
+m	O
+-	O
+and	O
+p	O
+-	O
+hydroxyphenylacetic	O
+acid	O
+have	O
+been	O
+determined	O
+in	O
+the	O
+plasma	O
+of	O
+normal	O
+,	O
+healthy	O
+subjects	O
+after	O
+fasting	O
+,	O
+consumption	O
+of	O
+a	O
+meal	O
+and	O
+ingestion	O
+of	O
+deuterium	O
+labelled	O
+amine	O
+precursors	O
+,	O
+by	O
+high	O
+-	O
+resolution	O
+gas	O
+chromatography	O
+-	O
+-	O
+high	O
+resolution	O
+mass	O
+spectrometry	O
+with	O
+selected	O
+ion	O
+monitoring	O
+of	O
+their	O
+trifluoroethyl	O
+-	O
+pentafluoropropionyl	O
+derivatives	O
+.	O
+
+In	O
+concept	O
+II	O
+62	O
+patients	O
+were	O
+treated	O
+with	O
+selective	O
+vagotomy	O
+and	O
+pyloroplasty	O
+.	O
+
+They	O
+consisted	O
+of	O
+behavioural	O
+disorders	O
+,	O
+tetraparesis	O
+,	O
+incontinence	O
+and	O
+oculomotor	O
+paralysis	O
+.	O
+
+CSF	O
+adenosine	B-GENE
+deaminase	I-GENE
+activity	O
+(	O
+ADA	O
+)	O
+was	O
+measured	O
+at	O
+the	O
+same	O
+time	O
+.	O
+
+Histamine	O
+reactivity	O
+had	O
+returned	O
+to	O
+normal	O
+in	O
+half	O
+the	O
+workers	O
+who	O
+had	O
+left	O
+their	O
+original	O
+factories	O
+,	O
+but	O
+in	O
+only	O
+one	O
+worker	O
+who	O
+had	O
+moved	O
+within	O
+her	O
+original	O
+factory	O
+.	O
+
+It	O
+was	O
+also	O
+found	O
+that	O
+there	O
+is	O
+no	O
+significant	O
+difference	O
+between	O
+the	O
+prevalence	O
+of	O
+nasal	O
+carriage	O
+of	O
+S	O
+.	O
+aureus	O
+amongst	O
+the	O
+hospital	O
+staff	O
+and	O
+the	O
+patients	O
+.	O
+
+Ficat	O
+and	O
+Bizou	O
+'	O
+s	O
+condylar	O
+depth	O
+index	O
+and	O
+the	O
+condylar	O
+-	O
+joint	O
+surface	O
+angle	O
+of	O
+Brattstrom	O
+are	O
+recommended	O
+as	O
+especially	O
+suitable	O
+methods	O
+of	O
+measurement	O
+.	O
+
+There	O
+were	O
+no	O
+significant	O
+differences	O
+in	O
+EF	O
+between	O
+the	O
+two	O
+studies	O
+,	O
+both	O
+at	O
+rest	O
+(	O
+56	O
+.	O
+0	O
++	O
+/	O
+-	O
+13	O
+.	O
+8	O
+%	O
+vs	O
+58	O
+.	O
+2	O
++	O
+/	O
+-	O
+11	O
+.	O
+7	O
+%	O
+,	O
+p	O
+=	O
+NS	O
+)	O
+and	O
+with	O
+exercise	O
+(	O
+51	O
+.	O
+1	O
++	O
+/	O
+-	O
+17	O
+.	O
+6	O
+%	O
+vs	O
+54	O
+.	O
+3	O
++	O
+/	O
+-	O
+17	O
+.	O
+6	O
+%	O
+,	O
+p	O
+=	O
+NS	O
+)	O
+and	O
+a	O
+highly	O
+significant	O
+correlation	O
+was	O
+shown	O
+between	O
+the	O
+two	O
+groups	O
+of	O
+values	O
+(	O
+rest	O
+r	O
+=	O
+0	O
+.	O
+90	O
+,	O
+exercise	O
+r	O
+=	O
+0	O
+.	O
+93	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+After	O
+MOPP	O
+therapy	O
+,	O
+complete	O
+remission	O
+of	O
+Hodgkin	O
+'	O
+s	O
+disease	O
+was	O
+accompanied	O
+by	O
+normalization	O
+of	O
+the	O
+glucocerebrosidase	B-GENE
+level	O
+and	O
+disappearance	O
+of	O
+Gaucher	O
+'	O
+s	O
+cells	O
+.	O
+
+Specifically	O
+,	O
+by	O
+the	O
+type	O
+of	O
+adjuvant	O
+therapy	O
+,	O
+the	O
+median	O
+disease	O
+-	O
+free	O
+interval	O
+and	O
+survival	O
+from	O
+stage	O
+IVA	O
+for	O
+23	O
+patients	O
+receiving	O
+Corynebacterium	O
+parvum	O
+were	O
+6	O
+.	O
+9	O
+and	O
+19	O
+months	O
+;	O
+for	O
+39	O
+patients	O
+receiving	O
+BCG	O
+,	O
+eight	O
+months	O
+and	O
+26	O
+months	O
+;	O
+for	O
+24	O
+patients	O
+receiving	O
+BCG	O
++	O
+DTIC	O
+,	O
+eight	O
+and	O
+17	O
+.	O
+4	O
+months	O
+;	O
+and	O
+for	O
+all	O
+51	O
+DTIC	O
+treated	O
+patients	O
+6	O
+.	O
+3	O
+and	O
+17	O
+.	O
+8	O
+months	O
+,	O
+respectively	O
+.	O
+
+The	O
+COP	O
+-	O
+PAWP	O
+gradient	O
+was	O
+markedly	O
+decreased	O
+in	O
+both	O
+shock	O
+and	O
+non	O
+-	O
+shock	O
+patients	O
+with	O
+pulmonary	O
+edema	O
+.	O
+
+Re	O
+:	O
+A	O
+modified	O
+method	O
+for	O
+the	O
+in	O
+vivo	O
+labeling	O
+of	O
+red	O
+blood	O
+cells	O
+with	O
+Tc	O
+-	O
+99m	O
+.	O
+
+A	O
+limited	O
+study	O
+in	O
+a	O
+glassware	O
+factory	O
+(	O
+As2O3	O
+exposure	O
+)	O
+involving	O
+the	O
+measurement	O
+of	O
+total	O
+airborne	O
+arsenic	O
+,	O
+the	O
+determination	O
+of	O
+urinary	O
+arsenic	O
+,	O
+and	O
+the	O
+evaluation	O
+of	O
+hand	O
+and	O
+mouth	O
+contamination	O
+by	O
+arsenic	O
+before	O
+and	O
+after	O
+the	O
+workshift	O
+suggests	O
+that	O
+the	O
+high	O
+urinary	O
+arsenic	O
+levels	O
+(	O
+300	O
+microgram	O
+/	O
+g	O
+creatinine	O
+)	O
+are	O
+likely	O
+to	O
+be	O
+more	O
+related	O
+to	O
+an	O
+increased	O
+oral	O
+intake	O
+from	O
+contaminated	O
+hands	O
+than	O
+to	O
+an	O
+increased	O
+absorption	O
+from	O
+the	O
+lungs	O
+.	O
+
+The	O
+pia	O
+mater	O
+at	O
+the	O
+site	O
+of	O
+the	O
+entry	O
+of	O
+blood	O
+vessels	O
+into	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Experimental	O
+reproduction	O
+of	O
+malignant	O
+catarrhal	O
+fever	O
+in	O
+Bali	O
+cattle	O
+
+1	O
+A	O
+colonic	O
+delivery	O
+system	O
+is	O
+described	O
+to	O
+deliver	O
+orally	O
+ingested	O
+drugs	O
+to	O
+the	O
+colon	O
+and	O
+release	O
+them	O
+at	O
+that	O
+site	O
+by	O
+coating	O
+with	O
+an	O
+acrylic	O
+based	O
+resin	O
+(	O
+Eudragit	O
+S	O
+)	O
+.	O
+
+Administration	O
+of	O
+the	O
+dopamine	O
+agonist	O
+bromocriptine	O
+(	O
+2	O
+.	O
+5	O
+mg	O
+three	O
+times	O
+a	O
+day	O
+for	O
+4	O
+days	O
+)	O
+suppressed	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+mean	O
+24	O
+-	O
+h	O
+plasma	O
+18	O
+-	O
+OHB	O
+levels	O
+from	O
+21	O
+.	O
+9	O
++	O
+/	O
+-	O
+2	O
+.	O
+0	O
+to	O
+14	O
+.	O
+8	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+ng	O
+/	O
+dl	O
+.	O
+
+Restarting	O
+time	O
+was	O
+not	O
+affected	O
+by	O
+magnesium	O
+cardioplegia	O
+.	O
+
+The	O
+most	O
+common	O
+types	O
+of	O
+malformations	O
+were	O
+eye	O
+defects	O
+and	O
+open	O
+coeloms	O
+.	O
+
+Repair	O
+of	O
+a	O
+cosmetic	O
+defect	O
+of	O
+the	O
+lower	O
+leg	O
+with	O
+a	O
+myocutaneous	O
+free	O
+flap	O
+.	O
+
+According	O
+to	O
+the	O
+literature	O
+,	O
+second	O
+malignant	O
+epithelial	O
+tumours	O
+are	O
+,	O
+in	O
+contrast	O
+to	O
+mesenchymal	O
+tumours	O
+such	O
+as	O
+osteosarcoma	O
+,	O
+very	O
+rare	O
+in	O
+retinoblastoma	O
+survivors	O
+.	O
+
+In	O
+Malmo	O
+,	O
+Sweden	O
+,	O
+17	O
+,	O
+181	O
+school	O
+children	O
+born	O
+in	O
+the	O
+years	O
+1961	O
+-	O
+1965	O
+were	O
+screened	O
+for	O
+scoliosis	O
+once	O
+a	O
+year	O
+between	O
+the	O
+ages	O
+of	O
+7	O
+and	O
+16	O
+years	O
+,	O
+during	O
+1971	O
+-	O
+1980	O
+.	O
+
+Intra	O
+-	O
+articular	O
+dislocation	O
+of	O
+the	O
+patella	O
+.	O
+
+This	O
+study	O
+demonstrates	O
+secretion	O
+of	O
+bicarbonate	O
+by	O
+the	O
+human	O
+stomach	O
+in	O
+vivo	O
+at	O
+a	O
+rate	O
+equivalent	O
+to	O
+10	O
+-	O
+-	O
+20	O
+%	O
+of	O
+basal	O
+acid	O
+secretion	O
+.	O
+
+Histological	O
+evaluation	O
+revealed	O
+a	O
+more	O
+than	O
+twofold	O
+increase	O
+in	O
+the	O
+number	O
+of	O
+interepithelial	O
+mononuclear	O
+cells	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+005	O
+)	O
+,	O
+while	O
+the	O
+number	O
+of	O
+epithelial	O
+cells	O
+/	O
+100	O
+microns	O
+of	O
+villous	O
+mucosa	O
+and	O
+the	O
+mean	O
+height	O
+of	O
+the	O
+epithelial	O
+cells	O
+were	O
+comparable	O
+in	O
+both	O
+groups	O
+.	O
+
+Cramps	O
+in	O
+extrapyramidal	O
+disorders	O
+.	O
+
+A	O
+suspected	O
+new	O
+storage	O
+disease	O
+in	O
+cattle	O
+.	O
+
+For	O
+various	O
+dog	O
+vessels	O
+in	O
+vivo	O
+,	O
+Q	O
+/	O
+Dk	O
+ranged	O
+from	O
+0	O
+.	O
+15	O
+to	O
+47	O
+X	O
+10	O
+(	O
+5	O
+)	O
+Torr	O
+/	O
+cm2	O
+.	O
+
+The	O
+tetraphasic	O
+action	O
+of	O
+lidocaine	O
+on	O
+CNS	O
+electrical	O
+activity	O
+and	O
+behavior	O
+in	O
+cats	O
+.	O
+
+Asymptomatic	O
+bacteriospermia	O
+and	O
+fertility	O
+
+Triumph	O
+of	O
+Leninist	O
+national	O
+policy	O
+
+The	O
+favourable	O
+effect	O
+of	O
+thymic	O
+shielding	O
+was	O
+also	O
+reflected	O
+in	O
+a	O
+significant	O
+increase	O
+of	O
+LD50	O
+/	O
+30	O
+,	O
+and	O
+the	O
+dose	O
+reduction	O
+factor	O
+was	O
+equal	O
+to	O
+2	O
+.	O
+
+The	O
+application	O
+of	O
+ultrafiltration	O
+to	O
+sample	O
+preparation	O
+in	O
+the	O
+detection	O
+and	O
+quantification	O
+of	O
+ethylene	O
+glycol	O
+in	O
+plasma	O
+by	O
+gas	O
+chromatography	O
+is	O
+described	O
+.	O
+
+Mastocytosis	O
+.	O
+
+A	O
+new	O
+Onchocerca	O
+species	O
+,	O
+a	O
+parasite	O
+of	O
+domestic	O
+cattle	O
+,	O
+in	O
+Senegal	O
+
+It	O
+was	O
+suggested	O
+that	O
+the	O
+absence	O
+of	O
+pronounced	O
+differences	O
+between	O
+conditions	O
+may	O
+have	O
+been	O
+due	O
+to	O
+the	O
+complexity	O
+of	O
+the	O
+task	O
+or	O
+the	O
+type	O
+of	O
+prompts	O
+employed	O
+.	O
+
+A	O
+limiting	O
+factor	O
+were	O
+disturbances	O
+in	O
+the	O
+system	O
+of	O
+energy	O
+transport	O
+(	O
+creatine	O
+phosphate	O
+,	O
+creatine	B-GENE
+phosphokinase	I-GENE
+)	O
+and	O
+of	O
+the	O
+calcium	O
+pump	O
+(	O
+Ca	B-GENE
++	I-GENE
++	I-GENE
+-	I-GENE
+ATPase	I-GENE
+of	O
+the	O
+sarcoplasmic	O
+reticulum	O
+,	O
+SPR	O
+)	O
+,	O
+which	O
+evidently	O
+led	O
+to	O
+a	O
+decrease	O
+of	O
+the	O
+inotropic	O
+properties	O
+of	O
+the	O
+myocardium	O
+at	O
+70	O
+%	O
+restriction	O
+of	O
+coronary	O
+blood	O
+flow	O
+.	O
+
+Serum	B-GENE
+creatine	I-GENE
+kinase	I-GENE
+(	O
+SCK	B-GENE
+)	O
+was	O
+measured	O
+in	O
+ten	O
+subjects	O
+in	O
+the	O
+laboratory	O
+before	O
+and	O
+after	O
+the	O
+performance	O
+of	O
+bicycle	O
+ergometry	O
+and	O
+a	O
+lifting	O
+task	O
+.	O
+
+Organisms	O
+were	O
+not	O
+observed	O
+in	O
+the	O
+5	O
+bobcats	O
+trapped	O
+in	O
+2	O
+other	O
+counties	O
+.	O
+
+The	O
+cause	O
+of	O
+death	O
+is	O
+often	O
+quite	O
+apparent	O
+from	O
+the	O
+pathological	O
+and	O
+toxicological	O
+findings	O
+;	O
+however	O
+,	O
+the	O
+manner	O
+of	O
+death	O
+often	O
+gives	O
+the	O
+examining	O
+official	O
+some	O
+difficulty	O
+.	O
+
+The	O
+average	O
+annual	O
+cost	O
+per	O
+head	O
+of	O
+population	O
+was	O
+US	O
++	O
+0	O
+X	O
+46	O
+.	O
+
+It	O
+is	O
+postulated	O
+that	O
+altered	O
+blood	O
+flow	O
+,	O
+mediated	O
+through	O
+the	O
+well	O
+-	O
+known	O
+prostaglandin	B-GENE
+synthetase	I-GENE
+inhibitory	O
+effects	O
+of	O
+ibuprofen	O
+,	O
+resulted	O
+in	O
+tubular	O
+necrosis	O
+.	O
+
+Either	O
+20	O
+mg	O
+mitomycin	O
+/	O
+20	O
+ml	O
+distilled	O
+water	O
+or	O
+40	O
+mg	O
+/	O
+40	O
+ml	O
+distilled	O
+water	O
+was	O
+locally	O
+instilled	O
+into	O
+the	O
+bladder	O
+with	O
+a	O
+catheter	O
+after	O
+emptying	O
+it	O
+and	O
+was	O
+left	O
+for	O
+about	O
+25	O
+-	O
+l20	O
+min	O
+.	O
+
+Both	O
+groups	O
+rejected	O
+pops	O
+with	O
+added	O
+SOA	O
+,	O
+decreasing	O
+mouthing	O
+times	O
+as	O
+SOA	O
+concentration	O
+increased	O
+.	O
+
+The	O
+mean	O
+extracted	O
+concentration	O
+of	O
+flucloxacillin	O
+obtained	O
+at	O
+operation	O
+was	O
+12	O
+.	O
+9	O
+micrograms	O
+/	O
+ml	O
+(	O
+SD	O
+5	O
+.	O
+25	O
+)	O
+in	O
+synovial	O
+fluid	O
+;	O
+2	O
+.	O
+9	O
+micrograms	O
+/	O
+g	O
+(	O
+SD	O
+3	O
+.	O
+59	O
+)	O
+in	O
+synovium	O
+;	O
+2	O
+.	O
+0	O
+micrograms	O
+/	O
+g	O
+(	O
+SD	O
+1	O
+.	O
+48	O
+)	O
+in	O
+cancellous	O
+bone	O
+and	O
+1	O
+.	O
+3	O
+micrograms	O
+/	O
+g	O
+(	O
+SD	O
+1	O
+.	O
+25	O
+)	O
+in	O
+cortical	O
+bone	O
+.	O
+
+A	O
+preliminary	O
+study	O
+of	O
+vincristine	O
+,	O
+methotrexate	O
+,	O
+and	O
+prednisolone	O
+(	O
+VM	O
+*	O
+P	O
+)	O
+combination	O
+chemotherapy	O
+for	O
+advanced	O
+adult	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphoma	O
+
+Lacrimal	O
+secretion	O
+in	O
+hyperthyroidism	O
+
+Re	O
+-	O
+examination	O
+of	O
+the	O
+ED01	O
+study	O
+.	O
+
+Based	O
+on	O
+213	O
+determinations	O
+,	O
+the	O
+control	O
+mean	O
+serum	B-GENE
+CPK	I-GENE
+activity	O
+was	O
+262	O
++	O
+/	O
+-	O
+113	O
+I	O
+.	O
+U	O
+.	O
+/	O
+liter	O
+.	O
+
+A	O
+further	O
+study	O
+on	O
+plasminogen	B-GENE
+activator	I-GENE
+release	O
+by	O
+vasoactive	O
+agents	O
+in	O
+the	O
+isolated	O
+perfused	O
+dog	O
+leg	O
+.	O
+
+CDDP	O
+is	O
+active	O
+as	O
+a	O
+single	O
+agent	O
+in	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphoma	O
+.	O
+
+Treatment	O
+of	O
+meat	O
+muscle	O
+800	O
+V	O
+for	O
+45	O
+s	O
+reduced	O
+weeping	O
+but	O
+increased	O
+slightly	O
+the	O
+rate	O
+of	O
+autoxidation	O
+of	O
+lipids	O
+.	O
+
+A	O
+method	O
+for	O
+determining	O
+cumulative	O
+behavioral	O
+toxicity	O
+after	O
+chronic	O
+oral	O
+administration	O
+of	O
+l	O
+-	O
+alpha	O
+-	O
+acetylmethadol	O
+to	O
+female	O
+rats	O
+.	O
+
+After	O
+successful	O
+subtotal	O
+parathyroidectomy	O
+,	O
+evident	O
+by	O
+the	O
+decrease	O
+of	O
+serum	O
+iPTH	B-GENE
+levels	O
+,	O
+both	O
+the	O
+CL	O
+of	O
+group	O
+2	O
+PMNs	O
+and	O
+the	O
+ability	O
+of	O
+group	O
+2	O
+sera	O
+to	O
+induce	O
+augmented	O
+CL	O
+in	O
+normal	O
+PMNs	O
+decreased	O
+(	O
+p	O
+<	O
+0	O
+.	O
+025	O
+)	O
+.	O
+
+TCZ	O
+provides	O
+quick	O
+,	O
+inexpensive	O
+,	O
+noninvasive	O
+indication	O
+of	O
+tissue	O
+necrosis	O
+,	O
+moderate	O
+-	O
+to	O
+-	O
+severe	O
+intracranial	O
+hemorrhage	O
+,	O
+and	O
+delayed	O
+brain	O
+maturation	O
+.	O
+
+The	O
+number	O
+of	O
+muricidal	O
+rats	O
+increased	O
+with	O
+increase	O
+in	O
+the	O
+duration	O
+of	O
+Cd	O
+administration	O
+in	O
+association	O
+with	O
+greater	O
+accumulation	O
+of	O
+Cd	O
+in	O
+the	O
+olfactory	O
+bulb	O
+than	O
+in	O
+any	O
+other	O
+region	O
+of	O
+the	O
+brain	O
+.	O
+
+This	O
+test	O
+should	O
+provide	O
+another	O
+practical	O
+means	O
+to	O
+study	O
+leprosy	O
+.	O
+
+The	O
+preferences	O
+were	O
+for	O
+intact	O
+vis	O
+-	O
+a	O
+-	O
+vis	O
+castrated	O
+males	O
+,	O
+though	O
+injections	O
+of	O
+TP	O
+restored	O
+the	O
+castrates	O
+'	O
+attractiveness	O
+to	O
+the	O
+females	O
+.	O
+
+Each	O
+trial	O
+consisted	O
+of	O
+light	O
+and	O
+buzzer	O
+for	O
+five	O
+seconds	O
+as	O
+conditioned	O
+stimuli	O
+and	O
+electric	O
+shock	O
+for	O
+five	O
+seconds	O
+as	O
+an	O
+unconditioned	O
+stimulus	O
+.	O
+
+Family	O
+visits	O
+and	O
+involvement	O
+in	O
+treatment	O
+of	O
+patients	O
+at	O
+a	O
+state	O
+hospital	O
+.	O
+
+A	O
+transparent	O
+overlay	O
+for	O
+assessing	O
+amplitude	O
+of	O
+ECG	O
+wave	O
+forms	O
+.	O
+
+Adverse	O
+reaction	O
+of	O
+the	O
+apparently	O
+healthy	O
+partner	O
+in	O
+response	O
+to	O
+improvement	O
+in	O
+the	O
+overtly	O
+dysfunctional	O
+partner	O
+.	O
+
+Brain	O
+scan	O
+with	O
+99mTc	O
+-	O
+labelled	O
+macroaggregated	B-GENE
+albumin	I-GENE
+(	O
+MAA	B-GENE
+brain	O
+scan	O
+)	O
+and	O
+computed	O
+tomography	O
+studies	O
+(	O
+CT	O
+)	O
+were	O
+performed	O
+on	O
+78	O
+patients	O
+with	O
+intracranial	O
+diseases	O
+.	O
+
+Inhibition	O
+of	O
+Fusarium	O
+moniliforme	O
+var	O
+.	O
+subglutinans	O
+,	O
+the	O
+causal	O
+agent	O
+of	O
+pine	O
+pitch	O
+canker	O
+,	O
+by	O
+the	O
+soil	O
+bacterium	O
+Arthrobacter	O
+sp	O
+.	O
+
+The	O
+five	O
+-	O
+drug	O
+combination	O
+of	O
+fluorouracil	O
+imidazole	O
+carboxamide	O
+dimethyl	O
+triazeno	O
+,	O
+vincristine	O
+,	O
+bis	O
+-	O
+chloroethyl	O
+nitrosourea	O
+,	O
+and	O
+prednisone	O
+(	O
+FIVB	O
++	O
+P	O
+)	O
+was	O
+given	O
+to	O
+120	O
+women	O
+with	O
+metastatic	O
+breast	O
+cancer	O
+.	O
+
+A	O
+method	O
+is	O
+described	O
+for	O
+the	O
+simultaneous	O
+determination	O
+of	O
+1	O
+,	O
+alpha	O
+-	O
+acetylmethadol	O
+(	O
+LAAM	O
+)	O
+and	O
+five	O
+active	O
+metabolites	O
+-	O
+-	O
+noracetylmethadol	O
+,	O
+dinoracetylmethadol	O
+,	O
+methadol	O
+,	O
+normethadol	O
+,	O
+and	O
+dinormethadol	O
+-	O
+-	O
+in	O
+biofluids	O
+by	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatography	O
+using	O
+a	O
+normal	O
+-	O
+phase	O
+column	O
+and	O
+a	O
+UV	O
+detector	O
+at	O
+218	O
+nm	O
+.	O
+
+Clinical	O
+and	O
+anatomical	O
+considerations	O
+
+Theory	O
+and	O
+applications	O
+of	O
+pulse	O
+dosing	O
+:	O
+a	O
+summary	O
+of	O
+the	O
+symposium	O
+.	O
+
+These	O
+results	O
+show	O
+that	O
+the	O
+neonate	O
+differs	O
+from	O
+the	O
+adult	O
+in	O
+respect	O
+of	O
+both	O
+the	O
+nature	O
+of	O
+effects	O
+of	O
+the	O
+drug	O
+and	O
+sensitivity	O
+to	O
+it	O
+.	O
+
+To	O
+evaluate	O
+the	O
+gas	O
+chromatographic	O
+electron	O
+capture	O
+detection	O
+method	O
+described	O
+earlier	O
+,	O
+23	O
+plasma	O
+samples	O
+have	O
+been	O
+analysed	O
+by	O
+both	O
+techniques	O
+.	O
+
+The	O
+hemodynamics	O
+of	O
+isoproterenol	O
+-	O
+induced	O
+cardiac	O
+failure	O
+in	O
+the	O
+rat	O
+.	O
+
+Several	O
+authors	O
+have	O
+recently	O
+reported	O
+interference	O
+in	O
+theophylline	O
+analysis	O
+by	O
+paraxanthine	O
+(	O
+1	O
+,	O
+7	O
+-	O
+dimethylxanthine	O
+)	O
+,	O
+an	O
+important	O
+metabolite	O
+of	O
+caffeine	O
+.	O
+
+Multi	O
+drug	O
+regimens	O
+like	O
+C	O
+-	O
+MOPP	O
+,	O
+CHOP	O
+and	O
+BACOP	O
+led	O
+to	O
+high	O
+remission	O
+rates	O
+and	O
+in	O
+some	O
+cases	O
+probably	O
+also	O
+to	O
+a	O
+cure	O
+of	O
+the	O
+disease	O
+.	O
+
+Morphological	O
+features	O
+of	O
+Jat	O
+dentition	O
+.	O
+
+Clinical	O
+accuracy	O
+of	O
+updated	O
+version	O
+of	O
+the	O
+Phadebas	O
+RAST	O
+test	O
+.	O
+
+Five	O
+control	O
+subjects	O
+with	O
+COPD	O
+,	O
+who	O
+performed	O
+the	O
+same	O
+sequence	O
+of	O
+tests	O
+without	O
+breathing	O
+30	O
+%	O
+O2	O
+,	O
+showed	O
+no	O
+change	O
+in	O
+flow	O
+rates	O
+or	O
+density	O
+dependence	O
+.	O
+
+Following	O
+extended	O
+recovery	O
+hippocampal	O
+EEG	O
+was	O
+normal	O
+despite	O
+extensive	O
+cellular	O
+loss	O
+in	O
+areas	O
+CA3	O
+and	O
+CA4	O
+.	O
+
+Cross	O
+reactivity	O
+in	O
+theophylline	O
+RIA	O
+kit	O
+decreased	O
+.	O
+
+Strontium	O
+-	O
+90	O
+was	O
+inject	O
+i	O
+.	O
+v	O
+.	O
+into	O
+pregnant	O
+rats	O
+on	O
+day	O
+18	O
+post	O
+conception	O
+(	O
+p	O
+.	O
+c	O
+.	O
+)	O
+.	O
+
+Recording	O
+of	O
+the	O
+digital	O
+sphygmic	O
+activity	O
+in	O
+the	O
+lower	O
+extremities	O
+with	O
+the	O
+photoplethysmographic	O
+and	O
+strain	O
+-	O
+gauge	O
+methods	O
+.	O
+
+Eight	O
+hr	O
+of	O
+acidosis	O
+caused	O
+a	O
+significant	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+decrease	O
+in	O
+P50	O
+in	O
+vitro	O
+which	O
+fell	O
+from	O
+29	O
+.	O
+0	O
+to	O
+24	O
+.	O
+4	O
+torr	O
+.	O
+
+Catheter	O
+transit	O
+slows	O
+the	O
+response	O
+to	O
+a	O
+step	O
+increase	O
+in	O
+concentration	O
+by	O
+about	O
+0	O
+.	O
+13	O
+s	O
+(	O
+from	O
+10	O
+per	O
+cent	O
+-	O
+90	O
+per	O
+cent	O
+)	O
+and	O
+prolongs	O
+the	O
+transit	O
+time	O
+through	O
+the	O
+catheter	O
+for	O
+a	O
+volatile	O
+anesthetic	O
+by	O
+about	O
+0	O
+.	O
+04	O
+s	O
+more	O
+than	O
+N2	O
+.	O
+
+These	O
+women	O
+should	O
+not	O
+be	O
+given	O
+the	O
+current	O
+estrogen	O
+PPI	O
+,	O
+which	O
+was	O
+designed	O
+to	O
+warn	O
+women	O
+of	O
+the	O
+risks	O
+of	O
+long	O
+-	O
+term	O
+estrogen	O
+use	O
+;	O
+a	O
+PPI	O
+should	O
+be	O
+written	O
+specifically	O
+for	O
+patients	O
+receiving	O
+short	O
+courses	O
+.	O
+
+The	O
+oral	O
+temperature	O
+rose	O
+and	O
+the	O
+serum	B-GENE
+creatine	I-GENE
+kinase	I-GENE
+levels	O
+fell	O
+only	O
+in	O
+those	O
+patients	O
+who	O
+were	O
+actively	O
+warmed	O
+.	O
+
+Determination	O
+of	O
+aortic	O
+distensibility	O
+and	O
+its	O
+variations	O
+in	O
+arterial	O
+hypertension	O
+.	O
+
+We	O
+studied	O
+the	O
+role	O
+of	O
+prostaglandins	O
+in	O
+acid	O
+-	O
+induced	O
+esophagitis	O
+and	O
+the	O
+associated	O
+LES	O
+hypotension	O
+by	O
+simultaneous	O
+treatment	O
+of	O
+some	O
+animals	O
+with	O
+indomethacin	O
+(	O
+150	O
+micrograms	O
+/	O
+kg	O
+intravenous	O
+)	O
+,	O
+a	O
+specific	O
+inhibitor	O
+of	O
+prostaglandin	O
+synthesis	O
+,	O
+either	O
+during	O
+production	O
+of	O
+esophagitis	O
+or	O
+during	O
+recovery	O
+.	O
+
+Since	O
+only	O
+58	O
+%	O
+of	O
+our	O
+sample	O
+could	O
+be	O
+adequately	O
+classified	O
+with	O
+one	O
+diagnosis	O
+,	O
+we	O
+expect	O
+that	O
+the	O
+ASDC	O
+nosology	O
+will	O
+need	O
+to	O
+evolve	O
+further	O
+.	O
+
+A	O
+surgical	O
+technique	O
+for	O
+correcting	O
+this	O
+problem	O
+is	O
+described	O
+.	O
+
+Effects	O
+of	O
+prostaglandin	O
+inhibitors	O
+on	O
+the	O
+onset	O
+of	O
+proteinuria	O
+and	O
+stroke	O
+in	O
+stroke	O
+-	O
+prone	O
+spontaneously	O
+hypertensive	O
+rats	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+general	O
+clinical	O
+criteria	O
+for	O
+inhalation	O
+injury	O
+-	O
+-	O
+presence	O
+of	O
+facial	O
+or	O
+oropharyngeal	O
+burns	O
+,	O
+carboxyhemoglobin	B-GENE
+levels	O
+,	O
+carbonaceous	O
+sputum	O
+,	O
+or	O
+closed	O
+space	O
+injury	O
+-	O
+-	O
+did	O
+not	O
+differentiate	O
+patients	O
+with	O
+airway	O
+injury	O
+only	O
+from	O
+those	O
+with	O
+parenchymal	O
+injury	O
+.	O
+
+Methisergide	O
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+,	O
+a	O
+blocker	O
+of	O
+serotonin	B-GENE
+receptors	I-GENE
+,	O
+prevented	O
+the	O
+development	O
+of	O
+the	O
+antinociceptive	O
+effect	O
+of	O
+serotonin	O
+.	O
+
+The	O
+plasma	O
+half	O
+-	O
+life	O
+of	O
+slow	O
+disposition	O
+phase	O
+t1	O
+/	O
+2	O
+beta	O
+,	O
+increases	O
+from	O
+0	O
+.	O
+26	O
+hour	O
+in	O
+rabbits	O
+with	O
+normal	O
+renal	O
+function	O
+to	O
+5	O
+.	O
+41	O
+hours	O
+in	O
+rabbits	O
+with	O
+severe	O
+renal	O
+impairment	O
+.	O
+
+Effects	O
+of	O
+early	O
+monocular	O
+deprivation	O
+on	O
+development	O
+of	O
+cortico	O
+-	O
+geniculate	O
+projections	O
+in	O
+the	O
+cat	O
+.	O
+
+Corticosteroid	O
+therapy	O
+is	O
+known	O
+to	O
+be	O
+hazardous	O
+in	O
+patients	O
+with	O
+occult	O
+infection	O
+but	O
+the	O
+mechanism	O
+by	O
+which	O
+the	O
+host	O
+parasite	O
+relationship	O
+is	O
+altered	O
+by	O
+steroids	O
+is	O
+not	O
+known	O
+.	O
+We	O
+have	O
+used	O
+an	O
+intestinal	O
+protozoal	O
+parasite	O
+,	O
+Giardia	O
+muris	O
+,	O
+to	O
+examine	O
+the	O
+effects	O
+of	O
+corticosteroids	O
+on	O
+the	O
+number	O
+of	O
+parasites	O
+in	O
+the	O
+intestine	O
+in	O
+the	O
+course	O
+of	O
+a	O
+primary	O
+infection	O
+.	O
+
+Static	O
+lung	O
+function	O
+in	O
+puppies	O
+after	O
+pneumonectomy	O
+.	O
+
+Bilateral	O
+Charnley	O
+arthroplasty	O
+as	O
+a	O
+single	O
+procedure	O
+.	O
+
+The	O
+relationship	O
+between	O
+estrogenic	O
+properties	O
+of	O
+Tamoxifen	O
+and	O
+breast	O
+cancer	O
+management	O
+is	O
+discussed	O
+.	O
+
+A	O
+fluoroimmunoassay	O
+for	O
+the	O
+determination	O
+of	O
+serum	O
+of	O
+plasma	O
+levels	O
+of	O
+propranolol	O
+was	O
+developed	O
+using	O
+antibodies	O
+to	O
+propranolol	O
+coupled	O
+to	O
+magnetizable	O
+solid	O
+-	O
+phase	O
+particles	O
+and	O
+fluorescein	O
+-	O
+labeled	O
+propranolol	O
+as	O
+tracer	O
+.	O
+
+The	O
+syncytial	O
+microvillous	O
+projections	O
+seemed	O
+to	O
+be	O
+more	O
+numerous	O
+and	O
+longer	O
+in	O
+CNF	O
+,	O
+otherwise	O
+the	O
+structure	O
+of	O
+the	O
+trophoblastic	O
+layer	O
+of	O
+the	O
+villi	O
+and	O
+the	O
+lining	O
+of	O
+the	O
+subtrophoblastic	O
+vessels	O
+were	O
+identical	O
+in	O
+CNF	O
+and	O
+controls	O
+.	O
+
+When	O
+pollen	O
+allergen	O
+from	O
+three	O
+grass	O
+species	O
+were	O
+used	O
+,	O
+The	O
+RAST	O
+-	O
+test	O
+results	O
+did	O
+not	O
+differ	O
+from	O
+duplicate	O
+values	O
+either	O
+.	O
+
+DMI	O
+and	O
+2	O
+-	O
+OH	O
+-	O
+DMI	O
+concentrations	O
+were	O
+determined	O
+in	O
+a	O
+similar	O
+group	O
+of	O
+61	O
+DMI	O
+-	O
+treated	O
+patients	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+in	O
+experiments	O
+in	O
+vitro	O
+that	O
+the	O
+hepatotrophic	O
+organic	O
+anions	O
+,	O
+the	O
+radiographic	O
+contrast	O
+agent	O
+(	O
+RCA	O
+)	O
+bilignost	O
+used	O
+in	O
+cholecystography	O
+and	O
+Bengal	O
+pink	O
+,	O
+have	O
+an	O
+affinity	O
+,	O
+unlike	O
+the	O
+urographic	O
+RCA	O
+triombrin	O
+and	O
+renotrophic	O
+dye	O
+indigo	O
+-	O
+carmine	O
+,	O
+for	O
+the	O
+plasmatic	O
+membranes	O
+(	O
+PM	O
+)	O
+of	O
+liver	O
+cells	O
+.	O
+
+33	O
+out	O
+of	O
+90	O
+neurons	O
+of	O
+the	O
+cat	O
+medial	O
+geniculate	O
+body	O
+revealed	O
+the	O
+selectivity	O
+of	O
+their	O
+afterdischarges	O
+to	O
+movement	O
+of	O
+sound	O
+when	O
+velocity	O
+of	O
+the	O
+movement	O
+changed	O
+from	O
+30	O
+to	O
+180	O
+deg	O
+/	O
+s	O
+.	O
+
+In	O
+controls	O
+,	O
+only	O
+modest	O
+differences	O
+were	O
+observed	O
+.	O
+
+Assay	O
+of	O
+serum	B-GENE
+immunoreactive	I-GENE
+trypsin	I-GENE
+in	O
+dried	O
+blood	O
+spots	O
+and	O
+the	O
+early	O
+detection	O
+of	O
+cystic	O
+fibrosis	O
+.	O
+
+Similar	O
+waves	O
+were	O
+seen	O
+on	O
+cross	O
+-	O
+correlating	O
+a	O
+motor	O
+unit	O
+with	O
+an	O
+electronic	O
+oscillator	O
+,	O
+confirming	O
+that	O
+their	O
+occurrence	O
+does	O
+not	O
+necessarily	O
+demonstrate	O
+the	O
+existence	O
+of	O
+active	O
+neural	O
+interactions	O
+.	O
+
+Leukocyte	O
+enzyme	O
+activity	O
+and	O
+blood	O
+lymphocyte	O
+blast	O
+transformation	O
+in	O
+chronic	O
+bronchitis	O
+
+In	O
+literature	O
+,	O
+the	O
+HBE	O
+has	O
+been	O
+displayed	O
+by	O
+application	O
+of	O
+the	O
+averaging	O
+method	O
+.	O
+
+Forty	O
+-	O
+five	O
+cases	O
+were	O
+surgically	O
+by	O
+direct	O
+approach	O
+to	O
+the	O
+tumour	O
+,	O
+while	O
+two	O
+cases	O
+were	O
+treated	O
+only	O
+with	O
+a	O
+shunt	O
+.	O
+
+In	O
+Group	O
+V	O
+,	O
+the	O
+salvaged	O
+tissue	O
+was	O
+primarily	O
+subepicardial	O
+with	O
+virtually	O
+no	O
+lateral	O
+zone	O
+of	O
+salvaged	O
+tissue	O
+(	O
+ratio	O
+of	O
+salvaged	O
+subepicardium	O
+to	O
+salvaged	O
+subendocardium	O
+14	O
+.	O
+8	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+to	O
+1	O
+)	O
+.	O
+
+Progressive	O
+100	O
+-	O
+mmHg	O
+stepwise	O
+decreases	O
+in	O
+superfusate	O
+oxygen	O
+partial	O
+pressure	O
+(	O
+PO2	O
+)	O
+from	O
+control	O
+(	O
+95	O
+%	O
+O2	O
+aeration	O
+,	O
+PO2	O
+,	O
+620	O
+-	O
+650	O
+mmHg	O
+)	O
+were	O
+produced	O
+,	O
+and	O
+subsequent	O
+changes	O
+in	O
+isometric	O
+active	O
+and	O
+resting	O
+tension	O
+were	O
+measured	O
+.	O
+
+The	O
+known	O
+B1	O
+-	O
+deficiency	O
+reaches	O
+excessive	O
+high	O
+values	O
+with	O
+light	O
+exercise	O
+.	O
+
+Based	O
+on	O
+AUC	O
+infinity	O
+analyses	O
+,	O
+the	O
+pharmacokinetics	O
+of	O
+buflomedil	O
+were	O
+found	O
+to	O
+be	O
+linear	O
+within	O
+the	O
+dose	O
+ranges	O
+studied	O
+(	O
+50	O
+to	O
+200	O
+mg	O
+for	O
+i	O
+.	O
+v	O
+.	O
+injection	O
+and	O
+150	O
+to	O
+450	O
+mg	O
+for	O
+oral	O
+administration	O
+)	O
+.	O
+
+Gastrin	B-GENE
+secretion	O
+during	O
+food	O
+stimulation	O
+in	O
+digestive	O
+system	O
+diseases	O
+
+Fibrinogen	B-GENE
+determination	O
+using	O
+the	O
+KZM	O
+-	O
+1	O
+meter	O
+
+Delayed	O
+or	O
+paradoxically	O
+emptying	O
+regions	O
+of	O
+the	O
+left	O
+ventricle	O
+were	O
+detected	O
+by	O
+a	O
+relatively	O
+new	O
+nuclear	O
+technique	O
+-	O
+-	O
+phase	O
+imaging	O
+.	O
+
+Responses	O
+to	O
+brainstem	O
+of	O
+nuclei	O
+medialis	O
+dorsalis	O
+,	O
+lateralis	O
+posterior	O
+were	O
+of	O
+considerably	O
+longer	O
+latency	O
+.	O
+
+Nineteen	O
+patients	O
+with	O
+non	O
+-	O
+visualized	O
+gallbladder	O
+with	O
+OCG	O
+subsequently	O
+had	O
+Tc	O
+-	O
+99m	O
+-	O
+PyG	O
+cholescintigraphy	O
+performed	O
+.	O
+
+One	O
+was	O
+allowed	O
+fresh	O
+drinking	O
+water	O
+ad	O
+libitum	O
+whilst	O
+the	O
+other	O
+received	O
+Aludrox	O
+in	O
+their	O
+drinking	O
+water	O
+.	O
+
+Anamnestic	O
+data	O
+were	O
+obtained	O
+from	O
+case	O
+history	O
+,	O
+smoking	O
+habits	O
+were	O
+not	O
+known	O
+in	O
+collective	O
+A	O
+and	O
+C	O
+.	O
+
+The	O
+determination	O
+of	O
+physical	O
+performance	O
+capacity	O
+was	O
+based	O
+on	O
+W170	O
+,	O
+W85	O
+%	O
+and	O
+on	O
+predicted	O
+VO2	O
+max	O
+measured	O
+with	O
+continuously	O
+increasing	O
+work	O
+load	O
+on	O
+a	O
+bicycle	O
+ergometer	O
+.	O
+
+Determination	O
+of	O
+lead	O
+in	O
+blood	O
+.	O
+
+Effect	O
+of	O
+indomethacin	O
+and	O
+prostaglandin	O
+F2	O
+alpha	O
+on	O
+parturition	O
+in	O
+swine	O
+.	O
+
+LD50	O
+values	O
+of	O
+terms	O
+of	O
+KP	O
+were	O
+84	O
+mg	O
+/	O
+kg	O
+in	O
+male	O
+rats	O
+and	O
+122	O
+mg	O
+/	O
+kg	O
+in	O
+female	O
+rats	O
+when	O
+KP	O
+-	O
+CMC	O
+was	O
+administered	O
+intrarectally	O
+,	O
+and	O
+117	O
+mg	O
+/	O
+kg	O
+in	O
+male	O
+and	O
+92	O
+mg	O
+/	O
+kg	O
+in	O
+female	O
+when	O
+KP	O
+-	O
+T10	O
+was	O
+administered	O
+intrarectally	O
+.	O
+,	O
+while	O
+peroral	O
+administration	O
+of	O
+KP	O
+-	O
+CMC	O
+showed	O
+LD50	O
+values	O
+of	O
+68	O
+mg	O
+/	O
+kg	O
+in	O
+males	O
+and	O
+78	O
+mg	O
+/	O
+kg	O
+in	O
+females	O
+in	O
+terms	O
+of	O
+KP	O
+.	O
+
+Autotransfusion	O
+was	O
+performed	O
+as	O
+follows	O
+:	O
+Heparin	O
+-	O
+ACD	O
+-	O
+B	O
+-	O
+Heparin	O
+-	O
+DPD	O
+-	O
+Heparin	O
+-	O
+ACD	O
+-	O
+B	O
+etc	O
+.	O
+
+Generally	O
+the	O
+differences	O
+between	O
+short	O
+gut	O
+and	O
+sham	O
+operation	O
+animals	O
+disappeared	O
+when	O
+the	O
+data	O
+were	O
+normalised	O
+for	O
+mucosal	O
+weight	O
+.	O
+
+A	O
+simplified	O
+thin	O
+-	O
+layer	O
+chromatographic	O
+determination	O
+of	O
+hippuric	O
+acid	O
+and	O
+methylhippuric	O
+acids	O
+.	O
+
+The	O
+architecture	O
+of	O
+microvasculature	O
+in	O
+these	O
+two	O
+regions	O
+was	O
+also	O
+examined	O
+by	O
+scanning	O
+electron	O
+microscopy	O
+,	O
+using	O
+the	O
+resin	O
+casting	O
+method	O
+.	O
+
+MSMS	O
+Council	O
+hears	O
+new	O
+public	O
+health	O
+director	O
+.	O
+
+Chordoma	O
+of	O
+the	O
+spinal	O
+cord	O
+in	O
+a	O
+F344	O
+rat	O
+.	O
+
+Micro	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatographic	O
+system	O
+with	O
+micro	O
+precolumn	O
+and	O
+dual	O
+electrochemical	O
+detector	O
+for	O
+direct	O
+injection	O
+analysis	O
+of	O
+catecholamines	O
+in	O
+body	O
+fluids	O
+.	O
+
+A	O
+narrow	O
+zone	O
+of	O
+myelin	O
+-	O
+axonal	O
+dissociation	O
+was	O
+also	O
+observed	O
+.	O
+
+The	O
+IgA	B-GENE
+deficiency	O
+is	O
+combined	O
+with	O
+the	O
+IgE	B-GENE
+one	O
+.	O
+
+In	O
+PB	O
+mice	O
+,	O
+there	O
+was	O
+only	O
+a	O
+small	O
+deficit	O
+in	O
+the	O
+number	O
+of	O
+the	O
+hippocampal	O
+pyramidal	O
+neurons	O
+compared	O
+to	O
+controls	O
+(	O
+15	O
+%	O
+,	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+no	O
+deficit	O
+in	O
+the	O
+granule	O
+cells	O
+.	O
+
+Nutritional	O
+cataracts	O
+in	O
+timber	O
+wolves	O
+.	O
+
+The	O
+quantitative	O
+determination	O
+of	O
+HBSAG	B-GENE
+-	O
+-	O
+a	O
+valuable	O
+aid	O
+in	O
+evaluating	O
+the	O
+infectiousness	O
+of	O
+hepatitis	O
+B	O
+virus	O
+carriers	O
+
+2	O
+.	O
+numerous	O
+narrow	O
+shunt	O
+vessels	O
+departing	O
+continuously	O
+from	O
+the	O
+primary	O
+arteries	O
+to	O
+feed	O
+a	O
+secondary	O
+arterial	O
+system	O
+which	O
+parallels	O
+the	O
+primary	O
+one	O
+.	O
+
+Urological	O
+complications	O
+are	O
+frequent	O
+during	O
+and	O
+after	O
+the	O
+treatment	O
+of	O
+gynecological	O
+malignancy	O
+.	O
+
+Arachnoid	O
+cyst	O
+.	O
+
+Hypotension	O
+was	O
+produced	O
+by	O
+head	O
+up	O
+tilt	O
+.	O
+
+Therefore	O
+the	O
+procedure	O
+of	O
+Lich	O
+-	O
+Gregoir	O
+is	O
+not	O
+to	O
+be	O
+recommended	O
+in	O
+adults	O
+.	O
+
+Mucoepidermoid	O
+and	O
+acinous	O
+cell	O
+carcinomas	O
+of	O
+salivary	O
+tissues	O
+.	O
+
+Twenty	O
+patients	O
+aged	O
+45	O
+or	O
+older	O
+with	O
+the	O
+diagnosis	O
+of	O
+endogenous	O
+depression	O
+were	O
+evaluated	O
+in	O
+terms	O
+of	O
+safety	O
+and	O
+efficacy	O
+in	O
+their	O
+response	O
+to	O
+multiple	O
+monitored	O
+electroconvulsive	O
+therapy	O
+(	O
+MMECT	O
+)	O
+versus	O
+single	O
+electroconvulsive	O
+therapy	O
+(	O
+SECT	O
+)	O
+.	O
+
+Longitudinal	O
+force	O
+-	O
+length	O
+relationships	O
+of	O
+guinea	O
+pig	O
+ureter	O
+were	O
+studied	O
+in	O
+vitro	O
+in	O
+animals	O
+3	O
+weeks	O
+,	O
+3	O
+months	O
+,	O
+and	O
+3	O
+years	O
+of	O
+age	O
+.	O
+
+Tests	O
+of	O
+the	O
+method	O
+indicate	O
+(	O
+1	O
+)	O
+the	O
+Mossbauer	O
+source	O
+can	O
+be	O
+placed	O
+on	O
+the	O
+basilar	O
+membrane	O
+without	O
+altering	O
+the	O
+signal	O
+-	O
+transmission	O
+properties	O
+of	O
+the	O
+cochlea	O
+,	O
+and	O
+(	O
+2	O
+)	O
+the	O
+source	O
+adheres	O
+to	O
+the	O
+basilar	O
+membrane	O
+.	O
+
+Angiographic	O
+work	O
+-	O
+up	O
+in	O
+a	O
+patient	O
+with	O
+late	O
+vaginal	O
+metastasis	O
+from	O
+a	O
+renal	O
+carcinoma	O
+.	O
+
+The	O
+authors	O
+conclude	O
+that	O
+nonspecificity	O
+of	O
+low	O
+platelet	B-GENE
+MAO	I-GENE
+as	O
+a	O
+possible	O
+correlate	O
+of	O
+bipolar	O
+affective	O
+disorder	O
+,	O
+as	O
+well	O
+as	O
+schizophrenia	O
+,	O
+increases	O
+the	O
+burden	O
+of	O
+proof	O
+necessary	O
+before	O
+findings	O
+of	O
+low	O
+platelet	B-GENE
+MAO	I-GENE
+can	O
+be	O
+accepted	O
+as	O
+primary	O
+.	O
+
+Ecthyma	O
+,	O
+a	O
+known	O
+disease	O
+,	O
+of	O
+which	O
+little	O
+is	O
+known	O
+
+Estrogen	O
+replacement	O
+,	O
+either	O
+as	O
+17	O
+beta	O
+-	O
+estradiol	O
+or	O
+beta	O
+-	O
+estradiol	O
+-	O
+3	O
+-	O
+benzoate	O
+via	O
+subcutaneous	O
+Silastic	O
+capsules	O
+,	O
+was	O
+associated	O
+with	O
+elevated	O
+rates	O
+of	O
+heat	O
+production	O
+and	O
+dry	O
+heat	O
+loss	O
+relative	O
+to	O
+untreated	O
+ovariectomized	O
+controls	O
+.	O
+
+The	O
+following	O
+aspects	O
+were	O
+assessed	O
+:	O
+(	O
+1	O
+)	O
+The	O
+effect	O
+on	O
+the	O
+cardiovascular	O
+system	O
+in	O
+terms	O
+of	O
+brachial	O
+arterial	O
+pressure	O
+,	O
+pulse	O
+rate	O
+,	O
+and	O
+oxygen	O
+consumption	O
+(	O
+VO2	O
+)	O
+during	O
+exercise	O
+in	O
+5	O
+health	O
+volunteers	O
+;	O
+(	O
+2	O
+)	O
+emg	O
+activity	O
+of	O
+the	O
+tibialis	O
+anterior	O
+and	O
+gastrocnemius	O
+muscles	O
+during	O
+exercise	O
+in	O
+the	O
+same	O
+5	O
+volunteers	O
+;	O
+and	O
+(	O
+3	O
+)	O
+postexercise	O
+ankle	O
+pressure	O
+changes	O
+in	O
+10	O
+subjects	O
+with	O
+angiographically	O
+proven	O
+occlusive	O
+arterial	O
+diseases	O
+of	O
+the	O
+lower	O
+extremities	O
+.	O
+
+It	O
+was	O
+argued	O
+that	O
+this	O
+arose	O
+from	O
+the	O
+possibility	O
+that	O
+the	O
+nature	O
+of	O
+blue	O
+collar	O
+jobs	O
+was	O
+physical	O
+,	O
+and	O
+that	O
+loss	O
+of	O
+myocardial	O
+tissue	O
+might	O
+be	O
+expected	O
+to	O
+more	O
+markedly	O
+interfere	O
+with	O
+their	O
+work	O
+efficiency	O
+(	O
+on	O
+returning	O
+to	O
+work	O
+)	O
+than	O
+it	O
+would	O
+the	O
+efficiency	O
+of	O
+the	O
+more	O
+sedentary	O
+jobs	O
+of	O
+white	O
+collar	O
+workers	O
+.	O
+
+Importance	O
+of	O
+determining	O
+the	O
+blood	O
+sulfhydryl	O
+groups	O
+in	O
+fractures	O
+of	O
+the	O
+long	O
+tubular	O
+bones	O
+complicated	O
+by	O
+infection	O
+
+The	O
+results	O
+revealed	O
+increased	O
+blood	O
+lead	O
+level	O
+associated	O
+with	O
+decreased	O
+blood	B-GENE
+haemoglobin	I-GENE
+and	O
+increased	O
+urinary	O
+excretion	O
+of	O
+delta	O
+amino	O
+levulinic	O
+acid	O
+.	O
+
+Following	O
+iv	O
+injection	O
+of	O
+0	O
+.	O
+5	O
+g	O
+galactose	O
+per	O
+kg	O
+body	O
+weight	O
+,	O
+together	O
+with	O
+2	O
+mu	O
+Ci	O
+generally	O
+14C	O
+-	O
+labelled	O
+galactose	O
+,	O
+14CO2	O
+is	O
+collected	O
+in	O
+regular	O
+intervals	O
+during	O
+one	O
+hour	O
+.	O
+
+Specific	O
+clotting	O
+factor	O
+assays	O
+showed	O
+an	O
+isolated	O
+deficiency	O
+of	O
+factor	B-GENE
+X	I-GENE
+ranging	O
+from	O
+7	O
+to	O
+12	O
+per	O
+cent	O
+on	O
+three	O
+determinations	O
+.	O
+
+Blood	O
+variables	O
+measured	O
+at	O
+eight	O
+intervals	O
+before	O
+,	O
+during	O
+,	O
+and	O
+after	O
+operation	O
+were	O
+as	O
+follows	O
+:	O
+seven	O
+plasma	O
+proteins	O
+,	O
+free	O
+hemoglobin	B-GENE
+,	O
+formed	O
+elements	O
+,	O
+and	O
+clotting	O
+functions	O
+.	O
+
+The	O
+ability	O
+of	O
+sodium	O
+phenobarbital	O
+(	O
+60	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+sodium	O
+barbital	O
+(	O
+80	O
+mg	O
+/	O
+kg	O
+)	O
+to	O
+produce	O
+a	O
+taste	O
+aversion	O
+in	O
+23	O
+hr	O
+fluid	O
+deprived	O
+rats	O
+was	O
+examined	O
+using	O
+a	O
+discrimination	O
+or	O
+two	O
+bottle	O
+taste	O
+aversion	O
+task	O
+(	O
+0	O
+.	O
+125	O
+%	O
+sodium	O
+saccharin	O
+solution	O
+or	O
+water	O
+)	O
+.	O
+
+It	O
+appears	O
+that	O
+the	O
+pulmonary	O
+gas	O
+exchange	O
+parenchyma	O
+of	O
+these	O
+smallest	O
+mammals	O
+is	O
+well	O
+suited	O
+to	O
+supply	O
+the	O
+organism	O
+with	O
+the	O
+comparatively	O
+high	O
+levels	O
+of	O
+O2	O
+required	O
+by	O
+the	O
+high	O
+metabolic	O
+rates	O
+,	O
+exhibiting	O
+a	O
+structural	O
+adaptation	O
+of	O
+the	O
+lung	O
+to	O
+higher	O
+VO2	O
+.	O
+
+Underestimations	O
+by	O
+as	O
+much	O
+as	O
+35	O
+%	O
+may	O
+occur	O
+due	O
+to	O
+the	O
+problems	O
+in	O
+the	O
+existing	O
+methodologies	O
+.	O
+
+Chemotherapy	O
+was	O
+administered	O
+without	O
+altering	O
+the	O
+course	O
+of	O
+the	O
+disorder	O
+.	O
+
+Drug	O
+inhibition	O
+of	O
+whole	O
+blood	O
+aspirin	B-GENE
+esterase	I-GENE
+.	O
+
+However	O
+,	O
+at	O
+lower	O
+temperature	O
+the	O
+positive	O
+staircase	O
+was	O
+not	O
+clear	O
+and	O
+rather	O
+negative	O
+staircase	O
+appeared	O
+(	O
+1	O
+-	O
+-	O
+3	O
+Hz	O
+)	O
+.	O
+
+Visual	O
+averaged	O
+evoked	O
+responses	O
+and	O
+platelet	B-GENE
+monoamine	I-GENE
+oxidase	I-GENE
+in	O
+patients	O
+suffering	O
+from	O
+alcoholism	O
+.	O
+
+At	O
+the	O
+end	O
+of	O
+the	O
+experiment	O
+the	O
+urinary	O
+porphyrin	O
+excretion	O
+and	O
+the	O
+porphyrin	O
+content	O
+in	O
+lijver	O
+and	O
+skin	O
+were	O
+diminished	O
+in	O
+HCB	O
+-	O
+CQ	O
+-	O
+treated	O
+animals	O
+by	O
+about	O
+50	O
+%	O
+compared	O
+to	O
+the	O
+HCB	O
+controls	O
+.	O
+
+Although	O
+stone	O
+-	O
+formers	O
+were	O
+not	O
+found	O
+to	O
+display	O
+any	O
+features	O
+of	O
+magnesium	O
+metabolism	O
+that	O
+were	O
+different	O
+from	O
+those	O
+in	O
+the	O
+control	O
+group	O
+,	O
+their	O
+lower	O
+urinary	O
+excretion	O
+of	O
+magnesium	O
+in	O
+relation	O
+to	O
+calcium	O
+may	O
+be	O
+a	O
+factor	O
+in	O
+their	O
+increased	O
+stone	O
+-	O
+forming	O
+propensity	O
+.	O
+
+A	O
+16	O
+-	O
+year	O
+follow	O
+-	O
+up	O
+study	O
+of	O
+69	O
+paraplegics	O
+with	O
+complete	O
+lesions	O
+from	O
+T1	O
+-	O
+L3	O
+is	O
+presented	O
+.	O
+
+Hippocampal	O
+stimulation	O
+overlapping	O
+conditioned	O
+stimulus	O
+preexposure	O
+produced	O
+attenuation	O
+of	O
+latent	O
+inhibition	O
+,	O
+as	O
+did	O
+stimulation	O
+presented	O
+during	O
+conditioning	O
+after	O
+preexposure	O
+.	O
+
+The	O
+centromedial	O
+amygdala	O
+and	O
+gastric	O
+pathology	O
+in	O
+rats	O
+.	O
+
+Cataract	O
+extraction	O
+in	O
+primary	O
+glaucoma	O
+
+Number	O
+and	O
+size	O
+of	O
+the	O
+myelin	O
+structures	O
+in	O
+the	O
+pneumocytes	O
+typ	O
+II	O
+increased	O
+simultaneously	O
+.	O
+
+In	O
+the	O
+intact	O
+animal	O
+,	O
+postextrasystolic	O
+potentiation	O
+depended	O
+on	O
+the	O
+basic	O
+pacing	O
+interval	O
+,	O
+t0	O
+,	O
+and	O
+the	O
+timing	O
+of	O
+the	O
+extrasystole	O
+,	O
+t1	O
+:	O
+when	O
+t0	O
+was	O
+held	O
+constant	O
+and	O
+t1	O
+was	O
+increased	O
+,	O
+potentiation	O
+decreased	O
+;	O
+when	O
+t1	O
+was	O
+held	O
+constant	O
+and	O
+t0	O
+was	O
+increased	O
+,	O
+potentiation	O
+increased	O
+.	O
+
+In	O
+spite	O
+of	O
+this	O
+and	O
+other	O
+complications	O
+of	O
+corticosteroids	O
+,	O
+she	O
+made	O
+a	O
+full	O
+recovery	O
+from	O
+the	O
+fungal	O
+infection	O
+following	O
+treatment	O
+with	O
+amphotericin	O
+B	O
+and	O
+surgical	O
+excision	O
+of	O
+the	O
+lung	O
+abscess	O
+.	O
+
+Implications	O
+of	O
+this	O
+observation	O
+for	O
+pediatrics	O
+are	O
+discussed	O
+.	O
+
+For	O
+the	O
+study	O
+of	O
+the	O
+transition	O
+of	O
+long	O
+to	O
+short	O
+waves	O
+(	O
+deep	O
+-	O
+water	O
+waves	O
+)	O
+a	O
+closed	O
+-	O
+form	O
+solution	O
+is	O
+advantageous	O
+;	O
+this	O
+can	O
+,	O
+however	O
+,	O
+only	O
+be	O
+obtained	O
+at	O
+the	O
+cost	O
+of	O
+further	O
+simplification	O
+.	O
+
+Treatment	O
+of	O
+suppurative	O
+peritonitis	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+pheochromocytoma	O
+manifesting	O
+during	O
+the	O
+third	O
+trimester	O
+of	O
+pregnancy	O
+.	O
+
+Fasting	O
+plasma	O
+and	O
+lipoprotein	O
+lipid	O
+concentrations	O
+,	O
+adipose	B-GENE
+tissue	I-GENE
+lipoprotein	I-GENE
+lipase	I-GENE
+activity	O
+,	O
+anthropometric	O
+data	O
+,	O
+alcohol	O
+consumption	O
+,	O
+smoking	O
+habits	O
+,	O
+weekly	O
+mileage	O
+run	O
+and	O
+performance	O
+on	O
+a	O
+bicycle	O
+ergometer	O
+were	O
+recorded	O
+before	O
+and	O
+after	O
+the	O
+training	O
+period	O
+.	O
+
+The	O
+C18	O
+:	O
+1	O
+:	O
+C10	O
+value	O
+is	O
+a	O
+convenient	O
+measure	O
+of	O
+these	O
+changes	O
+and	O
+can	O
+be	O
+determined	O
+more	O
+rapidly	O
+than	O
+determining	O
+all	O
+the	O
+lower	O
+fatty	O
+acids	O
+.	O
+
+A	O
+progressive	O
+growth	O
+of	O
+blood	O
+erythrocyte	O
+membrane	O
+injury	O
+has	O
+been	O
+demonstrated	O
+after	O
+rats	O
+were	O
+exposed	O
+to	O
+gamma	O
+-	O
+irradiaton	O
+at	O
+a	O
+dose	O
+of	O
+100	O
+to	O
+500	O
+Gy	O
+.	O
+
+Within	O
+the	O
+3	O
+'	O
+terminal	O
+50	O
+nucleotides	O
+,	O
+the	O
+mouse	B-GENE
+mt	I-GENE
+12S	I-GENE
+rRNA	I-GENE
+contains	O
+a	O
+potential	O
+10	O
+bp	O
+hairpin	O
+structure	O
+and	O
+a	O
+sequence	O
+of	O
+15	O
+consecutive	O
+nucleotides	O
+common	O
+to	O
+the	O
+RNA	O
+of	O
+the	O
+small	O
+ribosomal	O
+subunit	O
+in	O
+all	O
+systems	O
+,	O
+but	O
+does	O
+not	O
+contain	O
+the	O
+mRNA	O
+binding	O
+site	O
+(	O
+ACCUCC	O
+)	O
+found	O
+in	O
+E	O
+.	O
+coli	O
+and	O
+corn	O
+chloroplast	O
+rRNAs	O
+.	O
+
+Thirty	O
+cadaver	O
+brains	O
+were	O
+examined	O
+under	O
+X	O
+6	O
+to	O
+16	O
+magnification	O
+in	O
+order	O
+to	O
+define	O
+the	O
+microsurgical	O
+anatomy	O
+of	O
+the	O
+pineal	O
+region	O
+,	O
+particularly	O
+the	O
+relationship	O
+of	O
+the	O
+pineal	O
+body	O
+,	O
+posterior	O
+cerebral	O
+artery	O
+,	O
+superior	O
+cerebellar	O
+artery	O
+,	O
+vein	O
+of	O
+Galen	O
+,	O
+basal	O
+vein	O
+of	O
+Rosenthal	O
+,	O
+internal	O
+cerebral	O
+vein	O
+,	O
+straight	O
+sinus	O
+,	O
+bridging	O
+vein	O
+,	O
+the	O
+size	O
+of	O
+the	O
+tentorial	O
+notch	O
+,	O
+and	O
+the	O
+third	O
+and	O
+the	O
+fourth	O
+cranial	O
+nerves	O
+.	O
+
+Serum	O
+antibody	O
+titre	O
+was	O
+not	O
+significantly	O
+associated	O
+with	O
+the	O
+recurrence	O
+rate	O
+or	O
+the	O
+duration	O
+of	O
+infection	O
+.	O
+
+We	O
+propose	O
+that	O
+refeeding	O
+may	O
+be	O
+an	O
+important	O
+mechanism	O
+for	O
+activation	O
+of	O
+certain	O
+viral	O
+infections	O
+previously	O
+suppressed	O
+by	O
+famine	O
+.	O
+
+One	O
+hundred	O
+twenty	O
+units	O
+of	O
+deglycerolized	O
+red	O
+blood	O
+cells	O
+,	O
+some	O
+with	O
+glycerol	O
+added	O
+so	O
+as	O
+to	O
+exceed	O
+an	O
+acceptable	O
+1	O
+%	O
+glycerol	O
+content	O
+,	O
+had	O
+measurements	O
+made	O
+of	O
+the	O
+post	O
+-	O
+wash	O
+supernatant	O
+fluid	O
+by	O
+refractive	O
+index	O
+and	O
+osmometry	O
+.	O
+
+The	O
+symptoms	O
+and	O
+objective	O
+findings	O
+were	O
+caused	O
+by	O
+a	O
+malignant	O
+lymphoma	O
+,	O
+and	O
+the	O
+diagnosis	O
+was	O
+established	O
+from	O
+a	O
+drill	O
+biopsy	O
+.	O
+
+Our	O
+study	O
+differs	O
+from	O
+previous	O
+studies	O
+in	O
+that	O
+it	O
+is	O
+limited	O
+to	O
+one	O
+diagnostic	O
+entity	O
+,	O
+yet	O
+at	O
+the	O
+same	O
+time	O
+evaluates	O
+a	O
+broad	O
+range	O
+of	O
+social	O
+and	O
+work	O
+-	O
+related	O
+factors	O
+in	O
+disability	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+a	O
+raised	O
+hydroxykynurenine	O
+/	O
+hydroxyanthranilic	O
+acid	O
+ratio	O
+does	O
+not	O
+necessarily	O
+indicate	O
+vitamin	O
+B6	O
+deficiency	O
+but	O
+may	O
+represent	O
+a	O
+nonspecific	O
+response	O
+of	O
+tryptophan	O
+metabolism	O
+to	O
+stress	O
+.	O
+
+All	O
+control	O
+persons	O
+had	O
+a	O
+normal	O
+reaction	O
+to	O
+DNFB	O
+.	O
+
+In	O
+a	O
+control	O
+group	O
+both	O
+common	O
+carotid	O
+arteries	O
+(	O
+CCA	O
+)	O
+were	O
+ligated	O
+.	O
+
+At	O
+pH	O
+6	O
+.	O
+9	O
+,	O
+the	O
+same	O
+lidocaine	O
+concentrations	O
+significantly	O
+reduced	O
+resting	O
+potential	O
+(	O
+3	O
+-	O
+10	O
+%	O
+)	O
+,	O
+action	O
+potential	O
+amplitude	O
+(	O
+3	O
+-	O
+8	O
+%	O
+)	O
+and	O
+Vmax	O
+(	O
+14	O
+-	O
+22	O
+%	O
+)	O
+.	O
+
+Simultaneous	O
+right	O
+and	O
+left	O
+adrenal	O
+and	O
+peripheral	O
+blood	O
+samples	O
+were	O
+collected	O
+for	O
+determination	O
+of	O
+oestrone	O
+(	O
+E1	O
+)	O
+and	O
+oestradiol	O
+(	O
+E2	O
+)	O
+.	O
+
+Arm	O
+function	O
+tests	O
+.	O
+
+All	O
+lambs	O
+with	O
+B	O
+breeding	O
+had	O
+significantly	O
+higher	O
+Hb	B-GENE
+levels	O
+at	O
+the	O
+end	O
+of	O
+the	O
+experiment	O
+than	O
+did	O
+NB	O
+lambs	O
+.	O
+b	O
+and	O
+S	O
+x	O
+B	O
+lambs	O
+had	O
+higher	O
+(	O
+P	O
+<	O
+.	O
+05	O
+)	O
+Hb	B-GENE
+levels	O
+than	O
+the	O
+D	O
+x	O
+B	O
+lambs	O
+,	O
+and	O
+B	O
+lambs	O
+had	O
+the	O
+highest	O
+(	O
+P	O
+<	O
+.	O
+05	O
+)	O
+mean	O
+corpuscular	O
+hemoglobin	B-GENE
+concentrations	O
+.	O
+
+The	O
+same	O
+response	O
+occurs	O
+whether	O
+acrylamide	O
+is	O
+given	O
+immediately	O
+after	O
+nerve	O
+ligation	O
+or	O
+1	O
+week	O
+later	O
+.	O
+
+The	O
+operation	O
+recommended	O
+is	O
+excision	O
+of	O
+3	O
+mm	O
+of	O
+central	O
+slip	O
+followed	O
+by	O
+end	O
+-	O
+to	O
+-	O
+end	O
+repair	O
+of	O
+the	O
+tendon	O
+.	O
+
+In	O
+the	O
+unclipped	O
+group	O
+arterial	O
+pressure	O
+decreased	O
+50	O
+mmHg	O
+to	O
+normal	O
+by	O
+24	O
+h	O
+and	O
+was	O
+associated	O
+with	O
+increased	O
+diuresis	O
+and	O
+a	O
+small	O
+decrease	O
+in	O
+blood	O
+volume	O
+(	O
+9	O
+.	O
+8	O
+%	O
+)	O
+.	O
+
+Marked	O
+sedative	O
+activity	O
+was	O
+observed	O
+with	O
+9	O
+-	O
+methoxy	O
+-	O
+5	O
+-	O
+phenylpyrrolo	O
+[	O
+2	O
+,	O
+1	O
+-	O
+d	O
+]	O
+[	O
+1	O
+,	O
+5	O
+]	O
+benzothiazepin	O
+-	O
+6	O
+,	O
+6	O
+-	O
+dioxide	O
+(	O
+NF19	O
+)	O
+and	O
+9	O
+-	O
+chloro	O
+-	O
+5	O
+-	O
+p	O
+-	O
+nitrophenylpyrrolo	O
+[	O
+2	O
+,	O
+1	O
+-	O
+d	O
+]	O
+[	O
+1	O
+,	O
+5	O
+]	O
+benzothiazepin	O
+-	O
+6	O
+,	O
+6	O
+-	O
+dioxide	O
+(	O
+NF20	O
+)	O
+.	O
+
+In	O
+patients	O
+,	O
+the	O
+effect	O
+of	O
+CCK	B-GENE
+-	O
+PZ	B-GENE
+on	O
+the	O
+movement	O
+of	O
+the	O
+terminal	O
+part	O
+of	O
+the	O
+bile	O
+duct	O
+was	O
+measured	O
+with	O
+a	O
+pressure	O
+sensor	O
+using	O
+a	O
+duodenofiberscope	O
+.	O
+
+As	O
+high	O
+-	O
+speed	O
+,	O
+volumetric	O
+imaging	O
+,	O
+computed	O
+tomographic	O
+scan	O
+machines	O
+such	O
+as	O
+the	O
+Dynamic	O
+Spatial	O
+Reconstructor	O
+become	O
+available	O
+with	O
+higher	O
+density	O
+resolution	O
+,	O
+perhaps	O
+a	O
+single	O
+injection	O
+of	O
+contrast	O
+agent	O
+into	O
+the	O
+right	O
+atrium	O
+or	O
+even	O
+a	O
+peripheral	O
+vein	O
+may	O
+be	O
+adequate	O
+to	O
+obtain	O
+all	O
+these	O
+measurements	O
+.	O
+
+The	O
+ESEG	O
+'	O
+s	O
+are	O
+a	O
+direct	O
+result	O
+of	O
+the	O
+NEXT	O
+study	O
+.	O
+
+The	O
+potentially	O
+SLE	O
+-	O
+inducing	O
+drugs	O
+are	O
+reviewed	O
+.	O
+
+A	O
+third	O
+series	O
+of	O
+mice	O
+were	O
+given	O
+a	O
+single	O
+injection	O
+of	O
+5	O
+-	O
+OH	O
+-	O
+DA	O
+,	O
+sacrificed	O
+,	O
+and	O
+prepared	O
+for	O
+ultrastructural	O
+study	O
+.	O
+
+Fourteen	O
+different	O
+species	O
+(	O
+eight	O
+Platyhelmintha	O
+,	O
+one	O
+Nematoda	O
+and	O
+five	O
+Crustacea	O
+)	O
+have	O
+been	O
+inventorized	O
+.	O
+
+No	O
+symptoms	O
+other	O
+than	O
+hot	O
+flush	O
+showed	O
+such	O
+significant	O
+correlation	O
+with	O
+plasma	O
+epinephrine	O
+or	O
+norepinephrine	O
+levels	O
+.	O
+
+The	O
+mean	O
+values	O
+of	O
+the	O
+concentrations	O
+of	O
+the	O
+components	O
+due	O
+to	O
+tobacco	O
+smoke	O
+are	O
+:	O
+CO	O
+=	O
+1	O
+.	O
+1	O
+ppm	O
+,	O
+NO	O
+=	O
+32	O
+ppb	O
+,	O
+NO2	O
+=	O
+24	O
+ppb	O
+,	O
+nicotine	O
+=	O
+0	O
+.	O
+9	O
+micrograms	O
+/	O
+m3	O
+,	O
+particulate	O
+matter	O
+=	O
+133	O
+micrograms	O
+/	O
+m3	O
+.	O
+
+The	O
+average	O
+backscatter	O
+coefficient	O
+was	O
+six	O
+time	O
+larger	O
+in	O
+regions	O
+of	O
+infarct	O
+studied	O
+8	O
+-	O
+-	O
+10	O
+weeks	O
+after	O
+occlusion	O
+than	O
+that	O
+in	O
+regions	O
+of	O
+infarct	O
+studied	O
+5	O
+-	O
+-	O
+6	O
+weeks	O
+after	O
+occlusion	O
+.	O
+
+At	O
+4	O
+wk	O
+however	O
+,	O
+tumor	O
+relapse	O
+was	O
+noted	O
+in	O
+6	O
+of	O
+7	O
+group	O
+4	O
+responders	O
+,	O
+10	O
+of	O
+12	O
+in	O
+group	O
+5	O
+,	O
+13	O
+of	O
+16	O
+in	O
+group	O
+7	O
+,	O
+but	O
+only	O
+4	O
+of	O
+19	O
+group	O
+8	O
+responders	O
+(	O
+p	O
+less	O
+than	O
+.	O
+001	O
+group	O
+8	O
+versus	O
+4	O
+,	O
+5	O
+,	O
+7	O
+)	O
+.	O
+
+Early	O
+infection	O
+was	O
+detected	O
+in	O
+one	O
+of	O
+50	O
+control	O
+women	O
+who	O
+gave	O
+birth	O
+to	O
+a	O
+healthy	O
+infant	O
+.	O
+
+Pentachlorophenol	O
+accelerates	O
+the	O
+onset	O
+of	O
+HCB	O
+porphyria	O
+,	O
+in	O
+other	O
+words	O
+it	O
+increases	O
+the	O
+total	O
+urinary	O
+porphyrin	O
+excretion	O
+and	O
+causes	O
+an	O
+earlier	O
+disturbance	O
+of	O
+the	O
+porphyrin	O
+pattern	O
+.	O
+
+Family	O
+planning	O
+continues	O
+to	O
+play	O
+a	O
+minor	O
+role	O
+,	O
+and	O
+only	O
+25	O
+.	O
+3	O
+per	O
+cent	O
+of	O
+all	O
+patients	O
+reviewed	O
+took	O
+to	O
+oral	O
+contraceptives	O
+for	O
+shorter	O
+or	O
+longer	O
+periods	O
+of	O
+time	O
+.	O
+-	O
+The	O
+percentages	O
+of	O
+primiparae	O
+and	O
+secundiparae	O
+in	O
+all	O
+births	O
+as	O
+well	O
+as	O
+the	O
+high	O
+percentage	O
+of	O
+multigravidity	O
+are	O
+parameters	O
+by	O
+which	O
+the	O
+approach	O
+to	O
+reproduction	O
+differs	O
+substantively	O
+from	O
+behaviour	O
+patterns	O
+in	O
+Europe	O
+.	O
+
+The	O
+term	O
+osteomesopycnosis	O
+is	O
+proposed	O
+for	O
+a	O
+sclerosing	O
+bone	O
+disease	O
+with	O
+dominant	O
+inheritance	O
+that	O
+has	O
+been	O
+discovered	O
+in	O
+five	O
+members	O
+of	O
+four	O
+different	O
+families	O
+.	O
+
+The	O
+87K	O
+protein	O
+,	O
+together	O
+with	O
+proteins	O
+of	O
+105	O
+,	O
+000	O
+and	O
+75	O
+,	O
+000	O
+daltons	O
+,	O
+are	O
+translated	O
+from	O
+leftward	O
+transcribed	O
+(	O
+1	O
+-	O
+strand	O
+)	O
+messenger	O
+RNAs	O
+that	O
+are	O
+complementary	O
+to	O
+the	O
+viral	O
+genome	O
+between	O
+positions	O
+11	O
+.	O
+2	O
+and	O
+31	O
+.	O
+5	O
+.	O
+
+The	O
+identification	O
+of	O
+viable	O
+myocardium	O
+with	O
+both	O
+99mTc	O
+-	O
+tetrofosmin	O
+and	O
+201Tl	O
+can	O
+be	O
+greatly	O
+enhanced	O
+to	O
+a	O
+similar	O
+degree	O
+if	O
+the	O
+severity	O
+of	O
+reduction	O
+in	O
+activity	O
+within	O
+nonreversible	O
+defects	O
+is	O
+considered	O
+.	O
+
+The	O
+temporal	O
+component	O
+lacked	O
+a	O
+mandibular	O
+fossa	O
+as	O
+well	O
+as	O
+articular	O
+eminence	O
+.	O
+
+EUK	O
+-	O
+8	O
+is	O
+a	O
+novel	O
+,	O
+synthetic	O
+,	O
+low	O
+-	O
+molecular	O
+-	O
+weight	O
+salen	O
+-	O
+manganese	O
+complex	O
+that	O
+exhibits	O
+both	O
+superoxide	B-GENE
+dismutase	I-GENE
+and	O
+catalase	B-GENE
+activities	O
+in	O
+vitro	O
+.	O
+
+The	O
+protein	B-GENE
+ELT	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+encoded	O
+by	O
+a	O
+single	O
+-	O
+copy	O
+gene	O
+homologous	O
+to	O
+the	O
+GATA	B-GENE
+family	I-GENE
+of	I-GENE
+vertebrate	I-GENE
+transcription	I-GENE
+factors	I-GENE
+,	O
+is	O
+potentially	O
+capable	O
+of	O
+interacting	O
+with	O
+this	O
+element	O
+.	O
+
+However	O
+,	O
+in	O
+contrast	O
+with	O
+previous	O
+in	O
+vitro	O
+cell	O
+-	O
+free	O
+integration	O
+studies	O
+,	O
+alteration	O
+of	O
+the	O
+highly	O
+conserved	O
+CA	O
+dinucleotide	O
+resulted	O
+in	O
+a	O
+mutant	O
+which	O
+still	O
+retained	O
+40	O
+%	O
+of	O
+wild	O
+-	O
+type	O
+integration	O
+activity	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+although	O
+PI2	O
+and	O
+PI3	O
+viruses	O
+belong	O
+to	O
+the	O
+same	O
+parainfluenza	O
+virus	O
+genus	O
+,	O
+these	O
+viruses	O
+show	O
+marked	O
+differences	O
+with	O
+respect	O
+to	O
+functional	O
+requirements	O
+for	O
+the	O
+cytoplasmic	O
+tail	O
+of	O
+the	O
+F	B-GENE
+glycoprotein	I-GENE
+.	O
+
+By	O
+site	O
+-	O
+specific	O
+mutagenesis	O
+,	O
+we	O
+also	O
+show	O
+that	O
+individual	O
+ICP27	B-GENE
+C	I-GENE
+-	I-GENE
+terminal	I-GENE
+amino	I-GENE
+acid	I-GENE
+residues	I-GENE
+that	O
+are	O
+positionally	O
+conserved	O
+in	O
+ICP27	B-GENE
+homologs	I-GENE
+in	O
+other	O
+herpesviruses	O
+(	O
+D	O
+-	O
+357	O
+,	O
+E	O
+-	O
+358	O
+,	O
+H	O
+-	O
+479	O
+,	O
+C	O
+-	O
+400	O
+,	O
+C	O
+-	O
+483	O
+,	O
+and	O
+C	O
+-	O
+488	O
+)	O
+are	O
+critical	O
+for	O
+trans	O
+-	O
+regulatory	O
+activity	O
+.	O
+
+Magnetic	O
+resonance	O
+imaging	O
+(	O
+MRI	O
+)	O
+has	O
+enabled	O
+us	O
+to	O
+see	O
+the	O
+spinal	O
+intramedullary	O
+pathology	O
+as	O
+differences	O
+in	O
+signal	O
+intensity	O
+.	O
+
+Patients	O
+with	O
+psychotropic	O
+drugs	O
+showed	O
+significantly	O
+higher	O
+PRL	B-GENE
+levels	O
+.	O
+
+The	O
+Laser	O
+Scanning	O
+Ophthalmoscope	O
+enables	O
+a	O
+fundus	O
+-	O
+based	O
+examination	O
+and	O
+therefore	O
+allows	O
+exact	O
+comparison	O
+between	O
+morphologic	O
+appearance	O
+and	O
+corresponding	O
+function	O
+.	O
+
+Malaria	O
+,	O
+anaemia	O
+,	O
+and	O
+HIV	O
+-	O
+1	O
+transmission	O
+in	O
+central	O
+Africa	O
+.	O
+
+In	O
+addition	O
+,	O
+two	O
+-	O
+dimensional	O
+nuclear	O
+magnetic	O
+resonance	O
+studies	O
+with	O
+F17A	O
+,	O
+K13Q	O
+,	O
+F15Y	O
+and	O
+F27Y	O
+revealed	O
+that	O
+the	O
+mutants	O
+have	O
+the	O
+same	O
+overall	O
+structure	O
+as	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+CspB	I-GENE
+protein	I-GENE
+.	O
+
+Considerably	O
+high	O
+levels	O
+of	O
+IgE	B-GENE
+antibodies	I-GENE
+was	O
+also	O
+established	O
+while	O
+other	O
+pollens	O
+did	O
+not	O
+show	O
+such	O
+correspondence	O
+.	O
+
+This	O
+is	O
+particularly	O
+intriguing	O
+because	O
+SKUT	O
+-	O
+1B	O
+-	O
+20	O
+cells	O
+lack	O
+the	O
+transcription	O
+factor	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Some	O
+strains	O
+of	O
+A	O
+.	O
+parasiticus	O
+produced	O
+all	O
+four	O
+aflatoxins	O
+B1	O
+B2	O
+G1	O
+G2	O
+,	O
+while	O
+the	O
+other	O
+ones	O
+produced	O
+AF	O
+B1	O
++	O
+G1	O
+only	O
+,	O
+with	O
+concentrations	O
+of	O
+aflatoxins	O
+from	O
+0	O
+.	O
+1	O
+to	O
+450	O
+mg	O
+/	O
+kg	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+new	O
+,	O
+larger	O
+rat	B-GENE
+B	I-GENE
+-	I-GENE
+myc	I-GENE
+genomic	I-GENE
+clone	I-GENE
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+nine	O
+and	O
+51	O
+terminal	O
+amino	O
+acid	O
+forms	O
+already	O
+known	O
+,	O
+we	O
+identified	O
+a	O
+third	O
+with	O
+43	O
+terminal	O
+amino	O
+acids	O
+predicted	O
+to	O
+encode	O
+a	O
+novel	O
+RET	B-GENE
+protein	I-GENE
+isoform	I-GENE
+.	O
+
+Both	O
+classes	O
+of	O
+MHBst	B-GENE
+proteins	I-GENE
+were	O
+found	O
+to	O
+form	O
+dimers	O
+;	O
+an	O
+which	O
+is	O
+involved	O
+in	O
+mediating	O
+the	O
+dimerization	O
+.	O
+
+She	O
+had	O
+been	O
+receiving	O
+MTX	O
+7	O
+.	O
+5	O
+mg	O
+/	O
+week	O
+for	O
+2	O
+.	O
+5	O
+months	O
+because	O
+of	O
+her	O
+vasculitis	O
+symptoms	O
+.	O
+
+Analysis	O
+of	O
+the	O
+sequence	O
+identified	O
+four	O
+open	O
+reading	O
+frames	O
+(	O
+ORFs	O
+)	O
+which	O
+are	O
+designated	O
+UL1	B-GENE
+,	O
+UL2	B-GENE
+,	O
+UL3	B-GENE
+,	O
+and	O
+UL3	B-GENE
+.	I-GENE
+5	I-GENE
+based	O
+on	O
+their	O
+homology	O
+with	O
+proteins	O
+of	O
+herpes	O
+simplex	O
+virus	O
+-	O
+1	O
+(	O
+HSV	O
+-	O
+1	O
+)	O
+,	O
+pseudorabies	O
+virus	O
+(	O
+PRV	O
+)	O
+,	O
+equine	O
+herpesvirus	O
+-	O
+1	O
+,	O
+and	O
+varicella	O
+-	O
+zoster	O
+virus	O
+.	O
+
+These	O
+HPV16	O
+E6	B-GENE
+/	O
+E7	B-GENE
+cDNAs	O
+were	O
+cloned	O
+under	O
+the	O
+SV40	B-GENE
+enhancer	I-GENE
+/	I-GENE
+promoter	I-GENE
+and	O
+the	O
+MMTV	B-GENE
+LTR	I-GENE
+to	O
+examine	O
+the	O
+activities	O
+of	O
+ras	B-GENE
+-	O
+collaborative	O
+transformation	O
+and	O
+induction	O
+of	O
+cellular	O
+DNA	O
+synthesis	O
+,	O
+both	O
+of	O
+which	O
+depend	O
+on	O
+the	O
+E7	B-GENE
+gene	I-GENE
+product	O
+.	O
+
+Correlation	O
+coefficients	O
+between	O
+the	O
+reference	O
+methods	O
+and	O
+NIT	O
+were	O
+>	O
+or	O
+=	O
+0	O
+.	O
+95	O
+for	O
+water	O
+,	O
+fat	O
+,	O
+crude	O
+protein	O
+and	O
+connective	O
+-	O
+tissue	O
+-	O
+protein	O
+frei	O
+meat	O
+protein	O
+,	O
+and	O
+>	O
+or	O
+=	O
+0	O
+.	O
+86	O
+for	O
+connective	O
+-	O
+tissue	O
+-	O
+protein	O
+.	O
+
+The	O
+translation	O
+products	O
+of	O
+both	O
+clones	O
+are	O
+highly	O
+homologous	O
+to	O
+APS1	B-GENE
+(	O
+66	O
+and	O
+86	O
+%	O
+identity	O
+,	O
+respectively	O
+)	O
+over	O
+their	O
+entire	O
+lengths	O
+,	O
+including	O
+amino	O
+terminal	O
+sequences	O
+resembling	O
+transit	O
+peptides	O
+for	O
+plastid	O
+localization	O
+.	O
+
+The	O
+serum	O
+levels	O
+of	O
+IgE	B-GENE
+,	O
+and	O
+asIgE	B-GENE
+and	O
+IgG	B-GENE
+-	I-GENE
+4	I-GENE
+against	O
+14	O
+common	O
+food	O
+allergens	O
+were	O
+determined	O
+.	O
+
+Two	O
+experiments	O
+investigating	O
+the	O
+effects	O
+of	O
+short	O
+-	O
+term	O
+spaceflight	O
+on	O
+cancellous	O
+bone	O
+turnover	O
+were	O
+carried	O
+out	O
+:	O
+Physiological	O
+Systems	O
+Experiment	O
+-	O
+1	O
+(	O
+PSE	O
+-	O
+1	O
+)	O
+(	O
+a	O
+4	O
+-	O
+d	O
+orbital	O
+spaceflight	O
+)	O
+and	O
+PSE	O
+-	O
+2	O
+(	O
+a	O
+10	O
+-	O
+d	O
+flight	O
+)	O
+.	O
+
+Functional	O
+analysis	O
+of	O
+aryl	B-GENE
+hydrocarbon	I-GENE
+receptor	I-GENE
+nuclear	I-GENE
+translocator	I-GENE
+interactions	O
+with	O
+aryl	B-GENE
+hydrocarbon	I-GENE
+receptor	I-GENE
+in	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+.	O
+
+Histopathologic	O
+observations	O
+showed	O
+that	O
+both	O
+somatostatin	B-GENE
+and	O
+triamcinolone	O
+acetonide	O
+reduced	O
+the	O
+inflammatory	O
+signs	O
+in	O
+the	O
+joint	O
+structures	O
+,	O
+although	O
+triamcinolone	O
+acetonide	O
+appeared	O
+to	O
+be	O
+more	O
+effective	O
+.	O
+
+An	O
+approach	O
+to	O
+a	O
+biomathematical	O
+model	O
+of	O
+lymphocytopoiesis	O
+.	O
+
+The	O
+influenza	O
+virus	O
+NS1	B-GENE
+protein	O
+is	O
+a	O
+unique	O
+posttranscriptional	O
+regulator	O
+that	O
+has	O
+two	O
+activities	O
+:	O
+inhibition	O
+of	O
+the	O
+nuclear	O
+export	O
+of	O
+poly	O
+A	O
+-	O
+containing	O
+mRNAs	O
+and	O
+inhibition	O
+of	O
+pre	O
+-	O
+mRNA	O
+splicing	O
+.	O
+
+These	O
+are	O
+two	O
+regions	O
+of	O
+known	O
+conserved	O
+synteny	O
+,	O
+providing	O
+further	O
+evidence	O
+that	O
+the	O
+human	B-GENE
+STEP	I-GENE
+is	O
+a	O
+true	O
+homolog	O
+of	O
+the	O
+murine	B-GENE
+STEP	I-GENE
+gene	I-GENE
+.	O
+
+Molecular	O
+cloning	O
+of	O
+the	O
+human	O
+homolog	O
+of	O
+a	O
+striatum	B-GENE
+-	I-GENE
+enriched	I-GENE
+phosphatase	I-GENE
+(	B-GENE
+STEP	I-GENE
+)	I-GENE
+gene	I-GENE
+and	O
+chromosomal	O
+mapping	O
+of	O
+the	O
+human	O
+and	O
+murine	O
+loci	O
+.	O
+
+Carbonic	B-GENE
+anhydrase	I-GENE
+V	I-GENE
+(	O
+CA	B-GENE
+V	I-GENE
+)	O
+is	O
+expressed	O
+in	O
+mitochondrial	O
+matrix	O
+in	O
+liver	O
+and	O
+several	O
+other	O
+tissues	O
+.	O
+
+Vitamin	O
+D3	O
+plus	O
+nicotine	O
+treatment	O
+produced	O
+parallel	O
+increases	O
+in	O
+cardiac	O
+mass	O
+and	O
+elastic	O
+modulus	O
+,	O
+with	O
+a	O
+significant	O
+correlation	O
+between	O
+the	O
+two	O
+.	O
+
+The	O
+latter	O
+domain	O
+appears	O
+to	O
+be	O
+involved	O
+in	O
+targeting	O
+Num1p	B-GENE
+to	O
+the	O
+mother	O
+cell	O
+cortex	O
+.	O
+
+This	O
+finding	O
+is	O
+consistent	O
+with	O
+the	O
+notion	O
+that	O
+the	O
+dsRNA	O
+binding	O
+domains	O
+may	O
+be	O
+composed	O
+of	O
+two	O
+separate	O
+functional	O
+subdomains	O
+.	O
+
+Preferential	O
+heterodimeric	O
+parallel	O
+coiled	O
+-	O
+coil	O
+formation	O
+by	O
+synthetic	B-GENE
+Max	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+leucine	I-GENE
+zippers	I-GENE
+:	O
+a	O
+description	O
+of	O
+putative	O
+electrostatic	O
+interactions	O
+responsible	O
+for	O
+the	O
+specificity	O
+of	O
+heterodimerization	O
+.	O
+
+Comparison	O
+to	O
+other	O
+coxI	B-GENE
+genes	I-GENE
+revealed	O
+a	O
+966	O
+-	O
+bp	O
+group	O
+I	O
+intron	O
+,	O
+which	O
+,	O
+based	O
+on	O
+homology	O
+with	O
+the	O
+related	O
+yeast	B-GENE
+coxI	I-GENE
+intron	I-GENE
+aI4	I-GENE
+,	O
+potentially	O
+encodes	O
+a	O
+279	O
+-	O
+amino	O
+-	O
+acid	O
+site	O
+-	O
+specific	O
+DNA	B-GENE
+endonuclease	I-GENE
+.	O
+
+We	O
+studied	O
+the	O
+GR	B-GENE
+in	O
+DMS	O
+-	O
+79	O
+cells	O
+derived	O
+from	O
+a	O
+human	O
+ACTH	B-GENE
+-	O
+secreting	O
+small	O
+cell	O
+lung	O
+cancer	O
+.	O
+
+This	O
+study	O
+analyzed	O
+whether	O
+the	O
+localization	O
+of	O
+an	O
+accessory	O
+pathway	O
+could	O
+be	O
+predicted	O
+by	O
+using	O
+the	O
+polarity	O
+of	O
+the	O
+QRS	O
+complex	O
+during	O
+sinus	O
+rhythm	O
+on	O
+the	O
+surface	O
+ECG	O
+,	O
+instead	O
+of	O
+the	O
+delta	O
+wave	O
+polarity	O
+as	O
+used	O
+in	O
+many	O
+reports	O
+.	O
+
+The	O
+promoter	O
+mutation	O
+is	O
+complemented	O
+in	O
+trans	O
+by	O
+E1A	B-GENE
+products	O
+of	O
+the	O
+heterologous	O
+helper	O
+adenovirus	O
+type	O
+5	O
+(	O
+Ad5	O
+)	O
+.	O
+
+Thus	O
+,	O
+as	O
+expected	O
+,	O
+trans	O
+-	O
+splicing	O
+depends	O
+on	O
+the	O
+integrity	O
+of	O
+U2	B-GENE
+,	O
+U4	B-GENE
+,	O
+and	O
+U6	B-GENE
+snRNAs	I-GENE
+.	O
+
+Treatment	O
+of	O
+PCC4	O
+.	O
+aza1R	O
+cells	O
+with	O
+an	O
+RAR	B-GENE
+-	O
+selective	O
+agonist	O
+also	O
+repressed	O
+the	O
+expression	O
+of	O
+EC	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+while	O
+treatment	O
+with	O
+an	O
+RXR	B-GENE
+-	O
+selective	O
+agonist	O
+reduced	O
+EC	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+slightly	O
+.	O
+
+Shift	O
+-	O
+down	O
+experiments	O
+indicated	O
+that	O
+the	O
+10	O
+(	O
+4	O
+)	O
+-	O
+to	O
+10	O
+(	O
+5	O
+)	O
+-	O
+fold	O
+reduction	O
+in	O
+virus	O
+yield	O
+at	O
+the	O
+nonpermissive	O
+temperature	O
+was	O
+due	O
+to	O
+the	O
+disfunction	O
+of	O
+alpha	B-GENE
+TIF	I-GENE
+late	O
+in	O
+infection	O
+,	O
+presumably	O
+in	O
+virion	O
+maturation	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+tip	B-GENE
+acts	O
+at	O
+an	O
+early	O
+stage	O
+of	O
+the	O
+T	O
+-	O
+cell	O
+signal	O
+transduction	O
+cascade	O
+by	O
+associating	O
+with	O
+Lck	B-GENE
+and	O
+downregulating	O
+Lck	O
+-	O
+mediated	O
+activation	O
+.	O
+
+Human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+Vpr	I-GENE
+is	O
+a	O
+virion	O
+-	O
+associated	O
+,	O
+regulatory	O
+protein	O
+that	O
+is	O
+required	O
+for	O
+efficient	O
+viral	O
+replication	O
+in	O
+monocytes	O
+/	O
+macrophages	O
+.	O
+
+Here	O
+we	O
+examine	O
+the	O
+potential	O
+for	O
+VP16	B-GENE
+protein	O
+-	O
+protein	O
+interactions	O
+specific	O
+to	O
+virus	O
+-	O
+infected	O
+cells	O
+and	O
+show	O
+that	O
+VP16	B-GENE
+copurifies	O
+in	O
+a	O
+highly	O
+enriched	O
+fraction	O
+with	O
+a	O
+single	O
+major	O
+polypeptide	O
+which	O
+we	O
+identify	O
+as	O
+the	O
+virus	O
+-	O
+encoded	O
+structural	O
+protein	O
+VP22	B-GENE
+.	O
+
+Thus	O
+,	O
+transcriptional	O
+regulation	O
+,	O
+splicing	O
+,	O
+kinase	O
+interaction	O
+sites	O
+,	O
+and	O
+tyrosine	O
+phosphorylation	O
+of	O
+the	O
+LMP2A	B-GENE
+homologs	I-GENE
+have	O
+been	O
+conserved	O
+despite	O
+significant	O
+sequences	O
+heterogeneity	O
+in	O
+the	O
+preterminal	O
+repeat	O
+regions	O
+of	O
+these	O
+human	O
+and	O
+nonhuman	O
+primate	O
+EBVs	O
+.	O
+
+Results	O
+of	O
+the	O
+ECAT	O
+Angina	O
+Pectoris	O
+Study	O
+Group	O
+.	O
+
+Therefore	O
+,	O
+a	O
+prospective	O
+Phase	O
+II	O
+trial	O
+was	O
+conducted	O
+to	O
+determine	O
+the	O
+safety	O
+and	O
+efficacy	O
+of	O
+cryosurgery	O
+following	O
+radiation	O
+therapy	O
+in	O
+men	O
+with	O
+local	O
+recurrence	O
+.	O
+
+These	O
+motifs	O
+include	O
+a	O
+Chi	O
+motif	O
+and	O
+a	O
+Chi	O
+-	O
+like	O
+element	O
+previously	O
+found	O
+in	O
+the	O
+recombination	O
+hotspot	O
+region	O
+of	O
+the	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+and	O
+close	O
+to	O
+chromosomal	O
+breakpoints	O
+in	O
+T	O
+-	O
+ALL	O
+lines	O
+.	O
+
+Common	O
+history	O
+and	O
+prospects	O
+in	O
+surgical	O
+gynecology	O
+of	O
+the	O
+Charite	O
+and	O
+the	O
+Vienna	O
+University	O
+Clinic	O
+
+In	O
+contrast	O
+with	O
+the	O
+previously	O
+reported	O
+HMGR1	B-GENE
+mRNA	I-GENE
+(	O
+HMGR1S	B-GENE
+mRNA	I-GENE
+)	O
+,	O
+which	O
+is	O
+detected	O
+at	O
+high	O
+levels	O
+in	O
+all	O
+tissues	O
+of	O
+the	O
+plant	O
+,	O
+HMGR1L	B-GENE
+mRNA	I-GENE
+is	O
+present	O
+at	O
+relatively	O
+low	O
+levels	O
+and	O
+its	O
+expression	O
+is	O
+restricted	O
+mostly	O
+to	O
+seedlings	O
+,	O
+roots	O
+and	O
+inflorescences	O
+.	O
+
+However	O
+,	O
+the	O
+requirement	O
+of	O
+rev3	B-GENE
+for	O
+the	O
+production	O
+of	O
+G	O
+.	O
+C	O
+-	O
+-	O
+>	O
+T	O
+.	O
+A	O
+transversions	O
+by	O
+the	O
+rad18	B-GENE
+mutator	I-GENE
+,	O
+which	O
+induces	O
+only	O
+these	O
+substitutions	O
+,	O
+was	O
+similar	O
+to	O
+that	O
+for	O
+rad6	B-GENE
+-	O
+mediated	O
+G	O
+.	O
+C	O
+-	O
+-	O
+>	O
+T	O
+.	O
+A	O
+transversion	O
+.	O
+
+The	O
+second	O
+mutation	O
+present	O
+in	O
+the	O
+original	O
+mutant	O
+proved	O
+to	O
+be	O
+an	O
+allele	O
+of	O
+a	O
+known	O
+gene	O
+,	O
+PBS2	B-GENE
+,	O
+which	O
+encodes	O
+a	O
+putative	O
+protein	O
+kinase	O
+that	O
+functions	O
+in	O
+the	O
+high	O
+osmolarity	O
+stress	O
+pathway	O
+.	O
+
+In	O
+adult	O
+tissues	O
+,	O
+it	O
+was	O
+less	O
+restricted	O
+,	O
+indicating	O
+that	O
+RAFTK	B-GENE
+expression	O
+is	O
+developmentally	O
+up	O
+-	O
+regulated	O
+.	O
+
+As	O
+hGM	B-GENE
+-	I-GENE
+CSF	I-GENE
+receptor	I-GENE
+(	O
+hGMR	B-GENE
+)	O
+does	O
+not	O
+contain	O
+a	O
+consensus	O
+sequence	O
+for	O
+binding	O
+of	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+,	O
+hGMR	B-GENE
+must	O
+use	O
+a	O
+distinct	O
+mechanism	O
+for	O
+its	O
+association	O
+with	O
+and	O
+activation	O
+of	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+.	O
+
+J	O
+.	O
+
+The	O
+identity	O
+between	O
+hnRNPs	B-GENE
+H	I-GENE
+and	O
+H	B-GENE
+'	I-GENE
+is	O
+96	O
+%	O
+,	O
+between	O
+H	B-GENE
+and	O
+F	B-GENE
+78	O
+%	O
+,	O
+and	O
+between	O
+H	B-GENE
+'	I-GENE
+and	O
+F	B-GENE
+75	O
+%	O
+,	O
+respectively	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+transiently	O
+expressed	O
+in	O
+primary	O
+cultures	O
+of	O
+rat	O
+hepatocytes	O
+plasmids	O
+consisting	O
+of	O
+CYP3A1	B-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+flanking	I-GENE
+sequences	I-GENE
+fused	O
+to	O
+a	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+reporter	I-GENE
+plasmid	O
+.	O
+
+We	O
+show	O
+that	O
+stimulation	O
+of	O
+resting	O
+splenic	O
+B	O
+cells	O
+with	O
+CD40L	B-GENE
+-	O
+expressing	O
+Sf9	O
+cells	O
+induces	O
+germ	O
+-	O
+line	O
+gamma	O
+1	O
+and	O
+epsilon	O
+transcripts	O
+independently	O
+of	O
+cytokines	O
+.	O
+
+At	O
+the	O
+time	O
+of	O
+the	O
+13	O
+latest	O
+BPVs	O
+,	O
+age	O
+ranged	O
+from	O
+three	O
+days	O
+to	O
+13	O
+.	O
+1	O
+years	O
+(	O
+mean	O
+5	O
+.	O
+7	O
++	O
+/	O
+-	O
+SD	O
+4	O
+.	O
+8	O
+years	O
+)	O
+.	O
+
+A	O
+tobacco	O
+homologue	O
+(	O
+trolC	B-GENE
+)	O
+of	O
+the	O
+rolC	B-GENE
+gene	I-GENE
+of	I-GENE
+the	I-GENE
+Agrobacterium	I-GENE
+rhizogenes	I-GENE
+Ri	I-GENE
+-	I-GENE
+plasmid	I-GENE
+was	O
+cloned	O
+and	O
+sequenced	O
+from	O
+Nicotiana	O
+tabacum	O
+L	O
+.	O
+cv	O
+.	O
+
+High	O
+ADR1	B-GENE
+gene	I-GENE
+dosage	O
+increased	O
+the	O
+transcription	O
+of	O
+genes	O
+encoding	O
+peroxisomal	O
+proteins	O
+as	O
+compared	O
+to	O
+one	O
+copy	O
+of	O
+the	O
+ADR1	B-GENE
+gene	I-GENE
+.	O
+
+Of	O
+the	O
+three	O
+known	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+family	I-GENE
+inhibitors	O
+,	O
+Ig	B-GENE
+/	I-GENE
+EBP	I-GENE
+,	O
+LIP	B-GENE
+and	O
+CHOP	B-GENE
+-	I-GENE
+10	I-GENE
+,	O
+only	O
+Ig	B-GENE
+/	I-GENE
+EBP	I-GENE
+is	O
+ubiquitously	O
+expressed	O
+.	O
+
+The	O
+effects	O
+of	O
+a	O
+1	O
+-	O
+or	O
+24	O
+-	O
+hour	O
+pretreatment	O
+regimen	O
+with	O
+monophosphoryl	O
+lipid	O
+A	O
+(	O
+MLA	O
+,	O
+35	O
+micrograms	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+on	O
+myocardial	O
+stunning	O
+produced	O
+by	O
+repetitive	O
+coronary	O
+occlusions	O
+were	O
+studied	O
+in	O
+barbital	O
+-	O
+anesthetized	O
+dogs	O
+.	O
+
+A	O
+platelet	B-GENE
+-	I-GENE
+derived	I-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+(	O
+PDGF	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+phosphopeptide	O
+containing	O
+Tyr	O
+-	O
+857	O
+does	O
+not	O
+bind	O
+appreciably	O
+to	O
+the	O
+Src	B-GENE
+SH2	I-GENE
+domain	I-GENE
+,	O
+suggesting	O
+it	O
+is	O
+not	O
+the	O
+PDGF	B-GENE
+-	I-GENE
+R	I-GENE
+binding	O
+site	O
+for	O
+Src	B-GENE
+as	O
+previously	O
+reported	O
+.	O
+
+We	O
+have	O
+also	O
+tested	O
+Src	B-GENE
+SH2	B-GENE
+mutants	O
+for	O
+their	O
+binding	O
+properties	O
+and	O
+have	O
+interpreted	O
+our	O
+results	O
+in	O
+light	O
+of	O
+the	O
+recent	O
+crystal	O
+structure	O
+solution	O
+for	O
+the	O
+Src	B-GENE
+SH2	B-GENE
+domain	O
+.	O
+
+These	O
+observations	O
+link	O
+actin	B-GENE
+plaque	O
+assembly	O
+to	O
+increased	O
+cell	O
+substrate	O
+adhesion	O
+.	O
+
+The	O
+early	O
+lethality	O
+of	O
+the	O
+left	O
+-	O
+sided	O
+resectio	O
+was	O
+0	O
+%	O
+and	O
+the	O
+postoperative	O
+survival	O
+-	O
+-	O
+5	O
+-	O
+10	O
+months	O
+.	O
+
+There	O
+are	O
+two	O
+immunogenic	O
+sites	O
+on	O
+the	O
+type	O
+A	O
+influenza	O
+A	O
+/	O
+Japan	O
+/	O
+57	O
+(	O
+H2N2	O
+)	O
+hemagglutinin	B-GENE
+(	O
+HA	B-GENE
+)	O
+that	O
+can	O
+be	O
+recognized	O
+by	O
+class	B-GENE
+I	I-GENE
+major	I-GENE
+histocompatibility	I-GENE
+complex	I-GENE
+(	O
+MHC	B-GENE
+)	O
+,	O
+H	B-GENE
+-	I-GENE
+2Kd	I-GENE
+-	O
+restricted	O
+cytolytic	O
+T	O
+lymphocytes	O
+(	O
+CTLs	O
+)	O
+.	O
+
+This	O
+enhancer	O
+activates	O
+both	O
+the	O
+K19	B-GENE
+and	O
+TK	B-GENE
+basal	I-GENE
+promoters	I-GENE
+in	O
+HeLa	O
+cells	O
+.	O
+
+Interestingly	O
+,	O
+one	O
+IRF	B-GENE
+binding	I-GENE
+site	I-GENE
+was	O
+found	O
+within	O
+the	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+promoter	I-GENE
+,	O
+and	O
+expression	O
+of	O
+the	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+was	O
+affected	O
+by	O
+both	O
+transient	O
+and	O
+stable	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+.	O
+
+Therefore	O
+,	O
+we	O
+studied	O
+ninety	O
+coagulopathic	O
+patients	O
+with	O
+the	O
+aim	O
+of	O
+determining	O
+the	O
+prevalence	O
+of	O
+hepatitis	B-GENE
+C	I-GENE
+virus	I-GENE
+(	I-GENE
+HCV	I-GENE
+)	I-GENE
+antibodies	I-GENE
+using	O
+the	O
+ELISA	O
+and	O
+RIBA	O
+methods	O
+.	O
+
+The	O
+highest	O
+decrease	O
+in	O
+mutagenic	O
+activity	O
+was	O
+observed	O
+when	O
+enzymatic	O
+bleaching	O
+was	O
+used	O
+together	O
+with	O
+chlorine	O
+.	O
+
+There	O
+was	O
+also	O
+a	O
+highly	O
+significant	O
+correlation	O
+between	O
+total	O
+selenium	O
+intake	O
+and	O
+liver	O
+selenium	O
+concentration	O
+(	O
+r	O
+=	O
+0	O
+.	O
+99	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+after	O
+1	O
+mo	O
+of	O
+treatment	O
+,	O
+but	O
+this	O
+time	O
+liver	O
+selenium	O
+did	O
+not	O
+change	O
+with	O
+time	O
+,	O
+and	O
+the	O
+correlation	O
+remained	O
+highly	O
+significant	O
+throughout	O
+the	O
+investigation	O
+.	O
+
+Antibodies	O
+affinity	O
+-	O
+purified	O
+using	O
+the	O
+bacterially	O
+expressed	O
+recombinant	O
+protein	O
+recognized	O
+the	O
+56K	B-GENE
+autoantigen	I-GENE
+in	O
+a	O
+HeLa	O
+cell	O
+extract	O
+.	O
+cDNA	O
+sequencing	O
+revealed	O
+that	O
+the	O
+56K	B-GENE
+cDNA	I-GENE
+shares	O
+a	O
+high	O
+degree	O
+of	O
+homology	O
+in	O
+both	O
+nucleotide	O
+(	O
+87	O
+%	O
+)	O
+and	O
+amino	O
+acid	O
+sequence	O
+(	O
+92	O
+.	O
+5	O
+%	O
+)	O
+with	O
+bovine	B-GENE
+annexin	I-GENE
+XI	I-GENE
+,	O
+indicating	O
+that	O
+the	O
+56K	B-GENE
+cDNA	I-GENE
+encodes	O
+the	O
+human	B-GENE
+homologue	I-GENE
+of	I-GENE
+annexin	I-GENE
+XI	I-GENE
+,	O
+a	O
+member	O
+of	O
+the	O
+Ca	B-GENE
+(	I-GENE
+2	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+dependent	I-GENE
+phospholipid	I-GENE
+binding	I-GENE
+protein	I-GENE
+family	I-GENE
+.	O
+
+The	O
+avidin	B-GENE
+-	I-GENE
+biotin	I-GENE
+complex	I-GENE
+peroxidase	I-GENE
+(	O
+ABC	B-GENE
+-	I-GENE
+P	I-GENE
+)	O
+method	O
+was	O
+used	O
+to	O
+detect	O
+Mycobacterium	O
+bovis	O
+,	O
+and	O
+the	O
+results	O
+were	O
+compared	O
+with	O
+those	O
+obtained	O
+by	O
+the	O
+Ziehl	O
+-	O
+Neelsen	O
+(	O
+ZN	O
+)	O
+technique	O
+.	O
+
+Its	O
+role	O
+in	O
+these	O
+processes	O
+suggests	O
+that	O
+the	O
+function	O
+of	O
+c	B-GENE
+-	I-GENE
+Myb	I-GENE
+may	O
+be	O
+important	O
+early	O
+in	O
+the	O
+establishment	O
+of	O
+the	O
+hematopoietic	O
+lineage	O
+.	O
+
+The	O
+transforming	O
+gene	O
+of	O
+the	O
+avian	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+CT10	I-GENE
+encodes	O
+a	O
+fusion	O
+protein	O
+(	O
+p47gag	B-GENE
+-	O
+crk	B-GENE
+or	O
+v	B-GENE
+-	I-GENE
+Crk	I-GENE
+)	O
+containing	O
+viral	B-GENE
+Gag	I-GENE
+sequences	I-GENE
+fused	O
+to	O
+cellular	O
+sequences	O
+consisting	O
+primarily	O
+of	O
+Src	B-GENE
+homology	I-GENE
+regions	I-GENE
+2	I-GENE
+and	I-GENE
+3	I-GENE
+(	O
+SH2	B-GENE
+and	O
+SH3	B-GENE
+sequences	I-GENE
+)	O
+.	O
+
+This	O
+specific	O
+methylation	O
+pattern	O
+caused	O
+inactivation	O
+of	O
+the	O
+HSV	B-GENE
+tk	I-GENE
+gene	I-GENE
+,	O
+while	O
+methylation	O
+of	O
+the	O
+cytosine	O
+residues	O
+within	O
+the	O
+nucleotide	O
+sequence	O
+from	O
++	O
+811	O
+to	O
++	O
+1309	O
+had	O
+no	O
+effect	O
+on	O
+HSV	B-GENE
+tk	I-GENE
+gene	I-GENE
+activity	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+study	O
+documents	O
+that	O
+regression	O
+of	O
+choroidal	O
+neovascularization	O
+that	O
+occurred	O
+with	O
+alpha	B-GENE
+interferon	I-GENE
+treatment	O
+was	O
+minimal	O
+.	O
+
+Long	O
+-	O
+range	O
+mapping	O
+of	O
+the	O
+11q23	O
+region	O
+involved	O
+in	O
+chromosome	O
+aberrations	O
+in	O
+human	O
+tumors	O
+by	O
+pulsed	O
+-	O
+field	O
+gel	O
+electrophoresis	O
+with	O
+a	O
+yeast	O
+artificial	O
+chromosome	O
+.	O
+
+GTRE	O
+,	O
+TRE	O
+,	O
+and	O
+CRE	O
+oligonucleotides	O
+all	O
+compete	O
+more	O
+efficiently	O
+for	O
+protein	O
+binding	O
+to	O
+their	O
+labeled	O
+congeners	O
+than	O
+for	O
+protein	O
+binding	O
+to	O
+either	O
+of	O
+the	O
+other	O
+labeled	O
+oligonucleotides	O
+,	O
+suggesting	O
+that	O
+the	O
+GTRE	O
+,	O
+TRE	O
+,	O
+and	O
+CRE	O
+oligonucleotides	O
+,	O
+suggesting	O
+that	O
+the	O
+GTRE	O
+,	O
+TRE	O
+,	O
+and	O
+CRE	O
+oligonucleotides	O
+each	O
+bind	O
+unique	O
+as	O
+well	O
+as	O
+common	O
+proteins	O
+,	O
+likely	O
+to	O
+be	O
+members	O
+of	O
+the	O
+Jun	B-GENE
+/	O
+Fos	B-GENE
+and	O
+cAMP	B-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+/	O
+activating	B-GENE
+transcription	I-GENE
+factors	I-GENE
+(	O
+CREB	B-GENE
+/	O
+ATF	B-GENE
+)	O
+families	O
+of	O
+transcription	O
+factors	O
+,	O
+in	O
+chromaffin	O
+cells	O
+.	O
+
+One	O
+patient	O
+only	O
+had	O
+any	O
+test	O
+abnormalities	O
+.	O
+
+One	O
+antibody	O
+,	O
+mAb1C2	B-GENE
+,	O
+and	O
+a	O
+synthetic	O
+peptide	O
+comprising	O
+its	O
+epitope	O
+selectively	O
+inhibited	O
+in	O
+vitro	O
+transcription	O
+from	O
+TATA	O
+-	O
+containing	O
+,	O
+but	O
+not	O
+from	O
+TATA	O
+-	O
+less	O
+promoters	O
+,	O
+irrespective	O
+of	O
+whether	O
+they	O
+were	O
+transcribed	O
+by	O
+Pol	B-GENE
+II	I-GENE
+or	O
+Pol	B-GENE
+III	I-GENE
+.	O
+
+The	O
+lymph	O
+nodes	O
+from	O
+two	O
+of	O
+the	O
+patients	O
+with	O
+rheumatoid	O
+arthritis	O
+contained	O
+numerous	O
+sarcoid	O
+like	O
+granulomata	O
+,	O
+further	O
+indicating	O
+a	O
+possible	O
+association	O
+between	O
+sarcoidosis	O
+and	O
+rheumatoid	O
+arthritis	O
+.	O
+
+HCV	O
+infection	O
+acquired	O
+during	O
+or	O
+after	O
+BMT	O
+caused	O
+only	O
+mild	O
+acute	O
+hepatitis	O
+C	O
+,	O
+which	O
+progressed	O
+to	O
+chronic	O
+hepatitis	O
+C	O
+in	O
+one	O
+patient	O
+surviving	O
+10	O
+years	O
+after	O
+BMT	O
+.	O
+
+Hepatitis	O
+C	O
+virus	O
+infection	O
+is	O
+a	O
+risk	O
+factor	O
+for	O
+liver	O
+failure	O
+from	O
+veno	O
+-	O
+occlusive	O
+disease	O
+after	O
+bone	O
+marrow	O
+transplantation	O
+.	O
+
+High	O
+plasma	O
+concentrations	O
+of	O
+soluble	O
+E	B-GENE
+-	I-GENE
+selectin	I-GENE
+were	O
+closely	O
+associated	O
+with	O
+multiple	O
+-	O
+organ	O
+dysfunction	O
+and	O
+death	O
+.	O
+
+These	O
+human	O
+IFN	B-GENE
+-	I-GENE
+beta	I-GENE
+-	O
+transformed	O
+cell	O
+populations	O
+have	O
+acquired	O
+a	O
+low	O
+,	O
+constitutive	O
+production	O
+of	O
+human	B-GENE
+IFN	I-GENE
+,	O
+while	O
+replicating	O
+at	O
+a	O
+rate	O
+similar	O
+to	O
+that	O
+of	O
+untransformed	O
+cells	O
+and	O
+of	O
+cells	O
+transformed	O
+with	O
+the	O
+control	O
+vector	O
+carrying	O
+a	O
+human	B-GENE
+IFN	I-GENE
+-	I-GENE
+beta	I-GENE
+sequence	I-GENE
+encoding	O
+an	O
+inactive	O
+,	O
+mutated	O
+protein	O
+.	O
+
+Improvement	O
+of	O
+the	O
+polypyrimidine	O
+tract	O
+also	O
+increased	O
+the	O
+splicing	O
+efficiency	O
+,	O
+but	O
+to	O
+a	O
+degree	O
+slightly	O
+less	O
+than	O
+that	O
+obtained	O
+with	O
+the	O
+branchpoint	O
+mutation	O
+.	O
+
+Activation	O
+of	O
+the	O
+SH2	B-GENE
+-	I-GENE
+containing	I-GENE
+protein	I-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+,	O
+SH	B-GENE
+-	I-GENE
+PTP2	I-GENE
+,	O
+by	O
+phosphotyrosine	O
+-	O
+containing	O
+peptides	O
+derived	O
+from	O
+insulin	B-GENE
+receptor	I-GENE
+substrate	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+injection	O
+of	O
+a	O
+plasmid	O
+encoding	O
+simian	B-GENE
+virus	I-GENE
+40	I-GENE
+small	I-GENE
+t	I-GENE
+antigen	I-GENE
+,	O
+which	O
+interacts	O
+with	O
+PP2A	B-GENE
+to	O
+inhibit	O
+its	O
+activity	O
+towards	O
+several	O
+phosphoprotein	O
+substrates	O
+,	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+phosphorylation	O
+state	O
+of	O
+CREB	B-GENE
+in	O
+stimulated	O
+or	O
+unstimulated	O
+NIH	O
+3T3	O
+cells	O
+.	O
+
+Several	O
+Src	B-GENE
+SH3	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+were	O
+phosphorylated	O
+in	O
+Src	B-GENE
+-	O
+transformed	O
+cells	O
+.	O
+
+We	O
+also	O
+examined	O
+the	O
+effect	O
+of	O
+proteolytic	O
+processing	O
+in	O
+the	O
+MVE	O
+nonstructural	O
+polyprotein	O
+segment	O
+mediated	O
+by	O
+the	O
+viral	B-GENE
+proteinase	I-GENE
+NS3	I-GENE
+on	O
+antigen	O
+processing	O
+and	O
+presentation	O
+of	O
+the	O
+MVE	O
+H	O
+-	O
+2Kk	O
+-	O
+restricted	O
+T	O
+cell	O
+determinant	O
+.	O
+
+A	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+PRL	I-GENE
+receptor	I-GENE
+(	O
+PRLR	B-GENE
+)	O
+complementary	O
+DNA	O
+from	O
+pigeons	O
+was	O
+obtained	O
+by	O
+screening	O
+pigeon	O
+crop	O
+sac	O
+libraries	O
+and	O
+by	O
+reverse	O
+transcription	O
+coupled	O
+with	O
+polymerase	O
+chain	O
+reaction	O
+.	O
+
+After	O
+7	O
+days	O
+,	O
+a	O
+spontaneous	O
+regression	O
+of	O
+the	O
+morphologic	O
+alterations	O
+caused	O
+by	O
+caerulein	O
+-	O
+induced	O
+acute	O
+pancreatitis	O
+occurs	O
+;	O
+however	O
+,	O
+recovery	O
+of	O
+the	O
+secretory	O
+function	O
+of	O
+the	O
+pancreas	O
+was	O
+only	O
+reached	O
+after	O
+this	O
+period	O
+of	O
+time	O
+when	O
+L	O
+-	O
+364	O
+,	O
+718	O
+was	O
+administered	O
+therapeutically	O
+(	O
+0	O
+.	O
+1	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+)	O
+.	O
+
+We	O
+observed	O
+that	O
+dephosphorylation	O
+severely	O
+inhibits	O
+the	O
+DNA	O
+-	O
+binding	O
+ability	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+-	I-GENE
+delta	I-GENE
+and	O
+its	O
+transactivating	O
+potential	O
+increases	O
+in	O
+the	O
+presence	O
+of	O
+cellular	O
+phosphatase	O
+inhibitors	O
+,	O
+such	O
+as	O
+okadaic	O
+acid	O
+and	O
+sodium	O
+orthovanadate	O
+.	O
+
+Two	O
+promoters	O
+were	O
+identified	O
+by	O
+S1	B-GENE
+nuclease	I-GENE
+mapping	O
+:	O
+P1	O
+,	O
+which	O
+lies	O
+about	O
+72	O
+bp	O
+upstream	O
+from	O
+the	O
+structural	O
+gene	O
+;	O
+and	O
+P2	O
+,	O
+which	O
+lies	O
+about	O
+35	O
+bp	O
+upstream	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+cells	O
+containing	O
+a	O
+PTP1C	B-GENE
+in	O
+which	O
+the	O
+catalytic	O
+site	O
+had	O
+been	O
+inactivated	O
+through	O
+mutagenesis	O
+,	O
+stably	O
+phosphorylated	O
+the	O
+phosphatase	O
+.	O
+
+We	O
+recently	O
+found	O
+that	O
+the	O
+p72syk	B-GENE
+protein	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+is	O
+physically	O
+associated	O
+with	O
+the	O
+TCR	B-GENE
+/	O
+CD3	B-GENE
+complex	O
+and	O
+is	O
+rapidly	O
+tyrosine	O
+phosphorylated	O
+and	O
+activated	O
+by	O
+receptor	O
+triggering	O
+also	O
+in	O
+T	O
+cells	O
+lacking	O
+p56lck	B-GENE
+.	O
+
+The	O
+transforming	O
+protein	O
+of	O
+Rous	O
+sarcoma	O
+virus	O
+,	O
+pp60v	B-GENE
+-	I-GENE
+src	I-GENE
+,	O
+and	O
+its	O
+normal	O
+cellular	O
+homolog	O
+,	O
+pp60c	B-GENE
+-	I-GENE
+src	I-GENE
+,	O
+differ	O
+not	O
+only	O
+in	O
+oncogenic	O
+potential	O
+but	O
+also	O
+in	O
+their	O
+subcellular	O
+localization	O
+and	O
+cytoskeletal	O
+binding	O
+ability	O
+.	O
+pp60v	B-GENE
+-	I-GENE
+src	I-GENE
+has	O
+been	O
+shown	O
+to	O
+stably	O
+associate	O
+with	O
+a	O
+detergent	O
+-	O
+insoluble	O
+cytoskeletal	O
+matrix	O
+,	O
+whereas	O
+pp60c	B-GENE
+-	I-GENE
+src	I-GENE
+does	O
+not	O
+.	O
+
+Organization	O
+of	O
+the	O
+bovine	O
+gene	O
+encoding	O
+the	O
+endothelial	B-GENE
+nitric	I-GENE
+oxide	I-GENE
+synthase	I-GENE
+.	O
+
+We	O
+determined	O
+whether	O
+regional	O
+myocardial	O
+work	O
+efficiency	O
+(	O
+segment	O
+work	O
+/	O
+regional	O
+O2	O
+consumption	O
+)	O
+would	O
+be	O
+elevated	O
+by	O
+surgically	O
+-	O
+augmented	O
+inflow	O
+.	O
+
+In	O
+female	O
+Sl	B-GENE
+(	I-GENE
+pan	I-GENE
+)	I-GENE
+/	I-GENE
+Sl	I-GENE
+(	I-GENE
+pan	I-GENE
+)	I-GENE
+mice	O
+,	O
+ovarian	O
+follicle	O
+development	O
+is	O
+arrested	O
+at	O
+the	O
+one	O
+layered	O
+cuboidal	O
+stage	O
+as	O
+a	O
+result	O
+of	O
+reduced	O
+KL	B-GENE
+expression	O
+in	O
+follicle	O
+cells	O
+,	O
+indicating	O
+a	O
+role	O
+for	O
+c	B-GENE
+-	I-GENE
+kit	I-GENE
+in	O
+oocyte	O
+growth	O
+.	O
+
+Anti	B-GENE
+-	I-GENE
+NPROSP	I-GENE
+-	I-GENE
+C	I-GENE
+also	O
+exclusively	O
+detected	O
+time	O
+-	O
+dependent	O
+appearances	O
+of	O
+5	B-GENE
+-	I-GENE
+10	I-GENE
+-	I-GENE
+kDa	I-GENE
+proSP	I-GENE
+-	I-GENE
+C	I-GENE
+forms	O
+in	O
+lamellar	O
+bodies	O
+and	O
+homogenates	O
+.	O
+
+In	O
+the	O
+B6	O
+-	O
+derived	O
+Db	B-GENE
+mutant	I-GENE
+B6	I-GENE
+.	I-GENE
+CH	I-GENE
+-	I-GENE
+2bm13	I-GENE
+(	I-GENE
+bm13	I-GENE
+)	I-GENE
+strain	O
+,	O
+part	O
+of	O
+the	O
+class	B-GENE
+I	I-GENE
+Db	I-GENE
+antigen	I-GENE
+-	I-GENE
+presenting	I-GENE
+groove	I-GENE
+is	O
+shaped	O
+by	O
+a	O
+class	B-GENE
+I	I-GENE
+Kb	I-GENE
+-	I-GENE
+encoded	I-GENE
+sequence	I-GENE
+.	O
+
+Our	O
+findings	O
+confirm	O
+the	O
+high	O
+frequency	O
+of	O
+proximal	O
+nerve	O
+lesions	O
+in	O
+early	O
+GBS	O
+and	O
+CIDP	O
+,	O
+not	O
+all	O
+of	O
+which	O
+are	O
+associated	O
+with	O
+distal	O
+motor	O
+conduction	O
+abnormalities	O
+,	O
+and	O
+suggest	O
+that	O
+assessment	O
+of	O
+multiple	O
+F	O
+wave	O
+parameters	O
+,	O
+in	O
+particular	O
+chronodispersion	O
+,	O
+mean	O
+latency	O
+and	O
+mean	O
+amplitude	O
+(	O
+in	O
+addition	O
+to	O
+absence	O
+and	O
+minimum	O
+latency	O
+)	O
+,	O
+increases	O
+the	O
+yield	O
+of	O
+F	O
+wave	O
+studies	O
+.	O
+
+Effects	O
+of	O
+alterations	O
+of	O
+primer	O
+-	O
+binding	O
+site	O
+sequences	O
+on	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+replication	O
+.	O
+
+Presentation	O
+of	O
+a	O
+horse	B-GENE
+cytochrome	I-GENE
+c	I-GENE
+peptide	I-GENE
+by	O
+multiple	O
+H	B-GENE
+-	I-GENE
+2b	I-GENE
+class	I-GENE
+I	I-GENE
+major	I-GENE
+histocompatibility	I-GENE
+complex	I-GENE
+(	O
+MHC	B-GENE
+)	O
+molecules	O
+to	O
+C57BL	O
+/	O
+6	O
+-	O
+and	O
+bm1	O
+-	O
+derived	O
+cytotoxic	O
+T	O
+lymphocytes	O
+:	O
+presence	O
+of	O
+a	O
+single	O
+MHC	B-GENE
+anchor	I-GENE
+residue	I-GENE
+may	O
+confer	O
+efficient	O
+peptide	O
+-	O
+specific	O
+CTL	O
+recognition	O
+.	O
+
+Diagnosis	O
+of	O
+prostatic	O
+carcinoma	O
+:	O
+the	O
+yield	O
+of	O
+serum	B-GENE
+prostate	I-GENE
+specific	I-GENE
+antigen	I-GENE
+,	O
+digital	O
+rectal	O
+examination	O
+and	O
+transrectal	O
+ultrasonography	O
+.	O
+
+Increased	O
+granulocyte	B-GENE
+-	I-GENE
+colony	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+levels	O
+in	O
+neonates	O
+with	O
+perinatal	O
+complications	O
+.	O
+
+The	O
+results	O
+revealed	O
+a	O
+hierarchy	O
+of	O
+ligand	O
+affinities	O
+that	O
+mirrored	O
+their	O
+adhesive	O
+activity	O
+(	O
+rsVCAM	B-GENE
+-	I-GENE
+1	I-GENE
+>	O
+fibronectin	B-GENE
+variants	I-GENE
+containing	O
+CS1	B-GENE
+>	O
+>	O
+other	O
+fibronectin	B-GENE
+variants	I-GENE
+)	O
+.	O
+
+When	O
+expressed	O
+in	O
+and	O
+purified	O
+from	O
+Escherichia	O
+coli	O
+,	O
+both	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+Fpr3	I-GENE
+and	O
+its	O
+isolated	O
+COOH	O
+-	O
+terminal	O
+domain	O
+exhibit	O
+readily	O
+detectable	O
+PPIase	B-GENE
+activity	O
+.	O
+
+However	O
+,	O
+expression	O
+of	O
+sigma	B-GENE
+3	I-GENE
+from	O
+S4	B-GENE
+(	O
+3	B-GENE
+'	I-GENE
+UTR	I-GENE
+/	I-GENE
+S1	I-GENE
+)	O
+,	O
+which	O
+included	O
+the	O
+PKR	B-GENE
+activator	I-GENE
+sequence	I-GENE
+from	O
+S1	B-GENE
+within	O
+the	O
+3	B-GENE
+'	I-GENE
+-	I-GENE
+UTR	I-GENE
+of	I-GENE
+S4	I-GENE
+,	O
+was	O
+comparable	O
+to	O
+that	O
+from	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+S4	I-GENE
+.	O
+
+Microvessels	O
+were	O
+counted	O
+in	O
+a	O
+x200	O
+field	O
+(	O
+0	O
+.	O
+754	O
+mm2	O
+)	O
+in	O
+the	O
+area	O
+of	O
+maximal	O
+angiogenesis	O
+.	O
+
+Recent	O
+studies	O
+have	O
+demonstrated	O
+that	O
+the	O
+activated	O
+GH	B-GENE
+receptor	I-GENE
+can	O
+stimulate	O
+Stat1	B-GENE
+,	O
+a	O
+cytoplasmic	O
+transcription	O
+factor	O
+that	O
+becomes	O
+tyrosine	O
+phosphorylated	O
+and	O
+translocates	O
+to	O
+the	O
+nucleus	O
+,	O
+where	O
+it	O
+can	O
+interact	O
+with	O
+specific	O
+DNA	O
+sequences	O
+to	O
+modulate	O
+gene	O
+expression	O
+.	O
+
+In	O
+viral	O
+infections	O
+,	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+was	O
+correlated	O
+with	O
+mononuclear	O
+cells	O
+(	O
+rs	O
+=	O
+0	O
+.	O
+41	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+white	O
+blood	O
+cell	O
+counts	O
+(	O
+rs	O
+=	O
+0	O
+.	O
+56	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+neutrophils	O
+(	O
+rs	O
+=	O
+0	O
+.	O
+41	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+and	O
+CRP	B-GENE
+(	O
+rs	O
+=	O
+0	O
+.	O
+47	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Minor	O
+initiation	O
+sites	O
+were	O
+found	O
+at	O
+positions	O
+-	O
+128	O
+,	O
+-	O
+111	O
+,	O
+-	O
+91	O
+,	O
+and	O
+-	O
+74	O
+.	O
+
+Phosphoamino	O
+acid	O
+analysis	O
+of	O
+radiolabeled	O
+ASGPR	B-GENE
+subunits	I-GENE
+identified	O
+Ser	O
+(	O
+P	O
+)	O
+as	O
+the	O
+predominant	O
+(	O
+approximately	O
+95	O
+%	O
+)	O
+and	O
+Thr	O
+(	O
+P	O
+)	O
+as	O
+a	O
+minor	O
+(	O
+approximately	O
+5	O
+%	O
+)	O
+phosphoamino	O
+acid	O
+in	O
+each	O
+polypeptide	O
+and	O
+confirmed	O
+the	O
+presence	O
+of	O
+Tyr	O
+(	O
+P	O
+)	O
+(	O
+approximately	O
+1	O
+%	O
+)	O
+in	O
+RHL1	B-GENE
+.	O
+
+To	O
+further	O
+define	O
+the	O
+structural	O
+requirements	O
+for	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+interaction	O
+with	O
+the	O
+TCR	B-GENE
+,	O
+we	O
+developed	O
+a	O
+binding	O
+assay	O
+using	O
+immobilized	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+fusion	I-GENE
+proteins	I-GENE
+containing	O
+the	O
+NH2	O
+-	O
+and	O
+/	O
+or	O
+COOH	B-GENE
+-	I-GENE
+terminal	I-GENE
+SH2	I-GENE
+domains	I-GENE
+of	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+,	O
+and	O
+soluble	O
+synthetic	O
+peptides	O
+with	O
+the	O
+sequence	O
+of	O
+the	O
+cytoplasmic	O
+region	O
+of	O
+the	O
+TCR	B-GENE
+zeta	I-GENE
+chain	I-GENE
+(	O
+TCR	B-GENE
+zeta	I-GENE
+cyt	I-GENE
+)	O
+or	O
+individual	O
+TCR	B-GENE
+zeta	I-GENE
+and	O
+CD3	B-GENE
+epsilon	I-GENE
+TAM	I-GENE
+motifs	I-GENE
+.	O
+
+All	O
+four	O
+doubly	O
+tyrosine	O
+phosphorylated	O
+TAM	O
+peptides	O
+cross	O
+-	O
+compete	O
+with	O
+each	O
+other	O
+for	O
+binding	O
+to	O
+the	O
+tandem	O
+SH2	B-GENE
+domains	I-GENE
+of	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+.	O
+
+The	O
+three	O
+-	O
+dimensional	O
+structure	O
+of	O
+RT	B-GENE
+shows	O
+that	O
+it	O
+is	O
+a	O
+strikingly	O
+asymmetric	O
+heterodimer	O
+consisting	O
+of	O
+two	O
+differently	O
+folded	O
+subunits	O
+(	O
+molecular	O
+weights	O
+66	O
+kDa	O
+and	O
+51	O
+kDa	O
+)	O
+with	O
+identical	O
+amino	O
+-	O
+terminal	O
+amino	O
+acid	O
+sequences	O
+(	O
+residues	O
+1	O
+-	O
+428	O
+)	O
+.	O
+
+Pharmacological	O
+and	O
+pharmacokinetic	O
+characteristics	O
+of	O
+the	O
+non	O
+-	O
+ionic	O
+monomeric	O
+X	O
+-	O
+ray	O
+contrast	O
+agent	O
+iopromide	O
+(	O
+Ultravist	O
+,	O
+CAS	O
+73334	O
+-	O
+07	O
+-	O
+3	O
+)	O
+were	O
+evaluated	O
+in	O
+preclinical	O
+studies	O
+.	O
+
+All	O
+subsequent	O
+patients	O
+were	O
+treated	O
+at	O
+the	O
+maximal	O
+tolerated	O
+dose	O
+of	O
+EDXR	O
+(	O
+35	O
+mg	O
+/	O
+m2	O
+/	O
+day	O
+)	O
+.	O
+
+Addition	O
+of	O
+soluble	O
+recombinant	B-GENE
+human	I-GENE
+SLF	I-GENE
+to	O
+SI4	O
+-	O
+h220	O
+cultures	O
+enhanced	O
+reduction	O
+of	O
+cell	O
+-	O
+surface	O
+c	B-GENE
+-	I-GENE
+kit	I-GENE
+expression	O
+and	O
+its	O
+protein	O
+degradation	O
+.	O
+
+Membrane	O
+-	O
+bound	O
+Steel	B-GENE
+factor	I-GENE
+induces	O
+more	O
+persistent	O
+tyrosine	B-GENE
+kinase	I-GENE
+activation	O
+and	O
+longer	O
+life	O
+span	O
+of	O
+c	B-GENE
+-	I-GENE
+kit	I-GENE
+gene	O
+-	O
+encoded	O
+protein	O
+than	O
+its	O
+soluble	O
+form	O
+.	O
+
+Analysis	O
+of	O
+the	O
+sequences	O
+with	O
+the	O
+BLAST	O
+and	O
+GRAIL	O
+programs	O
+provided	O
+additional	O
+independent	O
+evidence	O
+that	O
+15	O
+of	O
+these	O
+17	O
+clones	O
+contain	O
+coding	O
+sequences	O
+and	O
+that	O
+nine	O
+other	O
+clones	O
+are	O
+likely	O
+to	O
+contain	O
+sequences	O
+coding	O
+for	O
+portions	O
+of	O
+new	O
+genes	O
+.	O
+
+Patients	O
+with	O
+more	O
+than	O
+250	O
+PVC	O
+/	O
+24	O
+hours	O
+were	O
+selected	O
+for	O
+distribution	O
+of	O
+PVC	O
+and	O
+CI	O
+evaluation	O
+.	O
+
+Horvath	O
+,	O
+I	O
+.	O
+
+Cell	O
+lines	O
+derived	O
+from	O
+the	O
+tumors	O
+were	O
+examined	O
+by	O
+fluorescent	O
+in	O
+situ	O
+hybridization	O
+for	O
+the	O
+status	O
+of	O
+the	O
+transferred	O
+human	O
+chromosome	O
+and	O
+by	O
+PCR	O
+for	O
+marker	O
+loss	O
+.	O
+
+However	O
+,	O
+multiple	O
+alanine	O
+substitutions	O
+or	O
+proline	O
+(	O
+helix	O
+-	O
+destabilizing	O
+)	O
+substitutions	O
+disrupted	O
+both	O
+oligomerization	O
+and	O
+transport	O
+of	O
+GP64	B-GENE
+EFP	I-GENE
+.	O
+
+The	O
+FinO	B-GENE
+protein	I-GENE
+of	O
+IncF	O
+plasmids	O
+binds	O
+FinP	B-GENE
+antisense	I-GENE
+RNA	I-GENE
+and	O
+its	O
+target	O
+,	O
+traJ	B-GENE
+mRNA	I-GENE
+,	O
+and	O
+promotes	O
+duplex	O
+formation	O
+.	O
+
+We	O
+linked	O
+a	O
+4	O
+.	O
+1	O
+-	O
+kilobase	O
+pair	O
+HindIII	B-GENE
+DNA	I-GENE
+fragment	I-GENE
+from	O
+the	O
+region	O
+upstream	O
+of	O
+the	O
+human	B-GENE
+AP	I-GENE
+endonuclease	I-GENE
+gene	I-GENE
+(	O
+APE	B-GENE
+)	O
+to	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+gene	O
+.	O
+
+The	O
+overexpressed	O
+His6	B-GENE
+-	I-GENE
+tagged	I-GENE
+GrsA	I-GENE
+derivatives	I-GENE
+were	O
+affinity	O
+-	O
+purified	O
+,	O
+and	O
+the	O
+catalytic	O
+properties	O
+of	O
+the	O
+deletion	O
+mutants	O
+were	O
+examined	O
+by	O
+biochemical	O
+studies	O
+including	O
+ATP	O
+-	O
+dependent	O
+amino	O
+acid	O
+activation	O
+,	O
+carboxyl	O
+thioester	O
+formation	O
+,	O
+and	O
+the	O
+ability	O
+to	O
+racemize	O
+the	O
+covalently	O
+bound	O
+phenylalanine	O
+from	O
+L	O
+-	O
+to	O
+the	O
+D	O
+-	O
+isomer	O
+.	O
+
+CD7	B-GENE
++	O
+/	O
+CD3	B-GENE
+-	O
+T	O
+-	O
+cell	O
+precursors	O
+exhibit	O
+V	B-GENE
+delta	I-GENE
+2D	I-GENE
+delta	I-GENE
+3	I-GENE
+rearrangements	I-GENE
+.	O
+
+HVH2	B-GENE
+mRNA	I-GENE
+showed	O
+an	O
+expression	O
+pattern	O
+distinct	O
+from	O
+CL100	B-GENE
+(	O
+human	B-GENE
+homologue	I-GENE
+of	I-GENE
+mouse	I-GENE
+MKP1	I-GENE
+)	O
+and	O
+PAC1	B-GENE
+,	O
+two	O
+previously	O
+identified	O
+MAP	B-GENE
+kinase	I-GENE
+phosphatases	I-GENE
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+these	O
+sequences	O
+located	O
+immediately	O
+3	O
+'	O
+to	O
+the	O
+breakpoint	O
+of	O
+the	O
+HPFH	B-GENE
+-	I-GENE
+3	I-GENE
+deletion	I-GENE
+,	O
+exhibit	O
+both	O
+the	O
+structure	O
+and	O
+the	O
+function	O
+of	O
+an	O
+enhancer	O
+,	O
+and	O
+can	O
+modify	O
+the	O
+developmental	O
+specificity	O
+of	O
+the	O
+fetal	B-GENE
+gamma	I-GENE
+-	I-GENE
+globin	I-GENE
+genes	I-GENE
+,	O
+resulting	O
+in	O
+their	O
+continued	O
+expression	O
+during	O
+adult	O
+life	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+interaction	O
+between	O
+Jak2	B-GENE
+and	O
+PRLR	B-GENE
+requires	O
+a	O
+proline	O
+-	O
+rich	O
+sequence	O
+in	O
+the	O
+membrane	O
+proximal	O
+region	O
+of	O
+the	O
+receptor	O
+,	O
+which	O
+is	O
+conserved	O
+among	O
+the	O
+different	O
+members	O
+of	O
+the	O
+cytokine	B-GENE
+receptor	I-GENE
+superfamily	I-GENE
+.	O
+
+Transcription	O
+of	O
+the	O
+vascular	B-GENE
+cell	I-GENE
+adhesion	I-GENE
+molecule	I-GENE
+1	I-GENE
+(	O
+VCAM	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+gene	O
+in	O
+endothelial	O
+cells	O
+is	O
+induced	O
+by	O
+lipopolysaccharide	O
+and	O
+the	O
+inflammatory	O
+cytokines	B-GENE
+interleukin	I-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+and	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+.	O
+
+Experiments	O
+with	O
+recombinant	O
+proteins	O
+showed	O
+that	O
+p50	B-GENE
+/	O
+p65	B-GENE
+and	O
+high	B-GENE
+-	I-GENE
+mobility	I-GENE
+-	I-GENE
+group	I-GENE
+I	I-GENE
+(	I-GENE
+Y	I-GENE
+)	I-GENE
+protein	I-GENE
+cooperatively	O
+facilitated	O
+the	O
+binding	O
+of	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+to	O
+the	O
+VCAM1	B-GENE
+IRF	B-GENE
+binding	I-GENE
+site	I-GENE
+and	O
+that	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+physically	O
+interacted	O
+with	O
+p50	B-GENE
+and	O
+with	O
+high	B-GENE
+-	I-GENE
+mobility	I-GENE
+-	I-GENE
+group	I-GENE
+I	I-GENE
+(	I-GENE
+Y	I-GENE
+)	I-GENE
+protein	I-GENE
+.	O
+
+Based	O
+on	O
+these	O
+results	O
+the	O
+minimal	O
+control	O
+element	O
+(	O
+AX	O
+470	O
+)	O
+specifying	O
+the	O
+anterior	O
+boundary	O
+of	O
+Hox	B-GENE
+expression	O
+was	O
+designated	O
+as	O
+Hoxa	B-GENE
+-	I-GENE
+7	I-GENE
+enhancer	I-GENE
+.	O
+
+In	O
+this	O
+report	O
+we	O
+describe	O
+the	O
+isolation	O
+of	O
+a	O
+Fab	B-GENE
+fragment	I-GENE
+(	O
+Fab	B-GENE
+A8	I-GENE
+)	O
+showing	O
+a	O
+high	O
+relative	O
+affinity	O
+for	O
+the	O
+receptor	O
+(	O
+0	O
+.	O
+5	O
+nM	O
+)	O
+.	O
+
+MBP	B-GENE
+-	O
+Rep68	B-GENE
+delta	I-GENE
+-	O
+mediated	O
+DNA	O
+-	O
+RNA	O
+helicase	O
+activity	O
+required	O
+ATP	O
+hydrolysis	O
+and	O
+the	O
+presence	O
+of	O
+Mg2	O
++	O
+ions	O
+and	O
+was	O
+inhibited	O
+by	O
+high	O
+ionic	O
+strength	O
+.	O
+
+To	O
+identify	O
+critical	O
+regions	O
+mediating	O
+growth	O
+signal	O
+transduction	O
+by	O
+hG	B-GENE
+-	I-GENE
+CSFR	I-GENE
+,	O
+deletions	O
+or	O
+site	O
+-	O
+directed	O
+amino	O
+acid	O
+substitutions	O
+were	O
+introduced	O
+into	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+hG	B-GENE
+-	I-GENE
+CSFR	I-GENE
+,	O
+and	O
+the	O
+mutant	O
+cDNAs	O
+were	O
+transfected	O
+into	O
+the	O
+murine	B-GENE
+interleukin	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+-	O
+dependent	O
+Ba	O
+/	O
+F3	O
+and	O
+FDCP	O
+cell	O
+lines	O
+.	O
+
+When	O
+combined	O
+with	O
+independent	O
+activating	O
+mutations	O
+in	O
+the	O
+c	B-GENE
+-	I-GENE
+abl	I-GENE
+kinase	I-GENE
+domain	I-GENE
+or	O
+NH2	O
+-	O
+terminus	O
+,	O
+the	O
+G128R	B-GENE
+mutation	O
+blocked	O
+transformation	O
+by	O
+the	O
+double	O
+mutant	O
+,	O
+suggesting	O
+that	O
+the	O
+G128R	B-GENE
+mutant	I-GENE
+was	O
+unable	O
+to	O
+transform	O
+cells	O
+for	O
+trivial	O
+reasons	O
+.	O
+
+Both	O
+mutations	O
+completely	O
+abolished	O
+binding	O
+of	O
+the	O
+Abl	B-GENE
+SH3	B-GENE
+domain	O
+to	O
+proline	O
+-	O
+rich	O
+target	O
+proteins	O
+in	O
+a	O
+filter	O
+-	O
+binding	O
+assay	O
+.	O
+
+Changes	O
+induced	O
+in	O
+the	O
+gills	O
+of	O
+milkfish	O
+(	O
+Chanos	O
+chanos	O
+Forsskal	O
+)	O
+fingerlings	O
+after	O
+acute	O
+exposure	O
+to	O
+nifurpirinol	O
+(	O
+Furanace	O
+;	O
+P	O
+-	O
+7138	O
+)	O
+.	O
+
+Retreatment	O
+of	O
+these	O
+2	O
+dogs	O
+resulted	O
+in	O
+a	O
+similar	O
+,	O
+but	O
+blunted	O
+,	O
+response	O
+to	O
+human	B-GENE
+immunoglobulin	I-GENE
+.	O
+
+The	O
+levels	O
+of	O
+NSE	B-GENE
+and	O
+MBP	B-GENE
+in	O
+the	O
+IJVB	O
+were	O
+compared	O
+to	O
+those	O
+in	O
+the	O
+PVB	O
+.	O
+
+Morphologic	O
+variables	O
+included	O
+cancer	O
+volume	O
+,	O
+histologic	O
+grade	O
+,	O
+capsular	O
+penetration	O
+,	O
+seminal	O
+vesicle	O
+invasion	O
+,	O
+and	O
+lymph	O
+node	O
+metastasis	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+these	O
+regions	O
+showed	O
+a	O
+CAAT	O
+box	O
+upstream	O
+of	O
+exon	O
+1a	O
+and	O
+high	O
+G	O
+-	O
+C	O
+content	O
+regions	O
+within	O
+both	O
+P1	O
+and	O
+P2	O
+.	O
+
+The	O
+fusion	O
+proteins	O
+were	O
+tested	O
+by	O
+ELISA	O
+for	O
+reactivity	O
+with	O
+a	O
+panel	O
+of	O
+human	B-GENE
+anti	I-GENE
+-	I-GENE
+La	I-GENE
+sera	I-GENE
+in	O
+order	O
+to	O
+define	O
+the	O
+nature	O
+of	O
+the	O
+epitopes	O
+.	O
+
+GCD10	B-GENE
+was	O
+first	O
+identified	O
+genetically	O
+as	O
+a	O
+translational	O
+repressor	O
+of	O
+GCN4	B-GENE
+.	O
+
+GCD10	B-GENE
+binds	O
+RNA	O
+in	O
+vitro	O
+and	O
+we	O
+present	O
+strong	O
+biochemical	O
+evidence	O
+that	O
+it	O
+is	O
+identical	O
+to	O
+the	O
+RNA	O
+-	O
+binding	O
+subunit	O
+of	O
+yeast	B-GENE
+initiation	I-GENE
+factor	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+eIF	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+.	O
+eIF	B-GENE
+-	I-GENE
+3	I-GENE
+is	O
+a	O
+multisubunit	O
+complex	O
+that	O
+stimulates	O
+translation	O
+initiation	O
+in	O
+vitro	O
+at	O
+several	O
+different	O
+steps	O
+.	O
+
+Sources	O
+of	O
+noise	O
+in	O
+these	O
+signals	O
+were	O
+evaluated	O
+in	O
+preparations	O
+stained	O
+with	O
+the	O
+potentiometric	O
+probe	O
+RH	O
+-	O
+414	O
+.	O
+
+1993	O
+.	O
+
+A	O
+transformation	O
+-	O
+competent	O
+mutant	O
+,	O
+like	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+E5	I-GENE
+protein	I-GENE
+,	O
+bound	O
+the	O
+receptor	O
+and	O
+induced	O
+receptor	O
+tyrosine	O
+phosphorylation	O
+and	O
+down	O
+-	O
+regulation	O
+.	O
+
+We	O
+conclude	O
+that	O
+cAMP	O
+,	O
+acting	O
+through	O
+PKA	B-GENE
+,	O
+is	O
+an	O
+essential	O
+regulator	O
+of	O
+basal	O
+CFTR	B-GENE
+gene	I-GENE
+expression	O
+and	O
+may	O
+mediate	O
+an	O
+induction	O
+of	O
+CFTR	B-GENE
+in	O
+responsive	O
+cell	O
+types	O
+.	O
+
+Both	O
+PPC	O
+-	O
+1	O
+and	O
+ALVA	O
+-	O
+31	O
+cells	O
+display	O
+tumorigenesis	O
+and	O
+invasiveness	O
+in	O
+nude	O
+mice	O
+,	O
+whereas	O
+LNCap	O
+cells	O
+exhibit	O
+a	O
+less	O
+malignant	O
+phenotype	O
+,	O
+suggesting	O
+a	O
+correlation	O
+between	O
+CD44	B-GENE
+variant	I-GENE
+(	O
+CD44v	B-GENE
+)	O
+expression	O
+and	O
+aggressive	O
+prostate	O
+tumor	O
+behavior	O
+.	O
+
+Two	O
+such	O
+genes	O
+,	O
+designated	O
+hsiggll150	B-GENE
+and	O
+hsiggll295	B-GENE
+,	O
+were	O
+cloned	O
+and	O
+sequenced	O
+from	O
+genomic	O
+DNA	O
+.	O
+
+A	O
+retrospective	O
+epidemiological	O
+study	O
+is	O
+reported	O
+concerning	O
+burn	O
+injuries	O
+in	O
+775	O
+children	O
+hospitalized	O
+at	O
+the	O
+unit	O
+of	O
+burn	O
+care	O
+of	O
+Casablanca	O
+between	O
+1985	O
+and	O
+1993	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+protein	O
+binding	O
+to	O
+the	O
+E2F	B-GENE
+-	I-GENE
+like	I-GENE
+sequences	I-GENE
+may	O
+act	O
+to	O
+reduce	O
+expression	O
+.	O
+
+The	O
+RAD6	B-GENE
+/	O
+UBC2	B-GENE
+gene	O
+from	O
+Saccharomyces	O
+cerevisiae	O
+encodes	O
+a	O
+ubiquitin	B-GENE
+-	I-GENE
+conjugating	I-GENE
+enzyme	I-GENE
+involved	O
+in	O
+DNA	O
+repair	O
+,	O
+induced	O
+mutagenesis	O
+,	O
+and	O
+sporulation	O
+.	O
+
+Echocardiography	O
+revealed	O
+right	O
+ventricular	O
+diastolic	O
+collapse	O
+(	O
+RVDC	O
+)	O
+without	O
+physical	O
+signs	O
+of	O
+cardiac	O
+tamponade	O
+.	O
+
+In	O
+on	O
+-	O
+going	O
+screening	O
+programmes	O
+,	O
+the	O
+Haemoccult	O
+test	O
+consists	O
+of	O
+six	O
+slides	O
+and	O
+a	O
+test	O
+is	O
+considered	O
+positive	O
+if	O
+at	O
+least	O
+one	O
+slide	O
+is	O
+coloured	O
+.	O
+
+We	O
+showed	O
+previously	O
+that	O
+a	O
+fusion	O
+protein	O
+(	O
+GAL4	B-GENE
+-	O
+p40	B-GENE
+)	O
+containing	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+GAL4	B-GENE
+and	O
+sequences	O
+of	O
+chicken	B-GENE
+l	I-GENE
+kappa	I-GENE
+B	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+p40	B-GENE
+)	O
+inhibits	O
+growth	O
+in	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+We	O
+have	O
+demonstrated	O
+previously	O
+that	O
+two	O
+binding	O
+sites	O
+in	O
+the	O
+-	B-GENE
+184	I-GENE
+HNF	I-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+promoter	I-GENE
+are	O
+recognized	O
+by	O
+widely	O
+distributed	O
+factors	O
+and	O
+that	O
+there	O
+is	O
+also	O
+a	O
+critical	O
+autoregulatory	O
+site	O
+,	O
+we	O
+identified	O
+a	O
+binding	O
+site	O
+for	O
+a	O
+cell	O
+-	O
+specific	O
+factor	O
+,	O
+LF	B-GENE
+-	I-GENE
+H3	I-GENE
+beta	I-GENE
+,	O
+that	O
+may	O
+function	O
+in	O
+restricting	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+gene	I-GENE
+expression	O
+to	O
+hepatocytes	O
+.	O
+
+In	O
+4	O
+spinalized	O
+cats	O
+,	O
+the	O
+effects	O
+of	O
+afferent	O
+inputs	O
+from	O
+hindlimb	O
+cutaneous	O
+nerves	O
+(	O
+sural	O
+cutaneous	O
+nerve	O
+:	O
+Sur	O
+)	O
+on	O
+mono	O
+-	O
+and	O
+poly	O
+-	O
+synaptic	O
+reflex	O
+recorded	O
+from	O
+tail	O
+muscle	O
+motoneurons	O
+were	O
+studied	O
+before	O
+and	O
+after	O
+spinal	O
+lesioning	O
+at	O
+S2	O
+-	O
+3	O
+level	O
+.	O
+
+The	O
+flow	O
+rate	O
+of	O
+phosphate	O
+buffered	O
+saline	O
+through	O
+dermis	O
+was	O
+measured	O
+as	O
+a	O
+function	O
+of	O
+applied	O
+pressure	O
+.	O
+
+However	O
+,	O
+parallax	O
+measurements	O
+showed	O
+that	O
+at	O
+150K	O
+,	O
+collapse	O
+of	O
+Epon	O
+sections	O
+does	O
+not	O
+take	O
+place	O
+.	O
+
+Although	O
+within	O
+normal	O
+limits	O
+,	O
+latency	O
+was	O
+high	O
+.	O
+
+The	O
+outcome	O
+of	O
+the	O
+optimization	O
+of	O
+the	O
+seven	O
+-	O
+field	O
+plan	O
+prompted	O
+an	O
+investigation	O
+into	O
+the	O
+best	O
+results	O
+that	O
+could	O
+be	O
+achieved	O
+by	O
+an	O
+"	O
+ideal	O
+"	O
+conformal	O
+radiotherapy	O
+technique	O
+.	O
+
+Specific	O
+requirements	O
+for	O
+branched	O
+-	O
+chain	O
+amino	O
+acids	O
+,	O
+glutamine	O
+,	O
+and	O
+arginine	O
+are	O
+evaluated	O
+.	O
+
+The	O
+pea	B-GENE
+rps10	I-GENE
+intron	I-GENE
+is	O
+homologous	O
+to	O
+introns	O
+in	O
+rrn26	B-GENE
+and	O
+cox3	B-GENE
+in	O
+the	O
+Marchantia	O
+mitochondrial	O
+genome	O
+,	O
+while	O
+the	O
+Marchantia	B-GENE
+rps10	I-GENE
+gene	I-GENE
+lacks	O
+an	O
+intron	O
+.	O
+
+Serum	O
+magnesium	O
+in	O
+79	O
+patients	O
+of	O
+gynecologic	O
+neoplasms	O
+treated	O
+with	O
+cisplatin	O
+and	O
+their	O
+controls	O
+was	O
+measured	O
+.	O
+
+Alanine	B-GENE
+aminotransferase	I-GENE
+(	O
+ALT	B-GENE
+)	O
+levels	O
+had	O
+been	O
+elevated	O
+for	O
+six	O
+months	O
+in	O
+all	O
+patients	O
+and	O
+hepatitis	O
+B	O
+viral	O
+infection	O
+was	O
+replicative	O
+.	O
+
+In	O
+this	O
+study	O
+we	O
+have	O
+investigated	O
+the	O
+role	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+in	O
+initiating	O
+the	O
+adipogenic	O
+program	O
+by	O
+overexpressing	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+in	O
+multipotential	O
+NIH	O
+-	O
+3T3	O
+fibroblasts	O
+.	O
+
+XYL1	B-GENE
+was	O
+isolated	O
+as	O
+a	O
+highly	O
+expressed	O
+fusion	O
+clone	O
+from	O
+a	O
+'	B-GENE
+lacZ	I-GENE
+translational	O
+fusion	O
+library	O
+.	O
+
+Various	O
+transcripts	O
+are	O
+generated	O
+from	O
+the	O
+VCSA1	B-GENE
+gene	I-GENE
+by	O
+alternative	O
+splicing	O
+and	O
+poly	O
+(	O
+A	O
+)	O
+processing	O
+in	O
+the	O
+rat	O
+submandibular	O
+gland	O
+.	O
+
+However	O
+,	O
+division	O
+of	O
+the	O
+chest	O
+wall	O
+muscles	O
+,	O
+usually	O
+with	O
+diathermy	O
+,	O
+contributes	O
+to	O
+prolonged	O
+pain	O
+and	O
+morbidity	O
+.	O
+
+Closure	O
+of	O
+an	O
+open	O
+high	O
+below	O
+-	O
+knee	O
+guillotine	O
+amputation	O
+wound	O
+using	O
+a	O
+skin	O
+-	O
+stretching	O
+device	O
+.	O
+
+Our	O
+study	O
+was	O
+addressed	O
+to	O
+the	O
+synthesis	O
+of	O
+some	O
+derivatives	O
+of	O
+this	O
+sequence	O
+in	O
+order	O
+to	O
+obtain	O
+both	O
+peptide	O
+substrates	O
+suitable	O
+for	O
+the	O
+detection	O
+of	O
+the	O
+Src	B-GENE
+-	O
+like	O
+tyrosine	B-GENE
+kinase	I-GENE
+activity	O
+and	O
+active	O
+site	O
+-	O
+directed	O
+inhibitors	O
+specific	O
+for	O
+this	O
+class	O
+of	O
+enzymes	O
+.	O
+
+Citrate	B-GENE
+synthase	I-GENE
+activity	O
+was	O
+increased	O
+in	O
+the	O
+medial	O
+head	O
+(	O
+81	O
+%	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+the	O
+red	O
+long	O
+head	O
+(	O
+88	O
+%	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+of	O
+the	O
+triceps	O
+brachii	O
+muscle	O
+in	O
+R	O
+rats	O
+but	O
+not	O
+in	O
+the	O
+white	O
+long	O
+head	O
+(	O
+25	O
+%	O
+,	O
+P	O
+=	O
+0	O
+.	O
+06	O
+)	O
+.	O
+
+The	O
+expression	O
+of	O
+the	O
+putative	O
+operon	O
+bglPH	B-GENE
+of	O
+Bacillus	O
+subtilis	O
+was	O
+studied	O
+by	O
+using	O
+bglP	B-GENE
+'	I-GENE
+-	O
+lacZ	B-GENE
+transcriptional	O
+fusions	O
+.	O
+
+Although	O
+eight	O
+contiguous	O
+genes	O
+necessary	O
+for	O
+urease	B-GENE
+activity	O
+have	O
+been	O
+cloned	O
+and	O
+sequenced	O
+,	O
+the	O
+transcriptional	O
+organization	O
+and	O
+regulation	O
+of	O
+specific	O
+genes	O
+within	O
+the	O
+Proteus	B-GENE
+gene	I-GENE
+cluster	I-GENE
+has	O
+not	O
+been	O
+investigated	O
+in	O
+detail	O
+.	O
+
+The	O
+hypBFCDE	B-GENE
+operon	I-GENE
+from	O
+Rhizobium	O
+leguminosarum	O
+biovar	O
+viciae	O
+is	O
+expressed	O
+from	O
+an	O
+Fnr	B-GENE
+-	I-GENE
+type	I-GENE
+promoter	I-GENE
+that	O
+escapes	O
+mutagenesis	O
+of	O
+the	O
+fnrN	B-GENE
+gene	I-GENE
+.	O
+
+We	O
+demonstrate	O
+that	O
+a	O
+VT	O
++	O
+peptide	O
+was	O
+specifically	O
+phosphorylated	O
+by	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+(	O
+PKC	B-GENE
+)	O
+in	O
+vitro	O
+,	O
+but	O
+not	O
+by	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+(	O
+PKA	B-GENE
+)	O
+.	O
+
+R	O
+.	O
+
+15	O
+,	O
+2500	O
+-	O
+2508	O
+;	O
+O	O
+'	O
+Neill	O
+,	O
+T	O
+.	O
+
+Control	O
+experiments	O
+showed	O
+that	O
+each	O
+fusion	O
+protein	O
+had	O
+a	O
+high	O
+affinity	O
+binding	O
+site	O
+for	O
+estradiol	O
+-	O
+17	O
+beta	O
+and	O
+could	O
+transactivate	O
+an	O
+ERE	O
+-	O
+LacZ	B-GENE
+reporter	O
+gene	O
+in	O
+yeast	O
+similar	O
+to	O
+the	O
+wild	B-GENE
+type	I-GENE
+ER	I-GENE
+.	O
+
+Although	O
+Micrococcus	B-GENE
+luteus	I-GENE
+UV	I-GENE
+endonuclease	I-GENE
+has	O
+been	O
+reported	O
+to	O
+be	O
+an	O
+18	O
+-	O
+kDa	O
+enzyme	O
+with	O
+possible	O
+homology	O
+to	O
+the	O
+16	B-GENE
+-	I-GENE
+kDa	I-GENE
+endonuclease	I-GENE
+V	I-GENE
+from	I-GENE
+bacteriophage	I-GENE
+T4	I-GENE
+(	O
+Gordon	O
+,	O
+L	O
+.	O
+
+Several	O
+different	O
+oncogenes	O
+and	O
+growth	O
+factors	O
+promote	O
+G1	O
+phase	O
+progression	O
+.	O
+
+Cyclin	B-GENE
+D1	I-GENE
+promoter	I-GENE
+activity	O
+was	O
+stimulated	O
+by	O
+overexpression	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+p41MAPK	B-GENE
+)	O
+or	O
+c	B-GENE
+-	I-GENE
+Ets	I-GENE
+-	I-GENE
+2	I-GENE
+through	O
+the	O
+proximal	O
+22	O
+base	O
+pairs	O
+.	O
+
+Indeed	O
+,	O
+ERM	B-GENE
+and	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+synergistically	O
+activated	O
+the	O
+EBS	O
+-	O
+CRE	O
+without	O
+making	O
+an	O
+apparent	O
+ternary	O
+complex	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+R206S	B-GENE
+HSF	I-GENE
+substitution	O
+exhibits	O
+constitutive	O
+transcriptional	O
+activation	O
+from	O
+a	O
+consensus	O
+HSE	O
+(	O
+HSE2	O
+)	O
+.	O
+
+After	O
+recovery	O
+,	O
+a	O
+hypertonic	O
+saline	O
+challenge	O
+was	O
+performed	O
+.	O
+
+The	O
+range	O
+of	O
+eosinophils	O
+was	O
+22	O
+-	O
+56	O
+%	O
+of	O
+the	O
+number	O
+of	O
+peripheral	O
+white	O
+blood	O
+cells	O
+(	O
+mean	O
+nadir	O
+33	O
+%	O
+)	O
+.	O
+
+Comparisons	O
+of	O
+rrnB	B-GENE
+P1	B-GENE
+-	O
+lacZ	B-GENE
+expression	O
+at	O
+different	O
+ppGpp	O
+levels	O
+is	O
+interpreted	O
+for	O
+the	O
+rpoD	B-GENE
+(	I-GENE
+P504L	I-GENE
+)	I-GENE
+mutant	I-GENE
+as	O
+resulting	O
+from	O
+a	O
+hypersensitivity	O
+to	O
+ppGpp	O
+.	O
+
+These	O
+intron	O
+chimeras	O
+show	O
+that	O
+peripheral	O
+sequences	O
+and	O
+the	O
+elements	O
+that	O
+define	O
+the	O
+splice	O
+sites	O
+are	O
+adequate	O
+for	O
+self	O
+-	O
+splicing	O
+activity	O
+but	O
+that	O
+the	O
+central	O
+portions	O
+containing	O
+the	O
+catalytic	O
+cores	O
+of	O
+ai4	B-GENE
+and	O
+bi4	B-GENE
+are	O
+deficient	O
+;	O
+these	O
+cores	O
+are	O
+the	O
+likely	O
+targets	O
+of	O
+the	O
+splicing	O
+proteins	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+genetically	O
+that	O
+plus	O
+-	O
+strand	O
+DNA	O
+synthesis	O
+of	O
+the	O
+yeast	B-GENE
+Ty1	I-GENE
+element	I-GENE
+is	O
+initiated	O
+at	O
+two	O
+sites	O
+located	O
+at	O
+the	O
+5	O
+'	O
+boundary	O
+of	O
+the	O
+3	O
+'	O
+long	O
+terminal	O
+repeat	O
+(	O
+PPT1	B-GENE
+)	O
+and	O
+near	O
+the	O
+middle	O
+of	O
+the	O
+pol	B-GENE
+gene	I-GENE
+in	O
+the	O
+integrase	B-GENE
+coding	I-GENE
+sequence	I-GENE
+(	O
+PPT2	B-GENE
+)	O
+.	O
+
+Characterization	O
+of	O
+the	O
+3	O
+'	O
+ends	O
+of	O
+the	O
+plus	O
+-	O
+strand	O
+DNA	O
+fragments	O
+reveals	O
+(	O
+1	O
+)	O
+that	O
+the	O
+upstream	O
+fragment	O
+is	O
+elongated	O
+beyond	O
+PPT2	B-GENE
+creating	O
+a	O
+plus	O
+-	O
+strand	O
+overlap	O
+and	O
+(	O
+2	O
+)	O
+that	O
+the	O
+majority	O
+of	O
+plus	O
+-	O
+strand	O
+strong	O
+-	O
+stop	O
+DNA	O
+fragments	O
+bear	O
+a	O
+copy	O
+of	O
+the	O
+minus	O
+-	O
+strand	O
+primer	O
+binding	O
+site	O
+in	O
+agreement	O
+with	O
+the	O
+accepted	O
+model	O
+of	O
+retroviral	O
+genomic	O
+RNA	O
+reverse	O
+transcription	O
+.	O
+
+The	O
+patients	O
+undergoing	O
+VTLB	O
+had	O
+significantly	O
+shorter	O
+operative	O
+times	O
+(	O
+VTLB	O
+,	O
+100	O
+.	O
+2	O
++	O
+/	O
+-	O
+27	O
+.	O
+2	O
+min	O
+.	O
+vs	O
+OLB	O
+,	O
+119	O
+.	O
+8	O
++	O
+/	O
+-	O
+42	O
+.	O
+6	O
+min	O
+;	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+and	O
+less	O
+blood	O
+loss	O
+(	O
+VTLB	O
+,	O
+4	O
+.	O
+7	O
++	O
+/	O
+-	O
+14	O
+.	O
+6	O
+ml	O
+vs	O
+OLB	O
+,	O
+65	O
+.	O
+7	O
++	O
+/	O
+-	O
+77	O
+.	O
+0	O
+ml	O
+;	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+By	O
+150	O
+minutes	O
+after	O
+Cr2O3	O
+inhalation	O
+,	O
+FEV1	O
+.	O
+0	O
+had	O
+decreased	O
+by	O
+32	O
+%	O
+.	O
+
+This	O
+combined	O
+intravenous	O
+anaesthetic	O
+regimen	O
+gave	O
+good	O
+anaesthesia	O
+and	O
+analgesia	O
+to	O
+pigs	O
+for	O
+up	O
+to	O
+2	O
+h	O
+as	O
+monitored	O
+by	O
+clinical	O
+signs	O
+.	O
+
+Twenty	O
+food	O
+products	O
+were	O
+contaminated	O
+with	O
+V	O
+.	O
+cholerae	O
+O1	O
+,	O
+Ogawa	O
+,	O
+toxigenic	O
+and	O
+not	O
+toxigenic	O
+strains	O
+:	O
+yoghurt	O
+,	O
+cream	O
+cheese	O
+,	O
+apricot	O
+marmelade	O
+,	O
+hip	O
+rose	O
+marmelade	O
+,	O
+mayonnaise	O
+,	O
+italian	O
+pasta	O
+for	O
+"	O
+empanadas	O
+"	O
+,	O
+"	O
+dulce	O
+de	O
+leche	O
+"	O
+,	O
+meat	O
+sausage	O
+,	O
+meat	O
+and	O
+spinach	O
+ravioli	O
+,	O
+margarine	O
+,	O
+milk	O
+dessert	O
+(	O
+made	O
+with	O
+cocoa	O
+,	O
+milk	O
+confiture	O
+,	O
+starch	O
+and	O
+additives	O
+)	O
+,	O
+lettuce	O
+,	O
+tuna	O
+fish	O
+,	O
+ricotta	O
+and	O
+sterilized	O
+milk	O
+.	O
+
+It	O
+is	O
+impossible	O
+to	O
+define	O
+only	O
+one	O
+clinical	O
+outline	O
+because	O
+both	O
+symptomatic	O
+and	O
+asymptomatic	O
+infected	O
+NB	O
+may	O
+be	O
+found	O
+with	O
+gestational	O
+age	O
+at	O
+term	O
+and	O
+pre	O
+-	O
+term	O
+and	O
+when	O
+born	O
+with	O
+a	O
+weight	O
+above	O
+or	O
+below	O
+2000	O
+g	O
+.	O
+
+The	O
+expression	O
+of	O
+the	O
+pilin	B-GENE
+gene	I-GENE
+,	O
+tcpA	B-GENE
+,	O
+is	O
+dependent	O
+upon	O
+ToxR	B-GENE
+and	O
+upon	O
+ToxT	B-GENE
+.	O
+
+Ras	B-GENE
+p21Val	I-GENE
+inhibits	O
+myogenesis	O
+without	O
+altering	O
+the	O
+DNA	O
+binding	O
+or	O
+transcriptional	O
+activities	O
+of	O
+the	O
+myogenic	B-GENE
+basic	I-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+factors	I-GENE
+.	O
+
+In	O
+cells	O
+limited	O
+for	O
+His	O
+,	O
+increased	O
+expression	O
+of	O
+arg	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+cpc	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+decreased	O
+expression	O
+of	O
+cox	B-GENE
+-	I-GENE
+5	I-GENE
+,	O
+also	O
+had	O
+translational	O
+and	O
+transcriptional	O
+components	O
+.	O
+
+The	O
+peptide	O
+sequences	O
+reveal	O
+that	O
+the	O
+factor	O
+consists	O
+of	O
+GABP	B-GENE
+alpha	I-GENE
+and	O
+GABP	B-GENE
+beta	I-GENE
+1	I-GENE
+with	O
+Ets	B-GENE
+and	O
+Notch	B-GENE
+motifs	I-GENE
+,	O
+respectively	O
+.	O
+
+Immunofluorescence	O
+microscopy	O
+and	O
+cell	O
+fractionation	O
+analyses	O
+showed	O
+that	O
+the	O
+110	O
+-	O
+kDa	O
+protein	O
+was	O
+exclusively	O
+nuclear	O
+,	O
+whereas	O
+the	O
+150	O
+-	O
+kDa	O
+protein	O
+was	O
+present	O
+in	O
+both	O
+the	O
+cytoplasm	O
+and	O
+nucleus	O
+of	O
+human	O
+cells	O
+.	O
+
+Expression	O
+and	O
+regulation	O
+by	O
+interferon	B-GENE
+of	O
+a	O
+double	B-GENE
+-	I-GENE
+stranded	I-GENE
+-	I-GENE
+RNA	I-GENE
+-	I-GENE
+specific	I-GENE
+adenosine	I-GENE
+deaminase	I-GENE
+from	O
+human	O
+cells	O
+:	O
+evidence	O
+for	O
+two	O
+forms	O
+of	O
+the	O
+deaminase	O
+.	O
+
+T	O
+-	O
+cell	O
+hybridomas	O
+,	O
+thymocytes	O
+,	O
+and	O
+T	O
+cells	O
+can	O
+be	O
+induced	O
+to	O
+undergo	O
+apoptotic	O
+cell	O
+death	O
+by	O
+activation	O
+through	O
+the	O
+T	B-GENE
+-	I-GENE
+cell	I-GENE
+receptor	I-GENE
+.	O
+
+Deletions	O
+were	O
+examined	O
+in	O
+the	O
+LYS2	B-GENE
+gene	I-GENE
+,	O
+using	O
+a	O
+set	O
+of	O
+31	O
+-	O
+to	O
+156	O
+-	O
+bp	O
+inserts	O
+that	O
+included	O
+inserts	O
+with	O
+no	O
+apparent	O
+potential	O
+for	O
+secondary	O
+structure	O
+as	O
+well	O
+as	O
+two	O
+quasipalindromes	O
+.	O
+
+Overexpression	O
+of	O
+SCS1	B-GENE
+could	O
+not	O
+complement	O
+an	O
+HSP60	B-GENE
+-	I-GENE
+null	I-GENE
+allele	I-GENE
+,	O
+indicating	O
+that	O
+suppression	O
+was	O
+not	O
+due	O
+to	O
+the	O
+bypassing	O
+of	O
+Hsp60	B-GENE
+activity	O
+.	O
+
+The	O
+DNA	O
+binding	O
+domain	O
+of	O
+NirA	B-GENE
+was	O
+expressed	O
+as	O
+a	O
+fusion	O
+protein	O
+with	O
+the	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+of	O
+Schistosoma	O
+japonicum	O
+.	O
+
+The	O
+kinase	O
+is	O
+essential	O
+in	O
+vivo	O
+for	O
+normal	O
+phosphorylation	O
+of	O
+the	O
+CTD	O
+and	O
+for	O
+normal	O
+growth	O
+and	O
+differentiation	O
+.	O
+
+Finally	O
+,	O
+we	O
+demonstrate	O
+that	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+alpha	I-GENE
+can	O
+also	O
+active	O
+the	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+promoter	O
+in	O
+nonmyeloid	O
+cells	O
+.	O
+
+Endocytosis	O
+and	O
+vacuolar	O
+degradation	O
+of	O
+the	O
+plasma	O
+membrane	O
+-	O
+localized	O
+Pdr5	B-GENE
+ATP	I-GENE
+-	I-GENE
+binding	I-GENE
+cassette	I-GENE
+multidrug	I-GENE
+transporter	I-GENE
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Disruption	O
+of	O
+the	O
+HOG1	B-GENE
+and	O
+PBS2	B-GENE
+genes	I-GENE
+leads	O
+to	O
+a	O
+dramatic	O
+decrease	O
+of	O
+the	O
+HSP12	B-GENE
+inducibility	O
+in	O
+osmostressed	O
+cells	O
+,	O
+whereas	O
+overproduction	O
+of	O
+Hog1	B-GENE
+produces	O
+a	O
+fivefold	O
+increase	O
+in	O
+wild	O
+-	O
+type	O
+induced	O
+levels	O
+upon	O
+a	O
+shift	O
+to	O
+a	O
+high	O
+salt	O
+concentration	O
+.	O
+
+Deletion	O
+or	O
+inactivation	O
+of	O
+CRY1	B-GENE
+leads	O
+to	O
+5	O
+-	O
+to	O
+10	O
+-	O
+fold	O
+-	O
+increased	O
+levels	O
+of	O
+CRY2	B-GENE
+mRNA	I-GENE
+.	O
+
+(	O
+1986	O
+)	O
+method	O
+of	O
+separation	O
+of	O
+Cryptosporidium	O
+spp	O
+.	O
+oocysts	O
+from	O
+feces	O
+by	O
+using	O
+a	O
+percoll	O
+discontinuous	O
+density	O
+gradient	O
+appeared	O
+a	O
+method	O
+of	O
+choice	O
+for	O
+obtaining	O
+large	O
+numbers	O
+of	O
+oocysts	O
+of	O
+C	O
+.	O
+parvum	O
+free	O
+of	O
+fecal	O
+contamination	O
+.	O
+
+METHODS	O
+:	O
+We	O
+obtained	O
+maximal	O
+inspiratory	O
+and	O
+expiratory	O
+flow	O
+-	O
+volume	O
+curves	O
+in	O
+41	O
+unselected	O
+patients	O
+with	O
+essential	O
+tremor	O
+(	O
+14	O
+males	O
+,	O
+27	O
+females	O
+,	O
+age	O
+61	O
+.	O
+7	O
++	O
+/	O
+-	O
+2	O
+.	O
+14	O
+years	O
+)	O
+.	O
+
+Our	O
+findings	O
+also	O
+provide	O
+the	O
+basis	O
+for	O
+the	O
+development	O
+of	O
+assays	O
+to	O
+screen	O
+for	O
+the	O
+ligands	O
+to	O
+testis	B-GENE
+receptor	I-GENE
+2	I-GENE
+and	O
+hERR1	B-GENE
+.	O
+
+Four	O
+p53	B-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+domain	I-GENE
+peptides	I-GENE
+bind	O
+natural	O
+p53	B-GENE
+-	I-GENE
+response	I-GENE
+elements	I-GENE
+and	O
+bend	O
+the	O
+DNA	O
+.	O
+
+The	O
+Stat5b	B-GENE
+mRNA	I-GENE
+has	O
+a	O
+size	O
+of	O
+5	O
+.	O
+6	O
+kb	O
+and	O
+encodes	O
+a	O
+protein	O
+of	O
+786	O
+amino	O
+acids	O
+.	O
+
+The	O
+hydropathy	O
+plot	O
+revealed	O
+a	O
+rather	O
+hydrophilic	O
+N	O
+-	O
+terminal	O
+region	O
+and	O
+the	O
+absence	O
+of	O
+a	O
+hydrophobic	O
+signal	O
+peptide	O
+.	O
+
+This	O
+report	O
+focused	O
+on	O
+the	O
+relationship	O
+between	O
+Type	O
+A	O
+behavior	O
+and	O
+eight	O
+basic	O
+emotion	O
+dimensions	O
+.	O
+
+All	O
+carcasses	O
+resulted	O
+in	O
+contamination	O
+with	O
+aerobic	O
+mesophilic	O
+bacteria	O
+in	O
+the	O
+range	O
+from	O
+6	O
+x	O
+10	O
+(	O
+3	O
+)	O
+to	O
+1	O
+.	O
+2	O
+x	O
+10	O
+(	O
+6	O
+)	O
+CFU	O
+/	O
+ml	O
+liquid	O
+washed	O
+,	O
+and	O
+94	O
+%	O
+them	O
+with	O
+sporulate	O
+bacteria	O
+,	O
+the	O
+threshold	O
+being	O
+under	O
+100	O
+CFU	O
+/	O
+ml	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+As	O
+for	O
+31	O
+stage	O
+I	O
+-	O
+II	O
+lung	O
+cancer	O
+patients	O
+,	O
+CR	O
+has	O
+been	O
+observed	O
+in	O
+82	O
+.	O
+8	O
+%	O
+of	O
+them	O
+and	O
+PR	O
+in	O
+13	O
+.	O
+8	O
+%	O
+;	O
+the	O
+response	O
+was	O
+always	O
+assessed	O
+with	O
+chest	O
+radiography	O
+,	O
+CT	O
+,	O
+FBS	O
+,	O
+cytology	O
+and	O
+/	O
+or	O
+histology	O
+.	O
+
+Pediatric	O
+medical	O
+emergencies	O
+in	O
+a	O
+regional	O
+hospital	O
+:	O
+appropriate	O
+locale	O
+?	O
+
+Protein	O
+electrophoresis	O
+showed	O
+decreased	O
+albumin	B-GENE
+levels	O
+in	O
+both	O
+groups	O
+,	O
+with	O
+lower	O
+values	O
+in	O
+G2	O
+.	O
+
+METHODS	O
+:	O
+All	O
+these	O
+30	O
+non	O
+-	O
+responders	O
+received	O
+an	O
+extra	O
+dose	O
+of	O
+the	O
+same	O
+vaccine	O
+2	O
+months	O
+after	O
+primary	O
+immunization	O
+and	O
+a	O
+booster	O
+dose	O
+with	O
+a	O
+yeast	O
+-	O
+derived	O
+vaccine	O
+6	O
+years	O
+later	O
+.	O
+
+An	O
+abnormally	O
+high	O
+percentage	O
+of	O
+hypertensive	O
+patients	O
+(	O
+approximately	O
+30	O
+%	O
+)	O
+undergoing	O
+cardiac	O
+catheterization	O
+because	O
+of	O
+anginal	O
+pain	O
+and	O
+/	O
+or	O
+exercise	O
+-	O
+induced	O
+ST	O
+-	O
+segment	O
+depressions	O
+has	O
+angiographically	O
+normal	O
+coronary	O
+arteries	O
+.	O
+
+Mibefradil	O
+(	O
+Ro	O
+40	O
+-	O
+5967	O
+)	O
+is	O
+a	O
+novel	O
+calcium	O
+antagonist	O
+from	O
+a	O
+new	O
+chemical	O
+class	O
+and	O
+is	O
+the	O
+first	O
+that	O
+selectively	O
+blocks	O
+the	O
+T	O
+-	O
+type	O
+calcium	O
+channel	O
+.	O
+
+However	O
+,	O
+2	O
+minimum	O
+alveolar	O
+concentration	O
+anesthesia	O
+did	O
+significantly	O
+decrease	O
+the	O
+calculated	O
+VE	O
+at	O
+a	O
+PCO2	O
+of	O
+60	O
+mmHg	O
+(	O
+from	O
+7	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+to	O
+4	O
+.	O
+0	O
++	O
+/	O
+-	O
+0	O
+.	O
+6	O
+l	O
+.	O
+min	O
+-	O
+1	O
+)	O
+,	O
+indicating	O
+a	O
+rightward	O
+shift	O
+in	O
+the	O
+response	O
+relationship	O
+.	O
+
+cDNA	O
+encoding	O
+a	O
+functional	O
+feline	B-GENE
+liver	I-GENE
+/	I-GENE
+bone	I-GENE
+/	I-GENE
+kidney	I-GENE
+-	I-GENE
+type	I-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+.	O
+
+Protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+(	O
+PKC	B-GENE
+)	O
+,	O
+a	O
+widely	O
+-	O
+distributed	O
+enzyme	O
+implicated	O
+in	O
+the	O
+regulation	O
+of	O
+many	O
+physiological	O
+processes	O
+,	O
+consists	O
+of	O
+a	O
+family	O
+of	O
+at	O
+least	O
+twelve	O
+isoenzymes	O
+which	O
+differ	O
+in	O
+tissue	O
+distribution	O
+,	O
+subcellular	O
+localization	O
+,	O
+regulatory	O
+properties	O
+,	O
+etc	O
+.	O
+
+This	O
+work	O
+,	O
+therefore	O
+,	O
+also	O
+emphasizes	O
+the	O
+importance	O
+of	O
+careful	O
+choice	O
+of	O
+oligonucleotide	O
+and	O
+cDNA	O
+probes	O
+to	O
+study	O
+PKC	B-GENE
+zeta	I-GENE
+mRNA	I-GENE
+.	O
+
+This	O
+action	O
+is	O
+dependent	O
+on	O
+helix	B-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+factors	I-GENE
+bound	O
+to	O
+the	O
+E1	B-GENE
+element	O
+.	O
+
+The	O
+debate	O
+over	O
+electives	O
+-	O
+-	O
+1899	O
+.	O
+
+Polypeptide	O
+growth	O
+factors	O
+and	O
+cytokines	O
+mediate	O
+their	O
+biochemical	O
+functions	O
+through	O
+their	O
+responsive	O
+receptors	O
+.	O
+
+However	O
+,	O
+a	O
+strongly	O
+increased	O
+frequency	O
+of	O
+CpG	O
+dinucleotides	O
+was	O
+found	O
+.	O
+
+During	O
+the	O
+dose	O
+-	O
+finding	O
+,	O
+two	O
+patients	O
+were	O
+temporarily	O
+withdrawn	O
+from	O
+medication	O
+and	O
+one	O
+patient	O
+was	O
+excluded	O
+because	O
+of	O
+elevated	O
+levels	O
+of	O
+liver	O
+enzymes	O
+.	O
+
+In	O
+comparison	O
+of	O
+cDNA	O
+and	O
+genomic	O
+sequences	O
+four	O
+RNA	O
+editing	O
+events	O
+were	O
+found	O
+in	O
+both	O
+atp9	B-GENE
+genes	I-GENE
+.	O
+
+MZF	B-GENE
+-	I-GENE
+1	I-GENE
+represses	O
+CAT	B-GENE
+reporter	I-GENE
+gene	I-GENE
+expression	O
+via	O
+GAL4	B-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+the	O
+nonhematopoietic	O
+cell	O
+lines	O
+NIH	O
+3T3	O
+and	O
+293	O
+.	O
+
+As	O
+with	O
+the	O
+heterologous	O
+DNA	O
+binding	O
+domain	O
+,	O
+MZF	B-GENE
+-	I-GENE
+1	I-GENE
+represses	O
+reporter	O
+gene	O
+expression	O
+in	O
+nonhematopoietic	O
+cell	O
+lines	O
+and	O
+activates	O
+expression	O
+in	O
+hematopoietic	O
+cell	O
+lines	O
+.	O
+
+Analyses	O
+of	O
+hGMR	B-GENE
+beta	I-GENE
+subunit	I-GENE
+mutants	I-GENE
+revealed	O
+two	O
+cytoplasmic	O
+regions	O
+involved	O
+in	O
+activation	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+promoter	I-GENE
+,	O
+one	O
+is	O
+essential	O
+and	O
+the	O
+other	O
+is	O
+dispensable	O
+but	O
+enhances	O
+the	O
+activity	O
+.	O
+
+Similarly	O
+,	O
+we	O
+observed	O
+synthetic	O
+phenotypes	O
+between	O
+mutations	O
+in	O
+MIF2	B-GENE
+and	O
+trans	O
+-	O
+acting	O
+mutations	O
+in	O
+three	O
+known	O
+yeast	O
+centromere	O
+protein	O
+genes	O
+-	O
+CEP1	B-GENE
+/	O
+CBF1	B-GENE
+/	O
+CPF1	B-GENE
+,	O
+NDC10	B-GENE
+/	O
+CBF2	B-GENE
+,	O
+and	O
+CEP3	B-GENE
+/	O
+CBF3B	B-GENE
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+suggest	O
+that	O
+the	O
+Mif2	B-GENE
+protein	I-GENE
+interacts	O
+with	O
+Cep1p	B-GENE
+at	O
+the	O
+centromere	O
+and	O
+that	O
+the	O
+yeast	O
+centromere	O
+indeed	O
+exists	O
+as	O
+a	O
+higher	O
+order	O
+protein	O
+-	O
+DNA	O
+complex	O
+.	O
+
+To	O
+accomplish	O
+this	O
+,	O
+actin	B-GENE
+cables	O
+and	O
+patches	O
+are	O
+redistributed	O
+during	O
+the	O
+cell	O
+cycle	O
+to	O
+direct	O
+secretory	O
+components	O
+to	O
+appropriate	O
+sites	O
+for	O
+cell	O
+growth	O
+.	O
+
+The	O
+effects	O
+of	O
+Codonopsis	O
+pilosula	O
+oral	O
+liquor	O
+(	O
+CPOL	O
+)	O
+on	O
+tissue	B-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+(	O
+t	B-GENE
+-	I-GENE
+PA	I-GENE
+)	O
+and	O
+plasminogen	B-GENE
+activator	I-GENE
+inhibitor	I-GENE
+(	O
+PAI	B-GENE
+)	O
+in	O
+the	O
+plasma	O
+of	O
+25	O
+patients	O
+of	O
+coronary	O
+heart	O
+disease	O
+with	O
+blood	O
+stasis	O
+were	O
+studied	O
+.	O
+
+Estimated	O
+daily	O
+intakes	O
+(	O
+EDIs	O
+)	O
+per	O
+person	O
+were	O
+0	O
+.	O
+56	O
+microgram	O
+for	O
+total	O
+HCH	O
+,	O
+0	O
+.	O
+20	O
+microgram	O
+for	O
+gamma	O
+-	O
+HCH	O
+,	O
+0	O
+.	O
+09	O
+microgram	O
+for	O
+dieldrin	O
+,	O
+1	O
+.	O
+42	O
+micrograms	O
+for	O
+total	O
+DDT	O
+,	O
+and	O
+0	O
+.	O
+15	O
+microgram	O
+for	O
+HCB	O
+.	O
+
+In	O
+two	O
+further	O
+cases	O
+(	O
+one	O
+type	O
+I	O
+and	O
+one	O
+type	O
+III	O
+SMA	O
+)	O
+,	O
+de	O
+novo	O
+deletions	O
+of	O
+only	O
+one	O
+copy	O
+of	O
+Ag1	B-GENE
+-	I-GENE
+CA	I-GENE
+and	O
+C212	B-GENE
+were	O
+found	O
+.	O
+
+With	O
+each	O
+of	O
+the	O
+three	O
+pairs	O
+of	O
+isolates	O
+(	O
+case	O
+and	O
+suspicious	O
+case	O
+)	O
+,	O
+identical	O
+IS6110	O
+banding	O
+patterns	O
+were	O
+found	O
+suggesting	O
+identical	O
+MTB	O
+strains	O
+.	O
+
+HRES	O
+has	O
+been	O
+found	O
+to	O
+be	O
+clinically	O
+useful	O
+in	O
+assessing	O
+histologic	O
+damage	O
+following	O
+pneumatic	O
+dilatation	O
+and	O
+in	O
+localizing	O
+the	O
+LES	O
+during	O
+the	O
+administration	O
+of	O
+intrasphincter	O
+botulinum	B-GENE
+toxin	I-GENE
+injection	O
+in	O
+the	O
+treatment	O
+of	O
+achalasia	O
+.	O
+
+These	O
+early	O
+structural	O
+processes	O
+are	O
+assumed	O
+to	O
+be	O
+subserved	O
+by	O
+the	O
+anterior	O
+parts	O
+of	O
+the	O
+left	O
+hemisphere	O
+,	O
+as	O
+event	O
+-	O
+related	O
+brain	O
+potentials	O
+show	O
+this	O
+area	O
+to	O
+be	O
+maximally	O
+activated	O
+when	O
+phrase	O
+structure	O
+violations	O
+are	O
+processed	O
+and	O
+as	O
+circumscribed	O
+lesions	O
+in	O
+this	O
+area	O
+lead	O
+to	O
+an	O
+impairment	O
+of	O
+the	O
+on	O
+-	O
+line	O
+structural	O
+assignment	O
+.	O
+
+In	O
+men	O
+with	O
+BMI	O
+<	O
+30	O
+,	O
+the	O
+OR	O
+was	O
+1	O
+.	O
+83	O
+for	O
+postprandial	O
+TG	O
+(	O
+P	O
+=	O
+.	O
+041	O
+)	O
+and	O
+2	O
+.	O
+77	O
+for	O
+postprandial	O
+RP	O
+(	O
+P	O
+=	O
+.	O
+032	O
+)	O
+in	O
+models	O
+that	O
+included	O
+fasting	O
+TG	O
+,	O
+LDL	B-GENE
+-	I-GENE
+C	I-GENE
+,	O
+and	O
+hypertension	O
+.	O
+
+A	O
+pyrazolo	O
+-	O
+quinoline	O
+compound	O
+,	O
+6	O
+-	O
+methoxy	O
+-	O
+4	O
+-	O
+[	O
+2	O
+-	O
+[	O
+(	O
+2	O
+-	O
+hydroxyethoxyl	O
+)	O
+-	O
+ethyl	O
+]	O
+amino	O
+]	O
+-	O
+3	O
+-	O
+methyl	O
+-	O
+1M	O
+-	O
+pyrazo	O
+lo	O
+[	O
+3	O
+,	O
+4	O
+-	O
+b	O
+]	O
+quinoline	O
+(	O
+SCH	O
+51344	O
+)	O
+,	O
+was	O
+identified	O
+based	O
+on	O
+its	O
+ability	O
+to	O
+derepress	O
+human	O
+smooth	O
+muscle	O
+alpha	B-GENE
+-	I-GENE
+actin	I-GENE
+promoter	I-GENE
+activity	O
+in	O
+ras	B-GENE
+-	O
+transformed	O
+cells	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+these	O
+relations	O
+,	O
+a	O
+risk	O
+factor	O
+-	O
+selection	O
+scale	O
+(	O
+RFSS	O
+)	O
+(	O
+range	O
+,	O
+0	O
+to	O
+10	O
+)	O
+was	O
+developed	O
+by	O
+computing	O
+appropriate	O
+weights	O
+for	O
+each	O
+risk	O
+factor	O
+.	O
+
+The	O
+Caenorhabditis	B-GENE
+elegans	I-GENE
+death	I-GENE
+susceptibility	I-GENE
+gene	I-GENE
+,	O
+ced	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+has	O
+a	O
+number	O
+of	O
+homologs	O
+in	O
+vertebrate	O
+species	O
+,	O
+including	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+(	I-GENE
+IL	I-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+)	I-GENE
+-	I-GENE
+converting	I-GENE
+enzyme	I-GENE
+(	O
+ICE	B-GENE
+)	O
+,	O
+Ich	B-GENE
+-	I-GENE
+1long	I-GENE
+,	O
+and	O
+CPP32	B-GENE
+.	O
+
+Repression	O
+of	O
+glucocorticoid	B-GENE
+receptor	I-GENE
+-	O
+mediated	O
+transcriptional	O
+activation	O
+by	O
+unliganded	O
+thyroid	B-GENE
+hormone	I-GENE
+receptor	I-GENE
+(	O
+TR	B-GENE
+)	O
+is	O
+TR	B-GENE
+isoform	O
+-	O
+specific	O
+.	O
+
+The	O
+results	O
+indicate	O
+considerable	O
+flexibility	O
+in	O
+the	O
+spacing	O
+between	O
+DH	B-GENE
+regulatory	O
+sites	O
+.	O
+
+Obstruction	O
+of	O
+the	O
+ERF	B-GENE
+repressor	I-GENE
+function	O
+by	O
+the	O
+transactivating	O
+members	O
+of	O
+the	O
+ets	B-GENE
+family	I-GENE
+of	O
+genes	O
+(	O
+i	O
+.	O
+e	O
+.	O
+gag	B-GENE
+-	O
+myb	B-GENE
+-	O
+ets	B-GENE
+)	O
+may	O
+be	O
+essential	O
+for	O
+the	O
+control	O
+of	O
+genes	O
+involved	O
+in	O
+cell	O
+proliferation	O
+and	O
+may	O
+also	O
+underlie	O
+their	O
+tumorigenic	O
+effects	O
+.	O
+
+We	O
+show	O
+that	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+(	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+protooncogene	I-GENE
+product	I-GENE
+)	O
+,	O
+which	O
+is	O
+an	O
+intrinsically	O
+unstable	O
+nuclear	O
+protein	O
+,	O
+is	O
+metabolically	O
+highly	O
+stabilized	O
+,	O
+and	O
+greatly	O
+enhances	O
+the	O
+transforming	O
+efficiency	O
+of	O
+NIH	O
+3T3	O
+cells	O
+,	O
+by	O
+Mos	B-GENE
+.	O
+
+Cloning	O
+,	O
+sequencing	O
+and	O
+expression	O
+of	O
+the	O
+3	B-GENE
+-	I-GENE
+phosphoglycerate	I-GENE
+kinase	I-GENE
+gene	I-GENE
+of	O
+Pyrococcus	O
+woesei	O
+in	O
+Escherichia	O
+coli	O
+and	O
+characterization	O
+of	O
+the	O
+protein	O
+.	O
+
+We	O
+sought	O
+to	O
+determine	O
+whether	O
+such	O
+differences	O
+in	O
+polyadenylation	O
+affect	O
+the	O
+steady	O
+-	O
+state	O
+levels	O
+of	O
+DHFR	B-GENE
+and	O
+mRNAs	O
+expressed	O
+from	O
+either	O
+allele	O
+and	O
+,	O
+in	O
+a	O
+more	O
+general	O
+sense	O
+,	O
+to	O
+ask	O
+whether	O
+differences	O
+in	O
+3	O
+'	O
+end	O
+RNA	O
+processing	O
+in	O
+a	O
+gene	O
+containing	O
+multiple	O
+poly	O
+(	O
+A	O
+)	O
+sites	O
+affects	O
+the	O
+final	O
+level	O
+of	O
+gene	O
+expression	O
+.	O
+
+The	O
+finding	O
+that	O
+the	O
+chimeric	B-GENE
+TdT	I-GENE
+:	O
+:	O
+Pol	B-GENE
+beta	I-GENE
+protein	I-GENE
+possessed	O
+significant	O
+template	O
+-	O
+dependent	O
+polymerase	O
+activity	O
+suggests	O
+that	O
+aa	O
+1	O
+-	O
+60	O
+of	O
+Pol	B-GENE
+beta	I-GENE
+are	O
+involved	O
+in	O
+template	O
+utilization	O
+during	O
+the	O
+polymerization	O
+reaction	O
+,	O
+as	O
+suggested	O
+by	O
+the	O
+previous	O
+finding	O
+that	O
+the	O
+8	O
+-	O
+kDa	O
+N	O
+-	O
+terminal	O
+domain	O
+of	O
+Pol	B-GENE
+beta	I-GENE
+possesses	O
+ssDNA	O
+-	O
+binding	O
+activity	O
+[	O
+Kumar	O
+et	O
+al	O
+.	O
+,	O
+J	O
+.	O
+
+The	O
+average	O
+values	O
+were	O
+199	O
+and	O
+424	O
+revertants	O
+/	O
+g	O
+for	O
+the	O
+hamburgers	O
+and	O
+hot	O
+dogs	O
+,	O
+respectively	O
+.	O
+
+Cholangiography	O
+was	O
+performed	O
+in	O
+all	O
+cases	O
+and	O
+classified	O
+by	O
+a	O
+scoring	O
+system	O
+specifically	O
+developed	O
+for	O
+pediatric	O
+patients	O
+.	O
+
+In	O
+Trial	O
+1	O
+,	O
+eight	O
+sows	O
+were	O
+allowed	O
+to	O
+farrow	O
+naturally	O
+(	O
+d	O
+114	O
+,	O
+NF	O
+sows	O
+)	O
+and	O
+eight	O
+sows	O
+were	O
+induced	O
+to	O
+farrow	O
+(	O
+IF	O
+sows	O
+)	O
+prematurely	O
+by	O
+injection	O
+of	O
+prostaglandin	O
+F2	O
+alpha	O
+on	O
+d	O
+112	O
+of	O
+gestation	O
+.	O
+
+End	O
+-	O
+tidal	O
+PO2	O
+and	O
+the	O
+ratio	O
+of	O
+minute	O
+ventilation	O
+to	O
+oxygen	O
+consumption	O
+(	O
+VE	O
+/	O
+VO2	O
+)	O
+were	O
+lower	O
+while	O
+PETCO2	O
+was	O
+higher	O
+for	O
+Hyp	O
+(	O
+P	O
+<	O
+or	O
+=	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+These	O
+results	O
+suggested	O
+that	O
+NfxB	B-GENE
+negatively	O
+autoregulates	O
+the	O
+expression	O
+of	O
+nfxB	B-GENE
+itself	O
+.	O
+
+A511	O
+is	O
+a	O
+broad	O
+-	O
+host	O
+-	O
+range	O
+,	O
+virulent	O
+myovirus	O
+for	O
+Listeria	O
+monocytogenes	O
+.	O
+
+The	O
+mechanism	O
+of	O
+peroxisome	O
+proliferation	O
+is	O
+poorly	O
+understood	O
+.	O
+
+If	O
+NCR	O
+-	O
+sensitive	O
+gene	O
+expression	O
+occurs	O
+exclusively	O
+by	O
+this	O
+pathway	O
+,	O
+as	O
+has	O
+been	O
+thought	O
+to	O
+be	O
+the	O
+case	O
+,	O
+then	O
+the	O
+NCR	O
+sensitivity	O
+of	O
+a	O
+gene	O
+'	O
+s	O
+expression	O
+should	O
+be	O
+abolished	O
+by	O
+a	O
+ure2	B-GENE
+delta	I-GENE
+mutation	I-GENE
+.	O
+
+The	O
+single	O
+-	O
+stranded	O
+DNA	O
+Pur	B-GENE
+alpha	I-GENE
+recognition	I-GENE
+element	I-GENE
+disrupts	O
+these	O
+complexes	O
+.	O
+
+Association	O
+of	O
+human	B-GENE
+Pur	I-GENE
+alpha	I-GENE
+with	O
+the	O
+retinoblastoma	B-GENE
+protein	I-GENE
+,	O
+Rb	B-GENE
+,	O
+regulates	O
+binding	O
+to	O
+the	O
+single	O
+-	O
+stranded	O
+DNA	O
+Pur	B-GENE
+alpha	I-GENE
+recognition	I-GENE
+element	I-GENE
+.	O
+
+The	O
+insulin	B-GENE
+-	O
+induced	O
+DNA	O
+-	O
+binding	O
+complex	O
+was	O
+identified	O
+as	O
+the	O
+p50	B-GENE
+/	O
+p65	B-GENE
+heterodimer	O
+.	O
+
+Using	O
+varying	O
+conditions	O
+,	O
+three	O
+distinct	O
+complexes	O
+were	O
+shown	O
+to	O
+interact	O
+specifically	O
+with	O
+the	O
+NIP	B-GENE
+region	I-GENE
+,	O
+although	O
+only	O
+one	O
+correlates	O
+with	O
+repressor	O
+activity	O
+.	O
+
+Exchange	O
+of	O
+the	O
+LPL	B-GENE
+and	O
+HL	B-GENE
+lids	O
+resulted	O
+in	O
+a	O
+reversal	O
+of	O
+the	O
+phospholipase	B-GENE
+/	O
+neutral	O
+lipase	B-GENE
+ratio	O
+,	O
+establishing	O
+the	O
+important	O
+role	O
+of	O
+this	O
+region	O
+in	O
+mediating	O
+substrate	O
+specificity	O
+.	O
+
+The	O
+interferon	B-GENE
+-	O
+inducible	O
+protein	B-GENE
+kinase	I-GENE
+PKR	I-GENE
+modulates	O
+the	O
+transcriptional	O
+activation	O
+of	O
+immunoglobulin	B-GENE
+kappa	I-GENE
+gene	I-GENE
+.	O
+
+Truncated	O
+forms	O
+of	O
+a	O
+novel	O
+yeast	O
+protein	O
+suppress	O
+the	O
+lethality	O
+of	O
+a	O
+G	B-GENE
+protein	I-GENE
+alpha	I-GENE
+subunit	I-GENE
+deficiency	O
+by	O
+interacting	O
+with	O
+the	O
+beta	O
+subunit	O
+.	O
+
+Another	O
+common	O
+mutation	O
+involved	O
+amino	O
+acids	O
+that	O
+are	O
+thought	O
+to	O
+make	O
+specific	O
+contacts	O
+with	O
+DNA	O
+.	O
+
+Levels	O
+of	O
+TSG	B-GENE
+-	I-GENE
+14	I-GENE
+protein	I-GENE
+(	O
+also	O
+termed	O
+PTX	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+become	O
+elevated	O
+in	O
+the	O
+serum	O
+of	O
+mice	O
+and	O
+humans	O
+after	O
+injection	O
+with	O
+bacterial	O
+lipopolysaccharide	O
+,	O
+but	O
+in	O
+contrast	O
+to	O
+conventional	O
+acute	O
+phase	O
+proteins	O
+,	O
+the	O
+bulk	O
+of	O
+TSG	B-GENE
+-	I-GENE
+14	I-GENE
+synthesis	O
+in	O
+the	O
+intact	O
+organism	O
+occurs	O
+outside	O
+the	O
+liver	O
+.	O
+
+The	O
+mouse	B-GENE
+beta	I-GENE
+2	I-GENE
+-	I-GENE
+syntrophin	I-GENE
+gene	I-GENE
+(	O
+>	O
+33	O
+kilobases	O
+)	O
+contains	O
+seven	O
+exons	O
+,	O
+all	O
+of	O
+which	O
+have	O
+homologues	O
+at	O
+the	O
+corresponding	O
+position	O
+in	O
+the	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+syntrophin	I-GENE
+gene	I-GENE
+.	O
+
+Altogether	O
+our	O
+data	O
+indicate	O
+that	O
+PEDF	B-GENE
+belongs	O
+to	O
+the	O
+subgroup	O
+of	O
+noninhibitory	O
+serpins	B-GENE
+and	O
+that	O
+its	O
+N	O
+-	O
+terminal	O
+region	O
+confers	O
+a	O
+neurite	O
+-	O
+promoting	O
+activity	O
+to	O
+the	O
+protein	O
+.	O
+
+We	O
+report	O
+here	O
+the	O
+cloning	O
+of	O
+the	O
+murine	O
+p44	B-GENE
+MAP	B-GENE
+kinase	I-GENE
+(	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+1	I-GENE
+)	O
+gene	O
+,	O
+the	O
+determination	O
+of	O
+its	O
+intron	O
+/	O
+exon	O
+boundaries	O
+,	O
+and	O
+the	O
+characterization	O
+of	O
+its	O
+promoter	O
+.	O
+
+It	O
+contains	O
+three	O
+putative	O
+TATA	O
+boxes	O
+far	O
+upstream	O
+of	O
+the	O
+main	O
+start	O
+sites	O
+region	O
+,	O
+one	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+box	I-GENE
+,	O
+one	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+box	I-GENE
+,	O
+one	O
+Malt	B-GENE
+box	I-GENE
+,	O
+one	O
+GAGA	O
+box	O
+,	O
+one	O
+half	O
+serum	O
+-	O
+responsive	O
+element	O
+,	O
+and	O
+putative	O
+binding	O
+sites	O
+for	O
+Sp1	B-GENE
+(	O
+five	O
+)	O
+,	O
+GC	B-GENE
+-	I-GENE
+rich	I-GENE
+binding	I-GENE
+factor	I-GENE
+(	O
+five	O
+)	O
+,	O
+CTF	B-GENE
+-	I-GENE
+NF1	I-GENE
+(	O
+one	O
+)	O
+,	O
+Myb	B-GENE
+(	O
+one	O
+)	O
+,	O
+p53	B-GENE
+(	O
+two	O
+)	O
+,	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+(	O
+one	O
+)	O
+,	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+(	O
+two	O
+)	O
+,	O
+MyoD	B-GENE
+(	O
+two	O
+)	O
+,	O
+Zeste	B-GENE
+(	O
+one	O
+)	O
+,	O
+and	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factor	I-GENE
+-	I-GENE
+5	I-GENE
+(	O
+one	O
+)	O
+.	O
+
+We	O
+conclude	O
+that	O
+this	O
+new	O
+measurement	O
+technique	O
+provides	O
+an	O
+easy	O
+and	O
+accurate	O
+P0	O
+.	O
+1	O
+measurement	O
+using	O
+standard	O
+respiratory	O
+equipment	O
+when	O
+tested	O
+in	O
+a	O
+lung	O
+model	O
+.	O
+
+Effects	O
+of	O
+verapamil	O
+and	O
+propranolol	O
+on	O
+early	O
+afterdepolarizations	O
+and	O
+ventricular	O
+arrhythmias	O
+induced	O
+by	O
+epinephrine	O
+in	O
+congenital	O
+long	O
+QT	O
+syndrome	O
+.	O
+
+Deletion	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+beta	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+domain	I-GENE
+also	O
+greatly	O
+diminished	O
+the	O
+interaction	O
+between	O
+these	O
+two	O
+proteins	O
+.	O
+
+After	O
+cells	O
+were	O
+stably	O
+transfected	O
+with	O
+CIITA	B-GENE
+,	O
+endogenous	O
+MHC	B-GENE
+class	I-GENE
+II	I-GENE
+genes	I-GENE
+were	O
+constitutively	O
+expressed	O
+,	O
+and	O
+MHC	B-GENE
+class	I-GENE
+II	I-GENE
+promoters	I-GENE
+,	O
+delivered	O
+by	O
+transfection	O
+,	O
+were	O
+actively	O
+transcribed	O
+in	O
+CIITA	B-GENE
+-	O
+expressing	O
+cells	O
+.	O
+
+Two	O
+domains	O
+of	O
+EBNA2	B-GENE
+defined	O
+by	O
+deletion	O
+of	O
+amino	O
+acids	O
+247	O
+-	O
+337	O
+and	O
+437	O
+-	O
+476	O
+were	O
+found	O
+to	O
+be	O
+important	O
+for	O
+the	O
+activation	O
+of	O
+both	O
+promoters	O
+,	O
+while	O
+two	O
+different	O
+domains	O
+corresponding	O
+to	O
+residues	O
+4	O
+-	O
+18	O
+and	O
+118	O
+-	O
+198	O
+were	O
+required	O
+solely	O
+for	O
+the	O
+LMP1	B-GENE
+promoter	I-GENE
+.	O
+
+The	O
+peak	O
+velocities	O
+of	O
+the	O
+atrial	O
+systolic	O
+waves	O
+of	O
+the	O
+transmitral	O
+and	O
+pulmonary	O
+venous	O
+flow	O
+velocities	O
+(	O
+A	O
+and	O
+PVA	O
+,	O
+respectively	O
+)	O
+and	O
+first	O
+systolic	O
+wave	O
+(	O
+PVS1	O
+)	O
+of	O
+pulmonary	O
+venous	O
+flow	O
+,	O
+durations	O
+of	O
+both	O
+atrial	O
+systolic	O
+waves	O
+,	O
+and	O
+amplitude	O
+of	O
+interatrial	O
+septal	O
+motion	O
+during	O
+atrial	O
+systole	O
+increased	O
+significantly	O
+ten	O
+days	O
+after	O
+cardioversion	O
+compared	O
+with	O
+those	O
+measured	O
+within	O
+a	O
+day	O
+of	O
+cardioversion	O
+in	O
+all	O
+patients	O
+except	O
+the	O
+5	O
+patients	O
+with	O
+dilated	O
+cardiomyopathy	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+low	O
+concentrations	O
+of	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+may	O
+be	O
+useful	O
+for	O
+nonsurgical	O
+treatment	O
+of	O
+human	O
+vitreous	O
+hemorrhage	O
+.	O
+
+We	O
+conclude	O
+that	O
+pancreatic	O
+polypeptide	O
+and	O
+motilin	B-GENE
+responses	O
+to	O
+a	O
+meal	O
+are	O
+different	O
+in	O
+encopretic	O
+children	O
+than	O
+in	O
+children	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+cloning	O
+,	O
+expression	O
+,	O
+and	O
+biochemical	O
+characterization	O
+of	O
+the	O
+32	O
+-	O
+kDa	O
+subunit	O
+of	O
+human	O
+(	O
+h	O
+)	O
+TFIID	B-GENE
+,	O
+termed	O
+hTAFII32	B-GENE
+.	O
+
+Hemolytic	O
+jaundice	O
+due	O
+to	O
+G6PD	B-GENE
+deficiency	O
+causing	O
+kernicterus	O
+in	O
+a	O
+female	O
+newborn	O
+.	O
+
+Two	O
+transcripts	O
+of	O
+1	O
+.	O
+6	O
+kb	O
+and	O
+5	O
+.	O
+8	O
+kb	O
+are	O
+5	O
+'	O
+coterminal	O
+and	O
+may	O
+both	O
+encode	O
+the	O
+novel	O
+glycoprotein	B-GENE
+gene	I-GENE
+EUS4	I-GENE
+.	O
+
+However	O
+,	O
+the	O
+few	O
+studies	O
+that	O
+address	O
+antimicrobial	O
+prophylaxis	O
+in	O
+bone	O
+marrow	O
+transplantation	O
+have	O
+not	O
+always	O
+shown	O
+a	O
+survival	O
+benefit	O
+.	O
+
+The	O
+fracture	O
+groups	O
+were	O
+significantly	O
+older	O
+and	O
+had	O
+more	O
+years	O
+since	O
+menopause	O
+than	O
+the	O
+control	O
+groups	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+found	O
+differences	O
+in	O
+the	O
+binding	O
+of	O
+nuclear	O
+factors	O
+from	O
+shoots	O
+versus	O
+from	O
+roots	O
+,	O
+in	O
+agreement	O
+with	O
+the	O
+different	O
+activities	O
+of	O
+the	O
+promoter	O
+in	O
+these	O
+two	O
+organs	O
+.	O
+
+The	O
+prevalence	O
+and	O
+incidence	O
+of	O
+human	O
+immunodeficiency	O
+virus	O
+types	O
+1	O
+and	O
+2	O
+(	O
+HIV	O
+-	O
+1	O
+,	O
+HIV	O
+-	O
+2	O
+)	O
+,	O
+human	O
+T	O
+-	O
+lymphotropic	O
+virus	O
+types	O
+I	O
+and	O
+II	O
+(	O
+HTLV	O
+-	O
+I	O
+/	O
+II	O
+)	O
+,	O
+and	O
+syphilitic	O
+infections	O
+and	O
+the	O
+association	O
+between	O
+these	O
+infections	O
+were	O
+determined	O
+in	O
+a	O
+cohort	O
+of	O
+police	O
+officers	O
+in	O
+Guinea	O
+-	O
+Bissau	O
+.	O
+
+We	O
+now	O
+show	O
+that	O
+the	O
+BAT1	B-GENE
+translation	I-GENE
+product	I-GENE
+is	O
+the	O
+homolog	O
+of	O
+the	O
+rat	B-GENE
+p47	I-GENE
+nuclear	I-GENE
+protein	I-GENE
+,	O
+the	O
+WM6	B-GENE
+Drosophila	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+and	O
+probably	O
+also	O
+Ce08102	B-GENE
+of	O
+Caenorhabditis	O
+elegans	O
+,	O
+all	O
+members	O
+of	O
+the	O
+DEAD	B-GENE
+protein	I-GENE
+family	I-GENE
+of	O
+ATP	B-GENE
+-	I-GENE
+dependent	I-GENE
+RNA	I-GENE
+helicases	I-GENE
+.	O
+
+By	O
+using	O
+lacZ	B-GENE
+fusions	I-GENE
+,	O
+it	O
+was	O
+possible	O
+to	O
+localize	O
+the	O
+DNA	O
+sequences	O
+required	O
+to	O
+mediate	O
+nitrate	O
+repression	O
+to	O
+the	O
+pfl	B-GENE
+promoter	I-GENE
+-	I-GENE
+regulatory	I-GENE
+region	I-GENE
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+describe	O
+the	O
+characterization	O
+of	O
+two	O
+early	O
+class	B-GENE
+II	I-GENE
+flagellar	I-GENE
+genes	I-GENE
+contained	O
+in	O
+the	O
+orfX	O
+-	O
+fliP	B-GENE
+locus	O
+.	O
+
+Vestibular	O
+adaptation	O
+exercises	O
+and	O
+recovery	O
+:	O
+acute	O
+stage	O
+after	O
+acoustic	O
+neuroma	O
+resection	O
+.	O
+
+There	O
+were	O
+no	O
+significant	O
+changes	O
+in	O
+either	O
+the	O
+fatty	O
+acid	O
+composition	O
+of	O
+biliary	O
+lecithin	O
+or	O
+in	O
+the	O
+bile	O
+acid	O
+composition	O
+of	O
+bile	O
+.	O
+
+Although	O
+further	O
+studies	O
+are	O
+required	O
+to	O
+determine	O
+the	O
+precise	O
+role	O
+of	O
+PEBP2	B-GENE
+in	O
+the	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+promoter	I-GENE
+activity	O
+,	O
+the	O
+present	O
+findings	O
+suggested	O
+the	O
+importance	O
+of	O
+the	O
+relative	O
+ratio	O
+of	O
+different	O
+PEBP2	B-GENE
+isoforms	I-GENE
+in	O
+regulating	O
+the	O
+levels	O
+of	O
+the	O
+promoter	O
+activity	O
+.	O
+
+Benefits	O
+of	O
+obtaining	O
+board	O
+certification	O
+in	O
+pharmacotherapy	O
+.	O
+
+Basal	O
+plasma	O
+renin	B-GENE
+activity	O
+(	O
+PRA	O
+)	O
+was	O
+slightly	O
+raised	O
+prior	O
+to	O
+training	O
+(	O
+P	O
+<	O
+0	O
+.	O
+07	O
+)	O
+compared	O
+to	O
+the	O
+controls	O
+and	O
+post	O
+-	O
+training	O
+.	O
+
+The	O
+structural	O
+gene	O
+encoding	O
+the	O
+novel	O
+lantibiotic	O
+epilancin	B-GENE
+K7	I-GENE
+from	O
+Staphylococcus	O
+epidermidis	O
+K7	O
+was	O
+cloned	O
+and	O
+its	O
+nucleotide	O
+sequence	O
+was	O
+determined	O
+.	O
+
+The	O
+spectrum	O
+of	O
+phenotypes	O
+caused	O
+by	O
+these	O
+mutations	O
+was	O
+strikingly	O
+different	O
+than	O
+mutations	O
+in	O
+the	O
+adaptor	O
+for	O
+the	O
+VP16	B-GENE
+activation	I-GENE
+domain	I-GENE
+.	O
+
+The	O
+5	O
+'	O
+flanking	O
+region	O
+is	O
+highly	O
+GC	O
+rich	O
+,	O
+with	O
+multiple	O
+CpG	O
+doublets	O
+,	O
+and	O
+contains	O
+multiple	O
+binding	O
+sites	O
+for	O
+Sp1	B-GENE
+.	O
+
+To	O
+discern	O
+whether	O
+these	O
+disorders	O
+of	O
+GnRH	B-GENE
+deficiency	O
+are	O
+associated	O
+with	O
+altered	O
+melatonin	O
+secretion	O
+profiles	O
+,	O
+we	O
+compared	O
+untreated	O
+young	O
+males	O
+IGD	O
+(	O
+n	O
+=	O
+7	O
+)	O
+and	O
+DP	O
+(	O
+n	O
+=	O
+7	O
+)	O
+to	O
+normal	O
+pubertal	O
+male	O
+controls	O
+(	O
+n	O
+=	O
+6	O
+)	O
+.	O
+
+Increased	O
+blood	O
+pressure	O
+during	O
+CyA	O
+treatment	O
+was	O
+independent	O
+of	O
+circulating	O
+ET	B-GENE
+-	I-GENE
+1	I-GENE
+levels	O
+.	O
+
+Analysis	O
+of	O
+several	O
+Tat	B-GENE
+mutants	I-GENE
+indicated	O
+that	O
+both	O
+the	O
+cysteine	O
+-	O
+rich	O
+and	O
+the	O
+core	O
+domains	O
+of	O
+this	O
+transactivator	O
+are	O
+necessary	O
+and	O
+sufficient	O
+to	O
+activate	O
+transcription	O
+when	O
+TBP	B-GENE
+is	O
+overexpressed	O
+.	O
+
+In	O
+addition	O
+,	O
+depletion	O
+of	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+from	O
+the	O
+nuclear	O
+extract	O
+by	O
+using	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+specific	O
+antiserum	O
+or	O
+a	O
+sequence	O
+-	O
+specific	O
+DNA	O
+affinity	O
+resin	O
+decreased	O
+in	O
+vitro	O
+transcription	O
+from	O
+the	O
+wild	O
+-	O
+type	O
+MMTV	O
+promoter	O
+to	O
+a	O
+level	O
+identical	O
+to	O
+that	O
+obtained	O
+from	O
+a	O
+promoter	O
+in	O
+which	O
+all	O
+three	O
+octamer	O
+-	O
+related	O
+sequences	O
+were	O
+mutated	O
+.	O
+
+Transactivation	O
+of	O
+the	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+LTR	I-GENE
+by	O
+T3R	B-GENE
+alpha	I-GENE
+and	O
+several	O
+receptor	O
+mutants	O
+revealed	O
+that	O
+the	O
+50	O
+-	O
+amino	O
+-	O
+acid	O
+N	O
+-	O
+terminal	O
+A	O
+/	O
+B	O
+region	O
+of	O
+T3R	B-GENE
+alpha	I-GENE
+,	O
+known	O
+to	O
+interact	O
+with	O
+the	O
+basal	B-GENE
+transcription	I-GENE
+factor	I-GENE
+TFIIB	I-GENE
+,	O
+is	O
+critical	O
+for	O
+activation	O
+of	O
+both	O
+Tat	B-GENE
+-	O
+dependent	O
+and	O
+Tat	B-GENE
+-	O
+independent	O
+responsive	O
+sequences	O
+of	O
+the	O
+LTR	O
+.	O
+
+M	O
+.	O
+M	O
+.	O
+C	O
+.	O
+was	O
+used	O
+for	O
+2	O
+.	O
+5	O
+minutes	O
+in	O
+44	O
+cases	O
+(	O
+20	O
+HR	O
+patients	O
+,	O
+24	O
+LR	O
+patients	O
+)	O
+,	O
+and	O
+for	O
+5	O
+minutes	O
+in	O
+66	O
+cases	O
+(	O
+46	O
+HR	O
+patients	O
+,	O
+20	O
+LR	O
+patients	O
+)	O
+.	O
+
+Finally	O
+,	O
+we	O
+show	O
+that	O
+complexes	O
+similar	O
+to	O
+the	O
+C25	B-GENE
+,	O
+C30	B-GENE
+and	O
+C35	B-GENE
+complexes	I-GENE
+are	O
+formed	O
+by	O
+rat	O
+cortex	O
+nuclear	O
+extracts	O
+and	O
+the	O
+SAA	O
+element	O
+in	O
+EMSA	O
+experiments	O
+,	O
+suggesting	O
+the	O
+relevance	O
+of	O
+our	O
+in	O
+vitro	O
+observations	O
+to	O
+the	O
+in	O
+vivo	O
+functioning	O
+of	O
+the	O
+rat	B-GENE
+APP	I-GENE
+promoter	I-GENE
+.	O
+
+Oncological	O
+,	O
+clinical	O
+and	O
+psychological	O
+aspects	O
+are	O
+evaluated	O
+according	O
+to	O
+experience	O
+accumulated	O
+in	O
+recent	O
+years	O
+,	O
+with	O
+immediate	O
+and	O
+delayed	O
+reconstruction	O
+,	O
+carried	O
+out	O
+in	O
+the	O
+most	O
+diverse	O
+specialized	O
+centers	O
+.	O
+
+The	O
+analysis	O
+of	O
+the	O
+prevalence	O
+values	O
+shows	O
+clearly	O
+that	O
+the	O
+global	O
+MS	O
+-	O
+frequency	O
+is	O
+closer	O
+related	O
+to	O
+the	O
+geomagnetic	O
+than	O
+to	O
+the	O
+geographic	O
+latitude	O
+.	O
+
+Diltiazem	O
+caused	O
+significant	O
+decrease	O
+in	O
+the	O
+ventricular	O
+response	O
+without	O
+conversion	O
+to	O
+sinus	O
+rhythm	O
+.	O
+
+Subhuman	O
+primates	O
+appear	O
+to	O
+be	O
+more	O
+sensitive	O
+to	O
+reproductive	O
+and	O
+other	O
+adverse	O
+effects	O
+of	O
+PCBs	O
+than	O
+humans	O
+.	O
+
+When	O
+excluding	O
+children	O
+with	O
+ocular	O
+and	O
+cerebral	O
+pathology	O
+,	O
+32	O
+matched	O
+pairs	O
+of	O
+premature	O
+and	O
+control	O
+children	O
+remained	O
+.	O
+
+The	O
+cryptococcal	B-GENE
+antigen	I-GENE
+test	O
+was	O
+positive	O
+at	O
+1	O
+:	O
+125	O
+by	O
+latex	O
+agglutination	O
+.	O
+
+Functional	O
+analysis	O
+of	O
+DNase	B-GENE
+-	I-GENE
+I	I-GENE
+hypersensitive	O
+sites	O
+at	O
+the	O
+mouse	B-GENE
+porphobilinogen	I-GENE
+deaminase	I-GENE
+gene	I-GENE
+locus	I-GENE
+.	O
+
+These	O
+transcripts	O
+have	O
+a	O
+unique	O
+5	O
+'	O
+untranslated	O
+region	O
+and	O
+NH2	O
+-	O
+terminal	O
+sequence	O
+and	O
+encode	O
+a	O
+predicted	O
+protein	O
+of	O
+121	O
+kD	O
+.	O
+
+Both	O
+mu	B-GENE
+and	I-GENE
+gamma	I-GENE
+2b	I-GENE
+heavy	I-GENE
+chain	I-GENE
+genes	I-GENE
+cause	O
+this	O
+feedback	O
+inhibition	O
+of	O
+heavy	O
+chain	O
+gene	O
+rearrangement	O
+.	O
+
+Purified	O
+CarP	B-GENE
+binds	O
+in	O
+vitro	O
+to	O
+the	O
+carAB	B-GENE
+control	I-GENE
+region	I-GENE
+and	O
+protects	O
+against	O
+DNase	B-GENE
+I	I-GENE
+two	O
+approximately	O
+25	O
+bp	O
+long	O
+stretches	O
+,	O
+one	O
+of	O
+which	O
+is	O
+located	O
+just	O
+downstream	O
+of	O
+the	O
+GATC	O
+sequence	O
+.	O
+
+They	O
+include	O
+genes	O
+encoding	O
+three	O
+subunits	O
+of	O
+the	O
+cytochrome	B-GENE
+oxidase	I-GENE
+(	O
+cox1	B-GENE
+to	I-GENE
+3	I-GENE
+)	O
+,	O
+apocytochrome	B-GENE
+b	I-GENE
+(	O
+cob	B-GENE
+)	O
+,	O
+seven	O
+subunits	O
+of	O
+the	O
+NADH	B-GENE
+dehydrogenase	I-GENE
+complex	I-GENE
+(	O
+nad1	B-GENE
+to	I-GENE
+6	I-GENE
+,	O
+nad4L	B-GENE
+)	O
+,	O
+two	O
+ATPase	B-GENE
+subunits	O
+(	O
+atp6	B-GENE
+and	O
+atp9	B-GENE
+)	O
+,	O
+three	O
+ribosomal	O
+RNAs	O
+(	O
+rrn5	B-GENE
+,	O
+srn	B-GENE
+and	O
+lrn	B-GENE
+)	O
+,	O
+23	O
+tRNAs	O
+and	O
+four	O
+ribosomal	O
+proteins	O
+(	O
+rps3	B-GENE
+,	O
+rps11	B-GENE
+,	O
+rps12	B-GENE
+and	O
+rpl16	B-GENE
+)	O
+.	O
+
+From	O
+day	O
+10	O
+,	O
+a	O
+significant	O
+increase	O
+in	O
+platelet	O
+count	O
+was	O
+observed	O
+in	O
+eight	O
+of	O
+the	O
+ten	O
+patients	O
+treated	O
+with	O
+heparin	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+with	O
+return	O
+to	O
+the	O
+initial	O
+value	O
+after	O
+heparin	O
+cessation	O
+in	O
+six	O
+of	O
+the	O
+responders	O
+.	O
+
+These	O
+"	O
+nucleocapsid	O
+-	O
+like	O
+"	O
+structures	O
+were	O
+readily	O
+purified	O
+by	O
+density	O
+gradient	O
+centrifugation	O
+.	O
+
+Resources	O
+for	O
+helping	O
+patients	O
+to	O
+quit	O
+smoking	O
+.	O
+
+The	O
+PEBP2	B-GENE
+alpha	I-GENE
+proteins	I-GENE
+contain	O
+a	O
+128	O
+-	O
+amino	O
+-	O
+acid	O
+(	O
+aa	O
+)	O
+region	O
+highly	O
+homologous	O
+to	O
+the	O
+Drosophila	B-GENE
+melanogaster	I-GENE
+segmentation	I-GENE
+gene	I-GENE
+runt	I-GENE
+.	O
+
+In	O
+human	O
+proliferative	O
+cells	O
+,	O
+the	O
+NADP	O
+-	O
+dependent	O
+ME	B-GENE
+activity	O
+is	O
+poorly	O
+expressed	O
+and	O
+barely	O
+inducible	O
+by	O
+thyroid	O
+hormones	O
+.	O
+
+Based	O
+on	O
+previous	O
+mapping	O
+of	O
+the	O
+G	B-GENE
+beta	I-GENE
+gamma	I-GENE
+binding	I-GENE
+region	I-GENE
+of	O
+beta	B-GENE
+ARK	I-GENE
+,	O
+and	O
+conserved	O
+residues	O
+within	O
+the	O
+PH	B-GENE
+domain	I-GENE
+,	O
+we	O
+have	O
+constructed	O
+a	O
+series	O
+of	O
+mutants	O
+in	O
+the	O
+carboxyl	O
+terminus	O
+of	O
+beta	B-GENE
+ARK	I-GENE
+in	O
+order	O
+to	O
+determine	O
+important	O
+residues	O
+involved	O
+in	O
+G	B-GENE
+beta	I-GENE
+gamma	I-GENE
+and	O
+PIP2	O
+binding	O
+.	O
+
+To	O
+dissect	O
+these	O
+mechanisms	O
+,	O
+wild	O
+-	O
+type	O
+and	O
+mutant	B-GENE
+Raf	I-GENE
+-	I-GENE
+1	I-GENE
+proteins	I-GENE
+were	O
+studied	O
+in	O
+an	O
+in	O
+vitro	O
+system	O
+with	O
+purified	O
+plasma	O
+membranes	O
+from	O
+v	B-GENE
+-	I-GENE
+Ras	I-GENE
+-	O
+and	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+-	O
+transformed	O
+cells	O
+(	O
+transformed	O
+membranes	O
+)	O
+.	O
+
+In	O
+CV	O
+-	O
+1	O
+cells	O
+,	O
+cotransfection	O
+of	O
+the	O
+retinoid	B-GENE
+and	I-GENE
+estrogen	I-GENE
+receptors	I-GENE
+led	O
+to	O
+mutual	O
+inhibition	O
+of	O
+the	O
+other	O
+'	O
+s	O
+activity	O
+,	O
+while	O
+an	O
+RA	O
+-	O
+dependent	O
+inhibition	O
+of	O
+ER	B-GENE
+activity	O
+was	O
+observed	O
+in	O
+breast	O
+cancer	O
+cells	O
+.	O
+
+D	O
+.	O
+
+It	O
+was	O
+proposed	O
+that	O
+the	O
+synthetase	O
+-	O
+related	O
+sequences	O
+of	O
+GCN2	B-GENE
+stimulate	O
+the	O
+activity	O
+of	O
+the	O
+kinase	O
+by	O
+interacting	O
+directly	O
+with	O
+uncharged	O
+tRNA	O
+that	O
+accumulates	O
+during	O
+amino	O
+acid	O
+limitation	O
+.	O
+
+However	O
+,	O
+unlike	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+the	O
+E1B	B-GENE
+19K	I-GENE
+proteins	I-GENE
+,	O
+which	O
+completely	O
+block	O
+apoptosis	O
+but	O
+not	O
+p53	B-GENE
+-	O
+dependent	O
+growth	O
+arrest	O
+,	O
+H	B-GENE
+-	I-GENE
+ras	I-GENE
+expression	O
+permitted	O
+DNA	O
+synthesis	O
+and	O
+cell	O
+proliferation	O
+in	O
+the	O
+presence	O
+of	O
+high	O
+levels	O
+of	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+p53	I-GENE
+.	O
+
+To	O
+compare	O
+the	O
+PAX3	B-GENE
+and	O
+putative	O
+PAX3	B-GENE
+-	O
+FKHR	B-GENE
+transactivation	O
+domains	O
+,	O
+we	O
+fused	O
+C	O
+-	O
+terminal	O
+test	O
+fragments	O
+to	O
+the	O
+heterologous	O
+GAL4	B-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+domain	I-GENE
+and	O
+tested	O
+activation	O
+of	O
+a	O
+reporter	O
+gene	O
+co	O
+-	O
+transfected	O
+into	O
+four	O
+cell	O
+types	O
+.	O
+
+All	O
+subjects	O
+were	O
+submitted	O
+to	O
+ECG	O
+and	O
+arterial	O
+blood	O
+pressure	O
+determination	O
+and	O
+were	O
+assayed	O
+for	O
+TSH	B-GENE
+,	O
+thyroid	O
+hormone	O
+,	O
+PRL	B-GENE
+,	O
+glucose	O
+,	O
+creatinine	O
+,	O
+nitrogen	O
+,	O
+glutamine	B-GENE
+transaminase	I-GENE
+,	O
+cholesterol	O
+and	O
+triglycerides	O
+plasma	O
+levels	O
+before	O
+therapy	O
+(	O
+T0	O
+)	O
+,	O
+after	O
+30	O
+treatment	O
+days	O
+(	O
+T30	O
+)	O
+and	O
+after	O
+a	O
+15	O
+days	O
+washout	O
+(	O
+T45	O
+)	O
+.	O
+
+Acute	O
+decrease	O
+in	O
+body	O
+temperature	O
+(	O
+TB	O
+)	O
+lowered	O
+PaCO2	O
+(	O
+32	O
+.	O
+5	O
+to	O
+14	O
+.	O
+5	O
+mmHg	O
+)	O
+and	O
+[	O
+HCO3	O
+-	O
+]	O
+a	O
+(	O
+24	O
+.	O
+20	O
+mEq	O
+/	O
+L	O
+to	O
+17	O
+.	O
+56	O
+mEq	O
+/	O
+L	O
+)	O
+,	O
+increased	O
+pHa	O
+(	O
+7	O
+.	O
+481	O
+to	O
+7	O
+.	O
+608	O
+)	O
+and	O
+diminished	O
+the	O
+[	O
+OH	O
+-	O
+]	O
+/	O
+[	O
+H	O
++	O
+]	O
+ratio	O
+,	O
+but	O
+had	O
+no	O
+significant	O
+effect	O
+on	O
+[	O
+SID	O
+]	O
+or	O
+[	O
+Atot	O
+]	O
+,	O
+although	O
+both	O
+total	O
+phosphorus	O
+[	O
+PT	O
+]	O
+and	O
+inorganic	O
+phosphate	O
+[	O
+Pi	O
+]	O
+increased	O
+.	O
+
+Hepatitis	O
+B	O
+vaccine	O
+:	O
+still	O
+has	O
+its	O
+problems	O
+.	O
+
+Basal	O
+promoter	O
+activity	O
+is	O
+enhanced	O
+by	O
+a	O
+functional	O
+M1	O
+domain	O
+in	O
+LHR	B-GENE
+-	O
+expressing	O
+mouse	O
+Leydig	O
+tumor	O
+cells	O
+(	O
+MLTC	O
+)	O
+but	O
+not	O
+in	O
+non	O
+-	O
+expressing	O
+CHO	O
+cells	O
+.	O
+
+For	O
+Al	O
+,	O
+the	O
+exposure	O
+to	O
+1	O
+.	O
+36	O
+mg	O
+/	O
+m3	O
+during	O
+the	O
+shift	O
+corresponded	O
+to	O
+a	O
+urinary	O
+concentration	O
+at	O
+the	O
+end	O
+of	O
+the	O
+shift	O
+of	O
+200	O
+microgram	O
+/	O
+g	O
+creatinine	O
+.	O
+
+Tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+alpha	I-GENE
+)	O
+,	O
+a	O
+proinflammatory	O
+cytokine	O
+,	O
+inhibits	O
+cAMP	O
+-	O
+stimulated	O
+testosterone	O
+production	O
+in	O
+mouse	O
+Leydig	O
+cells	O
+.	O
+
+The	O
+Drosophila	B-GENE
+insulin	I-GENE
+receptor	I-GENE
+homolog	I-GENE
+:	O
+a	O
+gene	O
+essential	O
+for	O
+embryonic	O
+development	O
+encodes	O
+two	O
+receptor	O
+isoforms	O
+with	O
+different	O
+signaling	O
+potential	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+RA	O
+and	O
+E1A	B-GENE
+induce	O
+phosphorylation	O
+of	O
+the	O
+E1A	B-GENE
+-	I-GENE
+associated	I-GENE
+300	I-GENE
+kDa	I-GENE
+protein	I-GENE
+(	O
+p300	B-GENE
+)	O
+during	O
+the	O
+differentiation	O
+of	O
+F9	O
+cells	O
+.	O
+
+The	O
+double	O
+-	O
+stranded	O
+RNA	O
+binding	O
+domain	O
+(	O
+dsRBD	O
+)	O
+is	O
+an	O
+approximately	O
+65	O
+amino	O
+acid	O
+motif	O
+that	O
+is	O
+found	O
+in	O
+a	O
+variety	O
+of	O
+proteins	O
+that	O
+interact	O
+with	O
+double	O
+-	O
+stranded	O
+(	O
+ds	O
+)	O
+RNA	O
+,	O
+such	O
+as	O
+Escherichia	O
+coli	O
+RNase	B-GENE
+III	I-GENE
+and	O
+the	O
+dsRNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+,	O
+PKR	B-GENE
+.	O
+
+SCA	B-GENE
+was	O
+resistant	O
+to	O
+inhibitors	O
+of	O
+serine	O
+,	O
+aspartyl	O
+,	O
+and	O
+metalloproteases	B-GENE
+,	O
+but	O
+it	O
+was	O
+sensitive	O
+to	O
+N	O
+-	O
+ethylmaleimide	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+potential	O
+activating	O
+phosphorylation	O
+sites	O
+found	O
+in	O
+NIMA	B-GENE
+,	O
+NIM	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+related	O
+protein	O
+kinases	O
+was	O
+performed	O
+on	O
+NIMA	B-GENE
+.	O
+
+However	O
+,	O
+a	O
+similar	O
+mutation	O
+of	O
+a	O
+leucine	O
+residue	O
+to	O
+arginine	O
+at	O
+position	O
+422	O
+showed	O
+no	O
+alteration	O
+of	O
+heterodimerization	O
+,	O
+DNA	O
+binding	O
+,	O
+or	O
+transcriptional	O
+activation	O
+.	O
+
+Expression	O
+of	O
+the	O
+CYP11A1	B-GENE
+gene	I-GENE
+is	O
+increased	O
+by	O
+hormones	O
+,	O
+such	O
+as	O
+adrenocorticotropin	B-GENE
+and	O
+luteinizing	B-GENE
+hormone	I-GENE
+,	O
+as	O
+well	O
+as	O
+by	O
+a	O
+number	O
+of	O
+growth	O
+factors	O
+,	O
+suggesting	O
+that	O
+its	O
+promoter	O
+may	O
+contain	O
+regulatory	O
+elements	O
+that	O
+respond	O
+to	O
+multiple	O
+signal	O
+transduction	O
+pathways	O
+.	O
+
+NH2	O
+-	O
+and	O
+COOH	O
+-	O
+terminal	O
+deletion	O
+analysis	O
+revealed	O
+that	O
+both	O
+the	O
+PH	B-GENE
+and	O
+putative	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factor	I-GENE
+domains	I-GENE
+are	O
+required	O
+,	O
+but	O
+the	O
+zinc	O
+butterfly	O
+is	O
+dispensable	O
+,	O
+for	O
+transformation	O
+.	O
+
+The	O
+objective	O
+of	O
+our	O
+study	O
+was	O
+to	O
+evaluate	O
+the	O
+age	O
+,	O
+sex	O
+,	O
+clinical	O
+conditions	O
+,	O
+family	O
+history	O
+,	O
+site	O
+,	O
+catheter	O
+association	O
+,	O
+means	O
+of	O
+radiologic	O
+evaluation	O
+,	O
+development	O
+of	O
+pulmonary	O
+involvement	O
+,	O
+prevalence	O
+of	O
+antithrombin	B-GENE
+III	I-GENE
+,	O
+protein	B-GENE
+C	I-GENE
+and	O
+protein	B-GENE
+S	I-GENE
+deficiencies	O
+,	O
+and	O
+lupus	O
+anticoagulants	O
+in	O
+children	O
+who	O
+suffered	O
+a	O
+thrombotic	O
+event	O
+.	O
+
+Harel	O
+,	O
+E	O
+.	O
+M	O
+.	O
+
+Radiotherapy	O
+and	O
+early	O
+orchiectomy	O
+in	O
+stage	O
+D1	O
+prostatic	O
+carcinoma	O
+
+Structural	O
+organization	O
+and	O
+developmental	O
+expression	O
+pattern	O
+of	O
+the	O
+mouse	B-GENE
+WD	I-GENE
+-	I-GENE
+repeat	I-GENE
+gene	I-GENE
+DMR	I-GENE
+-	I-GENE
+N9	I-GENE
+immediately	O
+upstream	O
+of	O
+the	O
+myotonic	B-GENE
+dystrophy	I-GENE
+locus	I-GENE
+.	O
+
+The	O
+ARX2	O
+procedure	O
+models	O
+the	O
+recorded	O
+signal	O
+as	O
+the	O
+sum	O
+of	O
+three	O
+signals	O
+:	O
+(	O
+a	O
+)	O
+the	O
+background	O
+EEG	O
+activity	O
+,	O
+modelled	O
+as	O
+an	O
+autoregressive	O
+process	O
+driven	O
+by	O
+a	O
+white	O
+noise	O
+;	O
+(	O
+b	O
+)	O
+a	O
+filtered	O
+version	O
+of	O
+a	O
+reference	O
+signal	O
+carrying	O
+the	O
+average	O
+information	O
+contained	O
+in	O
+each	O
+sweep	O
+;	O
+(	O
+c	O
+)	O
+a	O
+signal	O
+due	O
+to	O
+the	O
+ocular	O
+artefact	O
+propagation	O
+.	O
+
+The	O
+expression	O
+of	O
+the	O
+gene	O
+encoding	O
+the	O
+enzyme	O
+(	O
+CYP19	B-GENE
+)	O
+is	O
+regulated	O
+,	O
+in	O
+part	O
+,	O
+by	O
+tissue	O
+-	O
+specific	O
+promoters	O
+through	O
+the	O
+use	O
+of	O
+alternative	O
+-	O
+splicing	O
+mechanisms	O
+.	O
+
+CIITA	B-GENE
+mRNA	I-GENE
+is	O
+normally	O
+inducible	O
+by	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+in	O
+class	O
+II	O
+non	O
+-	O
+inducible	O
+,	O
+RB	O
+-	O
+defective	O
+lines	O
+,	O
+and	O
+in	O
+one	O
+line	O
+,	O
+re	O
+-	O
+expression	O
+of	O
+RB	B-GENE
+has	O
+no	O
+effect	O
+on	O
+CIITA	B-GENE
+mRNA	I-GENE
+induction	O
+levels	O
+.	O
+
+Consistent	O
+with	O
+the	O
+protein	O
+expression	O
+data	O
+,	O
+V	B-GENE
+beta	I-GENE
+8	I-GENE
+.	I-GENE
+3	I-GENE
+gene	I-GENE
+transcripts	I-GENE
+were	O
+found	O
+only	O
+in	O
+the	O
+transgenic	O
+lines	O
+with	O
+the	O
+wild	O
+-	O
+type	O
+promoter	O
+.	O
+
+One	O
+month	O
+after	O
+the	O
+DTaP	O
+booster	O
+vaccination	O
+,	O
+both	O
+groups	O
+had	O
+6	O
+-	O
+to	O
+40	O
+-	O
+fold	O
+increases	O
+in	O
+serum	O
+antibody	O
+concentrations	O
+to	O
+all	O
+antigens	O
+tested	O
+;	O
+the	O
+concentrations	O
+against	O
+the	O
+three	O
+pertussis	B-GENE
+antigens	I-GENE
+were	O
+higher	O
+in	O
+the	O
+DTaP	O
+-	O
+primed	O
+children	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+this	O
+amino	O
+-	O
+terminal	O
+determinant	O
+appears	O
+not	O
+to	O
+reside	O
+in	O
+the	O
+HSV	O
+-	O
+alpha	B-GENE
+TIF	I-GENE
+,	O
+which	O
+displays	O
+no	O
+independent	O
+amino	O
+-	O
+terminal	O
+activity	O
+.	O
+
+We	O
+also	O
+show	O
+that	O
+in	O
+fusions	O
+with	O
+the	O
+DNA	O
+binding	O
+domain	O
+of	O
+GAL4	B-GENE
+,	O
+full	O
+activity	O
+requires	O
+the	O
+entire	O
+BHV	B-GENE
+-	I-GENE
+alpha	I-GENE
+TIF	I-GENE
+,	O
+although	O
+both	O
+amino	O
+and	O
+carboxyl	O
+termini	O
+display	O
+some	O
+activity	O
+on	O
+their	O
+own	O
+.	O
+
+To	O
+investigate	O
+the	O
+potential	O
+role	O
+of	O
+SP1	B-GENE
+,	O
+we	O
+examined	O
+nuclear	O
+extracts	O
+from	O
+HCMV	O
+-	O
+infected	O
+cells	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+messenger	O
+RNAs	O
+encoding	O
+trans	O
+-	O
+sialidases	O
+containing	O
+the	O
+repeats	O
+are	O
+not	O
+present	O
+in	O
+epimastigotes	O
+but	O
+are	O
+abundant	O
+in	O
+trypomastigotes	O
+.	O
+
+From	O
+May	O
+1985	O
+to	O
+May	O
+1989	O
+,	O
+126	O
+necropsies	O
+were	O
+performed	O
+at	O
+the	O
+Sao	O
+Paulo	O
+City	O
+Morgue	O
+on	O
+cadavers	O
+of	O
+individuals	O
+AIDS	O
+victims	O
+whose	O
+unnatural	O
+deaths	O
+had	O
+prompted	O
+police	O
+investigations	O
+.	O
+
+A	O
+model	O
+with	O
+age	O
+and	O
+weight	O
+described	O
+the	O
+best	O
+fit	O
+for	O
+TBBMD	O
+,	O
+whereas	O
+age	O
+,	O
+weight	O
+,	O
+and	O
+height	O
+described	O
+the	O
+best	O
+fit	O
+for	O
+total	O
+body	O
+TBBMC	O
+.	O
+
+As	O
+retinoic	O
+acid	O
+and	O
+thyroid	O
+hormone	O
+are	O
+frequently	O
+involved	O
+in	O
+developmental	O
+regulatory	O
+processes	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+this	O
+element	O
+may	O
+be	O
+important	O
+in	O
+the	O
+process	O
+of	O
+islet	O
+cell	O
+differentiation	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+peptide	O
+sequences	O
+of	O
+the	O
+human	B-GENE
+lymphocyte	I-GENE
+-	I-GENE
+specific	I-GENE
+high	I-GENE
+mobility	I-GENE
+group	I-GENE
+(	I-GENE
+HMG	I-GENE
+)	I-GENE
+-	I-GENE
+box	I-GENE
+transcription	I-GENE
+factor	I-GENE
+TCF	I-GENE
+-	I-GENE
+1	I-GENE
+are	O
+determined	O
+by	O
+alternative	O
+splice	O
+mechanisms	O
+affecting	O
+the	O
+exons	O
+VIII	O
+to	O
+X	O
+.	O
+
+Thromboxane	O
+B2	O
+increased	O
+(	O
+97	O
++	O
+/	O
+-	O
+105	O
+versus	O
+40	O
++	O
+/	O
+-	O
+26	O
+pg	O
+/	O
+ml	O
+)	O
+and	O
+was	O
+significantly	O
+higher	O
+during	O
+heparin	O
+free	O
+hemodialysis	O
+than	O
+during	O
+hemodialysis	O
+with	O
+heparin	O
+(	O
+p	O
+=	O
+0	O
+.	O
+01	O
+,	O
+Wilcoxon	O
+matched	O
+pairs	O
+signed	O
+rank	O
+test	O
+)	O
+.	O
+
+To	O
+explore	O
+the	O
+mechanism	O
+of	O
+RSK	B-GENE
+activation	O
+,	O
+a	O
+cloned	O
+human	O
+RSK	B-GENE
+cDNA	O
+(	O
+RSK3	B-GENE
+)	O
+was	O
+used	O
+to	O
+generate	O
+and	O
+characterize	O
+several	O
+site	O
+-	O
+directed	O
+RSK	B-GENE
+mutants	I-GENE
+;	O
+K91A	O
+(	O
+N	O
+-	O
+Lys	O
+,	O
+NH2	O
+-	O
+terminal	O
+ATP	O
+-	O
+binding	O
+mutant	O
+)	O
+,	O
+K444A	O
+(	O
+C	O
+-	O
+Lys	O
+,	O
+COOH	O
+-	O
+terminal	O
+ATP	O
+-	O
+binding	O
+mutant	O
+)	O
+,	O
+N	O
+/	O
+C	O
+-	O
+Lys	O
+(	O
+double	O
+ATP	O
+-	O
+binding	O
+mutant	O
+)	O
+T570A	O
+(	O
+C	O
+-	O
+Thr	O
+,	O
+mutant	O
+of	O
+the	O
+putative	O
+MAPK	B-GENE
+phosphorylation	O
+site	O
+in	O
+subdomain	O
+VIII	O
+of	O
+the	O
+C	O
+-	O
+domain	O
+)	O
+,	O
+S218A	O
+(	O
+N	O
+-	O
+Ser	O
+,	O
+mutant	O
+of	O
+the	O
+corresponding	O
+NH2	O
+-	O
+terminal	O
+residue	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+both	O
+C	O
+-	O
+Lys	O
+and	O
+C	O
+-	O
+Thr	O
+retained	O
+high	O
+levels	O
+of	O
+kinase	O
+activity	O
+and	O
+were	O
+capable	O
+of	O
+responding	O
+to	O
+stimulation	O
+.	O
+
+Conversely	O
+,	O
+treatment	O
+of	O
+human	B-GENE
+protein	I-GENE
+-	I-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+alpha	I-GENE
+-	O
+overexpressing	O
+cells	O
+with	O
+phenylarsine	O
+oxide	O
+led	O
+to	O
+a	O
+loss	O
+of	O
+the	O
+constitutive	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+activity	O
+.	O
+
+A	O
+TATA	O
+-	O
+less	O
+promoter	O
+containing	O
+binding	O
+sites	O
+for	O
+ubiquitous	O
+transcription	O
+factors	O
+mediates	O
+cell	O
+type	O
+-	O
+specific	O
+regulation	O
+of	O
+the	O
+gene	O
+for	O
+transcription	B-GENE
+enhancer	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+TEF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+Since	O
+electrical	O
+stimulation	O
+of	O
+neurones	O
+may	O
+activate	O
+not	O
+only	O
+cell	O
+bodies	O
+but	O
+also	O
+neuronal	O
+fibres	O
+,	O
+this	O
+study	O
+aimed	O
+to	O
+test	O
+a	O
+selectively	O
+cholinergic	O
+neurochemical	O
+stimulation	O
+of	O
+the	O
+rat	O
+substantia	O
+innominata	O
+(	O
+SI	O
+)	O
+by	O
+the	O
+local	O
+microinjection	O
+of	O
+carbachol	O
+;	O
+the	O
+effects	O
+of	O
+this	O
+acetylcholine	O
+agonist	O
+were	O
+compared	O
+with	O
+glutamate	O
+.	O
+
+We	O
+purified	O
+both	O
+proteins	O
+from	O
+human	O
+platelet	O
+membranes	O
+using	O
+DEAE	O
+-	O
+Sepharose	O
+chromatography	O
+followed	O
+by	O
+mAb	B-GENE
+F11	I-GENE
+affinity	O
+chromatography	O
+.	O
+
+The	O
+homeobox	B-GENE
+gene	I-GENE
+ATK1	I-GENE
+of	O
+Arabidopsis	O
+thaliana	O
+is	O
+expressed	O
+in	O
+the	O
+shoot	O
+apex	O
+of	O
+the	O
+seedling	O
+and	O
+in	O
+flowers	O
+and	O
+inflorescence	O
+stems	O
+of	O
+mature	O
+plants	O
+.	O
+
+The	O
+most	O
+likely	O
+explanation	O
+for	O
+this	O
+is	O
+that	O
+gold	O
+principally	O
+accumulates	O
+in	O
+the	O
+Kupffer	O
+cells	O
+and	O
+renal	O
+cortex	O
+and	O
+these	O
+cells	O
+do	O
+not	O
+express	O
+Type	B-GENE
+I	I-GENE
+deiodinase	I-GENE
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+different	O
+models	O
+of	O
+intestinal	O
+ischemia	O
+have	O
+different	O
+cytokine	O
+profiles	O
+and	O
+that	O
+the	O
+early	O
+TNF	B-GENE
+response	O
+associated	O
+with	O
+SMA	O
+occlusion	O
+model	O
+is	O
+primarily	O
+due	O
+to	O
+the	O
+laparotomy	O
+.	O
+
+Our	O
+evidence	O
+derives	O
+from	O
+three	O
+principal	O
+observations	O
+:	O
+1	O
+)	O
+a	O
+transfection	O
+construct	O
+containing	O
+only	O
+122	O
+nucleotides	O
+(	O
+nt	O
+)	O
+of	O
+promoter	O
+1	O
+and	O
+328	O
+nt	O
+of	O
+the	O
+5	O
+'	O
+-	O
+UTR	O
+retained	O
+full	O
+PGE2	O
+-	O
+stimulated	O
+reporter	O
+expression	O
+;	O
+2	O
+)	O
+maximal	O
+PGE2	O
+-	O
+driven	O
+reporter	O
+expression	O
+required	O
+the	O
+presence	O
+of	O
+nt	O
+196	O
+to	O
+328	O
+of	O
+exon	O
+1	O
+when	O
+tested	O
+within	O
+the	O
+context	O
+of	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+promoter	I-GENE
+1	I-GENE
+;	O
+3	O
+)	O
+cotransfection	O
+of	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+promoter	I-GENE
+-	O
+luciferase	B-GENE
+-	O
+reporter	O
+constructs	O
+with	O
+a	O
+plasmid	O
+encoding	O
+the	O
+alpha	O
+-	O
+isoform	O
+of	O
+the	O
+catalytic	O
+subunit	O
+of	O
+murine	B-GENE
+cAMP	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+PKA	B-GENE
+)	O
+produced	O
+results	O
+comparable	O
+to	O
+those	O
+seen	O
+with	O
+PGE2	O
+treatment	O
+,	O
+whereas	O
+cotransfection	O
+with	O
+a	O
+plasmid	O
+encoding	O
+a	O
+mutant	O
+regulatory	O
+subunit	O
+of	O
+PKA	B-GENE
+that	O
+cannot	O
+bind	O
+cAMP	O
+blocked	O
+PGE2	O
+-	O
+induced	O
+reporter	O
+expression	O
+.	O
+
+The	O
+changes	O
+after	O
+treatment	O
+were	O
+observed	O
+chiefly	O
+by	O
+electromyography	O
+while	O
+sensory	O
+and	O
+motor	O
+improvement	O
+were	O
+also	O
+recorded	O
+as	O
+auxiliary	O
+indicators	O
+.	O
+
+Band	O
+-	O
+shift	O
+assays	O
+and	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+experiments	O
+using	O
+purified	O
+42	O
+kDa	O
+repressor	O
+isoform	O
+confirmed	O
+that	O
+CIRs	B-GENE
+5	I-GENE
+and	I-GENE
+6	I-GENE
+were	O
+indeed	O
+the	O
+targets	O
+for	O
+binding	O
+of	O
+this	O
+protein	O
+.	O
+
+Retransformation	O
+of	O
+uvsH77	B-GENE
+mutants	I-GENE
+with	O
+the	O
+rescued	O
+cosmids	O
+from	O
+the	O
+MMS	O
+-	O
+resistant	O
+transformants	O
+resulted	O
+in	O
+restoration	O
+of	O
+both	O
+UV	O
+and	O
+MMS	O
+resistance	O
+to	O
+wild	O
+-	O
+type	O
+levels	O
+.	O
+
+Furthermore	O
+,	O
+this	O
+element	O
+confers	O
+p53	B-GENE
+induction	O
+to	O
+the	O
+otherwise	O
+nonresponsive	O
+adenovirus	O
+major	O
+late	O
+promoter	O
+.	O
+
+In	O
+flies	O
+,	O
+the	O
+dShc	B-GENE
+protein	I-GENE
+physically	O
+associates	O
+with	O
+the	O
+activated	O
+Drosophila	B-GENE
+epidermal	I-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+homolog	I-GENE
+(	O
+DER	B-GENE
+)	O
+and	O
+is	O
+inducibly	O
+phosphorylated	O
+on	O
+tyrosine	O
+by	O
+DER	B-GENE
+.	O
+
+A	O
+potential	O
+binding	O
+site	O
+for	O
+the	O
+dShc	B-GENE
+PTB	O
+domain	O
+is	O
+located	O
+at	O
+Tyr	O
+-	O
+1228	O
+of	O
+DER	B-GENE
+.	O
+
+A	O
+Drosophila	B-GENE
+shc	I-GENE
+gene	I-GENE
+product	I-GENE
+is	O
+implicated	O
+in	O
+signaling	O
+by	O
+the	O
+DER	B-GENE
+receptor	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+.	O
+
+This	O
+inhibition	O
+can	O
+be	O
+overcome	O
+by	O
+mutating	O
+either	O
+the	O
+exon	O
+'	O
+s	O
+5	O
+'	O
+or	O
+3	O
+'	O
+splice	O
+site	O
+to	O
+make	O
+it	O
+correspond	O
+more	O
+closely	O
+to	O
+the	O
+relevant	O
+consensus	O
+sequence	O
+.	O
+
+Biochemical	O
+analysis	O
+shows	O
+that	O
+Ssm1p	B-GENE
+is	O
+a	O
+structural	O
+protein	O
+that	O
+forms	O
+part	O
+of	O
+the	O
+largest	O
+60S	B-GENE
+ribosomal	I-GENE
+subunit	I-GENE
+,	O
+which	O
+does	O
+not	O
+exist	O
+in	O
+a	O
+pool	O
+of	O
+free	O
+proteins	O
+.	O
+
+In	O
+wild	O
+-	O
+type	O
+cells	O
+,	O
+SSM1b	B-GENE
+transcripts	I-GENE
+accumulate	O
+to	O
+twice	O
+the	O
+level	O
+of	O
+SSM1a	B-GENE
+transcripts	I-GENE
+,	O
+suggesting	O
+that	O
+SSM1b	B-GENE
+is	O
+responsible	O
+for	O
+the	O
+majority	O
+of	O
+the	O
+Ssm1p	B-GENE
+pool	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+revealed	O
+the	O
+expression	O
+of	O
+LIMK	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+predominantly	O
+in	O
+the	O
+brain	O
+and	O
+the	O
+expression	O
+of	O
+LIMK	B-GENE
+-	I-GENE
+2	I-GENE
+mRNA	I-GENE
+in	O
+various	O
+tissues	O
+in	O
+the	O
+rat	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+this	O
+anatomic	O
+concept	O
+,	O
+the	O
+brachioplasty	O
+procedure	O
+was	O
+modified	O
+to	O
+provide	O
+secure	O
+anchoring	O
+of	O
+the	O
+arm	O
+flap	O
+to	O
+the	O
+axillary	O
+fascia	O
+along	O
+with	O
+strong	O
+superficial	O
+fascial	O
+system	O
+repair	O
+of	O
+incisions	O
+,	O
+reducing	O
+the	O
+risk	O
+of	O
+widening	O
+or	O
+migration	O
+of	O
+scars	O
+and	O
+unnatural	O
+contours	O
+.	O
+
+Furthermore	O
+,	O
+microinjection	O
+of	O
+dominant	O
+negative	O
+forms	O
+of	O
+Rac	B-GENE
+and	O
+Cdc42	B-GENE
+or	O
+of	O
+the	O
+Rho	B-GENE
+inhibitor	O
+C3	B-GENE
+transferase	I-GENE
+blocked	O
+serum	O
+-	O
+induced	O
+DNA	O
+synthesis	O
+.	O
+
+INF	B-GENE
+-	I-GENE
+alpha	I-GENE
+therapy	O
+has	O
+been	O
+a	O
+major	O
+development	O
+in	O
+the	O
+treatment	O
+of	O
+CML	O
+.	O
+
+A	O
+series	O
+of	O
+amino	O
+terminal	O
+deletion	O
+mutants	O
+(	O
+d10	O
+,	O
+d20	O
+,	O
+d27	O
+,	O
+d31	O
+,	O
+d40	O
+,	O
+d44	O
+,	O
+and	O
+d73	O
+)	O
+were	O
+compared	O
+for	O
+processing	O
+,	O
+cell	O
+surface	O
+expression	O
+,	O
+and	O
+maintenance	O
+of	O
+their	O
+biological	O
+attributes	O
+by	O
+recombinant	O
+expression	O
+of	O
+mutant	O
+genes	O
+using	O
+a	O
+plasmid	O
+vector	O
+(	O
+pcDL	O
+-	O
+SR	O
+alpha	O
+-	O
+296	O
+)	O
+in	O
+CV	O
+-	O
+1	O
+and	O
+HeLa	O
+cells	O
+.	O
+
+Intrathecal	O
+acetyl	B-GENE
+cholinesterase	I-GENE
+inhibitors	O
+produce	O
+analgesia	O
+that	O
+is	O
+synergistic	O
+with	O
+morphine	O
+and	O
+clonidine	O
+in	O
+rats	O
+.	O
+
+After	O
+determining	O
+isoflurane	O
+MAC	O
+in	O
+triplicate	O
+,	O
+birds	O
+were	O
+given	O
+a	O
+mu	O
+-	O
+opioid	O
+agonist	O
+(	O
+morphine	O
+,	O
+n	O
+=	O
+9	O
+)	O
+or	O
+a	O
+kappa	O
+-	O
+opioid	O
+agonist	O
+(	O
+U50488H	O
+,	O
+n	O
+=	O
+9	O
+)	O
+.	O
+
+Max	B-GENE
+was	O
+constantly	O
+transcribed	O
+at	O
+a	O
+relatively	O
+low	O
+level	O
+during	O
+cell	O
+cycle	O
+progression	O
+.	O
+
+The	O
+yeast	O
+enzyme	O
+was	O
+6	O
+-	O
+fold	O
+slower	O
+than	O
+the	O
+mammalian	O
+enzymes	O
+,	O
+which	O
+made	O
+it	O
+amenable	O
+to	O
+pre	O
+-	O
+steady	O
+-	O
+state	O
+stopped	O
+-	O
+flow	O
+spectroscopic	O
+kinetic	O
+analysis	O
+at	O
+30	O
+degrees	O
+C	O
+and	O
+pH	O
+6	O
+.	O
+0	O
+.	O
+
+Key	O
+areas	O
+of	O
+the	O
+selection	O
+process	O
+including	O
+medical	O
+and	O
+surgical	O
+alternatives	O
+to	O
+transplantation	O
+,	O
+the	O
+composition	O
+of	O
+the	O
+transplant	O
+work	O
+-	O
+up	O
+,	O
+specific	O
+inclusion	O
+criteria	O
+as	O
+well	O
+as	O
+specific	O
+psychosocial	O
+factors	O
+and	O
+specific	O
+disease	O
+etiologies	O
+and	O
+co	O
+-	O
+morbidities	O
+that	O
+might	O
+represent	O
+contraindications	O
+were	O
+extensively	O
+reviewed	O
+.	O
+
+In	O
+both	O
+shoots	O
+and	O
+roots	O
+,	O
+GT	B-GENE
+-	I-GENE
+2	I-GENE
+protein	I-GENE
+is	O
+undetectable	O
+in	O
+meristematic	O
+tissue	O
+but	O
+becomes	O
+expressed	O
+at	O
+later	O
+stages	O
+of	O
+cellular	O
+development	O
+,	O
+consistent	O
+with	O
+a	O
+role	O
+in	O
+contributing	O
+to	O
+the	O
+pattern	O
+of	O
+phytochrome	B-GENE
+A	I-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Comparative	O
+DNA	O
+sequence	O
+analysis	O
+showed	O
+the	O
+Genethon	O
+microsatellite	B-GENE
+D19S596	I-GENE
+lies	O
+2	O
+.	O
+2	O
+kb	O
+downstream	O
+of	O
+the	O
+coding	O
+region	O
+of	O
+FUT1	B-GENE
+,	O
+indicating	O
+that	O
+the	O
+cluster	O
+comprising	O
+the	O
+closely	O
+linked	O
+FUT1	B-GENE
+and	O
+FUT2	B-GENE
+genes	I-GENE
+is	O
+located	O
+4	O
+cM	O
+distal	O
+to	O
+D19S412	B-GENE
+(	O
+lod	O
+score	O
+13	O
+.	O
+7	O
+)	O
+and	O
+9	O
+cM	O
+proximal	O
+to	O
+D19S571	B-GENE
+(	O
+lod	O
+score	O
+11	O
+.	O
+7	O
+)	O
+.	O
+
+We	O
+conclude	O
+that	O
+transcription	O
+activation	O
+by	O
+LEF	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+vitro	O
+is	O
+a	O
+chromatin	O
+-	O
+dependent	O
+process	O
+that	O
+requires	O
+a	O
+functional	O
+trans	O
+-	O
+activation	O
+domain	O
+in	O
+addition	O
+to	O
+the	O
+HMG	B-GENE
+domain	I-GENE
+.	O
+
+TH	B-GENE
+-	O
+SH3	B-GENE
+binding	O
+in	O
+vitro	O
+is	O
+abolished	O
+by	O
+specific	O
+,	O
+single	O
+amino	O
+acid	O
+substitutions	O
+within	O
+the	O
+Btk	B-GENE
+TH	B-GENE
+domain	I-GENE
+or	O
+the	O
+Fyn	B-GENE
+SH3	B-GENE
+domain	I-GENE
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+K	B-GENE
+-	I-GENE
+glypican	I-GENE
+is	O
+a	O
+novel	O
+GPI	B-GENE
+-	I-GENE
+anchored	I-GENE
+HSPG	I-GENE
+involved	O
+in	O
+embryonic	O
+development	O
+.	O
+
+Protein	B-GENE
+S	I-GENE
+levels	O
+were	O
+virtually	O
+undetectable	O
+at	O
+the	O
+time	O
+of	O
+admission	O
+and	O
+failed	O
+to	O
+respond	O
+to	O
+infusions	O
+of	O
+fresh	O
+frozen	O
+plasma	O
+,	O
+despite	O
+correction	O
+of	O
+other	O
+procoagulant	O
+and	O
+anticoagulant	O
+factors	O
+.	O
+
+The	O
+test	O
+was	O
+not	O
+performed	O
+in	O
+3923	O
+patients	O
+because	O
+of	O
+contraindications	O
+.	O
+
+The	O
+ubiquitous	O
+transcription	O
+factor	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+forms	O
+complexes	O
+with	O
+an	O
+octamer	O
+motif	O
+present	O
+within	O
+FPIV	O
+by	O
+gel	O
+shift	O
+analysis	O
+with	O
+liver	O
+and	O
+kidney	O
+extracts	O
+,	O
+making	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+an	O
+intriguing	O
+candidate	O
+for	O
+partnership	O
+in	O
+androgen	O
+regulation	O
+.	O
+
+We	O
+used	O
+deletion	O
+analysis	O
+and	O
+transfection	O
+assays	O
+with	O
+reporter	O
+gene	O
+constructs	O
+to	O
+examine	O
+the	O
+transcription	O
+control	O
+elements	O
+in	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+EpoR	I-GENE
+gene	I-GENE
+.	O
+
+Incubation	O
+of	O
+the	O
+purified	O
+fusion	O
+proteins	O
+with	O
+[	O
+gamma	O
+-	O
+32P	O
+]	O
+ATP	O
+in	O
+an	O
+in	O
+vitro	O
+assay	O
+showed	O
+that	O
+both	O
+proteins	O
+were	O
+capable	O
+of	O
+autophosphorylation	O
+.	O
+
+The	O
+character	O
+of	O
+specific	O
+immune	O
+response	O
+in	O
+101	O
+immunized	O
+children	O
+and	O
+in	O
+12	O
+adults	O
+belonging	O
+to	O
+a	O
+high	O
+risk	O
+group	O
+with	O
+respect	O
+to	O
+VHB	O
+.	O
+
+After	O
+nadolol	O
+,	O
+heart	O
+rate	O
+decreased	O
+(	O
+-	O
+22	O
++	O
+/	O
+-	O
+8	O
+%	O
+)	O
+,	O
+and	O
+so	O
+did	O
+PBV	O
+and	O
+PBF	O
+(	O
+8	O
+.	O
+8	O
++	O
+/	O
+-	O
+3	O
+.	O
+4	O
+vs	O
+.	O
+
+Adrenergic	O
+system	O
+activation	O
+,	O
+indicated	O
+by	O
+metanephrine	O
+/	O
+epinephrine	O
+ratio	O
+,	O
+increased	O
+with	O
+time	O
+in	O
+losing	O
+males	O
+,	O
+except	O
+that	O
+after	O
+one	O
+month	O
+of	O
+cohabitation	O
+,	O
+turnover	O
+returned	O
+to	O
+levels	O
+that	O
+equaled	O
+those	O
+of	O
+control	O
+animals	O
+.	O
+
+Transabdominal	O
+repair	O
+of	O
+type	O
+IV	O
+thoraco	O
+-	O
+abdominal	O
+aortic	O
+aneurysms	O
+.	O
+
+A	O
+.	O
+
+Primer	O
+extension	O
+and	O
+cDNA	O
+cloning	O
+were	O
+used	O
+to	O
+isolate	O
+the	O
+complete	O
+5	O
+'	O
+end	O
+of	O
+the	O
+Nramp1	B-GENE
+mRNA	I-GENE
+.	O
+
+Primer	O
+extension	O
+and	O
+S1	B-GENE
+nuclease	I-GENE
+mapping	O
+experiments	O
+were	O
+used	O
+to	O
+locate	O
+the	O
+transcription	O
+initiation	O
+site	O
+of	O
+Nramp1	B-GENE
+and	O
+revealed	O
+the	O
+presence	O
+of	O
+one	O
+major	O
+and	O
+several	O
+minor	O
+initiation	O
+sites	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+CD69	B-GENE
+gene	I-GENE
+revealed	O
+the	O
+presence	O
+of	O
+a	O
+potential	O
+TATA	O
+element	O
+30	O
+base	O
+pairs	O
+upstream	O
+of	O
+the	O
+major	O
+transcription	O
+initiation	O
+site	O
+and	O
+several	O
+putative	O
+binding	O
+sequences	O
+for	O
+inducible	O
+transcription	O
+factors	O
+(	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+,	O
+Egr	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+which	O
+might	O
+mediate	O
+the	O
+inducible	O
+expression	O
+of	O
+this	O
+gene	O
+.	O
+
+The	O
+plasmin	B-GENE
+-	I-GENE
+derived	I-GENE
+D	I-GENE
+(	I-GENE
+approximately	I-GENE
+105	I-GENE
+-	I-GENE
+kDa	I-GENE
+)	I-GENE
+product	I-GENE
+,	O
+however	O
+,	O
+could	O
+be	O
+cross	O
+-	O
+linked	O
+into	O
+DD	O
+dimers	O
+.	O
+
+All	O
+clinical	O
+isolates	O
+were	O
+concomitantly	O
+tested	O
+by	O
+disk	O
+diffusion	O
+and	O
+agar	O
+dilution	O
+procedures	O
+as	O
+outlined	O
+by	O
+the	O
+National	O
+Committee	O
+for	O
+Clinical	O
+Laboratory	O
+Standards	O
+.	O
+
+IgE	B-GENE
+levels	O
+showed	O
+higher	O
+values	O
+compared	O
+to	O
+normal	O
+individuals	O
+and	O
+IgE	B-GENE
+levels	O
+were	O
+higher	O
+in	O
+children	O
+groups	O
+than	O
+in	O
+adults	O
+regardless	O
+of	O
+the	O
+intensity	O
+of	O
+infection	O
+.	O
+
+Tissue	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+tmy	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+was	O
+determined	O
+by	O
+microinjection	O
+of	O
+a	O
+promoter	B-GENE
+/	I-GENE
+lacZ	I-GENE
+fusion	I-GENE
+gene	I-GENE
+and	O
+with	O
+immunohistochemistry	O
+by	O
+using	O
+affinity	O
+-	O
+purified	O
+tissue	B-GENE
+-	I-GENE
+specific	I-GENE
+anti	I-GENE
+-	I-GENE
+tropomyosins	I-GENE
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+chloroplast	O
+(	O
+cp	O
+)	O
+DNA	O
+from	O
+maize	O
+(	O
+Zea	O
+mays	O
+)	O
+has	O
+been	O
+completed	O
+.	O
+
+Investigation	O
+of	O
+the	O
+control	O
+of	O
+coronavirus	O
+subgenomic	O
+mRNA	O
+transcription	O
+by	O
+using	O
+T7	O
+-	O
+generated	O
+negative	O
+-	O
+sense	O
+RNA	O
+transcripts	O
+.	O
+
+Initiation	O
+of	O
+translation	O
+of	O
+the	O
+human	O
+hepatitis	O
+C	O
+virus	O
+(	O
+HCV	O
+)	O
+RNA	O
+genome	O
+occurs	O
+by	O
+internal	O
+ribosome	O
+entry	O
+into	O
+the	O
+5	O
+'	O
+noncoding	O
+region	O
+(	O
+5	O
+'	O
+NCR	O
+)	O
+in	O
+a	O
+cap	O
+-	O
+independent	O
+manner	O
+.	O
+
+Mean	O
+longitudinal	O
+extension	O
+of	O
+the	O
+epidural	O
+lesion	O
+was	O
+2	O
+.	O
+6	O
+vertebral	O
+segments	O
+.	O
+
+The	O
+association	O
+of	O
+p255	B-GENE
+with	O
+splicing	O
+complexes	O
+is	O
+suggested	O
+by	O
+the	O
+finding	O
+that	O
+mAb	B-GENE
+CC3	I-GENE
+can	O
+inhibit	O
+in	O
+vitro	O
+splicing	O
+and	O
+immunoprecipitate	O
+pre	O
+-	O
+messenger	O
+RNA	O
+and	O
+splicing	O
+products	O
+.	O
+
+L	O
+-	O
+735	O
+,	O
+524	O
+free	O
+base	O
+or	O
+sulfate	O
+salt	O
+was	O
+administered	O
+orally	O
+as	O
+suspension	O
+,	O
+solution	O
+or	O
+in	O
+solid	O
+dosage	O
+forms	O
+to	O
+fasted	O
+or	O
+fed	O
+Beagle	O
+dogs	O
+.	O
+
+Doppler	O
+ultrasound	O
+studies	O
+of	O
+long	O
+-	O
+term	O
+follow	O
+-	O
+up	O
+of	O
+children	O
+with	O
+hemolytic	O
+-	O
+uremic	O
+syndrome	O
+
+Thus	O
+,	O
+endemic	O
+cumlations	O
+of	O
+hepatitis	O
+A	O
+diseases	O
+are	O
+possible	O
+.	O
+
+(	O
+1991	O
+)	O
+.	O
+
+The	O
+properties	O
+of	O
+the	O
+phi	O
+29	O
+SSB	B-GENE
+-	I-GENE
+ssDNA	I-GENE
+complex	O
+are	O
+described	O
+.	O
+
+This	O
+shows	O
+that	O
+the	O
+characteristically	O
+diffuse	O
+banding	O
+pattern	O
+of	O
+plant	O
+nuclear	O
+proteins	O
+interacting	O
+with	O
+the	O
+G	O
+-	O
+box	O
+is	O
+also	O
+observed	O
+in	O
+a	O
+binding	O
+assay	O
+using	O
+only	O
+one	O
+recombinant	B-GENE
+GBF	I-GENE
+.	O
+
+We	O
+studied	O
+120	O
+male	O
+and	O
+42	O
+female	O
+patients	O
+with	O
+early	O
+CAD	O
+who	O
+were	O
+unrelated	O
+to	O
+each	O
+other	O
+but	O
+were	O
+from	O
+families	O
+in	O
+which	O
+at	O
+least	O
+one	O
+other	O
+sibling	O
+had	O
+early	O
+CAD	O
+.	O
+
+The	O
+physical	O
+linkage	O
+of	O
+the	O
+FHR2	B-GENE
+and	O
+the	O
+factor	B-GENE
+H	I-GENE
+genes	I-GENE
+provides	O
+additional	O
+evidence	O
+for	O
+a	O
+close	O
+relatedness	O
+of	O
+complement	B-GENE
+factor	I-GENE
+H	I-GENE
+and	O
+the	O
+factor	B-GENE
+H	I-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+.	O
+
+Genomic	O
+structure	O
+and	O
+chromosomal	O
+location	O
+of	O
+the	O
+mouse	B-GENE
+pre	I-GENE
+-	I-GENE
+T	I-GENE
+-	I-GENE
+cell	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+third	O
+domain	O
+had	O
+the	O
+motif	O
+of	O
+a	O
+cAMP	O
+response	O
+element	O
+(	O
+CRE	O
+)	O
+.	O
+
+The	O
+tyrosine	O
+-	O
+phosphorylated	O
+state	O
+of	O
+CAK	B-GENE
+beta	I-GENE
+was	O
+not	O
+reduced	O
+on	O
+trypsinization	O
+,	O
+nor	O
+enhanced	O
+in	O
+response	O
+to	O
+plating	O
+3Y1	O
+cells	O
+onto	O
+fibronectin	B-GENE
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+while	O
+many	O
+muscle	O
+gene	O
+E	O
+-	O
+boxes	O
+are	O
+capable	O
+of	O
+binding	O
+the	O
+previously	O
+characterized	O
+spectrum	O
+of	O
+MDF	B-GENE
+/	I-GENE
+bH	I-GENE
+-	I-GENE
+L	I-GENE
+-	I-GENE
+H	I-GENE
+heterodimers	I-GENE
+in	O
+vitro	O
+,	O
+MCK	B-GENE
+-	I-GENE
+L	I-GENE
+type	O
+E	O
+-	O
+boxes	O
+probably	O
+bind	O
+qualitatively	O
+different	O
+factors	O
+in	O
+vivo	O
+.	O
+
+A	O
+single	O
+-	O
+case	O
+experimental	O
+ABAB	O
+multiple	O
+baseline	O
+design	O
+was	O
+employed	O
+to	O
+test	O
+for	O
+treatment	O
+effectiveness	O
+.	O
+
+These	O
+clones	O
+were	O
+found	O
+to	O
+share	O
+a	O
+common	O
+domain	O
+encoded	O
+by	O
+p	O
+(	O
+CA	O
+)	O
+n	O
+repeats	O
+;	O
+a	O
+simple	O
+sequence	O
+length	O
+polymorphism	O
+(	O
+SSLP	O
+)	O
+.	O
+
+In	O
+one	O
+glioblastoma	O
+cell	O
+line	O
+,	O
+a	O
+Shc	B-GENE
+-	O
+associated	O
+p190	B-GENE
+was	O
+identified	O
+as	O
+the	O
+activated	O
+PDGFR	B-GENE
+.	O
+
+The	O
+serum	O
+concentration	O
+of	O
+iP	O
+before	O
+dialysis	O
+(	O
+HD	O
+)	O
+was	O
+on	O
+average	O
+3	O
+.	O
+06	O
+(	O
++	O
+/	O
+-	O
+0	O
+.	O
+81	O
+)	O
+mmol	O
+/	O
+l	O
+and	O
+D	O
+was	O
+on	O
+average	O
+55	O
+.	O
+6	O
+(	O
++	O
+/	O
+-	O
+10	O
+.	O
+0	O
+)	O
+mmol	O
+.	O
+
+A	O
+significant	O
+correlation	O
+between	O
+a	O
+number	O
+of	O
+functional	O
+parameters	O
+of	O
+gastric	O
+secretion	O
+,	O
+incretion	O
+and	O
+histological	O
+changes	O
+of	O
+gastric	O
+mucosa	O
+was	O
+found	O
+in	O
+patients	O
+with	O
+chronic	O
+gastritis	O
+.	O
+
+The	O
+TAF	O
+factor	O
+appears	O
+to	O
+be	O
+particularly	O
+significant	O
+in	O
+OCD	O
+.	O
+
+RNase	B-GENE
+protection	O
+analyses	O
+indicate	O
+that	O
+either	O
+61	B-GENE
+-	I-GENE
+kDa	I-GENE
+CaM	I-GENE
+PDE	I-GENE
+mRNA	I-GENE
+or	O
+structurally	O
+related	O
+transcripts	O
+encoding	O
+different	O
+CaM	B-GENE
+PDE	I-GENE
+isoforms	I-GENE
+are	O
+expressed	O
+in	O
+a	O
+tissue	O
+-	O
+specific	O
+manner	O
+.	O
+
+Little	O
+or	O
+no	O
+protection	O
+was	O
+detected	O
+using	O
+adrenal	O
+cortex	O
+,	O
+adrenal	O
+medulla	O
+,	O
+liver	O
+,	O
+kidney	O
+cortex	O
+,	O
+spleen	O
+,	O
+or	O
+T	O
+-	O
+lymphocyte	O
+total	O
+RNA	O
+.	O
+
+The	O
+PDGFR	B-GENE
+mutants	I-GENE
+that	O
+failed	O
+to	O
+associate	O
+with	O
+PLC	B-GENE
+gamma	I-GENE
+were	O
+not	O
+able	O
+to	O
+mediate	O
+the	O
+PDGF	B-GENE
+-	O
+dependent	O
+production	O
+of	O
+inositol	O
+phosphates	O
+.	O
+
+We	O
+found	O
+a	O
+direct	O
+correlation	O
+between	O
+the	O
+levels	O
+of	O
+transcription	O
+of	O
+the	O
+acc	B-GENE
+genes	I-GENE
+and	O
+the	O
+rate	O
+of	O
+cellular	O
+growth	O
+.	O
+
+The	O
+hybridizing	O
+clone	O
+of	O
+V	O
+.	O
+vulnificus	O
+chromosomal	O
+DNA	O
+complemented	O
+a	O
+V	B-GENE
+.	I-GENE
+cholerae	I-GENE
+fur	I-GENE
+mutant	I-GENE
+.	O
+
+We	O
+generated	O
+transformed	O
+B	O
+lymphoblast	O
+cell	O
+lines	O
+from	O
+controls	O
+,	O
+from	O
+four	O
+patients	O
+with	O
+p47	B-GENE
+-	O
+phox	B-GENE
+-	O
+deficient	O
+chronic	O
+granulomatous	O
+disease	O
+,	O
+and	O
+from	O
+three	O
+parents	O
+.	O
+
+RNase	B-GENE
+protection	O
+and	O
+primer	O
+extension	O
+assays	O
+confirmed	O
+that	O
+the	O
+5	O
+'	O
+non	O
+-	O
+coding	O
+exon	O
+is	O
+included	O
+in	O
+the	O
+DDT1	O
+aFGF	B-GENE
+mRNA	I-GENE
+and	O
+that	O
+a	O
+major	O
+transcription	O
+start	O
+site	O
+is	O
+approximately	O
+136	O
+bp	O
+upstream	O
+of	O
+the	O
+5	O
+'	O
+non	O
+-	O
+coding	O
+splice	O
+junction	O
+of	O
+this	O
+exon	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+FK	O
+506	O
+is	O
+a	O
+useful	O
+immunosuppressive	O
+agent	O
+in	O
+kidney	O
+transplantation	O
+.	O
+
+The	O
+roles	O
+of	O
+phorbol	O
+esters	O
+and	O
+cyclic	O
+AMP	O
+in	O
+mediating	O
+the	O
+GnRH	B-GENE
+response	O
+were	O
+also	O
+investigated	O
+.	O
+
+RT	O
+-	O
+PCR	O
+using	O
+1	O
+.	O
+D	O
+-	O
+specific	O
+primers	O
+showed	O
+that	O
+kidney	O
+,	O
+brain	O
+and	O
+prostate	O
+do	O
+not	O
+express	O
+1	O
+.	O
+D	O
+mRNA	O
+even	O
+though	O
+kidney	O
+and	O
+brain	O
+are	O
+the	O
+most	O
+abundant	O
+source	O
+for	O
+aFGF	B-GENE
+protein	I-GENE
+.	O
+
+Molecular	O
+cloning	O
+and	O
+characterization	O
+of	O
+two	O
+genes	B-GENE
+encoding	I-GENE
+gp138	I-GENE
+,	O
+a	O
+cell	O
+surface	O
+glycoprotein	O
+involved	O
+in	O
+the	O
+sexual	O
+cell	O
+fusion	O
+of	O
+Dictyostelium	O
+discoideum	O
+.	O
+
+Two	O
+-	O
+dimensional	O
+phosphotryptic	O
+analyses	O
+indicate	O
+that	O
+phosphorylation	O
+on	O
+Ser	O
+-	O
+12	O
+and	O
+Ser	O
+-	O
+48	O
+in	O
+unstimulated	O
+cells	O
+is	O
+associated	O
+with	O
+the	O
+ability	O
+of	O
+overexpressed	O
+pp60c	B-GENE
+-	I-GENE
+src	I-GENE
+to	O
+potentiate	O
+beta	O
+-	O
+adrenergic	O
+signalling	O
+.	O
+
+Piroximone	O
+is	O
+a	O
+new	O
+phosphodiesterase	B-GENE
+III	I-GENE
+inhibitor	O
+that	O
+combines	O
+inotropic	O
+and	O
+vasodilator	O
+properties	O
+.	O
+
+Cytogenetic	O
+studies	O
+were	O
+performed	O
+in	O
+lymphocytes	O
+from	O
+hospital	O
+workers	O
+exposed	O
+to	O
+low	O
+doses	O
+of	O
+radiation	O
+(	O
+1	O
+.	O
+6	O
+-	O
+42	O
+.	O
+71	O
+mSv	O
+)	O
+.	O
+
+To	O
+study	O
+the	O
+origin	O
+of	O
+different	O
+fMLF	B-GENE
+-	I-GENE
+R	I-GENE
+transcripts	I-GENE
+,	O
+the	O
+genetic	O
+linkage	O
+of	O
+chemotactic	O
+receptor	O
+genes	O
+,	O
+and	O
+the	O
+regulation	O
+of	O
+fMLF	B-GENE
+-	I-GENE
+R	I-GENE
+gene	I-GENE
+expression	O
+,	O
+we	O
+determined	O
+the	O
+copy	O
+number	O
+,	O
+chromosomal	O
+location	O
+,	O
+structural	O
+organization	O
+,	O
+and	O
+5	O
+'	O
+-	O
+flanking	O
+sequence	O
+of	O
+the	O
+human	B-GENE
+fMLF	I-GENE
+-	I-GENE
+R	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+first	O
+exon	O
+encodes	O
+66	O
+bp	O
+of	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+sequence	O
+,	O
+while	O
+exon	O
+2	O
+encodes	O
+the	O
+coding	O
+and	O
+3	O
+'	O
+-	O
+untranslated	O
+sequences	O
+.	O
+
+The	O
+genomic	O
+structure	O
+of	O
+four	O
+members	O
+of	O
+the	O
+SRC	B-GENE
+-	I-GENE
+family	I-GENE
+revealed	O
+nearly	O
+identical	O
+exon	O
+/	O
+intron	O
+boundaries	O
+within	O
+the	O
+catalytic	O
+domain	O
+of	O
+this	O
+family	O
+.	O
+
+Since	O
+we	O
+have	O
+observed	O
+effects	O
+of	O
+growth	O
+factors	O
+and	O
+cAMP	O
+as	O
+well	O
+as	O
+estradiol	O
+(	O
+E2	O
+)	O
+on	O
+regulation	O
+of	O
+expression	O
+of	O
+some	O
+genes	O
+stimulated	O
+by	O
+the	O
+estrogen	B-GENE
+receptor	I-GENE
+(	O
+ER	B-GENE
+)	O
+,	O
+we	O
+have	O
+undertaken	O
+studies	O
+to	O
+examine	O
+directly	O
+whether	O
+activators	O
+of	O
+protein	O
+kinases	O
+can	O
+modulate	O
+transcriptional	O
+activity	O
+of	O
+the	O
+ER	B-GENE
+.	O
+
+Using	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+,	O
+Whipple	O
+-	O
+specific	O
+DNA	O
+fragments	O
+of	O
+284	O
+base	O
+pairs	O
+from	O
+the	O
+genome	O
+of	O
+the	O
+Whipple	O
+bacterium	O
+(	O
+Tropheryma	O
+whippelii	O
+)	O
+were	O
+demonstrated	O
+.	O
+
+RNA	B-GENE
+polymerase	I-GENE
+bound	O
+to	O
+the	O
++	O
+10A	O
+promoter	O
+partially	O
+protects	O
+a	O
+20	O
+base	O
+-	O
+pair	O
+sequence	O
+from	O
+DNase	B-GENE
+I	I-GENE
+digestion	O
+upstream	O
+of	O
+the	O
+start	O
+site	O
+.	O
+
+Salivary	O
+sodium	O
+,	O
+calcium	O
+,	O
+and	O
+magnesium	O
+concentrations	O
+were	O
+significantly	O
+higher	O
+in	O
+the	O
+SLE	O
+patients	O
+with	O
+systemic	O
+lupus	O
+erythematosus	O
+,	O
+whereas	O
+potassium	O
+and	O
+total	O
+protein	O
+concentrations	O
+and	O
+amylase	B-GENE
+activity	O
+did	O
+not	O
+differ	O
+significantly	O
+from	O
+the	O
+controls	O
+.	O
+
+Chem	O
+.	O
+
+Recombinant	O
+plasmid	O
+pFV100	O
+was	O
+subsequently	O
+isolated	O
+by	O
+its	O
+ability	O
+to	O
+complement	O
+B	O
+-	O
+band	O
+expression	O
+in	O
+ge6	B-GENE
+.	O
+
+The	O
+immunosuppressant	O
+FK506	O
+inhibits	O
+amino	O
+acid	O
+import	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Protein	O
+phosphorylation	O
+appears	O
+to	O
+play	O
+a	O
+critical	O
+role	O
+in	O
+uPA	B-GENE
+gene	I-GENE
+expression	O
+in	O
+these	O
+cells	O
+;	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+-	O
+activating	O
+phorbol	O
+esters	O
+cooperate	O
+with	O
+pp60v	B-GENE
+-	I-GENE
+src	I-GENE
+to	O
+synergistically	O
+increase	O
+uPA	B-GENE
+mRNA	I-GENE
+,	O
+whereas	O
+cyclic	B-GENE
+AMP	I-GENE
+(	I-GENE
+cAMP	I-GENE
+)	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+-	O
+activating	O
+agents	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+8	O
+-	O
+bromo	O
+cAMP	O
+)	O
+repress	O
+uPA	B-GENE
+mRNA	I-GENE
+levels	O
+.	O
+
+This	O
+300	O
+bp	O
+5	O
+'	O
+-	O
+upstream	O
+sequence	O
+of	O
+K3	B-GENE
+keratin	I-GENE
+gene	I-GENE
+,	O
+which	O
+can	O
+function	O
+in	O
+vitro	O
+as	O
+a	O
+keratinocyte	O
+-	O
+specific	O
+promoter	O
+,	O
+contains	O
+two	O
+clusters	O
+of	O
+partially	O
+overlapping	O
+motifs	O
+,	O
+one	O
+with	O
+an	O
+NFkB	B-GENE
+consensus	O
+sequence	O
+and	O
+another	O
+with	O
+a	O
+GC	O
+box	O
+.	O
+
+BACKGROUND	O
+:	O
+Delineation	O
+of	O
+the	O
+morphologic	O
+aspects	O
+of	O
+age	O
+-	O
+related	O
+macular	O
+degeneration	O
+(	O
+ARMD	O
+)	O
+is	O
+helpful	O
+in	O
+correlation	O
+with	O
+the	O
+clinical	O
+features	O
+and	O
+may	O
+contribute	O
+to	O
+understanding	O
+the	O
+pathogenesis	O
+.	O
+
+An	O
+abundant	O
+1	O
+.	O
+1	O
+-	O
+kb	O
+virion	O
+-	O
+sense	O
+polyadenylated	O
+RNA	O
+and	O
+four	O
+complementary	O
+-	O
+sense	O
+polyadenylated	O
+RNAs	O
+of	O
+1	O
+.	O
+7	O
+,	O
+1	O
+.	O
+5	O
+,	O
+1	O
+.	O
+3	O
+,	O
+and	O
+0	O
+.	O
+7	O
+kb	O
+have	O
+been	O
+identified	O
+by	O
+northern	O
+blot	O
+hybridization	O
+,	O
+confirming	O
+the	O
+bidirectional	O
+transcription	O
+strategy	O
+implied	O
+by	O
+the	O
+arrangement	O
+of	O
+ORFs	O
+.	O
+
+Risk	O
+factors	O
+associated	O
+with	O
+a	O
+high	O
+seroprevalence	O
+of	O
+hepatitis	O
+C	O
+virus	O
+infection	O
+in	O
+Egyptian	O
+blood	O
+donors	O
+.	O
+
+Here	O
+the	O
+cloning	O
+and	O
+molecular	O
+analysis	O
+of	O
+the	O
+Zm	B-GENE
+-	I-GENE
+ERabp1	I-GENE
+,	O
+Zm	B-GENE
+-	I-GENE
+ERabp4	I-GENE
+,	O
+and	O
+Zm	B-GENE
+-	I-GENE
+ERabp5	I-GENE
+genes	I-GENE
+is	O
+presented	O
+.	O
+
+This	O
+agent	O
+,	O
+isolated	O
+from	O
+the	O
+fungus	O
+Streptomyces	O
+tsukubaensis	O
+,	O
+has	O
+a	O
+mechanism	O
+of	O
+action	O
+similar	O
+to	O
+that	O
+of	O
+cyclosporine	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+of	O
+the	O
+proximal	O
+promoter	O
+revealed	O
+four	O
+regions	O
+of	O
+protection	O
+.	O
+
+Finally	O
+,	O
+the	O
+stability	O
+of	O
+the	O
+nucleotide	O
+binding	O
+function	O
+of	O
+the	O
+two	O
+proteins	O
+is	O
+similar	O
+as	O
+assessed	O
+by	O
+sensitivity	O
+to	O
+urea	O
+.	O
+
+In	O
+addition	O
+,	O
+an	O
+mck1	B-GENE
+mds1	B-GENE
+mrk1	B-GENE
+triple	O
+disruptant	O
+was	O
+viable	O
+.	O
+
+However	O
+,	O
+there	O
+were	O
+some	O
+properties	O
+of	O
+Rak	B-GENE
+that	O
+are	O
+distinct	O
+from	O
+Src	B-GENE
+-	I-GENE
+like	I-GENE
+kinases	I-GENE
+:	O
+(	O
+a	O
+)	O
+expression	O
+of	O
+Rak	B-GENE
+was	O
+predominantly	O
+in	O
+epithelial	O
+-	O
+derived	O
+cell	O
+lines	O
+and	O
+tissues	O
+,	O
+especially	O
+normal	O
+liver	O
+and	O
+kidney	O
+,	O
+and	O
+cell	O
+lines	O
+of	O
+breast	O
+and	O
+colon	O
+origin	O
+;	O
+(	O
+b	O
+)	O
+Rak	B-GENE
+does	O
+not	O
+harbor	O
+the	O
+NH2	O
+-	O
+terminal	O
+glycine	O
+essential	O
+for	O
+myristylation	O
+and	O
+membrane	O
+localization	O
+;	O
+and	O
+(	O
+c	O
+)	O
+Rak	B-GENE
+possesses	O
+a	O
+putative	O
+bipartite	O
+nuclear	O
+localization	O
+signal	O
+in	O
+the	O
+SH2	B-GENE
+domain	I-GENE
+,	O
+and	O
+subcellular	O
+fractionation	O
+studies	O
+revealed	O
+that	O
+p54rak	B-GENE
+resides	O
+predominantly	O
+in	O
+the	O
+nucleus	O
+.	O
+
+A	O
+small	O
+amount	O
+of	O
+HSP81	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+was	O
+detected	O
+only	O
+in	O
+roots	O
+.	O
+
+Cell	O
+adhesion	O
+and	O
+migration	O
+assays	O
+demonstrate	O
+that	O
+alpha	B-GENE
+6	I-GENE
+beta	I-GENE
+1	I-GENE
+is	O
+the	O
+major	O
+laminin	B-GENE
+receptor	I-GENE
+in	O
+undifferentiated	O
+F9	O
+cells	O
+as	O
+well	O
+as	O
+F9	O
+-	O
+derived	O
+PE	O
+cells	O
+.	O
+
+No	O
+local	O
+destruction	O
+by	O
+tumor	O
+or	O
+infection	O
+could	O
+be	O
+demonstrated	O
+apart	O
+from	O
+HIV	O
+infection	O
+.	O
+
+Among	O
+the	O
+mixed	O
+race	O
+persons	O
+one	O
+Chukcha	O
+-	O
+Eskimo	O
+had	O
+AS	O
+,	O
+one	O
+Eskimo	O
+-	O
+Russian	O
+had	O
+psoriatic	O
+arthritis	O
+(	O
+PsA	O
+)	O
+.	O
+
+Our	O
+data	O
+complement	O
+other	O
+studies	O
+of	O
+circumpolar	O
+populations	O
+and	O
+reinforce	O
+the	O
+reported	O
+high	O
+prevalences	O
+of	O
+SPA	O
+and	O
+HLA	B-GENE
+-	I-GENE
+B27	I-GENE
+among	O
+those	O
+populations	O
+.	O
+
+Clinical	O
+studies	O
+SY5555	O
+was	O
+administered	O
+to	O
+45	O
+patients	O
+with	O
+various	O
+infectious	O
+diseases	O
+(	O
+2	O
+with	O
+acute	O
+pharyngitis	O
+,	O
+8	O
+with	O
+acute	O
+tonsillitis	O
+,	O
+4	O
+with	O
+lacunar	O
+tonsillitis	O
+,	O
+3	O
+each	O
+with	O
+acute	O
+bronchitis	O
+,	O
+pneumonia	O
+and	O
+pertussis	O
+,	O
+7	O
+with	O
+scarlet	O
+fever	O
+,	O
+3	O
+with	O
+impetigo	O
+contagiosa	O
+,	O
+6	O
+with	O
+acute	O
+urinary	O
+tract	O
+infections	O
+,	O
+2	O
+with	O
+balanoposthitis	O
+and	O
+1	O
+each	O
+with	O
+cervical	O
+lymphadenitis	O
+,	O
+S	O
+.	O
+S	O
+.	O
+S	O
+.	O
+S	O
+.	O
+,	O
+vulvitis	O
+and	O
+acute	O
+colitis	O
+)	O
+at	O
+daily	O
+doses	O
+between	O
+3	O
+.	O
+4	O
+-	O
+10	O
+mg	O
+/	O
+kg	O
+,	O
+t	O
+.	O
+i	O
+.	O
+d	O
+.	O
+,	O
+for	O
+3	O
+-	O
+14	O
+days	O
+.	O
+
+Although	O
+most	O
+SH2	B-GENE
+-	O
+pTyr	B-GENE
+interactions	O
+occur	O
+between	O
+two	O
+different	O
+types	O
+of	O
+molecules	O
+,	O
+some	O
+appear	O
+to	O
+involve	O
+only	O
+a	O
+single	O
+molecular	O
+type	O
+.	O
+
+RESULTS	O
+:	O
+Closure	O
+time	O
+of	O
+fistulas	O
+in	O
+patients	O
+receiving	O
+TPN	O
++	O
+somatostatin	B-GENE
+was	O
+significantly	O
+shorter	O
+(	O
+13	O
+.	O
+86	O
++	O
+/	O
+-	O
+1	O
+.	O
+84	O
+versus	O
+20	O
+.	O
+4	O
++	O
+/	O
+-	O
+2	O
+.	O
+89	O
+days	O
+)	O
+than	O
+in	O
+those	O
+receiving	O
+TPN	O
+alone	O
+.	O
+
+Scratching	O
+during	O
+sleep	O
+in	O
+children	O
+with	O
+atopic	O
+dermatitis	O
+is	O
+associated	O
+with	O
+increased	O
+VO2	O
+.	O
+
+Within	O
+-	O
+subject	O
+BP	O
+differences	O
+between	O
+fish	O
+oil	O
+and	O
+corn	O
+oil	O
+treatment	O
+were	O
+similar	O
+for	O
+Dinamap	O
+(	O
+3	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+8	O
+/	O
+2	O
+.	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+mm	O
+Hg	O
+)	O
+and	O
+for	O
+24	O
+-	O
+h	O
+ABP	O
+(	O
+2	O
+.	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+/	O
+2	O
+.	O
+3	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+mm	O
+Hg	O
+)	O
+,	O
+but	O
+were	O
+more	O
+significant	O
+with	O
+the	O
+latter	O
+.	O
+
+Escherichia	O
+coli	O
+JRG582	O
+is	O
+an	O
+ampD	B-GENE
+ampE	B-GENE
+deletion	O
+derivative	O
+of	O
+strain	O
+HfrH	O
+and	O
+accordingly	O
+it	O
+is	O
+derepressed	O
+for	O
+expression	O
+of	O
+the	O
+cloned	O
+inducible	O
+beta	B-GENE
+-	I-GENE
+lactamase	I-GENE
+gene	I-GENE
+of	O
+Citrobacter	O
+freundii	O
+,	O
+carried	O
+on	O
+plasmid	O
+pNU305	O
+.	O
+
+Such	O
+a	O
+mechanism	O
+may	O
+allow	O
+acceleration	O
+of	O
+degenerative	O
+joint	O
+conditions	O
+,	O
+and	O
+may	O
+account	O
+for	O
+the	O
+increased	O
+prevalence	O
+of	O
+such	O
+conditions	O
+seen	O
+with	O
+HMS	O
+subjects	O
+.	O
+
+Solitary	O
+thyroid	O
+nodule	O
+.	O
+
+Male	O
+contraception	O
+:	O
+ideas	O
+for	O
+the	O
+future	O
+.	O
+
+While	O
+daily	O
+food	O
+intake	O
+was	O
+almost	O
+constant	O
+regardless	O
+of	O
+the	O
+dietary	O
+protein	O
+level	O
+,	O
+water	O
+intake	O
+and	O
+urine	O
+volume	O
+increased	O
+with	O
+increasing	O
+the	O
+dietary	O
+protein	O
+.	O
+
+We	O
+propose	O
+that	O
+Mad	B-GENE
+and	O
+Medea	B-GENE
+encode	O
+rate	O
+-	O
+limiting	O
+components	O
+integral	O
+to	O
+dpp	B-GENE
+pathways	O
+throughout	O
+development	O
+.	O
+
+Transcriptional	O
+regulation	O
+of	O
+the	O
+vacuolar	B-GENE
+H	I-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+ATPase	I-GENE
+B2	I-GENE
+subunit	I-GENE
+gene	I-GENE
+in	O
+differentiating	O
+THP	O
+-	O
+1	O
+cells	O
+.	O
+
+However	O
+,	O
+the	O
+inability	O
+to	O
+export	O
+RNA	O
+from	O
+the	O
+nucleus	O
+to	O
+the	O
+cytoplasm	O
+was	O
+not	O
+limited	O
+to	O
+a	O
+particular	O
+phase	O
+of	O
+the	O
+cell	O
+division	O
+cycle	O
+.	O
+
+An	O
+E	O
+box	O
+element	O
+is	O
+required	O
+for	O
+the	O
+expression	O
+of	O
+the	O
+ad4bp	B-GENE
+gene	I-GENE
+,	O
+a	O
+mammalian	B-GENE
+homologue	I-GENE
+of	I-GENE
+ftz	I-GENE
+-	I-GENE
+f1	I-GENE
+gene	I-GENE
+,	O
+which	O
+is	O
+essential	O
+for	O
+adrenal	O
+and	O
+gonadal	O
+development	O
+.	O
+
+Inhibition	O
+assays	O
+performed	O
+with	O
+over	O
+30	O
+different	O
+natural	O
+and	O
+synthetic	O
+sialylated	O
+and	O
+/	O
+or	O
+sulfated	O
+compounds	O
+are	O
+utilized	O
+to	O
+define	O
+in	O
+greater	O
+detail	O
+specific	O
+structural	O
+features	O
+involved	O
+in	O
+oligosaccharide	O
+-	O
+protein	O
+binding	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+protein	O
+in	O
+the	O
+region	O
+of	O
+the	O
+specificity	O
+pocket	O
+is	O
+similar	O
+to	O
+that	O
+of	O
+S	B-GENE
+.	I-GENE
+griseus	I-GENE
+proteases	I-GENE
+A	I-GENE
+,	I-GENE
+B	I-GENE
+,	I-GENE
+and	I-GENE
+C	I-GENE
+.	O
+
+This	O
+experimental	O
+design	O
+was	O
+used	O
+to	O
+determine	O
+the	O
+effect	O
+of	O
+displacement	O
+of	O
+the	O
+alpha	B-GENE
+4	I-GENE
+-	I-GENE
+2	I-GENE
+binding	I-GENE
+site	I-GENE
+on	O
+the	O
+repression	O
+of	O
+alpha	B-GENE
+4	I-GENE
+gene	I-GENE
+transcription	O
+by	O
+ICP4	B-GENE
+.	O
+
+Immediate	O
+-	O
+early	O
+transcription	O
+from	O
+the	O
+channel	O
+catfish	O
+virus	O
+genome	O
+:	O
+characterization	O
+of	O
+two	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+transcripts	I-GENE
+.	O
+
+The	O
+GRE	O
+at	O
+nucleotide	O
+7640	O
+is	O
+a	O
+composite	O
+GRE	O
+(	O
+cGRE	O
+)	O
+containing	O
+an	O
+overlapping	O
+activator	B-GENE
+protein	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+motif	O
+for	O
+the	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+homodimer	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+/	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+heterodimer	O
+.	O
+
+In	O
+contrast	O
+to	O
+some	O
+results	O
+previously	O
+published	O
+for	O
+a	O
+very	O
+close	O
+sequence	O
+variant	O
+(	O
+see	O
+ref	O
+.	O
+
+Transcriptional	O
+activation	O
+by	O
+thyroid	O
+hormone	O
+(	O
+T3	O
+)	O
+requires	O
+interactions	O
+between	O
+the	O
+T3	B-GENE
+receptor	I-GENE
+(	O
+TR	B-GENE
+)	O
+and	O
+T3	O
+response	O
+elements	O
+(	O
+TREs	O
+)	O
+composed	O
+of	O
+two	O
+copies	O
+of	O
+sequences	O
+related	O
+to	O
+AGGTCA	O
+.	O
+
+A	O
+multivariate	O
+analysis	O
+of	O
+risk	O
+factors	O
+for	O
+relapse	O
+examined	O
+age	O
+,	O
+WBC	O
+at	O
+diagnosis	O
+,	O
+blast	O
+count	O
+at	O
+diagnosis	O
+,	O
+percentage	O
+of	O
+marrow	O
+blasts	O
+,	O
+FAB	B-GENE
+subtype	O
+,	O
+the	O
+number	O
+of	O
+remission	O
+induction	O
+courses	O
+to	O
+achieve	O
+a	O
+remission	O
+,	O
+maintenance	O
+therapy	O
+,	O
+consolidation	O
+therapy	O
+,	O
+marrow	O
+cell	O
+dose	O
+,	O
+donor	O
+-	O
+recipient	O
+sex	O
+,	O
+GVHD	O
+prophylaxis	O
+regimen	O
+and	O
+isolation	O
+and	O
+decontamination	O
+in	O
+laminar	O
+airflow	O
+rooms	O
+.	O
+
+Carnitine	B-GENE
+palmitoyltransferase	I-GENE
+(	I-GENE
+CPT	I-GENE
+)	I-GENE
+II	I-GENE
+deficiency	O
+is	O
+the	O
+most	O
+common	O
+inherited	O
+disorder	O
+of	O
+lipid	O
+metabolism	O
+affecting	O
+skeletal	O
+muscle	O
+.	O
+
+We	O
+show	O
+that	O
+these	O
+three	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+mutants	O
+differ	O
+considerably	O
+in	O
+their	O
+ability	O
+to	O
+bypass	O
+the	O
+sex	O
+determination	O
+signal	O
+,	O
+with	O
+SxlM4	B-GENE
+being	O
+the	O
+strongest	O
+and	O
+SxlM1	B-GENE
+the	O
+weakest	O
+.	O
+
+We	O
+show	O
+that	O
+these	O
+three	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+mutants	O
+differ	O
+considerably	O
+in	O
+their	O
+ability	O
+to	O
+bypass	O
+the	O
+sex	O
+determination	O
+signal	O
+,	O
+with	O
+SxlM4	B-GENE
+being	O
+the	O
+strongest	O
+and	O
+SxlM1	B-GENE
+the	O
+weakest	O
+.	O
+
+Blood	O
+pressure	O
+also	O
+was	O
+increased	O
+by	O
+lidocaine	O
+(	O
+6	O
+mg	O
+kg	O
+-	O
+1	O
+)	O
+.	O
+
+Anesthesiologists	O
+often	O
+use	O
+more	O
+than	O
+one	O
+drug	O
+in	O
+a	O
+patient	O
+to	O
+achieve	O
+a	O
+target	O
+response	O
+,	O
+such	O
+as	O
+a	O
+desired	O
+blood	O
+pressure	O
+.	O
+
+We	O
+suggest	O
+that	O
+this	O
+gene	O
+cluster	O
+codes	O
+for	O
+(	O
+parts	O
+of	O
+)	O
+a	O
+multisubunit	B-GENE
+cytochrome	I-GENE
+c	I-GENE
+haem	I-GENE
+lyase	I-GENE
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+a	O
+comparison	O
+between	O
+the	O
+number	O
+and	O
+shape	O
+of	O
+corneal	O
+endothelial	O
+cells	O
+has	O
+been	O
+performed	O
+in	O
+25	O
+patients	O
+before	O
+and	O
+6	O
+months	O
+after	O
+PRK	O
+.	O
+
+Standard	O
+reference	O
+sources	O
+indicate	O
+that	O
+an	O
+able	O
+-	O
+bodied	O
+11	O
+-	O
+year	O
+-	O
+old	O
+child	O
+of	O
+comparable	O
+height	O
+requires	O
+1	O
+,	O
+493	O
+kcal	O
+/	O
+d	O
+for	O
+support	O
+of	O
+basal	O
+metabolic	O
+functions	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+myoD	B-GENE
+promoter	I-GENE
+,	O
+the	O
+myoD	B-GENE
+enhancer	I-GENE
+shows	O
+striking	O
+conservation	O
+between	O
+humans	O
+and	O
+mice	O
+both	O
+in	O
+its	O
+sequence	O
+and	O
+its	O
+distal	O
+position	O
+.	O
+
+However	O
+,	O
+a	O
+clear	O
+difference	O
+exists	O
+between	O
+myoblasts	O
+and	O
+10T1	O
+/	O
+2	O
+cells	O
+(	O
+and	O
+other	O
+non	O
+-	O
+muscle	O
+cell	O
+types	O
+)	O
+in	O
+the	O
+chromatin	O
+structure	O
+of	O
+the	O
+chromosomal	O
+myoD	B-GENE
+core	I-GENE
+enhancer	I-GENE
+,	O
+suggesting	O
+that	O
+the	O
+myoD	B-GENE
+enhancer	I-GENE
+is	O
+repressed	O
+by	O
+epigenetic	O
+mechanisms	O
+in	O
+10T1	O
+/	O
+2	O
+cells	O
+.	O
+
+Using	O
+Ki	B-GENE
+-	I-GENE
+ras	I-GENE
+-	O
+transformed	O
+3T3	O
+cells	O
+as	O
+a	O
+model	O
+system	O
+,	O
+we	O
+show	O
+that	O
+both	O
+RA	O
+and	O
+the	O
+'	O
+dissociating	O
+'	O
+retinoids	O
+inhibit	O
+anchorage	O
+-	O
+independent	O
+cell	O
+proliferation	O
+,	O
+suggesting	O
+that	O
+retinoid	O
+-	O
+induced	O
+growth	O
+inhibition	O
+may	O
+be	O
+related	O
+to	O
+AP1	B-GENE
+transrepression	O
+.	O
+
+The	O
+Oct	B-GENE
+and	O
+HMG2	B-GENE
+proteins	I-GENE
+also	O
+interact	O
+in	O
+vivo	O
+.	O
+
+Atopic	O
+dermatitis	O
+is	O
+an	O
+"	O
+itch	O
+which	O
+rashes	O
+and	O
+not	O
+a	O
+rash	O
+which	O
+itches	O
+"	O
+and	O
+therefore	O
+,	O
+any	O
+patient	O
+treatment	O
+program	O
+should	O
+address	O
+the	O
+multiplicity	O
+of	O
+potential	O
+trigger	O
+factors	O
+that	O
+provoke	O
+this	O
+itching	O
+.	O
+
+Primer	O
+extension	O
+experiments	O
+showed	O
+that	O
+there	O
+are	O
+two	O
+transcription	O
+initiation	O
+sites	O
+16	O
+bp	O
+apart	O
+in	O
+the	O
+mouse	B-GENE
+type	I-GENE
+2	I-GENE
+receptor	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+beta	O
+subunit	O
+of	O
+the	O
+Fc	B-GENE
+epsilon	I-GENE
+R1	I-GENE
+is	O
+a	O
+33	O
+-	O
+kDa	O
+tyrosine	O
+phosphoprotein	O
+,	O
+but	O
+the	O
+p33	B-GENE
+Grb2	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+described	O
+in	O
+the	O
+present	O
+report	O
+is	O
+not	O
+the	O
+Fc	B-GENE
+epsilon	I-GENE
+R1	I-GENE
+beta	I-GENE
+chain	I-GENE
+and	O
+its	O
+identity	O
+is	O
+unknown	O
+.	O
+
+To	O
+study	O
+the	O
+mechanisms	O
+as	O
+well	O
+as	O
+magnitude	O
+of	O
+the	O
+transmembrane	O
+transfer	O
+of	O
+bacterial	O
+products	O
+from	O
+the	O
+dialysate	O
+,	O
+we	O
+developed	O
+a	O
+computerized	O
+in	O
+vitro	O
+dialysis	O
+model	O
+which	O
+provides	O
+continuous	O
+pressure	O
+recording	O
+from	O
+the	O
+arterial	O
+,	O
+venous	O
+,	O
+dialysate	O
+inflow	O
+and	O
+outflow	O
+ports	O
+.	O
+
+After	O
+24	O
+hour	O
+incubation	O
+,	O
+total	O
+cell	O
+-	O
+associated	O
+IL	B-GENE
+-	I-GENE
+1Ra	I-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+were	O
+measured	O
+by	O
+specific	O
+radioimmunoassay	O
+.	O
+
+1972	O
+.	O
+
+In	O
+contrast	O
+,	O
+recent	O
+evidence	O
+suggests	O
+that	O
+children	O
+with	O
+sickle	B-GENE
+-	I-GENE
+hemoglobin	I-GENE
+C	I-GENE
+disease	O
+do	O
+not	O
+develop	O
+functional	O
+asplenia	O
+before	O
+3	O
+to	O
+4	O
+years	O
+of	O
+age	O
+and	O
+thus	O
+may	O
+not	O
+benefit	O
+from	O
+penicillin	O
+prophylaxis	O
+.	O
+
+Deletion	O
+analysis	O
+indicates	O
+that	O
+TBP	B-GENE
+and	O
+hTAFII18	B-GENE
+bind	O
+to	O
+distinct	O
+domains	O
+of	O
+hTAFII28	B-GENE
+.	O
+hTAFII18	B-GENE
+also	O
+interacts	O
+with	O
+TBP	B-GENE
+,	O
+but	O
+it	O
+interacts	O
+more	O
+strongly	O
+with	O
+hTAFII28	B-GENE
+and	O
+hTAFII30	B-GENE
+.	O
+
+Vascular	O
+endothelial	O
+cells	O
+undergo	O
+profound	O
+changes	O
+upon	O
+cellular	O
+activation	O
+including	O
+expression	O
+of	O
+a	O
+spectrum	O
+of	O
+cell	O
+activation	O
+-	O
+associated	O
+genes	O
+.	O
+
+Because	O
+ATF	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+CREM	B-GENE
+are	O
+known	O
+to	O
+bind	O
+to	O
+cAMP	O
+response	O
+elements	O
+(	O
+CRE	O
+)	O
+,	O
+this	O
+functional	O
+sequence	O
+was	O
+named	O
+the	O
+kappa	B-GENE
+E3	I-GENE
+'	I-GENE
+-	O
+CRE	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+known	O
+largest	O
+subunits	O
+of	O
+DdRPs	B-GENE
+from	O
+different	O
+species	O
+contain	O
+highly	O
+conserved	O
+regions	O
+.	O
+
+The	O
+TTG	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+has	O
+been	O
+identified	O
+at	O
+the	O
+site	O
+of	O
+chromosomal	O
+translocations	O
+in	O
+acute	O
+T	O
+-	O
+cell	O
+leukemia	O
+'	O
+s	O
+(	O
+T	O
+-	O
+ALL	O
+)	O
+.	O
+
+In	O
+vitro	O
+studies	O
+with	O
+blood	O
+cells	O
+incubated	O
+with	O
+acetate	O
+or	O
+bicarbonate	O
+ions	O
+in	O
+concentrations	O
+,	O
+which	O
+are	O
+observed	O
+in	O
+vivo	O
+during	O
+hemodialysis	O
+,	O
+suggest	O
+that	O
+probably	O
+these	O
+ions	O
+do	O
+not	O
+directly	O
+affect	O
+superoxide	O
+anions	O
+generation	O
+,	O
+erythrocyte	O
+SOD	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+catalase	B-GENE
+activities	O
+and	O
+erythrocyte	O
+membrane	O
+lipid	O
+peroxidation	O
+.	O
+
+Short	O
+therapy	O
+with	O
+omeprazole	O
+20	O
+mg	O
+/	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+,	O
+clarithromycin	O
+500	O
+mg	O
+/	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+,	O
+and	O
+CBS	O
+120	O
+mg	O
+/	O
+q	O
+.	O
+i	O
+.	O
+d	O
+.	O
+is	O
+a	O
+safe	O
+,	O
+well	O
+tolerated	O
+combination	O
+that	O
+achieves	O
+a	O
+80	O
+.	O
+6	O
+%	O
+eradication	O
+rate	O
+of	O
+H	O
+.	O
+pylori	O
+and	O
+duodenal	O
+ulcer	O
+healing	O
+rates	O
+as	O
+good	O
+as	O
+those	O
+achieved	O
+by	O
+omeprazole	O
+20	O
+mg	O
+/	O
+d	O
+when	O
+given	O
+for	O
+4	O
+wk	O
+.	O
+
+The	O
+concentration	O
+of	O
+mite	O
+allergen	O
+was	O
+very	O
+low	O
+(	O
+mean	O
+0	O
+.	O
+18	O
+micrograms	O
+Der	O
+p	O
+milligrams	O
+sieved	O
+house	O
+dust	O
+)	O
+,	O
+whereas	O
+that	O
+of	O
+cat	O
+allergen	O
+was	O
+high	O
+in	O
+homes	O
+with	O
+a	O
+cat	O
+(	O
+80	O
+.	O
+8	O
+micrograms	O
+Fel	O
+d	O
+milligrams	O
+)	O
+but	O
+also	O
+in	O
+homes	O
+with	O
+no	O
+cat	O
+(	O
+3	O
+.	O
+2	O
+micrograms	O
+Fel	O
+d	O
+milligrams	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+A	O
+comparison	O
+of	O
+the	O
+LysU	B-GENE
+crystal	O
+structure	O
+with	O
+the	O
+structures	O
+of	O
+seryl	B-GENE
+-	I-GENE
+and	I-GENE
+aspartyl	I-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetases	I-GENE
+enables	O
+a	O
+conserved	O
+core	O
+to	O
+be	O
+identified	O
+.	O
+
+Whole	O
+bowel	O
+irrigation	O
+is	O
+a	O
+recently	O
+described	O
+technique	O
+to	O
+enhance	O
+the	O
+passage	O
+of	O
+drugs	O
+already	O
+beyond	O
+the	O
+pylorus	O
+.	O
+
+The	O
+MPS1	B-GENE
+open	I-GENE
+reading	I-GENE
+frame	I-GENE
+has	O
+been	O
+fused	O
+to	O
+those	O
+that	O
+encode	O
+the	O
+LexA	B-GENE
+protein	I-GENE
+or	O
+the	O
+GST	B-GENE
+protein	I-GENE
+and	O
+both	O
+of	O
+these	O
+constructs	O
+function	O
+in	O
+yeast	O
+.	O
+
+Hematopoietic	B-GENE
+growth	I-GENE
+factors	I-GENE
+have	O
+already	O
+had	O
+an	O
+enormous	O
+impact	O
+on	O
+transfusion	O
+practice	O
+by	O
+eliminating	O
+or	O
+reducing	O
+the	O
+need	O
+for	O
+red	O
+blood	O
+cell	O
+transfusions	O
+in	O
+a	O
+variety	O
+of	O
+anemic	O
+states	O
+characterized	O
+by	O
+an	O
+absolute	O
+or	O
+relative	O
+decrease	O
+in	O
+erythropoietin	B-GENE
+.	O
+
+However	O
+,	O
+the	O
+mouse	O
+has	O
+previously	O
+been	O
+shown	O
+to	O
+possess	O
+only	O
+three	O
+forms	O
+of	O
+ADH	B-GENE
+.	O
+
+During	O
+IC	O
+breaths	O
+and	O
+following	O
+EC	O
+and	O
+VC	O
+breaths	O
+at	O
+rest	O
+,	O
+end	O
+-	O
+tidal	O
+CO2	O
+pressure	O
+(	O
+PET	O
+,	O
+CO2	O
+)	O
+fell	O
+by	O
+7	O
+.	O
+5	O
+,	O
+8	O
+.	O
+5	O
+and	O
+9	O
+.	O
+5	O
+mmHg	O
+,	O
+respectively	O
+.	O
+
+Phylogenetic	O
+analyses	O
+of	O
+19	O
+amino	O
+acid	O
+sequences	O
+of	O
+6	O
+related	O
+protein	O
+types	O
+indicate	O
+that	O
+actin	B-GENE
+-	O
+associated	O
+proteins	O
+related	O
+to	O
+gelsolin	B-GENE
+are	O
+monophyletic	O
+to	O
+a	O
+common	O
+ancestor	O
+and	O
+include	O
+flightless	B-GENE
+proteins	I-GENE
+.	O
+
+No	O
+homologs	O
+of	O
+other	O
+members	O
+of	O
+the	O
+Surfeit	B-GENE
+gene	I-GENE
+cluster	I-GENE
+were	O
+detected	O
+in	O
+close	O
+proximity	O
+to	O
+the	O
+D	O
+.	O
+melanogaster	O
+Surf	B-GENE
+-	I-GENE
+3	I-GENE
+/	O
+rpL7a	B-GENE
+gene	O
+.	O
+
+Moreover	O
+,	O
+we	O
+found	O
+that	O
+cyclin	B-GENE
+E	I-GENE
+,	O
+in	O
+contrast	O
+to	O
+cyclin	B-GENE
+D1	I-GENE
+,	O
+was	O
+required	O
+for	O
+the	O
+G1	O
+/	O
+S	O
+transition	O
+even	O
+in	O
+cells	O
+lacking	O
+retinoblastoma	B-GENE
+protein	I-GENE
+function	O
+.	O
+
+The	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+SGC1	B-GENE
+gene	I-GENE
+product	I-GENE
+includes	O
+a	O
+region	O
+with	O
+substantial	O
+similarity	O
+to	O
+the	O
+basic	O
+-	O
+helix	O
+-	O
+loop	O
+-	O
+helix	O
+domain	O
+of	O
+the	O
+Myc	B-GENE
+family	I-GENE
+of	O
+DNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+By	O
+creating	O
+Pax	B-GENE
+-	I-GENE
+6	I-GENE
+-	O
+BSAP	B-GENE
+fusion	O
+proteins	O
+,	O
+we	O
+were	O
+able	O
+to	O
+identify	O
+a	O
+short	O
+amino	O
+acid	O
+stretch	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+part	O
+of	O
+the	O
+paired	B-GENE
+domain	O
+which	O
+is	O
+responsible	O
+for	O
+these	O
+differences	O
+in	O
+DNA	O
+-	O
+binding	O
+specificity	O
+.	O
+
+To	O
+establish	O
+a	O
+possible	O
+association	O
+between	O
+familial	O
+dysfibrinogenemia	O
+and	O
+thrombophilia	O
+,	O
+data	O
+on	O
+cases	O
+with	O
+both	O
+affections	O
+were	O
+collected	O
+in	O
+a	O
+study	O
+within	O
+the	O
+framework	O
+of	O
+the	O
+SSC	O
+Subcommittee	O
+on	O
+Fibrinogen	B-GENE
+of	O
+the	O
+International	O
+Society	O
+on	O
+Thrombosis	O
+and	O
+Haemostasis	O
+.	O
+
+Conjugated	O
+estrogens	O
+shorten	O
+bleeding	O
+time	O
+in	O
+uraemia	O
+:	O
+a	O
+possible	O
+role	O
+of	O
+serotonin	O
+?	O
+
+These	O
+six	O
+districts	O
+have	O
+an	O
+area	O
+of	O
+34	O
+,	O
+000	O
+km2	O
+and	O
+hold	O
+a	O
+population	O
+of	O
+30	O
+million	O
+.	O
+
+According	O
+to	O
+symptoms	O
+,	O
+signs	O
+,	O
+imaging	O
+features	O
+,	O
+operation	O
+findings	O
+,	O
+the	O
+original	O
+places	O
+and	O
+the	O
+expansive	O
+directions	O
+of	O
+the	O
+tumor	O
+,	O
+they	O
+were	O
+divided	O
+into	O
+four	O
+clinical	O
+types	O
+:	O
+sellar	O
+,	O
+clival	O
+,	O
+occipito	O
+-	O
+temporal	O
+and	O
+extent	O
+.	O
+
+The	O
+cases	O
+included	O
+35	O
+de	O
+novo	O
+diffuse	O
+aggressive	O
+lymphomas	O
+(	O
+DAL	O
+;	O
+19	O
+large	O
+-	O
+cell	O
+,	O
+4	O
+mixed	O
+-	O
+cell	O
+,	O
+and	O
+12	O
+large	O
+-	O
+cell	O
+immunoblastic	O
+)	O
+,	O
+52	O
+transformed	O
+aggressive	O
+lymphomas	O
+derived	O
+from	O
+follicular	O
+lymphomas	O
+(	O
+TFL	O
+)	O
+,	O
+42	O
+indolent	O
+follicular	O
+lymphomas	O
+(	O
+FL	O
+)	O
+,	O
+14	O
+mantle	O
+cell	O
+lymphomas	O
+(	O
+MCL	O
+)	O
+,	O
+and	O
+27	O
+small	O
+noncleaved	O
+cell	O
+lymphomas	O
+(	O
+SNCL	O
+)	O
+.	O
+
+Icterus	O
+and	O
+beta	O
+-	O
+thalassemia	O
+in	O
+Congolese	O
+children	O
+in	O
+Brazzaville	O
+
+Female	O
+patients	O
+with	O
+breast	O
+cancer	O
+diagnosed	O
+between	O
+1982	O
+and	O
+1991	O
+at	O
+Roswell	O
+Park	O
+Cancer	O
+Institute	O
+(	O
+RPCI	O
+)	O
+in	O
+Buffalo	O
+,	O
+New	O
+York	O
+,	O
+who	O
+provided	O
+information	O
+on	O
+their	O
+cigarette	O
+smoking	O
+history	O
+at	O
+the	O
+time	O
+of	O
+their	O
+diagnosis	O
+were	O
+included	O
+.	O
+
+Upon	O
+analysis	O
+of	O
+the	O
+tissue	O
+distribution	O
+of	O
+AAMP	B-GENE
+,	O
+it	O
+was	O
+found	O
+to	O
+be	O
+expressed	O
+strongly	O
+in	O
+endothelial	O
+cells	O
+,	O
+cytotrophoblasts	O
+,	O
+and	O
+poorly	O
+differentiated	O
+colon	O
+adenocarcinoma	O
+cells	O
+found	O
+in	O
+lymphatics	O
+.	O
+
+Data	O
+from	O
+the	O
+V	O
+-	O
+HeFT	O
+II	O
+show	O
+that	O
+at	O
+2	O
+-	O
+year	O
+follow	O
+-	O
+up	O
+,	O
+a	O
+progressive	O
+rise	O
+of	O
+plasma	O
+norepinephrine	O
+was	O
+observed	O
+in	O
+both	O
+treatment	O
+arms	O
+,	O
+suggesting	O
+that	O
+disease	O
+progresses	O
+despite	O
+treatment	O
+with	O
+either	O
+an	O
+angiotensin	B-GENE
+-	I-GENE
+converting	I-GENE
+enzyme	I-GENE
+inhibitor	O
+,	O
+enalapril	O
+,	O
+or	O
+vasodilator	O
+therapy	O
+with	O
+hydralazine	O
+/	O
+isosorbide	O
+dinitrate	O
+.	O
+
+Analysis	O
+of	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+/	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+homodimerization	O
+using	O
+both	O
+in	O
+vitro	O
+binding	O
+assays	O
+as	O
+well	O
+as	O
+a	O
+yeast	O
+two	O
+-	O
+hybrid	O
+method	O
+provided	O
+evidence	O
+in	O
+support	O
+of	O
+a	O
+head	O
+-	O
+to	O
+-	O
+tail	O
+model	O
+for	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+/	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+homodimerization	O
+and	O
+revealed	O
+that	O
+sequences	O
+within	O
+the	O
+NH2	O
+-	O
+terminal	O
+A	O
+domain	O
+interact	O
+with	O
+a	O
+structure	O
+that	O
+requires	O
+the	O
+presence	O
+of	O
+both	O
+the	O
+carboxyl	O
+B	O
+and	O
+C	O
+domains	O
+in	O
+combination	O
+.	O
+
+The	O
+protein	O
+is	O
+composed	O
+of	O
+a	O
+central	O
+alpha	O
+-	O
+helical	O
+portion	O
+with	O
+globular	O
+domains	O
+at	O
+both	O
+NH2	O
+and	O
+COOH	O
+termini	O
+,	O
+and	O
+the	O
+epitope	O
+to	O
+the	O
+monoclonal	O
+antibody	O
+resides	O
+in	O
+the	O
+central	O
+alpha	O
+-	O
+helical	O
+stalk	O
+.	O
+
+Radioligand	O
+binding	O
+was	O
+indistinguishable	O
+for	O
+both	O
+transiently	O
+expressed	O
+constructs	O
+.	O
+
+Diagnosis	O
+of	O
+FHCS	O
+has	O
+been	O
+weighed	O
+upon	O
+laparoscopic	O
+findings	O
+.	O
+
+Human	B-GENE
+papillomavirus	I-GENE
+type	I-GENE
+31b	I-GENE
+late	I-GENE
+gene	I-GENE
+expression	O
+is	O
+regulated	O
+through	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+-	O
+mediated	O
+changes	O
+in	O
+RNA	O
+processing	O
+.	O
+
+Interestingly	O
+,	O
+virions	O
+also	O
+contained	O
+smaller	O
+proteins	O
+that	O
+reacted	O
+with	O
+antibodies	O
+specific	O
+for	O
+the	O
+accessory	O
+proteins	O
+as	O
+well	O
+as	O
+SN	B-GENE
+and	O
+CAT	B-GENE
+fusion	I-GENE
+partners	O
+.	O
+
+Studies	O
+using	O
+an	O
+inhibitor	O
+or	O
+a	O
+mutant	B-GENE
+Lb	I-GENE
+proteinase	I-GENE
+indicated	O
+that	O
+stimulation	O
+of	O
+IRES	O
+-	O
+driven	O
+translation	O
+is	O
+mediated	O
+via	O
+proteolysis	O
+of	O
+some	O
+cellular	O
+component	O
+(	O
+s	O
+)	O
+.	O
+
+Restriction	O
+mapping	O
+analysis	O
+localized	O
+this	O
+cDNA	O
+to	O
+the	O
+HHV	B-GENE
+-	I-GENE
+6A	I-GENE
+(	I-GENE
+U1102	I-GENE
+)	I-GENE
+genomic	I-GENE
+BamHI	I-GENE
+G	I-GENE
+fragment	I-GENE
+,	O
+at	O
+the	O
+right	O
+end	O
+of	O
+the	O
+unique	O
+long	O
+segment	O
+of	O
+the	O
+genome	O
+and	O
+to	O
+the	O
+SalI	B-GENE
+L	I-GENE
+and	O
+SalI	B-GENE
+O	I-GENE
+fragments	I-GENE
+within	O
+the	O
+left	O
+and	O
+right	O
+terminal	O
+direct	O
+repeat	O
+regions	O
+,	O
+respectively	O
+.	O
+
+For	O
+replication	O
+reporter	O
+constructs	O
+where	O
+E1	B-GENE
+and	O
+E2	B-GENE
+are	O
+supplied	O
+in	O
+trans	O
+by	O
+the	O
+respective	O
+expression	O
+vectors	O
+,	O
+distance	O
+between	O
+the	O
+half	O
+sites	O
+seems	O
+to	O
+play	O
+a	O
+major	O
+role	O
+,	O
+yet	O
+the	O
+phasing	O
+relationships	O
+are	O
+measurable	O
+.	O
+
+As	O
+it	O
+had	O
+been	O
+previously	O
+reported	O
+that	O
+the	O
+18	O
+-	O
+bp	O
+palindrome	O
+contains	O
+sufficient	O
+nucleotide	O
+sequence	O
+information	O
+for	O
+E1	B-GENE
+binding	O
+,	O
+we	O
+speculate	O
+that	O
+a	O
+minimal	O
+E1	B-GENE
+recognition	O
+motif	O
+is	O
+presented	O
+in	O
+each	O
+half	O
+site	O
+.	O
+
+METHODS	O
+:	O
+Out	O
+of	O
+171	O
+patients	O
+receiving	O
+anticoagulation	O
+between	O
+July	O
+1992	O
+and	O
+December	O
+1993	O
+,	O
+83	O
+patients	O
+with	O
+hemispheric	O
+embolisms	O
+received	O
+heparin	O
+within	O
+72	O
+hours	O
+from	O
+onset	O
+(	O
+activated	O
+partial	O
+thromboplastin	B-GENE
+time	O
+[	O
+aPTT	O
+]	O
+1	O
+.	O
+5	O
+times	O
+control	O
+value	O
+)	O
+.	O
+
+In	O
+the	O
+commercially	O
+available	O
+intravenous	O
+formulation	O
+of	O
+Cyclosporin	O
+A	O
+(	O
+Sandimmun	O
+)	O
+,	O
+polyoxyethylated	O
+castor	O
+oil	O
+(	O
+Cremophor	O
+EL	O
+)	O
+is	O
+used	O
+as	O
+a	O
+solubilizing	O
+agent	O
+.	O
+
+Sequence	O
+comparisons	O
+of	O
+prokaryotic	B-GENE
+RCR	I-GENE
+initiators	I-GENE
+has	O
+revealed	O
+a	O
+set	O
+of	O
+three	O
+common	O
+motifs	O
+,	O
+two	O
+of	O
+which	O
+,	O
+a	O
+putative	O
+metal	O
+coordination	O
+site	O
+and	O
+a	O
+downstream	O
+active	O
+-	O
+site	O
+tyrosine	O
+motif	O
+,	O
+could	O
+be	O
+tentatively	O
+identified	O
+in	O
+parvoviral	B-GENE
+replicator	I-GENE
+proteins	I-GENE
+.	O
+
+The	O
+mean	O
+marginal	O
+discrepancy	O
+of	O
+provisional	O
+restorations	O
+was	O
+compared	O
+for	O
+restorations	O
+fabricated	O
+from	O
+stone	O
+,	O
+low	O
+-	O
+viscosity	O
+poly	O
+(	O
+vinyl	O
+siloxane	O
+)	O
+,	O
+and	O
+medium	O
+-	O
+viscosity	O
+poly	O
+(	O
+vinyl	O
+siloxane	O
+)	O
+.	O
+
+The	O
+characterized	O
+Aplysia	B-GENE
+Afurin2	I-GENE
+is	O
+a	O
+candidate	O
+PC	B-GENE
+that	O
+may	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+processing	O
+of	O
+egg	B-GENE
+-	I-GENE
+laying	I-GENE
+hormone	I-GENE
+(	O
+ELH	B-GENE
+)	O
+-	O
+related	O
+precursors	O
+in	O
+the	O
+secretory	O
+cells	O
+of	O
+the	O
+atrial	O
+gland	O
+.	O
+
+Rats	O
+treated	O
+with	O
+8	O
+-	O
+OH	O
+-	O
+DPAT	O
+were	O
+not	O
+impaired	O
+in	O
+their	O
+ability	O
+to	O
+learn	O
+a	O
+visual	O
+discrimination	O
+in	O
+a	O
+water	O
+maze	O
+.	O
+
+The	O
+term	O
+endovascular	O
+papillary	O
+haemangioma	O
+is	O
+suggested	O
+.	O
+
+In	O
+addition	O
+,	O
+two	O
+internal	O
+promoters	O
+,	O
+PmiaA	B-GENE
+and	O
+P1hfq	B-GENE
+were	O
+identified	O
+and	O
+mapped	O
+to	O
+201	O
+and	O
+837	O
+nucleotides	O
+upstream	O
+from	O
+the	O
+respective	O
+translation	O
+start	O
+sites	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+mutL	B-GENE
+,	O
+miaA	B-GENE
+,	O
+and	O
+hfq	B-GENE
+expression	O
+could	O
+be	O
+regulated	O
+by	O
+multiple	O
+mechanisms	O
+,	O
+including	O
+degree	O
+of	O
+cotranscription	O
+from	O
+upstream	O
+genes	O
+,	O
+modulation	O
+of	O
+internal	O
+promoter	O
+strength	O
+,	O
+and	O
+by	O
+RNase	B-GENE
+E	I-GENE
+activity	O
+.	O
+
+Coronary	O
+T1	O
+and	O
+T2	O
+weighted	O
+images	O
+were	O
+obtained	O
+.	O
+
+The	O
+2	O
+kb	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+and	O
+the	O
+1	O
+.	O
+1	O
+kb	O
+of	O
+the	O
+entire	O
+sGTH	B-GENE
+alpha	I-GENE
+subunit	I-GENE
+coding	O
+region	O
+were	O
+sequenced	O
+from	O
+the	O
+genomic	O
+clone	O
+,	O
+sGTH	B-GENE
+alpha	I-GENE
+-	I-GENE
+G1	I-GENE
+.	O
+
+Functional	O
+analysis	O
+of	O
+the	O
+sGTH	B-GENE
+alpha	I-GENE
+subunit	I-GENE
+promoter	I-GENE
+by	O
+the	O
+transient	O
+transfection	O
+of	O
+several	O
+sGTH	B-GENE
+alpha	I-GENE
+/	O
+CAT	B-GENE
+chimeric	O
+plasmids	O
+into	O
+rainbow	O
+trout	O
+pituitary	O
+cells	O
+suggests	O
+that	O
+its	O
+pituitary	O
+-	O
+specific	O
+expression	O
+is	O
+GSE	B-GENE
+-	O
+dependent	O
+.	O
+
+Indium	O
+-	O
+111	O
+OncoScint	O
+CR	O
+/	O
+OV	O
+and	O
+F	O
+-	O
+18	O
+FDG	O
+in	O
+colorectal	O
+and	O
+ovarian	O
+carcinoma	O
+recurrences	O
+.	O
+
+His	O
+carnitine	B-GENE
+palmitoyltransferase	I-GENE
+(	I-GENE
+CPT	I-GENE
+)	I-GENE
+I	I-GENE
+and	I-GENE
+II	I-GENE
+activities	O
+were	O
+0	O
+.	O
+06	O
+and	O
+0	O
+.	O
+12	O
+nmol	O
+/	O
+min	O
+/	O
+mg	O
+protein	O
+,	O
+as	O
+compared	O
+with	O
+a	O
+mean	O
+value	O
+of	O
+0	O
+.	O
+22	O
++	O
+/	O
+-	O
+0	O
+.	O
+14	O
+and	O
+0	O
+.	O
+27	O
++	O
+/	O
+-	O
+0	O
+.	O
+07	O
+nmol	O
+/	O
+min	O
+/	O
+mg	O
+protein	O
+,	O
+respectively	O
+,	O
+in	O
+control	O
+subjects	O
+.	O
+
+The	O
+Myc	B-GENE
+LZ	I-GENE
+was	O
+found	O
+to	O
+prevent	O
+homodimeric	O
+interactions	O
+,	O
+thus	O
+explaining	O
+Myc	B-GENE
+inability	O
+to	O
+homodimerize	O
+efficiently	O
+.	O
+
+Thus	O
+,	O
+VF	O
+resistant	O
+to	O
+defibrillation	O
+is	O
+not	O
+necessarily	O
+associated	O
+with	O
+both	O
+toxic	O
+plasma	O
+drug	O
+level	O
+and	O
+remarkably	O
+decreased	O
+conduction	O
+.	O
+
+The	O
+smallest	O
+active	B-GENE
+FecR	I-GENE
+derivative	I-GENE
+contained	O
+59	O
+amino	O
+acid	O
+residues	O
+as	O
+compared	O
+to	O
+the	O
+317	O
+residues	O
+of	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+FecR	I-GENE
+.	O
+
+The	O
+gene	O
+pairs	O
+psbB	B-GENE
+-	O
+psbT	B-GENE
+and	O
+psbH	B-GENE
+-	O
+psbN	B-GENE
+are	O
+cotranscribed	O
+from	O
+opposite	O
+strands	O
+.	O
+
+The	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+contains	O
+regions	O
+identical	O
+to	O
+the	O
+sequences	O
+of	O
+peptides	O
+derived	O
+from	O
+bovine	B-GENE
+liver	I-GENE
+eIF	I-GENE
+-	I-GENE
+2B	I-GENE
+alpha	I-GENE
+subunit	I-GENE
+.	O
+
+Expression	O
+of	O
+this	O
+cDNA	O
+in	O
+vitro	O
+yields	O
+a	O
+peptide	O
+which	O
+comigrates	O
+with	O
+natural	B-GENE
+eIF	I-GENE
+-	I-GENE
+2B	I-GENE
+alpha	I-GENE
+in	O
+SDS	O
+/	O
+polyacrylamide	O
+gels	O
+.	O
+
+When	O
+RNA	O
+encoding	O
+the	O
+tail	O
+domain	O
+of	O
+desmoglein	B-GENE
+was	O
+coinjected	O
+with	O
+plakoglobin	B-GENE
+RNA	I-GENE
+,	O
+both	O
+the	O
+dorsalizing	O
+effect	O
+and	O
+nuclear	O
+accumulation	O
+of	O
+plakoglobin	B-GENE
+were	O
+suppressed	O
+.	O
+
+Six	O
+of	O
+them	O
+,	O
+NUC1	B-GENE
+,	O
+PRP21	B-GENE
+(	O
+also	O
+called	O
+SPP91	B-GENE
+)	O
+,	O
+CDC6	B-GENE
+,	O
+CRY2	B-GENE
+,	O
+the	O
+gene	O
+encoding	O
+the	O
+ribosomal	B-GENE
+protein	I-GENE
+S24	I-GENE
+and	O
+the	O
+gene	O
+coding	O
+for	O
+a	O
+hypothetical	O
+protein	O
+of	O
+599	O
+amino	O
+acids	O
+,	O
+have	O
+been	O
+sequenced	O
+previously	O
+.	O
+
+Intrastriatal	O
+grafts	O
+of	O
+nigral	O
+and	O
+adrenal	O
+tissues	O
+have	O
+been	O
+found	O
+to	O
+be	O
+effective	O
+in	O
+alleviating	O
+many	O
+of	O
+the	O
+simple	O
+motor	O
+and	O
+sensorimotor	O
+deficits	O
+associated	O
+with	O
+lesions	O
+of	O
+the	O
+nigrostriatal	O
+dopamine	O
+system	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+determine	O
+the	O
+impact	O
+of	O
+the	O
+introduction	O
+of	O
+clarithromycin	O
+and	O
+azithromycin	O
+on	O
+the	O
+treatment	O
+and	O
+survival	O
+of	O
+patients	O
+with	O
+AIDS	O
+and	O
+disseminated	O
+Mycobacterium	O
+avium	O
+complex	O
+(	O
+DMAC	O
+)	O
+.	O
+
+Thereafter	O
+,	O
+the	O
+aggregation	O
+rose	O
+to	O
+the	O
+initial	O
+100	O
+%	O
+value	O
+4	O
+h	O
+after	O
+drug	O
+application	O
+and	O
+remained	O
+at	O
+this	O
+level	O
+during	O
+the	O
+observation	O
+period	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Growth	O
+curves	O
+indicated	O
+that	O
+proliferation	O
+of	O
+clone	O
+CA9	O
+in	O
+the	O
+presence	O
+of	O
+10	O
+%	O
+serum	O
+was	O
+reduced	O
+by	O
+60	O
+%	O
+compared	O
+with	O
+clone	O
+ME10	O
+.	O
+
+The	O
+protein	O
+coding	O
+region	O
+,	O
+1	O
+,	O
+696	O
+bps	O
+long	O
+,	O
+is	O
+divided	O
+by	O
+an	O
+intron	O
+into	O
+two	O
+exons	O
+.	O
+
+The	O
+UAS	O
+of	O
+the	O
+AAC2	B-GENE
+gene	I-GENE
+contains	O
+at	O
+least	O
+two	O
+distinct	O
+motifs	O
+for	O
+DNA	O
+-	O
+binding	O
+transcriptional	O
+activators	O
+,	O
+including	O
+one	O
+which	O
+is	O
+identical	O
+with	O
+the	O
+core	O
+HAP2	B-GENE
+/	I-GENE
+3	I-GENE
+/	I-GENE
+4	I-GENE
+binding	I-GENE
+motif	I-GENE
+,	O
+and	O
+a	O
+second	O
+one	O
+with	O
+the	O
+ABF1	B-GENE
+consensus	I-GENE
+binding	I-GENE
+sequence	I-GENE
+.	O
+
+The	O
+emerging	O
+complexity	O
+of	O
+the	O
+5	O
+'	O
+regulatory	O
+region	O
+of	O
+the	O
+GH	B-GENE
+receptor	I-GENE
+gene	I-GENE
+was	O
+emphasised	O
+by	O
+the	O
+observation	O
+that	O
+probes	O
+derived	O
+from	O
+exon	O
+1B	O
+and	O
+the	O
+distal	O
+3	O
+'	O
+intron	O
+boundary	O
+do	O
+not	O
+hybridise	O
+with	O
+previously	O
+cloned	O
+genomic	O
+sequences	O
+that	O
+span	O
+the	O
+liver	O
+-	O
+specific	O
+P1	O
+promoter	O
+and	O
+exon	O
+2	O
+.	O
+
+A	O
+polymorphic	O
+dinucleotide	O
+(	O
+GT	O
+/	O
+CA	O
+)	O
+n	O
+repeat	O
+contained	O
+in	O
+the	O
+NHE5	O
+cosmid	O
+was	O
+identified	O
+and	O
+developed	O
+into	O
+a	O
+microsatellite	O
+PCR	O
+marker	O
+.	O
+
+The	O
+proteins	O
+are	O
+more	O
+than	O
+90	O
+%	O
+identical	O
+to	O
+each	O
+other	O
+within	O
+the	O
+protein	O
+kinase	O
+domain	O
+but	O
+only	O
+51	O
+-	O
+59	O
+%	O
+identical	O
+to	O
+other	O
+casein	B-GENE
+kinase	I-GENE
+I	I-GENE
+isoforms	I-GENE
+within	O
+this	O
+region	O
+.	O
+
+We	O
+used	O
+two	O
+approaches	O
+to	O
+ascertain	O
+whether	O
+CDP	B-GENE
+/	O
+cut	B-GENE
+serves	O
+as	O
+a	O
+repressor	O
+of	O
+gp91	B-GENE
+-	O
+phox	B-GENE
+gene	O
+expression	O
+.	O
+
+Despite	O
+the	O
+activation	O
+of	O
+these	O
+intracellular	O
+signaling	O
+molecules	O
+,	O
+PDGF	B-GENE
+beta	I-GENE
+receptor	I-GENE
+activation	O
+elicited	O
+no	O
+detectable	O
+effect	O
+on	O
+cell	O
+proliferation	O
+or	O
+differentiation	O
+.	O
+
+UAS1	O
+is	O
+the	O
+binding	O
+site	O
+for	O
+the	O
+transcriptional	O
+regulator	O
+Adr1p	B-GENE
+.	O
+
+In	O
+the	O
+context	O
+of	O
+the	O
+ADH2	B-GENE
+upstream	I-GENE
+regulatory	I-GENE
+region	I-GENE
+,	O
+including	O
+UAS1	O
+,	O
+working	O
+in	O
+concert	O
+with	O
+the	O
+ADH2	B-GENE
+basal	I-GENE
+promoter	I-GENE
+elements	I-GENE
+,	O
+UAS2	O
+-	O
+dependent	O
+gene	O
+activation	O
+was	O
+dependent	O
+on	O
+orientation	O
+,	O
+copy	O
+number	O
+,	O
+and	O
+helix	O
+phase	O
+.	O
+
+Induction	O
+in	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+DNA	O
+binding	O
+correlates	O
+with	O
+a	O
+concomitant	O
+GH	B-GENE
+trans	O
+-	O
+activation	O
+of	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+genes	I-GENE
+described	O
+previously	O
+.	O
+
+Inactivation	O
+of	O
+MAP	B-GENE
+kinases	I-GENE
+occurs	O
+via	O
+a	O
+specific	O
+phosphatase	O
+,	O
+MKP	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Short	O
+-	O
+course	O
+amphotericin	O
+B	O
+therapy	O
+for	O
+candidemia	O
+in	O
+pediatric	O
+patients	O
+.	O
+
+Furthermore	O
+,	O
+45Ca	O
+-	O
+binding	O
+assays	O
+revealed	O
+that	O
+CCaMK	B-GENE
+directly	O
+binds	O
+Ca2	O
++	O
+.	O
+
+The	O
+protein	O
+expressed	O
+from	O
+the	O
+cloned	O
+cDNA	O
+is	O
+secreted	O
+into	O
+the	O
+culture	O
+medium	O
+and	O
+yields	O
+of	O
+up	O
+to	O
+40	O
+mg	O
+per	O
+litre	O
+have	O
+been	O
+obtained	O
+.	O
+
+Plasmids	O
+pAMS12	O
+,	O
+pAMS13	O
+and	O
+pAMS14	O
+were	O
+transformed	O
+into	O
+a	O
+laboratory	O
+strain	O
+of	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+whereas	O
+pAMS15	O
+was	O
+stably	O
+introduced	O
+into	O
+two	O
+commercial	O
+wine	O
+yeast	O
+strains	O
+.	O
+
+The	O
+maximum	O
+induction	O
+of	O
+ACC	B-GENE
+-	I-GENE
+oxidase	I-GENE
+transcripts	I-GENE
+occurred	O
+at	O
+about	O
+6	O
+h	O
+after	O
+excision	O
+,	O
+while	O
+the	O
+maximum	O
+enzyme	O
+activity	O
+was	O
+observed	O
+at	O
+24	O
+h	O
+.	O
+
+Within	O
+their	O
+polypeptide	O
+chain	O
+,	O
+they	O
+all	O
+contain	O
+those	O
+conserved	O
+features	O
+that	O
+define	O
+a	O
+plant	O
+CDPK	B-GENE
+;	O
+kinase	O
+catalytic	O
+sequences	O
+are	O
+linked	O
+to	O
+a	O
+calmodulin	B-GENE
+-	I-GENE
+like	I-GENE
+regulatory	I-GENE
+domain	I-GENE
+through	O
+a	O
+junction	O
+region	O
+.	O
+
+Repair	O
+of	O
+this	O
+insertion	O
+by	O
+homologous	O
+recombination	O
+restores	O
+the	O
+activity	O
+of	O
+the	O
+hprt	B-GENE
+locus	I-GENE
+,	O
+thus	O
+confirming	O
+the	O
+site	O
+of	O
+mutation	O
+.	O
+
+The	O
+timing	O
+of	O
+fla	B-GENE
+gene	I-GENE
+expression	O
+in	O
+the	O
+cell	O
+cycle	O
+is	O
+determined	O
+by	O
+specialized	O
+forms	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+and	O
+the	O
+appearance	O
+and	O
+/	O
+or	O
+activation	O
+of	O
+regulatory	O
+proteins	O
+.	O
+
+Primer	O
+extension	O
+experiments	O
+revealed	O
+a	O
+strong	O
+transcription	O
+initiation	O
+site	O
+102	O
+bp	O
+upstream	O
+of	O
+the	O
+translational	O
+start	O
+site	O
+.	O
+
+Polypeptides	O
+of	O
+the	O
+same	O
+apparent	O
+sizes	O
+are	O
+detected	O
+in	O
+spores	O
+of	O
+a	O
+cotE	B-GENE
+null	O
+mutant	O
+,	O
+on	O
+which	O
+basis	O
+we	O
+infer	O
+that	O
+the	O
+products	O
+of	O
+the	O
+cotJ	B-GENE
+operon	I-GENE
+are	O
+required	O
+for	O
+the	O
+normal	O
+formation	O
+of	O
+the	O
+inner	O
+layers	O
+of	O
+the	O
+coat	O
+or	O
+are	O
+themselves	O
+structural	O
+components	O
+of	O
+the	O
+coat	O
+.	O
+
+Based	O
+on	O
+the	O
+estimated	O
+values	O
+of	O
+divergence	O
+of	O
+apobec1	B-GENE
+sequences	I-GENE
+in	O
+terms	O
+of	O
+the	O
+numbers	O
+of	O
+synonymous	O
+and	O
+non	O
+-	O
+synonymous	O
+suhstitutions	O
+per	O
+site	O
+,	O
+we	O
+found	O
+that	O
+apobec1	B-GENE
+is	O
+a	O
+fairly	O
+rapidly	O
+evolving	O
+protein	O
+.	O
+
+EEA1	B-GENE
+is	O
+a	O
+conserved	O
+alpha	O
+-	O
+helical	O
+peripheral	O
+membrane	O
+protein	O
+flanked	O
+by	O
+cysteine	O
+"	O
+fingers	O
+"	O
+and	O
+contains	O
+a	O
+calmodulin	B-GENE
+-	I-GENE
+binding	I-GENE
+IQ	I-GENE
+motif	I-GENE
+.	O
+
+Nucleotide	O
+sequences	O
+of	O
+the	O
+clones	O
+revealed	O
+that	O
+one	O
+clone	O
+,	O
+cap3	B-GENE
+,	O
+contained	O
+an	O
+open	O
+reading	O
+frame	O
+(	O
+ORF	O
+)	O
+that	O
+would	O
+code	O
+for	O
+a	O
+26	O
+-	O
+amino	O
+acid	O
+,	O
+cysteine	O
+-	O
+rich	O
+peptide	O
+with	O
+significant	O
+homology	O
+to	O
+Neurospora	B-GENE
+crassa	I-GENE
+copper	I-GENE
+metallothionein	I-GENE
+.	O
+
+Sensing	O
+with	O
+chemically	O
+and	O
+biologically	O
+modified	O
+carbon	O
+electrodes	O
+.	O
+
+Elevation	O
+of	O
+the	O
+tissues	O
+of	O
+the	O
+face	O
+is	O
+essentially	O
+vertical	O
+and	O
+acts	O
+on	O
+the	O
+forehead	O
+,	O
+temporal	O
+region	O
+,	O
+gaze	O
+and	O
+cheekbones	O
+.	O
+
+This	O
+region	O
+binds	O
+two	O
+ubiquitous	O
+nuclear	O
+factors	O
+,	O
+USF	B-GENE
+/	O
+MLTF	B-GENE
+and	O
+the	O
+CAAT	B-GENE
+-	I-GENE
+binding	I-GENE
+transcription	I-GENE
+factor	I-GENE
+/	O
+nuclear	B-GENE
+factor	I-GENE
+1	I-GENE
+(	O
+CTF	B-GENE
+/	O
+NF1	B-GENE
+)	O
+.	O
+
+The	O
+potential	O
+impact	O
+of	O
+using	O
+a	O
+rapid	O
+diagnostic	O
+test	O
+(	O
+Strep	O
+A	O
+OIA	O
+)	O
+on	O
+detection	O
+and	O
+treatment	O
+of	O
+group	O
+A	O
+beta	O
+-	O
+hemolytic	O
+streptococcal	O
+(	O
+GABHS	O
+)	O
+pharyngitis	O
+in	O
+a	O
+large	O
+-	O
+volume	O
+pediatric	O
+and	O
+adolescent	O
+clinic	O
+was	O
+examined	O
+.	O
+
+The	O
+bHLH	B-GENE
+proteins	I-GENE
+function	O
+as	O
+potent	O
+transcriptional	O
+activators	O
+of	O
+tissue	O
+-	O
+specific	O
+genes	O
+by	O
+forming	O
+heterodimers	O
+between	O
+ubiquitous	O
+and	O
+cell	O
+-	O
+restricted	O
+family	O
+members	O
+.	O
+
+YAC	O
+and	O
+cosmid	O
+contigs	O
+spanning	O
+the	O
+BRCA1	B-GENE
+region	I-GENE
+were	O
+used	O
+to	O
+select	O
+cDNA	O
+clones	O
+from	O
+pools	O
+of	O
+cDNAs	O
+derived	O
+from	O
+human	O
+placenta	O
+,	O
+HeLa	O
+cells	O
+,	O
+activated	O
+T	O
+cells	O
+,	O
+and	O
+fetal	O
+head	O
+.	O
+
+This	O
+study	O
+assesses	O
+the	O
+feasibility	O
+and	O
+toxicity	O
+of	O
+adoptive	O
+immunotherapy	O
+with	O
+tumor	O
+infiltrating	O
+lymphocytes	O
+and	O
+recombinant	B-GENE
+interleukin	I-GENE
+-	I-GENE
+2	I-GENE
+in	O
+29	O
+patients	O
+who	O
+underwent	O
+resection	O
+for	O
+stage	O
+III	O
+non	O
+-	O
+small	O
+-	O
+cell	O
+lung	O
+cancer	O
+.	O
+
+The	O
+present	O
+study	O
+describes	O
+the	O
+cell	O
+volume	O
+dynamics	O
+in	O
+intact	O
+rat	O
+hearts	O
+,	O
+during	O
+ischemia	O
+and	O
+after	O
+reperfusion	O
+.	O
+
+In	O
+contrast	O
+,	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+alone	O
+had	O
+no	O
+effect	O
+on	O
+repCRS2	O
+-	O
+dependent	O
+reporter	O
+gene	O
+activity	O
+.	O
+
+DNA	O
+sequencing	O
+and	O
+Southern	O
+blot	O
+analyses	O
+established	O
+that	O
+the	O
+cDNA	O
+clones	O
+are	O
+derived	O
+from	O
+two	O
+different	O
+genes	O
+.	O
+
+Mutation	O
+of	O
+the	O
+Sp1	B-GENE
+element	I-GENE
+,	O
+which	O
+abolishes	O
+Sp1	B-GENE
+binding	O
+,	O
+results	O
+in	O
+a	O
+6	O
+-	O
+10	O
+-	O
+fold	O
+reduction	O
+in	O
+reporter	O
+activity	O
+.	O
+
+The	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+is	O
+overexpressed	O
+in	O
+a	O
+variety	O
+of	O
+tumor	O
+types	O
+and	O
+appears	O
+to	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+abnormal	O
+growth	O
+of	O
+a	O
+number	O
+of	O
+cell	O
+types	O
+.	O
+
+Schooling	O
+is	O
+found	O
+to	O
+be	O
+related	O
+to	O
+good	O
+health	O
+even	O
+after	O
+controlling	O
+for	O
+differences	O
+in	O
+observable	O
+health	O
+inputs	O
+.	O
+
+With	O
+this	O
+bisected	O
+diastolic	O
+driving	O
+,	O
+the	O
+abnormal	O
+echo	O
+disappeared	O
+completely	O
+.	O
+
+It	O
+acts	O
+on	O
+Cdks	B-GENE
+in	O
+the	O
+G1	O
+and	O
+S	O
+phases	O
+of	O
+the	O
+cell	O
+cycle	O
+,	O
+and	O
+also	O
+binds	O
+to	O
+proliferating	B-GENE
+cell	I-GENE
+nuclear	I-GENE
+antigen	I-GENE
+(	O
+PCNA	B-GENE
+)	O
+,	O
+blocking	O
+DNA	O
+replication	O
+in	O
+vitro	O
+.	O
+
+Two	O
+major	O
+and	O
+one	O
+minor	O
+transcription	O
+initiation	O
+sites	O
+were	O
+assigned	O
+to	O
+positions	O
++	O
+1	O
+and	O
++	O
+24	O
+and	O
+position	O
++	O
+14	O
+,	O
+respectively	O
+,	O
+by	O
+a	O
+combination	O
+of	O
+ribonuclease	O
+protection	O
+,	O
+primer	O
+extension	O
+,	O
+and	O
+5	O
+'	O
+RACE	O
+analyses	O
+.	O
+
+Further	O
+,	O
+the	O
+ORFs	O
+of	O
+components	O
+3	O
+and	O
+5	O
+potentially	O
+encoded	O
+proteins	O
+of	O
+about	O
+20	O
+kDa	O
+,	O
+the	O
+size	O
+of	O
+the	O
+BBTV	B-GENE
+coat	I-GENE
+protein	I-GENE
+.	O
+
+CodY	B-GENE
+does	O
+not	O
+have	O
+any	O
+homologues	O
+in	O
+the	O
+data	O
+-	O
+bases	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+investigate	O
+the	O
+incidence	O
+and	O
+presentation	O
+of	O
+acute	O
+pernicious	O
+or	O
+fulminating	O
+beriberi	O
+in	O
+a	O
+general	O
+district	O
+hospital	O
+.	O
+
+Unlike	O
+most	O
+other	O
+small	B-GENE
+G	I-GENE
+proteins	I-GENE
+which	O
+are	O
+expressed	O
+ubiquitously	O
+,	O
+TTF	B-GENE
+was	O
+transcribed	O
+only	O
+in	O
+hemopoietic	O
+cells	O
+as	O
+a	O
+2	O
+.	O
+2	O
+kb	O
+transcript	O
+.	O
+
+An	O
+explanation	O
+explored	O
+for	O
+this	O
+lack	O
+of	O
+gene	O
+expression	O
+was	O
+that	O
+increased	O
+levels	O
+of	O
+RAR	B-GENE
+alpha	I-GENE
+or	O
+PML	B-GENE
+might	O
+suppress	O
+APL	O
+cell	O
+growth	O
+.	O
+
+Cytosolic	O
+extracts	O
+from	O
+a	O
+variety	O
+of	O
+mammalian	O
+cell	O
+lines	O
+(	O
+monkey	O
+Cos7	O
+,	O
+several	O
+mouse	O
+fibrosarcomas	O
+and	O
+human	O
+HeLa	O
+S3	O
+)	O
+demonstrated	O
+similar	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+1	I-GENE
+dependent	O
+RNA	O
+-	O
+protein	O
+band	O
+shifts	O
+as	O
+cell	O
+extract	O
+from	O
+BALB	O
+/	O
+c	O
+3T3	O
+mouse	O
+fibroblasts	O
+.	O
+
+The	O
+provisional	O
+reports	O
+are	O
+based	O
+mainly	O
+upon	O
+macroscopic	O
+findings	O
+,	O
+whereas	O
+the	O
+final	O
+reports	O
+include	O
+the	O
+information	O
+provided	O
+by	O
+supplementary	O
+investigations	O
+such	O
+as	O
+microscopy	O
+,	O
+histochemistry	O
+,	O
+more	O
+rarely	O
+electron	O
+microscopy	O
+,	O
+immunohistochemistry	O
+and	O
+/	O
+or	O
+microbiology	O
+.	O
+
+Circulating	O
+thrombomodulin	B-GENE
+:	O
+current	O
+knowledge	O
+and	O
+future	O
+prospects	O
+
+CPT	O
+-	O
+11	O
+was	O
+administered	O
+as	O
+a	O
+30	O
+-	O
+minute	O
+i	O
+.	O
+v	O
+.	O
+infusion	O
+at	O
+a	O
+dose	O
+of	O
+350	O
+mg	O
+/	O
+m2	O
+diluted	O
+in	O
+250	O
+ml	O
+normal	O
+saline	O
+every	O
+3	O
+weeks	O
+.	O
+
+A	O
+73	O
+bp	O
+fragment	O
+(	O
+X1	O
+region	O
+)	O
+of	O
+the	O
+PRB	B-GENE
+-	I-GENE
+1b	I-GENE
+promoter	I-GENE
+,	O
+located	O
+between	O
+positions	O
+-	O
+213	O
+and	O
+-	O
+141	O
+,	O
+was	O
+sufficient	O
+to	O
+confer	O
+ethylene	O
+responsiveness	O
+to	O
+the	O
+reporter	O
+gene	O
+.	O
+
+To	O
+assess	O
+the	O
+function	O
+(	O
+s	O
+)	O
+of	O
+E74	B-GENE
+during	O
+metamorphosis	O
+,	O
+we	O
+have	O
+isolated	O
+and	O
+characterized	O
+recessive	O
+loss	O
+-	O
+of	O
+-	O
+function	O
+mutations	O
+specific	O
+to	O
+each	O
+transcription	O
+unit	O
+.	O
+
+Although	O
+the	O
+extracellular	O
+domain	O
+of	O
+the	O
+TSH	B-GENE
+-	I-GENE
+R	I-GENE
+is	O
+sufficient	O
+for	O
+high	O
+affinity	O
+binding	O
+of	O
+TSH	B-GENE
+,	O
+we	O
+conclude	O
+that	O
+the	O
+hyt	O
+mutation	O
+in	O
+the	O
+fourth	O
+transmembrane	O
+domain	O
+eliminates	O
+TSH	B-GENE
+binding	O
+.	O
+
+Lipiodol	O
+was	O
+covalently	O
+conjugated	O
+with	O
+EDTB	O
+.	O
+
+Moreover	O
+,	O
+Western	O
+blots	O
+demonstrated	O
+at	O
+least	O
+six	O
+types	O
+of	O
+Ypt	B-GENE
+in	O
+both	O
+Cr	O
+and	O
+Vc	O
+,	O
+suggesting	O
+that	O
+these	O
+Ypt	B-GENE
+are	O
+used	O
+for	O
+household	O
+functions	O
+responsible	O
+for	O
+vesicle	O
+transport	O
+rather	O
+than	O
+for	O
+cellular	O
+differentiation	O
+.	O
+
+The	O
+absence	O
+of	O
+other	O
+regions	O
+of	O
+hybridization	O
+suggests	O
+that	O
+there	O
+are	O
+no	O
+closely	O
+related	O
+sequences	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+reverse	O
+transcribed	O
+pseudogenes	O
+)	O
+scattered	O
+throughout	O
+the	O
+genome	O
+and	O
+that	O
+if	O
+there	O
+are	O
+closely	O
+related	O
+genes	O
+,	O
+they	O
+must	O
+be	O
+clustered	O
+near	O
+GSTT2	B-GENE
+.	O
+
+However	O
+,	O
+the	O
+lens	O
+dose	O
+(	O
+3	O
+.	O
+6	O
+Gy	O
+/	O
+25	O
+fractions	O
+)	O
+was	O
+higher	O
+compared	O
+to	O
+the	O
+other	O
+techniques	O
+.	O
+
+Antibodies	O
+to	O
+the	O
+human	B-GENE
+PTS1R	I-GENE
+recognize	O
+this	O
+protein	O
+in	O
+human	O
+,	O
+monkey	O
+,	O
+rat	O
+,	O
+and	O
+hamster	O
+cells	O
+.	O
+
+There	O
+is	O
+a	O
+national	O
+effort	O
+to	O
+begin	O
+to	O
+ask	O
+all	O
+female	O
+patients	O
+about	O
+family	O
+violence	O
+.	O
+
+GnRH	B-GENE
+treatment	O
+was	O
+found	O
+to	O
+increase	O
+the	O
+phosphorylation	O
+of	O
+tyrosine	O
+residues	O
+of	O
+MAPK	B-GENE
+and	O
+to	O
+increase	O
+MAPK	B-GENE
+activity	O
+,	O
+as	O
+determined	O
+by	O
+an	O
+immune	O
+complex	O
+kinase	O
+assay	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+an	O
+amphibian	B-GENE
+insulin	I-GENE
+receptor	I-GENE
+substrate	I-GENE
+1	I-GENE
+-	I-GENE
+like	I-GENE
+cDNA	I-GENE
+and	O
+involvement	O
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+in	O
+insulin	B-GENE
+-	O
+induced	O
+Xenopus	O
+oocyte	O
+maturation	O
+.	O
+
+We	O
+report	O
+here	O
+that	O
+in	O
+cultured	O
+Jurkat	O
+T	O
+cells	O
+,	O
+Cbl	B-GENE
+is	O
+coprecipitated	O
+with	O
+antibody	O
+against	O
+the	O
+adapter	B-GENE
+protein	I-GENE
+Grb2	I-GENE
+.	O
+
+The	O
+effect	O
+of	O
+these	O
+cell	O
+cycle	O
+regulators	O
+is	O
+not	O
+specific	O
+to	O
+the	O
+rap1s	B-GENE
+or	O
+hmr	B-GENE
+delta	I-GENE
+A	I-GENE
+mutation	I-GENE
+,	O
+since	O
+swi6	B-GENE
+,	O
+swi4	B-GENE
+,	O
+and	O
+clb5	B-GENE
+mutations	I-GENE
+also	O
+suppress	O
+mutations	O
+in	O
+SIR1	B-GENE
+,	O
+another	O
+gene	O
+implicated	O
+in	O
+the	O
+establishment	O
+of	O
+silencing	O
+.	O
+
+ICP4	B-GENE
+has	O
+been	O
+shown	O
+to	O
+form	O
+tripartite	O
+complexes	O
+cooperatively	O
+with	O
+the	O
+TATA	B-GENE
+box	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+and	O
+TFIIB	B-GENE
+on	O
+DNA	O
+containing	O
+an	O
+ICP4	B-GENE
+binding	I-GENE
+site	I-GENE
+and	O
+a	O
+TATA	O
+box	O
+(	O
+C	O
+.	O
+
+Characterization	O
+of	O
+fus1	B-GENE
+of	O
+Schizosaccharomyces	O
+pombe	O
+:	O
+a	O
+developmentally	O
+controlled	O
+function	O
+needed	O
+for	O
+conjugation	O
+.	O
+
+SRY	B-GENE
+-	I-GENE
+related	I-GENE
+cDNA	I-GENE
+encoding	O
+a	O
+protein	O
+with	O
+a	O
+high	B-GENE
+-	I-GENE
+mobility	I-GENE
+-	I-GENE
+group	I-GENE
+(	O
+HMG	B-GENE
+)	O
+box	O
+and	O
+a	O
+leucine	O
+zipper	O
+motif	O
+,	O
+which	O
+was	O
+designated	O
+SOX	B-GENE
+-	I-GENE
+LZ	I-GENE
+,	O
+was	O
+isolated	O
+from	O
+a	O
+rainbow	O
+trout	O
+testis	O
+cDNA	O
+library	O
+.	O
+
+Scalp	O
+flaps	O
+can	O
+be	O
+expanded	O
+just	O
+to	O
+the	O
+point	O
+of	O
+becoming	O
+noticeable	O
+over	O
+4	O
+to	O
+6	O
+weeks	O
+followed	O
+by	O
+scalp	O
+flap	O
+transposition	O
+and	O
+easy	O
+closure	O
+of	O
+the	O
+donor	O
+site	O
+.	O
+
+In	O
+the	O
+Center	O
+for	O
+Human	O
+Genetics	O
+in	O
+Leuven	O
+,	O
+predictive	O
+DNA	O
+-	O
+testing	O
+for	O
+Huntington	O
+'	O
+s	O
+disease	O
+is	O
+available	O
+as	O
+a	O
+clinical	O
+service	O
+since	O
+November	O
+1987	O
+,	O
+initially	O
+by	O
+DNA	O
+-	O
+linkage	O
+and	O
+since	O
+mid	O
+1993	O
+by	O
+direct	O
+mutation	O
+analysis	O
+.	O
+
+Risks	O
+of	O
+chronicity	O
+following	O
+acute	O
+hepatitis	O
+B	O
+virus	O
+infection	O
+:	O
+a	O
+review	O
+.	O
+
+Examination	O
+of	O
+neurohumoral	O
+factors	O
+revealed	O
+a	O
+hyperactive	O
+sympathetic	O
+nervous	O
+system	O
+and	O
+an	O
+increase	O
+in	O
+plasma	O
+renin	B-GENE
+activity	O
+.	O
+
+We	O
+compared	O
+the	O
+inhibitory	O
+effect	O
+of	O
+naturally	O
+occurring	O
+mutant	B-GENE
+hTR	I-GENE
+beta	I-GENE
+1	I-GENE
+,	O
+artificially	O
+created	O
+hTR	B-GENE
+alpha	I-GENE
+1	I-GENE
+mutants	I-GENE
+,	O
+c	B-GENE
+-	I-GENE
+erbA	I-GENE
+alpha	I-GENE
+2	I-GENE
+and	O
+the	O
+human	B-GENE
+peroxisome	I-GENE
+proliferator	I-GENE
+-	I-GENE
+activated	I-GENE
+receptor	I-GENE
+(	O
+hPPAR	B-GENE
+)	O
+on	O
+three	O
+prototypic	O
+T3	O
+-	O
+response	O
+elements	O
+(	O
+TREs	O
+)	O
+,	O
+TRE	O
+-	O
+PAL	O
+,	O
+DR	O
++	O
+4	O
+and	O
+TRE	O
+-	O
+LAP	O
+.	O
+
+The	O
+amino	O
+-	O
+terminal	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+Pip	B-GENE
+exhibits	O
+a	O
+high	O
+degree	O
+of	O
+homology	O
+to	O
+the	O
+DNA	O
+-	O
+binding	O
+domains	O
+of	O
+members	O
+of	O
+the	O
+interferon	B-GENE
+regulatory	I-GENE
+factor	I-GENE
+(	O
+IRF	B-GENE
+)	O
+family	O
+,	O
+which	O
+includes	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+ICSBP	B-GENE
+,	O
+and	O
+ISGF3	B-GENE
+gamma	I-GENE
+.	O
+
+An	O
+outbreak	O
+of	O
+hepatitis	O
+A	O
+among	O
+homosexual	O
+men	O
+in	O
+Amsterdam	O
+,	O
+1991	O
+-	O
+1993	O
+.	O
+
+The	O
+RAP74	B-GENE
+subunit	I-GENE
+of	O
+TFIIF	B-GENE
+alone	O
+contained	O
+the	O
+stimulatory	O
+activity	O
+and	O
+the	O
+minimal	O
+region	O
+sufficient	O
+for	O
+stimulation	O
+corresponds	O
+to	O
+COOH	O
+-	O
+terminal	O
+residues	O
+358	O
+-	O
+517	O
+.	O
+
+We	O
+have	O
+generated	O
+various	O
+base	O
+substitutions	O
+and	O
+internal	O
+deletions	O
+in	O
+and	O
+around	O
+DRE	O
+(	O
+nucleotide	O
+positions	O
+-	O
+93	O
+to	O
+-	O
+100	O
+with	O
+respect	O
+to	O
+the	O
+transcription	O
+initiation	O
+site	O
+)	O
+of	O
+the	O
+PCNA	B-GENE
+gene	I-GENE
+in	O
+vitro	O
+and	O
+subsequently	O
+examined	O
+their	O
+effects	O
+on	O
+the	O
+binding	O
+to	O
+DREF	B-GENE
+(	O
+DRE	B-GENE
+-	I-GENE
+binding	I-GENE
+factor	I-GENE
+)	O
+and	O
+PCNA	B-GENE
+gene	I-GENE
+promote	O
+activity	O
+in	O
+cultured	O
+Drosophila	O
+Kc	O
+cells	O
+as	O
+well	O
+as	O
+in	O
+living	O
+flies	O
+.	O
+
+The	O
+hsp70	B-GENE
+gene	I-GENE
+family	I-GENE
+of	O
+Neurospora	O
+crassa	O
+:	O
+cloning	O
+,	O
+sequence	O
+analysis	O
+,	O
+expression	O
+,	O
+and	O
+genetic	O
+mapping	O
+of	O
+the	O
+major	O
+stress	O
+-	O
+inducible	O
+member	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequences	O
+of	O
+each	O
+of	O
+the	O
+W3A1	B-GENE
+ETF	I-GENE
+subunits	I-GENE
+exhibit	O
+only	O
+approximately	O
+30	O
+%	O
+identity	O
+with	O
+the	O
+corresponding	O
+subunits	O
+of	O
+the	O
+ETF	B-GENE
+from	O
+human	O
+,	O
+rat	O
+,	O
+and	O
+Paracoccus	O
+denitrificans	O
+,	O
+which	O
+as	O
+a	O
+group	O
+are	O
+greater	O
+than	O
+50	O
+%	O
+identical	O
+.	O
+
+This	O
+last	O
+region	O
+contains	O
+two	O
+sites	O
+that	O
+bind	O
+Ets	B-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+present	O
+in	O
+liver	O
+nuclear	O
+extracts	O
+as	O
+well	O
+as	O
+recombinant	B-GENE
+purified	I-GENE
+Ets	I-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+.	O
+
+Other	O
+assays	O
+also	O
+distinguished	O
+the	O
+processive	O
+replication	O
+of	O
+pNeo	O
+.	O
+Myc	O
+-	O
+2	O
+.	O
+4	O
+from	O
+the	O
+dispersive	O
+labeling	O
+of	O
+control	O
+plasmids	O
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+hoped	O
+that	O
+by	O
+defining	O
+the	O
+transcriptional	O
+control	O
+of	O
+the	O
+L7	B-GENE
+gene	I-GENE
+insights	O
+into	O
+the	O
+mechanisms	O
+that	O
+control	O
+functional	O
+fate	O
+and	O
+organization	O
+in	O
+the	O
+nervous	O
+system	O
+can	O
+be	O
+gained	O
+.	O
+
+In	O
+contrast	O
+,	O
+a	O
+Maf	B-GENE
+-	I-GENE
+related	I-GENE
+protein	I-GENE
+,	O
+Nrl	B-GENE
+,	O
+completely	O
+mimicked	O
+c	B-GENE
+-	I-GENE
+Maf	I-GENE
+actions	O
+.	O
+
+The	O
+27	O
+-	O
+base	O
+element	O
+interacts	O
+with	O
+a	O
+PDGF	B-GENE
+-	O
+activated	O
+serine	O
+/	O
+threonine	O
+phosphoprotein	O
+that	O
+is	O
+detected	O
+only	O
+within	O
+the	O
+nucleus	O
+of	O
+PDGF	O
+-	O
+treated	O
+3T3	O
+cells	O
+.	O
+
+By	O
+contrast	O
+,	O
+deletion	O
+of	O
+this	O
+Ras	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+did	O
+not	O
+diminish	O
+activation	O
+of	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+kinase	I-GENE
+by	O
+Src	B-GENE
+,	O
+implying	O
+that	O
+Src	B-GENE
+and	O
+Ras	B-GENE
+can	O
+activate	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+through	O
+independent	O
+mechanisms	O
+.	O
+
+In	O
+studies	O
+of	O
+many	O
+different	O
+phenotypically	O
+distinct	O
+cells	O
+,	O
+the	O
+CRE	O
+of	O
+the	O
+somatostatin	B-GENE
+gene	I-GENE
+promoter	I-GENE
+is	O
+a	O
+prototype	O
+of	O
+a	O
+highly	O
+cAMP	O
+-	O
+responsive	O
+element	O
+regulated	O
+by	O
+CREB	B-GENE
+.	O
+
+The	O
+first	O
+gene	O
+,	O
+NSR1	B-GENE
+,	O
+a	O
+previously	O
+identified	O
+gene	O
+,	O
+encodes	O
+a	O
+protein	O
+involved	O
+in	O
+ribosomal	O
+RNA	O
+maturation	O
+and	O
+possibly	O
+in	O
+transport	O
+of	O
+proteins	O
+into	O
+the	O
+nucleus	O
+.	O
+
+Characterization	O
+of	O
+the	O
+promoter	O
+for	O
+the	O
+human	B-GENE
+85	I-GENE
+kDa	I-GENE
+cytosolic	I-GENE
+phospholipase	I-GENE
+A2	I-GENE
+gene	I-GENE
+.	O
+
+This	O
+paper	O
+describes	O
+the	O
+advantages	O
+and	O
+limitations	O
+of	O
+the	O
+main	O
+study	O
+approaches	O
+used	O
+.	O
+
+Comparative	O
+study	O
+of	O
+the	O
+differential	O
+white	O
+blood	O
+cell	O
+count	O
+using	O
+three	O
+automated	O
+analyzers	O
+:	O
+Coulter	O
+STKS	O
+,	O
+Sysmex	O
+NE	O
+8000	O
+and	O
+Technicon	O
+H	O
+-	O
+1	O
+.	O
+
+Characterization	O
+of	O
+FIII	B-GENE
+/	O
+YY1	B-GENE
+,	O
+a	O
+Xenopus	B-GENE
+laevis	I-GENE
+conserved	I-GENE
+zinc	I-GENE
+-	I-GENE
+finger	I-GENE
+protein	I-GENE
+binding	O
+to	O
+the	O
+first	O
+exon	O
+of	O
+L1	B-GENE
+and	O
+L14	B-GENE
+ribosomal	I-GENE
+protein	I-GENE
+genes	I-GENE
+.	O
+
+Further	O
+studies	O
+established	O
+that	O
+the	O
+Ep	B-GENE
+-	O
+induced	O
+increase	O
+in	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+mRNA	I-GENE
+could	O
+be	O
+inhibited	O
+by	O
+the	O
+tyrosine	B-GENE
+kinase	I-GENE
+inhibitor	O
+genistein	O
+and	O
+the	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+inhibitor	O
+Compound	O
+3	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+This	O
+structure	O
+of	O
+cucumisin	B-GENE
+suggests	O
+that	O
+it	O
+is	O
+probably	O
+synthesized	O
+as	O
+an	O
+inactive	O
+precursor	O
+.	O
+
+Molecular	O
+dissection	O
+of	O
+the	O
+multimeric	O
+CD3	B-GENE
+-	O
+TCR	B-GENE
+complex	O
+revealed	O
+that	O
+at	O
+least	O
+two	O
+associated	O
+polypeptides	O
+,	O
+CD3	B-GENE
+zeta	I-GENE
+and	O
+CD3	B-GENE
+epsilon	I-GENE
+,	O
+autonomously	O
+couple	O
+antigenic	O
+recognition	O
+event	O
+to	O
+early	O
+and	O
+late	O
+events	O
+of	O
+the	O
+intracytoplasmic	O
+activation	O
+cascade	O
+.	O
+
+This	O
+study	O
+investigated	O
+the	O
+degree	O
+to	O
+which	O
+racial	O
+identity	O
+influences	O
+Mexican	O
+-	O
+Americans	O
+'	O
+performance	O
+on	O
+the	O
+L	O
+,	O
+K	O
+,	O
+and	O
+MF	O
+scales	O
+of	O
+the	O
+MMPI	O
+-	O
+2	O
+.	O
+
+Both	O
+can	O
+be	O
+elevated	O
+on	O
+a	O
+single	O
+vascular	O
+pedicle	O
+based	O
+on	O
+the	O
+superficial	O
+temporal	O
+artery	O
+,	O
+the	O
+double	O
+-	O
+layered	O
+temporal	O
+fascia	O
+flap	O
+.	O
+
+To	O
+do	O
+this	O
+,	O
+segments	O
+of	O
+DNA	O
+from	O
+the	O
+5	O
+'	O
+flank	O
+of	O
+the	O
+initiation	O
+sites	O
+for	O
+germline	O
+epsilon	O
+RNA	O
+were	O
+ligated	O
+to	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+and	O
+transfected	O
+into	O
+two	O
+mouse	O
+B	O
+cell	O
+lines	O
+,	O
+one	O
+of	O
+which	O
+can	O
+be	O
+induced	O
+to	O
+switch	O
+to	O
+IgE	B-GENE
+.	O
+
+The	O
+negative	O
+predictive	O
+value	O
+is	O
+92	O
+%	O
+,	O
+vs	O
+80	O
+%	O
+for	O
+the	O
+NCEP	O
+I	O
+.	O
+
+Oncogenic	O
+capacity	O
+of	O
+the	O
+E2F1	B-GENE
+gene	I-GENE
+.	O
+
+In	O
+some	O
+of	O
+the	O
+cases	O
+of	O
+solitary	O
+lesion	O
+,	O
+serum	B-GENE
+TSH	I-GENE
+levels	O
+,	O
+serum	B-GENE
+thyroglobulin	I-GENE
+values	O
+,	O
+and	O
+131I	O
+protein	O
+bounded	O
+iodine	O
+(	O
+131I	O
+-	O
+PBI	O
+)	O
+were	O
+measured	O
+,	O
+but	O
+there	O
+were	O
+no	O
+significant	O
+differences	O
+between	O
+successful	O
+and	O
+unsuccessful	O
+therapy	O
+.	O
+
+Endo16	B-GENE
+transcripts	I-GENE
+are	O
+confined	O
+to	O
+the	O
+definitive	O
+vegetal	O
+plate	O
+in	O
+blastula	O
+stage	O
+embryos	O
+;	O
+at	O
+gastrula	O
+stage	O
+this	O
+gene	O
+is	O
+expressed	O
+throughout	O
+the	O
+archenteron	O
+,	O
+but	O
+later	O
+only	O
+in	O
+the	O
+midgut	O
+.	O
+
+A	O
+unique	O
+leucine	O
+-	O
+proline	O
+repeat	O
+element	O
+found	O
+N	O
+-	O
+terminal	O
+to	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+EmBP	B-GENE
+-	I-GENE
+1	I-GENE
+does	O
+not	O
+appear	O
+to	O
+play	O
+a	O
+role	O
+in	O
+DNA	O
+-	O
+binding	O
+or	O
+dimerization	O
+.	O
+
+Another	O
+full	O
+ORF	O
+was	O
+found	O
+on	O
+the	O
+opposite	O
+strand	O
+downstream	O
+from	O
+the	O
+nspC	B-GENE
+gene	I-GENE
+.	O
+
+Two	O
+related	O
+cDNAs	O
+were	O
+isolated	O
+that	O
+encode	O
+proteins	O
+that	O
+recognize	O
+the	O
+XMyoDa	B-GENE
+TATA	I-GENE
+motif	I-GENE
+.	O
+
+Deletion	O
+of	O
+both	O
+prfA	B-GENE
+and	O
+ponA	B-GENE
+resulted	O
+in	O
+extremely	O
+slow	O
+growth	O
+and	O
+a	O
+reduction	O
+in	O
+sporulation	O
+efficiency	O
+.	O
+
+In	O
+broken	O
+L	O
+-	O
+cell	O
+membranes	O
+expressing	O
+wild	O
+type	O
+or	O
+mutant	B-GENE
+M6P	I-GENE
+/	I-GENE
+IGF	I-GENE
+II	I-GENE
+receptors	I-GENE
+,	O
+30	O
+nM	O
+IGF	B-GENE
+II	I-GENE
+also	O
+failed	O
+to	O
+affect	O
+the	O
+pertussis	B-GENE
+toxin	I-GENE
+substrate	O
+activity	O
+.	O
+
+Chem	O
+.	O
+
+For	O
+the	O
+first	O
+time	O
+we	O
+describe	O
+deletion	O
+and	O
+point	O
+mutations	O
+within	O
+the	O
+plasma	B-GENE
+membrane	I-GENE
+family	I-GENE
+of	I-GENE
+guanylyl	I-GENE
+cyclase	I-GENE
+receptors	I-GENE
+that	O
+result	O
+in	O
+the	O
+formation	O
+of	O
+effective	O
+dominant	O
+negative	O
+proteins	O
+.	O
+
+Increase	O
+in	O
+blood	O
+NEFA	O
+was	O
+further	O
+augmented	O
+by	O
+fat	O
+plus	O
+AA	O
+supplementation	O
+,	O
+but	O
+no	O
+changes	O
+in	O
+concentrations	O
+of	O
+Lys	O
+or	O
+Met	O
+in	O
+blood	O
+were	O
+found	O
+.	O
+
+Virol	O
+.	O
+
+Comparison	O
+of	O
+the	O
+deduced	O
+amino	B-GENE
+acid	I-GENE
+sequence	I-GENE
+of	I-GENE
+gamma	I-GENE
+-	I-GENE
+kafirin	I-GENE
+with	O
+the	O
+published	O
+sequences	B-GENE
+of	I-GENE
+gamma	I-GENE
+-	I-GENE
+prolamins	I-GENE
+of	I-GENE
+maize	I-GENE
+,	I-GENE
+and	I-GENE
+Coix	I-GENE
+revealed	O
+highly	O
+conserved	O
+domains	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+HAC1	B-GENE
+may	O
+also	O
+be	O
+one	O
+of	O
+the	O
+meiotic	O
+genes	O
+.	O
+
+We	O
+characterized	O
+three	O
+Arabidopsis	O
+thaliana	O
+cDNA	O
+clones	O
+that	O
+could	O
+rescue	O
+the	O
+sterile	O
+phenotype	O
+of	O
+the	O
+Schizosaccharomyces	B-GENE
+pombe	I-GENE
+pde1	I-GENE
+mutant	I-GENE
+,	O
+which	O
+is	O
+defective	O
+in	O
+cAMP	B-GENE
+phosphodiesterase	I-GENE
+.	O
+
+Furthermore	O
+,	O
+the	O
+identification	O
+of	O
+a	O
+Dr1	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+in	O
+A	O
+.	O
+thaliana	O
+strongly	O
+argues	O
+for	O
+the	O
+ubiquity	O
+of	O
+this	O
+protein	O
+among	O
+eukaryotic	O
+genera	O
+and	O
+for	O
+a	O
+conserved	O
+mechanism	O
+to	O
+regulate	O
+transcription	O
+initiation	O
+that	O
+involves	O
+Dr1	B-GENE
+.	O
+
+Similarly	O
+approximately	O
+300	O
+bp	O
+of	O
+sequence	O
+downstream	O
+of	O
+the	O
+translation	O
+terminator	O
+TGA	O
+of	O
+the	O
+beta	B-GENE
+-	I-GENE
+tubulin	I-GENE
+2	I-GENE
+(	O
+BTU2	B-GENE
+)	O
+gene	O
+could	O
+substitute	O
+for	O
+the	O
+3	O
+'	O
+region	O
+of	O
+the	O
+H4	B-GENE
+-	I-GENE
+I	I-GENE
+gene	I-GENE
+.	O
+
+These	O
+data	O
+demonstrate	O
+that	O
+the	O
+STR	B-GENE
+family	I-GENE
+of	O
+genes	O
+is	O
+represented	O
+in	O
+a	O
+nematode	O
+whose	O
+ancestor	O
+appeared	O
+well	O
+before	O
+the	O
+branching	O
+that	O
+gave	O
+rise	O
+to	O
+the	O
+Arthropoda	O
+and	O
+Chordata	O
+.	O
+
+The	O
+pre	O
+-	O
+and	O
+postoperative	O
+haemoglobin	B-GENE
+concentrations	O
+in	O
+the	O
+autologous	O
+group	O
+were	O
+lower	O
+by	O
+15	O
+and	O
+10	O
+g	O
+/	O
+L	O
+,	O
+respectively	O
+,	O
+after	O
+primary	O
+THR	O
+and	O
+by	O
+10	O
+g	O
+/	O
+L	O
+in	O
+both	O
+instances	O
+after	O
+revision	O
+THR	O
+.	O
+
+The	O
+introduction	O
+of	O
+an	O
+acidic	O
+residue	O
+at	O
+the	O
+second	O
+site	O
+was	O
+essential	O
+for	O
+suppression	O
+of	O
+the	O
+Asn	O
+-	O
+285	O
+mutation	O
+because	O
+Lys	O
+-	O
+220	O
+and	O
+Gln	O
+-	O
+220	O
+second	O
+-	O
+site	O
+mutants	O
+of	O
+the	O
+Asn	O
+-	O
+285	O
+mutant	O
+showed	O
+very	O
+low	O
+tetracycline	O
+resistance	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+,	O
+the	O
+cytokine	O
+that	O
+participates	O
+in	O
+the	O
+autocrine	O
+growth	O
+control	O
+of	O
+hairy	O
+cell	O
+leukemia	O
+has	O
+strong	O
+bone	O
+resorptive	O
+properties	O
+.	O
+
+(	O
+iv	O
+)	O
+Although	O
+UCRBP	B-GENE
+has	O
+been	O
+previously	O
+shown	O
+to	O
+act	O
+as	O
+a	O
+transcriptional	O
+repressor	O
+,	O
+we	O
+show	O
+here	O
+that	O
+UCRBP	B-GENE
+can	O
+also	O
+act	O
+as	O
+a	O
+positive	O
+transactivator	O
+of	O
+a	O
+reporter	O
+driven	O
+by	O
+UCR	O
+elements	O
+when	O
+used	O
+in	O
+co	O
+-	O
+transfection	O
+assays	O
+.	O
+
+The	O
+sequence	O
+of	O
+monkey	B-GENE
+opsin	I-GENE
+closely	O
+resembles	O
+the	O
+human	O
+sequence	O
+at	O
+the	O
+nucleotide	O
+and	O
+the	O
+amino	O
+acid	O
+levels	O
+,	O
+with	O
+the	O
+latter	O
+having	O
+only	O
+7	O
+differences	O
+out	O
+of	O
+348	O
+residues	O
+.	O
+
+One	O
+complex	O
+appears	O
+to	O
+be	O
+ubiquitous	O
+but	O
+enriched	O
+in	O
+lymphoid	O
+cells	O
+and	O
+represents	O
+the	O
+binding	O
+of	O
+a	O
+potentially	O
+novel	O
+factor	O
+with	O
+an	O
+apparent	O
+molecular	O
+mass	O
+of	O
+approximately	O
+50	O
+kDa	O
+.	O
+
+Chem	O
+.	O
+
+Conversely	O
+,	O
+activation	O
+of	O
+Oct	B-GENE
+-	I-GENE
+3	I-GENE
+/	I-GENE
+4	I-GENE
+promoter	I-GENE
+by	O
+RAR	B-GENE
+:	O
+RXR	B-GENE
+heterodimers	I-GENE
+was	O
+completely	O
+abolished	O
+by	O
+EAR	B-GENE
+-	I-GENE
+3	I-GENE
+/	O
+COUP	B-GENE
+-	I-GENE
+TFI	I-GENE
+and	O
+by	O
+ARP	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+COUP	B-GENE
+-	I-GENE
+TFII	I-GENE
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+EKLF	B-GENE
+provides	O
+a	O
+crucial	O
+transactivation	O
+function	O
+for	O
+globin	B-GENE
+expression	O
+and	O
+further	O
+reinforce	O
+the	O
+idea	O
+that	O
+EKLF	B-GENE
+is	O
+an	O
+important	O
+regulator	O
+of	O
+CACCC	O
+element	O
+-	O
+directed	O
+transcription	O
+in	O
+erythroid	O
+cells	O
+.	O
+
+Using	O
+a	O
+battery	O
+of	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+mutants	I-GENE
+,	O
+we	O
+show	O
+that	O
+(	O
+i	O
+)	O
+a	O
+dimer	O
+binds	O
+a	O
+single	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+molecule	I-GENE
+,	O
+(	O
+ii	O
+)	O
+the	O
+acidic	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+is	O
+not	O
+required	O
+for	O
+protein	O
+-	O
+protein	O
+binding	O
+and	O
+does	O
+not	O
+mask	O
+the	O
+nuclear	O
+localization	O
+signal	O
+of	O
+the	O
+dimer	O
+,	O
+(	O
+iii	O
+)	O
+the	O
+same	O
+C	O
+-	O
+terminal	O
+region	O
+is	O
+required	O
+for	O
+inhibition	O
+of	O
+DNA	O
+binding	O
+,	O
+and	O
+(	O
+iv	O
+)	O
+this	O
+inhibition	O
+may	O
+be	O
+accomplished	O
+by	O
+direct	O
+interaction	O
+between	O
+the	O
+PEST	O
+-	O
+like	O
+region	O
+and	O
+the	O
+DNA	O
+-	O
+binding	O
+region	O
+of	O
+one	O
+of	O
+the	O
+subunits	O
+of	O
+the	O
+dimer	O
+.	O
+
+The	O
+negative	O
+regulatory	O
+activity	O
+of	O
+the	O
+N	O
+-	O
+terminal	O
+domain	O
+was	O
+antagonized	O
+by	O
+a	O
+C	O
+-	O
+terminal	O
+segment	O
+of	O
+Pho81p	B-GENE
+supplied	O
+in	O
+trans	O
+.	O
+
+At	O
+different	O
+times	O
+of	O
+the	O
+surgical	O
+procedures	O
+(	O
+thorax	O
+opening	O
+and	O
+closure	O
+,	O
+period	O
+of	O
+cardiopulmonary	O
+bypass	O
+)	O
+67	O
+to	O
+100	O
+%	O
+of	O
+the	O
+patients	O
+in	O
+group	O
+1	O
+had	O
+vancomycin	O
+concentrations	O
+in	O
+the	O
+studied	O
+tissues	O
+above	O
+the	O
+MIC	O
+90	O
+for	O
+Staphylococcus	O
+aureus	O
+(	O
+1	O
+microgram	O
+/	O
+g	O
+)	O
+and	O
+Staphylococcus	O
+epidermidis	O
+(	O
+2	O
+micrograms	O
+/	O
+g	O
+)	O
+.	O
+
+On	O
+-	O
+line	O
+angioscopic	O
+images	O
+of	O
+tissue	O
+flaps	O
+floating	O
+in	O
+the	O
+lumen	O
+,	O
+recent	O
+or	O
+structured	O
+thrombi	O
+,	O
+artery	O
+wall	O
+dissections	O
+,	O
+plaque	O
+ruptures	O
+,	O
+deep	O
+fissurations	O
+and	O
+sub	O
+-	O
+intimal	O
+haemorrhages	O
+demonstrate	O
+,	O
+in	O
+live	O
+colour	O
+,	O
+the	O
+pathophysiological	O
+mechanisms	O
+of	O
+coronary	O
+artery	O
+stenosis	O
+.	O
+
+The	O
+enhanced	O
+cysteine	O
+formation	O
+in	O
+a	O
+pCSK4F	O
+plant	O
+responding	O
+to	O
+sulfite	O
+was	O
+also	O
+observed	O
+in	O
+leaf	O
+discs	O
+.	O
+
+Each	O
+type	O
+was	O
+divided	O
+into	O
+two	O
+subgroups	O
+on	O
+the	O
+basis	O
+of	O
+whether	O
+the	O
+body	O
+and	O
+tail	O
+of	O
+the	O
+pancreas	O
+showed	O
+intense	O
+fatty	O
+replacement	O
+(	O
+type	O
+a	O
+=	O
+negative	O
+for	O
+intense	O
+fatty	O
+replacement	O
+,	O
+type	O
+b	O
+=	O
+positive	O
+for	O
+intense	O
+fatty	O
+replacement	O
+)	O
+.	O
+
+A	O
+new	O
+hypothesis	O
+on	O
+mechanisms	O
+for	O
+inhibiting	O
+catalytic	O
+subunits	O
+by	O
+gamma	O
+-	O
+subunits	O
+and	O
+activation	O
+of	O
+a	O
+holoenzyme	O
+by	O
+transducin	B-GENE
+
+Binding	O
+of	O
+SSP	B-GENE
+to	O
+the	O
+stage	B-GENE
+selector	I-GENE
+element	I-GENE
+(	O
+SSE	B-GENE
+)	O
+in	O
+the	O
+proximal	O
+gamma	B-GENE
+-	I-GENE
+globin	I-GENE
+promoter	I-GENE
+is	O
+integral	O
+to	O
+the	O
+competitive	O
+silencing	O
+of	O
+a	O
+linked	O
+beta	B-GENE
+-	I-GENE
+promoter	I-GENE
+in	O
+embryonic	O
+/	O
+fetal	O
+stage	O
+erythroleukemia	O
+(	O
+K562	O
+)	O
+cells	O
+.	O
+
+This	O
+failure	O
+to	O
+execute	O
+regulated	O
+G1	O
+/	O
+S	O
+arrest	O
+is	O
+correlated	O
+with	O
+enhanced	O
+thermosensitivity	O
+of	O
+colony	O
+-	O
+forming	O
+ability	O
+.	O
+
+Mutations	O
+that	O
+alter	O
+photoreceptor	O
+cell	O
+structure	O
+and	O
+development	O
+were	O
+isolated	O
+that	O
+fail	O
+to	O
+complement	O
+these	O
+deletions	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+the	O
+telomeres	O
+of	O
+the	O
+two	O
+nuclei	O
+have	O
+different	O
+functions	O
+.	O
+
+The	O
+marker	O
+orders	O
+from	O
+the	O
+genetic	O
+and	O
+RH	O
+maps	O
+were	O
+consistent	O
+.	O
+
+Integrated	O
+mapping	O
+analysis	O
+of	O
+the	O
+Werner	O
+syndrome	O
+region	O
+of	O
+chromosome	O
+8	O
+.	O
+
+The	O
+region	O
+between	O
+DXS52	B-GENE
+and	O
+Factor	B-GENE
+VIII	I-GENE
+gene	I-GENE
+in	O
+the	O
+human	O
+Xq28	O
+chromosomal	O
+band	O
+contains	O
+a	O
+G	O
++	O
+C	O
+-	O
+rich	O
+isochore	O
+to	O
+which	O
+many	O
+genes	O
+have	O
+been	O
+mapped	O
+.	O
+
+Haplotype	O
+mapping	O
+and	O
+sequence	O
+analysis	O
+of	O
+the	O
+mouse	O
+Nramp	B-GENE
+gene	I-GENE
+predict	O
+susceptibility	O
+to	O
+infection	O
+with	O
+intracellular	O
+parasites	O
+.	O
+
+This	O
+utilization	O
+of	O
+an	O
+intronic	O
+polyadenylation	O
+site	O
+without	O
+alternative	O
+exon	O
+usage	O
+is	O
+comparable	O
+to	O
+the	O
+mechanism	O
+whereby	O
+both	O
+secreted	O
+and	O
+membrane	O
+-	O
+bound	O
+forms	O
+of	O
+the	O
+immunoglobulin	B-GENE
+mu	I-GENE
+heavy	I-GENE
+chain	I-GENE
+are	O
+made	O
+from	O
+a	O
+single	O
+genetic	O
+locus	O
+.	O
+
+To	O
+further	O
+our	O
+knowledge	O
+about	O
+the	O
+systemic	O
+humoral	O
+immune	O
+system	O
+response	O
+to	O
+weak	O
+hapten	O
+-	O
+syngeneic	O
+or	O
+allogeneic	O
+protein	O
+conjugates	O
+(	O
+corrosion	O
+and	O
+wear	O
+products	O
+of	O
+metallic	O
+orthopedic	O
+devices	O
+)	O
+,	O
+a	O
+sensitive	O
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+(	O
+ELISA	O
+)	O
+method	O
+for	O
+testing	O
+for	O
+antibody	O
+(	O
+humoral	O
+immunity	O
+)	O
+to	O
+metals	O
+was	O
+developed	O
+.	O
+
+In	O
+contrast	O
+,	O
+peak	O
+filling	O
+rate	O
+(	O
+PFR	O
+)	O
+,	O
+normalized	O
+to	O
+end	O
+diastolic	O
+volume	O
+(	O
+EDV	O
+)	O
+,	O
+or	O
+stroke	O
+volume	O
+(	O
+SV	O
+)	O
+,	O
+or	O
+expressed	O
+as	O
+the	O
+ratio	O
+of	O
+PFR	O
+-	O
+to	O
+-	O
+PER	O
+was	O
+reduced	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+time	O
+to	O
+PFR	O
+(	O
+TPFR	O
+)	O
+was	O
+prolonged	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+echocardiographic	O
+left	O
+ventricular	O
+mass	O
+index	O
+was	O
+higher	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+patients	O
+with	O
+acromegaly	O
+compared	O
+to	O
+normals	O
+.	O
+
+A	O
+genetic	O
+complementation	O
+system	O
+was	O
+developed	O
+in	O
+which	O
+tobacco	B-GENE
+etch	I-GENE
+virus	I-GENE
+(	I-GENE
+TEV	I-GENE
+)	I-GENE
+polymerase	I-GENE
+(	O
+NIb	B-GENE
+)	O
+-	O
+expressing	O
+transgenic	O
+plants	O
+or	O
+protoplasts	O
+were	O
+inoculated	O
+with	O
+NIb	B-GENE
+-	O
+defective	O
+TEV	B-GENE
+mutants	I-GENE
+.	O
+
+Nucleotide	O
+sequence	O
+and	O
+transcriptional	O
+analysis	O
+of	O
+the	O
+DNA	B-GENE
+polymerase	I-GENE
+gene	I-GENE
+of	I-GENE
+Bombyx	I-GENE
+mori	I-GENE
+nuclear	I-GENE
+polyhedrosis	I-GENE
+virus	I-GENE
+.	O
+
+Comparison	O
+of	O
+the	O
+genomes	O
+of	O
+PMTV	O
+,	O
+BNYVV	O
+,	O
+and	O
+SBWMV	O
+shows	O
+that	O
+furoviruses	O
+exhibit	O
+considerable	O
+heterogeneity	O
+in	O
+genome	O
+organization	O
+.	O
+
+The	O
+drug	O
+sensitivity	O
+was	O
+100	O
+%	O
+for	O
+vancomycin	O
+(	O
+VCM	O
+)	O
+,	O
+30	O
+%	O
+for	O
+imipenam	O
+(	O
+IMP	O
+)	O
+,	O
+31	O
+%	O
+for	O
+minomycin	O
+(	O
+MINO	O
+)	O
+,	O
+31	O
+%	O
+for	O
+amikacin	O
+(	O
+AMK	O
+)	O
+,	O
+and	O
+7	O
+%	O
+for	O
+fosfomycin	O
+(	O
+FOM	O
+)	O
+.	O
+
+Deglycosylation	O
+with	O
+endoglycosidase	B-GENE
+H	I-GENE
+showed	O
+that	O
+the	O
+mutant	O
+receptors	O
+had	O
+mainly	O
+high	O
+-	O
+mannose	O
+oligosaccharide	O
+chains	O
+.	O
+
+Dietary	O
+supplement	O
+with	O
+fish	O
+oil	O
+and	O
+related	O
+n	O
+-	O
+3	O
+EFAs	O
+has	O
+been	O
+used	O
+to	O
+study	O
+their	O
+antihypertensive	O
+property	O
+in	O
+animals	O
+and	O
+humans	O
+with	O
+borderline	O
+and	O
+essential	O
+hypertension	O
+.	O
+
+The	O
+HSD3B1	B-GENE
+and	O
+HSD3B2	B-GENE
+genes	I-GENE
+encoding	O
+the	O
+types	B-GENE
+I	I-GENE
+and	I-GENE
+II	I-GENE
+3	I-GENE
+beta	I-GENE
+-	I-GENE
+HSD	I-GENE
+isoenzymes	I-GENE
+,	O
+respectively	O
+,	O
+have	O
+been	O
+previously	O
+assigned	O
+by	O
+in	O
+situ	O
+hybridization	O
+to	O
+the	O
+chromosome	O
+1p13	O
+.	O
+1	O
+region	O
+.	O
+
+Therefore	O
+the	O
+prevalences	O
+of	O
+total	O
+diabetes	O
+and	O
+GDM	O
+were	O
+1	O
+.	O
+19	O
+%	O
+and	O
+0	O
+.	O
+56	O
+%	O
+,	O
+respectively	O
+.	O
+
+Insulin	B-GENE
+-	O
+stimulated	O
+glucose	O
+transport	O
+in	O
+adipocytes	O
+is	O
+mediated	O
+by	O
+the	O
+insulin	B-GENE
+receptor	I-GENE
+.	O
+
+After	O
+selection	O
+and	O
+conversion	O
+to	O
+adipocytes	O
+,	O
+the	O
+level	O
+of	O
+EGFR	B-GENE
+expression	O
+was	O
+retained	O
+in	O
+infectant	O
+adipocytes	O
+(	O
+150	O
+,	O
+000	O
+and	O
+250	O
+,	O
+000	O
+/	O
+cell	O
+,	O
+respectively	O
+)	O
+,	O
+but	O
+not	O
+in	O
+the	O
+parental	O
+3T3	O
+-	O
+L1	O
+adipocytes	O
+(	O
+<	O
+5000	O
+/	O
+cell	O
+)	O
+.	O
+
+Intron	O
+-	O
+exon	O
+structure	O
+of	O
+the	O
+porcine	B-GENE
+I	I-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+-	I-GENE
+encoding	I-GENE
+gene	I-GENE
+.	O
+
+Fraction	O
+2	O
+contains	O
+1	O
+,	O
+25	O
+(	O
+OH	O
+)	O
+2	O
+-	O
+vitamin	O
+D3	O
+,	O
+vitamin	O
+D3	O
+,	O
+25	O
+(	O
+OH	O
+)	O
+-	O
+vitamin	O
+D3	O
+and	O
+1	O
+,	O
+24	O
+,	O
+25	O
+(	O
+OH	O
+)	O
+3	O
+-	O
+vitamin	O
+D3	O
+.	O
+
+The	O
+kallistatin	B-GENE
+gene	I-GENE
+was	O
+localized	O
+by	O
+in	O
+situ	O
+hybridization	O
+to	O
+human	O
+chromosome	O
+14q31	O
+-	O
+q32	O
+.	O
+1	O
+,	O
+close	O
+to	O
+the	O
+serpin	B-GENE
+genes	I-GENE
+encoding	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+antichymotrypsin	I-GENE
+,	O
+protein	B-GENE
+C	I-GENE
+inhibitor	I-GENE
+,	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+antitrypsin	I-GENE
+,	O
+and	O
+corticosteroid	B-GENE
+-	I-GENE
+binding	I-GENE
+globulin	I-GENE
+.	O
+
+The	O
+locus	O
+encoding	O
+the	O
+XD	B-GENE
+gene	I-GENE
+(	O
+designated	O
+Xd	B-GENE
+)	O
+was	O
+mapped	O
+to	O
+the	O
+distal	O
+part	O
+of	O
+mouse	O
+chromosome	O
+17	O
+by	O
+haplotype	O
+analysis	O
+of	O
+114	O
+interspecific	O
+backcross	O
+mice	O
+.	O
+
+Some	O
+studies	O
+of	O
+exercise	O
+have	O
+associated	O
+beta	B-GENE
+-	I-GENE
+endorphin	I-GENE
+release	O
+with	O
+increased	O
+exertion	O
+levels	O
+,	O
+but	O
+other	O
+evidence	O
+suggests	O
+that	O
+acidosis	O
+may	O
+stimulate	O
+the	O
+release	O
+of	O
+beta	B-GENE
+-	I-GENE
+endorphin	I-GENE
+.	O
+
+An	O
+interatrial	O
+communication	O
+mitigates	O
+the	O
+impairment	O
+of	O
+LV	O
+function	O
+after	O
+an	O
+acute	O
+and	O
+sustained	O
+drop	O
+of	O
+intrathoracic	O
+pressure	O
+.	O
+
+The	O
+characteristics	O
+of	O
+the	O
+VirD1	B-GENE
+/	O
+VirD2	B-GENE
+-	O
+mediated	O
+cleavage	O
+reaction	O
+strongly	O
+resemble	O
+those	O
+observed	O
+with	O
+relaxosomes	O
+of	O
+IncP	O
+plasmids	O
+involved	O
+in	O
+initiation	O
+of	O
+transfer	O
+DNA	O
+replication	O
+during	O
+bacterial	O
+conjugation	O
+.	O
+
+Isoelectric	O
+focusing	O
+of	O
+tryptic	O
+peptides	O
+generated	O
+from	O
+MHC	B-GENE
+-	I-GENE
+B	I-GENE
+phosphorylated	O
+with	O
+cdc2	B-GENE
+kinase	I-GENE
+revealed	O
+one	O
+major	O
+phosphopeptide	O
+that	O
+was	O
+purified	O
+by	O
+reverse	O
+-	O
+phase	O
+high	O
+performance	O
+liquid	O
+chromatography	O
+and	O
+sequenced	O
+.	O
+
+The	O
+deduced	O
+protein	O
+sequence	O
+was	O
+88	O
+%	O
+homologous	O
+to	O
+that	O
+of	O
+hNUC	B-GENE
+I	I-GENE
+,	O
+isolated	O
+from	O
+human	O
+osteosarcoma	O
+cells	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+Flavobacterium	O
+glycosylasparaginase	B-GENE
+with	O
+a	O
+mammalian	O
+glycosylasparaginase	B-GENE
+revealed	O
+30	O
+%	O
+structural	O
+identity	O
+and	O
+60	O
+%	O
+overall	O
+similarity	O
+between	O
+the	O
+prokaryotic	O
+and	O
+eukaryotic	O
+forms	O
+of	O
+the	O
+enzyme	O
+.	O
+
+Dissociation	O
+and	O
+complexation	O
+of	O
+the	O
+fluoroquinolone	O
+antimicrobials	O
+-	O
+-	O
+an	O
+update	O
+.	O
+
+Superoxide	B-GENE
+dismutase	I-GENE
+(	O
+SOD	B-GENE
+)	O
+activity	O
+decreased	O
+significantly	O
+in	O
+sperm	O
+subjected	O
+to	O
+direct	O
+electric	O
+current	O
+in	O
+comparison	O
+to	O
+the	O
+control	O
+or	O
+the	O
+sample	O
+incubated	O
+with	O
+electrolyzed	O
+medium	O
+.	O
+
+These	O
+studies	O
+indicate	O
+that	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+electrical	O
+stimulation	O
+generate	O
+reactive	O
+oxygen	O
+species	O
+and	O
+affect	O
+SOD	B-GENE
+activity	O
+,	O
+which	O
+in	O
+part	O
+are	O
+responsible	O
+for	O
+decreased	O
+sperm	O
+motion	O
+and	O
+viability	O
+.	O
+
+Sex	O
+selection	O
+via	O
+albumin	B-GENE
+columns	O
+:	O
+20	O
+years	O
+of	O
+results	O
+.	O
+
+They	O
+also	O
+reported	O
+that	O
+E	B-GENE
+mu	I-GENE
+pim	I-GENE
+-	I-GENE
+1	I-GENE
+transgenic	O
+mice	O
+show	O
+greatly	O
+accelerated	O
+lymphoma	O
+development	O
+when	O
+infected	O
+with	O
+wild	O
+-	O
+type	O
+M	O
+-	O
+MuLV	O
+at	O
+birth	O
+.	O
+
+Comparison	O
+of	O
+human	B-GENE
+and	I-GENE
+murine	I-GENE
+blk	I-GENE
+sequences	I-GENE
+indicated	O
+that	O
+they	O
+share	O
+86	O
+%	O
+amino	O
+acid	O
+identity	O
+,	O
+the	O
+most	O
+conserved	O
+region	O
+being	O
+the	O
+catalytic	O
+domain	O
+(	O
+93	O
+%	O
+identity	O
+)	O
+.	O
+
+The	O
+effect	O
+of	O
+ethanol	O
+on	O
+human	O
+sensorimotor	O
+reactivity	O
+was	O
+assessed	O
+by	O
+examining	O
+the	O
+acoustic	O
+startle	O
+response	O
+.	O
+
+Digitalis	O
+glycosides	O
+or	O
+beta	B-GENE
+-	I-GENE
+receptor	I-GENE
+antagonists	O
+are	O
+not	O
+helpful	O
+in	O
+the	O
+therapy	O
+of	O
+this	O
+form	O
+of	O
+atrial	O
+fibrillation	O
+whereas	O
+class	O
+I	O
+antiarrhythmic	O
+drugs	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+more	O
+effective	O
+.	O
+
+Atrial	O
+fibrillation	O
+and	O
+the	O
+autonomic	O
+nervous	O
+system	O
+
+VIII	O
+in	O
+doses	O
+2	O
+-	O
+3	O
+times	O
+higher	O
+than	O
+usually	O
+used	O
+in	O
+haemophiliacs	O
+without	O
+inhibitor	O
+were	O
+successful	O
+.	O
+
+A	O
+reduction	O
+of	O
+the	O
+aspartate	B-GENE
+aminotransferase	I-GENE
+activity	O
+was	O
+observed	O
+from	O
+800	O
+mg	O
+/	O
+kg	O
+b	O
+.	O
+w	O
+.	O
+/	O
+d	O
+onwards	O
+.	O
+
+Thus	O
+,	O
+these	O
+studies	O
+indicate	O
+that	O
+the	O
+104	O
+-	O
+kDa	O
+isoform	O
+is	O
+required	O
+for	O
+normal	O
+proliferation	O
+of	O
+female	O
+germline	O
+cells	O
+and	O
+perhaps	O
+for	O
+oocyte	O
+differentiation	O
+.	O
+
+Physical	O
+analysis	O
+maps	O
+SAL6	B-GENE
+to	O
+chromosome	O
+XVI	O
+between	O
+TPK2	B-GENE
+and	O
+spt14	B-GENE
+.	O
+
+The	O
+newly	O
+devised	O
+DCT	O
+method	O
+yields	O
+reliable	O
+data	O
+in	O
+measuring	O
+TBF	O
+.	O
+
+Removal	O
+of	O
+PDMP	O
+from	O
+the	O
+cell	O
+medium	O
+resulted	O
+in	O
+reversal	O
+of	O
+the	O
+cell	O
+cycle	O
+changes	O
+,	O
+with	O
+cells	O
+re	O
+-	O
+entering	O
+the	O
+S	O
+phase	O
+.	O
+
+Rho	B-GENE
+GDP	I-GENE
+/	I-GENE
+GTP	I-GENE
+exchange	I-GENE
+inhibitor	I-GENE
+,	O
+Rho	B-GENE
+GDI	I-GENE
+,	O
+comigrated	O
+with	O
+Rac2	B-GENE
+and	O
+RhoA	B-GENE
+,	O
+but	O
+not	O
+Rac1	B-GENE
+.	O
+
+Schnell	O
+,	O
+J	O
+.	O
+
+Encapsidation	O
+of	O
+poliovirus	O
+replicons	O
+encoding	O
+the	O
+complete	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+gag	I-GENE
+gene	I-GENE
+by	O
+using	O
+a	O
+complementation	O
+system	O
+which	O
+provides	O
+the	O
+P1	B-GENE
+capsid	I-GENE
+protein	I-GENE
+in	O
+trans	O
+.	O
+
+The	O
+requirement	O
+of	O
+PilE	B-GENE
+in	O
+pilus	O
+biogenesis	O
+was	O
+confirmed	O
+by	O
+demonstrating	O
+that	O
+chromosomal	B-GENE
+pilE	I-GENE
+insertion	I-GENE
+mutants	I-GENE
+were	O
+pilus	O
+-	O
+and	O
+twitching	O
+-	O
+motility	O
+deficient	O
+.	O
+
+The	O
+pilE	B-GENE
+gene	I-GENE
+product	I-GENE
+of	I-GENE
+Pseudomonas	I-GENE
+aeruginosa	I-GENE
+,	O
+required	O
+for	O
+pilus	O
+biogenesis	O
+,	O
+shares	O
+amino	O
+acid	O
+sequence	O
+identity	O
+with	O
+the	O
+N	O
+-	O
+termini	O
+of	O
+type	B-GENE
+4	I-GENE
+prepilin	I-GENE
+proteins	I-GENE
+.	O
+
+Because	O
+of	O
+the	O
+functional	O
+conservation	O
+of	O
+cell	O
+cycle	O
+control	O
+elements	O
+,	O
+the	O
+expression	O
+of	O
+a	O
+vertebrate	B-GENE
+wee1	I-GENE
+or	O
+mik1	B-GENE
+homolog	I-GENE
+would	O
+be	O
+expected	O
+to	O
+rescue	O
+such	O
+lethal	O
+mutations	O
+in	O
+yeast	O
+.	O
+
+The	O
+expression	O
+of	O
+this	O
+clone	O
+in	O
+a	O
+wee1	B-GENE
+/	O
+mik1	B-GENE
+-	O
+deficient	O
+mutant	O
+causes	O
+an	O
+elongated	O
+cell	O
+phenotype	O
+under	O
+non	O
+-	O
+permissive	O
+growth	O
+conditions	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+phosphorylation	O
+of	O
+M	B-GENE
+protein	I-GENE
+at	O
+the	O
+major	O
+in	O
+vivo	O
+sites	O
+is	O
+not	O
+essential	O
+for	O
+virus	O
+assembly	O
+.	O
+
+Near	O
+a	O
+third	O
+(	O
+31	O
+.	O
+6	O
+%	O
+)	O
+of	O
+Insulin	B-GENE
+Dependent	O
+and	O
+a	O
+third	O
+(	O
+33	O
+.	O
+41	O
+%	O
+)	O
+for	O
+Non	O
+Insulin	B-GENE
+Dependent	O
+were	O
+of	O
+D	O
+,	O
+F	O
+,	O
+H	O
+White	O
+'	O
+s	O
+Class	O
+.	O
+
+The	O
+activity	O
+of	O
+6	O
+-	O
+fluoroquinolones	O
+and	O
+their	O
+nonfluorinated	O
+derivatives	O
+is	O
+compared	O
+in	O
+general	O
+.	O
+
+As	O
+the	O
+half	O
+-	O
+life	O
+of	O
+the	O
+compound	O
+did	O
+never	O
+exceed	O
+8	O
+-	O
+9	O
+h	O
+,	O
+the	O
+data	O
+do	O
+not	O
+support	O
+any	O
+change	O
+of	O
+pidotimod	O
+administration	O
+schedule	O
+(	O
+every	O
+24	O
+-	O
+12	O
+h	O
+)	O
+.	O
+
+The	O
+MAP	B-GENE
+kinase	I-GENE
+cascade	O
+is	O
+highly	O
+conserved	O
+in	O
+all	O
+eukaryotes	O
+and	O
+involved	O
+in	O
+numerous	O
+cellular	O
+responses	O
+.	O
+
+A	O
+comparative	O
+study	O
+by	O
+holographic	O
+interferometry	O
+of	O
+ten	O
+porcine	O
+bioprosthetic	O
+valves	O
+(	O
+seven	O
+Carpentier	O
+-	O
+Edwards	O
+SAV	O
+,	O
+two	O
+BioImplant	O
+and	O
+one	O
+Valcor	O
+)	O
+with	O
+five	O
+human	O
+aortic	O
+valves	O
+before	O
+and	O
+after	O
+glutaraldehyde	O
+treatment	O
+is	O
+presented	O
+.	O
+
+No	O
+serious	O
+side	O
+effects	O
+were	O
+observed	O
+.	O
+
+This	O
+region	O
+constitutes	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+with	O
+basic	O
+-	O
+helix	O
+-	O
+loop	O
+-	O
+helix	O
+and	O
+leucine	O
+-	O
+zipper	O
+motifs	O
+,	O
+features	O
+common	O
+to	O
+the	O
+myc	B-GENE
+-	I-GENE
+related	I-GENE
+transcription	I-GENE
+factor	I-GENE
+family	I-GENE
+.	O
+
+The	O
+mean	O
+jitter	O
+and	O
+the	O
+fiber	O
+density	O
+did	O
+not	O
+change	O
+significantly	O
+from	O
+day	O
+0	O
+(	O
+30	O
+.	O
+1	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+microseconds	O
+;	O
+1	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+07	O
+)	O
+to	O
+day	O
+30	O
+(	O
+34	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+.	O
+7	O
+microseconds	O
+;	O
+1	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+)	O
+.	O
+
+Lack	O
+of	O
+cyclin	B-GENE
+D	I-GENE
+-	O
+Cdk	B-GENE
+complexes	O
+in	O
+Rb	B-GENE
+-	O
+negative	O
+cells	O
+correlates	O
+with	O
+high	O
+levels	O
+of	O
+p16INK4	B-GENE
+/	O
+MTS1	B-GENE
+tumour	O
+suppressor	O
+gene	O
+product	O
+.	O
+
+Recombinant	B-GENE
+human	I-GENE
+serum	I-GENE
+albumin	I-GENE
+(	O
+rHSA	B-GENE
+)	O
+produced	O
+by	O
+cultured	O
+fermentation	O
+has	O
+been	O
+prepared	O
+in	O
+the	O
+form	O
+of	O
+microcapsules	O
+nominally	O
+3	O
+-	O
+5	O
+microns	O
+in	O
+diameter	O
+and	O
+radiolabelled	O
+with	O
+technetium	O
+-	O
+99m	O
+following	O
+reduction	O
+with	O
+stannous	O
+chloride	O
+.	O
+
+We	O
+have	O
+measured	O
+the	O
+release	O
+of	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+tumour	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+)	O
+by	O
+unstimulated	O
+monocytes	O
+and	O
+monocytes	O
+stimulated	O
+with	O
+lipopolysaccharide	O
+(	O
+LPS	O
+)	O
+isolated	O
+from	O
+the	O
+peripheral	O
+blood	O
+of	O
+two	O
+patients	O
+with	O
+acute	O
+poststreptococcal	O
+glomerulonephritis	O
+(	O
+AGN	O
+)	O
+and	O
+16	O
+healthy	O
+controls	O
+.	O
+
+Such	O
+an	O
+intervention	O
+may	O
+be	O
+of	O
+considerable	O
+use	O
+for	O
+the	O
+treatment	O
+of	O
+angiogenesis	O
+-	O
+dependent	O
+diseases	O
+involving	O
+FGF	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+UV	O
+cross	O
+-	O
+linking	O
+experiments	O
+show	O
+that	O
+TEP	B-GENE
+has	O
+an	O
+apparent	O
+molecular	O
+mass	O
+of	O
+approximately	O
+65	O
+kDa	O
+.	O
+
+Alternatively	O
+,	O
+loss	O
+-	O
+of	O
+-	O
+function	O
+alleles	O
+of	O
+genes	O
+that	O
+inhibit	O
+cAPK	B-GENE
+lead	O
+to	O
+the	O
+inability	O
+to	O
+undergo	O
+sexual	O
+differentiation	O
+.	O
+
+One	O
+member	O
+of	O
+this	O
+family	O
+,	O
+RFX1	B-GENE
+,	O
+is	O
+a	O
+transcription	O
+factor	O
+for	O
+a	O
+variety	O
+of	O
+viral	O
+and	O
+cellular	O
+genes	O
+.	O
+
+This	O
+mutant	O
+was	O
+identified	O
+by	O
+screening	O
+with	O
+a	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+-	O
+inducible	O
+vector	O
+a	O
+series	O
+of	O
+mink	O
+lung	O
+epithelial	O
+cell	O
+clones	O
+that	O
+have	O
+normal	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+binding	O
+activity	O
+but	O
+have	O
+lost	O
+antiproliferative	O
+and	O
+transcriptional	O
+responses	O
+to	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+.	O
+
+Cloning	O
+by	O
+complementation	O
+and	O
+subsequent	O
+physical	O
+and	O
+genetic	O
+analysis	O
+revealed	O
+that	O
+it	O
+maps	O
+to	O
+RAF1	B-GENE
+.	O
+
+In	O
+the	O
+presence	O
+of	O
+inositol	O
+and	O
+choline	O
+(	O
+repressing	O
+)	O
+,	O
+the	O
+product	O
+of	O
+the	O
+OPI1	B-GENE
+gene	I-GENE
+represses	O
+transcription	O
+dictated	O
+by	O
+the	O
+UASINO	O
+element	O
+.	O
+
+By	O
+treating	O
+monkey	O
+COS	O
+cells	O
+with	O
+oligonucleotides	O
+linked	O
+to	O
+psoralen	O
+,	O
+we	O
+have	O
+generated	O
+targeted	O
+mutations	O
+in	O
+a	O
+simian	O
+virus	O
+40	O
+(	O
+SV40	O
+)	O
+vector	O
+contained	O
+within	O
+the	O
+cells	O
+via	O
+intracellular	O
+triple	O
+helix	O
+formation	O
+.	O
+
+The	O
+interleukin	B-GENE
+2	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+-	I-GENE
+chain	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+2R	I-GENE
+alpha	I-GENE
+)	O
+gene	O
+is	O
+rapidly	O
+and	O
+potently	O
+induced	O
+in	O
+T	O
+cells	O
+in	O
+response	O
+to	O
+mitogenic	O
+stimuli	O
+.	O
+
+The	O
+Wilms	B-GENE
+'	I-GENE
+tumour	I-GENE
+suppressor	I-GENE
+protein	I-GENE
+(	O
+WT1	B-GENE
+)	O
+is	O
+a	O
+putative	O
+transcriptional	O
+regulatory	O
+protein	O
+with	O
+four	O
+zinc	O
+fingers	O
+,	O
+the	O
+last	O
+three	O
+of	O
+which	O
+have	O
+extensive	O
+sequence	O
+homology	O
+to	O
+the	O
+early	B-GENE
+growth	I-GENE
+response	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+EGR	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+protein	O
+.	O
+
+OBJECTIVES	O
+:	O
+1	O
+)	O
+to	O
+determine	O
+serum	B-GENE
+ACE	I-GENE
+activity	O
+in	O
+patients	O
+with	O
+COPD	O
+treated	O
+with	O
+and	O
+without	O
+continuous	O
+ambulatory	O
+oxygen	O
+therapy	O
+(	O
+CAOT	O
+)	O
+;	O
+2	O
+)	O
+to	O
+verify	O
+whether	O
+there	O
+is	O
+a	O
+correlation	O
+between	O
+ACE	B-GENE
+and	O
+any	O
+hematological	O
+,	O
+spirometric	O
+or	O
+gasometric	O
+parameter	O
+.	O
+
+In	O
+order	O
+to	O
+infer	O
+shape	O
+from	O
+contour	O
+,	O
+the	O
+human	O
+visual	O
+system	O
+must	O
+selectively	O
+integrate	O
+fragments	O
+projecting	O
+from	O
+a	O
+common	O
+object	O
+while	O
+keeping	O
+fragments	O
+from	O
+different	O
+objects	O
+separate	O
+.	O
+
+Among	O
+9	O
+group	O
+I	O
+patients	O
+with	O
+a	O
+positive	O
+result	O
+on	O
+head	O
+-	O
+up	O
+tilt	O
+-	O
+table	O
+testing	O
+and	O
+no	O
+evidence	O
+of	O
+structural	O
+heart	O
+disease	O
+(	O
+mean	O
+follow	O
+-	O
+up	O
+4	O
+.	O
+3	O
+years	O
+)	O
+,	O
+7	O
+are	O
+without	O
+further	O
+episodes	O
+of	O
+syncope	O
+;	O
+3	O
+have	O
+discontinued	O
+medication	O
+and	O
+5	O
+have	O
+resumed	O
+at	O
+least	O
+limited	O
+exercise	O
+.	O
+
+Constructs	O
+designed	O
+and	O
+expressed	O
+were	O
+E2L1	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+98	I-GENE
+)	I-GENE
+,	O
+E2L1	B-GENE
+.	I-GENE
+H1	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+128	I-GENE
+)	I-GENE
+,	O
+E2L2	B-GENE
+(	I-GENE
+120	I-GENE
+-	I-GENE
+233	I-GENE
+)	I-GENE
+,	O
+E2H1	B-GENE
+.	I-GENE
+L2	I-GENE
+(	I-GENE
+98	I-GENE
+-	I-GENE
+233	I-GENE
+)	I-GENE
+,	O
+and	O
+E2L1	B-GENE
+.	I-GENE
+H1	I-GENE
+.	I-GENE
+L2	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+233	I-GENE
+)	I-GENE
+,	O
+where	O
+numbers	O
+in	O
+parentheses	O
+give	O
+the	O
+amino	O
+acid	O
+sequence	O
+for	O
+the	O
+portions	O
+of	O
+the	O
+E2	B-GENE
+component	O
+incorporated	O
+into	O
+a	O
+construct	O
+.	O
+
+Thus	O
+,	O
+we	O
+have	O
+produced	O
+lipoyl	O
+domain	O
+constructs	O
+that	O
+can	O
+be	O
+employed	O
+in	O
+sorting	O
+the	O
+specific	O
+roles	O
+of	O
+E2L1	B-GENE
+and	O
+E2L2	B-GENE
+in	O
+facilitating	O
+catalytic	O
+and	O
+regulatory	O
+processes	O
+.	O
+
+METHODS	O
+:	O
+Ten	O
+influenza	O
+A	O
+(	O
+H3N2	O
+)	O
+viruses	O
+isolated	O
+during	O
+the	O
+outbreaks	O
+were	O
+examined	O
+for	O
+resistance	O
+to	O
+amantadine	O
+and	O
+rimantadine	O
+by	O
+means	O
+of	O
+an	O
+enzyme	O
+immunoassay	O
+and	O
+by	O
+sequencing	O
+of	O
+the	O
+viral	O
+nucleic	O
+acid	O
+that	O
+encodes	O
+the	O
+transmembrane	O
+domain	O
+of	O
+the	O
+M2	B-GENE
+protein	I-GENE
+.	O
+
+The	O
+first	O
+contains	O
+ATF	B-GENE
+/	O
+CRE	O
+and	O
+TBP	B-GENE
+/	O
+TATA	O
+sequence	O
+motifs	O
+within	O
+an	O
+87	O
+-	O
+bp	O
+region	O
+.	O
+
+Gene	O
+expression	O
+occurs	O
+in	O
+a	O
+circadian	O
+rhythm	O
+and	O
+induced	O
+by	O
+light	O
+in	O
+leaves	O
+of	O
+dark	O
+-	O
+adapted	O
+plants	O
+.	O
+
+Our	O
+results	O
+suggested	O
+that	O
+the	O
+hexamer	O
+and	O
+the	O
+octamer	O
+motifs	O
+may	O
+play	O
+important	O
+role	O
+(	O
+s	O
+)	O
+in	O
+regulation	O
+of	O
+replication	O
+-	O
+dependent	O
+but	O
+not	O
+of	O
+replication	O
+-	O
+independent	O
+expression	O
+of	O
+the	O
+wheat	B-GENE
+histone	I-GENE
+H3	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+tissue	O
+-	O
+specific	O
+expression	O
+of	O
+DP	B-GENE
+family	I-GENE
+members	I-GENE
+suggests	O
+that	O
+the	O
+combination	O
+of	O
+DP	B-GENE
+/	O
+E2F	B-GENE
+heterodimers	O
+that	O
+constitute	O
+DRTF1	B-GENE
+/	O
+E2F	B-GENE
+is	O
+influenced	O
+by	O
+the	O
+phenotype	O
+of	O
+the	O
+cell	O
+.	O
+
+In	O
+a	O
+second	O
+experiment	O
+involving	O
+an	O
+18	O
+-	O
+h	O
+lung	O
+clearance	O
+assay	O
+,	O
+we	O
+used	O
+the	O
+mAb	B-GENE
+3	I-GENE
+.	I-GENE
+2	I-GENE
+.	I-GENE
+3	I-GENE
+to	O
+deplete	O
+rats	O
+of	O
+LGL	O
+/	O
+NK	O
+cells	O
+with	O
+the	O
+following	O
+rationale	O
+:	O
+if	O
+LGL	O
+/	O
+NK	O
+cells	O
+are	O
+necessary	O
+to	O
+mediate	O
+an	O
+event	O
+,	O
+then	O
+in	O
+their	O
+absence	O
+,	O
+that	O
+event	O
+should	O
+not	O
+occur	O
+.	O
+
+Treatment	O
+of	O
+recurrent	O
+FSGS	O
+has	O
+included	O
+high	O
+-	O
+dose	O
+steroids	O
+,	O
+high	O
+-	O
+dose	O
+cyclosporine	O
+(	O
+CSA	O
+)	O
+,	O
+plasmapheresis	O
+,	O
+and	O
+ACE	B-GENE
+inhibitors	O
+with	O
+mixed	O
+results	O
+.	O
+
+Our	O
+results	O
+concluded	O
+that	O
+1	O
+)	O
+the	O
+two	O
+inhibin	B-GENE
+/	O
+activin	B-GENE
+beta	O
+B	O
+-	O
+subunit	O
+mRNAs	O
+were	O
+transcribed	O
+from	O
+different	O
+initiation	O
+sites	O
+;	O
+2	O
+)	O
+both	O
+promoters	O
+may	O
+be	O
+controlled	O
+by	O
+up	O
+-	O
+stream	O
+negative	O
+regulatory	O
+elements	O
+;	O
+and	O
+3	O
+)	O
+neither	O
+of	O
+these	O
+promoters	O
+is	O
+responsive	O
+to	O
+cAMP	O
+and	O
+/	O
+or	O
+phorbol	O
+esters	O
+under	O
+the	O
+conditions	O
+employed	O
+.	O
+
+Promoter	O
+region	O
+of	O
+the	O
+transcriptional	O
+unit	O
+for	O
+human	B-GENE
+alpha	I-GENE
+1	I-GENE
+-	I-GENE
+chimaerin	I-GENE
+,	O
+a	O
+neuron	B-GENE
+-	I-GENE
+specific	I-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+for	O
+p21rac	B-GENE
+.	O
+alpha	B-GENE
+1	I-GENE
+-	I-GENE
+chimaerin	I-GENE
+is	O
+a	O
+neuron	B-GENE
+-	I-GENE
+specific	I-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+for	O
+p21rac	B-GENE
+,	O
+a	O
+protein	O
+involved	O
+in	O
+morphological	O
+events	O
+.	O
+
+Upstream	O
+from	O
+the	O
+transcription	O
+start	O
+point	O
+(	O
+tsp	O
+)	O
+,	O
+a	O
+nucleotide	O
+sequence	O
+highly	O
+homologous	O
+to	O
+the	O
+consensus	B-GENE
+sequence	I-GENE
+motif	I-GENE
+for	I-GENE
+the	I-GENE
+sigma	I-GENE
+35	I-GENE
+-	I-GENE
+recognized	I-GENE
+promoters	I-GENE
+was	O
+found	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+an	O
+analysis	O
+of	O
+the	O
+dynamics	O
+in	O
+the	O
+closing	O
+phase	O
+of	O
+the	O
+occluder	O
+of	O
+a	O
+mechanical	O
+monoleaflet	O
+heart	O
+valve	O
+prosthesis	O
+is	O
+presented	O
+.	O
+
+During	O
+ISO	O
++	O
+AT	O
+infusion	O
+,	O
+abdominal	O
+fat	O
+blood	O
+flow	O
+was	O
+still	O
+significantly	O
+increased	O
+as	O
+compared	O
+with	O
+control	O
+values	O
+in	O
+lean	O
+and	O
+obese	O
+subjects	O
+.	O
+
+When	O
+expressed	O
+per	O
+kilogram	O
+body	O
+weight	O
+,	O
+mean	O
+GIT	O
+increased	O
+in	O
+the	O
+dF	O
+group	O
+from	O
+0	O
+.	O
+14	O
+%	O
+to	O
+0	O
+.	O
+16	O
+%	O
+above	O
+RMR	O
+,	O
+with	O
+a	O
+significant	O
+decrease	O
+from	O
+0	O
+.	O
+15	O
+%	O
+to	O
+0	O
+.	O
+13	O
+%	O
+in	O
+the	O
+P	O
+group	O
+.	O
+
+In	O
+nucleus	O
+ventralis	O
+anterior	O
+thalami	O
+-	O
+nucleus	O
+ventralis	O
+lateralis	O
+thalami	O
+neurons	O
+with	O
+an	O
+inhibitory	O
+input	O
+from	O
+nucleus	O
+entopeduncularis	O
+,	O
+a	O
+shortening	O
+of	O
+inhibition	O
+from	O
+17	O
+.	O
+5	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+to	O
+9	O
+.	O
+1	O
++	O
+/	O
+-	O
+1	O
+.	O
+8	O
+ms	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+under	O
+the	O
+haloperidol	O
+influence	O
+was	O
+evident	O
+.	O
+
+However	O
+,	O
+inclusion	O
+of	O
+the	O
+neighboring	O
+CGGAAR	O
+motifs	O
+from	O
+the	O
+ICP4	B-GENE
+promoter	I-GENE
+,	O
+which	O
+bind	O
+factors	O
+GABP	B-GENE
+alpha	I-GENE
+and	I-GENE
+beta	I-GENE
+,	O
+results	O
+in	O
+a	O
+strong	O
+synergistic	O
+activation	O
+.	O
+
+This	O
+finding	O
+represents	O
+both	O
+a	O
+potentially	O
+important	O
+mechanism	O
+by	O
+which	O
+HPV	O
+gene	O
+expression	O
+can	O
+be	O
+regulated	O
+and	O
+an	O
+interesting	O
+model	O
+for	O
+the	O
+study	O
+of	O
+transcriptional	O
+cooperativity	O
+.	O
+
+Using	O
+this	O
+method	O
+,	O
+VLPs	O
+were	O
+obtained	O
+in	O
+quantities	O
+sufficient	O
+for	O
+further	O
+characterization	O
+.	O
+
+Analysis	O
+of	O
+the	O
+sequence	O
+upstream	O
+of	O
+this	O
+initiation	O
+codon	O
+reveals	O
+the	O
+presence	O
+of	O
+a	O
+promotor	O
+sequence	O
+.	O
+
+SUP46	B-GENE
+is	O
+implicated	O
+in	O
+translation	O
+fidelity	O
+and	O
+encodes	O
+the	O
+ribosomal	B-GENE
+protein	I-GENE
+S13	I-GENE
+.	O
+
+To	O
+explore	O
+the	O
+functional	O
+relationship	O
+between	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+and	O
+Rb	B-GENE
+,	O
+a	O
+eukaryotic	O
+expression	O
+plasmid	O
+was	O
+constructed	O
+containing	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+gene	I-GENE
+under	O
+control	O
+of	O
+the	O
+SV40	B-GENE
+promoter	I-GENE
+complex	O
+.	O
+
+The	O
+high	O
+degree	O
+of	O
+sequence	O
+identity	O
+(	O
+96	O
+%	O
+)	O
+between	O
+hydrolase	B-GENE
+B	I-GENE
+and	I-GENE
+C	I-GENE
+,	O
+particularly	O
+in	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+,	O
+suggests	O
+that	O
+the	O
+genes	O
+encoding	O
+these	O
+two	O
+carboxylesterases	B-GENE
+evolved	O
+by	O
+duplication	O
+and	O
+divergence	O
+of	O
+a	O
+common	O
+ancestral	O
+gene	O
+.	O
+
+The	O
+regions	O
+of	O
+the	O
+tooth	O
+fracture	O
+are	O
+determined	O
+.	O
+
+Secondary	O
+pancreatic	O
+involvement	O
+of	O
+mycosis	O
+fungoides	O
+detected	O
+by	O
+a	O
+clinically	O
+palpable	O
+mass	O
+.	O
+
+The	O
+NR2	O
+hybrid	O
+is	O
+a	O
+powerful	O
+tool	O
+for	O
+the	O
+mapping	O
+of	O
+new	O
+probes	O
+of	O
+this	O
+region	O
+,	O
+as	O
+well	O
+as	O
+for	O
+obtaining	O
+new	O
+informative	O
+probes	O
+specific	O
+for	O
+the	O
+deletion	O
+by	O
+subtractive	O
+cloning	O
+of	O
+the	O
+region	O
+.	O
+
+TDEYA	O
+at	O
+doses	O
+of	O
+200	O
+to	O
+500	O
+mg	O
+/	O
+kg	O
+significantly	O
+suppressed	O
+xanthine	B-GENE
+oxidase	I-GENE
+(	O
+XO	B-GENE
+)	O
+activity	O
+in	O
+the	O
+stomach	O
+tissue	O
+following	O
+its	O
+oral	O
+administration	O
+.	O
+
+Like	O
+humans	O
+,	O
+the	O
+PITSLRE	B-GENE
+PK	I-GENE
+genes	I-GENE
+in	I-GENE
+chickens	I-GENE
+must	O
+be	O
+closely	O
+linked	O
+,	O
+based	O
+on	O
+fluorescent	O
+in	O
+situ	O
+hybridization	O
+(	O
+FISH	O
+)	O
+localization	O
+of	O
+these	O
+genes	O
+to	O
+a	O
+single	O
+chicken	O
+microchromosome	O
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+the	O
+characterization	O
+of	O
+an	O
+alternatively	O
+processed	O
+form	O
+of	O
+AFAP	B-GENE
+-	I-GENE
+110	I-GENE
+that	O
+encodes	O
+an	O
+additional	O
+258	O
+base	O
+pair	O
+(	O
+bp	O
+)	O
+of	O
+open	O
+reading	O
+frame	O
+.	O
+
+Expression	O
+of	O
+class	B-GENE
+IV	I-GENE
+ADH	I-GENE
+mRNA	I-GENE
+was	O
+detected	O
+in	O
+human	O
+stomach	O
+but	O
+not	O
+liver	O
+.	O
+
+In	O
+ICE	B-GENE
+gamma	I-GENE
+,	O
+most	O
+of	O
+the	O
+propeptide	O
+(	O
+amino	O
+acids	O
+20	O
+-	O
+112	O
+)	O
+is	O
+deleted	O
+,	O
+which	O
+suggests	O
+that	O
+it	O
+may	O
+function	O
+as	O
+a	O
+catalyst	O
+for	O
+ICE	B-GENE
+autoprocessing	O
+in	O
+vivo	O
+.	O
+
+Endocytosis	O
+and	O
+lysosomal	O
+targeting	O
+of	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptors	I-GENE
+are	O
+mediated	O
+by	O
+distinct	O
+sequences	O
+independent	O
+of	O
+the	O
+tyrosine	B-GENE
+kinase	I-GENE
+domain	I-GENE
+.	O
+
+It	O
+is	O
+now	O
+recognized	O
+that	O
+essentially	O
+all	O
+eukaryotic	O
+and	O
+prokaryotic	O
+genes	O
+whose	O
+5	O
+'	O
+-	O
+flanking	O
+regions	O
+are	O
+known	O
+and	O
+that	O
+encode	O
+barbiturate	O
+-	O
+inducible	O
+proteins	O
+contain	O
+the	O
+Barbie	O
+box	O
+element	O
+.	O
+
+Mutation	O
+of	O
+the	O
+P450BM	B-GENE
+-	I-GENE
+3	I-GENE
+Barbie	I-GENE
+box	I-GENE
+significantly	O
+increased	O
+the	O
+expression	O
+of	O
+both	O
+P450BM	B-GENE
+-	I-GENE
+3	I-GENE
+and	O
+Bm3P1	B-GENE
+(	O
+another	O
+small	O
+gene	O
+located	O
+upstream	O
+of	O
+the	O
+P450BM	B-GENE
+-	I-GENE
+3	I-GENE
+gene	I-GENE
+that	O
+encodes	O
+a	O
+second	O
+putative	O
+regulatory	O
+protein	O
+)	O
+in	O
+response	O
+to	O
+pentobarbital	O
+induction	O
+but	O
+left	O
+the	O
+basal	O
+levels	O
+unaffected	O
+.	O
+
+A	O
+potential	O
+outcome	O
+of	O
+these	O
+biochemical	O
+effects	O
+may	O
+include	O
+the	O
+limited	O
+responsiveness	O
+of	O
+infected	O
+T	O
+cells	O
+to	O
+antigenic	O
+stimulation	O
+observed	O
+during	O
+HIV	O
+-	O
+1	O
+infection	O
+.	O
+
+The	O
+full	O
+protocol	O
+was	O
+completed	O
+by	O
+33	O
+patients	O
+(	O
+45	O
+%	O
+of	O
+original	O
+cohort	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+found	O
+that	O
+cell	O
+-	O
+specific	O
+suppression	O
+of	O
+RA	O
+-	O
+stimulated	O
+zif268	B-GENE
+gene	I-GENE
+expression	O
+can	O
+be	O
+attributed	O
+to	O
+a	O
+29	O
+base	O
+pair	O
+nucleotide	O
+sequence	O
+,	O
+located	O
+downstream	O
+of	O
+the	O
+RA	O
+-	O
+responsive	O
+region	O
+in	O
+the	O
+zif268	B-GENE
+gene	I-GENE
+.	O
+
+We	O
+show	O
+that	O
+CBF	B-GENE
+-	I-GENE
+A	I-GENE
+and	O
+CBF	B-GENE
+-	I-GENE
+C	I-GENE
+interact	O
+with	O
+each	O
+other	O
+to	O
+form	O
+a	O
+CBF	B-GENE
+-	I-GENE
+A	I-GENE
+-	O
+CBF	B-GENE
+-	I-GENE
+C	I-GENE
+complex	O
+and	O
+that	O
+CBF	B-GENE
+-	I-GENE
+B	I-GENE
+does	O
+not	O
+interact	O
+with	O
+CBF	B-GENE
+-	I-GENE
+A	I-GENE
+or	O
+CBF	B-GENE
+-	I-GENE
+C	I-GENE
+individually	O
+but	O
+that	O
+it	O
+associates	O
+with	O
+the	O
+CBF	B-GENE
+-	I-GENE
+A	I-GENE
+-	O
+CBF	B-GENE
+-	I-GENE
+C	I-GENE
+complex	O
+.	O
+
+In	O
+the	O
+first	O
+,	O
+homologous	O
+sequences	O
+were	O
+deleted	O
+from	O
+a	O
+mouse	O
+enhancer	O
+,	O
+resulting	O
+in	O
+a	O
+tissue	O
+-	O
+specific	O
+loss	O
+of	O
+activity	O
+when	O
+assayed	O
+in	O
+transgenic	O
+mice	O
+.	O
+
+OKT3	B-GENE
+prophylaxis	O
+improves	O
+long	O
+-	O
+term	O
+renal	O
+graft	O
+survival	O
+in	O
+high	O
+-	O
+risk	O
+patients	O
+as	O
+compared	O
+to	O
+cyclosporine	O
+:	O
+combined	O
+results	O
+from	O
+the	O
+prospective	O
+,	O
+randomized	O
+Belgian	O
+and	O
+US	O
+studies	O
+.	O
+
+The	O
+major	O
+PKC	B-GENE
+beta	I-GENE
+transcription	O
+initiation	O
+site	O
+was	O
+identified	O
+by	O
+primer	O
+extension	O
+and	O
+S1	B-GENE
+nuclease	I-GENE
+protection	O
+.	O
+
+In	O
+the	O
+course	O
+of	O
+a	O
+study	O
+of	O
+low	O
+dose	O
+X	O
+-	O
+rays	O
+effects	O
+,	O
+we	O
+found	O
+that	O
+male	O
+ICR	O
+white	O
+Swiss	O
+mice	O
+showed	O
+remarkable	O
+suppression	O
+of	O
+mounting	O
+behavior	O
+after	O
+whole	O
+body	O
+irradiation	O
+by	O
+5	O
+to	O
+15	O
+cGy	O
+X	O
+-	O
+rays	O
+.	O
+
+A	O
+quantitative	O
+analysis	O
+of	O
+the	O
+diffraction	O
+intensity	O
+as	O
+function	O
+of	O
+the	O
+accumulated	O
+electron	O
+dose	O
+suggests	O
+the	O
+possibility	O
+of	O
+recording	O
+up	O
+to	O
+250	O
+diffraction	O
+patterns	O
+with	O
+3	O
+.	O
+5	O
+A	O
+resolution	O
+from	O
+a	O
+single	O
+crotoxin	O
+complex	O
+crystal	O
+128	O
+A	O
+thick	O
+.	O
+
+Supplementary	O
+Phase	O
+Contraste	O
+RSE	O
+(	O
+"	O
+Rapid	O
+Sequential	O
+Excitation	O
+"	O
+)	O
+sequences	O
+were	O
+carried	O
+out	O
+in	O
+29	O
+patients	O
+.	O
+
+In	O
+yeast	O
+,	O
+the	O
+products	O
+of	O
+the	O
+UPF1	B-GENE
+and	O
+UPF3	B-GENE
+genes	I-GENE
+are	O
+required	O
+for	O
+this	O
+decay	O
+pathway	O
+,	O
+and	O
+in	O
+this	O
+report	O
+we	O
+focus	O
+on	O
+the	O
+identification	O
+and	O
+characterization	O
+of	O
+additional	O
+factors	O
+required	O
+for	O
+rapid	O
+decay	O
+of	O
+nonsense	O
+-	O
+containing	O
+mRNAs	O
+.	O
+
+Mutations	O
+in	O
+UPF1	B-GENE
+lead	O
+to	O
+the	O
+selective	O
+stabilization	O
+of	O
+mRNAs	O
+containing	O
+early	O
+nonsense	O
+mutations	O
+without	O
+affecting	O
+the	O
+decay	O
+rates	O
+of	O
+most	O
+other	O
+mRNAs	O
+.	O
+
+A	O
+DNA	O
+fragment	O
+encoding	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+(	O
+amino	O
+acids	O
+1	O
+-	O
+60	O
+)	O
+of	O
+the	O
+Escherichia	B-GENE
+coli	I-GENE
+fru	I-GENE
+transcriptional	I-GENE
+regulator	I-GENE
+was	O
+cloned	O
+into	O
+the	O
+pGEX	O
+-	O
+KT	O
+vector	O
+and	O
+expressed	O
+in	O
+frame	O
+with	O
+the	O
+fused	O
+gene	O
+encoding	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+.	O
+
+0	O
+.	O
+61	O
++	O
+/	O
+-	O
+0	O
+.	O
+04	O
+)	O
+.	O
+
+Several	O
+nuclear	O
+factors	O
+that	O
+interact	O
+with	O
+sequences	O
+in	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+mouse	B-GENE
+tyrosinase	I-GENE
+gene	I-GENE
+were	O
+identified	O
+using	O
+band	O
+shift	O
+and	O
+methylation	O
+interference	O
+assays	O
+.	O
+
+With	O
+a	O
+population	O
+of	O
+853	O
+million	O
+there	O
+should	O
+be	O
+51	O
+,	O
+204	O
+patients	O
+with	O
+hemophilia	O
+A	O
+in	O
+India	O
+assuming	O
+a	O
+prevalence	O
+of	O
+6	O
+/	O
+100	O
+,	O
+000	O
+population	O
+.	O
+
+When	O
+combined	O
+with	O
+serum	O
+ferritin	B-GENE
+and	O
+hemoglobin	B-GENE
+determinations	O
+,	O
+the	O
+serum	O
+transferrin	B-GENE
+receptor	I-GENE
+assay	O
+is	O
+a	O
+valuable	O
+addition	O
+in	O
+epidemiologic	O
+surveys	O
+because	O
+it	O
+provides	O
+a	O
+quantitative	O
+measure	O
+of	O
+functional	O
+iron	O
+deficiency	O
+and	O
+it	O
+distinguishes	O
+true	O
+IDA	O
+from	O
+the	O
+anemia	O
+of	O
+chronic	O
+disease	O
+.	O
+
+Since	O
+1990	O
+the	O
+University	O
+Hospital	O
+of	O
+Tromso	O
+has	O
+provided	O
+local	O
+hospitals	O
+in	O
+northern	O
+Norway	O
+with	O
+a	O
+remote	O
+frozen	O
+section	O
+service	O
+and	O
+with	O
+access	O
+to	O
+video	O
+conferences	O
+for	O
+the	O
+review	O
+of	O
+microscopic	O
+findings	O
+and	O
+for	O
+the	O
+discussion	O
+of	O
+major	O
+diagnostic	O
+issues	O
+.	O
+
+Current	O
+status	O
+of	O
+telepathology	O
+.	O
+
+PMEK1	B-GENE
+displays	O
+96	O
+and	O
+80	O
+%	O
+identity	O
+respectively	O
+with	O
+the	O
+tobacco	B-GENE
+NTF3	I-GENE
+and	O
+Arabidopsis	B-GENE
+ATMPK1	I-GENE
+kinases	I-GENE
+,	O
+and	O
+only	O
+50	O
+%	O
+to	O
+the	O
+more	O
+distantly	O
+related	O
+plant	O
+MAP	O
+kinase	O
+MsERK1	B-GENE
+from	O
+alfalfa	O
+.	O
+
+Translation	O
+of	O
+the	O
+coding	O
+segment	O
+,	O
+which	O
+was	O
+designated	O
+MsPRP2	B-GENE
+,	O
+suggested	O
+it	O
+encodes	O
+a	O
+chimeric	O
+40	O
+,	O
+569	O
+Da	O
+cell	O
+wall	O
+protein	O
+with	O
+an	O
+amino	O
+-	O
+terminal	O
+signal	O
+sequence	O
+,	O
+a	O
+repetitive	O
+proline	O
+-	O
+rich	O
+sequence	O
+,	O
+and	O
+a	O
+cysteine	O
+-	O
+rich	O
+carboxyl	O
+-	O
+terminal	O
+sequence	O
+homologous	O
+to	O
+nonspecific	O
+lipid	O
+transfer	O
+proteins	O
+.	O
+
+The	O
+presence	O
+of	O
+type	O
+I	O
+hypersensitivity	O
+in	O
+a	O
+subgroup	O
+of	O
+aspergillomas	O
+suggests	O
+an	O
+immunoallergic	O
+component	O
+to	O
+this	O
+disease	O
+which	O
+could	O
+contribute	O
+to	O
+a	O
+chronic	O
+inflammatory	O
+response	O
+to	O
+Aspergillus	O
+in	O
+some	O
+aspergillomas	O
+.	O
+
+This	O
+concept	O
+is	O
+supported	O
+by	O
+the	O
+identification	O
+of	O
+RH	B-GENE
+-	I-GENE
+like	I-GENE
+genes	I-GENE
+in	O
+non	O
+human	O
+primates	O
+.	O
+
+With	O
+steady	O
+illumination	O
+,	O
+outer	O
+retinal	O
+(	O
+photoreceptor	O
+)	O
+QO2	O
+decreased	O
+to	O
+1	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+ml	O
+O2	O
+/	O
+(	O
+100	O
+g	O
+.	O
+min	O
+)	O
+,	O
+but	O
+inner	O
+retinal	O
+QO2	O
+remained	O
+unchanged	O
+at	O
+3	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+5	O
+ml	O
+O2	O
+/	O
+(	O
+100	O
+g	O
+.	O
+min	O
+)	O
+(	O
+5	O
+cats	O
+)	O
+.	O
+
+We	O
+have	O
+screened	O
+the	O
+mouse	O
+cDNA	O
+library	O
+of	O
+an	O
+MIN6	O
+cell	O
+line	O
+,	O
+derived	O
+from	O
+pancreatic	O
+beta	O
+cells	O
+,	O
+for	O
+its	O
+novel	O
+isoform	O
+and	O
+have	O
+identified	O
+a	O
+cDNA	O
+encoding	O
+a	O
+593	O
+-	O
+amino	O
+acid	O
+protein	O
+having	O
+63	O
+,	O
+53	O
+,	O
+and	O
+30	O
+%	O
+identity	O
+with	O
+munc	B-GENE
+-	I-GENE
+18	I-GENE
+/	I-GENE
+n	I-GENE
+-	I-GENE
+Sec1	I-GENE
+/	I-GENE
+rbSec1	I-GENE
+,	O
+Caenorhabditis	B-GENE
+elegans	I-GENE
+unc18	I-GENE
+,	O
+and	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+Sec1p	I-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+catenins	B-GENE
+bind	O
+to	O
+APC	B-GENE
+and	O
+E	B-GENE
+-	I-GENE
+cadherin	I-GENE
+in	O
+a	O
+similar	O
+fashion	O
+,	O
+but	O
+APC	B-GENE
+and	O
+E	B-GENE
+-	I-GENE
+cadherin	I-GENE
+do	O
+not	O
+associate	O
+with	O
+each	O
+other	O
+either	O
+in	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+catenins	B-GENE
+.	O
+
+However	O
+,	O
+addition	O
+of	O
+core	B-GENE
+DNA	I-GENE
+polymerase	I-GENE
+III	I-GENE
+to	O
+preinitiation	O
+complex	O
+,	O
+fully	O
+reconstituting	O
+holoenzyme	O
+resulted	O
+in	O
+replacement	O
+of	O
+gamma	O
+by	O
+alpha	O
+at	O
+the	O
+primer	O
+terminus	O
+.	O
+
+Computerized	O
+detection	O
+of	O
+abnormal	O
+asymmetry	O
+in	O
+digital	O
+chest	O
+radiographs	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+gluconeogenic	O
+genes	O
+are	O
+derepressed	O
+upon	O
+binding	O
+of	O
+Cat8p	B-GENE
+,	O
+whose	O
+synthesis	O
+depends	O
+on	O
+the	O
+release	O
+of	O
+Cat4p	B-GENE
+(	O
+Mig1p	B-GENE
+)	O
+from	O
+the	O
+CAT8	B-GENE
+promoter	I-GENE
+.	O
+
+We	O
+show	O
+here	O
+that	O
+the	O
+binding	O
+of	O
+C1F	B-GENE
+in	O
+vitro	O
+is	O
+sensitive	O
+to	O
+the	O
+concentration	O
+of	O
+calcium	O
+ions	O
+.	O
+
+Survival	O
+after	O
+development	O
+of	O
+symptomatic	O
+infection	O
+(	O
+P	O
+-	O
+2	O
+)	O
+did	O
+not	O
+differ	O
+by	O
+transmission	O
+mode	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+the	O
+function	O
+of	O
+the	O
+DS2	B-GENE
+may	O
+be	O
+the	O
+protection	O
+of	O
+the	O
+nuclear	O
+DNA	O
+from	O
+desiccation	O
+.	O
+
+Glomerular	O
+hemodynamics	O
+during	O
+abortion	O
+induced	O
+by	O
+RU	O
+486	O
+and	O
+sepsis	O
+in	O
+rats	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+retrospective	O
+study	O
+was	O
+to	O
+demonstrate	O
+that	O
+in	O
+certain	O
+cases	O
+of	O
+expulsive	O
+choroidal	O
+hemorrhage	O
+(	O
+ECH	O
+)	O
+anatomical	O
+success	O
+and	O
+useful	O
+vision	O
+can	O
+be	O
+obtained	O
+with	O
+repeated	O
+vitreoretinal	O
+surgery	O
+.	O
+
+The	O
+function	O
+of	O
+the	O
+C	O
+-	O
+terminal	O
+tail	O
+in	O
+telomere	O
+maintenance	O
+is	O
+not	O
+mediated	O
+through	O
+the	O
+RAP1	B-GENE
+interacting	I-GENE
+factor	I-GENE
+RIF1	B-GENE
+:	O
+rap1	B-GENE
+alleles	I-GENE
+defective	O
+in	O
+both	O
+the	O
+C	O
+-	O
+terminal	O
+tail	O
+and	O
+RIF1	B-GENE
+interaction	I-GENE
+domains	I-GENE
+have	O
+additive	O
+effects	O
+on	O
+telomere	O
+length	O
+.	O
+
+The	O
+contribution	O
+of	O
+skin	O
+flow	O
+to	O
+the	O
+changes	O
+in	O
+760	O
+-	O
+800	O
+nm	O
+absorption	O
+was	O
+investigated	O
+by	O
+simultaneous	O
+measurement	O
+of	O
+skin	O
+flow	O
+by	O
+laser	O
+flow	O
+Doppler	O
+and	O
+NIR	O
+recordings	O
+during	O
+hot	O
+water	O
+immersion	O
+.	O
+
+Proteins	O
+immunoprecipitated	O
+from	O
+lysates	O
+of	O
+control	O
+-	O
+and	O
+VEGF	B-GENE
+-	O
+stimulated	O
+BAEC	O
+with	O
+antisera	O
+to	O
+phospholipase	B-GENE
+C	I-GENE
+-	I-GENE
+gamma	I-GENE
+(	O
+PLC	B-GENE
+-	I-GENE
+gamma	I-GENE
+)	O
+were	O
+fractionated	O
+by	O
+SDS	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+and	O
+transferred	O
+to	O
+Immobilon	O
+-	O
+P	O
+.	O
+
+Alternatively	O
+processed	O
+isoforms	O
+of	O
+cellular	B-GENE
+nucleic	I-GENE
+acid	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+interact	O
+with	O
+a	O
+suppressor	O
+region	O
+of	O
+the	O
+human	B-GENE
+beta	I-GENE
+-	I-GENE
+myosin	I-GENE
+heavy	I-GENE
+chain	I-GENE
+gene	I-GENE
+.	O
+
+Involvement	O
+of	O
+early	B-GENE
+growth	I-GENE
+response	I-GENE
+factor	I-GENE
+Egr	I-GENE
+-	I-GENE
+1	I-GENE
+in	O
+apolipoprotein	B-GENE
+AI	I-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+The	O
+wild	O
+-	O
+type	O
+and	O
+altered	O
+forms	O
+of	O
+the	O
+F	B-GENE
+protein	I-GENE
+were	O
+expressed	O
+in	O
+BHK	O
+-	O
+21	O
+and	O
+HeLa	O
+T4	O
+cells	O
+by	O
+use	O
+of	O
+the	O
+recombinant	B-GENE
+vaccinia	I-GENE
+virus	I-GENE
+-	I-GENE
+encoding	I-GENE
+T7	I-GENE
+polymerase	I-GENE
+system	O
+.	O
+
+Erythrocyte	B-GENE
+delta	I-GENE
+-	I-GENE
+aminolevulinic	I-GENE
+acid	I-GENE
+dehydratase	I-GENE
+(	O
+ALAD	B-GENE
+)	O
+activity	O
+,	O
+erythrocyte	O
+zinc	O
+protoporphyrin	O
+(	O
+ZPP	O
+)	O
+/	O
+heme	O
+ratio	O
+,	O
+and	O
+urinary	O
+coproporphyrin	O
+(	O
+UC	O
+)	O
+concentration	O
+have	O
+been	O
+employed	O
+as	O
+biological	O
+indicators	O
+of	O
+moderate	O
+-	O
+to	O
+high	O
+-	O
+level	O
+lead	O
+exposure	O
+,	O
+corresponding	O
+to	O
+blood	O
+levels	O
+in	O
+excess	O
+of	O
+50	O
+micrograms	O
+/	O
+dl	O
+,	O
+in	O
+human	O
+subjects	O
+.	O
+
+The	O
+relative	O
+risk	O
+of	O
+graft	O
+loss	O
+after	O
+conversion	O
+to	O
+azathioprine	O
+compared	O
+with	O
+graft	O
+loss	O
+after	O
+conversion	O
+to	O
+azathioprine	O
+compared	O
+with	O
+cyclosporin	O
+maintenance	O
+was	O
+0	O
+.	O
+71	O
+(	O
+0	O
+.	O
+37	O
+-	O
+1	O
+.	O
+38	O
+)	O
+and	O
+the	O
+relative	O
+risk	O
+of	O
+patient	O
+death	O
+was	O
+0	O
+.	O
+57	O
+(	O
+0	O
+.	O
+23	O
+-	O
+1	O
+.	O
+41	O
+)	O
+.	O
+
+The	O
+"	O
+tobacco	O
+issue	O
+"	O
+.	O
+
+The	O
+effect	O
+of	O
+the	O
+Ca	O
+entry	O
+blocker	O
+nitrendipine	O
+,	O
+the	O
+antioxidant	O
+superoxide	B-GENE
+dismutase	I-GENE
+(	O
+SOD	B-GENE
+)	O
+,	O
+and	O
+a	O
+combination	O
+of	O
+nitrendipine	O
+and	O
+superoxide	B-GENE
+dismutase	I-GENE
+on	O
+postischemic	O
+renal	O
+function	O
+was	O
+studied	O
+in	O
+four	O
+groups	O
+(	O
+n	O
+=	O
+24	O
+)	O
+of	O
+rats	O
+.	O
+
+PURPOSE	O
+:	O
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+the	O
+bony	O
+anchorage	O
+of	O
+a	O
+new	O
+implant	O
+(	O
+orderly	O
+wired	O
+surface	O
+effect	O
+with	O
+alloy	O
+Ti	O
+Al	O
+Va	O
+and	O
+ordered	O
+pores	O
+of	O
+488	O
+mu	O
+)	O
+.	O
+
+To	O
+determine	O
+whether	O
+food	O
+and	O
+/	O
+or	O
+water	O
+in	O
+the	O
+gastrointestinal	O
+tract	O
+affects	O
+restitution	O
+of	O
+blood	O
+volume	O
+and	O
+plasma	O
+protein	O
+after	O
+hemorrhage	O
+,	O
+fed	O
+and	O
+24	O
+-	O
+h	O
+-	O
+fasted	O
+awake	O
+rats	O
+received	O
+a	O
+20	O
+ml	O
+.	O
+kg	O
+-	O
+1	O
+x	O
+3	O
+min	O
+-	O
+1	O
+hemorrhage	O
+,	O
+and	O
+restitution	O
+of	O
+blood	O
+volume	O
+was	O
+measured	O
+by	O
+Evans	O
+blue	O
+dye	O
+and	O
+dilution	O
+of	O
+hematocrit	O
+.	O
+
+Cooperative	O
+dimerization	O
+of	O
+paired	B-GENE
+class	O
+homeo	O
+domains	O
+on	O
+DNA	O
+.	O
+
+We	O
+took	O
+advantage	O
+of	O
+the	O
+high	O
+degree	O
+of	O
+aa	O
+sequence	O
+homology	O
+between	O
+DAHPSs	B-GENE
+from	O
+several	O
+species	O
+to	O
+isolate	O
+ARO3	B-GENE
+homologues	I-GENE
+from	O
+the	O
+pathogenic	O
+yeast	O
+Candida	O
+albicans	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+demonstrate	O
+that	O
+BOX	O
+DNA	O
+enhances	O
+transcription	O
+from	O
+the	O
+thymidine	B-GENE
+kinase	I-GENE
+(	O
+TK	B-GENE
+)	O
+promoter	O
+in	O
+various	O
+EC	O
+cells	O
+.	O
+
+Deletion	O
+analyses	O
+of	O
+the	O
+construct	O
+revealed	O
+that	O
+the	O
+transcription	O
+of	O
+BOXF1	B-GENE
+gene	I-GENE
+is	O
+regulated	O
+by	O
+BOX	O
+DNA	O
+,	O
+preferentially	O
+in	O
+undifferentiated	O
+EC	O
+cells	O
+versus	O
+differentiated	O
+cells	O
+.	O
+
+The	O
+presence	O
+of	O
+an	O
+unusual	O
+transcript	O
+possessing	O
+IVS2C	B-GENE
+beta	I-GENE
+1	I-GENE
+at	O
+the	O
+5	O
+'	O
+terminus	O
+suggests	O
+that	O
+cleavage	O
+of	O
+its	O
+splice	O
+acceptor	O
+is	O
+inefficient	O
+or	O
+negatively	O
+regulated	O
+.	O
+
+During	O
+chronic	O
+treatment	O
+,	O
+when	O
+plasma	O
+concentrations	O
+fluctuated	O
+between	O
+23	O
+.	O
+5	O
+ng	O
+.	O
+ml	O
+-	O
+1	O
+at	O
+8	O
+h	O
+and	O
+14	O
+ng	O
+.	O
+ml	O
+-	O
+1	O
+at	O
+24	O
+h	O
+post	O
+-	O
+dosing	O
+,	O
+ST	O
+segment	O
+depression	O
+at	O
+an	O
+individually	O
+comparable	O
+workload	O
+was	O
+significantly	O
+decreased	O
+by	O
+28	O
+%	O
+compared	O
+with	O
+placebo	O
+(	O
+P	O
+<	O
+0	O
+.	O
+005	O
+)	O
+at	O
+both	O
+points	O
+in	O
+time	O
+.	O
+
+Results	O
+from	O
+in	O
+vitro	O
+transcription	O
+-	O
+translation	O
+analysis	O
+and	O
+maxicell	O
+experiments	O
+suggested	O
+that	O
+the	O
+447	O
+-	O
+bp	O
+ORF	O
+was	O
+the	O
+one	O
+being	O
+actively	O
+expressed	O
+.	O
+
+Preliminary	O
+experiments	O
+demonstrated	O
+that	O
+it	O
+was	O
+possible	O
+to	O
+produce	O
+fasD	B-GENE
+mutants	I-GENE
+,	O
+whose	O
+products	O
+remain	O
+functional	O
+for	O
+fimbrial	O
+export	O
+and	O
+assembly	O
+.	O
+
+Evoked	O
+electromyographic	O
+response	O
+to	O
+indirect	O
+supramaximal	O
+stimulation	O
+at	O
+1	O
+Hz	O
+was	O
+monitored	O
+in	O
+ten	O
+adult	O
+goats	O
+under	O
+thiopentone	O
+-	O
+halothane	O
+anaesthesia	O
+.	O
+
+313	O
+,	O
+98	O
+-	O
+102	O
+)	O
+.	O
+
+Group	O
+6	O
+was	O
+given	O
+physostigmine	O
+,	O
+0	O
+.	O
+1	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+,	O
+known	O
+to	O
+inhibit	O
+cholinesterase	B-GENE
+degradation	O
+,	O
+5	O
+min	O
+before	O
+bupivacaine	O
+administration	O
+,	O
+and	O
+Group	O
+7	O
+received	O
+a	O
+combination	O
+of	O
+physostigmine	O
+pretreatment	O
+and	O
+electrical	O
+vagal	O
+stimulation	O
+.	O
+
+To	O
+examine	O
+the	O
+possibility	O
+that	O
+LNNB	O
+performance	O
+of	O
+the	O
+schizophrenic	O
+groups	O
+may	O
+have	O
+been	O
+related	O
+to	O
+neuroleptic	O
+medication	O
+,	O
+analyses	O
+were	O
+completed	O
+on	O
+the	O
+relationship	O
+between	O
+medication	O
+levels	O
+and	O
+LNNB	O
+scores	O
+.	O
+
+ISIS	O
+5	O
+possibilities	O
+.	O
+
+The	O
+use	O
+of	O
+specific	O
+antibodies	O
+allowed	O
+the	O
+identification	O
+of	O
+at	O
+least	O
+RAR	B-GENE
+beta	I-GENE
+in	O
+some	O
+of	O
+the	O
+DNA	O
+-	O
+protein	O
+complexes	O
+,	O
+although	O
+the	O
+four	O
+sequences	O
+bind	O
+single	O
+RARs	B-GENE
+transfected	O
+in	O
+COS	O
+cells	O
+much	O
+less	O
+efficiently	O
+,	O
+or	O
+not	O
+at	O
+all	O
+,	O
+when	O
+compared	O
+to	O
+a	O
+canonical	O
+RAR	B-GENE
+responsive	I-GENE
+element	I-GENE
+.	O
+
+The	O
+present	O
+treatment	O
+strategy	O
+in	O
+progressive	O
+disorders	O
+is	O
+mainly	O
+based	O
+on	O
+the	O
+complementary	O
+effect	O
+of	O
+intensive	O
+radiochemotherapy	O
+,	O
+autologous	O
+stem	O
+-	O
+cell	O
+transplantation	O
+and	O
+the	O
+rational	O
+use	O
+of	O
+cytokines	O
+,	O
+mostly	O
+colony	B-GENE
+-	I-GENE
+stimulating	I-GENE
+factors	I-GENE
+.	O
+
+Our	O
+study	O
+cohorts	O
+consisted	O
+of	O
+15	O
+patients	O
+who	O
+received	O
+SC	O
+rIL	B-GENE
+-	I-GENE
+2	I-GENE
+at	O
+doses	O
+of	O
+4	O
+.	O
+8	O
+-	O
+14	O
+.	O
+4	O
+million	O
+IU	O
+/	O
+m2	O
+/	O
+day	O
+on	O
+5	O
+days	O
+per	O
+week	O
+for	O
+a	O
+total	O
+of	O
+8	O
+weeks	O
+,	O
+20	O
+patients	O
+who	O
+received	O
+rIFN	B-GENE
+-	I-GENE
+alpha	I-GENE
+2b	I-GENE
+at	O
+3	O
+.	O
+0	O
+-	O
+6	O
+.	O
+0	O
+million	O
+U	O
+/	O
+m2	O
+/	O
+day	O
+thrice	O
+weekly	O
+for	O
+a	O
+total	O
+of	O
+6	O
+weeks	O
+,	O
+and	O
+72	O
+patients	O
+who	O
+were	O
+given	O
+SC	O
+rIFN	B-GENE
+-	I-GENE
+alpha	I-GENE
+2b	I-GENE
+at	O
+6	O
+.	O
+0	O
+million	O
+U	O
+/	O
+m2	O
+/	O
+day	O
+thrice	O
+weekly	O
+plus	O
+SC	O
+rIL	B-GENE
+-	I-GENE
+2	I-GENE
+at	O
+14	O
+.	O
+4	O
+-	O
+18	O
+.	O
+0	O
+million	O
+IU	O
+/	O
+m2	O
+/	O
+day	O
+on	O
+days	O
+1	O
+and	O
+2	O
+,	O
+followed	O
+by	O
+4	O
+.	O
+8	O
+million	O
+IU	O
+/	O
+m2	O
+/	O
+day	O
+,	O
+5	O
+days	O
+per	O
+week	O
+for	O
+6	O
+consecutive	O
+weeks	O
+.	O
+
+At	O
+the	O
+MTD	O
+(	O
+8	O
+mg	O
+/	O
+m2	O
+/	O
+day	O
+)	O
+,	O
+the	O
+dose	O
+-	O
+limiting	O
+toxicity	O
+of	O
+this	O
+agent	O
+is	O
+myelosuppression	O
+.	O
+
+Mitogen	O
+-	O
+induced	O
+lymphocyte	O
+proliferation	O
+was	O
+diminished	O
+.	O
+
+A	O
+decanucleotide	O
+promoter	O
+sequence	O
+homologous	O
+to	O
+those	O
+found	O
+in	O
+humans	O
+and	O
+mice	O
+was	O
+located	O
+in	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+of	O
+one	O
+horse	O
+gene	O
+.	O
+
+Some	O
+of	O
+these	O
+targets	O
+were	O
+reported	O
+to	O
+code	O
+for	O
+molecules	O
+involved	O
+in	O
+cell	O
+-	O
+cell	O
+interactions	O
+,	O
+whereas	O
+no	O
+relationship	O
+has	O
+yet	O
+been	O
+demonstrated	O
+between	O
+Hox	B-GENE
+genes	I-GENE
+and	O
+other	O
+transcription	O
+factors	O
+involved	O
+in	O
+determining	O
+and	O
+/	O
+or	O
+maintaining	O
+tissue	O
+specificity	O
+.	O
+
+HER2	B-GENE
+overexpressing	O
+cells	O
+showed	O
+a	O
+single	O
+prominent	O
+DNase	B-GENE
+I	I-GENE
+hypersensitive	O
+site	O
+near	O
+a	O
+conserved	O
+and	O
+hitherto	O
+unrecognized	O
+ets	B-GENE
+response	O
+element	O
+(	O
+GAGGAA	O
+)	O
+,	O
+located	O
+38	O
+bases	O
+down	O
+-	O
+stream	O
+from	O
+the	O
+CAAT	O
+box	O
+and	O
+directly	O
+5	O
+'	O
+of	O
+the	O
+TATA	O
+box	O
+in	O
+the	O
+human	B-GENE
+HER2	I-GENE
+promoter	I-GENE
+.	O
+
+Gel	O
+-	O
+shift	O
+assays	O
+with	O
+nuclear	O
+extracts	O
+and	O
+oligonucleotide	O
+sequences	O
+spanning	O
+the	O
+0	O
+.	O
+125	O
+-	O
+kb	O
+promoter	O
+region	O
+detected	O
+an	O
+ETS	B-GENE
+-	O
+immunoreactive	O
+complex	O
+,	O
+present	O
+most	O
+abundantly	O
+in	O
+cells	O
+overexpressing	O
+HER2	B-GENE
+,	O
+whose	O
+high	O
+-	O
+affinity	O
+binding	O
+depended	O
+on	O
+the	O
+GAGGAA	O
+response	O
+element	O
+.	O
+
+Comparison	O
+of	O
+cDNA	O
+sequences	O
+revealed	O
+that	O
+the	O
+two	O
+mRNA	O
+species	O
+arise	O
+as	O
+a	O
+result	O
+of	O
+alternate	O
+use	O
+of	O
+poly	O
+(	O
+A	O
+)	O
+-	O
+addition	O
+sites	O
+.	O
+
+The	O
+gene	O
+for	O
+the	O
+RNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+eIF	I-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+PKR	B-GENE
+)	O
+was	O
+isolated	O
+from	O
+mouse	O
+genomic	O
+DNA	O
+and	O
+characterized	O
+.	O
+
+High	O
+-	O
+frequency	O
+electrical	O
+stimulation	O
+in	O
+the	O
+hippocampus	O
+leads	O
+to	O
+an	O
+increase	O
+in	O
+synaptic	O
+efficacy	O
+that	O
+lasts	O
+for	O
+many	O
+hours	O
+.	O
+
+Similar	O
+to	O
+the	O
+mouse	O
+gene	O
+,	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+human	B-GENE
+CD79	I-GENE
+alpha	I-GENE
+lacks	O
+a	O
+TATA	O
+box	O
+;	O
+however	O
+,	O
+unlike	O
+mouse	B-GENE
+CD79	I-GENE
+alpha	I-GENE
+,	O
+a	O
+classical	O
+octamer	O
+motif	O
+could	O
+not	O
+be	O
+identified	O
+in	O
+the	O
+human	O
+gene	O
+.	O
+
+Detailed	O
+molecular	O
+organization	O
+of	O
+the	O
+coding	O
+and	O
+upstream	O
+regulatory	O
+regions	O
+of	O
+the	O
+murine	O
+homeodomain	B-GENE
+-	I-GENE
+containing	I-GENE
+gene	I-GENE
+,	O
+Msx	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+is	O
+reported	O
+.	O
+
+We	O
+report	O
+here	O
+the	O
+cloning	O
+of	O
+the	O
+human	B-GENE
+goosecoid	I-GENE
+gene	I-GENE
+(	O
+GSC	B-GENE
+)	O
+from	O
+a	O
+genomic	O
+library	O
+and	O
+the	O
+sequence	O
+of	O
+its	O
+encoded	O
+protein	O
+.	O
+
+This	O
+virus	O
+is	O
+not	O
+merely	O
+a	O
+South	O
+African	O
+strain	O
+of	O
+passion	O
+fruit	O
+woodiness	O
+virus	O
+(	O
+PWV	O
+)	O
+:	O
+the	O
+deduced	O
+CP	B-GENE
+sequence	I-GENE
+is	O
+only	O
+distantly	O
+related	O
+to	O
+CPs	B-GENE
+of	O
+other	O
+sequenced	O
+strains	O
+of	O
+PWV	O
+,	O
+although	O
+it	O
+is	O
+part	O
+of	O
+a	O
+distinct	O
+subgroup	O
+of	O
+potyviruses	O
+related	O
+to	O
+PWV	O
+.	O
+
+The	O
+ratio	O
+of	O
+the	O
+activity	O
+of	O
+arogenate	B-GENE
+dehydrogenase	I-GENE
+to	O
+that	O
+of	O
+prephenate	B-GENE
+dehydrogenase	I-GENE
+(	O
+approximately	O
+3	O
+:	O
+1	O
+)	O
+remained	O
+constant	O
+throughout	O
+purification	O
+,	O
+and	O
+the	O
+two	O
+activities	O
+were	O
+therefore	O
+inseparable	O
+.	O
+
+A	O
+leucine	O
+zipper	O
+domain	O
+of	O
+the	O
+suppressor	B-GENE
+of	I-GENE
+Hairy	I-GENE
+-	I-GENE
+wing	I-GENE
+protein	I-GENE
+mediates	O
+its	O
+repressive	O
+effect	O
+on	O
+enhancer	O
+function	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+CT	O
+should	O
+be	O
+routinely	O
+employed	O
+in	O
+patients	O
+with	O
+N1	O
+-	O
+N3	O
+neck	O
+disease	O
+to	O
+determine	O
+the	O
+proper	O
+electron	O
+-	O
+energy	O
+prescription	O
+.	O
+
+The	O
+predicted	O
+DNA	O
+-	O
+binding	O
+,	O
+zinc	B-GENE
+finger	I-GENE
+domain	I-GENE
+protein	I-GENE
+sequence	O
+was	O
+strictly	O
+conserved	O
+.	O
+
+60	O
+patients	O
+were	O
+entered	O
+into	O
+a	O
+randomised	O
+study	O
+comparing	O
+vindesine	O
+(	O
+3	O
+mg	O
+/	O
+m2	O
+/	O
+week	O
+)	O
+plus	O
+interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+2b	I-GENE
+(	O
+6	O
+U	O
+/	O
+m2	O
+3	O
+times	O
+per	O
+week	O
+)	O
+to	O
+vindesine	O
+alone	O
+or	O
+to	O
+interferon	B-GENE
+alone	O
+for	O
+the	O
+treatment	O
+of	O
+metastatic	O
+malignant	O
+melanoma	O
+.	O
+
+BACKGROUND	O
+:	O
+We	O
+conducted	O
+a	O
+phase	O
+I	O
+study	O
+with	O
+MDL	O
+73	O
+,	O
+147EF	O
+,	O
+a	O
+new	O
+5	B-GENE
+hydroxytryptamine	I-GENE
+3	I-GENE
+(	I-GENE
+5	I-GENE
+-	I-GENE
+HT3	I-GENE
+)	I-GENE
+receptor	I-GENE
+antagonist	O
+,	O
+in	O
+25	O
+patients	O
+requiring	O
+emetogenic	O
+chemotherapy	O
+.	O
+
+In	O
+the	O
+presence	O
+of	O
+the	O
+in	O
+vivo	O
+reducing	O
+system	O
+(	O
+thioredoxin	B-GENE
+,	O
+thioredoxin	B-GENE
+reductase	I-GENE
+,	O
+and	O
+NADPH	O
+)	O
+,	O
+however	O
+,	O
+each	O
+of	O
+these	O
+mutants	O
+catalyzed	O
+the	O
+formation	O
+of	O
+only	O
+0	O
+.	O
+6	O
+-	O
+0	O
+.	O
+8	O
+dCTPs	O
+per	O
+mole	O
+of	O
+enzyme	O
+.	O
+
+These	O
+genetic	O
+alterations	O
+do	O
+not	O
+affect	O
+synthesis	O
+of	O
+the	O
+major	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+protein	I-GENE
+,	O
+p64	B-GENE
+,	O
+which	O
+is	O
+initiated	O
+from	O
+the	O
+first	O
+AUG	O
+codon	O
+in	O
+exon	O
+2	O
+.	O
+
+In	O
+addition	O
+,	O
+both	O
+the	O
+exon	O
+1	O
+-	O
+and	O
+exon	O
+2	O
+-	O
+initiated	O
+forms	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+protein	I-GENE
+stimulated	O
+transcription	O
+of	O
+a	O
+Myc	B-GENE
+/	O
+Max	B-GENE
+-	O
+responsive	O
+reporter	O
+construct	O
+to	O
+a	O
+similar	O
+level	O
+.	O
+
+Biological	O
+activities	O
+of	O
+hematopoietic	B-GENE
+growth	I-GENE
+factors	I-GENE
+that	O
+lead	O
+to	O
+future	O
+clinical	O
+application	O
+.	O
+
+Expression	O
+is	O
+exclusively	O
+limited	O
+to	O
+the	O
+CNS	O
+at	O
+this	O
+and	O
+later	O
+stages	O
+.	O
+
+Disruption	O
+of	O
+any	O
+one	O
+of	O
+the	O
+four	O
+genes	O
+encoding	O
+the	O
+newly	O
+identified	O
+SRP	B-GENE
+proteins	I-GENE
+results	O
+in	O
+slow	O
+cell	O
+growth	O
+and	O
+inefficient	O
+protein	O
+translocation	O
+across	O
+the	O
+ER	O
+membrane	O
+.	O
+
+Genetic	O
+alterations	O
+in	O
+elements	O
+of	O
+normal	O
+signal	O
+transduction	O
+mechanisms	O
+are	O
+known	O
+to	O
+be	O
+oncogenic	O
+events	O
+often	O
+resulting	O
+in	O
+aberrant	O
+activation	O
+of	O
+programs	O
+of	O
+gene	O
+transcription	O
+.	O
+
+The	O
+expression	O
+pattern	O
+of	O
+GL2	B-GENE
+,	O
+as	O
+demonstrated	O
+by	O
+in	O
+situ	O
+hybridization	O
+,	O
+indicated	O
+that	O
+the	O
+gene	O
+is	O
+expressed	O
+in	O
+trichome	O
+progenitor	O
+cells	O
+and	O
+at	O
+stages	O
+associated	O
+with	O
+trichome	O
+development	O
+.	O
+
+NOT4	B-GENE
+interacts	O
+with	O
+NOT1	B-GENE
+and	O
+NOT3	B-GENE
+in	O
+the	O
+two	O
+-	O
+hybrid	O
+assay	O
+,	O
+and	O
+overexpression	O
+of	O
+NOT3	B-GENE
+or	O
+NOT4	B-GENE
+suppresses	O
+not1	B-GENE
+and	O
+not2	B-GENE
+mutations	O
+.	O
+
+Binding	O
+site	O
+selection	O
+using	O
+in	O
+vitro	O
+-	O
+synthesized	O
+proteins	O
+reveals	O
+that	O
+the	O
+ROR	B-GENE
+alpha	I-GENE
+1	I-GENE
+and	O
+ROR	B-GENE
+alpha	I-GENE
+2	I-GENE
+isoforms	I-GENE
+bind	O
+DNA	O
+as	O
+monomers	O
+to	O
+hormone	O
+response	O
+elements	O
+composed	O
+of	O
+a	O
+6	O
+-	O
+bp	O
+AT	O
+-	O
+rich	O
+sequence	O
+preceding	O
+a	O
+half	O
+-	O
+site	O
+core	O
+motif	O
+PuGGTCA	O
+(	O
+RORE	B-GENE
+)	O
+.	O
+
+The	O
+p73pct1	B-GENE
+/	O
+p85cdc10	B-GENE
+complex	O
+binds	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+to	O
+MCB	B-GENE
+but	O
+not	O
+SCB	B-GENE
+or	O
+E2F	B-GENE
+sites	I-GENE
+.	O
+
+We	O
+show	O
+that	O
+the	O
+en	B-GENE
+stripes	O
+expand	O
+anteriorly	O
+in	O
+slp	B-GENE
+mutant	O
+embryos	O
+and	O
+that	O
+slp	B-GENE
+activity	O
+is	O
+an	O
+absolute	O
+requirement	O
+for	O
+maintenance	O
+of	O
+wg	B-GENE
+expression	O
+at	O
+the	O
+same	O
+time	O
+that	O
+wg	B-GENE
+transcription	O
+is	O
+dependent	O
+on	O
+hh	B-GENE
+.	O
+
+The	O
+DNA	O
+sequence	O
+adjacent	O
+to	O
+the	O
+lacZ	B-GENE
+gene	I-GENE
+has	O
+been	O
+determined	O
+for	O
+91	O
+vegetative	O
+fusion	O
+genes	O
+whose	O
+products	O
+have	O
+been	O
+localized	O
+and	O
+for	O
+43	O
+meiotically	O
+induced	O
+fusions	O
+.	O
+
+CMV	O
+hyperimmunoglobulin	B-GENE
+treatment	O
+(	O
+Cytotect	O
+,	O
+Biotest	O
+)	O
+was	O
+started	O
+(	O
+2	O
+ml	O
+/	O
+kg	O
+bw	O
+on	O
+day	O
+1	O
+and	O
+3	O
+,	O
+and	O
+1	O
+ml	O
+/	O
+kg	O
+on	O
+days	O
+5	O
+,	O
+7	O
+and	O
+9	O
+)	O
+,	O
+which	O
+led	O
+to	O
+the	O
+eradication	O
+of	O
+the	O
+residual	O
+infiltrate	O
+and	O
+CMV	O
+-	O
+DNA	O
+in	O
+the	O
+myocardium	O
+.	O
+
+In	O
+eight	O
+groups	O
+of	O
+subjects	O
+operating	O
+various	O
+hand	O
+-	O
+held	O
+vibrating	O
+tools	O
+and	O
+aged	O
+from	O
+30	O
+to	O
+59	O
+years	O
+,	O
+the	O
+prevalence	O
+rates	O
+of	O
+vibration	O
+-	O
+induced	O
+white	O
+finger	O
+(	O
+VWF	O
+)	O
+and	O
+numbness	O
+,	O
+pain	O
+,	O
+or	O
+stiffness	O
+in	O
+the	O
+upper	O
+and	O
+lower	O
+extremities	O
+were	O
+investigated	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+showed	O
+that	O
+the	O
+gene	O
+was	O
+525	O
+bp	O
+long	O
+and	O
+encoded	O
+a	O
+175	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+with	O
+a	O
+molecular	O
+weight	O
+of	O
+19	O
+,	O
+094	O
+containing	O
+a	O
+21	O
+-	O
+residue	O
+typical	O
+lipoprotein	O
+signal	O
+peptide	O
+and	O
+consensus	O
+prolipoprotein	O
+processing	O
+site	O
+.	O
+
+DNA	O
+sequence	O
+and	O
+functions	O
+of	O
+the	O
+actVI	B-GENE
+region	I-GENE
+of	O
+the	O
+actinorhodin	B-GENE
+biosynthetic	I-GENE
+gene	I-GENE
+cluster	I-GENE
+of	I-GENE
+Streptomyces	I-GENE
+coelicolor	I-GENE
+A3	I-GENE
+(	I-GENE
+2	I-GENE
+)	I-GENE
+.	O
+
+(	O
+1992	O
+)	O
+Genomics	O
+12	O
+,	O
+58	O
+-	O
+62	O
+)	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+predicted	O
+polypeptide	O
+sequence	O
+of	O
+the	O
+Drosophila	O
+protein	O
+with	O
+the	O
+equivalent	O
+subunits	O
+from	O
+mouse	O
+and	O
+yeast	O
+suggests	O
+that	O
+they	O
+are	O
+closely	O
+related	O
+and	O
+defines	O
+three	O
+conserved	O
+regions	O
+which	O
+are	O
+likely	O
+to	O
+be	O
+important	O
+for	O
+enzyme	O
+activity	O
+.	O
+
+Cytoplasmic	B-GENE
+dynein	I-GENE
+is	O
+a	O
+multisubunit	O
+,	O
+microtubule	O
+-	O
+dependent	O
+mechanochemical	O
+enzyme	O
+that	O
+has	O
+been	O
+proposed	O
+to	O
+function	O
+in	O
+a	O
+variety	O
+of	O
+intracellular	O
+movements	O
+,	O
+including	O
+minus	O
+-	O
+end	O
+-	O
+directed	O
+transport	O
+of	O
+organelles	O
+.	O
+
+Identification	O
+of	O
+the	O
+plakoglobin	B-GENE
+-	O
+binding	O
+domain	O
+in	O
+desmoglein	B-GENE
+and	O
+its	O
+role	O
+in	O
+plaque	O
+assembly	O
+and	O
+intermediate	O
+filament	O
+anchorage	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+One	O
+hundred	O
+eighty	O
+-	O
+four	O
+chemotherapy	O
+-	O
+naive	O
+patients	O
+receiving	O
+high	O
+-	O
+dose	O
+cisplatin	O
+(	O
+81	O
+to	O
+120	O
+mg	O
+/	O
+m2	O
+)	O
+were	O
+randomized	O
+to	O
+receive	O
+one	O
+of	O
+four	O
+granisetron	O
+doses	O
+(	O
+5	O
+,	O
+10	O
+,	O
+20	O
+,	O
+or	O
+40	O
+micrograms	O
+/	O
+kg	O
+)	O
+administered	O
+before	O
+chemotherapy	O
+.	O
+
+Nine	O
+new	O
+naphthalene	O
+related	O
+compounds	O
+(	O
+I	O
+,	O
+IV	O
+,	O
+V	O
+,	O
+VII	O
+-	O
+XII	O
+)	O
+together	O
+with	O
+four	O
+known	O
+compounds	O
+(	O
+II	O
+,	O
+III	O
+,	O
+VI	O
+,	O
+XIII	O
+)	O
+were	O
+isolated	O
+from	O
+the	O
+root	O
+bark	O
+of	O
+Oroxylum	O
+indicum	O
+Vent	O
+.	O
+
+As	O
+shown	O
+previously	O
+,	O
+EBNA2	B-GENE
+transactivates	O
+the	O
+promoters	O
+of	O
+the	O
+viral	B-GENE
+latent	I-GENE
+membrane	I-GENE
+proteins	I-GENE
+.	O
+
+We	O
+previously	O
+showed	O
+that	O
+v	B-GENE
+-	I-GENE
+Rel	I-GENE
+,	O
+the	O
+oncoprotein	O
+of	O
+the	O
+avian	O
+retrovirus	O
+Rev	O
+-	O
+T	O
+,	O
+can	O
+increase	O
+expression	O
+from	O
+promoters	O
+containing	O
+binding	O
+sites	O
+for	O
+the	O
+cellular	O
+transcription	O
+factor	O
+Sp1	B-GENE
+in	O
+chicken	O
+embryo	O
+fibroblasts	O
+(	O
+S	O
+.	O
+
+Previous	O
+studies	O
+have	O
+demonstrated	O
+that	O
+the	O
+TATA	O
+element	O
+is	O
+critical	O
+for	O
+basal	O
+and	O
+Tat	B-GENE
+-	O
+induced	O
+HIV	O
+-	O
+1	O
+gene	O
+expression	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+p54	B-GENE
+gene	I-GENE
+carried	O
+by	O
+two	O
+virulent	O
+ASFV	O
+strains	O
+(	O
+E70	O
+and	O
+E75	O
+)	O
+with	O
+that	O
+obtained	O
+from	O
+virus	O
+Ba71V	O
+showed	O
+100	O
+%	O
+similarity	O
+.	O
+
+The	O
+p55	B-GENE
+mRNA	I-GENE
+is	O
+undetectable	O
+in	O
+non	O
+-	O
+EBV	O
+-	O
+infected	O
+B	O
+-	O
+and	O
+T	O
+-	O
+cell	O
+lines	O
+or	O
+in	O
+a	O
+myelomonocytic	O
+cell	O
+line	O
+(	O
+U937	O
+)	O
+.	O
+
+A	O
+simple	O
+registration	O
+as	O
+an	O
+incentive	O
+for	O
+improvement	O
+
+RESULTS	O
+:	O
+The	O
+diagnostic	O
+quality	O
+of	O
+FDG	O
+images	O
+was	O
+at	O
+least	O
+as	O
+good	O
+as	O
+that	O
+of	O
+their	O
+Tl	O
+-	O
+201	O
+counterparts	O
+,	O
+with	O
+less	O
+liver	O
+background	O
+in	O
+all	O
+but	O
+one	O
+FDG	O
+study	O
+.	O
+
+The	O
+coordinated	O
+expression	O
+of	O
+CD4	B-GENE
+and	O
+CD8	B-GENE
+during	O
+T	O
+-	O
+cell	O
+development	O
+is	O
+tightly	O
+coupled	O
+with	O
+the	O
+maturation	O
+state	O
+of	O
+the	O
+T	O
+cell	O
+.	O
+
+The	O
+dying	O
+tTG	B-GENE
+-	O
+transfected	O
+cells	O
+exhibit	O
+both	O
+cytoplasmic	O
+and	O
+nuclear	O
+changes	O
+characteristic	O
+of	O
+cells	O
+undergoing	O
+apoptosis	O
+.	O
+
+Using	O
+an	O
+RNase	B-GENE
+H	I-GENE
+-	O
+mediated	O
+mapping	O
+technique	O
+,	O
+we	O
+show	O
+that	O
+the	O
+64	O
+-	O
+kDa	O
+subunit	O
+of	O
+CstF	B-GENE
+can	O
+be	O
+photo	O
+cross	O
+-	O
+linked	O
+to	O
+pre	O
+-	O
+mRNAs	O
+at	O
+U	O
+-	O
+rich	O
+regions	O
+located	O
+downstream	O
+of	O
+the	O
+cleavage	O
+site	O
+of	O
+the	O
+simian	O
+virus	O
+40	O
+late	O
+and	O
+adenovirus	B-GENE
+L3	I-GENE
+pre	I-GENE
+-	I-GENE
+mRNAs	I-GENE
+.	O
+
+The	O
+protein	O
+encoded	O
+is	O
+114	O
+kDa	O
+and	O
+contains	O
+eight	O
+zinc	O
+finger	O
+motifs	O
+,	O
+seven	O
+of	O
+which	O
+are	O
+present	O
+in	O
+two	O
+clusters	O
+at	O
+opposite	O
+ends	O
+of	O
+the	O
+molecule	O
+.	O
+
+Tissue	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+diazepam	B-GENE
+-	I-GENE
+binding	I-GENE
+inhibitor	I-GENE
+in	O
+Drosophila	O
+melanogaster	O
+:	O
+cloning	O
+,	O
+structure	O
+,	O
+and	O
+localization	O
+of	O
+the	O
+gene	O
+.	O
+
+Using	O
+a	O
+v	B-GENE
+-	I-GENE
+erbA	I-GENE
+probe	O
+,	O
+we	O
+obtained	O
+a	O
+cDNA	O
+which	O
+encodes	O
+a	O
+novel	O
+445	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+,	O
+RLD	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+that	O
+contains	O
+the	O
+characteristic	O
+domains	O
+of	O
+nuclear	O
+receptors	O
+.	O
+
+Only	O
+two	O
+of	O
+the	O
+isoforms	O
+possess	O
+the	O
+N	O
+-	O
+terminal	O
+zinc	O
+finger	O
+domain	O
+that	O
+is	O
+necessary	O
+and	O
+sufficient	O
+for	O
+TdT	B-GENE
+promoter	I-GENE
+binding	O
+.	O
+
+This	O
+study	O
+provides	O
+direct	O
+evidence	O
+that	O
+USF	B-GENE
+,	O
+a	O
+member	O
+of	O
+the	O
+basic	B-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+family	I-GENE
+,	O
+binds	O
+to	O
+MLE1	B-GENE
+,	O
+HF	B-GENE
+-	I-GENE
+1a	I-GENE
+,	O
+and	O
+PRE	B-GENE
+B	I-GENE
+sites	I-GENE
+and	O
+suggests	O
+that	O
+it	O
+is	O
+a	O
+component	O
+of	O
+protein	O
+complexes	O
+that	O
+may	O
+coordinately	O
+control	O
+the	O
+expression	O
+of	O
+MLC	B-GENE
+-	I-GENE
+2v	I-GENE
+and	O
+alpha	B-GENE
+-	I-GENE
+myosin	I-GENE
+heavy	I-GENE
+-	I-GENE
+chain	I-GENE
+genes	I-GENE
+.	O
+
+Activation	O
+of	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+gene	I-GENE
+expression	O
+by	O
+a	O
+kinase	O
+-	O
+deficient	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+.	O
+
+Because	O
+endogenous	O
+HSF	B-GENE
+DNA	O
+-	O
+binding	O
+activity	O
+is	O
+low	O
+and	O
+anti	B-GENE
+-	I-GENE
+hHSF1	I-GENE
+antibody	I-GENE
+does	O
+not	O
+recognize	O
+Xenopus	B-GENE
+HSF	I-GENE
+,	O
+we	O
+employed	O
+this	O
+system	O
+for	O
+mapping	O
+regions	O
+in	O
+hHSF1	B-GENE
+that	O
+are	O
+required	O
+for	O
+the	O
+maintenance	O
+of	O
+the	O
+monomeric	O
+state	O
+.	O
+
+Enhancers	O
+containing	O
+disrupted	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+sites	I-GENE
+were	O
+tested	O
+in	O
+transient	O
+expression	O
+assays	O
+in	O
+the	O
+murine	O
+T	O
+-	O
+cell	O
+line	O
+EL4	O
+.	O
+E1	O
+;	O
+alterations	O
+in	O
+the	O
+LVb	O
+element	O
+affected	O
+constitutive	O
+enhancer	O
+activity	O
+,	O
+while	O
+mutation	O
+of	O
+either	O
+the	O
+LVb	O
+or	O
+LVc	O
+element	O
+disrupted	O
+phorbol	O
+ester	O
+-	O
+induced	O
+enhancer	O
+activity	O
+.	O
+
+The	O
+predominant	O
+binding	O
+activity	O
+was	O
+not	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+but	O
+rather	O
+two	O
+independent	O
+DNA	O
+-	O
+protein	O
+complexes	O
+that	O
+comigrated	O
+in	O
+mobility	O
+shift	O
+assays	O
+.	O
+
+Treatment	O
+with	O
+amphotericin	O
+B	O
+and	O
+flucytosine	O
+led	O
+to	O
+improvement	O
+of	O
+the	O
+symptoms	O
+but	O
+did	O
+not	O
+eradicate	O
+the	O
+micro	O
+-	O
+organisms	O
+from	O
+the	O
+cerebrospinal	O
+fluid	O
+(	O
+CSF	O
+)	O
+.	O
+
+The	O
+unexpected	O
+presence	O
+of	O
+the	O
+tRNA	B-GENE
+(	I-GENE
+trp	I-GENE
+)	I-GENE
+(	I-GENE
+CCA	I-GENE
+)	I-GENE
+-	I-GENE
+gene	I-GENE
+transcript	I-GENE
+in	I-GENE
+mitochondria	I-GENE
+is	O
+also	O
+reported	O
+.	O
+
+The	O
+parameters	O
+of	O
+nonspecific	O
+humoral	O
+immunity	O
+-	O
+-	O
+serum	B-GENE
+immunoglobulins	I-GENE
+and	O
+immune	O
+complexes	O
+-	O
+-	O
+were	O
+evaluated	O
+in	O
+irradiated	O
+group	O
+of	O
+patients	O
+with	O
+uterine	O
+cervix	O
+carcinoma	O
+(	O
+Stages	O
+IIB	O
+and	O
+IIIB	O
+)	O
+,	O
+during	O
+one	O
+year	O
+follow	O
+up	O
+.	O
+
+Mutation	O
+of	O
+KRKR	O
+to	O
+NGER	O
+retains	O
+MO15	B-GENE
+in	O
+the	O
+cytoplasmic	O
+compartment	O
+,	O
+whilst	O
+the	O
+wild	O
+-	O
+type	O
+protein	O
+is	O
+detected	O
+exclusively	O
+in	O
+the	O
+nucleus	O
+.	O
+
+To	O
+confirm	O
+the	O
+binding	O
+of	O
+protein	O
+to	O
+these	O
+sites	O
+in	O
+cells	O
+,	O
+we	O
+carried	O
+out	O
+an	O
+in	O
+vivo	O
+genomic	O
+footprinting	O
+analysis	O
+of	O
+this	O
+portion	O
+of	O
+the	O
+TGF	B-GENE
+alpha	I-GENE
+promoter	I-GENE
+in	O
+normal	O
+and	O
+transformed	O
+rat	O
+liver	O
+epithelial	O
+cell	O
+lines	O
+that	O
+express	O
+the	O
+endogenous	O
+gene	O
+at	O
+varying	O
+levels	O
+.	O
+
+Strikingly	O
+,	O
+this	O
+subdomain	O
+is	O
+also	O
+present	O
+in	O
+the	O
+otherwise	O
+unrelated	O
+N	O
+-	O
+terminal	O
+activating	O
+region	O
+of	O
+p58c	B-GENE
+-	I-GENE
+ets	I-GENE
+-	I-GENE
+2	I-GENE
+and	O
+was	O
+thus	O
+named	O
+BEC	B-GENE
+for	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+beta	I-GENE
+/	O
+Ets	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+Conserved	I-GENE
+sequence	I-GENE
+.	O
+
+This	O
+work	O
+unravels	O
+a	O
+new	O
+model	O
+for	O
+the	O
+ets	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+ets	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+'	O
+s	O
+evolution	O
+,	O
+based	O
+for	O
+the	O
+first	O
+time	O
+on	O
+both	O
+structural	O
+and	O
+functional	O
+evidences	O
+.	O
+
+The	O
+v	B-GENE
+-	I-GENE
+ets	I-GENE
+oncogene	I-GENE
+of	O
+the	O
+avian	O
+retrovirus	O
+E26	O
+differs	O
+from	O
+its	O
+cellular	O
+progenitor	O
+p68c	B-GENE
+-	I-GENE
+ets	I-GENE
+-	I-GENE
+1	I-GENE
+by	O
+two	O
+amino	O
+acid	O
+substitutions	O
+(	O
+alanine	O
+285	O
+and	O
+isoleucine	O
+445	O
+in	O
+c	B-GENE
+-	I-GENE
+ets	I-GENE
+-	I-GENE
+1	I-GENE
+both	O
+substituted	O
+by	O
+valine	O
+in	O
+v	B-GENE
+-	I-GENE
+ets	I-GENE
+,	O
+mutations	O
+A	O
+and	O
+B	O
+respectively	O
+)	O
+and	O
+its	O
+carboxy	O
+-	O
+terminal	O
+end	O
+(	O
+mutation	O
+C	O
+)	O
+.	O
+
+Consequently	O
+functional	O
+mRNAs	O
+can	O
+be	O
+produced	O
+by	O
+endogenous	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+I	O
+.	O
+
+The	O
+individual	O
+subunits	O
+of	O
+Ku	B-GENE
+have	O
+been	O
+difficult	O
+to	O
+isolate	O
+from	O
+human	O
+cells	O
+without	O
+denaturation	O
+and	O
+attempts	O
+to	O
+produce	O
+functional	B-GENE
+recombinant	I-GENE
+Ku	I-GENE
+have	O
+been	O
+largely	O
+unsuccessful	O
+.	O
+
+Using	O
+this	O
+method	O
+,	O
+we	O
+were	O
+able	O
+to	O
+select	O
+strong	O
+enhancer	O
+-	O
+type	O
+activation	O
+domains	O
+from	O
+the	O
+immediate	B-GENE
+early	I-GENE
+regions	I-GENE
+of	O
+two	O
+herpesviruses	O
+,	O
+namely	O
+pseudorabies	O
+virus	O
+and	O
+bovine	O
+herpesvirus	O
+1	O
+.	O
+
+A	O
+genetic	O
+system	O
+was	O
+devised	O
+to	O
+select	O
+for	O
+pi	B-GENE
+protein	I-GENE
+mutants	I-GENE
+which	O
+discriminate	O
+between	O
+IR	O
+and	O
+DR	O
+(	O
+York	O
+et	O
+al	O
+.	O
+,	O
+Gene	O
+(	O
+Amst	O
+.	O
+)	O
+116	O
+,	O
+7	O
+-	O
+12	O
+,	O
+1992	O
+;	O
+York	O
+and	O
+Filutowicz	O
+,	O
+J	O
+.	O
+
+Univariate	O
+statistical	O
+analysis	O
+based	O
+on	O
+Kaplan	O
+-	O
+Meier	O
+-	O
+estimates	O
+and	O
+Log	O
+-	O
+Rank	O
+-	O
+Test	O
+showed	O
+the	O
+following	O
+prognostically	O
+beneficial	O
+factors	O
+:	O
+Limited	O
+disease	O
+stage	O
+(	O
+p	O
+=	O
+0	O
+.	O
+009	O
+)	O
+,	O
+NSE	B-GENE
+serum	O
+level	O
+less	O
+than	O
+25	O
+micrograms	O
+/	O
+l	O
+(	O
+p	O
+=	O
+0	O
+.	O
+016	O
+)	O
+,	O
+serum	O
+alkaline	B-GENE
+phosphatase	I-GENE
+less	O
+than	O
+200	O
+U	O
+/	O
+l	O
+(	O
+p	O
+=	O
+0	O
+.	O
+035	O
+)	O
+,	O
+normal	O
+serum	O
+albumin	B-GENE
+(	O
+p	O
+=	O
+0	O
+.	O
+003	O
+)	O
+and	O
+activity	O
+index	O
+of	O
+minimum	O
+of	O
+70	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+HBx	B-GENE
+strongly	O
+elevates	O
+levels	O
+of	O
+GTP	O
+-	O
+bound	O
+Ras	B-GENE
+,	O
+activated	O
+and	O
+phosphorylated	O
+Raf	B-GENE
+,	O
+and	O
+tyrosine	O
+-	O
+phosphorylated	O
+and	O
+activated	O
+MAP	B-GENE
+kinase	I-GENE
+.	O
+
+Role	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+in	O
+simian	B-GENE
+virus	I-GENE
+40	I-GENE
+large	I-GENE
+tumor	I-GENE
+antigen	I-GENE
+-	O
+induced	O
+DNA	O
+synthesis	O
+in	O
+quiescent	O
+3T3	O
+-	O
+L1	O
+mouse	O
+fibroblasts	O
+.	O
+
+Laser	O
+therapy	O
+of	O
+penile	O
+carcinoma	O
+
+A	O
+15	O
+.	O
+1	O
+kb	O
+fragment	O
+of	O
+the	O
+yeast	O
+genome	O
+was	O
+allocated	O
+to	O
+the	O
+centromeric	O
+region	O
+of	O
+chromosome	O
+XIV	O
+by	O
+genetic	O
+mapping	O
+.	O
+
+A	O
+third	O
+one	O
+is	O
+homologous	O
+in	O
+half	O
+of	O
+its	O
+length	O
+to	O
+the	O
+prokaryotic	B-GENE
+hydantoinase	I-GENE
+HyuA	B-GENE
+and	O
+in	O
+the	O
+other	O
+half	O
+to	O
+hydatoinase	B-GENE
+HyuB	B-GENE
+.	O
+
+It	O
+was	O
+shown	O
+that	O
+estradiol	O
+concentrations	O
+obtained	O
+after	O
+estradiol	O
+valerate	O
+and	O
+micronized	O
+estradiol	O
+ingestion	O
+were	O
+dependent	O
+on	O
+the	O
+patient	O
+'	O
+s	O
+age	O
+as	O
+well	O
+as	O
+on	O
+the	O
+constitutional	O
+type	O
+.	O
+
+Constipation	O
+is	O
+not	O
+a	O
+risk	O
+factor	O
+for	O
+hemorrhoids	O
+:	O
+a	O
+case	O
+-	O
+control	O
+study	O
+of	O
+potential	O
+etiological	O
+agents	O
+.	O
+
+Of	O
+419	O
+persons	O
+surveyed	O
+,	O
+207	O
+(	O
+49	O
+.	O
+4	O
+%	O
+)	O
+were	O
+antigen	O
+-	O
+positive	O
+with	O
+the	O
+Og4C3	B-GENE
+assay	O
+.	O
+
+Vibrio	O
+cholerae	O
+O139	O
+in	O
+Calcutta	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+the	O
+zebrafish	B-GENE
+egr1	I-GENE
+coding	I-GENE
+region	I-GENE
+revealed	O
+a	O
+high	O
+level	O
+of	O
+homology	O
+to	O
+the	O
+mouse	O
+,	O
+rat	O
+,	O
+and	O
+human	B-GENE
+Egr1	I-GENE
+genes	I-GENE
+with	O
+the	O
+notable	O
+exception	O
+of	O
+a	O
+polymorphic	O
+,	O
+triplet	O
+nucleotide	O
+repeat	O
+sequence	O
+in	O
+the	O
+region	O
+coding	O
+for	O
+the	O
+amino	O
+terminus	O
+of	O
+the	O
+Egr1	B-GENE
+protein	I-GENE
+.	O
+
+The	O
+fibrinogen	B-GENE
+,	O
+serum	O
+proteins	O
+,	O
+sodium	O
+heparin	O
+and	O
+membrane	O
+contributed	O
+to	O
+Cm	O
+by	O
+20	O
+%	O
+,	O
+14	O
+%	O
+,	O
+2	O
+%	O
+and	O
+64	O
+%	O
+,	O
+respectively	O
+.	O
+
+In	O
+these	O
+vectors	O
+the	O
+chimeric	B-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+(	O
+chLTR	B-GENE
+)	O
+drives	O
+the	O
+expression	O
+of	O
+the	O
+chloramphenicol	B-GENE
+acetyl	I-GENE
+transferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+reporter	O
+gene	O
+that	O
+is	O
+followed	O
+by	O
+an	O
+internal	O
+SV40	B-GENE
+virus	I-GENE
+early	I-GENE
+region	I-GENE
+promoter	I-GENE
+linked	O
+to	O
+the	O
+neomycin	B-GENE
+phosphotransferase	I-GENE
+II	I-GENE
+(	O
+NEO	B-GENE
+)	O
+gene	O
+.	O
+
+Optima	O
+)	O
+genomic	O
+library	O
+by	O
+hybridizing	O
+with	O
+elicitor	O
+-	O
+induced	O
+stilbene	B-GENE
+synthase	I-GENE
+cDNA	I-GENE
+as	O
+a	O
+probe	O
+.	O
+
+A	O
+total	O
+of	O
+125	O
+acute	O
+leukemia	O
+adult	O
+patients	O
+were	O
+autografted	O
+with	O
+bone	O
+marrow	O
+(	O
+BM	O
+)	O
+purged	O
+by	O
+mafosfamide	O
+(	O
+ASTA	O
+Z	O
+)	O
+during	O
+the	O
+period	O
+of	O
+January	O
+1983	O
+to	O
+January	O
+1993	O
+.	O
+
+The	O
+pretransplant	O
+regimen	O
+consisted	O
+of	O
+cyclophosphamide	O
+(	O
+120	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+total	O
+body	O
+irradiation	O
+.	O
+
+The	O
+site	O
+-	O
+directed	O
+mutation	O
+of	O
+the	O
+kappa	B-GENE
+B	I-GENE
+motif	I-GENE
+in	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+/	O
+CAT	B-GENE
+plasmid	O
+resulted	O
+in	O
+the	O
+complete	O
+abrogation	O
+of	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+promoter	I-GENE
+activity	O
+in	O
+these	O
+cells	O
+.	O
+
+Curiously	O
+,	O
+testololactone	O
+was	O
+earlier	O
+and	O
+more	O
+widely	O
+used	O
+than	O
+aminoglutethimide	O
+in	O
+treating	O
+advanced	O
+breast	O
+carcinoma	O
+.	O
+
+Use	O
+of	O
+the	O
+vena	O
+cava	O
+to	O
+extend	O
+the	O
+right	O
+renal	O
+vein	O
+for	O
+cadaver	O
+transplantation	O
+is	O
+controversial	O
+.	O
+
+Enhanced	O
+hepatic	O
+portal	O
+blood	O
+flow	O
+induced	O
+by	O
+prostaglandin	O
+E1	O
+following	O
+liver	O
+transplantation	O
+in	O
+pigs	O
+.	O
+
+One	O
+gene	O
+appears	O
+ubiquitously	O
+expressed	O
+while	O
+the	O
+other	O
+is	O
+prominently	O
+expressed	O
+in	O
+muscle	O
+.	O
+
+For	O
+HeLa	O
+,	O
+293	O
+,	O
+U937	O
+,	O
+and	O
+A549	O
+cells	O
+,	O
+participation	O
+of	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+DP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+cyclin	B-GENE
+A	I-GENE
+,	O
+and	O
+RB	B-GENE
+was	O
+involved	O
+in	O
+formation	O
+of	O
+some	O
+complexes	O
+only	O
+,	O
+assuming	O
+participation	O
+of	O
+factors	O
+different	O
+from	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+or	O
+DP	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+others	O
+.	O
+
+E1A	B-GENE
+autoactivation	O
+mediated	O
+by	O
+these	O
+sites	O
+was	O
+about	O
+twofold	O
+compared	O
+with	O
+a	O
+ninefold	O
+activation	O
+described	O
+for	O
+the	O
+complete	O
+E1A	B-GENE
+promoter	I-GENE
+.	O
+
+Cestode	O
+invasion	O
+in	O
+irradiated	O
+host	O
+organism	O
+increases	O
+the	O
+negative	O
+effect	O
+of	O
+ionizing	O
+radiation	O
+on	O
+the	O
+hamster	O
+immune	O
+system	O
+.	O
+
+During	O
+heat	O
+exposure	O
+,	O
+chicks	O
+that	O
+had	O
+been	O
+subjected	O
+to	O
+early	O
+60	O
+%	O
+restriction	O
+with	O
+non	O
+-	O
+metyrapone	O
+-	O
+treated	O
+food	O
+had	O
+lower	O
+H	O
+/	O
+L	O
+ratios	O
+and	O
+improved	O
+resistance	O
+to	O
+marble	O
+spleen	O
+disease	O
+infection	O
+.	O
+
+Analyses	O
+of	O
+additional	O
+tumors	O
+induced	O
+in	O
+mice	O
+from	O
+two	O
+reciprocal	O
+crosses	O
+,	O
+A	O
+/	O
+J	O
+x	O
+C3H	O
+/	O
+HeJ	O
+F1	O
+(	O
+hereafter	O
+called	O
+AC3F1	O
+)	O
+and	O
+C3H	O
+/	O
+HeJ	O
+x	O
+A	O
+/	O
+J	O
+F1	O
+(	O
+hereafter	O
+called	O
+C3AF1	O
+)	O
+,	O
+provided	O
+evidence	O
+for	O
+the	O
+inactivation	O
+of	O
+one	O
+allele	O
+of	O
+the	O
+putative	O
+chromosome	O
+4	O
+tumor	O
+suppressor	O
+gene	O
+by	O
+parental	O
+imprinting	O
+.	O
+
+ERV1	B-GENE
+is	O
+involved	O
+in	O
+the	O
+cell	O
+-	O
+division	O
+cycle	O
+and	O
+the	O
+maintenance	O
+of	O
+mitochondrial	O
+genomes	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Lesion	O
+diameters	O
+of	O
+greater	O
+than	O
+20	O
+mm	O
+and	O
+the	O
+large	O
+sessile	O
+-	O
+type	O
+configurations	O
+were	O
+factors	O
+that	O
+were	O
+associated	O
+with	O
+incomplete	O
+removal	O
+.	O
+
+Routinely	O
+collected	O
+,	O
+processed	O
+and	O
+stored	O
+breast	O
+cancer	O
+tissue	O
+blocks	O
+recovered	O
+from	O
+the	O
+archives	O
+of	O
+the	O
+Pathology	O
+laboratory	O
+in	O
+Dar	O
+es	O
+Salaam	O
+after	O
+storage	O
+of	O
+up	O
+to	O
+3	O
+years	O
+were	O
+analysed	O
+by	O
+a	O
+flow	O
+cytometry	O
+for	O
+DNA	O
+ploidy	O
+and	O
+S	O
+-	O
+phase	O
+fraction	O
+.	O
+
+Cbf3	B-GENE
+contains	O
+three	O
+proteins	O
+,	O
+Cbf3a	B-GENE
+,	O
+Cbf3b	B-GENE
+and	O
+Cbf3c	B-GENE
+.	O
+
+Such	O
+an	O
+interaction	O
+could	O
+be	O
+detected	O
+using	O
+a	O
+GST	B-GENE
+-	O
+POU	B-GENE
+fusion	O
+protein	O
+bound	O
+to	O
+glutathione	O
+-	O
+agarose	O
+beads	O
+.	O
+
+These	O
+mutations	O
+are	O
+localized	O
+in	O
+the	O
+same	O
+region	O
+where	O
+the	O
+HSV	B-GENE
+transactivator	I-GENE
+VP16	I-GENE
+binds	O
+,	O
+but	O
+did	O
+not	O
+coincide	O
+with	O
+the	O
+VP16	B-GENE
+contacts	O
+.	O
+
+Notably	O
+,	O
+these	O
+residues	O
+are	O
+located	O
+in	O
+different	O
+domains	O
+.	O
+
+However	O
+,	O
+rapamycin	O
+inhibited	O
+proliferation	O
+of	O
+Ba	O
+/	O
+F3	O
+-	O
+EpoRgp55	O
+but	O
+not	O
+of	O
+MEL	O
+cells	O
+despite	O
+inhibition	O
+of	O
+p70	B-GENE
+S6	I-GENE
+kinase	I-GENE
+activity	O
+in	O
+both	O
+cells	O
+.	O
+
+Intraventricular	O
+injection	O
+of	O
+(	O
+2S	O
+,	O
+1	O
+'	O
+R	O
+,	O
+2	O
+'	O
+R	O
+,	O
+3	O
+'	O
+R	O
+)	O
+-	O
+2	O
+-	O
+(	O
+2	O
+,	O
+3	O
+-	O
+dicarboxycyclopropyl	O
+)	O
+glycine	O
+(	O
+DCG	O
+-	O
+IV	O
+)	O
+,	O
+a	O
+potent	O
+agonist	O
+for	O
+metabotropic	O
+glutamate	B-GENE
+receptors	I-GENE
+,	O
+to	O
+rats	O
+retarded	O
+dose	O
+-	O
+dependently	O
+the	O
+recovery	O
+from	O
+halothane	O
+anesthesia	O
+at	O
+a	O
+dose	O
+range	O
+from	O
+30	O
+to	O
+300	O
+pmol	O
+/	O
+rat	O
+.	O
+
+The	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factor	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+/	O
+forkhead	B-GENE
+(	O
+fkh	B-GENE
+)	O
+proteins	O
+consist	O
+of	O
+an	O
+extensive	O
+family	O
+of	O
+tissue	O
+-	O
+specific	O
+and	O
+developmental	O
+gene	O
+regulators	O
+which	O
+share	O
+homology	O
+within	O
+the	O
+winged	O
+helix	O
+DNA	O
+binding	O
+motif	O
+.	O
+
+Interestingly	O
+,	O
+dTFIIA	B-GENE
+-	I-GENE
+L	I-GENE
+/	I-GENE
+S	I-GENE
+is	O
+also	O
+able	O
+to	O
+significantly	O
+enhance	O
+transcriptional	O
+activation	O
+by	O
+upstream	O
+transcription	O
+factors	O
+including	O
+Sp1	B-GENE
+,	O
+VP16	B-GENE
+,	O
+and	O
+NTF	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+particular	O
+,	O
+changes	O
+in	O
+intracellular	O
+Ca2	O
++	O
+have	O
+the	O
+potential	O
+to	O
+either	O
+inhibit	O
+or	O
+augment	O
+the	O
+ability	O
+of	O
+cAMP	O
+to	O
+stimulate	O
+transcription	O
+,	O
+depending	O
+on	O
+the	O
+presence	O
+of	O
+specific	O
+forms	O
+of	O
+Ca2	B-GENE
++	I-GENE
+/	I-GENE
+calmodulin	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinases	I-GENE
+.	O
+
+Antibodies	O
+directed	O
+against	O
+the	O
+SNM1	B-GENE
+protein	I-GENE
+immunoprecipitated	O
+RNase	B-GENE
+MRP	I-GENE
+RNA	I-GENE
+from	O
+whole	O
+-	O
+cell	O
+extracts	O
+without	O
+precipitating	O
+the	O
+structurally	O
+and	O
+functionally	O
+related	O
+RNase	B-GENE
+P	I-GENE
+RNA	I-GENE
+.	O
+
+Our	O
+results	O
+show	O
+that	O
+the	O
+ORF	O
+of	O
+hAMPK	B-GENE
+encodes	O
+552	O
+amino	O
+acids	O
+(	O
+aa	O
+)	O
+(	O
+62	O
+.	O
+250	O
+kDa	O
+)	O
+and	O
+is	O
+highly	O
+conserved	O
+with	O
+rAMPK	B-GENE
+with	O
+identities	O
+of	O
+97	O
+.	O
+3	O
+and	O
+90	O
+%	O
+at	O
+the	O
+aa	O
+and	O
+nt	O
+levels	O
+,	O
+respectively	O
+.	O
+
+In	O
+human	O
+brain	O
+,	O
+contactin	B-GENE
+was	O
+first	O
+identified	O
+by	O
+amino	O
+terminal	O
+and	O
+peptide	O
+sequencing	O
+of	O
+the	O
+lentil	B-GENE
+-	I-GENE
+lectin	I-GENE
+-	I-GENE
+binding	I-GENE
+glycoprotein	I-GENE
+Gp135	I-GENE
+.	O
+
+The	O
+centromeric	O
+YAC	O
+contig	O
+,	O
+which	O
+consists	O
+of	O
+23	O
+overlapping	O
+YACs	O
+and	O
+orders	O
+19	O
+sequence	O
+-	O
+tagged	O
+sites	O
+(	O
+STSs	O
+)	O
+,	O
+covers	O
+a	O
+minimum	O
+of	O
+2	O
+.	O
+2	O
+Mb	O
+and	O
+spans	O
+the	O
+Ewing	O
+sarcoma	O
+breakpoint	O
+.	O
+c	B-GENE
+-	I-GENE
+ets	I-GENE
+1	I-GENE
+and	O
+Fli	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+two	O
+members	O
+of	O
+the	O
+ets	B-GENE
+family	I-GENE
+,	O
+have	O
+been	O
+linked	O
+within	O
+400	O
+kb	O
+of	O
+intervening	O
+DNA	O
+within	O
+this	O
+contig	O
+,	O
+which	O
+also	O
+comprises	O
+a	O
+polymorphic	O
+microsatellite	O
+,	O
+D11S912	B-GENE
+(	O
+CA	O
+)	O
+n	O
+,	O
+which	O
+we	O
+have	O
+localized	O
+within	O
+the	O
+Fli	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+.	O
+
+A	O
+cDNA	O
+for	O
+a	O
+newly	O
+discovered	O
+pseudogene	O
+,	O
+closely	O
+related	O
+to	O
+the	O
+mouse	B-GENE
+mast	I-GENE
+cell	I-GENE
+chymases	I-GENE
+was	O
+isolated	O
+by	O
+polymerase	O
+chain	O
+reaction	O
+amplification	O
+from	O
+a	O
+mouse	O
+connective	O
+tissue	O
+-	O
+like	O
+mast	O
+cell	O
+line	O
+.	O
+
+IFI16	B-GENE
+consists	O
+of	O
+ten	O
+exons	O
+and	O
+nine	O
+intervening	O
+introns	O
+spanning	O
+at	O
+least	O
+28	O
+kilobases	O
+(	O
+kb	O
+)	O
+of	O
+DNA	O
+.	O
+
+Courses	O
+were	O
+repeated	O
+every	O
+four	O
+weeks	O
+.	O
+
+Peter	O
+Elfer	O
+explores	O
+the	O
+implications	O
+of	O
+the	O
+ruling	O
+.	O
+
+Other	O
+adverse	O
+events	O
+with	O
+incidences	O
+significantly	O
+higher	O
+than	O
+with	O
+placebo	O
+were	O
+dizziness	O
+,	O
+constipation	O
+,	O
+sweating	O
+,	O
+nervousness	O
+,	O
+and	O
+abnormal	O
+ejaculation	O
+.	O
+
+Homology	O
+was	O
+also	O
+detected	O
+between	O
+the	O
+putative	O
+transit	O
+peptide	O
+sequence	O
+of	O
+cysteine	B-GENE
+synthase	I-GENE
+C	I-GENE
+and	O
+other	O
+mitochondrion	O
+-	O
+targeting	O
+leader	O
+sequences	O
+.	O
+
+Furthermore	O
+,	O
+our	O
+data	O
+also	O
+show	O
+that	O
+,	O
+in	O
+addition	O
+to	O
+TEF	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+another	O
+HF	B-GENE
+-	I-GENE
+1a	I-GENE
+-	I-GENE
+related	I-GENE
+factor	I-GENE
+may	O
+be	O
+recognized	O
+by	O
+the	O
+alpha	B-GENE
+-	I-GENE
+MHC	I-GENE
+gene	I-GENE
+EM	O
+element	O
+.	O
+
+Rat	B-GENE
+kidney	I-GENE
+carboxylesterase	I-GENE
+.	O
+
+Recombinant	B-GENE
+I	I-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+inhibited	O
+kappa	B-GENE
+B	I-GENE
+motif	I-GENE
+binding	O
+by	O
+nuclear	B-GENE
+factor	I-GENE
+-	I-GENE
+kappa	I-GENE
+B1	I-GENE
+,	O
+RelA	B-GENE
+,	O
+and	O
+c	B-GENE
+-	I-GENE
+Rel	I-GENE
+as	O
+indicated	O
+by	O
+studies	O
+using	O
+UV	O
+radiation	O
+-	O
+induced	O
+covalent	O
+cross	O
+-	O
+linking	O
+to	O
+a	O
+bromodeoxyuridine	O
+-	O
+substituted	O
+kappa	B-GENE
+B	I-GENE
+oligonucleotide	I-GENE
+.	O
+
+The	O
+physical	O
+and	O
+chemical	O
+stability	O
+of	O
+a	O
+combination	O
+of	O
+drugs	O
+commonly	O
+administered	O
+into	O
+the	O
+epidural	O
+or	O
+intrathecal	O
+space	O
+for	O
+the	O
+treatment	O
+of	O
+chronic	O
+pain	O
+was	O
+investigated	O
+.	O
+
+Therefore	O
+,	O
+mechanisms	O
+that	O
+control	O
+activation	O
+of	O
+the	O
+MAP	B-GENE
+kinase	I-GENE
+cascade	O
+temporally	O
+and	O
+spatially	O
+may	O
+be	O
+important	O
+for	O
+specification	O
+of	O
+cellular	O
+responses	O
+.	O
+
+A	O
+candidate	O
+gene	O
+for	O
+Bcg	B-GENE
+,	O
+designated	O
+natural	B-GENE
+resistance	I-GENE
+-	I-GENE
+associated	I-GENE
+macrophage	I-GENE
+protein	I-GENE
+(	O
+Nramp	B-GENE
+)	O
+,	O
+has	O
+been	O
+isolated	O
+and	O
+shown	O
+to	O
+encode	O
+a	O
+novel	O
+macrophage	O
+-	O
+specific	O
+membrane	O
+protein	O
+,	O
+which	O
+is	O
+altered	O
+in	O
+susceptible	O
+animals	O
+.	O
+
+This	O
+motif	O
+is	O
+similar	O
+to	O
+but	O
+distinct	O
+from	O
+the	O
+LIM	B-GENE
+domain	I-GENE
+and	O
+the	O
+RING	B-GENE
+finger	I-GENE
+family	I-GENE
+,	O
+and	O
+is	O
+reminiscent	O
+of	O
+known	O
+metal	O
+-	O
+binding	O
+regions	O
+.	O
+
+The	O
+P131	O
+ORF	O
+is	O
+followed	O
+in	O
+-	O
+frame	O
+by	O
+a	O
+second	O
+ORF	O
+which	O
+is	O
+probably	O
+expressed	O
+by	O
+partial	O
+readthrough	O
+of	O
+the	O
+UGA	O
+termination	O
+codon	O
+of	O
+the	O
+P131	O
+ORF	O
+to	O
+produce	O
+a	O
+polypeptide	O
+of	O
+M	O
+(	O
+r	O
+)	O
+191044	O
+(	O
+P191	O
+)	O
+.	O
+
+One	O
+hundred	O
+fifty	O
+patients	O
+were	O
+reviewed	O
+at	O
+1	O
+year	O
+after	O
+arthroplasty	O
+.	O
+
+Elementary	O
+visual	O
+hallucinations	O
+in	O
+migraine	O
+and	O
+epilepsy	O
+.	O
+
+The	O
+influence	O
+of	O
+patient	O
+-	O
+related	O
+factors	O
+on	O
+inter	O
+-	O
+observer	O
+variability	O
+in	O
+the	O
+evaluation	O
+of	O
+neurological	O
+signs	O
+was	O
+investigated	O
+.	O
+
+The	O
+defined	O
+length	O
+of	O
+the	O
+mRNA	O
+,	O
+1	O
+,	O
+838	O
+nucleotides	O
+,	O
+was	O
+in	O
+agreement	O
+with	O
+that	O
+of	O
+a	O
+1	O
+.	O
+9	O
+-	O
+kb	O
+RNA	O
+expressed	O
+throughout	O
+the	O
+replication	O
+cycle	O
+,	O
+starting	O
+at	O
+the	O
+early	O
+stages	O
+of	O
+infection	O
+.	O
+
+Infect	O
+.	O
+
+Transient	O
+transfections	O
+of	O
+a	O
+construct	O
+expressing	O
+the	O
+RNA	O
+transcript	O
+defined	O
+by	O
+clone	O
+B1	O
+.	O
+1	O
+into	O
+D17	O
+cells	O
+led	O
+to	O
+the	O
+expression	O
+of	O
+an	O
+Env	B-GENE
+/	O
+Mlvi	B-GENE
+-	I-GENE
+4	I-GENE
+fusion	O
+protein	O
+with	O
+an	O
+apparent	O
+molecular	O
+mass	O
+of	O
+33	O
+kDa	O
+.	O
+
+Roizman	O
+,	O
+J	O
+.	O
+
+Articles	O
+addressing	O
+valvular	O
+heart	O
+disease	O
+or	O
+heart	O
+failure	O
+secondary	O
+to	O
+acute	O
+myocardial	O
+infarction	O
+or	O
+Chagas	O
+'	O
+disease	O
+were	O
+excluded	O
+.	O
+
+All	O
+nuclear	O
+receptors	O
+have	O
+several	O
+well	O
+-	O
+characterized	O
+structural	O
+domains	O
+,	O
+including	O
+a	O
+conserved	O
+DNA	O
+-	O
+binding	O
+domain	O
+,	O
+and	O
+a	O
+ligand	O
+binding	O
+domain	O
+at	O
+the	O
+carboxyl	O
+terminus	O
+of	O
+the	O
+receptor	O
+.	O
+
+The	O
+sample	O
+includes	O
+all	O
+the	O
+HIV	O
+-	O
+infected	O
+-	O
+patients	O
+continuously	O
+referred	O
+to	O
+the	O
+Outpatient	O
+Service	O
+of	O
+the	O
+Infectious	O
+Diseases	O
+dept	O
+.	O
+of	O
+Bologna	O
+'	O
+s	O
+"	O
+Ospedale	O
+Maggiore	O
+"	O
+General	O
+Hospital	O
+during	O
+some	O
+five	O
+days	O
+(	O
+19	O
+-	O
+23rd	O
+,	O
+July	O
+1993	O
+)	O
+.	O
+
+Using	O
+in	O
+organello	O
+footprint	O
+analysis	O
+,	O
+we	O
+demonstrate	O
+that	O
+within	O
+human	O
+placental	O
+mitochondria	O
+there	O
+is	O
+a	O
+high	O
+level	O
+of	O
+protein	O
+-	O
+DNA	O
+binding	O
+at	O
+regularly	O
+phased	O
+intervals	O
+throughout	O
+a	O
+500	O
+-	O
+bp	O
+region	O
+encompassing	O
+the	O
+D	O
+-	O
+loop	O
+DNA	O
+origins	O
+and	O
+two	O
+promoter	O
+regions	O
+.	O
+
+The	O
+Nur77	B-GENE
+protein	I-GENE
+can	O
+act	O
+as	O
+a	O
+potent	O
+transcription	O
+activator	O
+and	O
+may	O
+function	O
+to	O
+regulate	O
+the	O
+expression	O
+of	O
+downstream	O
+genes	O
+in	O
+response	O
+to	O
+extracellular	O
+stimuli	O
+.	O
+
+One	O
+class	O
+of	O
+plasmids	O
+contained	O
+tRNA	B-GENE
+(	I-GENE
+His	I-GENE
+)	I-GENE
+genes	I-GENE
+and	O
+conferred	O
+efficient	O
+suppression	O
+only	O
+when	O
+cells	O
+were	O
+starved	O
+for	O
+histidine	O
+;	O
+these	O
+plasmids	O
+suppressed	O
+a	O
+gcn2	B-GENE
+deletion	O
+much	O
+less	O
+efficiently	O
+than	O
+they	O
+suppressed	O
+gcn2	B-GENE
+-	I-GENE
+507	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+presence	O
+of	O
+the	O
+Cln2	B-GENE
+PEST	I-GENE
+domain	I-GENE
+was	O
+sufficient	O
+to	O
+destabilize	O
+a	O
+heterologous	O
+protein	O
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+with	O
+each	O
+of	O
+these	O
+sequences	O
+demonstrated	O
+complexes	O
+with	O
+mobilities	O
+identical	O
+to	O
+those	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+site	I-GENE
+from	O
+the	O
+kappa	B-GENE
+light	I-GENE
+-	I-GENE
+chain	I-GENE
+gene	I-GENE
+.	O
+
+Although	O
+a	O
+carboxyl	O
+-	O
+terminal	O
+HSF	B-GENE
+transcriptional	O
+activation	O
+domain	O
+is	O
+critical	O
+for	O
+the	O
+activation	O
+of	O
+CUP1	B-GENE
+transcription	O
+in	O
+response	O
+to	O
+both	O
+heat	O
+shock	O
+stress	O
+and	O
+glucose	O
+starvation	O
+,	O
+this	O
+region	O
+is	O
+dispensable	O
+for	O
+transient	O
+heat	O
+shock	O
+activation	O
+of	O
+at	O
+least	O
+two	O
+genes	O
+encoding	O
+members	O
+of	O
+the	O
+S	O
+.	O
+cerevisiae	O
+hsp70	B-GENE
+family	I-GENE
+.	O
+
+We	O
+have	O
+recently	O
+detected	O
+high	O
+levels	O
+of	O
+CKB	B-GENE
+mRNA	I-GENE
+in	O
+HeLa	O
+cells	O
+and	O
+,	O
+in	O
+this	O
+study	O
+,	O
+have	O
+tested	O
+whether	O
+this	O
+may	O
+be	O
+due	O
+to	O
+the	O
+extremely	O
+low	O
+amounts	O
+of	O
+p53	B-GENE
+protein	I-GENE
+present	O
+in	O
+HeLa	O
+cells	O
+.	O
+
+Distal	O
+lower	O
+motor	O
+neuron	O
+syndrome	O
+with	O
+high	O
+-	O
+titer	O
+serum	B-GENE
+IgM	I-GENE
+anti	I-GENE
+-	I-GENE
+GM1	I-GENE
+antibodies	I-GENE
+:	O
+improvement	O
+following	O
+immunotherapy	O
+with	O
+monthly	O
+plasma	O
+exchange	O
+and	O
+intravenous	O
+cyclophosphamide	O
+.	O
+
+Regulators	O
+responsible	O
+for	O
+the	O
+pervasive	O
+,	O
+nonsex	O
+-	O
+specific	O
+alternative	O
+pre	O
+-	O
+mRNA	O
+splicing	O
+characteristic	O
+of	O
+metazoans	O
+are	O
+almost	O
+entirely	O
+unknown	O
+or	O
+uncertain	O
+.	O
+
+A	O
+normal	O
+systemic	O
+response	O
+was	O
+obtained	O
+after	O
+IF	O
+,	O
+indicating	O
+that	O
+rhG	B-GENE
+-	I-GENE
+CSF	I-GENE
+retains	O
+activity	O
+in	O
+the	O
+solid	O
+state	O
+.	O
+
+PAI	B-GENE
+-	I-GENE
+1	I-GENE
+levels	O
+increased	O
+significantly	O
+in	O
+patients	O
+who	O
+received	O
+iohexol	O
+but	O
+not	O
+in	O
+those	O
+who	O
+received	O
+ioxaglate	O
+.	O
+
+Determination	O
+of	O
+potassium	O
+iodide	O
+in	O
+Polish	O
+edible	O
+salt	O
+
+The	O
+recovery	O
+value	O
+of	O
+systolic	O
+pressure	O
+was	O
+higher	O
+than	O
+diastolic	O
+pressure	O
+and	O
+pulse	O
+pressure	O
+increased	O
+.	O
+
+The	O
+importance	O
+of	O
+hepatitis	O
+C	O
+virus	O
+(	O
+HCV	O
+)	O
+infection	O
+as	O
+a	O
+cause	O
+of	O
+chronic	O
+liver	O
+disease	O
+has	O
+become	O
+clear	O
+with	O
+the	O
+introduction	O
+of	O
+serologic	O
+detection	O
+methods	O
+.	O
+
+Human	O
+adenovirus	O
+type	O
+41	O
+contains	O
+two	O
+fibers	O
+.	O
+
+Outflow	O
+obstruction	O
+of	O
+pancreatic	O
+juice	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+"	O
+relative	O
+stenosis	O
+of	O
+the	O
+minor	O
+papilla	O
+,	O
+"	O
+was	O
+considered	O
+to	O
+be	O
+present	O
+in	O
+the	O
+patients	O
+with	O
+type	O
+II	O
+papilla	O
+,	O
+and	O
+,	O
+therefore	O
+,	O
+the	O
+patients	O
+with	O
+type	O
+II	O
+papilla	O
+might	O
+suffer	O
+from	O
+acute	O
+pancreatitis	O
+resulting	O
+from	O
+poor	O
+drainage	O
+of	O
+pancreatic	O
+juice	O
+and	O
+excessive	O
+pressure	O
+in	O
+the	O
+dorsal	O
+duct	O
+.	O
+
+Sequencing	O
+of	O
+the	O
+TP53	B-GENE
+transcripts	I-GENE
+from	O
+exons	O
+2	O
+to	O
+10	O
+,	O
+however	O
+,	O
+did	O
+not	O
+reveal	O
+mutations	O
+of	O
+the	O
+remaining	O
+allele	O
+in	O
+any	O
+of	O
+these	O
+tumors	O
+.	O
+
+An	O
+unusual	O
+complication	O
+in	O
+an	O
+unsuitable	O
+patient	O
+.	O
+
+In	O
+the	O
+ISO	O
+group	O
+,	O
+at	O
+pre	O
+-	O
+DEX	O
+,	O
+CBF	O
+increased	O
+from	O
+86	O
++	O
+/	O
+-	O
+8	O
+to	O
+166	O
++	O
+/	O
+-	O
+19	O
+mL	O
+.	O
+min	O
+-	O
+1	O
+.	O
+100	O
+g	O
+-	O
+1	O
+in	O
+response	O
+to	O
+hypercapnia	O
+(	O
+PCO2	O
+approximately	O
+90	O
+mmHg	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+All	O
+other	O
+ejaculate	O
+parameters	O
+(	O
+density	O
+,	O
+motility	O
+,	O
+swelling	O
+test	O
+,	O
+penetration	O
+test	O
+)	O
+remained	O
+unchanged	O
+,	O
+and	O
+there	O
+was	O
+only	O
+one	O
+post	O
+-	O
+therapeutic	O
+pregnancy	O
+.	O
+
+KRN2391	O
+and	O
+cromakalim	O
+produced	O
+a	O
+dose	O
+-	O
+dependent	O
+increase	O
+in	O
+aortic	O
+and	O
+coronary	O
+blood	O
+flow	O
+.	O
+
+In	O
+H4IIE	O
+rat	O
+hepatoma	O
+cells	O
+,	O
+glucocorticoids	O
+,	O
+retinoic	O
+acid	O
+and	O
+cyclic	O
+AMP	O
+(	O
+cAMP	O
+)	O
+increase	O
+PEPCK	B-GENE
+gene	I-GENE
+transcription	O
+whereas	O
+insulin	B-GENE
+and	O
+phorbol	O
+esters	O
+have	O
+the	O
+opposite	O
+effect	O
+.	O
+
+Acta	O
+572	O
+,	O
+113	O
+-	O
+120	O
+]	O
+.	O
+
+Basal	O
+plasma	O
+AVP	B-GENE
+levels	O
+and	O
+AVP	B-GENE
+release	O
+after	O
+postural	O
+change	O
+were	O
+assessed	O
+,	O
+and	O
+plasma	O
+NPY	B-GENE
+levels	O
+were	O
+measured	O
+in	O
+the	O
+same	O
+samples	O
+.	O
+
+A	O
+stretch	O
+of	O
+16	O
+nucleotides	O
+just	O
+upstream	O
+of	O
+the	O
+IL	B-GENE
+-	I-GENE
+4RE	I-GENE
+contributed	O
+to	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+inducibility	O
+and	O
+formed	O
+nucleoprotein	O
+complexes	O
+with	O
+constitutive	O
+factors	O
+.	O
+
+Our	O
+previous	O
+study	O
+suggested	O
+that	O
+pertussis	B-GENE
+toxin	I-GENE
+(	O
+IAP	B-GENE
+)	O
+-	O
+sensitive	O
+GTP	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	I-GENE
+s	I-GENE
+)	I-GENE
+(	O
+G	B-GENE
+-	I-GENE
+protein	I-GENE
+)	O
+is	O
+involved	O
+in	O
+the	O
+process	O
+of	O
+differentiation	O
+by	O
+hormones	O
+/	O
+IBMX	O
+,	O
+accompanied	O
+by	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+induction	O
+.	O
+
+ATX	B-GENE
+,	O
+like	O
+PC	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+was	O
+found	O
+to	O
+hydrolyze	O
+the	O
+type	B-GENE
+I	I-GENE
+phosphodiesterase	I-GENE
+substrate	O
+p	O
+-	O
+nitrophenyl	O
+thymidine	O
+-	O
+5	O
+'	O
+-	O
+monophosphate	O
+.	O
+
+The	O
+effect	O
+of	O
+site	O
+-	O
+specific	O
+mutations	O
+in	O
+the	O
+mouse	B-GENE
+platelet	I-GENE
+-	I-GENE
+derived	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	I-GENE
+PDGF	I-GENE
+)	I-GENE
+beta	I-GENE
+-	I-GENE
+receptor	I-GENE
+on	O
+activation	O
+of	O
+the	O
+Na	B-GENE
++	I-GENE
+/	I-GENE
+H	I-GENE
++	I-GENE
+exchanger	I-GENE
+was	O
+examined	O
+in	O
+normal	O
+murine	O
+mammary	O
+gland	O
+epithelial	O
+(	O
+NMuMG	O
+)	O
+and	O
+Chinese	O
+hamster	O
+ovary	O
+(	O
+CHO	O
+)	O
+cells	O
+.	O
+
+Sequence	O
+analysis	O
+revealed	O
+:	O
+1	O
+)	O
+a	O
+kinase	O
+catalytic	O
+domain	O
+most	O
+characteristic	O
+of	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+kinases	I-GENE
+but	O
+hybrid	O
+between	O
+members	O
+of	O
+the	O
+family	O
+of	O
+microtubule	B-GENE
+-	I-GENE
+associated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+kinases	I-GENE
+and	O
+the	O
+fibroblast	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+family	I-GENE
+;	O
+2	O
+)	O
+two	O
+putative	O
+alpha	O
+-	O
+helical	O
+leucine	O
+zipper	O
+motifs	O
+separated	O
+by	O
+a	O
+25	O
+-	O
+amino	O
+acid	O
+charged	O
+intermediate	O
+segment	O
+but	O
+lacking	O
+an	O
+NH2	O
+-	O
+terminal	O
+basic	O
+domain	O
+;	O
+and	O
+3	O
+)	O
+COOH	O
+-	O
+terminal	O
+and	O
+NH2	O
+-	O
+terminal	O
+proline	O
+-	O
+rich	O
+domains	O
+suggestive	O
+of	O
+src	B-GENE
+homology	I-GENE
+3	I-GENE
+(	O
+SH3	B-GENE
+)	O
+domain	O
+binding	O
+regions	O
+.	O
+
+Type	O
+2	O
+genomes	O
+containing	O
+this	O
+sequence	O
+presumably	O
+more	O
+closely	O
+reflect	O
+the	O
+structure	O
+of	O
+the	O
+infectious	O
+,	O
+replication	O
+-	O
+competent	O
+retrovirus	O
+ancestors	O
+of	O
+the	O
+HERV	O
+-	O
+K	O
+family	O
+than	O
+do	O
+type	O
+1	O
+genomes	O
+that	O
+lack	O
+the	O
+sequence	O
+.	O
+
+However	O
+,	O
+when	O
+domain	O
+I	O
+and	O
+domain	O
+II	O
+were	O
+linked	O
+on	O
+the	O
+same	O
+plasmid	O
+,	O
+high	O
+levels	O
+of	O
+replication	O
+were	O
+observed	O
+.	O
+
+Point	O
+mutations	O
+that	O
+suppressed	O
+the	O
+in	O
+vitro	O
+binding	O
+of	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+to	O
+the	O
+internal	O
+palindromic	O
+arm	O
+reduced	O
+the	O
+activity	O
+of	O
+the	O
+resident	O
+P4	O
+promoter	O
+,	O
+while	O
+those	O
+preventing	O
+complex	O
+formation	O
+with	O
+USF	B-GENE
+did	O
+not	O
+,	O
+as	O
+determined	O
+by	O
+transient	O
+expression	O
+assays	O
+using	O
+the	O
+luciferase	B-GENE
+reporter	O
+gene	O
+.	O
+
+Surprisingly	O
+,	O
+nuclear	O
+forms	O
+of	O
+IE110	B-GENE
+were	O
+found	O
+to	O
+move	O
+a	O
+cytoplasmic	O
+form	O
+of	O
+IE175	B-GENE
+into	O
+nuclear	O
+punctate	O
+structures	O
+,	O
+and	O
+a	O
+cytoplasmic	O
+form	O
+of	O
+IE110	B-GENE
+was	O
+able	O
+to	O
+retain	O
+nuclear	O
+forms	O
+of	O
+IE175	B-GENE
+in	O
+cytoplasmic	O
+punctate	O
+structures	O
+.	O
+
+Transcription	O
+of	O
+the	O
+gene	O
+for	O
+ivanolysin	B-GENE
+O	I-GENE
+and	O
+expression	O
+of	O
+other	O
+genes	O
+of	O
+the	O
+virulence	B-GENE
+gene	I-GENE
+cluster	I-GENE
+in	I-GENE
+L	I-GENE
+.	I-GENE
+ivanovii	I-GENE
+were	O
+dependent	O
+on	O
+PrfA	B-GENE
+.	O
+
+Moreover	O
+,	O
+by	O
+complementation	O
+of	O
+the	O
+WA	B-GENE
+fyuA	I-GENE
+mutant	I-GENE
+by	O
+the	O
+cloned	O
+fyuA	B-GENE
+gene	I-GENE
+,	O
+yersiniabactin	O
+uptake	O
+and	O
+mouse	O
+virulence	O
+were	O
+restored	O
+.	O
+
+The	O
+ICBF	O
+in	O
+the	O
+ischaemic	O
+cortex	O
+revealed	O
+a	O
+graded	O
+reduction	O
+from	O
+the	O
+ischaemic	O
+centre	O
+to	O
+the	O
+surrounding	O
+tissues	O
+.	O
+
+The	O
+treatment	O
+of	O
+hydronephrosis	O
+in	O
+children	O
+
+The	O
+inflation	O
+hub	O
+of	O
+the	O
+probe	O
+is	O
+recreated	O
+by	O
+modifying	O
+a	O
+standard	O
+USCI	O
+Tuohy	O
+-	O
+Borst	O
+Y	O
+adaptor	O
+and	O
+attaching	O
+this	O
+to	O
+the	O
+transected	O
+probe	O
+hypotube	O
+.	O
+
+The	O
+other	O
+element	O
+bound	O
+RBP	B-GENE
+-	I-GENE
+J	I-GENE
+kappa	I-GENE
+with	O
+low	O
+affinity	O
+.	O
+
+The	O
+basal	O
+promoter	O
+strength	O
+of	O
+constructs	O
+that	O
+contained	O
+deletions	O
+in	O
+the	O
+U5	B-GENE
+region	I-GENE
+of	O
+the	O
+LTR	O
+was	O
+analyzed	O
+by	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+assays	O
+following	O
+transfection	O
+of	O
+HeLa	O
+cells	O
+or	O
+Jurkat	O
+T	O
+-	O
+cells	O
+in	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+viral	O
+transactivator	O
+tax	B-GENE
+protein	O
+.	O
+
+In	O
+reviewing	O
+a	O
+number	O
+of	O
+the	O
+most	O
+intensely	O
+studied	O
+environmentally	O
+inducible	O
+promoters	O
+it	O
+becomes	O
+clear	O
+that	O
+the	O
+presence	O
+of	O
+two	O
+cis	O
+-	O
+acting	O
+elements	O
+are	O
+critical	O
+for	O
+promoter	O
+activity	O
+,	O
+one	O
+of	O
+which	O
+is	O
+the	O
+G	O
+-	O
+box	O
+(	O
+CCACGTGG	O
+)	O
+.	O
+
+Recently	O
+,	O
+a	O
+protein	O
+designated	O
+GF14	B-GENE
+has	O
+been	O
+isolated	O
+that	O
+is	O
+associated	O
+with	O
+the	O
+GBF	B-GENE
+protein	I-GENE
+complex	I-GENE
+.	O
+
+New	O
+diagnostic	O
+strategies	O
+for	O
+lupus	O
+anticoagulants	O
+and	O
+antiphospholipid	O
+antibodies	O
+.	O
+
+Propafenone	O
+is	O
+well	O
+tolerated	O
+in	O
+the	O
+majority	O
+of	O
+young	O
+patients	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+yeast	B-GENE
+CEG1	I-GENE
+demonstrated	O
+that	O
+four	O
+of	O
+the	O
+five	O
+conserved	O
+motifs	O
+are	O
+essential	O
+for	O
+capping	B-GENE
+enzyme	I-GENE
+function	O
+in	O
+vivo	O
+.	O
+
+2	O
+patients	O
+(	O
+11	O
+%	O
+)	O
+had	O
+significant	O
+morbidity	O
+502	O
+and	O
+529	O
+days	O
+respectively	O
+after	O
+transplantation	O
+.	O
+
+Alternative	O
+splicing	O
+of	O
+the	O
+cytoplasmic	O
+tail	O
+appears	O
+to	O
+generate	O
+multiple	O
+PECAM	B-GENE
+-	I-GENE
+1	I-GENE
+isoforms	I-GENE
+that	O
+may	O
+regulate	O
+phosphorylation	O
+,	O
+cytoskeletal	O
+association	O
+,	O
+and	O
+affinity	O
+modulation	O
+of	O
+the	O
+mature	O
+protein	O
+.	O
+
+Transfer	O
+also	O
+correlated	O
+inversely	O
+with	O
+gastric	O
+juice	O
+pH	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+619	O
+,	O
+P	O
+<	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+This	O
+technique	O
+has	O
+a	O
+sensitivity	O
+and	O
+a	O
+specificity	O
+of	O
+almost	O
+100	O
+%	O
+,	O
+and	O
+is	O
+currently	O
+the	O
+best	O
+way	O
+to	O
+diagnose	O
+nodal	O
+involvement	O
+,	O
+apart	O
+from	O
+laparotomy	O
+.	O
+
+The	O
+data	O
+show	O
+conclusively	O
+that	O
+phosphorylation	O
+of	O
+His	O
+-	O
+304	O
+is	O
+not	O
+essential	O
+for	O
+any	O
+of	O
+the	O
+known	O
+functions	O
+of	O
+A	B-GENE
+.	I-GENE
+vinelandii	I-GENE
+NifL	I-GENE
+.	O
+
+If	O
+this	O
+is	O
+present	O
+,	O
+such	O
+patients	O
+should	O
+be	O
+closely	O
+monitored	O
+,	O
+and	O
+any	O
+atypical	O
+lesions	O
+biopsied	O
+.	O
+
+Cumulated	O
+maximum	O
+lod	O
+scores	O
+between	O
+FRDA	B-GENE
+and	O
+D9S5	B-GENE
+and	O
+between	O
+FRDA	B-GENE
+and	O
+D9S15	B-GENE
+are	O
+above	O
+36	O
+and	O
+61	O
+,	O
+respectively	O
+,	O
+at	O
+a	O
+recombination	O
+fraction	O
+of	O
+0	O
+,	O
+indicating	O
+that	O
+recombination	O
+events	O
+needed	O
+to	O
+orient	O
+the	O
+search	O
+of	O
+the	O
+gene	O
+are	O
+very	O
+difficult	O
+to	O
+identify	O
+and	O
+ascertain	O
+.	O
+
+A	O
+receptor	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+kinase	I-GENE
+,	O
+OsPK10	B-GENE
+,	O
+has	O
+been	O
+cloned	O
+from	O
+rice	O
+(	O
+Oryza	O
+sativa	O
+)	O
+.	O
+
+A	O
+sequence	O
+representing	O
+about	O
+50	O
+%	O
+of	O
+the	O
+expected	O
+complete	O
+sequence	O
+was	O
+obtained	O
+by	O
+translation	O
+of	O
+the	O
+two	O
+open	O
+reading	O
+frames	O
+present	O
+on	O
+a	O
+1	O
+.	O
+6	O
+kb	O
+DNA	O
+genomic	O
+fragment	O
+.	O
+
+Goodpasture	O
+'	O
+s	O
+-	O
+like	O
+syndrome	O
+and	O
+effect	O
+of	O
+extracorporeal	O
+membrane	O
+oxygenator	O
+support	O
+.	O
+
+A	O
+cDNA	O
+clone	O
+pCZ1	O
+,	O
+with	O
+a	O
+1	O
+.	O
+1	O
+kb	O
+insert	O
+,	O
+was	O
+isolated	O
+from	O
+a	O
+NaCl	O
+-	O
+adapted	O
+tobacco	O
+cell	O
+cDNA	O
+library	O
+that	O
+encodes	O
+an	O
+apparently	O
+full	O
+-	O
+length	O
+29	O
+kDa	O
+protein	O
+(	O
+251	O
+amino	O
+acids	O
+)	O
+with	O
+a	O
+calculated	O
+pI	O
+of	O
+5	O
+.	O
+7	O
+.	O
+
+METHODS	O
+-	O
+-	O
+16	O
+volunteered	O
+for	O
+spirometry	O
+with	O
+methacholine	O
+provocation	O
+test	O
+including	O
+a	O
+test	O
+for	O
+small	O
+airways	O
+function	O
+by	O
+volume	O
+of	O
+trapped	O
+gas	O
+(	O
+VTG	O
+)	O
+.	O
+
+Relationship	O
+of	O
+CDK	B-GENE
+-	I-GENE
+activating	I-GENE
+kinase	I-GENE
+and	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+CTD	O
+kinase	O
+TFIIH	B-GENE
+/	O
+TFIIK	B-GENE
+.	O
+
+These	O
+same	O
+regions	O
+showed	O
+remarkable	O
+homology	O
+to	O
+two	O
+invertebrate	O
+proteins	O
+,	O
+CNC	B-GENE
+and	O
+skin	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+postulated	O
+to	O
+regulate	O
+embryonic	O
+development	O
+in	O
+Drosophila	O
+melanogaster	O
+and	O
+Caenorhabditis	O
+elegans	O
+,	O
+respectively	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+has	O
+confirmed	O
+that	O
+this	O
+mutation	O
+affects	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+alpha	O
+subunit	O
+,	O
+changing	O
+a	O
+leucine	O
+residue	O
+at	O
+position	O
+290	O
+to	O
+a	O
+histidine	O
+(	O
+rpoAL290H	B-GENE
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+findings	O
+indicate	O
+a	O
+physical	O
+barrier	O
+of	O
+oesophageal	O
+surfactant	O
+which	O
+could	O
+offer	O
+some	O
+degree	O
+of	O
+protection	O
+against	O
+gastro	O
+-	O
+oesophageal	O
+reflux	O
+but	O
+one	O
+which	O
+is	O
+particularly	O
+prone	O
+to	O
+attack	O
+by	O
+bile	O
+.	O
+
+Differential	O
+screening	O
+of	O
+mitochondrial	O
+cDNA	O
+libraries	O
+from	O
+male	O
+-	O
+fertile	O
+and	O
+cytoplasmic	O
+male	O
+-	O
+sterile	O
+sugar	O
+-	O
+beet	O
+reveals	O
+genome	O
+rearrangements	O
+at	O
+atp6	B-GENE
+and	O
+atpA	B-GENE
+loci	I-GENE
+.	O
+
+The	O
+effects	O
+of	O
+social	O
+isolation	O
+on	O
+morphine	O
+-	O
+induced	O
+locomotor	O
+activity	O
+were	O
+compared	O
+in	O
+:	O
+(	O
+i	O
+)	O
+animals	O
+with	O
+an	O
+intact	O
+hypothalamo	O
+-	O
+pituitary	O
+-	O
+adrenal	O
+(	O
+HPA	O
+)	O
+axis	O
+;	O
+(	O
+ii	O
+)	O
+animals	O
+in	O
+which	O
+stress	O
+-	O
+induced	O
+corticosterone	O
+secretion	O
+was	O
+blocked	O
+by	O
+adrenalectomy	O
+.	O
+
+Using	O
+this	O
+reporter	O
+gene	O
+system	O
+,	O
+we	O
+previously	O
+showed	O
+that	O
+EPO	B-GENE
+-	O
+induced	O
+activation	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+promoter	I-GENE
+can	O
+be	O
+detected	O
+rapidly	O
+and	O
+sensitively	O
+as	O
+an	O
+elevation	O
+of	O
+cellular	B-GENE
+luciferase	I-GENE
+activity	O
+.	O
+
+I	O
+hypothesize	O
+that	O
+white	B-GENE
+gene	I-GENE
+expression	O
+from	O
+P	B-GENE
+[	I-GENE
+en	I-GENE
+]	I-GENE
+is	O
+repressed	O
+by	O
+the	O
+formation	O
+of	O
+a	O
+protein	O
+complex	O
+which	O
+is	O
+initiated	O
+at	O
+the	O
+engrailed	B-GENE
+PS	I-GENE
+sites	I-GENE
+and	O
+also	O
+requires	O
+interactions	O
+with	O
+flanking	O
+genomic	O
+DNA	O
+.	O
+
+SPP41	B-GENE
+was	O
+cloned	O
+and	O
+sequenced	O
+and	O
+found	O
+to	O
+be	O
+essential	O
+.	O
+spp43	B-GENE
+is	O
+allelic	O
+to	O
+the	O
+previously	O
+identified	O
+suppressor	B-GENE
+srn1	I-GENE
+,	O
+which	O
+encodes	O
+a	O
+negative	O
+regulator	O
+of	O
+gene	O
+expression	O
+.	O
+
+Standard	O
+curve	O
+correlation	O
+coefficients	O
+of	O
+0	O
+.	O
+995	O
+or	O
+greater	O
+were	O
+obtained	O
+during	O
+validation	O
+experiments	O
+and	O
+analysis	O
+of	O
+study	O
+samples	O
+.	O
+
+To	O
+see	O
+if	O
+a	O
+pulse	O
+oximeter	O
+can	O
+monitor	O
+the	O
+fetus	O
+during	O
+labour	O
+we	O
+recruited	O
+100	O
+Caucasian	O
+women	O
+in	O
+normal	O
+uncomplicated	O
+labour	O
+.	O
+
+There	O
+was	O
+no	O
+difference	O
+in	O
+plasma	O
+concentrations	O
+of	O
+PGI2	O
+(	O
+figure	O
+4	O
+)	O
+and	O
+TxA2	O
+in	O
+patients	O
+with	O
+normal	O
+blood	O
+pressure	O
+,	O
+mild	O
+preeclampsia	O
+and	O
+hypotension	O
+,	O
+whereas	O
+in	O
+severe	O
+preeclampsia	O
+,	O
+the	O
+plasma	O
+concentration	O
+of	O
+PGI2	O
+was	O
+significantly	O
+lower	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+of	O
+TxA2	O
+significantly	O
+higher	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+A	O
+causal	O
+analysis	O
+of	O
+secondary	O
+variables	O
+showed	O
+that	O
+the	O
+formation	O
+of	O
+FB	O
+memories	O
+was	O
+primarily	O
+associated	O
+with	O
+the	O
+level	O
+of	O
+importance	O
+attached	O
+to	O
+the	O
+event	O
+and	O
+level	O
+of	O
+affective	O
+response	O
+to	O
+the	O
+news	O
+.	O
+
+The	O
+IPL1	B-GENE
+gene	I-GENE
+is	O
+required	O
+for	O
+high	O
+-	O
+fidelity	O
+chromosome	O
+segregation	O
+in	O
+the	O
+budding	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+2	O
+.	O
+
+The	O
+complete	O
+gene	O
+organization	O
+was	O
+obtained	O
+by	O
+combining	O
+the	O
+results	O
+of	O
+the	O
+sequence	O
+of	O
+these	O
+clones	O
+and	O
+those	O
+of	O
+the	O
+characterization	O
+of	O
+polymerase	O
+chain	O
+reaction	O
+-	O
+amplified	O
+genomic	O
+segments	O
+.	O
+
+INO2	B-GENE
+,	O
+a	O
+regulatory	O
+gene	O
+in	O
+yeast	O
+phospholipid	O
+biosynthesis	O
+,	O
+affects	O
+nuclear	O
+segregation	O
+and	O
+bud	O
+pattern	O
+formation	O
+.	O
+
+The	O
+pentafluorobenzyl	O
+derivative	O
+of	O
+clonidine	O
+yields	O
+an	O
+intense	O
+ion	O
+fragment	O
+at	O
+m	O
+/	O
+z	O
+354	O
+,	O
+and	O
+the	O
+lower	O
+limit	O
+of	O
+detection	O
+is	O
+0	O
+.	O
+025	O
+ng	O
+/	O
+ml	O
+for	O
+a	O
+1	O
+-	O
+ml	O
+plasma	O
+sample	O
+.	O
+
+Mammalian	B-GENE
+ABPs	I-GENE
+and	O
+SHBGs	B-GENE
+bind	O
+sex	O
+steroids	O
+with	O
+high	O
+affinity	O
+,	O
+but	O
+some	O
+binding	O
+properties	O
+differ	O
+among	O
+species	O
+.	O
+
+Src	B-GENE
+homology	I-GENE
+(	O
+SH	B-GENE
+)	O
+domain	O
+dependent	O
+protein	O
+-	O
+protein	O
+interactions	O
+are	O
+important	O
+to	O
+tyrosine	B-GENE
+kinase	I-GENE
+receptor	I-GENE
+signal	O
+transduction	O
+.	O
+
+Sample	O
+treatment	O
+was	O
+optimized	O
+in	O
+order	O
+to	O
+achieve	O
+a	O
+complete	O
+extraction	O
+of	O
+labetalol	O
+diastereoisomers	O
+and	O
+to	O
+avoid	O
+racemization	O
+during	O
+extraction	O
+.	O
+
+Under	O
+resting	O
+conditions	O
+,	O
+activity	O
+levels	O
+of	O
+cardiac	O
+vagal	O
+and	O
+sympathetic	O
+outflows	O
+are	O
+not	O
+related	O
+across	O
+young	O
+,	O
+healthy	O
+human	O
+subjects	O
+and	O
+peripheral	O
+interaction	O
+is	O
+not	O
+manifest	O
+between	O
+the	O
+autonomic	O
+divisions	O
+.	O
+
+Both	O
+proprioceptive	O
+and	O
+electroreceptive	O
+units	O
+showed	O
+a	O
+progression	O
+of	O
+receptive	O
+fields	O
+from	O
+anterior	O
+to	O
+posterior	O
+body	O
+in	O
+the	O
+rostral	O
+to	O
+caudal	O
+direction	O
+along	O
+the	O
+length	O
+of	O
+DGR	O
+.	O
+
+In	O
+control	O
+patients	O
+,	O
+baseline	O
+images	O
+presented	O
+Type	O
+I	O
+in	O
+25	O
+,	O
+Type	O
+II	O
+in	O
+7	O
+,	O
+and	O
+the	O
+Type	O
+III	O
+&	O
+IV	O
+in	O
+0	O
+,	O
+and	O
+the	O
+Type	O
+after	O
+loading	O
+was	O
+the	O
+same	O
+as	O
+the	O
+Type	O
+at	O
+baseline	O
+.	O
+
+A	O
+more	O
+complete	O
+analysis	O
+of	O
+dose	O
+response	O
+,	O
+time	O
+and	O
+mode	O
+of	O
+Ga	O
+administration	O
+(	O
+preinjury	O
+or	O
+postinjury	O
+)	O
+,	O
+and	O
+availability	O
+of	O
+Ga	O
+across	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+is	O
+needed	O
+to	O
+further	O
+evaluate	O
+the	O
+efficacy	O
+of	O
+this	O
+compound	O
+.	O
+
+The	O
+presence	O
+of	O
+regulatory	O
+sequences	O
+for	O
+the	O
+binding	O
+of	O
+transcription	O
+factors	O
+such	O
+as	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+whose	O
+activation	O
+is	O
+associated	O
+with	O
+the	O
+immediate	O
+response	O
+of	O
+the	O
+cell	O
+to	O
+an	O
+injury	O
+,	O
+may	O
+be	O
+an	O
+indication	O
+of	O
+the	O
+important	O
+role	O
+which	O
+HO	B-GENE
+-	I-GENE
+1	I-GENE
+may	O
+play	O
+in	O
+defense	O
+mechanisms	O
+against	O
+tissue	O
+injury	O
+.	O
+
+Granisetron	O
+,	O
+but	O
+not	O
+saline	O
+,	O
+abolished	O
+vomiting	O
+and	O
+nausea	O
+when	O
+given	O
+as	O
+intervention	O
+after	O
+this	O
+combined	O
+emetic	O
+regimen	O
+.	O
+
+The	O
+femoroarterial	O
+coronary	O
+sinus	O
+difference	O
+in	O
+lactate	O
+turned	O
+negative	O
+,	O
+and	O
+pH	O
+,	O
+PCO2	O
+and	O
+potassium	O
+differences	O
+increased	O
+in	O
+group	O
+2	O
+during	O
+pacing	O
+.	O
+
+This	O
+was	O
+obtained	O
+with	O
+the	O
+thermal	O
+neutron	O
+fluency	O
+2	O
+.	O
+0	O
+x	O
+10	O
+(	O
+10	O
+)	O
+n	O
+/	O
+cm2	O
+.	O
+
+Endotoxemia	O
+induced	O
+by	O
+gram	O
+-	O
+negative	O
+bacteria	O
+leads	O
+to	O
+endotoxic	O
+shock	O
+pathogenetically	O
+stemming	O
+from	O
+the	O
+integral	O
+component	O
+of	O
+the	O
+bacterial	O
+wall	O
+-	O
+-	O
+lipid	O
+A	O
+.	O
+
+The	O
+study	O
+made	O
+to	O
+define	O
+the	O
+ability	O
+of	O
+lipid	B-GENE
+A	I-GENE
+monoclonal	I-GENE
+antibodies	I-GENE
+to	O
+correct	O
+hemodynamic	O
+disturbances	O
+due	O
+to	O
+endotoxemia	O
+in	O
+dog	O
+experiments	O
+showed	O
+the	O
+efficacy	O
+of	O
+the	O
+antibodies	O
+administration	O
+.	O
+
+A	O
+randomised	O
+,	O
+controlled	O
+trial	O
+was	O
+undertaken	O
+in	O
+40	O
+patients	O
+with	O
+active	O
+Crohn	O
+'	O
+s	O
+disease	O
+to	O
+evaluate	O
+clinical	O
+and	O
+nutritional	O
+outcomes	O
+after	O
+an	O
+amino	O
+acid	O
+based	O
+diet	O
+containing	O
+3	O
+%	O
+fat	O
+was	O
+given	O
+by	O
+a	O
+feeding	O
+tube	O
+compared	O
+with	O
+a	O
+peptide	O
+based	O
+diet	O
+containing	O
+33	O
+%	O
+fat	O
+.	O
+
+The	O
+sequenced	O
+genomic	O
+region	O
+thus	O
+accounts	O
+for	O
+essentially	O
+all	O
+of	O
+the	O
+longest	O
+known	O
+transcript	O
+(	O
+4	O
+.	O
+5	O
+kb	O
+)	O
+,	O
+although	O
+the	O
+precise	O
+ends	O
+of	O
+this	O
+transcript	O
+have	O
+not	O
+been	O
+defined	O
+.	O
+
+The	O
+pexB	B-GENE
+upstream	I-GENE
+region	I-GENE
+contained	O
+245	O
+nucleotides	O
+within	O
+which	O
+sequences	O
+approximating	O
+the	O
+consensus	O
+for	O
+cyclic	B-GENE
+AMP	I-GENE
+receptor	I-GENE
+protein	I-GENE
+and	O
+integration	B-GENE
+host	I-GENE
+factor	I-GENE
+binding	O
+sites	O
+were	O
+discernible	O
+.	O
+
+The	O
+fepA	B-GENE
+-	O
+entD	B-GENE
+and	O
+fes	B-GENE
+-	O
+entF	B-GENE
+operons	O
+in	O
+the	O
+enterobactin	O
+synthesis	O
+and	O
+transport	O
+system	O
+are	O
+divergently	O
+transcribed	O
+from	O
+overlapping	O
+promoters	O
+,	O
+and	O
+both	O
+are	O
+inhibited	O
+by	O
+the	O
+Fur	B-GENE
+repressor	I-GENE
+protein	I-GENE
+under	O
+iron	O
+-	O
+replete	O
+conditions	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+a	O
+6	O
+.	O
+3	O
+-	O
+kbp	O
+genomic	O
+EcoRI	B-GENE
+-	O
+fragment	O
+of	O
+Alcaligenes	O
+eutrophus	O
+,	O
+which	O
+was	O
+recently	O
+identified	O
+by	O
+using	O
+a	O
+dihydrolipoamide	B-GENE
+dehydrogenase	I-GENE
+-	O
+specific	O
+DNA	O
+probe	O
+(	O
+A	O
+.	O
+
+Using	O
+a	O
+previously	O
+published	O
+two	O
+-	O
+frequency	O
+(	O
+AC	O
+excitation	O
+)	O
+three	O
+-	O
+electrode	O
+method	O
+,	O
+the	O
+admittance	O
+locus	O
+plot	O
+(	O
+ALP	O
+)	O
+in	O
+the	O
+low	O
+-	O
+frequency	O
+region	O
+(	O
+<	O
+1000	O
+Hz	O
+)	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+very	O
+well	O
+approximated	O
+by	O
+a	O
+straight	O
+line	O
+and	O
+can	O
+be	O
+described	O
+with	O
+frequency	O
+-	O
+independent	O
+parameters	O
+;	O
+phase	O
+angle	O
+alpha	O
+pi	O
+/	O
+2	O
+,	O
+conductance	O
+at	O
+extrapolated	O
+zero	O
+frequency	O
+G0	O
+=	O
+1	O
+/	O
+R0	O
+,	O
+and	O
+ion	O
+relaxation	O
+time	O
+tau	O
+.	O
+
+Intraoperative	O
+measurement	O
+of	O
+activated	O
+partial	O
+thromboplastin	B-GENE
+time	O
+and	O
+prothrombin	B-GENE
+time	O
+with	O
+a	O
+new	O
+compact	O
+monitor	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+sought	O
+to	O
+test	O
+the	O
+hypothesis	O
+that	O
+,	O
+when	O
+equal	O
+volumes	O
+are	O
+administered	O
+intrathecally	O
+,	O
+significant	O
+differences	O
+exist	O
+in	O
+the	O
+potential	O
+to	O
+three	O
+commonly	O
+used	O
+anesthetic	O
+solutions	O
+to	O
+induce	O
+sensory	O
+impairment	O
+.	O
+
+In	O
+an	O
+in	O
+vitro	O
+study	O
+,	O
+10	O
+/	O
+0	O
+nylon	O
+was	O
+found	O
+to	O
+require	O
+a	O
+significantly	O
+lower	O
+laser	O
+energy	O
+density	O
+to	O
+produce	O
+suture	O
+lysis	O
+following	O
+a	O
+single	O
+shot	O
+than	O
+either	O
+10	O
+/	O
+0	O
+Dacron	O
+or	O
+10	O
+/	O
+0	O
+prolene	O
+.	O
+
+The	O
+proteins	O
+encoded	O
+downstream	O
+of	O
+rpoN	B-GENE
+are	O
+known	O
+to	O
+negatively	O
+regulate	O
+sigma	B-GENE
+54	I-GENE
+activity	O
+.	O
+
+We	O
+report	O
+here	O
+that	O
+microinjection	O
+of	O
+an	O
+anti	B-GENE
+-	I-GENE
+CBP	I-GENE
+antiserum	I-GENE
+into	O
+fibroblasts	O
+can	O
+inhibit	O
+transcription	O
+from	O
+a	O
+cAMP	O
+responsive	O
+promoter	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+a	O
+class	O
+of	O
+proline	O
+-	O
+rich	O
+activator	O
+proteins	O
+and	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+possess	O
+a	O
+common	O
+structural	O
+and	O
+functional	O
+component	O
+which	O
+can	O
+interact	O
+with	O
+the	O
+same	O
+target	O
+in	O
+the	O
+general	O
+transcription	O
+machinery	O
+.	O
+
+Cloning	O
+of	O
+higher	B-GENE
+plant	I-GENE
+omega	I-GENE
+-	I-GENE
+3	I-GENE
+fatty	I-GENE
+acid	I-GENE
+desaturases	I-GENE
+.	O
+
+65	O
+,	O
+3829	O
+-	O
+3838	O
+,	O
+1991	O
+)	O
+,	O
+a	O
+truncated	O
+form	O
+of	O
+the	O
+IE	B-GENE
+polypeptide	I-GENE
+lacking	O
+IE	B-GENE
+amino	I-GENE
+acid	I-GENE
+residues	I-GENE
+1	I-GENE
+-	I-GENE
+322	I-GENE
+(	O
+and	O
+,	O
+therefore	O
+lacks	O
+the	O
+deduced	O
+transcriptional	O
+activation	O
+domain	O
+)	O
+,	O
+fails	O
+to	O
+transactivate	O
+the	O
+EHV	B-GENE
+-	I-GENE
+1	I-GENE
+tk	I-GENE
+promoter	I-GENE
+,	O
+but	O
+retains	O
+the	O
+ability	O
+to	O
+down	O
+-	O
+regulate	O
+the	O
+EHV	B-GENE
+-	I-GENE
+1	I-GENE
+IE	I-GENE
+promoter	I-GENE
+.	O
+
+CONCLUSION	O
+:	O
+Human	O
+preterm	O
+birth	O
+is	O
+associated	O
+with	O
+significantly	O
+lower	O
+progesterone	O
+/	O
+17	O
+beta	O
+-	O
+estradiol	O
+ratios	O
+than	O
+those	O
+of	O
+women	O
+with	O
+preterm	O
+labor	O
+delivered	O
+at	O
+term	O
+.	O
+
+In	O
+conclusion	O
+,	O
+the	O
+disposition	O
+of	O
+venlafaxine	O
+and	O
+O	O
+-	O
+desmethylvenlafaxine	O
+is	O
+markedly	O
+altered	O
+in	O
+renal	O
+disease	O
+;	O
+therefore	O
+dosage	O
+adjustment	O
+is	O
+warranted	O
+for	O
+patients	O
+with	O
+creatinine	O
+clearance	O
+values	O
+below	O
+30	O
+ml	O
+/	O
+min	O
+.	O
+
+The	O
+availability	O
+of	O
+sequence	O
+from	O
+multiple	O
+species	O
+has	O
+permitted	O
+us	O
+to	O
+determine	O
+that	O
+the	O
+UBE	O
+site	O
+has	O
+close	O
+similarity	O
+to	O
+motifs	O
+that	O
+bind	O
+members	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+1	I-GENE
+family	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+The	O
+incidence	O
+of	O
+HSV	O
+-	O
+2	O
+positive	O
+subjects	O
+(	O
+HSV	B-GENE
+-	I-GENE
+2	I-GENE
+/	I-GENE
+HSV	I-GENE
+-	I-GENE
+1	I-GENE
+antibody	I-GENE
+ratio	O
+>	O
+or	O
+=	O
+1	O
+)	O
+was	O
+low	O
+in	O
+the	O
+Jewish	O
+Israeli	O
+population	O
+,	O
+compared	O
+to	O
+other	O
+demographic	O
+areas	O
+.	O
+
+The	O
+mechanism	O
+whereby	O
+zeta	B-GENE
+PKC	I-GENE
+regulates	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+most	O
+probably	O
+involves	O
+the	O
+activation	O
+of	O
+a	O
+putative	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+kinase	I-GENE
+of	O
+molecular	O
+mass	O
+approximately	O
+50	O
+kDa	O
+,	O
+which	O
+phosphorylates	O
+and	O
+inactivates	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+.	O
+
+Stable	O
+expression	O
+of	O
+truncated	B-GENE
+inositol	I-GENE
+1	I-GENE
+,	I-GENE
+4	I-GENE
+,	I-GENE
+5	I-GENE
+-	I-GENE
+trisphosphate	I-GENE
+receptor	I-GENE
+subunits	I-GENE
+in	O
+3T3	O
+fibroblasts	O
+.	O
+
+We	O
+report	O
+the	O
+identification	O
+and	O
+characterization	O
+of	O
+myr	B-GENE
+4	I-GENE
+(	O
+myosin	B-GENE
+from	I-GENE
+rat	I-GENE
+)	O
+,	O
+the	O
+first	O
+mammalian	B-GENE
+myosin	I-GENE
+I	I-GENE
+that	O
+is	O
+not	O
+closely	O
+related	O
+to	O
+brush	O
+border	O
+myosin	B-GENE
+I	I-GENE
+.	O
+
+M	O
+.	O
+,	O
+and	O
+D	O
+.	O
+
+In	O
+addition	O
+,	O
+computer	O
+analysis	O
+suggests	O
+that	O
+sequences	O
+similar	O
+to	O
+the	O
+A	O
+stem	O
+element	O
+are	O
+present	O
+within	O
+the	O
+three	O
+AAV	B-GENE
+promoter	I-GENE
+regions	O
+.	O
+
+At	O
+least	O
+some	O
+of	O
+the	O
+difference	O
+in	O
+stability	O
+of	O
+the	O
+two	O
+kinds	O
+of	O
+complexes	O
+was	O
+due	O
+to	O
+the	O
+fact	O
+that	O
+the	O
+dissociation	O
+rate	O
+of	O
+the	O
+A	O
+stem	O
+substrate	O
+from	O
+the	O
+protein	O
+-	O
+DNA	O
+complexes	O
+was	O
+approximately	O
+fourfold	O
+faster	O
+than	O
+that	O
+of	O
+the	O
+complete	O
+TR	B-GENE
+.	O
+
+Processing	O
+of	O
+the	O
+NS3	B-GENE
+'	I-GENE
+-	O
+5B	B-GENE
+polyprotein	O
+was	O
+complex	O
+and	O
+occurred	O
+rapidly	O
+.	O
+
+However	O
+,	O
+each	O
+promoter	O
+activated	O
+by	O
+IEP86	B-GENE
+was	O
+synergistically	O
+affected	O
+by	O
+the	O
+addition	O
+of	O
+IEP72	B-GENE
+.	O
+
+32Pi	O
+labeling	O
+or	O
+isoelectric	O
+focusing	O
+analysis	O
+of	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+from	O
+conditional	O
+casein	B-GENE
+kinase	I-GENE
+II	I-GENE
+mutants	I-GENE
+indicated	O
+that	O
+phosphorylation	O
+of	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+is	O
+abolished	O
+or	O
+dephosphorylated	O
+forms	O
+of	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+are	O
+detected	O
+when	O
+these	O
+strains	O
+are	O
+grown	O
+at	O
+the	O
+restrictive	O
+growth	O
+conditions	O
+.	O
+
+The	O
+R2	O
+region	O
+within	O
+the	O
+class	O
+I	O
+enhancer	O
+acts	O
+as	O
+a	O
+negative	O
+element	O
+in	O
+Ad12	O
+-	O
+transformed	O
+cells	O
+and	O
+exhibits	O
+a	O
+stronger	O
+binding	O
+activity	O
+than	O
+is	O
+observed	O
+in	O
+nontumorigenic	O
+Ad5	O
+-	O
+transformed	O
+cells	O
+,	O
+which	O
+are	O
+not	O
+reduced	O
+in	O
+class	O
+I	O
+expression	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+evaluate	O
+the	O
+kinetics	O
+of	O
+erythropoietin	B-GENE
+(	O
+EPO	B-GENE
+)	O
+production	O
+and	O
+address	O
+the	O
+pathogenesis	O
+of	O
+anemia	O
+of	O
+prematurity	O
+,	O
+we	O
+measured	O
+EPO	B-GENE
+levels	O
+in	O
+infants	O
+during	O
+the	O
+first	O
+year	O
+of	O
+life	O
+.	O
+
+The	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+beta	I-GENE
+gene	I-GENE
+(	O
+NGFB	B-GENE
+)	O
+belongs	O
+to	O
+a	O
+conserved	O
+syntenic	O
+group	O
+on	O
+human	O
+chromosome	O
+1	O
+and	O
+mouse	O
+Chromosome	O
+3	O
+.	O
+
+Furthermore	O
+,	O
+an	O
+upstream	O
+element	O
+,	O
+collagen	B-GENE
+element	I-GENE
+I	I-GENE
+(	I-GENE
+-	I-GENE
+370	I-GENE
+/	I-GENE
+-	I-GENE
+344	I-GENE
+)	I-GENE
+,	O
+which	O
+shares	O
+homology	O
+with	O
+the	O
+LAP	B-GENE
+binding	O
+cis	O
+-	O
+element	O
+of	O
+the	O
+albumin	B-GENE
+promoter	I-GENE
+(	O
+9	O
+of	O
+13	O
+bp	O
+)	O
+is	O
+described	O
+.	O
+
+Number	O
+and	O
+size	O
+of	O
+silver	O
+-	O
+stained	O
+nucleoli	O
+(	O
+Ag	O
+-	O
+NOR	O
+clusters	O
+)	O
+in	O
+canine	O
+seminomas	O
+:	O
+correlation	O
+with	O
+histological	O
+features	O
+and	O
+tumour	O
+behaviour	O
+.	O
+
+We	O
+speculate	O
+that	O
+mast	O
+cell	O
+degranulation	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+pathogenesis	O
+of	O
+necrobiosis	O
+by	O
+altering	O
+fibroblast	O
+enzyme	O
+activity	O
+and	O
+/	O
+or	O
+producing	O
+prolonged	O
+inflammatory	O
+reactions	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+a	O
+cysteine	B-GENE
+synthase	I-GENE
+cDNA	I-GENE
+from	O
+Citrullus	O
+vulgaris	O
+(	O
+watermelon	O
+)	O
+by	O
+genetic	O
+complementation	O
+in	O
+an	O
+Escherichia	O
+coli	O
+Cys	O
+-	O
+auxotroph	O
+.	O
+
+In	O
+earlier	O
+studies	O
+we	O
+identified	O
+several	O
+regulatory	O
+elements	O
+that	O
+control	O
+transcriptional	O
+activation	O
+and	O
+aerobic	O
+repression	O
+of	O
+one	O
+of	O
+these	O
+genes	O
+,	O
+COX5b	B-GENE
+.	O
+
+Although	O
+elevated	O
+serum	O
+levels	O
+of	O
+antibodies	O
+to	O
+the	O
+nicotinic	B-GENE
+acetylcholine	I-GENE
+receptor	I-GENE
+(	O
+nAChR	B-GENE
+)	O
+have	O
+been	O
+reported	O
+in	O
+neuroleptic	O
+treated	O
+patients	O
+with	O
+tardive	O
+dyskinesia	O
+,	O
+such	O
+antibodies	O
+have	O
+not	O
+been	O
+determined	O
+in	O
+comparable	O
+nondyskinetic	O
+patients	O
+.	O
+
+The	O
+tumor	O
+suppressor	O
+and	O
+transcriptional	O
+factor	O
+p53	B-GENE
+is	O
+a	O
+phosphorylated	O
+protein	O
+.	O
+
+This	O
+DNA	O
+containing	O
+promoter	O
+activity	O
+has	O
+been	O
+sequenced	O
+in	O
+its	O
+entirety	O
+and	O
+found	O
+to	O
+contain	O
+multiple	O
+putative	O
+regulatory	O
+sites	O
+.	O
+
+However	O
+,	O
+Southern	O
+blot	O
+and	O
+karyotype	O
+analyses	O
+did	O
+not	O
+reveal	O
+any	O
+significant	O
+changes	O
+in	O
+copy	O
+number	O
+or	O
+gross	O
+rearrangements	O
+of	O
+the	O
+p53	B-GENE
+gene	I-GENE
+in	O
+any	O
+of	O
+the	O
+p53	B-GENE
+-	I-GENE
+cell	O
+lines	O
+.	O
+
+HupI	B-GENE
+showed	O
+strong	O
+identity	O
+to	O
+rubredoxin	B-GENE
+and	O
+rubredoxin	B-GENE
+-	I-GENE
+like	I-GENE
+proteins	I-GENE
+from	O
+many	O
+other	O
+bacteria	O
+.	O
+
+The	O
+PCr	O
+resynthesis	O
+rate	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+and	O
+the	O
+effective	O
+maximal	O
+rate	O
+of	O
+mitochondrial	O
+ATP	O
+synthesis	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+also	O
+improved	O
+.	O
+
+An	O
+examination	O
+was	O
+performed	O
+in	O
+15	O
+patients	O
+who	O
+had	O
+developed	O
+pronounced	O
+osteomalacia	O
+following	O
+gastric	O
+resection	O
+.	O
+
+However	O
+,	O
+regional	O
+MVO2	O
+increased	O
+to	O
+about	O
+the	O
+same	O
+extent	O
+in	O
+the	O
+CFX	O
+(	O
+from	O
+6	O
+.	O
+0	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+to	O
+12	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+ml	O
+O2	O
+.	O
+min	O
+-	O
+1	O
+times	O
+100	O
+g	O
+-	O
+1	O
+)	O
+and	O
+the	O
+LAD	O
+region	O
+(	O
+from	O
+7	O
+.	O
+0	O
++	O
+/	O
+-	O
+0	O
+.	O
+6	O
+to	O
+14	O
+.	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+ml	O
+O2	O
+.	O
+min	O
+-	O
+1	O
+times	O
+100	O
+g	O
+-	O
+1	O
+)	O
+.	O
+
+IGF	B-GENE
+I	I-GENE
+and	O
+insulin	B-GENE
+receptors	I-GENE
+are	O
+homologous	O
+proteins	O
+that	O
+function	O
+in	O
+distinct	O
+physiological	O
+pathways	O
+.	O
+
+Immunodepression	O
+was	O
+combined	O
+with	O
+the	O
+increase	O
+of	O
+glucocorticoid	O
+activity	O
+of	O
+adrenal	O
+cortex	O
+,	O
+while	O
+no	O
+significant	O
+changes	O
+in	O
+thyroid	O
+hormones	O
+were	O
+registered	O
+.	O
+
+Aberrant	O
+protein	O
+phosphorylation	O
+at	O
+tyrosine	O
+is	O
+responsible	O
+for	O
+the	O
+growth	O
+-	O
+inhibitory	O
+action	O
+of	O
+pp60v	B-GENE
+-	I-GENE
+src	I-GENE
+expressed	O
+in	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Acute	O
+pancreatitis	O
+:	O
+a	O
+multisystem	O
+disease	O
+.	O
+
+Alginate	O
+biosynthesis	O
+is	O
+controlled	O
+by	O
+a	O
+complex	O
+regulatory	O
+mechanism	O
+.	O
+
+The	O
+sequence	O
+upstream	O
+of	O
+the	O
+rhlA	B-GENE
+promoter	I-GENE
+contains	O
+two	O
+inverted	O
+repeats	O
+which	O
+define	O
+putative	O
+binding	O
+sites	O
+for	O
+the	O
+RhlR	B-GENE
+regulator	I-GENE
+.	O
+
+We	O
+have	O
+examined	O
+by	O
+in	O
+vitro	O
+footprinting	O
+a	O
+region	O
+located	O
+downstream	O
+of	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+,	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+promoter	O
+found	O
+to	O
+be	O
+hypersensitive	O
+to	O
+DNase	B-GENE
+I	I-GENE
+digestion	O
+in	O
+vivo	O
+.	O
+
+The	O
+relative	O
+abundance	O
+of	O
+each	O
+alternatively	O
+spliced	O
+mRNA	O
+was	O
+determined	O
+by	O
+reverse	O
+transcription	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+in	O
+various	O
+human	O
+tissues	O
+and	O
+cell	O
+lines	O
+.	O
+
+The	O
+retention	O
+index	O
+of	O
+201Tl	O
+SPECT	O
+is	O
+a	O
+useful	O
+indicator	O
+of	O
+metastatic	O
+potential	O
+,	O
+thereby	O
+facilitating	O
+the	O
+prediction	O
+of	O
+prognosis	O
+,	O
+and	O
+provides	O
+insight	O
+into	O
+the	O
+relationship	O
+between	O
+201Tl	O
+uptake	O
+and	O
+malignancy	O
+.	O
+
+The	O
+central	O
+globular	O
+domain	O
+is	O
+highly	O
+similar	O
+to	O
+those	O
+regions	O
+from	O
+other	O
+H1	B-GENE
+molecules	I-GENE
+,	O
+and	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+domain	O
+contains	O
+a	O
+repeating	O
+hexapeptide	O
+motif	O
+,	O
+variants	O
+of	O
+which	O
+are	O
+conserved	O
+among	O
+H1	B-GENE
+molecules	I-GENE
+.	O
+
+The	O
+location	O
+and	O
+approximate	O
+length	O
+of	O
+the	O
+intron	O
+are	O
+conserved	O
+in	O
+both	O
+the	O
+tomato	O
+and	O
+Arabidopsis	O
+genes	O
+,	O
+with	O
+the	O
+intron	O
+separating	O
+the	O
+'	O
+nose	O
+'	O
+region	O
+(	O
+encoded	O
+by	O
+exon	O
+1	O
+)	O
+from	O
+the	O
+central	O
+globular	O
+domain	O
+(	O
+exon	O
+2	O
+)	O
+.	O
+
+The	O
+topology	O
+and	O
+chain	O
+folding	O
+of	O
+the	O
+beta	O
+subunits	O
+in	O
+the	O
+artifactual	O
+beta	O
+60	O
+capsid	O
+are	O
+similar	O
+to	O
+the	O
+native	B-GENE
+alpha	I-GENE
+3	I-GENE
+beta	I-GENE
+60	I-GENE
+enzyme	I-GENE
+.	O
+
+A	O
+constitutive	O
+mutant	O
+form	O
+with	O
+a	O
+single	O
+substitution	O
+(	O
+V88A	O
+)	O
+in	O
+the	O
+amino	O
+-	O
+terminal	O
+(	O
+response	O
+regulator	O
+)	O
+region	O
+was	O
+used	O
+.	O
+
+Comparisons	O
+of	O
+the	O
+four	O
+operon	O
+control	O
+regions	O
+studied	O
+indicate	O
+that	O
+the	O
+NarL	B-GENE
+heptamers	I-GENE
+are	O
+arranged	O
+with	O
+diverse	O
+orientations	O
+and	O
+spacing	O
+.	O
+
+Direct	O
+binding	O
+and	O
+competition	O
+assays	O
+using	O
+30	O
+-	O
+mer	O
+oligonucleotide	O
+probes	O
+representing	O
+the	O
+individual	O
+CBF1	B-GENE
+binding	I-GENE
+sites	I-GENE
+indicated	O
+that	O
+CBF1	B-GENE
+bound	O
+less	O
+efficiently	O
+to	O
+the	O
+CD23	B-GENE
+promoter	I-GENE
+and	O
+the	O
+EBV	B-GENE
+LMP	I-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+sites	I-GENE
+than	O
+to	O
+the	O
+Cp	B-GENE
+site	I-GENE
+.	O
+
+We	O
+have	O
+found	O
+a	O
+satisfactory	O
+reproducibility	O
+in	O
+vitro	O
+(	O
+T1	O
+:	O
+1	O
+.	O
+9	O
+%	O
+;	O
+T2	O
+:	O
+6	O
+.	O
+2	O
+%	O
+)	O
+,	O
+while	O
+the	O
+reproducibility	O
+was	O
+less	O
+satisfactory	O
+in	O
+vivo	O
+(	O
+T1	O
+:	O
+16	O
+.	O
+4	O
+%	O
+;	O
+T2	O
+:	O
+13	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+Sonographic	O
+angiography	O
+has	O
+a	O
+possible	O
+role	O
+in	O
+the	O
+detection	O
+of	O
+small	O
+nodules	O
+in	O
+patients	O
+with	O
+CRF	O
+.	O
+
+Each	O
+expressed	O
+domain	O
+,	O
+as	O
+well	O
+as	O
+FKBP	B-GENE
+-	I-GENE
+33	I-GENE
+itself	O
+,	O
+possesses	O
+peptidyl	B-GENE
+-	I-GENE
+prolyl	I-GENE
+cis	I-GENE
+-	I-GENE
+trans	I-GENE
+isomerase	I-GENE
+activity	O
+,	O
+though	O
+with	O
+much	O
+lower	O
+specific	O
+activities	O
+than	O
+FKBP	B-GENE
+-	I-GENE
+12	I-GENE
+.	O
+
+The	O
+first	O
+85	O
+nt	O
+upstream	O
+of	O
+the	O
+transcription	O
+initiation	O
+site	O
+of	O
+the	O
+mouse	B-GENE
+desmin	I-GENE
+gene	I-GENE
+,	O
+which	O
+contain	O
+an	O
+E	O
+box	O
+(	O
+E1	O
+)	O
+,	O
+the	O
+binding	O
+site	O
+of	O
+the	O
+helix	B-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+myogenic	I-GENE
+regulators	I-GENE
+,	O
+are	O
+sufficient	O
+to	O
+confer	O
+low	O
+level	O
+muscle	O
+-	O
+specific	O
+expression	O
+.	O
+
+The	O
+acfD	B-GENE
+gene	I-GENE
+encompasses	O
+254	O
+nt	O
+that	O
+are	O
+predicted	O
+to	O
+encode	O
+an	O
+88	O
+-	O
+amino	O
+-	O
+acid	O
+(	O
+aa	O
+)	O
+protein	O
+.	O
+
+We	O
+find	O
+that	O
+beta	B-GENE
+II	I-GENE
+PKC	I-GENE
+phosphorylates	O
+nuclear	B-GENE
+envelope	I-GENE
+lamin	I-GENE
+B	I-GENE
+at	O
+10	O
+-	O
+20	O
+times	O
+the	O
+rate	O
+of	O
+alpha	B-GENE
+PKC	I-GENE
+,	O
+whereas	O
+both	O
+kinases	O
+phosphorylate	O
+soluble	B-GENE
+lamin	I-GENE
+B	I-GENE
+at	O
+similar	O
+rates	O
+.	O
+
+Regulation	O
+of	O
+parathyroid	B-GENE
+hormone	I-GENE
+-	I-GENE
+related	I-GENE
+protein	I-GENE
+(	O
+PTHrP	B-GENE
+)	O
+gene	O
+expression	O
+.	O
+
+We	O
+conclude	O
+that	O
+c	B-GENE
+-	I-GENE
+Abl	I-GENE
+activates	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+transcription	O
+indirectly	O
+with	O
+no	O
+requirement	O
+for	O
+DNA	O
+binding	O
+by	O
+c	B-GENE
+-	I-GENE
+Abl	I-GENE
+.	O
+
+Long	O
+-	O
+latency	O
+:	O
+locked	O
+units	O
+responded	O
+to	O
+shocks	O
+with	O
+little	O
+jitter	O
+and	O
+long	O
+latency	O
+(	O
+4	O
+-	O
+11	O
+ms	O
+)	O
+.	O
+
+The	O
+highly	O
+conserved	O
+ninth	O
+heptad	O
+,	O
+which	O
+is	O
+involved	O
+in	O
+heterodimerization	O
+,	O
+appears	O
+to	O
+participate	O
+in	O
+the	O
+receptor	O
+-	O
+inhibitor	O
+interaction	O
+,	O
+suggesting	O
+that	O
+the	O
+inhibitor	O
+is	O
+a	O
+related	O
+member	O
+of	O
+the	O
+receptor	O
+gene	O
+family	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+for	O
+expression	O
+of	O
+snRNA	O
+genes	O
+in	O
+maize	O
+,	O
+a	O
+monocotyledonous	O
+plant	O
+,	O
+the	O
+USE	O
+and	O
+TATA	O
+elements	O
+are	O
+essential	O
+,	O
+but	O
+not	O
+sufficient	O
+,	O
+for	O
+transcription	O
+.	O
+
+Extensive	O
+DNA	O
+rearrangement	O
+occurs	O
+during	O
+the	O
+development	O
+of	O
+the	O
+somatic	O
+macronucleus	O
+from	O
+the	O
+germ	O
+line	O
+micronucleus	O
+in	O
+ciliated	O
+protozoans	O
+.	O
+
+An	O
+in	O
+vitro	O
+binding	O
+site	O
+selection	O
+procedure	O
+was	O
+used	O
+to	O
+determine	O
+DNA	O
+sequences	O
+preferentially	O
+bound	O
+by	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+HLF	I-GENE
+and	O
+chimeric	O
+E2A	B-GENE
+-	O
+HLF	B-GENE
+proteins	O
+isolated	O
+from	O
+various	O
+t	O
+(	O
+17	O
+;	O
+19	O
+)	O
+-	O
+bearing	O
+leukemias	O
+.	O
+
+The	O
+Oct	B-GENE
+-	I-GENE
+2	I-GENE
+glutamine	O
+-	O
+rich	O
+and	O
+proline	O
+-	O
+rich	O
+activation	O
+domains	O
+can	O
+synergize	O
+with	O
+each	O
+other	O
+or	O
+duplicates	O
+of	O
+themselves	O
+to	O
+activate	O
+transcription	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+Dbf8p	B-GENE
+plays	O
+an	O
+essential	O
+role	O
+in	O
+chromosome	O
+segregation	O
+.	O
+
+Ariga	O
+,	O
+Biochem	O
+.	O
+
+The	O
+diagnostic	O
+significance	O
+of	O
+creatine	B-GENE
+phosphokinase	I-GENE
+antibodies	O
+in	O
+the	O
+cardiac	O
+muscle	O
+in	O
+non	O
+-	O
+coronarogenic	O
+myocardial	O
+diseases	O
+
+According	O
+to	O
+the	O
+results	O
+of	O
+assays	O
+obtained	O
+with	O
+the	O
+use	O
+of	O
+assay	O
+systems	O
+ORTHO	O
+ELISA	O
+and	O
+ABBOTT	O
+HCV	O
+EIA	O
+(	O
+USA	O
+)	O
+,	O
+the	O
+detection	O
+rate	O
+of	O
+anti	B-GENE
+-	I-GENE
+HCV	I-GENE
+-	I-GENE
+C100	I-GENE
+-	I-GENE
+3	I-GENE
+among	O
+primary	O
+blood	O
+donors	O
+in	O
+Moscow	O
+was	O
+1	O
+.	O
+37	O
+%	O
+and	O
+was	O
+not	O
+different	O
+from	O
+that	O
+among	O
+HBsAg	B-GENE
+carriers	O
+(	O
+1	O
+.	O
+8	O
+%	O
+)	O
+and	O
+among	O
+donors	O
+with	O
+anti	B-GENE
+-	I-GENE
+HCV	I-GENE
+-	I-GENE
+C100	I-GENE
+-	I-GENE
+3	I-GENE
+in	O
+the	O
+blood	O
+(	O
+1	O
+.	O
+6	O
+%	O
+)	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+We	O
+examined	O
+the	O
+hypothesis	O
+that	O
+the	O
+coronary	O
+vasomotor	O
+responses	O
+to	O
+etomidate	O
+(	O
+ETO	O
+)	O
+,	O
+propofol	O
+(	O
+PRO	O
+)	O
+,	O
+and	O
+sodium	O
+thiopental	O
+(	O
+STP	O
+)	O
+are	O
+mediated	O
+through	O
+contrasting	O
+effects	O
+on	O
+the	O
+resting	O
+nitric	O
+oxide	O
+(	O
+NO	O
+)	O
+-	O
+dependent	O
+vasodilator	O
+tone	O
+that	O
+opposes	O
+adrenergic	O
+vasoconstrictor	O
+activity	O
+in	O
+the	O
+intact	O
+dog	O
+.	O
+
+These	O
+alternative	O
+splice	O
+variants	O
+were	O
+detected	O
+in	O
+RNA	O
+isolated	O
+from	O
+several	O
+sources	O
+,	O
+including	O
+primary	O
+leptomeningeal	O
+tissue	O
+and	O
+an	O
+established	O
+line	O
+of	O
+leptomeningeal	O
+cells	O
+(	O
+LMC	O
+)	O
+.	O
+
+Roux	O
+-	O
+en	O
+-	O
+Y	O
+gastroenterostomy	O
+severely	O
+disturbs	O
+emptying	O
+of	O
+the	O
+gallbladder	O
+.	O
+
+Surface	O
+-	O
+coil	O
+experiments	O
+on	O
+phantoms	O
+and	O
+on	O
+human	O
+calf	O
+muscles	O
+in	O
+vivo	O
+are	O
+presented	O
+.	O
+
+Large	O
+interpatient	O
+variation	O
+in	O
+peak	O
+PCZ	O
+plasma	O
+levels	O
+(	O
+91	O
+-	O
+3215	O
+ng	O
+/	O
+ml	O
+)	O
+was	O
+seen	O
+,	O
+with	O
+the	O
+plasma	O
+half	O
+-	O
+life	O
+(	O
+t1	O
+/	O
+2	O
+alpha	O
+)	O
+being	O
+approximately	O
+57	O
+min	O
+in	O
+patients	O
+given	O
+135	O
+-	O
+180	O
+mg	O
+/	O
+m2	O
+PCZ	O
+.	O
+
+The	O
+maximal	O
+effect	O
+was	O
+seen	O
+at	O
+100	O
+ng	O
+/	O
+ml	O
+EGF	B-GENE
+,	O
+with	O
+a	O
+time	O
+lag	O
+of	O
+about	O
+5	O
+h	O
+.	O
+
+KAR1	B-GENE
+encodes	O
+an	O
+essential	O
+component	O
+of	O
+the	O
+yeast	O
+spindle	O
+pole	O
+body	O
+(	O
+SPB	O
+)	O
+that	O
+is	O
+required	O
+for	O
+karyogamy	O
+and	O
+SPB	O
+duplication	O
+.	O
+
+CDC31	B-GENE
+is	O
+required	O
+for	O
+SPB	O
+duplication	O
+and	O
+encodes	O
+a	O
+calmodulin	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+that	O
+is	O
+most	O
+closely	O
+related	O
+to	O
+caltractin	B-GENE
+/	O
+centrin	B-GENE
+,	O
+a	O
+protein	O
+associated	O
+with	O
+the	O
+Chlamydomonas	O
+basal	O
+body	O
+.	O
+
+During	O
+transcript	O
+elongation	O
+,	O
+the	O
+sizes	O
+of	O
+the	O
+DNA	O
+footprint	O
+and	O
+the	O
+single	O
+-	O
+stranded	O
+transcription	O
+bubble	O
+vary	O
+markedly	O
+among	O
+transcription	O
+complexes	O
+halted	O
+at	O
+different	O
+template	O
+positions	O
+.	O
+
+All	O
+our	O
+patients	O
+had	O
+polyps	O
+,	O
+23	O
+(	O
+54	O
+%	O
+)	O
+had	O
+asthma	O
+,	O
+12	O
+(	O
+27	O
+%	O
+)	O
+had	O
+aspirin	O
+sensitivity	O
+,	O
+20	O
+(	O
+65	O
+%	O
+)	O
+had	O
+eosinophilia	O
+,	O
+and	O
+9	O
+(	O
+69	O
+%	O
+)	O
+had	O
+increased	O
+total	O
+IgE	B-GENE
+levels	O
+.	O
+
+A	O
+new	O
+generation	O
+of	O
+information	O
+retrieval	O
+tools	O
+for	O
+biologists	O
+:	O
+the	O
+example	O
+of	O
+the	O
+ExPASy	O
+WWW	O
+server	O
+.	O
+
+The	O
+partial	O
+ORF	O
+was	O
+found	O
+to	O
+be	O
+identical	O
+to	O
+the	O
+C	O
+terminus	O
+of	O
+HrpJ2	B-GENE
+.	O
+
+The	O
+partial	O
+ORF	O
+was	O
+found	O
+to	O
+be	O
+identical	O
+to	O
+the	O
+C	O
+terminus	O
+of	O
+HrpJ2	B-GENE
+.	O
+
+Rapid	O
+detection	O
+of	O
+this	O
+mutation	O
+is	O
+achieved	O
+by	O
+restriction	O
+digestion	O
+of	O
+PCR	O
+-	O
+amplified	O
+genomic	O
+DNA	O
+;	O
+a	O
+mismatch	O
+primer	O
+combined	O
+with	O
+the	O
+point	O
+mutation	O
+creates	O
+a	O
+Tru9I	B-GENE
+restriction	I-GENE
+site	I-GENE
+.	O
+
+Wild	B-GENE
+type	I-GENE
+and	I-GENE
+mutant	I-GENE
+Epo	I-GENE
+cDNAs	I-GENE
+were	O
+transiently	O
+expressed	O
+at	O
+high	O
+levels	O
+in	O
+COS1	O
+and	O
+COS7	O
+cells	O
+.	O
+
+OBJECTIVE	O
+-	O
+-	O
+To	O
+assess	O
+the	O
+risk	O
+of	O
+hepatitis	O
+A	O
+in	O
+international	O
+travelers	O
+and	O
+to	O
+recommend	O
+preventive	O
+measures	O
+.	O
+
+The	O
+bactericidal	O
+effect	O
+of	O
+disinfectants	O
+against	O
+biofilm	O
+cells	O
+was	O
+found	O
+to	O
+be	O
+considerably	O
+enhanced	O
+by	O
+increasing	O
+the	O
+concentrations	O
+of	O
+the	O
+disinfectants	O
+.	O
+
+Expression	O
+of	O
+ME31B	B-GENE
+cDNA	I-GENE
+in	O
+S	O
+.	O
+pombe	O
+suppresses	O
+the	O
+ste13	B-GENE
+mutation	O
+.	O
+
+Use	O
+of	O
+Medi	O
+-	O
+Jector	O
+EZ	O
+dermojet	O
+for	O
+anesthesia	O
+in	O
+minor	O
+surgery	O
+
+The	O
+immune	O
+response	O
+of	O
+past	O
+-	O
+infection	O
+of	O
+cytomegalovirus	O
+in	O
+the	O
+patients	O
+of	O
+RTID	O
+is	O
+rather	O
+remarkable	O
+.	O
+
+Acupuncture	O
+effect	O
+on	O
+deep	O
+receptors	O
+was	O
+not	O
+limited	O
+to	O
+one	O
+point	O
+but	O
+within	O
+a	O
+certain	O
+area	O
+,	O
+namely	O
+distant	O
+effect	O
+existed	O
+.	O
+
+Reduced	O
+NK	O
+activity	O
+correlates	O
+with	O
+active	O
+disease	O
+in	O
+HIV	O
+-	O
+patients	O
+with	O
+multidrug	O
+-	O
+resistant	O
+pulmonary	O
+tuberculosis	O
+.	O
+
+Smoking	O
+history	O
+and	O
+awake	O
+oxygen	O
+saturation	O
+(	O
+SaO2	O
+)	O
+was	O
+recorded	O
+in	O
+all	O
+of	O
+them	O
+.	O
+
+(	O
+LH	B-GENE
+P	O
+<	O
+0	O
+.	O
+05	O
+,	O
+LH	B-GENE
+/	O
+FSH	B-GENE
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+relative	O
+R	O
+-	O
+and	O
+L	O
+-	O
+brain	O
+weights	O
+were	O
+found	O
+to	O
+be	O
+inversely	O
+related	O
+to	O
+the	O
+relative	O
+R	O
+-	O
+L	O
+brain	O
+weight	O
+only	O
+in	O
+the	O
+RH	O
+female	O
+cats	O
+with	O
+R	O
+-	O
+L	O
+brain	O
+weight	O
+smaller	O
+than	O
+zero	O
+(	O
+testosterone	O
+in	O
+males	O
+,	O
+estrogen	O
+in	O
+females	O
+)	O
+.	O
+
+This	O
+mode	O
+of	O
+ternary	O
+complex	O
+formation	O
+is	O
+in	O
+contrast	O
+to	O
+the	O
+one	O
+seen	O
+in	O
+the	O
+promoter	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+protooncogene	I-GENE
+,	O
+where	O
+formation	O
+of	O
+the	O
+ternary	O
+complex	O
+is	O
+dependent	O
+on	O
+the	O
+prior	O
+assembly	O
+of	O
+the	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+-	I-GENE
+DNA	I-GENE
+binary	I-GENE
+complex	I-GENE
+.	O
+
+Vaccinia	O
+virus	O
+-	O
+expressed	O
+,	O
+purified	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+HPV	I-GENE
+-	I-GENE
+16	I-GENE
+and	I-GENE
+BPV	I-GENE
+-	I-GENE
+1	I-GENE
+E2	I-GENE
+proteins	I-GENE
+bound	O
+a	O
+consensus	O
+E2	B-GENE
+site	I-GENE
+with	O
+high	O
+specific	O
+affinities	O
+(	O
+Kd	O
+=	O
+approximately	O
+10	O
+(	O
+-	O
+9	O
+)	O
+M	O
+)	O
+and	O
+stimulated	O
+in	O
+vitro	O
+transcription	O
+up	O
+to	O
+six	O
+-	O
+to	O
+eightfold	O
+.	O
+
+This	O
+alternatively	O
+spliced	O
+transcript	O
+contained	O
+an	O
+open	O
+reading	O
+frame	O
+extending	O
+from	O
+the	O
+upstream	O
+J	O
+alpha	O
+11	O
+-	O
+2	O
+region	O
+to	O
+82	O
+nucleotides	O
+downstream	O
+of	O
+the	O
+beginning	O
+of	O
+the	O
+TCR	B-GENE
+C	I-GENE
+alpha	I-GENE
+region	I-GENE
+,	O
+and	O
+potentially	O
+encoded	O
+a	O
+36	O
+amino	O
+acid	O
+polypeptide	O
+.	O
+
+In	O
+HeLa	O
+x	O
+fibroblast	O
+cell	O
+hybrids	O
+its	O
+expression	O
+correlates	O
+with	O
+tumorigenicity	O
+.	O
+
+Demographic	O
+characteristics	O
+and	O
+risk	O
+factor	O
+data	O
+for	O
+76	O
+,	O
+672	O
+clients	O
+were	O
+studied	O
+to	O
+characterize	O
+the	O
+distribution	O
+of	O
+infection	O
+with	O
+human	O
+immunodeficiency	O
+virus	O
+(	O
+HIV	O
+)	O
+and	O
+the	O
+use	O
+of	O
+counseling	O
+and	O
+testing	O
+facilities	O
+in	O
+Houston	O
+,	O
+Tex	O
+.	O
+
+Results	O
+indicate	O
+that	O
+KNM	O
+-	O
+LU	O
+335	O
+differs	O
+from	O
+both	O
+human	O
+and	O
+chimpanzee	O
+M1s	O
+in	O
+relative	O
+distances	O
+(	O
+measured	O
+in	O
+three	O
+dimensions	O
+)	O
+between	O
+crown	O
+fissure	O
+termini	O
+.	O
+
+We	O
+describe	O
+49	O
+cases	O
+with	O
+papillary	O
+tumor	O
+<	O
+1	O
+cm	O
+.	O
+
+Comparison	O
+with	O
+the	O
+bovine	O
+gene	O
+showed	O
+that	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+hATP1	B-GENE
+gene	I-GENE
+has	O
+an	O
+unconserved	O
+guanine	O
+-	O
+cytosine	O
+(	O
+GC	O
+)	O
+rich	O
+region	O
+,	O
+including	O
+several	O
+binding	O
+motifs	O
+of	O
+transcriptional	O
+factors	O
+,	O
+such	O
+as	O
+Sp1	B-GENE
+,	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+and	O
+GCF	B-GENE
+.	O
+
+Structure	O
+,	O
+promoter	O
+analysis	O
+and	O
+chromosomal	O
+assignment	O
+of	O
+the	O
+human	B-GENE
+APEX	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+polyubiquitin	B-GENE
+gene	I-GENE
+was	O
+transcribed	O
+throughout	O
+the	O
+Volvox	O
+life	O
+cycle	O
+with	O
+peaks	O
+in	O
+the	O
+1	O
+.	O
+6	O
+-	O
+kb	O
+mRNA	O
+levels	O
+during	O
+pre	O
+-	O
+cleavage	O
+,	O
+cleavage	O
+,	O
+and	O
+post	O
+-	O
+inversion	O
+.	O
+
+Thus	O
+,	O
+in	O
+stress	O
+-	O
+induced	O
+arrhythmic	O
+disease	O
+as	O
+well	O
+as	O
+in	O
+ischemic	O
+heart	O
+disease	O
+,	O
+the	O
+main	O
+pathogenetic	O
+links	O
+are	O
+outside	O
+the	O
+heart	O
+,	O
+but	O
+they	O
+differ	O
+from	O
+those	O
+observed	O
+in	O
+ischemia	O
+.	O
+
+Here	O
+,	O
+we	O
+present	O
+genetic	O
+evidence	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+for	O
+a	O
+functional	O
+interaction	O
+between	O
+the	O
+DEAH	B-GENE
+protein	I-GENE
+Prp16	B-GENE
+,	O
+and	O
+the	O
+U6	B-GENE
+and	O
+U2	B-GENE
+spliceosomal	I-GENE
+snRNAs	I-GENE
+.	O
+
+The	O
+consensus	O
+gene	O
+order	O
+deduced	O
+by	O
+combining	O
+data	O
+from	O
+both	O
+crosses	O
+is	O
+D2Mit1	B-GENE
+-	O
+(	O
+Dbh	B-GENE
+,	O
+Notch1	B-GENE
+)	O
+-	O
+(	O
+Col5a1	B-GENE
+,	O
+Rxra	B-GENE
+)	O
+-	O
+Spna2	B-GENE
+-	O
+Ab	B-GENE
+l	I-GENE
+-	O
+(	O
+Ak1	B-GENE
+,	O
+Fpgs	B-GENE
+)	O
+-	O
+(	O
+Grp78	B-GENE
+,	O
+Pbx3	B-GENE
+)	O
+-	O
+(	O
+Epb7	B-GENE
+.	I-GENE
+2	I-GENE
+,	I-GENE
+Hc	I-GENE
+,	I-GENE
+Gsn	I-GENE
+)	O
+-	O
+Acra	B-GENE
+.	O
+
+The	O
+high	O
+level	O
+of	O
+transformation	O
+-	O
+associated	O
+deletions	O
+in	O
+the	O
+human	O
+YACs	O
+was	O
+reduced	O
+over	O
+10	O
+-	O
+fold	O
+when	O
+the	O
+host	O
+was	O
+a	O
+recombination	O
+-	O
+deficient	O
+strain	O
+deleted	O
+for	O
+the	O
+RAD52	B-GENE
+gene	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+megabase	O
+region	O
+surrounding	O
+the	O
+dagA	B-GENE
+locus	I-GENE
+was	O
+mapped	O
+.	O
+
+These	O
+mutants	O
+had	O
+deletions	O
+of	O
+the	O
+extreme	O
+amino	O
+-	O
+terminal	O
+residues	O
+as	O
+far	O
+as	O
+amino	O
+acid	O
+residue	O
+30	O
+.	O
+
+SECONDARY	O
+OUTCOME	O
+MEASURE	O
+-	O
+-	O
+Double	O
+-	O
+blind	O
+caffeine	O
+-	O
+withdrawal	O
+evaluation	O
+.	O
+
+Elimination	O
+of	O
+natural	O
+antibodies	O
+in	O
+discordant	O
+xenografts	O
+
+An	O
+8	O
+-	O
+bp	O
+sequence	O
+(	O
+ATTTCAAA	O
+)	O
+within	O
+the	O
+protected	O
+region	O
+shares	O
+significant	O
+homology	O
+with	O
+promoter	O
+sequences	O
+required	O
+for	O
+ethylene	O
+responsiveness	O
+from	O
+the	O
+tomato	O
+fruit	O
+-	O
+ripening	O
+E4	B-GENE
+gene	I-GENE
+.	O
+
+We	O
+present	O
+evidence	O
+that	O
+DNA	B-GENE
+polymerase	I-GENE
+delta	I-GENE
+of	I-GENE
+Saccharomyces	I-GENE
+cerevisiae	I-GENE
+,	O
+an	O
+enzyme	O
+that	O
+is	O
+essential	O
+for	O
+viability	O
+and	O
+chromosomal	O
+replication	O
+,	O
+is	O
+also	O
+required	O
+for	O
+base	O
+excision	O
+repair	O
+of	O
+exogenous	O
+DNA	O
+methylation	O
+damage	O
+.	O
+
+We	O
+have	O
+identified	O
+two	O
+Marek	O
+'	O
+s	O
+Disease	O
+Virus	O
+(	O
+MDV	O
+)	O
+genes	O
+within	O
+the	O
+EcoRI	B-GENE
+-	I-GENE
+B	I-GENE
+fragment	I-GENE
+of	O
+MDV	O
+-	O
+GA	O
+genomic	O
+DNA	O
+.	O
+
+Cowpox	O
+virus	O
+contains	O
+two	O
+copies	O
+of	O
+an	O
+early	B-GENE
+gene	I-GENE
+encoding	O
+a	O
+soluble	O
+secreted	O
+form	O
+of	O
+the	O
+type	B-GENE
+II	I-GENE
+TNF	I-GENE
+receptor	I-GENE
+.	O
+
+Mutagenesis	O
+of	O
+each	O
+NRF	B-GENE
+-	I-GENE
+1	I-GENE
+motif	I-GENE
+in	O
+the	O
+ALAS	B-GENE
+promoter	I-GENE
+gave	O
+substantially	O
+lowered	O
+levels	O
+of	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+expression	O
+,	O
+whereas	O
+mutagenesis	O
+of	O
+both	O
+NRF	B-GENE
+-	I-GENE
+1	I-GENE
+motifs	I-GENE
+resulted	O
+in	O
+the	O
+almost	O
+complete	O
+loss	O
+of	O
+expression	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+analysis	O
+indicated	O
+that	O
+DREF	B-GENE
+binds	O
+to	O
+the	O
+24	O
+-	O
+bp	O
+DRE	O
+region	O
+of	O
+the	O
+DNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+gene	I-GENE
+in	O
+which	O
+8	O
+-	O
+bp	O
+palindromic	O
+sequences	O
+are	O
+centered	O
+.	O
+
+Novel	O
+8	O
+-	O
+base	O
+pair	O
+sequence	O
+(	O
+Drosophila	O
+DNA	O
+replication	O
+-	O
+related	O
+element	O
+)	O
+and	O
+specific	O
+binding	O
+factor	O
+involved	O
+in	O
+the	O
+expression	O
+of	O
+Drosophila	O
+genes	O
+for	O
+DNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+and	O
+proliferating	B-GENE
+cell	I-GENE
+nuclear	I-GENE
+antigen	I-GENE
+.	O
+
+Most	O
+,	O
+however	O
+,	O
+would	O
+tell	O
+the	O
+spouse	O
+the	O
+full	O
+truth	O
+about	O
+both	O
+diagnosis	O
+and	O
+prognosis	O
+.	O
+
+Metabolism	O
+of	O
+calcium	O
+and	O
+vitamin	O
+D3	O
+in	O
+patients	O
+with	O
+acute	O
+tubulointerstitial	O
+nephritis	O
+:	O
+a	O
+study	O
+of	O
+41	O
+patients	O
+with	O
+nephropathia	O
+epidemica	O
+.	O
+
+Furthermore	O
+,	O
+this	O
+study	O
+demonstrates	O
+that	O
+reduced	O
+inotropy	O
+with	O
+timolol	O
+helped	O
+uniform	O
+local	O
+contraction	O
+as	O
+estimated	O
+by	O
+the	O
+increased	O
+LONG	O
+/	O
+CIRC	O
+ratio	O
+,	O
+a	O
+transition	O
+that	O
+could	O
+improve	O
+contraction	O
+efficacy	O
+.	O
+
+Effects	O
+of	O
+moderate	O
+hypercapnia	O
+on	O
+hypothermia	O
+induced	O
+by	O
+cold	O
+He	O
+-	O
+O2	O
+in	O
+rats	O
+.	O
+
+We	O
+recommend	O
+that	O
+ovarian	O
+stimulation	O
+is	O
+done	O
+only	O
+if	O
+there	O
+is	O
+a	O
+valid	O
+indication	O
+after	O
+proper	O
+assessment	O
+of	O
+the	O
+ovaries	O
+,	O
+and	O
+that	O
+women	O
+who	O
+have	O
+had	O
+ovarian	O
+stimulation	O
+are	O
+followed	O
+for	O
+longer	O
+than	O
+at	O
+present	O
+.	O
+
+A23187	O
+did	O
+not	O
+induce	O
+any	O
+modifications	O
+of	O
+the	O
+endolymphatic	O
+potential	O
+,	O
+the	O
+ampullar	O
+direct	O
+current	O
+or	O
+the	O
+frequency	O
+of	O
+the	O
+evoked	O
+afferent	O
+spikes	O
+.	O
+
+Activation	O
+of	O
+the	O
+aboral	O
+ectoderm	B-GENE
+-	I-GENE
+specific	I-GENE
+Spec2a	I-GENE
+gene	I-GENE
+in	O
+blastula	O
+-	O
+stage	O
+sea	O
+urchin	O
+embryos	O
+requires	O
+an	O
+upstream	O
+regulatory	O
+region	O
+that	O
+is	O
+part	O
+of	O
+a	O
+repetitive	O
+sequence	O
+element	O
+(	O
+RSR	O
+)	O
+associated	O
+with	O
+all	O
+Spec1	B-GENE
+/	O
+Spec2	B-GENE
+genes	O
+.	O
+
+A	O
+transcript	O
+of	O
+about	O
+2	O
+kb	O
+is	O
+expected	O
+for	O
+each	O
+PPO	B-GENE
+.	O
+
+Mutations	O
+in	O
+a	O
+region	O
+located	O
+15	O
+to	O
+30	O
+bp	O
+downstream	O
+from	O
+the	O
+major	O
+transcription	O
+start	O
+site	O
+that	O
+shows	O
+good	O
+homology	O
+to	O
+a	O
+sequence	O
+in	O
+the	O
+first	O
+exon	O
+of	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+implicated	O
+as	O
+a	O
+negative	O
+regulatory	O
+element	O
+resulted	O
+in	O
+a	O
+significant	O
+increase	O
+in	O
+basal	O
+gene	O
+expression	O
+but	O
+did	O
+not	O
+affect	O
+regulation	O
+.	O
+
+Salazopyrine	O
+desensitization	O
+
+During	O
+exercise	O
+,	O
+the	O
+Pes	O
+-	O
+Ves	O
+relation	O
+was	O
+shifted	O
+toward	O
+the	O
+left	O
+and	O
+the	O
+slope	O
+[	O
+end	O
+-	O
+systolic	O
+elastance	O
+(	O
+Ees	O
+)	O
+]	O
+increased	O
+from	O
+7	O
+.	O
+7	O
++	O
+/	O
+-	O
+2	O
+.	O
+8	O
+to	O
+12	O
+.	O
+7	O
++	O
+/	O
+-	O
+4	O
+.	O
+2	O
+(	O
+SD	O
+)	O
+mmHg	O
+/	O
+ml	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+We	O
+show	O
+that	O
+HRI	B-GENE
+and	O
+dsRNA	B-GENE
+-	I-GENE
+PK	I-GENE
+phosphorylate	O
+yeast	B-GENE
+eIF	I-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+and	O
+functionally	O
+substitute	O
+for	O
+GCN2	B-GENE
+protein	I-GENE
+to	O
+stimulate	O
+GCN4	B-GENE
+translation	O
+in	O
+yeast	O
+.	O
+
+Double	O
+-	O
+staining	O
+confirmed	O
+that	O
+there	O
+were	O
+separate	O
+populations	O
+of	O
+CD68	B-GENE
+-	O
+positive	O
+macrophages	O
+and	O
+XIIIa	B-GENE
+-	O
+positive	O
+dendrocytes	O
+.	O
+
+Interestingly	O
+,	O
+in	O
+the	O
+adult	O
+,	O
+transgene	O
+expression	O
+patterns	O
+within	O
+the	O
+cerebellum	O
+in	O
+two	O
+lines	O
+appeared	O
+to	O
+mark	O
+distinct	O
+anterior	O
+-	O
+posterior	O
+compartments	O
+.	O
+
+The	O
+concentrations	O
+of	O
+plasma	O
+ACTH	B-GENE
+and	O
+cortisol	O
+increased	O
+by	O
+40	O
+%	O
+and	O
+60	O
+%	O
+after	O
+MPTP	O
+treatment	O
+,	O
+respectively	O
+.	O
+
+Instead	O
+,	O
+the	O
+results	O
+support	O
+the	O
+idea	O
+that	O
+Pc	B-GENE
+group	I-GENE
+products	I-GENE
+provide	O
+stable	O
+memory	O
+or	O
+imprinting	O
+of	O
+boundaries	O
+which	O
+are	O
+initially	O
+specified	O
+by	O
+gap	O
+and	O
+pair	O
+-	O
+rule	O
+regulators	O
+.	O
+
+To	O
+investigate	O
+the	O
+regulation	O
+of	O
+expression	O
+of	O
+the	O
+human	B-GENE
+mdr1	I-GENE
+gene	I-GENE
+,	O
+the	O
+response	O
+of	O
+the	O
+mdr1	B-GENE
+promoter	I-GENE
+to	O
+signals	O
+involved	O
+in	O
+cell	O
+proliferation	O
+was	O
+examined	O
+.	O
+
+Tobacco	O
+mosaic	O
+virus	O
+-	O
+infected	O
+tobacco	O
+(	O
+Nicotiana	O
+tabacum	O
+var	O
+.	O
+
+Through	O
+a	O
+stretch	O
+of	O
+56	O
+amino	O
+acids	O
+,	O
+constituting	O
+the	O
+MADS	B-GENE
+domain	I-GENE
+,	O
+the	O
+two	O
+proteins	O
+are	O
+identical	O
+except	O
+for	O
+two	O
+conservative	O
+amino	O
+acid	O
+substitutions	O
+.	O
+
+Isolation	O
+and	O
+characterization	O
+of	O
+SRF	B-GENE
+accessory	I-GENE
+proteins	I-GENE
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+:	O
+(	O
+a	O
+)	O
+proSRIF	B-GENE
+cleavage	O
+is	O
+initiated	O
+in	O
+the	O
+TGN	O
+,	O
+and	O
+(	O
+b	O
+)	O
+this	O
+reaction	O
+requires	O
+an	O
+acidic	O
+pH	O
+which	O
+is	O
+facilitated	O
+by	O
+a	O
+Golgi	B-GENE
+-	I-GENE
+associated	I-GENE
+vacuolar	I-GENE
+-	I-GENE
+type	I-GENE
+ATPase	I-GENE
+.	O
+
+Clinical	O
+aspects	O
+of	O
+early	O
+increase	O
+in	O
+serum	O
+gamma	B-GENE
+-	I-GENE
+glutamyl	I-GENE
+transferase	I-GENE
+in	O
+cerebral	O
+infarction	O
+.	O
+
+In	O
+the	O
+3	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+27	B-GENE
+kDa	I-GENE
+zein	I-GENE
+gene	I-GENE
+,	O
+several	O
+AATAAA	O
+-	O
+like	O
+sequences	O
+and	O
+a	O
+sequence	O
+resembling	O
+the	O
+mammalian	O
+GT	O
+-	O
+rich	O
+sequence	O
+are	O
+present	O
+around	O
+the	O
+polyadenylation	O
+sites	O
+.	O
+
+The	O
+indoor	O
+radon	O
+concentration	O
+in	O
+the	O
+summer	O
+(	O
+1990	O
+)	O
+period	O
+ranged	O
+between	O
+8	O
+and	O
+81	O
+Bq	O
+m	O
+-	O
+3	O
+,	O
+while	O
+in	O
+the	O
+winter	O
+(	O
+1989	O
+-	O
+1990	O
+)	O
+it	O
+ranged	O
+between	O
+20	O
+and	O
+143	O
+Bq	O
+m	O
+-	O
+3	O
+for	O
+the	O
+first	O
+year	O
+of	O
+measurements	O
+or	O
+between	O
+8	O
+and	O
+92	O
+Bq	O
+m	O
+-	O
+3	O
+in	O
+the	O
+summer	O
+(	O
+1991	O
+)	O
+period	O
+and	O
+between	O
+12	O
+and	O
+119	O
+Bq	O
+m	O
+-	O
+3	O
+in	O
+the	O
+winter	O
+(	O
+1990	O
+-	O
+1991	O
+)	O
+for	O
+the	O
+second	O
+year	O
+of	O
+measurements	O
+.	O
+
+DtxR	B-GENE
+is	O
+an	O
+iron	O
+-	O
+dependent	O
+sequence	O
+-	O
+specific	O
+DNA	O
+-	O
+binding	O
+protein	O
+that	O
+binds	O
+to	O
+the	O
+tox	B-GENE
+operator	I-GENE
+,	O
+an	O
+inverted	O
+-	O
+repeat	O
+nucleotide	O
+sequence	O
+located	O
+upstream	O
+from	O
+the	O
+diphtheria	B-GENE
+toxin	I-GENE
+gene	I-GENE
+.	O
+
+Vasopressin	B-GENE
+(	O
+AVP	B-GENE
+)	O
+,	O
+the	O
+antidiuretic	O
+hormone	O
+,	O
+is	O
+a	O
+cyclic	O
+nonapeptide	O
+that	O
+acts	O
+through	O
+binding	O
+to	O
+G	B-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+specific	I-GENE
+membrane	I-GENE
+receptors	I-GENE
+pharmacologically	O
+divided	O
+into	O
+three	O
+subtypes	O
+(	O
+V1a	B-GENE
+,	O
+V1b	B-GENE
+,	O
+and	O
+V2	B-GENE
+)	O
+linked	O
+to	O
+distinct	O
+second	O
+messengers	O
+.	O
+
+These	O
+results	O
+confirmed	O
+that	O
+cleavage	O
+of	O
+the	O
+leader	O
+peptide	O
+is	O
+the	O
+last	O
+step	O
+in	O
+nisin	B-GENE
+maturation	O
+and	O
+is	O
+necessary	O
+to	O
+generate	O
+a	O
+biologically	O
+active	O
+peptide	O
+.	O
+
+When	O
+the	O
+promoter	O
+region	O
+was	O
+linked	O
+with	O
+a	O
+heterologous	O
+reporter	O
+gene	O
+,	O
+we	O
+found	O
+that	O
+the	O
+promoter	O
+region	O
+is	O
+inducible	O
+by	O
+both	O
+interferons	B-GENE
+(	O
+interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	I-GENE
+-	I-GENE
+gamma	I-GENE
+)	O
+and	O
+interferon	B-GENE
+regulatory	I-GENE
+factor	I-GENE
+1	I-GENE
+.	O
+
+Anti	B-GENE
+-	I-GENE
+B	I-GENE
+.	I-GENE
+burgdorferi	I-GENE
+,	O
+anti	B-GENE
+-	I-GENE
+B	I-GENE
+.	I-GENE
+turicatae	I-GENE
+and	O
+anti	B-GENE
+-	I-GENE
+B	I-GENE
+.	I-GENE
+parkeri	I-GENE
+antibodies	I-GENE
+,	O
+tested	O
+by	O
+the	O
+indirect	O
+immunofluorescent	O
+assay	O
+(	O
+IFA	O
+)	O
+,	O
+were	O
+detected	O
+in	O
+10	O
+.	O
+8	O
+,	O
+16	O
+.	O
+1	O
+and	O
+8	O
+.	O
+2	O
+%	O
+of	O
+the	O
+serum	O
+samples	O
+tested	O
+,	O
+and	O
+confirmed	O
+by	O
+IFA	O
+-	O
+ABS	O
+in	O
+1	O
+.	O
+3	O
+,	O
+1	O
+.	O
+3	O
+and	O
+1	O
+.	O
+0	O
+%	O
+,	O
+respectively	O
+.	O
+
+The	O
+approach	O
+derives	O
+from	O
+a	O
+recently	O
+described	O
+strategy	O
+for	O
+making	O
+recombinants	O
+from	O
+five	O
+overlapping	O
+EBV	O
+cosmid	O
+-	O
+cloned	O
+DNAs	O
+(	O
+B	O
+.	O
+
+Evaluation	O
+of	O
+desmopressin	O
+for	O
+dental	O
+extractions	O
+in	O
+patients	O
+with	O
+hemostatic	O
+disorders	O
+.	O
+
+Comparative	O
+analysis	O
+with	O
+an	O
+antiandrogen	O
+niftolid	O
+and	O
+synthetic	B-GENE
+GnRH	I-GENE
+was	O
+carried	O
+out	O
+in	O
+22	O
+normal	O
+subjects	O
+,	O
+14	O
+patients	O
+with	O
+primary	O
+and	O
+20	O
+ones	O
+with	O
+secondary	O
+hypogonadism	O
+,	O
+and	O
+in	O
+5	O
+patients	O
+with	O
+clinical	O
+signs	O
+of	O
+gonadal	O
+insufficiency	O
+and	O
+obscure	O
+diagnosis	O
+in	O
+order	O
+to	O
+elucidate	O
+the	O
+pituitary	B-GENE
+gonadotropin	I-GENE
+reserves	O
+.	O
+
+The	O
+cis	O
+-	O
+acting	O
+regulatory	O
+properties	O
+of	O
+an	O
+872	O
+bp	O
+promoter	O
+fragment	O
+of	O
+a	O
+B	O
+.	O
+napus	O
+oleosin	B-GENE
+gene	I-GENE
+were	O
+examined	O
+by	O
+analysis	O
+of	O
+beta	B-GENE
+-	I-GENE
+glucuronidase	I-GENE
+(	O
+GUS	B-GENE
+)	O
+expression	O
+in	O
+transgenic	O
+tobacco	O
+plants	O
+containing	O
+an	O
+oleosin	B-GENE
+promoter	I-GENE
+-	O
+GUS	B-GENE
+transcriptional	O
+fusion	O
+.	O
+
+This	O
+indicates	O
+that	O
+the	O
+mechanism	O
+by	O
+which	O
+CX	O
+blocks	O
+rapid	O
+degradation	O
+of	O
+tubulin	B-GENE
+mRNA	I-GENE
+in	O
+vivo	O
+is	O
+not	O
+simply	O
+by	O
+preventing	O
+its	O
+translation	O
+and	O
+suggests	O
+the	O
+involvement	O
+of	O
+an	O
+altered	O
+trans	O
+-	O
+factor	O
+.	O
+
+Increasing	O
+the	O
+extracellular	O
+calcium	O
+concentration	O
+enhanced	O
+detrusor	O
+contractility	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+in	O
+both	O
+control	O
+and	O
+obstructed	O
+bladders	O
+.	O
+
+Structural	O
+organization	O
+of	O
+the	O
+gene	O
+encoding	O
+the	O
+human	B-GENE
+lipocalin	I-GENE
+tear	I-GENE
+prealbumin	I-GENE
+and	O
+synthesis	O
+of	O
+the	O
+recombinant	O
+protein	O
+in	O
+Escherichia	O
+coli	O
+.	O
+
+The	O
+sequence	O
+has	O
+a	O
+1092	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+encoding	O
+a	O
+protein	O
+of	O
+364	O
+amino	O
+acids	O
+.	O
+
+The	O
+gene	O
+organization	O
+of	O
+CRSV	B-GENE
+RNA	I-GENE
+-	I-GENE
+1	I-GENE
+is	O
+similar	O
+to	O
+those	O
+of	O
+red	O
+clover	O
+necrotic	O
+mosaic	O
+(	O
+RCNMV	O
+)	O
+and	O
+sweet	O
+clover	O
+necrotic	O
+mosaic	O
+(	O
+SCNMV	O
+)	O
+dianthoviruses	O
+with	O
+the	O
+exception	O
+that	O
+CRSV	B-GENE
+RNA	I-GENE
+-	I-GENE
+1	I-GENE
+contains	O
+the	O
+additional	O
+3	O
+'	O
+-	O
+terminal	O
+ORF	O
+.	O
+
+We	O
+have	O
+previously	O
+shown	O
+that	O
+LBP	B-GENE
+-	I-GENE
+1	I-GENE
+represses	O
+HIV	O
+-	O
+1	O
+transcription	O
+by	O
+inhibiting	O
+the	O
+binding	O
+of	O
+TFIID	B-GENE
+to	O
+the	O
+TATA	O
+box	O
+.	O
+
+These	O
+results	O
+illustrate	O
+an	O
+important	O
+role	O
+for	O
+La	B-GENE
+in	O
+RNA	O
+production	O
+by	O
+demonstrating	O
+its	O
+ability	O
+to	O
+clear	O
+the	O
+termination	O
+sites	O
+of	O
+class	O
+III	O
+templates	O
+,	O
+thereby	O
+promoting	O
+efficient	O
+use	O
+of	O
+transcription	O
+complexes	O
+by	O
+pol	B-GENE
+III	I-GENE
+.	O
+
+The	O
+films	O
+were	O
+analyzed	O
+using	O
+a	O
+scanning	O
+helium	O
+-	O
+neon	O
+laser	O
+densitometer	O
+with	O
+a	O
+small	O
+aperture	O
+of	O
+5	O
+-	O
+10	O
+microns	O
+.	O
+
+The	O
+GafChromic	O
+method	O
+has	O
+proven	O
+to	O
+be	O
+an	O
+accurate	O
+and	O
+rapid	O
+method	O
+of	O
+analysis	O
+and	O
+could	O
+be	O
+easily	O
+incorporated	O
+into	O
+a	O
+quality	O
+assurance	O
+program	O
+.	O
+
+Viral	O
+genomic	O
+RNA	O
+for	O
+these	O
+reactions	O
+was	O
+obtained	O
+directly	O
+from	O
+fecal	O
+specimens	O
+of	O
+infected	O
+infant	O
+rats	O
+.	O
+
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+was	O
+present	O
+in	O
+equivalent	O
+levels	O
+in	O
+both	O
+erythroid	O
+cell	O
+lines	O
+,	O
+but	O
+at	O
+a	O
+low	O
+level	O
+in	O
+FDC	O
+-	O
+P1	O
+cells	O
+.	O
+
+Tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+alpha	I-GENE
+)	O
+is	O
+one	O
+of	O
+several	O
+autocrine	O
+/	O
+paracrine	O
+factors	O
+known	O
+to	O
+exert	O
+potent	O
+inhibitory	O
+effects	O
+on	O
+bone	O
+.	O
+
+We	O
+have	O
+investigated	O
+the	O
+role	O
+of	O
+cellular	B-GENE
+p21ras	I-GENE
+protein	I-GENE
+in	O
+insulin	B-GENE
+and	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+I	I-GENE
+(	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+)	O
+signaling	O
+pathways	O
+.	O
+
+The	O
+lack	O
+of	O
+the	O
+C2	B-GENE
+domain	O
+of	O
+the	O
+Ca	B-GENE
+(	I-GENE
+2	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+dependent	I-GENE
+PKCs	I-GENE
+and	O
+the	O
+presence	O
+of	O
+a	O
+unique	O
+NH2	O
+-	O
+terminal	O
+sequence	O
+with	O
+a	O
+potential	O
+signal	O
+peptide	O
+and	O
+a	O
+transmembrane	O
+domain	O
+suggest	O
+that	O
+PKC	B-GENE
+mu	I-GENE
+is	O
+a	O
+novel	O
+member	O
+of	O
+the	O
+subgroup	O
+of	O
+atypical	O
+PKCs	B-GENE
+.	O
+
+Moreover	O
+,	O
+we	O
+observed	O
+that	O
+the	O
+function	O
+of	O
+T3R	B-GENE
+-	O
+RXR	B-GENE
+heterodimers	O
+on	O
+response	O
+elements	O
+composed	O
+of	O
+two	O
+half	O
+-	O
+sites	O
+in	O
+a	O
+directly	O
+repeated	O
+orientation	O
+spaced	O
+by	O
+4	O
+nucleotides	O
+is	O
+determined	O
+in	O
+major	O
+parts	O
+by	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+sequence	O
+of	O
+the	O
+upstream	O
+half	O
+-	O
+site	O
+.	O
+
+However	O
+,	O
+three	O
+Hm1	B-GENE
+mutants	I-GENE
+that	O
+were	O
+moderately	O
+deficient	O
+in	O
+stimulating	O
+PI	O
+turnover	O
+displayed	O
+normal	O
+sequestration	O
+,	O
+suggesting	O
+distinct	O
+mechanisms	O
+.	O
+
+Furthermore	O
+,	O
+in	O
+vitro	O
+decay	O
+reaction	O
+mixtures	O
+supplemented	O
+with	O
+the	O
+20	O
+-	O
+nt	O
+sense	O
+RNA	O
+transcript	O
+resulted	O
+in	O
+stabilization	O
+of	O
+R2	B-GENE
+message	I-GENE
+.	O
+
+Deletion	O
+analyses	O
+of	O
+the	O
+pCD41	B-GENE
+ORF	I-GENE
+-	I-GENE
+A	I-GENE
+and	O
+the	O
+use	O
+of	O
+promoter	O
+constructs	O
+further	O
+mapped	O
+an	O
+internal	O
+functional	O
+promoter	O
+within	O
+the	O
+pCD41	B-GENE
+sequence	I-GENE
+that	O
+can	O
+direct	O
+the	O
+synthesis	O
+of	O
+the	O
+trans	O
+-	O
+activating	O
+protein	O
+.	O
+
+The	O
+inferred	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+cyanobacterial	B-GENE
+HemB	I-GENE
+protein	I-GENE
+indicates	O
+a	O
+significant	O
+difference	O
+in	O
+the	O
+metal	O
+cofactor	O
+requirement	O
+from	O
+the	O
+higher	O
+-	O
+plant	O
+enzymes	O
+,	O
+which	O
+was	O
+confirmed	O
+by	O
+overexpression	O
+and	O
+biochemical	O
+analysis	O
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+In	O
+25	O
+open	O
+-	O
+chest	O
+,	O
+anesthetized	O
+dogs	O
+,	O
+progressive	O
+circumflex	O
+artery	O
+stenosis	O
+led	O
+to	O
+a	O
+concordant	O
+decrease	O
+of	O
+circumflex	O
+artery	O
+resting	O
+and	O
+hyperemic	O
+flow	O
+,	O
+coronary	O
+flow	O
+reserve	O
+,	O
+and	O
+inverse	O
+angiographic	O
+mean	O
+transit	O
+time	O
+Tmicro	O
+-	O
+1	O
+(	O
+P	O
+<	O
+.	O
+01	O
+)	O
+.	O
+
+However	O
+,	O
+a	O
+correlation	O
+was	O
+observed	O
+between	O
+SF	O
+levels	O
+of	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+with	O
+those	O
+of	O
+lactate	O
+,	O
+LDH	B-GENE
+,	O
+beta	B-GENE
+2	I-GENE
+-	I-GENE
+microglobulin	I-GENE
+and	O
+glucose	O
+.	O
+
+Sodium	O
+-	O
+taurocholate	O
+-	O
+induced	O
+acute	O
+necrotizing	O
+pancreatitis	O
+does	O
+not	O
+affect	O
+jejunal	O
+oxygenation	O
+in	O
+pigs	O
+.	O
+
+Although	O
+inactive	O
+in	O
+cells	O
+under	O
+normal	O
+conditions	O
+,	O
+the	O
+CHOP	B-GENE
+gene	I-GENE
+is	O
+markedly	O
+induced	O
+by	O
+a	O
+variety	O
+of	O
+cellular	O
+stresses	O
+,	O
+including	O
+nutrient	O
+deprivation	O
+and	O
+metabolic	O
+perturbations	O
+.	O
+
+The	O
+ipiO	B-GENE
+genes	I-GENE
+code	O
+for	O
+two	O
+almost	O
+identical	O
+152	O
+-	O
+aa	O
+proteins	O
+which	O
+do	O
+not	O
+have	O
+any	O
+homology	O
+with	O
+sequences	O
+present	O
+in	O
+data	O
+libraries	O
+.	O
+
+Sterol	O
+analysis	O
+of	O
+the	O
+disrupted	O
+mutant	O
+demonstrated	O
+the	O
+accumulation	O
+of	O
+ignosterol	O
+,	O
+indicating	O
+a	O
+loss	O
+of	O
+Erg24p	B-GENE
+activity	O
+.	O
+
+In	O
+these	O
+experiments	O
+we	O
+begin	O
+to	O
+study	O
+the	O
+potential	O
+functions	O
+of	O
+the	O
+alpha	B-GENE
+7	I-GENE
+cytoplasmic	I-GENE
+domain	I-GENE
+by	O
+analyzing	O
+homologies	O
+between	O
+the	O
+rat	O
+and	O
+human	O
+sequences	O
+,	O
+by	O
+immunologic	O
+studies	O
+using	O
+an	O
+anti	O
+-	O
+cytoplasmic	O
+domain	O
+antiserum	O
+,	O
+and	O
+by	O
+identifying	O
+two	O
+alternate	O
+forms	O
+.	O
+
+The	O
+alpha	O
+7A	O
+form	O
+RNA	O
+contains	O
+an	O
+additional	O
+113	O
+nucleotides	O
+compared	O
+to	O
+the	O
+B	O
+form	O
+,	O
+and	O
+a	O
+common	O
+coding	O
+region	O
+in	O
+the	O
+A	O
+and	O
+B	O
+form	O
+RNAs	O
+is	O
+used	O
+in	O
+alternate	O
+reading	O
+frames	O
+.	O
+
+In	O
+order	O
+to	O
+evaluate	O
+the	O
+function	O
+of	O
+the	O
+hypothalamic	O
+-	O
+pituitary	O
+-	O
+thyroid	O
+(	O
+HPT	O
+)	O
+-	O
+axis	O
+in	O
+unipolar	O
+depression	O
+,	O
+the	O
+authors	O
+measured	O
+basal	O
+0800h	O
+plasma	O
+levels	O
+of	O
+free	O
+thyroxine	O
+(	O
+FT4	O
+)	O
+,	O
+free	O
+triiodothyronine	O
+(	O
+FT3	O
+)	O
+,	O
+and	O
+thyroid	B-GENE
+stimulating	I-GENE
+hormone	I-GENE
+(	O
+TSH	B-GENE
+)	O
+by	O
+means	O
+of	O
+the	O
+new	O
+,	O
+ultrasensitive	O
+assays	O
+(	O
+TSH	O
+-	O
+IRMA	O
+)	O
+in	O
+69	O
+healthy	O
+controls	O
+,	O
+62	O
+minor	O
+,	O
+101	O
+simple	O
+major	O
+,	O
+and	O
+57	O
+melancholic	O
+depressed	O
+subjects	O
+.	O
+
+CRS	B-GENE
+function	O
+in	O
+a	O
+5	O
+'	O
+LTR	O
+-	O
+linked	O
+gene	O
+expression	O
+assay	O
+correlates	O
+with	O
+the	O
+ability	O
+of	O
+both	O
+p60CRS	B-GENE
+and	O
+p40CRS	B-GENE
+to	O
+interact	O
+with	O
+5	O
+'	O
+LTR	O
+RNA	O
+in	O
+vitro	O
+.	O
+
+Serial	O
+levels	O
+of	O
+troponin	B-GENE
+T	I-GENE
+and	O
+the	O
+activity	O
+of	O
+CK	B-GENE
+-	I-GENE
+MB	I-GENE
+were	O
+measured	O
+6	O
+,	O
+12	O
+,	O
+24	O
+and	O
+48	O
+h	O
+after	O
+aortic	O
+unclamping	O
+.	O
+
+Regionalization	O
+of	O
+drug	O
+delivery	O
+is	O
+a	O
+potential	O
+method	O
+to	O
+avoid	O
+this	O
+problem	O
+.	O
+
+The	O
+epidemic	O
+occurred	O
+in	O
+a	O
+group	O
+of	O
+26	O
+community	O
+members	O
+(	O
+23	O
+men	O
+and	O
+3	O
+women	O
+,	O
+mean	O
+age	O
+,	O
+28	O
+.	O
+9	O
+-	O
+-	O
+3	O
+years	O
+)	O
+living	O
+and	O
+working	O
+together	O
+,	O
+who	O
+underwent	O
+acute	O
+and	O
+convalescent	O
+serologic	O
+tests	O
+for	O
+Mycoplasma	O
+pneumoniae	O
+,	O
+Legionella	O
+pneumophila	O
+,	O
+cytomegalovirus	O
+,	O
+adenovirus	O
+,	O
+Coxiella	O
+burnetii	O
+,	O
+and	O
+Chlamydia	O
+pneumoniae	O
+.	O
+
+MEK	B-GENE
+itself	O
+is	O
+activated	O
+via	O
+serine	O
+phosphorylation	O
+by	O
+upstream	B-GENE
+activator	I-GENE
+kinases	I-GENE
+,	O
+including	O
+c	B-GENE
+-	I-GENE
+raf	I-GENE
+,	O
+mos	B-GENE
+and	O
+MEK	B-GENE
+kinase	I-GENE
+.	O
+
+Members	O
+of	O
+SVA	B-GENE
+are	O
+also	O
+present	O
+in	O
+the	O
+complement	B-GENE
+C2	I-GENE
+gene	I-GENE
+located	O
+about	O
+20	O
+kilobases	O
+upstream	O
+of	O
+RP1	B-GENE
+in	O
+the	O
+HLA	B-GENE
+and	O
+in	O
+the	O
+cytochrome	B-GENE
+CYP1A1	I-GENE
+gene	I-GENE
+.	O
+
+European	O
+Community	O
+Huntington	O
+'	O
+s	O
+Disease	O
+Collaborative	O
+Study	O
+Group	O
+.	O
+
+The	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+and	O
+skeletal	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+gene	I-GENE
+promoters	I-GENE
+contain	O
+YY1	B-GENE
+binding	I-GENE
+sites	I-GENE
+thought	O
+to	O
+act	O
+either	O
+as	O
+positive	O
+or	O
+negative	O
+cis	O
+-	O
+acting	O
+elements	O
+.	O
+
+MSSP	B-GENE
+-	I-GENE
+1	I-GENE
+produced	O
+in	O
+E	O
+.	O
+coli	O
+as	O
+a	O
+fusion	O
+protein	O
+with	O
+GST	B-GENE
+specifically	O
+interacted	O
+with	O
+single	O
+-	O
+stranded	O
+TCTTAT	O
+(	O
+plus	O
+myc	B-GENE
+(	O
+H	O
+-	O
+P	O
+)	O
+21	O
+)	O
+and	O
+ACT	O
+-	O
+ATT	O
+(	O
+in	O
+minus	O
+myc	B-GENE
+(	O
+H	O
+-	O
+P	O
+)	O
+21	O
+)	O
+,	O
+the	O
+consensus	O
+of	O
+which	O
+can	O
+be	O
+referred	O
+to	O
+as	O
+A	O
+/	O
+TCTA	O
+/	O
+TA	O
+/	O
+TT	O
+.	O
+
+Within	O
+12	O
+hours	O
+after	O
+MR	O
+tomography	O
+the	O
+patients	O
+were	O
+surgically	O
+explored	O
+,	O
+biopsied	O
+and	O
+if	O
+necessary	O
+orchiectomised	O
+.	O
+
+Varieties	O
+of	O
+envious	O
+experience	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+both	O
+the	O
+amino	O
+and	O
+carboxy	O
+termini	O
+of	O
+the	O
+NS1	B-GENE
+protein	I-GENE
+molecule	I-GENE
+and	O
+the	O
+cysteines	O
+at	O
+residues	O
+337	O
+and	O
+340	O
+are	O
+essential	O
+for	O
+tubule	O
+formation	O
+.	O
+
+The	O
+3	O
+'	O
+UTR	O
+has	O
+several	O
+stable	O
+hairpins	O
+that	O
+are	O
+flanked	O
+by	O
+single	O
+-	O
+stranded	O
+(	O
+A	O
+/	O
+U	O
+)	O
+UGC	O
+sequences	O
+.	O
+
+Moreover	O
+,	O
+the	O
+major	O
+site	O
+of	O
+transcriptional	O
+initiation	O
+,	O
+which	O
+was	O
+localized	O
+by	O
+primer	O
+extension	O
+250	O
+bp	O
+upstream	O
+of	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+cDNA	I-GENE
+clone	I-GENE
+,	O
+was	O
+shown	O
+to	O
+be	O
+identical	O
+in	O
+normal	O
+cells	O
+and	O
+tumors	O
+carrying	O
+a	O
+provirus	O
+in	O
+the	O
+Tpl	B-GENE
+-	I-GENE
+1	I-GENE
+locus	I-GENE
+.	O
+
+Specifically	O
+,	O
+by	O
+oligonucleotide	O
+-	O
+directed	O
+site	O
+-	O
+specific	O
+mutagenesis	O
+,	O
+we	O
+demonstrate	O
+that	O
+of	O
+10	O
+cysteine	O
+residues	O
+in	O
+the	O
+ORF4	O
+polypeptide	O
+,	O
+only	O
+C	O
+-	O
+421	O
+and	O
+C	O
+-	O
+426	O
+are	O
+essential	O
+for	O
+transactivator	O
+function	O
+and	O
+suggest	O
+that	O
+these	O
+cysteine	O
+residues	O
+may	O
+participate	O
+in	O
+critical	O
+protein	O
+-	O
+protein	O
+interactions	O
+rather	O
+than	O
+protein	O
+-	O
+nucleic	O
+acid	O
+interactions	O
+to	O
+mediate	O
+ORF4	O
+inducibility	O
+.	O
+
+To	O
+search	O
+for	O
+genes	O
+that	O
+interact	O
+with	O
+the	O
+SLK1	B-GENE
+-	O
+SLT2	B-GENE
+pathway	O
+,	O
+a	O
+synthetic	O
+lethal	O
+suppression	O
+screen	O
+was	O
+carried	O
+out	O
+.	O
+
+Genetic	O
+and	O
+phenotypic	O
+analysis	O
+indicates	O
+that	O
+NHP6A	B-GENE
+and	O
+NHP6B	B-GENE
+function	O
+downstream	O
+of	O
+SLT2	B-GENE
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+present	O
+two	O
+lines	O
+of	O
+evidence	O
+that	O
+all	O
+ribosomes	O
+which	O
+synthesize	O
+GCN4	B-GENE
+have	O
+previously	O
+translated	O
+uORF1	O
+,	O
+resumed	O
+scanning	O
+,	O
+and	O
+reinitiated	O
+at	O
+the	O
+GCN4	B-GENE
+start	O
+site	O
+.	O
+
+Identical	O
+components	O
+of	O
+yeast	O
+transcription	B-GENE
+factor	I-GENE
+IIIB	I-GENE
+are	O
+required	O
+and	O
+sufficient	O
+for	O
+transcription	O
+of	O
+TATA	O
+box	O
+-	O
+containing	O
+and	O
+TATA	O
+-	O
+less	O
+genes	O
+.	O
+
+Concordantly	O
+,	O
+it	O
+was	O
+shown	O
+that	O
+the	O
+dnHLH	B-GENE
+protein	I-GENE
+Id1	B-GENE
+inhibits	O
+differentiation	O
+of	O
+muscle	O
+and	O
+myeloid	O
+cells	O
+in	O
+vitro	O
+.	O
+
+RNP1	B-GENE
+,	O
+a	O
+new	O
+ribonucleoprotein	O
+gene	O
+of	O
+the	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Crohn	O
+'	O
+s	O
+disease	O
+in	O
+prolonged	O
+remission	O
+:	O
+should	O
+one	O
+augment	O
+protein	O
+-	O
+calorie	O
+intake	O
+as	O
+compared	O
+to	O
+healthy	O
+subjects	O
+?	O
+]	O
+The	O
+aim	O
+of	O
+our	O
+two	O
+year	O
+prospective	O
+study	O
+was	O
+to	O
+evaluate	O
+whether	O
+adult	O
+Crohn	O
+'	O
+s	O
+disease	O
+patients	O
+in	O
+prolonged	O
+remission	O
+(	O
+CDAI	O
+<	O
+150	O
+)	O
+,	O
+in	O
+order	O
+to	O
+maintain	O
+their	O
+body	O
+weight	O
+as	O
+close	O
+as	O
+possible	O
+to	O
+the	O
+ideal	O
+one	O
+,	O
+need	O
+a	O
+protein	O
+-	O
+calorie	O
+intake	O
+higher	O
+than	O
+the	O
+predicted	O
+one	O
+and	O
+that	O
+of	O
+healthy	O
+controls	O
+.	O
+
+To	O
+achieve	O
+complete	O
+dissection	O
+of	O
+the	O
+anterior	O
+vitreous	O
+,	O
+we	O
+remove	O
+even	O
+a	O
+clear	O
+lens	O
+during	O
+the	O
+first	O
+surgical	O
+intervention	O
+in	O
+selected	O
+cases	O
+.	O
+
+Restoration	O
+of	O
+opponens	O
+function	O
+with	O
+transplantation	O
+of	O
+free	O
+composites	O
+dorsal	O
+pedal	O
+skin	O
+flap	O
+containing	O
+m	O
+.	O
+extensor	O
+hallucis	O
+brevis	O
+
+Neither	O
+ethanol	O
+regimen	O
+impaired	O
+spontaneous	O
+alternation	O
+,	O
+but	O
+the	O
+4	O
+g	O
+ethanol	O
+.	O
+kg	O
+-	O
+1	O
+x	O
+day	O
+-	O
+1	O
+regimen	O
+increased	O
+the	O
+percent	O
+completed	O
+trials	O
+.	O
+
+The	O
+mean	O
+(	O
++	O
+/	O
+-	O
+sd	O
+)	O
+intra	O
+-	O
+vesicular	O
+pressure	O
+(	O
+IVP	O
+)	O
+and	O
+maximal	O
+urethral	O
+closure	O
+pressures	O
+(	O
+MUCP	O
+)	O
+were	O
+10	O
+.	O
+3	O
+(	O
++	O
+/	O
+-	O
+1	O
+.	O
+7	O
+)	O
+and	O
+129	O
+.	O
+8	O
+(	O
++	O
+/	O
+-	O
+19	O
+.	O
+6	O
+)	O
+cmH2O	O
+,	O
+respectively	O
+,	O
+and	O
+the	O
+ratio	O
+between	O
+MUCP	O
+and	O
+IVP	O
+was	O
+13	O
+.	O
+2	O
+(	O
++	O
+/	O
+-	O
+2	O
+.	O
+5	O
+)	O
+.	O
+
+Several	O
+highly	O
+conserved	O
+regions	O
+were	O
+identified	O
+at	O
+the	O
+near	O
+N	O
+terminus	O
+,	O
+middle	O
+and	O
+C	O
+terminus	O
+.	O
+
+Thioredoxin	B-GENE
+(	O
+TR	B-GENE
+)	O
+is	O
+a	O
+small	O
+ubiquitous	O
+dithiol	B-GENE
+-	I-GENE
+reductase	I-GENE
+enzyme	I-GENE
+first	O
+identified	O
+in	O
+bacteria	O
+and	O
+plants	O
+.	O
+
+The	O
+mutation	O
+within	O
+the	O
+asgB480	B-GENE
+allele	I-GENE
+was	O
+identified	O
+as	O
+an	O
+A	O
+-	O
+to	O
+-	O
+G	O
+transition	O
+that	O
+results	O
+in	O
+a	O
+threonine	O
+-	O
+to	O
+-	O
+alanine	O
+substitution	O
+in	O
+the	O
+predicted	O
+protein	O
+product	O
+.	O
+
+The	O
+cysteine	O
+-	O
+rich	O
+region	O
+of	O
+raf	B-GENE
+-	I-GENE
+1	I-GENE
+kinase	I-GENE
+contains	O
+zinc	O
+,	O
+translocates	O
+to	O
+liposomes	O
+,	O
+and	O
+is	O
+adjacent	O
+to	O
+a	O
+segment	O
+that	O
+binds	O
+GTP	B-GENE
+-	I-GENE
+ras	I-GENE
+.	O
+
+Kinetic	O
+coupling	O
+and	O
+requirement	O
+for	O
+ATP	O
+hydrolysis	O
+.	O
+
+ATP	O
+by	O
+itself	O
+also	O
+reduced	O
+polypeptide	O
+binding	O
+to	O
+Ssb1	B-GENE
+/	I-GENE
+2p	I-GENE
+to	O
+a	O
+level	O
+that	O
+was	O
+intermediate	O
+between	O
+that	O
+observed	O
+for	O
+the	O
+Ssa	B-GENE
+Hsp70	B-GENE
+proteins	I-GENE
+tested	O
+and	O
+BiP	B-GENE
+and	O
+DnaK	B-GENE
+.	O
+
+Digestion	O
+of	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+with	O
+endoprotease	B-GENE
+Asp	I-GENE
+-	I-GENE
+N	I-GENE
+produced	O
+a	O
+domain	O
+smaller	O
+than	O
+the	O
+TCD	B-GENE
+(	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+bZIP	I-GENE
+domains	I-GENE
+(	O
+NFBD	B-GENE
+)	O
+(	O
+272	O
+-	O
+345	O
+)	O
+)	O
+,	O
+a	O
+domain	O
+identified	O
+either	O
+in	O
+the	O
+absence	O
+or	O
+the	O
+presence	O
+of	O
+DNA	O
+.	O
+
+Signaling	O
+by	O
+tyrosine	B-GENE
+kinases	I-GENE
+involves	O
+direct	O
+associations	O
+between	O
+proteins	O
+with	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+(	O
+SH2	B-GENE
+)	O
+domains	O
+and	O
+sites	O
+of	O
+tyrosine	O
+phosphorylation	O
+.	O
+
+Rather	O
+,	O
+complete	O
+skipping	O
+of	O
+exon	O
+V	O
+and	O
+subsequent	O
+joining	O
+of	O
+exon	O
+IV	O
+to	O
+exon	O
+VI	O
+caused	O
+a	O
+shift	O
+in	O
+the	O
+open	O
+reading	O
+frame	O
+,	O
+which	O
+remodeled	O
+GPHe	B-GENE
+(	I-GENE
+P2	I-GENE
+)	I-GENE
+with	O
+an	O
+elongated	O
+new	O
+hydrophobic	O
+sequence	O
+for	O
+membrane	O
+anchoring	O
+.	O
+
+The	O
+responses	O
+of	O
+the	O
+"	O
+stress	O
+hormones	O
+"	O
+cortisol	O
+,	O
+11	O
+-	O
+deoxycortisol	O
+,	O
+ACTH	B-GENE
+,	O
+vasopressin	B-GENE
+(	O
+AVP	B-GENE
+)	O
+,	O
+and	O
+corticotropin	B-GENE
+releasing	I-GENE
+factor	I-GENE
+(	O
+CRF	B-GENE
+)	O
+were	O
+studied	O
+in	O
+6	O
+normal	O
+males	O
+in	O
+response	O
+to	O
+acute	O
+cortisol	O
+deficiency	O
+induced	O
+by	O
+the	O
+11	B-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+hydroxylase	I-GENE
+inhibitor	O
+,	O
+metyrapone	O
+.	O
+
+Thus	O
+our	O
+observations	O
+establish	O
+a	O
+functional	O
+link	O
+between	O
+the	O
+PKC	B-GENE
+and	O
+retinoid	O
+pathways	O
+,	O
+which	O
+are	O
+generally	O
+considered	O
+to	O
+have	O
+antagonistic	O
+activities	O
+on	O
+differentiation	O
+processes	O
+.	O
+
+The	O
+colony	B-GENE
+-	I-GENE
+stimulating	I-GENE
+factors	I-GENE
+(	O
+CSFs	B-GENE
+)	O
+principally	O
+involved	O
+in	O
+the	O
+production	O
+of	O
+neutrophils	O
+and	O
+monocytes	O
+are	O
+granulocyte	B-GENE
+CSF	I-GENE
+,	O
+granulocyte	B-GENE
+-	I-GENE
+macrophage	I-GENE
+CSF	I-GENE
+,	O
+macrophage	B-GENE
+CSF	I-GENE
+,	O
+and	O
+interleukin	B-GENE
+3	I-GENE
+(	O
+sometimes	O
+called	O
+multi	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+.	O
+
+The	O
+degree	O
+of	O
+lung	O
+destruction	O
+,	O
+reflected	O
+by	O
+interstitial	O
+hemorrhage	O
+was	O
+assessed	O
+by	O
+measuring	O
+hemoglobin	B-GENE
+content	O
+in	O
+the	O
+fluid	O
+of	O
+the	O
+lavaged	O
+lungs	O
+.	O
+
+Expression	O
+plasmids	O
+harboring	O
+full	O
+-	O
+length	O
+or	O
+kinase	O
+domain	O
+of	O
+PKC	B-GENE
+alpha	I-GENE
+and	O
+PKC	B-GENE
+delta	I-GENE
+(	O
+PKC	B-GENE
+alpha	I-GENE
+K	I-GENE
+and	O
+PKC	B-GENE
+delta	I-GENE
+K	I-GENE
+)	O
+were	O
+constructed	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+both	O
+PKC	B-GENE
+alpha	I-GENE
+(	O
+calcium	O
+dependent	O
+)	O
+and	O
+PKC	B-GENE
+delta	I-GENE
+(	O
+calcium	O
+independent	O
+)	O
+may	O
+mediate	O
+the	O
+transcription	O
+of	O
+TPA	O
+-	O
+inducible	O
+genes	O
+through	O
+both	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+non	O
+-	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+sequences	O
+.	O
+
+With	O
+a	O
+cutoff	O
+level	O
+for	O
+TSST	B-GENE
+-	I-GENE
+1	I-GENE
+of	O
+less	O
+than	O
+100	O
+pg	O
+/	O
+ml	O
+,	O
+28	O
+samples	O
+obtained	O
+from	O
+12	O
+patients	O
+were	O
+positive	O
+for	O
+TSST	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Panlobular	O
+emphysema	O
+
+Since	O
+the	O
+ETS	B-GENE
+domain	I-GENE
+,	O
+which	O
+is	O
+localized	O
+in	O
+the	O
+carboxy	O
+terminal	O
+region	O
+of	O
+the	O
+encoded	O
+protein	O
+,	O
+is	O
+95	O
+%	O
+and	O
+96	O
+%	O
+identical	O
+to	O
+that	O
+of	O
+PEA3	B-GENE
+and	O
+ER81	B-GENE
+,	O
+respectively	O
+,	O
+we	O
+named	O
+this	O
+new	O
+member	O
+'	B-GENE
+Ets	I-GENE
+Related	I-GENE
+Molecule	I-GENE
+PEA3	I-GENE
+-	I-GENE
+like	I-GENE
+'	I-GENE
+(	O
+ERM	B-GENE
+)	O
+.	O
+
+Gel	O
+shift	O
+analysis	O
+indicates	O
+that	O
+the	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+ERM	I-GENE
+protein	I-GENE
+is	O
+able	O
+to	O
+bind	O
+specifically	O
+to	O
+an	O
+oligonucleotide	O
+containing	O
+the	O
+consensus	O
+nucleotide	O
+core	O
+sequence	O
+GGAA	O
+recognized	O
+by	O
+the	O
+Ets	B-GENE
+proteins	O
+.	O
+
+Effects	O
+of	O
+estradiol	O
+on	O
+worm	O
+burden	O
+and	O
+peripheral	O
+leukocytes	O
+in	O
+Parastrongylus	O
+malaysiensis	O
+-	O
+infected	O
+rats	O
+.	O
+
+Dotarizine	O
+produced	O
+arterial	O
+dilation	O
+in	O
+both	O
+systemic	O
+and	O
+pulmonary	O
+circulation	O
+:	O
+the	O
+total	O
+peripheral	O
+resistance	O
+dropped	O
+,	O
+and	O
+femoral	O
+artery	O
+flow	O
+rose	O
+;	O
+aortic	O
+and	O
+pulmonary	O
+artery	O
+mean	O
+and	O
+diastolic	O
+pressures	O
+declined	O
+,	O
+and	O
+systolic	O
+pressures	O
+remained	O
+almost	O
+stable	O
+.	O
+
+These	O
+issues	O
+include	O
+the	O
+use	O
+of	O
+LMWHs	O
+in	O
+patients	O
+with	O
+arterial	O
+thrombosis	O
+or	O
+myocardial	O
+infarction	O
+(	O
+e	O
+.	O
+g	O
+.	O
+in	O
+conjunction	O
+with	O
+thrombolytic	O
+treatment	O
+)	O
+,	O
+and	O
+in	O
+patients	O
+with	O
+pulmonary	O
+embolism	O
+.	O
+
+The	O
+usefulness	O
+of	O
+the	O
+lambda	O
+PG15	O
+and	O
+the	O
+lambda	O
+AD5	O
+cloning	O
+vectors	O
+was	O
+demonstrated	O
+by	O
+constructing	O
+large	O
+Neurospora	O
+crassa	O
+cDNA	O
+libraries	O
+.	O
+
+Endoscopic	O
+transthoracic	O
+sympathectomy	O
+as	O
+adjuvant	O
+treatment	O
+for	O
+critical	O
+upper	O
+-	O
+limb	O
+ischaemia	O
+.	O
+
+Sequence	O
+comparisons	O
+have	O
+shown	O
+that	O
+Aps1p	B-GENE
+is	O
+more	O
+similar	O
+to	O
+the	O
+sigma	O
+subunit	O
+of	O
+the	O
+Golgi	O
+-	O
+localized	O
+mammalian	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+complex	I-GENE
+than	O
+Aps2p	B-GENE
+,	O
+which	O
+is	O
+more	O
+related	O
+to	O
+the	O
+plasma	O
+membrane	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+sigma	I-GENE
+subunit	O
+.	O
+
+The	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+APS1	I-GENE
+gene	I-GENE
+encodes	O
+a	O
+homolog	O
+of	O
+the	O
+small	O
+subunit	O
+of	O
+the	O
+mammalian	B-GENE
+clathrin	I-GENE
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+complex	I-GENE
+:	O
+evidence	O
+for	O
+functional	O
+interaction	O
+with	O
+clathrin	B-GENE
+at	O
+the	O
+Golgi	O
+complex	O
+.	O
+
+These	O
+results	O
+are	O
+the	O
+first	O
+to	O
+demonstrate	O
+the	O
+structural	O
+organization	O
+of	O
+a	O
+vertebrate	O
+gene	O
+encoding	O
+an	O
+integral	O
+membrane	O
+protein	O
+of	O
+the	O
+nuclear	O
+envelope	O
+that	O
+may	O
+be	O
+a	O
+member	O
+of	O
+a	O
+family	O
+of	O
+polypeptides	O
+conserved	O
+in	O
+evolution	O
+.	O
+
+Biochemical	O
+characterization	O
+of	O
+valosin	B-GENE
+-	I-GENE
+containing	I-GENE
+protein	I-GENE
+,	O
+a	O
+protein	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+substrate	O
+in	O
+hematopoietic	O
+cells	O
+.	O
+
+The	O
+presence	O
+of	O
+the	O
+foreign	O
+gene	O
+was	O
+confirmed	O
+by	O
+Southern	O
+analysis	O
+.	O
+
+All	O
+patients	O
+with	O
+deterioriation	O
+in	O
+mental	O
+status	O
+showed	O
+a	O
+marked	O
+increase	O
+in	O
+liver	O
+enzymes	O
+(	O
+aspartate	B-GENE
+and	I-GENE
+alanine	I-GENE
+aminotransaminases	I-GENE
+)	O
+and	O
+severe	O
+coagulopathy	O
+.	O
+
+Functional	O
+postnatal	O
+development	O
+of	O
+the	O
+rat	O
+primary	O
+visual	O
+cortex	O
+and	O
+the	O
+role	O
+of	O
+visual	O
+experience	O
+:	O
+dark	O
+rearing	O
+and	O
+monocular	O
+deprivation	O
+.	O
+
+Eleven	O
+patients	O
+tested	O
+positive	O
+for	O
+the	O
+hepatitis	B-GENE
+B	I-GENE
+surface	I-GENE
+antigen	I-GENE
+(	O
+HBsAg	B-GENE
+)	O
+.	O
+
+The	O
+xylose	B-GENE
+isomerase	I-GENE
+-	I-GENE
+encoding	I-GENE
+gene	I-GENE
+(	O
+xylA	B-GENE
+)	O
+of	O
+Clostridium	O
+thermosaccharolyticum	O
+:	O
+cloning	O
+,	O
+sequencing	O
+and	O
+phylogeny	O
+of	O
+XylA	B-GENE
+enzymes	I-GENE
+.	O
+
+Two	O
+phosphopeptides	O
+,	O
+identified	O
+as	O
+RS	O
+-	O
+[	O
+32P	O
+]	O
+SGASGLLTSEHHSR	O
+and	O
+S	O
+-	O
+[	O
+32P	O
+]	O
+SGASGLLTSEHHSR	O
+,	O
+were	O
+obtained	O
+after	O
+stoichiometric	O
+phosphorylation	O
+and	O
+trypsinization	O
+of	O
+the	O
+peptide	O
+.	O
+
+Altogether	O
+,	O
+these	O
+data	O
+suggest	O
+that	O
+Ypt51p	B-GENE
+,	O
+Ypt52p	B-GENE
+,	O
+and	O
+Ypt53p	B-GENE
+are	O
+required	O
+for	O
+transport	O
+in	O
+the	O
+endocytic	O
+pathway	O
+and	O
+for	O
+correct	O
+sorting	O
+of	O
+vacuolar	B-GENE
+hydrolases	I-GENE
+suggesting	O
+a	O
+possible	O
+intersection	O
+of	O
+the	O
+endocytic	O
+with	O
+the	O
+vacuolar	O
+sorting	O
+pathway	O
+.	O
+
+All	O
+of	O
+the	O
+basal	O
+TPN	O
+solutions	O
+were	O
+isonitrogenous	O
+and	O
+identical	O
+in	O
+nutrient	O
+composition	O
+,	O
+except	O
+for	O
+the	O
+difference	O
+in	O
+energy	O
+level	O
+,	O
+which	O
+was	O
+adjusted	O
+with	O
+glucose	O
+.	O
+
+Surprisingly	O
+,	O
+TFIIIC	B-GENE
+alpha	I-GENE
+has	O
+no	O
+homology	O
+to	O
+any	O
+of	O
+the	O
+yeast	B-GENE
+TFIIIC	I-GENE
+subunits	I-GENE
+already	O
+cloned	O
+,	O
+suggesting	O
+a	O
+significant	O
+degree	O
+of	O
+evolutionary	O
+divergence	O
+for	O
+RNA	B-GENE
+polymerase	I-GENE
+III	I-GENE
+factors	I-GENE
+.	O
+
+Transactivation	O
+domain	O
+is	O
+located	O
+downstream	O
+of	O
+the	O
+128	B-GENE
+-	I-GENE
+amino	I-GENE
+-	I-GENE
+acid	I-GENE
+runt	I-GENE
+homology	I-GENE
+region	I-GENE
+,	O
+referred	O
+to	O
+as	O
+the	O
+Runt	B-GENE
+domain	I-GENE
+.	O
+
+We	O
+estimate	O
+that	O
+the	O
+protease	O
+activity	O
+is	O
+at	O
+least	O
+35	O
+-	O
+fold	O
+greater	O
+in	O
+mature	O
+B	O
+cells	O
+than	O
+in	O
+pre	O
+-	O
+B	O
+cells	O
+.	O
+
+The	O
+ligand	O
+for	O
+RXR	B-GENE
+,	O
+9	O
+-	O
+cis	O
+retinoic	O
+acid	O
+,	O
+has	O
+the	O
+opposite	O
+effect	O
+of	O
+destabilizing	O
+the	O
+heterodimeric	O
+-	O
+DNA	O
+complex	O
+.	O
+
+Cerebral125	B-GENE
+albumin	I-GENE
+was	O
+increased	O
+to	O
+similar	O
+proportions	O
+in	O
+those	O
+groups	O
+submitted	O
+to	O
+hyperosmolality	O
+.	O
+
+Retrogradely	O
+labelled	O
+neurons	O
+significantly	O
+prevailed	O
+in	O
+the	O
+ipsilateral	O
+substantia	O
+nigra	O
+pars	O
+compacta	O
+.	O
+
+Therefore	O
+,	O
+the	O
+amino	O
+-	O
+terminal	O
+sequence	O
+of	O
+the	O
+purified	O
+carA	B-GENE
+product	I-GENE
+is	O
+identical	O
+to	O
+that	O
+derived	O
+from	O
+the	O
+nucleotide	O
+sequence	O
+in	O
+both	O
+organisms	O
+,	O
+P	O
+.	O
+stutzeri	O
+having	O
+four	O
+additional	O
+amino	O
+acids	O
+.	O
+
+Aneurysmal	O
+bone	O
+cyst	O
+of	O
+the	O
+jaws	O
+:	O
+analysis	O
+of	O
+11	O
+cases	O
+.	O
+
+Location	O
+and	O
+orientation	O
+of	O
+an	O
+activating	O
+region	O
+in	O
+the	O
+Escherichia	O
+coli	O
+transcription	O
+factor	O
+,	O
+FNR	B-GENE
+.	O
+
+Moxidectin	O
+(	O
+at	O
+3	O
+times	O
+the	O
+therapeutic	O
+dose	O
+)	O
+did	O
+not	O
+have	O
+deleterious	O
+effects	O
+on	O
+cow	O
+reproductive	O
+performance	O
+as	O
+examined	O
+(	O
+eg	O
+,	O
+at	O
+folliculogenesis	O
+,	O
+ovulation	O
+,	O
+and	O
+the	O
+early	O
+embryonic	O
+phase	O
+of	O
+development	O
+)	O
+.	O
+
+Northern	O
+-	O
+blot	O
+analysis	O
+of	O
+mRNA	O
+from	O
+Avicel	O
+-	O
+grown	O
+N	O
+.	O
+patriciarum	O
+showed	O
+that	O
+xynB	B-GENE
+hybridized	O
+to	O
+a	O
+3	O
+.	O
+4	O
+kb	O
+mRNA	O
+species	O
+.	O
+
+The	O
+variable	O
+regions	O
+of	O
+vertebrate	O
+striated	O
+TnT	B-GENE
+isoforms	I-GENE
+reflect	O
+the	O
+subsequent	O
+addition	O
+and	O
+modification	O
+of	O
+genomic	O
+sequences	O
+to	O
+give	O
+rise	O
+to	O
+members	O
+of	O
+the	O
+TnT	B-GENE
+multigene	I-GENE
+family	I-GENE
+.	O
+
+Simple	O
+reaction	O
+time	O
+(	O
+RT	O
+)	O
+to	O
+a	O
+peripheral	O
+visual	O
+target	O
+(	O
+S2	O
+)	O
+is	O
+shortened	O
+when	O
+a	O
+non	O
+-	O
+informative	O
+cue	O
+(	O
+S1	O
+)	O
+is	O
+flashed	O
+at	O
+the	O
+S2	O
+location	O
+100	O
+-	O
+150	O
+ms	O
+before	O
+target	O
+onset	O
+(	O
+early	O
+facilitation	O
+)	O
+.	O
+
+These	O
+viruses	O
+depend	O
+on	O
+the	O
+host	O
+cell	O
+machinery	O
+for	O
+their	O
+existence	O
+,	O
+and	O
+interference	O
+with	O
+these	O
+processes	O
+typically	O
+interferes	O
+with	O
+other	O
+important	O
+host	O
+physiology	O
+.	O
+
+Treatment	O
+was	O
+well	O
+-	O
+tolerated	O
+.	O
+
+A	O
+concentration	O
+of	O
+12	O
+.	O
+5	O
+ppm	O
+SO2	O
+induced	O
+a	O
+decrease	O
+from	O
+baseline	O
+values	O
+of	O
+approximately	O
+80	O
+%	O
+in	O
+mean	O
+MCA	O
+and	O
+of	O
+roughly	O
+70	O
+%	O
+in	O
+mean	O
+CBF	O
+.	O
+
+We	O
+have	O
+used	O
+these	O
+modified	O
+assay	O
+conditions	O
+to	O
+extend	O
+studies	O
+on	O
+the	O
+transposition	O
+pathway	O
+.	O
+
+Renal	O
+cell	O
+carcinoma	O
+in	O
+children	O
+:	O
+a	O
+single	O
+institution	O
+'	O
+s	O
+experience	O
+.	O
+
+The	O
+data	O
+suggest	O
+that	O
+ICP10	B-GENE
+constitutively	O
+increases	O
+ras	B-GENE
+activity	O
+,	O
+and	O
+its	O
+TM	O
+segment	O
+plays	O
+a	O
+critical	O
+role	O
+in	O
+transformation	O
+-	O
+related	O
+signaling	O
+pathways	O
+.	O
+
+Five	O
+concensus	O
+poly	O
+A	O
+addition	O
+sites	O
+are	O
+located	O
+in	O
+the	O
+350	O
+base	O
+pairs	O
+immediately	O
+following	O
+the	O
+protein	B-GENE
+IX	I-GENE
+coding	O
+region	O
+.	O
+
+Factors	O
+associated	O
+with	O
+intrafamilial	O
+transmission	O
+of	O
+hepatitis	O
+B	O
+virus	O
+infection	O
+in	O
+Korea	O
+.	O
+
+Northern	O
+analysis	O
+,	O
+to	O
+search	O
+for	O
+a	O
+pcbAB	B-GENE
+transcript	I-GENE
+,	O
+showed	O
+no	O
+distinct	O
+transcript	O
+and	O
+indicated	O
+severely	O
+degraded	O
+mRNA	O
+.	O
+
+The	O
+high	O
+degree	O
+of	O
+conservation	O
+between	O
+NQO2	B-GENE
+and	O
+NQO1	B-GENE
+gene	I-GENE
+organization	O
+and	O
+sequence	O
+confirmed	O
+that	O
+NQO2	B-GENE
+gene	I-GENE
+encodes	O
+for	O
+a	O
+second	O
+member	O
+of	O
+the	O
+NQO	B-GENE
+gene	I-GENE
+family	I-GENE
+in	O
+human	O
+.	O
+
+The	O
+efficacy	O
+of	O
+a	O
+Propionibacterium	O
+acnes	O
+product	O
+for	O
+treatment	O
+of	O
+coliform	O
+mastitis	O
+was	O
+evaluated	O
+following	O
+intramammary	O
+infusion	O
+of	O
+Escherichia	O
+coli	O
+.	O
+
+The	O
+human	B-GENE
+eps15	I-GENE
+gene	I-GENE
+,	O
+encoding	O
+a	O
+tyrosine	B-GENE
+kinase	I-GENE
+substrate	O
+,	O
+is	O
+conserved	O
+in	O
+evolution	O
+and	O
+maps	O
+to	O
+1p31	O
+-	O
+p32	O
+.	O
+
+The	O
+gene	O
+encoding	O
+the	O
+105	B-GENE
+-	I-GENE
+kDa	I-GENE
+protein	I-GENE
+(	I-GENE
+p105	I-GENE
+)	I-GENE
+precursor	I-GENE
+of	O
+the	O
+p50	B-GENE
+subunit	I-GENE
+of	O
+transcription	O
+factor	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+also	O
+encodes	O
+a	O
+p70	B-GENE
+I	I-GENE
+kappa	I-GENE
+B	I-GENE
+protein	I-GENE
+,	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+gamma	I-GENE
+,	O
+which	O
+is	O
+identical	O
+to	O
+the	O
+C	O
+-	O
+terminal	O
+607	O
+amino	O
+acids	O
+of	O
+p105	B-GENE
+.	O
+
+Alternative	O
+splicing	O
+of	O
+RNA	O
+transcripts	O
+encoded	O
+by	O
+the	O
+murine	O
+p105	B-GENE
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+gene	O
+generates	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+gamma	I-GENE
+isoforms	I-GENE
+with	O
+different	O
+inhibitory	O
+activities	O
+.	O
+
+The	O
+experiment	O
+included	O
+6	O
+male	O
+and	O
+4	O
+female	O
+healthy	O
+subjects	O
+who	O
+,	O
+during	O
+a	O
+24	O
+-	O
+hour	O
+stay	O
+in	O
+the	O
+respiration	O
+chambers	O
+,	O
+performed	O
+,	O
+in	O
+the	O
+morning	O
+and	O
+afternoon	O
+,	O
+15	O
+min	O
+cycling	O
+with	O
+the	O
+total	O
+work	O
+of	O
+6	O
+,	O
+750	O
+kg	O
+m	O
+.	O
+
+These	O
+rearrangements	O
+result	O
+in	O
+the	O
+formation	O
+of	O
+chimeric	O
+genes	O
+showing	O
+the	O
+tyrosine	B-GENE
+kinase	I-GENE
+domain	I-GENE
+of	O
+ret	B-GENE
+fused	O
+with	O
+the	O
+5	O
+'	O
+end	O
+sequences	O
+of	O
+different	O
+genes	O
+.	O
+
+Frequent	O
+loss	O
+of	O
+heterozygosity	O
+(	O
+LOH	O
+)	O
+of	O
+>	O
+30	O
+%	O
+of	O
+the	O
+informative	O
+cases	O
+was	O
+observed	O
+on	O
+chromosomes	O
+3p	O
+(	O
+41	O
+.	O
+1	O
+%	O
+)	O
+,	O
+5q	O
+(	O
+52	O
+.	O
+6	O
+%	O
+)	O
+,	O
+6p	O
+(	O
+30	O
+.	O
+4	O
+%	O
+)	O
+,	O
+8p	O
+(	O
+33	O
+.	O
+3	O
+%	O
+)	O
+,	O
+9p	O
+(	O
+35	O
+.	O
+7	O
+%	O
+)	O
+,	O
+9q	O
+(	O
+30	O
+.	O
+8	O
+%	O
+)	O
+,	O
+11p	O
+(	O
+32	O
+.	O
+4	O
+%	O
+)	O
+,	O
+13q	O
+(	O
+52	O
+.	O
+7	O
+%	O
+)	O
+,	O
+17p	O
+(	O
+55	O
+.	O
+2	O
+%	O
+)	O
+,	O
+17q	O
+(	O
+33	O
+.	O
+3	O
+%	O
+)	O
+,	O
+18q	O
+(	O
+45	O
+.	O
+7	O
+%	O
+)	O
+,	O
+and	O
+19q	O
+(	O
+30	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+A	O
+single	O
+amino	O
+acid	O
+change	O
+in	O
+the	O
+CPY	B-GENE
+vacuolar	I-GENE
+sorting	I-GENE
+signal	I-GENE
+prevents	O
+this	O
+interaction	O
+.	O
+
+Glutamyl	B-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+and	O
+prolyl	B-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+belong	O
+to	O
+different	O
+classes	O
+of	O
+aminoacyl	B-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetases	I-GENE
+that	O
+are	O
+thought	O
+to	O
+have	O
+evolved	O
+along	O
+independent	O
+evolutionary	O
+pathways	O
+.	O
+
+Using	O
+the	O
+sequence	O
+data	O
+obtained	O
+from	O
+the	O
+human	O
+TCRAC	B-GENE
+/	O
+TCRDC	B-GENE
+region	O
+,	O
+we	O
+have	O
+extended	O
+a	O
+polymerase	O
+chain	O
+reaction	O
+-	O
+based	O
+assay	O
+to	O
+test	O
+for	O
+the	O
+expression	O
+of	O
+the	O
+individual	O
+TCRAJ	B-GENE
+gene	I-GENE
+segments	I-GENE
+.	O
+
+This	O
+analysis	O
+revealed	O
+an	O
+intact	O
+gene	O
+(	O
+arg4	B-GENE
+)	O
+showing	O
+a	O
+high	O
+degree	O
+of	O
+homology	O
+with	O
+the	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+CPA2	I-GENE
+gene	I-GENE
+encoding	O
+the	O
+large	O
+subunit	O
+of	O
+carbamoyl	B-GENE
+-	I-GENE
+phosphate	I-GENE
+synthetase	I-GENE
+(	O
+CPS	B-GENE
+-	I-GENE
+A	I-GENE
+)	O
+.	O
+
+The	O
+baroreflex	O
+latency	O
+(	O
+from	O
+the	O
+ECG	O
+R	O
+-	O
+wave	O
+to	O
+the	O
+integrated	O
+MSNA	O
+burst	O
+peak	O
+)	O
+was	O
+constant	O
+at	O
+approximately	O
+1	O
+.	O
+20	O
+s	O
+during	O
+sleep	O
+,	O
+suggesting	O
+that	O
+pulse	O
+-	O
+synchronicity	O
+was	O
+maintained	O
+.	O
+
+DESIGN	O
+-	O
+-	O
+A	O
+randomised	O
+study	O
+was	O
+conducted	O
+in	O
+all	O
+women	O
+aged	O
+50	O
+-	O
+70	O
+years	O
+who	O
+were	O
+eligible	O
+for	O
+breast	O
+cancer	O
+screening	O
+and	O
+living	O
+in	O
+the	O
+city	O
+of	O
+Utrecht	O
+.	O
+
+Identification	O
+of	O
+an	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+gene	I-GENE
+in	O
+the	O
+Marek	O
+'	O
+s	O
+disease	O
+virus	O
+long	O
+internal	O
+repeat	O
+region	O
+which	O
+encodes	O
+a	O
+unique	O
+14	O
+-	O
+kilodalton	O
+polypeptide	O
+.	O
+
+We	O
+have	O
+used	O
+a	O
+full	O
+-	O
+length	O
+cDNA	O
+clone	O
+of	O
+a	O
+mouse	O
+hepatitis	O
+virus	O
+strain	O
+A59	O
+defective	O
+interfering	O
+(	O
+DI	O
+)	O
+RNA	O
+,	O
+pMIDI	B-GENE
+-	I-GENE
+C	I-GENE
+,	O
+and	O
+cassette	O
+mutagenesis	O
+to	O
+study	O
+the	O
+mechanism	O
+of	O
+coronavirus	O
+subgenomic	O
+mRNA	O
+synthesis	O
+.	O
+
+To	O
+study	O
+the	O
+structure	O
+-	O
+function	O
+of	O
+the	O
+gene	B-GENE
+5	I-GENE
+product	I-GENE
+,	O
+wild	O
+-	O
+type	O
+and	O
+mutant	O
+forms	O
+of	O
+NS53	B-GENE
+were	O
+produced	O
+by	O
+using	O
+a	O
+recombinant	O
+baculovirus	O
+expression	O
+system	O
+and	O
+a	O
+recombinant	O
+vaccinia	O
+virus	O
+/	O
+T7	O
+(	O
+vTF7	O
+-	O
+3	O
+)	O
+expression	O
+system	O
+.	O
+
+Gel	O
+electrophoresis	O
+and	O
+Western	O
+immunoblot	O
+analyses	O
+of	O
+intracellular	O
+fractions	O
+derived	O
+from	O
+infected	O
+cells	O
+revealed	O
+that	O
+large	O
+amounts	O
+of	O
+NS53	B-GENE
+were	O
+present	O
+in	O
+the	O
+cytosol	O
+and	O
+in	O
+association	O
+with	O
+the	O
+cytoskeletal	O
+matrix	O
+.	O
+
+The	O
+transcription	B-GENE
+factor	I-GENE
+AP	I-GENE
+-	I-GENE
+2	I-GENE
+is	O
+encoded	O
+by	O
+a	O
+gene	O
+located	O
+on	O
+chromosome	O
+6	O
+near	O
+the	O
+HLA	B-GENE
+locus	I-GENE
+.	O
+
+The	O
+mature	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+mRNA	I-GENE
+is	O
+spliced	O
+from	O
+7	O
+exons	O
+distributed	O
+over	O
+a	O
+region	O
+of	O
+18	O
+kb	O
+genomic	O
+DNA	O
+.	O
+
+San	O
+Martin	O
+'	O
+s	O
+psychological	O
+traits	O
+coupled	O
+to	O
+his	O
+work	O
+with	O
+masonic	O
+lodges	O
+that	O
+allowed	O
+him	O
+to	O
+display	O
+his	O
+abilities	O
+as	O
+strategist	O
+and	O
+political	O
+ruler	O
+.	O
+
+The	O
+participants	O
+were	O
+homosexual	O
+men	O
+in	O
+hepatitis	O
+B	O
+vaccine	O
+trials	O
+in	O
+Amsterdam	O
+(	O
+n	O
+=	O
+74	O
+)	O
+,	O
+New	O
+York	O
+City	O
+(	O
+n	O
+=	O
+120	O
+)	O
+,	O
+and	O
+San	O
+Francisco	O
+(	O
+n	O
+=	O
+168	O
+)	O
+.	O
+
+Comparison	O
+with	O
+the	O
+crystal	O
+structure	O
+of	O
+Desulfovibrio	O
+gigas	O
+,	O
+Dg	O
+,	O
+Fd	B-GENE
+(	O
+Kissinger	O
+et	O
+al	O
+.	O
+,	O
+1991	O
+)	O
+reveals	O
+a	O
+very	O
+similar	O
+folding	O
+topology	O
+,	O
+although	O
+several	O
+secondary	O
+structural	O
+elements	O
+are	O
+extended	O
+in	O
+Pf	O
+relative	O
+to	O
+Dg	O
+Fd	B-GENE
+.	O
+
+CONCLUSIONS	O
+:	O
+Serum	B-GENE
+prolactin	I-GENE
+concentrations	O
+show	O
+age	O
+related	O
+variations	O
+in	O
+presumably	O
+fertile	O
+men	O
+.	O
+
+Eight	O
+highly	O
+trained	O
+male	O
+kayakers	O
+were	O
+studied	O
+to	O
+determine	O
+the	O
+relationship	O
+between	O
+critical	O
+power	O
+(	O
+CP	O
+)	O
+and	O
+the	O
+onset	O
+of	O
+blood	O
+lactate	O
+accumulation	O
+(	O
+OBLA	O
+)	O
+.	O
+
+As	O
+in	O
+S	O
+.	O
+cerevisiae	O
+,	O
+the	O
+sequence	O
+of	O
+rhp51	B-GENE
++	I-GENE
+showed	O
+two	O
+MluI	B-GENE
+cell	I-GENE
+-	I-GENE
+cycle	I-GENE
+boxes	I-GENE
+and	O
+a	O
+putative	O
+DNA	O
+damage	O
+-	O
+responsive	O
+element	O
+in	O
+its	O
+upstream	O
+region	O
+.	O
+
+A	O
+partial	O
+cDNA	O
+sequence	O
+indicated	O
+that	O
+the	O
+T	B-GENE
+lymphocyte	I-GENE
+early	I-GENE
+-	I-GENE
+activation	I-GENE
+gene	I-GENE
+(	O
+Tea	B-GENE
+)	O
+encodes	O
+a	O
+protein	O
+related	O
+to	O
+the	O
+dual	O
+-	O
+function	O
+ecotropic	B-GENE
+retrovirus	I-GENE
+receptor	I-GENE
+/	O
+cationic	B-GENE
+amino	I-GENE
+acid	I-GENE
+transporter	I-GENE
+(	O
+ecoR	B-GENE
+/	O
+CAT1	B-GENE
+)	O
+,	O
+and	O
+RNA	O
+blots	O
+suggested	O
+highest	O
+Tea	B-GENE
+expression	O
+in	O
+T	O
+lymphocytes	O
+and	O
+liver	O
+(	O
+MacLeod	O
+,	O
+C	O
+.	O
+L	O
+.	O
+,	O
+Finley	O
+,	O
+K	O
+.	O
+,	O
+Kakuda	O
+,	O
+D	O
+.	O
+
+Furthermore	O
+,	O
+unlike	O
+the	O
+case	O
+for	O
+HIS3	B-GENE
+where	O
+only	O
+a	O
+limited	O
+subset	O
+of	O
+TATA	O
+-	O
+like	O
+sequences	O
+can	O
+activate	O
+transcription	O
+in	O
+conjunction	O
+with	O
+GCN4p	B-GENE
+,	O
+many	O
+divergent	O
+TATA	O
+-	O
+like	O
+sequences	O
+allowed	O
+GCN4p	B-GENE
+activation	O
+of	O
+TRP3	B-GENE
+.	O
+
+Bacterially	O
+expressed	O
+protein	O
+,	O
+as	O
+well	O
+as	O
+the	O
+in	O
+vitro	O
+reticulocyte	O
+lysate	O
+translation	O
+product	O
+,	O
+comigrated	O
+with	O
+the	O
+purified	O
+37	O
+-	O
+kDa	O
+protein	O
+on	O
+sodium	O
+dodecyl	O
+sulfate	O
+-	O
+polyacrylamide	O
+gels	O
+.	O
+
+In	O
+addition	O
+,	O
+this	O
+kinase	O
+is	O
+well	O
+conserved	O
+evolutionarily	O
+,	O
+ubiquitously	O
+expressed	O
+,	O
+and	O
+its	O
+genes	O
+map	O
+to	O
+a	O
+position	O
+on	O
+human	O
+chromosome	O
+1	O
+frequently	O
+deleted	O
+in	O
+the	O
+late	O
+stages	O
+of	O
+tumorigenesis	O
+.	O
+
+Deletion	O
+analysis	O
+of	O
+the	O
+ICL1	B-GENE
+promoter	I-GENE
+led	O
+to	O
+the	O
+identification	O
+of	O
+an	O
+upstream	O
+activating	O
+sequence	O
+element	O
+,	O
+UASICL1	O
+(	O
+5	O
+'	O
+CATTCATCCG	O
+3	O
+'	O
+)	O
+,	O
+necessary	O
+and	O
+sufficient	O
+for	O
+conferring	O
+carbon	O
+source	O
+-	O
+dependent	O
+regulation	O
+on	O
+a	O
+heterologous	O
+reporter	O
+gene	O
+.	O
+
+In	O
+Mv1Lu	O
+lung	O
+epithelial	O
+cells	O
+,	O
+ActR	B-GENE
+-	I-GENE
+IB	I-GENE
+and	O
+T	B-GENE
+beta	I-GENE
+R	I-GENE
+-	I-GENE
+I	I-GENE
+signal	O
+a	O
+common	O
+set	O
+of	O
+growth	O
+-	O
+inhibitory	O
+and	O
+transcriptional	O
+responses	O
+in	O
+association	O
+with	O
+their	O
+corresponding	O
+ligands	O
+and	O
+type	B-GENE
+II	I-GENE
+receptors	I-GENE
+.	O
+
+H	O
+-	O
+7	O
+,	O
+which	O
+specifically	O
+,	O
+although	O
+weakly	O
+,	O
+inhibited	O
+PKC	B-GENE
+activation	O
+,	O
+had	O
+no	O
+effect	O
+on	O
+tyrosine	O
+phosphorylation	O
+and	O
+PtdIns	O
+(	O
+3	O
+,	O
+4	O
+)	O
+P2	O
+production	O
+.	O
+
+The	O
+effects	O
+of	O
+systemic	O
+glucose	O
+concentration	O
+on	O
+brain	O
+metabolism	O
+following	O
+repeated	O
+brain	O
+ischemia	O
+.	O
+
+A	O
+-	O
+69	O
+-	O
+year	O
+-	O
+old	O
+patient	O
+with	O
+postoperative	O
+small	O
+-	O
+bowel	O
+obstruction	O
+underwent	O
+laparotomy	O
+three	O
+times	O
+.	O
+
+On	O
+physical	O
+examination	O
+a	O
+mild	O
+symmetrical	O
+polyarthritis	O
+of	O
+small	O
+and	O
+large	O
+joints	O
+was	O
+seen	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+SIMV	O
+is	O
+useful	O
+in	O
+weaning	O
+neonates	O
+from	O
+the	O
+ventilator	O
+.	O
+
+VP	O
+-	O
+16	O
+,	O
+ifosfamide	O
+and	O
+cisplatin	O
+(	O
+VIP	O
+)	O
+for	O
+extensive	O
+small	O
+cell	O
+lung	O
+cancer	O
+.	O
+
+A	O
+total	O
+of	O
+7	O
+(	O
+4	O
+males	O
+and	O
+3	O
+females	O
+)	O
+patients	O
+were	O
+included	O
+in	O
+this	O
+retrospective	O
+study	O
+to	O
+determine	O
+the	O
+sensitivity	O
+of	O
+radioimmunoscintigraphy	O
+with	O
+I	O
+-	O
+131	O
+labeled	O
+anti	B-GENE
+CEA	I-GENE
+/	O
+CA	B-GENE
+19	I-GENE
+-	I-GENE
+9	I-GENE
+monoclonal	O
+antibodies	O
+.	O
+
+A	O
+genomic	O
+clone	O
+for	O
+the	O
+cyc07	B-GENE
+gene	I-GENE
+,	O
+which	O
+is	O
+expressed	O
+specifically	O
+at	O
+the	O
+S	O
+phase	O
+during	O
+the	O
+cell	O
+cycle	O
+in	O
+synchronous	O
+cultures	O
+of	O
+periwinkle	O
+(	O
+Catharanthus	O
+roseus	O
+)	O
+cells	O
+,	O
+was	O
+isolated	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Translocation	O
+of	O
+bacteria	O
+or	O
+endotoxin	O
+from	O
+the	O
+gastrointestinal	O
+tract	O
+into	O
+the	O
+bloodstream	O
+has	O
+been	O
+noted	O
+in	O
+animal	O
+experiments	O
+;	O
+however	O
+,	O
+translocation	O
+was	O
+not	O
+detected	O
+in	O
+our	O
+patients	O
+with	O
+hemorrhagic	O
+shock	O
+.	O
+
+Southern	O
+blotting	O
+analysis	O
+implied	O
+the	O
+occurrence	O
+of	O
+multiple	O
+COXVb	B-GENE
+genes	I-GENE
+in	O
+the	O
+rat	O
+genome	O
+.	O
+
+Acylation	O
+with	O
+the	O
+palmitate	O
+analog	O
+was	O
+prevented	O
+when	O
+Gly	O
+-	O
+2	O
+was	O
+mutated	O
+to	O
+alanine	O
+,	O
+implying	O
+that	O
+N	O
+-	O
+myristylation	O
+is	O
+required	O
+for	O
+palmitylation	O
+,	O
+and	O
+when	O
+either	O
+Cys	O
+-	O
+3	O
+or	O
+Cys	O
+-	O
+6	O
+was	O
+mutated	O
+to	O
+serine	O
+.	O
+
+Subunit	O
+composition	O
+and	O
+domain	O
+structure	O
+of	O
+the	O
+Spo0A	B-GENE
+sporulation	I-GENE
+transcription	I-GENE
+factor	I-GENE
+of	I-GENE
+Bacillus	I-GENE
+subtilis	I-GENE
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+analysis	O
+indicates	O
+that	O
+NF	B-GENE
+-	I-GENE
+IL	I-GENE
+-	I-GENE
+6	I-GENE
+,	O
+as	O
+well	O
+as	O
+other	O
+related	O
+members	O
+of	O
+this	O
+family	O
+,	O
+bind	O
+specifically	O
+to	O
+the	O
+NF	B-GENE
+-	I-GENE
+IL	I-GENE
+-	I-GENE
+6	I-GENE
+site	O
+in	O
+the	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+promoter	I-GENE
+.	O
+
+BYV	O
+,	O
+citrus	O
+tristeza	O
+virus	O
+(	O
+CTV	O
+)	O
+,	O
+beet	O
+yellow	O
+stunt	O
+virus	O
+(	O
+BYSV	O
+)	O
+and	O
+carnation	O
+necrotic	O
+fleck	O
+virus	O
+templates	O
+produced	O
+1	O
+kb	O
+amplification	O
+products	O
+,	O
+which	O
+were	O
+shown	O
+by	O
+sequencing	O
+to	O
+represent	O
+fragments	O
+of	O
+the	O
+respective	O
+HSP70	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+p53	B-GENE
+tumor	I-GENE
+suppressor	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+a	O
+sequence	O
+-	O
+specific	O
+DNA	O
+-	O
+binding	O
+protein	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+act	O
+as	O
+a	O
+transcriptional	O
+activator	O
+and	O
+repressor	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+chromosomal	O
+segment	O
+64AB	O
+,	O
+a	O
+region	O
+containing	O
+the	O
+glutamic	B-GENE
+acid	I-GENE
+decarboxylase	I-GENE
+gene	I-GENE
+.	O
+
+Rearrangements	O
+of	O
+the	O
+NFKB2	B-GENE
+gene	I-GENE
+are	O
+associated	O
+with	O
+lymphoid	O
+malignancies	O
+,	O
+but	O
+the	O
+functional	O
+significance	O
+of	O
+these	O
+alterations	O
+is	O
+not	O
+known	O
+.	O
+
+Cloning	O
+and	O
+sequencing	O
+of	O
+the	O
+corresponding	O
+cDNAs	O
+indicates	O
+that	O
+,	O
+via	O
+alternative	O
+splicing	O
+,	O
+the	O
+rearranged	O
+gene	O
+codes	O
+for	O
+two	O
+proteins	O
+of	O
+84	O
+and	O
+85	O
+kD	O
+(	O
+p84	B-GENE
+/	I-GENE
+85	I-GENE
+)	O
+which	O
+retain	O
+the	O
+DNA	O
+-	O
+binding	O
+rel	B-GENE
+domain	I-GENE
+and	O
+the	O
+first	O
+five	O
+ankyrin	B-GENE
+repeats	O
+,	O
+but	O
+have	O
+lost	O
+their	O
+carboxy	O
+-	O
+terminus	O
+including	O
+the	O
+seventh	O
+ankyrin	B-GENE
+repeat	O
+.	O
+
+Transient	O
+co	O
+-	O
+transfection	O
+assays	O
+involving	O
+NFKB2	B-GENE
+expression	O
+vectors	O
+and	O
+kappa	B-GENE
+B	I-GENE
+-	O
+driven	O
+reporter	O
+plasmids	O
+indicate	O
+that	O
+NFKB2	B-GENE
+p85	B-GENE
+has	O
+lost	O
+the	O
+transcriptional	O
+repressor	O
+functions	O
+typical	O
+of	O
+normal	O
+NFKB2	B-GENE
+p52	B-GENE
+.	O
+
+Also	O
+,	O
+HR21ap	B-GENE
+as	O
+well	O
+as	O
+HR21Xap	B-GENE
+are	O
+specific	O
+in	O
+their	O
+inhibition	O
+of	O
+Sp1	B-GENE
+binding	O
+.	O
+
+Intravenous	O
+antibiotic	O
+therapy	O
+in	O
+cystic	O
+fibrosis	O
+:	O
+in	O
+hospital	O
+or	O
+at	O
+home	O
+?	O
+
+Open	O
+reading	O
+frames	O
+in	O
+a	O
+4556	O
+nucleotide	O
+sequence	O
+within	O
+MDV	B-GENE
+-	I-GENE
+1	I-GENE
+BamHI	I-GENE
+-	I-GENE
+D	I-GENE
+DNA	I-GENE
+fragment	I-GENE
+:	O
+evidence	O
+for	O
+splicing	O
+of	O
+mRNA	O
+from	O
+a	O
+new	O
+viral	O
+glycoprotein	O
+gene	O
+.	O
+
+The	O
+ns2	B-GENE
+gene	I-GENE
+comprises	O
+an	O
+open	O
+reading	O
+frame	O
+(	O
+ORF	O
+)	O
+encoding	O
+a	O
+putative	O
+nonstructural	O
+(	O
+ns	O
+)	O
+protein	O
+of	O
+279	O
+amino	O
+acids	O
+with	O
+a	O
+predicted	O
+molecular	O
+mass	O
+of	O
+32	O
+-	O
+kDa	O
+.	O
+
+The	O
+hydrophobicity	O
+profile	O
+of	O
+the	O
+methyltransferase	O
+reveals	O
+the	O
+presence	O
+of	O
+at	O
+least	O
+five	O
+potential	O
+transmembrane	O
+domains	O
+.	O
+
+Measurement	O
+of	O
+SaO2	O
+at	O
+moderate	O
+altitude	O
+can	O
+be	O
+helpful	O
+in	O
+the	O
+care	O
+of	O
+both	O
+healthy	O
+and	O
+ill	O
+newborns	O
+or	O
+infants	O
+.	O
+
+To	O
+determine	O
+whether	O
+the	O
+excess	O
+prevalence	O
+of	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+infection	O
+in	O
+US	O
+black	O
+and	O
+Hispanic	O
+homosexual	O
+men	O
+relative	O
+to	O
+white	O
+men	O
+can	O
+be	O
+explained	O
+by	O
+differences	O
+in	O
+sociodemographic	O
+factors	O
+,	O
+history	O
+of	O
+sexually	O
+transmitted	O
+diseases	O
+,	O
+or	O
+sexual	O
+and	O
+drug	O
+-	O
+use	O
+behaviors	O
+,	O
+the	O
+authors	O
+conducted	O
+a	O
+cross	O
+-	O
+sectional	O
+analysis	O
+of	O
+baseline	O
+HIV	O
+-	O
+1	O
+seroprevalence	O
+and	O
+HIV	O
+-	O
+1	O
+risk	O
+factors	O
+among	O
+4	O
+,	O
+475	O
+non	O
+-	O
+Hispanic	O
+white	O
+,	O
+234	O
+Hispanic	O
+white	O
+,	O
+and	O
+194	O
+black	O
+homosexual	O
+men	O
+from	O
+four	O
+centers	O
+in	O
+the	O
+United	O
+States	O
+(	O
+Baltimore	O
+/	O
+Washington	O
+,	O
+DC	O
+,	O
+Pittsburgh	O
+,	O
+Chicago	O
+,	O
+and	O
+Los	O
+Angeles	O
+)	O
+.	O
+
+The	O
+patients	O
+in	O
+one	O
+group	O
+had	O
+intrauterine	O
+catheters	O
+inserted	O
+and	O
+oxytocin	B-GENE
+was	O
+titrated	O
+to	O
+achieve	O
+the	O
+75th	O
+percentile	O
+of	O
+uterine	O
+activity	O
+observed	O
+in	O
+spontaneous	O
+normal	O
+labour	O
+according	O
+to	O
+parity	O
+.	O
+
+Continued	O
+development	O
+of	O
+the	O
+rat	O
+conditioning	O
+paradigm	O
+is	O
+especially	O
+warranted	O
+because	O
+of	O
+the	O
+ability	O
+to	O
+record	O
+sympathetic	O
+nerve	O
+activity	O
+in	O
+intact	O
+,	O
+awake	O
+subjects	O
+and	O
+the	O
+large	O
+number	O
+of	O
+readily	O
+available	O
+genetic	O
+strains	O
+,	O
+which	O
+model	O
+human	O
+pathological	O
+states	O
+.	O
+
+The	O
+ultrastructure	O
+of	O
+retinal	O
+vessels	O
+was	O
+examined	O
+in	O
+three	O
+eyes	O
+from	O
+diabetic	O
+patients	O
+and	O
+two	O
+eyes	O
+from	O
+control	O
+subjects	O
+.	O
+
+The	O
+regulatory	O
+region	O
+also	O
+has	O
+a	O
+sequence	O
+similar	O
+to	O
+the	O
+binding	O
+site	O
+for	O
+a	O
+liver	O
+-	O
+specific	O
+transcription	O
+factor	O
+,	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factor	I-GENE
+1	I-GENE
+(	O
+HNF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+at	O
+positions	O
+-	O
+120	O
+to	O
+-	O
+132	O
+.	O
+
+Thus	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+GRE	O
+sufficient	O
+to	O
+account	O
+for	O
+full	O
+glucocorticoid	O
+inducibility	O
+and	O
+an	O
+HNF	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+close	O
+to	O
+the	O
+promoter	O
+that	O
+are	O
+major	O
+determinants	O
+of	O
+transcriptional	O
+control	O
+of	O
+the	O
+Xenopus	B-GENE
+fibrinogen	I-GENE
+B	I-GENE
+beta	I-GENE
+subunit	I-GENE
+gene	I-GENE
+in	O
+cells	O
+from	O
+normal	O
+liver	O
+tissue	O
+.	O
+
+Acad	O
+.	O
+
+The	O
+PRB	B-GENE
+-	I-GENE
+1b	I-GENE
+gene	I-GENE
+encodes	O
+for	O
+a	O
+basic	O
+-	O
+type	O
+component	O
+of	O
+the	O
+pathogenesis	O
+-	O
+related	O
+PR	B-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+family	I-GENE
+.	O
+
+Replacement	O
+of	O
+the	O
+CRE	O
+with	O
+a	O
+second	O
+copy	O
+of	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+results	O
+in	O
+a	O
+level	O
+of	O
+transcriptional	O
+activity	O
+comparable	O
+with	O
+that	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+sequence	O
+,	O
+but	O
+replacement	O
+of	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+with	O
+a	O
+CRE	O
+abolishes	O
+activity	O
+.	O
+
+The	O
+T	B-GENE
+-	I-GENE
+cyt	I-GENE
+promoter	I-GENE
+,	O
+although	O
+of	O
+bacterial	O
+origin	O
+is	O
+active	O
+in	O
+planta	O
+and	O
+the	O
+30	B-GENE
+bp	I-GENE
+cyt	I-GENE
+-	I-GENE
+1	I-GENE
+element	I-GENE
+is	O
+located	O
+within	O
+a	O
+region	O
+that	O
+is	O
+essential	O
+for	O
+T	B-GENE
+-	I-GENE
+cyt	I-GENE
+promotor	I-GENE
+activity	O
+in	O
+leaf	O
+,	O
+stem	O
+and	O
+root	O
+cells	O
+of	O
+tobacco	O
+plants	O
+.	O
+
+Reviewing	O
+manuscripts	O
+:	O
+developing	O
+an	O
+efficient	O
+system	O
+.	O
+
+We	O
+suggest	O
+that	O
+CT	O
+scan	O
+be	O
+preferable	O
+in	O
+diagnosis	O
+of	O
+tumors	O
+in	O
+that	O
+area	O
+.	O
+
+Effect	O
+of	O
+aging	O
+on	O
+respiratory	O
+skeletal	O
+muscles	O
+.	O
+
+Two	O
+BASIC	O
+computer	O
+programs	O
+using	O
+logit	O
+transformation	O
+for	O
+the	O
+analysis	O
+of	O
+S	O
+-	O
+shaped	O
+curves	O
+are	O
+presented	O
+.	O
+
+The	O
+yeast	B-GENE
+SSS1	I-GENE
+gene	I-GENE
+is	O
+essential	O
+for	O
+secretory	O
+protein	O
+translocation	O
+and	O
+encodes	O
+a	O
+conserved	O
+protein	O
+of	O
+the	O
+endoplasmic	O
+reticulum	O
+.	O
+
+The	O
+lengths	O
+of	O
+the	O
+complete	O
+polypeptide	O
+chain	O
+of	O
+the	O
+recombinant	O
+enzyme	O
+and	O
+its	O
+transit	O
+peptide	O
+are	O
+388	O
+and	O
+53	O
+residues	O
+,	O
+respectively	O
+.	O
+
+The	O
+absence	O
+of	O
+H4PteGlun	O
+bound	O
+to	O
+the	O
+T	B-GENE
+protein	I-GENE
+in	O
+our	O
+experimental	O
+conditions	O
+demonstrates	O
+that	O
+H4PteGlun	O
+is	O
+not	O
+covalently	O
+linked	O
+to	O
+the	O
+T	B-GENE
+protein	I-GENE
+.	O
+
+TATA	O
+and	O
+CCAAT	O
+boxes	O
+are	O
+located	O
+34	O
+-	O
+bp	O
+and	O
+68	O
+-	O
+bp	O
+,	O
+respectively	O
+,	O
+upstream	O
+of	O
+the	O
+transcription	O
+start	O
+site	O
+,	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+leader	O
+is	O
+78	O
+nucleotides	O
+long	O
+,	O
+and	O
+the	O
+intronless	O
+gene	O
+has	O
+at	O
+least	O
+two	O
+different	O
+polyadenylation	O
+sites	O
+.	O
+
+GGS1	B-GENE
+is	O
+the	O
+same	O
+gene	O
+as	O
+TPS1	B-GENE
+which	O
+was	O
+identified	O
+as	O
+encoding	O
+a	O
+subunit	O
+of	O
+the	O
+trehalose	B-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+phosphate	I-GENE
+synthase	I-GENE
+/	I-GENE
+phosphatase	I-GENE
+complex	I-GENE
+and	O
+it	O
+is	O
+allelic	O
+to	O
+the	O
+fdp1	B-GENE
+,	O
+byp1	B-GENE
+,	O
+glc6	B-GENE
+and	O
+cif1	O
+mutations	O
+.	O
+
+We	O
+also	O
+compared	O
+the	O
+sequence	O
+with	O
+the	O
+partly	O
+homologous	O
+products	O
+of	O
+the	O
+S	O
+.	O
+cerevisiae	O
+genes	O
+TPS2	B-GENE
+and	O
+TSL1	B-GENE
+which	O
+code	O
+for	O
+the	O
+larger	O
+subunits	O
+of	O
+the	O
+trehalose	B-GENE
+synthase	I-GENE
+complex	I-GENE
+and	O
+with	O
+a	O
+TSL1	B-GENE
+homologue	I-GENE
+,	O
+TPS3	B-GENE
+,	O
+of	O
+unknown	O
+function	O
+.	O
+
+Stroop	O
+interference	O
+:	O
+aging	O
+effects	O
+assessed	O
+with	O
+the	O
+Stroop	O
+Color	O
+-	O
+Word	O
+Test	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+study	O
+demonstrates	O
+that	O
+transvaginal	O
+ultrasonography	O
+has	O
+an	O
+efficiency	O
+of	O
+88	O
+%	O
+in	O
+differentiating	O
+endometriomas	O
+from	O
+other	O
+ovarian	O
+masses	O
+with	O
+a	O
+specificity	O
+of	O
+90	O
+%	O
+.	O
+
+Genomic	O
+Southern	O
+blot	O
+analysis	O
+of	O
+rat	B-GENE
+EFIA	I-GENE
+(	O
+gene	O
+encoding	O
+enhancer	B-GENE
+factor	I-GENE
+I	I-GENE
+subunit	I-GENE
+A	I-GENE
+)	O
+reveals	O
+a	O
+complex	O
+band	O
+pattern	O
+when	O
+cDNA	O
+subfragment	O
+probes	O
+are	O
+used	O
+.	O
+
+The	O
+effect	O
+of	O
+ibopamine	O
+and	O
+furosemide	O
+in	O
+130	O
+patients	O
+with	O
+NYHA	O
+Class	O
+I	O
+and	O
+II	O
+heart	O
+failure	O
+were	O
+studied	O
+in	O
+a	O
+parallel	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+randomized	O
+placebo	O
+-	O
+controlled	O
+multi	O
+-	O
+centre	O
+trial	O
+.	O
+
+The	O
+nit	B-GENE
+-	I-GENE
+3	I-GENE
+gene	I-GENE
+of	I-GENE
+the	I-GENE
+filamentous	I-GENE
+fungus	I-GENE
+Neurospora	I-GENE
+crassa	I-GENE
+encodes	O
+nitrate	B-GENE
+reductase	I-GENE
+,	O
+the	O
+enzyme	O
+which	O
+catalyzes	O
+the	O
+first	O
+step	O
+in	O
+nitrate	O
+assimilation	O
+.	O
+
+Unfolding	O
+can	O
+be	O
+described	O
+by	O
+a	O
+two	O
+-	O
+state	O
+process	O
+since	O
+a	O
+ratio	O
+of	O
+delta	O
+Hcalorimetric	O
+to	O
+delta	O
+Hvan	O
+'	O
+t	O
+Hoff	O
+equals	O
+0	O
+.	O
+96	O
+.	O
+
+This	O
+motif	O
+has	O
+been	O
+shown	O
+to	O
+mediate	O
+protein	O
+interactions	O
+in	O
+the	O
+case	O
+of	O
+ankyrin	B-GENE
+as	O
+well	O
+as	O
+several	O
+other	O
+repeat	O
+-	O
+bearing	O
+proteins	O
+.	O
+
+[	B-GENE
+Ala85	I-GENE
+]	I-GENE
+Dk	I-GENE
+(	I-GENE
+69	I-GENE
+-	I-GENE
+85	I-GENE
+)	I-GENE
+retains	O
+full	O
+biological	O
+activity	O
+.	O
+
+The	O
+major	O
+myosin	B-GENE
+-	I-GENE
+binding	I-GENE
+domain	I-GENE
+of	O
+skeletal	B-GENE
+muscle	I-GENE
+MyBP	I-GENE
+-	I-GENE
+C	I-GENE
+(	O
+C	B-GENE
+protein	I-GENE
+)	O
+resides	O
+in	O
+the	O
+COOH	O
+-	O
+terminal	O
+,	O
+immunoglobulin	B-GENE
+C2	B-GENE
+motif	I-GENE
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+periseizure	O
+lipid	O
+accumulation	O
+is	O
+related	O
+to	O
+cortical	O
+oxygenation	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+QLMI	O
+questionnaire	O
+has	O
+good	O
+potential	O
+as	O
+an	O
+instrument	O
+for	O
+assessing	O
+QL	O
+in	O
+post	O
+-	O
+AMI	O
+patients	O
+and	O
+that	O
+it	O
+can	O
+be	O
+successfully	O
+self	O
+-	O
+administered	O
+.	O
+
+Most	O
+smokers	O
+would	O
+prefer	O
+to	O
+quit	O
+smoking	O
+on	O
+their	O
+own	O
+.	O
+
+The	O
+inhibitory	O
+response	O
+to	O
+taps	O
+is	O
+essentially	O
+a	O
+protective	O
+reflex	O
+which	O
+probably	O
+serves	O
+to	O
+reduce	O
+the	O
+activity	O
+of	O
+the	O
+jaw	O
+-	O
+closing	O
+muscles	O
+when	O
+one	O
+bites	O
+unexpectedly	O
+on	O
+hard	O
+objects	O
+.	O
+
+The	O
+action	O
+of	O
+nef	B-GENE
+was	O
+specific	O
+to	O
+the	O
+LTR	O
+,	O
+as	O
+expression	O
+of	O
+nef	B-GENE
+had	O
+no	O
+effect	O
+on	O
+the	O
+activity	O
+of	O
+the	O
+simian	O
+virus	O
+40	O
+,	O
+c	B-GENE
+-	I-GENE
+fms	I-GENE
+,	O
+urokinase	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+,	O
+or	O
+type	B-GENE
+5	I-GENE
+acid	I-GENE
+phosphatase	I-GENE
+promoter	I-GENE
+.	O
+trans	O
+-	O
+activating	O
+activity	O
+was	O
+also	O
+manifested	O
+by	O
+a	O
+frameshift	O
+mutant	O
+expressing	O
+only	O
+the	O
+first	O
+35	O
+amino	O
+acids	O
+of	O
+the	O
+protein	O
+.	O
+
+The	O
+product	O
+of	O
+the	O
+vpr	B-GENE
+open	I-GENE
+reading	I-GENE
+frame	I-GENE
+of	I-GENE
+human	I-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+is	O
+a	O
+15	O
+-	O
+kDa	O
+,	O
+arginine	O
+-	O
+rich	O
+protein	O
+that	O
+is	O
+present	O
+in	O
+virions	O
+in	O
+molar	O
+quantities	O
+equivalent	O
+to	O
+that	O
+of	O
+Gag	B-GENE
+.	O
+
+The	O
+recombinant	B-GENE
+vaccinia	I-GENE
+virus	I-GENE
+-	I-GENE
+expressed	I-GENE
+mutant	I-GENE
+P1	I-GENE
+polyproteins	I-GENE
+were	O
+analyzed	O
+for	O
+proteolytic	O
+processing	O
+defects	O
+in	O
+cells	O
+coinfected	O
+with	O
+a	O
+recombinant	O
+vaccinia	O
+virus	O
+(	O
+VVP3	O
+)	O
+that	O
+expresses	O
+the	O
+poliovirus	B-GENE
+3CD	I-GENE
+protease	I-GENE
+and	O
+for	O
+processing	O
+and	O
+assembly	O
+defects	O
+by	O
+using	O
+a	O
+trans	O
+complementation	O
+system	O
+in	O
+which	O
+P1	B-GENE
+-	O
+expressing	O
+recombinant	O
+vaccinia	O
+viruses	O
+provide	O
+capsid	B-GENE
+precursor	I-GENE
+to	O
+a	O
+defective	O
+poliovirus	O
+genome	O
+that	O
+does	O
+not	O
+express	O
+functional	O
+capsid	B-GENE
+proteins	I-GENE
+(	O
+D	O
+.	O
+
+In	O
+contrast	O
+,	O
+capsid	B-GENE
+proteins	I-GENE
+derived	O
+from	O
+the	O
+P1	B-GENE
+precursor	I-GENE
+with	O
+a	O
+valine	O
+substitution	O
+at	O
+the	O
+amino	O
+terminus	O
+of	O
+VP1	B-GENE
+(	O
+VP1	B-GENE
+-	I-GENE
+G001V	I-GENE
+)	O
+assembled	O
+empty	O
+capsid	O
+particles	O
+but	O
+were	O
+deficient	O
+in	O
+assembling	O
+RNA	O
+-	O
+containing	O
+virions	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+an	O
+18	O
+moth	O
+period	O
+and	O
+out	O
+of	O
+a	O
+total	O
+of	O
+284	O
+positive	O
+blood	O
+cultures	O
+(	O
+154	O
+significant	O
+isolations	O
+)	O
+14	O
+episodes	O
+of	O
+bacteremia	O
+by	O
+M	O
+.	O
+tuberculosis	O
+were	O
+studied	O
+in	O
+12	O
+prison	O
+patients	O
+coinfected	O
+by	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+with	O
+associated	O
+severe	O
+immunosuppression	O
+(	O
+mean	O
+of	O
+CD4	B-GENE
+=	O
+0	O
+.	O
+068	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+l	O
+)	O
+.	O
+
+Acid	O
+instilled	O
+on	O
+the	O
+larynx	O
+of	O
+maturing	O
+rabbits	O
+resulted	O
+in	O
+significant	O
+obstructive	O
+,	O
+central	O
+,	O
+and	O
+mixed	O
+apnea	O
+.	O
+
+By	O
+using	O
+total	O
+-	O
+protein	O
+extracts	O
+from	O
+mycelia	O
+grown	O
+under	O
+penicillin	O
+producing	O
+conditions	O
+we	O
+have	O
+detected	O
+a	O
+DNA	O
+-	O
+binding	O
+activity	O
+that	O
+specifically	O
+shifts	O
+a	O
+promoter	O
+fragment	O
+located	O
+between	O
+-	O
+654	O
+and	O
+-	O
+455	O
+(	O
+relative	O
+to	O
+IPNS	B-GENE
+tsp	I-GENE
+)	O
+.	O
+
+Similar	O
+synergistic	O
+activation	O
+was	O
+observed	O
+in	O
+the	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+promoter	I-GENE
+,	O
+which	O
+also	O
+contains	O
+both	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+and	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+Notice	O
+of	O
+retraction	O
+.	O
+
+No	O
+homology	O
+was	O
+found	O
+between	O
+the	O
+36K	O
+protein	O
+and	O
+known	O
+structures	O
+of	O
+proteins	O
+.	O
+
+We	O
+report	O
+an	O
+odd	O
+case	O
+of	O
+marked	O
+enlargement	O
+of	O
+suprapineal	O
+recess	O
+in	O
+a	O
+patient	O
+with	O
+triventricular	O
+hydrocephalus	O
+.	O
+
+At	O
+a	O
+PaCO2	O
+of	O
+40	O
+mmHg	O
+,	O
+baseline	O
+brain	O
+pHi	O
+measured	O
+7	O
+.	O
+03	O
++	O
+/	O
+-	O
+0	O
+.	O
+04	O
+,	O
+while	O
+regional	O
+cortical	O
+blood	O
+flow	O
+was	O
+47	O
+.	O
+0	O
++	O
+/	O
+-	O
+4	O
+.	O
+3	O
+ml	O
+.	O
+100	O
+g	O
+-	O
+1	O
+.	O
+min	O
+-	O
+1	O
+.	O
+
+CPAP	O
+reduced	O
+isotime	O
+(	O
+defined	O
+as	O
+the	O
+last	O
+common	O
+minute	O
+of	O
+exercise	O
+)	O
+VO2	O
+and	O
+dyspnea	O
+in	O
+those	O
+patients	O
+with	O
+more	O
+severe	O
+lung	O
+disease	O
+,	O
+but	O
+these	O
+values	O
+tended	O
+to	O
+increase	O
+slightly	O
+in	O
+the	O
+patients	O
+with	O
+only	O
+mild	O
+lung	O
+disease	O
+.	O
+
+Effects	O
+of	O
+diltiazem	O
+on	O
+netilmicin	O
+-	O
+induced	O
+nephrotoxicity	O
+in	O
+rabbits	O
+.	O
+
+Four	O
+forms	O
+of	O
+salmonellosis	O
+were	O
+recognised	O
+in	O
+feedlots	O
+and	O
+during	O
+transport	O
+by	O
+sea	O
+:	O
+septicaemic	O
+,	O
+and	O
+acute	O
+,	O
+subacute	O
+and	O
+chronic	O
+enteric	O
+.	O
+
+About	O
+20	O
+%	O
+of	O
+single	O
+-	O
+stranded	O
+DNA	O
+binding	O
+was	O
+observed	O
+in	O
+the	O
+presence	O
+of	O
+MgdTDP	O
+,	O
+but	O
+none	O
+was	O
+detectable	O
+in	O
+the	O
+absence	O
+of	O
+nucleotides	O
+.	O
+
+Both	O
+4	O
+,	O
+8	O
+-	O
+DiMeIQx	O
+and	O
+A	O
+alpha	O
+C	O
+were	O
+found	O
+at	O
+<	O
+1	O
+p	O
+.	O
+p	O
+.	O
+b	O
+.	O
+
+Three	O
+cysteine	O
+and	O
+four	O
+tryptophan	O
+residues	O
+,	O
+previously	O
+identified	O
+as	O
+conserved	O
+amongst	O
+nitrous	B-GENE
+-	I-GENE
+oxide	I-GENE
+reductases	I-GENE
+,	O
+are	O
+found	O
+in	O
+the	O
+Paracoccus	O
+enzyme	O
+.	O
+
+Recombinant	B-GENE
+Leishmania	I-GENE
+surface	I-GENE
+glycoprotein	I-GENE
+GP63	I-GENE
+is	O
+secreted	O
+in	O
+the	O
+baculovirus	O
+expression	O
+system	O
+as	O
+a	O
+latent	O
+metalloproteinase	B-GENE
+.	O
+
+Delineating	O
+the	O
+molecular	O
+basis	O
+for	O
+agonist	O
+-	O
+induced	O
+destabilization	O
+of	O
+mRNA	O
+of	O
+G	B-GENE
+-	I-GENE
+protein	I-GENE
+-	I-GENE
+linked	I-GENE
+receptors	I-GENE
+that	O
+contributes	O
+to	O
+receptor	O
+down	O
+-	O
+regulation	O
+is	O
+fundamental	O
+to	O
+our	O
+understanding	O
+of	O
+long	O
+-	O
+term	O
+regulation	O
+of	O
+receptors	O
+by	O
+agonist	O
+.	O
+
+These	O
+cells	O
+produce	O
+a	O
+low	O
+level	O
+of	O
+IL	B-GENE
+-	I-GENE
+5	I-GENE
+when	O
+stimulated	O
+with	O
+PMA	O
+alone	O
+;	O
+however	O
+,	O
+N6	O
+,	O
+O2	O
+-	O
+dibutyryl	O
+cAMP	O
+(	O
+Bt2cAMP	O
+)	O
+,	O
+in	O
+combination	O
+with	O
+PMA	O
+,	O
+augmented	O
+by	O
+more	O
+than	O
+tenfold	O
+the	O
+IL	B-GENE
+-	I-GENE
+5	I-GENE
+production	O
+at	O
+the	O
+mRNA	O
+and	O
+the	O
+protein	O
+levels	O
+.	O
+
+Hu	B-GENE
+-	I-GENE
+Met	I-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+expression	O
+in	O
+a	O
+small	O
+number	O
+of	O
+human	O
+T	O
+cell	O
+tumor	O
+lines	O
+did	O
+not	O
+correlate	O
+with	O
+any	O
+particular	O
+phenotype	O
+or	O
+stage	O
+of	O
+development	O
+.	O
+
+Partial	O
+engorgement	O
+was	O
+higher	O
+in	O
+the	O
+treatments	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+domain	I-GENE
+,	O
+p56lck	B-GENE
+possesses	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+and	I-GENE
+3	I-GENE
+(	O
+SH2	B-GENE
+and	O
+SH3	B-GENE
+)	O
+domains	O
+as	O
+well	O
+as	O
+a	O
+unique	O
+N	O
+-	O
+terminal	O
+region	O
+.	O
+
+Strains	O
+bearing	O
+the	O
+drs2	B-GENE
+mutation	I-GENE
+process	O
+the	O
+20S	B-GENE
+precursor	I-GENE
+of	O
+the	O
+mature	B-GENE
+18S	I-GENE
+rRNA	I-GENE
+slowly	O
+and	O
+are	O
+deficient	O
+in	O
+40S	B-GENE
+ribosomal	I-GENE
+subunits	I-GENE
+.	O
+
+Hepatitis	O
+B	O
+and	O
+liver	O
+transplantation	O
+.	O
+
+These	O
+combined	O
+observations	O
+define	O
+a	O
+promoter	O
+and	O
+an	O
+enhancer	O
+for	O
+the	O
+chicken	B-GENE
+L	I-GENE
+-	I-GENE
+CAM	I-GENE
+gene	I-GENE
+.	O
+
+Clipping	O
+resulted	O
+in	O
+a	O
+serious	O
+mislocalization	O
+of	O
+the	O
+position	O
+of	O
+the	O
+peak	O
+of	O
+the	O
+epicortical	O
+potential	O
+field	O
+.	O
+
+The	O
+duration	O
+of	O
+diabetes	O
+mellitus	O
+in	O
+these	O
+patients	O
+was	O
+from	O
+5	O
+months	O
+to	O
+6	O
+years	O
+,	O
+and	O
+in	O
+all	O
+patients	O
+this	O
+was	O
+the	O
+first	O
+myocardial	O
+infarction	O
+.	O
+
+The	O
+247	O
+-	O
+kDa	O
+complex	O
+appears	O
+to	O
+contain	O
+two	O
+distinct	O
+protein	O
+-	O
+DNA	O
+complexes	O
+of	O
+approximately	O
+232	O
+and	O
+256	O
+kDa	O
+and	O
+represents	O
+two	O
+proteins	O
+covalently	O
+cross	O
+-	O
+linked	O
+to	O
+a	O
+single	O
+DRE	O
+oligonucleotide	O
+,	O
+while	O
+the	O
+97	O
+,	O
+105	O
+,	O
+and	O
+115	O
+-	O
+kDa	O
+complexes	O
+represent	O
+single	O
+protein	O
+-	O
+DRE	O
+cross	O
+-	O
+links	O
+.	O
+
+The	O
+promoter	O
+and	O
+upstream	O
+region	O
+of	O
+the	O
+Brassica	B-GENE
+napus	I-GENE
+2S	I-GENE
+storage	I-GENE
+protein	I-GENE
+napA	I-GENE
+gene	I-GENE
+were	O
+studied	O
+to	O
+identify	O
+cis	O
+-	O
+acting	O
+sequences	O
+involved	O
+in	O
+developmental	O
+seed	O
+-	O
+specific	O
+expression	O
+.	O
+
+However	O
+,	O
+limited	O
+comparisons	O
+reveal	O
+domains	O
+in	O
+the	O
+NH2	O
+and	O
+COOH	O
+termini	O
+that	O
+have	O
+a	O
+high	O
+degree	O
+of	O
+similarity	O
+suggesting	O
+functional	O
+conservation	O
+.	O
+
+Rinit	O
+reflects	O
+the	O
+Newtonian	O
+resistances	O
+and	O
+Rdiff	O
+represents	O
+the	O
+viscoelastic	O
+/	O
+inhomogeneous	O
+pressure	O
+dissipations	O
+in	O
+the	O
+system	O
+.	O
+
+We	O
+have	O
+explored	O
+the	O
+mechanism	O
+of	O
+action	O
+of	O
+the	O
+fibronectin	B-GENE
+splicing	I-GENE
+enhancer	I-GENE
+and	O
+found	O
+that	O
+the	O
+SE	O
+element	O
+is	O
+required	O
+for	O
+efficient	O
+assembly	O
+of	O
+early	O
+splicing	O
+complexes	O
+,	O
+allowing	O
+a	O
+more	O
+efficient	O
+interaction	O
+of	O
+the	O
+U2	B-GENE
+snRNP	I-GENE
+with	O
+branch	O
+site	O
+sequences	O
+.	O
+
+Inspection	O
+of	O
+enhancer	O
+mutants	O
+suggests	O
+that	O
+trans	O
+-	O
+activation	O
+by	O
+hLEF	B-GENE
+/	O
+GAL4	B-GENE
+is	O
+especially	O
+dependent	O
+on	O
+TCF	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+a	O
+distinct	O
+T	O
+-	O
+cell	O
+-	O
+enriched	O
+protein	O
+that	O
+binds	O
+to	O
+sequences	O
+flanking	O
+the	O
+hLEF	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+in	O
+the	O
+enhancer	O
+.	O
+
+We	O
+conclude	O
+that	O
+sequences	O
+outside	O
+of	O
+the	O
+hLEF	B-GENE
+HMG	I-GENE
+box	I-GENE
+mediate	O
+cell	O
+-	O
+and	O
+context	O
+-	O
+specific	O
+activation	O
+of	O
+the	O
+TCR	B-GENE
+alpha	I-GENE
+enhancer	I-GENE
+and	O
+may	O
+facilitate	O
+interactions	O
+between	O
+hLEF	B-GENE
+and	O
+other	O
+T	O
+-	O
+cell	O
+-	O
+specific	O
+factors	O
+recruited	O
+to	O
+the	O
+enhancer	O
+.	O
+
+A	O
+cAMP	O
+response	O
+element	O
+(	O
+CRE	O
+)	O
+consensus	O
+signal	O
+was	O
+identified	O
+in	O
+the	O
+5	O
+'	O
+-	O
+noncoding	O
+region	O
+.	O
+cAMP	O
+regulates	O
+the	O
+expression	O
+of	O
+Kv1	B-GENE
+.	I-GENE
+5	I-GENE
+gene	I-GENE
+in	O
+a	O
+cell	O
+-	O
+specific	O
+manner	O
+.	O
+
+A	O
+number	O
+of	O
+serological	O
+tests	O
+measuring	O
+the	O
+presence	O
+of	O
+Helicobacter	O
+pylori	O
+-	O
+specific	O
+serum	O
+immunoglobulin	B-GENE
+G	I-GENE
+(	O
+IgG	B-GENE
+)	O
+are	O
+now	O
+commercially	O
+available	O
+.	O
+
+Using	O
+a	O
+series	O
+of	O
+mutant	B-GENE
+T	I-GENE
+antigens	I-GENE
+expressed	O
+by	O
+recombinant	O
+baculoviruses	O
+in	O
+Sf9	O
+cells	O
+,	O
+we	O
+find	O
+that	O
+the	O
+origin	O
+unwinding	O
+activities	O
+of	O
+both	O
+TS677	O
+-	O
+-	O
+>	O
+A	O
+and	O
+TS677	O
+,	O
+679	O
+-	O
+-	O
+>	O
+A	O
+are	O
+inhibited	O
+by	O
+the	O
+T	B-GENE
+-	I-GENE
+antigen	I-GENE
+kinase	I-GENE
+,	O
+as	O
+is	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+T	I-GENE
+antigen	I-GENE
+.	O
+
+The	O
+degree	O
+of	O
+hypoperfusion	O
+was	O
+slightly	O
+related	O
+to	O
+decrease	O
+in	O
+FEV1	O
+.	O
+0	O
+%	O
+,	O
+V25	O
+and	O
+PaO2	O
+and	O
+increase	O
+in	O
+circulating	O
+blood	O
+volume	O
+and	O
+peripheral	O
+red	O
+blood	O
+cell	O
+counts	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+lesions	O
+of	O
+the	O
+OPT	O
+complex	O
+(	O
+the	O
+thalamic	O
+source	O
+of	O
+afferents	O
+to	O
+IHA	O
+and	O
+HD	O
+)	O
+were	O
+found	O
+to	O
+have	O
+no	O
+effect	O
+on	O
+color	O
+-	O
+reversal	O
+learning	O
+performance	O
+.	O
+
+The	O
+fourth	O
+dose	O
+produced	O
+favorable	O
+results	O
+(	O
+66	O
+.	O
+7	O
+%	O
+)	O
+in	O
+individuals	O
+with	O
+HB	B-GENE
+antibodies	I-GENE
+between	O
+10	O
+and	O
+100	O
+IU	O
+/	O
+ml	O
+and	O
+unfavorable	O
+ones	O
+(	O
+3	O
+.	O
+8	O
+%	O
+)	O
+where	O
+the	O
+HB	B-GENE
+antibodies	I-GENE
+were	O
+below	O
+10	O
+IU	O
+/	O
+ml	O
+.	O
+
+CONCLUSIONS	O
+:	O
+In	O
+our	O
+patients	O
+and	O
+within	O
+the	O
+range	O
+of	O
+treatment	O
+variables	O
+studied	O
+,	O
+age	O
+,	O
+Karnofsky	O
+index	O
+,	O
+and	O
+graft	O
+-	O
+versus	O
+-	O
+host	O
+disease	O
+are	O
+the	O
+most	O
+important	O
+factors	O
+related	O
+with	O
+early	O
+mortality	O
+.	O
+
+Nucleotide	O
+sequence	O
+analysis	O
+of	O
+the	O
+HA	B-GENE
+gene	I-GENE
+in	O
+these	O
+two	O
+mutants	O
+confirmed	O
+the	O
+HA	B-GENE
+-	I-GENE
+phenotype	O
+.	O
+
+This	O
+intron	O
+occupies	O
+a	O
+conserved	O
+position	O
+corresponding	O
+to	O
+that	O
+of	O
+intron	O
+1	O
+in	O
+the	O
+transit	O
+peptide	O
+region	O
+of	O
+chloroplast	B-GENE
+GAPDH	I-GENE
+genes	I-GENE
+(	O
+GapA	B-GENE
+and	O
+GapB	B-GENE
+)	O
+of	O
+higher	O
+plants	O
+.	O
+
+The	O
+drug	O
+-	O
+resistant	O
+cell	O
+lines	O
+P388	O
+/	O
+ADR	O
+/	O
+3	O
+and	O
+P388	O
+/	O
+ADR	O
+/	O
+7	O
+express	O
+a	O
+shortened	O
+topo	B-GENE
+II	I-GENE
+alpha	I-GENE
+mRNA	I-GENE
+transcript	I-GENE
+in	O
+addition	O
+to	O
+the	O
+native	O
+transcript	O
+present	O
+in	O
+the	O
+drug	O
+-	O
+sensitive	O
+P388	O
+/	O
+4	O
+cell	O
+line	O
+.	O
+
+Using	O
+a	O
+3	O
+'	O
+-	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+strategy	O
+,	O
+we	O
+have	O
+cloned	O
+cDNAs	O
+representing	O
+the	O
+3	O
+'	O
+-	O
+termini	O
+of	O
+both	O
+the	O
+native	O
+and	O
+mutant	O
+transcripts	O
+from	O
+both	O
+P388	O
+/	O
+ADR	O
+/	O
+3	O
+and	O
+P388	O
+/	O
+ADR	O
+/	O
+7	O
+cells	O
+.	O
+
+The	O
+phi	B-GENE
+AP3	I-GENE
+factor	I-GENE
+is	O
+a	O
+nuclear	O
+phosphoprotein	O
+;	O
+the	O
+extent	O
+of	O
+its	O
+phosphorylation	O
+is	O
+regulated	O
+during	O
+the	O
+cell	O
+cycle	O
+.	O
+
+Similarly	O
+,	O
+the	O
+N	O
+-	O
+terminal	O
+cytoplasmic	O
+domain	O
+of	O
+the	O
+latent	B-GENE
+membrane	I-GENE
+protein	I-GENE
+2A	I-GENE
+(	O
+LMP2A	B-GENE
+)	O
+of	O
+the	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+(	O
+EBV	O
+)	O
+contains	O
+a	O
+single	O
+copy	O
+of	O
+the	O
+Tyr	O
+-	O
+X	O
+-	O
+X	O
+-	O
+Leu	O
+/	O
+Ile	O
+-	O
+containing	O
+motif	O
+which	O
+could	O
+play	O
+a	O
+critical	O
+role	O
+in	O
+B	O
+cell	O
+transformation	O
+.	O
+
+The	O
+functional	O
+homology	O
+of	O
+Cwg2	B-GENE
+with	O
+Cdc43	B-GENE
+,	O
+which	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+control	O
+of	O
+cell	O
+polarity	O
+,	O
+suggests	O
+a	O
+link	O
+between	O
+two	O
+morphogenetic	O
+events	O
+such	O
+as	O
+establishment	O
+of	O
+cell	O
+polarity	O
+and	O
+cell	O
+wall	O
+biosynthesis	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+a	O
+P	B-GENE
+-	I-GENE
+type	I-GENE
+ATPase	I-GENE
+gene	I-GENE
+from	O
+the	O
+cyanobacterium	O
+Synechocystis	O
+sp	O
+.	O
+
+The	O
+cloning	O
+of	O
+PTR2	B-GENE
+represents	O
+the	O
+first	O
+example	O
+of	O
+the	O
+molecular	O
+genetic	O
+characterization	O
+of	O
+a	O
+eucaryotic	O
+peptide	O
+transport	O
+gene	O
+.	O
+
+To	O
+examine	O
+the	O
+biochemical	O
+basis	O
+of	O
+the	O
+end	O
+joining	O
+,	O
+nuclear	O
+extracts	O
+were	O
+prepared	O
+from	O
+a	O
+wide	O
+variety	O
+of	O
+mammalian	O
+cell	O
+lines	O
+and	O
+tested	O
+for	O
+their	O
+ability	O
+to	O
+join	O
+test	O
+plasmid	O
+substrates	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+largest	O
+subunit	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+and	O
+TFIIB	B-GENE
+are	O
+important	O
+determinants	O
+of	O
+transcription	O
+start	O
+site	O
+selection	O
+in	O
+S	O
+.	O
+cerevisiae	O
+and	O
+suggest	O
+that	O
+this	O
+function	O
+might	O
+be	O
+conferred	O
+by	O
+interaction	O
+between	O
+these	O
+two	O
+proteins	O
+.	O
+
+Recombinant	O
+expression	O
+of	O
+a	O
+chimeric	O
+EGFR	B-GENE
+/	O
+ErbB	B-GENE
+-	I-GENE
+3	I-GENE
+receptor	I-GENE
+in	O
+NIH	O
+3T3	O
+fibroblasts	O
+allowed	O
+us	O
+to	O
+investigate	O
+cytoplasmic	O
+events	O
+associated	O
+with	O
+ErbB	B-GENE
+-	I-GENE
+3	I-GENE
+signal	O
+transduction	O
+upon	O
+ligand	O
+activation	O
+.	O
+
+Analysis	O
+of	O
+strains	O
+harboring	O
+an	O
+mds1	B-GENE
+null	I-GENE
+mutation	I-GENE
+demonstrates	O
+that	O
+MDS1	B-GENE
+is	O
+not	O
+essential	O
+during	O
+normal	O
+vegetative	O
+growth	O
+but	O
+appears	O
+to	O
+be	O
+required	O
+for	O
+meiosis	O
+.	O
+
+Val	O
+-	O
+-	O
+>	O
+Ala	O
+mutations	O
+selectively	O
+alter	O
+helix	O
+-	O
+helix	O
+packing	O
+in	O
+the	O
+transmembrane	O
+segment	O
+of	O
+phage	B-GENE
+M13	I-GENE
+coat	I-GENE
+protein	I-GENE
+.	O
+
+Strategic	O
+change	O
+in	O
+the	O
+NHS	O
+.	O
+
+A	O
+much	O
+less	O
+expensive	O
+solution	O
+than	O
+UW	O
+,	O
+containing	O
+only	O
+K	O
+(	O
++	O
+)	O
+-	O
+lactobionate	O
+,	O
+KH2PO4	O
+,	O
+MgSO4	O
+and	O
+raffinose	O
+,	O
+can	O
+be	O
+used	O
+successfully	O
+for	O
+preservation	O
+of	O
+rat	O
+hepatocytes	O
+for	O
+24	O
+hr	O
+for	O
+drug	O
+transport	O
+studies	O
+.	O
+
+Human	B-GENE
+bcl3	I-GENE
+protein	I-GENE
+specifically	O
+displaces	O
+(	B-GENE
+p50	I-GENE
+)	I-GENE
+2	I-GENE
+-	I-GENE
+DNA	I-GENE
+complexes	I-GENE
+.	O
+
+In	O
+vitro	O
+translation	O
+experiments	O
+show	O
+that	O
+human	O
+cDNA	O
+derived	O
+RNA	O
+translates	O
+into	O
+a	O
+protein	O
+with	O
+a	O
+mobility	O
+of	O
+44	O
+-	O
+46	O
+kD	O
+on	O
+SDS	O
+polyacrylamide	O
+gels	O
+.	O
+
+After	O
+peripheral	O
+administration	O
+of	O
+both	O
+CRF	B-GENE
+and	O
+TRH	B-GENE
+,	O
+ACTH	B-GENE
+levels	O
+were	O
+significantly	O
+higher	O
+on	O
+the	O
+tumor	O
+side	O
+in	O
+all	O
+patients	O
+.	O
+
+A	O
+sequence	O
+homology	O
+analysis	O
+between	O
+human	B-GENE
+nm23	I-GENE
+-	I-GENE
+H1	I-GENE
+and	O
+the	O
+homolog	O
+gene	O
+of	O
+the	O
+rat	O
+(	O
+NDP	B-GENE
+-	I-GENE
+K	I-GENE
+beta	I-GENE
+)	O
+shows	O
+that	O
+exon	O
+-	O
+intron	O
+boundaries	O
+are	O
+well	O
+conserved	O
+between	O
+these	O
+two	O
+species	O
+.	O
+
+A	O
+favourable	O
+response	O
+was	O
+achieved	O
+with	O
+a	O
+combination	O
+of	O
+amphotericin	O
+B	O
+and	O
+cotrimoxazole	O
+.	O
+
+Response	O
+durations	O
+were	O
+short	O
+.	O
+
+RESULTS	O
+:	O
+At	O
+the	O
+beginning	O
+of	O
+the	O
+QA	O
+/	O
+QI	O
+process	O
+,	O
+monitoring	O
+of	O
+blood	O
+administration	O
+practices	O
+revealed	O
+that	O
+a	O
+variance	O
+from	O
+institutional	O
+blood	O
+administration	O
+policy	O
+occurred	O
+during	O
+50	O
+percent	O
+of	O
+blood	O
+and	O
+component	O
+transfusions	O
+.	O
+
+Drug	O
+effect	O
+,	O
+measured	O
+as	O
+postural	O
+sway	O
+,	O
+was	O
+also	O
+similar	O
+in	O
+the	O
+patients	O
+with	O
+cirrhosis	O
+and	O
+control	O
+subjects	O
+;	O
+therefore	O
+the	O
+ratio	O
+of	O
+effect	O
+area	O
+under	O
+the	O
+curve	O
+to	O
+concentration	O
+area	O
+under	O
+the	O
+curve	O
+,	O
+a	O
+measure	O
+of	O
+sensitivity	O
+,	O
+did	O
+not	O
+differ	O
+significantly	O
+between	O
+the	O
+patients	O
+with	O
+cirrhosis	O
+and	O
+the	O
+control	O
+subjects	O
+.	O
+
+We	O
+present	O
+evidence	O
+that	O
+YY1	B-GENE
+,	O
+a	O
+ubiquitously	O
+expressed	O
+DNA	O
+-	O
+binding	O
+protein	O
+,	O
+regulates	O
+the	O
+activity	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+promoter	I-GENE
+primarily	O
+through	O
+an	O
+effect	O
+on	O
+DNA	O
+structure	O
+.	O
+
+In	O
+a	O
+retrospective	O
+analysis	O
+of	O
+first	O
+-	O
+time	O
+total	O
+colonoscopies	O
+in	O
+685	O
+patients	O
+,	O
+we	O
+investigated	O
+the	O
+relationship	O
+between	O
+hyperplastic	O
+and	O
+adenomatous	O
+polyps	O
+.	O
+
+The	O
+rate	O
+of	O
+decrement	O
+in	O
+DPOAE	O
+amplitude	O
+over	O
+a	O
+prescribed	O
+time	O
+period	O
+was	O
+utilized	O
+as	O
+a	O
+measure	O
+of	O
+susceptibility	O
+to	O
+the	O
+acoustic	O
+trauma	O
+.	O
+
+Effect	O
+of	O
+single	O
+base	O
+substitutions	O
+at	O
+glycine	O
+-	O
+870	O
+codon	O
+of	O
+gramicidin	B-GENE
+S	I-GENE
+synthetase	I-GENE
+2	I-GENE
+gene	I-GENE
+on	O
+proline	O
+activation	O
+.	O
+
+The	O
+predicted	O
+Pay4p	B-GENE
+sequence	I-GENE
+contains	O
+two	O
+putative	O
+ATP	O
+-	O
+binding	O
+domains	O
+and	O
+shows	O
+structural	O
+relationships	O
+to	O
+other	O
+potential	O
+ATP	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+involved	O
+in	O
+biological	O
+processes	O
+as	O
+diverse	O
+as	O
+peroxisome	O
+biogenesis	O
+,	O
+vesicle	O
+-	O
+mediated	O
+protein	O
+transport	O
+,	O
+cell	O
+cycle	O
+control	O
+,	O
+and	O
+transcriptional	O
+regulation	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+the	O
+structure	O
+of	O
+the	O
+decorin	B-GENE
+gene	I-GENE
+promoter	I-GENE
+is	O
+different	O
+from	O
+that	O
+of	O
+any	O
+other	O
+proteoglycan	O
+promoter	O
+characterized	O
+so	O
+far	O
+and	O
+indicate	O
+that	O
+the	O
+pur	O
+/	O
+pyr	O
+segment	O
+plays	O
+a	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+gene	O
+transcription	O
+.	O
+
+The	O
+kinase	O
+inhibitor	O
+staurosporine	O
+(	O
+1	O
+microM	O
+)	O
+blocks	O
+LPA	O
+-	O
+induced	O
+,	O
+but	O
+not	O
+epidermal	O
+growth	O
+factor	O
+-	O
+induced	O
+,	O
+activation	O
+of	O
+p21ras	B-GENE
+and	O
+MAP	B-GENE
+kinase	I-GENE
+,	O
+consistent	O
+with	O
+an	O
+intermediate	O
+protein	O
+kinase	O
+linking	O
+the	O
+LPA	B-GENE
+receptor	I-GENE
+to	O
+p21ras	B-GENE
+activation	O
+.	O
+
+267	O
+,	O
+4870	O
+-	O
+4877	O
+)	O
+)	O
+indicates	O
+an	O
+overall	O
+identity	O
+of	O
+58	O
+and	O
+56	O
+%	O
+,	O
+respectively	O
+,	O
+with	O
+a	O
+91	O
+and	O
+92	O
+%	O
+identity	O
+in	O
+the	O
+highly	O
+conserved	O
+transmembrane	O
+and	O
+cytoplasmic	O
+domains	O
+.	O
+
+S	O
+.	O
+,	O
+K	O
+.	O
+
+The	O
+survival	O
+rate	O
+at	O
+forty	O
+months	O
+in	O
+15	O
+patients	O
+with	O
+N2	O
+disease	O
+who	O
+underwent	O
+R2b	O
+operation	O
+was	O
+51	O
+%	O
+.	O
+
+Mothers	O
+with	O
+severe	O
+anatomical	O
+abnormalities	O
+,	O
+who	O
+are	O
+HIV	O
+positive	O
+,	O
+have	O
+active	O
+TB	O
+or	O
+whose	O
+children	O
+have	O
+inherited	O
+mono	O
+-	O
+or	O
+disaccharide	O
+intolerances	O
+should	O
+not	O
+breastfeed	O
+.	O
+
+G	O
+.	O
+
+The	O
+psaD	B-GENE
+,	O
+psaF	B-GENE
+,	O
+psaH	B-GENE
+,	O
+and	O
+psaL	B-GENE
+products	I-GENE
+have	O
+two	O
+isoforms	O
+each	O
+that	O
+are	O
+distinguished	O
+by	O
+different	O
+mobilities	O
+in	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+,	O
+and	O
+the	O
+psaE	B-GENE
+product	I-GENE
+has	O
+four	O
+isoforms	O
+.	O
+
+When	O
+Hy	O
+-	O
+Vac	O
+SPF	O
+type	O
+V	O
+embryos	O
+were	O
+exposed	O
+to	O
+either	O
+0	O
+.	O
+20	O
+ml	O
+50	O
+%	O
+ethanol	O
+in	O
+CRS	O
+or	O
+to	O
+0	O
+.	O
+20	O
+ml	O
+CRS	O
+(	O
+controls	O
+)	O
+,	O
+ethanol	O
+-	O
+treated	O
+embryos	O
+showed	O
+a	O
+VSD	O
+incidence	O
+of	O
+34	O
+.	O
+1	O
+%	O
+compared	O
+with	O
+a	O
+3	O
+.	O
+6	O
+%	O
+incidence	O
+in	O
+the	O
+controls	O
+(	O
+P	O
+=	O
+0	O
+.	O
+0017	O
+)	O
+.	O
+
+Peripheral	O
+vitreochorioretinal	O
+dystrophies	O
+in	O
+myopia	O
+patients	O
+
+The	O
+secondary	O
+,	O
+but	O
+not	O
+the	O
+primary	O
+,	O
+antibody	O
+responses	O
+of	O
+male	O
+C57Bl	O
+/	O
+6	O
+mice	O
+were	O
+higher	O
+among	O
+mice	O
+housed	O
+alone	O
+compared	O
+to	O
+mice	O
+housed	O
+in	O
+groups	O
+;	O
+differences	O
+were	O
+observed	O
+for	O
+both	O
+IgM	B-GENE
+and	O
+IgG	B-GENE
+anti	I-GENE
+-	I-GENE
+KLH	I-GENE
+antibodies	I-GENE
+.	O
+
+However	O
+,	O
+a	O
+surprisingly	O
+high	O
+degree	O
+of	O
+conservation	O
+of	O
+intron	O
+sequences	O
+was	O
+observed	O
+between	O
+both	O
+species	O
+.	O
+
+Interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+may	O
+possibly	O
+potentiate	O
+metastasis	O
+of	O
+cardiac	O
+myxoma	O
+.	O
+
+Other	O
+parameters	O
+of	O
+iron	O
+metabolism	O
+,	O
+including	O
+ferritin	B-GENE
+,	O
+were	O
+not	O
+found	O
+to	O
+contribute	O
+to	O
+the	O
+risk	O
+.	O
+
+Responses	O
+to	O
+the	O
+Plowright	O
+Rinderpest	O
+vaccine	O
+by	O
+43	O
+calves	O
+and	O
+70	O
+adult	O
+cattle	O
+in	O
+Uganda	O
+in	O
+1990	O
+,	O
+through	O
+the	O
+production	O
+of	O
+IgG	B-GENE
+antibodies	I-GENE
+,	O
+were	O
+monitored	O
+for	O
+4	O
+weeks	O
+using	O
+the	O
+ELISA	O
+assay	O
+.	O
+
+Tumours	O
+of	O
+the	O
+cavum	O
+oris	O
+and	O
+oropharynx	O
+of	O
+T1	O
+-	O
+stage	O
+are	O
+possible	O
+only	O
+in	O
+1	O
+of	O
+3	O
+cases	O
+.	O
+
+Thomas	O
+'	O
+Hospital	O
+solution	O
+(	O
+with	O
+95	O
+%	O
+O2	O
+:	O
+5	O
+%	O
+CO2	O
+)	O
+can	O
+meet	O
+the	O
+metabolic	O
+demand	O
+of	O
+the	O
+ischaemic	O
+myocardium	O
+and	O
+thus	O
+increase	O
+the	O
+safe	O
+duration	O
+of	O
+cardiac	O
+arrest	O
+.	O
+
+Plasma	O
+,	O
+LDL	B-GENE
+and	O
+liver	O
+cholesterol	O
+concentrations	O
+were	O
+higher	O
+in	O
+the	O
+hyperlipidemic	O
+control	O
+than	O
+the	O
+nonhyperlipidemic	O
+control	O
+and	O
+lower	O
+in	O
+the	O
+groups	O
+fed	O
+diets	O
+containing	O
+pectin	B-GENE
+or	O
+prune	O
+fiber	O
+than	O
+in	O
+the	O
+hyperlipidemic	O
+control	O
+group	O
+.	O
+
+Routine	O
+psychometric	O
+screening	O
+of	O
+IHD	O
+patients	O
+may	O
+provide	O
+a	O
+cost	O
+-	O
+effective	O
+means	O
+of	O
+alerting	O
+cardiologists	O
+and	O
+internists	O
+to	O
+the	O
+relatively	O
+high	O
+levels	O
+of	O
+distress	O
+among	O
+their	O
+patients	O
+.	O
+
+Employing	O
+this	O
+sequence	O
+information	O
+from	O
+c11	O
+/	O
+1	O
+,	O
+the	O
+c11	O
+/	O
+1	O
+-	O
+specific	O
+cDNA	O
+was	O
+generated	O
+from	O
+poly	O
+(	O
+A	O
+)	O
++	O
+RNA	O
+of	O
+bovine	O
+PMNLs	O
+by	O
+reverse	O
+transcription	O
+and	O
+a	O
+combination	O
+of	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+methods	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+mouse	B-GENE
+HO	I-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+is	O
+identical	O
+to	O
+that	O
+of	O
+p32	B-GENE
+,	O
+initially	O
+identified	O
+as	O
+a	O
+stress	O
+-	O
+induced	O
+protein	O
+in	O
+mouse	O
+BALBc	O
+/	O
+3T3	O
+cells	O
+.	O
+
+Using	O
+a	O
+polymerase	O
+chain	O
+reaction	O
+-	O
+based	O
+approach	O
+,	O
+we	O
+cloned	O
+a	O
+150	O
+-	O
+base	O
+pair	O
+fragment	O
+of	O
+a	O
+new	O
+sialymotif	O
+from	O
+human	O
+placenta	O
+mRNA	O
+,	O
+which	O
+was	O
+then	O
+used	O
+as	O
+a	O
+probe	O
+to	O
+clone	O
+the	O
+complete	O
+coding	O
+sequence	O
+of	O
+the	O
+corresponding	O
+gene	O
+from	O
+a	O
+cDNA	O
+library	O
+.	O
+
+The	O
+structural	O
+analysis	O
+also	O
+demonstrated	O
+that	O
+the	O
+heterogeneity	O
+of	O
+the	O
+HDC	B-GENE
+mRNA	I-GENE
+is	O
+caused	O
+by	O
+an	O
+insertion	O
+of	O
+the	O
+seventh	O
+intron	O
+sequence	O
+and	O
+alternative	O
+use	O
+of	O
+the	O
+splicing	O
+acceptor	O
+site	O
+at	O
+the	O
+12th	O
+exon	O
+.	O
+
+A	O
+complementary	O
+DNA	O
+was	O
+isolated	O
+from	O
+Caenorhabditis	O
+elegans	O
+that	O
+encoded	O
+a	O
+polypeptide	O
+of	O
+1438	O
+amino	O
+acid	O
+residues	O
+,	O
+CeGAP	B-GENE
+,	O
+which	O
+contains	O
+a	O
+domain	O
+with	O
+sequence	O
+similarity	O
+to	O
+the	O
+COOH	B-GENE
+-	I-GENE
+terminal	I-GENE
+segment	I-GENE
+(	I-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+region	I-GENE
+)	I-GENE
+of	O
+Bcr	B-GENE
+and	O
+other	O
+known	O
+GTPase	B-GENE
+-	I-GENE
+activating	I-GENE
+proteins	I-GENE
+of	O
+the	O
+Rho	B-GENE
+subfamily	I-GENE
+.	O
+
+Additional	O
+exonuclease	B-GENE
+III	I-GENE
+protection	O
+was	O
+observed	O
+beyond	O
+the	O
+core	O
+region	O
+on	O
+both	O
+the	O
+5	O
+'	O
+and	O
+3	O
+'	O
+sides	O
+,	O
+suggesting	O
+that	O
+E1	B-GENE
+interacted	O
+with	O
+more	O
+distal	O
+sequences	O
+as	O
+well	O
+.	O
+
+Repression	O
+is	O
+alleviated	O
+when	O
+the	O
+two	O
+(	O
+for	O
+E2	B-GENE
+)	O
+or	O
+three	O
+(	O
+for	O
+E2	B-GENE
+-	I-GENE
+C	I-GENE
+)	O
+promoter	O
+-	O
+proximal	O
+copies	O
+of	O
+E2	B-GENE
+-	O
+RS	O
+are	O
+mutated	O
+.	O
+
+A	O
+mutant	O
+in	O
+the	O
+AAV	O
+terminal	O
+resolution	O
+site	O
+(	O
+trs	O
+)	O
+was	O
+defective	O
+for	O
+DNA	O
+replication	O
+in	O
+the	O
+in	O
+vitro	O
+assay	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+rep	B-GENE
+strongly	O
+enhances	O
+the	O
+function	O
+of	O
+negative	O
+regulatory	O
+elements	O
+of	O
+the	O
+LTR	O
+.	O
+
+The	O
+Oct	B-GENE
+-	I-GENE
+3	I-GENE
+/	I-GENE
+4	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+which	O
+belongs	O
+to	O
+the	O
+POU	B-GENE
+family	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+,	O
+is	O
+a	O
+good	O
+candidate	O
+for	O
+regulating	O
+initial	O
+differentiation	O
+decisions	O
+.	O
+
+Using	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+,	O
+we	O
+show	O
+that	O
+the	O
+RAREoct	B-GENE
+contributes	O
+to	O
+the	O
+transcriptional	O
+activation	O
+of	O
+Oct	B-GENE
+-	I-GENE
+3	I-GENE
+/	I-GENE
+4	I-GENE
+promoter	I-GENE
+in	O
+P19	O
+cells	O
+and	O
+,	O
+most	O
+interestingly	O
+,	O
+mediates	O
+the	O
+RA	O
+-	O
+induced	O
+repression	O
+in	O
+RA	O
+-	O
+differentiated	O
+EC	O
+cells	O
+.	O
+
+176	O
+:	O
+787	O
+-	O
+792	O
+,	O
+1992	O
+;	O
+M	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+negative	O
+transcriptional	O
+effect	O
+of	O
+COUP	B-GENE
+-	I-GENE
+TFs	I-GENE
+is	O
+dominant	O
+over	O
+the	O
+activating	O
+effect	O
+of	O
+the	O
+Oct4	B-GENE
+embryonic	I-GENE
+stem	I-GENE
+cell	I-GENE
+-	I-GENE
+specific	I-GENE
+enhancer	I-GENE
+.	O
+
+Analysis	O
+of	O
+mig	B-GENE
+/	O
+CAT	B-GENE
+chimeric	O
+constructs	O
+transiently	O
+transfected	O
+into	O
+the	O
+RAW	O
+264	O
+.	O
+7	O
+mouse	O
+monocytic	O
+cell	O
+line	O
+revealed	O
+a	O
+unique	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+(	O
+gamma	B-GENE
+RE	I-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+When	O
+expressed	O
+alone	O
+in	O
+test	O
+cells	O
+,	O
+Atr	B-GENE
+-	I-GENE
+I	I-GENE
+is	O
+unable	O
+to	O
+bind	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+,	O
+activin	B-GENE
+,	O
+or	O
+bone	B-GENE
+morphogenetic	I-GENE
+protein	I-GENE
+2	I-GENE
+.	O
+
+Therefore	O
+,	O
+Mxi1	B-GENE
+and	O
+Mad	B-GENE
+might	O
+antagonize	O
+Myc	B-GENE
+function	O
+and	O
+are	O
+candidate	O
+tumor	O
+suppressor	O
+genes	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+type	O
+IV	O
+renal	O
+tubular	O
+acidosis	O
+has	O
+not	O
+been	O
+reported	O
+previously	O
+in	O
+association	O
+with	O
+Alport	O
+'	O
+s	O
+syndrome	O
+in	O
+an	O
+adult	O
+patient	O
+.	O
+
+A	O
+cDNA	O
+clone	O
+was	O
+isolated	O
+from	O
+a	O
+chicken	O
+embryo	O
+cDNA	O
+library	O
+employing	O
+a	O
+PCR	O
+-	O
+generated	O
+radiolabeled	O
+probe	O
+specific	O
+for	O
+the	O
+U3	B-GENE
+region	I-GENE
+of	O
+the	O
+Rous	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+LTR	I-GENE
+.	O
+
+Two	O
+basic	O
+patterns	O
+of	O
+locomotor	O
+behavior	O
+and	O
+corresponding	O
+torso	O
+morphology	O
+exist	O
+among	O
+extant	O
+anthropoids	O
+.	O
+
+Animal	O
+age	O
+and	O
+sex	O
+had	O
+no	O
+significant	O
+effects	O
+on	O
+CSF	O
+composition	O
+,	O
+but	O
+serum	O
+IgG	B-GENE
+concentration	O
+increased	O
+with	O
+age	O
+.	O
+
+Fast	O
+continuous	O
+expansion	O
+.	O
+
+A	O
+randomized	O
+,	O
+multicenter	O
+study	O
+comparing	O
+the	O
+efficacy	O
+and	O
+tolerability	O
+of	O
+tropisetron	O
+,	O
+a	O
+new	O
+5	B-GENE
+-	I-GENE
+HT3	I-GENE
+receptor	I-GENE
+antagonist	O
+,	O
+with	O
+a	O
+metoclopramide	O
+-	O
+containing	O
+antiemetic	O
+cocktail	O
+in	O
+the	O
+prevention	O
+of	O
+cisplatin	O
+-	O
+induced	O
+emesis	O
+.	O
+
+Each	O
+repeat	O
+consists	O
+of	O
+12	O
+nt	O
+,	O
+coding	O
+for	O
+the	O
+reiterated	O
+sequence	O
+,	O
+K	O
+/	O
+NPAG	O
+.	O
+
+BACKGROUND	O
+:	O
+To	O
+determine	O
+the	O
+predictors	O
+of	O
+desipramine	O
+-	O
+refractory	O
+depression	O
+,	O
+the	O
+authors	O
+examined	O
+the	O
+outcome	O
+in	O
+patients	O
+with	O
+major	O
+depression	O
+who	O
+were	O
+admitted	O
+to	O
+a	O
+general	O
+hospital	O
+and	O
+treated	O
+with	O
+desipramine	O
+adjusted	O
+to	O
+an	O
+adequate	O
+blood	O
+level	O
+.	O
+
+Analysis	O
+of	O
+the	O
+intact	O
+hGH	B-GENE
+gene	I-GENE
+or	O
+hGH	B-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+flanking	I-GENE
+DNA	I-GENE
+(	I-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+FR	I-GENE
+)	I-GENE
+coupled	O
+to	O
+the	O
+hGh	B-GENE
+cDNA	I-GENE
+or	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+or	O
+luciferase	B-GENE
+genes	I-GENE
+,	O
+indicated	O
+that	O
+cAMP	O
+primarily	O
+stimulated	O
+hGH	B-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+The	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+SAP	B-GENE
+-	I-GENE
+1	I-GENE
+cDNA	I-GENE
+showed	O
+that	O
+mature	B-GENE
+SAP	I-GENE
+-	I-GENE
+1	I-GENE
+consisted	O
+of	O
+1093	O
+amino	O
+acids	O
+and	O
+a	O
+transmembrane	B-GENE
+-	I-GENE
+type	I-GENE
+PTP	I-GENE
+,	O
+which	O
+possessed	O
+a	O
+single	O
+PTP	B-GENE
+-	I-GENE
+conserved	I-GENE
+domain	I-GENE
+in	O
+the	O
+cytoplasmic	O
+region	O
+.	O
+
+Several	O
+features	O
+of	O
+10	O
+.	O
+24	O
+.	O
+6	O
+cells	O
+suggest	O
+that	O
+the	O
+mutation	O
+disrupts	O
+normal	O
+intracellular	O
+formation	O
+of	O
+peptide	B-GENE
+/	I-GENE
+DR	I-GENE
+complexes	I-GENE
+.	O
+
+This	O
+distribution	O
+parallels	O
+that	O
+of	O
+the	O
+neurotransmitters	O
+glutamate	O
+and	O
+aspartate	O
+;	O
+however	O
+,	O
+neither	O
+of	O
+these	O
+excitatory	O
+amino	O
+acids	O
+is	O
+a	O
+substrate	O
+for	O
+transport	O
+.	O
+
+The	O
+Harleco	O
+apparatus	O
+is	O
+a	O
+simple	O
+,	O
+useful	O
+,	O
+cost	O
+-	O
+effective	O
+adjunct	O
+to	O
+the	O
+diagnosis	O
+and	O
+treatment	O
+of	O
+this	O
+life	O
+-	O
+threatening	O
+condition	O
+.	O
+
+Co	O
+-	O
+transfection	O
+of	O
+expression	O
+vectors	O
+for	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	I-GENE
+C	I-GENE
+/	I-GENE
+EBP	I-GENE
+)	I-GENE
+alpha	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+trans	O
+-	O
+activated	O
+the	O
+rat	B-GENE
+uncoupling	I-GENE
+protein	I-GENE
+gene	I-GENE
+promoter	I-GENE
+due	O
+to	O
+sequences	O
+in	O
+the	O
+5	O
+'	O
+proximal	O
+region	O
+.	O
+
+It	O
+was	O
+not	O
+possible	O
+to	O
+study	O
+the	O
+basis	O
+for	O
+tissue	O
+-	O
+specific	O
+expression	O
+of	O
+this	O
+gene	O
+,	O
+because	O
+the	O
+beta	B-GENE
+3	I-GENE
+gene	I-GENE
+promoter	I-GENE
+had	O
+not	O
+been	O
+isolated	O
+previously	O
+.	O
+
+Isolation	O
+and	O
+characterization	O
+of	O
+a	O
+TATA	O
+-	O
+less	O
+promoter	O
+for	O
+the	O
+human	B-GENE
+beta	I-GENE
+3	I-GENE
+integrin	I-GENE
+gene	I-GENE
+.	O
+
+Subretinal	O
+fluid	O
+was	O
+punctured	O
+on	O
+the	O
+poorer	O
+eye	O
+in	O
+19	O
+eyes	O
+(	O
+52	O
+.	O
+7	O
+%	O
+)	O
+and	O
+on	O
+the	O
+better	O
+eye	O
+in	O
+7	O
+eyes	O
+(	O
+19	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+activation	O
+of	O
+these	O
+enzymes	O
+is	O
+not	O
+sufficient	O
+for	O
+the	O
+acute	O
+stimulation	O
+of	O
+glucose	O
+transport	O
+.	O
+
+The	O
+inserted	O
+region	O
+,	O
+which	O
+represents	O
+an	O
+intron	O
+in	O
+brain	O
+and	O
+muscle	O
+,	O
+is	O
+expressed	O
+in	O
+the	O
+tumor	O
+cell	O
+lines	O
+either	O
+as	O
+a	O
+"	O
+readthrough	O
+"	O
+form	O
+or	O
+with	O
+78	O
+residues	O
+deleted	O
+from	O
+its	O
+5	O
+'	O
+end	O
+.	O
+
+Concordance	O
+of	O
+IBDQ	O
+scores	O
+was	O
+tested	O
+in	O
+280	O
+stable	O
+subjects	O
+.	O
+
+Regression	O
+line	O
+slopes	O
+of	O
+IBDQ	O
+scores	O
+were	O
+significantly	O
+different	O
+in	O
+patients	O
+who	O
+deteriorated	O
+from	O
+those	O
+who	O
+remained	O
+stable	O
+(	O
+[	O
+b	O
+]	O
+<	O
+0	O
+.	O
+15	O
+;	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+Inhibition	O
+of	O
+erythromycin	O
+synthesis	O
+by	O
+disruption	O
+of	O
+malonyl	B-GENE
+-	I-GENE
+coenzyme	I-GENE
+A	I-GENE
+decarboxylase	I-GENE
+gene	I-GENE
+eryM	B-GENE
+in	O
+Saccharopolyspora	O
+erythraea	O
+.	O
+
+This	O
+region	O
+is	O
+required	O
+for	O
+activation	O
+of	O
+DNA	O
+binding	O
+of	O
+MyoD	B-GENE
+and	O
+E12	B-GENE
+homodimers	I-GENE
+and	O
+E12	B-GENE
+/	O
+MyoD	B-GENE
+heterodimers	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+of	O
+the	O
+traI	B-GENE
+structural	I-GENE
+gene	I-GENE
+and	O
+application	O
+of	O
+purified	O
+mutant	O
+TraI	B-GENE
+proteins	I-GENE
+for	O
+in	O
+vitro	O
+assays	O
+served	O
+to	O
+evaluate	O
+the	O
+functional	O
+importance	O
+of	O
+conserved	O
+amino	O
+acid	O
+residues	O
+.	O
+
+Concerted	O
+action	O
+of	O
+three	O
+distinct	O
+domains	O
+in	O
+the	O
+DNA	O
+cleaving	O
+-	O
+joining	O
+reaction	O
+catalyzed	O
+by	O
+relaxase	B-GENE
+(	O
+TraI	B-GENE
+)	O
+of	O
+conjugative	O
+plasmid	O
+RP4	O
+.	O
+
+The	O
+COOH	O
+-	O
+terminal	O
+46	O
+codons	O
+of	O
+slyD	B-GENE
+encode	O
+a	O
+remarkable	O
+histidine	O
+-	O
+rich	O
+peptide	O
+sequence	O
+which	O
+is	O
+at	O
+least	O
+partly	O
+dispensable	O
+for	O
+slyD	B-GENE
+function	O
+in	O
+E	B-GENE
+-	O
+mediated	O
+lysis	O
+.	O
+
+We	O
+studied	O
+GSH	O
+-	O
+Px	O
+enzyme	O
+activity	O
+in	O
+serum	O
+after	O
+acute	O
+myocardial	O
+infarction	O
+(	O
+AMI	O
+)	O
+and	O
+unstable	O
+angina	O
+pectoris	O
+(	O
+UAP	O
+)	O
+.	O
+
+The	O
+HGF	B-GENE
+-	O
+induced	O
+cell	O
+motility	O
+was	O
+mimicked	O
+by	O
+12	O
+-	O
+0	O
+-	O
+tetradecanoyl	O
+-	O
+phorbol	O
+-	O
+13	O
+-	O
+acetate	O
+,	O
+a	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+-	O
+activating	O
+phorbol	O
+ester	O
+,	O
+but	O
+not	O
+by	O
+Ca2	O
++	O
+ionophore	O
+.	O
+
+In	O
+addition	O
+,	O
+lexical	O
+priming	O
+was	O
+examined	O
+by	O
+presenting	O
+an	O
+identity	O
+prime	O
+earlier	O
+in	O
+the	O
+text	O
+.	O
+
+METHODS	O
+:	O
+Forty	O
+-	O
+nine	O
+cases	O
+with	O
+intrahepatic	O
+multiple	O
+nodules	O
+of	O
+HCC	O
+,	O
+by	O
+gross	O
+examination	O
+,	O
+among	O
+184	O
+consecutive	O
+resected	O
+HCCs	O
+were	O
+examined	O
+clinicopathologically	O
+.	O
+
+In	O
+the	O
+present	O
+report	O
+,	O
+66	O
+hemochromatosis	O
+families	O
+yielding	O
+151	O
+hemochromatosis	O
+chromosomes	O
+and	O
+182	O
+normal	O
+chromosomes	O
+were	O
+RFLP	O
+-	O
+typed	O
+with	O
+a	O
+battery	O
+of	O
+probes	O
+,	O
+including	O
+two	O
+newly	O
+derived	O
+polymorphic	O
+markers	O
+from	O
+the	O
+6	O
+.	O
+7	O
+and	O
+HLA	B-GENE
+-	I-GENE
+F	I-GENE
+loci	I-GENE
+located	O
+150	O
+and	O
+250	O
+kb	O
+telomeric	O
+to	O
+HLA	B-GENE
+-	I-GENE
+A	I-GENE
+,	O
+respectively	O
+.	O
+
+Pneumothorax	O
+during	O
+laparoscopic	O
+dissection	O
+of	O
+the	O
+diaphragmatic	O
+hiatus	O
+.	O
+
+Different	O
+cortical	O
+malformations	O
+were	O
+produced	O
+in	O
+rats	O
+by	O
+a	O
+single	O
+dose	O
+of	O
+X	O
+-	O
+rays	O
+(	O
+200	O
+cGy	O
+)	O
+given	O
+on	O
+different	O
+days	O
+during	O
+gestation	O
+.	O
+
+T2	O
+cancers	O
+should	O
+not	O
+be	O
+excluded	O
+from	O
+the	O
+benefit	O
+of	O
+preoperative	O
+irradiation	O
+.	O
+
+IFN	B-GENE
+alpha	I-GENE
+and	O
+IFN	B-GENE
+gamma	I-GENE
+inducibility	O
+is	O
+mediated	O
+by	O
+a	O
+single	O
+element	O
+:	O
+a	O
+high	O
+affinity	O
+,	O
+nearly	O
+palindromic	O
+version	O
+of	O
+the	O
+IFN	B-GENE
+gamma	I-GENE
+activation	I-GENE
+site	I-GENE
+(	O
+GAS	B-GENE
+)	O
+.	O
+
+Twenty	O
+-	O
+three	O
+sequence	O
+-	O
+tagged	O
+sites	O
+(	O
+STSs	O
+)	O
+were	O
+mapped	O
+within	O
+the	O
+contig	O
+,	O
+a	O
+density	O
+of	O
+approximately	O
+1	O
+per	O
+200	O
+kb	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+demonstrate	O
+that	O
+binding	O
+of	O
+the	O
+GA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+GABP	B-GENE
+)	O
+to	O
+ets	B-GENE
+sequence	I-GENE
+motifs	I-GENE
+within	O
+each	O
+repeated	O
+unit	O
+is	O
+required	O
+for	O
+transcriptional	O
+activation	O
+of	O
+the	O
+COXIV	B-GENE
+promoter	I-GENE
+.	O
+
+To	O
+gain	O
+further	O
+insight	O
+into	O
+the	O
+pathogenesis	O
+of	O
+the	O
+adult	O
+respiratory	O
+distress	O
+syndrome	O
+(	O
+ARDS	O
+)	O
+,	O
+the	O
+authors	O
+studied	O
+possible	O
+relationships	O
+among	O
+the	O
+activation	O
+status	O
+of	O
+circulating	O
+polymorphonuclear	O
+neutrophils	O
+(	O
+PMN	O
+)	O
+,	O
+cytokine	O
+levels	O
+,	O
+and	O
+the	O
+severity	O
+of	O
+lung	O
+injury	O
+in	O
+31	O
+patients	O
+:	O
+15	O
+with	O
+ARDS	O
+,	O
+9	O
+with	O
+severe	O
+pneumonia	O
+uncomplicated	O
+by	O
+ARDS	O
+,	O
+and	O
+7	O
+mechanically	O
+ventilated	O
+patients	O
+with	O
+neither	O
+ARDS	O
+nor	O
+pneumonia	O
+.	O
+
+Amiodarone	O
+,	O
+seldom	O
+used	O
+as	O
+first	O
+-	O
+line	O
+treatment	O
+,	O
+appears	O
+to	O
+be	O
+the	O
+most	O
+effective	O
+drug	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+dopamine	B-GENE
+receptor	I-GENE
+stimulation	O
+by	O
+different	O
+dopamine	O
+agonists	O
+produces	O
+a	O
+different	O
+pattern	O
+of	O
+effects	O
+on	O
+the	O
+characteristics	O
+of	O
+the	O
+reaction	O
+time	O
+response	O
+.	O
+
+Two	O
+experiments	O
+were	O
+conducted	O
+to	O
+study	O
+the	O
+vacuous	O
+jaw	O
+movements	O
+induced	O
+in	O
+rats	O
+by	O
+acute	O
+administration	O
+of	O
+the	O
+monoamine	O
+-	O
+depleting	O
+agent	O
+reserpine	O
+.	O
+
+Depletion	O
+of	O
+dopamine	O
+in	O
+the	O
+nucleus	O
+accumbens	O
+led	O
+to	O
+a	O
+dramatic	O
+shift	O
+in	O
+behavior	O
+in	O
+which	O
+there	O
+was	O
+a	O
+significant	O
+decrease	O
+in	O
+lever	O
+pressing	O
+but	O
+a	O
+significant	O
+increase	O
+in	O
+consumption	O
+of	O
+lab	O
+chow	O
+.	O
+
+We	O
+have	O
+investigated	O
+the	O
+influence	O
+of	O
+NaFe3	O
++	O
+EDTA	O
+,	O
+and	O
+of	O
+increasing	O
+dietary	O
+levels	O
+of	O
+Na2EDTA	O
+,	O
+on	O
+Zn	O
+,	O
+Cu	O
+and	O
+Ca	O
+metabolism	O
+in	O
+rats	O
+fed	O
+on	O
+Zn	O
+-	O
+sufficient	O
+and	O
+Zn	O
+-	O
+deficient	O
+soya	O
+-	O
+bean	O
+-	O
+isolate	O
+-	O
+based	O
+diets	O
+.	O
+
+Recovery	O
+of	O
+carbimazole	O
+-	O
+induced	O
+agranulocytosis	O
+following	O
+recombinant	B-GENE
+granulocyte	I-GENE
+-	I-GENE
+macrophage	I-GENE
+colony	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+rhGM	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+administration	O
+.	O
+
+Thus	O
+,	O
+the	O
+system	O
+can	O
+be	O
+used	O
+to	O
+detect	O
+and	O
+study	O
+dynamic	O
+perfusion	O
+changes	O
+from	O
+the	O
+brain	O
+surface	O
+with	O
+minimal	O
+tissue	O
+damage	O
+.	O
+
+The	O
+neglect	O
+of	O
+Richards	O
+'	O
+s	O
+theory	O
+demonstrates	O
+the	O
+range	O
+of	O
+factors	O
+,	O
+other	O
+than	O
+the	O
+strictly	O
+scientific	O
+,	O
+which	O
+can	O
+be	O
+important	O
+in	O
+determining	O
+the	O
+influence	O
+or	O
+otherwise	O
+of	O
+a	O
+psychological	O
+theory	O
+.	O
+
+The	O
+positive	O
+-	O
+acting	O
+global	O
+sulfur	O
+regulatory	O
+protein	O
+,	O
+CYS3	B-GENE
+,	O
+of	O
+Neurospora	O
+crassa	O
+turns	O
+on	O
+the	O
+expression	O
+of	O
+a	O
+family	O
+of	O
+unlinked	O
+structural	O
+genes	O
+that	O
+encode	O
+enzymes	O
+of	O
+sulfur	O
+catabolism	O
+.	O
+
+Analysis	O
+of	O
+the	O
+upstream	O
+untranslated	O
+region	O
+of	O
+CHL15	B-GENE
+revealed	O
+the	O
+presence	O
+of	O
+the	O
+hexamer	O
+element	O
+,	O
+ACGCGT	O
+(	O
+an	O
+MluI	B-GENE
+restriction	I-GENE
+site	I-GENE
+)	O
+controlling	O
+both	O
+the	O
+periodic	O
+expression	O
+and	O
+coordinate	O
+regulation	O
+of	O
+the	O
+DNA	O
+synthesis	O
+genes	O
+in	O
+budding	O
+yeast	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+150	O
+-	O
+kDa	O
+protein	O
+contains	O
+an	O
+NTP	O
+-	O
+binding	O
+helicase	B-GENE
+motif	I-GENE
+and	O
+the	O
+readthrough	O
+region	O
+,	O
+an	O
+RNA	B-GENE
+polymerase	I-GENE
+motif	I-GENE
+,	O
+indicating	O
+that	O
+these	O
+two	O
+overlapping	O
+proteins	O
+may	O
+form	O
+an	O
+RNA	O
+replication	O
+complex	O
+similar	O
+to	O
+those	O
+of	O
+tobamo	O
+-	O
+and	O
+tobraviruses	O
+.	O
+
+On	O
+T2	O
+weighted	O
+images	O
+,	O
+low	O
+intensity	O
+areas	O
+in	O
+the	O
+thalamus	O
+,	O
+the	O
+striatum	O
+,	O
+the	O
+anterior	O
+limb	O
+of	O
+the	O
+internal	O
+capsule	O
+,	O
+the	O
+tegmentum	O
+of	O
+midbrain	O
+,	O
+high	O
+intensity	O
+areas	O
+in	O
+middle	O
+cerebellar	O
+peduncle	O
+,	O
+the	O
+posterior	O
+limb	O
+of	O
+the	O
+internal	O
+capsule	O
+,	O
+the	O
+lateral	O
+part	O
+of	O
+the	O
+cerebral	O
+peduncle	O
+,	O
+and	O
+the	O
+cerebral	O
+white	O
+matter	O
+were	O
+noted	O
+.	O
+
+Using	O
+the	O
+rap1t	B-GENE
+alleles	I-GENE
+to	O
+generate	O
+wild	O
+-	O
+type	O
+cells	O
+differing	O
+only	O
+in	O
+telomere	O
+tract	O
+lengths	O
+,	O
+we	O
+also	O
+show	O
+that	O
+telomere	O
+position	O
+effects	O
+are	O
+highly	O
+sensitive	O
+to	O
+changes	O
+in	O
+the	O
+size	O
+(	O
+or	O
+structure	O
+)	O
+of	O
+the	O
+telomeric	O
+tract	O
+.	O
+
+Pronounced	O
+microangiopathy	O
+characterized	O
+by	O
+avascular	O
+fields	O
+,	O
+enlarged	O
+and	O
+tortuous	O
+capillaries	O
+and	O
+increased	O
+transcapillary	O
+diffusion	O
+of	O
+sodium	O
+fluorescein	O
+,	O
+was	O
+clearly	O
+demonstrable	O
+in	O
+the	O
+area	O
+of	O
+the	O
+nodules	O
+.	O
+
+Epigenetic	O
+switching	O
+of	O
+transcriptional	O
+states	O
+:	O
+cis	O
+-	O
+and	O
+trans	O
+-	O
+acting	O
+factors	O
+affecting	O
+establishment	O
+of	O
+silencing	O
+at	O
+the	O
+HMR	B-GENE
+locus	I-GENE
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+The	O
+two	O
+methods	O
+identify	O
+the	O
+same	O
+patients	O
+only	O
+if	O
+micturitional	O
+pressures	O
+are	O
+normal	O
+(	O
+40	O
+to	O
+60	O
+cmH2O	O
+)	O
+to	O
+high	O
+(	O
+over	O
+60	O
+cmH2O	O
+)	O
+and	O
+the	O
+Sussett	O
+formula	O
+is	O
+used	O
+with	O
+a	O
+higher	O
+(	O
+95th	O
+centile	O
+)	O
+cutoff	O
+.	O
+
+There	O
+was	O
+no	O
+clear	O
+correlation	O
+between	O
+the	O
+MFA	O
+and	O
+the	O
+severity	O
+of	O
+the	O
+UTS	O
+phenotype	O
+.	O
+
+Chicken	O
+sterol	B-GENE
+carrier	I-GENE
+protein	I-GENE
+2	I-GENE
+/	O
+sterol	B-GENE
+carrier	I-GENE
+protein	I-GENE
+x	I-GENE
+:	O
+cDNA	O
+cloning	O
+reveals	O
+evolutionary	O
+conservation	O
+of	O
+structure	O
+and	O
+regulated	O
+expression	O
+.	O
+
+The	O
+plasmatic	B-GENE
+albumin	I-GENE
+concentration	O
+(	O
+3	O
+.	O
+5	O
+-	O
+4	O
+.	O
+5	O
+g	O
+/	O
+dl	O
+)	O
+represents	O
+about	O
+60	O
+%	O
+of	O
+the	O
+total	O
+plasma	O
+protein	O
+.	O
+
+A	O
+single	O
+five	O
+minute	O
+period	O
+of	O
+rapid	O
+atrial	O
+pacing	O
+fails	O
+to	O
+limit	O
+infarct	O
+size	O
+in	O
+the	O
+in	O
+situ	O
+rabbit	O
+heart	O
+.	O
+
+Neither	O
+RD19	B-GENE
+nor	O
+RD21	B-GENE
+mRNA	I-GENE
+synthesis	O
+was	O
+responsive	O
+to	O
+cold	O
+or	O
+to	O
+heat	O
+stress	O
+.	O
+
+Previous	O
+studies	O
+indicated	O
+that	O
+the	O
+20S	B-GENE
+proteasome	I-GENE
+is	O
+a	O
+catalytic	O
+core	O
+of	O
+the	O
+26S	B-GENE
+proteolytic	I-GENE
+complex	I-GENE
+that	O
+possesses	O
+a	O
+latent	O
+multicatalytic	O
+proteinase	O
+activity	O
+and	O
+catalyzes	O
+an	O
+ATP	O
+-	O
+dependent	O
+,	O
+selective	O
+breakdown	O
+of	O
+proteins	O
+ligated	O
+to	O
+ubiquitin	B-GENE
+.	O
+
+The	O
+O2	O
+deficit	O
+was	O
+not	O
+related	O
+to	O
+blood	O
+lactate	O
+during	O
+submaximal	O
+exercise	O
+,	O
+muscle	O
+enzyme	O
+activity	O
+(	O
+citrate	B-GENE
+synthase	I-GENE
+,	O
+3	B-GENE
+-	I-GENE
+hydroxyacyl	I-GENE
+-	I-GENE
+CoA	I-GENE
+-	I-GENE
+dehydrogenase	I-GENE
+,	O
+lactate	B-GENE
+dehydrogenase	I-GENE
+)	O
+,	O
+number	O
+of	O
+muscle	O
+capillaries	O
+,	O
+%	O
+ST	O
+fibres	O
+or	O
+muscle	O
+buffer	O
+capacity	O
+.	O
+
+The	O
+sequence	O
+of	O
+the	O
+putative	O
+RBP1	B-GENE
+protein	I-GENE
+contains	O
+two	O
+copies	O
+of	O
+an	O
+RNA	O
+recognition	O
+motif	O
+,	O
+two	O
+glutamine	O
+stretches	O
+,	O
+an	O
+asparagine	O
+-	O
+rich	O
+region	O
+,	O
+a	O
+methionine	O
+-	O
+rich	O
+region	O
+,	O
+and	O
+two	O
+long	O
+potential	O
+alpha	O
+-	O
+helixes	O
+.	O
+
+One	O
+defective	O
+RNA	O
+with	O
+a	O
+large	O
+deletion	O
+in	O
+the	O
+p70	B-GENE
+coding	I-GENE
+region	I-GENE
+was	O
+able	O
+to	O
+replicate	O
+efficiently	O
+,	O
+both	O
+when	O
+inoculated	O
+with	O
+the	O
+helper	O
+genome	O
+and	O
+when	O
+inoculated	O
+with	O
+a	O
+second	O
+complementing	O
+defective	O
+RNA	O
+that	O
+supplied	O
+a	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+p70	I-GENE
+.	O
+
+Complete	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+bacteriophage	B-GENE
+K1F	I-GENE
+tail	I-GENE
+gene	I-GENE
+encoding	O
+endo	B-GENE
+-	I-GENE
+N	I-GENE
+-	I-GENE
+acylneuraminidase	I-GENE
+(	O
+endo	B-GENE
+-	I-GENE
+N	I-GENE
+)	O
+and	O
+comparison	O
+to	O
+an	O
+endo	B-GENE
+-	I-GENE
+N	I-GENE
+homolog	I-GENE
+in	O
+bacteriophage	O
+PK1E	O
+.	O
+
+Binding	O
+of	O
+U2	B-GENE
+small	I-GENE
+nuclear	I-GENE
+ribonucleoprotein	I-GENE
+was	O
+partially	O
+inhibited	O
+.	O
+
+Morphometrical	O
+quantification	O
+of	O
+brain	O
+edema	O
+related	O
+to	O
+experimental	O
+multiple	O
+micro	O
+-	O
+infarcts	O
+in	O
+mice	O
+:	O
+assessment	O
+of	O
+neurotropin	B-GENE
+effect	O
+.	O
+
+One	O
+member	O
+of	O
+this	O
+multigene	O
+family	O
+,	O
+GATA	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+is	O
+most	O
+abundantly	O
+expressed	O
+in	O
+T	O
+lymphocytes	O
+,	O
+a	O
+cellular	O
+target	O
+for	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+infection	O
+and	O
+replication	O
+.	O
+
+Indeed	O
+,	O
+significant	O
+level	O
+of	O
+CAT	B-GENE
+activity	O
+was	O
+observed	O
+in	O
+human	O
+lung	O
+adenocarcinoma	O
+(	O
+A549	O
+-	O
+1	O
+)	O
+cells	O
+which	O
+had	O
+been	O
+incubated	O
+with	O
+a	O
+complex	O
+of	O
+T7	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+,	O
+pT7	B-GENE
+-	I-GENE
+EMC	I-GENE
+-	I-GENE
+CAT	I-GENE
+DNA	I-GENE
+and	O
+DC	O
+-	O
+chol	O
+cationic	O
+liposomes	O
+.	O
+
+Pneumoscrotum	O
+is	O
+a	O
+rare	O
+condition	O
+that	O
+receives	O
+little	O
+discussion	O
+in	O
+standard	O
+texts	O
+of	O
+urology	O
+.	O
+
+The	O
+first	O
+gene	O
+codes	O
+for	O
+a	O
+protein	O
+containing	O
+11	O
+cystein	O
+residues	O
+in	O
+an	O
+arrangement	O
+typical	O
+for	O
+Fe	B-GENE
+/	I-GENE
+S	I-GENE
+proteins	I-GENE
+.	O
+
+Triton	O
+-	O
+disrupted	O
+cells	O
+retained	O
+capacity	O
+for	O
+activation	O
+of	O
+the	O
+pathway	O
+by	O
+both	O
+peptide	O
+growth	O
+factors	O
+and	O
+by	O
+addition	O
+of	O
+GTP	O
+-	O
+loaded	O
+p21	B-GENE
+rasVal12	B-GENE
+.	O
+
+To	O
+begin	O
+to	O
+examine	O
+the	O
+mechanism	O
+controlling	O
+expression	O
+of	O
+this	O
+gene	O
+during	O
+the	O
+cell	O
+-	O
+cycle	O
+,	O
+a	O
+mouse	B-GENE
+B	I-GENE
+-	I-GENE
+myb	I-GENE
+5	I-GENE
+'	I-GENE
+flanking	I-GENE
+sequence	I-GENE
+was	O
+isolated	O
+from	O
+a	O
+cosmid	O
+library	O
+and	O
+shown	O
+to	O
+promote	O
+efficiently	O
+the	O
+transcription	O
+of	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+when	O
+transfected	O
+into	O
+NIH3T3	O
+fibroblasts	O
+.	O
+
+The	O
+influence	O
+of	O
+a	O
+high	O
+ionic	O
+strength	O
+on	O
+the	O
+resolution	O
+was	O
+clearly	O
+shown	O
+.	O
+
+The	O
+number	O
+of	O
+bacteria	O
+in	O
+the	O
+lung	O
+,	O
+peripheral	O
+white	O
+blood	O
+cell	O
+and	O
+BAL	O
+fluid	O
+cell	O
+also	O
+decreased	O
+by	O
+the	O
+administration	O
+of	O
+FN	B-GENE
+.	O
+
+In	O
+mice	O
+,	O
+three	O
+major	O
+families	O
+of	O
+L1	O
+elements	O
+,	O
+termed	O
+"	O
+A	O
+,	O
+"	O
+"	O
+F	O
+,	O
+"	O
+and	O
+"	O
+V	O
+,	O
+"	O
+have	O
+been	O
+defined	O
+on	O
+the	O
+basis	O
+of	O
+the	O
+sequence	O
+found	O
+at	O
+the	O
+5	O
+'	O
+terminus	O
+.	O
+
+TFEC	B-GENE
+,	O
+a	O
+basic	B-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+protein	I-GENE
+,	O
+forms	O
+heterodimers	O
+with	O
+TFE3	B-GENE
+and	O
+inhibits	O
+TFE3	B-GENE
+-	O
+dependent	O
+transcription	O
+activation	O
+.	O
+
+Similar	O
+results	O
+were	O
+seen	O
+on	O
+Western	O
+blots	O
+of	O
+Autographa	O
+californica	O
+MNPV	O
+(	O
+AcMNPV	O
+)	O
+-	O
+infected	O
+Spodoptera	O
+frugiperda	O
+cells	O
+.	O
+
+In	O
+infected	O
+mammalian	O
+cells	O
+,	O
+the	O
+ARV	B-GENE
+G	I-GENE
+and	O
+GNS	B-GENE
+genes	I-GENE
+are	O
+transcribed	O
+primarily	O
+as	O
+a	O
+polycistronic	O
+mRNA	O
+which	O
+appears	O
+to	O
+extend	O
+from	O
+the	O
+consensus	O
+sequence	O
+(	O
+AACAG	O
+)	O
+at	O
+the	O
+start	O
+of	O
+the	O
+G	B-GENE
+gene	I-GENE
+to	O
+the	O
+next	O
+recognized	O
+polyadenylation	O
+signal	O
+(	O
+CATG	O
+[	O
+A	O
+]	O
+7	O
+)	O
+located	O
+697	O
+nucleotides	O
+downstream	O
+of	O
+the	O
+GNS	B-GENE
+protein	I-GENE
+termination	O
+codon	O
+.	O
+
+Molecular	O
+cloning	O
+and	O
+expression	O
+of	O
+RPE65	B-GENE
+,	O
+a	O
+novel	O
+retinal	O
+pigment	O
+epithelium	O
+-	O
+specific	O
+microsomal	O
+protein	O
+that	O
+is	O
+post	O
+-	O
+transcriptionally	O
+regulated	O
+in	O
+vitro	O
+.	O
+
+The	O
+mean	O
+power	O
+(	O
+in	O
+mu	O
+W	O
+)	O
+required	O
+to	O
+produce	O
+the	O
+observed	O
+flow	O
+rate	O
+was	O
+estimated	O
+at	O
+each	O
+outflow	O
+pressure	O
+as	O
+the	O
+product	O
+of	O
+the	O
+flow	O
+rate	O
+and	O
+the	O
+pressure	O
+across	O
+the	O
+lymphatic	O
+vessel	O
+.	O
+
+Although	O
+antisperm	O
+antibodies	O
+are	O
+associated	O
+with	O
+infertility	O
+,	O
+many	O
+hospital	O
+laboratories	O
+do	O
+not	O
+test	O
+for	O
+these	O
+antibodies	O
+.	O
+
+PPD	B-GENE
+-	O
+specific	O
+IgG	B-GENE
+subclass	O
+responses	O
+were	O
+evident	O
+to	O
+all	O
+four	O
+IgG	B-GENE
+subclasses	O
+.	O
+
+Anterior	O
+body	O
+pattern	O
+in	O
+Drosophila	O
+is	O
+specified	O
+by	O
+the	O
+graded	O
+distribution	O
+of	O
+the	O
+bicoid	B-GENE
+protein	I-GENE
+(	O
+bcd	B-GENE
+)	O
+,	O
+which	O
+activates	O
+subordinate	O
+genes	O
+in	O
+distinct	O
+anterior	O
+domains	O
+.	O
+
+GAP	B-GENE
+-	I-GENE
+N	I-GENE
+bound	O
+constitutively	O
+to	O
+p190	B-GENE
+in	O
+both	O
+serum	O
+-	O
+deprived	O
+and	O
+growth	O
+factor	O
+-	O
+stimulated	O
+cells	O
+.	O
+
+The	O
+peptide	O
+sequence	O
+contains	O
+a	O
+region	O
+of	O
+80	O
+amino	O
+acids	O
+that	O
+shows	O
+similarity	O
+to	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+to	O
+the	O
+recently	O
+described	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+related	I-GENE
+gene	I-GENE
+,	O
+MCL1	B-GENE
+.	O
+
+The	O
+phosphorylation	O
+efficiency	O
+is	O
+improved	O
+by	O
+increasing	O
+the	O
+number	O
+of	O
+N	O
+-	O
+terminal	O
+arginine	O
+residues	O
+and	O
+by	O
+moving	O
+the	O
+arginyl	O
+cluster	O
+one	O
+residue	O
+further	O
+away	O
+from	O
+the	O
+serine	O
+,	O
+the	O
+nonapeptide	O
+(	O
+Arg	O
+)	O
+4	O
+-	O
+Ala	O
+-	O
+Ala	O
+-	O
+Ser	O
+-	O
+Val	O
+-	O
+Ala	O
+being	O
+the	O
+best	O
+substrate	O
+among	O
+all	O
+the	O
+short	O
+peptides	O
+tested	O
+(	O
+Km	O
+=	O
+15	O
+microM	O
+)	O
+.	O
+
+The	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+GAL1	I-GENE
+and	O
+GAL10	B-GENE
+genes	I-GENE
+are	O
+controlled	O
+in	O
+response	O
+to	O
+the	O
+availability	O
+of	O
+galactose	O
+and	O
+glucose	O
+by	O
+multiple	O
+activating	O
+and	O
+repressing	O
+proteins	O
+bound	O
+at	O
+adjacent	O
+or	O
+overlapping	O
+sites	O
+in	O
+UASG	O
+.	O
+
+Surprisingly	O
+,	O
+the	O
+results	O
+of	O
+several	O
+experiments	O
+suggest	O
+that	O
+the	O
+TSF	B-GENE
+genes	I-GENE
+encode	O
+global	O
+regulatory	O
+factors	O
+.	O
+tsf1	B-GENE
+to	O
+tsf6	B-GENE
+mutations	O
+derepressed	O
+expression	O
+from	O
+yeast	O
+CYC	B-GENE
+-	O
+GAL	B-GENE
+hybrid	O
+promoters	O
+(	O
+fused	O
+to	O
+lacZ	B-GENE
+)	O
+that	O
+harbor	O
+a	O
+variety	O
+of	O
+operator	O
+sequences	O
+,	O
+and	O
+caused	O
+pleiotropic	O
+defects	O
+in	O
+cell	O
+growth	O
+,	O
+mating	O
+,	O
+and	O
+sporulation	O
+.	O
+
+Sex	O
+of	O
+calf	O
+(	O
+variate	O
+2	O
+)	O
+was	O
+associated	O
+most	O
+closely	O
+with	O
+width	O
+of	O
+muzzle	O
+and	O
+head	O
+.	O
+
+Sequence	O
+comparison	O
+indicates	O
+that	O
+exons	O
+5	O
+'	O
+/	O
+L	O
+and	O
+L	O
+/	O
+N	O
+in	O
+PSG12	B-GENE
+and	O
+PSG12	B-GENE
+psi	I-GENE
+are	O
+99	O
+%	O
+identical	O
+,	O
+except	O
+that	O
+the	O
+L	O
+/	O
+N	O
+exon	O
+in	O
+the	O
+PSG12	B-GENE
+psi	I-GENE
+gene	I-GENE
+contains	O
+a	O
+stop	O
+codon	O
+.	O
+
+The	O
+mechanisms	O
+that	O
+govern	O
+the	O
+activation	O
+or	O
+suppression	O
+of	O
+the	O
+CD8	B-GENE
+gene	I-GENE
+are	O
+likely	O
+to	O
+be	O
+central	O
+to	O
+the	O
+T	O
+cell	O
+development	O
+program	O
+.	O
+
+We	O
+suggest	O
+that	O
+the	O
+ER	O
+lumenal	O
+variable	O
+domain	O
+of	O
+gp19K	B-GENE
+has	O
+a	O
+specific	O
+tertiary	O
+structure	O
+that	O
+is	O
+important	O
+for	O
+binding	O
+to	O
+the	O
+polymorphic	O
+alpha	O
+1	O
+and	O
+alpha	O
+2	O
+domains	O
+of	O
+class	B-GENE
+I	I-GENE
+heavy	I-GENE
+(	I-GENE
+alpha	I-GENE
+)	I-GENE
+chains	I-GENE
+.	O
+
+We	O
+recently	O
+found	O
+that	O
+17	O
+beta	O
+-	O
+estradiol	O
+(	O
+E2	O
+)	O
+not	O
+only	O
+suppresses	O
+bone	O
+resorption	O
+but	O
+also	O
+stimulates	O
+bone	O
+formation	O
+in	O
+the	O
+cancellous	O
+bone	O
+of	O
+female	O
+rats	O
+.	O
+
+Recombinant	B-GENE
+human	I-GENE
+erythropoietin	I-GENE
+(	O
+epoetin	B-GENE
+)	O
+is	O
+approved	O
+to	O
+be	O
+administered	O
+by	O
+the	O
+intravenous	O
+(	O
+i	O
+.	O
+v	O
+.	O
+)	O
+or	O
+subcutaneous	O
+(	O
+SC	O
+)	O
+route	O
+.	O
+
+Single	O
+-	O
+photon	O
+emission	O
+computed	O
+tomography	O
+(	O
+SPECT	O
+)	O
+with	O
+99mTc	O
+-	O
+hexamethylpropyleneamine	O
+oxime	O
+(	O
+HMPAO	O
+)	O
+was	O
+used	O
+to	O
+investigate	O
+changes	O
+in	O
+cerebral	O
+blood	O
+flow	O
+in	O
+seven	O
+patients	O
+with	O
+cortical	O
+visual	O
+impairment	O
+.	O
+
+The	O
+rCBF	O
+ratio	O
+was	O
+mainly	O
+reduced	O
+in	O
+frontal	O
+lobes	O
+(	O
+65	O
+%	O
+)	O
+.	O
+
+METHODS	O
+:	O
+Twenty	O
+-	O
+two	O
+patients	O
+were	O
+grouped	O
+according	O
+to	O
+their	O
+etiology	O
+based	O
+on	O
+the	O
+study	O
+of	O
+antiadrenal	O
+antibodies	O
+at	O
+diagnosis	O
+of	O
+the	O
+disease	O
+:	O
+7	O
+were	O
+positive	O
+(	O
+autoimmune	O
+etiology	O
+or	O
+EAA	O
+)	O
+,	O
+11	O
+were	O
+negative	O
+(	O
+tuberculous	O
+etiology	O
+or	O
+EAT	O
+)	O
+and	O
+in	O
+four	O
+serologic	O
+study	O
+was	O
+not	O
+available	O
+(	O
+undetermined	O
+etiology	O
+or	O
+EAI	O
+)	O
+.	O
+
+The	O
+UV	O
+induction	O
+of	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+is	O
+mediated	O
+by	O
+two	O
+UV	O
+response	O
+elements	O
+consisting	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+like	I-GENE
+sequences	I-GENE
+within	O
+its	O
+5	O
+'	O
+control	O
+region	O
+.	O
+
+Protein	B-GENE
+tyrosine	I-GENE
+phosphatases	I-GENE
+(	O
+PTPs	B-GENE
+)	O
+,	O
+together	O
+with	O
+protein	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+(	O
+PTKs	B-GENE
+)	O
+,	O
+are	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+cell	O
+activation	O
+,	O
+growth	O
+,	O
+and	O
+differentiation	O
+.	O
+
+ST	O
+elevation	O
+occurs	O
+in	O
+5	O
+patients	O
+(	O
+55	O
+.	O
+5	O
+%	O
+)	O
+of	O
+subgroup	O
+A	O
+and	O
+in	O
+no	O
+patient	O
+of	O
+the	O
+subgroup	O
+B	O
+.	O
+
+Furthermore	O
+,	O
+a	O
+p21X	B-GENE
+protein	I-GENE
+lacking	O
+the	O
+N	O
+-	O
+terminus	O
+of	O
+Rex1	B-GENE
+was	O
+expressed	O
+at	O
+high	O
+levels	O
+;	O
+our	O
+data	O
+indicate	O
+that	O
+p21X	B-GENE
+is	O
+translated	O
+from	O
+the	O
+1	O
+.	O
+6	O
+-	O
+kb	O
+mRNA	O
+which	O
+is	O
+derived	O
+primarily	O
+from	O
+deleted	O
+proviruses	O
+.	O
+
+HTLV	O
+-	O
+1	O
+gene	O
+expression	O
+by	O
+defective	O
+proviruses	O
+in	O
+an	O
+infected	O
+T	O
+-	O
+cell	O
+line	O
+.	O
+
+Thus	O
+,	O
+it	O
+was	O
+confirmed	O
+that	O
+the	O
+sodium	O
+lauryl	O
+sulfate	O
+method	O
+of	O
+estimating	O
+hemoglobin	B-GENE
+concentration	O
+is	O
+an	O
+appropriate	O
+alternative	O
+to	O
+the	O
+cyanmethemoglobin	B-GENE
+method	O
+and	O
+avoids	O
+the	O
+generation	O
+of	O
+toxic	O
+wastes	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+predicted	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+two	O
+human	B-GENE
+PKC	I-GENE
+-	I-GENE
+delta	I-GENE
+clones	O
+with	O
+the	O
+rat	O
+and	O
+mouse	O
+homologues	O
+indicated	O
+a	O
+greater	O
+degree	O
+of	O
+sequence	O
+divergence	O
+(	O
+89	O
+-	O
+90	O
+%	O
+homology	O
+)	O
+compared	O
+to	O
+the	O
+high	O
+degree	O
+of	O
+sequence	O
+conservation	O
+observed	O
+with	O
+other	O
+human	B-GENE
+PKC	I-GENE
+family	I-GENE
+members	I-GENE
+and	O
+their	O
+mammalian	O
+counterparts	O
+.	O
+
+XII	O
+.	O
+
+When	O
+comparing	O
+the	O
+barley	B-GENE
+PSI	I-GENE
+-	I-GENE
+K	I-GENE
+and	O
+PSI	B-GENE
+-	I-GENE
+G	I-GENE
+with	O
+the	O
+reported	O
+PSI	B-GENE
+-	I-GENE
+K	I-GENE
+sequence	I-GENE
+from	I-GENE
+Synechococcus	I-GENE
+vulcanus	I-GENE
+,	O
+the	O
+degree	O
+of	O
+similarity	O
+is	O
+equal	O
+,	O
+suggesting	O
+that	O
+an	O
+ancestral	O
+gene	O
+has	O
+been	O
+duplicated	O
+in	O
+a	O
+chloroplast	O
+progenitor	O
+but	O
+not	O
+in	O
+a	O
+cyanobacterial	O
+.	O
+
+Under	O
+these	O
+conditions	O
+,	O
+transfections	O
+with	O
+cDNAs	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+p50	B-GENE
+and	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+(	O
+SRF	B-GENE
+)	O
+produced	O
+a	O
+factor	O
+(	O
+s	O
+)	O
+that	O
+mediated	O
+Tax	B-GENE
+binding	O
+to	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+site	I-GENE
+and	O
+the	O
+CArG	O
+box	O
+respectively	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+v	B-GENE
+-	I-GENE
+Rel	I-GENE
+specifically	O
+increased	O
+expression	O
+from	O
+a	O
+reporter	O
+plasmid	O
+containing	O
+multiple	O
+Sp1	B-GENE
+binding	I-GENE
+sites	I-GENE
+approximately	O
+sixfold	O
+in	O
+chicken	O
+embryo	O
+fibroblasts	O
+(	O
+CEFs	O
+)	O
+,	O
+even	O
+though	O
+v	B-GENE
+-	I-GENE
+Rel	I-GENE
+did	O
+not	O
+bind	O
+directly	O
+to	O
+these	O
+sites	O
+.	O
+v	B-GENE
+-	I-GENE
+Rel	I-GENE
+also	O
+increased	O
+expression	O
+from	O
+a	O
+reporter	O
+plasmid	O
+containing	O
+a	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+(	O
+LTR	O
+)	O
+in	O
+which	O
+the	O
+kappa	B-GENE
+B	I-GENE
+binding	I-GENE
+sites	I-GENE
+were	O
+mutated	O
+but	O
+which	O
+still	O
+contained	O
+intact	O
+Sp1	B-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+The	O
+simultaneous	O
+recording	O
+of	O
+electrical	O
+activity	O
+from	O
+the	O
+surface	O
+electrocardiogram	O
+,	O
+right	O
+ventricular	O
+apex	O
+,	O
+His	O
+bundle	O
+,	O
+high	O
+right	O
+atrium	O
+,	O
+coronary	O
+sinus	O
+,	O
+with	O
+or	O
+without	O
+a	O
+roving	O
+mapping	O
+catheter	O
+,	O
+enables	O
+us	O
+to	O
+precisely	O
+map	O
+the	O
+electrical	O
+activation	O
+sequence	O
+in	O
+the	O
+heart	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+retrospective	O
+analysis	O
+does	O
+not	O
+confirm	O
+the	O
+efficacy	O
+of	O
+one	O
+course	O
+of	O
+simultaneous	O
+Mitomycin	O
+-	O
+C	O
+and	O
+5	O
+-	O
+fluorouracil	O
+,	O
+at	O
+least	O
+in	O
+association	O
+with	O
+full	O
+-	O
+dose	O
+radiotherapy	O
+incorporating	O
+Iridium	O
+-	O
+192	O
+boost	O
+.	O
+
+Despite	O
+the	O
+existence	O
+of	O
+30	O
+cysteine	O
+residues	O
+,	O
+carboxymethylation	O
+prevented	O
+the	O
+formation	O
+of	O
+most	O
+if	O
+not	O
+all	O
+disulfide	O
+bonds	O
+that	O
+otherwise	O
+occurred	O
+when	O
+the	O
+cells	O
+were	O
+sonicated	O
+.	O
+
+Cerebro	O
+-	O
+oculo	O
+-	O
+facioskeletal	O
+syndrome	O
+(	O
+Pena	O
+-	O
+Shokeir	O
+syndrome	O
+II	O
+)	O
+
+Most	O
+importantly	O
+,	O
+the	O
+addition	O
+of	O
+purified	O
+17S	B-GENE
+U2	I-GENE
+snRNPs	I-GENE
+,	O
+but	O
+not	O
+of	O
+12S	B-GENE
+U2	I-GENE
+snRNPs	I-GENE
+,	O
+to	O
+HeLa	O
+splicing	O
+extracts	O
+in	O
+which	O
+the	O
+endogeneous	B-GENE
+U2	I-GENE
+snRNPs	I-GENE
+have	O
+been	O
+functionally	O
+neutralized	O
+with	O
+anti	B-GENE
+-	I-GENE
+PRP9	I-GENE
+antibodies	I-GENE
+fully	O
+restores	O
+the	O
+mRNA	O
+-	O
+splicing	O
+activity	O
+of	O
+the	O
+extracts	O
+.	O
+
+Differences	O
+in	O
+profiles	O
+of	O
+viscosity	O
+variables	O
+between	O
+subgroups	O
+of	O
+EAD	O
+in	O
+RA	O
+patients	O
+were	O
+observed	O
+.	O
+
+These	O
+contain	O
+a	O
+single	O
+1977	O
+-	O
+bp	O
+exon	O
+that	O
+encodes	O
+900	O
+bp	O
+of	O
+the	O
+5	O
+'	O
+and	O
+3	O
+'	O
+untranslated	O
+sequences	O
+in	O
+addition	O
+to	O
+a	O
+1077	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+identical	O
+to	O
+that	O
+found	O
+in	O
+vascular	B-GENE
+smooth	I-GENE
+muscle	I-GENE
+cell	I-GENE
+AT1a	I-GENE
+receptor	I-GENE
+cDNAs	I-GENE
+.	O
+
+Deletion	O
+of	O
+a	O
+53	O
+-	O
+bp	O
+early	O
+promoter	O
+region	O
+containing	O
+the	O
+transcription	O
+start	O
+site	O
+and	O
+a	O
+putative	O
+TATA	O
+box	O
+completely	O
+abolishes	O
+the	O
+ability	O
+of	O
+upstream	O
+elements	O
+to	O
+drive	O
+transcription	O
+of	O
+the	O
+luciferase	B-GENE
+cDNA	I-GENE
+.	O
+
+One	O
+chimpanzee	O
+reliably	O
+selected	O
+the	O
+larger	O
+numeral	O
+4	O
+during	O
+testing	O
+with	O
+a	O
+nonadjacent	O
+pair	O
+(	O
+2	O
+-	O
+4	O
+)	O
+,	O
+and	O
+2	O
+chimps	O
+showed	O
+no	O
+preference	O
+.	O
+
+Dissipation	O
+of	O
+claudication	O
+pain	O
+after	O
+walking	O
+:	O
+implications	O
+for	O
+endurance	O
+training	O
+.	O
+
+Alternative	O
+transcript	O
+of	O
+the	O
+nonselective	O
+-	O
+type	O
+endothelin	B-GENE
+receptor	I-GENE
+from	O
+rat	O
+brain	O
+.	O
+
+The	O
+Drosophila	O
+clathrin	B-GENE
+heavy	I-GENE
+chain	I-GENE
+gene	O
+:	O
+clathrin	B-GENE
+function	O
+is	O
+essential	O
+in	O
+a	O
+multicellular	O
+organism	O
+.	O
+
+The	O
+binding	O
+specificity	O
+of	O
+this	O
+protein	O
+was	O
+compared	O
+to	O
+that	O
+of	O
+human	B-GENE
+E2F	I-GENE
+using	O
+a	O
+number	O
+of	O
+mutant	B-GENE
+E2F	I-GENE
+sites	I-GENE
+as	O
+competitors	O
+.	O
+
+To	O
+analyze	O
+the	O
+VH	O
+regions	O
+of	O
+polyreactive	O
+antibodies	O
+,	O
+with	O
+particular	O
+attention	O
+at	O
+their	O
+somatically	O
+mutated	O
+status	O
+,	O
+we	O
+generated	O
+five	O
+IgG	B-GENE
+(	O
+three	O
+IgG1	B-GENE
+and	O
+two	O
+IgG3	B-GENE
+)	O
+mAb	O
+(	O
+using	O
+B	O
+cells	O
+from	O
+a	O
+healthy	O
+subject	O
+,	O
+a	O
+patient	O
+with	O
+insulin	B-GENE
+-	O
+dependent	O
+diabetes	O
+mellitus	O
+and	O
+a	O
+patient	O
+with	O
+SLE	O
+)	O
+,	O
+which	O
+bound	O
+with	O
+various	O
+efficiencies	O
+a	O
+number	O
+of	O
+different	O
+self	O
+and	O
+foreign	O
+Ag	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+the	O
+patch	O
+determines	O
+the	O
+proper	O
+conformation	O
+of	O
+the	O
+site	O
+and	O
+thereby	O
+contributes	O
+to	O
+recognition	O
+indirectly	O
+.	O
+
+The	O
+7	O
+-	O
+kb	O
+mRNA	O
+differs	O
+by	O
+alternative	O
+splicing	O
+such	O
+that	O
+it	O
+encodes	O
+a	O
+protein	O
+with	O
+a	O
+distinct	O
+amino	O
+terminus	O
+.	O
+
+Kinetics	O
+of	O
+the	O
+inhibition	O
+indicated	O
+that	O
+this	O
+polymerase	O
+domain	O
+can	O
+inhibit	O
+viral	O
+replication	O
+only	O
+during	O
+the	O
+preinitiation	O
+stage	O
+.	O
+
+3	O
+.	O
+
+McCann	O
+III	O
+,	O
+F	O
+.	O
+
+In	O
+order	O
+to	O
+investigate	O
+to	O
+what	O
+extent	O
+this	O
+interaction	O
+might	O
+contribute	O
+to	O
+tumor	O
+induction	O
+by	O
+the	O
+virus	O
+,	O
+we	O
+have	O
+introduced	O
+two	O
+different	O
+point	O
+mutations	O
+within	O
+the	O
+putative	O
+pRb	B-GENE
+-	I-GENE
+binding	I-GENE
+sequence	I-GENE
+of	O
+large	B-GENE
+T	I-GENE
+antigen	I-GENE
+,	O
+and	O
+as	O
+a	O
+preliminary	O
+to	O
+in	O
+vivo	O
+experiments	O
+we	O
+have	O
+studied	O
+their	O
+effects	O
+in	O
+vitro	O
+on	O
+some	O
+biological	O
+activities	O
+relevant	O
+to	O
+tumor	O
+induction	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+conservation	O
+of	O
+nucleotides	O
+154	O
+to	O
+156	O
+is	O
+likely	O
+to	O
+be	O
+a	O
+consequence	O
+of	O
+their	O
+role	O
+as	O
+a	O
+sequence	O
+-	O
+specific	O
+recognition	O
+element	O
+for	O
+the	O
+SRP54	B-GENE
+protein	I-GENE
+.	O
+
+A	O
+region	O
+of	O
+the	O
+deduced	O
+protein	O
+shares	O
+extensive	O
+homology	O
+with	O
+a	O
+catalytic	O
+region	O
+of	O
+Raf	B-GENE
+kinases	I-GENE
+,	O
+a	O
+feature	O
+shared	O
+only	O
+with	O
+TFIIE	B-GENE
+among	O
+transcription	O
+factors	O
+.	O
+
+The	O
+low	O
+molecular	O
+mass	O
+polypeptide	O
+complex	O
+is	O
+assumed	O
+to	O
+be	O
+involved	O
+in	O
+antigen	O
+presentation	O
+,	O
+generating	O
+peptides	O
+from	O
+cytosolic	O
+protein	O
+antigens	O
+,	O
+which	O
+are	O
+subsequently	O
+presented	O
+to	O
+cytotoxic	O
+T	O
+-	O
+lymphocytes	O
+on	O
+the	O
+cell	O
+surface	O
+.	O
+
+Secondary	O
+cleavage	O
+of	O
+RT	B-GENE
+at	O
+Trp	O
+-	O
+595	O
+-	O
+Tyr	O
+-	O
+596	O
+of	O
+Pol	B-GENE
+yields	O
+a	O
+truncated	O
+form	O
+lacking	O
+the	O
+C	B-GENE
+-	I-GENE
+terminal	I-GENE
+RNase	I-GENE
+H	I-GENE
+domain	I-GENE
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+approximately	O
+50	O
+amino	O
+acids	O
+of	O
+Bel	B-GENE
+-	I-GENE
+1	I-GENE
+are	O
+shown	O
+to	O
+be	O
+essential	O
+for	O
+Bel	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+but	O
+can	O
+be	O
+effectively	O
+substituted	O
+by	O
+the	O
+C	O
+-	O
+terminal	O
+activation	O
+domain	O
+of	O
+VP16	B-GENE
+.	O
+
+Since	O
+the	O
+-	O
+172	O
+/	O
+-	O
+148	O
+element	O
+also	O
+conferred	O
+estrogen	O
+and	O
+thyroid	O
+hormone	O
+responsiveness	O
+,	O
+it	O
+can	O
+be	O
+considered	O
+a	O
+composite	O
+hormone	O
+response	O
+element	O
+.	O
+
+Optimal	O
+activation	O
+of	O
+T	O
+cells	O
+requires	O
+at	O
+least	O
+two	O
+signals	O
+.	O
+
+Together	O
+with	O
+a	O
+considerably	O
+shortened	O
+and	O
+interrupted	O
+aromatic	O
+aa	O
+stretch	O
+in	O
+this	O
+region	O
+,	O
+these	O
+differences	O
+are	O
+discussed	O
+in	O
+terms	O
+of	O
+the	O
+peculiar	O
+affinity	O
+of	O
+cyanobacterial	B-GENE
+cytochrome	I-GENE
+oxidases	I-GENE
+for	O
+acidic	O
+c	B-GENE
+-	I-GENE
+type	I-GENE
+cytochromes	I-GENE
+.	O
+
+All	O
+four	O
+of	O
+the	O
+genes	O
+have	O
+a	O
+similar	O
+structure	O
+,	O
+with	O
+the	O
+receptor	O
+protein	O
+encoded	O
+in	O
+a	O
+single	O
+exon	O
+.	O
+
+Identity	O
+of	O
+GABP	B-GENE
+with	O
+NRF	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+a	O
+multisubunit	O
+activator	O
+of	O
+cytochrome	B-GENE
+oxidase	I-GENE
+expression	O
+,	O
+reveals	O
+a	O
+cellular	O
+role	O
+for	O
+an	O
+ETS	B-GENE
+domain	I-GENE
+activator	O
+of	O
+viral	O
+promoters	O
+.	O
+
+The	O
+intracellular	O
+basic	B-GENE
+region	I-GENE
+/	I-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+(	I-GENE
+bHLH	I-GENE
+)	I-GENE
+dioxin	I-GENE
+receptor	I-GENE
+mediates	O
+signal	O
+transduction	O
+by	O
+dioxin	O
+(	O
+2	O
+,	O
+3	O
+,	O
+7	O
+,	O
+8	O
+-	O
+tetrachlorodibenzo	O
+-	O
+p	O
+-	O
+dioxin	O
+)	O
+and	O
+functions	O
+as	O
+a	O
+ligand	O
+-	O
+activated	O
+DNA	O
+binding	O
+protein	O
+directly	O
+interacting	O
+with	O
+target	O
+genes	O
+by	O
+binding	O
+to	O
+dioxin	O
+response	O
+elements	O
+.	O
+
+The	O
+alpha	B-GENE
+2A	I-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptor	I-GENE
+(	O
+alpha	B-GENE
+2AAR	I-GENE
+)	O
+is	O
+coupled	O
+to	O
+a	O
+variety	O
+of	O
+effectors	O
+via	O
+pertussis	B-GENE
+toxin	I-GENE
+-	O
+sensitive	O
+GTP	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+.	O
+
+A	O
+sequence	O
+comparison	O
+reveals	O
+two	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+)	O
+consensus	O
+sequences	O
+,	O
+basic	O
+DNA	O
+binding	O
+region	O
+and	O
+leucine	O
+zippers	O
+1	O
+and	O
+2	O
+(	O
+bZIP1	O
+and	O
+bZIP2	O
+)	O
+,	O
+within	O
+this	O
+region	O
+.	O
+
+One	O
+of	O
+these	O
+genes	O
+,	O
+REC114	B-GENE
+,	O
+is	O
+described	O
+here	O
+,	O
+and	O
+the	O
+data	O
+confirm	O
+that	O
+REC114	B-GENE
+is	O
+a	O
+meiosis	O
+-	O
+specific	O
+recombination	O
+gene	O
+with	O
+no	O
+detectable	O
+function	O
+in	O
+mitosis	O
+.	O
+
+The	O
+transactivation	O
+function	O
+of	O
+EBNA2	B-GENE
+was	O
+also	O
+observed	O
+in	O
+the	O
+HeLa	O
+epithelial	O
+cell	O
+line	O
+,	O
+which	O
+suggests	O
+that	O
+EBV	O
+and	O
+HIV	O
+-	O
+1	O
+infection	O
+of	O
+non	O
+-	O
+B	O
+cells	O
+may	O
+result	O
+in	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+activation	O
+.	O
+
+Mutation	O
+of	O
+the	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+the	O
+Rous	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+and	O
+gag	B-GENE
+enhancers	I-GENE
+.	O
+
+Nuclear	B-GENE
+protein	I-GENE
+phosphatase	I-GENE
+2A	I-GENE
+dephosphorylates	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+-	O
+phosphorylated	O
+CREB	B-GENE
+and	O
+regulates	O
+CREB	B-GENE
+transcriptional	O
+stimulation	O
+.	O
+
+We	O
+show	O
+that	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+activates	O
+JRE	B-GENE
+-	I-GENE
+IL6	I-GENE
+through	O
+an	O
+H7	O
+-	O
+sensitive	O
+pathway	O
+that	O
+does	O
+not	O
+involve	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+,	O
+cyclic	B-GENE
+AMP	I-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+,	O
+Ca	B-GENE
+(	I-GENE
+2	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+or	I-GENE
+calmodulin	I-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+,	O
+Ras	B-GENE
+,	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+or	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+)	O
+.	O
+
+Mutation	O
+of	O
+the	O
+presumptive	O
+phosphorylated	O
+tyrosine	O
+and	O
+threonine	O
+residues	O
+of	O
+Mpk1p	B-GENE
+individually	O
+to	O
+phenylalanine	O
+and	O
+alanine	O
+,	O
+respectively	O
+,	O
+severely	O
+impaired	O
+Mpk1p	B-GENE
+function	O
+.	O
+
+Growth	O
+factor	O
+stimulation	O
+rapidly	O
+induces	O
+a	O
+reversible	O
+change	O
+in	O
+the	O
+electrophoretic	O
+mobility	O
+of	O
+the	O
+ternary	O
+complex	O
+,	O
+accompanied	O
+by	O
+increased	O
+phosphorylation	O
+of	O
+the	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+C	I-GENE
+-	I-GENE
+terminal	I-GENE
+region	I-GENE
+and	O
+by	O
+the	O
+activation	O
+of	O
+a	O
+42	B-GENE
+kd	I-GENE
+cellular	I-GENE
+Elk	I-GENE
+-	I-GENE
+1	I-GENE
+kinase	I-GENE
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+situation	O
+in	O
+mammalian	O
+cells	O
+,	O
+prolonged	O
+exposure	O
+of	O
+the	O
+agonist	O
+(	O
+24	O
+h	O
+)	O
+does	O
+not	O
+result	O
+in	O
+down	O
+regulation	O
+of	O
+the	O
+remaining	O
+70	O
+%	O
+of	O
+the	O
+receptors	O
+.	O
+
+This	O
+stimulatory	O
+effect	O
+could	O
+also	O
+be	O
+elicited	O
+by	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+,	O
+which	O
+interacts	O
+with	O
+topo	B-GENE
+II	I-GENE
+,	O
+but	O
+not	O
+by	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+,	O
+which	O
+does	O
+not	O
+bind	O
+topo	B-GENE
+II	I-GENE
+in	O
+our	O
+in	O
+vitro	O
+assay	O
+.	O
+
+The	O
+regulation	O
+of	O
+Myf	B-GENE
+-	I-GENE
+5	I-GENE
+and	O
+MyoD	B-GENE
+function	O
+by	O
+a	O
+cAMP	O
+-	O
+dependent	O
+pathway	O
+may	O
+partly	O
+explain	O
+how	O
+external	O
+signals	O
+generated	O
+by	O
+serum	O
+and	O
+certain	O
+peptide	O
+growth	O
+factors	O
+can	O
+be	O
+transduced	O
+to	O
+the	O
+nucleus	O
+and	O
+inhibit	O
+dominant	O
+-	O
+acting	O
+factors	O
+that	O
+are	O
+responsible	O
+for	O
+myoblast	O
+differentiation	O
+.	O
+
+16	O
+,	O
+99	O
+-	O
+104	O
+)	O
+.	O
+
+We	O
+have	O
+previously	O
+reported	O
+that	O
+high	O
+level	O
+human	B-GENE
+desmin	I-GENE
+expression	O
+depends	O
+on	O
+a	O
+280	O
+-	O
+base	O
+pair	O
+muscle	O
+-	O
+specific	O
+enhancer	O
+which	O
+can	O
+function	O
+not	O
+only	O
+in	O
+myotubes	O
+,	O
+but	O
+can	O
+also	O
+activate	O
+gene	O
+expression	O
+in	O
+myoblasts	O
+.	O
+
+After	O
+surgery	O
+,	O
+patients	O
+self	O
+administered	O
+one	O
+of	O
+three	O
+possible	O
+postsurgical	O
+medications	O
+,	O
+which	O
+included	O
+placebo	O
+,	O
+codeine	O
+60	O
+mg	O
+,	O
+and	O
+ibuprofen	O
+400	O
+mg	O
+,	O
+when	O
+their	O
+pain	O
+reached	O
+a	O
+moderate	O
+or	O
+severe	O
+intensity	O
+.	O
+
+Replacement	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+5	O
+'	O
+-	O
+regulatory	O
+region	O
+with	O
+either	O
+of	O
+the	O
+mutants	O
+'	O
+cis	O
+-	O
+acting	O
+regulatory	O
+element	O
+resulted	O
+in	O
+the	O
+anaerobic	O
+expression	O
+of	O
+active	B-GENE
+Mn	I-GENE
+-	I-GENE
+superoxide	I-GENE
+dismutase	I-GENE
+.	O
+
+The	O
+orf61	B-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+when	O
+expressed	O
+from	O
+an	O
+exogenous	O
+promoter	O
+,	O
+inhibited	O
+int	B-GENE
+-	O
+mediated	O
+integration	O
+at	O
+the	O
+chromosomal	B-GENE
+attB	I-GENE
+site	I-GENE
+.	O
+
+Expression	O
+in	O
+established	O
+LCLs	O
+,	O
+occurring	O
+irrespective	O
+of	O
+virus	O
+producer	O
+status	O
+,	O
+was	O
+not	O
+a	O
+consequence	O
+of	O
+continued	O
+in	O
+vitro	O
+passage	O
+;	O
+thus	O
+,	O
+appropriately	O
+spliced	O
+BamHI	B-GENE
+-	I-GENE
+A	I-GENE
+transcripts	I-GENE
+could	O
+be	O
+amplified	O
+from	O
+normal	O
+B	O
+cells	O
+within	O
+1	O
+day	O
+of	O
+their	O
+experimental	O
+infection	O
+in	O
+vitro	O
+,	O
+along	O
+with	O
+BamHI	B-GENE
+-	I-GENE
+C	I-GENE
+/	I-GENE
+W	I-GENE
+promoter	O
+-	O
+initiated	O
+but	O
+not	O
+BamHI	B-GENE
+-	I-GENE
+F	I-GENE
+promoter	I-GENE
+-	I-GENE
+initiated	I-GENE
+mRNAs	I-GENE
+.	O
+
+Analysis	O
+by	O
+cell	O
+surface	O
+immunofluorescence	O
+showed	O
+that	O
+the	O
+UL28	B-GENE
+gene	I-GENE
+is	O
+not	O
+required	O
+for	O
+expression	O
+of	O
+viral	O
+glycoproteins	O
+on	O
+the	O
+surface	O
+of	O
+infected	O
+cells	O
+.	O
+
+Furthermore	O
+,	O
+a	O
+mutant	O
+receptor	O
+(	O
+Y977F	O
+/	O
+Y989F	O
+[	O
+PLC	B-GENE
+gamma	I-GENE
+-	O
+binding	O
+sites	O
+]	O
+)	O
+could	O
+fully	O
+activate	O
+Ras	B-GENE
+,	O
+and	O
+the	O
+direct	O
+activation	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+and	O
+calcium	O
+mobilization	O
+had	O
+almost	O
+no	O
+effect	O
+on	O
+the	O
+GDP	O
+/	O
+GTP	O
+state	O
+of	O
+Ras	B-GENE
+in	O
+this	O
+cell	O
+line	O
+.	O
+
+Estrogen	O
+treatment	O
+in	O
+high	O
+doses	O
+is	O
+effective	O
+in	O
+reducing	O
+adult	O
+stature	O
+in	O
+constitutionally	O
+tall	O
+girls	O
+.	O
+
+Uracil	B-GENE
+DNA	I-GENE
+glycosylase	I-GENE
+catalyzes	O
+the	O
+initial	O
+step	O
+in	O
+the	O
+repair	O
+pathway	O
+that	O
+removes	O
+potentially	O
+mutagenic	O
+uracil	O
+from	O
+duplex	O
+DNA	O
+.	O
+
+Current	O
+clinical	O
+trials	O
+should	O
+answer	O
+the	O
+question	O
+of	O
+which	O
+of	O
+the	O
+therapeutic	O
+options	O
+impairs	O
+quality	O
+of	O
+life	O
+less	O
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+focus	O
+on	O
+the	O
+genetics	O
+of	O
+the	O
+region	O
+of	O
+the	O
+17	B-GENE
+hep	I-GENE
+syn	I-GENE
+gB	I-GENE
+gene	I-GENE
+that	O
+conferred	O
+both	O
+the	O
+syncytial	O
+and	O
+pathogenic	O
+phenotypes	O
+to	O
+17	B-GENE
+syn	I-GENE
++	I-GENE
+.	O
+
+Recipients	O
+with	O
+acute	O
+leukaemia	O
+in	O
+first	O
+remission	O
+or	O
+chronic	O
+myeloid	O
+leukaemia	O
+in	O
+first	O
+chronic	O
+phase	O
+were	O
+analysed	O
+as	O
+good	O
+risk	O
+,	O
+and	O
+those	O
+beyond	O
+these	O
+stages	O
+,	O
+as	O
+poor	O
+risk	O
+patients	O
+.	O
+
+Elledge	O
+,	O
+P	O
+.	O
+
+Drugs	O
+suppressed	O
+>	O
+or	O
+=	O
+75	O
+%	O
+of	O
+the	O
+total	O
+premature	O
+ventricular	O
+contractions	O
+in	O
+all	O
+patients	O
+who	O
+had	O
+both	O
+use	O
+-	O
+dependent	O
+QRS	O
+prolongation	O
+and	O
+reverse	O
+use	O
+-	O
+dependent	O
+QT	O
+prolongation	O
+,	O
+in	O
+79	O
+%	O
+of	O
+patients	O
+with	O
+use	O
+-	O
+dependent	O
+QRS	O
+prolongation	O
+alone	O
+,	O
+in	O
+70	O
+%	O
+with	O
+reverse	O
+use	O
+-	O
+dependent	O
+QT	O
+prolongation	O
+alone	O
+,	O
+and	O
+in	O
+11	O
+%	O
+with	O
+neither	O
+use	O
+-	O
+dependent	O
+QRS	O
+prolongation	O
+nor	O
+reverse	O
+use	O
+-	O
+dependent	O
+QT	O
+prolongation	O
+.	O
+
+Losses	O
+during	O
+the	O
+complete	O
+procedure	O
+are	O
+corrected	O
+for	O
+using	O
+radioactive	O
+estrogen	O
+conjugates	O
+during	O
+the	O
+first	O
+steps	O
+and	O
+later	O
+by	O
+adding	O
+deuterated	O
+internal	O
+standards	O
+of	O
+all	O
+compounds	O
+measured	O
+(	O
+matairesinol	O
+,	O
+enterodiol	O
+,	O
+enterolactone	O
+,	O
+daidzein	O
+,	O
+O	O
+-	O
+desmethylangolensin	O
+,	O
+equol	O
+,	O
+and	O
+genistein	O
+)	O
+.	O
+
+The	O
+Sp1	B-GENE
+region	I-GENE
+,	O
+however	O
+,	O
+is	O
+converted	O
+to	O
+a	O
+functionally	O
+strong	O
+TRE	O
+by	O
+the	O
+viral	B-GENE
+tat	I-GENE
+factor	I-GENE
+.	O
+
+Three	O
+group	O
+1	O
+patients	O
+developed	O
+CMV	O
+disease	O
+;	O
+1	O
+group	O
+2	O
+patient	O
+developed	O
+CMV	O
+hepatitis	O
+.	O
+
+The	O
+ability	O
+of	O
+spt2	B-GENE
+mutations	I-GENE
+to	O
+suppress	O
+the	O
+transcriptional	O
+interference	O
+caused	O
+by	O
+the	O
+delta	B-GENE
+promoter	I-GENE
+insertion	I-GENE
+his	I-GENE
+-	I-GENE
+4	I-GENE
+-	I-GENE
+912	I-GENE
+delta	I-GENE
+correlates	O
+with	O
+an	O
+increase	O
+in	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+HIS4	I-GENE
+mRNA	I-GENE
+levels	O
+.	O
+
+Nuclear	O
+localization	O
+and	O
+protein	O
+sequence	O
+similarities	O
+suggested	O
+that	O
+the	O
+SPT2	B-GENE
+/	O
+SIN1	B-GENE
+protein	O
+may	O
+be	O
+related	O
+to	O
+the	O
+nonhistone	B-GENE
+chromosomal	I-GENE
+protein	I-GENE
+HMG1	I-GENE
+.	O
+
+The	O
+conserved	O
+ninth	O
+C	O
+-	O
+terminal	O
+heptad	O
+in	O
+thyroid	O
+hormone	O
+and	O
+retinoic	B-GENE
+acid	I-GENE
+receptors	I-GENE
+mediates	O
+diverse	O
+responses	O
+by	O
+affecting	O
+heterodimer	O
+but	O
+not	O
+homodimer	O
+formation	O
+.	O
+
+Genetic	O
+interactions	O
+between	O
+BCK2	B-GENE
+and	O
+other	O
+pathway	O
+components	O
+suggested	O
+that	O
+BCK2	B-GENE
+functions	O
+on	O
+a	O
+common	O
+pathway	O
+branch	O
+with	O
+PPZ1	B-GENE
+and	O
+PPZ2	B-GENE
+.	O
+
+Steroidogenic	B-GENE
+factor	I-GENE
+1	I-GENE
+,	O
+an	O
+orphan	B-GENE
+nuclear	I-GENE
+receptor	I-GENE
+,	O
+regulates	O
+the	O
+expression	O
+of	O
+the	O
+rat	B-GENE
+aromatase	I-GENE
+gene	I-GENE
+in	O
+gonadal	O
+tissues	O
+.	O
+
+To	O
+study	O
+the	O
+functional	O
+differences	O
+between	O
+cutaneous	O
+HPV5	O
+and	O
+HPV8	O
+E7s	B-GENE
+and	O
+genital	B-GENE
+HPV16	I-GENE
+E7	I-GENE
+,	O
+we	O
+cloned	O
+each	O
+of	O
+the	O
+E7	B-GENE
+open	O
+reading	O
+frames	O
+and	O
+tested	O
+their	O
+immortalizing	O
+and	O
+transforming	O
+activities	O
+,	O
+the	O
+binding	O
+ability	O
+of	O
+their	O
+products	O
+with	O
+retinoblastoma	B-GENE
+protein	I-GENE
+(	O
+RB	B-GENE
+)	O
+and	O
+their	O
+complementation	O
+activity	O
+of	O
+a	O
+RB	B-GENE
+-	I-GENE
+nonbinding	I-GENE
+adenovirus	I-GENE
+E1A	I-GENE
+mutant	I-GENE
+.	O
+
+The	O
+rhaB	B-GENE
+transcription	I-GENE
+start	I-GENE
+site	I-GENE
+was	O
+mapped	O
+to	O
+-	O
+24	O
+relative	O
+to	O
+the	O
+start	O
+of	O
+translation	O
+.	O
+
+Several	O
+lines	O
+of	O
+evidence	O
+demonstrate	O
+that	O
+this	O
+growth	O
+inhibition	O
+requires	O
+active	O
+PKA	B-GENE
+subunits	I-GENE
+and	O
+cAMP	O
+:	O
+(	O
+i	O
+)	O
+this	O
+phenotype	O
+is	O
+dependent	O
+on	O
+cAMP	O
+since	O
+it	O
+is	O
+not	O
+seen	O
+in	O
+a	O
+strain	O
+lacking	O
+adenylyl	B-GENE
+cyclase	I-GENE
+activity	O
+,	O
+but	O
+the	O
+growth	O
+rate	O
+of	O
+these	O
+transformants	O
+is	O
+slower	O
+when	O
+exogenous	O
+cAMP	O
+is	O
+added	O
+;	O
+(	O
+ii	O
+)	O
+normal	O
+growth	O
+occurs	O
+when	O
+wild	O
+-	O
+type	O
+RI	B-GENE
+cDNA	O
+is	O
+replaced	O
+by	O
+a	O
+mutant	B-GENE
+RI	I-GENE
+cDNA	I-GENE
+encoding	O
+a	O
+RI	B-GENE
+protein	I-GENE
+with	O
+reduced	O
+cAMP	O
+binding	O
+;	O
+and	O
+(	O
+iii	O
+)	O
+the	O
+growth	O
+-	O
+inhibited	O
+phenotype	O
+of	O
+the	O
+transformed	O
+BL21	O
+(	O
+DE3	O
+)	O
+cells	O
+requires	O
+soluble	O
+,	O
+active	O
+C	B-GENE
+alpha	I-GENE
+protein	I-GENE
+.	O
+
+Liu	O
+,	O
+B	O
+.	O
+
+BCR	B-GENE
+-	O
+ABL	B-GENE
+and	O
+v	B-GENE
+-	I-GENE
+abl	I-GENE
+oncogenes	I-GENE
+induce	O
+distinct	O
+patterns	O
+of	O
+thymic	O
+lymphoma	O
+involving	O
+different	O
+lymphocyte	O
+subsets	O
+.	O
+
+These	O
+experiments	O
+confirm	O
+that	O
+the	O
+6	O
+-	O
+S	O
+liganded	O
+form	O
+of	O
+the	O
+receptor	O
+identified	O
+in	O
+nuclear	O
+extracts	O
+of	O
+cells	O
+treated	O
+with	O
+2	O
+,	O
+3	O
+,	O
+7	O
+,	O
+8	O
+-	O
+tetrachlorodibenzo	O
+-	O
+p	O
+-	O
+dioxin	O
+(	O
+TCDD	O
+)	O
+contains	O
+the	O
+Ah	B-GENE
+receptor	I-GENE
+protein	I-GENE
+and	O
+ARNT	B-GENE
+but	O
+not	O
+the	O
+90	B-GENE
+-	I-GENE
+kDa	I-GENE
+heat	I-GENE
+shock	I-GENE
+protein	I-GENE
+.	O
+
+LDL	B-GENE
+cholesterol	I-GENE
+decreased	O
+from	O
+4	O
+.	O
+74	O
++	O
+/	O
+-	O
+0	O
+.	O
+87	O
+to	O
+3	O
+.	O
+78	O
++	O
+/	O
+-	O
+0	O
+.	O
+78	O
+mmol	O
+/	O
+l	O
+after	O
+8	O
+weeks	O
+on	O
+simvastatin	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+and	O
+apo	B-GENE
+B	I-GENE
+fell	O
+from	O
+142	O
++	O
+/	O
+-	O
+31	O
+to	O
+112	O
++	O
+/	O
+-	O
+22	O
+mg	O
+/	O
+dl	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+LDL	B-GENE
+cholesterol	I-GENE
+decreased	O
+from	O
+4	O
+.	O
+74	O
++	O
+/	O
+-	O
+0	O
+.	O
+87	O
+to	O
+3	O
+.	O
+78	O
++	O
+/	O
+-	O
+0	O
+.	O
+78	O
+mmol	O
+/	O
+l	O
+after	O
+8	O
+weeks	O
+on	O
+simvastatin	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+and	O
+apo	B-GENE
+B	I-GENE
+fell	O
+from	O
+142	O
++	O
+/	O
+-	O
+31	O
+to	O
+112	O
++	O
+/	O
+-	O
+22	O
+mg	O
+/	O
+dl	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+This	O
+negative	O
+element	O
+may	O
+,	O
+at	O
+least	O
+in	O
+part	O
+,	O
+be	O
+responsible	O
+for	O
+the	O
+cell	O
+type	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+DGK	B-GENE
+gene	I-GENE
+.	O
+
+Regulated	O
+activity	O
+of	O
+the	O
+distal	O
+promoter	O
+-	O
+like	O
+element	O
+of	O
+the	O
+human	B-GENE
+corticotropin	I-GENE
+-	I-GENE
+releasing	I-GENE
+hormone	I-GENE
+gene	I-GENE
+and	O
+secondary	O
+structural	O
+features	O
+of	O
+its	O
+corresponding	O
+transcripts	O
+.	O
+
+A	O
+new	O
+bioencapsulation	O
+technology	O
+for	O
+microbial	O
+inoculants	O
+.	O
+
+We	O
+linked	O
+hypersensitivity	O
+site	O
+2	O
+(	O
+HS2	O
+)	O
+from	O
+the	O
+locus	O
+control	O
+region	O
+(	O
+LCR	O
+)	O
+to	O
+a	O
+A	B-GENE
+gamma	I-GENE
+-	I-GENE
+globin	I-GENE
+gene	O
+(	O
+A	B-GENE
+gamma	I-GENE
+*	I-GENE
+)	O
+mutationally	O
+marked	O
+to	O
+allow	O
+its	O
+transcript	O
+to	O
+be	O
+distinguished	O
+from	O
+endogenous	O
+gamma	B-GENE
+-	I-GENE
+globin	I-GENE
+mRNA	O
+.	O
+
+INTERVENTIONS	O
+-	O
+-	O
+Patients	O
+allocated	O
+to	O
+treatment	O
+with	O
+levodopa	B-GENE
+/	I-GENE
+dopa	I-GENE
+decarboxylase	I-GENE
+inhibitor	O
+alone	O
+(	O
+arm	O
+1	O
+)	O
+,	O
+levodopa	B-GENE
+/	I-GENE
+decarboxylase	I-GENE
+inhibitor	O
+/	O
+selegiline	O
+in	O
+combination	O
+(	O
+arm	O
+2	O
+)	O
+,	O
+or	O
+bromocriptine	O
+(	O
+arm	O
+3	O
+)	O
+.	O
+
+It	O
+contains	O
+three	O
+putative	O
+binding	O
+sites	O
+for	O
+transcription	B-GENE
+factor	I-GENE
+Sp1	I-GENE
+as	O
+well	O
+as	O
+several	O
+short	O
+sequences	O
+that	O
+are	O
+similar	O
+to	O
+known	O
+cis	O
+-	O
+acting	O
+enhancers	O
+or	O
+binding	O
+sites	O
+for	O
+transcription	O
+factors	O
+.	O
+
+French	O
+bean	O
+contains	O
+a	O
+small	O
+family	O
+of	O
+genes	B-GENE
+encoding	I-GENE
+PAL	I-GENE
+and	O
+two	O
+of	O
+these	O
+genes	O
+,	O
+PAL2	B-GENE
+and	O
+PAL3	B-GENE
+,	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+differentially	O
+expressed	O
+at	O
+the	O
+mRNA	O
+level	O
+in	O
+bean	O
+tissues	O
+.	O
+
+Plasma	O
+thromboxane	O
+B2	O
+levels	O
+in	O
+the	O
+older	O
+group	O
+were	O
+about	O
+double	O
+those	O
+in	O
+younger	O
+piglets	O
+.	O
+
+By	O
+stepwise	O
+linear	O
+multiple	O
+regression	O
+analysis	O
+,	O
+ionized	O
+magnesium	O
+was	O
+significantly	O
+related	O
+to	O
+cyclosporin	O
+trough	O
+level	O
+and	O
+total	O
+cholesterol	O
+but	O
+not	O
+to	O
+serum	O
+creatinine	O
+,	O
+time	O
+after	O
+transplant	O
+or	O
+the	O
+dose	O
+of	O
+cyclosporin	O
+.	O
+
+The	O
+human	B-GENE
+insulin	I-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+II	I-GENE
+(	O
+IGF	B-GENE
+-	I-GENE
+II	I-GENE
+)	O
+gene	O
+contains	O
+four	O
+promoters	O
+(	O
+P1	O
+,	O
+P2	O
+,	O
+P3	O
+and	O
+P4	O
+)	O
+.	O
+
+Moreover	O
+,	O
+in	O
+transient	O
+transfection	O
+assays	O
+,	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+alone	O
+activated	O
+reporter	O
+constructs	O
+containing	O
+the	O
+JB	O
+cis	O
+-	O
+element	O
+,	O
+and	O
+the	O
+activation	O
+was	O
+shown	O
+to	O
+be	O
+dependent	O
+on	O
+a	O
+glutamine	O
+-	O
+rich	O
+sequence	O
+in	O
+the	O
+amino	O
+-	O
+terminal	O
+portion	O
+of	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+.	O
+
+Army	O
+veterans	O
+given	O
+yellow	O
+fever	O
+vaccine	O
+contaminated	O
+with	O
+hepatitis	O
+B	O
+virus	O
+in	O
+1942	O
+and	O
+controls	O
+and	O
+(	O
+b	O
+)	O
+a	O
+case	O
+-	O
+control	O
+study	O
+comparing	O
+veterans	O
+with	O
+hepatocellular	O
+carcinoma	O
+in	O
+Veterans	O
+Affairs	O
+hospitals	O
+with	O
+matched	O
+controls	O
+with	O
+respect	O
+to	O
+receipt	O
+of	O
+contaminated	O
+vaccine	O
+in	O
+1942	O
+.	O
+
+They	O
+were	O
+found	O
+to	O
+be	O
+seropositive	O
+for	O
+antibodies	O
+to	O
+hepatitis	O
+C	O
+virus	O
+by	O
+second	O
+-	O
+generation	O
+testing	O
+(	O
+RIBA	O
+2	O
+,	O
+Ortho	O
+Diagnostic	O
+Systems	O
+Inc	O
+,	O
+Westwood	O
+,	O
+MA	O
+)	O
+.	O
+
+When	O
+introduced	O
+into	O
+recJ	B-GENE
++	I-GENE
+strains	O
+,	O
+srjA	B-GENE
+mutations	O
+conferred	O
+hyperrecombinational	O
+and	O
+hyper	B-GENE
+-	I-GENE
+UVr	I-GENE
+phenotypes	O
+.	O
+
+Distinguishing	O
+roles	O
+of	O
+the	O
+membrane	O
+-	O
+cytoskeleton	O
+and	O
+cadherin	B-GENE
+mediated	O
+cell	O
+-	O
+cell	O
+adhesion	O
+in	O
+generating	O
+different	O
+Na	B-GENE
++	I-GENE
+,	I-GENE
+K	I-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+-	I-GENE
+ATPase	I-GENE
+distributions	O
+in	O
+polarized	O
+epithelia	O
+.	O
+
+Neonatal	O
+lupus	O
+erythematosus	O
+is	O
+most	O
+often	O
+associated	O
+with	O
+autoantibodies	O
+against	O
+Ro	B-GENE
+and	O
+La	B-GENE
+antigens	O
+.	O
+
+Genetic	O
+abnormalities	O
+that	O
+could	O
+lead	O
+to	O
+mutagenesis	O
+include	O
+chromosomal	O
+abnormalities	O
+and	O
+single	O
+-	O
+gene	O
+mutations	O
+.	O
+
+Hops	O
+,	O
+and	O
+L	O
+.	O
+
+Continued	O
+absorption	O
+of	O
+amino	O
+acids	O
+by	O
+the	O
+NBB	O
+carrier	O
+(	O
+for	O
+neutral	O
+amino	O
+acids	O
+)	O
+,	O
+the	O
+Y	O
++	O
+system	O
+(	O
+for	O
+dibasic	O
+amino	O
+acids	O
+)	O
+,	O
+and	O
+the	O
+PHE	O
+carrier	O
+were	O
+operative	O
+even	O
+during	O
+the	O
+actively	O
+purging	O
+stage	O
+of	O
+watery	O
+diarrhoea	O
+due	O
+to	O
+cholera	O
+.	O
+
+1	O
+)	O
+CFDN	O
+,	O
+AMPC	O
+and	O
+MNZ	O
+showed	O
+a	O
+potent	O
+antimicrobial	O
+activity	O
+against	O
+H	O
+.	O
+pylori	O
+,	O
+and	O
+especially	O
+,	O
+AMPC	O
+showed	O
+a	O
+marked	O
+bactericidal	O
+activity	O
+in	O
+a	O
+short	O
+time	O
+.	O
+
+Creutzfeldt	O
+-	O
+Jakob	O
+disease	O
+and	O
+lyophilised	O
+dura	O
+mater	O
+grafts	O
+:	O
+report	O
+of	O
+two	O
+cases	O
+.	O
+
+A	O
+high	O
+mean	O
+intensity	O
+of	O
+CLTPA	O
+(	O
+standardized	O
+multivariate	O
+regression	O
+coefficient	O
+beta	O
+-	O
+0	O
+.	O
+059	O
+,	O
+p	O
+=	O
+0	O
+.	O
+020	O
+)	O
+and	O
+a	O
+high	O
+maximal	O
+oxygen	O
+uptake	O
+(	O
+beta	O
+-	O
+0	O
+.	O
+163	O
+,	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+were	O
+associated	O
+with	O
+reduced	O
+plasma	B-GENE
+fibrinogen	I-GENE
+when	O
+adjusting	O
+for	O
+the	O
+strongest	O
+covariates	O
+.	O
+
+What	O
+young	O
+people	O
+think	O
+and	O
+do	O
+when	O
+the	O
+option	O
+for	O
+cystic	O
+fibrosis	O
+carrier	O
+testing	O
+is	O
+available	O
+.	O
+
+A	O
+patient	O
+matches	O
+a	O
+PIC	O
+patient	O
+if	O
+both	O
+have	O
+the	O
+same	O
+mechanism	O
+of	O
+injury	O
+,	O
+the	O
+same	O
+coding	O
+of	O
+Revised	O
+Trauma	O
+Score	O
+variables	O
+(	O
+Glascow	O
+Coma	O
+Scale	O
+score	O
+,	O
+systolic	O
+blood	O
+pressure	O
+,	O
+respiratory	O
+rate	O
+)	O
+,	O
+the	O
+same	O
+coded	O
+age	O
+per	O
+A	O
+Severity	O
+Characterization	O
+of	O
+Trauma	O
+)	O
+(	O
+ASCOT	O
+)	O
+,	O
+and	O
+if	O
+they	O
+differ	O
+by	O
+no	O
+more	O
+than	O
+0	O
+.	O
+5	O
+for	O
+A	O
+,	O
+B	O
+,	O
+and	O
+C	O
+(	O
+the	O
+ASCOT	O
+components	O
+for	O
+serious	O
+injuries	O
+)	O
+.	O
+
+Skin	O
+and	O
+bowel	O
+TPO2	O
+varied	O
+with	O
+DO2	O
+and	O
+each	O
+other	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+cosmid	O
+containing	O
+DNA	O
+that	O
+corresponds	O
+to	O
+the	O
+site	O
+of	O
+transposon	O
+insertion	O
+in	O
+257DH4	O
+and	O
+have	O
+localized	O
+Tn5	B-GENE
+on	O
+an	O
+8	B-GENE
+.	I-GENE
+0	I-GENE
+kb	I-GENE
+EcoRI	I-GENE
+fragment	I-GENE
+.	O
+
+The	O
+scr	B-GENE
+regulon	I-GENE
+of	O
+pUR400	O
+and	O
+the	O
+chromosomally	B-GENE
+encoded	I-GENE
+scr	I-GENE
+regulon	I-GENE
+of	I-GENE
+Klebsiella	I-GENE
+pneumoniae	I-GENE
+KAY2026	I-GENE
+are	O
+both	O
+negatively	O
+controlled	O
+by	O
+a	O
+specific	O
+repressor	O
+(	O
+ScrR	B-GENE
+)	O
+.	O
+
+Although	O
+the	O
+molecular	O
+mechanisms	O
+involved	O
+in	O
+this	O
+regulation	O
+are	O
+currently	O
+being	O
+elucidated	O
+,	O
+very	O
+little	O
+is	O
+known	O
+about	O
+the	O
+trans	O
+-	O
+acting	O
+factors	O
+that	O
+allow	O
+expression	O
+of	O
+the	O
+nitrate	B-GENE
+and	I-GENE
+nitrite	I-GENE
+reductase	I-GENE
+genes	I-GENE
+which	O
+code	O
+for	O
+the	O
+first	O
+enzymes	O
+in	O
+the	O
+pathway	O
+.	O
+
+The	O
+Ntl1	B-GENE
+gene	I-GENE
+is	O
+present	O
+as	O
+a	O
+unique	O
+copy	O
+in	O
+the	O
+diploid	O
+N	O
+.	O
+plumbaginifolia	O
+species	O
+.	O
+
+Transient	O
+transfection	O
+experiments	O
+revealed	O
+that	O
+Pax	B-GENE
+-	I-GENE
+8	I-GENE
+isoforms	I-GENE
+a	I-GENE
+and	I-GENE
+b	I-GENE
+,	O
+but	O
+not	O
+c	O
+and	O
+d	O
+,	O
+strongly	O
+stimulate	O
+transcription	O
+from	O
+a	O
+promoter	O
+containing	O
+six	O
+copies	O
+of	O
+a	O
+paired	B-GENE
+-	I-GENE
+domain	I-GENE
+recognition	I-GENE
+sequence	I-GENE
+.	O
+
+The	O
+amino	O
+-	O
+terminal	O
+third	O
+of	O
+the	O
+protein	O
+contains	O
+a	O
+high	B-GENE
+-	I-GENE
+mobility	I-GENE
+-	I-GENE
+group	I-GENE
+motif	I-GENE
+characteristic	O
+of	O
+DNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+We	O
+have	O
+examined	O
+the	O
+ability	O
+of	O
+various	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+subunits	I-GENE
+to	O
+bind	O
+to	O
+,	O
+and	O
+activate	O
+transcription	O
+from	O
+,	O
+the	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+promoter	I-GENE
+.	O
+
+When	O
+multiple	O
+copies	O
+of	O
+the	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+site	I-GENE
+were	O
+linked	O
+to	O
+an	O
+enhancerless	O
+simian	B-GENE
+virus	I-GENE
+40	I-GENE
+promoter	I-GENE
+,	O
+this	O
+element	O
+was	O
+able	O
+to	O
+mediate	O
+phorbol	O
+ester	O
+-	O
+or	O
+lipopolysaccharide	O
+-	O
+inducible	O
+gene	O
+expression	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+3	O
+'	O
+-	O
+end	O
+-	O
+adjacent	O
+sequence	O
+CA	O
+(	O
+N	O
+)	O
+3	O
+-	O
+10AGTNNAA	O
+,	O
+conserved	O
+in	O
+plant	O
+Pol	B-GENE
+II	I-GENE
+-	O
+specific	O
+U	B-GENE
+snRNA	I-GENE
+genes	I-GENE
+,	O
+is	O
+essential	O
+for	O
+the	O
+3	O
+'	O
+-	O
+end	O
+formation	O
+of	O
+U2	B-GENE
+transcripts	I-GENE
+and	O
+,	O
+similar	O
+to	O
+the	O
+vertebrate	O
+3	O
+'	O
+box	O
+,	O
+is	O
+highly	O
+tolerant	O
+to	O
+mutation	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+Rb	B-GENE
+protein	I-GENE
+is	O
+interacting	O
+with	O
+some	O
+component	O
+(	O
+s	O
+)	O
+of	O
+the	O
+cell	O
+cycle	O
+-	O
+regulatory	O
+machinery	O
+during	O
+G2	O
+phase	O
+.	O
+
+MDBP	B-GENE
+from	O
+HeLa	O
+and	O
+Raji	O
+cells	O
+formed	O
+DNA	O
+-	O
+protein	O
+complexes	O
+with	O
+X	O
+-	O
+box	O
+oligonucleotides	O
+that	O
+coelectrophoresed	O
+with	O
+those	O
+containing	O
+standard	O
+MDBP	B-GENE
+sites	I-GENE
+.	O
+
+Transgenic	O
+mice	O
+harboring	O
+the	O
+rat	O
+TnI	B-GENE
+-	O
+CAT	B-GENE
+fusion	O
+gene	O
+expressed	O
+the	O
+reporter	O
+specifically	O
+in	O
+the	O
+skeletal	O
+muscle	O
+.	O
+
+The	O
+ADP	B-GENE
+-	I-GENE
+ribosylation	I-GENE
+factor	I-GENE
+(	O
+ARF	B-GENE
+)	O
+family	O
+is	O
+one	O
+of	O
+four	O
+subfamilies	O
+of	O
+the	O
+RAS	B-GENE
+superfamily	I-GENE
+of	O
+low	B-GENE
+molecular	I-GENE
+weight	I-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+(	O
+G	B-GENE
+proteins	I-GENE
+)	O
+.	O
+
+The	O
+E1	B-GENE
+gene	I-GENE
+is	O
+located	O
+within	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+gene	O
+for	O
+RCC1	B-GENE
+,	O
+a	O
+protein	O
+that	O
+regulates	O
+onset	O
+of	O
+mitosis	O
+.	O
+
+Genomic	O
+Southern	O
+blot	O
+analysis	O
+and	O
+chromosome	O
+mapping	O
+showed	O
+that	O
+GPRK6	B-GENE
+hybridizes	O
+to	O
+two	O
+closely	O
+related	O
+genes	O
+located	O
+on	O
+chromosomes	O
+5	O
+and	O
+13	O
+and	O
+are	O
+,	O
+therefore	O
+,	O
+distinct	O
+from	O
+the	O
+GPRK	B-GENE
+located	O
+near	O
+the	O
+Huntington	B-GENE
+disease	I-GENE
+locus	I-GENE
+on	O
+chromosome	O
+4	O
+.	O
+
+Metabolic	O
+labeling	O
+studies	O
+in	O
+S	O
+.	O
+cerevisiae	O
+and	O
+co	O
+-	O
+expression	O
+of	O
+nmt72p	B-GENE
+with	O
+several	O
+protein	O
+substrates	O
+of	O
+Nmt1p	B-GENE
+in	O
+Escherichia	O
+coli	O
+indicate	O
+that	O
+the	O
+Leu99	O
+-	O
+-	O
+>	O
+Pro	O
+substitution	O
+causes	O
+a	O
+reduction	O
+in	O
+the	O
+acylation	O
+of	O
+some	O
+but	O
+not	O
+all	O
+protein	O
+substrates	O
+.	O
+
+These	O
+CTD	B-GENE
+kinases	I-GENE
+,	O
+designated	O
+CTDK1	B-GENE
+and	O
+CTDK2	B-GENE
+,	O
+are	O
+fractionated	O
+by	O
+chromatography	O
+on	O
+Mono	O
+Q	O
+.	O
+
+Previously	O
+,	O
+we	O
+identified	O
+a	O
+51	O
+-	O
+bp	O
+promoter	O
+fragment	O
+,	O
+oligo31	O
+/	O
+32	O
+,	O
+which	O
+conferred	O
+heat	O
+shock	O
+inducibility	O
+on	O
+the	O
+heterologous	O
+CYC1	B-GENE
+-	O
+lacZ	B-GENE
+reporter	O
+gene	O
+in	O
+S	O
+.	O
+cerevisiae	O
+(	O
+N	O
+.	O
+
+To	O
+identify	O
+factors	O
+that	O
+may	O
+modify	O
+the	O
+heterosexual	O
+transmission	O
+of	O
+human	O
+T	O
+cell	O
+leukemia	O
+/	O
+lymphoma	O
+virus	O
+type	O
+I	O
+(	O
+HTLV	O
+-	O
+I	O
+)	O
+,	O
+534	O
+married	O
+couples	O
+enrolled	O
+in	O
+the	O
+Miyazaki	O
+Cohort	O
+Study	O
+between	O
+November	O
+1984	O
+and	O
+April	O
+1989	O
+were	O
+studied	O
+:	O
+95	O
+husband	O
+HTLV	O
+-	O
+I	O
+-	O
+seropositive	O
+(	O
+H	O
++	O
+)	O
+/	O
+wife	O
+seropositive	O
+(	O
+W	O
++	O
+)	O
+,	O
+33	O
+H	O
++	O
+/	O
+W	O
+-	O
+,	O
+64	O
+H	O
+-	O
+/	O
+W	O
++	O
+,	O
+and	O
+342	O
+H	O
+-	O
+/	O
+W	O
+-	O
+.	O
+
+To	O
+characterize	O
+the	O
+expression	O
+of	O
+this	O
+DNA	B-GENE
+repair	I-GENE
+enzyme	I-GENE
+,	O
+we	O
+have	O
+isolated	O
+the	O
+corresponding	O
+genomic	O
+clone	O
+.	O
+
+L	O
+.	O
+,	O
+Stange	O
+,	O
+G	O
+.	O
+,	O
+Markovich	O
+,	O
+D	O
+.	O
+,	O
+Biber	O
+,	O
+J	O
+.	O
+,	O
+Testar	O
+,	O
+X	O
+.	O
+,	O
+Zorzano	O
+,	O
+A	O
+.	O
+,	O
+Palacin	O
+,	O
+M	O
+.	O
+,	O
+and	O
+Murer	O
+,	O
+H	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+gene	O
+predicts	O
+a	O
+polypeptide	O
+of	O
+215	O
+amino	O
+acids	O
+(	O
+25	O
+.	O
+2	O
+kDa	O
+)	O
+with	O
+two	O
+putative	O
+membrane	O
+-	O
+spanning	O
+domains	O
+.	O
+
+SAECG	O
+,	O
+echocardiography	O
+and	O
+thallium	O
+-	O
+201	O
+imaging	O
+were	O
+performed	O
+before	O
+and	O
+1	O
+month	O
+after	O
+attempted	O
+angioplasty	O
+.	O
+
+They	O
+were	O
+called	O
+PACE4	B-GENE
+and	O
+PC4	B-GENE
+.	O
+
+Both	O
+fusion	O
+proteins	O
+form	O
+stable	O
+specific	O
+complexes	O
+with	O
+a	O
+short	O
+DNA	O
+duplex	O
+harboring	O
+the	O
+CTGT	O
+(	O
+at	O
+)	O
+4ACAG	O
+consensus	O
+sequence	O
+of	O
+the	O
+LexA	B-GENE
+repressor	I-GENE
+.	O
+
+Ten	O
+selenocysteine	O
+residues	O
+(	O
+deduced	O
+)	O
+are	O
+present	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Free	O
+protein	B-GENE
+S	I-GENE
+deficiency	O
+is	O
+common	O
+among	O
+hospitalized	O
+patients	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+a	O
+recognized	O
+predisposing	O
+condition	O
+.	O
+
+During	O
+the	O
+past	O
+decade	O
+,	O
+different	O
+types	O
+of	O
+endogenous	O
+retroviral	O
+sequences	O
+have	O
+been	O
+defined	O
+in	O
+the	O
+human	O
+genome	O
+usually	O
+by	O
+low	O
+stringency	O
+hybridization	O
+employing	O
+DNA	O
+probes	O
+of	O
+evolutionary	O
+conserved	O
+animal	O
+retrovirus	O
+genes	O
+.	O
+
+As	O
+the	O
+components	O
+of	O
+these	O
+complexes	O
+,	O
+at	O
+least	O
+five	O
+TRBPs	B-GENE
+(	O
+p30	B-GENE
+,	O
+p37	B-GENE
+,	O
+p46	B-GENE
+,	O
+p50	B-GENE
+,	O
+and	O
+p56	B-GENE
+)	O
+showing	O
+specific	O
+binding	O
+to	O
+the	O
+TAR	O
+RNA	O
+were	O
+detected	O
+in	O
+the	O
+uv	O
+cross	O
+-	O
+linking	O
+assay	O
+.	O
+
+The	O
+obvious	O
+functional	O
+necessity	O
+for	O
+editing	O
+in	O
+kinetoplastid	O
+mitochondria	O
+is	O
+the	O
+formation	O
+of	O
+translatable	O
+mRNAs	O
+.	O
+
+An	O
+extensive	O
+inverted	O
+repeat	O
+is	O
+present	O
+3	O
+'	O
+of	O
+rpeA	B-GENE
+;	O
+inverted	O
+repeats	O
+are	O
+found	O
+downstream	O
+of	O
+all	O
+PE	B-GENE
+operons	I-GENE
+sequenced	O
+to	O
+date	O
+,	O
+although	O
+the	O
+sequence	O
+is	O
+not	O
+conserved	O
+.	O
+
+Large	O
+differences	O
+between	O
+the	O
+groups	O
+were	O
+not	O
+observed	O
+in	O
+HA	B-GENE
+-	I-GENE
+synthesizing	I-GENE
+enzyme	I-GENE
+activity	O
+,	O
+but	O
+degradative	O
+enzyme	O
+activity	O
+was	O
+much	O
+higher	O
+in	O
+aspirin	O
+-	O
+induced	O
+asthma	O
+-	O
+related	O
+polyps	O
+than	O
+in	O
+other	O
+types	O
+of	O
+nasal	O
+polyps	O
+tested	O
+.	O
+
+In	O
+the	O
+multivariate	O
+analysis	O
+,	O
+six	O
+variables	O
+were	O
+independently	O
+correlated	O
+with	O
+survival	O
+:	O
+blood	O
+urea	O
+nitrogen	O
+level	O
+,	O
+serum	B-GENE
+aspartate	I-GENE
+aminotransferase	I-GENE
+level	O
+,	O
+community	O
+-	O
+acquired	O
+vs	O
+.	O
+hospital	O
+-	O
+acquired	O
+peritonitis	O
+,	O
+age	O
+,	O
+Child	O
+-	O
+Pugh	O
+score	O
+and	O
+ileus	O
+.	O
+
+Localization	O
+of	O
+the	O
+intronless	O
+gene	O
+coding	O
+for	O
+calmodulin	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+CLP	B-GENE
+to	O
+human	O
+chromosome	O
+10p13	O
+-	O
+ter	O
+.	O
+
+In	O
+wandering	O
+stage	O
+larvae	O
+,	O
+the	O
+OBP	B-GENE
+transcript	I-GENE
+appeared	O
+to	O
+be	O
+at	O
+least	O
+250	O
+-	O
+fold	O
+less	O
+abundant	O
+than	O
+ribosomal	O
+RNA	O
+.	O
+
+One	O
+such	O
+mutant	O
+also	O
+affects	O
+the	O
+overlapping	O
+-	O
+10	O
+hexamer	O
+of	O
+PR	O
+and	O
+results	O
+in	O
+reduced	O
+occupancy	O
+by	O
+both	O
+MerR	B-GENE
+and	O
+RNA	B-GENE
+polymerase	I-GENE
+,	O
+likely	O
+as	O
+a	O
+result	O
+of	O
+inefficient	O
+transcriptional	O
+initiation	O
+of	O
+merR	B-GENE
+mRNA	I-GENE
+.	O
+
+This	O
+promoter	O
+could	O
+direct	O
+the	O
+constitutive	O
+expression	O
+of	O
+the	O
+reporter	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+at	O
+high	O
+frequency	O
+in	O
+transfected	O
+colonies	O
+of	O
+transformed	O
+cells	O
+that	O
+express	O
+L	B-GENE
+-	I-GENE
+plastin	I-GENE
+constitutively	O
+;	O
+by	O
+contrast	O
+,	O
+this	O
+promoter	O
+was	O
+virtually	O
+inactive	O
+in	O
+transfected	O
+colonies	O
+of	O
+normal	O
+fibroblasts	O
+and	O
+it	O
+exhibited	O
+a	O
+low	O
+frequency	O
+of	O
+constitutive	O
+activation	O
+in	O
+transfected	O
+colonies	O
+of	O
+in	O
+vitro	O
+SV40	O
+-	O
+transformed	O
+fibroblasts	O
+which	O
+did	O
+not	O
+exhibit	O
+L	B-GENE
+-	I-GENE
+plastin	I-GENE
+expression	O
+.	O
+
+The	O
+half	O
+-	O
+life	O
+of	O
+the	O
+serum	O
+-	O
+induced	O
+CBP	B-GENE
+/	O
+tk	B-GENE
+binding	O
+activity	O
+was	O
+estimated	O
+to	O
+be	O
+less	O
+than	O
+1	O
+h	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+400	O
+WORDS	O
+)	O
+
+The	O
+gene	O
+includes	O
+three	O
+exons	O
+and	O
+two	O
+introns	O
+within	O
+1	O
+.	O
+6	O
+kilobases	O
+of	O
+DNA	O
+,	O
+and	O
+the	O
+entire	O
+open	O
+reading	O
+frame	O
+for	O
+glycoprotein	B-GENE
+IX	I-GENE
+is	O
+included	O
+within	O
+the	O
+third	O
+exon	O
+.	O
+
+Rhizobium	O
+meliloti	O
+large	O
+plasmid	O
+pRmeGR4b	O
+carries	O
+the	O
+nodulation	O
+competitiveness	O
+locus	O
+nfe	B-GENE
+responsible	O
+for	O
+the	O
+nodulation	O
+efficiency	O
+and	O
+competitive	O
+ability	O
+of	O
+strain	O
+GR4	O
+on	O
+alfalfa	O
+roots	O
+.	O
+
+Further	O
+,	O
+the	O
+ability	O
+of	O
+recombinant	O
+beta	O
+and	O
+/	O
+or	O
+gamma	O
+chains	O
+to	O
+function	O
+in	O
+defined	O
+biochemical	O
+assays	O
+of	O
+beta	O
+gamma	O
+activity	O
+was	O
+assessed	O
+for	O
+membrane	O
+extracts	O
+and	O
+supernatant	O
+fractions	O
+from	O
+infected	O
+Sf9	O
+cells	O
+.	O
+
+This	O
+report	O
+describes	O
+the	O
+identification	O
+of	O
+a	O
+gene	O
+of	O
+related	O
+function	O
+,	O
+SMD1	B-GENE
+,	O
+located	O
+immediately	O
+3	O
+'	O
+to	O
+PRP38	B-GENE
+.	O
+
+These	O
+data	O
+establish	O
+Smd1p	B-GENE
+as	O
+a	O
+required	O
+component	O
+of	O
+the	O
+cellular	O
+splicing	O
+apparatus	O
+and	O
+a	O
+factor	O
+in	O
+snRNA	O
+maturation	O
+and	O
+stability	O
+.	O
+
+This	O
+study	O
+compared	O
+the	O
+gross	O
+and	O
+fine	O
+motor	O
+performance	O
+of	O
+14	O
+traumatically	O
+brain	O
+-	O
+injured	O
+children	O
+(	O
+five	O
+to	O
+15	O
+years	O
+old	O
+,	O
+with	O
+loss	O
+of	O
+consciousness	O
+for	O
+at	O
+least	O
+24	O
+hours	O
+)	O
+to	O
+14	O
+normal	O
+children	O
+group	O
+matched	O
+for	O
+age	O
+and	O
+sex	O
+.	O
+
+We	O
+compared	O
+the	O
+parameters	O
+pleural	B-GENE
+adenosine	I-GENE
+deaminase	I-GENE
+(	O
+PADA	B-GENE
+,	O
+determined	O
+in	O
+405	O
+patients	O
+)	O
+,	O
+the	O
+PADA	B-GENE
+/	O
+serum	B-GENE
+ADA	I-GENE
+ratio	O
+(	O
+P	B-GENE
+/	O
+SADA	B-GENE
+;	O
+276	O
+cases	O
+)	O
+,	O
+pleural	B-GENE
+lysozyme	I-GENE
+(	O
+PLYS	B-GENE
+,	O
+276	O
+cases	O
+)	O
+,	O
+the	O
+PLYS	B-GENE
+/	O
+serum	B-GENE
+LYS	I-GENE
+ratio	O
+(	O
+P	B-GENE
+/	O
+SLYS	B-GENE
+;	O
+276	O
+cases	O
+)	O
+,	O
+and	O
+pleural	B-GENE
+interferon	I-GENE
+gamma	I-GENE
+(	O
+IFN	B-GENE
+,	O
+145	O
+cases	O
+)	O
+regarding	O
+their	O
+ability	O
+to	O
+differentiate	O
+tuberculous	O
+pleural	O
+effusions	O
+from	O
+others	O
+.	O
+
+These	O
+exons	O
+were	O
+identified	O
+by	O
+cloning	O
+and	O
+sequencing	O
+cDNAs	O
+obtained	O
+by	O
+polymerase	O
+chain	O
+reaction	O
+amplification	O
+of	O
+a	O
+fibroblast	O
+cDNA	O
+library	O
+.	O
+
+Deletion	O
+of	O
+the	O
+apeA	B-GENE
+gene	I-GENE
+,	O
+either	O
+with	O
+or	O
+without	O
+deletion	O
+of	O
+other	O
+proteinases	O
+(	O
+protease	B-GENE
+IV	I-GENE
+and	O
+aminopeptidase	B-GENE
+N	I-GENE
+)	O
+,	O
+did	O
+not	O
+have	O
+any	O
+effect	O
+on	O
+cell	O
+growth	O
+in	O
+the	O
+various	O
+media	O
+tested	O
+.	O
+
+In	O
+Experiment	O
+2	O
+scopolamine	O
+hydrobromide	O
+,	O
+0	O
+.	O
+5	O
+and	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+,	O
+was	O
+administered	O
+1	O
+h	O
+before	O
+each	O
+electrical	O
+stimulation	O
+until	O
+each	O
+rat	O
+showed	O
+the	O
+stage	O
+-	O
+3	O
+seizure	O
+.	O
+
+PNT	O
+,	O
+ADD	O
+and	O
+BSS	O
+in	O
+the	O
+initial	O
+stage	O
+of	O
+kindling	O
+,	O
+kindling	O
+rate	O
+for	O
+the	O
+stage	O
+-	O
+3	O
+and	O
+-	O
+5	O
+seizures	O
+,	O
+seizure	O
+parameters	O
+at	O
+the	O
+first	O
+stage	O
+-	O
+3	O
+and	O
+-	O
+5	O
+were	O
+recorded	O
+and	O
+compared	O
+to	O
+the	O
+values	O
+of	O
+saline	O
+-	O
+treated	O
+,	O
+control	O
+group	O
+.	O
+
+CONCLUSIONS	O
+.	O
+
+There	O
+was	O
+a	O
+positive	O
+correlation	O
+between	O
+pyridinium	O
+cross	O
+-	O
+link	O
+excretion	O
+and	O
+thyroid	O
+hormone	O
+concentrations	O
+.	O
+
+Mutations	O
+truncating	O
+as	O
+many	O
+as	O
+143	O
+C	O
+-	O
+terminal	O
+residues	O
+from	O
+the	O
+transcriptional	O
+activator	O
+encoded	O
+by	O
+the	O
+areA	B-GENE
+gene	I-GENE
+,	O
+mediating	O
+nitrogen	O
+metabolite	O
+repression	O
+in	O
+Aspergillus	O
+nidulans	O
+,	O
+do	O
+not	O
+significantly	O
+reduce	O
+the	O
+ability	O
+of	O
+the	O
+areA	B-GENE
+product	I-GENE
+to	O
+activate	O
+expression	O
+of	O
+most	O
+genes	O
+under	O
+areA	B-GENE
+control	O
+.	O
+
+A	O
+region	O
+in	O
+the	O
+C	O
+-	O
+terminus	O
+of	O
+adenovirus	B-GENE
+2	I-GENE
+/	I-GENE
+5	I-GENE
+E1a	I-GENE
+protein	I-GENE
+is	O
+required	O
+for	O
+association	O
+with	O
+a	O
+cellular	O
+phosphoprotein	O
+and	O
+important	O
+for	O
+the	O
+negative	O
+modulation	O
+of	O
+T24	O
+-	O
+ras	B-GENE
+mediated	O
+transformation	O
+,	O
+tumorigenesis	O
+and	O
+metastasis	O
+.	O
+
+These	O
+studies	O
+demonstrate	O
+that	O
+both	O
+G	B-GENE
+alpha	I-GENE
+i	I-GENE
+genes	I-GENE
+are	O
+dynamically	O
+regulated	O
+in	O
+LLC	O
+-	O
+PK1	O
+cells	O
+by	O
+both	O
+growth	O
+,	O
+differentiation	O
+,	O
+and	O
+hormone	O
+signals	O
+.	O
+
+Constructs	O
+containing	O
+the	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+PfCPK	I-GENE
+cDNA	I-GENE
+have	O
+been	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+at	O
+a	O
+high	O
+level	O
+to	O
+generate	O
+a	O
+60	O
+-	O
+kDa	O
+recombinant	O
+protein	O
+.	O
+
+In	O
+mitogen	O
+-	O
+stimulated	O
+splenocytes	O
+,	O
+Gfi	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+begins	O
+to	O
+rise	O
+at	O
+12	O
+h	O
+after	O
+stimulation	O
+and	O
+reaches	O
+very	O
+high	O
+levels	O
+after	O
+50	O
+h	O
+,	O
+suggesting	O
+that	O
+it	O
+may	O
+be	O
+functionally	O
+involved	O
+in	O
+events	O
+occurring	O
+after	O
+the	O
+interaction	O
+of	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+with	O
+its	O
+receptor	O
+,	O
+perhaps	O
+during	O
+the	O
+transition	O
+from	O
+the	O
+G1	O
+to	O
+the	O
+S	O
+phase	O
+of	O
+the	O
+cell	O
+cycle	O
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+characterized	O
+the	O
+GCD6	B-GENE
+and	O
+GCD7	B-GENE
+genes	I-GENE
+and	O
+shown	O
+that	O
+their	O
+products	O
+are	O
+required	O
+to	O
+repress	O
+GCN4	B-GENE
+translation	O
+under	O
+nonstarvation	O
+conditions	O
+.	O
+
+The	O
+plateau	O
+MO2	O
+value	O
+was	O
+that	O
+predicted	O
+by	O
+allometric	O
+relation	O
+.	O
+
+While	O
+the	O
+latter	O
+corresponded	O
+to	O
+a	O
+protein	O
+of	O
+824	O
+amino	O
+acids	O
+,	O
+an	O
+upstream	O
+open	O
+reading	O
+frame	O
+(	O
+uORF	O
+)	O
+within	O
+the	O
+5	O
+'	O
+leader	O
+could	O
+potentially	O
+encode	O
+a	O
+54	O
+amino	O
+acid	O
+peptide	O
+.	O
+
+The	O
+SCH9	B-GENE
+protein	I-GENE
+kinase	I-GENE
+mRNA	I-GENE
+contains	O
+a	O
+long	O
+5	O
+'	O
+leader	O
+with	O
+a	O
+small	O
+open	O
+reading	O
+frame	O
+.	O
+
+In	O
+contrast	O
+to	O
+T	O
+cells	O
+,	O
+in	O
+fibroblasts	O
+PILOT	B-GENE
+gene	I-GENE
+expression	O
+requires	O
+only	O
+one	O
+signal	O
+(	O
+PMA	O
+)	O
+and	O
+is	O
+not	O
+affected	O
+by	O
+CyA	O
+.	O
+
+Histochemical	O
+localization	O
+of	O
+GUS	B-GENE
+revealed	O
+promoter	O
+function	O
+in	O
+leaf	O
+epidermis	O
+,	O
+mesophyll	O
+and	O
+vascular	O
+bundles	O
+,	O
+in	O
+the	O
+cortex	O
+and	O
+vascular	O
+cylinder	O
+of	O
+the	O
+root	O
+.	O
+
+In	O
+order	O
+to	O
+investigate	O
+how	O
+these	O
+expression	O
+patterns	O
+are	O
+established	O
+,	O
+we	O
+fused	O
+promoter	O
+regions	O
+of	O
+an	O
+acidic	O
+and	O
+a	O
+basic	O
+glucanase	B-GENE
+gene	I-GENE
+to	O
+the	O
+beta	B-GENE
+-	I-GENE
+glucuronidase	I-GENE
+(	O
+GUS	B-GENE
+)	O
+reporter	O
+gene	O
+and	O
+examined	O
+expression	O
+of	O
+these	O
+constructs	O
+in	O
+transgenic	O
+tobacco	O
+plants	O
+.	O
+
+Sudomoina	O
+,	O
+A	O
+.	O
+
+Zinc	O
+fingers	O
+(	O
+Zf	O
+)	O
+are	O
+a	O
+common	O
+structural	O
+motif	O
+found	O
+in	O
+many	O
+nucleic	O
+acid	O
+-	O
+binding	O
+proteins	O
+.	O
+
+The	O
+deduced	O
+bovine	O
+EFIA	B-GENE
+#	I-GENE
+1	I-GENE
+amino	O
+acid	O
+(	O
+aa	O
+)	O
+sequence	O
+is	O
+98	O
+%	O
+identical	O
+to	O
+rat	O
+EFIA	B-GENE
+and	O
+100	O
+%	O
+identical	O
+to	O
+human	O
+EFIA	B-GENE
+/	O
+DbpB	B-GENE
+/	O
+YB	B-GENE
+-	I-GENE
+1	I-GENE
+family	O
+member	O
+DNA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+B	I-GENE
+(	O
+DbpB	B-GENE
+)	O
+.	O
+
+Effect	O
+of	O
+tracheal	O
+insufflation	O
+of	O
+deferoxamine	O
+on	O
+acute	O
+ozone	O
+toxicity	O
+in	O
+rats	O
+.	O
+
+Localization	O
+of	O
+the	O
+insertion	O
+locus	O
+in	O
+the	O
+yeast	O
+genome	O
+and	O
+complementation	O
+studies	O
+with	O
+the	O
+temperature	O
+-	O
+sensitive	O
+mutant	O
+indicate	O
+that	O
+the	O
+two	O
+mutations	O
+are	O
+allelic	O
+.	O
+
+Replacement	O
+of	O
+the	O
+spacer	O
+sequence	O
+between	O
+the	O
+two	O
+ARMs	O
+with	O
+a	O
+shorter	O
+stretch	O
+of	O
+sequence	O
+also	O
+reduced	O
+RNA	O
+binding	O
+in	O
+vitro	O
+.	O
+
+Second	O
+,	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+Gal	I-GENE
+-	I-GENE
+ER	I-GENE
+was	O
+rendered	O
+more	O
+potent	O
+and	O
+less	O
+susceptible	O
+to	O
+cell	O
+type	O
+-	O
+specific	O
+variation	O
+by	O
+fusing	O
+the	O
+strong	O
+activating	O
+domain	O
+of	O
+the	O
+herpesvirus	B-GENE
+protein	I-GENE
+VP16	I-GENE
+onto	O
+its	O
+C	O
+terminus	O
+.	O
+
+The	O
+exogenous	O
+fos	B-GENE
+gene	I-GENE
+was	O
+rapidly	O
+induced	O
+to	O
+maximal	O
+levels	O
+within	O
+1	O
+-	O
+2	O
+hr	O
+of	O
+estrogen	O
+addition	O
+.	O
+
+Elimination	O
+of	O
+Haemophilus	O
+influenzae	O
+type	O
+b	O
+meningitis	O
+after	O
+introduction	O
+of	O
+vaccination	O
+
+Endosonography	O
+accurately	O
+assessed	O
+tumor	O
+extension	O
+in	O
+two	O
+T2	O
+tumors	O
+,	O
+14	O
+T3	O
+tumors	O
+,	O
+and	O
+seven	O
+T4	O
+tumors	O
+.	O
+
+Analysis	O
+of	O
+cell	O
+cycle	O
+regulation	O
+in	O
+the	O
+budding	O
+yeast	O
+Saccharomyces	O
+cerevisiae	O
+has	O
+shown	O
+that	O
+a	O
+central	O
+regulatory	O
+protein	O
+kinase	O
+,	O
+Cdc28	B-GENE
+,	O
+undergoes	O
+changes	O
+in	O
+activity	O
+through	O
+the	O
+cell	O
+cycle	O
+by	O
+associating	O
+with	O
+distinct	O
+groups	O
+of	O
+cyclins	B-GENE
+that	O
+accumulate	O
+at	O
+different	O
+times	O
+.	O
+
+Overlapping	O
+clones	O
+representing	O
+full	O
+-	O
+length	O
+cDNAs	O
+for	O
+MMI	B-GENE
+alpha	I-GENE
+were	O
+obtained	O
+from	O
+mouse	O
+brain	O
+.	O
+
+The	O
+method	O
+involves	O
+preliminary	O
+isolation	O
+of	O
+oxiracetam	O
+and	O
+internal	O
+standard	O
+from	O
+plasma	O
+by	O
+solid	O
+-	O
+phase	O
+extraction	O
+prior	O
+to	O
+the	O
+formation	O
+of	O
+their	O
+n	O
+-	O
+propyl	O
+carbamate	O
+derivatives	O
+.	O
+
+Pathways	O
+linking	O
+the	O
+olfactory	O
+bulbs	O
+with	O
+the	O
+medial	O
+preoptic	O
+anterior	O
+hypothalamus	O
+are	O
+important	O
+for	O
+intermale	O
+aggression	O
+in	O
+mice	O
+.	O
+
+In	O
+contrast	O
+,	O
+rats	O
+receiving	O
+U74500A	O
+(	O
+2	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+infusion	O
+commencing	O
+30	O
+min	O
+prior	O
+to	O
+revascularisation	O
+)	O
+exhibited	O
+enhanced	O
+GMBF	O
+throughout	O
+reperfusion	O
+[	O
+PI	O
+10	O
+min	O
+:	O
+3	O
+.	O
+26	O
+(	O
+2	O
+.	O
+56	O
+-	O
+3	O
+.	O
+63	O
+)	O
+;	O
+120	O
+min	O
+:	O
+2	O
+.	O
+03	O
+(	O
+1	O
+.	O
+73	O
+-	O
+2	O
+.	O
+25	O
+)	O
+;	O
+240	O
+min	O
+:	O
+2	O
+.	O
+13	O
+(	O
+1	O
+.	O
+75	O
+-	O
+2	O
+.	O
+44	O
+)	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+vs	O
+.	O
+controls	O
+and	O
+normals	O
+]	O
+with	O
+complete	O
+muscle	O
+salvage	O
+[	O
+GMV	O
+100	O
+%	O
+in	O
+all	O
+reperfused	O
+muscles	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+vs	O
+.	O
+controls	O
+,	O
+not	O
+significant	O
+(	O
+NS	O
+)	O
+vs	O
+.	O
+normals	O
+and	O
+6	O
+h	O
+ischaemia	O
+]	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Sequencing	O
+of	O
+a	O
+1	O
+.	O
+3	O
+-	O
+kilobase	O
+fragment	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+TSG6	B-GENE
+gene	I-GENE
+identified	O
+TATA	O
+-	O
+like	O
+and	O
+CAAT	O
+sequences	O
+near	O
+the	O
+transcription	O
+start	O
+site	O
+.	O
+
+The	O
+region	O
+that	O
+imparts	O
+inducibility	O
+by	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+or	O
+TNF	B-GENE
+(	O
+positions	O
+-	O
+165	O
+to	O
+-	O
+58	O
+)	O
+contains	O
+potential	O
+binding	O
+sites	O
+for	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+and	I-GENE
+-	I-GENE
+2	I-GENE
+,	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+NF	B-GENE
+-	I-GENE
+IL	I-GENE
+-	I-GENE
+6	I-GENE
+.	O
+
+Ig	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	O
+Ig	B-GENE
+-	I-GENE
+beta	I-GENE
+contain	O
+extended	O
+cytoplasmic	O
+structure	O
+(	O
+61	O
+and	O
+48	O
+amino	O
+acids	O
+,	O
+respectively	O
+)	O
+and	O
+associate	O
+with	O
+cytoplasmic	O
+effectors	O
+indicating	O
+that	O
+they	O
+are	O
+directly	O
+involved	O
+in	O
+signal	O
+transduction	O
+.	O
+
+We	O
+studied	O
+the	O
+functional	O
+interaction	O
+between	O
+human	O
+embryonic	O
+zeta	B-GENE
+2	I-GENE
+globin	I-GENE
+promoter	O
+and	O
+the	O
+alpha	B-GENE
+globin	I-GENE
+regulatory	I-GENE
+element	I-GENE
+(	O
+HS	B-GENE
+-	I-GENE
+40	I-GENE
+)	O
+located	O
+40	O
+kb	O
+upstream	O
+of	O
+the	O
+zeta	B-GENE
+2	I-GENE
+globin	I-GENE
+gene	I-GENE
+.	O
+
+It	O
+was	O
+shown	O
+by	O
+transient	O
+expression	O
+assay	O
+that	O
+HS	B-GENE
+-	I-GENE
+40	I-GENE
+behaved	O
+as	O
+an	O
+authentic	O
+enhancer	O
+for	O
+high	O
+-	O
+level	O
+zeta	B-GENE
+2	I-GENE
+globin	I-GENE
+promoter	I-GENE
+activity	O
+in	O
+K562	O
+cells	O
+,	O
+an	O
+erythroid	O
+cell	O
+line	O
+of	O
+embryonic	O
+and	O
+/	O
+or	O
+fetal	O
+origin	O
+.	O
+
+Initial	O
+results	O
+indicate	O
+that	O
+this	O
+23S	B-GENE
+pre	I-GENE
+-	I-GENE
+rRNA	I-GENE
+is	O
+the	O
+same	O
+as	O
+the	O
+species	O
+detected	O
+on	O
+depletion	O
+of	O
+the	O
+small	B-GENE
+nucleolar	I-GENE
+RNA	I-GENE
+-	I-GENE
+associated	I-GENE
+proteins	I-GENE
+NOP1	B-GENE
+and	O
+GAR1	B-GENE
+and	O
+in	O
+an	O
+snr10	B-GENE
+mutant	I-GENE
+strain	O
+.	O
+
+Breitbart	O
+,	O
+L	O
+.	O
+
+This	O
+study	O
+evaluates	O
+the	O
+feasibility	O
+of	O
+indirect	O
+mesenteric	O
+lymphangiography	O
+as	O
+a	O
+colonoscopic	O
+technique	O
+in	O
+a	O
+canine	O
+model	O
+.	O
+
+Internal	O
+amino	O
+acid	O
+sequence	O
+has	O
+now	O
+been	O
+obtained	O
+from	O
+this	O
+protein	O
+which	O
+shares	O
+50	O
+-	O
+100	O
+%	O
+sequence	O
+identity	O
+with	O
+sequences	O
+encoded	O
+by	O
+mammalian	B-GENE
+G	I-GENE
+alpha	I-GENE
+11	I-GENE
+and	O
+G	B-GENE
+alpha	I-GENE
+q	I-GENE
+cDNAs	I-GENE
+.	O
+
+Estradiol	O
+is	O
+known	O
+to	O
+induce	O
+expression	O
+of	O
+certain	O
+proto	O
+-	O
+oncogenes	O
+,	O
+and	O
+this	O
+led	O
+us	O
+to	O
+examine	O
+potential	O
+regulatory	O
+regions	O
+of	O
+the	O
+cellular	B-GENE
+c	I-GENE
+-	I-GENE
+fos	I-GENE
+oncogene	I-GENE
+.	O
+
+Air	O
+lead	O
+was	O
+not	O
+a	O
+significant	O
+explanatory	O
+variable	O
+.	O
+
+We	O
+now	O
+show	O
+that	O
+regulation	O
+of	O
+flaN	B-GENE
+transcription	O
+in	O
+vivo	O
+depends	O
+on	O
+a	O
+sigma	B-GENE
+54	I-GENE
+promoter	I-GENE
+and	O
+two	O
+ftr	O
+elements	O
+located	O
+downstream	O
+of	O
+the	O
+transcription	O
+start	O
+site	O
+at	O
++	O
+86	O
+(	O
+ftr2	O
+)	O
+and	O
++	O
+120	O
+(	O
+ftr3	O
+)	O
+.	O
+
+Fibular	O
+dimelia	O
+with	O
+deficiency	O
+of	O
+the	O
+tibia	O
+.	O
+
+This	O
+prospective	O
+study	O
+compared	O
+the	O
+measured	O
+energy	O
+expenditures	O
+of	O
+30	O
+patients	O
+using	O
+indirect	O
+calorimetry	O
+with	O
+their	O
+predicted	O
+basal	O
+energy	O
+expenditure	O
+according	O
+to	O
+the	O
+Harris	O
+-	O
+Benedict	O
+equation	O
+,	O
+or	O
+their	O
+calculated	O
+energy	O
+expenditure	O
+derived	O
+from	O
+basal	O
+energy	O
+expenditure	O
+times	O
+,	O
+an	O
+activity	O
+factor	O
+,	O
+and	O
+a	O
+stress	O
+factor	O
+.	O
+
+However	O
+,	O
+after	O
+repeated	O
+infections	O
+,	O
+hypobiotic	O
+larvae	O
+were	O
+numerous	O
+.	O
+
+This	O
+was	O
+performed	O
+in	O
+a	O
+double	O
+blinded	O
+,	O
+randomized	O
+,	O
+placebo	O
+-	O
+controlled	O
+study	O
+.	O
+
+Group	O
+I	O
+consisted	O
+of	O
+six	O
+noncholestatic	O
+patients	O
+;	O
+group	O
+II	O
+consisted	O
+of	O
+nine	O
+mildly	O
+cholestatic	O
+patients	O
+with	O
+mild	O
+hepatic	O
+impairment	O
+(	O
+conjugated	O
+bilirubin	O
+,	O
+47	O
+mumol	O
+liter	O
+-	O
+1	O
+;	O
+alkaline	B-GENE
+phosphatase	I-GENE
+,	O
+280	O
+IU	O
+liter	O
+-	O
+1	O
+;	O
+gamma	B-GENE
+-	I-GENE
+glutamyltranspeptidase	I-GENE
+,	O
+190	O
+IU	O
+liter	O
+-	O
+1	O
+)	O
+;	O
+group	O
+III	O
+consisted	O
+of	O
+six	O
+benign	O
+intrahepatic	O
+cholestatic	O
+patients	O
+with	O
+high	O
+isolated	O
+conjugated	O
+hyperbilirubinemia	O
+(	O
+98	O
+.	O
+1	O
+mumol	O
+liter	O
+-	O
+1	O
+)	O
+.	O
+
+There	O
+was	O
+either	O
+no	O
+change	O
+or	O
+an	O
+improvement	O
+in	O
+renographic	O
+findings	O
+(	O
+t1	O
+/	O
+2	O
+time	O
+and	O
+/	O
+or	O
+split	O
+function	O
+)	O
+in	O
+40	O
+patients	O
+(	O
+93	O
+%	O
+)	O
+.	O
+
+We	O
+discuss	O
+the	O
+need	O
+to	O
+use	O
+animals	O
+older	O
+than	O
+3	O
+months	O
+for	O
+the	O
+study	O
+of	O
+'	O
+adult	O
+'	O
+regeneration	O
+phenomena	O
+since	O
+3	O
+-	O
+month	O
+-	O
+old	O
+rats	O
+may	O
+be	O
+somewhat	O
+immature	O
+.	O
+
+Nuclear	B-GENE
+beta	I-GENE
+II	I-GENE
+PKC	I-GENE
+,	O
+like	O
+p34cdc2	B-GENE
+kinase	I-GENE
+,	O
+may	O
+function	O
+to	O
+regulate	O
+nuclear	O
+lamina	O
+structural	O
+stability	O
+during	O
+cell	O
+cycle	O
+.	O
+
+In	O
+situ	O
+copper	O
+-	O
+phenanthroline	O
+footprinting	O
+of	O
+individual	O
+gel	O
+shift	O
+assembly	O
+intermediates	O
+shows	O
+that	O
+on	O
+the	O
+302	O
+-	O
+nucleotide	O
+G4oric	O
+,	O
+the	O
+first	O
+two	O
+SSB	B-GENE
+tetramers	I-GENE
+assemble	O
+at	O
+random	O
+,	O
+but	O
+the	O
+addition	O
+of	O
+more	O
+SSB	B-GENE
+tetramers	I-GENE
+results	O
+in	O
+formation	O
+of	O
+a	O
+unique	O
+structure	O
+.	O
+
+Effects	O
+of	O
+intramammary	O
+endotoxin	O
+infusion	O
+on	O
+milking	O
+-	O
+induced	O
+oxytocin	B-GENE
+release	O
+.	O
+
+A	O
+rat	O
+cDNA	O
+that	O
+encodes	O
+eIF	B-GENE
+-	I-GENE
+5	I-GENE
+has	O
+been	O
+isolated	O
+and	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+to	O
+yield	O
+a	O
+catalytically	O
+active	O
+eIF	B-GENE
+-	I-GENE
+5	I-GENE
+protein	I-GENE
+.	O
+
+In	O
+F42A	O
+-	O
+stimulated	O
+internalization	O
+assays	O
+on	O
+forskolin	O
+-	O
+induced	O
+YT	O
+-	O
+1	O
+cells	O
+,	O
+the	O
+IL	B-GENE
+-	I-GENE
+2R	I-GENE
+alpha	I-GENE
+chain	I-GENE
+is	O
+consistently	O
+endocytosed	O
+together	O
+with	O
+the	O
+IL	B-GENE
+-	I-GENE
+2R	I-GENE
+beta	I-GENE
+subunit	I-GENE
+indicating	O
+that	O
+IL	B-GENE
+-	I-GENE
+2R	I-GENE
+alpha	I-GENE
+is	O
+stably	O
+associated	O
+with	O
+the	O
+F42A	B-GENE
+-	I-GENE
+IL	I-GENE
+-	I-GENE
+2R	I-GENE
+beta	I-GENE
+complex	I-GENE
+even	O
+though	O
+the	O
+alpha	O
+-	O
+subunit	O
+contributes	O
+little	O
+if	O
+any	O
+affinity	O
+to	O
+the	O
+F42A	O
+binding	O
+reaction	O
+.	O
+
+The	O
+microcirculatory	O
+dynamics	O
+of	O
+prostaglandin	O
+E1	O
+and	O
+/	O
+or	O
+nicardipine	O
+and	O
+their	O
+different	O
+reactions	O
+in	O
+the	O
+hyper	O
+-	O
+and	O
+hypodynamic	O
+state	O
+of	O
+septic	O
+shock	O
+in	O
+a	O
+rat	O
+model	O
+
+The	O
+short	O
+-	O
+term	O
+synthesis	O
+and	O
+infant	O
+-	O
+regulated	O
+removal	O
+of	O
+milk	O
+in	O
+lactating	O
+women	O
+.	O
+
+Based	O
+on	O
+these	O
+results	O
+,	O
+a	O
+new	O
+model	O
+for	O
+the	O
+regulation	O
+of	O
+nif	B-GENE
+/	O
+fix	B-GENE
+gene	O
+expression	O
+in	O
+A	O
+.	O
+caulinodans	O
+is	O
+proposed	O
+.	O
+
+Nitric	O
+oxide	O
+inhalation	O
+selectively	O
+reduces	O
+pulmonary	O
+hypertension	O
+in	O
+porcine	O
+endotoxin	O
+shock	O
+and	O
+improves	O
+arterial	O
+oxygenation	O
+and	O
+pH	O
+with	O
+a	O
+marked	O
+attenuation	O
+of	O
+sympathetic	O
+activation	O
+.	O
+
+B	O
+cell	O
+-	O
+specific	O
+mb	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+B29	B-GENE
+genes	I-GENE
+encode	O
+the	O
+alpha	O
+/	O
+beta	O
+components	O
+of	O
+the	O
+BCR	B-GENE
+-	I-GENE
+associated	I-GENE
+complex	I-GENE
+in	O
+mature	O
+sIgM	B-GENE
++	I-GENE
+B	O
+cells	O
+.	O
+
+Bipolarity	O
+in	O
+Jungian	O
+type	O
+theory	O
+and	O
+the	O
+Myers	O
+-	O
+Briggs	O
+Type	O
+Indicator	O
+.	O
+
+A	O
+variety	O
+of	O
+nuclear	O
+ribonucleoproteins	O
+are	O
+believed	O
+to	O
+associate	O
+directly	O
+with	O
+nascent	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+transcripts	I-GENE
+and	O
+remain	O
+associated	O
+during	O
+subsequent	O
+nuclear	O
+RNA	O
+processing	O
+reactions	O
+,	O
+including	O
+pre	O
+-	O
+mRNA	O
+polyadenylation	O
+and	O
+splicing	O
+as	O
+well	O
+as	O
+nucleocytoplasmic	O
+mRNA	O
+transport	O
+.	O
+
+Mutations	O
+at	O
+three	O
+sites	O
+have	O
+larger	O
+effects	O
+in	O
+muscle	O
+than	O
+nonmuscle	O
+cells	O
+;	O
+an	O
+A	O
+/	O
+T	O
+-	O
+rich	O
+site	O
+mutation	O
+has	O
+a	O
+pronounced	O
+effect	O
+in	O
+both	O
+striated	O
+muscle	O
+types	O
+,	O
+mutations	O
+at	O
+the	O
+MEF1	B-GENE
+(	I-GENE
+Right	I-GENE
+E	I-GENE
+-	I-GENE
+box	I-GENE
+)	I-GENE
+site	I-GENE
+are	O
+relatively	O
+specific	O
+to	O
+expression	O
+in	O
+skeletal	O
+muscle	O
+,	O
+and	O
+mutations	O
+at	O
+the	O
+CArG	O
+site	O
+are	O
+relatively	O
+specific	O
+to	O
+expression	O
+in	O
+cardiac	O
+muscle	O
+.	O
+
+Transient	O
+transfection	O
+analysis	O
+with	O
+these	O
+mutations	O
+revealed	O
+that	O
+only	O
+a	O
+10	O
+-	O
+bp	O
+region	O
+,	O
+containing	O
+precisely	O
+the	O
+Ets	B-GENE
+and	O
+proximal	O
+LyF	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+sites	I-GENE
+,	O
+was	O
+needed	O
+for	O
+D	O
+'	O
+activity	O
+.	O
+
+However	O
+,	O
+despite	O
+its	O
+relationship	O
+to	O
+the	O
+TR	B-GENE
+,	O
+Rev	B-GENE
+-	O
+Erb	B-GENE
+bound	O
+poorly	O
+to	O
+TR	B-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+We	O
+report	O
+here	O
+that	O
+a	O
+25	O
+-	O
+bp	O
+promoter	O
+element	O
+previously	O
+shown	O
+to	O
+be	O
+important	O
+for	O
+the	O
+G1	O
+-	O
+S	O
+activation	O
+of	O
+the	O
+human	B-GENE
+thymidine	I-GENE
+kinase	I-GENE
+(	O
+htk	B-GENE
+)	O
+promoter	O
+in	O
+growth	O
+-	O
+stimulated	O
+cells	O
+is	O
+a	O
+cellular	O
+target	O
+of	O
+cyclin	B-GENE
+A	I-GENE
+and	O
+the	O
+p33cdk2	B-GENE
+complexes	I-GENE
+.	O
+
+These	O
+protective	O
+influences	O
+were	O
+observed	O
+throughout	O
+the	O
+range	O
+of	O
+filling	O
+pressures	O
+measured	O
+,	O
+from	O
+0	O
+to	O
+30	O
+mmHg	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+with	O
+rat	O
+liver	O
+nuclear	O
+extracts	O
+identified	O
+7	O
+major	O
+protein	O
+-	O
+binding	O
+domains	O
+termed	O
+P1	O
+through	O
+P7	O
+in	O
+a	O
+796	O
+base	O
+pair	O
+DNA	O
+fragment	O
+(	O
+base	O
+pairs	O
+-	O
+763	O
+to	O
++	O
+33	O
+)	O
+.	O
+
+Neither	O
+clone	O
+encoded	O
+the	O
+cognate	O
+endonuclease	O
+.	O
+
+The	O
+nifJ	B-GENE
+and	O
+nifH	B-GENE
+promoters	I-GENE
+of	I-GENE
+Klebsiella	I-GENE
+pneumoniae	I-GENE
+are	O
+divergently	O
+transcribed	O
+sigma	B-GENE
+54	I-GENE
+-	I-GENE
+dependent	I-GENE
+promoters	I-GENE
+that	O
+are	O
+positively	O
+activated	O
+by	O
+the	O
+NifA	B-GENE
+protein	I-GENE
+.	O
+
+Both	O
+inhaled	O
+and	O
+superfused	O
+isoflurane	O
+dilated	O
+the	O
+baseline	O
+vein	O
+diameter	O
+before	O
+stimulation	O
+.	O
+
+Prevalence	O
+of	O
+rheumatoid	O
+arthritis	O
+and	O
+rheumatoid	B-GENE
+factor	I-GENE
+in	O
+women	O
+:	O
+evidence	O
+for	O
+a	O
+secular	O
+decline	O
+.	O
+
+Although	O
+olfactory	O
+associative	O
+conditioning	O
+in	O
+newborn	O
+rats	O
+produces	O
+marked	O
+structural	O
+and	O
+functional	O
+changes	O
+in	O
+the	O
+olfactory	O
+bulb	O
+,	O
+recent	O
+evidence	O
+suggests	O
+that	O
+extrabulbar	O
+circuits	O
+must	O
+be	O
+involved	O
+in	O
+storing	O
+these	O
+early	O
+memories	O
+.	O
+
+The	O
+fission	B-GENE
+yeast	I-GENE
+dsk1	I-GENE
++	I-GENE
+gene	I-GENE
+,	O
+a	O
+multicopy	O
+suppressor	O
+for	O
+cold	O
+-	O
+sensitive	O
+dis1	B-GENE
+mutants	I-GENE
+,	O
+encodes	O
+a	O
+novel	O
+61	O
+-	O
+kd	O
+protein	O
+kinase	O
+.	O
+
+Closure	O
+of	O
+the	O
+patent	O
+ductus	O
+arteriosus	O
+with	O
+a	O
+Ligaclip	O
+through	O
+a	O
+minithoracotomy	O
+.	O
+
+Sequence	O
+comparison	O
+between	O
+the	O
+translated	O
+ORF	O
+and	O
+a	O
+protein	O
+database	O
+reveal	O
+between	O
+26	O
+.	O
+5	O
+and	O
+23	O
+.	O
+4	O
+%	O
+aa	O
+sequence	O
+homology	O
+to	O
+bacterial	B-GENE
+transmembrane	I-GENE
+(	I-GENE
+TM	I-GENE
+)	I-GENE
+proteins	I-GENE
+including	O
+those	O
+mediating	O
+chloramphenicol	O
+(	O
+Cm	O
+)	O
+and	O
+tetracycline	O
+(	O
+Tc	O
+)	O
+resistance	O
+and	O
+an	O
+arabinose	O
+-	O
+proton	O
+symport	O
+protein	O
+.	O
+
+The	O
+strategies	O
+by	O
+which	O
+hepatitis	O
+B	O
+and	O
+hepatitis	O
+D	O
+can	O
+be	O
+diminished	O
+and	O
+eventually	O
+eliminated	O
+are	O
+:	O
+immunization	O
+,	O
+measures	O
+to	O
+prevent	O
+exposure	O
+to	O
+infective	O
+blood	O
+or	O
+blood	O
+derivatives	O
+and	O
+education	O
+(	O
+in	O
+particular	O
+awareness	O
+that	O
+hepatitis	O
+B	O
+is	O
+a	O
+sexually	O
+transmitted	O
+disease	O
+)	O
+.	O
+
+The	O
+technical	O
+construction	O
+of	O
+the	O
+mouth	O
+protectors	O
+is	O
+illustrated	O
+,	O
+as	O
+is	O
+the	O
+need	O
+for	O
+instrumentation	O
+and	O
+its	O
+costs	O
+and	O
+the	O
+materials	O
+required	O
+to	O
+manufacture	O
+these	O
+mouth	O
+protectors	O
+.	O
+
+Three	O
+patients	O
+had	O
+well	O
+-	O
+,	O
+6	O
+patients	O
+had	O
+moderately	O
+-	O
+,	O
+and	O
+5	O
+patients	O
+had	O
+poorly	O
+-	O
+differentiated	O
+adenocarcinoma	O
+of	O
+the	O
+prostate	O
+.	O
+
+Spontaneous	O
+burst	O
+firing	O
+in	O
+cat	O
+primary	O
+auditory	O
+cortex	O
+:	O
+age	O
+and	O
+depth	O
+dependence	O
+and	O
+its	O
+effect	O
+on	O
+neural	O
+interaction	O
+measures	O
+.	O
+
+By	O
+applying	O
+the	O
+potentiometric	O
+method	O
+,	O
+in	O
+aqueous	O
+medium	O
+of	O
+ionic	O
+strength	O
+mu	O
+=	O
+0	O
+.	O
+2	O
+,	O
+the	O
+stability	O
+constants	O
+,	O
+log	O
+beta	O
+1	O
+=	O
+4	O
+.	O
+42	O
+and	O
+log	O
+beta	O
+2	O
+=	O
+8	O
+.	O
+57	O
+were	O
+obtained	O
+.	O
+
+Cryopreservation	O
+straws	O
+filled	O
+with	O
+media	O
+plus	O
+additive	O
+are	O
+emersed	O
+below	O
+the	O
+surface	O
+of	O
+an	O
+unprocessed	O
+donor	O
+ejaculate	O
+.	O
+
+The	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+can	O
+potentially	O
+encode	O
+26	O
+-	O
+and	O
+22	O
+-	O
+kDa	O
+proteins	O
+that	O
+differ	O
+only	O
+in	O
+their	O
+carboxyl	O
+tails	O
+because	O
+of	O
+an	O
+alternative	O
+splicing	O
+mechanism	O
+.	O
+
+The	O
+active	O
+open	O
+reading	O
+frame	O
+in	O
+the	O
+clone	O
+maps	O
+at	O
+27	O
+min	O
+on	O
+the	O
+E	O
+.	O
+coli	O
+chromosome	O
+and	O
+is	O
+identical	O
+in	O
+sequence	O
+to	O
+a	O
+wild	O
+type	O
+counterpart	O
+.	O
+
+Subsequent	O
+cloning	O
+and	O
+nucleotide	O
+sequence	O
+analysis	O
+of	O
+the	O
+S	B-GENE
+.	I-GENE
+pombe	I-GENE
+adenylate	I-GENE
+kinase	I-GENE
+gene	I-GENE
+,	O
+adk1	B-GENE
+,	O
+revealed	O
+a	O
+coding	O
+region	O
+of	O
+660	O
+nucleotides	O
+.	O
+
+As	O
+a	O
+result	O
+of	O
+alternative	O
+splicing	O
+,	O
+the	O
+BGP	B-GENE
+gene	I-GENE
+is	O
+transcribed	O
+into	O
+at	O
+least	O
+seven	O
+distinct	O
+mRNA	O
+species	O
+.	O
+
+However	O
+,	O
+essential	O
+contrast	O
+differences	O
+existing	O
+between	O
+the	O
+FSE	O
+sequences	O
+and	O
+their	O
+routine	O
+asymmetric	O
+dual	O
+SE	O
+counterpart	O
+can	O
+be	O
+identified	O
+.	O
+
+The	O
+level	O
+of	O
+the	O
+SUP4A53T61	B-GENE
+transcript	I-GENE
+was	O
+threefold	O
+higher	O
+in	O
+the	O
+tap1	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+than	O
+in	O
+the	O
+wild	O
+type	O
+.	O
+
+This	O
+sequence	O
+similarity	O
+raises	O
+the	O
+possibility	O
+that	O
+GCN1	B-GENE
+interacts	O
+with	O
+ribosomes	O
+or	O
+tRNA	O
+molecules	O
+and	O
+functions	O
+in	O
+conjunction	O
+with	O
+GCN2	B-GENE
+in	O
+monitoring	O
+uncharged	O
+tRNA	O
+levels	O
+during	O
+the	O
+process	O
+of	O
+translation	O
+elongation	O
+.	O
+
+NF	B-GENE
+-	I-GENE
+HB	I-GENE
+(	O
+BSAP	B-GENE
+)	O
+is	O
+a	O
+repressor	O
+of	O
+the	O
+murine	B-GENE
+immunoglobulin	I-GENE
+heavy	I-GENE
+-	I-GENE
+chain	I-GENE
+3	I-GENE
+'	I-GENE
+alpha	I-GENE
+enhancer	I-GENE
+at	O
+early	O
+stages	O
+of	O
+B	O
+-	O
+cell	O
+differentiation	O
+.	O
+
+In	O
+conclusion	O
+,	O
+changes	O
+in	O
+carotid	O
+sinus	O
+stimulation	O
+alters	O
+blood	O
+flow	O
+to	O
+the	O
+hindlimb	O
+through	O
+changes	O
+in	O
+both	O
+Pcrit	O
+and	O
+Ra	O
+.	O
+
+Multizone	O
+PRK	O
+has	O
+been	O
+suggested	O
+to	O
+increase	O
+the	O
+predictability	O
+of	O
+higher	O
+myopic	O
+corrections	O
+.	O
+
+In	O
+17	O
+patients	O
+with	O
+deletions	O
+,	O
+the	O
+parental	O
+origin	O
+of	O
+deletion	O
+was	O
+determined	O
+.	O
+
+The	O
+COL7A1	B-GENE
+gene	I-GENE
+,	O
+which	O
+encodes	O
+type	B-GENE
+VII	I-GENE
+collagen	I-GENE
+,	O
+has	O
+been	O
+implicated	O
+as	O
+a	O
+candidate	O
+gene	O
+for	O
+dominantly	O
+and	O
+recessively	O
+inherited	O
+forms	O
+of	O
+dystrophic	O
+epidermolysis	O
+bullosa	O
+.	O
+
+However	O
+,	O
+study	O
+of	O
+the	O
+productive	O
+gamma	O
+gene	O
+showed	O
+that	O
+the	O
+skipped	O
+variable	O
+exon	O
+was	O
+bounded	O
+by	O
+normal	O
+splicing	O
+signals	O
+and	O
+that	O
+the	O
+adjacent	O
+intron	O
+organization	O
+was	O
+not	O
+altered	O
+.	O
+
+We	O
+conclude	O
+that	O
+grade	O
+III	O
+BGCT	O
+can	O
+be	O
+treated	O
+by	O
+modified	O
+intralesional	O
+excision	O
+provided	O
+the	O
+articular	O
+surfaces	O
+and	O
+part	O
+of	O
+the	O
+metaphysis	O
+are	O
+intact	O
+.	O
+
+Second	O
+,	O
+nitrate	O
+induction	O
+of	O
+aeg	B-GENE
+-	I-GENE
+46	I-GENE
+.	I-GENE
+5	I-GENE
+operon	I-GENE
+expression	O
+is	O
+substantially	O
+enhanced	O
+in	O
+narL	B-GENE
+null	O
+strains	O
+(	O
+M	O
+.	O
+H	O
+.	O
+
+This	O
+new	O
+knowledge	O
+has	O
+contributed	O
+to	O
+the	O
+development	O
+of	O
+a	O
+successful	O
+immunoprophylactic	O
+strategy	O
+for	O
+eliminating	O
+Hib	O
+disease	O
+.	O
+
+The	O
+HMG	B-GENE
+CoA	I-GENE
+reductase	I-GENE
+inhibitors	O
+are	O
+the	O
+most	O
+effective	O
+cholesterol	O
+-	O
+lowering	O
+agents	O
+currently	O
+available	O
+.	O
+
+The	O
+etiology	O
+,	O
+pathology	O
+,	O
+brain	O
+CT	O
+scan	O
+features	O
+,	O
+clinical	O
+manifestations	O
+and	O
+treatment	O
+of	O
+these	O
+accidents	O
+were	O
+discussed	O
+.	O
+
+Drosophila	O
+230	O
+-	O
+kD	O
+TFIID	B-GENE
+subunit	O
+,	O
+a	O
+functional	O
+homolog	O
+of	O
+the	O
+human	O
+cell	O
+cycle	O
+gene	O
+product	O
+,	O
+negatively	O
+regulates	O
+DNA	O
+binding	O
+of	O
+the	O
+TATA	B-GENE
+box	I-GENE
+-	I-GENE
+binding	I-GENE
+subunit	I-GENE
+of	I-GENE
+TFIID	I-GENE
+.	O
+
+One	O
+enigmatic	O
+aspect	O
+of	O
+GATA	B-GENE
+factor	I-GENE
+expression	O
+is	O
+that	O
+several	O
+GATA	B-GENE
+proteins	I-GENE
+,	O
+which	O
+ostensibly	O
+share	O
+the	O
+same	O
+DNA	O
+-	O
+binding	O
+site	O
+specificity	O
+,	O
+are	O
+coexpressed	O
+in	O
+erythroid	O
+cells	O
+.	O
+
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+a	O
+tissue	O
+-	O
+specific	O
+POU	B-GENE
+domain	I-GENE
+factor	I-GENE
+obligatory	O
+for	O
+the	O
+appearance	O
+of	O
+three	O
+cell	O
+phenotypes	O
+in	O
+the	O
+anterior	O
+pituitary	O
+gland	O
+.	O
+
+Maximum	O
+number	O
+of	O
+strains	O
+(	O
+39	O
+.	O
+1	O
+%	O
+)	O
+were	O
+resistant	O
+in	O
+S	O
+.	O
+bareilly	O
+serotype	O
+,	O
+followed	O
+by	O
+S	O
+.	O
+typhimurium	O
+(	O
+21	O
+.	O
+7	O
+%	O
+)	O
+and	O
+least	O
+in	O
+S	O
+.	O
+typhi	O
+(	O
+17	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+Characterization	O
+and	O
+hormonal	O
+regulation	O
+of	O
+the	O
+promoter	O
+of	O
+the	O
+rat	B-GENE
+prostaglandin	I-GENE
+endoperoxide	I-GENE
+synthase	I-GENE
+2	I-GENE
+gene	I-GENE
+in	O
+granulosa	O
+cells	O
+.	O
+
+The	O
+retention	O
+of	O
+75SeHCAT	O
+was	O
+low	O
+.	O
+
+Members	O
+of	O
+the	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+family	I-GENE
+of	O
+basic	B-GENE
+-	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+(	I-GENE
+bZip	I-GENE
+)	I-GENE
+transcription	I-GENE
+factors	I-GENE
+form	O
+heterodimers	O
+and	O
+bind	O
+to	O
+the	O
+CAAT	O
+box	O
+and	O
+other	O
+sequence	O
+-	O
+related	O
+enhancer	O
+motifs	O
+.	O
+
+In	O
+mammalian	O
+cells	O
+,	O
+phosphorylation	O
+of	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+inhibits	O
+the	O
+activity	O
+of	O
+eIF	B-GENE
+-	I-GENE
+2B	I-GENE
+,	O
+the	O
+GDP	B-GENE
+-	I-GENE
+GTP	I-GENE
+exchange	I-GENE
+factor	I-GENE
+for	O
+eIF	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+In	O
+conclusion	O
+,	O
+these	O
+observations	O
+demonstrated	O
+that	O
+stratification	O
+of	O
+acute	O
+MI	O
+patients	O
+by	O
+plasma	O
+ANF	B-GENE
+level	O
+is	O
+a	O
+useful	O
+non	O
+-	O
+invasive	O
+method	O
+for	O
+predicting	O
+prognosis	O
+and	O
+for	O
+identifying	O
+individuals	O
+at	O
+high	O
+risk	O
+of	O
+cardiac	O
+death	O
+.	O
+
+Analysis	O
+of	O
+the	O
+binding	O
+of	O
+Lrp	B-GENE
+to	O
+a	O
+set	O
+of	O
+circularly	O
+permuted	O
+DNA	O
+fragments	O
+from	O
+this	O
+region	O
+indicates	O
+that	O
+Lrp	B-GENE
+induces	O
+DNA	O
+bending	O
+.	O
+
+Seven	O
+out	O
+of	O
+34	O
+patients	O
+died	O
+,	O
+giving	O
+a	O
+mortality	O
+rate	O
+of	O
+21	O
+%	O
+.	O
+
+A	O
+36	O
+-	O
+kDa	O
+protein	O
+that	O
+was	O
+localized	O
+to	O
+the	O
+membrane	O
+fraction	O
+was	O
+detected	O
+in	O
+minicells	O
+containing	O
+plasmids	O
+with	O
+the	O
+ftsN	B-GENE
+gene	I-GENE
+,	O
+confirming	O
+that	O
+FtsN	B-GENE
+was	O
+a	O
+membrane	O
+protein	O
+.	O
+
+SSG1	B-GENE
+,	O
+a	O
+gene	O
+encoding	O
+a	O
+sporulation	B-GENE
+-	I-GENE
+specific	I-GENE
+1	I-GENE
+,	I-GENE
+3	I-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+glucanase	I-GENE
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Expression	O
+of	O
+this	O
+protein	O
+in	O
+E	O
+.	O
+coli	O
+demonstrated	O
+that	O
+tyrosine	O
+was	O
+incorporated	O
+during	O
+suppression	O
+and	O
+that	O
+yeast	B-GENE
+cytoplasmic	I-GENE
+TyrRS	I-GENE
+activity	O
+was	O
+produced	O
+.	O
+
+The	O
+first	O
+involved	O
+complementation	O
+of	O
+a	O
+nonphotosynthetic	O
+mutant	O
+of	O
+Chlamydomonas	O
+,	O
+CC	O
+-	O
+2341	O
+(	O
+ac	O
+-	O
+u	O
+-	O
+g	O
+-	O
+2	O
+.	O
+3	O
+)	O
+,	O
+which	O
+has	O
+a	O
+frameshift	O
+mutation	O
+in	O
+the	O
+psaB	B-GENE
+gene	I-GENE
+,	O
+and	O
+selection	O
+of	O
+photosynthetic	O
+transformants	O
+on	O
+minimal	O
+medium	O
+.	O
+
+Against	O
+200	O
+strains	O
+of	O
+methicillin	O
+-	O
+resistant	O
+Staphylococcus	O
+aureus	O
+(	O
+MRSA	O
+)	O
+isolated	O
+from	O
+1990	O
+to	O
+1991	O
+,	O
+minimum	O
+inhibitory	O
+concentrations	O
+(	O
+MICs	O
+)	O
+of	O
+a	O
+total	O
+of	O
+15	O
+antibacterial	O
+agents	O
+including	O
+arbekacin	O
+(	O
+ABK	O
+)	O
+were	O
+determined	O
+.	O
+
+It	O
+is	O
+reported	O
+that	O
+,	O
+at	O
+present	O
+,	O
+most	O
+of	O
+the	O
+MRSAs	O
+spreading	O
+in	O
+Japan	O
+are	O
+acceleratedly	O
+acquiring	O
+resistance	O
+to	O
+many	O
+drugs	O
+,	O
+and	O
+especially	O
+,	O
+they	O
+are	O
+developing	O
+high	O
+resistance	O
+against	O
+beta	O
+-	O
+lactams	O
+.	O
+
+Beg2	B-GENE
+and	O
+Beg1	B-GENE
+are	O
+regulated	O
+differently	O
+which	O
+may	O
+indicate	O
+variation	O
+in	O
+storage	O
+or	O
+utilization	O
+properties	O
+among	O
+the	O
+barley	B-GENE
+globulins	I-GENE
+.	O
+
+Here	O
+,	O
+we	O
+have	O
+more	O
+closely	O
+investigated	O
+transactivation	O
+of	O
+the	O
+human	B-GENE
+HSP70	I-GENE
+promoter	I-GENE
+by	O
+Myb	B-GENE
+proteins	I-GENE
+.	O
+
+We	O
+have	O
+found	O
+out	O
+that	O
+one	O
+-	O
+year	O
+-	O
+old	O
+carps	O
+are	O
+extremely	O
+sensitive	O
+to	O
+ichthiomycin	O
+in	O
+concentrations	O
+between	O
+25	O
+-	O
+125	O
+micrograms	O
+/	O
+dm3	O
+.	O
+
+RESULTS	O
+:	O
+Statistically	O
+significant	O
+differences	O
+were	O
+obtained	O
+between	O
+group	O
+I	O
+and	O
+II	O
+concerning	O
+the	O
+number	O
+of	O
+patients	O
+in	O
+whom	O
+induced	O
+atrial	O
+fibrillation	O
+with	O
+conduction	O
+by	O
+the	O
+accessory	O
+pathway	O
+and	O
+RR	O
+<	O
+or	O
+=	O
+250	O
+msec	O
+was	O
+found	O
+(	O
+0	O
+vs	O
+6	O
+,	O
+p	O
+=	O
+0	O
+.	O
+0045	O
+)	O
+.	O
+
+We	O
+studied	O
+the	O
+effect	O
+of	O
+skinfold	O
+thickness	O
+on	O
+the	O
+correlation	O
+between	O
+serum	O
+total	O
+bilirubin	O
+level	O
+and	O
+transcutaneous	O
+bilirubin	O
+(	O
+TcB	O
+)	O
+readings	O
+.	O
+
+The	O
+GTPase	B-GENE
+activity	O
+of	O
+CDC42Ce	B-GENE
+is	O
+moderately	O
+stimulated	O
+by	O
+human	B-GENE
+n	I-GENE
+-	I-GENE
+chimaerin	I-GENE
+,	O
+a	O
+GTPase	B-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+for	O
+the	O
+related	O
+p21	B-GENE
+rac1	B-GENE
+.	O
+
+Tl	O
+-	O
+201	O
+uptake	O
+ratio	O
+of	O
+the	O
+right	O
+ventricle	O
+,	O
+which	O
+represents	O
+the	O
+ratio	O
+of	O
+total	O
+counts	O
+of	O
+the	O
+right	O
+ventricle	O
+to	O
+counts	O
+of	O
+the	O
+administered	O
+dose	O
+of	O
+Tl	O
+-	O
+201	O
+,	O
+was	O
+higher	O
+in	O
+COPD	O
+,	O
+especially	O
+in	O
+pulmonary	O
+emphysema	O
+and	O
+B	O
+type	O
+COPD	O
+by	O
+Burrows	O
+classification	O
+than	O
+in	O
+controls	O
+.	O
+
+A	O
+second	O
+hydrophobic	O
+domain	O
+,	O
+bordered	O
+by	O
+two	O
+hydrophilic	O
+regions	O
+strongly	O
+suggests	O
+a	O
+transmembrane	O
+region	O
+.	O
+
+This	O
+gene	O
+spans	O
+23	O
+kb	O
+and	O
+is	O
+composed	O
+of	O
+five	O
+exons	O
+and	O
+four	O
+introns	O
+.	O
+
+The	O
+remaining	O
+RAD	B-GENE
++	I-GENE
+cells	O
+progressed	O
+to	O
+form	O
+microcolonies	O
+(	O
+<	O
+30	O
+cells	O
+)	O
+containing	O
+aberrantly	O
+shaped	O
+inviable	O
+cells	O
+.	O
+
+The	O
+11	O
+;	O
+22	O
+chromosomal	O
+translocation	O
+specifically	O
+linked	O
+to	O
+Ewing	O
+sarcoma	O
+and	O
+primitive	O
+neuroectodermal	O
+tumor	O
+results	O
+in	O
+a	O
+chimeric	O
+molecule	O
+fusing	O
+the	O
+amino	O
+-	O
+terminal	O
+-	O
+encoding	O
+portion	O
+of	O
+the	O
+EWS	B-GENE
+gene	I-GENE
+to	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+DNA	O
+-	O
+binding	O
+domain	O
+encoded	O
+by	O
+the	O
+FLI1	B-GENE
+gene	I-GENE
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+a	O
+range	O
+of	O
+microenvironmental	O
+conditions	O
+exist	O
+within	O
+purified	O
+water	O
+systems	O
+,	O
+leading	O
+to	O
+variable	O
+populations	O
+of	O
+bacteria	O
+.	O
+
+X	O
+-	O
+linked	O
+liver	O
+glycogenosis	O
+:	O
+localization	O
+and	O
+isolation	O
+of	O
+a	O
+candidate	O
+gene	O
+.	O
+
+This	O
+conclusion	O
+is	O
+based	O
+on	O
+the	O
+observations	O
+of	O
+the	O
+immunologic	O
+changes	O
+that	O
+characterize	O
+the	O
+acute	O
+stages	O
+of	O
+illness	O
+as	O
+well	O
+as	O
+on	O
+the	O
+demonstrated	O
+association	O
+with	O
+toxin	O
+-	O
+producing	O
+bacteria	O
+in	O
+the	O
+pharynx	O
+and	O
+gastrointestinal	O
+tract	O
+.	O
+
+Measurement	O
+of	O
+anti	B-GENE
+-	I-GENE
+HCV	I-GENE
+IgM	I-GENE
+antibodies	I-GENE
+with	O
+an	O
+experimental	O
+kit	O
+
+Embryo	O
+coculture	O
+system	O
+may	O
+contribute	O
+to	O
+understand	O
+the	O
+mechanisms	O
+underlying	O
+the	O
+decrease	O
+of	O
+fertility	O
+with	O
+aging	O
+.	O
+
+These	O
+cell	O
+lines	O
+displayed	O
+methylation	O
+of	O
+the	O
+CpG	O
+island	O
+surrounding	O
+the	O
+first	O
+exon	O
+of	O
+p16INK4A	B-GENE
+and	O
+expressed	O
+abundant	O
+levels	O
+of	O
+a	O
+nontranslated	O
+mRNA	O
+containing	O
+an	O
+alternative	O
+first	O
+exon	O
+(	O
+E1	O
+beta	O
+)	O
+,	O
+as	O
+did	O
+all	O
+other	O
+cell	O
+lines	O
+in	O
+which	O
+the	O
+p16INK4A	B-GENE
+locus	I-GENE
+was	O
+not	O
+deleted	O
+.	O
+
+An	O
+immunoperoxidase	B-GENE
+reaction	O
+,	O
+PAP	B-GENE
+method	O
+,	O
+with	O
+the	O
+antiserum	O
+of	O
+Factor	B-GENE
+VIII	I-GENE
+as	O
+the	O
+primary	O
+antibody	O
+,	O
+was	O
+carried	O
+out	O
+in	O
+the	O
+endometrial	O
+biopsies	O
+to	O
+detect	O
+the	O
+Factor	B-GENE
+VIII	I-GENE
+activity	O
+in	O
+the	O
+endometrial	O
+endothelium	O
+before	O
+and	O
+after	O
+insertion	O
+of	O
+LNG	O
+-	O
+IUD	O
+-	O
+20	O
+.	O
+
+Egd1p	B-GENE
+is	O
+homologous	O
+to	O
+human	B-GENE
+BTF3b	I-GENE
+,	O
+recently	O
+identified	O
+as	O
+the	O
+beta	O
+subunit	O
+of	O
+the	O
+heterodimeric	B-GENE
+nascent	I-GENE
+-	I-GENE
+polypeptide	I-GENE
+-	I-GENE
+associated	I-GENE
+complex	I-GENE
+(	O
+NAC	B-GENE
+)	O
+involved	O
+in	O
+ensuring	O
+signal	O
+-	O
+sequence	O
+-	O
+specific	O
+protein	O
+sorting	O
+and	O
+translocation	O
+[	O
+Wiedmann	O
+et	O
+al	O
+.	O
+,	O
+Nature	O
+370	O
+(	O
+1994	O
+)	O
+434	O
+-	O
+440	O
+]	O
+.	O
+
+Purified	O
+PLB	B-GENE
+showed	O
+optimal	O
+lyase	B-GENE
+activity	O
+at	O
+pH	O
+10	O
+.	O
+0	O
+.	O
+
+The	O
+5	O
+'	O
+flanking	O
+regions	O
+of	O
+both	O
+pelA	B-GENE
+and	O
+pelB	B-GENE
+were	O
+translationally	O
+fused	O
+to	O
+the	O
+beta	B-GENE
+-	I-GENE
+glucuronidase	I-GENE
+gene	I-GENE
+and	O
+introduced	O
+into	O
+F	O
+.	O
+solani	O
+f	O
+.	O
+sp	O
+.	O
+pisi	O
+,	O
+and	O
+beta	B-GENE
+-	I-GENE
+glucuronidase	I-GENE
+activities	O
+of	O
+the	O
+transformants	O
+were	O
+measured	O
+.	O
+
+When	O
+nifA	B-GENE
+mRNA	I-GENE
+5	O
+'	O
+start	O
+points	O
+were	O
+mapped	O
+by	O
+primer	O
+extension	O
+,	O
+both	O
+a	O
+minor	O
+upstream	O
+transcript	O
+(	O
+s	O
+)	O
+starting	O
+45	O
+bp	O
+distal	O
+to	O
+the	O
+anaerobox	O
+and	O
+a	O
+major	O
+downstream	O
+transcript	O
+starting	O
+10	O
+bp	O
+distal	O
+to	O
+the	O
+sigma	B-GENE
+54	I-GENE
+box	O
+were	O
+observed	O
+.	O
+
+We	O
+failed	O
+to	O
+find	O
+these	O
+data	O
+to	O
+be	O
+useful	O
+in	O
+predicting	O
+the	O
+time	O
+of	O
+onset	O
+of	O
+initial	O
+seizures	O
+after	O
+acute	O
+ischemic	O
+stroke	O
+and	O
+recurrence	O
+.	O
+
+The	O
+human	B-GENE
+papillomavirus	I-GENE
+type	I-GENE
+16	I-GENE
+E7	I-GENE
+protein	I-GENE
+complements	O
+adenovirus	B-GENE
+type	I-GENE
+5	I-GENE
+E1A	I-GENE
+amino	O
+-	O
+terminus	O
+-	O
+dependent	O
+transactivation	O
+of	O
+adenovirus	B-GENE
+type	I-GENE
+5	I-GENE
+early	I-GENE
+genes	I-GENE
+and	O
+increases	O
+ATF	B-GENE
+and	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+DNA	O
+binding	O
+activity	O
+.	O
+
+A	O
+chaotropic	O
+detergent	O
+,	O
+0	O
+.	O
+1	O
+%	O
+Nonidet	O
+P	O
+-	O
+40	O
+,	O
+also	O
+abolished	O
+the	O
+interaction	O
+,	O
+further	O
+supporting	O
+the	O
+hydrophobic	O
+nature	O
+of	O
+the	O
+interaction	O
+.	O
+
+Degradation	O
+of	O
+the	O
+soybean	B-GENE
+ribulose	I-GENE
+-	I-GENE
+1	I-GENE
+,	I-GENE
+5	I-GENE
+-	I-GENE
+bisphosphate	I-GENE
+carboxylase	I-GENE
+small	I-GENE
+-	I-GENE
+subunit	I-GENE
+mRNA	I-GENE
+,	O
+SRS4	B-GENE
+,	O
+initiates	O
+with	O
+endonucleolytic	O
+cleavage	O
+.	O
+
+Cloning	O
+and	O
+sequencing	O
+revealed	O
+that	O
+dMax	B-GENE
+contains	O
+a	O
+deletion	O
+spanning	O
+the	O
+basic	O
+region	O
+and	O
+helix	O
+1	O
+and	O
+the	O
+loop	O
+of	O
+the	O
+helix	O
+-	O
+loop	O
+-	O
+helix	O
+region	O
+,	O
+presumably	O
+as	O
+a	O
+result	O
+of	O
+alternative	O
+splicing	O
+of	O
+max	B-GENE
+RNA	I-GENE
+.	O
+
+The	O
+domain	O
+structure	O
+of	O
+bovine	B-GENE
+LTBP	I-GENE
+-	I-GENE
+2	I-GENE
+is	O
+very	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+human	B-GENE
+LTBP	I-GENE
+-	I-GENE
+2	I-GENE
+,	O
+containing	O
+20	O
+examples	O
+of	O
+6	O
+-	O
+cysteine	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+like	I-GENE
+repeats	I-GENE
+,	O
+16	O
+of	O
+which	O
+have	O
+the	O
+consensus	O
+sequence	O
+for	O
+calcium	O
+binding	O
+,	O
+together	O
+with	O
+4	O
+examples	O
+of	O
+8	O
+-	O
+cysteine	O
+motifs	O
+characteristic	O
+of	O
+fibrillins	B-GENE
+and	O
+LTBP	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Similarly	O
+,	O
+expression	O
+of	O
+a	O
+transiently	O
+transfected	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+prothymosin	I-GENE
+alpha	I-GENE
+gene	I-GENE
+as	O
+the	O
+reporter	O
+was	O
+not	O
+affected	O
+by	O
+a	O
+repertoire	O
+of	O
+myc	B-GENE
+-	I-GENE
+derived	I-GENE
+genes	I-GENE
+,	O
+including	O
+myc	B-GENE
+itself	O
+and	O
+dominant	O
+or	O
+recessive	O
+negative	O
+myc	B-GENE
+mutants	I-GENE
+.	O
+
+Differential	O
+regulation	O
+of	O
+the	O
+alpha	B-GENE
+/	I-GENE
+beta	I-GENE
+interferon	I-GENE
+-	O
+stimulated	O
+Jak	B-GENE
+/	O
+Stat	B-GENE
+pathway	O
+by	O
+the	O
+SH2	B-GENE
+domain	O
+-	O
+containing	O
+tyrosine	B-GENE
+phosphatase	I-GENE
+SHPTP1	I-GENE
+.	O
+
+We	O
+now	O
+report	O
+the	O
+isolation	O
+and	O
+expression	O
+of	O
+cDNAs	O
+encoding	O
+PTF	B-GENE
+gamma	I-GENE
+and	O
+PTF	B-GENE
+delta	I-GENE
+,	O
+as	O
+well	O
+as	O
+functional	O
+studies	O
+with	O
+cognate	O
+antibodies	O
+that	O
+recognize	O
+the	O
+native	O
+PTF	B-GENE
+complex	I-GENE
+in	O
+HeLa	O
+extracts	O
+.	O
+
+Results	O
+from	O
+the	O
+mechanism	O
+study	O
+have	O
+revealed	O
+that	O
+YY1	B-GENE
+is	O
+able	O
+to	O
+inhibit	O
+transactivation	O
+mediated	O
+by	O
+either	O
+AP1	B-GENE
+or	O
+the	O
+Sp1	B-GENE
+-	I-GENE
+related	I-GENE
+protein	I-GENE
+,	O
+and	O
+YY1	B-GENE
+suppressive	O
+activity	O
+is	O
+DNA	O
+binding	O
+dependent	O
+.	O
+
+The	O
+skp1	B-GENE
++	I-GENE
+gene	I-GENE
+is	O
+not	O
+essential	O
+.	O
+
+The	O
+TEA1	B-GENE
+(	O
+Ty	B-GENE
+enhancer	I-GENE
+activator	I-GENE
+)	O
+gene	O
+sequence	O
+predicts	O
+a	O
+protein	O
+of	O
+86	O
+.	O
+9	O
+kDa	O
+whose	O
+N	O
+terminus	O
+contains	O
+a	O
+zinc	O
+cluster	O
+and	O
+dimerization	O
+motif	O
+typical	O
+of	O
+the	O
+Gal4	B-GENE
+-	I-GENE
+type	I-GENE
+family	I-GENE
+of	O
+DNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+Videonystagmoscopy	O
+has	O
+been	O
+used	O
+to	O
+subjectively	O
+observe	O
+the	O
+responses	O
+of	O
+the	O
+vestibular	O
+system	O
+in	O
+a	O
+population	O
+of	O
+patients	O
+with	O
+vestibular	O
+deficits	O
+.	O
+
+The	O
+MCA	O
+and	O
+UA	O
+PI	O
+values	O
+showed	O
+the	O
+greatest	O
+deviation	O
+for	O
+any	O
+single	O
+-	O
+vessel	O
+parameter	O
+.	O
+
+Stems	O
+contain	O
+distinctly	O
+less	O
+P	B-GENE
+protein	I-GENE
+mRNA	I-GENE
+and	O
+the	O
+relative	O
+level	O
+in	O
+roots	O
+is	O
+very	O
+low	O
+but	O
+still	O
+clearly	O
+detectable	O
+.	O
+
+The	O
+B	B-GENE
+.	I-GENE
+germanica	I-GENE
+cyclophilin	I-GENE
+amino	I-GENE
+acid	I-GENE
+sequence	I-GENE
+shares	O
+83	O
+%	O
+identity	O
+with	O
+the	O
+cytosolic	B-GENE
+cyclophilin	I-GENE
+isoform	I-GENE
+from	I-GENE
+Drosophila	I-GENE
+melanogaster	I-GENE
+(	O
+Cyp	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+The	O
+minimal	O
+region	O
+of	O
+overlap	O
+of	O
+Langer	O
+-	O
+Giedion	O
+syndrome	O
+deletions	O
+,	O
+previously	O
+identified	O
+by	O
+analysis	O
+of	O
+15	O
+patients	O
+,	O
+was	O
+placed	O
+on	O
+the	O
+map	O
+by	O
+analysis	O
+of	O
+2	O
+patients	O
+whose	O
+deletions	O
+define	O
+the	O
+endpoints	O
+.	O
+
+Comparison	O
+of	O
+promoters	O
+repressed	O
+by	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+reveals	O
+a	O
+weak	O
+consensus	O
+sequence	O
+of	O
+the	O
+initiator	O
+(	O
+Inr	O
+)	O
+element	O
+:	O
+TCA	O
+(	O
++	O
+1	O
+)	O
+YYYNY	O
+.	O
+
+The	O
+human	B-GENE
+gp39	I-GENE
+promoter	I-GENE
+.	O
+
+Transfection	O
+analyses	O
+indicate	O
+that	O
+mutation	O
+of	O
+any	O
+one	O
+of	O
+these	O
+TGACCT	O
+motifs	O
+or	O
+truncation	O
+of	O
+the	O
+entire	O
+HD	B-GENE
+PPRE	O
+into	O
+a	O
+separate	O
+DR1	O
+and	O
+DR2	O
+element	O
+significantly	O
+reduced	O
+the	O
+transcriptional	O
+response	O
+of	O
+HD	B-GENE
+PPRE	O
+to	O
+peroxisome	O
+proliferators	O
+.	O
+
+The	O
+site	O
+of	O
+autophosphorylation	O
+is	O
+Tyr397	O
+which	O
+corresponds	O
+to	O
+the	O
+consensus	O
+autophosphorylation	O
+site	O
+of	O
+other	O
+Src	B-GENE
+family	I-GENE
+tyrosine	B-GENE
+kinases	I-GENE
+.	O
+
+This	O
+protein	O
+-	O
+protein	O
+interaction	O
+does	O
+not	O
+require	O
+the	O
+simultaneous	O
+binding	O
+of	O
+Oct	B-GENE
+proteins	I-GENE
+to	O
+DNA	O
+,	O
+and	O
+high	O
+resolution	O
+footprinting	O
+of	O
+the	O
+Oct	B-GENE
+-	I-GENE
+DNA	I-GENE
+interaction	O
+reveals	O
+that	O
+binding	O
+of	O
+BOB	B-GENE
+.	I-GENE
+1	I-GENE
+/	O
+OBF	B-GENE
+.	I-GENE
+1	I-GENE
+to	O
+Oct1	B-GENE
+or	O
+Oct2	B-GENE
+does	O
+not	O
+alter	O
+the	O
+interaction	O
+with	O
+DNA	O
+.	O
+
+Together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+the	O
+TR2	B-GENE
+orphan	I-GENE
+receptor	I-GENE
+may	O
+be	O
+a	O
+master	O
+regulator	O
+in	O
+modulating	O
+the	O
+activation	O
+of	O
+two	O
+key	O
+HREs	O
+,	O
+RARE	O
+beta	O
+and	O
+CRBPIIp	O
+,	O
+involved	O
+in	O
+the	O
+retinoic	O
+acid	O
+signal	O
+transduction	O
+pathway	O
+.	O
+
+Using	O
+a	O
+series	O
+of	O
+mutant	O
+proteins	O
+,	O
+we	O
+have	O
+characterized	O
+domains	O
+responsible	O
+for	O
+activation	O
+or	O
+repression	O
+.	O
+
+It	O
+is	O
+considered	O
+that	O
+the	O
+recurrent	O
+annular	O
+erythema	O
+is	O
+a	O
+specific	O
+skin	O
+manifestation	O
+of	O
+SjS	O
+with	O
+anti	B-GENE
+SS	I-GENE
+-	I-GENE
+A	I-GENE
+/	O
+SS	B-GENE
+-	I-GENE
+B	I-GENE
+antibodies	I-GENE
+.	O
+
+Competition	O
+needs	O
+to	O
+be	O
+better	O
+studied	O
+,	O
+since	O
+in	O
+Central	O
+America	O
+and	O
+Caribean	O
+islands	O
+this	O
+kind	O
+of	O
+study	O
+has	O
+favored	O
+the	O
+biological	O
+control	O
+of	O
+planorbid	O
+species	O
+.	O
+
+In	O
+this	O
+paper	O
+we	O
+describe	O
+properties	O
+of	O
+the	O
+cdc10	B-GENE
+-	O
+C4	O
+mutant	O
+of	O
+the	O
+fission	O
+yeast	O
+Schizosaccharomyces	O
+pombe	O
+.	O
+
+TIEG	B-GENE
+expression	O
+in	O
+hFOB	O
+cells	O
+was	O
+highly	O
+induced	O
+by	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+and	O
+bone	B-GENE
+morphogenetic	I-GENE
+protein	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+BMP	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+,	O
+with	O
+a	O
+moderate	O
+induction	O
+by	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+EGF	B-GENE
+)	O
+,	O
+but	O
+no	O
+induction	O
+by	O
+other	O
+growth	O
+factors	O
+/	O
+cytokines	O
+was	O
+observed	O
+.	O
+
+The	O
+predicted	O
+protein	O
+products	O
+of	O
+ORFs	B-GENE
+N2417	I-GENE
+and	O
+N2403	B-GENE
+present	O
+similarities	O
+with	O
+domains	O
+from	O
+proteins	O
+of	O
+other	O
+organisms	O
+:	O
+the	O
+Candida	O
+maltosa	O
+cycloheximide	B-GENE
+-	I-GENE
+resistance	I-GENE
+protein	I-GENE
+,	O
+the	O
+human	O
+interleukin	B-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+factor	I-GENE
+(	O
+ILF	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+highly	O
+expressed	O
+ADH1	B-GENE
+gene	I-GENE
+is	O
+represented	O
+in	O
+this	O
+database	O
+by	O
+no	O
+less	O
+than	O
+20	O
+EST	O
+sequences	O
+.	O
+
+Five	O
+families	O
+of	O
+Ashkenazi	O
+Jewish	O
+descent	O
+carried	O
+the	O
+185delAG	O
+mutation	O
+and	O
+shared	O
+the	O
+same	O
+haplotype	O
+at	O
+eight	O
+polymorphic	O
+markers	O
+spanning	O
+approximately	O
+850	O
+kb	O
+at	O
+BRCA1	B-GENE
+.	O
+
+The	O
+subjects	O
+from	O
+the	O
+two	O
+regions	O
+with	O
+a	O
+higher	O
+pollution	O
+level	O
+had	O
+lower	O
+FVC	O
+and	O
+FEV1	O
+values	O
+than	O
+those	O
+from	O
+the	O
+Viskovo	O
+region	O
+.	O
+
+PTP	B-GENE
+-	I-GENE
+S3	I-GENE
+differs	O
+from	O
+PTP	B-GENE
+-	I-GENE
+S4	I-GENE
+in	O
+having	O
+a	O
+deletion	O
+of	O
+19	O
+amino	O
+acids	O
+corresponding	O
+to	O
+exon	O
+E1	O
+.	O
+
+When	O
+differentiated	O
+G0	O
+-	O
+arrested	O
+leaf	O
+cells	O
+were	O
+induced	O
+to	O
+resume	O
+cell	O
+division	O
+by	O
+treatment	O
+with	O
+plant	O
+hormones	O
+,	O
+cycMs4	B-GENE
+transcription	O
+was	O
+induced	O
+before	O
+the	O
+onset	O
+of	O
+DNA	O
+synthesis	O
+.	O
+
+A	O
+survey	O
+is	O
+given	O
+of	O
+the	O
+pharmacological	O
+backgrounds	O
+that	O
+are	O
+relevant	O
+for	O
+the	O
+drug	O
+treatment	O
+of	O
+essential	O
+hypertension	O
+in	O
+the	O
+elderly	O
+.	O
+
+Protein	O
+kinases	O
+play	O
+pivotal	O
+roles	O
+in	O
+the	O
+control	O
+of	O
+many	O
+cellular	O
+processes	O
+.	O
+
+Interestingly	O
+,	O
+internal	O
+and	O
+5	O
+'	O
+deletions	O
+revealed	O
+tha	O
+the	O
+distal	O
+promoter	O
+was	O
+not	O
+required	O
+for	O
+full	O
+transcriptional	O
+activity	O
+and	O
+that	O
+the	O
+first	O
+631	O
+base	O
+pairs	O
+of	O
+WNT	B-GENE
+-	I-GENE
+5A	I-GENE
+harbored	O
+the	O
+strongest	O
+promoter	O
+activity	O
+.	O
+
+The	O
+protein	O
+kinase	O
+domains	O
+of	O
+LIMK1	B-GENE
+and	O
+LIMK2	B-GENE
+are	O
+unique	O
+in	O
+that	O
+they	O
+contain	O
+an	O
+unusual	O
+sequence	O
+motif	O
+Asp	O
+-	O
+Leu	O
+-	O
+Asn	O
+-	O
+Ser	O
+-	O
+His	O
+-	O
+Asn	O
+in	O
+subdomain	O
+VIB	O
+and	O
+a	O
+highly	O
+basic	O
+insert	O
+between	O
+subdomains	O
+VII	O
+and	O
+VIII	O
+.	O
+
+A	O
+human	O
+recombinant	O
+cDNA	O
+clone	O
+that	O
+encoded	O
+253	O
+amino	O
+acids	O
+residues	O
+of	O
+a	O
+zinc	B-GENE
+-	I-GENE
+finger	I-GENE
+protein	I-GENE
+(	O
+THZif	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+was	O
+cloned	O
+by	O
+screening	O
+a	O
+cDNA	O
+library	O
+prepared	O
+from	O
+human	O
+promyelocytic	O
+leukemia	O
+HL60	O
+cells	O
+with	O
+synthetic	O
+oligodeoxynucleotide	O
+probes	O
+that	O
+corresponded	O
+to	O
+the	O
+amino	O
+acid	O
+sequences	O
+of	O
+tryptic	O
+peptides	O
+derived	O
+from	O
+the	O
+DNA	O
+-	O
+binding	O
+protein	O
+specific	O
+for	O
+the	O
+nuclease	B-GENE
+-	I-GENE
+hypersensitive	I-GENE
+element	I-GENE
+(	O
+NHE	B-GENE
+)	O
+of	O
+the	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+.	O
+
+Erythrocyte	O
+AA	O
+in	O
+FO	O
++	O
+EPO	B-GENE
+-	O
+supplemented	O
+infants	O
+remained	O
+low	O
+and	O
+below	O
+breast	O
+-	O
+and	O
+placebo	O
+formula	O
+-	O
+fed	O
+levels	O
+.	O
+
+Taking	O
+into	O
+consideration	O
+weight	O
+and	O
+seasonal	O
+changes	O
+in	O
+bone	O
+mass	O
+,	O
+total	O
+(	O
+TBBMC	O
+)	O
+and	O
+regional	O
+body	O
+bone	O
+mineral	O
+content	O
+were	O
+measured	O
+in	O
+38	O
+women	O
+treated	O
+with	O
+GnRH	B-GENE
+agonists	O
+for	O
+6	O
+months	O
+for	O
+endometriosis	O
+or	O
+leiomyomata	O
+.	O
+
+The	O
+encoded	O
+polypeptide	O
+is	O
+similar	O
+in	O
+sequence	O
+to	O
+the	O
+ABA	B-GENE
+-	I-GENE
+1	I-GENE
+allergen	I-GENE
+of	I-GENE
+Ascaris	I-GENE
+,	O
+the	O
+gp15	B-GENE
+/	I-GENE
+400	I-GENE
+'	I-GENE
+ladder	I-GENE
+'	I-GENE
+protein	I-GENE
+of	I-GENE
+Brugia	I-GENE
+malayi	I-GENE
+,	I-GENE
+Brugia	I-GENE
+pahangi	I-GENE
+and	I-GENE
+Wuchereria	I-GENE
+bancrofti	I-GENE
+,	O
+and	O
+a	O
+15	B-GENE
+-	I-GENE
+kDa	I-GENE
+antigen	I-GENE
+of	I-GENE
+Dirofilaria	I-GENE
+immitis	I-GENE
+.	O
+
+Spontaneous	O
+recovery	O
+occurs	O
+within	O
+30	O
+min	O
+to	O
+2	O
+hrs	O
+.	O
+
+DAF	B-GENE
+is	O
+a	O
+70	O
+kD	O
+glycoprotein	O
+containing	O
+complement	O
+regulatory	O
+short	O
+consensus	O
+repeats	O
+(	O
+SCRs	O
+)	O
+;	O
+its	O
+gene	O
+is	O
+located	O
+in	O
+the	O
+regulation	B-GENE
+of	I-GENE
+complement	I-GENE
+activation	I-GENE
+(	O
+RCA	B-GENE
+)	O
+gene	O
+cluster	O
+on	O
+chromosome	O
+1	O
+and	O
+is	O
+about	O
+40	O
+kb	O
+in	O
+size	O
+.	O
+
+There	O
+is	O
+no	O
+TATA	O
+box	O
+around	O
+the	O
+transcriptional	O
+start	O
+points	O
+(	O
+tsp	O
+)	O
+,	O
+as	O
+determined	O
+by	O
+primer	O
+extension	O
+analysis	O
+.	O
+
+According	O
+to	O
+the	O
+investigation	O
+,	O
+the	O
+recent	O
+burst	O
+of	O
+pseudoterranovosis	O
+in	O
+this	O
+area	O
+can	O
+be	O
+attributed	O
+to	O
+the	O
+increased	O
+presence	O
+of	O
+sea	O
+lions	O
+,	O
+which	O
+proliferate	O
+in	O
+the	O
+Arctic	O
+region	O
+,	O
+then	O
+migrate	O
+to	O
+the	O
+northern	O
+Japan	O
+Sea	O
+and	O
+eat	O
+the	O
+intermediate	O
+host	O
+fish	O
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+efficacies	O
+of	O
+adjuvant	O
+carboplatin	O
+and	O
+of	O
+abdominal	O
+radiotherapy	O
+seem	O
+to	O
+be	O
+identical	O
+.	O
+
+To	O
+identify	O
+some	O
+of	O
+the	O
+genes	O
+expressed	O
+in	O
+LPS	O
+-	O
+activated	O
+coelomocytes	O
+,	O
+we	O
+sequenced	O
+randomly	O
+chosen	O
+clones	O
+from	O
+a	O
+directionally	O
+constructed	O
+cDNA	O
+library	O
+to	O
+produce	O
+a	O
+set	O
+of	O
+expressed	O
+sequence	O
+tags	O
+(	O
+ESTs	O
+)	O
+.	O
+
+Characterization	O
+of	O
+an	O
+EcR	B-GENE
+/	O
+USP	B-GENE
+heterodimer	O
+target	O
+site	O
+that	O
+mediates	O
+ecdysone	O
+responsiveness	O
+of	O
+the	O
+Drosophila	B-GENE
+Lsp	I-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+.	O
+
+Thus	O
+,	O
+SPECT	O
+was	O
+not	O
+as	O
+sensitive	O
+as	O
+PET	O
+in	O
+this	O
+activation	O
+task	O
+.	O
+
+Transcriptional	O
+activation	O
+of	O
+the	O
+chicken	B-GENE
+lysozyme	I-GENE
+gene	I-GENE
+by	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+Bp65	I-GENE
+(	O
+RelA	B-GENE
+)	O
+and	O
+c	B-GENE
+-	I-GENE
+Rel	I-GENE
+,	O
+but	O
+not	O
+by	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+Bp50	I-GENE
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+the	O
+bradycardic	O
+agents	O
+alinidine	O
+and	O
+zatebradine	O
+do	O
+not	O
+exert	O
+antiarrhythmic	O
+efficacy	O
+against	O
+SVT	O
+induced	O
+during	O
+subacute	O
+myocardial	O
+infarction	O
+in	O
+conscious	O
+dogs	O
+.	O
+
+In	O
+vivo	O
+,	O
+selective	O
+activation	O
+of	O
+SAPKs	B-GENE
+stimulates	O
+formation	O
+of	O
+the	O
+ternary	O
+complex	O
+containing	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+and	O
+the	O
+serum	O
+response	O
+element	O
+,	O
+and	O
+enhances	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+dependent	O
+transcription	O
+.	O
+
+An	O
+epidemic	O
+of	O
+hepatitis	O
+B	O
+virus	O
+infection	O
+among	O
+intravenous	O
+drug	O
+users	O
+in	O
+Iceland	O
+.	O
+
+Three	O
+of	O
+these	O
+subunits	O
+are	O
+also	O
+homologous	O
+to	O
+the	O
+dimeric	O
+POR	B-GENE
+from	O
+a	O
+mesophilic	O
+archaeon	O
+,	O
+Halobacterium	O
+halobium	O
+(	O
+21	O
+%	O
+identity	O
+)	O
+.	O
+
+The	O
+transposon	O
+-	O
+inactivated	O
+gene	O
+,	O
+designated	O
+pilP	B-GENE
+,	O
+is	O
+525	O
+bp	O
+long	O
+,	O
+potentially	O
+encoding	O
+a	O
+19	O
+.	O
+1	O
+-	O
+kDa	O
+protein	O
+precursor	O
+that	O
+contains	O
+a	O
+typical	O
+membrane	O
+lipoprotein	O
+leader	O
+sequence	O
+.	O
+
+Cheung	O
+and	O
+S	O
+.	O
+
+Upstream	O
+of	O
+the	O
+dra	B-GENE
+gene	I-GENE
+an	O
+open	O
+reading	O
+frame	O
+of	O
+313	O
+amino	O
+acids	O
+was	O
+identified	O
+.	O
+
+Sucrose	O
+-	O
+specific	O
+regulation	O
+of	O
+scrB	B-GENE
+was	O
+also	O
+lost	O
+upon	O
+deletion	O
+of	O
+4	O
+bp	O
+of	O
+a	O
+palindromic	O
+sequence	O
+(	O
+OB	O
+)	O
+covering	O
+positions	O
++	O
+6	O
+to	O
++	O
+21	O
+downstream	O
+of	O
+the	O
+scrB	B-GENE
+transcriptional	O
+start	O
+site	O
+.	O
+
+In	O
+E	O
+.	O
+coli	O
+,	O
+CheW	B-GENE
+mediates	O
+the	O
+physical	O
+coupling	O
+of	O
+the	O
+receptors	O
+to	O
+the	O
+kinase	O
+CheA	B-GENE
+.	O
+
+The	O
+promoter	O
+of	O
+the	O
+first	O
+gene	O
+,	O
+epiF	B-GENE
+,	O
+responded	O
+to	O
+the	O
+activator	B-GENE
+protein	I-GENE
+EpiQ	I-GENE
+and	O
+contained	O
+a	O
+palindromic	O
+sequence	O
+similar	O
+to	O
+the	O
+EpiQ	B-GENE
+binding	I-GENE
+site	I-GENE
+of	O
+the	O
+epiA	B-GENE
+promoter	I-GENE
+,	O
+which	O
+is	O
+also	O
+activated	O
+by	O
+EpiQ	B-GENE
+.	O
+
+CXC	O
+chemokines	O
+bind	O
+to	O
+unique	O
+sets	O
+of	O
+selectivity	O
+determinants	O
+that	O
+can	O
+function	O
+independently	O
+and	O
+are	O
+broadly	O
+distributed	O
+on	O
+multiple	O
+domains	O
+of	O
+human	O
+interleukin	B-GENE
+-	I-GENE
+8	I-GENE
+receptor	I-GENE
+B	I-GENE
+.	O
+
+Oligodeoxynucleotides	O
+antisense	O
+to	O
+the	O
+predicted	O
+translation	O
+initiation	O
+regions	O
+of	O
+ICP4	B-GENE
+and	O
+pp38	B-GENE
+mRNAs	I-GENE
+inhibited	O
+proliferation	O
+of	O
+MSB1	O
+cells	O
+but	O
+not	O
+MDCC	O
+-	O
+CU91	O
+(	O
+CU91	O
+)	O
+reticuloendotheliosis	O
+virus	O
+-	O
+transformed	O
+cells	O
+.	O
+
+Retroviral	O
+replication	O
+requires	O
+that	O
+a	O
+portion	O
+of	O
+the	O
+primary	O
+transcripts	O
+generated	O
+from	O
+proviral	O
+DNA	O
+be	O
+spliced	O
+to	O
+serve	O
+as	O
+mRNA	O
+for	O
+the	O
+envelope	B-GENE
+protein	I-GENE
+and	O
+in	O
+Rous	O
+sarcoma	O
+virus	O
+as	O
+src	B-GENE
+mRNA	I-GENE
+.	O
+
+In	O
+this	O
+case	O
+the	O
+degree	O
+of	O
+promoter	O
+methylation	O
+,	O
+which	O
+could	O
+extend	O
+beyond	O
+the	O
+T	O
+-	O
+DNA	O
+borders	O
+,	O
+was	O
+not	O
+correlated	O
+with	O
+the	O
+reduction	O
+in	O
+steady	O
+-	O
+state	O
+poly	O
+(	O
+A	O
+)	O
++	O
+mRNA	O
+levels	O
+,	O
+the	O
+silenced	O
+state	O
+was	O
+transmitted	O
+through	O
+meiosis	O
+and	O
+reactivation	O
+lasted	O
+several	O
+generations	O
+.	O
+
+Thus	O
+,	O
+the	O
+consensus	O
+sequences	O
+for	O
+phosphatase	O
+regulation	O
+are	O
+5	O
+'	O
+-	O
+GCACGTGGG	O
+-	O
+3	O
+'	O
+and	O
+5	O
+'	O
+-	O
+GCACGTTTT	O
+-	O
+3	O
+'	O
+which	O
+differ	O
+from	O
+the	O
+binding	O
+sequences	O
+for	O
+the	O
+Cpflp	B-GENE
+protein	O
+required	O
+for	O
+transcription	O
+of	O
+the	O
+genes	O
+in	O
+methionine	O
+biosynthesis	O
+and	O
+for	O
+centromere	O
+function	O
+.	O
+
+Here	O
+we	O
+report	O
+that	O
+the	O
+proline	O
+-	O
+rich	O
+region	O
+of	O
+CAP	B-GENE
+is	O
+recognized	O
+by	O
+the	O
+SH3	B-GENE
+domains	I-GENE
+of	O
+several	O
+proteins	O
+,	O
+including	O
+the	O
+yeast	B-GENE
+actin	I-GENE
+-	I-GENE
+associated	I-GENE
+protein	I-GENE
+Abp1p	I-GENE
+.	O
+
+We	O
+have	O
+identified	O
+and	O
+characterized	O
+a	O
+vitamin	O
+D	O
+response	O
+element	O
+(	O
+VDRE	O
+)	O
+in	O
+the	O
+promoter	O
+of	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+.	O
+
+In	O
+addition	O
+to	O
+protein	O
+binding	O
+at	O
+sequences	O
+known	O
+to	O
+be	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+transcription	O
+,	O
+genomic	O
+footprinting	O
+of	O
+the	O
+entire	O
+promoter	O
+region	O
+also	O
+showed	O
+that	O
+a	O
+protein	O
+factor	O
+is	O
+constitutively	O
+bound	O
+to	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+rep3	B-GENE
+gene	I-GENE
+.	O
+
+Differentiation	O
+was	O
+not	O
+observed	O
+after	O
+cellular	O
+expression	O
+of	O
+GTPase	B-GENE
+-	O
+deficient	O
+forms	O
+of	O
+alpha	B-GENE
+i2	I-GENE
+or	O
+alpha	B-GENE
+0	I-GENE
+,	O
+indicating	O
+selectivity	O
+for	O
+the	O
+Gq	B-GENE
+family	I-GENE
+of	O
+G	B-GENE
+proteins	I-GENE
+.	O
+
+Consistent	O
+with	O
+a	O
+possible	O
+role	O
+in	O
+transcription	O
+,	O
+Paf1p	B-GENE
+is	O
+localized	O
+to	O
+the	O
+nucleus	O
+.	O
+
+By	O
+comparing	O
+the	O
+abundances	O
+of	O
+many	O
+yeast	O
+transcripts	O
+in	O
+isogenic	O
+wild	O
+-	O
+type	O
+and	O
+paf1	B-GENE
+mutant	I-GENE
+strains	O
+,	O
+we	O
+have	O
+identified	O
+genes	O
+whose	O
+expression	O
+is	O
+affected	O
+by	O
+PAF1	B-GENE
+.	O
+
+Paf1p	B-GENE
+may	O
+therefore	O
+be	O
+required	O
+for	O
+both	O
+positive	O
+and	O
+negative	O
+regulation	O
+of	O
+subsets	O
+of	O
+yeast	O
+genes	O
+.	O
+
+Using	O
+a	O
+high	O
+-	O
+copy	O
+suppression	O
+strategy	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+yeast	O
+gene	O
+(	O
+UBS1	B-GENE
+)	O
+whose	O
+elevated	O
+expression	O
+suppresses	O
+the	O
+conditional	O
+cell	O
+cycle	O
+defects	O
+associated	O
+with	O
+cdc34	B-GENE
+mutations	O
+.	O
+
+Molecular	O
+characterization	O
+of	O
+malignant	O
+melanoma	O
+of	O
+soft	O
+parts	O
+or	O
+soft	O
+tissue	O
+clear	O
+cell	O
+sarcoma	O
+which	O
+shares	O
+t	O
+(	O
+12	O
+;	O
+22	O
+)	O
+chromosome	O
+translocation	O
+revealed	O
+fusion	O
+of	O
+EWS	B-GENE
+with	O
+a	O
+transcriptional	O
+factor	O
+gene	B-GENE
+ATF	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Clones	O
+that	O
+expressed	O
+DBD	O
+exhibited	O
+a	O
+dominant	O
+negative	O
+phenotype	O
+and	O
+did	O
+not	O
+elicit	O
+antiviral	O
+activity	O
+against	O
+vesicular	O
+stomatitis	O
+virus	O
+(	O
+VSV	O
+)	O
+infection	O
+upon	O
+IFN	B-GENE
+treatment	O
+.	O
+
+Abp1	B-GENE
+preferentially	O
+binds	O
+to	O
+multiple	O
+sites	O
+in	O
+ARS	B-GENE
+3002	I-GENE
+and	O
+to	O
+the	O
+DNA	O
+polymer	O
+poly	O
+[	O
+d	O
+(	O
+A	O
+.	O
+T	O
+)	O
+]	O
+.	O
+
+Identification	O
+,	O
+purification	O
+,	O
+and	O
+molecular	O
+cloning	O
+of	O
+autonomously	B-GENE
+replicating	I-GENE
+sequence	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+from	I-GENE
+fission	I-GENE
+yeast	I-GENE
+Schizosaccharomyces	I-GENE
+pombe	I-GENE
+.	O
+
+A	O
+short	O
+open	O
+reading	O
+frame	O
+(	O
+ORF2	O
+)	O
+,	O
+of	O
+unknown	O
+function	O
+,	O
+is	O
+present	O
+in	O
+all	O
+FIV	O
+isolates	O
+.	O
+
+The	O
+patient	O
+was	O
+homozygous	O
+for	O
+the	O
+underlying	O
+mutation	O
+,	O
+which	O
+was	O
+found	O
+to	O
+be	O
+a	O
+G	O
+-	O
+-	O
+>	O
+T	O
+transversion	O
+within	O
+the	O
+acceptor	O
+splice	O
+site	O
+between	O
+intron	O
+e	O
+and	O
+exon	O
+6	O
+,	O
+abolishing	O
+normal	O
+RNA	O
+splicing	O
+.	O
+
+These	O
+regions	O
+overlap	O
+with	O
+the	O
+HIT	B-GENE
+protein	I-GENE
+similarity	I-GENE
+regions	I-GENE
+.	O
+
+We	O
+tested	O
+10	O
+rats	O
+with	O
+electrophysiologically	O
+guided	O
+,	O
+ibotenic	O
+acid	O
+lesions	O
+of	O
+the	O
+PBN	O
+(	O
+PBNx	O
+)	O
+to	O
+determine	O
+whether	O
+they	O
+could	O
+acquire	O
+a	O
+LiCl	O
+-	O
+induced	O
+CTA	O
+to	O
+l	O
+-	O
+alanine	O
+(	O
+0	O
+.	O
+3	O
+M	O
+)	O
+or	O
+demonstrate	O
+a	O
+sodium	O
+appetite	O
+following	O
+furosemide	O
+treatment	O
+and	O
+overnight	O
+access	O
+to	O
+sodium	O
+deficient	O
+chow	O
+.	O
+
+Liposomal	O
+Amphotericin	O
+-	O
+B	O
+failed	O
+in	O
+6	O
+/	O
+7	O
+patients	O
+with	O
+culture	O
+-	O
+proven	O
+mycosis	O
+who	O
+died	O
+from	O
+infection	O
+with	O
+Aspergillus	O
+(	O
+n	O
+=	O
+2	O
+)	O
+and	O
+Candida	O
+(	O
+n	O
+=	O
+4	O
+)	O
+,	O
+respectively	O
+.	O
+
+Mg2	O
++	O
+and	O
+Mn2	O
++	O
+compete	O
+for	O
+binding	O
+sites	O
+,	O
+with	O
+the	O
+former	O
+having	O
+lower	O
+affinity	O
+.	O
+
+Magnetic	O
+storm	O
+indicators	O
+could	O
+be	O
+used	O
+in	O
+medicine	O
+,	O
+in	O
+geophysics	O
+and	O
+for	O
+special	O
+purposes	O
+.	O
+
+Transgenic	O
+tobacco	O
+plants	O
+(	O
+ppa	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+constitutively	O
+expressing	O
+Escherichia	B-GENE
+coli	I-GENE
+pyrophosphatase	I-GENE
+behind	O
+the	O
+35S	B-GENE
+CaMV	I-GENE
+promoter	I-GENE
+accumulate	O
+high	O
+levels	O
+of	O
+soluble	O
+sugars	O
+in	O
+their	O
+leaves	O
+[	O
+27	O
+]	O
+.	O
+
+Hb	B-GENE
+levels	O
+remained	O
+adequate	O
+(	O
+Hb	B-GENE
+=	O
+10	O
+.	O
+68	O
++	O
+/	O
+-	O
+0	O
+.	O
+77	O
+g	O
+/	O
+dl	O
+)	O
+after	O
+14	O
+.	O
+6	O
++	O
+/	O
+-	O
+7	O
+.	O
+64	O
+months	O
+.	O
+
+CBT	O
+is	O
+discussed	O
+in	O
+comparison	O
+with	O
+the	O
+Wisconsin	O
+Card	O
+Sorting	O
+Test	O
+as	O
+a	O
+potential	O
+cognitive	O
+activation	O
+task	O
+for	O
+functional	O
+neuroimaging	O
+of	O
+the	O
+frontal	O
+lobes	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+although	O
+218leu	O
+retains	O
+normal	O
+transactivation	O
+activity	O
+on	O
+a	O
+p53	B-GENE
+promoter	I-GENE
+in	O
+yeast	O
+at	O
+physiological	O
+temperatures	O
+,	O
+it	O
+is	O
+not	O
+capable	O
+of	O
+normal	O
+p53	B-GENE
+function	O
+in	O
+the	O
+presence	O
+of	O
+a	O
+248trp	B-GENE
+allele	I-GENE
+in	O
+SNU	O
+-	O
+C5	O
+cells	O
+.	O
+
+Neither	O
+class	O
+II	O
+nor	O
+IV	O
+infections	O
+precluded	O
+transplantation	O
+.	O
+
+Although	O
+a	O
+great	O
+deal	O
+is	O
+understood	O
+about	O
+how	O
+bHLH	B-GENE
+factors	I-GENE
+activate	O
+gene	O
+transcription	O
+via	O
+E	O
+-	O
+box	O
+DNA	O
+consensus	O
+sequences	O
+,	O
+studies	O
+of	O
+bHLH	B-GENE
+factor	I-GENE
+function	O
+in	O
+higher	O
+eukaryotes	O
+often	O
+have	O
+been	O
+hindered	O
+by	O
+the	O
+presence	O
+of	O
+multiple	O
+family	O
+members	O
+.	O
+
+Mobility	O
+and	O
+supershift	O
+assays	O
+demonstrated	O
+that	O
+upstream	B-GENE
+stimulatory	I-GENE
+factor	I-GENE
+(	O
+USF	B-GENE
+)	O
+and	O
+Sp1	B-GENE
+bind	O
+to	O
+the	O
+former	O
+elements	O
+and	O
+competition	O
+experiments	O
+confirmed	O
+that	O
+CREB	B-GENE
+/	O
+ATF	B-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+bind	O
+to	O
+the	O
+CRE	O
+/	O
+TRE	O
+element	O
+.	O
+
+In	O
+these	O
+cases	O
+,	O
+greatly	O
+increased	O
+human	B-GENE
+chorionic	I-GENE
+gonadotropin	I-GENE
+(	O
+hCG	B-GENE
+)	O
+levels	O
+and	O
+suppressed	O
+TSH	B-GENE
+levels	O
+suggest	O
+that	O
+hCG	B-GENE
+has	O
+thyrotropic	O
+activity	O
+.	O
+
+High	O
+fibrinogen	B-GENE
+levels	O
+could	O
+thus	O
+be	O
+a	O
+risk	O
+for	O
+perioperative	O
+thrombosis	O
+.	O
+
+Strontium	O
+chloride	O
+Sr	O
+89	O
+is	O
+costly	O
+,	O
+but	O
+preliminary	O
+analysis	O
+indicates	O
+that	O
+it	O
+may	O
+reduce	O
+management	O
+expenditures	O
+overall	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+We	O
+propose	O
+that	O
+epigenetic	O
+features	O
+of	O
+tissue	O
+-	O
+specific	O
+control	O
+and	O
+of	O
+the	O
+control	O
+of	O
+allelic	O
+expression	O
+are	O
+intricately	O
+linked	O
+.	O
+
+This	O
+study	O
+determined	O
+the	O
+arthritogenic	O
+potential	O
+of	O
+silicone	O
+gel	O
+by	O
+either	O
+mixing	O
+it	O
+with	O
+bovine	B-GENE
+collagen	I-GENE
+II	I-GENE
+(	O
+BII	B-GENE
+)	O
+or	O
+by	O
+injecting	O
+silicone	O
+gel	O
+alone	O
+in	O
+DA	O
+rats	O
+.	O
+
+This	O
+5	O
+'	O
+splice	O
+site	O
+sequence	O
+was	O
+required	O
+for	O
+enhanced	O
+polyadenylation	O
+and	O
+was	O
+recognized	O
+by	O
+both	O
+U1	B-GENE
+small	I-GENE
+nuclear	I-GENE
+ribonucleoproteins	I-GENE
+(	O
+snRNPs	O
+)	O
+and	O
+alternative	B-GENE
+splicing	I-GENE
+factor	I-GENE
+/	O
+splicing	B-GENE
+factor	I-GENE
+2	I-GENE
+(	O
+ASF	B-GENE
+/	O
+SF2	B-GENE
+)	O
+.	O
+
+This	O
+analysis	O
+revealed	O
+that	O
+SAP	B-GENE
+145	I-GENE
+,	O
+together	O
+with	O
+four	O
+other	O
+SF3a	B-GENE
+/	O
+SF3b	B-GENE
+subunits	O
+,	O
+UV	O
+cross	O
+-	O
+links	O
+to	O
+pre	O
+-	O
+mRNA	O
+in	O
+a	O
+20	O
+-	O
+nucleotide	O
+region	O
+upstream	O
+of	O
+the	O
+BPS	O
+.	O
+
+Although	O
+the	O
+consumption	O
+of	O
+myoglobin	B-GENE
+-	O
+bound	O
+O2	O
+(	O
+MbO2	O
+)	O
+stores	O
+in	O
+seal	O
+muscles	O
+has	O
+been	O
+demonstrated	O
+in	O
+seal	O
+muscles	O
+during	O
+laboratory	O
+simulations	O
+of	O
+diving	O
+,	O
+this	O
+may	O
+not	O
+be	O
+a	O
+feature	O
+of	O
+normal	O
+field	O
+diving	O
+in	O
+which	O
+measurements	O
+of	O
+heart	O
+rate	O
+and	O
+lactate	O
+production	O
+show	O
+marked	O
+differences	O
+from	O
+the	O
+profound	O
+diving	O
+response	O
+induced	O
+by	O
+forced	O
+immersion	O
+.	O
+
+The	O
+human	B-GENE
+purH	I-GENE
+cDNA	I-GENE
+is	O
+1776	O
+base	O
+pairs	O
+in	O
+length	O
+encoding	O
+for	O
+a	O
+591	O
+-	O
+amino	O
+acid	O
+polypeptic	O
+(	O
+Mr	O
+=	O
+64	O
+,	O
+425	O
+)	O
+.	O
+
+The	O
+Saccharomyces	O
+cerevisiae	O
+spindle	O
+pole	O
+body	O
+duplication	O
+gene	B-GENE
+MPS1	I-GENE
+is	O
+part	O
+of	O
+a	O
+mitotic	O
+checkpoint	O
+.	O
+
+In	O
+our	O
+opinion	O
+,	O
+the	O
+SM	O
+-	O
+CMA	O
+system	O
+is	O
+,	O
+despite	O
+some	O
+shortcomings	O
+in	O
+its	O
+user	O
+-	O
+interface	O
+,	O
+a	O
+useful	O
+and	O
+versatile	O
+instrument	O
+for	O
+examination	O
+of	O
+human	O
+semen	O
+samples	O
+,	O
+with	O
+desirable	O
+features	O
+.	O
+
+Oligonucleotides	O
+,	O
+designed	O
+on	O
+the	O
+basis	O
+of	O
+conserved	O
+flanking	O
+amino	O
+acid	O
+sequence	O
+segments	O
+within	O
+the	O
+catalytic	O
+domain	O
+of	O
+eukaryotic	B-GENE
+protein	I-GENE
+kinase	I-GENE
+C	I-GENE
+(	O
+PKC	B-GENE
+)	O
+proteins	O
+,	O
+were	O
+used	O
+as	O
+primers	O
+for	O
+polymerase	O
+chain	O
+reactions	O
+to	O
+amplify	O
+a	O
+427	O
+-	O
+bp	O
+chromosomal	O
+DNA	O
+fragment	O
+from	O
+the	O
+filamentous	O
+fungus	O
+Trichoderma	O
+reesei	O
+.	O
+
+Disruption	O
+of	O
+RB	B-GENE
+/	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+interaction	O
+by	O
+single	O
+point	O
+mutations	O
+in	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+enhances	O
+S	O
+-	O
+phase	O
+entry	O
+and	O
+apoptosis	O
+.	O
+
+Apparent	O
+loss	O
+of	O
+differentiation	O
+markers	O
+characterizes	O
+advanced	O
+malignant	O
+neoplasms	O
+.	O
+
+The	O
+method	O
+has	O
+been	O
+satisfactorily	O
+applied	O
+to	O
+the	O
+determination	O
+of	O
+paracetamol	O
+in	O
+pharmaceutical	O
+formulations	O
+and	O
+biological	O
+fluids	O
+.	O
+
+These	O
+primers	O
+yielded	O
+a	O
+PCR	O
+product	O
+of	O
+a	O
+characteristic	O
+length	O
+within	O
+most	O
+Xanthomonas	O
+species	O
+and	O
+pathovars	O
+tested	O
+.	O
+
+Rad6	B-GENE
+mutants	I-GENE
+display	O
+a	O
+remarkably	O
+pleiotropic	O
+phenotype	O
+,	O
+implicating	O
+the	O
+protein	O
+in	O
+DNA	O
+damage	O
+-	O
+induced	O
+mutagenesis	O
+,	O
+postreplication	O
+repair	O
+,	O
+repression	O
+of	O
+retrotransposition	O
+,	O
+and	O
+sporulation	O
+.	O
+
+RNase	B-GENE
+protection	O
+assays	O
+revealed	O
+a	O
+correlation	O
+between	O
+the	O
+levels	O
+of	O
+dorsal	O
+and	O
+ventral	O
+skin	O
+expression	O
+with	O
+pigmentation	O
+/	O
+phaeomelanin	O
+phenotypes	O
+.	O
+
+Molecular	O
+cloning	O
+,	O
+expression	O
+pattern	O
+,	O
+and	O
+chromosomal	O
+localization	O
+of	O
+human	O
+CDKN2D	B-GENE
+/	O
+INK4d	B-GENE
+,	O
+an	O
+inhibitor	O
+of	O
+cyclin	B-GENE
+D	I-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+.	O
+
+Overproduction	O
+of	O
+HrcA	B-GENE
+protein	I-GENE
+from	O
+a	O
+second	O
+copy	O
+of	O
+hrcA	B-GENE
+derived	O
+from	O
+a	O
+plasmid	O
+(	O
+phrcA	B-GENE
++	O
+)	O
+in	O
+B	O
+.	O
+subtilis	O
+wild	O
+-	O
+type	O
+and	O
+delta	O
+hrcA	B-GENE
+strains	O
+prevented	O
+heat	O
+shock	O
+induction	O
+of	O
+the	O
+dnaK	B-GENE
+and	O
+groE	B-GENE
+operons	I-GENE
+at	O
+the	O
+level	O
+of	O
+transcription	O
+almost	O
+completely	O
+and	O
+strongly	O
+reduced	O
+the	O
+amounts	O
+of	O
+mRNA	O
+at	O
+a	O
+low	O
+temperature	O
+as	O
+well	O
+.	O
+
+We	O
+report	O
+the	O
+molecular	O
+cloning	O
+and	O
+functional	O
+characterization	O
+of	O
+USF2	B-GENE
+isoforms	I-GENE
+,	O
+corresponding	O
+to	O
+a	O
+44	O
+-	O
+kDa	O
+subunit	O
+,	O
+USF2a	B-GENE
+,	O
+and	O
+a	O
+new	O
+38	O
+-	O
+kDa	O
+subunit	O
+,	O
+USF2b	B-GENE
+,	O
+generated	O
+by	O
+differential	O
+splicing	O
+.	O
+
+The	O
+preferential	O
+heterodimerization	O
+of	O
+USF	B-GENE
+subunits	I-GENE
+was	O
+reproduced	O
+ex	O
+vivo	O
+,	O
+while	O
+the	O
+in	O
+vitro	O
+association	O
+of	O
+cotranslated	O
+subunits	O
+,	O
+or	O
+recombinant	B-GENE
+USF	I-GENE
+proteins	I-GENE
+,	O
+appeared	O
+to	O
+be	O
+random	O
+.	O
+
+Activated	O
+PKR	B-GENE
+may	O
+exist	O
+as	O
+a	O
+dimer	O
+and	O
+phosphorylates	O
+the	O
+eukaryotic	B-GENE
+translation	I-GENE
+initiation	I-GENE
+factor	I-GENE
+2	I-GENE
+alpha	I-GENE
+subunit	I-GENE
+(	O
+cIF	B-GENE
+-	I-GENE
+2	I-GENE
+alpha	I-GENE
+)	O
+to	O
+inhibit	O
+polypeptide	O
+chain	O
+initiation	O
+.	O
+
+GRP78	B-GENE
+,	O
+a	O
+molecular	O
+chaperone	O
+expressed	O
+in	O
+the	O
+endoplasmic	O
+reticulum	O
+,	O
+is	O
+a	O
+"	O
+glucose	O
+-	O
+regulated	O
+protein	O
+"	O
+induced	O
+by	O
+stress	O
+responses	O
+that	O
+deplete	O
+glucose	O
+or	O
+intracisternal	O
+calcium	O
+or	O
+otherwise	O
+disrupt	O
+glycoprotein	O
+trafficking	O
+.	O
+
+The	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+receptor	I-GENE
+is	O
+a	O
+seven	O
+-	O
+transmembrane	O
+spanning	O
+receptor	O
+coupled	O
+to	O
+specific	O
+heterotrimeric	B-GENE
+G	I-GENE
+proteins	I-GENE
+including	O
+Gi	B-GENE
+and	O
+G16	B-GENE
+.	O
+
+In	O
+a	O
+second	O
+series	O
+of	O
+experiments	O
+,	O
+the	O
+efficacy	O
+of	O
+PDC	O
+/	O
+HDC	O
+Ac	O
+was	O
+evaluated	O
+in	O
+both	O
+single	O
+and	O
+multiple	O
+dose	O
+regiments	O
+.	O
+
+To	O
+elucidate	O
+the	O
+functional	O
+significance	O
+of	O
+Fyn	B-GENE
+in	O
+the	O
+expression	O
+of	O
+viral	O
+promoters	O
+,	O
+we	O
+transfected	O
+a	O
+Fyn	B-GENE
+-	O
+expression	O
+vector	O
+together	O
+with	O
+a	O
+reporter	O
+plasmid	O
+containing	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+gene	I-GENE
+driven	O
+by	O
+HIV	B-GENE
+LTR	I-GENE
+into	O
+a	O
+human	O
+T	O
+cell	O
+line	O
+,	O
+Jurkat	O
+.	O
+
+We	O
+conducted	O
+a	O
+prospective	O
+,	O
+randomized	O
+controlled	O
+trial	O
+of	O
+metoprolol	O
+,	O
+a	O
+selective	O
+beta	O
+-	O
+blocker	O
+for	O
+prevention	O
+of	O
+gastrointestinal	O
+bleeding	O
+from	O
+portal	O
+hypertension	O
+in	O
+29	O
+non	O
+-	O
+selected	O
+patients	O
+with	O
+liver	O
+disease	O
+and	O
+previous	O
+gastrointestinal	O
+bleeding	O
+.	O
+
+A	O
+genetic	O
+and	O
+molecular	O
+analysis	O
+of	O
+non	O
+-	O
+inducible	O
+qutA	B-GENE
+mutants	I-GENE
+showed	O
+that	O
+all	O
+23	O
+mutations	O
+analysed	O
+map	O
+within	O
+the	O
+N	O
+-	O
+terminal	O
+half	O
+of	O
+the	O
+encoded	O
+QUTA	B-GENE
+protein	I-GENE
+.	O
+
+These	O
+studies	O
+indicate	O
+that	O
+the	O
+acidimetric	O
+test	O
+was	O
+less	O
+sensitive	O
+than	O
+the	O
+chromogenic	O
+cephalosporin	O
+substrates	O
+and	O
+that	O
+nitrocefin	O
+and	O
+S1	O
+could	O
+be	O
+used	O
+to	O
+screen	O
+for	O
+beta	B-GENE
+-	I-GENE
+lactamase	I-GENE
+production	O
+in	O
+these	O
+tested	O
+species	O
+.	O
+
+Suppressors	O
+of	O
+defective	O
+silencing	O
+in	O
+yeast	O
+:	O
+effects	O
+on	O
+transcriptional	O
+repression	O
+at	O
+the	O
+HMR	B-GENE
+locus	I-GENE
+,	O
+cell	O
+growth	O
+and	O
+telomere	O
+structure	O
+.	O
+
+Although	O
+ANP	B-GENE
+induced	O
+systemic	O
+capillary	O
+filtration	O
+,	O
+in	O
+the	O
+calf	O
+,	O
+filtration	O
+was	O
+reduced	O
+with	O
+ANP	B-GENE
+.	O
+
+Recent	O
+literature	O
+has	O
+suggested	O
+that	O
+beta	B-GENE
+-	I-GENE
+2	I-GENE
+transferrin	I-GENE
+can	O
+also	O
+be	O
+used	O
+as	O
+a	O
+clinical	O
+marker	O
+for	O
+perilymph	O
+.	O
+
+With	O
+current	O
+methodology	O
+beta	B-GENE
+-	I-GENE
+2	I-GENE
+transferrin	I-GENE
+does	O
+not	O
+appear	O
+to	O
+be	O
+a	O
+reliable	O
+clinical	O
+marker	O
+for	O
+perilymph	O
+in	O
+the	O
+operative	O
+setting	O
+.	O
+
+The	O
+hIGF	B-GENE
+-	I-GENE
+I	I-GENE
+gene	I-GENE
+has	O
+two	O
+promoters	O
+,	O
+P1	O
+and	O
+P2	O
+.	O
+
+Gel	O
+mobility	O
+shift	O
+assays	O
+indicated	O
+that	O
+at	O
+least	O
+four	O
+nuclear	O
+proteins	O
+with	O
+distinct	O
+biochemical	O
+and	O
+binding	O
+properties	O
+possess	O
+the	O
+ability	O
+to	O
+bind	O
+the	O
+3	O
+beta	O
+I	O
+-	O
+A	O
+element	O
+to	O
+produce	O
+four	O
+DNA	O
+-	O
+protein	O
+complexes	O
+(	O
+R1	O
+to	O
+R4	O
+)	O
+.	O
+
+Sixty	O
+-	O
+five	O
+patients	O
+(	O
+aged	O
+between	O
+3	O
+years	O
+5	O
+months	O
+and	O
+60	O
+years	O
+)	O
+suffering	O
+from	O
+medically	O
+resistant	O
+temporal	O
+lobe	O
+epilepsy	O
+(	O
+TLE	O
+)	O
+were	O
+operated	O
+on	O
+over	O
+a	O
+period	O
+of	O
+33	O
+months	O
+in	O
+Bethel	O
+Epilepsy	O
+Center	O
+.	O
+
+Significant	O
+correlations	O
+existed	O
+between	O
+FEV1	O
+and	O
+the	O
+corresponding	O
+values	O
+of	O
+Raw	O
+,	O
+MEF50	O
+and	O
+MEF25	O
+,	O
+although	O
+there	O
+were	O
+considerable	O
+individual	O
+differences	O
+between	O
+test	O
+results	O
+.	O
+
+Hybrid	O
+female	O
+mice	O
+(	O
+C57BL	O
+x	O
+CBA	O
+)	O
+were	O
+paired	O
+with	O
+breeder	O
+males	O
+(	O
+CD	O
+-	O
+1	O
+)	O
+and	O
+LNG	O
+pellets	O
+were	O
+implanted	O
+on	O
+day	O
+0	O
+,	O
+the	O
+day	O
+on	O
+which	O
+copulation	O
+plugs	O
+were	O
+found	O
+,	O
+or	O
+on	O
+day	O
+2	O
+or	O
+day	O
+3	O
+in	O
+the	O
+postcoital	O
+period	O
+.	O
+
+This	O
+gene	O
+encodes	O
+a	O
+putative	O
+transcription	O
+factor	O
+with	O
+regions	O
+of	O
+homology	O
+to	O
+several	O
+other	O
+proteins	O
+including	O
+the	O
+zinc	O
+fingers	O
+and	O
+other	O
+domains	O
+of	O
+the	O
+Drosophila	B-GENE
+trithorax	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+and	O
+the	O
+"	O
+AT	O
+-	O
+hook	O
+"	O
+DNA	O
+-	O
+binding	O
+motif	O
+of	O
+high	B-GENE
+mobility	I-GENE
+group	I-GENE
+proteins	I-GENE
+.	O
+
+Using	O
+reference	O
+probes	O
+as	O
+internal	O
+standards	O
+,	O
+we	O
+show	O
+that	O
+the	O
+ost	B-GENE
+transcription	I-GENE
+unit	I-GENE
+is	O
+located	O
+within	O
+the	O
+cytogenetic	O
+band	O
+interval	O
+89A1	O
+,	O
+2	O
+on	O
+the	O
+right	O
+arm	O
+of	O
+the	O
+third	O
+chromosome	O
+,	O
+and	O
+that	O
+it	O
+exerts	O
+diagnostic	O
+segmentation	O
+gene	O
+expression	O
+patterns	O
+in	O
+the	O
+embryo	O
+.	O
+
+The	O
+purified	O
+recombinant	O
+enzyme	O
+catalyzed	O
+specific	O
+phosphoryl	O
+transfer	O
+from	O
+ATP	O
+to	O
+UMP	O
+and	O
+CMP	O
+.	O
+
+Studies	O
+on	O
+the	O
+life	O
+cycle	O
+of	O
+Haplorchis	O
+pumilio	O
+(	O
+Looss	O
+,	O
+1896	O
+)	O
+Looss	O
+,	O
+1899	O
+with	O
+morphological	O
+redescription	O
+of	O
+larval	O
+and	O
+adult	O
+stages	O
+.	O
+
+Regressing	O
+microaneurysms	O
+in	O
+5	O
+cases	O
+of	O
+hepatitis	O
+B	O
+virus	O
+related	O
+polyarteritis	O
+nodosa	O
+.	O
+
+During	O
+the	O
+following	O
+pregnancy	O
+ultrasonographic	O
+studies	O
+of	O
+the	O
+male	O
+fetus	O
+in	O
+the	O
+16th	O
+week	O
+of	O
+gestation	O
+revealed	O
+severe	O
+micrognathia	O
+,	O
+short	O
+and	O
+wide	O
+thumbs	O
+,	O
+and	O
+big	O
+toes	O
+,	O
+and	O
+bowed	O
+tibiae	O
+.	O
+
+Despite	O
+an	O
+overall	O
+survival	O
+rate	O
+of	O
+43	O
+%	O
+,	O
+survival	O
+to	O
+discharge	O
+varied	O
+greatly	O
+(	O
+0	O
+to	O
+100	O
+%	O
+)	O
+among	O
+the	O
+24	O
+diagnostic	O
+groups	O
+:	O
+tumor	O
+lysis	O
+syndrome	O
+and	O
+systemic	O
+lupus	O
+erythematosus	O
+(	O
+3	O
+/	O
+3	O
+patients	O
+each	O
+,	O
+100	O
+%	O
+)	O
+,	O
+hemolytic	O
+uremic	O
+syndrome	O
+(	O
+8	O
+/	O
+9	O
+patients	O
+,	O
+89	O
+%	O
+)	O
+.	O
+
+One	O
+hundred	O
+units	O
+/	O
+kg	O
+of	O
+recombinant	B-GENE
+human	I-GENE
+erythropoietin	I-GENE
+(	O
+rhEPO	B-GENE
+)	O
+was	O
+given	O
+subcutaneously	O
+3	O
+times	O
+a	O
+week	O
+for	O
+3	O
+weeks	O
+.	O
+
+A	O
+3	O
+-	O
+week	O
+regimen	O
+of	O
+erythropoietin	B-GENE
+may	O
+help	O
+prevent	O
+the	O
+donor	O
+'	O
+s	O
+need	O
+to	O
+receive	O
+allogeneic	O
+blood	O
+transfusion	O
+,	O
+when	O
+the	O
+initial	O
+Hb	B-GENE
+levels	O
+were	O
+below	O
+130	O
+milligrams	O
+.	O
+
+The	O
+mean	O
+body	O
+mass	O
+index	O
+(	O
+BMI	O
+)	O
+was	O
+31	O
+.	O
+8	O
++	O
+/	O
+-	O
+6	O
+.	O
+3	O
+kg	O
+/	O
+m2	O
+and	O
+28	O
+.	O
+5	O
++	O
+/	O
+-	O
+6	O
+.	O
+3	O
+kg	O
+/	O
+m2	O
+in	O
+women	O
+and	O
+men	O
+,	O
+respectively	O
+.	O
+
+These	O
+findings	O
+demonstrate	O
+that	O
+haemodialysis	O
+patients	O
+with	O
+chronic	O
+hepatitis	O
+C	O
+respond	O
+well	O
+to	O
+interferon	B-GENE
+treatment	O
+and	O
+that	O
+a	O
+long	O
+-	O
+term	O
+response	O
+is	O
+achieved	O
+in	O
+a	O
+high	O
+proportion	O
+of	O
+patients	O
+.	O
+
+Synthetic	O
+enantiomers	O
+of	O
+drugs	O
+
+Polysome	O
+analysis	O
+further	O
+indicated	O
+that	O
+these	O
+germ	B-GENE
+cell	I-GENE
+-	I-GENE
+specific	I-GENE
+Sp1	I-GENE
+mRNAs	I-GENE
+are	O
+translated	O
+,	O
+albeit	O
+with	O
+a	O
+lower	O
+efficiency	O
+than	O
+the	O
+somatic	O
+transcript	O
+.	O
+
+In	O
+nondiabetics	O
+the	O
+response	O
+of	O
+tcPO2	O
+but	O
+not	O
+of	O
+LDF	O
+was	O
+influenced	O
+by	O
+the	O
+values	O
+at	O
+rest	O
+.	O
+
+This	O
+study	O
+proposes	O
+an	O
+estimator	O
+for	O
+such	O
+global	O
+synchronizing	O
+effects	O
+upon	O
+unit	O
+-	O
+pair	O
+correlations	O
+based	O
+on	O
+local	O
+field	O
+potentials	O
+(	O
+LFPs	O
+)	O
+.	O
+
+The	O
+assembly	O
+of	O
+sequence	O
+ready	O
+,	O
+high	O
+-	O
+resolution	O
+physical	O
+maps	O
+and	O
+construction	O
+of	O
+minimally	O
+overlapping	O
+contigs	O
+for	O
+the	O
+human	O
+as	O
+well	O
+as	O
+model	O
+genomes	O
+requires	O
+accurate	O
+determination	O
+of	O
+the	O
+extent	O
+of	O
+overlap	O
+between	O
+adjacent	O
+clones	O
+as	O
+well	O
+as	O
+their	O
+relative	O
+orientation	O
+.	O
+
+The	O
+DNA	O
+sequences	O
+upstream	O
+of	O
+these	O
+termini	O
+exhibit	O
+homology	O
+to	O
+plant	O
+mitochondrial	O
+-	O
+processing	O
+sites	O
+,	O
+therefore	O
+the	O
+proximal	O
+5	O
+'	O
+ends	O
+are	O
+most	O
+probably	O
+generated	O
+by	O
+RNA	O
+processing	O
+.	O
+
+Curing	O
+shrinkage	O
+and	O
+volumetric	O
+changes	O
+of	O
+resin	O
+-	O
+modified	O
+glass	O
+ionomer	O
+restorative	O
+materials	O
+.	O
+
+Here	O
+we	O
+present	O
+genetic	O
+evidence	O
+suggesting	O
+that	O
+PP2A	B-GENE
+functions	O
+downstream	O
+of	O
+Ras1	B-GENE
+in	O
+the	O
+Sevenless	B-GENE
+receptor	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+(	O
+RTK	B-GENE
+)	O
+signal	O
+transduction	O
+pathway	O
+that	O
+specifies	O
+R7	O
+photoreceptor	O
+cell	O
+fate	O
+in	O
+the	O
+developing	O
+Drosophila	O
+eye	O
+.	O
+
+QBMDs	O
+for	O
+a	O
+5	O
+%	O
+change	O
+in	O
+response	O
+(	O
+QBMD05	O
+)	O
+were	O
+6	O
+-	O
+fold	O
+lower	O
+,	O
+on	O
+average	O
+,	O
+than	O
+the	O
+corresponding	O
+NOAEL	O
+.	O
+
+The	O
+gene	O
+encodes	O
+an	O
+ATP	B-GENE
+-	I-GENE
+binding	I-GENE
+cassette	I-GENE
+,	O
+ABC	B-GENE
+transporter	I-GENE
+.	O
+
+The	O
+T	O
+-	O
+box	O
+motif	O
+is	O
+present	O
+in	O
+a	O
+family	O
+of	O
+genes	O
+whose	O
+structural	O
+features	O
+and	O
+expression	O
+patterns	O
+support	O
+their	O
+involvement	O
+in	O
+developmental	O
+gene	O
+regulation	O
+.	O
+
+Molecular	O
+analysis	O
+of	O
+a	O
+novel	O
+schizosaccharomyces	O
+pombe	O
+gene	O
+containing	O
+two	O
+RNP	O
+consensus	O
+-	O
+sequence	O
+RNA	O
+-	O
+binding	O
+domains	O
+.	O
+
+Do	O
+overall	O
+treatment	O
+time	O
+,	O
+field	O
+size	O
+,	O
+and	O
+treatment	O
+energy	O
+influence	O
+local	O
+control	O
+of	O
+T1	O
+-	O
+T2	O
+squamous	O
+cell	O
+carcinomas	O
+of	O
+the	O
+glottic	O
+larynx	O
+?	O
+PURPOSE	O
+:	O
+To	O
+evaluate	O
+treatment	O
+and	O
+patient	O
+related	O
+prognostic	O
+factors	O
+that	O
+may	O
+influence	O
+local	O
+control	O
+in	O
+the	O
+treatment	O
+of	O
+T1	O
+-	O
+T2	O
+squamous	O
+cell	O
+carcinoma	O
+of	O
+the	O
+glottic	O
+larynx	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+signaling	O
+triggered	O
+by	O
+surface	O
+Ig	B-GENE
+engagement	O
+in	O
+B	O
+lymphocytes	O
+,	O
+CD38	B-GENE
+ligation	O
+did	O
+not	O
+appear	O
+to	O
+induce	O
+tyrosine	O
+phosphorylation	O
+of	O
+the	O
+src	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+lyn	B-GENE
+,	O
+fyn	B-GENE
+,	O
+and	O
+btk	B-GENE
+,	O
+or	O
+of	O
+vav	B-GENE
+-	I-GENE
+and	I-GENE
+ras	I-GENE
+-	I-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+,	O
+nor	O
+did	O
+it	O
+induce	O
+detectable	O
+changes	O
+in	O
+cytosolic	O
+CA2	O
++	O
+concentrations	O
+.	O
+
+Mutations	O
+in	O
+the	O
+alpha	B-GENE
+-	I-GENE
+amanitin	I-GENE
+conserved	O
+domain	O
+of	O
+the	O
+largest	O
+subunit	O
+of	O
+yeast	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+III	I-GENE
+affect	O
+pausing	O
+,	O
+RNA	O
+cleavage	O
+and	O
+transcriptional	O
+transitions	O
+.	O
+
+The	O
+evidence	O
+presented	O
+here	O
+suggests	O
+that	O
+the	O
+p40	B-GENE
+complex	I-GENE
+is	O
+a	O
+ribonucleoprotein	O
+complex	O
+containing	O
+L1Hs	B-GENE
+RNA	I-GENE
+(	I-GENE
+s	I-GENE
+)	I-GENE
+and	O
+that	O
+protein	O
+-	O
+protein	O
+interactions	O
+in	O
+which	O
+alpha	O
+-	O
+helix	O
+structures	O
+participate	O
+,	O
+for	O
+example	O
+coiled	O
+-	O
+coils	O
+,	O
+may	O
+occur	O
+in	O
+the	O
+complex	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+trans	O
+-	O
+activation	O
+from	O
+the	O
+prothymosin	B-GENE
+intron	I-GENE
+enhancer	I-GENE
+is	O
+a	O
+faithful	O
+reflection	O
+of	O
+the	O
+transforming	O
+properties	O
+of	O
+the	O
+Myc	B-GENE
+protein	I-GENE
+.	O
+
+The	O
+5	O
+'	O
+external	O
+transcribed	O
+spacer	O
+(	O
+ETS	O
+)	O
+region	O
+of	O
+the	O
+pre	O
+-	O
+rRNA	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+contains	O
+a	O
+sequence	O
+with	O
+10	O
+bp	O
+of	O
+perfect	O
+complementarity	O
+to	O
+the	O
+U3	B-GENE
+snoRNA	I-GENE
+.	O
+
+These	O
+animals	O
+were	O
+viable	O
+and	O
+fertile	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+RPF	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+likely	O
+to	O
+be	O
+involved	O
+in	O
+early	O
+steps	O
+in	O
+the	O
+differentiation	O
+of	O
+amacrine	O
+and	O
+ganglion	O
+cells	O
+.	O
+
+Carboxy	O
+-	O
+terminal	O
+Spc110p	B-GENE
+truncations	O
+lacking	O
+the	O
+calmodulin	B-GENE
+binding	O
+site	O
+can	O
+support	O
+growth	O
+and	O
+are	O
+also	O
+phosphorylated	O
+in	O
+a	O
+cell	O
+cycle	O
+-	O
+specific	O
+manner	O
+.	O
+
+Both	O
+EWS	B-GENE
+-	O
+FLI	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+FLI	B-GENE
+-	I-GENE
+1	I-GENE
+proteins	I-GENE
+function	O
+as	O
+transcription	O
+factors	O
+that	O
+bind	O
+specifically	O
+to	O
+ets	B-GENE
+sequences	O
+(	O
+the	O
+ets	B-GENE
+boxes	O
+)	O
+present	O
+in	O
+promoter	O
+elements	O
+.	O
+
+In	O
+electromobility	O
+shift	O
+assays	O
+,	O
+EWS	B-GENE
+-	O
+FLI	B-GENE
+-	I-GENE
+1	I-GENE
+binding	O
+to	O
+the	O
+SRE	O
+is	O
+detectable	O
+in	O
+the	O
+absence	O
+of	O
+SRF	B-GENE
+whereas	O
+the	O
+binding	O
+of	O
+FLI	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+not	O
+,	O
+suggesting	O
+that	O
+the	O
+interaction	O
+with	O
+DNA	O
+is	O
+the	O
+step	O
+which	O
+limits	O
+ternary	O
+complex	O
+formation	O
+by	O
+FLI	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Additional	O
+studies	O
+with	O
+new	O
+and	O
+reprocessed	O
+regenerated	O
+cellulose	O
+dialyzers	O
+comparing	O
+450	O
+and	O
+220	O
+mL	O
+/	O
+min	O
+blood	O
+flow	O
+rates	O
+at	O
+10	O
+minutes	O
+showed	O
+no	O
+change	O
+in	O
+BTG	O
+.	O
+
+DNA	O
+methylation	O
+,	O
+especially	O
+of	O
+either	O
+one	O
+or	O
+both	O
+of	O
+the	O
+deoxyadenosines	O
+at	O
+the	O
+two	O
+GATC	O
+motifs	O
+(	O
+one	O
+in	O
+the	O
+first	O
+exon	O
+and	O
+the	O
+other	O
+in	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+rice	O
+CatA	B-GENE
+gene	I-GENE
+)	O
+,	O
+appeared	O
+to	O
+be	O
+responsible	O
+for	O
+the	O
+CatA	B-GENE
+promoter	I-GENE
+activity	O
+identified	O
+in	O
+the	O
+transient	O
+assay	O
+.	O
+
+The	O
+viral	B-GENE
+LTR	I-GENE
+was	O
+used	O
+as	O
+the	O
+promoter	O
+.	O
+
+Overlapping	O
+cDNA	O
+clones	O
+were	O
+isolated	O
+and	O
+sequenced	O
+.	O
+
+Epitope	O
+mapping	O
+revealed	O
+that	O
+these	O
+three	O
+clones	O
+appear	O
+to	O
+recognize	O
+an	O
+identical	O
+epitope	O
+domain	O
+present	O
+on	O
+the	O
+C	O
+-	O
+terminal	O
+RNP	O
+motif	O
+of	O
+the	O
+U1A	B-GENE
+protein	I-GENE
+.	O
+
+Variables	O
+evaluated	O
+were	O
+number	O
+of	O
+weekly	O
+anginal	O
+events	O
+,	O
+data	O
+from	O
+ergometric	O
+exercise	O
+testing	O
+with	O
+simultaneous	O
+electrocardiographic	O
+registration	O
+,	O
+semiquantitative	O
+evaluation	O
+of	O
+Tc	O
+-	O
+99m	O
+2	O
+-	O
+methoxy	O
+isobutyl	O
+isonitrile	O
+(	O
+MIBI	O
+)	O
+scans	O
+and	O
+rheologic	O
+variables	O
+.	O
+
+As	O
+the	O
+length	O
+of	O
+the	O
+fatty	O
+acid	O
+decreased	O
+,	O
+the	O
+binding	O
+affinity	O
+was	O
+reduced	O
+;	O
+myristic	O
+acid	O
+(	O
+14	O
+:	O
+0	O
+)	O
+bound	O
+with	O
+a	O
+K	O
+(	O
+d	O
+)	O
+of	O
+1409	O
++	O
+/	O
+-	O
+423	O
+nM	O
+,	O
+but	O
+medium	O
+-	O
+chain	O
+(	O
+decanoic	O
+acid	O
+,	O
+10	O
+:	O
+0	O
+)	O
+and	O
+short	O
+-	O
+chain	O
+(	O
+octanoic	O
+acid	O
+,	O
+8	O
+:	O
+0	O
+)	O
+lipids	O
+were	O
+not	O
+bound	O
+at	O
+all	O
+.	O
+
+The	O
+membrane	O
+-	O
+distal	O
+cytoplasmic	O
+region	O
+of	O
+human	B-GENE
+granulocyte	I-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+receptor	I-GENE
+is	O
+required	O
+for	O
+STAT3	B-GENE
+but	O
+not	O
+STAT1	B-GENE
+homodimer	I-GENE
+formation	O
+.	O
+
+However	O
+,	O
+whether	O
+or	O
+not	O
+nonsense	O
+codon	O
+recognition	O
+within	O
+TPI	B-GENE
+transcripts	I-GENE
+takes	O
+place	O
+prior	O
+to	O
+or	O
+after	O
+splicing	O
+remained	O
+unresolved	O
+.	O
+
+Although	O
+some	O
+residues	O
+are	O
+found	O
+reactive	O
+toward	O
+dimethylsulphate	O
+and	O
+kethoxal	O
+in	O
+regions	O
+predicted	O
+to	O
+be	O
+unpaired	O
+by	O
+the	O
+phylogenetic	O
+secondary	O
+structure	O
+model	O
+of	O
+4	B-GENE
+.	I-GENE
+5S	I-GENE
+RNA	I-GENE
+,	O
+generally	O
+the	O
+reactivity	O
+is	O
+low	O
+,	O
+and	O
+some	O
+residues	O
+in	O
+internal	O
+loops	O
+are	O
+not	O
+reactive	O
+at	O
+all	O
+.	O
+
+Ongoing	O
+and	O
+future	O
+investigations	O
+may	O
+better	O
+define	O
+the	O
+optimal	O
+approach	O
+for	O
+local	O
+control	O
+,	O
+the	O
+optimal	O
+duration	O
+of	O
+maintenance	O
+chemotherapy	O
+,	O
+and	O
+the	O
+possible	O
+role	O
+of	O
+biologic	O
+response	O
+modifiers	O
+and	O
+growth	O
+factors	O
+in	O
+further	O
+improving	O
+the	O
+outcome	O
+for	O
+patients	O
+with	O
+this	O
+disease	O
+.	O
+
+SUMMARY	O
+OF	O
+REVIEW	O
+:	O
+We	O
+discuss	O
+the	O
+criteria	O
+that	O
+make	O
+such	O
+studies	O
+comparable	O
+,	O
+drawing	O
+on	O
+the	O
+experiences	O
+of	O
+recent	O
+studies	O
+performed	O
+around	O
+the	O
+world	O
+.	O
+
+Forty	O
+-	O
+five	O
+patients	O
+with	O
+pleural	O
+lesions	O
+identified	O
+on	O
+CT	O
+scans	O
+were	O
+subsequently	O
+examined	O
+by	O
+MR	O
+imaging	O
+at	O
+0	O
+.	O
+5	O
+T	O
+.	O
+
+RESULTS	O
+:	O
+Basal	O
+plasma	B-GENE
+IGF	I-GENE
+-	I-GENE
+I	I-GENE
+levels	O
+as	O
+well	O
+as	O
+body	O
+mass	O
+index	O
+(	O
+BMI	O
+)	O
+were	O
+lower	O
+in	O
+amenorrheic	O
+patients	O
+than	O
+in	O
+healthy	O
+controls	O
+.	O
+
+The	O
+alpha	O
+T3	O
+-	O
+1	O
+cell	O
+line	O
+,	O
+a	O
+GnRH	B-GENE
+-	O
+responsive	O
+gonadotroph	O
+cell	O
+line	O
+developed	O
+by	O
+targeted	O
+oncogenesis	O
+in	O
+transgenic	O
+mice	O
+,	O
+was	O
+used	O
+to	O
+study	O
+regulation	O
+of	O
+the	O
+glycoprotein	B-GENE
+hormone	I-GENE
+alpha	I-GENE
+-	I-GENE
+subunit	I-GENE
+by	O
+activin	B-GENE
+.	O
+
+Cotransfection	O
+with	O
+the	O
+ie1	B-GENE
+gene	I-GENE
+resulted	O
+in	O
+a	O
+dramatic	O
+increase	O
+in	O
+the	O
+amount	O
+of	O
+the	O
+two	O
+enzymes	O
+expressed	O
+in	O
+the	O
+transfected	O
+cells	O
+.	O
+
+As	O
+expected	O
+,	O
+glycosylation	O
+of	O
+Env	B-GENE
+produced	O
+from	O
+mutants	O
+was	O
+affected	O
+but	O
+,	O
+irrespective	O
+of	O
+the	O
+glycosylation	O
+phenotype	O
+,	O
+(	O
+i	O
+)	O
+similar	O
+quantities	O
+of	O
+Env	B-GENE
+were	O
+synthesized	O
+,	O
+(	O
+ii	O
+)	O
+the	O
+immunoreactivity	O
+of	O
+V3	B-GENE
+was	O
+similar	O
+,	O
+(	O
+iii	O
+)	O
+gp160	B-GENE
+was	O
+efficiently	O
+cleaved	O
+into	O
+gp120	B-GENE
+and	O
+gp41	B-GENE
+,	O
+(	O
+vi	O
+)	O
+Env	B-GENE
+was	O
+exposed	O
+at	O
+the	O
+cell	O
+membrane	O
+,	O
+(	O
+v	O
+)	O
+secreted	O
+gp120	B-GENE
+bound	O
+CD4	B-GENE
+,	O
+and	O
+(	O
+vi	O
+)	O
+membrane	O
+gp41	B-GENE
+was	O
+able	O
+to	O
+induce	O
+membrane	O
+fusion	O
+with	O
+CD4	B-GENE
++	I-GENE
+cells	O
+.	O
+
+Effects	O
+of	O
+posteroventral	O
+pallidotomy	O
+on	O
+Parkinson	O
+'	O
+s	O
+disease	O
+.	O
+
+On	O
+the	O
+trail	O
+of	O
+Dr	O
+.	O
+
+However	O
+,	O
+only	O
+complete	B-GENE
+DnaJ	I-GENE
+can	O
+cooperate	O
+with	O
+DnaK	B-GENE
+and	O
+a	O
+third	O
+protein	O
+,	O
+GrpE	B-GENE
+,	O
+in	O
+refolding	O
+denatured	B-GENE
+firefly	I-GENE
+luciferase	I-GENE
+.	O
+
+The	O
+two	O
+different	O
+phosphoforms	O
+of	O
+STAT5	B-GENE
+have	O
+identical	O
+in	O
+vitro	O
+DNA	O
+binding	O
+specificity	O
+and	O
+reactivity	O
+with	O
+tyrosine	O
+phosphopeptides	O
+,	O
+but	O
+differ	O
+in	O
+their	O
+cellular	O
+localization	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+novel	O
+protein	O
+from	O
+Drosophila	O
+nuclear	O
+extracts	O
+which	O
+binds	O
+specifically	O
+to	O
+a	O
+site	O
+in	O
+this	O
+second	O
+region	O
+.	O
+
+Control	O
+of	O
+transcription	O
+of	O
+the	O
+erbB	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+is	O
+an	O
+important	O
+determinant	O
+of	O
+receptor	O
+expression	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+indicate	O
+that	O
+PBP	B-GENE
+binds	O
+to	O
+the	O
+half	O
+-	O
+site	O
+of	O
+each	O
+palindrome	O
+with	O
+the	O
+core	O
+recognition	O
+sequence	O
+TGGGAG	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+sequences	O
+in	O
+the	O
+SH2	B-GENE
+/	O
+SH3	B-GENE
+/	O
+SH2	B-GENE
+region	O
+of	O
+p120	B-GENE
+GAP	B-GENE
+are	O
+required	O
+for	O
+full	O
+catalytic	O
+activity	O
+toward	O
+Ras	B-GENE
+.	O
+
+Further	O
+analysis	O
+of	O
+this	O
+domain	O
+by	O
+in	O
+vitro	O
+mutagenesis	O
+pointed	O
+to	O
+a	O
+core	O
+of	O
+hydrophobic	O
+and	O
+acidic	O
+residues	O
+as	O
+critical	O
+for	O
+the	O
+activity	O
+.	O
+
+Analysis	O
+of	O
+RAR	B-GENE
+alpha	I-GENE
+mutants	I-GENE
+in	O
+transfection	O
+studies	O
+reveals	O
+that	O
+the	O
+DNA	O
+binding	O
+domain	O
+is	O
+sufficient	O
+for	O
+inhibition	O
+of	O
+BZLF1	B-GENE
+activity	O
+.	O
+
+We	O
+measured	O
+serum	B-GENE
+hepatocyte	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+HGF	B-GENE
+)	O
+in	O
+patients	O
+with	O
+acute	O
+myocardial	O
+infarction	O
+,	O
+angina	O
+pectoris	O
+,	O
+and	O
+other	O
+heart	O
+diseases	O
+.	O
+
+The	O
+neural	O
+mechanism	O
+of	O
+parkinsonian	O
+motor	O
+symptoms	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+rigidity	O
+,	O
+tremor	O
+and	O
+akinesia	O
+,	O
+which	O
+are	O
+the	O
+result	O
+of	O
+nigrostriatal	O
+dopamine	O
+deficiency	O
+,	O
+is	O
+interpreted	O
+from	O
+long	O
+-	O
+term	O
+observations	O
+on	O
+the	O
+effect	O
+of	O
+surgical	O
+and	O
+pharmacological	O
+treatment	O
+of	O
+the	O
+disease	O
+in	O
+relation	O
+to	O
+the	O
+neuropathological	O
+findings	O
+within	O
+the	O
+substantia	O
+nigra	O
+zona	O
+compacta	O
+(	O
+SNc	O
+)	O
+.	O
+
+Protein	O
+splicing	O
+:	O
+evidence	O
+for	O
+an	O
+N	O
+-	O
+O	O
+acyl	O
+rearrangement	O
+as	O
+the	O
+initial	O
+step	O
+in	O
+the	O
+splicing	O
+process	O
+.	O
+
+In	O
+agreement	O
+with	O
+these	O
+data	O
+,	O
+western	O
+blot	O
+experiments	O
+using	O
+an	O
+antibody	O
+directed	O
+against	O
+the	O
+carboxy	O
+-	O
+terminal	O
+portion	O
+of	O
+the	O
+mouse	O
+c	B-GENE
+-	I-GENE
+kit	I-GENE
+protein	I-GENE
+showed	O
+that	O
+a	O
+polypeptide	O
+,	O
+of	O
+the	O
+size	O
+predicted	O
+by	O
+the	O
+open	O
+reading	O
+frame	O
+of	O
+the	O
+spermatid	B-GENE
+-	I-GENE
+specific	I-GENE
+c	I-GENE
+-	I-GENE
+kit	I-GENE
+cDNA	I-GENE
+,	O
+accumulates	O
+in	O
+the	O
+latest	O
+stages	O
+of	O
+spermatogenesis	O
+and	O
+in	O
+epididymal	O
+spermatozoa	O
+.	O
+
+It	O
+is	O
+shown	O
+that	O
+the	O
+(	O
+G	O
++	O
+C	O
+)	O
+-	O
+rich	O
+element	O
+of	O
+the	O
+aldolase	B-GENE
+C	I-GENE
+promoter	I-GENE
+directs	O
+transcription	O
+in	O
+neuronal	O
+as	O
+well	O
+as	O
+in	O
+nonneuronal	O
+cells	O
+.	O
+
+Treatment	O
+of	O
+keratinocytes	O
+expressing	O
+a	O
+normal	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+(	O
+EGFR	B-GENE
+)	O
+with	O
+TGFalpha	B-GENE
+or	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+for	O
+5	O
+min	O
+induced	O
+PKCdelta	B-GENE
+tyrosine	O
+phosphorylation	O
+.	O
+
+Only	O
+one	O
+of	O
+these	O
+bands	O
+was	O
+supershifted	O
+by	O
+antibody	O
+to	O
+p50	B-GENE
+,	O
+whereas	O
+antibodies	O
+to	O
+p65	B-GENE
+or	O
+other	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+proteins	I-GENE
+had	O
+no	O
+effect	O
+.	O
+
+We	O
+isolated	O
+a	O
+complementary	O
+DNA	O
+(	O
+cDNA	O
+)	O
+clone	O
+from	O
+an	O
+RL95	O
+-	O
+2	O
+expression	O
+library	O
+that	O
+encodes	O
+the	O
+C1	B-GENE
+site	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+Biol	O
+.	O
+
+In	O
+addition	O
+,	O
+anti	B-GENE
+-	I-GENE
+phosphotyrosine	I-GENE
+antibodies	I-GENE
+immunoprecipitated	O
+80K	B-GENE
+-	I-GENE
+H	I-GENE
+from	O
+cell	O
+lysates	O
+of	O
+FGF	B-GENE
+-	O
+stimulated	O
+but	O
+not	O
+from	O
+control	O
+fibroblasts	O
+.	O
+
+The	O
+novel	O
+protein	O
+kinases	O
+,	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+NH2	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinases	I-GENE
+(	O
+JNKs	B-GENE
+)	O
+/	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinases	I-GENE
+,	O
+are	O
+also	O
+activated	O
+by	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+,	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+CD28	B-GENE
+costimulation	O
+.	O
+
+Thus	O
+,	O
+hGRbeta	B-GENE
+potentially	O
+functions	O
+as	O
+a	O
+dominant	O
+negative	O
+inhibitor	O
+of	O
+hGRalpha	B-GENE
+activity	O
+.	O
+
+Gas6	B-GENE
+contains	O
+an	O
+NH2	O
+-	O
+terminal	O
+Gla	O
+domain	O
+followed	O
+by	O
+four	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+like	I-GENE
+repeats	I-GENE
+and	O
+tandem	O
+globular	O
+(	O
+G	O
+)	O
+domains	O
+.	O
+
+Both	O
+P5CDh	B-GENE
+cDNA	I-GENE
+clones	O
+detect	O
+a	O
+single	O
+3	O
+.	O
+2	O
+-	O
+kb	O
+transcript	O
+on	O
+Northern	O
+blots	O
+of	O
+multiple	O
+human	O
+tissues	O
+,	O
+indicating	O
+the	O
+long	O
+cDNA	O
+containing	O
+the	O
+3	O
+'	O
+-	O
+untranslated	O
+intron	O
+represents	O
+the	O
+predominant	O
+transcript	O
+.	O
+
+Polymerization	O
+of	O
+neurofilament	B-GENE
+L	I-GENE
+protein	I-GENE
+in	O
+vitro	O
+was	O
+inhibited	O
+by	O
+phosphorylation	O
+of	O
+neurofilament	B-GENE
+L	I-GENE
+protein	I-GENE
+by	O
+PKN	B-GENE
+.	O
+
+We	O
+and	O
+others	O
+have	O
+demonstrated	O
+that	O
+the	O
+c	B-GENE
+-	I-GENE
+cbl	I-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+product	I-GENE
+is	O
+one	O
+of	O
+the	O
+earliest	O
+targets	O
+of	O
+tyrosine	O
+phosphorylation	O
+upon	O
+T	B-GENE
+cell	I-GENE
+receptor	I-GENE
+stimulation	O
+.	O
+
+A	O
+substantial	O
+fraction	O
+of	O
+Cbl	B-GENE
+was	O
+constitutively	O
+associated	O
+with	O
+Grb2	B-GENE
+and	O
+this	O
+interaction	O
+was	O
+mediated	O
+by	O
+Grb2	B-GENE
+SH3	B-GENE
+domains	O
+.	O
+
+An	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+sequence	I-GENE
+is	O
+essential	O
+for	O
+regulation	O
+of	O
+the	O
+human	B-GENE
+alpha2	I-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+collagen	I-GENE
+(	O
+COL1A2	B-GENE
+)	O
+promoter	O
+activity	O
+by	O
+transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta	I-GENE
+.	O
+
+Only	O
+two	O
+patients	O
+(	O
+0	O
+.	O
+3	O
+%	O
+)	O
+had	O
+a	O
+CA	B-GENE
+125	I-GENE
+response	O
+at	O
+the	O
+time	O
+of	O
+clinical	O
+progression	O
+.	O
+
+The	O
+men	O
+self	O
+-	O
+selected	O
+a	O
+prescribed	O
+diet	O
+at	O
+home	O
+emphasizing	O
+saturated	O
+fat	O
+as	O
+the	O
+visible	O
+fat	O
+for	O
+1	O
+week	O
+.	O
+
+These	O
+results	O
+illuminate	O
+a	O
+hitherto	O
+unanticipated	O
+function	O
+of	O
+U6	B-GENE
+RNA	I-GENE
+:	O
+the	O
+modulation	O
+of	O
+a	O
+phosphorylation	O
+-	O
+dephosphorylation	O
+cycle	O
+of	O
+C1	B-GENE
+hnRNP	I-GENE
+protein	I-GENE
+that	O
+influences	O
+the	O
+binding	O
+affinity	O
+of	O
+this	O
+protein	O
+for	O
+pre	O
+-	O
+mRNA	O
+.	O
+
+Inclusion	O
+of	O
+the	O
+extended	O
+N	O
+terminus	O
+into	O
+the	O
+originally	O
+reported	O
+protein	O
+resulted	O
+in	O
+a	O
+striking	O
+similarity	O
+to	O
+the	O
+lymphoid	B-GENE
+factor	I-GENE
+Lef	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Truncated	O
+mammalian	B-GENE
+Notch1	I-GENE
+activates	O
+CBF1	B-GENE
+/	O
+RBPJk	B-GENE
+-	O
+repressed	O
+genes	O
+by	O
+a	O
+mechanism	O
+resembling	O
+that	O
+of	O
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+EBNA2	I-GENE
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+(	O
+EMSAs	O
+)	O
+using	O
+purified	O
+glucocorticoid	B-GENE
+receptor	I-GENE
+DNA	I-GENE
+binding	I-GENE
+domain	I-GENE
+(	O
+DBD	O
+)	O
+demonstrated	O
+that	O
+both	O
+GRE	B-GENE
+-	I-GENE
+2	I-GENE
+and	I-GENE
+-	I-GENE
+3	I-GENE
+motifs	I-GENE
+interact	O
+with	O
+DBD	O
+and	O
+oligonucleotide	O
+competition	O
+experiments	O
+established	O
+that	O
+these	O
+have	O
+different	O
+affinities	O
+for	O
+DBD	O
+.	O
+
+The	O
+large	O
+subfamily	O
+of	O
+receptor	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+(	O
+RTKs	B-GENE
+)	O
+for	O
+which	O
+EPH	B-GENE
+is	O
+the	O
+prototype	O
+have	O
+likely	O
+roles	O
+in	O
+intercellular	O
+communication	O
+during	O
+normal	O
+mammalian	O
+development	O
+,	O
+but	O
+the	O
+biochemical	O
+signalling	O
+pathways	O
+utilised	O
+by	O
+this	O
+family	O
+are	O
+poorly	O
+characterised	O
+.	O
+
+The	O
+17	O
+-	O
+kDa	O
+protein	O
+is	O
+required	O
+for	O
+the	O
+systemic	O
+infection	O
+of	O
+plants	O
+.	O
+
+We	O
+present	O
+here	O
+a	O
+detailed	O
+genomic	O
+sequencing	O
+analysis	O
+of	O
+the	O
+cytosine	O
+methylation	O
+patterns	O
+of	O
+the	O
+transposase	B-GENE
+binding	O
+sites	O
+within	O
+both	O
+Ac	B-GENE
+ends	O
+in	O
+the	O
+wx	B-GENE
+-	I-GENE
+m9	I-GENE
+:	O
+:	O
+Ac	B-GENE
+allele	I-GENE
+,	O
+where	O
+Ac	B-GENE
+is	O
+inserted	O
+into	O
+the	O
+tenth	O
+exon	O
+of	O
+the	O
+Waxy	B-GENE
+gene	I-GENE
+.	O
+
+Krox	B-GENE
+-	I-GENE
+20	I-GENE
+,	O
+a	O
+zinc	B-GENE
+finger	I-GENE
+gene	I-GENE
+,	O
+has	O
+a	O
+highly	O
+conserved	O
+pattern	O
+of	O
+expression	O
+in	O
+r3	O
+and	O
+r5	O
+and	O
+is	O
+functionally	O
+required	O
+for	O
+their	O
+maintenance	O
+in	O
+mouse	O
+embryos	O
+.	O
+
+Pituitary	O
+adenylate	B-GENE
+cyclase	I-GENE
+-	I-GENE
+activating	I-GENE
+polypeptide	I-GENE
+regulates	O
+prolactin	B-GENE
+promoter	I-GENE
+activity	O
+via	O
+a	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+-	O
+mediated	O
+pathway	O
+that	O
+is	O
+independent	O
+of	O
+the	O
+transcriptional	O
+pathway	O
+employed	O
+by	O
+thyrotropin	B-GENE
+-	I-GENE
+releasing	I-GENE
+hormone	I-GENE
+.	O
+
+Clones	O
+33F	O
+and	O
+34B	O
+encoded	O
+identical	O
+aromatase	B-GENE
+proteins	I-GENE
+of	O
+503	O
+amino	O
+acids	O
+,	O
+but	O
+differed	O
+in	O
+size	O
+due	O
+to	O
+alternative	O
+polyadenylation	O
+signal	O
+usage	O
+for	O
+the	O
+corresponding	O
+mRNAs	O
+.	O
+
+In	O
+sorted	O
+bone	O
+marrow	O
+cells	O
+expression	O
+of	O
+both	O
+VpreB	B-GENE
+genes	I-GENE
+was	O
+detected	O
+in	O
+pro	O
+-	O
+B	O
+/	O
+pre	O
+-	O
+BI	O
+and	O
+large	O
+pre	O
+-	O
+BII	O
+cells	O
+,	O
+while	O
+the	O
+RNA	O
+steady	O
+state	O
+levels	O
+were	O
+at	O
+least	O
+100	O
+-	O
+fold	O
+lower	O
+in	O
+small	O
+pre	O
+-	O
+BII	O
+and	O
+immature	O
+/	O
+mature	O
+B	O
+cells	O
+.	O
+
+We	O
+have	O
+cloned	O
+and	O
+sequenced	O
+a	O
+3574	O
+-	O
+bp	O
+Bacillus	O
+subtilis	O
+(	O
+Bs	O
+)	O
+DNA	O
+fragment	O
+located	O
+between	O
+the	O
+nrdA	B-GENE
+and	O
+citB	B-GENE
+genes	I-GENE
+at	O
+about	O
+169	O
+degrees	O
+on	O
+the	O
+chromosome	O
+.	O
+
+Aeromonas	O
+salmonicida	O
+possesses	O
+two	O
+genes	O
+encoding	O
+homologs	O
+of	O
+the	O
+major	B-GENE
+outer	I-GENE
+membrane	I-GENE
+protein	I-GENE
+,	O
+OmpA	B-GENE
+.	O
+
+Expression	O
+of	O
+Msp	B-GENE
+was	O
+toxic	O
+to	O
+E	O
+.	O
+coli	O
+when	O
+the	O
+entire	O
+msp	B-GENE
+gene	I-GENE
+was	O
+present	O
+.	O
+
+In	O
+agreement	O
+with	O
+previous	O
+in	O
+vitro	O
+data	O
+,	O
+we	O
+have	O
+shown	O
+that	O
+UmuD	B-GENE
+and	O
+UmuD	B-GENE
+'	I-GENE
+are	O
+able	O
+to	O
+form	O
+both	O
+homodimers	O
+(	O
+UmuD	B-GENE
+-	O
+UmuD	B-GENE
+and	O
+UmuD	B-GENE
+'	I-GENE
+-	O
+UmuD	B-GENE
+'	I-GENE
+)	O
+and	O
+a	O
+heterodimer	O
+(	O
+UmuD	B-GENE
+-	O
+UmuD	B-GENE
+'	I-GENE
+)	O
+.	O
+
+Lyn	B-GENE
+kinase	I-GENE
+immunoprecipitated	O
+from	O
+lysates	O
+of	O
+irradiated	O
+BCP	O
+as	O
+well	O
+as	O
+a	O
+full	O
+-	O
+length	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+(	O
+GST	B-GENE
+)	O
+-	O
+Lyn	B-GENE
+fusion	O
+protein	O
+-	O
+phosphorylated	O
+recombinant	B-GENE
+human	I-GENE
+p34cdc2	I-GENE
+on	O
+tyrosine	O
+15	O
+.	O
+
+Binding	O
+specificity	O
+and	O
+modulation	O
+of	O
+the	O
+ApoA	B-GENE
+-	I-GENE
+I	I-GENE
+promoter	I-GENE
+activity	O
+by	O
+homo	O
+-	O
+and	O
+heterodimers	O
+of	O
+nuclear	O
+receptors	O
+.	O
+
+There	O
+is	O
+growing	O
+evidence	O
+that	O
+mammalian	B-GENE
+AMP	I-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+AMPK	B-GENE
+)	O
+plays	O
+a	O
+role	O
+in	O
+protecting	O
+cells	O
+from	O
+stresses	O
+that	O
+cause	O
+ATP	O
+depletion	O
+by	O
+switching	O
+off	O
+ATP	O
+-	O
+consuming	O
+biosynthetic	O
+pathways	O
+.	O
+
+Sterol	O
+-	O
+mediated	O
+suppression	O
+of	O
+cleavage	O
+of	O
+SREBP	B-GENE
+-	I-GENE
+1	I-GENE
+was	O
+found	O
+to	O
+be	O
+dependent	O
+on	O
+the	O
+extreme	O
+COOH	O
+-	O
+terminal	O
+region	O
+(	O
+residue	O
+1034	O
+to	O
+the	O
+COOH	O
+terminus	O
+)	O
+,	O
+which	O
+exists	O
+in	O
+two	O
+forms	O
+as	O
+a	O
+result	O
+of	O
+alternative	O
+splicing	O
+.	O
+
+Am	O
+.	O
+
+EMSA	O
+competition	O
+experiments	O
+showed	O
+that	O
+mutations	O
+within	O
+the	O
+direct	O
+repeats	O
+failed	O
+to	O
+compete	O
+for	O
+binding	O
+of	O
+the	O
+nuclear	O
+proteins	O
+to	O
+labeled	O
+wild	O
+type	O
+oligonucleotide	O
+.	O
+
+Transcription	O
+from	O
+the	O
+promoter	O
+containing	O
+the	O
+mutated	O
+direct	O
+repeats	O
+was	O
+increased	O
+greatly	O
+,	O
+consistent	O
+with	O
+the	O
+conclusion	O
+that	O
+these	O
+motifs	O
+functions	O
+in	O
+vivo	O
+to	O
+repress	O
+GPT	B-GENE
+gene	I-GENE
+expression	O
+.	O
+
+However	O
+,	O
+a	O
+>	O
+10	O
+-	O
+fold	O
+increase	O
+in	O
+ERK3	B-GENE
+activity	O
+in	O
+each	O
+PKC	B-GENE
+beta	I-GENE
+transfectant	O
+was	O
+shown	O
+by	O
+immunoprecipitation	O
+with	O
+anti	B-GENE
+-	I-GENE
+ERK3	I-GENE
+monoclonal	I-GENE
+antibody	I-GENE
+followed	O
+by	O
+either	O
+immune	O
+complex	O
+kinase	O
+assay	O
+or	O
+by	O
+in	O
+gel	O
+kinase	O
+assay	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+this	O
+100	O
+-	O
+bp	O
+Col2a1	B-GENE
+enhancer	I-GENE
+revealed	O
+several	O
+sequence	O
+motifs	O
+similar	O
+to	O
+motifs	O
+present	O
+within	O
+the	O
+regulatory	O
+region	O
+of	O
+the	O
+link	B-GENE
+protein	I-GENE
+gene	I-GENE
+,	O
+another	O
+cartilage	O
+gene	O
+.	O
+
+Retinoid	O
+-	O
+dependent	O
+activation	O
+of	O
+the	O
+tissue	B-GENE
+transglutaminase	I-GENE
+promoter	I-GENE
+depends	O
+on	O
+both	O
+a	O
+proximal	O
+regulatory	O
+region	O
+containing	O
+sequences	O
+highly	O
+conserved	O
+between	O
+the	O
+human	O
+and	O
+the	O
+mouse	B-GENE
+tissue	I-GENE
+transglutaminase	I-GENE
+promoters	I-GENE
+and	O
+a	O
+distal	O
+region	O
+that	O
+includes	O
+a	O
+30	O
+-	O
+base	O
+pair	O
+retinoid	O
+response	O
+element	O
+(	O
+mTGRRE1	O
+)	O
+.	O
+mTGRRE1	O
+contains	O
+three	O
+hexanucleotide	O
+half	O
+-	O
+sites	O
+(	O
+two	O
+canonical	O
+and	O
+one	O
+non	O
+-	O
+canonical	O
+)	O
+in	O
+a	O
+DR7	B-GENE
+/	O
+DR5	B-GENE
+motif	O
+that	O
+bind	O
+both	O
+RAR	B-GENE
+*	O
+RXR	B-GENE
+heterodimers	O
+and	O
+RXR	B-GENE
+homodimers	I-GENE
+.	O
+
+Significantly	O
+,	O
+pPKR	B-GENE
+is	O
+capable	O
+of	O
+specifically	O
+phosphorylating	O
+Ser51	O
+in	O
+a	O
+synthetic	B-GENE
+eIF	I-GENE
+-	I-GENE
+2alpha	I-GENE
+peptide	I-GENE
+,	O
+a	O
+key	O
+characteristic	O
+of	O
+the	O
+eIF	B-GENE
+-	I-GENE
+2alpha	I-GENE
+kinase	I-GENE
+family	I-GENE
+.	O
+
+Vertebrate	B-GENE
+synapsins	I-GENE
+constitute	O
+a	O
+family	O
+of	O
+synaptic	O
+proteins	O
+that	O
+participate	O
+in	O
+the	O
+regulation	O
+of	O
+neurotransmitter	O
+release	O
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+using	O
+crude	O
+extracts	O
+from	O
+FREJ4	O
+cells	O
+revealed	O
+the	O
+binding	O
+of	O
+a	O
+member	O
+(	O
+s	O
+)	O
+of	O
+the	O
+Ets	B-GENE
+family	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+to	O
+the	O
+P4	B-GENE
+EBS	I-GENE
+,	O
+as	O
+well	O
+as	O
+the	O
+interaction	O
+of	O
+two	O
+members	O
+of	O
+the	O
+Sp1	B-GENE
+family	I-GENE
+,	O
+Sp1	B-GENE
+and	O
+Sp3	B-GENE
+,	O
+with	O
+the	O
+adjacent	O
+GC	O
+box	O
+.	O
+
+ZEBRA	B-GENE
+and	O
+cellular	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+bZip	I-GENE
+activators	I-GENE
+,	O
+such	O
+as	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+,	O
+have	O
+homologous	O
+DNA	O
+-	O
+binding	O
+domains	O
+,	O
+and	O
+their	O
+DNA	O
+-	O
+binding	O
+specificities	O
+overlap	O
+.	O
+
+This	O
+result	O
+suggested	O
+that	O
+mutant	O
+I299	O
+has	O
+diminished	O
+cap	O
+-	O
+binding	O
+activity	O
+.	O
+
+UV	O
+cross	O
+-	O
+linking	O
+experiments	O
+demonstrated	O
+that	O
+HSV	O
+infection	O
+caused	O
+enhanced	O
+binding	O
+of	O
+protein	O
+factors	O
+,	O
+including	O
+the	O
+64	B-GENE
+-	I-GENE
+kDa	I-GENE
+component	I-GENE
+of	I-GENE
+cleavage	I-GENE
+stimulation	I-GENE
+factor	I-GENE
+(	O
+CstF	B-GENE
+)	O
+,	O
+to	O
+poly	O
+(	O
+A	O
+)	O
+site	O
+RNAs	O
+from	O
+virus	O
+genes	O
+of	O
+all	O
+temporal	O
+classes	O
+and	O
+that	O
+this	O
+enhanced	O
+binding	O
+required	O
+expression	O
+of	O
+IE63	B-GENE
+.	O
+
+CM	B-GENE
+-	I-GENE
+ACO3	I-GENE
+is	O
+expressed	O
+in	O
+flowers	O
+and	O
+is	O
+not	O
+induced	O
+by	O
+any	O
+of	O
+the	O
+stimuli	O
+tested	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+these	O
+Jun	B-GENE
+/	O
+eb1	B-GENE
+chimeras	O
+are	O
+potent	O
+transactivators	O
+of	O
+AP1	B-GENE
+sites	I-GENE
+and	O
+that	O
+they	O
+can	O
+cooperate	O
+with	O
+c	B-GENE
+-	I-GENE
+Ha	I-GENE
+-	I-GENE
+Ras	I-GENE
+to	O
+induce	O
+foci	O
+.	O
+
+In	O
+synchronized	O
+HeLa	O
+cells	O
+,	O
+expression	O
+of	O
+luciferase	B-GENE
+activity	O
+was	O
+induced	O
+at	O
+the	O
+beginning	O
+of	O
+DNA	O
+synthesis	O
+and	O
+was	O
+dependent	O
+on	O
+the	O
+presence	O
+of	O
+an	O
+E2F	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+in	O
+the	O
+H2A	B-GENE
+.	I-GENE
+1	I-GENE
+promoter	I-GENE
+.	O
+
+Utilizing	O
+transient	O
+transfection	O
+studies	O
+in	O
+HepG2	O
+cells	O
+,	O
+we	O
+have	O
+shown	O
+that	O
+deletion	O
+of	O
+the	O
+factor	B-GENE
+VIII	I-GENE
+promoter	I-GENE
+sequences	I-GENE
+distal	O
+to	O
+nucleotide	O
+-	O
+44	O
+results	O
+in	O
+a	O
+significant	O
+but	O
+small	O
+increase	O
+in	O
+promoter	O
+activity	O
+.	O
+
+We	O
+constructed	O
+a	O
+yeast	O
+reporter	O
+strain	O
+containing	O
+the	O
+lacZ	B-GENE
+gene	I-GENE
+under	O
+the	O
+control	O
+of	O
+the	O
+CYC1	B-GENE
+promoter	I-GENE
+associated	O
+with	O
+three	O
+copies	O
+of	O
+TRE	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+If	O
+hnRNP	B-GENE
+K	I-GENE
+is	O
+a	O
+transcription	O
+factor	O
+,	O
+then	O
+interactions	O
+with	O
+the	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+transcription	O
+apparatus	O
+are	O
+predicted	O
+.	O
+
+A	O
+developmentally	O
+regulated	O
+4	O
+.	O
+6	O
+kb	O
+mRNA	O
+is	O
+recognized	O
+on	O
+Northern	O
+blots	O
+of	O
+oocyte	O
+RNA	O
+using	O
+the	O
+X	O
+.	O
+laevis	O
+cDNA	O
+.	O
+
+Sequence	O
+conservation	O
+is	O
+greatest	O
+for	O
+residues	O
+located	O
+near	O
+the	O
+active	O
+centers	O
+of	O
+the	O
+exo	B-GENE
+and	O
+pol	B-GENE
+domains	I-GENE
+of	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+DNA	I-GENE
+polymerase	I-GENE
+I	I-GENE
+structure	O
+.	O
+
+Despite	O
+the	O
+favourable	O
+natural	O
+history	O
+of	O
+acute	O
+BI	O
+,	O
+mild	O
+,	O
+moderate	O
+,	O
+and	O
+severe	O
+posttraumatic	O
+changes	O
+were	O
+shown	O
+to	O
+appear	O
+as	O
+cicatricial	O
+-	O
+adhesive	O
+and	O
+atrophic	O
+processes	O
+,	O
+intracerebral	O
+cysts	O
+,	O
+porencephaly	O
+,	O
+which	O
+result	O
+in	O
+posttraumatic	O
+epilepsy	O
+,	O
+hydrocephalus	O
+,	O
+etc	O
+.	O
+
+Several	O
+cytokines	O
+exhibit	O
+a	O
+high	O
+degree	O
+of	O
+temporal	O
+regulation	O
+as	O
+well	O
+as	O
+somnogenic	O
+potency	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+[	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+]	O
+,	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+[	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+]	O
+)	O
+.	O
+
+As	O
+pH	O
+and	O
+Hb	B-GENE
+can	O
+also	O
+affect	O
+mixed	O
+venous	O
+CO2	O
+content	O
+,	O
+the	O
+effect	O
+on	O
+Q	O
+was	O
+also	O
+assessed	O
+.	O
+
+No	O
+difference	O
+in	O
+elastin	B-GENE
+peptide	I-GENE
+concentration	O
+was	O
+observed	O
+between	O
+emphysematous	O
+patients	O
+and	O
+control	O
+subjects	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+=	O
+2	O
+.	O
+39	O
++	O
+/	O
+-	O
+1	O
+.	O
+18	O
+micrograms	O
+/	O
+ml	O
+in	O
+patients	O
+versus	O
+2	O
+.	O
+55	O
++	O
+/	O
+-	O
+1	O
+.	O
+34	O
+micrograms	O
+/	O
+ml	O
+in	O
+policemen	O
+and	O
+2	O
+.	O
+59	O
++	O
+/	O
+-	O
+1	O
+.	O
+20	O
+micrograms	O
+/	O
+ml	O
+in	O
+coal	O
+miners	O
+)	O
+.	O
+
+Identification	O
+of	O
+this	O
+region	O
+as	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+tmk	I-GENE
+gene	I-GENE
+was	O
+confirmed	O
+by	O
+functional	O
+complementation	O
+of	O
+a	O
+yeast	B-GENE
+dTMP	I-GENE
+kinase	I-GENE
+temperature	O
+-	O
+sensitive	O
+mutant	O
+and	O
+by	O
+in	O
+vitro	O
+enzyme	O
+assay	O
+of	O
+the	O
+thymidylate	B-GENE
+kinase	I-GENE
+activity	O
+in	O
+cell	O
+extracts	O
+of	O
+E	O
+.	O
+coli	O
+by	O
+use	O
+of	O
+tmk	B-GENE
+-	O
+overproducing	O
+plasmids	O
+.	O
+
+The	O
+structural	O
+gene	O
+for	O
+copper	B-GENE
+-	I-GENE
+and	I-GENE
+topa	I-GENE
+quinone	I-GENE
+-	I-GENE
+containing	I-GENE
+monoamine	I-GENE
+oxidase	I-GENE
+(	O
+maoA	B-GENE
+)	O
+and	O
+an	O
+unknown	O
+amine	B-GENE
+oxidase	I-GENE
+gene	I-GENE
+have	O
+been	O
+located	O
+at	O
+30	O
+.	O
+9	O
+min	O
+on	O
+the	O
+Escherichia	O
+coli	O
+chromosome	O
+.	O
+
+This	O
+interaction	O
+is	O
+mediated	O
+by	O
+the	O
+SH2	B-GENE
+domain	I-GENE
+of	O
+Crk	B-GENE
+and	O
+can	O
+be	O
+inhibited	O
+with	O
+a	O
+phosphopeptide	O
+containing	O
+the	O
+Crk	B-GENE
+-	O
+SH2	B-GENE
+binding	O
+motif	O
+.	O
+
+The	O
+cDNA	O
+corresponding	O
+to	O
+the	O
+FPS1	B-GENE
+gene	I-GENE
+was	O
+isolated	O
+by	O
+functional	O
+complementation	O
+of	O
+a	O
+mutant	O
+yeast	O
+strain	O
+defective	O
+in	O
+FPS	B-GENE
+activity	O
+(	O
+Delourme	O
+,	O
+D	O
+.	O
+,	O
+Lacroute	O
+,	O
+F	O
+.	O
+,	O
+and	O
+Karst	O
+,	O
+F	O
+.	O
+
+The	O
+isolated	O
+plasmin	B-GENE
+fragments	O
+of	O
+VEGF	B-GENE
+were	O
+compared	O
+with	O
+respect	O
+to	O
+heparin	O
+binding	O
+,	O
+interaction	O
+with	O
+soluble	O
+VEGF	B-GENE
+receptors	I-GENE
+,	O
+and	O
+ability	O
+to	O
+promote	O
+endothelial	O
+cell	O
+mitogenesis	O
+.	O
+
+The	O
+members	O
+of	O
+the	O
+Myb	B-GENE
+family	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+are	O
+defined	O
+by	O
+homology	O
+in	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+;	O
+all	O
+bind	O
+the	O
+Myb	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+(	O
+MBS	B-GENE
+)	O
+sequence	O
+(	O
+YG	O
+(	O
+A	O
+/	O
+G	O
+)	O
+C	O
+(	O
+A	O
+/	O
+C	O
+/	O
+G	O
+)	O
+GTT	O
+(	O
+G	O
+/	O
+A	O
+)	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+when	O
+the	O
+isoform	O
+containing	O
+the	O
+C	O
+epsilon4	O
+domain	O
+joined	O
+directly	O
+to	O
+the	O
+M2	O
+exon	O
+(	O
+IgE	B-GENE
+grande	I-GENE
+)	O
+is	O
+expressed	O
+in	O
+the	O
+J558L	O
+cell	O
+line	O
+,	O
+it	O
+is	O
+degraded	O
+intracellularly	O
+,	O
+suggesting	O
+a	O
+cell	O
+line	O
+-	O
+dependent	O
+regulation	O
+of	O
+secretion	O
+.	O
+
+Human	B-GENE
+cytomegalovirus	I-GENE
+immediate	I-GENE
+-	I-GENE
+early	I-GENE
+protein	I-GENE
+IE2	I-GENE
+tethers	O
+a	O
+transcriptional	O
+repression	O
+domain	O
+to	O
+p53	B-GENE
+.	O
+
+The	O
+specificity	O
+of	O
+action	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+family	I-GENE
+members	I-GENE
+may	O
+be	O
+derived	O
+from	O
+the	O
+characteristics	O
+of	O
+each	O
+factor	O
+,	O
+including	O
+the	O
+expression	O
+profiles	O
+,	O
+the	O
+DNA	O
+binding	O
+affinities	O
+,	O
+the	O
+cofactors	O
+,	O
+and	O
+so	O
+on	O
+,	O
+in	O
+addition	O
+to	O
+the	O
+DNA	O
+binding	O
+specificities	O
+.	O
+
+The	O
+antibodies	O
+inhibited	O
+specifically	O
+the	O
+transcription	O
+of	O
+DNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+promoter	O
+in	O
+vitro	O
+.	O
+
+Immunocytochemical	O
+analysis	O
+demonstrated	O
+the	O
+presence	O
+of	O
+DREF	B-GENE
+polypeptide	I-GENE
+in	O
+nuclei	O
+after	O
+the	O
+eighth	O
+nuclear	O
+division	O
+cycle	O
+,	O
+suggesting	O
+that	O
+nuclear	O
+accumulation	O
+of	O
+DREF	B-GENE
+is	O
+important	O
+for	O
+the	O
+coordinate	O
+zygotic	O
+expression	O
+of	O
+DNA	O
+replication	O
+-	O
+related	O
+genes	O
+carrying	O
+DRE	O
+sequences	O
+.	O
+
+A	O
+DNA	O
+fragment	O
+carrying	O
+1	O
+,	O
+100	O
+nucleotides	O
+derived	O
+from	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+UGT1A1	B-GENE
+gene	I-GENE
+was	O
+enough	O
+for	O
+MC	O
+induction	O
+.	O
+
+This	O
+result	O
+supports	O
+the	O
+argument	O
+that	O
+the	O
+beta	O
+'	O
+subunit	O
+plays	O
+an	O
+essential	O
+role	O
+in	O
+determining	O
+the	O
+progress	O
+of	O
+transcription	O
+elongation	O
+.	O
+
+Two	O
+XPG	B-GENE
+regions	I-GENE
+with	O
+putative	O
+NLS	O
+[	O
+amino	O
+acid	O
+(	O
+AA	O
+)	O
+coordinates	O
+:	O
+NLS	O
+-	O
+B	O
+(	O
+AA	O
+1057	O
+-	O
+1074	O
+)	O
+and	O
+NLS	O
+-	O
+C	O
+(	O
+AA	O
+1171	O
+-	O
+1185	O
+)	O
+]	O
+were	O
+each	O
+shown	O
+to	O
+independently	O
+localize	O
+the	O
+beta	B-GENE
+-	I-GENE
+gal	I-GENE
+extensively	O
+(	O
+>	O
+80	O
+%	O
+)	O
+to	O
+the	O
+nucleus	O
+of	O
+HeLa	O
+cells	O
+.	O
+
+The	O
+lacS	B-GENE
+gene	I-GENE
+was	O
+cloned	O
+in	O
+an	O
+E	O
+.	O
+coli	O
+-	O
+Streptococcus	O
+shuttle	O
+vector	O
+and	O
+was	O
+expressed	O
+both	O
+in	O
+a	O
+lacS	B-GENE
+deletion	O
+derivative	O
+of	O
+S	O
+.	O
+thermophilus	O
+and	O
+in	O
+a	O
+pNZ63	O
+-	O
+cured	O
+strain	O
+,	O
+L	O
+.	O
+lactis	O
+NZ6091	O
+.	O
+
+The	O
+genome	O
+of	O
+all	O
+retroviruses	O
+consists	O
+of	O
+two	O
+identical	O
+RNAs	O
+noncovalently	O
+linked	O
+near	O
+their	O
+5	O
+'	O
+end	O
+.	O
+
+The	O
+extraction	O
+recovery	O
+of	O
+Amphotericin	O
+B	O
+from	O
+the	O
+cerebrospinal	O
+fluid	O
+is	O
+higher	O
+than	O
+90	O
+%	O
+over	O
+the	O
+entire	O
+linear	O
+range	O
+.	O
+
+HuEpo	B-GENE
+-	I-GENE
+R	I-GENE
+Ab	I-GENE
+inhibited	O
+Epo	B-GENE
+-	O
+induced	O
+parental	O
+UT	O
+-	O
+7	O
+cell	O
+growth	O
+,	O
+but	O
+not	O
+that	O
+of	O
+cells	O
+of	O
+clone	O
+12	O
+,	O
+suggesting	O
+that	O
+the	O
+muEpo	B-GENE
+-	I-GENE
+R	I-GENE
+is	O
+able	O
+to	O
+induce	O
+human	O
+UT	O
+-	O
+7	O
+cell	O
+proliferation	O
+.	O
+
+The	O
+frequency	O
+of	O
+integrations	O
+that	O
+led	O
+to	O
+transcription	O
+of	O
+the	O
+lacZ	B-GENE
+gene	I-GENE
+was	O
+estimated	O
+to	O
+be	O
+0	O
+.	O
+5	O
+%	O
+of	O
+all	O
+integrations	O
+,	O
+of	O
+which	O
+14	O
+%	O
+were	O
+downregulated	O
+on	O
+differentiation	O
+of	O
+32D	O
+cells	O
+towards	O
+neutrophils	O
+.	O
+
+Interaction	O
+of	O
+the	O
+Fur	B-GENE
+repressor	I-GENE
+with	O
+a	O
+150	O
+-	O
+bp	O
+fragment	O
+encompassing	O
+the	O
+pvdS	B-GENE
+promoter	I-GENE
+was	O
+demonstrated	O
+in	O
+vivo	O
+by	O
+the	O
+Fur	B-GENE
+titration	O
+assay	O
+and	O
+confirmed	O
+in	O
+vitro	O
+by	O
+gel	O
+retardation	O
+experiments	O
+with	O
+a	O
+partially	O
+purified	O
+Fur	B-GENE
+preparation	O
+.	O
+
+This	O
+protein	O
+encoded	O
+by	O
+this	O
+cDNA	O
+,	O
+which	O
+we	O
+have	O
+termed	O
+p150TSP	B-GENE
+(	O
+for	O
+TPR	O
+-	O
+containing	O
+,	O
+SH2	B-GENE
+-	I-GENE
+binding	I-GENE
+phosphoprotein	I-GENE
+)	O
+,	O
+is	O
+located	O
+predominantly	O
+in	O
+the	O
+nucleus	O
+and	O
+is	O
+highly	O
+conserved	O
+in	O
+evolution	O
+.	O
+
+Both	O
+mutant	O
+receptors	O
+were	O
+expressed	O
+on	O
+the	O
+cell	O
+surface	O
+and	O
+bound	O
+insulin	B-GENE
+normally	O
+,	O
+but	O
+showed	O
+markedly	O
+impaired	O
+autophosphorylation	O
+in	O
+response	O
+to	O
+insulin	B-GENE
+.	O
+
+EMBO	O
+J	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+results	O
+indicate	O
+that	O
+thrombin	B-GENE
+-	O
+stimulated	O
+vascular	O
+smooth	O
+muscle	O
+proliferation	O
+is	O
+delayed	O
+and	O
+requires	O
+the	O
+de	O
+novo	O
+expression	O
+of	O
+one	O
+or	O
+more	O
+autocrine	O
+mitogens	O
+.	O
+
+Transcription	O
+from	O
+adenovirus	B-GENE
+E2	I-GENE
+-	I-GENE
+early	I-GENE
+promoter	I-GENE
+is	O
+controlled	O
+by	O
+a	O
+unique	O
+array	O
+of	O
+four	O
+cis	O
+-	O
+acting	O
+elements	O
+which	O
+include	O
+an	O
+atypical	O
+TBP	B-GENE
+site	I-GENE
+,	O
+two	O
+E2F	B-GENE
+sites	I-GENE
+present	O
+in	O
+an	O
+inverted	O
+orientation	O
+relative	O
+to	O
+each	O
+other	O
+,	O
+and	O
+an	O
+ATF	B-GENE
+site	I-GENE
+.	O
+
+Furthermore	O
+,	O
+we	O
+showed	O
+that	O
+the	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+/	O
+interferon	B-GENE
+gamma	I-GENE
+(	O
+IFN	B-GENE
+gamma	I-GENE
+)	O
+response	O
+element	O
+in	O
+the	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+(	O
+IR	B-GENE
+/	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+which	O
+contains	O
+a	O
+Stat	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+and	O
+an	O
+adjacent	O
+CRE	O
+-	O
+like	O
+site	O
+,	O
+also	O
+makes	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+-	O
+induced	O
+binding	O
+complexes	O
+similar	O
+to	O
+JRE	O
+-	O
+IL6	B-GENE
+-	O
+BCs	O
+.	O
+
+A	O
+second	O
+peptide	O
+(	O
+amino	O
+acids	O
+58	O
+-	O
+77	O
+)	O
+also	O
+antagonized	O
+p21	B-GENE
+-	O
+activity	O
+,	O
+but	O
+this	O
+peptide	O
+did	O
+not	O
+affect	O
+the	O
+ability	O
+of	O
+p21	B-GENE
+to	O
+interact	O
+with	O
+cyclin	B-GENE
+E	I-GENE
+/	O
+Cdk2	B-GENE
+.	O
+
+A	O
+p21	B-GENE
+peptide	I-GENE
+spanning	O
+amino	O
+acids	O
+139	O
+-	O
+164	O
+was	O
+found	O
+to	O
+bind	O
+PCNA	B-GENE
+in	O
+a	O
+filter	O
+binding	O
+assay	O
+and	O
+this	O
+peptide	O
+suppressed	O
+recombinant	O
+p21	B-GENE
+-	O
+PCNA	B-GENE
+interaction	O
+.	O
+
+Results	O
+were	O
+supported	O
+by	O
+the	O
+agar	O
+diffusion	O
+method	O
+for	O
+Y	O
+.	O
+enterocolitica	O
+,	O
+whereas	O
+inhibition	O
+activity	O
+was	O
+not	O
+found	O
+for	O
+A	O
+.	O
+hydrophila	O
+.	O
+
+OND	O
+8	O
+mg	O
+tid	O
+days	O
+2	O
+-	O
+3	O
+,	O
+and	O
+8	O
+mg	O
+tid	O
+prn	O
+days	O
+4	O
+-	O
+5	O
+and	O
+prednisolone	O
+75	O
+-	O
+100	O
+mg	O
+qds	O
+days	O
+2	O
+-	O
+5	O
+and	O
+2	O
+)	O
+MCP	O
+30	O
+mg	O
+/	O
+metylprednisolone	O
+80	O
+mg	O
+i	O
+.	O
+v	O
+.	O
+before	O
+CT	O
+and	O
+MCP	O
+20	O
+mg	O
+p	O
+.	O
+r	O
+.	O
+after	O
+4	O
+and	O
+8	O
+h	O
+respectively	O
+.	O
+
+The	O
+dynamic	O
+properties	O
+of	O
+this	O
+protein	O
+fragment	O
+were	O
+measured	O
+and	O
+analyzed	O
+using	O
+both	O
+isotropic	O
+and	O
+anisotropic	O
+models	O
+of	O
+molecular	O
+motion	O
+.	O
+
+Adduction	O
+of	O
+the	O
+human	B-GENE
+N	I-GENE
+-	I-GENE
+ras	I-GENE
+codon	I-GENE
+61	I-GENE
+sequence	I-GENE
+with	O
+(	O
+-	O
+)	O
+-	O
+(	O
+7S	O
+,	O
+8R	O
+,	O
+9R	O
+,	O
+10S	O
+)	O
+-	O
+7	O
+,	O
+8	O
+-	O
+dihydroxy	O
+-	O
+9	O
+,	O
+10	O
+-	O
+epoxy	O
+-	O
+7	O
+,	O
+8	O
+,	O
+9	O
+,	O
+10	O
+-	O
+tetrahydrobenzo	O
+[	O
+a	O
+]	O
+pyrene	O
+:	O
+structural	O
+refinement	O
+of	O
+the	O
+intercalated	O
+SRSR	O
+(	O
+61	O
+,	O
+2	O
+)	O
+(	O
+-	O
+)	O
+-	O
+(	O
+7S	O
+,	O
+8R	O
+,	O
+9S	O
+,	O
+10R	O
+)	O
+-	O
+N6	O
+-	O
+[	O
+10	O
+-	O
+(	O
+7	O
+,	O
+8	O
+,	O
+9	O
+,	O
+10	O
+-	O
+tetrahydrobenzo	O
+[	O
+a	O
+]	O
+pyrenyl	O
+)	O
+]	O
+-	O
+2	O
+'	O
+-	O
+deoxyadenosyl	O
+adduct	O
+from	O
+1H	O
+NMR	O
+.	O
+
+This	O
+fragment	O
+can	O
+bind	O
+several	O
+trans	O
+-	O
+acting	O
+factors	O
+in	O
+vitro	O
+,	O
+including	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+members	O
+of	O
+the	O
+Ets	B-GENE
+family	I-GENE
+.	O
+
+These	O
+different	O
+observations	O
+exclude	O
+a	O
+heterozygosity	O
+of	O
+the	O
+A	O
+-	O
+-	O
+>	O
+G	O
+mutation	O
+at	O
+codon	O
+beta	O
+77	O
+,	O
+as	O
+well	O
+as	O
+a	O
+deletion	O
+comparable	O
+to	O
+that	O
+of	O
+Hbs	B-GENE
+Lepore	I-GENE
+or	I-GENE
+Kenya	I-GENE
+,	O
+or	O
+a	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+gene	I-GENE
+duplication	O
+,	O
+and	O
+point	O
+to	O
+a	O
+nontraditional	O
+inheritance	O
+of	O
+Hb	B-GENE
+Costa	I-GENE
+Rica	I-GENE
+.	O
+
+This	O
+is	O
+the	O
+first	O
+description	O
+,	O
+to	O
+our	O
+knowledge	O
+,	O
+of	O
+regulatory	O
+elements	O
+that	O
+control	O
+expression	O
+of	O
+a	O
+gene	O
+encoding	O
+a	O
+B7	B-GENE
+costimulatory	I-GENE
+molecule	I-GENE
+.	O
+
+DNA	B-GENE
+-	I-GENE
+STAT	I-GENE
+complexes	I-GENE
+were	O
+detected	O
+in	O
+all	O
+Bcr	B-GENE
+/	O
+Abl	B-GENE
+-	O
+transformed	O
+cell	O
+lines	O
+and	O
+they	O
+were	O
+supershifted	O
+by	O
+antibodies	O
+against	O
+STAT1	B-GENE
+and	O
+STAT5	B-GENE
+.	O
+
+When	O
+overexpressed	O
+in	O
+an	O
+appropriate	O
+cell	O
+line	O
+,	O
+TAN	B-GENE
+-	I-GENE
+1C	I-GENE
+prevented	O
+kappa	B-GENE
+B	I-GENE
+-	O
+dependent	O
+transactivation	O
+in	O
+transient	O
+reporter	O
+gene	O
+assays	O
+in	O
+a	O
+fashion	O
+similar	O
+to	O
+the	O
+structurally	O
+related	O
+protein	O
+,	O
+Bcl	B-GENE
+-	I-GENE
+3	I-GENE
+.	O
+
+T	O
+cell	O
+leukemia	O
+-	O
+associated	O
+human	O
+Notch	B-GENE
+/	O
+translocation	O
+-	O
+associated	O
+Notch	B-GENE
+homologue	O
+has	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+-	O
+like	O
+activity	O
+and	O
+physically	O
+interacts	O
+with	O
+nuclear	B-GENE
+factor	I-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+proteins	O
+in	O
+T	O
+cells	O
+.	O
+
+Polyprotein	O
+processing	O
+in	O
+Southampton	O
+virus	O
+:	O
+identification	O
+of	O
+3C	B-GENE
+-	I-GENE
+like	I-GENE
+protease	I-GENE
+cleavage	O
+sites	O
+by	O
+in	O
+vitro	O
+mutagenesis	O
+.	O
+
+The	O
+humanized	B-GENE
+LL2	I-GENE
+(	O
+hLL2	B-GENE
+)	O
+,	O
+lacking	O
+light	B-GENE
+chain	I-GENE
+variable	I-GENE
+region	I-GENE
+glycosylation	O
+,	O
+exhibited	O
+immunoreactivities	O
+that	O
+were	O
+comparable	O
+to	O
+that	O
+of	O
+chimeric	B-GENE
+LL2	I-GENE
+(	O
+cLL2	B-GENE
+)	O
+,	O
+which	O
+was	O
+shown	O
+previously	O
+to	O
+have	O
+antigen	O
+-	O
+binding	O
+properties	O
+similar	O
+to	O
+its	O
+murine	O
+counterpart	O
+,	O
+suggesting	O
+that	O
+the	O
+VK	O
+-	O
+appended	O
+oligosaccharides	O
+found	O
+in	O
+mLL2	B-GENE
+are	O
+not	O
+necessary	O
+for	O
+antigen	O
+binding	O
+.	O
+
+An	O
+apparent	O
+N	O
+-	O
+terminal	O
+transit	O
+peptide	O
+in	O
+the	O
+coding	O
+region	O
+and	O
+a	O
+3	O
+'	O
+poly	O
+(	O
+A	O
+)	O
+tail	O
+exist	O
+in	O
+the	O
+cDNA	O
+clone	O
+indicated	O
+that	O
+this	O
+chloroplast	O
+protein	O
+as	O
+nuclear	O
+encoded	O
+.	O
+
+Thus	O
+,	O
+a	O
+critical	O
+question	O
+is	O
+how	O
+HOX	B-GENE
+proteins	I-GENE
+select	O
+the	O
+correct	O
+sets	O
+of	O
+target	O
+genes	O
+in	O
+vivo	O
+.	O
+
+RAS2val19	B-GENE
+,	O
+a	O
+dominant	O
+activated	O
+form	O
+of	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+Ras2	I-GENE
+,	O
+stimulates	O
+both	O
+filamentous	O
+growth	O
+and	O
+expression	O
+of	O
+a	O
+transcriptional	O
+reporter	O
+FG	B-GENE
+(	O
+TyA	B-GENE
+)	O
+:	O
+:	O
+lacZ	B-GENE
+but	O
+does	O
+not	O
+induce	O
+the	O
+mating	B-GENE
+pathway	I-GENE
+reporter	I-GENE
+FUS1	I-GENE
+:	O
+:	O
+lacZ	B-GENE
+.	O
+
+Moreover	O
+,	O
+the	O
+Rho	B-GENE
+family	I-GENE
+protein	I-GENE
+Cdc42	B-GENE
+,	O
+a	O
+conserved	O
+morphogenetic	B-GENE
+G	I-GENE
+protein	I-GENE
+,	O
+is	O
+also	O
+a	O
+potent	O
+regulator	O
+of	O
+filamentous	O
+growth	O
+and	O
+FG	B-GENE
+(	O
+TyA	B-GENE
+)	O
+:	O
+:	O
+lacZ	B-GENE
+expression	O
+in	O
+S	O
+.	O
+cerevisiae	O
+.	O
+
+Each	O
+immunoprecipitate	O
+contained	O
+a	O
+complex	O
+of	O
+N1	B-GENE
+(	I-GENE
+deltaEC	I-GENE
+)	I-GENE
+and	O
+CBF1	B-GENE
+.	O
+
+This	O
+region	O
+includes	O
+verA	B-GENE
+,	O
+a	O
+structural	O
+gene	O
+previously	O
+shown	O
+to	O
+be	O
+required	O
+for	O
+ST	O
+biosynthesis	O
+,	O
+and	O
+24	O
+additional	O
+closely	O
+spaced	O
+transcripts	O
+ranging	O
+in	O
+size	O
+from	O
+0	O
+.	O
+6	O
+to	O
+7	O
+.	O
+2	O
+kb	O
+that	O
+are	O
+coordinately	O
+induced	O
+only	O
+under	O
+ST	O
+-	O
+producing	O
+conditions	O
+.	O
+
+Subcellular	O
+localizations	O
+of	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+CBFbeta	I-GENE
+and	O
+the	O
+CBFbeta	B-GENE
+-	O
+SMMHC	B-GENE
+fusion	O
+protein	O
+were	O
+determined	O
+by	O
+immunofluorescence	O
+of	O
+NIH	O
+3T3	O
+cells	O
+that	O
+overexpress	O
+wild	O
+-	O
+type	O
+or	O
+fusion	O
+protein	O
+.	O
+
+Menstrual	O
+-	O
+cycle	O
+phase	O
+did	O
+not	O
+significantly	O
+affect	O
+personality	O
+variables	O
+in	O
+either	O
+group	O
+.	O
+
+We	O
+report	O
+the	O
+isolation	O
+of	O
+human	O
+cDNAs	O
+homologous	O
+to	O
+the	O
+Drosophila	B-GENE
+dishevelled	I-GENE
+(	O
+dsh	B-GENE
+)	O
+segment	O
+-	O
+polarity	O
+gene	O
+.	O
+
+Ca2	O
++	O
+decreased	O
+Zn2	O
++	O
+binding	O
+in	O
+S100	B-GENE
+beta	I-GENE
+but	O
+it	O
+did	O
+not	O
+influence	O
+binding	O
+to	O
+MRP14	B-GENE
+,	O
+suggesting	O
+that	O
+the	O
+Zn2	O
++	O
+binding	O
+site	O
+was	O
+distinct	O
+from	O
+and	O
+independent	O
+of	O
+the	O
+two	O
+Ca2	O
++	O
+binding	O
+domains	O
+.	O
+
+Two	O
+overlapping	O
+clones	O
+contained	O
+the	O
+complete	O
+Adh	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+composed	O
+of	O
+nine	O
+exons	O
+in	O
+a	O
+12	O
+-	O
+kb	O
+region	O
+,	O
+with	O
+the	O
+placement	O
+of	O
+introns	O
+matching	O
+that	O
+observed	O
+in	O
+other	O
+mammalian	B-GENE
+ADH	I-GENE
+genes	I-GENE
+.	O
+
+Ligation	O
+of	O
+CD40	B-GENE
+rescues	O
+Ramos	O
+-	O
+Burkitt	O
+lymphoma	O
+B	O
+cells	O
+from	O
+calcium	O
+ionophore	O
+-	O
+and	O
+antigen	O
+receptor	O
+-	O
+triggered	O
+apoptosis	O
+by	O
+inhibiting	O
+activation	O
+of	O
+the	O
+cysteine	B-GENE
+protease	I-GENE
+CPP32	B-GENE
+/	O
+Yama	B-GENE
+and	O
+cleavage	O
+of	O
+its	O
+substrate	O
+PARP	B-GENE
+.	O
+
+Large	B-GENE
+T	I-GENE
+antigen	I-GENE
+was	O
+coimmunoprecipitated	O
+by	O
+antibodies	O
+to	O
+epitope	O
+-	O
+tagged	O
+TBP	B-GENE
+,	O
+endogenous	O
+TBP	B-GENE
+,	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+100	I-GENE
+,	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+130	I-GENE
+,	O
+and	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+250	I-GENE
+,	O
+under	O
+conditions	O
+where	O
+holo	B-GENE
+-	I-GENE
+TFIID	I-GENE
+would	O
+be	O
+precipitated	O
+.	O
+
+Northern	O
+blot	O
+hybridization	O
+demonstrated	O
+that	O
+HEP	B-GENE
+-	O
+COP	B-GENE
+was	O
+expressed	O
+in	O
+a	O
+wide	O
+range	O
+of	O
+human	O
+adult	O
+and	O
+fetal	O
+tissues	O
+.	O
+
+A	O
+direct	O
+role	O
+for	O
+sterol	B-GENE
+regulatory	I-GENE
+element	I-GENE
+binding	I-GENE
+protein	I-GENE
+in	O
+activation	O
+of	O
+3	B-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+methylglutaryl	I-GENE
+coenzyme	I-GENE
+A	I-GENE
+reductase	I-GENE
+gene	I-GENE
+.	O
+
+E3	B-GENE
+/	I-GENE
+19K	I-GENE
+resides	O
+in	O
+the	O
+endoplasmic	O
+reticulum	O
+where	O
+it	O
+binds	O
+to	O
+MHC	B-GENE
+class	I-GENE
+I	I-GENE
+molecules	I-GENE
+,	O
+thereby	O
+preventing	O
+their	O
+transport	O
+to	O
+the	O
+cell	O
+surface	O
+.	O
+
+When	O
+the	O
+PHT	O
+and	O
+CSA	O
+groups	O
+were	O
+compared	O
+,	O
+Hyp	O
+levels	O
+were	O
+significantly	O
+higher	O
+in	O
+the	O
+PHT	O
+-	O
+GO	O
++	O
+group	O
+than	O
+in	O
+the	O
+CSA	O
+-	O
+GO	O
++	O
+group	O
+.	O
+
+Among	O
+the	O
+LE6	B-GENE
+deletions	O
+,	O
+only	O
+one	O
+had	O
+a	O
+reduced	O
+transformation	O
+efficiency	O
+,	O
+while	O
+seven	O
+transformed	O
+cells	O
+at	O
+least	O
+as	O
+efficiently	O
+as	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+LE6	I-GENE
+.	O
+
+ORF	B-GENE
+E8	I-GENE
+colinear	O
+with	O
+ORF	B-GENE
+E6	I-GENE
+,	O
+which	O
+could	O
+generate	O
+a	O
+50	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+with	O
+a	O
+hydrophobic	O
+segment	O
+,	O
+did	O
+not	O
+transform	O
+cells	O
+when	O
+cloned	O
+into	O
+the	O
+pZipNeo	O
+vector	O
+.	O
+
+Clb2	B-GENE
+/	O
+Cdc28	B-GENE
+kinase	O
+is	O
+not	O
+required	O
+for	O
+the	O
+repression	O
+of	O
+MCB	B-GENE
+-	I-GENE
+binding	I-GENE
+factor	I-GENE
+transcriptional	O
+activity	O
+in	O
+G2	O
+and	O
+M	O
+phase	O
+.	O
+
+The	O
+carboxy	O
+terminus	O
+of	O
+Mbp1	B-GENE
+is	O
+sufficient	O
+for	O
+interaction	O
+with	O
+Swi6	B-GENE
+,	O
+and	O
+the	O
+carboxy	O
+terminus	O
+of	O
+Swi6	B-GENE
+is	O
+required	O
+for	O
+interaction	O
+with	O
+Mbp1	B-GENE
+.	O
+
+Multiple	O
+single	O
+-	O
+stranded	O
+cis	O
+elements	O
+are	O
+associated	O
+with	O
+activated	O
+chromatin	O
+of	O
+the	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+in	O
+vivo	O
+.	O
+
+A	O
+new	O
+UASH	O
+consensus	O
+sequence	O
+derived	O
+from	O
+this	O
+mutational	O
+analysis	O
+closely	O
+matches	O
+a	O
+consensus	O
+Abf1	B-GENE
+binding	I-GENE
+site	I-GENE
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+analyzed	O
+human	B-GENE
+CTCF	I-GENE
+cDNA	I-GENE
+clones	O
+and	O
+show	O
+here	O
+that	O
+the	O
+ubiquitously	O
+expressed	O
+11	B-GENE
+-	I-GENE
+zinc	I-GENE
+-	I-GENE
+finger	I-GENE
+factor	I-GENE
+CTCF	I-GENE
+is	O
+an	O
+exceptionally	O
+highly	O
+conserved	O
+protein	O
+displaying	O
+93	O
+%	O
+identity	O
+between	O
+avian	O
+and	O
+human	O
+amino	O
+acid	O
+sequences	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+the	O
+P2	B-GENE
+-	I-GENE
+proximal	I-GENE
+CTCF	I-GENE
+binding	I-GENE
+site	I-GENE
+and	O
+transient	O
+-	O
+cotransfection	O
+experiments	O
+demonstrate	O
+that	O
+CTCF	B-GENE
+is	O
+a	O
+transcriptional	O
+repressor	O
+of	O
+the	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+myc	I-GENE
+gene	I-GENE
+.	O
+
+A	O
+chromosome	B-GENE
+transmission	I-GENE
+fidelity	I-GENE
+(	O
+ctf	B-GENE
+)	O
+mutant	O
+,	O
+s138	O
+,	O
+of	O
+Saccharomyces	O
+cerevisiae	O
+was	O
+identified	O
+by	O
+its	O
+centromere	O
+(	O
+CEN	O
+)	O
+transcriptional	O
+readthrough	O
+phenotype	O
+,	O
+suggesting	O
+perturbed	O
+kinetochore	O
+integrity	O
+in	O
+vivo	O
+.	O
+
+The	O
+growth	O
+defect	O
+of	O
+a	O
+reg1	B-GENE
+reg2	B-GENE
+double	I-GENE
+mutant	I-GENE
+is	O
+alleviated	O
+by	O
+a	O
+loss	O
+-	O
+of	O
+-	O
+function	O
+mutation	O
+in	O
+the	O
+SNF1	B-GENE
+-	I-GENE
+encoded	I-GENE
+protein	I-GENE
+kinase	I-GENE
+.	O
+
+Expression	O
+of	O
+the	O
+phenylalanine	B-GENE
+hydroxylase	I-GENE
+gene	I-GENE
+in	O
+livers	O
+and	O
+kidneys	O
+of	O
+rodents	O
+is	O
+activated	O
+at	O
+birth	O
+and	O
+is	O
+induced	O
+by	O
+glucocorticoids	O
+and	O
+cyclic	O
+AMP	O
+in	O
+the	O
+liver	O
+.	O
+
+We	O
+report	O
+here	O
+the	O
+identification	O
+of	O
+a	O
+cDNA	O
+that	O
+encodes	O
+a	O
+new	O
+member	O
+of	O
+the	O
+GTPase	B-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+(	O
+GAP	B-GENE
+)	O
+family	O
+of	O
+GTPase	B-GENE
+regulators	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+further	O
+investigated	O
+the	O
+regulation	O
+of	O
+the	O
+synthesis	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+mos	I-GENE
+oncogene	I-GENE
+product	I-GENE
+,	O
+which	O
+is	O
+necessary	O
+for	O
+the	O
+activation	O
+of	O
+Cdc2	B-GENE
+.	O
+
+The	O
+heterogeneity	O
+of	O
+bovine	B-GENE
+IgG2	I-GENE
+-	I-GENE
+-	I-GENE
+VIII	I-GENE
+.	O
+
+The	O
+ability	O
+of	O
+BCL	B-GENE
+-	I-GENE
+6	I-GENE
+to	O
+function	O
+as	O
+a	O
+transcriptional	O
+repressor	O
+may	O
+contribute	O
+to	O
+its	O
+ability	O
+to	O
+transform	O
+B	O
+lymphocytes	O
+in	O
+diffuse	O
+large	O
+cell	O
+lymphoma	O
+.	O
+
+Positioning	O
+this	O
+uORF	O
+,	O
+together	O
+with	O
+its	O
+accompanying	O
+Kozak	O
+sequences	O
+,	O
+between	O
+a	O
+heterologous	O
+promoter	O
+from	O
+SV40	O
+and	O
+a	O
+CAT	B-GENE
+reporter	I-GENE
+gene	I-GENE
+resulted	O
+in	O
+marked	O
+inhibition	O
+of	O
+CAT	B-GENE
+protein	I-GENE
+production	O
+without	O
+a	O
+decrease	O
+in	O
+CAT	B-GENE
+mRNA	I-GENE
+.	O
+
+A	O
+secondary	O
+spread	O
+of	O
+an	O
+imported	O
+methicillin	O
+-	O
+resistant	O
+Staphylococcus	O
+aureus	O
+strain	O
+(	O
+MRSA	O
+)	O
+to	O
+two	O
+other	O
+patients	O
+occurred	O
+within	O
+a	O
+Danish	O
+surgical	O
+ward	O
+in	O
+spite	O
+of	O
+isolation	O
+of	O
+a	O
+multitraumatized	O
+index	O
+-	O
+patient	O
+immediately	O
+after	O
+arrival	O
+from	O
+a	O
+hospital	O
+in	O
+the	O
+Mediterranean	O
+area	O
+.	O
+
+Mesial	O
+temporal	O
+sclerosis	O
+was	O
+characterized	O
+by	O
+severe	O
+neuronal	O
+loss	O
+accompanied	O
+by	O
+gliosis	O
+occurring	O
+in	O
+the	O
+CA1	O
+/	O
+prosubiculum	O
+(	O
+27	O
+patients	O
+,	O
+100	O
+%	O
+)	O
+,	O
+focally	O
+in	O
+the	O
+dentate	O
+gyrus	O
+(	O
+12	O
+patients	O
+,	O
+44	O
+%	O
+)	O
+,	O
+and	O
+in	O
+the	O
+CA4	O
+region	O
+(	O
+11	O
+patients	O
+,	O
+41	O
+%	O
+)	O
+.	O
+
+Mesial	O
+temporal	O
+sclerosis	O
+.	O
+
+More	O
+specific	O
+adverse	O
+events	O
+,	O
+also	O
+frequently	O
+considered	O
+as	O
+dose	O
+-	O
+limiting	O
+toxicities	O
+,	O
+include	O
+hypotension	O
+with	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+severe	O
+headache	O
+or	O
+skin	O
+rash	O
+with	O
+IL	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+and	O
+nasal	O
+congestion	O
+and	O
+gastroduodenal	O
+lesions	O
+with	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+.	O
+
+Therefore	O
+,	O
+magnetic	O
+resonance	O
+imaging	O
+was	O
+used	O
+to	O
+determine	O
+liver	O
+volume	O
+in	O
+pediatric	O
+and	O
+adolescent	O
+patients	O
+,	O
+in	O
+whom	O
+systemic	O
+clearance	O
+of	O
+three	O
+model	O
+substrates	O
+[	O
+lorazepam	O
+(	O
+0	O
+.	O
+03	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+antipyrine	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+and	O
+indocyanine	O
+green	O
+(	O
+ICG	O
+;	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+]	O
+was	O
+also	O
+determined	O
+.	O
+
+A	O
+mutational	O
+analysis	O
+has	O
+resolved	O
+a	O
+region	O
+of	O
+seven	O
+amino	O
+acids	O
+(	O
+amino	O
+acids	O
+26	O
+-	O
+32	O
+)	O
+in	O
+the	O
+N	O
+-	O
+terminus	O
+of	O
+Bob1	B-GENE
+that	O
+are	O
+important	O
+for	O
+contacting	O
+the	O
+DNA	B-GENE
+binding	I-GENE
+POU	I-GENE
+domain	I-GENE
+of	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+or	O
+Oct	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+155	O
+aa	O
+,	O
+shares	O
+78	O
+%	O
+identity	O
+with	O
+the	O
+analogous	O
+region	O
+of	O
+Xenopus	O
+laevis	O
+FGF3	B-GENE
+and	O
+72	O
+%	O
+identity	O
+with	O
+the	O
+product	O
+of	O
+the	O
+more	O
+distantly	O
+related	O
+human	O
+gene	O
+.	O
+
+The	O
+transcription	O
+start	O
+point	O
+of	O
+the	O
+proximal	O
+promoter	O
+aligns	O
+to	O
+that	O
+of	O
+mouse	O
+promoter	O
+P3	O
+and	O
+lies	O
+within	O
+a	O
+conserved	O
+region	O
+of	O
+sequence	O
+.	O
+
+A	O
+novel	O
+gene	O
+designated	O
+cmr	B-GENE
+,	O
+which	O
+mapped	O
+to	O
+18	O
+.	O
+8	O
+min	O
+of	O
+the	O
+Escherichia	O
+coli	O
+K	O
+-	O
+12	O
+genome	O
+,	O
+was	O
+shown	O
+to	O
+mediate	O
+resistance	O
+to	O
+chloramphenicol	O
+when	O
+it	O
+was	O
+expressed	O
+from	O
+a	O
+multicopy	O
+vector	O
+.	O
+
+In	O
+addition	O
+,	O
+5	O
+'	O
+deletions	O
+removing	O
+all	O
+but	O
+34	O
+bp	O
+upstream	O
+of	O
+the	O
+transcription	O
+start	O
+point	O
+retained	O
+greater	O
+than	O
+90	O
+%	O
+promoter	O
+activity	O
+,	O
+suggesting	O
+that	O
+the	O
+-	O
+35	O
+hexamer	O
+was	O
+not	O
+essential	O
+for	O
+promoter	O
+activity	O
+.	O
+
+The	O
+DNA	O
+sequence	O
+immediately	O
+upstream	O
+from	O
+the	O
+-	O
+10	O
+hexamer	O
+contained	O
+the	O
+TGn	O
+motif	O
+described	O
+as	O
+an	O
+extended	O
+-	O
+10	O
+region	O
+in	O
+prokaryotic	O
+promoters	O
+.	O
+
+An	O
+apparent	O
+ufo	B-GENE
+mRNA	I-GENE
+overexpression	O
+was	O
+not	O
+found	O
+in	O
+any	O
+of	O
+the	O
+positive	O
+leukemia	O
+cell	O
+lines	O
+,	O
+but	O
+was	O
+identified	O
+in	O
+the	O
+drug	O
+-	O
+resistant	O
+subclones	O
+of	O
+the	O
+cervix	O
+carcinoma	O
+cell	O
+line	O
+HeLa	O
+.	O
+
+We	O
+conclude	O
+from	O
+these	O
+studies	O
+that	O
+CKII	B-GENE
+may	O
+act	O
+as	O
+a	O
+positive	O
+regulator	O
+of	O
+myogenesis	O
+by	O
+preventing	O
+E	B-GENE
+protein	I-GENE
+homodimers	I-GENE
+from	O
+binding	O
+to	O
+muscle	O
+gene	O
+regulatory	O
+elements	O
+.	O
+
+The	O
+role	O
+of	O
+negative	O
+regulators	O
+such	O
+as	O
+NCE3	B-GENE
+,	O
+as	O
+well	O
+as	O
+the	O
+previously	O
+described	O
+SIN5	B-GENE
+gene	I-GENE
+,	O
+in	O
+determining	O
+the	O
+promoter	O
+specificity	O
+of	O
+homologous	O
+activators	O
+is	O
+discussed	O
+.	O
+
+Transcriptional	O
+regulators	O
+utilizing	O
+the	O
+POU	B-GENE
+domain	I-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+motif	I-GENE
+have	O
+been	O
+shown	O
+to	O
+form	O
+multi	O
+-	O
+protein	O
+complexes	O
+dependent	O
+on	O
+the	O
+POU	B-GENE
+domain	I-GENE
+itself	O
+and	O
+its	O
+flexible	O
+recognition	O
+of	O
+various	O
+octamer	O
+sequence	O
+elements	O
+.	O
+
+We	O
+found	O
+strand	O
+selective	O
+repair	O
+in	O
+DNA	O
+fragments	O
+within	O
+two	O
+active	O
+genes	O
+,	O
+DHFR	B-GENE
+and	O
+an	O
+unknown	O
+gene	O
+adjacent	O
+to	O
+DHFR	B-GENE
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+:	O
+Coronal	O
+3D	O
+GRE	O
+imaging	O
+was	O
+used	O
+to	O
+study	O
+the	O
+volar	O
+,	O
+middle	O
+,	O
+and	O
+dorsal	O
+portions	O
+of	O
+the	O
+SLL	O
+in	O
+14	O
+patients	O
+with	O
+an	O
+arthroscopically	O
+normal	O
+SLL	O
+and	O
+in	O
+five	O
+cadaveric	O
+wrists	O
+that	O
+had	O
+a	O
+normal	O
+SLL	O
+proved	O
+with	O
+dissection	O
+.	O
+
+In	O
+an	O
+effort	O
+to	O
+contribute	O
+to	O
+the	O
+transcript	O
+map	O
+of	O
+human	O
+chromosome	O
+21	O
+and	O
+the	O
+understanding	O
+of	O
+the	O
+pathophysiology	O
+of	O
+trisomy	O
+21	O
+,	O
+we	O
+have	O
+used	O
+exon	O
+trapping	O
+to	O
+identify	O
+fragments	O
+of	O
+chromosome	O
+21	O
+genes	O
+.	O
+
+Reproducing	O
+populations	O
+of	O
+this	O
+aphid	O
+were	O
+first	O
+detected	O
+in	O
+Puerto	O
+Rico	O
+in	O
+April	O
+1992	O
+.	O
+
+The	O
+model	O
+captures	O
+the	O
+essence	O
+of	O
+predator	O
+-	O
+prey	O
+dynamics	O
+to	O
+provide	O
+reasonable	O
+predictions	O
+of	O
+population	O
+patterns	O
+.	O
+
+At	O
+cuticular	O
+positions	O
+exhibiting	O
+the	O
+Brd	B-GENE
+bristle	I-GENE
+loss	I-GENE
+phenotype	I-GENE
+,	O
+we	O
+have	O
+found	O
+that	O
+the	O
+progeny	O
+of	O
+the	O
+multiplied	O
+SOPs	O
+develop	O
+aberrantly	O
+,	O
+in	O
+that	O
+neurons	O
+and	O
+thecogen	O
+(	O
+sheath	O
+)	O
+cells	O
+appear	O
+but	O
+not	O
+trichogen	O
+(	O
+shaft	O
+)	O
+and	O
+tormogen	O
+(	O
+socket	O
+)	O
+cells	O
+.	O
+
+Transcriptional	O
+blockade	O
+was	O
+reversed	O
+by	O
+co	O
+-	O
+transfections	O
+of	O
+a	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+SRF	I-GENE
+expression	O
+vector	O
+,	O
+but	O
+was	O
+not	O
+rescued	O
+by	O
+the	O
+expression	O
+of	O
+other	O
+myogenic	O
+factors	O
+,	O
+such	O
+as	O
+MyoD	B-GENE
+and	O
+Mef	B-GENE
+-	I-GENE
+2C	I-GENE
+.	O
+
+The	O
+mMIWC1	B-GENE
+promoter	I-GENE
+was	O
+identified	O
+and	O
+contained	O
+TATA	O
+,	O
+CAAT	O
+,	O
+GATA	O
+,	O
+and	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+elements	I-GENE
+;	O
+primer	O
+extension	O
+revealed	O
+mMIWC	B-GENE
+transcription	O
+initiation	O
+at	O
+621	O
+bp	O
+upstream	O
+from	O
+the	O
+mMIWC1	B-GENE
+translational	O
+initiation	O
+site	O
+.	O
+
+Human	B-GENE
+MN	I-GENE
+/	I-GENE
+CA9	I-GENE
+gene	I-GENE
+,	O
+a	O
+novel	O
+member	O
+of	O
+the	O
+carbonic	B-GENE
+anhydrase	I-GENE
+family	I-GENE
+:	O
+structure	O
+and	O
+exon	O
+to	O
+protein	O
+domain	O
+relationships	O
+.	O
+
+The	O
+exon	O
+-	O
+intron	O
+distribution	O
+of	O
+Cdebp	B-GENE
+appears	O
+strikingly	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+App	B-GENE
+gene	I-GENE
+in	O
+the	O
+regions	O
+encoding	O
+the	O
+conserved	O
+domains	O
+,	O
+with	O
+a	O
+divergent	O
+structure	O
+in	O
+the	O
+other	O
+parts	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+reveals	O
+that	O
+the	O
+gene	O
+encodes	O
+a	O
+protein	O
+highly	O
+homologous	O
+to	O
+rat	B-GENE
+CRP1	I-GENE
+.	O
+
+The	O
+gene	O
+was	O
+expressed	O
+as	O
+an	O
+approximately	O
+1	O
+.	O
+5	O
+-	O
+kb	O
+mRNA	O
+in	O
+most	O
+nonlymphoid	O
+human	O
+cells	O
+/	O
+tissues	O
+including	O
+prostate	O
+,	O
+lung	O
+,	O
+liver	O
+,	O
+and	O
+colon	O
+.	O
+
+Both	O
+of	O
+these	O
+domains	O
+have	O
+striking	O
+sequence	O
+homology	O
+with	O
+human	O
+SIM	B-GENE
+and	O
+Drosophila	O
+SIM	B-GENE
+proteins	O
+.	O
+
+We	O
+have	O
+obtained	O
+the	O
+human	B-GENE
+EP4	I-GENE
+receptor	I-GENE
+gene	I-GENE
+sequence	I-GENE
+and	O
+determined	O
+its	O
+structure	O
+relative	O
+to	O
+EP4R	B-GENE
+cDNA	I-GENE
+synthesized	O
+from	O
+peripheral	O
+blood	O
+lymphocytes	O
+.	O
+
+Some	O
+users	O
+will	O
+willingly	O
+comply	O
+with	O
+management	O
+measures	O
+,	O
+other	O
+users	O
+will	O
+comply	O
+in	O
+response	O
+to	O
+education	O
+,	O
+but	O
+there	O
+will	O
+be	O
+another	O
+group	O
+who	O
+will	O
+only	O
+respond	O
+to	O
+enforcement	O
+activities	O
+.	O
+
+Three	O
+separate	O
+activation	O
+subdomains	O
+,	O
+and	O
+one	O
+negative	O
+-	O
+acting	O
+region	O
+,	O
+which	O
+function	O
+in	O
+yeast	O
+were	O
+located	O
+in	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+region	O
+of	O
+NIT4	B-GENE
+.	O
+
+The	O
+front	O
+(	O
+F	O
+)	O
+interaction	O
+occurs	O
+ahead	O
+of	O
+the	O
+growing	O
+end	O
+of	O
+RNA	O
+.	O
+
+Collectively	O
+,	O
+these	O
+data	O
+indicate	O
+that	O
+HIP	B-GENE
+is	O
+a	O
+membrane	O
+-	O
+associated	O
+HP	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+expressed	O
+on	O
+the	O
+surface	O
+of	O
+normal	O
+human	O
+uterine	O
+epithelia	O
+and	O
+uterine	O
+epithelial	O
+cell	O
+lines	O
+.	O
+
+The	O
+corresponding	O
+gene	O
+was	O
+identified	O
+in	O
+the	O
+GenBankTM	O
+data	O
+base	O
+by	O
+sequence	O
+alignment	O
+and	O
+termed	O
+RPS30A	B-GENE
+.	O
+
+The	O
+location	O
+of	O
+multiple	O
+GRK2	B-GENE
+and	O
+GRK5	B-GENE
+phosphoacceptor	I-GENE
+sites	I-GENE
+at	O
+the	O
+extreme	O
+carboxyl	O
+terminus	O
+of	O
+the	O
+beta2AR	B-GENE
+is	O
+highly	O
+reminiscent	O
+of	O
+GRK1	B-GENE
+-	O
+mediated	O
+phosphorylation	O
+of	O
+rhodopsin	B-GENE
+.	O
+
+This	O
+regulation	O
+could	O
+not	O
+be	O
+appreciably	O
+modified	O
+by	O
+enhanced	O
+expression	O
+of	O
+STAT	B-GENE
+proteins	I-GENE
+.	O
+
+Receptors	O
+for	O
+interleukin	B-GENE
+(	I-GENE
+IL	I-GENE
+)	I-GENE
+-	I-GENE
+10	I-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+type	I-GENE
+cytokines	I-GENE
+use	O
+similar	O
+signaling	O
+mechanisms	O
+for	O
+inducing	O
+transcription	O
+through	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+response	O
+elements	O
+.	O
+
+Specifically	O
+,	O
+the	O
+deduced	O
+FR	B-GENE
+-	I-GENE
+19	I-GENE
+amino	I-GENE
+acid	I-GENE
+sequence	I-GENE
+has	O
+approximately89	O
+,	O
+77	O
+,	O
+and	O
+68	O
+%	O
+overall	O
+identity	O
+to	O
+chicken	B-GENE
+TEF	I-GENE
+-	I-GENE
+1A	I-GENE
+,	O
+mouse	B-GENE
+TEF	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+mouse	B-GENE
+embryonic	I-GENE
+TEA	I-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+factor	I-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+receptor	B-GENE
+for	I-GENE
+hyaluronan	I-GENE
+mediated	I-GENE
+motility	I-GENE
+(	B-GENE
+RHAMM	I-GENE
+)	I-GENE
+gene	I-GENE
+expression	O
+is	O
+markedly	O
+elevated	O
+in	O
+fibrosarcomas	O
+exposed	O
+to	O
+transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta1	I-GENE
+(	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+)	O
+.	O
+
+Oncogenic	B-GENE
+Raf	I-GENE
+-	I-GENE
+1	I-GENE
+activates	O
+p70	B-GENE
+S6	I-GENE
+kinase	I-GENE
+via	O
+a	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+-	O
+independent	O
+pathway	O
+.	O
+
+Hydropathy	O
+analysis	O
+of	O
+KCC1	B-GENE
+indicates	O
+structural	O
+homology	O
+to	O
+NKCC	B-GENE
+,	O
+including	O
+12	O
+transmembrane	O
+domains	O
+,	O
+a	O
+large	O
+extracellular	O
+loop	O
+with	O
+potential	O
+N	O
+-	O
+linked	O
+glycosylation	O
+sites	O
+,	O
+and	O
+cytoplasmic	O
+N	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+regions	O
+.	O
+
+This	O
+protein	O
+with	O
+a	O
+hydrophobic	O
+amino	O
+terminus	O
+appears	O
+to	O
+be	O
+a	O
+secreted	O
+protein	O
+.	O
+
+Notably	O
+,	O
+SRF	B-GENE
+has	O
+been	O
+found	O
+to	O
+be	O
+a	O
+key	O
+regulator	O
+of	O
+members	O
+of	O
+a	O
+class	O
+of	O
+cellular	O
+response	O
+genes	O
+termed	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+genes	I-GENE
+(	O
+IEGs	B-GENE
+)	O
+,	O
+many	O
+of	O
+which	O
+are	O
+believed	O
+to	O
+be	O
+involved	O
+in	O
+regulating	O
+cell	O
+growth	O
+and	O
+differentiation	O
+.	O
+
+The	O
+final	O
+sigma54	B-GENE
+-	I-GENE
+dependent	I-GENE
+DmpR	I-GENE
+activator	I-GENE
+regulates	O
+transcription	O
+of	O
+the	O
+dmp	B-GENE
+operon	I-GENE
+that	O
+encodes	O
+the	O
+enzymes	O
+for	O
+catabolism	O
+of	O
+(	O
+methyl	O
+)	O
+phenols	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+have	O
+cloned	O
+the	O
+human	B-GENE
+DSG3	I-GENE
+gene	I-GENE
+and	O
+examined	O
+the	O
+transcriptional	O
+regulation	O
+of	O
+its	O
+expression	O
+.	O
+
+Clinical	O
+evaluation	O
+of	O
+the	O
+Allergan	O
+Humphrey	O
+500	O
+autorefractor	O
+and	O
+the	O
+Nidek	O
+AR	O
+-	O
+1000	O
+autorefractor	O
+.	O
+
+None	O
+of	O
+the	O
+five	O
+proprotein	O
+processing	O
+proteases	O
+tested	O
+were	O
+capable	O
+of	O
+cleaving	O
+human	B-GENE
+pro	I-GENE
+-	I-GENE
+LPH	I-GENE
+,	O
+strongly	O
+suggesting	O
+that	O
+they	O
+are	O
+not	O
+involved	O
+in	O
+the	O
+maturation	O
+of	O
+this	O
+enzyme	O
+.	O
+
+These	O
+changes	O
+may	O
+be	O
+the	O
+result	O
+of	O
+,	O
+on	O
+the	O
+one	O
+hand	O
+,	O
+an	O
+increased	O
+sensitivity	O
+of	O
+the	O
+neuromuscular	O
+transmission	O
+and	O
+/	O
+or	O
+decreased	O
+muscle	O
+contractility	O
+and	O
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+the	O
+result	O
+of	O
+a	O
+reduced	O
+plasma	O
+clearance	O
+during	O
+hypothermia	O
+.	O
+
+By	O
+using	O
+interleukin	B-GENE
+-	I-GENE
+3	I-GENE
+-	O
+dependent	O
+cells	O
+that	O
+ectopically	O
+express	O
+the	O
+three	O
+ErbB	B-GENE
+proteins	I-GENE
+or	O
+their	O
+combinations	O
+,	O
+we	O
+found	O
+that	O
+ErbB	B-GENE
+-	I-GENE
+3	I-GENE
+is	O
+devoid	O
+of	O
+any	O
+biological	O
+activity	O
+but	O
+both	O
+ErbB	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+ErbB	B-GENE
+-	I-GENE
+2	I-GENE
+can	O
+reconstitute	O
+its	O
+extremely	O
+potent	O
+mitogenic	O
+activity	O
+.	O
+
+ZIOS	O
+was	O
+significantly	O
+more	O
+sensitive	O
+than	O
+all	O
+subsequent	O
+methods	O
+,	O
+and	O
+Ptc	O
+,	O
+O2	O
+was	O
+significantly	O
+more	O
+sensitive	O
+than	O
+FEV1	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+direct	O
+cDNA	O
+mapping	O
+using	O
+fluorescence	O
+in	O
+situ	O
+hybridization	O
+provides	O
+an	O
+accurate	O
+and	O
+rapid	O
+approach	O
+to	O
+the	O
+definition	O
+of	O
+a	O
+transcribed	O
+map	O
+of	O
+the	O
+human	O
+genome	O
+.	O
+
+YAC	O
+and	O
+cosmid	O
+contigs	O
+spanning	O
+the	O
+Batten	B-GENE
+disease	I-GENE
+(	O
+CLN3	B-GENE
+)	O
+region	O
+at	O
+16p12	O
+.	O
+1	O
+-	O
+p11	O
+.	O
+2	O
+.	O
+
+Isolation	O
+of	O
+a	O
+near	O
+full	O
+-	O
+length	O
+cDNA	O
+from	O
+a	O
+human	O
+fetal	O
+brain	O
+cDNA	O
+library	O
+revealed	O
+a	O
+protein	B-GENE
+serine	I-GENE
+-	I-GENE
+threonine	I-GENE
+phosphatase	I-GENE
+with	O
+a	O
+tetratricopeptide	O
+motif	O
+,	O
+almost	O
+identical	O
+to	O
+human	B-GENE
+PPP5C	I-GENE
+(	O
+PP5	B-GENE
+)	O
+and	O
+highly	O
+homologous	O
+to	O
+rat	B-GENE
+PPT	I-GENE
+.	O
+
+Ly	B-GENE
+-	I-GENE
+49	I-GENE
+is	O
+a	O
+family	B-GENE
+type	I-GENE
+II	I-GENE
+transmembrane	I-GENE
+proteins	I-GENE
+encoded	O
+by	O
+a	O
+gene	O
+cluster	O
+on	O
+murine	O
+chromosome	O
+6	O
+.	O
+
+The	O
+Dox	B-GENE
+-	I-GENE
+A2	I-GENE
+ORF	I-GENE
+driven	O
+by	O
+the	O
+TDH3	B-GENE
+promoter	I-GENE
+complemented	O
+the	O
+phenotype	O
+of	O
+a	O
+strain	O
+deleted	O
+for	O
+sun2	B-GENE
+.	O
+
+The	O
+introduction	O
+of	O
+hARF4	B-GENE
+to	O
+the	O
+cells	O
+maintained	O
+the	O
+balance	O
+between	O
+cytosolic	O
+and	O
+membrane	O
+-	O
+associated	O
+Sec7p	B-GENE
+pools	O
+.	O
+
+Vacuolar	O
+membrane	O
+vesicles	O
+from	O
+hum1	B-GENE
+mutants	I-GENE
+lack	O
+all	O
+Ca2	O
++	O
+/	O
+H	O
++	O
+antiport	O
+activity	O
+,	O
+demonstrating	O
+that	O
+Hum1p	B-GENE
+catalyzes	O
+the	O
+exchange	O
+of	O
+Ca2	O
++	O
+for	O
+H	O
++	O
+across	O
+the	O
+yeast	O
+vacuolar	O
+membrane	O
+.	O
+
+Detailed	O
+mutagenesis	O
+of	O
+the	O
+element	O
+'	O
+s	O
+rare	O
+-	O
+codon	O
+/	O
+AU	O
+-	O
+rich	O
+sequence	O
+boundary	O
+revealed	O
+that	O
+the	O
+destabilizing	O
+activity	O
+of	O
+the	O
+MATalpha1	B-GENE
+IE	I-GENE
+is	O
+observed	O
+when	O
+the	O
+terminal	O
+codon	O
+of	O
+the	O
+element	O
+'	O
+s	O
+rare	O
+-	O
+codon	O
+interval	O
+is	O
+translated	O
+.	O
+
+FTF	B-GENE
+is	O
+also	O
+abundantly	O
+expressed	O
+in	O
+the	O
+pancreas	O
+and	O
+may	O
+exert	O
+differentiation	O
+functions	O
+in	O
+endodermal	O
+sublineages	O
+,	O
+similar	O
+to	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+steroidogenic	O
+tissues	O
+.	O
+
+The	O
+incidence	O
+of	O
+cardiac	O
+death	O
+(	O
+one	O
+per	O
+group	O
+)	O
+,	O
+Q	O
+wave	O
+MI	O
+(	O
+propofol	O
+,	O
+n	O
+=	O
+7	O
+;	O
+midazolam	O
+,	O
+n	O
+=	O
+3	O
+;	O
+P	O
+=	O
+0	O
+.	O
+27	O
+)	O
+,	O
+or	O
+non	O
+Q	O
+wave	O
+MI	O
+(	O
+propofol	O
+,	O
+n	O
+=	O
+16	O
+;	O
+midazolam	O
+,	O
+n	O
+=	O
+18	O
+;	O
+P	O
+=	O
+0	O
+.	O
+81	O
+)	O
+did	O
+not	O
+differ	O
+between	O
+treatment	O
+groups	O
+.	O
+
+Cluster	O
+formation	O
+of	O
+E	B-GENE
+-	I-GENE
+cadherin	I-GENE
+on	O
+the	O
+cell	O
+surface	O
+is	O
+believed	O
+to	O
+be	O
+of	O
+major	O
+importance	O
+for	O
+cell	O
+-	O
+cell	O
+adhesion	O
+.	O
+
+DNA	B-GENE
+polymerase	I-GENE
+E	I-GENE
+,	O
+DNA	B-GENE
+ligase	I-GENE
+III	I-GENE
+and	O
+a	O
+DNA	O
+structure	O
+-	O
+specific	O
+endonuclease	O
+co	O
+-	O
+purify	O
+with	O
+the	O
+five	O
+polypeptide	O
+complex	O
+.	O
+
+By	O
+using	O
+reporter	O
+gene	O
+constructs	O
+,	O
+it	O
+is	O
+shown	O
+that	O
+upstream	O
+sequences	O
+of	O
+the	O
+P1	O
+promoter	O
+contain	O
+several	O
+regions	O
+that	O
+modulate	O
+the	O
+expression	O
+either	O
+positively	O
+or	O
+negatively	O
+.	O
+
+The	O
+factor	O
+structure	O
+of	O
+"	O
+schizotypal	O
+'	O
+traits	O
+:	O
+a	O
+large	O
+replication	O
+study	O
+.	O
+
+Interestingly	O
+,	O
+however	O
+,	O
+it	O
+is	O
+homologous	O
+to	O
+several	O
+expressed	O
+sequence	O
+tags	O
+(	O
+EST	O
+)	O
+of	O
+unknown	O
+function	O
+from	O
+Caenorhabditis	O
+elegans	O
+,	O
+Oryza	O
+sativa	O
+and	O
+Homo	O
+sapiens	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+bilinear	O
+model	O
+provided	O
+a	O
+significantly	O
+better	O
+fit	O
+to	O
+the	O
+acuity	O
+outcome	O
+data	O
+.	O
+
+Outcome	O
+of	O
+severe	O
+congenital	O
+hypothyroidism	O
+.	O
+
+Nonreturn	O
+rates	O
+can	O
+be	O
+used	O
+to	O
+derive	O
+more	O
+elementary	O
+biological	O
+measures	O
+for	O
+reproductive	O
+efficiency	O
+,	O
+such	O
+as	O
+conception	O
+rate	O
+and	O
+calving	O
+rate	O
+,	O
+which	O
+separately	O
+might	O
+be	O
+more	O
+reliable	O
+than	O
+nonreturn	O
+rate	O
+itself	O
+to	O
+evaluate	O
+the	O
+fertility	O
+of	O
+a	O
+bull	O
+or	O
+the	O
+performance	O
+of	O
+an	O
+AI	O
+technician	O
+.	O
+
+However	O
+,	O
+if	O
+EMPD	O
+involves	O
+the	O
+glans	O
+penis	O
+or	O
+perianal	O
+area	O
+,	O
+a	O
+search	O
+for	O
+internal	O
+malignancy	O
+is	O
+still	O
+warranted	O
+.	O
+
+The	O
+mean	O
+values	O
+of	O
+protease	O
+activity	O
+were	O
+significantly	O
+higher	O
+in	O
+the	O
+test	O
+groups	O
+than	O
+in	O
+the	O
+control	O
+group	O
+at	O
+baseline	O
+.	O
+
+Each	O
+half	O
+molecule	O
+contains	O
+four	O
+disulfide	O
+linkages	O
+and	O
+four	O
+cis	O
+peptides	O
+.	O
+
+Only	O
+fully	O
+processed	O
+Pra	B-GENE
+(	O
+N0	O
+and	O
+Nb	O
+)	O
+and	O
+ICP35	B-GENE
+(	O
+ICP35	B-GENE
+e	I-GENE
+,	I-GENE
+f	I-GENE
+)	O
+are	O
+present	O
+in	O
+B	O
+capsids	O
+,	O
+which	O
+are	O
+believed	O
+to	O
+be	O
+precursors	O
+of	O
+mature	O
+virions	O
+.	O
+
+However	O
+,	O
+one	O
+3	O
+'	O
+splice	O
+site	O
+,	O
+located	O
+at	O
+nucleotide	O
+(	O
+nt	O
+)	O
+3225	O
+,	O
+is	O
+used	O
+for	O
+the	O
+processing	O
+of	O
+most	O
+BPV	O
+-	O
+1	O
+pre	O
+-	O
+mRNAs	O
+in	O
+BPV	O
+-	O
+1	O
+-	O
+transformed	O
+C127	O
+cells	O
+and	O
+at	O
+early	O
+to	O
+intermediate	O
+times	O
+in	O
+productively	O
+infected	O
+warts	O
+.	O
+
+Here	O
+,	O
+the	O
+cloning	O
+and	O
+characterization	O
+of	O
+S	B-GENE
+-	I-GENE
+RNase	I-GENE
+genes	I-GENE
+from	O
+two	O
+species	O
+of	O
+Rosaceae	O
+,	O
+apple	O
+(	O
+Malus	O
+x	O
+domestica	O
+)	O
+and	O
+Japanese	O
+pear	O
+(	O
+Pyrus	O
+serotina	O
+)	O
+is	O
+described	O
+and	O
+these	O
+sequences	O
+are	O
+compared	O
+with	O
+those	O
+of	O
+other	O
+T2	B-GENE
+-	I-GENE
+type	I-GENE
+RNases	I-GENE
+.	O
+
+A	O
+phylogenetic	O
+tree	O
+of	O
+members	O
+of	O
+the	O
+T2	B-GENE
+/	I-GENE
+S	I-GENE
+-	I-GENE
+RNase	I-GENE
+superfamily	I-GENE
+in	O
+plants	O
+was	O
+obtained	O
+.	O
+
+In	O
+a	O
+Hoosier	O
+Oncology	O
+Group	O
+randomized	O
+study	O
+involving	O
+extensive	O
+-	O
+disease	O
+SCLC	O
+patients	O
+,	O
+VIP	O
+was	O
+superior	O
+to	O
+etoposide	O
+/	O
+cisplatin	O
+with	O
+regard	O
+to	O
+median	O
+time	O
+to	O
+progression	O
+(	O
+6	O
+.	O
+6	O
+v	O
+5	O
+.	O
+8	O
+months	O
+)	O
+,	O
+median	O
+survival	O
+times	O
+(	O
+9	O
+.	O
+1	O
+v	O
+7	O
+.	O
+3	O
+months	O
+)	O
+,	O
+and	O
+2	O
+-	O
+and	O
+3	O
+-	O
+year	O
+survival	O
+rates	O
+(	O
+13	O
+%	O
+v	O
+5	O
+%	O
+and	O
+5	O
+%	O
+v	O
+0	O
+%	O
+,	O
+respectively	O
+)	O
+.	O
+
+It	O
+was	O
+shown	O
+that	O
+administration	O
+of	O
+immunomodulator	O
+neurotropin	B-GENE
+(	O
+NSP	B-GENE
+)	O
+results	O
+in	O
+more	O
+steady	O
+consolidation	O
+and	O
+retention	O
+of	O
+feeding	O
+and	O
+avoidance	O
+behavior	O
+,	O
+and	O
+some	O
+neurophysiological	O
+mechanisms	O
+of	O
+that	O
+phenomena	O
+were	O
+revealed	O
+.	O
+
+Sestamibi	O
+scintigraphy	O
+,	O
+performed	O
+in	O
+70	O
+patients	O
+,	O
+was	O
+less	O
+sensitive	O
+than	O
+ultrasonography	O
+(	O
+80	O
+%	O
+)	O
+.	O
+
+Atopic	O
+allergy	O
+and	O
+other	O
+hypersensitivities	O
+.	O
+
+After	O
+6	O
+h	O
+of	O
+reperfusion	O
+,	O
+PO2	O
+/	O
+FlO2	O
+ratio	O
+was	O
+significantly	O
+better	O
+after	O
+Combined	O
+Therapy	O
+(	O
+372	O
++	O
+/	O
+-	O
+52	O
+mm	O
+Hg	O
+)	O
+than	O
+in	O
+the	O
+Recipient	O
+Instilled	O
+(	O
+117	O
++	O
+/	O
+-	O
+47	O
+mm	O
+Hg	O
+)	O
+and	O
+Control	O
+groups	O
+(	O
+87	O
++	O
+/	O
+-	O
+26	O
+mm	O
+Hg	O
+)	O
+,	O
+with	O
+intermediate	O
+values	O
+in	O
+Donor	O
+Aerosol	O
+dogs	O
+(	O
+232	O
++	O
+/	O
+-	O
+64	O
+mm	O
+Hg	O
+)	O
+.	O
+
+The	O
+euglobulin	B-GENE
+clot	O
+lysis	O
+time	O
+was	O
+slightly	O
+longer	O
+in	O
+the	O
+smokers	O
+than	O
+in	O
+the	O
+non	O
+-	O
+smokers	O
+in	O
+all	O
+three	O
+experimental	O
+situations	O
+,	O
+but	O
+the	O
+differences	O
+were	O
+not	O
+significant	O
+.	O
+
+HS	O
+inducibility	O
+required	O
+the	O
+HSE	O
+which	O
+was	O
+bound	O
+by	O
+HS	B-GENE
+transcription	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+HSF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+present	O
+in	O
+extracts	O
+prepared	O
+from	O
+cells	O
+exposed	O
+to	O
+HS	O
+.	O
+
+Although	O
+the	O
+DSK2	B-GENE
+-	I-GENE
+1	I-GENE
+mutation	I-GENE
+alters	O
+a	O
+conserved	O
+residue	O
+in	O
+the	O
+Dsk2p	B-GENE
+ubiquitin	B-GENE
+-	I-GENE
+like	I-GENE
+domain	I-GENE
+,	O
+we	O
+detect	O
+no	O
+differences	O
+in	O
+Dsk2p	B-GENE
+or	O
+Cdc31p	B-GENE
+stability	O
+.	O
+
+Consistent	O
+with	O
+this	O
+interpretation	O
+,	O
+recombinant	B-GENE
+CREB	I-GENE
+and	O
+activating	B-GENE
+transcription	I-GENE
+factor	I-GENE
+proteins	I-GENE
+bound	O
+the	O
+junB	B-GENE
+CRE	O
+-	O
+like	O
+site	O
+,	O
+but	O
+did	O
+not	O
+interact	O
+with	O
+a	O
+mutant	O
+CRE	O
+-	O
+like	O
+site	O
+.	O
+
+Collectively	O
+,	O
+these	O
+results	O
+suggest	O
+that	O
+components	O
+of	O
+the	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+signaling	O
+pathway	O
+are	O
+recruited	O
+by	O
+mIg	B-GENE
+to	O
+induce	O
+junB	B-GENE
+transcription	O
+.	O
+
+Immunofluorescence	O
+microscopy	O
+revealed	O
+extensive	O
+deposition	O
+of	O
+such	O
+extracellular	O
+matrices	O
+as	O
+type	B-GENE
+IV	I-GENE
+collagen	I-GENE
+and	O
+laminin	B-GENE
+in	O
+the	O
+vascular	O
+wall	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+compare	O
+pregnancy	O
+complications	O
+in	O
+women	O
+having	O
+genetic	O
+amniocentesis	O
+at	O
+11	O
+-	O
+14	O
+weeks	O
+versus	O
+those	O
+undergoing	O
+amniocentesis	O
+at	O
+16	O
+-	O
+19	O
+weeks	O
+'	O
+gestation	O
+.	O
+
+Three	O
+ORFs	O
+(	O
+9765orfR002	O
+,	O
+9765orfR011	O
+and	O
+9765orfR013	O
+)	O
+were	O
+found	O
+to	O
+be	O
+homologous	O
+with	O
+Schizosaccharomyces	O
+pombe	O
+polyadenylate	B-GENE
+binding	I-GENE
+protein	I-GENE
+,	O
+Escherichia	O
+coli	O
+hypothetical	O
+38	O
+.	O
+1	O
+-	O
+kDa	O
+protein	O
+in	O
+the	O
+BCR	B-GENE
+5	O
+'	O
+region	O
+,	O
+and	O
+transcription	O
+regulatory	O
+protein	O
+Swi3	B-GENE
+,	O
+respectively	O
+.	O
+
+Two	O
+new	O
+flavone	O
+glucosides	O
+,	O
+nevadensin	O
+5	O
+-	O
+O	O
+-	O
+beta	O
+-	O
+D	O
+-	O
+glucoside	O
+and	O
+nevadensin	O
+5	O
+-	O
+O	O
+-	O
+beta	O
+-	O
+D	O
+-	O
+glucosyl	O
+(	O
+1	O
+-	O
+-	O
+>	O
+6	O
+)	O
+beta	O
+-	O
+D	O
+-	O
+glucoside	O
+,	O
+have	O
+been	O
+isolated	O
+from	O
+the	O
+aerial	O
+parts	O
+of	O
+Lysionotus	O
+pauciflorus	O
+.	O
+
+Recently	O
+,	O
+our	O
+laboratory	O
+developed	O
+a	O
+screen	O
+that	O
+identified	O
+five	O
+multicopy	O
+suppressors	O
+that	O
+can	O
+rescue	O
+lethal	O
+strains	O
+of	O
+clathrin	B-GENE
+heavy	O
+chain	O
+-	O
+deficient	O
+yeast	O
+(	O
+Chc	B-GENE
+-	O
+scd1	B-GENE
+-	I-GENE
+i	I-GENE
+)	O
+to	O
+viability	O
+.	O
+
+Reproductive	O
+period	O
+affects	O
+water	O
+intake	O
+in	O
+heat	O
+-	O
+stressed	O
+dehydrated	O
+goats	O
+.	O
+
+The	O
+logistic	O
+regression	O
+analysis	O
+of	O
+the	O
+manual	O
+method	O
+(	O
+percentage	O
+normal	O
+morphology	O
+)	O
+and	O
+IVOS	O
+indicated	O
+that	O
+both	O
+were	O
+predictors	O
+of	O
+fertilization	O
+.	O
+
+METHODS	O
+:	O
+Rats	O
+received	O
+continuous	O
+intragastric	O
+infusion	O
+of	O
+elemental	O
+diet	O
+or	O
+with	O
+supplementation	O
+of	O
+oatbase	O
+,	O
+Lactobacillus	O
+reuteri	O
+R2LC	O
+,	O
+and	O
+Lactobacillus	O
+plantarum	O
+DSM	O
+9843	O
+,	O
+with	O
+and	O
+without	O
+fermentation	O
+,	O
+from	O
+the	O
+beginning	O
+of	O
+the	O
+study	O
+.	O
+
+However	O
+,	O
+D8	B-GENE
+binding	O
+was	O
+observed	O
+by	O
+nuclease	O
+protection	O
+with	O
+lactotroph	B-GENE
+-	I-GENE
+as	I-GENE
+well	I-GENE
+as	I-GENE
+somatotroph	I-GENE
+-	I-GENE
+like	I-GENE
+cell	I-GENE
+nuclear	I-GENE
+protein	I-GENE
+.	O
+
+The	O
+ability	O
+of	O
+A20	B-GENE
+to	O
+block	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activation	O
+was	O
+mapped	O
+to	O
+its	O
+C	O
+-	O
+terminal	O
+zinc	O
+finger	O
+domain	O
+.	O
+
+By	O
+using	O
+a	O
+DNA	O
+sequence	O
+selected	O
+for	O
+its	O
+ability	O
+to	O
+bind	O
+recombinant	B-GENE
+BCL	I-GENE
+-	I-GENE
+6	I-GENE
+in	O
+vitro	O
+,	O
+we	O
+show	O
+here	O
+that	O
+BCL	B-GENE
+-	I-GENE
+6	I-GENE
+is	O
+present	O
+in	O
+DNA	O
+-	O
+binding	O
+complexes	O
+in	O
+nuclear	O
+extracts	O
+from	O
+various	O
+B	O
+-	O
+cell	O
+lines	O
+.	O
+
+The	O
+predictive	O
+value	O
+of	O
+a	O
+positive	O
+flag	O
+was	O
+77	O
+.	O
+7	O
+%	O
+.	O
+
+Because	O
+chromosome	O
+X	O
+is	O
+frequently	O
+involved	O
+in	O
+structural	O
+alterations	O
+in	O
+neoplastic	O
+Syrian	O
+hamster	O
+cells	O
+transformed	O
+by	O
+chemical	O
+carcinogens	O
+and	O
+oncogenic	O
+viruses	O
+,	O
+the	O
+localization	O
+of	O
+the	O
+cph	B-GENE
+locus	I-GENE
+on	O
+this	O
+chromosome	O
+supports	O
+the	O
+notion	O
+that	O
+the	O
+cph	B-GENE
+oncogene	I-GENE
+plays	O
+a	O
+role	O
+in	O
+the	O
+malignant	O
+conversion	O
+of	O
+chemically	O
+transformed	O
+hamster	O
+fibroblasts	O
+.	O
+
+Gap1	B-GENE
+(	I-GENE
+IP4BP	I-GENE
+)	I-GENE
+,	O
+one	O
+of	O
+a	O
+member	O
+of	O
+Ras	B-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+proteins	I-GENE
+,	O
+has	O
+been	O
+identified	O
+as	O
+a	O
+specific	O
+inositol	B-GENE
+1	I-GENE
+,	I-GENE
+3	I-GENE
+,	I-GENE
+4	I-GENE
+,	I-GENE
+5	I-GENE
+-	I-GENE
+tetrakisphosphate	I-GENE
+(	I-GENE
+IP4	I-GENE
+)	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+Cullen	O
+,	O
+P	O
+.	O
+
+We	O
+previously	O
+described	O
+the	O
+purification	O
+of	O
+an	O
+83	B-GENE
+-	I-GENE
+kDa	I-GENE
+phosphatidic	I-GENE
+acid	I-GENE
+phosphatase	I-GENE
+(	O
+PAP	B-GENE
+)	O
+from	O
+the	O
+porcine	O
+thymus	O
+membranes	O
+(	O
+Kanoh	O
+,	O
+H	O
+.	O
+,	O
+Imai	O
+,	O
+S	O
+.	O
+-	O
+i	O
+.	O
+,	O
+Yamada	O
+,	O
+K	O
+.	O
+and	O
+Sakane	O
+,	O
+F	O
+.	O
+(	O
+1992	O
+)	O
+J	O
+.	O
+
+A	O
+cDNA	O
+encoding	O
+the	O
+amino	O
+-	O
+terminal	O
+17	O
+%	O
+of	O
+apoB	B-GENE
+(	O
+apoB17	B-GENE
+)	O
+was	O
+fused	O
+to	O
+a	O
+cDNA	O
+coding	O
+for	O
+the	O
+last	O
+37	O
+amino	O
+acids	O
+of	O
+decay	B-GENE
+-	I-GENE
+accelerating	I-GENE
+factor	I-GENE
+(	O
+DAF	B-GENE
+)	O
+,	O
+which	O
+contains	O
+the	O
+signal	O
+for	O
+glycosylphosphatidylinositol	O
+anchor	O
+attachment	O
+.	O
+
+Next	O
+,	O
+we	O
+stably	O
+overexpressed	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+Shc	I-GENE
+or	O
+Y317F	B-GENE
+mutant	I-GENE
+Shc	I-GENE
+into	O
+HIRc	O
+cells	O
+.	O
+
+The	O
+small	B-GENE
+GTPase	I-GENE
+Rho	B-GENE
+is	O
+implicated	O
+in	O
+physiological	O
+functions	O
+associated	O
+with	O
+actin	B-GENE
+-	O
+myosin	B-GENE
+filaments	O
+such	O
+as	O
+cytokinesis	O
+,	O
+cell	O
+motility	O
+,	O
+and	O
+smooth	O
+muscle	O
+contraction	O
+.	O
+
+Conversely	O
+,	O
+activation	O
+of	O
+this	O
+signaling	O
+pathway	O
+by	O
+expression	O
+of	O
+a	O
+constitutively	O
+active	O
+MKK1	B-GENE
+mutant	I-GENE
+dramatically	O
+increased	O
+cyclin	B-GENE
+D1	I-GENE
+promoter	O
+activity	O
+and	O
+cyclin	B-GENE
+D1	I-GENE
+protein	I-GENE
+expression	O
+,	O
+in	O
+a	O
+growth	O
+factor	O
+-	O
+independent	O
+manner	O
+.	O
+
+Furthermore	O
+,	O
+upstream	O
+insertion	O
+of	O
+the	O
+GSTP1	B-GENE
+silencer	I-GENE
+element	I-GENE
+failed	O
+to	O
+inhibit	O
+activity	O
+of	O
+a	O
+heterologous	O
+promoter	O
+in	O
+MCF7	O
+cells	O
+.	O
+
+In	O
+order	O
+to	O
+delineate	O
+structural	O
+motifs	O
+regulating	O
+substrate	O
+affinity	O
+and	O
+recognition	O
+for	O
+the	O
+human	B-GENE
+dopamine	I-GENE
+transporter	I-GENE
+(	O
+DAT	B-GENE
+)	O
+,	O
+we	O
+assessed	O
+[	O
+3H	O
+]	O
+dopamine	O
+uptake	O
+kinetics	O
+and	O
+[	O
+3H	O
+]	O
+CFT	O
+binding	O
+characteristics	O
+of	O
+COS	O
+-	O
+7	O
+cells	O
+transiently	O
+expressing	O
+mutant	B-GENE
+DATs	I-GENE
+in	O
+which	O
+the	O
+COOH	O
+terminus	O
+was	O
+truncated	O
+or	O
+substituted	O
+.	O
+
+An	O
+expression	O
+library	O
+was	O
+constructed	O
+by	O
+inserting	O
+5	O
+'	O
+portion	O
+-	O
+enriched	O
+cDNAs	O
+from	O
+phytohemagglutinin	B-GENE
+-	O
+stimulated	O
+peripheral	O
+blood	O
+mononuclear	O
+cells	O
+into	O
+upstream	O
+of	O
+signal	B-GENE
+sequence	I-GENE
+-	I-GENE
+deleted	I-GENE
+CD4	I-GENE
+cDNA	I-GENE
+in	O
+an	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+shuttle	O
+vector	O
+.	O
+
+Radiolabeled	O
+recombinant	B-GENE
+TARC	I-GENE
+specifically	O
+bound	O
+to	O
+T	O
+cell	O
+lines	O
+and	O
+peripheral	O
+T	O
+cells	O
+but	O
+not	O
+to	O
+monocytes	O
+or	O
+granulocytes	O
+.	O
+
+Therefore	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+cis	O
+-	O
+acting	O
+element	O
+,	O
+the	O
+E1	O
+E	O
+-	O
+box	O
+,	O
+located	O
+in	O
+the	O
+GAP	B-GENE
+-	I-GENE
+43	I-GENE
+promoter	O
+region	O
+that	O
+modulates	O
+either	O
+positively	O
+or	O
+negatively	O
+the	O
+expression	O
+of	O
+the	O
+GAP	B-GENE
+-	I-GENE
+43	I-GENE
+gene	I-GENE
+depending	O
+on	O
+which	O
+E	B-GENE
+-	I-GENE
+box	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+occupy	O
+this	O
+site	O
+.	O
+
+Collectively	O
+,	O
+our	O
+findings	O
+demonstrate	O
+that	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+plays	O
+a	O
+key	O
+role	O
+in	O
+controlling	O
+the	O
+basal	O
+and	O
+cAMP	O
+-	O
+stimulated	O
+expression	O
+of	O
+the	O
+StAR	B-GENE
+gene	I-GENE
+.	O
+
+Using	O
+one	O
+of	O
+the	O
+six	O
+fragments	O
+(	O
+CPK3	B-GENE
+-	I-GENE
+8	I-GENE
+)	O
+,	O
+we	O
+isolated	O
+a	O
+2022	B-GENE
+bp	I-GENE
+cDNA	I-GENE
+(	I-GENE
+VrCDPK	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+from	O
+a	O
+Vigna	O
+radiata	O
+lambda	O
+gt11	O
+library	O
+.	O
+
+However	O
+,	O
+in	O
+TF	O
+-	O
+1	O
+cells	O
+grown	O
+on	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+before	O
+starvation	O
+,	O
+CREB	B-GENE
+phosphorylation	O
+was	O
+observed	O
+10	O
+minutes	O
+after	O
+PIXY321	B-GENE
+stimulation	O
+.	O
+
+Workplace	O
+violence	O
+-	O
+-	O
+nurses	O
+at	O
+risk	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+LV	O
+maximum	O
+brightness	O
+and	O
+area	O
+under	O
+the	O
+curve	O
+showed	O
+significant	O
+negative	O
+correlations	O
+(	O
+p	O
+=	O
+<	O
+0	O
+.	O
+004	O
+)	O
+with	O
+the	O
+FIO2	O
+,	O
+while	O
+the	O
+minimum	O
+brightness	O
+showed	O
+a	O
+significant	O
+positive	O
+correlation	O
+(	O
+p	O
+=	O
+<	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+The	O
+results	O
+also	O
+imply	O
+that	O
+the	O
+absence	O
+of	O
+perforin	B-GENE
+expression	O
+in	O
+non	O
+-	O
+cytotoxic	O
+cells	O
+may	O
+be	O
+due	O
+to	O
+the	O
+suppression	O
+of	O
+the	O
+induction	O
+of	O
+the	O
+killer	O
+-	O
+cell	O
+-	O
+specific	O
+trans	O
+-	O
+acting	O
+factor	O
+NF	B-GENE
+-	I-GENE
+P2	I-GENE
+.	O
+
+We	O
+identify	O
+considerable	O
+spatio	O
+-	O
+temporal	O
+similarities	O
+between	O
+reported	O
+expression	O
+patterns	O
+of	O
+Ypr10	B-GENE
+genes	I-GENE
+and	O
+ribonuclease	O
+genes	O
+,	O
+which	O
+,	O
+together	O
+with	O
+the	O
+significant	O
+sequence	O
+similarity	O
+to	O
+the	O
+ginseng	B-GENE
+ribonuclease	I-GENE
+,	O
+support	O
+the	O
+hypothesis	O
+of	O
+a	O
+ribonuclease	O
+function	O
+for	O
+PR	B-GENE
+-	I-GENE
+10	I-GENE
+proteins	I-GENE
+and	O
+allow	O
+the	O
+prediction	O
+of	O
+possible	O
+biological	O
+roles	O
+.	O
+
+The	O
+expression	O
+of	O
+ERV3	B-GENE
+env	I-GENE
+mRNA	I-GENE
+was	O
+found	O
+to	O
+be	O
+differentiation	O
+-	O
+associated	O
+,	O
+with	O
+high	O
+expression	O
+detected	O
+in	O
+the	O
+late	O
+stages	O
+of	O
+monocytic	O
+development	O
+.	O
+
+Initial	O
+estimates	O
+indicate	O
+that	O
+27	O
+,	O
+193	O
+people	O
+are	O
+either	O
+in	O
+receipt	O
+of	O
+or	O
+in	O
+need	O
+of	O
+mental	O
+handicap	O
+services	O
+.	O
+
+It	O
+is	O
+exclusively	O
+observed	O
+in	O
+smooth	O
+muscle	O
+cells	O
+by	O
+Northern	O
+blotting	O
+and	O
+immunohistochemical	O
+analysis	O
+and	O
+therefore	O
+designated	O
+"	B-GENE
+smoothelin	I-GENE
+.	I-GENE
+"	I-GENE
+A	O
+human	O
+smooth	O
+muscle	O
+cDNA	O
+library	O
+was	O
+screened	O
+with	O
+the	O
+monoclonal	B-GENE
+antibody	I-GENE
+R4A	I-GENE
+,	O
+and	O
+a	O
+full	O
+-	O
+size	O
+cDNA	O
+of	O
+the	O
+protein	O
+was	O
+selected	O
+.	O
+
+Concurrent	O
+with	O
+ligand	O
+-	O
+dependent	O
+uptake	O
+,	O
+we	O
+now	O
+show	O
+that	O
+the	O
+receptor	O
+undergoes	O
+ligand	O
+-	O
+induced	O
+ubiquitination	O
+,	O
+suggesting	O
+that	O
+receptor	O
+ubiquitination	O
+may	O
+function	O
+in	O
+the	O
+ligand	O
+-	O
+dependent	O
+endocytosis	O
+of	O
+the	O
+a	B-GENE
+-	I-GENE
+factor	I-GENE
+receptor	I-GENE
+as	O
+well	O
+as	O
+in	O
+its	O
+constitutive	O
+endocytosis	O
+.	O
+
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+nuclear	I-GENE
+protein	I-GENE
+2	I-GENE
+(	O
+EBNA2	B-GENE
+)	O
+binds	O
+to	O
+a	O
+component	O
+of	O
+the	O
+human	O
+SNF	B-GENE
+-	O
+SWI	B-GENE
+complex	O
+,	O
+hSNF5	B-GENE
+/	O
+Ini1	B-GENE
+.	O
+
+Our	O
+studies	O
+also	O
+excluded	O
+the	O
+possibility	O
+that	O
+the	O
+phosphorylation	O
+of	O
+Ser	O
+-	O
+2	O
+,	O
+Ser	O
+-	O
+123	O
+,	O
+or	O
+Ser	O
+-	O
+210	O
+,	O
+had	O
+roles	O
+in	O
+the	O
+trans	O
+-	O
+suppression	O
+activity	O
+of	O
+the	O
+large	B-GENE
+HDAg	I-GENE
+,	O
+in	O
+the	O
+assembly	O
+of	O
+empty	O
+virus	B-GENE
+-	I-GENE
+like	I-GENE
+HDAg	I-GENE
+particle	I-GENE
+,	O
+and	O
+in	O
+the	O
+nuclear	O
+transport	O
+of	O
+HDAgs	B-GENE
+.	O
+
+Homologous	O
+recombination	O
+between	O
+the	O
+Autographa	O
+californica	O
+nuclear	O
+polyhedrosis	O
+virus	O
+(	O
+AcNPV	O
+)	O
+genome	O
+and	O
+a	O
+0	O
+.	O
+6	O
+-	O
+kbp	O
+-	O
+long	O
+DNA	O
+fragment	O
+derived	O
+from	O
+the	O
+putative	O
+DNA	B-GENE
+helicase	I-GENE
+gene	I-GENE
+of	I-GENE
+Bombyx	I-GENE
+mori	I-GENE
+nuclear	I-GENE
+polyhedrosis	I-GENE
+virus	I-GENE
+generates	O
+eh2	O
+-	O
+AcNPV	O
+,	O
+an	O
+expanded	O
+-	O
+host	O
+-	O
+range	O
+AcNPV	O
+mutant	O
+(	O
+S	O
+.	O
+
+The	O
+data	O
+further	O
+indicate	O
+that	O
+the	O
+IL	B-GENE
+-	I-GENE
+7R	I-GENE
+alpha	I-GENE
+chains	I-GENE
+are	O
+directly	O
+involved	O
+in	O
+the	O
+activation	O
+of	O
+JAKs	B-GENE
+and	O
+STATs	B-GENE
+and	O
+have	O
+a	O
+major	O
+role	O
+in	O
+proliferative	O
+signaling	O
+in	O
+precursor	O
+B	O
+cells	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+potency	O
+of	O
+Dacarbacine	O
+in	O
+the	O
+treatment	O
+of	O
+carcinoid	O
+tumors	O
+seems	O
+to	O
+be	O
+underestimated	O
+up	O
+to	O
+now	O
+.	O
+
+5	O
+)	O
+We	O
+'	O
+ve	O
+noticed	O
+that	O
+the	O
+mean	O
+value	O
+of	O
+the	O
+cost	O
+for	O
+episode	O
+of	O
+pnx	O
+s	O
+.	O
+in	O
+class	O
+A	O
+was	O
+more	O
+than	O
+15	O
+%	O
+compared	O
+to	O
+class	O
+B	O
+and	O
+the	O
+cost	O
+for	O
+patient	O
+in	O
+class	O
+A	O
+was	O
+nearly	O
+double	O
+than	O
+in	O
+class	O
+B	O
+.	O
+
+Cbl	B-GENE
+constitutively	O
+interacts	O
+with	O
+the	O
+SH3	B-GENE
+domains	I-GENE
+of	O
+Grb2	B-GENE
+,	O
+with	O
+a	O
+preference	O
+for	O
+the	O
+amino	O
+-	O
+terminal	O
+domain	O
+,	O
+and	O
+is	O
+in	O
+this	O
+way	O
+recruited	O
+to	O
+Shc	B-GENE
+upon	O
+BCR	B-GENE
+stimulation	O
+.	O
+
+Activation	O
+mediated	O
+by	O
+Cat8p	B-GENE
+was	O
+no	O
+longer	O
+detectable	O
+in	O
+a	O
+cat1	B-GENE
+mutant	I-GENE
+.	O
+
+Treatment	O
+is	O
+instituted	O
+with	O
+prednisone	O
+and	O
+cyclophosphamide	O
+.	O
+
+Laboratory	O
+evaluation	O
+was	O
+normal	O
+,	O
+and	O
+neuroimaging	O
+failed	O
+to	O
+confirm	O
+obstruction	O
+of	O
+venous	O
+or	O
+lymphatic	O
+drainage	O
+.	O
+
+Microcomputer	O
+management	O
+of	O
+chronic	O
+hepatitis	O
+B	O
+virus	O
+asymptomatic	O
+patients	O
+
+While	O
+fusion	O
+to	O
+the	O
+N	O
+-	O
+terminus	O
+required	O
+a	O
+linker	O
+to	O
+become	O
+surface	O
+accessible	O
+,	O
+both	O
+fusion	O
+to	O
+the	O
+N	O
+-	O
+terminus	O
+and	O
+to	O
+the	O
+C	O
+-	O
+terminus	O
+was	O
+compatible	O
+with	O
+particle	O
+assembly	O
+and	O
+preserved	O
+the	O
+native	O
+antigenicity	O
+and	O
+immunogenicity	O
+of	O
+HBcAg	B-GENE
+.	O
+
+The	O
+standard	O
+dosage	O
+of	O
+anti	B-GENE
+-	I-GENE
+D	I-GENE
+currently	O
+given	O
+at	O
+all	O
+gestational	O
+ages	O
+is	O
+1	O
+ampoule	O
+containing	O
+125	O
+micrograms	O
+of	O
+anti	B-GENE
+-	I-GENE
+D	I-GENE
+.	O
+
+We	O
+report	O
+here	O
+the	O
+molecular	O
+cloning	O
+of	O
+a	O
+putative	O
+adhesive	O
+molecule	O
+from	O
+P	O
+.	O
+falciparum	O
+that	O
+shares	O
+both	O
+sequence	O
+and	O
+structural	O
+similarities	O
+with	O
+a	O
+sporozoite	O
+surface	O
+molecule	O
+from	O
+Plasmodium	O
+termed	O
+the	O
+thrombospondin	B-GENE
+-	I-GENE
+related	I-GENE
+anonymous	I-GENE
+protein	I-GENE
+(	O
+TRAP	B-GENE
+)	O
+and	O
+,	O
+to	O
+a	O
+lesser	O
+extent	O
+,	O
+with	O
+the	O
+circumsporozoite	B-GENE
+(	I-GENE
+CS	I-GENE
+)	I-GENE
+protein	I-GENE
+.	O
+
+There	O
+are	O
+no	O
+introns	O
+within	O
+the	O
+gene	O
+,	O
+which	O
+contains	O
+a	O
+9360	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+and	O
+encodes	O
+a	O
+377	O
+-	O
+kDa	O
+protein	O
+.	O
+
+METHODS	O
+:	O
+DSF	O
+was	O
+instilled	O
+in	O
+one	O
+eye	O
+chosen	O
+at	O
+random	O
+and	O
+CF	O
+in	O
+the	O
+fellow	O
+eye	O
+of	O
+13	O
+normal	O
+subjects	O
+and	O
+in	O
+13	O
+patients	O
+with	O
+KCS	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+results	O
+demonstrate	O
+that	O
+at	O
+the	O
+site	O
+of	O
+lumbar	O
+disc	O
+herniation	O
+,	O
+inflammatory	O
+cytokines	O
+such	O
+as	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+are	O
+produced	O
+,	O
+which	O
+increases	O
+prostaglandin	O
+E2	O
+production	O
+.	O
+
+The	O
+predominant	O
+sensitizing	O
+allergens	O
+in	O
+Swedish	O
+asthmatic	O
+children	O
+are	O
+furred	O
+pet	O
+animals	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+that	O
+distinct	O
+cytoplasmic	O
+domains	O
+of	O
+these	O
+cytokine	O
+receptors	O
+elicit	O
+convergent	O
+signaling	O
+pathways	O
+and	O
+provide	O
+evidence	O
+that	O
+beta	B-GENE
+c	I-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+2R	I-GENE
+beta	I-GENE
+function	O
+as	O
+a	O
+complete	O
+signal	O
+transducer	O
+.	O
+
+In	O
+addition	O
+,	O
+they	O
+display	O
+common	O
+features	O
+that	O
+make	O
+them	O
+strikingly	O
+related	O
+to	O
+snoRNA	B-GENE
+U14	I-GENE
+.	O
+
+U24	B-GENE
+has	O
+two	O
+separate	O
+12	O
+nt	O
+long	O
+complementarities	O
+to	O
+a	O
+highly	O
+conserved	O
+tract	O
+of	O
+28S	B-GENE
+rRNA	I-GENE
+.	O
+
+This	O
+complex	O
+interacts	O
+at	O
+the	O
+GTPase	B-GENE
+domain	I-GENE
+in	O
+the	O
+large	O
+subunit	O
+rRNA	O
+,	O
+overlapping	O
+the	O
+binding	O
+site	O
+of	O
+the	O
+protein	B-GENE
+L11	I-GENE
+-	I-GENE
+like	I-GENE
+eukaryotic	I-GENE
+counterpart	I-GENE
+(	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+protein	I-GENE
+L15	I-GENE
+and	O
+mammalian	B-GENE
+protein	I-GENE
+L12	I-GENE
+)	O
+.	O
+
+Chromatin	O
+repression	O
+of	O
+these	O
+replacement	O
+genes	O
+would	O
+be	O
+avoided	O
+,	O
+consistent	O
+with	O
+the	O
+high	O
+,	O
+constitutive	O
+expression	O
+of	O
+replacement	O
+H3	B-GENE
+histone	I-GENE
+genes	I-GENE
+in	O
+plants	O
+.	O
+
+This	O
+transition	O
+is	O
+regulated	O
+positively	O
+by	O
+G1	B-GENE
+-	I-GENE
+specific	I-GENE
+cyclin	I-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+(	O
+cdks	B-GENE
+)	O
+and	O
+negatively	O
+by	O
+the	O
+product	O
+of	O
+the	O
+retinoblastoma	B-GENE
+tumour	I-GENE
+suppressor	I-GENE
+gene	I-GENE
+,	O
+pRb	B-GENE
+.	O
+
+To	O
+derive	O
+quantitative	O
+concentration	O
+changes	O
+from	O
+measurements	O
+of	O
+light	O
+attenuation	O
+,	O
+the	O
+optical	O
+path	O
+length	O
+must	O
+be	O
+known	O
+.	O
+
+STUDY	O
+DESIGN	O
+.	O
+
+Following	O
+the	O
+injection	O
+of	O
+PGF2	O
+alpha	O
+,	O
+heifers	O
+were	O
+observed	O
+visually	O
+for	O
+signs	O
+of	O
+estrus	O
+at	O
+0730	O
+and	O
+1630	O
+(	O
+45	O
+min	O
+each	O
+)	O
+.	O
+
+Differential	O
+activation	O
+of	O
+the	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+,	O
+Jun	B-GENE
+kinase	I-GENE
+and	O
+Janus	B-GENE
+kinase	I-GENE
+-	O
+Stat	B-GENE
+pathways	O
+by	O
+oncostatin	B-GENE
+M	I-GENE
+and	O
+basic	B-GENE
+fibroblast	I-GENE
+growth	I-GENE
+factor	I-GENE
+in	O
+AIDS	O
+-	O
+derived	O
+Kaposi	O
+'	O
+s	O
+sarcoma	O
+cells	O
+.	O
+
+There	O
+is	O
+general	O
+agreement	O
+that	O
+the	O
+hepatitis	O
+C	O
+virus	O
+is	O
+efficiently	O
+transmitted	O
+parenterally	O
+,	O
+while	O
+data	O
+on	O
+viral	O
+transmission	O
+from	O
+mothers	O
+to	O
+babies	O
+or	O
+by	O
+sexual	O
+or	O
+non	O
+-	O
+sexual	O
+household	O
+contact	O
+are	O
+conflicting	O
+.	O
+
+Ten	O
+weeks	O
+after	O
+reconstruction	O
+,	O
+the	O
+regenerating	O
+nerves	O
+already	O
+resembled	O
+normal	O
+nerves	O
+.	O
+
+The	O
+distribution	O
+and	O
+organization	O
+of	O
+projections	O
+from	O
+the	O
+spinal	O
+cervical	O
+enlargement	O
+to	O
+subnucleus	O
+reticularis	O
+dorsalis	O
+(	O
+SRD	O
+)	O
+and	O
+the	O
+neighbouring	O
+Cuneate	O
+nucleus	O
+(	O
+Cu	O
+)	O
+area	O
+was	O
+studied	O
+in	O
+the	O
+rat	O
+by	O
+using	O
+microinjections	O
+of	O
+Phaseolus	B-GENE
+vulgaris	I-GENE
+leucoagglutinin	I-GENE
+(	O
+PHA	B-GENE
+-	I-GENE
+L	I-GENE
+)	O
+into	O
+different	O
+laminae	O
+around	O
+the	O
+C7	O
+level	O
+.	O
+
+The	O
+levels	O
+of	O
+fibrinogen	B-GENE
+as	O
+well	O
+as	O
+antithrombin	B-GENE
+III	I-GENE
+(	O
+ATIII	B-GENE
+)	O
+and	O
+heparin	B-GENE
+cofactor	I-GENE
+II	I-GENE
+(	O
+HCII	B-GENE
+)	O
+activities	O
+were	O
+steadily	O
+increased	O
+in	O
+loop	O
+-	O
+bearing	O
+animals	O
+.	O
+
+Amplification	O
+and	O
+overexpression	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+erbB	I-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+in	O
+21MT	O
+-	O
+2	O
+and	O
+21MT	O
+-	O
+1	O
+human	O
+breast	O
+carcinoma	O
+cells	O
+results	O
+in	O
+progressively	O
+elevated	O
+levels	O
+of	O
+constitutively	O
+tyrosine	B-GENE
+-	I-GENE
+phosphorylated	I-GENE
+p185erbB	I-GENE
+-	I-GENE
+2	I-GENE
+and	O
+is	O
+associated	O
+with	O
+progressive	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+IGF	B-GENE
+)	O
+and	O
+combined	O
+IGF	B-GENE
+/	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+EGF	B-GENE
+)	O
+independence	O
+in	O
+culture	O
+.	O
+
+Facioscapulohumeral	O
+muscular	O
+dystrophy	O
+(	O
+FSHD	O
+)	O
+is	O
+an	O
+autosomal	O
+dominant	O
+,	O
+neuromuscular	O
+disorder	O
+characterized	O
+by	O
+progressive	O
+weakness	O
+of	O
+muscles	O
+in	O
+the	O
+face	O
+,	O
+shoulder	O
+and	O
+upper	O
+arm	O
+.	O
+
+The	O
+mature	O
+chromosome	O
+4	O
+FRG1	B-GENE
+transcript	I-GENE
+is	O
+1042	O
+bp	O
+in	O
+length	O
+and	O
+contains	O
+nine	O
+exons	O
+which	O
+encode	O
+a	O
+putative	O
+protein	O
+of	O
+258	O
+amino	O
+acid	O
+residues	O
+.	O
+
+Patients	O
+who	O
+have	O
+undergone	O
+thyroidectomy	O
+for	O
+thyroid	O
+carcinoma	O
+are	O
+frequently	O
+subjected	O
+to	O
+periods	O
+of	O
+induced	O
+severe	O
+hypothyroidism	O
+in	O
+preparation	O
+for	O
+131I	O
+whole	O
+body	O
+scanning	O
+and	O
+measurement	O
+of	O
+serum	O
+TG	B-GENE
+.	O
+
+Full	O
+thyroid	O
+function	O
+testing	O
+was	O
+performed	O
+on	O
+600	O
+randomly	O
+selected	O
+samples	O
+with	O
+normal	O
+TSH	B-GENE
+values	O
+and	O
+also	O
+on	O
+subjects	O
+with	O
+abnormal	O
+TSH	B-GENE
+levels	O
+.	O
+
+In	O
+a	O
+third	O
+experiment	O
+,	O
+crossover	O
+AM	O
+between	O
+dissimilar	O
+textures	O
+was	O
+investigated	O
+,	O
+and	O
+it	O
+was	O
+found	O
+that	O
+the	O
+more	O
+salient	O
+textures	O
+carried	O
+the	O
+AM	O
+.	O
+
+The	O
+relative	O
+tumor	O
+FDG	O
+-	O
+uptake	O
+(	O
+Q	O
+-	O
+MRGlu	O
+)	O
+(	O
+tumor	O
+/	O
+contralateral	O
+cortex	O
+)	O
+of	O
+all	O
+meningiomas	O
+was	O
+calculated	O
+with	O
+0	O
+.	O
+73	O
++	O
+/	O
+-	O
+0	O
+.	O
+37	O
+(	O
+0	O
+.	O
+24	O
+-	O
+1	O
+.	O
+79	O
+)	O
+.	O
+
+Zatebradine	O
+weakly	O
+depressed	O
+the	O
+ectopic	O
+ventricular	O
+rate	O
+but	O
+not	O
+the	O
+arrhythmic	O
+ratio	O
+of	O
+the	O
+ventricular	O
+arrhythmias	O
+induced	O
+by	O
+two	O
+-	O
+stage	O
+coronary	O
+ligation	O
+24	O
+h	O
+after	O
+the	O
+ligation	O
+in	O
+conscious	O
+dogs	O
+.	O
+
+Catha	O
+edulis	O
+,	O
+a	O
+plant	O
+that	O
+has	O
+amphetamine	O
+effects	O
+.	O
+
+The	O
+predicted	O
+protein	O
+,	O
+Seb1p	B-GENE
+,	O
+consists	O
+of	O
+82	O
+amino	O
+acids	O
+and	O
+contains	O
+one	O
+potential	O
+membrane	O
+-	O
+spanning	O
+region	O
+at	O
+the	O
+C	O
+-	O
+terminus	O
+but	O
+no	O
+N	O
+-	O
+terminal	O
+signal	O
+sequence	O
+.	O
+
+The	O
+SEB1	B-GENE
+homologue	O
+thus	O
+isolated	O
+,	O
+SEB2	B-GENE
+,	O
+encodes	O
+a	O
+protein	O
+53	O
+%	O
+identical	O
+to	O
+Seb1p	B-GENE
+.	O
+
+Nonetheless	O
+,	O
+that	O
+ventricular	O
+afferents	O
+,	O
+in	O
+certain	O
+special	O
+settings	O
+,	O
+are	O
+able	O
+to	O
+induce	O
+e	O
+.	O
+g	O
+.	O
+generalised	O
+vasodilation	O
+and	O
+hypotension	O
+cannot	O
+be	O
+excluded	O
+.	O
+
+Large	O
+ones	O
+were	O
+similar	O
+in	O
+size	O
+to	O
+the	O
+main	O
+lobe	O
+and	O
+small	O
+ones	O
+were	O
+approximately	O
+1	O
+/	O
+4	O
+of	O
+the	O
+length	O
+of	O
+the	O
+main	O
+lobe	O
+.	O
+
+Fragments	O
+and	O
+analogs	O
+of	O
+the	O
+hormone	O
+ACTH	B-GENE
+were	O
+previously	O
+shown	O
+to	O
+have	O
+beneficial	O
+effect	O
+on	O
+the	O
+outcome	O
+of	O
+head	O
+injury	O
+,	O
+while	O
+elevated	O
+levels	O
+of	O
+corticosterone	O
+(	O
+CS	O
+)	O
+exacerbate	O
+it	O
+.	O
+
+Fifty	O
+-	O
+one	O
+patients	O
+with	O
+primary	O
+refractory	O
+or	O
+relapsed	O
+malignant	O
+lymphoma	O
+(	O
+47	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphoma	O
+and	O
+four	O
+Hodgkin	O
+'	O
+s	O
+disease	O
+)	O
+were	O
+treated	O
+with	O
+a	O
+new	O
+chemotherapeutic	O
+regimen	O
+(	O
+cisplatinum	O
+,	O
+methyl	O
+GAG	O
+,	O
+bleomocyin	O
+,	O
+methyl	O
+prednisolon	O
+)	O
+.	O
+
+With	O
+the	O
+increasing	O
+use	O
+of	O
+ACE	B-GENE
+inhibitors	O
+,	O
+the	O
+incidence	O
+of	O
+rare	O
+adverse	O
+effects	O
+such	O
+as	O
+potentially	O
+lethal	O
+pancreatitis	O
+is	O
+likely	O
+to	O
+increase	O
+.	O
+
+In	O
+3	O
+treatments	O
+the	O
+diet	O
+was	O
+supplemented	O
+with	O
+0	O
+,	O
+100	O
+and	O
+150	O
+mg	O
+probiotic	O
+/	O
+kg	O
+food	O
+.	O
+
+Low	O
+-	O
+dose	O
+aspirin	O
+and	O
+recurrent	O
+miscarriage	O
+.	O
+
+Protein	O
+films	O
+are	O
+distinctly	O
+different	O
+in	O
+mechanical	O
+profiles	O
+from	O
+those	O
+films	O
+made	O
+of	O
+other	O
+materials	O
+.	O
+
+Furthermore	O
+,	O
+cpxA	B-GENE
+*	I-GENE
+mutations	O
+suppress	O
+the	O
+toxicity	O
+conferred	O
+by	O
+the	O
+LamB	B-GENE
+-	O
+LacZ	B-GENE
+hybrid	O
+protein	O
+,	O
+which	O
+exerts	O
+its	O
+effects	O
+in	O
+the	O
+cytoplasm	O
+,	O
+sequestered	O
+from	O
+DegP	B-GENE
+.	O
+
+The	O
+PI3K	B-GENE
+_	I-GENE
+68D	I-GENE
+cDNA	I-GENE
+encodes	O
+a	O
+protein	O
+of	O
+210	O
+kDa	O
+,	O
+which	O
+lacks	O
+sequences	O
+implicated	O
+in	O
+linking	O
+p110	B-GENE
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinases	I-GENE
+to	O
+p85	B-GENE
+adaptor	I-GENE
+proteins	I-GENE
+,	O
+but	O
+contains	O
+an	O
+amino	O
+-	O
+terminal	O
+proline	O
+-	O
+rich	O
+sequence	O
+,	O
+which	O
+could	O
+bind	O
+to	O
+SH3	B-GENE
+domains	I-GENE
+,	O
+and	O
+a	O
+carboxy	O
+-	O
+terminal	O
+C2	B-GENE
+domain	O
+.	O
+
+AIMS	O
+/	O
+METHODS	O
+:	O
+Reticuloendothelial	O
+system	O
+function	O
+,	O
+as	O
+assessed	O
+by	O
+clearance	O
+of	O
+radiolabelled	O
+bacteria	O
+,	O
+was	O
+evaluated	O
+in	O
+acute	O
+liver	O
+injury	O
+induced	O
+by	O
+D	O
+-	O
+galactosamine	O
+in	O
+rats	O
+,	O
+and	O
+compared	O
+with	O
+that	O
+after	O
+70	O
+%	O
+liver	O
+resection	O
+model	O
+.	O
+
+Our	O
+laboratory	O
+and	O
+others	O
+have	O
+shown	O
+alternative	O
+splicing	O
+of	O
+up	O
+to	O
+ten	O
+exons	O
+at	O
+a	O
+discrete	O
+extracellular	O
+site	O
+to	O
+be	O
+primarily	O
+responsible	O
+for	O
+the	O
+generation	O
+of	O
+CD44	B-GENE
+variant	I-GENE
+(	O
+CD44v	B-GENE
+)	O
+isoforms	O
+.	O
+
+Study	O
+groups	O
+were	O
+control	O
+,	O
+and	O
+those	O
+treated	O
+with	O
+the	O
+alpha1	B-GENE
+-	I-GENE
+adrenoceptor	I-GENE
+-	I-GENE
+subtype	I-GENE
+blockers	O
+WB4101	O
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+or	O
+chloroethylclonidine	O
+(	O
+1	O
+.	O
+9	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+.	O
+
+This	O
+caused	O
+severe	O
+cortical	O
+damage	O
+and	O
+neuronal	O
+loss	O
+in	O
+hippocampus	O
+subfields	O
+CA1	O
+,	O
+CA3	O
+,	O
+and	O
+hilus	O
+.	O
+
+The	O
+occurrence	O
+of	O
+multiple	O
+malignancy	O
+was	O
+studied	O
+in	O
+674	O
+patients	O
+with	O
+hematologic	O
+malignancies	O
+who	O
+were	O
+admitted	O
+to	O
+this	O
+department	O
+during	O
+the	O
+past	O
+10	O
+years	O
+.	O
+
+The	O
+upTRE	O
+binds	O
+more	O
+T3R	B-GENE
+homodimers	I-GENE
+and	O
+less	O
+T3R	B-GENE
+-	O
+RXR	B-GENE
+heterodimers	O
+than	O
+the	O
+dnTRE	O
+,	O
+and	O
+T3	O
+more	O
+readily	O
+facilitates	O
+heterodimer	O
+binding	O
+to	O
+the	O
+dn	O
+-	O
+than	O
+to	O
+the	O
+upTRE	O
+.	O
+
+Transcriptional	O
+control	O
+of	O
+a	O
+nuclear	O
+gene	O
+encoding	O
+a	O
+mitochondrial	O
+fatty	O
+acid	O
+oxidation	O
+enzyme	O
+in	O
+transgenic	O
+mice	O
+:	O
+role	O
+for	O
+nuclear	O
+receptors	O
+in	O
+cardiac	O
+and	O
+brown	O
+adipose	O
+expression	O
+.	O
+
+Hoeben	O
+,	O
+F	O
+.	O
+J	O
+.	O
+
+Moreover	O
+,	O
+glucan	B-GENE
+synthase	I-GENE
+activity	O
+,	O
+which	O
+is	O
+activated	O
+by	O
+Rho1p	B-GENE
+,	O
+was	O
+significantly	O
+reduced	O
+in	O
+the	O
+deltabem4	B-GENE
+mutant	I-GENE
+.	O
+
+In	O
+gel	O
+retardation	O
+assays	O
+,	O
+an	O
+RCS	O
+cell	O
+-	O
+specific	O
+protein	O
+and	O
+another	O
+closely	O
+related	O
+protein	O
+expressed	O
+only	O
+in	O
+RCS	O
+cells	O
+and	O
+primary	O
+chondrocytes	O
+bound	O
+to	O
+a	O
+10	O
+-	O
+bp	O
+sequence	O
+within	O
+the	O
+18	O
+-	O
+mer	O
+.	O
+
+Two	O
+classes	O
+of	O
+Xanthomonas	O
+pathogens	O
+evading	O
+Bs2	O
+host	O
+resistance	O
+and	O
+displaying	O
+reduced	O
+fitness	O
+were	O
+found	O
+to	O
+be	O
+specifically	O
+mutated	O
+in	O
+avrBs2	B-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+characterization	O
+of	O
+the	O
+promoter	O
+region	O
+should	O
+help	O
+to	O
+define	O
+regulatory	O
+elements	O
+that	O
+control	O
+neuron	O
+-	O
+specific	O
+and	O
+developmental	O
+expression	O
+of	O
+the	O
+MAP1B	B-GENE
+gene	I-GENE
+.	O
+
+Mutants	O
+lacking	O
+the	O
+3	O
+'	O
+stem	O
+-	O
+loop	O
+exhibited	O
+a	O
+75	O
+%	O
+reduction	O
+in	O
+the	O
+level	O
+of	O
+psaB	B-GENE
+mRNA	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+was	O
+highly	O
+conserved	O
+across	O
+the	O
+wide	O
+range	O
+of	O
+eukaryotes	O
+(	O
+vertebrates	O
+,	O
+invertebrates	O
+,	O
+fungi	O
+,	O
+plants	O
+and	O
+protozoa	O
+)	O
+in	O
+which	O
+this	O
+gene	O
+has	O
+now	O
+been	O
+identified	O
+.	O
+
+Semidominant	O
+mutations	O
+in	O
+the	O
+yeast	B-GENE
+Rad51	I-GENE
+protein	I-GENE
+and	O
+their	O
+relationships	O
+with	O
+the	O
+Srs2	B-GENE
+helicase	I-GENE
+.	O
+
+Alterations	O
+of	O
+the	O
+5q23	O
+-	O
+q31	O
+interval	O
+are	O
+frequently	O
+observed	O
+in	O
+myelodysplasia	O
+and	O
+myeloid	O
+leukemia	O
+.	O
+
+Previous	O
+studies	O
+have	O
+suggested	O
+that	O
+the	O
+616	O
+amino	O
+acid	O
+,	O
+70	B-GENE
+-	I-GENE
+kDa	I-GENE
+subunit	I-GENE
+of	I-GENE
+RPA	I-GENE
+(	O
+RPA	B-GENE
+70	I-GENE
+)	O
+is	O
+composed	O
+of	O
+multiple	O
+structural	O
+/	O
+functional	O
+domains	O
+.	O
+
+Neurons	O
+were	O
+held	O
+at	O
+-	O
+67	O
+mV	O
+to	O
+equate	O
+voltage	O
+-	O
+dependent	O
+effects	O
+.	O
+
+This	O
+site	O
+acts	O
+as	O
+a	O
+negative	O
+element	O
+when	O
+transferred	O
+to	O
+the	O
+thymidine	B-GENE
+kinase	I-GENE
+promoter	I-GENE
+,	O
+but	O
+does	O
+not	O
+confer	O
+inducibility	O
+.	O
+
+The	O
+extent	O
+of	O
+the	O
+fbpA	B-GENE
+operator	I-GENE
+sequence	I-GENE
+(	I-GENE
+42	I-GENE
+bp	I-GENE
+)	I-GENE
+,	O
+as	O
+defined	O
+by	O
+our	O
+footprinting	O
+analysis	O
+,	O
+would	O
+suggest	O
+the	O
+binding	O
+of	O
+two	O
+Fur	B-GENE
+repressor	I-GENE
+dimers	I-GENE
+.	O
+
+The	O
+structural	O
+similarity	O
+between	O
+Vav	B-GENE
+and	O
+other	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factors	I-GENE
+for	O
+small	B-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+,	O
+together	O
+with	O
+the	O
+recent	O
+identification	O
+of	O
+biochemical	O
+routes	O
+specific	O
+for	O
+members	O
+of	O
+the	O
+Ras	B-GENE
+and	O
+Rho	B-GENE
+family	I-GENE
+of	O
+GTPases	B-GENE
+,	O
+prompted	O
+us	O
+to	O
+explore	O
+whether	O
+MAPK	B-GENE
+or	O
+JNK	B-GENE
+are	O
+downstream	O
+components	O
+of	O
+the	O
+Vav	B-GENE
+signaling	O
+pathways	O
+.	O
+
+CONCLUSION	O
+:	O
+Twice	O
+daily	O
+treatment	O
+with	O
+inhaled	O
+fluticasone	O
+propionate	O
+50	O
+micrograms	O
+or	O
+100	O
+micrograms	O
+was	O
+significantly	O
+more	O
+effective	O
+than	O
+theophylline	O
+in	O
+the	O
+treatment	O
+of	O
+mild	O
+-	O
+to	O
+-	O
+moderate	O
+asthma	O
+.	O
+
+Our	O
+results	O
+support	O
+a	O
+model	O
+where	O
+both	O
+E2F	B-GENE
+-	O
+and	O
+CDE	O
+-	O
+mediated	O
+repression	O
+,	O
+acting	O
+at	O
+different	O
+stages	O
+in	O
+the	O
+cell	O
+cycle	O
+,	O
+are	O
+dependent	O
+on	O
+promoter	O
+-	O
+specific	O
+CHR	O
+elements	O
+.	O
+
+The	O
+cDNA	O
+clone	O
+was	O
+used	O
+as	O
+a	O
+homologous	O
+probe	O
+to	O
+isolate	O
+a	O
+truncated	O
+genomic	O
+clone	O
+encoding	O
+H2A1	B-GENE
+.	O
+
+Comparison	O
+of	O
+the	O
+deduced	O
+amino	O
+acid	O
+sequences	O
+with	O
+protein	O
+sequences	O
+of	O
+T	O
+.	O
+pyriformis	O
+H2As	B-GENE
+showed	O
+only	O
+two	O
+and	O
+three	O
+differences	O
+respectively	O
+,	O
+in	O
+a	O
+total	O
+of	O
+137	O
+amino	O
+acids	O
+for	O
+H2A1	B-GENE
+,	O
+and	O
+132	O
+amino	O
+acids	O
+for	O
+H2A2	B-GENE
+,	O
+indicating	O
+the	O
+two	O
+genes	O
+arose	O
+before	O
+the	O
+divergence	O
+of	O
+these	O
+two	O
+species	O
+.	O
+
+Cognitive	O
+visual	O
+dysfunction	O
+in	O
+a	O
+child	O
+with	O
+cerebral	O
+damage	O
+.	O
+
+Interaction	O
+was	O
+apparently	O
+determined	O
+by	O
+the	O
+N	O
+-	O
+terminal	O
+splice	O
+region	O
+of	O
+RPDE	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+as	O
+the	O
+PDE4A	B-GENE
+splice	O
+variant	O
+RPDE	B-GENE
+-	I-GENE
+39	I-GENE
+,	O
+which	O
+differs	O
+from	O
+RPDE	B-GENE
+-	I-GENE
+6	I-GENE
+at	O
+the	O
+extreme	O
+N	O
+-	O
+terminus	O
+,	O
+failed	O
+to	O
+associate	O
+with	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+-	O
+SH3	B-GENE
+;	O
+met26RD1	B-GENE
+(	O
+where	O
+RD1	B-GENE
+is	O
+rat	B-GENE
+'	I-GENE
+dunc	I-GENE
+-	I-GENE
+like	I-GENE
+'	I-GENE
+PDE	I-GENE
+)	O
+,	O
+which	O
+has	O
+the	O
+N	O
+-	O
+terminal	O
+splice	O
+region	O
+deleted	O
+,	O
+failed	O
+to	O
+associate	O
+with	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+-	O
+SH3	B-GENE
+,	O
+and	O
+the	O
+association	O
+of	O
+RPDE	B-GENE
+-	I-GENE
+6	I-GENE
+and	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+-	O
+SH3	B-GENE
+was	O
+blocked	O
+by	O
+a	O
+fusion	O
+protein	O
+formed	O
+from	O
+the	O
+N	O
+-	O
+terminal	O
+splice	O
+region	O
+.	O
+
+Potentially	O
+load	O
+-	O
+insensitive	O
+measures	O
+of	O
+ventricular	O
+performance	O
+were	O
+therefore	O
+evaluated	O
+in	O
+10	O
+open	O
+-	O
+and	O
+closed	O
+-	O
+chested	O
+,	O
+anesthetized	O
+rabbits	O
+.	O
+
+Large	O
+strain	O
+differences	O
+were	O
+found	O
+for	O
+all	O
+variables	O
+recorded	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+proportion	O
+of	O
+attacking	O
+males	O
+,	O
+the	O
+time	O
+spent	O
+in	O
+the	O
+brightly	O
+lit	O
+box	O
+,	O
+and	O
+the	O
+number	O
+of	O
+transitions	O
+between	O
+the	O
+lit	O
+and	O
+the	O
+dark	O
+boxes	O
+.	O
+
+It	O
+is	O
+the	O
+oxidation	O
+peak	O
+of	O
+this	O
+product	O
+,	O
+arising	O
+in	O
+acidic	O
+media	O
+at	O
+0	O
+.	O
+42	O
+V	O
+,	O
+which	O
+was	O
+analysed	O
+using	O
+DPV	O
+,	O
+again	O
+following	O
+the	O
+accumulation	O
+of	O
+clenbuterol	O
+at	O
+the	O
+Nafion	O
+-	O
+modified	O
+CPE	O
+.	O
+
+Phenylephrine	O
+is	O
+a	O
+pure	O
+alpha	B-GENE
+-	I-GENE
+1	I-GENE
+adrenoreceptor	I-GENE
+agonist	O
+known	O
+to	O
+produce	O
+marked	O
+systemic	O
+vasoconstriction	O
+and	O
+associated	O
+hypertension	O
+with	O
+occasional	O
+profound	O
+reflex	O
+bradycardia	O
+.	O
+
+The	O
+expression	O
+of	O
+the	O
+first	O
+two	O
+genes	O
+located	O
+in	O
+this	O
+unit	O
+(	O
+c	B-GENE
+-	I-GENE
+gvpD	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+gvpE	I-GENE
+)	O
+was	O
+also	O
+monitored	O
+by	O
+Western	O
+blot	O
+(	O
+immunoblot	O
+)	O
+analyses	O
+using	O
+antisera	O
+raised	O
+against	O
+these	O
+proteins	O
+synthesized	O
+in	O
+Escherichia	O
+coli	O
+.	O
+
+One	O
+unit	O
+encodes	O
+traA	B-GENE
+,	O
+traF	B-GENE
+,	O
+and	O
+traB	B-GENE
+,	O
+while	O
+the	O
+second	O
+encodes	O
+traC	B-GENE
+,	O
+traD	B-GENE
+,	O
+and	O
+traG	B-GENE
+.	O
+
+A	O
+.	O
+
+In	O
+an	O
+effort	O
+to	O
+isolate	O
+genes	O
+with	O
+down	O
+-	O
+regulated	O
+expression	O
+at	O
+the	O
+mRNA	O
+level	O
+during	O
+oncogenic	O
+transformation	O
+of	O
+human	O
+mammary	O
+epithelial	O
+cells	O
+(	O
+MECs	O
+)	O
+,	O
+we	O
+performed	O
+subtractive	O
+hybridization	O
+between	O
+normal	O
+MEC	O
+strain	O
+76N	O
+and	O
+its	O
+radiation	O
+-	O
+transformed	O
+tumorigenic	O
+derivative	O
+76R	O
+-	O
+30	O
+.	O
+
+CASE	O
+REPORT	O
+:	O
+Referred	O
+because	O
+of	O
+a	O
+right	O
+corneal	O
+perforation	O
+with	O
+cellular	O
+reaction	O
+in	O
+anterior	O
+chamber	O
+,	O
+a	O
+patient	O
+was	O
+sutured	O
+and	O
+treated	O
+with	O
+a	O
+single	O
+intravitreal	O
+injection	O
+of	O
+0	O
+.	O
+2	O
+ml	O
+(	O
+1	O
+mg	O
+)	O
+Amikacin	O
+and	O
+0	O
+.	O
+2	O
+ml	O
+(	O
+1	O
+mg	O
+)	O
+Vancomycin	O
+.	O
+
+The	O
+P	B-GENE
+-	I-GENE
+wr	I-GENE
+and	O
+P	B-GENE
+-	I-GENE
+rr	I-GENE
+cDNA	I-GENE
+sequences	I-GENE
+are	O
+very	O
+similar	O
+in	O
+their	O
+5	O
+'	O
+regions	O
+.	O
+
+Because	O
+the	O
+hcf109	B-GENE
+locus	I-GENE
+was	O
+mapped	O
+at	O
+a	O
+distance	O
+<	O
+0	O
+.	O
+1	O
+centimorgans	O
+from	O
+the	O
+phytochrome	B-GENE
+C	I-GENE
+gene	I-GENE
+,	O
+its	O
+molecular	O
+characterization	O
+by	O
+positional	O
+cloning	O
+is	O
+possible	O
+.	O
+
+The	O
+human	B-GENE
+MSH	I-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+product	I-GENE
+is	O
+a	O
+member	O
+of	O
+a	O
+highly	O
+conserved	O
+family	O
+of	O
+proteins	O
+which	O
+are	O
+involved	O
+in	O
+post	O
+-	O
+replication	O
+mismatch	O
+repair	O
+.	O
+hMSH	B-GENE
+-	I-GENE
+2	I-GENE
+is	O
+homologous	O
+to	O
+Escherichia	O
+coli	O
+(	O
+E	O
+.	O
+coli	O
+)	O
+MutS	B-GENE
+and	O
+Sacchromyces	B-GENE
+cerevisiae	I-GENE
+MSH	I-GENE
+-	I-GENE
+1	I-GENE
+and	O
+MSH	B-GENE
+-	I-GENE
+2	I-GENE
+proteins	I-GENE
+,	O
+which	O
+recognise	O
+heteroduplex	O
+DNA	O
+at	O
+the	O
+sites	O
+of	O
+all	O
+single	O
+base	O
+mismatches	O
+and	O
+deletions	O
+or	O
+insertions	O
+up	O
+to	O
+4	O
+base	O
+pairs	O
+.	O
+hMSH	B-GENE
+-	I-GENE
+2	I-GENE
+is	O
+one	O
+of	O
+the	O
+hereditary	B-GENE
+non	I-GENE
+-	I-GENE
+polyposis	I-GENE
+colorectal	I-GENE
+cancer	I-GENE
+(	I-GENE
+HNPCC	I-GENE
+)	I-GENE
+tumor	I-GENE
+suppressor	I-GENE
+genes	I-GENE
+,	O
+and	O
+maps	O
+to	O
+human	O
+chromosome	O
+2p16	O
+.	O
+
+We	O
+have	O
+recently	O
+shown	O
+that	O
+the	O
+tissue	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+RAR	B-GENE
+beta	I-GENE
+2	I-GENE
+gene	I-GENE
+in	I-GENE
+mouse	I-GENE
+embryos	I-GENE
+is	O
+regulated	O
+at	O
+the	O
+translational	O
+level	O
+by	O
+short	O
+upstream	O
+open	O
+reading	O
+frames	O
+(	O
+uORFs	O
+)	O
+In	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+(	O
+Zimmer	O
+,	O
+A	O
+.	O
+,	O
+A	O
+.	O
+M	O
+.	O
+
+We	O
+have	O
+previously	O
+isolated	O
+a	O
+cDNA	O
+for	O
+a	O
+transcription	O
+factor	O
+referred	O
+to	O
+as	O
+Zfhep	B-GENE
+(	O
+zinc	B-GENE
+finger	I-GENE
+homeodomain	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+)	O
+containing	O
+two	O
+separate	O
+zinc	O
+finger	O
+domains	O
+,	O
+ZD1	B-GENE
+and	O
+ZD2	B-GENE
+,	O
+each	O
+of	O
+which	O
+binds	O
+DNA	O
+,	O
+and	O
+a	O
+homeodomain	O
+.	O
+
+Increased	O
+PTHRP	B-GENE
+production	O
+by	O
+a	O
+tyrosine	B-GENE
+kinase	I-GENE
+oncogene	I-GENE
+,	O
+Tpr	B-GENE
+-	I-GENE
+Met	I-GENE
+:	O
+role	O
+of	O
+the	O
+Ras	B-GENE
+signaling	O
+pathway	O
+.	O
+
+Subsequent	O
+to	O
+their	O
+secretion	O
+,	O
+the	O
+IGF	B-GENE
+-	I-GENE
+II	I-GENE
+in	O
+xz97	O
+and	O
+G11	O
+cells	O
+accumulated	O
+in	O
+the	O
+conditioned	O
+medium	O
+mostly	O
+as	O
+two	O
+partially	O
+processed	O
+species	O
+with	O
+appMr	O
+,	O
+of	O
+17K	O
+and	O
+14K	O
+,	O
+respectively	O
+.	O
+
+Paradoxically	O
+,	O
+coexpression	O
+of	O
+the	O
+transcriptionally	O
+inactive	O
+,	O
+amino	O
+-	O
+terminally	O
+deleted	O
+IDX	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+proteins	I-GENE
+,	O
+either	O
+with	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+IDX	I-GENE
+-	I-GENE
+1	I-GENE
+or	O
+with	O
+themselves	O
+,	O
+results	O
+in	O
+a	O
+marked	O
+enhancement	O
+of	O
+transactivation	O
+of	O
+the	O
+transcriptional	O
+TAAT	B-GENE
+-	I-GENE
+1	I-GENE
+element	I-GENE
+reporter	I-GENE
+.	O
+
+All	O
+patients	O
+had	O
+abnormal	O
+von	B-GENE
+Willebrand	I-GENE
+factor	I-GENE
+(	O
+vWF	B-GENE
+)	O
+fragmentation	O
+as	O
+reflected	O
+by	O
+decreased	O
+high	O
+molecular	O
+weight	O
+and	O
+increased	O
+low	O
+molecular	O
+weight	O
+vWF	B-GENE
+multimers	I-GENE
+in	O
+the	O
+circulation	O
+.	O
+
+In	O
+an	O
+attempt	O
+to	O
+investigate	O
+whether	O
+the	O
+intergenic	O
+region	O
+between	O
+the	O
+oleosin	B-GENE
+and	O
+a	O
+second	O
+open	O
+reading	O
+frame	O
+(	O
+ORFII	O
+)	O
+in	O
+Brassica	O
+napus	O
+(	O
+L	O
+.	O
+)	O
+is	O
+a	O
+divergent	O
+promoter	O
+,	O
+and	O
+also	O
+to	O
+characterize	O
+the	O
+ORFII	B-GENE
+,	O
+cDNA	B-GENE
+clones	I-GENE
+homologous	I-GENE
+to	I-GENE
+ORFII	I-GENE
+were	O
+isolated	O
+from	O
+a	O
+leaf	O
+cDNA	O
+library	O
+.	O
+
+The	O
+ORFII	B-GENE
+gene	I-GENE
+product	I-GENE
+is	O
+targeted	O
+to	O
+the	O
+chloroplast	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+previous	O
+data	O
+indicating	O
+the	O
+presence	O
+of	O
+PMSR	B-GENE
+activity	O
+in	O
+the	O
+chloroplast	O
+.	O
+
+Characterization	O
+of	O
+LRP	B-GENE
+,	O
+a	O
+leucine	B-GENE
+-	I-GENE
+rich	I-GENE
+repeat	I-GENE
+(	I-GENE
+LRR	I-GENE
+)	I-GENE
+protein	I-GENE
+from	I-GENE
+tomato	I-GENE
+plants	I-GENE
+that	O
+is	O
+processed	O
+during	O
+pathogenesis	O
+.	O
+
+To	O
+test	O
+whether	O
+Sp1	B-GENE
+and	O
+zif268	B-GENE
+/	O
+egr	B-GENE
+-	I-GENE
+1	I-GENE
+interact	O
+with	O
+this	O
+motif	O
+,	O
+gel	O
+retardation	O
+assays	O
+were	O
+performed	O
+.	O
+
+OBJECTIVES	O
+:	O
+The	O
+aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+analyze	O
+the	O
+clinical	O
+characteristics	O
+,	O
+treatment	O
+and	O
+outcome	O
+of	O
+310	O
+patients	O
+with	O
+hydatidiform	O
+mole	O
+.	O
+
+Stably	O
+transfected	O
+human	O
+kidney	O
+293	O
+cells	O
+expressing	O
+the	O
+wild	B-GENE
+type	I-GENE
+rat	I-GENE
+LH	I-GENE
+/	I-GENE
+CG	I-GENE
+receptor	I-GENE
+(	O
+rLHR	B-GENE
+)	O
+or	O
+receptors	O
+with	O
+C	O
+-	O
+terminal	O
+tails	O
+truncated	O
+at	O
+residues	O
+653	O
+,	O
+631	O
+,	O
+or	O
+628	O
+(	O
+designated	O
+rLHR	B-GENE
+-	I-GENE
+t653	I-GENE
+,	O
+rLHR	B-GENE
+-	I-GENE
+t631	I-GENE
+,	O
+and	O
+rLHR	B-GENE
+-	I-GENE
+t628	I-GENE
+)	O
+were	O
+used	O
+to	O
+probe	O
+the	O
+importance	O
+of	O
+this	O
+region	O
+on	O
+the	O
+regulation	O
+of	O
+hormonal	O
+responsiveness	O
+.	O
+
+Are	O
+low	O
+P300	O
+amplitudes	O
+a	O
+marker	O
+for	O
+schizophrenia	O
+.	O
+
+Sleep	O
+was	O
+determined	O
+again	O
+for	O
+an	O
+additional	O
+3	O
+days	O
+and	O
+6	O
+hours	O
+.	O
+
+The	O
+patients	O
+are	O
+two	O
+healthy	O
+adult	O
+males	O
+.	O
+
+Indoor	O
+concentrations	O
+were	O
+only	O
+weakly	O
+correlated	O
+with	O
+outdoor	O
+concentrations	O
+,	O
+however	O
+,	O
+and	O
+personal	O
+exposures	O
+were	O
+even	O
+more	O
+poorly	O
+correlated	O
+with	O
+outdoor	O
+concentrations	O
+.	O
+
+A	O
+neuropsychological	O
+test	O
+battery	O
+was	O
+used	O
+that	O
+contained	O
+the	O
+Wisconsin	O
+card	O
+sorting	O
+test	O
+,	O
+Street	O
+completion	O
+test	O
+,	O
+Stroop	O
+test	O
+,	O
+a	O
+dichotic	O
+memory	O
+listening	O
+test	O
+,	O
+and	O
+a	O
+facial	O
+recognition	O
+test	O
+.	O
+
+We	O
+present	O
+this	O
+case	O
+because	O
+of	O
+the	O
+rarity	O
+of	O
+left	O
+ventricular	O
+involvement	O
+associated	O
+with	O
+ARVD	O
+.	O
+
+In	O
+a	O
+randomized	O
+single	O
+-	O
+blind	O
+3	O
+x	O
+3	O
+Latin	O
+-	O
+square	O
+study	O
+with	O
+corrections	O
+for	O
+any	O
+carryover	O
+effects	O
+,	O
+27	O
+males	O
+and	O
+30	O
+females	O
+consumed	O
+supplements	O
+containing	O
+glucose	O
+or	O
+resistant	O
+starch	O
+(	O
+RS	O
+)	O
+from	O
+raw	O
+high	O
+-	O
+amylose	O
+cornstarch	O
+(	O
+RS2	O
+)	O
+or	O
+from	O
+retrograded	O
+high	O
+-	O
+amylose	O
+cornstarch	O
+(	O
+RS3	O
+)	O
+.	O
+
+The	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+mouse	B-GENE
+Met	I-GENE
+-	I-GENE
+ase	I-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+also	O
+shares	O
+considerable	O
+regions	O
+of	O
+identity	O
+with	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+rat	B-GENE
+Met	I-GENE
+-	I-GENE
+ase	I-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+[	O
+18F	O
+]	O
+FMISO	O
+TMRR	O
+is	O
+a	O
+simple	O
+and	O
+clinically	O
+useful	O
+index	O
+for	O
+detecting	O
+tumour	O
+hypoxia	O
+in	O
+NPC	O
+.	O
+
+Improved	O
+methods	O
+have	O
+been	O
+developed	O
+for	O
+maintaining	O
+and	O
+breeding	O
+the	O
+neotropical	O
+short	O
+-	O
+tailed	O
+fruit	O
+bat	O
+,	O
+Carollia	O
+perspicillata	O
+,	O
+in	O
+an	O
+easily	O
+-	O
+reproduced	O
+,	O
+laboratory	O
+setting	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+time	O
+to	O
+engraftment	O
+was	O
+significantly	O
+shorter	O
+in	O
+the	O
+amifostine	O
+arm	O
+in	O
+both	O
+cohorts	O
+.	O
+
+We	O
+conclude	O
+that	O
+CPET	O
+is	O
+a	O
+useful	O
+investigation	O
+in	O
+the	O
+management	O
+of	O
+patients	O
+with	O
+cardiopulmonary	O
+disease	O
+and	O
+complements	O
+the	O
+various	O
+other	O
+investigations	O
+offered	O
+by	O
+a	O
+pulmonary	O
+function	O
+laboratory	O
+.	O
+
+Using	O
+fluorescence	O
+in	O
+situ	O
+hybridization	O
+,	O
+we	O
+mapped	O
+the	O
+chromosome	O
+-	O
+17	O
+breakpoint	O
+in	O
+a	O
+patient	O
+with	O
+acampomelic	O
+CMPD	O
+and	O
+sex	O
+reversal	O
+,	O
+who	O
+carries	O
+a	O
+de	O
+novo	O
+constitutional	O
+t	O
+(	O
+12	O
+;	O
+17	O
+)	O
+translocation	O
+,	O
+between	O
+two	O
+known	O
+cosmid	O
+markers	O
+in	O
+the	O
+17q24	O
+-	O
+q25	O
+region	O
+.	O
+
+This	O
+is	O
+concluded	O
+from	O
+the	O
+isolation	O
+of	O
+cDNAs	O
+from	O
+spinach	O
+(	O
+Spinacia	O
+oleracea	O
+)	O
+and	O
+barley	O
+(	O
+Hordeum	O
+vulgare	O
+cv	O
+.	O
+
+The	O
+data	O
+presented	O
+in	O
+this	O
+work	O
+indicate	O
+that	O
+thi1	B-GENE
+may	O
+also	O
+be	O
+involved	O
+in	O
+DNA	O
+damage	O
+tolerance	O
+in	O
+plant	O
+cells	O
+.	O
+
+In	O
+the	O
+rat	B-GENE
+rnu	I-GENE
+allele	I-GENE
+described	O
+here	O
+,	O
+a	O
+nonsense	O
+mutation	O
+in	O
+exon	O
+8	O
+of	O
+the	O
+whn	B-GENE
+gene	I-GENE
+was	O
+identified	O
+.	O
+
+Control	O
+intact	O
+rats	O
+were	O
+age	O
+-	O
+matched	O
+to	O
+the	O
+different	O
+treated	O
+groups	O
+.	O
+
+DESIGN	O
+:	O
+A	O
+cross	O
+-	O
+sectional	O
+study	O
+.	O
+
+We	O
+have	O
+identified	O
+a	O
+strong	O
+Tas	B-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+,	O
+designated	O
+TRE	B-GENE
+(	O
+GP	B-GENE
+)	O
+,	O
+near	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+gag	B-GENE
+gene	I-GENE
+and	O
+preceding	O
+the	O
+pol	B-GENE
+gene	I-GENE
+of	O
+SFV	O
+-	O
+1	O
+.	O
+
+Although	O
+the	O
+binding	O
+of	O
+IE2	B-GENE
+86	I-GENE
+to	O
+nonphosphorylated	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+CREB	I-GENE
+or	O
+deltaCREB	B-GENE
+is	O
+minimal	O
+,	O
+IE2	B-GENE
+86	I-GENE
+does	O
+form	O
+complexes	O
+with	O
+p300	B-GENE
+and	O
+the	O
+CREB	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+CBP	B-GENE
+)	O
+,	O
+which	O
+in	O
+turn	O
+bind	O
+to	O
+CREB	B-GENE
+and	O
+can	O
+serve	O
+as	O
+adaptor	O
+proteins	O
+for	O
+CREB	B-GENE
+function	O
+.	O
+
+A	O
+transgenic	O
+complementation	O
+assay	O
+was	O
+used	O
+to	O
+test	O
+whether	O
+NIa	B-GENE
+supplied	O
+in	O
+trans	O
+could	O
+rescue	O
+amplification	O
+-	O
+defective	O
+viral	O
+genomes	O
+encoding	O
+altered	O
+NIa	B-GENE
+proteins	I-GENE
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+its	O
+bZIP	O
+structural	O
+homology	O
+,	O
+meq	B-GENE
+is	O
+perhaps	O
+the	O
+only	O
+member	O
+of	O
+the	O
+jun	B-GENE
+-	O
+fos	B-GENE
+gene	O
+family	O
+completely	O
+viral	O
+in	O
+origin	O
+.	O
+
+The	O
+rCBF	O
+and	O
+vasomotion	O
+were	O
+recorded	O
+by	O
+laser	O
+-	O
+doppler	O
+fluxmetry	O
+.	O
+
+Although	O
+basal	O
+vessels	O
+may	O
+constrict	O
+distal	O
+parenchymal	O
+vessels	O
+tend	O
+to	O
+dilate	O
+after	O
+SAH	O
+.	O
+
+The	O
+triple	O
+combination	O
+of	O
+nizatidine	O
+,	O
+clarithromycin	O
+,	O
+and	O
+bismuth	O
+subcitrate	O
+resulted	O
+in	O
+an	O
+ulcer	O
+healing	O
+rate	O
+of	O
+98	O
+%	O
+and	O
+an	O
+H	O
+.	O
+pylori	O
+eradication	O
+rate	O
+of	O
+90	O
+%	O
+.	O
+
+Several	O
+lines	O
+of	O
+evidence	O
+presented	O
+here	O
+suggest	O
+that	O
+PKC	B-GENE
+-	I-GENE
+zeta	I-GENE
+plays	O
+a	O
+role	O
+in	O
+alpha	B-GENE
+2	I-GENE
+integrin	I-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Plasma	O
+thrombomodulin	B-GENE
+:	O
+a	O
+marker	O
+for	O
+microvascular	O
+complications	O
+in	O
+diabetes	O
+mellitus	O
+.	O
+
+Update	O
+:	O
+diphtheria	O
+epidemic	O
+in	O
+the	O
+newly	O
+independent	O
+states	O
+of	O
+the	O
+former	O
+USSR	O
+,	O
+January	O
+1995	O
+-	O
+March	O
+1996	O
+.	O
+
+The	O
+characterization	O
+of	O
+the	O
+promoter	O
+region	O
+indicated	O
+that	O
+three	O
+distinct	O
+regulatory	O
+elements	O
+corresponding	O
+to	O
+an	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+site	I-GENE
+(	O
+or	O
+TRE	O
+)	O
+,	O
+a	O
+PRDII	B-GENE
+/	O
+kappaB	B-GENE
+domain	O
+,	O
+and	O
+a	O
+CAAT	O
+box	O
+are	O
+involved	O
+in	O
+the	O
+activation	O
+by	O
+pp60	B-GENE
+(	B-GENE
+v	I-GENE
+-	I-GENE
+)	I-GENE
+src	I-GENE
+.	O
+
+Serine	O
+528	O
+is	O
+phosphorylated	O
+in	O
+vivo	O
+in	O
+several	O
+cell	O
+lines	O
+,	O
+and	O
+substitution	O
+of	O
+serine	O
+528	O
+to	O
+alanine	O
+(	O
+S528A	O
+)	O
+resulted	O
+in	O
+an	O
+increased	O
+ability	O
+of	O
+Myb	B-GENE
+to	O
+transactivate	O
+a	O
+synthetic	O
+promoter	O
+containing	O
+five	O
+copies	O
+of	O
+the	O
+mim	B-GENE
+-	I-GENE
+1A	I-GENE
+Myb	B-GENE
+-	O
+responsive	O
+element	O
+and	O
+a	O
+minimal	O
+herpes	B-GENE
+tk	I-GENE
+promoter	I-GENE
+.	O
+
+The	O
+DNA	O
+binding	O
+and	O
+multimerization	O
+activities	O
+of	O
+c	B-GENE
+-	I-GENE
+Myb	I-GENE
+appear	O
+to	O
+be	O
+unaffected	O
+by	O
+the	O
+S528A	O
+substitution	O
+,	O
+suggesting	O
+that	O
+phosphorylation	O
+of	O
+serine	O
+528	O
+may	O
+mediate	O
+its	O
+effect	O
+on	O
+the	O
+transcription	O
+transactivating	O
+activity	O
+of	O
+c	B-GENE
+-	I-GENE
+Myb	I-GENE
+by	O
+regulating	O
+interactions	O
+with	O
+other	O
+proteins	O
+.	O
+
+The	O
+amount	O
+of	O
+these	O
+factors	O
+was	O
+reduced	O
+in	O
+GEO	O
+cells	O
+in	O
+which	O
+the	O
+u	B-GENE
+-	I-GENE
+PAR	I-GENE
+gene	I-GENE
+is	O
+only	O
+weakly	O
+transcriptionally	O
+activated	O
+.	O
+
+PIP2	O
+,	O
+when	O
+incorporated	O
+into	O
+phosphatidylcholine	O
+carrier	O
+vesicles	O
+,	O
+binds	O
+tightly	O
+to	O
+the	O
+guanine	O
+nucleotide	O
+-	O
+depleted	O
+form	O
+of	O
+Cdc42Hs	B-GENE
+and	O
+weakly	O
+to	O
+the	O
+GDP	O
+-	O
+bound	O
+form	O
+of	O
+the	O
+GTP	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+but	O
+does	O
+not	O
+bind	O
+to	O
+GTP	O
+-	O
+bound	O
+Cdc42Hs	B-GENE
+,	O
+similar	O
+to	O
+what	O
+was	O
+observed	O
+for	O
+the	O
+Dbl	B-GENE
+oncoprotein	I-GENE
+.	O
+
+Purified	O
+spleen	O
+GAP	B-GENE
+accelerated	O
+hydrolysis	O
+of	O
+GTP	O
+bound	O
+to	O
+recombinant	B-GENE
+ARF1	I-GENE
+,	O
+ARF3	B-GENE
+,	O
+ARF5	B-GENE
+,	O
+and	O
+ARF6	B-GENE
+;	O
+no	O
+effect	O
+of	O
+NH2	O
+-	O
+terminal	O
+myristoylation	O
+was	O
+observed	O
+.	O
+
+Biol	O
+.	O
+
+A	O
+novel	O
+phosphotyrosine	O
+-	O
+binding	O
+domain	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+transforming	O
+region	O
+of	O
+Cbl	B-GENE
+interacts	O
+directly	O
+and	O
+selectively	O
+with	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+in	O
+T	O
+cells	O
+.	O
+
+Cys	O
+-	O
+757	O
+within	O
+the	O
+(	O
+Fe4S4	O
+)	O
+-	O
+siroheme	O
+-	O
+binding	O
+domain	O
+was	O
+essential	O
+for	O
+native	O
+enzyme	O
+activity	O
+.	O
+
+Its	O
+transcription	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+induced	O
+40	O
+-	O
+50	O
+-	O
+fold	O
+in	O
+response	O
+to	O
+oxygen	O
+or	O
+heme	O
+deficiency	O
+,	O
+in	O
+part	O
+through	O
+relief	O
+of	O
+repression	O
+exerted	O
+by	O
+Rox1p	B-GENE
+and	O
+in	O
+part	O
+by	O
+activation	O
+mediated	O
+by	O
+an	O
+upstream	O
+activation	O
+sequence	O
+(	O
+UAS	O
+)	O
+.	O
+
+Altogether	O
+,	O
+our	O
+results	O
+indicate	O
+that	O
+the	O
+transcriptional	O
+activity	O
+of	O
+Cut	B-GENE
+proteins	I-GENE
+is	O
+modulated	O
+by	O
+PKC	B-GENE
+.	O
+
+Lck	B-GENE
+has	O
+been	O
+postulated	O
+to	O
+dimerize	O
+through	O
+the	O
+SH2	B-GENE
+and	O
+SH3	B-GENE
+domains	I-GENE
+.	O
+
+Furthermore	O
+,	O
+freezing	O
+in	O
+the	O
+presence	O
+of	O
+bovine	B-GENE
+lactalbumin	I-GENE
+resulted	O
+in	O
+a	O
+good	O
+maintenance	O
+of	O
+the	O
+cellular	O
+viability	O
+and	O
+of	O
+the	O
+CCCD	O
+heterogeneity	O
+in	O
+respect	O
+to	O
+fresh	O
+cells	O
+.	O
+
+Myelomatous	O
+pleural	O
+effusion	O
+as	O
+presentation	O
+form	O
+of	O
+multiple	O
+myeloma	O
+
+The	O
+presence	O
+of	O
+unidentified	O
+macroscopic	O
+or	O
+microscopic	O
+clusters	O
+of	O
+neoplastic	O
+cells	O
+,	O
+lying	O
+around	O
+,	O
+more	O
+or	O
+less	O
+close	O
+to	O
+,	O
+the	O
+line	O
+of	O
+insertion	O
+of	O
+lesion	O
+,	O
+could	O
+render	O
+any	O
+attempt	O
+to	O
+gain	O
+a	O
+"	O
+radical	O
+"	O
+excision	O
+useless	O
+.	O
+
+The	O
+partial	O
+categories	O
+of	O
+the	O
+SIP	O
+that	O
+were	O
+more	O
+affected	O
+were	O
+work	O
+,	O
+recreation	O
+and	O
+pastimes	O
+,	O
+home	O
+management	O
+,	O
+and	O
+sleep	O
+and	O
+rest	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+,	O
+using	O
+the	O
+Ltp4	B-GENE
+-	O
+specific	O
+probe	O
+,	O
+indicated	O
+that	O
+Xanthomonas	O
+campestris	O
+pv	O
+.	O
+translucens	O
+induced	O
+an	O
+increase	O
+over	O
+basal	O
+levels	O
+of	O
+Ltp4	B-GENE
+mRNA	I-GENE
+,	O
+while	O
+Pseudomonas	O
+syringae	O
+pv	O
+.	O
+japonica	O
+caused	O
+a	O
+decrease	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+use	O
+of	O
+zero	O
+-	O
+loss	O
+filtering	O
+in	O
+combination	O
+with	O
+exit	O
+wavefront	O
+reconstruction	O
+is	O
+considerably	O
+more	O
+effective	O
+at	O
+removing	O
+the	O
+effects	O
+of	O
+multiple	O
+elastic	O
+and	O
+inelastic	O
+scattering	O
+and	O
+microscope	O
+objective	O
+lens	O
+aberrations	O
+than	O
+either	O
+technique	O
+by	O
+itself	O
+.	O
+
+Transcripts	O
+for	O
+both	O
+ODV	B-GENE
+-	I-GENE
+E18	I-GENE
+and	O
+ODV	B-GENE
+-	I-GENE
+EC27	I-GENE
+initiate	O
+from	O
+conserved	O
+TAAG	O
+motifs	O
+,	O
+and	O
+transcripts	O
+are	O
+detected	O
+from	O
+16	O
+through	O
+72	O
+hr	O
+p	O
+.	O
+i	O
+.	O
+
+In	O
+order	O
+to	O
+determine	O
+which	O
+sequences	O
+in	O
+the	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+are	O
+crucial	O
+for	O
+activation	O
+by	O
+the	O
+ME26	B-GENE
+viral	I-GENE
+protein	I-GENE
+,	O
+we	O
+made	O
+deletions	O
+of	O
+the	O
+promoter	O
+,	O
+cloned	O
+them	O
+into	O
+a	O
+luciferase	B-GENE
+expression	O
+vector	O
+and	O
+tested	O
+their	O
+activity	O
+in	O
+mouse	O
+fibroblasts	O
+,	O
+which	O
+do	O
+not	O
+express	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+A	O
+3	O
+-	O
+yr	O
+retrospective	O
+review	O
+is	O
+effective	O
+and	O
+detects	O
+94	O
+%	O
+of	O
+the	O
+undercalls	O
+.	O
+
+Isolation	O
+and	O
+identification	O
+of	O
+genes	O
+activating	O
+UAS2	B-GENE
+-	I-GENE
+dependent	I-GENE
+ADH2	I-GENE
+expression	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+A	O
+64	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+confirmed	O
+AV	O
+nodal	O
+reentrant	O
+tachycardia	O
+underwent	O
+a	O
+successful	O
+"	O
+slow	O
+pathway	O
+"	O
+AV	O
+modification	O
+with	O
+a	O
+single	O
+radiofrequency	O
+application	O
+.	O
+
+Patients	O
+with	O
+low	O
+probability	O
+of	O
+having	O
+aluminum	O
+overload	O
+(	O
+serum	O
+iron	O
+levels	O
+<	O
+40	O
+micrograms	O
+/	O
+L	O
+and	O
+DAI	O
+<	O
+150	O
+micrograms	O
+/	O
+L	O
+)	O
+had	O
+significantly	O
+higher	O
+values	O
+of	O
+serum	O
+iron	O
+,	O
+iron	O
+transferrin	B-GENE
+saturation	O
+,	O
+and	O
+serum	B-GENE
+ferritin	I-GENE
+levels	O
+compared	O
+with	O
+those	O
+patients	O
+with	O
+a	O
+high	O
+probability	O
+of	O
+having	O
+aluminum	O
+overload	O
+(	O
+serum	O
+aluminum	O
+levels	O
+>	O
+40	O
+micrograms	O
+/	O
+L	O
+and	O
+DAI	O
+>	O
+150	O
+micrograms	O
+/	O
+L	O
+)	O
+.	O
+
+Although	O
+the	O
+RAD23	B-GENE
+equivalents	O
+are	O
+well	O
+conserved	O
+during	O
+evolution	O
+,	O
+the	O
+mammalian	O
+genes	O
+did	O
+not	O
+express	O
+the	O
+UV	O
+-	O
+inducible	O
+phenotype	O
+of	O
+their	O
+yeast	O
+counterpart	O
+.	O
+
+Ha	B-GENE
+-	I-GENE
+RasV12	I-GENE
+and	O
+activated	O
+proteins	O
+in	O
+both	O
+the	O
+extra	B-GENE
+-	I-GENE
+cellular	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+(	O
+ERK	B-GENE
+)	O
+and	O
+the	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+SAPK	B-GENE
+)	O
+or	O
+Jun	B-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+(	O
+JNK	B-GENE
+)	O
+cascades	O
+independently	O
+stimulated	O
+PEA3	B-GENE
+-	O
+mediated	O
+gene	O
+expression	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+reverse	O
+transcribed	O
+,	O
+amplified	O
+cDNA	O
+generated	O
+from	O
+total	O
+RNA	O
+isolated	O
+from	O
+transfected	O
+cells	O
+demonstrated	O
+the	O
+presence	O
+of	O
+abnormally	O
+spliced	O
+products	O
+containing	O
+13	O
+and	O
+78	O
+additional	O
+bases	O
+as	O
+well	O
+as	O
+the	O
+accumulation	O
+of	O
+unspliced	O
+mRNA	O
+.	O
+
+A	O
+1	O
+.	O
+5	O
+-	O
+kb	O
+HindIII	B-GENE
+genomic	O
+fragment	O
+carrying	O
+the	O
+vspA	B-GENE
+gene	O
+from	O
+M	O
+.	O
+bovis	O
+PG45	O
+was	O
+cloned	O
+and	O
+sequenced	O
+.	O
+
+Carbon	O
+catabolite	O
+repression	O
+of	O
+the	O
+gnt	B-GENE
+operon	I-GENE
+of	I-GENE
+Bacillus	I-GENE
+subtilis	I-GENE
+is	O
+mediated	O
+by	O
+the	O
+catabolite	O
+control	O
+protein	O
+CcpA	B-GENE
+and	O
+by	O
+HPr	B-GENE
+,	O
+a	O
+phosphocarrier	O
+protein	O
+of	O
+the	O
+phosphotransferase	O
+system	O
+.	O
+
+Melatonin	O
+and	O
+seasonality	O
+:	O
+filling	O
+the	O
+gap	O
+.	O
+
+A	O
+subsequent	O
+screen	O
+for	O
+the	O
+loss	O
+of	O
+the	O
+positively	O
+selectable	O
+target	O
+locus	O
+marker	O
+detects	O
+the	O
+desired	O
+replacement	O
+at	O
+modest	O
+frequency	O
+(	O
+>	O
+2	O
+%	O
+)	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+another	O
+cellular	O
+protein	O
+linked	O
+to	O
+BCR	B-GENE
+/	O
+ABL	B-GENE
+through	O
+the	O
+CRKL	B-GENE
+-	O
+SH2	B-GENE
+domain	O
+is	O
+p130	B-GENE
+(	O
+CAS	B-GENE
+)	O
+.	O
+p130	B-GENE
+(	O
+CAS	B-GENE
+)	O
+was	O
+found	O
+to	O
+be	O
+tyrosine	O
+phosphorylated	O
+and	O
+associated	O
+with	O
+CRKL	B-GENE
+in	O
+BCR	B-GENE
+/	O
+ABL	B-GENE
+expressing	O
+cell	O
+lines	O
+and	O
+in	O
+samples	O
+obtained	O
+from	O
+CML	O
+and	O
+ALL	O
+patients	O
+,	O
+but	O
+not	O
+in	O
+samples	O
+from	O
+controls	O
+.	O
+
+The	O
+effects	O
+of	O
+procedural	O
+variations	O
+on	O
+lateralized	O
+Stroop	O
+effects	O
+.	O
+
+In	O
+a	O
+third	O
+experiment	O
+,	O
+a	O
+Chessmaster	O
+gradually	O
+increases	O
+the	O
+number	O
+of	O
+boards	O
+he	O
+can	O
+reproduce	O
+with	O
+higher	O
+than	O
+70	O
+%	O
+average	O
+accuracy	O
+to	O
+nine	O
+,	O
+replacing	O
+as	O
+many	O
+as	O
+160	O
+pieces	O
+correctly	O
+.	O
+
+PCNA	B-GENE
+mRNA	I-GENE
+has	O
+a	O
+3	O
+'	O
+UTR	O
+antisense	O
+to	O
+yellow	O
+crescent	O
+RNA	O
+and	O
+is	O
+localized	O
+in	O
+ascidian	O
+eggs	O
+and	O
+embryos	O
+.	O
+
+A	O
+1	O
+.	O
+8	O
+-	O
+kb	O
+cDNA	O
+clone	O
+(	O
+designed	O
+hKID	B-GENE
+,	O
+gene	B-GENE
+symbol	I-GENE
+AQP2L	I-GENE
+)	O
+with	O
+homology	O
+to	O
+the	O
+aquaporins	B-GENE
+was	O
+isolated	O
+from	O
+a	O
+human	O
+kidney	O
+cDNA	O
+library	O
+.	O
+
+PCR	O
+/	O
+Southern	O
+blot	O
+analysis	O
+of	O
+human	O
+kidney	O
+cDNA	O
+using	O
+primers	O
+flanking	O
+the	O
+hKID	B-GENE
+coding	I-GENE
+sequence	I-GENE
+revealed	O
+expression	O
+of	O
+a	O
+full	O
+-	O
+length	O
+mRNA	O
+and	O
+short	O
+transcripts	O
+with	O
+partial	O
+exon	O
+1	O
+and	O
+partial	O
+exon	O
+4	O
+deletions	O
+.	O
+
+The	O
+high	O
+sequence	O
+homology	O
+,	O
+similar	O
+genomic	O
+structure	O
+,	O
+and	O
+identical	O
+chromosomal	O
+loci	O
+of	O
+hKID	B-GENE
+,	O
+MIP	B-GENE
+,	O
+and	O
+AQP	B-GENE
+-	I-GENE
+2	I-GENE
+suggest	O
+a	O
+MIP	B-GENE
+family	I-GENE
+gene	I-GENE
+cluster	I-GENE
+at	O
+chromosome	O
+locus	O
+12q13	O
+.	O
+
+The	O
+third	O
+ORF	O
+generates	O
+a	O
+transcript	O
+of	O
+1	O
+.	O
+6	O
+kb	O
+and	O
+encodes	O
+a	O
+protein	O
+of	O
+382	O
+residues	O
+including	O
+a	O
+perfect	O
+match	O
+to	O
+the	O
+consensus	O
+sequence	O
+of	O
+a	O
+C2H2	O
+zinc	O
+finger	O
+domain	O
+;	O
+it	O
+shares	O
+a	O
+strong	O
+homology	O
+with	O
+yeast	B-GENE
+Mig1p	I-GENE
+and	O
+Cre	B-GENE
+-	I-GENE
+A	I-GENE
+from	I-GENE
+Aspergillus	I-GENE
+,	I-GENE
+Emericella	I-GENE
+and	I-GENE
+E	I-GENE
+.	I-GENE
+coli	I-GENE
+.	O
+
+Adding	O
+phytase	B-GENE
+and	O
+nP	O
+improved	O
+the	O
+orderliness	O
+of	O
+development	O
+,	O
+mineralization	O
+and	O
+arrangement	O
+of	O
+cartilage	O
+and	O
+bone	O
+cells	O
+,	O
+and	O
+alleviated	O
+the	O
+effects	O
+of	O
+P	O
+deficiency	O
+on	O
+the	O
+histological	O
+and	O
+gross	O
+structure	O
+of	O
+the	O
+tibias	O
+.	O
+
+The	O
+importance	O
+of	O
+temporal	O
+factors	O
+on	O
+the	O
+presence	O
+and	O
+severity	O
+of	O
+ethanol	O
+withdrawal	O
+signs	O
+in	O
+the	O
+rat	O
+was	O
+quantified	O
+using	O
+rating	O
+scale	O
+,	O
+tremor	O
+,	O
+and	O
+acoustic	O
+startle	O
+paradigms	O
+.	O
+
+Data	O
+supported	O
+the	O
+brevity	O
+of	O
+the	O
+WISC	O
+-	O
+III	O
+short	O
+form	O
+and	O
+the	O
+criterion	O
+-	O
+related	O
+validity	O
+of	O
+both	O
+the	O
+K	O
+-	O
+FAST	O
+and	O
+and	O
+Kaufman	O
+Short	O
+Neuropsychological	O
+Assessment	O
+Procedure	O
+(	O
+K	O
+-	O
+SNAP	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+multidomained	O
+ROK	B-GENE
+alpha	I-GENE
+appears	O
+to	O
+be	O
+involved	O
+in	O
+reorganization	O
+of	O
+the	O
+cytoskeleton	O
+,	O
+with	O
+the	O
+N	O
+and	O
+C	O
+termini	O
+acting	O
+as	O
+positive	O
+and	O
+negative	O
+regulators	O
+,	O
+respectively	O
+,	O
+of	O
+the	O
+kinase	O
+domain	O
+whose	O
+activity	O
+is	O
+crucial	O
+for	O
+formation	O
+of	O
+stress	O
+fibers	O
+and	O
+focal	O
+adhesion	O
+complexes	O
+.	O
+
+These	O
+findings	O
+and	O
+the	O
+differential	O
+tissue	O
+distribution	O
+of	O
+p54	B-GENE
+suggest	O
+that	O
+this	O
+novel	O
+SR	B-GENE
+protein	I-GENE
+may	O
+participate	O
+in	O
+regulation	O
+of	O
+alternative	O
+splicing	O
+in	O
+a	O
+tissue	O
+-	O
+and	O
+substrate	O
+-	O
+dependent	O
+manner	O
+.	O
+
+The	O
+elevation	O
+of	O
+cyclic	O
+AMP	O
+(	O
+cAMP	O
+)	O
+levels	O
+in	O
+the	O
+cell	O
+downregulates	O
+the	O
+activity	O
+of	O
+the	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+kinase	I-GENE
+.	O
+
+An	O
+interaction	O
+screen	O
+with	O
+the	O
+repression	O
+domain	O
+of	O
+the	O
+orphan	B-GENE
+receptor	I-GENE
+RevErb	I-GENE
+identified	O
+N	B-GENE
+-	I-GENE
+CoR	I-GENE
+,	O
+the	O
+corepressor	O
+for	O
+thyroid	B-GENE
+hormone	I-GENE
+receptor	I-GENE
+(	O
+TR	B-GENE
+)	O
+and	O
+retinoic	B-GENE
+acid	I-GENE
+receptor	I-GENE
+(	O
+RAR	B-GENE
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+inhibition	O
+of	O
+Jun	B-GENE
+kinase	I-GENE
+activation	O
+was	O
+sufficient	O
+to	O
+inhibit	O
+Ras	B-GENE
+transformation	O
+even	O
+in	O
+the	O
+presence	O
+of	O
+activated	O
+Erk	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+Our	O
+analysis	O
+suggests	O
+that	O
+Upf1p	B-GENE
+is	O
+a	O
+multifunctional	O
+protein	O
+with	O
+separable	O
+activities	O
+that	O
+can	O
+affect	O
+mRNA	O
+turnover	O
+and	O
+nonsense	O
+suppression	O
+.	O
+
+Identification	O
+of	O
+Ste4	B-GENE
+as	O
+a	O
+potential	O
+regulator	O
+of	O
+Byr2	B-GENE
+in	O
+the	O
+sexual	O
+response	O
+pathway	O
+of	O
+Schizosaccharomyces	O
+pombe	O
+.	O
+
+Two	O
+closely	O
+related	O
+variants	O
+of	O
+Stat5	B-GENE
+,	O
+Stat5a	B-GENE
+and	O
+Stat5b	B-GENE
+,	O
+are	O
+encoded	O
+by	O
+distinct	O
+genes	O
+.	O
+
+Mutations	O
+in	O
+three	O
+loci	O
+(	O
+SIC1	B-GENE
+,	O
+SWI5	B-GENE
+,	O
+and	O
+RIC3	B-GENE
+)	O
+were	O
+identified	O
+.	O
+
+The	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+functions	O
+downstream	O
+of	O
+Rats	B-GENE
+in	O
+a	O
+signal	O
+transduction	O
+cascade	O
+which	O
+transmits	O
+mitogenic	O
+stimuli	O
+from	O
+the	O
+plasma	O
+membrane	O
+to	O
+the	O
+nucleus	O
+.	O
+
+In	O
+transient	O
+cotransfections	O
+E1A	B-GENE
+could	O
+induce	O
+the	O
+activity	O
+of	O
+the	O
+p53	B-GENE
+promoter	I-GENE
+to	O
+a	O
+high	O
+level	O
+;	O
+12S	B-GENE
+E1A	I-GENE
+was	O
+threefold	O
+as	O
+efficient	O
+as	O
+13S	B-GENE
+E1A	I-GENE
+in	O
+this	O
+activity	O
+,	O
+and	O
+YY1	B-GENE
+bound	O
+to	O
+the	O
+composite	O
+element	O
+was	O
+shown	O
+to	O
+mediate	O
+55	O
+%	O
+of	O
+this	O
+induction	O
+.	O
+
+The	O
+retinoid	B-GENE
+Z	I-GENE
+receptor	I-GENE
+beta	I-GENE
+(	O
+RZR	B-GENE
+beta	I-GENE
+)	O
+,	O
+an	O
+orphan	O
+receptor	O
+,	O
+is	O
+a	O
+member	O
+of	O
+the	O
+retinoic	B-GENE
+acid	I-GENE
+receptor	I-GENE
+(	O
+RAR	B-GENE
+)	O
+/	O
+thyroid	B-GENE
+hormone	I-GENE
+receptor	I-GENE
+(	O
+TR	B-GENE
+)	O
+subfamily	O
+of	O
+nuclear	O
+receptors	O
+.	O
+
+DNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+DNA	B-GENE
+-	I-GENE
+PK	I-GENE
+)	O
+consists	O
+of	O
+a	O
+heterodimeric	O
+protein	O
+(	O
+Ku	B-GENE
+)	O
+and	O
+a	O
+large	O
+catalytic	O
+subunit	O
+(	O
+DNA	B-GENE
+-	I-GENE
+PKcs	I-GENE
+)	O
+.	O
+
+Sequencing	O
+of	O
+the	O
+16p	O
+11	O
+.	O
+1	O
+/	O
+Xq28	O
+duplication	O
+breakpoints	O
+has	O
+revealed	O
+the	O
+presence	O
+of	O
+repetitive	O
+immunoglobulin	B-GENE
+-	I-GENE
+like	I-GENE
+CAGGG	I-GENE
+pentamer	I-GENE
+sequences	I-GENE
+at	O
+or	O
+near	O
+the	O
+paralogy	O
+boundaries	O
+.	O
+
+However	O
+,	O
+in	O
+a	O
+multivariate	O
+analysis	O
+considering	O
+age	O
+,	O
+gender	O
+,	O
+and	O
+a	O
+previous	O
+history	O
+of	O
+cardiovascular	O
+diseases	O
+,	O
+female	O
+gender	O
+was	O
+not	O
+independently	O
+associated	O
+with	O
+death	O
+.	O
+
+Moreover	O
+,	O
+following	O
+a	O
+single	O
+intravenous	O
+injection	O
+of	O
+the	O
+bicistronic	O
+vector	O
+complexed	O
+to	O
+cationic	O
+liposomes	O
+into	O
+recipient	O
+mice	O
+,	O
+delivery	O
+of	O
+MDR1	B-GENE
+and	O
+GC	B-GENE
+cDNAs	I-GENE
+was	O
+achieved	O
+in	O
+all	O
+the	O
+organs	O
+we	O
+tested	O
+.	O
+
+The	O
+limits	O
+of	O
+agreement	O
+between	O
+DBS	O
+and	O
+TOF	O
+responses	O
+were	O
+so	O
+wide	O
+that	O
+they	O
+cannot	O
+be	O
+used	O
+interchangeably	O
+.	O
+
+The	O
+harpin	B-GENE
+-	O
+encoding	O
+hrpZ	B-GENE
+gene	I-GENE
+is	O
+located	O
+in	O
+an	O
+operon	O
+that	O
+also	O
+encodes	O
+Hrp	B-GENE
+secretion	I-GENE
+pathway	I-GENE
+components	I-GENE
+and	O
+is	O
+part	O
+of	O
+the	O
+functional	O
+cluster	O
+of	O
+hrp	B-GENE
+genes	I-GENE
+carried	O
+on	O
+cosmid	O
+pHIR11	O
+that	O
+enables	O
+saprophytic	O
+bacteria	O
+like	O
+Escherichia	O
+coli	O
+and	O
+Pseudomonas	O
+fluorescens	O
+to	O
+elicit	O
+the	O
+HR	O
+in	O
+tobacco	O
+leaves	O
+.	O
+
+Despite	O
+the	O
+presence	O
+of	O
+one	O
+additional	O
+ribonucleotide	B-GENE
+reductase	I-GENE
+,	O
+the	O
+nrdAB	B-GENE
+-	I-GENE
+encoded	I-GENE
+enzyme	I-GENE
+is	O
+essential	O
+to	O
+the	O
+aerobic	O
+growth	O
+of	O
+the	O
+cell	O
+because	O
+nrdAB	B-GENE
+-	I-GENE
+defective	I-GENE
+mutants	I-GENE
+of	O
+both	O
+species	O
+are	O
+not	O
+viable	O
+in	O
+the	O
+presence	O
+of	O
+oxygen	O
+.	O
+
+Altogether	O
+,	O
+the	O
+results	O
+demonstrate	O
+that	O
+the	O
+two	O
+isoforms	O
+elicit	O
+similar	O
+responses	O
+in	O
+vivo	O
+despite	O
+differences	O
+in	O
+their	O
+regulation	O
+.	O
+
+Motivational	O
+factors	O
+focusing	O
+on	O
+attitudes	O
+,	O
+perceived	O
+susceptibility	O
+to	O
+pregnancy	O
+,	O
+and	O
+normative	O
+factors	O
+were	O
+also	O
+relevant	O
+.	O
+
+High	O
+-	O
+resolution	O
+structure	O
+of	O
+the	O
+diphtheria	B-GENE
+toxin	I-GENE
+repressor	I-GENE
+complexed	O
+with	O
+cobalt	O
+and	O
+manganese	O
+reveals	O
+an	O
+SH3	B-GENE
+-	I-GENE
+like	I-GENE
+third	O
+domain	O
+and	O
+suggests	O
+a	O
+possible	O
+role	O
+of	O
+phosphate	O
+as	O
+co	O
+-	O
+corepressor	O
+.	O
+
+Titration	O
+of	O
+the	O
+human	O
+and	O
+porcine	O
+proteins	O
+with	O
+2	O
+-	O
+nitro	O
+-	O
+5	O
+-	O
+thiosulfabenzoate	O
+indicates	O
+that	O
+membrane	B-GENE
+dipeptidase	I-GENE
+additionally	O
+possesses	O
+two	O
+intrachain	O
+disulfide	O
+bonds	O
+.	O
+
+FEV1	O
+did	O
+not	O
+fall	O
+significantly	O
+in	O
+patients	O
+without	O
+acute	O
+or	O
+chronic	O
+GVHD	O
+and	O
+recovered	O
+earlier	O
+than	O
+in	O
+patients	O
+without	O
+posttransplant	O
+pulmonary	O
+infection	O
+.	O
+
+Administration	O
+of	O
+adrenaline	O
+resulted	O
+in	O
+a	O
+large	O
+overestimation	O
+of	O
+the	O
+SaO2	O
+in	O
+6	O
+of	O
+the	O
+7	O
+measurements	O
+.	O
+
+Therapy	O
+with	O
+dietary	O
+modification	O
+and	O
+triglyceride	O
+lowering	O
+drugs	O
+resulted	O
+in	O
+resolution	O
+of	O
+symptoms	O
+and	O
+parotid	O
+swelling	O
+in	O
+one	O
+patient	O
+.	O
+
+Chernoff	O
+,	O
+submitted	O
+for	O
+publication	O
+)	O
+.	O
+
+We	O
+have	O
+cloned	O
+a	O
+novel	O
+protein	O
+kinase	O
+,	O
+termed	O
+hematopoietic	B-GENE
+progenitor	I-GENE
+kinase	I-GENE
+1	I-GENE
+(	O
+HPK1	B-GENE
+)	O
+,	O
+that	O
+is	O
+expressed	O
+predominantly	O
+in	O
+hematopoietic	O
+cells	O
+,	O
+including	O
+early	O
+progenitor	O
+cells	O
+.	O
+
+Human	O
+ESP1	B-GENE
+/	O
+CRP2	B-GENE
+protein	O
+has	O
+two	O
+LIM	B-GENE
+domains	O
+,	O
+and	O
+each	O
+shares	O
+35	O
+.	O
+1	O
+%	O
+and	O
+77	O
+or	O
+79	O
+%	O
+identical	O
+residues	O
+with	O
+human	B-GENE
+cysteine	I-GENE
+-	I-GENE
+rich	I-GENE
+protein	I-GENE
+(	O
+CRP	B-GENE
+)	O
+and	O
+rat	B-GENE
+CRIP	I-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+fragments	O
+are	O
+separated	O
+and	O
+directly	O
+sized	O
+by	O
+agarose	O
+gel	O
+electrophoresis	O
+.	O
+
+Linkage	O
+studies	O
+have	O
+shown	O
+locus	O
+heterogeneity	O
+with	O
+one	O
+TSC	B-GENE
+gene	I-GENE
+mapped	O
+to	O
+chromosome	O
+9q34	O
+and	O
+a	O
+second	O
+to	O
+16p13	O
+.	O
+3	O
+.	O
+
+The	O
+cytogenetic	O
+expression	O
+of	O
+the	O
+folate	O
+sensitive	O
+fragile	O
+site	O
+,	O
+FRAXE	B-GENE
+,	O
+is	O
+due	O
+to	O
+the	O
+expansion	O
+of	O
+a	O
+GCC	O
+repeat	O
+in	O
+proximal	O
+Xq28	O
+of	O
+the	O
+human	O
+X	O
+chromosome	O
+and	O
+is	O
+associated	O
+with	O
+a	O
+mild	O
+form	O
+of	O
+mental	O
+handicap	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+of	O
+a	O
+3213	O
+bp	O
+BamHI	B-GENE
+-	O
+ClaI	B-GENE
+fragment	O
+revealed	O
+that	O
+three	O
+open	O
+reading	O
+frames	O
+(	O
+ORFs	O
+)	O
+were	O
+encoded	O
+in	O
+the	O
+same	O
+orientation	O
+.	O
+
+The	O
+initial	O
+inpatient	O
+experience	O
+for	O
+individuals	O
+with	O
+HIV	O
+-	O
+related	O
+TB	O
+may	O
+be	O
+pivotal	O
+to	O
+the	O
+acceptance	O
+of	O
+and	O
+participation	O
+in	O
+ongoing	O
+TB	O
+care	O
+.	O
+
+This	O
+element	O
+,	O
+termed	O
+CREsp	O
+-	O
+a	O
+(	O
+TGACCTCA	O
+)	O
+,	O
+differs	O
+by	O
+one	O
+nucleotide	O
+from	O
+a	O
+palindromic	O
+CRE	O
+(	O
+CREpal	O
+,	O
+TGACGTCA	O
+)	O
+,	O
+which	O
+is	O
+known	O
+to	O
+bind	O
+CREB	B-GENE
+as	O
+a	O
+homodimer	O
+.	O
+
+Analysis	O
+of	O
+human	O
+genomic	O
+DNA	O
+reveals	O
+an	O
+intronless	O
+sequence	O
+with	O
+strong	O
+homology	O
+to	O
+human	B-GENE
+G	I-GENE
+alpha	I-GENE
+q	I-GENE
+cDNA	I-GENE
+.	O
+
+The	O
+complete	O
+exon	O
+-	O
+intron	O
+structure	O
+of	O
+the	O
+156	B-GENE
+-	I-GENE
+kb	I-GENE
+human	I-GENE
+gene	I-GENE
+NFKB1	I-GENE
+,	O
+which	O
+encodes	O
+the	O
+p105	B-GENE
+and	O
+p50	B-GENE
+proteins	I-GENE
+of	O
+transcription	O
+factors	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+and	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+-	I-GENE
+gamma	I-GENE
+:	O
+implications	O
+for	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+-	O
+mediated	O
+signal	O
+transduction	O
+.	O
+
+An	O
+inverted	O
+Alu	B-GENE
+repeat	O
+element	O
+,	O
+flanked	O
+by	O
+nonamer	O
+direct	O
+repeats	O
+,	O
+was	O
+identified	O
+within	O
+the	O
+region	O
+-	O
+913	O
+/	O
+-	O
+620	O
+,	O
+relative	O
+to	O
+the	O
+cap	O
+site	O
+.	O
+
+Comparison	O
+of	O
+the	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+RPO1	B-GENE
+polypeptides	I-GENE
+of	I-GENE
+IIV6	I-GENE
+,	I-GENE
+LCDV	I-GENE
+,	I-GENE
+and	I-GENE
+MCV	I-GENE
+-	I-GENE
+1	I-GENE
+with	O
+the	O
+corresponding	O
+prokaryotic	O
+,	O
+eukaryotic	O
+,	O
+and	O
+viral	O
+proteins	O
+revealed	O
+differences	O
+in	O
+amino	O
+acid	O
+similarity	O
+and	O
+phylogenetic	O
+relationships	O
+.	O
+
+The	O
+RPO1	B-GENE
+of	O
+LCDV	O
+shows	O
+the	O
+highest	O
+similarity	O
+to	O
+the	O
+RPO1	B-GENE
+of	O
+IIV6	O
+and	O
+significant	O
+lower	O
+similarity	O
+to	O
+the	O
+eukaryotic	B-GENE
+polymerases	I-GENE
+II	I-GENE
+and	I-GENE
+III	I-GENE
+as	O
+well	O
+as	O
+to	O
+the	O
+archaebacteral	O
+subunit	O
+.	O
+
+The	O
+use	O
+of	O
+primary	O
+GE	O
+cells	O
+thus	O
+provides	O
+a	O
+convenient	O
+in	O
+vitro	O
+system	O
+for	O
+further	O
+study	O
+of	O
+the	O
+endocrine	O
+,	O
+paracrine	O
+,	O
+and	O
+autocrine	O
+factors	O
+regulating	O
+endometrial	O
+gene	O
+expression	O
+during	O
+pregnancy	O
+.	O
+
+We	O
+performed	O
+dipole	O
+estimation	O
+of	O
+spikes	O
+and	O
+SEP	O
+components	O
+in	O
+identical	O
+patients	O
+.	O
+
+Proximal	O
+CBD	O
+was	O
+inversely	O
+correlated	O
+with	O
+bone	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+71	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+and	O
+intact	O
+PTH	B-GENE
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+59	O
+,	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+comparison	O
+of	O
+the	O
+hCHLR	B-GENE
+gene	I-GENE
+sequences	I-GENE
+with	O
+available	O
+databases	O
+indicates	O
+that	O
+a	O
+large	O
+portion	O
+of	O
+these	O
+genes	O
+,	O
+including	O
+exons	O
+encoding	O
+two	O
+functional	O
+domains	O
+of	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+region	O
+of	O
+these	O
+proteins	O
+,	O
+has	O
+been	O
+duplicated	O
+as	O
+part	O
+of	O
+a	O
+larger	O
+human	O
+telomeric	O
+repeat	O
+sequence	O
+found	O
+on	O
+many	O
+human	O
+chromosomes	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+the	O
+LIM	B-GENE
+domain	I-GENE
+homeobox	B-GENE
+protein	I-GENE
+isl	B-GENE
+-	I-GENE
+1	I-GENE
+activates	O
+the	O
+rat	B-GENE
+amylin	I-GENE
+promoter	I-GENE
+in	O
+both	O
+fibroblast	O
+and	O
+islet	O
+cell	O
+lines	O
+.	O
+
+Although	O
+isl	B-GENE
+-	I-GENE
+1	I-GENE
+binds	O
+to	O
+both	O
+the	O
+insulin	B-GENE
+and	O
+amylin	B-GENE
+gene	I-GENE
+promoter	I-GENE
+elements	I-GENE
+in	O
+vitro	O
+,	O
+these	O
+sequences	O
+display	O
+marked	O
+differences	O
+in	O
+their	O
+relative	O
+transcriptional	O
+properties	O
+when	O
+ligated	O
+adjacent	O
+to	O
+a	O
+heterologous	O
+promoter	O
+and	O
+transfected	O
+into	O
+InR1	O
+-	O
+G9	O
+islet	O
+cells	O
+.	O
+
+It	O
+is	O
+likely	O
+that	O
+other	O
+pathways	O
+involve	O
+alternate	O
+signal	O
+transduction	O
+events	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+calcium	O
+mobilization	O
+)	O
+and	O
+promoter	O
+response	O
+elements	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+SRE	O
+)	O
+.	O
+
+The	O
+CD4	B-GENE
+count	O
+at	O
+which	O
+remission	O
+occurs	O
+may	O
+reflect	O
+severe	O
+immunodeficiency	O
+such	O
+that	O
+risk	O
+for	O
+AIDS	O
+-	O
+related	O
+infection	O
+is	O
+high	O
+.	O
+
+Although	O
+diagnostic	O
+laparoscopy	O
+is	O
+still	O
+considered	O
+the	O
+standard	O
+reference	O
+in	O
+the	O
+diagnosis	O
+of	O
+ectopic	O
+pregnancy	O
+(	O
+EP	O
+)	O
+,	O
+use	O
+of	O
+high	O
+-	O
+resolution	O
+endovaginal	O
+sonography	O
+,	O
+in	O
+conjunction	O
+with	O
+qualitative	O
+serum	O
+assays	O
+of	O
+the	O
+beta	O
+subunit	O
+of	O
+human	B-GENE
+chorionic	I-GENE
+gonadotropin	I-GENE
+(	O
+beta	B-GENE
+-	I-GENE
+hCG	I-GENE
+)	O
+,	O
+allows	O
+detection	O
+of	O
+earlier	O
+and	O
+smaller	O
+EPs	O
+.	O
+
+Bifunctionality	O
+of	O
+the	O
+AcMNPV	B-GENE
+homologous	I-GENE
+region	I-GENE
+sequence	I-GENE
+(	O
+hr1	B-GENE
+)	O
+:	O
+enhancer	O
+and	O
+ori	O
+functions	O
+have	O
+different	O
+sequence	O
+requirements	O
+.	O
+
+Neither	O
+CES1	B-GENE
+nor	O
+CES4	B-GENE
+is	O
+essential	O
+for	O
+cell	O
+growth	O
+,	O
+and	O
+a	O
+double	O
+deletion	O
+mutant	O
+is	O
+viable	O
+.	O
+
+Their	O
+use	O
+established	O
+that	O
+the	O
+BrAAP	O
+activity	O
+catalyzed	O
+both	O
+a	O
+postproline	O
+and	O
+a	O
+postglutamate	O
+cleavage	O
+and	O
+therefore	O
+has	O
+a	O
+broader	O
+specificity	O
+than	O
+previously	O
+recognized	O
+.	O
+
+To	O
+explore	O
+the	O
+functional	O
+significance	O
+of	O
+these	O
+subdomains	O
+in	O
+PRL	B-GENE
+binding	O
+and	O
+signal	O
+transduction	O
+,	O
+deletion	O
+mutants	O
+of	O
+S1	O
+or	O
+/	O
+and	O
+S2	O
+subdomains	O
+were	O
+constructed	O
+.	O
+
+A	O
+stable	O
+heterologous	O
+cell	O
+line	O
+containing	O
+the	O
+mouse	B-GENE
+TRH	I-GENE
+receptor	I-GENE
+was	O
+constructed	O
+by	O
+transfection	O
+of	O
+nonexcitable	O
+293	O
+cells	O
+,	O
+which	O
+lack	O
+L	O
+channel	O
+activity	O
+.	O
+
+To	O
+understand	O
+further	O
+the	O
+expression	O
+and	O
+regulation	O
+of	O
+the	O
+V1aR	B-GENE
+,	O
+we	O
+now	O
+describe	O
+the	O
+genomic	O
+characteristics	O
+,	O
+tissue	O
+expression	O
+,	O
+chromosomal	O
+localization	O
+,	O
+and	O
+regional	O
+mapping	O
+of	O
+the	O
+human	B-GENE
+V1aR	I-GENE
+gene	I-GENE
+,	O
+AVPR1A	B-GENE
+.	O
+
+The	O
+final	O
+predicted	O
+structure	O
+has	O
+an	O
+overall	O
+backbone	O
+deviation	O
+of	O
+0	O
+.	O
+7	O
+A	O
+from	O
+that	O
+of	O
+ras	B-GENE
+-	O
+p21	B-GENE
+.	O
+
+Genomic	O
+organization	O
+of	O
+the	O
+human	B-GENE
+beta	I-GENE
+-	I-GENE
+catenin	I-GENE
+gene	I-GENE
+(	O
+CTNNB1	B-GENE
+)	O
+.	O
+
+Furthermore	O
+,	O
+although	O
+the	O
+regional	O
+distribution	O
+of	O
+lean	O
+tissue	O
+mass	O
+in	O
+the	O
+trunk	O
+and	O
+legs	O
+remained	O
+fairly	O
+constant	O
+at	O
+different	O
+pubertal	O
+stages	O
+,	O
+the	O
+regional	O
+distribution	O
+of	O
+fat	O
+was	O
+altered	O
+significantly	O
+,	O
+becoming	O
+more	O
+central	O
+and	O
+less	O
+peripheral	O
+.	O
+
+Thus	O
+,	O
+the	O
+predicted	O
+CD30v	B-GENE
+protein	I-GENE
+retains	O
+most	O
+of	O
+the	O
+cytoplasmic	O
+region	O
+,	O
+but	O
+lacks	O
+the	O
+extracellular	O
+and	O
+transmembrane	O
+domains	O
+.	O
+
+Constitutive	O
+phosphorylation	O
+of	O
+the	O
+CD30v	B-GENE
+protein	I-GENE
+was	O
+demonstrated	O
+by	O
+in	O
+vitro	O
+labeling	O
+with	O
+[	O
+32P	O
+]	O
+.	O
+
+17	O
+.	O
+5	O
+%	O
+of	O
+cycles	O
+)	O
+.	O
+
+We	O
+report	O
+here	O
+the	O
+discovery	O
+of	O
+a	O
+new	O
+actin	B-GENE
+-	I-GENE
+related	I-GENE
+gene	I-GENE
+in	O
+this	O
+organism	O
+,	O
+which	O
+we	O
+have	O
+named	O
+ACT4	B-GENE
+.	O
+
+Two	O
+of	O
+the	O
+ORFs	O
+are	O
+completely	O
+internal	O
+to	O
+longer	O
+ones	O
+and	O
+a	O
+third	O
+is	O
+partially	O
+embedded	O
+in	O
+G2850	B-GENE
+.	O
+
+MVR	O
+typing	O
+of	O
+rare	O
+-	O
+length	O
+alleles	O
+indicates	O
+that	O
+they	O
+are	O
+comprised	O
+of	O
+disorganized	O
+sequences	O
+,	O
+although	O
+they	O
+usually	O
+bear	O
+a	O
+resemblance	O
+to	O
+one	O
+of	O
+the	O
+common	O
+alleles	O
+at	O
+the	O
+5	O
+'	O
+-	O
+most	O
+end	O
+.	O
+
+Plasmid	O
+pAL618	O
+contains	O
+the	O
+genetic	O
+determinants	O
+for	O
+H2	O
+uptake	O
+(	O
+hup	B-GENE
+)	O
+from	O
+Rhizobium	O
+leguminosarum	O
+bv	O
+.	O
+viciae	O
+,	O
+including	O
+a	O
+cluster	O
+of	O
+17	O
+genes	O
+named	O
+hupSLCDEFGHIJK	B-GENE
+-	I-GENE
+hypABFCDE	I-GENE
+.	O
+
+An	O
+open	O
+-	O
+label	O
+,	O
+placebo	O
+-	O
+controlled	O
+,	O
+randomized	O
+,	O
+two	O
+-	O
+way	O
+crossover	O
+study	O
+was	O
+performed	O
+in	O
+12	O
+healthy	O
+volunteers	O
+(	O
+between	O
+20	O
+and	O
+44	O
+years	O
+of	O
+age	O
+)	O
+to	O
+assess	O
+the	O
+effect	O
+of	O
+orlistat	O
+,	O
+a	O
+gastrointestinal	B-GENE
+lipase	I-GENE
+inhibitor	O
+that	O
+reduces	O
+dietary	O
+fat	O
+absorption	O
+and	O
+is	O
+being	O
+developed	O
+for	O
+weight	O
+control	O
+in	O
+obesity	O
+,	O
+on	O
+the	O
+absorption	O
+of	O
+vitamins	O
+A	O
+and	O
+E	O
+.	O
+
+Tilmicosin	O
+is	O
+a	O
+novel	O
+macrolide	O
+antibiotic	O
+developed	O
+for	O
+exclusive	O
+use	O
+in	O
+veterinary	O
+medicine	O
+.	O
+
+Effect	O
+of	O
+nitrous	O
+oxide	O
+(	O
+N2O	O
+)	O
+on	O
+the	O
+somatosympathetic	O
+A	O
+-	O
+and	O
+C	O
+-	O
+reflexes	O
+was	O
+investigated	O
+using	O
+artificially	O
+ventilated	O
+rats	O
+anesthetized	O
+with	O
+alpha	O
+-	O
+chloralose	O
+and	O
+urethane	O
+.	O
+
+Restriction	O
+enzyme	O
+mapping	O
+and	O
+Southern	O
+analysis	O
+indicated	O
+further	O
+that	O
+the	O
+human	B-GENE
+MZF	I-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+is	O
+a	O
+single	O
+-	O
+copy	O
+gene	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+Swi4	B-GENE
+and	O
+Swi6	B-GENE
+cell	O
+viability	O
+is	O
+lost	O
+,	O
+but	O
+can	O
+be	O
+regained	O
+by	O
+ectopic	O
+expression	O
+of	O
+the	O
+G1	B-GENE
+cyclin	I-GENE
+encoding	I-GENE
+genes	I-GENE
+,	O
+CLN1	B-GENE
+or	O
+CLN2	B-GENE
+.	O
+
+The	O
+detection	O
+ratio	O
+peaked	O
+at	O
+ages	O
+30	O
+to	O
+34	O
+and	O
+decreased	O
+heavily	O
+during	O
+the	O
+next	O
+15	O
+years	O
+of	O
+age	O
+.	O
+
+How	O
+many	O
+embryos	O
+to	O
+transfer	O
+in	O
+patients	O
+undergoing	O
+IVF	O
+?	O
+
+The	O
+nonconsensus	O
+TATA	O
+box	O
+in	O
+promoter	O
+B	O
+plays	O
+a	O
+more	O
+important	O
+role	O
+in	O
+promoter	O
+activity	O
+than	O
+the	O
+TATA	O
+box	O
+in	O
+promoter	O
+A	O
+.	O
+
+These	O
+properties	O
+indicate	O
+that	O
+Gle1	B-GENE
+is	O
+an	O
+RNA	O
+-	O
+export	O
+factor	O
+and	O
+that	O
+Rev	B-GENE
+may	O
+mediate	O
+viral	O
+RNA	O
+export	O
+by	O
+mimicking	O
+the	O
+function	O
+of	O
+Gle1	B-GENE
+.	O
+
+Demispan	O
+is	O
+a	O
+reliable	O
+and	O
+reproducible	O
+measure	O
+of	O
+stature	O
+in	O
+the	O
+elderly	O
+.	O
+
+Two	O
+techniques	O
+based	O
+on	O
+assay	O
+coefficients	O
+of	O
+variation	O
+were	O
+employed	O
+to	O
+characterize	O
+a	O
+normal	O
+circadian	O
+pattern	O
+of	O
+cortisol	O
+.	O
+
+A	O
+system	O
+is	O
+described	O
+in	O
+which	O
+the	O
+volume	O
+flow	O
+rate	O
+of	O
+blood	O
+in	O
+a	O
+vessel	O
+is	O
+determined	O
+using	O
+transverse	O
+colour	O
+Doppler	O
+ultrasound	O
+imaging	O
+.	O
+
+The	O
+enzyme	O
+activities	O
+studied	O
+are	O
+important	O
+elements	O
+in	O
+the	O
+pathophysiology	O
+of	O
+dental	O
+caries	O
+and	O
+may	O
+even	O
+be	O
+addressed	O
+as	O
+virulence	O
+factors	O
+.	O
+
+In	O
+lean	O
+mice	O
+,	O
+the	O
+fat	O
+/	O
+water	O
+intensity	O
+ratio	O
+was	O
+about	O
+1	O
+:	O
+4	O
+,	O
+about	O
+half	O
+that	O
+in	O
+normal	O
+mice	O
+.	O
+
+Pharmacokinetic	O
+parameters	O
+were	O
+similar	O
+to	O
+values	O
+given	O
+in	O
+the	O
+literature	O
+for	O
+intravenous	O
+(	O
+IV	O
+)	O
+or	O
+intraarterial	O
+(	O
+IA	O
+)	O
+bolus	O
+MMC	O
+injections	O
+(	O
+Tmax	O
+=	O
+7	O
+.	O
+0	O
+min	O
+following	O
+the	O
+beginning	O
+of	O
+MMC	O
+infusion	O
+,	O
+Vss	O
+=	O
+0	O
+.	O
+57	O
+1	O
+/	O
+kg	O
+,	O
+C1	O
+=	O
+8	O
+.	O
+9	O
+ml	O
+/	O
+min	O
+.	O
+kg	O
+,	O
+T1	O
+/	O
+2	O
+alpha	O
+=	O
+8	O
+.	O
+3	O
+min	O
+,	O
+T1	O
+/	O
+2	O
+beta	O
+=	O
+58	O
+.	O
+6	O
+min	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+identified	O
+four	O
+distinct	O
+E2F	B-GENE
+complexes	I-GENE
+present	O
+in	O
+aged	O
+and	O
+senescent	O
+normal	O
+,	O
+human	O
+diploid	O
+fibroblasts	O
+.	O
+
+This	O
+paper	O
+gives	O
+an	O
+overview	O
+of	O
+the	O
+global	O
+pattern	O
+of	O
+casualties	O
+in	O
+earthquakes	O
+which	O
+occurred	O
+during	O
+the	O
+30	O
+-	O
+month	O
+period	O
+from	O
+1	O
+September	O
+1993	O
+to	O
+29	O
+February	O
+1996	O
+.	O
+
+If	O
+we	O
+apply	O
+the	O
+finding	O
+of	O
+non	O
+-	O
+visualization	O
+of	O
+the	O
+GB	O
+at	O
+4	O
+h	O
+post	O
+injection	O
+as	O
+the	O
+criterion	O
+for	O
+the	O
+diagnosis	O
+of	O
+AC	O
+,	O
+the	O
+diagnostic	O
+accuracy	O
+was	O
+only	O
+40	O
+.	O
+7	O
+%	O
+(	O
+11	O
+/	O
+27	O
+)	O
+.	O
+
+Alternative	O
+processing	O
+of	O
+the	O
+tryptophanyl	B-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+mRNA	I-GENE
+from	O
+interferon	B-GENE
+-	O
+treated	O
+human	O
+cells	O
+.	O
+
+Evidence	O
+for	O
+the	O
+promoting	O
+role	O
+of	O
+the	O
+intra	B-GENE
+-	I-GENE
+uterine	I-GENE
+kinin	I-GENE
+release	O
+in	O
+the	O
+development	O
+of	O
+late	O
+hypertonic	O
+saline	O
+-	O
+induced	O
+abortion	O
+.	O
+
+This	O
+GAP	B-GENE
+activity	O
+was	O
+observed	O
+in	O
+3T3	O
+-	O
+L1	O
+adipocyte	O
+lysates	O
+,	O
+and	O
+was	O
+able	O
+to	O
+accelerate	O
+the	O
+hydrolysis	O
+of	O
+the	O
+[	O
+alpha	O
+-	O
+32P	O
+]	O
+GTP	O
+bound	O
+to	O
+GST	B-GENE
+-	O
+Rab4	B-GENE
+into	O
+[	O
+alpha	O
+-	O
+32P	O
+]	O
+GDP	O
+.	O
+
+CONCLUSION	O
+:	O
+During	O
+chronic	O
+treatment	O
+,	O
+the	O
+haemodynamic	O
+response	O
+to	O
+oral	O
+cilazapril	O
+was	O
+attenuated	O
+,	O
+indicating	O
+that	O
+continued	O
+clinical	O
+improvement	O
+in	O
+patients	O
+with	O
+CHF	O
+on	O
+CLZ	O
+is	O
+independent	O
+of	O
+to	O
+its	O
+acute	O
+haemodynamic	O
+effects	O
+.	O
+
+We	O
+conclude	O
+that	O
+,	O
+in	O
+AIDS	O
+patients	O
+with	O
+cryptococcosis	O
+,	O
+tolerance	O
+to	O
+ILd	O
+-	O
+AmB	O
+was	O
+acceptable	O
+when	O
+the	O
+daily	O
+dosage	O
+did	O
+not	O
+exceed	O
+1	O
+mg	O
+/	O
+kg	O
+,	O
+but	O
+the	O
+higher	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+daily	O
+dosage	O
+was	O
+associated	O
+with	O
+an	O
+unacceptable	O
+rate	O
+of	O
+nephrotoxicity	O
+.	O
+
+Moreover	O
+,	O
+the	O
+second	O
+RCC1	B-GENE
+-	I-GENE
+like	I-GENE
+motif	I-GENE
+located	O
+at	O
+the	O
+amino	O
+-	O
+terminus	O
+of	O
+p619	B-GENE
+stimulates	O
+guanine	O
+nucleotide	O
+exchange	O
+on	O
+ARF1	B-GENE
+and	O
+on	O
+members	O
+of	O
+the	O
+related	O
+Rab	B-GENE
+proteins	I-GENE
+,	O
+but	O
+not	O
+on	O
+other	O
+small	B-GENE
+GTP	I-GENE
+binding	I-GENE
+proteins	I-GENE
+such	O
+as	O
+Ran	B-GENE
+or	O
+R	B-GENE
+-	I-GENE
+Ras2	I-GENE
+/	O
+TC21	B-GENE
+.	O
+
+The	O
+reconstituted	O
+RNA	B-GENE
+polymerases	I-GENE
+containing	O
+the	O
+mutant	O
+alpha	O
+subunits	O
+were	O
+examined	O
+for	O
+their	O
+response	O
+to	O
+transcription	O
+activation	O
+by	O
+cAMP	B-GENE
+-	I-GENE
+CRP	I-GENE
+and	O
+the	O
+rrnBP1	B-GENE
+UP	I-GENE
+element	I-GENE
+.	O
+
+Transcription	O
+factor	O
+recognition	O
+surface	O
+on	O
+the	O
+RNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+subunit	I-GENE
+is	O
+involved	O
+in	O
+contact	O
+with	O
+the	O
+DNA	O
+enhancer	O
+element	O
+.	O
+
+Consistent	O
+with	O
+this	O
+similarity	O
+,	O
+the	O
+cdc28	B-GENE
+-	O
+P8	O
+mutant	O
+accumulates	O
+unspliced	O
+precursors	O
+at	O
+the	O
+restrictive	O
+temperature	O
+.	O
+
+A	O
+decrease	O
+of	O
+erythrocyte	O
+Mn	O
+with	O
+age	O
+,	O
+expressed	O
+in	O
+nmol	O
+/	O
+L	O
+,	O
+was	O
+noted	O
+(	O
+p	O
+<	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+Cloning	O
+and	O
+sequence	O
+analyses	O
+revealed	O
+a	O
+second	O
+cDNA	O
+with	O
+a	O
+95	O
+-	O
+nt	O
+deletion	O
+in	O
+the	O
+region	O
+coding	O
+for	O
+the	O
+putative	O
+second	O
+intracellular	O
+loop	O
+and	O
+the	O
+fourth	O
+transmembrane	O
+domain	O
+of	O
+the	O
+5	B-GENE
+-	I-GENE
+HT2C	I-GENE
+-	I-GENE
+R	I-GENE
+.	O
+
+Expression	O
+of	O
+thymidine	B-GENE
+kinase	I-GENE
+gene	I-GENE
+in	O
+normal	O
+human	O
+diploid	O
+cells	O
+is	O
+both	O
+cell	O
+cycle	O
+-	O
+and	O
+age	O
+-	O
+dependent	O
+and	O
+appears	O
+to	O
+be	O
+transcriptionally	O
+regulated	O
+.	O
+
+The	O
+minimum	O
+inhibitory	O
+concentrations	O
+(	O
+MICs	O
+)	O
+of	O
+ketoconazole	O
+,	O
+miconazole	O
+,	O
+itraconazole	O
+,	O
+fluconazole	O
+,	O
+and	O
+amphotericin	O
+B	O
+were	O
+significantly	O
+influenced	O
+by	O
+the	O
+inoculum	O
+size	O
+,	O
+regardless	O
+of	O
+the	O
+techniques	O
+used	O
+.	O
+
+These	O
+bacteria	O
+produce	O
+and	O
+export	O
+proteins	O
+capable	O
+of	O
+specific	O
+interactions	O
+with	O
+key	O
+mammalian	O
+cell	O
+regulatory	O
+molecules	O
+in	O
+order	O
+to	O
+derail	O
+the	O
+normal	O
+functions	O
+of	O
+the	O
+cells	O
+.	O
+
+Thus	O
+,	O
+although	O
+p28	B-GENE
+may	O
+play	O
+only	O
+a	O
+limited	O
+role	O
+during	O
+the	O
+early	O
+embryonic	O
+cleavages	O
+,	O
+it	O
+may	O
+function	O
+later	O
+in	O
+development	O
+to	O
+establish	O
+a	O
+somatic	O
+type	O
+of	O
+cell	O
+cycle	O
+.	O
+
+The	O
+main	O
+aim	O
+of	O
+the	O
+contribution	O
+,	O
+which	O
+opens	O
+an	O
+arena	O
+for	O
+discussion	O
+on	O
+the	O
+Rivista	O
+dell	O
+'	O
+Infermiere	O
+is	O
+to	O
+critically	O
+appraise	O
+published	O
+research	O
+works	O
+focusing	O
+both	O
+on	O
+strengths	O
+and	O
+novelty	O
+and	O
+weaknesses	O
+in	O
+the	O
+hypothesis	O
+formulation	O
+,	O
+methods	O
+and	O
+instruments	O
+used	O
+,	O
+discussion	O
+of	O
+results	O
+.	O
+
+Moreover	O
+,	O
+it	O
+also	O
+discusses	O
+the	O
+effects	O
+of	O
+antihypertensive	O
+drugs	O
+currently	O
+regarded	O
+as	O
+first	O
+-	O
+choice	O
+agents	O
+,	O
+i	O
+.	O
+e	O
+.	O
+calcium	O
+antagonists	O
+and	O
+the	O
+angiotensin	B-GENE
+converting	I-GENE
+enzyme	I-GENE
+inhibitors	O
+,	O
+on	O
+intrarenal	O
+hemodynamics	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+the	O
+observed	O
+clinical	O
+phenomena	O
+in	O
+response	O
+to	O
+morphine	O
+can	O
+be	O
+explained	O
+by	O
+differences	O
+in	O
+expression	O
+and	O
+sensitivity	O
+of	O
+some	O
+opioid	B-GENE
+receptor	I-GENE
+subtypes	O
+in	O
+migraine	O
+.	O
+
+Previous	O
+studies	O
+demonstrated	O
+that	O
+the	O
+flavin	B-GENE
+-	I-GENE
+containing	I-GENE
+monooxygenases	I-GENE
+(	O
+FMO	B-GENE
+)	O
+are	O
+expressed	O
+in	O
+a	O
+tissue	O
+-	O
+specific	O
+manner	O
+.	O
+
+Thus	O
+,	O
+despite	O
+the	O
+potential	O
+for	O
+common	O
+regulatory	O
+mechanisms	O
+,	O
+the	O
+available	O
+evidence	O
+indicates	O
+that	O
+the	O
+Mtx	B-GENE
+minimal	I-GENE
+promoter	I-GENE
+does	O
+not	O
+significantly	O
+affect	O
+Thbs3	B-GENE
+gene	I-GENE
+expression	O
+.	O
+
+MSSP	B-GENE
+proteins	I-GENE
+have	O
+been	O
+identified	O
+by	O
+their	O
+binding	O
+to	O
+an	O
+upstream	O
+element	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+.	O
+
+Gene	B-GENE
+1	I-GENE
+has	O
+been	O
+completely	O
+sequenced	O
+.	O
+
+B	B-GENE
+cell	I-GENE
+antigen	I-GENE
+receptor	I-GENE
+(	O
+BCR	B-GENE
+)	O
+-	O
+induced	O
+apoptosis	O
+in	O
+the	O
+WEHI	O
+-	O
+231	O
+B	O
+lymphoma	O
+cell	O
+line	O
+can	O
+be	O
+prevented	O
+by	O
+engaging	O
+CD40	B-GENE
+.	O
+
+Both	O
+alleles	O
+are	O
+functionally	O
+expressed	O
+and	O
+are	O
+distributed	O
+within	O
+CD4	B-GENE
++	O
+/	O
+CD8	B-GENE
++	O
+T	O
+cell	O
+subsets	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+LvUSF2	B-GENE
+is	O
+nearly	O
+identical	O
+to	O
+LvUSF1	B-GENE
+except	O
+at	O
+the	O
+amino	O
+end	O
+,	O
+where	O
+they	O
+are	O
+sharply	O
+divergent	O
+.	O
+
+ECM	O
+disruption	O
+in	O
+Lytechinus	O
+embryos	O
+caused	O
+a	O
+relative	O
+drop	O
+in	O
+USF	B-GENE
+RNA	I-GENE
+accumulation	O
+levels	O
+to	O
+approximately	O
+60	O
+%	O
+of	O
+control	O
+embryos	O
+,	O
+while	O
+LpS1	B-GENE
+RNA	I-GENE
+accumulation	O
+levels	O
+dropped	O
+to	O
+less	O
+than	O
+5	O
+%	O
+.	O
+
+Five	O
+of	O
+these	O
+eight	O
+patients	O
+in	O
+group	O
+II	O
+also	O
+received	O
+8	O
+-	O
+in	O
+-	O
+1	O
+chemotherapy	O
+.	O
+
+Sixty	O
+days	O
+after	O
+the	O
+intervention	O
+,	O
+twitch	O
+and	O
+tetanic	O
+tensions	O
+remained	O
+dependent	O
+upon	O
+the	O
+extracellular	O
+Ca2	O
++	O
+concentration	O
+(	O
+[	O
+Ca	O
+]	O
+o	O
+)	O
+both	O
+in	O
+groups	O
+A	O
+and	O
+B	O
+.	O
+
+Recently	O
+,	O
+a	O
+distantly	O
+related	O
+UmuC	B-GENE
+-	I-GENE
+homolog	I-GENE
+,	O
+DinB	B-GENE
+,	O
+has	O
+also	O
+been	O
+identified	O
+in	O
+E	O
+.	O
+coli	O
+.	O
+
+To	O
+study	O
+the	O
+regulation	O
+of	O
+mdr2	B-GENE
+expression	O
+,	O
+the	O
+promoter	O
+of	O
+the	O
+mdr2	B-GENE
+gene	I-GENE
+has	O
+been	O
+isolated	O
+from	O
+a	O
+murine	O
+vinblastine	O
+-	O
+resistant	O
+cell	O
+line	O
+,	O
+J7	O
+.	O
+V2	O
+-	O
+1	O
+,	O
+and	O
+characterized	O
+.	O
+
+The	O
+amplification	O
+was	O
+achieved	O
+using	O
+two	O
+primers	O
+which	O
+correspond	O
+to	O
+TRH	B-GENE
+progenitor	I-GENE
+sequence	I-GENE
+(	O
+Lys	O
+/	O
+Arg	O
+-	O
+Arg	O
+-	O
+Gln	O
+-	O
+His	O
+-	O
+Pro	O
+-	O
+Gly	O
+-	O
+Lys	O
+/	O
+Arg	O
+-	O
+Arg	O
+)	O
+.	O
+
+The	O
+intranodal	O
+mesothelial	O
+cells	O
+occupied	O
+the	O
+sinusoids	O
+of	O
+the	O
+lymph	O
+nodes	O
+and	O
+were	O
+initially	O
+suspected	O
+of	O
+being	O
+metastatic	O
+from	O
+the	O
+ovarian	O
+tumor	O
+in	O
+each	O
+case	O
+.	O
+
+The	O
+gene	B-GENE
+ccpA	I-GENE
+encoding	O
+the	O
+catabolite	B-GENE
+control	I-GENE
+protein	I-GENE
+CcpA	I-GENE
+of	O
+Staphylococcus	O
+xylosus	O
+has	O
+been	O
+cloned	O
+and	O
+characterized	O
+.	O
+
+An	O
+InlC	B-GENE
+deletion	I-GENE
+mutant	I-GENE
+shows	O
+reduced	O
+virulence	O
+when	O
+tested	O
+in	O
+an	O
+intravenous	O
+mouse	O
+model	O
+,	O
+but	O
+intracellular	O
+replication	O
+of	O
+the	O
+mutant	O
+in	O
+Caco	O
+-	O
+2	O
+and	O
+J774	O
+cells	O
+appears	O
+to	O
+be	O
+comparable	O
+with	O
+that	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+strain	O
+.	O
+
+Thus	O
+,	O
+the	O
+N	B-GENE
+-	O
+Nus	B-GENE
+complex	O
+may	O
+be	O
+affected	O
+through	O
+contacts	O
+with	O
+the	O
+CTD	O
+of	O
+the	O
+alpha	O
+subunit	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+,	O
+as	O
+is	O
+a	O
+group	O
+of	O
+regulatory	O
+proteins	O
+that	O
+influences	O
+initiation	O
+of	O
+transcription	O
+.	O
+
+Administration	O
+of	O
+RIFA	O
+at	O
+200	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+in	O
+combination	O
+with	O
+ATO	O
+at	O
+100	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+resulted	O
+in	O
+a	O
+marked	O
+prolongation	O
+of	O
+survival	O
+compared	O
+with	O
+that	O
+for	O
+mice	O
+that	O
+received	O
+ATO	O
+or	O
+RIFA	O
+alone	O
+.	O
+
+Two	O
+of	O
+seven	O
+initiation	O
+sites	O
+were	O
+flanked	O
+by	O
+a	O
+sequence	O
+homologous	O
+to	O
+the	O
+consensus	O
+promoter	O
+motif	O
+that	O
+includes	O
+the	O
+CRTA	O
+motif	O
+(	O
+where	O
+R	O
+is	O
+A	O
+or	O
+G	O
+)	O
+of	O
+the	O
+rice	O
+mitochondrion	O
+.	O
+
+Selection	O
+using	O
+SC	O
+EPD	O
+was	O
+more	O
+effective	O
+than	O
+phenotypic	O
+selection	O
+in	O
+reducing	O
+age	O
+at	O
+puberty	O
+in	O
+daughters	O
+.	O
+
+Sodium	O
+polystyrene	O
+sulfonate	O
+treatment	O
+for	O
+lithium	O
+toxicity	O
+:	O
+effects	O
+on	O
+serum	O
+potassium	O
+concentrations	O
+.	O
+
+The	O
+mammalian	B-GENE
+homeodomain	I-GENE
+proteins	I-GENE
+encoded	O
+by	O
+Hox	B-GENE
+genes	I-GENE
+play	O
+an	O
+important	O
+role	O
+in	O
+embryonic	O
+development	O
+by	O
+providing	O
+positional	O
+queues	O
+which	O
+define	O
+developmental	O
+identities	O
+along	O
+the	O
+anteroposterior	O
+axis	O
+of	O
+developing	O
+organisms	O
+.	O
+
+Interferon	B-GENE
+stimulated	I-GENE
+gene	I-GENE
+factor	I-GENE
+3	I-GENE
+(	O
+ISGF3	B-GENE
+)	O
+is	O
+a	O
+trimeric	O
+transcription	O
+factor	O
+activated	O
+on	O
+treatment	O
+of	O
+cells	O
+with	O
+interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	I-GENE
+beta	I-GENE
+(	O
+type	B-GENE
+I	I-GENE
+IFNs	I-GENE
+)	O
+.	O
+
+The	O
+TYAC	O
+/	O
+P1	O
+resource	O
+,	O
+derivative	O
+STSs	O
+,	O
+and	O
+polymorphisms	O
+constitute	O
+an	O
+enabling	O
+resource	O
+to	O
+further	O
+studies	O
+of	O
+telomere	O
+structure	O
+and	O
+function	O
+and	O
+a	O
+means	O
+for	O
+physical	O
+and	O
+genetic	O
+map	O
+integration	O
+and	O
+closure	O
+.	O
+
+Confirmatory	O
+statistics	O
+included	O
+item	O
+2	O
+of	O
+the	O
+Clinical	O
+Global	O
+Impression	O
+(	O
+CGI	O
+)	O
+,	O
+the	O
+total	O
+score	O
+of	O
+the	O
+Sandoz	O
+Clinical	O
+Assessment	O
+Geriatric	O
+(	O
+SCAG	O
+)	O
+scale	O
+,	O
+the	O
+subscale	O
+'	O
+need	O
+for	O
+help	O
+'	O
+of	O
+the	O
+nurse	O
+'	O
+s	O
+rating	O
+of	O
+geriatric	O
+patients	O
+(	O
+Beurteilungsskala	O
+fur	O
+geriatrische	O
+Patienten	O
+;	O
+BGP	O
+)	O
+and	O
+the	O
+total	O
+score	O
+of	O
+the	O
+Short	O
+Cognitive	O
+Performance	O
+Test	O
+(	O
+Syndrom	O
+-	O
+Kurztest	O
+;	O
+SKT	O
+)	O
+.	O
+
+Three	O
+mutants	O
+were	O
+isolated	O
+from	O
+the	O
+widely	O
+used	O
+strain	O
+,	O
+PAO1	O
+.	O
+
+As	O
+extensively	O
+examined	O
+with	O
+the	O
+myogenin	B-GENE
+promoter	I-GENE
+,	O
+presence	O
+of	O
+one	O
+or	O
+multiple	O
+copies	O
+of	O
+Me	B-GENE
+in	O
+the	O
+vectors	O
+elevated	O
+the	O
+expression	O
+activity	O
+in	O
+myotubes	O
+by	O
+4	O
+.	O
+5	O
+-	O
+to	O
+19	O
+-	O
+fold	O
+over	O
+those	O
+without	O
+Me	B-GENE
+,	O
+but	O
+not	O
+significantly	O
+in	O
+myoblasts	O
+.	O
+
+We	O
+conclude	O
+that	O
+common	O
+upstream	O
+signals	O
+cause	O
+activation	O
+of	O
+Ras	B-GENE
+and	O
+TC21	B-GENE
+,	O
+but	O
+activated	O
+TC21	B-GENE
+controls	O
+cell	O
+growth	O
+via	O
+distinct	O
+Raf	B-GENE
+-	O
+independent	O
+downstream	O
+signaling	O
+pathways	O
+.	O
+
+Fission	B-GENE
+yeast	I-GENE
+mal2	I-GENE
++	I-GENE
+is	O
+required	O
+for	O
+chromosome	O
+segregation	O
+.	O
+
+Selection	O
+was	O
+based	O
+on	O
+expression	O
+of	O
+an	O
+integrated	O
+DNA	O
+fragment	O
+containing	O
+the	O
+con	B-GENE
+-	I-GENE
+10	I-GENE
+promoter	I-GENE
+-	I-GENE
+regulatory	I-GENE
+region	I-GENE
+followed	O
+by	O
+the	O
+initial	O
+segment	O
+of	O
+the	O
+con	B-GENE
+-	I-GENE
+10	I-GENE
+open	I-GENE
+reading	I-GENE
+frame	I-GENE
+fused	O
+in	O
+frame	O
+with	O
+the	O
+bacterial	B-GENE
+hygromycin	I-GENE
+B	I-GENE
+phosphotransferase	I-GENE
+structural	I-GENE
+gene	I-GENE
+(	O
+con10	B-GENE
+'	I-GENE
+-	I-GENE
+'	I-GENE
+hph	I-GENE
+)	O
+.	O
+
+Mutations	O
+at	O
+two	O
+neighboring	O
+sites	O
+,	O
+serine	O
+242	O
+and	O
+threonine	O
+255	O
+,	O
+exacerbated	O
+the	O
+effect	O
+.	O
+
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+acts	O
+as	O
+a	O
+transcriptional	O
+activator	O
+,	O
+while	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+acts	O
+as	O
+a	O
+repressor	O
+.	O
+
+In	O
+contrast	O
+,	O
+cotransfection	O
+of	O
+TFIIB	B-GENE
+and	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+into	O
+NIH	O
+3T3	O
+cells	O
+resulted	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+repression	O
+of	O
+promoter	O
+activation	O
+which	O
+occurred	O
+in	O
+a	O
+TATA	O
+-	O
+dependent	O
+manner	O
+.	O
+
+The	O
+requirement	O
+of	O
+Tyr	O
+-	O
+19	O
+dephosphorylation	O
+for	O
+spindle	O
+assembly	O
+is	O
+also	O
+observed	O
+under	O
+conditions	O
+in	O
+which	O
+spindle	O
+formation	O
+is	O
+independent	O
+of	O
+mitosis	O
+,	O
+suggesting	O
+that	O
+the	O
+involvement	O
+of	O
+Cdc28	B-GENE
+/	O
+Clb	B-GENE
+kinase	O
+in	O
+SPB	O
+separation	O
+is	O
+direct	O
+.	O
+
+Expression	O
+of	O
+the	O
+proapoptotic	B-GENE
+protein	I-GENE
+Bax	I-GENE
+under	O
+the	O
+control	O
+of	O
+a	O
+GAL10	B-GENE
+promoter	I-GENE
+in	O
+Saccharomyces	O
+cerevisiae	O
+resulted	O
+in	O
+galactose	O
+-	O
+inducible	O
+cell	O
+death	O
+.	O
+
+This	O
+technique	O
+was	O
+employed	O
+in	O
+12	O
+patients	O
+with	O
+a	O
+unicameral	O
+bone	O
+cyst	O
+.	O
+
+The	O
+amino	O
+-	O
+terminal	O
+region	O
+of	O
+E1A	B-GENE
+binds	O
+several	O
+high	O
+molecular	O
+weight	O
+proteins	O
+and	O
+inhibits	O
+the	O
+transcriptional	O
+coactivator	O
+function	O
+of	O
+p300	B-GENE
+and	O
+the	O
+homologous	O
+cAMP	B-GENE
+response	I-GENE
+element	I-GENE
+(	I-GENE
+CRE	I-GENE
+)	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+Transient	O
+transfection	O
+assays	O
+using	O
+reporter	O
+gene	O
+constructs	O
+containing	O
+various	O
+lengths	O
+of	O
+the	O
+5	B-GENE
+'	I-GENE
+mdr1b	I-GENE
+sequences	I-GENE
+revealed	O
+that	O
+the	O
+sequence	O
+located	O
+between	O
+-	O
+247	O
+to	O
+-	O
+126	O
+bp	O
+was	O
+important	O
+for	O
+the	O
+expression	O
+of	O
+the	O
+reporter	O
+gene	O
+in	O
+many	O
+different	O
+cell	O
+lines	O
+.	O
+
+We	O
+show	O
+that	O
+the	O
+5	O
+'	O
+UTR	O
+characteristic	O
+of	O
+testis	B-GENE
+-	I-GENE
+specific	I-GENE
+c	I-GENE
+-	I-GENE
+mos	I-GENE
+mRNA	I-GENE
+strongly	O
+represses	O
+translation	O
+relative	O
+to	O
+the	O
+translation	O
+of	O
+transcripts	O
+that	O
+contain	O
+a	O
+5	O
+'	O
+UTR	O
+derived	O
+from	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+mRNA	I-GENE
+,	O
+and	O
+this	O
+is	O
+mainly	O
+due	O
+to	O
+the	O
+four	O
+uORFs	O
+.	O
+
+To	O
+address	O
+the	O
+biological	O
+effect	O
+of	O
+specific	O
+isoform	O
+expression	O
+,	O
+NIH3T3	O
+cells	O
+were	O
+transfected	O
+with	O
+a	O
+eukaryotic	O
+expression	O
+vector	O
+containing	O
+cDNA	O
+for	O
+FGF8a	B-GENE
+,	O
+FGF8b	B-GENE
+,	O
+or	O
+FGF8e	B-GENE
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+the	O
+F	O
+-	O
+wave	O
+may	O
+be	O
+elicited	O
+in	O
+motoneuron	O
+of	O
+different	O
+depolarization	O
+threshold	O
+but	O
+primarily	O
+in	O
+larger	O
+and	O
+faster	O
+nerve	O
+fibers	O
+,	O
+with	O
+a	O
+lower	O
+threshold	O
+of	O
+depolarization	O
+.	O
+
+In	O
+addition	O
+,	O
+carp	B-GENE
+JAK1	I-GENE
+shows	O
+higher	O
+sequence	O
+homology	O
+to	O
+mammalian	B-GENE
+JAK1	I-GENE
+in	O
+both	O
+the	O
+kinase	O
+-	O
+like	O
+(	O
+JH2	B-GENE
+)	O
+and	O
+kinase	O
+(	O
+JH1	B-GENE
+)	O
+domains	O
+(	O
+approximately	O
+70	O
+%	O
+identity	O
+)	O
+.	O
+
+When	O
+this	O
+DNA	O
+fragment	O
+was	O
+placed	O
+upstream	O
+of	O
+the	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+reporter	O
+gene	O
+and	O
+transfected	O
+into	O
+a	O
+carp	O
+CF	O
+cell	O
+line	O
+,	O
+it	O
+could	O
+drive	O
+the	O
+synthesis	O
+of	O
+CAT	B-GENE
+enzyme	I-GENE
+16	O
+times	O
+more	O
+efficiently	O
+than	O
+the	O
+promoterless	O
+pCAT	B-GENE
+-	I-GENE
+Basic	I-GENE
+.	O
+
+Molecular	O
+cloning	O
+of	O
+Elk	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+a	O
+new	O
+member	O
+of	O
+the	O
+Ets	B-GENE
+family	I-GENE
+expressed	O
+during	O
+mouse	O
+embryogenesis	O
+and	O
+analysis	O
+of	O
+its	O
+transcriptional	O
+repression	O
+activity	O
+.	O
+
+We	O
+report	O
+an	O
+example	O
+of	O
+an	O
+MDV	O
+-	O
+transformed	O
+T	O
+-	O
+lymphoblastoid	O
+cell	O
+line	O
+(	O
+T9	O
+)	O
+expressing	O
+high	O
+levels	O
+of	O
+a	O
+truncated	B-GENE
+C	I-GENE
+-	I-GENE
+MYB	I-GENE
+protein	I-GENE
+as	O
+a	O
+result	O
+of	O
+RAV	O
+integration	O
+within	O
+one	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+allele	I-GENE
+.	O
+
+Frozen	O
+/	O
+thawed	O
+extensor	O
+digitorum	O
+longus	O
+muscle	O
+tendon	O
+units	O
+had	O
+significantly	O
+lower	O
+values	O
+for	O
+load	O
+to	O
+failure	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+energy	O
+absorbed	O
+to	O
+failure	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+strain	O
+at	O
+failure	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+they	O
+tended	O
+to	O
+fail	O
+at	O
+a	O
+different	O
+anatomic	O
+location	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+(	O
+broadly	O
+at	O
+the	O
+fascia	O
+-	O
+muscle	O
+interface	O
+as	O
+compared	O
+with	O
+horizontally	O
+at	O
+the	O
+musculotendinous	O
+junction	O
+)	O
+than	O
+fresh	O
+units	O
+.	O
+
+Northern	O
+analysis	O
+of	O
+the	O
+3	B-GENE
+.	I-GENE
+1	I-GENE
+-	I-GENE
+kb	I-GENE
+PWP2H	I-GENE
+cDNA	I-GENE
+revealed	O
+that	O
+a	O
+3	O
+.	O
+3	O
+-	O
+kb	O
+major	O
+transcript	O
+is	O
+ubiquitously	O
+expressed	O
+in	O
+human	O
+adult	O
+tissues	O
+.	O
+
+Forty	O
+-	O
+eight	O
+10	O
+-	O
+12	O
+-	O
+week	O
+-	O
+old	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+were	O
+randomized	O
+to	O
+receive	O
+,	O
+daily	O
+for	O
+28	O
+days	O
+:	O
+(	O
+1	O
+)	O
+CsA	O
+vehicle	O
+p	O
+.	O
+o	O
+.	O
+plus	O
+FB	O
+vehicle	O
+sc	O
+;	O
+(	O
+2	O
+)	O
+CsA	O
+(	O
+15	O
+mg	O
+/	O
+kg	O
+)	O
+p	O
+.	O
+o	O
+.	O
+plus	O
+FB	O
+vehicle	O
+sc	O
+,	O
+(	O
+3	O
+)	O
+CsA	O
+vehicle	O
+p	O
+.	O
+o	O
+.	O
+plus	O
+FB	O
+(	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+sc	O
+;	O
+and	O
+(	O
+4	O
+)	O
+CsA	O
+(	O
+15	O
+mg	O
+/	O
+kg	O
+)	O
+p	O
+.	O
+o	O
+.	O
+plus	O
+FB	O
+(	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+sc	O
+.	O
+
+CsA	O
+alone	O
+resulted	O
+in	O
+elevated	O
+bone	O
+turnover	O
+.	O
+
+Individuals	O
+attending	O
+the	O
+GUM	O
+Department	O
+in	O
+the	O
+Royal	O
+Infirmary	O
+of	O
+Edinburgh	O
+between	O
+1990	O
+and	O
+1994	O
+with	O
+the	O
+diagnosis	O
+of	O
+HIV	O
+infection	O
+,	O
+genital	O
+warts	O
+,	O
+genital	O
+herpes	O
+,	O
+non	O
+-	O
+specific	O
+genital	O
+infection	O
+(	O
+NSGI	O
+)	O
+,	O
+gonorrhoea	O
+and	O
+syphilis	O
+were	O
+included	O
+in	O
+the	O
+study	O
+.	O
+
+Northern	O
+blotting	O
+showed	O
+that	O
+MDMX	B-GENE
+,	O
+like	O
+MDM2	B-GENE
+,	O
+is	O
+expressed	O
+in	O
+all	O
+tissues	O
+tested	O
+,	O
+and	O
+that	O
+several	O
+mRNAs	O
+for	O
+MDMX	B-GENE
+can	O
+be	O
+detected	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+of	O
+22	O
+,	O
+846	O
+bp	O
+of	O
+the	O
+left	O
+arm	O
+of	O
+chromosome	O
+IV	O
+is	O
+described	O
+.	O
+
+Natural	O
+FL	B-GENE
+protein	I-GENE
+has	O
+been	O
+purified	O
+from	O
+a	O
+stromal	O
+cell	O
+line	O
+and	O
+shown	O
+to	O
+be	O
+a	O
+65	O
+kD	O
+nondisulfide	O
+-	O
+linked	O
+homodimeric	O
+glycoprotein	O
+comprised	O
+of	O
+30	O
+kD	O
+subunits	O
+,	O
+each	O
+containing	O
+12	O
+kD	O
+of	O
+N	O
+-	O
+and	O
+O	O
+-	O
+linked	O
+sugars	O
+.	O
+
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+examine	O
+the	O
+influence	O
+of	O
+HHCA	O
+and	O
+other	O
+serological	O
+factors	O
+upon	O
+the	O
+development	O
+of	O
+VGS	O
+.	O
+
+Spliced	O
+exons	O
+of	O
+adenovirus	O
+late	O
+RNAs	O
+colocalize	O
+with	O
+snRNP	O
+in	O
+a	O
+specific	O
+nuclear	O
+domain	O
+.	O
+
+Using	O
+Spurr	O
+'	O
+s	O
+resin	O
+as	O
+a	O
+mounting	O
+medium	O
+,	O
+we	O
+could	O
+observe	O
+thick	O
+specimens	O
+with	O
+oil	O
+immersion	O
+objective	O
+lens	O
+without	O
+the	O
+use	O
+of	O
+coverslips	O
+,	O
+then	O
+avoid	O
+air	O
+bubbles	O
+near	O
+the	O
+specimen	O
+.	O
+
+The	O
+present	O
+study	O
+investigated	O
+dose	O
+dependence	O
+and	O
+time	O
+course	O
+effects	O
+of	O
+the	O
+benzodiazepine	O
+(	O
+BDZ	O
+)	O
+partial	O
+inverse	O
+agonist	O
+,	O
+RO19	O
+-	O
+4603	O
+(	O
+0	O
+.	O
+005	O
+-	O
+0	O
+.	O
+30	O
+mg	O
+/	O
+kg	O
+)	O
+alone	O
+,	O
+and	O
+in	O
+combination	O
+with	O
+the	O
+BDZ	B-GENE
+receptor	I-GENE
+antagonists	O
+flumazenil	O
+,	O
+ZK	O
+93426	O
+,	O
+and	O
+CGS	O
+8216	O
+(	O
+20	O
+mg	O
+/	O
+kg	O
+)	O
+in	O
+selectively	O
+bred	O
+alcohol	O
+-	O
+preferring	O
+(	O
+P	O
+)	O
+rats	O
+provided	O
+a	O
+two	O
+-	O
+bottle	O
+choice	O
+test	O
+between	O
+ethanol	O
+(	O
+EtOH	O
+)	O
+(	O
+10	O
+%	O
+v	O
+/	O
+v	O
+)	O
+,	O
+and	O
+a	O
+palatable	O
+saccharin	O
+(	O
+0	O
+.	O
+0125	O
+%	O
+g	O
+/	O
+v	O
+)	O
+solution	O
+.	O
+
+Beyond	O
+the	O
+Tower	O
+of	O
+Babel	O
+:	O
+a	O
+nomenclature	O
+for	O
+suicidology	O
+.	O
+
+Infection	O
+with	O
+Neisseria	O
+meningitidis	O
+group	O
+B	O
+has	O
+been	O
+difficult	O
+to	O
+detect	O
+,	O
+partly	O
+because	O
+this	O
+bacterial	O
+group	O
+'	O
+s	O
+polysaccharide	O
+is	O
+a	O
+weak	O
+immunogen	O
+.	O
+
+Rss1p	B-GENE
+encodes	O
+a	O
+novel	O
+essential	O
+protein	O
+of	O
+538	O
+amino	O
+acids	O
+,	O
+which	O
+contains	O
+an	O
+extended	O
+predicted	O
+coiled	O
+-	O
+coil	O
+domain	O
+and	O
+is	O
+located	O
+both	O
+at	O
+nuclear	O
+pore	O
+complexes	O
+(	O
+NPCs	O
+)	O
+and	O
+in	O
+the	O
+cytoplasm	O
+.	O
+
+To	O
+map	O
+this	O
+regulatory	O
+serine	O
+phosphorylation	O
+site	O
+we	O
+developed	O
+a	O
+baculovirus	O
+-	O
+mediated	O
+expression	O
+system	O
+for	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+annexin	I-GENE
+II	I-GENE
+and	O
+for	O
+a	O
+series	O
+of	O
+annexin	B-GENE
+II	I-GENE
+mutants	I-GENE
+which	O
+contained	O
+substitutions	O
+in	O
+one	O
+or	O
+more	O
+serine	O
+residues	O
+present	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+domain	O
+.	O
+
+The	O
+PAI	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+is	O
+one	O
+of	O
+the	O
+most	O
+TNF	B-GENE
+-	I-GENE
+responsive	I-GENE
+genes	I-GENE
+known	O
+and	O
+is	O
+also	O
+highly	O
+induced	O
+by	O
+the	O
+phorbol	O
+ester	O
+phorbol	O
+12	O
+-	O
+myristate	O
+13	O
+-	O
+acetate	O
+(	O
+PMA	O
+)	O
+and	O
+the	O
+phosphatase	O
+inhibitor	O
+,	O
+okadaic	O
+acid	O
+,	O
+in	O
+both	O
+HT	O
+-	O
+1080	O
+fibrosarcoma	O
+and	O
+U	O
+-	O
+937	O
+histiocytic	O
+cells	O
+.	O
+
+220	O
+,	O
+263	O
+-	O
+273	O
+)	O
+.	O
+
+T	O
+.	O
+,	O
+Patel	O
+,	O
+S	O
+.	O
+
+Growth	O
+factors	O
+induce	O
+the	O
+expression	O
+of	O
+the	O
+immediate	B-GENE
+early	I-GENE
+gene	I-GENE
+products	I-GENE
+MAP	B-GENE
+kinase	I-GENE
+phosphatase	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+MKP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+.	O
+
+The	O
+up	O
+-	O
+regulation	O
+of	O
+E	B-GENE
+-	I-GENE
+selectin	I-GENE
+,	O
+one	O
+of	O
+the	O
+adhesion	O
+molecules	O
+on	O
+the	O
+endothelium	O
+,	O
+is	O
+an	O
+important	O
+event	O
+in	O
+the	O
+mediation	O
+of	O
+the	O
+inflammatory	O
+response	O
+.	O
+
+The	O
+NIT2	B-GENE
+protein	I-GENE
+is	O
+localised	O
+in	O
+nuclei	O
+and	O
+could	O
+not	O
+be	O
+detected	O
+in	O
+the	O
+cytoplasmic	O
+fraction	O
+of	O
+cells	O
+subjected	O
+to	O
+nitrogen	O
+derepression	O
+or	O
+nitrogen	O
+repression	O
+,	O
+indicating	O
+that	O
+the	O
+nuclear	O
+import	O
+of	O
+NIT2	B-GENE
+is	O
+not	O
+regulated	O
+.	O
+
+In	O
+spite	O
+of	O
+much	O
+effort	O
+,	O
+no	O
+one	O
+has	O
+succeeded	O
+in	O
+isolating	O
+and	O
+characterizing	O
+the	O
+enzyme	O
+(	O
+s	O
+)	O
+responsible	O
+for	O
+synthesis	O
+of	O
+cellulose	O
+,	O
+the	O
+major	O
+cell	O
+wall	O
+polymer	O
+of	O
+plants	O
+.	O
+
+Vascular	O
+responses	O
+to	O
+reactive	O
+hyperemia	O
+(	O
+with	O
+flow	O
+increase	O
+leading	O
+to	O
+endothelium	O
+-	O
+dependent	O
+dilation	O
+)	O
+and	O
+to	O
+sublingual	O
+glyceryl	O
+trinitrate	O
+(	O
+GTN	O
+;	O
+endothelium	O
+-	O
+independent	O
+dilation	O
+)	O
+were	O
+recorded	O
+.	O
+
+During	O
+this	O
+period	O
+,	O
+administration	O
+of	O
+additional	O
+exogenous	B-GENE
+PRL	I-GENE
+did	O
+not	O
+stimulate	O
+further	O
+activation	O
+(	O
+binding	O
+)	O
+of	O
+the	O
+Stat	B-GENE
+factors	I-GENE
+.	O
+
+Intraperitoneal	O
+administration	O
+of	O
+L	O
+-	O
+5	O
+-	O
+hydroxytryptophan	O
+(	O
+L	O
+-	O
+5	O
+-	O
+HTP	O
+)	O
+at	O
+doses	O
+of	O
+25	O
+to	O
+100	O
+mg	O
+/	O
+kg	O
+dramatically	O
+increase	O
+defecation	O
+in	O
+mice	O
+.	O
+
+In	O
+the	O
+VA	O
+-	O
+SMV	O
+mode	O
+,	O
+the	O
+connection	O
+was	O
+made	O
+with	O
+valved	O
+conduits	O
+from	O
+the	O
+LV	O
+apex	O
+(	O
+inflow	O
+)	O
+to	O
+the	O
+ascending	O
+aorta	O
+(	O
+outflow	O
+)	O
+(	O
+n	O
+=	O
+11	O
+)	O
+or	O
+to	O
+the	O
+DAo	O
+(	O
+n	O
+=	O
+12	O
+)	O
+.	O
+
+Factor	O
+V	O
+Leiden	O
+is	O
+a	O
+genetic	O
+disorder	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+determination	O
+of	O
+the	O
+complete	O
+secondary	O
+structure	O
+of	O
+an	O
+RNA	O
+spliced	O
+in	O
+a	O
+spliceosome	O
+.	O
+
+The	O
+majority	O
+of	O
+the	O
+cases	O
+with	O
+0	O
+-	O
+I	O
+or	O
+0	O
+-	O
+III	O
+components	O
+were	O
+sm	O
+.	O
+cancer	O
+.	O
+
+These	O
+patients	O
+appear	O
+to	O
+have	O
+slightly	O
+better	O
+pulmonary	O
+function	O
+and	O
+nutritional	O
+status	O
+;	O
+yet	O
+,	O
+they	O
+seem	O
+to	O
+have	O
+a	O
+higher	O
+degree	O
+of	O
+health	O
+care	O
+utilization	O
+.	O
+
+This	O
+observation	O
+calls	O
+for	O
+careful	O
+monitoring	O
+of	O
+calcium	O
+and	O
+alkaline	B-GENE
+phosphatase	I-GENE
+values	O
+and	O
+possible	O
+adjustments	O
+of	O
+vitamin	O
+D	O
+intake	O
+when	O
+fortifiers	O
+are	O
+used	O
+for	O
+extended	O
+periods	O
+.	O
+
+We	O
+have	O
+found	O
+that	O
+PEA2	B-GENE
+is	O
+also	O
+required	O
+for	O
+the	O
+bipolar	O
+budding	O
+pattern	O
+and	O
+that	O
+it	O
+encodes	O
+a	O
+novel	O
+protein	O
+with	O
+a	O
+predicted	O
+coiled	O
+-	O
+coil	O
+domain	O
+.	O
+
+Signaling	O
+from	O
+the	O
+small	B-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+Rac1	I-GENE
+and	O
+Cdc42	B-GENE
+to	O
+the	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+/	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+pathway	O
+.	O
+
+Percent	O
+identities	O
+of	O
+the	O
+mouse	B-GENE
+PP2	I-GENE
+to	O
+mouse	B-GENE
+Y1	I-GENE
+,	O
+mouse	O
+Y4	B-GENE
+/	O
+PP1	B-GENE
+and	O
+human	B-GENE
+Y2	I-GENE
+receptors	I-GENE
+are	O
+53	O
+,	O
+42	O
+,	O
+and	O
+31	O
+,	O
+respectively	O
+.	O
+
+Correlating	O
+with	O
+the	O
+previous	O
+observation	O
+that	O
+CBF	B-GENE
+binding	O
+to	O
+the	O
+78C1	O
+site	O
+is	O
+enhanced	O
+by	O
+EGTA	O
+and	O
+EDTA	O
+,	O
+these	O
+divalent	O
+cation	O
+chelators	O
+specifically	O
+stimulate	O
+78C1	O
+-	O
+directed	O
+transcription	O
+.	O
+
+The	O
+human	O
+gene	O
+fragment	O
+ligated	O
+to	O
+the	O
+minimal	O
+rat	O
+liver	O
+glucokinase	B-GENE
+promoter	O
+was	O
+shown	O
+to	O
+work	O
+as	O
+an	O
+enhancer	O
+in	O
+the	O
+hepatocyte	O
+transfection	O
+system	O
+.	O
+
+To	O
+test	O
+the	O
+role	O
+of	O
+ML	O
+in	O
+human	O
+reproductive	O
+axis	O
+,	O
+128	O
+healthy	O
+children	O
+,	O
+68	O
+boys	O
+and	O
+60	O
+girls	O
+,	O
+were	O
+studied	O
+.	O
+
+However	O
+,	O
+the	O
+truncated	O
+deer	B-GENE
+receptor	I-GENE
+lacks	O
+the	O
+most	O
+C	O
+-	O
+terminal	O
+tyrosine	O
+residue	O
+in	O
+the	O
+intracellular	O
+domain	O
+which	O
+is	O
+believed	O
+to	O
+be	O
+essential	O
+for	O
+activation	O
+of	O
+the	O
+beta	B-GENE
+-	I-GENE
+casein	I-GENE
+promoter	I-GENE
+.	O
+
+This	O
+report	O
+provides	O
+further	O
+evidence	O
+for	O
+the	O
+riMLF	O
+in	O
+the	O
+control	O
+of	O
+downgaze	O
+,	O
+and	O
+a	O
+synkinesis	O
+is	O
+postulated	O
+for	O
+the	O
+development	O
+of	O
+the	O
+convergence	O
+retraction	O
+nystagmus	O
+.	O
+
+Ninety	O
+-	O
+four	O
+percent	O
+of	O
+the	O
+EPs	O
+were	O
+tubal	O
+,	O
+and	O
+90	O
+%	O
+of	O
+the	O
+tubes	O
+exhibited	O
+some	O
+pathologic	O
+changes	O
+,	O
+including	O
+chronic	O
+salpingitis	O
+(	O
+49	O
+.	O
+5	O
+%	O
+)	O
+and	O
+follicular	O
+salpingitis	O
+(	O
+10	O
+%	O
+)	O
+,	O
+among	O
+others	O
+.	O
+
+The	O
+assessment	O
+using	O
+7	O
+H	O
+9	O
+liquid	O
+medium	O
+by	O
+the	O
+former	O
+author	O
+demonstrated	O
+the	O
+potent	O
+activities	O
+of	O
+both	O
+CS	O
+-	O
+940	O
+*	O
+and	O
+sparfloxacin	O
+(	O
+SPFX	O
+)	O
+,	O
+followed	O
+by	O
+AM	O
+-	O
+1155	O
+*	O
+,	O
+ciprofloxacin	O
+(	O
+CPFX	O
+)	O
+,	O
+levofloxacin	O
+(	O
+LVFX	O
+)	O
+,	O
+OPC	O
+-	O
+17116	O
+*	O
+,	O
+NM	O
+-	O
+394	O
+*	O
+in	O
+sequence	O
+.	O
+
+The	O
+STE20	B-GENE
+gene	I-GENE
+,	O
+encoding	O
+a	O
+protein	O
+kinase	O
+required	O
+for	O
+pheromone	O
+signal	O
+transduction	O
+,	O
+has	O
+recently	O
+been	O
+identified	O
+in	O
+a	O
+genetic	O
+screen	O
+for	O
+high	O
+-	O
+gene	O
+-	O
+dosage	O
+suppressors	O
+of	O
+a	O
+partly	O
+defective	O
+G	B-GENE
+beta	I-GENE
+mutation	O
+.	O
+
+This	O
+enzyme	O
+is	O
+designated	O
+(	B-GENE
+1	I-GENE
+-	I-GENE
+-	I-GENE
+>	I-GENE
+4	I-GENE
+)	I-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+xylan	I-GENE
+endohydrolase	I-GENE
+isoenzyme	I-GENE
+X	I-GENE
+-	I-GENE
+I	I-GENE
+.	O
+
+Magnetic	O
+resonance	O
+imaging	O
+in	O
+coccidioidal	O
+arthritis	O
+.	O
+
+Moloney	O
+murine	O
+leukemia	O
+virus	O
+(	O
+MMLV	O
+)	O
+-	O
+derived	O
+pUCMoTiN	O
+-	O
+based	O
+retroviral	O
+vectors	O
+were	O
+engineered	O
+to	O
+allow	O
+constitutive	O
+and	O
+Tat	B-GENE
+(	O
+trans	B-GENE
+-	I-GENE
+activator	I-GENE
+of	I-GENE
+transcription	I-GENE
+)	O
+-	O
+inducible	O
+expression	O
+of	O
+five	O
+hammerhead	O
+ribozymes	O
+targeted	O
+against	O
+highly	O
+conserved	O
+sequences	O
+within	O
+the	O
+group	B-GENE
+antigen	I-GENE
+(	O
+Gag	B-GENE
+)	O
+,	O
+protease	B-GENE
+(	O
+Pro	B-GENE
+)	O
+,	O
+reverse	B-GENE
+transcriptase	I-GENE
+(	O
+RT	B-GENE
+)	O
+,	O
+tat	B-GENE
+,	O
+and	O
+envelope	B-GENE
+(	O
+Env	B-GENE
+)	O
+coding	O
+regions	O
+of	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+-	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+RNA	O
+.	O
+
+REM	O
+sleep	O
+deprivation	O
+was	O
+performed	O
+using	O
+the	O
+platform	O
+technique	O
+.	O
+
+The	O
+same	O
+ligands	O
+also	O
+exhibit	O
+a	O
+similar	O
+inhibitory	O
+effect	O
+on	O
+PDGF	B-GENE
+-	I-GENE
+BB	I-GENE
+-	O
+dependent	O
+[	O
+3H	O
+]	O
+thymidine	O
+incorporation	O
+in	O
+PAE	O
+cells	O
+expressing	O
+the	O
+PDGF	B-GENE
+beta	I-GENE
+-	I-GENE
+receptors	I-GENE
+.	O
+
+We	O
+analyzed	O
+serial	O
+biopsy	O
+specimens	O
+from	O
+eight	O
+patients	O
+with	O
+FL	O
+for	O
+secondary	O
+alterations	O
+of	O
+the	O
+rearranged	B-GENE
+bcl	I-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+in	O
+the	O
+breakpoint	O
+and	O
+open	O
+reading	O
+frame	O
+(	O
+ORF	O
+)	O
+regions	O
+.	O
+
+In	O
+all	O
+eight	O
+cases	O
+,	O
+neither	O
+FL	O
+nor	O
+DLL	O
+cells	O
+showed	O
+alterations	O
+of	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+sequences	I-GENE
+in	O
+the	O
+breakpoint	O
+region	O
+,	O
+suggesting	O
+high	O
+conservation	O
+of	O
+the	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+during	O
+both	O
+t	O
+(	O
+14	O
+;	O
+18	O
+)	O
+translocation	O
+and	O
+morphologic	O
+transformation	O
+of	O
+the	O
+FL	O
+cells	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+Bazett	O
+-	O
+corrected	O
+QT	O
+(	O
+QTc	O
+)	O
+interval	O
+during	O
+exercise	O
+has	O
+been	O
+used	O
+as	O
+a	O
+marker	O
+for	O
+ischemic	O
+disease	O
+,	O
+arrhythmogenic	O
+substrate	O
+and	O
+the	O
+long	O
+QT	O
+syndrome	O
+.	O
+
+An	O
+essential	O
+role	O
+of	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+in	O
+basal	O
+and	O
+PMA	O
+-	O
+stimulated	O
+transcription	O
+of	O
+the	O
+PAI	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+is	O
+demonstrated	O
+by	O
+our	O
+finding	O
+that	O
+antisense	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+oligodeoxynucleotides	O
+both	O
+strongly	O
+reduced	O
+basal	O
+and	O
+PMA	O
+-	O
+stimulated	O
+PAI	B-GENE
+-	I-GENE
+1	I-GENE
+synthesis	O
+.	O
+
+To	O
+analyze	O
+the	O
+mechanism	O
+of	O
+fos	B-GENE
+/	O
+jun	B-GENE
+activation	O
+by	O
+TCDD	O
+we	O
+have	O
+used	O
+electrophoretic	O
+mobility	O
+shift	O
+and	O
+transient	O
+expression	O
+assays	O
+of	O
+reporter	O
+gene	O
+constructs	O
+containing	O
+response	O
+elements	O
+for	O
+12	O
+-	O
+O	O
+-	O
+tetradecanoyl	O
+-	O
+phorbol	O
+-	O
+13	O
+-	O
+acetate	O
+(	O
+TRE	O
+)	O
+,	O
+serum	O
+(	O
+SRE	O
+)	O
+,	O
+cAMP	O
+(	O
+CRE	O
+)	O
+,	O
+and	O
+aromatic	O
+hydrocarbons	O
+(	O
+AhRE	O
+)	O
+from	O
+the	O
+fos	B-GENE
+and	O
+jun	B-GENE
+genes	I-GENE
+fused	O
+to	O
+the	O
+firefly	B-GENE
+luciferase	I-GENE
+gene	I-GENE
+under	O
+the	O
+control	O
+of	O
+the	O
+SV40	B-GENE
+minimal	I-GENE
+promoter	I-GENE
+.	O
+
+The	O
+optimal	O
+sequence	O
+for	O
+interaction	O
+with	O
+mu	B-GENE
+2	I-GENE
+and	O
+with	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+has	O
+tyrosine	O
+as	O
+an	O
+anchor	O
+and	O
+prefers	O
+arginine	O
+at	O
+position	O
+Y	O
++	O
+2	O
+and	O
+leucine	O
+at	O
+position	O
+Y	O
++	O
+3	O
+.	O
+
+STK	B-GENE
+/	O
+RON	B-GENE
+-	O
+expressing	O
+Ba	O
+/	O
+F3	O
+pro	O
+-	O
+B	O
+cells	O
+(	O
+BaF	O
+/	O
+STK	B-GENE
+)	O
+exhibited	O
+MSP	B-GENE
+-	O
+dependent	O
+growth	O
+,	O
+whereas	O
+STK	B-GENE
+/	O
+RON	B-GENE
+-	O
+expressing	O
+mouse	O
+erythroleukaemia	O
+cells	O
+(	O
+MEL	O
+/	O
+STK	B-GENE
+)	O
+displayed	O
+MSP	B-GENE
+-	O
+induced	O
+apoptosis	O
+.	O
+
+In	O
+vitro	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+showed	O
+that	O
+OxyR	B-GENE
+-	I-GENE
+C199S	I-GENE
+protected	O
+Pmom	B-GENE
+from	O
+-	O
+104	O
+to	O
+-	O
+46	O
+on	O
+the	O
+top	O
+strand	O
+and	O
+produced	O
+a	O
+protection	O
+pattern	O
+characteristic	O
+of	O
+reduced	B-GENE
+wild	I-GENE
+-	I-GENE
+type	I-GENE
+OxyR	I-GENE
+.	O
+
+Kss1	B-GENE
+binds	O
+specifically	O
+to	O
+a	O
+GST	B-GENE
+-	O
+Dig1	B-GENE
+fusion	O
+in	O
+the	O
+absence	O
+of	O
+any	O
+other	O
+yeast	O
+protein	O
+.	O
+
+In	O
+contrast	O
+,	O
+dig1	B-GENE
+dig2	B-GENE
+cells	O
+constitutively	O
+invade	O
+agar	O
+medium	O
+,	O
+whereas	O
+a	O
+dig1	B-GENE
+dig2	B-GENE
+ste12	B-GENE
+triple	O
+mutant	O
+does	O
+not	O
+,	O
+indicating	O
+that	O
+Dig1	B-GENE
+and	O
+Dig2	B-GENE
+share	O
+a	O
+role	O
+in	O
+negatively	O
+regulating	O
+the	O
+invasive	O
+growth	O
+pathway	O
+.	O
+
+Comparison	O
+of	O
+the	O
+sequences	O
+of	O
+the	O
+xFxFG	O
+repeat	O
+regions	O
+of	O
+p62	B-GENE
+and	O
+Nsplp	B-GENE
+indicated	O
+that	O
+NTF2	B-GENE
+was	O
+probably	O
+interacting	O
+with	O
+the	O
+phenylalanine	O
+-	O
+containing	O
+core	O
+of	O
+these	O
+repeats	O
+and	O
+not	O
+the	O
+intervening	O
+hydrophilic	O
+linkers	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+report	O
+of	O
+the	O
+successful	O
+resection	O
+of	O
+a	O
+MFH	O
+originating	O
+in	O
+the	O
+renal	O
+capsular	O
+tissue	O
+and	O
+extending	O
+into	O
+the	O
+inferior	O
+vena	O
+cava	O
+.	O
+
+Transient	O
+expression	O
+of	O
+VSF	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+protoplasts	O
+stimulated	O
+vs	B-GENE
+-	I-GENE
+1	I-GENE
+dependent	O
+activation	O
+of	O
+the	O
+-	B-GENE
+76	I-GENE
+/	I-GENE
+grp1	I-GENE
+.	I-GENE
+8	I-GENE
+minimal	I-GENE
+promoter	I-GENE
+.	O
+
+Keeping	O
+in	O
+mind	O
+the	O
+limited	O
+range	O
+of	O
+age	O
+and	O
+dosages	O
+,	O
+advantages	O
+and	O
+disadvantages	O
+of	O
+the	O
+drug	O
+are	O
+discussed	O
+,	O
+comparing	O
+the	O
+experimental	O
+results	O
+with	O
+those	O
+derived	O
+from	O
+the	O
+literature	O
+.	O
+
+Blood	O
+sampling	O
+procedures	O
+were	O
+videotaped	O
+.	O
+
+Analysis	O
+of	O
+one	O
+cDNA	O
+revealed	O
+an	O
+unusual	O
+splicing	O
+event	O
+involving	O
+EZH1	B-GENE
+and	O
+a	O
+tandemly	O
+linked	O
+gene	O
+GPR2	B-GENE
+and	O
+suggests	O
+a	O
+potential	O
+mechanism	O
+for	O
+modifying	O
+the	O
+EZH1	B-GENE
+protein	I-GENE
+in	O
+the	O
+conserved	O
+C	O
+-	O
+terminal	O
+domain	O
+.	O
+
+A	O
+given	O
+standard	O
+input	O
+function	O
+and	O
+a	O
+given	O
+value	O
+of	O
+distribution	O
+volume	O
+(	O
+Vd	O
+)	O
+used	O
+for	O
+the	O
+rCBF	O
+measurement	O
+of	O
+this	O
+method	O
+were	O
+calculated	O
+from	O
+the	O
+dynamic	O
+study	O
+by	O
+six	O
+normal	O
+volunteers	O
+.	O
+
+They	O
+lack	O
+a	O
+predicted	O
+single	O
+stranded	O
+(	O
+ss	O
+)	O
+DNA	O
+binding	O
+motif	O
+that	O
+is	O
+unique	O
+the	O
+large	O
+terminase	B-GENE
+proteins	I-GENE
+in	O
+T4	B-GENE
+gp17	I-GENE
+,	O
+and	O
+that	O
+has	O
+been	O
+implicated	O
+in	O
+recognizing	O
+ssDNA	O
+regions	O
+in	O
+replicating	O
+and	O
+recombining	O
+T4DNA	O
+destined	O
+to	O
+be	O
+packaged	O
+.	O
+
+It	O
+can	O
+be	O
+concluded	O
+that	O
+in	O
+normotensive	O
+subjects	O
+,	O
+uric	O
+acid	O
+and	O
+xanthine	B-GENE
+oxidase	I-GENE
+have	O
+significant	O
+association	O
+with	O
+blood	O
+pressure	O
+and	O
+thus	O
+are	O
+one	O
+of	O
+the	O
+many	O
+factors	O
+which	O
+are	O
+involved	O
+in	O
+the	O
+cause	O
+or	O
+effect	O
+of	O
+hypertension	O
+.	O
+
+Immunoblotting	O
+of	O
+expressed	O
+recombinant	O
+proteins	O
+with	O
+the	O
+monoclonal	B-GENE
+08L	I-GENE
+antibody	I-GENE
+localized	O
+the	O
+08L	B-GENE
+epitope	O
+to	O
+the	O
+carboxyl	O
+end	O
+of	O
+the	O
+protein	O
+.	O
+
+We	O
+infer	O
+that	O
+the	O
+dominant	O
+negative	O
+inhibition	O
+results	O
+from	O
+both	O
+direct	O
+proteolysis	O
+of	O
+the	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+tetramer	I-GENE
+by	O
+the	O
+fusion	O
+subunit	O
+and	O
+detour	O
+of	O
+the	O
+tetramer	O
+to	O
+the	O
+lysosome	O
+.	O
+
+The	O
+current	O
+study	O
+defines	O
+the	O
+vinculin	B-GENE
+-	O
+and	O
+FAK	B-GENE
+-	I-GENE
+interaction	I-GENE
+domains	I-GENE
+on	O
+paxillin	B-GENE
+and	O
+identifies	O
+the	O
+principal	O
+paxillin	B-GENE
+focal	O
+adhesion	O
+targeting	O
+motif	O
+.	O
+
+These	O
+data	O
+demonstrate	O
+the	O
+presence	O
+of	O
+a	O
+single	O
+binding	O
+site	O
+for	O
+vinculin	B-GENE
+,	O
+and	O
+at	O
+least	O
+two	O
+binding	O
+sites	O
+for	O
+FAK	B-GENE
+that	O
+are	O
+separated	O
+by	O
+an	O
+intervening	O
+stretch	O
+of	O
+100	O
+amino	O
+acids	O
+.	O
+
+These	O
+data	O
+demonstrate	O
+that	O
+paxillin	B-GENE
+localizes	O
+to	O
+focal	O
+adhesions	O
+independent	O
+of	O
+interactions	O
+with	O
+vinculin	B-GENE
+and	O
+/	O
+or	O
+FAK	B-GENE
+,	O
+and	O
+represents	O
+the	O
+first	O
+definitive	O
+demonstration	O
+of	O
+LIM	B-GENE
+domains	I-GENE
+functioning	O
+as	O
+a	O
+primary	O
+determinant	O
+of	O
+protein	O
+subcellular	O
+localization	O
+to	O
+focal	O
+adhesions	O
+.	O
+
+A	O
+single	O
+protease	O
+-	O
+resistant	O
+structure	O
+formed	O
+by	O
+the	O
+entirety	O
+of	O
+both	O
+PDZ	B-GENE
+repeats	I-GENE
+1	I-GENE
+and	I-GENE
+2	I-GENE
+(	O
+PDZ1	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+contains	O
+the	O
+protein	B-GENE
+4	I-GENE
+.	I-GENE
+1	I-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+.	O
+
+Several	O
+agents	O
+have	O
+been	O
+tried	O
+for	O
+treatment	O
+,	O
+often	O
+limited	O
+by	O
+toxic	O
+side	O
+effects	O
+.	O
+
+Jerseys	O
+had	O
+higher	O
+hepatic	O
+Cu	O
+concentrations	O
+than	O
+did	O
+Holsteins	O
+on	O
+d	O
+60	O
+(	O
+346	O
+vs	O
+.	O
+
+These	O
+results	O
+are	O
+consistent	O
+with	O
+the	O
+well	O
+established	O
+polarity	O
+of	O
+RXR	B-GENE
+heterodimer	O
+binding	O
+to	O
+bipartite	O
+hormone	O
+response	O
+elements	O
+,	O
+with	O
+the	O
+VDR	B-GENE
+recognizing	O
+the	O
+3	O
+'	O
+-	O
+half	O
+-	O
+element	O
+.	O
+
+PPAR	B-GENE
+gamma	I-GENE
+mRNA	I-GENE
+levels	O
+were	O
+reduced	O
+by	O
+95	O
+%	O
+with	O
+3	O
+nM	O
+TNF	B-GENE
+alpha	I-GENE
+treatment	O
+for	O
+24	O
+h	O
+.	O
+
+Exons	O
+III	O
+to	O
+VIII	O
+,	O
+which	O
+cover	O
+the	O
+coding	O
+region	O
+and	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+,	O
+are	O
+almost	O
+identical	O
+in	O
+all	O
+types	O
+of	O
+PST	B-GENE
+or	O
+AST	B-GENE
+cDNAs	I-GENE
+.	O
+
+Growth	O
+factor	O
+allows	O
+effective	O
+dose	O
+-	O
+intensive	O
+regimen	O
+in	O
+advanced	O
+breast	O
+cancer	O
+patients	O
+.	O
+
+Recombinant	B-GENE
+erythropoietin	I-GENE
+(	O
+r	B-GENE
+-	I-GENE
+HuEPO	I-GENE
+)	O
+in	O
+the	O
+treatment	O
+of	O
+anemia	O
+in	O
+multiple	O
+myeloma	O
+
+In	O
+1993	O
+and	O
+1994	O
+and	O
+infection	O
+with	O
+body	O
+lice	O
+was	O
+registered	O
+41	O
+times	O
+in	O
+31	O
+patients	O
+at	O
+the	O
+clinic	O
+for	O
+homeless	O
+of	O
+the	O
+Community	O
+Health	O
+Service	O
+of	O
+Utrecht	O
+.	O
+
+Ki	B-GENE
+-	I-GENE
+ras	I-GENE
+and	O
+p53	B-GENE
+mutations	I-GENE
+in	O
+pancreatic	O
+ductal	O
+adenocarcinoma	O
+.	O
+
+Epidemiological	O
+data	O
+are	O
+quite	O
+controversial	O
+but	O
+sudden	O
+death	O
+occurring	O
+during	O
+sporting	O
+activity	O
+is	O
+probably	O
+not	O
+a	O
+rare	O
+occurrence	O
+.	O
+
+However	O
+,	O
+the	O
+ratio	O
+M	O
+/	O
+Pc	O
+provides	O
+a	O
+useful	O
+index	O
+that	O
+seems	O
+to	O
+be	O
+independent	O
+of	O
+the	O
+metabolic	O
+demand	O
+.	O
+
+Rat	B-GENE
+liver	I-GENE
+catalase	I-GENE
+is	O
+sorted	O
+to	O
+peroxisomes	O
+by	O
+its	O
+C	O
+-	O
+terminal	O
+tripeptide	O
+Ala	O
+-	O
+Asn	O
+-	O
+Leu	O
+,	O
+not	O
+by	O
+the	O
+internal	O
+Ser	O
+-	O
+Lys	O
+-	O
+Leu	O
+motif	O
+.	O
+
+These	O
+data	O
+provide	O
+strong	O
+evidence	O
+that	O
+E2F	B-GENE
+or	O
+an	O
+E2F	B-GENE
+-	I-GENE
+related	I-GENE
+transcription	I-GENE
+factor	I-GENE
+is	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+nonmuscle	B-GENE
+myosin	I-GENE
+expression	O
+.	O
+
+When	O
+the	O
+E1A	B-GENE
+N	I-GENE
+-	I-GENE
+terminus	I-GENE
+is	O
+used	O
+as	O
+a	O
+competitor	O
+in	O
+squelshing	O
+experiments	O
+it	O
+abolishes	O
+CBP	B-GENE
+-	O
+induced	O
+activation	O
+of	O
+E2F1	B-GENE
+/	O
+DP1	B-GENE
+,	O
+whereas	O
+an	O
+E1A	B-GENE
+mutant	I-GENE
+lacking	O
+CBP	B-GENE
+binding	O
+ability	O
+fails	O
+to	O
+do	O
+so	O
+.	O
+
+Small	O
+Maf	B-GENE
+proteins	I-GENE
+interact	O
+with	O
+the	O
+human	O
+transcription	O
+factor	O
+TCF11	B-GENE
+/	O
+Nrf1	B-GENE
+/	O
+LCR	B-GENE
+-	I-GENE
+F1	I-GENE
+.	O
+
+On	O
+the	O
+third	O
+occasion	O
+water	O
+(	O
+W	O
+)	O
+was	O
+ingested	O
+throughout	O
+the	O
+run	O
+.	O
+
+The	O
+effect	O
+of	O
+maternal	O
+ingestion	O
+of	O
+the	O
+reduced	O
+energy	O
+sweetener	O
+erythritol	O
+was	O
+investigated	O
+in	O
+KBL	O
+:	O
+JW	O
+strain	O
+pregnant	O
+rabbits	O
+.	O
+
+The	O
+nm23	B-GENE
+-	I-GENE
+H1	I-GENE
+/	O
+nm23	B-GENE
+-	I-GENE
+H2	I-GENE
+gene	O
+transcriptional	O
+activity	O
+ratio	O
+varied	O
+depending	O
+on	O
+the	O
+cell	O
+line	O
+.	O
+
+CONCLUSION	O
+:	O
+Intravenous	O
+diazepam	O
+administration	O
+before	O
+EGD	O
+produces	O
+a	O
+significant	O
+fall	O
+in	O
+SpO2	O
+during	O
+the	O
+procedure	O
+,	O
+and	O
+so	O
+should	O
+be	O
+avoided	O
+;	O
+continuous	O
+monitoring	O
+of	O
+SpO2	O
+should	O
+be	O
+done	O
+during	O
+EGD	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+alignment	O
+between	O
+mouse	O
+and	O
+human	B-GENE
+CA	I-GENE
+IV	I-GENE
+shows	O
+69	O
+%	O
+identity	O
+in	O
+the	O
+coding	O
+region	O
+and	O
+all	O
+of	O
+the	O
+exon	O
+-	O
+intron	O
+boundaries	O
+are	O
+conserved	O
+,	O
+as	O
+are	O
+the	O
+sizes	O
+of	O
+the	O
+introns	O
+.	O
+
+Discordance	O
+on	O
+the	O
+cost	O
+dimension	O
+correlated	O
+negatively	O
+with	O
+G	B-GENE
+Hb	I-GENE
+,	O
+suggesting	O
+better	O
+glycemic	O
+control	O
+with	O
+greater	O
+disagreement	O
+.	O
+
+DATA	O
+SOURCES	O
+:	O
+Epidemiologic	O
+studies	O
+,	O
+research	O
+studies	O
+,	O
+review	O
+articles	O
+,	O
+and	O
+government	O
+reports	O
+pertaining	O
+to	O
+epidemiology	O
+of	O
+lung	O
+cancer	O
+.	O
+
+Histological	O
+changes	O
+,	O
+including	O
+cortical	O
+cell	O
+involution	O
+and	O
+hemorrhage	O
+occurring	O
+during	O
+the	O
+neonatal	O
+period	O
+,	O
+would	O
+seem	O
+to	O
+have	O
+crucial	O
+relevance	O
+to	O
+the	O
+remodeling	O
+of	O
+the	O
+adrenal	O
+vasculature	O
+.	O
+
+Furthermore	O
+,	O
+co	O
+-	O
+expression	O
+of	O
+both	O
+p46	B-GENE
+and	O
+p54	B-GENE
+subunits	I-GENE
+markedly	O
+altered	O
+the	O
+subcellular	O
+distribution	O
+of	O
+p46	B-GENE
+;	O
+co	O
+-	O
+expressed	O
+p46	B-GENE
+was	O
+transported	O
+into	O
+the	O
+nucleus	O
+as	O
+efficiently	O
+as	O
+p54	B-GENE
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+,	O
+although	O
+both	O
+the	O
+N	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+regions	O
+of	O
+talin	B-GENE
+bind	O
+actin	B-GENE
+,	O
+the	O
+properties	O
+of	O
+these	O
+two	O
+regions	O
+of	O
+the	O
+protein	O
+are	O
+distinct	O
+.	O
+
+Merr	O
+.	O
+)	O
+embryo	O
+library	O
+.	O
+
+The	O
+accumulation	O
+of	O
+both	O
+LHA4	B-GENE
+and	O
+LHA2	B-GENE
+mRNAs	I-GENE
+is	O
+induced	O
+by	O
+the	O
+addition	O
+of	O
+exogenous	O
+sugars	O
+and	O
+this	O
+induction	O
+appears	O
+to	O
+be	O
+dependent	O
+on	O
+sugar	O
+uptake	O
+and	O
+metabolism	O
+,	O
+because	O
+mannitol	O
+and	O
+3	O
+-	O
+O	O
+-	O
+methylglucose	O
+do	O
+not	O
+stimulate	O
+mRNA	O
+accumulation	O
+.	O
+
+Using	O
+the	O
+yeast	O
+one	O
+-	O
+hybrid	O
+screen	O
+with	O
+integrated	O
+NRE	O
+and	O
+flanking	O
+DNA	O
+as	O
+bait	O
+,	O
+the	O
+predominant	O
+clone	O
+obtained	O
+was	O
+bovine	B-GENE
+Nrl	I-GENE
+.	O
+
+As	O
+the	O
+rate	O
+of	O
+protein	O
+synthesis	O
+decreases	O
+during	O
+late	O
+embryogenesis	O
+,	O
+levels	O
+of	O
+SEC	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+its	O
+cognate	O
+mRNA	O
+decline	O
+precipitously	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+fodrin	B-GENE
+proteolysis	O
+in	O
+vivo	O
+may	O
+reflect	O
+the	O
+activity	O
+of	O
+multiple	O
+ICE	B-GENE
+/	O
+Ced	B-GENE
+-	I-GENE
+3	I-GENE
+proteases	O
+whose	O
+partial	O
+sensitivity	O
+to	O
+DEVD	O
+-	O
+CHO	O
+reflects	O
+a	O
+limited	O
+contribution	O
+from	O
+CPP32	B-GENE
+,	O
+or	O
+an	O
+ICE	B-GENE
+/	O
+Ced	B-GENE
+-	I-GENE
+3	I-GENE
+protease	O
+less	O
+sensitive	O
+than	O
+CPP32	B-GENE
+to	O
+DEVD	O
+-	O
+CHO	O
+inhibition	O
+.	O
+
+In	O
+3Y1	O
+and	O
+3Y1	O
+v	B-GENE
+-	I-GENE
+crk	I-GENE
+-	O
+transformed	O
+fibroblasts	O
+,	O
+almost	O
+all	O
+of	O
+the	O
+total	O
+PTP1B	B-GENE
+and	O
+about	O
+40	O
+%	O
+of	O
+total	O
+p130	B-GENE
+(	O
+Cas	B-GENE
+)	O
+co	O
+-	O
+sediment	O
+with	O
+membranes	O
+composed	O
+primarily	O
+of	O
+endoplasmic	O
+reticulum	O
+.	O
+
+Replacing	O
+residues	O
+405	O
+-	O
+419	O
+on	O
+delta419	O
+with	O
+the	O
+conserved	O
+AF	O
+-	O
+2	O
+domain	O
+from	O
+the	O
+vitamin	B-GENE
+D3	I-GENE
+receptor	I-GENE
+or	O
+the	O
+estrogen	B-GENE
+receptor	I-GENE
+results	O
+in	O
+a	O
+receptor	O
+with	O
+wild	O
+-	O
+type	O
+or	O
+low	O
+transcriptional	O
+activity	O
+,	O
+respectively	O
+.	O
+
+Recurrent	O
+G	O
+-	O
+to	O
+-	O
+A	O
+substitution	O
+in	O
+a	O
+single	O
+codon	O
+of	O
+SREBP	B-GENE
+cleavage	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+causes	O
+sterol	O
+resistance	O
+in	O
+three	O
+mutant	O
+Chinese	O
+hamster	O
+ovary	O
+cell	O
+lines	O
+.	O
+
+The	O
+Escherichia	B-GENE
+coli	I-GENE
+tet	I-GENE
+-	I-GENE
+repressor	I-GENE
+(	O
+TetR	B-GENE
+)	O
+operator	O
+system	O
+was	O
+used	O
+to	O
+develop	O
+a	O
+variation	O
+of	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+assay	O
+in	O
+which	O
+disruptions	O
+of	O
+protein	O
+-	O
+protein	O
+interactions	O
+can	O
+be	O
+identified	O
+by	O
+a	O
+positive	O
+selection	O
+.	O
+
+Recent	O
+studies	O
+have	O
+suggested	O
+that	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+regulates	O
+the	O
+function	O
+of	O
+Jak	B-GENE
+family	O
+tyrosine	B-GENE
+kinases	I-GENE
+,	O
+as	O
+shown	O
+by	O
+its	O
+constitutive	O
+association	O
+with	O
+the	O
+Tyk2	B-GENE
+kinase	I-GENE
+and	O
+the	O
+hyperphosphorylation	O
+of	O
+Jak	B-GENE
+kinases	I-GENE
+in	O
+the	O
+motheaten	O
+cells	O
+that	O
+lack	O
+functional	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Administration	O
+of	O
+a	O
+second	O
+dose	O
+of	O
+vaccine	O
+during	O
+the	O
+outbreak	O
+was	O
+not	O
+protective	O
+.	O
+
+But	O
+,	O
+as	O
+Theriault	O
+explains	O
+,	O
+improvements	O
+in	O
+assessing	O
+exposure	O
+have	O
+not	O
+yet	O
+translated	O
+into	O
+clear	O
+and	O
+consistent	O
+findings	O
+.	O
+
+Biol	O
+.	O
+
+Structural	O
+basis	O
+for	O
+activation	O
+of	O
+human	B-GENE
+lymphocyte	I-GENE
+kinase	I-GENE
+Lck	B-GENE
+upon	O
+tyrosine	O
+phosphorylation	O
+.	O
+
+Evolutive	O
+morphology	O
+of	O
+the	O
+olfactory	O
+bulb	O
+in	O
+man	O
+and	O
+certain	O
+non	O
+-	O
+human	O
+mammals	O
+
+From	O
+these	O
+results	O
+,	O
+we	O
+concluded	O
+that	O
+this	O
+ORF	O
+is	O
+the	O
+FRDS	B-GENE
+gene	I-GENE
+.	O
+
+FK506	O
+is	O
+10	O
+-	O
+to	O
+100	O
+-	O
+fold	O
+more	O
+potent	O
+than	O
+cyclosporin	O
+A	O
+in	O
+preventing	O
+organ	O
+rejection	O
+and	O
+in	O
+toxicity	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+Rho1p	B-GENE
+regulates	O
+cytoskeletal	O
+reorganization	O
+at	O
+least	O
+through	O
+Bni1p	B-GENE
+and	O
+Pkc1p	B-GENE
+.	O
+
+Waves	O
+N1	O
+,	O
+P3	O
+and	O
+CNV	O
+were	O
+recorded	O
+during	O
+a	O
+CNV	O
+paradigm	O
+in	O
+a	O
+simple	O
+reaction	O
+time	O
+task	O
+with	O
+a	O
+constant	O
+interstimulus	O
+interval	O
+(	O
+ISI	O
+)	O
+of	O
+1	O
+sec	O
+.	O
+
+Therefore	O
+,	O
+both	O
+the	O
+Chilean	O
+and	O
+the	O
+Japanese	O
+samples	O
+collected	O
+in	O
+high	O
+-	O
+risk	O
+areas	O
+showed	O
+higher	O
+mutagenic	O
+rates	O
+than	O
+the	O
+Japanese	O
+ones	O
+in	O
+a	O
+low	O
+-	O
+risk	O
+area	O
+,	O
+with	O
+a	O
+statistical	O
+significance	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+chi	O
+-	O
+square	O
+test	O
+)	O
+.	O
+
+Regulation	O
+of	O
+ASN1	B-GENE
+and	O
+ASN2	B-GENE
+expression	O
+was	O
+studied	O
+using	O
+lacZ	B-GENE
+fusions	I-GENE
+and	O
+both	O
+genes	O
+were	O
+found	O
+to	O
+be	O
+several	O
+times	O
+less	O
+expressed	O
+in	O
+the	O
+absence	O
+of	O
+the	O
+transcription	O
+activator	O
+Gcn4p	B-GENE
+.	O
+
+Several	O
+particular	O
+features	O
+of	O
+this	O
+polypeptide	O
+fragment	O
+from	O
+the	O
+hamster	B-GENE
+lysyl	I-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+suggest	O
+that	O
+it	O
+is	O
+implicated	O
+in	O
+the	O
+assembly	O
+of	O
+that	O
+enzyme	O
+within	O
+the	O
+multisynthetase	O
+complex	O
+.	O
+
+He	O
+is	O
+well	O
+,	O
+five	O
+years	O
+after	O
+relapse	O
+.	O
+
+Comparison	O
+of	O
+the	O
+proportion	O
+of	O
+nonsynonymous	O
+(	O
+pN	O
+)	O
+and	O
+synonymous	O
+(	O
+pS	O
+)	O
+substitutions	O
+occurring	O
+per	O
+site	O
+within	O
+tamarin	B-GENE
+variable	I-GENE
+region	I-GENE
+genes	I-GENE
+demonstrated	O
+a	O
+reduction	O
+in	O
+pN	O
+in	O
+the	O
+framework	O
+regions	O
+compared	O
+with	O
+pN	O
+in	O
+the	O
+presumed	O
+MHC	B-GENE
+contact	I-GENE
+regions	I-GENE
+(	O
+CDR1	B-GENE
+and	O
+CDR2	B-GENE
+)	O
+.	O
+
+The	O
+effects	O
+of	O
+oral	O
+vanadyl	O
+sulfate	O
+(	O
+VOSO4	O
+)	O
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+)	O
+on	O
+anthropometry	O
+,	O
+body	O
+composition	O
+,	O
+and	O
+performance	O
+were	O
+investigated	O
+in	O
+a	O
+12	O
+-	O
+week	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+trial	O
+involving	O
+weight	O
+-	O
+training	O
+volunteers	O
+.	O
+
+Later	O
+in	O
+development	O
+,	O
+Tbx6	B-GENE
+expression	O
+is	O
+restricted	O
+to	O
+presomitic	O
+,	O
+paraxial	O
+mesoderm	O
+and	O
+to	O
+the	O
+tail	O
+bud	O
+,	O
+which	O
+replaces	O
+the	O
+streak	O
+as	O
+the	O
+source	O
+of	O
+mesoderm	O
+.	O
+
+Disruption	O
+of	O
+re	O
+-	O
+replication	O
+control	O
+by	O
+overexpression	O
+of	O
+human	B-GENE
+ORC1	I-GENE
+in	O
+fission	O
+yeast	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+that	O
+the	O
+promoter	O
+and	O
+enhancer	O
+regions	O
+identified	O
+here	O
+are	O
+essential	O
+for	O
+maintaining	O
+the	O
+efficient	O
+promoter	O
+activity	O
+of	O
+the	O
+human	B-GENE
+activin	I-GENE
+betaA	I-GENE
+subunit	I-GENE
+gene	I-GENE
+.	O
+
+Recombinant	O
+,	O
+bacterially	O
+expressed	O
+PIP5KIalpha	B-GENE
+possessed	O
+PIP5K	B-GENE
+activity	O
+and	O
+was	O
+immunoreactive	O
+with	O
+erythroid	B-GENE
+PIP5KI	I-GENE
+antibodies	I-GENE
+.	O
+
+Human	B-GENE
+acid	I-GENE
+ceramidase	I-GENE
+(	O
+(	B-GENE
+AC	I-GENE
+)	I-GENE
+N	I-GENE
+-	I-GENE
+acylsphingosine	I-GENE
+amidohydrolase	I-GENE
+,	O
+EC	B-GENE
+3	I-GENE
+.	I-GENE
+5	I-GENE
+.	O
+
+The	O
+0	O
+.	O
+22	O
+-	O
+kb	O
+NheI	B-GENE
+/	O
+BglII	B-GENE
+promoter	O
+exhibited	O
+PMA	O
+inducibility	O
+in	O
+myeloid	O
+cells	O
+and	O
+contained	O
+a	O
+PMA	O
+-	O
+responsive	O
+element	O
+recognized	O
+by	O
+Sp1	B-GENE
+and	O
+EGR	B-GENE
+-	I-GENE
+1	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+Northern	O
+(	O
+RNA	O
+)	O
+blot	O
+analyses	O
+indicated	O
+that	O
+the	O
+cdh	B-GENE
+genes	I-GENE
+encoding	O
+the	O
+five	O
+subunits	O
+and	O
+an	O
+open	O
+reading	O
+frame	O
+(	O
+ORF1	O
+)	O
+with	O
+unknown	O
+function	O
+are	O
+cotranscribed	O
+during	O
+growth	O
+on	O
+acetate	O
+.	O
+
+Two	O
+classes	O
+of	O
+mutations	O
+were	O
+obtained	O
+:	O
+(	O
+i	O
+)	O
+those	O
+that	O
+altered	O
+the	O
+coding	O
+region	O
+of	O
+HOL1	B-GENE
+,	O
+conferring	O
+the	O
+ability	O
+to	O
+take	O
+up	O
+histidinol	O
+;	O
+and	O
+(	O
+ii	O
+)	O
+cis	O
+-	O
+acting	O
+mutations	O
+(	O
+selected	O
+in	O
+a	O
+mutant	O
+HOL1	B-GENE
+-	I-GENE
+1	I-GENE
+background	O
+)	O
+that	O
+increased	O
+expression	O
+of	O
+the	O
+Hol1	B-GENE
+protein	I-GENE
+.	O
+
+Damage	O
+to	O
+the	O
+BBB	O
+was	O
+judged	O
+by	O
+extravasation	O
+of	O
+Evans	O
+Blue	O
+(	O
+EB	O
+)	O
+dye	O
+,	O
+which	O
+was	O
+administered	O
+either	O
+2	O
+,	O
+3	O
+,	O
+24	O
+or	O
+48	O
+h	O
+after	O
+onset	O
+of	O
+MCAo	O
+.	O
+
+Lipid	O
+hydroperoxide	O
+levels	O
+in	O
+plasma	O
+and	O
+LDL	B-GENE
+remained	O
+unchanged	O
+throughout	O
+the	O
+study	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+vasculitis	O
+(	O
+cutaneous	O
+and	O
+neurologic	O
+)	O
+which	O
+led	O
+to	O
+the	O
+discovery	O
+of	O
+a	O
+selective	O
+immunodeficit	O
+towards	O
+EBV	O
+,	O
+similar	O
+to	O
+Purtilo	O
+'	O
+s	O
+syndrome	O
+.	O
+
+To	O
+elucidate	O
+whether	O
+potential	O
+endocrine	O
+changes	O
+resulted	O
+from	O
+acute	O
+hypoxaemia	O
+alone	O
+,	O
+the	O
+underlying	O
+disease	O
+,	O
+or	O
+unspecific	O
+influences	O
+connected	O
+with	O
+the	O
+ICU	O
+setting	O
+,	O
+all	O
+measurements	O
+were	O
+compared	O
+to	O
+those	O
+of	O
+a	O
+completely	O
+healthy	O
+reference	O
+group	O
+(	O
+REF	O
+)	O
+with	O
+comparable	O
+acute	O
+experimental	O
+hypoxaemia	O
+.	O
+
+There	O
+were	O
+no	O
+significant	O
+differences	O
+in	O
+graft	O
+survival	O
+between	O
+groups	O
+with	O
+early	O
+graft	O
+function	O
+(	O
+EGF	O
+)	O
+and	O
+DGF	O
+,	O
+either	O
+in	O
+first	O
+transplantations	O
+or	O
+retransplantations	O
+.	O
+
+These	O
+results	O
+suggested	O
+that	O
+the	O
+GG	O
+motifs	O
+contributed	O
+to	O
+the	O
+cell	O
+-	O
+specific	O
+transcription	O
+of	O
+the	O
+human	B-GENE
+insulin	I-GENE
+gene	I-GENE
+in	O
+association	O
+with	O
+the	O
+binding	O
+of	O
+the	O
+sequence	O
+-	O
+specific	O
+nuclear	O
+factor	O
+.	O
+
+Abnormal	O
+urinary	O
+coproporphyrin	O
+levels	O
+in	O
+patients	O
+infected	O
+by	O
+hepatitis	O
+C	O
+virus	O
+with	O
+or	O
+without	O
+human	O
+immunodeficiency	O
+virus	O
+.	O
+
+The	O
+determination	O
+of	O
+immunoglobulin	B-GENE
+E	I-GENE
+(	O
+IgE	B-GENE
+)	O
+antibodies	O
+by	O
+one	O
+of	O
+several	O
+laboratory	O
+tests	O
+,	O
+by	O
+skin	O
+-	O
+prick	O
+tests	O
+or	O
+by	O
+appropriate	O
+challenge	O
+procedures	O
+is	O
+useful	O
+either	O
+to	O
+identify	O
+atopic	O
+individuals	O
+or	O
+as	O
+outcome	O
+predictors	O
+in	O
+wheezy	O
+children	O
+.	O
+
+Thrombosis	O
+of	O
+the	O
+renal	O
+vein	O
+may	O
+be	O
+dramatic	O
+and	O
+include	O
+renal	O
+failure	O
+.	O
+
+Filter	O
+and	O
+cytocentrifuge	O
+preparations	O
+of	O
+the	O
+urine	O
+were	O
+studied	O
+and	O
+all	O
+cases	O
+displayed	O
+numerous	O
+scattered	O
+aggregates	O
+or	O
+single	O
+tumor	O
+cells	O
+in	O
+an	O
+inflammatory	O
+background	O
+.	O
+
+The	O
+promoter	O
+segment	O
+was	O
+inactive	O
+when	O
+introduced	O
+into	O
+the	O
+rat	O
+glioma	O
+cell	O
+line	O
+C6B4	O
+,	O
+the	O
+rat	O
+submandibular	O
+cell	O
+line	O
+RSMT	O
+-	O
+A5	O
+,	O
+and	O
+the	O
+rat	O
+pancreatic	O
+beta	O
+cell	O
+line	O
+RIN	O
+-	O
+5AH	O
+,	O
+all	O
+of	O
+which	O
+do	O
+not	O
+express	O
+the	O
+endogenous	O
+alpha2c	B-GENE
+-	I-GENE
+AR	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+sequencing	O
+of	O
+the	O
+conditional	O
+lethal	O
+mutation	O
+ts	O
+-	O
+A13	O
+,	O
+localized	O
+in	O
+the	O
+nrdE	B-GENE
+cistron	I-GENE
+,	O
+and	O
+the	O
+lethality	O
+of	O
+insertional	O
+mutations	O
+targeted	O
+in	O
+the	O
+internal	O
+region	O
+of	O
+nrdE	B-GENE
+and	O
+nrdF	B-GENE
+,	O
+demonstrated	O
+the	O
+essential	O
+role	O
+of	O
+this	O
+locus	O
+.	O
+
+The	O
+microdensitometric	O
+scores	O
+and	O
+their	O
+side	O
+-	O
+to	O
+-	O
+side	O
+differences	O
+in	O
+patients	O
+correlated	O
+negatively	O
+with	O
+the	O
+serum	O
+25	O
+-	O
+OHD	O
+concentration	O
+and	O
+positively	O
+with	O
+the	O
+degree	O
+of	O
+paralysis	O
+.	O
+
+These	O
+data	O
+do	O
+not	O
+support	O
+the	O
+use	O
+of	O
+LDD	O
+to	O
+reduce	O
+risk	O
+of	O
+progression	O
+to	O
+MSOF	O
+in	O
+sepsis	O
+.	O
+
+This	O
+correlated	O
+with	O
+reduced	O
+levels	O
+of	O
+secreted	O
+hepatitis	B-GENE
+B	I-GENE
+e	I-GENE
+antigen	I-GENE
+and	O
+increased	O
+intracellular	O
+levels	O
+of	O
+core	B-GENE
+and	O
+Pol	B-GENE
+proteins	I-GENE
+and	O
+replicative	O
+HBV	O
+DNA	O
+intermediates	O
+.	O
+
+In	O
+contrast	O
+,	O
+extracts	O
+of	O
+the	O
+mutant	O
+virions	O
+catalyze	O
+the	O
+wild	O
+-	O
+type	O
+level	O
+of	O
+transcription	O
+from	O
+an	O
+exogenous	O
+template	O
+containing	O
+an	O
+early	O
+promoter	O
+.	O
+
+The	O
+SCMV	B-GENE
+SNE	I-GENE
+sites	I-GENE
+contain	O
+potential	O
+overlapping	O
+core	O
+recognition	O
+binding	O
+motifs	O
+for	O
+SRF	B-GENE
+,	O
+Rel	B-GENE
+/	O
+NFkappaB	B-GENE
+,	O
+ETS	B-GENE
+,	O
+and	O
+YY1	B-GENE
+class	I-GENE
+transcription	I-GENE
+factors	I-GENE
+but	O
+fail	O
+to	O
+respond	O
+to	O
+either	O
+serum	O
+or	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+.	O
+
+Upon	O
+serum	O
+withdrawal	O
+at	O
+the	O
+permissive	O
+temperature	O
+,	O
+p53	B-GENE
+-	O
+mediated	O
+apoptosis	O
+was	O
+induced	O
+in	O
+50	O
+to	O
+60	O
+%	O
+of	O
+the	O
+cells	O
+.	O
+
+To	O
+circumvent	O
+this	O
+problem	O
+,	O
+a	O
+simple	O
+two	O
+-	O
+step	O
+strategy	O
+was	O
+devised	O
+by	O
+which	O
+essential	O
+cis	O
+-	O
+acting	O
+sites	O
+like	O
+the	O
+a	O
+sequence	O
+can	O
+be	O
+readily	O
+deleted	O
+from	O
+their	O
+natural	O
+loci	O
+in	O
+large	O
+viral	O
+DNA	O
+genomes	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+serological	O
+studies	O
+,	O
+the	O
+highly	O
+conserved	O
+A	O
+domain	O
+of	O
+HspA	B-GENE
+was	O
+found	O
+to	O
+be	O
+the	O
+immunodominant	O
+domain	O
+.	O
+
+In	O
+Group	O
+IV	O
+dogs	O
+that	O
+received	O
+alpha	B-GENE
+-	I-GENE
+MSH	I-GENE
+only	O
+during	O
+reperfusion	O
+,	O
+BAEPs	O
+were	O
+increased	O
+approximately	O
+10	O
+to	O
+14	O
+%	O
+more	O
+than	O
+in	O
+Group	O
+II	O
+during	O
+the	O
+late	O
+reperfusion	O
+period	O
+.	O
+
+The	O
+Fas	B-GENE
+receptor	I-GENE
+mediates	O
+a	O
+signalling	O
+cascade	O
+resulting	O
+in	O
+programmed	O
+cell	O
+death	O
+(	O
+apoptosis	O
+)	O
+within	O
+hours	O
+of	O
+receptor	O
+cross	O
+-	O
+linking	O
+.	O
+
+Fas	B-GENE
+has	O
+been	O
+shown	O
+to	O
+require	O
+ICE	B-GENE
+(	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+-	I-GENE
+converting	I-GENE
+enzyme	I-GENE
+)	O
+family	O
+proteases	O
+to	O
+induce	O
+apoptosis	O
+from	O
+studies	O
+utilizing	O
+the	O
+cowpox	O
+ICE	B-GENE
+inhibitor	I-GENE
+protein	I-GENE
+CrmA	B-GENE
+,	O
+the	O
+synthetic	O
+tetrapeptide	O
+ICE	B-GENE
+inhibitor	O
+YVAD	B-GENE
+-	I-GENE
+CMK	I-GENE
+,	O
+and	O
+the	O
+tripeptide	O
+pan	O
+-	O
+ICE	B-GENE
+inhibitor	O
+Z	B-GENE
+-	I-GENE
+VAD	I-GENE
+-	I-GENE
+FMK	I-GENE
+.	O
+
+The	O
+imprinted	O
+expression	O
+of	O
+the	O
+endogenous	O
+gene	O
+can	O
+be	O
+recapitulated	O
+in	O
+mice	O
+by	O
+using	O
+a	O
+14	O
+-	O
+kb	O
+transgene	O
+encompassing	O
+4	O
+kb	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+sequence	O
+,	O
+8	O
+kb	O
+of	O
+3	O
+'	O
+-	O
+flanking	O
+sequence	O
+,	O
+which	O
+includes	O
+the	O
+two	O
+endoderm	O
+-	O
+specific	O
+enhancers	O
+,	O
+and	O
+an	O
+internally	O
+deleted	O
+structural	O
+gene	O
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+demonstrate	O
+that	O
+hGCN5	B-GENE
+is	O
+also	O
+an	O
+HAT	B-GENE
+and	O
+has	O
+the	O
+same	O
+substrate	O
+specificity	O
+as	O
+yGCN5	B-GENE
+.	O
+
+Complementary	O
+DNAs	O
+encompassing	O
+the	O
+coat	B-GENE
+protein	I-GENE
+coding	O
+and	O
+adjacent	O
+regions	O
+of	O
+Agropyron	O
+mosaic	O
+virus	O
+(	O
+AgMV	O
+)	O
+and	O
+Hordeum	O
+mosaic	O
+virus	O
+(	O
+HoMV	O
+)	O
+were	O
+cloned	O
+and	O
+sequenced	O
+.	O
+
+In	O
+some	O
+cases	O
+,	O
+factor	O
+-	O
+induced	O
+Rac	B-GENE
+activation	O
+results	O
+in	O
+Rho	B-GENE
+activation	O
+,	O
+and	O
+factor	O
+-	O
+induced	O
+Cdc42	B-GENE
+activation	O
+leads	O
+to	O
+Rac	B-GENE
+activation	O
+,	O
+as	O
+determined	O
+by	O
+specific	O
+morphological	O
+changes	O
+.	O
+
+Several	O
+cDNAs	O
+corresponding	O
+to	O
+the	O
+human	B-GENE
+PWP2	I-GENE
+gene	I-GENE
+were	O
+identified	O
+and	O
+partially	O
+sequenced	O
+.	O
+
+Isolation	O
+and	O
+genomic	O
+structure	O
+of	O
+a	O
+human	O
+homolog	O
+of	O
+the	O
+yeast	B-GENE
+periodic	I-GENE
+tryptophan	I-GENE
+protein	I-GENE
+2	I-GENE
+(	O
+PWP2	B-GENE
+)	O
+gene	O
+mapping	O
+to	O
+21q22	O
+.	O
+3	O
+.	O
+
+Patterns	O
+defined	O
+by	O
+combinations	O
+of	O
+normal	O
+and	O
+abnormal	O
+laboratory	O
+results	O
+had	O
+decreased	O
+the	O
+likelihood	O
+of	O
+PEM	O
+from	O
+an	O
+all	O
+-	O
+2	O
+to	O
+all	O
+-	O
+0	O
+pattern	O
+.	O
+
+To	O
+examine	O
+whether	O
+thiamine	O
+(	O
+vitamin	O
+B1	O
+)	O
+deficiency	O
+is	O
+associated	O
+with	O
+recurrent	O
+aphthous	O
+stomatitis	O
+,	O
+we	O
+studied	O
+vitamin	O
+B1	O
+levels	O
+in	O
+70	O
+patients	O
+with	O
+recurrent	O
+aphthous	O
+stomatitis	O
+and	O
+in	O
+50	O
+members	O
+of	O
+a	O
+control	O
+group	O
+.	O
+
+Liver	O
+injuries	O
+
+By	O
+screening	O
+a	O
+cDNA	O
+library	O
+with	O
+a	O
+probe	O
+derived	O
+from	O
+sequences	O
+downstream	O
+of	O
+the	O
+p53p2	B-GENE
+start	O
+site	O
+,	O
+we	O
+have	O
+cloned	O
+and	O
+characterized	O
+a	O
+cDNA	O
+that	O
+represents	O
+a	O
+mRNA	O
+that	O
+appears	O
+to	O
+have	O
+been	O
+initiated	O
+from	O
+the	O
+p53p2	B-GENE
+promoter	I-GENE
+.	O
+
+However	O
+,	O
+we	O
+did	O
+not	O
+observe	O
+a	O
+correlation	O
+between	O
+serum	O
+and	O
+seminal	B-GENE
+plasma	I-GENE
+PSA	I-GENE
+levels	O
+.	O
+
+The	O
+implications	O
+for	O
+estimates	O
+of	O
+cortical	O
+magnification	O
+and	O
+possible	O
+differences	O
+in	O
+the	O
+specializations	O
+of	O
+foveal	O
+and	O
+peripheral	O
+vision	O
+are	O
+discussed	O
+.	O
+
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+activates	O
+multiple	O
+signaling	O
+molecules	O
+,	O
+including	O
+the	O
+JAK1	B-GENE
+and	O
+JAK2	B-GENE
+kinases	I-GENE
+and	O
+the	O
+STAT	B-GENE
+transcription	O
+factors	O
+.	O
+
+Mutants	O
+lacking	O
+any	O
+tyrosine	O
+residues	O
+in	O
+the	O
+cytoplasmic	O
+domain	O
+maintain	O
+their	O
+ability	O
+to	O
+activate	O
+STAT5	B-GENE
+and	O
+STAT1	B-GENE
+but	O
+cannot	O
+activate	O
+STAT3	B-GENE
+,	O
+implying	O
+that	O
+STAT5	B-GENE
+and	O
+STAT1	B-GENE
+activation	O
+does	O
+not	O
+require	O
+receptor	O
+tyrosine	O
+phosphorylation	O
+.	O
+
+In	O
+addition	O
+,	O
+double	O
+mutants	O
+with	O
+either	O
+dim1	B-GENE
+-	I-GENE
+delta	I-GENE
+or	O
+dim2	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+the	O
+endocytosis	O
+mutants	B-GENE
+end4	I-GENE
+-	I-GENE
+1	I-GENE
+or	O
+act1	B-GENE
+-	I-GENE
+1	I-GENE
+displayed	O
+synthetic	O
+growth	O
+defects	O
+,	O
+indicating	O
+that	O
+the	O
+DIM	B-GENE
+gene	I-GENE
+products	I-GENE
+function	O
+in	O
+a	O
+common	O
+or	O
+parallel	O
+endocytic	O
+pathway	O
+.	O
+
+Such	O
+multisensory	O
+interactions	O
+can	O
+be	O
+significant	O
+for	O
+behavior	O
+.	O
+
+The	O
+P13	O
+and	O
+N22	O
+of	O
+ppSEPs	O
+had	O
+phase	O
+reversal	O
+relationship	O
+with	O
+the	O
+P2	O
+and	O
+N2	O
+recorded	O
+from	O
+the	O
+PES	O
+,	O
+respectively	O
+.	O
+
+The	O
+cDNA	O
+of	O
+cpm7	B-GENE
+encodes	O
+a	O
+closely	O
+related	O
+protein	O
+of	O
+36	O
+.	O
+8	O
+kDa	O
+.	O
+
+Finally	O
+,	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+ENBP1	B-GENE
+shows	O
+strong	O
+homology	O
+to	O
+a	O
+protein	O
+from	O
+rat	O
+that	O
+is	O
+specifically	O
+expressed	O
+in	O
+testis	O
+tissue	O
+.	O
+
+The	O
+conservation	O
+of	O
+both	O
+the	O
+G	O
+-	O
+box	O
+and	O
+H	O
+-	O
+box	O
+in	O
+different	O
+CHS	B-GENE
+promoters	I-GENE
+emphasizes	O
+their	O
+importance	O
+as	O
+regulatory	O
+motifs	O
+.	O
+
+Mortality	O
+on	O
+the	O
+last	O
+ranch	O
+was	O
+particularly	O
+severe	O
+among	O
+certain	O
+segregated	O
+groups	O
+of	O
+turkeys	O
+that	O
+included	O
+toms	O
+,	O
+heavier	O
+birds	O
+,	O
+and	O
+birds	O
+undergoing	O
+a	O
+stressful	O
+event	O
+such	O
+as	O
+artificial	O
+insemination	O
+.	O
+
+Further	O
+,	O
+the	O
+PIP2	O
+content	O
+of	O
+the	O
+85	O
+-	O
+90	O
+kDa	O
+protein	O
+appeared	O
+to	O
+decrease	O
+with	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+treatment	O
+.	O
+
+Further	O
+,	O
+the	O
+PIP2	O
+content	O
+of	O
+the	O
+85	O
+-	O
+90	O
+kDa	O
+protein	O
+appeared	O
+to	O
+decrease	O
+with	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+treatment	O
+.	O
+
+Just	O
+before	O
+inserting	O
+on	O
+the	O
+anterior	O
+margin	O
+and	O
+apex	O
+of	O
+the	O
+iliac	O
+crest	O
+it	O
+widens	O
+,	O
+assuming	O
+the	O
+aspect	O
+of	O
+a	O
+small	O
+cone	O
+.	O
+
+Reperfusion	O
+caused	O
+a	O
+transient	O
+reduction	O
+in	O
+lactate	O
+production	O
+and	O
+a	O
+significant	O
+increase	O
+in	O
+LDH	B-GENE
+release	O
+.	O
+
+To	O
+evaluate	O
+the	O
+hepatic	O
+regenerative	O
+response	O
+in	O
+patients	O
+with	O
+alcoholic	O
+liver	O
+disease	O
+,	O
+sera	O
+from	O
+263	O
+patients	O
+with	O
+severe	O
+alcoholic	O
+hepatitis	O
+and	O
+/	O
+or	O
+cirrhosis	O
+were	O
+analyzed	O
+for	O
+hepatocyte	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+HGF	B-GENE
+)	O
+and	O
+alpha	B-GENE
+-	I-GENE
+fetoprotein	I-GENE
+(	O
+AFP	B-GENE
+)	O
+.	O
+
+Children	O
+born	O
+from	O
+chronic	O
+alcoholic	O
+mothers	O
+have	O
+shown	O
+behavioral	O
+teratogenic	O
+effects	O
+more	O
+frequently	O
+than	O
+morphological	O
+malformations	O
+.	O
+
+INTERVENTION	O
+(	O
+S	O
+)	O
+:	O
+Twenty	O
+-	O
+six	O
+hemostasis	O
+parameters	O
+evaluated	O
+repeatedly	O
+in	O
+patients	O
+undergoing	O
+IVF	O
+-	O
+ET	O
+.	O
+
+Here	O
+we	O
+report	O
+that	O
+expression	O
+of	O
+the	O
+I	B-GENE
+-	I-GENE
+POU	I-GENE
+/	O
+tI	B-GENE
+-	I-GENE
+POU	I-GENE
+message	O
+is	O
+maximal	O
+late	O
+in	O
+the	O
+embryonic	O
+phase	O
+of	O
+Drosophila	O
+development	O
+,	O
+and	O
+I	B-GENE
+-	I-GENE
+POU	I-GENE
+is	O
+the	O
+preferred	O
+splice	O
+variant	O
+.	O
+
+The	O
+patient	O
+'	O
+s	O
+role	O
+,	O
+organized	O
+by	O
+the	O
+prerequisites	O
+of	O
+expressive	O
+freedom	O
+,	O
+is	O
+counter	O
+posed	O
+with	O
+the	O
+psychoanalyst	O
+'	O
+s	O
+,	O
+which	O
+is	O
+structured	O
+to	O
+empower	O
+listening	O
+and	O
+understanding	O
+.	O
+
+The	O
+most	O
+common	O
+risk	O
+factor	O
+reported	O
+for	O
+both	O
+recent	O
+and	O
+all	O
+other	O
+hepatitis	O
+C	O
+cases	O
+was	O
+a	O
+history	O
+of	O
+injecting	O
+drug	O
+use	O
+,	O
+although	O
+the	O
+proportion	O
+of	O
+cases	O
+with	O
+that	O
+history	O
+was	O
+different	O
+in	O
+NT	O
+from	O
+ACT	O
+and	O
+Queensland	O
+.	O
+
+Silencing	O
+can	O
+be	O
+restored	O
+by	O
+creation	O
+of	O
+a	O
+telomere	O
+at	O
+13	O
+kb	O
+from	O
+the	O
+reporter	O
+construct	O
+,	O
+or	O
+by	O
+insertion	O
+of	O
+340	O
+bp	O
+of	O
+yeast	O
+telomeric	O
+repeat	O
+sequence	O
+at	O
+this	O
+site	O
+without	O
+chromosomal	O
+truncation	O
+.	O
+
+In	O
+contrast	O
+with	O
+previous	O
+two	O
+-	O
+pool	O
+models	O
+,	O
+provisions	O
+were	O
+made	O
+for	O
+folate	O
+turnover	O
+by	O
+urinary	O
+folate	O
+excretion	O
+(	O
+as	O
+measured	O
+here	O
+)	O
+and	O
+by	O
+fecal	O
+excretion	O
+and	O
+catabolic	O
+processes	O
+.	O
+
+When	O
+voltage	O
+-	O
+operated	O
+Ca2	O
++	O
+channels	O
+(	O
+VOC	O
+)	O
+were	O
+blocked	O
+by	O
+nifedipine	O
+,	O
+midazolam	O
+,	O
+in	O
+concentrations	O
+more	O
+than	O
+1	O
+microM	O
+,	O
+attenuated	O
+both	O
+phasic	O
+and	O
+tonic	O
+responses	O
+.	O
+
+Although	O
+p48	B-GENE
+gene	I-GENE
+induction	O
+is	O
+dependent	O
+on	O
+STAT1	B-GENE
+and	O
+JAK1	B-GENE
+,	O
+activated	O
+STAT1	B-GENE
+does	O
+not	O
+bind	O
+to	O
+GATE	B-GENE
+.	O
+
+The	O
+syndrome	O
+of	O
+resistance	O
+to	O
+thyroid	O
+hormone	O
+is	O
+characterized	O
+by	O
+elevated	O
+serum	O
+free	O
+thyroid	O
+hormones	O
+,	O
+failure	O
+to	O
+suppress	O
+pituitary	B-GENE
+thyrotropin	I-GENE
+secretion	O
+,	O
+and	O
+variable	O
+peripheral	O
+refractoriness	O
+to	O
+hormone	O
+action	O
+.	O
+
+Finally	O
+,	O
+nonphotosynthetic	O
+mutants	O
+,	O
+including	O
+the	O
+tscA	B-GENE
+-	I-GENE
+lacking	I-GENE
+photosystem	I-GENE
+I	I-GENE
+mutant	I-GENE
+,	O
+H13	O
+,	O
+did	O
+not	O
+show	O
+evidence	O
+of	O
+light	O
+-	O
+stimulated	O
+RNA	O
+processing	O
+.	O
+
+The	O
+progression	O
+of	O
+acute	O
+bronchitis	O
+is	O
+associated	O
+with	O
+elevated	O
+blood	O
+concentrations	O
+of	O
+acute	O
+-	O
+phase	O
+proteins	O
+,	O
+KKS	B-GENE
+activation	O
+in	O
+the	O
+blood	O
+and	O
+high	O
+serotonin	O
+and	O
+lactic	O
+acid	O
+content	O
+in	O
+the	O
+humor	O
+condensated	O
+from	O
+the	O
+exhaled	O
+air	O
+.	O
+
+Because	O
+of	O
+the	O
+potential	O
+implications	O
+of	O
+these	O
+findings	O
+in	O
+human	O
+physiology	O
+,	O
+we	O
+cloned	O
+the	O
+hPACAP	B-GENE
+-	I-GENE
+R	I-GENE
+gene	I-GENE
+.	O
+
+Differential	O
+signaling	O
+and	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+gene	I-GENE
+activation	O
+by	O
+four	O
+splice	O
+variants	O
+of	O
+the	O
+human	B-GENE
+pituitary	I-GENE
+adenylate	I-GENE
+cyclase	I-GENE
+-	I-GENE
+activating	I-GENE
+polypeptide	I-GENE
+receptor	I-GENE
+(	O
+hPACAP	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+.	O
+
+We	O
+discuss	O
+these	O
+results	O
+with	O
+respect	O
+to	O
+the	O
+transcriptional	O
+induction	O
+of	O
+the	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+alpha	I-GENE
+gene	I-GENE
+in	O
+respiratory	O
+epithelium	O
+during	O
+embryogenesis	O
+.	O
+
+BACKGROUND	O
+:	O
+Mitosis	O
+is	O
+regulated	O
+by	O
+MPF	B-GENE
+(	O
+maturation	B-GENE
+promoting	I-GENE
+factor	I-GENE
+)	O
+,	O
+the	O
+active	O
+form	O
+of	O
+Cdc2	B-GENE
+/	I-GENE
+28	I-GENE
+-	O
+cyclin	B-GENE
+B	I-GENE
+complexes	O
+.	O
+
+Ectopic	O
+expression	O
+of	O
+Apo	B-GENE
+-	I-GENE
+3	I-GENE
+in	O
+HEK293	O
+or	O
+HeLa	O
+cells	O
+induced	O
+marked	O
+apoptosis	O
+.	O
+
+An	O
+N	O
+-	O
+terminal	O
+arm	O
+from	O
+each	O
+subunit	O
+wraps	O
+around	O
+the	O
+dinucleotide	O
+-	O
+binding	O
+domain	O
+of	O
+an	O
+adjacent	O
+subunit	O
+,	O
+covering	O
+the	O
+adenine	O
+ring	O
+of	O
+NADP	O
+.	O
+
+Similarity	O
+is	O
+most	O
+striking	O
+in	O
+the	O
+zinc	O
+knuckle	O
+region	O
+,	O
+a	O
+region	O
+characteristic	O
+of	O
+gag	B-GENE
+genes	I-GENE
+of	O
+most	O
+replication	O
+-	O
+competent	O
+retroelements	O
+.	O
+
+D	O
+.	O
+melanogaster	O
+HeT	B-GENE
+-	I-GENE
+A	I-GENE
+coding	O
+sequences	O
+have	O
+a	O
+polymorphic	O
+region	O
+with	O
+insertions	O
+/	O
+deletions	O
+of	O
+1	O
+-	O
+31	O
+codons	O
+and	O
+many	O
+nucleotide	O
+changes	O
+.	O
+
+Eukaryotic	B-GENE
+initiation	I-GENE
+factor	I-GENE
+3	I-GENE
+(	O
+eIF3	B-GENE
+)	O
+is	O
+a	O
+large	O
+multisubunit	O
+complex	O
+that	O
+stabilizes	O
+the	O
+ternary	O
+complex	O
+,	O
+eIF2	B-GENE
+x	O
+GTP	O
+x	O
+tRNA	B-GENE
+(	I-GENE
+Met	I-GENE
+)	I-GENE
+i	I-GENE
+and	O
+promotes	O
+mRNA	O
+binding	O
+to	O
+the	O
+40	B-GENE
+S	I-GENE
+ribosomal	I-GENE
+subunit	I-GENE
+.	O
+eIF3	B-GENE
+also	O
+functions	O
+as	O
+a	O
+ribosome	O
+subunit	O
+anti	O
+-	O
+association	O
+factor	O
+.	O
+
+Our	O
+data	O
+,	O
+combined	O
+with	O
+those	O
+of	O
+Hershey	O
+and	O
+co	O
+-	O
+workers	O
+,	O
+suggest	O
+that	O
+mammalian	B-GENE
+eIF3	I-GENE
+is	O
+composed	O
+of	O
+at	O
+least	O
+10	O
+subunits	O
+:	O
+p170	B-GENE
+,	O
+p116	B-GENE
+(	O
+hPrt1	B-GENE
+)	O
+,	O
+p110	B-GENE
+,	O
+p66	B-GENE
+,	O
+p48	B-GENE
+,	O
+p47	B-GENE
+,	O
+p44	B-GENE
+,	O
+p40	B-GENE
+,	O
+p36	B-GENE
+,	O
+and	O
+p35	B-GENE
+.	O
+
+Identification	O
+of	O
+a	O
+cis	O
+-	O
+acting	O
+element	O
+in	O
+the	O
+class	B-GENE
+I	I-GENE
+major	I-GENE
+histocompatibility	I-GENE
+complex	I-GENE
+gene	I-GENE
+promoter	I-GENE
+responsive	O
+to	O
+activation	O
+by	O
+retroviral	O
+sequences	O
+.	O
+
+The	O
+results	O
+demonstrate	O
+that	O
+(	O
+i	O
+)	O
+no	O
+intact	O
+capsids	O
+were	O
+assembled	O
+when	O
+the	O
+full	O
+-	O
+length	O
+or	O
+a	O
+truncated	O
+(	O
+missing	O
+the	O
+C	O
+-	O
+terminal	O
+65	O
+amino	O
+acids	O
+)	O
+UL80	B-GENE
+.	I-GENE
+5	I-GENE
+protein	I-GENE
+was	O
+tested	O
+;	O
+(	O
+ii	O
+)	O
+when	O
+the	O
+C	O
+-	O
+terminal	O
+65	O
+amino	O
+acids	O
+of	O
+the	O
+UL80	B-GENE
+.	I-GENE
+5	I-GENE
+protein	I-GENE
+were	O
+replaced	O
+with	O
+the	O
+C	O
+-	O
+terminal	O
+25	O
+amino	O
+acids	O
+of	O
+the	O
+UL26	B-GENE
+.	I-GENE
+5	I-GENE
+protein	I-GENE
+,	O
+intact	O
+capsids	O
+were	O
+made	O
+and	O
+direct	O
+interaction	O
+of	O
+the	O
+UL80	B-GENE
+.	I-GENE
+5	I-GENE
+protein	I-GENE
+with	O
+VP5	B-GENE
+was	O
+detected	O
+;	O
+(	O
+iii	O
+)	O
+assembly	O
+of	O
+intact	O
+capsids	O
+was	O
+demonstrated	O
+when	O
+the	O
+sequence	O
+of	O
+the	O
+last	O
+12	O
+amino	O
+acids	O
+of	O
+the	O
+UL80	B-GENE
+.	I-GENE
+5	I-GENE
+protein	I-GENE
+was	O
+changed	O
+from	O
+RRIFVA	O
+ALNKLE	O
+to	O
+RRIFVAAMMKLE	O
+;	O
+(	O
+iv	O
+)	O
+self	O
+-	O
+interaction	O
+of	O
+the	O
+scaffold	O
+proteins	O
+is	O
+mediated	O
+by	O
+sequences	O
+N	O
+terminal	O
+to	O
+the	O
+maturation	O
+cleavage	O
+site	O
+;	O
+and	O
+(	O
+v	O
+)	O
+the	O
+UL26	B-GENE
+.	I-GENE
+5	I-GENE
+and	O
+UL80	B-GENE
+.	I-GENE
+5	I-GENE
+proteins	I-GENE
+will	O
+not	O
+coassemble	O
+into	O
+scaffold	O
+structures	O
+.	O
+
+Fourth	O
+,	O
+the	O
+3	O
+'	O
+-	O
+region	O
+splice	O
+junctions	O
+of	O
+the	O
+MSRs	B-GENE
+during	O
+latent	O
+and	O
+productive	O
+infection	O
+were	O
+determined	O
+by	O
+sequencing	O
+RNA	O
+-	O
+PCR	O
+products	O
+generated	O
+with	O
+primers	O
+that	O
+flank	O
+the	O
+3	O
+'	O
+splice	O
+region	O
+.	O
+
+(	O
+ii	O
+)	O
+ICP27	B-GENE
+binds	O
+preferentially	O
+to	O
+less	O
+modified	O
+forms	O
+of	O
+ICP4	B-GENE
+,	O
+a	O
+protein	O
+that	O
+is	O
+extensively	O
+modified	O
+posttranslationally	O
+.	O
+
+Lack	O
+of	O
+sufficient	O
+data	O
+on	O
+vibration	O
+measurements	O
+and	O
+employment	O
+durations	O
+add	O
+to	O
+the	O
+uncertainty	O
+,	O
+as	O
+do	O
+variations	O
+in	O
+tool	O
+conditions	O
+(	O
+grinder	O
+wheels	O
+,	O
+etc	O
+)	O
+and	O
+inherent	O
+difficulties	O
+in	O
+measurement	O
+.	O
+
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+V	I-GENE
+>	O
+A	O
+selectively	O
+binds	O
+only	O
+the	O
+subset	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+sites	I-GENE
+that	O
+are	O
+also	O
+DBP	B-GENE
+sites	I-GENE
+,	O
+both	O
+as	O
+oligonucleotides	O
+and	O
+within	O
+the	O
+natural	O
+contexts	O
+of	O
+the	O
+albumin	B-GENE
+and	O
+cholesterol	B-GENE
+hydroxylase	I-GENE
+promoters	I-GENE
+.	O
+
+Specific	O
+IgG	B-GENE
+,	O
+specific	O
+IgE	B-GENE
+and	O
+total	O
+IgE	B-GENE
+immunoglobulins	I-GENE
+against	O
+Toxocara	B-GENE
+canis	I-GENE
+excretory	I-GENE
+/	I-GENE
+secretory	I-GENE
+antigens	I-GENE
+(	O
+TES	B-GENE
+)	O
+were	O
+detected	O
+by	O
+using	O
+ELISA	O
+technique	O
+.	O
+
+SUMMARY	O
+BACKGROUND	O
+DATA	O
+:	O
+Melanoma	O
+care	O
+has	O
+not	O
+changed	O
+significantly	O
+in	O
+the	O
+last	O
+20	O
+years	O
+,	O
+and	O
+the	O
+controversy	O
+of	O
+elective	O
+lymph	O
+node	O
+dissections	O
+in	O
+this	O
+disease	O
+continues	O
+to	O
+be	O
+discussed	O
+.	O
+
+The	O
+differences	O
+among	O
+subgenera	O
+of	O
+the	O
+genus	O
+Dermacentor	O
+are	O
+more	O
+significant	O
+.	O
+
+Mutating	O
+the	O
+E	O
+-	O
+box	O
+in	O
+the	O
+context	O
+of	O
+the	O
+3	O
+'	O
+-	O
+flanking	O
+region	O
+confirmed	O
+that	O
+it	O
+contributes	O
+to	O
+the	O
+enhancement	O
+of	O
+transcriptional	O
+activity	O
+of	O
+the	O
+alpha1	B-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+collagen	I-GENE
+gene	I-GENE
+promoter	I-GENE
+.	O
+
+Expression	O
+of	O
+neuronal	O
+traits	O
+in	O
+pancreatic	O
+beta	O
+cells	O
+.	O
+
+We	O
+propose	O
+that	O
+Mnt	B-GENE
+:	O
+Max	B-GENE
+:	O
+Sin3	B-GENE
+complexes	O
+normally	O
+function	O
+to	O
+restrict	O
+Myc	B-GENE
+:	O
+Max	B-GENE
+activities	O
+associated	O
+with	O
+cell	O
+proliferation	O
+.	O
+
+Phenotypic	O
+changes	O
+induced	O
+by	O
+wild	B-GENE
+type	I-GENE
+and	I-GENE
+variant	I-GENE
+c	I-GENE
+-	I-GENE
+src	I-GENE
+genes	I-GENE
+carrying	O
+C	O
+-	O
+terminal	O
+sequence	O
+alterations	O
+.	O
+
+The	O
+resurgence	O
+of	O
+drug	O
+-	O
+resistant	O
+malaria	O
+makes	O
+urgent	O
+the	O
+evaluation	O
+of	O
+new	O
+antimalarial	O
+agents	O
+.	O
+
+In	O
+the	O
+p51	B-GENE
+subunit	I-GENE
+,	O
+the	O
+Cys181	O
+side	O
+-	O
+chain	O
+is	O
+oriented	O
+in	O
+a	O
+similar	O
+direction	O
+to	O
+the	O
+Tyr181	O
+side	O
+-	O
+chain	O
+in	O
+the	O
+wild	O
+-	O
+type	O
+complex	O
+.	O
+
+The	O
+relatively	O
+high	O
+level	O
+transcription	O
+from	O
+this	O
+gene	O
+shows	O
+that	O
+the	O
+polymorphic	O
+chromosome	O
+ends	O
+of	O
+P	O
+.	O
+falciparum	O
+,	O
+which	O
+have	O
+been	O
+proposed	O
+to	O
+be	O
+transcriptionally	O
+silent	O
+,	O
+can	O
+be	O
+active	O
+expression	O
+sites	O
+for	O
+var	B-GENE
+genes	I-GENE
+.	O
+
+NUP145	B-GENE
+was	O
+previously	O
+identified	O
+by	O
+using	O
+a	O
+genetic	O
+synthetic	O
+lethal	O
+screen	O
+(	O
+E	O
+.	O
+
+Prevalence	O
+of	O
+sleep	O
+-	O
+disordered	O
+breathing	O
+(	O
+SDB	O
+)	O
+is	O
+reported	O
+to	O
+increase	O
+in	O
+menopausal	O
+women	O
+.	O
+
+In	O
+all	O
+cases	O
+the	O
+antigenemia	O
+was	O
+transient	O
+and	O
+cleared	O
+by	O
+28th	O
+day	O
+post	O
+-	O
+vaccination	O
+.	O
+
+A	O
+total	O
+of	O
+1459	O
+men	O
+aged	O
+48	O
+to	O
+84	O
+years	O
+,	O
+who	O
+were	O
+diagnosed	O
+for	O
+the	O
+first	O
+time	O
+by	O
+physicians	O
+as	O
+having	O
+BPH	O
+in	O
+1994	O
+and	O
+who	O
+had	O
+not	O
+received	O
+treatment	O
+,	O
+participated	O
+in	O
+the	O
+study	O
+.	O
+
+In	O
+vitro	O
+translation	O
+of	O
+the	O
+mTRF1	B-GENE
+cDNA	I-GENE
+resulted	O
+in	O
+a	O
+56	O
+kDa	O
+protein	O
+that	O
+binds	O
+to	O
+TTAGGG	O
+repeat	O
+arrays	O
+.	O
+mTRF1	B-GENE
+displayed	O
+the	O
+same	O
+sequence	O
+specificity	O
+as	O
+hTRF1	B-GENE
+,	O
+preferring	O
+arrays	O
+of	O
+TTAGGG	O
+repeats	O
+as	O
+a	O
+binding	O
+substrate	O
+over	O
+TTAGGC	O
+and	O
+TTGGGG	O
+repeats	O
+.	O
+
+The	O
+ubiquitously	O
+expressed	O
+E12	B-GENE
+bHLH	I-GENE
+protein	I-GENE
+dimerizes	O
+with	O
+numerous	O
+cell	O
+-	O
+specific	O
+bHLH	B-GENE
+factors	I-GENE
+.	O
+
+The	O
+E	O
+-	O
+box	O
+sequence	O
+in	O
+the	O
+SE2	B-GENE
+fragment	I-GENE
+of	O
+the	O
+transferrin	B-GENE
+promoter	I-GENE
+was	O
+CATCTG	O
+and	O
+was	O
+similar	O
+in	O
+gel	O
+shifts	O
+to	O
+the	O
+consensus	O
+E	O
+-	O
+box	O
+elements	O
+(	O
+CANNTG	O
+)	O
+previously	O
+characterized	O
+.	O
+
+A	O
+5	O
+.	O
+3	O
+-	O
+kb	O
+DNA	O
+fragment	O
+,	O
+which	O
+included	O
+the	O
+entire	O
+structural	O
+porin	B-GENE
+gene	I-GENE
+(	O
+named	O
+porCa	B-GENE
+)	O
+and	O
+its	O
+flanking	O
+regions	O
+,	O
+was	O
+identified	O
+.	O
+
+The	O
+human	B-GENE
+p100	I-GENE
+protein	I-GENE
+was	O
+recently	O
+identified	O
+as	O
+a	O
+coactivator	O
+of	O
+the	O
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+nuclear	I-GENE
+antigen	I-GENE
+2	I-GENE
+.	O
+
+However	O
+,	O
+five	O
+new	O
+mutation	O
+sites	O
+(	O
+S61	B-GENE
+,	O
+SL1	B-GENE
+,	O
+S29	B-GENE
+,	O
+SL11	B-GENE
+,	O
+SL196	B-GENE
+and	O
+SL126	B-GENE
+)	O
+are	O
+unique	O
+to	O
+the	O
+nrdB	B-GENE
+intron	O
+and	O
+disrupt	O
+self	O
+-	O
+splicing	O
+.	O
+
+This	O
+report	O
+presents	O
+the	O
+isolation	O
+and	O
+characterization	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+(	O
+1	O
+.	O
+2	O
+kb	O
+)	O
+and	O
+exon	O
+1	O
+of	O
+the	O
+human	B-GENE
+RII	I-GENE
+alpha	I-GENE
+gene	I-GENE
+.	O
+
+A	O
+cohort	O
+of	O
+Swedish	O
+children	O
+was	O
+monitored	O
+from	O
+6	O
+months	O
+to	O
+11	O
+years	O
+of	O
+age	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+assess	O
+the	O
+reproducibility	O
+of	O
+a	O
+number	O
+of	O
+simplified	O
+clearance	O
+methods	O
+using	O
+chromium	O
+-	O
+51	O
+ethylenediamine	O
+tetraacetic	O
+acid	O
+(	O
+51Cr	O
+-	O
+EDTA	O
+)	O
+and	O
+to	O
+compare	O
+these	O
+with	O
+the	O
+multiple	O
+blood	O
+sample	O
+technique	O
+.	O
+
+The	O
+primary	O
+structure	O
+of	O
+a	O
+2671	O
+bp	O
+DNA	O
+fragment	O
+between	O
+the	O
+pla	B-GENE
+gene	I-GENE
+(	O
+encoding	O
+plasminogen	B-GENE
+activator	I-GENE
+)	O
+and	O
+the	O
+origin	O
+of	O
+replication	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+Yersinia	O
+pestis	O
+plasmid	O
+pYP358	O
+was	O
+determined	O
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURES	O
+:	O
+Associations	O
+of	O
+factor	O
+analysis	O
+-	O
+derived	O
+syndromes	O
+with	O
+risk	O
+factors	O
+for	O
+chemical	O
+interactions	O
+that	O
+inhibit	O
+butyrylcholinesterase	B-GENE
+and	O
+neuropathy	O
+target	O
+esterase	B-GENE
+.	O
+
+CONCLUSION	O
+:	O
+Some	O
+Gulf	O
+War	O
+veterans	O
+may	O
+have	O
+delayed	O
+,	O
+chronic	O
+neurotoxic	O
+syndromes	O
+from	O
+wartime	O
+exposure	O
+to	O
+combinations	O
+of	O
+chemicals	O
+that	O
+inhibit	O
+butyrylcholinesterase	B-GENE
+and	O
+neuropathy	B-GENE
+target	I-GENE
+esterase	I-GENE
+.	O
+
+No	O
+correlation	O
+between	O
+the	O
+age	O
+of	O
+the	O
+horses	O
+and	O
+the	O
+antibody	O
+level	O
+could	O
+be	O
+found	O
+.	O
+
+The	O
+GHR	B-GENE
+mRNA	I-GENE
+:	O
+GHBP	B-GENE
+mRNA	I-GENE
+ratio	O
+was	O
+1	O
+.	O
+1	O
++	O
+/	O
+-	O
+0	O
+.	O
+12	O
+and	O
+remained	O
+unchanged	O
+during	O
+differentiation	O
+.	O
+
+The	O
+results	O
+demonstrate	O
+(	O
+i	O
+)	O
+that	O
+the	O
+selenocysteine	O
+-	O
+specific	O
+UGA	O
+codon	O
+is	O
+readily	O
+suppressed	O
+under	O
+conditions	O
+where	O
+the	O
+homologous	B-GENE
+SelB	I-GENE
+protein	I-GENE
+is	O
+absent	O
+and	O
+(	O
+ii	O
+)	O
+that	O
+apart	O
+from	O
+the	O
+specificity	O
+of	O
+the	O
+SelB	B-GENE
+-	I-GENE
+mRNA	I-GENE
+interaction	O
+,	O
+a	O
+structural	O
+compatibility	O
+of	O
+the	O
+quaternary	O
+complex	O
+with	O
+the	O
+ribosome	O
+is	O
+required	O
+.	O
+
+One	O
+linker	O
+-	O
+peptide	O
+insertion	O
+in	O
+the	O
+RsaA	B-GENE
+C	I-GENE
+terminus	I-GENE
+(	I-GENE
+amino	I-GENE
+acid	I-GENE
+784	I-GENE
+)	I-GENE
+had	O
+no	O
+effect	O
+on	O
+S	O
+-	O
+layer	O
+biogenesis	O
+,	O
+while	O
+another	O
+(	O
+amino	O
+acid	O
+907	O
+)	O
+disrupted	O
+secretion	O
+of	O
+the	O
+protein	O
+,	O
+suggesting	O
+that	O
+RsaA	B-GENE
+possesses	O
+a	O
+secretion	O
+signal	O
+lying	O
+C	O
+terminal	O
+to	O
+amino	O
+acid	O
+784	O
+,	O
+near	O
+or	O
+including	O
+amino	O
+acid	O
+907	O
+.	O
+
+To	O
+characterize	O
+the	O
+gene	O
+products	O
+,	O
+the	O
+cvaA	B-GENE
+gene	I-GENE
+was	O
+subcloned	O
+and	O
+expressed	O
+under	O
+the	O
+control	O
+of	O
+T7	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+promoter	I-GENE
+.	O
+
+PrpB	B-GENE
+showed	O
+homology	O
+to	O
+carboxyphosphonoenolpyruvate	B-GENE
+phosphonomutase	I-GENE
+of	I-GENE
+Streptomyces	I-GENE
+hygroscopicus	I-GENE
+and	O
+to	O
+its	O
+homolog	O
+in	O
+the	O
+carnation	O
+Dianthus	O
+caryophyllus	O
+;	O
+PrpC	B-GENE
+was	O
+homologous	O
+to	O
+both	O
+archaeal	B-GENE
+and	I-GENE
+bacterial	I-GENE
+citrate	I-GENE
+synthases	I-GENE
+;	O
+PrpD	B-GENE
+showed	O
+homology	O
+to	O
+yeast	O
+and	O
+Bacillus	O
+subtilis	O
+proteins	O
+of	O
+unknown	O
+function	O
+;	O
+PrpE	B-GENE
+showed	O
+homology	O
+to	O
+acetyl	B-GENE
+coenzyme	I-GENE
+A	I-GENE
+synthetases	I-GENE
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURES	O
+:	O
+Systemic	O
+and	O
+pulmonary	O
+hemodynamics	O
+,	O
+arterial	O
+blood	O
+gas	O
+determination	O
+,	O
+bronchoalveolar	O
+lavage	O
+protein	O
+and	O
+neutrophil	O
+content	O
+,	O
+neutrophil	O
+oxidant	O
+burst	O
+,	O
+lung	B-GENE
+myeloperoxidase	I-GENE
+content	O
+,	O
+and	O
+scanning	O
+electron	O
+micrographic	O
+studies	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+cDNA	O
+encoding	O
+human	B-GENE
+MEKK3	I-GENE
+.	O
+
+To	O
+investigate	O
+the	O
+mechanisms	O
+involved	O
+in	O
+the	O
+transcriptional	O
+control	O
+of	O
+retinoid	B-GENE
+X	I-GENE
+receptor	I-GENE
+(	O
+RXR	B-GENE
+)	O
+gene	O
+expression	O
+,	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+RXRgamma2	I-GENE
+isoform	I-GENE
+was	O
+characterized	O
+.	O
+
+JNK	B-GENE
+and	O
+p38	B-GENE
+are	O
+constitutively	O
+present	O
+in	O
+the	O
+nucleus	O
+,	O
+and	O
+DNA	O
+-	O
+bound	O
+c	B-GENE
+-	I-GENE
+JUN	I-GENE
+and	O
+ATF	B-GENE
+-	I-GENE
+2	I-GENE
+are	O
+stably	O
+contacted	O
+by	O
+JNK	B-GENE
+and	O
+p38	B-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+effects	O
+of	O
+dominant	O
+interfering	O
+forms	O
+of	O
+the	O
+JNK	B-GENE
+/	O
+p38	B-GENE
+signaling	O
+pathway	O
+demonstrate	O
+that	O
+activation	O
+of	O
+these	O
+kinases	O
+is	O
+critical	O
+for	O
+cytokine	O
+-	O
+induced	O
+E	B-GENE
+-	I-GENE
+selectin	I-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Sp1	B-GENE
+binds	O
+the	O
+CTC	O
+repeat	O
+with	O
+an	O
+affinity	O
+,	O
+KD	O
+=	O
+0	O
+.	O
+37	O
+nM	O
+,	O
+at	O
+least	O
+as	O
+high	O
+as	O
+the	O
+consensus	O
+GC	O
+box	O
+.	O
+
+Identification	O
+of	O
+the	O
+region	O
+in	O
+actin	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+that	O
+binds	O
+to	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+glycoprotein	B-GENE
+IBalpha	I-GENE
+.	O
+
+Mutant	O
+enzyme	O
+forms	O
+were	O
+prepared	O
+to	O
+eliminate	O
+the	O
+initial	O
+autoprocessing	O
+site	O
+and	O
+thus	O
+form	O
+an	O
+active	O
+single	O
+-	O
+chain	O
+protein	O
+for	O
+structure	O
+-	O
+function	O
+studies	O
+.	O
+
+The	O
+primer	O
+is	O
+generated	O
+by	O
+a	O
+cleavage	O
+that	O
+occurs	O
+between	O
+bases	O
+11	O
+and	O
+12	O
+of	O
+the	O
+Tf1	B-GENE
+mRNA	I-GENE
+.	O
+
+Similarly	O
+,	O
+we	O
+examined	O
+whether	O
+the	O
+ELK1	B-GENE
+,	O
+SAP1a	B-GENE
+,	O
+FLI1	B-GENE
+,	O
+EWS	B-GENE
+-	O
+FLI1	B-GENE
+,	O
+ETS1	B-GENE
+,	O
+ETS2	B-GENE
+,	O
+PEA3	B-GENE
+and	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+proteins	I-GENE
+can	O
+form	O
+ternary	O
+complexes	O
+with	O
+SRF	B-GENE
+on	O
+the	O
+Egr1	B-GENE
+SREI	B-GENE
+and	I-GENE
+II	I-GENE
+.	O
+
+This	O
+R	O
+-	O
+domain	O
+may	O
+modulate	O
+the	O
+interaction	O
+with	O
+SRF	B-GENE
+,	O
+providing	O
+a	O
+mechanism	O
+that	O
+would	O
+be	O
+unique	O
+to	O
+FLI1	B-GENE
+and	O
+EWS	B-GENE
+-	O
+FLI1	B-GENE
+,	O
+thus	O
+implicating	O
+a	O
+novel	O
+function	O
+for	O
+these	O
+ETS	B-GENE
+transcription	I-GENE
+factors	I-GENE
+in	O
+the	O
+regulation	O
+of	O
+the	O
+Egr1	B-GENE
+gene	I-GENE
+.	O
+
+The	O
+murine	O
+chromosomal	O
+locations	O
+of	O
+the	O
+five	O
+NMDA	B-GENE
+receptor	I-GENE
+channel	I-GENE
+subunits	I-GENE
+,	O
+the	O
+epsilon	B-GENE
+1	I-GENE
+(	O
+Grin2a	B-GENE
+)	O
+,	O
+epsilon	B-GENE
+2	I-GENE
+(	O
+Grin2b	B-GENE
+)	O
+,	O
+epsilon	B-GENE
+3	I-GENE
+(	O
+Grin2c	B-GENE
+)	O
+,	O
+epsilon	B-GENE
+4	I-GENE
+(	O
+Grin2d	B-GENE
+)	O
+and	O
+zeta	B-GENE
+1	I-GENE
+(	O
+Grinl	B-GENE
+)	O
+subunits	O
+,	O
+were	O
+determined	O
+using	O
+an	O
+interspecific	O
+backcross	O
+mapping	O
+panel	O
+derived	O
+from	O
+crosses	O
+of	O
+[	O
+(	O
+C57BL	O
+/	O
+6JxM	O
+.	O
+spretus	O
+)	O
+F1xC57BL	O
+/	O
+6J	O
+]	O
+mice	O
+.	O
+
+CDNA	O
+cloning	O
+of	O
+chick	B-GENE
+brain	I-GENE
+alpha	I-GENE
+-	I-GENE
+amino	I-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+5	I-GENE
+-	I-GENE
+methyl	I-GENE
+-	I-GENE
+4	I-GENE
+-	I-GENE
+isoxazolepropionic	I-GENE
+acid	I-GENE
+receptors	I-GENE
+reveals	O
+conservation	O
+of	O
+structure	O
+,	O
+function	O
+and	O
+post	O
+-	O
+transcriptional	O
+processes	O
+with	O
+mammalian	O
+receptors	O
+.	O
+
+Remarkably	O
+,	O
+both	O
+TTD	O
+-	O
+A	O
+and	O
+XP	O
+-	O
+D	O
+defects	O
+are	O
+associated	O
+with	O
+subunits	O
+of	O
+TFIIH	B-GENE
+,	O
+a	O
+basal	O
+transcription	O
+factor	O
+with	O
+a	O
+second	O
+function	O
+in	O
+DNA	O
+repair	O
+.	O
+
+Adjustment	O
+for	O
+age	O
+,	O
+total	O
+cholesterol	O
+,	O
+HDL	B-GENE
+cholesterol	I-GENE
+,	O
+triglycerides	O
+,	O
+current	O
+smoking	O
+,	O
+and	O
+systolic	O
+pressure	O
+slightly	O
+reduced	O
+the	O
+association	O
+between	O
+fibrinogen	B-GENE
+and	O
+atherosclerosis	O
+.	O
+
+Cholesterol	B-GENE
+side	I-GENE
+-	I-GENE
+chain	I-GENE
+cleavage	I-GENE
+cytochrome	I-GENE
+P450	I-GENE
+(	O
+CYP11A	B-GENE
+;	O
+P450scc	B-GENE
+)	O
+gene	O
+expression	O
+is	O
+regulated	O
+by	O
+gonadotropins	B-GENE
+via	O
+cAMP	O
+in	O
+the	O
+ovary	O
+and	O
+by	O
+ACTH	B-GENE
+via	O
+cAMP	O
+in	O
+adrenal	O
+cortical	O
+cells	O
+.	O
+
+One	O
+possible	O
+solution	O
+is	O
+a	O
+thin	O
+radial	O
+forearm	O
+free	O
+flap	O
+.	O
+
+Structural	O
+analysis	O
+and	O
+characterization	O
+of	O
+tissue	O
+and	O
+hormonal	O
+responsive	O
+expression	O
+of	O
+the	O
+avian	B-GENE
+bone	I-GENE
+sialoprotein	I-GENE
+(	O
+BSP	B-GENE
+)	O
+gene	O
+.	O
+
+The	O
+Y	O
+-	O
+type	O
+structural	O
+motif	O
+is	O
+also	O
+conserved	O
+among	O
+a	O
+number	O
+of	O
+divergent	O
+BiP	B-GENE
+mRNAs	I-GENE
+.	O
+
+A	O
+false	O
+positive	O
+marker	O
+screen	O
+was	O
+associated	O
+with	O
+the	O
+occurrence	O
+of	O
+hand	O
+-	O
+foot	O
+syndrome	O
+even	O
+when	O
+the	O
+effect	O
+of	O
+regimen	O
+was	O
+accounted	O
+for	O
+by	O
+stratification	O
+(	O
+p	O
+=	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+detection	O
+of	O
+ORF	B-GENE
+-	I-GENE
+1	I-GENE
+sequences	O
+in	O
+human	O
+tumors	O
+,	O
+while	O
+not	O
+proof	O
+per	O
+se	O
+,	O
+is	O
+a	O
+prerequisite	O
+for	O
+establishing	O
+its	O
+role	O
+in	O
+tumor	O
+development	O
+.	O
+
+Phylogenetic	O
+analysis	O
+gave	O
+evidence	O
+for	O
+a	O
+close	O
+evolutionary	O
+relationship	O
+between	O
+PhHV	O
+-	O
+1	O
+and	O
+members	O
+of	O
+the	O
+Varicellovirus	O
+genus	O
+of	O
+the	O
+alpha	O
+-	O
+Herpesvirinae	O
+and	O
+canid	O
+herpesvirus	O
+in	O
+particular	O
+.	O
+
+In	O
+this	O
+method	O
+,	O
+PLP	O
+in	O
+plasma	O
+can	O
+be	O
+determined	O
+with	O
+high	O
+sensitivity	O
+using	O
+derivatization	O
+with	O
+sodium	O
+bisulfite	O
+in	O
+the	O
+mobile	O
+phase	O
+.	O
+
+Both	O
+HEF1	B-GENE
+and	O
+Cas	B-GENE
+were	O
+found	O
+to	O
+complex	O
+with	O
+the	O
+related	B-GENE
+adhesion	I-GENE
+focal	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+(	O
+RAFTK	B-GENE
+)	O
+,	O
+and	O
+when	O
+tyrosine	O
+phosphorylated	O
+,	O
+with	O
+the	O
+adapter	O
+molecule	O
+CrkL	B-GENE
+.	O
+
+SIM1	B-GENE
+and	O
+SIM2	B-GENE
+do	O
+not	O
+form	O
+homodimers	O
+,	O
+and	O
+they	O
+do	O
+not	O
+interact	O
+with	O
+AHR	B-GENE
+.	O
+
+Complexes	O
+of	O
+qTBP42	B-GENE
+with	O
+each	O
+complementary	O
+strand	O
+of	O
+telomeric	O
+DNA	O
+and	O
+with	O
+quadruplex	O
+forms	O
+of	O
+the	O
+guanine	O
+-	O
+rich	O
+strand	O
+had	O
+3	O
+.	O
+7	O
+-	O
+14	O
+.	O
+6	O
+nM	O
+dissociation	O
+constants	O
+,	O
+Kd	O
+,	O
+whereas	O
+complexes	O
+with	O
+double	O
+-	O
+stranded	O
+telomeric	O
+DNA	O
+had	O
+up	O
+to	O
+100	O
+-	O
+fold	O
+higher	O
+Kd	O
+values	O
+.	O
+
+Moreover	O
+,	O
+the	O
+effect	O
+exerted	O
+by	O
+TIS1	B-GENE
+appeared	O
+to	O
+be	O
+selective	O
+for	O
+the	O
+MCK	B-GENE
+promoter	I-GENE
+.	O
+
+What	O
+'	O
+s	O
+new	O
+in	O
+gynecologic	O
+and	O
+obstetrical	O
+surgery	O
+.	O
+
+The	O
+dnaK	B-GENE
+operon	I-GENE
+of	I-GENE
+Bacillus	I-GENE
+subtilis	I-GENE
+is	O
+heptacistronic	O
+.	O
+
+Moreover	O
+,	O
+expression	O
+of	O
+CBF1	B-GENE
+in	O
+yeast	O
+was	O
+found	O
+to	O
+activate	O
+transcription	O
+of	O
+reporter	O
+genes	O
+containing	O
+the	O
+C	O
+-	O
+repeat	O
+/	O
+DRE	O
+as	O
+an	O
+upstream	O
+activator	O
+sequence	O
+but	O
+not	O
+mutant	O
+versions	O
+of	O
+the	O
+DNA	O
+element	O
+.	O
+
+Forty	O
+-	O
+one	O
+ASA	O
+physical	O
+status	O
+I	O
+or	O
+II	O
+adult	O
+patients	O
+undergoing	O
+a	O
+variety	O
+of	O
+1	O
+-	O
+1	O
+.	O
+5	O
+h	O
+surgical	O
+procedures	O
+were	O
+randomly	O
+allocated	O
+to	O
+receive	O
+CCA	O
+with	O
+desflurane	O
+or	O
+isoflurane	O
+with	O
+ventilation	O
+being	O
+either	O
+spontaneous	O
+or	O
+controlled	O
+.	O
+
+OBJECTIVE	O
+:	O
+Our	O
+goal	O
+was	O
+to	O
+determine	O
+whether	O
+chlamydia	O
+-	O
+infected	O
+women	O
+have	O
+a	O
+higher	O
+rate	O
+of	O
+febrile	O
+complications	O
+after	O
+postpartum	O
+tubal	O
+ligation	O
+.	O
+
+In	O
+the	O
+electrophoresis	O
+mobility	O
+shift	O
+assay	O
+using	O
+nuclear	O
+extracts	O
+of	O
+the	O
+myogenic	O
+cells	O
+,	O
+MyoD	B-GENE
+and	O
+myogenin	B-GENE
+bound	O
+to	O
+the	O
+right	O
+E	O
+-	O
+box	O
+in	O
+the	O
+enhancer	O
+region	O
+of	O
+the	O
+MCK	B-GENE
+gene	I-GENE
+even	O
+in	O
+the	O
+presence	O
+of	O
+BMP	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+A	O
+heterologous	O
+promoter	O
+construct	O
+containing	O
+three	O
+repeats	O
+of	O
+a	O
+consensus	O
+Sp1	B-GENE
+site	I-GENE
+,	O
+cloned	O
+upstream	O
+of	O
+a	O
+single	O
+copy	O
+of	O
+the	O
+ZII	B-GENE
+(	O
+CREB	B-GENE
+/	I-GENE
+AP1	I-GENE
+)	O
+element	O
+from	O
+the	O
+BZLF1	B-GENE
+promoter	I-GENE
+linked	O
+to	O
+the	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+TATA	O
+box	O
+,	O
+exhibited	O
+phorbol	O
+ester	O
+inducibility	O
+.	O
+
+Subsequent	O
+experiments	O
+showed	O
+that	O
+motoric	O
+tasks	O
+rather	O
+than	O
+cognitive	O
+aspects	O
+of	O
+the	O
+COWA	O
+task	O
+were	O
+critical	O
+in	O
+potentiating	O
+finger	O
+-	O
+tapping	O
+performance	O
+.	O
+
+cDNA	O
+cloning	O
+,	O
+expression	O
+analysis	O
+,	O
+and	O
+chromosomal	O
+localization	O
+of	O
+a	O
+gene	O
+with	O
+high	O
+homology	O
+to	O
+wheat	B-GENE
+eIF	I-GENE
+-	I-GENE
+(	I-GENE
+iso	I-GENE
+)	I-GENE
+4F	I-GENE
+and	O
+mammalian	B-GENE
+eIF	I-GENE
+-	I-GENE
+4G	I-GENE
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+important	O
+to	O
+control	O
+hypertension	O
+and	O
+keep	O
+appropriate	O
+renal	O
+blood	O
+flow	O
+during	O
+living	O
+renal	O
+transplantation	O
+surgery	O
+.	O
+
+The	O
+initial	O
+patients	O
+treated	O
+with	O
+AZQ	O
+and	O
+mitroxantrone	O
+experienced	O
+prolonged	O
+bone	O
+marrow	O
+suppression	O
+and	O
+,	O
+therefore	O
+,	O
+subsequent	O
+cohorts	O
+were	O
+treated	O
+with	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+,	O
+5	O
+micrograms	O
+/	O
+kg	O
+,	O
+beginning	O
+the	O
+day	O
+after	O
+completion	O
+of	O
+the	O
+third	O
+cycle	O
+of	O
+chemotherapy	O
+.	O
+
+Human	B-GENE
+granulocyte	I-GENE
+-	I-GENE
+macrophage	I-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+hGM	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+activates	O
+a	O
+set	O
+of	O
+genes	O
+such	O
+as	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+,	O
+jun	B-GENE
+,	O
+myc	B-GENE
+,	O
+and	O
+early	B-GENE
+growth	I-GENE
+response	I-GENE
+gene	I-GENE
+1	I-GENE
+(	O
+egr	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+In	O
+order	O
+to	O
+provide	O
+adequate	O
+local	O
+control	O
+without	O
+compromising	O
+cosmetic	O
+outcome	O
+,	O
+the	O
+amount	O
+of	O
+breast	O
+tissue	O
+that	O
+must	O
+be	O
+excised	O
+in	O
+BCT	O
+needs	O
+to	O
+be	O
+individualized	O
+.	O
+
+Surprisingly	O
+,	O
+however	O
+,	O
+TCR	B-GENE
+-	O
+mediated	O
+tyrosine	O
+phosphorylation	O
+of	O
+phospholipase	B-GENE
+C	I-GENE
+gamma	I-GENE
+1	I-GENE
+remains	O
+intact	O
+in	O
+the	O
+Jurkat	O
+cells	O
+expressing	O
+the	O
+A2	B-GENE
+/	O
+HCP	B-GENE
+chimera	O
+.	O
+
+The	O
+14	B-GENE
+.	I-GENE
+1	I-GENE
+(	I-GENE
+IGLL1	I-GENE
+)	I-GENE
+gene	I-GENE
+is	O
+expressed	O
+in	O
+a	O
+lineage	O
+-	O
+and	O
+stage	O
+-	O
+restricted	O
+manner	O
+.	O
+
+The	O
+interferon	B-GENE
+(	O
+IFN	B-GENE
+)	O
+-	O
+induced	O
+double	B-GENE
+-	I-GENE
+stranded	I-GENE
+RNA	I-GENE
+(	I-GENE
+dsRNA	I-GENE
+)	I-GENE
+-	I-GENE
+activated	I-GENE
+Ser	I-GENE
+/	I-GENE
+Thr	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+PKR	B-GENE
+)	O
+plays	O
+a	O
+role	O
+in	O
+the	O
+antiviral	O
+and	O
+antiproliferative	O
+effects	O
+of	O
+IFN	B-GENE
+.	O
+
+Together	O
+,	O
+the	O
+data	O
+suggest	O
+that	O
+cAMP	O
+-	O
+dependent	O
+control	O
+of	O
+the	O
+amounts	O
+of	O
+the	O
+activator	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+vs	O
+.	O
+the	O
+repressor	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+could	O
+influence	O
+CRS2	O
+-	O
+dependent	O
+transcription	O
+.	O
+
+Object	O
+relations	O
+,	O
+affect	O
+management	O
+,	O
+and	O
+psychic	O
+structure	O
+formation	O
+.	O
+
+When	O
+expressed	O
+in	O
+COS	O
+-	O
+7	O
+cells	O
+,	O
+MKP	B-GENE
+-	I-GENE
+4	I-GENE
+blocks	O
+activation	O
+of	O
+MAP	B-GENE
+kinases	I-GENE
+with	O
+the	O
+selectivity	O
+ERK	B-GENE
+>	O
+p38	B-GENE
+=	O
+JNK	B-GENE
+/	O
+SAPK	B-GENE
+.	O
+
+Most	O
+kinases	O
+are	O
+not	O
+significantly	O
+inhibited	O
+by	O
+roscovitine	O
+.	O
+cdc2	B-GENE
+/	O
+cyclin	B-GENE
+B	I-GENE
+,	O
+cdk2	B-GENE
+/	O
+cyclin	B-GENE
+A	I-GENE
+,	O
+cdk2	B-GENE
+/	O
+cyclin	B-GENE
+E	I-GENE
+and	O
+cdk5	B-GENE
+/	O
+p35	B-GENE
+only	O
+are	O
+substantially	O
+inhibited	O
+(	O
+IC50	O
+values	O
+of	O
+0	O
+.	O
+65	O
+,	O
+0	O
+.	O
+7	O
+,	O
+0	O
+.	O
+7	O
+and	O
+0	O
+.	O
+2	O
+microM	O
+,	O
+respectively	O
+)	O
+.	O
+cdk4	B-GENE
+/	O
+cyclin	B-GENE
+D1	I-GENE
+and	O
+cdk6	B-GENE
+/	O
+cyclin	B-GENE
+D2	I-GENE
+are	O
+very	O
+poorly	O
+inhibited	O
+by	O
+roscovitine	O
+(	O
+IC50	O
+>	O
+100	O
+microM	O
+)	O
+.	O
+
+Interaction	O
+of	O
+Ets	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+the	O
+POU	B-GENE
+-	I-GENE
+homeodomain	I-GENE
+protein	I-GENE
+GHF	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+reconstitutes	O
+pituitary	O
+-	O
+specific	O
+gene	O
+expression	O
+.	O
+
+Although	O
+Pho85	B-GENE
+is	O
+not	O
+essential	O
+for	O
+viability	O
+,	O
+Pcl1	B-GENE
+,	I-GENE
+2	I-GENE
+-	O
+Pho85	B-GENE
+kinase	O
+complexes	O
+become	O
+essential	O
+for	O
+Start	O
+in	O
+the	O
+absence	O
+of	O
+Cln1	B-GENE
+,	I-GENE
+2	I-GENE
+-	O
+Cdc28	B-GENE
+kinases	O
+.	O
+
+Using	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+to	O
+screen	O
+for	O
+proteins	O
+which	O
+interact	O
+with	O
+Tax1	B-GENE
+,	O
+we	O
+isolated	O
+the	O
+B	O
+subunit	O
+of	O
+the	O
+CCAAT	O
+binding	O
+protein	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+from	O
+a	O
+HeLa	O
+cDNA	O
+library	O
+.	O
+
+Enhancer	O
+activity	O
+requires	O
+both	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+and	O
+these	O
+adjacent	O
+sequences	O
+.	O
+
+Studies	O
+using	O
+HLA	B-GENE
+-	I-GENE
+DR	I-GENE
+-	O
+B7	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+LFA	B-GENE
+-	I-GENE
+3	I-GENE
+triple	O
+transfectants	O
+showed	O
+that	O
+the	O
+LFA	B-GENE
+-	I-GENE
+3	I-GENE
+-	O
+induced	O
+NF	B-GENE
+-	I-GENE
+AT	I-GENE
+DNA	O
+binding	O
+activity	O
+was	O
+negatively	O
+regulated	O
+by	O
+B7	B-GENE
+-	I-GENE
+1	I-GENE
+costimulation	O
+.	O
+
+Constitutive	O
+activation	O
+of	O
+Rac1	B-GENE
+and	O
+RhoA	B-GENE
+causes	O
+tumorigenic	O
+transformation	O
+of	O
+NIH	O
+3T3	O
+cells	O
+,	O
+and	O
+their	O
+functions	O
+may	O
+be	O
+required	O
+for	O
+full	O
+Ras	B-GENE
+transformation	O
+.	O
+
+Furthermore	O
+,	O
+Rac1	B-GENE
+activation	O
+of	O
+JNK	B-GENE
+or	O
+SRF	B-GENE
+,	O
+or	O
+induction	O
+of	O
+lamellipodia	O
+,	O
+was	O
+neither	O
+necessary	O
+nor	O
+sufficient	O
+for	O
+Rac1	B-GENE
+transforming	O
+activity	O
+.	O
+
+Overexpression	O
+of	O
+the	O
+bZip	O
+interaction	O
+domain	O
+of	O
+CBP	B-GENE
+specifically	O
+abolishes	O
+the	O
+positive	O
+cross	O
+talk	O
+between	O
+TR	B-GENE
+and	O
+p45	B-GENE
+/	O
+NF	B-GENE
+-	I-GENE
+E2	I-GENE
+.	O
+
+This	O
+inhibitory	O
+domain	O
+has	O
+been	O
+deleted	O
+in	O
+all	O
+naturally	O
+occurring	O
+AHC	B-GENE
+deletion	I-GENE
+mutants	I-GENE
+described	O
+to	O
+date	O
+.	O
+
+Identification	O
+of	O
+a	O
+promoter	O
+-	O
+specific	O
+transactivation	O
+domain	O
+in	O
+the	O
+herpes	B-GENE
+simplex	I-GENE
+virus	I-GENE
+regulatory	I-GENE
+protein	I-GENE
+ICP4	I-GENE
+.	O
+
+DNA	O
+sequencing	O
+of	O
+a	O
+17	O
+-	O
+kb	O
+segment	O
+encompassing	O
+a	O
+gammaherpesvirus	O
+divergent	O
+locus	O
+(	O
+DL	O
+-	O
+B	O
+)	O
+between	O
+ORF11	O
+and	O
+ORF17	O
+revealed	O
+the	O
+presence	O
+of	O
+nine	O
+viral	O
+ORFs	O
+with	O
+predicted	O
+gene	O
+products	O
+related	O
+to	O
+cellular	O
+proteins	O
+.	O
+
+Studies	O
+in	O
+mammalian	O
+cells	O
+have	O
+correlated	O
+induction	O
+of	O
+inhibitory	O
+tyrosine	O
+15	O
+(	O
+Y15	O
+)	O
+phosphorylation	O
+on	O
+p34cdc2	B-GENE
+with	O
+the	O
+response	O
+to	O
+DNA	O
+damage	O
+.	O
+
+We	O
+report	O
+herein	O
+the	O
+case	O
+of	O
+a	O
+30	O
+-	O
+year	O
+-	O
+old	O
+man	O
+in	O
+whom	O
+ectopic	O
+mediastinal	O
+parathyroid	O
+adenoma	O
+was	O
+detected	O
+by	O
+99mTc	O
+-	O
+methoxyisobutylisonitrile	O
+scintigraphy	O
+(	O
+99mTc	O
+-	O
+MIBI	O
+)	O
+.	O
+
+Cardiac	B-GENE
+endothelin	I-GENE
+release	O
+and	O
+infarct	O
+size	O
+,	O
+myocardial	O
+blood	O
+flow	O
+,	O
+and	O
+ventricular	O
+function	O
+in	O
+canine	O
+infarction	O
+and	O
+reperfusion	O
+.	O
+
+The	O
+workup	O
+included	O
+skin	O
+tests	O
+(	O
+up	O
+to	O
+1	O
+microgram	O
+/	O
+ml	O
+,	O
+Pharmacia	O
+)	O
+,	O
+measurement	O
+of	O
+specific	O
+serum	O
+IgE	B-GENE
+with	O
+RAST	O
+-	O
+CAP	O
+(	O
+Pharmacia	O
+)	O
+,	O
+and	O
+CAST	O
+with	O
+three	O
+concentrations	O
+of	O
+bee	O
+(	O
+Apis	O
+mellifera	O
+)	O
+and	O
+wasp	O
+(	O
+Vespula	O
+spec	O
+.	O
+)	O
+venom	O
+(	O
+Aquagen	O
+ALK	O
+)	O
+.	O
+
+The	O
+proliferation	B-GENE
+potential	I-GENE
+protein	I-GENE
+-	I-GENE
+related	I-GENE
+(	O
+P2P	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+gene	O
+with	O
+domains	O
+encoding	O
+heterogeneous	O
+nuclear	O
+ribonucleoprotein	O
+association	O
+and	O
+Rb1	B-GENE
+binding	O
+shows	O
+repressed	O
+expression	O
+during	O
+terminal	O
+differentiation	O
+.	O
+
+Recent	O
+application	O
+of	O
+recombinant	O
+canarypox	O
+ALVAC	O
+/	O
+HIV	O
+-	O
+1	O
+vectors	O
+as	O
+vaccine	O
+immunogens	O
+in	O
+HIV	O
+-	O
+1	O
+,	O
+-	O
+noninfected	O
+volunteers	O
+has	O
+produced	O
+CTL	O
+responses	O
+in	O
+a	O
+significant	O
+number	O
+of	O
+vaccinees	O
+.	O
+
+The	O
+relevance	O
+of	O
+these	O
+elements	O
+in	O
+conferring	O
+anaerobic	O
+induction	O
+of	O
+gpc4	B-GENE
+gene	I-GENE
+expression	O
+is	O
+discussed	O
+.	O
+
+Exons	O
+A1a	O
+and	O
+A1b	O
+are	O
+separated	O
+from	O
+each	O
+other	O
+by	O
+a	O
+124	O
+-	O
+nucleotide	O
+intron	O
+.	O
+
+A	O
+MEK	B-GENE
+-	O
+specific	O
+inhibitor	O
+(	O
+PD098059	O
+)	O
+(	O
+Dudley	O
+,	O
+D	O
+.	O
+
+These	O
+data	O
+support	O
+the	O
+idea	O
+that	O
+the	O
+repression	O
+activity	O
+of	O
+NRSF	B-GENE
+/	O
+REST	B-GENE
+depends	O
+upon	O
+the	O
+species	O
+of	O
+promoter	O
+to	O
+which	O
+it	O
+is	O
+linked	O
+and	O
+upon	O
+the	O
+proteins	O
+that	O
+bind	O
+to	O
+those	O
+promoters	O
+.	O
+
+Enhanced	O
+period	O
+-	O
+peak	O
+analysis	O
+of	O
+electro	O
+-	O
+encephalograms	O
+using	O
+a	O
+fast	O
+sinc	O
+function	O
+.	O
+
+In	O
+summary	O
+,	O
+p56	B-GENE
+(	O
+lck	B-GENE
+)	O
+activity	O
+stimulates	O
+G1	O
+/	O
+S	O
+transition	O
+in	O
+immature	O
+thymoblasts	O
+and	O
+maintains	O
+cell	O
+viability	O
+via	O
+transduction	O
+of	O
+constitutive	O
+activation	O
+signals	O
+downstream	O
+to	O
+components	O
+of	O
+the	O
+Ras	B-GENE
+/	O
+Raf	B-GENE
+/	O
+MAPK	B-GENE
+pathway	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+intraarterial	O
+neoadjuvant	O
+chemotherapy	O
+should	O
+be	O
+effective	O
+on	O
+advanced	O
+cervical	O
+cancer	O
+.	O
+
+The	O
+FBF	O
+questionnaire	O
+did	O
+not	O
+highlight	O
+a	O
+characteristic	O
+basic	O
+symptoms	O
+profile	O
+of	O
+schizoaffective	O
+disorder	O
+,	O
+when	O
+compared	O
+with	O
+bipolar	O
+affective	O
+disorder	O
+and	O
+schizophrenia	O
+.	O
+
+The	O
+alternative	O
+sigma	B-GENE
+factor	I-GENE
+sigmaB	I-GENE
+in	I-GENE
+Staphylococcus	I-GENE
+aureus	I-GENE
+:	O
+regulation	O
+of	O
+the	O
+sigB	B-GENE
+operon	I-GENE
+in	O
+response	O
+to	O
+growth	O
+phase	O
+and	O
+heat	O
+shock	O
+
+Cognate	O
+promoter	O
+elements	O
+implicated	O
+in	O
+glucocorticoid	O
+-	O
+and	O
+cAMP	O
+-	O
+mediated	O
+regulation	O
+as	O
+well	O
+as	O
+in	O
+liver	O
+-	O
+,	O
+myeloid	O
+-	O
+,	O
+and	O
+lymphocyte	O
+-	O
+specific	O
+expression	O
+are	O
+located	O
+within	O
+the	O
+5	O
+'	O
+flanking	O
+sequence	O
+.	O
+
+We	O
+have	O
+studied	O
+the	O
+biokinetics	O
+of	O
+BLM	O
+labeled	O
+with	O
+indium	O
+-	O
+111	O
+(	O
+In	O
+-	O
+111	O
+)	O
+.	O
+
+CD3	B-GENE
+cross	O
+-	O
+linking	O
+induced	O
+tyrosine	O
+phosphorylation	O
+of	O
+Sam68	B-GENE
+in	O
+uninfected	O
+T	O
+cells	O
+.	O
+
+Acetoin	O
+-	O
+dependent	O
+expression	O
+of	O
+the	O
+acoABCD	B-GENE
+operon	I-GENE
+could	O
+be	O
+restored	O
+in	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+acoK	I-GENE
+mutants	I-GENE
+by	O
+supplying	O
+a	O
+plasmid	O
+carrying	O
+an	O
+intact	O
+acoK	B-GENE
+,	O
+suggesting	O
+a	O
+transactivating	O
+function	O
+of	O
+the	O
+gene	O
+product	O
+.	O
+
+Mutations	O
+in	O
+the	O
+alpha	B-GENE
+and	I-GENE
+sigma	I-GENE
+-	I-GENE
+70	I-GENE
+subunits	I-GENE
+of	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+affect	O
+expression	O
+of	O
+the	O
+mer	B-GENE
+operon	I-GENE
+.	O
+
+Taken	O
+together	O
+,	O
+we	O
+provide	O
+evidence	O
+for	O
+the	O
+existence	O
+of	O
+an	O
+activator	O
+,	O
+NFE	B-GENE
+,	O
+which	O
+in	O
+combination	O
+with	O
+the	O
+p50	B-GENE
+and	O
+c	B-GENE
+-	I-GENE
+Rel	I-GENE
+proteins	I-GENE
+,	O
+are	O
+part	O
+of	O
+the	O
+transcription	O
+factor	O
+machinery	O
+that	O
+regulates	O
+3	O
+'	O
+enhancer	O
+activity	O
+,	O
+and	O
+thus	O
+the	O
+control	O
+of	O
+the	O
+IgH	B-GENE
+locus	I-GENE
+in	O
+late	O
+B	O
+lymphocyte	O
+development	O
+.	O
+
+The	O
+neuroprotective	O
+efficacy	O
+of	O
+the	O
+selective	O
+N	O
+-	O
+type	O
+voltage	O
+-	O
+sensitive	O
+calcium	O
+channel	O
+blocker	O
+,	O
+SNX	O
+-	O
+111	O
+,	O
+was	O
+evaluated	O
+in	O
+spontaneously	O
+hypertensive	O
+rats	O
+subjected	O
+to	O
+60	O
+min	O
+of	O
+focal	O
+cerebral	O
+ischemia	O
+by	O
+permanent	O
+ligation	O
+of	O
+the	O
+right	O
+common	O
+carotid	O
+artery	O
+and	O
+temporary	O
+occlusion	O
+of	O
+the	O
+right	O
+middle	O
+cerebral	O
+artery	O
+.	O
+
+The	O
+genes	O
+encoding	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+yTAFII60	I-GENE
+,	O
+the	O
+G4p1	B-GENE
+protein	I-GENE
+and	O
+a	O
+putative	O
+glucose	O
+transporter	O
+are	O
+contained	O
+in	O
+a	O
+12	O
+.	O
+3	O
+kb	O
+DNA	O
+fragment	O
+on	O
+the	O
+left	O
+arm	O
+of	O
+Saccharomyces	O
+cerevisiae	O
+chromosome	O
+VII	O
+.	O
+
+The	O
+protector	O
+doubled	O
+the	O
+estimated	O
+fall	O
+distance	O
+for	O
+fracture	O
+of	O
+the	O
+trochanter	O
+.	O
+
+Marinol	O
+/	O
+marijuana	O
+usage	O
+was	O
+associated	O
+with	O
+depressed	O
+CD4	B-GENE
++	I-GENE
+counts	O
+and	O
+elevated	O
+amylase	B-GENE
+levels	O
+within	O
+the	O
+DDI	O
+subgroup	O
+.	O
+
+METHODS	O
+:	O
+Fifty	O
+-	O
+eight	O
+patients	O
+who	O
+underwent	O
+a	O
+curative	O
+hepatic	O
+resection	O
+for	O
+HCC	O
+and	O
+whose	O
+preoperative	O
+AFP	B-GENE
+levels	O
+were	O
+>	O
+100	O
+ng	O
+/	O
+ml	O
+,	O
+were	O
+selected	O
+for	O
+this	O
+study	O
+.	O
+
+Calmodulin	B-GENE
+-	I-GENE
+binding	I-GENE
+peptide	I-GENE
+(	O
+CBP	B-GENE
+)	O
+,	O
+a	O
+peptide	O
+of	O
+26	O
+amino	O
+acids	O
+derived	O
+from	O
+muscle	B-GENE
+myosin	I-GENE
+light	I-GENE
+chain	I-GENE
+kinase	I-GENE
+(	O
+MLCK	B-GENE
+)	O
+,	O
+binds	O
+to	O
+calmodulin	B-GENE
+with	O
+nanomolar	O
+affinity	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+the	O
+type	O
+of	O
+tyrosine	B-GENE
+kinase	I-GENE
+receptor	I-GENE
+stimulated	O
+also	O
+participates	O
+in	O
+the	O
+nature	O
+of	O
+the	O
+cAMP	O
+effect	O
+.	O
+
+To	O
+gain	O
+insight	O
+into	O
+the	O
+possible	O
+involvement	O
+of	O
+p21	B-GENE
+in	O
+liver	O
+cell	O
+growth	O
+,	O
+the	O
+expression	O
+and	O
+regulation	O
+of	O
+the	O
+p21	B-GENE
+gene	I-GENE
+was	O
+evaluated	O
+in	O
+rodent	O
+models	O
+of	O
+liver	O
+regeneration	O
+and	O
+specimens	O
+of	O
+human	O
+liver	O
+diseases	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+of	O
+LeMT	B-GENE
+(	I-GENE
+A	I-GENE
+)	I-GENE
+and	O
+LeMT	B-GENE
+(	I-GENE
+B	I-GENE
+)	I-GENE
+showed	O
+that	O
+transcripts	O
+of	O
+both	O
+MT	B-GENE
+-	I-GENE
+like	I-GENE
+genes	I-GENE
+were	O
+more	O
+abundant	O
+in	O
+leaves	O
+than	O
+roots	O
+in	O
+tomato	O
+plants	O
+grown	O
+without	O
+addition	O
+of	O
+extra	O
+metal	O
+ions	O
+,	O
+a	O
+characteristic	O
+of	O
+type	B-GENE
+II	I-GENE
+MTs	I-GENE
+.	O
+
+The	O
+HBP	B-GENE
+gene	I-GENE
+is	O
+composed	O
+of	O
+eight	O
+exons	O
+covering	O
+19	O
+.	O
+5	O
+kb	O
+on	O
+the	O
+short	O
+arm	O
+of	O
+chromosome	O
+4	O
+.	O
+
+In	O
+some	O
+instances	O
+,	O
+this	O
+is	O
+partly	O
+mediated	O
+by	O
+the	O
+expression	O
+of	O
+virally	O
+encoded	O
+proteases	O
+which	O
+lead	O
+to	O
+the	O
+cleavage	O
+of	O
+initiation	B-GENE
+factor	I-GENE
+eIF4G	I-GENE
+.	O
+
+The	O
+best	O
+endometrial	O
+ablation	O
+was	O
+seen	O
+when	O
+SnET2	O
+was	O
+given	O
+by	O
+intrauterine	O
+administration	O
+with	O
+light	O
+treatment	O
+at	O
+150	O
+J	O
+/	O
+cm	O
+24	O
+hours	O
+later	O
+.	O
+
+Unlike	O
+class	O
+II	O
+-	O
+and	O
+III	O
+-	O
+specific	O
+TBP	B-GENE
+-	O
+TAF	B-GENE
+complexes	O
+,	O
+the	O
+corresponding	O
+murine	O
+and	O
+human	O
+class	O
+I	O
+-	O
+specific	O
+transcription	O
+initiation	O
+factor	O
+TIF	B-GENE
+-	I-GENE
+IB	I-GENE
+/	O
+SL1	B-GENE
+exhibits	O
+a	O
+pronounced	O
+selectivity	O
+for	O
+its	O
+homologous	O
+promoter	O
+.	O
+
+We	O
+now	O
+describe	O
+the	O
+identification	O
+of	O
+DEK	B-GENE
+as	O
+this	O
+43	B-GENE
+-	I-GENE
+kDa	I-GENE
+pets	I-GENE
+factor	I-GENE
+.	O
+
+These	O
+elements	O
+comprise	O
+a	O
+binding	O
+site	O
+for	O
+Krox	B-GENE
+proteins	I-GENE
+,	O
+one	O
+for	O
+nuclear	B-GENE
+factor	I-GENE
+1	I-GENE
+,	O
+an	O
+octamer	O
+motif	O
+that	O
+binds	O
+POU	B-GENE
+-	I-GENE
+homeodomain	I-GENE
+proteins	I-GENE
+,	O
+and	O
+a	O
+novel	O
+TN	B-GENE
+control	I-GENE
+element	I-GENE
+.	O
+
+Tissue	O
+samples	O
+were	O
+obtained	O
+either	O
+from	O
+rats	O
+that	O
+had	O
+been	O
+exposed	O
+to	O
+opiate	O
+withdrawal	O
+following	O
+a	O
+seven	O
+day	O
+morphine	O
+infusion	O
+or	O
+sham	O
+treated	O
+control	O
+subjects	O
+.	O
+
+Therefore	O
+,	O
+the	O
+impaired	O
+floor	O
+plate	O
+development	O
+in	O
+oep	B-GENE
+mutants	I-GENE
+is	O
+not	O
+caused	O
+by	O
+the	O
+absence	O
+of	O
+the	O
+floor	B-GENE
+plate	I-GENE
+inducer	I-GENE
+shh	I-GENE
+.	O
+
+RESULTS	O
+:	O
+The	O
+medians	O
+of	O
+average	O
+daily	O
+CD34	B-GENE
++	I-GENE
+cell	O
+yields	O
+for	O
+patients	O
+who	O
+received	O
+paclitaxel	O
+plus	O
+CY	O
+,	O
+CE	O
+,	O
+and	O
+CEP	O
+with	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+were	O
+12	O
+.	O
+9	O
+,	O
+11	O
+.	O
+03	O
+,	O
+and	O
+5	O
+.	O
+37	O
+x	O
+10	O
+(	O
+6	O
+)	O
+/	O
+kg	O
+,	O
+respectively	O
+,	O
+compared	O
+with	O
+2	O
+.	O
+02	O
+x	O
+10	O
+(	O
+6	O
+)	O
+/	O
+kg	O
+in	O
+the	O
+reference	O
+group	O
+that	O
+received	O
+CY	O
+with	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+(	O
+P	O
+=	O
+<	O
+.	O
+0001	O
+,	O
+.	O
+002	O
+,	O
+and	O
+.	O
+09	O
+,	O
+respectively	O
+)	O
+.	O
+
+Increased	O
+p53	B-GENE
+activity	O
+induced	O
+by	O
+OP	O
+is	O
+not	O
+due	O
+to	O
+elevated	O
+p53	B-GENE
+mRNA	I-GENE
+nor	O
+to	O
+protein	O
+levels	O
+.	O
+
+CONCLUSION	O
+:	O
+Chronic	O
+administration	O
+of	O
+misoprostol	O
+may	O
+have	O
+caused	O
+a	O
+negative	O
+natriuretic	O
+effect	O
+in	O
+cirrhotic	O
+patients	O
+with	O
+ascites	O
+.	O
+
+The	O
+intensity	O
+of	O
+the	O
+SSTEs	O
+is	O
+an	O
+order	O
+of	O
+magnitude	O
+larger	O
+than	O
+that	O
+of	O
+the	O
+MSEs	O
+and	O
+determines	O
+the	O
+signal	O
+contrast	O
+if	O
+both	O
+effects	O
+are	O
+selected	O
+simultaneously	O
+.	O
+
+In	O
+eukaryotic	O
+cells	O
+,	O
+premature	O
+termination	O
+of	O
+translation	O
+at	O
+nonsense	O
+codons	O
+has	O
+been	O
+implicated	O
+as	O
+the	O
+cause	O
+of	O
+a	O
+variety	O
+of	O
+posttranscriptional	O
+events	O
+,	O
+including	O
+rapid	O
+mRNA	O
+decay	O
+in	O
+the	O
+cytoplasm	O
+or	O
+the	O
+nucleus	O
+,	O
+altered	O
+splice	O
+site	O
+selection	O
+,	O
+and	O
+exon	O
+skipping	O
+.	O
+
+The	O
+region	O
+of	O
+plasmid	O
+pCM2	O
+encoding	O
+the	O
+pathogenicity	B-GENE
+locus	I-GENE
+pat	I-GENE
+-	I-GENE
+1	I-GENE
+was	O
+mapped	O
+by	O
+deletion	O
+analysis	O
+and	O
+complementation	O
+studies	O
+to	O
+a	O
+1	O
+.	O
+5	O
+-	O
+kb	O
+Bg	B-GENE
+/	I-GENE
+II	I-GENE
+/	O
+SmaI	B-GENE
+DNA	O
+fragment	O
+.	O
+
+Transient	O
+cotransfection	O
+of	O
+tat	B-GENE
+cDNA	I-GENE
+in	O
+sense	O
+orientation	O
+(	O
+tat	B-GENE
+/	I-GENE
+S	I-GENE
+)	O
+,	O
+together	O
+with	O
+a	O
+plasmid	O
+containing	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+promoter	I-GENE
+(	O
+FC3	B-GENE
+,	O
+from	O
+-	O
+711	O
+to	O
++	O
+42	O
+)	O
+in	O
+front	O
+of	O
+the	O
+bacterial	B-GENE
+chloramphenicol	I-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+gene	O
+significantly	O
+enhanced	O
+CAT	B-GENE
+activity	O
+in	O
+Jurkat	O
+cells	O
+activated	O
+by	O
+the	O
+addition	O
+of	O
+15	O
+%	O
+fetal	O
+calf	O
+serum	O
+(	O
+FCS	O
+)	O
+or	O
+5	O
+micrograms	O
+/	O
+mL	O
+phytohemagglutinin	B-GENE
+plus	O
+10	O
+(	O
+-	O
+7	O
+)	O
+mol	O
+/	O
+L	O
+phorbol	O
+myristate	O
+acetate	O
+(	O
+PMA	O
+)	O
+and	O
+U937	O
+cells	O
+activated	O
+by	O
+15	O
+%	O
+FCS	O
+or	O
+10	O
+(	O
+-	O
+7	O
+)	O
+mol	O
+/	O
+L	O
+PMA	O
+.	O
+
+Snail	O
+mortality	O
+did	O
+not	O
+differ	O
+among	O
+the	O
+various	O
+treatment	O
+conditions	O
+.	O
+
+Exploratory	O
+-	O
+motor	O
+task	O
+to	O
+evaluate	O
+right	O
+frontal	O
+lobe	O
+damage	O
+.	O
+
+To	O
+avoid	O
+complications	O
+,	O
+accurate	O
+quantitative	O
+analysis	O
+of	O
+NO	O
+and	O
+NO2	O
+is	O
+necessary	O
+during	O
+this	O
+therapy	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+that	O
+cis	O
+elements	O
+positioned	O
+between	O
+the	O
+alpha	B-GENE
+3	I-GENE
+and	O
+beta	B-GENE
+4	I-GENE
+coding	O
+regions	O
+are	O
+important	O
+for	O
+establishing	O
+part	O
+of	O
+the	O
+restricted	O
+CNS	O
+patterns	O
+of	O
+beta	B-GENE
+4	I-GENE
+,	O
+alpha	B-GENE
+3	I-GENE
+,	O
+and	O
+alpha	B-GENE
+5	I-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+RNase	B-GENE
+protection	O
+experiments	O
+confirmed	O
+the	O
+presence	O
+of	O
+the	O
+GHR1	B-GENE
+-	I-GENE
+279	I-GENE
+variant	I-GENE
+in	O
+IM	O
+-	O
+9	O
+cells	O
+and	O
+human	O
+liver	O
+.	O
+
+Functional	O
+tests	O
+using	O
+a	O
+reporter	O
+gene	O
+,	O
+containing	O
+Stat5	B-GENE
+-	I-GENE
+binding	I-GENE
+elements	I-GENE
+,	O
+confirmed	O
+that	O
+while	O
+the	O
+variant	O
+form	O
+was	O
+inactive	O
+by	O
+itself	O
+,	O
+it	O
+could	O
+inhibit	O
+the	O
+function	O
+of	O
+the	O
+full	O
+-	O
+length	O
+receptor	O
+.	O
+
+Conversely	O
+,	O
+activated	O
+glucocorticoid	B-GENE
+receptors	I-GENE
+suppressed	O
+the	O
+transactivation	O
+function	O
+of	O
+p53	B-GENE
+,	O
+while	O
+transrepression	O
+by	O
+p53	B-GENE
+was	O
+largely	O
+unaffected	O
+.	O
+
+This	O
+promoter	O
+segment	O
+could	O
+drive	O
+expression	O
+of	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+,	O
+could	O
+confer	O
+correct	O
+transcriptional	O
+initiation	O
+to	O
+the	O
+reporter	O
+and	O
+could	O
+confer	O
+the	O
+EGF	B-GENE
+-	O
+responsiveness	O
+previously	O
+observed	O
+in	O
+the	O
+native	O
+gene	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+report	O
+that	O
+an	O
+in	O
+vitro	O
+-	O
+synthesized	O
+alphavirus	O
+RNA	O
+lacking	O
+a	O
+poly	O
+(	O
+A	O
+)	O
+tail	O
+can	O
+initiate	O
+infection	O
+and	O
+produce	O
+3	O
+'	O
+polyadenylated	O
+viral	O
+genome	O
+in	O
+vivo	O
+.	O
+
+The	O
+human	O
+coreceptor	O
+was	O
+as	O
+active	O
+as	O
+the	O
+simian	O
+for	O
+SIV	O
+entry	O
+.	O
+
+RESULTS	O
+:	O
+Among	O
+women	O
+,	O
+the	O
+age	O
+-	O
+related	O
+decline	O
+in	O
+BMD	O
+at	O
+all	O
+non	O
+-	O
+spine	O
+skeletal	O
+sites	O
+was	O
+significantly	O
+different	O
+from	O
+zero	O
+,	O
+with	O
+the	O
+largest	O
+decline	O
+seen	O
+at	O
+the	O
+femoral	O
+neck	O
+(	O
+-	O
+.	O
+0038	O
+g	O
+/	O
+cm2	O
+/	O
+y	O
+,	O
+p	O
+<	O
+.	O
+001	O
+)	O
+and	O
+the	O
+smallest	O
+at	O
+the	O
+trochanter	O
+of	O
+the	O
+hip	O
+(	O
+-	O
+.	O
+0023	O
+g	O
+/	O
+cm2	O
+/	O
+y	O
+,	O
+p	O
+=	O
+.	O
+03	O
+)	O
+.	O
+
+Sixty	O
+-	O
+nine	O
+(	O
+44	O
+%	O
+)	O
+patients	O
+were	O
+administered	O
+250	O
+MBq	O
+(	O
+7	O
+mCi	O
+)	O
+99Tcm	O
+-	O
+tetrofosmin	O
+at	O
+rest	O
+followed	O
+4	O
+h	O
+later	O
+by	O
+750	O
+MBq	O
+(	O
+21	O
+mCi	O
+)	O
+during	O
+stress	O
+(	O
+the	O
+1	O
+day	O
+protocol	O
+)	O
+,	O
+whereas	O
+88	O
+(	O
+56	O
+%	O
+)	O
+patients	O
+had	O
+rest	O
+and	O
+stress	O
+imaging	O
+studies	O
+on	O
+two	O
+separate	O
+days	O
+,	O
+receiving	O
+a	O
+500	O
+MBq	O
+(	O
+14	O
+mCi	O
+)	O
+dose	O
+of	O
+99Tcm	O
+-	O
+tetrofosmin	O
+on	O
+each	O
+occasion	O
+(	O
+the	O
+2	O
+day	O
+protocol	O
+)	O
+.	O
+
+Myocardial	O
+SPET	O
+imaging	O
+with	O
+99Tcm	O
+-	O
+tetrofosmin	O
+in	O
+clinical	O
+practice	O
+:	O
+comparison	O
+of	O
+a	O
+1	O
+day	O
+and	O
+a	O
+2	O
+day	O
+imaging	O
+protocol	O
+.	O
+
+99Tcm	O
+-	O
+DMP	O
+-	O
+HSA	O
+showed	O
+an	O
+almost	O
+identical	O
+behaviour	O
+to	O
+in	O
+vitro	O
+labelled	O
+red	O
+blood	O
+cells	O
+(	O
+RBCs	O
+)	O
+,	O
+which	O
+are	O
+generally	O
+considered	O
+the	O
+reference	O
+standard	O
+for	O
+blood	O
+pool	O
+agents	O
+.	O
+
+Relief	O
+from	O
+autoinhibition	O
+and	O
+a	O
+subsequent	O
+10	O
+-	O
+60	O
+-	O
+fold	O
+increase	O
+in	O
+V	O
+(	O
+max	O
+)	O
+have	O
+been	O
+observed	O
+upon	O
+N	B-GENE
+-	I-GENE
+SH2	I-GENE
+domain	I-GENE
+engagement	O
+by	O
+a	O
+specific	O
+phosphotyrosyl	O
+ligand	O
+or	O
+upon	O
+deletion	O
+of	O
+the	O
+SH2	B-GENE
+domains	I-GENE
+to	O
+yield	O
+the	O
+catalytic	O
+PTPase	B-GENE
+domain	I-GENE
+.	O
+
+We	O
+have	O
+thus	O
+identified	O
+the	O
+first	O
+mammalian	B-GENE
+homolog	I-GENE
+of	I-GENE
+yeast	I-GENE
+UPF1	I-GENE
+,	O
+a	O
+protein	O
+that	O
+regulates	O
+levels	O
+of	O
+nonsense	O
+mRNA	O
+,	O
+and	O
+we	O
+tentatively	O
+name	O
+this	O
+protein	O
+human	B-GENE
+HUPF1	I-GENE
+(	O
+for	O
+human	B-GENE
+homolog	I-GENE
+of	I-GENE
+UPF1	I-GENE
+)	O
+.	O
+
+A	O
+miracle	O
+cure	O
+and	O
+its	O
+solution	O
+
+The	O
+addition	O
+of	O
+zidovudine	O
+did	O
+not	O
+influence	O
+this	O
+transfer	O
+.	O
+
+DNA	O
+strand	O
+exchange	O
+catalyzed	O
+by	O
+Rad51	B-GENE
+protein	I-GENE
+is	O
+also	O
+greatly	O
+stimulated	O
+by	O
+RPA	B-GENE
+.	O
+
+Ume6p	B-GENE
+,	O
+which	O
+also	O
+controls	O
+the	O
+expression	O
+of	O
+early	O
+meiotic	O
+genes	O
+,	O
+represses	O
+CAR1	B-GENE
+expression	O
+through	O
+a	O
+sequence	O
+called	O
+URS	O
+,	O
+as	O
+a	O
+function	O
+of	O
+nitrogen	O
+availability	O
+.	O
+
+The	O
+second	O
+class	O
+of	O
+cDNA	O
+hybridized	O
+to	O
+a	O
+13	O
+kb	O
+transcript	O
+,	O
+which	O
+was	O
+approximately	O
+twice	O
+as	O
+large	O
+as	O
+the	O
+mammalian	B-GENE
+lactase	I-GENE
+mRNA	I-GENE
+.	O
+
+In	O
+cell	O
+lines	O
+transformed	O
+by	O
+BCR	B-GENE
+/	O
+ABL	B-GENE
+,	O
+CRKL	B-GENE
+was	O
+tyrosine	O
+phosphorylated	O
+,	O
+while	O
+CRK	B-GENE
+was	O
+not	O
+.	O
+
+In	O
+untransformed	O
+cells	O
+,	O
+three	O
+major	O
+proteins	O
+coprecipitated	O
+with	O
+CRKL	B-GENE
+,	O
+identified	O
+as	O
+C3G	B-GENE
+,	O
+SOS	B-GENE
+and	O
+c	B-GENE
+-	I-GENE
+ABL	I-GENE
+.	O
+
+RESULTS	O
+:	O
+Nodular	O
+opacities	O
+,	O
+mainly	O
+centrilobular	O
+in	O
+distribution	O
+,	O
+were	O
+the	O
+most	O
+common	O
+finding	O
+,	O
+seen	O
+in	O
+21	O
+(	O
+72	O
+%	O
+)	O
+and	O
+15	O
+(	O
+65	O
+%	O
+)	O
+of	O
+patients	O
+with	O
+MTB	O
+and	O
+NTMB	O
+,	O
+respectively	O
+.	O
+
+Circulating	O
+oxytocin	B-GENE
+in	O
+male	O
+guinea	O
+pigs	O
+affected	O
+by	O
+the	O
+female	O
+cohabitation	O
+and	O
+reproductive	O
+condition	O
+.	O
+
+Antisense	O
+transcription	O
+of	O
+a	O
+murine	B-GENE
+FGFR	I-GENE
+-	I-GENE
+3	I-GENE
+psuedogene	I-GENE
+during	O
+fetal	O
+developement	O
+.	O
+
+A	O
+previous	O
+report	O
+described	O
+that	O
+a	O
+548	O
+-	O
+bp	O
+BglII	B-GENE
+-	O
+SmaI	B-GENE
+fragment	O
+has	O
+an	O
+SSO	O
+activity	O
+(	O
+ori2	O
+;	O
+Kataoka	O
+et	O
+al	O
+.	O
+,	O
+Mol	O
+.	O
+
+The	O
+human	B-GENE
+CD38	I-GENE
+gene	I-GENE
+consists	O
+of	O
+8	O
+exons	O
+that	O
+extend	O
+more	O
+than	O
+77	O
+kb	O
+on	O
+the	O
+human	O
+genome	O
+.	O
+
+Type	O
+IV	O
+splice	O
+pattern	O
+,	O
+containing	O
+exon	O
+U3	O
+and	O
+S	O
+was	O
+found	O
+both	O
+in	O
+kidney	O
+and	O
+ovary	O
+.	O
+
+GH	B-GENE
+deficiency	O
+may	O
+be	O
+absolute	O
+,	O
+but	O
+often	O
+is	O
+not	O
+and	O
+the	O
+diagnosis	O
+may	O
+be	O
+complicated	O
+by	O
+a	O
+constellation	O
+of	O
+physical	O
+and	O
+hormonal	O
+findings	O
+that	O
+are	O
+along	O
+a	O
+spectrum	O
+from	O
+low	O
+normal	O
+GH	B-GENE
+sufficiency	O
+to	O
+absent	O
+GH	B-GENE
+secretion	O
+.	O
+
+Positive	O
+CRP	B-GENE
+test	O
+were	O
+seen	O
+.	O
+
+During	O
+the	O
+febrile	O
+period	O
+,	O
+pleocytosis	O
+was	O
+associated	O
+with	O
+high	O
+levels	O
+of	O
+IgG	B-GENE
+,	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+,	O
+and	O
+PGE2	O
+in	O
+the	O
+cerebrospinal	O
+fluid	O
+.	O
+
+Recognition	O
+mechanisms	O
+of	O
+the	O
+minus	O
+-	O
+strand	O
+origin	O
+of	O
+phage	O
+f1	O
+by	O
+Escherichia	B-GENE
+coli	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+.	O
+
+The	O
+minimum	O
+and	O
+essential	O
+subunits	O
+for	O
+RNA	O
+synthesis	O
+have	O
+not	O
+yet	O
+been	O
+identified	O
+.	O
+
+Syndecan	B-GENE
+-	I-GENE
+4	I-GENE
+is	O
+a	O
+focal	O
+adhesion	O
+component	O
+,	O
+and	O
+this	O
+interaction	O
+may	O
+both	O
+localize	O
+PKC	B-GENE
+and	O
+amplify	O
+its	O
+activity	O
+at	O
+sites	O
+of	O
+forming	O
+adhesions	O
+.	O
+
+The	O
+3ASubE	O
+cells	O
+expressing	O
+CXCR2	B-GENE
+with	O
+mutation	O
+of	O
+Ser	O
+-	O
+346	O
+,	O
+-	O
+347	O
+,	O
+and	O
+-	O
+348	O
+to	O
+alanine	O
+,	O
+or	O
+with	O
+mutation	O
+of	O
+only	O
+one	O
+serine	O
+in	O
+this	O
+domain	O
+,	O
+continue	O
+to	O
+be	O
+phosphorylated	O
+in	O
+response	O
+to	O
+ligand	O
+and	O
+are	O
+60	O
+-	O
+70	O
+%	O
+desensitized	O
+following	O
+the	O
+initial	O
+ligand	O
+challenge	O
+.	O
+
+Members	O
+of	O
+the	O
+MAPK	B-GENE
+family	I-GENE
+include	O
+the	O
+extracellular	B-GENE
+response	I-GENE
+kinases	I-GENE
+(	O
+ERKs	B-GENE
+or	O
+p42	B-GENE
+/	I-GENE
+44	I-GENE
+(	O
+MAPK	B-GENE
+)	O
+)	O
+,	O
+the	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+amino	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinases	I-GENE
+(	O
+JNKs	B-GENE
+)	O
+,	O
+and	O
+the	O
+p38	B-GENE
+/	O
+Hog	B-GENE
+1	I-GENE
+protein	O
+kinases	O
+.	O
+
+MOP5	B-GENE
+contained	O
+the	O
+characteristic	O
+PAS	B-GENE
+domain	O
+and	O
+a	O
+variable	O
+C	O
+terminus	O
+;	O
+it	O
+is	O
+possible	O
+that	O
+the	O
+cDNA	O
+contains	O
+a	O
+bHLH	O
+domain	O
+,	O
+but	O
+the	O
+entire	O
+open	O
+reading	O
+frame	O
+has	O
+yet	O
+to	O
+be	O
+completed	O
+.	O
+
+Some	O
+8	O
+.	O
+8	O
+kb	O
+of	O
+the	O
+Lactobacillus	O
+sake	O
+plasmid	O
+pCIM1	O
+was	O
+sequenced	O
+,	O
+revealing	O
+eight	O
+tightly	O
+clustered	O
+open	O
+reading	O
+frames	O
+(	O
+ORFs	O
+)	O
+downstream	O
+from	O
+lasA	B-GENE
+,	O
+which	O
+encodes	O
+pre	B-GENE
+-	I-GENE
+lactocin	I-GENE
+S	I-GENE
+.	O
+
+Purified	B-GENE
+Pra	I-GENE
+was	O
+also	O
+shown	O
+to	O
+physically	O
+interact	O
+with	O
+pyruvate	B-GENE
+kinase	I-GENE
+(	O
+Pk	B-GENE
+)	O
+;	O
+Pk	B-GENE
+and	O
+Pra	B-GENE
+can	O
+form	O
+a	O
+complex	O
+,	O
+but	O
+when	O
+the	O
+12	B-GENE
+-	I-GENE
+kDa	I-GENE
+Ndk	I-GENE
+,	O
+Pk	B-GENE
+,	O
+and	O
+Pra	B-GENE
+are	O
+all	O
+present	O
+,	O
+Pk	B-GENE
+has	O
+a	O
+higher	O
+affinity	O
+than	O
+Pra	B-GENE
+for	O
+forming	O
+a	O
+complex	O
+with	O
+the	O
+12	B-GENE
+-	I-GENE
+kDa	I-GENE
+Ndk	I-GENE
+.	O
+
+Molecular	O
+characterization	O
+of	O
+a	O
+large	O
+Borrelia	O
+burgdorferi	O
+motility	O
+operon	O
+which	O
+is	O
+initiated	O
+by	O
+a	O
+consensus	O
+sigma70	B-GENE
+promoter	I-GENE
+.	O
+
+M	B-GENE
+.	I-GENE
+leprae	I-GENE
+OxyR	I-GENE
+was	O
+overproduced	O
+and	O
+purified	O
+,	O
+and	O
+its	O
+binding	O
+to	O
+the	O
+oxyR	B-GENE
+-	O
+ahpC	B-GENE
+intergenic	O
+region	O
+of	O
+M	O
+.	O
+leprae	O
+was	O
+demonstrated	O
+.	O
+
+The	O
+binding	O
+site	O
+for	O
+OxyR	B-GENE
+overlapped	O
+P1oxyR	B-GENE
+,	O
+reminiscent	O
+of	O
+the	O
+autoregulatory	O
+loops	O
+controlling	O
+expression	O
+of	O
+oxyR	B-GENE
+in	O
+enteric	O
+bacteria	O
+and	O
+characteristic	O
+of	O
+the	O
+LysR	B-GENE
+superfamily	I-GENE
+in	O
+general	O
+.	O
+
+Thirty	O
+-	O
+five	O
+patients	O
+were	O
+included	O
+.	O
+
+Grade	O
+3	O
+-	O
+4	O
+mucositis	O
+was	O
+present	O
+in	O
+13	O
+%	O
+of	O
+the	O
+cycles	O
+.	O
+
+Therefore	O
+more	O
+active	O
+and	O
+tolerable	O
+salvage	O
+regimens	O
+are	O
+needed	O
+.	O
+
+None	O
+of	O
+these	O
+organic	O
+manifestations	O
+was	O
+discovered	O
+by	O
+scintigraphic	O
+means	O
+.	O
+
+While	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+does	O
+not	O
+alter	O
+the	O
+mitogen	O
+-	O
+induced	O
+expression	O
+and	O
+abundance	O
+of	O
+G1	O
+phase	O
+cyclin	B-GENE
+D1	I-GENE
+and	O
+cdks	B-GENE
+4	I-GENE
+and	I-GENE
+2	I-GENE
+in	O
+MCs	O
+,	O
+it	O
+inhibits	O
+cyclin	B-GENE
+E	I-GENE
+-	O
+cdk	B-GENE
+2	I-GENE
+activity	O
+,	O
+thus	O
+preventing	O
+mitogen	O
+-	O
+elicited	O
+phosphorylation	O
+and	O
+inactivation	O
+of	O
+pRb	B-GENE
+in	O
+G1	O
+phase	O
+and	O
+transition	O
+to	O
+S	O
+phase	O
+.	O
+
+However	O
+,	O
+the	O
+range	O
+of	O
+values	O
+observed	O
+is	O
+suggestive	O
+of	O
+the	O
+need	O
+to	O
+investigate	O
+districts	O
+with	O
+contrasting	O
+values	O
+of	O
+SYPLR	O
+with	O
+respect	O
+to	O
+the	O
+inter	O
+-	O
+relationships	O
+between	O
+sociodemographic	O
+characteristics	O
+,	O
+duration	O
+of	O
+symptoms	O
+,	O
+clinical	O
+presentation	O
+and	O
+treatment	O
+efficacy	O
+.	O
+
+The	O
+prominent	O
+lesions	O
+were	O
+confined	O
+to	O
+the	O
+cerebral	O
+surface	O
+layer	O
+and	O
+leptomeningeal	O
+tissue	O
+including	O
+the	O
+arachnoid	O
+vessels	O
+,	O
+which	O
+were	O
+all	O
+bathed	O
+in	O
+the	O
+cerebrospinal	O
+fluid	O
+,	O
+suggesting	O
+that	O
+some	O
+necrotizing	O
+toxins	O
+had	O
+been	O
+secreted	O
+into	O
+the	O
+fluid	O
+by	O
+the	O
+B	O
+.	O
+cereus	O
+.	O
+
+This	O
+fragment	O
+contained	O
+the	O
+C	O
+-	O
+terminal	O
+47	O
+nucleotides	O
+of	O
+leuB	B-GENE
+,	O
+encoding	O
+3	B-GENE
+-	I-GENE
+isopropylmalate	I-GENE
+dehydrogenase	I-GENE
+;	O
+asd	B-GENE
+,	O
+encoding	O
+aspartate	B-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+semialdehyde	I-GENE
+dehydrogenase	I-GENE
+(	O
+Asd	B-GENE
+)	O
+;	O
+and	O
+orfA	O
+,	O
+whose	O
+product	O
+showed	O
+similarity	O
+to	O
+the	O
+Asd	B-GENE
+proteins	I-GENE
+from	I-GENE
+Vibrio	I-GENE
+spp	I-GENE
+.	O
+
+Hovenitin	O
+I	O
+and	O
+(	O
++	O
+)	O
+-	O
+ampelopsin	O
+,	O
+both	O
+of	O
+which	O
+were	O
+principal	O
+ingredients	O
+of	O
+the	O
+active	O
+fractions	O
+from	O
+this	O
+natural	O
+medicine	O
+,	O
+were	O
+found	O
+to	O
+show	O
+an	O
+inhibitory	O
+activity	O
+on	O
+the	O
+ethanol	O
+-	O
+induced	O
+muscle	O
+relaxation	O
+in	O
+rats	O
+.	O
+
+Purified	B-GENE
+P7	I-GENE
+could	O
+be	O
+assembled	O
+onto	O
+particles	O
+lacking	O
+P7	B-GENE
+and	O
+particles	O
+lacking	O
+both	O
+P2	B-GENE
+(	O
+RNA	B-GENE
+polymerase	I-GENE
+)	O
+and	O
+P7	B-GENE
+.	O
+
+However	O
+,	O
+the	O
+same	O
+U1A	B-GENE
+peptide	I-GENE
+,	O
+when	O
+conjugated	O
+to	O
+BSA	B-GENE
+,	O
+inhibits	O
+vertebrate	B-GENE
+PAP	I-GENE
+.	O
+
+Plasma	O
+levels	O
+of	O
+protein	B-GENE
+C	I-GENE
+,	O
+protein	B-GENE
+S	I-GENE
+,	O
+and	O
+antithrombin	B-GENE
+III	I-GENE
+in	O
+patients	O
+with	O
+subarachnoid	O
+haemorrhage	O
+.	O
+
+Idiopathic	O
+bilateral	O
+recurrent	O
+branch	O
+retinal	O
+arterial	O
+occlusion	O
+(	O
+IBRBRAO	O
+)	O
+is	O
+a	O
+rare	O
+syndrome	O
+characterized	O
+by	O
+migraine	O
+headaches	O
+,	O
+tinnitus	O
+,	O
+vertigo	O
+,	O
+hearing	O
+loss	O
+,	O
+and	O
+recurrent	O
+branch	O
+retinal	O
+artery	O
+occlusion	O
+of	O
+unknown	O
+etiology	O
+.	O
+
+Epithelial	O
+and	O
+corneal	O
+thickness	O
+measurements	O
+by	O
+in	O
+vivo	O
+confocal	O
+microscopy	O
+through	O
+focusing	O
+(	O
+CMTF	O
+)	O
+.	O
+
+Sequences	O
+downstream	O
+of	O
+the	O
+two	O
+human	B-GENE
+CA	I-GENE
+genes	I-GENE
+,	O
+possibly	O
+containing	O
+homologous	O
+enhancer	O
+elements	O
+,	O
+have	O
+not	O
+yet	O
+been	O
+reported	O
+.	O
+
+Recombinant	O
+plasmids	O
+containing	O
+the	O
+entire	O
+322	O
+nt	O
+5	O
+'	O
+UTR	O
+of	O
+exon	O
+1	O
+and	O
+a	O
+1630	O
+nt	O
+segment	O
+of	O
+5	O
+'	O
+flanking	O
+sequence	O
+stimulated	O
+luciferase	B-GENE
+activity	O
+nearly	O
+70	O
+times	O
+higher	O
+than	O
+a	O
+promoterless	O
+control	O
+plasmid	O
+.	O
+
+Analysis	O
+for	O
+DNA	O
+-	O
+protein	O
+interactions	O
+by	O
+in	O
+vitro	O
+DNase	B-GENE
+-	I-GENE
+I	I-GENE
+footprinting	O
+identified	O
+a	O
+broad	O
+region	O
+of	O
+protection	O
+extending	O
+from	O
+nt	O
+-	O
+12	O
+to	O
++	O
+38	O
+.	O
+
+It	O
+is	O
+also	O
+homologous	O
+to	O
+other	O
+sugar	O
+carriers	O
+from	O
+human	O
+,	O
+mouse	O
+and	O
+Escherichia	O
+coli	O
+.	O
+
+Until	O
+now	O
+,	O
+each	O
+of	O
+these	O
+loci	O
+was	O
+considered	O
+to	O
+contain	O
+three	O
+genes	O
+(	O
+for	O
+regulator	B-GENE
+,	O
+permease	B-GENE
+and	O
+alpha	B-GENE
+-	I-GENE
+glucosidase	I-GENE
+)	O
+,	O
+but	O
+a	O
+fourth	O
+gene	O
+,	O
+presumably	O
+an	O
+extra	O
+alpha	B-GENE
+-	I-GENE
+glucosidase	I-GENE
+gene	I-GENE
+,	O
+was	O
+found	O
+at	O
+MAL1	B-GENE
+adjacent	O
+to	O
+the	O
+usual	O
+cluster	O
+of	O
+three	O
+genes	O
+.	O
+
+Autorosette	O
+-	O
+forming	O
+cells	O
+are	O
+characterized	O
+by	O
+a	O
+high	O
+activity	O
+of	O
+alkaline	B-GENE
+and	I-GENE
+acid	I-GENE
+phosphatases	I-GENE
+and	O
+low	O
+NBT	O
+-	O
+test	O
+values	O
+.	O
+
+Analysis	O
+of	O
+homologous	O
+DNA	O
+sequences	O
+within	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+mouse	B-GENE
+and	I-GENE
+human	I-GENE
+mts1	I-GENE
+genes	I-GENE
+:	O
+kB	B-GENE
+-	I-GENE
+like	I-GENE
+site	I-GENE
+and	O
+microsatellite	O
+DNA	O
+
+The	O
+integration	O
+at	O
+the	O
+VIP	B-GENE
+CyRE	B-GENE
+of	O
+the	O
+Jak	B-GENE
+-	O
+Stat	B-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+signaling	O
+pathways	O
+with	O
+other	O
+pre	O
+-	O
+existing	O
+proteins	O
+provides	O
+a	O
+cellular	O
+mechanism	O
+for	O
+cell	O
+-	O
+and	O
+cytokine	O
+-	O
+specific	O
+signaling	O
+.	O
+
+These	O
+studies	O
+point	O
+to	O
+the	O
+involvement	O
+of	O
+the	O
+MAP	B-GENE
+kinase	I-GENE
+pathway	O
+in	O
+the	O
+activation	O
+of	O
+monocytic	O
+cells	O
+during	O
+transmigration	O
+to	O
+inflammatory	O
+sites	O
+.	O
+
+Our	O
+results	O
+show	O
+that	O
+the	O
+temperature	B-GENE
+-	I-GENE
+sensitive	I-GENE
+rad54	I-GENE
+-	I-GENE
+3	I-GENE
+allele	I-GENE
+blocks	O
+mitotic	O
+recombination	O
+between	O
+tandemly	O
+repeated	O
+DYZ3	B-GENE
+satellite	I-GENE
+sequences	I-GENE
+and	O
+significantly	O
+stabilizes	O
+a	O
+human	B-GENE
+DYZ5	I-GENE
+satellite	O
+-	O
+containing	O
+YAC	O
+clone	O
+.	O
+
+A	O
+P22	O
+R17	O
+derivative	O
+with	O
+an	O
+OcRNA	O
+site	O
+(	O
+P22	O
+R17	O
+[	O
+A	O
+(	O
+-	O
+10	O
+)	O
+U	O
+]	O
+)	O
+develops	O
+lytically	O
+following	O
+infection	O
+of	O
+these	O
+strains	O
+.	O
+
+Circularized	O
+Ac	B-GENE
+/	O
+Ds	B-GENE
+transposons	O
+:	O
+formation	O
+,	O
+structure	O
+and	O
+fate	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+have	O
+examined	O
+the	O
+regulation	O
+of	O
+B	B-GENE
+-	I-GENE
+Myb	I-GENE
+activity	O
+by	O
+cyclin	B-GENE
+-	O
+Cdks	B-GENE
+.	O
+
+Candidate	O
+tumor	O
+suppressor	O
+genes	O
+,	O
+Mts1	B-GENE
+(	O
+p16INK4a	B-GENE
+)	O
+and	O
+Mts2	B-GENE
+(	O
+p15INK4b	B-GENE
+)	O
+,	O
+have	O
+been	O
+mapped	O
+to	O
+this	O
+region	O
+,	O
+but	O
+by	O
+Southern	O
+blot	O
+analysis	O
+,	O
+no	O
+homozygous	O
+deletions	O
+were	O
+detected	O
+in	O
+either	O
+gene	O
+.	O
+
+Excision	O
+repair	O
+at	O
+the	O
+level	O
+of	O
+the	O
+nucleotide	O
+in	O
+the	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+MFA2	I-GENE
+gene	I-GENE
+:	O
+mapping	O
+of	O
+where	O
+enhanced	O
+repair	O
+in	O
+the	O
+transcribed	O
+strand	O
+begins	O
+or	O
+ends	O
+and	O
+identification	O
+of	O
+only	O
+a	O
+partial	O
+rad16	B-GENE
+requisite	O
+for	O
+repairing	O
+upstream	O
+control	O
+sequences	O
+.	O
+
+This	O
+locus	O
+maps	O
+approximately	O
+160	O
+kbp	O
+from	O
+the	O
+genes	O
+encoding	O
+cytadherence	O
+-	O
+associated	O
+proteins	O
+HMW1	B-GENE
+and	O
+HMW3	B-GENE
+,	O
+and	O
+yet	O
+insertions	O
+therein	O
+result	O
+in	O
+loss	O
+of	O
+these	O
+proteins	O
+and	O
+a	O
+hemadsorption	O
+-	O
+negative	O
+(	O
+HA	O
+-	O
+)	O
+phenotype	O
+,	O
+prompting	O
+the	O
+designation	O
+cytadherence	B-GENE
+-	I-GENE
+regulatory	I-GENE
+locus	I-GENE
+(	O
+crl	B-GENE
+)	O
+.	O
+
+Coliphage	B-GENE
+186	I-GENE
+B	I-GENE
+is	O
+a	O
+72	O
+-	O
+amino	O
+acid	O
+protein	O
+belonging	O
+to	O
+the	O
+Ogr	B-GENE
+family	O
+of	O
+analogous	O
+transcription	O
+factors	O
+present	O
+in	O
+P2	O
+-	O
+like	O
+phage	O
+,	O
+which	O
+contain	O
+a	O
+Cys	O
+-	O
+X2	O
+-	O
+Cys	O
+-	O
+X22	O
+-	O
+Cys	O
+-	O
+X4	O
+-	O
+Cys	O
+presumptive	O
+zinc	O
+-	O
+finger	O
+motif	O
+.	O
+
+The	O
+UV	O
+absorption	O
+spectrum	O
+revealed	O
+a	O
+shoulder	O
+at	O
+250	O
+nm	O
+,	O
+characteristic	O
+of	O
+CysS	O
+-	O
+Cd	O
+(	O
+II	O
+)	O
+ligand	O
+-	O
+to	O
+-	O
+metal	O
+charge	O
+-	O
+transfer	O
+transitions	O
+,	O
+and	O
+the	O
+difference	O
+absorption	O
+coefficient	O
+after	O
+acidification	O
+(	O
+delta	O
+epsilon	O
+248	O
+,	O
+24	O
+mM	O
+-	O
+1	O
+cm	O
+-	O
+1	O
+)	O
+indicated	O
+the	O
+presence	O
+of	O
+a	O
+Cd	O
+(	O
+Cys	O
+-	O
+S	O
+)	O
+4	O
+center	O
+.	O
+
+Diacylglycerol	B-GENE
+kinase	I-GENE
+(	O
+DGK	B-GENE
+)	O
+attenuates	O
+levels	O
+of	O
+second	O
+messenger	O
+diacylglycerol	O
+in	O
+cells	O
+and	O
+produces	O
+another	O
+(	O
+putative	O
+)	O
+messenger	O
+,	O
+phosphatidic	O
+acid	O
+.	O
+
+Recently	O
+,	O
+we	O
+have	O
+reported	O
+the	O
+cloning	O
+of	O
+the	O
+germ	O
+cell	O
+-	O
+specific	O
+,	O
+nuclear	O
+orphan	O
+receptor	O
+germ	B-GENE
+cell	I-GENE
+nuclear	I-GENE
+factor	I-GENE
+(	O
+GCNF	B-GENE
+)	O
+/	O
+RTR	B-GENE
+.	O
+
+Based	O
+on	O
+the	O
+sequence	O
+of	O
+the	O
+conRTRE	B-GENE
+,	O
+we	O
+located	O
+a	O
+putative	O
+RTRE	B-GENE
+,	O
+referred	O
+to	O
+as	O
+P2	B-GENE
+-	I-GENE
+RE	I-GENE
+,	O
+in	O
+the	O
+5	O
+'	O
+promoter	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+mouse	B-GENE
+protamine	I-GENE
+2	I-GENE
+gene	I-GENE
+,	O
+which	O
+is	O
+induced	O
+during	O
+the	O
+same	O
+stage	O
+of	O
+spermatogenesis	O
+as	O
+RTR	B-GENE
+.	O
+
+Active	O
+complexes	O
+eluted	O
+at	O
+a	O
+higher	O
+molecular	O
+weight	O
+than	O
+inactive	O
+complexes	O
+,	O
+were	O
+relatively	O
+deficient	O
+in	O
+both	O
+p21	B-GENE
+and	O
+p27	B-GENE
+,	O
+and	O
+contained	O
+Cdk2	B-GENE
+with	O
+increased	O
+threonine	O
+160	O
+phosphorylation	O
+,	O
+consistent	O
+with	O
+a	O
+mechanism	O
+of	O
+activation	O
+of	O
+cyclin	B-GENE
+E	I-GENE
+-	O
+Cdk2	B-GENE
+involving	O
+both	O
+reduced	O
+CDK	B-GENE
+inhibitor	O
+association	O
+and	O
+CDK	B-GENE
+-	I-GENE
+activating	I-GENE
+kinase	I-GENE
+-	O
+mediated	O
+phosphorylation	O
+of	O
+Cdk2	B-GENE
+.	O
+
+Thirty	O
+Class	O
+I	O
+and	O
+Class	O
+II	O
+recessions	O
+in	O
+30	O
+patients	O
+were	O
+treated	O
+with	O
+a	O
+modified	O
+subepithelial	O
+connective	O
+tissue	O
+graft	O
+procedure	O
+.	O
+
+The	O
+derivatives	O
+of	O
+the	O
+latter	O
+two	O
+cell	O
+lines	O
+showed	O
+increased	O
+expression	O
+of	O
+the	O
+p27Kip1	B-GENE
+protein	I-GENE
+and	O
+inhibition	O
+of	O
+cell	O
+growth	O
+.	O
+
+The	O
+perioperative	O
+mortality	O
+of	O
+all	O
+patients	O
+was	O
+1	O
+.	O
+9	O
+%	O
+,	O
+the	O
+mortality	O
+of	O
+patients	O
+older	O
+than	O
+70	O
+years	O
+was	O
+4	O
+.	O
+3	O
+%	O
+.	O
+
+Chronic	O
+renal	O
+failure	O
+patients	O
+essentially	O
+die	O
+from	O
+cardiovascular	O
+causes	O
+,	O
+and	O
+the	O
+frequency	O
+of	O
+malignant	O
+disease	O
+responsible	O
+for	O
+death	O
+is	O
+estimated	O
+to	O
+be	O
+10	O
+%	O
+.	O
+
+The	O
+new	O
+FIGO	O
+definition	O
+of	O
+cervical	O
+cancer	O
+stage	O
+IA	O
+:	O
+a	O
+critique	O
+.	O
+
+The	O
+effect	O
+of	O
+Vpu	B-GENE
+on	O
+class	O
+I	O
+biogenesis	O
+was	O
+analyzed	O
+in	O
+more	O
+detail	O
+using	O
+a	O
+Vpu	B-GENE
+-	O
+expressing	O
+recombinant	O
+vaccinia	O
+virus	O
+(	O
+VV	O
+)	O
+.	O
+
+Inductively	O
+coupled	O
+plasma	O
+atomic	O
+emission	O
+spectroscopy	O
+was	O
+employed	O
+to	O
+obtain	O
+the	O
+tissue	O
+silicon	O
+measurements	O
+.	O
+
+An	O
+egg	O
+protein	O
+,	O
+lysozyme	B-GENE
+,	O
+is	O
+a	O
+still	O
+unlabeled	O
+additive	O
+currently	O
+used	O
+in	O
+cheese	O
+preparation	O
+.	O
+
+Similarly	O
+,	O
+the	O
+DNA	O
+-	O
+binding	O
+activity	O
+of	O
+activator	B-GENE
+protein	I-GENE
+1	I-GENE
+(	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+is	O
+modified	O
+by	O
+a	O
+DNA	B-GENE
+repair	I-GENE
+enzyme	I-GENE
+,	O
+redox	B-GENE
+factor	I-GENE
+1	I-GENE
+(	O
+Ref	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+which	O
+is	O
+identical	O
+to	O
+a	O
+DNA	B-GENE
+repair	I-GENE
+enzyme	I-GENE
+,	O
+AP	B-GENE
+endonuclease	I-GENE
+.	O
+
+Having	O
+an	O
+LRR	B-GENE
+domain	I-GENE
+and	O
+an	O
+SH3	B-GENE
+-	I-GENE
+binding	I-GENE
+domain	I-GENE
+,	O
+Acan125	B-GENE
+and	O
+the	O
+C	O
+.	O
+elegans	O
+homologue	O
+define	O
+a	O
+novel	O
+family	O
+of	O
+bifunctional	O
+binding	O
+proteins	O
+.	O
+
+However	O
+,	O
+its	O
+participation	O
+in	O
+gagging	O
+induced	O
+by	O
+oropharyngeal	O
+irritation	O
+is	O
+unclear	O
+.	O
+
+The	O
+capacity	O
+to	O
+repair	O
+8	O
+-	O
+OxoG	O
+has	O
+been	O
+measured	O
+in	O
+cell	O
+-	O
+free	O
+extracts	O
+of	O
+wild	O
+-	O
+type	O
+and	O
+ogg1	B-GENE
+strains	O
+using	O
+a	O
+34mer	O
+DNA	O
+fragment	O
+containing	O
+a	O
+single	O
+8	O
+-	O
+OxoG	O
+residue	O
+paired	O
+with	O
+a	O
+cytosine	O
+(	O
+8	O
+-	O
+OxoG	O
+/	O
+C	O
+)	O
+as	O
+a	O
+substrate	O
+.	O
+
+Results	O
+from	O
+our	O
+and	O
+other	O
+laboratories	O
+have	O
+suggested	O
+that	O
+UCN	O
+-	O
+01	O
+induces	O
+preferential	O
+G1	O
+-	O
+phase	O
+accumulation	O
+in	O
+several	O
+human	O
+tumor	O
+cell	O
+lines	O
+tested	O
+.	O
+
+Northern	O
+and	O
+RT	O
+-	O
+PCR	O
+analysis	O
+of	O
+Ube3a	B-GENE
+expression	O
+in	O
+mouse	O
+tissues	O
+from	O
+animals	O
+with	O
+segmental	O
+,	O
+paternal	O
+uniparental	O
+disomy	O
+failed	O
+to	O
+detect	O
+substantially	O
+reduced	O
+or	O
+absent	O
+expression	O
+compared	O
+to	O
+control	O
+animals	O
+,	O
+failing	O
+to	O
+provide	O
+any	O
+evidence	O
+for	O
+maternal	O
+-	O
+specific	O
+expression	O
+from	O
+this	O
+locus	O
+.	O
+
+Two	O
+predominant	O
+effects	O
+were	O
+noted	O
+:	O
+(	O
+i	O
+)	O
+the	O
+Xaa	O
+residue	O
+in	O
+the	O
+dual	O
+phosphorylation	O
+motif	O
+Thr	O
+-	O
+Xaa	O
+-	O
+Tyr	O
+as	O
+well	O
+as	O
+the	O
+length	O
+of	O
+L12	O
+influence	O
+p38	B-GENE
+substrate	O
+specificity	O
+,	O
+and	O
+(	O
+ii	O
+)	O
+the	O
+length	O
+of	O
+L12	O
+plays	O
+a	O
+major	O
+role	O
+in	O
+controlling	O
+autophosphorylation	O
+.	O
+
+A	O
+novel	O
+,	O
+testis	B-GENE
+-	I-GENE
+specific	I-GENE
+mRNA	I-GENE
+transcript	I-GENE
+encoding	O
+an	O
+NH2	B-GENE
+-	I-GENE
+terminal	I-GENE
+truncated	I-GENE
+nitric	I-GENE
+-	I-GENE
+oxide	I-GENE
+synthase	I-GENE
+.	O
+mRNA	O
+diversity	O
+represents	O
+a	O
+major	O
+theme	O
+of	O
+neuronal	B-GENE
+nitric	I-GENE
+-	I-GENE
+oxide	I-GENE
+synthase	I-GENE
+(	O
+nNOS	B-GENE
+)	O
+gene	O
+expression	O
+in	O
+somatic	O
+cells	O
+/	O
+tissues	O
+.	O
+
+Unlike	O
+the	O
+MAR	O
+-	O
+binding	O
+domain	O
+,	O
+the	O
+homeodomain	B-GENE
+when	O
+isolated	O
+binds	O
+poorly	O
+and	O
+with	O
+low	O
+specificity	O
+to	O
+DNA	O
+.	O
+
+Cyclin	B-GENE
+D1	I-GENE
+could	O
+not	O
+be	O
+displaced	O
+from	O
+cdk4	B-GENE
+in	O
+the	O
+resistant	O
+184A1L5R	O
+cell	O
+lysates	O
+.	O
+
+The	O
+importance	O
+of	O
+posttranslational	O
+regulation	O
+of	O
+p15INK4B	B-GENE
+by	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+is	O
+underlined	O
+by	O
+the	O
+observation	O
+that	O
+in	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+-	O
+resistant	O
+184A1L5R	O
+,	O
+although	O
+the	O
+p15	B-GENE
+transcript	I-GENE
+increased	O
+,	O
+p15INK4B	B-GENE
+protein	I-GENE
+was	O
+not	O
+stabilized	O
+and	O
+did	O
+not	O
+accumulate	O
+,	O
+and	O
+cyclin	B-GENE
+D1	I-GENE
+-	O
+cdk	B-GENE
+association	O
+and	O
+kinase	O
+activation	O
+were	O
+not	O
+inhibited	O
+.	O
+
+To	O
+identify	O
+cis	O
+-	O
+acting	O
+elements	O
+that	O
+target	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+mRNA	I-GENE
+for	O
+downregulation	O
+during	O
+myogenesis	O
+,	O
+we	O
+stably	O
+transfected	O
+C2C12	O
+cells	O
+with	O
+mutant	B-GENE
+myc	I-GENE
+genes	I-GENE
+or	O
+chimeric	O
+genes	O
+in	O
+which	O
+various	O
+myc	B-GENE
+sequences	I-GENE
+were	O
+fused	O
+to	O
+the	O
+human	B-GENE
+beta	I-GENE
+-	I-GENE
+globin	I-GENE
+gene	I-GENE
+or	O
+to	O
+the	O
+bacterial	B-GENE
+chloramphenicol	I-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+gene	O
+.	O
+
+Furthermore	O
+,	O
+experiments	O
+with	O
+32D	O
+temperature	O
+-	O
+sensitive	O
+p53	B-GENE
+cells	O
+indicate	O
+that	O
+aberrant	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+at	O
+the	O
+permissive	O
+temperature	O
+does	O
+not	O
+exert	O
+a	O
+proliferative	O
+effect	O
+but	O
+causes	O
+p53	B-GENE
+-	O
+mediated	O
+apoptosis	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+proliferative	O
+effect	O
+depends	O
+on	O
+the	O
+integrity	O
+of	O
+the	O
+cell	O
+cycle	O
+checkpoints	O
+of	O
+the	O
+host	O
+cell	O
+,	O
+as	O
+observed	O
+for	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+and	O
+other	O
+oncogenes	O
+.	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+experiments	O
+indicate	O
+that	O
+ectopic	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+effects	O
+are	O
+mediated	O
+by	O
+both	O
+the	O
+DNA	O
+-	O
+binding	O
+and	O
+the	O
+heterodimerization	O
+domains	O
+,	O
+while	O
+the	O
+N	B-GENE
+-	I-GENE
+terminally	I-GENE
+truncated	I-GENE
+tal	I-GENE
+-	I-GENE
+1	I-GENE
+variant	I-GENE
+(	O
+M3	B-GENE
+)	O
+expressed	O
+in	O
+T	O
+-	O
+ALL	O
+malignant	O
+cells	O
+mimics	O
+the	O
+effects	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+protein	O
+.	O
+
+DNA	O
+-	O
+binding	O
+activity	O
+was	O
+not	O
+increased	O
+by	O
+the	O
+addition	O
+of	O
+forskolin	O
+to	O
+thecal	O
+or	O
+luteal	O
+cells	O
+.	O
+
+However	O
+,	O
+in	O
+some	O
+of	O
+them	O
+either	O
+pattern	O
+may	O
+predominate	O
+or	O
+be	O
+exclusively	O
+present	O
+.	O
+
+Upon	O
+induction	O
+of	O
+SOS	O
+,	O
+viability	O
+increased	O
+2	O
+-	O
+6	O
+-	O
+fold	O
+.	O
+
+In	O
+particular	O
+,	O
+Western	O
+,	O
+supershift	O
+,	O
+and	O
+promoter	O
+deletion	O
+analyses	O
+suggested	O
+a	O
+role	O
+for	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+-	I-GENE
+beta	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+-	I-GENE
+beta	I-GENE
+)	O
+binding	O
+site	O
+between	O
+-	O
+2010	O
+and	O
+-	O
+1954	O
+in	O
+regulating	O
+transcription	O
+of	O
+collagenase	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+monocytic	O
+cells	O
+.	O
+
+11	O
+-	O
+Aminoundecanoyl	O
+-	O
+SK	O
+-	O
+NH2	O
+and	O
+11	O
+-	O
+aminoundecanoyl	O
+-	O
+SH	O
+-	O
+NH2	O
+establish	O
+that	O
+a	O
+simple	O
+alkyl	O
+backbone	O
+can	O
+maintain	O
+an	O
+appropriate	O
+distance	O
+between	O
+three	O
+elements	O
+critical	O
+for	O
+recognition	O
+by	O
+the	O
+fungal	O
+enzyme	O
+'	O
+s	O
+peptide	O
+-	O
+binding	O
+site	O
+:	O
+a	O
+simple	O
+omega	O
+-	O
+terminal	O
+amino	O
+group	O
+,	O
+a	O
+beta	O
+-	O
+hydroxyl	O
+,	O
+and	O
+an	O
+epsilon	O
+-	O
+amino	O
+group	O
+or	O
+an	O
+imidazole	O
+.	O
+
+Cdc2	B-GENE
+co	O
+-	O
+precipitates	O
+with	O
+Pch1	B-GENE
+in	O
+S	O
+.	O
+pombe	O
+cell	O
+lysates	O
+,	O
+although	O
+Cdc2	B-GENE
+may	O
+not	O
+be	O
+the	O
+major	O
+catalytic	O
+partner	O
+of	O
+a	O
+Pch1	B-GENE
+kinase	I-GENE
+in	O
+vivo	O
+.	O
+
+Little	O
+is	O
+known	O
+about	O
+the	O
+mechanism	O
+,	O
+but	O
+the	O
+availability	O
+of	O
+rapid	O
+facile	O
+assays	O
+for	O
+monitoring	O
+immunoglobulin	B-GENE
+hypermutation	O
+would	O
+greatly	O
+aid	O
+the	O
+development	O
+of	O
+culture	O
+systems	O
+for	O
+hypermutating	O
+B	O
+cells	O
+as	O
+well	O
+as	O
+the	O
+screening	O
+for	O
+individuals	O
+deficient	O
+in	O
+the	O
+process	O
+.	O
+
+Expression	O
+of	O
+the	O
+human	B-GENE
+heat	I-GENE
+shock	I-GENE
+protein	I-GENE
+70	I-GENE
+gene	I-GENE
+(	O
+hsp70	B-GENE
+)	O
+is	O
+induced	O
+by	O
+various	O
+kinds	O
+of	O
+stress	O
+and	O
+by	O
+oncogenes	O
+.	O
+
+Of	O
+these	O
+proteins	O
+,	O
+five	O
+have	O
+previously	O
+been	O
+shown	O
+to	O
+be	O
+phosphorylated	O
+during	O
+mitosis	O
+(	O
+epithelial	B-GENE
+-	I-GENE
+microtubule	I-GENE
+associated	I-GENE
+protein	I-GENE
+-	I-GENE
+115	I-GENE
+,	O
+Oct91	B-GENE
+,	O
+Elongation	B-GENE
+factor	I-GENE
+1gamma	I-GENE
+,	O
+BRG1	B-GENE
+and	O
+Ribosomal	B-GENE
+protein	I-GENE
+L18A	I-GENE
+)	O
+,	O
+five	O
+are	O
+related	O
+to	O
+proteins	O
+postulated	O
+to	O
+have	O
+roles	O
+in	O
+mitosis	O
+(	O
+epithelial	B-GENE
+-	I-GENE
+microtubule	I-GENE
+associated	I-GENE
+protein	I-GENE
+-	I-GENE
+115	I-GENE
+,	O
+Schizosaccharomyces	B-GENE
+pombe	I-GENE
+Cdc5	I-GENE
+,	O
+innercentrosome	B-GENE
+protein	I-GENE
+,	O
+BRG1	B-GENE
+and	O
+the	O
+RNA	B-GENE
+helicase	I-GENE
+WM6	I-GENE
+)	O
+,	O
+and	O
+nine	O
+are	O
+related	O
+to	O
+transcription	O
+factors	O
+(	O
+BRG1	B-GENE
+,	O
+negative	B-GENE
+co	I-GENE
+-	I-GENE
+factor	I-GENE
+2alpha	I-GENE
+,	O
+Oct91	B-GENE
+,	O
+S	O
+.	O
+pombe	O
+Cdc5	B-GENE
+,	O
+HoxD1	B-GENE
+,	O
+Sox3	B-GENE
+,	O
+Vent2	B-GENE
+,	O
+and	O
+two	O
+isoforms	O
+of	O
+Xbr1b	B-GENE
+)	O
+.	O
+
+Thus	O
+,	O
+depending	O
+on	O
+their	O
+location	O
+,	O
+psoralen	O
+cross	O
+-	O
+links	O
+affected	O
+different	O
+steps	O
+in	O
+the	O
+initiation	O
+process	O
+.	O
+
+Activation	O
+of	O
+alpha	B-GENE
+4	I-GENE
+beta	I-GENE
+1	I-GENE
+with	O
+TS2	B-GENE
+/	I-GENE
+16	I-GENE
+inhibited	O
+the	O
+cytoplasmic	O
+protrusions	O
+and	O
+cell	O
+migration	O
+but	O
+did	O
+not	O
+affect	O
+the	O
+pattern	O
+of	O
+phosphorylation	O
+.	O
+
+Performance	O
+on	O
+two	O
+verbal	O
+measures	O
+-	O
+the	O
+National	O
+Adult	O
+Reading	O
+Test	O
+-	O
+Revised	O
+(	O
+NART	O
+-	O
+R	O
+)	O
+and	O
+the	O
+Vocabulary	O
+subtest	O
+from	O
+the	O
+Wechsler	O
+Adult	O
+Intelligence	O
+Scale	O
+-	O
+Revised	O
+(	O
+WAIS	O
+-	O
+R	O
+)	O
+-	O
+showed	O
+strong	O
+correlations	O
+with	O
+level	O
+of	O
+education	O
+.	O
+
+L	O
+-	O
+canavanine	O
+,	O
+a	O
+selective	O
+inhibitor	O
+of	O
+the	O
+inducible	O
+nitric	B-GENE
+oxide	I-GENE
+synthase	I-GENE
+,	O
+increases	O
+the	O
+mean	O
+systemic	O
+filling	O
+pressure	O
+,	O
+thereby	O
+improving	O
+venous	O
+return	O
+,	O
+under	O
+these	O
+conditions	O
+.	O
+
+RESULTS	O
+:	O
+Of	O
+the	O
+29	O
+patients	O
+who	O
+received	O
+concurrent	O
+chemotherapy	O
+and	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+,	O
+ten	O
+(	O
+34	O
+%	O
+;	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+,	O
+17	O
+.	O
+9	O
+to	O
+54	O
+.	O
+3	O
+%	O
+)	O
+were	O
+believed	O
+to	O
+have	O
+clinically	O
+significant	O
+bleomycin	O
+toxicity	O
+.	O
+
+The	O
+exonic	O
+sequence	O
+encodes	O
+a	O
+protein	O
+of	O
+495	O
+amino	O
+acids	O
+that	O
+is	O
+nearly	O
+identical	O
+to	O
+the	O
+previously	O
+reported	O
+protein	O
+sequence	O
+of	O
+human	B-GENE
+GPT	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Here	O
+we	O
+characterize	O
+an	O
+S	B-GENE
+.	I-GENE
+cerevisiae	I-GENE
+Swi3	I-GENE
+homolog	I-GENE
+(	O
+Swh3	B-GENE
+)	O
+and	O
+present	O
+evidence	O
+that	O
+it	O
+associates	O
+in	O
+a	O
+complex	O
+with	O
+a	O
+Snf2	B-GENE
+homolog	I-GENE
+,	O
+Sthl	B-GENE
+.	O
+
+Shc	B-GENE
+stimulates	O
+Ras	B-GENE
+/	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+MAPK	B-GENE
+)	O
+through	O
+forming	O
+a	O
+complex	O
+with	O
+Grb2	B-GENE
+at	O
+the	O
+phosphorylated	O
+tyrosine	O
+(	O
+Y	O
+)	O
+residue	O
+317	O
+.	O
+
+In	O
+contrast	O
+,	O
+Y239	B-GENE
+/	I-GENE
+240F	I-GENE
+Shc	I-GENE
+,	O
+but	O
+not	O
+Y317F	B-GENE
+Shc	I-GENE
+,	O
+reduced	O
+the	O
+EGF	B-GENE
+-	O
+induced	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+message	O
+.	O
+
+The	O
+Ras	B-GENE
+guanine	I-GENE
+nucleotide	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+functions	O
+as	O
+a	O
+molecular	O
+switch	O
+in	O
+signalling	O
+downstream	O
+of	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+.	O
+
+We	O
+show	O
+that	O
+Rlm1	B-GENE
+and	O
+Smp1	B-GENE
+have	O
+MEF2	B-GENE
+-	O
+related	O
+DNA	O
+-	O
+binding	O
+specificities	O
+:	O
+Rlm1	B-GENE
+binds	O
+with	O
+the	O
+same	O
+specificity	O
+as	O
+MEF2	B-GENE
+,	O
+CTA	B-GENE
+(	I-GENE
+T	I-GENE
+/	I-GENE
+A	I-GENE
+)	I-GENE
+4TAG	I-GENE
+,	O
+while	O
+SMP1	B-GENE
+binds	O
+a	O
+more	O
+extended	O
+consensus	O
+sequence	O
+,	O
+ACTACTA	O
+(	O
+T	O
+/	O
+A	O
+)	O
+4TAG	O
+.	O
+
+Domains	O
+I	O
+and	O
+II	O
+of	O
+B	B-GENE
+"	I-GENE
+are	O
+buried	O
+upon	O
+assembly	O
+of	O
+the	O
+TFIIIB	B-GENE
+-	I-GENE
+DNA	I-GENE
+complex	I-GENE
+,	O
+as	O
+determined	O
+by	O
+protein	O
+footprinting	O
+.	O
+
+Domain	O
+switch	O
+experiments	O
+reveal	O
+that	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+proteins	I-GENE
+containing	O
+either	O
+the	O
+leucine	O
+zipper	O
+or	O
+the	O
+activation	O
+domain	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+alpha	I-GENE
+are	O
+unable	O
+to	O
+stimulate	O
+the	O
+2D5	B-GENE
+promoter	I-GENE
+yet	O
+are	O
+fully	O
+capable	O
+of	O
+transactivating	O
+an	O
+artificial	O
+promoter	O
+bearing	O
+a	O
+high	O
+-	O
+affinity	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+site	I-GENE
+.	O
+
+PRH75	B-GENE
+,	O
+a	O
+new	O
+nucleus	O
+-	O
+localized	O
+member	O
+of	O
+the	O
+DEAD	B-GENE
+-	I-GENE
+box	I-GENE
+protein	I-GENE
+family	I-GENE
+from	O
+higher	O
+plants	O
+.	O
+
+These	O
+activities	O
+are	O
+all	O
+required	O
+for	O
+stimulation	O
+of	O
+cell	O
+growth	O
+by	O
+middle	B-GENE
+-	I-GENE
+T	I-GENE
+and	O
+activate	O
+members	O
+of	O
+the	O
+MAP	B-GENE
+kinase	I-GENE
+family	I-GENE
+.	O
+
+A	O
+role	O
+for	O
+the	O
+small	B-GENE
+GTPase	I-GENE
+Rac	I-GENE
+in	O
+polyomavirus	B-GENE
+middle	I-GENE
+-	I-GENE
+T	I-GENE
+antigen	I-GENE
+-	O
+mediated	O
+activation	O
+of	O
+the	O
+serum	O
+response	O
+element	O
+and	O
+in	O
+cell	O
+transformation	O
+.	O
+
+Time	O
+-	O
+activity	O
+curves	O
+from	O
+the	O
+gastric	O
+region	O
+of	O
+interest	O
+were	O
+used	O
+,	O
+after	O
+subjection	O
+to	O
+appropriate	O
+corrective	O
+procedures	O
+,	O
+to	O
+calculate	O
+the	O
+mean	O
+gastric	O
+transit	O
+time	O
+(	O
+MTT	O
+90	O
+)	O
+and	O
+the	O
+fraction	O
+of	O
+the	O
+test	O
+meal	O
+retained	O
+in	O
+the	O
+stomach	O
+after	O
+90	O
+min	O
+(	O
+F90	O
+)	O
+.	O
+
+This	O
+study	O
+provides	O
+a	O
+direct	O
+demonstration	O
+of	O
+a	O
+role	O
+for	O
+G	B-GENE
+betagamma	I-GENE
+in	O
+mediating	O
+the	O
+agonist	O
+-	O
+stimulated	O
+translocation	O
+of	O
+GRK2	B-GENE
+and	O
+GRK3	B-GENE
+in	O
+an	O
+intact	O
+cellular	O
+system	O
+and	O
+demonstrates	O
+isoform	O
+specificity	O
+in	O
+the	O
+interaction	O
+of	O
+these	O
+components	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+RA	O
+-	O
+mediated	O
+repression	O
+of	O
+the	O
+hMGP	B-GENE
+gene	I-GENE
+is	O
+due	O
+to	O
+binding	O
+of	O
+liganded	O
+RAR	B-GENE
+/	O
+RXR	B-GENE
+to	O
+a	O
+novel	O
+negative	O
+RA	O
+response	O
+element	O
+.	O
+
+Point	O
+mutations	O
+of	O
+the	O
+five	O
+tyrosine	O
+residues	O
+in	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+the	O
+receptor	O
+were	O
+subsequently	O
+used	O
+to	O
+confirm	O
+our	O
+conclusions	O
+.	O
+
+We	O
+describe	O
+a	O
+novel	O
+method	O
+using	O
+Saccharomyces	O
+cerevisiae	O
+for	O
+detecting	O
+protein	O
+-	O
+truncating	O
+mutations	O
+in	O
+any	O
+gene	O
+of	O
+interest	O
+.	O
+
+Hepatocellular	O
+injury	O
+during	O
+preservation	O
+of	O
+human	O
+livers	O
+with	O
+UW	O
+and	O
+HTK	O
+solution	O
+.	O
+
+The	O
+electromyographically	O
+recorded	O
+responses	O
+consisted	O
+of	O
+an	O
+early	O
+R1	O
+response	O
+in	O
+the	O
+orbicularis	O
+oculi	O
+muscle	O
+ipsilateral	O
+to	O
+the	O
+side	O
+of	O
+stimulation	O
+,	O
+a	O
+bilateral	O
+late	O
+response	O
+(	O
+ipsilateral	O
+R2	O
+and	O
+contralateral	O
+Rc	O
+)	O
+and	O
+a	O
+third	O
+,	O
+R3	O
+response	O
+,	O
+in	O
+the	O
+ipsilateral	O
+orbicularis	O
+oculi	O
+muscle	O
+.	O
+
+The	O
+prognosis	O
+of	O
+seven	O
+patients	O
+who	O
+received	O
+ABSCT	O
+was	O
+significantly	O
+better	O
+than	O
+that	O
+of	O
+13	O
+patients	O
+who	O
+received	O
+conventional	O
+therapy	O
+alone	O
+.	O
+
+(	O
+1994	O
+,	O
+Hum	O
+.	O
+
+The	O
+pigment	O
+intensity	O
+of	O
+both	O
+melanized	O
+colonies	O
+and	O
+appressoria	O
+of	O
+CAL	O
+transformants	O
+was	O
+weaker	O
+than	O
+that	O
+of	O
+the	O
+wild	O
+type	O
+.	O
+
+Malonate	O
+decarboxylation	O
+in	O
+Malonomonas	O
+rubra	O
+involves	O
+the	O
+formation	O
+of	O
+malonyl	B-GENE
+-	I-GENE
+S	I-GENE
+-	I-GENE
+[	I-GENE
+acyl	I-GENE
+-	I-GENE
+carrier	I-GENE
+protein	I-GENE
+]	I-GENE
+from	O
+acetyl	B-GENE
+-	I-GENE
+S	I-GENE
+-	I-GENE
+[	I-GENE
+acyl	I-GENE
+-	I-GENE
+carrier	I-GENE
+protein	I-GENE
+]	I-GENE
+and	O
+malonate	O
+,	O
+carboxyltransfer	O
+to	O
+a	O
+biotin	B-GENE
+protein	I-GENE
+and	O
+its	O
+decarboxylation	O
+that	O
+is	O
+coupled	O
+to	O
+delta	O
+mu	O
+Na	O
++	O
+generation	O
+.	O
+
+The	O
+Jem	B-GENE
+peptide	O
+sequence	O
+shows	O
+a	O
+'	O
+leucine	O
+-	O
+zipper	O
+'	O
+dimerisation	O
+motif	O
+with	O
+limited	O
+homology	O
+to	O
+Fos	B-GENE
+/	O
+Jun	B-GENE
+and	O
+ATF	B-GENE
+/	O
+CREB	B-GENE
+proteins	O
+and	O
+several	O
+putative	O
+phosphorylation	O
+sites	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+cloning	O
+of	O
+the	O
+protein	O
+that	O
+binds	O
+to	O
+enhancer	O
+site	O
+III	O
+.	O
+
+Further	O
+support	O
+for	O
+a	O
+direct	O
+interaction	O
+of	O
+Tub4p	B-GENE
+,	O
+Spc98p	B-GENE
+and	O
+Spc97p	B-GENE
+comes	O
+from	O
+the	O
+toxicity	O
+of	O
+strong	O
+SPC97	B-GENE
+overexpression	O
+which	O
+is	O
+suppressed	O
+by	O
+co	O
+-	O
+overexpression	O
+of	O
+TUB4	B-GENE
+or	O
+SPC98	B-GENE
+.	O
+
+Sequences	O
+needed	O
+for	O
+iron	O
+-	O
+regulated	O
+expression	O
+of	O
+sid1	B-GENE
+were	O
+localized	O
+to	O
+a	O
+306	O
+bp	O
+region	O
+mapping	O
+2	O
+.	O
+3	O
+and	O
+2	O
+.	O
+6	O
+kb	O
+upstream	O
+of	O
+the	O
+ATG	O
+.	O
+
+Comparison	O
+of	O
+the	O
+p50	B-GENE
+sequence	I-GENE
+to	O
+other	O
+cloned	O
+proteins	O
+revealed	O
+89	O
+%	O
+homology	O
+with	O
+a	O
+glycosaminoglycan	O
+-	O
+binding	O
+protein	O
+and	O
+54	O
+%	O
+homology	O
+with	O
+Drosophila	B-GENE
+cell	I-GENE
+cycle	I-GENE
+control	I-GENE
+protein	I-GENE
+(	I-GENE
+cdc	I-GENE
+)	I-GENE
+37	O
+.	O
+
+Additional	O
+information	O
+including	O
+echocardiographic	O
+sequences	O
+,	O
+perioperative	O
+video	O
+sequences	O
+,	O
+x	O
+-	O
+ray	O
+analysis	O
+,	O
+angiograms	O
+,	O
+etc	O
+.	O
+is	O
+represented	O
+in	O
+the	O
+program	O
+.	O
+
+We	O
+report	O
+here	O
+that	O
+constitutively	O
+active	O
+Mek1	B-GENE
+could	O
+activate	O
+p96h2bk	B-GENE
+in	O
+the	O
+absence	O
+of	O
+oncogenic	B-GENE
+Ras	I-GENE
+.	O
+
+In	O
+Schizosaccharomyces	O
+pombe	O
+,	O
+the	O
+activity	O
+of	O
+the	O
+M	O
+-	O
+phase	O
+-	O
+inducing	O
+Cdc2	B-GENE
+/	O
+Cdc13	B-GENE
+cyclin	O
+-	O
+dependent	O
+kinase	O
+is	O
+inhibited	O
+by	O
+Wee1	B-GENE
+and	O
+Mik1	B-GENE
+tyrosine	B-GENE
+kinases	I-GENE
+,	O
+and	O
+activated	O
+by	O
+Cdc25	B-GENE
+and	O
+Pyp3	B-GENE
+tyrosine	B-GENE
+phosphatases	I-GENE
+.	O
+
+The	O
+sequencing	O
+of	O
+Stellate	B-GENE
+copies	O
+located	O
+along	O
+the	O
+discontinuous	O
+cluster	O
+revealed	O
+a	O
+complex	O
+pattern	O
+of	O
+diversification	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+DNA	O
+methylation	O
+,	O
+chromatin	O
+structure	O
+,	O
+and	O
+transactivation	O
+at	O
+an	O
+Sp1	B-GENE
+site	I-GENE
+contribute	O
+to	O
+the	O
+highly	O
+restricted	O
+expression	O
+of	O
+this	O
+myelomonocytic	O
+lineage	O
+specific	O
+gene	O
+.	O
+
+In	O
+gel	O
+mobility	O
+shift	O
+assays	O
+,	O
+factors	O
+present	O
+in	O
+nuclear	O
+extracts	O
+derived	O
+from	O
+differentiated	O
+osteoblast	O
+bound	O
+to	O
+oligonucleotide	O
+probes	O
+containing	O
+the	O
+E	O
+-	O
+box	O
+1	O
+and	O
+E	O
+-	O
+box	O
+2	O
+elements	O
+.	O
+
+Laboratory	O
+exam	O
+:	O
+IDR	O
+of	O
+the	O
+tuberculin	B-GENE
+was	O
+high	O
+positive	O
+,	O
+chest	O
+radiography	O
+shows	O
+hilar	O
+bilateral	O
+calcifications	O
+,	O
+ORL	O
+exam	O
+shows	O
+a	O
+tumor	O
+at	O
+the	O
+foot	O
+of	O
+the	O
+epiglottis	O
+and	O
+anatomopathological	O
+exam	O
+shows	O
+low	O
+differentiated	O
+epidermoid	O
+carcinoma	O
+.	O
+
+Finally	O
+,	O
+we	O
+show	O
+that	O
+PhLP	B-GENE
+complexes	O
+,	O
+at	O
+least	O
+partially	O
+,	O
+with	O
+Gbetagamma	B-GENE
+in	O
+vivo	O
+.	O
+
+CTF1alpha	B-GENE
+,	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+,	O
+showed	O
+specific	O
+binding	O
+to	O
+the	O
+palindrome	O
+2	O
+DNA	O
+fragment	O
+but	O
+not	O
+to	O
+palindrome	O
+1	O
+or	O
+mutant	O
+palindrome	O
+2	O
+DNA	O
+fragments	O
+,	O
+suggesting	O
+specific	O
+binding	O
+of	O
+CTF1alpha	B-GENE
+to	O
+palindrome	O
+2	O
+.	O
+
+Cyclin	B-GENE
+G2	I-GENE
+is	O
+highly	O
+expressed	O
+in	O
+the	O
+immune	O
+system	O
+where	O
+immunologic	O
+tolerance	O
+subjects	O
+self	O
+-	O
+reactive	O
+lymphocytes	O
+to	O
+negative	O
+selection	O
+and	O
+clonal	O
+deletion	O
+via	O
+apoptosis	O
+.	O
+
+A	O
+sterol	O
+-	O
+regulated	O
+protease	O
+initiates	O
+release	O
+of	O
+the	O
+NH2	O
+-	O
+terminal	O
+segments	O
+of	O
+sterol	B-GENE
+regulatory	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+(	O
+SREBPs	B-GENE
+)	O
+from	O
+cell	O
+membranes	O
+,	O
+thereby	O
+allowing	O
+them	O
+to	O
+enter	O
+the	O
+nucleus	O
+and	O
+to	O
+stimulate	O
+transcription	O
+of	O
+genes	O
+involved	O
+in	O
+the	O
+uptake	O
+and	O
+synthesis	O
+of	O
+cholesterol	O
+and	O
+fatty	O
+acids	O
+.	O
+
+Thus	O
+,	O
+the	O
+P	O
+.	O
+aeruginosa	O
+orfX	O
+and	O
+vfr	B-GENE
+promoters	I-GENE
+are	O
+arranged	O
+in	O
+a	O
+back	O
+-	O
+to	O
+-	O
+back	O
+orientation	O
+rather	O
+than	O
+the	O
+face	O
+-	O
+to	O
+-	O
+face	O
+orientation	O
+of	O
+the	O
+dorf	O
+and	O
+crp	B-GENE
+promoters	I-GENE
+.	O
+
+Sequence	O
+analysis	O
+of	O
+cloned	O
+PCR	O
+products	O
+confirmed	O
+the	O
+presence	O
+of	O
+two	O
+different	O
+nifV	B-GENE
+-	I-GENE
+like	I-GENE
+DNA	I-GENE
+fragments	I-GENE
+,	O
+which	O
+were	O
+subsequently	O
+used	O
+as	O
+nifV	B-GENE
+-	O
+and	O
+leuA	B-GENE
+-	I-GENE
+specific	I-GENE
+probes	I-GENE
+,	O
+respectively	O
+,	O
+to	O
+clone	O
+XbaI	B-GENE
+fragments	I-GENE
+of	O
+2	O
+.	O
+1	O
+kbp	O
+(	O
+pOST4	O
+)	O
+and	O
+2	O
+.	O
+6	O
+kbp	O
+(	O
+pOST2	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+Anabaena	O
+strain	O
+7120	O
+leuA	B-GENE
+gene	O
+did	O
+not	O
+complement	O
+the	O
+nifV	B-GENE
+mutation	I-GENE
+of	O
+R229I	O
+efficiently	O
+.	O
+
+(	O
+3	O
+)	O
+This	O
+effect	O
+occurs	O
+without	O
+removing	O
+TRs	B-GENE
+from	O
+the	O
+TRE	O
+.	O
+
+In	O
+a	O
+model	O
+of	O
+the	O
+ternary	O
+complex	O
+,	O
+the	O
+segment	O
+of	O
+NFAT	B-GENE
+nearest	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+the	O
+Rel	B-GENE
+insert	O
+region	O
+(	O
+RIR	O
+)	O
+,	O
+a	O
+feature	O
+that	O
+is	O
+notable	O
+for	O
+its	O
+hypervariability	O
+in	O
+size	O
+and	O
+in	O
+sequence	O
+amongst	O
+members	O
+of	O
+the	O
+Rel	B-GENE
+transcription	I-GENE
+factor	I-GENE
+family	I-GENE
+.	O
+
+We	O
+thus	O
+conclude	O
+that	O
+the	O
+NFAT	B-GENE
+RIR	I-GENE
+plays	O
+an	O
+essential	O
+dual	O
+role	O
+in	O
+DNA	O
+recognition	O
+and	O
+cooperative	O
+binding	O
+to	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+family	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+association	O
+of	O
+PS1	B-GENE
+fragments	I-GENE
+may	O
+be	O
+maintained	O
+during	O
+cycles	O
+of	O
+phosphorylation	O
+/	O
+dephosphorylation	O
+of	O
+the	O
+PS1	B-GENE
+CTF	I-GENE
+.	O
+
+This	O
+protein	O
+can	O
+bind	O
+to	O
+a	O
+region	O
+of	O
+the	O
+promoter	O
+of	O
+an	O
+Arabidopsis	B-GENE
+light	I-GENE
+-	I-GENE
+harvesting	I-GENE
+chlorophyll	I-GENE
+a	I-GENE
+/	I-GENE
+b	I-GENE
+protein	I-GENE
+gene	I-GENE
+,	O
+Lhcb1	B-GENE
+*	I-GENE
+3	I-GENE
+,	O
+which	O
+is	O
+necessary	O
+for	O
+its	O
+regulation	O
+by	O
+phytochrome	B-GENE
+.	O
+
+A	O
+patient	O
+of	O
+Group	O
+B	O
+had	O
+severe	O
+athetoid	O
+CP	O
+with	O
+spasticity	O
+,	O
+being	O
+unable	O
+to	O
+right	O
+his	O
+trunk	O
+and	O
+neck	O
+.	O
+
+Dystonic	O
+movement	O
+of	O
+the	O
+left	O
+upper	O
+limb	O
+in	O
+a	O
+case	O
+of	O
+the	O
+right	O
+pontine	O
+hemorrhage	O
+
+It	O
+has	O
+repeatedly	O
+been	O
+shown	O
+that	O
+HCMV	O
+IE1	B-GENE
+/	O
+IE2	B-GENE
+can	O
+independently	O
+transactivate	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+LTR	I-GENE
+.	O
+
+TAR	B-GENE
+and	O
+Sp1	B-GENE
+-	O
+independent	O
+transactivation	O
+of	O
+HIV	B-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+by	O
+the	O
+Tat	B-GENE
+protein	I-GENE
+in	O
+the	O
+presence	O
+of	O
+human	O
+cytomegalovirus	O
+IE1	B-GENE
+/	O
+IE2	B-GENE
+.	O
+
+Respiratory	O
+chain	O
+enzyme	O
+activity	O
+was	O
+normal	O
+.	O
+
+Cellular	B-GENE
+Csk	I-GENE
+was	O
+associated	O
+with	O
+several	O
+phosphoproteins	O
+,	O
+some	O
+of	O
+which	O
+were	O
+interacting	O
+with	O
+the	O
+Csk	B-GENE
+SH2	B-GENE
+domain	I-GENE
+.	O
+
+Thus	O
+,	O
+our	O
+studies	O
+suggest	O
+that	O
+pV	O
+-	O
+mediated	O
+activation	O
+of	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+LTR	I-GENE
+activity	O
+is	O
+controlled	O
+by	O
+the	O
+nuclear	O
+translocation	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+transcription	I-GENE
+factor	I-GENE
+,	O
+which	O
+is	O
+mediated	O
+by	O
+IkappaBalpha	B-GENE
+serine	O
+phosphorylation	O
+and	O
+degradation	O
+,	O
+but	O
+also	O
+by	O
+a	O
+still	O
+undefined	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+-	O
+independent	O
+pathway	O
+.	O
+
+FN	B-GENE
+-	O
+stimulated	O
+c	B-GENE
+-	I-GENE
+Src	I-GENE
+PTK	B-GENE
+activity	O
+was	O
+enhanced	O
+by	O
+wild	O
+type	O
+FAK	B-GENE
+expression	O
+,	O
+whereas	O
+FN	B-GENE
+-	O
+stimulated	O
+activation	O
+of	O
+ERK2	B-GENE
+was	O
+blocked	O
+by	O
+expression	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+Src	I-GENE
+binding	I-GENE
+site	I-GENE
+Phe	I-GENE
+-	I-GENE
+397	I-GENE
+mutant	I-GENE
+of	O
+FAK	B-GENE
+.	O
+
+A	O
+promising	O
+new	O
+cement	O
+,	O
+4	O
+-	O
+META	O
+/	O
+MMA	O
+-	O
+TBB	O
+opaque	O
+resin	O
+,	O
+has	O
+shown	O
+remarkable	O
+adhesive	O
+properties	O
+as	O
+a	O
+bone	O
+cement	O
+in	O
+vivo	O
+.	O
+
+Each	O
+sample	O
+was	O
+analysed	O
+as	O
+soon	O
+as	O
+possible	O
+,	O
+and	O
+repeated	O
+15	O
+,	O
+30	O
+,	O
+60	O
+and	O
+120	O
+min	O
+after	O
+sampling	O
+.	O
+
+Like	O
+the	O
+elicitors	O
+of	O
+the	O
+hypersensitive	O
+reaction	O
+(	O
+HR	O
+)	O
+produced	O
+by	O
+E	O
+.	O
+chrysanthemi	O
+(	O
+HarpinEch	O
+)	O
+and	O
+E	O
+.	O
+amylovora	O
+(	O
+HarpinEa	O
+)	O
+,	O
+the	O
+deduced	O
+36	O
+-	O
+kDa	O
+protein	O
+does	O
+not	O
+possess	O
+a	O
+typical	O
+signal	O
+sequence	O
+,	O
+but	O
+it	O
+contains	O
+a	O
+putative	O
+membrane	O
+-	O
+spanning	O
+domain	O
+.	O
+
+Molecular	O
+characterization	O
+and	O
+expression	O
+of	O
+the	O
+Erwinia	B-GENE
+carotovora	I-GENE
+hrpNEcc	I-GENE
+gene	I-GENE
+,	O
+which	O
+encodes	O
+an	O
+elicitor	O
+of	O
+the	O
+hypersensitive	O
+reaction	O
+.	O
+
+The	O
+mRNA	O
+from	O
+this	O
+gene	O
+,	O
+termed	O
+HES1	B-GENE
+,	O
+is	O
+ubiquitously	O
+expressed	O
+,	O
+but	O
+strongly	O
+so	O
+in	O
+heart	O
+and	O
+skeletal	O
+muscle	O
+.	O
+
+Anesthesia	O
+was	O
+maintained	O
+with	O
+isoflurane	O
+(	O
+ISO	O
+)	O
+/	O
+N2O	O
+/	O
+O2	O
+inhalation	O
+.	O
+
+They	O
+observed	O
+depressed	O
+protein	B-GENE
+C	I-GENE
+activity	O
+that	O
+significantly	O
+(	O
+p	O
+<	O
+0	O
+.	O
+005	O
+)	O
+increased	O
+and	O
+became	O
+normal	O
+immediately	O
+after	O
+hemodialysis	O
+while	O
+factor	B-GENE
+X	I-GENE
+and	O
+factor	B-GENE
+VII	I-GENE
+increased	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+;	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+despite	O
+heparinization	O
+together	O
+with	O
+amount	O
+of	O
+serum	B-GENE
+lipoprotein	I-GENE
+(	I-GENE
+a	I-GENE
+)	I-GENE
+.	O
+
+We	O
+present	O
+a	O
+case	O
+of	O
+type	O
+II	O
+hyperbetalipoproteinemia	O
+in	O
+a	O
+patient	O
+whose	O
+diagnosis	O
+had	O
+been	O
+previously	O
+unrecognized	O
+,	O
+and	O
+who	O
+had	O
+previously	O
+been	O
+misdiagnosed	O
+with	O
+rheumatoid	O
+arthritis	O
+and	O
+later	O
+gout	O
+.	O
+
+These	O
+data	O
+provide	O
+evidence	O
+that	O
+the	O
+2	B-GENE
+.	I-GENE
+0	I-GENE
+-	I-GENE
+kb	I-GENE
+LAT	I-GENE
+is	O
+an	O
+intron	O
+of	O
+the	O
+mLAT	B-GENE
+pre	I-GENE
+-	I-GENE
+mRNA	I-GENE
+with	O
+a	O
+unique	O
+branch	O
+point	O
+.	O
+
+The	O
+altered	O
+amino	O
+acid	O
+residues	O
+of	O
+the	O
+seven	O
+mutant	B-GENE
+9ORF1	I-GENE
+polypeptides	I-GENE
+clustered	O
+within	O
+three	O
+separate	O
+regions	O
+referred	O
+to	O
+as	O
+region	O
+I	O
+(	O
+residues	O
+34	O
+to	O
+41	O
+)	O
+,	O
+region	O
+II	O
+(	O
+residues	O
+89	O
+to	O
+91	O
+)	O
+,	O
+and	O
+C	O
+-	O
+terminal	O
+region	O
+III	O
+(	O
+residues	O
+122	O
+to	O
+125	O
+)	O
+.	O
+
+Rep	B-GENE
+-	O
+Rep	B-GENE
+protein	O
+interaction	O
+was	O
+confirmed	O
+in	O
+vitro	O
+through	O
+coimmunoprecipitation	O
+experiments	O
+with	O
+a	O
+bacterially	O
+expressed	O
+maltose	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+-	O
+Rep78	B-GENE
+fusion	O
+protein	O
+in	O
+combination	O
+with	O
+[	O
+35S	O
+]	O
+methionine	O
+-	O
+labeled	O
+Rep78	B-GENE
+synthesized	O
+in	O
+a	O
+coupled	O
+in	O
+vitro	O
+transcription	O
+-	O
+translation	O
+system	O
+.	O
+
+Fourteen	O
+patients	O
+with	O
+New	O
+York	O
+Heart	O
+Association	O
+class	O
+II	O
+congestive	O
+heart	O
+failure	O
+were	O
+enrolled	O
+in	O
+a	O
+double	O
+-	O
+blind	O
+,	O
+cross	O
+-	O
+over	O
+study	O
+.	O
+
+The	O
+main	O
+advantages	O
+of	O
+Multi	O
+-	O
+MUP	O
+analysis	O
+are	O
+:	O
+(	O
+1	O
+)	O
+quick	O
+acquisition	O
+of	O
+many	O
+MUPs	O
+;	O
+(	O
+2	O
+)	O
+simultaneous	O
+collection	O
+of	O
+several	O
+MUPs	O
+at	O
+one	O
+recording	O
+site	O
+;	O
+(	O
+3	O
+)	O
+possibility	O
+to	O
+analyze	O
+not	O
+only	O
+low	O
+threshold	O
+MUPs	O
+;	O
+(	O
+4	O
+)	O
+less	O
+bias	O
+in	O
+the	O
+selection	O
+of	O
+MUPs	O
+and	O
+(	O
+5	O
+)	O
+the	O
+reproducibility	O
+of	O
+the	O
+results	O
+that	O
+allow	O
+the	O
+same	O
+reference	O
+values	O
+to	O
+be	O
+used	O
+in	O
+different	O
+laboratories	O
+.	O
+
+In	O
+several	O
+studies	O
+the	O
+RDFS	O
+has	O
+shown	O
+evidence	O
+of	O
+reliability	O
+and	O
+validity	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+dietary	O
+safflower	O
+phospholipids	O
+may	O
+be	O
+a	O
+valuable	O
+ingredient	O
+to	O
+layers	O
+for	O
+reducing	O
+liver	O
+triglycerides	O
+and	O
+serum	O
+cholesterol	O
+without	O
+any	O
+adverse	O
+effects	O
+.	O
+
+Using	O
+various	O
+techniques	O
+,	O
+we	O
+have	O
+undertaken	O
+a	O
+systematic	O
+analysis	O
+of	O
+the	O
+natural	O
+TATA	O
+-	O
+less	O
+human	B-GENE
+DNA	I-GENE
+polymerase	I-GENE
+beta	I-GENE
+(	O
+beta	B-GENE
+-	I-GENE
+pol	I-GENE
+)	O
+gene	O
+promoter	O
+.	O
+
+Saturable	O
+spermidine	O
+transport	O
+in	O
+stk2	B-GENE
+:	O
+:	O
+lacZ	B-GENE
+mutants	I-GENE
+had	O
+an	O
+approximately	O
+fivefold	O
+-	O
+lower	O
+affinity	O
+and	O
+twofold	O
+-	O
+lower	O
+Vmax	O
+than	O
+in	O
+the	O
+parental	O
+strain	O
+.	O
+
+Inhibition	O
+of	O
+the	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+kinase	I-GENE
+by	O
+cyclic	O
+AMP	O
+agonists	O
+causes	O
+apoptosis	O
+of	O
+v	B-GENE
+-	I-GENE
+abl	I-GENE
+-	O
+transformed	O
+cells	O
+.	O
+
+Previous	O
+studies	O
+have	O
+indicated	O
+that	O
+a	O
+hamster	O
+cell	O
+line	O
+(	O
+ts13	O
+)	O
+with	O
+a	O
+point	O
+mutation	O
+in	O
+the	O
+TAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+250	I-GENE
+/	O
+CCG1	B-GENE
+(	O
+TAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+250	I-GENE
+)	O
+gene	O
+shows	O
+temperature	O
+-	O
+sensitive	O
+expression	O
+of	O
+a	O
+subset	O
+of	O
+genes	O
+and	O
+arrests	O
+in	O
+late	O
+G1	O
+at	O
+39	O
+.	O
+5	O
+degrees	O
+C	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+the	O
+protein	O
+kinase	O
+MEKK1	B-GENE
+can	O
+induce	O
+reporter	O
+gene	O
+expression	O
+from	O
+the	O
+atrial	B-GENE
+natriuretic	I-GENE
+factor	I-GENE
+(	O
+ANF	B-GENE
+)	O
+promoter	O
+,	O
+a	O
+genetic	O
+marker	O
+that	O
+is	O
+activated	O
+during	O
+in	O
+vivo	O
+hypertrophy	O
+.	O
+
+Overexpression	O
+of	O
+EFG1	B-GENE
+in	O
+C	O
+.	O
+albicans	O
+leads	O
+to	O
+enhanced	O
+filamentous	O
+growth	O
+in	O
+the	O
+form	O
+of	O
+extended	O
+pseudohyphae	O
+in	O
+liquid	O
+and	O
+on	O
+solid	O
+media	O
+.	O
+
+To	O
+determine	O
+if	O
+signing	O
+,	O
+when	O
+established	O
+,	O
+would	O
+compete	O
+with	O
+SIB	O
+when	O
+both	O
+were	O
+reinforced	O
+,	O
+extinction	O
+was	O
+then	O
+withdrawn	O
+.	O
+
+The	O
+husband	O
+in	O
+one	O
+of	O
+the	O
+married	O
+couples	O
+was	O
+treated	O
+for	O
+hepatitis	O
+of	O
+unidentified	O
+etiology	O
+in	O
+an	O
+Infectology	O
+Department	O
+four	O
+years	O
+ago	O
+.	O
+
+Both	O
+quantitative	O
+and	O
+qualitative	O
+analysis	O
+of	O
+individual	O
+cytoarchitectonic	O
+peculiarities	O
+of	O
+Meynart	O
+'	O
+s	O
+nucleus	O
+as	O
+well	O
+as	O
+of	O
+external	O
+part	O
+of	O
+dorsomedial	O
+nucleus	O
+of	O
+thalamus	O
+was	O
+performed	O
+in	O
+mentally	O
+normal	O
+individuals	O
+.	O
+
+Positional	O
+cloning	O
+has	O
+already	O
+produced	O
+the	O
+sequences	O
+of	O
+more	O
+than	O
+70	O
+human	O
+genes	O
+associated	O
+with	O
+specific	O
+diseases	O
+.	O
+
+The	O
+30	O
+-	O
+day	O
+mortality	O
+in	O
+the	O
+CPB	O
+group	O
+and	O
+the	O
+non	O
+-	O
+CPB	O
+group	O
+were	O
+20	O
+%	O
+and	O
+4	O
+.	O
+6	O
+%	O
+,	O
+respectively	O
+which	O
+was	O
+not	O
+statistically	O
+significant	O
+(	O
+p	O
+=	O
+0	O
+.	O
+06	O
+)	O
+.	O
+
+As	O
+opposed	O
+to	O
+in	O
+vitro	O
+co	O
+-	O
+precipitation	O
+studies	O
+,	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+screen	O
+reveals	O
+in	O
+vivo	O
+protein	O
+-	O
+protein	O
+interactions	O
+.	O
+
+This	O
+association	O
+appears	O
+to	O
+be	O
+mediated	O
+by	O
+Src	B-GENE
+-	O
+SH2	B-GENE
+domain	O
+,	O
+because	O
+PECAM	B-GENE
+-	I-GENE
+1	I-GENE
+can	O
+be	O
+precipitated	O
+by	O
+a	O
+GST	B-GENE
+-	O
+Src	B-GENE
+-	O
+SH2	B-GENE
+affinity	O
+matrix	O
+.	O
+
+MKK3	B-GENE
+autophosphorylation	O
+and	O
+activation	O
+of	O
+p38	B-GENE
+was	O
+also	O
+observed	O
+following	O
+coexpression	O
+of	O
+MKK3	B-GENE
+with	O
+MEKK3	B-GENE
+,	O
+but	O
+not	O
+with	O
+MEKK2	B-GENE
+.	O
+
+An	O
+alternatively	O
+spliced	O
+MAdCAM	B-GENE
+-	I-GENE
+1	I-GENE
+variant	O
+was	O
+identified	O
+that	O
+lacks	O
+exon	O
+4	O
+encoding	O
+the	O
+mucin	B-GENE
+domain	O
+,	O
+and	O
+may	O
+mediate	O
+leukocyte	O
+adhesion	O
+to	O
+LPAM	B-GENE
+-	I-GENE
+1	I-GENE
+without	O
+adhesion	O
+to	O
+the	O
+alternate	O
+receptor	O
+,	O
+L	B-GENE
+-	I-GENE
+selectin	I-GENE
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+data	O
+establish	O
+that	O
+the	O
+previously	O
+reported	O
+human	B-GENE
+MAdCAM	I-GENE
+-	I-GENE
+1	I-GENE
+cDNA	I-GENE
+does	O
+indeed	O
+encode	O
+the	O
+human	O
+homologue	O
+of	O
+mouse	B-GENE
+MAdCAM	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+despite	O
+gross	O
+dissimilarities	O
+in	O
+the	O
+MAdCAM	B-GENE
+-	I-GENE
+1	I-GENE
+C	O
+-	O
+terminal	O
+structures	O
+.	O
+
+We	O
+have	O
+used	O
+a	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+approach	O
+to	O
+examine	O
+how	O
+the	O
+Xaa	O
+and	O
+hydroxy	O
+(	O
+Ser	O
+/	O
+Thr	O
+)	O
+amino	O
+acid	O
+residues	O
+in	O
+sequons	O
+influence	O
+core	O
+-	O
+glycosylation	O
+efficiency	O
+.	O
+
+MATERIAL	O
+AND	O
+METHODS	O
+:	O
+The	O
+authors	O
+analyzed	O
+41	O
+persons	O
+formerly	O
+submitted	O
+to	O
+surgery	O
+(	O
+after	O
+8	O
+years	O
+and	O
+4	O
+months	O
+,	O
+as	O
+a	O
+mean	O
+)	O
+,	O
+31	O
+to	O
+highly	O
+selective	O
+vagotomy	O
+,	O
+and	O
+10	O
+to	O
+truncal	O
+or	O
+selective	O
+vagotomy	O
+plus	O
+gastroduodenal	O
+drainage	O
+.	O
+
+This	O
+region	O
+does	O
+not	O
+contain	O
+an	O
+identifiable	O
+TATA	O
+element	O
+,	O
+indicating	O
+that	O
+transcription	O
+of	O
+the	O
+glutaminase	B-GENE
+gene	I-GENE
+is	O
+driven	O
+by	O
+a	O
+TATA	O
+-	O
+less	O
+promoter	O
+.	O
+
+Serum	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+activity	O
+,	O
+bone	O
+mass	O
+measurements	O
+,	O
+dual	O
+energy	O
+x	O
+-	O
+ray	O
+absortiometric	O
+analysis	O
+of	O
+mineral	O
+density	O
+,	O
+and	O
+mechanical	O
+testing	O
+values	O
+in	O
+vertebrae	O
+and	O
+femora	O
+of	O
+the	O
+-	O
+D	O
+Sal	O
+animals	O
+did	O
+not	O
+significantly	O
+differ	O
+from	O
+those	O
+in	O
++	O
+D	O
+Sal	O
+animals	O
+.	O
+
+The	O
+monkey	B-GENE
+LHR	I-GENE
+cDNA	I-GENE
+displayed	O
+83	O
+-	O
+94	O
+%	O
+overall	O
+sequence	O
+homology	O
+with	O
+the	O
+other	O
+mammalian	B-GENE
+LHR	I-GENE
+cDNAs	I-GENE
+.	O
+
+In	O
+conclusion	O
+,	O
+marmoset	B-GENE
+monkey	I-GENE
+LHR	I-GENE
+seems	O
+to	O
+lack	O
+the	O
+sequence	O
+corresponding	O
+to	O
+exon	O
+10	O
+of	O
+the	O
+LHR	B-GENE
+gene	I-GENE
+in	O
+other	O
+mammalian	O
+species	O
+.	O
+
+In	O
+unc	B-GENE
+-	I-GENE
+4	I-GENE
+mutants	I-GENE
+,	O
+VA	O
+motor	O
+neurons	O
+assume	O
+the	O
+pattern	O
+of	O
+synaptic	O
+input	O
+normally	O
+reserved	O
+for	O
+their	O
+lineal	O
+sister	O
+cells	O
+,	O
+the	O
+VB	O
+motor	O
+neurons	O
+;	O
+the	O
+loss	O
+of	O
+normal	O
+input	O
+to	O
+the	O
+VAs	O
+produces	O
+a	O
+distinctive	O
+backward	O
+movement	O
+defect	O
+.	O
+
+Intracavitary	O
+irradiation	O
+was	O
+carried	O
+out	O
+with	O
+a	O
+microSelectron	O
+HDR	O
+afterloading	O
+device	O
+and	O
+usually	O
+22	O
+.	O
+5	O
+Gy	O
+was	O
+given	O
+in	O
+three	O
+fractions	O
+repeated	O
+weekly	O
+.	O
+
+No	O
+patient	O
+in	O
+group	O
+2	O
+developed	O
+HAT	O
+(	O
+P	O
+=	O
+0	O
+.	O
+006	O
+versus	O
+group	O
+1	O
+)	O
+.	O
+
+Sequence	O
+comparison	O
+of	O
+the	O
+0	O
+.	O
+38	O
+kb	O
+promoter	O
+sequence	O
+with	O
+the	O
+promoters	O
+of	O
+the	O
+Sm	B-GENE
+-	I-GENE
+E	I-GENE
+gene	O
+and	O
+U1	B-GENE
+snRNA	I-GENE
+genes	I-GENE
+revealed	O
+several	O
+homologous	O
+motifs	O
+,	O
+suggesting	O
+that	O
+genes	O
+encoding	O
+the	O
+snRNP	O
+components	O
+may	O
+be	O
+coordinately	O
+regulated	O
+.	O
+
+METHODS	O
+:	O
+The	O
+responses	O
+of	O
+a	O
+31	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+complex	O
+regional	O
+pain	O
+syndrome	O
+type	O
+I	O
+(	O
+reflex	O
+sympathetic	O
+dystrophy	O
+)	O
+to	O
+a	O
+thermal	O
+grill	O
+were	O
+evaluated	O
+before	O
+and	O
+after	O
+stellate	O
+ganglion	O
+block	O
+.	O
+
+More	O
+recently	O
+,	O
+however	O
+,	O
+a	O
+number	O
+of	O
+developments	O
+such	O
+as	O
+the	O
+successful	O
+use	O
+of	O
+the	O
+inhaled	O
+steroid	O
+budesonide	O
+and	O
+oral	O
+dexamethasone	O
+have	O
+reinforced	O
+the	O
+argument	O
+for	O
+using	O
+steroids	O
+.	O
+
+In	O
+AcMNPV	O
+-	O
+infected	O
+Sf9	O
+cells	O
+,	O
+late	O
+transcription	O
+initiation	O
+is	O
+detected	O
+from	O
+only	O
+two	O
+upstream	O
+TAAG	O
+sites	O
+and	O
+not	O
+from	O
+three	O
+downstream	O
+TAAG	O
+sites	O
+.	O
+
+Mutation	O
+of	O
+nucleotides	O
+adjacent	O
+to	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+cis	I-GENE
+-	I-GENE
+response	I-GENE
+elements	I-GENE
+had	O
+no	O
+effect	O
+on	O
+trans	O
+-	O
+activation	O
+.	O
+
+The	O
+close	O
+proximity	O
+of	O
+the	O
+two	O
+neuropeptide	B-GENE
+Y	I-GENE
+receptor	I-GENE
+genes	I-GENE
+suggests	O
+that	O
+they	O
+have	O
+evolved	O
+from	O
+a	O
+gene	O
+duplication	O
+event	O
+with	O
+the	O
+small	O
+intron	O
+interrupting	O
+the	O
+coding	O
+sequence	O
+of	O
+the	O
+y1	B-GENE
+gene	I-GENE
+being	O
+converted	O
+into	O
+a	O
+functional	O
+sequence	O
+within	O
+the	O
+y5	B-GENE
+gene	I-GENE
+,	O
+while	O
+the	O
+reverse	O
+complementary	O
+sequence	O
+was	O
+utilized	O
+as	O
+an	O
+alternatively	O
+spliced	O
+5	O
+'	O
+exon	O
+for	O
+the	O
+y1	B-GENE
+gene	I-GENE
+.	O
+
+The	O
+mammalian	B-GENE
+phosphoinositide	I-GENE
+3	I-GENE
+-	I-GENE
+kinases	I-GENE
+(	O
+PI3Ks	B-GENE
+)	O
+p110alpha	B-GENE
+,	I-GENE
+beta	I-GENE
+,	I-GENE
+and	I-GENE
+delta	I-GENE
+form	O
+heterodimers	O
+with	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+(	O
+SH2	B-GENE
+)	O
+domain	O
+-	O
+containing	O
+adaptors	O
+such	O
+as	O
+p85alpha	B-GENE
+or	O
+p55	B-GENE
+(	O
+PIK	B-GENE
+)	O
+.	O
+
+In	O
+the	O
+studies	O
+reported	O
+here	O
+,	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+gp130	I-GENE
+gene	I-GENE
+was	O
+isolated	O
+and	O
+the	O
+transcription	O
+initiation	O
+sites	O
+were	O
+mapped	O
+.	O
+
+Localization	O
+of	O
+the	O
+cytokine	O
+response	O
+element	O
+by	O
+5	O
+'	O
+-	O
+deletion	O
+analysis	O
+and	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+revealed	O
+a	O
+cis	O
+-	O
+acting	O
+binding	O
+site	O
+for	O
+activated	O
+STAT	B-GENE
+complexes	O
+.	O
+
+Insulin	B-GENE
+regulation	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+(	O
+MEK	B-GENE
+)	O
+,	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+and	O
+casein	B-GENE
+kinase	I-GENE
+in	O
+the	O
+cell	O
+nucleus	O
+:	O
+a	O
+possible	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+gene	O
+expression	O
+.	O
+
+Sequencing	O
+of	O
+the	O
+three	O
+pag	B-GENE
+-	I-GENE
+3	I-GENE
+alleles	I-GENE
+showed	O
+that	O
+two	O
+apparent	O
+null	O
+alleles	O
+encode	O
+a	O
+nonsense	O
+mutation	O
+before	O
+the	O
+zinc	O
+fingers	O
+and	O
+a	O
+missense	O
+mutation	O
+in	O
+the	O
+fourth	O
+zinc	O
+finger	O
+that	O
+changes	O
+a	O
+coordinating	O
+histidine	O
+to	O
+a	O
+tyrosine	O
+.	O
+
+Here	O
+,	O
+a	O
+case	O
+of	O
+Sjogren	O
+'	O
+s	O
+syndrome	O
+is	O
+presented	O
+that	O
+was	O
+initially	O
+diagnosed	O
+because	O
+of	O
+dental	O
+complaints	O
+,	O
+and	O
+long	O
+-	O
+term	O
+treatment	O
+of	O
+Sjogren	O
+'	O
+s	O
+patients	O
+is	O
+discussed	O
+.	O
+
+Cloning	O
+and	O
+characterization	O
+of	O
+a	O
+cDNA	O
+encoding	O
+a	O
+bacteriophage	B-GENE
+-	I-GENE
+type	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+from	O
+the	O
+higher	O
+plant	O
+Chenopodium	O
+album	O
+.	O
+
+Similarly	O
+,	O
+overexpression	O
+of	O
+increasing	O
+concentration	O
+of	O
+COUP	B-GENE
+-	I-GENE
+TFI	I-GENE
+,	O
+but	O
+not	O
+COUP	B-GENE
+-	I-GENE
+TFI	I-GENE
+delta35	I-GENE
+,	O
+can	O
+squelch	O
+the	O
+silencing	O
+activity	O
+of	O
+the	O
+unliganded	O
+TRbeta	B-GENE
+.	O
+
+In	O
+ciliates	O
+,	O
+both	O
+mechanisms	O
+are	O
+readily	O
+observed	O
+.	O
+
+Based	O
+on	O
+the	O
+occurrence	O
+of	O
+several	O
+transcription	O
+signals	O
+in	O
+the	O
+Thermus	B-GENE
+pyr	I-GENE
+promoter	I-GENE
+region	I-GENE
+and	O
+strong	O
+amino	O
+acid	O
+sequence	O
+identities	O
+(	O
+about	O
+60	O
+%	O
+)	O
+between	O
+Thermus	B-GENE
+PyrR	I-GENE
+and	O
+the	O
+PyrR	B-GENE
+attenuation	I-GENE
+proteins	I-GENE
+of	O
+two	O
+Bacillus	O
+sp	O
+.	O
+,	O
+we	O
+propose	O
+a	O
+regulatory	O
+mechanism	O
+involving	O
+transcriptional	O
+attenuation	O
+to	O
+control	O
+pyr	B-GENE
+gene	I-GENE
+expression	O
+in	O
+Thermus	O
+.	O
+
+Diver	O
+respiratory	O
+responses	O
+to	O
+a	O
+tunable	O
+closed	O
+-	O
+circuit	O
+breathing	O
+apparatus	O
+.	O
+
+Measurement	O
+of	O
+the	O
+time	O
+constant	O
+of	O
+VO2	O
+and	O
+oxygen	O
+pulse	O
+during	O
+constant	O
+work	O
+rate	O
+exercise	O
+are	O
+useful	O
+for	O
+the	O
+objective	O
+evaluation	O
+of	O
+the	O
+training	O
+effect	O
+of	O
+patients	O
+with	O
+COPD	O
+.	O
+
+Characterization	O
+of	O
+CR1	B-GENE
+repeat	O
+random	O
+PCR	O
+markers	O
+for	O
+mapping	O
+the	O
+chicken	O
+genome	O
+.	O
+
+A	O
+reversed	O
+-	O
+phase	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatographic	O
+(	O
+HPLC	O
+)	O
+method	O
+for	O
+the	O
+determination	O
+of	O
+cocaine	O
+metabolites	O
+produced	O
+in	O
+vitro	O
+by	O
+serum	B-GENE
+and	I-GENE
+liver	I-GENE
+esterases	I-GENE
+is	O
+described	O
+.	O
+
+Mutational	O
+studies	O
+provide	O
+evidence	O
+to	O
+this	O
+end	O
+and	O
+indicate	O
+that	O
+the	O
+side	O
+chains	O
+of	O
+subdomain	O
+4	O
+.	O
+2	O
+make	O
+specific	O
+contacts	O
+with	O
+the	O
+nucleotides	O
+at	O
+-	O
+35	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+fludarabine	O
+is	O
+a	O
+highly	O
+useful	O
+agent	O
+in	O
+CLL	O
+.	O
+
+Three	O
+different	O
+techniques	O
+of	O
+EA	O
+analysis	O
+were	O
+used	O
+in	O
+the	O
+study	O
+:	O
+1	O
+)	O
+fast	O
+Fourier	O
+transformation	O
+(	O
+FFT	O
+)	O
+of	O
+EA	O
+in	O
+a	O
+broad	O
+band	O
+,	O
+2	O
+)	O
+developed	O
+by	O
+us	O
+alternative	O
+method	O
+of	O
+non	O
+-	O
+harmonic	O
+expansion	O
+of	O
+the	O
+EEG	O
+curves	O
+taking	O
+into	O
+account	O
+their	O
+shape	O
+,	O
+3	O
+)	O
+factor	O
+analysis	O
+of	O
+the	O
+EA	O
+spectral	O
+densities	O
+.	O
+
+Concomitantly	O
+,	O
+p34CDC2	B-GENE
+histone	B-GENE
+H1	I-GENE
+kinase	O
+activity	O
+increases	O
+in	O
+the	O
+former	O
+,	O
+but	O
+not	O
+in	O
+the	O
+latter	O
+cell	O
+lines	O
+,	O
+hence	O
+suggesting	O
+a	O
+role	O
+for	O
+this	O
+protein	O
+in	O
+radiation	O
+-	O
+induced	O
+cell	O
+death	O
+.	O
+
+Thus	O
+,	O
+the	O
+B	O
+-	O
+S	O
+mutant	O
+does	O
+not	O
+mimic	O
+efficiently	O
+the	O
+chloroplastic	B-GENE
+GAPDHs	I-GENE
+,	O
+and	O
+long	O
+-	O
+range	O
+and	O
+/	O
+or	O
+second	O
+-	O
+layer	O
+effects	O
+,	O
+not	O
+easily	O
+predictable	O
+from	O
+visual	O
+inspection	O
+of	O
+three	O
+-	O
+dimensional	O
+structures	O
+,	O
+need	O
+to	O
+be	O
+taken	O
+into	O
+account	O
+for	O
+designing	O
+a	O
+true	O
+"	O
+chloroplastic	O
+-	O
+like	O
+"	O
+mutant	O
+of	O
+cytosolic	B-GENE
+GAPDH	I-GENE
+.	O
+
+Computer	O
+software	O
+assisted	O
+ordering	O
+(	O
+CSAO	O
+)	O
+was	O
+developed	O
+to	O
+integrate	O
+PN	O
+Ca	O
+:	O
+P	O
+solubility	O
+with	O
+clinical	O
+data	O
+to	O
+improve	O
+parenteral	O
+Ca	O
+and	O
+P	O
+administration	O
+.	O
+
+A	O
+similar	O
+chimera	O
+was	O
+assembled	O
+from	O
+the	O
+two	O
+halves	O
+of	O
+the	O
+molecule	O
+expressed	O
+separately	O
+in	O
+different	O
+bacteria	O
+and	O
+refolded	O
+together	O
+.	O
+
+The	O
+conditions	O
+for	O
+obtaining	O
+titanium	O
+dioxide	O
+from	O
+the	O
+substrates	O
+titanium	O
+tetrachloride	O
+and	O
+oxygen	O
+and	O
+applying	O
+this	O
+to	O
+a	O
+surgical	O
+stainless	O
+steel	O
+of	O
+the	O
+type	O
+316L	O
+by	O
+the	O
+plasma	O
+assisted	O
+chemical	O
+vapour	O
+deposition	O
+method	O
+have	O
+been	O
+determined	O
+.	O
+
+All	O
+six	O
+genes	O
+were	O
+cloned	O
+and	O
+characterised	O
+.	O
+
+We	O
+analysed	O
+two	O
+regions	O
+involved	O
+in	O
+preS2	B-GENE
+/	O
+S	B-GENE
+gene	I-GENE
+transcription	O
+of	O
+the	O
+HBV	O
+adw	O
+subtype	O
+:	O
+the	O
+diverged	O
+TATA	O
+box	O
+and	O
+a	O
+putative	O
+initiator	O
+element	O
+.	O
+
+Indeed	O
+the	O
+predicted	O
+folding	O
+of	O
+the	O
+5	O
+'	O
+and	O
+3	O
+'	O
+-	O
+untranslated	O
+regions	O
+revealed	O
+patterns	O
+of	O
+stem	O
+and	O
+loop	O
+structures	O
+conserved	O
+for	O
+all	O
+tick	O
+-	O
+borne	O
+flaviviruses	O
+suggesting	O
+a	O
+purifying	O
+selection	O
+for	O
+preservation	O
+of	O
+essential	O
+RNA	O
+secondary	O
+structures	O
+which	O
+could	O
+be	O
+involved	O
+in	O
+translational	O
+control	O
+and	O
+replication	O
+.	O
+
+EGF	B-GENE
+acts	O
+primarily	O
+by	O
+means	O
+of	O
+transactivation	O
+domain	O
+AF	O
+-	O
+1	O
+,	O
+whereas	O
+cAMP	O
+acts	O
+via	O
+transactivation	O
+domain	O
+AF	O
+-	O
+2	O
+of	O
+the	O
+ER	B-GENE
+.	O
+
+To	O
+determine	O
+which	O
+region	O
+of	O
+SulA	B-GENE
+is	O
+essential	O
+for	O
+the	O
+inhibition	O
+of	O
+cell	O
+division	O
+,	O
+we	O
+constructed	O
+a	O
+series	O
+of	O
+N	O
+-	O
+terminal	O
+and	O
+C	O
+-	O
+terminal	O
+deletions	O
+of	O
+SulA	B-GENE
+and	O
+a	O
+series	O
+of	O
+alanine	O
+substitution	O
+mutants	O
+.	O
+
+We	O
+have	O
+inactivated	O
+Krox	B-GENE
+-	I-GENE
+20	I-GENE
+by	O
+homologous	O
+recombination	O
+in	O
+ES	O
+cells	O
+and	O
+demonstrated	O
+that	O
+the	O
+mutation	O
+leads	O
+to	O
+the	O
+deletion	O
+of	O
+r3	O
+and	O
+r5	O
+.	O
+
+Recently	O
+we	O
+have	O
+performed	O
+a	O
+detailed	O
+analysis	O
+of	O
+specific	O
+neuronal	O
+populations	O
+affected	O
+by	O
+the	O
+mutation	O
+which	O
+shed	O
+new	O
+light	O
+on	O
+the	O
+role	O
+of	O
+Krox	B-GENE
+-	I-GENE
+20	I-GENE
+in	O
+the	O
+segmentation	O
+and	O
+on	O
+the	O
+physiological	O
+consequences	O
+of	O
+its	O
+inactivation	O
+.	O
+
+Consistent	O
+with	O
+its	O
+role	O
+in	O
+p53	B-GENE
+ubiquitination	O
+,	O
+mE6	B-GENE
+-	I-GENE
+AP	I-GENE
+was	O
+found	O
+both	O
+in	O
+the	O
+nucleus	O
+and	O
+cytosol	O
+,	O
+while	O
+Nedd	B-GENE
+-	I-GENE
+4	I-GENE
+was	O
+found	O
+only	O
+in	O
+the	O
+cytosol	O
+.	O
+
+SPP	B-GENE
+also	O
+induced	O
+transient	O
+tyrosine	O
+phosphorylation	O
+of	O
+focal	B-GENE
+adhesion	I-GENE
+kinase	I-GENE
+(	O
+p125	B-GENE
+(	O
+FAK	B-GENE
+)	O
+)	O
+,	O
+a	O
+cytosolic	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+that	O
+localizes	O
+in	O
+focal	O
+adhesions	O
+,	O
+and	O
+of	O
+the	O
+cytoskeleton	B-GENE
+-	I-GENE
+associated	I-GENE
+protein	I-GENE
+paxillin	I-GENE
+.	O
+
+Evaluation	O
+of	O
+myocardial	O
+perfusion	O
+by	O
+99mTc	O
+-	O
+tetrofosmin	O
+SPECT	O
+before	O
+and	O
+after	O
+emergent	O
+percutaneous	O
+transluminal	O
+coronary	O
+angioplasty	O
+for	O
+acute	O
+myocardial	O
+infarction	O
+
+A	O
+neonatal	O
+alloimmune	O
+thrombocytopenia	O
+with	O
+an	O
+HPA	B-GENE
+-	I-GENE
+3a	I-GENE
+(	O
+Baka	O
+)	O
+incompatibility	O
+was	O
+confirmed	O
+.	O
+
+Most	O
+eukaryotic	O
+mRNAs	O
+are	O
+translated	O
+by	O
+a	O
+"	O
+scanning	O
+ribosome	O
+"	O
+mechanism	O
+.	O
+
+Comparison	O
+of	O
+Tc	O
+-	O
+99m	O
+sestamibi	O
+perfusion	O
+imaging	O
+and	O
+echocardiography	O
+using	O
+an	O
+arbutamine	O
+infusion	O
+for	O
+the	O
+detection	O
+of	O
+coronary	O
+artery	O
+disease	O
+.	O
+
+Five	O
+of	O
+these	O
+have	O
+ocular	O
+or	O
+oculocutaneous	O
+albinism	O
+.	O
+
+Comprising	O
+a	O
+126	O
+-	O
+nucleotide	O
+5	O
+'	O
+untranscribed	O
+genomic	O
+sequence	O
+and	O
+a	O
+466	O
+-	O
+nucleotide	O
+5	O
+'	O
+noncoding	O
+cDNA	O
+sequence	O
+,	O
+the	O
+592	O
+-	O
+nucleotide	O
+5	O
+'	O
+CpG	O
+island	O
+lacked	O
+TATA	O
+and	O
+CAAT	O
+boxes	O
+but	O
+displayed	O
+a	O
+high	O
+G	O
++	O
+C	O
+content	O
+,	O
+was	O
+enriched	O
+for	O
+CpG	O
+dinucleotides	O
+,	O
+and	O
+contained	O
+a	O
+potential	O
+Sp1	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+features	O
+compatible	O
+with	O
+a	O
+housekeeping	O
+gene	O
+.	O
+
+SSeCKS	B-GENE
+(	O
+pronounced	O
+essex	O
+)	O
+encodes	O
+a	O
+major	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+substrate	O
+,	O
+the	O
+expression	O
+of	O
+which	O
+is	O
+down	O
+-	O
+regulated	O
+in	O
+src	B-GENE
+-	O
+and	O
+ras	B-GENE
+-	O
+transformed	O
+rodent	O
+fibroblasts	O
+but	O
+not	O
+in	O
+raf	O
+-	O
+transformed	O
+rodent	O
+fibroblasts	O
+(	O
+X	O
+.	O
+
+The	O
+1	O
+.	O
+1	O
+-	O
+and	O
+1	O
+.	O
+3	O
+-	O
+kb	O
+mRNA	O
+species	O
+were	O
+found	O
+only	O
+in	O
+the	O
+heart	O
+,	O
+and	O
+the	O
+2	O
+.	O
+6	O
+-	O
+kb	O
+species	O
+was	O
+found	O
+in	O
+the	O
+heart	O
+,	O
+kidney	O
+and	O
+brain	O
+,	O
+but	O
+not	O
+in	O
+skeletal	O
+muscle	O
+or	O
+liver	O
+.	O
+
+Taurine	O
+deficiency	O
+significantly	O
+depressed	O
+the	O
+amplitude	O
+of	O
+OP1	O
+and	O
+OP4	O
+.	O
+
+We	O
+have	O
+found	O
+that	O
+mcs4	B-GENE
+-	O
+cells	O
+are	O
+defective	O
+at	O
+activation	O
+of	O
+Spc1	B-GENE
+in	O
+response	O
+to	O
+various	O
+forms	O
+of	O
+stress	O
+.	O
+
+The	O
+extended	O
+rat	B-GENE
+SP	I-GENE
+-	I-GENE
+A	I-GENE
+isoforms	I-GENE
+were	O
+enriched	O
+in	O
+the	O
+more	O
+fully	O
+glycosylated	O
+and	O
+multimeric	O
+SP	B-GENE
+-	I-GENE
+A	I-GENE
+species	O
+separated	O
+on	O
+SDS	O
+-	O
+PAGE	O
+gels	O
+.	O
+
+Alternative	O
+splicing	O
+of	O
+CDC25B	B-GENE
+may	O
+therefore	O
+contribute	O
+to	O
+the	O
+control	O
+of	O
+cell	O
+proliferation	O
+.	O
+
+This	O
+investigation	O
+was	O
+undertaken	O
+to	O
+determine	O
+whether	O
+consuming	O
+several	O
+small	O
+feedings	O
+of	O
+preexercise	O
+carbohydrate	O
+(	O
+CHO	O
+)	O
+,	O
+rather	O
+than	O
+a	O
+single	O
+bolus	O
+,	O
+would	O
+affect	O
+blood	O
+glucose	O
+and	O
+insulin	B-GENE
+responses	O
+during	O
+rest	O
+and	O
+exercise	O
+.	O
+
+The	O
+findings	O
+suggest	O
+that	O
+ERP	O
+effects	O
+of	O
+distinct	O
+memory	O
+processes	O
+are	O
+differentially	O
+influenced	O
+by	O
+the	O
+encoding	O
+instructions	O
+.	O
+
+This	O
+coat	B-GENE
+protein	I-GENE
+consists	O
+of	O
+Sar1p	B-GENE
+,	O
+the	O
+Sec23p	B-GENE
+protein	I-GENE
+complex	I-GENE
+containing	O
+Sec23p	B-GENE
+and	O
+Sec24p	B-GENE
+,	O
+and	O
+the	O
+Sec13p	B-GENE
+protein	I-GENE
+complex	I-GENE
+containing	O
+Sec13p	B-GENE
+and	O
+a	O
+novel	O
+150	B-GENE
+-	I-GENE
+kDa	I-GENE
+protein	I-GENE
+,	I-GENE
+p150	I-GENE
+.	O
+
+The	O
+second	O
+primary	O
+mutant	O
+contained	O
+a	O
+proline	O
+-	O
+to	O
+-	O
+leucine	O
+change	O
+at	O
+position	O
+243	O
+(	O
+P243L	O
+)	O
+.	O
+
+Induction	O
+of	O
+correctly	O
+spliced	O
+germline	O
+transcripts	O
+is	O
+necessary	O
+to	O
+target	O
+a	O
+switch	O
+region	O
+for	O
+recombination	O
+and	O
+switching	O
+.	O
+
+Thus	O
+,	O
+the	O
+PCE	B-GENE
+binds	O
+a	O
+Pbx	B-GENE
+dimer	I-GENE
+partner	I-GENE
+that	O
+behaves	O
+unlike	O
+Class	B-GENE
+I	I-GENE
+Hox	I-GENE
+proteins	I-GENE
+.	O
+
+Furthermore	O
+,	O
+the	O
+NH2	O
+-	O
+terminal	O
+portion	O
+of	O
+the	O
+homologue	O
+was	O
+not	O
+translocated	O
+into	O
+the	O
+outer	O
+membrane	O
+without	O
+its	O
+COOH	O
+-	O
+terminal	O
+part	O
+.	O
+
+Molecular	O
+cloning	O
+and	O
+characterization	O
+of	O
+a	O
+cDNA	O
+,	O
+CHEMR1	B-GENE
+,	O
+encoding	O
+a	O
+chemokine	O
+receptor	O
+with	O
+a	O
+homology	O
+to	O
+the	O
+human	B-GENE
+C	I-GENE
+-	I-GENE
+C	I-GENE
+chemokine	I-GENE
+receptor	I-GENE
+,	O
+CCR	B-GENE
+-	I-GENE
+4	I-GENE
+.	O
+
+Organization	O
+of	O
+the	O
+human	B-GENE
+LU	I-GENE
+gene	I-GENE
+and	O
+molecular	O
+basis	O
+of	O
+the	O
+Lu	B-GENE
+(	I-GENE
+a	I-GENE
+)	I-GENE
+/	O
+Lu	B-GENE
+(	I-GENE
+b	I-GENE
+)	I-GENE
+blood	O
+group	O
+polymorphism	O
+.	O
+
+Whereas	O
+the	O
+mutant	O
+enzymes	O
+terminate	O
+normally	O
+at	O
+the	O
+late	O
+terminator	O
+in	O
+T7	O
+DNA	O
+(	O
+T	O
+(	O
+phi	O
+)	O
+)	O
+and	O
+rrnB	B-GENE
+T2	O
+,	O
+they	O
+fail	O
+to	O
+terminate	O
+at	O
+one	O
+of	O
+the	O
+termination	O
+sites	O
+of	O
+rrnB	B-GENE
+T1	O
+,	O
+and	O
+also	O
+fail	O
+to	O
+recognize	O
+the	O
+PTH	B-GENE
+and	O
+CJ	O
+signals	O
+.	O
+
+Cytological	O
+data	O
+suggest	O
+that	O
+the	O
+transgenes	O
+associate	O
+with	O
+a	O
+nucleolus	O
+.	O
+
+Light	B-GENE
+regulatory	I-GENE
+unit	I-GENE
+1	I-GENE
+(	O
+LRU1	B-GENE
+)	O
+is	O
+necessary	O
+for	O
+and	O
+sufficient	O
+to	O
+mediate	O
+light	O
+-	O
+dependent	O
+activation	O
+of	O
+the	O
+chalcone	B-GENE
+synthase	I-GENE
+(	I-GENE
+CHS	I-GENE
+)	I-GENE
+minimal	I-GENE
+promoter	I-GENE
+in	O
+Petroselinum	O
+crispum	O
+.	O
+
+The	O
+active	O
+state	O
+is	O
+terminated	O
+by	O
+hydrolysis	O
+of	O
+bound	O
+GTP	O
+,	O
+producing	O
+inactive	O
+ARF	B-GENE
+-	I-GENE
+GDP	I-GENE
+.	O
+
+We	O
+suggest	O
+that	O
+apart	O
+from	O
+the	O
+World	O
+Summit	O
+for	O
+Children	O
+'	O
+s	O
+under	O
+-	O
+five	O
+mortality	O
+target	O
+for	O
+the	O
+year	O
+2000	O
+,	O
+intraregional	O
+targets	O
+to	O
+reduce	O
+geographical	O
+inequalities	O
+in	O
+under	O
+-	O
+five	O
+mortality	O
+should	O
+be	O
+specified	O
+.	O
+
+The	O
+immunophilin	B-GENE
+,	O
+which	O
+can	O
+be	O
+of	O
+the	O
+FK506	O
+-	O
+or	O
+cyclosporin	O
+A	O
+-	O
+binding	O
+class	O
+,	O
+binds	O
+to	O
+hsp90	B-GENE
+via	O
+its	O
+tetratricopeptide	O
+repeat	O
+(	O
+TPR	O
+)	O
+domain	O
+,	O
+and	O
+different	O
+receptor	O
+heterocomplexes	O
+exist	O
+depending	O
+upon	O
+which	O
+immunophilin	B-GENE
+occupies	O
+the	O
+TPR	O
+-	O
+binding	O
+region	O
+of	O
+hsp90	B-GENE
+.	O
+
+Sequencing	O
+of	O
+the	O
+facB	B-GENE
+gene	I-GENE
+revealed	O
+that	O
+it	O
+encodes	O
+a	O
+protein	O
+that	O
+contains	O
+an	O
+N	O
+-	O
+terminal	O
+GAL4	B-GENE
+-	O
+like	O
+Zn	O
+(	O
+II	O
+)	O
+2Cys6	O
+(	O
+or	O
+C6	O
+zinc	O
+)	O
+binuclear	O
+cluster	O
+for	O
+DNA	O
+binding	O
+,	O
+leucine	O
+zipper	O
+-	O
+like	O
+heptad	O
+repeat	O
+motifs	O
+and	O
+central	O
+and	O
+C	O
+-	O
+terminal	O
+acidic	O
+alpha	O
+-	O
+helical	O
+regions	O
+,	O
+consistent	O
+with	O
+a	O
+function	O
+as	O
+a	O
+DNA	O
+-	O
+binding	O
+transcriptional	O
+activator	O
+.	O
+
+Overexpression	O
+of	O
+Sed5p	B-GENE
+allowed	O
+growth	O
+in	O
+the	O
+absence	O
+of	O
+Vti1p	B-GENE
+.	O
+
+The	O
+coding	O
+region	O
+of	O
+mkh1	B-GENE
+is	O
+contained	O
+within	O
+a	O
+single	O
+exon	O
+encoding	O
+a	O
+1	O
+,	O
+116	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+.	O
+
+Strikingly	O
+,	O
+stoichiometric	O
+association	O
+of	O
+p107	B-GENE
+or	O
+p130	B-GENE
+with	O
+either	O
+cyclin	B-GENE
+E	I-GENE
+-	O
+cdk2	B-GENE
+or	O
+cyclin	B-GENE
+A	I-GENE
+-	O
+cdk2	B-GENE
+negated	O
+the	O
+activities	O
+of	O
+these	O
+kinases	O
+.	O
+
+Furthermore	O
+,	O
+p150	B-GENE
+suppresses	O
+actin	B-GENE
+gelation	O
+,	O
+which	O
+is	O
+induced	O
+by	O
+smooth	B-GENE
+muscle	I-GENE
+alpha	I-GENE
+-	I-GENE
+actinin	I-GENE
+.	O
+
+Denaturation	O
+of	O
+the	O
+simian	O
+virus	O
+40	O
+origin	O
+of	O
+replication	O
+mediated	O
+by	O
+human	B-GENE
+replication	I-GENE
+protein	I-GENE
+A	I-GENE
+.	O
+
+This	O
+effect	O
+was	O
+abolished	O
+once	O
+the	O
+EM	O
+motif	O
+in	O
+the	O
+promoter	O
+-	O
+reporter	O
+construct	O
+was	O
+mutated	O
+,	O
+thus	O
+suggesting	O
+that	O
+the	O
+synergistic	O
+transactivation	O
+function	O
+of	O
+the	O
+TEF	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+Max	B-GENE
+heterotypic	O
+complex	O
+is	O
+mediated	O
+through	O
+binding	O
+of	O
+the	O
+complex	O
+to	O
+the	O
+EM	O
+motif	O
+.	O
+
+Interdigitated	O
+residues	O
+within	O
+a	O
+small	O
+region	O
+of	O
+VP16	B-GENE
+interact	O
+with	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+HCF	B-GENE
+,	O
+and	O
+DNA	O
+.	O
+
+With	O
+a	O
+view	O
+to	O
+identifying	O
+other	O
+important	O
+U14	B-GENE
+interactions	O
+,	O
+a	O
+stem	O
+-	O
+loop	O
+domain	O
+required	O
+for	O
+activity	O
+of	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+U14	I-GENE
+RNAs	I-GENE
+(	O
+the	O
+Y	O
+domain	O
+)	O
+was	O
+first	O
+subjected	O
+to	O
+detailed	O
+mutational	O
+analysis	O
+.	O
+
+Based	O
+on	O
+these	O
+results	O
+and	O
+because	O
+Cdc68	B-GENE
+has	O
+been	O
+implicated	O
+as	O
+a	O
+regulator	O
+of	O
+chromatin	O
+structure	O
+,	O
+we	O
+postulate	O
+that	O
+polymerase	B-GENE
+alpha	I-GENE
+may	O
+interact	O
+with	O
+these	O
+proteins	O
+to	O
+gain	O
+access	O
+to	O
+its	O
+template	O
+or	O
+to	O
+origins	O
+of	O
+replication	O
+in	O
+vivo	O
+.	O
+
+Even	O
+when	O
+the	O
+inoculum	O
+size	O
+was	O
+reduced	O
+sixfold	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+6	O
+x	O
+10	O
+(	O
+6	O
+)	O
+CFU	O
+/	O
+mouse	O
+)	O
+,	O
+50	O
+%	O
+of	O
+the	O
+RB6	B-GENE
+-	I-GENE
+8C5	I-GENE
+-	O
+treated	O
+animals	O
+died	O
+within	O
+6	O
+days	O
+.	O
+
+In	O
+12	O
+cases	O
+(	O
+3	O
+.	O
+1	O
+%	O
+)	O
+,	O
+a	O
+change	O
+in	O
+stage	O
+resulted	O
+.	O
+
+Promoter	O
+recognition	O
+algorithms	O
+identified	O
+divergent	O
+promoter	O
+elements	O
+within	O
+the	O
+CpG	O
+island	O
+,	O
+which	O
+lies	O
+between	O
+the	O
+ATM	B-GENE
+and	O
+E14	B-GENE
+/	O
+NPAT	B-GENE
+genes	O
+,	O
+and	O
+provide	O
+evidence	O
+for	O
+a	O
+putative	O
+second	O
+ATM	B-GENE
+promoter	I-GENE
+located	O
+within	O
+intron	O
+3	O
+,	O
+immediately	O
+upstream	O
+of	O
+the	O
+first	O
+coding	O
+exon	O
+.	O
+
+Recombinant	B-GENE
+soluble	I-GENE
+pMCP	I-GENE
+that	O
+lacked	O
+transmembrane	O
+and	O
+cytoplasmic	O
+domains	O
+had	O
+factor	B-GENE
+I	I-GENE
+cofactor	I-GENE
+activity	O
+in	O
+C3b	B-GENE
+cleavage	O
+,	O
+indicating	O
+that	O
+it	O
+is	O
+functionally	O
+,	O
+as	O
+well	O
+as	O
+structurally	O
+homologous	O
+to	O
+MCP	B-GENE
+.	O
+
+Clinical	O
+and	O
+haematological	O
+signs	O
+are	O
+not	O
+specific	O
+in	O
+this	O
+setting	O
+,	O
+and	O
+the	O
+diagnosis	O
+relies	O
+on	O
+histological	O
+features	O
+,	O
+mainly	O
+bone	O
+marrow	O
+examination	O
+.	O
+
+Spatial	O
+zones	O
+for	O
+muscle	O
+coactivation	O
+and	O
+the	O
+control	O
+of	O
+postural	O
+stability	O
+.	O
+
+Liquid	O
+chromatographic	O
+separation	O
+was	O
+achieved	O
+on	O
+a	O
+Zorbax	O
+RX	O
+C8	O
+analytical	O
+column	O
+using	O
+gradient	O
+elution	O
+.	O
+
+The	O
+linear	O
+plasmid	O
+pDHL1	O
+from	O
+Debaryomyces	O
+hansenii	O
+encodes	O
+a	O
+protein	O
+highly	O
+homologous	O
+to	O
+the	O
+pGKL1	B-GENE
+-	I-GENE
+plasmid	I-GENE
+DNA	I-GENE
+polymerase	I-GENE
+.	O
+
+The	O
+p20	B-GENE
+-	I-GENE
+CGGBP	I-GENE
+gene	I-GENE
+is	O
+conserved	O
+among	O
+mammals	O
+but	O
+shows	O
+no	O
+homology	O
+to	O
+non	O
+-	O
+vertebrate	O
+species	O
+.	O
+
+The	O
+data	O
+suggest	O
+that	O
+like	O
+in	O
+yeast	O
+,	O
+in	O
+plants	O
+a	O
+certain	O
+subfamily	O
+of	O
+UBC	B-GENE
+is	O
+specifically	O
+involved	O
+in	O
+the	O
+proteolytic	O
+degradation	O
+of	O
+abnormal	O
+proteins	O
+as	O
+result	O
+of	O
+stress	O
+.	O
+
+The	O
+pWP	B-GENE
+-	I-GENE
+19	I-GENE
+also	O
+encodes	O
+the	O
+AAV	O
+inverted	O
+terminal	O
+repeats	O
+for	O
+integration	O
+and	O
+replication	O
+and	O
+the	O
+herpes	O
+virus	O
+thymidine	B-GENE
+kinase	I-GENE
+promoter	O
+-	O
+driven	O
+gene	O
+for	O
+neomycin	O
+resistance	O
+(	O
+neoR	B-GENE
+)	O
+.	O
+
+We	O
+have	O
+developed	O
+a	O
+rAAV	O
+-	O
+mediated	O
+gene	O
+transfer	O
+system	O
+for	O
+the	O
+rat	B-GENE
+preproinsulin	I-GENE
+II	I-GENE
+gene	I-GENE
+.	O
+
+A	O
+striking	O
+feature	O
+of	O
+the	O
+recombinant	B-GENE
+H19	I-GENE
+allele	I-GENE
+is	O
+the	O
+occurrence	O
+of	O
+a	O
+parental	O
+imprint	O
+set	O
+on	O
+the	O
+neo	B-GENE
+replacement	I-GENE
+cassette	I-GENE
+.	O
+
+This	O
+indicates	O
+that	O
+recruitment	O
+of	O
+large	B-GENE
+T	I-GENE
+antigen	I-GENE
+to	O
+the	O
+rRNA	O
+promoter	O
+by	O
+SL1	B-GENE
+constitutes	O
+a	O
+crucial	O
+step	O
+in	O
+the	O
+activation	O
+process	O
+.	O
+
+In	O
+1990	O
+,	O
+an	O
+International	O
+Commission	O
+for	O
+the	O
+Certification	O
+of	O
+Eradication	O
+of	O
+Poliomyelitis	O
+Eradication	O
+(	O
+ICCPE	O
+)	O
+was	O
+established	O
+by	O
+the	O
+Pan	O
+American	O
+Health	O
+Organization	O
+to	O
+eventually	O
+determine	O
+if	O
+transmission	O
+was	O
+interrupted	O
+.	O
+
+Functional	O
+and	O
+regulatory	O
+analysis	O
+of	O
+the	O
+two	O
+copies	O
+of	O
+the	O
+fixNOQP	B-GENE
+operon	I-GENE
+of	O
+Rhizobium	O
+leguminosarum	O
+strain	O
+VF39	O
+.	O
+
+This	O
+study	O
+describes	O
+a	O
+new	O
+MADS	B-GENE
+box	I-GENE
+gene	I-GENE
+,	O
+nmhC5	B-GENE
+,	O
+which	O
+along	O
+with	O
+nmh7	B-GENE
+(	O
+J	O
+.	O
+
+Lung	O
+and	O
+multi	O
+-	O
+system	O
+damage	O
+were	O
+early	O
+indicators	O
+of	O
+poor	O
+outcome	O
+in	O
+severe	O
+non	O
+-	O
+fatal	O
+disease	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+the	O
+bulbospinal	O
+micturition	O
+reflex	O
+evoked	O
+by	O
+bladder	O
+filling	O
+and	O
+L	O
+-	O
+dopa	O
+involves	O
+a	O
+descending	O
+pathway	O
+where	O
+transmission	O
+is	O
+partly	O
+mediated	O
+by	O
+spinal	B-GENE
+alpha	I-GENE
+1	I-GENE
+-	I-GENE
+adrenoceptors	I-GENE
+.	O
+
+Disturbance	O
+of	O
+regeneration	O
+in	O
+the	O
+above	O
+pathological	O
+condition	O
+results	O
+from	O
+the	O
+damage	O
+to	O
+tunica	O
+propria	O
+and	O
+loss	O
+of	O
+its	O
+function	O
+for	O
+the	O
+support	O
+of	O
+structural	O
+homeostasis	O
+.	O
+
+Sternocleidomastoid	O
+,	O
+neck	O
+or	O
+facial	O
+muscles	O
+wasting	O
+were	O
+also	O
+found	O
+in	O
+three	O
+cases	O
+.	O
+
+Identification	O
+of	O
+five	O
+new	O
+genes	O
+,	O
+closely	O
+related	O
+to	O
+the	O
+interleukin	B-GENE
+-	I-GENE
+1beta	I-GENE
+converting	I-GENE
+enzyme	I-GENE
+gene	I-GENE
+,	O
+that	O
+do	O
+not	O
+encode	O
+functional	O
+proteases	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+mature	O
+region	O
+is	O
+highly	O
+conserved	O
+in	O
+other	O
+serine	B-GENE
+carboxypeptidases	I-GENE
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+AML1a	B-GENE
+,	O
+which	O
+solely	O
+has	O
+no	O
+effects	O
+as	O
+a	O
+transcriptional	O
+regulator	O
+,	O
+dominantly	O
+suppresses	O
+transcriptional	O
+activation	O
+by	O
+AML1b	B-GENE
+,	O
+and	O
+that	O
+AML1a	B-GENE
+exhibits	O
+the	O
+higher	O
+affinity	O
+for	O
+DNA	O
+-	O
+binding	O
+than	O
+AML1b	B-GENE
+.	O
+
+However	O
+,	O
+using	O
+ATL	O
+-	O
+16T	O
+nuclear	O
+extract	O
+,	O
+we	O
+demonstrated	O
+that	O
+GATA	B-GENE
+-	I-GENE
+4	I-GENE
+is	O
+the	O
+only	O
+GATA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+that	O
+forms	O
+specific	O
+DNA	O
+-	O
+protein	O
+complex	O
+with	O
+the	O
+-	O
+70	O
+GATA	O
+site	O
+.	O
+
+The	O
+impact	O
+of	O
+social	O
+support	O
+on	O
+the	O
+relationships	O
+of	O
+gay	O
+male	O
+couples	O
+is	O
+examined	O
+.	O
+
+The	O
+ubiquitously	O
+expressed	O
+hypoxia	B-GENE
+-	I-GENE
+inducible	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+HIF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+is	O
+involved	O
+in	O
+expression	O
+of	O
+a	O
+large	O
+number	O
+of	O
+oxygen	O
+-	O
+regulated	O
+genes	O
+.	O
+
+Stromelysin	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+matrix	B-GENE
+metalloproteinase	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+MMP	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+,	O
+is	O
+an	O
+important	O
+endopeptidase	O
+selectively	O
+expressed	O
+by	O
+somatic	O
+cells	O
+in	O
+organ	O
+tissues	O
+.	O
+
+Tendon	O
+also	O
+shows	O
+a	O
+degree	O
+of	O
+extensibility	O
+.	O
+
+Surveillance	O
+for	O
+preeclampsia	O
+was	O
+conducted	O
+by	O
+personnel	O
+unaware	O
+of	O
+treatment	O
+-	O
+group	O
+assignments	O
+,	O
+using	O
+standardized	O
+measurements	O
+of	O
+blood	O
+pressure	O
+and	O
+urinary	O
+protein	O
+excretion	O
+at	O
+uniformly	O
+scheduled	O
+prenatal	O
+visits	O
+,	O
+protocols	O
+for	O
+monitoring	O
+these	O
+measurements	O
+during	O
+the	O
+hospitalization	O
+for	O
+delivery	O
+,	O
+and	O
+reviews	O
+of	O
+medical	O
+records	O
+of	O
+unscheduled	O
+outpatient	O
+visits	O
+and	O
+all	O
+hospitalizations	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprint	O
+analysis	O
+identified	O
+a	O
+protected	O
+region	O
+from	O
+-	O
+37	O
+to	O
+-	O
+53	O
+.	O
+
+We	O
+isolated	O
+several	O
+overlapping	O
+A	O
+-	O
+phage	O
+and	O
+cosmid	O
+clones	O
+that	O
+cover	O
+more	O
+than	O
+100	O
+kb	O
+of	O
+human	O
+DNA	O
+and	O
+contained	O
+the	O
+entire	O
+VDR	B-GENE
+gene	I-GENE
+.	O
+
+Here	O
+,	O
+we	O
+correlate	O
+Dox	O
+effects	O
+on	O
+cell	O
+cycle	O
+with	O
+changes	O
+of	O
+E2F	B-GENE
+/	O
+DP	B-GENE
+complexes	O
+and	O
+activity	O
+in	O
+differentiating	O
+C2C12	O
+myocytes	O
+.	O
+
+The	O
+products	O
+of	O
+the	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+CIN1	I-GENE
+,	O
+CIN2	B-GENE
+and	O
+CIN4	B-GENE
+genes	I-GENE
+participate	O
+in	O
+a	O
+nonessential	O
+pathway	O
+required	O
+for	O
+normal	O
+microtubule	O
+function	O
+.	O
+
+Vitrectomy	O
+was	O
+still	O
+a	O
+significant	O
+risk	O
+factor	O
+when	O
+macular	O
+holes	O
+were	O
+excluded	O
+.	O
+
+Invited	O
+editorial	O
+on	O
+"	O
+Acute	O
+and	O
+chronic	O
+effects	O
+of	O
+exercise	O
+on	O
+leptin	B-GENE
+levels	O
+in	O
+humans	O
+"	O
+.	O
+
+Both	O
+promoters	O
+lack	O
+a	O
+TATA	O
+box	O
+,	O
+and	O
+Pint	B-GENE
+belongs	O
+to	O
+the	O
+MED	B-GENE
+-	I-GENE
+1	I-GENE
+class	O
+of	O
+promoters	O
+,	O
+which	O
+initiate	O
+transcription	O
+at	O
+multiple	O
+sites	O
+.	O
+
+Serum	B-GENE
+response	I-GENE
+factor	I-GENE
+(	O
+SRF	B-GENE
+)	O
+,	O
+a	O
+member	O
+of	O
+an	O
+ancient	O
+family	O
+of	O
+DNA	O
+-	O
+binding	O
+proteins	O
+,	O
+is	O
+generally	O
+assumed	O
+to	O
+be	O
+a	O
+ubiquitous	O
+transcription	O
+factor	O
+involved	O
+in	O
+regulating	O
+growth	O
+factor	O
+-	O
+responsive	O
+genes	O
+.	O
+
+We	O
+have	O
+initiated	O
+studies	O
+to	O
+identify	O
+candidate	O
+signal	O
+transducers	O
+that	O
+associate	O
+with	O
+the	O
+cytosolic	O
+domain	O
+(	O
+cd	O
+)	O
+of	O
+the	O
+IL	B-GENE
+-	I-GENE
+1R	I-GENE
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+sought	O
+to	O
+identify	O
+mechanisms	O
+that	O
+could	O
+account	O
+for	O
+the	O
+antimitogenic	O
+effects	O
+of	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+.	O
+
+Pseudomonas	O
+aeruginosa	O
+strains	O
+infecting	O
+patients	O
+with	O
+cystic	O
+fibrosis	O
+(	O
+CF	O
+)	O
+acquire	O
+a	O
+mucoid	O
+phenotype	O
+due	O
+to	O
+overproduction	O
+of	O
+alginate	O
+.	O
+
+Activity	O
+of	O
+palgD	B-GENE
+in	O
+the	O
+cysB	B-GENE
+mutant	I-GENE
+,	O
+in	O
+CHA	O
+and	O
+in	O
+the	O
+non	O
+-	O
+mucoid	O
+strain	O
+PAO	O
+was	O
+assessed	O
+by	O
+the	O
+use	O
+of	O
+a	O
+transcriptional	O
+algD	B-GENE
+-	O
+xylE	B-GENE
+fusion	O
+.	O
+
+The	O
+Man9	B-GENE
+-	I-GENE
+mannosidase	I-GENE
+specificity	O
+of	O
+the	O
+cDNA	O
+construct	O
+was	O
+verified	O
+by	O
+the	O
+observation	O
+that	O
+all	O
+peptide	O
+sequences	O
+derived	O
+from	O
+a	O
+previously	O
+purified	O
+,	O
+catalytically	O
+active	O
+49	O
+-	O
+kDa	O
+fragment	O
+were	O
+found	O
+within	O
+the	O
+coding	O
+region	O
+.	O
+
+A	O
+soluble	O
+62	O
+-	O
+kDa	O
+protein	O
+was	O
+produced	O
+without	O
+the	O
+proteolytic	O
+processing	O
+by	O
+inserting	O
+the	O
+coding	O
+sequence	O
+of	O
+amino	O
+acids	O
+112	O
+to	O
+660	O
+of	O
+ORF	O
+-	O
+2	O
+in	O
+a	O
+baculovirus	O
+expression	O
+vector	O
+and	O
+using	O
+the	O
+corresponding	O
+virus	O
+to	O
+infect	O
+Sf9	O
+cells	O
+.	O
+
+The	O
+CPK	B-GENE
+-	I-GENE
+MB	I-GENE
+isoenzyme	O
+showed	O
+no	O
+percentage	O
+increase	O
+of	O
+total	O
+CPK	B-GENE
+higher	O
+than	O
+5	O
+%	O
+,	O
+measured	O
+at	O
+6	O
+,	O
+12	O
+,	O
+and	O
+24	O
+h	O
+after	O
+the	O
+shock	O
+,	O
+independent	O
+of	O
+the	O
+number	O
+of	O
+attempts	O
+of	O
+cardioversion	O
+.	O
+
+Serum	O
+and	O
+peritoneal	O
+dialysis	O
+fluid	O
+(	O
+PDF	O
+)	O
+were	O
+collected	O
+for	O
+assay	O
+throughout	O
+the	O
+course	O
+of	O
+the	O
+study	O
+and	O
+for	O
+5	O
+days	O
+thereafter	O
+.	O
+
+Results	O
+support	O
+the	O
+hypothesis	O
+that	O
+endogenous	B-GENE
+corticotropin	I-GENE
+-	I-GENE
+releasing	I-GENE
+factor	I-GENE
+,	O
+perhaps	O
+acting	O
+at	O
+a	O
+peripheral	O
+binding	O
+site	O
+,	O
+suppresses	O
+the	O
+active	O
+behavioral	O
+response	O
+characteristic	O
+of	O
+pups	O
+during	O
+the	O
+early	O
+phase	O
+of	O
+isolation	O
+in	O
+novel	O
+surroundings	O
+.	O
+
+Liver	O
+regional	O
+blood	O
+volume	O
+(	O
+LRBV	O
+)	O
+is	O
+altered	O
+by	O
+several	O
+disease	O
+states	O
+and	O
+various	O
+drugs	O
+.	O
+
+The	O
+gray	O
+matter	O
+NAA	O
+/	O
+mI	O
+ratio	O
+clearly	O
+separated	O
+the	O
+two	O
+groups	O
+.	O
+
+As	O
+with	O
+the	O
+murine	B-GENE
+and	I-GENE
+human	I-GENE
+mb	I-GENE
+-	I-GENE
+1	I-GENE
+genes	I-GENE
+,	O
+the	O
+5	O
+'	O
+region	O
+of	O
+the	O
+bovine	B-GENE
+mb	I-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+lacked	O
+a	O
+TATA	O
+box	O
+.	O
+
+Chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+assays	O
+examining	O
+the	O
+ability	O
+of	O
+IE86	B-GENE
+to	O
+repress	O
+activity	O
+from	O
+the	O
+HCMV	O
+major	O
+IE	B-GENE
+promoter	I-GENE
+or	O
+activate	O
+the	O
+HCMV	B-GENE
+early	I-GENE
+promoter	I-GENE
+for	O
+the	O
+2	O
+.	O
+2	O
+-	O
+kb	O
+class	O
+of	O
+RNAs	O
+demonstrated	O
+the	O
+functional	O
+integrity	O
+of	O
+the	O
+IE86	B-GENE
+protein	I-GENE
+.	O
+
+ORF	O
+M1	O
+has	O
+striking	O
+homology	O
+to	O
+poxvirus	O
+serpins	B-GENE
+,	O
+while	O
+ORF	O
+M11	O
+encodes	O
+a	O
+potential	O
+homolog	O
+of	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+like	I-GENE
+molecules	I-GENE
+encoded	O
+by	O
+other	O
+gammaherpesviruses	O
+(	O
+gene	B-GENE
+16	I-GENE
+of	O
+HVS	O
+and	O
+KSHV	O
+and	O
+the	O
+BHRF1	B-GENE
+gene	I-GENE
+of	O
+EBV	O
+)	O
+.	O
+
+Transcription	O
+factor	O
+binding	O
+sites	O
+downstream	O
+of	O
+the	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+transcription	O
+start	O
+site	O
+are	O
+important	O
+for	O
+virus	O
+infectivity	O
+.	O
+
+Crystal	O
+structure	O
+of	O
+an	O
+oligomer	O
+of	O
+proteolytic	O
+zymogens	O
+:	O
+detailed	O
+conformational	O
+analysis	O
+of	O
+the	O
+bovine	O
+ternary	O
+complex	O
+and	O
+implications	O
+for	O
+their	O
+activation	O
+.	O
+
+Through	O
+transient	O
+transfection	O
+of	O
+NIH3T3	O
+fibroblast	O
+cells	O
+and	O
+gel	O
+mobility	O
+shift	O
+assays	O
+,	O
+the	O
+functional	O
+binding	O
+site	O
+was	O
+localized	O
+to	O
+a	O
+short	O
+region	O
+(	O
+-	O
+318	O
+to	O
+-	O
+303	O
+bp	O
+from	O
+the	O
+transcription	O
+start	O
+site	O
+)	O
+which	O
+has	O
+a	O
+CTCCC	O
+sequence	O
+.	O
+
+We	O
+suppose	O
+that	O
+this	O
+injection	O
+speed	O
+(	O
+0	O
+.	O
+1	O
+-	O
+0	O
+.	O
+2	O
+ml	O
+.	O
+s	O
+-	O
+1	O
+)	O
+is	O
+suitable	O
+for	O
+spinal	O
+anesthesia	O
+.	O
+
+The	O
+current	O
+study	O
+demonstrates	O
+that	O
+T3	O
+-	O
+activated	O
+transcription	O
+of	O
+the	O
+NADPH	B-GENE
+:	I-GENE
+cytochrome	I-GENE
+P450	I-GENE
+oxidoreductase	I-GENE
+(	O
+P450R	B-GENE
+)	O
+gene	O
+is	O
+dependent	O
+on	O
+the	O
+thyroid	O
+hormonal	O
+status	O
+of	O
+the	O
+animal	O
+,	O
+with	O
+both	O
+transcriptional	O
+and	O
+post	O
+-	O
+transcriptional	O
+pathways	O
+being	O
+important	O
+in	O
+regulating	O
+the	O
+cellular	O
+P450R	B-GENE
+mRNA	O
+level	O
+.	O
+
+The	O
+behavior	O
+of	O
+different	O
+types	O
+of	O
+polytetrafluoroethylene	O
+(	O
+PTFE	O
+)	O
+prostheses	O
+in	O
+the	O
+reparative	O
+scarring	O
+process	O
+of	O
+abdominal	O
+wall	O
+defects	O
+.	O
+
+The	O
+control	O
+group	O
+revealed	O
+significantly	O
+higher	O
+levels	O
+of	O
+coagulation	B-GENE
+factors	I-GENE
+II	I-GENE
+,	I-GENE
+V	I-GENE
+and	I-GENE
+VIII	I-GENE
+,	O
+compared	O
+to	O
+the	O
+index	O
+group	O
+.	O
+
+Stereotactic	O
+radiofrequency	O
+lesioning	O
+of	O
+the	O
+hamartoma	O
+resulted	O
+in	O
+seizure	O
+remission	O
+without	O
+complications	O
+20	O
+months	O
+after	O
+surgery	O
+.	O
+
+If	O
+E	O
+.	O
+coli	O
+is	O
+present	O
+in	O
+any	O
+source	O
+water	O
+sample	O
+,	O
+the	O
+borehole	O
+and	O
+any	O
+directly	O
+connected	O
+borehole	O
+should	O
+be	O
+embargoed	O
+.	O
+
+The	O
+following	O
+technique	O
+describes	O
+a	O
+modification	O
+to	O
+a	O
+bar	O
+superstructure	O
+that	O
+provided	O
+the	O
+advantages	O
+of	O
+convenience	O
+,	O
+security	O
+,	O
+and	O
+consistent	O
+positioning	O
+even	O
+though	O
+one	O
+implant	O
+was	O
+lost	O
+and	O
+the	O
+angulation	O
+of	O
+implants	O
+limited	O
+accuracy	O
+.	O
+
+In	O
+summary	O
+,	O
+DDC	O
+express	O
+receptors	O
+for	O
+a	O
+broad	O
+panel	O
+of	O
+cytokines	O
+,	O
+even	O
+receptors	O
+for	O
+cytokines	O
+whose	O
+effects	O
+on	O
+DC	O
+are	O
+still	O
+unknown	O
+(	O
+i	O
+.	O
+e	O
+.	O
+
+Its	O
+potential	O
+as	O
+a	O
+diagnostic	O
+tool	O
+for	O
+epidemiological	O
+surveillance	O
+was	O
+assessed	O
+in	O
+comparison	O
+with	O
+three	O
+other	O
+diagnostic	O
+tests	O
+:	O
+stool	O
+examination	O
+,	O
+ELISA	O
+with	O
+soluble	B-GENE
+egg	I-GENE
+antigen	I-GENE
+(	O
+SEA	B-GENE
+)	O
+and	O
+the	O
+circumoval	O
+precipitin	B-GENE
+test	O
+(	O
+COPT	O
+)	O
+.	O
+
+These	O
+analyses	O
+demonstrate	O
+that	O
+the	O
+dUTPase	B-GENE
+isoforms	O
+are	O
+encoded	O
+by	O
+the	O
+same	O
+gene	O
+with	O
+isoform	O
+-	O
+specific	O
+transcripts	O
+arising	O
+through	O
+the	O
+use	O
+of	O
+alternative	O
+5	O
+'	O
+exons	O
+.	O
+
+The	O
+selective	O
+5	B-GENE
+-	I-GENE
+HT3	I-GENE
+receptor	I-GENE
+antagonists	O
+ramosetron	O
+(	O
+YM060	O
+)	O
+,	O
+YM114	O
+(	O
+KAE	O
+-	O
+393	O
+)	O
+,	O
+granisetron	O
+and	O
+ondansetron	O
+,	O
+and	O
+the	O
+substituted	O
+benzamides	O
+(	O
+5	B-GENE
+-	I-GENE
+HT4	I-GENE
+receptor	I-GENE
+agonist	O
+/	O
+5	B-GENE
+-	I-GENE
+HT3	I-GENE
+receptor	I-GENE
+antagonists	O
+)	O
+cisapride	O
+mosapride	O
+and	O
+SC	O
+-	O
+53116	O
+dose	O
+-	O
+dependently	O
+enhanced	O
+gastric	O
+emptying	O
+in	O
+normal	O
+rats	O
+.	O
+
+Re	O
+-	O
+evaluation	O
+of	O
+the	O
+biopsy	O
+specimen	O
+from	O
+the	O
+right	O
+hip	O
+taken	O
+at	O
+the	O
+time	O
+of	O
+the	O
+initial	O
+operation	O
+showed	O
+areas	O
+of	O
+chondrosarcoma	O
+arising	O
+in	O
+the	O
+background	O
+of	O
+synovial	O
+chondromatosis	O
+.	O
+
+All	O
+corneal	O
+buttons	O
+were	O
+processed	O
+for	O
+histopathologic	O
+and	O
+electron	O
+microscopic	O
+studies	O
+.	O
+
+3600	O
+-	O
+fold	O
+to	O
+apparent	O
+homogeneity	O
+with	O
+a	O
+41	O
+%	O
+yield	O
+by	O
+affinity	O
+chromatography	O
+utilizing	O
+DNA	O
+-	O
+cellulose	O
+;	O
+the	O
+purity	O
+of	O
+the	O
+final	O
+preparation	O
+was	O
+assessed	O
+by	O
+SDS	O
+/	O
+PAGE	O
+,	O
+lack	O
+of	O
+contamination	O
+by	O
+other	O
+nucleases	O
+and	O
+production	O
+of	O
+a	O
+monospecific	O
+antibody	O
+against	O
+the	O
+enzyme	O
+.	O
+
+Human	B-GENE
+thymine	I-GENE
+-	I-GENE
+DNA	I-GENE
+glycosylase	I-GENE
+maps	O
+at	O
+chromosome	O
+12q22	O
+-	O
+q24	O
+.	O
+1	O
+:	O
+a	O
+region	O
+of	O
+high	O
+loss	O
+of	O
+heterozygosity	O
+in	O
+gastric	O
+cancer	O
+.	O
+
+FOG	B-GENE
+is	O
+coexpressed	O
+with	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+during	O
+embryonic	O
+development	O
+and	O
+in	O
+erythroid	O
+and	O
+megakaryocytic	O
+cells	O
+.	O
+
+We	O
+further	O
+found	O
+that	O
+KmMig1p	B-GENE
+is	O
+fully	O
+functional	O
+when	O
+expressed	O
+in	O
+S	O
+.	O
+cerevisiae	O
+.	O
+
+Autoimmune	O
+neutropenia	O
+(	O
+AIN	O
+)	O
+is	O
+a	O
+frequent	O
+cause	O
+of	O
+chronic	O
+neutropenia	O
+especially	O
+in	O
+youngest	O
+children	O
+.	O
+
+With	O
+regard	O
+to	O
+the	O
+characteristic	O
+expression	O
+pattern	O
+of	O
+DJ	B-GENE
+protein	I-GENE
+and	O
+its	O
+conspicuous	O
+repeat	O
+units	O
+possible	O
+functional	O
+roles	O
+are	O
+discussed	O
+.	O
+
+Future	O
+analysis	O
+of	O
+long	O
+-	O
+term	O
+outcome	O
+measures	O
+of	O
+performance	O
+with	O
+the	O
+implant	O
+will	O
+confirm	O
+or	O
+dispute	O
+the	O
+benefit	O
+of	O
+ear	O
+selection	O
+using	O
+the	O
+Prom	O
+-	O
+EABR	O
+.	O
+
+This	O
+protein	O
+,	O
+designated	O
+p532	B-GENE
+based	O
+on	O
+its	O
+predicted	O
+molecular	O
+weight	O
+(	O
+EMBO	O
+J	O
+15	O
+:	O
+5738	O
+,	O
+1996	O
+)	O
+,	O
+contains	O
+multiple	O
+structural	O
+domains	O
+including	O
+two	O
+regions	O
+of	O
+seven	O
+internal	O
+repeats	O
+highly	O
+related	O
+to	O
+the	O
+cell	O
+cycle	O
+regulator	O
+RCC1	B-GENE
+,	O
+a	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factor	I-GENE
+for	O
+the	O
+small	B-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+Ran	B-GENE
+,	O
+seven	O
+beta	O
+-	O
+repeat	O
+domains	O
+characteristic	O
+of	O
+the	O
+beta	O
+subunit	O
+of	O
+heterotrimeric	B-GENE
+G	I-GENE
+proteins	I-GENE
+,	O
+three	O
+putative	O
+SH3	B-GENE
+binding	I-GENE
+sites	I-GENE
+,	O
+a	O
+putative	O
+leucine	O
+-	O
+zipper	O
+and	O
+a	O
+carboxy	B-GENE
+-	I-GENE
+terminal	I-GENE
+HECT	I-GENE
+domain	I-GENE
+characteristic	O
+of	O
+E3	B-GENE
+ubiquitin	I-GENE
+-	I-GENE
+protein	I-GENE
+ligases	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+L45	O
+sequence	O
+between	O
+kinase	O
+subdomains	O
+IV	O
+and	O
+V	O
+specifies	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+responsiveness	O
+of	O
+the	O
+type	B-GENE
+I	I-GENE
+receptor	I-GENE
+.	O
+
+The	O
+two	O
+mouse	O
+lines	O
+carrying	O
+the	O
+unfragmented	O
+Hnf3g	B-GENE
+-	O
+lacZ	B-GENE
+YAC	O
+showed	O
+tissue	O
+-	O
+specific	O
+,	O
+copy	O
+number	O
+-	O
+dependent	O
+and	O
+position	O
+-	O
+independent	O
+expression	O
+,	O
+proving	O
+that	O
+170	O
+kb	O
+of	O
+the	O
+Hnf3g	B-GENE
+locus	O
+contain	O
+all	O
+elements	O
+important	O
+in	O
+the	O
+regulation	O
+of	O
+Hnf3g	B-GENE
+.	O
+
+Second	O
+,	O
+plasmid	O
+-	O
+derived	O
+transgenes	O
+and	O
+gene	O
+targeting	O
+of	O
+the	O
+endogenous	B-GENE
+Hnf3g	I-GENE
+gene	I-GENE
+locus	I-GENE
+were	O
+used	O
+to	O
+demonstrate	O
+that	O
+the	O
+3	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+gene	O
+is	O
+necessary	O
+and	O
+sufficient	O
+to	O
+direct	O
+reporter	O
+gene	O
+expression	O
+in	O
+liver	O
+,	O
+pancreas	O
+,	O
+stomach	O
+and	O
+small	O
+intestine	O
+.	O
+
+Here	O
+we	O
+have	O
+tested	O
+the	O
+hypothesis	O
+that	O
+the	O
+short	O
+transcripts	O
+,	O
+or	O
+proteins	O
+translated	O
+from	O
+the	O
+short	O
+transcripts	O
+,	O
+are	O
+also	O
+required	O
+for	O
+respiration	O
+.	O
+
+Upstream	O
+activating	O
+sequences	O
+(	O
+UASs	O
+)	O
+derived	O
+from	O
+known	O
+Ste12p	B-GENE
+-	O
+dependent	O
+genes	O
+have	O
+previously	O
+been	O
+characterized	O
+to	O
+require	O
+either	O
+multiple	O
+PREs	O
+or	O
+a	O
+single	O
+PRE	O
+coupled	O
+to	O
+a	O
+binding	O
+site	O
+for	O
+a	O
+second	O
+protein	O
+.	O
+
+Prominent	O
+protein	O
+kinase	O
+cascades	O
+are	O
+those	O
+that	O
+activate	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinases	I-GENE
+.	O
+
+JNK	B-GENE
+is	O
+additionally	O
+regulated	O
+by	O
+the	O
+Ras	B-GENE
+-	O
+related	O
+G	B-GENE
+proteins	I-GENE
+Rac	B-GENE
+and	O
+Cdc42	B-GENE
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+tested	O
+this	O
+notion	O
+by	O
+using	O
+ligation	O
+-	O
+mediated	O
+PCR	O
+to	O
+assess	O
+the	O
+formation	O
+of	O
+recombination	B-GENE
+-	I-GENE
+activating	I-GENE
+gene	I-GENE
+(	O
+RAG	B-GENE
+)	O
+-	O
+dependent	O
+double	O
+-	O
+strand	O
+breaks	O
+(	O
+DSBs	O
+)	O
+at	O
+RSSs	O
+3	O
+'	O
+of	O
+Ddelta3	B-GENE
+and	O
+5	O
+'	O
+of	O
+Jdelta1	B-GENE
+.	O
+
+Recent	O
+studies	O
+have	O
+demonstrated	O
+that	O
+Cbl	B-GENE
+,	O
+the	O
+120	O
+-	O
+kDa	O
+protein	O
+product	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+cbl	I-GENE
+proto	I-GENE
+-	I-GENE
+oncogene	I-GENE
+,	O
+serves	O
+as	O
+a	O
+substrate	O
+of	O
+a	O
+number	O
+of	O
+receptor	B-GENE
+-	I-GENE
+coupled	I-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+and	O
+forms	O
+complexes	O
+with	O
+SH3	B-GENE
+and	O
+SH2	B-GENE
+domain	O
+-	O
+containing	O
+proteins	O
+,	O
+pointing	O
+to	O
+its	O
+role	O
+in	O
+signal	O
+transduction	O
+.	O
+
+Although	O
+neither	O
+constitutively	O
+activated	O
+MEK	B-GENE
+(	O
+MEK	B-GENE
+-	I-GENE
+2E	I-GENE
+)	O
+nor	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+was	O
+sufficient	O
+individually	O
+to	O
+differentiate	O
+the	O
+H19	O
+-	O
+7	O
+cells	O
+,	O
+coexpression	O
+of	O
+constitutively	O
+activated	O
+MEK	B-GENE
+and	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+induced	O
+neurite	O
+outgrowth	O
+.	O
+
+This	O
+mechanism	O
+is	O
+in	O
+contrast	O
+to	O
+other	O
+cases	O
+of	O
+splicing	O
+regulation	O
+by	O
+PTB	B-GENE
+,	O
+in	O
+which	O
+the	O
+protein	O
+represses	O
+the	O
+splice	O
+site	O
+to	O
+which	O
+it	O
+binds	O
+.	O
+
+While	O
+important	O
+for	O
+ligand	O
+-	O
+dependent	O
+transactivation	O
+,	O
+this	O
+interaction	O
+surface	O
+is	O
+not	O
+directly	O
+involved	O
+in	O
+transrepression	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+.	O
+
+Gal4	B-GENE
+-	O
+Eed	B-GENE
+fusion	O
+protein	O
+represses	O
+transcription	O
+of	O
+a	O
+reporter	O
+gene	O
+driven	O
+by	O
+a	O
+promoter	O
+that	O
+contains	O
+Gal4	B-GENE
+-	I-GENE
+binding	I-GENE
+DNA	I-GENE
+elements	I-GENE
+.	O
+
+In	O
+situ	O
+hybridization	O
+analysis	O
+in	O
+adult	O
+rat	O
+tissue	O
+reveals	O
+good	O
+correlation	O
+with	O
+this	O
+pattern	O
+and	O
+indicates	O
+that	O
+drm	B-GENE
+mRNA	I-GENE
+is	O
+most	O
+highly	O
+expressed	O
+in	O
+nondividing	O
+and	O
+terminally	O
+differentiated	O
+cells	O
+,	O
+such	O
+as	O
+neurons	O
+,	O
+type	O
+1	O
+lung	O
+cells	O
+,	O
+and	O
+goblet	O
+cells	O
+.	O
+
+A	O
+2	O
+years	O
+and	O
+9	O
+months	O
+old	O
+female	O
+patient	O
+,	O
+with	O
+the	O
+diagnosis	O
+of	O
+Weaver	O
+syndrome	O
+is	O
+reported	O
+.	O
+
+Confirming	O
+measures	O
+made	O
+by	O
+nurses	O
+and	O
+additionally	O
+,	O
+ABPM	O
+for	O
+women	O
+,	O
+seem	O
+to	O
+lessen	O
+this	O
+effect	O
+.	O
+
+In	O
+a	O
+series	O
+of	O
+patients	O
+with	O
+neuroinfection	O
+,	O
+Lyme	O
+disease	O
+,	O
+Guillain	O
+Barre	O
+syndrome	O
+,	O
+demyelinization	O
+,	O
+partial	O
+or	O
+generalized	O
+,	O
+epilepsy	O
+,	O
+we	O
+have	O
+investigated	O
+antiphospholipid	O
+antibodies	O
+of	O
+IgG	B-GENE
+and	O
+IgM	B-GENE
+subtypes	O
+,	O
+together	O
+with	O
+anticoagulant	O
+factors	O
+,	O
+member	O
+of	O
+thrombocytes	O
+,	O
+sedimentation	O
+rate	O
+of	O
+erythrocytes	O
+.	O
+
+Second	O
+,	O
+the	O
+membrane	O
+expression	O
+of	O
+alpha	O
+and	O
+beta	O
+subunits	O
+was	O
+mimicked	O
+by	O
+cholesterol	O
+and	O
+17	O
+-	O
+ketocholesterol	O
+,	O
+both	O
+of	O
+which	O
+inhibit	O
+HMG	B-GENE
+-	I-GENE
+CoA	I-GENE
+reductase	I-GENE
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+Lrp	B-GENE
+binds	O
+a	O
+central	O
+palindromic	O
+site	O
+,	O
+interacting	O
+predominantly	O
+with	O
+the	O
+major	O
+groove	O
+of	O
+its	O
+DNA	O
+target	O
+,	O
+and	O
+that	O
+additional	O
+dimers	O
+bind	O
+to	O
+flanking	O
+sites	O
+to	O
+form	O
+a	O
+nucleoprotein	O
+activation	O
+complex	O
+.	O
+
+Sustained	O
+activation	O
+of	O
+p21	B-GENE
+expression	O
+is	O
+proposed	O
+to	O
+be	O
+a	O
+distinguishing	O
+feature	O
+of	O
+the	O
+activity	O
+of	O
+NGF	B-GENE
+that	O
+contributes	O
+to	O
+PC12	O
+growth	O
+arrest	O
+during	O
+differentiation	O
+
+The	O
+remaining	O
+80	O
+patients	O
+underwent	O
+recordings	O
+of	O
+ECG	O
+,	O
+beat	O
+-	O
+to	O
+-	O
+beat	O
+arterial	O
+oxygen	O
+saturation	O
+(	O
+SaO2	O
+)	O
+,	O
+and	O
+respiration	O
+during	O
+both	O
+spontaneous	O
+and	O
+controlled	O
+breathing	O
+.	O
+
+The	O
+mean	O
+total	O
+white	O
+cell	O
+count	O
+increased	O
+from	O
+a	O
+baseline	O
+of	O
+11	O
+.	O
+3	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+L	O
+(	O
+SD	O
+2	O
+.	O
+3	O
+)	O
+to	O
+16	O
+.	O
+2	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+L	O
+(	O
+SD	O
+4	O
+.	O
+6	O
+)	O
+on	O
+day	O
+1	O
+,	O
+normalising	O
+thereafter	O
+.	O
+
+In	O
+all	O
+experimental	O
+eyes	O
+,	O
+there	O
+was	O
+a	O
+marked	O
+reduction	O
+,	O
+but	O
+never	O
+a	O
+complete	O
+absence	O
+of	O
+adrenergic	O
+nerves	O
+in	O
+the	O
+iris	O
+.	O
+
+These	O
+lesions	O
+may	O
+be	O
+treated	O
+by	O
+propranolol	O
+or	O
+phentolamine	O
+.	O
+
+Furthermore	O
+,	O
+ICER	B-GENE
+negatively	O
+autoregulates	O
+the	O
+alternative	O
+promoter	O
+,	O
+thus	O
+generating	O
+a	O
+feedback	O
+loop	O
+.	O
+
+This	O
+night	O
+-	O
+day	O
+oscillation	O
+is	O
+driven	O
+by	O
+the	O
+endogenous	O
+clock	O
+(	O
+located	O
+in	O
+the	O
+suprachiasmatic	O
+nucleus	O
+,	O
+SCN	O
+)	O
+.	O
+
+The	O
+Ogg1	B-GENE
+protein	I-GENE
+efficiently	O
+cleaves	O
+a	O
+DNA	O
+duplex	O
+where	O
+a	O
+preformed	O
+AP	B-GENE
+site	I-GENE
+is	O
+placed	O
+opposite	O
+a	O
+cytosine	O
+(	O
+AP	O
+/	O
+C	O
+)	O
+.	O
+
+A	O
+consensus	O
+sequence	O
+indicates	O
+a	O
+highly	O
+conserved	O
+lysine	O
+residue	O
+,	O
+K120	O
+of	O
+endonuclease	B-GENE
+III	I-GENE
+or	O
+K241	O
+of	O
+Ogg1	B-GENE
+,	O
+respectively	O
+.	O
+
+Overall	O
+,	O
+these	O
+findings	O
+demonstrate	O
+that	O
+mutations	O
+E768D	O
+and	O
+V804L	O
+are	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+mutations	O
+that	O
+confer	O
+to	O
+the	O
+long	B-GENE
+RET	I-GENE
+isoform	I-GENE
+the	O
+capacity	O
+to	O
+exert	O
+a	O
+biological	O
+effect	O
+,	O
+although	O
+these	O
+mutations	O
+are	O
+more	O
+weakly	O
+activating	O
+than	O
+the	O
+MEN2A	B-GENE
+and	O
+MEN2B	B-GENE
+mutations	O
+.	O
+
+Volunteers	O
+were	O
+irradiated	O
+on	O
+their	O
+backs	O
+with	O
+suberythemal	O
+UV	O
+daily	O
+for	O
+5	O
+d	O
+after	O
+application	O
+of	O
+the	O
+sunscreens	O
+and	O
+their	O
+base	O
+lotion	O
+to	O
+different	O
+sites	O
+.	O
+
+E2F	B-GENE
+is	O
+a	O
+heterodimeric	O
+complex	O
+consisting	O
+of	O
+E2F	B-GENE
+family	I-GENE
+members	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+5	I-GENE
+)	I-GENE
+and	O
+DP	B-GENE
+proteins	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+3	I-GENE
+)	I-GENE
+.	O
+
+EBER1	B-GENE
+mRNA	I-GENE
+,	O
+a	O
+consistent	O
+marker	O
+of	O
+viral	O
+latency	O
+,	O
+was	O
+positive	O
+in	O
+all	O
+PEL	O
+cases	O
+,	O
+although	O
+at	O
+lower	O
+levels	O
+than	O
+in	O
+the	O
+non	O
+-	O
+PEL	O
+controls	O
+due	O
+to	O
+EBER1	B-GENE
+expression	O
+by	O
+only	O
+a	O
+variable	O
+subset	O
+of	O
+lymphoma	O
+cells	O
+.	O
+
+METHODS	O
+:	O
+Four	O
+hundred	O
+fifty	O
+patients	O
+with	O
+the	O
+diagnosis	O
+of	O
+squamous	O
+cell	O
+carcinoma	O
+of	O
+the	O
+oral	O
+cavity	O
+received	O
+their	O
+primary	O
+treatment	O
+at	O
+Roswell	O
+Park	O
+Cancer	O
+Center	O
+(	O
+RPCI	O
+)	O
+from	O
+1971	O
+to	O
+1991	O
+.	O
+
+Therefore	O
+,	O
+use	O
+of	O
+presaturation	O
+is	O
+recommended	O
+for	O
+myocardial	O
+motion	O
+studies	O
+using	O
+cine	O
+PC	O
+velocity	O
+data	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+DNA	O
+-	O
+binding	O
+experiments	O
+show	O
+that	O
+either	O
+one	O
+of	O
+the	O
+two	O
+MADS	B-GENE
+domains	I-GENE
+of	O
+a	O
+dimer	O
+can	O
+be	O
+sufficient	O
+to	O
+confer	O
+a	O
+particular	O
+DNA	O
+-	O
+binding	O
+specificity	O
+to	O
+the	O
+complex	O
+and	O
+that	O
+sequences	O
+outside	O
+the	O
+amino	O
+-	O
+terminal	O
+basic	O
+region	O
+of	O
+the	O
+MADS	B-GENE
+domain	O
+can	O
+,	O
+in	O
+some	O
+cases	O
+,	O
+contribute	O
+to	O
+the	O
+DNA	O
+-	O
+binding	O
+specificity	O
+of	O
+the	O
+proteins	O
+.	O
+
+PURPOSE	O
+/	O
+OBJECTIVES	O
+:	O
+To	O
+examine	O
+the	O
+question	O
+of	O
+whether	O
+an	O
+early	O
+first	O
+full	O
+-	O
+term	O
+pregnancy	O
+(	O
+FFTP	O
+)	O
+protects	O
+against	O
+breast	O
+cancer	O
+and	O
+whether	O
+interruption	O
+of	O
+the	O
+pregnancy	O
+with	O
+an	O
+induced	O
+abortion	O
+increases	O
+breast	O
+cancer	O
+risk	O
+.	O
+
+Two	O
+related	O
+studies	O
+conducted	O
+over	O
+a	O
+five	O
+week	O
+period	O
+measured	O
+and	O
+typed	O
+HLA	B-GENE
+-	I-GENE
+DQA1	I-GENE
+from	O
+accumulated	O
+DNA	O
+on	O
+autopsy	O
+room	O
+and	O
+Forensic	O
+DNA	O
+Laboratory	O
+structures	O
+.	O
+
+Thirty	O
+-	O
+two	O
+rats	O
+were	O
+divided	O
+into	O
+four	O
+groups	O
+.	O
+
+Mutagenesis	O
+of	O
+the	O
+pecT	B-GENE
+regulatory	O
+region	O
+revealed	O
+the	O
+presence	O
+of	O
+two	O
+sites	O
+in	O
+which	O
+insertions	O
+reproduced	O
+the	O
+pec	B-GENE
+-	I-GENE
+1	I-GENE
+phenotype	O
+.	O
+
+BRCA1	B-GENE
+,	O
+a	O
+familial	O
+breast	O
+and	O
+ovarian	O
+cancer	O
+susceptibility	O
+gene	O
+encodes	O
+nuclear	O
+phosphoproteins	O
+that	O
+function	O
+as	O
+tumor	O
+suppressors	O
+in	O
+human	O
+breast	O
+cancer	O
+cells	O
+.	O
+
+The	O
+alternative	O
+splice	O
+sites	O
+for	O
+the	O
+smallest	O
+adducin	B-GENE
+isoform	O
+,	O
+beta	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+are	O
+alternative	O
+donor	O
+and	O
+acceptor	O
+sites	O
+within	O
+exons	O
+7	O
+and	O
+12	O
+.	O
+
+Two	O
+new	O
+temperature	O
+-	O
+sensitive	O
+alleles	O
+of	O
+SEC3	B-GENE
+,	O
+1	O
+of	O
+10	O
+late	O
+-	O
+acting	O
+SEC	B-GENE
+genes	I-GENE
+required	O
+for	O
+targeting	O
+or	O
+fusion	O
+of	O
+post	O
+-	O
+Golgi	O
+secretory	O
+vesicles	O
+to	O
+the	O
+plasma	O
+membrane	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+were	O
+isolated	O
+in	O
+a	O
+screen	O
+for	O
+temperature	O
+-	O
+sensitive	O
+secretory	O
+mutants	O
+that	O
+are	O
+synthetically	O
+lethal	O
+with	O
+sec4	B-GENE
+-	I-GENE
+8	I-GENE
+.	O
+
+Cell	O
+49	O
+,	O
+753	O
+-	O
+761	O
+]	O
+.	O
+
+Twenty	O
+-	O
+one	O
+ELISA	O
+-	O
+positive	O
+sera	O
+were	O
+tested	O
+and	O
+confirmed	O
+positive	O
+by	O
+plaque	O
+reduction	O
+neutralization	O
+testing	O
+.	O
+
+Patients	O
+received	O
+either	O
+diltiazem	O
+CD	O
+180	O
+mg	O
+or	O
+placebo	O
+once	O
+/	O
+day	O
+in	O
+combination	O
+with	O
+existing	O
+antianginal	O
+therapy	O
+.	O
+
+Reactive	O
+lymphoid	O
+hyperplasia	O
+was	O
+found	O
+in	O
+15	O
+cases	O
+,	O
+2	O
+cases	O
+had	O
+angiofollicular	O
+lymphoid	O
+hyperplasia	O
+or	O
+Castleman	O
+'	O
+s	O
+disease	O
+,	O
+atypical	O
+lymphoid	O
+hyperplasia	O
+suggestive	O
+of	O
+malignant	O
+lymphoma	O
+was	O
+observed	O
+in	O
+3	O
+cases	O
+,	O
+and	O
+malignant	O
+lymphoma	O
+was	O
+diagnosed	O
+in	O
+the	O
+remaining	O
+4	O
+cases	O
+.	O
+
+Tyrosine	O
+1356	O
+forms	O
+a	O
+multisubstrate	O
+binding	O
+site	O
+for	O
+the	O
+Grb2	B-GENE
+and	O
+Shc	B-GENE
+adaptor	I-GENE
+proteins	I-GENE
+,	O
+the	O
+p85	B-GENE
+subunit	I-GENE
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+'	I-GENE
+-	I-GENE
+kinase	I-GENE
+,	O
+phospholipase	B-GENE
+Cgamma	I-GENE
+,	O
+and	O
+a	O
+phosphatase	O
+,	O
+SHP2	B-GENE
+.	O
+
+Then	O
+we	O
+correlated	O
+HRCT	O
+findings	O
+with	O
+the	O
+clinical	O
+features	O
+,	O
+pulmonary	O
+functions	O
+and	O
+methacholine	O
+PC20	O
+(	O
+PC20M	O
+)	O
+and	O
+studied	O
+their	O
+clinical	O
+significance	O
+.	O
+
+Gtx	B-GENE
+mRNA	I-GENE
+accumulates	O
+in	O
+parallel	O
+with	O
+the	O
+RNAs	O
+encoding	O
+the	O
+major	O
+structural	O
+proteins	O
+of	O
+myelin	O
+,	O
+myelin	B-GENE
+basic	I-GENE
+protein	I-GENE
+(	O
+MBP	B-GENE
+)	O
+,	O
+and	O
+proteolipid	B-GENE
+protein	I-GENE
+(	O
+PLP	B-GENE
+)	O
+during	O
+postnatal	O
+brain	O
+development	O
+;	O
+Gtx	B-GENE
+mRNA	I-GENE
+decreases	O
+in	O
+parallel	O
+with	O
+MBP	B-GENE
+and	O
+PLP	B-GENE
+mRNAs	I-GENE
+in	O
+the	O
+brains	O
+of	O
+myelin	O
+-	O
+deficient	O
+rats	O
+,	O
+which	O
+have	O
+a	O
+point	O
+mutation	O
+in	O
+the	O
+PLP	B-GENE
+gene	I-GENE
+.	O
+
+Contacts	O
+between	O
+Bacillus	O
+subtilis	O
+catabolite	O
+regulatory	O
+protein	O
+CcpA	B-GENE
+and	O
+amyO	B-GENE
+target	O
+site	O
+.	O
+
+They	O
+also	O
+interact	O
+with	O
+GTPase	B-GENE
+activating	I-GENE
+proteins	I-GENE
+encoded	O
+by	O
+IRA1	B-GENE
+and	O
+IRA2	B-GENE
+.	O
+
+For	O
+E2	O
+,	O
+each	O
+cat	O
+was	O
+given	O
+either	O
+5	O
+(	O
+group	O
+[	O
+G	O
+]	O
+1	O
+)	O
+or	O
+10	O
+(	O
+G2	O
+)	O
+mg	O
+of	O
+itraconazole	O
+/	O
+kg	O
+(	O
+capsules	O
+)	O
+twice	O
+daily	O
+for	O
+6	O
+weeks	O
+.	O
+
+RESULTS	O
+:	O
+For	O
+E1	O
+,	O
+itraconazole	O
+plasma	O
+drug	O
+concentration	O
+extrapolated	O
+to	O
+time	O
+zero	O
+(	O
+IV	O
+dose	O
+)	O
+was	O
+5	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+micrograms	O
+/	O
+ml	O
+,	O
+and	O
+mean	O
+residence	O
+time	O
+(	O
+MRT	O
+)	O
+was	O
+37	O
++	O
+/	O
+-	O
+16	O
+hours	O
+.	O
+
+The	O
+human	O
+U4	B-GENE
+/	O
+U6	B-GENE
+snRNP	O
+contains	O
+60	O
+and	O
+90kD	O
+proteins	O
+that	O
+are	O
+structurally	O
+homologous	O
+to	O
+the	O
+yeast	O
+splicing	O
+factors	O
+Prp4p	B-GENE
+and	O
+Prp3p	B-GENE
+.	O
+
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+was	O
+started	O
+on	O
+day	O
+3	O
+of	O
+each	O
+cycle	O
+(	O
+5	O
+microg	O
+/	O
+kg	O
+/	O
+day	O
+)	O
+and	O
+was	O
+stopped	O
+the	O
+day	O
+before	O
+the	O
+last	O
+apheresis	O
+or	O
+when	O
+absolute	O
+neutrophil	O
+count	O
+was	O
+above	O
+0	O
+.	O
+5	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+l	O
+.	O
+
+Supershift	O
+assays	O
+,	O
+using	O
+Jun	B-GENE
+and	I-GENE
+Fos	I-GENE
+family	I-GENE
+member	I-GENE
+-	I-GENE
+specific	I-GENE
+antibodies	I-GENE
+,	O
+showed	O
+that	O
+protein	O
+complexes	O
+formed	O
+by	O
+AtT	O
+-	O
+20	O
+cell	O
+nuclear	O
+extracts	O
+bound	O
+to	O
+the	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+were	O
+comprised	O
+of	O
+Jun	B-GENE
+family	O
+members	O
+,	O
+JunD	B-GENE
+,	O
+JunB	B-GENE
+,	O
+and	O
+cJun	B-GENE
+.	O
+
+The	O
+majority	O
+of	O
+PI	B-GENE
+kinase	I-GENE
+activity	O
+appeared	O
+to	O
+be	O
+cbl	B-GENE
+-	O
+associated	O
+after	O
+PRL	B-GENE
+stimulation	O
+.	O
+
+Mutation	O
+of	O
+Enh4	B-GENE
+,	O
+an	O
+essential	O
+GT	B-GENE
+-	I-GENE
+IIC	I-GENE
+-	I-GENE
+like	I-GENE
+enhanson	I-GENE
+in	O
+the	O
+context	O
+of	O
+the	O
+intact	O
+enhancer	O
+,	O
+abolishes	O
+silencer	O
+activity	O
+,	O
+and	O
+multimerized	O
+GT	B-GENE
+-	I-GENE
+IIC	I-GENE
+enhansons	I-GENE
+mimic	O
+the	O
+intact	O
+CSEn	B-GENE
+enhancer	I-GENE
+/	I-GENE
+silencer	I-GENE
+activities	O
+in	O
+BeWo	O
+and	O
+GC	O
+cells	O
+,	O
+respectively	O
+.	O
+
+Using	O
+lectin	B-GENE
+-	O
+affinity	O
+chromatography	O
+,	O
+discordance	O
+between	O
+the	O
+pattern	O
+of	O
+O	O
+-	O
+glycosylation	O
+of	O
+SSBP	B-GENE
+and	O
+DSBP	B-GENE
+was	O
+demonstrated	O
+.	O
+
+Deletion	O
+mapping	O
+experiments	O
+determined	O
+that	O
+the	O
+sequences	O
+required	O
+for	O
+full	O
+activity	O
+in	O
+MSC	O
+-	O
+1	O
+cells	O
+were	O
+included	O
+within	O
+619	O
+bp	O
+of	O
+the	O
+start	O
+site	O
+and	O
+identified	O
+several	O
+regions	O
+that	O
+demonstrated	O
+increased	O
+luciferase	B-GENE
+activity	O
+:	O
+the	O
+-	O
+583	O
+bp	O
+to	O
+-	O
+564	O
+bp	O
+,	O
+-	O
+503	O
+bp	O
+to	O
+-	O
+484	O
+bp	O
+,	O
+and	O
+-	O
+114	O
+bp	O
+to	O
+-	O
+65	O
+regions	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+PH	B-GENE
+and	O
+PTB	O
+domains	O
+are	O
+highly	O
+homologous	O
+(	O
+at	O
+least	O
+40	O
+%	O
+identical	O
+)	O
+to	O
+those	O
+found	O
+in	O
+insulin	B-GENE
+receptor	I-GENE
+substrates	I-GENE
+1	I-GENE
+,	I-GENE
+2	I-GENE
+,	I-GENE
+and	I-GENE
+3	I-GENE
+(	O
+IRS	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+IRS	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+and	O
+IRS	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+.	O
+
+The	O
+mouse	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+2	I-GENE
+gene	I-GENE
+.	O
+
+As	O
+demonstrated	O
+by	O
+gel	O
+mobility	O
+shift	O
+analysis	O
+and	O
+supershift	O
+experiments	O
+,	O
+FIRE1	B-GENE
+,	O
+located	O
+between	O
+-	O
+516	O
+and	O
+-	O
+498	O
+,	O
+is	O
+responsible	O
+for	O
+binding	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+.	O
+
+MR	O
+imaging	O
+of	O
+traumatic	O
+head	O
+injuries	O
+using	O
+FLAIR	O
+technique	O
+
+Gag	B-GENE
+protein	O
+sequence	O
+motifs	O
+of	O
+the	O
+NC	B-GENE
+domain	I-GENE
+of	O
+primate	O
+foamy	O
+viruses	O
+assumed	O
+to	O
+be	O
+involved	O
+in	O
+genome	O
+encapsidation	O
+are	O
+not	O
+conserved	O
+in	O
+FeFV	O
+.	O
+
+Induction	O
+of	O
+B	O
+cell	O
+apoptosis	O
+by	O
+co	O
+-	O
+cross	O
+-	O
+linking	O
+CD23	B-GENE
+and	O
+sIg	B-GENE
+involves	O
+aberrant	O
+regulation	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+and	O
+is	O
+inhibited	O
+by	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+theoretical	O
+models	O
+for	O
+the	O
+Gla	O
+and	O
+EGF	B-GENE
+-	I-GENE
+1	I-GENE
+modules	I-GENE
+of	O
+human	B-GENE
+PS	I-GENE
+constructed	O
+using	O
+prothrombin	B-GENE
+and	O
+factor	B-GENE
+X	I-GENE
+experimental	O
+structures	O
+.	O
+
+The	O
+Cut9	B-GENE
+subunit	I-GENE
+is	O
+likely	O
+to	O
+be	O
+a	O
+target	O
+for	O
+regulating	O
+APC	B-GENE
+/	I-GENE
+cyclosome	I-GENE
+function	O
+through	O
+protein	O
+-	O
+protein	O
+interactions	O
+and	O
+phosphorylation	O
+.	O
+
+The	O
+dose	O
+was	O
+50	O
+Gy	O
+/	O
+20	O
+fractions	O
+/	O
+5	O
+weeks	O
+.	O
+
+All	O
+the	O
+women	O
+received	O
+13	O
+.	O
+5	O
+mg	O
+plain	O
+bupivacaine	O
+via	O
+subarachnoid	O
+injection	O
+at	O
+the	O
+L2	O
+-	O
+3	O
+interspace	O
+.	O
+
+Far	O
+from	O
+this	O
+being	O
+the	O
+case	O
+,	O
+however	O
+,	O
+the	O
+measurement	O
+of	O
+apo	B-GENE
+B	I-GENE
+has	O
+met	O
+every	O
+reasonable	O
+standard	O
+of	O
+laboratory	O
+precision	O
+and	O
+reliability	O
+to	O
+allow	O
+its	O
+widespread	O
+introduction	O
+in	O
+clinical	O
+laboratories	O
+.	O
+
+Two	O
+soybean	O
+cDNA	O
+clones	O
+,	O
+SPK	B-GENE
+-	I-GENE
+3	I-GENE
+and	O
+SPK	B-GENE
+-	I-GENE
+4	I-GENE
+,	O
+encoding	O
+putative	O
+protein	O
+kinases	O
+were	O
+isolated	O
+and	O
+characterized	O
+.	O
+
+Genes	O
+belonging	O
+to	O
+the	O
+ras	B-GENE
+superfamily	I-GENE
+encode	O
+low	B-GENE
+-	I-GENE
+molecular	I-GENE
+-	I-GENE
+weight	I-GENE
+GTP	I-GENE
+/	I-GENE
+GDP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+that	O
+are	O
+highly	O
+conserved	O
+in	O
+wide	O
+variety	O
+of	O
+organisms	O
+.	O
+
+Ent	B-GENE
+-	I-GENE
+kaurene	I-GENE
+synthase	I-GENE
+from	I-GENE
+the	I-GENE
+fungus	I-GENE
+Phaeosphaeria	I-GENE
+sp	O
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+identify	O
+and	O
+characterize	O
+two	O
+overlapping	O
+ELL	B-GENE
+functional	I-GENE
+domains	I-GENE
+that	O
+govern	O
+its	O
+interaction	O
+with	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+and	O
+the	O
+ternary	O
+elongation	O
+complex	O
+.	O
+
+Eight	O
+induced	O
+cDNA	O
+sequences	O
+were	O
+identified	O
+and	O
+designated	O
+message	B-GENE
+up	I-GENE
+-	I-GENE
+regulated	I-GENE
+during	I-GENE
+death	I-GENE
+(	B-GENE
+mud	I-GENE
+)	I-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+8	I-GENE
+.	O
+
+The	O
+position	O
+,	O
+transcription	O
+orientation	O
+,	O
+and	O
+imprinted	O
+status	O
+of	O
+the	O
+genes	O
+immediately	O
+flanking	O
+Igf2r	B-GENE
+have	O
+been	O
+assessed	O
+.	O
+
+Here	O
+,	O
+we	O
+describe	O
+directional	O
+chromosome	O
+walking	O
+studies	O
+starting	O
+from	O
+D8S260	B-GENE
+as	O
+well	O
+as	O
+D8S285	B-GENE
+.	O
+
+We	O
+describe	O
+a	O
+novel	O
+zinc	B-GENE
+finger	I-GENE
+protein	I-GENE
+,	O
+dsRBP	B-GENE
+-	I-GENE
+ZFa	I-GENE
+,	O
+isolated	O
+by	O
+screening	O
+an	O
+expression	O
+library	O
+with	O
+dsRNA	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+the	O
+retroplasmid	O
+reverse	B-GENE
+transcriptase	I-GENE
+is	O
+uniquely	O
+adapted	O
+to	O
+initiate	O
+cDNA	O
+synthesis	O
+by	O
+recognizing	O
+a	O
+3	O
+'	O
+CCA	O
+sequence	O
+.	O
+
+Nasal	O
+absorption	O
+was	O
+rapid	O
+,	O
+nasal	O
+bioavailability	O
+was	O
+43	O
+%	O
+,	O
+and	O
+the	O
+iv	O
+and	O
+nasal	O
+elimination	O
+profiles	O
+were	O
+similar	O
+.	O
+
+Together	O
+,	O
+these	O
+results	O
+suggest	O
+that	O
+EGF	B-GENE
+/	O
+Ras	B-GENE
+/	O
+Raf	B-GENE
+induces	O
+transcription	O
+via	O
+combined	O
+activation	O
+of	O
+ATF3	B-GENE
+/	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+and	O
+a	O
+52	O
+-	O
+kDa	O
+nuclear	O
+factor	O
+,	O
+whereas	O
+JunD	B-GENE
+acts	O
+as	O
+a	O
+repressor	O
+of	O
+this	O
+response	O
+.	O
+
+Together	O
+,	O
+these	O
+data	O
+support	O
+a	O
+model	O
+in	O
+which	O
+Tax	B-GENE
+anchors	O
+CBP	B-GENE
+to	O
+the	O
+HTLV	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+,	O
+with	O
+strong	O
+transcriptional	O
+activation	O
+resulting	O
+from	O
+the	O
+CBP	B-GENE
+-	O
+associated	O
+activities	O
+of	O
+nucleosome	O
+remodeling	O
+and	O
+recruitment	O
+of	O
+the	O
+general	O
+transcription	O
+machinery	O
+.	O
+
+DNase	B-GENE
+I	I-GENE
+and	O
+1	O
+,	O
+10	O
+-	O
+phenanthroline	O
+-	O
+copper	O
+footprinting	O
+of	O
+MURA	B-GENE
+-	O
+Mu1	B-GENE
+TIR	O
+complexes	O
+indicate	O
+that	O
+MURA	B-GENE
+binds	O
+to	O
+a	O
+conserved	O
+approximately	O
+32	O
+-	O
+bp	O
+region	O
+in	O
+the	O
+TIR	O
+of	O
+Mu1	B-GENE
+.	O
+
+Various	O
+assays	O
+demonstrate	O
+promoter	O
+activity	O
+in	O
+this	O
+sequence	O
+that	O
+reproduces	O
+the	O
+normal	O
+control	O
+of	O
+E2F2	B-GENE
+expression	O
+during	O
+a	O
+growth	O
+stimulation	O
+.	O
+
+In	O
+the	O
+adult	O
+mouse	O
+,	O
+ERR	B-GENE
+alpha	I-GENE
+is	O
+most	O
+highly	O
+expressed	O
+in	O
+kidney	O
+,	O
+heart	O
+,	O
+and	O
+brown	O
+adipocytes	O
+,	O
+tissues	O
+which	O
+preferentially	O
+metabolize	O
+fatty	O
+acids	O
+.	O
+
+The	O
+MCAD	B-GENE
+nuclear	I-GENE
+receptor	I-GENE
+response	I-GENE
+element	I-GENE
+1	I-GENE
+(	O
+NRRE	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+interacts	O
+in	O
+vitro	O
+with	O
+ERR	B-GENE
+alpha	I-GENE
+expressed	O
+in	O
+COS	O
+-	O
+7	O
+cells	O
+.	O
+
+Mapping	O
+features	O
+of	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+integrase	I-GENE
+near	O
+selected	O
+sites	O
+on	O
+viral	O
+and	O
+target	O
+DNA	O
+molecules	O
+in	O
+an	O
+active	O
+enzyme	O
+-	O
+DNA	O
+complex	O
+by	O
+photo	O
+-	O
+cross	O
+-	O
+linking	O
+.	O
+
+The	O
+complete	O
+response	O
+(	O
+CR	O
+)	O
+rate	O
+was	O
+34	O
+%	O
+in	O
+the	O
+CODE	O
+with	O
+rhG	B-GENE
+-	I-GENE
+CSF	I-GENE
+group	O
+and	O
+23	O
+%	O
+in	O
+the	O
+CODE	O
+alone	O
+group	O
+;	O
+the	O
+median	O
+survival	O
+was	O
+59	O
+and	O
+32	O
+weeks	O
+,	O
+respectively	O
+,	O
+in	O
+these	O
+groups	O
+(	O
+P	O
+=	O
+0	O
+.	O
+004	O
+)	O
+.	O
+
+Heterogeneous	B-GENE
+nuclear	I-GENE
+ribonucleoprotein	I-GENE
+A1	I-GENE
+binds	O
+to	O
+the	O
+transcription	O
+-	O
+regulatory	O
+region	O
+of	O
+mouse	O
+hepatitis	O
+virus	O
+RNA	O
+.	O
+
+In	O
+the	O
+first	O
+part	O
+of	O
+our	O
+study	O
+,	O
+the	O
+highest	O
+mutagenicity	O
+was	O
+revealed	O
+by	O
+TA98	O
+strain	O
+without	O
+enzymatic	O
+activation	O
+,	O
+suggesting	O
+a	O
+direct	O
+-	O
+acting	O
+mutagenicity	O
+prevalence	O
+in	O
+diesel	O
+particulate	O
+.	O
+
+The	O
+addition	O
+of	O
+culture	O
+to	O
+the	O
+CC	O
+and	O
+CC	O
+:	O
+SW	O
+by	O
+-	O
+products	O
+resulted	O
+in	O
+pH	O
+values	O
+lower	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+than	O
+those	O
+without	O
+culture	O
+on	O
+Day	O
+21	O
+,	O
+and	O
+the	O
+15	O
+%	O
+carbohydrate	O
+treatment	O
+significantly	O
+reduced	O
+pH	O
+beyond	O
+the	O
+5	O
+%	O
+carbohydrate	O
+.	O
+
+Myocardial	O
+interstitial	O
+edema	O
+is	O
+more	O
+likely	O
+a	O
+potential	O
+mechanism	O
+of	O
+diastolic	O
+dysfunction	O
+after	O
+DC	O
+shocks	O
+.	O
+
+Two	O
+experiments	O
+(	O
+N	O
+=	O
+20	O
+each	O
+)	O
+were	O
+carried	O
+out	O
+to	O
+explore	O
+the	O
+nature	O
+of	O
+ERP	O
+negativities	O
+in	O
+a	O
+visuospatial	O
+memory	O
+task	O
+and	O
+in	O
+an	O
+auditory	O
+spatial	O
+memory	O
+task	O
+,	O
+respectively	O
+.	O
+
+Biol	O
+.	O
+
+The	O
+pattern	O
+and	O
+timing	O
+of	O
+CARP	B-GENE
+mRNA	I-GENE
+expression	O
+,	O
+including	O
+transient	O
+expression	O
+in	O
+the	O
+tongue	O
+at	O
+14	O
+.	O
+5	O
+days	O
+p	O
+.	O
+c	O
+.	O
+,	O
+coincides	O
+with	O
+that	O
+of	O
+Nkx2	B-GENE
+.	I-GENE
+5	I-GENE
+/	O
+Csx	B-GENE
+(	O
+a	O
+putative	O
+homolog	O
+of	O
+tinman	B-GENE
+,	O
+the	O
+Drosophila	O
+melanogaster	O
+gene	O
+responsible	O
+for	O
+cardiac	O
+development	O
+)	O
+.	O
+
+Overexpression	O
+of	O
+CARP	B-GENE
+in	O
+cardiomyocytes	O
+suppresses	O
+cardiac	B-GENE
+troponin	I-GENE
+C	I-GENE
+and	O
+atrial	B-GENE
+natriuretic	I-GENE
+factor	I-GENE
+transcription	O
+.	O
+
+Substrate	O
+specificity	O
+of	O
+the	O
+RNase	B-GENE
+activity	O
+of	O
+yeast	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+III	I-GENE
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+and	O
+competition	O
+experiments	O
+showed	O
+that	O
+site	O
+A	O
+is	O
+recognized	O
+by	O
+an	O
+NF1	B-GENE
+protein	I-GENE
+.	O
+
+Examination	O
+of	O
+the	O
+MMP	B-GENE
+-	I-GENE
+2	I-GENE
+RE1	I-GENE
+sequence	I-GENE
+revealed	O
+an	O
+incomplete	O
+Y	O
+-	O
+box	O
+sequence	O
+(	O
+CTGCTGGGCAAG	O
+)	O
+,	O
+which	O
+specifically	O
+interacted	O
+with	O
+recombinant	B-GENE
+YB	I-GENE
+-	I-GENE
+1	I-GENE
+on	O
+DMS	O
+protection	O
+footprinting	O
+analysis	O
+.	O
+
+Hence	O
+,	O
+scs32	B-GENE
+only	O
+partially	O
+suppressed	O
+the	O
+ts	O
+phenotype	O
+and	O
+was	O
+unable	O
+to	O
+suppress	O
+the	O
+Ino	O
+-	O
+phenotype	O
+of	O
+rpo26	B-GENE
+-	I-GENE
+31	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+both	O
+Sp1	B-GENE
+and	O
+ETS	B-GENE
+proteins	I-GENE
+are	O
+required	O
+to	O
+bring	O
+about	O
+full	O
+promoter	O
+activity	O
+in	O
+the	O
+Surf	B-GENE
+-	I-GENE
+1	I-GENE
+direction	O
+.	O
+
+We	O
+have	O
+subcloned	O
+into	O
+pBR322	O
+deoxyribonucleic	O
+acid	O
+(	O
+DNA	O
+)	O
+sequences	O
+mapping	O
+either	O
+in	O
+the	O
+coding	O
+region	O
+,	O
+the	O
+5	O
+'	O
+spacer	O
+,	O
+or	O
+the	O
+3	O
+'	O
+spacer	O
+of	O
+the	O
+H2B	B-GENE
+histone	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+combination	O
+of	O
+hydralazine	O
+hydrochloride	O
+and	O
+isosorbide	O
+dinitrate	O
+also	O
+improves	O
+survival	O
+,	O
+but	O
+direct	O
+comparison	O
+of	O
+both	O
+regimens	O
+provided	O
+evidence	O
+for	O
+a	O
+less	O
+favourable	O
+effect	O
+than	O
+that	O
+of	O
+the	O
+ACE	B-GENE
+inhibitors	O
+.	O
+
+To	O
+address	O
+mechanisms	O
+that	O
+define	O
+interactions	O
+of	O
+Site	B-GENE
+II	I-GENE
+regulatory	I-GENE
+factors	I-GENE
+with	O
+this	O
+cell	O
+cycle	O
+control	O
+element	O
+,	O
+we	O
+have	O
+investigated	O
+these	O
+determinants	O
+of	O
+transcriptional	O
+regulation	O
+at	O
+the	O
+G1	O
+/	O
+S	O
+phase	O
+transition	O
+in	O
+FDC	O
+-	O
+P1	O
+hematopoietic	O
+progenitor	O
+cells	O
+.	O
+
+The	O
+goal	O
+of	O
+this	O
+study	O
+was	O
+to	O
+identify	O
+neuronal	O
+cell	O
+cultures	O
+that	O
+express	O
+RC3	B-GENE
+/	O
+neurogranin	B-GENE
+,	O
+to	O
+check	O
+whether	O
+they	O
+are	O
+sensitive	O
+to	O
+T3	O
+,	O
+and	O
+to	O
+examine	O
+the	O
+mechanism	O
+of	O
+regulation	O
+.	O
+
+Their	O
+circadian	O
+responses	O
+to	O
+both	O
+photic	O
+and	O
+non	O
+-	O
+photic	O
+cues	O
+were	O
+then	O
+tested	O
+.	O
+
+Human	B-GENE
+Duo	I-GENE
+contains	O
+a	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factor	I-GENE
+(	O
+GEF	B-GENE
+)	O
+domain	O
+that	O
+is	O
+likely	O
+to	O
+be	O
+rac1	B-GENE
+-	O
+specific	O
+,	O
+a	O
+pleckstrin	B-GENE
+homology	I-GENE
+(	O
+PH	B-GENE
+)	O
+domain	O
+and	O
+spectrin	B-GENE
+-	I-GENE
+like	I-GENE
+repeat	I-GENE
+units	I-GENE
+.	O
+
+ArgR	B-GENE
+was	O
+shown	O
+to	O
+be	O
+a	O
+dimer	O
+of	O
+two	O
+equal	O
+subunits	O
+,	O
+each	O
+with	O
+a	O
+molecular	O
+mass	O
+of	O
+37	O
+,	O
+000	O
+Da	O
+.	O
+
+Plasma	B-GENE
+leptin	I-GENE
+concentrations	O
+were	O
+higher	O
+in	O
+women	O
+than	O
+men	O
+,	O
+even	O
+after	O
+the	O
+adjustment	O
+for	O
+differences	O
+in	O
+fat	O
+mass	O
+(	O
+28	O
++	O
+/	O
+-	O
+3	O
+ng	O
+/	O
+ml	O
+for	O
+women	O
+vs	O
+.	O
+
+Consistent	O
+with	O
+effects	O
+on	O
+STAT	B-GENE
+activation	O
+,	O
+altered	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+also	O
+affected	O
+EGF	B-GENE
+-	O
+induced	O
+activation	O
+of	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+pathway	O
+;	O
+expression	O
+of	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+(	I-GENE
+Cys	I-GENE
+-	I-GENE
+-	I-GENE
+>	I-GENE
+Ser	I-GENE
+)	I-GENE
+inhibited	O
+activity	O
+of	O
+MEK	B-GENE
+by	O
+approximately	O
+25	O
+%	O
+,	O
+whereas	O
+expression	O
+of	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+resulted	O
+in	O
+a	O
+approximately	O
+25	O
+%	O
+increase	O
+.	O
+
+This	O
+interaction	O
+involved	O
+the	O
+SH3	B-GENE
+region	I-GENE
+of	O
+p50	B-GENE
+(	O
+csk	B-GENE
+)	O
+and	O
+a	O
+proline	O
+-	O
+rich	O
+region	O
+(	O
+PPPLPERTPESFVLADM	O
+)	O
+outside	O
+the	O
+catalytic	O
+region	O
+of	O
+PTP	B-GENE
+-	O
+PEST	O
+.	O
+
+Following	O
+2	O
+.	O
+5	O
+Gy	O
+,	O
+HbO2	B-GENE
+changes	O
+were	O
+minimal	O
+.	O
+
+Among	O
+38	O
+patients	O
+with	O
+inducible	O
+reentrant	O
+VTs	O
+who	O
+underwent	O
+electrophysiologic	O
+study	O
+(	O
+EPS	O
+)	O
+,	O
+10	O
+VTs	O
+of	O
+six	O
+patients	O
+were	O
+selected	O
+.	O
+
+The	O
+cycle	O
+length	O
+of	O
+induced	O
+VT	O
+(	O
+n	O
+=	O
+10	O
+VTs	O
+)	O
+was	O
+380	O
++	O
+/	O
+-	O
+41	O
+msec	O
+.	O
+
+Transient	O
+hyperammonaemia	O
+in	O
+an	O
+adult	O
+German	O
+shepherd	O
+dog	O
+.	O
+
+We	O
+established	O
+that	O
+the	O
+2	O
+.	O
+6	O
+kb	O
+mRNA	O
+V	O
+-	O
+1	O
+and	O
+the	O
+2	O
+.	O
+3	O
+kb	O
+GGT	B-GENE
+mRNA	O
+V	O
+-	O
+2	O
+derive	O
+,	O
+by	O
+alternate	O
+splicing	O
+,	O
+from	O
+a	O
+primary	O
+transcript	O
+initiated	O
+on	O
+a	O
+distal	O
+promoter	O
+on	O
+the	O
+rat	B-GENE
+GGT	I-GENE
+gene	I-GENE
+.	O
+
+A	O
+specific	O
+distal	O
+promoter	O
+controls	O
+gamma	B-GENE
+-	I-GENE
+glutamyl	I-GENE
+transpeptidase	I-GENE
+gene	I-GENE
+expression	O
+in	O
+undifferentiated	O
+rat	O
+transformed	O
+liver	O
+cells	O
+.	O
+
+These	O
+repressor	O
+sites	O
+are	O
+pyrimidine	O
+rich	O
+and	O
+bind	O
+avidly	O
+to	O
+the	O
+polypyrimidine	B-GENE
+tract	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+PTB	B-GENE
+)	O
+in	O
+HeLa	O
+nuclear	O
+extracts	O
+as	O
+determined	O
+by	O
+UV	O
+crosslinking	O
+/	O
+competition	O
+assays	O
+.	O
+
+For	O
+higher	O
+expression	O
+of	O
+lipA	B-GENE
+in	O
+S	O
+.	O
+lividans	O
+,	O
+the	O
+gene	O
+was	O
+cloned	O
+next	O
+to	O
+the	O
+strong	O
+aphII	B-GENE
+promoter	I-GENE
+.	O
+
+Within	O
+a	O
+135	O
+-	O
+bp	O
+core	O
+homology	O
+region	O
+,	O
+the	O
+human	B-GENE
+HS12	I-GENE
+enhancers	I-GENE
+are	O
+approximately	O
+90	O
+%	O
+identical	O
+to	O
+the	O
+murine	O
+homolog	O
+and	O
+include	O
+several	O
+motifs	O
+previously	O
+demonstrated	O
+to	O
+be	O
+important	O
+for	O
+function	O
+of	O
+the	O
+murine	O
+enhancer	O
+;	O
+additional	O
+segments	O
+of	O
+high	O
+sequence	O
+conservation	O
+suggest	O
+the	O
+possibility	O
+of	O
+previously	O
+unrecognized	O
+functional	O
+motifs	O
+.	O
+
+The	O
+two	O
+cysteine	O
+residues	O
+located	O
+in	O
+this	O
+additional	O
+region	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+formation	O
+of	O
+a	O
+disulfide	O
+bridge	O
+associated	O
+with	O
+the	O
+activation	O
+process	O
+of	O
+the	O
+catalytic	O
+activity	O
+.	O
+
+The	O
+por	B-GENE
+gene	I-GENE
+has	O
+been	O
+expressed	O
+,	O
+for	O
+the	O
+first	O
+time	O
+,	O
+in	O
+anaerobically	O
+grown	O
+Escherichia	O
+coli	O
+behind	O
+the	O
+isopropyl	O
+-	O
+beta	O
+-	O
+D	O
+-	O
+thiogalactopyranoside	O
+-	O
+inducible	O
+tac	B-GENE
+promoter	I-GENE
+,	O
+resulting	O
+in	O
+the	O
+production	O
+of	O
+POR	B-GENE
+in	O
+its	O
+active	O
+form	O
+.	O
+
+When	O
+the	O
+downstream	O
+operator	O
+was	O
+altered	O
+,	O
+there	O
+was	O
+a	O
+fourfold	O
+reduction	O
+in	O
+reporter	O
+enzyme	O
+levels	O
+.	O
+
+The	O
+ORF3	O
+mutant	O
+produced	O
+reduced	O
+levels	O
+of	O
+tabtoxin	B-GENE
+,	O
+indicating	O
+that	O
+ORF3	O
+may	O
+have	O
+a	O
+role	O
+in	O
+T	B-GENE
+beta	I-GENE
+L	I-GENE
+biosynthesis	O
+.	O
+
+Refined	O
+Cox	O
+models	O
+using	O
+a	O
+CD4	B-GENE
+count	O
+of	O
+150	O
+/	O
+microL	O
+rather	O
+than	O
+200	O
+/	O
+microL	O
+to	O
+distinguish	O
+I0	O
+and	O
+I1	O
+yielded	O
+a	O
+simplified	O
+model	O
+with	O
+better	O
+fit	O
+to	O
+the	O
+observed	O
+data	O
+.	O
+
+However	O
+,	O
+the	O
+published	O
+reports	O
+consist	O
+of	O
+a	O
+small	O
+number	O
+of	O
+patients	O
+and	O
+limited	O
+data	O
+.	O
+
+These	O
+transcripts	O
+contain	O
+the	O
+5	O
+'	O
+ends	O
+of	O
+mature	O
+UbCRBP	B-GENE
+mRNAs	I-GENE
+;	O
+extend	O
+through	O
+UbCRBP	B-GENE
+,	O
+across	O
+the	O
+intergenic	O
+region	O
+,	O
+and	O
+a	O
+significant	O
+distance	O
+3	O
+'	O
+into	O
+the	O
+enolase	B-GENE
+gene	I-GENE
+.	O
+
+The	O
+distribution	O
+of	O
+cryptosporidia	O
+in	O
+the	O
+intestine	O
+and	O
+number	O
+of	O
+cryptosporidia	O
+per	O
+ileal	O
+villus	O
+on	O
+different	O
+DPI	O
+were	O
+also	O
+estimated	O
+for	O
+detailed	O
+characterization	O
+of	O
+the	O
+infection	O
+in	O
+kids	O
+as	O
+a	O
+model	O
+for	O
+experimental	O
+cryptosporidiosis	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+the	O
+subendocardial	O
+/	O
+subepicardial	O
+blood	O
+flow	O
+ratio	O
+(	O
+ENDO	O
+/	O
+EPI	O
+)	O
+increased	O
+from	O
+0	O
+.	O
+44	O
++	O
+/	O
+-	O
+0	O
+.	O
+09	O
+during	O
+control	O
+stenosis	O
+to	O
+0	O
+.	O
+85	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+after	O
+ITF	O
+1129	O
+(	O
+10	O
+micrograms	O
+/	O
+kg	O
+/	O
+min	O
+i	O
+.	O
+v	O
+.	O
+)	O
+and	O
+to	O
+0	O
+.	O
+81	O
++	O
+/	O
+-	O
+0	O
+.	O
+12	O
+after	O
+NTG	O
+.	O
+
+Proteasomes	O
+are	O
+the	O
+multisubunit	O
+protease	O
+involved	O
+in	O
+the	O
+generation	O
+of	O
+peptides	O
+presented	O
+by	O
+MHC	B-GENE
+class	I-GENE
+I	I-GENE
+molecules	I-GENE
+.	O
+
+Takahashi	O
+,	O
+H	O
+.	O
+
+For	O
+sputum	B-GENE
+interleukin	I-GENE
+-	I-GENE
+8	I-GENE
+there	O
+was	O
+an	O
+estimated	O
+true	O
+treatment	O
+median	O
+difference	O
+of	O
+142	O
+pg	O
+/	O
+ml	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+(	O
+CI	O
+)	O
+8	O
+to	O
+2866	O
+pg	O
+/	O
+ml	O
+)	O
+in	O
+favour	O
+of	O
+placebo	O
+;	O
+while	O
+for	O
+maximal	O
+expiratory	O
+flow	O
+at	O
+25	O
+%	O
+(	O
+MEF25	O
+%	O
+)	O
+remaining	O
+forced	O
+vital	O
+capacity	O
+predicted	O
+for	O
+sex	O
+and	O
+height	O
+there	O
+was	O
+a	O
+15	O
+percentage	O
+points	O
+(	O
+pp	O
+)	O
+(	O
+95	O
+%	O
+CI	O
+4	O
+to	O
+26	O
+pp	O
+)	O
+mean	O
+treatment	O
+difference	O
+in	O
+favour	O
+of	O
+placebo	O
+.	O
+
+However	O
+,	O
+although	O
+deletion	O
+of	O
+Fp1	B-GENE
+in	O
+the	O
+hCRBP1	B-GENE
+gene	I-GENE
+yielded	O
+increased	O
+CAT	B-GENE
+activity	O
+,	O
+pointing	O
+toward	O
+a	O
+negative	O
+regulatory	O
+function	O
+exerted	O
+by	O
+this	O
+element	O
+,	O
+its	O
+insertion	O
+upstream	O
+of	O
+the	O
+p12	B-GENE
+basal	I-GENE
+promoter	I-GENE
+results	O
+in	O
+an	O
+impressive	O
+positive	O
+stimulation	O
+of	O
+CAT	B-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Gaucher	O
+'	O
+s	O
+disease	O
+is	O
+a	O
+rare	O
+metabolic	O
+disorder	O
+characterized	O
+by	O
+the	O
+lack	O
+of	O
+beta	B-GENE
+-	I-GENE
+glucocerebrosidase	I-GENE
+enzyme	I-GENE
+.	O
+
+The	O
+9	O
+;	O
+22	O
+chromosomal	O
+translocation	O
+characteristic	O
+of	O
+CML	O
+results	O
+in	O
+a	O
+fused	O
+bcr	B-GENE
+/	O
+abl	B-GENE
+gene	O
+and	O
+an	O
+abnormal	O
+fusion	O
+protein	O
+,	O
+p210bcr	B-GENE
+/	O
+abl	B-GENE
+.	O
+
+By	O
+analyzing	O
+the	O
+RanGAP	B-GENE
+activity	O
+of	O
+a	O
+series	O
+of	O
+recombinantly	O
+expressed	O
+rna1p	B-GENE
+mutant	I-GENE
+derivatives	O
+,	O
+we	O
+show	O
+that	O
+the	O
+highly	O
+acidic	O
+sequence	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+domain	O
+of	O
+both	O
+yeast	O
+proteins	O
+is	O
+indispensable	O
+for	O
+activating	O
+Ran	B-GENE
+-	O
+mediated	O
+GTP	O
+hydrolysis	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+MHC	B-GENE
+class	I-GENE
+II	I-GENE
+,	O
+purified	B-GENE
+soluble	I-GENE
+D10	I-GENE
+TCR	I-GENE
+bound	O
+to	O
+Staphylococcus	B-GENE
+aureus	I-GENE
+enterotoxin	I-GENE
+C2	I-GENE
+with	O
+an	O
+association	O
+rate	O
+of	O
+1	O
+.	O
+69	O
++	O
+/	O
+-	O
+0	O
+.	O
+12	O
+x	O
+10	O
+(	O
+4	O
+)	O
+M	O
+(	O
+-	O
+1	O
+)	O
+sec	O
+(	O
+-	O
+1	O
+)	O
+and	O
+a	O
+dissociation	O
+rate	O
+of	O
+1	O
+.	O
+9	O
++	O
+/	O
+-	O
+0	O
+.	O
+47	O
+x	O
+10	O
+(	O
+-	O
+2	O
+)	O
+sec	O
+(	O
+-	O
+1	O
+)	O
+,	O
+giving	O
+a	O
+dissociation	O
+constant	O
+of	O
+1	O
+.	O
+1	O
+microM	O
+.	O
+
+Evidence	O
+for	O
+such	O
+peak	O
+shifts	O
+has	O
+been	O
+found	O
+in	O
+the	O
+responses	O
+of	O
+auditory	O
+nerve	O
+fibers	O
+,	O
+cochlear	O
+microphonics	O
+,	O
+and	O
+the	O
+responses	O
+of	O
+outer	O
+hair	O
+cells	O
+and	O
+supporting	O
+cells	O
+in	O
+the	O
+cochlea	O
+,	O
+as	O
+well	O
+as	O
+in	O
+basilar	O
+membrane	O
+vibration	O
+measurements	O
+,	O
+and	O
+indirectly	O
+,	O
+in	O
+psychophysical	O
+data	O
+.	O
+
+Mnt	B-GENE
+:	O
+Max	B-GENE
+complexes	O
+also	O
+efficiently	O
+suppress	O
+Myc	B-GENE
+-	O
+dependent	O
+activation	O
+from	O
+the	O
+same	O
+promoter	O
+.	O
+
+Assays	O
+of	O
+total	O
+cholesterol	O
+as	O
+well	O
+as	O
+the	O
+HDL	B-GENE
+,	O
+HDL2	B-GENE
+,	O
+LDL	B-GENE
+,	O
+triglycerides	O
+,	O
+endothelin	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+lipoprotein	B-GENE
+(	I-GENE
+a	I-GENE
+)	I-GENE
+,	O
+estradiol	O
+and	O
+FSH	B-GENE
+were	O
+also	O
+obtained	O
+at	O
+baseline	O
+before	O
+receiving	O
+ERT	O
+and	O
+after	O
+3	O
+months	O
+of	O
+ERT	O
+.	O
+
+Six	O
+tandem	O
+repeats	O
+of	O
+the	O
+P	B-GENE
+element	I-GENE
+linked	O
+to	O
+the	O
+SV40	B-GENE
+promoter	I-GENE
+responded	O
+to	O
+phorbol	O
+12	O
+-	O
+myristate	O
+13	O
+-	O
+acetate	O
+,	O
+while	O
+that	O
+of	O
+other	O
+elements	O
+did	O
+not	O
+.	O
+
+The	O
+distributed	O
+current	O
+density	O
+J	O
+is	O
+calculated	O
+within	O
+the	O
+volume	O
+defined	O
+by	O
+the	O
+motor	O
+unit	O
+.	O
+
+The	O
+cleavage	O
+dipeptides	O
+of	O
+C1YVV	B-GENE
+NIa	I-GENE
+protease	I-GENE
+are	O
+Q	O
+(	O
+E	O
+)	O
+/	O
+S	O
+(	O
+A	O
+,	O
+G	O
+)	O
+.	O
+
+However	O
+,	O
+we	O
+were	O
+unable	O
+to	O
+identify	O
+a	O
+p4	B-GENE
+molecule	O
+.	O
+
+(	O
+iv	O
+)	O
+The	O
+accumulation	O
+of	O
+cyclin	B-GENE
+D3	I-GENE
+protein	I-GENE
+in	O
+Vero	O
+cells	O
+infected	O
+with	O
+an	O
+alpha0	B-GENE
+deletion	I-GENE
+mutant	I-GENE
+was	O
+reduced	O
+relative	O
+to	O
+that	O
+of	O
+cells	O
+infected	O
+with	O
+wild	O
+-	O
+type	O
+virus	O
+or	O
+a	O
+recombinant	O
+virus	O
+in	O
+which	O
+the	O
+deleted	O
+alpha0	B-GENE
+sequences	I-GENE
+were	O
+restored	O
+.	O
+
+We	O
+report	O
+the	O
+preliminary	O
+biochemical	O
+characterization	O
+of	O
+the	O
+T	B-GENE
+antigens	I-GENE
+encoded	O
+by	O
+three	O
+SV40	O
+mutants	O
+,	O
+5030	O
+,	O
+5031	O
+,	O
+and	O
+5061	O
+,	O
+each	O
+of	O
+which	O
+have	O
+altered	O
+residues	O
+within	O
+or	O
+near	O
+the	O
+ATP	O
+binding	O
+pocket	O
+.	O
+
+These	O
+effects	O
+were	O
+abrogated	O
+by	O
+co	O
+-	O
+expression	O
+of	O
+kinase	B-GENE
+-	I-GENE
+deficient	I-GENE
+PKC	I-GENE
+zeta	I-GENE
+and	O
+inhibition	O
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+p85alpha	B-GENE
+-	O
+p110	B-GENE
+by	O
+wortmannin	O
+,	O
+LY294002	O
+and	O
+a	O
+dominant	O
+-	O
+negative	O
+mutant	O
+of	O
+p85alpha	B-GENE
+.	O
+
+Protein	B-GENE
+phosphatase	I-GENE
+2A	I-GENE
+is	O
+a	O
+critical	O
+regulator	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+zeta	I-GENE
+signaling	O
+targeted	O
+by	O
+SV40	B-GENE
+small	I-GENE
+t	I-GENE
+to	O
+promote	O
+cell	O
+growth	O
+and	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activation	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+RXRalphaF318A	B-GENE
+constitutive	O
+activity	O
+generated	O
+within	O
+heterodimers	O
+in	O
+the	O
+presence	O
+of	O
+BMS614	O
+requires	O
+the	O
+integrity	O
+of	O
+both	O
+RXR	B-GENE
+and	O
+RAR	B-GENE
+AF	O
+-	O
+2	O
+domains	O
+.	O
+
+These	O
+introns	O
+contain	O
+only	O
+single	O
+snoRNA	B-GENE
+genes	I-GENE
+and	O
+their	O
+processing	O
+involves	O
+exonucleolytic	O
+release	O
+of	O
+the	O
+snoRNA	O
+from	O
+debranched	O
+intron	O
+lariats	O
+.	O
+
+Recent	O
+studies	O
+have	O
+shown	O
+that	O
+the	O
+Src	B-GENE
+homology	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+SH2	B-GENE
+)	O
+domain	O
+-	O
+containing	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+,	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+associates	O
+with	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+PECAM	B-GENE
+-	I-GENE
+1	I-GENE
+as	O
+it	O
+becomes	O
+tyrosine	O
+-	O
+phosphorylated	O
+during	O
+platelet	O
+aggregation	O
+:	O
+a	O
+process	O
+that	O
+can	O
+be	O
+mimicked	O
+in	O
+part	O
+by	O
+small	O
+synthetic	O
+phosphopeptides	O
+corresponding	O
+to	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+PECAM	B-GENE
+-	I-GENE
+1	I-GENE
+encompassing	O
+tyrosine	O
+residues	O
+Tyr	O
+-	O
+663	O
+or	O
+Tyr	O
+-	O
+686	O
+.	O
+
+Underlying	O
+the	O
+clustering	O
+of	O
+these	O
+risk	O
+variables	O
+were	O
+three	O
+factors	O
+.	O
+
+Supplementation	O
+was	O
+stopped	O
+when	O
+pl	B-GENE
+-	I-GENE
+ALB	I-GENE
+reached	O
+2	O
+.	O
+0	O
+g	O
+/	O
+dL	O
+.	O
+
+Detection	O
+of	O
+airborne	O
+Mycobacterium	O
+tuberculosis	O
+by	O
+air	O
+filtration	O
+and	O
+polymerase	O
+chain	O
+reaction	O
+.	O
+
+These	O
+findings	O
+show	O
+that	O
+EBP50	B-GENE
+is	O
+a	O
+physiologically	O
+relevant	O
+ezrin	B-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+This	O
+family	O
+of	O
+proteins	O
+binds	O
+GC	O
+-	O
+rich	O
+motifs	O
+widely	O
+distributed	O
+in	O
+gene	O
+promoters	O
+,	O
+resulting	O
+in	O
+distinct	O
+activation	O
+or	O
+repression	O
+of	O
+transcriptional	O
+activities	O
+.	O
+
+Deletion	O
+of	O
+the	O
+POR2	B-GENE
+gene	I-GENE
+alone	O
+had	O
+no	O
+detectable	O
+phenotype	O
+,	O
+while	O
+yeasts	O
+with	O
+deletions	O
+of	O
+both	O
+the	O
+POR1	B-GENE
+and	O
+POR2	B-GENE
+genes	I-GENE
+were	O
+viable	O
+and	O
+able	O
+to	O
+grow	O
+on	O
+glycerol	O
+at	O
+30	O
+degrees	O
+C	O
+,	O
+albeit	O
+more	O
+slowly	O
+than	O
+delta	B-GENE
+por1	I-GENE
+single	I-GENE
+mutants	I-GENE
+.	O
+
+Furthermore	O
+,	O
+our	O
+novel	O
+observation	O
+that	O
+expression	O
+of	O
+a	O
+highly	O
+activated	O
+FGFR3	B-GENE
+kinase	I-GENE
+domain	I-GENE
+is	O
+able	O
+to	O
+morphologically	O
+transform	O
+fibroblasts	O
+suggests	O
+that	O
+dysregulation	O
+of	O
+FGFR3	B-GENE
+has	O
+the	O
+potential	O
+to	O
+play	O
+a	O
+role	O
+in	O
+human	O
+neoplasia	O
+.	O
+
+Involvement	O
+of	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+in	O
+regulation	O
+of	O
+the	O
+R	B-GENE
+-	I-GENE
+FABP	I-GENE
+gene	I-GENE
+in	O
+the	O
+developing	O
+chick	O
+retina	O
+.	O
+
+However	O
+,	O
+Cbf5p	B-GENE
+was	O
+found	O
+to	O
+be	O
+nucleolar	O
+and	O
+is	O
+highly	O
+homologous	O
+to	O
+the	O
+rat	B-GENE
+nucleolar	I-GENE
+protein	I-GENE
+NAP57	I-GENE
+,	O
+which	O
+coimmunoprecipitates	O
+with	O
+Nopp140	B-GENE
+and	O
+which	O
+is	O
+postulated	O
+to	O
+be	O
+involved	O
+in	O
+nucleolar	O
+-	O
+cytoplasmic	O
+shuttling	O
+(	O
+U	O
+.	O
+
+This	O
+newly	O
+described	O
+organism	O
+was	O
+difficult	O
+to	O
+identify	O
+due	O
+to	O
+discrepancies	O
+between	O
+the	O
+Vitek	O
+and	O
+API	O
+20E	O
+identification	O
+systems	O
+.	O
+
+Ig	B-GENE
+heavy	I-GENE
+chain	I-GENE
+class	O
+switching	O
+is	O
+directed	O
+by	O
+cytokines	O
+inducing	O
+transcription	O
+from	O
+unrearranged	O
+CH	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+available	O
+data	O
+suggest	O
+that	O
+the	O
+NF	B-GENE
+kappa	I-GENE
+B2	I-GENE
+nucleoprotein	I-GENE
+complex	I-GENE
+may	O
+cooperate	O
+with	O
+DNA	O
+-	O
+bound	O
+STAT6	B-GENE
+to	O
+achieve	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+-	O
+dependent	O
+activation	O
+of	O
+the	O
+human	B-GENE
+IgE	I-GENE
+germline	I-GENE
+gene	I-GENE
+.	O
+
+EXERCISE	O
+IN	O
+THE	O
+TERRESTRIAL	O
+CHRISTMAS	O
+ISLAND	O
+RED	O
+CRAB	O
+GECARCOIDEA	O
+NATALIS	O
+-	O
+ENERGETICS	O
+OF	O
+LOCOMOTION	O
+
+THE	O
+SCALING	O
+OF	O
+SONG	O
+FREQUENCY	O
+IN	O
+CICADAS	O
+
+In	O
+this	O
+study	O
+we	O
+have	O
+introduced	O
+mutations	O
+into	O
+the	O
+corresponding	O
+elements	O
+of	O
+two	O
+cox3	B-GENE
+promoters	I-GENE
+and	O
+show	O
+that	O
+while	O
+the	O
+core	O
+element	O
+is	O
+essential	O
+for	O
+cox3	B-GENE
+promoter	I-GENE
+activity	O
+,	O
+upstream	O
+element	O
+mutations	O
+have	O
+little	O
+or	O
+no	O
+effect	O
+.	O
+
+We	O
+found	O
+that	O
+multiple	O
+tumor	O
+suppressor	O
+genes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+p53	B-GENE
+,	O
+DCC	B-GENE
+,	O
+APC	B-GENE
+,	O
+MCC	B-GENE
+,	O
+BRCA1	B-GENE
+,	O
+and	O
+WAF1	B-GENE
+/	O
+CIP1	B-GENE
+)	O
+were	O
+inactivated	O
+at	O
+different	O
+frequencies	O
+via	O
+various	O
+mechanisms	O
+[	O
+e	O
+.	O
+g	O
+.	O
+,	O
+loss	O
+of	O
+heterozygosity	O
+(	O
+LOH	O
+)	O
+,	O
+loss	O
+of	O
+expression	O
+(	O
+LOE	O
+)	O
+,	O
+mutation	O
+,	O
+and	O
+inactivation	O
+by	O
+cellular	O
+binding	O
+protein	O
+]	O
+.	O
+
+The	O
+histidine	O
+-	O
+tagged	O
+gene	O
+,	O
+rpoCHIS	B-GENE
+,	O
+was	O
+used	O
+to	O
+replace	O
+the	O
+wild	O
+-	O
+type	O
+allele	O
+in	O
+the	O
+chromosome	O
+of	O
+S	O
+.	O
+coelicolor	O
+and	O
+S	O
+.	O
+lividans	O
+.	O
+
+Because	O
+the	O
+deletion	O
+included	O
+the	O
+TK	B-GENE
+gene	I-GENE
+,	O
+selection	O
+with	O
+gancyclovir	O
+against	O
+cells	O
+not	O
+having	O
+undergone	O
+recombination	O
+was	O
+possible	O
+.	O
+
+Lack	O
+of	O
+controlled	O
+prospective	O
+studies	O
+of	O
+sleep	O
+electroencephalograms	O
+(	O
+EEG	O
+)	O
+,	O
+and	O
+the	O
+use	O
+of	O
+medication	O
+,	O
+in	O
+children	O
+with	O
+developmental	O
+dysphasia	O
+,	O
+may	O
+deny	O
+appropriate	O
+treatment	O
+strategies	O
+to	O
+children	O
+with	O
+severe	O
+developmental	O
+speech	O
+and	O
+language	O
+disorders	O
+.	O
+
+Widening	O
+of	O
+the	O
+abdominal	O
+aortic	O
+wall	O
+on	O
+an	O
+ultrasound	O
+examination	O
+was	O
+the	O
+key	O
+to	O
+the	O
+incidental	O
+diagnosis	O
+of	O
+a	O
+clinically	O
+unsuspected	O
+type	O
+B	O
+dissection	O
+.	O
+
+Fermentation	O
+process	O
+after	O
+supplementation	O
+of	O
+nitrate	O
+,	O
+nitrite	O
+,	O
+lactic	O
+acid	O
+bacteria	O
+and	O
+formic	O
+acid	O
+
+Substrates	O
+include	O
+the	O
+p21	B-GENE
+(	O
+ras	B-GENE
+)	O
+proteins	O
+,	O
+nuclear	B-GENE
+lamins	I-GENE
+,	O
+and	O
+a	O
+series	O
+of	O
+retinal	O
+proteins	O
+.	O
+
+Ovaries	O
+of	O
+10	O
+animals	O
+per	O
+group	O
+from	O
+16	O
+studies	O
+in	O
+CD	O
+-	O
+1	O
+mice	O
+and	O
+1	O
+study	O
+each	O
+in	O
+C3H	O
+and	O
+C57BL	O
+/	O
+6	O
+mice	O
+were	O
+sectioned	O
+serially	O
+at	O
+6	O
+microm	O
+.	O
+
+The	O
+Trx	B-GENE
+-	O
+CT	B-GENE
+fusion	O
+protein	O
+was	O
+produced	O
+less	O
+efficiently	O
+(	O
+20	O
+%	O
+of	O
+total	O
+soluble	O
+cellular	O
+protein	O
+)	O
+.	O
+
+A	O
+data	O
+base	O
+homology	O
+search	O
+revealed	O
+that	O
+the	O
+predicted	O
+ER1	B-GENE
+amino	O
+acid	O
+sequence	O
+contains	O
+three	O
+regions	O
+of	O
+similarity	O
+to	O
+the	O
+rat	O
+and	O
+human	O
+proteins	O
+encoded	O
+by	O
+the	O
+metastasis	O
+-	O
+associated	O
+gene	O
+,	O
+mta1	B-GENE
+,	O
+and	O
+two	O
+regions	O
+of	O
+similarity	O
+to	O
+the	O
+Caenorhabditis	O
+elegans	O
+sequence	O
+that	O
+is	O
+similar	O
+to	O
+mta1	B-GENE
+.	O
+
+The	O
+sequenced	O
+cDNA	O
+predicts	O
+a	O
+704	O
+-	O
+amino	O
+acid	O
+protein	O
+80	O
+%	O
+identical	O
+to	O
+human	B-GENE
+progelatinase	I-GENE
+B	I-GENE
+.	O
+
+The	O
+inhibition	O
+by	O
+cytosolic	O
+Ca2	O
++	O
+was	O
+caused	O
+by	O
+a	O
+decrease	O
+in	O
+cooperativity	O
+and	O
+by	O
+a	O
+shift	O
+in	O
+EC50	O
+toward	O
+higher	O
+InsP3	O
+concentrations	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+standardised	O
+mortality	O
+ratio	O
+(	O
+SMR	O
+)	O
+for	O
+all	O
+malignant	O
+neoplasms	O
+was	O
+94	O
+(	O
+95	O
+%	O
+CI	O
+74	O
+to	O
+118	O
+)	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+this	O
+region	O
+revealed	O
+three	O
+eight	O
+-	O
+bp	O
+repetitive	O
+elements	O
+,	O
+the	O
+deletion	O
+of	O
+which	O
+restored	O
+wild	O
+-	O
+type	O
+levels	O
+of	O
+luciferase	B-GENE
+activity	O
+to	O
+the	O
+-	O
+916	O
+-	O
+bp	O
+reporter	O
+plasmid	O
+.	O
+
+Using	O
+5	O
+'	O
+RACE	O
+and	O
+reverse	O
+transcription	O
+-	O
+PCR	O
+(	O
+RT	O
+-	O
+PCR	O
+)	O
+methodologies	O
+,	O
+we	O
+cloned	O
+these	O
+sequences	O
+from	O
+brain	O
+and	O
+placenta	O
+and	O
+found	O
+this	O
+material	O
+to	O
+be	O
+composed	O
+of	O
+alternatively	O
+spliced	O
+exons	O
+using	O
+a	O
+previously	O
+reported	O
+noncoding	O
+exon	O
+(	O
+1A	O
+)	O
+and	O
+a	O
+novel	O
+97	O
+-	O
+bp	O
+noncoding	O
+exon	O
+(	O
+1B	O
+)	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+study	O
+in	O
+which	O
+mutation	O
+screening	O
+has	O
+been	O
+performed	O
+for	O
+both	O
+the	O
+EXT1	B-GENE
+and	O
+EXT2	B-GENE
+genes	I-GENE
+prior	O
+to	O
+any	O
+linkage	O
+analysis	O
+.	O
+
+Positron	O
+emission	O
+tomography	O
+radioligands	O
+for	O
+dopamine	B-GENE
+transporters	I-GENE
+and	O
+studies	O
+in	O
+human	O
+and	O
+nonhuman	O
+primates	O
+.	O
+
+Expression	O
+from	O
+this	O
+element	O
+is	O
+regulated	O
+by	O
+a	O
+heteromeric	O
+protein	O
+complex	O
+containing	O
+ubiquitous	O
+(	O
+i	O
+.	O
+e	O
+.	O
+the	O
+E2A	B-GENE
+-	O
+and	O
+HEB	B-GENE
+-	I-GENE
+encoded	I-GENE
+proteins	I-GENE
+)	O
+and	O
+islet	O
+-	O
+enriched	O
+members	O
+of	O
+the	O
+bHLH	B-GENE
+family	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+CCAAT	O
+box	O
+also	O
+has	O
+tissue	O
+-	O
+specific	O
+characteristics	O
+that	O
+assist	O
+in	O
+targeting	O
+expression	O
+of	O
+the	O
+alpha	B-GENE
+-	I-GENE
+subunit	I-GENE
+gene	I-GENE
+to	O
+trophoblasts	O
+.	O
+
+U4	B-GENE
+/	O
+U6	B-GENE
+snRNP	O
+is	O
+one	O
+of	O
+four	O
+essential	O
+small	O
+nuclear	O
+ribonucleoprotein	O
+(	O
+snRNP	O
+)	O
+particles	O
+(	O
+U1	B-GENE
+,	O
+U2	B-GENE
+,	O
+U5	B-GENE
+and	O
+U4	B-GENE
+/	O
+U6	B-GENE
+)	O
+present	O
+in	O
+the	O
+spliceosome	O
+.	O
+
+Hprp3p	B-GENE
+is	O
+a	O
+77	O
+kDa	O
+protein	O
+,	O
+which	O
+is	O
+homologous	O
+to	O
+the	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+splicing	I-GENE
+factor	I-GENE
+Prp3p	I-GENE
+.	O
+
+The	O
+growth	O
+-	O
+promoting	O
+properties	O
+of	O
+the	O
+retroviral	B-GENE
+v	I-GENE
+-	I-GENE
+erbA	I-GENE
+oncogene	I-GENE
+,	O
+a	O
+highly	O
+mutated	O
+version	O
+of	O
+the	O
+chicken	B-GENE
+thyroid	I-GENE
+hormone	I-GENE
+receptor	I-GENE
+(	I-GENE
+TR	I-GENE
+)	I-GENE
+alpha	I-GENE
+,	O
+have	O
+so	O
+far	O
+exclusively	O
+been	O
+linked	O
+to	O
+dominant	O
+repression	O
+of	O
+the	O
+antimitogenic	O
+roles	O
+of	O
+TR	B-GENE
+and	O
+retinoic	B-GENE
+acid	I-GENE
+receptors	I-GENE
+.	O
+
+We	O
+cloned	O
+a	O
+complete	O
+cDNA	O
+(	O
+2	O
+.	O
+9	O
+kb	O
+)	O
+for	O
+HET	B-GENE
+from	O
+an	O
+MCF	O
+-	O
+7	O
+cDNA	O
+library	O
+.	O
+
+The	O
+most	O
+common	O
+grade	O
+3	O
+toxicity	O
+was	O
+neutropenia	O
+,	O
+thrombocytopenia	O
+,	O
+and	O
+parasthesias	O
+(	O
+observed	O
+in	O
+<	O
+10	O
+%	O
+of	O
+cycles	O
+)	O
+.	O
+
+Serum	O
+concentrations	O
+of	O
+E2	O
+and	O
+TBOH	O
+were	O
+measured	O
+on	O
+d	O
+0	O
+,	O
+1	O
+,	O
+3	O
+,	O
+5	O
+,	O
+7	O
+,	O
+13	O
+,	O
+21	O
+,	O
+28	O
+,	O
+42	O
+,	O
+56	O
+,	O
+84	O
+,	O
+112	O
+,	O
+and	O
+140	O
+in	O
+finishing	O
+heifers	O
+administered	O
+the	O
+following	O
+treatments	O
+:	O
+1	O
+)	O
+control	O
+;	O
+2	O
+)	O
+MGA	O
+,	O
+.	O
+5	O
+mg	O
+per	O
+heifer	O
+daily	O
+;	O
+3	O
+)	O
+Revalor	O
+-	O
+H	O
+(	O
+140	O
+mg	O
+TBA	O
++	O
+14	O
+mg	O
+E2	O
+)	O
+;	O
+4	O
+)	O
+Revalor	O
+-	O
+H	O
++	O
+MGA	O
+;	O
+5	O
+)	O
+Finaplix	O
+-	O
+H	O
+(	O
+200	O
+mg	O
+TBA	O
+)	O
+;	O
+and	O
+6	O
+)	O
+Finaplix	O
+-	O
+H	O
++	O
+MGA	O
+.	O
+
+Serum	O
+E2	O
+concentrations	O
+increased	O
+numerically	O
+two	O
+-	O
+to	O
+threefold	O
+from	O
+d	O
+56	O
+to	O
+140	O
+in	O
+controls	O
+fed	O
+MGA	O
+,	O
+compared	O
+with	O
+controls	O
+not	O
+fed	O
+MGA	O
+.	O
+
+Interferon	B-GENE
+Regulatory	I-GENE
+Factor	I-GENE
+(	I-GENE
+IRF	I-GENE
+)	I-GENE
+-	I-GENE
+1	I-GENE
+has	O
+been	O
+characterized	O
+as	O
+an	O
+important	O
+growth	O
+regulatory	O
+and	O
+immunomodulatory	O
+transcription	O
+factor	O
+.	O
+
+The	O
+genomic	O
+structure	O
+of	O
+brk	B-GENE
+consists	O
+of	O
+8	O
+exons	O
+,	O
+whose	O
+boundaries	O
+are	O
+distinct	O
+from	O
+other	O
+non	O
+-	O
+receptor	O
+PTK	B-GENE
+family	I-GENE
+members	O
+,	O
+again	O
+indicating	O
+a	O
+structural	O
+and	O
+functional	O
+divergence	O
+.	O
+
+We	O
+have	O
+previously	O
+reported	O
+that	O
+expression	O
+of	O
+a	O
+tumour	O
+derived	O
+brk	B-GENE
+cDNA	I-GENE
+in	O
+mouse	O
+embryonic	O
+fibroblasts	O
+and	O
+human	O
+mammary	O
+epithelial	O
+cells	O
+supports	O
+anchorage	O
+independent	O
+growth	O
+,	O
+and	O
+in	O
+the	O
+latter	O
+potentiates	O
+the	O
+mitogenic	O
+response	O
+to	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+.	O
+
+Anti	B-GENE
+-	I-GENE
+hepatitis	I-GENE
+A	I-GENE
+virus	O
+(	O
+HAV	O
+)	O
+titer	O
+after	O
+vaccination	O
+was	O
+measured	O
+in	O
+83	O
+HIV	O
+-	O
+positive	O
+and	O
+39	O
+HIV	O
+-	O
+negative	O
+men	O
+.	O
+
+One	O
+skull	O
+does	O
+not	O
+a	O
+species	O
+make	O
+.	O
+
+Surprisingly	O
+,	O
+calf	B-GENE
+thymus	I-GENE
+CstF	I-GENE
+contained	O
+an	O
+additional	O
+,	O
+novel	O
+form	O
+of	O
+the	O
+64	O
+-	O
+kDa	O
+subunit	O
+with	O
+a	O
+molecular	O
+mass	O
+of	O
+70	O
+kDa	O
+.	O
+
+Our	O
+results	O
+favor	O
+the	O
+possibility	O
+that	O
+the	O
+Drosophila	B-GENE
+EGF	I-GENE
+receptor	I-GENE
+DER	B-GENE
+/	O
+Egfr	B-GENE
+expressed	O
+by	O
+the	O
+EMA	O
+cells	O
+functions	O
+as	O
+a	O
+receptor	O
+for	O
+Vein	B-GENE
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+In	O
+807	O
+consecutive	O
+patients	O
+from	O
+the	O
+Chilean	O
+National	O
+Registry	O
+of	O
+Acute	O
+Myocardial	O
+Infarction	O
+we	O
+analyzed	O
+the	O
+resolution	O
+of	O
+chest	O
+pain	O
+and	O
+ST	O
+segment	O
+elevation	O
+over	O
+50	O
+%	O
+within	O
+the	O
+first	O
+90	O
+min	O
+,	O
+abrupt	O
+CK	B-GENE
+rise	O
+within	O
+8	O
+h	O
+and	O
+T	O
+wave	O
+inversion	O
+in	O
+infarct	O
+related	O
+EKG	O
+leads	O
+within	O
+the	O
+first	O
+24	O
+h	O
+after	O
+thrombolysis	O
+.	O
+
+Because	O
+of	O
+the	O
+operon	O
+structure	O
+of	O
+this	O
+organism	O
+,	O
+traditional	O
+methods	O
+such	O
+as	O
+insertional	O
+mutagenesis	O
+run	O
+the	O
+risk	O
+of	O
+introducing	O
+polar	O
+effects	O
+on	O
+downstream	O
+genes	O
+or	O
+creating	O
+secondary	O
+mutations	O
+elsewhere	O
+in	O
+the	O
+genome	O
+.	O
+
+It	O
+has	O
+been	O
+proposed	O
+that	O
+the	O
+parCBA	B-GENE
+operon	I-GENE
+encodes	O
+a	O
+plasmid	O
+partitioning	O
+system	O
+(	O
+M	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+insertion	O
+of	O
+the	O
+ColE1	B-GENE
+cer	I-GENE
+site	I-GENE
+into	O
+the	O
+RK2	O
+plasmid	O
+deleted	O
+for	O
+the	O
+par	O
+region	O
+failed	O
+to	O
+stabilize	O
+the	O
+plasmid	O
+in	O
+the	O
+MC1061K	O
+strain	O
+,	O
+indicating	O
+that	O
+the	O
+multimer	O
+resolution	O
+activity	O
+encoded	O
+by	O
+parCBA	B-GENE
+is	O
+not	O
+by	O
+itself	O
+responsible	O
+for	O
+the	O
+stabilization	O
+activity	O
+observed	O
+for	O
+this	O
+operon	O
+.	O
+
+To	O
+examine	O
+the	O
+basis	O
+for	O
+the	O
+apparent	O
+differences	O
+in	O
+postsegregational	O
+killing	O
+between	O
+the	O
+two	O
+E	O
+.	O
+coli	O
+strains	O
+,	O
+transformation	O
+assays	O
+were	O
+carried	O
+out	O
+to	O
+determine	O
+the	O
+relative	O
+sensitivities	O
+of	O
+the	O
+strains	O
+to	O
+the	O
+ParE	B-GENE
+toxin	I-GENE
+protein	I-GENE
+.	O
+
+Splice	O
+-	O
+junction	O
+elements	O
+and	O
+intronic	O
+sequences	O
+regulate	O
+alternative	O
+splicing	O
+of	O
+the	O
+Drosophila	O
+myosin	B-GENE
+heavy	I-GENE
+chain	I-GENE
+gene	I-GENE
+transcript	O
+.	O
+
+Nucleotide	O
+sequence	O
+analysis	O
+of	O
+R	O
+has	O
+revealed	O
+similarities	O
+to	O
+the	O
+R1	O
+plasmid	O
+found	O
+in	O
+some	O
+South	O
+American	O
+maize	O
+races	O
+with	O
+RU	O
+cytoplasm	O
+,	O
+to	O
+the	O
+M1	O
+plasmid	O
+found	O
+in	O
+one	O
+source	O
+of	O
+Zea	O
+luxurians	O
+teosinte	O
+,	O
+to	O
+the	O
+atp9	B-GENE
+mitochondrial	I-GENE
+gene	I-GENE
+and	O
+its	O
+3	O
+'	O
+flanking	O
+sequence	O
+,	O
+and	O
+also	O
+to	O
+a	O
+region	O
+3	O
+'	O
+to	O
+the	O
+orf221	B-GENE
+gene	I-GENE
+.	O
+
+We	O
+have	O
+measured	O
+the	O
+kinetics	O
+of	O
+the	O
+recovery	O
+of	O
+mRNA	O
+synthesis	O
+in	O
+the	O
+inducible	O
+GAL10	B-GENE
+and	O
+RNR3	B-GENE
+genes	I-GENE
+after	O
+exposure	O
+of	O
+yeast	O
+cells	O
+to	O
+ultraviolet	O
+(	O
+UV	O
+)	O
+radiation	O
+.	O
+
+Cloning	O
+of	O
+a	O
+human	B-GENE
+phosphoinositide	I-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+with	O
+a	O
+C2	B-GENE
+domain	O
+that	O
+displays	O
+reduced	O
+sensitivity	O
+to	O
+the	O
+inhibitor	O
+wortmannin	O
+.	O
+
+Ea	O
+value	O
+was	O
+calculated	O
+as	O
+the	O
+ratio	O
+of	O
+the	O
+steady	O
+-	O
+state	O
+end	O
+-	O
+systolic	O
+aortic	O
+pressure	O
+(	O
+ESAP	O
+)	O
+to	O
+stroke	O
+volume	O
+(	O
+thermodilution	O
+)	O
+.	O
+
+Functional	O
+analysis	O
+of	O
+promoter	O
+activity	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+cyclin	B-GENE
+D2	I-GENE
+suggested	O
+that	O
+the	O
+region	O
+-	O
+1	O
+,	O
+100	O
+to	O
+-	O
+805	O
+including	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+,	O
+PEA3	B-GENE
+,	O
+AP2	B-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+,	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+,	O
+and	O
+Sp1	B-GENE
+may	O
+have	O
+a	O
+major	O
+positive	O
+regulatory	O
+activity	O
+for	O
+expression	O
+of	O
+cyclin	B-GENE
+D2	I-GENE
+.	O
+
+Effect	O
+of	O
+alcohol	O
+on	O
+minimal	O
+effective	O
+nCPAP	O
+pressure	O
+
+In	O
+contrast	O
+,	O
+resensitization	O
+of	O
+a	O
+sequestration	O
+-	O
+impaired	O
+beta2AR	B-GENE
+mutant	O
+(	O
+Y326A	O
+)	O
+was	O
+reestablished	O
+following	O
+the	O
+overexpression	O
+of	O
+either	O
+GRK2	B-GENE
+or	O
+beta	B-GENE
+-	I-GENE
+arrestin	I-GENE
+1	I-GENE
+.	O
+
+The	O
+medium	O
+chains	O
+of	O
+these	O
+complexes	O
+,	O
+mu1	B-GENE
+and	O
+mu2	B-GENE
+,	O
+have	O
+been	O
+implicated	O
+in	O
+two	O
+types	O
+of	O
+interaction	O
+:	O
+assembly	O
+with	O
+the	O
+beta1	B-GENE
+and	I-GENE
+beta2	I-GENE
+chains	I-GENE
+of	O
+the	O
+corresponding	O
+complexes	O
+and	O
+recognition	O
+of	O
+tyrosine	O
+-	O
+based	O
+sorting	O
+signals	O
+.	O
+
+Osmotic	O
+shock	O
+stimulates	O
+GLUT4	B-GENE
+translocation	O
+in	O
+3T3L1	O
+adipocytes	O
+by	O
+a	O
+novel	O
+tyrosine	B-GENE
+kinase	I-GENE
+pathway	O
+.	O
+
+We	O
+also	O
+identified	O
+Sp1	B-GENE
+,	O
+Sp3	B-GENE
+,	O
+and	O
+NGFI	B-GENE
+-	I-GENE
+A	I-GENE
+/	O
+Egr	B-GENE
+-	I-GENE
+1	I-GENE
+as	O
+the	O
+primary	O
+nuclear	O
+transcription	O
+factors	O
+binding	O
+to	O
+TRE1	B-GENE
+which	O
+mediate	O
+Tax	B-GENE
+responsiveness	O
+.	O
+
+Interestingly	O
+,	O
+segment	O
+nesting	O
+differentially	O
+increases	O
+the	O
+copy	O
+number	O
+of	O
+genes	O
+encoded	O
+by	O
+segment	O
+W	O
+,	O
+suggesting	O
+that	O
+the	O
+unusual	O
+genomic	O
+organization	O
+of	O
+PDVs	O
+may	O
+be	O
+directly	O
+linked	O
+to	O
+the	O
+unique	O
+functions	O
+of	O
+this	O
+virus	O
+in	O
+its	O
+obligate	O
+mutualistic	O
+association	O
+with	O
+parasitic	O
+wasps	O
+.	O
+
+Processivity	O
+of	O
+DNA	O
+synthesis	O
+by	O
+the	O
+mutant	O
+holoenzyme	O
+containing	O
+pcna	B-GENE
+-	I-GENE
+79	I-GENE
+was	O
+unaffected	O
+on	O
+poly	O
+(	O
+dA	O
+)	O
+x	O
+oligo	O
+(	O
+dT	O
+)	O
+but	O
+was	O
+dramatically	O
+reduced	O
+on	O
+a	O
+natural	O
+template	O
+with	O
+secondary	O
+structure	O
+.	O
+
+Alanine	O
+substitution	O
+mutations	O
+in	O
+the	O
+Zta	B-GENE
+activation	I-GENE
+domain	I-GENE
+which	O
+eliminate	O
+the	O
+ability	O
+of	O
+Zta	B-GENE
+to	O
+stimulate	O
+the	O
+D	B-GENE
+-	I-GENE
+A	I-GENE
+complex	I-GENE
+were	O
+examined	O
+.	O
+
+The	O
+Scm	B-GENE
+and	O
+ph	B-GENE
+proteins	O
+share	O
+a	O
+homology	O
+domain	O
+with	O
+38	O
+%	O
+identity	O
+over	O
+a	O
+length	O
+of	O
+65	O
+amino	O
+acids	O
+,	O
+termed	O
+the	O
+SPM	O
+domain	O
+,	O
+that	O
+is	O
+located	O
+at	O
+their	O
+respective	O
+C	O
+termini	O
+.	O
+
+It	O
+has	O
+been	O
+previously	O
+shown	O
+that	O
+genes	O
+transcribed	O
+by	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+(	O
+RNAP	B-GENE
+II	I-GENE
+)	O
+are	O
+subject	O
+to	O
+position	O
+effect	O
+variegation	O
+when	O
+located	O
+near	O
+yeast	O
+telomeres	O
+.	O
+
+Likewise	O
+,	O
+rad6	B-GENE
+-	I-GENE
+delta	I-GENE
+reduces	O
+silencing	O
+of	O
+the	O
+telomere	B-GENE
+-	I-GENE
+located	I-GENE
+RNAP	I-GENE
+II	I-GENE
+-	I-GENE
+transcribed	I-GENE
+genes	I-GENE
+URA3	I-GENE
+and	O
+ADE2	B-GENE
+.	O
+
+The	O
+amplitude	O
+of	O
+detrusor	O
+contractions	O
+at	O
+6	O
+,	O
+12	O
+,	O
+and	O
+24	O
+hours	O
+showed	O
+no	O
+significant	O
+difference	O
+from	O
+that	O
+in	O
+the	O
+controls	O
+.	O
+
+In	O
+the	O
+predicted	O
+transmembrane	O
+domain	O
+,	O
+Casr	B-GENE
+-	I-GENE
+rs2	I-GENE
+and	O
+Casr	B-GENE
+-	I-GENE
+rs3	I-GENE
+are	O
+95	O
+%	O
+identical	O
+to	O
+Casr	B-GENE
+-	I-GENE
+rs1	I-GENE
+.	O
+
+PET	O
+activation	O
+studies	O
+are	O
+performed	O
+widely	O
+to	O
+study	O
+human	O
+brain	O
+function	O
+.	O
+
+F	B-GENE
+-	I-GENE
+box	I-GENE
+proteins	I-GENE
+are	O
+receptors	O
+that	O
+recruit	O
+phosphorylated	O
+substrates	O
+to	O
+the	O
+SCF	B-GENE
+ubiquitin	B-GENE
+-	O
+ligase	B-GENE
+complex	O
+.	O
+
+In	O
+the	O
+context	O
+of	O
+liver	O
+allograft	O
+shortage	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+an	O
+ELT	O
+should	O
+not	O
+be	O
+performed	O
+in	O
+patients	O
+with	O
+cardiac	O
+failure	O
+,	O
+more	O
+than	O
+two	O
+OSF	O
+,	O
+or	O
+an	O
+APACHE	O
+II	O
+score	O
+higher	O
+than	O
+30	O
+.	O
+
+The	O
+SH3	B-GENE
+domains	I-GENE
+of	O
+Grb2	B-GENE
+bound	O
+in	O
+vitro	O
+to	O
+specific	O
+proline	O
+-	O
+rich	O
+motifs	O
+in	O
+the	O
+HPK1	B-GENE
+tail	O
+and	O
+functioned	O
+synergistically	O
+to	O
+direct	O
+the	O
+stable	O
+binding	O
+of	O
+Grb2	B-GENE
+to	O
+HPK1	B-GENE
+in	O
+transfected	O
+Cos1	O
+cells	O
+.	O
+
+By	O
+far	O
+-	O
+Western	O
+analysis	O
+and	O
+coimmunoprecipitation	O
+studies	O
+,	O
+we	O
+demonstrate	O
+that	O
+ZNF74	B-GENE
+interacts	O
+,	O
+via	O
+its	O
+zinc	O
+finger	O
+domain	O
+,	O
+with	O
+the	O
+hyperphosphorylated	O
+largest	O
+subunit	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+(	O
+pol	B-GENE
+IIo	I-GENE
+)	O
+but	O
+not	O
+with	O
+the	O
+hypophosphorylated	O
+form	O
+.	O
+
+Thus	O
+,	O
+ZNF74	B-GENE
+sublocalization	O
+in	O
+nuclear	O
+domains	O
+enriched	O
+in	O
+pre	O
+-	O
+mRNA	O
+maturating	O
+factors	O
+,	O
+its	O
+RNA	O
+binding	O
+activity	O
+,	O
+and	O
+its	O
+direct	O
+phosphodependent	O
+interaction	O
+with	O
+the	O
+pol	B-GENE
+IIo	I-GENE
+,	O
+a	O
+form	O
+of	O
+the	O
+RNA	B-GENE
+polymerase	I-GENE
+functionally	O
+associated	O
+with	O
+pre	O
+-	O
+mRNA	O
+processing	O
+,	O
+suggest	O
+a	O
+role	O
+for	O
+this	O
+member	O
+of	O
+the	O
+KRAB	B-GENE
+multifinger	I-GENE
+protein	I-GENE
+family	I-GENE
+in	O
+RNA	O
+processing	O
+.	O
+
+Ki	B-GENE
+-	I-GENE
+ras4BVal	I-GENE
+-	I-GENE
+12	I-GENE
+transfectant	O
+cells	O
+expressed	O
+2	O
+-	O
+fold	O
+elevated	O
+protein	O
+levels	O
+of	O
+the	O
+lysosomal	B-GENE
+cysteine	I-GENE
+protease	I-GENE
+cathepsin	B-GENE
+B	I-GENE
+but	O
+did	O
+not	O
+up	O
+-	O
+regulate	O
+cathepsin	B-GENE
+B	I-GENE
+mRNA	I-GENE
+expression	O
+.	O
+
+The	O
+cellular	O
+rate	O
+of	O
+anticoagulant	B-GENE
+heparan	I-GENE
+sulfate	I-GENE
+proteoglycan	I-GENE
+(	O
+HSPGact	B-GENE
+)	O
+generation	O
+is	O
+determined	O
+by	O
+the	O
+level	O
+of	O
+a	O
+kinetically	O
+limiting	O
+microsomal	O
+activity	O
+,	O
+HSact	O
+conversion	O
+activity	O
+,	O
+which	O
+is	O
+predominantly	O
+composed	O
+of	O
+the	O
+long	O
+sought	O
+heparan	B-GENE
+sulfate	I-GENE
+D	I-GENE
+-	I-GENE
+glucosaminyl	I-GENE
+3	I-GENE
+-	I-GENE
+O	I-GENE
+-	I-GENE
+sulfotransferase	I-GENE
+(	O
+3	B-GENE
+-	I-GENE
+OST	I-GENE
+)	O
+(	O
+Shworak	O
+,	O
+N	O
+.	O
+
+Interestingly	O
+,	O
+EGF	B-GENE
+,	O
+but	O
+not	O
+insulin	B-GENE
+,	O
+stimulated	O
+tyrosine	O
+phosphorylation	O
+of	O
+c	B-GENE
+-	I-GENE
+cbl	I-GENE
+and	O
+its	O
+association	O
+with	O
+Crk	B-GENE
+-	I-GENE
+II	I-GENE
+.	O
+
+An	O
+end	O
+to	O
+the	O
+lottery	O
+.	O
+
+We	O
+previously	O
+showed	O
+that	O
+the	O
+N	O
+-	O
+terminal	O
+portion	O
+common	O
+to	O
+various	O
+chimeric	B-GENE
+MLL	I-GENE
+products	I-GENE
+,	O
+as	O
+well	O
+as	O
+to	O
+MLL	B-GENE
+-	I-GENE
+LTG9	I-GENE
+and	O
+MLL	B-GENE
+-	I-GENE
+LTG19	I-GENE
+,	O
+localizes	O
+in	O
+the	O
+nuclei	O
+,	O
+and	O
+therefore	O
+suggested	O
+that	O
+it	O
+might	O
+play	O
+an	O
+important	O
+role	O
+in	O
+leukemogenesis	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+the	O
+pattern	O
+of	O
+blood	O
+supply	O
+is	O
+relevant	O
+to	O
+the	O
+structural	O
+organisation	O
+of	O
+mature	O
+lamellar	O
+bone	O
+around	O
+the	O
+implant	O
+.	O
+
+Induction	O
+of	O
+AtP5CS1	B-GENE
+mRNA	I-GENE
+accumulation	O
+in	O
+salt	O
+-	O
+treated	O
+seedlings	O
+involves	O
+an	O
+immediate	O
+early	O
+transcriptional	O
+response	O
+regulated	O
+by	O
+ABA	O
+signalling	O
+that	O
+is	O
+not	O
+inhibited	O
+by	O
+cycloheximide	O
+,	O
+but	O
+abolished	O
+by	O
+the	O
+deficiency	O
+of	O
+ABA	O
+biosynthesis	O
+in	O
+the	O
+aba1	B-GENE
+Arabidopsis	I-GENE
+mutant	I-GENE
+.	O
+
+It	O
+thus	O
+appears	O
+that	O
+MAPK	B-GENE
+functions	O
+in	O
+meiotic	O
+maturation	O
+by	O
+preventing	O
+unfertilized	O
+eggs	O
+from	O
+proceeding	O
+into	O
+parthenogenetic	O
+development	O
+.	O
+
+A	O
+positive	O
+correlation	O
+between	O
+serum	B-GENE
+myoglobin	I-GENE
+and	O
+CA	B-GENE
+III	I-GENE
+concentrations	O
+(	O
+rs	O
+=	O
+0	O
+.	O
+933	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+was	O
+observed	O
+in	O
+hemodialyzed	O
+patients	O
+with	O
+chronic	O
+renal	O
+failure	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+over	O
+-	O
+replication	O
+phenotype	O
+produced	O
+by	O
+this	O
+mutant	B-GENE
+p65cdc18	I-GENE
+is	O
+resistant	O
+to	O
+increased	O
+mitotic	O
+cyclin	B-GENE
+/	O
+CDK	B-GENE
+activity	O
+,	O
+a	O
+known	O
+inhibitor	O
+of	O
+over	O
+-	O
+replication	O
+.	O
+
+Rip1p	B-GENE
+is	O
+inessential	O
+,	O
+associated	O
+with	O
+nuclear	O
+pore	O
+complexes	O
+,	O
+and	O
+structurally	O
+related	O
+to	O
+the	O
+FG	B-GENE
+-	I-GENE
+nucleoporin	I-GENE
+family	I-GENE
+of	O
+pore	O
+proteins	O
+.	O
+
+The	O
+CNXA	O
+domain	O
+is	O
+similar	O
+at	O
+the	O
+amino	O
+acid	O
+level	O
+to	O
+the	O
+Escherichia	B-GENE
+coli	I-GENE
+moaA	I-GENE
+gene	I-GENE
+product	I-GENE
+,	O
+while	O
+CNXC	O
+is	O
+similar	O
+to	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+moaC	I-GENE
+product	I-GENE
+,	O
+with	O
+both	O
+E	O
+.	O
+coli	O
+products	O
+encoded	O
+by	O
+different	O
+cistrons	O
+.	O
+
+Deletions	O
+in	O
+each	O
+of	O
+these	O
+regions	O
+abolish	O
+membrane	O
+localization	O
+of	O
+Tiam1	B-GENE
+and	O
+membrane	O
+ruffling	O
+,	O
+suggesting	O
+that	O
+they	O
+function	O
+cooperatively	O
+.	O
+
+However	O
+,	O
+besides	O
+the	O
+kinase	O
+catalytic	O
+domain	O
+and	O
+double	O
+leucine	O
+/	O
+isoleucine	O
+zippers	O
+,	O
+there	O
+was	O
+no	O
+significant	O
+homology	O
+with	O
+known	O
+proteins	O
+.	O
+
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+inhibition	O
+increased	O
+the	O
+binding	O
+of	O
+ARE	O
+(	O
+AUBP	O
+activity	O
+)	O
+and	O
+poly	O
+(	O
+U	O
+)	O
+-	O
+Sepharose	O
+by	O
+cytoplasmic	B-GENE
+hnRNP	I-GENE
+A1	I-GENE
+,	O
+while	O
+nuclear	B-GENE
+hnRNP	I-GENE
+A1	I-GENE
+binding	O
+was	O
+unaffected	O
+.	O
+
+Modulation	O
+of	O
+AUUUA	O
+response	O
+element	O
+binding	O
+by	O
+heterogeneous	B-GENE
+nuclear	I-GENE
+ribonucleoprotein	I-GENE
+A1	I-GENE
+in	O
+human	O
+T	O
+lymphocytes	O
+.	O
+
+Histological	O
+slides	O
+of	O
+one	O
+biopsy	O
+of	O
+each	O
+patient	O
+(	O
+formalin	O
+-	O
+fixed	O
+and	O
+paraffin	O
+-	O
+embedded	O
+)	O
+were	O
+stained	O
+with	O
+a	O
+Modified	O
+Giemsa	O
+(	O
+MG	O
+)	O
+,	O
+the	O
+Warthin	O
+-	O
+Starry	O
+(	O
+WS	O
+)	O
+,	O
+and	O
+an	O
+immunohistochemical	O
+method	O
+(	O
+IMM	O
+)	O
+using	O
+purified	O
+polyclonal	O
+H	O
+.	O
+pylori	O
+antiserum	O
+(	O
+DAKO	O
+B471	O
+)	O
+.	O
+
+Their	O
+biosynthesis	O
+proceeds	O
+via	O
+linear	O
+precursors	O
+that	O
+become	O
+branched	O
+by	O
+beta1	B-GENE
+,	I-GENE
+6	I-GENE
+-	I-GENE
+GlcNAc	I-GENE
+transferases	I-GENE
+(	O
+IGnT6	O
+,	O
+GlcNAc	O
+to	O
+Gal	O
+)	O
+.	O
+
+These	O
+findings	O
+indicate	O
+that	O
+the	O
+t	O
+(	O
+4	O
+;	O
+14	O
+)	O
+(	O
+p16	O
+.	O
+3	O
+;	O
+q32	O
+)	O
+represents	O
+a	O
+novel	O
+,	O
+recurrent	O
+chromosomal	O
+translocation	O
+in	O
+MM	O
+,	O
+and	O
+suggest	O
+that	O
+the	O
+FGFR3	B-GENE
+gene	I-GENE
+may	O
+be	O
+the	O
+target	O
+of	O
+this	O
+abnormality	O
+and	O
+thus	O
+contribute	O
+to	O
+tumorigenesis	O
+in	O
+MM	O
+.	O
+
+In	O
+addition	O
+,	O
+mutation	O
+of	O
+the	O
+Sp1	B-GENE
+site	I-GENE
+also	O
+significantly	O
+reduced	O
+promoter	O
+activity	O
+.	O
+
+Amino	O
+acid	O
+residues	O
+of	O
+beta	O
+1	O
+'	O
+,	O
+alpha	O
+A	O
+'	O
+,	O
+alpha	O
+B	O
+'	O
+,	O
+and	O
+the	O
+loop	O
+containing	O
+His539	O
+of	O
+the	O
+RNase	B-GENE
+H	I-GENE
+domain	I-GENE
+interact	O
+with	O
+the	O
+primer	O
+strand	O
+of	O
+the	O
+dsDNA	O
+.	O
+
+Moreover	O
+,	O
+in	O
+one	O
+patient	O
+with	O
+a	O
+sarcoma	O
+who	O
+underwent	O
+a	O
+leg	O
+-	O
+sparing	O
+procedure	O
+,	O
+no	O
+sciatic	O
+nerve	O
+enlargement	O
+was	O
+seen	O
+postoperatively	O
+.	O
+
+The	O
+full	O
+length	O
+cDNA	O
+sequence	O
+of	O
+a	O
+Type	B-GENE
+I	I-GENE
+transforming	I-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta	I-GENE
+(	I-GENE
+TGF	I-GENE
+-	I-GENE
+beta	I-GENE
+)	I-GENE
+receptor	I-GENE
+has	O
+been	O
+isolated	O
+from	O
+the	O
+filarial	O
+parasitic	O
+nematode	O
+Brugia	O
+pahangi	O
+.	O
+
+This	O
+sequence	O
+possessed	O
+homology	O
+with	O
+a	O
+methylation	O
+-	O
+sensitive	O
+promoter	O
+element	O
+,	O
+Enh2	O
+,	O
+present	O
+in	O
+the	O
+LTR	O
+of	O
+mouse	O
+intractisternal	O
+A	O
+-	O
+particles	O
+.	O
+
+Codon	O
+optimization	O
+for	O
+high	O
+-	O
+level	O
+expression	O
+of	O
+human	B-GENE
+erythropoietin	I-GENE
+(	O
+EPO	B-GENE
+)	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Parodoxical	O
+rise	O
+in	O
+urinary	B-GENE
+albumin	I-GENE
+levels	O
+after	O
+treatment	O
+of	O
+essential	O
+hypertension	O
+.	O
+
+20	O
+%	O
+of	O
+total	O
+HSL	B-GENE
+transcripts	I-GENE
+in	O
+human	O
+subcutaneous	O
+adipocytes	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+Rat7p	B-GENE
+/	O
+Nup159p	B-GENE
+is	O
+anchored	O
+within	O
+the	O
+NPC	O
+through	O
+its	O
+coiled	O
+-	O
+coil	O
+region	O
+and	O
+adjacent	O
+sequences	O
+.	O
+
+In	O
+a	O
+group	O
+of	O
+13	O
+patients	O
+with	O
+obliterative	O
+arteriopathies	O
+of	O
+the	O
+lower	O
+limbs	O
+the	O
+plasma	O
+levels	O
+of	O
+thrombomodulin	B-GENE
+(	O
+TM	B-GENE
+)	O
+,	O
+betathromboglobulin	B-GENE
+(	O
+beta	B-GENE
+-	I-GENE
+TG	I-GENE
+)	O
+,	O
+D	O
+-	O
+dimer	O
+(	O
+DD	O
+)	O
+and	O
+plasminogen	B-GENE
+activator	I-GENE
+-	I-GENE
+inhibitor	I-GENE
+(	O
+pAI	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+were	O
+measured	O
+,	O
+and	O
+compared	O
+to	O
+the	O
+values	O
+obtained	O
+from	O
+10	O
+healthy	O
+volunteers	O
+.	O
+
+These	O
+residues	O
+,	O
+Ile244	O
+at	O
+the	O
+extracellular	O
+end	O
+of	O
+transmembrane	O
+helix	O
+3	O
+,	O
+and	O
+Tyr318	O
+at	O
+the	O
+COOH	O
+-	O
+terminal	O
+portion	O
+of	O
+extracellular	O
+loop	O
+2	O
+,	O
+are	O
+replaced	O
+by	O
+Leu	O
+and	O
+Ile	O
+in	O
+the	O
+PTH	B-GENE
+-	I-GENE
+1	I-GENE
+receptor	I-GENE
+,	O
+respectively	O
+.	O
+
+We	O
+have	O
+now	O
+shown	O
+that	O
+in	O
+vivo	O
+phosphorylation	O
+of	O
+14	B-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+3	I-GENE
+zeta	I-GENE
+at	O
+the	O
+CKIalpha	B-GENE
+site	I-GENE
+(	I-GENE
+Thr	I-GENE
+-	I-GENE
+233	I-GENE
+)	I-GENE
+negatively	O
+regulates	O
+its	O
+binding	O
+to	O
+c	B-GENE
+-	I-GENE
+Raf	I-GENE
+,	O
+and	O
+may	O
+be	O
+important	O
+in	O
+Raf	B-GENE
+-	O
+mediated	O
+signal	O
+transduction	O
+.	O
+
+Mouse	B-GENE
+mast	I-GENE
+cell	I-GENE
+protease	I-GENE
+9	I-GENE
+,	O
+a	O
+novel	O
+member	O
+of	O
+the	O
+chromosome	O
+14	O
+family	O
+of	O
+serine	B-GENE
+proteases	I-GENE
+that	O
+is	O
+selectively	O
+expressed	O
+in	O
+uterine	O
+mast	O
+cells	O
+.	O
+
+A	O
+DNase	B-GENE
+I	I-GENE
+-	I-GENE
+hypersensitive	I-GENE
+site	I-GENE
+has	O
+also	O
+been	O
+mapped	O
+in	O
+the	O
+258	O
+-	O
+base	O
+pair	O
+enhancer	O
+region	O
+.	O
+
+Together	O
+,	O
+our	O
+results	O
+show	O
+that	O
+tinman	B-GENE
+is	O
+controlled	O
+by	O
+an	O
+array	O
+of	O
+discrete	O
+enhancer	O
+elements	O
+that	O
+are	O
+activated	O
+successively	O
+by	O
+differential	O
+genetic	O
+inputs	O
+,	O
+as	O
+well	O
+as	O
+by	O
+closely	O
+linked	O
+activator	O
+and	O
+repressor	O
+binding	O
+sites	O
+within	O
+an	O
+early	O
+-	O
+acting	O
+enhancer	O
+,	O
+which	O
+restrict	O
+twist	B-GENE
+activity	O
+to	O
+specific	O
+areas	O
+within	O
+the	O
+twist	B-GENE
+expression	I-GENE
+domain	I-GENE
+.	O
+
+The	O
+Fis	B-GENE
+protein	I-GENE
+regulates	O
+site	O
+-	O
+specific	O
+DNA	O
+inversion	O
+catalyzed	O
+by	O
+a	O
+family	O
+of	O
+DNA	B-GENE
+invertases	I-GENE
+when	O
+bound	O
+to	O
+a	O
+cis	O
+-	O
+acting	O
+recombinational	O
+enhancer	O
+.	O
+
+The	O
+cell	O
+cycle	O
+-	O
+regulated	O
+transcription	O
+factor	O
+E2F	B-GENE
+is	O
+also	O
+known	O
+to	O
+bend	O
+DNA	O
+upon	O
+binding	O
+.	O
+
+Our	O
+study	O
+reveals	O
+that	O
+the	O
+modular	O
+structure	O
+of	O
+the	O
+FSH	B-GENE
+receptor	I-GENE
+gene	O
+generates	O
+motifs	O
+that	O
+allows	O
+coupling	O
+to	O
+different	O
+effectors	O
+.	O
+
+Transcriptional	O
+regulation	O
+of	O
+SUP35	B-GENE
+and	O
+SUP45	B-GENE
+in	I-GENE
+Saccharomyces	I-GENE
+cerevisiae	I-GENE
+.	O
+
+These	O
+studies	O
+serve	O
+as	O
+the	O
+basis	O
+for	O
+the	O
+further	O
+characterization	O
+of	O
+the	O
+regulatory	O
+mechanism	O
+of	O
+aromatase	B-GENE
+expression	O
+in	O
+human	O
+breast	O
+cancer	O
+and	O
+ASCs	O
+.	O
+
+Xenopus	B-GENE
+Ran	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+:	O
+molecular	O
+interactions	O
+and	O
+effects	O
+on	O
+nuclear	O
+assembly	O
+in	O
+Xenopus	O
+egg	O
+extracts	O
+.	O
+
+She	O
+improved	O
+with	O
+a	O
+combination	O
+of	O
+benzodiazepines	O
+and	O
+the	O
+acetylcholinesterase	B-GENE
+inhibitor	O
+physostigmine	O
+.	O
+
+METHODS	O
+:	O
+Total	O
+muscle	O
+paralysis	O
+was	O
+induced	O
+under	O
+general	O
+anesthesia	O
+in	O
+a	O
+group	O
+of	O
+obese	O
+persons	O
+(	O
+n	O
+=	O
+9	O
+;	O
+body	O
+mass	O
+index	O
+,	O
+32	O
++	O
+/	O
+-	O
+3	O
+kg	O
+[	O
+-	O
+2	O
+]	O
+)	O
+and	O
+in	O
+a	O
+group	O
+of	O
+nonobese	O
+persons	O
+(	O
+n	O
+=	O
+9	O
+;	O
+body	O
+mas	O
+index	O
+,	O
+21	O
++	O
+/	O
+-	O
+2	O
+kg	O
+[	O
+-	O
+2	O
+]	O
+)	O
+.	O
+
+PKA	B-GENE
+phosphorylated	O
+WT1	B-GENE
+at	O
+Ser	O
+-	O
+365	O
+and	O
+Ser	O
+-	O
+393	O
+in	O
+vitro	O
+,	O
+as	O
+well	O
+as	O
+at	O
+additional	O
+sites	O
+,	O
+and	O
+this	O
+phosphorylation	O
+abolished	O
+the	O
+DNA	O
+-	O
+binding	O
+activity	O
+of	O
+WT1	B-GENE
+in	O
+vitro	O
+.	O
+
+Our	O
+findings	O
+provide	O
+the	O
+first	O
+evidence	O
+that	O
+the	O
+function	O
+of	O
+WT1	B-GENE
+can	O
+be	O
+modulated	O
+by	O
+its	O
+phosphorylation	O
+in	O
+vivo	O
+.	O
+
+A	O
+second	O
+aim	O
+was	O
+to	O
+determine	O
+whether	O
+the	O
+decrease	O
+in	O
+muscle	O
+-	O
+tendon	O
+unit	O
+rest	O
+length	O
+produced	O
+by	O
+prolonged	O
+immobilisation	O
+in	O
+a	O
+shortened	O
+position	O
+is	O
+mediated	O
+primarily	O
+by	O
+adaptations	O
+of	O
+the	O
+muscle	O
+or	O
+tendon	O
+.	O
+
+The	O
+presence	O
+of	O
+an	O
+additional	O
+sequence	O
+of	O
+nucleotides	O
+145	O
+-	O
+165	O
+from	O
+the	O
+3	O
+'	O
+end	O
+of	O
+RNA3	B-GENE
+enhanced	O
+template	O
+recognition	O
+by	O
+RdRp	B-GENE
+in	O
+vitro	O
+and	O
+accumulation	O
+of	O
+RNA3	B-GENE
+in	O
+vivo	O
+to	O
+wild	O
+-	O
+type	O
+levels	O
+.	O
+
+We	O
+argue	O
+that	O
+the	O
+primary	O
+role	O
+of	O
+hh	B-GENE
+in	O
+controlling	O
+polarity	O
+is	O
+to	O
+cause	O
+anterior	O
+compartment	O
+cells	O
+to	O
+reverse	O
+their	O
+interpretation	O
+of	O
+an	O
+underlying	O
+symmetric	O
+polarization	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+study	O
+suggest	O
+that	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activity	O
+may	O
+be	O
+regulated	O
+by	O
+its	O
+interaction	O
+with	O
+the	O
+cell	O
+cycle	O
+regulatory	O
+protein	O
+,	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+The	O
+lysozyme	B-GENE
+FEF	B-GENE
+site	O
+is	O
+immediately	O
+5	O
+'	O
+to	O
+a	O
+PU	B-GENE
+.	O
+
+Osteocalcin	B-GENE
+(	O
+OC	B-GENE
+)	O
+is	O
+a	O
+matrix	B-GENE
+calcium	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+expressed	O
+in	O
+osteoblasts	O
+and	O
+odontoblasts	O
+undergoing	O
+mineralization	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+examine	O
+the	O
+effects	O
+of	O
+Msx2	B-GENE
+expression	O
+on	O
+OC	B-GENE
+promoter	I-GENE
+activation	O
+(	O
+luciferase	B-GENE
+reporter	I-GENE
+)	O
+by	O
+FGF2	B-GENE
+/	O
+FSK	B-GENE
+and	O
+calcitriol	O
+in	O
+MC3T3	O
+-	O
+E1	O
+osteoblasts	O
+.	O
+
+Thus	O
+,	O
+unlike	O
+other	O
+proteins	O
+reported	O
+to	O
+inhibit	O
+SRF	B-GENE
+activity	O
+,	O
+the	O
+repressor	O
+activity	O
+associated	O
+with	O
+the	O
+GC	O
+-	O
+rich	O
+element	O
+does	O
+not	O
+appear	O
+to	O
+function	O
+through	O
+direct	O
+inhibition	O
+of	O
+SRF	B-GENE
+binding	O
+.	O
+
+However	O
+,	O
+one	O
+CAK	B-GENE
+-	O
+phosphorylated	O
+phosphopeptide	O
+comigrates	O
+with	O
+a	O
+Cdc2	B-GENE
+-	O
+phosphorylated	O
+phosphopeptide	O
+previously	O
+shown	O
+to	O
+be	O
+mitosis	O
+-	O
+specific	O
+,	O
+suggesting	O
+that	O
+,	O
+in	O
+vitro	O
+,	O
+CAK	B-GENE
+is	O
+able	O
+to	O
+phosphorylate	O
+at	O
+least	O
+one	O
+site	O
+that	O
+is	O
+also	O
+phosphorylated	O
+in	O
+vivo	O
+.	O
+
+The	O
+pen	O
+can	O
+heal	O
+.	O
+
+The	O
+mHIF	B-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+structural	I-GENE
+gene	I-GENE
+is	O
+composed	O
+of	O
+15	O
+exons	O
+.	O
+
+However	O
+,	O
+when	O
+a	O
+second	O
+,	O
+upstream	B-GENE
+IRE	I-GENE
+-	I-GENE
+like	I-GENE
+sequence	I-GENE
+was	O
+evaluated	O
+by	O
+EMSA	O
+,	O
+a	O
+DNA	O
+binding	O
+pattern	O
+distinct	O
+from	O
+that	O
+seen	O
+following	O
+exposure	O
+to	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+alone	O
+was	O
+observed	O
+after	O
+prolonged	O
+stimulation	O
+with	O
+both	O
+IFN	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+.	O
+
+In	O
+Arabidopsis	O
+,	O
+the	O
+induction	O
+of	O
+a	O
+dehydration	O
+-	O
+responsive	O
+gene	O
+,	O
+rd22	B-GENE
+,	O
+is	O
+mediated	O
+by	O
+abscisic	O
+acid	O
+(	O
+ABA	O
+)	O
+and	O
+requires	O
+protein	O
+biosynthesis	O
+for	O
+ABA	O
+-	O
+dependent	O
+gene	O
+expression	O
+.	O
+
+A	O
+cDNA	O
+encoding	O
+a	O
+MYC	B-GENE
+-	I-GENE
+related	I-GENE
+DNA	I-GENE
+binding	I-GENE
+protein	I-GENE
+was	O
+isolated	O
+by	O
+DNA	O
+-	O
+ligand	O
+binding	O
+screening	O
+,	O
+using	O
+the	O
+67	O
+-	O
+bp	O
+region	O
+as	O
+a	O
+probe	O
+,	O
+and	O
+designated	O
+rd22BP1	B-GENE
+.	O
+
+Human	B-GENE
+PDK1	I-GENE
+is	O
+homologous	O
+to	O
+the	O
+Drosophila	B-GENE
+protein	I-GENE
+kinase	I-GENE
+DSTPK61	I-GENE
+,	O
+which	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+regulation	O
+of	O
+sex	O
+differentiation	O
+,	O
+oogenesis	O
+and	O
+spermatogenesis	O
+.	O
+
+Thus	O
+,	O
+the	O
+synergistic	O
+effects	O
+of	O
+HNF	B-GENE
+-	I-GENE
+1beta	I-GENE
+and	O
+the	O
+GR	B-GENE
+on	O
+dexamethasone	O
+-	O
+stimulated	O
+promoter	O
+activity	O
+require	O
+that	O
+they	O
+are	O
+bound	O
+to	O
+the	O
+HNF	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+and	O
+the	O
+GRE	O
+,	O
+respectively	O
+,	O
+and	O
+may	O
+involve	O
+protein	O
+-	O
+protein	O
+interactions	O
+between	O
+the	O
+transcription	O
+factors	O
+,	O
+or	O
+between	O
+them	O
+and	O
+the	O
+basal	O
+transcription	O
+machinery	O
+or	O
+a	O
+steroid	B-GENE
+receptor	I-GENE
+coactivator	I-GENE
+.	O
+
+Mutational	O
+analysis	O
+shows	O
+that	O
+both	O
+an	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+like	I-GENE
+sequence	I-GENE
+(	O
+-	O
+294	O
+/	O
+-	O
+285	O
+,	O
+TGAATCATCA	O
+)	O
+and	O
+an	O
+A	O
+/	O
+T	O
+-	O
+rich	O
+myocyte	B-GENE
+enhancer	I-GENE
+factor	I-GENE
+(	I-GENE
+MEF	I-GENE
+)	I-GENE
+-	I-GENE
+2	I-GENE
+like	I-GENE
+sequence	I-GENE
+(	O
+-	O
+310	O
+/	O
+-	O
+298	O
+,	O
+TTAAAAATAAAAA	O
+)	O
+in	O
+the	O
+33	O
+-	O
+bp	O
+region	O
+are	O
+necessary	O
+for	O
+the	O
+OP	B-GENE
+-	I-GENE
+1	I-GENE
+effect	O
+.	O
+
+Unlike	O
+most	O
+other	O
+members	O
+of	O
+the	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+family	I-GENE
+,	O
+BAD	B-GENE
+(	O
+Bcl	B-GENE
+-	I-GENE
+xL	I-GENE
+/	I-GENE
+Bcl	I-GENE
+-	I-GENE
+2	I-GENE
+associated	I-GENE
+death	I-GENE
+promoter	I-GENE
+)	O
+,	O
+a	O
+death	B-GENE
+enhancer	I-GENE
+,	O
+has	O
+no	O
+C	O
+-	O
+terminal	O
+transmembrane	O
+domain	O
+for	O
+targeting	O
+to	O
+the	O
+outer	O
+mitochondrial	O
+membrane	O
+and	O
+nuclear	O
+envelope	O
+.	O
+
+An	O
+open	O
+reading	O
+frame	O
+of	O
+2862	O
+bp	O
+encoding	O
+a	O
+954	O
+amino	O
+acid	O
+protein	O
+was	O
+identified	O
+.	O
+
+One	O
+of	O
+these	O
+,	O
+an	O
+AACA	O
+motif	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+a	O
+negative	O
+regulator	O
+in	O
+non	O
+-	O
+seed	O
+tissues	O
+and	O
+has	O
+a	O
+similarity	O
+to	O
+the	O
+barley	O
+gibberellin	O
+responsive	O
+element	O
+recognized	O
+by	O
+MYB	B-GENE
+-	I-GENE
+like	I-GENE
+DNA	I-GENE
+binding	I-GENE
+proteins	I-GENE
+.	O
+
+Strain	O
+CFN037	O
+is	O
+an	O
+R	O
+.	O
+etli	O
+mutant	O
+induced	O
+by	O
+a	O
+single	O
+Tn5mob	B-GENE
+insertion	O
+in	O
+the	O
+promoter	O
+region	O
+of	O
+the	O
+thiCOGE	B-GENE
+gene	I-GENE
+cluster	I-GENE
+.	O
+
+Expression	O
+of	O
+thiamin	O
+biosynthetic	O
+genes	O
+(	O
+thiCOGE	B-GENE
+)	O
+and	O
+production	O
+of	O
+symbiotic	B-GENE
+terminal	I-GENE
+oxidase	I-GENE
+cbb3	I-GENE
+in	O
+Rhizobium	O
+etli	O
+.	O
+
+We	O
+have	O
+cloned	O
+and	O
+sequenced	O
+a	O
+region	O
+encoding	O
+a	O
+lipase	B-GENE
+operon	I-GENE
+and	O
+a	O
+putative	O
+,	O
+previously	O
+uncharacterized	O
+metalloprotease	B-GENE
+of	I-GENE
+Vibrio	I-GENE
+cholerae	I-GENE
+O1	I-GENE
+.	O
+
+Furthermore	O
+,	O
+the	O
+amount	O
+of	O
+tRNA	B-GENE
+(	I-GENE
+3Lys	I-GENE
+)	I-GENE
+that	O
+was	O
+placed	O
+onto	O
+viral	O
+RNA	O
+in	O
+mutated	O
+viruses	O
+was	O
+significantly	O
+less	O
+than	O
+that	O
+placed	O
+in	O
+the	O
+wild	O
+-	O
+type	O
+virus	O
+.	O
+
+This	O
+protein	O
+is	O
+present	O
+in	O
+both	O
+HeLa	O
+nuclear	O
+extracts	O
+and	O
+S100	B-GENE
+extracts	O
+but	O
+absent	O
+from	O
+SR	B-GENE
+protein	I-GENE
+preparations	O
+,	O
+suggesting	O
+that	O
+it	O
+is	O
+not	O
+a	O
+classical	O
+SR	B-GENE
+protein	I-GENE
+.	O
+
+Acad	O
+.	O
+
+Chimeras	O
+containing	O
+IE1	B-GENE
+peptides	I-GENE
+dramatically	O
+activated	O
+transcription	O
+of	O
+the	O
+basal	O
+promoter	O
+only	O
+when	O
+lac	B-GENE
+operator	I-GENE
+sequences	I-GENE
+were	O
+present	O
+.	O
+
+The	O
+results	O
+of	O
+replicase	B-GENE
+assays	O
+performed	O
+with	O
+mutant	B-GENE
+VP2	I-GENE
+containing	O
+a	O
+deletion	O
+in	O
+its	O
+RNA	O
+-	O
+binding	O
+domain	O
+suggests	O
+that	O
+the	O
+essential	O
+role	O
+for	O
+VP2	B-GENE
+in	O
+replication	O
+is	O
+linked	O
+to	O
+the	O
+protein	O
+'	O
+s	O
+ability	O
+to	O
+bind	O
+the	O
+mRNA	O
+template	O
+for	O
+minus	O
+-	O
+strand	O
+synthesis	O
+.	O
+
+We	O
+previously	O
+described	O
+two	O
+alanine	O
+cluster	O
+mutations	O
+,	O
+R77	O
+to	O
+A	O
+(	O
+R77A	O
+)	O
+-	O
+K79A	O
+and	O
+E192A	O
+-	O
+E194A	O
+,	O
+which	O
+selectively	O
+inactivated	O
+the	O
+triphosphatase	O
+component	O
+.	O
+
+Transfection	O
+of	O
+HepG2	O
+and	O
+SK	O
+-	O
+N	O
+-	O
+MC	O
+cells	O
+with	O
+constructs	O
+deleted	O
+of	O
+additional	O
+5	O
+'	O
+-	O
+flanking	O
+fragments	O
+permitted	O
+the	O
+definition	O
+of	O
+a	O
+minimal	O
+200	O
+bp	O
+promoter	O
+fragment	O
+containing	O
+the	O
+pseudo	O
+-	O
+TATA	O
+box	O
+and	O
+two	O
+putative	O
+SP1	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+Both	O
+inserts	O
+are	O
+larger	O
+than	O
+their	O
+homologues	O
+in	O
+eIF	B-GENE
+-	I-GENE
+2alpha	I-GENE
+kinases	I-GENE
+.	O
+
+Three	O
+monopolar	O
+electrodes	O
+were	O
+inserted	O
+into	O
+the	O
+left	O
+and	O
+right	O
+lateral	O
+vestibulospinal	O
+tract	O
+(	O
+LVST	O
+)	O
+and	O
+medial	O
+vestibulospinal	O
+tract	O
+(	O
+MVST	O
+)	O
+of	O
+the	O
+C1	O
+segment	O
+,	O
+to	O
+determine	O
+the	O
+pathway	O
+of	O
+axons	O
+.	O
+
+Epitopes	O
+of	O
+adhesion	O
+-	O
+perturbing	O
+monoclonal	O
+antibodies	O
+map	O
+within	O
+a	O
+predicted	O
+alpha	O
+-	O
+helical	O
+domain	O
+of	O
+the	O
+integrin	B-GENE
+beta	I-GENE
+1	I-GENE
+subunit	I-GENE
+.	O
+
+Polyhomeotic	B-GENE
+and	I-GENE
+Posterior	I-GENE
+Sex	I-GENE
+Combs	I-GENE
+may	O
+participate	O
+in	O
+a	O
+more	O
+general	O
+transcriptional	O
+mechanism	O
+that	O
+causes	O
+modulated	O
+gene	O
+repression	O
+,	O
+whereas	O
+the	O
+inclusion	O
+of	O
+Polycomb	B-GENE
+protein	I-GENE
+in	O
+the	O
+complex	O
+at	O
+PREs	B-GENE
+leads	O
+to	O
+stable	O
+silencing	O
+.	O
+
+Furthermore	O
+,	O
+both	O
+rhHR23	B-GENE
+proteins	I-GENE
+function	O
+in	O
+a	O
+defined	O
+NER	O
+system	O
+reconstituted	O
+with	O
+purified	O
+proteins	O
+,	O
+indicating	O
+direct	O
+involvement	O
+of	O
+hHR23	B-GENE
+proteins	I-GENE
+in	O
+the	O
+DNA	O
+repair	O
+reaction	O
+via	O
+interaction	O
+with	O
+XPC	B-GENE
+.	O
+
+The	O
+yeast	O
+silent	B-GENE
+information	I-GENE
+regulator	I-GENE
+Sir4p	I-GENE
+anchors	O
+and	O
+partitions	O
+plasmids	O
+.	O
+
+Polysome	O
+analyses	O
+in	O
+a	O
+temperature	O
+-	O
+sensitive	O
+fal1	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+and	O
+a	O
+Fal1p	B-GENE
+-	O
+depleted	O
+strain	O
+reveal	O
+a	O
+decrease	O
+in	O
+the	O
+number	O
+of	O
+40S	B-GENE
+ribosomal	I-GENE
+subunits	I-GENE
+.	O
+
+Sequence	O
+analysis	O
+identified	O
+some	O
+of	O
+these	O
+cDNA	O
+clones	O
+as	O
+Dlc	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+a	O
+sequence	O
+encoding	O
+a	O
+small	O
+,	O
+9	B-GENE
+-	I-GENE
+kDa	I-GENE
+human	I-GENE
+homolog	I-GENE
+of	I-GENE
+the	I-GENE
+outer	I-GENE
+-	I-GENE
+arm	I-GENE
+dynein	I-GENE
+light	I-GENE
+-	I-GENE
+chain	I-GENE
+protein	O
+.	O
+
+Importantly	O
+,	O
+in	O
+HeLa	O
+and	O
+293	O
+cells	O
+,	O
+endogenous	O
+and	O
+transfected	O
+I	B-GENE
+kappaB	I-GENE
+alpha	I-GENE
+coimmunoprecipitated	O
+with	O
+Myc	B-GENE
+-	O
+tagged	O
+or	O
+endogenous	O
+Dlc	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Identification	O
+of	O
+dynein	B-GENE
+heavy	I-GENE
+chain	I-GENE
+genes	I-GENE
+expressed	O
+in	O
+human	O
+and	O
+mouse	O
+testis	O
+:	O
+chromosomal	O
+localization	O
+of	O
+an	O
+axonemal	B-GENE
+dynein	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+proposed	O
+mechanism	O
+of	O
+effect	O
+states	O
+that	O
+mono	O
+(	O
+2	O
+-	O
+ethylhexyl	O
+)	O
+phthalate	O
+(	O
+MEHP	O
+)	O
+,	O
+the	O
+primary	O
+hydrolysis	O
+product	O
+of	O
+DEHP	O
+,	O
+mimics	O
+the	O
+inducing	O
+prostaglandins	O
+(	O
+PG	O
+)	O
+PGD	O
+(	O
+2	O
+)	O
+,	O
+9alpha	O
+,	O
+11betaPGF2	O
+,	O
+and	O
+PGF2alpha	O
+,	O
+and	O
+thromboxanes	O
+in	O
+the	O
+lungs	O
+,	O
+thereby	O
+increasing	O
+the	O
+risk	O
+of	O
+inducing	O
+inflammation	O
+in	O
+the	O
+airways	O
+,	O
+which	O
+is	O
+a	O
+characteristic	O
+of	O
+asthma	O
+.	O
+
+We	O
+found	O
+14	O
+protein	O
+binding	O
+sites	O
+that	O
+were	O
+occupied	O
+in	O
+vivo	O
+.	O
+
+Constitutive	O
+protection	O
+of	O
+E2F	B-GENE
+recognition	I-GENE
+sequences	I-GENE
+in	O
+the	O
+human	B-GENE
+thymidine	I-GENE
+kinase	I-GENE
+promoter	I-GENE
+during	O
+cell	O
+cycle	O
+progression	O
+.	O
+
+Comparison	O
+of	O
+genomic	O
+sequence	O
+shows	O
+that	O
+the	O
+ph	B-GENE
+locus	I-GENE
+has	O
+been	O
+duplicated	O
+,	O
+and	O
+that	O
+it	O
+contains	O
+proximal	O
+and	O
+distal	O
+transcription	O
+units	O
+.	O
+
+Radiation	O
+decreased	O
+the	O
+levels	O
+of	O
+T4	O
+and	O
+T3	O
+6	O
+h	O
+and	O
+72	O
+h	O
+in	O
+group	O
+C	O
+,	O
+in	O
+group	O
+A	O
+at	O
+72	O
+h	O
+,	O
+in	O
+group	O
+B	O
+at	O
+24	O
+h	O
+postexposure	O
+.	O
+
+We	O
+have	O
+reviewed	O
+the	O
+experience	O
+of	O
+a	O
+major	O
+MMT	O
+general	O
+practice	O
+with	O
+hepatitis	O
+C	O
+virus	O
+(	O
+HCV	O
+)	O
+infection	O
+from	O
+1991	O
+to	O
+1995	O
+.	O
+
+The	O
+author	O
+analyzes	O
+extensive	O
+own	O
+data	O
+based	O
+on	O
+study	O
+into	O
+particular	O
+features	O
+of	O
+cardiovascular	O
+disorders	O
+in	O
+chronic	O
+renal	O
+impairement	O
+with	O
+making	O
+use	O
+of	O
+modern	O
+diagnostic	O
+tools	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+characterization	O
+is	O
+given	O
+of	O
+clinical	O
+and	O
+biochemical	O
+features	O
+of	O
+VH	O
+B	O
+course	O
+against	O
+the	O
+background	O
+of	O
+narcomania	O
+.	O
+
+447	O
+microns	O
+for	O
+A	O
+.	O
+microcephalum	O
+and	O
+350	O
+microns	O
+for	O
+A	O
+.	O
+wedli	O
+)	O
+,	O
+and	O
+fewer	O
+testes	O
+per	O
+proglottis	O
+(	O
+44	O
+-	O
+73	O
+vs	O
+.	O
+
+The	O
+ZnF20	B-GENE
+cDNA	I-GENE
+hybridized	O
+to	O
+multiple	O
+transcripts	O
+in	O
+a	O
+thyroid	O
+cancer	O
+cell	O
+line	O
+(	O
+8	O
+.	O
+0	O
+,	O
+4	O
+.	O
+5	O
+and	O
+2	O
+kb	O
+)	O
+that	O
+increased	O
+after	O
+cycloheximide	O
+treatment	O
+and	O
+decayed	O
+<	O
+2	O
+h	O
+after	O
+addition	O
+of	O
+actinomycin	O
+D	O
+.	O
+
+Glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+(	O
+GST	B-GENE
+)	O
+-	O
+E2F	B-GENE
+and	O
+GST	B-GENE
+-	O
+DP	B-GENE
+fusion	O
+proteins	O
+were	O
+found	O
+to	O
+cooperate	O
+in	O
+binding	O
+to	O
+the	O
+three	O
+E2F	B-GENE
+sites	I-GENE
+in	O
+the	O
+DNA	B-GENE
+polymerase	I-GENE
+alpha	I-GENE
+gene	I-GENE
+promoter	I-GENE
+in	O
+vitro	O
+.	O
+
+Two	O
+sterol	O
+regulatory	O
+element	O
+-	O
+like	O
+sequences	O
+mediate	O
+up	O
+-	O
+regulation	O
+of	O
+caveolin	B-GENE
+gene	I-GENE
+transcription	O
+in	O
+response	O
+to	O
+low	B-GENE
+density	I-GENE
+lipoprotein	I-GENE
+free	O
+cholesterol	O
+.	O
+
+Furthermore	O
+,	O
+DNA	O
+-	O
+bound	O
+LAZ3	B-GENE
+/	O
+BCL6	B-GENE
+recruits	O
+SMRT	B-GENE
+in	O
+vivo	O
+,	O
+and	O
+both	O
+overexpressed	O
+proteins	O
+completely	O
+colocalize	O
+in	O
+nuclear	O
+dots	O
+.	O
+
+CONCLUSIONS	O
+:	O
+We	O
+obtained	O
+normal	O
+EPO	B-GENE
+levels	O
+for	O
+mothers	O
+and	O
+newborns	O
+for	O
+our	O
+area	O
+,	O
+similarly	O
+to	O
+the	O
+previously	O
+described	O
+ones	O
+.	O
+
+Ischaemia	O
+was	O
+induced	O
+by	O
+a	O
+low	O
+flow	O
+rate	O
+of	O
+0	O
+.	O
+8	O
+mL	O
+min	O
+-	O
+1	O
+for	O
+30	O
+min	O
+,	O
+and	O
+was	O
+followed	O
+by	O
+a	O
+40	O
+-	O
+minute	O
+reperfusion	O
+.	O
+
+BACKGROUND	O
+:	O
+Checkpoint	O
+pathways	O
+prevent	O
+cell	O
+-	O
+cycle	O
+progression	O
+in	O
+the	O
+event	O
+of	O
+DNA	O
+lesions	O
+.	O
+
+Direct	O
+proof	O
+that	O
+the	O
+heightened	O
+renal	O
+cellular	O
+apoptosis	O
+in	O
+PKD	O
+is	O
+not	O
+occurring	O
+through	O
+p53	B-GENE
+was	O
+obtained	O
+by	O
+successive	O
+matings	O
+between	O
+SBM	O
+and	O
+p53	B-GENE
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+.	O
+
+Accumulated	O
+evidence	O
+indicates	O
+that	O
+,	O
+upon	O
+stimulation	O
+with	O
+interferon	B-GENE
+-	I-GENE
+gamma	I-GENE
+(	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+)	O
+,	O
+three	O
+beta	O
+-	O
+type	O
+subunits	O
+,	O
+designated	O
+LMP2	B-GENE
+,	O
+LMP7	B-GENE
+,	O
+and	O
+PSMB10	B-GENE
+,	O
+are	O
+incorporated	O
+into	O
+the	O
+20S	B-GENE
+proteasome	I-GENE
+by	O
+displacing	O
+the	O
+housekeeping	O
+beta	O
+-	O
+type	O
+subunits	O
+designated	O
+PSMB6	B-GENE
+,	O
+PSMB5	B-GENE
+,	O
+and	O
+PSMB7	B-GENE
+,	O
+respectively	O
+.	O
+
+The	O
+major	O
+RNase	B-GENE
+E	I-GENE
+cleavage	O
+product	O
+(	O
+denoted	O
+pSok	B-GENE
+-	I-GENE
+6	I-GENE
+)	O
+is	O
+rapidly	O
+degraded	O
+by	O
+polynucleotide	B-GENE
+phosphorylase	I-GENE
+(	O
+PNPase	B-GENE
+)	O
+.	O
+
+This	O
+difference	O
+may	O
+result	O
+from	O
+the	O
+lower	O
+match	O
+to	O
+the	O
+ARG	O
+box	O
+consensus	O
+of	O
+the	O
+O	B-GENE
+(	I-GENE
+rocD	I-GENE
+)	I-GENE
+site	I-GENE
+.	O
+
+Ask	O
+AONE	O
+'	O
+s	O
+experts	O
+.	O
+.	O
+.	O
+about	O
+productivity	O
+indicators	O
+.	O
+
+All	O
+pigs	O
+had	O
+significant	O
+regional	O
+LV	O
+dysfunction	O
+and	O
+reduced	O
+LV	O
+ejection	O
+fraction	O
+(	O
+41	O
++	O
+/	O
+-	O
+11	O
+%	O
+)	O
+.	O
+
+The	O
+progress	O
+of	O
+morphological	O
+research	O
+on	O
+the	O
+parabrachial	O
+nucleus	O
+
+The	O
+amplitudes	O
+of	O
+DPOAE	O
+also	O
+recovered	O
+to	O
+a	O
+greater	O
+extent	O
+and	O
+outer	O
+hair	O
+cell	O
+losses	O
+were	O
+less	O
+severe	O
+in	O
+the	O
+R	O
+-	O
+PIA	O
+-	O
+treated	O
+ears	O
+.	O
+
+The	O
+data	O
+provide	O
+evidence	O
+both	O
+for	O
+a	O
+signal	O
+transduction	O
+pathway	O
+independent	O
+of	O
+JNK	B-GENE
+,	O
+ERK	B-GENE
+,	O
+and	O
+p38	B-GENE
+MAP	B-GENE
+kinase	I-GENE
+to	O
+be	O
+involved	O
+in	O
+the	O
+induction	O
+of	O
+rhoB	B-GENE
+by	O
+genotoxic	O
+stress	O
+,	O
+and	O
+furthermore	O
+,	O
+indicate	O
+autoregulation	O
+of	O
+rhoB	B-GENE
+.	O
+
+In	O
+an	O
+effort	O
+to	O
+separate	O
+domains	O
+of	O
+FadR	B-GENE
+required	O
+for	O
+DNA	O
+binding	O
+,	O
+dimerization	O
+,	O
+and	O
+ligand	O
+binding	O
+,	O
+chimeric	O
+protein	O
+fusions	O
+between	O
+the	O
+DNA	O
+binding	O
+domain	O
+of	O
+LexA	B-GENE
+and	O
+different	O
+regions	O
+of	O
+FadR	B-GENE
+were	O
+constructed	O
+.	O
+
+Inhibition	O
+appears	O
+to	O
+result	O
+from	O
+titration	O
+of	O
+general	O
+transcription	O
+factors	O
+because	O
+MDM2	B-GENE
+overexpression	O
+inhibits	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+as	O
+well	O
+as	O
+other	O
+promoters	O
+in	O
+vivo	O
+and	O
+basal	O
+transcription	O
+in	O
+vitro	O
+.	O
+
+4	O
+)	O
+PU	B-GENE
+and	O
+PD	B-GENE
+lacked	O
+the	O
+canonical	O
+TATA	O
+or	O
+CAAT	O
+motifs	O
+,	O
+and	O
+are	O
+AT	O
+-	O
+rich	O
+.	O
+
+The	O
+mobility	O
+shift	O
+of	O
+both	O
+of	O
+these	O
+proteins	O
+is	O
+abolished	O
+by	O
+treatment	O
+with	O
+inhibitors	O
+of	O
+PKC	B-GENE
+or	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+/	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+related	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+.	O
+
+During	O
+the	O
+aftermath	O
+of	O
+excitation	O
+of	O
+the	O
+skin	O
+sympathetic	O
+nerve	O
+by	O
+mental	O
+arithmetics	O
+,	O
+3	O
+/	O
+12	O
+A	O
+delta	O
+units	O
+were	O
+turned	O
+to	O
+the	O
+active	O
+state	O
+with	O
+decreased	O
+mechanical	O
+threshold	O
+.	O
+
+In	O
+a	O
+similar	O
+fashion	O
+to	O
+adipose	O
+stromal	O
+cells	O
+,	O
+serum	O
+potentiated	O
+the	O
+response	O
+to	O
+dexamethasone	O
+but	O
+had	O
+no	O
+effect	O
+on	O
+phorbol	O
+ester	O
+-	O
+stimulated	O
+activity	O
+.	O
+
+Thus	O
+,	O
+Hex	B-GENE
+expression	O
+marks	O
+the	O
+earliest	O
+unequivocal	O
+molecular	O
+anteroposterior	O
+asymmetry	O
+in	O
+the	O
+mouse	O
+embryo	O
+and	O
+indicates	O
+that	O
+the	O
+anteroposterior	O
+axis	O
+of	O
+the	O
+embryo	O
+develops	O
+from	O
+conversion	O
+of	O
+a	O
+proximodistal	O
+asymmetry	O
+established	O
+in	O
+the	O
+primitive	O
+endoderm	O
+lineage	O
+.	O
+
+CONCLUSIONS	O
+:	O
+While	O
+INR	O
+correction	O
+may	O
+be	O
+achieved	O
+by	O
+all	O
+the	O
+above	O
+methods	O
+,	O
+that	O
+relating	O
+log	O
+reference	O
+INR	O
+to	O
+log	O
+local	O
+prothrombin	B-GENE
+time	O
+by	O
+linear	O
+regression	O
+analysis	O
+is	O
+the	O
+simplest	O
+to	O
+perform	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+overall	O
+FNF	O
+for	O
+1992	O
+was	O
+12	O
+.	O
+3	O
+%	O
+and	O
+was	O
+19	O
+.	O
+1	O
+%	O
+,	O
+22	O
+.	O
+2	O
+%	O
+,	O
+3	O
+.	O
+8	O
+%	O
+and	O
+6	O
+.	O
+1	O
+%	O
+per	O
+successive	O
+quarters	O
+in	O
+1992	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+of	O
+various	O
+bovine	O
+tissues	O
+with	O
+human	O
+NMT	B-GENE
+peptide	I-GENE
+antibody	I-GENE
+indicated	O
+a	O
+common	O
+prominent	O
+immunoreactive	O
+band	O
+with	O
+an	O
+apparent	O
+molecular	O
+mass	O
+of	O
+48	O
+.	O
+5	O
+-	O
+50	O
+kDa	O
+in	O
+all	O
+tissues	O
+.	O
+
+Transcription	O
+start	O
+sites	O
+of	O
+the	O
+plastid	O
+ACCase	B-GENE
+genes	I-GENE
+were	O
+estimated	O
+from	O
+the	O
+longest	O
+cDNA	O
+clones	O
+obtained	O
+by	O
+5	O
+'	O
+-	O
+RACE	O
+(	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+)	O
+.	O
+
+AIDS	O
+-	O
+related	O
+disseminated	O
+histoplasmosis	O
+in	O
+San	O
+Francisco	O
+,	O
+California	O
+.	O
+
+Thus	O
+,	O
+Fis	B-GENE
+acts	O
+as	O
+an	O
+accessory	O
+transcriptional	O
+activator	O
+at	O
+the	O
+mar	B-GENE
+promoter	I-GENE
+.	O
+
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+exposure	O
+markedly	O
+increased	O
+activity	O
+of	O
+several	O
+RNA	O
+-	O
+binding	O
+proteins	O
+,	O
+especially	O
+a	O
+novel	O
+Mr	O
+50	O
+,	O
+000	O
+-	O
+55	O
+,	O
+000	O
+RNA	O
+-	O
+binding	O
+protein	O
+.	O
+
+We	O
+speculate	O
+that	O
+the	O
+human	O
+papillomavirus	O
+late	O
+mRNAs	O
+,	O
+produced	O
+from	O
+several	O
+hundred	O
+copies	O
+of	O
+the	O
+virus	O
+genome	O
+present	O
+in	O
+infected	O
+cells	O
+,	O
+compete	O
+with	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+mRNAs	I-GENE
+for	O
+destabilizing	O
+cellular	O
+factors	O
+and	O
+that	O
+this	O
+may	O
+lead	O
+to	O
+elevated	O
+Fos	B-GENE
+protein	I-GENE
+levels	O
+in	O
+human	O
+papillomavirus	O
+infected	O
+cells	O
+.	O
+
+Two	O
+closely	O
+related	O
+IgH	B-GENE
+constant	O
+region	O
+genes	O
+,	O
+CHA	B-GENE
+and	O
+CHB	B-GENE
+,	O
+have	O
+been	O
+sequenced	O
+completely	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+find	O
+out	O
+whether	O
+it	O
+was	O
+possible	O
+to	O
+detect	O
+normal	O
+lymph	O
+nodes	O
+by	O
+high	O
+-	O
+resolution	O
+mediastinal	O
+US	O
+.	O
+
+To	O
+study	O
+the	O
+role	O
+of	O
+heavy	O
+chain	O
+motifs	O
+in	O
+substrate	O
+recognition	O
+,	O
+secreted	O
+variants	O
+of	O
+recombinant	B-GENE
+bovine	I-GENE
+proenteropeptidase	I-GENE
+were	O
+constructed	O
+by	O
+replacing	O
+the	O
+transmembrane	O
+domain	O
+with	O
+a	O
+signal	O
+peptide	O
+.	O
+
+CKbeta4GT	B-GENE
+-	I-GENE
+II	I-GENE
+is	O
+predicted	O
+to	O
+encode	O
+a	O
+type	B-GENE
+II	I-GENE
+transmembrane	I-GENE
+glycoprotein	I-GENE
+of	O
+43	O
+kDa	O
+with	O
+five	O
+potential	O
+N	O
+-	O
+linked	O
+glycosylation	O
+sites	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Semen	O
+analyses	O
+were	O
+performed	O
+on	O
+58	O
+patients	O
+with	O
+stages	O
+I	O
+-	O
+III	O
+HD	O
+before	O
+,	O
+during	O
+,	O
+and	O
+after	O
+chemotherapy	O
+and	O
+after	O
+the	O
+sperm	O
+count	O
+recovered	O
+from	O
+the	O
+effects	O
+of	O
+abdominal	O
+radiotherapy	O
+that	O
+was	O
+given	O
+after	O
+chemotherapy	O
+.	O
+
+Thus	O
+,	O
+the	O
+absence	O
+of	O
+residual	O
+infarct	O
+-	O
+zone	O
+viability	O
+discriminates	O
+patients	O
+who	O
+develop	O
+progressive	O
+left	O
+ventricular	O
+dilation	O
+after	O
+reperfused	O
+AMI	O
+from	O
+those	O
+who	O
+maintain	O
+normal	O
+left	O
+ventricular	O
+geometry	O
+.	O
+
+With	O
+a	O
+BMI	O
+cutoff	O
+of	O
+27	O
+,	O
+mean	O
+cardiac	O
+NE	O
+spillover	O
+was	O
+46	O
+%	O
+lower	O
+in	O
+the	O
+obese	O
+subjects	O
+when	O
+compared	O
+with	O
+the	O
+lean	O
+subjects	O
+(	O
+P	O
+=	O
+.	O
+017	O
+)	O
+.	O
+
+The	O
+gene	O
+(	O
+ApxII	B-GENE
+)	O
+encoding	O
+both	O
+chloroplastic	B-GENE
+ascorbate	I-GENE
+peroxidase	I-GENE
+isoenzymes	I-GENE
+was	O
+isolated	O
+and	O
+the	O
+organization	O
+of	O
+the	O
+gene	O
+was	O
+determined	O
+.	O
+
+This	O
+emphasizes	O
+the	O
+conclusion	O
+that	O
+CDF	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+not	O
+an	O
+E2F	B-GENE
+family	I-GENE
+member	I-GENE
+and	O
+points	O
+to	O
+profound	O
+differences	O
+in	O
+the	O
+cell	O
+cycle	O
+regulation	O
+of	O
+CDF	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+E2F	B-GENE
+.	O
+
+The	O
+proofreading	O
+domain	O
+of	O
+Escherichia	B-GENE
+coli	I-GENE
+DNA	I-GENE
+polymerase	I-GENE
+I	I-GENE
+and	O
+other	O
+DNA	B-GENE
+and	I-GENE
+/	I-GENE
+or	I-GENE
+RNA	I-GENE
+exonuclease	I-GENE
+domains	I-GENE
+.	O
+
+Responsibility	O
+matters	O
+-	O
+-	O
+this	O
+is	O
+a	O
+scientific	O
+council	O
+
+Sequences	O
+required	O
+for	O
+interaction	O
+of	O
+mu2	B-GENE
+and	O
+CTLA	B-GENE
+-	I-GENE
+4	I-GENE
+were	O
+localized	O
+to	O
+residues	O
+,	O
+161TTGVY	O
+in	O
+CTLA	B-GENE
+-	I-GENE
+4	I-GENE
+;	O
+this	O
+sequence	O
+is	O
+N	O
+-	O
+terminal	O
+to	O
+,	O
+but	O
+overlaps	O
+with	O
+,	O
+a	O
+previously	O
+identified	O
+SH2	B-GENE
+binding	I-GENE
+motif	I-GENE
+,	O
+165YVKM	O
+,	O
+involved	O
+in	O
+CTLA	B-GENE
+-	I-GENE
+4	I-GENE
+signaling	O
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+that	O
+a	O
+transfected	O
+Chinese	O
+hamster	O
+ovary	O
+(	O
+CHO	O
+)	O
+cell	O
+line	O
+expressing	O
+a	O
+murine	B-GENE
+CD4	I-GENE
+fragment	I-GENE
+containing	O
+the	O
+first	O
+two	O
+N	O
+-	O
+terminal	O
+domains	O
+secretes	O
+both	O
+monomeric	O
+molecules	O
+and	O
+disulfide	O
+-	O
+linked	O
+multimers	O
+.	O
+
+Coexpression	O
+of	O
+mouse	O
+PKR	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+515	I-GENE
+)	I-GENE
+WT	I-GENE
+as	O
+a	O
+Gal4	B-GENE
+DNA	O
+-	O
+binding	O
+domain	O
+fusion	O
+with	O
+either	O
+the	O
+catalytic	O
+-	O
+deficient	O
+human	O
+PKR	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+551	I-GENE
+)	I-GENE
+K296R	O
+mutant	O
+,	O
+the	O
+RNA	O
+-	O
+binding	O
+-	O
+deficient	O
+human	O
+PKR	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+551	I-GENE
+)	I-GENE
+K64E	I-GENE
+/	I-GENE
+K296R	I-GENE
+double	O
+mutant	O
+,	O
+or	O
+wild	O
+-	O
+type	O
+mouse	O
+PKR	B-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+515	I-GENE
+)	I-GENE
+WT	I-GENE
+as	O
+full	O
+-	O
+length	O
+PKR	B-GENE
+-	O
+Gal4	B-GENE
+activation	O
+domain	O
+fusions	O
+resulted	O
+in	O
+activation	O
+of	O
+the	O
+HIS3	B-GENE
+and	O
+lacZ	B-GENE
+reporters	O
+.	O
+
+Using	O
+GST	B-GENE
+-	O
+PKR	B-GENE
+fusion	O
+chromatography	O
+,	O
+direct	O
+physical	O
+interaction	O
+between	O
+the	O
+mouse	O
+and	O
+human	B-GENE
+PKR	I-GENE
+homologs	I-GENE
+was	O
+established	O
+.	O
+
+An	O
+even	O
+greater	O
+inflammatory	O
+response	O
+was	O
+observed	O
+after	O
+intratracheal	O
+instillation	O
+of	O
+ufCB	O
+,	O
+but	O
+not	O
+after	O
+CB	O
+instillation	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+avirulent	O
+strain	O
+H37Ra	O
+showed	O
+weak	O
+hybridization	O
+with	O
+these	O
+two	O
+probes	O
+,	O
+suggesting	O
+that	O
+these	O
+genes	O
+might	O
+have	O
+been	O
+deleted	O
+in	O
+the	O
+avirulent	O
+strain	O
+or	O
+are	O
+present	O
+in	O
+limited	O
+copy	O
+numbers	O
+as	O
+opposed	O
+to	O
+those	O
+in	O
+the	O
+virulent	O
+strain	O
+H37Rv	O
+.	O
+
+These	O
+defects	O
+no	O
+doubt	O
+impair	O
+the	O
+folding	O
+and	O
+configuration	O
+necessary	O
+for	O
+normal	O
+processing	O
+of	O
+the	O
+AVP	B-GENE
+gene	I-GENE
+precursor	I-GENE
+.	O
+
+Similarities	O
+between	O
+the	O
+hIGFBP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+phosphoenolpyruvate	B-GENE
+kinase	I-GENE
+(	O
+PEPCK	B-GENE
+)	O
+promoters	O
+,	O
+including	O
+regions	O
+conferring	O
+insulin	B-GENE
+,	O
+glucocorticoid	O
+,	O
+and	O
+cyclic	O
+adenosine	O
+-	O
+monophosphate	O
+responses	O
+,	O
+are	O
+consistent	O
+with	O
+our	O
+previous	O
+hypothesis	O
+that	O
+IGFBP	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+involved	O
+in	O
+regulation	O
+of	O
+glucose	O
+metabolism	O
+.	O
+
+This	O
+binary	O
+repeat	O
+contains	O
+repetitive	O
+DNA	O
+elements	O
+that	O
+include	O
+LINES	O
+,	O
+SINES	O
+,	O
+medium	O
+reiteration	O
+frequency	O
+repeats	O
+,	O
+and	O
+a	O
+transposon	O
+-	O
+like	O
+element	O
+.	O
+
+At	O
+60	O
+days	O
+the	O
+amount	O
+of	O
+gangliosides	O
+was	O
+on	O
+average	O
+lower	O
+in	O
+females	O
+than	O
+in	O
+males	O
+,	O
+even	O
+if	O
+with	O
+some	O
+exception	O
+.	O
+
+Large	O
+genomic	O
+constructs	O
+integrate	O
+at	O
+the	O
+endogenous	O
+locus	O
+by	O
+homologous	O
+recombination	O
+,	O
+but	O
+cDNA	O
+-	O
+derived	O
+sequences	O
+lacking	O
+long	O
+stretches	O
+of	O
+contiguous	O
+genomic	O
+DNA	O
+(	O
+due	O
+to	O
+intron	O
+excision	O
+)	O
+typically	O
+integrate	O
+into	O
+chromosomal	O
+DNA	O
+by	O
+nonhomologous	O
+recombination	O
+.	O
+
+During	O
+the	O
+conditioning	O
+procedure	O
+,	O
+the	O
+C	O
+-	O
+fiber	O
+reflex	O
+was	O
+facilitated	O
+(	O
+wind	O
+-	O
+up	O
+)	O
+in	O
+a	O
+stimulus	O
+-	O
+dependent	O
+fashion	O
+in	O
+intact	O
+,	O
+anesthetized	O
+animals	O
+during	O
+the	O
+application	O
+of	O
+the	O
+first	O
+seven	O
+conditioning	O
+stimuli	O
+;	O
+thereafter	O
+,	O
+the	O
+magnitude	O
+of	O
+the	O
+responses	O
+reached	O
+a	O
+plateau	O
+and	O
+then	O
+decreased	O
+.	O
+
+As	O
+a	O
+sequence	O
+-	O
+specific	O
+DNA	O
+binding	O
+transcription	O
+factor	O
+,	O
+p53	B-GENE
+specifically	O
+binds	O
+to	O
+a	O
+20	O
+-	O
+bp	O
+consensus	O
+motif	O
+5	O
+'	O
+-	O
+PuPuPuC	O
+(	O
+A	O
+/	O
+T	O
+)	O
+(	O
+T	O
+/	O
+A	O
+)	O
+GPyPyPyPuPuPuC	O
+(	O
+A	O
+/	O
+T	O
+)	O
+(	O
+T	O
+/	O
+A	O
+)	O
+GPyPyPy	O
+-	O
+3	O
+'	O
+.	O
+
+Upon	O
+UV	O
+damage	O
+,	O
+Crb2	B-GENE
+is	O
+transiently	O
+modified	O
+,	O
+probably	O
+phosphorylated	O
+,	O
+with	O
+a	O
+similar	O
+timing	O
+of	O
+phosphorylation	O
+in	O
+Chk1	B-GENE
+kinase	I-GENE
+,	O
+which	O
+is	O
+reported	O
+to	O
+restrain	O
+Cdc2	B-GENE
+activation	O
+.	O
+
+Moreover	O
+,	O
+moderate	O
+overexpression	O
+of	O
+Chk1	B-GENE
+suppresses	O
+the	O
+phenotypes	O
+of	O
+cut5	B-GENE
+and	O
+crb2	B-GENE
+mutants	I-GENE
+.	O
+
+Tcn1p	B-GENE
+/	O
+Crz1p	B-GENE
+,	O
+a	O
+calcineurin	O
+-	O
+dependent	O
+transcription	O
+factor	O
+that	O
+differentially	O
+regulates	O
+gene	O
+expression	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Structure	O
+and	O
+localization	O
+of	O
+the	O
+human	O
+gene	O
+encoding	O
+SR	B-GENE
+-	I-GENE
+BI	I-GENE
+/	O
+CLA	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+We	O
+introduced	O
+the	O
+gel	O
+technique	O
+as	O
+a	O
+routine	O
+assay	O
+for	O
+antibody	O
+detection	O
+and	O
+identification	O
+in	O
+1993	O
+.	O
+
+Stability	O
+of	O
+pyrimethamine	O
+in	O
+a	O
+liquid	O
+dosage	O
+formulation	O
+stored	O
+for	O
+three	O
+months	O
+.	O
+
+Multiple	O
+regression	O
+analyses	O
+revealed	O
+that	O
+WAIS	O
+-	O
+R	O
+factor	O
+scores	O
+Verbal	O
+Comprehension	O
+and	O
+Freedom	O
+from	O
+Distractibility	O
+accounted	O
+for	O
+up	O
+to	O
+42	O
+%	O
+of	O
+the	O
+variance	O
+in	O
+WMS	O
+-	O
+R	O
+and	O
+CVLT	O
+indices	O
+.	O
+
+Bilateral	O
+basal	O
+arteries	O
+were	O
+measured	O
+by	O
+the	O
+transtemporal	O
+approach	O
+with	O
+a	O
+2	O
+MHz	O
+pulsed	O
+Doppler	O
+instrument	O
+(	O
+TC	O
+-	O
+2	O
+64B	O
+EME	O
+)	O
+.	O
+
+At	O
+the	O
+genomic	O
+level	O
+,	O
+the	O
+sequences	O
+of	O
+two	O
+members	O
+of	O
+this	O
+family	O
+are	O
+known	O
+in	O
+the	O
+rat	O
+Rattus	O
+norvegicus	O
+:	O
+the	O
+VCSA1	B-GENE
+gene	I-GENE
+,	O
+encoding	O
+the	O
+prohormone	B-GENE
+-	I-GENE
+like	I-GENE
+polypeptide	I-GENE
+SMR1	I-GENE
+,	O
+and	O
+the	O
+VCSB1	B-GENE
+gene	I-GENE
+,	O
+encoding	O
+a	O
+salivary	O
+Pro	O
+-	O
+rich	O
+polypeptide	O
+.	O
+
+The	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+RAD30	I-GENE
+gene	I-GENE
+,	O
+a	O
+homologue	B-GENE
+of	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+dinB	I-GENE
+and	O
+umuC	B-GENE
+,	O
+is	O
+DNA	O
+damage	O
+inducible	O
+and	O
+functions	O
+in	O
+a	O
+novel	O
+error	O
+-	O
+free	O
+postreplication	O
+repair	O
+mechanism	O
+.	O
+
+However	O
+,	O
+in	O
+a	O
+new	O
+experiment	O
+in	O
+which	O
+the	O
+deletion	O
+task	O
+was	O
+presented	O
+as	O
+a	O
+puppet	O
+game	O
+,	O
+and	O
+with	O
+pretraining	O
+and	O
+selection	O
+on	O
+vowel	O
+deletion	O
+,	O
+a	O
+significantly	O
+higher	O
+level	O
+of	O
+success	O
+was	O
+achieved	O
+by	O
+the	O
+children	O
+working	O
+with	O
+the	O
+CVCC	O
+material	O
+.	O
+
+Diet	O
+therapy	O
+with	O
+soy	O
+proteins	O
+for	O
+chronic	O
+stomach	O
+ulcers	O
+
+In	O
+ICU	O
+patients	O
+,	O
+the	O
+LIS	O
+related	O
+to	O
+the	O
+postoperative	O
+rise	O
+in	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+level	O
+only	O
+,	O
+even	O
+though	O
+the	O
+rise	O
+in	O
+plasma	O
+concentrations	O
+of	O
+cytokines	O
+interrelated	O
+.	O
+
+Resistance	O
+training	O
+shifts	O
+the	O
+power	O
+curve	O
+in	O
+a	O
+positive	O
+direction	O
+when	O
+the	O
+measurements	O
+are	O
+determined	O
+with	O
+absolute	O
+loads	O
+,	O
+but	O
+the	O
+increased	O
+power	O
+may	O
+not	O
+be	O
+transferred	O
+to	O
+an	O
+absolute	O
+performance	O
+task	O
+like	O
+the	O
+SSP	O
+.	O
+
+Gel	O
+-	O
+shift	O
+assays	O
+identified	O
+two	O
+Sp1	B-GENE
+binding	I-GENE
+sites	I-GENE
+within	O
+this	O
+element	O
+.	O
+
+Gel	O
+mobility	O
+shift	O
+and	O
+super	O
+-	O
+shift	O
+assays	O
+using	O
+liver	O
+nuclear	O
+extracts	O
+from	O
+either	O
+rat	O
+liver	O
+or	O
+DDT1MF	O
+-	O
+2	O
+cells	O
+demonstrated	O
+that	O
+the	O
+CRE	O
+in	O
+the	O
+alpha	B-GENE
+1B	I-GENE
+-	I-GENE
+AR	I-GENE
+gene	I-GENE
+bound	O
+CRE	B-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+,	O
+in	O
+this	O
+experimental	O
+model	O
+,	O
+ACE	B-GENE
+inhibitors	O
+limit	O
+the	O
+arrhythmias	O
+following	O
+ischemia	O
+-	O
+reperfusion	O
+and	O
+free	O
+radical	O
+scavenging	O
+action	O
+of	O
+these	O
+drugs	O
+does	O
+not	O
+have	O
+a	O
+major	O
+contributory	O
+role	O
+in	O
+their	O
+protective	O
+effect	O
+.	O
+
+The	O
+murine	O
+Htf9	B-GENE
+-	I-GENE
+a	I-GENE
+/	O
+RanBP1	B-GENE
+and	O
+Htf9	B-GENE
+-	I-GENE
+c	I-GENE
+genes	I-GENE
+are	O
+divergently	O
+transcribed	O
+from	O
+a	O
+shared	O
+TATA	O
+-	O
+less	O
+promoter	O
+.	O
+
+In	O
+accordance	O
+with	O
+clinical	O
+improvement	O
+we	O
+found	O
+a	O
+decrease	O
+of	O
+laboratory	O
+indicators	O
+of	O
+inflammation	O
+(	O
+C	B-GENE
+-	I-GENE
+reactive	I-GENE
+protein	I-GENE
+,	O
+alpha	B-GENE
+2	I-GENE
+-	I-GENE
+globuline	I-GENE
+,	O
+prostaglandin	O
+E2	O
+)	O
+.	O
+
+We	O
+have	O
+previously	O
+reported	O
+that	O
+depletion	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+by	O
+long	O
+-	O
+term	O
+treatment	O
+of	O
+B16	O
+mouse	O
+melanoma	O
+cells	O
+with	O
+phorbol	O
+dibutyrate	O
+(	O
+PDBu	O
+)	O
+prevented	O
+cell	O
+density	O
+-	O
+dependent	O
+melanogenesis	O
+.	O
+
+Replacement	O
+of	O
+residues	O
+in	O
+positions	O
++	O
+3	O
+(	O
+His128Asn	O
+)	O
+and	O
++	O
+2	O
+(	O
+Gln155Lys	O
+)	O
+of	O
+the	O
+reading	O
+helices	O
+of	O
+fingers	O
+2	O
+and	O
+3	O
+,	O
+respectively	O
+,	O
+prevented	O
+binding	O
+.	O
+
+Two	O
+disulphide	O
+bridges	O
+,	O
+which	O
+are	O
+conserved	O
+in	O
+all	O
+spermadhesin	O
+molecules	O
+and	O
+many	O
+CUB	O
+domains	O
+,	O
+crosslink	O
+loop	O
+LA	O
+and	O
+strand	O
+beta	O
+4	O
+and	O
+loops	O
+LE	O
+and	O
+LG	O
+,	O
+respectively	O
+,	O
+at	O
+opposite	O
+edges	O
+of	O
+the	O
+same	O
+face	O
+of	O
+the	O
+domain	O
+.	O
+
+Mg	B-GENE
+-	I-GENE
+chelatase	I-GENE
+of	O
+tobacco	O
+:	O
+identification	O
+of	O
+a	O
+Chl	B-GENE
+D	I-GENE
+cDNA	I-GENE
+sequence	I-GENE
+encoding	O
+a	O
+third	O
+subunit	O
+,	O
+analysis	O
+of	O
+the	O
+interaction	O
+of	O
+the	O
+three	O
+subunits	O
+with	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+,	O
+and	O
+reconstitution	O
+of	O
+the	O
+enzyme	O
+activity	O
+by	O
+co	O
+-	O
+expression	O
+of	O
+recombinant	B-GENE
+CHL	I-GENE
+D	I-GENE
+,	O
+CHL	B-GENE
+H	I-GENE
+and	O
+CHL	B-GENE
+I	I-GENE
+.	O
+
+One	O
+R	O
+-	O
+EST	O
+and	O
+one	O
+Pto	B-GENE
+-	I-GENE
+like	I-GENE
+sequence	I-GENE
+each	O
+mapped	O
+to	O
+two	O
+locations	O
+.	O
+
+The	O
+multidomain	O
+structure	O
+includes	O
+a	O
+cysteine	O
+-	O
+rich	O
+motif	O
+resembling	O
+those	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+and	O
+n	B-GENE
+-	I-GENE
+chimaerin	I-GENE
+and	O
+a	O
+putative	O
+pleckstrin	B-GENE
+homology	I-GENE
+domain	I-GENE
+.	O
+
+271	O
+:	O
+31290	O
+-	O
+31295	O
+,	O
+1996	O
+)	O
+.	O
+
+Nevertheless	O
+,	O
+antibodies	O
+directed	O
+against	O
+an	O
+epitope	O
+-	O
+tagged	O
+version	O
+of	O
+Prp42p	B-GENE
+specifically	O
+precipitate	O
+U1	B-GENE
+snRNA	I-GENE
+from	O
+yeast	O
+extracts	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+in	O
+addition	O
+to	O
+Grb2	B-GENE
+-	O
+mediated	O
+activation	O
+of	O
+Ras	B-GENE
+,	O
+PLC	B-GENE
+-	I-GENE
+gamma1	I-GENE
+-	O
+mediated	O
+DAG	O
+production	O
+is	O
+required	O
+for	O
+EGF	B-GENE
+-	O
+and	O
+PDGF	B-GENE
+-	O
+induced	O
+S	O
+-	O
+phase	O
+entry	O
+and	O
+gene	O
+expression	O
+,	O
+possibly	O
+through	O
+activation	O
+of	O
+PKC	B-GENE
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+investigated	O
+STAT	B-GENE
+activation	O
+in	O
+a	O
+panel	O
+of	O
+rodent	O
+fibroblast	O
+cell	O
+lines	O
+stably	O
+transformed	O
+by	O
+diverse	O
+viral	O
+oncoproteins	O
+.	O
+
+In	O
+serum	O
+-	O
+stimulated	O
+cells	O
+,	O
+the	O
+binding	O
+of	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+/	O
+CBF	B-GENE
+to	O
+TKC1	B-GENE
+increased	O
+gradually	O
+,	O
+reaching	O
+a	O
+plateau	O
+at	O
+the	O
+S	O
+phase	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+our	O
+animal	O
+model	O
+,	O
+blood	O
+-	O
+brain	O
+barrier	O
+disruption	O
+was	O
+a	O
+reproducible	O
+,	O
+integral	O
+finding	O
+of	O
+single	O
+-	O
+fraction	O
+,	O
+high	O
+-	O
+dose	O
+irradiation	O
+injury	O
+.	O
+
+To	O
+facilitate	O
+the	O
+investigation	O
+of	O
+parameters	O
+that	O
+govern	O
+selective	O
+export	O
+in	O
+adenovirus	O
+-	O
+infected	O
+cells	O
+,	O
+we	O
+constructed	O
+a	O
+marked	O
+human	O
+beta	B-GENE
+-	I-GENE
+actin	I-GENE
+minigene	I-GENE
+under	O
+the	O
+control	O
+of	O
+the	O
+glucocorticoid	B-GENE
+-	I-GENE
+inducible	I-GENE
+enhancer	I-GENE
+-	I-GENE
+promoter	I-GENE
+of	O
+mouse	O
+mammary	O
+tumor	O
+virus	O
+and	O
+introduced	O
+it	O
+into	O
+the	O
+left	O
+end	O
+of	O
+the	O
+adenovirus	O
+type	O
+5	O
+(	O
+Ad5	O
+)	O
+genome	O
+.	O
+
+Cell	O
+factor	O
+-	O
+mediated	O
+regulatory	O
+interactions	O
+are	O
+involved	O
+in	O
+regulating	O
+the	O
+restricted	O
+expression	O
+of	O
+the	O
+HCMV	B-GENE
+major	I-GENE
+immediate	I-GENE
+-	I-GENE
+early	I-GENE
+(	I-GENE
+IE	I-GENE
+)	I-GENE
+gene	I-GENE
+(	O
+J	O
+.	O
+
+MpB	B-GENE
+GroEL	I-GENE
+has	O
+extensive	O
+sequence	O
+similarity	O
+(	O
+92	O
+%	O
+)	O
+with	O
+Escherichia	B-GENE
+coli	I-GENE
+GroEL	I-GENE
+and	O
+other	O
+members	O
+of	O
+the	O
+chaperonin	B-GENE
+-	I-GENE
+60	I-GENE
+family	I-GENE
+.	O
+
+The	O
+critical	O
+mutations	O
+were	O
+likely	O
+to	O
+have	O
+been	O
+multiple	O
+and	O
+dispersed	O
+,	O
+including	O
+elongation	O
+of	O
+the	O
+TM	O
+and	O
+Nef	B-GENE
+coding	I-GENE
+sequences	I-GENE
+;	O
+changes	O
+in	O
+RNA	O
+splice	O
+donor	O
+and	O
+acceptor	O
+sites	O
+,	O
+TATA	O
+box	O
+sites	O
+,	O
+and	O
+Sp1	B-GENE
+sites	I-GENE
+;	O
+multiple	O
+changes	O
+in	O
+the	O
+V2	B-GENE
+region	O
+of	O
+SU	B-GENE
+,	O
+including	O
+a	O
+consensus	O
+neutralization	O
+epitope	O
+;	O
+and	O
+five	O
+new	O
+N	O
+-	O
+linked	O
+glycosylation	O
+sites	O
+in	O
+SU	B-GENE
+.	O
+
+C	O
+.	O
+
+These	O
+are	O
+the	O
+long	O
+terminal	O
+repeat	O
+(	O
+LTR	O
+)	O
+promoter	O
+,	O
+which	O
+regulates	O
+expression	O
+of	O
+the	O
+viral	O
+structural	O
+proteins	O
+,	O
+and	O
+a	O
+second	O
+internal	O
+promoter	O
+,	O
+located	O
+towards	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+env	B-GENE
+gene	I-GENE
+,	O
+that	O
+directs	O
+expression	O
+of	O
+the	O
+viral	O
+auxiliary	O
+proteins	O
+.	O
+
+The	O
+5	O
+'	O
+end	O
+of	O
+the	O
+genomic	O
+RNA	O
+of	O
+rubella	O
+virus	O
+(	O
+RUB	O
+)	O
+contains	O
+a	O
+14	O
+-	O
+nucleotide	O
+(	O
+nt	O
+)	O
+single	O
+-	O
+stranded	O
+leader	O
+(	O
+ss	O
+-	O
+leader	O
+)	O
+followed	O
+by	O
+a	O
+stem	O
+-	O
+and	O
+-	O
+loop	O
+structure	O
+[	O
+5	O
+'	O
+(	O
++	O
+)	O
+SL	O
+]	O
+(	O
+nt	O
+15	O
+to	O
+65	O
+)	O
+,	O
+the	O
+complement	O
+of	O
+which	O
+at	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+minus	O
+-	O
+strand	O
+RNA	O
+[	O
+3	O
+'	O
+(	O
+-	O
+)	O
+SL	O
+]	O
+has	O
+been	O
+proposed	O
+to	O
+function	O
+as	O
+a	O
+promoter	O
+for	O
+synthesis	O
+of	O
+genomic	O
+plus	O
+strands	O
+.	O
+
+To	O
+investigate	O
+the	O
+requirements	O
+for	O
+CBF2	B-GENE
+binding	O
+,	O
+we	O
+synthesized	O
+a	O
+series	O
+of	O
+oligonucleotides	O
+carrying	O
+double	O
+transversion	O
+mutations	O
+spanning	O
+both	O
+the	O
+conserved	O
+core	O
+sequence	O
+and	O
+outside	O
+flanking	O
+sequences	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+affinities	O
+of	O
+CBF2	B-GENE
+for	O
+binding	O
+to	O
+the	O
+LMP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+LMP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+and	O
+CD23	B-GENE
+promoters	I-GENE
+were	O
+also	O
+measured	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+myocardial	O
+uptake	O
+of	O
+99mTc	O
+sestamibi	O
+in	O
+normal	O
+subjects	O
+and	O
+patients	O
+with	O
+coronary	O
+artery	O
+disease	O
+is	O
+comparable	O
+after	O
+exercise	O
+,	O
+dipyridamole	O
+,	O
+and	O
+adenosine	O
+stress	O
+.	O
+
+The	O
+SR	B-GENE
+protein	I-GENE
+family	I-GENE
+is	O
+involved	O
+in	O
+constitutive	O
+and	O
+regulated	O
+pre	O
+-	O
+mRNA	O
+splicing	O
+and	O
+has	O
+been	O
+found	O
+to	O
+be	O
+evolutionarily	O
+conserved	O
+in	O
+metazoan	O
+organisms	O
+.	O
+
+To	O
+investigate	O
+the	O
+activity	O
+of	O
+TCF11	B-GENE
+through	O
+this	O
+selected	O
+site	O
+,	O
+both	O
+alone	O
+and	O
+in	O
+the	O
+presence	O
+of	O
+MafG	B-GENE
+,	O
+we	O
+have	O
+used	O
+a	O
+transient	O
+transfection	O
+assay	O
+.	O
+
+These	O
+and	O
+other	O
+comparisons	O
+suggest	O
+that	O
+,	O
+during	O
+evolution	O
+,	O
+both	O
+the	O
+RNA	B-GENE
+-	I-GENE
+polymerase	I-GENE
+specificity	O
+of	O
+telomerase	B-GENE
+RNA	I-GENE
+-	I-GENE
+gene	I-GENE
+promoters	I-GENE
+and	O
+,	O
+more	O
+recently	O
+,	O
+the	O
+position	O
+of	O
+the	O
+template	O
+sequence	O
+in	O
+the	O
+telomerase	B-GENE
+RNA	I-GENE
+changed	O
+.	O
+
+Deadenylation	O
+and	O
+decay	O
+of	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+mRNA	I-GENE
+in	O
+K562	O
+cells	O
+is	O
+extraordinarily	O
+slow	O
+compared	O
+with	O
+NIH	O
+3T3	O
+cells	O
+,	O
+suggesting	O
+that	O
+the	O
+increased	O
+stability	O
+gained	O
+by	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+mRNA	I-GENE
+in	O
+K562	O
+cells	O
+is	O
+mainly	O
+controlled	O
+at	O
+the	O
+deadenylation	O
+step	O
+.	O
+
+Holliday	B-GENE
+junction	I-GENE
+resolvase	I-GENE
+in	O
+Schizosaccharomyces	O
+pombe	O
+has	O
+identical	O
+endonuclease	O
+activity	O
+to	O
+the	O
+CCE1	B-GENE
+homologue	O
+YDC2	B-GENE
+.	O
+
+Ca2	B-GENE
++	I-GENE
+/	I-GENE
+calmodulin	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+II	I-GENE
+(	O
+CaMK	B-GENE
+II	I-GENE
+)	O
+is	O
+a	O
+multifunctional	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+protein	I-GENE
+kinase	I-GENE
+that	O
+regulates	O
+ion	O
+channels	O
+,	O
+metabolic	O
+enzymes	O
+,	O
+cytoskeletal	O
+proteins	O
+,	O
+and	O
+possibly	O
+transcription	O
+factors	O
+.	O
+
+A	O
+cAMP	O
+-	O
+responsive	O
+element	O
+-	O
+like	O
+(	O
+CRE	O
+-	O
+like	O
+,	O
+TGACGTGA	O
+)	O
+promoter	O
+sequence	O
+and	O
+a	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+signaling	O
+pathway	O
+are	O
+involved	O
+in	O
+this	O
+induction	O
+,	O
+and	O
+activation	O
+of	O
+both	O
+CRE	B-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+CREB	B-GENE
+)	O
+and	O
+activating	B-GENE
+transcription	I-GENE
+factor	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+ATF	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+is	O
+required	O
+in	O
+the	O
+above	O
+process	O
+.	O
+
+IVOX	O
+was	O
+named	O
+as	O
+an	O
+acronym	O
+for	O
+intravascular	O
+oxygenator	O
+.	O
+
+Histopathologically	O
+,	O
+a	O
+cystic	O
+lymphangioma	O
+was	O
+diagnosed	O
+because	O
+of	O
+the	O
+morphological	O
+features	O
+and	O
+the	O
+immunohistochemical	O
+stainings	O
+of	O
+CD34	B-GENE
+and	O
+Factor	B-GENE
+VIII	I-GENE
+related	I-GENE
+antigen	I-GENE
+which	O
+were	O
+observed	O
+positive	O
+reactions	O
+in	O
+endothelial	O
+cells	O
+of	O
+the	O
+cysts	O
+.	O
+
+Protease	O
+activities	O
+in	O
+cultures	O
+of	O
+the	O
+streptococcal	O
+strains	O
+were	O
+associated	O
+with	O
+species	O
+of	O
+different	O
+molecular	O
+masses	O
+ranging	O
+from	O
+130	O
+to	O
+200	O
+kDa	O
+,	O
+suggesting	O
+posttranslational	O
+processing	O
+possibly	O
+as	O
+a	O
+result	O
+of	O
+autoproteolysis	O
+at	O
+post	O
+-	O
+proline	O
+peptide	O
+bonds	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+parts	O
+of	O
+the	O
+molecules	O
+.	O
+
+The	O
+mechanism	O
+underlying	O
+such	O
+analgesia	O
+has	O
+been	O
+suggested	O
+to	O
+involve	O
+the	O
+interaction	O
+between	O
+the	O
+two	O
+separate	O
+but	O
+interconnected	O
+motivational	O
+systems	O
+"	O
+defense	O
+"	O
+and	O
+"	O
+pain	O
+.	O
+"	O
+To	O
+determine	O
+the	O
+developmental	O
+course	O
+of	O
+defense	O
+and	O
+nociception	O
+,	O
+these	O
+processes	O
+were	O
+analyzed	O
+during	O
+early	O
+ontogeny	O
+in	O
+rats	O
+.	O
+
+Three	O
+large	O
+field	O
+placement	O
+errors	O
+(	O
+two	O
+patients	O
+with	O
+11	O
+.	O
+5	O
+and	O
+16	O
+.	O
+0	O
+mm	O
+distances	O
+of	O
+the	O
+planned	O
+versus	O
+simulated	O
+isocenter	O
+,	O
+respectively	O
+and	O
+one	O
+patient	O
+with	O
+a	O
+7	O
+degree	O
+rotational	O
+error	O
+)	O
+were	O
+detected	O
+and	O
+,	O
+as	O
+with	O
+the	O
+smaller	O
+errors	O
+,	O
+were	O
+immediately	O
+corrected	O
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+catalytically	O
+inactive	O
+version	O
+of	O
+the	O
+Src	B-GENE
+family	I-GENE
+member	O
+,	O
+Lck	B-GENE
+(	O
+lymphoid	B-GENE
+cell	I-GENE
+kinase	I-GENE
+)	O
+,	O
+was	O
+expressed	O
+,	O
+purified	O
+,	O
+and	O
+evaluated	O
+as	O
+a	O
+Csk	B-GENE
+substrate	O
+.	O
+
+A	O
+.	O
+,	O
+Swift	O
+,	O
+A	O
+.	O
+
+Neuronal	O
+mechanisms	O
+underlying	O
+stimulus	O
+-	O
+response	O
+(	O
+S	O
+-	O
+R	O
+)	O
+associations	O
+in	O
+S	O
+-	O
+R	O
+compatibility	O
+tasks	O
+were	O
+identified	O
+in	O
+2	O
+experiments	O
+with	O
+monkeys	O
+.	O
+
+The	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+/	O
+TGF	B-GENE
+-	I-GENE
+alpha	I-GENE
+HCCs	O
+were	O
+also	O
+characterized	O
+by	O
+a	O
+particularly	O
+strong	O
+expression	O
+of	O
+TGF	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	O
+very	O
+low	O
+apoptotic	O
+index	O
+in	O
+contrast	O
+to	O
+high	O
+levels	O
+of	O
+apoptosis	O
+in	O
+peritumorous	O
+tissues	O
+and	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+HCCs	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+the	O
+antagonistic	O
+effects	O
+of	O
+CRP	B-GENE
+and	O
+KdgR	B-GENE
+on	O
+the	O
+expression	O
+of	O
+the	O
+pectinolysis	B-GENE
+genes	I-GENE
+occur	O
+by	O
+different	O
+mechanisms	O
+,	O
+including	O
+direct	O
+competition	O
+between	O
+the	O
+two	O
+regulators	O
+or	O
+between	O
+the	O
+repressor	O
+and	O
+RNA	B-GENE
+polymerase	I-GENE
+for	O
+the	O
+occupation	O
+of	O
+a	O
+common	O
+DNA	O
+region	O
+on	O
+the	O
+target	O
+genes	O
+.	O
+
+The	O
+well	O
+-	O
+known	O
+Rel	B-GENE
+/	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+family	O
+of	O
+vertebrate	O
+transcription	O
+factors	O
+comprises	O
+a	O
+number	O
+of	O
+structurally	O
+related	O
+,	O
+interacting	O
+proteins	O
+that	O
+bind	O
+DNA	O
+as	O
+dimers	O
+and	O
+whose	O
+activity	O
+is	O
+regulated	O
+by	O
+subcellular	O
+location	O
+.	O
+
+The	O
+cglIM	B-GENE
+gene	I-GENE
+is	O
+organized	O
+in	O
+an	O
+unusual	O
+operon	O
+which	O
+contains	O
+,	O
+in	O
+addition	O
+,	O
+two	O
+genes	O
+encoding	O
+stress	O
+-	O
+sensitive	O
+restriction	O
+enzymes	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+investigation	O
+was	O
+to	O
+describe	O
+a	O
+new	O
+formulation	O
+of	O
+silver	O
+sulfadiazine	O
+in	O
+a	O
+water	O
+soluble	O
+gel	O
+,	O
+poloxamer	O
+188	O
+.	O
+
+The	O
+study	O
+goals	O
+were	O
+to	O
+isolate	O
+a	O
+full	O
+-	O
+length	O
+clone	O
+encoding	O
+CO	B-GENE
+-	I-GENE
+Ag	I-GENE
+from	O
+a	O
+bovine	O
+corneal	O
+cDNA	O
+library	O
+and	O
+to	O
+express	O
+this	O
+clone	O
+in	O
+Escherichia	O
+coli	O
+(	O
+E	O
+.	O
+coli	O
+)	O
+.	O
+
+The	O
+gene	O
+contains	O
+six	O
+exons	O
+separated	O
+by	O
+1	O
+.	O
+1	O
+-	O
+5	O
+.	O
+8	O
+kb	O
+introns	O
+and	O
+has	O
+been	O
+localized	O
+to	O
+the	O
+murine	O
+chromosome	O
+2	O
+by	O
+linkage	O
+analysis	O
+.	O
+
+In	O
+Xenopus	O
+embryos	O
+,	O
+the	O
+engineered	B-GENE
+PDGF	I-GENE
+receptor	I-GENE
+protein	I-GENE
+induced	O
+the	O
+formation	O
+of	O
+mesoderm	O
+from	O
+animal	O
+-	O
+pole	O
+explants	O
+in	O
+an	O
+FK1012	O
+-	O
+dependent	O
+manner	O
+.	O
+
+A	O
+cytosolic	O
+variant	O
+of	O
+the	O
+protein	O
+underwent	O
+efficient	O
+transphosphorylation	O
+,	O
+yet	O
+failed	O
+to	O
+activate	O
+appreciably	O
+either	O
+p70	B-GENE
+(	O
+S6k	B-GENE
+)	O
+or	O
+MAP	B-GENE
+kinase	I-GENE
+following	O
+treatment	O
+with	O
+FK1012	O
+.	O
+
+Small	O
+-	O
+molecule	O
+control	O
+of	O
+insulin	B-GENE
+and	O
+PDGF	B-GENE
+receptor	I-GENE
+signaling	O
+and	O
+the	O
+role	O
+of	O
+membrane	O
+attachment	O
+.	O
+
+Conversely	O
+,	O
+the	O
+inactive	O
+dAK	B-GENE
+subunit	I-GENE
+is	O
+progressively	O
+activated	O
+by	O
+1	O
+)	O
+association	O
+with	O
+a	O
+dGK	B-GENE
+or	O
+dCK	B-GENE
+subunit	I-GENE
+and	O
+2	O
+)	O
+the	O
+conformationally	O
+driven	O
+heterotropic	O
+affect	O
+of	O
+dGuo	B-GENE
+or	O
+dCyd	B-GENE
+bound	O
+to	O
+the	O
+opposing	O
+subunit	O
+.	O
+
+CONCLUSIONS	O
+:	O
+A	O
+50	O
+-	O
+mg	O
+daily	O
+dose	O
+of	O
+bicalutamide	O
+is	O
+sufficient	O
+when	O
+given	O
+in	O
+combination	O
+with	O
+an	O
+agent	O
+,	O
+such	O
+as	O
+a	O
+LHRH	B-GENE
+-	O
+A	O
+,	O
+that	O
+lowers	O
+serum	O
+testosterone	O
+,	O
+but	O
+higher	O
+doses	O
+of	O
+bicalutamide	O
+may	O
+be	O
+needed	O
+when	O
+the	O
+drug	O
+is	O
+given	O
+as	O
+monotherapy	O
+.	O
+
+A	O
+genomic	O
+clone	O
+was	O
+isolated	O
+that	O
+contained	O
+12	O
+.	O
+5	O
+kb	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+and	O
+the	O
+first	O
+exon	O
+of	O
+the	O
+p69	B-GENE
+/	I-GENE
+71	I-GENE
+2	I-GENE
+-	I-GENE
+5A	I-GENE
+synthetase	I-GENE
+gene	I-GENE
+.	O
+
+Although	O
+the	O
+gene	O
+is	O
+substantially	O
+smaller	O
+than	O
+the	O
+human	O
+genes	O
+for	O
+other	O
+mitochondrial	O
+enzymes	O
+,	O
+its	O
+intron	O
+/	O
+exon	O
+organization	O
+is	O
+very	O
+similar	O
+,	O
+especially	O
+to	O
+that	O
+of	O
+P450scc	B-GENE
+.	O
+
+RESULTS	O
+:	O
+Looking	O
+at	O
+the	O
+question	O
+of	O
+its	O
+benefits	O
+,	O
+we	O
+were	O
+unable	O
+to	O
+find	O
+any	O
+methodologically	O
+sound	O
+studies	O
+that	O
+have	O
+shown	O
+efficacy	O
+for	O
+EMDR	O
+in	O
+eating	O
+disorders	O
+,	O
+or	O
+,	O
+indeed	O
+,	O
+any	O
+psychiatric	O
+disorder	O
+.	O
+
+Transient	O
+overexpression	O
+of	O
+mutant	B-GENE
+EphB1	I-GENE
+receptors	I-GENE
+(	O
+Y594F	O
+)	O
+blocked	O
+Nck	B-GENE
+recruitment	O
+to	O
+EphB1	B-GENE
+,	O
+attenuated	O
+downstream	O
+JNK	B-GENE
+activation	O
+,	O
+and	O
+blocked	O
+cell	O
+attachment	O
+responses	O
+.	O
+
+S	O
+.	O
+,	O
+and	O
+Walter	O
+,	O
+P	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+Hh	B-GENE
+and	O
+Patched	B-GENE
+(	O
+Ptc	B-GENE
+)	O
+act	O
+through	O
+those	O
+Ci	B-GENE
+binding	O
+sites	O
+to	O
+modulate	O
+the	O
+level	O
+of	O
+Ci	B-GENE
+-	O
+dependent	O
+transcriptional	O
+activation	O
+in	O
+S2	O
+cells	O
+.	O
+
+Furthermore	O
+the	O
+median	O
+increase	O
+in	O
+cyclosporine	O
+DR	O
+/	O
+C	O
+(	O
+SS	O
+trough	O
+)	O
+was	O
+18	O
+l	O
+h	O
+-	O
+1	O
+(	O
+-	O
+3	O
+.	O
+1	O
+to	O
+42	O
+.	O
+1	O
+l	O
+h	O
+-	O
+1	O
+,	O
+interquartile	O
+range	O
+)	O
+.	O
+
+Patients	O
+and	O
+their	O
+relatives	O
+must	O
+be	O
+informed	O
+about	O
+the	O
+available	O
+effective	O
+treatment	O
+possibilities	O
+and	O
+about	O
+the	O
+right	O
+moment	O
+for	O
+their	O
+application	O
+in	O
+an	O
+individual	O
+patient	O
+.	O
+
+Several	O
+PTPases	B-GENE
+were	O
+expressed	O
+abundantly	O
+in	O
+the	O
+5	O
+-	O
+FU	O
+-	O
+treated	O
+bone	O
+marrow	O
+stem	O
+cells	O
+.	O
+
+Expression	O
+of	O
+PTPRO	B-GENE
+was	O
+also	O
+observed	O
+in	O
+human	B-GENE
+CD34	I-GENE
++	I-GENE
+bone	O
+marrow	O
+cells	O
+and	O
+5	O
+-	O
+FU	O
+-	O
+treated	O
+murine	O
+primitive	O
+stem	O
+cells	O
+.	O
+
+The	O
+organization	O
+of	O
+SPP1	B-GENE
+genes	I-GENE
+involved	O
+in	O
+the	O
+replication	O
+,	O
+DNA	O
+packaging	O
+and	O
+phage	O
+assembly	O
+proteins	O
+resembles	O
+the	O
+organization	O
+of	O
+genes	O
+of	O
+equivalent	O
+regions	O
+of	O
+different	O
+E	O
+.	O
+coli	O
+double	O
+-	O
+stranded	O
+DNA	O
+phages	O
+.	O
+
+Our	O
+results	O
+showed	O
+that	O
+compared	O
+to	O
+the	O
+primary	O
+photon	O
+fluence	O
+,	O
+the	O
+extra	O
+-	O
+focal	O
+photon	O
+fluence	O
+from	O
+the	O
+primary	O
+collimator	O
+and	O
+the	O
+flattening	O
+filter	O
+was	O
+11	O
+%	O
+-	O
+16	O
+%	O
+at	O
+the	O
+isocenter	O
+,	O
+among	O
+which	O
+70	O
+%	O
+was	O
+contributed	O
+by	O
+the	O
+flattening	O
+filter	O
+.	O
+
+The	O
+functional	O
+mature	O
+domain	O
+of	O
+pediocin	B-GENE
+AcH	I-GENE
+(	I-GENE
+Lys	I-GENE
++	I-GENE
+1	I-GENE
+to	I-GENE
+Cys	I-GENE
++	I-GENE
+44	I-GENE
+)	I-GENE
+is	O
+targeted	O
+into	O
+the	O
+E	O
+.	O
+coli	O
+sec	O
+machinery	O
+and	O
+secreted	O
+to	O
+the	O
+periplasm	O
+in	O
+active	O
+form	O
+when	O
+fused	O
+in	O
+frame	O
+to	O
+the	O
+COOH	O
+terminus	O
+of	O
+the	O
+secretory	B-GENE
+protein	I-GENE
+maltose	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+MBP	B-GENE
+)	O
+.	O
+
+Isomers	O
+were	O
+differentiated	O
+based	O
+on	O
+the	O
+MS	O
+-	O
+MS	O
+data	O
+of	O
+the	O
+trofluoroacetyl	O
+-	O
+biphenylol	O
+derivatives	O
+.	O
+
+Clinical	O
+value	O
+of	O
+the	O
+estimation	O
+of	O
+growth	O
+kinetics	O
+of	O
+primary	O
+ovarian	O
+cancer	O
+recurrences	O
+by	O
+CA125	B-GENE
+doubling	O
+time	O
+
+This	O
+review	O
+seeks	O
+to	O
+summarize	O
+the	O
+disease	O
+,	O
+to	O
+propose	O
+pathways	O
+of	O
+carcinogenesis	O
+and	O
+to	O
+suggest	O
+ways	O
+in	O
+which	O
+the	O
+"	O
+traditional	O
+"	O
+risk	O
+factors	O
+may	O
+be	O
+interpreted	O
+on	O
+the	O
+basis	O
+of	O
+evolving	O
+knowledge	O
+.	O
+
+The	O
+patient	O
+underwent	O
+two	O
+intracytoplasmic	O
+sperm	O
+injection	O
+cycles	O
+with	O
+thawed	O
+epididymal	O
+spermatozoa	O
+,	O
+in	O
+which	O
+,	O
+due	O
+to	O
+a	O
+pharmacist	O
+'	O
+s	O
+mistake	O
+,	O
+ovarian	O
+stimulation	O
+was	O
+carried	O
+out	O
+by	O
+a	O
+combination	O
+of	O
+long	O
+-	O
+acting	O
+gonadotrophin	B-GENE
+-	I-GENE
+releasing	I-GENE
+hormone	I-GENE
+agonist	O
+(	O
+leuprolide	O
+depot	O
+)	O
+and	O
+gonadotrophins	B-GENE
+.	O
+
+Perhaps	O
+in	O
+addition	O
+to	O
+,	O
+or	O
+as	O
+part	O
+of	O
+,	O
+its	O
+essential	O
+function	O
+in	O
+late	O
+mitosis	O
+,	O
+MOB1	B-GENE
+is	O
+required	O
+for	O
+a	O
+cell	O
+cycle	O
+reset	O
+function	O
+necessary	O
+for	O
+the	O
+initiation	O
+of	O
+the	O
+spindle	O
+pole	O
+body	O
+duplication	O
+.	O
+
+In	O
+contrast	O
+,	O
+overproduction	O
+of	O
+Der3p	B-GENE
+is	O
+lethal	O
+in	O
+a	O
+sec61	B-GENE
+-	I-GENE
+2	I-GENE
+strain	O
+at	O
+the	O
+permissive	O
+temperature	O
+of	O
+25	O
+degrees	O
+C	O
+.	O
+
+Normal	O
+baseline	O
+(	O
+day	O
+-	O
+8	O
+)	O
+PC	O
+levels	O
+(	O
+86	O
+and	O
+89	O
+%	O
+)	O
+were	O
+markedly	O
+reduced	O
+in	O
+both	O
+patients	O
+at	O
+the	O
+time	O
+of	O
+VOD	O
+manifestation	O
+on	O
+day	O
+20	O
+and	O
+40	O
+,	O
+respectively	O
+(	O
+26	O
+and	O
+31	O
+%	O
+)	O
+.	O
+
+To	O
+examine	O
+the	O
+role	O
+of	O
+this	O
+CE2	O
+element	O
+in	O
+regulating	O
+Hoxa1	B-GENE
+expression	O
+in	O
+vivo	O
+,	O
+transgenic	O
+mice	O
+were	O
+generated	O
+which	O
+express	O
+a	O
+Hoxa1	B-GENE
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+reporter	O
+gene	O
+that	O
+contains	O
+a	O
+mutation	O
+in	O
+the	O
+CE2	O
+element	O
+.	O
+
+An	O
+evolutionary	O
+conserved	O
+element	O
+is	O
+essential	O
+for	O
+somite	O
+and	O
+adjacent	O
+mesenchymal	O
+expression	O
+of	O
+the	O
+Hoxa1	B-GENE
+gene	I-GENE
+.	O
+
+RESULTS	O
+:	O
+The	O
+bovine	O
+cDNA	O
+insert	O
+sequence	O
+was	O
+273	O
+nucleotides	O
+in	O
+length	O
+for	O
+the	O
+entire	O
+mRNA	O
+coding	O
+region	O
+,	O
+212	O
+nucleotides	O
+in	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+,	O
+83	O
+nucleotides	O
+in	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+and	O
+a	O
+poly	O
+(	O
+A	O
+)	O
+tail	O
+.	O
+
+Altogether	O
+46	O
+phase	O
+III	O
+activities	O
+were	O
+recorded	O
+.	O
+
+We	O
+have	O
+previously	O
+identified	O
+a	O
+liver	O
+-	O
+enriched	O
+transcription	O
+factor	O
+,	O
+HNF	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+which	O
+is	O
+required	O
+for	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+promoter	I-GENE
+activity	O
+and	O
+also	O
+recognizes	O
+the	O
+regulatory	O
+region	O
+of	O
+numerous	O
+hepatocyte	O
+-	O
+specific	O
+genes	O
+.	O
+
+A	O
+cDNA	O
+clone	O
+was	O
+identified	O
+encoding	O
+a	O
+second	O
+GHS	B-GENE
+-	I-GENE
+R	I-GENE
+-	I-GENE
+related	I-GENE
+gene	I-GENE
+(	O
+GPR39	B-GENE
+)	O
+.	O
+
+(	O
+1997	O
+)	O
+Science	O
+275	O
+,	O
+1927	O
+-	O
+1930	O
+)	O
+.	O
+
+P	O
+.	O
+,	O
+Peyron	O
+,	O
+J	O
+.	O
+
+A	O
+hybridoma	O
+clone	O
+(	O
+7H1	O
+)	O
+resulting	O
+from	O
+the	O
+fusion	O
+between	O
+CEMLAI	O
+/	O
+NP	O
+and	O
+human	O
+embryonic	O
+fibroblasts	O
+MRC5	O
+cells	O
+produced	O
+very	O
+large	O
+amounts	O
+of	O
+P47	B-GENE
+that	O
+was	O
+purified	O
+using	O
+Jacalin	B-GENE
+lectin	I-GENE
+(	O
+specific	O
+for	O
+O	O
+-	O
+glycans	O
+)	O
+and	O
+microsequenced	O
+.	O
+
+This	O
+information	O
+,	O
+together	O
+with	O
+estimation	O
+of	O
+the	O
+size	O
+of	O
+the	O
+deglycosylated	O
+A	O
+subunit	O
+relative	O
+to	O
+a	O
+series	O
+of	O
+C	B-GENE
+-	I-GENE
+terminal	I-GENE
+truncated	I-GENE
+TSHR	I-GENE
+ectodomain	I-GENE
+variants	I-GENE
+,	O
+places	O
+cleavage	O
+Site	O
+1	O
+in	O
+the	O
+vicinity	O
+of	O
+,	O
+or	O
+closely	O
+upstream	O
+to	O
+,	O
+residue	O
+317	O
+.	O
+
+In	O
+vitro	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+of	O
+the	O
+200	O
+-	O
+bp	O
+proximal	O
+region	O
+of	O
+the	O
+promoter	O
+with	O
+a	O
+murine	O
+Hepa	O
+1	O
+-	O
+6	O
+cell	O
+nuclear	O
+extract	O
+revealed	O
+a	O
+clear	O
+footprint	O
+of	O
+a	O
+region	O
+corresponding	O
+to	O
+-	O
+80	O
+to	O
+-	O
+28	O
+bp	O
+of	O
+the	O
+murine	B-GENE
+fVII	I-GENE
+gene	I-GENE
+,	O
+suggesting	O
+that	O
+liver	O
+factors	O
+interact	O
+with	O
+this	O
+region	O
+of	O
+the	O
+DNA	O
+.	O
+
+Both	O
+increasing	O
+basal	O
+FSH	B-GENE
+and	O
+age	O
+were	O
+associated	O
+significantly	O
+with	O
+increased	O
+total	O
+gonadotrophin	B-GENE
+dose	O
+,	O
+and	O
+reduced	O
+number	O
+of	O
+oocytes	O
+collected	O
+and	O
+pregnancy	O
+rate	O
+.	O
+
+A	O
+comparative	O
+study	O
+was	O
+undertaken	O
+between	O
+an	O
+enzymatic	O
+immunohistochemical	O
+technique	O
+(	O
+EIT	O
+)	O
+developed	O
+for	O
+the	O
+diagnosis	O
+of	O
+human	O
+trichinellosis	O
+and	O
+the	O
+indirect	O
+immunofluorescence	O
+test	O
+(	O
+IIF	O
+)	O
+,	O
+analysing	O
+sera	O
+from	O
+outbreaks	O
+of	O
+human	O
+trichinellosis	O
+in	O
+Argentina	O
+.	O
+
+Our	O
+results	O
+establish	O
+GKLF	B-GENE
+as	O
+a	O
+sequence	O
+-	O
+specific	O
+transcription	O
+factor	O
+likely	O
+involved	O
+in	O
+regulation	O
+of	O
+expression	O
+of	O
+endogenous	O
+genes	O
+.	O
+
+CES4	B-GENE
+on	O
+a	O
+multicopy	O
+plasmid	O
+was	O
+unable	O
+to	O
+suppress	O
+tif1	B-GENE
+-	I-GENE
+A79V	I-GENE
+.	O
+
+Here	O
+we	O
+report	O
+that	O
+in	O
+cultured	O
+cells	O
+from	O
+Drosophila	O
+melanogaster	O
+human	B-GENE
+Sp1	I-GENE
+efficiently	O
+activates	O
+transcription	O
+from	O
+synthetic	O
+promoters	O
+containing	O
+TATA	O
+boxes	O
+,	O
+but	O
+not	O
+from	O
+promoters	O
+that	O
+contain	O
+an	O
+initiator	O
+instead	O
+of	O
+a	O
+TATA	O
+box	O
+.	O
+
+No	O
+apparent	O
+clinical	O
+signs	O
+indicative	O
+of	O
+systemic	O
+toxicity	O
+were	O
+observed	O
+in	O
+the	O
+F0	O
+and	O
+F1	O
+animals	O
+of	O
+either	O
+sex	O
+.	O
+
+In	O
+an	O
+effort	O
+to	O
+identify	O
+the	O
+USH1C	B-GENE
+disease	I-GENE
+gene	I-GENE
+we	O
+have	O
+isolated	O
+the	O
+region	O
+between	O
+these	O
+markers	O
+in	O
+yeast	O
+artificial	O
+chromosomes	O
+(	O
+YACs	O
+)	O
+using	O
+a	O
+combination	O
+of	O
+STS	O
+content	O
+mapping	O
+and	O
+Alu	B-GENE
+-	O
+PCR	O
+hybridization	O
+.	O
+
+PowerBLAST	O
+analysis	O
+identified	O
+six	O
+clusters	O
+of	O
+expressed	O
+sequence	O
+tags	O
+(	O
+ESTs	O
+)	O
+,	O
+two	O
+known	O
+genes	O
+(	O
+BIR	B-GENE
+,	O
+SUR1	B-GENE
+)	O
+mapped	O
+previously	O
+to	O
+this	O
+region	O
+,	O
+and	O
+a	O
+previously	O
+characterized	O
+but	O
+unmapped	O
+gene	B-GENE
+NEFA	I-GENE
+(	O
+DNA	B-GENE
+binding	I-GENE
+/	I-GENE
+EF	I-GENE
+hand	I-GENE
+/	I-GENE
+acidic	I-GENE
+amino	I-GENE
+-	I-GENE
+acid	I-GENE
+-	I-GENE
+rich	I-GENE
+)	O
+.	O
+
+A	O
+fusion	O
+protein	O
+composed	O
+of	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+and	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+Ahr	I-GENE
+translocates	O
+from	O
+the	O
+cytoplasm	O
+to	O
+the	O
+nucleus	O
+in	O
+a	O
+ligand	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Reconstitution	O
+of	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+was	O
+observed	O
+only	O
+with	O
+kinase	O
+active	O
+Jak1	B-GENE
+in	O
+both	O
+cell	O
+lines	O
+.	O
+
+In	O
+addition	O
+,	O
+negatively	O
+regulatory	O
+region	O
+may	O
+exist	O
+from	O
+-	O
+1782	O
+to	O
+-	O
+1295	O
+bp	O
+.	O
+
+The	O
+hypothesis	O
+of	O
+Geisler	O
+(	O
+Brain	O
+Res	O
+.	O
+
+The	O
+second	O
+transcript	O
+,	O
+rhis4l	B-GENE
+,	O
+is	O
+bicistronic	O
+.	O
+
+Consistent	O
+with	O
+this	O
+interpretation	O
+,	O
+a	O
+mutant	O
+form	O
+of	O
+XRN1	B-GENE
+,	O
+which	O
+encodes	O
+a	O
+5	O
+'	O
+-	O
+3	O
+'	O
+exonuclease	O
+,	O
+was	O
+identified	O
+as	O
+an	O
+extragenic	O
+suppressor	O
+that	O
+increases	O
+the	O
+half	O
+-	O
+life	O
+of	O
+rhis4	B-GENE
+mRNA	I-GENE
+,	O
+leading	O
+to	O
+a	O
+10	O
+-	O
+fold	O
+increase	O
+in	O
+steady	O
+-	O
+state	O
+mRNA	O
+levels	O
+compared	O
+to	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+HIS4	I-GENE
+mRNA	I-GENE
+level	O
+.	O
+
+Sip1	B-GENE
+was	O
+initially	O
+identified	O
+by	O
+virtue	O
+of	O
+its	O
+interaction	O
+with	O
+SC35	B-GENE
+,	O
+a	O
+splicing	O
+factor	O
+of	O
+the	O
+SR	B-GENE
+family	I-GENE
+.	O
+
+Such	O
+mutations	O
+are	O
+thought	O
+to	O
+exert	O
+their	O
+dominant	O
+phenotype	O
+by	O
+sequestration	O
+of	O
+the	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factor	I-GENE
+(	O
+GNEF	B-GENE
+)	O
+.	O
+
+Several	O
+studies	O
+have	O
+characterized	O
+the	O
+upstream	O
+regulatory	O
+region	O
+of	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+,	O
+and	O
+identified	O
+cis	O
+-	O
+acting	O
+elements	O
+termed	O
+the	O
+cyclic	O
+AMP	O
+(	O
+cAMP	O
+)	O
+response	O
+elements	O
+(	O
+CREs	O
+)	O
+that	O
+are	O
+critical	O
+for	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+transcription	O
+in	O
+response	O
+to	O
+a	O
+variety	O
+of	O
+extracellular	O
+stimuli	O
+.	O
+
+We	O
+have	O
+cloned	O
+a	O
+kinase	O
+,	O
+Nlk	B-GENE
+,	O
+that	O
+is	O
+a	O
+murine	B-GENE
+homolog	I-GENE
+of	I-GENE
+the	I-GENE
+Drosophila	I-GENE
+nemo	I-GENE
+(	O
+nmo	B-GENE
+)	O
+gene	O
+.	O
+
+Our	O
+findings	O
+suggest	O
+that	O
+striatal	O
+FDG	O
+and	O
+particularly	O
+RACLO	O
+are	O
+sensitive	O
+and	O
+effective	O
+measures	O
+of	O
+striatal	O
+function	O
+and	O
+may	O
+help	O
+characterizing	O
+patients	O
+with	O
+multiple	O
+system	O
+atrophy	O
+.	O
+
+Childhood	O
+misbehavior	O
+and	O
+the	O
+risk	O
+of	O
+injecting	O
+drug	O
+use	O
+.	O
+
+Genetic	O
+analysis	O
+has	O
+subsequently	O
+identified	O
+subpathways	O
+of	O
+the	O
+DNA	O
+structure	O
+checkpoints	O
+,	O
+including	O
+the	O
+reversible	O
+arrest	O
+of	O
+DNA	O
+synthesis	O
+.	O
+
+Thus	O
+,	O
+Esigma54	B-GENE
+promoters	I-GENE
+are	O
+responsive	O
+to	O
+CRP	B-GENE
+,	O
+a	O
+protein	O
+unrelated	O
+to	O
+sigma54	B-GENE
+activators	I-GENE
+,	O
+and	O
+the	O
+repression	O
+exerted	O
+is	O
+the	O
+direct	O
+result	O
+of	O
+an	O
+interaction	O
+between	O
+Esigma54	B-GENE
+and	O
+the	O
+CRP	B-GENE
+-	I-GENE
+cAMP	I-GENE
+complex	I-GENE
+.	O
+
+GlcNAc	O
+-	O
+and	O
+GlcNAc2	O
+-	O
+PP	O
+-	O
+Dolichol	O
+biosynthesis	O
+could	O
+be	O
+shown	O
+with	O
+isolated	O
+S	O
+.	O
+cerevisiae	O
+membranes	O
+from	O
+cells	O
+harboring	O
+the	O
+recombinant	O
+plasmid	O
+and	O
+grown	O
+on	O
+glucose	O
+thus	O
+suppressing	O
+transcription	O
+of	O
+the	O
+endogenous	O
+gene	O
+.	O
+
+Antibodies	O
+raised	O
+against	O
+GST	B-GENE
+mSH2	I-GENE
+-	I-GENE
+B	I-GENE
+identified	O
+a	O
+cellular	O
+protein	O
+of	O
+92	O
+kDa	O
+that	O
+was	O
+not	O
+found	O
+to	O
+be	O
+phosphorylated	O
+on	O
+Tyr	O
+.	O
+
+Interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+)	O
+is	O
+a	O
+pleiotropic	O
+cytokine	O
+,	O
+which	O
+is	O
+involved	O
+in	O
+inflammatory	O
+and	O
+immune	O
+responses	O
+,	O
+acute	O
+phase	O
+reactions	O
+,	O
+and	O
+hematopoiesis	O
+.	O
+
+Upon	O
+analysis	O
+of	O
+various	O
+deletion	O
+and	O
+point	O
+-	O
+mutated	O
+variants	O
+of	O
+the	O
+human	B-GENE
+IL	I-GENE
+-	I-GENE
+6	I-GENE
+gene	I-GENE
+promoter	I-GENE
+coupled	O
+to	O
+a	O
+reporter	O
+gene	O
+,	O
+we	O
+screened	O
+for	O
+possible	O
+cooperating	O
+transcription	O
+factors	O
+.	O
+
+This	O
+region	O
+,	O
+however	O
+,	O
+contains	O
+a	O
+CCAATC	O
+box	O
+in	O
+the	O
+reverse	O
+complement	O
+and	O
+several	O
+GC	O
+boxes	O
+that	O
+are	O
+recognition	O
+sites	O
+for	O
+SP1	B-GENE
+.	O
+
+Our	O
+purpose	O
+was	O
+to	O
+determine	O
+if	O
+intact	O
+perianal	O
+(	O
+S4	O
+-	O
+5	O
+)	O
+pin	O
+sensation	O
+(	O
+PPS	O
+)	O
+and	O
+bulbocavernosus	O
+(	O
+S2	O
+-	O
+4	O
+)	O
+reflex	O
+(	O
+BCR	O
+)	O
+shortly	O
+after	O
+spinal	O
+cord	O
+injury	O
+(	O
+SCI	O
+)	O
+are	O
+predictive	O
+of	O
+bladder	O
+function	O
+recovery	O
+.	O
+
+The	O
+correct	O
+termination	O
+of	O
+retroviral	O
+transcripts	O
+at	O
+the	O
+3	O
+'	O
+LTR	O
+R	O
+/	O
+U5	O
+junction	O
+is	O
+primarily	O
+dependent	O
+on	O
+the	O
+canonical	O
+AAUAAA	O
+polyadenylation	O
+signal	O
+,	O
+so	O
+we	O
+have	O
+analyzed	O
+the	O
+effect	O
+of	O
+mutating	O
+the	O
+polyadenylation	O
+signal	O
+sequences	O
+on	O
+the	O
+properties	O
+of	O
+a	O
+selectable	O
+murine	O
+retroviral	O
+vector	O
+.	O
+
+ALT	B-GENE
+levels	O
+in	O
+responders	O
+were	O
+lowered	O
+by	O
+46	O
+%	O
+and	O
+AST	B-GENE
+levels	O
+were	O
+lowered	O
+by	O
+35	O
+%	O
+after	O
+12	O
+weeks	O
+of	O
+vitamin	O
+E	O
+treatment	O
+.	O
+
+51	O
+.	O
+9	O
+%	O
+(	O
+P	O
+=	O
+0	O
+.	O
+0006	O
+)	O
+in	O
+the	O
+MMF	O
+versus	O
+the	O
+AZA	O
+groups	O
+,	O
+respectively	O
+.	O
+
+Our	O
+study	O
+was	O
+designed	O
+to	O
+investigate	O
+the	O
+effect	O
+of	O
+MMF	O
+on	O
+in	O
+vivo	O
+bone	O
+mineral	O
+metabolism	O
+.	O
+
+Pao2	O
+increased	O
+from	O
+15	O
+.	O
+5	O
++	O
+/	O
+-	O
+5	O
+.	O
+6	O
+kPa	O
+(	O
+116	O
++	O
+/	O
+-	O
+42	O
+mm	O
+Hg	O
+)	O
+to	O
+17	O
+.	O
+3	O
++	O
+/	O
+-	O
+6	O
+.	O
+3	O
+kPa	O
+(	O
+130	O
++	O
+/	O
+-	O
+47	O
+mm	O
+Hg	O
+)	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Typical	O
+configurations	O
+of	O
+psychosocial	O
+stress	O
+factors	O
+of	O
+psychiatrically	O
+conspicuous	O
+children	O
+and	O
+adolescents	O
+
+Nine	O
+cats	O
+received	O
+PMEA	O
+at	O
+a	O
+dosage	O
+of	O
+10	O
+mg	O
+/	O
+kg	O
+body	O
+weight	O
+,	O
+nine	O
+cats	O
+received	O
+FPMPA	O
+at	O
+a	O
+dosage	O
+of	O
+25	O
+mg	O
+/	O
+kg	O
+body	O
+weight	O
+.	O
+
+Resistance	O
+to	O
+thyroid	O
+hormone	O
+:	O
+implications	O
+for	O
+neurodevelopmental	O
+research	O
+on	O
+the	O
+effects	O
+of	O
+thyroid	O
+hormone	O
+disruptors	O
+.	O
+
+We	O
+present	O
+the	O
+preliminary	O
+results	O
+obtained	O
+on	O
+36	O
+patients	O
+which	O
+were	O
+followed	O
+for	O
+a	O
+mean	O
+period	O
+of	O
+12	O
+months	O
+.	O
+
+Moreover	O
+,	O
+xTAK1KN	B-GENE
+could	O
+block	O
+the	O
+expression	O
+of	O
+ventral	O
+mesoderm	O
+marker	O
+genes	O
+induced	O
+by	O
+Smad1	B-GENE
+or	I-GENE
+5	I-GENE
+.	O
+
+The	O
+assay	O
+exhibits	O
+a	O
+dynamic	O
+range	O
+of	O
+0	O
+.	O
+1	O
+-	O
+100	O
+micrograms	O
+l	O
+-	O
+1	O
+using	O
+a	O
+monoclonal	O
+antibody	O
+or	O
+alternatively	O
+10	O
+micrograms	O
+l	O
+-	O
+1	O
+to	O
+10	O
+mg	O
+l	O
+-	O
+1	O
+using	O
+commercially	O
+available	O
+antiserum	O
+.	O
+
+A	O
+canonical	O
+TATA	O
+box	O
+was	O
+not	O
+detected	O
+.	O
+
+Expression	O
+and	O
+characterization	O
+of	O
+recombinant	B-GENE
+single	I-GENE
+-	I-GENE
+chain	I-GENE
+Fv	I-GENE
+and	O
+Fv	B-GENE
+fragments	I-GENE
+derived	O
+from	O
+a	O
+set	O
+of	O
+catalytic	O
+antibodies	O
+.	O
+
+A	O
+putative	O
+inhibitor	O
+(	O
+s	O
+)	O
+appears	O
+to	O
+co	O
+-	O
+elute	O
+in	O
+the	O
+inactive	O
+fraction	O
+that	O
+blocked	O
+the	O
+L	B-GENE
+(	I-GENE
+alpha	I-GENE
+)	I-GENE
+activity	O
+.	O
+
+Platelet	O
+aggregation	O
+in	O
+response	O
+to	O
+10	O
+micrograms	O
+collagen	B-GENE
+/	O
+ml	O
+was	O
+decreased	O
+in	O
+parallel	O
+after	O
+treatment	O
+with	O
+ASA	O
+.	O
+
+Using	O
+himA	B-GENE
+mutants	I-GENE
+,	O
+we	O
+confirmed	O
+that	O
+IHF	B-GENE
+plays	O
+a	O
+role	O
+in	O
+the	O
+molybdate	O
+-	O
+dependent	O
+regulation	O
+of	O
+dmsA	B-GENE
+-	O
+lacZ	B-GENE
+expression	O
+in	O
+vivo	O
+.	O
+
+Cross	O
+-	O
+talking	O
+among	O
+Drosophila	O
+nuclear	O
+receptors	O
+at	O
+the	O
+promiscuous	O
+response	O
+element	O
+of	O
+the	O
+ng	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+ng	B-GENE
+-	I-GENE
+2	I-GENE
+intermolt	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+ipsilateral	O
+breast	O
+tumor	O
+relapse	O
+rate	O
+was	O
+similar	O
+between	O
+the	O
+PALP	O
+and	O
+MGDET	O
+groups	O
+.	O
+
+Sibling	O
+aggregation	O
+of	O
+low	B-GENE
+-	I-GENE
+and	I-GENE
+high	I-GENE
+-	I-GENE
+density	I-GENE
+lipoprotein	I-GENE
+cholesterol	I-GENE
+and	O
+apolipoproteins	B-GENE
+B	I-GENE
+and	I-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+levels	O
+in	O
+black	O
+and	O
+white	O
+children	O
+:	O
+the	O
+Bogalusa	O
+Heart	O
+Study	O
+.	O
+
+The	O
+CAPLC1	B-GENE
+protein	I-GENE
+also	O
+exhibited	O
+several	O
+unique	O
+features	O
+,	O
+including	O
+a	O
+novel	O
+stretch	O
+of	O
+18	O
+-	O
+19	O
+amino	O
+acid	O
+residues	O
+within	O
+the	O
+X	O
+domain	O
+and	O
+an	O
+unusually	O
+long	O
+N	O
+-	O
+terminus	O
+which	O
+did	O
+not	O
+contain	O
+a	O
+recognizable	O
+EF	O
+-	O
+hand	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+-	O
+binding	O
+domain	O
+.	O
+
+This	O
+hypothesis	O
+is	O
+consistent	O
+with	O
+the	O
+occurrence	O
+of	O
+PEA3	B-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+the	O
+PEA3	B-GENE
+promoter	I-GENE
+and	O
+with	O
+the	O
+ability	O
+of	O
+PEA3	B-GENE
+to	O
+transactivate	O
+this	O
+promoter	O
+.	O
+
+Pet	B-GENE
+-	I-GENE
+1	I-GENE
+can	O
+bind	O
+specifically	O
+to	O
+a	O
+PEA3	B-GENE
+ETS	B-GENE
+DNA	O
+-	O
+binding	O
+motif	O
+and	O
+can	O
+modulate	O
+transcription	O
+of	O
+synthetic	O
+promoter	O
+constructs	O
+in	O
+a	O
+sequence	O
+-	O
+specific	O
+manner	O
+.	O
+
+The	O
+protein	O
+expressed	O
+by	O
+F2771	B-GENE
+cDNA	I-GENE
+in	O
+transfected	O
+COS	O
+cells	O
+is	O
+localized	O
+in	O
+the	O
+cytoplasm	O
+.	O
+
+Northern	O
+analysis	O
+indicated	O
+differential	O
+expression	O
+by	O
+tissue	O
+with	O
+highest	O
+expression	O
+in	O
+the	O
+heart	O
+.	O
+
+As	O
+well	O
+,	O
+further	O
+deletion	O
+of	O
+the	O
+promoter	O
+region	O
+to	O
+nucleotide	O
+-	O
+110	O
+,	O
+which	O
+contains	O
+only	O
+one	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+site	I-GENE
+,	O
+still	O
+retained	O
+the	O
+ability	O
+to	O
+respond	O
+to	O
+exogenous	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+The	O
+observation	O
+that	O
+beta	B-GENE
+2m	I-GENE
+with	O
+covalently	O
+attached	O
+peptide	O
+can	O
+effectively	O
+create	O
+CTL	O
+target	O
+structures	O
+in	O
+vitro	O
+offers	O
+new	O
+possibilities	O
+for	O
+the	O
+in	O
+vivo	O
+induction	O
+of	O
+epitope	O
+-	O
+specific	O
+CTL	O
+responses	O
+by	O
+either	O
+DNA	O
+immunization	O
+or	O
+injection	O
+of	O
+the	O
+purified	O
+epitope	O
+-	O
+linked	O
+beta	B-GENE
+2m	I-GENE
+.	O
+
+The	O
+mRNAs	O
+of	O
+these	O
+genes	O
+contain	O
+respectively	O
+one	O
+(	O
+YAP1	B-GENE
+uORF	I-GENE
+)	O
+and	O
+two	O
+(	O
+YAP2	B-GENE
+uORF1	I-GENE
+and	O
+uORF2	O
+)	O
+upstream	O
+open	O
+reading	O
+frames	O
+.	O
+uORF	O
+-	O
+mediated	O
+modulation	O
+of	O
+post	O
+-	O
+termination	O
+events	O
+on	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+(	O
+5	O
+'	O
+-	O
+UTR	O
+)	O
+directs	O
+differential	O
+control	O
+not	O
+only	O
+of	O
+translation	O
+but	O
+also	O
+of	O
+mRNA	O
+decay	O
+.	O
+
+To	O
+further	O
+investigate	O
+the	O
+nature	O
+of	O
+the	O
+site	O
+specificity	O
+a	O
+set	O
+of	O
+deletion	O
+mutants	O
+of	O
+the	O
+160	O
+bp	O
+sequence	O
+were	O
+analysed	O
+.	O
+
+In	O
+the	O
+tissues	O
+tested	O
+,	O
+except	O
+brain	O
+,	O
+the	O
+message	O
+for	O
+CLIP	B-GENE
+-	I-GENE
+170	I-GENE
+was	O
+more	O
+abundant	O
+than	O
+that	O
+for	O
+Restin	B-GENE
+.	O
+
+BACKGROUND	O
+:	O
+Chemicals	O
+vary	O
+considerably	O
+in	O
+their	O
+intrinsic	O
+ability	O
+to	O
+cause	O
+allergic	O
+contact	O
+dermatitis	O
+.	O
+
+Also	O
+,	O
+the	O
+deduced	O
+amino	O
+acids	O
+of	O
+the	O
+antigenic	B-GENE
+regions	I-GENE
+A	I-GENE
+,	I-GENE
+B	I-GENE
+and	I-GENE
+C	I-GENE
+of	I-GENE
+VP7	I-GENE
+were	O
+nearly	O
+conserved	O
+within	O
+the	O
+phylogenetic	O
+lineages	O
+.	O
+
+The	O
+cloned	O
+alcR	B-GENE
+gene	I-GENE
+provided	O
+in	O
+trans	O
+restored	O
+these	O
+siderophore	O
+system	O
+activities	O
+to	O
+the	O
+mutants	O
+.	O
+
+The	O
+cloned	O
+alcR	B-GENE
+gene	I-GENE
+provided	O
+in	O
+trans	O
+restored	O
+these	O
+siderophore	O
+system	O
+activities	O
+to	O
+the	O
+mutants	O
+.	O
+
+Copyright	O
+1998	O
+Academic	O
+Press	O
+.	O
+
+It	O
+may	O
+also	O
+be	O
+suggested	O
+that	O
+particular	O
+care	O
+should	O
+be	O
+taken	O
+when	O
+such	O
+a	O
+trans	O
+-	O
+dominant	O
+Rev	B-GENE
+mutant	I-GENE
+is	O
+considered	O
+to	O
+be	O
+used	O
+as	O
+a	O
+genetic	O
+therapy	O
+against	O
+HIV	O
+-	O
+I	O
+infection	O
+,	O
+in	O
+individuals	O
+infected	O
+with	O
+both	O
+HIV	O
+-	O
+I	O
+and	O
+HTLV	O
+-	O
+1	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Between	O
+January	O
+1992	O
+and	O
+June	O
+1994	O
+at	O
+St	O
+.	O
+
+The	O
+frequency	O
+of	O
+SPs	O
+for	O
+both	O
+the	O
+moderate	O
+and	O
+severe	O
+groups	O
+was	O
+significantly	O
+higher	O
+than	O
+that	O
+in	O
+patients	O
+with	O
+a	O
+normal	O
+MMFCV	O
+(	O
+p	O
+<	O
+.	O
+01	O
+)	O
+;	O
+of	O
+154	O
+arms	O
+with	O
+a	O
+normal	O
+MMFCV	O
+,	O
+only	O
+9	O
+(	O
+6	O
+%	O
+)	O
+had	O
+an	O
+SP	O
+.	O
+
+We	O
+analyzed	O
+the	O
+P	O
+-	O
+SAECG	O
+in	O
+the	O
+time	O
+and	O
+frequency	O
+domain	O
+in	O
+23	O
+patients	O
+with	O
+Paf	O
+and	O
+19	O
+controls	O
+.	O
+
+Competitive	O
+reverse	O
+transcription	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+and	O
+HPLC	O
+analysis	O
+showed	O
+that	O
+RUSH	B-GENE
+-	I-GENE
+1alpha	I-GENE
+is	O
+the	O
+progesterone	O
+-	O
+dependent	O
+splice	O
+variant	O
+.	O
+
+TOR2	B-GENE
+is	O
+part	O
+of	O
+two	O
+related	O
+signaling	O
+pathways	O
+coordinating	O
+cell	O
+growth	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Transcervical	O
+amnioinfusion	O
+.	O
+
+SETTING	O
+:	O
+A	O
+division	O
+of	O
+a	O
+large	O
+tea	O
+plantation	O
+in	O
+Kandy	O
+.	O
+
+Simple	O
+models	O
+of	O
+bimolecular	O
+interaction	O
+did	O
+not	O
+fully	O
+account	O
+for	O
+the	O
+kinetic	O
+profiles	O
+obtained	O
+with	O
+the	O
+parental	O
+antibodies	O
+and	O
+the	O
+hybrids	O
+,	O
+and	O
+this	O
+complexity	O
+suggested	O
+the	O
+existence	O
+of	O
+a	O
+conformational	O
+heterogeneity	O
+in	O
+these	O
+molecules	O
+.	O
+
+In	O
+order	O
+to	O
+decipher	O
+the	O
+pathway	O
+that	O
+leads	O
+to	O
+Hox	B-GENE
+gene	I-GENE
+induction	O
+,	O
+we	O
+have	O
+investigated	O
+whether	O
+a	O
+Hox	B-GENE
+gene	I-GENE
+regulator	O
+,	O
+the	O
+leucine	O
+zipper	O
+transcription	O
+factor	O
+MafB	B-GENE
+/	O
+Kr	B-GENE
+,	O
+is	O
+itself	O
+transcriptionally	O
+regulated	O
+by	O
+the	O
+environmental	O
+signals	O
+.	O
+
+Reporter	O
+constructs	O
+function	O
+in	O
+a	O
+parallel	O
+manner	O
+,	O
+demonstrating	O
+the	O
+key	O
+role	O
+of	O
+the	O
+AhR	B-GENE
+in	O
+constitutive	O
+as	O
+well	O
+as	O
+TCDD	O
+-	O
+induced	O
+expression	O
+of	O
+Cyp1B1	B-GENE
+in	O
+mouse	O
+embryo	O
+fibroblasts	O
+.	O
+
+Transfection	O
+studies	O
+also	O
+showed	O
+that	O
+3	O
+'	O
+-	O
+deletion	O
+of	O
+sequences	O
+downstream	O
+of	O
+the	O
+transcriptional	O
+start	O
+site	O
+(	O
++	O
+1	O
+/	O
++	O
+47	O
+)	O
+markedly	O
+reduced	O
+OSM	B-GENE
+-	O
+fold	O
+induction	O
+.	O
+
+Oncostatin	B-GENE
+M	I-GENE
+stimulates	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+to	O
+bind	O
+a	O
+transcriptionally	O
+responsive	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+element	I-GENE
+within	O
+the	O
+tissue	B-GENE
+inhibitor	I-GENE
+of	I-GENE
+metalloproteinase	I-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+new	O
+human	B-GENE
+RING	I-GENE
+-	I-GENE
+finger	I-GENE
+gene	I-GENE
+(	O
+RNF4	B-GENE
+)	O
+that	O
+encodes	O
+a	O
+190	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+.	O
+
+To	O
+elucidate	O
+the	O
+regulatory	O
+mechanism	O
+of	O
+human	B-GENE
+AM	I-GENE
+gene	I-GENE
+expression	O
+,	O
+functional	O
+elements	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+AM	B-GENE
+gene	I-GENE
+were	O
+studied	O
+in	O
+human	O
+aortic	O
+endothelial	O
+cells	O
+(	O
+HAEC	O
+)	O
+.	O
+
+Soluble	O
+FasR	B-GENE
+ligand	O
+-	O
+binding	O
+domain	O
+:	O
+high	O
+-	O
+yield	O
+production	O
+of	O
+active	O
+fusion	O
+and	O
+non	O
+-	O
+fusion	O
+recombinant	O
+proteins	O
+using	O
+the	O
+baculovirus	O
+/	O
+insect	O
+cell	O
+system	O
+.	O
+
+The	O
+inhibition	O
+of	O
+focus	O
+formation	O
+observed	O
+in	O
+the	O
+presence	O
+of	O
+C3G	B-GENE
+was	O
+not	O
+due	O
+to	O
+toxic	O
+effects	O
+on	O
+cell	O
+viability	O
+,	O
+since	O
+transfected	O
+C3G	B-GENE
+cells	O
+exhibited	O
+the	O
+same	O
+survival	O
+and	O
+growth	O
+rates	O
+as	O
+untransfected	O
+NIH3T3	O
+cells	O
+or	O
+cells	O
+transfected	O
+with	O
+plasmid	O
+vector	O
+alone	O
+.	O
+
+C	O
+.	O
+D2	O
+-	O
+Chr	O
+4	O
+congenic	O
+strains	O
+harboring	O
+DBA	O
+/	O
+2	O
+alleles	O
+associated	O
+with	O
+the	O
+Pctr1	B-GENE
+locus	I-GENE
+contained	O
+DBA	O
+/	O
+2	O
+"	O
+resistant	O
+"	O
+alleles	O
+of	O
+the	O
+CDK4	B-GENE
+/	O
+CDK6	B-GENE
+inhibitors	O
+p16	B-GENE
+and	O
+p15	B-GENE
+.	O
+
+When	O
+tested	O
+with	O
+wild	O
+-	O
+type	O
+(	O
+DBA	O
+/	O
+2	O
+)	O
+p16	B-GENE
+,	O
+both	O
+A134C	O
+and	O
+G232A	O
+BALB	O
+/	O
+c	O
+-	O
+specific	O
+variants	O
+of	O
+p16	B-GENE
+were	O
+inefficient	O
+in	O
+their	O
+ability	O
+to	O
+inhibit	O
+the	O
+activity	O
+of	O
+cyclin	B-GENE
+D2	I-GENE
+/	O
+CDK4	B-GENE
+in	O
+kinase	O
+assays	O
+with	O
+retinoblastoma	B-GENE
+protein	I-GENE
+,	O
+suggesting	O
+this	O
+defective	O
+,	O
+inherited	O
+allele	O
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+genetic	O
+susceptibility	O
+of	O
+BALB	O
+/	O
+c	O
+mice	O
+for	O
+plasmacytoma	O
+induction	O
+and	O
+that	O
+p16	B-GENE
+(	O
+INK4a	B-GENE
+)	O
+is	O
+a	O
+strong	O
+candidate	O
+for	O
+the	O
+Pctr1	B-GENE
+locus	I-GENE
+.	O
+
+Despite	O
+this	O
+there	O
+was	O
+no	O
+difference	O
+in	O
+the	O
+intubating	O
+conditions	O
+at	O
+one	O
+minute	O
+with	O
+25	O
+excellent	O
+/	O
+5	O
+good	O
+in	O
+the	O
+suxamethonium	O
+group	O
+and	O
+27	O
+excellent	O
+/	O
+3	O
+good	O
+in	O
+the	O
+rocuronium	O
+group	O
+.	O
+
+Cloning	O
+and	O
+expression	O
+of	O
+two	O
+genes	O
+encoding	O
+auxin	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+from	O
+tobacco	O
+.	O
+
+Furthermore	O
+,	O
+direct	O
+association	O
+with	O
+D3	O
+phosphatidylinositides	O
+seems	O
+to	O
+be	O
+essential	O
+for	O
+activation	O
+of	O
+PKB	B-GENE
+/	O
+Akt	B-GENE
+.	O
+
+The	O
+FMN	O
+moiety	O
+but	O
+not	O
+the	O
+[	O
+3Fe	O
+-	O
+4S	O
+]	O
+cluster	O
+of	O
+the	O
+subunit	O
+appears	O
+to	O
+participate	O
+in	O
+this	O
+reaction	O
+.	O
+
+Alison	O
+Bell	O
+Memorial	O
+Award	O
+.	O
+
+METHODS	O
+:	O
+A	O
+population	O
+survey	O
+was	O
+undertaken	O
+in	O
+10	O
+,	O
+148	O
+individuals	O
+to	O
+measure	O
+the	O
+prevalence	O
+and	O
+identify	O
+the	O
+causes	O
+of	O
+blindness	O
+in	O
+Lebanon	O
+.	O
+
+The	O
+mean	O
+duration	O
+of	O
+pain	O
+relief	O
+was	O
+4	O
+-	O
+6	O
+weeks	O
+.	O
+
+The	O
+ESEM	O
+differs	O
+from	O
+conventional	O
+SEM	O
+in	O
+that	O
+no	O
+sample	O
+preparation	O
+is	O
+needed	O
+,	O
+eliminating	O
+artifactual	O
+changes	O
+.	O
+
+The	O
+3	O
+'	O
+fragment	O
+was	O
+shown	O
+to	O
+accumulate	O
+as	O
+full	O
+-	O
+length	O
+mRNA	O
+disappeared	O
+in	O
+actinomycin	O
+D	O
+-	O
+treated	O
+cells	O
+,	O
+indicating	O
+a	O
+precursor	O
+-	O
+product	O
+relationship	O
+.	O
+
+The	O
+TATA	B-GENE
+box	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+TBP	B-GENE
+)	O
+plays	O
+an	O
+essential	O
+role	O
+in	O
+transcription	O
+by	O
+all	O
+three	O
+eukaryotic	O
+nuclear	B-GENE
+RNA	I-GENE
+polymerases	I-GENE
+,	O
+polymerases	B-GENE
+(	I-GENE
+Pol	I-GENE
+)	I-GENE
+I	I-GENE
+,	I-GENE
+II	I-GENE
+,	I-GENE
+and	I-GENE
+III	I-GENE
+.	O
+
+A	O
+triple	B-GENE
+-	I-GENE
+mutant	I-GENE
+TBP	I-GENE
+(	O
+R231E	O
++	O
+R235E	O
++	O
+R239S	O
+)	O
+had	O
+greatly	O
+reduced	O
+activity	O
+for	O
+yeast	B-GENE
+U6	I-GENE
+snRNA	I-GENE
+gene	I-GENE
+transcription	O
+while	O
+remaining	O
+active	O
+for	O
+Pol	B-GENE
+II	I-GENE
+basal	O
+transcription	O
+.	O
+
+E2F	B-GENE
+activity	O
+is	O
+regulated	O
+in	O
+part	O
+by	O
+the	O
+retinoblastoma	B-GENE
+family	I-GENE
+of	I-GENE
+tumor	I-GENE
+suppressor	I-GENE
+proteins	I-GENE
+.	O
+
+This	O
+resulted	O
+in	O
+a	O
+complete	O
+inhibition	O
+of	O
+Site	O
+-	O
+1	O
+cleavage	O
+that	O
+was	O
+restored	O
+by	O
+concomitant	O
+overexpression	O
+of	O
+full	O
+-	O
+length	O
+SCAP	B-GENE
+.	O
+
+To	O
+determine	O
+the	O
+true	O
+molecular	O
+identity	O
+of	O
+SFD	B-GENE
+,	O
+both	O
+the	O
+50	O
+-	O
+and	O
+57	O
+-	O
+kDa	O
+polypeptides	O
+were	O
+directly	O
+sequenced	O
+.	O
+
+Molecular	O
+characterization	O
+of	O
+the	O
+50	O
+-	O
+and	O
+57	O
+-	O
+kDa	O
+subunits	O
+of	O
+the	O
+bovine	B-GENE
+vacuolar	I-GENE
+proton	I-GENE
+pump	I-GENE
+.	O
+
+In	O
+C	O
+.	O
+albicans	O
+,	O
+HST6	B-GENE
+is	O
+expressed	O
+constitutively	O
+at	O
+high	O
+levels	O
+in	O
+the	O
+different	O
+cell	O
+types	O
+analysed	O
+(	O
+yeast	O
+,	O
+hyphae	O
+,	O
+white	O
+and	O
+opaque	O
+)	O
+,	O
+demonstrating	O
+that	O
+HST6	B-GENE
+transcription	O
+is	O
+not	O
+repressed	O
+in	O
+this	O
+diploid	O
+yeast	O
+,	O
+unlike	O
+in	O
+diploid	O
+S	O
+.	O
+cerevisiae	O
+,	O
+and	O
+suggesting	O
+a	O
+basic	O
+biological	O
+function	O
+for	O
+the	O
+Hst6p	B-GENE
+transporter	O
+in	O
+C	O
+.	O
+albicans	O
+.	O
+
+Furthermore	O
+,	O
+binding	O
+of	O
+recombinant	B-GENE
+Myb	I-GENE
+and	O
+Ets	B-GENE
+-	I-GENE
+2	I-GENE
+protein	I-GENE
+to	O
+these	O
+fragments	O
+could	O
+be	O
+competed	O
+with	O
+an	O
+excess	O
+of	O
+double	O
+stranded	O
+oligodeoxynucleotides	O
+containing	O
+canonical	O
+,	O
+but	O
+not	O
+mutated	O
+,	O
+Myb	B-GENE
+-	O
+or	O
+Ets	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+This	O
+structure	O
+interconnects	O
+specific	O
+triplets	O
+of	O
+the	O
+basal	O
+bodies	O
+with	O
+the	O
+microtubular	O
+bundles	O
+that	O
+emerge	O
+from	O
+the	O
+basal	O
+apparatus	O
+.	O
+
+To	O
+understand	O
+the	O
+regulatory	O
+mechanism	O
+controlling	O
+its	O
+expression	O
+at	O
+low	O
+temperature	O
+,	O
+the	O
+promoter	O
+region	O
+has	O
+been	O
+characterized	O
+.	O
+
+In	O
+the	O
+current	O
+study	O
+,	O
+the	O
+roles	O
+of	O
+two	O
+putative	O
+cis	O
+-	O
+acting	O
+elements	O
+within	O
+the	O
+-	O
+73	O
+to	O
++	O
+44	O
+region	O
+in	O
+basal	O
+exon	O
+2	O
+promoter	O
+activity	O
+were	O
+evaluated	O
+using	O
+mutagenesis	O
+and	O
+nuclear	O
+protein	O
+-	O
+DNA	O
+binding	O
+assays	O
+.	O
+
+We	O
+have	O
+examined	O
+reporter	O
+gene	O
+(	O
+beta	B-GENE
+-	I-GENE
+gal	I-GENE
+)	O
+expression	O
+directed	O
+by	O
+human	B-GENE
+heat	I-GENE
+shock	I-GENE
+transcription	I-GENE
+factors	I-GENE
+1	I-GENE
+and	I-GENE
+2	I-GENE
+(	O
+HSF1	B-GENE
+and	O
+HSF2	B-GENE
+)	O
+in	O
+HeLa	O
+cells	O
+and	O
+in	O
+yeast	O
+(	O
+Saccharomyces	O
+cerevisiae	O
+)	O
+.	O
+
+Localized	O
+fluorescence	O
+was	O
+detectable	O
+only	O
+in	O
+cells	O
+containing	O
+a	O
+visible	O
+midcell	O
+constriction	O
+,	O
+suggesting	O
+that	O
+FtsK	B-GENE
+targeting	O
+normally	O
+occurs	O
+only	O
+at	O
+a	O
+late	O
+stage	O
+of	O
+septation	O
+.	O
+
+No	O
+TATA	O
+box	O
+was	O
+found	O
+in	O
+the	O
+putative	O
+promoter	O
+region	O
+,	O
+but	O
+multiple	O
+GC	O
+boxes	O
+were	O
+found	O
+around	O
+the	O
+cap	O
+sites	O
+,	O
+supporting	O
+the	O
+previously	O
+inferred	O
+housekeeping	O
+nature	O
+of	O
+CYP51	B-GENE
+gene	I-GENE
+and	O
+the	O
+existence	O
+of	O
+the	O
+multiple	O
+transcription	O
+initiation	O
+sites	O
+.	O
+
+Structural	O
+and	O
+evolutionary	O
+studies	O
+on	O
+sterol	B-GENE
+14	I-GENE
+-	I-GENE
+demethylase	I-GENE
+P450	I-GENE
+(	O
+CYP51	B-GENE
+)	O
+,	O
+the	O
+most	O
+conserved	O
+P450	B-GENE
+monooxygenase	I-GENE
+:	O
+I	O
+.	O
+
+Its	O
+expression	O
+pattern	O
+is	O
+representative	O
+of	O
+many	O
+B	O
+cell	O
+-	O
+specific	O
+proteins	O
+,	O
+which	O
+are	O
+essential	O
+for	O
+B	O
+cell	O
+development	O
+and	O
+activation	O
+but	O
+are	O
+down	O
+-	O
+regulated	O
+after	O
+B	O
+cells	O
+become	O
+terminally	O
+differentiated	O
+plasma	O
+cells	O
+.	O
+
+The	O
+intercistronic	O
+gene	O
+junctions	O
+of	O
+vesicular	O
+stomatitis	O
+virus	O
+(	O
+VSV	O
+)	O
+contain	O
+conserved	O
+sequence	O
+elements	O
+that	O
+are	O
+important	O
+for	O
+polyadenylation	O
+and	O
+transcription	O
+termination	O
+of	O
+upstream	O
+transcript	O
+as	O
+well	O
+as	O
+reinitiation	O
+of	O
+transcription	O
+of	O
+downstream	O
+transcript	O
+.	O
+
+Infectious	O
+mutant	O
+virus	O
+progeny	O
+was	O
+obtained	O
+only	O
+on	O
+complementing	O
+gK	B-GENE
+-	O
+expressing	O
+cells	O
+,	O
+suggesting	O
+that	O
+gK	B-GENE
+has	O
+an	O
+important	O
+function	O
+in	O
+the	O
+replication	O
+cycle	O
+.	O
+
+Cleavage	O
+and	O
+DNA	O
+joining	O
+reactions	O
+,	O
+carried	O
+out	O
+by	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+integrase	I-GENE
+,	O
+are	O
+necessary	O
+to	O
+effect	O
+the	O
+covalent	O
+insertion	O
+of	O
+HIV	O
+-	O
+1	O
+DNA	O
+into	O
+the	O
+host	O
+genome	O
+.	O
+
+The	O
+DSF	O
+regimen	O
+appears	O
+to	O
+have	O
+significant	O
+activity	O
+in	O
+patients	O
+who	O
+have	O
+metastatic	O
+pancreatic	O
+islet	O
+-	O
+cell	O
+carcinoma	O
+,	O
+and	O
+patient	O
+tolerance	O
+of	O
+the	O
+regimen	O
+is	O
+excellent	O
+,	O
+thus	O
+warranting	O
+further	O
+investigation	O
+.	O
+
+Activation	O
+of	O
+the	O
+mitogen	B-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinase	I-GENE
+is	O
+a	O
+primary	O
+consequence	O
+of	O
+Ras	B-GENE
+activation	O
+and	O
+plays	O
+a	O
+key	O
+role	O
+in	O
+mediating	O
+Ras	B-GENE
+signal	O
+transduction	O
+.	O
+
+Histone	B-GENE
+acetylation	O
+levels	O
+in	O
+cells	O
+result	O
+from	O
+a	O
+dynamic	O
+equilibrium	O
+between	O
+competing	O
+histone	B-GENE
+acetylases	I-GENE
+and	I-GENE
+deacetylases	I-GENE
+.	O
+
+CyIIa	B-GENE
+transcription	O
+follows	O
+,	O
+and	O
+is	O
+therefore	O
+downstream	O
+of	O
+,	O
+the	O
+initial	O
+specification	O
+of	O
+these	O
+embryonic	O
+domains	O
+.	O
+
+Cis	O
+-	O
+regulation	O
+downstream	O
+of	O
+cell	O
+type	O
+specification	O
+:	O
+a	O
+single	O
+compact	O
+element	O
+controls	O
+the	O
+complex	O
+expression	O
+of	O
+the	O
+CyIIa	B-GENE
+gene	I-GENE
+in	O
+sea	O
+urchin	O
+embryos	O
+.	O
+
+We	O
+also	O
+present	O
+evidence	O
+that	O
+human	B-GENE
+HYAL1	I-GENE
+is	O
+identical	O
+to	O
+an	O
+uncharacterized	O
+gene	O
+positionally	O
+cloned	O
+by	O
+others	O
+from	O
+chromosome	O
+3p21	O
+.	O
+3	O
+that	O
+is	O
+homozygously	O
+deleted	O
+in	O
+several	O
+small	O
+-	O
+cell	O
+lung	O
+carcinoma	O
+cell	O
+lines	O
+.	O
+
+In	O
+patients	O
+with	O
+myalgia	O
+,	O
+Raynaud	O
+'	O
+s	O
+syndrome	O
+,	O
+skin	O
+vasculitis	O
+and	O
+vascular	O
+diseases	O
+WFAg	B-GENE
+concentrations	O
+were	O
+higher	O
+than	O
+in	O
+patients	O
+without	O
+them	O
+.	O
+
+Although	O
+the	O
+expression	O
+of	O
+the	O
+4E	B-GENE
+-	I-GENE
+BP1	I-GENE
+gene	I-GENE
+alone	O
+has	O
+not	O
+yet	O
+been	O
+accomplished	O
+,	O
+the	O
+gene	O
+was	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+[	O
+BL21	O
+(	O
+DE3	O
+)	O
+]	O
+as	O
+a	O
+fusion	O
+gene	O
+with	O
+the	O
+glutathione	B-GENE
+-	I-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+(	O
+GST	B-GENE
+)	O
+gene	O
+using	O
+a	O
+prokaryotic	O
+gene	O
+fusion	O
+vector	O
+(	O
+pGEX	O
+-	O
+4T	O
+-	O
+2	O
+)	O
+,	O
+which	O
+contains	O
+a	O
+gene	O
+sequence	O
+coding	O
+the	O
+cleavage	O
+site	O
+for	O
+a	O
+specific	O
+protease	O
+,	O
+alpha	B-GENE
+-	I-GENE
+thrombin	I-GENE
+.	O
+
+Randomised	O
+comparison	O
+of	O
+addition	O
+of	O
+autologous	O
+bone	O
+-	O
+marrow	O
+transplantation	O
+to	O
+intensive	O
+chemotherapy	O
+for	O
+acute	O
+myeloid	O
+leukaemia	O
+in	O
+first	O
+remission	O
+:	O
+results	O
+of	O
+MRC	O
+AML	O
+10	O
+trial	O
+.	O
+
+Therapeutic	O
+use	O
+of	O
+cannabis	O
+.	O
+
+Analysis	O
+of	O
+intragenic	O
+revertants	O
+shows	O
+that	O
+this	O
+function	O
+depends	O
+on	O
+the	O
+amino	O
+acid	O
+preceding	O
+the	O
+first	O
+cysteine	O
+residue	O
+of	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+Hap1p	B-GENE
+.	O
+
+Peripheral	O
+visual	O
+stimuli	O
+and	O
+monoaural	O
+auditory	O
+stimuli	O
+were	O
+used	O
+as	O
+targets	O
+.	O
+
+A	O
+review	O
+of	O
+studies	O
+published	O
+between	O
+1983	O
+and	O
+1995	O
+shows	O
+that	O
+there	O
+are	O
+some	O
+common	O
+factors	O
+as	O
+regards	O
+the	O
+psychological	O
+distress	O
+and	O
+social	O
+and	O
+functional	O
+limitations	O
+this	O
+group	O
+of	O
+patients	O
+has	O
+to	O
+deal	O
+with	O
+.	O
+
+PKC	B-GENE
+-	I-GENE
+gamma	I-GENE
+,	O
+which	O
+is	O
+not	O
+present	O
+in	O
+keratinocytes	O
+,	O
+also	O
+induces	O
+involucrin	B-GENE
+gene	I-GENE
+expression	O
+in	O
+a	O
+TPA	O
+-	O
+independent	O
+manner	O
+,	O
+when	O
+introduced	O
+into	O
+SVHK	O
+cells	O
+.	O
+
+Identification	O
+and	O
+characterization	O
+of	O
+specific	O
+DNA	O
+-	O
+binding	O
+complexes	O
+containing	O
+members	O
+of	O
+the	O
+Myc	B-GENE
+/	O
+Max	B-GENE
+/	O
+Mad	B-GENE
+network	O
+of	O
+transcriptional	O
+regulators	O
+.	O
+
+We	O
+further	O
+show	O
+that	O
+proteolytic	O
+targeting	O
+by	O
+calpain	B-GENE
+II	I-GENE
+and	O
+the	O
+proteasome	O
+involves	O
+different	O
+structural	O
+elements	O
+of	O
+YY1	B-GENE
+.	O
+
+Primers	O
+for	O
+subsequent	O
+rounds	O
+of	O
+RACE	O
+were	O
+designed	O
+from	O
+the	O
+5	O
+'	O
+-	O
+ends	O
+of	O
+amplified	O
+RACE	O
+products	O
+.	O
+
+Human	O
+ZFM1	B-GENE
+protein	I-GENE
+is	O
+a	O
+transcriptional	O
+repressor	O
+that	O
+interacts	O
+with	O
+the	O
+transcription	B-GENE
+activation	I-GENE
+domain	I-GENE
+of	I-GENE
+stage	I-GENE
+-	I-GENE
+specific	I-GENE
+activator	I-GENE
+protein	I-GENE
+.	O
+
+Surprisingly	O
+,	O
+the	O
+CSF1R	B-GENE
+/	O
+IRDelta960	B-GENE
+was	O
+as	O
+effective	O
+as	O
+the	O
+CSF1R	B-GENE
+/	O
+IR	B-GENE
+in	O
+mediating	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+protection	O
+of	O
+cells	O
+from	O
+staurosporine	O
+-	O
+induced	O
+apoptosis	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+special	O
+clinical	O
+presentation	O
+of	O
+our	O
+case	O
+of	O
+possible	O
+Gardner	O
+'	O
+s	O
+syndrome	O
+is	O
+discussed	O
+.	O
+
+These	O
+results	O
+would	O
+suggest	O
+that	O
+a	O
+high	O
+UV	O
+sensitivity	O
+is	O
+associated	O
+with	O
+high	O
+phaeomelanin	O
+and	O
+low	O
+eumelanin	O
+levels	O
+,	O
+and	O
+point	O
+to	O
+the	O
+eumelanin	O
+/	O
+phaeomelanin	O
+ratio	O
+as	O
+a	O
+novel	O
+chemical	O
+parameter	O
+that	O
+could	O
+be	O
+used	O
+for	O
+predicting	O
+individuals	O
+at	O
+high	O
+risk	O
+for	O
+skin	O
+cancer	O
+and	O
+melanoma	O
+.	O
+
+In	O
+ferrets	O
+naturally	O
+infected	O
+with	O
+H	O
+.	O
+mustelae	O
+,	O
+a	O
+single	O
+dose	O
+(	O
+50	O
+mg	O
+/	O
+kg	O
+,	O
+per	O
+os	O
+)	O
+of	O
+fluorofamide	O
+completely	O
+inhibited	O
+bacterial	B-GENE
+urease	I-GENE
+.	O
+
+The	O
+cAMP	O
+-	O
+dependent	O
+mitogenic	O
+pathway	O
+is	O
+unique	O
+as	O
+it	O
+is	O
+independent	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+activation	O
+and	O
+differs	O
+from	O
+growth	O
+factor	O
+-	O
+dependent	O
+pathways	O
+at	O
+the	O
+level	O
+of	O
+the	O
+expression	O
+of	O
+several	O
+protooncogenes	O
+/	O
+transcription	O
+factors	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Use	O
+of	O
+the	O
+first	O
+method	O
+was	O
+associated	O
+with	O
+a	O
+reduction	O
+in	O
+the	O
+time	O
+patients	O
+remained	O
+in	O
+the	O
+ICU	O
+before	O
+transfer	O
+to	O
+another	O
+unit	O
+and	O
+savings	O
+in	O
+nursing	O
+time	O
+,	O
+but	O
+the	O
+two	O
+methods	O
+did	O
+not	O
+differ	O
+according	O
+to	O
+clinical	O
+outcomes	O
+.	O
+
+We	O
+have	O
+elucidated	O
+the	O
+exon	O
+-	O
+intron	O
+organization	O
+of	O
+the	O
+entire	O
+human	O
+CD58	B-GENE
+gene	I-GENE
+,	O
+including	O
+approximately	O
+2	O
+.	O
+5	O
+kilobases	O
+(	O
+kb	O
+)	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+DNA	O
+.	O
+
+The	O
+risk	O
+factors	O
+for	O
+hematuria	O
+in	O
+patients	O
+with	O
+renal	O
+hypouricemia	O
+are	O
+the	O
+elevation	O
+of	O
+urinary	O
+urate	O
+concentration	O
+and	O
+the	O
+subtypes	O
+of	O
+Post	O
+and	O
+Secretion	O
+.	O
+
+Two	O
+hundred	O
+sixty	O
+-	O
+four	O
+patients	O
+scheduled	O
+for	O
+DCBM	O
+were	O
+randomized	O
+to	O
+receive	O
+intravenously	O
+geG	O
+0	O
+.	O
+25	O
+mg	O
+(	O
+geG	O
+-	O
+25	O
+)	O
+,	O
+or	O
+geG	O
+0	O
+.	O
+5	O
+mg	O
+(	O
+geG	O
+-	O
+50	O
+)	O
+,	O
+or	O
+HBB	O
+20	O
+mg	O
+as	O
+hypotonic	O
+agent	O
+.	O
+
+If	O
+the	O
+haemoglobin	B-GENE
+concentration	O
+(	O
+Hb	B-GENE
+)	O
+was	O
+less	O
+than	O
+12	O
+g	O
+dL	O
+-	O
+1	O
+they	O
+were	O
+given	O
+a	O
+four	O
+week	O
+course	O
+of	O
+ferrous	O
+sulphate	O
+.	O
+
+Based	O
+on	O
+restriction	O
+enzyme	O
+analysis	O
+,	O
+Southern	O
+blots	O
+,	O
+polymerase	O
+chain	O
+reaction	O
+analysis	O
+and	O
+DNA	O
+sequencing	O
+,	O
+it	O
+was	O
+confirmed	O
+that	O
+the	O
+three	O
+overlapping	O
+clones	O
+isolated	O
+cover	O
+the	O
+entire	O
+cHO	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+,	O
+as	O
+well	O
+as	O
+approximately	O
+10	O
+kb	O
+of	O
+the	O
+flanking	O
+regions	O
+on	O
+both	O
+ends	O
+.	O
+
+Position	O
+-	O
+independent	O
+expression	O
+of	O
+a	O
+human	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	O
+luciferase	B-GENE
+reporter	O
+gene	O
+cloned	O
+on	O
+a	O
+yeast	O
+artificial	O
+chromosome	O
+vector	O
+.	O
+
+Calcitriol	O
+therapy	O
+was	O
+associated	O
+with	O
+a	O
+decrease	O
+in	O
+serum	O
+iPTH	B-GENE
+levels	O
+(	O
+701	O
++	O
+/	O
+-	O
+103	O
+.	O
+9	O
+vs	O
+.	O
+
+Alterations	O
+in	O
+DNase	B-GENE
+I	I-GENE
+reactivity	O
+of	O
+the	O
+GC	O
+-	O
+response	O
+element	O
+region	O
+suggest	O
+that	O
+GC	B-GENE
+receptor	I-GENE
+-	I-GENE
+GC	I-GENE
+complexes	I-GENE
+may	O
+associate	O
+,	O
+in	O
+a	O
+transient	O
+manner	O
+,	O
+with	O
+the	O
+promoter	O
+in	O
+the	O
+actively	O
+transcribing	O
+control	O
+state	O
+.	O
+
+Most	O
+pituitary	O
+hormone	O
+-	O
+coding	O
+gene	O
+promoters	O
+are	O
+activated	O
+by	O
+Ptx1	B-GENE
+.	O
+
+One	O
+of	O
+these	O
+small	B-GENE
+inteins	I-GENE
+might	O
+be	O
+inactive	O
+or	O
+a	O
+"	B-GENE
+pseudo	I-GENE
+intein	I-GENE
+.	I-GENE
+"	I-GENE
+The	O
+results	O
+suggest	O
+a	O
+modular	O
+architecture	O
+for	O
+inteins	B-GENE
+,	O
+clarify	O
+their	O
+origin	O
+and	O
+relationship	O
+to	O
+other	O
+protein	O
+families	O
+,	O
+and	O
+extend	O
+recent	O
+experimental	O
+findings	O
+on	O
+the	O
+functional	O
+roles	O
+of	O
+intein	B-GENE
+N	I-GENE
+,	I-GENE
+C	I-GENE
+,	I-GENE
+and	I-GENE
+EN	I-GENE
+motifs	I-GENE
+.	O
+
+Purification	O
+of	O
+MvaT	B-GENE
+enriched	O
+for	O
+two	O
+polypeptides	O
+of	O
+approximate	O
+molecular	O
+mass	O
+15	O
+kDa	O
+and	O
+16	O
+kDa	O
+,	O
+designated	O
+P15	B-GENE
+and	O
+P16	B-GENE
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+TGF	B-GENE
+-	I-GENE
+betaf	I-GENE
+potentiates	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+SRE	O
+activated	O
+by	O
+PKC	B-GENE
+through	O
+the	O
+SRF	B-GENE
+binding	I-GENE
+site	I-GENE
+.	O
+
+BACKGROUND	O
+:	O
+Defensins	B-GENE
+,	O
+also	O
+known	O
+as	O
+human	B-GENE
+neutrophil	I-GENE
+peptides	I-GENE
+,	O
+are	O
+antimicrobial	O
+peptides	O
+present	O
+in	O
+the	O
+azurophil	O
+granules	O
+of	O
+neutrophils	O
+.	O
+
+The	O
+spontaneous	O
+mutation	O
+blocking	O
+pca	B-GENE
+gene	I-GENE
+expression	O
+was	O
+located	O
+in	O
+the	O
+promoter	O
+for	O
+the	O
+pca	B-GENE
+operon	I-GENE
+.	O
+
+From	O
+250	O
+g	O
+of	O
+cells	O
+,	O
+we	O
+isolated	O
+1	O
+mg	O
+of	O
+PDH	B-GENE
+complex	I-GENE
+with	O
+a	O
+specific	O
+activity	O
+of	O
+12	O
+.	O
+6	O
+U	O
+/	O
+mg	O
+of	O
+protein	O
+.	O
+
+The	O
+PDH	B-GENE
+complex	I-GENE
+-	I-GENE
+encoding	I-GENE
+genes	I-GENE
+were	O
+identified	O
+by	O
+hybridization	O
+experiments	O
+and	O
+sequence	O
+analysis	O
+in	O
+two	O
+separate	O
+gene	O
+regions	O
+in	O
+the	O
+genome	O
+of	O
+Z	O
+.	O
+mobilis	O
+.	O
+
+We	O
+have	O
+identified	O
+two	O
+functional	O
+elements	O
+,	O
+both	O
+located	O
+downstream	O
+from	O
+the	O
+TATA	O
+motif	O
+,	O
+that	O
+control	O
+Id4	B-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+Azithromycin	O
+is	O
+a	O
+new	O
+generation	O
+macrolide	O
+antibiotic	O
+with	O
+unusual	O
+and	O
+favorable	O
+pharmacokinetics	O
+,	O
+and	O
+seems	O
+to	O
+be	O
+a	O
+very	O
+promising	O
+agent	O
+for	O
+innovative	O
+anti	O
+-	O
+H	O
+.	O
+pylori	O
+regimens	O
+.	O
+
+The	O
+study	O
+enrolled	O
+994	O
+people	O
+co	O
+-	O
+infected	O
+with	O
+CMV	O
+and	O
+HIV	O
+,	O
+with	O
+at	O
+least	O
+one	O
+CD4	B-GENE
+count	O
+recorded	O
+<	O
+100	O
+x	O
+10	O
+(	O
+6	O
+)	O
+cells	O
+/	O
+l	O
+.	O
+
+National	O
+certification	O
+:	O
+a	O
+vital	O
+component	O
+of	O
+quality	O
+assurance	O
+.	O
+
+Two	O
+rare	O
+novel	O
+mutations	O
+,	O
+D811N	O
+in	O
+exon	O
+20	O
+and	O
+R835C	O
+in	O
+exon	O
+21	O
+,	O
+were	O
+identified	O
+in	O
+the	O
+first	O
+nucleotide	O
+-	O
+binding	O
+fold	O
+(	O
+NBF	O
+)	O
+,	O
+a	O
+functionally	O
+important	O
+region	O
+of	O
+SUR1	B-GENE
+,	O
+in	O
+one	O
+patient	O
+each	O
+,	O
+both	O
+heterozygotes	O
+.	O
+
+Chimaeric	O
+VP16	B-GENE
+-	O
+E2	B-GENE
+molecules	O
+suggest	O
+that	O
+the	O
+epithelial	O
+specific	O
+transcriptional	O
+activation	O
+of	O
+the	O
+BPV	B-GENE
+-	I-GENE
+4	I-GENE
+LCR	I-GENE
+promoter	I-GENE
+is	O
+mediated	O
+by	O
+the	O
+E2	B-GENE
+transactivation	I-GENE
+domain	I-GENE
+.	O
+
+These	O
+changes	O
+correlate	O
+directly	O
+with	O
+an	O
+increase	O
+in	O
+the	O
+acetylation	O
+levels	O
+of	O
+all	O
+four	O
+core	B-GENE
+histones	I-GENE
+in	O
+vivo	O
+.	O
+
+Drosophila	B-GENE
+orthodenticle	I-GENE
+(	O
+otd	B-GENE
+)	O
+and	O
+murine	B-GENE
+Otx	I-GENE
+genes	I-GENE
+exemplify	O
+this	O
+,	O
+both	O
+in	O
+terms	O
+of	O
+expression	O
+patterns	O
+and	O
+mutant	O
+phenotypes	O
+.	O
+
+APETALA3	B-GENE
+transcripts	I-GENE
+are	O
+first	O
+detected	O
+in	O
+a	O
+meristematic	O
+region	O
+that	O
+will	O
+give	O
+rise	O
+to	O
+the	O
+petal	O
+and	O
+stamen	O
+primordia	O
+,	O
+and	O
+expression	O
+is	O
+maintained	O
+in	O
+this	O
+region	O
+during	O
+subsequent	O
+development	O
+of	O
+these	O
+organs	O
+.	O
+
+We	O
+also	O
+recovered	O
+mutations	O
+in	O
+the	O
+60A	B-GENE
+gene	I-GENE
+which	O
+encodes	O
+another	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+related	I-GENE
+factor	I-GENE
+in	O
+Drosophila	O
+.	O
+
+Cell	O
+lines	O
+are	O
+checked	O
+to	O
+find	O
+out	O
+whether	O
+they	O
+develop	O
+tumors	O
+in	O
+nude	O
+mice	O
+followed	O
+by	O
+an	O
+analysis	O
+of	O
+the	O
+karyotype	O
+.	O
+
+Cervicovaginal	O
+foetal	B-GENE
+fibronectin	I-GENE
+in	O
+the	O
+prediction	O
+of	O
+preterm	O
+labour	O
+in	O
+a	O
+low	O
+-	O
+risk	O
+population	O
+.	O
+
+In	O
+addition	O
+,	O
+IgM	B-GENE
+can	O
+be	O
+absent	O
+in	O
+children	O
+with	O
+congenital	O
+toxoplasmosis	O
+or	O
+subjects	O
+with	O
+secondary	O
+reactivation	O
+.	O
+
+Both	O
+variants	O
+display	O
+the	O
+seven	O
+-	O
+transmembrane	O
+topology	O
+that	O
+is	O
+typical	O
+for	O
+G	B-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+receptors	I-GENE
+.	O
+
+A	O
+constitutive	O
+allele	O
+of	O
+GPA2	B-GENE
+could	O
+stimulate	O
+growth	O
+of	O
+a	O
+strain	O
+lacking	O
+both	O
+RAS	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+COOH	O
+-	O
+terminus	O
+of	O
+this	O
+new	O
+isoform	O
+,	O
+which	O
+we	O
+designate	O
+beta	B-GENE
+4	I-GENE
+,	O
+lacks	O
+a	O
+22	O
+amino	O
+acid	O
+lysine	O
+-	O
+rich	O
+sequence	O
+common	O
+to	O
+both	O
+the	O
+human	B-GENE
+red	I-GENE
+cell	I-GENE
+alpha	I-GENE
+-	I-GENE
+and	I-GENE
+beta	I-GENE
+-	I-GENE
+adducin	I-GENE
+subunits	I-GENE
+and	O
+homologous	O
+to	O
+a	O
+highly	O
+conserved	O
+region	O
+in	O
+MARCKS	B-GENE
+,	O
+a	O
+filamentous	O
+actin	B-GENE
+-	O
+cross	O
+linking	O
+protein	O
+regulated	O
+by	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+and	O
+calcium	O
+/	O
+calmodulin	B-GENE
+.	O
+beta	B-GENE
+4	I-GENE
+-	I-GENE
+adducin	I-GENE
+preserves	O
+a	O
+previously	O
+identified	O
+calmodulin	B-GENE
+binding	I-GENE
+domain	I-GENE
+.	O
+
+PCR	O
+analysis	O
+indicates	O
+that	O
+this	O
+new	O
+beta	B-GENE
+-	I-GENE
+adducin	I-GENE
+isoform	I-GENE
+is	O
+expressed	O
+in	O
+fetal	O
+brain	O
+and	O
+liver	O
+,	O
+bone	O
+marrow	O
+,	O
+and	O
+NT	O
+-	O
+2	O
+(	O
+neuroepithelial	O
+)	O
+cells	O
+,	O
+but	O
+is	O
+not	O
+detected	O
+in	O
+several	O
+other	O
+tissues	O
+.	O
+
+The	O
+gene	B-GENE
+lac	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+encoding	O
+the	O
+enzyme	O
+laccase	B-GENE
+,	O
+is	O
+the	O
+best	O
+characterized	O
+of	O
+a	O
+number	O
+of	O
+genes	O
+in	O
+the	O
+chestnut	O
+blight	O
+fungus	O
+,	O
+Cryphonectria	O
+parasitica	O
+,	O
+that	O
+are	O
+repressed	O
+by	O
+hypoviruses	O
+,	O
+a	O
+group	O
+of	O
+virulence	O
+-	O
+attenuating	O
+mycoviruses	O
+.	O
+lac	B-GENE
+-	I-GENE
+1	I-GENE
+has	O
+also	O
+been	O
+shown	O
+to	O
+be	O
+transcriptionally	O
+activated	O
+by	O
+low	O
+concentrations	O
+of	O
+the	O
+translational	O
+inhibitor	O
+cycloheximide	O
+(	O
+CHX	O
+)	O
+and	O
+by	O
+the	O
+immunosuppressant	O
+cyclosporin	O
+A	O
+.	O
+
+Both	O
+TRE	O
+-	O
+like	O
+elements	O
+were	O
+capable	O
+of	O
+binding	O
+AP1	B-GENE
+.	O
+
+The	O
+hp55	B-GENE
+gamma	I-GENE
+protein	I-GENE
+interacts	O
+strongly	O
+with	O
+the	O
+activated	O
+IGFIR	B-GENE
+but	O
+not	O
+with	O
+the	O
+kinase	O
+-	O
+negative	O
+mutant	O
+receptor	O
+.	O
+hp55	B-GENE
+gamma	I-GENE
+also	O
+interacts	O
+with	O
+the	O
+insulin	B-GENE
+receptor	I-GENE
+(	O
+IR	B-GENE
+)	O
+in	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+.	O
+
+The	O
+plant	O
+protein	O
+maintains	O
+all	O
+the	O
+functional	O
+domains	O
+found	O
+in	O
+the	O
+other	O
+proteins	O
+,	O
+including	O
+nuclear	O
+localization	O
+signal	O
+,	O
+DNA	O
+-	O
+binding	O
+domain	O
+and	O
+helicase	B-GENE
+motifs	I-GENE
+,	O
+suggesting	O
+that	O
+it	O
+might	O
+also	O
+act	O
+as	O
+part	O
+of	O
+the	O
+RNA	O
+transcription	O
+apparatus	O
+,	O
+as	O
+well	O
+as	O
+nucleotide	O
+excision	O
+repair	O
+in	O
+plant	O
+cells	O
+.	O
+
+This	O
+paper	O
+describes	O
+the	O
+genomic	O
+organization	O
+of	O
+mouse	O
+gC1qBP	B-GENE
+and	O
+the	O
+characterization	O
+of	O
+its	O
+5	O
+'	O
+flanking	O
+region	O
+.	O
+
+LysR	B-GENE
+proteins	I-GENE
+have	O
+been	O
+shown	O
+to	O
+regulate	O
+urease	B-GENE
+in	I-GENE
+Klebsiella	I-GENE
+aerogenes	I-GENE
+(	O
+NAC	B-GENE
+)	O
+,	O
+and	O
+catalase	B-GENE
+in	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+(	O
+OxyR	B-GENE
+)	O
+,	O
+which	O
+offers	O
+the	O
+intracellular	O
+bacterium	O
+protection	O
+from	O
+phagolysosome	O
+damage	O
+.	O
+
+Also	O
+,	O
+the	O
+anti	O
+-	O
+inflammatory	O
+activities	O
+of	O
+an	O
+aqueous	O
+extract	O
+of	O
+Buddleia	O
+cordata	O
+and	O
+its	O
+principal	O
+glycoside	O
+linarin	O
+were	O
+evaluated	O
+.	O
+
+Regulation	O
+of	O
+the	O
+Raf	B-GENE
+kinase	I-GENE
+in	O
+T	O
+cells	O
+differs	O
+from	O
+findings	O
+with	O
+a	O
+variety	O
+of	O
+cell	O
+lines	O
+that	O
+the	O
+catalytic	B-GENE
+domain	I-GENE
+of	I-GENE
+Raf	I-GENE
+(	O
+Raf	B-GENE
+(	O
+delta26	O
+-	O
+303	O
+)	O
+)	O
+shows	O
+no	O
+activity	O
+.	O
+
+Full	B-GENE
+-	I-GENE
+length	I-GENE
+FLAP	I-GENE
+clones	O
+were	O
+isolated	O
+from	O
+a	O
+mouse	O
+skeletal	O
+muscle	O
+cDNA	O
+library	O
+.	O
+
+We	O
+have	O
+visualized	O
+DNA	O
+-	O
+protein	O
+complexes	O
+by	O
+electron	O
+microscopy	O
+and	O
+a	O
+high	O
+-	O
+affinity	O
+binding	O
+site	O
+of	O
+WDV	B-GENE
+Rep	I-GENE
+protein	I-GENE
+within	O
+the	O
+core	O
+element	O
+has	O
+been	O
+mapped	O
+to	O
+approximately	O
+144	O
++	O
+/	O
+-	O
+18	O
+bp	O
+upstream	O
+from	O
+the	O
+initiation	O
+site	O
+,	O
+between	O
+the	O
+start	O
+site	O
+for	O
+complementary	O
+-	O
+sense	O
+transcription	O
+and	O
+the	O
+TATA	O
+box	O
+.	O
+
+Rex	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+a	O
+gene	O
+encoding	O
+a	O
+transcription	O
+factor	O
+expressed	O
+in	O
+the	O
+early	O
+embryo	O
+,	O
+is	O
+regulated	O
+via	O
+Oct	B-GENE
+-	I-GENE
+3	I-GENE
+/	I-GENE
+4	I-GENE
+and	O
+Oct	B-GENE
+-	I-GENE
+6	I-GENE
+binding	O
+to	O
+an	O
+octamer	O
+site	O
+and	O
+a	O
+novel	O
+protein	O
+,	O
+Rox	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+binding	O
+to	O
+an	O
+adjacent	O
+site	O
+.	O
+
+However	O
+,	O
+inhibition	O
+of	O
+both	O
+the	O
+ERK	B-GENE
+/	O
+RSK	B-GENE
+and	O
+the	O
+p38	B-GENE
+/	O
+MAPKAP	B-GENE
+kinase	I-GENE
+2	I-GENE
+pathways	O
+completely	O
+abolished	O
+NGF	B-GENE
+-	O
+induced	O
+CREB	B-GENE
+Ser	O
+-	O
+133	O
+phosphorylation	O
+.	O
+
+Cells	O
+respond	O
+to	O
+the	O
+accumulation	O
+of	O
+unfolded	O
+proteins	O
+in	O
+the	O
+endoplasmic	O
+reticulum	O
+(	O
+ER	O
+)	O
+by	O
+increasing	O
+the	O
+transcription	O
+of	O
+the	O
+genes	O
+encoding	O
+ER	B-GENE
+-	I-GENE
+resident	I-GENE
+chaperone	I-GENE
+proteins	I-GENE
+.	O
+
+The	O
+mei4	B-GENE
++	I-GENE
+gene	I-GENE
+of	O
+the	O
+fission	O
+yeast	O
+Schizosaccharomyces	O
+pombe	O
+was	O
+cloned	O
+by	O
+functional	O
+complementation	O
+.	O
+
+In	O
+some	O
+cases	O
+,	O
+the	O
+aberrant	O
+methylation	O
+of	O
+CpGs	O
+within	O
+5	O
+'	O
+regulatory	O
+regions	O
+has	O
+led	O
+to	O
+suppression	O
+of	O
+gene	O
+activity	O
+.	O
+
+The	O
+genomic	O
+fragments	O
+were	O
+fused	O
+upstream	O
+of	O
+the	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+.	O
+
+Cotransfection	O
+analyses	O
+of	O
+the	O
+T	B-GENE
+/	I-GENE
+EBP	I-GENE
+promoter	I-GENE
+-	I-GENE
+reporter	I-GENE
+constructs	I-GENE
+with	O
+a	O
+T	B-GENE
+/	I-GENE
+EBP	I-GENE
+expression	O
+vector	O
+into	O
+human	O
+HepG2	O
+cells	O
+,	O
+which	O
+do	O
+not	O
+express	O
+T	B-GENE
+/	I-GENE
+EBP	I-GENE
+,	O
+suggested	O
+that	O
+autoregulation	O
+may	O
+be	O
+involved	O
+in	O
+controlling	O
+both	O
+rat	O
+and	O
+human	B-GENE
+T	I-GENE
+/	I-GENE
+EBP	I-GENE
+gene	I-GENE
+expression	O
+.	O
+
+Deletion	O
+of	O
+the	O
+last	O
+two	O
+Ser	O
+residues	O
+,	O
+including	O
+one	O
+PKC	B-GENE
+consensus	O
+site	O
+in	O
+the	O
+receptor	O
+tail	O
+,	O
+prevented	O
+only	O
+phorbol	O
+12	O
+-	O
+myristate	O
+13	O
+-	O
+acetate	O
+-	O
+induced	O
+desensitization	O
+by	O
+30	O
+%	O
+.	O
+
+Flap	O
+survival	O
+depends	O
+on	O
+the	O
+development	O
+of	O
+a	O
+small	O
+number	O
+of	O
+vascular	O
+connections	O
+between	O
+vessels	O
+arising	O
+from	O
+the	O
+pedicle	O
+and	O
+preexisting	O
+dermal	O
+vessels	O
+.	O
+
+Jean	O
+Klig	O
+reviews	O
+recent	O
+literature	O
+about	O
+lower	O
+respiratory	O
+tract	O
+infection	O
+in	O
+children	O
+.	O
+
+Potential	O
+indicators	O
+were	O
+assessed	O
+for	O
+the	O
+two	O
+classifications	O
+of	O
+protein	O
+-	O
+energy	O
+malnutrition	O
+in	O
+the	O
+guidelines	O
+for	O
+integrated	O
+management	O
+of	O
+childhood	O
+illness	O
+:	O
+severe	O
+malnutrition	O
+,	O
+which	O
+requires	O
+immediate	O
+referral	O
+to	O
+hospital	O
+,	O
+and	O
+very	O
+low	O
+weight	O
+,	O
+which	O
+calls	O
+for	O
+feeding	O
+assessment	O
+,	O
+nutritional	O
+counselling	O
+and	O
+follow	O
+-	O
+up	O
+.	O
+
+Despite	O
+its	O
+requirement	O
+for	O
+enhancer	O
+-	O
+dependent	O
+splicing	O
+activity	O
+in	O
+vitro	O
+,	O
+the	O
+dU2AF38	B-GENE
+RS	I-GENE
+domain	I-GENE
+was	O
+also	O
+inessential	O
+in	O
+vivo	O
+.	O
+
+In	O
+vitro	O
+binding	O
+studies	O
+using	O
+GST	B-GENE
+fusion	O
+proteins	O
+and	O
+yeast	O
+extracts	O
+defined	O
+distinct	O
+binding	O
+sites	O
+on	O
+yAP180A	B-GENE
+for	O
+Pan1p	B-GENE
+and	O
+clathrin	B-GENE
+.	O
+yAP180	B-GENE
+proteins	I-GENE
+and	O
+Pan1p	B-GENE
+,	O
+like	O
+actin	B-GENE
+,	O
+localize	O
+to	O
+peripheral	O
+patches	O
+along	O
+the	O
+plasma	O
+membrane	O
+.	O
+
+In	O
+vitro	O
+affinity	O
+analyses	O
+demonstrated	O
+that	O
+recombinant	O
+130	O
+-	O
+kD	O
+protein	O
+directly	O
+interacts	O
+with	O
+ZO	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+the	O
+cytoplasmic	O
+domain	O
+of	O
+occludin	B-GENE
+,	O
+but	O
+not	O
+with	O
+ZO	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+Cytochrome	B-GENE
+b	I-GENE
+in	O
+human	B-GENE
+complex	I-GENE
+II	I-GENE
+(	O
+succinate	B-GENE
+-	I-GENE
+ubiquinone	I-GENE
+oxidoreductase	I-GENE
+)	O
+:	O
+cDNA	O
+cloning	O
+of	O
+the	O
+components	O
+in	O
+liver	O
+mitochondria	O
+and	O
+chromosome	O
+assignment	O
+of	O
+the	O
+genes	O
+for	O
+the	O
+large	O
+(	O
+SDHC	B-GENE
+)	O
+and	O
+small	O
+(	O
+SDHD	B-GENE
+)	O
+subunits	O
+to	O
+1q21	O
+and	O
+11q23	O
+.	O
+
+A	O
+possible	O
+decrease	O
+in	O
+theophylline	O
+'	O
+s	O
+volume	O
+of	O
+distribution	O
+at	O
+4	O
+days	O
+,	O
+but	O
+not	O
+immediately	O
+,	O
+after	O
+administration	O
+of	O
+chloroquine	O
+was	O
+suggested	O
+,	O
+although	O
+this	O
+just	O
+failed	O
+to	O
+achieve	O
+statistical	O
+significance	O
+(	O
+p	O
+=	O
+0	O
+.	O
+055	O
+)	O
+.	O
+
+The	O
+addition	O
+of	O
+a	O
+Paf	B-GENE
+-	O
+containing	O
+extract	O
+does	O
+not	O
+lead	O
+to	O
+significant	O
+protein	O
+binding	O
+to	O
+these	O
+two	O
+hly	B-GENE
+target	I-GENE
+sequences	I-GENE
+in	O
+the	O
+absence	O
+of	O
+PrfA	B-GENE
+but	O
+converts	O
+the	O
+complex	O
+(	O
+CIII	O
+)	O
+consisting	O
+of	O
+PrfA	B-GENE
+and	O
+the	O
+109	B-GENE
+bp	I-GENE
+hly	I-GENE
+DNA	I-GENE
+fragment	I-GENE
+to	O
+a	O
+slower	O
+migrating	O
+PrfA	B-GENE
+-	O
+Paf	B-GENE
+-	O
+DNA	O
+complex	O
+(	O
+CI	O
+)	O
+.	O
+
+ROCK	B-GENE
+-	I-GENE
+I	I-GENE
+,	O
+Kinectin	B-GENE
+,	O
+and	O
+mDia2	B-GENE
+can	O
+bind	O
+the	O
+wild	O
+type	O
+forms	O
+of	O
+both	O
+RhoA	B-GENE
+and	O
+Cdc42	B-GENE
+in	O
+a	O
+GTP	O
+-	O
+dependent	O
+manner	O
+in	O
+vitro	O
+.	O
+
+Among	O
+three	O
+isoforms	O
+,	O
+the	O
+beta	O
+isoform	O
+has	O
+the	O
+greatest	O
+Vmax	O
+value	O
+for	O
+the	O
+PtdIns	B-GENE
+(	I-GENE
+4	I-GENE
+)	I-GENE
+P	I-GENE
+kinase	I-GENE
+activity	O
+and	O
+the	O
+gamma	O
+isoform	O
+is	O
+most	O
+markedly	O
+stimulated	O
+by	O
+phosphatidic	O
+acid	O
+.	O
+
+The	O
+beta	O
+subunit	O
+of	O
+the	O
+heterotrimeric	B-GENE
+G	I-GENE
+proteins	I-GENE
+that	O
+transduce	O
+signals	O
+across	O
+the	O
+plasma	O
+membrane	O
+is	O
+made	O
+up	O
+of	O
+an	O
+amino	O
+-	O
+terminal	O
+alpha	O
+-	O
+helical	O
+segment	O
+followed	O
+by	O
+seven	O
+repeating	O
+units	O
+called	O
+WD	O
+(	O
+Trp	O
+-	O
+Asp	O
+)	O
+repeats	O
+that	O
+occur	O
+in	O
+about	O
+140	O
+different	O
+proteins	O
+.	O
+
+Two	O
+differentially	O
+expressed	O
+LNX	B-GENE
+messages	I-GENE
+encode	O
+overlapping	O
+proteins	O
+with	O
+predicted	O
+molecular	O
+masses	O
+of	O
+80	B-GENE
+kDa	I-GENE
+(	I-GENE
+LNX	I-GENE
+)	I-GENE
+and	O
+70	B-GENE
+kDa	I-GENE
+(	I-GENE
+LNX	I-GENE
+-	I-GENE
+b	I-GENE
+)	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+contractile	O
+action	O
+of	O
+arachidonic	O
+acid	O
+,	O
+via	O
+a	O
+presumed	O
+cyclooxygenase	B-GENE
+product	O
+that	O
+mediated	O
+the	O
+contractions	O
+caused	O
+by	O
+both	O
+TF	B-GENE
+and	O
+EGF	B-GENE
+,	O
+was	O
+not	O
+blocked	O
+by	O
+any	O
+of	O
+the	O
+signal	O
+pathway	O
+probe	O
+inhibitors	O
+.	O
+
+On	O
+a	O
+separate	O
+occasion	O
+the	O
+T1	O
+weighted	O
+and	O
+T2	O
+weighted	O
+sagittal	O
+and	O
+T2	O
+weighted	O
+axial	O
+sequences	O
+were	O
+reported	O
+blind	O
+in	O
+relation	O
+to	O
+the	O
+initial	O
+assessment	O
+.	O
+
+The	O
+iron	O
+dependence	O
+of	O
+transcription	O
+and	O
+expression	O
+of	O
+cvaA	B-GENE
+,	O
+which	O
+encodes	O
+a	O
+transporter	O
+accessory	O
+protein	O
+,	O
+and	O
+cvi	B-GENE
+,	O
+encoding	O
+the	O
+colicin	B-GENE
+V	I-GENE
+immunity	I-GENE
+protein	I-GENE
+,	O
+was	O
+assessed	O
+under	O
+conditions	O
+of	O
+iron	O
+excess	O
+or	O
+depletion	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+deletion	O
+of	O
+bcp	B-GENE
+from	O
+the	O
+chromosome	O
+had	O
+no	O
+effect	O
+on	O
+gcv	B-GENE
+-	O
+lacZ	B-GENE
+expression	O
+.	O
+
+Of	O
+these	O
+sites	O
+,	O
+PEA3	B-GENE
+and	O
+STAT	B-GENE
+contributed	O
+specifically	O
+to	O
+induction	O
+by	O
+v	B-GENE
+-	I-GENE
+src	I-GENE
+,	O
+whereas	O
+the	O
+remaining	O
+elements	O
+were	O
+also	O
+involved	O
+in	O
+induction	O
+by	O
+the	O
+phorbol	O
+ester	O
+phorbol	O
+myristate	O
+acetate	O
+(	O
+PMA	O
+)	O
+.	O
+
+BRCA1	B-GENE
+protein	I-GENE
+contains	O
+an	O
+amino	O
+-	O
+terminal	O
+zinc	O
+finger	O
+motif	O
+and	O
+a	O
+carboxy	O
+-	O
+terminal	O
+acidic	O
+region	O
+.	O
+
+The	O
+mitochondrial	B-GENE
+regulatory	I-GENE
+region	I-GENE
+(	O
+mrr	B-GENE
+)	O
+located	O
+between	O
+the	O
+tRNAPhe	B-GENE
+and	O
+tRNAPro	B-GENE
+genes	I-GENE
+of	O
+mitochondrial	O
+DNA	O
+(	O
+mtDNA	O
+)	O
+is	O
+essential	O
+for	O
+regulation	O
+of	O
+replication	O
+and	O
+transcription	O
+of	O
+the	O
+mitochondrial	O
+genome	O
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+investigate	O
+the	O
+mechanism	O
+underlying	O
+Ras	B-GENE
+activation	O
+upon	O
+stimulation	O
+of	O
+these	O
+two	O
+types	O
+of	O
+receptors	O
+in	O
+hematopoietic	O
+cells	O
+.	O
+
+Thus	O
+,	O
+Sir	B-GENE
+proteins	I-GENE
+from	O
+K	O
+.	O
+lactis	O
+have	O
+roles	O
+in	O
+both	O
+silencing	O
+and	O
+telomere	O
+length	O
+maintenance	O
+,	O
+reflecting	O
+conserved	O
+functional	O
+themes	O
+.	O
+
+These	O
+mutants	O
+were	O
+tested	O
+for	O
+ability	O
+to	O
+bind	O
+each	O
+of	O
+the	O
+Site	B-GENE
+II	I-GENE
+cognate	I-GENE
+proteins	I-GENE
+,	O
+and	O
+subsequently	O
+evaluated	O
+for	O
+ability	O
+to	O
+confer	O
+H4	B-GENE
+transcriptional	O
+activity	O
+using	O
+chimeric	O
+H4	B-GENE
+promoter	O
+/	O
+CAT	B-GENE
+fusion	O
+constructs	O
+in	O
+different	O
+cell	O
+types	O
+.	O
+
+Increased	O
+plasma	O
+IgE	B-GENE
+was	O
+also	O
+confirmed	O
+in	O
+the	O
+NC	O
+mice	O
+,	O
+and	O
+treatment	O
+with	O
+FK506	O
+ointment	O
+reduced	O
+the	O
+plasma	O
+IgE	B-GENE
+level	O
+.	O
+
+Furthermore	O
+,	O
+in	O
+the	O
+ischemia	O
+/	O
+angiotension	B-GENE
+II	I-GENE
+-	O
+induced	O
+AHF	O
+model	O
+,	O
+NIC	O
+decreased	O
+left	O
+ventricular	O
+end	O
+-	O
+diastolic	O
+pressure	O
+(	O
+LVEDP	O
+)	O
+.	O
+
+Group	O
+A	O
+(	O
+68	O
+.	O
+7	O
++	O
+/	O
+-	O
+2	O
+.	O
+7	O
+years	O
+)	O
+consisted	O
+of	O
+patients	O
+with	O
+0	O
+or	O
+1	O
+risk	O
+factors	O
+;	O
+B	O
+(	O
+68	O
+.	O
+3	O
++	O
+/	O
+-	O
+4	O
+.	O
+2	O
+years	O
+)	O
+those	O
+with	O
+2	O
+risk	O
+factors	O
+;	O
+and	O
+C	O
+(	O
+69	O
+.	O
+2	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+years	O
+)	O
+those	O
+with	O
+3	O
+or	O
+more	O
+risk	O
+factors	O
+.	O
+
+We	O
+further	O
+demonstrate	O
+that	O
+RU486	O
+-	O
+PR	B-GENE
+-	I-GENE
+B	I-GENE
+interacts	O
+physically	O
+with	O
+NCoR	B-GENE
+in	O
+vitro	O
+.	O
+
+PRL	B-GENE
+receptor	I-GENE
+also	O
+activates	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+a	O
+cytosolic	B-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+.	O
+
+The	O
+dominant	O
+negative	O
+mutant	O
+of	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+was	O
+found	O
+to	O
+inhibit	O
+the	O
+induction	O
+of	O
+tyrosine	O
+phosphorylation	O
+and	O
+DNA	O
+-	O
+binding	O
+activity	O
+of	O
+m	B-GENE
+-	I-GENE
+Stat5a	I-GENE
+,	O
+m	B-GENE
+-	I-GENE
+Stat5b	I-GENE
+,	O
+and	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+deletion	O
+variant	O
+m	B-GENE
+-	I-GENE
+Stat5adelta749	I-GENE
+,	O
+as	O
+well	O
+as	O
+the	O
+transactivation	O
+potential	O
+of	O
+m	B-GENE
+-	I-GENE
+Stat5a	I-GENE
+and	O
+m	B-GENE
+-	I-GENE
+Stat5b	I-GENE
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+routinely	O
+collected	O
+data	O
+provided	O
+quantitative	O
+estimates	O
+of	O
+changes	O
+in	O
+CBZ	O
+Cl	O
+/	O
+F	O
+due	O
+to	O
+comedication	O
+and	O
+an	O
+age	O
+-	O
+related	O
+decrease	O
+in	O
+Cl	O
+/	O
+F	O
+The	O
+derived	O
+regression	O
+equations	O
+reasonably	O
+predicted	O
+concentrations	O
+in	O
+a	O
+separate	O
+validation	O
+set	O
+.	O
+
+Sites	O
+1	O
+and	O
+4	O
+in	O
+lumican	B-GENE
+and	O
+keratocan	B-GENE
+are	O
+in	O
+a	O
+homologous	O
+location	O
+.	O
+
+ATP	O
+-	O
+dependent	O
+assembly	O
+of	O
+a	O
+ternary	O
+complex	O
+consisting	O
+of	O
+a	O
+DNA	O
+mismatch	O
+and	O
+the	O
+yeast	O
+MSH2	B-GENE
+-	O
+MSH6	B-GENE
+and	O
+MLH1	B-GENE
+-	O
+PMS1	B-GENE
+protein	O
+complexes	O
+.	O
+
+Mutation	O
+of	O
+the	O
+central	O
+Tyr497	O
+to	O
+Phe	O
+blocks	O
+the	O
+tyrosine	O
+phosphorylation	O
+of	O
+the	O
+insulin	B-GENE
+receptor	I-GENE
+substrate	I-GENE
+1	I-GENE
+(	O
+IRS1	B-GENE
+)	O
+and	O
+diminishes	O
+proliferation	O
+in	O
+response	O
+to	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+.	O
+
+Instead	O
+,	O
+it	O
+contained	O
+two	O
+tandem	O
+kappaB	B-GENE
+elements	I-GENE
+and	O
+a	O
+variant	O
+activating	B-GENE
+transcription	I-GENE
+factor	I-GENE
+/	I-GENE
+cAMP	I-GENE
+response	I-GENE
+element	I-GENE
+site	O
+,	O
+which	O
+closely	O
+resembled	O
+sites	O
+in	O
+the	O
+E	B-GENE
+-	I-GENE
+selectin	I-GENE
+gene	I-GENE
+that	O
+are	O
+required	O
+for	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+-	O
+or	O
+LPS	O
+-	O
+inducible	O
+expression	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+activated	O
+PDGF	B-GENE
+beta	I-GENE
+-	I-GENE
+receptor	I-GENE
+was	O
+found	O
+not	O
+to	O
+bind	O
+Crk	B-GENE
+proteins	I-GENE
+.	O
+
+Furthermore	O
+,	O
+interactions	O
+were	O
+identified	O
+between	O
+endogenous	B-GENE
+E	I-GENE
+-	I-GENE
+cadherin	I-GENE
+and	O
+the	O
+chimera	O
+containing	O
+the	O
+E	B-GENE
+-	I-GENE
+cadherin	I-GENE
+extracellular	I-GENE
+domain	I-GENE
+and	O
+the	O
+desmoglein	B-GENE
+1	I-GENE
+intracellular	I-GENE
+domain	I-GENE
+providing	O
+in	O
+vivo	O
+evidence	O
+for	O
+previously	O
+predicted	O
+lateral	O
+interactions	O
+of	O
+E	B-GENE
+-	I-GENE
+cadherin	I-GENE
+extracellular	I-GENE
+domains	I-GENE
+.	O
+
+The	O
+ether	O
+phospholipid	O
+1	O
+-	O
+O	O
+-	O
+octadecyl	O
+-	O
+2	O
+-	O
+O	O
+-	O
+methyl	O
+-	O
+rac	O
+-	O
+glycero	O
+-	O
+3	O
+-	O
+phosphocholine	O
+(	O
+ET	O
+-	O
+18	O
+-	O
+OCH3	O
+;	O
+edelfosine	O
+)	O
+is	O
+a	O
+potent	O
+inducer	O
+of	O
+apoptosis	O
+in	O
+human	O
+tumor	O
+cells	O
+.	O
+
+In	O
+addition	O
+to	O
+a	O
+previously	O
+characterized	O
+promoter	O
+(	O
+P1	O
+)	O
+,	O
+we	O
+now	O
+show	O
+the	O
+existence	O
+of	O
+a	O
+second	O
+promoter	O
+for	O
+the	O
+human	B-GENE
+IL	I-GENE
+-	I-GENE
+5Ralpha	I-GENE
+gene	I-GENE
+.	O
+
+Serum	O
+levels	O
+of	O
+testosterone	O
+also	O
+showed	O
+no	O
+significant	O
+changes	O
+by	O
+exposure	O
+to	O
+p	O
+,	O
+p	O
+'	O
+-	O
+DDE	O
+under	O
+the	O
+conditions	O
+of	O
+this	O
+study	O
+.	O
+
+Overall	O
+agreement	O
+between	O
+rest	O
+/	O
+postnitroglycerin	O
+technetium	O
+-	O
+99m	O
+tetrofosmin	O
+SPET	O
+studies	O
+and	O
+rest	O
+/	O
+redistribution	O
+or	O
+rest	O
+/	O
+reinjection	O
+thallium	O
+-	O
+201	O
+SPET	O
+studies	O
+,	O
+regarding	O
+the	O
+presence	O
+of	O
+myocardial	O
+viability	O
+,	O
+was	O
+87	O
+%	O
+and	O
+90	O
+%	O
+,	O
+respectively	O
+.	O
+
+Their	O
+use	O
+resulted	O
+in	O
+a	O
+sensitivity	O
+of	O
+73	O
+%	O
+and	O
+a	O
+specificity	O
+of	O
+74	O
+%	O
+with	O
+regard	O
+to	O
+predictability	O
+of	O
+ALT	B-GENE
+levels	O
+increasing	O
+during	O
+the	O
+trial	O
+.	O
+
+One	O
+hundred	O
+replicate	O
+data	O
+sets	O
+of	O
+100	O
+subjects	O
+each	O
+were	O
+simulated	O
+for	O
+each	O
+missing	O
+data	O
+scenario	O
+.	O
+
+Spatial	O
+accuracy	O
+of	O
+primary	O
+and	O
+secondary	O
+memory	O
+-	O
+guided	O
+saccades	O
+in	O
+schizophrenic	O
+patients	O
+.	O
+
+Successful	O
+treatment	O
+with	O
+nasal	O
+continuous	O
+positive	O
+airway	O
+pressure	O
+(	O
+8	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+5	O
+cmH2O	O
+)	O
+for	O
+3	O
+days	O
+caused	O
+a	O
+significant	O
+decrease	O
+in	O
+mean	O
+blood	O
+pressure	O
+in	O
+OSAS	O
+.	O
+
+When	O
+data	O
+were	O
+expressed	O
+in	O
+a	O
+cumulative	O
+manner	O
+,	O
+the	O
+response	O
+to	O
+intravenous	O
+adenosine	O
+3	O
+mg	O
+,	O
+6	O
+mg	O
+,	O
+9	O
+mg	O
+and	O
+12	O
+mg	O
+in	O
+the	O
+24	O
+episodes	O
+of	O
+PSVT	O
+were	O
+5	O
+episodes	O
+(	O
+21	O
+%	O
+)	O
+,	O
+16	O
+episodes	O
+(	O
+67	O
+%	O
+)	O
+,	O
+20	O
+episodes	O
+(	O
+83	O
+%	O
+)	O
+and	O
+20	O
+episodes	O
+(	O
+83	O
+%	O
+)	O
+respectively	O
+.	O
+
+RNAs	O
+are	O
+not	O
+only	O
+essential	O
+components	O
+of	O
+both	O
+ribosomal	O
+subunits	O
+but	O
+also	O
+transiently	O
+interacting	O
+factors	O
+during	O
+particle	O
+formation	O
+.	O
+
+To	O
+study	O
+retinoid	O
+signalling	O
+in	O
+zebrafish	O
+embryos	O
+,	O
+we	O
+developed	O
+a	O
+novel	O
+method	O
+to	O
+detect	O
+endogenous	O
+retinoids	O
+in	O
+situ	O
+in	O
+embryos	O
+,	O
+using	O
+a	O
+fusion	O
+protein	O
+of	O
+the	O
+ligand	O
+inducible	O
+transactivation	O
+domain	O
+of	O
+a	O
+retinoic	B-GENE
+acid	I-GENE
+receptor	I-GENE
+and	O
+a	O
+heterologous	O
+DNA	O
+binding	O
+domain	O
+.	O
+
+Fluorescence	O
+in	O
+situ	O
+hybridization	O
+of	O
+metaphase	O
+spreads	O
+of	O
+chromosome	O
+8	O
+,	O
+containing	O
+hybrid	O
+cell	O
+line	O
+706	O
+-	O
+B6	O
+clone	O
+17	O
+(	O
+CL	O
+-	O
+17	O
+)	O
+with	O
+cosmid	O
+c101F1	O
+,	O
+placed	O
+the	O
+9804	B-GENE
+gene	I-GENE
+close	O
+to	O
+the	O
+telomere	O
+at	O
+8q24	O
+.	O
+3	O
+.	O
+
+Cell	O
+survival	O
+by	O
+Epo	B-GENE
+did	O
+not	O
+require	O
+activation	O
+of	O
+other	O
+known	O
+signaling	O
+pathways	O
+including	O
+PI	B-GENE
+-	I-GENE
+3	I-GENE
+kinase	I-GENE
+,	O
+PLC	B-GENE
+-	I-GENE
+gamma	I-GENE
+,	O
+Ras	B-GENE
+or	O
+Stats	B-GENE
+.	O
+
+The	O
+N	O
+-	O
+syndecan	O
+-	O
+dependent	O
+neurite	O
+outgrowth	O
+is	O
+inhibited	O
+by	O
+the	O
+tyrosine	B-GENE
+kinase	I-GENE
+inhibitors	O
+herbimycin	O
+A	O
+and	O
+PP1	B-GENE
+.	O
+
+An	O
+in	O
+vivo	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+substrate	O
+,	O
+SLP	B-GENE
+-	I-GENE
+76	I-GENE
+,	O
+implicated	O
+in	O
+Erk	B-GENE
+activation	O
+,	O
+also	O
+became	O
+rapidly	O
+tyrosine	O
+-	O
+phosphorylated	O
+in	O
+Jurkat	O
+cells	O
+,	O
+but	O
+not	O
+in	O
+P116	O
+cells	O
+,	O
+upon	O
+treatment	O
+with	O
+H2O2	O
+.	O
+
+The	O
+pharmacokinetic	O
+patterns	O
+of	O
+estradiol	O
+(	O
+CAS	O
+50	O
+-	O
+28	O
+-	O
+2	O
+)	O
+and	O
+of	O
+estrone	O
+(	O
+CAS	O
+53	O
+-	O
+16	O
+-	O
+7	O
+)	O
+were	O
+investigated	O
+in	O
+18	O
+women	O
+in	O
+natural	O
+or	O
+surgical	O
+menopause	O
+during	O
+the	O
+application	O
+of	O
+a	O
+new	O
+estradiol	O
+transdermal	O
+patch	O
+with	O
+active	O
+matrix	O
+and	O
+without	O
+absorption	O
+enhancers	O
+designed	O
+for	O
+epicutaneous	O
+applications	O
+of	O
+7	O
+days	O
+(	O
+hereinafter	O
+called	O
+"	O
+patch	O
+7D	O
+"	O
+)	O
+.	O
+
+Conversely	O
+,	O
+the	O
+central	O
+regions	O
+are	O
+highly	O
+variable	O
+.	O
+
+Among	O
+the	O
+H	B-GENE
+/	I-GENE
+ACA	I-GENE
+snoRNAs	I-GENE
+associated	O
+with	O
+Gar1p	B-GENE
+,	O
+one	O
+can	O
+distinguish	O
+a	O
+large	O
+group	O
+of	O
+snoRNAs	O
+that	O
+are	O
+not	O
+essential	O
+in	O
+yeast	O
+and	O
+serve	O
+as	O
+guides	O
+for	O
+pseudouridine	O
+synthesis	O
+onto	O
+the	O
+pre	O
+-	O
+rRNA	O
+molecule	O
+.	O
+
+Further	O
+studies	O
+demonstrated	O
+that	O
+the	O
+PPARalpha	B-GENE
+ligand	O
+8	O
+(	O
+S	O
+)	O
+-	O
+hydroxyeicosatetraenoic	O
+acid	O
+strongly	O
+promotes	O
+the	O
+interaction	O
+of	O
+PPARalpha	B-GENE
+with	O
+the	O
+co	O
+-	O
+activator	O
+RIP	B-GENE
+-	I-GENE
+140	I-GENE
+but	O
+decreases	O
+the	O
+interaction	O
+of	O
+PPARalpha	B-GENE
+with	O
+the	O
+co	O
+-	O
+repressor	O
+SMRT	B-GENE
+.	O
+
+We	O
+previously	O
+demonstrated	O
+that	O
+acute	O
+expression	O
+of	O
+the	O
+bovine	O
+papillomavirus	O
+type	O
+1	O
+(	O
+BPV1	O
+)	O
+E2	B-GENE
+protein	I-GENE
+in	O
+HeLa	O
+and	O
+HT	O
+-	O
+3	O
+cervical	O
+carcinoma	O
+cell	O
+lines	O
+greatly	O
+reduced	O
+cellular	O
+proliferation	O
+by	O
+imposing	O
+a	O
+specific	O
+G1	O
+/	O
+S	O
+phase	O
+growth	O
+arrest	O
+.	O
+
+Four	O
+possible	O
+isoforms	O
+(	O
+hGli2	B-GENE
+alpha	I-GENE
+,	I-GENE
+beta	I-GENE
+,	I-GENE
+gamma	I-GENE
+,	I-GENE
+and	I-GENE
+delta	I-GENE
+)	O
+are	O
+formed	O
+by	O
+combinations	O
+of	O
+two	O
+independent	O
+alternative	O
+splicings	O
+,	O
+and	O
+all	O
+the	O
+isoforms	O
+could	O
+bind	O
+to	O
+a	O
+DNA	O
+motif	O
+,	O
+TRE2S	O
+,	O
+in	O
+the	O
+LTR	O
+.	O
+
+Specialized	O
+actin	B-GENE
+tails	O
+that	O
+propel	O
+IEV	O
+particles	O
+to	O
+the	O
+periphery	O
+and	O
+virus	O
+-	O
+tipped	O
+microvilli	O
+(	O
+both	O
+common	O
+in	O
+wild	O
+-	O
+type	O
+-	O
+infected	O
+cells	O
+)	O
+were	O
+absent	O
+in	O
+cells	O
+infected	O
+with	O
+vA33delta	O
+.	O
+
+Their	O
+mean	O
+IOP	O
+was	O
+15	O
+.	O
+3	O
+(	O
+SD	O
+3	O
+.	O
+7	O
+)	O
+mmHg	O
+prior	O
+to	O
+induction	O
+of	O
+anesthesia	O
+,	O
+13	O
+.	O
+5	O
+(	O
+SD	O
+3	O
+.	O
+5	O
+)	O
+mmHg	O
+after	O
+loss	O
+of	O
+eyelash	O
+reflex	O
+following	O
+injection	O
+of	O
+methohexitone	O
+,	O
+16	O
+.	O
+1	O
+(	O
+SD	O
+2	O
+.	O
+4	O
+)	O
+mmHg	O
+after	O
+cessation	O
+of	O
+muscle	O
+fasciculations	O
+induced	O
+by	O
+suxamethonium	O
+,	O
+19	O
+.	O
+2	O
+(	O
+SD	O
+5	O
+.	O
+6	O
+)	O
+mmHg	O
+after	O
+cessation	O
+of	O
+convulsion	O
+and	O
+15	O
+.	O
+5	O
+(	O
+SD	O
+4	O
+.	O
+4	O
+)	O
+mmHg	O
+following	O
+resumption	O
+of	O
+regular	O
+spontaneous	O
+respiration	O
+.	O
+
+A	O
+cDNA	O
+,	O
+cak1At	B-GENE
+,	O
+was	O
+isolated	O
+that	O
+suppressed	O
+the	O
+CAK	B-GENE
+mutation	I-GENE
+in	O
+budding	O
+yeast	O
+,	O
+and	O
+it	O
+also	O
+complemented	O
+a	O
+fission	B-GENE
+yeast	I-GENE
+CAK	I-GENE
+mutant	I-GENE
+.	O
+cak1At	B-GENE
+encodes	O
+a	O
+protein	O
+related	O
+to	O
+animal	B-GENE
+CAKs	I-GENE
+.	O
+
+Post	O
+-	O
+translational	O
+modifications	O
+such	O
+as	O
+glycosylation	O
+and	O
+phosphorylation	O
+could	O
+be	O
+excluded	O
+as	O
+potential	O
+explanations	O
+for	O
+the	O
+protein	O
+heterogeneity	O
+.	O
+
+In	O
+addition	O
+to	O
+restoring	O
+checkpoint	O
+control	O
+,	O
+overexpression	O
+of	O
+sum1	B-GENE
++	I-GENE
+inhibits	O
+the	O
+normal	O
+cell	O
+cycle	O
+response	O
+to	O
+osmotic	O
+stress	O
+.	O
+
+Ime1	B-GENE
+plays	O
+a	O
+pivotal	O
+role	O
+in	O
+the	O
+initiation	O
+of	O
+meiosis	O
+in	O
+a	O
+/	O
+alpha	O
+diploid	O
+cells	O
+of	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+Rhesus	O
+macaques	O
+and	O
+BALB	O
+/	O
+c	O
+mice	O
+inoculated	O
+with	O
+the	O
+Mengo	O
+virus	O
+SIV	O
+recombinants	O
+failed	O
+to	O
+develop	O
+CTL	O
+responses	O
+against	O
+the	O
+SIV	O
+gene	O
+products	O
+,	O
+while	O
+one	O
+of	O
+the	O
+HIV	B-GENE
+-	I-GENE
+Nef	I-GENE
+recombinants	I-GENE
+induced	O
+a	O
+weak	O
+CTL	O
+response	O
+in	O
+mice	O
+directed	O
+to	O
+an	O
+HIV1	B-GENE
+Nef	I-GENE
+peptide	I-GENE
+spanning	O
+positions	O
+182	O
+-	O
+198	O
+.	O
+
+Deltamethrin	O
+was	O
+most	O
+effective	O
+on	O
+the	O
+thatched	O
+surface	O
+and	O
+produced	O
+100	O
+%	O
+mortality	O
+of	O
+An	O
+.	O
+culicifacies	O
+adults	O
+up	O
+to	O
+12	O
+weeks	O
+,	O
+even	O
+when	O
+exposed	O
+at	O
+the	O
+lowest	O
+dose	O
+/	O
+12	O
+.	O
+5	O
+mg	O
+/	O
+m2	O
+.	O
+
+Trichloroethylene	O
+,	O
+in	O
+turn	O
+,	O
+increased	O
+the	O
+AUC	O
+5	O
+.	O
+0	O
+(	O
+1	O
+.	O
+9	O
+-	O
+13	O
+.	O
+4	O
+)	O
+,	O
+25	O
+.	O
+8	O
+(	O
+8	O
+.	O
+2	O
+-	O
+80	O
+.	O
+8	O
+)	O
+and	O
+2	O
+.	O
+9	O
+(	O
+1	O
+.	O
+6	O
+-	O
+5	O
+.	O
+4	O
+)	O
+,	O
+respectively	O
+,	O
+whereas	O
+the	O
+corresponding	O
+values	O
+for	O
+n	O
+-	O
+hexane	O
+were	O
+1	O
+.	O
+9	O
+(	O
+0	O
+.	O
+7	O
+-	O
+5	O
+.	O
+1	O
+)	O
+,	O
+1	O
+.	O
+5	O
+(	O
+0	O
+.	O
+5	O
+-	O
+4	O
+.	O
+6	O
+)	O
+,	O
+and	O
+3	O
+.	O
+2	O
+(	O
+1	O
+.	O
+8	O
+-	O
+5	O
+.	O
+9	O
+)	O
+.	O
+
+Solution	O
+structure	O
+of	O
+the	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+domain	I-GENE
+:	O
+a	O
+novel	O
+subgroup	O
+of	O
+the	O
+winged	B-GENE
+helix	I-GENE
+-	I-GENE
+turn	I-GENE
+-	I-GENE
+helix	I-GENE
+family	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+receptor	B-GENE
+/	I-GENE
+G	I-GENE
+protein	I-GENE
+coupling	O
+appeared	O
+unaffected	O
+by	O
+expression	O
+of	O
+loop	O
+3i	O
+domains	O
+derived	O
+from	O
+two	O
+receptors	O
+coupled	O
+to	O
+G	B-GENE
+(	I-GENE
+i	I-GENE
+/	I-GENE
+o	I-GENE
+)	I-GENE
+proteins	I-GENE
+(	O
+M2Ach	B-GENE
+-	I-GENE
+muscarinic	I-GENE
+and	I-GENE
+alpha2A	I-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptors	I-GENE
+)	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+third	O
+intracellular	O
+loop	O
+of	O
+the	O
+rat	B-GENE
+GnRH	I-GENE
+-	I-GENE
+R	I-GENE
+is	O
+involved	O
+in	O
+receptor	B-GENE
+G	I-GENE
+(	I-GENE
+q	I-GENE
+/	I-GENE
+11	I-GENE
+)	I-GENE
+protein	I-GENE
+coupling	O
+and	O
+/	O
+or	O
+selectivity	O
+,	O
+and	O
+in	O
+the	O
+GGH	O
+(	O
+3	O
+)	O
+1	O
+'	O
+cell	O
+line	O
+,	O
+this	O
+loop	O
+is	O
+also	O
+involved	O
+in	O
+signal	O
+transduction	O
+mediated	O
+through	O
+the	O
+Gs	B-GENE
+protein	O
+pathway	O
+.	O
+
+Decreased	O
+levels	O
+of	O
+alpha2	B-GENE
+-	I-GENE
+antiplasmin	I-GENE
+were	O
+also	O
+observed	O
+in	O
+the	O
+mediastinum	O
+(	O
+0	O
+.	O
+50	O
+versus	O
+0	O
+.	O
+61	O
+U	O
+/	O
+mL	O
+;	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+A	O
+catalytic	O
+domain	O
+of	O
+eukaryotic	B-GENE
+DNA	I-GENE
+topoisomerase	I-GENE
+I	I-GENE
+.	O
+
+A	O
+cluster	O
+of	O
+basic	O
+amino	O
+acids	O
+,	O
+KKKR	O
+,	O
+generated	O
+by	O
+joining	O
+of	O
+the	O
+sequences	O
+encoded	O
+by	O
+the	O
+constitutive	O
+exon	O
+13	O
+and	O
+the	O
+alternative	O
+exon	O
+16	O
+,	O
+is	O
+necessary	O
+for	O
+the	O
+nuclear	O
+targeting	O
+of	O
+4	B-GENE
+.	I-GENE
+1H	I-GENE
+,	O
+as	O
+demonstrated	O
+by	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+analysis	O
+.	O
+
+All	O
+three	O
+genes	O
+have	O
+been	O
+mapped	O
+precisely	O
+to	O
+a	O
+small	O
+region	O
+on	O
+human	O
+chromosome	O
+16p12	O
+.	O
+1	O
+-	O
+p11	O
+.	O
+2	O
+(	O
+homologous	O
+to	O
+mouse	O
+chromosome	O
+7	O
+)	O
+,	O
+using	O
+somatic	O
+cell	O
+hybrids	O
+and	O
+cosmid	O
+clones	O
+.	O
+
+In	O
+fus3	B-GENE
+mutants	I-GENE
+,	O
+the	O
+levels	O
+of	O
+Ty1	B-GENE
+RNA	I-GENE
+,	O
+protein	O
+synthesis	O
+,	O
+and	O
+proteolytic	O
+processing	O
+were	O
+not	O
+altered	O
+relative	O
+to	O
+those	O
+in	O
+FUS3	B-GENE
+strains	O
+but	O
+steady	O
+-	O
+state	O
+levels	O
+of	O
+TyA	B-GENE
+,	O
+integrase	B-GENE
+,	O
+and	O
+reverse	B-GENE
+transcriptase	I-GENE
+proteins	O
+and	O
+Ty1	B-GENE
+cDNA	I-GENE
+were	O
+all	O
+increased	O
+.	O
+
+Posttranslational	O
+regulation	O
+of	O
+Ty1	B-GENE
+retrotransposition	O
+by	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+Fus3	I-GENE
+.	O
+
+Their	O
+function	O
+is	O
+not	O
+only	O
+to	O
+recruit	O
+Pho2	B-GENE
+to	O
+the	O
+promoter	O
+but	O
+to	O
+allow	O
+cooperative	O
+binding	O
+of	O
+Pho4	B-GENE
+together	O
+with	O
+Pho2	B-GENE
+.	O
+
+Substitution	O
+of	O
+the	O
+Ser	O
+-	O
+Thr	O
+sites	O
+with	O
+the	O
+phosphomimetic	O
+Asp	O
+generated	O
+a	O
+constitutively	O
+active	O
+form	O
+of	O
+IRF	B-GENE
+-	I-GENE
+3	I-GENE
+that	O
+functioned	O
+as	O
+a	O
+very	O
+strong	O
+activator	O
+of	O
+promoters	O
+containing	O
+PRDI	B-GENE
+-	O
+PRDIII	B-GENE
+or	O
+ISRE	B-GENE
+regulatory	I-GENE
+elements	I-GENE
+.	O
+
+New	O
+-	O
+onset	O
+angina	O
+preceding	O
+acute	O
+myocardial	O
+infarction	O
+is	O
+associated	O
+with	O
+improved	O
+contractile	O
+recovery	O
+after	O
+thrombolysis	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+effect	O
+of	O
+acute	O
+administration	O
+of	O
+various	O
+doses	O
+of	O
+malathion	O
+via	O
+oral	O
+and	O
+dermal	O
+routes	O
+to	O
+mice	O
+and	O
+rats	O
+on	O
+serum	O
+levels	O
+of	O
+histamine	O
+was	O
+evaluated	O
+.	O
+
+Fetal	O
+growth	O
+retardation	O
+as	O
+a	O
+cause	O
+of	O
+impaired	O
+ovarian	O
+development	O
+.	O
+
+Similarly	O
+,	O
+PCDFs	O
+/	O
+PCDDs	O
+ratio	O
+in	O
+ESP	O
+ash	O
+was	O
+lower	O
+than	O
+that	O
+in	O
+boiler	O
+ash	O
+.	O
+
+In	O
+addition	O
+to	O
+DNA	O
+-	O
+protein	O
+interactions	O
+,	O
+protein	O
+-	O
+protein	O
+interactions	O
+with	O
+partner	O
+proteins	O
+often	O
+play	O
+major	O
+roles	O
+in	O
+targeting	O
+ETS	B-GENE
+-	I-GENE
+domain	I-GENE
+proteins	I-GENE
+to	O
+specific	O
+promoters	O
+.	O
+
+The	O
+complete	O
+exon	O
+-	O
+intron	O
+organization	O
+of	O
+the	O
+murine	O
+gene	O
+encoding	O
+M	B-GENE
+-	I-GENE
+protein	I-GENE
+,	O
+a	O
+structural	O
+protein	O
+of	O
+sarcomeric	O
+myofibrils	O
+,	O
+was	O
+determined	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+introduce	O
+an	O
+image	O
+analysis	O
+of	O
+the	O
+cornea	O
+in	O
+photorefractive	O
+keratectomy	O
+(	O
+PRK	O
+)	O
+for	O
+preoperative	O
+and	O
+early	O
+postoperative	O
+determination	O
+of	O
+changes	O
+in	O
+the	O
+condition	O
+of	O
+the	O
+cornea	O
+.	O
+
+Mean	O
++	O
+/	O
+-	O
+SD	O
+serum	B-GENE
+VEGF	I-GENE
+concentrations	O
+were	O
+significantly	O
+higher	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+women	O
+with	O
+PCO	O
+and	O
+PCOS	O
+(	O
+3	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+and	O
+3	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+66	O
+ng	O
+/	O
+ml	O
+respectively	O
+)	O
+compared	O
+with	O
+women	O
+with	O
+normal	O
+ovaries	O
+(	O
+2	O
+.	O
+3	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+ng	O
+/	O
+ml	O
+)	O
+.	O
+
+Strikingly	O
+,	O
+these	O
+cells	O
+contain	O
+a	O
+missense	O
+mutation	O
+of	O
+the	O
+p53	B-GENE
+gene	I-GENE
+at	O
+codon	O
+242	O
+(	O
+p53	B-GENE
+(	O
+242	O
+)	O
+)	O
+,	O
+which	O
+substitutes	O
+alanine	O
+for	O
+glycine	O
+.	O
+
+The	O
+new	O
+algorithm	O
+,	O
+called	O
+RBI	O
+-	O
+MAP	O
+,	O
+is	O
+based	O
+on	O
+the	O
+rescaled	O
+block	O
+iterative	O
+EM	O
+(	O
+RBI	O
+-	O
+EM	O
+)	O
+algorithm	O
+.	O
+
+A	O
+third	O
+ORF	O
+,	O
+ORF5	O
+,	O
+shows	O
+homology	O
+with	O
+gene	B-GENE
+agrB	I-GENE
+from	O
+Staphylococcus	O
+aureus	O
+,	O
+which	O
+is	O
+involved	O
+in	O
+the	O
+mechanism	O
+of	O
+regulation	O
+of	O
+the	O
+virulence	O
+phenotype	O
+in	O
+this	O
+species	O
+.	O
+
+An	O
+association	O
+between	O
+hSIE	B-GENE
+and	O
+Stat	B-GENE
+-	I-GENE
+3	I-GENE
+after	O
+MHC	B-GENE
+-	I-GENE
+I	I-GENE
+ligation	O
+was	O
+directly	O
+demonstrated	O
+by	O
+precipitating	O
+Stat	B-GENE
+-	I-GENE
+3	I-GENE
+from	O
+nuclear	O
+extracts	O
+with	O
+biotinylated	O
+hSIE	B-GENE
+probe	O
+and	O
+avidin	B-GENE
+-	O
+coupled	O
+agarose	O
+.	O
+
+Transcriptional	O
+repression	O
+mediated	O
+by	O
+LysR	B-GENE
+-	I-GENE
+type	I-GENE
+regulator	I-GENE
+CatR	I-GENE
+bound	O
+at	O
+multiple	O
+binding	O
+sites	O
+.	O
+
+Two	O
+of	O
+these	O
+resulted	O
+in	O
+increased	O
+levels	O
+of	O
+the	O
+alpha	O
+subunit	O
+,	O
+and	O
+one	O
+caused	O
+a	O
+substitution	O
+of	O
+glycine	O
+for	O
+the	O
+aspartic	O
+acid	O
+residue	O
+at	O
+position	O
+171	O
+,	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+domain	O
+.	O
+
+These	O
+two	O
+mRNA	O
+species	O
+are	O
+produced	O
+by	O
+differential	O
+polyadenylation	O
+site	O
+usage	O
+.	O
+
+Finally	O
+,	O
+a	O
+role	O
+for	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+in	O
+preventing	O
+apoptosis	O
+induced	O
+by	O
+ER	O
+calcium	O
+release	O
+was	O
+demonstrated	O
+by	O
+data	O
+showing	O
+that	O
+sAPPalpha	B-GENE
+prevents	O
+thapsigargin	O
+-	O
+induced	O
+apoptosis	O
+,	O
+an	O
+effect	O
+blocked	O
+by	O
+kappaB	B-GENE
+decoy	O
+DNA	O
+.	O
+
+Many	O
+cytokine	O
+receptors	O
+employ	O
+Janus	B-GENE
+protein	I-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+(	O
+Jaks	B-GENE
+)	O
+and	O
+signal	B-GENE
+transducers	I-GENE
+and	I-GENE
+activators	I-GENE
+of	I-GENE
+transcription	I-GENE
+(	O
+Stats	B-GENE
+)	O
+for	O
+nuclear	O
+signaling	O
+.	O
+
+A	O
+site	O
+-	O
+directed	O
+R618K	O
+mutation	O
+in	O
+the	O
+Stat5	B-GENE
+SH2	B-GENE
+domain	I-GENE
+abolished	O
+the	O
+phosphorylation	O
+by	O
+Jak2	B-GENE
+,	O
+while	O
+deletion	O
+of	O
+the	O
+C	O
+terminus	O
+led	O
+to	O
+Stat5	B-GENE
+hyperphosphorylation	O
+.	O
+
+Specifically	O
+,	O
+recombination	O
+at	O
+HMR	B-GENE
+was	O
+used	O
+to	O
+produce	O
+rings	O
+that	O
+lacked	O
+the	O
+E	O
+and	O
+I	O
+silencers	O
+.	O
+
+In	O
+angiodysplasia	O
+,	O
+ectatic	O
+vessels	O
+in	O
+the	O
+mucosa	O
+appeared	O
+to	O
+contain	O
+less	O
+collagen	B-GENE
+type	I-GENE
+IV	I-GENE
+than	O
+similarly	O
+sized	O
+vessels	O
+in	O
+the	O
+submucosa	O
+,	O
+and	O
+perforating	O
+vessels	O
+appeared	O
+in	O
+many	O
+cases	O
+to	O
+lose	O
+staining	O
+at	O
+the	O
+level	O
+of	O
+the	O
+muscularis	O
+mucosae	O
+.	O
+
+We	O
+studied	O
+the	O
+human	O
+vestibulo	O
+-	O
+ocular	O
+reflex	O
+(	O
+VOR	O
+)	O
+in	O
+response	O
+to	O
+head	O
+'	O
+impulses	O
+'	O
+:	O
+brief	O
+,	O
+unpredictable	O
+,	O
+passive	O
+,	O
+high	O
+-	O
+acceleration	O
+(	O
+up	O
+to	O
+4000	O
+degrees	O
+/	O
+s2	O
+)	O
+,	O
+low	O
+-	O
+amplitude	O
+(	O
+20	O
+-	O
+30	O
+degrees	O
+)	O
+head	O
+rotations	O
+.	O
+
+To	O
+clarify	O
+whether	O
+seizure	O
+-	O
+offset	O
+patterns	O
+are	O
+reliable	O
+in	O
+predicting	O
+seizure	O
+outcome	O
+,	O
+we	O
+studied	O
+SEEG	O
+/	O
+ECoG	O
+in	O
+a	O
+similar	O
+group	O
+of	O
+patients	O
+with	O
+temporal	O
+lobe	O
+epilepsy	O
+(	O
+TLE	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+to	O
+characterize	O
+the	O
+gene	O
+for	O
+protein	B-GENE
+Z	I-GENE
+,	O
+its	O
+organization	O
+and	O
+structure	O
+were	O
+determined	O
+by	O
+a	O
+combination	O
+of	O
+PCR	O
+amplification	O
+of	O
+leukocyte	O
+DNA	O
+and	O
+isolation	O
+of	O
+phage	O
+clones	O
+from	O
+a	O
+human	O
+genomic	O
+library	O
+.	O
+
+These	O
+modifications	O
+may	O
+improve	O
+the	O
+interlaboratory	O
+reproducibility	O
+of	O
+CD34	B-GENE
+determinations	O
+due	O
+to	O
+the	O
+reduction	O
+in	O
+sample	O
+handling	O
+and	O
+calculation	O
+of	O
+results	O
+.	O
+
+The	O
+present	O
+results	O
+demonstrate	O
+that	O
+rats	O
+with	O
+relatively	O
+small	O
+remnants	O
+of	O
+one	O
+olfactory	O
+bulb	O
+can	O
+perform	O
+a	O
+variety	O
+of	O
+odor	O
+detection	O
+and	O
+discrimination	O
+tasks	O
+as	O
+well	O
+or	O
+nearly	O
+as	O
+well	O
+as	O
+controls	O
+.	O
+
+These	O
+patients	O
+failed	O
+to	O
+respond	O
+to	O
+intravenous	O
+cyclophosphamide	O
+and	O
+steroids	O
+and	O
+were	O
+then	O
+changed	O
+to	O
+receive	O
+oral	O
+cyclosporine	O
+A	O
+,	O
+at	O
+a	O
+dose	O
+of	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+.	O
+
+The	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+is	O
+78	O
+.	O
+0	O
+%	O
+identical	O
+to	O
+the	O
+cytoplasmic	B-GENE
+dynein	I-GENE
+heavy	I-GENE
+chain	I-GENE
+of	I-GENE
+Neurospora	I-GENE
+crassa	I-GENE
+,	O
+70	O
+.	O
+2	O
+%	O
+identical	O
+to	O
+that	O
+of	O
+Aspergillus	O
+nidulans	O
+and	O
+24	O
+.	O
+8	O
+%	O
+identical	O
+to	O
+that	O
+of	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+The	O
+DNA	O
+binding	O
+activities	O
+of	O
+the	O
+three	O
+repressor	O
+preparations	O
+were	O
+studied	O
+using	O
+fragments	O
+containing	O
+CIRs	O
+(	O
+CIR3	O
+-	O
+CIR6	O
+)	O
+from	O
+the	O
+essential	O
+early	O
+region	O
+as	O
+templates	O
+for	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+.	O
+
+Molecular	O
+modelling	O
+suggested	O
+that	O
+the	O
+tetramerization	O
+domain	O
+was	O
+a	O
+four	O
+-	O
+helix	O
+bundle	O
+,	O
+stabilized	O
+by	O
+interactions	O
+of	O
+seven	O
+conserved	O
+aromatic	O
+amino	O
+acids	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+sought	O
+to	O
+investigate	O
+whether	O
+constitutive	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activity	O
+in	O
+chronically	O
+HIV	O
+-	O
+1	O
+-	O
+infected	O
+promonocytic	O
+U937	O
+(	O
+U9	O
+-	O
+IIIB	O
+)	O
+and	O
+myeloblastic	O
+PLB	O
+-	O
+985	O
+(	O
+PLB	O
+-	O
+IIIB	O
+)	O
+cells	O
+affects	O
+apoptotic	O
+signaling	O
+.	O
+
+To	O
+explore	O
+the	O
+function	O
+of	O
+human	O
+SINA	B-GENE
+-	I-GENE
+homologous	I-GENE
+(	I-GENE
+Siah	I-GENE
+)	I-GENE
+proteins	I-GENE
+,	O
+expression	O
+plasmids	O
+encoding	O
+Siah	B-GENE
+-	I-GENE
+1A	I-GENE
+were	O
+transiently	O
+transfected	O
+into	O
+293	O
+epithelial	O
+cells	O
+and	O
+GM701	O
+fibroblast	O
+cells	O
+,	O
+resulting	O
+in	O
+growth	O
+arrest	O
+without	O
+induction	O
+of	O
+apoptosis	O
+.	O
+
+We	O
+have	O
+shown	O
+previously	O
+that	O
+GH3	O
+cells	O
+transfected	O
+with	O
+the	O
+rat	B-GENE
+GnRH	I-GENE
+receptor	I-GENE
+cDNA	I-GENE
+(	O
+GGH3	O
+-	O
+1	O
+'	O
+cells	O
+)	O
+support	O
+the	O
+expression	O
+of	O
+a	O
+cotransfected	O
+fusion	O
+gene	O
+composed	O
+of	O
+797	O
+base	O
+pairs	O
+of	O
+rat	B-GENE
+LHbeta	I-GENE
+gene	I-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+flanking	I-GENE
+sequence	I-GENE
+and	O
+the	O
+first	O
+5	O
+base	O
+pairs	O
+of	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+fused	O
+to	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+(	I-GENE
+-	I-GENE
+797	I-GENE
+/	I-GENE
++	I-GENE
+5LHbetaLUC	I-GENE
+)	I-GENE
+and	O
+respond	O
+to	O
+a	O
+GnRH	B-GENE
+agonist	O
+with	O
+a	O
+10	O
+-	O
+fold	O
+stimulation	O
+of	O
+activity	O
+.	O
+
+The	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+,	O
+from	O
+nucleotide	O
+-	O
+837	O
+to	O
+-	O
+336	O
+,	O
+contains	O
+TATA	O
+and	O
+inverted	O
+CAAT	O
+boxes	O
+as	O
+well	O
+as	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+SP1	B-GENE
+erythroid	O
+-	O
+specific	O
+cis	O
+-	O
+acting	O
+regulatory	O
+elements	O
+.	O
+
+We	O
+established	O
+the	O
+radiosensitive	O
+cell	O
+line	O
+SX9	O
+from	O
+mammary	O
+carcinoma	O
+cell	O
+line	O
+FM3A	O
+.	O
+
+Results	O
+showed	O
+that	O
+the	O
+mean	O
+bond	O
+strength	O
+of	O
+H	O
+.	O
+T	O
+.	O
+V	O
+.	O
+specimens	O
+ranged	O
+from	O
+9	O
+.	O
+6	O
+to	O
+13	O
+.	O
+12	O
+kg	O
+/	O
+cm2	O
+,	O
+while	O
+the	O
+mean	O
+bond	O
+strength	O
+of	O
+R	O
+.	O
+T	O
+.	O
+V	O
+.	O
+specimens	O
+ranged	O
+from	O
+0	O
+.	O
+36	O
+to	O
+1	O
+.	O
+75	O
+kg	O
+/	O
+cm2	O
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+measure	O
+coagulation	B-GENE
+factor	I-GENE
+VIII	I-GENE
+:	I-GENE
+coagulant	I-GENE
+(	O
+F	B-GENE
+.	I-GENE
+VIII	I-GENE
+:	I-GENE
+C	I-GENE
+)	O
+and	O
+C1	B-GENE
+-	I-GENE
+esterase	I-GENE
+inhibitor	I-GENE
+(	O
+C1	B-GENE
+-	I-GENE
+INH	I-GENE
+)	O
+,	O
+hemostasis	O
+-	O
+associated	O
+acute	O
+-	O
+phase	O
+reactant	O
+proteins	O
+and	O
+coagulation	B-GENE
+factors	I-GENE
+VII	I-GENE
+(	O
+F	B-GENE
+.	I-GENE
+VII	I-GENE
+)	O
+,	O
+IX	O
+(	O
+F	B-GENE
+.	I-GENE
+IX	I-GENE
+)	O
+,	O
+and	O
+X	O
+(	O
+F	B-GENE
+.	I-GENE
+X	I-GENE
+)	O
+,	O
+hemostasis	O
+proteins	O
+not	O
+associated	O
+with	O
+an	O
+acute	O
+-	O
+phase	O
+response	O
+,	O
+in	O
+a	O
+select	O
+population	O
+of	O
+horses	O
+with	O
+colic	O
+and	O
+hemostasis	O
+abnormalities	O
+,	O
+and	O
+presumed	O
+to	O
+have	O
+acute	O
+-	O
+phase	O
+changes	O
+.	O
+
+RESULTS	O
+:	O
+Horses	O
+with	O
+colic	O
+had	O
+significantly	O
+higher	O
+fibrinogen	B-GENE
+concentration	O
+,	O
+greater	O
+alpha	B-GENE
+2AP	I-GENE
+and	O
+protein	B-GENE
+C	I-GENE
+activities	O
+,	O
+and	O
+longer	O
+PT	O
+and	O
+APTT	O
+than	O
+did	O
+healthy	O
+horses	O
+.	O
+
+The	O
+data	O
+suggest	O
+that	O
+plasminogen	B-GENE
+,	O
+alpha	B-GENE
+2AP	I-GENE
+,	O
+and	O
+C1	B-GENE
+-	I-GENE
+INH	I-GENE
+,	O
+should	O
+be	O
+considered	O
+equine	O
+acute	O
+-	O
+phase	O
+proteins	O
+.	O
+
+None	O
+of	O
+the	O
+patients	O
+was	O
+obese	O
+.	O
+
+Marked	O
+elevation	O
+of	O
+creatine	B-GENE
+kinase	I-GENE
+was	O
+observed	O
+while	O
+serum	O
+albumin	B-GENE
+,	O
+immunoglobulin	B-GENE
+,	O
+and	O
+complement	O
+were	O
+decreased	O
+.	O
+
+DESIGN	O
+AND	O
+METHODS	O
+:	O
+Case	O
+study	O
+.	O
+
+METHODS	O
+:	O
+A	O
+total	O
+of	O
+15	O
+pigs	O
+were	O
+randomised	O
+to	O
+ligation	O
+of	O
+left	O
+marginal	O
+arteries	O
+(	O
+infarction	O
+group	O
+,	O
+n	O
+=	O
+5	O
+)	O
+,	O
+to	O
+TMLR	O
+of	O
+the	O
+left	O
+lateral	O
+wall	O
+using	O
+a	O
+holmium	O
+:	O
+yttrium	O
+-	O
+aluminium	O
+garnet	O
+(	O
+Ho	O
+:	O
+YAG	O
+)	O
+laser	O
+(	O
+laser	O
+group	O
+,	O
+n	O
+=	O
+5	O
+)	O
+,	O
+and	O
+to	O
+both	O
+(	O
+laser	O
+-	O
+infarction	O
+group	O
+,	O
+n	O
+=	O
+5	O
+)	O
+.	O
+
+RACK1	B-GENE
+,	O
+a	O
+receptor	O
+for	O
+activated	B-GENE
+C	I-GENE
+kinase	I-GENE
+and	O
+a	O
+homolog	O
+of	O
+the	O
+beta	O
+subunit	O
+of	O
+G	B-GENE
+proteins	I-GENE
+,	O
+inhibits	O
+activity	O
+of	O
+src	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+and	O
+growth	O
+of	O
+NIH	O
+3T3	O
+cells	O
+.	O
+
+Peptide	O
+sequences	O
+of	O
+the	O
+zinc	B-GENE
+finger	I-GENE
+protein	I-GENE
+Ttk	I-GENE
+and	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+Adf	I-GENE
+-	I-GENE
+1	I-GENE
+were	O
+obtained	O
+.	O
+
+The	O
+same	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+-	O
+inducible	O
+reporter	O
+gene	O
+is	O
+also	O
+synergistically	O
+activated	O
+by	O
+the	O
+endogenous	B-GENE
+Stat6	I-GENE
+and	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+proteins	I-GENE
+in	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+-	O
+stimulated	O
+I	O
+.	O
+29mu	O
+B	O
+lymphoma	O
+cells	O
+.	O
+
+HEF1	B-GENE
+,	O
+p130	B-GENE
+(	O
+Cas	B-GENE
+)	O
+,	O
+and	O
+Efs	B-GENE
+/	O
+Sin	B-GENE
+constitute	O
+a	O
+family	O
+of	O
+multidomain	O
+docking	O
+proteins	O
+that	O
+have	O
+been	O
+implicated	O
+in	O
+coordinating	O
+the	O
+regulation	O
+of	O
+cell	O
+adhesion	O
+.	O
+
+In	O
+support	O
+of	O
+a	O
+role	O
+at	O
+the	O
+spindle	O
+,	O
+two	O
+-	O
+hybrid	O
+library	O
+screening	O
+with	O
+HEF1	B-GENE
+identifies	O
+the	O
+human	O
+homolog	O
+of	O
+the	O
+G2	B-GENE
+/	I-GENE
+M	I-GENE
+spindle	I-GENE
+-	I-GENE
+regulatory	I-GENE
+protein	I-GENE
+Dim1p	I-GENE
+as	O
+a	O
+specific	O
+interactor	O
+with	O
+a	O
+region	O
+of	O
+HEF1	B-GENE
+encompassed	O
+in	O
+p55	B-GENE
+(	O
+HEF1	B-GENE
+)	O
+.	O
+
+Our	O
+data	O
+showed	O
+that	O
+activation	O
+of	O
+the	O
+raf	B-GENE
+-	O
+ERK	B-GENE
+pathway	O
+led	O
+to	O
+activation	O
+of	O
+TF	B-GENE
+expression	O
+in	O
+breast	O
+carcinoma	O
+cells	O
+and	O
+suggested	O
+that	O
+constitutive	O
+activation	O
+of	O
+this	O
+pathway	O
+leads	O
+to	O
+high	O
+TF	B-GENE
+expression	O
+in	O
+MDA	O
+-	O
+MB	O
+-	O
+231	O
+cells	O
+.	O
+
+However	O
+,	O
+a	O
+zinc	O
+-	O
+depleted	O
+enzyme	O
+was	O
+obtained	O
+after	O
+prolonged	O
+dialysis	O
+against	O
+the	O
+specific	O
+chelating	O
+agent	O
+1	O
+,	O
+10	O
+-	O
+phenanthroline	O
+.	O
+
+The	O
+lines	O
+also	O
+differed	O
+in	O
+postsynaptic	O
+,	O
+but	O
+not	O
+presynaptic	O
+,	O
+5	B-GENE
+-	I-GENE
+HT1A	I-GENE
+receptors	I-GENE
+.	O
+
+Convulsive	O
+seizure	O
+during	O
+a	O
+treatment	O
+with	O
+interferon	B-GENE
+alpha	I-GENE
+for	O
+chronic	O
+viral	O
+hepatitis	O
+C	O
+
+Genetic	O
+studies	O
+in	O
+Drosophila	O
+have	O
+led	O
+to	O
+the	O
+identification	O
+of	O
+several	O
+components	O
+of	O
+the	O
+Notch	B-GENE
+pathway	O
+.	O
+
+The	O
+bZP2	B-GENE
+cDNA	I-GENE
+(	I-GENE
+115	I-GENE
+-	I-GENE
+1914	I-GENE
+nt	I-GENE
+,	I-GENE
+1	I-GENE
+.	I-GENE
+8	I-GENE
+kb	I-GENE
+)	I-GENE
+,	O
+excluding	O
+sequences	O
+coding	O
+for	O
+N	O
+-	O
+terminal	O
+signal	O
+sequence	O
+and	O
+C	O
+-	O
+terminal	O
+transmembranelike	O
+domain	O
+,	O
+was	O
+PCR	O
+amplified	O
+and	O
+Sac1	B-GENE
+-	O
+Sal1	B-GENE
+restricted	O
+fragment	O
+cloned	O
+in	O
+frame	O
+downstream	O
+of	O
+the	O
+T5	O
+promoter	O
+under	O
+the	O
+lac	B-GENE
+operator	I-GENE
+control	O
+in	O
+a	O
+pQE	O
+-	O
+30	O
+vector	O
+.	O
+
+Control	O
+subjects	O
+'	O
+evoked	O
+potentials	O
+(	O
+EPs	O
+)	O
+were	O
+characterized	O
+by	O
+an	O
+initial	O
+positivity	O
+in	O
+the	O
+90	O
+-	O
+140	O
+ms	O
+range	O
+(	O
+P1	O
+)	O
+at	O
+the	O
+temporo	O
+-	O
+occipital	O
+site	O
+.	O
+
+Class	B-GENE
+I	I-GENE
+alpha1	I-GENE
+,	I-GENE
+2	I-GENE
+-	I-GENE
+mannosidases	I-GENE
+play	O
+an	O
+essential	O
+role	O
+in	O
+the	O
+elaboration	O
+of	O
+complex	O
+and	O
+hybrid	O
+N	O
+-	O
+glycans	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Structural	O
+features	O
+of	O
+the	O
+minimal	O
+DNA	O
+binding	O
+domain	O
+(	O
+M98	O
+-	O
+F219	O
+)	O
+of	O
+human	B-GENE
+nucleotide	I-GENE
+excision	I-GENE
+repair	I-GENE
+protein	I-GENE
+XPA	I-GENE
+.	O
+
+Amongst	O
+other	O
+qualities	O
+,	O
+the	O
+book	O
+'	O
+s	O
+importance	O
+lies	O
+in	O
+the	O
+fact	O
+that	O
+it	O
+associates	O
+an	O
+elaborate	O
+theoretical	O
+construction	O
+with	O
+the	O
+empirical	O
+data	O
+,	O
+working	O
+within	O
+the	O
+possibilities	O
+provided	O
+by	O
+late	O
+19th	O
+-	O
+century	O
+moral	O
+statistics	O
+.	O
+
+The	O
+results	O
+point	O
+to	O
+the	O
+effectiveness	O
+of	O
+the	O
+educational	O
+intervention	O
+.	O
+
+The	O
+mechanistic	O
+implications	O
+of	O
+aromatic	O
+non	O
+-	O
+responsiveness	O
+of	O
+autonomously	O
+expressed	O
+A	O
+-	O
+domain	O
+,	O
+despite	O
+its	O
+demonstrated	O
+ability	O
+to	O
+bind	O
+phenol	O
+,	O
+are	O
+discussed	O
+.	O
+
+RESULTS	O
+:	O
+Acetabular	O
+index	O
+returned	O
+to	O
+normal	O
+gradually	O
+as	O
+the	O
+time	O
+went	O
+by	O
+and	O
+significantly	O
+within	O
+one	O
+year	O
+after	O
+the	O
+reduction	O
+of	O
+developmental	O
+dislocation	O
+of	O
+the	O
+hip	O
+.	O
+
+Recently	O
+,	O
+extremely	O
+high	O
+levels	O
+of	O
+endothelin	B-GENE
+-	I-GENE
+1	I-GENE
+(	O
+ET	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+were	O
+detected	O
+in	O
+the	O
+pericardial	O
+fluid	O
+of	O
+patients	O
+undergoing	O
+cardiac	O
+surgery	O
+.	O
+
+Consequently	O
+,	O
+it	O
+is	O
+not	O
+known	O
+how	O
+knee	O
+loading	O
+changes	O
+following	O
+ACL	O
+transection	O
+,	O
+and	O
+how	O
+it	O
+contributes	O
+to	O
+cartilage	O
+degeneration	O
+.	O
+
+We	O
+show	O
+that	O
+the	O
+surfaces	O
+of	O
+tracheal	O
+cartilage	O
+matrix	O
+are	O
+collagen	B-GENE
+-	O
+rich	O
+and	O
+surround	O
+a	O
+proteoglycan	O
+-	O
+rich	O
+core	O
+.	O
+
+Comparative	O
+mapping	O
+of	O
+the	O
+Brassica	B-GENE
+S	I-GENE
+locus	I-GENE
+region	I-GENE
+and	O
+its	O
+homeolog	O
+in	O
+Arabidopsis	O
+.	O
+
+Roles	O
+of	O
+the	O
+Candida	B-GENE
+albicans	I-GENE
+mitogen	I-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+homolog	I-GENE
+,	O
+Cek1p	B-GENE
+,	O
+in	O
+hyphal	O
+development	O
+and	O
+systemic	O
+candidiasis	O
+.	O
+
+Neither	O
+the	O
+reaction	O
+of	O
+monosaccharides	O
+nor	O
+the	O
+disaccharides	O
+with	O
+beta	O
+-	O
+alanine	O
+resulted	O
+in	O
+the	O
+formation	O
+of	O
+maltol	O
+.	O
+
+In	O
+most	O
+subjects	O
+,	O
+markers	O
+of	O
+bone	O
+formation	O
+and	O
+resorption	O
+were	O
+normal	O
+.	O
+
+Analysis	O
+of	O
+a	O
+Mac1p	B-GENE
+mutant	I-GENE
+,	O
+refractile	O
+for	O
+copper	O
+-	O
+dependent	O
+repression	O
+of	O
+the	O
+Cu	B-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+transport	I-GENE
+genes	I-GENE
+,	O
+showed	O
+an	O
+aberrant	O
+pattern	O
+of	O
+CUP1	B-GENE
+expression	O
+and	O
+copper	O
+sensitivity	O
+.	O
+
+The	O
+DNA	O
+sequencing	O
+of	O
+the	O
+recombinant	O
+clones	O
+revealed	O
+the	O
+expression	O
+of	O
+RXR	B-GENE
+alpha	I-GENE
+and	O
+RXR	B-GENE
+beta	I-GENE
+.	O
+
+A	O
+stratified	O
+random	O
+sample	O
+of	O
+20	O
+active	O
+employees	O
+from	O
+a	O
+cohort	O
+of	O
+phenoxy	O
+herbicide	O
+workers	O
+was	O
+selected	O
+in	O
+1995	O
+for	O
+determining	O
+PCDD	O
+and	O
+PCDF	O
+congeners	O
+in	O
+blood	O
+lipids	O
+to	O
+assess	O
+the	O
+extent	O
+of	O
+past	O
+PCDD	O
+and	O
+PCDF	O
+exposure	O
+in	O
+this	O
+cohort	O
+and	O
+whether	O
+that	O
+exposure	O
+might	O
+explain	O
+site	O
+-	O
+specific	O
+cancer	O
+findings	O
+in	O
+the	O
+total	O
+cohort	O
+.	O
+
+The	O
+clinical	O
+and	O
+laboratory	O
+features	O
+of	O
+72	O
+children	O
+with	O
+Henoch	O
+-	O
+Schonlein	O
+purpura	O
+(	O
+HSP	O
+)	O
+were	O
+examined	O
+to	O
+determine	O
+if	O
+there	O
+were	O
+associations	O
+between	O
+the	O
+laboratory	O
+indices	O
+-	O
+-	O
+including	O
+white	O
+blood	O
+cell	O
+(	O
+WBC	O
+)	O
+counts	O
+,	O
+serum	B-GENE
+C	I-GENE
+-	I-GENE
+reactive	I-GENE
+protein	I-GENE
+(	O
+CRP	B-GENE
+)	O
+levels	O
+,	O
+platelet	O
+(	O
+PLT	O
+)	O
+counts	O
+-	O
+-	O
+and	O
+the	O
+clinical	O
+manifestations	O
+of	O
+acute	O
+HSP	O
+.	O
+
+We	O
+provide	O
+community	O
+metabolic	O
+data	O
+that	O
+indicate	O
+that	O
+large	O
+changes	O
+in	O
+CO2	O
+concentration	O
+can	O
+occur	O
+in	O
+coral	O
+reef	O
+waters	O
+via	O
+biogeochemical	O
+processes	O
+not	O
+directly	O
+associated	O
+with	O
+photosynthesis	O
+,	O
+respiration	O
+,	O
+calcification	O
+,	O
+and	O
+CaCO3	O
+dissolution	O
+.	O
+
+In	O
+contrast	O
+to	O
+other	O
+known	O
+retroviruses	O
+,	O
+the	O
+FV	B-GENE
+pol	I-GENE
+genes	I-GENE
+are	O
+expressed	O
+via	O
+spliced	O
+transcripts	O
+.	O
+
+Substitution	O
+of	O
+bulky	O
+hydrophobic	O
+residues	O
+with	O
+charged	O
+residues	O
+within	O
+PEP1	B-GENE
+affects	O
+the	O
+fusion	O
+activity	O
+of	O
+the	O
+S	B-GENE
+protein	I-GENE
+without	O
+affecting	O
+processing	O
+and	O
+surface	O
+expression	O
+.	O
+
+Tributyltin	O
+and	O
+its	O
+breakdown	O
+products	O
+,	O
+mono	O
+-	O
+and	O
+di	O
+-	O
+butyltin	O
+,	O
+were	O
+determined	O
+in	O
+water	O
+birds	O
+collected	O
+from	O
+Lake	O
+Huron	O
+(	O
+the	O
+Great	O
+Lakes	O
+)	O
+,	O
+marine	O
+coastal	O
+United	O
+States	O
+,	O
+and	O
+the	O
+west	O
+coast	O
+of	O
+British	O
+Columbia	O
+,	O
+Canada	O
+.	O
+
+The	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+CD1	B-GENE
+gene	I-GENE
+contained	O
+the	O
+binding	O
+motifs	O
+for	O
+two	O
+cytokine	O
+-	O
+inducible	O
+transcription	O
+factors	O
+,	O
+NF	B-GENE
+-	I-GENE
+IL2	I-GENE
+-	I-GENE
+A	I-GENE
+and	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+.	O
+
+Fregnac	O
+,	O
+M	O
+.	O
+
+GLRaV	O
+-	O
+2	O
+is	O
+the	O
+only	O
+closterovirus	O
+,	O
+so	O
+far	O
+,	O
+that	O
+matches	O
+the	O
+genome	O
+organization	O
+of	O
+the	O
+type	O
+member	O
+of	O
+the	O
+group	O
+,	O
+BYV	O
+,	O
+and	O
+thus	O
+can	O
+be	O
+unambiguously	O
+classified	O
+as	O
+a	O
+definitive	O
+member	O
+of	O
+the	O
+genus	O
+Closterovirus	O
+.	O
+
+Demographic	O
+and	O
+clinical	O
+data	O
+were	O
+compared	O
+with	O
+a	O
+control	O
+group	O
+of	O
+339	O
+healthy	O
+age	O
+-	O
+matched	O
+women	O
+and	O
+with	O
+a	O
+sample	O
+of	O
+224	O
+women	O
+with	O
+wrist	O
+fracture	O
+.	O
+
+Identical	O
+results	O
+were	O
+obtained	O
+when	O
+transfections	O
+and	O
+mobility	O
+shift	O
+assays	O
+were	O
+performed	O
+in	O
+primary	O
+rat	O
+hepatocytes	O
+in	O
+which	O
+the	O
+endogenous	O
+ALS	B-GENE
+gene	I-GENE
+is	O
+expressed	O
+.	O
+
+This	O
+E	O
+box	O
+sequence	O
+(	O
+CACGTG	O
+)	O
+is	O
+identical	O
+to	O
+the	O
+binding	O
+element	O
+for	O
+USF	B-GENE
+(	O
+upstream	B-GENE
+stimulatory	I-GENE
+factor	I-GENE
+)	O
+,	O
+a	O
+member	O
+of	O
+the	O
+helix	B-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+family	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+Interferon	B-GENE
+beta	I-GENE
+therapy	O
+was	O
+discontinued	O
+for	O
+4	O
+weeks	O
+.	O
+
+We	O
+specially	O
+devised	O
+3	O
+types	O
+of	O
+turbo	O
+pumps	O
+,	O
+a	O
+centrifugal	O
+pump	O
+(	O
+CFP	O
+)	O
+,	O
+a	O
+mixed	O
+flow	O
+pump	O
+(	O
+MFP	O
+)	O
+,	O
+and	O
+an	O
+axial	O
+flow	O
+pump	O
+(	O
+AFP	O
+)	O
+,	O
+and	O
+analyzed	O
+their	O
+in	O
+vitro	O
+performance	O
+.	O
+
+Examination	O
+of	O
+the	O
+mitochondrial	B-GENE
+bc1	I-GENE
+complex	I-GENE
+crystal	I-GENE
+structure	I-GENE
+[	O
+Zhang	O
+,	O
+Z	O
+.	O
+,	O
+Huang	O
+,	O
+L	O
+.	O
+,	O
+Shulmeister	O
+,	O
+V	O
+.	O
+
+Two	O
+protease	O
+-	O
+resistant	O
+fragments	O
+spanning	O
+the	O
+N	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+halves	O
+of	O
+the	O
+nuclease	O
+were	O
+identified	O
+using	O
+different	O
+proteases	O
+which	O
+cleave	O
+the	O
+protein	O
+in	O
+the	O
+same	O
+region	O
+.	O
+
+The	O
+side	O
+-	O
+to	O
+-	O
+side	O
+difference	O
+was	O
+statistically	O
+significant	O
+at	O
+EXT	O
+30	O
+degrees	O
+/	O
+s	O
+and	O
+60	O
+degrees	O
+/	O
+s	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+women	O
+who	O
+want	O
+or	O
+require	O
+conservative	O
+management	O
+of	O
+grade	O
+4	O
+prolapse	O
+and	O
+are	O
+unable	O
+to	O
+retain	O
+a	O
+single	O
+pessary	O
+,	O
+the	O
+placement	O
+of	O
+two	O
+pessaries	O
+often	O
+will	O
+be	O
+successful	O
+.	O
+
+Rev	B-GENE
+-	O
+erbAalpha	B-GENE
+/	I-GENE
+beta	I-GENE
+)	O
+,	O
+Mxi	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+Mad	B-GENE
+bHLH	O
+-	O
+zip	O
+proteins	O
+and	O
+the	O
+oncoproteins	O
+PLZF	B-GENE
+and	O
+LAZ3	B-GENE
+/	O
+BCL6	B-GENE
+is	O
+mediated	O
+by	O
+the	O
+corepressors	O
+N	B-GENE
+-	I-GENE
+CoR	I-GENE
+and	O
+SMRT	B-GENE
+.	O
+
+The	O
+ParaSight	O
+-	O
+F	O
+test	O
+alone	O
+was	O
+used	O
+to	O
+monitor	O
+serum	O
+antigen	O
+levels	O
+after	O
+treatment	O
+in	O
+24	O
+patients	O
+.	O
+
+The	O
+purified	O
+recombinant	O
+protein	O
+was	O
+assayed	O
+for	O
+its	O
+enzyme	O
+activity	O
+by	O
+monitoring	O
+transfer	O
+of	O
+[	O
+3H	O
+]	O
+methyl	O
+groups	O
+from	O
+the	O
+substrate	O
+DNA	O
+to	O
+the	O
+MGMT	B-GENE
+protein	I-GENE
+;	O
+the	O
+activity	O
+was	O
+found	O
+to	O
+be	O
+stable	O
+at	O
+90	O
+degrees	O
+C	O
+for	O
+at	O
+least	O
+30	O
+min	O
+.	O
+
+A	O
+deproteinization	O
+procedure	O
+was	O
+coupled	O
+with	O
+a	O
+reversed	O
+-	O
+phase	O
+HPLC	O
+separation	O
+using	O
+a	O
+250x4	O
+.	O
+6	O
+mm	O
+I	O
+.	O
+D	O
+.	O
+
+Elimination	O
+of	O
+the	O
+inducible	O
+response	O
+requires	O
+simultaneous	O
+mutation	O
+of	O
+both	O
+sequences	O
+,	O
+however	O
+,	O
+in	O
+the	O
+presence	O
+of	O
+an	O
+intact	O
+EpRE	O
+the	O
+upstream	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+is	O
+irrelevant	O
+to	O
+induction	O
+.	O
+
+Three	O
+high	B-GENE
+mobility	I-GENE
+group	I-GENE
+-	I-GENE
+like	I-GENE
+sequences	I-GENE
+within	O
+a	O
+48	O
+-	O
+base	O
+pair	O
+enhancer	O
+of	O
+the	O
+Col2a1	B-GENE
+gene	I-GENE
+are	O
+required	O
+for	O
+cartilage	O
+-	O
+specific	O
+expression	O
+in	O
+vivo	O
+.	O
+
+The	O
+sequence	O
+contains	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+1744	O
+nt	O
+in	O
+the	O
+virus	O
+-	O
+sense	O
+strand	O
+,	O
+a	O
+3	O
+'	O
+untranslated	O
+region	O
+of	O
+1360	O
+nt	O
+and	O
+a	O
+3	O
+'	O
+poly	O
+(	O
+A	O
+)	O
+tail	O
+.	O
+
+A	O
+phylogenetic	O
+analysis	O
+of	O
+the	O
+reverse	B-GENE
+transcriptase	I-GENE
+domain	I-GENE
+confirms	O
+our	O
+differential	O
+genetic	O
+assessment	O
+that	O
+Cyclops	B-GENE
+from	O
+pea	O
+is	O
+a	O
+novel	O
+element	O
+with	O
+no	O
+specific	O
+relationship	O
+to	O
+the	O
+previously	O
+described	O
+Gypsy	B-GENE
+-	I-GENE
+like	I-GENE
+elements	I-GENE
+from	O
+plants	O
+.	O
+
+At	O
+physiological	O
+doses	O
+,	O
+either	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+I	I-GENE
+(	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+)	O
+or	O
+insulin	B-GENE
+turned	O
+out	O
+to	O
+be	O
+as	O
+potent	O
+as	O
+dibutyryl	O
+cAMP	O
+(	O
+dbcAMP	O
+)	O
+in	O
+increasing	O
+UCP1	B-GENE
+gene	I-GENE
+transcription	O
+rate	O
+(	O
+1	O
+h	O
+)	O
+and	O
+also	O
+UCP1	B-GENE
+mRNA	I-GENE
+accumulation	O
+(	O
+3	O
+h	O
+)	O
+,	O
+their	O
+maximal	O
+effect	O
+(	O
+15	O
+-	O
+fold	O
+increase	O
+)	O
+reached	O
+upon	O
+treatment	O
+for	O
+24	O
+h	O
+.	O
+
+In	O
+addition	O
+,	O
+insulin	B-GENE
+induced	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+DNA	O
+binding	O
+activity	O
+,	O
+this	O
+effect	O
+being	O
+totally	O
+prevented	O
+in	O
+the	O
+presence	O
+of	O
+MEK	B-GENE
+-	I-GENE
+1	I-GENE
+inhibitor	O
+.	O
+
+Essentially	O
+,	O
+2	O
+'	O
+-	O
+O	O
+-	O
+methyl	O
+oligoribonucleotides	O
+(	O
+2	O
+'	O
+OMeRNA	O
+)	O
+were	O
+delivered	O
+to	O
+the	O
+nuclei	O
+of	O
+primary	O
+mdx	O
+myoblasts	O
+in	O
+culture	O
+.	O
+
+Regulation	O
+of	O
+the	O
+human	O
+p21	B-GENE
+/	O
+WAF1	B-GENE
+/	O
+Cip1	B-GENE
+promoter	O
+in	O
+hepatic	O
+cells	O
+by	O
+functional	O
+interactions	O
+between	O
+Sp1	B-GENE
+and	O
+Smad	B-GENE
+family	I-GENE
+members	I-GENE
+.	O
+
+RESULTS	O
+:	O
+We	O
+isolated	O
+a	O
+C	O
+.	O
+elegans	O
+cDNA	O
+that	O
+encoded	O
+a	O
+protein	O
+which	O
+was	O
+similar	O
+to	O
+,	O
+but	O
+not	O
+exactly	O
+homologous	O
+with	O
+mammalian	O
+p120	B-GENE
+Ras	B-GENE
+-	O
+GAP	B-GENE
+.	O
+
+The	O
+weak	O
+base	O
+ketoconazole	O
+showed	O
+complete	O
+dissolution	O
+from	O
+a	O
+tablet	O
+formulation	O
+in	O
+Simulated	O
+Gastric	O
+Fluid	O
+without	O
+pepsin	B-GENE
+(	O
+SGFsp	O
+)	O
+within	O
+30	O
+minutes	O
+,	O
+70	O
+%	O
+dissolution	O
+in	O
+2	O
+hours	O
+under	O
+fed	O
+state	O
+simulated	O
+upper	O
+jejunal	O
+conditions	O
+but	O
+only	O
+6	O
+%	O
+dissolution	O
+in	O
+2	O
+hours	O
+under	O
+fasted	O
+state	O
+conditions	O
+.	O
+
+In	O
+mammals	O
+,	O
+the	O
+Rb	B-GENE
+protein	I-GENE
+interacts	O
+specifically	O
+with	O
+D	B-GENE
+-	I-GENE
+type	I-GENE
+cyclins	I-GENE
+and	O
+regulates	O
+cell	O
+proliferation	O
+by	O
+binding	O
+and	O
+inhibiting	O
+E2F	B-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+signals	O
+obtained	O
+by	O
+ligation	O
+of	O
+the	O
+TCR	B-GENE
+,	O
+T	O
+cells	O
+need	O
+additional	O
+,	O
+co	O
+-	O
+stimulatory	O
+signals	O
+to	O
+be	O
+activated	O
+.	O
+
+Moreover	O
+,	O
+the	O
+observation	O
+of	O
+enhanced	O
+luteal	B-GENE
+HSP	I-GENE
+-	I-GENE
+27	I-GENE
+phosphorylation	O
+in	O
+vivo	O
+,	O
+in	O
+late	O
+pregnancy	O
+,	O
+when	O
+PKC	B-GENE
+-	I-GENE
+delta	I-GENE
+is	O
+abundant	O
+and	O
+active	O
+,	O
+suggests	O
+that	O
+select	O
+PKC	B-GENE
+family	I-GENE
+members	I-GENE
+contribute	O
+to	O
+sHSP	B-GENE
+phosphorylation	O
+events	O
+in	O
+vivo	O
+.	O
+
+We	O
+characterized	O
+the	O
+structure	O
+of	O
+this	O
+leader	O
+mRNA	O
+by	O
+using	O
+the	O
+program	O
+Mfold	O
+and	O
+a	O
+combination	O
+of	O
+nested	O
+and	O
+internal	O
+deletions	O
+transcriptionally	O
+fused	O
+to	O
+a	O
+promoterless	O
+lac	B-GENE
+operon	I-GENE
+.	O
+
+The	O
+importance	O
+of	O
+these	O
+sites	O
+for	O
+transcriptional	O
+activation	O
+was	O
+studied	O
+by	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+followed	O
+by	O
+promoter	O
+function	O
+analysis	O
+of	O
+the	O
+mutants	O
+with	O
+a	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+reporter	I-GENE
+system	O
+.	O
+
+Routine	O
+blood	O
+examination	O
+showed	O
+leukocytosis	O
+,	O
+thrombocytopenia	O
+,	O
+positive	O
+CRP	B-GENE
+,	O
+and	O
+elevated	O
+myocardial	O
+enzymes	O
+.	O
+
+Previous	O
+studies	O
+have	O
+suggested	O
+that	O
+moderate	O
+cooling	O
+increases	O
+the	O
+responsiveness	O
+of	O
+vascular	B-GENE
+alpha2	I-GENE
+-	I-GENE
+adrenoceptors	I-GENE
+.	O
+
+Two	O
+members	O
+of	O
+the	O
+Cbl	B-GENE
+family	I-GENE
+have	O
+since	O
+been	O
+defined	O
+in	O
+mammals	O
+(	O
+c	B-GENE
+-	I-GENE
+Cbl	I-GENE
+and	O
+Cbl	B-GENE
+-	I-GENE
+b	I-GENE
+)	O
+,	O
+one	O
+in	O
+C	O
+.	O
+elegans	O
+(	O
+Sli	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+one	O
+in	O
+Drosophila	O
+(	O
+D	B-GENE
+-	I-GENE
+Cbl	I-GENE
+)	O
+.	O
+
+Anti	B-GENE
+-	I-GENE
+PTB	I-GENE
+antibodies	I-GENE
+did	O
+not	O
+inhibit	O
+the	O
+binding	O
+of	O
+PTB	B-GENE
+to	O
+RNA	O
+because	O
+they	O
+were	O
+able	O
+to	O
+supershift	O
+RNA	B-GENE
+-	I-GENE
+PTB	I-GENE
+complexes	I-GENE
+.	O
+
+The	O
+use	O
+of	O
+antibodies	O
+to	O
+the	O
+polypyrimidine	B-GENE
+tract	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+PTB	B-GENE
+)	O
+to	O
+analyze	O
+the	O
+protein	O
+components	O
+that	O
+assemble	O
+on	O
+alternatively	O
+spliced	O
+pre	O
+-	O
+mRNAs	O
+that	O
+use	O
+distant	O
+branch	O
+points	O
+.	O
+
+The	O
+therapeutic	O
+use	O
+of	O
+botulinum	B-GENE
+toxin	I-GENE
+(	O
+Botox	B-GENE
+)	O
+is	O
+increasing	O
+in	O
+popularity	O
+.	O
+
+The	O
+viral	B-GENE
+oncoprotein	I-GENE
+E1A	I-GENE
+inhibits	O
+NFAT	B-GENE
+-	O
+dependent	O
+transactivation	O
+in	O
+a	O
+p300	B-GENE
+-	O
+dependent	O
+manner	O
+.	O
+
+We	O
+have	O
+applied	O
+the	O
+mRNA	O
+differential	O
+display	O
+method	O
+to	O
+compare	O
+and	O
+analyze	O
+mRNAs	O
+prepared	O
+from	O
+five	O
+normal	O
+nasopharyngeal	O
+epithelial	O
+cell	O
+cultures	O
+and	O
+five	O
+nasopharyngeal	O
+carcinoma	O
+cell	O
+lines	O
+.	O
+
+Similar	O
+experiments	O
+with	O
+TR	B-GENE
+support	O
+the	O
+high	O
+affinity	O
+of	O
+RIP140	B-GENE
+to	O
+the	O
+RXR	B-GENE
+subunit	I-GENE
+and	O
+also	O
+suggest	O
+that	O
+either	O
+partner	O
+in	O
+the	O
+TR	B-GENE
+/	O
+RXR	B-GENE
+heterodimer	O
+can	O
+independently	O
+respond	O
+to	O
+ligand	O
+.	O
+
+SETTING	O
+:	O
+University	O
+hospital	O
+-	O
+based	O
+,	O
+tertiary	O
+care	O
+infertility	O
+center	O
+.	O
+
+RESULT	O
+(	O
+S	O
+)	O
+:	O
+In	O
+patients	O
+with	O
+elevated	O
+FSH	B-GENE
+levels	O
+on	O
+cycle	O
+day	O
+3	O
+,	O
+a	O
+low	O
+oocyte	O
+yield	O
+was	O
+achieved	O
+(	O
+7	O
+versus	O
+11	O
+)	O
+and	O
+a	O
+high	O
+number	O
+of	O
+ampules	O
+of	O
+hMG	B-GENE
+was	O
+necessary	O
+(	O
+56	O
+versus	O
+33	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+Of	O
+the	O
+patients	O
+with	O
+IS	O
+,	O
+67	O
+%	O
+had	O
+significantly	O
+greater	O
+values	O
+of	O
+directional	O
+preponderance	O
+on	O
+the	O
+OVAR	O
+test	O
+(	O
+a	O
+measure	O
+of	O
+otolith	O
+system	O
+imbalance	O
+)	O
+compared	O
+with	O
+control	O
+subjects	O
+.	O
+
+In	O
+the	O
+ePTFE	O
+specimens	O
+,	O
+tissue	O
+coverage	O
+had	O
+increased	O
+.	O
+
+As	O
+predicted	O
+by	O
+the	O
+Wing	O
+and	O
+Kristofferson	O
+model	O
+,	O
+the	O
+durations	O
+of	O
+successive	O
+ISIs	O
+tended	O
+to	O
+be	O
+negatively	O
+correlated	O
+.	O
+
+We	O
+found	O
+the	O
+following	O
+:	O
+Specific	O
+mutations	O
+affected	O
+the	O
+precise	O
+carbohydrate	O
+structure	O
+and	O
+folding	O
+of	O
+the	O
+HA	B-GENE
+trimer	I-GENE
+.	O
+
+The	O
+results	O
+show	O
+that	O
+ROS	O
+production	O
+by	O
+viable	O
+spermatozoa	O
+is	O
+highly	O
+correlated	O
+with	O
+the	O
+concentration	O
+of	O
+PMN	B-GENE
+elastase	I-GENE
+and	O
+the	O
+number	O
+of	O
+both	O
+peroxidase	B-GENE
+-	O
+positive	O
+and	O
+round	O
+cells	O
+.	O
+
+Yeast	B-GENE
+U1	I-GENE
+snRNP	I-GENE
+is	O
+considerably	O
+more	O
+complex	O
+than	O
+its	O
+metazoan	O
+counterpart	O
+,	O
+which	O
+suggests	O
+possible	O
+differences	O
+between	O
+yeast	O
+and	O
+metazoa	O
+in	O
+early	O
+splicing	O
+events	O
+.	O
+
+Yeast	B-GENE
+U1	I-GENE
+snRNP	I-GENE
+therefore	O
+contains	O
+16	O
+different	O
+proteins	O
+,	O
+including	O
+seven	O
+snRNP	B-GENE
+core	I-GENE
+proteins	I-GENE
+,	O
+three	O
+homologues	O
+of	O
+the	O
+metazoan	B-GENE
+U1	I-GENE
+snRNP	I-GENE
+-	I-GENE
+specific	I-GENE
+proteins	I-GENE
+,	O
+and	O
+six	O
+yeast	B-GENE
+-	I-GENE
+specific	I-GENE
+U1	I-GENE
+snRNP	I-GENE
+proteins	I-GENE
+.	O
+
+After	O
+the	O
+first	O
+cycle	O
+,	O
+18	O
+cases	O
+were	O
+treated	O
+at	O
+dose	O
+level	O
+1	O
+,	O
+after	O
+a	O
+second	O
+cycle	O
+,	O
+13	O
+cases	O
+were	O
+treated	O
+at	O
+dose	O
+level	O
+2	O
+.	O
+
+The	O
+opioid	O
+antagonist	O
+naltrexone	O
+(	O
+0	O
+.	O
+01	O
+-	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+)	O
+antagonized	O
+the	O
+discriminative	O
+stimulus	O
+effects	O
+of	O
+heroin	O
+,	O
+but	O
+naltrexone	O
+at	O
+doses	O
+up	O
+to	O
+10	O
+mg	O
+/	O
+kg	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+discriminative	O
+stimulus	O
+effects	O
+of	O
+cocaine	O
+.	O
+
+In	O
+this	O
+study	O
+we	O
+examined	O
+hepatic	O
+stellate	O
+cell	O
+regulation	O
+of	O
+M6P	B-GENE
+/	O
+IGFIIR	B-GENE
+expression	O
+and	O
+found	O
+that	O
+M6P	B-GENE
+/	O
+IGFIIR	B-GENE
+mRNA	O
+transcript	O
+levels	O
+increased	O
+in	O
+stellate	O
+cells	O
+from	O
+rats	O
+exposed	O
+to	O
+carbon	O
+tetrachloride	O
+(	O
+CCl4	O
+)	O
+,	O
+a	O
+potent	O
+fibrogenic	O
+stimulant	O
+.	O
+
+One	O
+cDNA	O
+clone	O
+designated	O
+NCoA	O
+-	O
+62	O
+,	O
+encoded	O
+a	O
+62	O
+,	O
+000	O
+-	O
+Da	O
+protein	O
+that	O
+is	O
+highly	O
+related	O
+to	O
+BX42	B-GENE
+,	O
+a	O
+Drosophila	O
+melanogaster	O
+nuclear	O
+protein	O
+involved	O
+in	O
+ecdysone	O
+-	O
+stimulated	O
+gene	O
+expression	O
+.	O
+
+These	O
+widely	O
+expressed	O
+proteins	O
+share	O
+a	O
+C	O
+-	O
+terminal	O
+region	O
+that	O
+bears	O
+significant	O
+sequence	O
+homology	O
+to	O
+a	O
+group	O
+of	O
+GDP	B-GENE
+/	I-GENE
+GTP	I-GENE
+exchange	I-GENE
+proteins	I-GENE
+for	O
+the	O
+Rab3	B-GENE
+family	I-GENE
+of	O
+small	B-GENE
+GTP	I-GENE
+binding	I-GENE
+proteins	I-GENE
+.	O
+
+Whereas	O
+p82	B-GENE
+expression	O
+had	O
+no	O
+effect	O
+on	O
+ERK2	B-GENE
+activation	O
+by	O
+p126	B-GENE
+,	O
+p70	B-GENE
+completely	O
+abrogated	O
+this	O
+activity	O
+.	O
+
+The	O
+pre	O
+-	O
+mRNA	O
+splicing	O
+factor	O
+U2AF	B-GENE
+(	O
+U2	B-GENE
+small	I-GENE
+nuclear	I-GENE
+ribonucleoprotein	I-GENE
+particle	I-GENE
+[	I-GENE
+snRNP	I-GENE
+]	I-GENE
+auxiliary	I-GENE
+factor	I-GENE
+)	O
+plays	O
+a	O
+critical	O
+role	O
+in	O
+3	O
+'	O
+splice	O
+site	O
+selection	O
+.	O
+
+The	O
+brackets	O
+were	O
+bonded	O
+to	O
+100	O
+freshly	O
+extracted	O
+bovine	O
+incisors	O
+,	O
+and	O
+,	O
+after	O
+storage	O
+in	O
+tap	O
+water	O
+at	O
+room	O
+temperature	O
+for	O
+24	O
+hours	O
+,	O
+they	O
+were	O
+subsequently	O
+tested	O
+in	O
+a	O
+shear	O
+mode	O
+using	O
+a	O
+universal	O
+testing	O
+machine	O
+.	O
+
+Exercise	O
+training	O
+has	O
+become	O
+increasingly	O
+important	O
+in	O
+the	O
+treatment	O
+of	O
+heart	O
+failure	O
+patients	O
+.	O
+
+The	O
+growth	O
+of	O
+Aer	O
+.	O
+hydrophila	O
+in	O
+filter	O
+-	O
+sterilized	O
+lettuce	O
+extract	O
+was	O
+completely	O
+inhibited	O
+by	O
+0	O
+.	O
+1	O
+%	O
+(	O
+v	O
+/	O
+v	O
+)	O
+BMC	O
+whereas	O
+that	O
+of	O
+Ps	O
+.	O
+fluorescens	O
+was	O
+not	O
+significantly	O
+affected	O
+by	O
+1	O
+%	O
+(	O
+v	O
+/	O
+v	O
+)	O
+BMC	O
+.	O
+
+Despite	O
+continuous	O
+compliance	O
+,	O
+unexplained	O
+resurgence	O
+of	O
+serum	O
+ferritin	B-GENE
+levels	O
+occurred	O
+in	O
+4	O
+/	O
+7	O
+patients	O
+of	O
+the	O
+'	O
+veteran	O
+'	O
+group	O
+after	O
+4	O
+-	O
+5	O
+years	O
+on	O
+L1	O
+.	O
+
+Hematocrit	O
+and	O
+PaO2	O
+did	O
+not	O
+change	O
+.	O
+
+Regulation	O
+of	O
+myosin	B-GENE
+phosphatase	I-GENE
+activity	O
+involves	O
+changes	O
+in	O
+subunit	O
+interactions	O
+,	O
+although	O
+molecular	O
+mechanisms	O
+are	O
+not	O
+defined	O
+.	O
+
+Commutative	O
+saccadic	O
+generator	O
+is	O
+sufficient	O
+to	O
+control	O
+a	O
+3	O
+-	O
+D	O
+ocular	O
+plant	O
+with	O
+pulleys	O
+.	O
+
+The	O
+virus	O
+-	O
+associated	O
+VAI	B-GENE
+RNA	O
+of	O
+adenovirus	O
+is	O
+a	O
+small	O
+highly	O
+structured	O
+RNA	O
+that	O
+is	O
+required	O
+for	O
+the	O
+efficient	O
+translation	O
+of	O
+cellular	O
+and	O
+viral	O
+mRNAs	O
+at	O
+late	O
+times	O
+after	O
+infection	O
+.	O
+
+Structure	O
+of	O
+the	O
+gene	O
+encoding	O
+the	O
+human	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+inhibitor	O
+p18	B-GENE
+and	O
+mutational	O
+analysis	O
+in	O
+breast	O
+cancer	O
+.	O
+
+The	O
+YccA	B-GENE
+protein	I-GENE
+was	O
+found	O
+to	O
+be	O
+degraded	O
+in	O
+an	O
+FtsH	B-GENE
+-	O
+dependent	O
+manner	O
+in	O
+vivo	O
+and	O
+in	O
+vitro	O
+,	O
+whereas	O
+the	O
+YccA11	B-GENE
+mutant	I-GENE
+protein	I-GENE
+,	O
+lacking	O
+eight	O
+amino	O
+acid	O
+residues	O
+within	O
+the	O
+amino	O
+-	O
+terminal	O
+cytoplasmic	O
+domain	O
+,	O
+was	O
+refractory	O
+to	O
+the	O
+degradation	O
+.	O
+
+The	O
+major	O
+type	O
+involves	O
+activator	O
+proteins	O
+that	O
+bind	O
+to	O
+DNA	O
+adjacent	O
+to	O
+where	O
+the	O
+RNA	B-GENE
+polymerase	I-GENE
+(	O
+RNAP	B-GENE
+)	O
+holoenzyme	O
+binds	O
+,	O
+usually	O
+assisting	O
+in	O
+recruitment	O
+of	O
+the	O
+RNAP	B-GENE
+to	O
+the	O
+promoter	O
+.	O
+
+A	O
+conserved	O
+role	O
+for	O
+L1	B-GENE
+as	O
+a	O
+transmembrane	O
+link	O
+between	O
+neuronal	O
+adhesion	O
+and	O
+membrane	O
+cytoskeleton	O
+assembly	O
+.	O
+
+Atmospheric	O
+benzene	O
+,	O
+urinary	O
+muconic	O
+acid	O
+(	O
+tt	O
+-	O
+MA	O
+)	O
+and	O
+leukocyte	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+activity	O
+(	O
+LAPA	O
+)	O
+were	O
+evaluated	O
+among	O
+66	O
+car	O
+mechanics	O
+,	O
+34	O
+road	O
+tanker	O
+drivers	O
+,	O
+and	O
+28	O
+nonexposed	O
+workers	O
+.	O
+
+It	O
+contains	O
+a	O
+5	O
+'	O
+-	O
+noncoding	O
+region	O
+(	O
+NCR	O
+)	O
+of	O
+73	O
+nucleotides	O
+,	O
+five	O
+open	O
+reading	O
+frames	O
+(	O
+ORFs	O
+1	O
+to	O
+5	O
+)	O
+which	O
+encode	O
+proteins	O
+with	O
+M	O
+(	O
+r	O
+)	O
+160	B-GENE
+kDa	I-GENE
+RNA	I-GENE
+-	I-GENE
+dependent	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+(	I-GENE
+ORF1	I-GENE
+)	I-GENE
+,	O
+26	B-GENE
+kDa	I-GENE
+movement	I-GENE
+protein	I-GENE
+1	I-GENE
+(	I-GENE
+ORF2	I-GENE
+)	I-GENE
+,	O
+13	B-GENE
+kDa	I-GENE
+movement	I-GENE
+protein	I-GENE
+2	I-GENE
+(	I-GENE
+ORF3	I-GENE
+)	I-GENE
+,	O
+10	B-GENE
+kDa	I-GENE
+movement	I-GENE
+protein	I-GENE
+3	I-GENE
+(	I-GENE
+ORF4	I-GENE
+)	I-GENE
+,	O
+24	B-GENE
+kDa	I-GENE
+coat	I-GENE
+protein	I-GENE
+(	I-GENE
+OFR5	I-GENE
+)	I-GENE
+,	O
+and	O
+a	O
+3	O
+'	O
+NCR	O
+of	O
+76	O
+nucleotides	O
+.	O
+
+After	O
+profound	O
+normovolemic	O
+hemodilution	O
+(	O
+Hct	O
+9	O
+%	O
+)	O
+superiority	O
+of	O
+LV	O
+MC	O
+and	O
+LV	O
+diastolic	O
+properties	O
+was	O
+found	O
+,	O
+when	O
+myocardial	O
+oxygenation	O
+was	O
+supported	O
+by	O
+i	O
+.	O
+v	O
+.	O
+perflubron	O
+emulsion	O
+,	O
+a	O
+temporary	O
+O2	O
+carrier	O
+.	O
+
+These	O
+genes	O
+may	O
+represent	O
+interesting	O
+targets	O
+for	O
+new	O
+therapeutic	O
+strategies	O
+.	O
+
+It	O
+could	O
+also	O
+inhibit	O
+C1q	B-GENE
+-	O
+dependent	O
+haemolysis	O
+of	O
+both	O
+IgG	B-GENE
+-	O
+and	O
+IgM	B-GENE
+-	O
+sensitized	O
+erythrocytes	O
+.	O
+
+3	O
+)	O
+and	O
+one	O
+distal	O
+(	O
+-	O
+11	O
+.	O
+8	O
+/	O
+-	O
+10	O
+.	O
+9	O
+)	O
+,	O
+presented	O
+an	O
+enhancer	O
+activity	O
+in	O
+pituitary	O
+cells	O
+when	O
+placed	O
+upstream	O
+of	O
+the	O
+SV40	B-GENE
+promoter	I-GENE
+.	O
+
+3	O
+-	O
+-	O
+It	O
+is	O
+necessary	O
+to	O
+think	O
+about	O
+cosmetic	O
+consequences	O
+of	O
+the	O
+chinese	O
+flap	O
+and	O
+consider	O
+other	O
+possibilities	O
+of	O
+the	O
+flap	O
+choice	O
+.	O
+
+CONCLUSION	O
+:	O
+TNF	B-GENE
+alpha	I-GENE
+,	O
+TGF	B-GENE
+beta	I-GENE
+,	O
+PDGF	B-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+increased	O
+LDLr	B-GENE
+gene	I-GENE
+expression	O
+by	O
+increasing	O
+sterol	O
+-	O
+independent	O
+and	O
+mitogenesis	O
+-	O
+independent	O
+gene	O
+transcription	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+only	O
+one	O
+-	O
+half	O
+and	O
+one	O
+-	O
+third	O
+the	O
+size	O
+of	O
+the	O
+proteolipids	O
+from	O
+M	O
+.	O
+thermoautotrophicum	O
+and	O
+M	O
+.	O
+jannaschii	O
+,	O
+respectively	O
+.	O
+ahaK	B-GENE
+is	O
+expressed	O
+in	O
+Escherichia	O
+coli	O
+,	O
+and	O
+it	O
+is	O
+incorporated	O
+into	O
+the	O
+cytoplasmic	O
+membrane	O
+despite	O
+the	O
+different	O
+chemical	O
+natures	O
+of	O
+lipids	O
+from	O
+archaea	O
+and	O
+bacteria	O
+.	O
+
+In	O
+this	O
+report	O
+we	O
+studied	O
+the	O
+role	O
+of	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+in	O
+ErbB	B-GENE
+-	O
+mediated	O
+activation	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+MAPK	B-GENE
+)	O
+by	O
+overexpressing	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+mutants	I-GENE
+in	O
+COS	O
+-	O
+7	O
+cells	O
+.	O
+
+Osteoadherin	B-GENE
+is	O
+a	O
+recently	O
+described	O
+bone	O
+proteoglycan	O
+containing	O
+keratan	O
+sulfate	O
+.	O
+
+Intron	O
+8	O
+harbored	O
+a	O
+strong	O
+erythroid	O
+-	O
+specific	O
+enhancer	O
+activity	O
+which	O
+was	O
+orientation	O
+-	O
+dependent	O
+.	O
+
+The	O
+intron	O
+8	O
+enhancer	O
+region	O
+was	O
+not	O
+activated	O
+by	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+together	O
+with	O
+Sp1	B-GENE
+in	O
+transactivation	O
+experiments	O
+in	O
+COS	O
+-	O
+1	O
+cells	O
+indicating	O
+the	O
+involvement	O
+of	O
+a	O
+related	O
+Sp1	B-GENE
+protein	I-GENE
+or	O
+of	O
+another	O
+unidentified	O
+erythroid	O
+factor	O
+.	O
+
+The	O
+cleavage	O
+of	O
+Fak	B-GENE
+by	O
+caspases	B-GENE
+may	O
+thus	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+execution	O
+of	O
+the	O
+suicide	O
+program	O
+by	O
+disabling	O
+the	O
+anti	O
+-	O
+apoptotic	O
+function	O
+of	O
+Fak	B-GENE
+.	O
+
+Moreover	O
+,	O
+the	O
+mass	O
+estimated	O
+with	O
+the	O
+QCM	O
+response	O
+through	O
+the	O
+Sauerbrey	O
+equation	O
+and	O
+the	O
+mass	O
+which	O
+can	O
+be	O
+measured	O
+thanks	O
+to	O
+other	O
+analytical	O
+techniques	O
+,	O
+in	O
+our	O
+case	O
+an	O
+enzymatic	O
+assay	O
+,	O
+are	O
+different	O
+:	O
+the	O
+deposited	O
+mass	O
+is	O
+generally	O
+overestimated	O
+by	O
+the	O
+QCM	O
+.	O
+
+Transcription	O
+initiation	O
+occurred	O
+predominantly	O
+at	O
+the	O
+putative	O
+sigmaA	B-GENE
+-	I-GENE
+dependent	I-GENE
+promoter	I-GENE
+in	O
+exponentially	O
+growing	O
+cells	O
+and	O
+was	O
+induced	O
+under	O
+stress	O
+conditions	O
+.	O
+
+The	O
+genes	O
+encoding	O
+(	B-GENE
+2Fe	I-GENE
+-	I-GENE
+2S	I-GENE
+)	I-GENE
+plant	I-GENE
+-	I-GENE
+like	I-GENE
+ferredoxins	I-GENE
+were	O
+studied	O
+in	O
+the	O
+widely	O
+used	O
+cyanobacterium	O
+Synechocystis	O
+PCC6803	O
+.	O
+
+RNA	O
+of	O
+GBV	O
+-	O
+C	O
+was	O
+detected	O
+in	O
+14	O
+(	O
+18	O
+%	O
+)	O
+patients	O
+before	O
+BMT	O
+.	O
+
+A	O
+major	O
+pool	O
+of	O
+Dsg	B-GENE
+-	O
+plakoglobin	B-GENE
+complexes	O
+sedimented	O
+at	O
+8S	O
+and	O
+exhibited	O
+a	O
+1	O
+:	O
+1	O
+stoichiometry	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+the	O
+binding	O
+of	O
+CBF	B-GENE
+/	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+to	O
+the	O
+inverted	O
+CCAAT	O
+box	O
+is	O
+responsible	O
+for	O
+transcriptional	O
+activation	O
+of	O
+the	O
+nTPH	B-GENE
+gene	I-GENE
+.	O
+
+In	O
+macrophages	O
+,	O
+LPS	O
+-	O
+inducible	O
+HIV	O
+-	O
+1	O
+gene	O
+expression	O
+is	O
+mediated	O
+in	O
+part	O
+by	O
+binding	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+to	O
+identical	O
+tandem	O
+binding	O
+sites	O
+located	O
+within	O
+the	O
+long	O
+terminal	O
+repeat	O
+(	O
+LTR	O
+)	O
+.	O
+
+The	O
+influence	O
+of	O
+p53	B-GENE
+on	O
+cytokine	O
+-	O
+triggered	O
+Janus	B-GENE
+kinase	I-GENE
+-	O
+STAT	B-GENE
+signaling	O
+was	O
+investigated	O
+in	O
+human	O
+hepatoma	O
+Hep3B	O
+cell	O
+lines	O
+engineered	O
+to	O
+constitutively	O
+express	O
+the	O
+temperature	O
+-	O
+sensitive	O
+Val135	B-GENE
+mutant	I-GENE
+of	I-GENE
+p53	I-GENE
+.	O
+
+It	O
+can	O
+also	O
+be	O
+used	O
+to	O
+examine	O
+various	O
+laryngeal	O
+parameters	O
+obtained	O
+from	O
+videotaped	O
+endoscopic	O
+and	O
+stroboscopic	O
+examinations	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Two	O
+consecutive	O
+sets	O
+of	O
+transrectal	O
+ultrasound	O
+guided	O
+sextant	O
+biopsies	O
+of	O
+the	O
+prostate	O
+performed	O
+in	O
+a	O
+single	O
+office	O
+visit	O
+represent	O
+a	O
+cost	O
+-	O
+effective	O
+biopsy	O
+strategy	O
+for	O
+men	O
+presenting	O
+with	O
+an	O
+abnormal	O
+digital	O
+rectal	O
+examination	O
+and	O
+/	O
+or	O
+elevated	O
+serum	B-GENE
+PSA	I-GENE
+.	O
+
+Examination	O
+of	O
+nuclear	O
+magnetic	O
+resonance	O
+(	O
+NMR	O
+)	O
+spectra	O
+of	O
+a	O
+series	O
+of	O
+N	B-GENE
+-	I-GENE
+terminally	I-GENE
+truncated	I-GENE
+MIP	I-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+variants	I-GENE
+reveals	O
+that	O
+these	O
+proteins	O
+possess	O
+a	O
+range	O
+of	O
+ability	O
+to	O
+dimerize	O
+.	O
+
+Interestingly	O
+,	O
+PKA	B-GENE
+activity	O
+is	O
+dispensable	O
+in	O
+a	O
+strain	O
+lacking	O
+Msn2p	B-GENE
+and	O
+Msn4p	B-GENE
+activity	O
+.	O
+
+They	O
+also	O
+indicate	O
+that	O
+direct	O
+interactions	O
+between	O
+C	B-GENE
+/	I-GENE
+EBPs	I-GENE
+and	O
+specific	O
+Ets	B-GENE
+family	O
+members	O
+,	O
+together	O
+with	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+are	O
+important	O
+for	O
+eosinophil	O
+lineage	O
+determination	O
+.	O
+
+Recently	O
+,	O
+a	O
+human	B-GENE
+transcription	I-GENE
+elongation	I-GENE
+factor	I-GENE
+P	I-GENE
+-	I-GENE
+TEFb	I-GENE
+,	O
+consisting	O
+of	O
+CDK9	B-GENE
+kinase	I-GENE
+,	O
+cyclin	B-GENE
+T	I-GENE
+and	O
+other	O
+associated	O
+factors	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+interact	O
+with	O
+Tat	B-GENE
+to	O
+restore	O
+Tat	B-GENE
+activation	O
+in	O
+HeLa	O
+nuclear	O
+extract	O
+depleted	O
+of	O
+P	B-GENE
+-	I-GENE
+TEFb	I-GENE
+.	O
+
+We	O
+have	O
+used	O
+the	O
+hydrophobic	O
+repeats	O
+of	O
+the	O
+HSF1	B-GENE
+trimerization	I-GENE
+domain	I-GENE
+in	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+protein	O
+interaction	O
+assay	O
+to	O
+identify	O
+heat	B-GENE
+shock	I-GENE
+factor	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+(	O
+HSBP1	B-GENE
+)	O
+,	O
+a	O
+novel	O
+,	O
+conserved	O
+,	O
+76	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+that	O
+contains	O
+two	O
+extended	O
+arrays	O
+of	O
+hydrophobic	O
+repeats	O
+that	O
+interact	O
+with	O
+the	O
+HSF1	B-GENE
+heptad	I-GENE
+repeats	I-GENE
+.	O
+
+Genomic	O
+and	O
+cDNA	O
+clones	O
+homologous	O
+to	O
+the	O
+yeast	O
+GCN2	B-GENE
+eIF	B-GENE
+-	I-GENE
+2alpha	I-GENE
+kinase	O
+(	O
+yGCN2	O
+)	O
+were	O
+isolated	O
+from	O
+Drosophila	O
+melanogaster	O
+.	O
+
+The	O
+general	O
+recombination	O
+at	O
+a	O
+polarizing	O
+voltage	O
+of	O
+300	O
+V	O
+is	O
+less	O
+than	O
+2	O
+%	O
+for	O
+dose	O
+-	O
+rates	O
+up	O
+to	O
+about	O
+100	O
+mGy	O
+min	O
+-	O
+1	O
+.	O
+
+The	O
+low	O
+number	O
+of	O
+false	O
+positives	O
+indicates	O
+that	O
+our	O
+scheme	O
+would	O
+not	O
+confuse	O
+the	O
+radiologist	O
+by	O
+suggesting	O
+normal	O
+regions	O
+as	O
+suspicious	O
+.	O
+
+Strengthening	O
+the	O
+biological	O
+weapons	O
+convention	O
+and	O
+implications	O
+on	O
+the	O
+pharmaceutical	O
+and	O
+biotechnology	O
+industry	O
+.	O
+
+VirD2	B-GENE
+is	O
+one	O
+of	O
+the	O
+key	O
+Agrobacterium	O
+tumefaciens	O
+proteins	O
+involved	O
+in	O
+T	O
+-	O
+DNA	O
+processing	O
+and	O
+transfer	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+indicate	O
+that	O
+the	O
+VirD2	B-GENE
+omega	I-GENE
+domain	I-GENE
+is	O
+important	O
+for	O
+efficient	O
+T	O
+-	O
+DNA	O
+integration	O
+.	O
+
+The	O
+DHEAS	O
+levels	O
+in	O
+all	O
+stages	O
+of	O
+decreased	O
+BMD	O
+were	O
+significantly	O
+lower	O
+than	O
+those	O
+in	O
+the	O
+group	O
+with	O
+normal	O
+BMD	O
+.	O
+
+Orientation	O
+of	O
+the	O
+nuclear	O
+spin	O
+system	O
+by	O
+optical	O
+pumping	O
+causes	O
+an	O
+Overhauser	O
+shift	O
+of	O
+the	O
+excitonic	O
+energy	O
+levels	O
+proportional	O
+to	O
+the	O
+degree	O
+of	O
+nuclear	O
+orientation	O
+.	O
+
+Cystatin	B-GENE
+A	I-GENE
+,	O
+a	O
+cysteine	B-GENE
+proteinase	I-GENE
+inhibitor	O
+,	O
+is	O
+one	O
+of	O
+the	O
+precursor	O
+proteins	O
+of	O
+cornified	B-GENE
+cell	I-GENE
+envelope	I-GENE
+of	O
+keratinocytes	O
+and	O
+is	O
+expressed	O
+during	O
+the	O
+late	O
+stage	O
+of	O
+keratinocyte	O
+differentiation	O
+.	O
+
+A	O
+role	O
+for	O
+RalGDS	B-GENE
+and	O
+a	O
+novel	O
+Ras	B-GENE
+effector	O
+in	O
+the	O
+Ras	B-GENE
+-	O
+mediated	O
+inhibition	O
+of	O
+skeletal	O
+myogenesis	O
+.	O
+
+GTPase	B-GENE
+activating	O
+specificity	O
+of	O
+RGS12	B-GENE
+and	O
+binding	O
+specificity	O
+of	O
+an	O
+alternatively	O
+spliced	O
+PDZ	B-GENE
+(	O
+PSD	B-GENE
+-	I-GENE
+95	I-GENE
+/	O
+Dlg	B-GENE
+/	O
+ZO	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+domain	O
+.	O
+
+However	O
+,	O
+mutations	O
+in	O
+the	O
+HNF	B-GENE
+-	I-GENE
+4	I-GENE
+binding	I-GENE
+site	I-GENE
+on	O
+element	B-GENE
+CIIB	I-GENE
+and	O
+inhibition	O
+of	O
+HNF	B-GENE
+-	I-GENE
+4	I-GENE
+synthesis	O
+in	O
+HepG2	O
+cells	O
+by	O
+antisense	O
+HNF	B-GENE
+-	I-GENE
+4	I-GENE
+constructs	I-GENE
+decreased	O
+the	O
+apoCII	B-GENE
+promoter	I-GENE
+activity	O
+to	O
+25	O
+-	O
+40	O
+%	O
+of	O
+the	O
+control	O
+,	O
+indicating	O
+that	O
+HNF	B-GENE
+-	I-GENE
+4	I-GENE
+is	O
+a	O
+positive	O
+regulator	O
+of	O
+the	O
+apoCII	B-GENE
+gene	I-GENE
+.	O
+
+272	O
+,	O
+19107	O
+-	O
+19110	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+find	O
+that	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+can	O
+cause	O
+apoptosis	O
+in	O
+p53	B-GENE
+-	I-GENE
+/	I-GENE
+-	I-GENE
+tumour	O
+cells	O
+and	O
+further	O
+p300	B-GENE
+,	O
+which	O
+also	O
+functions	O
+as	O
+a	O
+co	O
+-	O
+activator	O
+for	O
+the	O
+E2F	B-GENE
+/	O
+DP	B-GENE
+heterodimer	O
+,	O
+enhances	O
+the	O
+apoptotic	O
+activity	O
+of	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Blocked	O
+shift	O
+/	O
+supershift	O
+analysis	O
+indicates	O
+that	O
+Fos	B-GENE
+family	I-GENE
+member	O
+proteins	O
+especially	O
+Fra	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+Fra	B-GENE
+-	I-GENE
+2	I-GENE
+are	O
+related	O
+to	O
+progression	O
+and	O
+no	O
+changes	O
+found	O
+in	O
+the	O
+Jun	B-GENE
+family	I-GENE
+member	O
+proteins	O
+although	O
+they	O
+are	O
+present	O
+in	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+/	I-GENE
+DNA	I-GENE
+binding	I-GENE
+complex	I-GENE
+.	O
+
+Initially	O
+,	O
+we	O
+observed	O
+that	O
+unmutated	O
+p53	B-GENE
+is	O
+strongly	O
+expressed	O
+in	O
+premalignant	O
+mammary	O
+glands	O
+and	O
+in	O
+mammary	O
+tumors	O
+derived	O
+from	O
+the	O
+MMTV	O
+-	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+strain	O
+.	O
+
+These	O
+data	O
+show	O
+that	O
+heterologous	O
+virus	O
+RNAs	O
+(	O
+BSMV	O
+)	O
+can	O
+serve	O
+as	O
+primer	O
+donors	O
+for	O
+MStV	O
+mRNA	O
+capped	O
+RNA	O
+-	O
+primed	O
+transcription	O
+in	O
+doubly	O
+infected	O
+plants	O
+.	O
+
+Human	O
+isoforms	O
+,	O
+designated	O
+1	O
+to	O
+4	O
+,	O
+differ	O
+from	O
+each	O
+other	O
+by	O
+the	O
+start	O
+codon	O
+used	O
+.	O
+
+Comparison	O
+of	O
+cDNA	O
+and	O
+genomic	O
+sequences	O
+shows	O
+that	O
+the	O
+ZNF189	B-GENE
+gene	I-GENE
+spans	O
+approximately	O
+11	O
+kb	O
+and	O
+is	O
+organized	O
+into	O
+at	O
+least	O
+four	O
+exons	O
+,	O
+the	O
+large	O
+3	O
+'	O
+-	O
+end	O
+exon	O
+coding	O
+for	O
+the	O
+complete	O
+zinc	O
+finger	O
+domain	O
+and	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+.	O
+
+The	O
+gp330	B-GENE
+/	O
+Megalin	B-GENE
+/	O
+LRP	B-GENE
+-	I-GENE
+2	I-GENE
+protein	O
+belongs	O
+to	O
+the	O
+low	B-GENE
+-	I-GENE
+density	I-GENE
+lipoprotein	I-GENE
+receptor	I-GENE
+gene	I-GENE
+family	I-GENE
+and	O
+is	O
+believed	O
+to	O
+function	O
+as	O
+an	O
+endocytic	O
+receptor	O
+for	O
+the	O
+uptake	O
+of	O
+lipoproteins	O
+and	O
+many	O
+other	O
+ligands	O
+.	O
+
+In	O
+the	O
+DNA	O
+recognition	O
+helix	O
+of	O
+finger	O
+II	O
+,	O
+the	O
+conserved	O
+Arg	O
+at	O
+position	O
+62	O
+(	O
+N	O
+-	O
+terminal	O
+side	O
+of	O
+the	O
+first	O
+zinc	O
+-	O
+coordinating	O
+histidine	O
+)	O
+was	O
+changed	O
+to	O
+a	O
+Leu	O
+or	O
+Gln	O
+.	O
+
+Dosage	O
+in	O
+both	O
+cases	O
+was	O
+0	O
+.	O
+2	O
+g	O
+/	O
+m2	O
+.	O
+
+Five	O
+additional	O
+copies	O
+of	O
+Lian	B-GENE
+elements	I-GENE
+were	O
+isolated	O
+,	O
+mapped	O
+by	O
+restriction	O
+digestion	O
+,	O
+and	O
+partially	O
+sequenced	O
+.	O
+
+Evolutionary	O
+relationships	O
+among	O
+putative	O
+RNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+RNA	I-GENE
+polymerases	I-GENE
+encoded	O
+by	O
+a	O
+mitochondrial	O
+virus	O
+-	O
+like	O
+RNA	O
+in	O
+the	O
+Dutch	O
+elm	O
+disease	O
+fungus	O
+,	O
+Ophiostoma	O
+novo	O
+-	O
+ulmi	O
+,	O
+by	O
+other	O
+viruses	O
+and	O
+virus	O
+-	O
+like	O
+RNAs	O
+and	O
+by	O
+the	O
+Arabidopsis	O
+mitochondrial	O
+genome	O
+.	O
+
+Role	O
+of	O
+the	O
+transcription	O
+start	O
+site	O
+core	O
+region	O
+and	O
+transcription	B-GENE
+factor	I-GENE
+YY1	I-GENE
+in	O
+Rous	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+long	I-GENE
+terminal	I-GENE
+repeat	I-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+Addition	O
+of	O
+Rap	O
+or	O
+KN62	O
+after	O
+exposure	O
+of	O
+cells	O
+to	O
+progesterone	O
+agonist	O
+Org	O
+2058	O
+had	O
+no	O
+effect	O
+on	O
+induction	O
+of	O
+CAT	B-GENE
+activity	O
+.	O
+
+The	O
+Dax	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+encodes	O
+a	O
+protein	O
+that	O
+is	O
+structurally	O
+related	O
+to	O
+members	O
+of	O
+the	O
+orphan	B-GENE
+nuclear	I-GENE
+receptor	I-GENE
+superfamily	I-GENE
+.	O
+
+He	O
+was	O
+administered	O
+recombinant	B-GENE
+IFN	I-GENE
+alpha	I-GENE
+-	I-GENE
+2b	I-GENE
+under	O
+the	O
+diagnosis	O
+of	O
+chronic	O
+hepatitis	O
+C	O
+.	O
+
+Regulation	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+therefore	O
+,	O
+involves	O
+the	O
+action	O
+of	O
+three	O
+protein	O
+kinase	O
+cascades	O
+that	O
+repress	O
+HSF1	B-GENE
+through	O
+phosphorylation	O
+of	O
+serine	O
+residues	O
+303	O
+,	O
+307	O
+,	O
+and	O
+363	O
+and	O
+may	O
+promote	O
+growth	O
+by	O
+suppressing	O
+the	O
+heat	O
+shock	O
+response	O
+.	O
+
+Clinical	O
+implication	O
+of	O
+protein	O
+levels	O
+of	O
+IL	B-GENE
+-	I-GENE
+5	I-GENE
+in	O
+induced	O
+sputum	O
+in	O
+asthmatic	O
+patients	O
+.	O
+
+In	O
+these	O
+cells	O
+,	O
+ras	B-GENE
+-	O
+induced	O
+transition	O
+is	O
+accompanied	O
+by	O
+a	O
+strong	O
+induction	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+binding	O
+activity	O
+along	O
+with	O
+increased	O
+expression	O
+of	O
+CD44	B-GENE
+mRNA	I-GENE
+and	O
+protein	O
+.	O
+
+This	O
+distribution	O
+implies	O
+that	O
+the	O
+polycistronic	O
+precursor	O
+is	O
+imported	O
+into	O
+the	O
+nucleolus	O
+for	O
+processing	O
+to	O
+the	O
+mature	O
+snoRNAs	O
+,	O
+and	O
+that	O
+the	O
+import	O
+or	O
+processing	O
+pathway	O
+involves	O
+coiled	O
+bodies	O
+.	O
+
+Suppressive	O
+therapy	O
+for	O
+thyroid	O
+nodules	O
+.	O
+
+Fourteen	O
+healthy	O
+male	O
+volunteers	O
+completed	O
+the	O
+study	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+Mg2	O
++	O
+,	O
+a	O
+hydrophobic	O
+exonuclease	O
+site	O
+dominates	O
+over	O
+the	O
+polymerase	O
+site	O
+for	O
+possession	O
+of	O
+the	O
+primer	O
+terminus	O
+.	O
+
+As	O
+the	O
+high	O
+-	O
+affinity	O
+Mg2	O
++	O
+binding	O
+sites	O
+are	O
+filled	O
+,	O
+the	O
+primer	O
+terminus	O
+migrates	O
+from	O
+the	O
+exonuclease	O
+site	O
+to	O
+a	O
+highly	O
+based	O
+stacked	O
+polymerase	O
+active	O
+site	O
+.	O
+
+One	O
+missense	O
+allele	O
+(	O
+P236S	O
+)	O
+with	O
+complete	O
+loss	O
+of	O
+function	O
+at	O
+30	O
+degreesC	O
+and	O
+four	O
+missense	O
+alleles	O
+(	O
+L173F	O
+,	O
+E225K	O
+,	O
+S269L	O
+and	O
+E274K	O
+)	O
+that	O
+conferred	O
+a	O
+temperature	O
+sensitive	O
+phenotype	O
+were	O
+identified	O
+.	O
+
+Structural	O
+analysis	O
+of	O
+the	O
+5	O
+'	O
+-	O
+regulatory	O
+region	O
+reveals	O
+that	O
+the	O
+c	B-GENE
+-	I-GENE
+met	I-GENE
+promoter	I-GENE
+lacks	O
+TATA	O
+or	O
+CAAT	O
+elements	O
+but	O
+has	O
+an	O
+extremely	O
+high	O
+G	O
+-	O
+C	O
+content	O
+and	O
+multiple	O
+Sp1	B-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+The	O
+report	O
+highlights	O
+the	O
+possible	O
+contribution	O
+of	O
+stress	O
+factors	O
+in	O
+the	O
+context	O
+of	O
+therapy	O
+resistant	O
+periodontal	O
+disease	O
+,	O
+and	O
+the	O
+results	O
+seem	O
+to	O
+be	O
+understandable	O
+within	O
+the	O
+context	O
+of	O
+a	O
+stress	O
+system	O
+disorder	O
+perspective	O
+.	O
+
+Acute	O
+pancreatitis	O
+is	O
+a	O
+rather	O
+common	O
+abdominal	O
+disorder	O
+.	O
+
+Each	O
+binding	O
+site	O
+,	O
+however	O
+,	O
+was	O
+different	O
+in	O
+its	O
+preference	O
+for	O
+binding	O
+partners	O
+.	O
+
+We	O
+isolated	O
+the	O
+human	B-GENE
+FGF	I-GENE
+-	I-GENE
+BP	I-GENE
+promoter	I-GENE
+and	O
+determined	O
+by	O
+deletion	O
+analysis	O
+that	O
+TPA	O
+regulatory	O
+elements	O
+were	O
+all	O
+contained	O
+in	O
+the	O
+first	O
+118	O
+base	O
+pairs	O
+upstream	O
+of	O
+the	O
+transcription	O
+start	O
+site	O
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+demonstrated	O
+specific	O
+nuclear	O
+protein	O
+binding	O
+to	O
+-	O
+85	O
+/	O
+-	O
+64	O
+,	O
+and	O
+single	O
+point	O
+mutations	O
+suggested	O
+important	O
+binding	O
+nucleotides	O
+between	O
+-	O
+79	O
+/	O
+-	O
+68	O
+with	O
+five	O
+critical	O
+bases	O
+between	O
+-	O
+74	O
+/	O
+-	O
+70	O
+(	O
+5	O
+'	O
+-	O
+CTCCT	O
+-	O
+3	O
+'	O
+)	O
+.	O
+
+"	O
+Complex	O
+partial	O
+"	O
+seizures	O
+.	O
+
+B	B-GENE
+cell	I-GENE
+antigen	I-GENE
+receptor	I-GENE
+(	O
+BCR	B-GENE
+)	O
+-	O
+mediated	O
+formation	O
+of	O
+a	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+-	O
+pp120	B-GENE
+complex	O
+and	O
+its	O
+inhibition	O
+by	O
+Fc	B-GENE
+gamma	I-GENE
+RIIB1	I-GENE
+-	O
+BCR	B-GENE
+coligation	O
+.	O
+
+Chem	O
+.	O
+,	O
+270	O
+:	O
+7117	O
+-	O
+7124	O
+,	O
+1995	O
+;	O
+and	O
+MT	O
+Hartsough	O
+et	O
+al	O
+.	O
+,	O
+J	O
+.	O
+
+Here	O
+we	O
+investigate	O
+the	O
+role	O
+of	O
+c	B-GENE
+-	I-GENE
+Cbl	I-GENE
+in	O
+development	O
+and	O
+homeostasis	O
+in	O
+mice	O
+by	O
+targeted	O
+disruption	O
+of	O
+the	O
+c	B-GENE
+-	I-GENE
+Cbl	I-GENE
+locus	I-GENE
+.	O
+c	B-GENE
+-	I-GENE
+Cbl	I-GENE
+-	O
+deficient	O
+mice	O
+were	O
+viable	O
+,	O
+fertile	O
+,	O
+and	O
+outwardly	O
+normal	O
+in	O
+appearance	O
+.	O
+
+One	O
+is	O
+to	O
+act	O
+within	O
+the	O
+visceral	O
+endoderm	O
+to	O
+promote	O
+proper	O
+streak	O
+morphogenesis	O
+.	O
+
+We	O
+propose	O
+that	O
+noi	B-GENE
+/	O
+pax2	B-GENE
+.	I-GENE
+1	I-GENE
+participates	O
+in	O
+sequential	O
+signaling	O
+processes	O
+as	O
+a	O
+key	O
+integrator	O
+of	O
+midbrain	O
+-	O
+hindbrain	O
+boundary	O
+development	O
+.	O
+
+METHODS	O
+:	O
+Fibrotic	O
+changes	O
+involving	O
+bone	O
+marrow	O
+were	O
+evaluated	O
+histologically	O
+semiquantitatively	O
+using	O
+reticulin	B-GENE
+fiber	O
+impregnation	O
+(	O
+method	O
+of	O
+Gomori	O
+)	O
+.	O
+
+We	O
+then	O
+studied	O
+four	O
+unrelated	O
+Japanese	O
+families	O
+with	O
+GSD	O
+-	O
+Ib	O
+,	O
+and	O
+found	O
+three	O
+novel	O
+mutations	O
+:	O
+a	O
+four	O
+-	O
+base	O
+deletion	O
+/	O
+two	O
+-	O
+base	O
+insertion	O
+,	O
+a	O
+point	O
+mutation	O
+within	O
+a	O
+consensus	O
+splicing	O
+donor	O
+site	O
+,	O
+and	O
+a	O
+missense	O
+mutation	O
+(	O
+W118R	O
+)	O
+.	O
+
+Removal	O
+of	O
+the	O
+carboxyl	O
+region	O
+severely	O
+reduced	O
+transcriptional	O
+activation	O
+.	O
+
+A	O
+"	O
+Level	O
+A	O
+"	O
+in	O
+vitro	O
+/	O
+in	O
+vivo	O
+correlation	O
+was	O
+established	O
+for	O
+a	O
+sustained	O
+release	O
+theophylline	O
+(	O
+CAS	O
+58	O
+-	O
+55	O
+-	O
+9	O
+)	O
+preparation	O
+(	O
+Bronchoretard	O
+)	O
+under	O
+investigation	O
+.	O
+
+METHOD	O
+:	O
+50	O
+consecutive	O
+children	O
+aged	O
+from	O
+6	O
+months	O
+to	O
+17	O
+years	O
+were	O
+included	O
+into	O
+the	O
+study	O
+which	O
+comprised	O
+questionnaires	O
+of	O
+patient	O
+and	O
+family	O
+histories	O
+,	O
+serological	O
+screening	O
+tests	O
+for	O
+common	O
+inhalational	O
+allergens	O
+(	O
+CAP	O
+SX1	O
+)	O
+,	O
+and	O
+determination	O
+of	O
+total	O
+serum	B-GENE
+immunoglobulin	I-GENE
+E	I-GENE
+(	O
+IgE	B-GENE
+)	O
+and	O
+of	O
+latex	O
+-	O
+specific	O
+serum	B-GENE
+IgE	I-GENE
+by	O
+solid	O
+-	O
+phase	O
+immunoassays	O
+.	O
+
+The	O
+PDE4A	B-GENE
+-	I-GENE
+subfamily	I-GENE
+-	I-GENE
+specific	I-GENE
+linker	I-GENE
+region	I-GENE
+LR1	O
+,	O
+which	O
+joins	O
+UCR1	O
+and	O
+UCR2	O
+,	O
+is	O
+encoded	O
+by	O
+two	O
+exons	O
+,	O
+whereas	O
+LR2	O
+,	O
+which	O
+joins	O
+UCR2	O
+to	O
+the	O
+catalytic	O
+unit	O
+,	O
+is	O
+encoded	O
+by	O
+a	O
+single	O
+exon	O
+.	O
+
+Pol32Delta	B-GENE
+strains	O
+are	O
+weak	O
+antimutators	O
+and	O
+are	O
+defective	O
+for	O
+damage	O
+-	O
+induced	O
+mutagenesis	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+,	O
+the	O
+results	O
+indicate	O
+that	O
+p53	B-GENE
+plays	O
+a	O
+defensive	O
+role	O
+against	O
+HBV	O
+by	O
+transcriptionally	O
+repressing	O
+the	O
+HBV	B-GENE
+core	I-GENE
+promoter	I-GENE
+through	O
+liver	B-GENE
+-	I-GENE
+specific	I-GENE
+enhancer	I-GENE
+II	I-GENE
+and	O
+HBx	B-GENE
+is	O
+required	O
+to	O
+counteract	O
+this	O
+inhibitory	O
+function	O
+of	O
+p53	B-GENE
+.	O
+
+To	O
+gain	O
+insight	O
+into	O
+the	O
+expression	O
+of	O
+the	O
+AtCP1	B-GENE
+gene	I-GENE
+,	O
+northern	O
+blot	O
+analysis	O
+was	O
+carried	O
+out	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+correlate	O
+the	O
+responsiveness	O
+to	O
+bronchoprovocation	O
+with	O
+methacholine	O
+in	O
+subjects	O
+a	O
+with	O
+allergic	O
+rhinitis	O
+during	O
+and	O
+out	O
+of	O
+the	O
+pollen	O
+season	O
+with	O
+total	O
+serum	O
+IgE	B-GENE
+and	O
+blood	O
+eosinophils	O
+.	O
+
+These	O
+results	O
+provide	O
+the	O
+first	O
+demonstration	O
+that	O
+an	O
+SR	B-GENE
+protein	I-GENE
+can	O
+influence	O
+splicing	O
+of	O
+specific	O
+pre	O
+-	O
+mRNAs	O
+in	O
+vivo	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+potential	O
+for	O
+prostate	O
+cancer	O
+chemoprevention	O
+using	O
+nonsteroidal	O
+anti	O
+-	O
+inflammatory	O
+drugs	O
+(	O
+cyclo	B-GENE
+-	I-GENE
+oxygenase	I-GENE
+inhibitors	O
+;	O
+NSAIDs	O
+)	O
+has	O
+received	O
+little	O
+attention	O
+.	O
+
+This	O
+study	O
+reports	O
+the	O
+isolation	O
+of	O
+a	O
+P	O
+.	O
+hybrida	O
+gene	O
+,	O
+jaf13	B-GENE
+,	O
+encoding	O
+a	O
+basic	B-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+protein	I-GENE
+that	O
+,	O
+on	O
+the	O
+basis	O
+of	O
+sequence	O
+homology	O
+and	O
+intron	O
+/	O
+exon	O
+structure	O
+,	O
+represents	O
+the	O
+P	O
+.	O
+hybrida	O
+orthologue	O
+of	O
+the	O
+Z	B-GENE
+.	I-GENE
+mays	I-GENE
+r	I-GENE
+genes	I-GENE
+.	O
+
+During	O
+the	O
+past	O
+4	O
+years	O
+,	O
+a	O
+purposeful	O
+search	O
+was	O
+made	O
+for	O
+electrocardiograms	O
+with	O
+documented	O
+reversible	O
+QRS	O
+changes	O
+associated	O
+with	O
+all	O
+acute	O
+injury	O
+pattern	O
+.	O
+
+Mutating	O
+a	O
+potential	O
+cleavage	O
+site	O
+located	O
+N	O
+-	O
+terminal	O
+to	O
+the	O
+protease	O
+domain	O
+,	O
+Gln2526	O
+-	O
+Asp2527	O
+,	O
+diminished	O
+processing	O
+.	O
+
+METHODS	O
+:	O
+Millipore	O
+ultrafiltration	O
+membranes	O
+of	O
+three	O
+different	O
+pore	O
+sizes	O
+were	O
+used	O
+as	O
+model	O
+lenticule	O
+materials	O
+.	O
+The	O
+nominal	O
+membrane	O
+pore	O
+sizes	O
+were	O
+0	O
+.	O
+1	O
+microm	O
+,	O
+0	O
+.	O
+45	O
+microm	O
+,	O
+and	O
+3	O
+microm	O
+;	O
+the	O
+surface	O
+roughness	O
+increased	O
+in	O
+the	O
+same	O
+order	O
+The	O
+membranes	O
+were	O
+coated	O
+with	O
+a	O
+thin	O
+layer	O
+of	O
+collagen	B-GENE
+I	I-GENE
+and	O
+implanted	O
+in	O
+a	O
+circular	O
+pocket	O
+of	O
+the	O
+anterior	O
+cornea	O
+of	O
+adult	O
+cats	O
+,	O
+and	O
+were	O
+clinically	O
+evaluated	O
+for	O
+the	O
+extent	O
+of	O
+epithelialization	O
+and	O
+the	O
+persistence	O
+of	O
+epithelial	O
+attachment	O
+.	O
+
+The	O
+role	O
+of	O
+calcitonin	B-GENE
+,	O
+and	O
+other	O
+agonists	O
+which	O
+activate	O
+the	O
+cAMP	O
+pathway	O
+,	O
+in	O
+regulating	O
+transcription	O
+of	O
+the	O
+human	B-GENE
+parathyroid	I-GENE
+hormone	I-GENE
+-	I-GENE
+related	I-GENE
+protein	I-GENE
+(	O
+PTHrP	B-GENE
+)	O
+gene	O
+was	O
+investigated	O
+in	O
+a	O
+human	O
+lung	O
+cancer	O
+cell	O
+line	O
+(	O
+BEN	O
+)	O
+.	O
+
+The	O
+combination	O
+of	O
+Pitx2	B-GENE
+and	O
+another	O
+homeodomain	B-GENE
+protein	I-GENE
+,	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+yielded	O
+a	O
+synergistic	O
+55	O
+-	O
+fold	O
+activation	O
+of	O
+the	O
+prolactin	B-GENE
+promoter	I-GENE
+in	O
+transfection	O
+assays	O
+.	O
+
+The	O
+biochemical	O
+and	O
+molecular	O
+spectrum	O
+of	O
+ornithine	B-GENE
+transcarbamylase	I-GENE
+deficiency	O
+.	O
+
+To	O
+further	O
+understand	O
+the	O
+role	O
+of	O
+cis	O
+-	O
+acting	O
+elements	O
+in	O
+these	O
+regulatory	O
+mechanisms	O
+,	O
+we	O
+have	O
+characterized	O
+a	O
+transcriptional	O
+promoter	O
+that	O
+drives	O
+germline	O
+expression	O
+of	O
+TCR	B-GENE
+beta	I-GENE
+gene	I-GENE
+segments	I-GENE
+in	O
+vivo	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+the	O
+crucial	O
+role	O
+of	O
+the	O
+mutations	O
+activating	O
+v	B-GENE
+-	I-GENE
+erbA	I-GENE
+as	O
+an	O
+oncogene	O
+is	O
+to	O
+'	O
+freeze	O
+'	O
+c	B-GENE
+-	I-GENE
+ErbA	I-GENE
+/	O
+TRalpha	B-GENE
+in	O
+its	O
+non	O
+-	O
+liganded	O
+,	O
+repressive	O
+conformation	O
+and	O
+to	O
+facilitate	O
+its	O
+overexpression	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+describe	O
+a	O
+mammalian	O
+cell	O
+-	O
+free	O
+transcription	O
+system	O
+reconstituted	O
+with	O
+only	O
+recombinant	O
+proteins	O
+and	O
+epitope	O
+-	O
+tagged	O
+multiprotein	O
+complexes	O
+.	O
+
+This	O
+repressor	O
+is	O
+however	O
+unlikely	O
+to	O
+mediate	O
+spi	B-GENE
+2	I-GENE
+.	I-GENE
+3	I-GENE
+3	I-GENE
+'	I-GENE
+UTR	I-GENE
+silencer	I-GENE
+action	O
+since	O
+it	O
+was	O
+not	O
+detected	O
+in	O
+rat	O
+hepatocytes	O
+.	O
+
+A	O
+prerequisite	O
+for	O
+the	O
+synthesis	O
+of	O
+sialylated	O
+glycoconjugates	O
+is	O
+the	O
+activated	O
+sugar	O
+-	O
+nucleotide	O
+cytidine	O
+5	O
+'	O
+-	O
+monophosphate	O
+N	O
+-	O
+acetylneuraminic	O
+acid	O
+(	O
+CMP	O
+-	O
+Neu5Ac	O
+)	O
+,	O
+which	O
+provides	O
+a	O
+substrate	O
+for	O
+Golgi	B-GENE
+sialyltransferases	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+bovine	B-GENE
+PEDF	I-GENE
+cDNA	I-GENE
+isolated	O
+here	O
+codes	O
+for	O
+a	O
+functional	O
+soluble	O
+secreted	B-GENE
+PEDF	I-GENE
+glycoprotein	I-GENE
+.	O
+
+We	O
+found	O
+sequences	O
+related	O
+to	O
+this	O
+insertion	O
+in	O
+wild	O
+-	O
+type	O
+strains	O
+of	O
+N	O
+.	O
+crassa	O
+and	O
+other	O
+Neurospora	O
+species	O
+.	O
+
+When	O
+cysteine	O
+is	O
+scanned	O
+through	O
+the	O
+helices	O
+,	O
+characteristic	O
+repeating	O
+patterns	O
+of	O
+solvent	O
+exposure	O
+and	O
+burial	O
+are	O
+observed	O
+.	O
+
+Human	B-GENE
+ULK1	I-GENE
+,	O
+a	O
+novel	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+related	O
+to	O
+UNC	B-GENE
+-	I-GENE
+51	I-GENE
+kinase	I-GENE
+of	O
+Caenorhabditis	O
+elegans	O
+:	O
+cDNA	O
+cloning	O
+,	O
+expression	O
+,	O
+and	O
+chromosomal	O
+assignment	O
+.	O
+
+Specifically	O
+,	O
+I	O
+use	O
+molecular	O
+markers	O
+that	O
+identify	O
+particular	O
+neuroectodermal	O
+domains	O
+,	O
+all	O
+neuroblasts	O
+or	O
+individual	O
+neuroblasts	O
+,	O
+to	O
+show	O
+that	O
+in	O
+DER	B-GENE
+mutant	I-GENE
+embryos	O
+(	O
+1	O
+)	O
+intermediate	O
+column	O
+neuroblasts	O
+do	O
+not	O
+form	O
+,	O
+(	O
+2	O
+)	O
+medial	O
+column	O
+neuroblasts	O
+often	O
+acquire	O
+identities	O
+inappropriate	O
+for	O
+their	O
+position	O
+,	O
+while	O
+(	O
+3	O
+)	O
+lateral	O
+neuroblasts	O
+develop	O
+normally	O
+.	O
+
+Cochlear	O
+microphonic	O
+potentials	O
+in	O
+patients	O
+with	O
+vestibular	O
+schwannomas	O
+.	O
+
+These	O
+results	O
+with	O
+clozapine	O
+illustrate	O
+that	O
+LI	O
+is	O
+sensitive	O
+to	O
+antipsychotics	O
+which	O
+differ	O
+in	O
+their	O
+mode	O
+of	O
+action	O
+and	O
+furthermore	O
+emphasize	O
+the	O
+value	O
+of	O
+LI	O
+as	O
+a	O
+test	O
+model	O
+for	O
+detecting	O
+the	O
+antipsychotic	O
+potential	O
+of	O
+novel	O
+drugs	O
+.	O
+
+The	O
+complement	B-GENE
+C3a	I-GENE
+anaphylatoxin	I-GENE
+receptor	I-GENE
+(	O
+C3aR	B-GENE
+)	O
+is	O
+a	O
+seven	B-GENE
+-	I-GENE
+transmembrane	I-GENE
+G	I-GENE
+-	I-GENE
+protein	I-GENE
+coupled	I-GENE
+chemoattractant	I-GENE
+receptor	I-GENE
+that	O
+on	O
+binding	O
+the	O
+C3a	B-GENE
+peptide	I-GENE
+ligand	I-GENE
+mediates	O
+numerous	O
+cellular	O
+responses	O
+,	O
+including	O
+histamine	O
+release	O
+from	O
+mast	O
+cells	O
+.	O
+smooth	O
+muscle	O
+contraction	O
+,	O
+and	O
+the	O
+directed	O
+migration	O
+of	O
+eosinophils	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Significant	O
+elevations	O
+of	O
+IL	B-GENE
+-	I-GENE
+1alpha	I-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+occur	O
+in	O
+patients	O
+with	O
+bacterial	O
+cystitis	O
+and	O
+microscopic	O
+hematuria	O
+.	O
+
+Band	O
+-	O
+shift	O
+assays	O
+were	O
+performed	O
+using	O
+the	O
+LPS	B-GENE
+-	I-GENE
+and	I-GENE
+IL	I-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+(	O
+LILRE	B-GENE
+)	O
+oligonucleotide	O
+,	O
+a	O
+gamma	B-GENE
+interferon	I-GENE
+activation	I-GENE
+site	I-GENE
+-	I-GENE
+like	I-GENE
+site	I-GENE
+that	O
+is	O
+present	O
+in	O
+the	O
+human	B-GENE
+IL	I-GENE
+-	I-GENE
+1beta	I-GENE
+promoter	I-GENE
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+region	O
+contains	O
+the	O
+PTP	B-GENE
+-	I-GENE
+like	I-GENE
+domain	I-GENE
+,	O
+whereas	O
+the	O
+N	O
+-	O
+terminal	O
+region	O
+shows	O
+no	O
+homology	O
+to	O
+any	O
+known	O
+mammalian	O
+protein	O
+.	O
+
+In	O
+addition	O
+,	O
+and	O
+in	O
+support	O
+of	O
+a	O
+mediating	O
+role	O
+of	O
+STATs	B-GENE
+in	O
+the	O
+activation	O
+of	O
+the	O
+p21	B-GENE
+promoter	I-GENE
+,	O
+overexpression	O
+of	O
+Stat3	B-GENE
+potentiated	O
+the	O
+cytokine	O
+effect	O
+on	O
+the	O
+p21	B-GENE
+promoter	I-GENE
+;	O
+whereas	O
+a	O
+dominant	B-GENE
+negative	I-GENE
+Stat3	I-GENE
+,	O
+or	O
+a	O
+mutation	O
+of	O
+the	O
+STAT	B-GENE
+response	I-GENE
+element	I-GENE
+on	O
+the	O
+promoter	O
+,	O
+significantly	O
+reduced	O
+the	O
+cytokine	O
+effect	O
+.	O
+
+The	O
+heterogeneous	O
+nuclear	B-GENE
+ribonucleoprotein	I-GENE
+C	I-GENE
+protein	I-GENE
+tetramer	I-GENE
+binds	O
+U1	B-GENE
+,	O
+U2	B-GENE
+,	O
+and	O
+U6	B-GENE
+snRNAs	I-GENE
+through	O
+its	O
+high	O
+affinity	O
+RNA	O
+binding	O
+domain	O
+(	O
+the	O
+bZIP	O
+-	O
+like	O
+motif	O
+)	O
+.	O
+
+On	O
+the	O
+comparison	O
+of	O
+correlated	O
+proportions	O
+for	O
+clustered	O
+data	O
+.	O
+
+A	O
+safe	O
+and	O
+simple	O
+system	O
+for	O
+the	O
+detection	O
+of	O
+sudden	O
+infant	O
+death	O
+syndrome	O
+(	O
+SIDS	O
+)	O
+is	O
+proposed	O
+.	O
+
+The	O
+resulting	O
+mutants	O
+were	O
+coexpressed	O
+with	O
+gE	B-GENE
+in	O
+the	O
+vaccinia	O
+virus	O
+-	O
+based	O
+vTF7	O
+-	O
+3	O
+system	O
+,	O
+and	O
+the	O
+formation	O
+and	O
+endoplasmic	O
+reticulum	O
+(	O
+ER	O
+)	O
+-	O
+to	O
+-	O
+Golgi	O
+transport	O
+of	O
+the	O
+hetero	O
+-	O
+oligomeric	O
+complex	O
+were	O
+monitored	O
+.	O
+
+Homozygous	O
+mutant	O
+mice	O
+,	O
+designated	O
+Cux	B-GENE
+/	O
+CDPDeltaCR1	B-GENE
+,	O
+display	O
+a	O
+phenotype	O
+characterized	O
+by	O
+curly	O
+vibrissae	O
+and	O
+wavy	O
+hair	O
+.	O
+
+The	O
+mutant	O
+protein	O
+is	O
+present	O
+at	O
+levels	O
+slightly	O
+greater	O
+than	O
+wild	O
+-	O
+type	O
+,	O
+but	O
+exhibits	O
+the	O
+same	O
+tissue	O
+distribution	O
+as	O
+wild	O
+-	O
+type	O
+protein	O
+,	O
+and	O
+has	O
+approximately	O
+normal	O
+affinity	O
+for	O
+known	O
+target	O
+sequences	O
+(	O
+though	O
+no	O
+DNA	O
+targets	O
+identified	O
+to	O
+date	O
+require	O
+the	O
+first	O
+cut	O
+repeat	O
+for	O
+binding	O
+)	O
+.	O
+
+METHODS	O
+:	O
+We	O
+retrospectively	O
+reviewed	O
+242	O
+adult	O
+cadaveric	O
+renal	O
+transplant	O
+recipients	O
+treated	O
+between	O
+11	O
+/	O
+91	O
+and	O
+5	O
+/	O
+97	O
+.	O
+
+The	O
+spectrum	O
+of	O
+age	O
+-	O
+associated	O
+brain	O
+abnormalities	O
+:	O
+their	O
+measurement	O
+and	O
+histopathological	O
+correlates	O
+.	O
+
+Our	O
+laboratory	O
+has	O
+recently	O
+identified	O
+two	O
+phosducin	B-GENE
+-	I-GENE
+like	I-GENE
+orphan	I-GENE
+proteins	I-GENE
+(	O
+PhLOP1	B-GENE
+and	O
+PhLOP2	B-GENE
+)	O
+that	O
+lack	O
+the	O
+ability	O
+to	O
+interact	O
+with	O
+Gbetagamma	B-GENE
+.	O
+
+Reverse	B-GENE
+transcriptase	I-GENE
+-	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+RT	B-GENE
+-	O
+PCR	O
+)	O
+was	O
+performed	O
+using	O
+eyestalk	O
+complementary	O
+DNA	O
+of	O
+the	O
+sand	O
+shrimp	O
+Metapenaeus	O
+ensis	O
+.	O
+
+In	O
+contrast	O
+,	O
+transcription	O
+initiating	O
+from	O
+opuE	B-GENE
+P	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+sigma	B-GENE
+A	I-GENE
+)	O
+rose	O
+in	O
+proportion	O
+to	O
+the	O
+external	O
+osmolarity	O
+and	O
+was	O
+maintained	O
+at	O
+high	O
+levels	O
+.	O
+
+Randomly	O
+selected	O
+300	O
+children	O
+aged	O
+3	O
+months	O
+-	O
+3	O
+yr	O
+were	O
+analysed	O
+over	O
+a	O
+period	O
+of	O
+one	O
+year	O
+for	O
+estimating	O
+prevalence	O
+of	O
+nutritional	O
+anaemia	O
+.	O
+
+In	O
+insects	O
+,	O
+arylalkylamine	B-GENE
+N	I-GENE
+-	I-GENE
+acetyltransferases	I-GENE
+(	O
+AANATs	B-GENE
+)	O
+have	O
+been	O
+implicated	O
+in	O
+several	O
+physiological	O
+processes	O
+,	O
+including	O
+sclerotization	O
+,	O
+inactivation	O
+of	O
+certain	O
+neurotransmitters	O
+,	O
+and	O
+,	O
+similar	O
+to	O
+the	O
+function	O
+in	O
+vertebrates	O
+,	O
+catalysis	O
+of	O
+the	O
+rate	O
+-	O
+limiting	O
+step	O
+in	O
+melatonin	O
+biosynthesis	O
+.	O
+
+These	O
+results	O
+establish	O
+that	O
+hydroquinones	O
+lead	O
+to	O
+mutagenicity	O
+and	O
+carcinogenicity	O
+.	O
+
+IA	O
+-	O
+CT	O
+with	O
+cisplatin	O
+50	O
+mg	O
+and	O
+doxorubicin	O
+30	O
+mg	O
+was	O
+administered	O
+by	O
+one	O
+shot	O
+method	O
+in	O
+bilateral	O
+internal	O
+iliac	O
+arteries	O
+.	O
+
+Arnt3	B-GENE
+mRNA	I-GENE
+was	O
+expressed	O
+in	O
+brain	O
+,	O
+skeletal	O
+muscle	O
+,	O
+13	O
+.	O
+5	O
+-	O
+day	O
+embryos	O
+,	O
+and	O
+P19	O
+cells	O
+treated	O
+with	O
+retinoic	O
+acid	O
+.	O
+
+The	O
+genomic	O
+structure	O
+and	O
+chromosomal	O
+location	O
+of	O
+the	O
+human	B-GENE
+TR2	I-GENE
+orphan	I-GENE
+receptor	I-GENE
+,	O
+a	O
+member	O
+of	O
+the	O
+steroid	B-GENE
+receptor	I-GENE
+superfamily	I-GENE
+.	O
+
+Correlation	O
+of	O
+skin	O
+disorders	O
+with	O
+CD4	B-GENE
+lymphocyte	O
+counts	O
+in	O
+patients	O
+with	O
+HIV	O
+/	O
+AIDS	O
+.	O
+
+E2F	B-GENE
+-	I-GENE
+6	I-GENE
+shares	O
+significant	O
+homology	O
+with	O
+E2Fs	B-GENE
+1	I-GENE
+-	I-GENE
+5	I-GENE
+,	O
+especially	O
+within	O
+the	O
+DNA	O
+binding	O
+,	O
+heterodimerization	O
+and	O
+marked	O
+box	O
+domains	O
+.	O
+
+The	O
+IE13	O
+.	O
+1	O
+cell	O
+line	O
+was	O
+able	O
+to	O
+complement	O
+a	O
+recombinant	O
+virus	O
+in	O
+which	O
+both	O
+copies	O
+of	O
+the	O
+IE	B-GENE
+gene	I-GENE
+were	O
+replaced	O
+by	O
+insertion	O
+of	O
+the	O
+Escherichia	B-GENE
+coli	I-GENE
+lacZ	I-GENE
+gene	I-GENE
+.	O
+
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+analyses	O
+revealed	O
+two	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+HNF1	B-GENE
+)	O
+,	O
+three	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+)	O
+,	O
+and	O
+one	O
+consensus	O
+palindromic	O
+thyroid	O
+hormone	O
+response	O
+elements	O
+within	O
+the	O
+first	O
+215	O
+base	O
+pairs	O
+(	O
+bp	O
+)	O
+of	O
+the	O
+promoter	O
+sequence	O
+of	O
+rat	B-GENE
+Std	I-GENE
+.	O
+
+Thus	O
+,	O
+these	O
+studies	O
+on	O
+rat	B-GENE
+Std	I-GENE
+promoter	I-GENE
+function	O
+indicate	O
+that	O
+(	O
+i	O
+)	O
+HNF1	B-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+are	O
+responsible	O
+for	O
+liver	O
+specificity	O
+of	O
+the	O
+rat	B-GENE
+Std	I-GENE
+gene	I-GENE
+;	O
+(	O
+ii	O
+)	O
+androgenic	O
+repression	O
+of	O
+the	O
+gene	O
+requires	O
+the	O
+presence	O
+of	O
+all	O
+of	O
+the	O
+OCT	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+elements	I-GENE
+between	O
+positions	O
+-	O
+231	O
+and	O
+-	O
+292	O
+;	O
+and	O
+(	O
+iii	O
+)	O
+AR	B-GENE
+may	O
+exert	O
+its	O
+negative	O
+regulatory	O
+effect	O
+indirectly	O
+through	O
+transcriptional	O
+interference	O
+of	O
+OCT	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+rather	O
+than	O
+through	O
+a	O
+direct	O
+DNA	B-GENE
+-	I-GENE
+AR	I-GENE
+interaction	O
+.	O
+
+Purified	O
+Hsk1	B-GENE
+phosphorylates	O
+the	O
+Cdc19	B-GENE
+(	O
+Mcm2	B-GENE
+)	O
+subunit	O
+of	O
+the	O
+six	B-GENE
+-	I-GENE
+member	I-GENE
+minichromosome	I-GENE
+maintenance	I-GENE
+protein	I-GENE
+complex	I-GENE
+purified	O
+from	O
+fission	O
+yeast	O
+.	O
+
+The	O
+yeast	B-GENE
+MMS2	I-GENE
+gene	I-GENE
+was	O
+cloned	O
+by	O
+its	O
+ability	O
+to	O
+complement	O
+the	O
+methyl	O
+methanesulfonate	O
+sensitivity	O
+of	O
+the	O
+mms2	B-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+and	O
+was	O
+later	O
+shown	O
+to	O
+be	O
+involved	O
+in	O
+DNA	O
+post	O
+-	O
+replication	O
+repair	O
+.	O
+
+Expression	O
+of	O
+the	O
+human	B-GENE
+papillomavirus	I-GENE
+type	I-GENE
+11	I-GENE
+E5A	I-GENE
+protein	I-GENE
+from	O
+the	O
+E1E4	B-GENE
+,	I-GENE
+E5	I-GENE
+transcript	I-GENE
+.	O
+
+Anesthesia	O
+with	O
+M	O
+/	O
+K	O
+was	O
+reversed	O
+after	O
+41	O
+.	O
+6	O
+min	O
+of	O
+immobilization	O
+with	O
+atipamezole	O
+.	O
+
+There	O
+was	O
+no	O
+evident	O
+inciting	O
+agent	O
+of	O
+the	O
+disease	O
+.	O
+
+MK	O
+-	O
+801	O
+administration	O
+resulted	O
+in	O
+a	O
+biphasic	O
+response	O
+in	O
+seizure	O
+latency	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+distribution	O
+of	O
+endocytic	O
+markers	O
+is	O
+not	O
+affected	O
+.	O
+
+Toxicity	O
+during	O
+the	O
+therapeutic	O
+period	O
+was	O
+not	O
+significant	O
+in	O
+the	O
+study	O
+group	O
+compared	O
+with	O
+the	O
+historical	O
+control	O
+,	O
+treated	O
+with	O
+the	O
+same	O
+regimen	O
+without	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+.	O
+
+Both	O
+methods	O
+were	O
+employed	O
+for	O
+various	O
+focal	O
+-	O
+film	O
+distances	O
+,	O
+image	O
+intensifier	O
+tube	O
+modes	O
+and	O
+laser	O
+printer	O
+formats	O
+.	O
+
+The	O
+effect	O
+of	O
+Rho	B-GENE
+on	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+independent	O
+of	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+pathway	O
+,	O
+as	O
+a	O
+dominant	B-GENE
+-	I-GENE
+negative	I-GENE
+MEK	I-GENE
+and	O
+a	O
+MEK	B-GENE
+inhibitor	O
+(	O
+PD98059	O
+)	O
+did	O
+not	O
+affect	O
+Rho	B-GENE
+-	O
+induced	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+of	O
+residues	O
+in	O
+this	O
+domain	O
+(	O
+R82A	O
+,	O
+K85A	O
+,	O
+K88A	O
+,	O
+and	O
+V89A	O
+)	O
+resulted	O
+in	O
+proteins	O
+which	O
+failed	O
+to	O
+transactivate	O
+from	O
+the	O
+HTLV	B-GENE
+-	I-GENE
+1	I-GENE
+LTR	I-GENE
+in	O
+vivo	O
+.	O
+
+Mutations	O
+within	O
+the	O
+C	O
+terminus	O
+of	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+at	O
+serine	O
+residues	O
+that	O
+are	O
+phosphorylation	O
+targets	O
+for	O
+growth	O
+factors	O
+and	O
+MAP	B-GENE
+kinase	I-GENE
+completely	O
+abrogate	O
+transactivation	O
+and	O
+block	O
+potentiation	O
+by	O
+MAP	B-GENE
+kinase	I-GENE
+.	O
+
+In	O
+the	O
+former	O
+cells	O
+,	O
+ets	B-GENE
+-	I-GENE
+2	I-GENE
+was	O
+a	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+immediate	O
+-	O
+early	O
+response	O
+gene	O
+,	O
+and	O
+phosphorylated	O
+ets	B-GENE
+-	I-GENE
+2	I-GENE
+was	O
+detected	O
+after	O
+2	O
+to	O
+4	O
+h	O
+,	O
+coincident	O
+with	O
+expression	O
+of	O
+ets	B-GENE
+-	I-GENE
+2	I-GENE
+protein	I-GENE
+.	O
+
+Persistent	O
+activation	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinases	I-GENE
+p42	I-GENE
+and	O
+p44	B-GENE
+and	O
+ets	B-GENE
+-	I-GENE
+2	I-GENE
+phosphorylation	O
+in	O
+response	O
+to	O
+colony	B-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+1	I-GENE
+/	O
+c	B-GENE
+-	I-GENE
+fms	I-GENE
+signaling	O
+.	O
+
+Identification	O
+of	O
+a	O
+proline	O
+-	O
+rich	O
+sequence	O
+in	O
+the	O
+CD2	B-GENE
+cytoplasmic	I-GENE
+domain	I-GENE
+critical	O
+for	O
+regulation	O
+of	O
+integrin	B-GENE
+-	O
+mediated	O
+adhesion	O
+and	O
+activation	O
+of	O
+phosphoinositide	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+.	O
+
+Vam7p	B-GENE
+,	O
+a	O
+SNAP	B-GENE
+-	I-GENE
+25	I-GENE
+-	I-GENE
+like	I-GENE
+molecule	I-GENE
+,	O
+and	O
+Vam3p	B-GENE
+,	O
+a	O
+syntaxin	B-GENE
+homolog	I-GENE
+,	O
+function	O
+together	O
+in	O
+yeast	O
+vacuolar	O
+protein	O
+trafficking	O
+.	O
+
+We	O
+have	O
+tested	O
+this	O
+possibility	O
+by	O
+constructing	O
+a	O
+consecutive	O
+series	O
+of	O
+cysteine	O
+substitutions	O
+in	O
+the	O
+Neu	B-GENE
+juxtamembrane	I-GENE
+domain	I-GENE
+in	O
+order	O
+to	O
+force	O
+dimerization	O
+along	O
+a	O
+series	O
+of	O
+interreceptor	O
+faces	O
+.	O
+
+It	O
+has	O
+been	O
+demonstrated	O
+previously	O
+that	O
+Pax	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+a	O
+paired	B-GENE
+domain	I-GENE
+(	O
+PD	B-GENE
+)	O
+/	O
+homeodomain	B-GENE
+(	O
+HD	B-GENE
+)	O
+transcription	O
+factor	O
+critical	O
+for	O
+eye	O
+development	O
+,	O
+contributes	O
+to	O
+the	O
+activation	O
+of	O
+the	O
+alphaB	B-GENE
+-	I-GENE
+,	I-GENE
+alphaA	I-GENE
+-	I-GENE
+,	I-GENE
+delta1	I-GENE
+-	I-GENE
+,	I-GENE
+and	I-GENE
+zeta	I-GENE
+-	I-GENE
+crystallin	I-GENE
+genes	O
+in	O
+the	O
+lens	O
+.	O
+
+Tctex	B-GENE
+-	I-GENE
+1	I-GENE
+binding	O
+required	O
+the	O
+first	O
+19	O
+amino	O
+acids	O
+of	O
+Fyn	B-GENE
+and	O
+integrity	O
+of	O
+two	O
+lysine	O
+residues	O
+within	O
+this	O
+sequence	O
+that	O
+were	O
+previously	O
+shown	O
+to	O
+be	O
+important	O
+for	O
+Fyn	B-GENE
+interactions	O
+with	O
+the	O
+immunoreceptor	O
+tyrosine	O
+-	O
+based	O
+activation	O
+motifs	O
+(	O
+ITAMs	O
+)	O
+of	O
+lymphocyte	B-GENE
+Ag	I-GENE
+receptors	I-GENE
+.	O
+
+The	O
+prothrombin	B-GENE
+gene	I-GENE
+G20210A	I-GENE
+mutation	I-GENE
+is	O
+not	O
+found	O
+among	O
+Japanese	O
+patients	O
+with	O
+deep	O
+vein	O
+thrombosis	O
+and	O
+healthy	O
+individuals	O
+.	O
+
+In	O
+the	O
+studies	O
+described	O
+in	O
+this	O
+report	O
+,	O
+we	O
+have	O
+investigated	O
+the	O
+signaling	O
+pathway	O
+(	O
+s	O
+)	O
+that	O
+are	O
+responsible	O
+for	O
+CREB	B-GENE
+activation	O
+in	O
+normal	O
+T	O
+cells	O
+.	O
+
+Respondents	O
+who	O
+lived	O
+with	O
+a	O
+spouse	O
+/	O
+partner	O
+only	O
+were	O
+less	O
+likely	O
+to	O
+have	O
+an	O
+unfavorable	O
+BMI	O
+status	O
+than	O
+people	O
+in	O
+the	O
+other	O
+two	O
+groups	O
+.	O
+
+Isolation	O
+of	O
+a	O
+novel	O
+TP53	B-GENE
+target	I-GENE
+gene	I-GENE
+from	O
+a	O
+colon	O
+cancer	O
+cell	O
+line	O
+carrying	O
+a	O
+highly	O
+regulated	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+TP53	I-GENE
+expression	O
+system	O
+.	O
+
+Overexpression	O
+of	O
+MDR1	B-GENE
+has	O
+been	O
+demonstrated	O
+in	O
+many	O
+cancers	O
+,	O
+both	O
+in	O
+patient	O
+tumors	O
+and	O
+in	O
+cell	O
+lines	O
+selected	O
+with	O
+a	O
+variety	O
+of	O
+chemotherapeutic	O
+agents	O
+.	O
+
+Cytogenetic	O
+and	O
+molecular	O
+characterization	O
+of	O
+random	O
+chromosomal	O
+rearrangements	O
+activating	O
+the	O
+drug	O
+resistance	O
+gene	O
+,	O
+MDR1	B-GENE
+/	O
+P	B-GENE
+-	I-GENE
+glycoprotein	I-GENE
+,	O
+in	O
+drug	O
+-	O
+selected	O
+cell	O
+lines	O
+and	O
+patients	O
+with	O
+drug	O
+refractory	O
+ALL	O
+.	O
+
+BACKGROUND	O
+:	O
+It	O
+is	O
+generally	O
+accepted	O
+that	O
+smoking	O
+increases	O
+blood	O
+pressure	O
+and	O
+inhibits	O
+muscle	O
+sympathetic	O
+nerve	O
+activity	O
+(	O
+SNA	O
+)	O
+.	O
+
+When	O
+the	O
+blood	O
+pressure	O
+increase	O
+in	O
+response	O
+to	O
+smoking	O
+was	O
+blunted	O
+by	O
+nitroprusside	O
+infusion	O
+,	O
+there	O
+was	O
+a	O
+striking	O
+increase	O
+in	O
+muscle	O
+SNA	O
+.	O
+
+After	O
+that	O
+report	O
+,	O
+carboxypeptidase	B-GENE
+D	I-GENE
+(	O
+CPD	B-GENE
+)	O
+was	O
+subsequently	O
+purified	O
+from	O
+bovine	O
+pituitary	O
+and	O
+characterized	O
+as	O
+a	O
+novel	O
+carboxypeptidase	B-GENE
+E	I-GENE
+(	O
+CPE	B-GENE
+)	O
+-	O
+like	O
+enzyme	O
+,	O
+with	O
+many	O
+characteristics	O
+in	O
+common	O
+with	O
+duck	O
+gp180	B-GENE
+(	O
+Song	O
+,	O
+L	O
+.	O
+,	O
+Fricker	O
+,	O
+L	O
+.	O
+D	O
+.	O
+,	O
+1995	O
+.	O
+
+RA	O
+-	O
+treatment	O
+of	O
+these	O
+transfectants	O
+induced	O
+morphologic	O
+and	O
+immunophenotypic	O
+maturation	O
+,	O
+changes	O
+in	O
+RA	O
+-	O
+regulated	O
+genes	O
+,	O
+and	O
+a	O
+G1	O
+cell	O
+cycle	O
+arrest	O
+in	O
+a	O
+manner	O
+similar	O
+to	O
+parental	O
+NT2	O
+/	O
+D1	O
+cells	O
+.	O
+
+The	O
+histopathology	O
+and	O
+neovascularization	O
+did	O
+not	O
+appreciably	O
+differ	O
+between	O
+xenograft	O
+tumors	O
+derived	O
+from	O
+FGF4	B-GENE
+over	O
+-	O
+expressing	O
+versus	O
+control	O
+transfectants	O
+.	O
+
+For	O
+smaller	O
+vessels	O
+up	O
+to	O
+a	O
+diameter	O
+of	O
+0	O
+.	O
+5	O
+mm	O
+,	O
+treatments	O
+at	O
+16	O
+and	O
+18	O
+J	O
+/	O
+cm2	O
+showed	O
+good	O
+results	O
+in	O
+60	O
+and	O
+82	O
+%	O
+respectively	O
+;	O
+for	O
+vessels	O
+up	O
+to	O
+1	O
+mm	O
+in	O
+27	O
+and	O
+33	O
+%	O
+.	O
+
+RXR	B-GENE
+-	I-GENE
+gamma	I-GENE
+expression	O
+produced	O
+significant	O
+reduction	O
+in	O
+levels	O
+of	O
+RA	O
+-	O
+responsive	O
+genes	O
+including	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+inhibitors	O
+p21Cip1	B-GENE
+/	O
+WAF1	B-GENE
+and	O
+p27Kip1	B-GENE
+,	O
+resulting	O
+in	O
+increased	O
+cdc2	B-GENE
+and	O
+cdk2	B-GENE
+kinase	I-GENE
+activity	O
+and	O
+RB	B-GENE
+phosphorylation	O
+.	O
+
+Generally	O
+ILC	O
+and	O
+ILVF	O
+values	O
+decreased	O
+with	O
+increasing	O
+exposure	O
+time	O
+with	O
+rate	O
+constants	O
+ranging	O
+from	O
+0	O
+.	O
+03	O
+to	O
+0	O
+.	O
+33	O
+day	O
+-	O
+1	O
+(	O
+wet	O
+and	O
+lipid	O
+weight	O
+)	O
+for	O
+ILC	O
+and	O
+0	O
+.	O
+03	O
+to	O
+0	O
+.	O
+31	O
+day	O
+-	O
+1	O
+for	O
+ILVF	O
+.	O
+
+These	O
+sequence	O
+analyses	O
+suggest	O
+that	O
+xIRS	B-GENE
+-	I-GENE
+u	I-GENE
+is	O
+a	O
+novel	O
+member	O
+of	O
+the	O
+IRS	B-GENE
+family	I-GENE
+rather	O
+than	O
+a	O
+Xenopus	O
+homolog	O
+of	O
+an	O
+existing	O
+member	O
+.	O
+
+The	O
+present	O
+study	O
+sought	O
+to	O
+develop	O
+an	O
+equation	O
+to	O
+estimate	O
+VO2peak	O
+in	O
+peripheral	O
+arterial	O
+occlusive	O
+disease	O
+(	O
+PAOD	O
+)	O
+patients	O
+with	O
+intermittent	O
+claudication	O
+and	O
+to	O
+determine	O
+independent	O
+predictors	O
+of	O
+VO2peak	O
+in	O
+this	O
+population	O
+.	O
+
+The	O
+Abbreviated	O
+Injury	O
+Scale	O
+(	O
+AIS	O
+)	O
+,	O
+Injury	O
+Severity	O
+Scale	O
+and	O
+TRISS	O
+methodology	O
+comprise	O
+a	O
+mathematically	O
+sound	O
+system	O
+for	O
+the	O
+analysis	O
+of	O
+injuries	O
+and	O
+injured	O
+patients	O
+.	O
+
+This	O
+hypothesis	O
+was	O
+tested	O
+by	O
+introducing	O
+mutations	O
+at	O
+each	O
+of	O
+the	O
+three	O
+histidine	O
+pairs	O
+,	O
+the	O
+H382	O
+-	O
+X2	O
+-	O
+H385	O
+pair	O
+,	O
+the	O
+H411	O
+-	O
+X2	O
+-	O
+H414	O
+pair	O
+and	O
+the	O
+H430	O
+-	O
+X5	O
+-	O
+H436	O
+pair	O
+,	O
+which	O
+constitute	O
+the	O
+histidine	O
+-	O
+rich	O
+region	O
+near	O
+the	O
+C	O
+terminus	O
+of	O
+gp17	B-GENE
+.	O
+
+Using	O
+backcross	O
+analysis	O
+,	O
+both	O
+exons	O
+1	O
+and	O
+4	O
+mapped	O
+to	O
+a	O
+proximal	O
+region	O
+of	O
+murine	O
+Chromosome	O
+4	O
+indistinguishable	O
+from	O
+the	O
+vacillans	B-GENE
+gene	I-GENE
+.	O
+
+Seventy	O
+-	O
+five	O
+percent	O
+of	O
+children	O
+who	O
+received	O
+a	O
+second	O
+transplant	O
+for	O
+HCV	O
+hepatitis	O
+had	O
+early	O
+histologic	O
+recurrence	O
+that	O
+led	O
+to	O
+liver	O
+failure	O
+and	O
+death	O
+.	O
+
+However	O
+,	O
+both	O
+TPN	O
+groups	O
+showed	O
+a	O
+marked	O
+increase	O
+in	O
+activities	O
+of	O
+liver	O
+lysosomal	B-GENE
+enzymes	I-GENE
+.	O
+
+Regulation	O
+of	O
+embryonic	O
+growth	O
+and	O
+lysosomal	O
+targeting	O
+by	O
+the	O
+imprinted	O
+Igf2	B-GENE
+/	O
+Mpr	B-GENE
+gene	O
+.	O
+
+Furthermore	O
+,	O
+early	O
+-	O
+and	O
+late	O
+-	O
+firing	O
+origins	O
+differ	O
+not	O
+in	O
+the	O
+timing	O
+of	O
+their	O
+recruitment	O
+of	O
+an	O
+Mcm	B-GENE
+protein	I-GENE
+,	O
+but	O
+in	O
+the	O
+timing	O
+of	O
+RPA	B-GENE
+'	I-GENE
+s	I-GENE
+recruitment	O
+.	O
+
+Thus	O
+,	O
+in	O
+the	O
+presence	O
+of	O
+active	B-GENE
+S	I-GENE
+-	I-GENE
+CDKs	I-GENE
+and	O
+Dbf4	B-GENE
+/	O
+Cdc7	B-GENE
+,	O
+Mcms	B-GENE
+may	O
+open	O
+origins	O
+and	O
+thereby	O
+facilitate	O
+the	O
+loading	O
+of	O
+RPA	B-GENE
+.	O
+
+Tyrosine	O
+phosphorylated	O
+STATs	B-GENE
+dimerize	O
+and	O
+translocate	O
+into	O
+the	O
+nucleus	O
+to	O
+activate	O
+specific	O
+genes	O
+.	O
+
+Nonsynonymous	O
+substitution	O
+in	O
+abalone	O
+sperm	O
+fertilization	O
+genes	O
+exceeds	O
+substitution	O
+in	O
+introns	O
+and	O
+mitochondrial	O
+DNA	O
+.	O
+
+Gel	O
+retardation	O
+assays	O
+detected	O
+ZiaR	B-GENE
+-	O
+dependent	O
+complexes	O
+forming	O
+with	O
+the	O
+zia	B-GENE
+operator	I-GENE
+-	I-GENE
+promoter	I-GENE
+and	O
+ZiaR	B-GENE
+-	O
+DNA	O
+binding	O
+was	O
+enhanced	O
+by	O
+treatment	O
+with	O
+a	O
+metal	O
+-	O
+chelator	O
+in	O
+vitro	O
+.	O
+
+CONCLUSION	O
+:	O
+Although	O
+quantitative	O
+and	O
+qualitative	O
+criteria	O
+for	O
+diagnosing	O
+fatty	O
+liver	O
+on	O
+helical	O
+CT	O
+can	O
+be	O
+determined	O
+,	O
+they	O
+are	O
+protocol	O
+-	O
+specific	O
+.	O
+
+The	O
+PC	O
+-	O
+based	O
+RTPS	O
+is	O
+designed	O
+to	O
+run	O
+in	O
+the	O
+Microsoft	O
+Windows	O
+3	O
+.	O
+11	O
+environment	O
+(	O
+and	O
+later	O
+versions	O
+)	O
+,	O
+for	O
+computers	O
+equipped	O
+with	O
+486	O
+or	O
+Pentium	O
+processors	O
+.	O
+
+Alternatively	O
+,	O
+the	O
+similarity	O
+in	O
+apparent	O
+regulatory	O
+action	O
+of	O
+the	O
+genes	O
+may	O
+indicate	O
+allelic	O
+differences	O
+wherein	O
+the	O
+IS1112C	B-GENE
+Rf3	B-GENE
+allele	I-GENE
+may	O
+differ	O
+from	O
+alleles	O
+of	O
+maintainer	O
+lines	O
+by	O
+the	O
+capability	O
+to	O
+regulate	O
+both	O
+orf107	B-GENE
+and	O
+urf209	B-GENE
+processing	O
+activities	O
+.	O
+
+JCAHO	O
+revised	O
+interpretation	O
+
+A	O
+human	O
+SPT3	B-GENE
+-	O
+TAFII31	B-GENE
+-	O
+GCN5	B-GENE
+-	O
+L	B-GENE
+acetylase	I-GENE
+complex	O
+distinct	O
+from	O
+transcription	B-GENE
+factor	I-GENE
+IID	I-GENE
+.	O
+
+Oleate	O
+induced	O
+steady	O
+-	O
+state	O
+levels	O
+of	O
+M	B-GENE
+-	I-GENE
+CPT	I-GENE
+I	I-GENE
+mRNA	I-GENE
+4	O
+.	O
+5	O
+-	O
+fold	O
+.	O
+
+Mapping	O
+of	O
+the	O
+DNA	O
+binding	O
+domain	O
+of	O
+the	O
+copper	O
+-	O
+responsive	O
+transcription	O
+factor	O
+Mac1	B-GENE
+from	I-GENE
+Saccharomyces	I-GENE
+cerevisiae	I-GENE
+.	O
+
+A	O
+further	O
+mechanism	O
+increasing	O
+specific	O
+activation	O
+was	O
+cooperation	O
+of	O
+receptors	O
+at	O
+multiple	O
+and	O
+weak	O
+HREs	O
+,	O
+which	O
+was	O
+accentuated	O
+in	O
+the	O
+presence	O
+of	O
+both	O
+the	O
+AR	B-GENE
+N	O
+terminus	O
+and	O
+ligand	O
+binding	O
+domain	O
+.	O
+
+Previously	O
+,	O
+we	O
+characterized	O
+a	O
+DNA	O
+-	O
+binding	O
+protein	O
+,	O
+HS2NF5	B-GENE
+,	O
+that	O
+bound	O
+tightly	O
+to	O
+a	O
+conserved	O
+region	O
+within	O
+hypersensitive	O
+site	O
+2	O
+(	O
+HS2	O
+)	O
+of	O
+the	O
+human	B-GENE
+beta	I-GENE
+-	I-GENE
+globin	I-GENE
+locus	I-GENE
+control	I-GENE
+region	I-GENE
+(	O
+LCR	O
+)	O
+(	O
+Lam	O
+,	O
+L	O
+.	O
+
+The	O
+CBF1	B-GENE
+site	I-GENE
+within	O
+HS2	O
+resides	O
+near	O
+sites	O
+for	O
+hematopoietic	O
+regulators	O
+such	O
+as	O
+GATA	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+NF	B-GENE
+-	I-GENE
+E2	I-GENE
+,	O
+and	O
+TAL1	B-GENE
+.	O
+
+The	O
+rat	B-GENE
+branched	I-GENE
+-	I-GENE
+chain	I-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+oxo	I-GENE
+-	I-GENE
+acid	I-GENE
+dehydrogenase	I-GENE
+(	I-GENE
+BCOD	I-GENE
+)	I-GENE
+kinase	I-GENE
+mRNA	I-GENE
+is	O
+transcribed	O
+from	O
+a	O
+TATA	O
+-	O
+less	O
+promoter	O
+that	O
+has	O
+GC	O
+-	O
+rich	O
+sequences	O
+and	O
+two	O
+putative	O
+Sp1	B-GENE
+binding	I-GENE
+sites	I-GENE
+near	O
+the	O
+transcription	O
+start	O
+site	O
+.	O
+
+Co	O
+-	O
+transfection	O
+of	O
+the	O
+Sp1	B-GENE
+expression	O
+plasmid	O
+and	O
+the	O
+-	O
+58	O
+promoter	O
+construct	O
+into	O
+Drosophila	O
+Schneider	O
+cells	O
+revealed	O
+that	O
+Sp1	B-GENE
+contributed	O
+to	O
+the	O
+kinase	O
+basal	O
+promoter	O
+activity	O
+by	O
+binding	O
+to	O
+the	O
+non	O
+-	O
+consensus	O
+site	O
+in	O
+the	O
+-	O
+58	O
+region	O
+.	O
+
+Until	O
+such	O
+investigations	O
+are	O
+performed	O
+,	O
+we	O
+conclude	O
+that	O
+the	O
+role	O
+for	O
+adjuvant	O
+treatment	O
+is	O
+questionable	O
+and	O
+that	O
+TME	O
+surgery	O
+is	O
+preferred	O
+as	O
+the	O
+treatment	O
+option	O
+for	O
+Stage	O
+T1	O
+-	O
+T3	O
+rectal	O
+cancers	O
+.	O
+
+Likewise	O
+,	O
+at	O
+150	O
+degrees	O
+C	O
+with	O
+2	O
+%	O
+APS	O
+the	O
+surface	O
+density	O
+of	O
+NH2	O
+groups	O
+reached	O
+a	O
+maximum	O
+at	O
+24	O
+hr	O
+and	O
+remained	O
+relatively	O
+constant	O
+up	O
+to	O
+96	O
+hr	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+results	O
+suggest	O
+that	O
+the	O
+cooperation	O
+of	O
+transcription	B-GENE
+factors	I-GENE
+NF	I-GENE
+-	I-GENE
+kappaB	I-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+essential	O
+for	O
+transactivation	O
+of	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+gene	I-GENE
+by	O
+HTLV	B-GENE
+-	I-GENE
+I	I-GENE
+Tax	I-GENE
+.	O
+
+This	O
+study	O
+examines	O
+the	O
+cooperative	O
+effects	O
+of	O
+a	O
+human	O
+estrogen	B-GENE
+receptor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+ERalpha	B-GENE
+)	O
+isoform	O
+on	O
+estrogen	O
+(	O
+E2	O
+)	O
+-	O
+mediated	O
+gene	O
+activation	O
+in	O
+U2	O
+-	O
+OS	O
+osteosarcoma	O
+cells	O
+.	O
+
+Transfection	O
+of	O
+increasing	O
+amounts	O
+of	O
+delta5ERalpha	B-GENE
+expression	O
+vector	O
+into	O
+[	O
+ERalpha	B-GENE
++	O
+]	O
+OS	O
+cells	O
+resulted	O
+in	O
+potentiation	O
+of	O
+E2	O
+-	O
+stimulated	O
+ERELuc	B-GENE
+activity	O
+in	O
+a	O
+synergistic	O
+,	O
+dose	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Studies	O
+using	O
+the	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+also	O
+did	O
+not	O
+provide	O
+evidence	O
+for	O
+the	O
+formation	O
+of	O
+a	O
+VDR	B-GENE
+-	O
+TR	B-GENE
+protein	O
+-	O
+protein	O
+interaction	O
+.	O
+
+We	O
+did	O
+not	O
+observe	O
+any	O
+changes	O
+in	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+or	O
+Bcl	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+(	O
+Bcl	B-GENE
+-	I-GENE
+x	I-GENE
+,	O
+Bax	B-GENE
+,	O
+and	O
+Bad	B-GENE
+)	O
+in	O
+control	O
+or	O
+KCREB	B-GENE
+-	O
+transfected	O
+cells	O
+before	O
+or	O
+after	O
+treatment	O
+with	O
+Tg	O
+.	O
+
+Tyrosine	O
+112	O
+of	O
+latent	B-GENE
+membrane	I-GENE
+protein	I-GENE
+2A	I-GENE
+is	O
+essential	O
+for	O
+protein	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+loading	O
+and	O
+regulation	O
+of	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+latency	O
+.	O
+
+To	O
+improve	O
+test	O
+efficiency	O
+,	O
+we	O
+modified	O
+our	O
+previously	O
+introduced	O
+contrast	O
+/	O
+color	O
+card	O
+test	O
+by	O
+including	O
+a	O
+patterned	O
+test	O
+stimulus	O
+and	O
+reducing	O
+the	O
+number	O
+of	O
+stimuli	O
+in	O
+both	O
+experimental	O
+phases	O
+.	O
+
+The	O
+defect	O
+in	O
+these	O
+proteins	O
+was	O
+also	O
+uniformly	O
+suppressed	O
+by	O
+either	O
+Mn2	O
++	O
+,	O
+or	O
+the	O
+Mu	B-GENE
+B	I-GENE
+protein	I-GENE
+in	O
+the	O
+presence	O
+of	O
+ATP	O
+and	O
+target	O
+DNA	O
+.	O
+
+Using	O
+homology	O
+cloning	O
+techniques	O
+,	O
+we	O
+identified	O
+a	O
+mouse	O
+homologue	O
+of	O
+E	B-GENE
+(	I-GENE
+Pc	I-GENE
+)	I-GENE
+,	O
+termed	O
+Epc1	B-GENE
+,	O
+a	O
+yeast	O
+protein	O
+that	O
+we	O
+name	O
+EPL1	B-GENE
+,	O
+and	O
+as	O
+well	O
+as	O
+additional	O
+ESTs	O
+from	O
+Caenorhabditis	O
+elegans	O
+,	O
+mice	O
+and	O
+humans	O
+.	O
+
+Second	O
+,	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+m8	I-GENE
+3	I-GENE
+'	I-GENE
+UTR	I-GENE
+strongly	O
+reduces	O
+accumulation	O
+of	O
+heterologous	O
+transcripts	O
+in	O
+vivo	O
+,	O
+an	O
+activity	O
+that	O
+requires	O
+its	O
+K	O
+box	O
+sequences	O
+.	O
+
+In	O
+particular	O
+,	O
+unc	B-GENE
+-	I-GENE
+86	I-GENE
+encodes	O
+a	O
+POU	B-GENE
+-	I-GENE
+type	I-GENE
+homeodomain	I-GENE
+protein	I-GENE
+needed	O
+for	O
+the	O
+production	O
+of	O
+the	O
+touch	O
+cells	O
+,	O
+while	O
+mec	B-GENE
+-	I-GENE
+3	I-GENE
+encodes	O
+a	O
+LIM	B-GENE
+-	I-GENE
+type	I-GENE
+homeodomain	I-GENE
+protein	I-GENE
+needed	O
+for	O
+the	O
+differentiation	O
+of	O
+the	O
+touch	O
+cells	O
+.	O
+
+During	O
+the	O
+2h	O
+resuscitation	O
+period	O
+,	O
+extracellular	O
+aspartate	O
+and	O
+glutamate	O
+concentrations	O
+in	O
+the	O
+cerebral	O
+striatum	O
+were	O
+higher	O
+during	O
+hypoxaemic	O
+resuscitation	O
+(	O
+p	O
+=	O
+0	O
+.	O
+044	O
+and	O
+p	O
+=	O
+0	O
+.	O
+055	O
+,	O
+respectively	O
+)	O
+than	O
+during	O
+resuscitation	O
+with	O
+21	O
+%	O
+O2	O
+or	O
+100	O
+%	O
+O2	O
+,	O
+suggesting	O
+an	O
+unfavourable	O
+accumulation	O
+of	O
+potent	O
+excitotoxins	O
+during	O
+hypoxaemic	O
+resuscitation	O
+.	O
+
+Furthermore	O
+,	O
+phosphatidylinositol	O
+(	O
+3	O
+,	O
+4	O
+,	O
+5	O
+)	O
+trisphosphate	O
+specifically	O
+stimulates	O
+the	O
+activity	O
+of	O
+ILK	B-GENE
+in	O
+vitro	O
+,	O
+and	O
+in	O
+addition	O
+,	O
+membrane	O
+targetted	O
+constitutively	O
+active	O
+Pi	B-GENE
+(	I-GENE
+3	I-GENE
+)	I-GENE
+K	I-GENE
+activates	O
+ILK	B-GENE
+in	O
+vivo	O
+.	O
+
+Transfection	O
+and	O
+in	O
+vitro	O
+binding	O
+studies	O
+identified	O
+within	O
+HEFT1	B-GENE
+a	I-GENE
+promoter	I-GENE
+whose	O
+basal	O
+activity	O
+required	O
+a	O
+GC	O
+box	O
+activated	O
+by	O
+Sp1	B-GENE
+or	O
+Sp3	B-GENE
+.	O
+
+Plasma	O
+was	O
+tested	O
+before	O
+and	O
+after	O
+(	O
+14	O
++	O
+/	O
+-	O
+7	O
+.	O
+5	O
+[	O
+SD	O
+]	O
+days	O
+)	O
+surgery	O
+for	O
+IgG	B-GENE
+antibodies	I-GENE
+to	O
+the	O
+complex	O
+of	O
+heparin	B-GENE
+/	I-GENE
+platelet	I-GENE
+factor	I-GENE
+4	I-GENE
+,	O
+using	O
+a	O
+standardized	O
+,	O
+validated	O
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+(	O
+ELISA	O
+)	O
+.	O
+
+The	O
+FAS	B-GENE
+promoter	I-GENE
+was	O
+up	O
+-	O
+regulated	O
+by	O
+insulin	B-GENE
+through	O
+the	O
+proximal	O
+insulin	B-GENE
+response	I-GENE
+sequence	I-GENE
+containing	O
+an	O
+E	O
+-	O
+box	O
+motif	O
+at	O
+the	O
+-	O
+65	O
+-	O
+base	O
+pair	O
+position	O
+.	O
+
+The	O
+effect	O
+of	O
+independent	O
+predictors	O
+on	O
+survival	O
+was	O
+examined	O
+in	O
+a	O
+Cox	O
+regression	O
+model	O
+with	O
+adjustment	O
+for	O
+existing	O
+illnesses	O
+.	O
+
+Effects	O
+of	O
+rhG	B-GENE
+-	I-GENE
+CSF	I-GENE
+on	O
+neutrophil	O
+functions	O
+and	O
+survival	O
+in	O
+sepsis	O
+induced	O
+diabetic	O
+rats	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+purpose	O
+of	O
+this	O
+article	O
+is	O
+to	O
+review	O
+balance	O
+instruments	O
+developed	O
+within	O
+the	O
+past	O
+10	O
+years	O
+that	O
+can	O
+be	O
+used	O
+in	O
+the	O
+clinic	O
+or	O
+home	O
+environment	O
+.	O
+
+CASE	O
+REPORT	O
+:	O
+We	O
+observed	O
+a	O
+congenital	O
+skin	O
+defect	O
+located	O
+exclusively	O
+on	O
+the	O
+trunk	O
+.	O
+
+Anastrozole	O
+is	O
+the	O
+first	O
+aromatase	B-GENE
+inhibitor	O
+to	O
+show	O
+a	O
+significant	O
+survival	O
+advantage	O
+over	O
+megestrol	O
+acetate	O
+in	O
+post	O
+-	O
+menopausal	O
+women	O
+with	O
+advanced	O
+breast	O
+cancer	O
+.	O
+
+W	O
+.	O
+
+Moritta	O
+)	O
+and	O
+contains	O
+Bis	O
+-	O
+GMA	O
+.	O
+
+Mutation	O
+of	O
+either	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+or	O
+the	O
+ets	B-GENE
+component	O
+of	O
+this	O
+site	O
+also	O
+prevented	O
+promoter	O
+activity	O
+in	O
+SMCs	O
+.	O
+
+ANIMALS	O
+:	O
+Fifty	O
+dogs	O
+with	O
+naturally	O
+developing	O
+DM	O
+.	O
+
+Surprisingly	O
+,	O
+double	O
+mutants	O
+of	O
+the	O
+shy2	B-GENE
+-	I-GENE
+1D	I-GENE
+mutant	I-GENE
+with	O
+the	O
+phytochrome	B-GENE
+-	O
+deficient	O
+mutants	O
+hy2	B-GENE
+,	O
+hy3	B-GENE
+(	O
+phyB	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+fre1	B-GENE
+-	I-GENE
+1	I-GENE
+(	O
+phyA	B-GENE
+-	I-GENE
+201	I-GENE
+)	O
+showed	O
+reduced	O
+photomorphogenic	O
+response	O
+in	O
+darkness	O
+with	O
+a	O
+longer	O
+hypocotyl	O
+,	O
+a	O
+longer	O
+inflorescence	O
+stem	O
+,	O
+and	O
+a	O
+lower	O
+level	O
+expression	O
+of	O
+the	O
+CAB	B-GENE
+gene	I-GENE
+than	O
+the	O
+shy2	B-GENE
+-	I-GENE
+1D	I-GENE
+single	I-GENE
+mutant	I-GENE
+.	O
+
+Laser	O
+ablation	O
+has	O
+been	O
+employed	O
+as	O
+a	O
+therapeutic	O
+measure	O
+for	O
+chronic	O
+pulmonary	O
+emphysema	O
+.	O
+
+The	O
+SH2	O
+-	O
+containing	O
+adapter	O
+protein	O
+GRB10	B-GENE
+interacts	O
+with	O
+BCR	B-GENE
+-	O
+ABL	B-GENE
+.	O
+
+Saccharomyces	O
+cerevisiae	O
+contains	O
+four	O
+known	O
+acyl	B-GENE
+-	I-GENE
+CoA	I-GENE
+synthetases	I-GENE
+(	O
+fatty	B-GENE
+acid	I-GENE
+activation	I-GENE
+proteins	I-GENE
+,	O
+Faaps	B-GENE
+)	O
+.	O
+
+We	O
+recently	O
+reported	O
+a	O
+placenta	O
+-	O
+specific	O
+enhancer	O
+in	O
+the	O
+human	B-GENE
+leukemia	I-GENE
+inhibitory	I-GENE
+factor	I-GENE
+receptor	I-GENE
+(	O
+LIFR	B-GENE
+)	O
+gene	O
+and	O
+now	O
+show	O
+detailed	O
+characterization	O
+of	O
+the	O
+226	O
+-	O
+base	O
+pair	O
+enhancer	O
+(	O
+-	O
+4625	O
+/	O
+-	O
+4400	O
+nucleotides	O
+)	O
+.	O
+
+Copyright	O
+1998	O
+Elsevier	O
+Science	O
+B	O
+.	O
+V	O
+.	O
+
+It	O
+may	O
+be	O
+time	O
+to	O
+reevaluate	O
+the	O
+dichotomy	O
+between	O
+AD	O
+and	O
+VaD	O
+.	O
+
+Clone	O
+39	O
+was	O
+a	O
+homolog	O
+of	O
+CONSTANS	B-GENE
+,	O
+which	O
+is	O
+a	O
+gene	O
+involved	O
+in	O
+controlling	O
+the	O
+flowering	O
+time	O
+in	O
+Arabidopsis	O
+.	O
+
+The	O
+effects	O
+of	O
+high	O
+intensity	O
+light	O
+emissions	O
+,	O
+produced	O
+by	O
+a	O
+novel	O
+pulsed	O
+power	O
+energization	O
+technique	O
+(	O
+PPET	O
+)	O
+,	O
+on	O
+the	O
+survival	O
+of	O
+bacterial	O
+populations	O
+of	O
+verocytotoxigenic	O
+Escherichia	O
+coli	O
+(	O
+serotype	O
+0157	O
+:	O
+H7	O
+)	O
+and	O
+Listeria	O
+monocytogenes	O
+(	O
+serotype	O
+4b	O
+)	O
+were	O
+investigated	O
+.	O
+
+Multiple	O
+chemical	O
+sensitivity	O
+(	O
+MCS	O
+)	O
+is	O
+a	O
+syndrome	O
+in	O
+which	O
+multiple	O
+symptoms	O
+reportedly	O
+occur	O
+with	O
+low	O
+-	O
+level	O
+chemical	O
+exposure	O
+.	O
+
+POU	B-GENE
+-	I-GENE
+domain	I-GENE
+proteins	I-GENE
+,	O
+such	O
+as	O
+the	O
+pituitary	B-GENE
+-	I-GENE
+specific	I-GENE
+factor	I-GENE
+Pit	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+are	O
+members	O
+of	O
+the	O
+homeodomain	B-GENE
+family	I-GENE
+of	O
+proteins	O
+which	O
+are	O
+important	O
+in	O
+development	O
+and	O
+homeostasis	O
+,	O
+acting	O
+constitutively	O
+or	O
+in	O
+response	O
+to	O
+signal	O
+-	O
+transduction	O
+pathways	O
+to	O
+either	O
+repress	O
+or	O
+activate	O
+the	O
+expression	O
+of	O
+specific	O
+genes	O
+.	O
+
+Wild	O
+-	O
+type	O
+and	O
+mutant	O
+MyoD	B-GENE
+were	O
+introduced	O
+into	O
+cells	O
+using	O
+an	O
+E1	B-GENE
+,	O
+E3	B-GENE
+-	O
+deleted	O
+adenoviral	O
+vector	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+Thr115	O
+may	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+MyoD	B-GENE
+function	O
+under	O
+conditions	O
+of	O
+high	O
+mitogenesis	O
+.	O
+
+This	O
+and	O
+previous	O
+results	O
+suggest	O
+that	O
+the	O
+CRE	O
+and	O
+Sp1	B-GENE
+site	I-GENE
+may	O
+synergistically	O
+activate	O
+TH	B-GENE
+transcription	O
+in	O
+a	O
+promoter	O
+context	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Endoscopic	O
+examinations	O
+,	O
+peripheral	O
+white	O
+blood	O
+cell	O
+(	O
+WBC	O
+)	O
+counts	O
+,	O
+and	O
+assays	O
+of	O
+myeloperoxidase	B-GENE
+activity	O
+(	O
+MPO	B-GENE
+)	O
+in	O
+homogenates	O
+of	O
+colon	O
+mucosa	O
+were	O
+performed	O
+after	O
+one	O
+week	O
+(	O
+4	O
+%	O
+DSS	O
+model	O
+)	O
+and	O
+eight	O
+weeks	O
+(	O
+1	O
+%	O
+DSS	O
+model	O
+)	O
+.	O
+
+T7	O
+transcription	O
+could	O
+be	O
+manipulated	O
+to	O
+achieve	O
+different	O
+levels	O
+of	O
+constitutive	O
+expression	O
+,	O
+through	O
+the	O
+use	O
+of	O
+promoter	O
+mutations	O
+.	O
+
+The	O
+primers	O
+were	O
+degenerate	O
+sets	O
+of	O
+oligonucleotides	O
+derived	O
+from	O
+known	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+PBAN	B-GENE
+precursor	I-GENE
+.	O
+
+Plants	O
+transformed	O
+with	O
+the	O
+35S	B-GENE
+-	O
+1	B-GENE
+-	I-GENE
+sst	I-GENE
+construct	O
+accumulated	O
+the	O
+oligofructans	O
+1	O
+-	O
+kestose	O
+(	O
+GF2	O
+)	O
+,	O
+1	O
+,	O
+1	O
+-	O
+nystose	O
+(	O
+GF3	O
+)	O
+and	O
+1	O
+,	O
+1	O
+,	O
+1	O
+-	O
+fructosylnystose	O
+(	O
+GF4	O
+)	O
+.	O
+
+Based	O
+on	O
+the	O
+comparison	O
+of	O
+the	O
+predicted	O
+amino	O
+acid	O
+sequences	O
+of	O
+1	B-GENE
+-	I-GENE
+sst	I-GENE
+and	O
+1	B-GENE
+-	I-GENE
+fft	I-GENE
+with	O
+those	O
+of	O
+other	O
+plant	O
+fructosyl	B-GENE
+transferase	I-GENE
+genes	I-GENE
+,	O
+we	O
+postulate	O
+that	O
+both	O
+plant	O
+fructan	B-GENE
+genes	I-GENE
+have	O
+evolved	O
+from	O
+plant	O
+invertase	B-GENE
+genes	O
+.	O
+
+However	O
+,	O
+ICK1	B-GENE
+was	O
+induced	O
+by	O
+ABA	O
+,	O
+and	O
+along	O
+with	O
+ICK1	B-GENE
+induction	O
+there	O
+was	O
+a	O
+decrease	O
+in	O
+Cdc2	B-GENE
+-	I-GENE
+like	I-GENE
+histone	B-GENE
+H1	I-GENE
+kinase	I-GENE
+activity	O
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+that	O
+swa5	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+a	O
+new	O
+temperature	O
+-	O
+sensitive	O
+allele	O
+of	O
+the	O
+clathrin	B-GENE
+heavy	I-GENE
+chain	I-GENE
+gene	I-GENE
+(	O
+chc1	B-GENE
+-	I-GENE
+5	I-GENE
+)	O
+,	O
+which	O
+carries	O
+a	O
+frameshift	O
+mutation	O
+near	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+CHC1	B-GENE
+open	O
+reading	O
+frame	O
+.	O
+
+We	O
+have	O
+determined	O
+the	O
+molecular	O
+lesions	O
+of	O
+nine	O
+Scm	B-GENE
+mutant	I-GENE
+alleles	I-GENE
+,	O
+which	O
+identify	O
+functional	O
+requirements	O
+for	O
+specific	O
+domains	O
+.	O
+
+Intriguingly	O
+,	O
+three	O
+hypomorphic	O
+Scm	B-GENE
+mutations	O
+,	O
+which	O
+map	O
+within	O
+an	O
+mbt	B-GENE
+repeat	I-GENE
+,	O
+interact	O
+with	O
+PcG	B-GENE
+mutations	I-GENE
+more	O
+strongly	O
+than	O
+do	O
+Scm	B-GENE
+null	O
+alleles	O
+.	O
+
+Northern	O
+analysis	O
+revealed	O
+no	O
+detectable	O
+expression	O
+of	O
+the	O
+transcript	O
+in	O
+diapause	O
+-	O
+or	O
+nondiapause	O
+-	O
+programmed	O
+wandering	O
+larvae	O
+,	O
+and	O
+only	O
+trace	O
+expression	O
+in	O
+nondiapausing	O
+pupae	O
+.	O
+
+Besides	O
+the	O
+characterization	O
+and	O
+discussion	O
+of	O
+the	O
+experimental	O
+setup	O
+used	O
+,	O
+the	O
+rate	O
+constants	O
+obtained	O
+are	O
+discussed	O
+and	O
+compared	O
+with	O
+estimated	O
+values	O
+.	O
+
+The	O
+presence	O
+of	O
+PDZ	B-GENE
+and	O
+SAM	O
+domains	O
+in	O
+the	O
+KS5	B-GENE
+protein	I-GENE
+suggests	O
+that	O
+it	O
+may	O
+act	O
+as	O
+a	O
+molecular	O
+adaptor	O
+,	O
+promoting	O
+and	O
+relaying	O
+information	O
+in	O
+a	O
+signal	O
+transduction	O
+pathway	O
+.	O
+
+BACKGROUND	O
+:	O
+Fluoroquinolones	O
+(	O
+FQ	O
+)	O
+are	O
+contraindicated	O
+in	O
+children	O
+because	O
+of	O
+the	O
+risk	O
+of	O
+cartilage	O
+damage	O
+.	O
+
+In	O
+analyses	O
+with	O
+control	O
+for	O
+multiple	O
+variables	O
+,	O
+relative	O
+risk	O
+for	O
+microalbuminuria	O
+(	O
+urinary	O
+albumin	B-GENE
+excretion	O
+,	O
+20	O
+-	O
+199	O
+microg	O
+/	O
+min	O
+)	O
+in	O
+men	O
+and	O
+women	O
+was	O
+2	O
+.	O
+51	O
+and	O
+1	O
+.	O
+62	O
+,	O
+respectively	O
+,	O
+with	O
+18	O
+mm	O
+Hg	O
+higher	O
+(	O
+1	O
+SD	O
+)	O
+systolic	O
+blood	O
+pressure	O
+;	O
+2	O
+.	O
+25	O
+and	O
+2	O
+.	O
+10	O
+,	O
+respectively	O
+,	O
+with	O
+1	O
+.	O
+0	O
+-	O
+mmol	O
+/	O
+L	O
+(	O
+40	O
+mg	O
+/	O
+dL	O
+)	O
+higher	O
+plasma	O
+cholesterol	O
+level	O
+;	O
+1	O
+.	O
+99	O
+and	O
+1	O
+.	O
+91	O
+,	O
+respectively	O
+,	O
+for	O
+smokers	O
+vs	O
+nonsmokers	O
+;	O
+and	O
+1	O
+.	O
+83	O
+and	O
+1	O
+.	O
+33	O
+,	O
+respectively	O
+,	O
+with	O
+4	O
+kg	O
+/	O
+m2	O
+higher	O
+body	O
+mass	O
+index	O
+.	O
+
+However	O
+,	O
+while	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+and	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+both	O
+induced	O
+nuclear	O
+binding	O
+of	O
+the	O
+Rel	B-GENE
+proteins	I-GENE
+p50	B-GENE
+and	O
+p65	B-GENE
+to	O
+an	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+consensus	I-GENE
+oligonucleotide	I-GENE
+in	O
+gel	O
+shift	O
+assays	O
+and	O
+caused	O
+transient	O
+degradation	O
+of	O
+inhibitor	B-GENE
+of	I-GENE
+NF	I-GENE
+-	I-GENE
+kappaB	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+IkappaB	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+in	O
+the	O
+cytoplasm	O
+of	O
+myofibroblasts	O
+,	O
+only	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+upregulated	O
+PDGF	B-GENE
+-	I-GENE
+Ralpha	I-GENE
+.	O
+
+Cotransfections	O
+with	O
+ATF	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+HNF	B-GENE
+-	I-GENE
+4	I-GENE
+expression	O
+plasmids	O
+resulted	O
+in	O
+additive	O
+transactivation	O
+of	O
+the	O
+apoCIII	B-GENE
+promoter	I-GENE
+.	O
+
+Phosphocreatine	O
+hydrolysis	O
+during	O
+submaximal	O
+exercise	O
+:	O
+the	O
+effect	O
+of	O
+FIO2	O
+.	O
+
+Pseudocontact	O
+shifts	O
+arise	O
+from	O
+the	O
+isotropic	O
+reorientational	O
+average	O
+of	O
+the	O
+dipolar	O
+coupling	O
+between	O
+unpaired	O
+electron	O
+and	O
+nuclei	O
+,	O
+in	O
+the	O
+presence	O
+of	O
+magnetic	O
+susceptibility	O
+anisotropy	O
+.	O
+
+GETS	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+expressed	O
+in	O
+many	O
+tissues	O
+,	O
+but	O
+is	O
+enriched	O
+in	O
+retina	O
+and	O
+brain	O
+.	O
+
+The	O
+interaction	O
+of	O
+U1	B-GENE
+-	I-GENE
+70K	I-GENE
+with	O
+the	O
+SRZ	B-GENE
+proteins	I-GENE
+is	O
+confirmed	O
+further	O
+in	O
+vitro	O
+using	O
+a	O
+blot	O
+overlay	O
+assay	O
+.	O
+
+The	O
+major	O
+phenotypes	O
+resulting	O
+from	O
+Fab1p	B-GENE
+kinase	I-GENE
+inactivation	O
+include	O
+temperature	O
+-	O
+sensitive	O
+growth	O
+,	O
+vacuolar	O
+acidification	O
+defects	O
+,	O
+and	O
+dramatic	O
+increases	O
+in	O
+vacuolar	O
+size	O
+.	O
+
+Interestingly	O
+,	O
+an	O
+antibody	O
+against	O
+N	B-GENE
+-	I-GENE
+SMase	I-GENE
+can	O
+abrogate	O
+Ox	B-GENE
+-	I-GENE
+LDL	I-GENE
+-	O
+and	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+-	O
+induced	O
+apoptosis	O
+and	O
+therefore	O
+may	O
+be	O
+useful	O
+for	O
+in	O
+vivo	O
+studies	O
+of	O
+apoptosis	O
+in	O
+experimental	O
+animals	O
+.	O
+
+We	O
+found	O
+that	O
+virulent	O
+Ngo	O
+strains	O
+induce	O
+phosphorylation	O
+and	O
+activation	O
+of	O
+JNK	B-GENE
+but	O
+not	O
+of	O
+p38	B-GENE
+kinase	O
+.	O
+
+Focused	O
+beams	O
+of	O
+classical	O
+light	O
+ablate	O
+elements	O
+of	O
+the	O
+cell	O
+division	O
+machinery	O
+and	O
+switch	O
+the	O
+beating	O
+of	O
+hearts	O
+on	O
+a	O
+cellular	O
+basis	O
+.	O
+
+The	O
+human	O
+T	O
+cell	O
+lymphotropic	O
+retrovirus	O
+type	O
+I	O
+(	O
+HTLV	O
+-	O
+I	O
+)	O
+trans	O
+-	O
+activator	O
+,	O
+Tax	B-GENE
+,	O
+interacts	O
+specifically	O
+with	O
+the	O
+basic	B-GENE
+-	I-GENE
+domain	I-GENE
+/	I-GENE
+leucine	I-GENE
+-	I-GENE
+zipper	I-GENE
+(	I-GENE
+bZip	I-GENE
+)	I-GENE
+protein	I-GENE
+,	O
+cAMP	B-GENE
+response	I-GENE
+element	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+CREB	B-GENE
+)	O
+,	O
+bound	O
+to	O
+the	O
+viral	B-GENE
+Tax	I-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+consisting	O
+of	O
+three	O
+imperfect	O
+21	O
+-	O
+base	O
+pair	O
+repeats	O
+,	O
+each	O
+with	O
+a	O
+cAMP	O
+response	O
+element	O
+core	O
+flanked	O
+by	O
+G	O
+/	O
+C	O
+-	O
+rich	O
+sequences	O
+.	O
+
+This	O
+sequence	O
+is	O
+very	O
+similar	O
+to	O
+the	O
+insulin	B-GENE
+response	I-GENE
+sequence	I-GENE
+found	O
+in	O
+the	O
+regulatory	O
+region	O
+of	O
+other	O
+genes	O
+negatively	O
+regulated	O
+by	O
+insulin	B-GENE
+such	O
+as	O
+those	O
+encoding	O
+phosphoenolpyruvate	B-GENE
+carboxykinase	I-GENE
+,	O
+tyrosine	B-GENE
+aminotransferase	I-GENE
+,	O
+and	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+.	O
+
+The	O
+murine	B-GENE
+facilitative	I-GENE
+glucose	I-GENE
+transporter	I-GENE
+isoform	I-GENE
+3	I-GENE
+(	O
+Glut	B-GENE
+3	I-GENE
+)	O
+is	O
+developmentally	O
+regulated	O
+and	O
+is	O
+predominantly	O
+expressed	O
+in	O
+neurons	O
+and	O
+trophoblasts	O
+.	O
+
+However	O
+,	O
+changing	O
+the	O
+half	O
+-	O
+site	O
+to	O
+the	O
+consensus	O
+sequence	O
+AGGTCA	O
+(	O
+IRper	O
+-	O
+1	O
+)	O
+increased	O
+binding	O
+of	O
+AaEcR	B-GENE
+.	I-GENE
+AaUSP	I-GENE
+10	O
+-	O
+fold	O
+over	O
+IRhsp	O
+-	O
+1	O
+and	O
+,	O
+at	O
+the	O
+same	O
+time	O
+,	O
+reduced	O
+the	O
+stringency	O
+of	O
+the	O
+spacer	O
+length	O
+requirement	O
+,	O
+with	O
+IRper	O
+-	O
+0	O
+to	O
+IRper	O
+-	O
+5	O
+showing	O
+detectable	O
+binding	O
+.	O
+
+The	O
+levels	O
+of	O
+transactivation	O
+are	O
+correlated	O
+with	O
+the	O
+respective	O
+binding	O
+affinities	O
+of	O
+the	O
+response	O
+elements	O
+(	O
+IRper	O
+-	O
+1	O
+>	O
+DR	O
+-	O
+4	O
+>	O
+IRhsp	O
+-	O
+1	O
+)	O
+.	O
+
+The	O
+high	O
+density	O
+of	O
+tegumental	O
+spines	O
+on	O
+posterior	O
+half	O
+of	O
+the	O
+body	O
+and	O
+the	O
+distribution	O
+of	O
+type	O
+II	O
+papillae	O
+on	O
+dorsal	O
+surface	O
+are	O
+considered	O
+to	O
+be	O
+characteristic	O
+of	O
+C	O
+.	O
+armatus	O
+.	O
+
+Inactivation	O
+of	O
+p53	B-GENE
+but	O
+not	O
+p73	B-GENE
+by	O
+adenovirus	B-GENE
+type	I-GENE
+5	I-GENE
+E1B	I-GENE
+55	I-GENE
+-	I-GENE
+kilodalton	I-GENE
+and	I-GENE
+E4	I-GENE
+34	I-GENE
+-	I-GENE
+kilodalton	I-GENE
+oncoproteins	I-GENE
+.	O
+
+The	O
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+transactivator	I-GENE
+Zta	I-GENE
+triggers	O
+lytic	O
+gene	O
+expression	O
+and	O
+is	O
+essential	O
+for	O
+replication	O
+of	O
+the	O
+lytic	O
+origin	O
+,	O
+oriLyt	O
+.	O
+
+Cotransfection	O
+of	O
+the	O
+helicase	B-GENE
+-	O
+primase	B-GENE
+proteins	O
+,	O
+one	O
+of	O
+which	O
+was	O
+fused	O
+to	O
+a	O
+heterologous	O
+activation	O
+domain	O
+,	O
+led	O
+to	O
+Zta	B-GENE
+-	O
+dependent	O
+superactivation	O
+of	O
+CAT	B-GENE
+expression	O
+.	O
+
+A	O
+single	O
+rectal	O
+dose	O
+of	O
+25	O
+mg	O
+/	O
+kg	O
+will	O
+obtain	O
+this	O
+lower	O
+concentration	O
+within	O
+1	O
+h	O
+of	O
+administration	O
+and	O
+maintain	O
+it	O
+for	O
+up	O
+to	O
+6	O
+h	O
+.	O
+
+Although	O
+YopH	B-GENE
+is	O
+a	O
+highly	O
+active	O
+PTP	B-GENE
+,	O
+it	O
+preferentially	O
+targets	O
+a	O
+subset	O
+of	O
+tyrosine	O
+-	O
+phosphorylated	O
+proteins	O
+in	O
+host	O
+cells	O
+,	O
+including	O
+p130Cas	B-GENE
+.	O
+
+Phylogenetic	O
+position	O
+of	O
+the	O
+Phacotaceae	O
+within	O
+the	O
+Chlamydophyceaeas	O
+revealed	O
+by	O
+analysis	O
+of	O
+18S	B-GENE
+rDNA	I-GENE
+and	O
+rbcL	B-GENE
+sequences	I-GENE
+.	O
+
+The	O
+activation	O
+and	O
+injury	O
+of	O
+endothelial	O
+cells	O
+induced	O
+by	O
+TNF	B-GENE
+and	O
+other	O
+proinflammatory	O
+cytokines	O
+may	O
+underlie	O
+the	O
+local	O
+effects	O
+of	O
+these	O
+mediators	O
+in	O
+vivo	O
+.	O
+
+A	O
+technique	O
+for	O
+thermal	O
+imaging	O
+of	O
+the	O
+animal	O
+and	O
+human	O
+brain	O
+cortex	O
+using	O
+an	O
+infrared	O
+optical	O
+system	O
+is	O
+described	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+THOV	B-GENE
+NP	I-GENE
+contains	O
+a	O
+motif	O
+(	O
+KRxxxxxxxxxKTKK	O
+)	O
+at	O
+amino	O
+acid	O
+positions	O
+179	O
+-	O
+193	O
+that	O
+represents	O
+a	O
+classical	O
+bipartite	O
+nuclear	O
+localization	O
+signal	O
+(	O
+NLS	O
+)	O
+.	O
+
+As	O
+PP2A	B-GENE
+exerts	O
+a	O
+range	O
+of	O
+cellular	O
+functions	O
+including	O
+cell	O
+cycle	O
+regulation	O
+and	O
+cell	O
+fate	O
+determination	O
+,	O
+we	O
+were	O
+surprised	O
+to	O
+find	O
+that	O
+these	O
+embryos	O
+develop	O
+normally	O
+until	O
+postimplantation	O
+,	O
+around	O
+embryonic	O
+day	O
+5	O
+.	O
+5	O
+/	O
+6	O
+.	O
+0	O
+.	O
+
+The	O
+most	O
+frequent	O
+risk	O
+factor	O
+for	O
+ischaemic	O
+was	O
+hypertension	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+anthraquinone	O
+sennoside	O
+B	O
+and	O
+rhein	O
+are	O
+weakly	O
+genotoxic	O
+.	O
+
+16	O
+subjects	O
+were	O
+repatch	O
+tested	O
+to	O
+ethylmercury	O
+chloride	O
+(	O
+EtHgCl	O
+)	O
+and	O
+to	O
+solutions	O
+containing	O
+EtHgCl	O
+mixed	O
+with	O
+L	O
+-	O
+cysteine	O
+and	O
+glutathione	O
+,	O
+respectively	O
+.	O
+
+The	O
+carboxyl	O
+-	O
+terminal	O
+portion	O
+of	O
+UKLF	B-GENE
+contains	O
+three	O
+zinc	O
+fingers	O
+of	O
+the	O
+Cys2	O
+-	O
+His2	O
+type	O
+and	O
+binds	O
+in	O
+vitro	O
+to	O
+the	O
+CACCC	O
+motif	O
+of	O
+the	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+promoter	I-GENE
+and	O
+to	O
+the	O
+Sp1	B-GENE
+recognition	I-GENE
+sequence	I-GENE
+.	O
+
+We	O
+have	O
+recently	O
+identified	O
+a	O
+mouse	O
+enzyme	O
+termed	O
+gamma	B-GENE
+-	I-GENE
+glutamyl	I-GENE
+leukotrienase	I-GENE
+(	O
+GGL	B-GENE
+)	O
+that	O
+converts	O
+leukotriene	O
+C4	O
+(	O
+LTC4	O
+)	O
+to	O
+leukotriene	O
+D4	O
+(	O
+LTD4	O
+)	O
+.	O
+
+UGA	O
+codon	O
+position	O
+affects	O
+the	O
+efficiency	O
+of	O
+selenocysteine	O
+incorporation	O
+into	O
+glutathione	B-GENE
+peroxidase	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Forskolin	O
+significantly	O
+enhanced	O
+heregulin	B-GENE
+-	O
+stimulated	O
+expression	O
+of	O
+cyclin	B-GENE
+D	I-GENE
+and	O
+phosphorylation	O
+of	O
+the	O
+retinoblastoma	B-GENE
+gene	I-GENE
+product	I-GENE
+.	O
+
+The	O
+ARF	B-GENE
+promoter	I-GENE
+was	O
+also	O
+found	O
+to	O
+be	O
+highly	O
+responsive	O
+to	O
+E2F1	B-GENE
+expression	O
+,	O
+in	O
+keeping	O
+with	O
+previous	O
+results	O
+at	O
+the	O
+RNA	O
+level	O
+.	O
+
+Observers	O
+with	O
+brain	O
+injury	O
+and	O
+control	O
+participants	O
+performed	O
+a	O
+vigilance	O
+task	O
+during	O
+which	O
+they	O
+received	O
+periodic	O
+whiffs	O
+of	O
+unscented	O
+air	O
+or	O
+air	O
+scented	O
+with	O
+peppermint	O
+.	O
+
+A	O
+simple	O
+analytical	O
+method	O
+for	O
+l	O
+-	O
+menthol	O
+by	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatography	O
+with	O
+a	O
+polarized	O
+photometric	O
+detector	O
+was	O
+established	O
+.	O
+
+After	O
+measuring	O
+baseline	O
+Vmca	O
+at	O
+a	O
+partial	O
+pressure	O
+of	O
+carbon	O
+dioxide	O
+in	O
+arterial	O
+blood	O
+(	O
+PaCO2	O
+)	O
+of	O
+37	O
+.	O
+7	O
++	O
+/	O
+-	O
+4	O
+.	O
+5	O
+mmHg	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+,	O
+measurements	O
+were	O
+repeated	O
+at	O
+a	O
+PaCO	O
+of	O
+44	O
+.	O
+2	O
++	O
+/	O
+-	O
+3	O
+.	O
+8	O
+mmHg	O
+,	O
+and	O
+the	O
+carbon	O
+dioxide	O
+reactivity	O
+(	O
+absolute	O
+value	O
+:	O
+cm	O
+x	O
+s	O
+(	O
+-	O
+1	O
+)	O
+x	O
+mmHg	O
+(	O
+-	O
+1	O
+)	O
+;	O
+relative	O
+value	O
+:	O
+percentage	O
+of	O
+baseline	O
+Vmca	O
+/	O
+mmHg	O
+)	O
+was	O
+calculated	O
+.	O
+
+Multivariate	O
+Cox	O
+survival	O
+analysis	O
+identified	O
+baseline	O
+EF	O
+<	O
+or	O
+=	O
+30	O
+%	O
+,	O
+presence	O
+of	O
+significant	O
+mitral	O
+regurgitation	O
+(	O
+>	O
+2	O
++	O
+)	O
+before	O
+ablation	O
+,	O
+and	O
+failure	O
+to	O
+exhibit	O
+improved	O
+cardiac	O
+performance	O
+by	O
+1	O
+month	O
+after	O
+ablation	O
+as	O
+the	O
+only	O
+independent	O
+predictors	O
+of	O
+death	O
+.	O
+
+We	O
+have	O
+developed	O
+a	O
+new	O
+method	O
+for	O
+estimation	O
+of	O
+regional	O
+CBF	O
+(	O
+rCBF	O
+)	O
+and	O
+cerebrovascular	O
+reserve	O
+capacity	O
+on	O
+a	O
+pixel	O
+-	O
+by	O
+-	O
+pixel	O
+basis	O
+by	O
+means	O
+of	O
+dynamic	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+MRI	O
+)	O
+.	O
+
+Cost	O
+-	O
+effectiveness	O
+analysis	O
+provides	O
+a	O
+rational	O
+means	O
+of	O
+allocating	O
+limited	O
+health	O
+care	O
+resources	O
+by	O
+allowing	O
+the	O
+comparison	O
+of	O
+the	O
+costs	O
+of	O
+lipid	O
+-	O
+lowering	O
+therapy	O
+,	O
+in	O
+particular	O
+,	O
+therapy	O
+with	O
+beta	B-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+beta	I-GENE
+-	I-GENE
+methylglutaryl	I-GENE
+-	I-GENE
+CoA	I-GENE
+(	I-GENE
+coenzyme	I-GENE
+A	I-GENE
+)	I-GENE
+reductase	I-GENE
+inhibitors	O
+(	O
+statins	O
+)	O
+,	O
+with	O
+the	O
+costs	O
+of	O
+atherosclerosis	O
+that	O
+could	O
+be	O
+prevented	O
+by	O
+lowering	O
+cholesterol	O
+.	O
+
+Although	O
+E2FBP1	B-GENE
+lacks	O
+the	O
+transactivation	O
+domain	O
+,	O
+it	O
+stimulates	O
+E2F	B-GENE
+site	O
+-	O
+dependent	O
+transcription	O
+in	O
+cooperation	O
+with	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Analysis	O
+of	O
+Msy2	B-GENE
+mRNA	I-GENE
+expression	O
+in	O
+prepubertal	O
+and	O
+adult	O
+mouse	O
+testes	O
+,	O
+and	O
+in	O
+isolated	O
+populations	O
+of	O
+germ	O
+cells	O
+,	O
+reveals	O
+maximal	O
+expression	O
+in	O
+postmeiotic	O
+round	O
+spermatids	O
+,	O
+a	O
+cell	O
+type	O
+with	O
+abundant	O
+amounts	O
+of	O
+stored	O
+messenger	O
+ribonucleoproteins	O
+.	O
+
+1	O
+in	O
+Ho	O
+Chi	O
+Minh	O
+City	O
+was	O
+studied	O
+by	O
+culture	O
+and	O
+latex	O
+agglutination	O
+of	O
+blood	O
+,	O
+cerebrospinal	O
+fluid	O
+,	O
+urine	O
+and	O
+pleural	O
+fluid	O
+.	O
+
+Glycogen	O
+synthesis	O
+and	O
+catabolism	O
+,	O
+gluconeogenesis	O
+,	O
+glycolysis	O
+,	O
+motility	O
+,	O
+cell	O
+surface	O
+properties	O
+and	O
+adherence	O
+are	O
+modulated	O
+by	O
+csrA	B-GENE
+in	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+,	O
+while	O
+the	O
+production	O
+of	O
+several	O
+secreted	O
+virulence	O
+factors	O
+,	O
+the	O
+plant	O
+hypersensitive	O
+response	O
+elicitor	O
+HrpN	B-GENE
+(	O
+Ecc	B-GENE
+)	O
+and	O
+,	O
+potentially	O
+,	O
+other	O
+secondary	O
+metabolites	O
+are	O
+regulated	O
+by	O
+rsmA	B-GENE
+in	I-GENE
+Erwinia	I-GENE
+carotovora	I-GENE
+.	O
+
+Deletion	O
+analysis	O
+revealed	O
+that	O
+the	O
+essential	O
+domain	O
+of	O
+this	O
+promoter	O
+,	O
+termed	O
+the	O
+ORF5	B-GENE
+/	I-GENE
+deltaX	I-GENE
+transcript	I-GENE
+promoter	I-GENE
+,	O
+mapped	O
+to	O
+nucleotides	O
+1525	O
+-	O
+1625	O
+.	O
+
+Some	O
+of	O
+the	O
+peptide	B-GENE
+:	I-GENE
+MBP	I-GENE
+fusions	I-GENE
+were	O
+also	O
+analyzed	O
+using	O
+surface	O
+plasmon	O
+resonance	O
+.	O
+
+Cardiac	B-GENE
+myosin	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+C	I-GENE
+(	O
+MyBP	B-GENE
+-	I-GENE
+C	I-GENE
+)	O
+:	O
+identification	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+and	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+phosphorylation	O
+sites	O
+.	O
+
+Analysis	O
+of	O
+chromosomal	O
+DNA	O
+sequence	O
+immediately	O
+downstream	O
+of	O
+the	O
+transposon	O
+insertion	O
+identified	O
+two	O
+open	O
+reading	O
+frames	O
+,	O
+designated	O
+csrR	B-GENE
+and	O
+csrS	B-GENE
+,	O
+which	O
+exhibited	O
+sequence	O
+similarity	O
+to	O
+bacterial	O
+two	O
+-	O
+component	O
+regulatory	O
+systems	O
+.	O
+
+We	O
+previously	O
+delineated	O
+a	O
+region	O
+in	O
+the	O
+fatty	B-GENE
+-	I-GENE
+acid	I-GENE
+synthase	I-GENE
+promoter	I-GENE
+,	O
+which	O
+was	O
+responsible	O
+for	O
+obesity	O
+-	O
+related	O
+overexpression	O
+of	O
+the	O
+fatty	B-GENE
+-	I-GENE
+acid	I-GENE
+synthase	I-GENE
+(	O
+FAS	B-GENE
+)	O
+gene	O
+,	O
+by	O
+negatively	O
+regulating	O
+the	O
+activity	O
+of	O
+the	O
+downstream	O
+promoter	O
+in	O
+lean	O
+but	O
+not	O
+obese	O
+rat	O
+fat	O
+cells	O
+.	O
+
+Finally	O
+,	O
+using	O
+in	O
+vitro	O
+binding	O
+studies	O
+,	O
+we	O
+showed	O
+that	O
+SREBP2	B-GENE
+was	O
+able	O
+to	O
+displace	O
+ADD1	B-GENE
+/	O
+SREBP1	B-GENE
+binding	O
+from	O
+the	O
+sterol	O
+regulatory	O
+element	O
+(	O
+SRE	O
+)	O
+site	O
+.	O
+
+Thus	O
+,	O
+IRF	B-GENE
+-	I-GENE
+7	I-GENE
+exhibits	O
+functional	O
+similarity	O
+to	O
+IRF	B-GENE
+-	I-GENE
+3	I-GENE
+;	O
+however	O
+,	O
+the	O
+preferential	O
+expression	O
+of	O
+IRF	B-GENE
+-	I-GENE
+7	I-GENE
+in	O
+lymphoid	O
+cells	O
+(	O
+the	O
+cell	O
+type	O
+that	O
+expresses	O
+IFNA	B-GENE
+)	O
+suggests	O
+that	O
+IRF	B-GENE
+-	I-GENE
+7	I-GENE
+may	O
+play	O
+a	O
+critical	O
+role	O
+in	O
+regulating	O
+the	O
+IFNA	B-GENE
+gene	I-GENE
+expression	O
+.	O
+
+J	O
+.	O
+
+PURPOSE	O
+:	O
+The	O
+role	O
+interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+)	O
+in	O
+the	O
+treatment	O
+of	O
+congenital	O
+thrombocytopenias	O
+is	O
+unknown	O
+.	O
+
+CKII	B-GENE
+as	O
+a	O
+CD44	B-GENE
+-	I-GENE
+associated	I-GENE
+serine	I-GENE
+kinase	I-GENE
+therefore	O
+may	O
+serve	O
+as	O
+an	O
+important	O
+molecule	O
+in	O
+a	O
+signaling	O
+cascade	O
+that	O
+produces	O
+a	O
+variety	O
+of	O
+cellular	O
+responses	O
+in	O
+MDA231	O
+breast	O
+cancer	O
+cells	O
+.	O
+
+Galphaq	B-GENE
+,	O
+Galpha12	B-GENE
+,	O
+and	O
+Galpha13	B-GENE
+,	O
+but	O
+not	O
+Galphai	B-GENE
+,	O
+activate	O
+SRF	B-GENE
+through	O
+RhoA	B-GENE
+.	O
+
+Additionally	O
+in	O
+seven	O
+subjects	O
+adrenaline	O
+(	O
+A	O
+)	O
+and	O
+noradrenaline	O
+(	O
+NA	O
+)	O
+concentrations	O
+were	O
+determined	O
+.	O
+
+Northern	O
+blot	O
+analyses	O
+show	O
+that	O
+the	O
+hBub1	B-GENE
+mRNA	I-GENE
+level	O
+is	O
+abundantly	O
+expressed	O
+in	O
+tissues	O
+or	O
+cells	O
+with	O
+a	O
+high	O
+mitotic	O
+index	O
+.	O
+
+We	O
+mapped	O
+two	O
+overlapping	O
+expressed	O
+sequence	O
+tag	O
+clones	O
+within	O
+a	O
+genomic	O
+contig	O
+on	O
+human	O
+chromosome	O
+5	O
+,	O
+band	O
+q31	O
+.	O
+
+Htra2	B-GENE
+-	I-GENE
+beta3	I-GENE
+is	O
+developmentally	O
+regulated	O
+and	O
+expressed	O
+predominantly	O
+in	O
+brain	O
+,	O
+liver	O
+testis	O
+,	O
+and	O
+weakly	O
+in	O
+kidney	O
+.	O
+
+Gng3lg	B-GENE
+transcripts	I-GENE
+are	O
+expressed	O
+in	O
+a	O
+variety	O
+of	O
+tissues	O
+including	O
+both	O
+brain	O
+and	O
+testes	O
+.	O
+
+Using	O
+an	O
+interspecific	O
+backcross	O
+panel	O
+,	O
+we	O
+localized	O
+both	O
+Gng3	B-GENE
+and	O
+Gng3lg	B-GENE
+to	O
+the	O
+same	O
+locus	O
+on	O
+chromosome	O
+19	O
+.	O
+
+We	O
+also	O
+raised	O
+a	O
+polyclonal	O
+antibody	O
+against	O
+the	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+fusion	I-GENE
+protein	I-GENE
+containing	O
+the	O
+NH2	O
+-	O
+terminal	O
+86	O
+amino	O
+acids	O
+of	O
+human	B-GENE
+NRAMP2	I-GENE
+.	O
+
+Inhibition	O
+of	O
+the	O
+apolipoprotein	B-GENE
+B	I-GENE
+mRNA	I-GENE
+editing	O
+enzyme	O
+-	O
+complex	O
+by	O
+hnRNP	B-GENE
+C1	I-GENE
+protein	I-GENE
+and	O
+40S	B-GENE
+hnRNP	I-GENE
+complexes	I-GENE
+.	O
+
+SRC	B-GENE
+-	I-GENE
+1	I-GENE
+can	O
+relieve	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+-	O
+mediated	O
+repression	O
+of	O
+GR	B-GENE
+activity	O
+.	O
+
+However	O
+the	O
+sequence	O
+surrounding	O
+the	O
+transcription	O
+start	O
+site	O
+CTCA	O
+(	O
++	O
+1	O
+)	O
+TTCC	O
+was	O
+similar	O
+to	O
+the	O
+consensus	O
+CTCA	O
+(	O
++	O
+1	O
+)	O
+NTCT	O
+(	O
+N	O
+is	O
+any	O
+nucleoside	O
+)	O
+for	O
+an	O
+initiator	O
+element	O
+found	O
+in	O
+terminal	B-GENE
+deoxynucleotidyltransferase	I-GENE
+and	O
+a	O
+number	O
+of	O
+other	O
+highly	O
+regulated	O
+genes	O
+.	O
+
+Expression	O
+of	O
+a	O
+dominant	O
+-	O
+negative	O
+mutant	O
+of	O
+JNK1	B-GENE
+also	O
+suppressed	O
+glucose	O
+deprivation	O
+-	O
+induced	O
+JNK1	B-GENE
+activation	O
+as	O
+well	O
+as	O
+HSP70	B-GENE
+gene	I-GENE
+expression	O
+.	O
+
+The	O
+interaction	O
+of	O
+AF	O
+-	O
+1	O
+with	O
+proteins	O
+that	O
+regulate	O
+distinct	O
+steps	O
+of	O
+transcription	O
+may	O
+provide	O
+a	O
+mechanism	O
+for	O
+synergistic	O
+activation	O
+of	O
+gene	O
+expression	O
+by	O
+AF	O
+-	O
+1	O
+.	O
+
+The	O
+role	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+signaling	O
+in	O
+activated	O
+DRA	B-GENE
+transcription	O
+.	O
+
+Ligand	O
+binding	O
+to	O
+the	O
+receptor	O
+complex	O
+leads	O
+to	O
+tyrosine	O
+phosphorylation	O
+and	O
+activation	O
+of	O
+Janus	B-GENE
+kinases	I-GENE
+(	O
+Jak	B-GENE
+)	O
+,	O
+phosphorylation	O
+of	O
+the	O
+signal	B-GENE
+transducing	I-GENE
+subunit	I-GENE
+gp130	I-GENE
+,	O
+followed	O
+by	O
+recruitment	O
+and	O
+phosphorylation	O
+of	O
+the	O
+signal	B-GENE
+transducer	I-GENE
+and	I-GENE
+activator	I-GENE
+of	I-GENE
+transcription	I-GENE
+factors	I-GENE
+STAT3	B-GENE
+and	O
+STAT1	B-GENE
+and	O
+the	O
+src	B-GENE
+homology	I-GENE
+domain	I-GENE
+(	O
+SH2	B-GENE
+)	O
+-	O
+containing	O
+protein	B-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+(	O
+SHP2	B-GENE
+)	O
+.	O
+
+Interestingly	O
+,	O
+an	O
+increase	O
+of	O
+distance	O
+per	O
+se	O
+did	O
+not	O
+have	O
+a	O
+deleterious	O
+effect	O
+on	O
+translation	O
+efficiency	O
+.	O
+
+We	O
+also	O
+mapped	O
+a	O
+3	O
+'	O
+-	O
+polyadenylation	O
+site	O
+504bp	O
+downstream	O
+of	O
+the	O
+TGA	O
+stop	O
+codon	O
+,	O
+consistent	O
+with	O
+the	O
+2	O
+.	O
+5kb	O
+transcript	O
+size	O
+.	O
+
+RBP56	B-GENE
+protein	I-GENE
+turned	O
+out	O
+to	O
+be	O
+hTAFII68	B-GENE
+which	O
+was	O
+isolated	O
+as	O
+a	O
+TATA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+associated	I-GENE
+factor	I-GENE
+(	O
+TAF	B-GENE
+)	O
+from	O
+a	O
+sub	O
+-	O
+population	O
+of	O
+TFIID	B-GENE
+complexes	I-GENE
+(	O
+Bertolotti	O
+A	O
+.	O
+,	O
+Lutz	O
+,	O
+Y	O
+.	O
+,	O
+Heard	O
+,	O
+D	O
+.	O
+J	O
+.	O
+,	O
+Chambon	O
+,	O
+P	O
+.	O
+,	O
+Tora	O
+,	O
+L	O
+.	O
+,	O
+1996	O
+.	O
+hTAFII68	B-GENE
+,	O
+a	O
+novel	O
+RNA	O
+/	O
+ssDNA	O
+-	O
+binding	O
+protein	O
+with	O
+homology	O
+to	O
+the	O
+proto	O
+-	O
+oncoproteins	O
+TLS	B-GENE
+/	O
+FUS	B-GENE
+and	O
+EWS	B-GENE
+is	O
+associated	O
+with	O
+both	O
+TFIID	B-GENE
+and	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+.	O
+
+An	O
+electrophoretic	O
+mobility	O
+shift	O
+assay	O
+was	O
+performed	O
+to	O
+characterize	O
+the	O
+binding	O
+property	O
+of	O
+TR2	B-GENE
+and	O
+its	O
+truncated	O
+isoform	O
+.	O
+
+Gel	O
+-	O
+mobility	O
+shift	O
+analysis	O
+was	O
+also	O
+performed	O
+for	O
+the	O
+CCAAT	O
+motif	O
+at	O
+-	O
+67	O
+.	O
+
+RESULTS	O
+:	O
+We	O
+identified	O
+a	O
+full	O
+-	O
+length	O
+cDNA	O
+with	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+2883	O
+bp	O
+corresponding	O
+to	O
+a	O
+predicted	O
+protein	O
+of	O
+961	O
+amino	O
+acids	O
+that	O
+shares	O
+greater	O
+than	O
+95	O
+%	O
+homology	O
+with	O
+the	O
+rat	B-GENE
+gamma	I-GENE
+-	I-GENE
+aminobutyric	I-GENE
+acid	I-GENE
+B	I-GENE
+(	I-GENE
+GABAB	I-GENE
+)	I-GENE
+receptor	I-GENE
+.	O
+
+On	O
+Day	O
+8	O
+,	O
+the	O
+CIDR	O
+-	O
+B	O
+was	O
+removed	O
+and	O
+500	O
+micrograms	O
+cloprostenol	O
+injected	O
+,	O
+IM	O
+.	O
+
+Another	O
+tentative	O
+hotspot	O
+mutation	O
+in	O
+the	O
+third	O
+patient	O
+,	O
+a	O
+frame	O
+shift	O
+caused	O
+by	O
+a	O
+G	O
+nucleotide	O
+insertion	O
+in	O
+a	O
+monotonous	O
+repeat	O
+of	O
+six	O
+Gs	O
+in	O
+HPRT	B-GENE
+exon	I-GENE
+3	I-GENE
+,	O
+has	O
+been	O
+reported	O
+previously	O
+in	O
+three	O
+other	O
+LN	O
+patients	O
+.	O
+
+SRF	B-GENE
+-	O
+deficient	O
+embryos	O
+(	O
+Srf	B-GENE
+-	O
+/	O
+-	O
+)	O
+have	O
+a	O
+severe	O
+gastrulation	O
+defect	O
+and	O
+do	O
+not	O
+develop	O
+to	O
+term	O
+.	O
+
+These	O
+characteristic	O
+structural	O
+features	O
+were	O
+used	O
+to	O
+create	O
+the	O
+abbreviation	O
+AZF1	B-GENE
+(	O
+Asparagine	B-GENE
+-	I-GENE
+rich	I-GENE
+Zinc	I-GENE
+Finger	I-GENE
+protein	I-GENE
+)	O
+.	O
+
+Over	O
+-	O
+expression	O
+of	O
+Azf1p	B-GENE
+in	O
+the	O
+yeast	O
+cell	O
+does	O
+not	O
+influence	O
+the	O
+expression	O
+level	O
+of	O
+the	O
+mitochondrial	B-GENE
+transcription	I-GENE
+factor	I-GENE
+Mtf1p	I-GENE
+,	O
+indicating	O
+that	O
+the	O
+influence	O
+of	O
+Azf1p	B-GENE
+on	O
+the	O
+suppression	O
+of	O
+the	O
+special	O
+mitochondrial	B-GENE
+RNA	I-GENE
+polymerase	I-GENE
+mutant	I-GENE
+is	O
+an	O
+indirect	O
+one	O
+.	O
+
+We	O
+have	O
+generated	O
+a	O
+computer	O
+model	O
+of	O
+the	O
+C	O
+-	O
+terminal	O
+domain	O
+of	O
+the	O
+434	O
+repressor	O
+based	O
+on	O
+the	O
+crystal	O
+structure	O
+of	O
+the	O
+homologous	B-GENE
+UmuD	I-GENE
+'	I-GENE
+protein	I-GENE
+.	O
+
+Large	O
+-	O
+scale	O
+sequencing	O
+of	O
+two	O
+regions	O
+in	O
+human	O
+chromosome	O
+7q22	O
+:	O
+analysis	O
+of	O
+650	O
+kb	O
+of	O
+genomic	O
+sequence	O
+around	O
+the	O
+EPO	B-GENE
+and	O
+CUTL1	B-GENE
+loci	I-GENE
+reveals	O
+17	O
+genes	O
+.	O
+
+Because	O
+Trp53	B-GENE
+(	O
+the	O
+mouse	B-GENE
+homolog	I-GENE
+of	I-GENE
+human	I-GENE
+TP53	I-GENE
+)	O
+is	O
+located	O
+with	O
+Tk1	B-GENE
+on	O
+chromosome	O
+11	O
+and	O
+is	O
+critical	O
+in	O
+regulating	O
+cellular	O
+responses	O
+following	O
+exposure	O
+to	O
+DNA	O
+damaging	O
+agents	O
+,	O
+we	O
+wanted	O
+to	O
+determine	O
+if	O
+these	O
+mouse	O
+lymphoma	O
+cells	O
+harbor	O
+mutations	O
+in	O
+Trp53	B-GENE
+.	O
+
+One	O
+of	O
+these	O
+fragments	O
+shows	O
+the	O
+highest	O
+amino	O
+acid	O
+sequence	O
+homology	O
+to	O
+the	O
+insect	O
+ecdysone	O
+inducible	O
+gene	B-GENE
+E75	I-GENE
+.	O
+
+The	O
+full	O
+-	O
+length	O
+N	B-GENE
+gene	I-GENE
+,	O
+encoded	O
+by	O
+open	O
+reading	O
+frame	O
+7	O
+,	O
+was	O
+cloned	O
+from	O
+the	O
+Canadian	O
+PRRS	O
+virus	O
+,	O
+PA	O
+-	O
+8	O
+.	O
+
+Based	O
+on	O
+sequence	O
+homology	O
+,	O
+the	O
+genes	O
+were	O
+identified	O
+as	O
+TEF	B-GENE
+,	O
+encoding	O
+translation	B-GENE
+elongation	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+alpha	I-GENE
+and	O
+RPS7	B-GENE
+,	O
+encoding	O
+ribosomal	O
+protein	O
+S7	B-GENE
+.	O
+
+We	O
+have	O
+previously	O
+shown	O
+that	O
+ARNO	B-GENE
+localizes	O
+to	O
+the	O
+plasma	O
+membrane	O
+in	O
+vivo	O
+and	O
+efficiently	O
+catalyzes	O
+ARF6	B-GENE
+nucleotide	O
+exchange	O
+in	O
+vitro	O
+.	O
+
+Renal	O
+pathology	O
+and	O
+long	O
+-	O
+term	O
+outcome	O
+in	O
+childhood	O
+SLE	O
+.	O
+
+Transcription	O
+factors	O
+of	O
+the	O
+Stat	B-GENE
+family	I-GENE
+are	O
+controlled	O
+by	O
+protein	O
+kinases	O
+.	O
+
+We	O
+propose	O
+that	O
+two	O
+pathways	O
+regulate	O
+Stat5	B-GENE
+serine	O
+phosphorylation	O
+,	O
+one	O
+that	O
+is	O
+prolactin	B-GENE
+-	O
+activated	O
+and	O
+PD98059	O
+-	O
+resistant	O
+and	O
+one	O
+that	O
+is	O
+constitutively	O
+active	O
+and	O
+PD98059	O
+-	O
+sensitive	O
+and	O
+preferentially	O
+targets	O
+Stat5a	B-GENE
+.	O
+
+An	O
+approximately	O
+37	O
+-	O
+kDa	O
+cytoplasmic	O
+protein	O
+is	O
+rapidly	O
+tyrosine	O
+-	O
+phosphorylated	O
+in	O
+the	O
+response	O
+of	O
+mouse	O
+BAC1	O
+.	O
+2F5	O
+macrophages	O
+to	O
+colony	B-GENE
+stimulating	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+pp37	B-GENE
+was	O
+purified	O
+from	O
+the	O
+cytosolic	O
+fraction	O
+by	O
+anti	B-GENE
+-	I-GENE
+Tyr	I-GENE
+(	I-GENE
+P	I-GENE
+)	I-GENE
+affinity	O
+chromatography	O
+,	O
+size	O
+exclusion	O
+chromatography	O
+,	O
+and	O
+C4	O
+reverse	O
+phase	O
+high	O
+pressure	O
+liquid	O
+chromatography	O
+.	O
+
+Dose	O
+of	O
+20	O
+ig	O
+were	O
+administered	O
+within	O
+a	O
+scheme	O
+from	O
+0	O
+.	O
+1	O
+to	O
+6	O
+months	O
+in	O
+order	O
+to	O
+study	O
+its	O
+immunogenicity	O
+,	O
+which	O
+was	O
+evaluated	O
+at	O
+2	O
+,	O
+7	O
+,	O
+and	O
+12	O
+months	O
+after	O
+the	O
+first	O
+dose	O
+.	O
+
+This	O
+association	O
+was	O
+independently	O
+significant	O
+for	O
+patients	O
+treated	O
+primarily	O
+(	O
+not	O
+for	O
+recurrence	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+Local	O
+control	O
+was	O
+highest	O
+with	O
+Preop	O
+in	O
+patients	O
+presenting	O
+primarily	O
+with	O
+gross	O
+disease	O
+,	O
+and	O
+with	O
+Postop	O
+in	O
+patients	O
+presenting	O
+primarily	O
+following	O
+gross	O
+total	O
+excision	O
+.	O
+
+Its	O
+interaction	O
+with	O
+RFX5	B-GENE
+and	O
+RFXAP	B-GENE
+is	O
+essential	O
+for	O
+binding	O
+of	O
+the	O
+RFX	B-GENE
+complex	I-GENE
+to	O
+MHC	B-GENE
+-	I-GENE
+II	I-GENE
+promoters	I-GENE
+.	O
+
+We	O
+have	O
+previously	O
+mapped	O
+the	O
+defect	O
+in	O
+RIIIS	O
+/	O
+J	O
+to	O
+distal	O
+mouse	O
+Chr	O
+11	O
+,	O
+distinct	O
+from	O
+the	O
+Vwf	B-GENE
+locus	I-GENE
+on	O
+Chr	O
+6	O
+.	O
+
+These	O
+data	O
+may	O
+also	O
+aid	O
+in	O
+the	O
+localization	O
+of	O
+other	O
+disease	O
+loci	O
+mapped	O
+to	O
+this	O
+region	O
+,	O
+including	O
+the	O
+gene	O
+for	O
+tricho	O
+-	O
+dento	O
+-	O
+osseous	O
+syndrome	O
+and	O
+a	O
+murine	O
+locus	O
+for	O
+susceptibility	O
+to	O
+ozone	O
+-	O
+induced	O
+acute	O
+lung	O
+injury	O
+.	O
+
+Copyright	O
+1998	O
+Academic	O
+Press	O
+.	O
+
+An	O
+open	O
+reading	O
+frame	O
+encoding	O
+a	O
+protein	O
+which	O
+shows	O
+significant	O
+similarity	O
+to	O
+invertases	B-GENE
+and	O
+resolvases	B-GENE
+was	O
+located	O
+immediately	O
+upstream	O
+of	O
+the	O
+Pac25I	B-GENE
+R	B-GENE
+-	I-GENE
+M	I-GENE
+operon	I-GENE
+.	O
+
+Identification	O
+of	O
+a	O
+new	O
+gene	O
+in	O
+the	O
+streptococcal	O
+plasmid	O
+pLS1	O
+:	O
+the	O
+rnaI	B-GENE
+gene	I-GENE
+.	O
+
+Rather	O
+,	O
+usp	B-GENE
+is	O
+required	O
+in	O
+late	O
+third	O
+instar	O
+larvae	O
+for	O
+appropriate	O
+developmental	O
+and	O
+transcriptional	O
+responses	O
+to	O
+the	O
+ecdysone	O
+pulse	O
+that	O
+triggers	O
+puparium	O
+formation	O
+.	O
+
+An	O
+intact	O
+neurovascular	O
+supply	O
+is	O
+essential	O
+for	O
+the	O
+viability	O
+of	O
+a	O
+muscle	O
+flap	O
+.	O
+
+BACKGROUND	O
+:	O
+Studies	O
+in	O
+lean	O
+men	O
+show	O
+poor	O
+regulation	O
+of	O
+energy	O
+(	O
+EB	O
+)	O
+and	O
+fat	O
+balance	O
+(	O
+FB	O
+)	O
+during	O
+manipulation	O
+of	O
+dietary	O
+ratios	O
+of	O
+fat	O
+to	O
+carbohydrate	O
+.	O
+
+Fatal	O
+apneusis	O
+was	O
+observed	O
+under	O
+following	O
+conditions	O
+:	O
+(	O
+1	O
+)	O
+Persistent	O
+apnea	O
+was	O
+produced	O
+after	O
+a	O
+single	O
+KA	O
+microinjection	O
+in	O
+one	O
+side	O
+of	O
+the	O
+VRG	O
+-	O
+Apa	O
+(	O
+5	O
+animals	O
+)	O
+.	O
+
+A	O
+comparative	O
+analysis	O
+of	O
+the	O
+reported	O
+MOCT	O
+-	O
+associated	O
+malignant	O
+melanomas	O
+emphasizes	O
+the	O
+singularity	O
+of	O
+our	O
+case	O
+in	O
+the	O
+amelanotic	O
+character	O
+of	O
+the	O
+melanoma	O
+,	O
+its	O
+lymphotropism	O
+and	O
+the	O
+coexistence	O
+of	O
+invasive	O
+squamous	O
+cell	O
+carcinoma	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+HIV	O
+-	O
+1	O
+Gag	B-GENE
+sequences	I-GENE
+can	O
+influence	O
+the	O
+viral	B-GENE
+PR	I-GENE
+-	O
+mediated	O
+processing	O
+of	O
+the	O
+MuLV	O
+TM	B-GENE
+Env	I-GENE
+protein	I-GENE
+p15	B-GENE
+(	I-GENE
+E	I-GENE
+)	I-GENE
+.	O
+
+These	O
+results	O
+demonstrate	O
+a	O
+specific	O
+association	O
+of	O
+SIV	O
+and	O
+HIV	B-GENE
+-	I-GENE
+2	I-GENE
+nef	I-GENE
+,	O
+but	O
+not	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+nef	I-GENE
+,	O
+with	O
+TCRzeta	B-GENE
+.	O
+
+Competition	O
+EMSA	O
+established	O
+that	O
+constitutively	O
+expressed	O
+nuclear	O
+proteins	O
+bound	O
+the	O
+KCS	B-GENE
+element	I-GENE
+selectively	O
+;	O
+KCS	B-GENE
+protein	I-GENE
+binding	O
+activity	O
+correlated	O
+with	O
+promoter	O
+activity	O
+in	O
+the	O
+transient	O
+transfection	O
+reporter	O
+assay	O
+.	O
+
+Mechanism	O
+of	O
+interferon	B-GENE
+action	O
+:	O
+identification	O
+of	O
+essential	O
+positions	O
+within	O
+the	O
+novel	O
+15	B-GENE
+-	I-GENE
+base	I-GENE
+-	I-GENE
+pair	I-GENE
+KCS	I-GENE
+element	I-GENE
+required	O
+for	O
+transcriptional	O
+activation	O
+of	O
+the	O
+RNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+pkr	I-GENE
+gene	I-GENE
+.	O
+
+Expression	O
+of	O
+a	O
+novel	O
+murine	B-GENE
+phospholipase	I-GENE
+D	I-GENE
+homolog	I-GENE
+coincides	O
+with	O
+late	O
+neuronal	O
+development	O
+in	O
+the	O
+forebrain	O
+.	O
+
+We	O
+detected	O
+no	O
+effect	O
+of	O
+deleting	O
+YCL024W	B-GENE
+,	O
+either	O
+alone	O
+or	O
+in	O
+combination	O
+with	O
+deletion	O
+of	O
+GIN4	B-GENE
+.	O
+
+Paralemmin	B-GENE
+is	O
+also	O
+phosphorylated	O
+,	O
+and	O
+its	O
+mRNA	O
+is	O
+differentially	O
+spliced	O
+in	O
+a	O
+tissue	O
+-	O
+specific	O
+and	O
+developmentally	O
+regulated	O
+manner	O
+.	O
+
+The	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+CBP90	B-GENE
+had	O
+no	O
+significant	O
+similarity	O
+to	O
+any	O
+other	O
+protein	O
+,	O
+but	O
+it	O
+had	O
+a	O
+proline	O
+-	O
+rich	O
+domain	O
+at	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+.	O
+
+The	O
+effect	O
+of	O
+low	O
+-	O
+profile	O
+serine	O
+substitutions	O
+in	O
+the	O
+V3	B-GENE
+loop	O
+of	O
+HIV	O
+-	O
+1	O
+gp120	B-GENE
+IIIB	I-GENE
+/	O
+LAI	B-GENE
+on	O
+the	O
+immunogenicity	O
+of	O
+the	O
+envelope	B-GENE
+protein	O
+.	O
+
+Transcription	O
+start	O
+site	O
+mapping	O
+identified	O
+the	O
+presence	O
+of	O
+an	O
+aphidicolin	O
+-	O
+sensitive	O
+late	O
+transcript	O
+arising	O
+from	O
+a	O
+TAAG	O
+motif	O
+located	O
+at	O
+-	O
+352	O
+nucleotides	O
+and	O
+an	O
+aphidicolin	O
+-	O
+insensitive	O
+early	O
+transcript	O
+originating	O
+from	O
+a	O
+TTGT	O
+motif	O
+located	O
+35	O
+nucleotides	O
+downstream	O
+to	O
+a	O
+TATA	O
+box	O
+at	O
+-	O
+312	O
+nucleotides	O
+,	O
+with	O
+respect	O
+to	O
+the	O
++	O
+1	O
+ATG	O
+of	O
+lef2	B-GENE
+.	O
+
+The	O
+human	B-GENE
+2	I-GENE
+'	I-GENE
+,	I-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+oligoadenylate	I-GENE
+(	I-GENE
+2	I-GENE
+-	I-GENE
+5A	I-GENE
+)	I-GENE
+synthetases	I-GENE
+are	O
+members	O
+of	O
+a	O
+family	O
+interferon	B-GENE
+(	O
+IFN	B-GENE
+)	O
+-	O
+inducible	O
+anti	B-GENE
+-	I-GENE
+viral	I-GENE
+proteins	I-GENE
+.	O
+
+Our	O
+findings	O
+demonstrate	O
+a	O
+dose	O
+-	O
+dependent	O
+blockade	O
+of	O
+the	O
+mechanical	O
+sensitivity	O
+caused	O
+by	O
+a	O
+mild	O
+thermal	O
+injury	O
+by	O
+both	O
+GBP	O
+and	O
+IBG	O
+.	O
+
+These	O
+striations	O
+were	O
+caused	O
+by	O
+contact	O
+between	O
+the	O
+sharp	O
+edge	O
+of	O
+the	O
+upper	O
+canine	O
+and	O
+the	O
+P3	O
+during	O
+honing	O
+(	O
+canine	O
+/	O
+premolar	O
+complex	O
+)	O
+.	O
+
+Low	O
+PbrO2	O
+readings	O
+,	O
+however	O
+,	O
+could	O
+be	O
+caused	O
+by	O
+local	O
+microhemorrhages	O
+,	O
+undetectable	O
+on	O
+CT	O
+or	O
+MRI	O
+.	O
+
+The	O
+consequences	O
+of	O
+intensive	O
+swine	O
+production	O
+on	O
+the	O
+environment	O
+and	O
+possible	O
+solutions	O
+by	O
+means	O
+of	O
+nutrition	O
+are	O
+outlined	O
+.	O
+
+This	O
+study	O
+demonstrates	O
+that	O
+alteration	O
+of	O
+CDKN2	B-GENE
+is	O
+one	O
+of	O
+the	O
+most	O
+frequent	O
+genetic	O
+abnormalities	O
+in	O
+prostate	O
+cancer	O
+and	O
+may	O
+contribute	O
+to	O
+prostate	O
+carcinogenesis	O
+.	O
+
+The	O
+pharmacokinetic	O
+parameters	O
+which	O
+helped	O
+predict	O
+these	O
+toxicities	O
+included	O
+area	O
+under	O
+the	O
+curve	O
+and	O
+peak	O
+plasma	O
+level	O
+.	O
+
+A	O
+Chinese	O
+(	O
+HK	O
+)	O
+SF	O
+-	O
+36	O
+survey	O
+form	O
+was	O
+developed	O
+by	O
+an	O
+iterative	O
+translation	O
+process	O
+.	O
+
+However	O
+,	O
+the	O
+use	O
+of	O
+cyclosporin	O
+A	O
+is	O
+associated	O
+with	O
+an	O
+increased	O
+prevalence	O
+of	O
+hypertension	O
+in	O
+kidney	O
+transplant	O
+recipients	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+determine	O
+the	O
+effects	O
+of	O
+hypercholesterolemia	O
+and	O
+atherosclerosis	O
+-	O
+induced	O
+chronic	O
+cavernosal	O
+arterial	O
+insufficiency	O
+on	O
+cavernosal	O
+smooth	O
+muscle	O
+tone	O
+,	O
+nitric	B-GENE
+oxide	I-GENE
+synthase	I-GENE
+(	O
+NOS	B-GENE
+)	O
+activity	O
+and	O
+cavernosal	O
+tissue	O
+synthesis	O
+of	O
+constrictor	O
+eicosanoids	O
+.	O
+
+Characterization	O
+of	O
+the	O
+regulatory	O
+regions	O
+of	O
+the	O
+human	B-GENE
+aromatase	I-GENE
+(	O
+P450arom	B-GENE
+)	O
+gene	O
+involved	O
+in	O
+placenta	O
+-	O
+specific	O
+expression	O
+.	O
+
+Recombinant	B-GENE
+FVIIa	I-GENE
+was	O
+stable	O
+in	O
+the	O
+infusion	O
+pump	O
+for	O
+several	O
+days	O
+at	O
+room	O
+temperature	O
+and	O
+for	O
+24	O
+h	O
+at	O
+body	O
+temperature	O
+.	O
+
+(	O
+1992	O
+)	O
+Biochemistry	O
+31	O
+,	O
+3351	O
+-	O
+3358	O
+]	O
+.	O
+
+Levels	O
+of	O
+serum	O
+IgE	B-GENE
+were	O
+measured	O
+monthly	O
+,	O
+and	O
+nasal	O
+IgE	B-GENE
+was	O
+measured	O
+at	O
+the	O
+height	O
+and	O
+end	O
+of	O
+the	O
+season	O
+.	O
+
+A	O
+mutation	O
+in	O
+the	O
+5	O
+'	O
+C2U4	O
+repeat	O
+causes	O
+underaccumulation	O
+of	O
+snR13F	B-GENE
+,	O
+whereas	O
+mutations	O
+in	O
+the	O
+3	O
+'	O
+C2U4	O
+repeat	O
+cause	O
+the	O
+accumulation	O
+of	O
+two	O
+novel	O
+RNAs	O
+that	O
+migrate	O
+in	O
+the	O
+500	O
+-	O
+nt	O
+range	O
+.	O
+
+By	O
+directly	O
+interacting	O
+with	O
+both	O
+Arfs	B-GENE
+and	O
+tyrosine	B-GENE
+kinases	I-GENE
+involved	O
+in	O
+regulating	O
+cell	O
+growth	O
+and	O
+cytoskeletal	O
+organization	O
+,	O
+ASAP1	B-GENE
+could	O
+coordinate	O
+membrane	O
+remodeling	O
+events	O
+with	O
+these	O
+processes	O
+.	O
+
+These	O
+sorting	B-GENE
+nexins	I-GENE
+also	O
+associated	O
+with	O
+the	O
+long	O
+isoform	O
+of	O
+the	O
+leptin	B-GENE
+receptor	I-GENE
+but	O
+not	O
+with	O
+the	O
+short	O
+and	O
+medium	O
+isoforms	O
+.	O
+
+Cyclophilins	B-GENE
+are	O
+cis	B-GENE
+-	I-GENE
+trans	I-GENE
+-	I-GENE
+peptidyl	I-GENE
+-	I-GENE
+prolyl	I-GENE
+isomerases	I-GENE
+that	O
+bind	O
+to	O
+and	O
+are	O
+inhibited	O
+by	O
+the	O
+immunosuppressant	O
+cyclosporin	O
+A	O
+(	O
+CsA	O
+)	O
+.	O
+
+In	O
+vitro	O
+protein	O
+retention	O
+experiments	O
+in	O
+which	O
+Hsp90	B-GENE
+heterocomplexes	I-GENE
+were	O
+precipitated	O
+resulted	O
+in	O
+coprecipitation	O
+of	O
+Cns1	B-GENE
+.	O
+
+The	O
+Ras	B-GENE
+-	I-GENE
+related	I-GENE
+GTPases	I-GENE
+are	O
+small	O
+,	O
+20	O
+-	O
+to	O
+25	O
+-	O
+kDa	O
+proteins	O
+which	O
+cycle	O
+between	O
+an	O
+inactive	O
+GDP	O
+-	O
+bound	O
+form	O
+and	O
+an	O
+active	O
+GTP	O
+-	O
+bound	O
+state	O
+.	O
+
+To	O
+modulate	O
+transcription	O
+,	O
+regulatory	O
+factors	O
+communicate	O
+with	O
+basal	O
+transcription	O
+factors	O
+and	O
+/	O
+or	O
+RNA	B-GENE
+polymerases	I-GENE
+in	O
+a	O
+variety	O
+of	O
+ways	O
+.	O
+
+Endogenous	O
+RMP	B-GENE
+was	O
+immunologically	O
+detected	O
+interacting	O
+with	O
+assembled	O
+RPB5	B-GENE
+in	O
+RNA	B-GENE
+polymerase	I-GENE
+in	O
+mammalian	O
+cells	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+rabbits	O
+were	O
+used	O
+to	O
+evaluate	O
+the	O
+sutured	O
+wound	O
+reaction	O
+with	O
+Dexon	O
+or	O
+nylon	O
+in	O
+the	O
+conjunctival	O
+flap	O
+1	O
+,	O
+4	O
+,	O
+7	O
+,	O
+14	O
+and	O
+28	O
+days	O
+after	O
+trabeculectomy	O
+surgery	O
+with	O
+or	O
+without	O
+the	O
+use	O
+of	O
+mitomycin	O
+-	O
+C	O
+.	O
+
+The	O
+mapping	O
+was	O
+completed	O
+with	O
+Southern	O
+blotting	O
+and	O
+restriction	O
+analysis	O
+.	O
+
+The	O
+zona	O
+pellucida	O
+(	O
+ZP	O
+)	O
+,	O
+the	O
+extracellular	O
+glycocalyx	O
+that	O
+surrounds	O
+the	O
+oocyte	O
+,	O
+is	O
+well	O
+known	O
+to	O
+mediate	O
+homologous	O
+gamete	O
+interaction	O
+.	O
+
+Therapeutic	O
+use	O
+of	O
+continuous	O
+subcutaneous	O
+infusion	O
+of	O
+recombinant	B-GENE
+human	I-GENE
+erythropoietin	I-GENE
+in	O
+malnourished	O
+predialysis	O
+anemic	O
+patients	O
+with	O
+diabetic	O
+nephropathy	O
+.	O
+
+Although	O
+pathological	O
+thyroid	O
+function	O
+is	O
+related	O
+to	O
+changes	O
+in	O
+energy	O
+expenditure	O
+and	O
+body	O
+composition	O
+,	O
+its	O
+possible	O
+influence	O
+on	O
+leptin	B-GENE
+levels	O
+remains	O
+to	O
+be	O
+determined	O
+.	O
+
+These	O
+cognitive	O
+deficits	O
+were	O
+prevented	O
+in	O
+animals	O
+treated	O
+with	O
+MK	O
+-	O
+801	O
+during	O
+SE	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+the	O
+mechanism	O
+of	O
+activation	O
+of	O
+HIF	B-GENE
+-	I-GENE
+1alpha	I-GENE
+is	O
+a	O
+multi	O
+-	O
+step	O
+process	O
+which	O
+includes	O
+hypoxia	O
+-	O
+dependent	O
+nuclear	O
+import	O
+and	O
+activation	O
+(	O
+derepression	O
+)	O
+of	O
+the	O
+transactivation	O
+domain	O
+,	O
+resulting	O
+in	O
+recruitment	O
+of	O
+the	O
+CREB	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+CBP	B-GENE
+)	O
+/	O
+p300	B-GENE
+coactivator	I-GENE
+.	O
+
+Thus	O
+,	O
+hypoxia	O
+-	O
+inducible	O
+nuclear	O
+import	O
+and	O
+transactivation	O
+by	O
+recruitment	O
+of	O
+CBP	B-GENE
+can	O
+be	O
+functionally	O
+separated	O
+from	O
+one	O
+another	O
+and	O
+play	O
+critical	O
+roles	O
+in	O
+signal	O
+transduction	O
+by	O
+HIF	B-GENE
+-	I-GENE
+1alpha	I-GENE
+.	O
+
+The	O
+rat	B-GENE
+aldolase	I-GENE
+C	I-GENE
+gene	I-GENE
+encodes	O
+a	O
+glycolytic	O
+enzyme	O
+strongly	O
+expressed	O
+in	O
+adult	O
+brain	O
+.	O
+
+A	O
+synergistic	O
+effect	O
+on	O
+HCK	B-GENE
+promoter	I-GENE
+activity	O
+was	O
+observed	O
+at	O
+high	O
+concentrations	O
+of	O
+Sp1	B-GENE
+.	O
+
+Quinone	O
+-	O
+binding	O
+domain	O
+and	O
+amino	O
+acid	O
+residues	O
+involved	O
+in	O
+quinone	O
+binding	O
+.	O
+
+Western	O
+analyses	O
+with	O
+antisera	O
+raised	O
+against	O
+Lu	B-GENE
+-	I-GENE
+ECAM	I-GENE
+-	I-GENE
+1	I-GENE
+peptides	I-GENE
+show	O
+that	O
+the	O
+N	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+predicted	O
+open	O
+reading	O
+frame	O
+is	O
+present	O
+only	O
+in	O
+the	O
+larger	O
+size	O
+proteins	O
+(	O
+i	O
+.	O
+e	O
+.	O
+
+Mammalian	O
+sperm	O
+motility	O
+is	O
+regulated	O
+by	O
+a	O
+cascade	O
+of	O
+cAMP	O
+-	O
+dependent	O
+protein	O
+phosphorylation	O
+events	O
+mediated	O
+by	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+show	O
+that	O
+,	O
+like	O
+BAP2	B-GENE
+,	O
+the	O
+expression	O
+of	O
+the	O
+BAP3	B-GENE
+gene	I-GENE
+in	O
+S	O
+.	O
+cerevisiae	O
+is	O
+induced	O
+by	O
+the	O
+addition	O
+of	O
+branched	O
+-	O
+chain	O
+amino	O
+acids	O
+to	O
+the	O
+medium	O
+.	O
+
+Effect	O
+of	O
+enteral	O
+nutritional	O
+products	O
+differing	O
+in	O
+carbohydrate	O
+and	O
+fat	O
+on	O
+indices	O
+of	O
+carbohydrate	O
+and	O
+lipid	O
+metabolism	O
+in	O
+patients	O
+with	O
+NIDDM	O
+.	O
+
+Low	O
+-	O
+grade	O
+gastric	O
+MALT	O
+lymphoma	O
+and	O
+helicobacter	O
+heilmannii	O
+(	O
+Gastrospirillum	O
+hominis	O
+
+These	O
+studies	O
+support	O
+the	O
+view	O
+that	O
+HMG	B-GENE
+I	I-GENE
+(	I-GENE
+Y	I-GENE
+)	I-GENE
+is	O
+an	O
+important	O
+cofactor	O
+for	O
+HLA	B-GENE
+-	I-GENE
+DRA	I-GENE
+gene	I-GENE
+activation	O
+by	O
+Oct	B-GENE
+-	I-GENE
+2A	I-GENE
+and	O
+provide	O
+insights	O
+into	O
+its	O
+mechanism	O
+of	O
+action	O
+.	O
+
+In	O
+contrast	O
+to	O
+hemodynamic	O
+and	O
+histopathological	O
+predictors	O
+of	O
+survival	O
+,	O
+vWF	B-GENE
+:	O
+Ag	O
+does	O
+not	O
+require	O
+invasive	O
+techniques	O
+to	O
+be	O
+determined	O
+.	O
+
+CONCLUSION	O
+:	O
+We	O
+were	O
+unable	O
+to	O
+identify	O
+features	O
+of	O
+disease	O
+likely	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+clinically	O
+useful	O
+response	O
+to	O
+inhaled	O
+NO	O
+therapy	O
+using	O
+the	O
+parameters	O
+studied	O
+.	O
+
+We	O
+find	O
+that	O
+BCL	B-GENE
+-	I-GENE
+6	I-GENE
+POZ	O
+domain	O
+mutations	O
+that	O
+disrupt	O
+the	O
+interaction	O
+with	O
+N	B-GENE
+-	I-GENE
+CoR	I-GENE
+and	O
+SMRT	B-GENE
+no	O
+longer	O
+repress	O
+transcription	O
+.	O
+
+Partial	O
+characterization	O
+of	O
+the	O
+active	O
+site	O
+human	B-GENE
+platelet	I-GENE
+cAMP	I-GENE
+phosphodiesterase	I-GENE
+,	O
+PDE3A	B-GENE
+,	O
+by	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+.	O
+
+This	O
+core	O
+sequence	O
+,	O
+along	O
+with	O
+additional	O
+nonspecific	O
+downstream	O
+nucleotides	O
+,	O
+is	O
+sufficient	O
+for	O
+partial	O
+suppression	O
+of	O
+spliceosome	O
+assembly	O
+and	O
+splicing	O
+of	O
+BPV	O
+-	O
+1	O
+pre	O
+-	O
+mRNAs	O
+.	O
+
+Over	O
+-	O
+expression	O
+of	O
+the	O
+cofactor	O
+p300	B-GENE
+,	O
+which	O
+functions	O
+as	O
+a	O
+coactivator	O
+of	O
+myoD	B-GENE
+-	O
+mediated	O
+transcription	O
+,	O
+alleviated	O
+repression	O
+by	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+II	I-GENE
+.	O
+
+Familial	O
+autoimmune	O
+hepatitis	O
+and	O
+C4	B-GENE
+deficiency	O
+
+Since	O
+glutathione	B-GENE
+peroxidase	I-GENE
+(	O
+GPX	B-GENE
+)	O
+and	O
+superoxide	B-GENE
+dismutase	I-GENE
+(	O
+SOD	B-GENE
+)	O
+play	O
+a	O
+significant	O
+role	O
+in	O
+erythrocyte	O
+antioxidative	O
+defence	O
+,	O
+it	O
+is	O
+very	O
+important	O
+to	O
+determine	O
+their	O
+activity	O
+in	O
+occupationally	O
+exposed	O
+workers	O
+.	O
+
+Retroviral	B-GENE
+nucleocapsid	I-GENE
+proteins	I-GENE
+(	O
+NCPs	B-GENE
+)	O
+are	O
+CCHC	B-GENE
+-	I-GENE
+type	I-GENE
+zinc	I-GENE
+finger	I-GENE
+proteins	I-GENE
+that	O
+mediate	O
+virion	O
+RNA	O
+binding	O
+activities	O
+associated	O
+with	O
+retrovirus	O
+assembly	O
+and	O
+genomic	O
+RNA	O
+encapsidation	O
+.	O
+
+The	O
+Schizosaccharomyces	B-GENE
+pombe	I-GENE
+rad1	I-GENE
++	I-GENE
+cell	I-GENE
+cycle	I-GENE
+checkpoint	I-GENE
+control	I-GENE
+gene	I-GENE
+is	O
+required	O
+for	O
+S	O
+-	O
+phase	O
+and	O
+G2	O
+/	O
+M	O
+arrest	O
+in	O
+response	O
+to	O
+both	O
+DNA	O
+damage	O
+and	O
+incomplete	O
+DNA	O
+replication	O
+.	O
+
+It	O
+is	O
+now	O
+well	O
+established	O
+that	O
+progression	O
+through	O
+the	O
+eukaryotic	O
+cell	O
+cycle	O
+is	O
+controlled	O
+by	O
+oscillations	O
+in	O
+the	O
+activity	O
+of	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+(	O
+CDKs	B-GENE
+)	O
+.	O
+
+Positive	O
+genetic	O
+selections	O
+for	O
+inhibition	O
+of	O
+cyclin	B-GENE
+/	O
+CDK	B-GENE
+function	O
+were	O
+characterized	O
+using	O
+the	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+neo	I-GENE
+and	O
+yeast	B-GENE
+LEU2	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+hematopoietic	B-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factors	I-GENE
+(	O
+CSF	B-GENE
+)	O
+have	O
+been	O
+introduced	O
+into	O
+clinical	O
+practice	O
+as	O
+additional	O
+supportive	O
+measures	O
+that	O
+can	O
+reduce	O
+the	O
+incidence	O
+of	O
+infectious	O
+complications	O
+in	O
+patients	O
+with	O
+cancer	O
+and	O
+neutropenia	O
+.	O
+
+All	O
+injections	O
+of	O
+CSF	B-GENE
+were	O
+given	O
+after	O
+the	O
+initiation	O
+of	O
+neutropenia	O
+and	O
+continued	O
+until	O
+the	O
+occurrence	O
+of	O
+an	O
+absolute	O
+neutrophil	O
+recovery	O
+.	O
+rHu	B-GENE
+GM	I-GENE
+-	I-GENE
+CSF	I-GENE
+and	O
+rHu	B-GENE
+G	I-GENE
+-	I-GENE
+CSF	I-GENE
+,	O
+administered	O
+once	O
+daily	O
+at	O
+the	O
+250	O
+microg	O
+m	O
+(	O
+-	O
+2	O
+)	O
+day	O
+(	O
+-	O
+1	O
+)	O
+and	O
+5	O
+microg	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+day	O
+(	O
+-	O
+1	O
+)	O
+level	O
+,	O
+were	O
+effective	O
+in	O
+increasing	O
+the	O
+absolute	O
+neutrophil	O
+count	O
+and	O
+neutrophil	O
+function	O
+,	O
+as	O
+measured	O
+by	O
+an	O
+automated	O
+chemiluminescence	O
+system	O
+.	O
+
+We	O
+evaluated	O
+regional	O
+right	O
+ventricular	O
+wall	O
+motion	O
+during	O
+systole	O
+in	O
+patients	O
+with	O
+surgically	O
+repaired	O
+tetralogy	O
+of	O
+Fallot	O
+(	O
+TOF	O
+)	O
+using	O
+color	O
+kinesis	O
+imaging	O
+.	O
+
+Interestingly	O
+,	O
+we	O
+find	O
+that	O
+the	O
+interaction	O
+between	O
+Tat	B-GENE
+and	O
+hCycT1	B-GENE
+requires	O
+zinc	O
+as	O
+well	O
+as	O
+essential	O
+cysteine	O
+residues	O
+in	O
+both	O
+proteins	O
+.	O
+
+During	O
+early	O
+neurogenesis	O
+,	O
+Vnd	B-GENE
+protein	I-GENE
+is	O
+restricted	O
+to	O
+ventral	O
+column	O
+neuroectoderm	O
+and	O
+neuroblasts	O
+;	O
+later	O
+it	O
+is	O
+detected	O
+in	O
+a	O
+complex	O
+pattern	O
+of	O
+neurons	O
+.	O
+
+The	O
+repression	O
+domain	O
+,	O
+and	O
+indeed	O
+the	O
+entire	O
+Cdc68	B-GENE
+protein	I-GENE
+,	O
+is	O
+highly	O
+conserved	O
+,	O
+as	O
+shown	O
+by	O
+the	O
+sequence	O
+of	O
+the	O
+Cdc68	B-GENE
+functional	I-GENE
+homolog	I-GENE
+from	O
+the	O
+yeast	O
+Kluyveromyces	O
+lactis	O
+and	O
+by	O
+database	O
+searches	O
+.	O
+
+The	O
+exodomain	O
+alone	O
+has	O
+the	O
+high	O
+affinity	O
+hormone	O
+binding	O
+site	O
+but	O
+is	O
+not	O
+capable	O
+of	O
+generating	O
+hormonal	O
+signal	O
+.	O
+
+Pyrrolidine	O
+dithiocarbamate	O
+,	O
+a	O
+potent	O
+transcriptional	O
+inhibitor	O
+of	O
+the	O
+viral	B-GENE
+LTR	I-GENE
+,	O
+abrogated	O
+the	O
+cytokine	O
+responses	O
+in	O
+both	O
+U1	O
+and	O
+ACH	O
+-	O
+2	O
+cells	O
+,	O
+suggesting	O
+a	O
+common	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+-	O
+mediated	O
+transcriptional	O
+mechanism	O
+in	O
+these	O
+cell	O
+types	O
+despite	O
+their	O
+different	O
+modes	O
+of	O
+provirus	O
+latency	O
+.	O
+
+Furthermore	O
+,	O
+synergistic	O
+activation	O
+of	O
+ERK2	B-GENE
+occurred	O
+in	O
+the	O
+absence	O
+of	O
+changes	O
+in	O
+intracellular	O
+Ca2	O
++	O
+,	O
+and	O
+was	O
+not	O
+blocked	O
+by	O
+inhibition	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+activity	O
+and	O
+represents	O
+a	O
+separate	O
+pathway	O
+by	O
+which	O
+CD19	B-GENE
+regulates	O
+B	O
+cell	O
+function	O
+.	O
+
+The	O
+retrovesical	O
+hydatid	O
+cyst	O
+is	O
+a	O
+very	O
+rare	O
+site	O
+.	O
+
+Biochemical	O
+analysis	O
+reveals	O
+that	O
+KS1	B-GENE
+is	O
+a	O
+nuclear	O
+protein	O
+containing	O
+two	O
+transcriptional	O
+repressor	O
+domains	O
+,	O
+R1	O
+and	O
+R2	O
+.	O
+
+However	O
+,	O
+the	O
+BCH	O
+group	O
+showed	O
+inferior	O
+gross	O
+motor	O
+performance	O
+on	O
+the	O
+Bruininks	O
+-	O
+Oseretsky	O
+Test	O
+of	O
+Motor	O
+Proficiency	O
+(	O
+Bruininks	O
+1978	O
+)	O
+.	O
+
+We	O
+report	O
+here	O
+that	O
+,	O
+for	O
+a	O
+constant	O
+amount	O
+of	O
+transfected	O
+DNA	O
+,	O
+the	O
+level	O
+of	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+mRNA	O
+is	O
+increased	O
+in	O
+Vpr	B-GENE
+-	O
+expressing	O
+cells	O
+using	O
+either	O
+HIV	O
+-	O
+1	O
+or	O
+a	O
+murine	O
+leukemia	B-GENE
+virus	I-GENE
+(	I-GENE
+MLV	I-GENE
+)	I-GENE
+SL3	I-GENE
+-	I-GENE
+3	I-GENE
+LTR	I-GENE
+-	O
+CAT	B-GENE
+reporter	O
+construct	O
+.	O
+
+We	O
+identified	O
+telSMN	B-GENE
+mutations	O
+in	O
+11	O
+of	O
+these	O
+unrelated	O
+SMA	O
+-	O
+like	O
+individuals	O
+who	O
+carry	O
+a	O
+single	O
+copy	O
+of	O
+telSMN	B-GENE
+:	O
+these	O
+include	O
+two	O
+frameshift	O
+mutations	O
+(	O
+800ins11	O
+and	O
+542delGT	O
+)	O
+and	O
+three	O
+missense	O
+mutations	O
+(	O
+A2G	O
+,	O
+S262I	O
+,	O
+and	O
+T274I	O
+)	O
+.	O
+
+The	O
+decrease	O
+of	O
+TNF	B-GENE
+receptors	I-GENE
+by	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+was	O
+accompanied	O
+by	O
+down	O
+-	O
+regulation	O
+of	O
+TNF	B-GENE
+-	O
+induced	O
+activities	O
+,	O
+including	O
+cytotoxicity	O
+,	O
+caspase	B-GENE
+-	I-GENE
+3	I-GENE
+activation	O
+,	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+activation	O
+,	O
+and	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+induction	O
+.	O
+
+Type	B-GENE
+2	I-GENE
+deiodinase	I-GENE
+(	O
+D2	B-GENE
+)	O
+catalyzes	O
+the	O
+5	O
+'	O
+-	O
+deiodination	O
+of	O
+thyroxine	O
+to	O
+form	O
+3	O
+,	O
+5	O
+,	O
+3	O
+'	O
+-	O
+triiodothyronine	O
+.	O
+
+We	O
+have	O
+identified	O
+two	O
+overlapping	O
+expressed	O
+sequence	O
+tag	O
+clones	O
+,	O
+which	O
+contain	O
+the	O
+missing	O
+4	O
+.	O
+4	O
+-	O
+kb	O
+3	O
+'	O
+-	O
+UTR	O
+of	O
+the	O
+human	B-GENE
+D2	I-GENE
+(	O
+hD2	B-GENE
+)	O
+cDNA	O
+.	O
+
+Biol	O
+.	O
+
+Here	O
+we	O
+have	O
+investigated	O
+the	O
+structural	O
+requirements	O
+and	O
+consequences	O
+of	O
+regulatory	O
+phosphorylation	O
+for	O
+the	O
+interaction	O
+between	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+and	O
+JNK	B-GENE
+in	O
+vivo	O
+.	O
+
+Immunolocalization	O
+of	O
+Sop1p	B-GENE
+revealed	O
+a	O
+cytoplasmic	O
+distribution	O
+and	O
+cell	O
+fractionation	O
+studies	O
+showed	O
+that	O
+a	O
+significant	O
+fraction	O
+of	O
+Sop1p	B-GENE
+was	O
+recovered	O
+in	O
+a	O
+sedimentable	O
+fraction	O
+of	O
+the	O
+cytosolic	O
+material	O
+.	O
+
+Resultant	O
+activation	O
+of	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+/	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+JNK	B-GENE
+/	O
+SAPK	B-GENE
+)	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+full	O
+-	O
+length	O
+coding	O
+cDNA	O
+sequence	O
+of	O
+the	O
+mouse	B-GENE
+homologue	I-GENE
+of	I-GENE
+MPP3	I-GENE
+.	O
+
+The	O
+method	O
+also	O
+eliminates	O
+tagging	O
+of	O
+venous	O
+spins	O
+and	O
+concern	O
+about	O
+asymmetric	O
+magnetization	O
+transfer	O
+effects	O
+.	O
+
+Consistent	O
+with	O
+this	O
+,	O
+purified	O
+Dlk	B-GENE
+phosphorylated	O
+core	O
+histones	B-GENE
+H3	I-GENE
+,	O
+H2A	B-GENE
+and	O
+H4	B-GENE
+as	O
+exogenous	O
+substrates	O
+and	O
+endogenous	O
+histone	B-GENE
+H3	I-GENE
+in	O
+kinase	O
+assays	O
+with	O
+nuclear	O
+extracts	O
+.	O
+
+Neither	O
+Ha	B-GENE
+-	I-GENE
+Ras	I-GENE
+(	O
+G12V	O
+,	O
+T35S	O
+)	O
+(	O
+Ha	B-GENE
+-	I-GENE
+RasV12S35	I-GENE
+)	O
+,	O
+which	O
+activates	O
+the	O
+Rafl	B-GENE
+signaling	O
+pathway	O
+,	O
+nor	O
+Ha	B-GENE
+-	I-GENE
+Ras	I-GENE
+(	I-GENE
+G12V	I-GENE
+,	I-GENE
+E37G	I-GENE
+)	I-GENE
+(	O
+Ha	B-GENE
+-	I-GENE
+RasV12G37	I-GENE
+)	O
+,	O
+which	O
+stimulates	O
+the	O
+RalGDS	B-GENE
+pathway	O
+,	O
+did	O
+not	O
+have	O
+significant	O
+effects	O
+on	O
+factor	O
+-	O
+withdrawal	O
+apoptosis	O
+of	O
+myeloid	O
+cells	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+novel	O
+human	B-GENE
+cyclin	I-GENE
+,	O
+cyclin	B-GENE
+E2	I-GENE
+,	O
+that	O
+contains	O
+significant	O
+homology	O
+to	O
+cyclin	B-GENE
+E	I-GENE
+.	O
+
+Initial	O
+experience	O
+with	O
+the	O
+new	O
+technology	O
+indicates	O
+that	O
+SieScape	O
+is	O
+an	O
+alternative	O
+to	O
+other	O
+methods	O
+such	O
+as	O
+CT	O
+and	O
+MRI	O
+.	O
+
+The	O
+dopamine	B-GENE
+D4	I-GENE
+receptor	I-GENE
+as	O
+well	O
+as	O
+many	O
+other	O
+catecholaminergic	B-GENE
+receptors	I-GENE
+contain	O
+several	O
+putative	O
+SH3	B-GENE
+binding	I-GENE
+domains	I-GENE
+.	O
+
+Schizosaccharomyces	O
+pombe	O
+cells	O
+respond	O
+to	O
+nutrient	O
+deprivation	O
+by	O
+altering	O
+G2	O
+/	O
+M	O
+cell	O
+size	O
+control	O
+.	O
+
+A	O
+-	O
+tracts	O
+functioned	O
+best	O
+when	O
+positioned	O
+close	O
+to	O
+the	O
+-	O
+35	O
+hexamer	O
+rather	O
+than	O
+one	O
+helical	O
+turn	O
+farther	O
+upstream	O
+,	O
+similar	O
+to	O
+the	O
+positioning	O
+optimal	O
+for	O
+UP	O
+element	O
+function	O
+.	O
+
+Pyk2	B-GENE
+phosphorylation	O
+increased	O
+upon	O
+adherence	O
+of	O
+FLG	O
+29	O
+.	O
+1	O
+cells	O
+to	O
+fibronectin	B-GENE
+and	O
+to	O
+ST2	O
+stromal	O
+cells	O
+.	O
+
+Raf	B-GENE
+is	O
+a	O
+key	O
+serine	B-GENE
+-	I-GENE
+threonine	I-GENE
+protein	I-GENE
+kinase	I-GENE
+which	O
+participates	O
+in	O
+the	O
+transmission	O
+of	O
+growth	O
+,	O
+anti	O
+-	O
+apoptotic	O
+and	O
+differentiation	O
+messages	O
+.	O
+
+The	O
+US	O
+National	O
+Institute	O
+on	O
+Alcohol	O
+Abuse	O
+and	O
+Alcoholism	O
+(	O
+NIAAA	O
+)	O
+recognizes	O
+two	O
+forms	O
+of	O
+problematic	O
+drinking	O
+:	O
+'	O
+willful	O
+alcohol	O
+abuse	O
+'	O
+,	O
+a	O
+behavioural	O
+problem	O
+,	O
+and	O
+'	O
+alcohol	O
+dependence	O
+'	O
+,	O
+a	O
+true	O
+medical	O
+disorder	O
+,	O
+which	O
+includes	O
+a	O
+genetic	O
+component	O
+,	O
+that	O
+can	O
+be	O
+scientifically	O
+understood	O
+and	O
+medically	O
+treated	O
+.	O
+
+Collagen	B-GENE
+was	O
+extracted	O
+from	O
+the	O
+skin	O
+,	O
+and	O
+the	O
+lack	O
+of	O
+type	B-GENE
+III	I-GENE
+collagen	I-GENE
+was	O
+determined	O
+by	O
+means	O
+of	O
+sodium	O
+dodecyl	O
+sulfate	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+(	O
+SDS	O
+-	O
+PAGE	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+During	O
+the	O
+7	O
+-	O
+year	O
+period	O
+,	O
+10	O
+,	O
+331	O
+symptomatic	O
+duodenal	O
+ulcer	O
+diseases	O
+were	O
+diagnosed	O
+.	O
+
+In	O
+turn	O
+,	O
+assembly	O
+of	O
+this	O
+complex	O
+mediates	O
+the	O
+enzymatic	O
+activation	O
+of	O
+the	O
+p21	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+1	I-GENE
+and	O
+facilitates	O
+actin	B-GENE
+polymerization	O
+.	O
+
+Jembrana	O
+disease	O
+virus	O
+(	O
+JDV	O
+)	O
+is	O
+a	O
+newly	O
+identified	O
+bovine	O
+lentivirus	O
+that	O
+is	O
+closely	O
+related	O
+to	O
+the	O
+bovine	O
+immunodeficiency	O
+virus	O
+(	O
+BIV	O
+)	O
+.	O
+
+Approximately	O
+50	O
+%	O
+of	O
+the	O
+residues	O
+are	O
+conserved	O
+among	O
+all	O
+three	O
+sequences	O
+,	O
+yet	O
+all	O
+three	O
+viruses	O
+have	O
+retained	O
+response	O
+elements	O
+for	O
+glucocorticoids	O
+,	O
+two	O
+positionally	O
+conserved	O
+CCAAT	O
+boxes	O
+,	O
+and	O
+positionally	O
+conserved	O
+TATA	O
+boxes	O
+.	O
+
+Nhp2p	B-GENE
+is	O
+a	O
+highly	O
+basic	O
+protein	O
+that	O
+belongs	O
+to	O
+a	O
+family	O
+of	O
+putative	O
+RNA	O
+-	O
+binding	O
+proteins	O
+.	O
+
+This	O
+survey	O
+included	O
+3000	O
+randomly	O
+selected	O
+Norwegians	O
+above	O
+18	O
+years	O
+of	O
+age	O
+who	O
+received	O
+the	O
+European	O
+Organization	O
+for	O
+Research	O
+and	O
+Treatment	O
+of	O
+Cancer	O
+Core	O
+Quality	O
+of	O
+Life	O
+Questionnaire	O
+(	O
+EORTC	O
+QLQ	O
+-	O
+C30	O
+(	O
++	O
+3	O
+)	O
+by	O
+mail	O
+.	O
+
+During	O
+presentation	O
+of	O
+happy	O
+facial	O
+expressions	O
+,	O
+we	O
+detected	O
+a	O
+signal	O
+increase	O
+predominantly	O
+in	O
+the	O
+left	O
+anterior	O
+cingulate	O
+gyrus	O
+,	O
+bilateral	O
+posterior	O
+cingulate	O
+gyri	O
+,	O
+medial	O
+frontal	O
+cortex	O
+and	O
+right	O
+supramarginal	O
+gyrus	O
+,	O
+brain	O
+regions	O
+previously	O
+implicated	O
+in	O
+visuospatial	O
+and	O
+emotion	O
+processing	O
+tasks	O
+.	O
+
+Down	O
+-	O
+regulation	O
+of	O
+IRS	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+linked	O
+to	O
+its	O
+serine	O
+phosphorylation	O
+dependent	O
+on	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+activity	O
+and	O
+appears	O
+required	O
+for	O
+differentiation	O
+to	O
+occur	O
+,	O
+as	O
+IRS	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+not	O
+modified	O
+and	O
+continues	O
+to	O
+accumulate	O
+in	O
+a	O
+nondifferentiating	O
+myoblast	O
+cell	O
+line	O
+.	O
+
+This	O
+study	O
+utilizes	O
+the	O
+mammalian	O
+two	O
+-	O
+hybrid	O
+system	O
+to	O
+examine	O
+the	O
+role	O
+of	O
+ligand	O
+in	O
+the	O
+dimerization	O
+of	O
+human	B-GENE
+progesterone	I-GENE
+receptor	I-GENE
+(	O
+hPR	B-GENE
+)	O
+.	O
+
+One	O
+of	O
+its	O
+unique	O
+features	O
+appears	O
+to	O
+be	O
+the	O
+unusually	O
+short	O
+5	O
+'	O
+-	O
+untranslated	O
+regions	O
+(	O
+UTR	O
+)	O
+(	O
+1	O
+-	O
+6	O
+nucleotides	O
+(	O
+nts	O
+)	O
+)	O
+and	O
+the	O
+apparent	O
+absence	O
+of	O
+5	O
+'	O
+-	O
+cap	O
+structures	O
+from	O
+its	O
+mRNAs	O
+.	O
+
+The	O
+gene	B-GENE
+encoding	I-GENE
+human	I-GENE
+tissue	I-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+(	O
+t	B-GENE
+-	I-GENE
+PA	I-GENE
+)	O
+is	O
+regulated	O
+in	O
+a	O
+cell	O
+-	O
+type	O
+-	O
+specific	O
+manner	O
+.	O
+
+Both	O
+the	O
+presence	O
+of	O
+arginine	O
+and	O
+anaerobiosis	O
+are	O
+needed	O
+to	O
+trigger	O
+induction	O
+of	O
+the	O
+pathway	O
+.	O
+
+Competition	O
+with	O
+a	O
+putative	O
+MADS	B-GENE
+box	I-GENE
+consensus	O
+binding	O
+site	O
+from	O
+the	O
+promoter	O
+of	O
+the	O
+coordinately	O
+regulated	O
+opaque	B-GENE
+-	I-GENE
+phase	I-GENE
+-	I-GENE
+specific	I-GENE
+gene	I-GENE
+PEP1	I-GENE
+(	O
+SAP1	B-GENE
+)	O
+and	O
+the	O
+human	B-GENE
+MADS	I-GENE
+box	I-GENE
+consensus	I-GENE
+binding	I-GENE
+site	I-GENE
+for	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+demonstrated	O
+that	O
+one	O
+of	O
+the	O
+three	O
+complexes	O
+formed	O
+was	O
+specific	O
+to	O
+the	O
+OP4	B-GENE
+sequence	I-GENE
+.	O
+
+The	O
+human	B-GENE
+SHBG	I-GENE
+proximal	I-GENE
+promoter	I-GENE
+was	O
+analyzed	O
+by	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+,	O
+and	O
+the	O
+functional	O
+significance	O
+of	O
+6	O
+footprinted	O
+regions	O
+(	O
+FP1	O
+-	O
+FP6	O
+)	O
+within	O
+the	O
+proximal	O
+promoter	O
+was	O
+studied	O
+in	O
+human	O
+HepG2	O
+hepatoblastoma	O
+cells	O
+.	O
+
+In	O
+vitro	O
+translation	O
+and	O
+in	O
+vivo	O
+polysome	O
+profile	O
+analysis	O
+indicated	O
+that	O
+transcripts	B-GENE
+C	I-GENE
+and	I-GENE
+E	I-GENE
+were	O
+translated	O
+with	O
+similar	O
+translational	O
+efficiencies	O
+that	O
+are	O
+substantially	O
+greater	O
+than	O
+that	O
+of	O
+transcript	B-GENE
+D	I-GENE
+,	O
+suggesting	O
+that	O
+5	O
+'	O
+-	O
+untranslated	O
+regions	O
+play	O
+a	O
+role	O
+in	O
+translational	O
+control	O
+.	O
+
+We	O
+have	O
+introduced	O
+a	O
+mutation	O
+(	O
+Ser36	O
+-	O
+-	O
+>	O
+Asn	O
+)	O
+into	O
+this	O
+domain	O
+of	O
+p190	B-GENE
+that	O
+decreased	O
+its	O
+ability	O
+to	O
+bind	O
+guanine	O
+nucleotide	O
+when	O
+expressed	O
+as	O
+a	O
+hemagglutinin	B-GENE
+(	O
+HA	B-GENE
+)	O
+-	O
+tagged	O
+protein	O
+in	O
+COS	O
+cells	O
+.	O
+
+Wild	O
+type	O
+HA	B-GENE
+-	O
+p190	B-GENE
+induced	O
+a	O
+phenotype	O
+of	O
+rounded	O
+cells	O
+with	O
+long	O
+,	O
+beaded	O
+extensions	O
+similar	O
+to	O
+that	O
+seen	O
+when	O
+Rho	B-GENE
+function	O
+is	O
+disrupted	O
+by	O
+ADP	O
+-	O
+ribosylation	O
+.	O
+
+We	O
+emphasize	O
+that	O
+ANCA	B-GENE
+-	O
+associated	O
+vasculitis	O
+is	O
+another	O
+important	O
+complication	O
+of	O
+RA	O
+.	O
+
+The	O
+downstream	O
+,	O
+TATA	O
+-	O
+less	O
+promoter	O
+has	O
+high	O
+G	O
++	O
+C	O
+content	O
+,	O
+and	O
+exon	O
+1b	O
+predominates	O
+among	O
+abundantly	O
+expressed	O
+mRNA	O
+species	O
+.	O
+
+Although	O
+we	O
+predicted	O
+that	O
+overexpression	O
+of	O
+the	O
+COOH	O
+-	O
+terminal	O
+domains	O
+,	O
+which	O
+were	O
+thought	O
+to	O
+be	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+SREBP	B-GENE
+processing	O
+,	O
+would	O
+result	O
+in	O
+disruption	O
+of	O
+the	O
+SREBP	B-GENE
+-	O
+dependent	O
+transcriptional	O
+regulation	O
+of	O
+several	O
+genes	O
+,	O
+the	O
+mRNA	O
+levels	O
+for	O
+3	B-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+3	I-GENE
+-	I-GENE
+methylglutaryl	I-GENE
+coenzyme	I-GENE
+A	I-GENE
+(	I-GENE
+HMG	I-GENE
+CoA	I-GENE
+)	I-GENE
+synthase	I-GENE
+in	O
+these	O
+two	O
+cell	O
+lines	O
+were	O
+regulated	O
+in	O
+a	O
+sterol	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Dry	O
+matter	O
+intake	O
+,	O
+apparent	O
+nutrient	O
+digestibilities	O
+,	O
+serum	O
+chemistry	O
+profiles	O
+,	O
+sphingolipid	O
+concentrations	O
+,	O
+and	O
+persistency	O
+of	O
+FB1	O
+in	O
+tissues	O
+were	O
+evaluated	O
+.	O
+
+However	O
+,	O
+no	O
+studies	O
+have	O
+been	O
+conducted	O
+to	O
+further	O
+investigate	O
+this	O
+potentially	O
+hazardous	O
+effect	O
+of	O
+lidocaine	O
+.	O
+
+E	O
+.	O
+,	O
+Scott	O
+,	O
+J	O
+.	O
+
+Yap1p	B-GENE
+is	O
+constitutively	O
+nuclear	O
+in	O
+a	O
+crm1	B-GENE
+mutant	I-GENE
+,	O
+and	O
+Crm1p	B-GENE
+binds	O
+to	O
+a	O
+nuclear	O
+export	O
+sequence	O
+(	O
+NES	O
+)	O
+-	O
+like	O
+sequence	O
+in	O
+Yap1p	B-GENE
+in	O
+the	O
+presence	O
+of	O
+RanGTP	B-GENE
+.	O
+
+Mean	O
+intake	O
+of	O
+vitamin	O
+A	O
+amounted	O
+to	O
+1	O
+.	O
+1	O
+and	O
+0	O
+.	O
+9	O
+mg	O
+RE	O
+/	O
+day	O
+for	O
+men	O
+and	O
+women	O
+,	O
+respectively	O
+;	O
+the	O
+contributions	O
+of	O
+meat	O
+,	O
+fats	O
+and	O
+oils	O
+,	O
+vegetables	O
+and	O
+dairy	O
+products	O
+to	O
+total	O
+intake	O
+were	O
+35	O
+%	O
+,	O
+24	O
+%	O
+,	O
+16	O
+%	O
+,	O
+and	O
+16	O
+%	O
+,	O
+respectively	O
+.	O
+
+Furthermore	O
+,	O
+RING1	B-GENE
+overexpression	O
+results	O
+in	O
+enhanced	O
+expression	O
+of	O
+the	O
+proto	O
+-	O
+oncogenes	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+.	O
+
+The	O
+yeast	B-GENE
+RER2	I-GENE
+gene	I-GENE
+,	O
+identified	O
+by	O
+endoplasmic	O
+reticulum	O
+protein	O
+localization	O
+mutations	O
+,	O
+encodes	O
+cis	B-GENE
+-	I-GENE
+prenyltransferase	I-GENE
+,	O
+a	O
+key	O
+enzyme	O
+in	O
+dolichol	O
+synthesis	O
+.	O
+
+The	O
+yeast	O
+retrotransposon	B-GENE
+Ty5	I-GENE
+preferentially	O
+integrates	O
+into	O
+regions	O
+of	O
+silent	O
+chromatin	O
+.	O
+
+The	O
+loss	O
+of	O
+SKO1	B-GENE
+completely	O
+restored	O
+ENA1	B-GENE
+expression	O
+in	O
+a	O
+hog1	B-GENE
+mutant	I-GENE
+and	O
+partially	O
+suppressed	O
+the	O
+osmotic	O
+stress	O
+sensitivity	O
+,	O
+qualifying	O
+Sko1p	B-GENE
+as	O
+a	O
+downstream	O
+effector	O
+of	O
+the	O
+HOG	B-GENE
+pathway	O
+.	O
+
+Elevated	O
+expression	O
+of	O
+a	O
+previously	O
+uncharacterized	O
+gene	O
+,	O
+SPP381	B-GENE
+,	O
+efficiently	O
+suppresses	O
+the	O
+growth	O
+and	O
+splicing	O
+defects	O
+of	O
+a	O
+temperature	O
+-	O
+sensitive	O
+(	O
+Ts	O
+)	O
+mutant	B-GENE
+prp38	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+The	O
+slower	O
+-	O
+electrophoretic	O
+-	O
+mobility	O
+form	O
+of	O
+p68	B-GENE
+was	O
+absent	O
+in	O
+human	O
+cells	O
+in	O
+G1	O
+/	O
+S	O
+and	O
+appeared	O
+as	O
+the	O
+cells	O
+entered	O
+G2	O
+/	O
+M	O
+.	O
+
+We	O
+have	O
+identified	O
+amino	O
+acid	O
+sequences	O
+in	O
+mammalian	O
+and	O
+Xenopus	O
+NeuroD1	B-GENE
+/	O
+BETA2	B-GENE
+that	O
+are	O
+necessary	O
+for	O
+insulin	B-GENE
+gene	I-GENE
+expression	O
+and	O
+ectopic	O
+neurogenesis	O
+.	O
+
+Recent	O
+studies	O
+have	O
+suggested	O
+that	O
+Y319	O
+also	O
+positively	O
+regulate	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+function	O
+.	O
+
+Genetic	O
+and	O
+molecular	O
+data	O
+indicate	O
+that	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+Pan	I-GENE
+and	O
+CiD	B-GENE
+compete	O
+for	O
+binding	O
+to	O
+Arm	B-GENE
+,	O
+leading	O
+to	O
+a	O
+compromised	O
+transduction	O
+of	O
+the	O
+Wg	B-GENE
+signal	O
+in	O
+heterozygous	O
+ciD	B-GENE
+/	I-GENE
++	I-GENE
+animals	O
+and	O
+to	O
+a	O
+dramatic	O
+enhancement	O
+of	O
+the	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+activity	O
+of	O
+CiD	B-GENE
+in	O
+homozygous	O
+mutants	O
+.	O
+
+Another	O
+ORF	O
+,	O
+dda	B-GENE
+.	I-GENE
+2	I-GENE
+located	O
+between	O
+modA	B-GENE
+and	O
+dda	B-GENE
+,	O
+shares	O
+sequence	O
+similarity	O
+with	O
+sigma70	B-GENE
+,	O
+and	O
+we	O
+call	O
+it	O
+srd	B-GENE
+.	O
+
+The	O
+location	O
+of	O
+the	O
+IBS	O
+within	O
+the	O
+catB	B-GENE
+structural	I-GENE
+gene	I-GENE
+,	O
+the	O
+cooperativity	O
+observed	O
+in	O
+footprinting	O
+studies	O
+and	O
+phasing	O
+studies	O
+suggest	O
+that	O
+the	O
+IBS	O
+participates	O
+in	O
+the	O
+interaction	O
+of	O
+CatR	B-GENE
+with	O
+the	O
+upstream	O
+binding	O
+sites	O
+by	O
+looping	O
+out	O
+the	O
+intervening	O
+DNA	O
+.	O
+
+In	O
+vitro	O
+transcription	O
+assays	O
+demonstrate	O
+that	O
+the	O
+TCA	O
+-	O
+cycle	O
+intermediate	O
+,	O
+fumarate	O
+,	O
+directly	O
+and	O
+specifically	O
+inhibits	O
+the	O
+formation	O
+of	O
+the	O
+clcA	B-GENE
+transcript	I-GENE
+.	O
+
+BIAcore	O
+analysis	O
+gave	O
+a	O
+Kaff	O
+of	O
+4	O
+.	O
+4	O
+x	O
+10	O
+(	O
+10	O
+)	O
+M	O
+-	O
+1	O
+for	O
+the	O
+binding	O
+of	O
+N	B-GENE
+-	I-GENE
+A3	I-GENE
+to	O
+T84	B-GENE
+.	I-GENE
+1	I-GENE
+and	O
+2	O
+.	O
+2	O
+x	O
+10	O
+(	O
+10	O
+)	O
+M	O
+-	O
+1	O
+for	O
+the	O
+binding	O
+of	O
+N	B-GENE
+-	I-GENE
+A3	I-GENE
+to	O
+T84	B-GENE
+.	I-GENE
+66	I-GENE
+.	O
+
+Expression	O
+of	O
+p130	B-GENE
+(	O
+Cas	B-GENE
+)	O
+(	O
+Cas	B-GENE
+)	O
+,	O
+a	O
+major	O
+binding	O
+protein	O
+for	O
+the	O
+Crk	B-GENE
+SH2	B-GENE
+-	I-GENE
+domain	I-GENE
+,	O
+also	O
+induced	O
+JNK	B-GENE
+activation	O
+,	O
+which	O
+was	O
+blocked	O
+by	O
+the	O
+SH2	B-GENE
+-	I-GENE
+mutant	I-GENE
+of	O
+Crk	B-GENE
+.	O
+
+Positive	O
+correlations	O
+were	O
+seen	O
+between	O
+the	O
+measurements	O
+for	O
+protein	O
+intake	O
+(	O
+r	O
+=	O
+.	O
+58	O
+,	O
+P	O
+=	O
+.	O
+0026	O
+)	O
+energy	O
+intake	O
+(	O
+r	O
+=	O
+.	O
+78	O
+,	O
+P	O
+<	O
+.	O
+00001	O
+)	O
+,	O
+with	O
+mean	O
+differences	O
+of	O
+.	O
+066	O
+g	O
+/	O
+kg	O
+/	O
+d	O
+(	O
+SD	O
+.	O
+38	O
+)	O
+2	O
+.	O
+04	O
+kcal	O
+/	O
+kg	O
+/	O
+day	O
+(	O
+SD	O
+6	O
+.	O
+67	O
+)	O
+,	O
+respectively	O
+.	O
+
+The	O
+Og4C3	B-GENE
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+(	O
+ELISA	O
+)	O
+to	O
+detect	O
+circulating	O
+Wuchereria	B-GENE
+bancrofti	I-GENE
+antigen	I-GENE
+uses	O
+50	O
+microL	O
+of	O
+serum	O
+.	O
+
+We	O
+now	O
+show	O
+that	O
+gp200	B-GENE
+-	O
+MR6	B-GENE
+ligation	O
+can	O
+also	O
+mimic	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+and	O
+have	O
+an	O
+anti	O
+-	O
+proliferative	O
+pro	O
+-	O
+maturational	O
+influence	O
+within	O
+the	O
+immune	O
+system	O
+,	O
+causing	O
+up	O
+-	O
+regulation	O
+of	O
+co	O
+-	O
+stimulatory	O
+molecules	O
+on	O
+B	O
+lymphocytes	O
+.	O
+
+The	O
+Mig1	B-GENE
+repressor	I-GENE
+is	O
+a	O
+zinc	B-GENE
+finger	I-GENE
+protein	I-GENE
+that	O
+mediates	O
+glucose	O
+repression	O
+in	O
+yeast	O
+.	O
+
+Recurrent	O
+arterial	O
+thrombotic	O
+disease	O
+on	O
+young	O
+onset	O
+and	O
+protein	B-GENE
+S	I-GENE
+deficiency	O
+.	O
+
+We	O
+showed	O
+that	O
+Stat3	B-GENE
+and	O
+Stat3beta	B-GENE
+were	O
+affinity	O
+purified	O
+using	O
+phosphopeptides	O
+containing	O
+Y704	O
+and	O
+Y744	O
+but	O
+not	O
+by	O
+nonphosphorylated	O
+peptide	O
+analogues	O
+or	O
+by	O
+phosphopeptides	O
+containing	O
+Y729	O
+and	O
+Y764	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+results	O
+indicate	O
+that	O
+the	O
+FCR1	B-GENE
+gene	I-GENE
+behaves	O
+as	O
+a	O
+negative	O
+regulator	O
+of	O
+drug	O
+resistance	O
+in	O
+C	O
+.	O
+albicans	O
+and	O
+constitute	O
+the	O
+first	O
+evidence	O
+that	O
+FCZ	O
+resistance	O
+can	O
+result	O
+from	O
+the	O
+inactivation	O
+of	O
+a	O
+regulatory	O
+factor	O
+such	O
+as	O
+Fcr1p	B-GENE
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+late	O
+MYO	O
+/	O
+M	O
+is	O
+more	O
+useful	O
+than	O
+washout	O
+rate	O
+to	O
+assess	O
+the	O
+effect	O
+of	O
+treatment	O
+on	O
+heart	O
+failure	O
+due	O
+to	O
+DCM	O
+.	O
+
+This	O
+study	O
+was	O
+undertaken	O
+to	O
+evaluate	O
+how	O
+couplers	O
+and	O
+their	O
+placement	O
+affect	O
+the	O
+ALGO2	O
+click	O
+spectral	O
+properties	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Pretreatment	O
+with	O
+OCs	O
+prior	O
+to	O
+pituitary	O
+suppression	O
+in	O
+the	O
+early	O
+follicular	O
+phase	O
+decreases	O
+ovarian	O
+cyst	O
+formation	O
+,	O
+without	O
+an	O
+apparent	O
+effect	O
+on	O
+subsequent	O
+follicular	O
+recruitment	O
+or	O
+pregnancy	O
+rates	O
+.	O
+
+With	O
+regard	O
+to	O
+the	O
+optimal	O
+threshold	O
+values	O
+,	O
+sensitivity	O
+and	O
+specificity	O
+were	O
+100	O
+%	O
+/	O
+97	O
+%	O
+and	O
+95	O
+%	O
+/	O
+95	O
+%	O
+with	O
+FDG	O
+PET	O
+,	O
+compared	O
+to	O
+86	O
+%	O
+/	O
+92	O
+%	O
+and	O
+77	O
+%	O
+/	O
+82	O
+%	O
+with	O
+IS	O
+,	O
+respectively	O
+.	O
+
+Dorsal	O
+root	O
+ganglia	O
+neuron	O
+-	O
+specific	O
+promoter	O
+activity	O
+of	O
+the	O
+rabbit	B-GENE
+beta	I-GENE
+-	I-GENE
+galactoside	I-GENE
+alpha1	I-GENE
+,	I-GENE
+2	I-GENE
+-	I-GENE
+fucosyltransferase	I-GENE
+gene	I-GENE
+.	O
+
+This	O
+suggests	O
+roles	O
+for	O
+both	O
+the	O
+CE1	O
+and	O
+CE2	O
+elements	O
+in	O
+regulating	O
+Hoxb1	B-GENE
+gene	I-GENE
+expression	O
+during	O
+development	O
+.	O
+
+CAL	O
+gain	O
+amounted	O
+to	O
+4	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+mm	O
+,	O
+60	O
+%	O
+of	O
+the	O
+defects	O
+showing	O
+CAL	O
+gain	O
+>	O
+or	O
+=	O
+4	O
+mm	O
+.	O
+
+Lead	O
+fixation	O
+in	O
+dogs	O
+achieved	O
+with	O
+RF	O
+energy	O
+.	O
+
+Further	O
+,	O
+we	O
+show	O
+that	O
+this	O
+EIA	B-GENE
+-	O
+inducible	O
+CBF	O
+/	O
+cdc2	B-GENE
+is	O
+related	O
+to	O
+the	O
+CBF	B-GENE
+which	O
+was	O
+shown	O
+to	O
+activate	O
+the	O
+heat	B-GENE
+shock	I-GENE
+protein	I-GENE
+70	I-GENE
+promoter	I-GENE
+.	O
+
+The	O
+percutaneous	O
+absorption	O
+of	O
+clindamycin	O
+was	O
+studied	O
+in	O
+healthy	O
+male	O
+volunteers	O
+,	O
+comparing	O
+two	O
+investigative	O
+clindamycin	O
+(	O
+%	O
+w	O
+/	O
+v	O
+)	O
+/	O
+tretinoin	O
+(	O
+0	O
+.	O
+025	O
+%	O
+w	O
+/	O
+v	O
+)	O
+gels	O
+,	O
+containing	O
+clindamycin	O
+phosphate	O
+ester	O
+and	O
+clindamycin	O
+HCl	O
+,	O
+respectively	O
+,	O
+relative	O
+to	O
+a	O
+clindamycin	O
+phosphate	O
+lotion	O
+(	O
+1	O
+%	O
+clindamycin	O
+;	O
+Dalacin	O
+T	O
+)	O
+.	O
+
+The	O
+BAL	O
+concentrations	O
+of	O
+the	O
+nine	O
+cytokines	O
+evaluated	O
+for	O
+the	O
+more	O
+and	O
+less	O
+affected	O
+lungs	O
+were	O
+compared	O
+:	O
+interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+)	O
+,	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+,	O
+IL	B-GENE
+-	I-GENE
+12	I-GENE
+,	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+,	O
+and	O
+interferon	B-GENE
+gamma	I-GENE
+(	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+)	O
+showed	O
+significant	O
+differences	O
+(	O
+p	O
+ranged	O
+between	O
+0	O
+.	O
+
+Phosphorylation	O
+analyses	O
+indicated	O
+that	O
+inhibition	O
+of	O
+ERK	B-GENE
+-	I-GENE
+1	I-GENE
+/	I-GENE
+2	I-GENE
+decreased	O
+okadaic	O
+acid	O
+-	O
+elevated	O
+phosphorylation	O
+of	O
+JunD	B-GENE
+and	O
+FosB	B-GENE
+.	O
+
+Two	O
+-	O
+way	O
+analysis	O
+of	O
+variance	O
+was	O
+used	O
+to	O
+determine	O
+whether	O
+composite	O
+knowledge	O
+score	O
+differed	O
+among	O
+patient	O
+groups	O
+.	O
+
+The	O
+human	O
+pathogenic	O
+bacterium	O
+group	O
+A	O
+Streptococcus	O
+produces	O
+an	O
+extracellular	O
+cysteine	B-GENE
+protease	I-GENE
+[	O
+streptococcal	B-GENE
+pyrogenic	I-GENE
+exotoxin	I-GENE
+B	I-GENE
+(	O
+SpeB	B-GENE
+)	O
+]	O
+that	O
+is	O
+a	O
+critical	O
+virulence	O
+factor	O
+for	O
+invasive	O
+disease	O
+episodes	O
+.	O
+
+The	O
+orbitofrontal	O
+,	O
+cingulate	O
+,	O
+and	O
+anteromedial	O
+part	O
+of	O
+the	O
+dorsal	O
+premotor	O
+areas	O
+were	O
+preferentially	O
+activated	O
+by	O
+the	O
+self	O
+-	O
+initiated	O
+hand	O
+movement	O
+task	O
+(	O
+SELF	O
+)	O
+.	O
+
+The	O
+peroxisome	O
+biogenesis	O
+disorders	O
+(	O
+PBDs	O
+)	O
+are	O
+a	O
+set	O
+of	O
+lethal	O
+genetic	O
+diseases	O
+characterized	O
+by	O
+peroxisomal	O
+metabolic	O
+deficiencies	O
+,	O
+multisystem	O
+abnormalities	O
+,	O
+mental	O
+retardation	O
+,	O
+and	O
+premature	O
+death	O
+.	O
+
+The	O
+active	O
+site	O
+includes	O
+the	O
+acidic	O
+triad	O
+Asp53	O
+(	O
+the	O
+site	O
+of	O
+phosphorylation	O
+)	O
+,	O
+Asp10	O
+and	O
+Glu9	O
+.	O
+
+In	O
+PAV	O
+-	O
+3	O
+,	O
+the	O
+E1A	B-GENE
+region	I-GENE
+is	O
+located	O
+between	O
+1	O
+.	O
+5	O
+and	O
+3	O
+.	O
+8	O
+map	O
+units	O
+.	O
+
+Six	O
+putative	O
+MDV	O
+genome	O
+products	O
+,	O
+including	O
+one	O
+Rep	B-GENE
+and	O
+five	O
+non	O
+-	O
+Rep	B-GENE
+proteins	O
+,	O
+show	O
+high	O
+(	O
+70	O
+.	O
+4	O
+-	O
+90	O
+.	O
+9	O
+%	O
+)	O
+amino	O
+acid	O
+identity	O
+to	O
+the	O
+corresponding	O
+six	O
+FBNYV	B-GENE
+proteins	I-GENE
+,	O
+whereas	O
+two	O
+other	O
+Rep	B-GENE
+proteins	I-GENE
+encoded	O
+by	O
+MDV	B-GENE
+-	I-GENE
+C2	I-GENE
+and	O
+C3	B-GENE
+are	O
+82	O
+.	O
+3	O
+%	O
+and	O
+73	O
+.	O
+0	O
+%	O
+identical	O
+to	O
+those	O
+encoded	O
+by	O
+SCSV	B-GENE
+-	I-GENE
+C2	I-GENE
+and	O
+C6	B-GENE
+,	O
+respectively	O
+.	O
+
+MPO	B-GENE
+was	O
+labeled	O
+with	O
+1	O
+mCi	O
+125I	O
+by	O
+a	O
+technique	O
+of	O
+self	O
+-	O
+labeling	O
+in	O
+the	O
+presence	O
+of	O
+10	O
+(	O
+-	O
+4	O
+)	O
+M	O
+hydrogen	O
+peroxide	O
+.	O
+
+It	O
+is	O
+related	O
+to	O
+a	O
+variety	O
+of	O
+mammalian	O
+Golgi	O
+-	O
+associated	O
+proteins	O
+and	O
+to	O
+the	O
+yeast	O
+Uso1p	B-GENE
+,	O
+an	O
+essential	O
+protein	O
+involved	O
+in	O
+docking	O
+of	O
+endoplasmic	O
+reticulum	O
+-	O
+derived	O
+vesicles	O
+to	O
+the	O
+cis	O
+-	O
+Golgi	O
+.	O
+
+The	O
+data	O
+indicate	O
+that	O
+Bmp2	B-GENE
+is	O
+directly	O
+regulated	O
+by	O
+retinoic	O
+acid	O
+-	O
+bound	O
+receptors	O
+and	O
+Sp1	B-GENE
+.	O
+
+Both	O
+proteins	O
+were	O
+shown	O
+to	O
+be	O
+constitutively	O
+associated	O
+with	O
+tubulin	B-GENE
+.	O
+
+HEED	B-GENE
+was	O
+found	O
+to	O
+bind	O
+to	O
+MA	B-GENE
+protein	I-GENE
+in	O
+vitro	O
+,	O
+as	O
+efficiently	O
+as	O
+in	O
+vivo	O
+in	O
+yeast	O
+cells	O
+.	O
+
+Fas	B-GENE
+-	O
+resistant	O
+DT	O
+-	O
+40	O
+lymphoma	O
+B	O
+-	O
+cells	O
+rendered	O
+BTK	B-GENE
+-	O
+deficient	O
+through	O
+targeted	O
+disruption	O
+of	O
+the	O
+btk	B-GENE
+gene	I-GENE
+by	O
+homologous	O
+recombination	O
+knockout	O
+underwent	O
+apoptosis	O
+after	O
+Fas	B-GENE
+ligation	O
+,	O
+but	O
+wild	O
+-	O
+type	O
+DT	O
+-	O
+40	O
+cells	O
+or	O
+BTK	B-GENE
+-	O
+deficient	O
+DT	O
+-	O
+40	O
+cells	O
+reconstituted	O
+with	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+human	I-GENE
+btk	I-GENE
+gene	I-GENE
+did	O
+not	O
+.	O
+
+Varicella	B-GENE
+-	I-GENE
+zoster	I-GENE
+virus	I-GENE
+(	I-GENE
+VZV	I-GENE
+)	I-GENE
+glycoprotein	I-GENE
+gI	I-GENE
+is	O
+a	O
+type	B-GENE
+1	I-GENE
+transmembrane	I-GENE
+glycoprotein	I-GENE
+which	O
+is	O
+one	O
+component	O
+of	O
+the	O
+heterodimeric	O
+gE	B-GENE
+:	O
+gI	B-GENE
+Fc	I-GENE
+receptor	I-GENE
+complex	O
+.	O
+
+To	O
+this	O
+end	O
+,	O
+we	O
+analyzed	O
+the	O
+phosphorylation	O
+status	O
+of	O
+a	O
+universal	O
+tyrosine	B-GENE
+kinase	I-GENE
+substrate	O
+,	O
+the	O
+transforming	O
+Shc	B-GENE
+adapter	I-GENE
+protein	I-GENE
+,	O
+in	O
+fibroblasts	O
+expressing	O
+the	O
+viral	O
+oncogene	O
+.	O
+
+These	O
+genes	O
+were	O
+expressed	O
+in	O
+a	O
+Saccharomyces	O
+cerevisiae	O
+mutant	O
+in	O
+which	O
+the	O
+endogenous	B-GENE
+ferrochelatase	I-GENE
+gene	I-GENE
+(	O
+HEM15	B-GENE
+)	O
+had	O
+been	O
+deleted	O
+,	O
+and	O
+the	O
+phenotypes	O
+of	O
+the	O
+transformants	O
+were	O
+characterized	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+evidence	O
+is	O
+presented	O
+that	O
+temporally	O
+and	O
+spatially	O
+specific	O
+mef2	B-GENE
+expression	O
+is	O
+controlled	O
+by	O
+a	O
+complex	O
+array	O
+of	O
+cis	O
+-	O
+acting	O
+regulatory	O
+modules	O
+that	O
+are	O
+responsive	O
+to	O
+different	O
+genetic	O
+signals	O
+.	O
+
+Furthermore	O
+,	O
+using	O
+transgenic	O
+mouse	O
+technology	O
+we	O
+localized	O
+independent	O
+cis	O
+-	O
+regulatory	O
+elements	O
+controlling	O
+the	O
+tissue	O
+-	O
+specific	O
+expression	O
+of	O
+Pax6	B-GENE
+.	O
+
+In	O
+the	O
+second	O
+experiment	O
+,	O
+a	O
+stable	O
+nickel	O
+isotope	O
+,	O
+61Ni	O
+,	O
+was	O
+given	O
+in	O
+drinking	O
+water	O
+to	O
+20	O
+nickel	O
+-	O
+sensitized	O
+women	O
+and	O
+20	O
+age	O
+-	O
+matched	O
+controls	O
+,	O
+both	O
+groups	O
+having	O
+vesicular	O
+hand	O
+eczema	O
+of	O
+the	O
+pompholyx	O
+type	O
+.	O
+
+Folded	O
+tissue	O
+and	O
+crimped	O
+collagen	B-GENE
+fibers	O
+in	O
+the	O
+tunica	O
+albuginea	O
+permit	O
+its	O
+expansion	O
+during	O
+erection	O
+.	O
+
+Number	O
+of	O
+patients	O
+infected	O
+with	O
+nontuberculous	O
+mycobacteria	O
+(	O
+NTM	O
+)	O
+is	O
+increasing	O
+world	O
+-	O
+wide	O
+in	O
+recent	O
+years	O
+.	O
+
+Comparison	O
+of	O
+the	O
+sequences	O
+of	O
+attP	B-GENE
+,	O
+attB	B-GENE
+and	O
+bacteria	O
+-	O
+prophage	O
+junctions	O
+attL	B-GENE
+and	O
+attR	B-GENE
+showed	O
+a	O
+26	O
+bp	O
+common	O
+core	O
+sequence	O
+,	O
+where	O
+recombination	O
+takes	O
+place	O
+,	O
+near	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+integrase	B-GENE
+gene	I-GENE
+.	O
+
+Interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+treatment	O
+of	O
+posttransplant	O
+lymphoproliferative	O
+disorder	O
+in	O
+recipients	O
+of	O
+solid	O
+organ	O
+transplants	O
+.	O
+
+Immunological	O
+testing	O
+was	O
+performed	O
+on	O
+all	O
+brewery	O
+workers	O
+and	O
+some	O
+control	O
+volunteers	O
+using	O
+skin	O
+prick	O
+testing	O
+with	O
+hops	O
+,	O
+barley	O
+,	O
+and	O
+yeast	O
+antigens	O
+as	O
+well	O
+as	O
+other	O
+nonoccupational	O
+allergens	O
+,	O
+and	O
+by	O
+determining	O
+total	O
+serum	B-GENE
+IgE	I-GENE
+levels	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+evaluate	O
+the	O
+accuracy	O
+of	O
+working	O
+casts	O
+for	O
+crown	O
+and	O
+bridge	O
+restorations	O
+made	O
+from	O
+twin	O
+mix	O
+putty	O
+/	O
+wash	O
+silicone	O
+elastomeric	O
+impression	O
+materials	O
+using	O
+different	O
+types	O
+of	O
+stock	O
+tray	O
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+assess	O
+the	O
+ability	O
+of	O
+pretreatment	O
+and	O
+post	O
+-	O
+treatment	O
+prostate	B-GENE
+-	I-GENE
+specific	I-GENE
+antigen	I-GENE
+(	O
+PSA	B-GENE
+)	O
+measurements	O
+,	O
+clinical	O
+tumor	O
+stage	O
+,	O
+tumor	O
+grade	O
+,	O
+Gleason	O
+sum	O
+,	O
+race	O
+,	O
+age	O
+,	O
+and	O
+radiation	O
+dose	O
+to	O
+predict	O
+the	O
+recurrence	O
+of	O
+prostate	O
+cancer	O
+following	O
+external	O
+beam	O
+radiation	O
+therapy	O
+(	O
+XRT	O
+)	O
+since	O
+the	O
+introduction	O
+of	O
+PSA	B-GENE
+as	O
+a	O
+tumor	O
+marker	O
+at	O
+one	O
+tertiary	O
+care	O
+center	O
+.	O
+
+To	O
+evaluate	O
+whether	O
+the	O
+human	O
+gene	O
+is	O
+also	O
+a	O
+target	O
+of	O
+thyroid	O
+hormone	O
+we	O
+have	O
+searched	O
+for	O
+T3	O
+-	O
+responsive	O
+elements	O
+in	O
+NRGN	B-GENE
+cloned	O
+genomic	O
+fragments	O
+spanning	O
+the	O
+whole	O
+gene	O
+.	O
+
+The	O
+transcriptional	O
+activity	O
+of	O
+PPARgamma	B-GENE
+is	O
+positively	O
+modulated	O
+by	O
+ligand	O
+binding	O
+and	O
+negatively	O
+regulated	O
+by	O
+phosphorylation	O
+mediated	O
+by	O
+the	O
+MEK	B-GENE
+/	O
+ERK	B-GENE
+signaling	O
+pathway	O
+.	O
+
+BACKGROUND	O
+:	O
+Diazepam	O
+,	O
+one	O
+of	O
+the	O
+benzodiazepine	O
+group	O
+of	O
+tranquilizers	O
+,	O
+is	O
+used	O
+as	O
+an	O
+adjunctive	O
+drug	O
+for	O
+sedation	O
+and	O
+for	O
+relief	O
+of	O
+anxiety	O
+in	O
+the	O
+treatment	O
+of	O
+epilepsy	O
+.	O
+
+Bioplastique	O
+granuloma	O
+presents	O
+with	O
+irregularly	O
+shaped	O
+cystic	O
+spaces	O
+of	O
+varying	O
+size	O
+containing	O
+jagged	O
+,	O
+translucent	O
+,	O
+nonbirefringent	O
+foreign	O
+bodies	O
+whereas	O
+Artecoll	O
+granuloma	O
+shows	O
+numerous	O
+round	O
+vacuoles	O
+nearly	O
+identical	O
+in	O
+size	O
+and	O
+shape	O
+enclosing	O
+round	O
+and	O
+sharply	O
+circumscribed	O
+,	O
+translucent	O
+,	O
+nonbirefringent	O
+foreign	O
+bodies	O
+.	O
+
+This	O
+Tbx6	B-GENE
+-	I-GENE
+subfamily	I-GENE
+gene	I-GENE
+is	O
+likely	O
+to	O
+participate	O
+in	O
+paraxial	O
+mesoderm	O
+formation	O
+and	O
+somitogenesis	O
+in	O
+human	O
+embryo	O
+.	O
+
+Structure	O
+-	O
+function	O
+analysis	O
+of	O
+the	O
+Z	O
+-	O
+DNA	O
+-	O
+binding	O
+domain	O
+Zalpha	O
+of	O
+dsRNA	B-GENE
+adenosine	I-GENE
+deaminase	I-GENE
+type	I-GENE
+I	I-GENE
+reveals	O
+similarity	O
+to	O
+the	O
+(	B-GENE
+alpha	I-GENE
++	I-GENE
+beta	I-GENE
+)	I-GENE
+family	I-GENE
+of	O
+helix	B-GENE
+-	I-GENE
+turn	I-GENE
+-	I-GENE
+helix	I-GENE
+proteins	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+regulation	O
+of	O
+Glvr	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+expression	O
+also	O
+has	O
+potential	O
+applications	O
+to	O
+gene	O
+therapy	O
+,	O
+since	O
+retroviral	O
+vectors	O
+carrying	O
+gibbon	B-GENE
+ape	I-GENE
+leukemia	I-GENE
+virus	I-GENE
+envelope	I-GENE
+proteins	I-GENE
+are	O
+used	O
+for	O
+gene	O
+delivery	O
+into	O
+different	O
+cell	O
+types	O
+.	O
+
+Carbohydrates	O
+and	O
+glycoconjugates	O
+biophysical	O
+methods	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+mouse	B-GENE
+glycolate	I-GENE
+oxidase	I-GENE
+.	O
+
+In	O
+such	O
+a	O
+manner	O
+,	O
+activated	O
+PKR	B-GENE
+inhibits	O
+cell	O
+growth	O
+and	O
+induces	O
+apoptosis	O
+,	O
+whereas	O
+disruption	O
+of	O
+normal	O
+PKR	B-GENE
+signaling	O
+results	O
+in	O
+unregulated	O
+cell	O
+growth	O
+.	O
+
+We	O
+isolated	O
+a	O
+ribosomal	B-GENE
+protein	I-GENE
+L18	I-GENE
+by	O
+interaction	O
+with	O
+PKR	B-GENE
+.	O
+
+Processing	O
+of	O
+the	O
+polycistronic	O
+precursor	O
+requires	O
+nucleases	O
+also	O
+involved	O
+in	O
+rRNA	O
+processing	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+Rnt1p	B-GENE
+and	O
+Rat1p	B-GENE
+.	O
+
+Furthermore	O
+,	O
+rhoA	B-GENE
+-	O
+mediated	O
+SRE	O
+activation	O
+was	O
+blocked	O
+by	O
+dominant	O
+negative	O
+mutants	O
+of	O
+PKC	B-GENE
+-	I-GENE
+alpha	I-GENE
+or	O
+PKC	B-GENE
+-	I-GENE
+epsilon	I-GENE
+.	O
+
+Nip7p	B-GENE
+-	O
+depleted	O
+cells	O
+exhibited	O
+the	O
+same	O
+defects	O
+as	O
+Nop8p	B-GENE
+-	O
+depleted	O
+cells	O
+,	O
+except	O
+that	O
+they	O
+accumulated	O
+27S	B-GENE
+precursors	I-GENE
+.	O
+
+We	O
+show	O
+that	O
+the	O
+Sm	B-GENE
+-	I-GENE
+binding	I-GENE
+site	I-GENE
+and	O
+stem	O
+-	O
+loop	O
+III	O
+structures	O
+are	O
+necessary	O
+for	O
+correct	O
+3	O
+'	O
+-	O
+end	O
+formation	O
+.	O
+
+Five	O
+different	O
+subtypes	O
+of	O
+spondyloarthropathy	O
+(	O
+SpA	O
+)	O
+are	O
+now	O
+recognized	O
+.	O
+
+Further	O
+experiments	O
+will	O
+be	O
+required	O
+to	O
+highlight	O
+the	O
+in	O
+vivo	O
+role	O
+of	O
+ELE1	B-GENE
+in	O
+nuclear	O
+receptor	O
+functioning	O
+.	O
+
+Overexpression	O
+of	O
+PTTG	B-GENE
+in	O
+transfected	O
+NIH	O
+3T3	O
+cells	O
+also	O
+stimulated	O
+expression	O
+and	O
+secretion	O
+of	O
+basic	B-GENE
+fibroblast	I-GENE
+growth	I-GENE
+factor	I-GENE
+,	O
+a	O
+human	B-GENE
+pituitary	I-GENE
+tumor	I-GENE
+growth	I-GENE
+-	I-GENE
+regulating	I-GENE
+factor	I-GENE
+.	O
+
+The	O
+perifascicular	O
+connective	O
+tissue	O
+sheath	O
+is	O
+important	O
+in	O
+organising	O
+the	O
+contraction	O
+of	O
+the	O
+myocardium	O
+by	O
+preventing	O
+lateral	O
+spread	O
+of	O
+conduction	O
+and	O
+by	O
+permitting	O
+transmission	O
+of	O
+the	O
+impulse	O
+only	O
+at	O
+the	O
+termination	O
+of	O
+the	O
+purkinje	O
+fibre	O
+.	O
+
+E1	B-GENE
+,	O
+a	O
+DNA	B-GENE
+helicase	I-GENE
+,	O
+collaborates	O
+with	O
+the	O
+HPV	B-GENE
+E2	I-GENE
+protein	I-GENE
+in	O
+ori	O
+-	O
+dependent	O
+replication	O
+.	O
+
+Here	O
+we	O
+describe	O
+a	O
+mutant	O
+alpha	O
+subunit	O
+designed	O
+to	O
+inhibit	O
+receptor	O
+-	O
+mediated	O
+hormonal	O
+activation	O
+of	O
+Gs	B-GENE
+,	O
+the	O
+stimulatory	O
+regulator	O
+of	O
+adenylyl	B-GENE
+cyclase	I-GENE
+.	O
+
+A	O
+gapped	O
+search	O
+with	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+CDED	B-GENE
+/	O
+LIOR	B-GENE
+revealed	O
+a	O
+36	O
+-	O
+41	O
+%	O
+similarity	O
+to	O
+several	O
+proteins	O
+related	O
+to	O
+signal	O
+transduction	O
+and	O
+cell	O
+replication	O
+,	O
+such	O
+as	O
+ORC1	B-GENE
+and	O
+KSR	B-GENE
+.	O
+
+Northern	O
+blot	O
+analysis	O
+demonstrated	O
+the	O
+ubiquitous	O
+expression	O
+of	O
+2	O
+.	O
+9	O
+kb	O
+and	O
+3	O
+.	O
+
+Additionally	O
+,	O
+a	O
+variety	O
+of	O
+regulatory	O
+schemes	O
+contribute	O
+temporal	O
+and	O
+/	O
+or	O
+spatial	O
+restriction	O
+to	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+responses	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+clinical	O
+profile	O
+of	O
+cavernous	O
+malformations	O
+with	O
+and	O
+without	O
+associated	O
+venous	O
+malformations	O
+.	O
+
+Magnetically	O
+induced	O
+optical	O
+self	O
+-	O
+pulsing	O
+in	O
+a	O
+nonlinear	O
+resonator	O
+.	O
+
+Wave	O
+cybernetics	O
+:	O
+A	O
+simple	O
+model	O
+of	O
+wave	O
+-	O
+controlled	O
+nonlinear	O
+and	O
+nonlocal	O
+cooperative	O
+phenomena	O
+.	O
+
+Autoionization	O
+rates	O
+and	O
+energy	O
+levels	O
+of	O
+triplet	O
+nf	O
+,	O
+v	O
+=	O
+1	O
+Rydberg	O
+states	O
+of	O
+H2	O
+.	O
+
+Unitary	O
+-	O
+group	O
+approach	O
+to	O
+spin	O
+-	O
+dependent	O
+operators	O
+.	O
+
+Nonlocal	O
+approach	O
+to	O
+scattering	O
+in	O
+a	O
+one	O
+-	O
+dimensional	O
+problem	O
+.	O
+
+Soft	O
+-	O
+x	O
+-	O
+ray	O
+lasing	O
+at	O
+32	O
+.	O
+6	O
+nm	O
+in	O
+Ne	O
+-	O
+like	O
+Ti	O
+ions	O
+driven	O
+by	O
+40	O
+J	O
+of	O
+energy	O
+from	O
+two	O
+650	O
+-	O
+ps	O
+laser	O
+pulses	O
+.	O
+
+Next	O
+,	O
+to	O
+identify	O
+regions	O
+of	O
+the	O
+promoter	O
+involved	O
+,	O
+we	O
+examined	O
+a	O
+series	O
+of	O
+tenascin	B-GENE
+-	I-GENE
+C	I-GENE
+promoter	I-GENE
+constructs	I-GENE
+with	O
+5	O
+'	O
+deletions	O
+and	O
+showed	O
+that	O
+denatured	O
+collagen	B-GENE
+-	I-GENE
+dependent	I-GENE
+promoter	I-GENE
+activity	O
+was	O
+retained	O
+by	O
+a	O
+122	O
+-	O
+base	O
+pair	O
+element	O
+,	O
+located	O
+-	O
+43	O
+to	O
+-	O
+165	O
+bp	O
+upstream	O
+of	O
+the	O
+RNA	O
+start	O
+site	O
+.	O
+
+Nuclear	B-GENE
+factor	I-GENE
+kappa	I-GENE
+B	I-GENE
+(	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+)	O
+is	O
+an	O
+important	O
+transcription	O
+factor	O
+for	O
+the	O
+genes	O
+of	O
+many	O
+pro	O
+-	O
+inflammatory	O
+proteins	O
+and	O
+is	O
+strongly	O
+activated	O
+by	O
+the	O
+cytokines	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+(	I-GENE
+TNF	I-GENE
+)	I-GENE
+alpha	I-GENE
+under	O
+various	O
+pathological	O
+conditions	O
+.	O
+
+Unilateral	O
+naris	O
+occlusion	O
+and	O
+the	O
+rat	O
+accessory	O
+olfactory	O
+bulb	O
+.	O
+
+The	O
+promoter	O
+of	O
+the	O
+rat	O
+pgp2	B-GENE
+/	O
+mdr1b	B-GENE
+gene	O
+has	O
+a	O
+GC	O
+-	O
+rich	O
+region	O
+(	O
+pgp2GC	B-GENE
+)	O
+that	O
+is	O
+highly	O
+conserved	O
+in	O
+mdr	B-GENE
+genes	I-GENE
+and	O
+contains	O
+an	O
+consensus	O
+Sp1	B-GENE
+site	I-GENE
+.	O
+
+Sp1	B-GENE
+'	O
+s	O
+role	O
+in	O
+transactivation	O
+of	O
+the	O
+pgp2	B-GENE
+/	O
+mdr1b	B-GENE
+promoter	O
+was	O
+tested	O
+in	O
+Drosophila	O
+Schneider	O
+cells	O
+.	O
+
+Measurements	O
+included	O
+bone	O
+mineral	O
+density	O
+of	O
+the	O
+lumbar	O
+spine	O
+and	O
+proximal	O
+femur	O
+(	O
+by	O
+dual	O
+-	O
+energy	O
+X	O
+-	O
+ray	O
+absorptiometry	O
+)	O
+and	O
+biochemical	O
+markers	O
+of	O
+bone	O
+remodeling	O
+(	O
+serum	O
+bone	O
+-	O
+specific	O
+alkaline	B-GENE
+phosphatase	I-GENE
+by	O
+immunoassay	O
+and	O
+urine	O
+deoxypyridinoline	O
+by	O
+high	O
+-	O
+pressure	O
+liquid	O
+chromatography	O
+)	O
+.	O
+
+Human	B-GENE
+MGP	I-GENE
+is	O
+a	O
+10	B-GENE
+-	I-GENE
+kD	I-GENE
+skeletal	I-GENE
+extracellular	I-GENE
+matrix	I-GENE
+(	I-GENE
+ECM	I-GENE
+)	I-GENE
+protein	I-GENE
+that	O
+consists	O
+of	O
+an	O
+84	O
+-	O
+aa	O
+mature	O
+protein	O
+and	O
+a	O
+19	O
+-	O
+aa	O
+transmembrane	O
+signal	O
+peptide	O
+.	O
+
+Dual	O
+roles	O
+of	O
+p82	B-GENE
+,	O
+the	O
+clam	O
+CPEB	B-GENE
+homolog	I-GENE
+,	O
+in	O
+cytoplasmic	O
+polyadenylation	O
+and	O
+translational	O
+masking	O
+.	O
+
+The	O
+pattern	O
+of	O
+RNase	B-GENE
+E	I-GENE
+digestion	O
+of	O
+finP305	B-GENE
+RNA	I-GENE
+differed	O
+from	O
+FinP	B-GENE
+,	O
+and	O
+GST	B-GENE
+-	O
+FinO	B-GENE
+did	O
+not	O
+protect	O
+finP305	B-GENE
+RNA	I-GENE
+from	O
+cleavage	O
+in	O
+vitro	O
+.	O
+
+Transcription	O
+readthrough	O
+into	O
+the	O
+inverted	O
+repeats	O
+has	O
+little	O
+effect	O
+on	O
+this	O
+event	O
+.	O
+
+In	O
+the	O
+second	O
+case	O
+,	O
+an	O
+epidermal	O
+cyst	O
+was	O
+diagnosed	O
+.	O
+
+MotA	B-GENE
+also	O
+binds	O
+a	O
+DNA	O
+sequence	O
+(	O
+a	O
+MotA	B-GENE
+box	I-GENE
+)	O
+,	O
+centered	O
+at	O
+position	O
+-	O
+30	O
+.	O
+
+We	O
+suggest	O
+that	O
+MotA	B-GENE
+and	O
+AsiA	B-GENE
+may	O
+function	O
+like	O
+certain	O
+eukaryotic	B-GENE
+TAFs	I-GENE
+(	O
+TATA	B-GENE
+binding	I-GENE
+protein	I-GENE
+(	I-GENE
+TBP	I-GENE
+)	I-GENE
+associated	I-GENE
+factors	I-GENE
+)	O
+whose	O
+binding	O
+to	O
+TBP	B-GENE
+results	O
+in	O
+transcription	O
+from	O
+new	O
+core	O
+promoter	O
+sequences	O
+.	O
+
+The	O
+S229A	O
+variant	O
+can	O
+better	O
+flip	O
+modified	O
+bases	O
+but	O
+does	O
+not	O
+tightly	O
+lock	O
+the	O
+flipped	O
+base	O
+into	O
+the	O
+adenine	O
+-	O
+binding	O
+pocket	O
+,	O
+suggesting	O
+that	O
+Ser229	O
+could	O
+form	O
+a	O
+contact	O
+to	O
+the	O
+flipped	O
+adenine	O
+.	O
+
+The	O
+high	O
+conservation	O
+of	O
+the	O
+3	O
+'	O
+terminus	O
+suggests	O
+that	O
+this	O
+region	O
+directs	O
+the	O
+assembly	O
+of	O
+proteins	O
+required	O
+for	O
+the	O
+initiation	O
+of	O
+RNA	O
+replication	O
+.	O
+
+All	O
+stimulations	O
+were	O
+down	O
+-	O
+regulated	O
+with	O
+GnRH	B-GENE
+-	I-GENE
+a	I-GENE
+commenced	O
+on	O
+day	O
+21	O
+in	O
+a	O
+long	O
+protocol	O
+before	O
+gonadotropin	B-GENE
+stimulation	O
+.	O
+
+The	O
+sequence	O
+up	O
+to	O
+-	O
+267	O
+bp	O
+relative	O
+to	O
+the	O
+transcription	O
+start	O
+site	O
+was	O
+sufficient	O
+to	O
+enhance	O
+reporter	O
+gene	O
+expression	O
+depending	O
+on	O
+the	O
+mesodermal	O
+differentiation	O
+of	O
+P19	O
+cells	O
+.	O
+
+No	O
+significant	O
+differences	O
+between	O
+the	O
+substituted	O
+and	O
+wild	O
+type	O
+peptides	O
+were	O
+observed	O
+,	O
+suggesting	O
+that	O
+this	O
+substitution	O
+in	O
+the	O
+intact	O
+protein	O
+may	O
+cause	O
+disruption	O
+of	O
+global	O
+rather	O
+than	O
+local	O
+structures	O
+.	O
+
+C3	B-GENE
+toxin	I-GENE
+completely	O
+inhibited	O
+RhoA	B-GENE
+function	O
+,	O
+partially	O
+inhibited	O
+SRE	O
+:	O
+Luc	B-GENE
+activity	O
+,	O
+but	O
+had	O
+no	O
+effect	O
+on	O
+LPA	O
+-	O
+stimulated	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+expression	O
+.	O
+
+However	O
+,	O
+C3	B-GENE
+toxin	I-GENE
+alone	O
+or	O
+in	O
+combination	O
+with	O
+growth	O
+factors	O
+did	O
+not	O
+stimulate	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+:	O
+Luc	B-GENE
+activity	O
+and	O
+actually	O
+antagonized	O
+the	O
+synergistic	O
+activation	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+:	O
+Luc	B-GENE
+observed	O
+in	O
+response	O
+to	O
+co	O
+-	O
+stimulation	O
+with	O
+growth	O
+factors	O
+and	O
+Ro	O
+-	O
+31	O
+-	O
+8220	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+examine	O
+the	O
+antimicrobial	O
+susceptibility	O
+to	O
+10	O
+currently	O
+used	O
+antimicrobial	O
+agents	O
+of	O
+50	O
+strains	O
+of	O
+P	O
+.	O
+acnes	O
+isolated	O
+from	O
+acne	O
+lesions	O
+and	O
+identified	O
+using	O
+a	O
+Rap	O
+ID	O
+ANA	O
+II	O
+panel	O
+.	O
+
+The	O
+role	O
+of	O
+intraoperative	O
+echocardiography	O
+in	O
+surgery	O
+of	O
+the	O
+heart	O
+and	O
+large	O
+vessels	O
+
+Taken	O
+together	O
+,	O
+our	O
+results	O
+demonstrate	O
+that	O
+CAP1	B-GENE
+is	O
+involved	O
+in	O
+multidrug	O
+resistance	O
+and	O
+oxidative	O
+stress	O
+response	O
+in	O
+C	O
+.	O
+albicans	O
+.	O
+
+Trinipatch	O
+is	O
+a	O
+small	O
+,	O
+transparent	O
+,	O
+matricial	O
+,	O
+monolayer	O
+patch	O
+with	O
+an	O
+absorption	O
+promoter	O
+,	O
+marketed	O
+in	O
+two	O
+dose	O
+-	O
+strengths	O
+(	O
+5	O
+mg	O
+/	O
+24	O
+h	O
+and	O
+10	O
+mg	O
+/	O
+24	O
+h	O
+)	O
+by	O
+Laboratoires	O
+Synthelabo	O
+.	O
+
+The	O
+RMRI	O
+was	O
+tested	O
+for	O
+interrater	O
+reliability	O
+using	O
+three	O
+simulated	O
+and	O
+10	O
+actual	O
+patients	O
+.	O
+
+The	O
+starting	O
+point	O
+is	O
+the	O
+consideration	O
+that	O
+the	O
+conceptions	O
+underlying	O
+the	O
+ICIDH	O
+are	O
+not	O
+suitable	O
+to	O
+serve	O
+as	O
+a	O
+mainstay	O
+of	O
+a	O
+model	O
+for	O
+diagnostics	O
+in	O
+rehabilitation	O
+because	O
+they	O
+do	O
+not	O
+reflect	O
+essential	O
+characteristics	O
+of	O
+the	O
+diagnostic	O
+process	O
+which	O
+is	O
+the	O
+basis	O
+for	O
+intervention	O
+.	O
+
+OBJECTIVE	O
+:	O
+This	O
+meta	O
+-	O
+analysis	O
+of	O
+67	O
+controlled	O
+trials	O
+was	O
+performed	O
+to	O
+quantify	O
+the	O
+cholesterol	O
+-	O
+lowering	O
+effect	O
+of	O
+major	O
+dietary	O
+fibers	O
+.	O
+
+When	O
+the	O
+high	O
+affinity	O
+hnRNP	B-GENE
+A1	I-GENE
+binding	I-GENE
+site	I-GENE
+was	O
+inserted	O
+into	O
+the	O
+beta	B-GENE
+-	I-GENE
+globin	I-GENE
+reporter	I-GENE
+,	O
+Rev	B-GENE
+was	O
+able	O
+to	O
+increase	O
+the	O
+cytoplasmic	O
+levels	O
+of	O
+unspliced	O
+mRNAs	O
+to	O
+14	O
+%	O
+.	O
+
+To	O
+date	O
+,	O
+two	O
+such	O
+proteins	O
+,	O
+PLZF	B-GENE
+and	O
+LAZ	B-GENE
+-	I-GENE
+3	I-GENE
+/	O
+BCL	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+have	O
+been	O
+implicated	O
+in	O
+oncogenesis	O
+.	O
+
+Overexpression	O
+of	O
+POG1	B-GENE
+inhibits	O
+alpha	B-GENE
+-	I-GENE
+factor	I-GENE
+-	O
+induced	O
+G1	O
+arrest	O
+and	O
+transcriptional	O
+repression	O
+of	O
+the	O
+CLN1	B-GENE
+and	O
+CLN2	B-GENE
+genes	I-GENE
+.	O
+
+We	O
+now	O
+show	O
+that	O
+RNU2	B-GENE
+fragility	O
+can	O
+be	O
+induced	O
+by	O
+transfection	O
+with	O
+an	O
+expression	O
+vector	O
+encoding	O
+Ad12	B-GENE
+E1B	I-GENE
+55	O
+kDa	O
+alone	O
+but	O
+not	O
+by	O
+an	O
+E1	B-GENE
+vector	O
+encoding	O
+all	O
+E1	B-GENE
+products	I-GENE
+(	O
+3	O
+E1A	B-GENE
+proteins	I-GENE
+,	O
+as	O
+well	O
+as	O
+the	O
+E1B	B-GENE
+19	O
+kDa	O
+and	O
+55	O
+kDa	O
+proteins	O
+)	O
+.	O
+
+Competitionsupershift	O
+EMSA	O
+assays	O
+revealed	O
+that	O
+multiple	O
+proteins	O
+were	O
+involved	O
+in	O
+bandshift	O
+complex	O
+formation	O
+with	O
+KCS	B-GENE
+,	O
+one	O
+of	O
+which	O
+was	O
+identified	O
+as	O
+factor	O
+Sp1	O
+.	O
+
+Similarity	O
+of	O
+DNA	O
+binding	O
+and	O
+transcriptional	O
+regulation	O
+by	O
+Caenorhabditis	B-GENE
+elegans	I-GENE
+MAB	I-GENE
+-	I-GENE
+3	I-GENE
+and	O
+Drosophila	B-GENE
+melanogaster	I-GENE
+DSX	I-GENE
+suggests	O
+conservation	O
+of	O
+sex	O
+determining	O
+mechanisms	O
+.	O
+
+Neither	O
+the	O
+p42	B-GENE
+/	I-GENE
+44	I-GENE
+nor	O
+the	O
+JNK	B-GENE
+pathway	O
+was	O
+involved	O
+in	O
+the	O
+action	O
+of	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+.	O
+
+In	O
+protocol	O
+2	O
+,	O
+eight	O
+different	O
+subjects	O
+performed	O
+Con	O
+and	O
+Ecc	O
+arm	O
+curls	O
+to	O
+fatigue	O
+,	O
+followed	O
+by	O
+postexercise	O
+muscle	O
+ischemia	O
+,	O
+by	O
+using	O
+the	O
+same	O
+resistance	O
+as	O
+in	O
+protocol	O
+1	O
+.	O
+
+Airflow	O
+was	O
+measured	O
+with	O
+a	O
+custom	O
+-	O
+designed	O
+turbine	O
+and	O
+a	O
+45	O
+-	O
+ft	O
+.	O
+-	O
+long	O
+cable	O
+to	O
+reach	O
+the	O
+volume	O
+-	O
+measuring	O
+module	O
+.	O
+
+Both	O
+mutations	O
+confer	O
+amino	O
+acid	O
+substitutions	O
+in	O
+the	O
+viral	B-GENE
+coat	I-GENE
+protein	I-GENE
+but	O
+differ	O
+in	O
+their	O
+relative	O
+abilities	O
+to	O
+utilize	O
+the	O
+foreign	O
+scaffolding	B-GENE
+protein	I-GENE
+.	O
+
+Complete	O
+recovery	O
+of	O
+liver	O
+function	O
+after	O
+this	O
+surgery	O
+tended	O
+to	O
+be	O
+slow	O
+.	O
+
+Although	O
+both	O
+transcripts	O
+share	O
+the	O
+first	O
+nine	O
+exons	O
+,	O
+exon	O
+10	O
+of	O
+ZIS	B-GENE
+-	I-GENE
+2	I-GENE
+is	O
+lacking	O
+in	O
+ZIS	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+instead	O
+,	O
+exon	O
+11	O
+(	O
+10th	O
+exon	O
+)	O
+of	O
+ZIS	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+larger	O
+in	O
+size	O
+,	O
+leading	O
+to	O
+the	O
+longer	O
+3	O
+'	O
+-	O
+UTR	O
+.	O
+
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+was	O
+elevated	O
+during	O
+active	O
+TB	O
+when	O
+compared	O
+with	O
+healthy	O
+controls	O
+,	O
+declining	O
+during	O
+and	O
+after	O
+treatment	O
+.	O
+
+The	O
+missing	O
+5	O
+'	O
+sequences	O
+were	O
+obtained	O
+by	O
+5	O
+'	O
+-	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+and	O
+by	O
+analysis	O
+of	O
+an	O
+NHE5	B-GENE
+genomic	I-GENE
+clone	I-GENE
+,	O
+and	O
+the	O
+missing	O
+3	O
+'	O
+sequences	O
+were	O
+obtained	O
+by	O
+3	O
+'	O
+-	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+.	O
+
+If	O
+no	O
+alloantibodies	O
+are	O
+detected	O
+,	O
+further	O
+analysis	O
+to	O
+define	O
+a	O
+role	O
+of	O
+drug	O
+-	O
+related	O
+or	O
+autoantibodies	O
+is	O
+required	O
+.	O
+
+This	O
+dependence	O
+,	O
+however	O
+,	O
+can	O
+be	O
+overcome	O
+to	O
+a	O
+large	O
+extent	O
+by	O
+dividing	O
+min	O
+LVdP	O
+/	O
+dt	O
+by	O
+mean	O
+aortic	O
+pressure	O
+.	O
+
+Genoa	O
+,	O
+Italy	O
+,	O
+24	O
+-	O
+28	O
+August	O
+1997	O
+.	O
+
+Electronic	O
+structure	O
+of	O
+delta	O
+-	O
+plutonium	O
+and	O
+of	O
+single	O
+Al	O
+,	O
+Ga	O
+,	O
+and	O
+Sc	O
+impurities	O
+in	O
+delta	O
+-	O
+plutonium	O
+.	O
+
+Bound	O
+-	O
+exciton	O
+transfer	O
+and	O
+photoluminescence	O
+undulation	O
+spectra	O
+for	O
+acceptors	O
+in	O
+ZnTe	O
+.	O
+
+Unified	O
+theory	O
+of	O
+segregated	O
+-	O
+stack	O
+organic	O
+charge	O
+-	O
+transfer	O
+solids	O
+:	O
+Magnetic	O
+properties	O
+.	O
+
+II	O
+.	O
+
+Envelope	O
+-	O
+function	O
+matching	O
+conditions	O
+for	O
+GaAs	O
+/	O
+(	O
+Al	O
+,	O
+Ga	O
+)	O
+As	O
+heterojunctions	O
+.	O
+
+Neutron	O
+scattering	O
+measurements	O
+of	O
+critical	O
+exponents	O
+in	O
+CsMnBr3	O
+:	O
+A	O
+Z2	O
+&	O
+gt	O
+;	O
+=	O
+1	O
+antiferromagnet	O
+.	O
+
+Thus	O
+,	O
+in	O
+normal	O
+intestinal	O
+epithelial	O
+goblet	O
+cells	O
+,	O
+TbetaRI	B-GENE
+and	O
+TbetaRII	B-GENE
+can	O
+respond	O
+to	O
+autocrine	O
+but	O
+not	O
+exogenous	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+without	O
+the	O
+participation	O
+of	O
+TbetaRIII	B-GENE
+.	O
+
+The	O
+history	O
+of	O
+exposure	O
+and	O
+carboxyhemoglobin	B-GENE
+levels	O
+should	O
+alert	O
+the	O
+physician	O
+to	O
+this	O
+diagnosis	O
+.	O
+
+The	O
+odds	O
+ratio	O
+for	O
+CHD	O
+was	O
+1	O
+.	O
+21	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+,	O
+0	O
+.	O
+84	O
+-	O
+1	O
+.	O
+75	O
+)	O
+given	O
+a	O
+positive	O
+serostatus	O
+of	O
+specific	O
+IgG	B-GENE
+antibodies	O
+after	O
+adjustment	O
+for	O
+covariates	O
+.	O
+
+Another	O
+group	O
+of	O
+HIPP	O
+-	O
+and	O
+HCX	O
+-	O
+lesioned	O
+animals	O
+trained	O
+on	O
+the	O
+tasks	O
+after	O
+the	O
+lesion	O
+showed	O
+reduced	O
+impairments	O
+of	O
+the	O
+type	O
+described	O
+above	O
+,	O
+suggesting	O
+that	O
+extrahippocampal	O
+structures	O
+trained	O
+after	O
+the	O
+lesion	O
+can	O
+assume	O
+the	O
+role	O
+of	O
+the	O
+hippocampus	O
+to	O
+some	O
+degree	O
+.	O
+
+The	O
+case	O
+for	O
+neutrinos	O
+from	O
+SN	O
+1987A	O
+.	O
+
+Scaling	O
+of	O
+fluctuations	O
+in	O
+one	O
+-	O
+dimensional	O
+interface	O
+and	O
+hopping	O
+models	O
+.	O
+
+Model	O
+of	O
+spatiotemporal	O
+dynamics	O
+of	O
+stick	O
+-	O
+slip	O
+motion	O
+.	O
+
+NMR	O
+of	O
+diffusing	O
+atoms	O
+in	O
+a	O
+periodic	O
+porous	O
+medium	O
+in	O
+the	O
+presence	O
+of	O
+a	O
+nonuniform	O
+magnetic	O
+field	O
+.	O
+
+Microstructure	O
+and	O
+conductivity	O
+of	O
+hierarchical	O
+laminate	O
+composites	O
+.	O
+
+Anisotropic	O
+heat	O
+transport	O
+in	O
+the	O
+octylcyanobiphenyl	O
+(	O
+8CB	O
+)	O
+liquid	O
+crystal	O
+.	O
+
+Direct	O
+approach	O
+to	O
+the	O
+study	O
+of	O
+soliton	O
+perturbations	O
+.	O
+
+Mutations	O
+affecting	O
+only	O
+CD4	B-GENE
+regulation	O
+mapped	O
+to	O
+residues	O
+previously	O
+shown	O
+to	O
+mediate	O
+the	O
+binding	O
+of	O
+Nef	B-GENE
+to	O
+this	O
+receptor	O
+,	O
+such	O
+as	O
+W57	O
+and	O
+L58	O
+,	O
+as	O
+well	O
+as	O
+to	O
+an	O
+AP	B-GENE
+-	I-GENE
+recruiting	I-GENE
+dileucine	I-GENE
+motif	I-GENE
+and	O
+to	O
+an	O
+acidic	O
+dipeptide	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+protein	O
+.	O
+
+The	O
+lytic	O
+cycle	O
+of	O
+KSHV	O
+,	O
+probably	O
+under	O
+the	O
+initial	O
+control	O
+of	O
+the	O
+KSHV	B-GENE
+/	I-GENE
+Rta	I-GENE
+gene	I-GENE
+,	O
+may	O
+directly	O
+contribute	O
+to	O
+tumor	O
+pathogenesis	O
+.	O
+
+We	O
+conclude	O
+that	O
+(	O
+i	O
+)	O
+we	O
+have	O
+identified	O
+several	O
+candidate	O
+latency	O
+genes	O
+of	O
+murine	O
+gammaHV68	O
+,	O
+(	O
+ii	O
+)	O
+expression	O
+of	O
+genes	O
+during	O
+latency	O
+may	O
+be	O
+different	O
+in	O
+different	O
+organs	O
+,	O
+consistent	O
+with	O
+multiple	O
+latency	O
+programs	O
+and	O
+/	O
+or	O
+multiple	O
+cellular	O
+sites	O
+of	O
+latency	O
+,	O
+and	O
+(	O
+iii	O
+)	O
+regions	O
+of	O
+the	O
+viral	O
+genome	O
+(	O
+v	B-GENE
+-	I-GENE
+bcl	I-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+,	O
+v	B-GENE
+-	I-GENE
+GCR	I-GENE
+gene	I-GENE
+,	O
+and	O
+gene	B-GENE
+73	I-GENE
+)	O
+are	O
+transcribed	O
+during	O
+latency	O
+with	O
+both	O
+gammaHV68	O
+and	O
+primate	O
+gammaherpesviruses	O
+.	O
+
+These	O
+data	O
+indicate	O
+a	O
+functional	O
+role	O
+for	O
+U1	B-GENE
+in	O
+NRS	B-GENE
+-	O
+mediated	O
+splicing	O
+inhibition	O
+.	O
+
+This	O
+suggests	O
+that	O
+the	O
+DcuS	B-GENE
+-	O
+DcuR	B-GENE
+system	O
+responds	O
+to	O
+external	O
+substrates	O
+.	O
+
+Crossover	O
+in	O
+the	O
+specific	O
+heat	O
+of	O
+dilute	O
+magnets	O
+induced	O
+by	O
+critical	O
+spin	O
+-	O
+wave	O
+dynamics	O
+.	O
+
+Erratum	O
+:	O
+Absence	O
+of	O
+precursor	O
+effects	O
+above	O
+the	O
+martensitic	O
+transformation	O
+in	O
+a	O
+virgin	O
+crystal	O
+of	O
+Li	O
+metal	O
+
+Interplane	O
+coupling	O
+in	O
+the	O
+superconductor	O
+Y2Ba4Cu7O15	O
+as	O
+revealed	O
+by	O
+NQR	O
+spin	O
+-	O
+echo	O
+double	O
+resonance	O
+.	O
+
+Electronic	O
+structure	O
+of	O
+a	O
+buried	O
+NiSi2	O
+or	O
+CoSi2	O
+layer	O
+in	O
+bulk	O
+Si	O
+.	O
+
+Raman	O
+investigation	O
+of	O
+YBa2	O
+-	O
+xLaxCu3O7	O
+ceramics	O
+.	O
+
+Effects	O
+of	O
+point	O
+defects	O
+on	O
+lattice	O
+parameters	O
+of	O
+semiconductors	O
+.	O
+
+Chaotic	O
+electron	O
+dynamics	O
+around	O
+a	O
+single	O
+elliptically	O
+shaped	O
+antidot	O
+.	O
+
+However	O
+,	O
+deletions	O
+of	O
+the	O
+C	O
+terminal	O
+11	O
+or	O
+14	O
+amino	O
+acids	O
+had	O
+more	O
+substantial	O
+effects	O
+.	O
+
+Sixty	O
+months	O
+after	O
+the	O
+initial	O
+vaccination	O
+,	O
+all	O
+vaccinees	O
+who	O
+received	O
+annual	O
+follow	O
+-	O
+up	O
+still	O
+had	O
+protective	O
+levels	O
+of	O
+anti	B-GENE
+-	I-GENE
+HAV	I-GENE
+.	O
+
+However	O
+,	O
+after	O
+PRK	O
+at	O
+5	O
+weeks	O
+of	O
+age	O
+,	O
+partial	O
+retreatment	O
+may	O
+be	O
+necessary	O
+due	O
+to	O
+regression	O
+of	O
+the	O
+PRK	O
+effect	O
+.	O
+
+Its	O
+early	O
+lesions	O
+were	O
+characterized	O
+by	O
+angiomatosis	O
+,	O
+vasculopathy	O
+,	O
+and	O
+proliferation	O
+of	O
+synoviocytes	O
+and	O
+fibroblasts	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+human	O
+cDNA	O
+encoding	O
+a	O
+novel	O
+beta1	B-GENE
+,	I-GENE
+6	I-GENE
+-	I-GENE
+N	I-GENE
+-	I-GENE
+acetylglucosaminyltransferase	I-GENE
+forming	O
+core	O
+2	O
+and	O
+core	O
+4	O
+.	O
+
+Interspecific	O
+mouse	O
+back	O
+-	O
+cross	O
+analysis	O
+identified	O
+the	O
+loci	O
+for	O
+mouse	B-GENE
+3Ost	I-GENE
+genes	I-GENE
+and	O
+syntenic	O
+assignments	O
+of	O
+corresponding	O
+human	O
+isologs	O
+were	O
+confirmed	O
+by	O
+the	O
+identification	O
+of	O
+mapped	O
+sequence	O
+-	O
+tagged	O
+site	O
+markers	O
+.	O
+
+The	O
+Scales	O
+of	O
+Cognitive	O
+Impairment	O
+Rated	O
+From	O
+Institutional	O
+Records	O
+(	O
+SCIRFIR	O
+)	O
+,	O
+a	O
+battery	O
+based	O
+on	O
+commonly	O
+used	O
+dementia	O
+rating	O
+instruments	O
+,	O
+was	O
+tested	O
+on	O
+the	O
+records	O
+of	O
+26	O
+chronically	O
+institutionalized	O
+,	O
+elderly	O
+schizophrenia	O
+patients	O
+,	O
+for	O
+the	O
+purpose	O
+of	O
+retrospectively	O
+evaluating	O
+the	O
+long	O
+-	O
+term	O
+course	O
+of	O
+cognitive	O
+change	O
+in	O
+schizophrenia	O
+and	O
+relating	O
+it	O
+to	O
+available	O
+autopsy	O
+materials	O
+.	O
+
+Most	O
+recently	O
+,	O
+the	O
+use	O
+of	O
+the	O
+product	O
+of	O
+brain	O
+weight	O
+and	O
+clearance	O
+has	O
+been	O
+proposed	O
+.	O
+
+Recombination	O
+and	O
+transcription	O
+of	O
+the	O
+endogenous	B-GENE
+Ig	I-GENE
+heavy	I-GENE
+chain	I-GENE
+locus	I-GENE
+is	O
+effected	O
+by	O
+the	O
+Ig	B-GENE
+heavy	I-GENE
+chain	I-GENE
+intronic	I-GENE
+enhancer	I-GENE
+core	I-GENE
+region	I-GENE
+in	O
+the	O
+absence	O
+of	O
+the	O
+matrix	O
+attachment	O
+regions	O
+.	O
+
+Two	O
+of	O
+these	O
+motifs	O
+are	O
+part	O
+of	O
+a	O
+highly	O
+conserved	O
+and	O
+inducible	O
+dyad	O
+symmetry	O
+element	O
+shown	O
+previously	O
+to	O
+control	O
+a	O
+remote	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+enhancer	I-GENE
+and	O
+the	O
+CD18	B-GENE
+promoter	I-GENE
+.	O
+
+In	O
+concert	O
+with	O
+the	O
+coactivator	O
+CREB	B-GENE
+binding	I-GENE
+protein	I-GENE
+/	O
+p300	B-GENE
+,	O
+which	O
+interacts	O
+with	O
+GABPalpha	B-GENE
+,	O
+the	O
+binding	O
+of	O
+GABPalpha	B-GENE
+and	I-GENE
+-	I-GENE
+beta	I-GENE
+to	O
+the	O
+dyad	O
+symmetry	O
+element	O
+controls	O
+the	O
+induction	O
+of	O
+IL	B-GENE
+-	I-GENE
+16	I-GENE
+promoter	I-GENE
+in	O
+T	O
+cells	O
+.	O
+
+TPO	B-GENE
+by	O
+itself	O
+did	O
+not	O
+activate	O
+ERK1	B-GENE
+,	O
+ERK2	B-GENE
+and	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+(	O
+PKC	B-GENE
+)	O
+,	O
+whereas	O
+TPO	B-GENE
+directly	O
+enhanced	O
+the	O
+PKC	B-GENE
+-	O
+dependent	O
+activation	O
+of	O
+ERKs	B-GENE
+induced	O
+by	O
+other	O
+agonists	O
+including	O
+thrombin	B-GENE
+and	O
+phorbol	O
+esters	O
+,	O
+without	O
+affecting	O
+the	O
+PKC	B-GENE
+activation	O
+by	O
+those	O
+agonists	O
+.	O
+
+BACKGROUND	O
+:	O
+In	O
+the	O
+ubiquitin	B-GENE
+-	O
+dependent	O
+proteolysis	O
+pathway	O
+,	O
+a	O
+ubiquitin	B-GENE
+ligase	I-GENE
+(	O
+E3	B-GENE
+)	O
+is	O
+responsible	O
+for	O
+substrate	O
+selectivity	O
+and	O
+timing	O
+of	O
+degradation	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Fission	B-GENE
+yeast	I-GENE
+SCF	I-GENE
+is	O
+composed	O
+of	O
+Pop1	B-GENE
+and	O
+Pop2	B-GENE
+,	O
+two	O
+structurally	O
+related	O
+but	O
+functionally	O
+independent	O
+F	B-GENE
+-	I-GENE
+box	I-GENE
+/	I-GENE
+WD	I-GENE
+-	I-GENE
+repeat	I-GENE
+proteins	I-GENE
+.	O
+
+19F	O
+NMR	O
+studies	O
+in	O
+ABF4	O
+-	O
+type	O
+layered	O
+antiferromagnets	O
+.	O
+
+Optical	O
+-	O
+absorption	O
+spectra	O
+,	O
+crystal	O
+-	O
+field	O
+energy	O
+levels	O
+,	O
+and	O
+transition	O
+line	O
+strengths	O
+of	O
+holmium	O
+in	O
+trigonal	O
+Na3	O
+
+Observation	O
+of	O
+dipolar	O
+interactions	O
+between	O
+Pb0	O
+defects	O
+at	O
+the	O
+(	O
+111	O
+)	O
+Si	O
+/	O
+SiO2	O
+interface	O
+.	O
+
+Quantum	O
+-	O
+statistical	O
+theory	O
+of	O
+high	O
+-	O
+field	O
+transport	O
+phenomena	O
+.	O
+
+NH3	O
+and	O
+NO	O
+interaction	O
+with	O
+Si	O
+(	O
+100	O
+)	O
+-	O
+(	O
+2	O
+x	O
+1	O
+)	O
+surfaces	O
+.	O
+
+Far	O
+-	O
+infrared	O
+hopping	O
+conductivity	O
+in	O
+the	O
+CuO	O
+chains	O
+of	O
+a	O
+single	O
+-	O
+domain	O
+YBa2Cu3O7	O
+-	O
+delta	O
+crystal	O
+.	O
+
+Surface	O
+spin	O
+waves	O
+in	O
+a	O
+Heisenberg	O
+ferrimagnet	O
+with	O
+a	O
+single	O
+-	O
+ion	O
+anisotropy	O
+(	O
+uniaxial	O
+and	O
+nonuniaxial	O
+)	O
+.	O
+
+Multilayer	O
+-	O
+relaxation	O
+geometry	O
+and	O
+electronic	O
+structure	O
+of	O
+a	O
+W	O
+(	O
+111	O
+)	O
+surface	O
+.	O
+
+Temperature	O
+dependence	O
+of	O
+the	O
+sublattice	O
+spontaneous	O
+magnetization	O
+of	O
+YBa2Cu3O6	O
+.	O
+
+GW	O
+Gamma	O
+approximation	O
+for	O
+electron	O
+self	O
+-	O
+energies	O
+in	O
+semiconductors	O
+and	O
+insulators	O
+.	O
+
+Precision	O
+measurement	O
+of	O
+the	O
+pion	O
+mass	O
+difference	O
+m	O
+pi	O
+-	O
+-	O
+m	O
+pi	O
+0	O
+.	O
+
+Testing	O
+gravity	O
+to	O
+second	O
+post	O
+-	O
+Newtonian	O
+order	O
+:	O
+A	O
+field	O
+-	O
+theory	O
+approach	O
+.	O
+
+Genetic	O
+experiments	O
+using	O
+mutants	O
+defective	O
+in	O
+apontic	B-GENE
+and	O
+bruno	B-GENE
+reveal	O
+a	O
+functional	O
+interaction	O
+between	O
+these	O
+genes	O
+.	O
+
+In	O
+the	O
+current	O
+model	O
+,	O
+Wingless	B-GENE
+/	O
+Wnt	B-GENE
+signal	O
+stabilizes	O
+Armadillo	B-GENE
+/	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+,	O
+which	O
+then	O
+accumulates	O
+in	O
+nuclei	O
+and	O
+binds	O
+TCF	B-GENE
+/	O
+LEF	B-GENE
+family	O
+proteins	O
+,	O
+forming	O
+bipartite	O
+transcription	O
+factors	O
+which	O
+activate	O
+transcription	O
+of	O
+Wingless	B-GENE
+/	O
+Wnt	B-GENE
+responsive	O
+genes	O
+.	O
+
+In	O
+support	O
+of	O
+clinical	O
+antianginal	O
+studies	O
+,	O
+the	O
+vasodilator	O
+nicorandil	O
+(	O
+NIC	O
+)	O
+was	O
+combined	O
+with	O
+the	O
+beta	B-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptor	I-GENE
+antagonists	O
+propranolol	O
+(	O
+PRO	O
+)	O
+and	O
+atenolol	O
+(	O
+ATN	O
+)	O
+and	O
+with	O
+the	O
+calcium	O
+channel	O
+blocker	O
+diltiazem	O
+(	O
+DTZ	O
+)	O
+to	O
+determine	O
+their	O
+cardiovascular	O
+and	O
+pharmacokinetic	O
+interactions	O
+.	O
+
+Elimination	O
+of	O
+ETH1	B-GENE
+in	O
+apn1	B-GENE
+strains	O
+also	O
+increased	O
+spontaneous	O
+mutation	O
+rates	O
+9	O
+-	O
+or	O
+31	O
+-	O
+fold	O
+compared	O
+to	O
+the	O
+wild	O
+type	O
+as	O
+determined	O
+by	O
+reversion	O
+to	O
+adenine	O
+or	O
+lysine	O
+prototrophy	O
+,	O
+respectively	O
+.	O
+
+Elimination	O
+of	O
+ETH1	B-GENE
+in	O
+apn1	B-GENE
+strains	O
+also	O
+increased	O
+spontaneous	O
+mutation	O
+rates	O
+9	O
+-	O
+or	O
+31	O
+-	O
+fold	O
+compared	O
+to	O
+the	O
+wild	O
+type	O
+as	O
+determined	O
+by	O
+reversion	O
+to	O
+adenine	O
+or	O
+lysine	O
+prototrophy	O
+,	O
+respectively	O
+.	O
+
+Mammalian	O
+Ras	B-GENE
+GTPase	B-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+(	O
+GAP	B-GENE
+)	O
+,	O
+p120	B-GENE
+Ras	B-GENE
+-	O
+GAP	B-GENE
+,	O
+has	O
+been	O
+implicated	O
+as	O
+both	O
+a	O
+downregulator	O
+and	O
+effector	O
+of	O
+Ras	B-GENE
+proteins	I-GENE
+,	O
+but	O
+its	O
+precise	O
+role	O
+in	O
+Ras	B-GENE
+-	O
+mediated	O
+signal	O
+transduction	O
+pathways	O
+is	O
+unclear	O
+.	O
+
+Three	O
+mog	B-GENE
+-	I-GENE
+1	I-GENE
+alleles	I-GENE
+possess	O
+premature	O
+stop	O
+codons	O
+and	O
+are	O
+likely	O
+to	O
+be	O
+null	O
+alleles	O
+,	O
+and	O
+one	O
+is	O
+a	O
+missense	O
+mutation	O
+and	O
+is	O
+likely	O
+to	O
+retain	O
+residual	O
+activity	O
+.	O
+mog	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+is	O
+expressed	O
+in	O
+both	O
+germ	O
+line	O
+and	O
+somatic	O
+tissues	O
+and	O
+appears	O
+to	O
+be	O
+ubiquitous	O
+.	O
+
+However	O
+,	O
+unlike	O
+the	O
+SIN3	B-GENE
+gene	I-GENE
+of	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+pst1	B-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+is	O
+essential	O
+for	O
+cell	O
+viability	O
+.	O
+
+The	O
+Nmd3	B-GENE
+protein	I-GENE
+sequence	I-GENE
+does	O
+not	O
+contain	O
+readily	O
+recognizable	O
+motifs	O
+of	O
+known	O
+function	O
+.	O
+
+The	O
+distribution	O
+of	O
+the	O
+various	O
+repeats	O
+suggests	O
+its	O
+organization	O
+is	O
+similar	O
+to	O
+the	O
+beta	O
+-	O
+heterochromatic	O
+regions	O
+near	O
+the	O
+base	O
+of	O
+the	O
+major	O
+chromosome	O
+arms	O
+.	O
+
+Calcitonin	B-GENE
+simultaneously	O
+regulates	O
+both	O
+periosteal	O
+hyperostosis	O
+and	O
+trabecular	O
+osteopenia	O
+in	O
+the	O
+spinal	O
+hyperostotic	O
+mouse	O
+(	O
+twy	B-GENE
+/	O
+twy	B-GENE
+)	O
+in	O
+vivo	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+also	O
+show	O
+that	O
+cdk7	B-GENE
+may	O
+phosphorylate	O
+the	O
+carboxy	O
+-	O
+terminal	O
+domain	O
+(	O
+CTD	O
+)	O
+of	O
+RNA	B-GENE
+pol	I-GENE
+II	I-GENE
+in	O
+the	O
+absence	O
+of	O
+promoter	O
+opening	O
+.	O
+
+The	O
+therapy	O
+with	O
+a	O
+H2	B-GENE
+-	I-GENE
+receptor	I-GENE
+antagonist	O
+is	O
+less	O
+effective	O
+than	O
+the	O
+triple	O
+therapies	O
+with	O
+omeprazole	O
+or	O
+lansoprazole	O
+.	O
+
+In	O
+humans	O
+,	O
+three	O
+tissue	B-GENE
+-	I-GENE
+specific	I-GENE
+plastin	I-GENE
+isoforms	I-GENE
+have	O
+been	O
+identified	O
+.	O
+
+No	O
+TATA	O
+or	O
+Inr	O
+sequence	O
+was	O
+found	O
+.	O
+
+The	O
+inhibition	O
+by	O
+the	O
+RIalpha	B-GENE
+subunit	I-GENE
+is	O
+reversed	O
+by	O
+addition	O
+of	O
+nanomolar	O
+concentrations	O
+of	O
+cAMP	O
+(	O
+Ka	O
+=	O
+40	O
+nM	O
+)	O
+,	O
+thus	O
+demonstrating	O
+that	O
+PrKX	B-GENE
+is	O
+a	O
+novel	O
+,	O
+type	B-GENE
+I	I-GENE
+cAMP	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+that	O
+is	O
+activated	O
+at	O
+lower	O
+cAMP	O
+concentrations	O
+than	O
+the	O
+holoenzyme	O
+with	O
+the	O
+Calpha	B-GENE
+subunit	I-GENE
+of	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+in	O
+vitro	O
+mutagenesis	O
+of	O
+both	O
+Engrailed	B-GENE
+and	O
+Pbx1	B-GENE
+sites	I-GENE
+indicated	O
+that	O
+other	O
+unidentified	O
+sites	O
+are	O
+responsible	O
+for	O
+the	O
+transcriptional	O
+enhancement	O
+observed	O
+with	O
+the	O
+intronic	O
+fragment	O
+.	O
+
+Several	O
+secondary	O
+structure	O
+elements	O
+were	O
+identified	O
+.	O
+
+Here	O
+,	O
+we	O
+evidence	O
+that	O
+the	O
+developmental	O
+functions	O
+of	O
+the	O
+family	O
+of	O
+transcription	O
+factors	O
+characterized	O
+by	O
+the	O
+POU	B-GENE
+DNA	I-GENE
+binding	I-GENE
+motif	I-GENE
+exerts	O
+roles	O
+in	O
+mammalian	O
+development	O
+.	O
+
+High	O
+-	O
+affinity	O
+site	O
+-	O
+specific	O
+DNA	O
+binding	O
+by	O
+POU	B-GENE
+domain	I-GENE
+transcription	I-GENE
+factors	I-GENE
+requires	O
+both	O
+the	O
+POU	B-GENE
+-	I-GENE
+specific	I-GENE
+and	O
+the	O
+POU	B-GENE
+-	I-GENE
+homeodomain	I-GENE
+.	O
+
+In	O
+the	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+crystal	O
+,	O
+the	O
+POU	B-GENE
+-	I-GENE
+specific	I-GENE
+domain	I-GENE
+recognizes	O
+a	O
+GCAT	O
+half	O
+-	O
+site	O
+,	O
+while	O
+the	O
+corresponding	O
+sequence	O
+recognized	O
+by	O
+the	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+POU	B-GENE
+-	O
+specific	O
+domain	O
+,	O
+GTAT	O
+,	O
+is	O
+on	O
+the	O
+opposing	O
+strand	O
+.	O
+
+Most	O
+other	O
+end	O
+points	O
+were	O
+highly	O
+significant	O
+,	O
+and	O
+death	O
+,	O
+which	O
+was	O
+monitored	O
+across	O
+the	O
+U	O
+.	O
+S	O
+.	O
+program	O
+,	O
+was	O
+different	O
+with	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+.	O
+
+The	O
+other	O
+is	O
+located	O
+at	O
+-	O
+1335	O
+,	O
+outside	O
+this	O
+highly	O
+conserved	O
+region	O
+.	O
+
+Those	O
+radiological	O
+aspects	O
+were	O
+distributed	O
+in	O
+two	O
+categories	O
+:	O
+1	O
+)	O
+type	O
+I	O
+-	O
+presenting	O
+variable	O
+sinusoidal	O
+filling	O
+.	O
+
+Results	O
+demonstrated	O
+that	O
+the	O
+presence	O
+of	O
+myofibroblasts	O
+varied	O
+considerably	O
+from	O
+case	O
+to	O
+case	O
+and	O
+was	O
+always	O
+related	O
+to	O
+smooth	O
+muscle	O
+cell	O
+dispersion	O
+,	O
+which	O
+occurred	O
+around	O
+medium	O
+-	O
+sized	O
+damaged	O
+portal	O
+vein	O
+branches	O
+.	O
+
+Radiative	O
+corrections	O
+to	O
+beta	O
+decay	O
+and	O
+the	O
+possibility	O
+of	O
+a	O
+fourth	O
+generation	O
+.	O
+
+Depth	O
+-	O
+controlled	O
+grazing	O
+-	O
+incidence	O
+diffraction	O
+of	O
+synchrotron	O
+x	O
+radiation	O
+.	O
+
+Oscillatory	O
+exchange	O
+of	O
+atoms	O
+between	O
+traps	O
+containing	O
+Bose	O
+condensates	O
+.	O
+
+Structure	O
+determination	O
+of	O
+an	O
+adsorbate	O
+-	O
+induced	O
+multilayer	O
+reconstruction	O
+:	O
+(	O
+1	O
+x	O
+2	O
+)	O
+-	O
+H	O
+/	O
+Ni	O
+(	O
+110	O
+)	O
+.	O
+
+Magnetic	O
+trapping	O
+of	O
+spin	O
+-	O
+polarized	O
+atomic	O
+hydrogen	O
+.	O
+
+Northern	O
+blot	O
+and	O
+in	O
+situ	O
+hybridization	O
+analyses	O
+revealed	O
+GPR34	B-GENE
+mRNA	I-GENE
+transcripts	I-GENE
+in	O
+several	O
+human	O
+and	O
+rat	O
+brain	O
+regions	O
+.	O
+
+The	O
+microphthalmia	B-GENE
+-	I-GENE
+TFE	I-GENE
+(	O
+MiT	B-GENE
+)	O
+subfamily	O
+of	O
+basic	B-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+(	I-GENE
+bHLH	I-GENE
+-	I-GENE
+ZIP	I-GENE
+)	I-GENE
+transcription	I-GENE
+factors	I-GENE
+,	O
+including	O
+TFE3	B-GENE
+,	O
+TFEB	B-GENE
+,	O
+TFEC	B-GENE
+,	O
+and	O
+Mitf	B-GENE
+,	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+regulation	O
+of	O
+tissue	O
+-	O
+specific	O
+gene	O
+expression	O
+in	O
+several	O
+cell	O
+lineages	O
+.	O
+
+Fifty	O
+-	O
+seven	O
+patients	O
+aged	O
+<	O
+55	O
+years	O
+with	O
+acute	O
+lymphoblastic	O
+leukemia	O
+(	O
+ALL	O
+)	O
+in	O
+second	O
+or	O
+third	O
+bone	O
+marrow	O
+(	O
+BM	O
+)	O
+relapse	O
+or	O
+refractory	O
+to	O
+first	O
+-	O
+line	O
+therapy	O
+were	O
+enrolled	O
+in	O
+an	O
+Italian	O
+cooperative	O
+study	O
+.	O
+
+The	O
+dorsal	O
+nerves	O
+of	O
+the	O
+penis	O
+were	O
+anesthetized	O
+bilaterally	O
+with	O
+lidocaine	O
+.	O
+
+Early	O
+-	O
+onset	O
+scleral	O
+necrosis	O
+after	O
+iodine	O
+I	O
+125	O
+plaque	O
+radiotherapy	O
+for	O
+ciliochoroidal	O
+melanoma	O
+.	O
+
+Successful	O
+interaction	O
+of	O
+ARF	B-GENE
+and	O
+PKC	B-GENE
+-	I-GENE
+alpha	I-GENE
+with	O
+PLD1	B-GENE
+was	O
+not	O
+achieved	O
+,	O
+but	O
+a	O
+C	O
+-	O
+terminal	O
+fragment	O
+of	O
+human	B-GENE
+PLD1	I-GENE
+(	O
+denoted	O
+"	O
+D4	O
+"	O
+)	O
+interacted	O
+with	O
+the	O
+active	O
+mutant	O
+of	O
+RhoA	B-GENE
+,	O
+RhoAVal	B-GENE
+-	I-GENE
+14	I-GENE
+.	O
+
+Vacuum	O
+Rabi	O
+splitting	O
+as	O
+a	O
+feature	O
+of	O
+linear	O
+-	O
+dispersion	O
+theory	O
+:	O
+Analysis	O
+and	O
+experimental	O
+observations	O
+.	O
+
+High	O
+-	O
+pressure	O
+effects	O
+on	O
+ultrafast	O
+-	O
+relaxation	O
+kinetics	O
+of	O
+excitons	O
+in	O
+polydiacetylene	O
+4BCMU	O
+.	O
+
+Drag	O
+reduction	O
+in	O
+turbulent	O
+flows	O
+by	O
+polymers	O
+.	O
+
+Large	O
+scale	O
+electronic	O
+structure	O
+calculations	O
+.	O
+
+Current	O
+world	O
+literature	O
+.	O
+
+These	O
+results	O
+show	O
+that	O
+Ski	B-GENE
+is	O
+a	O
+component	O
+of	O
+the	O
+HDAC	B-GENE
+complex	I-GENE
+and	O
+that	O
+Ski	B-GENE
+is	O
+required	O
+for	O
+the	O
+transcriptional	O
+repression	O
+mediated	O
+by	O
+this	O
+complex	O
+.	O
+
+Recombinant	O
+unr	B-GENE
+acts	O
+synergistically	O
+with	O
+recombinant	O
+PTB	B-GENE
+to	O
+stimulate	O
+translation	O
+dependent	O
+on	O
+the	O
+rhinovirus	O
+IRES	O
+.	O
+
+Analysis	O
+of	O
+the	O
+consensus	O
+binding	O
+sequence	O
+and	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+ZF5	B-GENE
+.	O
+
+Mapping	O
+of	O
+the	O
+human	B-GENE
+Voltage	I-GENE
+-	I-GENE
+Dependent	I-GENE
+Anion	I-GENE
+Channel	I-GENE
+isoforms	I-GENE
+1	I-GENE
+and	I-GENE
+2	I-GENE
+reconsidered	O
+.	O
+
+Identification	O
+of	O
+RNase	B-GENE
+T	I-GENE
+as	O
+a	O
+high	O
+-	O
+copy	O
+suppressor	O
+of	O
+the	O
+UV	O
+sensitivity	O
+associated	O
+with	O
+single	B-GENE
+-	I-GENE
+strand	I-GENE
+DNA	I-GENE
+exonuclease	I-GENE
+deficiency	O
+in	O
+Escherichia	O
+coli	O
+.	O
+
+Inhibition	O
+of	O
+phosphatidylinositol	B-GENE
+-	I-GENE
+3	I-GENE
+kinase	I-GENE
+did	O
+not	O
+have	O
+a	O
+significant	O
+effect	O
+on	O
+p53	B-GENE
+conformation	O
+but	O
+did	O
+have	O
+a	O
+weak	O
+but	O
+significant	O
+effect	O
+on	O
+Tpo	B-GENE
+-	O
+enhanced	O
+viability	O
+.	O
+
+No	O
+difference	O
+in	O
+percentage	O
+of	O
+males	O
+in	O
+semen	O
+production	O
+was	O
+noted	O
+between	O
+strains	O
+,	O
+CP	O
+levels	O
+,	O
+or	O
+feeding	O
+regimens	O
+.	O
+
+Further	O
+analysis	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+DNA	O
+binding	O
+activities	O
+in	O
+7	O
+-	O
+to	O
+14	O
+-	O
+day	O
+culture	O
+activated	O
+HSCs	O
+led	O
+to	O
+the	O
+discovery	O
+of	O
+high	B-GENE
+mobility	I-GENE
+AP	I-GENE
+-	I-GENE
+1	I-GENE
+complexes	I-GENE
+(	O
+HMAP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+Mutations	O
+of	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+of	O
+the	O
+TIMP	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+that	O
+prevented	O
+formation	O
+of	O
+HMAP	B-GENE
+-	I-GENE
+1	I-GENE
+caused	O
+a	O
+70	O
+%	O
+loss	O
+of	O
+activity	O
+in	O
+transfected	O
+activated	O
+HSCs	O
+.	O
+
+STUDY	O
+DESIGN	O
+:	O
+Salivary	B-GENE
+immunoglobulin	I-GENE
+A	I-GENE
+levels	O
+of	O
+each	O
+of	O
+20	O
+subjects	O
+were	O
+determined	O
+on	O
+3	O
+occasions	O
+:	O
+first	O
+,	O
+while	O
+the	O
+subject	O
+was	O
+still	O
+smoking	O
+;	O
+second	O
+,	O
+7	O
+days	O
+after	O
+cessation	O
+of	O
+smoking	O
+;	O
+third	O
+,	O
+on	O
+the	O
+14th	O
+day	O
+after	O
+cessation	O
+.	O
+
+Role	O
+of	O
+g2	O
+in	O
+relating	O
+the	O
+Schwinger	O
+and	O
+Gerasimov	O
+-	O
+Drell	O
+-	O
+Hearn	O
+sum	O
+rules	O
+.	O
+
+Spectroscopy	O
+of	O
+negative	O
+ions	O
+utilizing	O
+multiphoton	O
+detachment	O
+in	O
+a	O
+Raman	O
+coupling	O
+regime	O
+.	O
+
+Band	O
+structure	O
+effects	O
+of	O
+transport	O
+properties	O
+in	O
+icosahedral	O
+quasicrystals	O
+.	O
+
+Acoustic	O
+transmission	O
+spectra	O
+in	O
+the	O
+Penrose	O
+lattice	O
+.	O
+
+Two	O
+-	O
+Channel	O
+Kondo	O
+Lattice	O
+:	O
+An	O
+Incoherent	O
+Metal	O
+.	O
+
+Basal	O
+midexpiratory	O
+lower	O
+esophageal	O
+sphincter	O
+pressure	O
+was	O
+similar	O
+in	O
+the	O
+study	O
+group	O
+(	O
+mean	O
+[	O
+SD	O
+]	O
+20	O
+.	O
+1	O
+[	O
+9	O
+.	O
+1	O
+]	O
+mmHg	O
+)	O
+and	O
+controls	O
+(	O
+17	O
+.	O
+6	O
+[	O
+6	O
+.	O
+0	O
+]	O
+mmHg	O
+)	O
+;	O
+the	O
+pressure	O
+did	O
+not	O
+change	O
+following	O
+EVS	O
+or	O
+EVL	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+subjects	O
+with	O
+air	O
+trapping	O
+(	O
+residual	O
+volume	O
+(	O
+RV	O
+)	O
+/	O
+total	O
+lung	O
+capacity	O
+(	O
+TLC	O
+)	O
+>	O
+37	O
+%	O
+)	O
+disclosed	O
+not	O
+only	O
+a	O
+higher	O
+n	O
+(	O
+mit	O
+)	O
+(	O
+0	O
+.	O
+63	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+versus	O
+0	O
+.	O
+43	O
++	O
+/	O
+-	O
+0	O
+.	O
+07	O
+mt	O
+x	O
+microm	O
+(	O
+-	O
+2	O
+)	O
+,	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+but	O
+shorter	O
+sarcomeres	O
+(	O
+L	O
+(	O
+sar	O
+)	O
+)	O
+than	O
+subjects	O
+without	O
+this	O
+functional	O
+abnormality	O
+(	O
+2	O
+.	O
+08	O
++	O
+/	O
+-	O
+0	O
+.	O
+16	O
+to	O
+2	O
+.	O
+27	O
++	O
+/	O
+-	O
+0	O
+.	O
+15	O
+microm	O
+,	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Cyclin	B-GENE
+D1	I-GENE
+-	I-GENE
+associated	I-GENE
+kinase	I-GENE
+activity	O
+and	O
+protein	O
+levels	O
+were	O
+increased	O
+in	O
+mammary	O
+tumors	O
+from	O
+murine	O
+mammary	O
+tumor	O
+virus	O
+-	O
+pp60	B-GENE
+(	O
+c	B-GENE
+-	I-GENE
+src527F	I-GENE
+)	O
+transgenic	O
+mice	O
+.	O
+
+The	O
+SH2	B-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+inositol	I-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+phosphatase	I-GENE
+(	O
+SHIP	B-GENE
+)	O
+recruits	O
+the	O
+p85	B-GENE
+subunit	I-GENE
+of	O
+phosphoinositide	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+during	O
+FcgammaRIIb1	B-GENE
+-	O
+mediated	O
+inhibition	O
+of	O
+B	B-GENE
+cell	I-GENE
+receptor	I-GENE
+signaling	O
+.	O
+
+An	O
+increase	O
+in	O
+bone	O
+mineral	O
+density	O
+at	O
+the	O
+spine	O
+,	O
+total	O
+hip	O
+,	O
+and	O
+total	O
+body	O
+has	O
+been	O
+reported	O
+with	O
+raloxifene	O
+but	O
+seems	O
+to	O
+be	O
+less	O
+than	O
+that	O
+seen	O
+with	O
+estrogen	O
+or	O
+alendronate	O
+therapy	O
+.	O
+
+However	O
+,	O
+in	O
+those	O
+studies	O
+due	O
+to	O
+the	O
+presence	O
+of	O
+thiol	O
+agents	O
+in	O
+the	O
+PKC	B-GENE
+preparations	O
+,	O
+the	O
+sensitive	O
+reaction	O
+of	O
+BPO	O
+with	O
+redox	O
+-	O
+active	O
+cysteine	O
+residues	O
+in	O
+PKC	B-GENE
+was	O
+not	O
+observed	O
+.	O
+
+Interestingly	O
+,	O
+Csx	B-GENE
+/	O
+Nkx2	B-GENE
+.	O
+
+We	O
+also	O
+identified	O
+an	O
+alternative	O
+spliced	O
+form	O
+of	O
+Lyp	B-GENE
+RNA	I-GENE
+,	O
+Lyp2	B-GENE
+.	O
+
+The	O
+costs	O
+were	O
+DM	O
+11	O
+,	O
+562	O
+for	O
+a	O
+PE	O
+,	O
+DM	O
+12	O
+,	O
+477	O
+for	O
+a	O
+VR	O
+and	O
+DM	O
+7	O
+,	O
+532	O
+for	O
+a	O
+MR	O
+.	O
+
+We	O
+now	O
+provide	O
+evidence	O
+for	O
+physical	O
+and	O
+functional	O
+interaction	O
+between	O
+Doa4	B-GENE
+and	O
+the	O
+proteasome	O
+.	O
+
+Nipponbare	O
+as	O
+well	O
+as	O
+O	O
+.	O
+australiensis	O
+.	O
+
+In	O
+addition	O
+,	O
+mapping	O
+of	O
+the	O
+promoter	O
+region	O
+and	O
+the	O
+identification	O
+of	O
+putative	O
+promoter	O
+regulatory	O
+sequences	O
+should	O
+give	O
+insight	O
+into	O
+the	O
+transcriptional	O
+regulation	O
+of	O
+UCP2	B-GENE
+expression	O
+-	O
+-	O
+in	O
+particular	O
+by	O
+anyone	O
+of	O
+the	O
+above	O
+mentioned	O
+factors	O
+-	O
+-	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+The	O
+rate	O
+of	O
+resectability	O
+is	O
+low	O
+and	O
+5	O
+-	O
+year	O
+survival	O
+is	O
+very	O
+poor	O
+.	O
+
+In	O
+order	O
+to	O
+better	O
+characterize	O
+the	O
+distribution	O
+of	O
+ML	O
+and	O
+MAP	O
+estimates	O
+under	O
+these	O
+conditions	O
+,	O
+we	O
+derive	O
+a	O
+point	O
+approximation	O
+to	O
+density	O
+values	O
+of	O
+the	O
+conditional	O
+distribution	O
+of	O
+such	O
+estimates	O
+.	O
+
+RT	O
+-	O
+PCR	O
+was	O
+performed	O
+using	O
+previously	O
+reported	O
+degenerate	O
+oligonucleotide	O
+primers	O
+to	O
+the	O
+ligand	O
+binding	O
+domain	O
+(	O
+LBD	O
+)	O
+of	O
+known	O
+beta	B-GENE
+integrin	I-GENE
+subunits	I-GENE
+and	O
+Bge	B-GENE
+cDNA	I-GENE
+.	O
+
+The	O
+lowest	O
+culture	O
+failure	O
+rate	O
+of	O
+0	O
+.	O
+2	O
+per	O
+cent	O
+was	O
+found	O
+after	O
+EAF	O
+compared	O
+with	O
+0	O
+.	O
+9	O
+per	O
+cent	O
+among	O
+CVS	O
+.	O
+
+Ectopic	O
+expression	O
+of	O
+d	B-GENE
+-	I-GENE
+axin	I-GENE
+inhibited	O
+Wingless	B-GENE
+signaling	O
+.	O
+
+The	O
+corresponding	O
+differences	O
+in	O
+FVIIa	B-GENE
+and	O
+PAI	B-GENE
+-	I-GENE
+1	I-GENE
+were	O
+not	O
+statistically	O
+significant	O
+.	O
+
+On	O
+the	O
+other	O
+side	O
+,	O
+when	O
+the	O
+aortic	O
+ring	O
+was	O
+perfused	O
+with	O
+L	O
+-	O
+NNA	O
+(	O
+NO	O
+-	O
+synthesis	O
+inhibitor	O
+)	O
+or	O
+methylene	O
+blue	O
+(	O
+soluble	O
+cGMPase	B-GENE
+inhibitor	O
+)	O
+,	O
+the	O
+changes	O
+could	O
+be	O
+attenuated	O
+.	O
+
+Nevertheless	O
+,	O
+inactivation	O
+of	O
+the	O
+cyclin	B-GENE
+E	I-GENE
+-	O
+Cdk2	B-GENE
+complex	O
+in	O
+response	O
+to	O
+mitogen	O
+starvation	O
+occurs	O
+normally	O
+in	O
+MEFs	O
+that	O
+have	O
+a	O
+homozygous	O
+deletion	O
+of	O
+the	O
+p27	B-GENE
+gene	I-GENE
+.	O
+
+Identification	O
+and	O
+characterization	O
+of	O
+IS2404	B-GENE
+and	O
+IS2606	B-GENE
+:	O
+two	O
+distinct	O
+repeated	O
+sequences	O
+for	O
+detection	O
+of	O
+Mycobacterium	O
+ulcerans	O
+by	O
+PCR	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+results	O
+are	O
+consistent	O
+with	O
+the	O
+possibility	O
+that	O
+p202	B-GENE
+protein	I-GENE
+contributes	O
+to	O
+the	O
+cell	O
+growth	O
+retardation	O
+activity	O
+of	O
+the	O
+IFNs	B-GENE
+,	O
+at	O
+least	O
+in	O
+part	O
+,	O
+by	O
+modulating	O
+p21	B-GENE
+protein	I-GENE
+levels	O
+.	O
+
+Similar	O
+results	O
+were	O
+also	O
+obtained	O
+with	O
+a	O
+HepG2	O
+hepatoblastoma	O
+cell	O
+line	O
+carrying	O
+wt	B-GENE
+p53	I-GENE
+.	O
+
+Partial	O
+sequencing	O
+of	O
+the	O
+region	O
+downstream	O
+of	O
+ORF	B-GENE
+-	I-GENE
+Pto	I-GENE
+revealed	O
+homology	O
+to	O
+the	O
+ru	B-GENE
+/	I-GENE
+AB	I-GENE
+genes	I-GENE
+,	O
+involved	O
+in	O
+UV	O
+resistance	O
+,	O
+from	O
+plasmid	O
+pPSR1	O
+.	O
+
+The	O
+MSY2	B-GENE
+associated	O
+kinase	O
+is	O
+not	O
+casein	B-GENE
+kinase	I-GENE
+2	I-GENE
+,	O
+the	O
+kinase	O
+believed	O
+to	O
+phosphorylate	O
+mRNP3	B-GENE
++	I-GENE
+4	I-GENE
+in	O
+oocytes	O
+,	O
+but	O
+a	O
+yet	O
+unidentified	O
+kinase	O
+.	O
+
+This	O
+suggests	O
+that	O
+helicase	B-GENE
+-	I-GENE
+like	I-GENE
+genes	I-GENE
+may	O
+be	O
+involved	O
+in	O
+the	O
+biosynthesis	O
+of	O
+nucleic	O
+acids	O
+and	O
+proteins	O
+,	O
+and	O
+that	O
+the	O
+genes	O
+can	O
+be	O
+transcriptionally	O
+activated	O
+by	O
+heat	O
+shock	O
+to	O
+compensate	O
+for	O
+the	O
+repressed	O
+synthesis	O
+of	O
+mRNA	O
+and	O
+protein	O
+.	O
+
+These	O
+data	O
+provide	O
+the	O
+molecular	O
+tools	O
+for	O
+the	O
+final	O
+identification	O
+of	O
+the	O
+MKS	B-GENE
+and	O
+the	O
+MUL	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+origins	O
+of	O
+reflected	O
+light	O
+changes	O
+associated	O
+with	O
+neuronal	O
+activity	O
+(	O
+optical	O
+signals	O
+)	O
+were	O
+investigated	O
+in	O
+rat	O
+somatosensory	O
+cortex	O
+with	O
+optical	O
+imaging	O
+,	O
+microspectrophotometry	O
+,	O
+and	O
+laser	O
+-	O
+Doppler	O
+flowmetry	O
+,	O
+and	O
+dynamic	O
+changes	O
+in	O
+local	O
+hemoglobin	B-GENE
+concentration	O
+and	O
+oxygenation	O
+were	O
+focused	O
+on	O
+.	O
+
+Human	B-GENE
+neuronal	I-GENE
+Elav	I-GENE
+-	I-GENE
+like	I-GENE
+proteins	I-GENE
+contain	O
+three	O
+RNP	O
+-	O
+type	O
+RNA	O
+recognition	O
+motifs	O
+(	O
+RRMs	O
+)	O
+.	O
+
+Comparison	O
+of	O
+frequencies	O
+of	O
+atrial	O
+fibrillation	O
+after	O
+coronary	O
+artery	O
+bypass	O
+grafting	O
+with	O
+and	O
+without	O
+the	O
+use	O
+of	O
+cardiopulmonary	O
+bypass	O
+.	O
+
+The	O
+results	O
+of	O
+supershift	O
+analysis	O
+using	O
+specific	O
+antibodies	O
+against	O
+transcription	O
+factors	O
+suggested	O
+that	O
+both	O
+binding	O
+complexes	O
+contained	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+components	O
+p50	B-GENE
+and	O
+p65	B-GENE
+,	O
+and	O
+did	O
+not	O
+contain	O
+other	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+proteins	I-GENE
+(	O
+p52	B-GENE
+,	O
+c	B-GENE
+-	I-GENE
+Rel	I-GENE
+,	O
+Rel	B-GENE
+B	I-GENE
+)	O
+,	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+proteins	I-GENE
+(	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+,	O
+C	B-GENE
+-	I-GENE
+Jun	I-GENE
+)	O
+,	O
+CREB	B-GENE
+or	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+(	O
+NF	B-GENE
+-	I-GENE
+IL6	I-GENE
+)	O
+.	O
+
+A	O
+set	O
+of	O
+peptides	O
+corresponding	O
+to	O
+the	O
+individual	O
+elements	O
+of	O
+secondary	O
+structure	O
+derived	O
+from	O
+the	O
+N	O
+-	O
+terminal	O
+domain	O
+of	O
+the	O
+ribosomal	B-GENE
+protein	I-GENE
+L9	I-GENE
+have	O
+been	O
+synthesized	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+stimulated	O
+the	O
+rapid	O
+accumulation	O
+of	O
+interferon	B-GENE
+regulated	I-GENE
+factor	I-GENE
+(	I-GENE
+IRF	I-GENE
+)	I-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+,	O
+followed	O
+by	O
+a	O
+delayed	O
+and	O
+dose	O
+-	O
+dependent	O
+inhibition	O
+of	O
+alpha1	B-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+procollagen	I-GENE
+mRNA	I-GENE
+expression	O
+in	O
+skin	O
+fibroblasts	O
+from	O
+several	O
+different	O
+donors	O
+.	O
+
+Functional	O
+domains	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+promoter	I-GENE
+binding	I-GENE
+protein	I-GENE
+1	I-GENE
+involved	O
+in	O
+transcriptional	O
+repression	O
+and	O
+cell	O
+growth	O
+regulation	O
+.	O
+
+Therefore	O
+,	O
+we	O
+have	O
+named	O
+this	O
+gene	O
+UBP43	B-GENE
+.	O
+
+These	O
+results	O
+continue	O
+to	O
+support	O
+the	O
+hypothesis	O
+that	O
+HS2	O
+,	O
+HS3	O
+,	O
+and	O
+HS4	O
+act	O
+as	O
+a	O
+single	O
+,	O
+integral	O
+unit	O
+to	O
+regulate	O
+human	B-GENE
+globin	I-GENE
+gene	I-GENE
+transcription	O
+as	O
+a	O
+holocomplex	O
+,	O
+but	O
+they	O
+can	O
+also	O
+be	O
+interpreted	O
+to	O
+say	O
+that	O
+formation	O
+of	O
+a	O
+DNase	B-GENE
+I	I-GENE
+hypersensitive	O
+holocomplex	O
+alone	O
+is	O
+not	O
+sufficient	O
+for	O
+mediating	O
+high	O
+-	O
+level	O
+globin	B-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+Because	O
+there	O
+is	O
+great	O
+need	O
+for	O
+iron	O
+in	O
+the	O
+EPO	B-GENE
+-	O
+stimulated	O
+erythroid	O
+progenitors	O
+,	O
+it	O
+is	O
+essential	O
+that	O
+serum	B-GENE
+ferritin	I-GENE
+and	O
+transferrin	B-GENE
+saturation	O
+levels	O
+should	O
+be	O
+maintained	O
+over	O
+300	O
+microg	O
+/	O
+liter	O
+and	O
+30	O
+%	O
+,	O
+respectively	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+the	O
+p33	B-GENE
+subunit	I-GENE
+of	O
+eIF3	B-GENE
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+initiation	O
+phase	O
+of	O
+protein	O
+synthesis	O
+and	O
+that	O
+its	O
+RNA	O
+-	O
+binding	O
+domain	O
+is	O
+required	O
+for	O
+optimal	O
+activity	O
+.	O
+
+KEY	O
+WORDS	O
+:	O
+Melaleuca	O
+;	O
+Lake	O
+Okeechobee	O
+;	O
+Littoral	O
+zone	O
+;	O
+Water	O
+level	O
+;	O
+Regulation	O
+schedule	O
+
+The	O
+systolic	O
+peak	O
+of	O
+pulmonary	O
+vein	O
+was	O
+higher	O
+than	O
+the	O
+diastolic	O
+peak	O
+in	O
+45	O
+out	O
+of	O
+56	O
+cases	O
+.	O
+
+Specimens	O
+were	O
+assayed	O
+for	O
+alpha	B-GENE
+-	I-GENE
+fetoprotein	I-GENE
+,	O
+unconjugated	O
+estriol	O
+,	O
+free	O
+alpha	B-GENE
+hCG	I-GENE
+,	O
+and	O
+total	O
+hCG	B-GENE
+.	O
+
+The	O
+following	O
+data	O
+were	O
+recorded	O
+at	O
+arrival	O
+in	O
+the	O
+intensive	O
+care	O
+unit	O
+6	O
+,	O
+12	O
+,	O
+24	O
+,	O
+and	O
+48	O
+hours	O
+after	O
+termination	O
+of	O
+CPB	O
+:	O
+heart	O
+rate	O
+,	O
+blood	O
+pressure	O
+,	O
+left	O
+atrial	O
+pressure	O
+,	O
+central	O
+-	O
+peripheral	O
+temperature	O
+difference	O
+,	O
+arterial	O
+-	O
+central	O
+venous	O
+oxygen	O
+saturation	O
+difference	O
+,	O
+urine	O
+output	O
+,	O
+serum	O
+creatinine	O
+,	O
+lactate	O
+and	O
+neutrophil	B-GENE
+elastase	I-GENE
+levels	O
+,	O
+the	O
+Doppler	O
+echocardiographic	O
+factors	O
+shortening	O
+fraction	O
+and	O
+preejection	O
+period	O
+/	O
+left	O
+-	O
+ventricular	O
+ejection	O
+time	O
+,	O
+and	O
+cumulative	O
+doses	O
+of	O
+catecholamines	O
+(	O
+epinephrine	O
+)	O
+,	O
+enoximone	O
+,	O
+and	O
+furosemide	O
+.	O
+
+MDS1	B-GENE
+/	O
+EVI1	B-GENE
+,	O
+located	O
+on	O
+chromosome	O
+3	O
+band	O
+q26	O
+,	O
+encodes	O
+a	O
+zinc	B-GENE
+-	I-GENE
+finger	I-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+transcription	I-GENE
+activator	I-GENE
+not	O
+detected	O
+in	O
+normal	O
+hematopoietic	O
+cells	O
+but	O
+expressed	O
+in	O
+several	O
+normal	O
+tissues	O
+.	O
+
+The	O
+JTc	O
+delta	O
+among	O
+the	O
+three	O
+groups	O
+did	O
+not	O
+differ	O
+as	O
+well	O
+:	O
+JTc	O
+delta	O
+of	O
+the	O
+VT	O
+group	O
+was	O
+70	O
+ms	O
++	O
+/	O
+-	O
+30	O
+ms	O
+,	O
+the	O
+JTc	O
+delta	O
+of	O
+the	O
+PVC	O
+group	O
+was	O
+60	O
+msec	O
++	O
+/	O
+-	O
+25	O
+msec	O
+,	O
+and	O
+the	O
+JTc	O
+delta	O
+of	O
+the	O
+control	O
+group	O
+was	O
+70	O
+ms	O
++	O
+/	O
+-	O
+30	O
+ms	O
+.	O
+
+In	O
+contrast	O
+,	O
+deletion	O
+of	O
+the	O
+upstream	O
+portion	O
+of	O
+the	O
+delta	O
+promoter	O
+led	O
+to	O
+a	O
+10	O
+fold	O
+decrease	O
+in	O
+expression	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+of	O
+binding	O
+sites	O
+for	O
+the	O
+repressor	B-GENE
+proteins	I-GENE
+BP1	I-GENE
+and	O
+BP2	B-GENE
+in	O
+the	O
+upstream	O
+portion	O
+of	O
+the	O
+beta	B-GENE
+globin	I-GENE
+gene	I-GENE
+flanking	I-GENE
+region	I-GENE
+led	O
+to	O
+a	O
+4	O
+-	O
+6	O
+fold	O
+increase	O
+in	O
+promoter	O
+activity	O
+.	O
+
+However	O
+,	O
+with	O
+the	O
+alpha1	O
+antagonist	O
+prazosin	O
+(	O
+5	O
+x	O
+10	O
+(	O
+-	O
+8	O
+)	O
+-	O
+5	O
+x	O
+10	O
+(	O
+-	O
+7	O
+)	O
+M	O
+)	O
+,	O
+no	O
+relaxation	O
+occurred	O
+.	O
+
+Differential	O
+expression	O
+of	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+2beta	I-GENE
+in	O
+the	O
+developing	O
+chick	O
+retina	O
+:	O
+repression	O
+of	O
+R	B-GENE
+-	I-GENE
+FABP	I-GENE
+promoter	I-GENE
+activity	O
+by	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+The	O
+mean	O
+value	O
+of	O
+the	O
+CD79b	B-GENE
+to	O
+the	O
+CD79b	B-GENE
+internally	O
+deleted	O
+ratio	O
+was	O
+0	O
+.	O
+64	O
++	O
+/	O
+-	O
+0	O
+.	O
+20	O
+SD	O
+in	O
+normal	O
+donors	O
+and	O
+0	O
+.	O
+44	O
++	O
+/	O
+-	O
+0	O
+.	O
+27	O
+SD	O
+in	O
+B	O
+-	O
+CLL	O
+(	O
+P	O
+=	O
+.	O
+01	O
+)	O
+.	O
+
+As	O
+normal	O
+B	O
+cells	O
+also	O
+present	O
+this	O
+variant	O
+,	O
+the	O
+mechanism	O
+of	O
+CD79b	B-GENE
+posttranscriptional	O
+regulation	O
+might	O
+reflect	O
+the	O
+activation	O
+stage	O
+of	O
+the	O
+normal	O
+B	O
+cell	O
+from	O
+which	O
+B	O
+-	O
+CLL	O
+derives	O
+.	O
+
+High	O
+-	O
+level	O
+gains	O
+(	O
+HLGs	O
+)	O
+indicative	O
+of	O
+gene	O
+amplifications	O
+were	O
+identified	O
+at	O
+11q13	O
+in	O
+two	O
+cases	O
+,	O
+and	O
+in	O
+one	O
+case	O
+each	O
+at	O
+2q33	O
+-	O
+34	O
+,	O
+3q25	O
+-	O
+29	O
+,	O
+5p15	O
+.	O
+1	O
+-	O
+15	O
+.	O
+2	O
+,	O
+7q21	O
+-	O
+22	O
+,	O
+11p11	O
+.	O
+2	O
+,	O
+12p11	O
+.	O
+2	O
+-	O
+12	O
+,	O
+and	O
+13q34	O
+.	O
+
+With	O
+respect	O
+to	O
+the	O
+distribution	O
+of	O
+active	O
+MREs	O
+over	O
+the	O
+promoter	O
+region	O
+,	O
+the	O
+hMT	B-GENE
+-	I-GENE
+IIA	I-GENE
+gene	I-GENE
+is	O
+largely	O
+different	O
+from	O
+the	O
+mouse	O
+metallothionein	B-GENE
+-	I-GENE
+I	I-GENE
+gene	I-GENE
+,	O
+suggesting	O
+that	O
+MRE	O
+arrangement	O
+is	O
+not	O
+an	O
+important	O
+factor	O
+for	O
+metal	O
+regulation	O
+.	O
+
+The	O
+cDNA	O
+was	O
+expressed	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+under	O
+the	O
+control	O
+of	O
+the	O
+yeast	B-GENE
+triose	I-GENE
+phosphate	I-GENE
+isomerase	I-GENE
+promoter	I-GENE
+.	O
+
+Interestingly	O
+,	O
+the	O
+RNA	O
+sequences	O
+selected	O
+by	O
+the	O
+mutated	O
+zinc	B-GENE
+knuckle	I-GENE
+9G8	I-GENE
+variant	I-GENE
+are	O
+efficiently	O
+recognized	O
+by	O
+SRp20	B-GENE
+,	O
+in	O
+agreement	O
+with	O
+the	O
+fact	O
+that	O
+the	O
+RBD	O
+of	O
+9G8	B-GENE
+and	O
+SRp20	B-GENE
+are	O
+similar	O
+.	O
+
+Topoisomerase	B-GENE
+II	I-GENE
+is	O
+a	O
+major	O
+target	O
+of	O
+the	O
+protein	B-GENE
+kinase	I-GENE
+casein	I-GENE
+kinase	I-GENE
+2	I-GENE
+(	O
+PK	B-GENE
+CK2	I-GENE
+)	O
+in	O
+vivo	O
+.	O
+
+Recent	O
+work	O
+in	O
+this	O
+laboratory	O
+has	O
+shown	O
+that	O
+the	O
+gene	O
+coding	O
+for	O
+acetate	B-GENE
+kinase	I-GENE
+(	O
+ackA	B-GENE
+)	O
+in	O
+Sinorhizobium	O
+meliloti	O
+is	O
+up	O
+-	O
+regulated	O
+in	O
+response	O
+to	O
+phosphate	O
+limitation	O
+.	O
+
+All	O
+numbers	O
+refer	O
+to	O
+nucleotide	O
+positions	O
+on	O
+the	O
+wild	O
+-	O
+type	O
+HIV	O
+-	O
+1	O
+transcript	O
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+the	O
+complete	O
+structure	O
+of	O
+the	O
+human	B-GENE
+topoisomerase	I-GENE
+IIalpha	I-GENE
+gene	I-GENE
+,	O
+which	O
+consists	O
+of	O
+35	O
+exons	O
+spanning	O
+27	O
+.	O
+5	O
+kb	O
+.	O
+
+Previous	O
+studies	O
+characterized	O
+a	O
+cytokine	O
+-	O
+inducible	O
+,	O
+functional	O
+nuclear	B-GENE
+factor	I-GENE
+(	I-GENE
+NF	I-GENE
+)	I-GENE
+-	I-GENE
+kappaB	I-GENE
+consensus	I-GENE
+element	I-GENE
+in	O
+the	O
+immediate	O
+5	O
+'	O
+regulatory	O
+region	O
+of	O
+the	O
+MGSA	B-GENE
+/	O
+GRO	B-GENE
+-	I-GENE
+alpha	I-GENE
+gene	O
+at	O
+-	O
+78	O
+bp	O
+.	O
+
+An	O
+exon	O
+that	O
+prevents	O
+transport	O
+of	O
+a	O
+mature	O
+mRNA	O
+.	O
+
+Four	O
+CsA	O
+-	O
+treated	O
+patients	O
+developed	O
+persistently	O
+elevated	O
+UAER	O
+>	O
+30	O
+mg	O
+/	O
+24	O
+h	O
+(	O
+n	O
+=	O
+3	O
+with	O
+microalbuminuria	O
+)	O
+,	O
+whereas	O
+all	O
+the	O
+17	O
+placebo	O
+-	O
+treated	O
+patients	O
+had	O
+normal	O
+UAER	O
+(	O
+<	O
+30	O
+mg	O
+/	O
+24	O
+h	O
+)	O
+after	O
+7	O
+years	O
+of	O
+follow	O
+-	O
+up	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+the	O
+-	O
+84	O
+/	O
+-	O
+55	O
+DNA	O
+showed	O
+that	O
+JEG	O
+-	O
+3	O
+nuclear	O
+proteins	O
+bound	O
+to	O
+a	O
+site	O
+containing	O
+,	O
+but	O
+not	O
+identical	O
+to	O
+,	O
+the	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+sequence	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+no	O
+change	O
+was	O
+detected	O
+in	O
+the	O
+phenotype	O
+of	O
+'	O
+unstressed	O
+'	O
+clones	O
+,	O
+with	O
+respect	O
+to	O
+any	O
+of	O
+the	O
+following	O
+parameters	O
+:	O
+proliferation	O
+rate	O
+in	O
+monolayer	O
+,	O
+serum	O
+-	O
+dependence	O
+for	O
+proliferation	O
+or	O
+survival	O
+,	O
+tumorigenicity	O
+,	O
+cellular	O
+morphology	O
+,	O
+or	O
+tissue	O
+-	O
+specific	O
+differentiation	O
+markers	O
+.	O
+
+A	O
+high	O
+reactor	O
+pH	O
+(	O
++	O
+/	O
+-	O
+8	O
+)	O
+,	O
+a	O
+short	O
+solid	O
+retention	O
+time	O
+(	O
+<	O
+150	O
+days	O
+)	O
+,	O
+and	O
+the	O
+presence	O
+of	O
+a	O
+substantial	O
+SRB	O
+population	O
+in	O
+the	O
+inoculum	O
+may	O
+considerably	O
+reduce	O
+the	O
+time	O
+required	O
+for	O
+acetate	O
+-	O
+utilising	O
+SRB	O
+to	O
+outcompete	O
+MB	O
+.	O
+
+In	O
+throttling	O
+valves	O
+,	O
+the	O
+aim	O
+is	O
+to	O
+correlate	O
+the	O
+effect	O
+of	O
+shear	O
+to	O
+a	O
+parameter	O
+related	O
+to	O
+the	O
+inner	O
+geometry	O
+of	O
+the	O
+valve	O
+and	O
+to	O
+operating	O
+conditions	O
+.	O
+
+A	O
+mutation	O
+linked	O
+to	O
+the	O
+SOC1	B-GENE
+gene	I-GENE
+,	O
+previously	O
+defined	O
+by	O
+recessive	O
+mutations	O
+that	O
+suppress	O
+cbp1	B-GENE
+ts	I-GENE
+alleles	I-GENE
+and	O
+stabilize	O
+many	O
+mitochondrial	O
+mRNAs	O
+,	O
+was	O
+also	O
+isolated	O
+.	O
+
+A	O
+deletion	O
+mutation	O
+analysis	O
+of	O
+the	O
+recombinant	O
+protein	O
+has	O
+shown	O
+that	O
+the	O
+N	O
+-	O
+terminal	O
+region	O
+and	O
+the	O
+two	O
+leucine	O
+zippers	O
+are	O
+necessary	O
+for	O
+the	O
+binding	O
+.	O
+
+A	O
+database	O
+search	O
+has	O
+revealed	O
+as	O
+the	O
+most	O
+significative	O
+homology	O
+a	O
+match	O
+with	O
+the	O
+human	B-GENE
+mitochondrial	I-GENE
+transcription	I-GENE
+termination	I-GENE
+factor	I-GENE
+(	O
+mTERF	B-GENE
+)	O
+,	O
+a	O
+protein	O
+that	O
+also	O
+binds	O
+DNA	O
+as	O
+a	O
+monomer	O
+and	O
+contains	O
+three	O
+leucine	O
+zippers	O
+forming	O
+intramolecular	O
+interactions	O
+.	O
+
+In	O
+all	O
+trials	O
+,	O
+antigen	O
+challenge	O
+followed	O
+1	O
+h	O
+after	O
+the	O
+last	O
+treatment	O
+.	O
+
+31	O
+,	O
+1997	O
+,	O
+40	O
+patients	O
+had	O
+died	O
+(	O
+35	O
+in	O
+the	O
+ERA	O
+-	O
+II	O
+group	O
+and	O
+5	O
+in	O
+the	O
+ERA	O
+-	O
+III	O
+group	O
+)	O
+,	O
+for	O
+a	O
+crude	O
+mortality	O
+rate	O
+of	O
+8	O
+.	O
+0	O
+%	O
+.	O
+
+We	O
+found	O
+that	O
+total	O
+PSA	B-GENE
+can	O
+be	O
+detected	O
+in	O
+all	O
+cyst	O
+fluids	O
+and	O
+in	O
+about	O
+75	O
+%	O
+of	O
+female	O
+sera	O
+.	O
+
+Type	O
+I	O
+cysts	O
+(	O
+with	O
+a	O
+high	O
+K	O
++	O
+/	O
+Na	O
++	O
+ratio	O
+)	O
+tend	O
+to	O
+have	O
+higher	O
+total	O
+PSA	B-GENE
+than	O
+Type	O
+II	O
+cysts	O
+.	O
+
+Despite	O
+this	O
+DNA	O
+binding	O
+activity	O
+,	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+reporter	I-GENE
+activity	O
+was	O
+suppressed	O
+in	O
+these	O
+cells	O
+.	O
+
+A	O
+single	O
+N	O
+-	O
+glycosylation	O
+site	O
+present	O
+in	O
+chicken	B-GENE
+gp42	I-GENE
+is	O
+conserved	O
+among	O
+all	O
+five	O
+of	O
+these	O
+proteins	O
+:	O
+carbohydrate	O
+analysis	O
+of	O
+gp42	B-GENE
+revealed	O
+the	O
+presence	O
+of	O
+a	O
+complex	O
+type	O
+glycan	O
+chain	O
+at	O
+this	O
+site	O
+.	O
+
+Here	O
+we	O
+describe	O
+the	O
+optimization	O
+and	O
+characterization	O
+of	O
+a	O
+140	O
+-	O
+residue	O
+fragment	O
+,	O
+containing	O
+the	O
+Runt	B-GENE
+domain	I-GENE
+of	O
+AML1	B-GENE
+,	O
+which	O
+is	O
+suitable	O
+for	O
+structural	O
+studies	O
+.	O
+
+Judge	O
+OKs	O
+docs	O
+'	O
+bid	O
+for	O
+Chicago	O
+hospital	O
+.	O
+
+HANYS	O
+criticizes	O
+laparoscopic	O
+gall	O
+bladder	O
+guidelines	O
+.	O
+
+Groups	O
+dicker	O
+for	O
+price	O
+breaks	O
+as	O
+anesthetic	O
+gas	O
+goes	O
+multi	O
+-	O
+source	O
+.	O
+
+Troubled	O
+CareNetwork	O
+gets	O
+pact	O
+from	O
+largest	O
+teacher	O
+union	O
+in	O
+Wis	O
+.	O
+
+Ultrasonography	O
+provides	O
+excellent	O
+intraoperative	O
+evaluation	O
+of	O
+spinal	O
+cord	O
+injury	O
+.	O
+
+UPMC	O
+is	O
+not	O
+the	O
+only	O
+organization	O
+pursuing	O
+controlled	O
+NHBC	O
+organ	O
+procurement	O
+,	O
+however	O
+.	O
+
+Because	O
+of	O
+concerns	O
+regarding	O
+blood	O
+transfusion	O
+-	O
+related	O
+communicable	O
+disease	O
+(	O
+eg	O
+,	O
+acquired	O
+immune	O
+deficiency	O
+syndrome	O
+and	O
+non	O
+-	O
+A	O
+,	O
+non	O
+-	O
+B	O
+hepatitis	O
+)	O
+,	O
+there	O
+has	O
+been	O
+increasing	O
+research	O
+effort	O
+into	O
+postoperative	O
+hemorrhage	O
+related	O
+to	O
+cardiopulmonary	O
+bypass	O
+with	O
+extracorporeal	O
+circulation	O
+.	O
+
+They	O
+contrast	O
+trends	O
+in	O
+fertility	O
+,	O
+life	O
+expectancy	O
+ratios	O
+,	O
+and	O
+gender	O
+differences	O
+in	O
+these	O
+countries	O
+with	O
+the	O
+Hispanic	O
+population	O
+of	O
+the	O
+United	O
+States	O
+.	O
+
+Holger	O
+v	O
+.	O
+
+Hospital	O
+hit	O
+for	O
+hiring	O
+AHERF	O
+physicians	O
+.	O
+
+Overexpression	O
+of	O
+either	O
+DAP	B-GENE
+-	I-GENE
+1	I-GENE
+or	O
+sentrin	B-GENE
+causes	O
+apoptosis	O
+of	O
+TNF	B-GENE
+-	O
+sensitive	O
+L929	O
+fibroblast	O
+cell	O
+line	O
+,	O
+as	O
+well	O
+as	O
+TNF	B-GENE
+-	O
+resistant	O
+osteosarcoma	O
+cell	O
+line	O
+,	O
+U2OS	O
+.	O
+
+This	O
+is	O
+in	O
+contrast	O
+to	O
+PPARgamma2	B-GENE
+,	O
+which	O
+was	O
+previously	O
+shown	O
+to	O
+be	O
+phosphorylated	O
+at	O
+a	O
+single	O
+site	O
+in	O
+a	O
+motif	O
+that	O
+is	O
+not	O
+homologous	O
+to	O
+the	O
+sites	O
+now	O
+described	O
+in	O
+PPARalpha	B-GENE
+.	O
+
+These	O
+results	O
+suggest	O
+KCC3	B-GENE
+is	O
+a	O
+new	O
+member	O
+of	O
+the	O
+KCC	B-GENE
+family	I-GENE
+that	O
+is	O
+under	O
+distinct	O
+regulation	O
+from	O
+KCC1	B-GENE
+.	O
+
+We	O
+have	O
+screened	O
+the	O
+elastin	B-GENE
+gene	I-GENE
+for	O
+mutations	O
+responsible	O
+for	O
+supravalvular	O
+aortic	O
+stenosis	O
+(	O
+SVAS	O
+)	O
+in	O
+two	O
+large	O
+,	O
+independently	O
+collected	O
+families	O
+with	O
+isolated	O
+(	O
+nonsyndromic	O
+)	O
+SVAS	O
+.	O
+
+Spatiotemporal	O
+expression	O
+of	O
+the	O
+PAX3	B-GENE
+gene	I-GENE
+is	O
+tightly	O
+regulated	O
+during	O
+development	O
+.	O
+
+A	O
+list	O
+of	O
+12	O
+names	O
+for	O
+the	O
+disease	O
+and	O
+37	O
+diagnostic	O
+criteria	O
+were	O
+proposed	O
+to	O
+a	O
+Consensus	O
+Panel	O
+of	O
+12	O
+Italian	O
+experts	O
+who	O
+ranked	O
+them	O
+in	O
+order	O
+so	O
+as	O
+to	O
+identify	O
+a	O
+core	O
+set	O
+of	O
+criteria	O
+.	O
+
+Methanesulfonyl	O
+fluoride	O
+(	O
+MSF	O
+)	O
+:	O
+a	O
+double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+study	O
+of	O
+safety	O
+and	O
+efficacy	O
+in	O
+the	O
+treatment	O
+of	O
+senile	O
+dementia	O
+of	O
+the	O
+Alzheimer	O
+type	O
+.	O
+
+METHODS	O
+:	O
+Between	O
+August	O
+1991	O
+and	O
+June	O
+1994	O
+,	O
+198	O
+men	O
+with	O
+clinical	O
+T2	O
+or	O
+T3	O
+classified	O
+(	O
+TNM	O
+)	O
+prostate	O
+carcinoma	O
+(	O
+bone	O
+scan	O
+negative	O
+)	O
+who	O
+were	O
+at	O
+high	O
+risk	O
+of	O
+lymph	O
+node	O
+involvement	O
+underwent	O
+a	O
+111In	O
+-	O
+capromab	O
+pendetide	O
+scan	O
+prior	O
+to	O
+staging	O
+lymphadenectomy	O
+.	O
+
+Voluntary	O
+wheel	O
+running	O
+did	O
+not	O
+significantly	O
+increase	O
+estimated	O
+alanine	O
+or	O
+pyruvate	O
+Gneo	O
+or	O
+absolute	O
+glycerol	O
+Ra	O
+.	O
+
+Immediately	O
+after	O
+surgery	O
+,	O
+dialysate	O
+PGE2	O
+and	O
+adenosine	O
+concentrations	O
+were	O
+3	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+and	O
+296	O
++	O
+/	O
+-	O
+127	O
+nM	O
+,	O
+respectively	O
+.	O
+
+Because	O
+of	O
+the	O
+probable	O
+causal	O
+relationship	O
+between	O
+constitutive	O
+p210	B-GENE
+(	O
+bcr	B-GENE
+/	O
+abl	B-GENE
+)	O
+protein	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+activity	O
+and	O
+manifestations	O
+of	O
+chronic	O
+-	O
+phase	O
+chronic	O
+myelogenous	O
+leukemia	O
+(	O
+CML	O
+;	O
+myeloid	O
+expansion	O
+)	O
+,	O
+a	O
+key	O
+goal	O
+is	O
+to	O
+identify	O
+relevant	O
+p210	B-GENE
+substrates	O
+in	O
+primary	O
+chronic	O
+-	O
+phase	O
+CML	O
+hematopoietic	O
+progenitor	O
+cells	O
+.	O
+
+In	O
+vitro	O
+precipitation	O
+with	O
+a	O
+glutathione	B-GENE
+-	I-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+-	I-GENE
+fusion	I-GENE
+protein	I-GENE
+containing	O
+the	O
+C	O
+-	O
+terminal	O
+transactivation	O
+domain	O
+of	O
+STAT5a	B-GENE
+showed	O
+GH	B-GENE
+-	O
+regulated	O
+association	O
+of	O
+ERK1	B-GENE
+/	I-GENE
+2	I-GENE
+with	O
+the	O
+fusion	O
+protein	O
+,	O
+while	O
+this	O
+was	O
+not	O
+seen	O
+when	O
+serine	O
+780	O
+in	O
+STAT5a	B-GENE
+was	O
+changed	O
+to	O
+alanine	O
+.	O
+
+One	O
+such	O
+element	O
+,	O
+1P	O
+,	O
+was	O
+employed	O
+to	O
+clone	O
+from	O
+a	O
+rat	O
+pituitary	O
+cDNA	O
+expression	O
+library	O
+a	O
+novel	O
+417	B-GENE
+-	I-GENE
+amino	I-GENE
+acid	I-GENE
+WD	I-GENE
+protein	I-GENE
+,	O
+designated	O
+PREB	B-GENE
+(	I-GENE
+PRL	I-GENE
+regulatory	I-GENE
+element	I-GENE
+binding	I-GENE
+)	I-GENE
+protein	I-GENE
+.	O
+
+Characterization	O
+of	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+MTF	I-GENE
+-	I-GENE
+1	I-GENE
+from	O
+the	O
+Japanese	O
+pufferfish	O
+(	O
+Fugu	O
+rubripes	O
+)	O
+reveals	O
+evolutionary	O
+conservation	O
+of	O
+heavy	O
+metal	O
+stress	O
+response	O
+.	O
+
+The	O
+peroxisome	B-GENE
+proliferator	I-GENE
+-	I-GENE
+activated	I-GENE
+receptors	I-GENE
+(	O
+PPARs	B-GENE
+)	O
+are	O
+members	O
+of	O
+the	O
+nuclear	B-GENE
+hormone	I-GENE
+receptor	I-GENE
+superfamily	I-GENE
+.	O
+
+However	O
+,	O
+F	B-GENE
+-	I-GENE
+SRC	I-GENE
+-	I-GENE
+1	I-GENE
+mutant	I-GENE
+lacking	O
+CBP	B-GENE
+-	I-GENE
+interacting	I-GENE
+domain	I-GENE
+still	O
+preserved	O
+enhancing	O
+activity	O
+.	O
+
+The	O
+catalytic	O
+site	O
+has	O
+an	O
+S1	O
+pocket	O
+lined	O
+with	O
+conserved	O
+hydrophobic	O
+residues	O
+to	O
+accommodate	O
+the	O
+pyroglutamyl	O
+residue	O
+.	O
+
+The	O
+complete	O
+circular	O
+TTV	O
+genome	O
+contained	O
+a	O
+novel	O
+sequence	O
+of	O
+113	O
+nt	O
+(	O
+nt	O
+3740	O
+to	O
+3852	O
+[	O
+=	O
+0	O
+]	O
+)	O
+in	O
+between	O
+the	O
+known	O
+3	O
+'	O
+-	O
+and	O
+5	O
+'	O
+-	O
+end	O
+arms	O
+,	O
+forming	O
+a	O
+117	O
+-	O
+nt	O
+GC	O
+-	O
+rich	O
+stretch	O
+(	O
+GC	O
+content	O
+,	O
+90	O
+.	O
+6	O
+%	O
+at	O
+nt	O
+3736	O
+to	O
+3852	O
+)	O
+.	O
+
+The	O
+Asian	O
+mouse	O
+Mus	O
+castaneus	O
+is	O
+resistant	O
+to	O
+infection	O
+by	O
+the	O
+polytropic	O
+mink	O
+cell	O
+focus	O
+-	O
+inducing	O
+(	O
+MCF	O
+)	O
+subgroup	O
+of	O
+murine	O
+leukemia	O
+viruses	O
+(	O
+MuLVs	O
+)	O
+.	O
+
+To	O
+determine	O
+the	O
+function	O
+of	O
+VZV	B-GENE
+gK	I-GENE
+in	O
+virus	O
+growth	O
+,	O
+a	O
+series	O
+of	O
+gK	B-GENE
+deletion	I-GENE
+mutants	I-GENE
+were	O
+constructed	O
+with	O
+VZV	O
+cosmid	O
+DNA	O
+derived	O
+from	O
+the	O
+Oka	O
+strain	O
+.	O
+
+CCAAT	B-GENE
+displacement	I-GENE
+protein	I-GENE
+binds	O
+to	O
+and	O
+negatively	O
+regulates	O
+human	O
+papillomavirus	O
+type	O
+6	O
+E6	B-GENE
+,	O
+E7	B-GENE
+,	O
+and	O
+E1	B-GENE
+promoters	O
+.	O
+
+Three	O
+different	O
+site	O
+-	O
+directed	O
+mutations	O
+of	O
+the	O
+cyclic	O
+AMP	O
+response	O
+element	O
+each	O
+reduced	O
+the	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+effect	O
+by	O
+>	O
+90	O
+%	O
+.	O
+
+Using	O
+an	O
+RNase	B-GENE
+H	I-GENE
+protection	O
+assay	O
+and	O
+specific	O
+blocking	O
+oligonucleotides	O
+,	O
+we	O
+find	O
+that	O
+recognition	O
+of	O
+the	O
+5	O
+'	O
+splice	O
+-	O
+site	O
+(	O
+5	O
+'	O
+ss	O
+)	O
+and	O
+branchpoint	O
+sequence	O
+(	O
+BPS	O
+)	O
+elements	O
+by	O
+U11	B-GENE
+and	O
+U12	B-GENE
+snRNPs	I-GENE
+,	O
+respectively	O
+,	O
+displays	O
+strong	O
+cooperativity	O
+,	O
+requiring	O
+both	O
+sites	O
+in	O
+the	O
+pre	O
+-	O
+mRNA	O
+substrate	O
+for	O
+efficient	O
+complex	O
+formation	O
+.	O
+
+Many	O
+eukaryotic	O
+cell	O
+surface	O
+proteins	O
+are	O
+anchored	O
+in	O
+the	O
+lipid	O
+bilayer	O
+through	O
+glycosylphosphatidylinositol	O
+(	O
+GPI	O
+)	O
+.	O
+
+An	O
+endogenous	O
+mammalian	O
+regulator	O
+of	O
+this	O
+process	O
+,	O
+named	O
+Usurpin	B-GENE
+,	O
+has	O
+been	O
+identified	O
+(	O
+aliases	O
+for	O
+Usurpin	B-GENE
+include	O
+CASH	B-GENE
+,	O
+Casper	B-GENE
+,	O
+CLARP	B-GENE
+,	O
+FLAME	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+FLIP	B-GENE
+,	O
+I	B-GENE
+-	I-GENE
+FLICE	I-GENE
+and	O
+MRIT	B-GENE
+)	O
+.	O
+
+Plasma	O
+glucose	O
+,	O
+immunoreactive	B-GENE
+insulin	I-GENE
+(	O
+IRI	B-GENE
+)	O
+,	O
+C	B-GENE
+-	I-GENE
+peptide	I-GENE
+,	O
+glucagon	B-GENE
+,	O
+and	O
+GLP	B-GENE
+-	I-GENE
+1	I-GENE
+levels	O
+at	O
+each	O
+time	O
+point	O
+during	O
+OGTT	O
+were	O
+measured	O
+.	O
+
+Technetium	O
+-	O
+99m	O
+methylene	O
+diphosphonate	O
+scintimammography	O
+for	O
+evaluation	O
+of	O
+palpable	O
+breast	O
+masses	O
+.	O
+
+Nuclear	O
+receptors	O
+(	O
+NRs	O
+)	O
+can	O
+function	O
+as	O
+ligandinducible	O
+transregulators	O
+in	O
+both	O
+mammalian	O
+and	O
+yeast	O
+cells	O
+,	O
+indicating	O
+that	O
+important	O
+features	O
+of	O
+transcriptional	O
+control	O
+have	O
+been	O
+conserved	O
+throughout	O
+evolution	O
+.	O
+
+When	O
+tethered	O
+to	O
+a	O
+heterologous	O
+DNA	O
+-	O
+binding	O
+domain	O
+,	O
+PSU1	B-GENE
+can	O
+activate	O
+transcription	O
+on	O
+its	O
+own	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+follow	O
+-	O
+up	O
+prospectively	O
+patients	O
+with	O
+arthritis	O
+after	O
+infection	O
+with	O
+beta	O
+-	O
+haemolytic	O
+streptococci	O
+of	O
+Lancefield	O
+group	O
+A	O
+(	O
+beta	O
+HSA	O
+)	O
+,	O
+with	O
+emphasis	O
+on	O
+clinical	O
+characteristics	O
+and	O
+serological	O
+features	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+expression	O
+of	O
+the	O
+protein	O
+was	O
+maximum	O
+in	O
+mitosis	O
+and	O
+minimum	O
+in	O
+G1	O
+,	O
+which	O
+correlated	O
+with	O
+the	O
+expression	O
+of	O
+its	O
+messenger	O
+RNA	O
+.	O
+
+These	O
+findings	O
+demonstrate	O
+that	O
+signature	O
+-	O
+tagged	O
+mutagenesis	O
+is	O
+a	O
+viable	O
+approach	O
+to	O
+identify	O
+bacterial	O
+genes	O
+associated	O
+with	O
+the	O
+ability	O
+to	O
+infect	O
+the	O
+urinary	O
+tract	O
+.	O
+
+Pathol	O
+.	O
+
+The	O
+eukaryotic	O
+cell	O
+cycle	O
+is	O
+governed	O
+in	O
+part	O
+by	O
+the	O
+periodic	O
+transcription	O
+of	O
+cyclin	B-GENE
+genes	I-GENE
+,	O
+whose	O
+protein	O
+products	O
+associate	O
+with	O
+and	O
+positively	O
+regulate	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+.	O
+
+The	O
+GAC1	B-GENE
+gene	I-GENE
+encodes	O
+the	O
+regulatory	O
+subunit	O
+for	O
+a	O
+type	B-GENE
+1	I-GENE
+serine	I-GENE
+/	I-GENE
+threonine	I-GENE
+phosphoprotein	I-GENE
+phosphatase	I-GENE
+,	O
+Glc7	B-GENE
+.	O
+
+The	O
+results	O
+demonstrate	O
+that	O
+the	O
+Glc7	B-GENE
+phosphatase	I-GENE
+and	O
+its	O
+Gac1	B-GENE
+regulatory	O
+subunit	O
+play	O
+positive	O
+roles	O
+in	O
+HSF	B-GENE
+activation	O
+of	O
+CUP1	B-GENE
+transcription	O
+.	O
+
+MEF	B-GENE
+and	O
+AML1B	B-GENE
+synergistically	O
+transactivated	O
+an	O
+interleukin	B-GENE
+3	I-GENE
+promoter	I-GENE
+reporter	I-GENE
+gene	I-GENE
+construct	I-GENE
+,	O
+yet	O
+the	O
+activating	O
+activity	O
+of	O
+MEF	B-GENE
+was	O
+abolished	O
+when	O
+MEF	B-GENE
+was	O
+coexpressed	O
+with	O
+AML1	B-GENE
+/	O
+ETO	B-GENE
+.	O
+
+Mechanistically	O
+,	O
+the	O
+presence	O
+of	O
+the	O
+GRR	O
+appears	O
+to	O
+stop	O
+further	O
+degradation	O
+of	O
+p50	B-GENE
+and	O
+to	O
+stabilize	O
+the	O
+molecule	O
+.	O
+
+This	O
+phosphorylation	O
+can	O
+be	O
+catalyzed	O
+by	O
+a	O
+break	O
+-	O
+ended	O
+double	O
+-	O
+stranded	O
+DNA	O
+-	O
+activated	O
+protein	O
+kinase	O
+activity	O
+from	O
+the	O
+sea	O
+urchin	O
+nucleus	O
+in	O
+vitro	O
+.	O
+
+Concomitantly	O
+,	O
+the	O
+total	O
+cellular	O
+level	O
+of	O
+p21	B-GENE
+increased	O
+severalfold	O
+via	O
+a	O
+posttranscriptional	O
+mechanism	O
+.	O
+
+Moreover	O
+,	O
+when	O
+added	O
+to	O
+the	O
+osteoclast	O
+cultures	O
+,	O
+mrIhh	B-GENE
+-	I-GENE
+N	I-GENE
+markedly	O
+stimulated	O
+the	O
+formation	O
+of	O
+resorption	O
+pits	O
+on	O
+dentine	O
+slices	O
+.	O
+
+Overall	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+resistant	O
+genotypes	O
+exist	O
+among	O
+the	O
+WAD	O
+goat	O
+population	O
+.	O
+
+The	O
+molecular	O
+mechanism	O
+by	O
+which	O
+Gle2p	B-GENE
+and	O
+the	O
+Gle2p	B-GENE
+-	O
+Nup116p	B-GENE
+interaction	O
+function	O
+in	O
+mRNA	O
+export	O
+is	O
+unknown	O
+.	O
+
+The	O
+Fyn	B-GENE
+NH2	I-GENE
+terminus	I-GENE
+was	O
+necessary	O
+but	O
+not	O
+sufficient	O
+for	O
+interaction	O
+with	O
+zeta	O
+and	O
+both	O
+Fyn	B-GENE
+kinase	I-GENE
+and	O
+SH2	B-GENE
+domains	I-GENE
+were	O
+required	O
+,	O
+directing	O
+phosphorylation	O
+of	O
+zeta	B-GENE
+ITAM	I-GENE
+tyrosines	O
+and	O
+binding	O
+to	O
+zeta	B-GENE
+ITAM	I-GENE
+phosphotyrosines	O
+.	O
+
+In	O
+budding	O
+yeast	O
+,	O
+the	O
+protein	O
+Skp1p	B-GENE
+,	O
+the	O
+cullin	B-GENE
+-	I-GENE
+family	I-GENE
+member	I-GENE
+Cdc53p	B-GENE
+,	O
+and	O
+the	O
+F	O
+-	O
+box	O
+/	O
+WD	O
+-	O
+repeat	O
+protein	O
+Cdc4p	B-GENE
+form	O
+the	O
+SCFCdc4p	B-GENE
+ubiquitin	B-GENE
+ligase	I-GENE
+complex	O
+,	O
+which	O
+targets	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+(	O
+Cdk	B-GENE
+)	O
+inhibitor	O
+Sic1p	B-GENE
+for	O
+proteolysis	O
+[	O
+3	O
+]	O
+[	O
+4	O
+]	O
+[	O
+5	O
+]	O
+[	O
+6	O
+]	O
+[	O
+7	O
+]	O
+[	O
+8	O
+]	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+,	O
+despite	O
+their	O
+structural	O
+and	O
+functional	O
+similarities	O
+,	O
+the	O
+pop1	B-GENE
+and	O
+pop2	B-GENE
+genes	I-GENE
+fail	O
+to	O
+complement	O
+each	O
+other	O
+'	O
+s	O
+deletion	O
+phenotypes	O
+,	O
+indicating	O
+that	O
+they	O
+perform	O
+non	O
+-	O
+redundant	O
+,	O
+but	O
+potentially	O
+interdependent	O
+,	O
+functions	O
+in	O
+proteolysis	O
+.	O
+
+Antithrombin	B-GENE
+III	I-GENE
+prevents	O
+60	O
+min	O
+warm	O
+intestinal	O
+ischemia	O
+reperfusion	O
+injury	O
+in	O
+rats	O
+.	O
+
+In	O
+retrospect	O
+,	O
+the	O
+diagnoses	O
+were	O
+reconsidered	O
+applying	O
+strict	O
+criteria	O
+.	O
+
+These	O
+observations	O
+of	O
+elevated	O
+serum	B-GENE
+lipase	I-GENE
+and	O
+serum	O
+CA	B-GENE
+19	I-GENE
+-	I-GENE
+9	I-GENE
+in	O
+Sjogren	O
+'	O
+s	O
+syndrome	O
+without	O
+evidence	O
+of	O
+malignancy	O
+may	O
+reflect	O
+pancreatic	O
+involvement	O
+in	O
+this	O
+disorder	O
+.	O
+
+Acute	O
+pancreatitis	O
+as	O
+a	O
+complication	O
+of	O
+polyarteritis	O
+nodosa	O
+.	O
+
+Significantly	O
+greater	O
+improvement	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+in	O
+the	O
+sertraline	O
+group	O
+first	O
+became	O
+apparent	O
+by	O
+the	O
+end	O
+of	O
+week	O
+3	O
+on	O
+the	O
+Y	O
+-	O
+BOCS	O
+and	O
+the	O
+CGI	O
+Improvement	O
+scale	O
+,	O
+and	O
+by	O
+the	O
+end	O
+of	O
+weeks	O
+6	O
+and	O
+8	O
+,	O
+respectively	O
+,	O
+on	O
+the	O
+NIMH	O
+and	O
+CGI	O
+Severity	O
+scale	O
+.	O
+
+Stress	B-GENE
+-	I-GENE
+inducible	I-GENE
+protein	I-GENE
+kinases	I-GENE
+capable	O
+of	O
+activating	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+expression	O
+include	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+/	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+SAPK	B-GENE
+/	O
+JNK	B-GENE
+)	O
+and	O
+p38	B-GENE
+members	O
+of	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+MAPK	B-GENE
+)	O
+superfamily	O
+of	O
+signaling	O
+molecules	O
+.	O
+
+Transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	I-GENE
+TGF	I-GENE
+)	I-GENE
+-	I-GENE
+beta1	I-GENE
+induces	O
+extracellular	O
+matrix	O
+deposition	O
+and	O
+proliferation	O
+of	O
+mesenchymal	O
+cells	O
+.	O
+
+Chronotherapeutics	O
+in	O
+cardiovascular	O
+disease	O
+.	O
+
+Group	O
+psychometric	O
+functions	O
+for	O
+listeners	O
+with	O
+hearing	O
+loss	O
+do	O
+not	O
+show	O
+a	O
+decrease	O
+in	O
+performance	O
+at	O
+the	O
+largest	O
+values	O
+of	O
+delta	O
+f	O
+included	O
+in	O
+this	O
+study	O
+.	O
+
+Uroflowmetry	O
+can	O
+detect	O
+dysuria	O
+,	O
+which	O
+may	O
+be	O
+poorly	O
+perceived	O
+or	O
+even	O
+unknown	O
+to	O
+the	O
+subjects	O
+themselves	O
+.	O
+
+Marked	O
+racial	O
+variation	O
+in	O
+birthweight	O
+percentiles	O
+by	O
+gestational	O
+age	O
+was	O
+evident	O
+.	O
+
+Significant	O
+correlations	O
+between	O
+mental	O
+status	O
+as	O
+measured	O
+by	O
+the	O
+Mini	O
+-	O
+Mental	O
+State	O
+Examination	O
+and	O
+NA	O
+/	O
+mI	O
+,	O
+mI	O
+/	O
+Cr	O
+and	O
+NA	O
+were	O
+found	O
+.	O
+
+Glucagon	B-GENE
+also	O
+induced	O
+LUC	B-GENE
+activity	O
+very	O
+strongly	O
+when	O
+the	O
+CRE1	O
+and	O
+CRE2	O
+sites	O
+were	O
+combined	O
+;	O
+induction	O
+of	O
+the	O
+(	O
+CRE1	O
+)	O
+3	O
+(	O
+CRE2	O
+)	O
+2SV40	O
+-	O
+LUC	B-GENE
+constructs	O
+was	O
+positively	O
+modulated	O
+by	O
+the	O
+pO2	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+report	O
+the	O
+isolation	O
+and	O
+characterization	O
+of	O
+the	O
+entire	O
+rat	B-GENE
+GSTA3	I-GENE
+(	O
+rGST	B-GENE
+Yc1	I-GENE
+)	O
+subunit	O
+gene	O
+.	O
+
+Calcinosis	O
+cutis	O
+following	O
+intravenous	O
+infusion	O
+of	O
+calcium	O
+gluconate	O
+.	O
+
+Finally	O
+,	O
+we	O
+determined	O
+the	O
+genomic	O
+organization	O
+of	O
+the	O
+human	B-GENE
+TrxR2	I-GENE
+gene	I-GENE
+,	O
+which	O
+consists	O
+of	O
+18	O
+exons	O
+spanning	O
+about	O
+67	O
+kb	O
+,	O
+and	O
+its	O
+chromosomal	O
+localization	O
+at	O
+position	O
+22q11	O
+.	O
+2	O
+.	O
+
+The	O
+aims	O
+of	O
+this	O
+study	O
+were	O
+to	O
+determine	O
+and	O
+rank	O
+the	O
+frequency	O
+of	O
+self	O
+reported	O
+visual	O
+disability	O
+in	O
+daily	O
+tasks	O
+performed	O
+by	O
+glaucoma	O
+patients	O
+;	O
+to	O
+examine	O
+the	O
+interrelation	O
+between	O
+disabilities	O
+using	O
+factor	O
+analysis	O
+;	O
+to	O
+study	O
+the	O
+relation	O
+between	O
+perceived	O
+visual	O
+difficulty	O
+and	O
+a	O
+measure	O
+of	O
+the	O
+severity	O
+of	O
+visual	O
+field	O
+loss	O
+;	O
+to	O
+develop	O
+a	O
+glaucoma	O
+specific	O
+subgroup	O
+of	O
+questions	O
+;	O
+and	O
+examine	O
+the	O
+validity	O
+and	O
+reliability	O
+of	O
+this	O
+subgroup	O
+of	O
+questions	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+validity	O
+of	O
+this	O
+new	O
+subset	O
+of	O
+questions	O
+was	O
+shown	O
+to	O
+be	O
+significant	O
+(	O
+r	O
+=	O
+0	O
+.	O
+037	O
+,	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+for	O
+the	O
+correlation	O
+between	O
+a	O
+measure	O
+of	O
+the	O
+severity	O
+of	O
+binocular	O
+visual	O
+field	O
+loss	O
+and	O
+the	O
+mean	O
+score	O
+of	O
+the	O
+variables	O
+used	O
+in	O
+the	O
+glaucoma	O
+specific	O
+subgroup	O
+of	O
+questions	O
+.	O
+
+Sequence	O
+comparison	O
+of	O
+cytochromes	B-GENE
+bd	I-GENE
+and	O
+their	O
+homologs	O
+from	O
+various	O
+organisms	O
+demonstrates	O
+that	O
+the	O
+proteins	O
+can	O
+be	O
+classified	O
+into	O
+two	O
+subfamilies	O
+,	O
+a	O
+proteobacterial	O
+type	O
+including	O
+E	B-GENE
+.	I-GENE
+coli	I-GENE
+bd	I-GENE
+and	O
+a	O
+more	O
+widely	O
+distributed	O
+type	O
+including	O
+the	O
+B	O
+.	O
+stearothermophilus	O
+enzyme	O
+,	O
+suggesting	O
+that	O
+the	O
+latter	O
+type	O
+is	O
+evolutionarily	O
+older	O
+.	O
+
+In	O
+11	O
+eyes	O
+that	O
+had	O
+been	O
+selected	O
+at	O
+random	O
+10	O
+micrograms	O
+of	O
+recombinant	B-GENE
+tissue	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+were	O
+injected	O
+midvitreally	O
+24	O
+hrs	O
+later	O
+.	O
+
+RESULTS	O
+AND	O
+CONCLUSIONS	O
+:	O
+Brandt	O
+'	O
+s	O
+double	O
+cuff	O
+-	O
+tubes	O
+(	O
+G2	O
+)	O
+succeed	O
+in	O
+avoiding	O
+uncontrolled	O
+increase	O
+of	O
+cuff	O
+-	O
+pressure	O
+during	O
+anaesthesia	O
+with	O
+N2O	O
+.	O
+
+Accordingly	O
+,	O
+we	O
+designated	O
+this	O
+gene	B-GENE
+CTL1	I-GENE
+(	O
+capping	B-GENE
+enzyme	I-GENE
+RNAtriphosphatase	I-GENE
+-	I-GENE
+like	I-GENE
+1	I-GENE
+)	O
+.	O
+
+Their	O
+afterglows	O
+are	O
+brighter	O
+than	O
+supernovae	O
+and	O
+therefore	O
+are	O
+called	O
+hypernovae	O
+.	O
+
+Constrictive	O
+pericarditis	O
+and	O
+pleuropulmonary	O
+disease	O
+linked	O
+to	O
+ergot	O
+dopamine	O
+agonist	O
+therapy	O
+(	O
+cabergoline	O
+)	O
+for	O
+Parkinson	O
+'	O
+s	O
+disease	O
+.	O
+
+An	O
+undilated	O
+type	O
+of	O
+APBD	O
+is	O
+frequently	O
+associated	O
+with	O
+AMT	O
+and	O
+we	O
+believe	O
+,	O
+therefore	O
+,	O
+that	O
+clinicians	O
+should	O
+be	O
+aware	O
+of	O
+a	O
+possible	O
+coexistence	O
+of	O
+APBD	O
+and	O
+AMT	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+also	O
+constructed	O
+and	O
+expressed	O
+chimeric	O
+fusion	O
+protein	O
+that	O
+contains	O
+HIV	B-GENE
+-	I-GENE
+2	I-GENE
+gag	I-GENE
+with	O
+V3	B-GENE
+domains	O
+of	O
+HIV	O
+-	O
+1IIIB	O
+,	O
+HIV	O
+-	O
+1MN	O
+,	O
+HIV	O
+-	O
+1SF2	O
+and	O
+HIV	O
+-	O
+1RF	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+V3	B-GENE
+peptides	O
+from	O
+all	O
+major	O
+clades	O
+of	O
+HIV	O
+-	O
+1	O
+carried	O
+by	O
+HIV	B-GENE
+-	I-GENE
+2	I-GENE
+gag	I-GENE
+can	O
+be	O
+used	O
+as	O
+a	O
+potential	O
+HIV	O
+/	O
+AIDS	O
+vaccine	O
+.	O
+
+Efficacy	O
+was	O
+determined	O
+by	O
+responses	O
+to	O
+question	O
+3	O
+(	O
+ability	O
+to	O
+achieve	O
+an	O
+erection	O
+)	O
+and	O
+question	O
+4	O
+(	O
+ability	O
+to	O
+maintain	O
+an	O
+erection	O
+)	O
+of	O
+the	O
+15	O
+-	O
+item	O
+International	O
+Index	O
+of	O
+Erectile	O
+Function	O
+(	O
+IIEF	O
+)	O
+.	O
+
+Evidence	O
+for	O
+the	O
+involvement	O
+of	O
+the	O
+Glc7	B-GENE
+-	O
+Reg1	B-GENE
+phosphatase	O
+and	O
+the	O
+Snf1	B-GENE
+-	O
+Snf4	B-GENE
+kinase	O
+in	O
+the	O
+regulation	O
+of	O
+INO1	B-GENE
+transcription	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+.	O
+
+In	O
+XO	O
+males	O
+,	O
+two	O
+her	B-GENE
+-	I-GENE
+1	I-GENE
+mRNAs	I-GENE
+,	O
+her	B-GENE
+-	I-GENE
+1a	I-GENE
+and	O
+her	B-GENE
+-	I-GENE
+1b	I-GENE
+,	O
+are	O
+transcribed	O
+from	O
+two	O
+separate	O
+promoters	O
+:	O
+P1	O
+,	O
+located	O
+in	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+,	O
+and	O
+P2	O
+,	O
+located	O
+in	O
+the	O
+large	O
+second	O
+intron	O
+.	O
+
+Induction	O
+of	O
+Fas	B-GENE
+ligand	I-GENE
+expression	O
+by	O
+HIV	O
+involves	O
+the	O
+interaction	O
+of	O
+Nef	B-GENE
+with	O
+the	O
+T	B-GENE
+cell	I-GENE
+receptor	I-GENE
+zeta	I-GENE
+chain	I-GENE
+.	O
+
+Receptor	B-GENE
+protein	I-GENE
+tyrosine	I-GENE
+phosphatases	I-GENE
+(	O
+RPTPs	B-GENE
+)	O
+comprise	O
+a	O
+family	O
+of	O
+proteins	O
+that	O
+feature	O
+intracellular	O
+phosphatase	O
+domains	O
+and	O
+an	O
+ectodomain	O
+with	O
+putative	O
+ligand	O
+-	O
+binding	O
+motifs	O
+.	O
+
+These	O
+well	O
+-	O
+characterized	O
+brain	O
+regions	O
+may	O
+provide	O
+a	O
+basis	O
+for	O
+future	O
+studies	O
+of	O
+RPTP	B-GENE
+-	I-GENE
+kappa	I-GENE
+function	O
+.	O
+
+Commonly	O
+used	O
+stressors	O
+are	O
+mental	O
+arithmetics	O
+,	O
+speech	O
+tasks	O
+,	O
+the	O
+Stroop	O
+test	O
+,	O
+videogame	O
+playing	O
+,	O
+films	O
+or	O
+videotapes	O
+and	O
+interviews	O
+.	O
+
+The	O
+control	O
+group	O
+included	O
+8	O
+afterbirth	O
+samples	O
+from	O
+physiological	O
+full	O
+-	O
+term	O
+pregnancies	O
+.	O
+
+However	O
+,	O
+we	O
+identified	O
+a	O
+gene	O
+between	O
+the	O
+MDV2	B-GENE
+UL54	I-GENE
+and	O
+UL55	B-GENE
+genes	I-GENE
+with	O
+homology	O
+to	O
+the	O
+first	B-GENE
+ORF	I-GENE
+(	I-GENE
+ORF	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+of	I-GENE
+equine	I-GENE
+herpesvirus	I-GENE
+type	I-GENE
+1	I-GENE
+and	O
+corresponding	O
+gene	O
+identified	O
+in	O
+pseudorabies	O
+virus	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+loss	O
+of	O
+MAD2	B-GENE
+staining	O
+in	O
+meiosis	O
+was	O
+not	O
+correlated	O
+with	O
+initial	O
+microtubule	O
+attachment	O
+but	O
+was	O
+correlated	O
+with	O
+a	O
+measure	O
+of	O
+tension	O
+:	O
+the	O
+distance	O
+between	O
+homologous	O
+or	O
+sister	O
+kinetochores	O
+(	O
+in	O
+meiosis	O
+I	O
+and	O
+II	O
+,	O
+respectively	O
+)	O
+.	O
+
+In	O
+epithelial	O
+cells	O
+,	O
+the	O
+PH	B-GENE
+domain	I-GENE
+of	O
+Akt	B-GENE
+/	O
+PKB	B-GENE
+localised	O
+to	O
+sites	O
+of	O
+cell	O
+-	O
+cell	O
+and	O
+cell	O
+-	O
+matrix	O
+contact	O
+,	O
+distinct	O
+from	O
+focal	O
+contacts	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+serum	O
+.	O
+
+The	O
+5	O
+'	O
+untranslated	O
+and	O
+coding	O
+regions	O
+are	O
+contained	O
+within	O
+12	O
+exons	O
+,	O
+with	O
+the	O
+translation	O
+start	O
+site	O
+located	O
+within	O
+the	O
+first	O
+exon	O
+.	O
+
+The	O
+motility	O
+of	O
+sperm	O
+,	O
+except	O
+for	O
+those	O
+adjacent	O
+to	O
+both	O
+electrodes	O
+,	O
+did	O
+not	O
+change	O
+after	O
+stimulation	O
+for	O
+60s	O
+,	O
+despite	O
+a	O
+high	O
+electrical	O
+energy	O
+.	O
+
+Induction	O
+of	O
+the	O
+CINC	B-GENE
+promoter	I-GENE
+by	O
+IL	B-GENE
+-	I-GENE
+17	I-GENE
+in	O
+IEC	O
+-	O
+6	O
+cells	O
+was	O
+TNF	B-GENE
+receptor	I-GENE
+-	I-GENE
+associated	I-GENE
+factor	I-GENE
+-	I-GENE
+6	I-GENE
+(	O
+TRAF6	B-GENE
+)	O
+,	O
+but	O
+not	O
+TRAF2	B-GENE
+,	O
+dependent	O
+.	O
+
+SCFFWD1	B-GENE
+may	O
+be	O
+critical	O
+for	O
+tumor	O
+development	O
+and	O
+suppression	O
+through	O
+regulation	O
+of	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+protein	I-GENE
+stability	O
+.	O
+
+A	O
+Bub2p	B-GENE
+-	O
+dependent	O
+spindle	O
+checkpoint	O
+pathway	O
+regulates	O
+the	O
+Dbf2p	B-GENE
+kinase	I-GENE
+in	I-GENE
+budding	I-GENE
+yeast	I-GENE
+.	O
+
+We	O
+analyzed	O
+the	O
+modular	O
+organization	O
+of	O
+DNA	B-GENE
+polymerase	I-GENE
+beta	I-GENE
+and	O
+found	O
+that	O
+residues	O
+making	O
+contact	O
+with	O
+DNA	O
+phosphates	O
+were	O
+localized	O
+to	O
+five	O
+modules	O
+.	O
+
+RESULTS	O
+:	O
+Cholinergic	O
+nerves	O
+are	O
+mainly	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+enteric	O
+nerve	O
+responses	O
+to	O
+EFS	O
+in	O
+the	O
+normal	O
+IAS	O
+.	O
+
+We	O
+show	O
+that	O
+other	O
+cdc33	B-GENE
+mutants	I-GENE
+also	O
+arrest	O
+in	O
+G1	O
+.	O
+
+A	O
+cdc33	B-GENE
+-	I-GENE
+1	I-GENE
+strain	O
+expressing	O
+either	O
+stable	O
+Cln3p	B-GENE
+(	O
+Cln3	B-GENE
+-	I-GENE
+1p	I-GENE
+)	O
+or	O
+a	O
+hybrid	O
+UBI4	B-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+CLN3	I-GENE
+mRNA	O
+,	O
+whose	O
+translation	O
+displays	O
+decreased	O
+dependence	O
+on	O
+eIF4E	B-GENE
+,	O
+arrested	O
+randomly	O
+in	O
+the	O
+cell	O
+cycle	O
+.	O
+
+Regulatory	O
+motifs	O
+for	O
+gene	O
+expression	O
+such	O
+as	O
+nuclear	B-GENE
+-	I-GENE
+factor	I-GENE
+-	I-GENE
+kappaB	I-GENE
+-	I-GENE
+binding	I-GENE
+-	I-GENE
+site	I-GENE
+-	I-GENE
+like	I-GENE
+sequence	I-GENE
+(	O
+kappaB	B-GENE
+site	I-GENE
+)	O
+and	O
+nuclear	B-GENE
+-	I-GENE
+factor	I-GENE
+-	I-GENE
+interleukin	I-GENE
+-	I-GENE
+6	I-GENE
+-	I-GENE
+binding	I-GENE
+-	I-GENE
+site	I-GENE
+-	I-GENE
+like	I-GENE
+sequence	I-GENE
+(	O
+NF	B-GENE
+-	I-GENE
+IL	I-GENE
+-	I-GENE
+6	I-GENE
+site	I-GENE
+)	O
+were	O
+found	O
+in	O
+the	O
+5	O
+'	O
+-	O
+upstream	O
+regulatory	O
+region	O
+.	O
+
+Total	O
+serum	O
+calcium	O
+was	O
+7	O
+.	O
+8	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+mg	O
+/	O
+dl	O
+,	O
+whereas	O
+ionized	O
+calcium	O
+was	O
+5	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+mg	O
+/	O
+dl	O
+,	O
+phosphorus	O
+3	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+mg	O
+/	O
+dl	O
+,	O
+and	O
+alkaline	B-GENE
+phosphatase	I-GENE
+149	O
++	O
+/	O
+-	O
+48	O
+.	O
+6	O
+U	O
+/	O
+liter	O
+.	O
+
+Cranio	O
+-	O
+caudal	O
+differences	O
+in	O
+granulation	O
+tissue	O
+formation	O
+:	O
+an	O
+experimental	O
+study	O
+in	O
+the	O
+rat	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+showed	O
+that	O
+two	O
+adjacent	O
+SP1	B-GENE
+sites	I-GENE
+proximal	O
+to	O
+exon	O
+1	O
+were	O
+equally	O
+important	O
+in	O
+sustaining	O
+basal	O
+promoter	O
+activity	O
+.	O
+
+Breast	O
+-	O
+fed	O
+newborn	O
+infants	O
+synthesize	O
+n	O
+-	O
+6	O
+long	O
+-	O
+chain	O
+polyunsaturated	O
+fatty	O
+acids	O
+already	O
+during	O
+the	O
+first	O
+week	O
+of	O
+life	O
+,	O
+but	O
+the	O
+contribution	O
+of	O
+endogenous	O
+synthesis	O
+to	O
+the	O
+total	O
+plasma	O
+long	O
+-	O
+chain	O
+polyunsaturated	O
+pool	O
+is	O
+small	O
+.	O
+
+Ischemia	O
+and	O
+reperfusion	O
+markedly	O
+increased	O
+the	O
+release	O
+of	O
+6	O
+-	O
+keto	O
+-	O
+PGF1	O
+alpha	O
+and	O
+TXB2	O
+.	O
+
+Prostate	B-GENE
+-	I-GENE
+specific	I-GENE
+antigen	I-GENE
+(	O
+PSA	B-GENE
+)	O
+promoter	O
+-	O
+driven	O
+androgen	O
+-	O
+inducible	O
+expression	O
+of	O
+sodium	B-GENE
+iodide	I-GENE
+symporter	I-GENE
+in	O
+prostate	O
+cancer	O
+cell	O
+lines	O
+.	O
+
+It	O
+is	O
+clear	O
+that	O
+subclinical	O
+and	O
+silent	O
+CD	O
+exist	O
+in	O
+a	O
+large	O
+subgroup	O
+of	O
+the	O
+celiac	O
+population	O
+.	O
+
+Ras2p	B-GENE
+activates	O
+invasive	O
+growth	O
+using	O
+either	O
+of	O
+two	O
+downstream	O
+signaling	O
+pathways	O
+,	O
+the	O
+filamentation	O
+MAPK	B-GENE
+(	O
+Cdc42p	B-GENE
+/	O
+Ste20p	B-GENE
+/	O
+MAPK	B-GENE
+)	O
+cascade	O
+or	O
+the	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+Cyr1p	B-GENE
+/	O
+cAMP	O
+/	O
+PKA	B-GENE
+)	O
+pathway	O
+.	O
+
+Consistent	O
+with	O
+this	O
+prediction	O
+,	O
+transfections	O
+into	O
+the	O
+hematopoietic	O
+cell	O
+line	O
+Jurkat	O
+showed	O
+a	O
+9	O
+.	O
+0	O
+-	O
+and	O
+2	O
+.	O
+5	O
+-	O
+fold	O
+activation	O
+of	O
+the	O
+mim	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+by	O
+the	O
+p32	B-GENE
+and	O
+p30	B-GENE
+isoforms	I-GENE
+,	O
+respectively	O
+.	O
+
+Despite	O
+the	O
+reported	O
+detrimental	O
+effects	O
+on	O
+CNS	O
+development	O
+,	O
+a	O
+number	O
+of	O
+animal	O
+studies	O
+have	O
+shown	O
+that	O
+pretreatment	O
+with	O
+corticosteroids	O
+nevertheless	O
+protect	O
+the	O
+brain	O
+from	O
+hypoxia	O
+-	O
+ischemic	O
+injury	O
+;	O
+however	O
+,	O
+clinically	O
+such	O
+treatment	O
+is	O
+no	O
+longer	O
+favored	O
+.	O
+
+In	O
+one	O
+mechanism	O
+,	O
+a	O
+specialized	O
+ubiquitin	B-GENE
+-	O
+dependent	O
+proteolytic	O
+system	O
+(	O
+called	O
+the	O
+APC	O
+-	O
+dependent	O
+proteolysis	O
+machinery	O
+)	O
+degrades	O
+the	O
+mitotic	O
+(	O
+Clb	B-GENE
+)	O
+cyclin	B-GENE
+subunit	I-GENE
+.	O
+
+Predictors	O
+of	O
+success	O
+in	O
+pharmacy	O
+school	O
+:	O
+PCAT	O
+vs	O
+.	O
+other	O
+admission	O
+criteria	O
+.	O
+
+Canadian	O
+survey	O
+reveals	O
+widespread	O
+dissatisfaction	O
+among	O
+physicians	O
+.	O
+
+In	O
+a	O
+series	O
+of	O
+16	O
+full	O
+-	O
+scale	O
+fire	O
+tests	O
+,	O
+investigators	O
+at	O
+the	O
+IIT	O
+Research	O
+Institute	O
+have	O
+concluded	O
+that	O
+automatic	O
+door	O
+control	O
+in	O
+the	O
+room	O
+of	O
+fire	O
+origin	O
+can	O
+significantly	O
+reduce	O
+the	O
+spread	O
+of	O
+toxic	O
+smoke	O
+and	O
+gases	O
+.	O
+
+Reporting	O
+of	O
+adverse	O
+events	O
+occurring	O
+during	O
+clinical	O
+trials	O
+of	O
+investigational	O
+drugs	O
+is	O
+a	O
+complex	O
+and	O
+controversial	O
+issue	O
+.	O
+
+Medicare	O
+SNF	O
+benefits	O
+revised	O
+-	O
+-	O
+again	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+the	O
+current	O
+status	O
+of	O
+the	O
+understanding	O
+of	O
+the	O
+interaction	O
+mechanisms	O
+of	O
+ultrasound	O
+with	O
+biological	O
+media	O
+and	O
+the	O
+factors	O
+that	O
+govern	O
+different	O
+biological	O
+effects	O
+are	O
+surveyed	O
+.	O
+
+Members	O
+of	O
+the	O
+mitogen	B-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinase	I-GENE
+family	I-GENE
+,	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+,	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+-	I-GENE
+1	I-GENE
+/	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+NH2	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+,	O
+and	O
+p38	B-GENE
+,	O
+are	O
+central	O
+elements	O
+that	O
+transduce	O
+the	O
+signal	O
+generated	O
+by	O
+growth	O
+factors	O
+,	O
+cytokines	O
+,	O
+and	O
+stressing	O
+agents	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+have	O
+investigated	O
+the	O
+functional	O
+role	O
+of	O
+the	O
+other	O
+MAP	B-GENE
+kinases	I-GENE
+in	O
+PDGF	B-GENE
+-	O
+mediated	O
+cellular	O
+responses	O
+.	O
+
+Analyses	O
+of	O
+tyrosine	O
+residue	O
+-	O
+mutated	O
+PDGF	B-GENE
+receptors	I-GENE
+show	O
+that	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+proteins	I-GENE
+including	O
+Src	B-GENE
+family	I-GENE
+kinases	I-GENE
+,	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+,	O
+the	O
+GTPase	B-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+of	O
+Ras	B-GENE
+,	O
+the	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+phosphatase	I-GENE
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+phospholipase	B-GENE
+C	I-GENE
+-	I-GENE
+gamma	I-GENE
+,	O
+and	O
+Crk	B-GENE
+do	O
+not	O
+play	O
+a	O
+major	O
+role	O
+in	O
+mediating	O
+the	O
+PDGF	B-GENE
+-	O
+induced	O
+activation	O
+of	O
+p38	B-GENE
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+calpeptin	B-GENE
+inhibits	O
+tyrosine	B-GENE
+phosphatases	I-GENE
+,	O
+enhancing	O
+tyrosine	O
+phosphorylation	O
+particularly	O
+of	O
+paxillin	B-GENE
+.	O
+
+Three	O
+-	O
+dimensional	O
+structural	O
+studies	O
+using	O
+electron	O
+cryomicroscopy	O
+showed	O
+that	O
+the	O
+binding	O
+of	O
+one	O
+Fab	B-GENE
+(	O
+8H2	O
+/	O
+G5	O
+)	O
+does	O
+not	O
+affect	O
+the	O
+conformation	O
+of	O
+the	O
+capsid	O
+,	O
+and	O
+the	O
+efficiency	O
+of	O
+mRNA	O
+production	O
+is	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+native	O
+subviral	O
+particle	O
+.	O
+
+Further	O
+,	O
+mutational	O
+analysis	O
+of	O
+NS5A	B-GENE
+assigned	O
+the	O
+SH3	B-GENE
+-	I-GENE
+binding	I-GENE
+region	I-GENE
+to	O
+a	O
+proline	O
+-	O
+rich	O
+motif	O
+that	O
+is	O
+highly	O
+conserved	O
+among	O
+HCV	O
+genotypes	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+findings	O
+show	O
+that	O
+16K	B-GENE
+hPRL	I-GENE
+inhibits	O
+the	O
+VEGF	B-GENE
+-	O
+induced	O
+Ras	B-GENE
+activation	O
+;	O
+this	O
+antagonism	O
+represents	O
+a	O
+novel	O
+and	O
+potentially	O
+important	O
+mechanism	O
+for	O
+the	O
+control	O
+of	O
+angiogenesis	O
+.	O
+
+Analysis	O
+of	O
+SRE	O
+oligonucleotide	O
+gel	O
+mobility	O
+shift	O
+assays	O
+with	O
+nuclear	O
+extracts	O
+from	O
+Sertoli	O
+cells	O
+demonstrated	O
+the	O
+presence	O
+of	O
+both	O
+the	O
+SRF	B-GENE
+and	O
+the	O
+ubiquitously	O
+expressed	O
+bHLH	O
+protein	O
+E12	B-GENE
+/	O
+E47	B-GENE
+.	O
+
+Baseline	O
+electrocorticography	O
+over	O
+the	O
+surface	O
+of	O
+the	O
+temporal	O
+lobe	O
+and	O
+depth	O
+electrode	O
+recordings	O
+in	O
+the	O
+amygdala	O
+and	O
+hippocampus	O
+were	O
+obtained	O
+,	O
+followed	O
+by	O
+10	O
+min	O
+of	O
+recording	O
+before	O
+and	O
+after	O
+the	O
+i	O
+.	O
+v	O
+.	O
+administration	O
+of	O
+both	O
+alfentanil	O
+50	O
+microg	O
+/	O
+kg	O
+and	O
+fentanyl	O
+10	O
+microg	O
+/	O
+kg	O
+.	O
+
+We	O
+suggest	O
+that	O
+FlgN	B-GENE
+and	O
+FliT	B-GENE
+are	O
+substrate	O
+-	O
+specific	O
+flagellar	O
+chaperones	O
+that	O
+prevent	O
+oligomerization	O
+of	O
+the	O
+HAPs	B-GENE
+by	O
+binding	O
+to	O
+their	O
+helical	O
+domains	O
+before	O
+export	O
+.	O
+
+Post	O
+and	O
+core	O
+fabrication	O
+for	O
+divergent	O
+canals	O
+with	O
+a	O
+cast	O
+post	O
+and	O
+core	O
+and	O
+a	O
+prefabricated	O
+dowel	O
+.	O
+
+Rep63A	B-GENE
+(	I-GENE
+513	I-GENE
+amino	I-GENE
+acids	I-GENE
+[	I-GENE
+aa	I-GENE
+]	I-GENE
+)	I-GENE
+,	O
+encoded	O
+by	O
+the	O
+largest	O
+ORF	O
+,	O
+displayed	O
+strong	O
+similarity	O
+(	O
+40	O
+%	O
+identity	O
+)	O
+to	O
+the	O
+replication	O
+proteins	O
+from	O
+plasmids	O
+pAMbeta1	O
+,	O
+pIP501	O
+,	O
+and	O
+pSM19035	O
+,	O
+indicating	O
+that	O
+the	O
+pAW63	O
+replicon	O
+belongs	O
+to	O
+the	O
+pAMbeta1	O
+family	O
+of	O
+gram	O
+-	O
+positive	O
+theta	O
+-	O
+replicating	O
+plasmids	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+cloning	O
+and	O
+characterization	O
+of	O
+Xenopus	B-GENE
+Pax	I-GENE
+-	I-GENE
+5	I-GENE
+and	O
+Pax	B-GENE
+-	I-GENE
+8	I-GENE
+,	O
+two	O
+orthologues	O
+of	O
+the	O
+Pax	B-GENE
+-	I-GENE
+2	I-GENE
+/	I-GENE
+5	I-GENE
+/	I-GENE
+8	I-GENE
+gene	I-GENE
+family	I-GENE
+.	O
+
+Km	O
+values	O
+for	O
+ammonium	O
+,	O
+2	O
+-	O
+oxoglutarate	O
+,	O
+NADH	O
+,	O
+glutamate	O
+and	O
+NAD	O
++	O
+were	O
+6	O
+.	O
+5	O
+,	O
+3	O
+.	O
+5	O
+,	O
+0	O
+.	O
+06	O
+,	O
+37	O
+.	O
+1	O
+and	O
+0	O
+.	O
+046	O
+mM	O
+,	O
+respectively	O
+.	O
+
+Interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+may	O
+exacerbate	O
+cryoblobulinemia	O
+-	O
+related	O
+ischemic	O
+manifestations	O
+:	O
+an	O
+adverse	O
+effect	O
+potentially	O
+related	O
+to	O
+its	O
+anti	O
+-	O
+angiogenic	O
+activity	O
+.	O
+
+Interferon	B-GENE
+-	I-GENE
+alpha	I-GENE
+may	O
+exacerbate	O
+cryoblobulinemia	O
+-	O
+related	O
+ischemic	O
+manifestations	O
+:	O
+an	O
+adverse	O
+effect	O
+potentially	O
+related	O
+to	O
+its	O
+anti	O
+-	O
+angiogenic	O
+activity	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+demonstrate	O
+that	O
+the	O
+production	O
+of	O
+active	B-GENE
+recombinant	I-GENE
+telomerase	I-GENE
+requires	O
+a	O
+factor	O
+in	O
+rabbit	O
+reticulocyte	O
+lysate	O
+that	O
+promotes	O
+ribonucleoprotein	O
+assembly	O
+.	O
+
+Homozygous	O
+mutation	O
+in	O
+two	O
+children	O
+led	O
+to	O
+amputation	O
+of	O
+legs	O
+due	O
+to	O
+purpura	O
+fulminans	O
+.	O
+
+According	O
+to	O
+pilot	O
+experiments	O
+which	O
+considered	O
+various	O
+durations	O
+of	O
+global	O
+no	O
+-	O
+flow	O
+ischemia	O
+ranging	O
+from	O
+10	O
+to	O
+20	O
+minutes	O
+,	O
+two	O
+durations	O
+were	O
+chosen	O
+for	O
+the	O
+present	O
+study	O
+:	O
+20	O
+minutes	O
+(	O
+group	O
+20	O
+)	O
+in	O
+which	O
+ventricular	O
+fibrillation	O
+(	O
+VF	O
+)	O
+was	O
+the	O
+predominant	O
+form	O
+of	O
+arrhythmias	O
+,	O
+and	O
+18	O
+minutes	O
+(	O
+group	O
+18	O
+)	O
+in	O
+which	O
+the	O
+prevalence	O
+of	O
+VF	O
+was	O
+markedly	O
+lower	O
+despite	O
+the	O
+small	O
+difference	O
+in	O
+the	O
+duration	O
+of	O
+ischemia	O
+.	O
+
+An	O
+end	O
+-	O
+to	O
+-	O
+end	O
+pancreaticojejunostomy	O
+using	O
+a	O
+mechanical	O
+purse	O
+-	O
+string	O
+device	O
+.	O
+
+Blood	O
+samples	O
+were	O
+obtained	O
+daily	O
+during	O
+this	O
+supplementation	O
+period	O
+and	O
+5	O
+d	O
+thereafter	O
+(	O
+d	O
+11	O
+to	O
+15	O
+)	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+mitochondrial	O
+presequences	O
+interact	O
+with	O
+the	O
+mt	B-GENE
+-	I-GENE
+hsp70	I-GENE
+during	O
+or	O
+after	O
+mitochondrial	O
+protein	O
+import	O
+.	O
+
+The	O
+3	O
+'	O
+terminus	O
+of	O
+the	O
+genome	O
+can	O
+be	O
+folded	O
+into	O
+a	O
+tRNA	O
+-	O
+like	O
+secondary	O
+structure	O
+that	O
+has	O
+a	O
+valine	O
+anticodon	O
+;	O
+the	O
+tRNA	O
+-	O
+like	O
+structure	O
+lacks	O
+a	O
+pseudoknot	O
+in	O
+the	O
+aminoacyl	O
+stem	O
+,	O
+a	O
+feature	O
+common	O
+to	O
+both	O
+genera	O
+of	O
+tetraviruses	O
+.	O
+
+Only	O
+one	O
+gene	O
+,	O
+fibronectin	B-GENE
+(	O
+FN	B-GENE
+)	O
+,	O
+was	O
+highly	O
+overexpressed	O
+(	O
+>	O
+60	O
+-	O
+fold	O
+)	O
+in	O
+LNCaP	O
+-	O
+r	O
+cells	O
+,	O
+consistent	O
+with	O
+previously	O
+reported	O
+overexpression	O
+of	O
+FN	B-GENE
+in	O
+prostate	O
+cancer	O
+.	O
+
+We	O
+also	O
+observed	O
+that	O
+cell	O
+surface	O
+CD4	B-GENE
+(	O
+-	O
+)	O
+CD8	B-GENE
+(	O
+-	O
+)	O
+CD3	B-GENE
+(	O
+-	O
+)	O
+cells	O
+with	O
+rearranged	B-GENE
+TCR	I-GENE
+genes	I-GENE
+developed	O
+from	O
+Id3	B-GENE
+-	O
+transduced	O
+but	O
+not	O
+from	O
+control	O
+-	O
+transduced	O
+pre	O
+-	O
+T	O
+cells	O
+in	O
+an	O
+FTOC	O
+.	O
+
+As	O
+determined	O
+in	O
+a	O
+modified	O
+yeast	O
+two	O
+-	O
+hybrid	O
+system	O
+,	O
+mIRS3	B-GENE
+bound	O
+strongly	O
+to	O
+the	O
+p85	B-GENE
+subunit	I-GENE
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+.	O
+
+Insulin	B-GENE
+stimulation	O
+promoted	O
+the	O
+association	O
+of	O
+mIRS3	B-GENE
+with	O
+p85	B-GENE
+,	O
+SHP2	B-GENE
+,	O
+Nck	B-GENE
+,	O
+and	O
+Shc	B-GENE
+.	O
+
+The	O
+mRNA	O
+expression	O
+of	O
+RFX1	B-GENE
+,	O
+RFX2	B-GENE
+,	O
+and	O
+RFX3	B-GENE
+was	O
+detected	O
+ubiquitously	O
+,	O
+but	O
+in	O
+transient	O
+-	O
+transfection	O
+assays	O
+,	O
+multimerized	B-GENE
+RFX	I-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+front	O
+of	O
+a	O
+basal	O
+promoter	O
+efficiently	O
+functioned	O
+in	O
+a	O
+tissue	O
+-	O
+and	O
+lineage	O
+-	O
+specific	O
+manner	O
+.	O
+
+In	O
+the	O
+case	O
+of	O
+the	O
+unspliceable	O
+intron	O
+,	O
+repression	O
+of	O
+luciferase	B-GENE
+expression	O
+likely	O
+involved	O
+two	O
+AUF1	B-GENE
+-	I-GENE
+binding	I-GENE
+sequences	I-GENE
+,	O
+since	O
+luciferase	B-GENE
+expression	O
+was	O
+increased	O
+by	O
+deletion	O
+of	O
+these	O
+sites	O
+.	O
+
+Thus	O
+,	O
+VDR	B-GENE
+acts	O
+selectively	O
+on	O
+the	O
+two	O
+components	O
+required	O
+for	O
+activation	O
+of	O
+this	O
+promoter	O
+/	O
+enhancer	O
+:	O
+it	O
+competes	O
+with	O
+NFAT1	B-GENE
+for	O
+binding	O
+to	O
+the	O
+composite	O
+site	O
+,	O
+positioning	O
+itself	O
+adjacent	O
+to	O
+Jun	B-GENE
+-	O
+Fos	B-GENE
+on	O
+the	O
+DNA	O
+.	O
+
+Two	O
+evolutionarily	O
+conserved	O
+kinases	O
+,	O
+the	O
+cyclin	B-GENE
+B	I-GENE
+(	O
+Clb	B-GENE
+)	O
+/	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+(	O
+Cdk	B-GENE
+/	O
+Cdc28p	B-GENE
+)	O
+and	O
+Cdc7p	B-GENE
+along	O
+with	O
+its	O
+interacting	O
+factor	O
+Dbf4p	B-GENE
+,	O
+are	O
+required	O
+late	O
+in	O
+G1	O
+to	O
+initiate	O
+DNA	O
+replication	O
+.	O
+
+The	O
+RanQ69L	B-GENE
+preincubation	O
+leads	O
+to	O
+accumulation	O
+of	O
+CRM1	B-GENE
+at	O
+the	O
+cytoplasmic	O
+periphery	O
+of	O
+the	O
+nuclear	O
+pore	O
+complex	O
+(	O
+NPC	O
+)	O
+in	O
+association	O
+with	O
+the	O
+p62	B-GENE
+complex	I-GENE
+and	O
+Can	B-GENE
+/	O
+Nup214	B-GENE
+.	O
+
+All	O
+of	O
+the	O
+elements	O
+exhibited	O
+a	O
+uniform	O
+structure	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+deduced	O
+amino	O
+acid	O
+sequence	O
+of	O
+a	O
+second	O
+family	O
+(	O
+ART5	B-GENE
+)	O
+of	O
+transferases	O
+,	O
+cloned	O
+from	O
+murine	O
+lymphoma	O
+cells	O
+and	O
+expressed	O
+in	O
+high	O
+abundance	O
+in	O
+testis	O
+,	O
+displays	O
+a	O
+hydrophobic	O
+amino	O
+terminus	O
+,	O
+consistent	O
+with	O
+a	O
+signal	O
+sequence	O
+,	O
+but	O
+lacks	O
+a	O
+hydrophobic	O
+signal	O
+sequence	O
+at	O
+its	O
+carboxyl	O
+terminus	O
+,	O
+suggesting	O
+that	O
+the	O
+protein	O
+is	O
+destined	O
+for	O
+export	O
+.	O
+
+RESULTS	O
+:	O
+Each	O
+year	O
+,	O
+on	O
+average	O
+39	O
+%	O
+of	O
+cases	O
+seen	O
+in	O
+Sardinia	O
+are	O
+notified	O
+;	O
+646	O
+(	O
+40	O
+%	O
+)	O
+of	O
+the	O
+1591	O
+patients	O
+notified	O
+during	O
+the	O
+study	O
+period	O
+were	O
+never	O
+seen	O
+by	O
+regional	O
+medical	O
+centres	O
+.	O
+
+This	O
+dimer	O
+interface	O
+is	O
+likely	O
+important	O
+for	O
+increasing	O
+the	O
+DNA	O
+-	O
+binding	O
+specificity	O
+and	O
+affinity	O
+of	O
+the	O
+trimeric	O
+form	O
+of	O
+HSF	B-GENE
+,	O
+as	O
+well	O
+as	O
+for	O
+increasing	O
+cooperativity	O
+between	O
+adjacent	O
+trimers	O
+.	O
+
+Additionally	O
+,	O
+deletion	O
+analysis	O
+of	O
+the	O
+UCP2	B-GENE
+promoter	O
+-	O
+PLAP	B-GENE
+constructs	O
+indicated	O
+that	O
+the	O
+minimal	O
+region	O
+exhibiting	O
+the	O
+promoter	O
+activity	O
+was	O
+located	O
+between	O
+nt	O
+-	O
+33	O
+and	O
++	O
+100	O
+,	O
+and	O
+that	O
+a	O
+strong	O
+enhancer	O
+was	O
+present	O
+within	O
+601	O
+bp	O
+of	O
+the	O
+5	O
+'	O
+-	O
+promoter	O
+region	O
+.	O
+
+The	O
+hTERT	B-GENE
+gene	I-GENE
+encompasses	O
+more	O
+than	O
+37kb	O
+and	O
+consists	O
+of	O
+16	O
+exons	O
+.	O
+
+Both	O
+betaAPP	B-GENE
+mRNA	I-GENE
+and	O
+Abeta	B-GENE
+levels	O
+are	O
+increased	O
+in	O
+trisomy	O
+21	O
+.	O
+
+In	O
+reperfusion	O
+B	O
+,	O
+only	O
+the	O
+diabetic	O
+group	O
+demonstrated	O
+a	O
+significant	O
+increase	O
+in	O
+IL	B-GENE
+-	I-GENE
+8	I-GENE
+concentrations	O
+at	O
+1	O
+and	O
+15	O
+min	O
+compared	O
+to	O
+nondiabetics	O
+.	O
+
+This	O
+repression	O
+was	O
+reversed	O
+agonists	O
+of	O
+either	O
+receptor	O
+demonstrating	O
+a	O
+functional	O
+interaction	O
+between	O
+NCoR	B-GENE
+and	O
+PPARalpha	B-GENE
+.	O
+RXRalpha	B-GENE
+heterodimeric	O
+complexes	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Spc42p	B-GENE
+also	O
+was	O
+identified	O
+as	O
+a	O
+component	O
+of	O
+a	O
+cytoplasmic	O
+SPB	O
+subcomplex	O
+containing	O
+Spc94p	B-GENE
+/	O
+Nud1p	B-GENE
+,	O
+Cnm67p	B-GENE
+,	O
+and	O
+Spc42p	B-GENE
+.	O
+
+The	O
+average	O
+coefficients	O
+of	O
+correlation	O
+were	O
+0	O
+.	O
+9998	O
+and	O
+0	O
+.	O
+9993	O
+for	O
+the	O
+QMF	O
+and	O
+the	O
+QIT	O
+system	O
+,	O
+respectively	O
+.	O
+
+The	O
+5	O
+-	O
+year	O
+OS	O
+for	O
+stage	O
+IIIB	O
+was	O
+30	O
+.	O
+9	O
+%	O
+,	O
+compared	O
+to	O
+7	O
+.	O
+8	O
+%	O
+for	O
+stage	O
+IV	O
+.	O
+
+Furthermore	O
+,	O
+heparin	B-GENE
+lyase	I-GENE
+treatment	O
+of	O
+extracts	O
+of	O
+cells	O
+expressing	O
+recombinant	B-GENE
+YD	I-GENE
+-	I-GENE
+repeat	I-GENE
+protein	I-GENE
+releases	O
+this	O
+protein	O
+from	O
+high	O
+molecular	O
+mass	O
+aggregates	O
+.	O
+
+CDK4	B-GENE
+kinase	I-GENE
+activities	O
+were	O
+unaffected	O
+,	O
+as	O
+were	O
+the	O
+levels	O
+of	O
+the	O
+CDK	B-GENE
+inhibitor	O
+p21Cip1	B-GENE
+present	O
+in	O
+cyclin	B-GENE
+E	I-GENE
+immunocomplexes	I-GENE
+.	O
+
+The	O
+recombinant	O
+purified	O
+protein	O
+expressed	O
+in	O
+the	O
+baculovirus	O
+system	O
+had	O
+an	O
+approximate	O
+molecular	O
+size	O
+20	O
+kDa	O
+with	O
+amino	O
+-	O
+terminal	O
+sequence	O
+of	O
+AVQGP	O
+.	O
+
+Induction	O
+of	O
+the	O
+urokinase	B-GENE
+promoter	I-GENE
+by	O
+HGF	B-GENE
+/	O
+SF	B-GENE
+via	O
+the	O
+Met	B-GENE
+receptor	I-GENE
+was	O
+blocked	O
+by	O
+co	O
+-	O
+expression	O
+of	O
+a	O
+dominant	O
+-	O
+negative	O
+Grb2	B-GENE
+and	O
+Sos1	B-GENE
+expression	O
+construct	O
+.	O
+
+Serine	O
+phosphorylation	O
+of	O
+STAT3	B-GENE
+was	O
+only	O
+apparent	O
+after	O
+somatostatin	B-GENE
+treatment	O
+and	O
+was	O
+abolished	O
+by	O
+pertussis	B-GENE
+toxin	I-GENE
+or	O
+PD	O
+98059	O
+,	O
+together	O
+with	O
+the	O
+associated	O
+increases	O
+in	O
+proliferation	O
+.	O
+
+Nevertheless	O
+,	O
+we	O
+demonstrate	O
+that	O
+the	O
+entire	O
+three	O
+-	O
+component	O
+yeast	O
+capping	O
+apparatus	O
+,	O
+consisting	O
+of	O
+RNA	B-GENE
+5	I-GENE
+'	I-GENE
+-	I-GENE
+triphosphatase	I-GENE
+(	O
+Cet1p	B-GENE
+)	O
+,	O
+RNA	B-GENE
+guanylyltransferase	I-GENE
+(	O
+Ceg1p	B-GENE
+)	O
+,	O
+and	O
+Abd1p	B-GENE
+could	O
+be	O
+replaced	O
+in	O
+vivo	O
+by	O
+the	O
+two	O
+-	O
+component	O
+mammalian	O
+apparatus	O
+consisting	O
+of	O
+a	O
+bifunctional	O
+triphosphatase	B-GENE
+-	I-GENE
+guanylyltransferase	I-GENE
+Mce1p	I-GENE
+and	O
+the	O
+methyltransferase	B-GENE
+Hcm1	I-GENE
+(	I-GENE
+121	I-GENE
+-	I-GENE
+476	I-GENE
+)	I-GENE
+p	I-GENE
+.	O
+
+The	O
+IC50	O
+values	O
+for	O
+rat	O
+and	O
+dog	O
+urinary	O
+bladder	O
+were	O
+3	O
+.	O
+9	O
+x	O
+10	O
+(	O
+-	O
+6	O
+)	O
+M	O
+and	O
+3	O
+.	O
+8	O
+x	O
+10	O
+(	O
+-	O
+6	O
+)	O
+M	O
+,	O
+respectively	O
+.	O
+
+Although	O
+it	O
+has	O
+two	O
+potential	O
+binding	O
+sites	O
+,	O
+the	O
+purified	O
+MerR	B-GENE
+homodimer	I-GENE
+binds	O
+only	O
+one	O
+Hg	O
+(	O
+II	O
+)	O
+ion	O
+,	O
+employing	O
+Cys82	O
+from	O
+one	O
+monomer	O
+and	O
+Cys117	O
+and	O
+Cys126	O
+from	O
+the	O
+other	O
+.	O
+
+The	O
+influence	O
+of	O
+Epstein	O
+-	O
+Barr	O
+virus	O
+seropositivity	O
+on	O
+the	O
+efficacy	O
+of	O
+intravenous	O
+immune	B-GENE
+globulin	I-GENE
+in	O
+children	O
+with	O
+immune	O
+thrombocytopenic	O
+purpura	O
+.	O
+
+The	O
+results	O
+of	O
+the	O
+lab	O
+and	O
+field	O
+tests	O
+yielded	O
+high	O
+levels	O
+of	O
+infestation	O
+in	O
+larvae	O
+with	O
+values	O
+ranging	O
+from	O
+90	O
+to	O
+100	O
+%	O
+and	O
+from	O
+85	O
+to	O
+95	O
+%	O
+,	O
+respectively	O
+.	O
+
+Amisulpride	O
+400	O
+mg	O
+had	O
+several	O
+adverse	O
+effects	O
+on	O
+psychomotor	O
+and	O
+,	O
+although	O
+less	O
+severe	O
+,	O
+on	O
+cognitive	O
+performance	O
+on	O
+the	O
+fifth	O
+day	O
+only	O
+.	O
+
+MutY	B-GENE
+is	O
+an	O
+adenine	B-GENE
+-	I-GENE
+DNA	I-GENE
+glycosylase	I-GENE
+with	O
+specificity	O
+for	O
+mismatches	O
+involving	O
+8	O
+-	O
+oxoguanine	O
+(	O
+oG	O
+.	O
+A	O
+)	O
+or	O
+guanine	O
+(	O
+G	O
+.	O
+A	O
+)	O
+.	O
+
+The	O
+kinetics	O
+of	O
+kinase	O
+activity	O
+within	O
+these	O
+complexes	O
+compared	O
+to	O
+CheA	B-GENE
+alone	O
+indicate	O
+approximately	O
+a	O
+50	O
+%	O
+decrease	O
+in	O
+the	O
+KM	O
+for	O
+ATP	O
+and	O
+a	O
+100	O
+-	O
+fold	O
+increase	O
+in	O
+the	O
+Vmax	O
+.	O
+
+Latexin	B-GENE
+,	O
+a	O
+carboxypeptidase	B-GENE
+A	I-GENE
+inhibitor	O
+,	O
+is	O
+expressed	O
+in	O
+a	O
+cell	O
+type	O
+-	O
+specific	O
+manner	O
+in	O
+both	O
+central	O
+and	O
+peripheral	O
+nervous	O
+systems	O
+in	O
+the	O
+rat	O
+.	O
+
+Regression	O
+analyses	O
+identified	O
+7	O
+risk	O
+and	O
+7	O
+protective	O
+factors	O
+with	O
+minimal	O
+overlap	O
+.	O
+
+During	O
+1985	O
+,	O
+1990	O
+,	O
+and	O
+1995	O
+,	O
+respectively	O
+,	O
+11	O
+.	O
+7	O
+,	O
+11	O
+.	O
+3	O
+,	O
+and	O
+11	O
+.	O
+4	O
+infants	O
+per	O
+100	O
+,	O
+000	O
+live	O
+births	O
+had	O
+a	O
+diagnosis	O
+of	O
+HSV	O
+(	O
+P	O
+=	O
+.	O
+98	O
+)	O
+.	O
+
+Subsets	O
+of	O
+patients	O
+were	O
+performed	O
+according	O
+to	O
+the	O
+severity	O
+of	O
+trauma	O
+(	O
+ISS	O
+<	O
+9	O
+;	O
+9	O
+-	O
+17	O
+;	O
+18	O
+-	O
+31	O
+;	O
+>	O
+32	O
+)	O
+,	O
+based	O
+on	O
+the	O
+different	O
+injury	O
+pattern	O
+,	O
+and	O
+survivors	O
+versus	O
+nonsurvivors	O
+as	O
+well	O
+.	O
+
+The	O
+median	O
+age	O
+was	O
+33	O
+years	O
+(	O
+range	O
+17	O
+-	O
+56	O
+years	O
+)	O
+.	O
+
+Developmental	O
+follow	O
+-	O
+up	O
+at	O
+age	O
+2	O
+years	O
+was	O
+performed	O
+.	O
+
+In	O
+the	O
+whole	O
+group	O
+of	O
+infected	O
+children	O
+,	O
+an	O
+age	O
+-	O
+specific	O
+z	O
+score	O
+<	O
+-	O
+2	O
+for	O
+weight	O
+and	O
+for	O
+FFM	O
+was	O
+significantly	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+of	O
+death	O
+[	O
+relative	O
+risk	O
+(	O
+95	O
+%	O
+CI	O
+)	O
+=	O
+11	O
+.	O
+4	O
+(	O
+3	O
+.	O
+1	O
+,	O
+41	O
+.	O
+0	O
+)	O
+and	O
+5	O
+.	O
+1	O
+(	O
+1	O
+.	O
+5	O
+,	O
+18	O
+.	O
+2	O
+)	O
+,	O
+respectively	O
+]	O
+;	O
+when	O
+only	O
+children	O
+with	O
+more	O
+severe	O
+disease	O
+were	O
+considered	O
+,	O
+only	O
+z	O
+score	O
+for	O
+weight	O
+was	O
+significantly	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+[	O
+4	O
+.	O
+6	O
+(	O
+1	O
+.	O
+4	O
+,	O
+14	O
+.	O
+9	O
+)	O
+]	O
+.	O
+
+In	O
+addition	O
+,	O
+these	O
+cells	O
+contained	O
+one	O
+,	O
+two	O
+,	O
+or	O
+multiple	O
+nuclei	O
+indicative	O
+of	O
+a	O
+G2	O
+/	O
+M	O
+delay	O
+in	O
+nuclear	O
+division	O
+and	O
+also	O
+a	O
+defect	O
+in	O
+cytokinesis	O
+and	O
+/	O
+or	O
+cell	O
+separation	O
+.	O
+
+DAF16	B-GENE
+is	O
+known	O
+to	O
+be	O
+a	O
+component	O
+of	O
+a	O
+signaling	O
+pathway	O
+that	O
+has	O
+been	O
+partially	O
+dissected	O
+genetically	O
+and	O
+includes	O
+homologues	O
+of	O
+the	O
+insulin	B-GENE
+/	O
+IGF	B-GENE
+-	I-GENE
+1	I-GENE
+receptor	I-GENE
+,	O
+PtdIns	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+and	O
+PKB	B-GENE
+.	O
+
+However	O
+,	O
+neu	B-GENE
+differentiation	O
+factor	O
+-	O
+induced	O
+heterodimers	O
+of	O
+ErbB2	B-GENE
+and	O
+ErbB4	B-GENE
+activated	O
+Stat5	B-GENE
+.	O
+
+Although	O
+linker	O
+regions	O
+in	O
+transcription	O
+factors	O
+are	O
+known	O
+to	O
+modulate	O
+DNA	O
+binding	O
+specificity	O
+,	O
+our	O
+studies	O
+suggest	O
+that	O
+the	O
+human	B-GENE
+HSF1	I-GENE
+linker	O
+plays	O
+no	O
+role	O
+in	O
+determining	O
+HSF1	B-GENE
+binding	O
+preferences	O
+in	O
+vivo	O
+but	O
+is	O
+a	O
+critical	O
+determinant	O
+in	O
+regulating	O
+the	O
+HSF1	B-GENE
+monomer	I-GENE
+-	I-GENE
+trimer	I-GENE
+equilibrium	O
+.	O
+
+Modulation	O
+of	O
+human	B-GENE
+heat	I-GENE
+shock	I-GENE
+factor	I-GENE
+trimerization	O
+by	O
+the	O
+linker	O
+domain	O
+.	O
+
+Both	O
+functional	O
+analyses	O
+in	O
+undifferentiated	O
+and	O
+differentiated	O
+F9	O
+cells	O
+and	O
+characterization	O
+of	O
+DNA	O
+-	O
+protein	O
+complexes	O
+in	O
+vitro	O
+have	O
+identified	O
+the	O
+sequence	O
+motifs	O
+GTGACT	O
+(	O
+C	O
+)	O
+,	O
+ATTGT	O
+,	O
+and	O
+GATA	O
+as	O
+the	O
+key	O
+transcription	O
+factor	O
+binding	O
+sites	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+the	O
+phenotype	O
+of	O
+XLP	O
+may	O
+result	O
+from	O
+perturbed	O
+signaling	O
+not	O
+only	O
+through	O
+SLAM	B-GENE
+,	O
+but	O
+also	O
+other	O
+cell	O
+surface	O
+molecules	O
+that	O
+utilize	O
+SAP	B-GENE
+as	O
+a	O
+signaling	O
+adaptor	O
+protein	O
+.	O
+
+We	O
+also	O
+localized	O
+the	O
+Fra	B-GENE
+-	I-GENE
+2	I-GENE
+phosphorylation	I-GENE
+sites	I-GENE
+by	O
+MAPK	B-GENE
+to	O
+three	O
+threonine	O
+and	O
+three	O
+serine	O
+residues	O
+in	O
+the	O
+COOH	O
+-	O
+terminal	O
+region	O
+by	O
+means	O
+of	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+and	O
+showed	O
+that	O
+the	O
+threonine	O
+residues	O
+were	O
+more	O
+susceptible	O
+to	O
+MAPK	B-GENE
+.	O
+
+Nevertheless	O
+,	O
+they	O
+are	O
+functionally	O
+distinct	O
+in	O
+that	O
+FcalphaRI	B-GENE
+binds	O
+human	B-GENE
+IgA	I-GENE
+(	O
+hIgA	B-GENE
+)	O
+but	O
+not	O
+bovine	B-GENE
+IgG2	I-GENE
+(	O
+bIgG2	B-GENE
+)	O
+,	O
+whereas	O
+bFcgamma2R	B-GENE
+binds	O
+bIgG2	B-GENE
+but	O
+not	O
+hIgA	B-GENE
+.	O
+
+Vac1p	B-GENE
+was	O
+found	O
+to	O
+bind	O
+the	O
+Sec1p	B-GENE
+homologue	I-GENE
+Vps45p	B-GENE
+.	O
+
+To	O
+identify	O
+these	O
+sites	O
+,	O
+Cdk2	B-GENE
+-	O
+phosphorylated	O
+MARCKS	B-GENE
+was	O
+digested	O
+with	O
+lysyl	B-GENE
+endoprotease	I-GENE
+and	O
+analysed	O
+by	O
+electrospray	O
+MS	O
+.	O
+
+The	O
+yeast	B-GENE
+LPD1	I-GENE
+gene	I-GENE
+encoding	O
+lipoamide	B-GENE
+dehydrogenase	I-GENE
+is	O
+subject	O
+to	O
+the	O
+general	O
+control	O
+of	O
+amino	O
+acid	O
+biosynthesis	O
+mediated	O
+by	O
+the	O
+GCN4	B-GENE
+transcription	I-GENE
+factor	I-GENE
+.	O
+
+However	O
+,	O
+the	O
+serum	B-GENE
+TNF	I-GENE
+-	I-GENE
+a	I-GENE
+concentration	O
+decreased	O
+significantly	O
+in	O
+patients	O
+receiving	O
+pentoxifylline	O
+(	O
+basal	O
+623	O
++	O
+/	O
+-	O
+366	O
+pg	O
+/	O
+ml	O
+;	O
+6th	O
+month	O
+562	O
++	O
+/	O
+-	O
+358	O
+pg	O
+/	O
+ml	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+but	O
+not	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+show	O
+that	O
+the	O
+expression	O
+of	O
+individual	O
+members	O
+of	O
+one	O
+subfamily	O
+of	O
+KRAB	B-GENE
+zinc	I-GENE
+finger	I-GENE
+genes	I-GENE
+is	O
+restricted	O
+to	O
+specific	O
+hematopoietic	O
+cell	O
+lineages	O
+.	O
+
+Employing	O
+fluorescence	O
+spectroscopy	O
+and	O
+circular	O
+dichroism	O
+,	O
+we	O
+showed	O
+that	O
+the	O
+binding	O
+of	O
+Ca2	O
++	O
+to	O
+ALG	B-GENE
+-	I-GENE
+2	I-GENE
+induced	O
+significant	O
+conformational	O
+changes	O
+in	O
+both	O
+the	O
+N	O
+-	O
+terminal	O
+and	O
+C	O
+-	O
+terminal	O
+domains	O
+of	O
+the	O
+protein	O
+.	O
+
+They	O
+also	O
+occur	O
+in	O
+similar	O
+locations	O
+in	O
+the	O
+promoters	O
+of	O
+several	O
+other	O
+ribosomal	B-GENE
+protein	I-GENE
+genes	I-GENE
+.	O
+
+RESULTS	O
+:	O
+Transpulmonary	O
+passage	O
+of	O
+contrast	O
+occurred	O
+in	O
+sufficient	O
+amounts	O
+to	O
+enhance	O
+the	O
+intensity	O
+of	O
+the	O
+Doppler	O
+signal	O
+significantly	O
+,	O
+but	O
+the	O
+duration	O
+of	O
+this	O
+effect	O
+was	O
+short	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+such	O
+lesions	O
+in	O
+two	O
+cases	O
+were	O
+evaluated	O
+by	O
+ultrasonography	O
+.	O
+
+These	O
+regions	O
+contain	O
+inverted	O
+E	O
+-	O
+box	O
+palindromic	O
+or	O
+direct	O
+repeat	O
+motifs	O
+and	O
+bind	O
+SREBP	B-GENE
+-	I-GENE
+1	I-GENE
+with	O
+different	O
+affinities	O
+.	O
+
+To	O
+address	O
+these	O
+questions	O
+,	O
+a	O
+recombinant	O
+FRAP	B-GENE
+/	O
+mTOR	B-GENE
+protein	O
+and	O
+a	O
+FRAP	B-GENE
+/	O
+mTOR	B-GENE
+immunoprecipitate	O
+were	O
+utilized	O
+in	O
+in	O
+vitro	O
+kinase	O
+assays	O
+to	O
+phosphorylate	O
+4E	B-GENE
+-	I-GENE
+BP1	I-GENE
+.	O
+
+The	O
+coexpression	O
+of	O
+full	O
+-	O
+length	O
+expression	O
+constructs	O
+for	O
+both	O
+DBP	B-GENE
+and	O
+hepatic	B-GENE
+leukemia	I-GENE
+factor	I-GENE
+resulted	O
+in	O
+a	O
+dramatic	O
+increase	O
+in	O
+activation	O
+mediated	O
+by	O
+the	O
+GAL4	B-GENE
+-	O
+DBP	B-GENE
+fusion	O
+proteins	O
+,	O
+suggesting	O
+the	O
+involvement	O
+of	O
+a	O
+regulated	O
+coactivator	O
+in	O
+this	O
+process	O
+.	O
+
+Cp	B-GENE
+is	O
+normally	O
+the	O
+main	O
+promoter	O
+for	O
+EBNA	B-GENE
+mRNA	I-GENE
+initiation	O
+,	O
+so	O
+it	O
+appears	O
+that	O
+EBNA3C	B-GENE
+contributes	O
+to	O
+a	O
+negative	O
+autoregulatory	O
+control	O
+loop	O
+.	O
+
+These	O
+indications	O
+of	O
+deregulated	O
+signalling	O
+in	O
+the	O
+absence	O
+of	O
+tyrosine	O
+118	O
+were	O
+substantiated	O
+by	O
+sustained	O
+activation	O
+of	O
+STAT3	B-GENE
+.	O
+
+With	O
+exon	O
+trapping	O
+,	O
+we	O
+could	O
+isolate	O
+five	O
+potential	O
+exons	O
+from	O
+the	O
+YAC	O
+946E12	O
+that	O
+spans	O
+the	O
+region	O
+,	O
+four	O
+of	O
+which	O
+could	O
+be	O
+placed	O
+in	O
+the	O
+contig	O
+in	O
+the	O
+vicinity	O
+of	O
+the	O
+breakpoints	O
+.	O
+
+Campomelic	O
+dysplasia	O
+translocation	O
+breakpoints	O
+are	O
+scattered	O
+over	O
+1	O
+Mb	O
+proximal	O
+to	O
+SOX9	B-GENE
+:	O
+evidence	O
+for	O
+an	O
+extended	O
+control	O
+region	O
+.	O
+
+The	O
+most	O
+common	O
+characteristics	O
+of	O
+VRE	O
+patients	O
+were	O
+recent	O
+prior	O
+vancomycin	O
+use	O
+,	O
+recent	O
+prior	O
+susceptible	O
+enterococcal	O
+infection	O
+,	O
+coinfection	O
+with	O
+other	O
+microbial	O
+pathogens	O
+,	O
+and	O
+concurrent	O
+fungal	O
+infection	O
+.	O
+
+A	O
+coiled	O
+-	O
+coil	O
+domain	O
+,	O
+conserved	O
+within	O
+each	O
+encoded	O
+protein	O
+,	O
+serves	O
+as	O
+a	O
+potential	O
+interaction	O
+motif	O
+for	O
+FLI	B-GENE
+LRR	I-GENE
+.	O
+
+Binding	O
+affinities	O
+of	O
+these	O
+recombinant	O
+phages	O
+as	O
+determined	O
+by	O
+the	O
+retention	O
+of	O
+these	O
+phages	O
+by	O
+a	O
+His	O
+-	O
+tag	O
+immobilized	O
+gp17	B-GENE
+column	O
+,	O
+and	O
+by	O
+co	O
+-	O
+immunoprecipitation	O
+with	O
+purified	O
+terminase	B-GENE
+supported	O
+the	O
+specific	O
+nature	O
+of	O
+the	O
+portal	B-GENE
+protein	I-GENE
+and	O
+terminase	B-GENE
+interaction	I-GENE
+sites	I-GENE
+.	O
+
+Although	O
+the	O
+terminase	B-GENE
+apparently	O
+interacts	O
+with	O
+this	O
+gp20	B-GENE
+portal	I-GENE
+peptide	I-GENE
+,	O
+polyclonal	O
+antibody	O
+against	O
+the	O
+portal	O
+peptide	O
+appears	O
+unable	O
+to	O
+access	O
+it	O
+in	O
+the	O
+native	O
+structure	O
+,	O
+suggesting	O
+intimate	O
+association	O
+of	O
+gp20	B-GENE
+and	O
+gp17	B-GENE
+possibly	O
+internalizes	O
+terminase	B-GENE
+regions	I-GENE
+within	O
+the	O
+portal	O
+in	O
+the	O
+packasome	O
+complex	O
+.	O
+
+cDNA	O
+and	O
+structural	O
+organization	O
+of	O
+the	O
+gene	B-GENE
+Pole1	I-GENE
+for	O
+the	O
+mouse	B-GENE
+DNA	I-GENE
+polymerase	I-GENE
+epsilon	I-GENE
+catalytic	I-GENE
+subunit	I-GENE
+.	O
+
+A	O
+liquid	O
+chromatographic	O
+method	O
+is	O
+described	O
+for	O
+analysis	O
+of	O
+beta	O
+-	O
+carotene	O
+in	O
+medical	O
+food	O
+.	O
+
+The	O
+FCMS	O
+conditions	O
+were	O
+as	O
+follows	O
+:	O
+2	O
+kW	O
+maximum	O
+electrical	O
+power	O
+consumption	O
+,	O
+800	O
+V	O
+maximum	O
+capacitor	O
+voltage	O
+,	O
+720	O
+microseconds	O
+pulsewidth	O
+(	O
+180	O
+microseconds	O
+rise	O
+time	O
+)	O
+,	O
+and	O
+5	O
+-	O
+30	O
+Hz	O
+frequency	O
+.	O
+
+Severe	O
+hemolysis	O
+resulted	O
+in	O
+statistically	O
+significant	O
+changes	O
+in	O
+the	O
+mean	O
+values	O
+of	O
+the	O
+above	O
+analytes	O
+in	O
+addition	O
+to	O
+the	O
+following	O
+increases	O
+:	O
+alanine	B-GENE
+aminotransferase	I-GENE
+,	O
+calcium	O
+,	O
+and	O
+serum	B-GENE
+globulins	I-GENE
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+albumin	B-GENE
+and	O
+total	O
+protein	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Optimal	O
+monitoring	O
+of	O
+ODA	O
+remains	O
+undefined	O
+.	O
+
+The	O
+exon	O
+:	O
+intron	O
+structure	O
+of	O
+chicken	B-GENE
+IL8	I-GENE
+corresponds	O
+almost	O
+exactly	O
+to	O
+that	O
+of	O
+human	B-GENE
+IL8	I-GENE
+and	O
+differs	O
+from	O
+those	O
+of	O
+other	O
+known	O
+mammalian	B-GENE
+CXC	I-GENE
+chemokine	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+Aa	B-GENE
+-	I-GENE
+Pri2	I-GENE
+gene	I-GENE
+,	O
+specifically	O
+expressed	O
+during	O
+basidiocarp	O
+differentiation	O
+of	O
+the	O
+mushroom	O
+Agrocybe	O
+aegerita	O
+,	O
+was	O
+cloned	O
+.	O
+
+The	O
+main	O
+causes	O
+of	O
+liver	O
+disease	O
+in	O
+the	O
+patients	O
+with	O
+HCC	O
+were	O
+hepatitis	O
+C	O
+virus	O
+(	O
+HCV	O
+)	O
+(	O
+77	O
+%	O
+)	O
+,	O
+alcohol	O
+abuse	O
+(	O
+73	O
+%	O
+)	O
+,	O
+and	O
+the	O
+combination	O
+of	O
+HCV	O
+and	O
+alcohol	O
+abuse	O
+(	O
+50	O
+%	O
+)	O
+.	O
+
+Three	O
+new	O
+aromatase	B-GENE
+inhibitors	O
+have	O
+recently	O
+completed	O
+phase	O
+III	O
+evaluation	O
+as	O
+treatment	O
+of	O
+metastatic	O
+breast	O
+cancer	O
+in	O
+post	O
+-	O
+menopausal	O
+women	O
+whose	O
+disease	O
+has	O
+progressed	O
+despite	O
+tamoxifen	O
+therapy	O
+:	O
+anastrozole	O
+(	O
+ARIMIDEX	O
+,	O
+Zeneca	O
+)	O
+,	O
+letrozole	O
+(	O
+FEMARA	O
+,	O
+Novartis	O
+)	O
+and	O
+vorozole	O
+(	O
+RIVIZOR	O
+,	O
+Janssen	O
+)	O
+.	O
+
+Of	O
+those	O
+injuries	O
+,	O
+143	O
+cases	O
+were	O
+snowboard	O
+related	O
+and	O
+158	O
+cases	O
+were	O
+ski	O
+related	O
+.	O
+
+The	O
+femoral	O
+artery	O
+/	O
+vein	O
+and	O
+the	O
+soleus	O
+and	O
+gastrocnemius	O
+muscles	O
+were	O
+examined	O
+in	O
+healthy	O
+human	O
+male	O
+volunteers	O
+.	O
+
+SRFDelta5	B-GENE
+acts	O
+as	O
+a	O
+naturally	O
+occurring	O
+dominant	O
+negative	O
+regulatory	O
+mutant	O
+that	O
+blocks	O
+SRF	B-GENE
+-	O
+dependent	O
+skeletal	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+,	O
+cardiac	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+,	O
+smooth	B-GENE
+alpha	I-GENE
+-	I-GENE
+actin	I-GENE
+,	O
+SM22alpha	B-GENE
+,	O
+and	O
+SRF	B-GENE
+promoter	O
+-	O
+luciferase	B-GENE
+reporter	O
+activities	O
+.	O
+
+In	O
+serum	O
+-	O
+free	O
+media	O
+,	O
+p50E4F	B-GENE
+accelerated	O
+E1A	B-GENE
+-	O
+induced	O
+apoptosis	O
+.	O
+
+Progression	O
+after	O
+first	O
+-	O
+line	O
+chemotherapy	O
+was	O
+associated	O
+with	O
+significantly	O
+worse	O
+survival	O
+for	O
+patients	O
+with	O
+metastasis	O
+.	O
+
+Mutations	O
+within	O
+human	O
+UTR1	O
+modulate	O
+NRF	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+by	O
+interfering	O
+with	O
+mRNA	O
+translational	O
+efficiency	O
+in	O
+transfected	O
+cells	O
+and	O
+in	O
+an	O
+in	O
+vitro	O
+translation	O
+system	O
+.	O
+
+As	O
+is	O
+deduced	O
+from	O
+the	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+cDNA	O
+,	O
+CBS	B-GENE
+-	I-GENE
+1	I-GENE
+contains	O
+an	O
+open	O
+reading	O
+frame	O
+consisting	O
+of	O
+182	O
+amino	O
+acids	O
+,	O
+with	O
+a	O
+molecular	O
+weight	O
+of	O
+19	O
+.	O
+5kDa	O
+.	O
+
+Corticostriatal	O
+and	O
+corticosubthalamic	O
+input	O
+zones	O
+from	O
+the	O
+presupplementary	O
+motor	O
+area	O
+in	O
+the	O
+macaque	O
+monkey	O
+:	O
+comparison	O
+with	O
+the	O
+input	O
+zones	O
+from	O
+the	O
+supplementary	O
+motor	O
+area	O
+.	O
+
+Basic	B-GENE
+fibroblast	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+bFGF	B-GENE
+)	O
+has	O
+been	O
+shown	O
+to	O
+induce	O
+angiogenesis	O
+in	O
+various	O
+animal	O
+models	O
+,	O
+but	O
+the	O
+methods	O
+of	O
+administration	O
+used	O
+experimentally	O
+are	O
+not	O
+clinically	O
+feasible	O
+.	O
+
+Both	O
+filters	O
+equally	O
+contributed	O
+to	O
+elevation	O
+of	O
+iliac	O
+venous	O
+pressure	O
+(	O
+median	O
+,	O
+9	O
+.	O
+3	O
+and	O
+7	O
+.	O
+2	O
+mm	O
+Hg	O
+[	O
+n	O
+=	O
+9	O
+]	O
+with	O
+the	O
+spring	O
+filter	O
+and	O
+RF02	O
+filter	O
+,	O
+respectively	O
+)	O
+.	O
+
+12	O
+healthy	O
+women	O
+(	O
+age	O
+18	O
+-	O
+38	O
+years	O
+)	O
+were	O
+examined	O
+using	O
+the	O
+2	O
+-	O
+hour	O
+'	O
+s	O
+method	O
+of	O
+passive	O
+leg	O
+rising	O
+(	O
+PLR	O
+)	O
+in	O
+follicular	O
+(	O
+FP	O
+)	O
+and	O
+luteal	O
+(	O
+LP	O
+)	O
+phases	O
+of	O
+normal	O
+ovulatory	O
+cycle	O
+.	O
+
+Thus	O
+,	O
+sgRNA2	B-GENE
+has	O
+the	O
+3	O
+'	O
+TE	O
+in	O
+its	O
+5	O
+'	O
+UTR	O
+.	O
+
+These	O
+single	O
+mutational	O
+defects	O
+in	O
+the	O
+eRF1	B-GENE
+-	O
+eRF3	B-GENE
+interaction	O
+became	O
+evident	O
+when	O
+either	O
+truncated	O
+protein	O
+eRF3C	B-GENE
+or	O
+C	O
+-	O
+terminally	O
+altered	O
+eRF1	B-GENE
+proteins	O
+were	O
+used	O
+for	O
+the	O
+authentic	O
+protein	O
+,	O
+providing	O
+further	O
+support	O
+for	O
+the	O
+presence	O
+of	O
+a	O
+C	O
+-	O
+terminal	O
+interaction	O
+.	O
+
+Removal	O
+of	O
+each	O
+of	O
+three	O
+contiguous	O
+segments	O
+from	O
+the	O
+N	O
+-	O
+terminal	O
+half	O
+specifically	O
+inhibits	O
+the	O
+formation	O
+of	O
+5	B-GENE
+.	I-GENE
+8Ss	I-GENE
+rRNA	I-GENE
+,	O
+whereas	O
+deleting	O
+part	O
+of	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+protein	O
+only	O
+blocks	O
+the	O
+production	O
+of	O
+18S	B-GENE
+rRNA	I-GENE
+.	O
+
+Ras	B-GENE
+is	O
+not	O
+associated	O
+with	O
+the	O
+tegument	O
+.	O
+
+Green	O
+fluorescent	O
+protein	O
+-	O
+tagged	O
+UNC	B-GENE
+-	I-GENE
+49B	I-GENE
+and	O
+UNC	B-GENE
+-	I-GENE
+49C	I-GENE
+subunits	I-GENE
+are	O
+coexpressed	O
+in	O
+muscle	O
+cells	O
+and	O
+are	O
+colocalized	O
+to	O
+synaptic	O
+regions	O
+.	O
+
+We	O
+show	O
+that	O
+a	O
+protein	O
+,	O
+UBC9	B-GENE
+,	O
+interacts	O
+specifically	O
+with	O
+TEL	B-GENE
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+Molecules	O
+of	O
+NH3	O
+are	O
+capable	O
+of	O
+emitting	O
+stimulated	O
+radiation	O
+(	O
+MASER	O
+)	O
+.	O
+
+The	O
+major	O
+findings	O
+of	O
+our	O
+studies	O
+are	O
+as	O
+follows	O
+:	O
+1	O
+)	O
+There	O
+are	O
+no	O
+detectable	O
+signals	O
+around	O
+GDF	B-GENE
+-	I-GENE
+9	I-GENE
+-	O
+deficient	O
+follicles	O
+for	O
+several	O
+theca	O
+cell	O
+layer	O
+markers	O
+[	O
+i	O
+.	O
+e	O
+.	O
+
+Interestingly	O
+,	O
+highly	O
+charged	O
+residues	O
+were	O
+abundantly	O
+possessed	O
+in	O
+the	O
+carboxy	O
+-	O
+terminal	O
+part	O
+of	O
+the	O
+MDV2	B-GENE
+UL10	I-GENE
+protein	I-GENE
+.	O
+
+Identification	O
+and	O
+structure	O
+of	O
+the	O
+Marek	B-GENE
+'	I-GENE
+s	I-GENE
+disease	I-GENE
+virus	I-GENE
+serotype	I-GENE
+2	I-GENE
+glycoprotein	I-GENE
+M	I-GENE
+gene	I-GENE
+:	O
+comparison	O
+with	O
+glycoprotein	B-GENE
+M	I-GENE
+genes	I-GENE
+of	O
+Herpesviridae	O
+family	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+perform	O
+a	O
+cost	O
+-	O
+effectiveness	O
+analysis	O
+(	O
+CEA	O
+)	O
+between	O
+a	O
+standard	O
+antiemetic	O
+regimen	O
+-	O
+chlorpromazine	O
++	O
+dexamethasone	O
+(	O
+CPM	O
+-	O
+DEX	O
+)	O
+-	O
+and	O
+a	O
+5	B-GENE
+-	I-GENE
+HT3	I-GENE
+receptor	I-GENE
+antagonist	O
+-	O
+tropisetron	O
+(	O
+TROP	O
+)	O
+-	O
+-	O
+in	O
+the	O
+control	O
+of	O
+acute	O
+emesis	O
+induced	O
+by	O
+highly	O
+emetogenic	O
+chemotherapy	O
+in	O
+children	O
+,	O
+considering	O
+two	O
+analytic	O
+perspectives	O
+:	O
+hospital	O
+and	O
+patients	O
+.	O
+
+Baseline	O
+data	O
+were	O
+obtained	O
+from	O
+10	O
+adults	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+nucleotide	O
+and	O
+deduced	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+core	O
+regions	O
+of	O
+the	O
+RNA	B-GENE
+-	I-GENE
+dependent	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+domains	I-GENE
+found	O
+in	O
+these	O
+three	O
+dsRNAs	O
+suggested	O
+that	O
+these	O
+dsRNAs	O
+probably	O
+evolved	O
+independently	O
+within	O
+each	O
+host	O
+plant	O
+from	O
+a	O
+common	O
+ancestor	O
+.	O
+
+Consistent	O
+with	O
+this	O
+possibility	O
+,	O
+a	O
+non	O
+-	O
+MBD	B-GENE
+region	O
+of	O
+Bin1	B-GENE
+was	O
+sufficient	O
+to	O
+recruit	O
+a	O
+repression	O
+function	O
+to	O
+DNA	O
+that	O
+was	O
+unrelated	O
+to	O
+histone	B-GENE
+deacetylase	I-GENE
+.	O
+
+Forty	O
+-	O
+eight	O
+sequences	O
+,	O
+30	O
+not	O
+previously	O
+identified	O
+as	O
+IR	O
+-	O
+responsive	O
+,	O
+were	O
+significantly	O
+regulated	O
+by	O
+IR	O
+.	O
+
+A	O
+recently	O
+described	O
+protein	O
+,	O
+metaxin	B-GENE
+1	I-GENE
+,	O
+serves	O
+as	O
+a	O
+component	O
+of	O
+a	O
+preprotein	O
+import	O
+complex	O
+in	O
+the	O
+outer	O
+membrane	O
+of	O
+the	O
+mammalian	O
+mitochondrion	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+rat	B-GENE
+SH2	I-GENE
+-	I-GENE
+containing	I-GENE
+inositol	I-GENE
+phosphatase	I-GENE
+2	I-GENE
+(	O
+SHIP2	B-GENE
+)	O
+and	O
+its	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+insulin	B-GENE
+signaling	O
+.	O
+
+Slp1	B-GENE
+represses	O
+transcription	O
+via	O
+this	O
+binding	O
+site	O
+in	O
+yeast	O
+cells	O
+,	O
+consistent	O
+with	O
+its	O
+role	O
+as	O
+a	O
+direct	O
+repressor	O
+of	O
+ftz	B-GENE
+stripes	O
+in	O
+interstripe	O
+regions	O
+during	O
+late	O
+stages	O
+of	O
+embryogenesis	O
+.	O
+
+The	O
+results	O
+of	O
+these	O
+studies	O
+support	O
+a	O
+model	O
+in	O
+which	O
+VirB4	B-GENE
+dimers	I-GENE
+or	O
+homomultimers	O
+contribute	O
+structural	O
+information	O
+for	O
+the	O
+assembly	O
+of	O
+a	O
+transenvelope	O
+channel	O
+competent	O
+for	O
+bidirectional	O
+DNA	O
+transfer	O
+,	O
+whereas	O
+an	O
+ATP	O
+-	O
+dependent	O
+activity	O
+is	O
+required	O
+for	O
+configuring	O
+this	O
+channel	O
+as	O
+a	O
+dedicated	O
+export	O
+machine	O
+.	O
+
+The	O
+penicillin	B-GENE
+binding	I-GENE
+proteins	I-GENE
+(	O
+PBPs	B-GENE
+)	O
+synthesize	O
+and	O
+remodel	O
+peptidoglycan	O
+,	O
+the	O
+structural	O
+component	O
+of	O
+the	O
+bacterial	O
+cell	O
+wall	O
+.	O
+
+TCR	B-GENE
+alpha	I-GENE
+(	O
+TCRA	B-GENE
+)	O
+expression	O
+was	O
+examined	O
+in	O
+RNA	O
+samples	O
+from	O
+PBMC	O
+and	O
+isolated	O
+populations	O
+of	O
+CD4	B-GENE
++	I-GENE
+,	O
+CD8	B-GENE
++	I-GENE
+,	O
+and	O
+DN	O
+T	O
+cells	O
+from	O
+15	O
+healthy	O
+individuals	O
+.	O
+
+Similar	O
+results	O
+were	O
+obtained	O
+with	O
+xylitol	O
+,	O
+an	O
+activator	O
+of	O
+the	O
+pentose	O
+phosphate	O
+pathway	O
+.	O
+
+D3S1261	B-GENE
+is	O
+physically	O
+located	O
+at	O
+or	O
+near	O
+the	O
+MITF	B-GENE
+locus	I-GENE
+,	O
+while	O
+D3S2465	B-GENE
+and	O
+D3S1766	B-GENE
+are	O
+flanking	O
+the	O
+locus	O
+at	O
+about	O
+17	O
+.	O
+5	O
+cM	O
+genetic	O
+distance	O
+each	O
+side	O
+.	O
+
+The	O
+percentages	O
+of	O
+recovery	O
+decreased	O
+with	O
+storage	O
+time	O
+,	O
+although	O
+the	O
+addition	O
+of	O
+dispersant	O
+(	O
+Tris	O
+-	O
+Tween	O
+80	O
+)	O
+before	O
+storage	O
+appeared	O
+to	O
+partially	O
+prevent	O
+adhesion	O
+.	O
+
+Point	O
+mutations	O
+of	O
+the	O
+site	O
+that	O
+suppressed	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+binding	O
+in	O
+vitro	O
+restored	O
+full	O
+tiGH	B-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+A	O
+human	B-GENE
+Raf	I-GENE
+-	I-GENE
+responsive	I-GENE
+zinc	I-GENE
+-	I-GENE
+finger	I-GENE
+protein	I-GENE
+that	O
+binds	O
+to	O
+divergent	O
+sequences	O
+.	O
+
+We	O
+are	O
+reporting	O
+an	O
+autopsy	O
+case	O
+of	O
+so	O
+-	O
+called	O
+"	O
+acute	O
+multiple	O
+sclerosis	O
+"	O
+that	O
+was	O
+difficult	O
+to	O
+differentiate	O
+from	O
+a	O
+brain	O
+tumor	O
+on	O
+MRI	O
+findings	O
+.	O
+
+Furthermore	O
+,	O
+MOM	B-GENE
+-	I-GENE
+4	I-GENE
+and	O
+TAK1	B-GENE
+bind	O
+related	O
+proteins	O
+that	O
+promote	O
+their	O
+kinase	O
+activities	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+MAZE	O
+-	O
+III	O
+is	O
+the	O
+surgical	O
+treatment	O
+of	O
+choice	O
+for	O
+medically	O
+refractory	O
+atrial	O
+fibrillation	O
+.	O
+
+Gab2	B-GENE
+,	O
+a	O
+new	O
+pleckstrin	B-GENE
+homology	O
+domain	O
+-	O
+containing	O
+adapter	O
+protein	O
+,	O
+acts	O
+to	O
+uncouple	O
+signaling	O
+from	O
+ERK	B-GENE
+kinase	I-GENE
+to	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+The	O
+presence	O
+of	O
+cutaneous	O
+xanthomas	O
+with	O
+normal	O
+serum	O
+lipid	O
+levels	O
+is	O
+due	O
+to	O
+the	O
+antibetalipoproteic	O
+activity	O
+of	O
+the	O
+monoclonal	B-GENE
+immunoglobulin	I-GENE
+.	O
+
+In	O
+an	O
+attempt	O
+to	O
+reduce	O
+the	O
+incidence	O
+of	O
+NSAID	O
+-	O
+induced	O
+gastrointestinal	O
+lesions	O
+,	O
+the	O
+following	O
+approaches	O
+have	O
+been	O
+proposed	O
+:	O
+(	O
+i	O
+)	O
+use	O
+of	O
+the	O
+prostaglandin	O
+analogue	O
+misoprostol	O
+,	O
+which	O
+is	O
+an	O
+antiulcer	O
+drug	O
+which	O
+has	O
+been	O
+proven	O
+to	O
+be	O
+as	O
+effective	O
+in	O
+the	O
+prevention	O
+of	O
+NSAID	O
+-	O
+induced	O
+gastric	O
+and	O
+duodenal	O
+ulcers	O
+as	O
+in	O
+the	O
+reduction	O
+of	O
+serious	O
+upper	O
+gastrointestinal	O
+complications	O
+;	O
+(	O
+ii	O
+)	O
+histamine	B-GENE
+H2	I-GENE
+receptor	I-GENE
+antagonists	O
+(	O
+H2	O
+antagonists	O
+)	O
+,	O
+e	O
+.	O
+g	O
+.	O
+ranitidine	O
+,	O
+cimetidine	O
+and	O
+famotidine	O
+,	O
+which	O
+are	O
+useful	O
+in	O
+the	O
+prevention	O
+of	O
+NSAID	O
+-	O
+induced	O
+duodenal	O
+ulcers	O
+during	O
+long	O
+term	O
+treatment	O
+,	O
+but	O
+not	O
+in	O
+the	O
+prevention	O
+of	O
+NSAID	O
+-	O
+induced	O
+gastric	O
+ulcers	O
+;	O
+(	O
+iii	O
+)	O
+proton	O
+pump	O
+inhibitors	O
+,	O
+e	O
+.	O
+g	O
+omeprazole	O
+,	O
+and	O
+pantoprazole	O
+,	O
+whose	O
+efficacy	O
+in	O
+preventing	O
+NSAID	O
+-	O
+associated	O
+ulcers	O
+has	O
+been	O
+recently	O
+demonstrated	O
+;	O
+and	O
+(	O
+iv	O
+)	O
+barrier	O
+agents	O
+,	O
+e	O
+.	O
+g	O
+.	O
+sucralfate	O
+,	O
+which	O
+cannot	O
+be	O
+recommended	O
+as	O
+prophylactic	O
+agents	O
+to	O
+prevent	O
+NSAID	O
+-	O
+induced	O
+gastropathy	O
+.	O
+
+Lung	O
+mesenchyme	O
+serves	O
+as	O
+a	O
+'	O
+compleat	O
+'	O
+inducer	O
+of	O
+lung	O
+morphogenesis	O
+by	O
+secreting	O
+soluble	O
+peptide	O
+growth	O
+factors	O
+.	O
+
+The	O
+activation	O
+of	O
+the	O
+HIV	O
+promoter	O
+required	O
+the	O
+nuclear	O
+localization	O
+of	O
+c	B-GENE
+-	I-GENE
+Abl	I-GENE
+and	O
+could	O
+be	O
+correlated	O
+with	O
+increased	O
+tyrosine	O
+phosphorylation	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+.	O
+
+The	O
+bovine	B-GENE
+papillomavirus	I-GENE
+E2	I-GENE
+protein	I-GENE
+can	O
+inhibit	O
+the	O
+proliferation	O
+of	O
+HT	O
+-	O
+3	O
+cells	O
+,	O
+a	O
+p53	B-GENE
+-	O
+negative	O
+cervical	O
+carcinoma	O
+cell	O
+line	O
+containing	O
+integrated	O
+human	O
+papillomavirus	O
+type	O
+30	O
+DNA	O
+.	O
+
+E2	B-GENE
+point	O
+mutants	O
+unable	O
+to	O
+inhibit	O
+cell	O
+growth	O
+did	O
+not	O
+repress	O
+cdc25A	B-GENE
+and	O
+cdc25B	B-GENE
+expression	O
+,	O
+nor	O
+did	O
+the	O
+cell	O
+cycle	O
+inhibitors	O
+hydroxyurea	O
+and	O
+mimosine	O
+.	O
+
+BACKGROUND	O
+/	O
+PURPOSE	O
+:	O
+Anomalous	O
+arrangement	O
+of	O
+the	O
+pancreaticobiliary	O
+duct	O
+(	O
+AAPBD	O
+)	O
+is	O
+closely	O
+related	O
+to	O
+congenital	O
+biliary	O
+dilatation	O
+and	O
+frequently	O
+associated	O
+with	O
+biliary	O
+tract	O
+malignancy	O
+.	O
+
+Neurospora	O
+crassa	O
+CYT	B-GENE
+-	I-GENE
+18	I-GENE
+,	O
+can	O
+rescue	O
+the	O
+exonic	O
+trap	O
+and	O
+intron	O
+mutants	O
+which	O
+cause	O
+a	O
+structural	O
+defect	O
+.	O
+
+DDP1	B-GENE
+also	O
+localizes	O
+to	O
+heterochromatin	O
+in	O
+interphase	O
+nuclei	O
+of	O
+larval	O
+neuroblasts	O
+.	O
+
+In	O
+a	O
+reconstituted	O
+human	O
+DNA	O
+repair	O
+system	O
+containing	O
+DNA	B-GENE
+polymerase	I-GENE
+beta	I-GENE
+and	O
+DNA	B-GENE
+ligase	I-GENE
+III	I-GENE
+-	O
+XRCC1	B-GENE
+,	O
+accurate	O
+rejoining	O
+of	O
+a	O
+3	O
+'	O
+mismatched	O
+base	O
+residue	O
+at	O
+a	O
+single	O
+-	O
+strand	O
+break	O
+is	O
+dependent	O
+on	O
+addition	O
+of	O
+the	O
+exonuclease	O
+.	O
+
+The	O
+PAC	O
+clone	O
+with	O
+an	O
+insert	O
+size	O
+of	O
+120kb	O
+was	O
+isolated	O
+and	O
+mapped	O
+by	O
+restriction	O
+analysis	O
+.	O
+
+Sequence	O
+of	O
+10q24	B-GENE
+locus	I-GENE
+surrounding	O
+the	O
+HOX11	B-GENE
+oncogene	I-GENE
+reveals	O
+a	O
+new	O
+gene	O
+HUG1	B-GENE
+expressed	O
+in	O
+a	O
+T	O
+-	O
+ALL	O
+cell	O
+line	O
+.	O
+
+About	O
+20	O
+kb	O
+upstream	O
+of	O
+LAMB2	B-GENE
+we	O
+found	O
+a	O
+gene	O
+encoding	O
+a	O
+transcribed	O
+,	O
+non	O
+-	O
+processed	O
+LAMB2	B-GENE
+-	I-GENE
+like	I-GENE
+pseudogene	I-GENE
+(	O
+LAMB2L	B-GENE
+)	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+of	O
+the	O
+R2	B-GENE
+protein	I-GENE
+was	O
+used	O
+to	O
+provide	O
+evidence	O
+that	O
+this	O
+motif	O
+is	O
+also	O
+part	O
+of	O
+the	O
+active	O
+site	O
+of	O
+the	O
+endonuclease	O
+encoded	O
+by	O
+this	O
+element	O
+.	O
+
+The	O
+infected	B-GENE
+cell	I-GENE
+protein	I-GENE
+no	I-GENE
+.	I-GENE
+0	I-GENE
+(	O
+ICP0	B-GENE
+)	O
+of	O
+herpes	O
+simplex	O
+virus	O
+1	O
+is	O
+a	O
+promiscuous	O
+transactivator	O
+shown	O
+to	O
+enhance	O
+the	O
+expression	O
+of	O
+genes	O
+introducted	O
+into	O
+cells	O
+by	O
+infection	O
+or	O
+transfection	O
+.	O
+
+Wrist	O
+measurement	O
+of	O
+blood	O
+pressure	O
+:	O
+some	O
+critical	O
+remarks	O
+to	O
+oscillometry	O
+.	O
+
+G	O
+-	O
+box	O
+-	O
+directed	O
+expression	O
+in	O
+leaves	O
+required	O
+the	O
+presence	O
+of	O
+an	O
+enhancer	O
+region	O
+from	O
+the	O
+cauliflower	O
+mosaic	O
+virus	O
+(	O
+CaMV	O
+)	O
+35S	B-GENE
+promoter	I-GENE
+.	O
+
+Another	O
+element	O
+necessary	O
+for	O
+augmenting	O
+the	O
+amplitude	O
+of	O
+the	O
+oscillation	O
+lies	O
+between	O
+-	O
+178	O
+and	O
+-	O
+264	O
+.	O
+
+This	O
+scFv	O
+was	O
+therefore	O
+used	O
+as	O
+control	O
+in	O
+experiments	O
+where	O
+another	O
+anti	B-GENE
+-	I-GENE
+Ras	I-GENE
+scFv	I-GENE
+(	O
+Y259	B-GENE
+scFv	I-GENE
+,	O
+derived	O
+from	O
+the	O
+neutralizing	O
+anti	B-GENE
+-	I-GENE
+Ras	I-GENE
+mAb	I-GENE
+Y13	I-GENE
+-	I-GENE
+259	I-GENE
+)	O
+blocked	O
+the	O
+Ras	B-GENE
+pathway	O
+in	O
+vitro	O
+and	O
+led	O
+to	O
+tumor	O
+regression	O
+in	O
+a	O
+nude	O
+mouse	O
+model	O
+[	O
+Cochet	O
+,	O
+O	O
+.	O
+,	O
+Kenigsberg	O
+,	O
+M	O
+.	O
+,	O
+Delumeau	O
+,	O
+I	O
+.	O
+,	O
+Virone	O
+-	O
+Oddos	O
+,	O
+A	O
+.	O
+,	O
+Multon	O
+,	O
+M	O
+.	O
+C	O
+.	O
+,	O
+Fridman	O
+,	O
+W	O
+.	O
+H	O
+.	O
+,	O
+Schweighoffer	O
+,	O
+F	O
+.	O
+,	O
+Teillaud	O
+,	O
+J	O
+.	O
+L	O
+.	O
+,	O
+Tocque	O
+,	O
+B	O
+.	O
+,	O
+1998	O
+.	O
+
+There	O
+was	O
+no	O
+competition	O
+between	O
+activin	B-GENE
+A	I-GENE
+and	O
+OP	B-GENE
+-	I-GENE
+1	I-GENE
+for	O
+availability	O
+of	O
+Smad4	B-GENE
+,	O
+indicating	O
+that	O
+the	O
+concentration	O
+of	O
+this	O
+common	O
+signal	O
+transducer	O
+is	O
+not	O
+limiting	O
+for	O
+generating	O
+the	O
+observed	O
+biological	O
+responses	O
+.	O
+
+Our	O
+data	O
+therefore	O
+indicate	O
+that	O
+it	O
+is	O
+possible	O
+to	O
+engineer	O
+the	O
+HA	B-GENE
+envelope	I-GENE
+glycoprotein	I-GENE
+by	O
+fusing	O
+ligands	O
+to	O
+its	O
+amino	O
+-	O
+terminal	O
+end	O
+without	O
+affecting	O
+its	O
+fusion	O
+activity	O
+.	O
+
+However	O
+,	O
+the	O
+favored	O
+,	O
+parallel	O
+beta	O
+helix	O
+model	O
+is	O
+a	O
+compact	O
+coil	O
+of	O
+ten	O
+helically	O
+arranged	O
+beta	O
+strands	O
+forming	O
+two	O
+parallel	O
+beta	O
+sheet	O
+faces	O
+.	O
+
+This	O
+is	O
+predicted	O
+to	O
+encode	O
+a	O
+315	O
+-	O
+residue	O
+protein	O
+containing	O
+seven	O
+hydrophobic	O
+helical	O
+regions	O
+and	O
+a	O
+17	O
+amino	O
+acid	O
+motif	O
+characteristic	O
+of	O
+the	O
+R7G	B-GENE
+family	I-GENE
+of	O
+G	B-GENE
+-	I-GENE
+protein	I-GENE
+coupled	I-GENE
+membrane	I-GENE
+-	I-GENE
+bound	I-GENE
+receptors	I-GENE
+.	O
+
+Characterisation	O
+of	O
+the	O
+chicken	B-GENE
+apolipoprotein	I-GENE
+A	I-GENE
+-	I-GENE
+I	I-GENE
+gene	I-GENE
+5	O
+'	O
+-	O
+flanking	O
+region	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+members	O
+of	O
+the	O
+ATF	B-GENE
+family	I-GENE
+are	O
+involved	O
+in	O
+mediating	O
+the	O
+transcriptional	O
+regulation	O
+of	O
+the	O
+KGF	B-GENE
+gene	I-GENE
+in	O
+response	O
+to	O
+extracellular	O
+stimuli	O
+via	O
+a	O
+novel	O
+CRE	O
+regulatory	O
+element	O
+.	O
+
+Moreover	O
+,	O
+a	O
+high	O
+proportion	O
+of	O
+blood	O
+samples	O
+from	O
+a	O
+random	O
+sample	O
+of	O
+the	O
+rest	O
+of	O
+the	O
+suspects	O
+tested	O
+positive	O
+for	O
+trypanosome	O
+-	O
+specific	O
+DNA	O
+by	O
+PCR	O
+(	O
+79	O
+.	O
+9	O
+%	O
+for	O
+T	O
+.	O
+b	O
+.	O
+gambiense	O
+and	O
+13	O
+.	O
+9	O
+%	O
+for	O
+T	O
+.	O
+b	O
+.	O
+rhodesiense	O
+)	O
+.	O
+
+A	O
+multi	O
+-	O
+centre	O
+evaluation	O
+of	O
+the	O
+card	O
+indirect	O
+agglutination	O
+test	O
+for	O
+trypanosomiasis	O
+(	O
+TrypTect	O
+CIATT	O
+)	O
+.	O
+
+Results	O
+for	O
+men	O
+who	O
+drank	O
+up	O
+to	O
+two	O
+drinks	O
+per	O
+day	O
+suggest	O
+that	O
+if	O
+the	O
+dependence	O
+criteria	O
+were	O
+invalid	O
+,	O
+reductions	O
+in	O
+the	O
+prevalence	O
+of	O
+specific	O
+indicators	O
+of	O
+alcohol	O
+dependence	O
+would	O
+range	O
+from	O
+0	O
+.	O
+3	O
+%	O
+to	O
+5	O
+.	O
+2	O
+%	O
+.	O
+
+Mutagenesis	O
+of	O
+the	O
+CDE	O
+/	O
+CHR	O
+elements	O
+and	O
+Sp1	B-GENE
+sites	I-GENE
+in	O
+this	O
+region	O
+,	O
+alone	O
+or	O
+in	O
+combination	O
+,	O
+reduced	O
+transcriptional	O
+activity	O
+by	O
+40	O
+-	O
+60	O
+%	O
+in	O
+asynchronously	O
+growing	O
+cells	O
+and	O
+abolished	O
+cell	O
+cycle	O
+periodicity	O
+in	O
+G2	O
+-	O
+M	O
+-	O
+synchronized	O
+cells	O
+.	O
+
+Using	O
+Scheffe	O
+'	O
+s	O
+procedure	O
+as	O
+an	O
+illustration	O
+,	O
+comparisons	O
+are	O
+made	O
+to	O
+usual	O
+sample	O
+size	O
+methods	O
+that	O
+incorrectly	O
+ignore	O
+the	O
+stochastic	O
+nature	O
+of	O
+S2p	O
+.	O
+
+The	O
+crystal	O
+structure	O
+of	O
+the	O
+VP16	B-GENE
+core	I-GENE
+has	O
+been	O
+determined	O
+at	O
+2	O
+.	O
+1	O
+A	O
+resolution	O
+.	O
+
+The	O
+latter	O
+method	O
+adds	O
+clamping	O
+of	O
+the	O
+inferior	O
+vena	O
+cava	O
+,	O
+which	O
+results	O
+in	O
+hypotension	O
+,	O
+requiring	O
+invasive	O
+anesthetic	O
+management	O
+.	O
+
+By	O
+contrast	O
+,	O
+PvirE	B-GENE
+or	O
+Plac	B-GENE
+promoter	I-GENE
+constructs	I-GENE
+yielded	O
+functional	O
+VirE2	B-GENE
+only	O
+if	O
+virE1	B-GENE
+was	O
+coexpressed	O
+with	O
+virE2	B-GENE
+.	O
+
+Simian	O
+parainfluenza	O
+virus	O
+5	O
+(	O
+SV5	O
+)	O
+is	O
+a	O
+prototype	O
+of	O
+the	O
+Paramyxoviridae	O
+family	O
+of	O
+nonsegmented	O
+negative	O
+-	O
+sense	O
+RNA	O
+viruses	O
+.	O
+
+To	O
+investigate	O
+the	O
+functions	O
+of	O
+GE	O
+,	O
+IG	O
+,	O
+and	O
+GS	O
+sequences	O
+in	O
+transcription	O
+,	O
+we	O
+constructed	O
+plasmids	O
+containing	O
+cDNAs	O
+of	O
+the	O
+full	O
+-	O
+length	O
+SV5	O
+genome	O
+in	O
+which	O
+the	O
+gene	O
+junction	O
+sequences	O
+(	O
+GE	O
+,	O
+IG	O
+,	O
+and	O
+GS	O
+sequences	O
+)	O
+located	O
+between	O
+the	O
+hemagglutinin	B-GENE
+-	I-GENE
+neuraminidase	I-GENE
+(	O
+HN	B-GENE
+)	O
+and	O
+the	O
+polymerase	B-GENE
+(	I-GENE
+L	I-GENE
+)	I-GENE
+genes	I-GENE
+were	O
+replaced	O
+with	O
+the	O
+counterpart	O
+sequences	O
+from	O
+other	O
+gene	O
+junctions	O
+.	O
+
+CXCR4	B-GENE
+is	O
+a	O
+chemokine	O
+receptor	O
+and	O
+a	O
+coreceptor	O
+for	O
+T	O
+-	O
+cell	O
+-	O
+line	O
+-	O
+tropic	O
+(	O
+X4	O
+)	O
+and	O
+dual	O
+-	O
+tropic	O
+(	O
+R5X4	O
+)	O
+human	O
+immunodeficiency	O
+virus	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+isolates	O
+.	O
+
+These	O
+data	O
+will	O
+help	O
+us	O
+to	O
+better	O
+detail	O
+the	O
+CXCR4	B-GENE
+structural	O
+requirements	O
+exhibited	O
+by	O
+different	O
+HIV	O
+-	O
+1	O
+strains	O
+and	O
+will	O
+direct	O
+further	O
+mutagenesis	O
+efforts	O
+aimed	O
+at	O
+better	O
+defining	O
+the	O
+domains	O
+in	O
+CXCR4	B-GENE
+involved	O
+in	O
+the	O
+HIV	O
+-	O
+1	O
+Env	B-GENE
+-	O
+mediated	O
+fusion	O
+process	O
+.	O
+
+The	O
+results	O
+of	O
+these	O
+analyses	O
+indicate	O
+that	O
+the	O
+proteinase	O
+cleaves	O
+at	O
+amino	O
+acid	O
+residues	O
+E960	O
+-	O
+A961	O
+,	O
+E1071	O
+-	O
+S1072	O
+,	O
+E1345	O
+-	O
+T1346	O
+,	O
+and	O
+E1419	O
+-	O
+G1420	O
+;	O
+however	O
+,	O
+the	O
+cleavage	O
+efficiency	O
+is	O
+varied	O
+.	O
+
+y	O
+.	O
+
+SM	B-GENE
+is	O
+also	O
+shown	O
+to	O
+be	O
+associated	O
+in	O
+vivo	O
+with	O
+other	O
+components	O
+of	O
+the	O
+CRM	B-GENE
+1	I-GENE
+export	O
+pathway	O
+,	O
+including	O
+the	O
+small	B-GENE
+GTPase	I-GENE
+Ran	I-GENE
+and	O
+the	O
+nucleoporin	O
+CAN	B-GENE
+/	O
+Nup214	B-GENE
+.	O
+
+Identification	O
+of	O
+a	O
+spliced	O
+gene	O
+from	O
+Kaposi	O
+'	O
+s	O
+sarcoma	O
+-	O
+associated	O
+herpesvirus	O
+encoding	O
+a	O
+protein	O
+with	O
+similarities	O
+to	O
+latent	B-GENE
+membrane	I-GENE
+proteins	I-GENE
+1	I-GENE
+and	I-GENE
+2A	I-GENE
+of	I-GENE
+Epstein	I-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+.	O
+
+Auditory	O
+clicks	O
+were	O
+given	O
+at	O
+a	O
+rate	O
+of	O
+20	O
+s	O
+(	O
+-	O
+1	O
+)	O
+.	O
+
+Myosin	B-GENE
+light	I-GENE
+chain	I-GENE
+kinase	I-GENE
+functions	O
+downstream	O
+of	O
+Ras	B-GENE
+/	O
+ERK	B-GENE
+to	O
+promote	O
+migration	O
+of	O
+urokinase	B-GENE
+-	I-GENE
+type	I-GENE
+plasminogen	I-GENE
+activator	I-GENE
+-	O
+stimulated	O
+cells	O
+in	O
+an	O
+integrin	B-GENE
+-	O
+selective	O
+manner	O
+.	O
+
+The	O
+inhibition	O
+of	O
+StAR	B-GENE
+gene	I-GENE
+transcription	O
+by	O
+DAX	B-GENE
+-	I-GENE
+1	I-GENE
+was	O
+dose	O
+-	O
+dependent	O
+reducing	O
+transcription	O
+to	O
+6	O
+%	O
+of	O
+control	O
+levels	O
+.	O
+
+In	O
+a	O
+prospective	O
+randomized	O
+study	O
+,	O
+287	O
+patients	O
+with	O
+advanced	O
+non	O
+-	O
+small	O
+cell	O
+lung	O
+cancer	O
+(	O
+NSCLC	O
+)	O
+stage	O
+IIIb	O
+or	O
+IV	O
+with	O
+ECOG	O
+performance	O
+status	O
+(	O
+PS	O
+)	O
+0	O
+-	O
+1	O
+or	O
+2	O
+were	O
+randomly	O
+assigned	O
+to	O
+receive	O
+either	O
+best	O
+supportive	O
+care	O
+(	O
+BSC	O
+)	O
+or	O
+supportive	O
+care	O
+plus	O
+combination	O
+chemotherapy	O
+(	O
+IEP	O
+regimen	O
+:	O
+ifosfamide	O
+3	O
+gm	O
+/	O
+m2	O
+IV	O
+with	O
+mesna	O
+uroprotection	O
+,	O
+epirubicin	O
+60	O
+mg	O
+/	O
+m2	O
+IV	O
+on	O
+day	O
+1	O
+and	O
+cisplatin	O
+60	O
+mg	O
+/	O
+m2	O
+IV	O
+on	O
+day	O
+2	O
+;	O
+or	O
+MVP	O
+regimen	O
+:	O
+mitomycin	O
+-	O
+C	O
+8	O
+mg	O
+/	O
+m2	O
+,	O
+cisplatin	O
+100	O
+mg	O
+/	O
+m2	O
+IV	O
+on	O
+day	O
+1	O
+,	O
+vinblastine	O
+4	O
+mg	O
+/	O
+m2	O
+IV	O
+on	O
+days	O
+1	O
+and	O
+15	O
+)	O
+.	O
+
+The	O
+transcriptional	O
+activities	O
+of	O
+the	O
+full	O
+-	O
+length	O
+promoter	O
+(	O
+-	O
+295	O
+to	O
++	O
+85	O
+)	O
+and	O
+of	O
+three	O
+deletion	O
+constructs	O
+(	O
+-	O
+197	O
+,	O
+-	O
+154	O
+and	O
+-	O
+74	O
+to	O
++	O
+85	O
+)	O
+were	O
+significantly	O
+down	O
+-	O
+regulated	O
+in	O
+resistant	O
+cells	O
+.	O
+
+A	O
+13	O
+-	O
+bp	O
+cis	O
+-	O
+regulatory	O
+element	O
+in	O
+the	O
+LTR	O
+promoter	O
+of	O
+the	O
+tobacco	B-GENE
+retrotransposon	I-GENE
+Tto1	I-GENE
+is	O
+involved	O
+in	O
+responsiveness	O
+to	O
+tissue	O
+culture	O
+,	O
+wounding	O
+,	O
+methyl	O
+jasmonate	O
+and	O
+fungal	O
+elicitors	O
+.	O
+
+In	O
+this	O
+study	O
+we	O
+describe	O
+that	O
+platelet	B-GENE
+-	I-GENE
+derived	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+PDGF	B-GENE
+)	O
+,	O
+12	O
+-	O
+O	O
+-	O
+tetradecanoyl	O
+-	O
+phorbol	O
+-	O
+acetate	O
+(	O
+TPA	O
+)	O
+,	O
+and	O
+forskolin	O
+induced	O
+CREB	B-GENE
+(	O
+cAMP	B-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+)	O
+Ser	O
+-	O
+133	O
+phosphorylation	O
+with	O
+comparable	O
+magnitude	O
+and	O
+kinetics	O
+in	O
+NIH	O
+3T3	O
+cells	O
+.	O
+
+This	O
+constitutes	O
+evidence	O
+for	O
+an	O
+in	O
+vivo	O
+role	O
+of	O
+SRC	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+dimerization	O
+-	O
+induced	O
+activation	O
+by	O
+OR1	B-GENE
+/	O
+RXRalpha	B-GENE
+.	O
+
+By	O
+contrast	O
+,	O
+mTRAP100	B-GENE
+coprecipitates	O
+in	O
+vivo	O
+with	O
+another	O
+component	O
+of	O
+the	O
+TRAP	B-GENE
+complex	I-GENE
+(	O
+TRAP220	B-GENE
+)	O
+,	O
+which	O
+directly	O
+contacts	O
+TR	B-GENE
+and	O
+the	O
+vitamin	B-GENE
+D	I-GENE
+receptor	I-GENE
+in	O
+a	O
+ligand	O
+-	O
+dependent	O
+manner	O
+.	O
+
+This	O
+sequence	O
+also	O
+confers	O
+VDR	B-GENE
+and	O
+vitamin	O
+D	O
+responsiveness	O
+to	O
+a	O
+heterologous	O
+promoter	O
+.	O
+
+Expression	O
+of	O
+GlcNAc	B-GENE
+-	I-GENE
+TI	I-GENE
+mRNA	I-GENE
+in	O
+tobacco	O
+leaves	O
+was	O
+detected	O
+using	O
+RT	O
+-	O
+PCR	O
+.	O
+
+Chemical	O
+stability	O
+tests	O
+and	O
+site	O
+-	O
+specific	O
+mutagenesis	O
+identified	O
+amino	O
+acids	O
+H219	O
+and	O
+D63	O
+of	O
+RegS	B-GENE
+and	O
+RegR	B-GENE
+,	O
+respectively	O
+,	O
+as	O
+the	O
+phosphorylated	O
+residues	O
+.	O
+
+An	O
+overexpression	O
+of	O
+the	O
+betaAPP	B-GENE
+gene	I-GENE
+in	O
+certain	O
+areas	O
+of	O
+the	O
+AD	O
+brain	O
+has	O
+been	O
+suggested	O
+to	O
+be	O
+an	O
+important	O
+factor	O
+in	O
+the	O
+neuropathology	O
+of	O
+AD	O
+.	O
+
+For	O
+functional	O
+studies	O
+,	O
+two	O
+promoter	O
+regions	O
+were	O
+cloned	O
+upstream	O
+of	O
+the	O
+reporter	O
+gene	O
+,	O
+chloramphenicol	B-GENE
+acetyl	I-GENE
+transferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+:	O
+(	O
+i	O
+)	O
+phbetaE	O
+-	O
+B	O
+-	O
+the	O
+plasmid	O
+that	O
+contains	O
+the	O
+human	O
+(	O
+h	O
+)	O
+promoter	O
+region	O
+(	O
+-	O
+2832	O
+to	O
++	O
+101	O
+)	O
+including	O
+URE	O
+,	O
+and	O
+(	O
+ii	O
+)	O
+prhbetaE	O
+-	O
+B	O
+-	O
+the	O
+plasmid	O
+that	O
+contains	O
+the	O
+rhesus	O
+(	O
+rh	O
+)	O
+promoter	O
+region	O
+excluding	O
+URE	O
+as	O
+it	O
+lacks	O
+a	O
+270	O
+bp	O
+region	O
+of	O
+the	O
+hbetaAPP	B-GENE
+promoter	I-GENE
+(	O
+-	O
+2435	O
+to	O
+-	O
+2165	O
+)	O
+.	O
+
+67	O
+393	O
+bp	O
+of	O
+contiguous	O
+DNA	O
+located	O
+between	O
+markers	O
+cdc18	B-GENE
+and	O
+cdc14	B-GENE
+on	O
+the	O
+right	O
+arm	O
+of	O
+fission	O
+yeast	O
+chromosome	O
+II	O
+has	O
+been	O
+sequenced	O
+as	O
+part	O
+of	O
+the	O
+European	O
+Union	O
+Schizosaccharomyces	O
+pombe	O
+genome	O
+sequencing	O
+project	O
+.	O
+
+67	O
+393	O
+bp	O
+of	O
+contiguous	O
+DNA	O
+located	O
+between	O
+markers	O
+cdc18	B-GENE
+and	O
+cdc14	B-GENE
+on	O
+the	O
+right	O
+arm	O
+of	O
+fission	O
+yeast	O
+chromosome	O
+II	O
+has	O
+been	O
+sequenced	O
+as	O
+part	O
+of	O
+the	O
+European	O
+Union	O
+Schizosaccharomyces	O
+pombe	O
+genome	O
+sequencing	O
+project	O
+.	O
+
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+(	O
+480	O
+micrograms	O
+subcutaneously	O
+(	O
+s	O
+.	O
+c	O
+.	O
+)	O
+)	O
+were	O
+used	O
+in	O
+55	O
+and	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+(	O
+400	O
+micrograms	O
+s	O
+.	O
+c	O
+.	O
+)	O
+in	O
+28	O
+chemotherapeutic	O
+cycles	O
+.	O
+
+Overexpression	O
+of	O
+H411	B-GENE
+cDNA	I-GENE
+in	O
+the	O
+RAW	O
+264	O
+.	O
+7	O
+macrophage	O
+cell	O
+line	O
+promoted	O
+an	O
+increased	O
+growth	O
+rate	O
+,	O
+suggesting	O
+that	O
+expression	O
+of	O
+H411	B-GENE
+is	O
+part	O
+of	O
+the	O
+proliferative	O
+cell	O
+response	O
+to	O
+LPS	O
+.	O
+
+Human	O
+expressed	O
+sequence	O
+tag	O
+clones	O
+were	O
+identified	O
+by	O
+sequence	O
+similarity	O
+to	O
+mammalian	B-GENE
+and	I-GENE
+yeast	I-GENE
+oligosaccharide	I-GENE
+-	I-GENE
+processing	I-GENE
+mannosidases	I-GENE
+,	O
+and	O
+the	O
+full	O
+-	O
+length	O
+coding	O
+region	O
+of	O
+the	O
+putative	O
+mannosidase	B-GENE
+homolog	I-GENE
+was	O
+isolated	O
+by	O
+a	O
+combination	O
+of	O
+5	O
+'	O
+-	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+and	O
+direct	O
+polymerase	O
+chain	O
+reaction	O
+from	O
+human	O
+placental	O
+cDNA	O
+.	O
+
+Activation	O
+of	O
+ERK1	B-GENE
+/	I-GENE
+2	I-GENE
+is	O
+correlated	O
+with	O
+induction	O
+of	O
+the	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+response	I-GENE
+genes	I-GENE
+.	O
+
+The	O
+transcription	O
+of	O
+most	O
+RP	B-GENE
+genes	I-GENE
+is	O
+activated	O
+by	O
+two	O
+Rap1p	B-GENE
+binding	I-GENE
+sites	I-GENE
+,	O
+250	O
+to	O
+400	O
+bp	O
+upstream	O
+from	O
+the	O
+initiation	O
+of	O
+transcription	O
+.	O
+
+We	O
+have	O
+isolated	O
+three	O
+mutant	O
+alleles	O
+of	O
+CDC4	B-GENE
+(	O
+cdc4	B-GENE
+-	I-GENE
+10	I-GENE
+,	O
+cdc4	B-GENE
+-	I-GENE
+11	I-GENE
+,	O
+and	O
+cdc4	B-GENE
+-	I-GENE
+16	I-GENE
+)	O
+which	O
+suppress	O
+the	O
+nuclear	O
+division	O
+defect	O
+of	O
+cdc20	B-GENE
+-	I-GENE
+1	I-GENE
+cells	O
+.	O
+
+Role	O
+of	O
+secondary	O
+structure	O
+in	O
+discrimination	O
+between	O
+constitutive	O
+and	O
+inducible	O
+activators	O
+.	O
+
+In	O
+summary	O
+,	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+-	O
+dependent	O
+activation	O
+of	O
+NO	O
+production	O
+mediates	O
+apoptosis	O
+after	O
+TG	B-GENE
+exposure	O
+in	O
+JT	O
+/	O
+Neo	O
+cells	O
+.	O
+
+Accumulation	O
+of	O
+the	O
+U4	B-GENE
+/	O
+U6	B-GENE
+duplex	O
+was	O
+relieved	O
+by	O
+overexpression	O
+of	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+Prp44p	I-GENE
+.	O
+
+Our	O
+results	O
+,	O
+when	O
+combined	O
+with	O
+previously	O
+published	O
+in	O
+vitro	O
+results	O
+,	O
+support	O
+a	O
+direct	O
+role	O
+for	O
+Prp44p	B-GENE
+in	O
+unwinding	O
+of	O
+the	O
+U4	B-GENE
+/	O
+U6	B-GENE
+helix	O
+.	O
+
+This	O
+approximately	O
+125	O
+-	O
+nt	O
+RNA	O
+proved	O
+to	O
+arise	O
+via	O
+RNase	B-GENE
+E	I-GENE
+cleavage	O
+from	O
+the	O
+3	O
+'	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+mRNAs	O
+bearing	O
+the	O
+terminator	O
+.	O
+
+The	O
+mysteries	O
+of	O
+geographic	O
+variability	O
+in	O
+nonmelanoma	O
+skin	O
+cancer	O
+incidence	O
+.	O
+
+In	O
+Saccharomyces	O
+cerevisiae	O
+the	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinases	I-GENE
+(	O
+PKAs	B-GENE
+)	O
+promote	O
+cytoplasmic	O
+growth	O
+and	O
+modulate	O
+the	O
+growth	O
+-	O
+regulated	O
+mechanism	O
+triggering	O
+the	O
+begin	O
+of	O
+DNA	O
+synthesis	O
+.	O
+
+A	O
+recombinant	O
+derivative	O
+harboring	O
+the	O
+pMJ101	O
+replication	O
+region	O
+proved	O
+to	O
+be	O
+compatible	O
+with	O
+pJM1	O
+,	O
+a	O
+plasmid	O
+containing	O
+the	O
+iron	O
+acquisition	O
+system	O
+required	O
+for	O
+the	O
+virulence	O
+of	O
+V	O
+.	O
+anguillarum	O
+775	O
+,	O
+another	O
+important	O
+pathogen	O
+that	O
+causes	O
+vibriosis	O
+.	O
+
+FAK	B-GENE
+localizes	O
+to	O
+sites	O
+of	O
+transmembrane	B-GENE
+integrin	I-GENE
+receptor	I-GENE
+clustering	O
+and	O
+facilitates	O
+intracellular	O
+signaling	O
+events	O
+.	O
+
+Expression	O
+of	O
+various	O
+FAK	B-GENE
+mutants	I-GENE
+in	O
+the	O
+FAK	B-GENE
+-	O
+cells	O
+showed	O
+that	O
+FAK	B-GENE
+kinase	I-GENE
+activity	O
+,	O
+the	O
+Tyr	B-GENE
+-	I-GENE
+397	I-GENE
+/	I-GENE
+SH2	I-GENE
+domain	I-GENE
+binding	I-GENE
+site	I-GENE
+,	O
+and	O
+the	O
+first	O
+proline	O
+-	O
+rich	O
+SH3	B-GENE
+binding	I-GENE
+region	I-GENE
+in	O
+the	O
+FAK	B-GENE
+C	I-GENE
+-	I-GENE
+terminal	I-GENE
+domain	I-GENE
+were	O
+individually	O
+needed	O
+to	O
+promote	O
+full	O
+FAK	B-GENE
+-	O
+mediated	O
+FAK	B-GENE
+-	O
+cell	O
+migration	O
+to	O
+FN	B-GENE
+whereas	O
+direct	O
+paxillin	B-GENE
+binding	O
+to	O
+FAK	B-GENE
+was	O
+not	O
+required	O
+.	O
+
+This	O
+dominant	O
+-	O
+negative	O
+effect	O
+of	O
+FRNK	B-GENE
+was	O
+reversed	O
+by	O
+a	O
+point	O
+mutation	O
+(	O
+Leu	O
+-	O
+1034	O
+to	O
+Ser	O
+)	O
+which	O
+prevented	O
+FRNK	B-GENE
+localization	O
+to	O
+focal	O
+contact	O
+sites	O
+.	O
+
+Fifty	O
+six	O
+young	O
+patients	O
+(	O
+age	O
+<	O
+45	O
+yr	O
+)	O
+with	O
+doppler	O
+-	O
+proven	O
+DVT	O
+were	O
+investigated	O
+for	O
+the	O
+presence	O
+of	O
+resistance	O
+to	O
+activated	B-GENE
+protein	I-GENE
+C	I-GENE
+(	O
+APC	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+,	O
+lupus	O
+anticoagulant	O
+(	O
+LA	O
+)	O
+,	O
+anticardiolipin	B-GENE
+antibodies	I-GENE
+and	O
+deficiencies	O
+of	O
+protein	B-GENE
+C	I-GENE
+,	O
+protein	B-GENE
+S	I-GENE
+,	O
+ATIII	B-GENE
+activities	O
+.	O
+
+DESIGN	O
+:	O
+Comparison	O
+of	O
+number	O
+of	O
+women	O
+with	O
+PKU	O
+aged	O
+15	O
+-	O
+44	O
+years	O
+on	O
+the	O
+NSW	O
+PKU	O
+database	O
+(	O
+observed	O
+number	O
+)	O
+with	O
+expected	O
+number	O
+derived	O
+from	O
+population	O
+data	O
+.	O
+
+PURPOSE	O
+:	O
+The	O
+purposes	O
+of	O
+the	O
+present	O
+study	O
+were	O
+to	O
+assess	O
+the	O
+effects	O
+of	O
+a	O
+12	O
+-	O
+wk	O
+laboratory	O
+based	O
+aerobic	O
+exercise	O
+program	O
+on	O
+cardiopulmonary	O
+function	O
+,	O
+CD4	B-GENE
+cell	O
+count	O
+,	O
+and	O
+physician	O
+-	O
+assessed	O
+health	O
+status	O
+among	O
+symptomatic	O
+pre	O
+-	O
+AIDS	O
+HIV	O
+-	O
+infected	O
+individuals	O
+(	O
+N	O
+=	O
+28	O
+)	O
+and	O
+to	O
+assess	O
+the	O
+degree	O
+to	O
+which	O
+ill	O
+health	O
+was	O
+associated	O
+with	O
+exercise	O
+relapse	O
+.	O
+
+Epidemiologic	O
+evidence	O
+indicates	O
+that	O
+estrogen	O
+replacement	O
+therapy	O
+after	O
+menopause	O
+increases	O
+breast	O
+cancer	O
+risk	O
+.	O
+
+In	O
+addition	O
+to	O
+its	O
+elongation	O
+activity	O
+,	O
+ELL	B-GENE
+contains	O
+a	O
+novel	O
+type	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+interaction	I-GENE
+domain	I-GENE
+that	O
+is	O
+capable	O
+of	O
+repressing	O
+polymerase	O
+activity	O
+in	O
+promoter	O
+-	O
+specific	O
+transcription	O
+.	O
+
+A	O
+diagnosis	O
+of	O
+IgA	B-GENE
+lambda	I-GENE
+multiple	O
+myeloma	O
+with	O
+peritoneal	O
+involvement	O
+was	O
+made	O
+.	O
+
+The	O
+radiation	O
+burden	O
+associated	O
+with	O
+the	O
+majority	O
+of	O
+examinations	O
+in	O
+nuclear	O
+medicine	O
+expressed	O
+as	O
+the	O
+effective	O
+dose	O
+is	O
+comparable	O
+with	O
+the	O
+radiation	O
+burden	O
+of	O
+radiodiagnostic	O
+examinations	O
+,	O
+only	O
+after	O
+administration	O
+of	O
+preparations	O
+with	O
+131I	O
+,	O
+201Tl	O
+,	O
+67Ga	O
+and	O
+111In	O
+it	O
+is	O
+markedly	O
+higher	O
+.	O
+
+Although	O
+the	O
+risk	O
+of	O
+malformation	O
+in	O
+children	O
+born	O
+after	O
+ICSI	O
+is	O
+not	O
+increased	O
+there	O
+is	O
+an	O
+increased	O
+risk	O
+to	O
+transmit	O
+genetic	O
+abnormalities	O
+in	O
+case	O
+of	O
+NOA	O
+(	O
+such	O
+as	O
+the	O
+rate	O
+of	O
+sex	O
+chromosome	O
+,	O
+or	O
+microdeletions	O
+of	O
+the	O
+Y	O
+chromosome	O
+)	O
+and	O
+in	O
+case	O
+of	O
+congenital	O
+OA	O
+(	O
+mutations	O
+of	O
+the	O
+cystic	B-GENE
+fibrosis	I-GENE
+gene	I-GENE
+)	O
+.	O
+
+TaV	O
+particles	O
+have	O
+a	O
+buoyant	O
+density	O
+of	O
+1	O
+.	O
+296	O
+g	O
+/	O
+cm3	O
+in	O
+CsCl	O
+and	O
+consist	O
+of	O
+two	O
+capsid	B-GENE
+proteins	I-GENE
+of	O
+56	O
+and	O
+6	O
+kDa	O
+.	O
+
+CONCLUSION	O
+:	O
+These	O
+results	O
+suggest	O
+that	O
+vibration	O
+-	O
+induced	O
+neural	O
+involvement	O
+can	O
+be	O
+considered	O
+neither	O
+pure	O
+digital	O
+neuropathy	O
+,	O
+nor	O
+definite	O
+CTS	O
+,	O
+as	O
+previously	O
+described	O
+.	O
+
+In	O
+about	O
+770	O
+bp	O
+upstream	O
+region	O
+of	O
+Spam1	B-GENE
+that	O
+has	O
+been	O
+cloned	O
+and	O
+sequenced	O
+,	O
+multiple	O
+transcription	O
+factor	O
+binding	O
+sites	O
+including	O
+a	O
+CRE	O
+(	O
+cAMP	O
+-	O
+responsive	O
+element	O
+)	O
+were	O
+found	O
+.	O
+
+The	O
+in	O
+vitro	O
+relaxivity	O
+of	O
+the	O
+complex	O
+is	O
+16	O
+.	O
+24	O
+s	O
+(	O
+-	O
+1	O
+)	O
+mM	O
+(	O
+-	O
+1	O
+)	O
+.	O
+
+Bacterial	O
+recovery	O
+of	O
+SA	O
+from	O
+the	O
+liver	O
+/	O
+spleen	O
+and	O
+the	O
+cecal	O
+tonsil	O
+in	O
+contact	O
+poults	O
+and	O
+SG	O
+from	O
+contact	O
+chicks	O
+treated	O
+with	O
+ILK	B-GENE
+was	O
+dramatically	O
+reduced	O
+when	O
+compared	O
+to	O
+non	O
+-	O
+treated	O
+contact	O
+poults	O
+and	O
+chicks	O
+.	O
+
+The	O
+results	O
+of	O
+the	O
+ISIS	O
+-	O
+2	O
+trial	O
+and	O
+the	O
+data	O
+from	O
+the	O
+Antiplatelet	O
+Trialists	O
+'	O
+Collaboration	O
+indicated	O
+that	O
+aspirin	O
+is	O
+mandatory	O
+in	O
+patients	O
+with	O
+acute	O
+myocardial	O
+infarction	O
+and	O
+for	O
+secondary	O
+prevention	O
+.	O
+
+This	O
+study	O
+was	O
+performed	O
+to	O
+assess	O
+the	O
+role	O
+of	O
+additional	O
+diagnostic	O
+laparoscopy	O
+in	O
+the	O
+preoperative	O
+staging	O
+of	O
+patients	O
+with	O
+adenocarcinoma	O
+of	O
+the	O
+esophagus	O
+,	O
+gastric	O
+cancer	O
+and	O
+pancreatic	O
+cancer	O
+prior	O
+to	O
+intended	O
+curative	O
+surgery	O
+.	O
+
+This	O
+report	O
+presents	O
+state	O
+-	O
+specific	O
+MMRs	O
+for	O
+1987	O
+-	O
+1996	O
+,	O
+focusing	O
+on	O
+persistent	O
+disparities	O
+in	O
+maternal	O
+mortality	O
+between	O
+black	O
+and	O
+white	O
+women	O
+.	O
+
+Preheparin	O
+LPL	B-GENE
+mass	O
+level	O
+did	O
+not	O
+significantly	O
+differ	O
+in	O
+individuals	O
+from	O
+19	O
+to	O
+70	O
+years	O
+old	O
+,	O
+for	O
+both	O
+men	O
+and	O
+women	O
+.	O
+
+A	O
+decrease	O
+in	O
+insulin	B-GENE
+-	O
+induced	O
+receptor	O
+kinase	O
+activity	O
+was	O
+observed	O
+for	O
+solubilized	O
+chimeric	O
+receptors	O
+.	O
+
+Cat	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+identical	O
+to	O
+the	O
+recently	O
+identified	O
+binding	O
+partner	O
+for	O
+the	O
+beta	B-GENE
+-	I-GENE
+adrenergic	I-GENE
+receptor	I-GENE
+kinase	I-GENE
+(	O
+betaARK	B-GENE
+or	O
+GRK	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+,	O
+which	O
+was	O
+shown	O
+to	O
+have	O
+Arf	B-GENE
+-	O
+GAP	B-GENE
+activity	O
+.	O
+
+Cat	B-GENE
+proteins	I-GENE
+are	O
+tyrosine	O
+-	O
+phosphorylated	O
+when	O
+co	O
+-	O
+expressed	O
+in	O
+cells	O
+with	O
+the	O
+focal	B-GENE
+adhesion	I-GENE
+kinase	I-GENE
+Fak	B-GENE
+and	O
+Src	B-GENE
+.	O
+
+Immunoprecipitation	O
+experiments	O
+using	O
+DokR	B-GENE
+-	I-GENE
+specific	I-GENE
+antibodies	I-GENE
+revealed	O
+an	O
+interaction	O
+between	O
+endogenous	B-GENE
+DokR	I-GENE
+and	O
+a	O
+150	O
+-	O
+kDa	O
+protein	O
+that	O
+is	O
+tyrosine	O
+-	O
+phosphorylated	O
+in	O
+EGF	B-GENE
+-	O
+stimulated	O
+BaF	O
+/	O
+3	O
+cells	O
+.	O
+
+Expansins	B-GENE
+are	O
+a	O
+family	O
+of	O
+proteins	O
+that	O
+catalyse	O
+long	O
+-	O
+term	O
+extension	O
+of	O
+isolated	O
+plant	O
+cell	O
+walls	O
+due	O
+to	O
+an	O
+as	O
+yet	O
+unknown	O
+biochemical	O
+mechanism	O
+.	O
+
+This	O
+review	O
+summarizes	O
+the	O
+clinical	O
+evidence	O
+to	O
+support	O
+current	O
+therapies	O
+in	O
+irritable	O
+bowel	O
+syndrome	O
+(	O
+IBS	O
+)	O
+.	O
+
+The	O
+responsive	O
+region	O
+of	O
+the	O
+alpha	B-GENE
+2	I-GENE
+(	I-GENE
+V	I-GENE
+)	I-GENE
+collagen	I-GENE
+gene	I-GENE
+was	O
+localized	O
+to	O
+a	O
+fragment	O
+including	O
+100	O
+bp	O
+of	O
+basal	O
+promoter	O
+and	O
+150	O
+bp	O
+of	O
+exon	O
+1	O
+sequences	O
+,	O
+which	O
+contained	O
+two	O
+CRE	O
+-	O
+like	O
+elements	O
+.	O
+
+Furthermore	O
+,	O
+addition	O
+of	O
+B	B-GENE
+-	I-GENE
+Myb	I-GENE
+-	O
+glutathionine	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+fusion	O
+protein	O
+inhibited	O
+complex	O
+formation	O
+.	O
+
+APOE	B-GENE
+-	O
+epsilon4	O
+count	O
+predicts	O
+age	O
+when	O
+prevalence	O
+of	O
+AD	O
+increases	O
+,	O
+then	O
+declines	O
+:	O
+the	O
+Cache	O
+County	O
+Study	O
+.	O
+
+A	O
+new	O
+DNA	B-GENE
+repair	I-GENE
+gene	I-GENE
+from	O
+Schizosaccharomyces	O
+pombe	O
+with	O
+homology	O
+to	O
+RecA	B-GENE
+was	O
+identified	O
+and	O
+characterized	O
+.	O
+
+Among	O
+mucus	O
+-	O
+secreting	O
+cells	O
+,	O
+the	O
+gastric	O
+gland	O
+mucous	O
+cells	O
+,	O
+Brunner	O
+'	O
+s	O
+glands	O
+,	O
+accessory	O
+glands	O
+of	O
+pancreaticobiliary	O
+tract	O
+,	O
+and	O
+pancreatic	O
+ducts	O
+exhibiting	O
+gastric	O
+metaplasia	O
+are	O
+unique	O
+in	O
+that	O
+they	O
+express	O
+class	B-GENE
+III	I-GENE
+mucin	I-GENE
+identified	O
+by	O
+paradoxical	O
+Con	B-GENE
+A	I-GENE
+staining	O
+composed	O
+of	O
+periodate	O
+oxidation	O
+,	O
+sodium	O
+borohydride	O
+reduction	O
+,	O
+Con	B-GENE
+A	I-GENE
+,	O
+and	O
+horseradish	B-GENE
+peroxidase	I-GENE
+reaction	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+mutants	O
+were	O
+strongly	O
+dominant	O
+over	O
+TraR	B-GENE
+,	O
+suggesting	O
+that	O
+they	O
+can	O
+form	O
+heteromultimers	O
+with	O
+the	O
+wild	O
+-	O
+type	O
+activator	O
+.	O
+
+The	O
+data	O
+imply	O
+that	O
+JAK	B-GENE
+/	O
+STAT	B-GENE
+signaling	O
+has	O
+a	O
+role	O
+in	O
+EBV	O
+-	O
+associated	O
+malignancies	O
+.	O
+
+There	O
+were	O
+27	O
+men	O
+and	O
+156	O
+women	O
+.	O
+
+A	O
+.	O
+,	O
+Bowers	O
+,	O
+K	O
+.	O
+E	O
+,	O
+and	O
+Matthews	O
+,	O
+C	O
+.	O
+
+Spfkh1	B-GENE
+is	O
+transcribed	O
+in	O
+one	O
+open	O
+reading	O
+frame	O
+that	O
+contains	O
+the	O
+DNA	O
+binding	O
+domain	O
+,	O
+nuclear	O
+localization	O
+signal	O
+and	O
+transactivation	O
+domain	O
+.	O
+
+The	O
+molecular	O
+mechanism	O
+of	O
+Tax	B-GENE
+-	O
+mediated	O
+trans	O
+-	O
+activation	O
+has	O
+been	O
+well	O
+investigated	O
+.	O
+
+METHODS	O
+:	O
+109	O
+suspected	O
+cases	O
+with	O
+SS	O
+underwent	O
+the	O
+biopsies	O
+.	O
+
+We	O
+also	O
+identify	O
+several	O
+regulatory	O
+domain	O
+mutants	O
+in	O
+which	O
+Cd	O
+(	O
+2	O
++	O
+)	O
+tolerance	O
+of	O
+the	O
+mutant	O
+strain	O
+and	O
+transport	O
+activity	O
+of	O
+the	O
+protein	O
+are	O
+dissociated	O
+.	O
+
+The	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+-	I-GENE
+1	I-GENE
+(	I-GENE
+HIV	I-GENE
+-	I-GENE
+1	I-GENE
+)	I-GENE
+Tat	I-GENE
+protein	I-GENE
+regulates	O
+transcription	O
+by	O
+stimulating	O
+RNA	B-GENE
+polymerase	I-GENE
+processivity	O
+.	O
+
+One	O
+of	O
+these	O
+SEBPs	B-GENE
+,	O
+SEBP2	B-GENE
+,	O
+was	O
+shown	O
+to	O
+be	O
+the	O
+product	O
+of	O
+the	O
+homeotic	B-GENE
+gene	I-GENE
+fork	B-GENE
+head	I-GENE
+.	O
+
+Identity	O
+elements	O
+in	O
+tRNA	O
+for	O
+mono	O
+-	O
+and	O
+dimethylation	O
+reactions	O
+by	O
+the	O
+recombinant	B-GENE
+pfTrm1p	I-GENE
+were	O
+identified	O
+using	O
+in	O
+vitro	O
+T7	O
+transcripts	O
+of	O
+33	O
+variants	O
+of	O
+tRNA	B-GENE
+(	I-GENE
+Asp	I-GENE
+)	I-GENE
+and	O
+tRNA	B-GENE
+(	I-GENE
+Phe	I-GENE
+)	I-GENE
+from	O
+yeast	O
+.	O
+
+In	O
+insulin	B-GENE
+-	O
+responsive	O
+cells	O
+,	O
+Akt	B-GENE
+phosphorylates	O
+and	O
+inactivates	O
+the	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+glycogen	B-GENE
+synthase	I-GENE
+kinase	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+GSK	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+.	O
+
+The	O
+B	B-GENE
+cell	I-GENE
+antigen	I-GENE
+receptor	I-GENE
+activates	O
+the	O
+Akt	B-GENE
+(	O
+protein	B-GENE
+kinase	I-GENE
+B	I-GENE
+)	O
+/	O
+glycogen	B-GENE
+synthase	I-GENE
+kinase	I-GENE
+-	I-GENE
+3	I-GENE
+signaling	O
+pathway	O
+via	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+.	O
+
+Fewer	O
+recombination	O
+events	O
+are	O
+detected	O
+in	O
+four	O
+different	O
+B	O
+and	O
+T	O
+cell	O
+lines	O
+that	O
+do	O
+not	O
+undergo	O
+switch	O
+recombination	O
+of	O
+their	O
+endogenous	O
+genes	O
+.	O
+
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+TNF	B-GENE
+increase	O
+AND	B-GENE
+-	I-GENE
+34	I-GENE
+transcript	I-GENE
+levels	O
+in	O
+thymic	O
+cortical	O
+reticular	O
+,	O
+thymic	O
+nurse	O
+,	O
+and	O
+fibroblast	O
+cell	O
+lines	O
+.	O
+
+To	O
+determine	O
+what	O
+role	O
+eIF4E	B-GENE
+might	O
+play	O
+in	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+expression	O
+,	O
+the	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+5	I-GENE
+'	I-GENE
+untranslated	I-GENE
+region	I-GENE
+(	I-GENE
+UTR	I-GENE
+)	I-GENE
+was	O
+fused	O
+in	O
+-	O
+frame	O
+to	O
+CAT	B-GENE
+reporters	I-GENE
+,	O
+and	O
+several	O
+more	O
+derivative	O
+constructs	O
+were	O
+made	O
+.	O
+
+Analysis	O
+of	O
+cell	O
+cycle	O
+proteins	O
+showed	O
+that	O
+24	O
+h	O
+of	O
+lovastatin	O
+treatment	O
+in	O
+the	O
+control	O
+cells	O
+caused	O
+an	O
+elevation	O
+in	O
+the	O
+levels	O
+of	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+inhibitor	O
+p27	B-GENE
+(	O
+kip1	B-GENE
+)	O
+,	O
+inhibition	O
+of	O
+both	O
+cyclin	B-GENE
+E	I-GENE
+-	I-GENE
+and	I-GENE
+cyclin	I-GENE
+A	I-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+activity	O
+,	O
+and	O
+decreased	O
+levels	O
+of	O
+hyperphosphorylated	O
+retinoblastoma	B-GENE
+protein	I-GENE
+(	O
+pRb	B-GENE
+)	O
+.	O
+
+RESULTS	O
+:	O
+Circulating	O
+leptin	B-GENE
+concentrations	O
+in	O
+AN	O
+were	O
+3	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+versus	O
+7	O
+.	O
+6	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+ng	O
+/	O
+ml	O
+in	O
+control	O
+subjects	O
+.	O
+
+Copyright	O
+1999	O
+Academic	O
+Press	O
+.	O
+
+Oligonucleotide	O
+probes	O
+corresponding	O
+to	O
+wild	O
+-	O
+type	O
+and	O
+mutant	O
+EpRE	O
+sequences	O
+were	O
+used	O
+in	O
+gel	O
+-	O
+shift	O
+and	O
+super	O
+-	O
+shift	O
+analyses	O
+to	O
+identify	O
+proteins	O
+binding	O
+.	O
+
+PKNbeta	B-GENE
+had	O
+high	O
+sequence	O
+homology	O
+with	O
+PKNalpha	B-GENE
+,	O
+originally	O
+isolated	O
+PKN	B-GENE
+,	O
+especially	O
+in	O
+the	O
+repeats	O
+of	O
+charged	O
+amino	O
+acid	O
+-	O
+rich	O
+region	O
+with	O
+leucine	O
+-	O
+zipper	O
+like	O
+sequences	O
+(	O
+CZ	O
+region	O
+/	O
+HR1	O
+)	O
+,	O
+in	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+catalytic	O
+domain	O
+,	O
+and	O
+in	O
+approximately	O
+130	O
+amino	O
+acid	O
+stretch	O
+(	O
+D	O
+region	O
+/	O
+HR2	O
+)	O
+,	O
+located	O
+between	O
+CZ	O
+region	O
+/	O
+HR1	O
+and	O
+the	O
+catalytic	O
+domain	O
+.	O
+
+At	O
+baseline	O
+,	O
+serum	O
+levels	O
+of	O
+lycopene	O
+and	O
+FLOP	O
+were	O
+abnormally	O
+high	O
+and	O
+serum	O
+FLOP	O
+was	O
+correlated	O
+significantly	O
+with	O
+plasma	O
+cyclosporine	O
+levels	O
+(	O
+r	O
+=	O
+0	O
+.	O
+646	O
+,	O
+p	O
+=	O
+0	O
+.	O
+016	O
+)	O
+.	O
+
+BACKGROUND	O
+:	O
+Chronic	O
+alcohol	O
+consumption	O
+has	O
+been	O
+demonstrated	O
+to	O
+be	O
+deleterious	O
+to	O
+bone	O
+health	O
+.	O
+
+Interestingly	O
+,	O
+following	O
+induction	O
+of	O
+stress	O
+by	O
+heat	O
+shock	O
+,	O
+high	O
+salt	O
+,	O
+or	O
+ethanol	O
+,	O
+conditions	O
+under	O
+which	O
+most	O
+mRNA	O
+export	O
+is	O
+blocked	O
+,	O
+Npl3p	B-GENE
+is	O
+still	O
+exported	O
+from	O
+the	O
+nucleus	O
+.	O
+
+For	O
+symptomatic	O
+relief	O
+and	O
+inhibition	O
+of	O
+the	O
+growth	O
+of	O
+the	O
+metastases	O
+interferon	B-GENE
+-	I-GENE
+a	I-GENE
+and	O
+somatostatin	B-GENE
+analogues	O
+can	O
+be	O
+employed	O
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+no	O
+-	O
+adverse	O
+-	O
+effect	O
+-	O
+level	O
+for	O
+this	O
+study	O
+was	O
+determined	O
+to	O
+be	O
+1000	O
+ppm	O
+,	O
+based	O
+on	O
+decreased	O
+weight	O
+gain	O
+in	O
+female	O
+rats	O
+,	O
+and	O
+on	O
+slight	O
+organ	O
+weight	O
+changes	O
+in	O
+both	O
+sexes	O
+at	O
+3000	O
+ppm	O
+.	O
+
+Some	O
+of	O
+them	O
+produce	O
+gigantic	O
+sperm	O
+several	O
+times	O
+the	O
+total	O
+male	O
+body	O
+length	O
+.	O
+
+PDGF	B-GENE
+A	I-GENE
+-	I-GENE
+chain	I-GENE
+levels	O
+increase	O
+in	O
+cultured	O
+vascular	O
+smooth	O
+muscle	O
+cells	O
+(	O
+SMCs	O
+)	O
+exposed	O
+to	O
+ATII	B-GENE
+.	O
+
+M	B-GENE
+-	I-GENE
+Ras	I-GENE
+interacted	O
+poorly	O
+in	O
+a	O
+yeast	O
+two	O
+-	O
+hybrid	O
+assay	O
+with	O
+multiple	O
+Ras	B-GENE
+effectors	O
+,	O
+including	O
+c	B-GENE
+-	I-GENE
+Raf	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+A	B-GENE
+-	I-GENE
+Raf	I-GENE
+,	O
+B	B-GENE
+-	I-GENE
+Raf	I-GENE
+,	O
+phosphoinositol	B-GENE
+-	I-GENE
+3	I-GENE
+kinase	I-GENE
+delta	I-GENE
+,	O
+RalGDS	B-GENE
+,	O
+and	O
+Rin1	B-GENE
+.	O
+
+Deletion	O
+mapping	O
+of	O
+the	O
+human	B-GENE
+presenilin	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+PS1	B-GENE
+)	O
+promoter	O
+delineated	O
+the	O
+most	O
+active	O
+fragment	O
+from	O
+-	O
+118	O
+to	O
++	O
+178	O
+in	O
+relation	O
+to	O
+the	O
+transcription	O
+start	O
+site	O
+mapped	O
+in	O
+this	O
+study	O
+,	O
+in	O
+both	O
+human	O
+neuroblastoma	O
+SK	O
+-	O
+N	O
+-	O
+SH	O
+and	O
+hepatoma	O
+HepG2	O
+cells	O
+.	O
+
+Analysis	O
+of	O
+the	O
+E2F1	B-GENE
+gene	I-GENE
+promoter	I-GENE
+showed	O
+that	O
+the	O
+-	O
+146	O
+to	O
+-	O
+54	O
+region	O
+was	O
+required	O
+for	O
+E2	B-GENE
+-	O
+responsiveness	O
+in	O
+transient	O
+transfection	O
+assays	O
+,	O
+and	O
+subsequent	O
+deletion	O
+/	O
+mutation	O
+analysis	O
+showed	O
+that	O
+a	O
+single	O
+upstream	O
+GC	O
+-	O
+rich	O
+and	O
+two	O
+downstream	O
+CCAAT	O
+-	O
+binding	O
+sites	O
+were	O
+required	O
+for	O
+transactivation	O
+by	O
+E2	B-GENE
+.	O
+
+In	O
+the	O
+course	O
+of	O
+investigating	O
+the	O
+mechanisms	O
+by	O
+which	O
+OF5	B-GENE
+and	O
+OF3	B-GENE
+regulated	O
+CYP11A1	B-GENE
+transcription	O
+,	O
+we	O
+found	O
+that	O
+OF5	B-GENE
+and	O
+OF3	B-GENE
+bound	O
+Sp1	B-GENE
+and	O
+Sp3	B-GENE
+in	O
+JEG	O
+-	O
+3	O
+cells	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+differentiation	O
+of	O
+neoplastically	O
+transformed	O
+cells	O
+does	O
+not	O
+repress	O
+mitogenic	O
+responsiveness	O
+or	O
+junB	B-GENE
+or	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+inducibility	O
+.	O
+
+Adipocyte	O
+differentiation	O
+of	O
+nontransformed	O
+cells	O
+also	O
+markedly	O
+represses	O
+the	O
+ability	O
+of	O
+SRF	B-GENE
+to	O
+bind	O
+to	O
+the	O
+junB	B-GENE
+SRE	O
+,	O
+the	O
+c	B-GENE
+-	I-GENE
+fos	I-GENE
+SRE	O
+,	O
+and	O
+other	O
+SREs	O
+,	O
+as	O
+determined	O
+by	O
+mobility	O
+shift	O
+and	O
+gel	O
+supershift	O
+assays	O
+,	O
+without	O
+affecting	O
+the	O
+DNA	O
+binding	O
+characteristics	O
+of	O
+the	O
+nuclear	O
+protein	O
+SP	O
+-	O
+1	O
+.	O
+
+Transformation	O
+blocks	O
+differentiation	O
+-	O
+induced	O
+inhibition	O
+of	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+interactions	O
+with	O
+serum	O
+response	O
+elements	O
+.	O
+
+The	O
+core	B-GENE
+enzyme	I-GENE
+is	O
+homologous	O
+to	O
+those	O
+of	O
+bacteriophages	O
+T3	O
+,	O
+T7	O
+and	O
+SP6	O
+whereas	O
+the	O
+specificity	O
+factor	O
+shows	O
+similarities	O
+with	O
+bacterial	B-GENE
+sigma	I-GENE
+factors	I-GENE
+.	O
+
+The	O
+Cr	B-GENE
+.	I-GENE
+psbA	I-GENE
+-	I-GENE
+4	I-GENE
+ORF	I-GENE
+contains	O
+an	O
+H	O
+-	O
+N	O
+-	O
+H	O
+motif	O
+,	O
+and	O
+possibly	O
+a	O
+GIY	O
+-	O
+YIG	O
+motif	O
+.	O
+
+The	O
+interaction	O
+of	O
+zf4	B-GENE
+-	I-GENE
+6	I-GENE
+with	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+5	I-GENE
+S	I-GENE
+RNA	I-GENE
+was	O
+far	O
+more	O
+sensitive	O
+to	O
+non	O
+-	O
+specific	O
+competitor	O
+concentration	O
+than	O
+was	O
+the	O
+zf4	B-GENE
+-	I-GENE
+7	I-GENE
+:	O
+5	B-GENE
+S	I-GENE
+RNA	I-GENE
+interaction	O
+,	O
+suggesting	O
+that	O
+finger	O
+seven	O
+contributes	O
+to	O
+both	O
+affinity	O
+and	O
+specificity	O
+in	O
+this	O
+protein	O
+:	O
+RNA	O
+interaction	O
+.	O
+
+The	O
+STAT	B-GENE
+protein	I-GENE
+accumulation	O
+resulting	O
+from	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+expression	O
+was	O
+tightly	O
+coupled	O
+to	O
+the	O
+morphological	O
+conversion	O
+of	O
+fibroblasts	O
+to	O
+adipocytes	O
+and	O
+represents	O
+an	O
+expression	O
+profile	O
+identical	O
+to	O
+that	O
+reported	O
+for	O
+mature	O
+adipocytes	O
+in	O
+vivo	O
+.	O
+
+The	O
+median	O
+durations	O
+for	O
+response	O
+and	O
+survival	O
+time	O
+in	O
+the	O
+late	O
+phase	O
+II	O
+trial	O
+were	O
+2	O
+.	O
+3	O
+months	O
+and	O
+5	O
+.	O
+8	O
+months	O
+,	O
+respectively	O
+.	O
+
+The	O
+role	O
+of	O
+'	O
+scientific	O
+psychiatry	O
+'	O
+in	O
+understanding	O
+patients	O
+with	O
+chronic	O
+schizophrenia	O
+or	O
+severe	O
+personality	O
+disorder	O
+.	O
+
+Myocardial	O
+antioxidant	O
+enzymes	O
+,	O
+catalase	B-GENE
+,	O
+glutathione	B-GENE
+peroxidase	I-GENE
+and	O
+superoxide	B-GENE
+dismutase	I-GENE
+,	O
+in	O
+the	O
+MCT	O
+-	O
+treated	O
+rats	O
+were	O
+not	O
+different	O
+compared	O
+to	O
+control	O
+rats	O
+.	O
+
+The	O
+second	O
+goal	O
+was	O
+to	O
+ascertain	O
+the	O
+somatotopic	O
+arrangement	O
+of	O
+the	O
+GPi	O
+in	O
+PD	O
+.	O
+
+These	O
+overall	O
+results	O
+indicate	O
+that	O
+there	O
+is	O
+generally	O
+one	O
+PERV	O
+copy	O
+per	O
+integration	O
+site	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+determine	O
+whether	O
+administration	O
+of	O
+misoprostol	O
+prevents	O
+gastric	O
+hemorrhage	O
+in	O
+healthy	O
+dogs	O
+treated	O
+with	O
+high	O
+doses	O
+of	O
+methylprednisolone	O
+sodium	O
+succinate	O
+(	O
+MPSS	O
+)	O
+.	O
+
+Patients	O
+were	O
+assessed	O
+for	O
+cardiac	O
+MIBG	O
+uptake	O
+,	O
+circulating	O
+norepinephrine	O
+concentration	O
+,	O
+LVEF	O
+,	O
+peak	O
+Vo2	O
+,	O
+x	O
+-	O
+ray	O
+cardiothoracic	O
+ratio	O
+,	O
+M	O
+-	O
+mode	O
+echographic	O
+end	O
+-	O
+diastolic	O
+diameter	O
+and	O
+right	O
+-	O
+sided	O
+heart	O
+catheterization	O
+parameters	O
+.	O
+
+Nuclear	O
+hormone	O
+receptors	O
+(	O
+NRs	O
+)	O
+are	O
+ligand	O
+-	O
+inducible	O
+transcription	O
+factors	O
+that	O
+mediate	O
+critical	O
+functions	O
+in	O
+many	O
+species	O
+.	O
+
+These	O
+cells	O
+were	O
+able	O
+to	O
+present	O
+influenza	O
+virus	O
+particles	O
+to	O
+HLA	B-GENE
+-	I-GENE
+DR1	I-GENE
+-	O
+restricted	O
+T	O
+cell	O
+clones	O
+.	O
+
+Sequencing	O
+of	O
+zebrafish	O
+(	O
+Danio	O
+rerio	O
+)	O
+bacterial	O
+artificial	O
+chromosome	O
+and	O
+P1	O
+artificial	O
+chromosome	O
+genomic	O
+clone	O
+fragments	O
+and	O
+of	O
+cDNA	O
+clones	O
+has	O
+led	O
+to	O
+the	O
+identification	O
+of	O
+five	O
+new	O
+loci	O
+coding	O
+for	O
+beta	O
+subunits	O
+of	O
+proteasomes	O
+(	O
+PSMB	B-GENE
+)	O
+.	O
+
+In	O
+addition	O
+to	O
+homologues	O
+of	O
+the	O
+human	B-GENE
+genes	I-GENE
+PSMB5	I-GENE
+through	O
+PSMB9	B-GENE
+,	O
+two	O
+new	O
+genes	O
+,	O
+PSMB11	B-GENE
+and	O
+PSMB12	B-GENE
+,	O
+have	O
+been	O
+found	O
+for	O
+which	O
+there	O
+are	O
+no	O
+known	O
+corresponding	O
+genes	O
+in	O
+humans	O
+.	O
+
+It	O
+applies	O
+Udry	O
+'	O
+s	O
+biosocial	O
+perspective	O
+,	O
+which	O
+attempts	O
+to	O
+reconcile	O
+the	O
+biological	O
+and	O
+sociological	O
+models	O
+of	O
+premarital	O
+sexual	O
+and	O
+reproductive	O
+behaviour	O
+.	O
+
+Weight	O
+and	O
+height	O
+z	O
+-	O
+scores	O
+were	O
+significantly	O
+associated	O
+with	O
+BMD	O
+z	O
+-	O
+scores	O
+.	O
+
+A	O
+limited	O
+sampling	O
+strategy	O
+was	O
+used	O
+based	O
+on	O
+a	O
+bayesian	O
+parameter	O
+estimation	O
+algorithm	O
+that	O
+is	O
+part	O
+of	O
+the	O
+ADAPT	O
+II	O
+software	O
+package	O
+.	O
+
+The	O
+amino	O
+acid	O
+changes	O
+D206A	O
+and	O
+D208A	O
+abolish	O
+singly	O
+or	O
+in	O
+combination	O
+the	O
+exonuclease	O
+activity	O
+in	O
+vivo	O
+.	O
+
+Previous	O
+experimental	O
+evidence	O
+had	O
+indicated	O
+that	O
+Reg1	B-GENE
+might	O
+target	O
+Glc7	B-GENE
+to	O
+nuclear	O
+substrates	O
+such	O
+as	O
+the	O
+Snf1	B-GENE
+kinase	I-GENE
+complex	I-GENE
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+demonstrate	O
+that	O
+expression	O
+of	O
+TD	B-GENE
+-	I-GENE
+IkappaBalpha	I-GENE
+blocked	O
+phorbol	O
+myristate	O
+acetate	B-GENE
+-	I-GENE
+phytohemagglutinin	I-GENE
+or	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+-	O
+induced	O
+IkappaBalpha	B-GENE
+gene	I-GENE
+transcription	O
+and	O
+abolished	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+DNA	O
+binding	O
+activity	O
+,	O
+due	O
+to	O
+the	O
+continued	O
+cytoplasmic	O
+sequestration	O
+of	O
+RelA	B-GENE
+(	O
+p65	B-GENE
+)	O
+by	O
+TD	B-GENE
+-	I-GENE
+IkappaBalpha	I-GENE
+.	O
+
+(	O
+i	O
+)	O
+Complete	O
+Grb10	B-GENE
+expression	O
+from	O
+cDNA	O
+with	O
+an	O
+ecdysone	O
+-	O
+regulated	O
+transient	O
+expression	O
+system	O
+stimulated	O
+PDGF	B-GENE
+-	I-GENE
+BB	I-GENE
+-	O
+,	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+,	O
+and	O
+insulin	B-GENE
+-	O
+but	O
+not	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+EGF	B-GENE
+)	O
+-	O
+induced	O
+DNA	O
+synthesis	O
+in	O
+an	O
+ecdysone	O
+dose	O
+-	O
+responsive	O
+fashion	O
+.	O
+
+The	O
+analysis	O
+of	O
+two	O
+distinct	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+pathways	O
+shows	O
+that	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+-	O
+Jun	B-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+activation	O
+,	O
+resulting	O
+in	O
+the	O
+phosphorylation	O
+of	O
+ATF	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+,	O
+and	O
+JunD	B-GENE
+,	O
+is	O
+required	O
+not	O
+only	O
+for	O
+the	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+but	O
+also	O
+for	O
+the	O
+TPA	O
+-	O
+dependent	O
+induction	O
+,	O
+while	O
+the	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+related	I-GENE
+kinase	I-GENE
+1	I-GENE
+(	O
+ERK	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+ERK	B-GENE
+-	I-GENE
+2	I-GENE
+activation	O
+is	O
+involved	O
+in	O
+the	O
+TPA	O
+-	O
+but	O
+not	O
+in	O
+the	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+dependent	O
+stimulation	O
+of	O
+the	O
+uPA	B-GENE
+enhancer	I-GENE
+.	O
+
+CONCLUSIONS	O
+:	O
+In	O
+healthy	O
+individuals	O
+,	O
+whole	O
+body	O
+insulin	B-GENE
+sensitivity	O
+is	O
+related	O
+,	O
+or	O
+"	O
+coupled	O
+,	O
+"	O
+to	O
+the	O
+anaerobic	O
+threshold	O
+.	O
+
+Interdomain	O
+signaling	O
+in	O
+a	O
+two	O
+-	O
+domain	O
+fragment	O
+of	O
+the	O
+human	B-GENE
+glucocorticoid	I-GENE
+receptor	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+xtRNA	B-GENE
+(	O
+Sec	B-GENE
+)	O
+gene	O
+needs	O
+the	O
+binding	O
+of	O
+the	O
+seven	O
+Staf	B-GENE
+zinc	I-GENE
+fingers	I-GENE
+,	O
+but	O
+not	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+for	O
+optimal	O
+transcriptional	O
+capacity	O
+.	O
+
+Collectively	O
+,	O
+these	O
+results	O
+show	O
+that	O
+the	O
+differential	O
+utilization	O
+of	O
+Staf	B-GENE
+zinc	I-GENE
+finger	I-GENE
+1	I-GENE
+represents	O
+a	O
+new	O
+,	O
+critical	O
+determinant	O
+of	O
+the	O
+transcriptional	O
+activation	O
+mechanism	O
+for	O
+the	O
+Xenopus	B-GENE
+tRNA	I-GENE
+(	O
+Sec	B-GENE
+)	O
+and	O
+human	B-GENE
+U6	I-GENE
+snRNA	I-GENE
+genes	I-GENE
+.	O
+
+In	O
+B	O
+cells	O
+,	O
+HEF1	B-GENE
+is	O
+phosphorylated	O
+by	O
+a	O
+cytoskeleton	O
+-	O
+dependent	O
+mechanism	O
+that	O
+is	O
+triggered	O
+by	O
+integrin	B-GENE
+ligation	O
+.	O
+
+The	O
+calcitonin	B-GENE
+-	O
+induced	O
+tyrosine	O
+phosphorylation	O
+of	O
+HEF1	B-GENE
+increased	O
+in	O
+a	O
+time	O
+-	O
+and	O
+dose	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Independent	O
+protrudor	O
+muscle	O
+stimulation	O
+increased	O
+VI	O
+,	O
+max	O
+(	O
+peak	O
+increase	O
+61	O
+%	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+did	O
+not	O
+change	O
+Pcrit	O
+,	O
+and	O
+decreased	O
+Rn	O
+(	O
+peak	O
+decrease	O
+of	O
+41	O
+%	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+human	B-GENE
+RAD30B	I-GENE
+and	O
+mouse	B-GENE
+Rad30b	I-GENE
+mRNA	I-GENE
+transcripts	I-GENE
+,	O
+like	O
+many	O
+repair	O
+proteins	O
+,	O
+are	O
+highly	O
+expressed	O
+in	O
+the	O
+testis	O
+.	O
+
+Analysis	O
+of	O
+the	O
+mouse	B-GENE
+STAP	I-GENE
+gene	I-GENE
+isolated	O
+from	O
+the	O
+genomic	O
+library	O
+revealed	O
+that	O
+the	O
+STAP	B-GENE
+gene	I-GENE
+spans	O
+a	O
+region	O
+of	O
+over	O
+11	O
+kb	O
+and	O
+comprises	O
+eight	O
+exons	O
+.	O
+
+A	O
+reduced	O
+matrix	O
+distribution	O
+and	O
+enhanced	O
+cell	O
+density	O
+were	O
+observed	O
+as	O
+the	O
+biofilm	O
+aged	O
+.	O
+
+After	O
+10	O
+months	O
+of	O
+treatment	O
+with	O
+the	O
+conjugated	O
+estrogen	O
+,	O
+both	O
+his	O
+height	O
+and	O
+weight	O
+showed	O
+improvement	O
+,	O
+while	O
+his	O
+bone	O
+mineral	O
+density	O
+and	O
+bone	O
+age	O
+were	O
+increased	O
+.	O
+
+Viscosity	O
+experiments	O
+on	O
+the	O
+catalytic	O
+fragment	O
+kinase	O
+reaction	O
+demonstrated	O
+that	O
+the	O
+chemical	O
+(	O
+phosphoryl	O
+transfer	O
+)	O
+step	O
+had	O
+a	O
+reduced	O
+rate	O
+.	O
+
+Velocity	O
+sedimentation	O
+,	O
+cross	O
+-	O
+linking	O
+,	O
+and	O
+immunoprecipitation	O
+analyses	O
+of	O
+detergent	O
+-	O
+solubilized	O
+rat	O
+brain	O
+revealed	O
+that	O
+the	O
+32	O
+and	O
+34	O
+kDa	O
+polypeptides	O
+reside	O
+within	O
+heterotetramers	O
+.	O
+
+In	O
+vitro	O
+expression	O
+levels	O
+of	O
+the	O
+different	O
+plasmids	O
+differed	O
+by	O
+as	O
+much	O
+as	O
+tenfold	O
+.	O
+
+In	O
+EEG	O
+only	O
+single	O
+slow	O
+waves	O
+above	O
+left	O
+temporal	O
+region	O
+were	O
+revealed	O
+.	O
+
+Molecular	O
+characterization	O
+of	O
+type	O
+-	O
+specific	O
+capsular	O
+polysaccharide	O
+biosynthesis	O
+genes	O
+of	O
+Streptococcus	O
+agalactiae	O
+type	O
+Ia	O
+.	O
+
+(	O
+1998	O
+)	O
+FASEB	O
+J	O
+.	O
+
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+(	O
+10	O
+ng	O
+/	O
+ml	O
+)	O
+drastically	O
+increased	O
+both	O
+PDGFalphaR	B-GENE
+and	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+delta	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBPdelta	I-GENE
+)	O
+mRNA	O
+levels	O
+in	O
+a	O
+time	O
+dependent	O
+manner	O
+.	O
+
+Transient	O
+tyrosine	O
+phosphorylation	O
+of	O
+Crk	B-GENE
+in	O
+fibroblast	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+2	I-GENE
+-	O
+stimulated	O
+endothelial	O
+cells	O
+was	O
+dependent	O
+on	O
+the	O
+juxtamembrane	O
+tyrosine	O
+residue	O
+463	O
+in	O
+FGFR	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+and	O
+a	O
+Crk	B-GENE
+SH2	B-GENE
+domain	I-GENE
+precipitated	O
+FGFR	B-GENE
+-	I-GENE
+1	I-GENE
+via	O
+phosphorylated	O
+Tyr	O
+-	O
+463	O
+,	O
+indicating	O
+direct	O
+complex	O
+formation	O
+between	O
+Crk	B-GENE
+and	O
+FGFR	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Role	O
+of	O
+the	O
+3	O
+'	O
+untranslated	O
+region	O
+of	O
+baculovirus	B-GENE
+p10	I-GENE
+mRNA	I-GENE
+in	O
+high	O
+-	O
+level	O
+expression	O
+of	O
+foreign	O
+genes	O
+.	O
+
+The	O
+intron	O
+RNA	O
+consists	O
+of	O
+2492	O
+nucleotides	O
+which	O
+can	O
+be	O
+folded	O
+into	O
+a	O
+secondary	O
+structure	O
+with	O
+all	O
+the	O
+expected	O
+sequence	O
+motifs	O
+of	O
+subgroup	O
+-	O
+IIA1	O
+introns	O
+(	O
+Michel	O
+et	O
+al	O
+.	O
+
+The	O
+intron	O
+is	O
+capable	O
+of	O
+splicing	O
+despite	O
+the	O
+fact	O
+that	O
+both	O
+the	O
+EBS1	B-GENE
+/	O
+IBS1	B-GENE
+and	O
+the	O
+EBS2	B-GENE
+/	O
+IBS2	B-GENE
+sequence	O
+motifs	O
+,	O
+thought	O
+to	O
+be	O
+necessary	O
+for	O
+correct	O
+splicing	O
+,	O
+extend	O
+over	O
+5	O
+instead	O
+of	O
+6	O
+bp	O
+.	O
+
+The	O
+Trk	B-GENE
+/	I-GENE
+Nerve	I-GENE
+Growth	I-GENE
+Factor	I-GENE
+receptor	I-GENE
+mediates	O
+the	O
+rapid	O
+activation	O
+of	O
+a	O
+number	O
+of	O
+intracellular	O
+signaling	O
+proteins	O
+,	O
+including	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+(	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+)	O
+.	O
+
+Chemical	O
+uptake	O
+into	O
+human	O
+stratum	O
+corneum	O
+in	O
+vivo	O
+from	O
+volatile	O
+and	O
+non	O
+-	O
+volatile	O
+solvents	O
+.	O
+
+Like	O
+DNA	O
+binding	O
+,	O
+transcriptional	O
+enhancement	O
+required	O
+amino	O
+-	O
+terminally	O
+located	O
+basic	O
+amino	O
+acid	O
+residues	O
+but	O
+not	O
+the	O
+carboxyl	O
+-	O
+terminal	O
+portion	O
+of	O
+Hap46	B-GENE
+known	O
+to	O
+participate	O
+in	O
+hsp70	B-GENE
+interaction	O
+.	O
+
+We	O
+have	O
+tested	O
+the	O
+function	O
+of	O
+two	O
+potential	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+-	I-GENE
+like	I-GENE
+sites	I-GENE
+present	O
+in	O
+the	O
+PAI	B-GENE
+-	I-GENE
+2	I-GENE
+proximal	I-GENE
+promoter	I-GENE
+for	O
+responsiveness	O
+to	O
+TNFalpha	B-GENE
+using	O
+chloramphenicol	B-GENE
+acetyl	I-GENE
+transferase	I-GENE
+reporter	I-GENE
+gene	I-GENE
+deletion	O
+and	O
+mutation	O
+analyses	O
+.	O
+
+N	O
+-	O
+terminal	O
+sequence	O
+analysis	O
+and	O
+NMR	O
+measurements	O
+revealed	O
+that	O
+this	O
+fragment	O
+originates	O
+from	O
+the	O
+C	O
+-	O
+terminal	O
+80	O
+residues	O
+of	O
+MBF1	B-GENE
+and	O
+form	O
+a	O
+well	O
+structured	O
+C	O
+-	O
+terminal	O
+domain	O
+of	O
+MBF1	B-GENE
+,	O
+MBF1CTD	B-GENE
+.	O
+
+The	O
+nucleosomal	O
+response	O
+associated	O
+with	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+gene	I-GENE
+induction	O
+is	O
+mediated	O
+via	O
+alternative	O
+MAP	B-GENE
+kinase	I-GENE
+cascades	I-GENE
+:	O
+MSK1	B-GENE
+as	O
+a	O
+potential	O
+histone	B-GENE
+H3	I-GENE
+/	O
+HMG	B-GENE
+-	I-GENE
+14	I-GENE
+kinase	O
+.	O
+
+272	O
+,	O
+1904	O
+]	O
+.	O
+
+Using	O
+16	O
+strains	O
+of	O
+C	O
+.	O
+trachomatis	O
+in	O
+triplicate	O
+assays	O
+,	O
+we	O
+found	O
+the	O
+RT	O
+-	O
+PCR	O
+method	O
+consistently	O
+more	O
+sensitive	O
+than	O
+the	O
+conventional	O
+technique	O
+for	O
+all	O
+eight	O
+antimicrobials	O
+tested	O
+,	O
+with	O
+resultant	O
+MICs	O
+determined	O
+by	O
+RT	O
+-	O
+PCR	O
+ranging	O
+from	O
+1	O
+.	O
+6	O
+-	O
+fold	O
+higher	O
+(	O
+erythromycin	O
+)	O
+to	O
+>	O
+/	O
+=	O
+195	O
+-	O
+fold	O
+higher	O
+(	O
+amoxicillin	O
+)	O
+.	O
+
+Recent	O
+molecular	O
+analysis	O
+has	O
+revealed	O
+that	O
+the	O
+S	B-GENE
+locus	I-GENE
+is	O
+highly	O
+polymorphic	O
+and	O
+contains	O
+several	O
+genes	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+SLG	B-GENE
+,	O
+SRK	B-GENE
+,	O
+the	O
+as	O
+-	O
+yet	O
+-	O
+unidentified	O
+pollen	B-GENE
+S	I-GENE
+gene	I-GENE
+(	I-GENE
+s	I-GENE
+)	I-GENE
+,	O
+and	O
+other	O
+linked	O
+genes	O
+.	O
+
+A	O
+cDNA	O
+encoding	O
+a	O
+putative	O
+RNA	B-GENE
+and	I-GENE
+/	I-GENE
+or	I-GENE
+DNA	I-GENE
+helicase	I-GENE
+has	O
+been	O
+isolated	O
+from	O
+Arabidopsis	O
+thaliana	O
+cDNA	O
+libraries	O
+.	O
+
+In	O
+vivo	O
+,	O
+MyoD	B-GENE
+requires	O
+this	O
+tryptophan	O
+motif	O
+to	O
+evoke	O
+chromatin	O
+remodeling	O
+in	O
+the	O
+Myogenin	B-GENE
+promoter	I-GENE
+and	O
+to	O
+activate	O
+Myogenin	B-GENE
+transcription	O
+.	O
+
+Feed	O
+intake	O
+and	O
+BW	O
+gains	O
+were	O
+decreased	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+by	O
+dietary	O
+treatments	O
+containing	O
+M	O
+.	O
+
+The	O
+N	O
+terminus	O
+of	O
+beta	O
+(	O
+95	O
+kDa	O
+)	O
+corresponds	O
+to	O
+alpha	O
+with	O
+the	O
+integrase	B-GENE
+domain	I-GENE
+attached	O
+to	O
+the	O
+C	O
+terminus	O
+(	O
+32	O
+kDa	O
+)	O
+.	O
+
+Skn	B-GENE
+-	I-GENE
+1a	I-GENE
+lacking	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+completely	O
+lost	O
+transactivation	O
+ability	O
+,	O
+irrespective	O
+of	O
+the	O
+promoter	O
+tested	O
+,	O
+and	O
+was	O
+able	O
+to	O
+block	O
+transactivation	O
+by	O
+normal	O
+Skn	B-GENE
+-	I-GENE
+1a	I-GENE
+in	O
+competition	O
+assays	O
+.	O
+
+In	O
+early	O
+Xenopus	O
+embryos	O
+,	O
+the	O
+transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta	I-GENE
+member	O
+activin	B-GENE
+induces	O
+the	O
+gene	B-GENE
+Mix	I-GENE
+.	I-GENE
+2	I-GENE
+by	O
+stimulating	O
+the	O
+formation	O
+of	O
+a	O
+multiprotein	O
+complex	O
+,	O
+activin	B-GENE
+-	I-GENE
+responsive	I-GENE
+factor	I-GENE
+(	O
+ARF	B-GENE
+)	O
+.	O
+
+To	O
+further	O
+characterize	O
+the	O
+structure	O
+and	O
+evolutionary	O
+synthesis	O
+of	O
+the	O
+CMT1A	O
+-	O
+REP	O
+repeat	O
+,	O
+fluorescent	O
+in	O
+situ	O
+hybridization	O
+(	O
+FISH	O
+)	O
+analysis	O
+and	O
+heterologous	O
+PCR	O
+-	O
+based	O
+assays	O
+were	O
+carried	O
+out	O
+for	O
+a	O
+series	O
+of	O
+primates	O
+.	O
+
+Natl	O
+.	O
+
+In	O
+the	O
+face	O
+of	O
+the	O
+outbreak	O
+,	O
+there	O
+was	O
+a	O
+delay	O
+before	O
+vaccination	O
+was	O
+able	O
+to	O
+stop	O
+deaths	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+a	O
+novel	O
+isoform	O
+of	O
+Rapl	B-GENE
+GTPase	I-GENE
+-	I-GENE
+activating	I-GENE
+protein	I-GENE
+,	O
+called	O
+rap1GAPII	B-GENE
+,	O
+binds	O
+specifically	O
+to	O
+the	O
+alpha	O
+-	O
+subunits	O
+of	O
+the	O
+G	B-GENE
+(	I-GENE
+i	I-GENE
+)	I-GENE
+family	I-GENE
+of	O
+heterotrimeric	B-GENE
+G	I-GENE
+-	I-GENE
+proteins	I-GENE
+.	O
+
+The	O
+B	O
+-	O
+oligomer	O
+of	O
+pertussis	B-GENE
+toxin	I-GENE
+deactivates	O
+CC	B-GENE
+chemokine	I-GENE
+receptor	I-GENE
+5	I-GENE
+and	O
+blocks	O
+entry	O
+of	O
+M	O
+-	O
+tropic	O
+HIV	O
+-	O
+1	O
+strains	O
+.	O
+
+Cross	O
+-	O
+linking	O
+the	O
+B	B-GENE
+cell	I-GENE
+Ag	I-GENE
+receptor	I-GENE
+(	O
+BCR	B-GENE
+)	O
+to	O
+surface	B-GENE
+Fc	I-GENE
+receptors	I-GENE
+for	O
+IgG	B-GENE
+(	O
+Fc	B-GENE
+gamma	I-GENE
+R	I-GENE
+)	O
+inhibits	O
+G1	O
+-	O
+to	O
+-	O
+S	O
+progression	O
+;	O
+the	O
+mechanism	O
+by	O
+which	O
+this	O
+occurs	O
+is	O
+not	O
+completely	O
+known	O
+.	O
+
+Cross	O
+-	O
+linking	O
+the	O
+B	B-GENE
+cell	I-GENE
+Ag	I-GENE
+receptor	I-GENE
+(	O
+BCR	B-GENE
+)	O
+to	O
+surface	B-GENE
+Fc	I-GENE
+receptors	I-GENE
+for	O
+IgG	B-GENE
+(	O
+Fc	B-GENE
+gamma	I-GENE
+R	I-GENE
+)	O
+inhibits	O
+G1	O
+-	O
+to	O
+-	O
+S	O
+progression	O
+;	O
+the	O
+mechanism	O
+by	O
+which	O
+this	O
+occurs	O
+is	O
+not	O
+completely	O
+known	O
+.	O
+
+TRAF2	B-GENE
+is	O
+a	O
+potent	O
+activator	O
+of	O
+a	O
+95	B-GENE
+-	I-GENE
+kDa	I-GENE
+serine	I-GENE
+/	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+termed	O
+germinal	B-GENE
+center	I-GENE
+kinase	I-GENE
+related	I-GENE
+(	O
+GCKR	B-GENE
+,	O
+also	O
+referred	O
+to	O
+as	O
+KHS1	B-GENE
+)	O
+,	O
+which	O
+signals	O
+activation	O
+of	O
+the	O
+SAPK	B-GENE
+pathway	O
+.	O
+
+An	O
+activation	O
+-	O
+responsive	O
+element	O
+in	O
+single	B-GENE
+C	I-GENE
+motif	I-GENE
+-	I-GENE
+1	I-GENE
+/	O
+lymphotactin	B-GENE
+promoter	O
+is	O
+a	O
+site	O
+of	O
+constitutive	O
+and	O
+inducible	O
+DNA	O
+-	O
+protein	O
+interactions	O
+involving	O
+nuclear	O
+factor	O
+of	O
+activated	O
+T	O
+cell	O
+.	O
+
+A	O
+portion	O
+of	O
+p193	B-GENE
+is	O
+nuclear	O
+and	O
+localizes	O
+to	O
+the	O
+mitotic	O
+spindle	O
+.	O
+
+The	O
+main	O
+issues	O
+are	O
+the	O
+need	O
+to	O
+explain	O
+a	O
+number	O
+of	O
+still	O
+unknown	O
+mechanisms	O
+,	O
+to	O
+determine	O
+which	O
+"	O
+natural	O
+diet	O
+"	O
+carries	O
+the	O
+minimum	O
+coronary	O
+risk	O
+and	O
+whether	O
+"	O
+new	O
+"	O
+foods	O
+produced	O
+by	O
+modern	O
+technology	O
+are	O
+really	O
+needed	O
+to	O
+contrast	O
+this	O
+epidemic	O
+.	O
+
+Cotransfection	O
+of	O
+the	O
+coactivator	O
+CREB	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+relieved	O
+the	O
+transcriptional	O
+repression	O
+of	O
+PPARalphawt	B-GENE
+by	O
+PPARalphatr	B-GENE
+,	O
+suggesting	O
+that	O
+the	O
+dominant	O
+negative	O
+effect	O
+of	O
+PPARalphatr	B-GENE
+might	O
+occur	O
+through	O
+competition	O
+for	O
+essential	O
+coactivators	O
+.	O
+
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+does	O
+not	O
+have	O
+an	O
+N	O
+-	O
+terminal	O
+AF1	O
+domain	O
+.	O
+
+We	O
+discuss	O
+these	O
+results	O
+in	O
+terms	O
+of	O
+the	O
+influence	O
+that	O
+time	O
+and	O
+nutritional	O
+constraints	O
+have	O
+on	O
+odonate	O
+development	O
+patterns	O
+and	O
+fitness	O
+.	O
+
+OBJECTIVE	O
+:	O
+1998	O
+Surveillance	O
+,	O
+Epidemiology	O
+,	O
+and	O
+End	O
+Results	O
+(	O
+SEER	O
+)	O
+data	O
+estimate	O
+an	O
+83	O
+.	O
+1	O
+%	O
+5	O
+-	O
+year	O
+survival	O
+rate	O
+for	O
+corpus	O
+uteri	O
+adenocarcinoma	O
+FIGO	O
+stage	O
+II	O
+.	O
+
+A	O
+novel	O
+Drosophila	B-GENE
+A	I-GENE
+kinase	I-GENE
+anchor	I-GENE
+protein	I-GENE
+,	O
+Drosophila	B-GENE
+A	I-GENE
+kinase	I-GENE
+anchor	I-GENE
+protein	I-GENE
+200	I-GENE
+(	O
+DAKAP200	B-GENE
+)	O
+,	O
+is	O
+predicted	O
+to	O
+be	O
+involved	O
+in	O
+routing	O
+,	O
+mediating	O
+,	O
+and	O
+integrating	O
+signals	O
+carried	O
+by	O
+cAMP	O
+,	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+,	O
+and	O
+diacylglycerol	O
+(	O
+Li	O
+,	O
+Z	O
+.	O
+,	O
+Rossi	O
+,	O
+E	O
+.	O
+
+In	O
+vitro	O
+transcription	O
+results	O
+indicate	O
+that	O
+this	O
+5	O
+'	O
+structure	O
+functions	O
+in	O
+the	O
+attenuation	O
+mechanism	O
+,	O
+since	O
+deletion	O
+of	O
+the	O
+stem	O
+-	O
+loop	O
+caused	O
+an	O
+increase	O
+in	O
+transcription	O
+readthrough	O
+.	O
+
+A	O
+5	O
+'	O
+RNA	O
+stem	O
+-	O
+loop	O
+participates	O
+in	O
+the	O
+transcription	O
+attenuation	O
+mechanism	O
+that	O
+controls	O
+expression	O
+of	O
+the	O
+Bacillus	B-GENE
+subtilis	I-GENE
+trpEDCFBA	I-GENE
+operon	I-GENE
+.	O
+
+Single	O
+-	O
+alanine	O
+-	O
+substitution	O
+mutations	O
+had	O
+minimal	O
+,	O
+if	O
+any	O
+,	O
+effects	O
+on	O
+S	O
+-	O
+induced	O
+cell	O
+-	O
+to	O
+-	O
+cell	O
+fusion	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+demonstrate	O
+that	O
+transcription	O
+from	O
+the	O
+MMTV	B-GENE
+5	I-GENE
+'	I-GENE
+LTR	I-GENE
+is	O
+highly	O
+active	O
+in	O
+the	O
+absence	O
+of	O
+Stat5a	B-GENE
+,	O
+a	O
+transcription	O
+factor	O
+that	O
+had	O
+been	O
+shown	O
+previously	O
+to	O
+be	O
+required	O
+for	O
+transcription	O
+from	O
+the	O
+MMTV	B-GENE
+LTR	I-GENE
+.	O
+
+Regional	O
+insertional	O
+mutagenesis	O
+of	O
+specific	O
+genes	O
+on	O
+the	O
+CIC5F11	B-GENE
+/	O
+CIC2B9	B-GENE
+locus	O
+of	O
+Arabidopsis	O
+thaliana	O
+chromosome	O
+5	O
+using	O
+the	O
+Ac	B-GENE
+/	O
+Ds	B-GENE
+transposon	O
+in	O
+combination	O
+with	O
+the	O
+cDNA	O
+scanning	O
+method	O
+.	O
+
+RESULTS	O
+:	O
+CK	B-GENE
+-	O
+MB	B-GENE
+elevation	O
+was	O
+detected	O
+in	O
+313	O
+patients	O
+(	O
+18	O
+.	O
+7	O
+%	O
+)	O
+,	O
+with	O
+1	O
+-	O
+3x	O
+in	O
+12	O
+.	O
+8	O
+%	O
+,	O
+3	O
+-	O
+5x	O
+in	O
+3	O
+.	O
+5	O
+%	O
+and	O
+>	O
+5x	O
+normal	O
+in	O
+2	O
+.	O
+4	O
+%	O
+of	O
+patients	O
+.	O
+
+Thus	O
+,	O
+NART	O
+-	O
+R	O
+performance	O
+may	O
+not	O
+be	O
+a	O
+valid	O
+estimate	O
+of	O
+baseline	O
+IQ	O
+for	O
+patients	O
+with	O
+neurologic	O
+disorders	O
+with	O
+suspected	O
+language	O
+impairment	O
+.	O
+
+Activated	O
+areas	O
+have	O
+been	O
+identified	O
+by	O
+means	O
+of	O
+cross	O
+-	O
+correlation	O
+analysis	O
+.	O
+
+Natural	O
+Haemophilus	O
+influenzae	O
+type	O
+b	O
+capsular	O
+polysaccharide	O
+antibodies	O
+in	O
+412	O
+infants	O
+and	O
+children	O
+from	O
+West	O
+Africa	O
+(	O
+Burkina	O
+-	O
+Faso	O
+)	O
+and	O
+France	O
+:	O
+a	O
+cross	O
+-	O
+sectional	O
+serosurvey	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+identified	O
+Sp1	B-GENE
+and	O
+Sp3	B-GENE
+as	O
+major	O
+factors	O
+binding	O
+to	O
+the	O
+Sp1	B-GENE
+sites	I-GENE
+of	O
+the	O
+p21	B-GENE
+/	O
+WAF1	B-GENE
+/	O
+Cip1	B-GENE
+promoter	O
+in	O
+MG63	O
+cells	O
+through	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+and	O
+showed	O
+that	O
+TSA	O
+treatment	O
+did	O
+not	O
+change	O
+their	O
+binding	O
+activities	O
+.	O
+
+Galoyan	O
+has	O
+summarized	O
+the	O
+results	O
+of	O
+his	O
+discovery	O
+of	O
+cardioactive	O
+neurohormones	O
+.	O
+
+To	O
+study	O
+the	O
+regulation	O
+of	O
+its	O
+expression	O
+,	O
+the	O
+human	B-GENE
+aldehyde	I-GENE
+reductase	I-GENE
+gene	I-GENE
+and	O
+promoter	O
+were	O
+cloned	O
+and	O
+characterized	O
+.	O
+
+The	O
+C2C	B-GENE
+-	O
+Prx	B-GENE
+is	O
+encoded	O
+as	O
+a	O
+preprotein	O
+of	O
+273	O
+amino	O
+acids	O
+containing	O
+a	O
+putative	O
+chloroplast	O
+-	O
+targeting	O
+signal	O
+of	O
+65	O
+amino	O
+acids	O
+at	O
+its	O
+N	O
+-	O
+terminus	O
+.	O
+
+Immediately	O
+before	O
+surgery	O
+patients	O
+received	O
+either	O
+intravenous	O
+hydrocortisone	O
+100	O
+mg	O
+or	O
+placebo	O
+in	O
+random	O
+,	O
+double	O
+-	O
+blind	O
+order	O
+.	O
+
+A	O
+tyrosine	O
+-	O
+based	O
+sorting	O
+signal	O
+in	O
+the	O
+beta2	B-GENE
+integrin	I-GENE
+cytoplasmic	I-GENE
+domain	I-GENE
+mediates	O
+its	O
+recycling	O
+to	O
+the	O
+plasma	O
+membrane	O
+and	O
+is	O
+required	O
+for	O
+ligand	O
+-	O
+supported	O
+migration	O
+.	O
+
+The	O
+injection	O
+of	O
+XDRP1	B-GENE
+protein	I-GENE
+into	O
+fertilized	O
+Xenopus	O
+eggs	O
+blocked	O
+embryonic	O
+cell	O
+division	O
+.	O
+
+Using	O
+transgenic	O
+Xenopus	O
+embryos	O
+,	O
+we	O
+demonstrate	O
+that	O
+the	O
+integrity	O
+of	O
+these	O
+two	O
+sequences	O
+is	O
+necessary	O
+for	O
+correct	O
+spatial	O
+expression	O
+of	O
+a	O
+Xbra2	B-GENE
+promoter	I-GENE
+-	I-GENE
+driven	I-GENE
+reporter	I-GENE
+gene	I-GENE
+.	O
+
+In	O
+order	O
+to	O
+screen	O
+for	O
+such	O
+cofactors	O
+,	O
+we	O
+have	O
+used	O
+a	O
+transcriptionally	O
+inactive	O
+mutant	O
+of	O
+Xenopus	B-GENE
+MEF2D	I-GENE
+in	O
+a	O
+yeast	O
+two	O
+-	O
+hybrid	O
+screen	O
+.	O
+
+NuA4	B-GENE
+has	O
+an	O
+apparent	O
+molecular	O
+mass	O
+of	O
+1	O
+.	O
+3	O
+MDa	O
+.	O
+
+ATF1	B-GENE
+transcription	O
+is	O
+negatively	O
+regulated	O
+by	O
+unsaturated	O
+fatty	O
+acids	O
+and	O
+oxygen	O
+.	O
+
+Mutation	O
+of	O
+TTF	B-GENE
+-	I-GENE
+1	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+(	I-GENE
+TBE	I-GENE
+)	I-GENE
+1	I-GENE
+,	I-GENE
+3	I-GENE
+,	I-GENE
+and	I-GENE
+4	I-GENE
+in	O
+combination	O
+markedly	O
+decreased	O
+transcriptional	O
+activity	O
+of	O
+SP	B-GENE
+-	I-GENE
+A	I-GENE
+promoter	O
+-	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+constructs	O
+containing	O
+SP	B-GENE
+-	I-GENE
+A	I-GENE
+gene	I-GENE
+sequences	O
+from	O
+-	O
+256	O
+to	O
++	O
+45	O
+.	O
+
+Insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+I	I-GENE
+induces	O
+bcl	B-GENE
+-	I-GENE
+2	I-GENE
+promoter	I-GENE
+through	O
+the	O
+transcription	O
+factor	O
+cAMP	B-GENE
+-	I-GENE
+response	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+.	O
+
+Synthesis	O
+of	O
+antisense	O
+RNA	O
+and	O
+S	O
+phase	O
+-	O
+dependent	O
+binding	O
+of	O
+E2F	B-GENE
+complexes	I-GENE
+in	O
+intron	O
+1	O
+.	O
+
+Identification	O
+of	O
+eotaxin	B-GENE
+-	I-GENE
+3	I-GENE
+will	O
+further	O
+promote	O
+our	O
+understanding	O
+of	O
+the	O
+control	O
+of	O
+eosinophil	O
+trafficking	O
+and	O
+other	O
+CCR3	B-GENE
+-	O
+mediated	O
+biological	O
+phenomena	O
+.	O
+
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+plays	O
+a	O
+critical	O
+role	O
+in	O
+activation	O
+of	O
+HIV	O
+-	O
+1	O
+gene	O
+expression	O
+by	O
+cytokines	O
+and	O
+other	O
+stimuli	O
+,	O
+but	O
+the	O
+signal	O
+transduction	O
+pathways	O
+that	O
+regulate	O
+the	O
+switch	O
+from	O
+latent	O
+to	O
+productive	O
+infection	O
+have	O
+not	O
+been	O
+defined	O
+.	O
+
+These	O
+studies	O
+suggest	O
+that	O
+MAPK	B-GENE
+acts	O
+by	O
+stimulating	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+a	O
+subsequent	O
+physical	O
+and	O
+functional	O
+interaction	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+with	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+,	O
+resulting	O
+in	O
+a	O
+complex	O
+that	O
+synergistically	O
+transactivates	O
+the	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+LTR	I-GENE
+.	O
+
+ERK	B-GENE
+MAP	B-GENE
+kinase	I-GENE
+links	O
+cytokine	O
+signals	O
+to	O
+activation	O
+of	O
+latent	O
+HIV	O
+-	O
+1	O
+infection	O
+by	O
+stimulating	O
+a	O
+cooperative	O
+interaction	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+.	O
+
+A	O
+human	O
+nuclear	O
+-	O
+localized	O
+chaperone	O
+that	O
+regulates	O
+dimerization	O
+,	O
+DNA	O
+binding	O
+,	O
+and	O
+transcriptional	O
+activity	O
+of	O
+bZIP	B-GENE
+proteins	I-GENE
+.	O
+
+Clinical	O
+differentiation	O
+of	O
+patients	O
+with	O
+mild	O
+diplegic	O
+cerebral	O
+palsy	O
+(	O
+CP	O
+)	O
+and	O
+idiopathic	O
+toe	O
+walking	O
+(	O
+ITW	O
+)	O
+can	O
+be	O
+difficult	O
+.	O
+
+Sputum	B-GENE
+IL	I-GENE
+-	I-GENE
+8	I-GENE
+and	O
+MPO	B-GENE
+were	O
+significantly	O
+increased	O
+after	O
+BPT	O
+in	O
+both	O
+TDI	O
+-	O
+and	O
+grain	O
+dust	O
+-	O
+asthma	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Montelukast	O
+reduces	O
+airway	O
+eosinophilic	O
+inflammation	O
+in	O
+asthma	O
+:	O
+a	O
+randomized	O
+,	O
+controlled	O
+trial	O
+.	O
+
+Here	O
+,	O
+we	O
+demonstrate	O
+that	O
+kinase	O
+-	O
+dead	O
+but	O
+not	O
+wild	O
+-	O
+type	O
+forms	O
+of	O
+Fyn	B-GENE
+,	O
+Lck	B-GENE
+,	O
+and	O
+ZAP	B-GENE
+-	I-GENE
+70	I-GENE
+block	O
+70Z	O
+Cbl	B-GENE
+-	O
+mediated	O
+NFAT	B-GENE
+activation	O
+.	O
+
+Substitutions	O
+of	O
+region	O
+I	O
+with	O
+synthetic	O
+sequences	O
+showed	O
+that	O
+no	O
+specific	O
+sequence	O
+but	O
+rather	O
+repeats	O
+of	O
+three	O
+or	O
+more	O
+consecutive	O
+adenines	O
+or	O
+thymines	O
+,	O
+without	O
+interruption	O
+by	O
+guanine	O
+or	O
+cytosine	O
+,	O
+are	O
+required	O
+for	O
+the	O
+ARS	O
+activity	O
+.	O
+
+In	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+PHO85	B-GENE
+encodes	O
+a	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+Cdk	B-GENE
+)	O
+catalytic	O
+subunit	O
+with	O
+multiple	O
+regulatory	O
+roles	O
+thought	O
+to	O
+be	O
+specified	O
+by	O
+association	O
+with	O
+different	O
+cyclin	B-GENE
+partners	O
+(	O
+Pcls	B-GENE
+)	O
+.	O
+
+Mutants	O
+with	O
+mild	O
+lace	B-GENE
+alleles	I-GENE
+grow	O
+to	O
+become	O
+adults	O
+with	O
+multiple	O
+aberrant	O
+morphologies	O
+in	O
+the	O
+appendages	O
+,	O
+compound	O
+eye	O
+,	O
+and	O
+bristles	O
+.	O
+
+In	O
+fact	O
+,	O
+SPT	B-GENE
+activity	O
+in	O
+the	O
+fly	O
+expressing	O
+epitope	O
+-	O
+tagged	O
+Lace	B-GENE
+was	O
+absorbed	O
+by	O
+epitope	O
+-	O
+specific	O
+antibody	O
+.	O
+
+These	O
+results	O
+show	O
+that	O
+targeting	O
+of	O
+Ras	B-GENE
+-	O
+GAP	B-GENE
+could	O
+represent	O
+a	O
+novel	O
+anticancer	O
+approach	O
+.	O
+
+EB	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+a	O
+tyrosine	B-GENE
+kinase	I-GENE
+signal	I-GENE
+transduction	I-GENE
+gene	I-GENE
+,	O
+is	O
+transcriptionally	O
+activated	O
+in	O
+the	O
+t	O
+(	O
+1	O
+;	O
+19	O
+)	O
+subset	O
+of	O
+pre	O
+-	O
+B	O
+ALL	O
+,	O
+which	O
+express	O
+oncoprotein	O
+E2a	B-GENE
+-	O
+Pbx1	B-GENE
+.	O
+
+BCL6	B-GENE
+encodes	O
+a	O
+POZ	B-GENE
+/	I-GENE
+Zn	I-GENE
+finger	I-GENE
+protein	I-GENE
+,	O
+a	O
+structure	O
+similar	O
+to	O
+that	O
+of	O
+many	O
+Drosophila	O
+developmental	O
+regulators	O
+and	O
+to	O
+another	O
+protein	O
+involved	O
+in	O
+a	O
+human	O
+hematopoietic	O
+malignancy	O
+,	O
+PLZF	B-GENE
+.	O
+
+Beta	B-GENE
+1	I-GENE
+integrin	I-GENE
+-	O
+and	O
+proteoglycan	O
+-	O
+mediated	O
+stimulation	O
+of	O
+T	O
+lymphoma	O
+cell	O
+adhesion	O
+and	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+signaling	O
+by	O
+thrombospondin	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+thrombospondin	B-GENE
+-	I-GENE
+1	I-GENE
+peptides	I-GENE
+.	O
+
+Optical	O
+CD	O
+,	O
+and	O
+spectral	O
+and	O
+activity	O
+analyses	O
+were	O
+used	O
+to	O
+examine	O
+reactivity	O
+of	O
+HO	B-GENE
+isozymes	I-GENE
+with	O
+NO	O
+species	O
+produced	O
+by	O
+NO	O
+donors	O
+.	O
+
+The	O
+phosphotransferase	O
+system	O
+(	O
+PTS	O
+)	O
+of	O
+Streptomyces	O
+coelicolor	O
+identification	O
+and	O
+biochemical	O
+analysis	O
+of	O
+a	O
+histidine	B-GENE
+phosphocarrier	I-GENE
+protein	I-GENE
+HPr	B-GENE
+encoded	O
+by	O
+the	O
+gene	O
+ptsH	B-GENE
+.	O
+
+Serum	O
+concentrations	O
+of	O
+bone	B-GENE
+specific	I-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+(	O
+BALP	B-GENE
+)	O
+and	O
+osteocalcin	B-GENE
+(	O
+bone	B-GENE
+Gla	I-GENE
+protein	I-GENE
+,	O
+BGP	B-GENE
+)	O
+,	O
+urinary	O
+levels	O
+of	O
+pyridinoline	O
+(	O
+Pyr	O
+)	O
+and	O
+deoxypyridinoline	O
+(	O
+Dpyr	O
+)	O
+and	O
+computed	O
+tomography	O
+(	O
+CT	O
+)	O
+measurements	O
+of	O
+the	O
+cross	O
+-	O
+sectional	O
+areas	O
+of	O
+the	O
+vertebrae	O
+and	O
+the	O
+femurs	O
+,	O
+the	O
+apparent	O
+density	O
+of	O
+cancellous	O
+bone	O
+in	O
+the	O
+vertebrae	O
+,	O
+and	O
+the	O
+volume	O
+and	O
+the	O
+material	O
+density	O
+of	O
+cortical	O
+bone	O
+in	O
+the	O
+femurs	O
+were	O
+determined	O
+in	O
+126	O
+boys	O
+and	O
+143	O
+girls	O
+,	O
+ages	O
+7	O
+-	O
+18	O
+years	O
+.	O
+
+In	O
+another	O
+study	O
+,	O
+intravenous	O
+administration	O
+of	O
+devazepide	O
+,	O
+a	O
+specific	O
+cholecystokinin	B-GENE
+-	I-GENE
+A	I-GENE
+receptor	I-GENE
+antagonist	O
+,	O
+at	O
+a	O
+dose	O
+of	O
+0	O
+.	O
+1	O
+mg	O
+/	O
+kg	O
+/	O
+hr	O
+was	O
+begun	O
+15	O
+min	O
+before	O
+postprandial	O
+saline	O
+intake	O
+and	O
+continued	O
+for	O
+1	O
+hr	O
+.	O
+
+This	O
+cluster	O
+consisted	O
+of	O
+four	O
+apparently	O
+unrelated	O
+ESTs	O
+and	O
+two	O
+genes	O
+,	O
+pregnancy	B-GENE
+-	I-GENE
+associated	I-GENE
+plasma	I-GENE
+protein	I-GENE
+-	I-GENE
+A	I-GENE
+(	O
+PAPP	B-GENE
+-	I-GENE
+A	I-GENE
+)	O
+and	O
+a	O
+novel	O
+gene	O
+(	O
+tentatively	O
+named	O
+EST	B-GENE
+-	I-GENE
+YD1	I-GENE
+)	O
+.	O
+
+Prognostic	O
+value	O
+of	O
+a	O
+treadmill	O
+exercise	O
+score	O
+in	O
+symptomatic	O
+patients	O
+with	O
+nonspecific	O
+ST	O
+-	O
+T	O
+abnormalities	O
+on	O
+resting	O
+ECG	O
+.	O
+
+Structural	O
+changes	O
+in	O
+the	O
+C	O
+-	O
+terminus	O
+of	O
+Ca2	O
++	O
+-	O
+bound	O
+rat	B-GENE
+S100B	I-GENE
+(	O
+beta	B-GENE
+beta	I-GENE
+)	O
+upon	O
+binding	O
+to	O
+a	O
+peptide	O
+derived	O
+from	O
+the	O
+C	O
+-	O
+terminal	O
+regulatory	O
+domain	O
+of	O
+p53	B-GENE
+.	O
+
+We	O
+propose	O
+that	O
+Gly84	O
+is	O
+part	O
+of	O
+a	O
+putative	O
+"	O
+oxyanion	O
+hole	O
+"	O
+involved	O
+in	O
+the	O
+stabilization	O
+of	O
+the	O
+transition	O
+state	O
+similar	O
+to	O
+the	O
+C	B-GENE
+group	I-GENE
+of	O
+the	O
+esterase	B-GENE
+/	O
+lipase	B-GENE
+family	O
+.	O
+
+The	O
+solution	O
+structure	O
+of	O
+the	O
+adduct	O
+derived	O
+from	O
+the	O
+covalent	O
+bonding	O
+of	O
+the	O
+fjord	O
+region	O
+(	O
++	O
+)	O
+-	O
+(	O
+11S	O
+,	O
+12R	O
+,	O
+13R	O
+,	O
+14S	O
+)	O
+stereoisomer	O
+of	O
+anti	O
+-	O
+11	O
+,	O
+12	O
+-	O
+dihydroxy	O
+-	O
+13	O
+,	O
+14	O
+-	O
+epoxy	O
+-	O
+11	O
+,	O
+12	O
+,	O
+13	O
+,	O
+14	O
+-	O
+tetrahydrobenzo	O
+[	O
+g	O
+]	O
+chrysene	O
+,	O
+(	O
++	O
+)	O
+-	O
+anti	O
+-	O
+B	O
+[	O
+g	O
+]	O
+CDE	O
+,	O
+to	O
+the	O
+exocyclic	O
+N	O
+(	O
+6	O
+)	O
+amino	O
+group	O
+of	O
+the	O
+adenine	O
+residue	O
+dA6	O
+,	O
+(	O
+designated	O
+(	O
++	O
+)	O
+-	O
+trans	O
+-	O
+anti	O
+-	O
+(	O
+B	O
+[	O
+g	O
+]	O
+C	O
+)	O
+dA6	O
+)	O
+,	O
+positioned	O
+opposite	O
+a	O
+thymine	O
+residue	O
+dT17	O
+in	O
+the	O
+DNA	O
+sequence	O
+context	O
+d	O
+(	O
+C1	O
+-	O
+T2	O
+-	O
+C3	O
+-	O
+T4	O
+-	O
+C5	O
+-	O
+(	O
+B	O
+[	O
+g	O
+]	O
+C	O
+)	O
+A6	O
+-	O
+C7	O
+-	O
+T8	O
+-	O
+T9	O
+-	O
+C10	O
+-	O
+C11	O
+)	O
+.	O
+d	O
+(	O
+G12	O
+-	O
+G13	O
+-	O
+A14	O
+-	O
+A15	O
+-	O
+G16	O
+-	O
+T17	O
+-	O
+G18	O
+-	O
+A19	O
+-	O
+G20	O
++	O
++	O
++	O
+-	O
+A21	O
+-	O
+G22	O
+)	O
+(	O
+designated	O
+(	O
+B	O
+[	O
+g	O
+]	O
+C	O
+)	O
+dA	O
+.	O
+dT	O
+11	O
+-	O
+mer	O
+duplex	O
+)	O
+,	O
+has	O
+been	O
+studied	O
+using	O
+structural	O
+information	O
+derived	O
+from	O
+NMR	O
+data	O
+in	O
+combination	O
+with	O
+molecular	O
+dynamics	O
+(	O
+MD	O
+)	O
+calculations	O
+.	O
+
+Since	O
+sildenafil	O
+came	O
+on	O
+the	O
+market	O
+,	O
+it	O
+seems	O
+that	O
+the	O
+place	O
+of	O
+MUSE	O
+is	O
+reduced	O
+because	O
+comparative	O
+studies	O
+give	O
+better	O
+results	O
+for	O
+sildenafil	O
+than	O
+MUSE	O
+(	O
+70	O
+%	O
+vs	O
+40	O
+%	O
+)	O
+and	O
+of	O
+course	O
+with	O
+a	O
+better	O
+acceptance	O
+.	O
+
+Serum	O
+antibodies	O
+were	O
+detected	O
+in	O
+at	O
+least	O
+95	O
+%	O
+of	O
+the	O
+infected	O
+guinea	O
+pigs	O
+between	O
+4	O
+-	O
+30	O
+WPI	O
+and	O
+rats	O
+between	O
+3	O
+-	O
+16	O
+WPI	O
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+results	O
+show	O
+that	O
+once	O
+daily	O
+oral	O
+valganciclovir	O
+can	O
+produce	O
+exposures	O
+of	O
+ganciclovir	O
+(	O
+AUC24	O
+)	O
+exceeding	O
+those	O
+attained	O
+using	O
+intravenous	O
+ganciclovir	O
+10	O
+mg	O
+/	O
+kg	O
+.	O
+
+Except	O
+for	O
+nonperfusion	O
+of	O
+neurosensory	O
+retinal	O
+vessels	O
+at	O
+a	O
+light	O
+dose	O
+of	O
+150	O
+J	O
+/	O
+cm2	O
+,	O
+no	O
+other	O
+adverse	O
+events	O
+were	O
+of	O
+concern	O
+.	O
+
+Except	O
+for	O
+nonperfusion	O
+of	O
+neurosensory	O
+retinal	O
+vessels	O
+at	O
+a	O
+light	O
+dose	O
+of	O
+150	O
+J	O
+/	O
+cm2	O
+,	O
+no	O
+other	O
+adverse	O
+events	O
+were	O
+of	O
+concern	O
+.	O
+
+The	O
+healing	O
+rate	O
+in	O
+HIV	O
+-	O
+positive	O
+patients	O
+was	O
+66	O
+percent	O
+after	O
+14	O
+weeks	O
+and	O
+100	O
+percent	O
+after	O
+32	O
+weeks	O
+;	O
+the	O
+corresponding	O
+figures	O
+for	O
+patients	O
+with	O
+acquired	O
+immunodeficiency	O
+syndrome	O
+were	O
+0	O
+and	O
+50	O
+percent	O
+.	O
+
+The	O
+P	B-GENE
+mRNA	I-GENE
+also	O
+contains	O
+a	O
+third	O
+ORF	O
+for	O
+the	O
+V	B-GENE
+protein	I-GENE
+,	O
+although	O
+it	O
+is	O
+unclear	O
+how	O
+or	O
+whether	O
+this	O
+ORF	O
+is	O
+accessed	O
+.	O
+
+A	O
+genetic	O
+screen	O
+in	O
+yeast	O
+has	O
+allowed	O
+us	O
+to	O
+identify	O
+a	O
+novel	O
+transcriptional	O
+factor	O
+binding	O
+to	O
+the	O
+GlRE	O
+,	O
+i	O
+.	O
+e	O
+.	O
+the	O
+chicken	B-GENE
+ovalbumin	I-GENE
+upstream	I-GENE
+promoter	I-GENE
+-	I-GENE
+transcription	I-GENE
+factor	I-GENE
+II	I-GENE
+(	O
+COUP	B-GENE
+-	I-GENE
+TFII	I-GENE
+)	O
+.	O
+
+We	O
+have	O
+cloned	O
+the	O
+single	O
+-	O
+copy	O
+gene	O
+for	O
+the	O
+trans	B-GENE
+-	I-GENE
+spliceosomal	I-GENE
+U5	I-GENE
+snRNA	I-GENE
+from	O
+the	O
+trypanosomatid	O
+species	O
+Leptomonas	O
+seymouri	O
+,	O
+using	O
+U5	B-GENE
+RNA	I-GENE
+affinity	O
+selection	O
+and	O
+cDNA	O
+cloning	O
+.	O
+
+The	O
+MMPI	O
+-	O
+A	O
+(	O
+Butcher	O
+et	O
+al	O
+.	O
+,	O
+1992	O
+)	O
+,	O
+like	O
+the	O
+older	O
+MMPI	O
+(	O
+Hathaway	O
+&	O
+McKinley	O
+,	O
+1983	O
+)	O
+,	O
+distinguishes	O
+between	O
+anorexia	O
+and	O
+bulimia	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+phosphatidyl	O
+inositol	O
+4	O
+,	O
+5	O
+bisphosphate	O
+(	O
+PIP2	O
+)	O
+hydrolysis	O
+requires	O
+direct	O
+phosphorylation	O
+at	O
+tyrosine	O
+residue	O
+of	O
+the	O
+PLC	B-GENE
+-	I-GENE
+gamma1	I-GENE
+isozyme	I-GENE
+.	O
+
+A	O
+G22V	B-GENE
+mutant	I-GENE
+of	O
+M	B-GENE
+-	I-GENE
+Ras	I-GENE
+was	O
+constitutively	O
+active	O
+and	O
+its	O
+expression	O
+in	O
+an	O
+interleukin	B-GENE
+-	I-GENE
+3	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+-	O
+dependent	O
+mast	O
+cell	O
+/	O
+megakaryocyte	O
+cell	O
+line	O
+resulted	O
+in	O
+increased	O
+survival	O
+in	O
+the	O
+absence	O
+of	O
+IL	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+increased	O
+growth	O
+in	O
+IL	B-GENE
+-	I-GENE
+4	I-GENE
+,	O
+and	O
+,	O
+at	O
+high	O
+expression	O
+levels	O
+,	O
+in	O
+factor	O
+-	O
+independent	O
+growth	O
+.	O
+
+Mammalian	B-GENE
+M	I-GENE
+-	I-GENE
+Ras	I-GENE
+and	O
+a	O
+Caenorhabditis	O
+elegans	O
+orthologue	O
+exhibit	O
+conserved	O
+structural	O
+features	O
+,	O
+and	O
+these	O
+are	O
+likely	O
+to	O
+mediate	O
+activation	O
+of	O
+distinctive	O
+signaling	O
+paths	O
+that	O
+function	O
+in	O
+parallel	O
+to	O
+those	O
+downstream	O
+of	O
+p21	B-GENE
+Ras	I-GENE
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+PecS	B-GENE
+attenuates	O
+pelD	B-GENE
+and	O
+pelE	B-GENE
+expression	O
+rather	O
+than	O
+acting	O
+as	O
+a	O
+true	O
+repressor	O
+like	O
+KdgR	B-GENE
+.	O
+
+These	O
+observations	O
+establish	O
+that	O
+RsmC	B-GENE
+negatively	O
+regulates	O
+rsmB	B-GENE
+transcription	O
+but	O
+positively	O
+affects	O
+RsmA	B-GENE
+production	O
+.	O
+
+All	O
+were	O
+experienced	O
+hearing	O
+aid	O
+users	O
+who	O
+wore	O
+linear	O
+Class	O
+D	O
+instruments	O
+with	O
+input	O
+compression	O
+limiting	O
+at	O
+the	O
+time	O
+of	O
+their	O
+enrollment	O
+in	O
+this	O
+study	O
+.	O
+
+Ribonuclease	O
+protection	O
+assays	O
+revealed	O
+that	O
+hmg1	B-GENE
+and	O
+hmg2	B-GENE
+are	O
+differentially	O
+expressed	O
+in	O
+a	O
+developmentally	O
+-	O
+and	O
+spatially	O
+-	O
+modulated	O
+manner	O
+during	O
+morphogenesis	O
+of	O
+specialized	O
+terpenoid	O
+-	O
+containing	O
+pigment	O
+glands	O
+in	O
+embryos	O
+.	O
+
+Inactivation	O
+of	O
+the	O
+Neurospora	B-GENE
+crassa	I-GENE
+mitochondrial	I-GENE
+outer	I-GENE
+membrane	I-GENE
+protein	I-GENE
+TOM70	I-GENE
+by	O
+repeat	O
+-	O
+induced	O
+point	O
+mutation	O
+(	O
+RIP	O
+)	O
+causes	O
+defects	O
+in	O
+mitochondrial	O
+protein	O
+import	O
+and	O
+morphology	O
+.	O
+
+Recently	O
+,	O
+cell	O
+-	O
+surface	O
+TRAIL	B-GENE
+has	O
+been	O
+shown	O
+to	O
+be	O
+expressed	O
+by	O
+activated	O
+human	O
+and	O
+mouse	O
+T	O
+lymphocytes	O
+,	O
+raising	O
+the	O
+possibility	O
+that	O
+TRAIL	B-GENE
+might	O
+be	O
+involved	O
+in	O
+T	O
+cell	O
+-	O
+mediated	O
+cytotoxicity	O
+and	O
+/	O
+or	O
+immune	O
+regulation	O
+.	O
+
+A	O
+panel	O
+of	O
+pharmacologic	O
+inhibitors	O
+was	O
+used	O
+to	O
+investigate	O
+the	O
+signal	O
+transduction	O
+pathways	O
+involved	O
+in	O
+TRAIL	B-GENE
+gene	I-GENE
+induction	O
+following	O
+T	O
+lymphocyte	O
+activation	O
+.	O
+
+Defective	O
+provirus	O
+genomes	O
+of	O
+human	O
+T	O
+-	O
+cell	O
+leukemia	O
+virus	O
+type	O
+I	O
+are	O
+frequently	O
+detected	O
+in	O
+lymphocytes	O
+from	O
+infected	O
+individuals	O
+and	O
+in	O
+infected	O
+cell	O
+lines	O
+.	O
+
+A	O
+total	O
+of	O
+174	O
+primer	O
+pairs	O
+gave	O
+interpretable	O
+banding	O
+patterns	O
+,	O
+137	O
+(	O
+79	O
+%	O
+)	O
+of	O
+which	O
+revealed	O
+at	O
+least	O
+two	O
+alleles	O
+on	O
+native	O
+polyacrylamide	O
+gels	O
+.	O
+
+A	O
+population	O
+pharmacokinetic	O
+study	O
+of	O
+cyclosporin	O
+in	O
+organ	O
+transplant	O
+patients	O
+,	O
+including	O
+elderly	O
+allograft	O
+recipients	O
+up	O
+to	O
+75	O
+years	O
+of	O
+age	O
+,	O
+did	O
+not	O
+identify	O
+age	O
+as	O
+a	O
+covariable	O
+influencing	O
+cyclosporin	O
+pharmacokinetics	O
+.	O
+
+Immunofluoresence	O
+data	O
+indicated	O
+that	O
+once	O
+bound	O
+to	O
+the	O
+mutant	O
+receptor	O
+,	O
+fluorescent	O
+-	O
+labeled	O
+RAP	B-GENE
+co	O
+-	O
+localized	O
+with	O
+markers	O
+of	O
+the	O
+endosomal	O
+pathway	O
+,	O
+whereas	O
+,	O
+in	O
+cells	O
+expressing	O
+the	O
+wild	O
+-	O
+type	O
+receptor	O
+,	O
+RAP	B-GENE
+fluorescence	O
+co	O
+-	O
+localized	O
+with	O
+lysosomal	O
+markers	O
+.	O
+
+Interleukin	B-GENE
+-	I-GENE
+12	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+12	I-GENE
+)	O
+is	O
+a	O
+cytokine	O
+produced	O
+by	O
+peripheral	O
+blood	O
+mononuclear	O
+cells	O
+(	O
+PBMC	O
+)	O
+that	O
+causes	O
+interferon	B-GENE
+-	I-GENE
+gamma	I-GENE
+(	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+)	O
+production	O
+and	O
+enhancement	O
+of	O
+cell	O
+-	O
+mediated	O
+cytotoxicity	O
+.	O
+
+IL	B-GENE
+-	I-GENE
+12	I-GENE
+production	O
+was	O
+correlated	O
+with	O
+C3a	O
+concentration	O
+measured	O
+at	O
+the	O
+outlet	O
+of	O
+hemodialyzer	O
+after	O
+15	O
+min	O
+of	O
+dialysis	O
+(	O
+r	O
+=	O
+0	O
+.	O
+69	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+In	O
+HeLa	O
+cells	O
+,	O
+the	O
+JNKK2	B-GENE
+-	O
+JNK1	B-GENE
+fusion	O
+protein	O
+showed	O
+significant	O
+JNK	B-GENE
+activity	O
+,	O
+which	O
+was	O
+comparable	O
+with	O
+that	O
+of	O
+JNK1	B-GENE
+activated	O
+by	O
+many	O
+stimuli	O
+and	O
+activators	O
+,	O
+including	O
+EGF	B-GENE
+,	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+,	O
+anisomycin	O
+,	O
+UV	O
+irradiation	O
+,	O
+MEKK1	B-GENE
+,	O
+and	O
+small	B-GENE
+GTP	I-GENE
+binding	I-GENE
+proteins	I-GENE
+Rac1	I-GENE
+and	O
+Cdc42Hs	B-GENE
+.	O
+
+J	O
+.	O
+
+Our	O
+results	O
+implicate	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+RII	I-GENE
+as	O
+a	O
+direct	O
+target	O
+of	O
+EWS	B-GENE
+-	O
+FLI1	B-GENE
+.	O
+
+The	O
+reduction	O
+in	O
+saturated	O
+fatty	O
+acids	O
+intake	O
+led	O
+to	O
+modest	O
+(	O
+but	O
+in	O
+group	O
+1	O
+significant	O
+)	O
+0	O
+.	O
+15	O
+mmol	O
+/	O
+l	O
+(	O
+2	O
+.	O
+5	O
+%	O
+)	O
+reduction	O
+in	O
+total	O
+serum	O
+cholesterol	O
+level	O
+.	O
+
+Secondly	O
+,	O
+an	O
+ethanol	O
+repression	O
+autoregulation	O
+(	O
+ERA	O
+)	O
+/	O
+twelve	O
+-	O
+fold	O
+TA	O
+repeat	O
+(	O
+TAB	O
+)	O
+repressor	O
+element	O
+was	O
+identified	O
+within	O
+the	O
+promoter	O
+region	O
+of	O
+the	O
+GLK1	B-GENE
+gene	I-GENE
+.	O
+
+A	O
+crucial	O
+transcription	O
+factor	O
+in	O
+this	O
+process	O
+is	O
+STAT6	B-GENE
+,	O
+which	O
+binds	O
+to	O
+a	O
+specific	O
+DNA	O
+element	O
+upon	O
+cytokine	O
+activation	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Congenital	O
+horizontal	O
+tarsal	O
+kink	O
+is	O
+rare	O
+and	O
+its	O
+cause	O
+is	O
+unknown	O
+.	O
+
+A	O
+local	O
+,	O
+high	O
+-	O
+density	O
+,	O
+single	O
+-	O
+nucleotide	O
+polymorphism	O
+map	O
+used	O
+to	O
+clone	O
+Caenorhabditis	B-GENE
+elegans	I-GENE
+cdf	I-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+This	O
+machinery	O
+involves	O
+a	O
+secondary	O
+structure	O
+,	O
+SECIS	O
+element	O
+,	O
+in	O
+the	O
+selenoprotein	B-GENE
+-	O
+encoding	O
+mRNA	O
+,	O
+directing	O
+selenocysteine	O
+insertion	O
+at	O
+the	O
+position	O
+of	O
+an	O
+opal	O
+(	O
+UGA	O
+)	O
+codon	O
+,	O
+normally	O
+conferring	O
+termination	O
+of	O
+translation	O
+.	O
+
+High	O
+-	O
+level	O
+expression	O
+in	O
+Escherichia	O
+coli	O
+of	O
+selenocysteine	O
+-	O
+containing	O
+rat	B-GENE
+thioredoxin	I-GENE
+reductase	I-GENE
+utilizing	O
+gene	O
+fusions	O
+with	O
+engineered	O
+bacterial	O
+-	O
+type	O
+SECIS	O
+elements	O
+and	O
+co	O
+-	O
+expression	O
+with	O
+the	O
+selA	B-GENE
+,	O
+selB	B-GENE
+and	O
+selC	B-GENE
+genes	I-GENE
+.	O
+
+In	O
+Wnt	B-GENE
+signaling	O
+,	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+and	O
+plakoglobin	B-GENE
+transduce	O
+signals	O
+to	O
+the	O
+nucleus	O
+through	O
+interactions	O
+with	O
+TCF	B-GENE
+-	I-GENE
+type	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+Assembly	O
+of	O
+a	O
+complex	O
+between	O
+FAK	B-GENE
+and	O
+Src	B-GENE
+kinases	I-GENE
+may	O
+serve	O
+to	O
+regulate	O
+the	O
+subcellular	O
+localization	O
+and	O
+the	O
+enzymatic	O
+activity	O
+of	O
+members	O
+of	O
+the	O
+Src	B-GENE
+family	I-GENE
+of	O
+kinases	O
+.	O
+
+Our	O
+study	O
+also	O
+demonstrated	O
+significant	O
+increases	O
+in	O
+the	O
+number	O
+of	O
+larger	O
+myelinated	O
+fibers	O
+crossing	O
+the	O
+repair	O
+site	O
+in	O
+comparison	O
+with	O
+the	O
+neonatal	O
+and	O
+adult	O
+groups	O
+(	O
+p	O
+<	O
+0	O
+.	O
+04	O
+)	O
+.	O
+
+Cortical	O
+dysplasias	O
+,	O
+genetics	O
+,	O
+and	O
+epileptogenesis	O
+.	O
+
+In	O
+the	O
+work	O
+reported	O
+here	O
+,	O
+we	O
+used	O
+peptide	O
+mapping	O
+,	O
+mass	O
+spectrometry	O
+,	O
+and	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+to	O
+identify	O
+two	O
+sets	O
+of	O
+pAP	B-GENE
+phosphorylation	O
+sites	O
+.	O
+
+Both	O
+HERV	O
+-	O
+K	O
+type	O
+1	O
+and	O
+2	O
+clones	O
+were	O
+isolated	O
+.	O
+
+Duch	O
+,	O
+and	O
+F	O
+.	O
+
+At	O
+all	O
+time	O
+-	O
+points	O
+,	O
+most	O
+patients	O
+(	O
+>	O
+/	O
+=	O
+87	O
+%	O
+)	O
+were	O
+receiving	O
+irbesartan	O
+/	O
+HCTZ	O
+alone	O
+.	O
+
+Modification	O
+of	O
+dopamine	B-GENE
+D2	I-GENE
+receptor	I-GENE
+activity	O
+by	O
+pergolide	O
+in	O
+Parkinson	O
+'	O
+s	O
+disease	O
+:	O
+an	O
+in	O
+vivo	O
+study	O
+by	O
+PET	O
+.	O
+
+High	O
+-	O
+affinity	O
+binding	O
+sites	O
+for	O
+both	O
+GR	B-GENE
+and	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+nucleoproteins	I-GENE
+were	O
+identified	O
+at	O
+adjacent	O
+elements	O
+within	O
+the	O
+nGRE	O
+.	O
+
+When	O
+the	O
+73	O
+-	O
+bp	O
+fragment	O
+was	O
+fused	O
+to	O
+an	O
+alpha1	B-GENE
+-	I-GENE
+globin	I-GENE
+promoter	O
+-	O
+CAT	B-GENE
+construct	O
+and	O
+cotransfected	O
+with	O
+CCAAT	B-GENE
+transcription	I-GENE
+factor	I-GENE
+1	I-GENE
+(	O
+CTF1	B-GENE
+)	O
+/	O
+NF1	B-GENE
+into	O
+Drosophila	O
+Schneider	O
+SL2	O
+insect	O
+cells	O
+(	O
+which	O
+lack	O
+NF1	B-GENE
+-	I-GENE
+like	I-GENE
+proteins	I-GENE
+)	O
+trans	O
+-	O
+activation	O
+of	O
+CAT	B-GENE
+activity	O
+was	O
+observed	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+showed	O
+a	O
+rapid	O
+corresponding	O
+increase	O
+in	O
+p21WAF1	B-GENE
+/	O
+CIP1	B-GENE
+protein	O
+,	O
+whereas	O
+protein	O
+levels	O
+of	O
+another	O
+member	O
+of	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+inhibitor	I-GENE
+family	I-GENE
+,	O
+p27kip1	B-GENE
+,	O
+were	O
+unchanged	O
+.	O
+
+Aggregation	O
+of	O
+vHnf1	B-GENE
+-	O
+deficient	O
+embryonic	O
+stem	O
+cells	O
+with	O
+wild	O
+-	O
+type	O
+tetraploid	O
+embryos	O
+,	O
+which	O
+contribute	O
+exclusively	O
+to	O
+extraembryonic	O
+tissues	O
+,	O
+rescues	O
+periimplantation	O
+lethality	O
+and	O
+allows	O
+development	O
+to	O
+progress	O
+to	O
+early	O
+organogenesis	O
+.	O
+
+nos	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+nos	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+two	O
+genes	O
+related	O
+to	O
+Drosophila	B-GENE
+nanos	I-GENE
+,	O
+regulate	O
+primordial	O
+germ	O
+cell	O
+development	O
+and	O
+survival	O
+in	O
+Caenorhabditis	O
+elegans	O
+.	O
+
+Although	O
+upstream	O
+regulators	O
+of	O
+Tec	B-GENE
+family	I-GENE
+kinases	I-GENE
+are	O
+relatively	O
+well	O
+characterized	O
+,	O
+little	O
+is	O
+known	O
+of	O
+the	O
+downstream	O
+effectors	O
+of	O
+these	O
+enzymes	O
+.	O
+
+Efficient	O
+phosphorylation	O
+of	O
+BRDG1	B-GENE
+by	O
+Tec	B-GENE
+required	O
+the	O
+PH	B-GENE
+and	O
+SH2	B-GENE
+domains	I-GENE
+as	O
+well	O
+as	O
+the	O
+kinase	O
+domain	O
+of	O
+the	O
+latter	O
+.	O
+
+CONCLUSION	O
+:	O
+These	O
+findings	O
+imply	O
+that	O
+eotaxin	O
+either	O
+is	O
+mechanistically	O
+involved	O
+in	O
+acute	O
+asthma	O
+or	O
+serves	O
+as	O
+a	O
+biomarker	O
+for	O
+activity	O
+of	O
+the	O
+CCR3	B-GENE
+receptor	I-GENE
+ligand	I-GENE
+system	O
+,	O
+which	O
+is	O
+functionally	O
+linked	O
+to	O
+asthma	O
+.	O
+
+The	O
+expression	O
+analysis	O
+of	O
+the	O
+KlHIS4	B-GENE
+gene	I-GENE
+under	O
+phosphate	O
+starvation	O
+or	O
+high	O
+adenine	O
+supply	O
+shows	O
+that	O
+factors	O
+,	O
+such	O
+as	O
+Bas1	B-GENE
+or	O
+Bas2	B-GENE
+,	O
+involved	O
+in	O
+the	O
+basal	O
+control	O
+may	O
+also	O
+operate	O
+in	O
+a	O
+different	O
+way	O
+in	O
+K	O
+.	O
+lactis	O
+.	O
+
+These	O
+thyroid	O
+hormone	O
+changes	O
+may	O
+be	O
+mediated	O
+in	O
+part	O
+by	O
+cytokines	O
+or	O
+other	O
+inflammatory	O
+mediators	O
+,	O
+acting	O
+at	O
+the	O
+level	O
+of	O
+the	O
+hypothalamus	O
+and	O
+pituitary	O
+gland	O
+,	O
+the	O
+thyroid	O
+gland	O
+,	O
+and	O
+the	O
+hepatic	B-GENE
+deiodinase	I-GENE
+system	O
+.	O
+
+ESS	O
+type	O
+1	O
+,	O
+with	O
+FT3	O
+low	O
+and	O
+FT4	O
+and	O
+TSH	B-GENE
+normal	O
+,	O
+is	O
+the	O
+most	O
+frequent	O
+form	O
+.	O
+
+METHODS	O
+:	O
+We	O
+studied	O
+20	O
+symptomatic	O
+patients	O
+with	O
+HOCM	O
+(	O
+12	O
+men	O
+)	O
+,	O
+mean	O
+age	O
+52	O
++	O
+/	O
+-	O
+17	O
+years	O
+,	O
+before	O
+and	O
+after	O
+septal	O
+reduction	O
+using	O
+echocardiography	O
+and	O
+electrocardiogram	O
+(	O
+ECG	O
+)	O
+.	O
+
+Paleoceanographic	O
+data	O
+from	O
+the	O
+Laurentian	O
+Fan	O
+,	O
+used	O
+as	O
+a	O
+proxy	O
+for	O
+sea	O
+surface	O
+temperature	O
+,	O
+reveal	O
+that	O
+surface	O
+slope	O
+waters	O
+north	O
+of	O
+the	O
+Gulf	O
+Stream	O
+experienced	O
+warming	O
+during	O
+the	O
+Little	O
+Ice	O
+Age	O
+of	O
+the	O
+16th	O
+to	O
+19th	O
+centuries	O
+and	O
+support	O
+the	O
+notion	O
+of	O
+an	O
+NAO	O
+-	O
+driven	O
+coupled	O
+system	O
+.	O
+
+This	O
+effect	O
+required	O
+(	O
+i	O
+)	O
+IR	B-GENE
+activation	O
+since	O
+it	O
+was	O
+abrogated	O
+by	O
+IR	B-GENE
+mutation	O
+at	O
+tyrosines	O
+1162	O
+and	O
+1163	O
+and	O
+(	O
+ii	O
+)	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activation	O
+since	O
+it	O
+was	O
+abolished	O
+by	O
+overexpression	O
+of	O
+dominant	B-GENE
+-	I-GENE
+negative	I-GENE
+IkappaB	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	I-GENE
+A32	I-GENE
+/	I-GENE
+36	I-GENE
+)	I-GENE
+and	O
+mimicked	O
+by	O
+overexpression	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+c	B-GENE
+-	I-GENE
+Rel	I-GENE
+subunit	I-GENE
+.	O
+
+The	O
+factor	O
+designated	O
+B	O
+formed	O
+a	O
+complex	O
+centered	O
+on	O
+the	O
+sequence	O
+TGTGGT	O
+,	O
+a	O
+core	O
+motif	O
+recognized	O
+by	O
+members	O
+of	O
+the	O
+AML	B-GENE
+/	I-GENE
+CBFalpha	I-GENE
+transcription	I-GENE
+factor	I-GENE
+family	I-GENE
+.	O
+
+Furthermore	O
+,	O
+overexpression	O
+of	O
+AML3	B-GENE
+/	O
+CBFalpha1	B-GENE
+could	O
+rescue	O
+the	O
+AML1	B-GENE
+-	O
+ETO	B-GENE
+repression	O
+.	O
+
+We	O
+examined	O
+Akt	B-GENE
+activation	O
+in	O
+Lyn	B-GENE
+-	O
+,	O
+Syk	B-GENE
+-	O
+and	O
+Btk	B-GENE
+-	O
+deficient	O
+DT40	O
+cells	O
+and	O
+B	O
+cells	O
+from	O
+Lyn	B-GENE
+(	I-GENE
+-	I-GENE
+/	I-GENE
+-	I-GENE
+)	I-GENE
+mice	O
+.	O
+
+Regulators	O
+of	O
+G	B-GENE
+protein	I-GENE
+signaling	I-GENE
+(	I-GENE
+RGS	I-GENE
+)	I-GENE
+proteins	I-GENE
+that	O
+contain	O
+DEP	B-GENE
+(	O
+disheveled	B-GENE
+,	O
+EGL	B-GENE
+-	I-GENE
+10	I-GENE
+,	O
+pleckstrin	B-GENE
+)	O
+and	O
+GGL	B-GENE
+(	O
+G	B-GENE
+protein	I-GENE
+gamma	I-GENE
+subunit	I-GENE
+-	I-GENE
+like	I-GENE
+)	O
+domains	O
+form	O
+a	O
+subfamily	O
+that	O
+includes	O
+the	O
+mammalian	B-GENE
+RGS	I-GENE
+proteins	I-GENE
+RGS6	B-GENE
+,	O
+RGS7	B-GENE
+,	O
+RGS9	B-GENE
+,	O
+and	O
+RGS11	B-GENE
+.	O
+
+Cloning	O
+and	O
+expression	O
+of	O
+a	O
+specific	O
+human	B-GENE
+alpha	I-GENE
+1	I-GENE
+,	I-GENE
+2	I-GENE
+-	I-GENE
+mannosidase	I-GENE
+that	O
+trims	O
+Man9GlcNAc2	O
+to	O
+Man8GlcNAc2	O
+isomer	O
+B	O
+during	O
+N	O
+-	O
+glycan	O
+biosynthesis	O
+.	O
+
+The	O
+ORs	O
+of	O
+GC	O
+,	O
+adjusted	O
+for	O
+age	O
+and	O
+sex	O
+,	O
+varied	O
+from	O
+17	O
+.	O
+1	O
+,	O
+for	O
+those	O
+with	O
+baseline	O
+diagnoses	O
+of	O
+superficial	O
+intestinal	O
+metaplasia	O
+(	O
+IM	O
+)	O
+,	O
+to	O
+29	O
+.	O
+3	O
+,	O
+for	O
+those	O
+with	O
+deep	O
+IM	O
+or	O
+mild	O
+dysplasia	O
+(	O
+DYS	O
+)	O
+or	O
+IM	O
+with	O
+glandular	O
+atrophy	O
+and	O
+neck	O
+hyperplasia	O
+,	O
+to	O
+104	O
+.	O
+2	O
+,	O
+for	O
+those	O
+with	O
+moderate	O
+or	O
+severe	O
+DYS	O
+,	O
+as	O
+compared	O
+with	O
+subjects	O
+with	O
+superficial	O
+gastritis	O
+(	O
+SG	O
+)	O
+or	O
+chronic	O
+atrophic	O
+gastritis	O
+(	O
+CAG	O
+)	O
+at	O
+baseline	O
+.	O
+
+Here	O
+we	O
+report	O
+that	O
+Dbp5p	B-GENE
+and	O
+Rat7p	B-GENE
+interact	O
+through	O
+their	O
+Nterminal	O
+domains	O
+.	O
+
+Thus	O
+,	O
+the	O
+nematode	O
+genes	O
+could	O
+be	O
+the	O
+homologs	B-GENE
+of	I-GENE
+Hh	I-GENE
+molecules	I-GENE
+in	O
+other	O
+phyla	O
+.	O
+
+A	O
+subset	O
+of	O
+mutations	O
+in	O
+the	O
+Psi	B-GENE
+synthase	I-GENE
+domain	I-GENE
+impairs	O
+association	O
+of	O
+the	O
+altered	O
+Cbf5p	B-GENE
+proteins	I-GENE
+with	O
+selected	O
+box	O
+H	B-GENE
+/	I-GENE
+ACA	I-GENE
+snoRNAs	I-GENE
+,	O
+suggesting	O
+that	O
+the	O
+functional	O
+catalytic	O
+domain	O
+is	O
+essential	O
+for	O
+that	O
+interaction	O
+.	O
+
+The	O
+transcription	B-GENE
+factor	I-GENE
+CHOP	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+homologous	I-GENE
+protein	I-GENE
+10	I-GENE
+)	O
+is	O
+a	O
+bZIP	B-GENE
+protein	I-GENE
+induced	O
+by	O
+a	O
+variety	O
+of	O
+stimuli	O
+that	O
+evoke	O
+cellular	O
+stress	O
+responses	O
+and	O
+has	O
+been	O
+shown	O
+to	O
+arrest	O
+cell	O
+growth	O
+and	O
+to	O
+promote	O
+programmed	O
+cell	O
+death	O
+.	O
+
+Thus	O
+,	O
+CHOP	B-GENE
+not	O
+only	O
+is	O
+a	O
+negative	O
+or	O
+a	O
+positive	O
+regulator	O
+of	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+target	O
+genes	O
+but	O
+also	O
+,	O
+when	O
+tethered	O
+to	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+factors	I-GENE
+,	O
+can	O
+activate	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+target	O
+genes	O
+.	O
+
+This	O
+motif	O
+,	O
+first	O
+described	O
+for	O
+the	O
+Drosophila	B-GENE
+homeobox	I-GENE
+activator	I-GENE
+DEAF	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+identifies	O
+an	O
+emerging	O
+group	O
+of	O
+metazoan	O
+transcriptional	O
+modulators	O
+.	O
+
+RNase	B-GENE
+MRP	I-GENE
+is	O
+a	O
+ribonucleoprotein	O
+endoribonuclease	O
+that	O
+has	O
+been	O
+shown	O
+to	O
+have	O
+roles	O
+in	O
+both	O
+mitochondrial	O
+DNA	O
+replication	O
+and	O
+nuclear	B-GENE
+5	I-GENE
+.	I-GENE
+8S	I-GENE
+rRNA	I-GENE
+processing	O
+.	O
+
+We	O
+have	O
+examined	O
+the	O
+regulation	O
+of	O
+the	O
+FGFR	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+(	O
+cek	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+in	O
+avian	O
+myogenic	O
+cultures	O
+by	O
+immunocytochemistry	O
+and	O
+Northern	O
+blot	O
+analysis	O
+.	O
+
+Regulation	O
+of	O
+avian	B-GENE
+fibroblast	I-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+1	I-GENE
+(	O
+FGFR	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+gene	O
+expression	O
+during	O
+skeletal	O
+muscle	O
+differentiation	O
+.	O
+
+The	O
+backbone	O
+dynamics	O
+of	O
+residues	O
+located	O
+in	O
+the	O
+folded	O
+part	O
+of	O
+CRP2	B-GENE
+(	O
+LIM2	B-GENE
+)	O
+R122A	B-GENE
+have	O
+been	O
+characterized	O
+by	O
+proton	O
+-	O
+detected	O
+(	O
+15	O
+)	O
+N	O
+NMR	O
+spectroscopy	O
+.	O
+
+Rac	B-GENE
+causes	O
+uncapping	O
+of	O
+actin	B-GENE
+filaments	I-GENE
+(	O
+F	B-GENE
+-	I-GENE
+actin	I-GENE
+)	O
+at	O
+the	O
+plus	O
+-	O
+ends	O
+,	O
+through	O
+phosphatidylinositol	O
+4	O
+,	O
+5	O
+bisphosphate	O
+(	O
+PIP2	O
+)	O
+,	O
+and	O
+eventually	O
+induces	O
+membrane	O
+ruffling	O
+.	O
+
+However	O
+,	O
+a	O
+specific	O
+ICE	B-GENE
+/	O
+caspase	B-GENE
+-	I-GENE
+1	I-GENE
+inhibitor	O
+called	O
+N1445	O
+completely	O
+abolished	O
+the	O
+CK	B-GENE
+-	O
+induced	O
+apoptosis	O
+by	O
+reactivating	O
+PKB	B-GENE
+,	O
+but	O
+without	O
+affecting	O
+the	O
+CK	B-GENE
+-	O
+induced	O
+suppression	O
+of	O
+Ras	B-GENE
+transformation	O
+.	O
+
+OBJECTIVE	O
+:	O
+Although	O
+the	O
+preponderance	O
+of	O
+findings	O
+offer	O
+support	O
+for	O
+transient	O
+(	O
+where	O
+is	O
+it	O
+?	O
+)	O
+as	O
+opposed	O
+to	O
+sustained	O
+(	O
+what	O
+is	O
+it	O
+?	O
+)	O
+deficit	O
+,	O
+a	O
+need	O
+remains	O
+for	O
+specific	O
+depiction	O
+of	O
+the	O
+deficit	O
+.	O
+
+The	O
+AL	O
+-	O
+R8	O
+SI	O
+:	O
+the	O
+next	O
+generation	O
+staging	O
+container	O
+for	O
+plutonium	O
+pits	O
+at	O
+the	O
+USDOE	O
+Pantex	O
+Plant	O
+.	O
+
+One	O
+form	O
+of	O
+the	O
+SBEI	B-GENE
+gene	I-GENE
+transcript	I-GENE
+in	O
+12	O
+-	O
+day	O
+old	O
+kernels	O
+contained	O
+the	O
+exon	O
+I	O
++	O
+II	O
++	O
+III	O
+combination	O
+at	O
+the	O
+5	O
+'	O
+end	O
+,	O
+whereas	O
+other	O
+forms	O
+differed	O
+by	O
+inclusion	O
+of	O
+intron	O
+1	O
+or	O
+exclusion	O
+of	O
+exon	O
+II	O
+sequences	O
+.	O
+
+In	O
+PC	O
+,	O
+rare	O
+MNGCs	O
+had	O
+intranuclear	O
+inclusions	O
+and	O
+grooves	O
+.	O
+
+16	O
+percent	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+and	O
+sustained	O
+normalization	O
+of	O
+serum	B-GENE
+alanine	I-GENE
+aminotransferase	I-GENE
+levels	O
+(	O
+41	O
+percent	O
+vs	O
+.	O
+
+Its	O
+C	O
+-	O
+terminal	O
+catalytic	O
+domain	O
+was	O
+found	O
+to	O
+be	O
+highly	O
+conserved	O
+in	O
+the	O
+homologues	O
+p140	B-GENE
+(	O
+ras	B-GENE
+-	O
+GRF	B-GENE
+)	O
+and	O
+Sos	B-GENE
+.	O
+
+356	O
+,	O
+93	O
+-	O
+98	O
+]	O
+.	O
+
+In	O
+assays	O
+with	O
+purified	O
+enzymes	O
+,	O
+wild	O
+-	O
+type	O
+but	O
+not	O
+PTPS	B-GENE
+-	O
+S19A	B-GENE
+was	O
+a	O
+specific	O
+substrate	O
+for	O
+the	O
+cGMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	I-GENE
+cGK	I-GENE
+)	I-GENE
+type	I-GENE
+I	I-GENE
+and	I-GENE
+II	I-GENE
+.	O
+
+R	O
+.	O
+,	O
+Fleischmann	O
+,	O
+R	O
+.	O
+,	O
+Venter	O
+,	O
+J	O
+.	O
+
+The	O
+N	O
+-	O
+terminal	O
+domain	O
+of	O
+approximately	O
+70	O
+kDa	O
+exhibits	O
+11	O
+imperfect	O
+amino	O
+acid	O
+repeats	O
+that	O
+show	O
+some	O
+homology	O
+to	O
+promastigote	O
+surface	O
+glycoproteins	O
+of	O
+the	O
+psa2	B-GENE
+/	O
+gp46	B-GENE
+complex	O
+.	O
+
+In	O
+contrast	O
+to	O
+previously	O
+characterized	O
+proteophosphoglycans	O
+,	O
+the	O
+ppg1	B-GENE
+gene	O
+product	O
+is	O
+predominantly	O
+membrane	O
+-	O
+associated	O
+and	O
+it	O
+is	O
+expressed	O
+on	O
+the	O
+promastigote	O
+cell	O
+surface	O
+.	O
+
+Most	O
+important	O
+,	O
+infection	O
+of	O
+the	O
+cells	O
+with	O
+an	O
+adenoviral	O
+construct	O
+expressing	O
+this	O
+mutant	O
+inhibited	O
+the	O
+induction	O
+of	O
+VEGF	B-GENE
+mRNA	I-GENE
+under	O
+conditions	O
+that	O
+mimic	O
+hypoxia	O
+.	O
+
+Neuregulin	B-GENE
+stimulates	O
+ErbB2	B-GENE
+,	O
+ErbB3	B-GENE
+,	O
+and	O
+ErbB4	B-GENE
+,	O
+members	O
+of	O
+the	O
+ErbB	B-GENE
+family	I-GENE
+of	O
+receptor	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+Anu2p	B-GENE
+is	O
+the	O
+yeast	B-GENE
+homologue	I-GENE
+of	I-GENE
+mammalian	I-GENE
+epsilon	I-GENE
+-	I-GENE
+COP	I-GENE
+and	O
+the	O
+abrupt	O
+accumulation	O
+of	O
+the	O
+ER	O
+membrane	O
+caused	O
+by	O
+a	O
+blockage	O
+of	O
+the	O
+early	O
+protein	O
+transport	O
+pathway	O
+leads	O
+to	O
+alteration	O
+of	O
+nuclear	O
+morphology	O
+of	O
+the	O
+budding	O
+yeast	O
+cells	O
+.	O
+
+In	O
+PC12	O
+cells	O
+,	O
+nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+induces	O
+neuronal	O
+differentiation	O
+and	O
+repressed	O
+expression	O
+of	O
+nrg	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+a	O
+PC12	O
+cell	O
+mutant	O
+that	O
+is	O
+deficient	O
+in	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+activity	O
+(	O
+AB	O
+.	O
+11	O
+)	O
+,	O
+all	O
+three	O
+differentiating	O
+agents	O
+were	O
+unable	O
+to	O
+down	O
+-	O
+regulate	O
+nrg	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+.	O
+
+TSC1	B-GENE
+mutations	I-GENE
+include	O
+two	O
+nonsense	O
+mutations	O
+,	O
+four	O
+insertions	O
+,	O
+and	O
+three	O
+splice	O
+mutations	O
+.	O
+
+Twelve	O
+patients	O
+without	O
+abnormalities	O
+in	O
+the	O
+PTT	O
+are	O
+assumed	O
+to	O
+harbor	O
+missense	O
+mutations	O
+,	O
+probably	O
+in	O
+TSC2	B-GENE
+.	O
+
+The	O
+first	O
+algorithm	O
+,	O
+FOREPROJ	O
+,	O
+is	O
+a	O
+fast	O
+-	O
+forward	O
+projection	O
+algorithm	O
+that	O
+allows	O
+calculation	O
+of	O
+the	O
+3	O
+-	O
+D	O
+attenuation	O
+correction	O
+factors	O
+(	O
+ACF	O
+'	O
+s	O
+)	O
+directly	O
+from	O
+a	O
+two	O
+-	O
+dimensional	O
+(	O
+2	O
+-	O
+D	O
+)	O
+transmission	O
+scan	O
+,	O
+without	O
+first	O
+reconstructing	O
+the	O
+attenuation	O
+map	O
+and	O
+then	O
+performing	O
+a	O
+3	O
+-	O
+D	O
+forward	O
+projection	O
+.	O
+
+The	O
+RMR	O
+was	O
+measured	O
+twice	O
+in	O
+each	O
+phase	O
+and	O
+found	O
+to	O
+be	O
+similar	O
+(	O
+F	O
+(	O
+1	O
+,	O
+18	O
+)	O
+=	O
+0	O
+.	O
+863	O
+)	O
+across	O
+the	O
+follicular	O
+(	O
+5018	O
+kJ	O
+/	O
+24	O
+h	O
+)	O
+and	O
+the	O
+luteal	O
+(	O
+5098	O
+kJ	O
+/	O
+24	O
+h	O
+)	O
+phases	O
+.	O
+
+In	O
+gel	O
+mobility	O
+shift	O
+assays	O
+,	O
+we	O
+found	O
+no	O
+evidence	O
+for	O
+VDR	B-GENE
+-	O
+TR	B-GENE
+heterodimer	O
+interaction	O
+with	O
+any	O
+tested	O
+element	O
+.	O
+
+The	O
+relative	O
+importance	O
+of	O
+these	O
+two	O
+mechanisms	O
+differed	O
+in	O
+a	O
+response	O
+element	O
+-	O
+specific	O
+manner	O
+.	O
+
+After	O
+14	O
+d	O
+of	O
+overfeeding	O
+,	O
+hepatic	O
+PL	O
+profiles	O
+were	O
+identical	O
+in	O
+the	O
+two	O
+breeds	O
+and	O
+similar	O
+to	O
+that	O
+in	O
+control	O
+livers	O
+;	O
+choline	O
+-	O
+containing	O
+PL	O
+accounted	O
+for	O
+95	O
+%	O
+of	O
+total	O
+PL	O
+.	O
+
+C	O
+-	O
+SP	O
+duration	O
+was	O
+significantly	O
+reduced	O
+in	O
+ALS	O
+patients	O
+compared	O
+to	O
+controls	O
+at	O
+low	O
+stimulation	O
+intensity	O
+corresponding	O
+to	O
+an	O
+MEP	O
+threshold	O
+increased	O
+by	O
+15	O
+%	O
+.	O
+
+These	O
+data	O
+show	O
+that	O
+the	O
+spv	B-GENE
+virulence	I-GENE
+genes	I-GENE
+belong	O
+simultaneously	O
+to	O
+several	O
+regulons	O
+in	O
+the	O
+cell	O
+,	O
+raising	O
+the	O
+possibility	O
+that	O
+spv	B-GENE
+expression	O
+can	O
+be	O
+fine	O
+-	O
+tuned	O
+in	O
+response	O
+to	O
+multiple	O
+environmental	O
+inputs	O
+.	O
+
+Intensive	O
+synthesis	O
+of	O
+PNA	B-GENE
+in	O
+the	O
+cells	O
+of	O
+microvascular	O
+wall	O
+evidenced	O
+of	O
+their	O
+high	O
+functional	O
+activity	O
+,	O
+and	O
+the	O
+synthesis	O
+of	O
+DNA	O
+in	O
+them	O
+showed	O
+their	O
+ability	O
+for	O
+proliferation	O
+,	O
+i	O
+.	O
+g	O
+.	O
+-	O
+-	O
+for	O
+growth	O
+.	O
+
+Tracheal	O
+transsection	O
+combined	O
+with	O
+hilar	O
+ligation	O
+(	O
+TL	O
+&	O
+PL	O
+)	O
+effected	O
+a	O
+reduction	O
+of	O
+19	O
+.	O
+9	O
+%	O
+(	O
+n	O
+.	O
+s	O
+.	O
+)	O
+.	O
+
+Kinase	O
+-	O
+deficient	O
+erbB	B-GENE
+proteins	I-GENE
+reduced	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+EGF	B-GENE
+)	O
+-	O
+induced	O
+tyrosine	O
+phosphorylation	O
+of	O
+endogenous	O
+Shc	B-GENE
+proteins	I-GENE
+and	O
+also	O
+reduced	O
+immediate	O
+and	O
+sustained	O
+EGF	B-GENE
+-	I-GENE
+induced	I-GENE
+ERK	I-GENE
+MAPK	I-GENE
+activities	O
+in	O
+human	O
+glioblastoma	O
+cells	O
+,	O
+although	O
+basal	O
+ERK	B-GENE
+MAPK	I-GENE
+activities	O
+were	O
+unaffected	O
+.	O
+
+Using	O
+immunolocalization	O
+,	O
+we	O
+observe	O
+that	O
+ACE3	B-GENE
+,	O
+a	O
+440	O
+-	O
+bp	O
+chorion	O
+element	O
+that	O
+contains	O
+information	O
+sufficient	O
+to	O
+drive	O
+amplification	O
+,	O
+directs	O
+DmORC	B-GENE
+localization	O
+in	O
+follicle	O
+cells	O
+.	O
+
+Therefore	O
+,	O
+homozygous	O
+co	O
+-	O
+deletions	O
+of	O
+CDKN2A	B-GENE
+and	O
+CDKN2B	B-GENE
+rather	O
+than	O
+mutations	O
+targeting	O
+individual	O
+transcripts	O
+are	O
+frequently	O
+selected	O
+for	O
+in	O
+these	O
+tumors	O
+.	O
+
+Here	O
+,	O
+we	O
+show	O
+that	O
+aortic	O
+explants	O
+isolated	O
+from	O
+PPARalpha	B-GENE
+-	O
+null	O
+mice	O
+display	O
+an	O
+exacerbated	O
+response	O
+to	O
+inflammatory	O
+stimuli	O
+,	O
+such	O
+as	O
+lipopolysaccharide	O
+(	O
+LPS	O
+)	O
+,	O
+as	O
+demonstrated	O
+by	O
+increased	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+secretion	O
+.	O
+
+Albumin	O
+expression	O
+is	O
+maintained	O
+in	O
+the	O
+liver	O
+by	O
+a	O
+combination	O
+of	O
+liver	O
+-	O
+enriched	O
+transcription	O
+factors	O
+such	O
+as	O
+CAAT	B-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	I-GENE
+C	I-GENE
+/	I-GENE
+EBP	I-GENE
+)	I-GENE
+alpha	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+.	O
+
+The	O
+requirement	O
+for	O
+proteolytic	O
+activity	O
+of	O
+both	O
+FVIIa	B-GENE
+and	O
+FXa	B-GENE
+suggests	O
+that	O
+protease	O
+-	O
+activated	O
+receptors	O
+may	O
+be	O
+involved	O
+.	O
+
+Amyloid	B-GENE
+beta	I-GENE
+-	I-GENE
+protein	I-GENE
+(	O
+Abeta	B-GENE
+)	O
+is	O
+the	O
+main	O
+constituent	O
+of	O
+amyloid	O
+fibrils	O
+found	O
+in	O
+senile	O
+plaques	O
+and	O
+cerebral	O
+vessels	O
+in	O
+Alzheimer	O
+'	O
+s	O
+disease	O
+(	O
+AD	O
+)	O
+and	O
+is	O
+derived	O
+by	O
+proteolysis	O
+from	O
+the	O
+beta	B-GENE
+-	I-GENE
+amyloid	I-GENE
+precursor	I-GENE
+protein	I-GENE
+(	O
+APP	B-GENE
+)	O
+.	O
+
+The	O
+importin	B-GENE
+alpha	I-GENE
+.	I-GENE
+beta	I-GENE
+heterodimer	I-GENE
+mediates	O
+nuclear	O
+import	O
+of	O
+proteins	O
+containing	O
+classical	O
+nuclear	O
+localization	O
+signals	O
+.	O
+
+The	O
+expressed	O
+G1	B-GENE
+-	O
+G2	B-GENE
+bound	O
+to	O
+both	O
+hyaluronan	O
+and	O
+link	B-GENE
+protein	I-GENE
+indicating	O
+that	O
+the	O
+immunoglobulin	B-GENE
+-	I-GENE
+fold	I-GENE
+motif	I-GENE
+and	O
+proteoglycan	O
+tandem	O
+repeat	O
+loops	O
+of	O
+the	O
+G1	B-GENE
+domain	I-GENE
+were	O
+correctly	O
+folded	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+the	O
+presence	O
+or	O
+absence	O
+per	O
+se	O
+of	O
+keratan	O
+sulfate	O
+on	O
+native	O
+G1	O
+-	O
+G2	O
+does	O
+not	O
+affect	O
+the	O
+activity	O
+of	O
+atrolysin	O
+C	O
+toward	O
+the	O
+two	O
+sites	O
+.	O
+
+Despite	O
+i	O
+.	O
+v	O
+.	O
+steroid	O
+therapy	O
+,	O
+[	O
+NOexh	O
+]	O
+remained	O
+elevated	O
+throughout	O
+recovery	O
+(	O
+37	O
+.	O
+9	O
++	O
+/	O
+-	O
+4	O
+.	O
+8	O
+ppb	O
+,	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+until	O
+discharge	O
+(	O
+40	O
+.	O
+9	O
++	O
+/	O
+-	O
+4	O
+.	O
+3	O
+ppb	O
+,	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+It	O
+contains	O
+binding	O
+sites	O
+for	O
+several	O
+transcription	O
+factors	O
+,	O
+for	O
+example	O
+:	O
+(	O
+i	O
+)	O
+a	O
+well	O
+-	O
+characterized	O
+binding	O
+site	O
+for	O
+rel	B-GENE
+/	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+transcription	O
+factors	O
+in	O
+its	O
+3	O
+'	O
+-	O
+end	O
+(	O
+the	O
+H2TF1	B-GENE
+or	O
+kappaB1	B-GENE
+element	I-GENE
+)	O
+,	O
+(	O
+ii	O
+)	O
+a	O
+second	O
+kappaB	B-GENE
+site	I-GENE
+(	O
+the	O
+kappaB2	B-GENE
+element	I-GENE
+)	O
+,	O
+which	O
+is	O
+located	O
+immediately	O
+adjacent	O
+5	O
+'	O
+to	O
+the	O
+H2TF1	B-GENE
+element	I-GENE
+and	O
+which	O
+is	O
+recognized	O
+by	O
+p65	B-GENE
+/	O
+relA	B-GENE
+in	O
+the	O
+human	B-GENE
+HLA	I-GENE
+system	O
+,	O
+and	O
+(	O
+iii	O
+)	O
+an	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+ATF	B-GENE
+recognition	O
+sequence	O
+in	O
+the	O
+5	O
+'	O
+end	O
+(	O
+EnA	B-GENE
+-	I-GENE
+TRE	I-GENE
+)	O
+.	O
+
+The	O
+tumorigenic	O
+E1A	B-GENE
++	O
+cHa	B-GENE
+-	I-GENE
+ras	I-GENE
+cells	O
+are	O
+characterized	O
+by	O
+high	O
+and	O
+constitutive	O
+DNA	O
+binding	O
+activities	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+in	O
+contrast	O
+to	O
+nontransformed	O
+cells	O
+and	O
+the	O
+E1A	B-GENE
+cells	O
+.	O
+
+The	O
+yeast	O
+C	B-GENE
+-	I-GENE
+type	I-GENE
+cyclin	I-GENE
+Ume3p	B-GENE
+/	O
+Srb11p	B-GENE
+and	O
+its	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+(	O
+Cdk	B-GENE
+)	O
+Ume5p	B-GENE
+are	O
+required	O
+for	O
+the	O
+full	O
+repression	O
+of	O
+genes	O
+involved	O
+in	O
+the	O
+stress	O
+response	O
+or	O
+meiosis	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+S1	B-GENE
+'	I-GENE
+specificity	I-GENE
+site	I-GENE
+is	O
+a	O
+deep	O
+and	O
+highly	O
+hydrophobic	O
+cavity	O
+.	O
+
+FZD4	B-GENE
+is	O
+homologous	O
+to	O
+FZD9	B-GENE
+and	O
+FZD10	B-GENE
+,	O
+and	O
+overall	O
+amino	O
+acid	O
+identity	O
+is	O
+as	O
+follows	O
+:	O
+FZD4	B-GENE
+vs	O
+FZD9	B-GENE
+,	O
+51	O
+.	O
+6	O
+%	O
+;	O
+FZD4	B-GENE
+vs	O
+FZD10	B-GENE
+,	O
+51	O
+.	O
+2	O
+%	O
+;	O
+FZD9	B-GENE
+vs	O
+FZD10	B-GENE
+,	O
+65	O
+.	O
+7	O
+%	O
+.	O
+
+The	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+responsive	O
+reporter	O
+construct	O
+,	O
+(	B-GENE
+PRDII	I-GENE
+)	I-GENE
+(	I-GENE
+4	I-GENE
+)	I-GENE
+-	O
+CAT	B-GENE
+,	O
+was	O
+used	O
+to	O
+explore	O
+transcription	O
+resulting	O
+from	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activated	O
+by	O
+Tat	B-GENE
+.	O
+
+The	O
+RNA	O
+transcripts	O
+structurally	O
+equivalent	O
+to	O
+I	B-GENE
+(	I-GENE
+2	I-GENE
+)	I-GENE
+sgRNAs	I-GENE
+of	O
+TMV	B-GENE
+U1	I-GENE
+and	O
+crTMV	O
+,	O
+but	O
+containing	O
+a	O
+hairpin	O
+structure	O
+(	O
+H	O
+)	O
+immediately	O
+upstream	O
+of	O
+IRES	B-GENE
+(	I-GENE
+MP	I-GENE
+,	I-GENE
+75	I-GENE
+)	I-GENE
+(	I-GENE
+HIRES	I-GENE
+(	I-GENE
+MP	I-GENE
+)	I-GENE
+,	I-GENE
+(	I-GENE
+75	I-GENE
+)	I-GENE
+(	I-GENE
+CR	I-GENE
+)	I-GENE
+-	I-GENE
+MP	I-GENE
+-	I-GENE
+CP	I-GENE
+-	I-GENE
+3	I-GENE
+'	I-GENE
+UTR	I-GENE
+;	O
+HIRES	B-GENE
+(	I-GENE
+MP	I-GENE
+,	I-GENE
+75	I-GENE
+)	I-GENE
+(	I-GENE
+U1	I-GENE
+)	I-GENE
+-	I-GENE
+MP	I-GENE
+-	I-GENE
+CP	I-GENE
+-	I-GENE
+3	I-GENE
+'	I-GENE
+UTR	I-GENE
+)	O
+,	O
+were	O
+able	O
+to	O
+express	O
+the	O
+MP	B-GENE
+gene	I-GENE
+in	O
+vitro	O
+.	O
+
+EIAV	B-GENE
+LTR	I-GENE
+sequence	I-GENE
+variability	O
+is	O
+confined	O
+mostly	O
+to	O
+a	O
+small	O
+portion	O
+of	O
+the	O
+enhancer	O
+within	O
+the	O
+U3	O
+segment	O
+of	O
+the	O
+LTR	O
+.	O
+
+The	O
+core	O
+of	O
+this	O
+enhancer	O
+contains	O
+two	O
+evolutionarily	O
+conserved	O
+binding	O
+sites	O
+for	O
+the	O
+homeodomain	B-GENE
+protein	I-GENE
+Tinman	B-GENE
+(	O
+Tin	B-GENE
+)	O
+,	O
+expressed	O
+in	O
+developing	O
+cardiac	O
+,	O
+somatic	O
+,	O
+and	O
+visceral	O
+muscle	O
+lineages	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+striking	O
+ability	O
+of	O
+polyoma	B-GENE
+middle	I-GENE
+T	I-GENE
+antigens	I-GENE
+to	O
+promote	O
+retinoic	O
+acid	O
+-	O
+induced	O
+differentiation	O
+appears	O
+to	O
+utilize	O
+ERK	B-GENE
+,	O
+but	O
+not	O
+JNK	B-GENE
+/	O
+SPK	B-GENE
+or	O
+p38	B-GENE
+signaling	O
+.	O
+
+All	O
+loci	O
+have	O
+a	O
+similar	O
+organization	O
+,	O
+except	O
+for	O
+H1	B-GENE
+.	I-GENE
+8	I-GENE
+that	O
+harbors	O
+two	O
+TcP2beta	B-GENE
+genes	I-GENE
+arranged	O
+in	O
+tandem	O
+and	O
+separated	O
+by	O
+a	O
+short	O
+repetitive	O
+sequence	O
+,	O
+named	O
+SIRE	O
+(	O
+short	O
+interspersed	O
+repetitive	O
+element	O
+)	O
+,	O
+which	O
+is	O
+also	O
+found	O
+upstream	O
+of	O
+the	O
+first	O
+gene	O
+of	O
+the	O
+tandem	O
+and	O
+downstream	O
+of	O
+the	O
+second	O
+.	O
+
+A	O
+proportion	O
+of	O
+APC	B-GENE
+wild	O
+-	O
+type	O
+colon	O
+carcinomas	O
+and	O
+melanomas	O
+also	O
+contains	O
+constitutive	O
+nuclear	O
+Tcf	B-GENE
+-	I-GENE
+4	I-GENE
+/	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+complexes	O
+as	O
+a	O
+result	O
+of	O
+dominant	O
+mutations	O
+in	O
+the	O
+N	O
+terminus	O
+of	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+that	O
+render	O
+it	O
+insensitive	O
+to	O
+downregulation	O
+by	O
+APC	B-GENE
+,	O
+GSK3	B-GENE
+beta	I-GENE
+,	O
+and	O
+Axin	B-GENE
+/	O
+Conductin	B-GENE
+.	O
+
+Similar	O
+mechanisms	O
+leading	O
+to	O
+deregulation	O
+of	O
+Tcf	B-GENE
+target	I-GENE
+gene	I-GENE
+activity	O
+are	O
+likely	O
+to	O
+be	O
+involved	O
+in	O
+melanoma	O
+and	O
+other	O
+forms	O
+of	O
+cancer	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Immediately	O
+before	O
+radical	O
+prostatectomy	O
+,	O
+bone	O
+marrow	O
+aspirates	O
+from	O
+both	O
+sides	O
+of	O
+the	O
+iliac	O
+crest	O
+were	O
+taken	O
+from	O
+287	O
+patients	O
+.	O
+
+With	O
+regard	O
+to	O
+nonhematologic	O
+toxicities	O
+,	O
+diarrhea	O
+,	O
+infection	O
+and	O
+elevated	O
+serum	B-GENE
+alkaline	I-GENE
+phosphatase	I-GENE
+of	O
+grade	O
+3	O
+or	O
+over	O
+were	O
+observed	O
+in	O
+2	O
+%	O
+of	O
+cycles	O
+,	O
+but	O
+were	O
+tolerable	O
+and	O
+reversible	O
+.	O
+
+LHbeta	B-GENE
+is	O
+expressed	O
+in	O
+pituitary	O
+gonadotrope	O
+cells	O
+and	O
+CGbeta	B-GENE
+is	O
+expressed	O
+in	O
+placental	O
+trophoblast	O
+cells	O
+.	O
+
+Regulation	O
+of	O
+HIV	O
+-	O
+1	O
+transcription	O
+.	O
+
+Human	B-GENE
+LTBP	I-GENE
+-	I-GENE
+1	I-GENE
+is	O
+known	O
+to	O
+exist	O
+in	O
+different	O
+forms	O
+.	O
+
+In	O
+an	O
+earlier	O
+study	O
+(	O
+Kimura	O
+,	O
+Y	O
+.	O
+,	O
+Kurzydlowski	O
+,	O
+K	O
+.	O
+,	O
+Tada	O
+,	O
+M	O
+.	O
+,	O
+and	O
+MacLennan	O
+,	O
+D	O
+.	O
+
+It	O
+consists	O
+of	O
+2185	O
+amino	O
+acid	O
+residues	O
+encoded	O
+by	O
+a	O
+9	O
+-	O
+kilobase	O
+pair	O
+mRNA	O
+;	O
+several	O
+splice	O
+variants	O
+have	O
+been	O
+detected	O
+in	O
+human	O
+and	O
+rat	O
+cDNA	O
+libraries	O
+.	O
+
+Cyclic	B-GENE
+AMP	I-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+binding	O
+to	O
+A	B-GENE
+-	I-GENE
+kinase	I-GENE
+anchoring	O
+proteins	O
+in	O
+living	O
+cells	O
+by	O
+fluorescence	O
+resonance	O
+energy	O
+transfer	O
+of	O
+green	B-GENE
+fluorescent	I-GENE
+protein	I-GENE
+fusion	O
+proteins	O
+.	O
+
+Factor	B-GENE
+XI	I-GENE
+deficiency	O
+is	O
+a	O
+rare	O
+hereditary	O
+bleeding	O
+disorder	O
+affecting	O
+the	O
+intrinsic	O
+pathway	O
+.	O
+
+The	O
+Ishasha	O
+samples	O
+show	O
+a	O
+range	O
+encompassing	O
+three	O
+trophic	O
+levels	O
+.	O
+
+The	O
+more	O
+traditional	O
+SERMS	O
+,	O
+clomiphene	O
+citrate	O
+and	O
+tamoxifen	O
+,	O
+will	O
+be	O
+reviewed	O
+along	O
+with	O
+such	O
+modern	O
+drugs	O
+as	O
+raloxifene	O
+and	O
+faslodex	O
+,	O
+with	O
+emphasis	O
+upon	O
+their	O
+actions	O
+on	O
+breast	O
+,	O
+uterus	O
+,	O
+bone	O
+and	O
+lipids	O
+.	O
+
+Ti	O
+exhibited	O
+a	O
+feather	O
+-	O
+like	O
+morphology	O
+.	O
+
+This	O
+organization	O
+suggests	O
+that	O
+duplication	O
+events	O
+that	O
+have	O
+generated	O
+the	O
+primate	O
+FUT3	B-GENE
+-	O
+FUT5	B-GENE
+-	O
+FUT6	B-GENE
+cluster	O
+might	O
+have	O
+occurred	O
+through	O
+a	O
+long	O
+-	O
+interspersed	O
+-	O
+nuclear	O
+-	O
+element	O
+-	O
+based	O
+mechanism	O
+of	O
+unequal	O
+crossing	O
+over	O
+,	O
+as	O
+described	O
+for	O
+the	O
+globin	B-GENE
+cluster	I-GENE
+.	O
+
+S	O
+.	O
+,	O
+Kim	O
+,	O
+S	O
+.	O
+
+The	O
+cop	B-GENE
+region	I-GENE
+also	O
+harbors	O
+a	O
+region	O
+of	O
+plasmid	O
+incompatibility	O
+,	O
+inc	B-GENE
+,	O
+encompassing	O
+a	O
+stem	O
+-	O
+loop	O
+structure	O
+,	O
+the	O
+repA	B-GENE
+promoter	I-GENE
+,	O
+Prep	B-GENE
+,	O
+as	O
+well	O
+as	O
+two	O
+distinct	O
+RepA	B-GENE
+binding	I-GENE
+sites	I-GENE
+,	O
+BD	O
+-	O
+1	O
+and	O
+BD	O
+-	O
+2	O
+.	O
+
+WA	O
+constructs	O
+afforded	O
+relaxed	O
+and	O
+positive	O
+topoisomers	O
+,	O
+and	O
+cyclization	O
+kinetics	O
+indicated	O
+slow	O
+interconversion	O
+of	O
+precursors	O
+to	O
+the	O
+two	O
+topoisomers	O
+.	O
+
+The	O
+RFX	B-GENE
+protein	I-GENE
+family	I-GENE
+includes	O
+members	O
+from	O
+yeast	O
+to	O
+humans	O
+,	O
+which	O
+function	O
+in	O
+various	O
+biological	O
+systems	O
+,	O
+and	O
+share	O
+a	O
+DNA	O
+-	O
+binding	O
+domain	O
+and	O
+a	O
+conserved	O
+C	O
+-	O
+terminal	O
+region	O
+.	O
+
+Binding	O
+to	O
+sulphatides	O
+and	O
+the	O
+alpha	B-GENE
+-	I-GENE
+dystroglycan	I-GENE
+receptor	I-GENE
+was	O
+much	O
+stronger	O
+and	O
+required	O
+at	O
+least	O
+two	O
+LG	B-GENE
+modules	I-GENE
+.	O
+
+Here	O
+,	O
+we	O
+propose	O
+that	O
+an	O
+antagonistic	O
+,	O
+BMP	B-GENE
+/	O
+ALK2	B-GENE
+/	O
+Smad	B-GENE
+-	O
+mediated	O
+signaling	O
+pathway	O
+is	O
+active	O
+on	O
+the	O
+right	O
+side	O
+of	O
+the	O
+Xenopus	O
+embryo	O
+.	O
+
+Gentamicin	O
+given	O
+by	O
+DPI	O
+and	O
+SVN	O
+significantly	O
+decreased	O
+the	O
+sputum	O
+Psa	O
+density	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+by	O
+almost	O
+one	O
+order	O
+of	O
+magnitude	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+largest	O
+value	O
+of	O
+the	O
+joint	O
+space	O
+may	O
+be	O
+used	O
+when	O
+evaluating	O
+rheumatoid	O
+AC	O
+joint	O
+space	O
+.	O
+
+An	O
+analysis	O
+of	O
+sequence	O
+of	O
+the	O
+mutant	B-GENE
+recN	I-GENE
+gene	I-GENE
+revealed	O
+a	O
+G	O
+:	O
+C	O
+to	O
+T	O
+:	O
+A	O
+transversion	O
+near	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+coding	O
+region	O
+.	O
+
+Nevertheless	O
+,	O
+in	O
+view	O
+of	O
+the	O
+potential	O
+transmission	O
+rates	O
+of	O
+HGV	O
+and	O
+the	O
+lack	O
+of	O
+effective	O
+immunization	O
+,	O
+HGV	O
+should	O
+be	O
+regarded	O
+as	O
+a	O
+potential	O
+occupational	O
+hazard	O
+for	O
+medical	O
+and	O
+dental	O
+staff	O
+.	O
+
+We	O
+have	O
+previously	O
+identified	O
+mouse	B-GENE
+and	I-GENE
+human	I-GENE
+cDNAs	I-GENE
+encoding	I-GENE
+UNC	I-GENE
+-	I-GENE
+51	I-GENE
+-	I-GENE
+like	I-GENE
+kinase	I-GENE
+(	O
+ULK1	B-GENE
+)	O
+.	O
+
+ULKs	B-GENE
+and	O
+UNC	B-GENE
+-	I-GENE
+51	I-GENE
+share	O
+a	O
+typical	O
+domain	O
+structure	O
+of	O
+an	O
+amino	O
+-	O
+terminal	O
+kinase	O
+domain	O
+,	O
+a	O
+central	O
+proline	O
+/	O
+serine	O
+rich	O
+(	O
+PS	O
+)	O
+domain	O
+,	O
+and	O
+a	O
+carboxy	O
+-	O
+terminal	O
+(	O
+C	O
+)	O
+domain	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+ULK2	B-GENE
+is	O
+involved	O
+in	O
+a	O
+previously	O
+uncharacterized	O
+signaling	O
+pathway	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Connector	B-GENE
+enhancer	I-GENE
+of	I-GENE
+KSR	I-GENE
+(	O
+CNK	B-GENE
+)	O
+is	O
+a	O
+multidomain	O
+protein	O
+required	O
+for	O
+RAS	B-GENE
+signaling	O
+.	O
+
+In	O
+simpler	O
+organisms	O
+,	O
+the	O
+ATP	B-GENE
+sulfurylase	I-GENE
+and	O
+APS	B-GENE
+kinase	I-GENE
+reactions	O
+are	O
+catalyzed	O
+by	O
+separate	O
+enzymes	O
+encoded	O
+by	O
+two	O
+or	O
+three	O
+genes	O
+,	O
+suggesting	O
+that	O
+a	O
+fusion	O
+of	O
+separate	O
+genes	O
+during	O
+the	O
+course	O
+of	O
+evolution	O
+generated	O
+the	O
+bifunctional	O
+enzyme	O
+.	O
+
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+(	I-GENE
+EBV	I-GENE
+)	I-GENE
+latent	I-GENE
+membrane	I-GENE
+protein	I-GENE
+1	I-GENE
+(	O
+LMP1	B-GENE
+)	O
+is	O
+essential	O
+for	O
+EBV	O
+-	O
+mediated	O
+transformation	O
+of	O
+primary	O
+B	O
+lymphocytes	O
+.	O
+
+The	O
+amino	O
+-	O
+terminal	O
+half	O
+of	O
+1a	B-GENE
+is	O
+a	O
+distant	O
+homolog	B-GENE
+of	I-GENE
+alphavirus	I-GENE
+nonstructural	I-GENE
+protein	I-GENE
+nsP1	I-GENE
+,	O
+which	O
+has	O
+been	O
+implicated	O
+in	O
+capping	O
+viral	O
+RNAs	O
+.	O
+
+Moreover	O
+,	O
+a	O
+recombinant	O
+Ad	O
+expressing	O
+Ad5	B-GENE
+E4orf6	I-GENE
+/	I-GENE
+7	I-GENE
+induced	O
+apoptosis	O
+in	O
+rat	O
+cells	O
+when	O
+coinfected	O
+with	O
+wild	O
+-	O
+type	O
+p53	B-GENE
+-	O
+expressing	O
+Ad	O
+.	O
+
+CONCLUSION	O
+(	O
+S	O
+)	O
+:	O
+Measuring	O
+urinary	O
+LH	B-GENE
+levels	O
+is	O
+an	O
+excellent	O
+method	O
+for	O
+determining	O
+ovulation	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+evaluate	O
+the	O
+disease	O
+-	O
+free	O
+survival	O
+(	O
+DFS	O
+)	O
+and	O
+overall	O
+survival	O
+(	O
+OS	O
+)	O
+,	O
+prognostic	O
+factors	O
+,	O
+and	O
+treatment	O
+-	O
+related	O
+mortality	O
+of	O
+women	O
+with	O
+stage	O
+IIIB	O
+inflammatory	O
+breast	O
+cancer	O
+(	O
+IBC	O
+)	O
+treated	O
+with	O
+combined	O
+modality	O
+therapy	O
+(	O
+CMT	O
+)	O
+and	O
+high	O
+-	O
+dose	O
+chemotherapy	O
+(	O
+HDCT	O
+)	O
+with	O
+autologous	O
+stem	O
+-	O
+cell	O
+transplantation	O
+.	O
+
+We	O
+have	O
+cloned	O
+a	O
+novel	O
+100	O
+-	O
+kDa	O
+mammalian	O
+protein	O
+,	O
+which	O
+was	O
+recognized	O
+by	O
+an	O
+anti	O
+-	O
+peptide	O
+antibody	O
+against	O
+an	O
+epitope	O
+-	O
+containing	O
+nuclear	O
+localization	O
+signal	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+p65	B-GENE
+subunit	I-GENE
+.	O
+
+Insulin	B-GENE
+-	O
+regulated	O
+events	O
+,	O
+however	O
+,	O
+occur	O
+in	O
+all	O
+cells	O
+.	O
+
+Regulatory	O
+regions	O
+in	O
+the	O
+promoter	O
+and	O
+third	O
+intron	O
+of	O
+the	O
+growth	B-GENE
+hormone	I-GENE
+gene	I-GENE
+in	I-GENE
+rainbow	I-GENE
+trout	I-GENE
+,	O
+Oncorhynchus	O
+mykiss	O
+walbaum	O
+.	O
+
+Although	O
+most	O
+SFV	O
+genes	O
+have	O
+homologs	O
+encoded	O
+by	O
+other	O
+Chordopoxvirinae	O
+,	O
+the	O
+SFV	O
+genome	O
+lacks	O
+a	O
+key	O
+gene	O
+required	O
+for	O
+the	O
+production	O
+of	O
+extracellular	O
+enveloped	O
+virus	O
+.	O
+
+In	O
+addition	O
+,	O
+media	O
+containing	O
+F	B-GENE
+beta	I-GENE
+alpha	I-GENE
+/	O
+CG	B-GENE
+beta	I-GENE
+displayed	O
+high	O
+-	O
+affinity	O
+binding	O
+to	O
+both	O
+CG	B-GENE
+and	I-GENE
+FSH	I-GENE
+receptors	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+binding	O
+activity	O
+was	O
+significantly	O
+greater	O
+in	O
+T47D	O
+cells	O
+,	O
+and	O
+Western	O
+blots	O
+confirmed	O
+increased	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+protein	I-GENE
+levels	O
+in	O
+these	O
+cells	O
+.	O
+
+N	O
+.	O
+van	O
+Hoek	O
+,	O
+and	O
+M	O
+.	O
+
+Here	O
+,	O
+we	O
+describe	O
+a	O
+tyrosine	O
+-	O
+phosphorylated	O
+nuclear	O
+protein	O
+,	O
+YT521	B-GENE
+-	I-GENE
+B	I-GENE
+,	O
+and	O
+show	O
+that	O
+it	O
+interacts	O
+with	O
+the	O
+nuclear	B-GENE
+transcriptosomal	I-GENE
+component	I-GENE
+scaffold	I-GENE
+attachment	I-GENE
+factor	I-GENE
+B	I-GENE
+,	O
+and	O
+the	O
+68	B-GENE
+-	I-GENE
+kDa	I-GENE
+Src	I-GENE
+substrate	O
+associated	O
+during	O
+mitosis	O
+,	O
+Sam68	B-GENE
+.	O
+
+These	O
+mutants	O
+all	O
+failed	O
+to	O
+interact	O
+with	O
+the	O
+TraR	B-GENE
+fusion	I-GENE
+in	O
+the	O
+two	O
+-	O
+hybrid	O
+system	O
+.	O
+
+PhoP	B-GENE
+-	O
+PhoQ	B-GENE
+homologues	O
+in	O
+Pseudomonas	O
+aeruginosa	O
+regulate	O
+expression	O
+of	O
+the	O
+outer	B-GENE
+-	I-GENE
+membrane	I-GENE
+protein	I-GENE
+OprH	I-GENE
+and	O
+polymyxin	O
+B	O
+resistance	O
+.	O
+
+Deletion	O
+of	O
+fdsR	B-GENE
+revealed	O
+a	O
+dual	O
+regulatory	O
+effect	O
+of	O
+FdsR	B-GENE
+on	O
+the	O
+fds	B-GENE
+operon	I-GENE
+by	O
+acting	O
+as	O
+transcriptional	O
+activator	O
+in	O
+the	O
+presence	O
+of	O
+formate	O
+or	O
+as	O
+repressor	O
+in	O
+the	O
+absence	O
+of	O
+formate	O
+.	O
+
+With	O
+constructs	O
+containing	O
+the	O
+binding	O
+site	O
+of	O
+one	O
+gene	O
+fused	O
+to	O
+the	O
+promoter	O
+of	O
+the	O
+other	O
+,	O
+we	O
+demonstrated	O
+that	O
+the	O
+positional	O
+requirements	O
+are	O
+a	O
+function	O
+of	O
+the	O
+specific	O
+binding	O
+site	O
+,	O
+not	O
+the	O
+promoter	O
+.	O
+
+In	O
+addition	O
+,	O
+all	O
+three	O
+Opa	B-GENE
+proteins	I-GENE
+of	O
+C751	O
+bind	O
+equally	O
+well	O
+to	O
+HeLa	O
+cells	O
+transfected	O
+with	O
+cDNA	O
+encoding	O
+the	O
+carcinoembryonic	B-GENE
+antigen	I-GENE
+[	O
+CEA	B-GENE
+(	O
+CD66e	B-GENE
+)	O
+]	O
+subgroup	O
+of	O
+the	O
+CD66	B-GENE
+family	I-GENE
+,	O
+but	O
+show	O
+distinct	O
+tropism	O
+for	O
+CGM1	B-GENE
+-	O
+(	O
+CD66d	B-GENE
+)	O
+and	O
+NCA	B-GENE
+(	O
+CD66c	B-GENE
+)	O
+-	O
+expressing	O
+cells	O
+.	O
+
+The	O
+effect	O
+of	O
+smoking	O
+was	O
+not	O
+examined	O
+in	O
+this	O
+study	O
+,	O
+as	O
+such	O
+data	O
+were	O
+not	O
+available	O
+.	O
+
+BACKGROUND	O
+:	O
+Measurement	O
+of	O
+stereoacuity	O
+at	O
+varying	O
+distances	O
+,	O
+by	O
+real	O
+or	O
+simulated	O
+depth	O
+stereoacuity	O
+tests	O
+,	O
+is	O
+helpful	O
+in	O
+the	O
+evaluation	O
+of	O
+patients	O
+with	O
+binocular	O
+imbalance	O
+or	O
+strabismus	O
+.	O
+
+Additional	O
+studies	O
+revealed	O
+that	O
+bovine	B-GENE
+brain	I-GENE
+Galpha	I-GENE
+(	I-GENE
+q	I-GENE
+/	I-GENE
+11	I-GENE
+)	I-GENE
+could	O
+also	O
+bind	O
+to	O
+an	O
+N	O
+-	O
+terminal	O
+construct	O
+of	O
+GRK2	B-GENE
+,	O
+while	O
+no	O
+binding	O
+of	O
+Galpha	B-GENE
+(	I-GENE
+q	I-GENE
+/	I-GENE
+11	I-GENE
+)	I-GENE
+,	O
+Galpha	B-GENE
+(	I-GENE
+s	I-GENE
+)	I-GENE
+,	O
+Galpha	B-GENE
+(	I-GENE
+i	I-GENE
+)	I-GENE
+,	O
+or	O
+Galpha	B-GENE
+(	I-GENE
+12	I-GENE
+/	I-GENE
+13	I-GENE
+)	I-GENE
+to	O
+comparable	O
+constructs	O
+of	O
+GRK5	B-GENE
+or	O
+GRK6	B-GENE
+was	O
+observed	O
+.	O
+
+The	O
+elm1	B-GENE
+kinase	I-GENE
+functions	O
+in	O
+a	O
+mitotic	O
+signaling	O
+network	O
+in	O
+budding	O
+yeast	O
+.	O
+
+Reverse	O
+transcription	O
+(	O
+RT	O
+)	O
+-	O
+PCR	O
+products	O
+were	O
+synthesized	O
+with	O
+two	O
+degenerate	O
+primers	O
+derived	O
+from	O
+the	O
+conserved	O
+motifs	O
+of	O
+various	O
+tyrosine	B-GENE
+kinases	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+acetyltransferase	O
+activity	O
+of	O
+p300	B-GENE
+was	O
+observed	O
+to	O
+be	O
+distinct	O
+from	O
+the	O
+broadly	O
+essential	O
+activation	O
+function	O
+of	O
+the	O
+CH3	B-GENE
+domain	I-GENE
+/	O
+E1A	B-GENE
+-	O
+binding	O
+region	O
+.	O
+
+The	O
+proliferation	O
+-	O
+specific	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+/	O
+fork	B-GENE
+head	I-GENE
+homolog	I-GENE
+-	I-GENE
+11B	I-GENE
+protein	O
+(	O
+HFH	B-GENE
+-	I-GENE
+11B	I-GENE
+;	O
+also	O
+known	O
+as	O
+Trident	B-GENE
+and	O
+Win	B-GENE
+)	O
+is	O
+a	O
+family	O
+member	O
+of	O
+the	O
+winged	B-GENE
+helix	I-GENE
+/	O
+fork	B-GENE
+head	I-GENE
+transcription	O
+factors	O
+and	O
+in	O
+regenerating	O
+liver	O
+its	O
+expression	O
+is	O
+reactivated	O
+prior	O
+to	O
+hepatocyte	O
+entry	O
+into	O
+DNA	O
+replication	O
+(	O
+S	O
+phase	O
+)	O
+.	O
+
+In	O
+the	O
+mouse	O
+,	O
+CtBP1	B-GENE
+is	O
+expressed	O
+from	O
+embryo	O
+to	O
+adult	O
+,	O
+but	O
+CtBP2	B-GENE
+is	O
+mainly	O
+expressed	O
+during	O
+embryogenesis	O
+.	O
+
+The	O
+multiple	O
+functions	O
+of	O
+Pmt3p	B-GENE
+described	O
+here	O
+suggest	O
+that	O
+several	O
+nuclear	O
+proteins	O
+are	O
+regulated	O
+by	O
+Pmt3p	B-GENE
+conjugation	O
+.	O
+
+The	O
+role	O
+of	O
+transport	O
+by	O
+sea	O
+ice	O
+from	O
+the	O
+Kara	O
+Sea	O
+into	O
+the	O
+Arctic	O
+Ocean	O
+was	O
+assessed	O
+by	O
+a	O
+small	O
+subgroup	O
+at	O
+GEOMAR	O
+.	O
+
+We	O
+determined	O
+whether	O
+a	O
+single	O
+injection	O
+of	O
+slow	O
+-	O
+release	O
+estradiol	O
+-	O
+17beta	O
+(	O
+SRE2	O
+)	O
+would	O
+induce	O
+pseudopregnancy	O
+in	O
+gilts	O
+and	O
+whether	O
+PGF2alpha	O
+would	O
+regress	O
+the	O
+corpora	O
+lutea	O
+(	O
+CL	O
+)	O
+of	O
+pseudopregnancy	O
+.	O
+
+Among	O
+the	O
+remaining	O
+22	O
+sites	O
+,	O
+six	O
+are	O
+in	O
+the	O
+promoters	O
+of	O
+known	O
+alpha	O
+-	O
+specific	O
+genes	O
+and	O
+two	O
+other	O
+sites	O
+have	O
+an	O
+alpha2	B-GENE
+-	O
+Mcm1	B-GENE
+-	O
+dependent	O
+role	O
+in	O
+determining	O
+the	O
+direction	O
+of	O
+mating	O
+type	O
+switching	O
+.	O
+
+Activation	O
+of	O
+T	O
+cells	O
+via	O
+the	O
+TCR	B-GENE
+and	O
+other	O
+costimulatory	O
+receptors	O
+triggers	O
+a	O
+number	O
+of	O
+signaling	O
+cascades	O
+.	O
+
+A	O
+phylogenetic	O
+analysis	O
+with	O
+the	O
+TK	B-GENE
+domains	I-GENE
+from	O
+these	O
+sequences	O
+and	O
+a	O
+fourth	O
+,	O
+from	O
+a	O
+novel	O
+scavenger	B-GENE
+RTK	I-GENE
+(	O
+all	O
+domains	O
+comprise	O
+the	O
+signature	O
+for	O
+the	O
+TK	B-GENE
+class	I-GENE
+II	I-GENE
+receptors	I-GENE
+)	O
+,	O
+showed	O
+that	O
+they	O
+are	O
+distantly	O
+related	O
+to	O
+the	O
+insulin	B-GENE
+and	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+receptors	I-GENE
+.	O
+
+Results	O
+confirmed	O
+that	O
+stress	O
+produced	O
+CA3	O
+dendritic	O
+atrophy	O
+and	O
+tianeptine	O
+prevented	O
+it	O
+.	O
+
+We	O
+have	O
+isolated	O
+a	O
+binding	O
+partner	O
+for	O
+the	O
+Fanconi	B-GENE
+anemia	I-GENE
+group	I-GENE
+C	I-GENE
+protein	I-GENE
+(	O
+FANCC	B-GENE
+)	O
+by	O
+yeast	O
+two	O
+-	O
+hybrid	O
+screening	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+both	O
+transcription	O
+activators	O
+depend	O
+on	O
+or	O
+interact	O
+with	O
+different	O
+subunits	O
+of	O
+RNA	B-GENE
+polymerase	I-GENE
+,	O
+although	O
+their	O
+role	O
+in	O
+formation	O
+of	O
+proper	O
+DNA	O
+geometry	O
+may	O
+also	O
+be	O
+crucial	O
+.	O
+
+Klebsiella	O
+oxytoca	O
+can	O
+assimilate	O
+nitrate	O
+and	O
+nitrite	O
+by	O
+using	O
+enzymes	O
+encoded	O
+by	O
+the	O
+nasFEDCBA	B-GENE
+operon	I-GENE
+.	O
+
+Marked	O
+hemolysis	O
+significantly	O
+increased	O
+plasma	O
+values	O
+of	O
+potassium	O
+,	O
+phosphorus	O
+,	O
+total	O
+protein	O
+,	O
+and	O
+aspartate	B-GENE
+aminotransferase	I-GENE
+.	O
+
+Studies	O
+have	O
+substantiated	O
+the	O
+involvement	O
+of	O
+numerous	O
+loci	O
+on	O
+certain	O
+chromosomes	O
+;	O
+in	O
+excess	O
+of	O
+10	O
+chromosomes	O
+are	O
+thought	O
+to	O
+be	O
+involved	O
+.	O
+
+By	O
+negatively	O
+regulating	O
+GRK	B-GENE
+-	O
+mediated	O
+receptor	O
+phosphorylation	O
+,	O
+beta	B-GENE
+-	I-GENE
+arrestin	I-GENE
+-	O
+mediated	O
+processes	O
+such	O
+as	O
+Src	B-GENE
+recruitment	O
+and	O
+clathrin	B-GENE
+-	O
+mediated	O
+internalization	O
+,	O
+which	O
+are	O
+required	O
+for	O
+GPCR	B-GENE
+-	O
+mediated	O
+ERK	B-GENE
+activation	O
+,	O
+are	O
+inhibited	O
+,	O
+thus	O
+dampening	O
+further	O
+ERK	B-GENE
+activation	O
+.	O
+
+Based	O
+on	O
+subcellular	O
+fractionation	O
+,	O
+the	O
+47	B-GENE
+-	I-GENE
+kDa	I-GENE
+P	I-GENE
+-	I-GENE
+CIP2	I-GENE
+protein	I-GENE
+is	O
+mostly	O
+cytosolic	O
+.	O
+
+Supershift	O
+EMSAs	O
+identified	O
+that	O
+upstream	B-GENE
+stimulatory	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+and	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+USF	B-GENE
+-	I-GENE
+1	I-GENE
+and	I-GENE
+-	I-GENE
+2	I-GENE
+)	O
+were	O
+part	O
+of	O
+these	O
+complexes	O
+.	O
+
+Conversely	O
+,	O
+E1A	B-GENE
+binding	O
+to	O
+only	O
+p300	B-GENE
+/	O
+CBP	B-GENE
+results	O
+in	O
+an	O
+increase	O
+in	O
+PARP	B-GENE
+enzyme	I-GENE
+activity	O
+and	O
+consequently	O
+in	O
+cell	O
+death	O
+susceptibility	O
+to	O
+irradiation	O
+,	O
+which	O
+is	O
+effectively	O
+counteracted	O
+by	O
+the	O
+PARP	B-GENE
+chemical	O
+inhibitor	O
+3	O
+-	O
+aminobenzamide	O
+.	O
+
+These	O
+include	O
+the	O
+CACCC	O
+and	O
+CAAT	O
+motifs	O
+.	O
+
+Skin	O
+pH	O
+changes	O
+associated	O
+with	O
+iontophoresis	O
+.	O
+
+This	O
+distinction	O
+was	O
+based	O
+upon	O
+whether	O
+the	O
+diagnosis	O
+provided	O
+a	O
+straightforward	O
+range	O
+of	O
+prognoses	O
+or	O
+an	O
+ambiguous	O
+clinical	O
+implication	O
+.	O
+
+The	O
+availability	O
+of	O
+potent	O
+regulatory	O
+DNA	O
+cassettes	O
+harboring	O
+the	O
+murine	B-GENE
+D1A	I-GENE
+gene	I-GENE
+promoter	I-GENE
+could	O
+aid	O
+testing	O
+the	O
+neuronal	O
+-	O
+specific	O
+expression	O
+of	O
+transgenes	O
+in	O
+vivo	O
+.	O
+
+It	O
+may	O
+be	O
+dependent	O
+on	O
+location	O
+of	O
+a	O
+focus	O
+(	O
+according	O
+to	O
+EEG	O
+)	O
+as	O
+well	O
+as	O
+on	O
+the	O
+character	O
+and	O
+manifestation	O
+of	O
+the	O
+accompanying	O
+neuropsychologic	O
+symptomatology	O
+.	O
+
+The	O
+results	O
+of	O
+these	O
+studies	O
+demonstrate	O
+that	O
+the	O
+rat	O
+HDL	O
+receptor	O
+SR	B-GENE
+-	I-GENE
+BI	I-GENE
+promoter	O
+contains	O
+two	O
+sterol	O
+response	O
+elements	O
+(	O
+pSRE	O
+and	O
+dSRE	O
+)	O
+through	O
+which	O
+SREBP	B-GENE
+-	I-GENE
+1a	I-GENE
+can	O
+bind	O
+and	O
+activate	O
+transcription	O
+of	O
+this	O
+gene	O
+.	O
+
+Of	O
+these	O
+patients	O
+,	O
+46	O
+,	O
+164	O
+were	O
+placed	O
+on	O
+a	O
+waiting	O
+list	O
+for	O
+transplantation	O
+,	O
+23	O
+,	O
+275	O
+of	O
+whom	O
+received	O
+a	O
+first	O
+cadaveric	O
+transplant	O
+between	O
+1991	O
+and	O
+1997	O
+.	O
+
+In	O
+electrophoretic	O
+mobility	O
+shift	O
+assay	O
+(	O
+EMSA	O
+)	O
+,	O
+this	O
+GLUT4	B-GENE
+repressor	I-GENE
+element	I-GENE
+(	O
+G4RE	B-GENE
+)	O
+generated	O
+specific	O
+bands	O
+with	O
+nuclear	O
+extracts	O
+from	O
+preadipocytes	O
+,	O
+but	O
+not	O
+from	O
+adipocytes	O
+.	O
+
+Syndromes	O
+of	O
+abnormal	O
+fat	O
+redistribution	O
+and	O
+metabolic	O
+complications	O
+in	O
+HIV	O
+-	O
+infected	O
+patients	O
+.	O
+
+Cytoprotection	O
+with	O
+amifostine	O
+in	O
+radiotherapy	O
+or	O
+radio	O
+-	O
+chemotherapy	O
+of	O
+head	O
+and	O
+neck	O
+tumors	O
+
+Immunohistochemical	O
+staining	O
+was	O
+positive	O
+for	O
+S	B-GENE
+-	I-GENE
+100	I-GENE
+in	O
+all	O
+9	O
+cases	O
+stained	O
+,	O
+positive	O
+for	O
+HMB	B-GENE
+-	I-GENE
+45	I-GENE
+in	O
+9	O
+(	O
+90	O
+%	O
+)	O
+of	O
+10	O
+,	O
+and	O
+negative	O
+for	O
+cytokeratin	B-GENE
+in	O
+all	O
+9	O
+cases	O
+in	O
+which	O
+myxoid	O
+melanoma	O
+remained	O
+in	O
+the	O
+block	O
+after	O
+previous	O
+sections	O
+.	O
+
+Patients	O
+with	O
+types	O
+I	O
+and	O
+III	O
+MPGN	O
+did	O
+not	O
+differ	O
+in	O
+age	O
+at	O
+apparent	O
+onset	O
+,	O
+age	O
+at	O
+diagnosis	O
+,	O
+or	O
+interval	O
+from	O
+apparent	O
+onset	O
+of	O
+symptoms	O
+to	O
+diagnosis	O
+(	O
+biopsy	O
+)	O
+.	O
+
+Residual	O
+urinary	O
+abnormalities	O
+were	O
+significantly	O
+more	O
+frequent	O
+in	O
+patients	O
+with	O
+type	O
+III	O
+than	O
+type	O
+I	O
+MPGN	O
+.	O
+
+Taken	O
+together	O
+,	O
+differences	O
+in	O
+signaling	O
+and	O
+tissue	O
+expression	O
+suggest	O
+that	O
+the	O
+human	B-GENE
+intermediate	I-GENE
+PRLr	I-GENE
+differs	O
+from	O
+the	O
+long	B-GENE
+PRLr	I-GENE
+in	O
+physiological	O
+function	O
+.	O
+
+We	O
+describe	O
+here	O
+a	O
+Drosophila	B-GENE
+melanogaster	I-GENE
+FAK	I-GENE
+homologue	I-GENE
+,	O
+DFak56	B-GENE
+,	O
+which	O
+maps	O
+to	O
+band	O
+56D	O
+on	O
+the	O
+right	O
+arm	O
+of	O
+the	O
+second	O
+chromosome	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+the	O
+third	O
+SH3	B-GENE
+domain	I-GENE
+binds	O
+to	O
+Sos	B-GENE
+,	O
+a	O
+guanine	B-GENE
+nucleotide	I-GENE
+exchange	I-GENE
+factor	I-GENE
+for	O
+Ras	B-GENE
+and	O
+Rac	B-GENE
+,	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+Point	O
+mutations	O
+in	O
+the	O
+third	O
+SH3	B-GENE
+domain	I-GENE
+abolished	O
+the	O
+vinexin	B-GENE
+-	O
+Sos	B-GENE
+interaction	O
+.	O
+
+In	O
+gel	O
+mobility	O
+shift	O
+assays	O
+,	O
+low	O
+binding	O
+activity	O
+of	O
+CBF	B-GENE
+to	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+AtpC	I-GENE
+promoter	I-GENE
+sequence	I-GENE
+was	O
+observed	O
+with	O
+nuclear	O
+extracts	O
+from	O
+tissue	O
+with	O
+low	O
+AtpC	B-GENE
+expression	O
+levels	O
+,	O
+i	O
+.	O
+e	O
+.	O
+extracts	O
+from	O
+etiolated	O
+and	O
+photobleached	O
+seedlings	O
+,	O
+whereas	O
+high	O
+binding	O
+activity	O
+was	O
+detectable	O
+with	O
+extracts	O
+from	O
+tissues	O
+with	O
+high	O
+AtpC	B-GENE
+expression	O
+levels	O
+,	O
+i	O
+.	O
+e	O
+.	O
+extracts	O
+from	O
+light	O
+-	O
+grown	O
+seedlings	O
+and	O
+etiolated	O
+seedlings	O
+treated	O
+with	O
+cytokinin	B-GENE
+.	O
+
+They	O
+are	O
+subdivided	O
+into	O
+two	O
+types	O
+that	O
+activate	O
+transduction	O
+pathways	O
+via	O
+different	O
+cell	O
+surface	O
+receptors	O
+.	O
+
+We	O
+report	O
+here	O
+that	O
+out	O
+of	O
+the	O
+major	O
+pro	O
+-	O
+inflammatory	O
+cytokines	O
+examined	O
+,	O
+IL	B-GENE
+-	I-GENE
+1alpha	I-GENE
+,	O
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+,	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+,	O
+only	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+was	O
+generated	O
+and	O
+secreted	O
+in	O
+PKCeta	B-GENE
+-	O
+expressing	O
+cells	O
+without	O
+any	O
+additional	O
+inducer	O
+in	O
+serum	O
+-	O
+supplemented	O
+cultures	O
+(	O
+10	O
+%	O
+FCS	O
+)	O
+.	O
+
+Demyelinating	O
+diseases	O
+involving	O
+the	O
+grey	O
+matter	O
+were	O
+very	O
+rare	O
+,	O
+but	O
+we	O
+must	O
+consider	O
+the	O
+presence	O
+of	O
+symmetrical	O
+thalamic	O
+involvement	O
+in	O
+patients	O
+with	O
+ADEM	O
+.	O
+
+To	O
+define	O
+the	O
+minimal	O
+VDRE	O
+binding	O
+domain	O
+for	O
+human	B-GENE
+VDR	I-GENE
+(	O
+hVDR	B-GENE
+)	O
+,	O
+a	O
+series	O
+of	O
+C	O
+-	O
+terminally	O
+truncated	O
+hVDR	B-GENE
+mutants	I-GENE
+(	O
+Delta134	O
+,	O
+Delta113	O
+,	O
+Delta102	O
+,	O
+Delta90	O
+,	O
+Delta84	O
+,	O
+Delta80	O
+,	O
+and	O
+Delta60	O
+)	O
+was	O
+generated	O
+and	O
+expressed	O
+in	O
+bacteria	O
+.	O
+
+These	O
+REPs	O
+,	O
+or	O
+clusters	O
+of	O
+paralogous	O
+loci	O
+,	O
+are	O
+15	O
+-	O
+100	O
+kb	O
+and	O
+harbor	O
+at	O
+least	O
+four	O
+ESTs	O
+and	O
+an	O
+expressed	O
+SH3GL	B-GENE
+pseudogene	I-GENE
+.	O
+
+In	O
+part	O
+as	O
+a	O
+result	O
+of	O
+its	O
+inability	O
+to	O
+sustain	O
+radiative	O
+loses	O
+,	O
+the	O
+BB	O
+resonator	O
+has	O
+extremely	O
+low	O
+RF	O
+power	O
+requirements	O
+.	O
+
+In	O
+addition	O
+,	O
+narZ	B-GENE
+expression	O
+was	O
+induced	O
+approximately	O
+20	O
+-	O
+fold	O
+intracellularly	O
+in	O
+Madin	O
+-	O
+Darby	O
+canine	O
+kidney	O
+epithelial	O
+cells	O
+and	O
+16	O
+-	O
+fold	O
+in	O
+intracellular	O
+salts	O
+medium	O
+,	O
+which	O
+is	O
+believed	O
+to	O
+mimic	O
+the	O
+intracellular	O
+milieu	O
+.	O
+
+However	O
+,	O
+mechanisms	O
+underlying	O
+HIV	O
+-	O
+1	O
+gene	O
+expression	O
+in	O
+the	O
+CNS	O
+are	O
+poorly	O
+understood	O
+.	O
+
+Is	O
+radical	O
+trachelectomy	O
+a	O
+safe	O
+alternative	O
+to	O
+radical	O
+hysterectomy	O
+for	O
+patients	O
+with	O
+stage	O
+IA	O
+-	O
+B	O
+carcinoma	O
+of	O
+the	O
+cervix	O
+?	O
+BACKGROUND	O
+:	O
+The	O
+prognosis	O
+associated	O
+with	O
+lymph	O
+node	O
+negative	O
+,	O
+early	O
+stage	O
+carcinoma	O
+of	O
+the	O
+cervix	O
+is	O
+excellent	O
+,	O
+with	O
+5	O
+-	O
+year	O
+survival	O
+rates	O
+greater	O
+than	O
+90	O
+%	O
+.	O
+
+A	O
+key	O
+event	O
+in	O
+this	O
+process	O
+is	O
+the	O
+selective	O
+recognition	O
+of	O
+the	O
+target	O
+membrane	O
+by	O
+the	O
+vesicle	O
+and	O
+the	O
+current	O
+view	O
+is	O
+that	O
+SNARE	B-GENE
+protein	I-GENE
+interactions	O
+likely	O
+play	O
+a	O
+central	O
+role	O
+in	O
+vesicle	O
+-	O
+target	O
+recognition	O
+and	O
+or	O
+membrane	O
+fusion	O
+.	O
+
+Scapulae	O
+with	O
+a	O
+Type	O
+I	O
+configuration	O
+were	O
+found	O
+to	O
+have	O
+low	O
+values	O
+for	O
+the	O
+coraco	O
+-	O
+glenoid	O
+angle	O
+and	O
+coracoid	O
+overlap	O
+,	O
+which	O
+are	O
+known	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+short	O
+coraco	O
+-	O
+humeral	O
+distance	O
+.	O
+
+Measurements	O
+in	O
+the	O
+LWS	O
+p	O
+.	O
+a	O
+.	O
+,	O
+LWS	O
+lat	O
+.	O
+and	O
+at	O
+Ward	O
+'	O
+s	O
+triangle	O
+were	O
+made	O
+in	O
+a	O
+total	O
+of	O
+100	O
+patients	O
+.	O
+
+A	O
+group	O
+of	O
+66	O
+DSM	O
+-	O
+IV	O
+paranoid	O
+schizophrenic	O
+in	O
+-	O
+patients	O
+were	O
+assessed	O
+three	O
+times	O
+using	O
+the	O
+SAPS	O
+,	O
+SANS	O
+,	O
+BPRS	O
+and	O
+PAS	O
+.	O
+
+Despite	O
+the	O
+high	O
+frequency	O
+of	O
+natural	O
+infection	O
+,	O
+the	O
+seropositive	O
+rates	O
+of	O
+JEV	O
+antibody	O
+still	O
+correlated	O
+well	O
+with	O
+the	O
+dose	O
+of	O
+vaccine	O
+received	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+67	O
+%	O
+(	O
+1122	O
+/	O
+1664	O
+)	O
+,	O
+66	O
+%	O
+(	O
+65	O
+/	O
+97	O
+)	O
+,	O
+33	O
+%	O
+(	O
+4	O
+/	O
+12	O
+)	O
+and	O
+40	O
+%	O
+(	O
+19	O
+/	O
+47	O
+)	O
+for	O
+children	O
+receiving	O
+3	O
+,	O
+2	O
+,	O
+1	O
+,	O
+and	O
+0	O
+dose	O
+of	O
+JE	O
+vaccines	O
+,	O
+respectively	O
+(	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+Chi	O
+-	O
+square	O
+for	O
+trend	O
+test	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+in	O
+vivo	O
+and	O
+in	O
+vitro	O
+protein	O
+-	O
+protein	O
+interaction	O
+experiments	O
+have	O
+shown	O
+that	O
+SR33	B-GENE
+protein	I-GENE
+interacts	O
+with	O
+itself	O
+and	O
+with	O
+SR45	B-GENE
+protein	I-GENE
+but	O
+not	O
+with	O
+two	O
+other	O
+members	O
+(	O
+SRZ21	B-GENE
+and	O
+SRZ22	B-GENE
+)	O
+of	O
+the	O
+SR	B-GENE
+family	I-GENE
+that	O
+are	O
+known	O
+to	O
+interact	O
+with	O
+the	O
+Arabidopsis	O
+full	O
+-	O
+length	O
+U	B-GENE
+-	I-GENE
+70K	I-GENE
+only	O
+.	O
+
+In	O
+summary	O
+,	O
+WT1	B-GENE
+is	O
+enriched	O
+by	O
+oligo	O
+(	O
+dT	O
+)	O
+chromatography	O
+,	O
+as	O
+are	O
+U2AF65	B-GENE
+,	O
+the	O
+U5	B-GENE
+small	I-GENE
+nuclear	I-GENE
+RNP	I-GENE
+-	I-GENE
+associated	I-GENE
+protein	I-GENE
+p116	B-GENE
+and	O
+hnRNP	O
+A1	B-GENE
+.	O
+
+Six	O
+out	O
+of	O
+ten	O
+hearts	O
+from	O
+macerated	O
+stillborn	O
+infants	O
+showed	O
+varying	O
+degrees	O
+of	O
+positive	O
+staining	O
+.	O
+
+Tih1	B-GENE
+maps	O
+to	O
+distal	O
+mouse	O
+Chr	O
+1	O
+and	O
+human	O
+Chr	O
+1q31	O
+,	O
+chromosomal	O
+regions	O
+that	O
+have	O
+not	O
+shown	O
+evidence	O
+for	O
+imprinting	O
+and	O
+,	O
+in	O
+contrast	O
+to	O
+Ipl	B-GENE
+,	O
+Tih1	B-GENE
+is	O
+expressed	O
+equally	O
+from	O
+both	O
+parental	O
+alleles	O
+.	O
+
+A	O
+novel	O
+pleckstrin	B-GENE
+homology	I-GENE
+-	I-GENE
+related	I-GENE
+gene	I-GENE
+family	I-GENE
+defined	O
+by	O
+Ipl	B-GENE
+/	O
+Tssc3	B-GENE
+,	O
+TDAG51	B-GENE
+,	O
+and	O
+Tih1	B-GENE
+:	O
+tissue	O
+-	O
+specific	O
+expression	O
+,	O
+chromosomal	O
+location	O
+,	O
+and	O
+parental	O
+imprinting	O
+.	O
+
+The	O
+potential	O
+for	O
+highly	O
+reactive	O
+nanoparticles	O
+(	O
+RNP	O
+)	O
+to	O
+absorb	O
+destructively	O
+,	O
+i	O
+.	O
+e	O
+.	O
+to	O
+neutralize	O
+highly	O
+toxic	O
+substances	O
+such	O
+as	O
+the	O
+warfare	O
+agents	O
+GA	O
+,	O
+GB	O
+,	O
+HD	O
+and	O
+VX	O
+,	O
+has	O
+been	O
+demonstrated	O
+in	O
+the	O
+laboratory	O
+.	O
+
+There	O
+were	O
+minimal	O
+negative	O
+effects	O
+on	O
+hematological	O
+parameters	O
+,	O
+acid	O
+-	O
+base	O
+status	O
+,	O
+and	O
+blood	O
+gases	O
+.	O
+
+Twelve	O
+out	O
+of	O
+43	O
+renal	O
+failure	O
+patients	O
+had	O
+troponin	B-GENE
+I	I-GENE
+0	O
+.	O
+13	O
+-	O
+0	O
+.	O
+9	O
+microg	O
+/	O
+l	O
+using	O
+Axsym	O
+method	O
+and	O
+4	O
+had	O
+levels	O
+of	O
+0	O
+.	O
+07	O
+-	O
+0	O
+.	O
+13	O
+microg	O
+/	O
+l	O
+using	O
+Immuno	O
+1	O
+.	O
+
+Therefore	O
+,	O
+we	O
+propose	O
+that	O
+p27	B-GENE
+represents	O
+a	O
+crucial	O
+molecule	O
+in	O
+HMBA	O
+signaling	O
+that	O
+cannot	O
+be	O
+replaced	O
+by	O
+p21	B-GENE
+.	O
+
+Transient	O
+,	O
+high	O
+-	O
+level	O
+Ras	B-GENE
+-	O
+expression	O
+induces	O
+transcriptional	O
+activation	O
+of	O
+p21	B-GENE
+mediated	O
+by	O
+a	O
+GC	O
+-	O
+rich	O
+region	O
+in	O
+p21	B-GENE
+promoter	I-GENE
+-	O
+83	O
+-	O
+54	O
+bp	O
+relative	O
+to	O
+the	O
+transcription	O
+initiation	O
+site	O
+containing	O
+binding	O
+sites	O
+for	O
+Sp1	B-GENE
+-	I-GENE
+family	I-GENE
+transcription	I-GENE
+factors	I-GENE
+.	O
+
+The	O
+RET	B-GENE
+/	O
+PTC3	B-GENE
+rearrangement	O
+is	O
+formed	O
+by	O
+fusion	O
+of	O
+the	O
+ELE1	B-GENE
+and	O
+RET	B-GENE
+genes	I-GENE
+,	O
+and	O
+is	O
+highly	O
+prevalent	O
+in	O
+radiation	O
+-	O
+induced	O
+post	O
+-	O
+Chernobyl	O
+papillary	O
+thyroid	O
+carcinomas	O
+.	O
+
+Apoptosis	O
+of	O
+small	O
+cells	O
+is	O
+still	O
+observed	O
+after	O
+co	O
+-	O
+transfection	O
+of	O
+JBD	B-GENE
+and	O
+LMP1	B-GENE
+but	O
+in	O
+addition	O
+a	O
+few	O
+apoptotic	O
+HD	O
+-	O
+MyZ	O
+cells	O
+with	O
+large	O
+fused	O
+nuclear	O
+masses	O
+are	O
+identified	O
+suggesting	O
+that	O
+specific	O
+inhibition	O
+of	O
+JNK	B-GENE
+leads	O
+also	O
+to	O
+apoptosis	O
+of	O
+LMP1	B-GENE
+induced	O
+RS	O
+cells	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+bZIP	B-GENE
+protein	I-GENE
+Opaque2	I-GENE
+(	O
+O2	B-GENE
+)	O
+,	O
+there	O
+are	O
+other	O
+maize	O
+endosperm	O
+nuclear	O
+proteins	O
+that	O
+recognize	O
+the	O
+O2	B-GENE
+box	I-GENE
+in	O
+22	O
+kDa	O
+zein	B-GENE
+gene	O
+promoters	O
+.	O
+
+The	O
+mEmBP	B-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+can	O
+activate	O
+transcription	O
+from	O
+a	O
+truncated	O
+promoter	O
+containing	O
+a	O
+pentamer	O
+of	O
+the	O
+O2	B-GENE
+site	I-GENE
+in	O
+yeast	O
+cells	O
+;	O
+however	O
+,	O
+it	O
+inhibited	O
+regulated	O
+transcription	O
+of	O
+a	O
+22	B-GENE
+kDa	I-GENE
+zein	I-GENE
+promoter	I-GENE
+in	O
+a	O
+transient	O
+expression	O
+assay	O
+using	O
+cultured	O
+maize	O
+endosperm	O
+cells	O
+.	O
+
+GHB	O
+,	O
+2	O
+CB	O
+,	O
+HMB	O
+,	O
+are	O
+some	O
+of	O
+these	O
+recent	O
+substances	O
+.	O
+
+There	O
+were	O
+15	O
+deaths	O
+,	O
+seven	O
+of	O
+which	O
+were	O
+felt	O
+to	O
+be	O
+avoidable	O
+.	O
+
+With	O
+this	O
+GH	B-GENE
+and	O
+estrogen	O
+treatment	O
+regimen	O
+,	O
+most	O
+girls	O
+with	O
+TS	O
+can	O
+grow	O
+and	O
+develop	O
+much	O
+more	O
+in	O
+conformity	O
+with	O
+their	O
+healthy	O
+peers	O
+.	O
+
+We	O
+propose	O
+that	O
+the	O
+reduced	O
+responsiveness	O
+of	O
+CYP3A2	B-GENE
+is	O
+the	O
+result	O
+of	O
+preferential	O
+binding	O
+of	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+at	O
+the	O
+CYP3A2	B-GENE
+DexRE	I-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+.	O
+
+Higher	O
+CYP3A23	B-GENE
+basal	O
+activity	O
+appears	O
+to	O
+be	O
+due	O
+to	O
+an	O
+E	O
+-	O
+box	O
+in	O
+3A23SiteA	B-GENE
+that	O
+interacts	O
+with	O
+USF1	B-GENE
+,	O
+a	O
+ubiquitous	O
+bHLH	B-GENE
+/	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+transcription	I-GENE
+factor	I-GENE
+.	O
+
+The	O
+first	O
+one	O
+is	O
+a	O
+TPA	O
+-	O
+responsive	O
+element	O
+that	O
+controls	O
+the	O
+base	O
+-	O
+line	O
+ST3	B-GENE
+promoter	I-GENE
+activity	O
+but	O
+is	O
+not	O
+required	O
+for	O
+its	O
+activation	O
+.	O
+
+To	O
+understand	O
+the	O
+basis	O
+for	O
+the	O
+increased	O
+cell	O
+surface	O
+stability	O
+compared	O
+with	O
+wild	O
+-	O
+type	O
+peptide	O
+and	O
+to	O
+understand	O
+the	O
+differences	O
+in	O
+T	O
+cell	O
+recognition	O
+between	O
+I1Y	B-GENE
+and	O
+I1F	B-GENE
+,	O
+we	O
+determined	O
+the	O
+x	O
+-	O
+ray	O
+crystal	O
+structures	O
+of	O
+the	O
+two	O
+class	B-GENE
+I	I-GENE
+MHC	I-GENE
+-	I-GENE
+peptide	I-GENE
+complexes	I-GENE
+.	O
+
+Redistribution	O
+of	O
+mannosidase	B-GENE
+I	I-GENE
+was	O
+also	O
+observed	O
+in	O
+cells	O
+incubated	O
+at	O
+15	O
+degrees	O
+C	O
+.	O
+
+In	O
+addition	O
+,	O
+using	O
+biochemical	O
+activity	O
+assays	O
+for	O
+Rho	B-GENE
+-	O
+like	O
+GTPases	B-GENE
+,	O
+we	O
+show	O
+that	O
+the	O
+expression	O
+of	O
+beta1A	B-GENE
+,	O
+beta1D	B-GENE
+,	O
+or	O
+IL2R	B-GENE
+-	O
+beta1A	B-GENE
+in	O
+GE11	O
+or	O
+GD25	O
+cells	O
+triggers	O
+activation	O
+of	O
+both	O
+RhoA	B-GENE
+and	O
+Rac1	B-GENE
+,	O
+but	O
+not	O
+of	O
+Cdc42	B-GENE
+.	O
+
+In	O
+conclusion	O
+,	O
+our	O
+data	O
+do	O
+not	O
+support	O
+a	O
+role	O
+for	O
+IVIg	B-GENE
+in	O
+the	O
+remyelination	O
+of	O
+stable	O
+multiple	O
+sclerosis	O
+lesions	O
+as	O
+measured	O
+by	O
+central	O
+conduction	O
+time	O
+.	O
+
+The	O
+rhabdomyosarcoma	O
+R1H	O
+growing	O
+on	O
+the	O
+right	O
+flank	O
+of	O
+male	O
+WAG	O
+/	O
+Rij	O
+rats	O
+was	O
+clamped	O
+for	O
+2	O
+or	O
+4	O
+h	O
+at	O
+20	O
+degrees	O
+C	O
+or	O
+37	O
+degrees	O
+C	O
+.	O
+
+Relative	O
+to	O
+coherent	O
+control	O
+words	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+quick	O
+)	O
+,	O
+these	O
+discourse	O
+-	O
+dependent	O
+semantic	O
+anomalies	O
+elicited	O
+a	O
+large	O
+N400	O
+effect	O
+that	O
+began	O
+at	O
+about	O
+200	O
+to	O
+250	O
+msec	O
+after	O
+word	O
+onset	O
+.	O
+
+These	O
+synergistic	O
+effects	O
+were	O
+strongly	O
+Jem	B-GENE
+-	I-GENE
+1	I-GENE
+dose	O
+-	O
+dependent	O
+.	O
+
+Like	O
+the	O
+Tob	B-GENE
+protein	I-GENE
+,	O
+Tob2	B-GENE
+inhibited	O
+cell	O
+cycle	O
+progression	O
+from	O
+the	O
+G0	O
+/	O
+G1	O
+to	O
+S	O
+phases	O
+.	O
+
+The	O
+coordinate	O
+increase	O
+in	O
+cyclin	B-GENE
+D1	I-GENE
+and	O
+p21	B-GENE
+had	O
+the	O
+effect	O
+of	O
+decreasing	O
+the	O
+specific	O
+but	O
+not	O
+absolute	O
+activity	O
+of	O
+cyclin	B-GENE
+D1	I-GENE
+/	O
+cdk4	B-GENE
+.	O
+p53	B-GENE
+was	O
+not	O
+involved	O
+since	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+induction	O
+of	O
+p21	B-GENE
+was	O
+unaffected	O
+by	O
+dominant	B-GENE
+-	I-GENE
+negative	I-GENE
+p53	I-GENE
+expression	O
+.	O
+
+In	O
+addition	O
+,	O
+SLK	B-GENE
+displays	O
+high	O
+homology	O
+to	O
+microtubule	B-GENE
+and	I-GENE
+nuclear	I-GENE
+associated	I-GENE
+protein	I-GENE
+(	O
+M	B-GENE
+-	I-GENE
+NAP	I-GENE
+)	O
+and	O
+AT1	B-GENE
+-	I-GENE
+46	I-GENE
+,	O
+both	O
+of	O
+unknown	O
+function	O
+.	O
+
+In	O
+this	O
+study	O
+26	O
+patients	O
+(	O
+20	O
+females	O
+and	O
+6	O
+males	O
+)	O
+were	O
+evaluated	O
+.	O
+
+The	O
+signalling	O
+molecules	O
+Wnt1	B-GENE
+and	O
+Sonic	B-GENE
+hedgehog	I-GENE
+,	O
+implicated	O
+in	O
+the	O
+activation	O
+of	O
+Myf5	B-GENE
+in	O
+myogenic	O
+progenitor	O
+cells	O
+in	O
+the	O
+somite	O
+,	O
+are	O
+also	O
+produced	O
+in	O
+the	O
+viscinity	O
+of	O
+the	O
+Myf5	B-GENE
+expression	I-GENE
+domain	I-GENE
+in	O
+the	O
+mesencephalon	O
+.	O
+
+STUDY	O
+DESIGN	O
+AND	O
+METHODS	O
+:	O
+A	O
+study	O
+was	O
+initiated	O
+to	O
+compare	O
+the	O
+collection	O
+of	O
+PBPCs	O
+with	O
+the	O
+new	O
+device	O
+,	O
+the	O
+AutoPBSC	O
+(	O
+version	O
+[	O
+V	O
+]	O
+6	O
+.	O
+0	O
+with	O
+AutoPBSC	O
+tubing	O
+set	O
+)	O
+,	O
+and	O
+that	O
+with	O
+the	O
+MNC	O
+(	O
+mononuclear	O
+cell	O
+)	O
+procedure	O
+(	O
+V4	O
+.	O
+7	O
+with	O
+white	O
+cell	O
+tubing	O
+set	O
+)	O
+,	O
+for	O
+patients	O
+and	O
+healthy	O
+donors	O
+.	O
+
+Albumin	B-GENE
+dialysis	O
+:	O
+effective	O
+removal	O
+of	O
+copper	O
+in	O
+a	O
+patient	O
+with	O
+fulminant	O
+Wilson	O
+disease	O
+and	O
+successful	O
+bridging	O
+to	O
+liver	O
+transplantation	O
+:	O
+a	O
+new	O
+possibility	O
+for	O
+the	O
+elimination	O
+of	O
+protein	O
+-	O
+bound	O
+toxins	O
+.	O
+
+Some	O
+artificial	O
+promoter	O
+constructs	O
+containing	O
+multiple	O
+Sp1	B-GENE
+sites	I-GENE
+were	O
+highly	O
+responsive	O
+to	O
+ethanol	O
+,	O
+but	O
+others	O
+were	O
+not	O
+,	O
+suggesting	O
+that	O
+the	O
+organization	O
+of	O
+the	O
+proximal	O
+promoter	O
+region	O
+was	O
+an	O
+additional	O
+factor	O
+that	O
+affected	O
+the	O
+ethanol	O
+response	O
+.	O
+
+Overexpression	O
+of	O
+CDP	B-GENE
+/	O
+cut	B-GENE
+in	O
+ROS	O
+17	O
+/	O
+2	O
+.	O
+8	O
+osteosarcoma	O
+cells	O
+results	O
+in	O
+repression	O
+of	O
+OC	B-GENE
+promoter	I-GENE
+activity	O
+;	O
+this	O
+repression	O
+is	O
+abrogated	O
+by	O
+mutating	O
+OC	B-GENE
+box	I-GENE
+I	I-GENE
+.	O
+
+Injection	O
+of	O
+double	O
+-	O
+stranded	O
+RNA	O
+into	O
+C	O
+.	O
+elegans	O
+results	O
+in	O
+embryonic	O
+lethality	O
+;	O
+thus	O
+,	O
+the	O
+SF1	B-GENE
+gene	I-GENE
+is	O
+essential	O
+not	O
+only	O
+in	O
+yeast	O
+but	O
+also	O
+in	O
+at	O
+least	O
+one	O
+metazoan	O
+.	O
+
+Both	O
+domains	O
+were	O
+required	O
+for	O
+specific	O
+DNA	O
+binding	O
+to	O
+the	O
+beta	B-GENE
+-	I-GENE
+retinoic	I-GENE
+acid	I-GENE
+receptor	I-GENE
+element	I-GENE
+,	O
+producing	O
+a	O
+DNase	B-GENE
+I	I-GENE
+footprint	O
+covering	O
+predominantly	O
+one	O
+strand	O
+.	O
+
+Snail	B-GENE
+family	I-GENE
+proteins	I-GENE
+are	O
+zinc	O
+finger	O
+transcriptional	O
+regulators	O
+first	O
+identified	O
+in	O
+Drosophila	O
+which	O
+play	O
+critical	O
+roles	O
+in	O
+cell	O
+fate	O
+determination	O
+.	O
+
+Consistent	O
+with	O
+this	O
+finding	O
+,	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+interacted	O
+directly	O
+with	O
+the	O
+RA	B-GENE
+receptor	I-GENE
+(	O
+RAR	B-GENE
+)	O
+in	O
+a	O
+retinoid	O
+-	O
+dependent	O
+manner	O
+,	O
+but	O
+not	O
+with	O
+the	O
+retinoid	B-GENE
+X	I-GENE
+receptor	I-GENE
+(	O
+RXR	B-GENE
+)	O
+,	O
+and	O
+RAR	B-GENE
+competed	O
+with	O
+TCF	B-GENE
+for	O
+beta	B-GENE
+-	I-GENE
+catenin	I-GENE
+binding	O
+.	O
+
+Thrombolysis	O
+was	O
+followed	O
+by	O
+a	O
+similar	O
+increase	O
+of	O
+platelet	O
+activity	O
+with	O
+maximal	O
+values	O
+reached	O
+at	O
+the	O
+3rd	O
+hour	O
+in	O
+both	O
+groups	O
+(	O
+196	O
++	O
+/	O
+-	O
+43	O
+IU	O
+/	O
+ml	O
+in	O
+Group	O
+1	O
+and	O
+192	O
++	O
+/	O
+-	O
+39	O
+in	O
+Group	O
+2	O
+:	O
+p	O
+&	O
+lt	O
+;	O
+001versus	O
+baseline	O
+and	O
+p	O
+NS	O
+between	O
+the	O
+groups	O
+)	O
+.	O
+
+Similar	O
+to	O
+Hp140	B-GENE
+,	O
+isolated	O
+Hp55	B-GENE
+binds	O
+DNA	O
+with	O
+moderate	O
+strength	O
+and	O
+was	O
+a	O
+specificity	O
+for	O
+double	O
+-	O
+stranded	O
+primer	O
+-	O
+template	O
+DNA	O
+.	O
+
+Finally	O
+,	O
+three	O
+new	O
+missense	O
+mutations	O
+,	O
+E138V	O
+,	O
+R254G	O
+,	O
+and	O
+P362R	O
+,	O
+were	O
+identified	O
+in	O
+the	O
+human	B-GENE
+AC	I-GENE
+gene	I-GENE
+from	O
+FD	O
+patients	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+interaction	O
+of	O
+eIF4A	B-GENE
+with	O
+the	O
+middle	O
+region	O
+of	O
+eIF4GI	B-GENE
+is	O
+necessary	O
+for	O
+translation	O
+,	O
+whereas	O
+the	O
+interaction	O
+of	O
+eIF4A	B-GENE
+with	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+plays	O
+a	O
+modulatory	O
+role	O
+.	O
+
+The	O
+DAP5	B-GENE
+/	O
+p86	B-GENE
+apoptotic	O
+form	O
+was	O
+more	O
+potent	O
+than	O
+DAP5	B-GENE
+/	O
+p97	B-GENE
+in	O
+these	O
+functional	O
+assays	O
+.	O
+
+12	O
+:	O
+2684	O
+-	O
+2697	O
+,	O
+1998	O
+)	O
+:	O
+a	O
+key	O
+step	O
+of	O
+this	O
+model	O
+is	O
+the	O
+activation	O
+of	O
+the	O
+MAPK	B-GENE
+Fus3p	I-GENE
+through	O
+the	O
+G	B-GENE
+(	I-GENE
+betagamma	I-GENE
+)	I-GENE
+-	O
+dependent	O
+relocalization	O
+of	O
+the	O
+Ste5p	B-GENE
+-	O
+MAPK	B-GENE
+cascade	O
+to	O
+the	O
+plasma	O
+membrane	O
+.	O
+
+Consistent	O
+with	O
+this	O
+finding	O
+,	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+SAGA	I-GENE
+inhibits	O
+TBP	B-GENE
+binding	O
+to	O
+the	O
+HIS3	B-GENE
+promoter	I-GENE
+in	O
+vitro	O
+,	O
+while	O
+SAGA	B-GENE
+lacking	O
+Spt3	B-GENE
+or	O
+Spt8	B-GENE
+is	O
+not	O
+inhibitory	O
+.	O
+
+Saccharomyces	O
+cerevisiae	O
+contains	O
+a	O
+genetically	O
+and	O
+biochemically	O
+proven	O
+CAK	B-GENE
+gene	I-GENE
+,	O
+CAK1	B-GENE
+,	O
+that	O
+encodes	O
+a	O
+monomeric	O
+44	B-GENE
+-	I-GENE
+kDa	I-GENE
+Cak1p	I-GENE
+protein	I-GENE
+unrelated	O
+to	O
+Cdk7	B-GENE
+.	O
+
+Northern	O
+blot	O
+and	O
+reverse	O
+transcription	O
+-	O
+PCR	O
+analyses	O
+of	O
+human	O
+mRNA	O
+samples	O
+demonstrate	O
+that	O
+RNR	B-GENE
+is	O
+expressed	O
+exclusively	O
+in	O
+the	O
+retina	O
+,	O
+with	O
+transcripts	O
+of	O
+approximately	O
+7	O
+.	O
+5	O
+kb	O
+,	O
+approximately	O
+3	O
+.	O
+0	O
+kb	O
+,	O
+and	O
+approximately	O
+2	O
+.	O
+3	O
+kb	O
+by	O
+Northern	O
+blot	O
+analysis	O
+.	O
+
+Particularly	O
+striking	O
+was	O
+the	O
+conservation	O
+of	O
+an	O
+AP	B-GENE
+-	I-GENE
+4	I-GENE
+binding	I-GENE
+site	I-GENE
+within	O
+100	O
+nucleotides	O
+upstream	O
+of	O
+the	O
+transcription	O
+initiation	O
+site	O
+in	O
+both	O
+Aal	B-GENE
+-	O
+rpL34	B-GENE
+and	O
+Aal	B-GENE
+-	O
+rpL8	B-GENE
+genes	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Serum	O
+levels	O
+of	O
+S	B-GENE
+-	I-GENE
+100beta	I-GENE
+are	O
+reliable	O
+markers	O
+for	O
+adverse	O
+neurologic	O
+outcomes	O
+after	O
+cardiac	O
+surgery	O
+.	O
+
+All	O
+problems	O
+were	O
+associated	O
+with	O
+fractured	O
+or	O
+lost	O
+screws	O
+.	O
+
+The	O
+accumulated	O
+products	O
+of	O
+ancient	O
+duplication	O
+events	O
+can	O
+be	O
+readily	O
+observed	O
+among	O
+the	O
+genes	O
+encoding	O
+voltage	O
+-	O
+dependent	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+ion	O
+channels	O
+.	O
+
+The	O
+VirR	B-GENE
+response	I-GENE
+regulator	I-GENE
+from	O
+Clostridium	O
+perfringens	O
+binds	O
+independently	O
+to	O
+two	O
+imperfect	O
+direct	O
+repeats	O
+located	O
+upstream	O
+of	O
+the	O
+pfoA	B-GENE
+promoter	I-GENE
+.	O
+
+Cloning	O
+and	O
+sequencing	O
+of	O
+the	O
+upstream	O
+region	O
+of	O
+pepX	B-GENE
+revealed	O
+the	O
+presence	O
+of	O
+two	O
+ORFs	O
+of	O
+360	O
+and	O
+1	O
+,	O
+338	O
+bp	O
+that	O
+were	O
+shown	O
+to	O
+be	O
+able	O
+to	O
+encode	O
+proteins	O
+with	O
+high	O
+homology	O
+to	O
+GlnR	B-GENE
+and	O
+GlnA	B-GENE
+proteins	I-GENE
+,	O
+respectively	O
+.	O
+
+Objective	O
+:	O
+To	O
+evaluate	O
+endometrial	O
+thickness	O
+and	O
+the	O
+incidence	O
+of	O
+uterine	O
+bleeding	O
+in	O
+postmenopausal	O
+women	O
+using	O
+either	O
+tibolone	O
+2	O
+.	O
+5	O
+mg	O
+or	O
+continuous	O
+combined	O
+2	O
+mg	O
+estradiol	O
+and	O
+1	O
+mg	O
+norethisterone	O
+acetate	O
+(	O
+E	O
++	O
+NETA	O
+)	O
+daily	O
+as	O
+hormone	O
+replacement	O
+therapy	O
+.	O
+
+Histological	O
+analysis	O
+showed	O
+that	O
+the	O
+neuronal	O
+loss	O
+in	O
+the	O
+DHED	O
+-	O
+treated	O
+group	O
+was	O
+notably	O
+reduced	O
+in	O
+the	O
+hippocampal	O
+area	O
+(	O
+CA1	O
+)	O
+of	O
+ischemic	O
+rats	O
+and	O
+in	O
+the	O
+dentate	O
+gyrus	O
+and	O
+hippocampal	O
+area	O
+(	O
+CA1	O
+and	O
+CA3	O
+)	O
+of	O
+EC	O
+-	O
+lesioned	O
+rats	O
+compared	O
+with	O
+the	O
+nontreated	O
+group	O
+.	O
+
+The	O
+extents	O
+of	O
+phosphorylation	O
+of	O
+Ser44	O
+and	O
+Ser64	O
+were	O
+1	O
+:	O
+1	O
+,	O
+whereas	O
+those	O
+of	O
+the	O
+four	O
+minor	O
+sites	O
+all	O
+together	O
+were	O
+<	O
+30	O
+%	O
+of	O
+the	O
+major	O
+one	O
+.	O
+
+Serum	O
+HBV	O
+-	O
+DNA	O
+,	O
+viral	O
+serology	O
+,	O
+and	O
+liver	O
+enzymes	O
+were	O
+measured	O
+sequentially	O
+;	O
+liver	O
+histology	O
+was	O
+taken	O
+before	O
+and	O
+during	O
+treatment	O
+in	O
+12	O
+patients	O
+.	O
+
+Chem	O
+.	O
+
+Maximum	O
+induction	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+was	O
+reached	O
+at	O
+a	O
+concentration	O
+of	O
+250	O
+nmol	O
+/	O
+L	O
+of	O
+CalC	O
+.	O
+
+Rams	O
+were	O
+weighed	O
+and	O
+testis	O
+size	O
+was	O
+estimated	O
+by	O
+orchimetry	O
+at	O
+each	O
+time	O
+period	O
+.	O
+
+Animal	O
+studies	O
+showed	O
+that	O
+beam	O
+equalization	O
+significantly	O
+improved	O
+fluoroscopic	O
+and	O
+angiographic	O
+image	O
+quality	O
+.	O
+
+Role	O
+of	O
+estrogen	B-GENE
+receptor	I-GENE
+ligand	O
+and	O
+estrogen	O
+response	O
+element	O
+sequence	O
+on	O
+interaction	O
+with	O
+chicken	B-GENE
+ovalbumin	I-GENE
+upstream	I-GENE
+promoter	I-GENE
+transcription	I-GENE
+factor	I-GENE
+(	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+Cdks	B-GENE
+functioning	O
+throughout	O
+the	O
+cell	O
+cycle	O
+,	O
+tyrosine	O
+phosphorylation	O
+is	O
+inhibitory	O
+to	O
+the	O
+activation	O
+of	O
+kinase	O
+,	O
+whereas	O
+the	O
+phosphorylation	O
+of	O
+threonine	O
+in	O
+the	O
+T	O
+-	O
+loop	O
+is	O
+essential	O
+for	O
+activation	O
+.	O
+
+We	O
+also	O
+report	O
+that	O
+AHR	B-GENE
+interacts	O
+with	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+in	O
+transfected	O
+CV	O
+-	O
+1	O
+cells	O
+.	O
+
+AB004534	B-GENE
+.	O
+
+The	O
+prevalence	O
+of	O
+hepatitis	O
+C	O
+virus	O
+(	O
+HCV	O
+)	O
+infection	O
+is	O
+relatively	O
+low	O
+in	O
+childhood	O
+,	O
+with	O
+anti	B-GENE
+-	I-GENE
+HCV	I-GENE
+prevalence	O
+rates	O
+of	O
+0	O
+.	O
+1	O
+-	O
+0	O
+.	O
+4	O
+%	O
+in	O
+the	O
+Western	O
+world	O
+.	O
+
+Clear	O
+and	O
+evidenced	O
+-	O
+based	O
+information	O
+should	O
+be	O
+provided	O
+to	O
+patients	O
+as	O
+to	O
+the	O
+means	O
+of	O
+prevention	O
+with	O
+special	O
+attention	O
+to	O
+individual	O
+risk	O
+groups	O
+such	O
+as	O
+IV	O
+drug	O
+abusers	O
+.	O
+
+During	O
+latency	O
+,	O
+more	O
+than	O
+1	O
+%	O
+of	O
+neurons	O
+in	O
+ganglia	O
+that	O
+innervate	O
+the	O
+footpad	O
+expressed	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+,	O
+with	O
+the	O
+number	O
+of	O
+positive	O
+cells	O
+remaining	O
+constant	O
+for	O
+at	O
+least	O
+5	O
+months	O
+.	O
+
+As	O
+an	O
+alternative	O
+approach	O
+to	O
+this	O
+question	O
+,	O
+we	O
+have	O
+studied	O
+the	O
+effects	O
+of	O
+ectopically	O
+expressed	O
+SHIP	B-GENE
+,	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+or	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+SH2	O
+-	O
+containing	O
+decoy	O
+proteins	O
+on	O
+Fc	B-GENE
+gamma	I-GENE
+RIIB1	I-GENE
+signaling	O
+.	O
+
+Compared	O
+to	O
+those	O
+with	O
+normal	O
+renal	O
+functions	O
+,	O
+these	O
+patients	O
+were	O
+older	O
+(	O
+P	O
+<	O
+or	O
+=	O
+0	O
+.	O
+01	O
+)	O
+,	O
+had	O
+significantly	O
+elevated	O
+blood	O
+pressures	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+or	O
+P	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+,	O
+and	O
+in	O
+the	O
+case	O
+of	O
+Type	O
+1	O
+DM	O
+,	O
+with	O
+a	O
+higher	O
+body	O
+mass	O
+index	O
+(	O
+P	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+and	O
+waist	O
+-	O
+hip	O
+ratio	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+In	O
+all	O
+tissues	O
+examined	O
+only	O
+transcripts	O
+positive	O
+for	O
+insert	O
+3	O
+,	O
+an	O
+18	O
+bp	O
+insertion	O
+in	O
+repeat	O
+21	O
+,	O
+were	O
+amplified	O
+,	O
+even	O
+under	O
+conditions	O
+in	O
+which	O
+a	O
+30	O
+%	O
+level	O
+of	O
+insert	O
+3	O
+negative	O
+transcript	O
+could	O
+be	O
+easily	O
+detected	O
+in	O
+artificially	O
+prepared	O
+control	O
+samples	O
+.	O
+
+These	O
+results	O
+show	O
+that	O
+the	O
+CAAT	O
+-	O
+region	O
+is	O
+involved	O
+in	O
+upregulating	O
+the	O
+MDR1	B-GENE
+promoter	I-GENE
+in	O
+HL60	O
+/	O
+VCR	O
+cells	O
+.	O
+
+Both	O
+receptors	O
+utilize	O
+protein	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+(	O
+PTKs	B-GENE
+)	O
+for	O
+the	O
+phosphorylation	O
+of	O
+various	O
+signaling	O
+molecules	O
+,	O
+a	O
+process	O
+that	O
+is	O
+critical	O
+for	O
+the	O
+function	O
+of	O
+both	O
+receptors	O
+.	O
+
+The	O
+synergistic	O
+effect	O
+due	O
+to	O
+the	O
+5	O
+'	O
+-	O
+3	O
+'	O
+cooperation	O
+was	O
+at	O
+least	O
+fourfold	O
+greater	O
+than	O
+the	O
+sum	O
+of	O
+the	O
+contributions	O
+of	O
+the	O
+individual	O
+UTRs	O
+.	O
+
+We	O
+demonstrate	O
+that	O
+both	O
+R	B-GENE
+and	O
+Z	B-GENE
+activate	O
+the	O
+cellular	O
+stress	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinases	I-GENE
+,	O
+p38	B-GENE
+and	O
+JNK	B-GENE
+,	O
+resulting	O
+in	O
+phosphorylation	O
+(	O
+and	O
+activation	O
+)	O
+of	O
+the	O
+cellular	B-GENE
+transcription	I-GENE
+factor	I-GENE
+ATF2	I-GENE
+.	O
+
+Anatomy	O
+of	O
+the	O
+uterine	O
+artery	O
+.	O
+
+However	O
+,	O
+activation	O
+of	O
+the	O
+cAMP	O
+pathway	O
+,	O
+which	O
+is	O
+known	O
+to	O
+regulate	O
+inhibin	B-GENE
+alpha	I-GENE
+expression	O
+,	O
+greatly	O
+enhanced	O
+the	O
+actions	O
+of	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+Deletion	O
+and	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+localized	O
+a	O
+novel	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+regulatory	I-GENE
+element	I-GENE
+(	O
+TCA	O
+GGGCCA	O
+;	O
+-	O
+137	O
+to	O
+-	O
+129	O
+)	O
+adjacent	O
+to	O
+a	O
+variant	O
+cAMP	O
+-	O
+response	O
+element	O
+(	O
+CRE	O
+;	O
+-	O
+120	O
+to	O
+-	O
+114	O
+)	O
+.	O
+
+Synthetic	O
+ligands	O
+have	O
+been	O
+identified	O
+that	O
+reset	O
+and	O
+amplify	O
+the	O
+cycle	O
+of	O
+pulsatile	O
+GH	B-GENE
+secretion	O
+by	O
+interacting	O
+with	O
+the	O
+orphan	B-GENE
+GH	I-GENE
+-	I-GENE
+secretagogue	I-GENE
+receptor	I-GENE
+(	O
+GHS	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+.	O
+
+The	O
+collection	O
+of	O
+mutants	O
+displaying	O
+TGN	O
+sorting	O
+defects	O
+includes	O
+members	O
+with	O
+mutations	O
+in	O
+previously	O
+identified	O
+vacuolar	B-GENE
+protein	I-GENE
+sorting	I-GENE
+genes	I-GENE
+(	O
+VPS	B-GENE
+)	O
+,	O
+including	O
+the	O
+dynamin	B-GENE
+family	O
+member	O
+VPS1	B-GENE
+.	O
+
+Also	O
+in	O
+the	O
+spectrum	O
+of	O
+mutants	O
+with	O
+TGN	O
+sorting	O
+defects	O
+are	O
+isolates	O
+with	O
+mutations	O
+in	O
+the	O
+following	O
+:	O
+RIC1	B-GENE
+,	O
+encoding	O
+a	O
+product	O
+originally	O
+proposed	O
+to	O
+participate	O
+in	O
+ribosome	O
+biogenesis	O
+;	O
+LUV1	B-GENE
+,	O
+encoding	O
+a	O
+product	O
+potentially	O
+involved	O
+in	O
+vacuole	O
+and	O
+microtubule	O
+organization	O
+;	O
+and	O
+INP53	B-GENE
+,	O
+encoding	O
+a	O
+synaptojanin	B-GENE
+-	I-GENE
+like	I-GENE
+inositol	I-GENE
+polyphosphate	I-GENE
+5	I-GENE
+-	I-GENE
+phosphatase	I-GENE
+.	O
+
+The	O
+single	O
+strandedness	O
+is	O
+manifested	O
+as	O
+a	O
+terminal	O
+extension	O
+of	O
+the	O
+G	O
+-	O
+rich	O
+strand	O
+(	O
+G	O
+tails	O
+)	O
+that	O
+can	O
+occur	O
+independently	O
+of	O
+telomerase	B-GENE
+,	O
+suggesting	O
+that	O
+cdc17	B-GENE
+/	O
+pol1	B-GENE
+mutants	O
+exhibit	O
+defects	O
+in	O
+telomeric	O
+lagging	O
+-	O
+strand	O
+synthesis	O
+.	O
+
+In	O
+addition	O
+,	O
+CaMig1	B-GENE
+formed	O
+specific	O
+complexes	O
+with	O
+the	O
+URS1	O
+region	O
+of	O
+the	O
+S	B-GENE
+.	I-GENE
+cerevisiae	I-GENE
+FBP1	I-GENE
+gene	I-GENE
+.	O
+
+Furthermore	O
+,	O
+the	O
+wide	O
+distribution	O
+of	O
+the	O
+GFP	B-GENE
+-	O
+POLO	B-GENE
+protein	O
+to	O
+all	O
+compartments	O
+of	O
+the	O
+mitotic	O
+apparatus	O
+provides	O
+a	O
+valuable	O
+tool	O
+for	O
+future	O
+studies	O
+on	O
+cell	O
+cycle	O
+during	O
+development	O
+.	O
+
+An	O
+ASIC	O
+-	O
+chip	O
+for	O
+stereoscopic	O
+depth	O
+analysis	O
+in	O
+video	O
+-	O
+real	O
+-	O
+time	O
+based	O
+on	O
+visual	O
+cortical	O
+cell	O
+behavior	O
+.	O
+
+However	O
+,	O
+calphostin	O
+C	O
+,	O
+a	O
+specific	O
+inhibitor	O
+of	O
+PKC	B-GENE
+,	O
+abolished	O
+the	O
+TPA	O
+-	O
+induced	O
+increase	O
+in	O
+CFI	B-GENE
+mRNA	I-GENE
+levels	O
+.	O
+
+Preimmune	B-GENE
+IgG	I-GENE
+,	O
+anti	B-GENE
+-	I-GENE
+GalT	I-GENE
+Fab	I-GENE
+fragments	I-GENE
+,	O
+irrelevant	O
+polymers	O
+and	O
+monomeric	O
+N	O
+-	O
+acetylglucosamine	O
+had	O
+no	O
+effect	O
+.	O
+
+Downstream	O
+of	O
+the	O
+G	O
+-	O
+A	O
+anastomosis	O
+,	O
+the	O
+RD	O
+,	O
+CC	O
+,	O
+E	O
+(	O
+p	O
+)	O
+and	O
+loop	O
+areas	O
+were	O
+significantly	O
+different	O
+from	O
+REF	O
+,	O
+but	O
+significantly	O
+different	O
+from	O
+A	O
+-	O
+A	O
+.	O
+
+Induced	O
+expression	O
+of	O
+c	B-GENE
+-	I-GENE
+myc	I-GENE
+is	O
+likely	O
+to	O
+contribute	O
+to	O
+the	O
+proliferation	O
+of	O
+Stat1	B-GENE
+-	O
+null	O
+cells	O
+in	O
+response	O
+to	O
+IFNs	B-GENE
+.	O
+
+Eastern	O
+Cooperative	O
+Oncology	O
+Group	O
+trial	O
+E3186	O
+was	O
+initiated	O
+to	O
+explore	O
+this	O
+question	O
+.	O
+
+We	O
+determined	O
+how	O
+DNA	O
+repair	O
+is	O
+affected	O
+by	O
+TFA1	B-GENE
+conditional	O
+mutations	O
+.	O
+
+These	O
+articles	O
+both	O
+report	O
+the	O
+results	O
+of	O
+multi	O
+-	O
+institutional	O
+,	O
+randomized	O
+,	O
+phase	O
+3	O
+trials	O
+for	O
+the	O
+treatment	O
+of	O
+patients	O
+with	O
+localized	O
+(	O
+T1	O
+-	O
+3	O
+N0	O
+-	O
+1	O
+M0	O
+)	O
+esophageal	O
+squamous	O
+cell	O
+carcinoma	O
+(	O
+SCC	O
+)	O
+or	O
+esophageal	O
+adenocarcinoma	O
+.	O
+
+Studies	O
+of	O
+MPO	B-GENE
+gene	I-GENE
+regulation	O
+can	O
+help	O
+to	O
+elucidate	O
+the	O
+mechanism	O
+of	O
+normal	O
+and	O
+abnormal	O
+myeloid	O
+differentiation	O
+.	O
+
+NDRF	B-GENE
+/	O
+NeuroD2	B-GENE
+was	O
+co	O
+-	O
+precipitated	O
+with	O
+PKN	B-GENE
+from	O
+the	O
+lysate	O
+of	O
+COS	O
+-	O
+7	O
+cells	O
+transfected	O
+with	O
+both	O
+expression	O
+constructs	O
+for	O
+NDRF	B-GENE
+/	O
+NeuroD2	B-GENE
+and	O
+PKN	B-GENE
+.	O
+
+Transient	O
+transfection	O
+assays	O
+using	O
+P19	O
+cells	O
+revealed	O
+that	O
+expression	O
+of	O
+NDRF	B-GENE
+/	O
+NeuroD2	B-GENE
+increased	O
+the	O
+transactivation	O
+of	O
+the	O
+rat	B-GENE
+insulin	I-GENE
+promoter	I-GENE
+element	I-GENE
+3	I-GENE
+(	O
+RIPE3	B-GENE
+)	O
+enhancer	O
+up	O
+to	O
+approximately	O
+12	O
+-	O
+fold	O
+and	O
+that	O
+co	O
+-	O
+expression	O
+of	O
+catalytically	O
+active	O
+form	O
+of	O
+PKN	B-GENE
+,	O
+but	O
+not	O
+kinase	O
+-	O
+deficient	O
+derivative	O
+,	O
+resulted	O
+in	O
+a	O
+further	O
+threefold	O
+increase	O
+of	O
+NDRF	B-GENE
+/	O
+NeuroD2	B-GENE
+-	O
+mediated	O
+transcription	O
+.	O
+
+Two	O
+Pax2	B-GENE
+/	I-GENE
+5	I-GENE
+/	I-GENE
+8	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+Engrailed2	B-GENE
+are	O
+required	O
+for	O
+proper	O
+initiation	O
+of	O
+endogenous	O
+mid	O
+-	O
+hindbrain	O
+expression	O
+.	O
+
+AF154055	B-GENE
+.	O
+
+Alignment	O
+of	O
+the	O
+cervical	O
+spine	O
+,	O
+vertebral	O
+abnormalities	O
+,	O
+and	O
+disc	O
+changes	O
+also	O
+were	O
+evaluated	O
+.	O
+
+The	O
+concomitant	O
+interaction	O
+of	O
+mSTI1	B-GENE
+with	O
+hsp70	B-GENE
+and	O
+hsp90	B-GENE
+at	O
+its	O
+N	O
+-	O
+and	O
+C	O
+-	O
+termini	O
+respectively	O
+is	O
+mediated	O
+by	O
+the	O
+tetratricopeptide	O
+repeat	O
+(	O
+TPR	O
+)	O
+motifs	O
+in	O
+these	O
+regions	O
+.	O
+
+Competition	O
+experiments	O
+demonstrate	O
+a	O
+negative	O
+allosteric	O
+relationship	O
+between	O
+these	O
+RGD	O
+recognition	O
+sites	O
+.	O
+
+Sequence	O
+analysis	O
+showed	O
+that	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+upstream	O
+to	O
+the	O
+ATG	O
+codon	O
+did	O
+not	O
+contain	O
+a	O
+conventional	O
+TATA	O
+box	O
+.	O
+
+After	O
+i	O
+.	O
+v	O
+.	O
+administration	O
+of	O
+500	O
+mg	O
+acetazolamide	O
+and	O
+disinfection	O
+of	O
+the	O
+conjunctiva	O
+,	O
+50	O
+micrograms	O
+rt	B-GENE
+-	I-GENE
+PA	I-GENE
+in	O
+0	O
+.	O
+1	O
+ml	O
+(	O
+BSS	O
+)	O
+and	O
+0	O
+.	O
+5	O
+ml	O
+SF6	O
+were	O
+injected	O
+intravitreally	O
+.	O
+
+Differential	O
+expression	O
+and	O
+regulation	O
+by	O
+20	O
+-	O
+hydroxyecdysone	O
+of	O
+mosquito	O
+ultraspiracle	O
+isoforms	O
+.	O
+
+The	O
+three	O
+isoforms	O
+purified	O
+with	O
+anti	B-GENE
+-	I-GENE
+FLAG	I-GENE
+antibody	I-GENE
+affinity	O
+column	O
+transferred	O
+sulfate	O
+to	O
+heparan	O
+sulfate	O
+and	O
+heparin	O
+but	O
+not	O
+to	O
+other	O
+glycosaminoglycans	O
+.	O
+
+The	O
+differentiation	O
+and	O
+maintenance	O
+of	O
+a	O
+neurotransmitter	O
+phenotype	O
+is	O
+guided	O
+by	O
+the	O
+interaction	O
+of	O
+exogenous	O
+cues	O
+with	O
+intrinsic	O
+genetic	O
+machinery	O
+.	O
+
+Analysis	O
+of	O
+functional	O
+domains	O
+of	O
+Arix	B-GENE
+reveals	O
+an	O
+N	O
+-	O
+terminal	O
+activation	O
+domain	O
+and	O
+a	O
+C	O
+-	O
+terminal	O
+repression	O
+domain	O
+.	O
+
+BACKGROUND	O
+:	O
+Left	O
+ventricular	O
+hypertrophy	O
+is	O
+a	O
+heterogeneous	O
+disorder	O
+with	O
+distinct	O
+morphologies	O
+.	O
+
+Multivariate	O
+predictors	O
+were	O
+concentric	O
+remodeling	O
+(	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+;	O
+odds	O
+ratio	O
+,	O
+13	O
+.	O
+5	O
+)	O
+,	O
+left	O
+ventricular	O
+ejection	O
+fraction	O
+>	O
+2	O
+SD	O
+above	O
+normal	O
+(	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+,	O
+and	O
+single	O
+-	O
+vessel	O
+left	O
+circumflex	O
+disease	O
+(	O
+P	O
+<	O
+0	O
+.	O
+0007	O
+;	O
+odds	O
+ratio	O
+,	O
+7	O
+.	O
+6	O
+)	O
+.	O
+
+Overexpression	O
+of	O
+ICBP90	B-GENE
+in	O
+COS	O
+-	O
+1	O
+-	O
+transfected	O
+cells	O
+induced	O
+an	O
+enhanced	O
+expression	O
+of	O
+endogenous	B-GENE
+topoisomerase	I-GENE
+IIalpha	I-GENE
+.	O
+
+The	O
+RNA	O
+aptamer	O
+contains	O
+three	O
+stems	O
+separated	O
+by	O
+a	O
+pair	O
+of	O
+two	O
+-	O
+base	O
+bulges	O
+,	O
+and	O
+adopts	O
+an	O
+unanticipated	O
+fold	O
+in	O
+which	O
+both	O
+junctional	O
+sites	O
+are	O
+anchored	O
+through	O
+base	O
+triple	O
+formation	O
+.	O
+
+The	O
+study	O
+suggests	O
+the	O
+presence	O
+of	O
+an	O
+anatomical	O
+sphincter	O
+at	O
+the	O
+RSJ	O
+which	O
+seems	O
+to	O
+regulate	O
+the	O
+passage	O
+of	O
+stools	O
+from	O
+the	O
+sigmoid	O
+colon	O
+to	O
+the	O
+rectum	O
+.	O
+
+To	O
+quantify	O
+any	O
+mechanical	O
+inhibitory	O
+effect	O
+of	O
+nasal	O
+intermittent	O
+positive	O
+pressure	O
+ventilation	O
+(	O
+IPPV	O
+)	O
+on	O
+inspiratory	O
+activity	O
+of	O
+the	O
+diaphragm	O
+we	O
+ventilated	O
+five	O
+conscious	O
+relaxed	O
+subjects	O
+on	O
+two	O
+occasions	O
+at	O
+respiratory	O
+rates	O
+similar	O
+to	O
+quiet	O
+breathing	O
+(	O
+QB	O
+)	O
+and	O
+at	O
+three	O
+levels	O
+of	O
+applied	O
+pressure	O
+(	O
+Pappl	O
+)	O
+-	O
+-	O
+6	O
+,	O
+9	O
+and	O
+12	O
+cmH2O	O
+,	O
+each	O
+during	O
+hypocapnia	O
+(	O
+P	O
+(	O
+CO2	O
+)	O
+allowed	O
+to	O
+decrease	O
+)	O
+and	O
+eucapnia	O
+(	O
+CO2	O
+added	O
+to	O
+inspired	O
+gas	O
+)	O
+.	O
+
+METHODS	O
+:	O
+Von	B-GENE
+Willebrand	I-GENE
+factor	I-GENE
+(	O
+vWF	B-GENE
+)	O
+and	O
+the	O
+fibrinolytic	O
+factors	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+(	O
+tPA	B-GENE
+)	O
+,	O
+measured	O
+as	O
+tPA	B-GENE
+capacity	O
+,	O
+and	O
+plasminogen	B-GENE
+activator	I-GENE
+inhibitor	I-GENE
+1	I-GENE
+(	O
+PAI	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+platelets	O
+,	O
+fibrinogen	B-GENE
+,	O
+and	O
+inflammatory	O
+markers	O
+were	O
+measured	O
+in	O
+74	O
+patients	O
+with	O
+active	O
+seropositive	O
+RA	O
+.	O
+
+Neuronal	O
+signaling	O
+properties	O
+are	O
+largely	O
+determined	O
+by	O
+the	O
+quantity	O
+and	O
+combination	O
+of	O
+ion	O
+channels	O
+expressed	O
+.	O
+
+Treatment	O
+also	O
+led	O
+to	O
+a	O
+significant	O
+dose	O
+dependent	O
+reduction	O
+in	O
+the	O
+sum	O
+of	O
+ST	O
+segment	O
+depression	O
+at	O
+both	O
+trough	O
+and	O
+peak	O
+concentrations	O
+.	O
+
+We	O
+have	O
+investigated	O
+the	O
+contribution	O
+of	O
+specific	O
+TATA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+TBP	B-GENE
+)	O
+-	O
+TATA	O
+interactions	O
+to	O
+the	O
+promoter	O
+activity	O
+of	O
+a	O
+constitutively	O
+expressed	O
+silkworm	B-GENE
+tRNA	I-GENE
+(	I-GENE
+C	I-GENE
+)	I-GENE
+(	I-GENE
+Ala	I-GENE
+)	I-GENE
+gene	I-GENE
+and	O
+have	O
+also	O
+asked	O
+whether	O
+the	O
+lack	O
+of	O
+similar	O
+interactions	O
+accounts	O
+for	O
+the	O
+low	O
+promoter	O
+activity	O
+of	O
+a	O
+silk	B-GENE
+gland	I-GENE
+-	I-GENE
+specific	I-GENE
+tRNA	I-GENE
+(	I-GENE
+SG	I-GENE
+)	I-GENE
+(	I-GENE
+Ala	I-GENE
+)	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+sequences	O
+showed	O
+extensive	O
+homologies	O
+with	O
+squalene	B-GENE
+synthase	I-GENE
+genes	I-GENE
+and	O
+enzymes	O
+from	O
+a	O
+number	O
+of	O
+other	O
+organisms	O
+and	O
+extreme	O
+amino	O
+acid	O
+conservation	O
+within	O
+the	O
+binding	O
+and	O
+catalytic	O
+domains	O
+.	O
+
+Two	O
+episodes	O
+of	O
+peritonitis	O
+occurred	O
+while	O
+the	O
+patient	O
+received	O
+CAPD	O
+(	O
+1	O
+episode	O
+/	O
+3	O
+.	O
+5	O
+patient	O
+-	O
+months	O
+)	O
+.	O
+
+Copyright	O
+2000	O
+The	O
+Royal	O
+College	O
+of	O
+Radiologists	O
+.	O
+
+Two	O
+estrogen	B-GENE
+receptor	I-GENE
+(	O
+ER	B-GENE
+)	O
+isoforms	O
+with	O
+different	O
+estrogen	O
+dependencies	O
+are	O
+generated	O
+from	O
+the	O
+trout	B-GENE
+ER	I-GENE
+gene	I-GENE
+.	O
+
+Induction	O
+was	O
+reversed	O
+by	O
+coexpression	O
+of	O
+A	B-GENE
+-	I-GENE
+Fos	I-GENE
+,	O
+a	O
+dominant	O
+negative	O
+to	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+In	O
+myometrial	O
+SMC	O
+,	O
+both	O
+isoforms	O
+of	O
+the	O
+progesterone	B-GENE
+receptor	I-GENE
+,	O
+PR	B-GENE
+-	I-GENE
+B	I-GENE
+and	O
+PR	B-GENE
+-	I-GENE
+A	I-GENE
+,	O
+caused	O
+a	O
+ligand	O
+-	O
+dependent	O
+activation	O
+of	O
+PGDH	B-GENE
+-	I-GENE
+2368	I-GENE
+/	O
+luc3	B-GENE
+.	O
+
+Element	O
+B	O
+(	O
+-	O
+249	O
+/	O
+-	O
+229	O
+)	O
+shows	O
+more	O
+than	O
+80	O
+%	O
+homology	O
+to	O
+a	O
+consensus	B-GENE
+c	I-GENE
+-	I-GENE
+myb	I-GENE
+element	I-GENE
+,	O
+but	O
+formed	O
+two	O
+specific	O
+complexes	O
+that	O
+differed	O
+from	O
+that	O
+of	O
+c	B-GENE
+-	I-GENE
+myb	I-GENE
+in	O
+the	O
+electrophoretic	O
+mobility	O
+shift	O
+assay	O
+.	O
+
+Stable	O
+transfection	O
+of	O
+the	O
+truncated	O
+reduced	B-GENE
+folate	I-GENE
+carrier	I-GENE
+cDNA	I-GENE
+into	O
+mouse	O
+L1210	O
+leukemia	O
+cells	O
+:	O
+increased	O
+folate	O
+accumulation	O
+,	O
+decreased	O
+their	O
+leucovorin	O
+and	O
+folic	O
+acid	O
+growth	O
+requirements	O
+,	O
+and	O
+increased	O
+their	O
+sensitivity	O
+to	O
+methotrexate	O
+.	O
+
+Characterization	O
+of	O
+a	O
+human	B-GENE
+alternatively	I-GENE
+spliced	I-GENE
+truncated	I-GENE
+reduced	I-GENE
+folate	I-GENE
+carrier	I-GENE
+increasing	O
+folate	O
+accumulation	O
+in	O
+parental	O
+leukemia	O
+cells	O
+.	O
+
+Electron	O
+microscopic	O
+and	O
+enzymatic	O
+analyses	O
+revealed	O
+that	O
+the	O
+A118	O
+genome	O
+is	O
+a	O
+linear	O
+,	O
+circularly	O
+permuted	O
+,	O
+terminally	O
+redundant	O
+collection	O
+of	O
+double	O
+-	O
+stranded	O
+DNA	O
+molecules	O
+.	O
+
+Moreover	O
+,	O
+increasing	O
+the	O
+dosage	O
+of	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+Fus3	I-GENE
+intensifies	O
+the	O
+inhibition	O
+of	O
+both	O
+Ty1	B-GENE
+transposition	O
+and	O
+invasive	O
+growth	O
+.	O
+
+Consistently	O
+,	O
+activation	O
+of	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+downstream	O
+of	O
+Rho	B-GENE
+family	I-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+was	O
+also	O
+enhanced	O
+when	O
+Dbl	B-GENE
+was	O
+tyrosine	O
+-	O
+phosphorylated	O
+.	O
+
+However	O
+,	O
+its	O
+participation	O
+in	O
+collagen	B-GENE
+binding	O
+has	O
+not	O
+been	O
+shown	O
+.	O
+
+Together	O
+,	O
+these	O
+data	O
+suggest	O
+that	O
+the	O
+carboxyl	O
+terminus	O
+of	O
+CFTR	B-GENE
+contains	O
+a	O
+tyrosine	O
+-	O
+based	O
+internalization	O
+signal	O
+that	O
+interacts	O
+with	O
+the	O
+endocytic	O
+adaptor	O
+complex	O
+AP	B-GENE
+-	I-GENE
+2	I-GENE
+to	O
+facilitate	O
+efficient	O
+entry	O
+of	O
+CFTR	B-GENE
+into	O
+clathrin	B-GENE
+-	O
+coated	O
+vesicles	O
+.	O
+
+The	O
+insulin	B-GENE
+therapy	O
+regimen	O
+did	O
+not	O
+affect	O
+the	O
+evolution	O
+of	O
+the	O
+patients	O
+and	O
+no	O
+significant	O
+relationship	O
+existed	O
+between	O
+the	O
+age	O
+at	O
+diagnosis	O
+,	O
+duration	O
+of	O
+diabetes	O
+,	O
+daily	O
+insulin	B-GENE
+dosage	O
+or	O
+metabolic	O
+control	O
+and	O
+height	O
+or	O
+BMI	O
+.	O
+
+Scmh1	B-GENE
+maps	O
+to	O
+4D1	O
+-	O
+D2	O
+.	O
+1	O
+in	O
+mice	O
+.	O
+
+The	O
+applicability	O
+of	O
+laparoscopic	O
+donor	O
+nephrectomy	O
+(	O
+LDN	O
+)	O
+has	O
+not	O
+been	O
+assessed	O
+in	O
+the	O
+obese	O
+donor	O
+.	O
+
+Hyaluronan	O
+treatment	O
+stimulated	O
+collagen	B-GENE
+remodeling	O
+in	O
+the	O
+peripheral	O
+region	O
+and	O
+inhibited	O
+swelling	O
+of	O
+the	O
+meniscus	O
+repaired	O
+in	O
+the	O
+inner	O
+region	O
+.	O
+
+We	O
+have	O
+addressed	O
+these	O
+issues	O
+by	O
+reconstituting	O
+and	O
+characterizing	O
+the	O
+KRAB	B-GENE
+:	O
+KAP	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+RBCC	B-GENE
+interaction	O
+using	O
+purified	O
+components	O
+.	O
+
+The	O
+RING	O
+finger	O
+,	O
+B2	O
+box	O
+,	O
+and	O
+coiled	O
+-	O
+coil	O
+region	O
+are	O
+required	O
+for	O
+oligomerization	O
+of	O
+KAP	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+RBCC	B-GENE
+and	O
+KRAB	B-GENE
+binding	O
+,	O
+as	O
+mutations	O
+in	O
+these	O
+domains	O
+concomitantly	O
+abolished	O
+these	O
+functions	O
+.	O
+
+JPEG	O
+53	O
+,	O
+resulting	O
+in	O
+a	O
+compression	O
+ratio	O
+of	O
+1	O
+:	O
+21	O
+,	O
+does	O
+not	O
+compromise	O
+the	O
+diagnostic	O
+performance	O
+in	O
+general	O
+.	O
+
+We	O
+critically	O
+assess	O
+current	O
+systematic	O
+uncertainties	O
+and	O
+determine	O
+the	O
+primordial	O
+Li	O
+abundance	O
+within	O
+new	O
+,	O
+much	O
+tighter	O
+limits	O
+:	O
+&	O
+amp	O
+;	O
+parl0	O
+;	O
+Li	O
+&	O
+amp	O
+;	O
+solm0	O
+;	O
+H	O
+&	O
+amp	O
+;	O
+parr0	O
+;	O
+p	O
+=	O
+1	O
+.	O
+23	O
++	O
+0	O
+.	O
+68	O
+-	O
+0	O
+.	O
+32x10	O
+-	O
+10	O
+.	O
+
+Like	O
+their	O
+yeast	O
+counterpart	O
+,	O
+the	O
+mouse	O
+GCN2	B-GENE
+isoforms	O
+contain	O
+HisRS	B-GENE
+-	I-GENE
+related	I-GENE
+sequences	I-GENE
+juxtaposed	O
+to	O
+the	O
+kinase	O
+catalytic	O
+domain	O
+.	O
+
+Five	O
+women	O
+(	O
+15	O
+.	O
+6	O
+%	O
+)	O
+met	O
+criteria	O
+for	O
+PMS	O
+.	O
+
+MBI	O
+and	O
+MMBI	O
+showed	O
+similar	O
+Cmax	O
+values	O
+,	O
+but	O
+the	O
+former	O
+disappeared	O
+slower	O
+in	O
+the	O
+serum	O
+than	O
+the	O
+latter	O
+and	O
+resulted	O
+in	O
+its	O
+larger	O
+AUC	O
+values	O
+.	O
+
+Another	O
+long	O
+insertion	O
+in	O
+the	O
+cathepsin	B-GENE
+X	I-GENE
+amino	I-GENE
+acid	I-GENE
+sequence	I-GENE
+forms	O
+a	O
+beta	O
+-	O
+hairpin	O
+pointing	O
+away	O
+from	O
+the	O
+active	O
+site	O
+.	O
+
+Transfection	O
+experiments	O
+demonstrated	O
+that	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+(	O
+-	O
+1894	O
+to	O
++	O
+37	O
+)	O
+of	O
+the	O
+mStaf	B-GENE
+gene	I-GENE
+drives	O
+transcription	O
+in	O
+mouse	O
+NMuMG	O
+cells	O
+and	O
+that	O
+a	O
+construct	O
+containing	O
+a	O
+fragment	O
+from	O
+-	O
+387	O
+to	O
++	O
+37	O
+showed	O
+the	O
+highest	O
+transcriptional	O
+activity	O
+.	O
+
+Further	O
+studies	O
+in	O
+T	O
+-	O
+24	O
+cells	O
+demonstrated	O
+that	O
+HA	O
+fragments	O
+also	O
+induced	O
+I	B-GENE
+kappa	I-GENE
+B	I-GENE
+alpha	I-GENE
+phosphorylation	O
+and	O
+degradation	O
+,	O
+kappa	B-GENE
+B	I-GENE
+-	I-GENE
+linked	I-GENE
+reporter	I-GENE
+gene	I-GENE
+expression	O
+,	O
+and	O
+ICAM	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+activity	O
+in	O
+an	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+-	O
+dependent	O
+manner	O
+.	O
+
+Pretreatment	O
+of	O
+cells	O
+or	O
+mouse	O
+skin	O
+with	O
+antisense	O
+oligonucleotides	O
+of	O
+PKCzeta	B-GENE
+impaired	O
+UV	O
+-	O
+induced	O
+activation	O
+of	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+JB6	O
+cells	O
+as	O
+well	O
+as	O
+in	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+luciferase	B-GENE
+transgenic	O
+mice	O
+.	O
+
+The	O
+level	O
+of	O
+subclinical	O
+infection	O
+was	O
+75	O
+%	O
+among	O
+seropositive	O
+dogs	O
+.	O
+
+Desmethylferrochloroquine	O
+1a	O
+and	O
+didesmethylferrochloroquine	O
+2	O
+would	O
+be	O
+more	O
+potent	O
+against	O
+schizontocides	O
+than	O
+CQ	O
+in	O
+vitro	O
+against	O
+two	O
+strains	O
+(	O
+HB3	O
+and	O
+Dd2	O
+)	O
+of	O
+Plasmodium	O
+falciparum	O
+.	O
+
+The	O
+rrd1	B-GENE
+,	I-GENE
+2delta	I-GENE
+mutant	I-GENE
+was	O
+partially	O
+rescued	O
+by	O
+inactivation	O
+of	O
+HOG1	B-GENE
+or	O
+PBS2	B-GENE
+,	O
+suggesting	O
+an	O
+interaction	O
+between	O
+the	O
+RRD	B-GENE
+genes	I-GENE
+and	O
+the	O
+Hog1p	B-GENE
+signal	I-GENE
+transduction	I-GENE
+pathway	I-GENE
+.	O
+
+Members	O
+of	O
+the	O
+JAK	B-GENE
+/	O
+Tyk	B-GENE
+family	O
+of	O
+tyrosine	B-GENE
+kinases	I-GENE
+mediate	O
+phosphorylation	O
+of	O
+STAT3	B-GENE
+at	O
+Tyr705	O
+during	O
+CNTF	B-GENE
+signaling	O
+;	O
+however	O
+,	O
+the	O
+kinase	O
+responsible	O
+for	O
+phosphorylation	O
+at	O
+STAT3	B-GENE
+Tyr727	O
+appears	O
+to	O
+depend	O
+on	O
+both	O
+the	O
+extracellular	O
+stimulus	O
+and	O
+the	O
+cellular	O
+context	O
+.	O
+
+In	O
+vivo	O
+,	O
+CARbeta	B-GENE
+/	O
+RXRalpha	B-GENE
+activated	O
+transcription	O
+from	O
+an	O
+HD	B-GENE
+-	O
+PPRE	O
+luciferase	B-GENE
+reporter	I-GENE
+construct	I-GENE
+.	O
+
+Thus	O
+,	O
+SOX8	B-GENE
+is	O
+a	O
+good	O
+candidate	O
+gene	O
+contributing	O
+to	O
+the	O
+mental	O
+retardation	O
+phenotype	O
+seen	O
+in	O
+ATR	O
+-	O
+16	O
+patients	O
+.	O
+
+Patch	O
+test	O
+results	O
+obtained	O
+with	O
+corticosteroid	O
+allergic	O
+patients	O
+tested	O
+with	O
+a	O
+large	O
+corticosteroid	O
+series	O
+validated	O
+the	O
+earlier	O
+classification	O
+of	O
+corticosteroid	O
+molecules	O
+in	O
+four	O
+groups	O
+of	O
+cross	O
+-	O
+reacting	O
+molecules	O
+:	O
+i	O
+.	O
+e	O
+.	O
+,	O
+group	O
+A	O
+(	O
+hydrocortisone	O
+type	O
+)	O
+,	O
+group	O
+B	O
+(	O
+acetonides	O
+)	O
+,	O
+group	O
+C	O
+(	O
+betamethasone	O
+type	O
+-	O
+non	O
+esterified	O
+)	O
+and	O
+group	O
+D	O
+(	O
+esters	O
+)	O
+.	O
+
+An	O
+increase	O
+in	O
+the	O
+level	O
+of	O
+serum	O
+enzymes	O
+,	O
+such	O
+as	O
+aspartate	B-GENE
+transaminase	I-GENE
+,	O
+alkaline	B-GENE
+phosphatase	I-GENE
+,	O
+creatine	B-GENE
+phosphokinase	I-GENE
+,	O
+lactate	B-GENE
+dehydrogenase	I-GENE
+after	O
+D	O
+.	O
+russelli	O
+venom	O
+injection	O
+in	O
+albino	O
+rats	O
+is	O
+indicative	O
+of	O
+cell	O
+or	O
+tissue	O
+damage	O
+.	O
+
+The	O
+partial	O
+farm	O
+budget	O
+highlighted	O
+the	O
+importance	O
+of	O
+reducing	O
+sub	O
+-	O
+clinical	O
+lesions	O
+in	O
+a	O
+feedlot	O
+.	O
+
+Surprisingly	O
+,	O
+3	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+murine	I-GENE
+survivin	I-GENE
+cDNA	I-GENE
+clones	O
+were	O
+isolated	O
+,	O
+predicting	O
+the	O
+existence	O
+of	O
+3	O
+distinct	O
+survivin	B-GENE
+proteins	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+induction	O
+of	O
+E2F	B-GENE
+binding	O
+to	O
+the	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+by	O
+the	O
+E4	B-GENE
+-	I-GENE
+6	I-GENE
+/	I-GENE
+7	I-GENE
+protein	I-GENE
+observed	O
+in	O
+vitro	O
+correlates	O
+with	O
+transactivation	O
+of	O
+E2F	B-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+activity	O
+in	O
+vivo	O
+.	O
+
+We	O
+show	O
+that	O
+stabilization	O
+of	O
+the	O
+hairpin	O
+reduced	O
+the	O
+amount	O
+of	O
+tRNA	O
+primer	O
+that	O
+is	O
+annealed	O
+to	O
+the	O
+PBS	O
+.	O
+
+Ischemia	O
+-	O
+induced	O
+biphasic	O
+arrhythmias	O
+were	O
+suppressed	O
+in	O
+both	O
+zatebradine	O
+and	O
+propranolol	O
+groups	O
+.	O
+
+ZK7	B-GENE
+and	O
+HZF16	B-GENE
+genes	I-GENE
+appear	O
+to	O
+be	O
+the	O
+splice	O
+variants	O
+transcribed	O
+from	O
+the	O
+same	O
+gene	O
+.	O
+
+CONCLUSION	O
+:	O
+Presence	O
+of	O
+APOE	B-GENE
+epsilon4	I-GENE
+/	I-GENE
+*	I-GENE
+seems	O
+to	O
+increase	O
+the	O
+risk	O
+for	O
+dementia	O
+and	O
+AD	O
+independently	O
+of	O
+its	O
+effect	O
+on	O
+dyslipidemia	O
+and	O
+atherogenesis	O
+.	O
+
+No	O
+definite	O
+conclusions	O
+are	O
+possible	O
+because	O
+of	O
+the	O
+small	O
+number	O
+of	O
+patients	O
+involved	O
+in	O
+this	O
+phase	O
+II	O
+trial	O
+.	O
+
+Two	O
+distinct	O
+Salmonella	B-GENE
+fimbrins	I-GENE
+,	O
+AgfA	B-GENE
+and	O
+SefA	B-GENE
+,	O
+comprising	O
+thin	O
+aggregative	O
+fimbriae	O
+SEF17	B-GENE
+and	O
+SEF14	B-GENE
+,	O
+respectively	O
+,	O
+were	O
+each	O
+genetically	O
+engineered	O
+to	O
+carry	O
+PT3	B-GENE
+,	O
+an	O
+alpha	O
+-	O
+helical	O
+16	O
+-	O
+amino	O
+acid	O
+Leishmania	O
+T	O
+-	O
+cell	O
+epitope	O
+derived	O
+from	O
+the	O
+metalloprotease	B-GENE
+gp63	B-GENE
+.	O
+
+In	O
+marked	O
+contrast	O
+to	O
+AgfA	B-GENE
+,	O
+none	O
+of	O
+the	O
+chimeric	B-GENE
+SefA	I-GENE
+proteins	I-GENE
+were	O
+expressed	O
+or	O
+assembled	O
+into	O
+fimbriae	O
+.	O
+
+Productive	O
+growth	O
+of	O
+phage	O
+P22	O
+in	O
+wild	O
+-	O
+type	O
+Salmonella	O
+typhimurium	O
+correlates	O
+with	O
+the	O
+presence	O
+of	O
+Abc2	B-GENE
+,	O
+but	O
+is	O
+independent	O
+of	O
+the	O
+absolute	O
+level	O
+of	O
+ATP	B-GENE
+-	I-GENE
+dependent	I-GENE
+nuclease	I-GENE
+activity	O
+,	O
+suggesting	O
+a	O
+qualitative	O
+change	O
+in	O
+the	O
+nature	O
+of	O
+Abc2	B-GENE
+-	O
+modified	O
+RecBCD	B-GENE
+nuclease	I-GENE
+activity	O
+relative	O
+to	O
+the	O
+native	O
+enzyme	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+investigated	O
+the	O
+molecular	O
+mechanisms	O
+underlying	O
+the	O
+inducible	O
+expression	O
+of	O
+the	O
+flt	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+during	O
+the	O
+activation	O
+of	O
+THP	O
+-	O
+1	O
+cells	O
+.	O
+
+There	O
+was	O
+a	O
+2	O
+.	O
+4	O
+-	O
+fold	O
+difference	O
+in	O
+CAT	B-GENE
+produced	O
+from	O
+these	O
+transcripts	O
+in	O
+HeLa	O
+cells	O
+,	O
+which	O
+contain	O
+a	O
+greater	O
+natural	O
+abundance	O
+of	O
+PTB	B-GENE
+.	O
+
+Multiple	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+signaling	O
+pathways	O
+connect	O
+the	O
+cot	B-GENE
+oncoprotein	I-GENE
+to	O
+the	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+promoter	I-GENE
+and	O
+to	O
+cellular	O
+transformation	O
+.	O
+
+4	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+we	O
+have	O
+investigated	O
+the	O
+regulatory	O
+mechanism	O
+for	O
+CD95L	B-GENE
+expression	O
+.	O
+
+Protein	O
+sequence	O
+analysis	O
+reveals	O
+that	O
+MAN1	B-GENE
+shares	O
+a	O
+conserved	O
+globular	O
+domain	O
+of	O
+approximately	O
+40	O
+amino	O
+acids	O
+,	O
+which	O
+we	O
+term	O
+the	O
+LEM	B-GENE
+module	I-GENE
+,	O
+with	O
+inner	O
+nuclear	O
+membrane	O
+proteins	O
+lamina	B-GENE
+-	I-GENE
+associated	I-GENE
+polypeptide	I-GENE
+2	I-GENE
+and	O
+emerin	B-GENE
+.	O
+
+The	O
+encoded	O
+amino	O
+acid	O
+sequences	O
+in	O
+the	O
+full	O
+-	O
+length	O
+bovine	O
+and	O
+porcine	O
+cDNAs	O
+were	O
+identical	O
+,	O
+consisting	O
+of	O
+209	O
+amino	O
+acid	O
+residues	O
+,	O
+and	O
+were	O
+nearly	O
+the	O
+same	O
+as	O
+the	O
+published	O
+sequence	O
+determined	O
+by	O
+Edman	O
+degradation	O
+.	O
+
+With	O
+chemical	O
+shift	O
+imaging	O
+,	O
+the	O
+signal	O
+intensity	O
+decreased	O
+on	O
+the	O
+out	O
+-	O
+of	O
+-	O
+phase	O
+images	O
+in	O
+six	O
+of	O
+seven	O
+(	O
+86	O
+%	O
+)	O
+patients	O
+with	O
+APA	O
+and	O
+in	O
+eight	O
+of	O
+nine	O
+(	O
+89	O
+%	O
+)	O
+patients	O
+with	O
+BAH	O
+.	O
+
+For	O
+each	O
+night	O
+,	O
+the	O
+diary	O
+allowed	O
+the	O
+subjective	O
+measurement	O
+of	O
+bedtime	O
+,	O
+wake	O
+time	O
+,	O
+time	O
+in	O
+bed	O
+(	O
+TIB	O
+)	O
+,	O
+sleep	O
+efficiency	O
+,	O
+number	O
+of	O
+minutes	O
+of	O
+wake	O
+after	O
+sleep	O
+onset	O
+(	O
+WASO	O
+)	O
+,	O
+alertness	O
+on	O
+awakening	O
+,	O
+and	O
+percentage	O
+of	O
+morning	O
+needing	O
+an	O
+alarm	O
+(	O
+or	O
+a	O
+person	O
+functioning	O
+as	O
+one	O
+)	O
+.	O
+
+Acad	O
+.	O
+
+Copyright	O
+2000	O
+Academic	O
+Press	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+combined	O
+lesions	O
+of	O
+cholinergic	O
+and	O
+serotonergic	O
+neurons	O
+in	O
+the	O
+rat	O
+brain	O
+do	O
+not	O
+alter	O
+olfactory	O
+perception	O
+or	O
+olfactory	O
+short	O
+-	O
+term	O
+memory	O
+.	O
+
+Extreme	O
+potency	O
+of	O
+botulinum	B-GENE
+toxin	I-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+c	B-GENE
+-	I-GENE
+Src	I-GENE
+activated	O
+by	O
+isoproterenol	O
+led	O
+to	O
+tyrosine	O
+phosphorylation	O
+of	O
+Shc	B-GENE
+and	O
+subsequent	O
+Erk	B-GENE
+activation	O
+,	O
+but	O
+not	O
+tyrosine	O
+phosphorylation	O
+of	O
+cortactin	B-GENE
+or	O
+Stat3	B-GENE
+.	O
+
+For	O
+wild	O
+type	O
+MutT	B-GENE
+and	O
+its	O
+E53D	B-GENE
+and	O
+E44D	B-GENE
+mutants	I-GENE
+,	O
+plots	O
+of	O
+log	O
+(	O
+k	O
+(	O
+cat	O
+)	O
+)	O
+versus	O
+pH	O
+exhibited	O
+a	O
+limiting	O
+slope	O
+of	O
+1	O
+on	O
+the	O
+ascending	O
+limb	O
+and	O
+then	O
+a	O
+hump	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+a	O
+sharply	O
+defined	O
+maximum	O
+near	O
+pH	O
+8	O
+followed	O
+by	O
+a	O
+plateau	O
+,	O
+yielding	O
+apparent	O
+pK	O
+(	O
+a	O
+)	O
+values	O
+of	O
+7	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+3	O
+and	O
+8	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+4	O
+for	O
+an	O
+essential	O
+base	O
+and	O
+a	O
+nonessential	O
+acid	O
+catalyst	O
+,	O
+respectively	O
+,	O
+in	O
+the	O
+active	O
+quaternary	O
+MutT	B-GENE
+-	O
+Mg	O
+(	O
+2	O
++	O
+)	O
+-	O
+dGTP	O
+-	O
+Mg	O
+(	O
+2	O
++	O
+)	O
+complex	O
+.	O
+
+Structural	O
+changes	O
+in	O
+the	O
+kinetically	O
+more	O
+damaged	O
+E44D	O
+mutant	O
+detected	O
+in	O
+(	O
+1	O
+)	O
+H	O
+-	O
+(	O
+15	O
+)	O
+N	O
+HSQC	O
+spectra	O
+were	O
+largely	O
+limited	O
+to	O
+the	O
+loop	O
+I	O
+-	O
+helix	O
+I	O
+motif	O
+,	O
+suggesting	O
+that	O
+Glu	O
+-	O
+44	O
+stabilizes	O
+the	O
+active	O
+site	O
+region	O
+.	O
+
+In	O
+vitro	O
+expression	O
+of	O
+four	O
+different	O
+naturally	O
+occurring	O
+nonsense	O
+and	O
+missense	O
+mutations	O
+revealed	O
+a	O
+dramatically	O
+altered	O
+subcellular	O
+location	O
+of	O
+the	O
+protein	O
+in	O
+cultured	O
+cells	O
+.	O
+
+After	O
+i	O
+.	O
+v	O
+.	O
+
+Immunity	O
+acquired	O
+by	O
+mice	O
+during	O
+I	O
+.	O
+scapularis	O
+nymphal	O
+activity	O
+in	O
+early	O
+summer	O
+may	O
+exclude	O
+a	O
+large	O
+proportion	O
+of	O
+the	O
+mouse	O
+population	O
+from	O
+maintaining	O
+E	O
+.	O
+phagocytophila	O
+during	O
+the	O
+period	O
+of	O
+larval	O
+activity	O
+later	O
+in	O
+the	O
+season	O
+.	O
+
+The	O
+emerging	O
+view	O
+based	O
+on	O
+studies	O
+in	O
+yeast	O
+is	O
+that	O
+each	O
+class	O
+of	O
+snoRNPs	O
+is	O
+composed	O
+of	O
+a	O
+unique	O
+set	O
+of	O
+proteins	O
+.	O
+
+BCR	B-GENE
+cross	O
+-	O
+linking	O
+also	O
+led	O
+to	O
+increased	O
+MAPK	B-GENE
+-	O
+activated	O
+protein	B-GENE
+kinase	I-GENE
+-	I-GENE
+2	I-GENE
+activity	O
+,	O
+an	O
+enzyme	O
+that	O
+lies	O
+immediately	O
+downstream	O
+from	O
+p38	B-GENE
+MAPK	I-GENE
+;	O
+MAPK	B-GENE
+-	O
+activated	O
+protein	B-GENE
+kinase	I-GENE
+-	I-GENE
+2	I-GENE
+immune	O
+complexes	O
+phosphorylated	O
+a	O
+peptide	O
+substrate	O
+containing	O
+the	O
+CREB	B-GENE
+serine	I-GENE
+133	I-GENE
+phosphoacceptor	I-GENE
+motif	I-GENE
+.	O
+
+Activation	O
+of	O
+a	O
+CRE	O
+-	O
+dependent	O
+junB	B-GENE
+promoter	I-GENE
+/	O
+chloramphenicol	B-GENE
+acetyltransferase	I-GENE
+(	O
+CAT	B-GENE
+)	O
+reporter	O
+gene	O
+by	O
+the	O
+BCR	B-GENE
+was	O
+also	O
+blocked	O
+by	O
+SB203580	O
+.	O
+
+We	O
+present	O
+evidence	O
+that	O
+the	O
+upstream	O
+open	O
+reading	O
+frame	O
+(	O
+uORF	O
+)	O
+represses	O
+the	O
+translation	O
+of	O
+the	O
+downstream	O
+major	O
+open	O
+reading	O
+frame	O
+(	O
+mORF	O
+)	O
+.	O
+
+METHODS	O
+:	O
+TBN	O
+measurements	O
+were	O
+performed	O
+in	O
+31	O
+female	O
+outpatients	O
+with	O
+breast	O
+carcinoma	O
+who	O
+were	O
+undergoing	O
+standard	O
+cyclophosphamide	O
+,	O
+methotrexate	O
+,	O
+and	O
+5	O
+-	O
+fluorouracil	O
+(	O
+CMF	O
+)	O
+-	O
+based	O
+chemotherapy	O
+(	O
+median	O
+age	O
+,	O
+48	O
+years	O
+;	O
+range	O
+,	O
+26	O
+-	O
+77	O
+years	O
+)	O
+.	O
+
+A	O
+385	O
+bp	O
+Glucocorticoid	O
+Response	O
+Unit	O
+(	O
+GRU	O
+)	O
+was	O
+identified	O
+whose	O
+glucocorticoid	O
+induction	O
+was	O
+enhanced	O
+by	O
+dibutyryl	O
+-	O
+cAMP	O
+and	O
+reduced	O
+by	O
+phorbol	O
+esters	O
+.	O
+
+No	O
+somatic	O
+mutations	O
+were	O
+found	O
+in	O
+any	O
+of	O
+the	O
+samples	O
+,	O
+suggesting	O
+that	O
+ING1	B-GENE
+is	O
+not	O
+a	O
+tumor	O
+suppressor	O
+gene	O
+target	O
+in	O
+head	O
+and	O
+neck	O
+cancer	O
+.	O
+
+Ras	B-GENE
+-	O
+GRF1	B-GENE
+transiently	O
+expressed	O
+with	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+was	O
+tyrosine	O
+-	O
+phosphorylated	O
+and	O
+showed	O
+significant	O
+GEF	B-GENE
+activity	O
+toward	O
+Rac	B-GENE
+,	O
+but	O
+not	O
+Rho	B-GENE
+and	O
+Cdc42	B-GENE
+,	O
+which	O
+was	O
+comparable	O
+with	O
+that	O
+induced	O
+by	O
+Gbetagamma	B-GENE
+.	O
+
+EMSA	O
+showed	O
+that	O
+nuclear	O
+proteins	O
+from	O
+PC12	O
+but	O
+not	O
+C6	O
+or	O
+Rat2	O
+cells	O
+bind	O
+the	O
+CRE	O
+as	O
+a	O
+complex	O
+containing	O
+activating	B-GENE
+transcription	I-GENE
+factor	I-GENE
+(	I-GENE
+ATF	I-GENE
+)	I-GENE
+-	I-GENE
+4	I-GENE
+and	O
+CCAAT	B-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+beta	I-GENE
+,	O
+while	O
+both	O
+PC12	O
+and	O
+C6	O
+cell	O
+nuclear	O
+extracts	O
+were	O
+recruited	O
+by	O
+the	O
+CCAAT	O
+-	O
+box	O
+as	O
+a	O
+complex	O
+containing	O
+nuclear	B-GENE
+factor	I-GENE
+Y	I-GENE
+.	O
+
+EMSA	O
+showed	O
+that	O
+nuclear	O
+proteins	O
+from	O
+PC12	O
+but	O
+not	O
+C6	O
+or	O
+Rat2	O
+cells	O
+bind	O
+the	O
+CRE	O
+as	O
+a	O
+complex	O
+containing	O
+activating	B-GENE
+transcription	I-GENE
+factor	I-GENE
+(	I-GENE
+ATF	I-GENE
+)	I-GENE
+-	I-GENE
+4	I-GENE
+and	O
+CCAAT	B-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+beta	I-GENE
+,	O
+while	O
+both	O
+PC12	O
+and	O
+C6	O
+cell	O
+nuclear	O
+extracts	O
+were	O
+recruited	O
+by	O
+the	O
+CCAAT	O
+-	O
+box	O
+as	O
+a	O
+complex	O
+containing	O
+nuclear	B-GENE
+factor	I-GENE
+Y	I-GENE
+.	O
+
+Despite	O
+resolution	O
+of	O
+the	O
+solid	O
+portion	O
+of	O
+the	O
+tumor	O
+,	O
+serial	O
+MRI	O
+showed	O
+enlargement	O
+of	O
+a	O
+bilobar	O
+tumor	O
+cyst	O
+3	O
+years	O
+after	O
+the	O
+original	O
+diagnosis	O
+.	O
+
+LPO	O
+and	O
+SOD	B-GENE
+levels	O
+were	O
+measured	O
+at	O
+five	O
+points	O
+before	O
+and	O
+during	O
+the	O
+operation	O
+.	O
+
+Sustained	O
+ventricular	O
+tachycardia	O
+and	O
+its	O
+successful	O
+prophylaxis	O
+during	O
+high	O
+-	O
+dose	O
+bolus	O
+interleukin	B-GENE
+-	I-GENE
+2	I-GENE
+therapy	O
+for	O
+metastatic	O
+renal	O
+cell	O
+carcinoma	O
+.	O
+
+Second	O
+,	O
+when	O
+the	O
+NBF1	B-GENE
++	I-GENE
+R	I-GENE
+protein	I-GENE
+,	O
+the	O
+NBF2	B-GENE
+protein	I-GENE
+,	O
+and	O
+a	O
+mixture	O
+of	O
+the	O
+two	O
+proteins	O
+were	O
+folded	O
+separately	O
+and	O
+analyzed	O
+by	O
+molecular	O
+sieve	O
+chomatography	O
+,	O
+the	O
+mixture	O
+was	O
+found	O
+to	O
+elute	O
+prior	O
+to	O
+either	O
+NBF1	B-GENE
++	I-GENE
+R	I-GENE
+or	O
+NBF2	B-GENE
+.	O
+
+Collectively	O
+,	O
+these	O
+experiments	O
+demonstrate	O
+that	O
+CFTR	B-GENE
+'	I-GENE
+s	I-GENE
+NBF1	I-GENE
++	I-GENE
+R	I-GENE
+region	I-GENE
+and	O
+its	O
+NBF2	B-GENE
+domain	I-GENE
+,	O
+after	O
+folding	O
+separately	O
+as	O
+distinct	O
+units	O
+,	O
+have	O
+a	O
+strong	O
+propensity	O
+to	O
+interact	O
+and	O
+that	O
+this	O
+interaction	O
+is	O
+stable	O
+in	O
+the	O
+absence	O
+of	O
+added	O
+nucleotides	O
+or	O
+exogenously	O
+induced	O
+phosphorylation	O
+.	O
+
+Copyright	O
+2000	O
+Academic	O
+Press	O
+.	O
+
+Sulfhydryl	O
+titration	O
+with	O
+iodoacetamide	O
+,	O
+monitored	O
+by	O
+quantitating	O
+the	O
+residual	O
+thiols	O
+after	O
+reaction	O
+with	O
+a	O
+maleimide	O
+derivative	O
+of	O
+biotin	O
+,	O
+revealed	O
+a	O
+striking	O
+difference	O
+in	O
+the	O
+apparent	O
+pK	O
+(	O
+a	O
+)	O
+values	O
+of	O
+the	O
+cysteines	O
+at	O
+the	O
+two	O
+splice	O
+junctions	O
+.	O
+
+After	O
+nitric	O
+oxide	O
+inhalation	O
+,	O
+the	O
+results	O
+showed	O
+moderate	O
+increases	O
+in	O
+PaO2	O
+and	O
+SaO2	O
+(	O
+P	O
+>	O
+0	O
+.	O
+05	O
+)	O
+and	O
+a	O
+significant	O
+decrease	O
+in	O
+Qs	O
+/	O
+Q	O
+tau	O
+ratio	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+MIP	O
+,	O
+MMIF	O
+,	O
+FIC	O
+,	O
+Wimax	O
+,	O
+P0	O
+.	O
+1	O
+and	O
+minute	O
+ventilation	O
+(	O
+Vr	O
+)	O
+were	O
+significantly	O
+increased	O
+after	O
+administration	O
+of	O
+methylphenidatum	O
+and	O
+aminophylline	O
+.	O
+
+It	O
+has	O
+also	O
+been	O
+shown	O
+that	O
+a	O
+variety	O
+of	O
+extracellular	O
+factors	O
+stimulate	O
+a	O
+pair	O
+of	O
+MAPK	O
+p44	B-GENE
+and	O
+MAPK	O
+p42	B-GENE
+of	O
+MAPK	B-GENE
+family	I-GENE
+members	I-GENE
+.	O
+
+Covalent	O
+modification	O
+of	O
+the	O
+transactivator	O
+protein	O
+IE2	B-GENE
+-	O
+p86	B-GENE
+of	O
+human	O
+cytomegalovirus	O
+by	O
+conjugation	O
+to	O
+the	O
+ubiquitin	B-GENE
+-	I-GENE
+homologous	I-GENE
+proteins	I-GENE
+SUMO	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+hSMT3b	B-GENE
+.	O
+
+73	O
+:	O
+658	O
+-	O
+666	O
+,	O
+1999	O
+)	O
+.	O
+
+The	O
+interaction	O
+between	O
+U	O
+(	O
+L	O
+)	O
+3	O
+.	O
+
+Protamine	B-GENE
+and	O
+heparin	O
+doses	O
+,	O
+their	O
+sum	O
+(	O
+Sigma	O
+-	O
+dose	O
+)	O
+and	O
+differential	O
+(	O
+Delta	O
+-	O
+dose	O
+)	O
+doses	O
+,	O
+and	O
+activated	O
+clotting	O
+times	O
+were	O
+tabulated	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+a	O
+common	O
+mechanism	O
+has	O
+been	O
+identified	O
+to	O
+coordinate	O
+the	O
+growth	O
+-	O
+and	O
+FC	O
+-	O
+dependent	O
+expression	O
+of	O
+caveolin	B-GENE
+.	O
+
+Comparison	O
+of	O
+the	O
+plant	O
+nuclear	O
+tRNA	O
+3	O
+'	O
+processing	O
+enzyme	O
+with	O
+the	O
+plant	O
+mitochondrial	O
+one	O
+suggests	O
+that	O
+both	O
+activities	O
+are	O
+different	O
+enzymes	O
+.	O
+
+NKX2	B-GENE
+.	I-GENE
+1	I-GENE
+is	O
+a	O
+member	O
+of	O
+the	O
+NK2	B-GENE
+family	I-GENE
+of	O
+homeodomain	B-GENE
+-	I-GENE
+containing	I-GENE
+transcription	I-GENE
+factors	I-GENE
+whose	O
+targeted	O
+disruption	O
+in	O
+mouse	O
+results	O
+in	O
+the	O
+absence	O
+of	O
+thyroid	O
+tissue	O
+and	O
+a	O
+severely	O
+abnormal	O
+lung	O
+phenotype	O
+.	O
+
+National	O
+abortion	O
+laws	O
+usually	O
+do	O
+not	O
+allow	O
+abortion	O
+when	O
+a	O
+foetus	O
+is	O
+independently	O
+viable	O
+,	O
+i	O
+.	O
+e	O
+.	O
+from	O
+a	O
+gestational	O
+age	O
+of	O
+about	O
+24	O
+weeks	O
+.	O
+
+Deglutition	O
+is	O
+considered	O
+to	O
+be	O
+immature	O
+in	O
+infants	O
+and	O
+to	O
+mature	O
+postnatally	O
+.	O
+
+This	O
+repression	O
+does	O
+not	O
+require	O
+the	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+transactivation	O
+or	O
+PEST	O
+domains	O
+and	O
+cannot	O
+be	O
+reversed	O
+by	O
+p300	B-GENE
+expression	O
+.	O
+
+First	O
+,	O
+human	O
+erythroid	O
+K562	O
+cells	O
+stably	O
+integrated	O
+with	O
+various	O
+HS	B-GENE
+-	I-GENE
+40	I-GENE
+mutants	I-GENE
+cis	O
+linked	O
+to	O
+a	O
+human	B-GENE
+alpha	I-GENE
+-	I-GENE
+globin	I-GENE
+promoter	I-GENE
+-	O
+growth	B-GENE
+hormone	I-GENE
+hybrid	O
+gene	O
+were	O
+analyzed	O
+by	O
+genomic	O
+footprinting	O
+and	O
+expression	O
+analysis	O
+.	O
+
+Interestingly	O
+,	O
+addition	O
+of	O
+purified	O
+CBP	B-GENE
+to	O
+the	O
+nuclear	O
+extracts	O
+of	O
+T47D	O
+cells	O
+markedly	O
+stimulated	O
+progesterone	O
+-	O
+and	O
+PR	B-GENE
+-	O
+dependent	O
+transcription	O
+from	O
+a	O
+nucleosome	O
+-	O
+free	O
+,	O
+progesterone	O
+response	O
+element	O
+(	O
+PRE	O
+)	O
+-	O
+linked	O
+reporter	O
+DNA	O
+template	O
+.	O
+
+Its	O
+cognate	O
+binding	O
+protein	O
+,	O
+REST	B-GENE
+/	O
+NRSF	B-GENE
+,	O
+is	O
+an	O
+essential	O
+transcription	O
+factor	O
+;	O
+its	O
+null	O
+mutations	O
+result	O
+in	O
+embryonic	O
+lethality	O
+,	O
+and	O
+its	O
+dominant	O
+negative	O
+mutants	O
+produce	O
+aberrant	O
+expression	O
+of	O
+neuron	O
+-	O
+specific	O
+genes	O
+.	O
+
+Removal	O
+of	O
+all	O
+core	B-GENE
+histone	I-GENE
+tail	O
+domains	O
+by	O
+limited	O
+trypsin	B-GENE
+proteolysis	O
+or	O
+acetylation	O
+of	O
+the	O
+core	B-GENE
+histone	I-GENE
+tails	O
+significantly	O
+relieves	O
+this	O
+inhibition	O
+and	O
+allows	O
+TFIIIA	B-GENE
+to	O
+exhibit	O
+high	O
+-	O
+affinity	O
+binding	O
+to	O
+nucleosomal	O
+DNA	O
+.	O
+
+OUTCOME	O
+:	O
+Acetylcholine	B-GENE
+receptor	I-GENE
+antibodies	I-GENE
+and	O
+single	O
+-	O
+fibre	O
+electromyogram	O
+were	O
+useful	O
+in	O
+the	O
+diagnosis	O
+of	O
+myasthenia	O
+gravis	O
+.	O
+
+Characterization	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B-GENE
+multidrug	I-GENE
+resistance	I-GENE
+protein	I-GENE
+2	I-GENE
+(	O
+MRP2	B-GENE
+)	O
+gene	O
+and	O
+its	O
+regulation	O
+in	O
+comparison	O
+withthe	O
+multidrug	B-GENE
+resistance	I-GENE
+protein	I-GENE
+3	I-GENE
+(	O
+MRP3	B-GENE
+)	O
+gene	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+the	O
+M	O
+.	O
+jannaschii	O
+as	O
+well	O
+as	O
+related	O
+archaeal	B-GENE
+20S	I-GENE
+proteasomes	I-GENE
+require	O
+a	O
+nucleotidase	O
+complex	O
+such	O
+as	O
+PAN	B-GENE
+to	O
+mediate	O
+the	O
+energy	O
+-	O
+dependent	O
+hydrolysis	O
+of	O
+folded	O
+-	O
+substrate	O
+proteins	O
+and	O
+that	O
+the	O
+N	O
+-	O
+terminal	O
+73	O
+amino	O
+acid	O
+residues	O
+of	O
+PAN	B-GENE
+are	O
+not	O
+absolutely	O
+required	O
+for	O
+this	O
+reaction	O
+.	O
+
+The	O
+transcription	O
+factor	O
+E2F	B-GENE
+plays	O
+an	O
+important	O
+role	O
+in	O
+G	O
+(	O
+1	O
+)	O
+to	O
+S	O
+phase	O
+transition	O
+in	O
+the	O
+higher	O
+eukaryotic	O
+cell	O
+cycle	O
+.	O
+
+In	O
+two	O
+-	O
+field	O
+nodal	O
+dissection	O
+,	O
+two	O
+components	O
+are	O
+included	O
+with	O
+(	O
+modern	O
+two	O
+-	O
+field	O
+)	O
+or	O
+without	O
+(	O
+traditional	O
+two	O
+-	O
+field	O
+)	O
+nodal	O
+dissection	O
+around	O
+both	O
+recurrent	O
+laryngeal	O
+nerve	O
+chains	O
+in	O
+the	O
+upper	O
+mediastinum	O
+.	O
+
+Of	O
+the	O
+153	O
+patients	O
+studied	O
+,	O
+CK	B-GENE
+-	I-GENE
+MB	I-GENE
+results	O
+were	O
+positive	O
+in	O
+91	O
+(	O
+59	O
+%	O
+)	O
+patients	O
+;	O
+ECG	O
+revealed	O
+AMI	O
+in	O
+72	O
+(	O
+47	O
+%	O
+)	O
+patients	O
+.	O
+
+The	O
+effect	O
+of	O
+MIB	O
+on	O
+the	O
+dose	O
+-	O
+response	O
+curve	O
+of	O
+externally	O
+applied	O
+noradrenaline	O
+was	O
+also	O
+studied	O
+.	O
+
+The	O
+regional	O
+blockade	O
+of	O
+H1R	B-GENE
+was	O
+observed	O
+mainly	O
+in	O
+the	O
+frontal	O
+,	O
+temporal	O
+and	O
+anterior	O
+cingulate	O
+cortices	O
+,	O
+and	O
+the	O
+intravenous	O
+administration	O
+of	O
+d	O
+-	O
+chlorpheniramine	O
+as	O
+a	O
+therapeutic	O
+dose	O
+(	O
+2	O
+mg	O
+)	O
+blocked	O
+over	O
+60	O
+%	O
+of	O
+H1R	B-GENE
+in	O
+the	O
+frontal	O
+cortices	O
+.	O
+
+Linearized	O
+overall	O
+infection	O
+rates	O
+(	O
+events	O
+/	O
+100	O
+patient	O
+-	O
+days	O
+)	O
+were	O
+2	O
+.	O
+05	O
++	O
+/	O
+-	O
+0	O
+.	O
+33	O
+(	O
+heart	O
+-	O
+lung	O
+)	O
+and	O
+2	O
+.	O
+34	O
++	O
+/	O
+-	O
+0	O
+.	O
+34	O
+(	O
+double	O
+-	O
+lung	O
+;	O
+P	O
+=	O
+NS	O
+)	O
+at	O
+3	O
+months	O
+.	O
+
+Static	O
+and	O
+dynamic	O
+compliance	O
+was	O
+measured	O
+after	O
+induction	O
+of	O
+anesthesia	O
+,	O
+before	O
+and	O
+immediately	O
+after	O
+filtration	O
+in	O
+the	O
+operating	O
+theater	O
+,	O
+1	O
+hour	O
+after	O
+return	O
+to	O
+the	O
+pediatric	O
+intensive	O
+care	O
+unit	O
+,	O
+and	O
+24	O
+hours	O
+after	O
+the	O
+operation	O
+.	O
+
+Antipyretic	O
+therapy	O
+:	O
+physiologic	O
+rationale	O
+,	O
+diagnostic	O
+implications	O
+,	O
+and	O
+clinical	O
+consequences	O
+.	O
+
+There	O
+is	O
+no	O
+correlation	O
+between	O
+C2	O
+-	O
+C3	O
+disk	O
+morphology	O
+and	O
+the	O
+diskographically	O
+provoked	O
+response	O
+.	O
+
+KFC	B-GENE
+,	O
+a	O
+Ste20	B-GENE
+-	I-GENE
+like	I-GENE
+kinase	I-GENE
+with	O
+mitogenic	O
+potential	O
+and	O
+capability	O
+to	O
+activate	O
+the	O
+SAPK	B-GENE
+/	O
+JNK	B-GENE
+pathway	O
+.	O
+
+We	O
+have	O
+mapped	O
+the	O
+human	B-GENE
+STAG3	I-GENE
+gene	I-GENE
+to	O
+the	O
+7q22	O
+region	O
+of	O
+chromosome	O
+7	O
+;	O
+six	O
+human	B-GENE
+STAG3	I-GENE
+-	I-GENE
+related	I-GENE
+genes	I-GENE
+have	O
+also	O
+been	O
+mapped	O
+:	O
+two	O
+at	O
+7q22	O
+near	O
+the	O
+functional	O
+gene	O
+,	O
+one	O
+at	O
+7q11	O
+.	O
+22	O
+,	O
+and	O
+three	O
+at	O
+7q11	O
+.	O
+23	O
+,	O
+two	O
+of	O
+them	O
+flanking	O
+the	O
+breakpoints	O
+commonly	O
+associated	O
+with	O
+the	O
+Williams	B-GENE
+-	I-GENE
+Beuren	I-GENE
+syndrome	I-GENE
+(	I-GENE
+WBS	I-GENE
+)	I-GENE
+deletion	I-GENE
+.	O
+
+Reaction	O
+time	O
+(	O
+RT	O
+)	O
+and	O
+P300	O
+were	O
+collected	O
+simultaneously	O
+.	O
+
+In	O
+experiment	O
+2	O
+the	O
+rats	O
+had	O
+free	O
+access	O
+to	O
+two	O
+bottles	O
+,	O
+one	O
+of	O
+which	O
+contained	O
+tap	O
+water	O
+,	O
+and	O
+the	O
+other	O
+contained	O
+either	O
+an	O
+ethanol	O
+(	O
+6	O
+%	O
+)	O
+or	O
+a	O
+sucrose	O
+(	O
+5	O
+%	O
+)	O
+solution	O
+.	O
+
+Furthermore	O
+,	O
+Zelen	O
+'	O
+s	O
+method	O
+is	O
+used	O
+to	O
+balance	O
+the	O
+number	O
+of	O
+patients	O
+allocated	O
+to	O
+the	O
+two	O
+groups	O
+within	O
+each	O
+institution	O
+(	O
+M	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+this	O
+group	O
+of	O
+patients	O
+,	O
+male	O
+gender	O
+(	O
+P	O
+=	O
+0	O
+.	O
+
+Selective	O
+visual	O
+attention	O
+involves	O
+dynamic	O
+interplay	O
+between	O
+attentional	O
+control	O
+systems	O
+and	O
+sensory	O
+brain	O
+structures	O
+.	O
+
+The	O
+patient	O
+had	O
+developed	O
+left	O
+-	O
+sided	O
+low	O
+-	O
+frequency	O
+tremor	O
+and	O
+hemidystonia	O
+after	O
+a	O
+severe	O
+head	O
+trauma	O
+sustained	O
+at	O
+15	O
+years	O
+of	O
+age	O
+.	O
+
+However	O
+,	O
+the	O
+a1	O
+isoform	O
+is	O
+expressed	O
+most	O
+heavily	O
+in	O
+brain	O
+and	O
+heart	O
+,	O
+a2	O
+in	O
+liver	O
+and	O
+kidney	O
+,	O
+and	O
+a3	O
+in	O
+liver	O
+,	O
+lung	O
+,	O
+heart	O
+,	O
+brain	O
+,	O
+spleen	O
+,	O
+and	O
+kidney	O
+.	O
+
+During	O
+the	O
+cloning	O
+by	O
+reverse	B-GENE
+transcriptase	I-GENE
+-	O
+polymerase	O
+chain	O
+reaction	O
+of	O
+the	O
+human	B-GENE
+HIF	I-GENE
+-	I-GENE
+1alpha	I-GENE
+subunit	I-GENE
+,	O
+we	O
+isolated	O
+two	O
+cDNA	O
+clones	O
+which	O
+corresponded	O
+to	O
+alternative	O
+splicing	O
+of	O
+the	O
+HIF	B-GENE
+-	I-GENE
+1alpha	I-GENE
+gene	I-GENE
+.	O
+
+To	O
+assess	O
+the	O
+relationship	O
+between	O
+G	B-GENE
+(	I-GENE
+q	I-GENE
+)	I-GENE
+/	O
+G	B-GENE
+(	I-GENE
+11	I-GENE
+)	I-GENE
+function	O
+with	O
+the	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+dependent	O
+pathway	O
+,	O
+expression	O
+of	O
+a	O
+dominant	O
+-	O
+interfering	O
+p85	B-GENE
+regulatory	I-GENE
+subunit	I-GENE
+,	O
+as	O
+well	O
+as	O
+wortmannin	O
+treatment	O
+inhibited	O
+insulin	B-GENE
+-	O
+stimulated	O
+but	O
+not	O
+G	B-GENE
+(	I-GENE
+q	I-GENE
+)	I-GENE
+/	I-GENE
+Q209L	I-GENE
+-	O
+stimulated	O
+GLUT4	B-GENE
+-	O
+EGFP	B-GENE
+translocation	O
+.	O
+
+In	O
+endemic	O
+BL	O
+,	O
+the	O
+RB2	B-GENE
+/	O
+p130	B-GENE
+gene	O
+is	O
+mutated	O
+in	O
+most	O
+of	O
+the	O
+cases	O
+,	O
+and	O
+the	O
+protein	O
+is	O
+restricted	O
+to	O
+the	O
+cytoplasm	O
+.	O
+
+Together	O
+,	O
+these	O
+data	O
+identify	O
+ERK2	B-GENE
+as	O
+a	O
+specific	O
+and	O
+direct	O
+target	O
+of	O
+HePTP	B-GENE
+and	O
+are	O
+consistent	O
+with	O
+a	O
+model	O
+in	O
+which	O
+HePTP	B-GENE
+negatively	O
+regulates	O
+ERK2	B-GENE
+activity	O
+as	O
+part	O
+of	O
+a	O
+feedback	O
+mechanism	O
+.	O
+
+Cross	O
+-	O
+reaction	O
+between	O
+a	O
+monoclonal	O
+antibody	O
+and	O
+two	O
+alpha	B-GENE
+beta	I-GENE
+T	I-GENE
+cell	I-GENE
+receptors	I-GENE
+.	O
+
+Strontium	O
+nitrate	O
+mixed	O
+with	O
+glycolic	O
+acid	O
+,	O
+in	O
+comparison	O
+with	O
+glycolic	O
+acid	O
+alone	O
+,	O
+markedly	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+shortened	O
+the	O
+duration	O
+of	O
+the	O
+irritation	O
+sensation	O
+from	O
+24	O
+.	O
+4	O
++	O
+/	O
+-	O
+4	O
+.	O
+1	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SEM	O
+)	O
+min	O
+to	O
+8	O
+.	O
+9	O
++	O
+/	O
+-	O
+3	O
+.	O
+7	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SEM	O
+)	O
+min	O
+,	O
+and	O
+significantly	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+reduced	O
+the	O
+mean	O
+magnitude	O
+of	O
+the	O
+irritation	O
+sensation	O
+at	O
+all	O
+time	O
+points	O
+(	O
+overall	O
+)	O
+.	O
+
+The	O
+pCMBS	O
+-	O
+reactive	O
+sulfhydryl	O
+groups	O
+were	O
+located	O
+exclusively	O
+in	O
+the	O
+exofacial	O
+half	O
+of	O
+the	O
+plasma	O
+membrane	O
+and	O
+,	O
+when	O
+presented	O
+in	O
+a	O
+helical	O
+model	O
+,	O
+lie	O
+along	O
+one	O
+side	O
+of	O
+the	O
+helices	O
+.	O
+
+Analysis	O
+of	O
+1	O
+Mb	O
+of	O
+published	O
+sequence	O
+from	O
+the	O
+region	O
+of	O
+conserved	O
+synteny	O
+on	O
+human	O
+chromosome	O
+5q31	O
+-	O
+q33	O
+identified	O
+45	O
+gene	O
+candidates	O
+,	O
+including	O
+35	O
+expressed	O
+genes	O
+in	O
+the	O
+human	B-GENE
+IL	I-GENE
+-	I-GENE
+4	I-GENE
+cytokine	I-GENE
+gene	I-GENE
+cluster	I-GENE
+.	O
+
+Human	B-GENE
+AP	I-GENE
+-	I-GENE
+2rep	I-GENE
+repressed	O
+both	O
+reporter	O
+expression	O
+from	O
+a	O
+transiently	O
+transfected	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+promoter	I-GENE
+and	O
+the	O
+endogenous	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+gene	I-GENE
+and	O
+inversely	O
+was	O
+negatively	O
+regulated	O
+by	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+.	O
+
+In	O
+order	O
+to	O
+gain	O
+deeper	O
+insight	O
+into	O
+the	O
+role	O
+of	O
+the	O
+amino	O
+-	O
+terminal	O
+domain	O
+of	O
+the	O
+p24	B-GENE
+(	O
+CA	B-GENE
+)	O
+protein	O
+during	O
+viral	O
+replication	O
+,	O
+eight	O
+highly	O
+conserved	O
+proline	O
+residues	O
+known	O
+to	O
+promote	O
+turns	O
+and	O
+to	O
+terminate	O
+alpha	O
+-	O
+helices	O
+within	O
+the	O
+p24	B-GENE
+tertiary	O
+structure	O
+were	O
+replaced	O
+by	O
+a	O
+leucine	O
+residue	O
+(	O
+P	O
+-	O
+position	O
+-	O
+L	O
+)	O
+.	O
+
+Clb	B-GENE
+/	O
+Cdc28	B-GENE
+kinases	O
+promote	O
+nuclear	O
+export	O
+of	O
+the	O
+replication	B-GENE
+initiator	I-GENE
+proteins	I-GENE
+Mcm2	I-GENE
+-	I-GENE
+7	I-GENE
+.	O
+
+Cooperative	O
+roles	O
+of	O
+Bozozok	B-GENE
+/	O
+Dharma	B-GENE
+and	O
+Nodal	B-GENE
+-	I-GENE
+related	I-GENE
+proteins	I-GENE
+in	O
+the	O
+formation	O
+of	O
+the	O
+dorsal	O
+organizer	O
+in	O
+zebrafish	O
+.	O
+
+Thiopentone	O
+sodium	O
+administered	O
+at	O
+30	O
+and	O
+10	O
+min	O
+before	O
+or	O
+5	O
+,	O
+10	O
+and	O
+15	O
+min	O
+after	O
+exposure	O
+to	O
+NOC	O
+-	O
+5	O
+,	O
+but	O
+not	O
+thereafter	O
+,	O
+significantly	O
+attenuated	O
+NO	O
+-	O
+induced	O
+neurotoxicity	O
+compared	O
+with	O
+controls	O
+.	O
+
+We	O
+also	O
+show	O
+that	O
+zygotically	O
+activated	O
+Xretpos	O
+transcripts	O
+are	O
+restricted	O
+to	O
+ventro	O
+-	O
+posterior	O
+specific	O
+regions	O
+and	O
+induced	O
+by	O
+UV	O
+-	O
+irradiation	O
+and	O
+BMP	B-GENE
+-	I-GENE
+4	I-GENE
+overexpression	O
+in	O
+cycloheximide	O
+-	O
+dependent	O
+way	O
+.	O
+genesis	O
+26	O
+:	O
+198	O
+-	O
+207	O
+,	O
+2000	O
+.	O
+
+In	O
+all	O
+other	O
+cases	O
+,	O
+vestibular	O
+neurectomy	O
+or	O
+chemical	O
+vestibular	O
+labyrinthectomy	O
+,	O
+by	O
+means	O
+of	O
+intratympanic	O
+low	O
+concentration	O
+gentamicin	O
+(	O
+20	O
+mg	O
+/	O
+mL	O
+)	O
+,	O
+are	O
+indicated	O
+.	O
+
+However	O
+,	O
+when	O
+,	O
+where	O
+and	O
+how	O
+the	O
+DSPP	B-GENE
+is	O
+cleaved	O
+into	O
+DSP	B-GENE
+and	O
+DPP	B-GENE
+is	O
+not	O
+clear	O
+.	O
+
+It	O
+has	O
+a	O
+grave	O
+prognosis	O
+with	O
+>	O
+70	O
+%	O
+mortality	O
+in	O
+3	O
+months	O
+,	O
+despite	O
+mechanical	O
+ventilation	O
+.	O
+
+We	O
+found	O
+that	O
+TCR	B-GENE
+signaling	O
+induces	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+binding	O
+to	O
+this	O
+site	O
+and	O
+regulates	O
+the	O
+fasl	B-GENE
+promoter	I-GENE
+function	O
+in	O
+a	O
+fashion	O
+dependent	O
+on	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+binding	O
+.	O
+
+Thus	O
+,	O
+patients	O
+with	O
+metastatic	O
+melanoma	O
+are	O
+not	O
+tolerant	O
+to	O
+gp100	B-GENE
+Ag	I-GENE
+based	O
+on	O
+the	O
+detection	O
+of	O
+CD8	B-GENE
++	I-GENE
+T	O
+cells	O
+specific	O
+for	O
+multiple	O
+HLA	B-GENE
+-	I-GENE
+A	I-GENE
+*	I-GENE
+0201	I-GENE
+-	O
+restricted	O
+,	O
+gp100	B-GENE
+-	O
+derived	O
+epitopes	O
+.	O
+
+Following	O
+the	O
+observation	O
+that	O
+non	O
+-	O
+organ	O
+-	O
+specific	O
+antibodies	O
+are	O
+related	O
+with	O
+pregnancy	O
+loss	O
+and	O
+preeclampsia	O
+,	O
+the	O
+role	O
+of	O
+organ	O
+-	O
+specific	O
+antibodies	O
+is	O
+currently	O
+being	O
+extensively	O
+investigated	O
+.	O
+
+The	O
+Mif1	B-GENE
+5	I-GENE
+'	I-GENE
+flanking	I-GENE
+region	I-GENE
+contains	O
+a	O
+functional	O
+ER	O
+stress	O
+-	O
+responsive	O
+element	O
+which	O
+is	O
+sufficient	O
+for	O
+induction	O
+by	O
+tunicamycin	O
+.	O
+
+Rigid	O
+point	O
+feature	O
+registration	O
+using	O
+mutual	O
+information	O
+.	O
+
+Methysergide	O
+is	O
+a	O
+serotonin	O
+antagonist	O
+and	O
+has	O
+been	O
+demonstrated	O
+to	O
+reduce	O
+wound	O
+blood	O
+flow	O
+and	O
+edema	O
+formation	O
+.	O
+
+Serum	O
+leptin	B-GENE
+concentrations	O
+in	O
+women	O
+during	O
+gonadotropin	B-GENE
+stimulation	O
+cycles	O
+.	O
+
+Valuing	O
+families	O
+:	O
+social	O
+work	O
+practice	O
+with	O
+families	O
+from	O
+a	O
+strengths	O
+perspective	O
+.	O
+
+PURPOSE	O
+:	O
+A	O
+two	O
+-	O
+generation	O
+consanguineous	O
+Pakistani	O
+family	O
+with	O
+autosomal	O
+recessive	O
+Leber	O
+congenital	O
+amaurosis	O
+(	O
+LCA	O
+,	O
+MIM	O
+204	O
+,	O
+000	O
+)	O
+and	O
+keratoconus	O
+was	O
+identified	O
+.	O
+
+Ste18p	B-GENE
+was	O
+targeted	O
+to	O
+the	O
+plasma	O
+membrane	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+prenylation	O
+or	O
+thioacylation	O
+.	O
+
+Here	O
+,	O
+we	O
+show	O
+that	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+degraded	O
+via	O
+the	O
+ubiquitin	B-GENE
+-	O
+proteasome	O
+pathway	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+IIIa	O
+pre	O
+-	O
+mRNA	O
+splicing	O
+is	O
+activated	O
+more	O
+than	O
+200	O
+-	O
+fold	O
+in	O
+nuclear	O
+extracts	O
+prepared	O
+from	O
+late	O
+adenovirus	O
+-	O
+infected	O
+cells	O
+(	O
+Ad	O
+-	O
+NE	O
+)	O
+compared	O
+to	O
+uninfected	O
+HeLa	O
+cell	O
+nuclear	O
+extracts	O
+(	O
+HeLa	O
+-	O
+NE	O
+)	O
+.	O
+
+Inactivation	O
+of	O
+Ulp2	B-GENE
+also	O
+suppresses	O
+several	O
+ulp1	B-GENE
+(	I-GENE
+ts	I-GENE
+)	I-GENE
+defects	O
+,	O
+and	O
+the	O
+double	O
+mutant	O
+accumulates	O
+far	O
+fewer	O
+Smt3	B-GENE
+-	I-GENE
+protein	I-GENE
+conjugates	O
+than	O
+either	O
+single	O
+mutant	O
+.	O
+
+Cyclin	B-GENE
+A	I-GENE
+expression	O
+is	O
+repressed	O
+in	O
+quiescent	O
+cells	O
+by	O
+E2F	B-GENE
+acting	O
+in	O
+conjunction	O
+with	O
+its	O
+pocket	O
+protein	O
+partners	O
+Rb	B-GENE
+,	O
+p107	B-GENE
+,	O
+and	O
+p130	B-GENE
+;	O
+however	O
+,	O
+v	B-GENE
+-	I-GENE
+Jun	I-GENE
+overrides	O
+this	O
+control	O
+,	O
+causing	O
+phosphorylated	O
+Rb	B-GENE
+and	O
+proliferation	O
+-	O
+specific	O
+E2F	B-GENE
+-	O
+p107	B-GENE
+complexes	O
+to	O
+persist	O
+after	O
+mitogen	O
+withdrawal	O
+.	O
+
+D	B-GENE
+-	I-GENE
+cyclin	I-GENE
+-	O
+cdk	B-GENE
+activity	O
+is	O
+required	O
+for	O
+Rb	B-GENE
+phosphorylation	O
+in	O
+v	B-GENE
+-	I-GENE
+Jun	I-GENE
+-	O
+transformed	O
+cells	O
+,	O
+since	O
+ectopic	O
+expression	O
+of	O
+the	O
+cdk4	B-GENE
+-	O
+and	O
+cdk6	B-GENE
+-	O
+specific	O
+inhibitor	O
+p16	B-GENE
+(	O
+INK4A	B-GENE
+)	O
+inhibits	O
+both	O
+DNA	O
+synthesis	O
+and	O
+cell	O
+proliferation	O
+.	O
+
+CONCLUSION	O
+:	O
+A	O
+valve	O
+-	O
+like	O
+mechanism	O
+formed	O
+by	O
+the	O
+capsulorhexis	O
+rim	O
+partially	O
+adhered	O
+to	O
+the	O
+IOL	O
+optic	O
+can	O
+occur	O
+postoperatively	O
+.	O
+
+The	O
+protein	O
+first	O
+identified	O
+by	O
+the	O
+monoclonal	B-GENE
+antibody	I-GENE
+Q18	I-GENE
+is	O
+encoded	O
+by	O
+a	O
+gene	O
+located	O
+in	O
+57A	O
+on	O
+polytene	O
+chromosomes	O
+and	O
+has	O
+been	O
+consequently	O
+named	O
+Hrb57A	B-GENE
+.	O
+
+3	O
+'	O
+RNA	O
+boundary	O
+experiments	O
+indicate	O
+that	O
+the	O
+5	O
+'	O
+structure	O
+reduces	O
+the	O
+number	O
+of	O
+(	O
+G	O
+/	O
+U	O
+)	O
+AG	O
+repeats	O
+required	O
+for	O
+stable	O
+TRAP	B-GENE
+-	O
+trp	B-GENE
+leader	O
+RNA	O
+association	O
+.	O
+
+Gene	O
+silencing	O
+associated	O
+with	O
+repeated	O
+DNA	O
+sequences	O
+has	O
+been	O
+reported	O
+for	O
+many	O
+eukaryotes	O
+,	O
+including	O
+plants	O
+.	O
+
+Animals	O
+received	O
+a	O
+dose	O
+of	O
+dexamethasone	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+prior	O
+to	O
+the	O
+protein	O
+-	O
+free	O
+surfactant	O
+preparation	O
+Exosurf	O
+(	O
+pure	O
+phospholipids	O
+containing	O
+surfactant	O
+,	O
+Wellcome	O
+GmbH	O
+,	O
+Burgwedel	O
+,	O
+Germany	O
+)	O
+and	O
+a	O
+rSP	O
+-	O
+C	O
+based	O
+surfactant	O
+,	O
+respectively	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+response	O
+rates	O
+and	O
+toxicity	O
+of	O
+two	O
+regimens	O
+containing	O
+granulocyte	B-GENE
+-	I-GENE
+macrophage	I-GENE
+-	I-GENE
+colony	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+in	O
+combination	O
+with	O
+interleukin	B-GENE
+-	I-GENE
+2	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+in	O
+the	O
+treatment	O
+of	O
+patients	O
+with	O
+metastatic	O
+renal	O
+cell	O
+carcinoma	O
+.	O
+
+We	O
+show	O
+,	O
+by	O
+injection	O
+of	O
+synthetic	O
+mRNAs	O
+,	O
+that	O
+the	O
+cis	O
+-	O
+acting	O
+sequences	O
+responsible	O
+for	O
+repression	O
+of	O
+cyclin	B-GENE
+B1	I-GENE
+mRNA	I-GENE
+reside	O
+within	O
+its	O
+3	O
+'	O
+UTR	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+expansion	O
+of	O
+the	O
+dodecamer	O
+repeat	O
+located	O
+in	O
+the	O
+proximal	O
+promoter	O
+of	O
+CSTB	B-GENE
+severely	O
+disrupts	O
+the	O
+function	O
+of	O
+the	O
+promoter	O
+and	O
+thereby	O
+reduces	O
+transcription	O
+of	O
+CSTB	B-GENE
+.	O
+
+Thus	O
+,	O
+while	O
+the	O
+genomic	O
+organization	O
+of	O
+mHuA	B-GENE
+is	O
+similar	O
+to	O
+the	O
+neural	O
+-	O
+restricted	O
+members	O
+of	O
+the	O
+Elav	B-GENE
+family	I-GENE
+,	O
+the	O
+promoter	O
+element	O
+differs	O
+substantially	O
+both	O
+by	O
+sequence	O
+analysis	O
+and	O
+transcriptional	O
+activity	O
+in	O
+non	O
+-	O
+neural	O
+cell	O
+types	O
+.	O
+
+Analysis	O
+of	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+mouse	B-GENE
+Elavl1	I-GENE
+(	O
+mHuA	B-GENE
+)	O
+gene	O
+reveals	O
+a	O
+transcriptional	O
+regulatory	O
+element	O
+and	O
+evidence	O
+for	O
+conserved	O
+genomic	O
+organization	O
+.	O
+mHuA	B-GENE
+(	O
+Elavl1	B-GENE
+)	O
+belongs	O
+to	O
+a	O
+highly	O
+conserved	O
+family	O
+of	O
+genes	O
+encoding	O
+RNA	O
+-	O
+binding	O
+proteins	O
+and	O
+has	O
+been	O
+linked	O
+to	O
+cell	O
+growth	O
+and	O
+proliferation	O
+through	O
+its	O
+regulation	O
+of	O
+mRNA	O
+stability	O
+.	O
+
+Fgd3	B-GENE
+and	O
+FGD1	B-GENE
+share	O
+a	O
+high	O
+degree	O
+of	O
+sequence	O
+identity	O
+that	O
+spans	O
+>	O
+560	O
+contiguous	O
+amino	O
+acid	O
+residues	O
+.	O
+
+Molecular	O
+cloning	O
+of	O
+mouse	B-GENE
+thioredoxin	I-GENE
+reductases	I-GENE
+.	O
+
+The	O
+HPLC	O
+method	O
+involves	O
+an	O
+octadecylsilane	O
+column	O
+at	O
+55	O
+degrees	O
+C	O
+,	O
+a	O
+mixture	O
+of	O
+water	O
+-	O
+acetonitrile	O
+-	O
+orthophosphoric	O
+acid	O
+(	O
+779	O
+:	O
+220	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+as	O
+mobile	O
+phase	O
+and	O
+detection	O
+at	O
+226	O
+nm	O
+.	O
+
+CYC2	B-GENE
+encodes	O
+a	O
+24	O
+-	O
+kDa	O
+protein	O
+that	O
+has	O
+sequence	O
+identity	O
+to	O
+the	O
+Neurospora	B-GENE
+crassa	I-GENE
+PREG1	I-GENE
+and	O
+the	O
+S	B-GENE
+.	I-GENE
+cerevisiae	I-GENE
+PHO80	I-GENE
+cyclin	I-GENE
+.	O
+
+To	O
+determine	O
+if	O
+CYC2	B-GENE
+is	O
+found	O
+in	O
+a	O
+complex	O
+with	O
+previously	O
+identified	O
+trypanosome	B-GENE
+cdc2	I-GENE
+-	I-GENE
+related	I-GENE
+kinases	I-GENE
+(	O
+CRKs	B-GENE
+)	O
+,	O
+the	O
+CYC2	B-GENE
+gene	I-GENE
+was	O
+fused	O
+to	O
+the	O
+TY	B-GENE
+epitope	I-GENE
+tag	O
+,	O
+integrated	O
+into	O
+the	O
+trypanosome	O
+genome	O
+,	O
+and	O
+expressed	O
+under	O
+inducible	O
+control	O
+.	O
+
+These	O
+findings	O
+indicate	O
+the	O
+involvement	O
+of	O
+Sp1	B-GENE
+and	O
+an	O
+Inr	O
+in	O
+non	O
+-	O
+cell	O
+-	O
+specific	O
+regulation	O
+and	O
+a	O
+Kruppel	B-GENE
+-	I-GENE
+like	I-GENE
+transcription	I-GENE
+factor	I-GENE
+and	O
+Sp1	B-GENE
+in	O
+the	O
+cell	O
+-	O
+specific	O
+regulation	O
+of	O
+the	O
+LTC	B-GENE
+(	I-GENE
+4	I-GENE
+)	I-GENE
+S	I-GENE
+gene	I-GENE
+.	O
+
+Here	O
+we	O
+review	O
+progress	O
+to	O
+date	O
+in	O
+this	O
+area	O
+.	O
+
+Additionally	O
+,	O
+the	O
+mouse	O
+promoter	O
+contains	O
+22	O
+copies	O
+of	O
+a	O
+CT	O
+dinucleotide	O
+repeat	O
+sequence	O
+located	O
+approximately	O
+155	O
+bp	O
+5	O
+'	O
+to	O
+exon	O
+1	O
+.	O
+
+The	O
+newly	O
+defined	O
+region	O
+contains	O
+an	O
+intron	O
+that	O
+may	O
+be	O
+alternatively	O
+spliced	O
+and	O
+seven	O
+polyadenylation	O
+signal	O
+sequences	O
+.	O
+
+Depleted	O
+and	O
+enriched	O
+U3O8	O
+standard	O
+reference	O
+materials	O
+were	O
+used	O
+to	O
+calibrate	O
+the	O
+system	O
+.	O
+
+Therefore	O
+,	O
+the	O
+positive	O
+cAMP	O
+control	O
+of	O
+the	O
+hypoxic	O
+SRP1	B-GENE
+and	O
+HEM13	B-GENE
+genes	I-GENE
+was	O
+uncoupled	O
+from	O
+the	O
+HOG	B-GENE
+pathway	O
+.	O
+
+This	O
+paper	O
+reviews	O
+the	O
+middleware	O
+-	O
+based	O
+approach	O
+adopted	O
+by	O
+CEN	O
+ENV	O
+12967	O
+-	O
+1	O
+and	O
+the	O
+specialisation	O
+necessary	O
+for	O
+the	O
+healthcare	O
+record	O
+based	O
+on	O
+CEN	O
+ENV	O
+12265	O
+'	O
+Electronic	O
+Healthcare	O
+Record	O
+Architecture	O
+'	O
+.	O
+
+Sequence	O
+analyses	O
+of	O
+sos2	B-GENE
+mutant	I-GENE
+alleles	I-GENE
+reveal	O
+that	O
+both	O
+the	O
+N	O
+-	O
+terminal	O
+catalytic	O
+domain	O
+and	O
+the	O
+C	O
+-	O
+terminal	O
+regulatory	O
+domain	O
+of	O
+SOS2	B-GENE
+are	O
+functionally	O
+essential	O
+.	O
+
+A	O
+mutation	O
+which	O
+abrogates	O
+the	O
+binding	O
+of	O
+these	O
+factors	O
+reduces	O
+Wp	B-GENE
+reporter	I-GENE
+activity	O
+specifically	O
+in	O
+B	O
+cell	O
+lines	O
+,	O
+whereas	O
+a	O
+mutation	O
+which	O
+converts	O
+the	O
+site	O
+to	O
+a	O
+consensus	O
+CREB	B-GENE
+-	I-GENE
+binding	I-GENE
+sequence	I-GENE
+maintains	O
+wild	O
+-	O
+type	O
+promoter	O
+function	O
+.	O
+
+Therefore	O
+the	O
+binding	O
+sites	O
+for	O
+liver	O
+-	O
+enriched	O
+factors	O
+,	O
+present	O
+in	O
+the	O
+hamster	B-GENE
+CYP7A1	I-GENE
+proximal	I-GENE
+promoter	I-GENE
+in	O
+close	O
+vicinity	O
+and	O
+conserved	O
+between	O
+species	O
+,	O
+constitute	O
+a	O
+regulatory	O
+unit	O
+important	O
+for	O
+basal	O
+hepatic	O
+expression	O
+and	O
+tissue	O
+restriction	O
+of	O
+the	O
+action	O
+of	O
+hormones	O
+such	O
+as	O
+insulin	B-GENE
+.	O
+
+The	O
+kinase	O
+activity	O
+of	O
+PfPK6	B-GENE
+is	O
+sensitive	O
+to	O
+CDK	B-GENE
+inhibitors	O
+such	O
+as	O
+olomoucine	O
+and	O
+roscovitine	O
+.	O
+
+Although	O
+MAP	B-GENE
+(	I-GENE
+mitogen	I-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+)	I-GENE
+kinases	I-GENE
+are	O
+implicated	O
+in	O
+cell	O
+proliferation	O
+and	O
+differentiation	O
+in	O
+many	O
+cell	O
+types	O
+,	O
+the	O
+role	O
+of	O
+MAP	B-GENE
+kinases	I-GENE
+in	O
+cardiac	O
+hypertrophy	O
+remains	O
+unclear	O
+.	O
+
+Transfection	O
+with	O
+a	O
+CSF	B-GENE
+-	I-GENE
+1R	I-GENE
+expression	O
+plasmid	O
+permitted	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+dependent	O
+activation	O
+of	O
+the	O
+signalling	O
+pathway	O
+targeting	O
+an	O
+Ets	B-GENE
+/	O
+AP1	B-GENE
+(	O
+activator	B-GENE
+protein	I-GENE
+1	I-GENE
+)	O
+element	O
+in	O
+the	O
+uPA	B-GENE
+promoter	I-GENE
+that	O
+has	O
+been	O
+shown	O
+previously	O
+to	O
+be	O
+a	O
+target	O
+of	O
+oncogenic	B-GENE
+ras	I-GENE
+and	O
+protein	O
+kinase	O
+C	O
+pathways	O
+.	O
+
+Regulation	O
+of	O
+urokinase	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+gene	I-GENE
+transcription	O
+in	O
+the	O
+RAW264	O
+murine	O
+macrophage	O
+cell	O
+line	O
+by	O
+macrophage	B-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+CSF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+is	O
+dependent	O
+upon	O
+the	O
+level	O
+of	O
+cell	O
+-	O
+surface	O
+receptor	O
+.	O
+
+Molecule	O
+(	O
+s	O
+)	O
+secreted	O
+by	O
+neuronal	O
+cultures	O
+contribute	O
+to	O
+this	O
+induction	O
+of	O
+GLT	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+but	O
+little	O
+is	O
+known	O
+about	O
+the	O
+signaling	O
+pathways	O
+mediating	O
+this	O
+regulation	O
+.	O
+
+Coactivation	O
+of	O
+endogenous	O
+or	O
+exogenous	O
+G	B-GENE
+(	I-GENE
+q	I-GENE
+)	I-GENE
+-	I-GENE
+coupled	I-GENE
+receptors	I-GENE
+with	O
+the	O
+delta	B-GENE
+-	I-GENE
+opioid	I-GENE
+receptor	I-GENE
+produced	O
+strong	O
+stimulations	O
+of	O
+PLCbeta	B-GENE
+and	O
+such	O
+responses	O
+could	O
+be	O
+partially	O
+blocked	O
+by	O
+pertussis	B-GENE
+toxin	I-GENE
+.	O
+
+Patients	O
+enrolled	O
+in	O
+the	O
+Integrilin	O
+to	O
+Minimize	O
+Platelet	O
+Aggregation	O
+and	O
+Coronary	O
+Thrombosis	O
+-	O
+II	O
+(	O
+IMPACT	O
+-	O
+II	O
+)	O
+trial	O
+were	O
+analyzed	O
+.	O
+
+The	O
+Wnt	B-GENE
+signaling	O
+pathway	O
+functions	O
+reiteratively	O
+during	O
+animal	O
+development	O
+to	O
+control	O
+cell	O
+fate	O
+decisions	O
+.	O
+
+This	O
+mutation	O
+no	O
+longer	O
+repressed	O
+the	O
+HPV	O
+-	O
+11	O
+upstream	O
+regulatory	O
+region	O
+-	O
+controlled	O
+reporter	O
+expression	O
+.	O
+
+In	O
+the	O
+icosahaedral	O
+MVMi	O
+capsid	O
+,	O
+this	O
+sequence	O
+forms	O
+the	O
+carboxy	O
+end	O
+of	O
+the	O
+amphipathic	O
+beta	O
+-	O
+strand	O
+I	O
+(	O
+betaI	O
+)	O
+,	O
+and	O
+all	O
+its	O
+basic	O
+residues	O
+are	O
+contiguously	O
+positioned	O
+at	O
+the	O
+face	O
+that	O
+in	O
+the	O
+unassembled	O
+subunit	O
+would	O
+be	O
+exposed	O
+to	O
+solvent	O
+.	O
+
+The	O
+two	O
+contiguous	O
+IGF2	B-GENE
+(	O
+human	B-GENE
+insulin	I-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+II	I-GENE
+)	O
+and	O
+H19	B-GENE
+genes	I-GENE
+are	O
+reciprocally	O
+imprinted	O
+in	O
+both	O
+human	O
+and	O
+mouse	O
+.	O
+
+The	O
+asymmetric	O
+methylation	O
+was	O
+associated	O
+with	O
+tissue	O
+-	O
+specific	O
+disruption	O
+of	O
+H19	B-GENE
+genomic	O
+imprinting	O
+in	O
+fetal	O
+brain	O
+.	O
+
+Early	O
+treatment	O
+mechanics	O
+of	O
+the	O
+Class	O
+II	O
+division	O
+2	O
+malocclusion	O
+.	O
+
+The	O
+consensus	O
+highlights	O
+the	O
+importance	O
+of	O
+residues	O
+other	O
+than	O
+the	O
+eight	O
+motifs	O
+that	O
+are	O
+often	O
+associated	O
+with	O
+DEAD	B-GENE
+-	I-GENE
+box	I-GENE
+RNA	I-GENE
+helicases	I-GENE
+,	O
+as	O
+well	O
+as	O
+de	O
+-	O
+emphasising	O
+the	O
+importance	O
+of	O
+the	O
+"	O
+A	O
+"	O
+residue	O
+within	O
+the	O
+"	O
+DEAD	O
+"	O
+motif	O
+.	O
+
+In	O
+transient	O
+assays	O
+,	O
+using	O
+rice	O
+suspension	O
+-	O
+cultured	O
+cells	O
+transformed	O
+by	O
+particle	O
+bombardment	O
+,	O
+we	O
+showed	O
+previously	O
+that	O
+Oshox1	B-GENE
+can	O
+transcriptionally	O
+repress	O
+the	O
+activity	O
+of	O
+reporter	O
+gene	O
+constructs	O
+with	O
+upstream	O
+HD	B-GENE
+-	I-GENE
+Zip	I-GENE
+binding	O
+sites	O
+.	O
+
+Results	O
+of	O
+two	O
+-	O
+hybrid	O
+assays	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+strongly	O
+suggest	O
+that	O
+all	O
+HD	B-GENE
+-	I-GENE
+Zip	I-GENE
+proteins	I-GENE
+of	O
+families	O
+I	O
+and	O
+II	O
+can	O
+form	O
+homodimers	O
+and	O
+also	O
+heterodimers	O
+with	O
+all	O
+HD	B-GENE
+-	I-GENE
+Zip	I-GENE
+proteins	I-GENE
+of	O
+the	O
+same	O
+family	O
+.	O
+
+Among	O
+mammalian	B-GENE
+HSFs	I-GENE
+,	O
+HSF1	B-GENE
+has	O
+been	O
+shown	O
+to	O
+be	O
+important	O
+for	O
+regulation	O
+of	O
+the	O
+heat	O
+-	O
+induced	O
+stress	O
+gene	O
+expression	O
+,	O
+whereas	O
+the	O
+function	O
+of	O
+HSF2	B-GENE
+in	O
+stress	O
+response	O
+is	O
+unclear	O
+.	O
+
+Importantly	O
+,	O
+concomitant	O
+expression	O
+of	O
+constitutive	O
+activated	O
+Raf	B-GENE
+and	O
+V12N38	B-GENE
+Ras	I-GENE
+results	O
+in	O
+almost	O
+complete	O
+loss	O
+of	O
+TTF	B-GENE
+-	I-GENE
+1	I-GENE
+activity	O
+.	O
+
+They	O
+share	O
+many	O
+downstream	O
+targets	O
+,	O
+including	O
+remodeling	O
+of	O
+the	O
+actin	B-GENE
+cytoskeleton	O
+,	O
+activation	O
+of	O
+p70	B-GENE
+(	I-GENE
+S6	I-GENE
+)	I-GENE
+kinase	I-GENE
+and	O
+c	B-GENE
+-	I-GENE
+jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+(	O
+JNK	B-GENE
+)	O
+,	O
+and	O
+regulation	O
+of	O
+transcription	O
+and	O
+cell	O
+proliferation	O
+.	O
+
+Expression	O
+of	O
+activated	O
+Cdc42	B-GENE
+results	O
+in	O
+the	O
+translocation	O
+of	O
+PKClambda	B-GENE
+from	O
+the	O
+nucleus	O
+into	O
+the	O
+cytosol	O
+,	O
+and	O
+Cdc42	B-GENE
+and	O
+PKClambda	B-GENE
+colocalize	O
+at	O
+the	O
+plasma	O
+membrane	O
+and	O
+in	O
+the	O
+cytoplasm	O
+.	O
+
+Copyright	O
+2000	O
+Academic	O
+Press	O
+.	O
+
+Southern	O
+blotting	O
+and	O
+single	O
+strand	O
+conformation	O
+polymorphism	O
+analyses	O
+did	O
+not	O
+show	O
+tumor	O
+-	O
+specific	O
+alterations	O
+of	O
+this	O
+gene	O
+in	O
+gliomas	O
+and	O
+RT	O
+-	O
+PCR	O
+studies	O
+showed	O
+expression	O
+in	O
+glioma	O
+cell	O
+lines	O
+,	O
+suggesting	O
+that	O
+ANOVA	B-GENE
+is	O
+not	O
+the	O
+chromosome	O
+19q	O
+glioma	O
+tumor	O
+suppressor	O
+gene	O
+.	O
+
+Enzyme	B-GENE
+I	I-GENE
+of	O
+the	O
+phosphoenolpyruvate	B-GENE
+:	I-GENE
+sugar	I-GENE
+phosphotransferase	I-GENE
+system	O
+.	O
+
+Based	O
+on	O
+these	O
+data	O
+,	O
+we	O
+conclude	O
+that	O
+transcription	O
+of	O
+prgX	B-GENE
+is	O
+initiated	O
+from	O
+the	O
+Qa	B-GENE
+promoter	I-GENE
+in	O
+prgQ	B-GENE
+,	O
+and	O
+PrgX	B-GENE
+autoregulates	O
+its	O
+transcription	O
+either	O
+by	O
+mediating	O
+transcriptional	O
+readthrough	O
+or	O
+increasing	O
+mRNA	O
+stability	O
+.	O
+
+It	O
+was	O
+established	O
+that	O
+intrathecal	O
+or	O
+intraperitoneal	O
+PTFL	O
+,	O
+elevated	O
+the	O
+nociceptive	O
+threshold	O
+for	O
+mechanical	O
+stimuli	O
+in	O
+the	O
+formalin	O
+test	O
+in	O
+rats	O
+.	O
+
+Molecular	O
+mimicry	O
+of	O
+human	O
+cytokine	O
+and	O
+cytokine	O
+response	O
+pathway	O
+genes	O
+by	O
+KSHV	O
+.	O
+
+Family	O
+environment	O
+was	O
+an	O
+important	O
+influence	O
+on	O
+interpersonal	O
+relationships	O
+,	O
+substance	O
+use	O
+,	O
+and	O
+social	O
+support	O
+.	O
+
+By	O
+electrophoresis	O
+mobility	O
+shift	O
+assays	O
+using	O
+probes	O
+corresponding	O
+to	O
+different	O
+segments	O
+of	O
+the	O
+putative	O
+human	B-GENE
+c	I-GENE
+-	I-GENE
+myb	I-GENE
+intron	I-GENE
+1	I-GENE
+transcription	I-GENE
+pause	I-GENE
+region	I-GENE
+and	O
+nuclear	O
+extracts	O
+from	O
+myeloid	O
+leukemia	O
+HL	O
+60	O
+and	O
+fibroblast	O
+WI	O
+38	O
+cells	O
+,	O
+we	O
+detected	O
+a	O
+HL	O
+-	O
+60	O
+-	O
+specific	O
+DNA	O
+-	O
+protein	O
+complex	O
+with	O
+a	O
+123	O
+-	O
+bp	O
+fragment	O
+containing	O
+binding	O
+sites	O
+for	O
+the	O
+interferon	B-GENE
+regulatory	I-GENE
+factors	I-GENE
+(	O
+IRFs	B-GENE
+)	O
+nuclear	O
+proteins	O
+.	O
+
+STUDY	O
+DESIGN	O
+:	O
+Fine	O
+needle	O
+aspiration	O
+cytologic	O
+smears	O
+from	O
+21	O
+cases	O
+of	O
+invasive	O
+lobular	O
+carcinoma	O
+(	O
+ILC	O
+)	O
+of	O
+breast	O
+were	O
+subjected	O
+to	O
+detailed	O
+cytomorphologic	O
+analysis	O
+.	O
+
+Electrophile	O
+Response	O
+Elements	O
+(	O
+EpREs	O
+)	O
+,	O
+located	O
+in	O
+5	O
+'	O
+-	O
+flanking	O
+sequences	O
+of	O
+both	O
+the	O
+GCSh	B-GENE
+and	O
+GCSl	B-GENE
+subunit	I-GENE
+genes	I-GENE
+,	O
+are	O
+hypothesized	O
+to	O
+at	O
+least	O
+partially	O
+mediate	O
+gene	O
+induction	O
+following	O
+xenobiotic	O
+exposure	O
+.	O
+
+A	O
+new	O
+technique	O
+to	O
+create	O
+an	O
+artificial	O
+stenosis	O
+in	O
+the	O
+native	O
+LAD	O
+using	O
+a	O
+hemoclip	O
+.	O
+
+Dll3	B-GENE
+is	O
+mutated	O
+in	O
+the	O
+X	O
+-	O
+ray	O
+-	O
+induced	O
+mouse	B-GENE
+mutant	I-GENE
+pudgy	I-GENE
+(	O
+pu	B-GENE
+)	O
+,	O
+causing	O
+a	O
+variety	O
+of	O
+vertebrocostal	O
+defects	O
+similar	O
+to	O
+SD	O
+phenotypes	O
+.	O
+
+TbRAB31	B-GENE
+behaviour	O
+was	O
+also	O
+studied	O
+during	O
+the	O
+cell	O
+cycle	O
+;	O
+TbRAB31	B-GENE
+always	O
+localised	O
+to	O
+a	O
+discrete	O
+structure	O
+that	O
+duplicated	O
+very	O
+early	O
+in	O
+mitosis	O
+and	O
+relocated	O
+to	O
+daughter	O
+cells	O
+in	O
+a	O
+coordinate	O
+manner	O
+with	O
+the	O
+basal	O
+body	O
+and	O
+kinetoplast	O
+,	O
+suggesting	O
+the	O
+involvement	O
+of	O
+microtubules	O
+.	O
+
+Invertases	B-GENE
+are	O
+responsible	O
+for	O
+the	O
+breakdown	O
+of	O
+sucrose	O
+to	O
+fructose	O
+and	O
+glucose	O
+.	O
+
+To	O
+investigate	O
+the	O
+molecular	O
+mechanisms	O
+of	O
+this	O
+Tax	B-GENE
+-	O
+mediated	O
+inhibition	O
+,	O
+we	O
+analyzed	O
+its	O
+effect	O
+on	O
+the	O
+transcriptional	O
+activity	O
+of	O
+the	O
+myogenic	O
+MyoD	B-GENE
+protein	I-GENE
+,	O
+which	O
+was	O
+used	O
+as	O
+a	O
+paradigm	O
+of	O
+bHLH	B-GENE
+factors	I-GENE
+.	O
+
+The	O
+human	B-GENE
+T	I-GENE
+cell	I-GENE
+leukemia	I-GENE
+/	I-GENE
+lymphotropic	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+Tax	I-GENE
+protein	I-GENE
+represses	O
+MyoD	B-GENE
+-	O
+dependent	O
+transcription	O
+by	O
+inhibiting	O
+MyoD	B-GENE
+-	O
+binding	O
+to	O
+the	O
+KIX	B-GENE
+domain	I-GENE
+of	O
+p300	B-GENE
+.	O
+
+Phosphorylation	O
+and	O
+spindle	O
+pole	O
+body	O
+localization	O
+of	O
+the	O
+Cdc15p	B-GENE
+mitotic	I-GENE
+regulatory	I-GENE
+protein	I-GENE
+kinase	I-GENE
+in	I-GENE
+budding	I-GENE
+yeast	I-GENE
+.	O
+
+Thus	O
+,	O
+both	O
+the	O
+hyperplasia	O
+and	O
+thrombotic	O
+complications	O
+which	O
+often	O
+follow	O
+stenting	O
+might	O
+be	O
+minimized	O
+by	O
+employing	O
+gold	O
+stents	O
+,	O
+which	O
+have	O
+a	O
+greater	O
+capacity	O
+than	O
+steel	O
+in	O
+supporting	O
+a	O
+functional	O
+neo	O
+-	O
+endothelium	O
+.	O
+
+The	O
+cell	O
+cycle	O
+and	O
+transcriptional	O
+defects	O
+caused	O
+by	O
+taf17	B-GENE
+(	O
+slm7	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+are	O
+consistent	O
+with	O
+the	O
+role	O
+of	O
+TAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+s	I-GENE
+as	O
+modulators	O
+of	O
+transcriptional	O
+activation	O
+and	O
+may	O
+reflect	O
+a	O
+role	O
+for	O
+TAF17	B-GENE
+in	O
+regulating	O
+activation	O
+by	O
+SBF	B-GENE
+and	O
+MBF	B-GENE
+.	O
+
+Proteolysis	O
+of	O
+Mbp1	B-GENE
+and	O
+Swi4	B-GENE
+DNA	I-GENE
+-	I-GENE
+protein	I-GENE
+complexes	I-GENE
+has	O
+revealed	O
+the	O
+extent	O
+of	O
+these	O
+sequences	O
+,	O
+and	O
+C	O
+-	O
+terminally	O
+extended	O
+molecules	O
+with	O
+substantially	O
+enhanced	O
+DNA	O
+binding	O
+activity	O
+compared	O
+to	O
+the	O
+core	O
+domains	O
+alone	O
+have	O
+been	O
+produced	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+residue	O
+266	O
+serves	O
+as	O
+a	O
+"	O
+protein	O
+sensor	O
+"	O
+of	O
+altered	O
+minor	O
+groove	O
+interactions	O
+and	O
+identifies	O
+which	O
+base	O
+pair	O
+interactions	O
+are	O
+altered	O
+by	O
+these	O
+lesions	O
+.	O
+
+The	O
+recombinant	O
+enzymes	O
+exist	O
+as	O
+monomers	O
+.	O
+
+A	O
+pathway	O
+for	O
+regulation	O
+of	O
+B	B-GENE
+lymphocyte	I-GENE
+antigen	I-GENE
+receptor	I-GENE
+-	O
+induced	O
+calcium	O
+flux	O
+.	O
+
+We	O
+now	O
+describe	O
+a	O
+second	O
+RIM	B-GENE
+protein	I-GENE
+,	O
+called	O
+RIM2	B-GENE
+,	O
+that	O
+is	O
+highly	O
+homologous	O
+to	O
+RIM1	B-GENE
+and	O
+also	O
+expressed	O
+primarily	O
+in	O
+brain	O
+.	O
+
+Inhibitor	B-GENE
+-	I-GENE
+1	I-GENE
+(	O
+I	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+inhibitor	B-GENE
+-	I-GENE
+2	I-GENE
+(	O
+I	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+selectively	O
+inhibit	O
+type	B-GENE
+1	I-GENE
+protein	I-GENE
+serine	I-GENE
+/	I-GENE
+threonine	I-GENE
+phosphatases	I-GENE
+(	O
+PP1	B-GENE
+)	O
+.	O
+
+The	O
+substrates	O
+for	O
+glycan	O
+synthesis	O
+in	O
+the	O
+lumen	O
+of	O
+the	O
+Golgi	O
+are	O
+nucleotide	O
+sugars	O
+that	O
+must	O
+be	O
+transported	O
+from	O
+the	O
+cytosol	O
+by	O
+specific	O
+membrane	O
+-	O
+bound	O
+transporters	O
+.	O
+
+Synaptic	O
+targeting	O
+of	O
+the	O
+postsynaptic	B-GENE
+density	I-GENE
+protein	I-GENE
+PSD	I-GENE
+-	I-GENE
+95	I-GENE
+mediated	O
+by	O
+a	O
+tyrosine	O
+-	O
+based	O
+trafficking	O
+signal	O
+.	O
+
+(	O
+1998	O
+)	O
+J	O
+.	O
+
+Both	O
+normal	O
+and	O
+transforming	O
+PCPH	B-GENE
+proteins	I-GENE
+have	O
+guanosine	B-GENE
+diphosphatase	I-GENE
+activity	O
+but	O
+only	O
+the	O
+oncoprotein	O
+cooperates	O
+with	O
+Ras	B-GENE
+in	O
+activating	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+ERK1	B-GENE
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+virulence	O
+-	O
+associated	O
+genes	O
+and	O
+their	O
+overall	O
+chromosomal	O
+arrangement	O
+are	O
+relatively	O
+well	O
+conserved	O
+between	O
+B	O
+.	O
+henselae	O
+and	O
+other	O
+gram	O
+-	O
+negative	O
+bacteria	O
+such	O
+as	O
+A	O
+.	O
+tumefaciens	O
+.	O
+
+An	O
+important	O
+mechanism	O
+by	O
+which	O
+the	O
+tumor	O
+suppressor	O
+p53	B-GENE
+maintains	O
+genomic	O
+stability	O
+is	O
+to	O
+induce	O
+cell	O
+cycle	O
+arrest	O
+through	O
+activation	O
+of	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+inhibitor	O
+p21	B-GENE
+(	O
+WAF1	B-GENE
+/	O
+Cip1	B-GENE
+)	O
+gene	O
+.	O
+
+Paxillin	B-GENE
+acts	O
+as	O
+an	O
+adaptor	O
+molecule	O
+in	O
+integrin	B-GENE
+signaling	O
+.	O
+
+Thus	O
+,	O
+growth	O
+factor	O
+activation	O
+of	O
+ER	B-GENE
+can	O
+mediate	O
+transactivation	O
+vs	O
+ER	B-GENE
+/	O
+Sp1	B-GENE
+binding	O
+to	O
+GC	O
+-	O
+rich	O
+sites	O
+and	O
+represents	O
+a	O
+novel	O
+pathway	O
+for	O
+ligand	O
+-	O
+independent	O
+ER	B-GENE
+action	O
+.	O
+
+Furthermore	O
+,	O
+analysis	O
+of	O
+deletion	O
+promoter	O
+-	O
+reporter	O
+constructs	O
+found	O
+that	O
+the	O
+basal	O
+activity	O
+of	O
+P2	O
+resided	O
+in	O
+the	O
+proximal	O
+region	O
+of	O
+P2	O
+.	O
+
+RESULTS	O
+:	O
+Auditory	O
+thresholds	O
+collected	O
+during	O
+audiometric	O
+tests	O
+increased	O
+gradually	O
+in	O
+proportion	O
+with	O
+age	O
+,	O
+especially	O
+in	O
+the	O
+hypertensive	O
+group	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+transcription	O
+of	O
+c	B-GENE
+-	I-GENE
+IAP2	I-GENE
+promoter	I-GENE
+was	O
+strongly	O
+up	O
+-	O
+regulated	O
+when	O
+CD40	B-GENE
+or	O
+Epstein	B-GENE
+-	I-GENE
+Barr	I-GENE
+virus	I-GENE
+latent	I-GENE
+membrane	I-GENE
+protein	I-GENE
+1	I-GENE
+was	O
+overexpressed	O
+.	O
+
+A	O
+variety	O
+of	O
+professional	O
+and	O
+self	O
+-	O
+applied	O
+fluoride	O
+products	O
+are	O
+available	O
+and	O
+new	O
+fluoride	O
+delivery	O
+systems	O
+have	O
+recently	O
+entered	O
+the	O
+market	O
+.	O
+
+These	O
+studies	O
+identify	O
+several	O
+of	O
+the	O
+signal	O
+-	O
+transduction	O
+events	O
+involved	O
+in	O
+the	O
+apoptosis	O
+of	O
+malignant	O
+B	O
+cells	O
+that	O
+transpire	O
+following	O
+ligation	O
+of	O
+CD20	B-GENE
+by	O
+anti	B-GENE
+-	I-GENE
+CD20	I-GENE
+antibodies	I-GENE
+in	O
+the	O
+presence	O
+of	O
+Fc	B-GENE
+-	I-GENE
+receptor	I-GENE
+-	O
+expressing	O
+cells	O
+or	O
+secondary	O
+goat	O
+anti	B-GENE
+-	I-GENE
+(	I-GENE
+mouse	I-GENE
+Ig	I-GENE
+)	I-GENE
+antibodies	I-GENE
+and	O
+which	O
+may	O
+contribute	O
+to	O
+the	O
+tumor	O
+regressions	O
+observed	O
+in	O
+mouse	O
+models	O
+and	O
+clinical	O
+trials	O
+.	O
+
+Phenazone	O
+potentiates	O
+the	O
+local	O
+anaesthetic	O
+effect	O
+of	O
+lidocaine	O
+in	O
+mice	O
+.	O
+
+The	O
+solubility	O
+of	O
+all	O
+the	O
+mutated	O
+proteins	O
+was	O
+remarkably	O
+reduced	O
+.	O
+
+Recently	O
+,	O
+identical	O
+RBE	B-GENE
+sequences	I-GENE
+have	O
+been	O
+identified	O
+at	O
+other	O
+locations	O
+in	O
+the	O
+human	O
+genome	O
+.	O
+
+EM	O
+analysis	O
+demonstrated	O
+that	O
+only	O
+one	O
+Rep	B-GENE
+-	I-GENE
+DNA	I-GENE
+complex	I-GENE
+was	O
+formed	O
+on	O
+ch	O
+-	O
+19	O
+target	O
+DNA	O
+.	O
+
+The	O
+protein	O
+was	O
+associated	O
+with	O
+purified	O
+vaccinia	O
+virus	O
+particles	O
+and	O
+with	O
+membranes	O
+of	O
+immature	O
+and	O
+mature	O
+virions	O
+that	O
+were	O
+visualized	O
+by	O
+electron	O
+microscopy	O
+of	O
+infected	O
+cells	O
+.	O
+
+CONCLUSION	O
+:	O
+More	O
+than	O
+50	O
+%	O
+of	O
+patients	O
+with	O
+perennial	O
+rhinitis	O
+and	O
+CRS	O
+do	O
+not	O
+improve	O
+after	O
+surgery	O
+,	O
+a	O
+response	O
+that	O
+may	O
+be	O
+predicted	O
+by	O
+more	O
+cells	O
+expressing	O
+IL	B-GENE
+-	I-GENE
+5	I-GENE
+mRNA	I-GENE
+in	O
+the	O
+ethmoid	O
+sinuses	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+size	O
+,	O
+the	O
+CRS	O
+sequence	O
+to	O
+which	O
+it	O
+binds	O
+,	O
+and	O
+its	O
+tentative	O
+identification	O
+as	O
+a	O
+zinc	B-GENE
+finger	I-GENE
+protein	I-GENE
+,	O
+Adx	B-GENE
+factor	I-GENE
+has	O
+been	O
+identified	O
+as	O
+a	O
+Kruppel	B-GENE
+-	I-GENE
+like	I-GENE
+zinc	I-GENE
+finger	I-GENE
+protein	I-GENE
+(	O
+a	O
+mouse	B-GENE
+ZBP	I-GENE
+-	I-GENE
+89	I-GENE
+homologue	I-GENE
+)	O
+.	O
+
+METHODS	O
+:	O
+The	O
+most	O
+distal	O
+muscle	O
+fibres	O
+from	O
+the	O
+deep	O
+and	O
+superficial	O
+finger	O
+flexors	O
+were	O
+measured	O
+relative	O
+to	O
+the	O
+pisiform	O
+bone	O
+in	O
+18	O
+cadaveric	O
+specimens	O
+.	O
+
+Here	O
+we	O
+report	O
+on	O
+the	O
+isolation	O
+of	O
+ICK2	B-GENE
+,	O
+and	O
+show	O
+that	O
+it	O
+interacts	O
+with	O
+Cdc2aAt	B-GENE
+,	O
+but	O
+not	O
+with	O
+a	O
+second	O
+CDK	B-GENE
+from	I-GENE
+Arabidopsis	I-GENE
+,	O
+Cdc2bAt	B-GENE
+.	O
+
+Systemic	O
+impact	O
+of	O
+risk	O
+-	O
+sharing	O
+arrangements	O
+.	O
+
+METHODS	O
+:	O
+We	O
+determined	O
+an	O
+odds	O
+ratio	O
+(	O
+OR	O
+)	O
+,	O
+as	O
+a	O
+measure	O
+of	O
+the	O
+relative	O
+risk	O
+of	O
+being	O
+exposed	O
+to	O
+a	O
+potential	O
+interaction	O
+,	O
+comparing	O
+the	O
+use	O
+of	O
+the	O
+H2	B-GENE
+-	I-GENE
+receptor	I-GENE
+antagonist	O
+,	O
+cimetidine	O
+,	O
+with	O
+that	O
+of	O
+the	O
+noninteracting	O
+agents	O
+ranitidine	O
+,	O
+famotidine	O
+and	O
+nizatidine	O
+in	O
+users	O
+and	O
+nonusers	O
+of	O
+warfarin	O
+,	O
+phenytoin	O
+and	O
+theophylline	O
+.	O
+
+The	O
+prevalence	O
+of	O
+malnutrition	O
+was	O
+30	O
+%	O
+in	O
+the	O
+47	O
+patients	O
+without	O
+CVD	O
+and	O
+was	O
+significantly	O
+higher	O
+(	O
+70	O
+%	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+the	O
+70	O
+patients	O
+with	O
+CVD	O
+,	O
+who	O
+also	O
+had	O
+lower	O
+tHcy	O
+,	O
+SAlb	O
+,	O
+plasma	B-GENE
+IGF	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+serum	O
+creatinine	O
+(	O
+SCr	O
+)	O
+,	O
+and	O
+blood	B-GENE
+hemoglobin	I-GENE
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+,	O
+at	O
+least	O
+at	O
+high	O
+temperature	O
+,	O
+a	O
+critical	O
+minimal	O
+level	O
+of	O
+Ypt	B-GENE
+protein	I-GENE
+prenylation	O
+is	O
+required	O
+for	O
+maintaining	O
+vesicle	O
+polarization	O
+.	O
+
+The	O
+second	O
+functional	O
+pair	O
+of	O
+CreA	B-GENE
+sites	I-GENE
+is	O
+located	O
+between	O
+the	O
+two	O
+transcription	O
+initiation	O
+sites	O
+.	O
+
+A	O
+distinct	O
+staining	O
+pattern	O
+for	O
+the	O
+N	B-GENE
+-	I-GENE
+utrophin	I-GENE
+was	O
+not	O
+detectable	O
+,	O
+although	O
+it	O
+was	O
+expected	O
+to	O
+localise	O
+at	O
+the	O
+actin	B-GENE
+stress	O
+fibers	O
+.	O
+
+The	O
+'	O
+Newcastle	O
+'	O
+model	O
+,	O
+which	O
+is	O
+based	O
+on	O
+Hotelling	O
+'	O
+s	O
+T2	O
+statistic	O
+,	O
+proved	O
+to	O
+be	O
+more	O
+sensitive	O
+and	O
+diagnosed	O
+a	O
+systematic	O
+displacement	O
+for	O
+three	O
+prostate	O
+patients	O
+.	O
+
+The	O
+MMA	B-GENE
+,	I-GENE
+DMA	I-GENE
+,	I-GENE
+and	I-GENE
+TMA	I-GENE
+methyltransferases	I-GENE
+are	O
+not	O
+homologs	O
+;	O
+however	O
+,	O
+like	O
+the	O
+MMA	B-GENE
+methyltransferase	I-GENE
+gene	I-GENE
+,	O
+the	O
+genes	O
+encoding	O
+the	O
+DMA	B-GENE
+and	I-GENE
+TMA	I-GENE
+methyltransferases	I-GENE
+each	O
+contain	O
+a	O
+single	O
+in	O
+-	O
+frame	O
+amber	O
+codon	O
+.	O
+
+After	O
+phosphorylation	O
+,	O
+STAT	B-GENE
+proteins	I-GENE
+are	O
+transported	O
+into	O
+the	O
+nucleus	O
+and	O
+exhibit	O
+transcriptional	O
+activity	O
+.	O
+
+Overexpression	O
+of	O
+mcl	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+sufficient	O
+to	O
+protect	O
+against	O
+apoptosis	O
+,	O
+while	O
+transfection	O
+of	O
+a	O
+mcl	B-GENE
+-	I-GENE
+1	I-GENE
+antisense	O
+plasmid	O
+causes	O
+cell	O
+death	O
+.	O
+
+Thus	O
+,	O
+although	O
+multiple	O
+senescence	O
+pathways	O
+are	O
+activated	O
+in	O
+response	O
+to	O
+a	O
+ras	B-GENE
+oncogene	I-GENE
+,	O
+inactivation	O
+of	O
+TGFbeta1	B-GENE
+secretion	O
+or	O
+response	O
+is	O
+sufficient	O
+to	O
+block	O
+the	O
+senescence	O
+program	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+abilities	O
+of	O
+constitutive	O
+and	O
+conditional	O
+forms	O
+of	O
+the	O
+three	O
+Raf	B-GENE
+kinases	I-GENE
+to	O
+abrogate	O
+the	O
+cytokine	O
+dependency	O
+of	O
+FDC	O
+-	O
+P1	O
+cells	O
+were	O
+examined	O
+.	O
+
+Application	O
+of	O
+the	O
+method	O
+to	O
+a	O
+representative	O
+set	O
+of	O
+50	O
+known	O
+genes	O
+from	O
+Arabidopsis	O
+thaliana	O
+showed	O
+significant	O
+improvement	O
+in	O
+prediction	O
+accuracy	O
+compared	O
+to	O
+previous	O
+spliced	O
+alignment	O
+methods	O
+.	O
+
+The	O
+complete	O
+cDNA	O
+sequence	O
+of	O
+human	B-GENE
+betaV	I-GENE
+spectrin	I-GENE
+is	O
+available	O
+from	O
+GenBank	O
+(	O
+TM	O
+)	O
+as	O
+accession	O
+number	O
+.	O
+
+Transactivation	O
+of	O
+naturally	O
+occurring	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+long	I-GENE
+terminal	I-GENE
+repeats	I-GENE
+by	O
+the	O
+JNK	B-GENE
+signaling	O
+pathway	O
+.	O
+
+The	O
+mode	O
+of	O
+resistance	O
+to	O
+quinupristin	O
+/	O
+dalfopristin	O
+was	O
+not	O
+evident	O
+(	O
+sat	O
+A	O
+-	O
+negative	O
+by	O
+PCR	O
+)	O
+;	O
+and	O
+these	O
+cases	O
+illustrate	O
+the	O
+existence	O
+of	O
+streptogramin	O
+-	O
+resistant	O
+isolates	O
+before	O
+the	O
+introduction	O
+of	O
+this	O
+antimicrobial	O
+class	O
+into	O
+human	O
+clinical	O
+practice	O
+.	O
+
+This	O
+study	O
+was	O
+carried	O
+out	O
+to	O
+analyze	O
+PRL	B-GENE
+secretion	O
+in	O
+metastatic	O
+prostate	O
+cancer	O
+patients	O
+both	O
+at	O
+basal	O
+conditions	O
+and	O
+in	O
+response	O
+to	O
+L	O
+-	O
+Dopa	O
+and	O
+metoclopramide	O
+,	O
+which	O
+represents	O
+the	O
+most	O
+classical	O
+inhibitory	O
+and	O
+stimulatory	O
+tests	O
+for	O
+PRL	B-GENE
+secretion	O
+,	O
+respectively	O
+.	O
+
+Integrin	B-GENE
+adhesion	I-GENE
+receptors	I-GENE
+transduce	O
+signals	O
+that	O
+control	O
+complex	O
+cell	O
+functions	O
+which	O
+require	O
+the	O
+regulation	O
+of	O
+gene	O
+expression	O
+,	O
+such	O
+as	O
+proliferation	O
+,	O
+differentiation	O
+and	O
+survival	O
+.	O
+
+Recombination	O
+,	O
+replication	O
+,	O
+repair	O
+:	O
+from	O
+complexity	O
+to	O
+harmony	O
+.	O
+
+Hex	B-GENE
+is	O
+expressed	O
+in	O
+the	O
+developing	O
+liver	O
+coincident	O
+with	O
+the	O
+forkhead	B-GENE
+/	O
+winged	B-GENE
+helix	I-GENE
+transcription	O
+factor	O
+,	O
+Hepatocyte	B-GENE
+Nuclear	I-GENE
+Factor	I-GENE
+3beta	I-GENE
+(	O
+HNF3beta	B-GENE
+)	O
+.	O
+
+As	O
+an	O
+extension	O
+of	O
+our	O
+structural	O
+characterization	O
+of	O
+the	O
+exon	O
+-	O
+intron	O
+organization	O
+of	O
+the	O
+mouse	B-GENE
+Pkr	I-GENE
+gene	I-GENE
+,	O
+we	O
+now	O
+have	O
+isolated	O
+and	O
+characterized	O
+the	O
+mouse	B-GENE
+Pkr	I-GENE
+promoter	I-GENE
+region	I-GENE
+required	O
+for	O
+IFN	B-GENE
+-	O
+inducible	O
+transcription	O
+.	O
+
+The	O
+CRE	O
+,	O
+5	O
+'	O
+-	O
+TGACGTCA	O
+-	O
+3	O
+'	O
+,	O
+has	O
+been	O
+described	O
+as	O
+the	O
+consensus	O
+sequence	O
+for	O
+the	O
+cis	O
+-	O
+element	O
+that	O
+directs	O
+cAMP	O
+-	O
+regulated	O
+gene	O
+expression	O
+.	O
+
+Kidney	O
+length	O
+did	O
+not	O
+significantly	O
+differ	O
+between	O
+right	O
+and	O
+left	O
+,	O
+however	O
+,	O
+kidney	O
+width	O
+,	O
+cortical	O
+thickness	O
+and	O
+size	O
+did	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+clinical	O
+stage	O
+was	O
+I	O
+(	O
+T1N0M0	O
+)	O
+,	O
+and	O
+S2	O
+sleeve	O
+segmentectomy	O
+with	O
+lymph	O
+node	O
+dissection	O
+(	O
+R	O
+2	O
+b	O
+)	O
+was	O
+performed	O
+.	O
+
+Benztropine	O
+for	O
+venlafaxine	O
+-	O
+induced	O
+night	O
+sweats	O
+.	O
+
+The	O
+physicians	O
+in	O
+charge	O
+of	O
+all	O
+patients	O
+with	O
+evidence	O
+of	O
+acute	O
+Q	O
+fever	O
+(	O
+seroconversion	O
+and	O
+/	O
+or	O
+presence	O
+of	O
+IgM	B-GENE
+)	O
+or	O
+chronic	O
+Q	O
+fever	O
+(	O
+prolonged	O
+disease	O
+and	O
+/	O
+or	O
+IgG	B-GENE
+antibody	I-GENE
+titer	O
+to	O
+phase	O
+I	O
+of	O
+Coxiella	O
+burnetii	O
+>	O
+or	O
+=	O
+800	O
+)	O
+were	O
+asked	O
+to	O
+complete	O
+a	O
+questionnaire	O
+,	O
+which	O
+was	O
+computerized	O
+.	O
+
+Copyright	O
+2000	O
+Academic	O
+Press	O
+.	O
+
+Viral	O
+cell	O
+-	O
+to	O
+-	O
+cell	O
+movement	O
+of	O
+PVX	B-GENE
+CP	I-GENE
+mutant	I-GENE
+was	O
+complemented	O
+in	O
+Nicotiana	O
+tabacum	O
+cv	O
+.	O
+
+Induction	O
+of	O
+CD86	B-GENE
+expression	O
+by	O
+stimulation	O
+of	O
+U937	O
+cells	O
+with	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+revealed	O
+the	O
+presence	O
+of	O
+two	O
+functional	O
+GAS	B-GENE
+(	O
+gamma	B-GENE
+-	I-GENE
+interferon	I-GENE
+activation	I-GENE
+site	I-GENE
+)	O
+elements	O
+.	O
+
+SNAP	B-GENE
+-	I-GENE
+23	I-GENE
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+vesicle	O
+trafficking	O
+in	O
+mammalian	O
+cells	O
+.	O
+
+Ab	O
+-	O
+MLV	O
+strains	O
+expressing	O
+P70	B-GENE
+/	O
+S2	B-GENE
+failed	O
+to	O
+transform	O
+NIH	O
+3T3	O
+cells	O
+and	O
+demonstrated	O
+a	O
+greatly	O
+reduced	O
+capacity	O
+to	O
+mediate	O
+signaling	O
+events	O
+associated	O
+with	O
+the	O
+Ras	B-GENE
+-	O
+dependent	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinase	I-GENE
+pathway	O
+.	O
+
+The	O
+p53	B-GENE
+-	I-GENE
+homolog	I-GENE
+p73beta	B-GENE
+also	O
+activated	O
+the	O
+PIG3	B-GENE
+promoter	I-GENE
+,	O
+but	O
+in	O
+contrast	O
+to	O
+p53	B-GENE
+,	O
+the	O
+proline	O
+-	O
+rich	O
+domain	O
+of	O
+p73beta	B-GENE
+(	I-GENE
+residues	I-GENE
+81	I-GENE
+-	I-GENE
+113	I-GENE
+)	I-GENE
+was	O
+dispensable	O
+to	O
+induce	O
+the	O
+PIG3	B-GENE
+promoter	I-GENE
+.	O
+
+Results	O
+from	O
+transient	O
+assays	O
+using	O
+these	O
+mutants	O
+showed	O
+that	O
+the	O
+DE1	O
+received	O
+signals	O
+from	O
+phytochromes	B-GENE
+A	I-GENE
+and	I-GENE
+B	I-GENE
+,	O
+demonstrating	O
+that	O
+this	O
+element	O
+is	O
+indeed	O
+a	O
+light	O
+-	O
+responsive	O
+element	O
+.	O
+
+Co	O
+-	O
+immunoprecipitation	O
+and	O
+DNA	O
+affinity	O
+chromatography	O
+prove	O
+that	O
+Sp1	B-GENE
+heterodimerizes	O
+with	O
+ZBP	B-GENE
+-	I-GENE
+89	I-GENE
+when	O
+bound	O
+to	O
+the	O
+silencer	O
+element	O
+to	O
+yield	O
+a	O
+DNA	O
+-	O
+protein	O
+complex	O
+whose	O
+mobility	O
+is	O
+indistinguishable	O
+from	O
+that	O
+displayed	O
+by	O
+HeLa	O
+nuclear	O
+extract	O
+in	O
+band	O
+shift	O
+assays	O
+.	O
+
+The	O
+ZNF274	B-GENE
+gene	I-GENE
+is	O
+mapped	O
+distal	O
+to	O
+marker	O
+RP	O
+S28	O
+1	O
+in	O
+the	O
+human	O
+chromosome	O
+19qter	O
+region	O
+,	O
+by	O
+RH	O
+mapping	O
+.	O
+
+The	O
+C	B-GENE
+-	I-GENE
+terminal	I-GENE
+Cdk2	I-GENE
+truncations	O
+,	O
+however	O
+,	O
+were	O
+non	O
+-	O
+functional	O
+in	O
+these	O
+strains	O
+and	O
+thus	O
+dependent	O
+for	O
+activity	O
+on	O
+the	O
+pho85	B-GENE
+coding	I-GENE
+region	I-GENE
+which	O
+remained	O
+in	O
+the	O
+mutant	B-GENE
+pho85	I-GENE
+:	O
+:	O
+HIS3	B-GENE
+chromosomal	I-GENE
+locus	I-GENE
+.	O
+
+We	O
+report	O
+here	O
+on	O
+the	O
+molecular	O
+nature	O
+of	O
+an	O
+EMS	O
+-	O
+induced	O
+mutant	O
+,	O
+mn1	B-GENE
+-	I-GENE
+89	I-GENE
+,	O
+a	O
+leaky	O
+semidominant	O
+allele	O
+of	O
+the	O
+Miniature1	B-GENE
+(	O
+Mn1	B-GENE
+)	O
+seed	O
+locus	O
+that	O
+encodes	O
+a	O
+seed	B-GENE
+-	I-GENE
+specific	I-GENE
+cell	I-GENE
+wall	I-GENE
+invertase	I-GENE
+,	O
+INCW2	B-GENE
+.	O
+
+We	O
+conclude	O
+that	O
+,	O
+both	O
+in	O
+atrial	O
+myocytes	O
+and	O
+in	O
+Xenopus	O
+oocytes	O
+,	O
+beta	O
+-	O
+adrenergic	O
+stimulation	O
+potentiates	O
+the	O
+ACh	O
+-	O
+evoked	O
+GIRK	B-GENE
+channels	I-GENE
+via	O
+a	O
+pathway	O
+that	O
+involves	O
+PKA	B-GENE
+-	O
+catalyzed	O
+phosphorylation	O
+downstream	O
+from	O
+beta	B-GENE
+(	I-GENE
+2	I-GENE
+)	I-GENE
+AR	I-GENE
+.	O
+
+Identification	O
+of	O
+a	O
+novel	O
+E2F3	B-GENE
+product	I-GENE
+suggests	O
+a	O
+mechanism	O
+for	O
+determining	O
+specificity	O
+of	O
+repression	O
+by	O
+Rb	B-GENE
+proteins	I-GENE
+.	O
+
+In	O
+DNase	B-GENE
+I	I-GENE
+footprinting	O
+protection	O
+analysis	O
+,	O
+both	O
+SFRE	B-GENE
+and	O
+ERE	O
+regions	O
+were	O
+protected	O
+by	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+-	O
+ERRalpha1	B-GENE
+fusion	O
+protein	O
+.	O
+
+Overexpressing	O
+the	O
+coactivator	O
+,	O
+SRC1a	B-GENE
+or	O
+GRIP1	B-GENE
+,	O
+further	O
+enhances	O
+ERRalpha1	B-GENE
+-	O
+induced	O
+transcriptional	O
+activity	O
+.	O
+
+Estrogen	B-GENE
+receptor	I-GENE
+-	I-GENE
+related	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+1	I-GENE
+interacts	O
+with	O
+coactivator	O
+and	O
+constitutively	O
+activates	O
+the	O
+estrogen	O
+response	O
+elements	O
+of	O
+the	O
+human	B-GENE
+lactoferrin	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+median	O
+levels	O
+of	O
+particles	O
+with	O
+50	O
+%	O
+cut	O
+-	O
+off	O
+aerodynamic	O
+diameters	O
+of	O
+10	O
+(	O
+PM10	O
+)	O
+and	O
+2	O
+.	O
+5	O
+microm	O
+(	O
+PM2	O
+.	O
+5	O
+)	O
+were	O
+170	O
+(	O
+range	O
+103	O
+-	O
+613	O
+)	O
+and	O
+95	O
+(	O
+range	O
+61	O
+-	O
+218	O
+)	O
+micro	O
+x	O
+m	O
+-	O
+3	O
+,	O
+respectively	O
+.	O
+
+Specific	O
+and	O
+heritable	O
+genetic	O
+interference	O
+by	O
+double	O
+-	O
+stranded	O
+RNA	O
+in	O
+Arabidopsis	O
+thaliana	O
+.	O
+
+Comparison	O
+of	O
+sequences	O
+from	O
+-	O
+215	O
+to	O
++	O
+1	O
+bp	O
+identified	O
+consensus	O
+binding	O
+sites	O
+for	O
+the	O
+homeodomain	B-GENE
+transcription	I-GENE
+factor	I-GENE
+thyroid	B-GENE
+transcription	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+TTF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+Two	O
+additional	O
+cis	O
+-	O
+acting	O
+sequences	O
+,	O
+conserved	O
+in	O
+both	O
+the	O
+region	O
+1	O
+and	O
+3	O
+promoters	O
+,	O
+were	O
+identified	O
+,	O
+suggesting	O
+a	O
+role	O
+for	O
+these	O
+sequences	O
+in	O
+the	O
+coordinate	O
+regulation	O
+of	O
+transcription	O
+from	O
+these	O
+promoters	O
+.	O
+
+Purple	O
+photosynthetic	O
+bacteria	O
+are	O
+capable	O
+of	O
+generating	O
+cellular	O
+energy	O
+from	O
+several	O
+sources	O
+,	O
+including	O
+photosynthesis	O
+,	O
+respiration	O
+,	O
+and	O
+H	O
+(	O
+2	O
+)	O
+oxidation	O
+.	O
+
+An	O
+analysis	O
+of	O
+synthetic	O
+peptides	O
+revealed	O
+a	O
+minimal	O
+CTD	O
+sequence	O
+that	O
+is	O
+sufficient	O
+to	O
+bind	O
+to	O
+the	O
+second	O
+Rsp5	B-GENE
+WW	I-GENE
+domain	I-GENE
+(	O
+Rsp5	B-GENE
+WW2	I-GENE
+)	O
+in	O
+vitro	O
+and	O
+in	O
+yeast	O
+two	O
+-	O
+hybrid	O
+assays	O
+.	O
+
+Furthermore	O
+,	O
+bone	O
+marrow	O
+-	O
+derived	O
+macrophages	O
+from	O
+LAT	B-GENE
+-	O
+deficient	O
+mice	O
+displayed	O
+reduced	O
+phagocytic	O
+efficiency	O
+in	O
+comparison	O
+to	O
+the	O
+macrophages	O
+from	O
+wild	O
+-	O
+type	O
+mice	O
+.	O
+
+T1	O
+-	O
+weighted	O
+MRI	O
+on	O
+the	O
+49th	O
+postoperative	O
+day	O
+demonstrated	O
+bilateral	O
+and	O
+symmetrical	O
+hyperintense	O
+lesions	O
+in	O
+the	O
+globus	O
+pallidus	O
+.	O
+
+The	O
+method	O
+is	O
+applied	O
+to	O
+determine	O
+aberration	O
+constants	O
+of	O
+a	O
+CM300	O
+FEG	O
+/	O
+UT	O
+microscope	O
+with	O
+correction	O
+of	O
+the	O
+three	O
+-	O
+fold	O
+astigmatism	O
+.	O
+
+The	O
+interaction	O
+does	O
+not	O
+depend	O
+on	O
+the	O
+presence	O
+of	O
+the	O
+correct	O
+amino	O
+-	O
+terminal	O
+DNA	O
+binding	O
+domain	O
+or	O
+the	O
+amino	O
+acid	O
+sequences	O
+between	O
+the	O
+DNA	O
+binding	O
+domain	O
+and	O
+the	O
+last	O
+ten	O
+amino	O
+acids	O
+.	O
+
+METHOD	O
+:	O
+The	O
+sample	O
+of	O
+subjects	O
+was	O
+drawn	O
+from	O
+the	O
+Suffolk	O
+County	O
+Mental	O
+Health	O
+Project	O
+,	O
+a	O
+longitudinal	O
+epidemiologic	O
+study	O
+of	O
+first	O
+-	O
+hospitalized	O
+subjects	O
+with	O
+psychotic	O
+disorders	O
+;	O
+the	O
+present	O
+study	O
+focused	O
+on	O
+patients	O
+with	O
+schizophrenic	O
+disorders	O
+.	O
+
+Marrow	O
+dysplasia	O
+is	O
+a	O
+major	O
+characteristic	O
+of	O
+patients	O
+with	O
+myelodysplastic	O
+syndrome	O
+(	O
+MDS	O
+)	O
+,	O
+along	O
+with	O
+marrow	O
+blastosis	O
+,	O
+cytopenia	O
+and	O
+cytogenetic	O
+anomalies	O
+.	O
+
+Eight	O
+of	O
+the	O
+non	O
+-	O
+acceptable	O
+inlays	O
+/	O
+onlays	O
+and	O
+five	O
+of	O
+the	O
+direct	O
+restorations	O
+were	O
+replaced	O
+,	O
+while	O
+the	O
+other	O
+ones	O
+were	O
+repaired	O
+with	O
+resin	O
+composite	O
+.	O
+
+How	O
+plants	O
+respond	O
+to	O
+attack	O
+by	O
+the	O
+range	O
+of	O
+herbivores	O
+and	O
+pathogens	O
+that	O
+confront	O
+them	O
+in	O
+the	O
+field	O
+is	O
+the	O
+subject	O
+of	O
+considerable	O
+research	O
+by	O
+both	O
+molecular	O
+biologists	O
+and	O
+ecologists	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+probability	O
+of	O
+cardiopulmonary	O
+complications	O
+increases	O
+significantly	O
+when	O
+patients	O
+develop	O
+class	O
+1	O
+HELLP	O
+syndrome	O
+.	O
+
+The	O
+rate	O
+-	O
+limiting	O
+step	O
+for	O
+telomerase	B-GENE
+activity	O
+seems	O
+to	O
+be	O
+the	O
+expression	O
+of	O
+the	O
+catalytic	O
+subunit	O
+of	O
+the	O
+enzyme	O
+,	O
+encoded	O
+by	O
+the	O
+human	B-GENE
+telomerase	I-GENE
+reverse	I-GENE
+transcriptase	I-GENE
+(	O
+hTERT	B-GENE
+)	O
+gene	O
+.	O
+
+In	O
+the	O
+control	O
+group	O
+,	O
+platelet	O
+markers	O
+increased	O
+1	O
+h	O
+after	O
+surgery	O
+.	O
+
+However	O
+,	O
+the	O
+element	O
+proximal	O
+to	O
+the	O
+transcription	O
+start	O
+site	O
+is	O
+dependent	O
+on	O
+the	O
+SRE	O
+-	O
+1	O
+.	O
+
+Since	O
+proteins	O
+containing	O
+TPR	O
+elements	O
+are	O
+typically	O
+involved	O
+in	O
+multiple	O
+protein	O
+-	O
+protein	O
+interactions	O
+,	O
+we	O
+suggest	O
+that	O
+the	O
+102kD	O
+protein	O
+interacts	O
+within	O
+the	O
+tri	O
+-	O
+snRNP	O
+with	O
+both	O
+the	O
+U5	B-GENE
+and	O
+U4	B-GENE
+/	O
+U6	B-GENE
+snRNPs	O
+,	O
+thus	O
+bridging	O
+the	O
+two	O
+particles	O
+.	O
+
+Antibodies	O
+raised	O
+against	O
+a	O
+C	O
+-	O
+terminal	O
+portion	O
+of	O
+Sec31A	B-GENE
+co	O
+-	O
+precipitate	O
+Sec13	B-GENE
+and	O
+inhibit	O
+ER	O
+-	O
+Golgi	O
+transport	O
+of	O
+temperature	O
+-	O
+arrested	O
+vesicular	O
+stomatitis	B-GENE
+G	I-GENE
+protein	I-GENE
+in	O
+a	O
+semi	O
+-	O
+intact	O
+cell	O
+assay	O
+.	O
+
+Regulation	O
+of	O
+mitochondrial	O
+single	O
+-	O
+stranded	O
+DNA	O
+-	O
+binding	O
+protein	O
+gene	O
+expression	O
+links	O
+nuclear	O
+and	O
+mitochondrial	O
+DNA	O
+replication	O
+in	O
+drosophila	O
+.	O
+
+Genetic	O
+and	O
+molecular	O
+complexity	O
+of	O
+the	O
+position	O
+effect	O
+variegation	O
+modifier	O
+mod	B-GENE
+(	O
+mdg4	B-GENE
+)	O
+in	O
+Drosophila	O
+.	O
+mod	B-GENE
+(	O
+mdg4	B-GENE
+)	O
+,	O
+also	O
+known	O
+as	O
+E	B-GENE
+(	I-GENE
+var	I-GENE
+)	I-GENE
+3	I-GENE
+-	I-GENE
+93D	I-GENE
+,	O
+is	O
+involved	O
+in	O
+a	O
+variety	O
+of	O
+processes	O
+,	O
+such	O
+as	O
+gene	O
+silencing	O
+in	O
+position	O
+effect	O
+variegation	O
+(	O
+PEV	O
+)	O
+,	O
+the	O
+control	O
+of	O
+gypsy	B-GENE
+insulator	I-GENE
+sequences	I-GENE
+,	O
+regulation	O
+of	O
+homeotic	B-GENE
+gene	I-GENE
+expression	O
+,	O
+and	O
+programmed	O
+cell	O
+death	O
+.	O
+
+They	O
+are	O
+present	O
+in	O
+many	O
+kinds	O
+of	O
+living	O
+things	O
+,	O
+but	O
+their	O
+functions	O
+,	O
+especially	O
+those	O
+in	O
+humans	O
+,	O
+are	O
+unclear	O
+.	O
+
+This	O
+tendency	O
+is	O
+likely	O
+due	O
+to	O
+the	O
+biased	O
+nucleotide	O
+composition	O
+of	O
+the	O
+asparagus	O
+genome	O
+,	O
+rather	O
+than	O
+to	O
+the	O
+translational	O
+selection	O
+for	O
+specific	O
+codons	O
+.	O
+
+Transduction	O
+of	O
+the	O
+human	O
+leukemic	O
+cell	O
+line	O
+K562	O
+showed	O
+that	O
+viral	O
+MRP1	B-GENE
+-	O
+PG13	O
+supernatants	O
+routinely	O
+transfer	O
+the	O
+MRP1	B-GENE
+gene	I-GENE
+to	O
+approximately	O
+35	O
+%	O
+of	O
+target	O
+K562	O
+cells	O
+,	O
+of	O
+which	O
+at	O
+least	O
+one	O
+third	O
+are	O
+capable	O
+of	O
+proliferating	O
+in	O
+the	O
+presence	O
+of	O
+otherwise	O
+toxic	O
+concentrations	O
+of	O
+etoposide	O
+.	O
+
+Regulation	O
+of	O
+pituitary	O
+vasopressin	B-GENE
+V1b	I-GENE
+receptors	I-GENE
+plays	O
+a	O
+critical	O
+role	O
+in	O
+regulating	O
+pituitary	B-GENE
+adrenocorticotropic	I-GENE
+hormone	I-GENE
+(	O
+ACTH	B-GENE
+)	O
+secretion	O
+during	O
+adaptation	O
+to	O
+stress	O
+.	O
+
+Identification	O
+of	O
+an	O
+AfsA	B-GENE
+homologue	I-GENE
+(	O
+BarX	B-GENE
+)	O
+from	O
+Streptomyces	O
+virginiae	O
+as	O
+a	O
+pleiotropic	O
+regulator	O
+controlling	O
+autoregulator	O
+biosynthesis	O
+,	O
+virginiamycin	O
+biosynthesis	O
+and	O
+virginiamycin	O
+M1	O
+resistance	O
+.	O
+
+Given	O
+its	O
+relative	O
+longevity	O
+on	O
+the	O
+Web	O
+,	O
+TIE	O
+researchers	O
+have	O
+been	O
+in	O
+a	O
+unique	O
+position	O
+to	O
+observe	O
+trends	O
+in	O
+telemedicine	O
+.	O
+
+Cerebral	O
+vasculitis	O
+secondary	O
+to	O
+Crohn	O
+'	O
+s	O
+disease	O
+seems	O
+to	O
+be	O
+a	O
+very	O
+rare	O
+phenomenon	O
+.	O
+
+To	O
+test	O
+the	O
+hypothesis	O
+that	O
+progestin	O
+-	O
+mediated	O
+increases	O
+in	O
+resting	O
+core	O
+temperature	O
+and	O
+the	O
+core	O
+temperature	O
+threshold	O
+for	O
+sweating	O
+onset	O
+are	O
+counteracted	O
+by	O
+estrogen	O
+,	O
+we	O
+studied	O
+eight	O
+women	O
+(	O
+24	O
++	O
+/	O
+-	O
+2	O
+yr	O
+)	O
+at	O
+27	O
+degrees	O
+C	O
+rest	O
+,	O
+during	O
+20	O
+min	O
+of	O
+passive	O
+heating	O
+(	O
+35	O
+degrees	O
+C	O
+)	O
+,	O
+and	O
+during	O
+40	O
+min	O
+of	O
+exercise	O
+at	O
+35	O
+degrees	O
+C	O
+.	O
+
+Our	O
+data	O
+show	O
+also	O
+that	O
+phagocytic	O
+killing	O
+of	O
+meningococci	O
+is	O
+probably	O
+a	O
+more	O
+consistent	O
+assay	O
+than	O
+antibody	O
+titer	O
+levels	O
+for	O
+antimeningococcal	O
+immunity	O
+,	O
+especially	O
+in	O
+LCC	O
+-	O
+deficient	O
+patients	O
+.	O
+
+These	O
+studies	O
+suggest	O
+an	O
+additional	O
+component	O
+or	O
+cellular	O
+environment	O
+is	O
+required	O
+for	O
+SPRK	B-GENE
+activation	O
+by	O
+Cdc42	B-GENE
+.	O
+
+M	O
+.	O
+
+Jkappa	B-GENE
+DNA	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+were	O
+not	O
+required	O
+for	O
+this	O
+activation	O
+,	O
+and	O
+a	O
+mutant	B-GENE
+EBNA	I-GENE
+-	I-GENE
+3C	I-GENE
+protein	I-GENE
+unable	O
+to	O
+bind	O
+Jkappa	B-GENE
+activated	O
+transcription	O
+as	O
+efficiently	O
+as	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+EBNA	I-GENE
+-	I-GENE
+3C	I-GENE
+,	O
+indicating	O
+that	O
+EBNA	B-GENE
+-	I-GENE
+3C	I-GENE
+can	O
+regulate	O
+transcription	O
+through	O
+a	O
+mechanism	O
+that	O
+is	O
+independent	O
+of	O
+Jkappa	B-GENE
+.	O
+
+Thus	O
+,	O
+both	O
+YY1	B-GENE
+and	O
+CDP	B-GENE
+appear	O
+to	O
+be	O
+negative	O
+regulators	O
+of	O
+the	O
+differentiation	O
+-	O
+induced	O
+HPV	B-GENE
+-	I-GENE
+6	I-GENE
+E1	I-GENE
+promoter	I-GENE
+and	O
+thereby	O
+the	O
+HPV	O
+life	O
+cycle	O
+.	O
+
+Sequential	O
+cleavage	O
+by	O
+metallopeptidases	B-GENE
+and	O
+proteasomes	O
+is	O
+involved	O
+in	O
+processing	O
+HIV	B-GENE
+-	I-GENE
+1	I-GENE
+ENV	I-GENE
+epitope	I-GENE
+for	O
+endogenous	O
+MHC	B-GENE
+class	I-GENE
+I	I-GENE
+antigen	I-GENE
+presentation	O
+.	O
+
+Cloning	O
+and	O
+characterization	O
+of	O
+human	B-GENE
+Lnk	I-GENE
+,	O
+an	O
+adaptor	O
+protein	O
+with	O
+pleckstrin	B-GENE
+homology	O
+and	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+domains	I-GENE
+that	O
+can	O
+inhibit	O
+T	O
+cell	O
+activation	O
+.	O
+
+Vancomycin	O
+data	O
+were	O
+analyzed	O
+according	O
+to	O
+a	O
+one	O
+-	O
+compartment	O
+open	O
+model	O
+with	O
+use	O
+of	O
+NONMEM	O
+population	O
+pharmacokinetic	O
+software	O
+.	O
+
+Finally	O
+,	O
+Cas	B-GENE
+existed	O
+mainly	O
+in	O
+cytosol	O
+and	O
+membrane	O
+cytoskeleton	O
+fractions	O
+in	O
+the	O
+resting	O
+state	O
+,	O
+and	O
+remained	O
+unchanged	O
+during	O
+platelet	O
+aggregation	O
+,	O
+when	O
+FAK	B-GENE
+translocated	O
+to	O
+the	O
+cytoskeletal	O
+fraction	O
+.	O
+
+Transcriptional	O
+regulation	O
+of	O
+the	O
+yeast	B-GENE
+PHO8	I-GENE
+promoter	I-GENE
+in	O
+comparison	O
+to	O
+the	O
+coregulated	O
+PHO5	B-GENE
+promoter	I-GENE
+.	O
+
+The	O
+Siglecs	B-GENE
+are	O
+a	O
+subfamily	O
+of	O
+I	B-GENE
+-	I-GENE
+type	I-GENE
+lectins	I-GENE
+(	O
+immunoglobulin	B-GENE
+superfamily	I-GENE
+proteins	I-GENE
+that	O
+bind	O
+sugars	O
+)	O
+that	O
+specifically	O
+recognize	O
+sialic	O
+acids	O
+.	O
+
+Our	O
+data	O
+provide	O
+a	O
+biochemical	O
+explanation	O
+for	O
+the	O
+similarity	O
+in	O
+phenotype	O
+between	O
+A	O
+-	O
+T	O
+and	O
+NBS	O
+.	O
+
+PATIENTS	O
+OR	O
+OTHER	O
+PARTICIPANTS	O
+:	O
+Twenty	O
+children	O
+met	O
+the	O
+criteria	O
+for	O
+being	O
+learning	O
+disabled	O
+.	O
+
+Update	O
+on	O
+maternal	O
+-	O
+fetal	O
+infections	O
+by	O
+hepatitis	O
+C	O
+,	O
+HIV	O
+and	O
+cytomegalovirus	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+characterized	O
+cis	O
+-	O
+elements	O
+of	O
+the	O
+human	B-GENE
+PCI	I-GENE
+gene	I-GENE
+required	O
+for	O
+expression	O
+in	O
+the	O
+hepatoma	O
+-	O
+derived	O
+cell	O
+line	O
+,	O
+HepG2	O
+cells	O
+,	O
+and	O
+also	O
+evaluated	O
+rat	B-GENE
+PCI	I-GENE
+mRNA	I-GENE
+expression	O
+,	O
+particularly	O
+on	O
+the	O
+effect	O
+of	O
+androgen	O
+in	O
+rat	O
+reproductive	O
+tissues	O
+.	O
+
+In	O
+the	O
+study	O
+on	O
+PCI	B-GENE
+mRNA	I-GENE
+expression	O
+in	O
+the	O
+reproductive	O
+organs	O
+,	O
+we	O
+first	O
+cloned	O
+rat	B-GENE
+PCI	I-GENE
+cDNA	I-GENE
+and	O
+then	O
+evaluated	O
+the	O
+effect	O
+of	O
+androgen	O
+on	O
+the	O
+PCI	B-GENE
+mRNA	I-GENE
+expression	O
+.	O
+
+The	O
+stoichiometry	O
+of	O
+the	O
+complexes	O
+formed	O
+with	O
+the	O
+dodeca	O
+-	O
+satellite	O
+C	O
+strand	O
+suggests	O
+that	O
+,	O
+in	O
+DDP1	B-GENE
+,	O
+the	O
+15	O
+consecutive	O
+KH	O
+domains	O
+are	O
+organized	O
+such	O
+that	O
+they	O
+define	O
+two	O
+nucleic	O
+acid	O
+binding	O
+surfaces	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+mammalian	B-GENE
+translation	I-GENE
+initiation	I-GENE
+factor	I-GENE
+5	I-GENE
+(	O
+eIF5	B-GENE
+)	O
+:	O
+role	O
+of	O
+interaction	O
+between	O
+the	O
+beta	O
+subunit	O
+of	O
+eIF2	B-GENE
+and	O
+eIF5	B-GENE
+in	O
+eIF5	B-GENE
+function	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+Much	O
+evidence	O
+indicates	O
+that	O
+p38	B-GENE
+is	O
+an	O
+activator	O
+of	O
+MyoD	B-GENE
+:	O
+(	O
+i	O
+)	O
+p38	B-GENE
+kinase	I-GENE
+activity	O
+is	O
+required	O
+for	O
+the	O
+expression	O
+of	O
+MyoD	B-GENE
+-	O
+responsive	O
+genes	O
+,	O
+(	O
+ii	O
+)	O
+enforced	O
+induction	O
+of	O
+p38	B-GENE
+stimulates	O
+the	O
+transcriptional	O
+activity	O
+of	O
+a	O
+Gal4	B-GENE
+-	O
+MyoD	B-GENE
+fusion	O
+protein	O
+and	O
+allows	O
+efficient	O
+activation	O
+of	O
+chromatin	O
+-	O
+integrated	O
+reporters	O
+by	O
+MyoD	B-GENE
+,	O
+and	O
+(	O
+iii	O
+)	O
+MyoD	B-GENE
+-	O
+dependent	O
+myogenic	O
+conversion	O
+is	O
+reduced	O
+in	O
+mouse	O
+embryonic	O
+fibroblasts	O
+derived	O
+from	O
+p38alpha	B-GENE
+(	I-GENE
+-	I-GENE
+/	I-GENE
+-	I-GENE
+)	I-GENE
+embryos	O
+.	O
+
+This	O
+activity	O
+is	O
+stimulated	O
+by	O
+complex	O
+formation	O
+with	O
+the	O
+other	O
+eIF2B	B-GENE
+subunits	I-GENE
+.	O
+
+Our	O
+analysis	O
+of	O
+nonsense	O
+mutations	O
+indicates	O
+that	O
+the	O
+C	O
+terminus	O
+of	O
+eIF2Bepsilon	B-GENE
+(	I-GENE
+residues	I-GENE
+518	I-GENE
+to	I-GENE
+712	I-GENE
+)	I-GENE
+is	O
+required	O
+for	O
+both	O
+catalytic	O
+activity	O
+and	O
+interaction	O
+with	O
+eIF2	B-GENE
+.	O
+
+In	O
+contrast	O
+,	O
+mutations	O
+affecting	O
+the	O
+other	O
+two	O
+Nim1p	B-GENE
+-	I-GENE
+related	I-GENE
+kinases	I-GENE
+in	O
+S	O
+.	O
+cerevisiae	O
+,	O
+Hsl1p	B-GENE
+and	O
+Kcc4p	B-GENE
+,	O
+produce	O
+no	O
+detectable	O
+effect	O
+on	O
+septin	B-GENE
+organization	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Physiologic	O
+pacing	O
+provides	O
+little	O
+benefit	O
+over	O
+ventricular	O
+pacing	O
+for	O
+the	O
+prevention	O
+of	O
+stroke	O
+or	O
+death	O
+due	O
+to	O
+cardiovascular	O
+causes	O
+.	O
+
+Among	O
+non	O
+-	O
+cirrhotics	O
+,	O
+lack	O
+of	O
+portal	O
+vein	O
+visualisation	O
+had	O
+a	O
+90	O
+%	O
+sensitivity	O
+,	O
+88	O
+%	O
+specificity	O
+,	O
+94	O
+%	O
+negative	O
+predictive	O
+value	O
+,	O
+and	O
+83	O
+%	O
+positive	O
+predictive	O
+value	O
+in	O
+the	O
+diagnosis	O
+of	O
+pre	O
+-	O
+sinusoidal	O
+portal	O
+hypertension	O
+.	O
+
+The	O
+serine	B-GENE
+-	I-GENE
+threonine	I-GENE
+kinase	I-GENE
+gene	I-GENE
+is	O
+likely	O
+functional	O
+,	O
+whereas	O
+the	O
+zinc	O
+finger	O
+motif	O
+is	O
+likely	O
+nonfunctional	O
+.	O
+
+Stat	B-GENE
+activation	O
+in	O
+response	O
+to	O
+GH	B-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+was	O
+determined	O
+by	O
+reporter	O
+gene	O
+induction	O
+.	O
+
+HFA	O
+134a	O
+had	O
+a	O
+greater	O
+tendency	O
+to	O
+take	O
+up	O
+moisture	O
+from	O
+the	O
+environment	O
+than	O
+did	O
+HFA	O
+227	O
+.	O
+
+RESULTS	O
+:	O
+Abnormal	O
+color	O
+perception	O
+was	O
+found	O
+in	O
+32	O
+%	O
+of	O
+the	O
+epilepsy	O
+patients	O
+treated	O
+with	O
+vigabatrin	O
+monotherapy	O
+and	O
+28	O
+%	O
+of	O
+the	O
+epilepsy	O
+patients	O
+treated	O
+with	O
+carbamazepine	O
+monotherapy	O
+.	O
+
+In	O
+the	O
+SPP2	O
+screening	O
+test	O
+,	O
+a	O
+few	O
+plates	O
+were	O
+not	O
+seen	O
+in	O
+both	O
+groups	O
+.	O
+
+Mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinase	I-GENE
+phosphatase	I-GENE
+-	I-GENE
+3	I-GENE
+(	O
+MKP	B-GENE
+-	I-GENE
+3	I-GENE
+)	O
+is	O
+a	O
+dual	O
+specificity	O
+phosphatase	O
+that	O
+inactivates	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+(	O
+ERK	B-GENE
+)	O
+MAP	B-GENE
+kinases	I-GENE
+.	O
+
+Consistent	O
+with	O
+this	O
+,	O
+we	O
+show	O
+that	O
+peptides	O
+representing	O
+docking	O
+sites	O
+within	O
+the	O
+target	O
+substrates	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+p90	B-GENE
+(	O
+rsk	B-GENE
+)	O
+inhibit	O
+ERK	B-GENE
+-	O
+dependent	O
+activation	O
+of	O
+MKP	B-GENE
+-	I-GENE
+3	I-GENE
+.	O
+
+HPLC	O
+phosphopeptide	O
+mapping	O
+,	O
+amino	O
+acid	O
+sequencing	O
+,	O
+and	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+determined	O
+that	O
+NCLK	B-GENE
+phosphorylates	O
+Ser	O
+(	O
+67	O
+)	O
+of	O
+I	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+When	O
+the	O
+entire	O
+diet	O
+consisted	O
+of	O
+SBF	O
+,	O
+voluntary	O
+feed	O
+intake	O
+was	O
+reduced	O
+,	O
+indicating	O
+that	O
+SBF	O
+should	O
+not	O
+be	O
+fed	O
+to	O
+ponies	O
+as	O
+the	O
+sole	O
+dietary	O
+ingredient	O
+.	O
+
+Hepatitis	O
+C	O
+virus	O
+infection	O
+and	O
+lymphoproliferative	O
+diseases	O
+in	O
+France	O
+:	O
+a	O
+national	O
+study	O
+.	O
+
+Interestingly	O
+,	O
+a	O
+decreased	O
+transcription	O
+from	O
+the	O
+endogenous	O
+c	B-GENE
+-	I-GENE
+Myb	I-GENE
+promoter	I-GENE
+was	O
+observed	O
+in	O
+several	O
+HTLV	O
+-	O
+I	O
+transformed	O
+T	O
+-	O
+cell	O
+lines	O
+.	O
+
+H19	B-GENE
+and	O
+Igf2	B-GENE
+monoallelic	O
+expression	O
+is	O
+regulated	O
+in	O
+two	O
+distinct	O
+ways	O
+by	O
+a	O
+shared	O
+cis	O
+acting	O
+regulatory	O
+region	O
+upstream	O
+of	O
+H19	B-GENE
+.	O
+
+C	O
+.	O
+elegans	O
+KLP	B-GENE
+-	I-GENE
+11	I-GENE
+/	O
+OSM	B-GENE
+-	I-GENE
+3	I-GENE
+/	O
+KAP	B-GENE
+-	I-GENE
+1	I-GENE
+:	O
+orthologs	O
+of	O
+the	O
+sea	B-GENE
+urchin	I-GENE
+kinesin	I-GENE
+-	I-GENE
+II	I-GENE
+,	O
+and	O
+mouse	O
+KIF3A	B-GENE
+/	O
+KIFB	B-GENE
+/	O
+KAP3	B-GENE
+kinesin	B-GENE
+complexes	O
+.	O
+
+BACKGROUND	O
+:	O
+Hepatic	O
+encephalopathy	O
+is	O
+a	O
+neuropsychiatric	O
+syndrome	O
+associated	O
+with	O
+acute	O
+liver	O
+failure	O
+,	O
+chronic	O
+parenchymal	O
+liver	O
+disease	O
+or	O
+portal	O
+systemic	O
+anastomosis	O
+.	O
+
+These	O
+natural	O
+antisense	O
+S	B-GENE
+transcripts	I-GENE
+co	O
+-	O
+exist	O
+with	O
+several	O
+less	O
+abundant	O
+sense	O
+S	B-GENE
+transcripts	I-GENE
+.	O
+
+Nor	O
+is	O
+such	O
+adjustment	O
+possible	O
+unless	O
+one	O
+posits	O
+a	O
+model	O
+that	O
+relates	O
+the	O
+missing	O
+observations	O
+to	O
+other	O
+observed	O
+information	O
+for	O
+each	O
+subject	O
+-	O
+models	O
+that	O
+are	O
+inherently	O
+untestable	O
+.	O
+
+However	O
+,	O
+the	O
+presence	O
+of	O
+effacement	O
+seems	O
+to	O
+be	O
+a	O
+more	O
+reliable	O
+and	O
+practical	O
+parameter	O
+that	O
+will	O
+be	O
+preferred	O
+in	O
+that	O
+prediction	O
+.	O
+
+The	O
+data	O
+are	O
+compatible	O
+with	O
+the	O
+idea	O
+that	O
+YLL031c	B-GENE
+transfers	O
+the	O
+ethanolaminephosphate	O
+to	O
+the	O
+inner	O
+alpha1	O
+-	O
+2	O
+-	O
+linked	O
+mannose	O
+,	O
+i	O
+.	O
+e	O
+.	O
+the	O
+group	O
+that	O
+links	O
+the	O
+GPI	O
+lipid	O
+anchor	O
+to	O
+proteins	O
+,	O
+whereas	O
+Mcd4p	B-GENE
+and	O
+Gpi7p	B-GENE
+transfer	O
+ethanolaminephosphate	O
+onto	O
+the	O
+alpha1	O
+-	O
+4	O
+-	O
+and	O
+alpha1	O
+-	O
+6	O
+-	O
+linked	O
+mannoses	O
+of	O
+the	O
+GPI	O
+anchor	O
+,	O
+respectively	O
+.	O
+
+The	O
+C	O
+terminus	O
+of	O
+TRBP	B-GENE
+binds	O
+to	O
+CBP	B-GENE
+/	O
+p300	B-GENE
+and	O
+DRIP130	B-GENE
+,	O
+a	O
+component	O
+of	O
+the	O
+DRIP	B-GENE
+/	O
+TRAP	B-GENE
+/	O
+ARC	B-GENE
+complex	O
+,	O
+which	O
+suggests	O
+that	O
+TRBP	B-GENE
+may	O
+activate	O
+transcription	O
+by	O
+means	O
+of	O
+such	O
+interactions	O
+.	O
+
+The	O
+patients	O
+who	O
+presented	O
+with	O
+mucocutaneous	O
+disease	O
+also	O
+had	O
+low	O
+CD4	B-GENE
++	I-GENE
+T	O
+lymphocyte	O
+counts	O
+,	O
+and	O
+most	O
+of	O
+them	O
+had	O
+AIDS	O
+defining	O
+illnesses	O
+.	O
+
+Increased	O
+dietary	O
+energy	O
+decreased	O
+PAB	O
+and	O
+the	O
+use	O
+of	O
+added	O
+dietary	O
+CO	O
+rather	O
+than	O
+PF	O
+decreased	O
+PSHL	O
+in	O
+broiler	O
+breeders	O
+between	O
+26	O
+and	O
+47	O
+wk	O
+of	O
+age	O
+.	O
+
+The	O
+gene	O
+amplification	O
+model	O
+of	O
+Coquelle	O
+et	O
+al	O
+.	O
+
+Hierarchy	O
+of	O
+protein	B-GENE
+tyrosine	I-GENE
+kinases	I-GENE
+in	O
+interleukin	B-GENE
+-	I-GENE
+2	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+signaling	O
+:	O
+activation	O
+of	O
+syk	B-GENE
+depends	O
+on	O
+Jak3	B-GENE
+;	O
+however	O
+,	O
+neither	O
+Syk	B-GENE
+nor	O
+Lck	B-GENE
+is	O
+required	O
+for	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+-	O
+mediated	O
+STAT	B-GENE
+activation	O
+.	O
+
+Immobilized	O
+dimers	O
+of	O
+N	B-GENE
+-	I-GENE
+cadherin	I-GENE
+-	O
+Fc	B-GENE
+chimera	O
+mimic	O
+cadherin	O
+-	O
+mediated	O
+cell	O
+contact	O
+formation	O
+:	O
+contribution	O
+of	O
+both	O
+outside	O
+-	O
+in	O
+and	O
+inside	O
+-	O
+out	O
+signals	O
+.	O
+
+The	O
+monoclonal	O
+immunoglobulin	B-GENE
+products	O
+of	O
+plasma	O
+cell	O
+neoplasm	O
+can	O
+give	O
+rise	O
+to	O
+a	O
+variety	O
+of	O
+manifestations	O
+including	O
+hyperviscosity	O
+,	O
+amyloidosis	O
+,	O
+cryoglobulinemia	O
+,	O
+neuropathy	O
+,	O
+and	O
+renal	O
+failure	O
+.	O
+
+Investigation	O
+of	O
+the	O
+structural	O
+basis	O
+of	O
+the	O
+interaction	O
+between	O
+human	B-GENE
+Igs	I-GENE
+and	O
+gp120	B-GENE
+shows	O
+that	O
+the	O
+viral	B-GENE
+gp120	I-GENE
+SAg	I-GENE
+can	O
+interact	O
+only	O
+with	O
+a	O
+subset	O
+of	O
+human	B-GENE
+V	I-GENE
+(	I-GENE
+H	I-GENE
+)	I-GENE
+3	I-GENE
++	I-GENE
+Igs	I-GENE
+.	O
+
+Double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+trial	O
+.	O
+
+Here	O
+,	O
+it	O
+is	O
+shown	O
+that	O
+TAFII250	B-GENE
+,	O
+the	O
+largest	O
+subunit	O
+of	O
+TFIID	B-GENE
+,	O
+contains	O
+two	O
+tandem	O
+bromodomain	O
+modules	O
+that	O
+bind	O
+selectively	O
+to	O
+multiply	O
+acetylated	O
+histone	B-GENE
+H4	I-GENE
+peptides	I-GENE
+.	O
+
+Endostatin	O
+treatment	O
+for	O
+10	O
+minutes	O
+or	O
+24	O
+hours	O
+induced	O
+tyrosine	O
+phosphorylation	O
+of	O
+Shb	B-GENE
+and	O
+formation	O
+of	O
+multiprotein	O
+complexes	O
+.	O
+
+The	O
+transcript	O
+was	O
+initially	O
+identified	O
+as	O
+a	O
+partial	O
+cDNA	O
+sequence	O
+in	O
+the	O
+course	O
+of	O
+constructing	O
+a	O
+transcript	O
+map	O
+of	O
+the	O
+region	O
+between	O
+markers	O
+D11S1765	B-GENE
+and	O
+uteroglobin	B-GENE
+known	O
+to	O
+encompass	O
+the	O
+gene	O
+causing	O
+Best	O
+disease	O
+.	O
+
+The	O
+real	O
+challenge	O
+for	O
+the	O
+future	O
+will	O
+be	O
+the	O
+management	O
+of	O
+patients	O
+who	O
+do	O
+not	O
+respond	O
+to	O
+first	O
+-	O
+line	O
+treatment	O
+.	O
+
+Iodine	O
+deficiency	O
+disorders	O
+in	O
+Bangladesh	O
+.	O
+
+RESULTS	O
+:	O
+Soluble	O
+CD23	B-GENE
+levels	O
+were	O
+significantly	O
+higher	O
+in	O
+women	O
+with	O
+endometriosis	O
+before	O
+treatment	O
+than	O
+in	O
+ten	O
+normal	O
+controls	O
+.	O
+
+CONCLUSION	O
+:	O
+Our	O
+findings	O
+suggest	O
+that	O
+endometriosis	O
+increases	O
+soluble	O
+CD23	B-GENE
+levels	O
+,	O
+which	O
+can	O
+be	O
+suppressed	O
+with	O
+either	O
+danazol	O
+or	O
+leuprolide	O
+acetate	O
+injection	O
+.	O
+
+To	O
+isolate	O
+this	O
+gene	O
+,	O
+a	O
+P	O
+-	O
+1	O
+artificial	O
+chromosome	O
+(	O
+PAC	O
+)	O
+library	O
+was	O
+screened	O
+with	O
+a	O
+full	B-GENE
+length	I-GENE
+UGT2B7	I-GENE
+probe	O
+and	O
+a	O
+clone	O
+of	O
+approximately	O
+100	O
+kb	O
+in	O
+length	O
+was	O
+isolated	O
+.	O
+
+Age	O
+>	O
+/	O
+=	O
+50	O
+years	O
+(	O
+odds	O
+ratio	O
+[	O
+OR	O
+]	O
+,	O
+14	O
+.	O
+1	O
+)	O
+,	O
+BMI	O
+>	O
+/	O
+=	O
+28	O
+kg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+(	O
+OR	O
+,	O
+5	O
+.	O
+7	O
+)	O
+,	O
+triglycerides	O
+>	O
+/	O
+=	O
+1	O
+.	O
+7	O
+mmol	O
+/	O
+L	O
+(	O
+OR	O
+,	O
+5	O
+)	O
+,	O
+and	O
+alanine	B-GENE
+aminotransferase	I-GENE
+(	O
+ALT	B-GENE
+)	O
+>	O
+/	O
+=	O
+2N	O
+(	O
+OR	O
+,	O
+4	O
+.	O
+6	O
+)	O
+were	O
+independently	O
+associated	O
+with	O
+septal	O
+fibrosis	O
+.	O
+
+However	O
+,	O
+the	O
+elderly	O
+group	O
+showed	O
+significantly	O
+longer	O
+mean	O
+residence	O
+times	O
+(	O
+MRTs	O
+)	O
+and	O
+lower	O
+plasma	O
+clearance	O
+of	O
+lidocaine	O
+during	O
+the	O
+period	O
+compared	O
+with	O
+the	O
+adult	O
+group	O
+(	O
+P	O
+<	O
+.	O
+05	O
+)	O
+.	O
+
+Here	O
+,	O
+we	O
+show	O
+that	O
+the	O
+zinc	B-GENE
+finger	I-GENE
+protein	I-GENE
+Gis1	I-GENE
+acts	O
+as	O
+a	O
+dosage	O
+-	O
+dependent	O
+suppressor	O
+of	O
+the	O
+rim15Delta	B-GENE
+defect	O
+in	O
+nutrient	O
+limitation	O
+-	O
+induced	O
+transcriptional	O
+derepression	O
+of	O
+SSA3	B-GENE
+.	O
+
+The	O
+so	O
+-	O
+called	O
+"	B-GENE
+SH3	I-GENE
+"	I-GENE
+segment	I-GENE
+of	O
+the	O
+linker	O
+domain	O
+,	O
+in	O
+contrast	O
+,	O
+shows	O
+species	O
+-	O
+specific	O
+sequence	O
+identity	O
+in	O
+all	O
+but	O
+one	O
+amino	O
+acid	O
+residues	O
+in	O
+both	O
+factors	O
+,	O
+in	O
+cattle	O
+,	O
+human	O
+,	O
+and	O
+mouse	O
+.	O
+
+No	O
+differences	O
+in	O
+total	O
+cholesterol	O
+levels	O
+were	O
+observed	O
+between	O
+mapuches	O
+and	O
+aymaras	O
+.	O
+
+Up	O
+to	O
+95	O
+%	O
+of	O
+the	O
+total	O
+UV	O
+exposure	O
+received	O
+is	O
+in	O
+the	O
+UV	O
+-	O
+A	O
+waveband	O
+(	O
+320	O
+-	O
+400	O
+nm	O
+)	O
+.	O
+
+To	O
+begin	O
+to	O
+characterize	O
+the	O
+role	O
+of	O
+the	O
+RNA	O
+subunits	O
+in	O
+enzyme	O
+function	O
+and	O
+substrate	O
+specificity	O
+,	O
+we	O
+swapped	O
+two	O
+hairpin	O
+structures	O
+(	O
+MRP3	O
+and	O
+P3	O
+)	O
+between	O
+RNase	B-GENE
+MRP	I-GENE
+RNA	I-GENE
+and	O
+RNase	B-GENE
+P	I-GENE
+RNA	I-GENE
+of	I-GENE
+S	I-GENE
+.	I-GENE
+cerevisiae	I-GENE
+.	O
+
+Among	O
+genes	O
+induced	O
+by	O
+added	O
+pMesogenin1	B-GENE
+is	O
+Xwnt	B-GENE
+-	I-GENE
+8	I-GENE
+,	O
+a	O
+signaling	O
+factor	O
+that	O
+induces	O
+a	O
+similar	O
+repertoire	O
+of	O
+marker	O
+genes	O
+and	O
+a	O
+similar	O
+cellular	O
+phenotype	O
+.	O
+
+Accordingly	O
+,	O
+no	O
+Ha	B-GENE
+-	I-GENE
+ras	I-GENE
+codon	I-GENE
+12	I-GENE
+mutations	O
+are	O
+found	O
+in	O
+the	O
+EtNU	O
+-	O
+induced	O
+mammary	O
+tumors	O
+.	O
+
+False	O
+positive	O
+PET	O
+FDG	O
+corresponded	O
+to	O
+lung	O
+infection	O
+,	O
+degenerative	O
+bone	O
+disease	O
+,	O
+and	O
+reconstruction	O
+artifact	O
+.	O
+
+Tumor	O
+stages	O
+were	O
+IIB	O
+(	O
+T3	O
+N0	O
+)	O
+in	O
+52	O
+%	O
+,	O
+IIIA	O
+in	O
+15	O
+%	O
+,	O
+and	O
+IIIB	O
+in	O
+27	O
+%	O
+of	O
+patients	O
+.	O
+
+Similarly	O
+,	O
+comparison	O
+of	O
+percentage	O
+reductions	O
+of	O
+heart	O
+rate	O
+at	O
+supine	O
+,	O
+sitting	O
+and	O
+exercise	O
+by	O
+repeated	O
+measure	O
+analysis	O
+showed	O
+the	O
+Malays	O
+to	O
+have	O
+significantly	O
+higher	O
+change	O
+compared	O
+to	O
+the	O
+Chinese	O
+(	O
+p	O
+=	O
+0	O
+.	O
+040	O
+)	O
+.	O
+
+Consistent	O
+with	O
+our	O
+model	O
+,	O
+CTCF	B-GENE
+binding	O
+is	O
+abolished	O
+by	O
+DNA	O
+methylation	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+determine	O
+the	O
+efficacy	O
+and	O
+safety	O
+of	O
+amphotericin	O
+B	O
+oral	O
+suspension	O
+(	O
+ABOS	O
+)	O
+for	O
+the	O
+treatment	O
+of	O
+fluconazole	O
+refractory	O
+oral	O
+candidiasis	O
+in	O
+persons	O
+with	O
+HIV	O
+infection	O
+.	O
+
+The	O
+experimentally	O
+mapped	O
+regions	O
+of	O
+RPB5	B-GENE
+involved	O
+in	O
+these	O
+interactions	O
+correspond	O
+to	O
+distinct	O
+and	O
+surface	O
+-	O
+exposed	O
+alpha	O
+-	O
+helical	O
+structures	O
+.	O
+
+The	O
+model	O
+indicates	O
+that	O
+a	O
+0	O
+.	O
+076	O
+%	O
+reduction	O
+in	O
+cigarette	O
+consumption	O
+is	O
+associated	O
+with	O
+the	O
+availability	O
+of	O
+nicotine	O
+patches	O
+after	O
+1992	O
+.	O
+
+Paper	O
+alert	O
+.	O
+
+The	O
+tryptase	B-GENE
+locus	I-GENE
+also	O
+contains	O
+at	O
+least	O
+four	O
+tryptase	B-GENE
+-	I-GENE
+like	I-GENE
+pseudogenes	I-GENE
+,	O
+including	O
+mastin	B-GENE
+,	O
+a	O
+gene	O
+expressed	O
+in	O
+dogs	O
+but	O
+not	O
+in	O
+humans	O
+.	O
+
+The	O
+cellular	O
+part	O
+of	O
+the	O
+third	O
+chimeric	O
+clone	O
+shows	O
+significant	O
+homology	O
+to	O
+an	O
+exon	O
+of	O
+the	O
+human	B-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+1	I-GENE
+gene	I-GENE
+,	O
+although	O
+oriented	O
+in	O
+the	O
+antisense	O
+direction	O
+compared	O
+to	O
+the	O
+adjacent	O
+LTR	O
+.	O
+
+OBJECTIVE	O
+:	O
+This	O
+study	O
+was	O
+conducted	O
+to	O
+assess	O
+the	O
+relative	O
+roles	O
+of	O
+99mTc	O
+-	O
+sestamibi	O
+scintimammography	O
+and	O
+sonography	O
+in	O
+the	O
+evaluation	O
+of	O
+breast	O
+lesions	O
+that	O
+are	O
+indeterminate	O
+or	O
+suspicious	O
+on	O
+mammography	O
+or	O
+clinical	O
+examination	O
+.	O
+
+Mutational	O
+analyses	O
+showed	O
+that	O
+in	O
+-	O
+frame	O
+stop	O
+codons	O
+introduced	O
+into	O
+five	O
+of	O
+seven	O
+RNA	B-GENE
+2	I-GENE
+ORFs	I-GENE
+did	O
+not	O
+affect	O
+accumulation	O
+of	O
+progeny	O
+LIYV	B-GENE
+RNA	I-GENE
+1	I-GENE
+or	O
+RNA	B-GENE
+2	I-GENE
+,	O
+confirming	O
+that	O
+RNA	B-GENE
+2	I-GENE
+does	O
+not	O
+encode	O
+proteins	O
+necessary	O
+for	O
+LIYV	O
+RNA	O
+replication	O
+.	O
+
+Role	O
+of	O
+NH	O
+(	O
+2	O
+)	O
+-	O
+and	O
+COOH	O
+-	O
+terminal	O
+domains	O
+of	O
+the	O
+P	B-GENE
+protein	I-GENE
+of	O
+human	O
+parainfluenza	O
+virus	O
+type	O
+3	O
+in	O
+transcription	O
+and	O
+replication	O
+.	O
+
+Phosphorylation	O
+of	O
+tyrosine	O
+residues	O
+in	O
+the	O
+kinase	O
+domain	O
+and	O
+juxtamembrane	O
+region	O
+regulates	O
+the	O
+biological	O
+and	O
+catalytic	O
+activities	O
+of	O
+Eph	B-GENE
+receptors	I-GENE
+.	O
+
+RESULTS	O
+:	O
+Fournier	O
+'	O
+s	O
+gangrene	O
+occurs	O
+worldwide	O
+.	O
+
+Genomic	O
+DNA	O
+sequencing	O
+in	O
+the	O
+vicinity	O
+of	O
+methylmalonyl	B-GENE
+-	I-GENE
+CoA	I-GENE
+mutase	I-GENE
+gene	I-GENE
+(	O
+mutAB	B-GENE
+)	O
+from	O
+a	O
+rifamycin	O
+SV	O
+-	O
+producing	O
+Amycolatopsis	O
+mediterranei	O
+U32	O
+allowed	O
+us	O
+to	O
+clone	O
+,	O
+sequence	O
+,	O
+and	O
+identify	O
+a	O
+gene	O
+encoding	O
+a	O
+novel	O
+serine	B-GENE
+/	I-GENE
+threonine	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+amk	B-GENE
+)	O
+.	O
+
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+is	O
+accepted	O
+as	O
+a	O
+standard	O
+treatment	O
+used	O
+alone	O
+,	O
+or	O
+in	O
+combination	O
+with	O
+chemotherapy	O
+or	O
+biotherapy	O
+in	O
+the	O
+management	O
+of	O
+metastatic	O
+melanoma	O
+and	O
+metastatic	O
+renal	O
+cell	O
+carcinoma	O
+.	O
+
+Moreover	O
+,	O
+expression	O
+of	O
+antisense	B-GENE
+Ha	I-GENE
+-	I-GENE
+Ras	I-GENE
+or	O
+dominant	B-GENE
+negative	I-GENE
+Raf	I-GENE
+-	I-GENE
+1	I-GENE
+abrogated	O
+the	O
+mitogenic	O
+effect	O
+of	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+in	O
+TSU	O
+-	O
+Pr1	O
+,	O
+and	O
+the	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+inhibition	O
+of	O
+DU145	O
+was	O
+switched	O
+to	O
+stimulation	O
+by	O
+V12Ha	B-GENE
+-	I-GENE
+Ras	I-GENE
+transfection	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+prostate	O
+carcinomas	O
+with	O
+the	O
+Ras	B-GENE
+/	O
+MAPK	B-GENE
+pathway	O
+activation	O
+might	O
+have	O
+a	O
+selective	O
+growth	O
+advantage	O
+by	O
+autocrine	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+production	O
+.	O
+
+Vbeta	B-GENE
+segments	O
+are	O
+appended	O
+to	O
+DJbeta	B-GENE
+rearrangements	O
+,	O
+with	O
+little	O
+or	O
+no	O
+direct	O
+Vbeta	B-GENE
+to	O
+Jbeta	B-GENE
+joining	O
+,	O
+despite	O
+12	O
+/	O
+23	O
+compatibility	O
+of	O
+Vbeta	B-GENE
+23	I-GENE
+-	I-GENE
+RSSs	I-GENE
+and	O
+Jbeta12	B-GENE
+-	I-GENE
+RSSs	I-GENE
+.	O
+
+For	O
+oral	O
+administration	O
+,	O
+AUC0	O
+-	O
+infinity	O
+was	O
+58	O
+.	O
+47	O
++	O
+/	O
+-	O
+16	O
+.	O
+37	O
+microg	O
+x	O
+h	O
+/	O
+ml	O
+,	O
+t1	O
+/	O
+2beta	O
+was	O
+18	O
+.	O
+39	O
++	O
+/	O
+-	O
+0	O
+.	O
+06	O
+hours	O
+,	O
+maximum	O
+concentration	O
+(	O
+Cmax	O
+)	O
+was	O
+2	O
+.	O
+12	O
++	O
+/	O
+-	O
+00	O
+.	O
+51	O
+microg	O
+/	O
+ml	O
+,	O
+time	O
+to	O
+Cmax	O
+was	O
+2	O
+.	O
+20	O
++	O
+/	O
+-	O
+2	O
+.	O
+17	O
+hours	O
+,	O
+mean	O
+absorption	O
+time	O
+was	O
+2	O
+.	O
+09	O
++	O
+/	O
+-	O
+0	O
+.	O
+51	O
+hours	O
+,	O
+and	O
+bioavailability	O
+was	O
+42	O
++	O
+/	O
+-	O
+0	O
+.	O
+42	O
+%	O
+.	O
+
+In	O
+experiment	O
+2	O
+,	O
+no	O
+difference	O
+in	O
+gastric	O
+emptying	O
+of	O
+40	O
+%	O
+peptone	O
+or	O
+25	O
+%	O
+glucose	O
+was	O
+found	O
+between	O
+rats	O
+receiving	O
+TPN	O
+and	O
+those	O
+receiving	O
+intragastric	O
+nutrition	O
+for	O
+10	O
+to	O
+12	O
+days	O
+.	O
+
+In	O
+contrast	O
+,	O
+H	B-GENE
+-	I-GENE
+NS	I-GENE
+negative	O
+regulation	O
+operated	O
+only	O
+in	O
+the	O
+absence	O
+of	O
+Fur	B-GENE
+.	O
+
+Thus	O
+,	O
+SAG	B-GENE
+appears	O
+to	O
+control	O
+cell	O
+cycle	O
+progression	O
+in	O
+yeast	O
+by	O
+promoting	O
+ubiquitination	O
+and	O
+degradation	O
+of	O
+cell	O
+cycle	O
+regulatory	O
+proteins	O
+.	O
+
+It	O
+brings	O
+about	O
+fatigue	O
+,	O
+negative	O
+moods	O
+,	O
+and	O
+impaired	O
+health	O
+,	O
+sleep	O
+,	O
+safety	O
+,	O
+and	O
+working	O
+capacity	O
+.	O
+
+This	O
+demonstrates	O
+that	O
+treatment	O
+of	O
+the	O
+graft	O
+recipient	O
+for	O
+a	O
+relatively	O
+short	O
+period	O
+during	O
+and	O
+after	O
+surgery	O
+has	O
+a	O
+favorable	O
+effect	O
+on	O
+the	O
+survival	O
+of	O
+grafted	O
+dopaminergic	O
+neurons	O
+.	O
+
+The	O
+relationships	O
+among	O
+blood	O
+concentrations	O
+of	O
+thyroid	O
+hormones	O
+and	O
+selenium	O
+,	O
+zinc	O
+,	O
+retinol	O
+,	O
+and	O
+alpha	O
+-	O
+tocopherol	O
+were	O
+studied	O
+in	O
+44	O
+healthy	O
+Northern	O
+Italian	O
+oldest	O
+-	O
+old	O
+subjects	O
+(	O
+age	O
+range	O
+,	O
+90	O
+-	O
+107	O
+yr	O
+)	O
+,	O
+selected	O
+by	O
+the	O
+criteria	O
+of	O
+the	O
+SENIEUR	O
+protocol	O
+.	O
+
+Chinese	O
+Spring	O
+(	O
+CS	O
+)	O
+carrying	O
+the	O
+Q	B-GENE
+gene	I-GENE
+to	O
+those	O
+of	O
+a	O
+chromosome	O
+deletion	O
+line	O
+of	O
+CS	O
+,	O
+namely	O
+,	O
+q5	O
+,	O
+which	O
+lacks	O
+15	O
+%	O
+of	O
+5AL	O
+including	O
+the	O
+Q	B-GENE
+gene	I-GENE
+.	O
+
+Investigations	O
+using	O
+hippocampal	O
+slices	O
+maintained	O
+in	O
+vitro	O
+have	O
+demonstrated	O
+that	O
+bursts	O
+of	O
+oscillatory	O
+field	O
+potentials	O
+in	O
+the	O
+gamma	O
+frequency	O
+range	O
+(	O
+30	O
+-	O
+80	O
+Hz	O
+)	O
+are	O
+followed	O
+by	O
+a	O
+slower	O
+oscillation	O
+in	O
+the	O
+beta	O
+1	O
+range	O
+(	O
+12	O
+-	O
+20	O
+Hz	O
+)	O
+.	O
+
+Karger	O
+AG	O
+,	O
+Basel	O
+
+During	O
+surgery	O
+bone	O
+cysts	O
+were	O
+excised	O
+and	O
+filled	O
+by	O
+bone	O
+grafts	O
+.	O
+
+Urinary	O
+LTE4	O
+increased	O
+after	O
+both	O
+challenges	O
+the	O
+rise	O
+being	O
+higher	O
+following	O
+oral	O
+as	O
+compared	O
+to	O
+inhalation	O
+provocation	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+Basal	O
+FVR	O
+was	O
+reduced	O
+by	O
+approximately	O
+18	O
+%	O
+by	O
+ERT	O
+and	O
+HRT	O
+,	O
+but	O
+FVR	O
+responses	O
+to	O
+noradrenaline	O
+,	O
+angiotensin	B-GENE
+II	I-GENE
+,	O
+acetylcholine	O
+and	O
+nitroprusside	O
+were	O
+unaffected	O
+.	O
+
+Three	O
+FGF	B-GENE
+-	I-GENE
+AS	I-GENE
+cDNAs	I-GENE
+were	O
+isolated	O
+;	O
+the	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+FGF	I-GENE
+-	I-GENE
+AS	I-GENE
+mRNA	I-GENE
+and	O
+two	O
+alternative	O
+splice	O
+variants	O
+lacking	O
+exon	O
+2	O
+or	O
+exons	O
+2	O
+and	O
+3	O
+of	O
+the	O
+FGF	B-GENE
+-	I-GENE
+AS	I-GENE
+sequence	I-GENE
+.	O
+
+Characterization	O
+of	O
+polymorphic	O
+TNRs	O
+in	O
+novel	O
+and	O
+even	O
+known	O
+genes	O
+expressed	O
+in	O
+human	O
+spinal	O
+cord	O
+is	O
+likely	O
+to	O
+help	O
+in	O
+the	O
+identification	O
+of	O
+new	O
+candidates	O
+for	O
+genes	O
+involved	O
+in	O
+neurodegenerative	O
+disorders	O
+.	O
+
+Finally	O
+,	O
+in	O
+situ	O
+RNA	O
+hybridization	O
+studies	O
+revealed	O
+a	O
+very	O
+specific	O
+pattern	O
+of	O
+EphA8	B-GENE
+gene	I-GENE
+expression	O
+restricted	O
+to	O
+the	O
+rostral	O
+region	O
+of	O
+midbrain	O
+tectum	O
+during	O
+embryonic	O
+development	O
+.	O
+
+Transfection	O
+of	O
+cDNAs	O
+for	O
+three	O
+mutant	O
+enzymes	O
+into	O
+FPGS	B-GENE
+-	O
+null	O
+Chinese	O
+hamster	O
+ovary	O
+cells	O
+restored	O
+a	O
+reduced	O
+level	O
+of	O
+clonal	O
+growth	O
+,	O
+whereas	O
+a	O
+T339I	O
+mutant	O
+supported	O
+growth	O
+at	O
+a	O
+level	O
+comparable	O
+to	O
+that	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+enzyme	O
+.	O
+
+SETTING	O
+:	O
+University	O
+of	O
+Paris	O
+VII	O
+hospital	O
+.	O
+Patient	O
+(	O
+s	O
+)	O
+:	O
+Nine	O
+women	O
+had	O
+embolization	O
+for	O
+symptomatic	O
+myoma	O
+,	O
+with	O
+12	O
+pregnancies	O
+observed	O
+.	O
+
+Improving	O
+fissure	O
+sealant	O
+quality	O
+:	O
+mechanical	O
+preparation	O
+and	O
+filling	O
+level	O
+.	O
+
+The	O
+Menopause	O
+-	O
+Rating	O
+-	O
+Scale	O
+(	O
+MRS	O
+I	O
+)	O
+was	O
+used	O
+in	O
+clinical	O
+practice	O
+since	O
+1992	O
+.	O
+
+The	O
+MRS	O
+II	O
+meets	O
+a	O
+high	O
+methodological	O
+standard	O
+as	O
+an	O
+instrument	O
+standardized	O
+in	O
+the	O
+population	O
+.	O
+
+The	O
+protein	O
+encoded	O
+by	O
+the	O
+fruA	B-GENE
+transcript	I-GENE
+is	O
+well	O
+conserved	O
+with	O
+the	O
+D	B-GENE
+.	I-GENE
+melanogaster	I-GENE
+type	I-GENE
+A	I-GENE
+protein	I-GENE
+,	O
+particularly	O
+the	O
+BTB	B-GENE
+protein	I-GENE
+-	O
+protein	O
+-	O
+binding	O
+domain	O
+,	O
+which	O
+is	O
+encoded	O
+by	O
+exons	O
+I	O
+and	O
+II	O
+and	O
+is	O
+100	O
+%	O
+conserved	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+mouse	O
+ortholog	O
+(	O
+Mharp	B-GENE
+/	O
+Smarcal1	B-GENE
+)	O
+was	O
+cloned	O
+,	O
+and	O
+the	O
+Caenorhabditis	O
+elegans	O
+ortholog	O
+(	O
+CEHARP	B-GENE
+)	O
+was	O
+identified	O
+in	O
+the	O
+GenBank	O
+database	O
+.	O
+
+Sparfloxacin	O
+and	O
+clinafloxacin	O
+were	O
+evaluated	O
+against	O
+Enterococcus	O
+faecium	O
+SF2149	O
+and	O
+Enterococcus	O
+faecalis	O
+WH245	O
+,	O
+respectively	O
+.	O
+
+ECP	B-GENE
+and	O
+tryptase	B-GENE
+levels	O
+in	O
+serum	O
+were	O
+measured	O
+before	O
+and	O
+after	O
+the	O
+last	O
+oral	O
+challenge	O
+.	O
+
+Tolterodine	O
+users	O
+were	O
+7	O
+.	O
+5	O
+times	O
+more	O
+likely	O
+to	O
+have	O
+received	O
+another	O
+spasmolytic	O
+drug	O
+(	O
+RR	O
+7	O
+.	O
+5	O
+,	O
+95	O
+%	O
+CI	O
+4	O
+.	O
+8	O
+to	O
+11	O
+.	O
+9	O
+)	O
+.	O
+
+For	O
+an	O
+unsupervised	O
+program	O
+,	O
+the	O
+costs	O
+were	O
+estimated	O
+at	O
+$	O
+311	O
+for	O
+the	O
+first	O
+year	O
+and	O
+$	O
+73	O
+for	O
+all	O
+additional	O
+years	O
+.	O
+
+The	O
+presence	O
+of	O
+such	O
+a	O
+putative	O
+RNA	O
+-	O
+binding	O
+domain	O
+suggests	O
+a	O
+mechanism	O
+for	O
+the	O
+observed	O
+autoregulation	O
+of	O
+bacteriophage	O
+T4	B-GENE
+DNA	I-GENE
+polymerase	I-GENE
+synthesis	O
+by	O
+binding	O
+to	O
+its	O
+own	O
+mRNA	O
+.	O
+
+Deletion	O
+and	O
+mutational	O
+analyses	O
+revealed	O
+two	O
+positive	O
+cis	O
+-	O
+regulatory	O
+elements	O
+in	O
+this	O
+region	O
+that	O
+are	O
+essential	O
+for	O
+CSX1	B-GENE
+expression	O
+in	O
+cardiomyocytes	O
+.	O
+
+Functional	O
+studies	O
+which	O
+introduced	O
+a	O
+mutation	O
+in	O
+the	O
+AP2	B-GENE
+core	I-GENE
+binding	I-GENE
+region	I-GENE
+as	O
+well	O
+as	O
+cotransfection	O
+experiments	O
+using	O
+an	O
+AP2	B-GENE
+expression	O
+vector	O
+revealed	O
+that	O
+AP2	B-GENE
+exerts	O
+a	O
+repressive	O
+role	O
+on	O
+the	O
+HGF	B-GENE
+gene	I-GENE
+promoter	I-GENE
+activity	O
+.	O
+
+In	O
+reconstitution	O
+experiments	O
+,	O
+we	O
+first	O
+showed	O
+that	O
+expression	O
+in	O
+the	O
+RAW	O
+264	O
+.	O
+7	O
+cell	O
+line	O
+of	O
+C	B-GENE
+-	I-GENE
+terminal	I-GENE
+Src	I-GENE
+kinase	I-GENE
+(	O
+Csk	B-GENE
+)	O
+inhibited	O
+and	O
+that	O
+of	O
+a	O
+membrane	O
+-	O
+anchored	O
+,	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+Csk	B-GENE
+abolished	O
+the	O
+Fc	B-GENE
+gamma	I-GENE
+R	I-GENE
+-	O
+mediated	O
+signaling	O
+that	O
+leads	O
+to	O
+phagocytosis	O
+in	O
+a	O
+kinase	O
+-	O
+dependent	O
+manner	O
+.	O
+
+In	O
+contrast	O
+,	O
+c	B-GENE
+-	I-GENE
+Src	I-GENE
+-	I-GENE
+derived	I-GENE
+construct	I-GENE
+(	O
+a	B-GENE
+-	I-GENE
+Src	I-GENE
+)	O
+,	O
+that	O
+was	O
+excluded	O
+from	O
+detergent	O
+-	O
+resistant	O
+membranes	O
+,	O
+could	O
+not	O
+restore	O
+the	O
+series	O
+of	O
+phagocytosis	O
+signaling	O
+.	O
+
+The	O
+pJR	O
+vectors	O
+differ	O
+among	O
+them	O
+in	O
+:	O
+(	O
+a	O
+)	O
+the	O
+selectable	O
+marker	O
+(	O
+Saccharomyces	O
+cerevisiae	O
+LEU	B-GENE
+2	I-GENE
+gene	I-GENE
+,	O
+which	O
+complements	O
+S	B-GENE
+.	I-GENE
+pombe	I-GENE
+leu1	I-GENE
+-	I-GENE
+gene	I-GENE
+and	O
+S	O
+.	O
+pombe	O
+ura4	B-GENE
++	I-GENE
+and	O
+his3	B-GENE
++	I-GENE
+genes	I-GENE
+)	O
+;	O
+(	O
+b	O
+)	O
+the	O
+thiamine	O
+-	O
+repressible	O
+nmt1	B-GENE
+promoter	I-GENE
+(	O
+3X	O
+,	O
+41X	O
+and	O
+81X	O
+with	O
+extremely	O
+high	O
+,	O
+moderate	O
+or	O
+low	O
+transcription	O
+efficiency	O
+,	O
+respectively	O
+)	O
+;	O
+and	O
+(	O
+c	O
+)	O
+the	O
+multiple	O
+cloning	O
+site	O
+(	O
+two	O
+multiple	O
+cloning	O
+sites	O
+,	O
+with	O
+12	O
+restriction	O
+sites	O
+each	O
+)	O
+.	O
+
+(	O
+GUT	O
+)	O
+Sera	O
+of	O
+30	O
+montoux	O
+negative	O
+healthy	O
+adults	O
+(	O
+age	O
+/	O
+sex	O
+matched	O
+)	O
+were	O
+taken	O
+as	O
+control	O
+by	O
+detecting	O
+IgG	B-GENE
+anti	I-GENE
+bodies	I-GENE
+to	O
+A60	B-GENE
+antigen	I-GENE
+.	O
+
+Franz	O
+Schubert	O
+-	O
+-	O
+his	O
+life	O
+,	O
+music	O
+and	O
+diseases	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+N	O
+-	O
+glycans	O
+flanking	O
+the	O
+receptor	O
+-	O
+binding	O
+site	O
+of	O
+the	O
+HA	B-GENE
+molecule	I-GENE
+are	O
+potent	O
+regulators	O
+of	O
+influenza	O
+virus	O
+growth	O
+,	O
+with	O
+the	O
+glycan	O
+at	O
+Asn149	O
+being	O
+dominant	O
+and	O
+that	O
+at	O
+Asn123	O
+being	O
+less	O
+effective	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+introduction	O
+of	O
+the	O
+PAIP	O
+resulted	O
+in	O
+a	O
+significant	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+reduction	O
+in	O
+contaminating	O
+WBCs	O
+(	O
+median	O
+,	O
+30	O
+,	O
+000	O
+)	O
+from	O
+the	O
+numbers	O
+seen	O
+with	O
+FIP	O
+(	O
+median	O
+,	O
+2	O
+,	O
+300	O
+,	O
+000	O
+)	O
+while	O
+maintaining	O
+the	O
+separation	O
+efficacy	O
+(	O
+47	O
+%	O
+)	O
+and	O
+separation	O
+time	O
+.	O
+
+All	O
+were	O
+tested	O
+for	O
+serum	O
+ferritin	B-GENE
+(	O
+SF	B-GENE
+)	O
+,	O
+hemoglobin	B-GENE
+(	O
+Hb	B-GENE
+)	O
+level	O
+and	O
+asked	O
+for	O
+detailed	O
+histories	O
+of	O
+donations	O
+and	O
+iron	O
+supplementation	O
+.	O
+
+Vascular	B-GENE
+endothelial	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+VEGF	B-GENE
+)	O
+,	O
+a	O
+potent	O
+agonist	O
+secreted	O
+by	O
+virtually	O
+all	O
+cells	O
+,	O
+controls	O
+migration	O
+and	O
+division	O
+of	O
+vascular	O
+endothelial	O
+cells	O
+.	O
+
+The	O
+antioxidant	O
+agent	O
+pyrrolidine	O
+dithiocarbamate	O
+(	O
+PDTC	O
+)	O
+has	O
+been	O
+shown	O
+to	O
+protect	O
+endothelial	O
+cells	O
+(	O
+EC	O
+)	O
+from	O
+pro	O
+-	O
+inflammatory	O
+-	O
+induced	O
+and	O
+pro	O
+-	O
+oxidant	O
+-	O
+induced	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activation	O
+.	O
+
+We	O
+further	O
+studied	O
+the	O
+effects	O
+of	O
+SIE	B-GENE
+-	I-GENE
+1	I-GENE
+hypermethylation	O
+on	O
+p21WAF1	B-GENE
+induction	O
+by	O
+STAT	B-GENE
+activation	O
+.	O
+
+In	O
+the	O
+pRb	B-GENE
+(	I-GENE
+-	I-GENE
+)	I-GENE
+SAOS	O
+-	O
+2	O
+cell	O
+line	O
+transiently	O
+transfected	O
+with	O
+a	O
+reporter	O
+plasmid	O
+containing	O
+six	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+binding	I-GENE
+site	I-GENE
+,	O
+pRb	B-GENE
+enhances	O
+the	O
+transcriptional	O
+activity	O
+of	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+E12	B-GENE
+-	O
+Lmo2	B-GENE
+and	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+E12	B-GENE
+-	O
+Lmo2	B-GENE
+-	O
+Ldb1	B-GENE
+complexes	O
+but	O
+not	O
+that	O
+of	O
+a	O
+tal	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+E12	B-GENE
+heterodimer	O
+.	O
+
+This	O
+effect	O
+was	O
+not	O
+seen	O
+in	O
+conjunction	O
+with	O
+oxycodone	O
+,	O
+a	O
+morphine	B-GENE
+-	I-GENE
+like	I-GENE
+mu	I-GENE
+-	I-GENE
+receptor	I-GENE
+agonist	O
+.	O
+
+Neurofibromatosis	O
+of	O
+the	O
+breast	O
+in	O
+a	O
+patient	O
+with	O
+Morbus	O
+von	O
+Recklinghausen	O
+
+In	O
+the	O
+premating	O
+period	O
+male	O
+rate	O
+of	O
+aggression	O
+was	O
+not	O
+significantly	O
+correlated	O
+with	O
+testosterone	O
+level	O
+.	O
+
+These	O
+results	O
+support	O
+the	O
+hypothesis	O
+that	O
+in	O
+the	O
+presence	O
+of	O
+tryptophan	O
+the	O
+ribosome	O
+translating	O
+tnaC	B-GENE
+blocks	O
+Rho	B-GENE
+'	O
+s	O
+access	O
+to	O
+the	O
+boxA	B-GENE
+and	O
+rut	B-GENE
+sites	I-GENE
+,	O
+thereby	O
+preventing	O
+transcription	O
+termination	O
+.	O
+
+In	O
+situ	O
+hybridization	O
+with	O
+the	O
+antisense	O
+RNA	O
+probes	O
+further	O
+supported	O
+the	O
+expression	O
+changes	O
+of	O
+these	O
+six	O
+clones	O
+and	O
+localized	O
+the	O
+changes	O
+in	O
+multiple	O
+germ	O
+cell	O
+stages	O
+as	O
+well	O
+as	O
+other	O
+cell	O
+types	O
+(	O
+Sertoli	O
+,	O
+interstitial	O
+and	O
+peritubular	O
+cells	O
+)	O
+.	O
+
+The	O
+administration	O
+of	O
+the	O
+GnRH	B-GENE
+agonist	O
+reduced	O
+the	O
+bone	O
+mineral	O
+density	O
+in	O
+the	O
+whole	O
+femur	O
+to	O
+91	O
+.	O
+0	O
+%	O
+of	O
+that	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+This	O
+study	O
+shows	O
+that	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+is	O
+the	O
+predominant	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+isoform	I-GENE
+found	O
+in	O
+activated	O
+stellate	O
+cells	O
+and	O
+that	O
+increased	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+protein	I-GENE
+and	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+binding	O
+to	O
+a	O
+proximal	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+binding	I-GENE
+site	I-GENE
+in	O
+the	O
+promoter	O
+mediates	O
+the	O
+activating	O
+effect	O
+of	O
+acetaldehyde	O
+.	O
+
+As	O
+with	O
+VP16	B-GENE
+,	O
+the	O
+transactivation	O
+function	O
+of	O
+Luman	B-GENE
+is	O
+also	O
+regulated	O
+by	O
+HCF	B-GENE
+.	O
+
+After	O
+two	O
+successive	O
+rounds	O
+of	O
+selection	O
+by	O
+focus	O
+formation	O
+assay	O
+,	O
+a	O
+transforming	O
+ribozyme	O
+(	O
+Rz007	B-GENE
+)	O
+was	O
+identified	O
+.	O
+
+G	O
+.	O
+,	O
+and	O
+Hyde	O
+,	O
+C	O
+.	O
+
+The	O
+ATR	O
+-	O
+X	O
+syndrome	O
+results	O
+from	O
+mutations	O
+of	O
+the	O
+XH2	B-GENE
+gene	I-GENE
+,	O
+located	O
+on	O
+the	O
+X	O
+chromosome	O
+(	O
+Xq13	O
+.	O
+3	O
+)	O
+and	O
+coding	O
+for	O
+a	O
+transacting	O
+factor	O
+which	O
+regulates	O
+gene	O
+expression	O
+.	O
+
+AIMS	O
+:	O
+To	O
+evaluate	O
+the	O
+role	O
+of	O
+environmental	O
+intra	O
+-	O
+uterine	O
+factors	O
+in	O
+determining	O
+the	O
+birthweights	O
+of	O
+twins	O
+with	O
+increased	O
+susceptibility	O
+to	O
+diabetes	O
+and	O
+discordant	O
+for	O
+abnormal	O
+responses	O
+to	O
+the	O
+oral	O
+glucose	O
+tolerance	O
+test	O
+(	O
+OGTT	O
+)	O
+and	O
+verify	O
+the	O
+possible	O
+association	O
+of	O
+within	O
+-	O
+pair	O
+birthweight	O
+differences	O
+and	O
+metabolic	O
+abnormalities	O
+in	O
+adult	O
+life	O
+.	O
+
+In	O
+NASCIS	O
+III	O
+,	O
+a	O
+randomization	O
+imbalance	O
+occurred	O
+that	O
+allocated	O
+a	O
+disproportionate	O
+number	O
+of	O
+patients	O
+with	O
+no	O
+motor	O
+deficit	O
+(	O
+and	O
+therefore	O
+no	O
+chance	O
+for	O
+recovery	O
+)	O
+to	O
+the	O
+lower	O
+dose	O
+control	O
+group	O
+.	O
+
+Penicillin	B-GENE
+acylase	I-GENE
+(	O
+PA	B-GENE
+)	O
+from	O
+Escherichia	O
+coli	O
+ATCC11105	O
+is	O
+a	O
+periplasmic	O
+heterodimer	O
+consisting	O
+of	O
+a	O
+24	O
+kDa	O
+small	O
+subunit	O
+and	O
+a	O
+65	O
+kDa	O
+large	O
+subunit	O
+.	O
+
+A	O
+murine	O
+expressed	O
+sequence	O
+tag	O
+(	O
+EST	O
+)	O
+showing	O
+homology	O
+with	O
+erythropoietin	B-GENE
+receptor	I-GENE
+(	O
+EPOR	B-GENE
+)	O
+was	O
+identified	O
+in	O
+the	O
+EST	O
+database	O
+.	O
+
+When	O
+the	O
+LCx	O
+was	O
+partially	O
+occluded	O
+,	O
+mild	O
+PM	O
+-	O
+induced	O
+tachycardia	O
+resulted	O
+in	O
+decreased	O
+AoP	O
+(	O
+P	O
+=	O
+0	O
+.	O
+045	O
+)	O
+as	O
+well	O
+as	O
+in	O
+decreased	O
+SV	O
+(	O
+P	O
+=	O
+0	O
+.	O
+048	O
+)	O
+;	O
+the	O
+LVEDP	O
+remained	O
+high	O
+(	O
+P	O
+=	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+Activation	O
+of	O
+nuclear	B-GENE
+factor	I-GENE
+(	I-GENE
+NF	I-GENE
+)	I-GENE
+-	I-GENE
+kappaB	I-GENE
+and	O
+subsequent	O
+proinflammatory	O
+gene	O
+expression	O
+in	O
+human	O
+airway	O
+epithelial	O
+cells	O
+can	O
+be	O
+evoked	O
+by	O
+oxidative	O
+stress	O
+.	O
+
+GAP	O
+JUNCTIONS	O
+IN	O
+THE	O
+BRAIN	O
+:	O
+PREFACE	O
+.	O
+
+We	O
+have	O
+isolated	O
+and	O
+functionally	O
+characterized	O
+the	O
+mouse	O
+gene	O
+for	O
+the	O
+C2	O
+subunit	O
+of	O
+the	O
+20S	B-GENE
+proteasome	I-GENE
+.	O
+
+Furthermore	O
+,	O
+as	O
+in	O
+the	O
+human	O
+gene	O
+,	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+Cacna1f	B-GENE
+gene	I-GENE
+maps	O
+within	O
+5	O
+kb	O
+of	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+mouse	B-GENE
+synaptophysin	I-GENE
+gene	I-GENE
+in	O
+a	O
+region	O
+orthologous	O
+to	O
+Xp11	O
+.	O
+23	O
+.	O
+
+With	O
+the	O
+human	B-GENE
+Rhotekin	I-GENE
+cDNA	I-GENE
+as	O
+a	O
+probe	O
+,	O
+Northern	O
+hybridization	O
+revealed	O
+that	O
+a	O
+4	O
+.	O
+0	O
+-	O
+kb	O
+transcript	O
+was	O
+expressed	O
+at	O
+a	O
+high	O
+level	O
+in	O
+prostate	O
+and	O
+at	O
+a	O
+middle	O
+level	O
+in	O
+13	O
+of	O
+16	O
+tissues	O
+examined	O
+,	O
+but	O
+it	O
+cannot	O
+be	O
+detected	O
+in	O
+liver	O
+and	O
+lung	O
+tissues	O
+.	O
+
+Similarly	O
+,	O
+co	O
+-	O
+expression	O
+of	O
+a	O
+dominant	O
+-	O
+negative	O
+mutant	O
+of	O
+p38alpha	B-GENE
+,	O
+but	O
+not	O
+of	O
+ERK1	B-GENE
+,	O
+ERK2	B-GENE
+,	O
+JNK1	B-GENE
+,	O
+or	O
+JNK2	B-GENE
+,	O
+reduces	O
+basal	O
+and	O
+cadmium	O
+-	O
+induced	O
+pE1	B-GENE
+-	I-GENE
+luc	I-GENE
+activity	O
+.	O
+
+BACKGROUND	O
+:	O
+Gamma	O
+knife	O
+radiosurgery	O
+(	O
+GKR	O
+)	O
+is	O
+a	O
+safe	O
+and	O
+effective	O
+alternative	O
+to	O
+surgery	O
+for	O
+intracranial	O
+lesions	O
+.	O
+
+It	O
+is	O
+mainly	O
+transcribed	O
+in	O
+neural	O
+structures	O
+and	O
+in	O
+developing	O
+organs	O
+characterized	O
+by	O
+epithelial	O
+-	O
+mesenchymal	O
+interactions	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+alpha2	O
+-	O
+adrenergic	O
+antagonist	O
+idazoxan	O
+increases	O
+glucose	O
+-	O
+induced	O
+sympathetic	O
+activity	O
+but	O
+not	O
+energy	O
+expenditure	O
+in	O
+obese	O
+subjects	O
+.	O
+
+Next	O
+,	O
+we	O
+show	O
+that	O
+two	O
+EMS	O
+-	O
+induced	O
+mutations	O
+,	O
+previously	O
+shown	O
+to	O
+interact	O
+genetically	O
+with	O
+zipper	O
+(	O
+Ebr	B-GENE
+)	O
+,	O
+disrupt	O
+the	O
+RhoA	B-GENE
+locus	I-GENE
+.	O
+
+Therefore	O
+,	O
+the	O
+results	O
+indicate	O
+that	O
+repeated	O
+exposure	O
+to	O
+amphetamine	O
+or	O
+apomorphine	O
+overcomes	O
+the	O
+context	O
+-	O
+dependent	O
+component	O
+of	O
+sensitization	O
+of	O
+amphetamine	O
+-	O
+or	O
+apomorphine	O
+-	O
+induced	O
+stereotyped	O
+behavior	O
+.	O
+
+Testing	O
+for	O
+serum	B-GENE
+IgM	I-GENE
+binding	O
+to	O
+GM1	O
+ganglioside	O
+in	O
+clinical	O
+practice	O
+.	O
+
+Objective	O
+responses	O
+also	O
+occurred	O
+in	O
+studies	O
+that	O
+explored	O
+sequential	O
+use	O
+of	O
+exemestane	O
+after	O
+failure	O
+of	O
+aminoglutethimide	O
+(	O
+26	O
+%	O
+with	O
+exemestane	O
+200	O
+mg	O
+/	O
+day	O
+)	O
+or	O
+other	O
+nonsteroidal	O
+aromatase	B-GENE
+inhibitors	O
+(	O
+6	O
+.	O
+6	O
+%	O
+with	O
+exemestane	O
+25	O
+mg	O
+/	O
+day	O
+)	O
+.	O
+
+The	O
+science	O
+of	O
+tissue	O
+engineering	O
+.	O
+
+Endonuclease	B-GENE
+III	I-GENE
+(	O
+Nth	B-GENE
+)	O
+of	O
+Escherichia	O
+coli	O
+is	O
+a	O
+DNA	B-GENE
+glycosylase	I-GENE
+essential	O
+for	O
+the	O
+removal	O
+of	O
+oxidised	O
+pyrimidine	O
+base	O
+residues	O
+from	O
+DNA	O
+.	O
+
+The	O
+duration	O
+of	O
+reactive	O
+hyperemia	O
+decreased	O
+with	O
+aging	O
+,	O
+but	O
+the	O
+difference	O
+between	O
+males	O
+and	O
+females	O
+was	O
+not	O
+significant	O
+at	O
+any	O
+age	O
+.	O
+
+Acquired	O
+bile	O
+duct	O
+blockage	O
+:	O
+entry	O
+of	O
+hepatobiliary	O
+agent	O
+into	O
+an	O
+intrahepatic	O
+abscess	O
+.	O
+
+Furthermore	O
+,	O
+this	O
+study	O
+looks	O
+at	O
+the	O
+impact	O
+of	O
+synthesis	O
+conditions	O
+on	O
+block	O
+length	O
+and	O
+crystallinity	O
+,	O
+and	O
+the	O
+impact	O
+of	O
+the	O
+blocking	O
+on	O
+both	O
+,	O
+crystallinity	O
+and	O
+solubility	O
+of	O
+the	O
+polymers	O
+.	O
+
+However	O
+,	O
+little	O
+was	O
+understood	O
+about	O
+the	O
+normal	O
+function	O
+of	O
+CREB	B-GENE
+-	I-GENE
+2	I-GENE
+in	O
+mammalian	O
+development	O
+or	O
+organ	O
+physiology	O
+.	O
+
+Both	O
+the	O
+MVBF	O
+and	O
+the	O
+maximum	O
+EMG	O
+activity	O
+in	O
+the	O
+right	O
+masseter	O
+and	O
+the	O
+left	O
+anterior	O
+temporalis	O
+muscles	O
+were	O
+significantly	O
+decreased	O
+during	O
+muscle	O
+pain	O
+when	O
+the	O
+subjects	O
+bit	O
+on	O
+the	O
+painful	O
+side	O
+.	O
+
+The	O
+total	O
+alkaloids	O
+contained	O
+in	O
+the	O
+peel	O
+of	O
+Atzimba	O
+,	O
+Lopez	O
+,	O
+Marciana	O
+,	O
+Montsama	O
+,	O
+Murca	O
+,	O
+and	O
+Puebla	O
+was	O
+lower	O
+than	O
+the	O
+limits	O
+recommended	O
+for	O
+food	O
+safety	O
+.	O
+
+The	O
+detection	O
+success	O
+rate	O
+was	O
+determined	O
+for	O
+different	O
+markers	O
+using	O
+this	O
+MEK	B-GENE
+.	O
+
+Herein	O
+,	O
+we	O
+show	O
+that	O
+Smad3	B-GENE
+physically	O
+interacts	O
+with	O
+the	O
+HMG	B-GENE
+box	O
+domain	O
+of	O
+LEF1	B-GENE
+and	O
+that	O
+TGFbeta	B-GENE
+and	O
+Wnt	B-GENE
+pathways	O
+synergize	O
+to	O
+activate	O
+transcription	O
+of	O
+the	O
+Xenopus	O
+homeobox	O
+gene	O
+twin	B-GENE
+(	O
+Xtwn	B-GENE
+)	O
+.	O
+
+The	O
+transmembrane	O
+topology	O
+of	O
+Na	O
+(	O
++	O
+)	O
+/	O
+H	O
+(	O
++	O
+)	O
+exchanger	O
+NHE3	B-GENE
+has	O
+been	O
+studied	O
+using	O
+in	O
+vitro	O
+transcription	O
+/	O
+translation	O
+of	O
+two	O
+types	O
+of	O
+fusion	O
+vectors	O
+designed	O
+to	O
+test	O
+membrane	O
+insertion	O
+properties	O
+of	O
+cDNA	O
+sequences	O
+encoding	O
+putative	O
+NHE3	B-GENE
+membrane	O
+spanning	O
+domains	O
+(	O
+msds	O
+)	O
+.	O
+
+Members	O
+of	O
+the	O
+titin	B-GENE
+/	O
+myosin	B-GENE
+light	I-GENE
+chain	I-GENE
+kinase	I-GENE
+family	O
+play	O
+an	O
+essential	O
+role	O
+in	O
+the	O
+organization	O
+of	O
+the	O
+actin	B-GENE
+/	O
+myosin	B-GENE
+cytoskeleton	O
+,	O
+especially	O
+in	O
+sarcomere	O
+assembly	O
+and	O
+function	O
+.	O
+
+Furthermore	O
+,	O
+a	O
+pTyr317	B-GENE
+Shc	I-GENE
+phosphopeptide	I-GENE
+selectively	O
+recognized	O
+Grb2	B-GENE
+,	O
+Sos1	B-GENE
+,	O
+SHIP	B-GENE
+,	O
+and	O
+the	O
+p85	B-GENE
+subunit	I-GENE
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+'	I-GENE
+kinase	I-GENE
+from	O
+mast	O
+cells	O
+,	O
+as	O
+characterized	O
+by	O
+mass	O
+spectrometry	O
+.	O
+
+Although	O
+increased	O
+expression	O
+of	O
+the	O
+HMG	B-GENE
+-	I-GENE
+I	I-GENE
+/	I-GENE
+Y	I-GENE
+proteins	I-GENE
+is	O
+associated	O
+with	O
+cellular	O
+proliferation	O
+,	O
+neoplastic	O
+transformation	O
+,	O
+and	O
+several	O
+human	O
+cancers	O
+,	O
+the	O
+role	O
+of	O
+these	O
+proteins	O
+in	O
+the	O
+pathogenesis	O
+of	O
+malignancy	O
+remains	O
+unclear	O
+.	O
+
+The	O
+naltrexone	O
+/	O
+lofexidine	O
+combination	O
+was	O
+associated	O
+with	O
+a	O
+more	O
+rapid	O
+resolution	O
+of	O
+the	O
+opiate	O
+withdrawal	O
+syndrome	O
+than	O
+a	O
+7	O
+-	O
+day	O
+lofexidine	O
+-	O
+only	O
+treatment	O
+schedule	O
+,	O
+without	O
+substantial	O
+increases	O
+in	O
+withdrawal	O
+symptoms	O
+or	O
+hypotensive	O
+side	O
+-	O
+effects	O
+.	O
+
+The	O
+unfolded	O
+protein	O
+response	O
+regulates	O
+multiple	O
+aspects	O
+of	O
+secretory	O
+and	O
+membrane	O
+protein	O
+biogenesis	O
+and	O
+endoplasmic	O
+reticulum	O
+quality	O
+control	O
+.	O
+
+PNRC	B-GENE
+:	O
+a	O
+proline	O
+-	O
+rich	O
+nuclear	O
+receptor	O
+coregulatory	O
+protein	O
+that	O
+modulates	O
+transcriptional	O
+activation	O
+of	O
+multiple	O
+nuclear	O
+receptors	O
+including	O
+orphan	O
+receptors	O
+SF1	B-GENE
+(	O
+steroidogenic	B-GENE
+factor	I-GENE
+1	I-GENE
+)	O
+and	O
+ERRalpha1	B-GENE
+(	O
+estrogen	B-GENE
+related	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+-	I-GENE
+1	I-GENE
+)	O
+.	O
+
+Studies	O
+using	O
+a	O
+reporter	O
+plasmid	O
+with	O
+a	O
+functionally	O
+disrupted	O
+sterol	O
+-	O
+responsive	O
+element	O
+(	O
+SRE	O
+)	O
+-	O
+1	O
+revealed	O
+a	O
+reduced	O
+stimulatory	O
+response	O
+to	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+.	O
+
+However	O
+,	O
+there	O
+is	O
+still	O
+a	O
+subset	O
+of	O
+tumors	O
+that	O
+displayed	O
+no	O
+changes	O
+in	O
+these	O
+genes	O
+.	O
+
+Bailey	O
+Instruments	O
+and	O
+Owen	O
+Mumford	O
+filaments	O
+were	O
+the	O
+most	O
+accurate	O
+with	O
+100	O
+%	O
+buckling	O
+within	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+g	O
+of	O
+10	O
+g	O
+.	O
+
+PARTICIPANTS	O
+:	O
+Convenience	O
+sample	O
+of	O
+ambulatory	O
+outpatients	O
+with	O
+hereditary	O
+motor	O
+and	O
+sensory	O
+neuropathy	O
+,	O
+type	O
+I	O
+(	O
+n	O
+=	O
+9	O
+)	O
+,	O
+myotonic	O
+muscular	O
+dystrophy	O
+(	O
+n	O
+=	O
+10	O
+)	O
+,	O
+and	O
+able	O
+-	O
+bodied	O
+controls	O
+(	O
+n	O
+=	O
+11	O
+)	O
+.	O
+
+The	O
+effect	O
+of	O
+water	O
+deprivation	O
+for	O
+19	O
+h	O
+on	O
+renal	O
+Na	O
+excretion	O
+of	O
+conscious	O
+adrenalectomized	O
+(	O
+ADX	O
+)	O
+sheep	O
+maintained	O
+on	O
+a	O
+constant	O
+intravenous	O
+infusion	O
+of	O
+aldosterone	O
+and	O
+cortisol	O
+(	O
+ADX	O
+-	O
+constant	O
+steroid	O
+sheep	O
+)	O
+was	O
+investigated	O
+.	O
+
+Neither	O
+is	O
+it	O
+a	O
+major	O
+cause	O
+of	O
+rehydration	O
+-	O
+induced	O
+renal	O
+Na	O
+retention	O
+.	O
+
+CONCLUSION	O
+:	O
+Rheumatic	O
+fever	O
+in	O
+the	O
+Nazareth	O
+area	O
+is	O
+still	O
+manifest	O
+.	O
+
+Antithrombin	B-GENE
+III	I-GENE
+deficiency	O
+:	O
+when	O
+substitute	O
+,	O
+when	O
+heparin	O
+?	O
+Thrombosis	O
+ABC	O
+,	O
+3	O
+:	O
+The	O
+role	O
+of	O
+antithrombin	B-GENE
+III	I-GENE
+
+Specific	O
+class	B-GENE
+I	I-GENE
+and	I-GENE
+II	I-GENE
+histone	I-GENE
+deacetylases	I-GENE
+(	O
+HDACs	B-GENE
+)	O
+interact	O
+in	O
+vivo	O
+with	O
+BCoR	B-GENE
+,	O
+suggesting	O
+that	O
+BCoR	B-GENE
+may	O
+functionally	O
+link	O
+these	O
+two	O
+classes	O
+of	O
+HDACs	B-GENE
+.	O
+
+This	O
+is	O
+the	O
+first	O
+example	O
+of	O
+a	O
+eukaryotic	O
+transcription	O
+factor	O
+complex	O
+containing	O
+both	O
+a	O
+MADS	B-GENE
+-	I-GENE
+box	I-GENE
+and	O
+a	O
+forkhead	B-GENE
+protein	I-GENE
+,	O
+and	O
+it	O
+has	O
+important	O
+implications	O
+for	O
+the	O
+regulation	O
+of	O
+mammalian	O
+gene	O
+expression	O
+.	O
+
+After	O
+screening	O
+the	O
+Berkeley	O
+Drosophila	O
+Genome	O
+Project	O
+database	O
+with	O
+sequences	O
+from	O
+a	O
+recently	O
+characterized	O
+Leu	B-GENE
+-	I-GENE
+rich	I-GENE
+repeats	I-GENE
+-	I-GENE
+containing	I-GENE
+G	I-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+receptor	I-GENE
+(	O
+LGR	B-GENE
+)	O
+from	O
+Drosophila	O
+(	O
+DLGR	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+,	O
+we	O
+identified	O
+a	O
+second	O
+gene	O
+for	O
+a	O
+different	O
+LGR	B-GENE
+(	O
+DLGR	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+and	O
+cloned	O
+its	O
+cDNA	O
+.	O
+
+Degenerate	O
+primers	O
+homologous	O
+to	O
+highly	O
+conserved	O
+regions	O
+of	O
+known	O
+CYP3A	B-GENE
+sequences	I-GENE
+were	O
+used	O
+for	O
+initial	O
+RT	O
+-	O
+PCRs	O
+.	O
+
+When	O
+cells	O
+were	O
+microinjected	O
+with	O
+TFOs	O
+designed	O
+to	O
+bind	O
+to	O
+a	O
+30	O
+-	O
+bp	O
+polypurine	O
+site	O
+situated	O
+between	O
+the	O
+two	O
+TK	B-GENE
+genes	I-GENE
+,	O
+recombination	O
+was	O
+observed	O
+at	O
+frequencies	O
+in	O
+the	O
+range	O
+of	O
+1	O
+%	O
+,	O
+2	O
+,	O
+500	O
+-	O
+fold	O
+above	O
+the	O
+background	O
+.	O
+
+Methyllevamisole	O
+was	O
+used	O
+as	O
+the	O
+internal	O
+standard	O
+.	O
+
+Only	O
+transcripts	O
+specific	O
+for	O
+TSGF	B-GENE
+-	I-GENE
+2	I-GENE
+are	O
+detected	O
+in	O
+ovary	O
+and	O
+testes	O
+tissues	O
+of	O
+adults	O
+as	O
+well	O
+as	O
+in	O
+puparia	O
+,	O
+while	O
+neither	O
+gene	O
+is	O
+expressed	O
+during	O
+the	O
+larval	O
+developmental	O
+stages	O
+.	O
+
+In	O
+a	O
+gel	O
+retardation	O
+assay	O
+using	O
+HepG2	O
+nuclear	O
+extracts	O
+,	O
+the	O
+5	O
+'	O
+flanking	O
+sequence	O
+from	O
+-	O
+74	O
+to	O
+-	O
+46	O
+showed	O
+a	O
+shifted	O
+band	O
+.	O
+
+Coimmunoprecipitation	O
+experiments	O
+performed	O
+in	O
+transfected	O
+cells	O
+showed	O
+that	O
+BCMA	B-GENE
+associates	O
+with	O
+TNFR	B-GENE
+-	I-GENE
+associated	I-GENE
+factor	I-GENE
+(	I-GENE
+TRAF	I-GENE
+)	I-GENE
+1	I-GENE
+,	O
+TRAF2	B-GENE
+,	O
+and	O
+TRAF3	B-GENE
+adaptor	I-GENE
+proteins	I-GENE
+.	O
+
+Since	O
+the	O
+RINX	B-GENE
+gene	I-GENE
+is	O
+likely	O
+an	O
+ortholog	O
+of	O
+the	O
+goldfish	B-GENE
+Vsx1	I-GENE
+gene	I-GENE
+,	O
+it	O
+has	O
+been	O
+named	O
+VSX1	B-GENE
+by	O
+the	O
+Human	O
+Gene	O
+Nomenclature	O
+Committee	O
+.	O
+
+The	O
+chromosomal	O
+localization	O
+on	O
+distal	O
+chromosome	O
+7	O
+places	O
+it	O
+in	O
+a	O
+cluster	O
+of	O
+imprinted	O
+genes	O
+,	O
+flanked	O
+by	O
+the	O
+previously	O
+described	O
+Tapa1	B-GENE
+and	O
+Kcnq1	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+evaluate	O
+the	O
+sensitivity	O
+and	O
+specificity	O
+of	O
+AMP	O
+CT	O
+(	O
+Gen	O
+-	O
+Probe	O
+Incorporated	O
+,	O
+San	O
+Diego	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+on	O
+urogenital	O
+specimens	O
+taken	O
+from	O
+symptomatic	O
+patients	O
+and	O
+on	O
+first	O
+void	O
+urine	O
+(	O
+FVU	O
+)	O
+specimens	O
+from	O
+asymptomatic	O
+patients	O
+.	O
+
+The	O
+linear	O
+plasmid	O
+pCLU1	O
+from	O
+the	O
+yeast	O
+Kluyveromyces	O
+lactis	O
+normally	O
+replicates	O
+in	O
+the	O
+cytoplasm	O
+,	O
+with	O
+the	O
+aid	O
+of	O
+the	O
+helper	O
+linear	O
+plasmid	O
+pGKL2	O
+,	O
+using	O
+terminal	B-GENE
+protein	I-GENE
+(	O
+TP	B-GENE
+)	O
+as	O
+a	O
+primer	O
+.	O
+
+The	O
+repetitive	O
+ETn	B-GENE
+(	O
+early	B-GENE
+transposon	I-GENE
+)	O
+family	O
+of	O
+sequences	O
+represents	O
+an	O
+active	O
+"	O
+mobile	O
+mutagen	O
+"	O
+in	O
+the	O
+mouse	O
+genome	O
+.	O
+
+The	O
+two	O
+main	O
+experimental	O
+variables	O
+were	O
+the	O
+attended	O
+hemifield	O
+(	O
+left	O
+or	O
+right	O
+)	O
+and	O
+the	O
+proportion	O
+of	O
+trials	O
+requiring	O
+a	O
+shift	O
+within	O
+that	O
+hemifield	O
+(	O
+20	O
+%	O
+or	O
+80	O
+%	O
+)	O
+.	O
+
+The	O
+measurement	O
+of	O
+NO	O
+in	O
+biological	O
+systems	O
+using	O
+chemiluminescence	O
+.	O
+
+Biochemical	O
+examinations	O
+of	O
+calcium	O
+-	O
+phosphorus	O
+metabolism	O
+included	O
+ions	O
+and	O
+PTH	B-GENE
+concentrations	O
+in	O
+blood	O
+serum	O
+,	O
+and	O
+the	O
+activity	O
+of	O
+bone	O
+isoenzyme	O
+of	O
+AP	B-GENE
+.	O
+
+Atorvastatin	O
+was	O
+the	O
+most	O
+cost	O
+-	O
+effective	O
+HMG	B-GENE
+-	I-GENE
+CoA	I-GENE
+reductase	I-GENE
+inhibitor	O
+.	O
+
+Pharmacoeconomic	O
+assessment	O
+of	O
+HMG	B-GENE
+-	I-GENE
+CoA	I-GENE
+reductase	I-GENE
+inhibitor	O
+therapy	O
+:	O
+an	O
+analysis	O
+based	O
+on	O
+the	O
+CURVES	O
+study	O
+.	O
+
+Interestingly	O
+,	O
+although	O
+E	O
+domains	O
+of	O
+these	O
+two	O
+receptors	O
+are	O
+much	O
+less	O
+conserved	O
+,	O
+replacement	O
+of	O
+this	O
+domain	O
+in	O
+rtER	B-GENE
+by	O
+its	O
+human	O
+counterpart	O
+resulted	O
+in	O
+higher	O
+estradiol	O
+sensitivity	O
+but	O
+no	O
+increase	O
+in	O
+the	O
+magnitude	O
+of	O
+transactivation	O
+.	O
+
+G	O
+-	O
+DNA	O
+is	O
+a	O
+four	O
+-	O
+stranded	O
+DNA	O
+structure	O
+with	O
+diverse	O
+putative	O
+biological	O
+roles	O
+.	O
+
+The	O
+effectiveness	O
+of	O
+NRT	O
+appears	O
+to	O
+be	O
+largely	O
+independent	O
+of	O
+the	O
+intensity	O
+of	O
+additional	O
+support	O
+provided	O
+to	O
+the	O
+smoker	O
+.	O
+
+8	O
+%	O
+(	O
+95	O
+%	O
+CI	O
+,	O
+21	O
+.	O
+3	O
+-	O
+44	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+action	O
+of	O
+GLP	B-GENE
+-	I-GENE
+1	I-GENE
+at	O
+the	O
+CRE	O
+was	O
+not	O
+blocked	O
+by	O
+cotransfection	O
+with	O
+M1	B-GENE
+-	I-GENE
+CREB	I-GENE
+,	O
+an	O
+isoform	O
+that	O
+lacks	O
+a	O
+consensus	O
+serine	O
+residue	O
+serving	O
+as	O
+substrate	O
+for	O
+PKA	B-GENE
+-	O
+mediated	O
+phosphorylation	O
+.	O
+
+Because	O
+all	O
+PDGFbetaR	B-GENE
+fusions	I-GENE
+described	O
+thus	O
+far	O
+result	O
+in	O
+splicing	O
+to	O
+a	O
+common	O
+exon	O
+of	O
+this	O
+gene	O
+,	O
+we	O
+performed	O
+5	O
+'	O
+-	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+PCR	O
+on	O
+patient	O
+RNA	O
+.	O
+
+CONCLUSIONS	O
+:	O
+In	O
+essential	O
+hypertension	O
+an	O
+acute	O
+protein	O
+load	O
+induces	O
+a	O
+decrease	O
+in	O
+GFR	O
+that	O
+may	O
+normalize	O
+under	O
+antihypertensive	O
+treatment	O
+.	O
+
+This	O
+finding	O
+suggested	O
+that	O
+the	O
+PI3K	B-GENE
+-	O
+Akt	B-GENE
+activation	O
+pathway	O
+plays	O
+some	O
+role	O
+in	O
+the	O
+antiapoptotic	O
+effect	O
+of	O
+EPO	B-GENE
+.	O
+
+Nine	O
+DNA	O
+fragments	O
+that	O
+were	O
+specifically	O
+recognized	O
+and	O
+bound	O
+by	O
+histidine	O
+-	O
+tagged	O
+AdpA	B-GENE
+were	O
+isolated	O
+by	O
+cycles	O
+of	O
+a	O
+gel	O
+mobility	O
+shift	O
+-	O
+PCR	O
+method	O
+.	O
+
+To	O
+determine	O
+whether	O
+the	O
+NTP	O
+-	O
+binding	O
+motif	O
+is	O
+important	O
+for	O
+Rad24	B-GENE
+function	O
+,	O
+we	O
+mutated	O
+the	O
+conserved	O
+lysine	O
+(	O
+115	O
+)	O
+residue	O
+in	O
+this	O
+motif	O
+.	O
+
+The	O
+carboxyl	O
+-	O
+terminal	O
+proline	O
+-	O
+rich	O
+domain	O
+of	O
+SOS1	B-GENE
+is	O
+involved	O
+in	O
+the	O
+interaction	O
+with	O
+the	O
+PLC	B-GENE
+-	I-GENE
+gamma1	I-GENE
+SH3	B-GENE
+domain	I-GENE
+.	O
+
+From	O
+transient	O
+expression	O
+studies	O
+,	O
+we	O
+could	O
+demonstrate	O
+that	O
+the	O
+SH3	B-GENE
+domain	I-GENE
+of	O
+PLC	B-GENE
+-	I-GENE
+gamma1	I-GENE
+is	O
+necessary	O
+for	O
+the	O
+association	O
+with	O
+SOS1	B-GENE
+in	O
+vivo	O
+.	O
+
+Wnt	B-GENE
+-	I-GENE
+1	I-GENE
+overexpression	O
+in	O
+mammary	O
+epithelial	O
+cells	O
+induced	O
+cyclin	B-GENE
+D1	I-GENE
+mRNA	I-GENE
+and	O
+targeted	O
+overexpression	O
+of	O
+Wnt	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+the	O
+mammary	O
+gland	O
+of	O
+transgenic	O
+mice	O
+increased	O
+both	O
+ILK	B-GENE
+activity	O
+and	O
+cyclin	B-GENE
+D1	I-GENE
+levels	O
+.	O
+
+Intravenous	O
+versus	O
+oral	O
+administration	O
+of	O
+amitriptyline	O
+in	O
+patients	O
+with	O
+major	O
+depression	O
+.	O
+
+Deletion	O
+of	O
+the	O
+RVH	B-GENE
+domain	I-GENE
+resulted	O
+in	O
+loss	O
+of	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+-	O
+dependent	O
+activation	O
+.	O
+
+Logistic	O
+regression	O
+analysis	O
+revealed	O
+that	O
+physicians	O
+were	O
+3	O
+.	O
+6	O
+times	O
+more	O
+likely	O
+to	O
+detect	O
+thin	O
+lesions	O
+(	O
+<	O
+/	O
+=	O
+0	O
+.	O
+75	O
+mm	O
+)	O
+compared	O
+with	O
+nonphysician	O
+detectors	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+95	O
+%	O
+CI	O
+]	O
+,	O
+2	O
+.	O
+1	O
+,	O
+6	O
+.	O
+5	O
+;	O
+P	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+Erythema	O
+exsudativum	O
+multiforme	O
+induced	O
+by	O
+granulocyte	B-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+in	O
+an	O
+allogeneic	O
+peripheral	O
+blood	O
+stem	O
+cell	O
+donor	O
+.	O
+
+VaI	O
+and	O
+VaII	O
+co	O
+-	O
+immunoprecipitated	O
+with	O
+ErbB2	B-GENE
+,	O
+but	O
+not	O
+with	O
+ErbB1	B-GENE
+,	O
+ErbB3	B-GENE
+,	O
+or	O
+ErbB4	B-GENE
+.	O
+
+While	O
+interactions	O
+of	O
+WT	O
+and	O
+variant	O
+TGF	B-GENE
+-	I-GENE
+alpha	I-GENE
+with	O
+the	O
+ErbBs	B-GENE
+all	O
+result	O
+in	O
+ErbB2	B-GENE
+activation	O
+,	O
+they	O
+produce	O
+different	O
+biological	O
+consequences	O
+,	O
+suggesting	O
+that	O
+the	O
+various	O
+TGF	B-GENE
+-	I-GENE
+alpha	I-GENE
+precursors	I-GENE
+differentially	O
+modulate	O
+ErbB	B-GENE
+signaling	O
+.	O
+
+In	O
+contrast	O
+to	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+E2F	I-GENE
+-	I-GENE
+3	I-GENE
+,	O
+which	O
+is	O
+expressed	O
+only	O
+at	O
+the	O
+G1	O
+/	O
+S	O
+boundary	O
+,	O
+E2F	B-GENE
+-	I-GENE
+3B	I-GENE
+is	O
+detected	O
+throughout	O
+the	O
+cell	O
+cycle	O
+with	O
+peak	O
+levels	O
+in	O
+GO	O
+where	O
+it	O
+is	O
+associated	O
+with	O
+Rb	B-GENE
+.	O
+
+Developmental	O
+toxicity	O
+of	O
+the	O
+class	O
+III	O
+antiarrhythmic	O
+agent	O
+almokalant	O
+in	O
+mice	O
+.	O
+
+In	O
+addition	O
+to	O
+its	O
+effect	O
+in	O
+augmenting	O
+the	O
+neutrophil	O
+response	O
+to	O
+eccentric	O
+exercise	O
+,	O
+vitamin	O
+E	O
+causes	O
+a	O
+greater	O
+increase	O
+in	O
+circulating	O
+creatine	B-GENE
+kinase	I-GENE
+activity	O
+,	O
+perhaps	O
+indicating	O
+increased	O
+skeletal	O
+muscle	O
+repair	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+authors	O
+emphasize	O
+that	O
+the	O
+initial	O
+management	O
+of	O
+primary	O
+STS	O
+should	O
+be	O
+adequate	O
+and	O
+suggest	O
+that	O
+safty	O
+margin	O
+of	O
+>	O
+or	O
+=	O
+2	O
+cm	O
+should	O
+be	O
+adhered	O
+to	O
+.	O
+
+Measurements	O
+were	O
+compared	O
+with	O
+two	O
+computerised	O
+treatment	O
+planning	O
+systems	O
+-	O
+-	O
+Theraplan	O
+VO5B	O
+and	O
+ADAC	O
+Pinnacle3	O
+V4	O
+.	O
+0b	O
+.	O
+
+Activation	O
+was	O
+biphasic	O
+;	O
+peaking	O
+at	O
+5	O
+-	O
+10	O
+min	O
+and	O
+24	O
+h	O
+after	O
+treatment	O
+.	O
+
+Whereas	O
+MARTA1	B-GENE
+is	O
+clearly	O
+detectable	O
+in	O
+crude	O
+lysates	O
+,	O
+cytosolic	O
+and	O
+ribosomal	O
+salt	O
+-	O
+wash	O
+fractions	O
+,	O
+and	O
+in	O
+nuclear	O
+extracts	O
+,	O
+MARTA2	B-GENE
+is	O
+preferentially	O
+found	O
+in	O
+the	O
+ribosomal	O
+salt	O
+-	O
+wash	O
+preparation	O
+.	O
+
+Five	O
+of	O
+the	O
+PDP1	B-GENE
+isoforms	I-GENE
+differ	O
+by	O
+the	O
+substitution	O
+or	O
+insertion	O
+of	O
+amino	O
+acids	O
+at	O
+or	O
+near	O
+the	O
+N	O
+-	O
+terminal	O
+of	O
+the	O
+protein	O
+.	O
+
+The	O
+optimum	O
+technique	O
+for	O
+the	O
+pathological	O
+examination	O
+of	O
+sentinel	O
+lymph	O
+nodes	O
+(	O
+SLNs	O
+)	O
+is	O
+still	O
+under	O
+debate	O
+.	O
+
+Partial	O
+correction	O
+of	O
+anemia	O
+with	O
+recombinant	B-GENE
+human	I-GENE
+erythropoietin	I-GENE
+likely	O
+reduces	O
+left	O
+ventricular	O
+mass	O
+and	O
+volume	O
+.	O
+
+This	O
+study	O
+demonstrated	O
+that	O
+the	O
+PFA	O
+-	O
+100	O
+analyzer	O
+can	O
+accurately	O
+assess	O
+vWF	B-GENE
+-	O
+dependent	O
+platelet	O
+function	O
+and	O
+detect	O
+other	O
+platelet	O
+defects	O
+under	O
+high	O
+shear	O
+stress	O
+in	O
+complex	O
+patient	O
+populations	O
+.	O
+
+We	O
+recently	O
+reported	O
+the	O
+molecular	O
+cloning	O
+of	O
+a	O
+PL	B-GENE
+scramblase	I-GENE
+of	O
+human	O
+(	O
+HuPLSCR1	B-GENE
+)	O
+and	O
+mouse	O
+origin	O
+,	O
+respectively	O
+.	O
+
+To	O
+analyze	O
+the	O
+regulatory	O
+activity	O
+of	O
+Gtx	B-GENE
+,	O
+we	O
+first	O
+identified	O
+the	O
+optimal	O
+Gtx	B-GENE
+-	I-GENE
+binding	I-GENE
+sequence	I-GENE
+using	O
+an	O
+in	O
+vitro	O
+DNA	O
+-	O
+binding	O
+assay	O
+.	O
+
+Using	O
+an	O
+oligomer	O
+duplex	O
+5	O
+'	O
+-	O
+A	O
+(	O
+GGGTTA	O
+)	O
+(	O
+5	O
+)	O
+-	O
+3	O
+'	O
+/	O
+5	O
+'	O
+-	O
+(	O
+TAACCC	O
+)	O
+(	O
+5	O
+)	O
+T	O
+-	O
+3	O
+'	O
+as	O
+a	O
+template	O
+-	O
+primer	O
+,	O
+we	O
+show	O
+that	O
+both	O
+the	O
+Klenow	B-GENE
+fragment	I-GENE
+of	I-GENE
+Escherichia	I-GENE
+coli	I-GENE
+DNA	I-GENE
+polymerase	I-GENE
+I	I-GENE
+and	O
+HIV	B-GENE
+reverse	I-GENE
+transcriptase	I-GENE
+could	O
+expand	O
+telomere	O
+DNA	O
+sequences	O
+as	O
+well	O
+,	O
+giving	O
+products	O
+greater	O
+than	O
+the	O
+size	O
+of	O
+the	O
+template	O
+DNA	O
+.	O
+
+Cdk2	B-GENE
+and	O
+MAPK	B-GENE
+precipitates	O
+from	O
+untreated	O
+tumor	O
+lysates	O
+phosphorylated	O
+recombinant	B-GENE
+wild	I-GENE
+-	I-GENE
+type	I-GENE
+p27	I-GENE
+but	O
+not	O
+the	O
+T187A	O
+mutant	O
+in	O
+vitro	O
+.	O
+
+The	O
+loss	O
+of	O
+avirulence	O
+activity	O
+because	O
+of	O
+mutations	O
+in	O
+the	O
+acidic	O
+transcriptional	O
+activation	O
+domain	O
+was	O
+restored	O
+by	O
+addition	O
+of	O
+the	O
+activation	O
+domain	O
+from	O
+the	O
+herpes	B-GENE
+simplex	I-GENE
+viral	I-GENE
+protein	I-GENE
+VP16	I-GENE
+.	O
+
+Mutations	O
+in	O
+the	O
+RP2	B-GENE
+locus	I-GENE
+at	I-GENE
+Xp11	I-GENE
+.	I-GENE
+3	I-GENE
+were	O
+found	O
+in	O
+a	O
+further	O
+10	O
+-	O
+20	O
+%	O
+of	O
+XLRP	O
+patients	O
+,	O
+as	O
+predicted	O
+from	O
+linkage	O
+studies	O
+.	O
+
+Subsequently	O
+,	O
+HD	O
+inhibited	O
+healing	O
+because	O
+it	O
+significantly	O
+delayed	O
+epithelialization	O
+and	O
+caused	O
+protracted	O
+inflammation	O
+.	O
+
+The	O
+effectiveness	O
+of	O
+the	O
+haemodialysate	O
+Solcoseryl	O
+for	O
+second	O
+-	O
+intention	O
+wound	O
+healing	O
+in	O
+horses	O
+and	O
+ponies	O
+.	O
+
+Although	O
+there	O
+is	O
+little	O
+evidence	O
+that	O
+diet	O
+composition	O
+plays	O
+a	O
+clinically	O
+important	O
+role	O
+in	O
+the	O
+absorption	O
+or	O
+expenditure	O
+of	O
+energy	O
+,	O
+it	O
+does	O
+appear	O
+to	O
+play	O
+a	O
+role	O
+in	O
+food	O
+intake	O
+.	O
+
+These	O
+findings	O
+were	O
+reinforced	O
+by	O
+an	O
+analysis	O
+that	O
+was	O
+restricted	O
+to	O
+living	O
+donor	O
+transplants	O
+without	O
+acute	O
+rejection	O
+.	O
+
+The	O
+genome	O
+of	O
+the	O
+human	O
+herpesvirus	O
+8	O
+(	O
+HHV	O
+-	O
+8	O
+)	O
+contains	O
+a	O
+cluster	O
+of	O
+open	O
+reading	O
+frames	O
+(	O
+ORFs	O
+)	O
+encoding	O
+proteins	O
+with	O
+homology	O
+to	O
+the	O
+cellular	O
+transcription	O
+factors	O
+of	O
+the	O
+interferon	B-GENE
+regulatory	I-GENE
+factor	I-GENE
+(	O
+IRF	B-GENE
+)	O
+family	O
+.	O
+
+Despite	O
+these	O
+limitations	O
+the	O
+CHIME	O
+monitor	O
+provides	O
+an	O
+opportunity	O
+to	O
+record	O
+physiological	O
+data	O
+previously	O
+unavailable	O
+in	O
+the	O
+home	O
+.	O
+
+DATA	O
+SYNTHESIS	O
+:	O
+Intracoronary	O
+ultrasound	O
+has	O
+been	O
+shown	O
+to	O
+improve	O
+upon	O
+demonstrated	O
+weaknesses	O
+of	O
+coronary	O
+angiography	O
+.	O
+
+TB	O
+bone	O
+area	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+height	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+years	O
+in	O
+present	O
+colony	O
+(	O
+p	O
+=	O
+0	O
+.	O
+03	O
+)	O
+,	O
+and	O
+menses	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+predicted	O
+TB	O
+BMC	O
+.	O
+
+CREST	O
+syndrome	O
+;	O
+a	O
+changing	O
+clinical	O
+significance	O
+
+Troglitazone	O
+also	O
+induced	O
+an	O
+endogenous	B-GENE
+PPARgamma	I-GENE
+target	I-GENE
+gene	I-GENE
+in	O
+T24	O
+cells	O
+,	O
+adipocyte	B-GENE
+-	I-GENE
+type	I-GENE
+fatty	I-GENE
+acid	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+A	B-GENE
+-	I-GENE
+FABP	I-GENE
+)	O
+,	O
+the	O
+expression	O
+of	O
+which	O
+correlates	O
+with	O
+bladder	O
+cancer	O
+differentiation	O
+.	O
+
+The	O
+RS447	B-GENE
+human	B-GENE
+megasatellite	I-GENE
+tandem	I-GENE
+repetitive	I-GENE
+sequence	I-GENE
+encodes	O
+a	O
+novel	O
+deubiquitinating	O
+enzyme	O
+with	O
+a	O
+functional	O
+promoter	O
+.	O
+
+Previous	O
+experience	O
+and	O
+contextual	O
+cues	O
+are	O
+essential	O
+elements	O
+in	O
+the	O
+generation	O
+of	O
+a	O
+subjective	O
+prediction	O
+.	O
+
+To	O
+characterize	O
+this	O
+effect	O
+,	O
+we	O
+looked	O
+for	O
+targets	O
+of	O
+NS1	B-GENE
+influenza	I-GENE
+virus	I-GENE
+protein	I-GENE
+among	O
+cellular	O
+translation	O
+factors	O
+.	O
+
+Collectively	O
+,	O
+these	O
+and	O
+previously	O
+published	O
+data	O
+suggest	O
+a	O
+model	O
+where	O
+NS1	B-GENE
+recruits	O
+eIF4GI	B-GENE
+specifically	O
+to	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+(	O
+5	O
+'	O
+UTR	O
+)	O
+of	O
+the	O
+viral	O
+mRNA	O
+,	O
+allowing	O
+for	O
+the	O
+preferential	O
+translation	O
+of	O
+the	O
+influenza	O
+virus	O
+messengers	O
+.	O
+
+Eukaryotic	B-GENE
+translation	I-GENE
+initiation	I-GENE
+factor	I-GENE
+4GI	I-GENE
+is	O
+a	O
+cellular	O
+target	O
+for	O
+NS1	B-GENE
+protein	I-GENE
+,	O
+a	O
+translational	O
+activator	O
+of	O
+influenza	O
+virus	O
+.	O
+
+(	O
+iii	O
+)	O
+In	O
+these	O
+cells	O
+,	O
+PKCbeta	B-GENE
+plays	O
+a	O
+unique	O
+Ras	B-GENE
+-	O
+independent	O
+role	O
+in	O
+mediating	O
+insulin	B-GENE
+but	O
+not	O
+EGF	B-GENE
+or	O
+other	O
+growth	O
+factor	O
+mitogenic	O
+signals	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+not	O
+known	O
+whether	O
+the	O
+recently	O
+identified	O
+isoforms	O
+Vav2	B-GENE
+and	O
+Vav3	B-GENE
+,	O
+which	O
+are	O
+broadly	O
+expressed	O
+,	O
+can	O
+couple	O
+with	O
+similar	O
+classes	O
+of	O
+receptors	O
+,	O
+nor	O
+is	O
+it	O
+known	O
+whether	O
+all	O
+Vav	B-GENE
+isoforms	I-GENE
+possess	O
+identical	O
+functional	O
+activities	O
+.	O
+
+Transcriptional	O
+regulation	O
+of	O
+fbp1	B-GENE
+promoter	I-GENE
+constructs	I-GENE
+containing	O
+only	O
+UAS1	O
+or	O
+UAS2	O
+confirms	O
+that	O
+the	O
+PKA	B-GENE
+and	O
+MAPK	B-GENE
+regulation	O
+is	O
+targeted	O
+to	O
+both	O
+sites	O
+.	O
+
+X	O
+-	O
+ray	O
+crystallographic	O
+data	O
+show	O
+that	O
+the	O
+PLZF	B-GENE
+BTB	B-GENE
+/	O
+POZ	O
+domain	O
+forms	O
+an	O
+obligate	O
+homodimer	O
+via	O
+an	O
+extensive	O
+interface	O
+.	O
+
+The	O
+ability	O
+of	O
+SMRT	B-GENE
+to	O
+associate	O
+with	O
+these	O
+transcription	O
+factors	O
+and	O
+thereby	O
+to	O
+mediate	O
+repression	O
+is	O
+strongly	O
+inhibited	O
+by	O
+activation	O
+of	O
+tyrosine	B-GENE
+kinase	I-GENE
+signaling	O
+pathways	O
+,	O
+such	O
+as	O
+that	O
+represented	O
+by	O
+the	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+ketamine	O
+-	O
+treated	O
+rats	O
+had	O
+more	O
+neurons	O
+and	O
+glial	O
+cells	O
+surrounding	O
+the	O
+ventricles	O
+.	O
+
+The	O
+differences	O
+were	O
+as	O
+follows	O
+:	O
+for	O
+overall	O
+response	O
+rate	O
+p	O
+=	O
+0	O
+.	O
+004	O
+;	O
+power	O
+(	O
+for	O
+p	O
+=	O
+0	O
+.	O
+05	O
+)	O
+85	O
+%	O
+;	O
+for	O
+survival	O
+p	O
+=	O
+0	O
+.	O
+09	O
+;	O
+for	O
+grade	O
+IV	O
+granulocytopenia	O
+p	O
+=	O
+0	O
+.	O
+3	O
+;	O
+and	O
+for	O
+febrile	O
+neutropenia	O
+p	O
+=	O
+0	O
+.	O
+61	O
+.	O
+
+Patients	O
+were	O
+randomly	O
+assigned	O
+to	O
+treatment	O
+with	O
+the	O
+ACE	B-GENE
+inhibitor	O
+perindopril	O
+(	O
+and	O
+the	O
+diuretic	O
+indapamide	O
+for	O
+those	O
+with	O
+no	O
+definite	O
+indication	O
+for	O
+or	O
+contraindication	O
+to	O
+treatment	O
+with	O
+a	O
+diuretic	O
+)	O
+or	O
+matching	O
+placebo	O
+(	O
+s	O
+)	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+the	O
+open	O
+-	O
+section	O
+effect	O
+decreases	O
+the	O
+torsional	O
+stiffness	O
+and	O
+stress	O
+concentration	O
+effects	O
+decrease	O
+the	O
+torsional	O
+strength	O
+of	O
+a	O
+long	O
+bone	O
+with	O
+a	O
+longitudinal	O
+defect	O
+.	O
+
+These	O
+regions	O
+may	O
+be	O
+differentially	O
+involved	O
+in	O
+tissue	O
+-	O
+specificity	O
+,	O
+and	O
+/	O
+or	O
+circadian	O
+regulation	O
+,	O
+of	O
+the	O
+human	B-GENE
+hPer1	I-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+Additionally	O
+,	O
+putative	O
+CF1	B-GENE
+/	O
+USP	B-GENE
+and	O
+Broad	B-GENE
+Complex	I-GENE
+Z2	I-GENE
+transcription	O
+factor	O
+elements	O
+were	O
+found	O
+in	O
+the	O
+upstream	O
+regions	O
+of	O
+MIH	B-GENE
+and	O
+MO	B-GENE
+-	I-GENE
+IH	I-GENE
+genes	O
+respectively	O
+.	O
+
+Sequence	O
+analysis	O
+reveals	O
+that	O
+the	O
+newly	O
+discovered	O
+oasA2	B-GENE
+gene	I-GENE
+represents	O
+a	O
+pseudogene	O
+that	O
+is	O
+still	O
+transcribed	O
+,	O
+but	O
+is	O
+not	O
+functionally	O
+translated	O
+.	O
+
+Genomic	O
+and	O
+functional	O
+characterization	O
+of	O
+the	O
+oas	B-GENE
+gene	I-GENE
+family	I-GENE
+encoding	O
+O	B-GENE
+-	I-GENE
+acetylserine	I-GENE
+(	I-GENE
+thiol	I-GENE
+)	I-GENE
+lyases	I-GENE
+,	O
+enzymes	O
+catalyzing	O
+the	O
+final	O
+step	O
+in	O
+cysteine	O
+biosynthesis	O
+in	O
+Arabidopsis	O
+thaliana	O
+.	O
+
+Two	O
+distinct	O
+recessive	O
+susceptibility	O
+loci	O
+for	O
+vasculitis	O
+were	O
+mapped	O
+on	O
+chromosome	O
+(	O
+Chr	O
+)	O
+4	O
+at	O
+D4Mit89	B-GENE
+and	O
+D4Mit147	B-GENE
+in	O
+both	O
+progenies	O
+.	O
+
+Further	O
+characterization	O
+of	O
+these	O
+putative	O
+Hoxa	B-GENE
+-	I-GENE
+1	I-GENE
+target	I-GENE
+genes	I-GENE
+will	O
+aid	O
+in	O
+delineating	O
+the	O
+functions	O
+of	O
+the	O
+Hoxa	B-GENE
+-	I-GENE
+1	I-GENE
+protein	I-GENE
+in	O
+the	O
+differentiation	O
+processes	O
+which	O
+occur	O
+during	O
+embryogenesis	O
+.	O
+
+The	O
+ability	O
+of	O
+U6	B-GENE
+-	O
+U57	B-GENE
+mutants	O
+to	O
+influence	O
+the	O
+fidelity	O
+of	O
+both	O
+branch	O
+site	O
+and	O
+3	O
+'	O
+splice	O
+site	O
+recognition	O
+suggests	O
+that	O
+this	O
+nucleotide	O
+may	O
+participate	O
+in	O
+the	O
+formation	O
+of	O
+the	O
+active	O
+site	O
+(	O
+s	O
+)	O
+of	O
+the	O
+spliceosome	O
+.	O
+
+We	O
+have	O
+determined	O
+the	O
+structure	O
+of	O
+the	O
+WNT	B-GENE
+-	I-GENE
+2B	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+role	O
+of	O
+daunorubicin	O
+in	O
+induction	O
+therapy	O
+for	O
+adult	O
+acute	O
+myeloid	O
+leukemia	O
+
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+induced	O
+a	O
+dose	O
+-	O
+and	O
+time	O
+-	O
+dependent	O
+increase	O
+in	O
+cyclooxygenase	B-GENE
+-	I-GENE
+2	I-GENE
+(	O
+COX	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+expression	O
+and	O
+PGE2	O
+formation	O
+in	O
+human	O
+NCI	O
+-	O
+H292	O
+epithelial	O
+cells	O
+.	O
+
+The	O
+therapy	O
+time	O
+to	O
+deliver	O
+the	O
+NCS	O
+therapeutic	O
+dose	O
+of	O
+10000	O
+RBE	O
+-	O
+cGy	O
+,	O
+is	O
+27	O
+times	O
+longer	O
+when	O
+157Gd	O
+is	O
+used	O
+instead	O
+of	O
+10B	O
+.	O
+
+Mis3	B-GENE
+is	O
+needed	O
+for	O
+the	O
+formation	O
+of	O
+18S	B-GENE
+ribosome	I-GENE
+RNA	I-GENE
+,	O
+and	O
+may	O
+hence	O
+direct	O
+the	O
+level	O
+of	O
+proteins	O
+required	O
+for	O
+the	O
+coupling	O
+.	O
+
+Losartan	O
+Intervention	O
+For	O
+Endpoint	O
+.	O
+
+CONCLUSION	O
+:	O
+Vitrectomy	O
+for	O
+vitreous	O
+hemorrhage	O
+in	O
+Terson	O
+syndrome	O
+is	O
+a	O
+safe	O
+and	O
+effective	O
+procedure	O
+,	O
+offering	O
+a	O
+rapid	O
+and	O
+prolonged	O
+improvement	O
+in	O
+vision	O
+.	O
+
+RNA	O
+in	O
+situ	O
+hybridization	O
+on	O
+brain	O
+sections	O
+of	O
+normal	O
+human	O
+embryos	O
+revealed	O
+a	O
+strong	O
+labeling	O
+in	O
+restricted	O
+areas	O
+of	O
+the	O
+cerebral	O
+cortex	O
+.	O
+
+To	O
+facilitate	O
+manipulation	O
+of	O
+large	O
+genomic	O
+sequences	O
+,	O
+we	O
+developed	O
+a	O
+method	O
+of	O
+converting	O
+Escherichia	O
+coli	O
+P1	O
+artificial	O
+chromosomes	O
+(	O
+PACs	O
+)	O
+into	O
+yeast	O
+artificial	O
+chromosomes	O
+(	O
+YACs	O
+)	O
+.	O
+
+After	O
+gamma	O
+-	O
+irradiation	O
+,	O
+the	O
+majority	O
+of	O
+F9	O
+cells	O
+undergo	O
+apoptosis	O
+implying	O
+that	O
+wt	B-GENE
+-	I-GENE
+p53	I-GENE
+likely	O
+triggers	O
+pro	O
+-	O
+apoptotic	O
+gene	O
+expression	O
+in	O
+DNA	O
+damaged	O
+cells	O
+.	O
+
+Mobilization	O
+with	O
+cyclophosphamide	O
+and	O
+granulocyte	B-GENE
+-	I-GENE
+colony	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+was	O
+effective	O
+in	O
+terms	O
+of	O
+CD34	B-GENE
++	I-GENE
+cell	O
+shift	O
+to	O
+peripheral	O
+blood	O
+and	O
+the	O
+good	O
+quality	O
+autograft	O
+reliably	O
+led	O
+to	O
+haematopoetic	O
+recovery	O
+after	O
+megachemotherapy	O
+.	O
+
+This	O
+suggests	O
+that	O
+cardiovascular	O
+magnetic	O
+resonance	O
+is	O
+the	O
+preferred	O
+technique	O
+for	O
+volume	O
+and	O
+ejection	O
+fraction	O
+estimation	O
+in	O
+heart	O
+failure	O
+patients	O
+,	O
+because	O
+of	O
+its	O
+3D	O
+approach	O
+for	O
+non	O
+-	O
+symmetric	O
+ventricles	O
+and	O
+superior	O
+image	O
+quality	O
+.	O
+
+A	O
+degenerate	O
+DNA	O
+transposon	O
+,	O
+Pat	B-GENE
+,	O
+was	O
+identified	O
+in	O
+the	O
+genomes	O
+of	O
+various	O
+wild	O
+-	O
+type	O
+strains	O
+of	O
+the	O
+filamentous	O
+fungus	O
+Podospora	O
+anserina	O
+.	O
+
+However	O
+,	O
+the	O
+presence	O
+of	O
+Tax	B-GENE
+I	I-GENE
+increased	O
+the	O
+extent	O
+and	O
+altered	O
+the	O
+profile	O
+of	O
+proteins	O
+binding	O
+TRE	B-GENE
+-	I-GENE
+2	I-GENE
+in	O
+vivo	O
+.	O
+
+We	O
+have	O
+also	O
+identified	O
+a	O
+functional	O
+domain	O
+in	O
+the	O
+ORF	O
+50	O
+protein	O
+,	O
+an	O
+immediate	B-GENE
+-	I-GENE
+early	I-GENE
+gene	I-GENE
+product	I-GENE
+that	O
+is	O
+mainly	O
+encoded	O
+by	O
+ORF	O
+50	O
+.	O
+
+A	O
+2	O
+.	O
+3	O
+-	O
+kb	O
+full	O
+-	O
+length	O
+cDNA	O
+clone	O
+of	O
+an	O
+Atlantic	B-GENE
+halibut	I-GENE
+Mx	I-GENE
+gene	I-GENE
+was	O
+isolated	O
+from	O
+a	O
+liver	O
+cDNA	O
+library	O
+.	O
+
+PLUS	O
+-	O
+3	O
+is	O
+a	O
+new	O
+Swedish	O
+protocol	O
+of	O
+natural	O
+speech	O
+in	O
+3	O
+-	O
+year	O
+-	O
+old	O
+children	O
+.	O
+
+Once	O
+HIT	O
+II	O
+is	O
+suspected	O
+,	O
+heparin	O
+(	O
+and	O
+low	O
+-	O
+molecular	O
+-	O
+weight	O
+heparins	O
+)	O
+should	O
+be	O
+stopped	O
+immediately	O
+.	O
+
+The	O
+reduced	O
+efficiency	O
+in	O
+the	O
+glycosylase	B-GENE
+activity	O
+is	O
+also	O
+reflected	O
+in	O
+a	O
+reduced	O
+ability	O
+of	O
+S120K	B-GENE
+MutY	I-GENE
+to	O
+prevent	O
+DNA	O
+mutations	O
+in	O
+vivo	O
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+We	O
+prospectively	O
+compared	O
+the	O
+automated	O
+measurements	O
+of	O
+left	O
+ventricular	O
+ejection	O
+fraction	O
+(	O
+LVEF	O
+)	O
+and	O
+volumes	O
+from	O
+rest	O
+-	O
+injected	O
+gated	O
+Technetium	O
+99m	O
+(	O
+Tc99m	O
+)	O
+perfusion	O
+SPECT	O
+with	O
+equilibrium	O
+radionuclide	O
+angiocardiography	O
+(	O
+ERNA	O
+)	O
+in	O
+62	O
+patients	O
+and	O
+the	O
+assessment	O
+of	O
+regional	O
+function	O
+with	O
+echocardiography	O
+in	O
+22	O
+patients	O
+.	O
+
+This	O
+intracellular	O
+signaling	O
+,	O
+known	O
+as	O
+the	O
+unfolded	O
+protein	O
+response	O
+(	O
+UPR	O
+)	O
+,	O
+is	O
+mediated	O
+by	O
+the	O
+cis	O
+-	O
+acting	O
+ER	O
+stress	O
+response	O
+element	O
+(	O
+ERSE	O
+)	O
+in	O
+mammals	O
+.	O
+
+A	O
+Y	B-GENE
+.	I-GENE
+lipolytica	I-GENE
+Kar2p	I-GENE
+mutant	I-GENE
+was	O
+isolated	O
+that	O
+restored	O
+interaction	O
+with	O
+an	O
+Sls1p	B-GENE
+mutant	I-GENE
+,	O
+suggesting	O
+that	O
+the	O
+interaction	O
+with	O
+Sls1p	B-GENE
+could	O
+be	O
+nucleotide	O
+and	O
+/	O
+or	O
+conformation	O
+dependent	O
+.	O
+
+We	O
+have	O
+carried	O
+out	O
+a	O
+comprehensive	O
+and	O
+systematic	O
+mutagenesis	O
+of	O
+the	O
+Cse4p	B-GENE
+N	I-GENE
+terminus	I-GENE
+to	O
+analyze	O
+its	O
+function	O
+.	O
+
+The	O
+spacing	O
+of	O
+the	O
+essential	O
+N	O
+-	O
+terminal	O
+domain	O
+(	O
+END	O
+)	O
+relative	O
+to	O
+the	O
+HFD	B-GENE
+can	O
+be	O
+changed	O
+significantly	O
+without	O
+an	O
+apparent	O
+effect	O
+on	O
+Cse4p	B-GENE
+function	O
+.	O
+
+The	O
+bases	O
+of	O
+this	O
+comparison	O
+are	O
+reviewed	O
+and	O
+discussed	O
+.	O
+
+In	O
+invertebrates	O
+,	O
+Fhit	B-GENE
+is	O
+encoded	O
+as	O
+a	O
+fusion	O
+protein	O
+with	O
+Nit	B-GENE
+,	O
+a	O
+member	O
+of	O
+the	O
+nitrilase	B-GENE
+superfamily	I-GENE
+.	O
+
+The	O
+manifestations	O
+often	O
+include	O
+a	O
+moderate	O
+thrombocytopenia	O
+and	O
+,	O
+less	O
+commonly	O
+,	O
+hemolysis	O
+.	O
+
+A	O
+beta2	B-GENE
+RARE	I-GENE
+reporter	I-GENE
+construct	I-GENE
+in	O
+which	O
+the	O
+methylation	O
+-	O
+susceptible	O
+cytosines	O
+in	O
+the	O
+sense	O
+strand	O
+were	O
+replaced	O
+by	O
+thymine	O
+displayed	O
+marked	O
+loss	O
+of	O
+activity	O
+in	O
+a	O
+replicated	O
+chromatin	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Non	O
+-	O
+poliomyelitis	O
+AFP	O
+rate	O
+had	O
+increased	O
+from	O
+0	O
+.	O
+9	O
+in	O
+1997	O
+to	O
+2	O
+.	O
+8	O
+in	O
+1998	O
+.	O
+
+Consciousness	O
+is	O
+connected	O
+with	O
+attention	O
+,	O
+working	O
+memory	O
+and	O
+perception	O
+.	O
+
+Multiparity	O
+had	O
+a	O
+protective	O
+effect	O
+with	O
+0	O
+.	O
+66	O
+less	O
+risk	O
+(	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+44	O
+-	O
+0	O
+.	O
+99	O
+)	O
+.	O
+
+Picture	O
+the	O
+smell	O
+.	O
+
+Only	O
+two	O
+of	O
+27	O
+participants	O
+(	O
+7	O
+.	O
+4	O
+%	O
+)	O
+with	O
+definite	O
+POAG	O
+had	O
+been	O
+previously	O
+diagnosed	O
+and	O
+treated	O
+,	O
+and	O
+66	O
+.	O
+7	O
+%	O
+of	O
+the	O
+previously	O
+undiagnosed	O
+had	O
+IOP	O
+less	O
+than	O
+22	O
+mmHg	O
+.	O
+
+Taken	O
+together	O
+,	O
+they	O
+uphold	O
+the	O
+emerging	O
+concern	O
+that	O
+women	O
+with	O
+ER	B-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+cancers	O
+may	O
+not	O
+benefit	O
+significantly	O
+from	O
+endocrine	O
+treatment	O
+if	O
+the	O
+tumors	O
+also	O
+overexpress	O
+HER	B-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+Promoter	O
+activity	O
+was	O
+dose	O
+-	O
+dependently	O
+inhibited	O
+by	O
+cotransfection	O
+with	O
+either	O
+ras	B-GENE
+or	O
+mos	B-GENE
+oncogenes	I-GENE
+,	O
+but	O
+oncogene	O
+inhibition	O
+was	O
+reversed	O
+and	O
+the	O
+overall	O
+activity	O
+increased	O
+when	O
+cells	O
+were	O
+treated	O
+with	O
+the	O
+MAP	B-GENE
+kinase	I-GENE
+kinase	I-GENE
+(	O
+MKK	B-GENE
+)	O
+inhibitor	O
+PD98059	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+the	O
+expression	O
+of	O
+Cktsf1b1	B-GENE
+,	O
+a	O
+gene	O
+associated	O
+with	O
+early	O
+development	O
+and	O
+cell	O
+transformation	O
+,	O
+is	O
+sensitive	O
+to	O
+MKK	B-GENE
+levels	O
+and	O
+may	O
+be	O
+regulated	O
+via	O
+multiple	O
+transcription	O
+factor	O
+complexes	O
+.	O
+
+INTERVENTIONS	O
+:	O
+Subcutaneous	O
+tissue	O
+PO2	O
+and	O
+PCO2	O
+tensions	O
+were	O
+measured	O
+directly	O
+in	O
+patients	O
+with	O
+necrotising	O
+fasciitis	O
+and	O
+in	O
+healthy	O
+volunteers	O
+during	O
+normobaric	O
+and	O
+hyperbaric	O
+conditions	O
+.	O
+
+Because	O
+GH	B-GENE
+-	O
+induced	O
+Akt	B-GENE
+activation	O
+was	O
+completely	O
+inhibited	O
+in	O
+both	O
+cells	O
+by	O
+the	O
+same	O
+concentration	O
+of	O
+LY294002	O
+,	O
+these	O
+findings	O
+indicate	O
+that	O
+the	O
+wortmannin	O
+sensitivity	O
+of	O
+both	O
+the	O
+IRS	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+independent	O
+and	O
+-	O
+dependent	O
+GH	B-GENE
+-	O
+induced	O
+MAP	B-GENE
+kinase	I-GENE
+activation	O
+may	O
+reflect	O
+the	O
+activity	O
+of	O
+another	O
+wortmannin	O
+-	O
+sensitive	O
+target	O
+(	O
+s	O
+)	O
+in	O
+addition	O
+to	O
+PI3K	B-GENE
+in	O
+mediation	O
+of	O
+GH	B-GENE
+-	O
+induced	O
+MAP	B-GENE
+kinase	I-GENE
+activation	O
+in	O
+these	O
+cells	O
+.	O
+
+Insulin	B-GENE
+receptor	I-GENE
+substrate	I-GENE
+-	I-GENE
+1	I-GENE
+-	O
+mediated	O
+enhancement	O
+of	O
+growth	B-GENE
+hormone	I-GENE
+-	O
+induced	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+activation	O
+.	O
+
+Functional	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+fMRI	O
+)	O
+has	O
+been	O
+increasingly	O
+used	O
+in	O
+studying	O
+human	O
+brain	O
+function	O
+given	O
+its	O
+non	O
+-	O
+invasive	O
+feature	O
+and	O
+good	O
+spatial	O
+resolution	O
+.	O
+
+After	O
+declamping	O
+of	O
+the	O
+aorta	O
+,	O
+there	O
+were	O
+also	O
+severe	O
+edema	O
+,	O
+local	O
+fibre	O
+necrosis	O
+,	O
+and	O
+adhesion	O
+of	O
+leucocytes	O
+,	O
+whereas	O
+muscle	O
+fibre	O
+areas	O
+became	O
+3	O
+,	O
+935	O
+.	O
+18	O
+micro	O
+531	O
+microm	O
+(	O
+2	O
+)	O
+for	O
+type	O
+I	O
+and	O
+5	O
+,	O
+804	O
++	O
+/	O
+-	O
+1	O
+,	O
+075	O
+microm	O
+(	O
+2	O
+)	O
+for	O
+type	O
+II	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+increase	O
+in	O
+the	O
+RH	O
+level	O
+boosts	O
+the	O
+current	O
+values	O
+by	O
+2	O
+-	O
+3	O
+orders	O
+of	O
+magnitude	O
+;	O
+contrariwise	O
+,	O
+the	O
+voltage	O
+values	O
+rise	O
+by	O
+about	O
+three	O
+times	O
+with	O
+drop	O
+in	O
+the	O
+RH	O
+.	O
+
+Genomic	O
+libraries	O
+were	O
+stored	O
+as	O
+frozen	O
+cultures	O
+in	O
+a	O
+96	O
+-	O
+well	O
+format	O
+,	O
+each	O
+well	O
+containing	O
+approximately	O
+300	O
+-	O
+600	O
+colonies	O
+(	O
+12	O
+plates	O
+for	O
+small	O
+library	O
+,	O
+four	O
+for	O
+medium	O
+-	O
+size	O
+library	O
+and	O
+four	O
+for	O
+large	O
+library	O
+)	O
+.	O
+
+In	O
+several	O
+cell	O
+lines	O
+,	O
+mTOR	B-GENE
+or	O
+its	O
+downstream	O
+targets	O
+can	O
+be	O
+regulated	O
+by	O
+phosphatidylinositol	B-GENE
+(	I-GENE
+PI	I-GENE
+)	I-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+;	O
+protein	B-GENE
+kinases	I-GENE
+A	I-GENE
+,	I-GENE
+B	I-GENE
+,	I-GENE
+and	I-GENE
+C	I-GENE
+;	O
+heterotrimeric	B-GENE
+G	I-GENE
+-	I-GENE
+proteins	I-GENE
+;	O
+a	O
+PD98059	O
+-	O
+sensitive	O
+kinase	O
+or	O
+calcium	O
+;	O
+as	O
+well	O
+as	O
+by	O
+amino	O
+acids	O
+.	O
+
+The	O
+importance	O
+of	O
+this	O
+new	O
+epidemiological	O
+profile	O
+of	O
+schistosomiasis	O
+in	O
+the	O
+State	O
+of	O
+Pernambuco	O
+relies	O
+on	O
+the	O
+fact	O
+that	O
+it	O
+can	O
+be	O
+related	O
+with	O
+the	O
+drastic	O
+human	O
+interference	O
+on	O
+the	O
+environment	O
+.	O
+
+RESULTS	O
+:	O
+No	O
+significant	O
+deformation	O
+in	O
+vertebral	O
+artery	O
+flow	O
+was	O
+noted	O
+in	O
+the	O
+flexion	O
+-	O
+distraction	O
+Stage	O
+I	O
+injuries	O
+within	O
+the	O
+physiologic	O
+range	O
+of	O
+cervical	O
+flexion	O
+.	O
+
+We	O
+screened	O
+a	O
+K562	O
+cDNA	O
+library	O
+and	O
+identified	O
+novel	O
+transcripts	O
+,	O
+MZF1B	B-GENE
+and	O
+MZF1C	B-GENE
+.	O
+
+The	O
+human	O
+cDNA	O
+clone	O
+NFBD1	O
+(	O
+previously	O
+designated	O
+KIAA0170	O
+)	O
+encodes	O
+a	O
+novel	O
+protein	O
+(	O
+2089	O
+amino	O
+acids	O
+in	O
+length	O
+;	O
+calculated	O
+molecular	O
+mass	O
+226	O
+,	O
+440	O
+D	O
+)	O
+with	O
+possible	O
+BRCT	B-GENE
+domains	I-GENE
+at	O
+its	O
+carboxy	O
+terminus	O
+(	O
+amino	O
+acid	O
+residues	O
+1894	O
+-	O
+2089	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+Neither	O
+basal	O
+FSH	B-GENE
+level	O
+nor	O
+stimulated	O
+FSH	B-GENE
+level	O
+alone	O
+were	O
+statistically	O
+significant	O
+predictors	O
+of	O
+IVF	O
+success	O
+;	O
+however	O
+,	O
+no	O
+patient	O
+with	O
+a	O
+day	O
+3	O
+FSH	B-GENE
+level	O
+>	O
+11	O
+.	O
+1	O
+mIU	O
+/	O
+ml	O
+or	O
+a	O
+stimulated	O
+day	O
+10	O
+FSH	B-GENE
+level	O
+>	O
+13	O
+.	O
+5	O
+mIU	O
+/	O
+ml	O
+conceived	O
+and	O
+carried	O
+a	O
+pregnancy	O
+.	O
+
+Parathyroid	B-GENE
+hormone	I-GENE
+regulation	O
+of	O
+bone	B-GENE
+sialoprotein	I-GENE
+(	O
+BSP	B-GENE
+)	O
+gene	O
+transcription	O
+is	O
+mediated	O
+through	O
+a	O
+pituitary	B-GENE
+-	I-GENE
+specific	I-GENE
+transcription	I-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+Pit	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+motif	O
+in	O
+the	O
+rat	B-GENE
+BSP	I-GENE
+gene	I-GENE
+promoter	I-GENE
+.	O
+
+Recent	O
+target	O
+BP	O
+goals	O
+promulgated	O
+by	O
+the	O
+Sixth	O
+Report	O
+from	O
+the	O
+Joint	O
+National	O
+Committee	O
+(	O
+JNC	O
+VI	O
+)	O
+are	O
+based	O
+on	O
+the	O
+premise	O
+that	O
+the	O
+intensity	O
+of	O
+treatment	O
+directly	O
+corresponds	O
+to	O
+the	O
+magnitude	O
+of	O
+pretreatment	O
+risk	O
+.	O
+
+Linking	O
+continuous	O
+community	O
+-	O
+based	O
+morbidity	O
+recording	O
+of	O
+influenza	O
+-	O
+like	O
+illness	O
+(	O
+ILI	O
+)	O
+with	O
+virological	O
+sampling	O
+has	O
+consistently	O
+proved	O
+its	O
+value	O
+as	O
+one	O
+of	O
+the	O
+earliest	O
+indicators	O
+of	O
+circulating	O
+influenza	O
+activity	O
+.	O
+
+These	O
+include	O
+NPF	O
+repeats	O
+,	O
+a	O
+leucine	O
+heptad	O
+repeat	O
+enriched	O
+in	O
+charged	O
+residues	O
+,	O
+and	O
+a	O
+proline	O
+-	O
+rich	O
+SH3	B-GENE
+-	I-GENE
+like	I-GENE
+and	O
+/	O
+or	O
+WW	O
+domain	O
+-	O
+binding	O
+site	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+domain	O
+,	O
+which	O
+is	O
+followed	O
+by	O
+a	O
+membrane	O
+core	O
+containing	O
+four	O
+putative	O
+transmembrane	O
+spans	O
+and	O
+three	O
+amphiphilic	O
+segments	O
+that	O
+are	O
+the	O
+most	O
+highly	O
+conserved	O
+structural	O
+elements	O
+.	O
+
+We	O
+show	O
+here	O
+that	O
+this	O
+difference	O
+is	O
+due	O
+to	O
+the	O
+presence	O
+of	O
+a	O
+Mot3	B-GENE
+binding	I-GENE
+site	I-GENE
+in	O
+OpA	B-GENE
+.	O
+
+The	O
+article	O
+deals	O
+with	O
+the	O
+diagnosing	O
+and	O
+correction	O
+of	O
+reversible	O
+ischemia	O
+of	O
+the	O
+intestine	O
+.	O
+
+Functional	O
+recognition	O
+of	O
+5	O
+'	O
+splice	O
+site	O
+by	O
+U4	B-GENE
+/	O
+U6	B-GENE
+.	O
+U5	B-GENE
+tri	O
+-	O
+snRNP	O
+defines	O
+a	O
+novel	O
+ATP	O
+-	O
+dependent	O
+step	O
+in	O
+early	O
+spliceosome	O
+assembly	O
+.	O
+
+As	O
+control	O
+,	O
+the	O
+cells	O
+were	O
+transfected	O
+with	O
+DNA	O
+mixtures	O
+containing	O
+vector	O
+mU6	O
+-	O
+C1	O
+or	O
+mU6	O
+-	O
+C2	O
+.	O
+
+In	O
+this	O
+regard	O
+,	O
+we	O
+have	O
+recently	O
+observed	O
+that	O
+a	O
+constitutively	O
+active	O
+G	B-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+receptor	I-GENE
+(	O
+GPCR	B-GENE
+)	O
+encoded	O
+by	O
+the	O
+Kaposi	O
+'	O
+s	O
+sarcoma	O
+-	O
+associated	O
+herpes	O
+virus	O
+(	O
+KSHV	O
+)	O
+/	O
+human	O
+herpes	O
+virus	O
+8	O
+is	O
+oncogenic	O
+and	O
+stimulates	O
+angiogenesis	O
+by	O
+increasing	O
+the	O
+secretion	O
+of	O
+vascular	B-GENE
+endothelial	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+VEGF	B-GENE
+)	O
+,	O
+which	O
+is	O
+a	O
+key	O
+angiogenic	O
+stimulator	O
+and	O
+a	O
+critical	O
+mitogen	O
+for	O
+the	O
+development	O
+of	O
+Kaposi	O
+'	O
+s	O
+sarcoma	O
+.	O
+
+No	O
+specific	O
+subgroup	O
+of	O
+clients	O
+benefited	O
+more	O
+from	O
+URD	O
+,	O
+although	O
+a	O
+prospective	O
+study	O
+employing	O
+random	O
+assignment	O
+might	O
+be	O
+more	O
+successful	O
+in	O
+identifying	O
+such	O
+a	O
+group	O
+.	O
+
+In	O
+the	O
+lattice	O
+,	O
+23	O
+%	O
+of	O
+the	O
+sites	O
+are	O
+occupied	O
+,	O
+95	O
+%	O
+of	O
+the	O
+atoms	O
+are	O
+in	O
+the	O
+lowest	O
+energy	O
+magnetic	O
+sublevel	O
+,	O
+and	O
+37	O
+%	O
+are	O
+in	O
+the	O
+lowest	O
+3D	O
+vibrational	O
+state	O
+.	O
+
+Coexisting	O
+vertical	O
+and	O
+horizontal	O
+one	O
+and	O
+a	O
+half	O
+syndromes	O
+.	O
+
+As	O
+in	O
+the	O
+other	O
+three	O
+members	O
+whose	O
+gene	O
+expression	O
+is	O
+altered	O
+during	O
+tumorigenesis	O
+,	O
+PI12	B-GENE
+expression	O
+was	O
+found	O
+to	O
+be	O
+down	O
+-	O
+regulated	O
+in	O
+tumor	O
+brain	O
+tissues	O
+and	O
+in	O
+two	O
+brain	O
+cancer	O
+cell	O
+lines	O
+:	O
+U	O
+-	O
+87	O
+MG	O
+and	O
+H4	O
+.	O
+
+This	O
+slope	O
+was	O
+further	O
+significantly	O
+decreased	O
+at	O
+5	O
+min	O
+ischemia	O
+(	O
+-	O
+26	O
+.	O
+5	O
++	O
+/	O
+-	O
+8	O
+.	O
+8	O
+microm	O
+/	O
+mmHg	O
+)	O
+but	O
+returned	O
+toward	O
+control	O
+values	O
+in	O
+short	O
+-	O
+term	O
+hibernating	O
+myocardium	O
+at	O
+90	O
+min	O
+ischemia	O
+(	O
+-	O
+17	O
+.	O
+2	O
++	O
+/	O
+-	O
+6	O
+.	O
+6	O
+microm	O
+/	O
+mmHg	O
+)	O
+.	O
+
+Whereas	O
+both	O
+MAP	O
+and	O
+MSNA	O
+increase	O
+during	O
+SHG	O
+,	O
+the	O
+transition	O
+from	O
+SHG	O
+to	O
+PHI	O
+is	O
+characterized	O
+by	O
+a	O
+transient	O
+reduction	O
+in	O
+MAP	O
+but	O
+sustained	O
+elevation	O
+in	O
+MSNA	O
+,	O
+facilitating	O
+separation	O
+of	O
+these	O
+factors	O
+in	O
+vivo	O
+.	O
+
+We	O
+have	O
+recently	O
+discovered	O
+that	O
+CCAAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+-	I-GENE
+beta	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+-	I-GENE
+beta	I-GENE
+)	O
+induces	O
+gene	O
+transcription	O
+through	O
+a	O
+novel	O
+IFN	B-GENE
+response	I-GENE
+element	I-GENE
+called	O
+the	O
+gamma	B-GENE
+-	I-GENE
+IFN	I-GENE
+-	I-GENE
+activated	I-GENE
+transcriptional	I-GENE
+element	I-GENE
+
+Northern	O
+blot	O
+analysis	O
+demonstrated	O
+that	O
+the	O
+STORP	B-GENE
+gene	I-GENE
+has	O
+a	O
+ubiquitous	O
+pattern	O
+of	O
+expression	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+PML	B-GENE
+gene	I-GENE
+.	O
+
+In	O
+the	O
+TLE	O
+patients	O
+the	O
+NAA	O
+:	O
+Cr	O
+ratios	O
+were	O
+reduced	O
+in	O
+the	O
+seizure	O
+focus	O
+,	O
+while	O
+in	O
+the	O
+FLE	O
+patients	O
+they	O
+were	O
+not	O
+always	O
+reduced	O
+in	O
+the	O
+seizure	O
+focus	O
+.	O
+
+The	O
+psychologic	O
+factors	O
+associated	O
+wth	O
+serious	O
+illness	O
+,	O
+terminal	O
+prognoses	O
+,	O
+and	O
+dying	O
+complicate	O
+the	O
+scenario	O
+even	O
+more	O
+as	O
+compared	O
+with	O
+that	O
+of	O
+nonmalignant	O
+pain	O
+.	O
+
+However	O
+,	O
+if	O
+the	O
+spatial	O
+resolution	O
+is	O
+not	O
+critical	O
+and	O
+interest	O
+is	O
+to	O
+compare	O
+a	O
+pathologic	O
+area	O
+with	O
+a	O
+contralateral	O
+VOI	O
+,	O
+then	O
+the	O
+acquisition	O
+of	O
+two	O
+single	O
+-	O
+voxel	O
+spectra	O
+may	O
+be	O
+preferred	O
+.	O
+
+Quantitative	O
+evaluation	O
+of	O
+magneto	O
+-	O
+optical	O
+parameters	O
+is	O
+necessary	O
+in	O
+order	O
+to	O
+apply	O
+scanning	O
+near	O
+-	O
+field	O
+optical	O
+microscope	O
+(	O
+SNOM	O
+)	O
+technology	O
+to	O
+the	O
+study	O
+of	O
+magnetism	O
+on	O
+the	O
+mesoscopic	O
+scale	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+amplitude	O
+of	O
+the	O
+cortical	O
+evoked	O
+potentials	O
+(	O
+amplitude	O
+of	O
+the	O
+N2	O
+/	O
+P2	O
+peak	O
+)	O
+increased	O
+from	O
+5	O
+.	O
+1	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+microV	O
+at	O
+5	O
+mA	O
+to	O
+16	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+microV	O
+at	O
+20	O
+mA	O
+.	O
+
+LMP	B-GENE
+-	I-GENE
+1	I-GENE
+is	O
+targeted	O
+to	O
+the	O
+plasma	O
+membrane	O
+,	O
+where	O
+it	O
+binds	O
+TRAF	B-GENE
+,	O
+TRADD	B-GENE
+,	O
+and	O
+JAK	B-GENE
+molecules	I-GENE
+to	O
+activate	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+-	O
+,	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+,	O
+and	O
+STAT	B-GENE
+-	O
+dependent	O
+pathways	O
+as	O
+does	O
+CD40	B-GENE
+.	O
+
+Identification	O
+of	O
+an	O
+enhancer	O
+and	O
+an	O
+alternative	O
+promoter	O
+in	O
+the	O
+first	O
+intron	O
+of	O
+the	O
+alpha	B-GENE
+-	I-GENE
+fetoprotein	I-GENE
+gene	I-GENE
+.	O
+
+Studying	O
+intracellular	O
+signaling	O
+pathways	O
+,	O
+which	O
+may	O
+be	O
+involved	O
+in	O
+malignant	O
+transformation	O
+of	O
+Ret	B-GENE
+-	I-GENE
+9bp	I-GENE
+expressing	O
+NIH3T3	O
+cells	O
+,	O
+we	O
+could	O
+demonstrate	O
+Ret	B-GENE
+-	I-GENE
+9bp	I-GENE
+dependent	O
+phosphorylation	O
+of	O
+insulin	B-GENE
+receptor	I-GENE
+substrate	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+IRS	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+with	O
+consecutive	O
+activation	O
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+(	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+)	O
+and	O
+protein	B-GENE
+kinase	I-GENE
+B	I-GENE
+(	O
+PKB	B-GENE
+/	O
+AKT	B-GENE
+)	O
+.	O
+
+METHODS	O
+:	O
+In	O
+the	O
+current	O
+study	O
+the	O
+authors	O
+reported	O
+on	O
+PPB	O
+cases	O
+from	O
+a	O
+national	O
+retrospective	O
+search	O
+performed	O
+in	O
+18	O
+Italian	O
+Associations	O
+for	O
+Pediatric	O
+Hematology	O
+and	O
+Oncology	O
+centers	O
+.	O
+
+Phylogenetic	O
+analysis	O
+showed	O
+that	O
+the	O
+ToLCV	O
+isolates	O
+from	O
+Bangalore	O
+constitute	O
+a	O
+group	O
+of	O
+viruses	O
+separated	O
+from	O
+those	O
+of	O
+Northern	O
+India	O
+.	O
+
+Mutating	O
+the	O
+Fcp1p	B-GENE
+-	O
+binding	O
+motif	O
+KEFGK	O
+in	O
+the	O
+RAP74	B-GENE
+(	O
+Tfg1p	B-GENE
+)	O
+subunit	O
+of	O
+TFIIF	B-GENE
+to	O
+EEFGE	O
+led	O
+to	O
+both	O
+synthetic	O
+phenotypes	O
+in	O
+certain	O
+fcp1	B-GENE
+tfg1	B-GENE
+double	O
+mutants	O
+and	O
+a	O
+reduced	O
+ability	O
+of	O
+Fcp1p	B-GENE
+to	O
+activate	O
+transcription	O
+when	O
+it	O
+is	O
+artificially	O
+tethered	O
+to	O
+a	O
+promoter	O
+.	O
+
+Deletion	O
+of	O
+an	O
+intergenic	O
+DNA	O
+-	O
+binding	O
+site	O
+for	O
+this	O
+complex	O
+from	O
+a	O
+human	B-GENE
+beta	I-GENE
+-	I-GENE
+globin	I-GENE
+locus	I-GENE
+construct	I-GENE
+results	O
+in	O
+delayed	O
+human	B-GENE
+gamma	I-GENE
+-	I-GENE
+to	I-GENE
+beta	I-GENE
+-	I-GENE
+globin	I-GENE
+switching	O
+in	O
+transgenic	O
+mice	O
+,	O
+suggesting	O
+that	O
+the	O
+PYR	B-GENE
+complex	I-GENE
+acts	O
+to	O
+facilitate	O
+the	O
+switch	O
+.	O
+
+The	O
+product	O
+of	O
+rat	B-GENE
+gene	I-GENE
+33	I-GENE
+was	O
+identified	O
+as	O
+an	O
+ErbB	B-GENE
+-	I-GENE
+2	I-GENE
+-	I-GENE
+interacting	I-GENE
+protein	I-GENE
+in	O
+a	O
+two	O
+-	O
+hybrid	O
+screen	O
+employing	O
+the	O
+ErbB	B-GENE
+-	I-GENE
+2	I-GENE
+juxtamembrane	I-GENE
+and	I-GENE
+kinase	I-GENE
+domains	I-GENE
+as	O
+bait	O
+.	O
+
+Studies	O
+suggest	O
+that	O
+the	O
+DGOR	O
+without	O
+acid	O
+reflux	O
+may	O
+result	O
+in	O
+symptoms	O
+but	O
+unless	O
+acid	O
+reflux	O
+is	O
+present	O
+simultaneously	O
+,	O
+it	O
+does	O
+not	O
+cause	O
+oesophagitis	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+evaluate	O
+the	O
+relationship	O
+between	O
+blood	O
+flow	O
+in	O
+the	O
+tumor	O
+assessed	O
+by	O
+color	O
+Doppler	O
+ultrasound	O
+,	O
+microvessel	O
+density	O
+,	O
+and	O
+vascular	B-GENE
+endothelial	I-GENE
+growth	I-GENE
+factor	I-GENE
+levels	O
+in	O
+endometrial	O
+carcinoma	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+Ras	B-GENE
+-	O
+and	O
+Raf	B-GENE
+-	O
+independent	O
+ERK	B-GENE
+MAPK	O
+activation	O
+maintains	O
+cell	O
+viability	O
+following	O
+heat	O
+shock	O
+.	O
+
+Three	O
+cDNAs	O
+encoding	O
+basic	B-GENE
+leucine	I-GENE
+zipper	I-GENE
+(	I-GENE
+bZIP	I-GENE
+)	I-GENE
+-	I-GENE
+type	I-GENE
+ABRE	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+were	O
+isolated	O
+by	O
+using	O
+the	O
+yeast	O
+one	O
+-	O
+hybrid	O
+system	O
+and	O
+were	O
+designated	O
+AREB1	B-GENE
+,	O
+AREB2	B-GENE
+,	O
+and	O
+AREB3	B-GENE
+(	O
+ABA	B-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+binding	I-GENE
+protein	I-GENE
+)	O
+.	O
+
+Recombinant	O
+AROM	B-GENE
+-	O
+p64	B-GENE
+displayed	O
+high	O
+binding	O
+to	O
+single	O
+-	O
+stranded	O
+DNA	O
+and	O
+poly	O
+(	O
+A	O
+)	O
+homopolymers	O
+suggesting	O
+that	O
+this	O
+protein	O
+could	O
+play	O
+a	O
+role	O
+in	O
+mRNA	O
+maturation	O
+/	O
+metabolism	O
+.	O
+
+The	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+fer	B-GENE
+associates	O
+with	O
+signaling	O
+complexes	O
+containing	O
+insulin	B-GENE
+receptor	I-GENE
+substrate	I-GENE
+-	I-GENE
+1	I-GENE
+and	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+.	O
+
+In	O
+the	O
+PMR	O
+target	O
+area	O
+but	O
+not	O
+in	O
+the	O
+nontreated	O
+area	O
+an	O
+improvement	O
+in	O
+regional	O
+myocardial	O
+flow	O
+reserve	O
+occurs	O
+in	O
+wall	O
+segments	O
+with	O
+initially	O
+severely	O
+or	O
+moderately	O
+reduced	O
+stress	O
+perfusion	O
+.	O
+
+Analysis	O
+of	O
+intron	O
+/	O
+exon	O
+boundaries	O
+of	O
+the	O
+genomic	O
+BAC	O
+clones	O
+demonstrate	O
+that	O
+junctin	B-GENE
+,	O
+junctate	B-GENE
+,	O
+and	O
+aspartyl	B-GENE
+beta	I-GENE
+-	I-GENE
+hydroxylase	I-GENE
+result	O
+from	O
+alternative	O
+splicing	O
+of	O
+the	O
+same	O
+gene	O
+.	O
+
+The	O
+growth	B-GENE
+factor	I-GENE
+receptor	I-GENE
+-	I-GENE
+bound	I-GENE
+protein	I-GENE
+2	I-GENE
+(	O
+Grb2	B-GENE
+)	O
+adaptor	O
+when	O
+complexed	O
+with	O
+Sos	B-GENE
+(	O
+Son	B-GENE
+of	I-GENE
+sevenless	I-GENE
+)	O
+,	O
+the	O
+exchange	O
+factor	O
+of	O
+Ras	B-GENE
+,	O
+conveys	O
+the	O
+signal	O
+induced	O
+by	O
+tyrosine	B-GENE
+kinase	I-GENE
+-	I-GENE
+activated	I-GENE
+receptor	I-GENE
+to	O
+Ras	B-GENE
+by	O
+recruiting	O
+Sos	B-GENE
+to	O
+the	O
+membrane	O
+,	O
+allowing	O
+activation	O
+of	O
+Ras	B-GENE
+.	O
+
+Mutations	O
+in	O
+genes	O
+encoding	O
+PR65	B-GENE
+/	I-GENE
+A	I-GENE
+subunits	I-GENE
+have	O
+been	O
+identified	O
+in	O
+several	O
+different	O
+human	O
+cancers	O
+and	O
+the	O
+PP2A	B-GENE
+inhibitor	O
+,	O
+termed	O
+fostriecin	O
+,	O
+is	O
+being	O
+tested	O
+as	O
+an	O
+anticancer	O
+drug	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+a	O
+segment	O
+of	O
+dxr	B-GENE
+was	O
+amplified	O
+from	O
+Synechococcus	O
+leopoliensis	O
+SAUG	O
+1402	O
+-	O
+1	O
+DNA	O
+via	O
+PCR	O
+using	O
+oligonucleotides	O
+for	O
+conserved	O
+regions	O
+.	O
+
+Perceptual	O
+learning	O
+for	O
+a	O
+pattern	O
+discrimination	O
+task	O
+.	O
+
+While	O
+this	O
+Saccharomyces	O
+cerevisiae	O
+SIN4	B-GENE
+gene	I-GENE
+product	I-GENE
+is	O
+a	O
+component	O
+of	O
+a	O
+mediator	O
+complex	O
+associated	O
+with	O
+RNA	B-GENE
+polymerase	I-GENE
+II	I-GENE
+,	O
+various	O
+studies	O
+suggest	O
+the	O
+involvement	O
+of	O
+Sin4	B-GENE
+in	O
+the	O
+alteration	O
+of	O
+higher	O
+-	O
+order	O
+chromatin	O
+structure	O
+.	O
+
+Src	B-GENE
+activation	O
+induced	O
+by	O
+FGF1	B-GENE
+was	O
+blocked	O
+by	O
+the	O
+SH2	B-GENE
+domain	I-GENE
+of	O
+Src	B-GENE
+and	O
+PP2	B-GENE
+,	O
+a	O
+specific	O
+inhibitor	O
+of	O
+Src	B-GENE
+.	O
+
+The	O
+use	O
+of	O
+the	O
+PLCgamma	B-GENE
+inhibitory	I-GENE
+peptide	I-GENE
+,	O
+neomycin	O
+and	O
+the	O
+calcium	O
+chelator	O
+BAPTA	O
+-	O
+AM	O
+on	O
+oocytes	O
+expressing	O
+FGFR1	B-GENE
+or	O
+the	O
+stimulation	O
+by	O
+PDGF	B-GENE
+-	I-GENE
+BB	I-GENE
+of	O
+oocytes	O
+expressing	O
+PDGFR	B-GENE
+-	O
+FGFR1	B-GENE
+mutated	O
+on	O
+the	O
+PLCgamma	B-GENE
+binding	I-GENE
+site	I-GENE
+,	O
+prevented	O
+GVBD	O
+and	O
+ERK2	B-GENE
+phosphorylation	O
+.	O
+
+Multiple	O
+transcription	O
+start	O
+sites	O
+were	O
+revealed	O
+by	O
+primer	O
+extension	O
+analysis	O
+of	O
+the	O
+mouse	O
+gene	O
+,	O
+and	O
+transfection	O
+constructs	O
+containing	O
+the	O
+prospective	O
+promoter	O
+generated	O
+transcriptional	O
+activity	O
+comparable	O
+to	O
+that	O
+of	O
+the	O
+SV40	B-GENE
+promoter	I-GENE
+.	O
+
+To	O
+determine	O
+whether	O
+interaction	O
+of	O
+arsenite	O
+with	O
+the	O
+hormone	O
+-	O
+binding	O
+domain	O
+results	O
+in	O
+receptor	O
+activation	O
+,	O
+COS	O
+-	O
+1	O
+cells	O
+were	O
+transiently	O
+cotransfected	O
+with	O
+the	O
+chimeric	B-GENE
+receptors	I-GENE
+GAL	I-GENE
+-	I-GENE
+ER	I-GENE
+,	O
+which	O
+contains	O
+the	O
+hormone	O
+-	O
+binding	O
+domain	O
+of	O
+ERalpha	B-GENE
+and	O
+the	O
+DNA	O
+-	O
+binding	O
+domain	O
+of	O
+the	O
+transcription	O
+factor	O
+GAL4	B-GENE
+,	O
+and	O
+a	O
+GAL4	B-GENE
+-	O
+responsive	O
+CAT	B-GENE
+reporter	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+mean	O
+day	O
+of	O
+diagnosis	O
+of	O
+periventricular	O
+echodensities	O
+was	O
+3	O
++	O
+/	O
+-	O
+2	O
+days	O
+(	O
+range	O
+1	O
+-	O
+11	O
+days	O
+)	O
+,	O
+and	O
+of	O
+cystic	O
+PVL	O
+21	O
++	O
+/	O
+-	O
+8	O
+days	O
+(	O
+range	O
+2	O
+-	O
+47	O
+days	O
+)	O
+.	O
+
+The	O
+LAMMER	B-GENE
+protein	O
+kinase	O
+encoded	O
+by	O
+the	O
+Doa	B-GENE
+locus	I-GENE
+of	O
+Drosophila	O
+is	O
+required	O
+in	O
+both	O
+somatic	O
+and	O
+germline	O
+cells	O
+and	O
+is	O
+expressed	O
+as	O
+both	O
+nuclear	O
+and	O
+cytoplasmic	O
+isoforms	O
+throughout	O
+development	O
+.	O
+
+We	O
+have	O
+mutated	O
+to	O
+cysteine	O
+,	O
+one	O
+at	O
+a	O
+time	O
+,	O
+21	O
+consecutive	O
+residues	O
+in	O
+the	O
+fourth	O
+TMS	O
+(	O
+TM4	O
+)	O
+.	O
+
+(	O
+1995	O
+)	O
+J	O
+.	O
+
+HYPOTHESIS	O
+:	O
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+the	O
+oxidative	O
+susceptibility	O
+of	O
+apolipoprotein	B-GENE
+B	I-GENE
+-	I-GENE
+containing	I-GENE
+lipoproteins	I-GENE
+and	O
+antioxidant	O
+status	O
+in	O
+patients	O
+with	O
+acute	O
+coronary	O
+syndromes	O
+and	O
+chronic	O
+stable	O
+angina	O
+pectoris	O
+.	O
+
+In	O
+group	O
+B	O
+37	O
+MBq	O
+in	O
+150	O
+microL	O
+of	O
+99mTc	O
+-	O
+HSA	O
+nanocolloid	O
+was	O
+additionally	O
+injected	O
+intradermally	O
+18	O
+h	O
+before	O
+surgery	O
+(	O
+3	O
+-	O
+6	O
+aliquots	O
+injected	O
+perilesionally	O
+)	O
+.	O
+
+Post	O
+-	O
+operative	O
+functional	O
+outcome	O
+is	O
+related	O
+to	O
+pre	O
+-	O
+operative	O
+functional	O
+status	O
+.	O
+
+We	O
+cloned	O
+a	O
+DNA	O
+fragment	O
+encoding	O
+the	O
+N	O
+-	O
+terminal	O
+part	O
+of	O
+a	O
+protein	O
+with	O
+significant	O
+similarity	O
+to	O
+members	O
+of	O
+the	O
+LysR	B-GENE
+family	I-GENE
+of	I-GENE
+transcriptional	I-GENE
+regulators	I-GENE
+(	O
+LTTRs	B-GENE
+)	O
+.	O
+
+AGO1	B-GENE
+is	O
+similar	O
+to	O
+QDE	B-GENE
+-	I-GENE
+2	I-GENE
+required	O
+for	O
+quelling	O
+and	O
+RDE	B-GENE
+-	I-GENE
+1	I-GENE
+required	O
+for	O
+RNAi	O
+.	O
+
+We	O
+could	O
+demonstrate	O
+the	O
+involvement	O
+of	O
+cAMP	B-GENE
+-	I-GENE
+dependent	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+PKA	B-GENE
+)	O
+in	O
+the	O
+phosphorylation	O
+of	O
+CDC25Mm	B-GENE
+in	O
+fibroblasts	O
+overexpressing	O
+this	O
+RasGEF	B-GENE
+as	O
+well	O
+as	O
+in	O
+mouse	O
+brain	O
+synaptosomal	O
+membranes	O
+.	O
+
+We	O
+find	O
+that	O
+3T1	O
+-	O
+3T2	O
+mixing	O
+has	O
+a	O
+pronounced	O
+effect	O
+on	O
+the	O
+line	O
+shape	O
+and	O
+radiative	O
+decay	O
+rate	O
+of	O
+emission	O
+from	O
+the	O
+3T2	O
+state	O
+and	O
+that	O
+the	O
+extent	O
+of	O
+mixing	O
+depends	O
+critically	O
+on	O
+the	O
+magnitude	O
+of	O
+nontetrahedral	O
+distortions	O
+.	O
+
+A	O
+total	O
+of	O
+576	O
+1	O
+-	O
+day	O
+-	O
+old	O
+Ross	O
+broiler	O
+chicks	O
+were	O
+housed	O
+in	O
+six	O
+treatment	O
+groups	O
+[	O
+six	O
+replicates	O
+of	O
+16	O
+each	O
+;	O
+control	O
+,	O
+CLI	O
+(	O
+15	O
+g	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+diet	O
+)	O
+,	O
+50	O
+parts	O
+per	O
+billion	O
+(	O
+ppb	O
+)	O
+AF	B-GENE
+,	O
+50	O
+ppb	O
+AF	B-GENE
+plus	O
+CLI	O
+,	O
+100	O
+ppb	O
+AF	B-GENE
+,	O
+100	O
+ppb	O
+AF	B-GENE
+plus	O
+CLI	O
+]	O
+for	O
+42	O
+days	O
+.	O
+
+The	O
+cost	O
+per	O
+test	O
+is	O
+less	O
+than	O
+those	O
+for	O
+CC	O
+,	O
+kEIA	O
+and	O
+PACE2	O
+.	O
+
+Concurrently	O
+,	O
+we	O
+monitored	O
+weather	O
+conditions	O
+and	O
+used	O
+time	O
+-	O
+activity	O
+budget	O
+data	O
+of	O
+free	O
+-	O
+living	O
+birds	O
+and	O
+laboratory	O
+data	O
+on	O
+resting	O
+metabolic	O
+rate	O
+to	O
+construct	O
+time	O
+-	O
+activity	O
+laboratory	O
+(	O
+TAL	O
+)	O
+estimates	O
+of	O
+daily	O
+energy	O
+expenditure	O
+(	O
+DEE	O
+)	O
+and	O
+to	O
+partition	O
+the	O
+verdins	O
+'	O
+energy	O
+budget	O
+into	O
+thermoregulatory	O
+,	O
+activity	O
+and	O
+basal	O
+components	O
+.	O
+
+L	O
+/	O
+H	O
+>	O
+0	O
+.	O
+61	O
+(	O
+chi	O
+(	O
+2	O
+)	O
+=	O
+10	O
+.	O
+8	O
+;	O
+P	O
+:	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+a	O
+restrictive	O
+filling	O
+pattern	O
+(	O
+chi	O
+(	O
+2	O
+)	O
+=	O
+3	O
+.	O
+6	O
+;	O
+P	O
+:	O
+<	O
+0	O
+.	O
+05	O
+)	O
+were	O
+independent	O
+predictors	O
+of	O
+events	O
+.	O
+
+The	O
+high	O
+selectivity	O
+of	O
+arrestins	B-GENE
+for	O
+this	O
+particular	O
+functional	O
+form	O
+of	O
+receptor	O
+ensures	O
+their	O
+timely	O
+binding	O
+and	O
+dissociation	O
+.	O
+
+When	O
+cotransfected	O
+in	O
+fibroblasts	O
+with	O
+a	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+alpha	I-GENE
+expression	O
+vector	O
+,	O
+reporter	O
+gene	O
+expression	O
+increased	O
+3	O
+-	O
+fold	O
+only	O
+in	O
+the	O
+wild	O
+-	O
+type	O
+constructs	O
+.	O
+
+Expression	O
+of	O
+a	O
+dominant	B-GENE
+negative	I-GENE
+Smad2	I-GENE
+significantly	O
+reduces	O
+the	O
+level	O
+of	O
+luciferase	B-GENE
+reporter	I-GENE
+activity	O
+induced	O
+by	O
+nodal	O
+treatment	O
+.	O
+
+Normal	O
+alpha1	B-GENE
+(	I-GENE
+I	I-GENE
+)	I-GENE
+collagen	I-GENE
+mRNA	I-GENE
+showed	O
+no	O
+significant	O
+reduction	O
+when	O
+AR	O
+or	O
+IR	O
+was	O
+expressed	O
+from	O
+the	O
+pHbetaAPr	O
+-	O
+1	O
+-	O
+neo	O
+vector	O
+and	O
+a	O
+small	O
+(	O
+10	O
+-	O
+20	O
+%	O
+)	O
+but	O
+significant	O
+reduction	O
+when	O
+either	O
+ribozyme	O
+was	O
+expressed	O
+from	O
+the	O
+pCI	O
+.	O
+neo	O
+vector	O
+.	O
+
+Nature	O
+398	O
+,	O
+828	O
+-	O
+830	O
+)	O
+that	O
+the	O
+amino	O
+acid	O
+sequences	O
+of	O
+peptide	O
+fragments	O
+obtained	O
+from	O
+a	O
+polypeptide	O
+found	O
+in	O
+a	O
+complex	O
+of	O
+proteins	O
+that	O
+alters	O
+chromatin	O
+structure	O
+(	O
+ARC	B-GENE
+)	O
+are	O
+identical	O
+to	O
+portions	O
+of	O
+the	O
+deduced	O
+open	O
+reading	O
+frame	O
+of	O
+TIG	B-GENE
+-	I-GENE
+1	I-GENE
+mRNA	I-GENE
+.	O
+
+Abnormalities	O
+of	O
+plasma	B-GENE
+cholecystokinin	I-GENE
+were	O
+observed	O
+only	O
+in	O
+patients	O
+with	O
+delayed	O
+gastric	O
+emptying	O
+.	O
+
+5	O
+(	O
+Sunset	O
+Yellow	O
+FCF	O
+)	O
+were	O
+determined	O
+using	O
+liquid	O
+chromatography	O
+/	O
+mass	O
+spectrometry	O
+(	O
+LC	O
+/	O
+MS	O
+)	O
+with	O
+electrospray	O
+ionization	O
+.	O
+
+Cam	B-GENE
+kinase	I-GENE
+II	I-GENE
+induces	O
+in	O
+vivo	O
+phosphorylation	O
+of	O
+Smad2	B-GENE
+and	O
+Smad4	B-GENE
+and	O
+,	O
+to	O
+a	O
+lesser	O
+extent	O
+,	O
+Smad3	B-GENE
+.	O
+
+This	O
+interaction	O
+inhibits	O
+the	O
+histone	B-GENE
+acetyltransferase	I-GENE
+activity	O
+of	O
+p300	B-GENE
+,	O
+resulting	O
+in	O
+drastic	O
+reduction	O
+of	O
+nucleosomal	O
+histone	B-GENE
+acetylation	O
+and	O
+alteration	O
+of	O
+chromatin	O
+structure	O
+.	O
+
+Recombinant	B-GENE
+BRI1	I-GENE
+-	I-GENE
+KD	I-GENE
+autophosphorylated	O
+on	O
+serine	O
+(	O
+Ser	O
+)	O
+and	O
+threonine	O
+(	O
+Thr	O
+)	O
+residues	O
+with	O
+p	O
+-	O
+Ser	O
+predominating	O
+.	O
+
+Flow	O
+cytomery	O
+was	O
+used	O
+for	O
+cell	O
+cycle	O
+analysis	O
+.	O
+
+Further	O
+research	O
+is	O
+required	O
+to	O
+better	O
+measure	O
+treatment	O
+effects	O
+,	O
+modification	O
+of	O
+MS	O
+natural	O
+history	O
+,	O
+and	O
+net	O
+societal	O
+costs	O
+of	O
+IFN	B-GENE
+beta	I-GENE
+-	I-GENE
+1b	I-GENE
+in	O
+RRMS	O
+.	O
+
+Cost	O
+-	O
+effectiveness	O
+of	O
+interferon	B-GENE
+beta	I-GENE
+-	I-GENE
+1b	I-GENE
+in	O
+slowing	O
+multiple	O
+sclerosis	O
+disability	O
+progression	O
+.	O
+
+Both	O
+the	O
+Cmax	O
+and	O
+AUC	O
+values	O
+were	O
+almost	O
+doubled	O
+with	O
+doubling	O
+the	O
+dose	O
+.	O
+
+Hyperactivation	O
+of	O
+Cdc2	B-GENE
+in	O
+fission	O
+yeast	O
+causes	O
+cells	O
+to	O
+undergo	O
+a	O
+lethal	O
+premature	O
+mitosis	O
+called	O
+mitotic	O
+catastrophe	O
+.	O
+
+Diary	O
+.	O
+
+Cells	O
+differentiate	O
+in	O
+response	O
+to	O
+various	O
+extracellular	O
+stimuli	O
+.	O
+
+Transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta1	I-GENE
+(	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+)	O
+can	O
+act	O
+as	O
+a	O
+tumor	O
+suppressor	O
+or	O
+a	O
+tumor	O
+promoter	O
+depending	O
+on	O
+the	O
+characteristics	O
+of	O
+the	O
+malignant	O
+cell	O
+.	O
+
+Mn2	O
++	O
+increased	O
+both	O
+the	O
+junction	O
+binding	O
+and	O
+cleaving	O
+activities	O
+of	O
+the	O
+mutant	O
+proteins	O
+.	O
+
+While	O
+Pt	B-GENE
+;	I-GENE
+cycH	I-GENE
+;	I-GENE
+1	I-GENE
+and	O
+Os	B-GENE
+;	I-GENE
+cycH	I-GENE
+;	I-GENE
+1	I-GENE
+were	O
+expressed	O
+in	O
+all	O
+tissues	O
+examined	O
+,	O
+the	O
+transcripts	O
+accumulated	O
+abundantly	O
+in	O
+dividing	O
+cells	O
+.	O
+
+Moreover	O
+,	O
+an	O
+in	O
+vitro	O
+pull	O
+-	O
+down	O
+assay	O
+showed	O
+that	O
+Os	B-GENE
+;	I-GENE
+CycH	I-GENE
+;	I-GENE
+1	I-GENE
+specifically	O
+bound	O
+to	O
+R2	B-GENE
+but	O
+not	O
+to	O
+other	O
+rice	B-GENE
+CDKs	I-GENE
+.	O
+
+In	O
+transient	O
+analysis	O
+using	O
+particle	O
+bombardment	O
+of	O
+tobacco	O
+leaf	O
+sections	O
+,	O
+a	O
+tetramer	O
+of	O
+the	O
+distB	O
+ABRE	O
+(	O
+abscisic	O
+acid	O
+-	O
+responsive	O
+element	O
+)	O
+mediated	O
+transactivation	O
+by	O
+ABI3	B-GENE
+and	O
+ABI3	B-GENE
+-	O
+dependent	O
+response	O
+to	O
+ABA	O
+,	O
+whereas	O
+a	O
+tetramer	O
+of	O
+the	O
+composite	O
+RY	O
+/	O
+G	O
+complex	O
+,	O
+containing	O
+RY	O
+repeats	O
+and	O
+a	O
+G	O
+-	O
+box	O
+,	O
+mediated	O
+only	O
+ABA	O
+-	O
+independent	O
+transactivation	O
+by	O
+ABI3	B-GENE
+.	O
+
+The	O
+major	O
+neurological	O
+manifestations	O
+of	O
+brain	O
+injury	O
+in	O
+these	O
+babies	O
+are	O
+spastic	O
+motor	O
+deficits	O
+.	O
+
+Spores	O
+from	O
+Rhizopus	O
+stolonifer	O
+were	O
+suspended	O
+in	O
+distilled	O
+water	O
+(	O
+1	O
+x	O
+10	O
+(	O
+6	O
+)	O
+spores	O
+/	O
+mL	O
+)	O
+and	O
+used	O
+as	O
+starter	O
+.	O
+
+The	O
+LMW	B-GENE
+FGF	I-GENE
+-	I-GENE
+2	I-GENE
+up	O
+-	O
+regulated	O
+the	O
+PKC	B-GENE
+epsilon	I-GENE
+levels	O
+by	O
+1	O
+.	O
+6	O
+-	O
+fold	O
+;	O
+by	O
+contrast	O
+the	O
+HMW	B-GENE
+isoform	I-GENE
+down	O
+-	O
+regulated	O
+the	O
+level	O
+of	O
+this	O
+PKC	B-GENE
+isotype	I-GENE
+by	O
+about	O
+3	O
+-	O
+fold	O
+and	O
+increased	O
+the	O
+amount	O
+of	O
+PKC	B-GENE
+delta	I-GENE
+by	O
+1	O
+.	O
+7	O
+-	O
+fold	O
+.	O
+
+Helicobacter	O
+pylori	O
+and	O
+stomach	O
+diseases	O
+:	O
+from	O
+clinical	O
+point	O
+of	O
+view	O
+
+For	O
+this	O
+purpose	O
+,	O
+the	O
+writhing	O
+test	O
+,	O
+capsaicin	O
+and	O
+formalin	O
+induced	O
+-	O
+pain	O
+in	O
+mice	O
+were	O
+used	O
+.	O
+
+2000	O
+update	O
+of	O
+recommendations	O
+for	O
+the	O
+use	O
+of	O
+hematopoietic	B-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factors	I-GENE
+:	O
+evidence	O
+-	O
+based	O
+,	O
+clinical	O
+practice	O
+guidelines	O
+.	O
+
+Prominent	O
+findings	O
+were	O
+chronic	O
+pancreatitis	O
+with	O
+acinar	O
+and	O
+ductal	O
+plugs	O
+,	O
+granulomatous	O
+and	O
+necrotizing	O
+peripancreatic	O
+steatitis	O
+,	O
+degenerative	O
+myopathy	O
+,	O
+testicular	O
+atrophy	O
+,	O
+candidiasis	O
+and	O
+bacterial	O
+necrotizing	O
+glossitis	O
+.	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+indicate	O
+that	O
+multiple	O
+survival	O
+pathways	O
+are	O
+triggered	O
+via	O
+this	O
+receptor	O
+,	O
+whereas	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+/	O
+Rel	B-GENE
+and	O
+PI	B-GENE
+-	I-GENE
+3K	I-GENE
+are	O
+crucial	O
+for	O
+CD40	B-GENE
+-	O
+induced	O
+proliferation	O
+.	O
+
+In	O
+vitro	O
+,	O
+Arix	B-GENE
+and	O
+NBPhox	B-GENE
+form	O
+DNA	O
+-	O
+independent	O
+multimers	O
+and	O
+exhibit	O
+cooperative	O
+binding	O
+to	O
+the	O
+DB1	B-GENE
+regulatory	I-GENE
+element	I-GENE
+,	O
+which	O
+contains	O
+two	O
+homeodomain	B-GENE
+recognition	I-GENE
+sites	I-GENE
+.	O
+
+We	O
+conclude	O
+from	O
+this	O
+study	O
+that	O
+Arix	B-GENE
+and	O
+NBPhox	B-GENE
+exhibit	O
+indistinguishable	O
+and	O
+independent	O
+transcriptional	O
+regulatory	O
+properties	O
+on	O
+the	O
+DBH	B-GENE
+promoter	I-GENE
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+Studies	O
+were	O
+undertaken	O
+in	O
+9	O
+isolated	O
+guinea	O
+pig	O
+hearts	O
+,	O
+which	O
+demonstrated	O
+reverse	O
+use	O
+-	O
+dependent	O
+prolongation	O
+of	O
+cardiac	O
+repolarization	O
+by	O
+100	O
+nmol	O
+/	O
+L	O
+domperidone	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+evaluate	O
+the	O
+overall	O
+performance	O
+of	O
+a	O
+new	O
+oscillometric	O
+wrist	O
+blood	O
+pressure	O
+monitor	O
+(	O
+Braun	O
+PrecisionSensor	O
+,	O
+Braun	O
+GmbH	O
+,	O
+Kronberg	O
+,	O
+Germany	O
+)	O
+as	O
+defined	O
+by	O
+the	O
+ANSI	O
+/	O
+AAMI	O
+SP10	O
+-	O
+1992	O
+guidelines	O
+,	O
+and	O
+to	O
+analyze	O
+the	O
+data	O
+for	O
+the	O
+optimized	O
+selection	O
+of	O
+the	O
+algorithm	O
+that	O
+derives	O
+the	O
+blood	O
+pressure	O
+values	O
+from	O
+the	O
+oscillometric	O
+blood	O
+pressure	O
+curves	O
+.	O
+
+Following	O
+the	O
+results	O
+of	O
+toxicological	O
+experiments	O
+in	O
+the	O
+target	O
+animals	O
+"	O
+Toxicological	O
+Drinking	O
+Water	O
+Standards	O
+for	O
+Animals	O
+"	O
+can	O
+be	O
+established	O
+.	O
+
+An	O
+increase	O
+in	O
+hypothalamic	O
+expression	O
+of	O
+at	O
+least	O
+two	O
+of	O
+the	O
+erbB	B-GENE
+receptors	I-GENE
+is	O
+initiated	O
+before	O
+the	O
+pubertal	O
+augmentation	O
+of	O
+gonadal	O
+steroid	O
+secretion	O
+and	O
+is	O
+completed	O
+on	O
+the	O
+day	O
+of	O
+the	O
+first	O
+preovulatory	O
+surge	O
+of	O
+gonadotropins	B-GENE
+.	O
+
+Dsh	B-GENE
+is	O
+required	O
+for	O
+two	O
+different	O
+pathways	O
+,	O
+the	O
+Wnt	B-GENE
+pathway	O
+and	O
+planar	O
+polarity	O
+pathway	O
+in	O
+Drosophila	O
+.	O
+
+Catch	O
+-	O
+up	O
+growth	O
+and	O
+craniofacial	O
+dimensions	O
+following	O
+administration	O
+of	O
+the	O
+antineoplastic	O
+agent	O
+vincristine	O
+to	O
+young	O
+rats	O
+.	O
+
+CONCLUSIONS	O
+:	O
+LSCC	O
+malformation	O
+,	O
+like	O
+other	O
+inner	O
+ear	O
+malformations	O
+such	O
+as	O
+large	O
+vestibular	O
+aqueduct	O
+and	O
+X	O
+-	O
+linked	O
+mixed	O
+deafness	O
+with	O
+perilymph	O
+gusher	O
+,	O
+can	O
+be	O
+associated	O
+with	O
+CHL	O
+,	O
+SNHL	O
+,	O
+or	O
+normal	O
+hearing	O
+.	O
+
+Escalation	O
+to	O
+180	O
+mg	O
+/	O
+m2	O
+was	O
+to	O
+be	O
+carried	O
+out	O
+if	O
+white	O
+blood	O
+cell	O
+nadir	O
+count	O
+was	O
+>	O
+2	O
+.	O
+0	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+l	O
+and	O
+platelet	O
+nadir	O
+count	O
+was	O
+>	O
+75	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+l	O
+.	O
+
+Methyl	O
+formate	O
+was	O
+used	O
+as	O
+the	O
+solvent	O
+of	O
+biodegradable	O
+oligoesters	O
+for	O
+the	O
+fabrication	O
+of	O
+microspheres	O
+with	O
+encapsulated	O
+bovine	B-GENE
+serum	I-GENE
+albumin	I-GENE
+(	O
+BSA	B-GENE
+)	O
+.	O
+
+The	O
+small	B-GENE
+monomeric	I-GENE
+GTP	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+of	O
+the	O
+RAB	B-GENE
+subfamily	I-GENE
+are	O
+key	O
+regulatory	O
+elements	O
+of	O
+the	O
+machinery	O
+that	O
+controls	O
+membrane	O
+traffic	O
+in	O
+eukaryotic	O
+cells	O
+.	O
+
+Furthermore	O
+,	O
+loss	O
+of	O
+methylation	O
+also	O
+greatly	O
+reduced	O
+the	O
+association	O
+of	O
+another	O
+yeast	O
+B	O
+-	O
+type	O
+subunit	O
+,	O
+Rts1p	B-GENE
+.	O
+
+Thus	O
+,	O
+methylation	O
+of	O
+Pph21p	B-GENE
+is	O
+important	O
+for	O
+formation	O
+of	O
+PP2A	B-GENE
+trimeric	I-GENE
+and	I-GENE
+dimeric	I-GENE
+complexes	I-GENE
+,	O
+and	O
+consequently	O
+,	O
+for	O
+PP2A	B-GENE
+function	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+analyze	O
+the	O
+temporal	O
+characteristics	O
+and	O
+the	O
+spatial	O
+mapping	O
+of	O
+the	O
+independent	O
+components	O
+identified	O
+by	O
+ICA	O
+when	O
+the	O
+subject	O
+performs	O
+a	O
+finger	O
+-	O
+tapping	O
+task	O
+.	O
+
+The	O
+authors	O
+present	O
+the	O
+only	O
+two	O
+studies	O
+that	O
+have	O
+proved	O
+successful	O
+in	O
+treating	O
+animal	O
+models	O
+of	O
+osteoarthritis	O
+using	O
+gene	O
+therapy	O
+,	O
+and	O
+propose	O
+an	O
+overview	O
+of	O
+several	O
+strategies	O
+for	O
+the	O
+development	O
+of	O
+gene	O
+therapy	O
+in	O
+osteoarthritis	O
+treatment	O
+in	O
+the	O
+future	O
+.	O
+
+Together	O
+,	O
+these	O
+results	O
+indicate	O
+that	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+induces	O
+VEGF	B-GENE
+gene	I-GENE
+expression	O
+at	O
+both	O
+transcriptional	O
+and	O
+post	O
+-	O
+transcriptional	O
+levels	O
+,	O
+and	O
+IL	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+evokes	O
+p38	B-GENE
+MAPK	O
+and	O
+JNK	B-GENE
+signalings	O
+,	O
+which	O
+in	O
+turn	O
+stimulate	O
+the	O
+transcription	O
+of	O
+the	O
+VEGF	B-GENE
+gene	I-GENE
+through	O
+Sp1	B-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+Binding	O
+of	O
+NusA	B-GENE
+to	O
+RNA	O
+in	O
+the	O
+presence	O
+of	O
+alpha	O
+or	O
+N	O
+involves	O
+an	O
+amino	B-GENE
+-	I-GENE
+terminal	I-GENE
+S1	I-GENE
+homology	I-GENE
+region	I-GENE
+that	O
+is	O
+otherwise	O
+inactive	O
+in	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+NusA	I-GENE
+.	O
+
+The	O
+subjects	O
+were	O
+diagnosed	O
+on	O
+the	O
+basis	O
+of	O
+DSM	O
+-	O
+IV	O
+pathological	O
+gambling	O
+criteria	O
+and	O
+completed	O
+the	O
+Turkish	O
+Version	O
+of	O
+South	O
+Oaks	O
+Gambling	O
+Screen	O
+(	O
+SOGS	O
+)	O
+.	O
+
+Lys	O
+(	O
+193	O
+)	O
+and	O
+Arg	O
+(	O
+194	O
+)	O
+,	O
+located	O
+at	O
+the	O
+COOH	O
+-	O
+terminal	O
+end	O
+of	O
+HD	B-GENE
+,	O
+are	O
+essential	O
+for	O
+dimerization	O
+.	O
+
+Elevation	O
+of	O
+intracellular	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+levels	O
+are	O
+also	O
+involved	O
+because	O
+treatment	O
+with	O
+receptor	O
+-	O
+associated	O
+protein	O
+,	O
+nifedipine	O
+,	O
+MK801	O
+,	O
+removal	O
+of	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+from	O
+the	O
+medium	O
+and	O
+dantrolene	O
+all	O
+served	O
+to	O
+inhibit	O
+calcium	O
+elevation	O
+and	O
+attenuate	O
+the	O
+activation	O
+of	O
+CREB	B-GENE
+.	O
+
+The	O
+present	O
+study	O
+shows	O
+that	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+-	O
+dependent	O
+p38	B-GENE
+kinase	I-GENE
+activation	O
+regulates	O
+Akt	B-GENE
+phosphorylation	O
+and	O
+activity	O
+in	O
+human	O
+neutrophils	O
+.	O
+
+When	O
+BFDS	O
+was	O
+taken	O
+as	O
+the	O
+reference	O
+,	O
+W	O
+/	O
+A	O
+Z	O
+scores	O
+showed	O
+consistent	O
+positive	O
+increments	O
+,	O
+from	O
+birth	O
+in	O
+girls	O
+and	O
+1	O
+mo	O
+in	O
+boys	O
+.	O
+
+Using	O
+purified	O
+recombinant	B-GENE
+HMG	I-GENE
+I	I-GENE
+,	O
+we	O
+have	O
+identified	O
+several	O
+high	O
+-	O
+affinity	O
+binding	O
+sites	O
+which	O
+overlap	O
+important	O
+transcription	O
+factor	O
+binding	O
+sites	O
+.	O
+
+High	B-GENE
+-	I-GENE
+mobility	I-GENE
+-	I-GENE
+group	I-GENE
+protein	I-GENE
+I	I-GENE
+can	O
+modulate	O
+binding	O
+of	O
+transcription	O
+factors	O
+to	O
+the	O
+U5	B-GENE
+region	I-GENE
+of	O
+the	O
+human	B-GENE
+immunodeficiency	I-GENE
+virus	I-GENE
+type	I-GENE
+1	I-GENE
+proviral	I-GENE
+promoter	I-GENE
+.	O
+
+Leptinaemia	O
+does	O
+not	O
+correlate	O
+with	O
+the	O
+actual	O
+or	O
+mean	O
+blood	O
+pressure	O
+reading	O
+nor	O
+with	O
+stage	O
+of	O
+hypertension	O
+according	O
+to	O
+the	O
+WHO	O
+classification	O
+.	O
+
+Thus	O
+,	O
+diamide	O
+treatment	O
+of	O
+nuclear	O
+extracts	O
+strongly	O
+reduces	O
+the	O
+binding	O
+of	O
+NFI	B-GENE
+proteins	I-GENE
+,	O
+and	O
+the	O
+addition	O
+of	O
+higher	O
+concentrations	O
+of	O
+dithiothreitol	O
+to	O
+nuclear	O
+extracts	O
+from	O
+TG	B-GENE
+-	O
+treated	O
+cells	O
+restores	O
+NFI	B-GENE
+-	I-GENE
+DNA	I-GENE
+binding	O
+to	O
+levels	O
+in	O
+extracts	O
+from	O
+untreated	O
+cells	O
+.	O
+
+LMP2A	B-GENE
+enhances	O
+Lyn	B-GENE
+and	O
+Syk	B-GENE
+ubiquitination	O
+in	O
+vivo	O
+in	O
+a	O
+fashion	O
+that	O
+depends	O
+on	O
+the	O
+activity	O
+of	O
+Nedd4	B-GENE
+family	O
+members	O
+and	O
+correlates	O
+with	O
+destabilization	O
+of	O
+the	O
+Lyn	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+.	O
+
+Further	O
+,	O
+Tax	B-GENE
+-	O
+mediated	O
+apoptosis	O
+was	O
+effectively	O
+prevented	O
+by	O
+ectopic	O
+expression	O
+of	O
+the	O
+p300	B-GENE
+coactivator	I-GENE
+.	O
+
+Our	O
+results	O
+,	O
+however	O
+,	O
+were	O
+obtained	O
+for	O
+Z	O
+itself	O
+and	O
+not	O
+for	O
+[	O
+Z	O
+]	O
+.	O
+
+Fisher	O
+'	O
+s	O
+exact	O
+test	O
+or	O
+Pearson	O
+'	O
+s	O
+chi2	O
+test	O
+were	O
+used	O
+for	O
+statistical	O
+analysis	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+the	O
+pregnant	O
+group	O
+,	O
+serum	O
+PP14	B-GENE
+concentrations	O
+were	O
+markedly	O
+increased	O
+after	O
+ET	O
+,	O
+and	O
+a	O
+significant	O
+difference	O
+between	O
+the	O
+pregnant	O
+group	O
+and	O
+the	O
+nonpregnant	O
+group	O
+was	O
+observed	O
+8	O
+days	O
+following	O
+ET	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+High	O
+expression	O
+of	O
+the	O
+peroxisome	B-GENE
+proliferator	I-GENE
+-	I-GENE
+activated	I-GENE
+receptor	I-GENE
+alpha	I-GENE
+(	O
+PPARalpha	B-GENE
+)	O
+differentiates	O
+brown	O
+fat	O
+from	O
+white	O
+,	O
+and	O
+is	O
+related	O
+to	O
+its	O
+high	O
+capacity	O
+of	O
+lipid	O
+oxidation	O
+.	O
+
+This	O
+-	O
+2485	O
+/	O
+-	O
+2458	O
+element	O
+bound	O
+PPARalpha	B-GENE
+and	O
+PPARgamma	B-GENE
+from	O
+brown	O
+fat	O
+nuclei	O
+.	O
+
+These	O
+results	O
+provide	O
+direct	O
+evidence	O
+for	O
+differential	O
+susceptibility	O
+to	O
+endonuclease	O
+-	O
+mediated	O
+mRNA	O
+decay	O
+resulting	O
+from	O
+the	O
+differential	O
+affinity	O
+of	O
+a	O
+RNA	O
+-	O
+binding	O
+protein	O
+for	O
+cis	O
+-	O
+acting	O
+stability	O
+determinants	O
+.	O
+
+RESULTS	O
+:	O
+Twenty	O
+-	O
+two	O
+(	O
+26	O
+%	O
+)	O
+patients	O
+had	O
+PHG	O
+before	O
+(	O
+group	O
+A	O
+)	O
+and	O
+64	O
+(	O
+74	O
+%	O
+)	O
+developed	O
+PHG	O
+after	O
+variceal	O
+eradication	O
+(	O
+group	O
+B	O
+)	O
+.	O
+
+Response	O
+was	O
+extremely	O
+poor	O
+in	O
+African	O
+Americans	O
+and	O
+those	O
+with	O
+HCV	O
+genotype	O
+1	O
+.	O
+
+Aspirin	O
+causes	O
+peptic	O
+ulcers	O
+predominately	O
+by	O
+reducing	O
+gastric	B-GENE
+mucosal	I-GENE
+cyclooxygenase	I-GENE
+(	O
+COX	B-GENE
+)	O
+activity	O
+and	O
+prostaglandin	O
+synthesis	O
+.	O
+
+A	O
+total	O
+of	O
+1060	O
+clones	O
+were	O
+randomly	O
+selected	O
+for	O
+sequencing	O
+of	O
+one	O
+end	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+surgical	O
+or	O
+multimodality	O
+treatment	O
+of	O
+MSGT	O
+has	O
+provided	O
+a	O
+good	O
+locoregional	O
+control	O
+(	O
+78	O
+%	O
+)	O
+and	O
+68	O
+%	O
+10	O
+-	O
+year	O
+survival	O
+in	O
+a	O
+series	O
+of	O
+patients	O
+treated	O
+at	O
+the	O
+oncology	O
+department	O
+of	O
+a	O
+general	O
+hospital	O
+in	O
+Quito	O
+,	O
+Ecuador	O
+.	O
+
+The	O
+gene	O
+is	O
+separated	O
+into	O
+four	O
+exons	O
+by	O
+three	O
+short	O
+introns	O
+,	O
+and	O
+the	O
+open	O
+reading	O
+frame	O
+consists	O
+of	O
+6660	O
+base	O
+pairs	O
+(	O
+bp	O
+)	O
+capable	O
+of	O
+encoding	O
+a	O
+polypeptide	O
+of	O
+2220	O
+amino	O
+acid	O
+residues	O
+.	O
+
+Like	O
+the	O
+p190	B-GENE
+-	I-GENE
+B	I-GENE
+exon	O
+,	O
+the	O
+first	O
+exon	O
+of	O
+p190	B-GENE
+-	I-GENE
+A	I-GENE
+is	O
+extremely	O
+large	O
+(	O
+3	O
+.	O
+7	O
+kb	O
+in	O
+length	O
+)	O
+,	O
+encoding	O
+both	O
+the	O
+GTPase	B-GENE
+and	O
+middle	O
+domains	O
+(	O
+residues	O
+1	O
+-	O
+1228	O
+)	O
+,	O
+but	O
+not	O
+the	O
+remaining	O
+GAP	B-GENE
+domain	I-GENE
+,	O
+suggesting	O
+a	O
+high	O
+conservation	O
+of	O
+genomic	O
+structure	O
+between	O
+two	O
+p190	B-GENE
+genes	I-GENE
+.	O
+
+The	O
+entire	O
+human	B-GENE
+teneurin	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+TEN1	B-GENE
+)	O
+gene	O
+is	O
+contained	O
+in	O
+eight	O
+PAC	O
+clones	O
+representing	O
+part	O
+of	O
+the	O
+chromosomal	O
+locus	O
+Xq25	O
+.	O
+
+The	O
+plexiform	O
+neurofibroma	O
+and	O
+multiple	O
+localized	O
+neurofibromas	O
+are	O
+characteristic	O
+of	O
+NF1	B-GENE
+.	O
+
+In	O
+general	O
+lookback	O
+,	O
+all	O
+patients	O
+who	O
+received	O
+blood	O
+before	O
+being	O
+tested	O
+for	O
+hepatitis	O
+C	O
+are	O
+advised	O
+to	O
+undergo	O
+testing	O
+.	O
+
+The	O
+proposed	O
+algorithm	O
+consists	O
+of	O
+several	O
+steps	O
+.	O
+
+It	O
+contained	O
+seven	O
+extra	O
+amino	O
+acids	O
+of	O
+FVVLNLQ	O
+;	O
+this	O
+short	O
+stretch	O
+of	O
+extra	O
+sequence	O
+was	O
+found	O
+between	O
+Gln	O
+(	O
+421	O
+)	O
+and	O
+Phe	O
+(	O
+422	O
+)	O
+within	O
+the	O
+SET	B-GENE
+(	O
+Suvar3	B-GENE
+-	I-GENE
+9	I-GENE
+,	O
+Enhancer	B-GENE
+-	I-GENE
+of	I-GENE
+-	I-GENE
+zeste	I-GENE
+,	O
+Trithorax	B-GENE
+)	O
+interacting	O
+domain	O
+(	O
+SID	O
+)	O
+of	O
+rMTM	B-GENE
+.	O
+
+MED1	B-GENE
+has	O
+a	O
+weak	O
+glycosylase	B-GENE
+activity	O
+on	O
+the	O
+mutagenic	O
+adduct	O
+3	O
+,	O
+N	O
+(	O
+4	O
+)	O
+-	O
+ethenocytosine	O
+,	O
+a	O
+metabolite	O
+of	O
+vinyl	O
+chloride	O
+and	O
+ethyl	O
+carbamate	O
+.	O
+
+There	O
+were	O
+no	O
+instances	O
+of	O
+major	O
+flap	O
+necrosis	O
+although	O
+two	O
+flaps	O
+showed	O
+tip	O
+ischaemia	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+XAB1	B-GENE
+is	O
+a	O
+novel	O
+cytoplasmic	B-GENE
+GTPase	I-GENE
+involved	O
+in	O
+nuclear	O
+localization	O
+of	O
+XPA	B-GENE
+.	O
+
+One	O
+of	O
+these	O
+factors	O
+,	O
+IRF	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+was	O
+initially	O
+cloned	O
+as	O
+an	O
+antagonistic	O
+counterpart	O
+to	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+with	O
+oncogenic	O
+potential	O
+.	O
+
+Among	O
+the	O
+total	O
+CDSs	O
+,	O
+8	O
+.	O
+8	O
+%	O
+match	O
+sequences	O
+of	O
+proteins	O
+found	O
+only	O
+in	O
+Bacillus	O
+subtilis	O
+and	O
+66	O
+.	O
+7	O
+%	O
+are	O
+widely	O
+conserved	O
+in	O
+comparison	O
+with	O
+the	O
+proteins	O
+of	O
+various	O
+organisms	O
+,	O
+including	O
+B	O
+.	O
+subtilis	O
+.	O
+
+Tobramycin	O
+-	O
+loaded	O
+SLN	O
+administered	O
+i	O
+.	O
+v	O
+.	O
+showed	O
+a	O
+prolonged	O
+circulation	O
+time	O
+compared	O
+to	O
+the	O
+i	O
+.	O
+v	O
+.	O
+administered	O
+tobramycin	O
+solution	O
+.	O
+
+Bacteriol	O
+.	O
+
+Terminal	B-GENE
+deoxynucleotidyl	I-GENE
+transferase	I-GENE
+-	O
+mediated	O
+nick	O
+end	O
+labeling	O
+assays	O
+revealed	O
+that	O
+hormonal	O
+activation	O
+of	O
+the	O
+PAX3	B-GENE
+repressors	I-GENE
+induced	O
+extensive	O
+apoptosis	O
+that	O
+correlated	O
+with	O
+down	O
+-	O
+regulation	O
+of	O
+BCL	B-GENE
+-	I-GENE
+X	I-GENE
+(	I-GENE
+L	I-GENE
+)	I-GENE
+expression	O
+.	O
+
+VEGF	B-GENE
+promoter	I-GENE
+activity	O
+in	O
+transient	O
+transfections	O
+was	O
+decreased	O
+by	O
+either	O
+pharmacological	O
+or	O
+genetic	O
+inhibition	O
+of	O
+EGFR	B-GENE
+,	O
+Ras	B-GENE
+,	O
+or	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+'	I-GENE
+-	I-GENE
+kinase	I-GENE
+[	B-GENE
+PI	I-GENE
+(	I-GENE
+3	I-GENE
+)	I-GENE
+kinase	I-GENE
+]	I-GENE
+.	O
+
+Epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+receptor	I-GENE
+transcriptionally	O
+up	O
+-	O
+regulates	O
+vascular	B-GENE
+endothelial	I-GENE
+growth	I-GENE
+factor	I-GENE
+expression	O
+in	O
+human	O
+glioblastoma	O
+cells	O
+via	O
+a	O
+pathway	O
+involving	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+'	I-GENE
+-	I-GENE
+kinase	I-GENE
+and	O
+distinct	O
+from	O
+that	O
+induced	O
+by	O
+hypoxia	O
+.	O
+
+Thus	O
+,	O
+IHHNV	O
+is	O
+closely	O
+related	O
+to	O
+densoviruses	O
+of	O
+the	O
+genus	O
+Brevidensovirus	O
+in	O
+the	O
+family	O
+Parvoviridae	O
+,	O
+and	O
+we	O
+therefore	O
+propose	O
+to	O
+rename	O
+this	O
+virus	O
+Penaeus	O
+stylirostris	O
+densovirus	O
+(	O
+PstDNV	O
+)	O
+.	O
+
+Stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+1	I-GENE
+(	O
+SAPK1	B-GENE
+)	O
+,	O
+also	O
+called	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+(	O
+JNK	B-GENE
+)	O
+,	O
+becomes	O
+activated	O
+in	O
+vivo	O
+in	O
+response	O
+to	O
+pro	O
+-	O
+inflammatory	O
+cytokines	O
+or	O
+cellular	O
+stresses	O
+.	O
+
+Catalytic	O
+activation	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+(	I-GENE
+MAP	I-GENE
+)	I-GENE
+kinase	I-GENE
+phosphatase	I-GENE
+-	I-GENE
+1	I-GENE
+by	O
+binding	O
+to	O
+p38	B-GENE
+MAP	I-GENE
+kinase	I-GENE
+:	O
+critical	O
+role	O
+of	O
+the	O
+p38	B-GENE
+C	I-GENE
+-	I-GENE
+terminal	I-GENE
+domain	I-GENE
+in	O
+its	O
+negative	O
+regulation	O
+.	O
+
+Thus	O
+,	O
+the	O
+class	B-GENE
+C	I-GENE
+-	O
+Vps	B-GENE
+complex	O
+directs	O
+multiple	O
+reactions	O
+during	O
+the	O
+docking	O
+and	O
+fusion	O
+of	O
+vesicles	O
+with	O
+the	O
+vacuole	O
+,	O
+each	O
+of	O
+which	O
+contributes	O
+to	O
+the	O
+overall	O
+specificity	O
+and	O
+efficiency	O
+of	O
+this	O
+transport	O
+process	O
+.	O
+
+Combined	O
+intravenous	O
+and	O
+intra	O
+-	O
+arterial	O
+recombinant	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+in	O
+acute	O
+ischemic	O
+stroke	O
+.	O
+
+Signal	O
+transduction	O
+via	O
+modulation	O
+of	O
+phosphorylation	O
+after	O
+selective	O
+inhibition	O
+of	O
+protein	B-GENE
+phosphatase	I-GENE
+(	I-GENE
+PP	I-GENE
+)	I-GENE
+1	I-GENE
+and	O
+/	O
+or	O
+PP2A	B-GENE
+appears	O
+to	O
+play	O
+a	O
+role	O
+in	O
+okadaic	O
+acid	O
+(	O
+OA	O
+)	O
+-	O
+mediated	O
+effects	O
+.	O
+
+Exon	O
+A	O
+is	O
+located	O
+approximately	O
+7	O
+kb	O
+5	O
+'	O
+to	O
+the	O
+HSL	B-GENE
+translation	I-GENE
+start	I-GENE
+site	I-GENE
+.	O
+
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+is	O
+a	O
+redox	O
+-	O
+sensitive	O
+transcription	O
+factor	O
+known	O
+to	O
+be	O
+activated	O
+by	O
+oxidative	O
+stress	O
+as	O
+well	O
+as	O
+chemical	O
+and	O
+biological	O
+reductants	O
+.	O
+
+Cardiovascular	O
+risk	O
+factors	O
+and	O
+antihypertensive	O
+treatment	O
+.	O
+
+What	O
+to	O
+look	O
+for	O
+during	O
+a	O
+compliance	O
+review	O
+:	O
+10	O
+common	O
+mistakes	O
+made	O
+by	O
+SNFs	O
+.	O
+
+CONCLUSIONS	O
+:	O
+EBCT	O
+technology	O
+allows	O
+minimally	O
+invasive	O
+evaluation	O
+of	O
+intramyocardial	O
+microcirculatory	O
+function	O
+and	O
+permits	O
+assessment	O
+of	O
+microvascular	O
+BV	O
+distribution	O
+in	O
+different	O
+functional	O
+components	O
+.	O
+
+These	O
+two	O
+mAbs	O
+used	O
+the	O
+same	O
+V	O
+(	O
+H	O
+)	O
+and	O
+J	O
+(	O
+H	O
+)	O
+gene	O
+segments	O
+,	O
+but	O
+different	O
+D	O
+,	O
+Vkappa	O
+,	O
+and	O
+Jkappa	O
+genes	O
+.	O
+
+SSF	O
+experiments	O
+were	O
+carried	O
+out	O
+in	O
+bench	O
+-	O
+scale	O
+bioreactors	O
+(	O
+equipped	O
+with	O
+CO2	O
+and	O
+volatile	O
+organic	O
+traps	O
+)	O
+containing	O
+a	O
+mixture	O
+of	O
+lignocellulosic	O
+materials	O
+and	O
+a	O
+radiolabeled	O
+pesticide	O
+.	O
+
+Characterization	O
+of	O
+a	O
+Xenopus	B-GENE
+laevis	I-GENE
+CXC	I-GENE
+chemokine	I-GENE
+receptor	I-GENE
+4	I-GENE
+:	O
+implications	O
+for	O
+hematopoietic	O
+cell	O
+development	O
+in	O
+the	O
+vertebrate	O
+embryo	O
+.	O
+
+Patients	O
+had	O
+to	O
+have	O
+adequate	O
+liver	O
+,	O
+renal	O
+,	O
+and	O
+marrow	O
+functions	O
+.	O
+
+Inhibition	O
+of	O
+RNA2	B-GENE
+translation	O
+was	O
+selective	O
+,	O
+with	O
+no	O
+effect	O
+on	O
+general	O
+cellular	O
+translation	O
+or	O
+translation	O
+of	O
+BMV	O
+RNA1	B-GENE
+-	O
+encoded	O
+replication	B-GENE
+factor	I-GENE
+1a	I-GENE
+,	O
+and	O
+was	O
+independent	O
+of	O
+p20	B-GENE
+,	O
+a	O
+cellular	O
+antagonist	O
+of	O
+DED1	B-GENE
+function	O
+in	O
+translation	O
+.	O
+
+Abbreviations	O
+:	O
+CAS	B-GENE
+,	O
+CRK	B-GENE
+-	I-GENE
+associated	I-GENE
+substrate	I-GENE
+;	O
+CH	B-GENE
+,	O
+calponin	B-GENE
+-	I-GENE
+homology	I-GENE
+domain	I-GENE
+;	O
+CSK	B-GENE
+,	O
+C	B-GENE
+-	I-GENE
+terminal	I-GENE
+SRC	I-GENE
+kinase	I-GENE
+;	O
+E6	B-GENE
+,	O
+Papillomavirus	B-GENE
+E6	I-GENE
+protein	I-GENE
+;	O
+FAK	B-GENE
+,	O
+focal	B-GENE
+adhesion	I-GENE
+kinase	I-GENE
+;	O
+GIT	B-GENE
+,	O
+GRK	B-GENE
+interacter	I-GENE
+;	O
+GPCR	B-GENE
+,	O
+heterotrimeric	B-GENE
+-	I-GENE
+G	I-GENE
+-	I-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+receptor	I-GENE
+;	O
+GRK	B-GENE
+,	O
+G	B-GENE
+-	I-GENE
+protein	I-GENE
+-	I-GENE
+coupled	I-GENE
+-	I-GENE
+receptor	I-GENE
+kinase	I-GENE
+;	O
+MAPK	B-GENE
+,	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+ERK	B-GENE
+,	O
+p38	B-GENE
+,	O
+JNK	B-GENE
+)	O
+;	O
+PAK	B-GENE
+,	O
+p21	B-GENE
+-	I-GENE
+activated	I-GENE
+kinase	I-GENE
+;	O
+PBS	B-GENE
+,	O
+paxillin	B-GENE
+-	I-GENE
+binding	I-GENE
+subdomain	I-GENE
+;	O
+PIX	B-GENE
+,	O
+PAK	B-GENE
+-	I-GENE
+interacting	I-GENE
+exchange	I-GENE
+factor	I-GENE
+;	O
+PKL	B-GENE
+,	O
+paxillin	B-GENE
+kinase	I-GENE
+linker	I-GENE
+;	O
+POR1	B-GENE
+,	O
+partner	B-GENE
+of	I-GENE
+Rac	I-GENE
+;	O
+PS	O
+,	O
+phosphoserine	O
+;	O
+PT	O
+,	O
+phosphothreonine	O
+;	O
+PY	O
+,	O
+phosphotyrosine	O
+;	O
+RTK	B-GENE
+,	O
+growth	B-GENE
+factor	I-GENE
+receptor	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+;	O
+SH	B-GENE
+,	O
+SRC	B-GENE
+-	I-GENE
+homology	I-GENE
+domain	I-GENE
+.	O
+
+In	O
+15	O
+ventilator	O
+-	O
+dependent	O
+,	O
+SB	O
+,	O
+and	O
+actively	O
+expiring	O
+patients	O
+,	O
+we	O
+found	O
+that	O
+the	O
+difference	O
+PEEP	O
+(	O
+i	O
+)	O
+,	O
+dyn	O
+-	O
+Pga	O
+,	O
+total	O
+decay	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+,	O
+5	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+cm	O
+H	O
+(	O
+2	O
+)	O
+O	O
+)	O
+was	O
+quite	O
+similar	O
+to	O
+PEEP	O
+(	O
+i	O
+)	O
+,	O
+dyn	O
+ref	O
+(	O
+5	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+cm	O
+H	O
+(	O
+2	O
+)	O
+O	O
+)	O
+.	O
+
+Of	O
+208	O
+eligible	O
+subjects	O
+,	O
+82	O
+received	O
+supervised	O
+IPT	O
+at	O
+a	O
+dose	O
+of	O
+900	O
+mg	O
+twice	O
+weekly	O
+for	O
+6	O
+mo	O
+(	O
+Regimen	O
+A	O
+)	O
+,	O
+73	O
+received	O
+unsupervised	O
+IPT	O
+900	O
+mg	O
+twice	O
+weekly	O
+for	O
+6	O
+mo	O
+(	O
+Regimen	O
+B	O
+)	O
+,	O
+and	O
+53	O
+received	O
+unsupervised	O
+IPT	O
+300	O
+mg	O
+daily	O
+for	O
+6	O
+mo	O
+(	O
+Regimen	O
+C	O
+)	O
+.	O
+
+There	O
+were	O
+122	O
+cases	O
+of	O
+tuberculosis	O
+over	O
+an	O
+average	O
+10	O
+.	O
+3	O
+yr	O
+of	O
+follow	O
+-	O
+up	O
+(	O
+crude	O
+annual	O
+incidence	O
+,	O
+76	O
+.	O
+2	O
+/	O
+100	O
+,	O
+000	O
+)	O
+.	O
+
+These	O
+results	O
+suggested	O
+that	O
+BACH1t	B-GENE
+recruits	O
+BACH1	B-GENE
+to	O
+the	O
+nucleus	O
+through	O
+BTB	B-GENE
+domain	O
+-	O
+mediated	O
+interaction	O
+.	O
+
+Transcription	O
+of	O
+the	O
+six	O
+EBNA	B-GENE
+genes	I-GENE
+,	O
+which	O
+are	O
+expressed	O
+in	O
+EBV	O
+-	O
+immortalized	O
+primary	O
+B	O
+cells	O
+,	O
+arises	O
+from	O
+one	O
+of	O
+two	O
+promoters	O
+,	O
+Cp	B-GENE
+and	O
+Wp	B-GENE
+,	O
+located	O
+near	O
+the	O
+left	O
+end	O
+of	O
+the	O
+viral	O
+genome	O
+.	O
+
+Thus	O
+,	O
+blocks	O
+in	O
+the	O
+RARalpha	B-GENE
+-	O
+specific	O
+pathway	O
+of	O
+retinoid	O
+-	O
+induced	O
+differentiation	O
+may	O
+be	O
+bypassed	O
+during	O
+retinoid	O
+induction	O
+of	O
+FR	B-GENE
+-	I-GENE
+beta	I-GENE
+expression	O
+.	O
+
+Is	O
+more	O
+better	O
+?	O
+About	O
+dose	O
+levels	O
+of	O
+ACE	B-GENE
+inhibitors	O
+in	O
+chronic	O
+heart	O
+failure	O
+.	O
+
+To	O
+test	O
+whether	O
+or	O
+not	O
+SOCS	B-GENE
+-	I-GENE
+3	I-GENE
+also	O
+binds	O
+to	O
+the	O
+IGFIR	B-GENE
+,	O
+we	O
+cloned	O
+human	B-GENE
+SOCS	I-GENE
+-	I-GENE
+3	I-GENE
+by	O
+reverse	O
+transcription	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+from	O
+human	O
+skeletal	O
+muscle	O
+mRNA	O
+.	O
+
+A	O
+protein	O
+lacking	O
+the	O
+SH2	B-GENE
+and	O
+RING	O
+finger	O
+domains	O
+has	O
+no	O
+activity	O
+,	O
+but	O
+a	O
+chimeric	O
+protein	O
+with	O
+the	O
+SH2	B-GENE
+and	O
+RING	O
+finger	O
+domains	O
+of	O
+SLI	B-GENE
+-	I-GENE
+1	I-GENE
+replaced	O
+by	O
+the	O
+equivalent	O
+domains	O
+of	O
+c	B-GENE
+-	I-GENE
+Cbl	I-GENE
+has	O
+activity	O
+.	O
+
+To	O
+evaluate	O
+the	O
+effects	O
+of	O
+HRT	O
+on	O
+those	O
+factors	O
+in	O
+end	O
+-	O
+stage	O
+renal	O
+disease	O
+(	O
+ESRD	O
+)	O
+patients	O
+,	O
+we	O
+evaluated	O
+the	O
+changes	O
+of	O
+lipid	O
+profile	O
+,	O
+coagulation	O
+and	O
+fibrinolysis	O
+markers	O
+,	O
+and	O
+plasma	O
+homocysteine	O
+levels	O
+after	O
+treatment	O
+.	O
+
+There	O
+was	O
+a	O
+weak	O
+significant	O
+correlation	O
+between	O
+TGF	B-GENE
+beta	I-GENE
+1	I-GENE
+levels	O
+and	O
+normal	O
+cell	O
+radiosensitivity	O
+(	O
+lymphocyte	O
+SF2	O
+)	O
+.	O
+
+Acute	O
+feasibility	O
+and	O
+safety	O
+of	O
+a	O
+smoking	O
+reduction	O
+strategy	O
+for	O
+smokers	O
+with	O
+schizophrenia	O
+.	O
+
+Tightly	O
+ordered	O
+proteasomal	O
+degradation	O
+of	O
+proteins	O
+critical	O
+for	O
+cell	O
+cycle	O
+control	O
+implies	O
+a	O
+role	O
+of	O
+the	O
+proteasome	O
+in	O
+maintaining	O
+cell	O
+proliferation	O
+and	O
+cell	O
+survival	O
+.	O
+
+The	O
+sixth	O
+nucleotide	O
+was	O
+bulged	O
+out	O
+to	O
+allow	O
+stacking	O
+of	O
+this	O
+U	O
+.	O
+G	O
+pair	O
+on	O
+the	O
+adjacent	O
+helical	O
+region	O
+.	O
+
+Functional	O
+analysis	O
+of	O
+the	O
+mutant	B-GENE
+desmin	I-GENE
+in	O
+SW13	O
+(	O
+vim	B-GENE
+-	O
+)	O
+cells	O
+showed	O
+aggregation	O
+of	O
+abnormal	O
+coarse	O
+clumps	O
+of	O
+desmin	B-GENE
+positive	O
+material	O
+dispersed	O
+throughout	O
+the	O
+cytoplasm	O
+.	O
+
+Patients	O
+with	O
+lesions	O
+affecting	O
+the	O
+PRC	O
+but	O
+sparing	O
+the	O
+PHC	O
+,	O
+and	O
+patients	O
+with	O
+lesions	O
+affecting	O
+both	O
+PRC	O
+and	O
+PHC	O
+,	O
+performed	O
+an	O
+oculomotor	O
+delayed	O
+response	O
+task	O
+with	O
+unpredictably	O
+varied	O
+memory	O
+delays	O
+of	O
+up	O
+to	O
+30	O
+s	O
+.	O
+
+In	O
+addition	O
+,	O
+26	O
+amino	O
+acid	O
+residues	O
+,	O
+K69	O
+,	O
+D88	O
+,	O
+E94	O
+,	O
+D134	O
+,	O
+R154	O
+,	O
+K169	O
+,	O
+H197	O
+,	O
+D233	O
+,	O
+G235	O
+,	O
+G236	O
+,	O
+G237	O
+,	O
+F238	O
+,	O
+E274	O
+,	O
+G276	O
+,	O
+R277	O
+,	O
+Y278	O
+,	O
+K294	O
+,	O
+Y323	O
+,	O
+Y331	O
+,	O
+D332	O
+,	O
+C360	O
+,	O
+D361	O
+,	O
+D364	O
+,	O
+G387	O
+,	O
+Y389	O
+,	O
+and	O
+F397	O
+(	O
+mouse	O
+ODC	B-GENE
+numbering	O
+)	O
+,	O
+all	O
+of	O
+which	O
+are	O
+implicated	O
+in	O
+the	O
+formation	O
+of	O
+the	O
+pyridoxal	O
+phosphate	O
+-	O
+binding	O
+domain	O
+and	O
+the	O
+substrate	O
+-	O
+binding	O
+domain	O
+and	O
+in	O
+dimer	O
+stabilization	O
+with	O
+the	O
+eukaryotic	O
+ODCs	B-GENE
+,	O
+were	O
+also	O
+conserved	O
+in	O
+S	O
+.	O
+ruminantium	O
+LDC	B-GENE
+.	O
+
+The	O
+Psc2	B-GENE
+cDNA	I-GENE
+contained	O
+an	O
+open	O
+reading	O
+frame	O
+homologous	O
+to	O
+CP2	B-GENE
+family	I-GENE
+proteins	I-GENE
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+Shh	B-GENE
+can	O
+drive	O
+continued	O
+cycling	O
+in	O
+immature	O
+,	O
+proliferating	O
+CGNPs	O
+.	O
+
+The	O
+QT	O
+interval	O
+was	O
+related	O
+to	O
+various	O
+components	O
+of	O
+the	O
+insulin	B-GENE
+resistance	O
+syndrome	O
+,	O
+including	O
+BP	O
+and	O
+insulin	B-GENE
+sensitivity	O
+.	O
+
+The	O
+wavenumbers	O
+corresponding	O
+to	O
+the	O
+normal	O
+modes	O
+of	O
+vibration	O
+were	O
+calculated	O
+using	O
+the	O
+DFT	O
+(	O
+B3LYP	O
+/	O
+6	O
+-	O
+31G	O
+*	O
+*	O
+)	O
+approximation	O
+and	O
+their	O
+agreement	O
+with	O
+the	O
+measured	O
+values	O
+improved	O
+after	O
+scaling	O
+of	O
+the	O
+associated	O
+force	O
+field	O
+.	O
+
+The	O
+data	O
+provide	O
+strong	O
+evidence	O
+that	O
+ThlA	B-GENE
+is	O
+involved	O
+in	O
+the	O
+metabolism	O
+of	O
+both	O
+acid	O
+and	O
+solvent	O
+formation	O
+,	O
+whereas	O
+the	O
+physiological	O
+function	O
+of	O
+ThlB	B-GENE
+has	O
+yet	O
+to	O
+be	O
+elucidated	O
+.	O
+
+In	O
+addition	O
+,	O
+npm3	B-GENE
+,	O
+which	O
+is	O
+usually	O
+coactivated	O
+with	O
+fgf8	B-GENE
+by	O
+MMTV	O
+insertion	O
+,	O
+was	O
+not	O
+up	O
+-	O
+regulated	O
+by	O
+androgens	O
+in	O
+SC	O
+-	O
+3	O
+cells	O
+.	O
+
+Experiments	O
+with	O
+epitope	O
+-	O
+tagged	O
+proteins	O
+show	O
+that	O
+UEV1A	B-GENE
+is	O
+a	O
+nuclear	O
+protein	O
+,	O
+whereas	O
+both	O
+Kua	B-GENE
+and	O
+Kua	B-GENE
+-	O
+UEV	B-GENE
+localize	O
+to	O
+cytoplasmic	O
+structures	O
+,	O
+indicating	O
+that	O
+the	O
+Kua	B-GENE
+domain	I-GENE
+determines	O
+the	O
+cytoplasmic	O
+localization	O
+of	O
+Kua	B-GENE
+-	O
+UEV	B-GENE
+.	O
+
+Stoichiometric	O
+phosphorylation	O
+of	O
+human	B-GENE
+p53	I-GENE
+at	O
+Ser315	O
+stimulates	O
+p53	B-GENE
+-	O
+dependent	O
+transcription	O
+.	O
+p53	B-GENE
+protein	I-GENE
+activity	O
+as	O
+a	O
+transcription	O
+factor	O
+can	O
+be	O
+activated	O
+in	O
+vivo	O
+by	O
+antibodies	O
+that	O
+target	O
+its	O
+C	O
+-	O
+terminal	O
+negative	O
+regulatory	O
+domain	O
+suggesting	O
+that	O
+cellular	O
+enzymes	O
+that	O
+target	O
+this	O
+domain	O
+may	O
+play	O
+a	O
+role	O
+in	O
+stimulating	O
+p53	B-GENE
+-	O
+dependent	O
+gene	O
+expression	O
+.	O
+
+Interestingly	O
+,	O
+this	O
+mutant	O
+cell	O
+line	O
+lacks	O
+expression	O
+of	O
+the	O
+IKK	B-GENE
+regulatory	I-GENE
+protein	I-GENE
+,	O
+IKKgamma	B-GENE
+.	O
+
+The	O
+Tax	B-GENE
+/	O
+IKKgamma	B-GENE
+interaction	O
+serves	O
+to	O
+recruit	O
+Tax	B-GENE
+to	O
+the	O
+IKK	B-GENE
+catalytic	I-GENE
+subunits	I-GENE
+,	O
+IKKalpha	B-GENE
+and	O
+IKKbeta	B-GENE
+,	O
+and	O
+this	O
+recruitment	O
+appears	O
+to	O
+be	O
+an	O
+essential	O
+mechanism	O
+by	O
+which	O
+Tax	B-GENE
+stimulates	O
+the	O
+activity	O
+of	O
+IKK	B-GENE
+.	O
+
+An	O
+anchored	O
+AFLP	O
+-	O
+and	O
+retrotransposon	O
+-	O
+based	O
+map	O
+of	O
+diploid	O
+Avena	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+identified	O
+a	O
+novel	O
+type	O
+of	O
+inhibitory	O
+domain	O
+in	O
+the	O
+N	O
+-	O
+terminal	O
+60	O
+amino	O
+acids	O
+of	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+which	O
+strongly	O
+inhibits	O
+its	O
+transcriptional	O
+activity	O
+.	O
+
+Simultaneous	O
+determination	O
+of	O
+theophylline	O
+and	O
+its	O
+metabolites	O
+by	O
+HPLC	O
+]	O
+A	O
+high	O
+performance	O
+liquid	O
+chromatography	O
+(	O
+HPLC	O
+)	O
+method	O
+has	O
+been	O
+developed	O
+for	O
+the	O
+simultaneous	O
+determination	O
+of	O
+theophylline	O
+and	O
+its	O
+metabolites	O
+,	O
+with	O
+caffeine	O
+and	O
+its	O
+metabolites	O
+.	O
+
+Ten	O
+males	O
+performed	O
+both	O
+test	O
+conditions	O
+and	O
+oxygen	O
+uptake	O
+VO2	O
+,	O
+heart	O
+rate	O
+,	O
+minute	O
+ventilation	O
+VE	O
+,	O
+perceived	O
+exertion	O
+and	O
+spinal	O
+shrinkage	O
+were	O
+recorded	O
+.	O
+
+CONCLUSION	O
+:	O
+SPT	O
+is	O
+more	O
+useful	O
+than	O
+WST	O
+in	O
+differentiating	O
+patients	O
+predisposed	O
+to	O
+aspiration	O
+.	O
+
+Studied	O
+groups	O
+were	O
+(	O
+1	O
+)	O
+untreated	O
+control	O
+,	O
+n	O
+=	O
+12	O
+;	O
+(	O
+2	O
+)	O
+FK	O
+-	O
+1	O
+,	O
+n	O
+=	O
+8	O
+;	O
+(	O
+3	O
+)	O
+FK	O
+-	O
+3	O
+,	O
+n	O
+=	O
+8	O
+.	O
+
+DNA	O
+binding	O
+and	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+pull	O
+-	O
+down	O
+assays	O
+demonstrate	O
+that	O
+binding	O
+requires	O
+Elk	B-GENE
+-	I-GENE
+1	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+212	I-GENE
+)	I-GENE
+but	O
+not	O
+the	O
+C	O
+-	O
+terminal	O
+transactivation	O
+domain	O
+.	O
+
+Unexpectedly	O
+,	O
+ALK7	B-GENE
+signaling	O
+produced	O
+a	O
+remarkable	O
+change	O
+in	O
+cell	O
+morphology	O
+characterized	O
+by	O
+cell	O
+flattening	O
+and	O
+elaboration	O
+of	O
+blunt	O
+,	O
+short	O
+cell	O
+processes	O
+.	O
+
+The	O
+swa2	B-GENE
+-	I-GENE
+1	I-GENE
+allele	I-GENE
+recovered	O
+from	O
+the	O
+original	O
+screen	O
+carries	O
+a	O
+point	O
+mutation	O
+in	O
+its	O
+tetratricopeptide	O
+repeat	O
+(	O
+TPR	O
+)	O
+domain	O
+,	O
+a	O
+motif	O
+not	O
+found	O
+in	O
+auxilin	B-GENE
+but	O
+known	O
+in	O
+other	O
+proteins	O
+to	O
+mediate	O
+interaction	O
+with	O
+heat	B-GENE
+-	I-GENE
+shock	I-GENE
+proteins	I-GENE
+.	O
+
+In	O
+slightly	O
+older	O
+embryos	O
+,	O
+the	O
+expression	O
+was	O
+skewed	O
+to	O
+one	O
+side	O
+of	O
+the	O
+embryo	O
+and	O
+by	O
+E6	O
+.	O
+5	O
+,	O
+at	O
+the	O
+onset	O
+of	O
+gastrulation	O
+,	O
+expression	O
+was	O
+seen	O
+in	O
+the	O
+epiblast	O
+,	O
+visceral	O
+endoderm	O
+,	O
+nascent	O
+mesoderm	O
+,	O
+and	O
+the	O
+primitive	O
+streak	O
+.	O
+
+The	O
+authors	O
+proposed	O
+that	O
+the	O
+highly	O
+convergent	O
+inputs	O
+to	O
+the	O
+entorhinal	O
+cortex	O
+indicate	O
+this	O
+region	O
+may	O
+be	O
+particularly	O
+important	O
+for	O
+selecting	O
+or	O
+compressing	O
+information	O
+.	O
+
+Influence	O
+of	O
+oil	O
+emulsions	O
+and	O
+diphenyl	O
+on	O
+post	O
+-	O
+harvest	O
+physiconutritional	O
+changes	O
+in	O
+Kagzi	O
+limes	O
+(	O
+Citrus	O
+aurantifolia	O
+)	O
+was	O
+studied	O
+.	O
+
+Detailed	O
+analysis	O
+of	O
+alpha1	B-GENE
+,	I-GENE
+3GT	I-GENE
+transcripts	I-GENE
+revealed	O
+two	O
+major	O
+alternative	O
+splicing	O
+patterns	O
+in	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+(	O
+5	O
+'	O
+-	O
+UTR	O
+)	O
+and	O
+evidence	O
+for	O
+minor	O
+splicing	O
+activity	O
+that	O
+occurs	O
+in	O
+a	O
+tissue	O
+-	O
+specific	O
+manner	O
+.	O
+
+A	O
+thermal	O
+Kubo	O
+-	O
+Martin	O
+-	O
+Schwinger	O
+condition	O
+arises	O
+due	O
+to	O
+the	O
+coupling	O
+of	O
+a	O
+computer	O
+to	O
+a	O
+strong	O
+periodic	O
+source	O
+,	O
+namely	O
+,	O
+the	O
+daily	O
+and	O
+weekly	O
+usage	O
+patterns	O
+of	O
+the	O
+system	O
+.	O
+
+The	O
+non	O
+-	O
+homologous	O
+sequences	O
+in	O
+the	O
+5	O
+'	O
+untranslated	O
+regions	O
+might	O
+be	O
+acquired	O
+at	O
+or	O
+after	O
+transcription	O
+during	O
+retrotransposition	O
+of	O
+the	O
+ATLN	O
+elements	O
+.	O
+
+The	O
+time	O
+course	O
+of	O
+RNA1	B-GENE
+replication	O
+and	O
+RNA3	B-GENE
+synthesis	O
+in	O
+induced	O
+yeast	O
+paralleled	O
+that	O
+in	O
+yeast	O
+transfected	O
+with	O
+natural	O
+FHV	O
+virion	O
+RNA	O
+.	O
+
+The	O
+transcription	O
+and	O
+alternative	O
+splicing	O
+of	O
+human	B-GENE
+ORL1	I-GENE
+and	O
+GAIP	B-GENE
+are	O
+cell	O
+-	O
+type	O
+specific	O
+.	O
+
+The	O
+extraction	O
+was	O
+subsequently	O
+rated	O
+as	O
+'	O
+easy	O
+'	O
+or	O
+'	O
+difficult	O
+'	O
+.	O
+Taking	O
+Pell	O
+-	O
+Gregory	O
+class	O
+C	O
+as	O
+a	O
+predictor	O
+of	O
+a	O
+'	O
+difficult	O
+'	O
+extraction	O
+,	O
+specificity	O
+was	O
+88	O
+%	O
+but	O
+sensitivity	O
+was	O
+low	O
+at	O
+15	O
+%	O
+.	O
+
+In	O
+addition	O
+,	O
+our	O
+results	O
+show	O
+that	O
+ERKs	B-GENE
+and	O
+PI3Ks	B-GENE
+can	O
+synergise	O
+to	O
+convert	O
+ectoderm	O
+into	O
+mesoderm	O
+.	O
+
+Nevertheless	O
+,	O
+protein	B-GENE
+kinase	I-GENE
+A	I-GENE
+stimulation	O
+induces	O
+CREMalpha	B-GENE
+to	O
+activate	O
+the	O
+complex	O
+native	O
+promoter	O
+in	O
+the	O
+phosphoenolpyruvate	B-GENE
+carboxykinase	I-GENE
+(	O
+PEPCK	B-GENE
+)	O
+gene	O
+.	O
+
+Another	O
+putative	O
+HNF3	B-GENE
+site	I-GENE
+in	O
+close	O
+apposition	O
+to	O
+a	O
+NF1	B-GENE
+/	O
+CTF	B-GENE
+site	O
+was	O
+localized	O
+upstream	O
+of	O
+the	O
+silencer	O
+-	O
+like	O
+element	O
+.	O
+
+A	O
+recently	O
+reported	O
+new	O
+member	O
+of	O
+the	O
+Vav	B-GENE
+family	I-GENE
+proteins	I-GENE
+,	O
+Vav3	B-GENE
+has	O
+been	O
+identified	O
+as	O
+a	O
+Ros	B-GENE
+receptor	B-GENE
+protein	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+(	O
+RPTK	B-GENE
+)	O
+interacting	O
+protein	O
+by	O
+yeast	O
+two	O
+-	O
+hybrid	O
+screening	O
+.	O
+
+Subsequently	O
+,	O
+we	O
+show	O
+that	O
+the	O
+reexpression	O
+of	O
+the	O
+r	B-GENE
+-	I-GENE
+PTPeta	I-GENE
+gene	I-GENE
+in	O
+highly	O
+malignant	O
+rat	O
+thyroid	O
+cells	O
+transformed	O
+by	O
+retroviruses	O
+carrying	O
+the	O
+v	B-GENE
+-	I-GENE
+mos	I-GENE
+and	O
+v	B-GENE
+-	I-GENE
+ras	I-GENE
+-	I-GENE
+Ki	I-GENE
+oncogenes	I-GENE
+suppresses	O
+their	O
+malignant	O
+phenotype	O
+.	O
+
+Induced	O
+expression	O
+of	O
+Rnd3	B-GENE
+is	O
+associated	O
+with	O
+transformation	O
+of	O
+polarized	O
+epithelial	O
+cells	O
+by	O
+the	O
+Raf	B-GENE
+-	O
+MEK	B-GENE
+-	O
+extracellular	O
+signal	O
+-	O
+regulated	O
+kinase	O
+pathway	O
+.	O
+
+The	O
+activity	O
+of	O
+the	O
+transcription	B-GENE
+factor	I-GENE
+CREB	I-GENE
+is	O
+regulated	O
+by	O
+extracellular	O
+stimuli	O
+that	O
+result	O
+in	O
+its	O
+phosphorylation	O
+at	O
+a	O
+critical	O
+serine	O
+residue	O
+,	O
+Ser133	O
+.	O
+
+When	O
+10	O
+fields	O
+were	O
+analysed	O
+,	O
+a	O
+strong	O
+relationship	O
+was	O
+found	O
+between	O
+the	O
+presence	O
+of	O
+bacteria	O
+on	O
+Gram	O
+staining	O
+and	O
+the	O
+final	O
+diagnosis	O
+of	O
+VAP	O
+(	O
+for	O
+PSB	O
+and	O
+PTC	O
+respectively	O
+:	O
+sensitivity	O
+74	O
+and	O
+81	O
+%	O
+,	O
+specificity	O
+94	O
+and	O
+100	O
+%	O
+,	O
+positive	O
+predictive	O
+value	O
+91	O
+and	O
+100	O
+%	O
+,	O
+negative	O
+predictive	O
+value	O
+82	O
+and	O
+88	O
+%	O
+)	O
+.	O
+
+Tranilast	O
+in	O
+the	O
+Therapy	O
+of	O
+Coronary	O
+Artery	O
+Disease	O
+.	O
+
+This	O
+study	O
+is	O
+a	O
+further	O
+and	O
+more	O
+extensive	O
+validation	O
+of	O
+the	O
+clinician	O
+rated	O
+NIMH	O
+-	O
+LCM	O
+-	O
+p	O
+.	O
+
+The	O
+Aie1	B-GENE
+locus	I-GENE
+was	O
+mapped	O
+to	O
+mouse	O
+chromosome	O
+7A2	O
+-	O
+A3	O
+by	O
+fluorescent	O
+in	O
+situ	O
+hybridization	O
+.	O
+
+Psychiatric	O
+disorders	O
+in	O
+children	O
+and	O
+adolescents	O
+carry	O
+considerable	O
+morbidity	O
+,	O
+impede	O
+development	O
+,	O
+and	O
+carry	O
+a	O
+significant	O
+mortality	O
+by	O
+suicide	O
+.	O
+
+Thyrotoxicosis	O
+due	O
+to	O
+amiodarone	O
+is	O
+difficult	O
+to	O
+treat	O
+and	O
+is	O
+further	O
+complicated	O
+by	O
+the	O
+pro	O
+-	O
+arrhythmic	O
+potential	O
+of	O
+thyrotoxicosis	O
+and	O
+the	O
+fading	O
+antiarrhythmic	O
+effect	O
+after	O
+amiodarone	O
+withdrawal	O
+.	O
+
+Chaperones	O
+/	O
+HSPs	B-GENE
+thus	O
+play	O
+important	O
+roles	O
+within	O
+cell	O
+cycle	O
+processes	O
+.	O
+
+This	O
+study	O
+allows	O
+us	O
+to	O
+draw	O
+conclusions	O
+about	O
+the	O
+identity	O
+of	O
+proteins	O
+required	O
+for	O
+the	O
+development	O
+of	O
+the	O
+nervous	O
+system	O
+in	O
+Drosophila	O
+and	O
+provides	O
+an	O
+example	O
+of	O
+a	O
+molecular	O
+approach	O
+to	O
+characterize	O
+en	O
+masse	O
+transposon	O
+-	O
+tagged	O
+mutations	O
+identified	O
+in	O
+genetic	O
+screens	O
+.	O
+
+Children	O
+with	O
+ADD	O
+showed	O
+an	O
+attenuated	O
+frontal	O
+CNV	O
+-	O
+1	O
+amplitude	O
+and	O
+a	O
+trend	O
+towards	O
+increased	O
+CNV	O
+-	O
+1	O
+and	O
+CNV	O
+-	O
+2	O
+occipital	O
+amplitudes	O
+.	O
+
+Where	O
+UMDNJ	O
+is	O
+headed	O
+.	O
+
+Overexpression	O
+of	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+in	O
+serum	O
+-	O
+starved	O
+human	O
+or	O
+mouse	O
+embryonic	O
+cells	O
+leads	O
+to	O
+apoptosis	O
+which	O
+is	O
+significantly	O
+reduced	O
+in	O
+the	O
+presence	O
+of	O
+growth	O
+factor	O
+-	O
+containing	O
+serum	O
+.	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+-	O
+induced	O
+apoptosis	O
+appears	O
+to	O
+be	O
+deficient	O
+in	O
+bax	B-GENE
+-	O
+null	O
+as	O
+compared	O
+with	O
+bax	B-GENE
+-	O
+wild	O
+-	O
+type	O
+mouse	O
+embryonic	O
+fibroblasts	O
+.	O
+
+METHODS	O
+:	O
+T2	O
+*	O
+-	O
+weighted	O
+,	O
+three	O
+-	O
+dimensional	O
+gradient	O
+-	O
+echo	O
+images	O
+were	O
+acquired	O
+by	O
+exploiting	O
+the	O
+magnetic	O
+susceptibility	O
+difference	O
+between	O
+oxygenated	O
+and	O
+deoxygenated	O
+hemoglobin	B-GENE
+in	O
+the	O
+vasculature	O
+and	O
+microvasculature	O
+.	O
+
+In	O
+the	O
+COPD	O
+patients	O
+,	O
+the	O
+variability	O
+of	O
+Delta	O
+-	O
+inst	O
+Rrs	O
+(	O
+30	O
+%	O
+)	O
+was	O
+greater	O
+than	O
+that	O
+of	O
+FOT	O
+Rrs	O
+(	O
+21	O
+%	O
+)	O
+.	O
+
+Thus	O
+,	O
+Pet111p	B-GENE
+could	O
+play	O
+dual	O
+roles	O
+in	O
+both	O
+membrane	O
+localization	O
+and	O
+regulation	O
+of	O
+Cox2p	B-GENE
+synthesis	O
+within	O
+mitochondria	O
+.	O
+
+The	O
+determination	O
+of	O
+the	O
+double	O
+bounds	O
+in	O
+blood	O
+serum	O
+lipids	O
+by	O
+titration	O
+with	O
+ozone	O
+:	O
+the	O
+pathophysiology	O
+and	O
+diagnostic	O
+significance	O
+]	O
+In	O
+this	O
+article	O
+the	O
+method	O
+of	O
+definition	O
+of	O
+double	O
+binders	O
+in	O
+lipids	O
+of	O
+blood	O
+serum	O
+in	O
+patients	O
+with	O
+different	O
+diseases	O
+basically	O
+atherosclerosis	O
+and	O
+ischemic	O
+heart	O
+disease	O
+,	O
+with	O
+use	O
+titration	O
+by	O
+ozone	O
+is	O
+given	O
+.	O
+
+Ang	B-GENE
+II	I-GENE
+-	O
+induced	O
+fibronectin	B-GENE
+mRNA	O
+was	O
+not	O
+affected	O
+by	O
+PKC	B-GENE
+inhibitors	O
+or	O
+PKC	B-GENE
+depletion	O
+,	O
+whereas	O
+specific	O
+inhibition	O
+of	O
+EGF	B-GENE
+-	I-GENE
+R	I-GENE
+function	O
+by	O
+a	O
+dominant	B-GENE
+negative	I-GENE
+EGF	I-GENE
+-	I-GENE
+R	I-GENE
+mutant	I-GENE
+and	O
+tyrphostin	O
+AG1478	O
+abolished	O
+induction	O
+of	O
+fibronectin	B-GENE
+mRNA	I-GENE
+.	O
+
+Acoust	O
+.	O
+
+Video	O
+images	O
+of	O
+the	O
+nostrils	O
+were	O
+captured	O
+and	O
+then	O
+analyzed	O
+for	O
+area	O
+,	O
+perimeter	O
+,	O
+centroid	O
+,	O
+principal	O
+axis	O
+,	O
+moments	O
+about	O
+the	O
+major	O
+and	O
+minor	O
+axes	O
+(	O
+I11	O
+,	O
+I22	O
+)	O
+,	O
+anisometry	O
+,	O
+bulkiness	O
+,	O
+lateral	O
+offset	O
+,	O
+internostril	O
+angle	O
+,	O
+and	O
+rotational	O
+angle	O
+.	O
+
+Young	O
+fish	O
+(	O
+Oreochromis	O
+mossambicus	O
+)	O
+were	O
+exposed	O
+to	O
+microgravity	O
+(	O
+micro	O
+g	O
+)	O
+for	O
+9	O
+to	O
+10	O
+days	O
+during	O
+space	O
+missions	O
+STS	O
+-	O
+55	O
+and	O
+STS	O
+-	O
+84	O
+,	O
+or	O
+to	O
+hypergravity	O
+(	O
+hg	O
+)	O
+for	O
+9	O
+days	O
+.	O
+
+S6K2	B-GENE
+is	O
+highly	O
+homologous	O
+to	O
+S6K1	B-GENE
+in	O
+the	O
+core	O
+kinase	O
+and	O
+linker	O
+regulatory	O
+domains	O
+but	O
+differs	O
+from	O
+S6K1	B-GENE
+in	O
+the	O
+N	O
+-	O
+and	O
+C	O
+-	O
+terminal	O
+regions	O
+and	O
+is	O
+differently	O
+localized	O
+primarily	O
+to	O
+the	O
+nucleus	O
+because	O
+of	O
+a	O
+C	O
+-	O
+terminal	O
+nuclear	O
+localization	O
+signal	O
+unique	O
+to	O
+S6K2	B-GENE
+.	O
+
+Pretreatment	O
+of	O
+cells	O
+with	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+-	I-GENE
+extracellular	I-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+(	O
+MEK	B-GENE
+)	O
+inhibitor	O
+U0126	O
+inhibited	O
+S6K2	B-GENE
+activation	O
+to	O
+a	O
+greater	O
+extent	O
+than	O
+S6K1	B-GENE
+.	O
+
+T	O
+cells	O
+express	O
+two	O
+isoforms	O
+of	O
+S6k1	B-GENE
+:	O
+a	O
+70	O
+kDa	O
+cytoplasmic	O
+kinase	O
+and	O
+an	O
+85	O
+kDa	O
+isoform	O
+that	O
+has	O
+a	O
+classic	O
+nuclear	O
+localisation	O
+.	O
+
+Ketanserin	O
+,	O
+a	O
+hypotensive	O
+drug	O
+with	O
+5	B-GENE
+-	I-GENE
+HT2	I-GENE
+receptor	I-GENE
+antagonism	O
+,	O
+when	O
+administered	O
+by	O
+topical	O
+infusion	O
+of	O
+a	O
+0	O
+.	O
+25	O
+%	O
+w	O
+/	O
+v	O
+solution	O
+by	O
+corneal	O
+and	O
+scleral	O
+applications	O
+,	O
+was	O
+found	O
+to	O
+lower	O
+intraocular	O
+pressure	O
+with	O
+four	O
+times	O
+more	O
+activity	O
+than	O
+its	O
+metabolite	O
+,	O
+ketanserinol	O
+.	O
+
+A	O
+prospectively	O
+gated	O
+2D	O
+axial	O
+sequence	O
+with	O
+velocity	O
+encoding	O
+in	O
+the	O
+craniocaudal	O
+direction	O
+in	O
+the	O
+cervical	O
+region	O
+was	O
+set	O
+at	O
+a	O
+velocity	O
+of	O
++	O
+/	O
+-	O
+10	O
+cm	O
+/	O
+s	O
+.	O
+
+It	O
+was	O
+subsequently	O
+shown	O
+that	O
+Tip60	B-GENE
+had	O
+histone	B-GENE
+acetyltransferase	I-GENE
+(	O
+HAT	B-GENE
+)	O
+activity	O
+.	O
+
+Our	O
+data	O
+show	O
+that	O
+multiple	O
+MLSN1	B-GENE
+transcripts	I-GENE
+,	O
+both	O
+constitutively	O
+expressed	O
+and	O
+inducible	O
+,	O
+are	O
+present	O
+in	O
+cultured	O
+pigmented	O
+melanoma	O
+cells	O
+,	O
+and	O
+suggest	O
+that	O
+MLSN1	B-GENE
+expression	O
+can	O
+be	O
+regulated	O
+at	O
+the	O
+level	O
+of	O
+both	O
+transcription	O
+and	O
+mRNA	O
+processing	O
+.	O
+
+These	O
+results	O
+also	O
+suggest	O
+the	O
+involvement	O
+of	O
+additional	O
+elements	O
+in	O
+the	O
+UPR	O
+.	O
+
+We	O
+show	O
+that	O
+in	O
+contrast	O
+to	O
+SRC1	B-GENE
+,	O
+direct	O
+binding	O
+of	O
+CBP	B-GENE
+to	O
+the	O
+estrogen	B-GENE
+receptor	I-GENE
+is	O
+weak	O
+,	O
+suggesting	O
+that	O
+SRC1	B-GENE
+functions	O
+primarily	O
+as	O
+an	O
+adaptor	O
+to	O
+recruit	O
+CBP	B-GENE
+and	O
+p300	B-GENE
+.	O
+
+Remarkably	O
+,	O
+a	O
+construct	O
+corresponding	O
+to	O
+residues	O
+631	O
+to	O
+970	O
+,	O
+which	O
+contains	O
+only	O
+the	O
+LXXLL	O
+motifs	O
+and	O
+the	O
+AD1	O
+region	O
+of	O
+SRC1	B-GENE
+,	O
+retained	O
+strong	O
+coactivator	O
+activity	O
+in	O
+our	O
+assays	O
+.	O
+
+Since	O
+MEK	B-GENE
+acts	O
+as	O
+a	O
+cytoplasmic	O
+anchor	O
+for	O
+the	O
+ERKs	B-GENE
+,	O
+the	O
+lack	O
+of	O
+a	O
+MEK	B-GENE
+interaction	O
+resulted	O
+in	O
+the	O
+aberrant	O
+nuclear	O
+localization	O
+of	O
+ERK2	B-GENE
+-	O
+Delta19	B-GENE
+-	I-GENE
+25	I-GENE
+mutants	O
+in	O
+serum	O
+-	O
+starved	O
+cells	O
+.	O
+
+Pmt2	B-GENE
+is	O
+a	O
+member	O
+of	O
+a	O
+six	O
+-	O
+protein	O
+family	O
+in	O
+yeast	O
+that	O
+catalyzes	O
+the	O
+first	O
+step	O
+in	O
+O	O
+mannosylation	O
+of	O
+target	O
+proteins	O
+.	O
+
+Of	O
+the	O
+21	O
+quadrants	O
+positive	O
+in	O
+the	O
+controls	O
+,	O
+17	O
+were	O
+correlated	O
+with	O
+previously	O
+detected	O
+jaw	O
+pathoses	O
+.	O
+
+Four	O
+cases	O
+of	O
+synovial	O
+chondromatosis	O
+are	O
+presented	O
+.	O
+
+Previous	O
+studies	O
+have	O
+shown	O
+that	O
+the	O
+pro	O
+-	O
+inflammatory	O
+cytokines	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+and	O
+interferon	B-GENE
+gamma	I-GENE
+reduce	O
+the	O
+expression	O
+of	O
+the	O
+cystic	B-GENE
+fibrosis	I-GENE
+transmembrane	I-GENE
+conductance	I-GENE
+regulator	I-GENE
+(	O
+CFTR	B-GENE
+)	O
+gene	O
+(	O
+CFTR	B-GENE
+)	O
+in	O
+HT	O
+-	O
+29	O
+and	O
+T84	O
+cells	O
+by	O
+acting	O
+post	O
+-	O
+transcriptionally	O
+.	O
+
+Regulation	O
+of	O
+RhoA	B-GENE
+is	O
+required	O
+to	O
+maintain	O
+adhesion	O
+in	O
+stationary	O
+cells	O
+,	O
+but	O
+is	O
+also	O
+critical	O
+for	O
+cell	O
+spreading	O
+and	O
+migration	O
+[	O
+3	O
+]	O
+.	O
+
+Here	O
+we	O
+show	O
+in	O
+mouse	O
+fibroblasts	O
+stably	O
+transformed	O
+by	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+that	O
+mRNA	O
+and	O
+protein	O
+levels	O
+of	O
+p21	B-GENE
+(	O
+WAF1	B-GENE
+/	O
+CIP1	B-GENE
+)	O
+,	O
+cyclin	B-GENE
+D1	I-GENE
+,	O
+and	O
+cyclin	B-GENE
+E	I-GENE
+are	O
+elevated	O
+.	O
+
+ORFA	O
+and	O
+ccdA	B-GENE
+were	O
+constitutively	O
+cotranscribed	O
+as	O
+determined	O
+by	O
+primer	O
+extension	O
+analysis	O
+.	O
+
+Mouse	B-GENE
+Impact	I-GENE
+is	O
+a	O
+paternally	O
+expressed	O
+gene	O
+encoding	O
+an	O
+evolutionarily	O
+conserved	O
+protein	O
+of	O
+unknown	O
+function	O
+.	O
+
+Coexpression	O
+studies	O
+indicate	O
+that	O
+insulin	B-GENE
+and	O
+PKB	B-GENE
+suppress	O
+transactivation	O
+by	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+,	O
+but	O
+not	O
+C	B-GENE
+/	I-GENE
+EBPalpha	I-GENE
+,	O
+and	O
+that	O
+N	O
+-	O
+terminal	O
+transactivation	O
+domains	O
+in	O
+C	B-GENE
+/	I-GENE
+EBPbeta	I-GENE
+are	O
+required	O
+.	O
+
+Among	O
+eight	O
+graminaceous	O
+species	O
+tested	O
+,	O
+Ids3	B-GENE
+expression	O
+was	O
+observed	O
+only	O
+in	O
+Fe	O
+-	O
+deficient	O
+roots	O
+of	O
+H	O
+.	O
+vulgare	O
+and	O
+Secale	O
+cereale	O
+.	O
+which	O
+not	O
+only	O
+secrete	O
+2	O
+'	O
+-	O
+deoxymugineic	O
+acid	O
+(	O
+DMA	O
+)	O
+,	O
+but	O
+also	O
+mugineic	O
+acid	O
+(	O
+MA	O
+)	O
+and	O
+3	O
+-	O
+epihydroxymugineic	O
+acid	O
+(	O
+epiHMA	O
+,	O
+H	O
+.	O
+vulgare	O
+)	O
+,	O
+and	O
+3	O
+-	O
+hydroxymugineic	O
+acid	O
+(	O
+HMA	O
+,	O
+S	O
+.	O
+cereale	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+high	O
+COUP	B-GENE
+-	I-GENE
+TFI	I-GENE
+expression	O
+impeded	O
+the	O
+neuronal	O
+differentiation	O
+of	O
+P19	O
+cells	O
+induced	O
+with	O
+RA	O
+,	O
+resulting	O
+in	O
+cell	O
+cultures	O
+lacking	O
+neurons	O
+.	O
+
+Because	O
+PET	O
+is	O
+also	O
+useful	O
+for	O
+the	O
+pretreatment	O
+and	O
+follow	O
+-	O
+up	O
+evaluation	O
+,	O
+the	O
+use	O
+of	O
+stereotactic	O
+PET	O
+in	O
+these	O
+patients	O
+can	O
+enable	O
+an	O
+accurate	O
+comparison	O
+of	O
+PET	O
+-	O
+based	O
+metabolic	O
+data	O
+with	O
+MR	O
+-	O
+based	O
+anatomical	O
+data	O
+.	O
+
+Therefore	O
+,	O
+in	O
+our	O
+in	O
+vitro	O
+model	O
+,	O
+the	O
+localization	O
+of	O
+the	O
+mutation	O
+in	O
+the	O
+K	B-GENE
+-	I-GENE
+ras	I-GENE
+gene	I-GENE
+predisposes	O
+to	O
+a	O
+different	O
+level	O
+of	O
+aggressiveness	O
+in	O
+the	O
+transforming	O
+phenotype	O
+.	O
+
+Here	O
+,	O
+we	O
+describe	O
+the	O
+isolation	O
+of	O
+MdPin1	B-GENE
+,	O
+a	O
+Pin1	B-GENE
+homologue	O
+from	O
+the	O
+plant	O
+species	O
+apple	O
+(	O
+Malus	O
+domestica	O
+)	O
+and	O
+show	O
+that	O
+it	O
+has	O
+the	O
+same	O
+phosphorylation	O
+-	O
+specific	O
+substrate	O
+specificity	O
+and	O
+can	O
+be	O
+inhibited	O
+by	O
+juglone	O
+in	O
+vitro	O
+,	O
+as	O
+is	O
+the	O
+case	O
+for	O
+Pin1	B-GENE
+.	O
+
+These	O
+and	O
+other	O
+data	O
+presented	O
+suggest	O
+that	O
+TAg	B-GENE
+'	O
+re	O
+-	O
+models	O
+'	O
+host	O
+cell	O
+transcription	O
+factors	O
+that	O
+are	O
+used	O
+early	O
+in	O
+viral	O
+infection	O
+,	O
+and	O
+thereby	O
+mimics	O
+an	O
+event	O
+that	O
+naturally	O
+occurs	O
+during	O
+transformation	O
+.	O
+
+This	O
+sensitivity	O
+analysis	O
+showed	O
+that	O
+the	O
+practical	O
+limits	O
+of	O
+the	O
+accuracy	O
+of	O
+the	O
+used	O
+screening	O
+test	O
+jeopardize	O
+the	O
+estimation	O
+of	O
+the	O
+true	O
+herd	O
+prevalence	O
+within	O
+reasonable	O
+confidence	O
+limits	O
+,	O
+because	O
+the	O
+within	O
+-	O
+herd	O
+PTB	O
+true	O
+prevalence	O
+was	O
+low	O
+.	O
+For	O
+this	O
+reason	O
+we	O
+augmented	O
+the	O
+herd	O
+specificity	O
+for	O
+herds	O
+with	O
+larger	O
+adult	O
+herd	O
+size	O
+(	O
+>	O
+5	O
+)	O
+.	O
+
+ORFK10	B-GENE
+.	I-GENE
+5	I-GENE
+encodes	O
+a	O
+protein	O
+,	O
+latency	B-GENE
+-	I-GENE
+associated	I-GENE
+nuclear	I-GENE
+antigen	I-GENE
+2	I-GENE
+(	O
+LANA2	B-GENE
+)	O
+,	O
+which	O
+is	O
+expressed	O
+in	O
+KSHV	O
+-	O
+infected	O
+hematopoietic	O
+tissues	O
+,	O
+including	O
+PEL	O
+and	O
+CD	O
+but	O
+not	O
+KS	O
+lesions	O
+.	O
+
+In	O
+Xenopus	O
+,	O
+BMPs	B-GENE
+act	O
+as	O
+epidermal	O
+inducers	O
+and	O
+also	O
+as	O
+negative	O
+regulators	O
+of	O
+neurogenesis	O
+.	O
+
+Presently	O
+four	O
+unique	O
+variants	O
+carrying	O
+distinct	O
+GAF	B-GENE
+sequences	I-GENE
+in	O
+the	O
+N	O
+-	O
+terminal	O
+region	O
+have	O
+been	O
+identified	O
+.	O
+
+Genomic	O
+organization	O
+of	O
+the	O
+human	O
+phosphodiesterase	B-GENE
+PDE11A	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+present	O
+findings	O
+revealed	O
+that	O
+the	O
+rib	B-GENE
+-	I-GENE
+2	I-GENE
+protein	I-GENE
+was	O
+a	O
+unique	O
+alpha1	B-GENE
+,	I-GENE
+4	I-GENE
+-	I-GENE
+N	I-GENE
+-	I-GENE
+acetylglucosaminyltransferase	I-GENE
+involved	O
+in	O
+the	O
+biosynthetic	O
+initiation	O
+and	O
+elongation	O
+of	O
+heparan	O
+sulfate	O
+.	O
+
+Inhibition	O
+of	O
+the	O
+Mek	B-GENE
+/	O
+Erk	B-GENE
+pathway	O
+in	O
+Rat1	O
+/	O
+ras	B-GENE
+cells	O
+,	O
+using	O
+the	O
+Mek	B-GENE
+inhibitor	O
+,	O
+PD98059	O
+,	O
+resulted	O
+in	O
+complete	O
+cytoskeletal	O
+recovery	O
+,	O
+indistinguishable	O
+from	O
+that	O
+induced	O
+by	O
+HR12	O
+.	O
+
+The	O
+transcription	O
+factor	O
+CHOP	B-GENE
+/	O
+GADD153	B-GENE
+gene	O
+is	O
+induced	O
+by	O
+cellular	O
+stress	O
+and	O
+is	O
+involved	O
+in	O
+mediating	O
+apoptosis	O
+.	O
+
+Addition	O
+of	O
+synthetic	O
+tyrosine	O
+-	O
+phosphorylated	O
+peptides	O
+derived	O
+from	O
+betac	O
+cytoplasmic	O
+tyrosines	O
+prior	O
+to	O
+GM	B-GENE
+-	I-GENE
+CSF	I-GENE
+stimulation	O
+inhibited	O
+the	O
+in	O
+vitro	O
+activation	O
+of	O
+STAT5	B-GENE
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURES	O
+:	O
+Percentage	O
+change	O
+in	O
+the	O
+apnea	O
+-	O
+hypopnea	O
+index	O
+(	O
+AHI	O
+;	O
+apnea	O
+events	O
++	O
+hypopnea	O
+events	O
+per	O
+hour	O
+of	O
+sleep	O
+)	O
+and	O
+odds	O
+of	O
+developing	O
+moderate	O
+-	O
+to	O
+-	O
+severe	O
+SDB	O
+(	O
+defined	O
+by	O
+an	O
+AHI	O
+>	O
+or	O
+=	O
+15	O
+events	O
+per	O
+hour	O
+of	O
+sleep	O
+)	O
+,	O
+with	O
+respect	O
+to	O
+change	O
+in	O
+weight	O
+.	O
+
+Paraneoplastic	O
+rheumatic	O
+syndromes	O
+.	O
+
+This	O
+article	O
+reviews	O
+recent	O
+information	O
+on	O
+the	O
+frequency	O
+,	O
+characteristics	O
+,	O
+and	O
+possible	O
+pathogenic	O
+mechanisms	O
+of	O
+the	O
+vasculitides	O
+occurring	O
+in	O
+patients	O
+with	O
+the	O
+main	O
+connective	O
+tissue	O
+diseases	O
+.	O
+
+Tec	B-GENE
+kinase	I-GENE
+signaling	O
+in	O
+T	O
+cells	O
+is	O
+regulated	O
+by	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+and	O
+the	O
+Tec	B-GENE
+pleckstrin	B-GENE
+homology	I-GENE
+domain	I-GENE
+.	O
+
+Current	O
+evidence	O
+for	O
+this	O
+type	O
+of	O
+DNA	O
+supercoiling	O
+-	O
+dependent	O
+transcriptional	O
+coupling	O
+,	O
+based	O
+largely	O
+on	O
+the	O
+in	O
+vivo	O
+activities	O
+of	O
+promoters	O
+contained	O
+in	O
+engineered	O
+DNA	O
+constructs	O
+,	O
+suggests	O
+that	O
+the	O
+transcription	O
+complex	O
+must	O
+be	O
+physically	O
+hindered	O
+to	O
+generate	O
+DNA	O
+supercoils	O
+and	O
+to	O
+prevent	O
+their	O
+diffusion	O
+throughout	O
+the	O
+DNA	O
+duplex	O
+.	O
+
+The	O
+structure	O
+of	O
+the	O
+free	O
+SH2	B-GENE
+domain	I-GENE
+has	O
+been	O
+compared	O
+to	O
+that	O
+of	O
+the	O
+SH2	B-GENE
+complexed	O
+with	O
+a	O
+doubly	O
+phosphorylated	O
+peptide	O
+derived	O
+from	O
+polyomavirus	B-GENE
+middle	I-GENE
+T	I-GENE
+antigen	I-GENE
+(	O
+MT	B-GENE
+)	O
+.	O
+
+We	O
+have	O
+identified	O
+three	O
+binding	O
+sites	O
+for	O
+protein	O
+complexes	O
+:	O
+a	O
+palindrome	O
+,	O
+a	O
+direct	O
+repeat	O
+,	O
+and	O
+a	O
+C	O
++	O
+T	O
+sequence	O
+that	O
+corresponds	O
+to	O
+seven	O
+GAGA	O
+motifs	O
+on	O
+the	O
+transcribed	O
+strand	O
+.	O
+
+Copyright	O
+2000	O
+Academic	O
+Press	O
+.	O
+
+Patients	O
+underwent	O
+pretreatment	O
+cystoscopy	O
+and	O
+detailed	O
+tumor	O
+mapping	O
+,	O
+and	O
+were	O
+treated	O
+with	O
+75	O
+mg	O
+.	O
+/	O
+m	O
+.	O
+2	O
+cisplatin	O
+on	O
+day	O
+1	O
+and	O
+1	O
+gm	O
+.	O
+/	O
+m	O
+.	O
+2	O
+daily	O
+,	O
+5	O
+-	O
+fluorouracil	O
+on	O
+days	O
+1	O
+to	O
+4	O
+and	O
+definitive	O
+radiotherapy	O
+.	O
+
+All	O
+9	O
+untreated	O
+patients	O
+underwent	O
+laparoscopy	O
+,	O
+which	O
+identified	O
+3	O
+intra	O
+-	O
+abdominal	O
+,	O
+3	O
+vanished	O
+and	O
+2	O
+peeping	O
+testes	O
+,	O
+and	O
+1	O
+atrophic	O
+testis	O
+in	O
+the	O
+inguinal	O
+canal	O
+.	O
+
+This	O
+philosophy	O
+was	O
+instituted	O
+for	O
+the	O
+compound	O
+RP	O
+73401	O
+,	O
+a	O
+specific	O
+phosphodiesterase	B-GENE
+IV	I-GENE
+inhibitor	O
+,	O
+that	O
+was	O
+being	O
+developed	O
+simultaneously	O
+for	O
+delivery	O
+by	O
+both	O
+oral	O
+and	O
+pulmonary	O
+routes	O
+of	O
+administration	O
+.	O
+
+Increased	O
+levels	O
+of	O
+anticardiolipin	B-GENE
+immunoglobulin	I-GENE
+G	I-GENE
+may	O
+also	O
+cause	O
+bleeding	O
+.	O
+
+RESULTS	O
+:	O
+Prevalence	O
+of	O
+obesity	O
+(	O
+BMI	O
+SDS	O
+>	O
+2	O
+.	O
+0	O
+)	O
+was	O
+<	O
+2	O
+%	O
+at	O
+diagnosis	O
+,	O
+but	O
+increased	O
+to	O
+16	O
+%	O
+at	O
+3y	O
+.	O
+
+One	O
+of	O
+the	O
+sequelae	O
+of	O
+the	O
+antiphospholipid	O
+-	O
+antibodies	O
+is	O
+an	O
+impaired	O
+uteroplacental	O
+circulation	O
+.	O
+
+Bupropion	O
+to	O
+aid	O
+smoking	O
+cessation	O
+.	O
+
+Using	O
+a	O
+natural	O
+dominant	O
+negative	O
+for	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+transcriptional	O
+activity	O
+in	O
+ROS	O
+17	O
+/	O
+2	O
+.	O
+8	O
+cells	O
+,	O
+we	O
+then	O
+showed	O
+that	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+transcription	I-GENE
+factors	I-GENE
+mediated	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+-	O
+and	O
+BMP	B-GENE
+-	I-GENE
+2	I-GENE
+-	O
+regulated	O
+expression	O
+of	O
+the	O
+(	B-GENE
+alpha1	I-GENE
+)	I-GENE
+collagen	I-GENE
+I	I-GENE
+gene	I-GENE
+as	O
+well	O
+as	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+-	O
+regulated	O
+expression	O
+of	O
+the	O
+parathyroid	B-GENE
+hormone	I-GENE
+(	O
+PTH	B-GENE
+)	O
+/	O
+PTH	B-GENE
+-	I-GENE
+related	I-GENE
+peptide	I-GENE
+(	I-GENE
+PTHrP	I-GENE
+)	I-GENE
+receptor	I-GENE
+.	O
+
+PM	O
+12	O
+or	O
+18	O
+mg	O
+/	O
+kg	O
+daily	O
+plus	O
+a	O
+standard	O
+dose	O
+of	O
+SB	O
+for	O
+21	O
+days	O
+was	O
+statistically	O
+more	O
+effective	O
+than	O
+SB	O
+in	O
+producing	O
+a	O
+final	O
+cure	O
+for	O
+patients	O
+with	O
+VL	O
+in	O
+Bihar	O
+,	O
+India	O
+.	O
+
+There	O
+were	O
+significant	O
+differences	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+between	O
+the	O
+fracture	O
+and	O
+nonfracture	O
+groups	O
+in	O
+the	O
+total	O
+femur	O
+BMD	O
+(	O
+13	O
+%	O
+)	O
+,	O
+trabecular	O
+BMD	O
+in	O
+the	O
+distal	O
+radius	O
+(	O
+4	O
+%	O
+)	O
+,	O
+and	O
+the	O
+fractal	O
+dimension	O
+in	O
+the	O
+radiographs	O
+(	O
+FD2	O
+)	O
+(	O
+3	O
+%	O
+)	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+and	O
+compare	O
+interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+)	O
+levels	O
+in	O
+gingival	O
+crevicular	O
+fluid	O
+(	O
+GCF	O
+)	O
+and	O
+clinical	O
+periodontal	O
+findings	O
+in	O
+patients	O
+with	O
+rheumatoid	O
+arthritis	O
+(	O
+RA	O
+)	O
+and	O
+adult	O
+periodontitis	O
+(	O
+AP	O
+)	O
+.	O
+
+In	O
+a	O
+prospective	O
+,	O
+multicentre	O
+trial	O
+the	O
+efficacy	O
+of	O
+an	O
+Vitex	O
+agnus	O
+castus	O
+L	O
+extract	O
+Ze	O
+440	O
+was	O
+investigated	O
+in	O
+50	O
+patients	O
+with	O
+pre	O
+-	O
+menstrual	O
+syndrome	O
+(	O
+PMS	O
+)	O
+.	O
+
+Studies	O
+are	O
+necessary	O
+to	O
+assess	O
+the	O
+source	O
+of	O
+contamination	O
+and	O
+potential	O
+role	O
+of	O
+MRSA	O
+-	O
+contaminated	O
+milk	O
+in	O
+the	O
+transmission	O
+of	O
+MRSA	O
+to	O
+neonates	O
+.	O
+
+Depending	O
+on	O
+treatment	O
+exposures	O
+,	O
+this	O
+at	O
+-	O
+risk	O
+population	O
+may	O
+experience	O
+life	O
+-	O
+threatening	O
+late	O
+effects	O
+,	O
+such	O
+as	O
+cirrhosis	O
+secondary	O
+to	O
+hepatitis	O
+C	O
+or	O
+late	O
+-	O
+onset	O
+anthracycline	O
+-	O
+induced	O
+cardiomyopathy	O
+,	O
+or	O
+life	O
+-	O
+changing	O
+late	O
+effects	O
+,	O
+such	O
+as	O
+cognitive	O
+dysfunction	O
+.	O
+
+The	O
+presence	O
+of	O
+locus	O
+-	O
+specific	O
+residues	O
+throughout	O
+the	O
+entire	O
+promoter	O
+region	O
+strongly	O
+suggests	O
+that	O
+the	O
+various	O
+HLA	B-GENE
+class	I-GENE
+I	I-GENE
+loci	I-GENE
+are	O
+differentially	O
+regulated	O
+.	O
+
+Because	O
+the	O
+number	O
+of	O
+parameters	O
+required	O
+by	O
+a	O
+Volterra	O
+series	O
+grows	O
+rapidly	O
+with	O
+both	O
+the	O
+length	O
+of	O
+its	O
+memory	O
+and	O
+the	O
+order	O
+of	O
+its	O
+nonlinearity	O
+,	O
+methods	O
+for	O
+identifying	O
+these	O
+models	O
+from	O
+measurements	O
+of	O
+input	O
+/	O
+output	O
+data	O
+are	O
+limited	O
+to	O
+low	O
+-	O
+order	O
+systems	O
+with	O
+relatively	O
+short	O
+memories	O
+.	O
+
+The	O
+standard	O
+method	O
+for	O
+calculating	O
+the	O
+composite	O
+score	O
+on	O
+the	O
+S	O
+-	O
+B	O
+IV	O
+excludes	O
+subtests	O
+with	O
+a	O
+raw	O
+score	O
+of	O
+0	O
+,	O
+which	O
+overestimates	O
+cognitive	O
+functioning	O
+in	O
+young	O
+biologically	O
+high	O
+risk	O
+children	O
+.	O
+
+NiCl	O
+(	O
+2	O
+)	O
+-	O
+induced	O
+MCP	B-GENE
+-	I-GENE
+1	I-GENE
+synthesis	O
+required	O
+activation	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+since	O
+mutation	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+in	O
+the	O
+promoter	O
+resulted	O
+in	O
+complete	O
+loss	O
+of	O
+inducible	O
+promoter	O
+activity	O
+.	O
+
+Engagement	O
+of	O
+human	B-GENE
+CD2	I-GENE
+by	O
+mitogenic	O
+pairs	O
+of	O
+anti	B-GENE
+-	I-GENE
+CD2	I-GENE
+mAb	I-GENE
+induces	O
+tyrosine	O
+phosphorylation	O
+of	O
+a	O
+number	O
+of	O
+intracellular	O
+proteins	O
+including	O
+a	O
+120	O
+kDa	O
+phosphoprotein	O
+that	O
+we	O
+identify	O
+as	O
+the	O
+proto	B-GENE
+-	I-GENE
+oncogene	I-GENE
+c	I-GENE
+-	I-GENE
+Cbl	I-GENE
+.	O
+
+Validity	O
+of	O
+NIR	O
+spectroscopy	O
+for	O
+quantitatively	O
+measuring	O
+muscle	O
+oxidative	O
+metabolic	O
+rate	O
+in	O
+exercise	O
+.	O
+
+Previous	O
+studies	O
+have	O
+demonstrated	O
+that	O
+tissue	O
+-	O
+restricted	O
+transcription	O
+factors	O
+including	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+and	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+interaction	I-GENE
+partner	I-GENE
+(	O
+PIP	B-GENE
+)	O
+function	O
+synergistically	O
+with	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+plus	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+to	O
+stimulate	O
+the	O
+kappaE3	B-GENE
+'	I-GENE
+-	I-GENE
+enhancer	I-GENE
+in	O
+3T3	O
+cells	O
+.	O
+
+The	O
+murine	B-GENE
+int	I-GENE
+-	I-GENE
+6	I-GENE
+locus	I-GENE
+,	O
+identified	O
+as	O
+a	O
+frequent	O
+integration	O
+site	O
+of	O
+mouse	O
+mammary	O
+tumor	O
+viruses	O
+,	O
+encodes	O
+the	O
+48	B-GENE
+-	I-GENE
+kDa	I-GENE
+eIF3e	I-GENE
+subunit	I-GENE
+of	I-GENE
+translation	I-GENE
+initiation	I-GENE
+factor	I-GENE
+eIF3	I-GENE
+.	O
+
+An	O
+int6	B-GENE
+deletion	I-GENE
+(	O
+int6Delta	B-GENE
+)	O
+mutant	O
+was	O
+viable	O
+but	O
+grew	O
+slowly	O
+in	O
+minimal	O
+medium	O
+.	O
+
+We	O
+produced	O
+transgenic	O
+plants	O
+expressing	O
+the	O
+antisense	B-GENE
+Arabidopsis	I-GENE
+HD	I-GENE
+(	O
+AtHD1	B-GENE
+)	O
+gene	O
+.	O
+
+Four	O
+transcription	O
+initiation	O
+sites	O
+have	O
+been	O
+identified	O
+by	O
+full	O
+-	O
+length	O
+RNA	B-GENE
+ligase	I-GENE
+-	O
+mediated	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+(	O
+RLM	O
+-	O
+RACE	O
+)	O
+between	O
+-	O
+61	O
+and	O
+-	O
+32	O
+bp	O
+from	O
+the	O
+translation	O
+initiation	O
+codon	O
+.	O
+Reverse	O
+transcription	O
+-	O
+PCR	O
+analysis	O
+revealed	O
+that	O
+PFK	B-GENE
+-	I-GENE
+A	I-GENE
+,	O
+PFK	B-GENE
+-	I-GENE
+B	I-GENE
+and	O
+PFK	B-GENE
+-	I-GENE
+C	I-GENE
+genes	I-GENE
+were	O
+expressed	O
+,	O
+in	O
+all	O
+mouse	O
+tissues	O
+tested	O
+,	O
+at	O
+varying	O
+levels	O
+.	O
+
+PFK	B-GENE
+-	I-GENE
+A	I-GENE
+mRNA	O
+was	O
+more	O
+abundantly	O
+expressed	O
+in	O
+all	O
+tissues	O
+than	O
+were	O
+the	O
+PFK	B-GENE
+-	I-GENE
+B	I-GENE
+and	O
+PFK	B-GENE
+-	I-GENE
+C	I-GENE
+genes	I-GENE
+.	O
+
+We	O
+used	O
+the	O
+Toshiba	O
+IIDR	O
+system	O
+,	O
+which	O
+is	O
+composed	O
+of	O
+an	O
+X	O
+-	O
+ray	O
+TV	O
+system	O
+and	O
+a	O
+digital	O
+image	O
+managing	O
+circuit	O
+.	O
+
+In	O
+whole	O
+sardine	O
+,	O
+domoic	O
+acid	O
+was	O
+detected	O
+in	O
+levels	O
+exceeding	O
+sometimes	O
+the	O
+regulatory	O
+limit	O
+.	O
+
+Closeup	O
+:	O
+a	O
+resource	O
+for	O
+nurses	O
+who	O
+smoke	O
+.	O
+
+[	O
+18F	O
+]	O
+(	O
++	O
+)	O
+-	O
+4	O
+-	O
+fluorobenzyltrozamicol	O
+(	O
+FBT	O
+)	O
+,	O
+which	O
+selectively	O
+binds	O
+to	O
+the	O
+vesicular	O
+acetylcholine	B-GENE
+transporter	I-GENE
+in	O
+the	O
+presynaptic	O
+cholinergic	O
+neuron	O
+,	O
+has	O
+previously	O
+been	O
+shown	O
+to	O
+be	O
+a	O
+useful	O
+ligand	O
+for	O
+the	O
+study	O
+of	O
+cholinergic	O
+terminal	O
+density	O
+in	O
+the	O
+basal	O
+ganglia	O
+with	O
+PET	O
+.	O
+
+We	O
+demonstrate	O
+that	O
+the	O
+protein	O
+is	O
+a	O
+murine	B-GENE
+homologue	I-GENE
+of	I-GENE
+SAF	I-GENE
+-	I-GENE
+A	I-GENE
+which	O
+has	O
+been	O
+shown	O
+to	O
+bind	O
+selectively	O
+to	O
+MARs	O
+and	O
+is	O
+responsible	O
+for	O
+the	O
+satMa	B-GENE
+-	O
+binding	O
+activity	O
+in	O
+the	O
+chromatographic	O
+fractions	O
+.	O
+
+The	O
+molecular	O
+associations	O
+dictating	O
+INCENP	B-GENE
+behavior	O
+during	O
+mitosis	O
+are	O
+currently	O
+unknown	O
+.	O
+
+Ang	B-GENE
+II	I-GENE
+significantly	O
+induced	O
+Ang2	B-GENE
+mRNA	I-GENE
+accumulations	O
+without	O
+affecting	O
+Ang1	B-GENE
+or	O
+Tie2	B-GENE
+expression	O
+,	O
+which	O
+was	O
+inhibited	O
+by	O
+protein	B-GENE
+kinase	I-GENE
+C	I-GENE
+inhibitors	O
+and	O
+by	O
+intracellular	O
+Ca	O
+(	O
+2	O
++	O
+)	O
+chelating	O
+agents	O
+.	O
+
+Promoter	O
+analysis	O
+demonstrated	O
+that	O
+the	O
+sequence	O
+identical	O
+to	O
+consensus	O
+cAMP	O
+-	O
+responsive	O
+element	O
+(	O
+CRE	O
+)	O
+located	O
+at	O
+-	O
+481	O
+of	O
+the	O
+SMemb	B-GENE
+promoter	I-GENE
+was	O
+critical	O
+for	O
+Hex	B-GENE
+responsiveness	O
+.	O
+
+LH	B-GENE
+/	I-GENE
+CG	I-GENE
+receptor	I-GENE
+activation	O
+of	O
+ARNO	B-GENE
+is	O
+not	O
+mediated	O
+by	O
+activation	O
+of	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+(	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+)	O
+or	O
+by	O
+G	B-GENE
+protein	I-GENE
+beta	I-GENE
+gamma	I-GENE
+subunits	I-GENE
+.	O
+
+Deletion	O
+analysis	O
+showed	O
+that	O
+the	O
+-	O
+321	O
+/	O
++	O
+41	O
+sequence	O
+was	O
+sufficient	O
+for	O
+both	O
+the	O
+constitutive	O
+promoter	O
+activity	O
+and	O
+auto	O
+-	O
+activation	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+identified	O
+the	O
+interaction	O
+of	O
+C	B-GENE
+/	I-GENE
+EBPs	I-GENE
+and	O
+Sp1	B-GENE
+to	O
+this	O
+region	O
+.	O
+
+Termination	O
+of	O
+induced	O
+VT	O
+on	O
+the	O
+first	O
+attempt	O
+was	O
+comparable	O
+with	O
+BV	O
+pacing	O
+(	O
+87	O
+.	O
+4	O
+%	O
+)	O
+versus	O
+RV	O
+pacing	O
+(	O
+89	O
+.	O
+6	O
+%	O
+)	O
+.	O
+
+We	O
+compare	O
+the	O
+results	O
+of	O
+this	O
+algorithm	O
+with	O
+the	O
+results	O
+obtained	O
+with	O
+two	O
+other	O
+algorithms	O
+,	O
+the	O
+optimal	O
+algorithm	O
+for	O
+monochannel	O
+nonoverlapping	O
+noise	O
+and	O
+the	O
+optimal	O
+algorithm	O
+for	O
+multichannel	O
+additive	O
+noise	O
+,	O
+and	O
+we	O
+show	O
+that	O
+in	O
+both	O
+cases	O
+improvement	O
+can	O
+be	O
+obtained	O
+.	O
+
+Changes	O
+in	O
+stimulation	O
+levels	O
+over	O
+time	O
+in	O
+nucleus	O
+22	O
+cochlear	O
+implant	O
+users	O
+.	O
+
+A	O
+marked	O
+decrease	O
+in	O
+the	O
+type	B-GENE
+1	I-GENE
+insulin	I-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	I-GENE
+IGF	I-GENE
+)	I-GENE
+receptor	I-GENE
+(	O
+IGF	B-GENE
+-	I-GENE
+IR	I-GENE
+)	O
+occurs	O
+in	O
+prostate	O
+epithelial	O
+cells	O
+during	O
+transformation	O
+from	O
+the	O
+benign	O
+to	O
+the	O
+metastatic	O
+state	O
+.	O
+
+The	O
+P69	O
+cell	O
+line	O
+was	O
+derived	O
+by	O
+immortalization	O
+of	O
+human	O
+primary	O
+prostate	O
+epithelial	O
+cells	O
+with	O
+simian	B-GENE
+virus	I-GENE
+-	I-GENE
+40	I-GENE
+T	I-GENE
+antigen	I-GENE
+and	O
+is	O
+rarely	O
+tumorigenic	O
+.	O
+
+We	O
+determined	O
+whether	O
+the	O
+human	B-GENE
+StAR	I-GENE
+promoter	I-GENE
+is	O
+responsive	O
+to	O
+sterol	B-GENE
+regulatory	I-GENE
+element	I-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+(	O
+SREBPs	B-GENE
+)	O
+.	O
+
+Expression	O
+of	O
+SREBP	B-GENE
+-	I-GENE
+1a	I-GENE
+stimulated	O
+StAR	B-GENE
+promoter	I-GENE
+activity	O
+in	O
+the	O
+context	O
+of	O
+COS	O
+-	O
+1	O
+cells	O
+and	O
+human	O
+granulosa	O
+-	O
+lutein	O
+cells	O
+.	O
+
+Because	O
+the	O
+high	B-GENE
+-	I-GENE
+density	I-GENE
+lipoprotein	I-GENE
+receptor	I-GENE
+(	O
+HDL	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+is	O
+a	O
+key	O
+element	O
+in	O
+cholesterol	O
+homeostasis	O
+and	O
+a	O
+potential	O
+therapeutic	O
+target	O
+for	O
+hypercholesterolemic	O
+drugs	O
+,	O
+an	O
+understanding	O
+of	O
+HDL	B-GENE
+-	I-GENE
+R	I-GENE
+regulation	O
+is	O
+essential	O
+.	O
+
+IFN	B-GENE
+-	I-GENE
+stimulated	I-GENE
+gene	I-GENE
+factor	I-GENE
+-	I-GENE
+3	I-GENE
+and	O
+STAT1	B-GENE
+homodimers	I-GENE
+formed	O
+and	O
+bound	O
+an	O
+IFN	B-GENE
+-	I-GENE
+stimulated	I-GENE
+response	I-GENE
+element	I-GENE
+(	O
+ISRE	B-GENE
+)	O
+and	O
+gamma	B-GENE
+-	I-GENE
+activated	I-GENE
+sequence	I-GENE
+(	O
+GAS	B-GENE
+)	O
+element	O
+,	O
+respectively	O
+.	O
+
+We	O
+have	O
+therefore	O
+studied	O
+the	O
+molecular	O
+mechanisms	O
+of	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+action	O
+on	O
+thyroglobulin	B-GENE
+(	O
+TG	B-GENE
+)	O
+gene	O
+expression	O
+by	O
+focusing	O
+our	O
+attention	O
+on	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+regulation	O
+of	O
+thyroid	O
+-	O
+specific	O
+transcription	O
+factors	O
+.	O
+
+The	O
+epitope	O
+-	O
+protected	O
+lysine	O
+(	O
+K	O
+)	O
+was	O
+present	O
+in	O
+a	O
+30	B-GENE
+-	I-GENE
+aa	I-GENE
+TPO	I-GENE
+fragment	I-GENE
+that	O
+,	O
+by	O
+N	O
+-	O
+terminal	O
+sequencing	O
+,	O
+was	O
+found	O
+to	O
+be	O
+K713	O
+.	O
+
+To	O
+understand	O
+the	O
+molecular	O
+regulation	O
+of	O
+these	O
+genes	O
+in	O
+thyroid	O
+cells	O
+,	O
+the	O
+effect	O
+of	O
+thyroid	B-GENE
+transcription	I-GENE
+factor	I-GENE
+1	I-GENE
+(	O
+TTF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+and	O
+the	O
+paired	B-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+protein	I-GENE
+8	I-GENE
+(	O
+Pax	B-GENE
+-	I-GENE
+8	I-GENE
+)	O
+on	O
+the	O
+transcriptional	O
+activity	O
+of	O
+the	O
+deiodinase	B-GENE
+promoters	I-GENE
+were	O
+studied	O
+.	O
+
+Regional	O
+blood	O
+blow	O
+was	O
+measured	O
+by	O
+means	O
+of	O
+microspheres	O
+in	O
+predefined	O
+regions	O
+of	O
+the	O
+C6	O
+,	O
+T11	O
+,	O
+and	O
+L6	O
+vertebrae	O
+.	O
+
+Activation	O
+of	O
+transcription	O
+through	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+site	I-GENE
+in	O
+Jurkat	O
+cells	O
+by	O
+JunD	B-GENE
+and	O
+/	O
+or	O
+Fra	B-GENE
+-	I-GENE
+2	I-GENE
+was	O
+weak	O
+.	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+,	O
+JunB	B-GENE
+,	O
+and	O
+c	B-GENE
+-	I-GENE
+Fos	I-GENE
+activation	O
+was	O
+greater	O
+,	O
+although	O
+the	O
+level	O
+was	O
+still	O
+less	O
+than	O
+that	O
+with	O
+Tax	B-GENE
+.	O
+
+The	O
+mechanism	O
+of	O
+ligand	O
+-	O
+activated	O
+estrogen	B-GENE
+receptor	I-GENE
+alpha	I-GENE
+(	O
+ERalpha	B-GENE
+)	O
+-	O
+dependent	O
+activation	O
+of	O
+gene	O
+expression	O
+through	O
+the	O
+SRE	O
+was	O
+determined	O
+by	O
+mutational	O
+analysis	O
+of	O
+the	O
+promoter	O
+,	O
+analysis	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	O
+MAPK	B-GENE
+)	O
+pathway	O
+activation	O
+by	O
+E2	O
+,	O
+and	O
+transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+alpha	I-GENE
+(	O
+TGF	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+as	O
+a	O
+positive	O
+control	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Under	O
+current	O
+immunization	O
+practices	O
+,	O
+the	O
+authors	O
+estimate	O
+that	O
+nearly	O
+13	O
+,	O
+000	O
+Asian	O
+and	O
+Pacific	O
+Islander	O
+children	O
+living	O
+in	O
+the	O
+United	O
+States	O
+today	O
+will	O
+become	O
+infected	O
+with	O
+HBV	O
+in	O
+the	O
+future	O
+,	O
+resulting	O
+in	O
+more	O
+than	O
+600	O
+liver	O
+carcinoma	O
+deaths	O
+.	O
+
+We	O
+observed	O
+NP	B-GENE
+/	O
+NMP4	B-GENE
+/	O
+CIZ	B-GENE
+expression	O
+in	O
+osteocytes	O
+,	O
+osteoblasts	O
+,	O
+and	O
+chondrocytes	O
+in	O
+rat	O
+bone	O
+.	O
+
+Chlamydia	O
+and	O
+cervical	O
+cancer	O
+:	O
+a	O
+real	O
+association	O
+?	O
+
+A	O
+novel	O
+approach	O
+was	O
+developed	O
+for	O
+identifying	O
+transcription	O
+factor	O
+activities	O
+associated	O
+with	O
+NGF	B-GENE
+-	O
+activated	O
+,	O
+but	O
+not	O
+EGF	B-GENE
+-	O
+activated	O
+,	O
+signaling	O
+,	O
+using	O
+random	O
+oligonucleotide	O
+clones	O
+from	O
+a	O
+DNA	O
+recognition	O
+library	O
+to	O
+isolate	O
+specific	O
+DNA	O
+binding	O
+proteins	O
+from	O
+PC12	O
+nuclear	O
+extracts	O
+.	O
+
+NGF	B-GENE
+elicits	O
+a	O
+more	O
+delayed	O
+and	O
+sustained	O
+ERK	B-GENE
+phosphorylation	O
+than	O
+EGF	B-GENE
+,	O
+consistent	O
+with	O
+previous	O
+reports	O
+.	O
+
+NGF	B-GENE
+,	O
+but	O
+not	O
+EGF	B-GENE
+,	O
+enhances	O
+the	O
+upper	O
+bands	O
+,	O
+corresponding	O
+to	O
+phosphorylated	B-GENE
+Fra	I-GENE
+-	I-GENE
+2	I-GENE
+.	O
+
+The	O
+actA	B-GENE
+gene	I-GENE
+is	O
+present	O
+as	O
+a	O
+single	O
+copy	O
+in	O
+the	O
+genome	O
+of	O
+A	O
+.	O
+chrysogenum	O
+;	O
+and	O
+its	O
+expression	O
+level	O
+,	O
+opposite	O
+to	O
+pcbC	B-GENE
+and	O
+cefEF	B-GENE
+cephalosporin	I-GENE
+biosynthetic	I-GENE
+genes	I-GENE
+,	O
+was	O
+steady	O
+during	O
+cephalosporin	O
+fermentation	O
+,	O
+showing	O
+a	O
+single	O
+1	O
+.	O
+4	O
+-	O
+kb	O
+transcript	O
+.	O
+
+Adding	O
+10	O
+mmol	O
+SDS	O
+/	O
+l	O
+led	O
+to	O
+transient	O
+inhibition	O
+of	O
+acidification	O
+,	O
+metal	O
+solubilization	O
+and	O
+sulfur	O
+oxidation	O
+.	O
+
+We	O
+have	O
+investigated	O
+the	O
+role	O
+of	O
+NGF	B-GENE
+in	O
+regulating	O
+gene	O
+transcription	O
+in	O
+PC12	O
+and	O
+INS	O
+-	O
+1	O
+cells	O
+,	O
+in	O
+order	O
+to	O
+define	O
+if	O
+there	O
+are	O
+NGF	B-GENE
+-	O
+regulated	O
+genes	O
+per	O
+se	O
+.	O
+
+Nine	O
+animals	O
+served	O
+as	O
+control	O
+animals	O
+,	O
+whereas	O
+20	O
+animals	O
+received	O
+a	O
+focal	O
+arachnoid	O
+scar	O
+at	O
+C1	O
+-	O
+C2	O
+,	O
+which	O
+was	O
+produced	O
+by	O
+placement	O
+of	O
+a	O
+kaolin	O
+-	O
+soaked	O
+fibrin	B-GENE
+sponge	O
+on	O
+the	O
+posterior	O
+surface	O
+of	O
+the	O
+spinal	O
+cord	O
+.	O
+
+The	O
+Schistosoma	B-GENE
+mansoni	I-GENE
+homologue	I-GENE
+(	O
+SmSmad2	B-GENE
+)	O
+was	O
+overexpressed	O
+in	O
+bacteria	O
+as	O
+a	O
+Sj26	B-GENE
+-	O
+GST	B-GENE
+fusion	O
+protein	O
+and	O
+used	O
+to	O
+raise	O
+specific	O
+antibodies	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+SmSmad2	B-GENE
+responds	O
+to	O
+the	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+signals	O
+by	O
+interaction	O
+with	O
+receptor	B-GENE
+I	I-GENE
+,	O
+which	O
+phosphorylates	O
+it	O
+,	O
+whereupon	O
+it	O
+translocates	O
+into	O
+the	O
+nucleus	O
+presumably	O
+to	O
+regulate	O
+target	O
+gene	O
+transcription	O
+and	O
+consequently	O
+elicit	O
+a	O
+specific	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+effect	O
+.	O
+
+Intact	O
+Flag	O
+-	O
+tagged	O
+protein	O
+products	O
+from	O
+all	O
+six	O
+were	O
+produced	O
+from	O
+genomic	O
+expression	O
+vectors	O
+,	O
+although	O
+the	O
+ORF40	O
+/	O
+41	O
+transcript	O
+encoding	O
+a	O
+primase	B-GENE
+-	O
+helicase	B-GENE
+component	O
+proved	O
+to	O
+be	O
+spliced	O
+with	O
+a	O
+127	O
+-	O
+bp	O
+intron	O
+.	O
+
+Expression	O
+of	O
+the	O
+src	B-GENE
+homology	I-GENE
+3	I-GENE
+(	O
+SH3	B-GENE
+)	O
+-	O
+encoding	O
+,	O
+expressed	O
+in	O
+tumorigenic	O
+astrocytes	O
+(	O
+SETA	B-GENE
+)	O
+gene	O
+is	O
+associated	O
+with	O
+astrocyte	O
+transformation	O
+in	O
+culture	O
+and	O
+tumors	O
+in	O
+the	O
+adult	O
+brain	O
+.	O
+
+METHODS	O
+:	O
+One	O
+hundred	O
+fourteen	O
+consecutive	O
+patients	O
+(	O
+mean	O
+age	O
+61	O
+years	O
+)	O
+with	O
+focal	O
+pancreatic	O
+masses	O
+,	O
+detected	O
+on	O
+CT	O
+,	O
+underwent	O
+EUS	O
+-	O
+FNA	O
+by	O
+using	O
+a	O
+linear	O
+-	O
+array	O
+echoendoscope	O
+and	O
+22	O
+-	O
+gauge	O
+needles	O
+.	O
+
+METHODS	O
+:	O
+Thyroid	O
+status	O
+was	O
+measured	O
+at	O
+baseline	O
+(	O
+1990	O
+-	O
+93	O
+)	O
+,	O
+through	O
+assessment	O
+of	O
+serum	O
+antibodies	O
+to	O
+thyroid	B-GENE
+peroxidase	I-GENE
+(	O
+TPO	B-GENE
+-	I-GENE
+Abs	I-GENE
+,	O
+positive	O
+:	O
+>	O
+10	O
+IU	O
+/	O
+ml	O
+)	O
+,	O
+serum	B-GENE
+TSH	I-GENE
+levels	O
+,	O
+and	O
+when	O
+TSH	B-GENE
+was	O
+abnormal	O
+(	O
+<	O
+0	O
+.	O
+4	O
+or	O
+>	O
+4	O
+.	O
+0	O
+mU	O
+/	O
+l	O
+)	O
+,	O
+serum	B-GENE
+thyroxin	I-GENE
+levels	O
+(	O
+T4	O
+)	O
+.	O
+
+We	O
+suggest	O
+that	O
+ventriculopleural	O
+shunting	O
+should	O
+be	O
+considered	O
+as	O
+the	O
+preferred	O
+alternative	O
+to	O
+peritoneal	O
+drainage	O
+in	O
+children	O
+with	O
+intra	O
+-	O
+abdominal	O
+adhesions	O
+or	O
+with	O
+a	O
+history	O
+of	O
+recent	O
+peritoneal	O
+infection	O
+.	O
+
+TBARS	O
+levels	O
+,	O
+oxygen	O
+-	O
+radical	O
+absorbing	O
+capacity	O
+assay	O
+and	O
+AFR	O
+release	O
+assessed	O
+by	O
+electron	O
+paramagnetic	O
+resonance	O
+(	O
+EPR	O
+)	O
+were	O
+used	O
+to	O
+explore	O
+the	O
+existence	O
+of	O
+oxidative	O
+stress	O
+in	O
+diabetes	O
+.	O
+
+Long	O
+-	O
+range	O
+comparison	O
+of	O
+human	B-GENE
+and	I-GENE
+mouse	I-GENE
+SCL	I-GENE
+loci	I-GENE
+:	O
+localized	O
+regions	O
+of	O
+sensitivity	O
+to	O
+restriction	O
+endonucleases	O
+correspond	O
+precisely	O
+with	O
+peaks	O
+of	O
+conserved	O
+noncoding	O
+sequences	O
+.	O
+
+To	O
+account	O
+for	O
+this	O
+observation	O
+,	O
+other	O
+possible	O
+causes	O
+include	O
+increased	O
+CSF	O
+pulsation	O
+in	O
+children	O
+creating	O
+motion	O
+artifact	O
+,	O
+changes	O
+in	O
+arterial	O
+oxygen	O
+concentration	O
+intrinsic	O
+to	O
+propofol	O
+or	O
+related	O
+to	O
+the	O
+supplemental	O
+oxygen	O
+normally	O
+administered	O
+,	O
+or	O
+changes	O
+in	O
+CSF	O
+protein	O
+levels	O
+related	O
+to	O
+propofol	O
+binding	O
+to	O
+proteins	O
+for	O
+uptake	O
+into	O
+CSF	O
+.	O
+
+The	O
+utilities	O
+measured	O
+in	O
+our	O
+study	O
+can	O
+be	O
+applied	O
+directly	O
+to	O
+quality	O
+-	O
+of	O
+-	O
+life	O
+determinations	O
+in	O
+clinical	O
+trials	O
+of	O
+adjuvant	O
+IFN	B-GENE
+alpha	I-GENE
+-	I-GENE
+2b	I-GENE
+to	O
+measure	O
+the	O
+net	O
+benefit	O
+of	O
+therapy	O
+.	O
+
+Serum	B-GENE
+PTH	I-GENE
+tended	O
+to	O
+increase	O
+in	O
+the	O
+WL	O
+group	O
+but	O
+not	O
+in	O
+the	O
+WM	O
+group	O
+(	O
+P	O
+<	O
+0	O
+.	O
+06	O
+)	O
+.	O
+
+Structure	O
+of	O
+the	O
+EMAPII	B-GENE
+domain	I-GENE
+of	O
+human	B-GENE
+aminoacyl	I-GENE
+-	I-GENE
+tRNA	I-GENE
+synthetase	I-GENE
+complex	I-GENE
+reveals	O
+evolutionary	O
+dimer	O
+mimicry	O
+.	O
+
+METHODS	O
+:	O
+The	O
+passive	O
+and	O
+active	O
+transport	O
+of	O
+fluorescein	O
+through	O
+the	O
+BRB	O
+was	O
+quantitated	O
+by	O
+vitreous	O
+fluorometry	O
+.	O
+
+Nerve	B-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+NGF	B-GENE
+)	O
+and	O
+retinoic	O
+acid	O
+(	O
+RA	O
+)	O
+exert	O
+important	O
+actions	O
+on	O
+PC12	O
+cells	O
+.	O
+
+The	O
+region	O
+containing	O
+both	O
+serines	O
+is	O
+homologous	O
+to	O
+the	O
+N	O
+-	O
+terminal	O
+destruction	O
+box	O
+of	O
+IkappaBalpha	B-GENE
+,	I-GENE
+-	I-GENE
+beta	I-GENE
+,	I-GENE
+and	I-GENE
+-	I-GENE
+epsilon	I-GENE
+.	O
+
+This	O
+function	O
+requires	O
+not	O
+only	O
+the	O
+kinase	O
+domain	O
+of	O
+Csk	B-GENE
+,	O
+but	O
+also	O
+its	O
+Src	B-GENE
+homology	I-GENE
+3	I-GENE
+(	O
+SH3	B-GENE
+)	O
+and	O
+SH2	B-GENE
+regions	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+showed	O
+that	O
+ERSF	B-GENE
+including	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+and	O
+ATF6alpha	B-GENE
+and	I-GENE
+/	I-GENE
+or	I-GENE
+beta	I-GENE
+and	O
+capable	O
+of	O
+binding	O
+to	O
+ERSE	O
+is	O
+indeed	O
+formed	O
+when	O
+the	O
+cellular	O
+UPR	O
+is	O
+activated	O
+.	O
+
+These	O
+effects	O
+were	O
+not	O
+seen	O
+with	O
+SHIP2	B-GENE
+possessing	O
+a	O
+mutation	O
+in	O
+the	O
+SH2	B-GENE
+domain	I-GENE
+(	O
+R47G	B-GENE
+)	O
+.	O
+
+The	O
+gonadotrope	O
+-	O
+specific	O
+and	O
+regulated	O
+expression	O
+of	O
+the	O
+GnRH	B-GENE
+receptor	I-GENE
+(	O
+GnRH	B-GENE
+-	I-GENE
+R	I-GENE
+)	O
+gene	O
+is	O
+dependent	O
+on	O
+multiple	O
+transcription	O
+factors	O
+that	O
+interact	O
+with	O
+the	O
+noncanonical	B-GENE
+GnRH	I-GENE
+-	I-GENE
+R	I-GENE
+activating	I-GENE
+sequence	I-GENE
+(	O
+GRAS	B-GENE
+)	O
+,	O
+the	O
+activator	B-GENE
+protein	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+element	O
+,	O
+and	O
+the	O
+steroidogenic	B-GENE
+factor	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+binding	O
+site	O
+.	O
+
+METHODS	O
+:	O
+A	O
+structured	O
+interview	O
+was	O
+undertaken	O
+at	O
+the	O
+time	O
+of	O
+initial	O
+consultation	O
+and	O
+at	O
+subsequent	O
+1	O
+-	O
+year	O
+intervals	O
+regarding	O
+type	O
+of	O
+BHS	O
+,	O
+frequency	O
+of	O
+spells	O
+,	O
+associated	O
+phenomenon	O
+,	O
+sequelae	O
+,	O
+family	O
+history	O
+,	O
+and	O
+age	O
+at	O
+termination	O
+of	O
+spells	O
+.	O
+
+In	O
+three	O
+cases	O
+(	O
+21	O
+.	O
+4	O
+%	O
+)	O
+,	O
+the	O
+MR	O
+imaging	O
+was	O
+interpreted	O
+as	O
+negative	O
+,	O
+but	O
+microscopic	O
+tumor	O
+was	O
+shown	O
+around	O
+seroma	O
+on	O
+reexcision	O
+.	O
+
+Methylation	O
+at	O
+both	O
+cytosine	O
+residues	O
+in	O
+the	O
+E2F	B-GENE
+element	O
+(	O
+(	O
+m	O
+)	O
+CG	O
+(	O
+m	O
+)	O
+CG	O
+)	O
+generated	O
+a	O
+new	O
+methylcytosine	O
+-	O
+specific	O
+DNA	O
+-	O
+protein	O
+complex	O
+.	O
+
+These	O
+mutations	O
+,	O
+when	O
+placed	O
+in	O
+a	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+fliF	I-GENE
+background	O
+,	O
+had	O
+no	O
+mutant	O
+phenotype	O
+.	O
+
+As	O
+well	O
+,	O
+IFN	B-GENE
+-	I-GENE
+gamma	I-GENE
+-	O
+induced	O
+expression	O
+of	O
+IRF	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+its	O
+binding	O
+to	O
+the	O
+IRF	B-GENE
+element	I-GENE
+is	O
+inhibited	O
+.	O
+
+This	O
+molecule	O
+,	O
+wH22xeGFP	B-GENE
+,	O
+consists	O
+of	O
+the	O
+entire	B-GENE
+humanized	I-GENE
+anti	I-GENE
+-	I-GENE
+FcgammaRI	I-GENE
+mAb	I-GENE
+H22	B-GENE
+with	O
+eGFP	B-GENE
+genetically	O
+fused	O
+to	O
+the	O
+C	O
+-	O
+terminal	O
+end	O
+of	O
+each	O
+CH3	B-GENE
+domain	I-GENE
+.	O
+wH22xeGFP	B-GENE
+binds	O
+within	O
+the	O
+ligand	O
+-	O
+binding	O
+region	O
+by	O
+its	O
+Fc	B-GENE
+end	O
+,	O
+as	O
+well	O
+as	O
+outside	O
+the	O
+ligand	O
+-	O
+binding	O
+region	O
+by	O
+its	O
+Fab	B-GENE
+ends	O
+,	O
+thereby	O
+cross	O
+-	O
+linking	O
+FcgammaRI	B-GENE
+.	O
+
+This	O
+interaction	O
+is	O
+reciprocal	O
+,	O
+since	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+dimer	I-GENE
+binding	O
+to	O
+a	O
+strong	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+site	I-GENE
+leads	O
+to	O
+enhanced	O
+CREB	B-GENE
+-	I-GENE
+1	I-GENE
+recruitment	O
+to	O
+ATF	B-GENE
+/	O
+CREB	B-GENE
+sites	O
+that	O
+are	O
+weakly	O
+bound	O
+by	O
+CREB	B-GENE
+.	O
+
+The	O
+metabolic	O
+events	O
+occurring	O
+at	O
+or	O
+near	O
+that	O
+structure	O
+and	O
+involving	O
+cyclin	B-GENE
+D3	I-GENE
+cause	O
+the	O
+translocation	O
+of	O
+ICP0	B-GENE
+to	O
+the	O
+cytoplasm	O
+.	O
+
+Transient	O
+transfections	O
+showed	O
+that	O
+a	O
+single	O
+mutation	O
+(	O
+556M	O
+)	O
+decreased	O
+TBLV	B-GENE
+enhancer	I-GENE
+activity	O
+at	O
+least	O
+20	O
+-	O
+fold	O
+in	O
+two	O
+different	O
+T	O
+-	O
+cell	O
+lines	O
+.	O
+
+Vector	O
+stocks	O
+containing	O
+envelope	B-GENE
+proteins	I-GENE
+from	O
+three	O
+different	O
+SIVmac	O
+clones	O
+,	O
+namely	O
+,	O
+SIVmac239	O
+(	O
+T	O
+-	O
+lymphocyte	O
+tropic	O
+[	O
+T	O
+-	O
+tropic	O
+]	O
+)	O
+,	O
+SIVmac316	O
+(	O
+macrophage	O
+tropic	O
+[	O
+M	O
+-	O
+tropic	O
+]	O
+)	O
+,	O
+and	O
+SIVmac1A11	O
+(	O
+dualtropic	O
+)	O
+,	O
+were	O
+tested	O
+.	O
+
+Quantitative	O
+PCR	O
+studies	O
+indicated	O
+that	O
+synthesis	O
+and	O
+transport	O
+of	O
+vector	O
+DNA	O
+into	O
+the	O
+nucleus	O
+were	O
+similar	O
+for	O
+macrophages	O
+infected	O
+with	O
+the	O
+clone	O
+239	O
+and	O
+316	O
+pseudotypes	O
+,	O
+suggesting	O
+that	O
+the	O
+restriction	O
+for	O
+SIVmac239	O
+infection	O
+is	O
+after	O
+reverse	O
+transcription	O
+and	O
+nuclear	O
+import	O
+of	O
+viral	O
+DNA	O
+.	O
+
+Thus	O
+,	O
+the	O
+anti	B-GENE
+-	I-GENE
+interferon	I-GENE
+functions	O
+of	O
+vIRF	B-GENE
+-	I-GENE
+2	I-GENE
+may	O
+contribute	O
+to	O
+the	O
+establishment	O
+of	O
+a	O
+chronic	O
+or	O
+latent	O
+infection	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+activity	O
+of	O
+IkappaB	B-GENE
+kinase	I-GENE
+(	O
+IKK	B-GENE
+-	I-GENE
+beta	I-GENE
+)	O
+,	O
+which	O
+plays	O
+an	O
+essential	O
+role	O
+in	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activation	O
+through	O
+IkappaB	B-GENE
+phosphorylation	O
+,	O
+was	O
+largely	O
+enhanced	O
+in	O
+paclitaxel	O
+-	O
+treated	O
+cells	O
+,	O
+detected	O
+as	O
+IkappaBalpha	B-GENE
+phosphorylation	O
+.	O
+
+We	O
+propose	O
+that	O
+TFOs	O
+represent	O
+a	O
+therapeutic	O
+potential	O
+to	O
+specifically	O
+diminish	O
+the	O
+expression	O
+of	O
+c	B-GENE
+-	I-GENE
+sis	I-GENE
+/	O
+PDGF	B-GENE
+-	I-GENE
+B	I-GENE
+proto	O
+-	O
+oncogene	O
+in	O
+various	O
+pathologic	O
+settings	O
+where	O
+constitutive	O
+expression	O
+of	O
+this	O
+gene	O
+has	O
+been	O
+observed	O
+.	O
+
+Rapid	O
+evolution	O
+of	O
+the	O
+DNA	O
+-	O
+binding	O
+site	O
+in	O
+LAGLIDADG	B-GENE
+homing	I-GENE
+endonucleases	I-GENE
+.	O
+
+Copyright	O
+2001	O
+Academic	O
+Press	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+similarities	O
+with	O
+the	O
+endophilin	B-GENE
+proteins	I-GENE
+cover	O
+the	O
+entire	O
+sequence	O
+of	O
+the	O
+SH3GLB	B-GENE
+family	I-GENE
+,	O
+suggesting	O
+a	O
+common	O
+fold	O
+and	O
+presumably	O
+a	O
+common	O
+mode	O
+of	O
+action	O
+.	O
+
+Mental	O
+rotation	O
+of	O
+paired	O
+figures	O
+engendered	O
+activation	O
+in	O
+the	O
+left	O
+superior	O
+parietal	O
+lobule	O
+and	O
+the	O
+right	O
+frontal	O
+medial	O
+gyrus	O
+.	O
+
+We	O
+also	O
+reported	O
+the	O
+identification	O
+of	O
+three	O
+corresponding	O
+alternative	O
+first	O
+exons	O
+and	O
+an	O
+intronic	O
+promoter	O
+in	O
+the	O
+human	B-GENE
+PDE5A	I-GENE
+gene	I-GENE
+.	O
+
+The	O
+glucose	O
+/	O
+insulin	B-GENE
+stimulation	O
+was	O
+inhibited	O
+by	O
+the	O
+addition	O
+of	O
+polyunsaturated	O
+fatty	O
+acids	O
+.	O
+
+In	O
+the	O
+present	O
+work	O
+,	O
+the	O
+complete	O
+genome	O
+sequences	O
+of	O
+Pyrococcus	O
+horikoshii	O
+and	O
+Pyrococcus	O
+abyssi	O
+,	O
+two	O
+species	O
+in	O
+a	O
+genus	O
+of	O
+hyperthermophilic	O
+archaeon	O
+(	O
+archaebacterium	O
+)	O
+,	O
+were	O
+compared	O
+to	O
+detect	O
+large	O
+genome	O
+polymorphisms	O
+linked	O
+with	O
+restriction	O
+-	O
+modification	O
+gene	O
+homologs	O
+.	O
+
+This	O
+animal	O
+model	O
+of	O
+dystonia	O
+appears	O
+to	O
+be	O
+a	O
+model	O
+of	O
+NAD	O
+in	O
+man	O
+from	O
+the	O
+viewpoint	O
+of	O
+treatment	O
+-	O
+response	O
+.	O
+
+Peripheral	O
+and	O
+preemptive	O
+opioid	O
+antinociception	O
+in	O
+a	O
+mouse	O
+visceral	O
+pain	O
+model	O
+.	O
+
+Twenty	O
+-	O
+six	O
+(	O
+55	O
+%	O
+)	O
+(	O
+95	O
+%	O
+CI	O
+,	O
+41	O
+-	O
+69	O
+%	O
+)	O
+patients	O
+experienced	O
+>	O
+or	O
+=	O
+grade	O
+3	O
+acute	O
+toxicity	O
+(	O
+RTOG	O
+)	O
+.	O
+
+No	O
+'	O
+TATA	O
+'	O
+motif	O
+was	O
+identified	O
+near	O
+either	O
+the	O
+GABPalpha	B-GENE
+or	O
+ATPsynCF6	B-GENE
+transcription	O
+start	O
+sites	O
+.	O
+
+Significantly	O
+higher	O
+lung	O
+function	O
+parameters	O
+were	O
+obtained	O
+in	O
+extubated	O
+recipients	O
+of	O
+LPD	O
+preserved	O
+grafts	O
+2	O
+weeks	O
+after	O
+TX	O
+.	O
+
+Acquired	O
+antithrombin	B-GENE
+deficiency	O
+in	O
+sepsis	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+have	O
+isolated	O
+a	O
+genomic	O
+fragment	O
+containing	O
+the	O
+most	O
+distal	O
+5	O
+'	O
+sequences	O
+of	O
+the	O
+major	O
+GGT	B-GENE
+mRNA	I-GENE
+in	O
+HepG2	O
+cells	O
+.	O
+
+(	O
+1997	O
+)	O
+Nature	O
+387	O
+,	O
+370	O
+-	O
+376	O
+)	O
+]	O
+,	O
+we	O
+suggest	O
+that	O
+the	O
+metal	O
+fluoride	O
+ions	O
+replaced	O
+phosphate	O
+at	O
+the	O
+two	O
+ATP	O
+-	O
+binding	O
+sites	O
+of	O
+the	O
+iron	O
+protein	O
+,	O
+Kp2	B-GENE
+.	O
+
+Expression	O
+of	O
+herpes	B-GENE
+simplex	I-GENE
+virus	I-GENE
+type	I-GENE
+2	I-GENE
+US3	I-GENE
+affects	O
+the	O
+Cdc42	B-GENE
+/	O
+Rac	B-GENE
+pathway	O
+and	O
+attenuates	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+activation	O
+.	O
+
+If	O
+you	O
+think	O
+education	O
+is	O
+expensive	O
+-	O
+-	O
+try	O
+ignorance	O
+-	O
+-	O
+Bok	O
+'	O
+s	O
+Law	O
+.	O
+
+To	O
+study	O
+the	O
+in	O
+vivo	O
+role	O
+of	O
+p16	B-GENE
+.	I-GENE
+7	I-GENE
+,	O
+a	O
+phi29	O
+mutant	O
+containing	O
+a	O
+suppressible	O
+mutation	O
+in	O
+gene	B-GENE
+16	I-GENE
+.	I-GENE
+7	I-GENE
+was	O
+constructed	O
+.	O
+
+To	O
+the	O
+best	O
+of	O
+our	O
+knowledge	O
+,	O
+SNTCS	O
+is	O
+highly	O
+malignant	O
+.	O
+
+The	O
+extraordinary	O
+stability	O
+of	O
+peptide	B-GENE
+-	I-GENE
+-	I-GENE
+gp96	I-GENE
+complexes	I-GENE
+and	O
+the	O
+plasticity	O
+of	O
+the	O
+peptide	O
+-	O
+binding	O
+pocket	O
+support	O
+the	O
+proposed	O
+relay	O
+of	O
+diverse	O
+peptides	O
+to	O
+MHC	B-GENE
+and	O
+/	O
+or	O
+other	O
+molecules	O
+via	O
+molecular	O
+recognition	O
+.	O
+
+High	O
+-	O
+affinity	O
+binding	O
+of	O
+NF	B-GENE
+-	I-GENE
+1	I-GENE
+to	O
+PSE	B-GENE
+-	I-GENE
+B	I-GENE
+,	O
+but	O
+not	O
+to	O
+PSE	B-GENE
+-	I-GENE
+A	I-GENE
+,	O
+was	O
+confirmed	O
+by	O
+competition	O
+of	O
+DNA	O
+-	O
+protein	O
+interactions	O
+by	O
+using	O
+NF	B-GENE
+-	I-GENE
+1	I-GENE
+DNA	O
+elements	O
+and	O
+antibodies	O
+.	O
+
+Coexpression	O
+of	O
+the	O
+p120	B-GENE
+(	O
+ctn	B-GENE
+)	O
+protein	O
+with	O
+an	O
+N	O
+-	O
+terminal	O
+deletion	O
+,	O
+which	O
+eliminates	O
+some	O
+potential	O
+tyrosine	O
+phosphorylation	O
+sites	O
+,	O
+or	O
+the	O
+protein	O
+with	O
+a	O
+single	O
+amino	O
+acid	O
+substitution	O
+(	O
+tyrosine	O
+at	O
+217	O
+to	O
+phenylalanine	O
+)	O
+resulted	O
+in	O
+an	O
+increase	O
+in	O
+the	O
+aggregation	O
+of	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+-	O
+transformed	O
+EL	O
+and	O
+EalphaCL	O
+cells	O
+.	O
+
+We	O
+show	O
+that	O
+p73	B-GENE
+can	O
+transcriptionally	O
+inhibit	O
+a	O
+number	O
+of	O
+cellular	O
+and	O
+viral	O
+promoters	O
+.	O
+
+RESULTS	O
+:	O
+Of	O
+the	O
+24	O
+patients	O
+,	O
+6	O
+had	O
+Grade	O
+1	O
+pneumonitis	O
+,	O
+and	O
+13	O
+had	O
+Grade	O
+2	O
+pneumonitis	O
+.	O
+
+In	O
+contrast	O
+,	O
+we	O
+did	O
+not	O
+detect	O
+a	O
+significant	O
+correlation	O
+between	O
+plasma	B-GENE
+TNFalpha	I-GENE
+and	O
+radiation	O
+pneumonitis	O
+.	O
+
+METHODS	O
+:	O
+Sixteen	O
+pigs	O
+were	O
+assigned	O
+randomly	O
+to	O
+control	O
+and	O
+shock	O
+groups	O
+.	O
+
+Identification	O
+of	O
+pulmonary	O
+vein	O
+stenosis	O
+after	O
+radiofrequency	O
+ablation	O
+for	O
+atrial	O
+fibrillation	O
+using	O
+MRI	O
+.	O
+
+Tumor	O
+cell	O
+lines	O
+transduced	O
+at	O
+an	O
+MOI	O
+of	O
+8	O
+for	O
+3	O
+days	O
+led	O
+to	O
+>	O
+90	O
+%	O
+gene	O
+transfer	O
+efficiency	O
+.	O
+
+Treatment	O
+includes	O
+both	O
+medical	O
+and	O
+surgical	O
+options	O
+,	O
+with	O
+medical	O
+therapy	O
+further	O
+subclassified	O
+into	O
+pharmacologic	O
+and	O
+pneumatic	O
+dilation	O
+.	O
+
+Finally	O
+,	O
+we	O
+compared	O
+the	O
+differential	O
+screening	O
+techniques	O
+in	O
+terms	O
+of	O
+sensitivity	O
+,	O
+efficiency	O
+and	O
+occurrence	O
+of	O
+false	O
+positives	O
+.	O
+
+Serial	O
+US	O
+images	O
+were	O
+obtained	O
+before	O
+and	O
+20	O
+,	O
+30	O
+,	O
+40	O
+,	O
+50	O
+,	O
+60	O
+,	O
+90	O
+,	O
+120	O
+,	O
+150	O
+,	O
+180	O
+,	O
+240	O
+,	O
+and	O
+300	O
+s	O
+after	O
+intravenous	O
+injection	O
+of	O
+2	O
+g	O
+of	O
+contrast	O
+agent	O
+using	O
+conventional	O
+and	O
+harmonic	O
+PD	O
+US	O
+.	O
+
+To	O
+investigate	O
+the	O
+effects	O
+of	O
+exogenous	O
+hyaluronic	O
+acid	O
+,	O
+the	O
+development	O
+of	O
+port	O
+-	O
+site	O
+metastasis	O
+was	O
+examined	O
+using	O
+mouse	O
+adenocarcinoma	O
+cell	O
+-	O
+line	O
+colon	O
+26	O
+cells	O
+.	O
+
+Cytomegalovirus	O
+,	O
+Chlamydia	O
+pneumoniae	O
+,	O
+and	O
+Helicobacter	O
+pylori	O
+IgG	B-GENE
+antibodies	I-GENE
+and	O
+restenosis	O
+after	O
+stent	O
+implantation	O
+:	O
+an	O
+angiographic	O
+and	O
+intravascular	O
+ultrasound	O
+study	O
+.	O
+
+Responses	O
+of	O
+single	O
+-	O
+unit	O
+carotid	O
+body	O
+chemoreceptors	O
+in	O
+adult	O
+rats	O
+.	O
+
+Architecture	O
+and	O
+anatomy	O
+of	O
+the	O
+genomic	O
+locus	O
+encoding	O
+the	O
+human	O
+leukemia	O
+-	O
+associated	O
+transcription	O
+factor	O
+RUNX1	B-GENE
+/	O
+AML1	B-GENE
+.	O
+
+Therefore	O
+,	O
+we	O
+suggested	O
+that	O
+both	O
+proteins	O
+might	O
+belong	O
+to	O
+the	O
+PLTP	B-GENE
+family	I-GENE
+.	O
+
+In	O
+this	O
+paper	O
+the	O
+tyrosine	O
+dephosphorylating	O
+enzymes	O
+,	O
+the	O
+protein	B-GENE
+-	I-GENE
+tyrosine	I-GENE
+phosphatases	I-GENE
+(	O
+PTPs	B-GENE
+)	O
+,	O
+are	O
+studied	O
+which	O
+can	O
+be	O
+grouped	O
+into	O
+two	O
+subfamilies	O
+,	O
+the	O
+soluble	B-GENE
+PTPs	I-GENE
+and	O
+the	O
+receptor	B-GENE
+PTPs	I-GENE
+(	O
+RPTPs	B-GENE
+)	O
+.	O
+
+The	O
+Ig	B-GENE
+-	O
+related	O
+,	O
+typical	O
+metazoan	O
+,	O
+module	O
+is	O
+classified	O
+to	O
+the	O
+disulphide	O
+lacking	O
+Ig	B-GENE
+members	I-GENE
+and	O
+represents	O
+the	O
+phylogenetic	O
+earliest	O
+member	O
+of	O
+this	O
+group	O
+.	O
+
+The	O
+Sox	B-GENE
+gene	I-GENE
+family	I-GENE
+(	O
+Sry	B-GENE
+like	I-GENE
+HMG	I-GENE
+box	I-GENE
+gene	I-GENE
+)	O
+is	O
+characterised	O
+by	O
+a	O
+conserved	O
+DNA	O
+sequence	O
+encoding	O
+a	O
+domain	O
+of	O
+approximately	O
+80	O
+amino	O
+acids	O
+which	O
+is	O
+responsible	O
+for	O
+sequence	O
+specific	O
+DNA	O
+binding	O
+.	O
+
+While	O
+these	O
+results	O
+are	O
+consistent	O
+with	O
+previously	O
+reported	O
+effects	O
+of	O
+the	O
+C	O
+-	O
+terminal	O
+domain	O
+on	O
+nucleotide	O
+binding	O
+,	O
+they	O
+also	O
+demonstrate	O
+that	O
+interactions	O
+with	O
+the	O
+N	O
+-	O
+terminal	O
+domains	O
+are	O
+necessary	O
+to	O
+inhibit	O
+proton	O
+transport	O
+.	O
+
+Respiratory	O
+parameters	O
+suggested	O
+that	O
+M6G	O
+produced	O
+less	O
+respiratory	O
+depression	O
+than	O
+morphine	O
+.	O
+
+This	O
+supports	O
+previous	O
+arguments	O
+for	O
+the	O
+improbability	O
+of	O
+biological	O
+effects	O
+at	O
+UHF	O
+frequencies	O
+unless	O
+a	O
+mechanism	O
+can	O
+be	O
+found	O
+for	O
+accumulating	O
+energy	O
+over	O
+time	O
+and	O
+space	O
+and	O
+focussing	O
+it	O
+.	O
+
+To	O
+assess	O
+the	O
+maximum	O
+oxygen	O
+uptake	O
+(	O
+V	O
+'	O
+O2	O
+max	O
+)	O
+of	O
+Hong	O
+Kong	O
+Chinese	O
+children	O
+and	O
+to	O
+explore	O
+its	O
+association	O
+with	O
+respiratory	O
+illnesses	O
+,	O
+we	O
+conducted	O
+the	O
+Multistage	O
+Fitness	O
+Test	O
+(	O
+MFT	O
+)	O
+,	O
+a	O
+20	O
+-	O
+m	O
+shuttle	O
+run	O
+test	O
+,	O
+in	O
+1	O
+,	O
+427	O
+schoolchildren	O
+aged	O
+between	O
+8	O
+-	O
+12	O
+years	O
+.	O
+
+By	O
+analyzing	O
+5	O
+'	O
+-	O
+deletion	O
+insulin	B-GENE
+promoter	I-GENE
+-	I-GENE
+reporter	I-GENE
+constructs	I-GENE
+in	O
+transient	O
+transfections	O
+of	O
+clonal	O
+INS	B-GENE
+-	I-GENE
+1	I-GENE
+beta	I-GENE
+-	O
+cells	O
+,	O
+we	O
+located	O
+activating	O
+Hh	B-GENE
+-	O
+responsive	O
+regions	O
+within	O
+the	O
+rat	B-GENE
+insulin	I-GENE
+I	I-GENE
+promoter	I-GENE
+that	O
+include	O
+the	O
+glucose	O
+-	O
+response	O
+elements	O
+Far	O
+(	O
+E2	O
+)	O
+and	O
+Flat	O
+(	O
+A2	O
+/	O
+A3	O
+)	O
+.	O
+
+The	O
+androgen	B-GENE
+receptor	I-GENE
+(	O
+AR	B-GENE
+)	O
+amino	O
+-	O
+terminus	O
+imposes	O
+androgen	O
+-	O
+specific	O
+regulation	O
+of	O
+AR	B-GENE
+gene	I-GENE
+expression	O
+via	O
+an	O
+exonic	O
+enhancer	O
+.	O
+
+A	O
+major	O
+mechanism	O
+by	O
+which	O
+estrogens	O
+prevent	O
+osteoporosis	O
+seems	O
+to	O
+be	O
+repression	O
+of	O
+transcription	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappa	I-GENE
+B	I-GENE
+target	I-GENE
+genes	I-GENE
+,	O
+such	O
+as	O
+the	O
+osteoclast	O
+-	O
+activating	O
+cytokines	O
+interleukin	B-GENE
+-	I-GENE
+6	I-GENE
+and	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+.	O
+
+To	O
+identify	O
+the	O
+important	O
+cis	O
+-	O
+DNA	O
+regulatory	O
+element	O
+(	O
+s	O
+)	O
+involved	O
+in	O
+the	O
+tissue	O
+-	O
+,	O
+region	O
+-	O
+,	O
+and	O
+cell	O
+-	O
+specific	O
+expression	O
+of	O
+the	O
+mE	B-GENE
+-	I-GENE
+RABP	I-GENE
+gene	I-GENE
+,	O
+the	O
+5	O
+-	O
+kb	O
+DNA	O
+fragment	O
+was	O
+sequenced	O
+.	O
+
+In	O
+the	O
+mouse	O
+,	O
+both	O
+genes	O
+reside	O
+in	O
+the	O
+syntenic	O
+region	O
+8E1	O
+on	O
+chromosome	O
+8	O
+.	O
+
+Analysis	O
+of	O
+the	O
+genome	O
+sequence	O
+revealed	O
+26	O
+,	O
+588	O
+protein	O
+-	O
+encoding	O
+transcripts	O
+for	O
+which	O
+there	O
+was	O
+strong	O
+corroborating	O
+evidence	O
+and	O
+an	O
+additional	O
+approximately	O
+12	O
+,	O
+000	O
+computationally	O
+derived	O
+genes	O
+with	O
+mouse	O
+matches	O
+or	O
+other	O
+weak	O
+supporting	O
+evidence	O
+.	O
+
+The	O
+corresponding	O
+genotype	O
+was	O
+determined	O
+with	O
+a	O
+restriction	O
+enzyme	O
+-	O
+based	O
+assay	O
+.	O
+
+By	O
+Caveman	O
+.	O
+
+Multistage	O
+models	O
+and	O
+the	O
+A	O
+-	O
+bomb	O
+survivor	O
+data	O
+:	O
+implications	O
+for	O
+carcinogenic	O
+mechanisms	O
+?	O
+
+The	O
+revitalization	O
+of	O
+surgery	O
+for	O
+Parkinson	O
+'	O
+s	O
+disease	O
+(	O
+PD	O
+)	O
+has	O
+fueled	O
+discussion	O
+about	O
+the	O
+best	O
+methodology	O
+to	O
+define	O
+the	O
+target	O
+.	O
+
+Corneal	O
+scrapping	O
+and	O
+deep	O
+stromal	O
+biopsy	O
+were	O
+obtained	O
+and	O
+stained	O
+for	O
+microscopic	O
+evaluation	O
+with	O
+periodic	O
+acid	O
+-	O
+Schiff	O
+,	O
+Giemsa	O
+,	O
+and	O
+Gomori	O
+'	O
+s	O
+methenamine	O
+silver	O
+stains	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+BACM	O
+has	O
+antiplaque	O
+and	O
+stronger	O
+antidegradation	O
+effects	O
+than	O
+GLCM	O
+.	O
+
+Multidrug	O
+resistance	O
+in	O
+Saccharomyces	O
+cerevisiae	O
+mainly	O
+results	O
+from	O
+the	O
+overexpression	O
+of	O
+genes	O
+coding	O
+for	O
+the	O
+membrane	O
+efflux	O
+pumps	O
+,	O
+the	O
+major	O
+facilitators	O
+and	O
+the	O
+ABC	B-GENE
+binding	I-GENE
+cassette	I-GENE
+transporters	I-GENE
+,	O
+under	O
+the	O
+control	O
+of	O
+key	O
+transcription	O
+regulators	O
+encoded	O
+by	O
+the	O
+PDR1	B-GENE
+and	O
+PDR3	B-GENE
+genes	I-GENE
+.	O
+
+Susceptibility	O
+to	O
+ischemia	O
+-	O
+induced	O
+arrhythmias	O
+was	O
+lower	O
+in	O
+1	O
+-	O
+week	O
+diabetics	O
+:	O
+only	O
+42	O
+%	O
+of	O
+diabetic	O
+hearts	O
+exhibited	O
+ventricular	O
+tachycardia	O
+(	O
+VT	O
+)	O
+and	O
+16	O
+%	O
+had	O
+short	O
+episodes	O
+of	O
+ventricular	O
+fibrillation	O
+(	O
+VF	O
+)	O
+as	O
+compared	O
+to	O
+VT	O
+100	O
+%	O
+and	O
+VF	O
+70	O
+%	O
+(	O
+including	O
+sustained	O
+VF	O
+36	O
+%	O
+)	O
+in	O
+the	O
+non	O
+-	O
+diabetics	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+A	O
+picture	O
+is	O
+emerging	O
+showing	O
+a	O
+gradient	O
+of	O
+function	O
+among	O
+p53	B-GENE
+,	O
+p73	B-GENE
+,	O
+p63	B-GENE
+ranging	O
+from	O
+tumor	O
+suppression	O
+to	O
+development	O
+.	O
+
+This	O
+could	O
+lead	O
+to	O
+subsequent	O
+outbreaks	O
+if	O
+Babesia	O
+carrier	O
+animals	O
+were	O
+to	O
+be	O
+introduced	O
+into	O
+the	O
+herd	O
+.	O
+
+Contagious	O
+bovine	O
+pleuropneumonia	O
+is	O
+a	O
+major	O
+threat	O
+for	O
+cattle	O
+in	O
+Africa	O
+.	O
+
+Baseline	O
+BMD	O
+values	O
+were	O
+significantly	O
+lower	O
+in	O
+the	O
+oligo	O
+-	O
+amenorrheic	O
+group	O
+than	O
+in	O
+the	O
+two	O
+others	O
+at	O
+the	O
+level	O
+of	O
+lumbar	O
+spine	O
+(	O
+anteroposterior	O
+view	O
+:	O
+0	O
+.	O
+941	O
++	O
+/	O
+-	O
+0	O
+.	O
+039	O
+in	O
+oligo	O
+-	O
+amenorrheic	O
+vs	O
+1	O
+.	O
+077	O
++	O
+/	O
+-	O
+0	O
+.	O
+029	O
+or	O
+1	O
+.	O
+051	O
++	O
+/	O
+-	O
+0	O
+.	O
+017	O
+g	O
+x	O
+cm	O
+(	O
+-	O
+2	O
+)	O
+,	O
+P	O
+<	O
+0	O
+.	O
+005	O
+,	O
+in	O
+the	O
+eumenorrheic	O
+and	O
+contraceptive	O
+user	O
+groups	O
+,	O
+respectively	O
+)	O
+but	O
+not	O
+in	O
+weight	O
+-	O
+bearing	O
+bone	O
+such	O
+as	O
+proximal	O
+and	O
+midshaft	O
+femur	O
+.	O
+
+The	O
+distribution	O
+of	O
+red	O
+rice	O
+cultivation	O
+in	O
+Sri	O
+Lanka	O
+is	O
+coincident	O
+with	O
+the	O
+HIDD	O
+villages	O
+.	O
+
+The	O
+increase	O
+in	O
+number	O
+of	O
+terminal	O
+hairs	O
+,	O
+which	O
+are	O
+defined	O
+as	O
+hairs	O
+more	O
+than	O
+60	O
+microm	O
+in	O
+diameter	O
+,	O
+in	O
+the	O
+designated	O
+area	O
+(	O
+0	O
+.	O
+5	O
+cm	O
+square	O
+=	O
+0	O
+.	O
+25	O
+cm2	O
+area	O
+)	O
+of	O
+the	O
+procyanidin	O
+B	O
+-	O
+2	O
+group	O
+subjects	O
+after	O
+the	O
+6	O
+-	O
+month	O
+trial	O
+was	O
+significantly	O
+greater	O
+than	O
+that	O
+of	O
+the	O
+placebo	O
+control	O
+group	O
+subjects	O
+(	O
+procyanidin	O
+B	O
+-	O
+2	O
+,	O
+1	O
+.	O
+99	O
++	O
+/	O
+-	O
+2	O
+.	O
+58	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+/	O
+0	O
+.	O
+25	O
+cm2	O
+;	O
+placebo	O
+,	O
+-	O
+0	O
+.	O
+82	O
++	O
+/	O
+-	O
+3	O
+.	O
+40	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+/	O
+0	O
+.	O
+25	O
+cm2	O
+;	O
+P	O
+<	O
+0	O
+.	O
+02	O
+,	O
+two	O
+-	O
+sample	O
+t	O
+test	O
+)	O
+.	O
+
+Ectopic	O
+expression	O
+of	O
+the	O
+dominant	B-GENE
+mutant	I-GENE
+Lg3	I-GENE
+allele	I-GENE
+is	O
+believed	O
+to	O
+cause	O
+the	O
+phenotype	O
+.	O
+
+High	O
+plasma	B-GENE
+AVP	I-GENE
+levels	O
+observed	O
+in	O
+the	O
+two	O
+cases	O
+suggest	O
+that	O
+SSRIs	O
+stimulate	O
+AVP	B-GENE
+secretion	O
+,	O
+thereby	O
+causing	O
+SIADH	O
+.	O
+
+Thus	O
+,	O
+in	O
+T47D	O
+breast	O
+carcinoma	O
+cells	O
+,	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+acts	O
+in	O
+synergy	O
+with	O
+EGF	B-GENE
+receptor	I-GENE
+autocrine	O
+activity	O
+to	O
+signal	O
+through	O
+the	O
+MAPK	B-GENE
+/	O
+PI3K	B-GENE
+pathways	O
+.	O
+
+Human	B-GENE
+homologue	I-GENE
+of	I-GENE
+yeast	I-GENE
+Rad23	I-GENE
+protein	I-GENE
+A	I-GENE
+interacts	O
+with	O
+p300	B-GENE
+/	O
+cyclic	B-GENE
+AMP	I-GENE
+-	I-GENE
+responsive	I-GENE
+element	I-GENE
+binding	I-GENE
+(	I-GENE
+CREB	I-GENE
+)	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+to	O
+down	O
+-	O
+regulate	O
+transcriptional	O
+activity	O
+of	O
+p53	B-GENE
+.	O
+
+Most	O
+patients	O
+harboring	O
+metronidazole	O
+-	O
+and	O
+clarithromycin	O
+-	O
+resistant	O
+strains	O
+were	O
+eradicated	O
+at	O
+an	O
+equal	O
+rate	O
+by	O
+each	O
+of	O
+the	O
+three	O
+regimens	O
+.	O
+
+Binding	O
+of	O
+cell	O
+type	O
+-	O
+specific	O
+nuclear	O
+proteins	O
+to	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+maize	B-GENE
+C4	I-GENE
+phosphoenolpyruvate	I-GENE
+carboxylase	I-GENE
+gene	I-GENE
+confers	O
+its	O
+differential	O
+transcription	O
+in	O
+mesophyll	O
+cells	O
+.	O
+
+RESULTS	O
+:	O
+During	O
+the	O
+stabilization	O
+period	O
+,	O
+PaCO2	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+was	O
+33	O
++	O
+/	O
+-	O
+5	O
+mm	O
+Hg	O
+,	O
+and	O
+arrhythmias	O
+were	O
+not	O
+detected	O
+.	O
+
+BACKGROUND	O
+:	O
+Previous	O
+studies	O
+have	O
+indicated	O
+that	O
+the	O
+60	O
+-	O
+,	O
+30	O
+-	O
+,	O
+28	O
+-	O
+and	O
+12	O
+-	O
+item	O
+versions	O
+of	O
+the	O
+General	O
+Health	O
+Questionnaire	O
+(	O
+GHQ	O
+)	O
+are	O
+liable	O
+to	O
+retest	O
+effects	O
+,	O
+especially	O
+when	O
+administered	O
+multiple	O
+times	O
+with	O
+short	O
+intervals	O
+.	O
+
+Acute	O
+effects	O
+of	O
+LI	O
+160	O
+(	O
+extract	O
+of	O
+Hypericum	O
+perforatum	O
+,	O
+St	O
+John	O
+'	O
+s	O
+wort	O
+)	O
+and	O
+two	O
+of	O
+its	O
+constituents	O
+on	O
+neuroendocrine	O
+responses	O
+in	O
+the	O
+rat	O
+.	O
+
+Decreased	O
+serum	B-GENE
+ceruloplasmin	I-GENE
+and	O
+copper	O
+levels	O
+in	O
+cervical	O
+dystonia	O
+.	O
+
+A	O
+microsporidian	O
+,	O
+Nosema	O
+algerae	O
+Vavra	O
+and	O
+undeen	O
+,	O
+was	O
+found	O
+parasitizing	O
+larvae	O
+and	O
+adults	O
+of	O
+a	O
+laboratory	O
+colony	O
+of	O
+Culex	O
+pipiens	O
+L	O
+.	O
+originated	O
+from	O
+Gharbia	O
+Governorate	O
+.	O
+
+Molecular	O
+cloning	O
+and	O
+characterization	O
+of	O
+OsPSK	B-GENE
+,	O
+a	O
+gene	O
+encoding	O
+a	O
+precursor	O
+for	O
+phytosulfokine	B-GENE
+-	I-GENE
+alpha	I-GENE
+,	O
+required	O
+for	O
+rice	O
+cell	O
+proliferation	O
+.	O
+
+Plasma	O
+DHE	O
+concentration	O
+rose	O
+promptly	O
+above	O
+5	O
+ng	O
+/	O
+ml	O
+after	O
+the	O
+application	O
+of	O
+the	O
+PSA	O
+tape	O
+onto	O
+the	O
+damaged	O
+skin	O
+in	O
+hairless	O
+rat	O
+.	O
+
+Implications	O
+in	O
+biomonitoring	O
+of	O
+the	O
+observed	O
+accumulation	O
+patterns	O
+,	O
+especially	O
+in	O
+the	O
+different	O
+tissues	O
+of	O
+Posidonia	O
+oceanica	O
+,	O
+are	O
+discussed	O
+.	O
+
+Thus	O
+,	O
+Xlim	B-GENE
+-	I-GENE
+1	I-GENE
+not	O
+only	O
+contains	O
+a	O
+unique	O
+tyrosine	O
+-	O
+rich	O
+activation	O
+domain	O
+but	O
+also	O
+contains	O
+a	O
+negative	O
+regulatory	O
+domain	O
+in	O
+CT239	O
+-	O
+403	O
+,	O
+suggesting	O
+a	O
+complex	O
+regulatory	O
+mechanism	O
+underlying	O
+the	O
+transcriptional	O
+activity	O
+of	O
+Xlim	B-GENE
+-	I-GENE
+1	I-GENE
+in	O
+the	O
+organizer	O
+.	O
+
+After	O
+allowing	O
+time	O
+for	O
+absorption	O
+,	O
+participants	O
+completed	O
+a	O
+bridge	O
+simulator	O
+task	O
+.	O
+
+Functional	O
+analysis	O
+of	O
+various	O
+PTP	B-GENE
+-	O
+deficient	O
+DT40	O
+B	O
+cell	O
+lines	O
+stably	O
+expressing	O
+wild	O
+-	O
+type	O
+chimeric	O
+Fc	B-GENE
+gamma	I-GENE
+RIIB1	I-GENE
+-	I-GENE
+PECAM	I-GENE
+-	I-GENE
+1	I-GENE
+receptor	I-GENE
+indicated	O
+that	O
+cytoplasmic	B-GENE
+Src	I-GENE
+homology	I-GENE
+2	I-GENE
+-	I-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+phosphatases	I-GENE
+,	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+and	O
+SHP	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+were	O
+both	O
+necessary	O
+and	O
+sufficient	O
+to	O
+deliver	O
+inhibitory	O
+negative	O
+regulation	O
+upon	O
+coligation	O
+of	O
+BCR	B-GENE
+complex	I-GENE
+with	O
+inhibitory	O
+receptor	O
+.	O
+
+Substitutions	O
+in	O
+the	O
+YFV	B-GENE
+Ag	B-GENE
+-	I-GENE
+binding	I-GENE
+region	I-GENE
+(	O
+ABR	B-GENE
+)	O
+occur	O
+at	O
+four	O
+of	O
+the	O
+eight	O
+highly	O
+conserved	O
+residues	O
+that	O
+are	O
+essential	O
+for	O
+binding	O
+of	O
+peptide	O
+-	O
+Ag	O
+in	O
+the	O
+class	O
+Ia	O
+molecules	O
+.	O
+
+Similarly	O
+,	O
+curcumin	O
+(	O
+diferuloylmethane	O
+)	O
+,	O
+an	O
+anti	O
+-	O
+inflammatory	O
+agent	O
+,	O
+suppressed	O
+OSM	B-GENE
+-	O
+stimulated	O
+STAT1	B-GENE
+phosphorylation	O
+,	O
+DNA	O
+-	O
+binding	O
+activity	O
+of	O
+STAT1	B-GENE
+,	O
+and	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+activation	O
+without	O
+affecting	O
+JAK1	B-GENE
+,	O
+JAK2	B-GENE
+,	O
+JAK3	B-GENE
+,	O
+ERK1	B-GENE
+/	I-GENE
+2	I-GENE
+,	O
+and	O
+p38	B-GENE
+phosphorylation	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+failure	O
+of	O
+the	O
+QKTT	O
+motif	O
+and	O
+TGN46	O
+cytoplasmic	O
+tail	O
+to	O
+induce	O
+steady	O
+-	O
+state	O
+ER	O
+localization	O
+of	O
+vesicular	B-GENE
+stomatitis	I-GENE
+virus	I-GENE
+glycoprotein	I-GENE
+(	O
+VSVG	B-GENE
+)	O
+chimeras	O
+in	O
+HeLa	O
+and	O
+NRK	O
+cells	O
+indicates	O
+that	O
+significant	O
+differences	O
+in	O
+early	O
+secretory	O
+trafficking	O
+also	O
+exist	O
+.	O
+
+A	O
+cDNA	O
+clone	O
+encoding	O
+C2H2	B-GENE
+-	I-GENE
+type	I-GENE
+zinc	I-GENE
+finger	I-GENE
+protein	I-GENE
+,	O
+SCOF	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+was	O
+isolated	O
+from	O
+soybean	O
+.	O
+
+Consistent	O
+with	O
+the	O
+specificity	O
+observed	O
+for	O
+the	O
+interaction	O
+of	O
+DmCKIIalpha	B-GENE
+with	O
+these	O
+bHLH	B-GENE
+proteins	I-GENE
+,	O
+sequence	O
+alignment	O
+suggests	O
+that	O
+only	O
+m5	B-GENE
+,	O
+m7	B-GENE
+,	O
+and	O
+m8	B-GENE
+contain	O
+a	O
+consensus	O
+site	O
+for	O
+phosphorylation	O
+by	O
+CKII	B-GENE
+within	O
+a	O
+subdomain	O
+unique	O
+to	O
+these	O
+three	O
+proteins	O
+.	O
+
+Apart	O
+from	O
+antimicrobial	O
+properties	O
+,	O
+recent	O
+data	O
+indicate	O
+that	O
+PMN	O
+also	O
+exert	O
+anti	O
+-	O
+inflammatory	O
+effects	O
+by	O
+stimulation	O
+and	O
+release	O
+of	O
+cytokine	O
+antagonists	O
+such	O
+as	O
+interleukin	B-GENE
+-	I-GENE
+1	I-GENE
+receptor	I-GENE
+antagonist	I-GENE
+(	O
+IL	B-GENE
+-	I-GENE
+1ra	I-GENE
+)	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+investigation	O
+was	O
+to	O
+study	O
+the	O
+morphological	O
+characteristics	O
+of	O
+the	O
+fibrous	O
+tissue	O
+capsule	O
+resulting	O
+from	O
+the	O
+implantation	O
+of	O
+aluminum	O
+calcium	O
+phosphate	O
+(	O
+ALCAP	O
+)	O
+and	O
+hydroxyapetite	O
+(	O
+HA	O
+)	O
+bioceramics	O
+.	O
+
+Sevelamer	O
+hydrochloride	O
+(	O
+Renagel	O
+)	O
+is	O
+a	O
+nonabsorbed	O
+phosphate	O
+-	O
+binding	O
+polymer	O
+marketed	O
+for	O
+the	O
+treatment	O
+of	O
+hyperphosphatemia	O
+in	O
+adult	O
+patients	O
+receiving	O
+hemodialysis	O
+.	O
+
+The	O
+pharmacokinetic	O
+profiles	O
+of	O
+digoxin	O
+and	O
+warfarin	O
+were	O
+not	O
+altered	O
+by	O
+the	O
+simultaneous	O
+and	O
+continued	O
+administration	O
+of	O
+sevelamer	O
+.	O
+
+Before	O
+PO3	O
+administration	O
+,	O
+more	O
+than	O
+half	O
+(	O
+57	O
+.	O
+4	O
+%	O
+)	O
+of	O
+the	O
+patients	O
+received	O
+only	O
+1	O
+or	O
+2	O
+antituberculous	O
+drugs	O
+(	O
+ethambutole	O
+and	O
+ethionamide	O
+or	O
+ethambutole	O
+and	O
+oprofloxacin	O
+)	O
+.	O
+
+Can	O
+survival	O
+be	O
+prolonged	O
+for	O
+patients	O
+with	O
+hormone	O
+-	O
+resistant	O
+prostate	O
+cancer	O
+?	O
+
+Patients	O
+were	O
+divided	O
+into	O
+two	O
+group	O
+;	O
+Control	O
+group	O
+A	O
+in	O
+which	O
+a	O
+hot	O
+-	O
+water	O
+circulating	O
+system	O
+was	O
+used	O
+and	O
+group	O
+B	O
+in	O
+which	O
+a	O
+transtracheal	O
+heating	O
+and	O
+humidification	O
+system	O
+by	O
+ANAMED	O
+HUMITUBE	O
+was	O
+used	O
+,	O
+during	O
+gastric	O
+cancer	O
+operation	O
+.	O
+
+The	O
+present	O
+data	O
+also	O
+demonstrate	O
+that	O
+ectopic	O
+expression	O
+of	O
+blr1	B-GENE
+increased	O
+JNK	B-GENE
+/	O
+SAPK	B-GENE
+activity	O
+,	O
+but	O
+JNK	B-GENE
+/	O
+SAPK	B-GENE
+activation	O
+was	O
+not	O
+needed	O
+for	O
+accelerated	O
+RA	O
+-	O
+induced	O
+differentiation	O
+and	O
+growth	O
+arrest	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+parameters	O
+SF2	O
+and	O
+plating	O
+efficiency	O
+were	O
+stable	O
+throughout	O
+the	O
+4	O
+-	O
+year	O
+test	O
+period	O
+.	O
+
+Also	O
+,	O
+small	O
+,	O
+sense	O
+and	O
+antisense	O
+approximately	O
+22	O
+nt	O
+RNAs	O
+,	O
+derived	O
+from	O
+the	O
+satRNA	O
+,	O
+were	O
+associated	O
+with	O
+the	O
+replicating	O
+satellite	O
+.	O
+
+VE	O
+-	O
+DEF	O
+animals	O
+had	O
+significantly	O
+higher	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+levels	O
+of	O
+myocardial	O
+lipid	O
+peroxidation	O
+and	O
+lower	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+protein	O
+thiols	O
+following	O
+I	O
+-	O
+R	O
+compared	O
+to	O
+the	O
+CON	O
+animals	O
+.	O
+
+Grippers	O
+with	O
+integrated	O
+piezoresistive	O
+force	O
+sensors	O
+and	O
+with	O
+attached	O
+strain	O
+gauges	O
+have	O
+been	O
+reported	O
+.	O
+
+The	O
+child	O
+left	O
+behind	O
+.	O
+
+Transition	O
+between	O
+P	O
+-	O
+and	O
+H	O
+-	O
+BPPV	O
+was	O
+found	O
+in	O
+6	O
+cases	O
+.	O
+
+The	O
+contrasting	O
+effects	O
+of	O
+dopaminergic	O
+stimulation	O
+on	O
+the	O
+motor	O
+performance	O
+and	O
+on	O
+some	O
+aspects	O
+of	O
+cognitive	O
+processing	O
+suggest	O
+the	O
+existence	O
+of	O
+complex	O
+interactions	O
+within	O
+pre	O
+-	O
+and	O
+postsynaptic	O
+brain	B-GENE
+dopamine	I-GENE
+receptors	I-GENE
+,	O
+and	O
+an	O
+intervention	O
+of	O
+segregated	O
+basal	O
+ganglia	O
+-	O
+prefrontal	O
+cortex	O
+loops	O
+in	O
+motor	O
+and	O
+cognitive	O
+behaviour	O
+.	O
+
+HexA71	B-GENE
+negatively	O
+affects	O
+RpoS	B-GENE
+,	O
+as	O
+the	O
+levels	O
+of	O
+this	O
+alternative	O
+sigma	B-GENE
+factor	I-GENE
+are	O
+higher	O
+in	O
+the	O
+HexA	B-GENE
+-	I-GENE
+mutant	I-GENE
+than	O
+in	O
+the	O
+HexA	B-GENE
++	I-GENE
+strain	O
+.	O
+
+Multiple	O
+copies	O
+of	O
+rsmB	B-GENE
++	I-GENE
+DNA	I-GENE
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+stimulate	O
+exoenzyme	O
+production	O
+by	O
+relieving	O
+the	O
+negative	O
+effects	O
+of	O
+a	O
+chromosomal	O
+copy	O
+of	O
+hexA	B-GENE
++	I-GENE
+.	O
+
+0	O
+%	O
+)	O
+and	O
+IL	B-GENE
+-	I-GENE
+12	I-GENE
+(	O
+42	O
+.	O
+6	O
+%	O
+vs	O
+.	O
+
+Systematic	O
+review	O
+of	O
+diagnostic	O
+tests	O
+for	O
+vaginal	O
+trichomoniasis	O
+.	O
+
+CHAP	O
+and	O
+the	O
+Department	O
+of	O
+Veterans	O
+Affairs	O
+.	O
+
+More	O
+importantly	O
+,	O
+this	O
+fusion	O
+converted	O
+a	O
+less	O
+effective	O
+vaccine	O
+into	O
+one	O
+with	O
+significant	O
+potency	O
+against	O
+established	O
+E7	B-GENE
+-	O
+expressing	O
+metastatic	O
+tumors	O
+.	O
+
+We	O
+compared	O
+previously	O
+the	O
+methylation	O
+status	O
+between	O
+normal	O
+liver	O
+and	O
+liver	O
+tumors	O
+in	O
+SV40	B-GENE
+T	I-GENE
+/	I-GENE
+t	I-GENE
+antigen	I-GENE
+transgenic	O
+mice	O
+(	O
+MT	O
+-	O
+D2	O
+mice	O
+)	O
+using	O
+Restriction	O
+Landmark	O
+Genomic	O
+Scanning	O
+for	O
+Methylation	O
+(	O
+RLGS	O
+-	O
+M	O
+)	O
+and	O
+identified	O
+several	O
+loci	O
+/	O
+spots	O
+that	O
+appeared	O
+to	O
+be	O
+methylated	O
+frequently	O
+in	O
+liver	O
+tumors	O
+.	O
+
+The	O
+Genescan	O
+program	O
+predicted	O
+an	O
+open	O
+reading	O
+frame	O
+of	O
+a	O
+novel	O
+,	O
+intron	O
+-	O
+less	O
+gene	O
+adjacent	O
+to	O
+the	O
+B236	O
+spot	O
+that	O
+encodes	O
+a	O
+putative	O
+493	O
+-	O
+amino	O
+acid	O
+protein	O
+containing	O
+the	O
+SNAG	O
+repressor	O
+motif	O
+in	O
+the	O
+NH2	O
+-	O
+terminal	O
+region	O
+and	O
+five	O
+C2H2	O
+-	O
+type	O
+zinc	O
+finger	O
+motifs	O
+in	O
+the	O
+COOH	O
+-	O
+terminal	O
+half	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+revealed	O
+that	O
+mlt	B-GENE
+1	I-GENE
+is	O
+normally	O
+expressed	O
+in	O
+brain	O
+,	O
+spleen	O
+,	O
+stom	O
+ach	O
+,	O
+and	O
+liver	O
+.	O
+
+Treatment	O
+of	O
+N18TG	O
+-	O
+2	O
+cells	O
+with	O
+a	O
+demethylating	O
+agent	O
+,	O
+5	O
+-	O
+aza	O
+-	O
+deoxycytidine	O
+,	O
+resulted	O
+in	O
+an	O
+expression	O
+of	O
+mlt	B-GENE
+1	I-GENE
+,	O
+indicating	O
+that	O
+the	O
+repression	O
+of	O
+mlt	B-GENE
+1	I-GENE
+is	O
+attributable	O
+to	O
+methylation	O
+Thus	O
+,	O
+mlt	B-GENE
+1	I-GENE
+is	O
+a	O
+novel	O
+target	O
+gene	O
+that	O
+is	O
+silenced	O
+by	O
+methylation	O
+during	O
+liver	O
+tumorigenesis	O
+initiated	O
+by	O
+SV40	B-GENE
+T	I-GENE
+antigen	I-GENE
+.	O
+
+These	O
+results	O
+suggested	O
+a	O
+critical	O
+role	O
+for	O
+tyrosine	O
+residue	O
+1229	O
+in	O
+the	O
+regulation	O
+of	O
+L1	B-GENE
+endocytosis	O
+.	O
+
+Folate	O
+metabolism	O
+in	O
+the	O
+human	O
+malaria	O
+parasite	O
+Plasmodium	O
+falciparum	O
+is	O
+an	O
+essential	O
+activity	O
+for	O
+cell	O
+growth	O
+and	O
+replication	O
+,	O
+and	O
+the	O
+target	O
+of	O
+an	O
+important	O
+class	O
+of	O
+therapeutic	O
+agents	O
+in	O
+widespread	O
+use	O
+.	O
+
+The	O
+BFA	O
+System	O
+reads	O
+a	O
+text	O
+file	O
+with	O
+flows	O
+,	O
+measured	O
+with	O
+fluorescent	O
+microsphere	O
+technique	O
+,	O
+and	O
+constructs	O
+the	O
+lung	O
+anatomy	O
+with	O
+volumetric	O
+pixels	O
+showing	O
+the	O
+flows	O
+with	O
+a	O
+color	O
+schema	O
+.	O
+
+Retinoids	O
+participate	O
+in	O
+the	O
+onset	O
+of	O
+differentiation	O
+,	O
+apoptosis	O
+and	O
+the	O
+inhibition	O
+of	O
+growth	O
+in	O
+a	O
+wide	O
+variety	O
+of	O
+normal	O
+and	O
+cancerous	O
+cells	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+evaluation	O
+of	O
+exposure	O
+to	O
+S	O
+.	O
+neurona	O
+by	O
+WB	O
+analysis	O
+of	O
+serum	O
+may	O
+be	O
+misleading	O
+in	O
+young	O
+horses	O
+.	O
+
+Drosophila	B-GENE
+Menin1	I-GENE
+gene	I-GENE
+transcripts	I-GENE
+use	O
+alternative	O
+polyadenylation	O
+sites	O
+resulting	O
+in	O
+4	O
+.	O
+3	O
+and	O
+5	O
+-	O
+kb	O
+messages	O
+.	O
+
+Sequence	O
+analysis	O
+indicates	O
+that	O
+RBP21	B-GENE
+shares	O
+homology	O
+with	O
+other	O
+retinoblastoma	B-GENE
+-	I-GENE
+binding	I-GENE
+proteins	I-GENE
+in	O
+the	O
+pRb	B-GENE
+-	I-GENE
+binding	I-GENE
+motif	I-GENE
+LxCxE	O
+at	O
+the	O
+C	O
+-	O
+terminal	O
+region	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+consensus	O
+amino	O
+acid	O
+motif	O
+for	O
+serine	B-GENE
+threonine	I-GENE
+receptor	I-GENE
+kinases	I-GENE
+was	O
+also	O
+present	O
+.	O
+
+We	O
+have	O
+also	O
+isolated	O
+and	O
+analyzed	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+of	O
+the	O
+pea	O
+33RNP	B-GENE
+gene	I-GENE
+.	O
+
+OsBBPI	B-GENE
+was	O
+found	O
+to	O
+be	O
+rapidly	O
+induced	O
+in	O
+rice	O
+seedling	O
+leaf	O
+in	O
+response	O
+to	O
+cut	B-GENE
+,	O
+exogenous	O
+jasmonic	O
+acid	O
+(	O
+JA	O
+)	O
+,	O
+and	O
+two	O
+potent	O
+protein	B-GENE
+phosphatase	I-GENE
+2A	I-GENE
+(	O
+PP2A	B-GENE
+)	O
+inhibitors	O
+,	O
+cantharidin	O
+(	O
+CN	O
+)	O
+and	O
+endothall	O
+(	O
+EN	O
+)	O
+,	O
+in	O
+a	O
+light	O
+/	O
+dark	O
+-	O
+,	O
+time	O
+-	O
+and	O
+dose	O
+-	O
+dependent	O
+manner	O
+;	O
+this	O
+induction	O
+was	O
+completely	O
+inhibited	O
+by	O
+cycloheximide	O
+(	O
+CHX	O
+)	O
+,	O
+indicating	O
+a	O
+requirement	O
+for	O
+de	O
+novo	O
+protein	O
+synthesis	O
+in	O
+its	O
+induction	O
+.	O
+
+The	O
+effects	O
+of	O
+chlordiazepoxide	O
+(	O
+2	O
+.	O
+5	O
+-	O
+15	O
+.	O
+0mg	O
+/	O
+kg	O
+)	O
+,	O
+a	O
+full	O
+benzodiazepine	B-GENE
+receptor	I-GENE
+agonist	O
+,	O
+and	O
+bretazenil	O
+(	O
+5	O
+.	O
+0	O
+-	O
+30	O
+.	O
+0mg	O
+/	O
+kg	O
+)	O
+,	O
+a	O
+partial	O
+benzodiazepine	B-GENE
+receptor	I-GENE
+agonist	O
+,	O
+were	O
+examined	O
+in	O
+the	O
+murine	O
+elevated	O
+plus	O
+-	O
+maze	O
+paradigm	O
+.	O
+
+However	O
+,	O
+plasmids	O
+carrying	O
+the	O
+yeast	B-GENE
+TyrRS	I-GENE
+gene	I-GENE
+could	O
+not	O
+be	O
+stably	O
+maintained	O
+in	O
+E	O
+.	O
+coli	O
+.	O
+
+In	O
+mammalian	O
+tissue	O
+culture	O
+cells	O
+,	O
+overexpression	O
+of	O
+any	O
+of	O
+the	O
+four	O
+mouse	O
+deltex	O
+homologs	O
+suppressed	O
+the	O
+transcriptional	O
+activity	O
+of	O
+E47	B-GENE
+,	O
+a	O
+basic	B-GENE
+helix	I-GENE
+-	I-GENE
+loop	I-GENE
+-	I-GENE
+helix	I-GENE
+(	I-GENE
+bHLH	I-GENE
+)	I-GENE
+protein	I-GENE
+,	O
+in	O
+a	O
+manner	O
+similar	O
+to	O
+suppression	O
+by	O
+an	O
+activated	O
+form	O
+of	O
+human	B-GENE
+Notch1	I-GENE
+or	O
+human	B-GENE
+DTX1	I-GENE
+.	O
+
+Multiparous	O
+women	O
+presented	O
+higher	O
+BMI	O
+(	O
+P	O
+=	O
+0	O
+.	O
+01	O
+)	O
+and	O
+PBF	O
+(	O
+P	O
+=	O
+0	O
+.	O
+03	O
+)	O
+compared	O
+with	O
+primi	O
+-	O
+and	O
+nulliparous	O
+groups	O
+.	O
+
+The	O
+authors	O
+did	O
+not	O
+detect	O
+any	O
+significant	O
+correlations	O
+between	O
+parameters	O
+of	O
+the	O
+lipids	O
+of	O
+bone	O
+marrow	O
+and	O
+leptin	B-GENE
+levels	O
+in	O
+serum	O
+and	O
+bone	O
+marrow	O
+.	O
+
+The	O
+position	O
+of	O
+the	O
+analyst	O
+as	O
+expert	O
+:	O
+yesterday	O
+and	O
+today	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+the	O
+central	O
+role	O
+of	O
+the	O
+Notch	B-GENE
+-	O
+CBF1	B-GENE
+/	O
+RBP	B-GENE
+-	I-GENE
+Jkappa	I-GENE
+signaling	O
+pathway	O
+in	O
+cell	O
+fate	O
+decisions	O
+renders	O
+it	O
+susceptible	O
+to	O
+pathways	O
+of	O
+viral	O
+replication	O
+and	O
+oncogenic	O
+conversion	O
+.	O
+
+Using	O
+a	O
+novel	O
+method	O
+combining	O
+chromatin	O
+immunoprecipitation	O
+and	O
+genomic	O
+array	O
+hybridization	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+460	B-GENE
+-	I-GENE
+kb	I-GENE
+CENP	I-GENE
+-	I-GENE
+A	I-GENE
+-	I-GENE
+binding	I-GENE
+DNA	I-GENE
+domain	I-GENE
+of	O
+a	O
+neocentromere	O
+derived	O
+from	O
+the	O
+20p12	O
+region	O
+of	O
+an	O
+invdup	O
+(	O
+20p	O
+)	O
+human	O
+marker	O
+chromosome	O
+.	O
+
+We	O
+describe	O
+a	O
+total	O
+of	O
+39	O
+DEAH	B-GENE
+helicases	I-GENE
+in	O
+these	O
+four	O
+species	O
+.	O
+
+Two	O
+cases	O
+with	O
+marked	O
+chronic	O
+arm	O
+lymphoedema	O
+reported	O
+major	O
+and	O
+persistent	O
+improvements	O
+in	O
+arm	O
+volume	O
+for	O
+at	O
+least	O
+12	O
+months	O
+after	O
+treatment	O
+with	O
+HBO2	O
+.	O
+
+The	O
+sensitivity	O
+of	O
+human	O
+neuroblastoma	O
+cells	O
+SK	O
+-	O
+N	O
+-	O
+SH	O
+to	O
+undergo	O
+apoptosis	O
+induced	O
+by	O
+thapsigargin	O
+was	O
+examined	O
+.	O
+
+Prophylactic	O
+lymph	O
+node	O
+dissection	O
+or	O
+radiation	O
+therapy	O
+to	O
+the	O
+nodal	O
+chain	O
+may	O
+decrease	O
+local	O
+recurrence	O
+but	O
+does	O
+not	O
+consistently	O
+affect	O
+overall	O
+survival	O
+.	O
+
+Currently	O
+,	O
+the	O
+clinical	O
+use	O
+of	O
+5	O
+-	O
+aminolaevulinic	O
+acid	O
+(	O
+ALA	O
+)	O
+induced	O
+protoporphyrin	B-GENE
+IX	I-GENE
+(	O
+PPIX	B-GENE
+)	O
+for	O
+photodynamic	O
+therapy	O
+(	O
+PDT	O
+)	O
+is	O
+limited	O
+by	O
+the	O
+maximum	O
+tolerated	O
+oral	O
+ALA	O
+dose	O
+(	O
+60	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+We	O
+can	O
+classify	O
+antibiotics	O
+into	O
+two	O
+groups	O
+based	O
+on	O
+initial	O
+bactericidal	O
+activity	O
+against	O
+P	O
+.	O
+aeruginosa	O
+;	O
+one	O
+class	O
+is	O
+antibiotics	O
+having	O
+rapid	O
+initial	O
+killing	O
+such	O
+as	O
+AMK	O
+,	O
+IPM	O
+and	O
+PAPM	O
+,	O
+the	O
+other	O
+is	O
+CAZ	O
+,	O
+MEPM	O
+showing	O
+slow	O
+initial	O
+killing	O
+.	O
+
+Managing	O
+HIV	O
+.	O
+
+In	O
+Klinefelter	O
+'	O
+s	O
+syndrome	O
+(	O
+47XXY	O
+)	O
+,	O
+serum	O
+testosterone	O
+levels	O
+are	O
+at	O
+the	O
+lower	O
+end	O
+of	O
+the	O
+normal	O
+range	O
+and	O
+dihydrotestosterone	O
+levels	O
+are	O
+low	O
+.	O
+
+The	O
+histamine	B-GENE
+H1	I-GENE
+receptor	I-GENE
+antagonists	O
+(	O
+antihistamines	O
+)	O
+are	O
+an	O
+important	O
+class	O
+of	O
+medications	O
+used	O
+for	O
+the	O
+relief	O
+of	O
+common	O
+symptoms	O
+associated	O
+with	O
+hyperhistaminic	O
+conditions	O
+occurring	O
+in	O
+children	O
+and	O
+adults	O
+.	O
+
+Conclusion	O
+:	O
+The	O
+Lp	B-GENE
+(	I-GENE
+a	I-GENE
+)	I-GENE
+levels	O
+in	O
+these	O
+children	O
+were	O
+the	O
+lower	O
+ever	O
+reported	O
+.	O
+
+A	O
+subset	O
+of	O
+patients	O
+(	O
+n	O
+=	O
+30	O
+)	O
+underwent	O
+multichannel	O
+pressure	O
+flow	O
+studies	O
+,	O
+which	O
+demonstrated	O
+that	O
+transrectal	O
+HIFU	O
+reduces	O
+bladder	O
+outflow	O
+obstruction	O
+.	O
+
+AIMS	O
+:	O
+To	O
+establish	O
+a	O
+baseline	O
+and	O
+intraindividual	O
+fluctuations	O
+of	O
+the	O
+tumour	O
+markers	O
+CEA	B-GENE
+,	O
+CA	B-GENE
+50	I-GENE
+and	O
+CA	B-GENE
+242	I-GENE
+in	O
+patients	O
+cured	O
+from	O
+colorectal	O
+cancer	O
+,	O
+and	O
+to	O
+test	O
+the	O
+hypothesis	O
+that	O
+serum	O
+concentrations	O
+and	O
+intraindividual	O
+fluctuations	O
+do	O
+not	O
+differ	O
+from	O
+the	O
+concentrations	O
+in	O
+cancer	O
+-	O
+free	O
+individuals	O
+.	O
+
+The	O
+homologous	O
+active	O
+-	O
+site	O
+framework	O
+of	O
+these	O
+enzymes	O
+with	O
+distinct	O
+structures	O
+suggests	O
+convergent	O
+evolution	O
+of	O
+a	O
+common	O
+catalytic	O
+mechanism	O
+.	O
+
+We	O
+found	O
+that	O
+RhoA	B-GENE
+can	O
+initiate	O
+a	O
+linear	O
+kinase	O
+cascade	O
+leading	O
+to	O
+the	O
+activation	O
+of	O
+ERK6	B-GENE
+(	O
+p38	B-GENE
+gamma	I-GENE
+)	O
+,	O
+a	O
+recently	O
+identified	O
+member	O
+of	O
+the	O
+p38	B-GENE
+family	I-GENE
+of	O
+MAPKs	O
+.	O
+
+We	O
+show	O
+that	O
+several	O
+heme	O
+-	O
+responsive	O
+mechanisms	O
+combine	O
+to	O
+regulate	O
+DAN	B-GENE
+/	O
+TIR	B-GENE
+gene	O
+expression	O
+.	O
+
+In	O
+strains	O
+lacking	O
+tup11	B-GENE
+and	O
+tup12	B-GENE
+,	O
+the	O
+atf1	B-GENE
+-	O
+pcr1	B-GENE
+transcriptional	O
+activator	O
+continues	O
+to	O
+play	O
+a	O
+central	O
+role	O
+in	O
+fbp1	B-GENE
+-	O
+lacZ	B-GENE
+expression	O
+;	O
+however	O
+,	O
+spc1	B-GENE
+MAPK	I-GENE
+phosphorylation	O
+of	O
+atf1	B-GENE
+is	O
+no	O
+longer	O
+essential	O
+for	O
+its	O
+activation	O
+.	O
+
+In	O
+vitro	O
+binding	O
+studies	O
+demonstrate	O
+that	O
+eIF	B-GENE
+-	I-GENE
+5A	I-GENE
+is	O
+required	O
+for	O
+efficient	O
+interaction	O
+of	O
+Rev	B-GENE
+-	O
+NES	B-GENE
+with	O
+CRM1	B-GENE
+/	O
+exportin1	B-GENE
+and	O
+that	O
+eIF	B-GENE
+-	I-GENE
+5A	I-GENE
+interacts	O
+with	O
+the	O
+nucleoporins	O
+CAN	B-GENE
+/	O
+nup214	B-GENE
+,	O
+nup153	B-GENE
+,	O
+nup98	B-GENE
+,	O
+and	O
+nup62	B-GENE
+.	O
+
+Structural	O
+studies	O
+have	O
+shown	O
+that	O
+class	B-GENE
+I	I-GENE
+major	I-GENE
+histocompatibility	I-GENE
+complex	I-GENE
+(	O
+MHC	B-GENE
+)	O
+-	O
+restricted	O
+peptide	O
+-	O
+specific	O
+T	B-GENE
+cell	I-GENE
+receptor	I-GENE
+(	I-GENE
+TCR	I-GENE
+)	I-GENE
+-	I-GENE
+alpha	I-GENE
+/	I-GENE
+betas	I-GENE
+make	O
+multiple	O
+contacts	O
+with	O
+the	O
+alpha1	O
+and	O
+alpha2	O
+helices	O
+of	O
+the	O
+MHC	B-GENE
+,	O
+but	O
+it	O
+is	O
+unclear	O
+which	O
+or	O
+how	O
+many	O
+of	O
+these	O
+interactions	O
+contribute	O
+to	O
+functional	O
+binding	O
+.	O
+
+Mice	O
+homozygous	O
+for	O
+the	O
+dlg	B-GENE
+mutation	O
+exhibit	O
+growth	O
+retardation	O
+in	O
+utero	O
+,	O
+have	O
+hypoplasia	O
+of	O
+the	O
+premaxilla	O
+and	O
+mandible	O
+,	O
+have	O
+a	O
+cleft	O
+secondary	O
+palate	O
+,	O
+and	O
+die	O
+perinatally	O
+.	O
+
+Moreover	O
+,	O
+a	O
+complex	O
+containing	O
+PTP	B-GENE
+phi	I-GENE
+,	O
+paxillin	B-GENE
+,	O
+and	O
+a	O
+paxillin	B-GENE
+-	I-GENE
+associated	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+,	O
+Pyk2	B-GENE
+,	O
+can	O
+be	O
+immunoprecipitated	O
+from	O
+macrophage	O
+lysates	O
+,	O
+and	O
+the	O
+catalytic	O
+domain	O
+of	O
+PTP	B-GENE
+phi	I-GENE
+selectively	O
+binds	O
+paxillin	B-GENE
+and	O
+Pyk2	B-GENE
+in	O
+vitro	O
+.	O
+
+A	O
+single	O
+base	O
+change	O
+(	O
+A8G	O
+)	O
+in	O
+either	O
+sequence	O
+reduces	O
+hnRNP	B-GENE
+A2	I-GENE
+binding	O
+and	O
+,	O
+in	O
+the	O
+case	O
+of	O
+A2RE	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+inhibits	O
+RNA	O
+transport	O
+.	O
+
+Baseline	O
+variables	O
+associated	O
+with	O
+CD	O
+included	O
+a	O
+less	O
+frequent	O
+use	O
+of	O
+prestroke	O
+aspirin	O
+and	O
+a	O
+higher	O
+incidence	O
+of	O
+early	O
+CT	O
+changes	O
+of	O
+edema	O
+or	O
+mass	O
+effect	O
+or	O
+dense	O
+middle	O
+cerebral	O
+artery	O
+sign	O
+.	O
+
+IL	B-GENE
+-	I-GENE
+1beta	I-GENE
+was	O
+significantly	O
+higher	O
+in	O
+endometrioma	O
+than	O
+in	O
+lesions	O
+of	O
+other	O
+localizations	O
+.	O
+
+A	O
+complete	O
+drug	O
+history	O
+was	O
+compiled	O
+,	O
+specifying	O
+the	O
+amount	O
+and	O
+duration	O
+of	O
+VGB	O
+medication	O
+.	O
+
+The	O
+mutant	O
+receptors	O
+,	O
+as	O
+well	O
+as	O
+sBMPR	B-GENE
+-	I-GENE
+IA	I-GENE
+,	O
+were	O
+expressed	O
+as	O
+fusion	O
+proteins	O
+with	O
+thioredoxin	B-GENE
+in	O
+Escherichia	O
+coli	O
+,	O
+and	O
+purified	O
+using	O
+reverse	O
+phase	O
+high	O
+performance	O
+liquid	O
+chromatography	O
+(	O
+RP	O
+-	O
+HPLC	O
+)	O
+after	O
+digestion	O
+with	O
+enterokinase	B-GENE
+.	O
+
+The	O
+authors	O
+undertook	O
+a	O
+retrospective	O
+analysis	O
+of	O
+pathology	O
+with	O
+quantification	O
+of	O
+the	O
+percentage	O
+of	O
+papillary	O
+serous	O
+component	O
+(	O
+%	O
+PSC	O
+)	O
+and	O
+p53	B-GENE
+expression	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+the	O
+immediate	O
+and	O
+the	O
+final	O
+(	O
+after	O
+swelling	O
+)	O
+fixation	O
+strengths	O
+of	O
+two	O
+variations	O
+of	O
+the	O
+swellable	O
+bone	O
+anchor	O
+designs	O
+(	O
+a	O
+smooth	O
+anchor	O
+and	O
+a	O
+screw	O
+anchor	O
+)	O
+were	O
+measured	O
+in	O
+two	O
+different	O
+foams	O
+(	O
+used	O
+to	O
+simulate	O
+bone	O
+)	O
+with	O
+different	O
+densities	O
+.	O
+
+Constitutive	O
+phosphorylation	O
+and	O
+nuclear	O
+localization	O
+of	O
+Smad3	B-GENE
+are	O
+correlated	O
+with	O
+increased	O
+collagen	B-GENE
+gene	I-GENE
+transcription	O
+in	O
+activated	O
+hepatic	O
+stellate	O
+cells	O
+.	O
+
+Cloning	O
+and	O
+characterization	O
+of	O
+the	O
+murine	B-GENE
+beta	I-GENE
+(	I-GENE
+3	I-GENE
+)	I-GENE
+integrin	I-GENE
+gene	I-GENE
+promoter	O
+:	O
+identification	O
+of	O
+an	O
+interleukin	B-GENE
+-	I-GENE
+4	I-GENE
+responsive	I-GENE
+element	I-GENE
+and	O
+regulation	O
+by	O
+STAT	B-GENE
+-	I-GENE
+6	I-GENE
+.	O
+
+CONCLUSIONS	O
+:	O
+Although	O
+the	O
+levels	O
+of	O
+oxLDL	B-GENE
+antibodies	I-GENE
+might	O
+be	O
+modified	O
+in	O
+early	O
+hypertension	O
+,	O
+once	O
+advanced	O
+coronary	O
+artery	O
+disease	O
+has	O
+developed	O
+the	O
+presence	O
+of	O
+hypertension	O
+does	O
+not	O
+affect	O
+anti	B-GENE
+-	I-GENE
+oxLDL	I-GENE
+levels	O
+.	O
+
+GafChromic	O
+(	O
+MD	O
+-	O
+55	O
+-	O
+2	O
+)	O
+radiochromic	O
+film	O
+has	O
+become	O
+increasingly	O
+popular	O
+for	O
+medical	O
+applications	O
+and	O
+has	O
+proven	O
+to	O
+be	O
+useful	O
+for	O
+brachytherapy	O
+dosimetry	O
+.	O
+
+RESULTS	O
+:	O
+Within	O
+7	O
+days	O
+,	O
+all	O
+groups	O
+re	O
+-	O
+acquired	O
+responding	O
+for	O
+heroin	O
+under	O
+CRF	O
+at	O
+rates	O
+similar	O
+to	O
+their	O
+pre	O
+-	O
+lesion	O
+performance	O
+.	O
+
+Cis	O
+-	O
+acting	O
+CCAAT	O
+elements	O
+are	O
+frequently	O
+found	O
+in	O
+eukaryotic	O
+promoter	O
+regions	O
+.	O
+
+Twenty	O
+-	O
+five	O
+patients	O
+also	O
+received	O
+PET	O
+examinations	O
+during	O
+the	O
+staging	O
+procedures	O
+.	O
+
+The	O
+Gap69C	B-GENE
+is	O
+a	O
+single	O
+-	O
+copy	O
+gene	O
+producing	O
+a	O
+major	O
+2	O
+.	O
+1	O
+-	O
+kb	O
+mRNA	O
+throughout	O
+development	O
+,	O
+but	O
+its	O
+amount	O
+is	O
+decreased	O
+in	O
+larvae	O
+.	O
+
+Cases	O
+of	O
+lung	O
+cancer	O
+with	O
+intramedullary	O
+metastasis	O
+are	O
+rare	O
+,	O
+especially	O
+those	O
+diagnosed	O
+before	O
+death	O
+.	O
+
+A	O
+novel	O
+growth	O
+-	O
+related	O
+nuclear	O
+protein	O
+binds	O
+and	O
+inhibits	O
+rat	O
+aldolase	B-GENE
+B	I-GENE
+gene	I-GENE
+promoter	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+investigate	O
+the	O
+association	O
+between	O
+complete	O
+congenital	O
+heart	O
+block	O
+(	O
+CCHB	O
+)	O
+in	O
+the	O
+fetus	O
+and	O
+adult	O
+disease	O
+.	O
+
+This	O
+study	O
+examined	O
+the	O
+role	O
+of	O
+cholesteryl	O
+ester	O
+transfer	O
+(	O
+CET	O
+)	O
+,	O
+cholesteryl	B-GENE
+ester	I-GENE
+transfer	I-GENE
+protein	I-GENE
+(	O
+CETP	B-GENE
+)	O
+activity	O
+,	O
+and	O
+phospholipid	B-GENE
+transfer	I-GENE
+protein	I-GENE
+(	O
+PLTP	B-GENE
+)	O
+activity	O
+in	O
+the	O
+increased	O
+prevalence	O
+of	O
+coronary	O
+artery	O
+calcification	O
+(	O
+CAC	O
+)	O
+in	O
+diabetic	O
+subjects	O
+compared	O
+with	O
+nondiabetic	O
+subjects	O
+and	O
+in	O
+the	O
+loss	O
+of	O
+the	O
+sex	O
+difference	O
+in	O
+CAC	O
+in	O
+diabetes	O
+.	O
+
+Two	O
+families	O
+with	O
+concordant	O
+inheritance	O
+of	O
+DNAH9	B-GENE
+alleles	I-GENE
+in	O
+affected	O
+individuals	O
+were	O
+observed	O
+.	O
+
+Efficacy	O
+of	O
+first	O
+-	O
+generation	O
+Cavermap	O
+to	O
+verify	O
+location	O
+and	O
+function	O
+of	O
+cavernous	O
+nerves	O
+during	O
+radical	O
+prostatectomy	O
+:	O
+a	O
+multi	O
+-	O
+institutional	O
+evaluation	O
+by	O
+experienced	O
+surgeons	O
+.	O
+
+The	O
+(	O
+two	O
+-	O
+motif	O
+)	O
+domain	O
+fold	O
+contains	O
+a	O
+pair	O
+of	O
+calcium	O
+binding	O
+sites	O
+very	O
+similar	O
+to	O
+those	O
+found	O
+in	O
+a	O
+two	B-GENE
+-	I-GENE
+domain	I-GENE
+prokaryotic	I-GENE
+betagamma	I-GENE
+-	I-GENE
+crystallin	I-GENE
+fold	I-GENE
+family	I-GENE
+member	I-GENE
+,	O
+Protein	B-GENE
+S	I-GENE
+.	O
+
+Deletional	O
+analyses	O
+of	O
+VDR	B-GENE
+indicated	O
+that	O
+GRIP1	B-GENE
+and	O
+RAC3	B-GENE
+required	O
+an	O
+intact	O
+VDR	B-GENE
+activation	O
+function	O
+(	O
+AF	O
+-	O
+2	O
+)	O
+domain	O
+for	O
+efficient	O
+interaction	O
+as	O
+well	O
+as	O
+additional	O
+but	O
+distinct	O
+regions	O
+of	O
+the	O
+VDR	B-GENE
+.	O
+
+Mechanism	O
+in	O
+the	O
+sequential	O
+control	O
+of	O
+cell	O
+morphology	O
+and	O
+S	O
+phase	O
+entry	O
+by	O
+epidermal	B-GENE
+growth	I-GENE
+factor	I-GENE
+involves	O
+distinct	O
+MEK	B-GENE
+/	O
+ERK	B-GENE
+activations	O
+.	O
+
+3D	O
+image	O
+-	O
+processing	O
+permits	O
+to	O
+analyse	O
+ultrasound	O
+data	O
+interactively	O
+in	O
+three	O
+orthogonal	O
+planes	O
+(	O
+section	O
+mode	O
+)	O
+or	O
+in	O
+realistic	O
+3D	O
+views	O
+(	O
+rendering	O
+mode	O
+)	O
+.	O
+
+Direct	O
+superoxide	O
+scavenging	O
+activity	O
+of	O
+nonsteroidal	O
+anti	O
+-	O
+inflammatory	O
+drugs	O
+:	O
+determination	O
+by	O
+electron	O
+spin	O
+resonance	O
+using	O
+the	O
+spin	O
+trap	O
+method	O
+.	O
+
+BACKGROUND	O
+:	O
+Dermoscopy	O
+is	O
+a	O
+noninvasive	O
+technique	O
+that	O
+increases	O
+the	O
+diagnostic	O
+accuracy	O
+of	O
+pigmented	O
+skin	O
+lesions	O
+,	O
+particularly	O
+improving	O
+the	O
+diagnosis	O
+of	O
+patients	O
+with	O
+cutaneous	O
+melanoma	O
+in	O
+situ	O
+(	O
+CMIS	O
+)	O
+and	O
+early	O
+invasive	O
+melanoma	O
+.	O
+
+Moreover	O
+,	O
+PTax	B-GENE
+expressed	O
+higher	O
+background	O
+activities	O
+than	O
+PTF	B-GENE
+,	O
+indicating	O
+that	O
+the	O
+sequence	O
+of	O
+the	O
+synthetic	O
+regulatory	O
+region	O
+can	O
+influence	O
+background	O
+levels	O
+.	O
+
+However	O
+,	O
+the	O
+promoter	O
+region	O
+contains	O
+several	O
+potential	O
+cis	O
+-	O
+regulatory	O
+elements	O
+such	O
+as	O
+Sp1	B-GENE
+,	O
+early	B-GENE
+growth	I-GENE
+response	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+activator	B-GENE
+protein	I-GENE
+-	I-GENE
+2	I-GENE
+,	O
+MyoD	B-GENE
+,	O
+p300	B-GENE
+,	O
+nuclear	B-GENE
+factor	I-GENE
+-	I-GENE
+kappaB	I-GENE
+,	O
+myeloid	B-GENE
+zinc	I-GENE
+finger	I-GENE
+protein	I-GENE
+-	I-GENE
+1	I-GENE
+,	O
+caudal	B-GENE
+-	I-GENE
+related	I-GENE
+homeobox	I-GENE
+(	I-GENE
+Cdx	I-GENE
+)	I-GENE
+gene	I-GENE
+A	I-GENE
+,	O
+and	O
+Cdx	B-GENE
+protein	I-GENE
+-	I-GENE
+2	I-GENE
+binding	I-GENE
+sites	I-GENE
+.	O
+
+Thus	O
+,	O
+the	O
+interaction	O
+of	O
+Tat	B-GENE
+with	O
+the	O
+components	O
+of	O
+this	O
+rel	B-GENE
+/	O
+AP1	B-GENE
+cooperative	O
+complex	O
+seems	O
+to	O
+induce	O
+quantitative	O
+and	O
+qualitative	O
+alterations	O
+of	O
+this	O
+complex	O
+as	O
+activation	O
+progresses	O
+,	O
+resulting	O
+in	O
+a	O
+decrease	O
+of	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+gene	I-GENE
+transcription	O
+.	O
+
+2001	O
+.	O
+
+Unlike	O
+other	O
+progenitor	O
+cells	O
+of	O
+the	O
+brain	O
+,	O
+SVZa	O
+progenitor	O
+cells	O
+have	O
+the	O
+capacity	O
+to	O
+divide	O
+even	O
+though	O
+they	O
+express	O
+a	O
+neuronal	O
+phenotype	O
+.	O
+
+A	O
+minimal	O
+ER3	O
+sequence	O
+of	O
+DNA	O
+was	O
+further	O
+demonstrated	O
+to	O
+function	O
+as	O
+a	O
+FXR	B-GENE
+HRE	I-GENE
+and	O
+was	O
+bound	O
+in	O
+vitro	O
+by	O
+FXR	B-GENE
+-	O
+expressing	O
+yeast	O
+extracts	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+determine	O
+the	O
+association	O
+of	O
+depressive	O
+symptoms	O
+with	O
+HIV	O
+-	O
+related	O
+mortality	O
+and	O
+decline	O
+in	O
+CD4	B-GENE
+lymphocyte	O
+counts	O
+among	O
+women	O
+with	O
+HIV	O
+.	O
+
+An	O
+economic	O
+analysis	O
+using	O
+West	O
+of	O
+Scotland	O
+Coronary	O
+Prevention	O
+Study	O
+(	O
+WOSCOPS	O
+)	O
+findings	O
+indicates	O
+that	O
+statin	B-GENE
+treatment	O
+would	O
+have	O
+prevented	O
+318	O
+events	O
+per	O
+10	O
+,	O
+000	O
+patients	O
+in	O
+a	O
+population	O
+similar	O
+to	O
+that	O
+in	O
+WOSCOPS	O
+(	O
+average	O
+1	O
+.	O
+5	O
+%	O
+annual	O
+risk	O
+of	O
+a	O
+cardiovascular	O
+event	O
+)	O
+at	O
+a	O
+discounted	O
+cost	O
+per	O
+life	O
+-	O
+year	O
+gained	O
+of	O
+20	O
+,	O
+375	O
+pounds	O
+(	O
+$	O
+31	O
+,	O
+818	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+soluble	O
+forms	O
+of	O
+ATF6	B-GENE
+and	O
+the	O
+G13	B-GENE
+gene	I-GENE
+product	I-GENE
+are	O
+unable	O
+to	O
+bind	O
+to	O
+several	O
+point	O
+mutants	O
+of	O
+the	O
+cis	O
+-	O
+acting	O
+ER	O
+stress	O
+response	O
+element	O
+in	O
+vitro	O
+that	O
+hardly	O
+respond	O
+to	O
+ER	O
+stress	O
+in	O
+vivo	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+initiated	O
+to	O
+explore	O
+the	O
+potential	O
+of	O
+a	O
+hybrid	O
+biological	O
+reactor	O
+,	O
+combining	O
+trickling	O
+filter	O
+(	O
+TF	O
+)	O
+and	O
+activated	O
+sludge	O
+process	O
+(	O
+ASP	O
+)	O
+,	O
+to	O
+treat	O
+wastewater	O
+containing	O
+trichloroethylene	O
+(	O
+TCE	O
+)	O
+at	O
+ambient	O
+temperature	O
+at	O
+different	O
+hydraulic	O
+retention	O
+time	O
+(	O
+HRT	O
+)	O
+.	O
+
+In	O
+DNA	O
+strand	O
+exchange	O
+reactions	O
+using	O
+oligonucleotides	O
+,	O
+we	O
+found	O
+that	O
+Rec2	B-GENE
+exhibited	O
+a	O
+pairing	O
+bias	O
+that	O
+is	O
+opposite	O
+that	O
+of	O
+RecA	B-GENE
+.	O
+
+Forskolin	O
+treatment	O
+(	O
+10	O
+microM	O
+)	O
+of	O
+the	O
+transfected	O
+cells	O
+for	O
+3	O
+-	O
+-	O
+6	O
+h	O
+maximally	O
+induced	O
+luciferase	B-GENE
+threefold	O
+.	O
+
+Analysis	O
+of	O
+ace2Delta	O
+cells	O
+reveals	O
+that	O
+Ace2p	B-GENE
+is	O
+required	O
+for	O
+cell	O
+separation	O
+but	O
+not	O
+for	O
+polarized	O
+growth	O
+.	O
+
+The	O
+results	O
+presented	O
+here	O
+show	O
+that	O
+AR1	B-GENE
+of	O
+the	O
+promoter	O
+-	O
+proximal	O
+CAP	B-GENE
+subunit	I-GENE
+was	O
+required	O
+for	O
+papBA	B-GENE
+transcription	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+the	O
+histone	B-GENE
+-	I-GENE
+like	I-GENE
+protein	I-GENE
+H	B-GENE
+-	I-GENE
+NS	I-GENE
+.	O
+
+A	O
+.	O
+,	O
+Slatkin	O
+,	O
+D	O
+.	O
+
+RESULTS	O
+:	O
+A	O
+significant	O
+correlation	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+was	O
+observed	O
+for	O
+mean	O
+wall	O
+thickness	O
+and	O
+vessel	O
+wall	O
+area	O
+between	O
+MRI	O
+and	O
+histopathology	O
+(	O
+r	O
+=	O
+0	O
+.	O
+87	O
+and	O
+r	O
+=	O
+0	O
+.	O
+85	O
+,	O
+respectively	O
+)	O
+.	O
+
+Our	O
+data	O
+indicate	O
+that	O
+SIP1	B-GENE
+is	O
+required	O
+to	O
+confine	O
+XBra	B-GENE
+gene	I-GENE
+expression	O
+to	O
+the	O
+mesoderm	O
+.	O
+
+SIP1	B-GENE
+(	O
+Smad	B-GENE
+interacting	I-GENE
+protein	I-GENE
+1	I-GENE
+)	O
+and	O
+deltaEF1	B-GENE
+(	O
+delta	B-GENE
+-	I-GENE
+crystallin	I-GENE
+enhancer	I-GENE
+binding	I-GENE
+factor	I-GENE
+)	O
+are	O
+structurally	O
+similar	O
+transcriptional	O
+repressors	O
+.	O
+
+B	B-GENE
+-	I-GENE
+myb	I-GENE
+is	O
+essential	O
+for	O
+G1	O
+/	O
+S	O
+transition	O
+and	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+phosphorylated	O
+by	O
+the	O
+cyclin	B-GENE
+A2	I-GENE
+/	O
+cdk2	B-GENE
+complex	O
+.	O
+
+Nucleotide	O
+sequence	O
+,	O
+transcription	O
+map	O
+,	O
+and	O
+mutation	O
+analysis	O
+of	O
+the	O
+13q14	O
+chromosomal	O
+region	O
+deleted	O
+in	O
+B	O
+-	O
+cell	O
+chronic	O
+lymphocytic	O
+leukemia	O
+.	O
+
+Human	B-GENE
+T	I-GENE
+-	I-GENE
+cell	I-GENE
+leukemia	I-GENE
+virus	I-GENE
+type	I-GENE
+I	I-GENE
+(	I-GENE
+HTLV	I-GENE
+-	I-GENE
+I	I-GENE
+)	I-GENE
+Tax	I-GENE
+is	O
+a	O
+potent	O
+transcriptional	O
+regulator	O
+that	O
+can	O
+activate	O
+or	O
+repress	O
+specific	O
+cellular	O
+genes	O
+and	O
+that	O
+has	O
+been	O
+proposed	O
+to	O
+contribute	O
+to	O
+leukemogenesis	O
+in	O
+adult	O
+T	O
+-	O
+cell	O
+leukemia	O
+.	O
+
+Requirements	O
+for	O
+the	O
+nuclear	O
+-	O
+cytoplasmic	O
+translocation	O
+of	O
+infected	B-GENE
+-	I-GENE
+cell	I-GENE
+protein	I-GENE
+0	I-GENE
+of	O
+herpes	O
+simplex	O
+virus	O
+1	O
+.	O
+
+The	O
+Novacor	O
+Left	O
+Ventricular	O
+Assist	O
+System	O
+(	O
+LVAS	O
+)	O
+(	O
+Novacor	O
+Corp	O
+,	O
+Oakland	O
+,	O
+CA	O
+)	O
+was	O
+initially	O
+console	O
+-	O
+based	O
+and	O
+has	O
+been	O
+available	O
+since	O
+1993	O
+in	O
+a	O
+wearable	O
+configuration	O
+.	O
+
+Atheroma	O
+appears	O
+as	O
+a	O
+very	O
+low	O
+signal	O
+intensity	O
+area	O
+on	O
+2	O
+-	O
+dimensional	O
+time	O
+-	O
+of	O
+-	O
+flight	O
+(	O
+TOF	O
+)	O
+magnetic	O
+resonance	O
+(	O
+MR	O
+)	O
+images	O
+,	O
+and	O
+its	O
+components	O
+have	O
+various	O
+signal	O
+intensities	O
+on	O
+spin	O
+-	O
+echo	O
+(	O
+SE	O
+)	O
+images	O
+.	O
+
+Body	O
+fat	O
+distribution	O
+was	O
+determined	O
+by	O
+abdominal	O
+computed	O
+tomography	O
+.	O
+
+The	O
+flux	O
+rates	O
+of	O
+p	O
+-	O
+toluidine	O
+decreased	O
+as	O
+the	O
+pH	O
+value	O
+in	O
+the	O
+donor	O
+solution	O
+increased	O
+.	O
+
+The	O
+protein	O
+is	O
+composed	O
+of	O
+two	O
+major	O
+domains	O
+separated	O
+by	O
+a	O
+hydrophobic	O
+linker	O
+region	O
+of	O
+20	O
+amino	O
+acid	O
+residues	O
+.	O
+
+We	O
+performed	O
+the	O
+present	O
+study	O
+to	O
+clarify	O
+the	O
+relationship	O
+between	O
+the	O
+DOX	O
+binding	O
+ability	O
+(	O
+%	O
+DB	O
+)	O
+and	O
+the	O
+histologic	O
+response	O
+,	O
+rate	O
+of	O
+decrease	O
+in	O
+tumor	O
+volume	O
+of	O
+malignant	O
+soft	O
+tissue	O
+tumors	O
+after	O
+preoperative	O
+chemotherapy	O
+and	O
+prognosis	O
+.	O
+
+To	O
+avoid	O
+misinterpretations	O
+,	O
+special	O
+reference	O
+values	O
+should	O
+be	O
+applied	O
+for	O
+preadolescents	O
+,	O
+at	O
+least	O
+with	O
+regard	O
+to	O
+FVC	O
+and	O
+FEV1	O
+.	O
+
+Nephrotoxicity	O
+after	O
+orthotopic	O
+liver	O
+transplantation	O
+in	O
+cyclosporin	O
+A	O
+and	O
+FK	O
+506	O
+-	O
+treated	O
+patients	O
+.	O
+
+Compared	O
+with	O
+normal	O
+control	O
+subjects	O
+,	O
+all	O
+74	O
+TOF	O
+patients	O
+had	O
+decreased	O
+systolic	O
+and	O
+diastolic	O
+myocardial	O
+velocities	O
+and	O
+a	O
+longer	O
+isovolumic	O
+relaxation	O
+time	O
+.	O
+
+Acetoin	O
+can	O
+be	O
+reused	O
+by	O
+the	O
+bacteria	O
+during	O
+stationary	O
+phase	O
+when	O
+other	O
+carbon	O
+sources	O
+have	O
+been	O
+depleted	O
+.	O
+
+Mutational	O
+analysis	O
+showed	O
+that	O
+the	O
+U	O
+-	O
+box	O
+,	O
+like	O
+the	O
+RING	O
+finger	O
+in	O
+other	O
+proteins	O
+,	O
+forms	O
+the	O
+physical	O
+basis	O
+for	O
+the	O
+interaction	O
+with	O
+E2	B-GENE
+enzymes	I-GENE
+.	O
+
+Thus	O
+,	O
+our	O
+studies	O
+define	O
+Rac	B-GENE
+/	O
+Cdc42	B-GENE
+/	O
+Pak	B-GENE
+as	O
+a	O
+module	O
+upstream	O
+of	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+during	O
+its	O
+activation	O
+by	O
+microtubule	O
+disruption	O
+.	O
+
+Nrf2	B-GENE
+regulates	O
+expression	O
+of	O
+genes	O
+encoding	O
+enzymes	O
+with	O
+antioxidant	O
+(	O
+e	O
+.	O
+g	O
+.	O
+heme	B-GENE
+oxygenase	I-GENE
+-	I-GENE
+1	I-GENE
+(	O
+HO	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+)	O
+or	O
+xenobiotic	O
+detoxification	O
+(	O
+e	O
+.	O
+g	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+ATF4	B-GENE
+regulates	O
+basal	O
+and	O
+CdCl	O
+(	O
+2	O
+)	O
+-	O
+induced	O
+expression	O
+of	O
+the	O
+ho	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+in	O
+a	O
+cell	O
+-	O
+specific	O
+manner	O
+and	O
+possibly	O
+in	O
+a	O
+complex	O
+with	O
+Nrf2	B-GENE
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+forced	O
+overexpression	O
+of	O
+the	O
+wild	O
+type	O
+,	O
+but	O
+not	O
+the	O
+kinase	O
+-	O
+inactivated	O
+mutant	O
+of	O
+nm23H1	B-GENE
+,	O
+converted	O
+the	O
+GDP	O
+-	O
+bound	O
+forms	O
+of	O
+Rac1	B-GENE
+,	O
+Cdc42	B-GENE
+,	O
+and	O
+RhoA	B-GENE
+to	O
+their	O
+GTP	O
+-	O
+bound	O
+forms	O
+in	O
+vitro	O
+by	O
+its	O
+nucleoside	B-GENE
+diphosphate	I-GENE
+kinase	I-GENE
+activity	O
+,	O
+but	O
+nm23H1	B-GENE
+alone	O
+apparently	O
+did	O
+not	O
+produce	O
+the	O
+GTP	O
+-	O
+bound	O
+form	O
+of	O
+these	O
+GTPases	B-GENE
+in	O
+vivo	O
+.	O
+
+This	O
+effect	O
+was	O
+observed	O
+in	O
+the	O
+absence	O
+of	O
+de	O
+novo	O
+protein	O
+synthesis	O
+and	O
+was	O
+independent	O
+of	O
+histone	B-GENE
+deacetylase	I-GENE
+activity	O
+.	O
+
+Deletion	O
+of	O
+the	O
+potential	O
+initiator	O
+element	O
+does	O
+not	O
+affect	O
+repression	O
+of	O
+the	O
+p21	B-GENE
+promoter	I-GENE
+by	O
+c	B-GENE
+-	I-GENE
+Myc	I-GENE
+.	O
+
+Fetal	O
+lung	O
+volume	O
+:	O
+estimation	O
+at	O
+MR	O
+imaging	O
+-	O
+initial	O
+results	O
+.	O
+
+Of	O
+its	O
+gene	O
+products	O
+,	O
+E6	B-GENE
+binds	O
+to	O
+and	O
+inactivates	O
+p53	B-GENE
+tumor	I-GENE
+suppressor	I-GENE
+protein	I-GENE
+by	O
+ubiquitin	B-GENE
+/	O
+proteasome	O
+-	O
+dependent	O
+degradation	O
+.	O
+
+In	O
+mouse	O
+,	O
+Mmip1	B-GENE
+(	O
+Mad	B-GENE
+member	I-GENE
+interacting	I-GENE
+protein	I-GENE
+1	I-GENE
+)	O
+and	O
+Smc3	B-GENE
+share	O
+99	O
+%	O
+sequence	O
+identity	O
+and	O
+are	O
+products	O
+of	O
+the	O
+same	O
+gene	O
+.	O
+
+An	O
+element	O
+within	O
+the	O
+5	O
+'	O
+untranslated	O
+region	O
+of	O
+human	B-GENE
+Hsp70	I-GENE
+mRNA	I-GENE
+which	O
+acts	O
+as	O
+a	O
+general	O
+enhancer	O
+of	O
+mRNA	O
+translation	O
+.	O
+
+In	O
+SN	O
+-	O
+48	O
+neuronal	O
+cells	O
+that	O
+express	O
+MR	B-GENE
+,	O
+GR	B-GENE
+,	O
+and	O
+5	B-GENE
+-	I-GENE
+HT1A	I-GENE
+receptors	I-GENE
+,	O
+deletion	O
+or	O
+inactivation	O
+of	O
+the	O
+nGRE	O
+(	O
+negative	O
+GRE	O
+)	O
+eliminated	O
+negative	O
+regulation	O
+of	O
+the	O
+rat	B-GENE
+5	I-GENE
+-	I-GENE
+HT1A	I-GENE
+or	O
+heterologous	O
+promoters	O
+by	O
+corticosteroids	O
+,	O
+whereas	O
+its	O
+inclusion	O
+conferred	O
+corticosteroid	O
+-	O
+induced	O
+inhibition	O
+to	O
+a	O
+heterologous	O
+promoter	O
+.	O
+
+Corticosteroid	O
+-	O
+mediated	O
+transcriptional	O
+inhibition	O
+was	O
+greater	O
+for	O
+MR	B-GENE
+/	O
+GR	B-GENE
+in	O
+combination	O
+than	O
+for	O
+MR	B-GENE
+or	O
+GR	B-GENE
+alone	O
+.	O
+
+Whereas	O
+Smad2	B-GENE
+was	O
+rapidly	O
+phosphorylated	O
+by	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+and	O
+involved	O
+in	O
+the	O
+initial	O
+activation	O
+of	O
+Agc	B-GENE
+expression	O
+in	O
+confluent	O
+cells	O
+,	O
+Smad2	B-GENE
+activation	O
+was	O
+not	O
+required	O
+for	O
+maintaining	O
+the	O
+high	O
+level	O
+of	O
+Agc	B-GENE
+expression	O
+.	O
+
+Reverse	B-GENE
+transcriptase	I-GENE
+-	O
+polymerase	O
+chain	O
+reaction	O
+assays	O
+showed	O
+that	O
+PKRDeltaE7	B-GENE
+is	O
+expressed	O
+in	O
+a	O
+broad	O
+range	O
+of	O
+human	O
+tissues	O
+at	O
+variable	O
+levels	O
+.	O
+
+Both	O
+pancreatic	O
+and	O
+intestinal	O
+cell	O
+lines	O
+were	O
+found	O
+to	O
+express	O
+a	O
+number	O
+of	O
+POU	B-GENE
+(	O
+OCT	B-GENE
+binding	O
+)	O
+homeodomain	O
+proteins	O
+examined	O
+by	O
+electrophoretic	O
+mobility	O
+shift	O
+assay	O
+.	O
+
+SV1	B-GENE
+has	O
+a	O
+33	O
+-	O
+amino	O
+acid	O
+insert	O
+in	O
+the	O
+S1	O
+transmembrane	O
+domain	O
+that	O
+does	O
+not	O
+alter	O
+S1	O
+overall	O
+hydrophobicity	O
+,	O
+but	O
+makes	O
+the	O
+S0	O
+-	O
+S1	O
+linker	O
+longer	O
+.	O
+
+Polyclonal	O
+antibodies	O
+against	O
+the	O
+N	O
+-	O
+terminal	O
+part	O
+(	O
+amino	O
+acids	O
+12	O
+-	O
+363	O
+)	O
+and	O
+the	O
+C	O
+-	O
+terminal	O
+part	O
+(	O
+amino	O
+acids	O
+330	O
+-	O
+730	O
+)	O
+of	O
+rainbow	B-GENE
+trout	I-GENE
+HIF	I-GENE
+-	I-GENE
+1alpha	I-GENE
+protein	I-GENE
+recognized	O
+rainbow	B-GENE
+trout	I-GENE
+and	I-GENE
+chinook	I-GENE
+salmon	I-GENE
+HIF	I-GENE
+-	I-GENE
+1alpha	I-GENE
+protein	I-GENE
+in	O
+Western	O
+blot	O
+analysis	O
+.	O
+
+The	O
+v	B-GENE
+-	I-GENE
+Src	I-GENE
+SH3	B-GENE
+domain	I-GENE
+facilitates	O
+a	O
+cell	O
+adhesion	O
+-	O
+independent	O
+association	O
+with	O
+focal	B-GENE
+adhesion	I-GENE
+kinase	I-GENE
+.	O
+
+Mutagenesis	O
+of	O
+SNT1	B-GENE
+(	O
+IRS	B-GENE
+)	O
+CX	B-GENE
+identified	O
+three	O
+classes	O
+of	O
+effector	O
+motifs	O
+within	O
+SNT	B-GENE
+critical	O
+for	O
+both	O
+sustained	O
+ERK	B-GENE
+activation	O
+and	O
+neuronal	O
+differentiation	O
+:	O
+1	O
+)	O
+four	O
+phosphotyrosine	O
+motifs	O
+that	O
+mediate	O
+recruitment	O
+of	O
+Grb2	B-GENE
+,	O
+2	O
+)	O
+two	O
+phosphotyrosine	O
+motifs	O
+that	O
+mediate	O
+recruitment	O
+of	O
+Shp2	B-GENE
+,	O
+and	O
+3	O
+)	O
+a	O
+C	O
+-	O
+terminal	O
+motif	O
+that	O
+functions	O
+by	O
+helping	O
+to	O
+recruit	O
+Sos	B-GENE
+.	O
+
+Exchanging	O
+the	O
+human	O
+propeptide	O
+in	O
+this	O
+chimera	O
+with	O
+either	O
+the	O
+murine	B-GENE
+MIC	I-GENE
+-	I-GENE
+1	I-GENE
+or	O
+TGF	B-GENE
+-	I-GENE
+beta1	I-GENE
+propeptide	I-GENE
+resulted	O
+in	O
+secretion	O
+of	O
+the	O
+unprocessed	O
+,	O
+monomeric	O
+chimera	O
+,	O
+suggesting	O
+a	O
+specific	O
+interaction	O
+between	O
+the	O
+human	B-GENE
+MIC	I-GENE
+-	I-GENE
+1	I-GENE
+propeptide	I-GENE
+and	O
+mature	O
+peptide	O
+.	O
+
+Radiolabeled	O
+biantennary	O
+N	O
+-	O
+glycans	O
+synthesized	O
+by	O
+Pro	O
+(	O
+-	O
+)	O
+5Lec20	O
+were	O
+proportionately	O
+less	O
+ricin	O
+-	O
+bound	O
+than	O
+similar	O
+species	O
+from	O
+parental	O
+CHO	O
+cells	O
+,	O
+and	O
+Lec20	O
+cell	O
+extracts	O
+had	O
+a	O
+markedly	O
+reduced	O
+ability	O
+to	O
+transfer	O
+Gal	O
+to	O
+GlcNAc	O
+-	O
+terminating	O
+acceptors	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+SOCS	B-GENE
+box	I-GENE
+interacted	O
+with	O
+Cullin	B-GENE
+-	I-GENE
+2	I-GENE
+and	O
+promoted	O
+ubiquitination	O
+of	O
+TEL	B-GENE
+-	O
+JAK2	B-GENE
+.	O
+
+Neuron	B-GENE
+-	I-GENE
+specific	I-GENE
+Bcl	I-GENE
+-	I-GENE
+2	I-GENE
+homology	I-GENE
+3	I-GENE
+domain	I-GENE
+-	I-GENE
+only	I-GENE
+splice	I-GENE
+variant	I-GENE
+of	O
+Bak	B-GENE
+is	O
+anti	O
+-	O
+apoptotic	O
+in	O
+neurons	O
+,	O
+but	O
+pro	O
+-	O
+apoptotic	O
+in	O
+non	O
+-	O
+neuronal	O
+cells	O
+.	O
+
+Sequence	O
+comparison	O
+and	O
+binding	O
+studies	O
+of	O
+the	O
+18	B-GENE
+-	I-GENE
+bp	I-GENE
+MOK2	I-GENE
+-	I-GENE
+binding	I-GENE
+sites	I-GENE
+present	O
+in	O
+intron	O
+2	O
+of	O
+human	O
+,	O
+bovine	O
+,	O
+and	O
+mouse	B-GENE
+IRBP	I-GENE
+genes	I-GENE
+show	O
+that	O
+the	O
+3	O
+'	O
+-	O
+half	O
+sequence	O
+is	O
+the	O
+essential	O
+core	O
+element	O
+for	O
+MOK2	B-GENE
+binding	O
+.	O
+
+Furthermore	O
+,	O
+SB203580	O
+inhibited	O
+LPS	O
+-	O
+induced	O
+activation	O
+of	O
+Sp1	B-GENE
+,	O
+as	O
+well	O
+as	O
+the	O
+promoter	O
+activity	O
+in	O
+cells	O
+transfected	O
+with	O
+a	O
+plasmid	O
+containing	O
+the	O
+Sp1	B-GENE
+consensus	O
+sequence	O
+.	O
+
+We	O
+confirmed	O
+the	O
+interaction	O
+between	O
+TLS	B-GENE
+and	O
+p65	B-GENE
+by	O
+the	O
+pull	O
+-	O
+down	O
+assay	O
+in	O
+vitro	O
+and	O
+by	O
+a	O
+coimmunoprecipitation	O
+experiment	O
+followed	O
+by	O
+Western	O
+blot	O
+of	O
+the	O
+cultured	O
+cell	O
+in	O
+vivo	O
+.	O
+
+Based	O
+on	O
+mutational	O
+data	O
+and	O
+possible	O
+mRNA	O
+structure	O
+,	O
+we	O
+hypothesized	O
+about	O
+the	O
+effect	O
+of	O
+mRNA	O
+structure	O
+on	O
+translation	O
+of	O
+the	O
+two	O
+major	O
+C	B-GENE
+/	I-GENE
+EBPepsilon	I-GENE
+isoforms	I-GENE
+:	O
+p32	B-GENE
+and	O
+p30	B-GENE
+.	O
+
+Binding	O
+of	O
+serum	B-GENE
+response	I-GENE
+factor	I-GENE
+to	O
+CArG	O
+box	O
+sequences	O
+is	O
+necessary	O
+but	O
+not	O
+sufficient	O
+to	O
+restrict	O
+gene	O
+expression	O
+to	O
+arterial	O
+smooth	O
+muscle	O
+cells	O
+.	O
+
+Together	O
+,	O
+these	O
+results	O
+identify	O
+HPK1	B-GENE
+as	O
+a	O
+new	O
+component	O
+of	O
+TCR	B-GENE
+signaling	O
+.	O
+
+The	O
+size	O
+of	O
+the	O
+infarct	O
+was	O
+determined	O
+using	O
+the	O
+creatine	B-GENE
+kinase	I-GENE
+integral	O
+method	O
+.	O
+
+A	O
+new	O
+echocardiographic	O
+technique	O
+is	O
+described	O
+with	O
+a	O
+conventional	O
+M	O
+mode	O
+,	O
+digitalised	O
+2D	O
+and	O
+tissular	O
+Doppler	O
+which	O
+has	O
+a	O
+comparable	O
+ability	O
+to	O
+identify	O
+the	O
+anomalous	O
+pathways	O
+of	O
+electric	O
+conduction	O
+using	O
+a	O
+non	O
+-	O
+invasive	O
+method	O
+.	O
+
+SELECTION	O
+CRITERIA	O
+:	O
+Randomised	O
+controlled	O
+trials	O
+of	O
+cabergoline	O
+versus	O
+placebo	O
+in	O
+patients	O
+with	O
+a	O
+clinical	O
+diagnosis	O
+of	O
+idiopathic	O
+Parkinson	O
+'	O
+s	O
+disease	O
+and	O
+long	O
+-	O
+term	O
+complications	O
+of	O
+levodopa	O
+therapy	O
+.	O
+
+Deterministic	O
+effects	O
+.	O
+
+Unusual	O
+two	B-GENE
+-	I-GENE
+domain	I-GENE
+arginine	I-GENE
+kinases	I-GENE
+(	O
+AKs	B-GENE
+)	O
+arose	O
+independently	O
+at	O
+least	O
+two	O
+times	O
+during	O
+molecular	O
+evolution	O
+of	O
+phosphagen	B-GENE
+kinases	I-GENE
+:	O
+AKs	B-GENE
+from	O
+the	O
+primitive	O
+sea	O
+anemone	O
+Anthopleurura	O
+japonicus	O
+and	O
+from	O
+the	O
+clam	O
+Pseudocardium	O
+sachalinensis	O
+.	O
+
+The	O
+mouse	B-GENE
+platelet	I-GENE
+-	I-GENE
+derived	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	I-GENE
+PDGF	I-GENE
+)	I-GENE
+beta	I-GENE
+-	I-GENE
+receptor	I-GENE
+promoter	I-GENE
+contains	O
+a	O
+CCAAT	O
+motif	O
+,	O
+and	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+plays	O
+an	O
+essential	O
+role	O
+in	O
+its	O
+transcription	O
+.	O
+
+Baseline	O
+MBF	O
+in	O
+females	O
+was	O
+significantly	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+higher	O
+than	O
+in	O
+males	O
+.	O
+
+No	O
+preferential	O
+VH	B-GENE
+/	O
+VL	B-GENE
+-	O
+chains	O
+correlated	O
+with	O
+any	O
+of	O
+the	O
+12	O
+different	O
+antigen	O
+reactivities	O
+,	O
+even	O
+for	O
+mAbs	O
+with	O
+nearly	O
+identical	O
+cross	O
+-	O
+reactivities	O
+.	O
+
+Recently	O
+,	O
+it	O
+was	O
+shown	O
+that	O
+purified	O
+RAG1	B-GENE
+/	I-GENE
+2	I-GENE
+proteins	I-GENE
+can	O
+cleave	O
+DNA	O
+hairpins	O
+in	O
+vitro	O
+,	O
+but	O
+the	O
+same	O
+activity	O
+was	O
+also	O
+described	O
+for	O
+a	O
+protein	O
+complex	O
+of	O
+the	O
+DNA	O
+repair	O
+proteins	O
+Nbs1	B-GENE
+/	O
+Mre11	B-GENE
+/	O
+Rad50	B-GENE
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+did	O
+not	O
+detect	O
+significant	O
+differences	O
+in	O
+CDR3	B-GENE
+sequences	I-GENE
+of	O
+endogenous	B-GENE
+Ig	I-GENE
+lambdaL	I-GENE
+and	O
+kappaL	B-GENE
+chain	I-GENE
+gene	I-GENE
+loci	I-GENE
+cloned	O
+from	O
+peripheral	O
+blood	O
+lymphocytes	O
+of	O
+an	O
+NBS	O
+patient	O
+and	O
+of	O
+healthy	O
+individuals	O
+.	O
+
+Phase	O
+II	O
+study	O
+of	O
+paclitaxel	O
+and	O
+oral	O
+etoposide	O
+in	O
+patients	O
+with	O
+locally	O
+advanced	O
+or	O
+metastatic	O
+non	O
+-	O
+small	O
+cell	O
+lung	O
+cancer	O
+.	O
+
+Oral	O
+supplementation	O
+of	O
+L	O
+-	O
+arginine	O
+significantly	O
+increased	O
+plasma	O
+L	O
+-	O
+citrulline	O
+,	O
+which	O
+indicated	O
+enhancement	O
+of	O
+NO	O
+production	O
+.	O
+
+This	O
+activation	O
+was	O
+then	O
+blocked	O
+by	O
+CGS	O
+12066A	O
+.	O
+
+Two	O
+independent	O
+transgenic	O
+lines	O
+were	O
+produced	O
+,	O
+and	O
+both	O
+showed	O
+expression	O
+of	O
+the	O
+Gus	B-GENE
+gene	I-GENE
+specifically	O
+in	O
+the	O
+endosperm	O
+during	O
+mid	O
+-	O
+development	O
+(	O
+first	O
+detected	O
+10	O
+-	O
+12	O
+d	O
+after	O
+anthesis	O
+)	O
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+native	B-GENE
+MRCK	I-GENE
+exists	O
+in	O
+high	O
+-	O
+molecular	O
+-	O
+weight	O
+complexes	O
+.	O
+
+Regression	O
+analyses	O
+showed	O
+that	O
+SOREMP	O
+dream	O
+occurrences	O
+were	O
+significantly	O
+related	O
+to	O
+the	O
+amount	O
+of	O
+REM	O
+sleep	O
+,	O
+while	O
+NREMP	O
+dream	O
+occurrences	O
+were	O
+related	O
+to	O
+arousals	O
+from	O
+NREM	O
+sleep	O
+.	O
+
+Instead	O
+,	O
+TRPS1	B-GENE
+potently	O
+and	O
+specifically	O
+represses	O
+transcriptional	O
+activation	O
+mediated	O
+by	O
+other	O
+GATA	B-GENE
+factors	I-GENE
+.	O
+
+9	O
+.	O
+7	O
+(	O
+95	O
+%	O
+CI	O
+:	O
+9	O
+.	O
+6	O
+-	O
+9	O
+.	O
+7	O
+)	O
+micromol	O
+/	O
+L	O
+among	O
+women	O
+(	O
+P	O
+=	O
+0	O
+.	O
+003	O
+)	O
+.	O
+
+Three	O
+patients	O
+received	O
+additional	O
+cycles	O
+of	O
+5	O
+-	O
+fluorouracil	O
++	O
+/	O
+-	O
+leucovorin	O
+as	O
+maintenance	O
+chemotherapy	O
+.	O
+RESULTS	O
+:	O
+Thirty	O
+males	O
+and	O
+21	O
+females	O
+with	O
+a	O
+median	O
+age	O
+of	O
+55	O
+years	O
+(	O
+range	O
+31	O
+-	O
+-	O
+73	O
+years	O
+)	O
+were	O
+treated	O
+.	O
+
+Secretion	O
+of	O
+interleukin	B-GENE
+-	I-GENE
+8	I-GENE
+,	O
+RANTES	B-GENE
+,	O
+macrophage	B-GENE
+inflammatory	I-GENE
+protein	I-GENE
+1alpha	I-GENE
+,	O
+and	O
+10	B-GENE
+-	I-GENE
+kappaDa	I-GENE
+IFN	I-GENE
+-	I-GENE
+gamma	I-GENE
+-	I-GENE
+inducible	I-GENE
+protein	I-GENE
+were	O
+increased	O
+in	O
+differentiating	O
+keratinocytes	O
+by	O
+E6	B-GENE
+.	O
+
+Another	O
+mutant	O
+,	O
+T255A	O
+,	O
+lost	O
+the	O
+ability	O
+to	O
+bind	O
+E4orf6	B-GENE
+,	O
+but	O
+unexpectedly	O
+,	O
+viral	O
+late	O
+-	O
+gene	O
+expression	O
+was	O
+not	O
+affected	O
+.	O
+
+Herein	O
+PPARgamma	B-GENE
+,	O
+liganded	O
+by	O
+either	O
+natural	O
+(	O
+15d	O
+-	O
+PGJ	O
+(	O
+2	O
+)	O
+and	O
+PGD	O
+(	O
+2	O
+)	O
+)	O
+or	O
+synthetic	O
+ligands	O
+(	O
+BRL49653	O
+and	O
+troglitazone	O
+)	O
+,	O
+selectively	O
+inhibited	O
+expression	O
+of	O
+the	O
+cyclin	B-GENE
+D1	I-GENE
+gene	I-GENE
+.	O
+
+Here	O
+we	O
+demonstrate	O
+that	O
+the	O
+Ras	B-GENE
+-	O
+activated	O
+Raf	B-GENE
+-	O
+MEK	B-GENE
+-	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+(	O
+ERK	B-GENE
+)	O
+signaling	O
+pathway	O
+can	O
+specifically	O
+control	O
+the	O
+expression	O
+of	O
+individual	O
+integrin	B-GENE
+subunits	I-GENE
+in	O
+a	O
+variety	O
+of	O
+human	O
+and	O
+mouse	O
+cell	O
+lines	O
+.	O
+
+Children	O
+who	O
+developed	O
+lower	O
+respiratory	O
+tract	O
+infections	O
+or	O
+PCP	O
+had	O
+increased	O
+rates	O
+of	O
+decline	O
+of	O
+CD4	B-GENE
+cell	O
+counts	O
+during	O
+the	O
+first	O
+6	O
+months	O
+of	O
+life	O
+.	O
+
+The	O
+reproductive	O
+effects	O
+of	O
+the	O
+administration	O
+of	O
+4	O
+-	O
+chloro	O
+-	O
+2	O
+-	O
+methylphenoxyacetic	O
+acid	O
+(	O
+MCPA	O
+)	O
+to	O
+rats	O
+were	O
+evaluated	O
+through	O
+two	O
+generations	O
+,	O
+from	O
+prior	O
+to	O
+mating	O
+,	O
+throughout	O
+mating	O
+,	O
+to	O
+gestation	O
+and	O
+lactation	O
+.	O
+
+Coexposure	O
+to	O
+FP	O
+also	O
+resulted	O
+in	O
+a	O
+more	O
+pronounced	O
+and	O
+sustained	O
+activation	O
+of	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+/	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+cascade	O
+after	O
+PMA	O
+treatment	O
+,	O
+although	O
+disruption	O
+of	O
+this	O
+pathway	O
+by	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+1	I-GENE
+inhibitor	O
+U0126	O
+did	O
+not	O
+prevent	O
+potentiation	O
+of	O
+apoptosis	O
+.	O
+
+Also	O
+,	O
+the	O
+EWS	B-GENE
+protein	I-GENE
+stimulates	O
+transcription	O
+mediated	O
+by	O
+the	O
+COOH	O
+-	O
+terminal	O
+transactivation	O
+domain	O
+of	O
+the	O
+cofactor	O
+CREB	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+CBP	B-GENE
+)	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+have	O
+determined	O
+the	O
+ICBP90	B-GENE
+gene	I-GENE
+structure	O
+by	O
+screening	O
+of	O
+a	O
+human	O
+placenta	O
+genomic	O
+library	O
+and	O
+PCR	O
+analysis	O
+.	O
+
+Tumor	O
+-	O
+like	O
+accumulation	O
+on	O
+Tl	O
+-	O
+201	O
+SPECT	O
+in	O
+subacute	O
+hemorrhagic	O
+cerebral	O
+infarction	O
+.	O
+
+METHODS	O
+:	O
+126	O
+patients	O
+with	O
+histologically	O
+confirmed	O
+MFH	O
+were	O
+analyzed	O
+.	O
+
+It	O
+is	O
+surprising	O
+that	O
+dnaE173	O
+,	O
+a	O
+potent	O
+mutator	O
+mutation	O
+specific	O
+for	O
+sequence	O
+substitution	O
+as	O
+well	O
+as	O
+single	O
+-	O
+base	O
+frameshift	O
+,	O
+did	O
+not	O
+enhance	O
+the	O
+frequency	O
+of	O
+the	O
+hot	O
+-	O
+spot	O
+frameshift	O
+mutation	O
+.	O
+
+Its	O
+transcription	O
+in	O
+vitro	O
+by	O
+pol	B-GENE
+III	I-GENE
+requires	O
+the	O
+same	O
+factors	O
+as	O
+the	O
+U6	B-GENE
+gene	I-GENE
+with	O
+the	O
+major	O
+exception	O
+that	O
+the	O
+modified	O
+TATA	O
+-	O
+box	O
+of	O
+this	O
+construct	O
+only	O
+interacts	O
+with	O
+a	O
+TATA	B-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+(	O
+TBP	B-GENE
+)	O
+mutant	O
+(	O
+TBP	B-GENE
+-	I-GENE
+DR2	I-GENE
+)	O
+but	O
+not	O
+with	O
+TBP	B-GENE
+wild	I-GENE
+-	I-GENE
+type	I-GENE
+(	O
+TBPwt	B-GENE
+)	O
+.	O
+
+HSF	B-GENE
+binds	O
+DNA	O
+as	O
+a	O
+trimer	O
+,	O
+and	O
+additional	O
+trimers	O
+can	O
+bind	O
+DNA	O
+co	O
+-	O
+operatively	O
+.	O
+
+We	O
+also	O
+demonstrate	O
+that	O
+the	O
+spo20	B-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+gene	I-GENE
+product	I-GENE
+is	O
+structurally	O
+homologous	O
+to	O
+Saccharomyces	B-GENE
+cerevisiae	I-GENE
+Sec14	I-GENE
+,	O
+the	O
+major	O
+phosphatidylinositol	O
+transfer	O
+protein	O
+of	O
+budding	O
+yeast	O
+.	O
+
+There	O
+was	O
+no	O
+evidence	O
+of	O
+linkage	O
+disequilibrium	O
+between	O
+the	O
+polymorphic	O
+site	O
+in	O
+the	O
+B	O
+cell	O
+specific	O
+promoter	O
+and	O
+those	O
+in	O
+the	O
+3	O
+'	O
+UTR	O
+.	O
+
+Their	O
+numbers	O
+have	O
+regularly	O
+increased	O
+since	O
+the	O
+mid	O
+-	O
+1970s	O
+.	O
+
+Specimen	O
+mass	O
+reduction	O
+increased	O
+with	O
+irradiance	O
+from	O
+19	O
+to	O
+72	O
+%	O
+of	O
+the	O
+initial	O
+mass	O
+for	O
+9	O
+-	O
+-	O
+31	O
+W	O
+/	O
+cm	O
+(	O
+2	O
+)	O
+,	O
+respectively	O
+.	O
+
+In	O
+conclusion	O
+,	O
+tube	O
+size	O
+estimated	O
+by	O
+Cole	O
+'	O
+s	O
+formula	O
+tends	O
+to	O
+be	O
+smaller	O
+than	O
+practically	O
+appropriate	O
+tube	O
+size	O
+for	O
+pediatric	O
+cardiac	O
+anesthesia	O
+,	O
+and	O
+therefore	O
+we	O
+suggest	O
+new	O
+formula	O
+to	O
+estimate	O
+the	O
+tube	O
+size	O
+.	O
+
+An	O
+F222W	B-GENE
+:	I-GENE
+W21F	I-GENE
+rGST	I-GENE
+A1	I-GENE
+-	I-GENE
+1	I-GENE
+double	I-GENE
+mutant	I-GENE
+provides	O
+a	O
+direct	O
+fluorescence	O
+probe	O
+of	O
+changes	O
+in	O
+the	O
+environment	O
+of	O
+the	O
+C	O
+-	O
+terminal	O
+residue	O
+.	O
+
+The	O
+recessive	O
+hos1	B-GENE
+mutation	O
+causes	O
+enhanced	O
+induction	O
+of	O
+the	O
+CBF	B-GENE
+transcription	I-GENE
+factors	I-GENE
+by	O
+low	O
+temperature	O
+as	O
+well	O
+as	O
+of	O
+their	O
+downstream	O
+cold	O
+-	O
+responsive	O
+genes	O
+.	O
+
+Stable	O
+transfection	O
+of	O
+human	B-GENE
+CHOP	I-GENE
+cDNA	I-GENE
+into	O
+mammary	O
+carcinoma	O
+cells	O
+demonstrated	O
+that	O
+CHOP	B-GENE
+functioned	O
+not	O
+as	O
+a	O
+mediator	O
+of	O
+hGH	B-GENE
+-	O
+stimulated	O
+mitogenesis	O
+but	O
+rather	O
+enhanced	O
+the	O
+protection	O
+from	O
+apoptosis	O
+afforded	O
+by	O
+hGH	B-GENE
+in	O
+a	O
+p38	B-GENE
+MAPK	O
+-	O
+dependent	O
+manner	O
+.	O
+
+A	O
+comparison	O
+of	O
+the	O
+duplicated	O
+Vkappa	B-GENE
+genes	I-GENE
+suggests	O
+positive	O
+selection	O
+on	O
+the	O
+complementarity	O
+-	O
+determining	O
+regions	O
+of	O
+the	O
+duplicated	O
+genes	O
+by	O
+point	O
+mutations	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+ubiquitous	O
+expression	O
+of	O
+p19	B-GENE
+(	O
+INK4d	B-GENE
+)	O
+has	O
+not	O
+been	O
+previously	O
+described	O
+in	O
+human	O
+or	O
+murine	O
+B	O
+-	O
+lineage	O
+cells	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+cognitive	O
+stimulation	O
+enhanced	O
+performance	O
+on	O
+the	O
+Boston	O
+Naming	O
+Test	O
+and	O
+a	O
+Word	O
+List	O
+Recognition	O
+Task	O
+;	O
+physical	O
+intervention	O
+,	O
+however	O
+,	O
+did	O
+not	O
+reach	O
+statistical	O
+significance	O
+.	O
+
+Instead	O
+,	O
+affective	O
+flattening	O
+was	O
+associated	O
+with	O
+both	O
+dopamine	B-GENE
+receptor	I-GENE
+sensitivity	O
+and	O
+psychomotor	O
+slowing	O
+.	O
+
+Homo	O
+-	O
+oligomerisation	O
+and	O
+nuclear	O
+localisation	O
+of	O
+mouse	B-GENE
+histone	I-GENE
+deacetylase	I-GENE
+1	I-GENE
+.	O
+
+With	O
+NEU	B-GENE
+overexpression	O
+,	O
+nodal	O
+control	O
+decreased	O
+from	O
+72	O
+%	O
+to	O
+34	O
+%	O
+(	O
+p	O
+=	O
+.	O
+008	O
+)	O
+.	O
+
+At	O
+the	O
+time	O
+of	O
+the	O
+blind	O
+therapeutic	O
+doses	O
+,	O
+Tg	B-GENE
+-	O
+off	O
+values	O
+ranged	O
+from	O
+8	O
+to	O
+608	O
+microg	O
+/	O
+l	O
+.	O
+
+Effects	O
+of	O
+a	O
+booster	O
+dose	O
+of	O
+tetanus	O
+toxoid	O
+after	O
+different	O
+primary	O
+courses	O
+of	O
+vaccination	O
+:	O
+implications	O
+on	O
+the	O
+use	O
+of	O
+immune	B-GENE
+globulin	I-GENE
+.	O
+
+Using	O
+RACE	O
+techniques	O
+we	O
+have	O
+cloned	O
+and	O
+sequenced	O
+one	O
+of	O
+the	O
+hamster	O
+liver	O
+3	B-GENE
+-	I-GENE
+hydroxy	I-GENE
+-	I-GENE
+hexobarbital	I-GENE
+dehydrogenases	I-GENE
+which	O
+catalyze	O
+not	O
+only	O
+cyclic	O
+alcohols	O
+but	O
+also	O
+17beta	O
+-	O
+hydroxy	O
+-	O
+steroids	O
+and	O
+3alpha	O
+-	O
+hydroxysteroids	O
+.	O
+
+An	O
+association	O
+was	O
+demonstrated	O
+between	O
+the	O
+expression	O
+of	O
+aberrantly	O
+and	O
+/	O
+or	O
+alternatively	O
+spliced	O
+mdm2	B-GENE
+mRNAs	I-GENE
+and	O
+a	O
+lack	O
+of	O
+progesterone	B-GENE
+receptor	I-GENE
+.	O
+
+Histological	O
+examination	O
+showed	O
+lichenoid	O
+changes	O
+,	O
+acantholytic	O
+blister	O
+formation	O
+and	O
+apoptotic	O
+keratinocytes	O
+.	O
+
+We	O
+find	O
+that	O
+our	O
+response	O
+function	O
+is	O
+well	O
+approximated	O
+by	O
+the	O
+GSER	O
+only	O
+within	O
+a	O
+particular	O
+frequency	O
+range	O
+determined	O
+by	O
+the	O
+material	O
+parameters	O
+of	O
+both	O
+the	O
+bead	O
+and	O
+the	O
+network	O
+.	O
+
+It	O
+is	O
+shown	O
+that	O
+,	O
+for	O
+any	O
+periodic	O
+input	O
+,	O
+the	O
+map	O
+representing	O
+the	O
+relation	O
+between	O
+input	O
+phases	O
+at	O
+consecutive	O
+discharge	O
+times	O
+can	O
+be	O
+restricted	O
+to	O
+a	O
+piecewise	O
+continuous	O
+,	O
+orientation	O
+preserving	O
+circle	O
+map	O
+.	O
+
+Nine	O
+strains	O
+were	O
+subtyped	O
+as	O
+Camp	O
+.	O
+jejuni	O
+subsp	O
+.	O
+jejuni	O
+biotype	O
+II	O
+and	O
+the	O
+remaining	O
+ones	O
+as	O
+biotype	O
+I	O
+.	O
+
+Analysis	O
+of	O
+mCTR	B-GENE
+mRNAs	I-GENE
+has	O
+revealed	O
+that	O
+the	O
+three	O
+alternative	O
+promoters	O
+give	O
+rise	O
+to	O
+at	O
+least	O
+seven	O
+mCTR	B-GENE
+isoforms	I-GENE
+in	O
+the	O
+5	O
+'	O
+region	O
+of	O
+the	O
+gene	O
+and	O
+generate	O
+5	O
+'	O
+-	O
+untranslated	O
+regions	O
+of	O
+very	O
+different	O
+lengths	O
+.	O
+
+Effects	O
+of	O
+3	O
+'	O
+terminus	O
+modifications	O
+on	O
+mRNA	O
+functional	O
+decay	O
+during	O
+in	O
+vitro	O
+protein	O
+synthesis	O
+.	O
+
+A	O
+comprehensive	O
+neuropsychological	O
+battery	O
+was	O
+administered	O
+to	O
+48	O
+veterans	O
+with	O
+Gulf	O
+War	O
+Illness	O
+(	O
+GWI	O
+)	O
+characterized	O
+by	O
+severe	O
+fatigue	O
+(	O
+GV	O
+-	O
+F	O
+)	O
+and	O
+39	O
+healthy	O
+veterans	O
+(	O
+GV	O
+-	O
+H	O
+)	O
+.	O
+
+Reverse	O
+transcription	O
+-	O
+PCR	O
+analysis	O
+of	O
+mRNA	O
+from	O
+patients	O
+shows	O
+that	O
+each	O
+of	O
+these	O
+five	O
+mutations	O
+results	O
+in	O
+aberrant	O
+splicing	O
+.	O
+
+RESULTS	O
+:	O
+Coronary	O
+mortality	O
+during	O
+the	O
+median	O
+follow	O
+-	O
+up	O
+time	O
+of	O
+17	O
+months	O
+was	O
+6	O
+-	O
+fold	O
+higher	O
+in	O
+the	O
+highest	O
+tertile	O
+for	O
+CRP	B-GENE
+and	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+and	O
+3	O
+.	O
+5	O
+-	O
+fold	O
+higher	O
+in	O
+the	O
+highest	O
+tertile	O
+for	O
+fibrinogen	B-GENE
+and	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+than	O
+in	O
+the	O
+respective	O
+combined	O
+lower	O
+tertiles	O
+.	O
+
+The	O
+relationship	O
+of	O
+the	O
+factor	B-GENE
+V	I-GENE
+Leiden	I-GENE
+mutation	I-GENE
+or	O
+the	O
+deletion	O
+-	O
+deletion	O
+polymorphism	O
+of	O
+the	O
+angiotensin	B-GENE
+converting	I-GENE
+enzyme	I-GENE
+to	O
+postoperative	O
+thromboembolic	O
+events	O
+following	O
+total	O
+joint	O
+arthroplasty	O
+.	O
+
+To	O
+examine	O
+transcriptional	O
+regulation	O
+of	O
+the	O
+rat	B-GENE
+eIF4E	I-GENE
+gene	I-GENE
+,	O
+2	O
+.	O
+1	O
+kB	O
+of	O
+the	O
+rat	B-GENE
+eIF4E	I-GENE
+promoter	I-GENE
+region	I-GENE
+was	O
+cloned	O
+and	O
+the	O
+contribution	O
+of	O
+specific	O
+elements	O
+in	O
+regulating	O
+transcription	O
+was	O
+determined	O
+in	O
+primary	O
+cultures	O
+of	O
+rat	O
+cardiocytes	O
+and	O
+in	O
+a	O
+murine	O
+C	O
+(	O
+2	O
+)	O
+C	O
+(	O
+12	O
+)	O
+myoblast	O
+cell	O
+line	O
+.	O
+
+In	O
+the	O
+remaining	O
+case	O
+,	O
+the	O
+aneurysm	O
+originated	O
+from	O
+the	O
+proximal	O
+end	O
+of	O
+the	O
+associated	O
+A1	O
+fenestration	O
+.	O
+
+GABA	B-GENE
+(	I-GENE
+B	I-GENE
+)	I-GENE
+R1g	I-GENE
+was	O
+expressed	O
+in	O
+both	O
+brain	O
+and	O
+peripheral	O
+tissues	O
+.	O
+
+Raes	O
+,	O
+P	O
+.	O
+
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+pathway	O
+activation	O
+occurs	O
+during	O
+transformation	O
+induced	O
+by	O
+a	O
+number	O
+of	O
+classical	O
+oncogenes	O
+,	O
+including	O
+Bcr	B-GENE
+/	O
+Abl	B-GENE
+,	O
+Ras	B-GENE
+and	O
+Rac	B-GENE
+,	O
+and	O
+is	O
+necessary	O
+for	O
+full	O
+transforming	O
+potential	O
+.	O
+
+We	O
+used	O
+a	O
+rev	B-GENE
+-	O
+and	O
+RRE	B-GENE
+-	O
+defective	O
+HIV	O
+type	O
+1	O
+(	O
+HIV	O
+-	O
+1	O
+)	O
+molecular	O
+clone	O
+in	O
+complementation	O
+experiments	O
+to	O
+establish	O
+a	O
+method	O
+for	O
+the	O
+rapid	O
+isolation	O
+of	O
+posttranscriptional	O
+regulatory	O
+elements	O
+from	O
+the	O
+mammalian	O
+genome	O
+by	O
+selecting	O
+for	O
+rescue	O
+of	O
+virus	O
+replication	O
+.	O
+
+Copyright	O
+2001	O
+Academic	O
+Press	O
+.	O
+
+A	O
+novel	O
+myeloid	O
+-	O
+restricted	O
+zebrafish	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+-	I-GENE
+binding	I-GENE
+protein	I-GENE
+with	O
+a	O
+potent	O
+transcriptional	O
+activation	O
+domain	O
+.	O
+
+Recently	O
+,	O
+we	O
+discovered	O
+that	O
+alanine	O
+substitutions	O
+of	O
+the	O
+active	O
+center	O
+cleft	O
+residues	O
+significantly	O
+impair	O
+the	O
+depurinating	O
+and	O
+ribosome	O
+inhibitory	O
+activity	O
+of	O
+PAP	B-GENE
+.	O
+
+SH2D1A	B-GENE
+protein	I-GENE
+levels	O
+are	O
+up	O
+-	O
+regulated	O
+by	O
+CD40	B-GENE
+cross	O
+-	O
+linking	O
+and	O
+down	O
+-	O
+regulated	O
+by	O
+B	B-GENE
+cell	I-GENE
+receptor	I-GENE
+ligation	O
+.	O
+
+Cross	O
+-	O
+linking	O
+FcalphaR	B-GENE
+on	O
+wt	B-GENE
+-	I-GENE
+ITAM	I-GENE
+or	O
+IIA	B-GENE
+-	I-GENE
+ITAM	I-GENE
+cells	O
+triggered	O
+equivalent	O
+PI	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+-	O
+dependent	O
+activation	O
+of	O
+PKBalpha	B-GENE
+.	O
+
+RPM	B-GENE
+/	O
+RGL3	B-GENE
+resembled	O
+AF	B-GENE
+-	I-GENE
+6	I-GENE
+and	O
+Nore1	B-GENE
+in	O
+interacting	O
+strongly	O
+with	O
+constitutively	O
+active	O
+M	B-GENE
+-	I-GENE
+Ras	I-GENE
+and	O
+p21	B-GENE
+Ras	I-GENE
+.	O
+
+A	O
+novel	O
+potential	O
+effector	O
+of	O
+M	B-GENE
+-	I-GENE
+Ras	I-GENE
+and	O
+p21	B-GENE
+Ras	I-GENE
+negatively	O
+regulates	O
+p21	B-GENE
+Ras	I-GENE
+-	O
+mediated	O
+gene	O
+induction	O
+and	O
+cell	O
+growth	O
+.	O
+
+The	O
+mice	O
+are	O
+phenotypically	O
+normal	O
+and	O
+do	O
+not	O
+develop	O
+spontaneous	O
+tumors	O
+at	O
+an	O
+early	O
+age	O
+,	O
+in	O
+contrast	O
+to	O
+knock	O
+-	O
+out	O
+(	O
+p53	B-GENE
+(	I-GENE
+-	I-GENE
+/	I-GENE
+-	I-GENE
+)	I-GENE
+)	O
+strains	O
+with	O
+a	O
+defective	O
+p53	B-GENE
+gene	I-GENE
+.	O
+
+Cyclins	B-GENE
+are	O
+one	O
+of	O
+the	O
+pivotal	O
+determinants	O
+regulating	O
+cell	O
+cycle	O
+progression	O
+.	O
+
+Evidence	O
+-	O
+based	O
+care	O
+:	O
+a	O
+new	O
+formula	O
+for	O
+an	O
+old	O
+problem	O
+?	O
+
+Further	O
+,	O
+the	O
+osteo	O
+-	O
+retentive	O
+ability	O
+of	O
+the	O
+hydroxyapatite	O
+in	O
+the	O
+sockets	O
+was	O
+seen	O
+to	O
+be	O
+close	O
+to	O
+significance	O
+(	O
+after	O
+six	O
+months	O
+width	O
+differences	O
+,	O
+in	O
+the	O
+canine	O
+region	O
+:	O
+P	O
+=	O
+0	O
+.	O
+059	O
+,	O
+LHS	O
+,	O
+and	O
+P	O
+=	O
+0	O
+.	O
+065	O
+,	O
+RHS	O
+)	O
+.	O
+
+The	O
+cleavage	O
+site	O
+between	O
+VPg	B-GENE
+and	O
+RNA	B-GENE
+dependent	I-GENE
+RNA	I-GENE
+polymerase	I-GENE
+was	O
+predicted	O
+to	O
+be	O
+E445	O
+-	O
+T446	O
+based	O
+on	O
+the	O
+amino	O
+acid	O
+sequence	O
+analysis	O
+of	O
+the	O
+polyprotein	O
+from	O
+different	O
+sobemoviruses	O
+.	O
+
+The	O
+%	O
+SVend	O
+of	O
+HCM	O
+-	O
+I	O
+was	O
+significantly	O
+lower	O
+than	O
+the	O
+respective	O
+values	O
+of	O
+the	O
+HCM	O
+-	O
+II	O
+and	O
+Control	O
+groups	O
+.	O
+
+Nearly	O
+all	O
+isolates	O
+of	O
+S	O
+.	O
+intermedius	O
+and	O
+most	O
+isolates	O
+of	O
+S	O
+.	O
+constellatus	O
+,	O
+but	O
+only	O
+19	O
+%	O
+of	O
+those	O
+of	O
+S	O
+.	O
+anginosus	O
+,	O
+were	O
+associated	O
+with	O
+abscess	O
+.	O
+
+DESIGN	O
+:	O
+Retrospective	O
+study	O
+.	O
+
+Human	O
+brain	O
+cDNA	O
+library	O
+screening	O
+and	O
+5	O
+'	O
+rapid	O
+amplification	O
+of	O
+cDNA	O
+ends	O
+yielded	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+DENTT	I-GENE
+cDNA	I-GENE
+containing	O
+an	O
+1899	O
+-	O
+bp	O
+open	O
+reading	O
+frame	O
+encoding	O
+a	O
+predicted	O
+633	O
+-	O
+amino	O
+-	O
+acid	O
+protein	O
+with	O
+four	O
+potential	O
+nuclear	O
+localization	O
+signals	O
+(	O
+NLSs	O
+)	O
+and	O
+two	O
+coiled	O
+-	O
+coil	O
+regions	O
+.	O
+
+Transfection	O
+of	O
+EGFP	B-GENE
+-	O
+tagged	O
+DENTT	B-GENE
+NLS	O
+deletion	O
+constructs	O
+lacking	O
+the	O
+bipartite	O
+NLS	B-GENE
+-	I-GENE
+1	I-GENE
+were	O
+excluded	O
+from	O
+the	O
+nucleolus	O
+.	O
+
+These	O
+genes	O
+encode	O
+a	O
+tryptophanyl	B-GENE
+tRNA	I-GENE
+,	O
+the	O
+protein	B-GENE
+translocase	I-GENE
+component	O
+SecE	B-GENE
+,	O
+the	O
+antiterminator	B-GENE
+protein	I-GENE
+NusG	I-GENE
+,	O
+and	O
+the	O
+ribosomal	O
+proteins	O
+L11	B-GENE
+and	O
+L1	B-GENE
+in	O
+addition	O
+to	O
+PkwR	B-GENE
+,	O
+a	O
+putative	O
+regulatory	O
+protein	O
+of	O
+the	O
+LacI	B-GENE
+-	O
+GalR	B-GENE
+family	O
+.	O
+
+Rapamycin	O
+(	O
+FRAP	B-GENE
+/	O
+mTOR	B-GENE
+inhibitor	O
+)	O
+blocked	O
+4E	B-GENE
+-	I-GENE
+BP1	I-GENE
+phosphorylation	O
+causing	O
+a	O
+predominance	O
+of	O
+the	O
+alpha	O
+(	O
+hypophosphorylated	O
+)	O
+band	O
+.	O
+
+Sixteen	O
+out	O
+of	O
+52	O
+seropositive	O
+MS	O
+patients	O
+(	O
+30	O
+.	O
+8	O
+%	O
+)	O
+showed	O
+intrathecal	O
+synthesis	O
+of	O
+C	B-GENE
+.	I-GENE
+pneumoniae	I-GENE
+-	I-GENE
+specific	I-GENE
+IgG	I-GENE
+but	O
+only	O
+one	O
+of	O
+43	O
+seropositive	O
+controls	O
+(	O
+2	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+Far	O
+Western	O
+blot	O
+analysis	O
+suggested	O
+that	O
+the	O
+tandem	O
+SH2	B-GENE
+domains	I-GENE
+of	O
+SHP2	B-GENE
+bind	O
+to	O
+Gab1	B-GENE
+in	O
+a	O
+specific	O
+orientation	O
+,	O
+in	O
+which	O
+the	O
+N	B-GENE
+-	I-GENE
+SH2	I-GENE
+domain	I-GENE
+binds	O
+to	O
+phosphotyrosine	O
+(	O
+Tyr	O
+(	O
+P	O
+)	O
+)	O
+-	O
+627	O
+and	O
+the	O
+C	B-GENE
+-	I-GENE
+SH2	I-GENE
+domain	I-GENE
+binds	O
+to	O
+Tyr	O
+(	O
+P	O
+)	O
+-	O
+659	O
+.	O
+
+Molecular	O
+cloning	O
+,	O
+genomic	O
+mapping	O
+,	O
+and	O
+expression	O
+of	O
+two	O
+secretor	B-GENE
+blood	I-GENE
+group	I-GENE
+alpha	I-GENE
+(	I-GENE
+1	I-GENE
+,	I-GENE
+2	I-GENE
+)	I-GENE
+fucosyltransferase	I-GENE
+genes	I-GENE
+differentially	O
+regulated	O
+in	O
+mouse	O
+uterine	O
+epithelium	O
+and	O
+gastrointestinal	O
+tract	O
+.	O
+
+The	O
+UBA	B-GENE
+domains	I-GENE
+of	O
+RAD23	B-GENE
+and	O
+DDI1	B-GENE
+are	O
+required	O
+for	O
+these	O
+interactions	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+intrathecal	O
+administration	O
+(	O
+i	O
+.	O
+t	O
+.	O
+)	O
+of	O
+D2	B-GENE
+receptor	I-GENE
+agonist	O
+LY171555	O
+or	O
+D1	B-GENE
+/	I-GENE
+D2	I-GENE
+receptor	I-GENE
+agonist	O
+apomorphine	O
+increased	O
+pain	O
+threshold	O
+and	O
+had	O
+a	O
+potentiating	O
+effect	O
+on	O
+AA	O
+.	O
+
+The	O
+R2	O
+between	O
+MFI	O
+of	O
+fresh	O
+and	O
+frozen	O
+muscle	O
+was	O
+0	O
+.	O
+94	O
+and	O
+0	O
+.	O
+92	O
+for	O
+lamb	O
+and	O
+pork	O
+longissimus	O
+,	O
+respectively	O
+.	O
+
+After	O
+all	O
+doses	O
+of	O
+d	O
+-	O
+amphetamine	O
+,	O
+responding	O
+occurred	O
+largely	O
+on	O
+the	O
+saline	O
+key	O
+under	O
+both	O
+schedules	O
+.	O
+
+Intravenous	O
+L	O
+-	O
+carnitine	O
+treatment	O
+increased	O
+plasma	O
+carnitine	O
+concentrations	O
+,	O
+improved	O
+patient	O
+-	O
+assessed	O
+fatigue	O
+,	O
+and	O
+may	O
+prevent	O
+the	O
+decline	O
+in	O
+peak	O
+exercise	O
+capacity	O
+in	O
+hemodialysis	O
+patients	O
+.	O
+
+Elevated	O
+expression	O
+of	O
+full	B-GENE
+-	I-GENE
+length	I-GENE
+UhpB	I-GENE
+or	O
+of	O
+a	O
+soluble	O
+hybrid	O
+protein	O
+,	O
+GST	B-GENE
+-	O
+Bc	B-GENE
+,	O
+which	O
+is	O
+glutathione	B-GENE
+S	I-GENE
+-	I-GENE
+transferase	I-GENE
+(	O
+GST	B-GENE
+)	O
+fused	O
+to	O
+the	O
+cytoplasmic	O
+C	O
+-	O
+terminal	O
+portion	O
+of	O
+UhpB	B-GENE
+,	O
+results	O
+in	O
+complete	O
+blockage	O
+of	O
+uhpT	B-GENE
+expression	O
+in	O
+a	O
+uhp	B-GENE
+(	I-GENE
++	I-GENE
+)	I-GENE
+strain	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+PKC	B-GENE
+and	O
+p44	B-GENE
+/	O
+p42MAPK	B-GENE
+signalings	O
+are	O
+required	O
+for	O
+the	O
+HBx	B-GENE
+-	O
+induced	O
+Sp1	B-GENE
+-	O
+mediated	O
+IGF	B-GENE
+-	I-GENE
+II	I-GENE
+P4	I-GENE
+transcriptional	O
+activity	O
+since	O
+(	O
+i	O
+)	O
+PKC	B-GENE
+activation	O
+by	O
+PMA	O
+or	O
+PKC	B-GENE
+expression	O
+vector	O
+increases	O
+Sp1	B-GENE
+phosphorylation	O
+and	O
+P4	B-GENE
+activity	O
+in	O
+HBx	B-GENE
+-	O
+transfected	O
+HepG2	O
+cells	O
+;	O
+(	O
+ii	O
+)	O
+PKC	B-GENE
+inhibition	O
+by	O
+PKC	B-GENE
+inhibitor	O
+Go6976	O
+reduces	O
+Sp1	B-GENE
+phosphorylation	O
+,	O
+P4	B-GENE
+activity	O
+,	O
+and	O
+IGF	B-GENE
+-	I-GENE
+II	I-GENE
+mRNA	I-GENE
+in	O
+HBx	B-GENE
+-	O
+transfected	O
+HepG2	O
+cells	O
+;	O
+and	O
+(	O
+iii	O
+)	O
+the	O
+inhibition	O
+of	O
+MEK	B-GENE
+activation	O
+by	O
+U0126	O
+reduces	O
+Sp1	B-GENE
+phosphorylation	O
+,	O
+P4	B-GENE
+activity	O
+and	O
+IGF	B-GENE
+-	I-GENE
+II	I-GENE
+mRNA	I-GENE
+in	O
+HBx	B-GENE
+-	O
+transfected	O
+HepG2	O
+cells	O
+.	O
+
+Through	O
+two	O
+novel	O
+mechanisms	O
+,	O
+Arf	B-GENE
+inhibits	O
+the	O
+oncoprotein	B-GENE
+Hdm2	I-GENE
+,	O
+a	O
+negative	O
+regulator	O
+of	O
+p53	B-GENE
+.	O
+
+In	O
+the	O
+free	O
+-	O
+swimming	O
+rotatory	O
+test	O
+mice	O
+spend	O
+most	O
+of	O
+the	O
+time	O
+swimming	O
+close	O
+to	O
+the	O
+wall	O
+of	O
+the	O
+container	O
+attempting	O
+to	O
+escape	O
+from	O
+an	O
+aversive	O
+test	O
+situation	O
+.	O
+
+Examination	O
+of	O
+various	O
+promoter	O
+deletion	O
+mutants	O
+indicated	O
+that	O
+SF	B-GENE
+-	I-GENE
+1	I-GENE
+acts	O
+through	O
+the	O
+proximal	O
+promoter	O
+region	O
+and	O
+upstream	O
+promoter	O
+sequences	O
+.	O
+
+Prrp	B-GENE
+can	O
+also	O
+associate	O
+with	O
+the	O
+EVH1	B-GENE
+domain	I-GENE
+of	O
+Mena	B-GENE
+,	O
+another	O
+microfilament	O
+-	O
+associated	O
+protein	O
+.	O
+
+Srb10	B-GENE
+is	O
+a	O
+physiological	O
+regulator	O
+of	O
+Gcn4	B-GENE
+stability	O
+because	O
+both	O
+phosphorylation	O
+and	O
+turnover	O
+of	O
+Gcn4	B-GENE
+are	O
+diminished	O
+in	O
+srb10	B-GENE
+mutants	I-GENE
+.	O
+
+A	O
+new	O
+intron	O
+of	O
+476	O
+base	O
+pairs	O
+was	O
+found	O
+in	O
+the	O
+middle	O
+of	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+leader	O
+sequence	O
+and	O
+was	O
+shown	O
+to	O
+robustly	O
+enhance	O
+the	O
+promoter	O
+activity	O
+.	O
+
+Based	O
+on	O
+this	O
+analysis	O
+,	O
+we	O
+propose	O
+that	O
+the	O
+interactions	O
+of	O
+Sos	B-GENE
+with	O
+the	O
+switch	O
+1	O
+and	O
+switch	O
+2	O
+regions	O
+of	O
+Ras	B-GENE
+have	O
+distinct	O
+functional	O
+consequences	O
+:	O
+the	O
+interaction	O
+with	O
+switch	O
+2	O
+mediates	O
+the	O
+anchoring	O
+of	O
+Ras	B-GENE
+to	O
+Sos	B-GENE
+,	O
+whereas	O
+the	O
+interaction	O
+with	O
+switch	O
+1	O
+leads	O
+to	O
+disruption	O
+of	O
+the	O
+nucleotide	O
+-	O
+binding	O
+site	O
+and	O
+GDP	O
+dissociation	O
+.	O
+
+A	O
+log	O
+-	O
+linear	O
+dose	O
+-	O
+response	O
+was	O
+obtained	O
+for	O
+the	O
+average	O
+increase	O
+in	O
+FEV1	O
+up	O
+to	O
+6	O
+h	O
+(	O
+AUC0	O
+-	O
+6	O
+h	O
+)	O
+and	O
+peak	O
+FEV1	O
+across	O
+the	O
+dose	O
+range	O
+administered	O
+by	O
+Respimat	O
+.	O
+
+Bandshift	O
+experiments	O
+demonstrate	O
+that	O
+BmHR3A	B-GENE
+binds	O
+specifically	O
+to	O
+RORE	B-GENE
+(	O
+Retinoic	B-GENE
+acid	I-GENE
+-	I-GENE
+related	I-GENE
+Orphan	I-GENE
+receptor	I-GENE
+Response	I-GENE
+Element	I-GENE
+)	O
+-	O
+like	O
+sequences	O
+in	O
+the	O
+promoters	O
+of	O
+both	O
+genes	O
+,	O
+thus	O
+suggesting	O
+a	O
+direct	O
+role	O
+for	O
+BmHR3A	B-GENE
+in	O
+regulating	O
+the	O
+expression	O
+of	O
+BmGATAbeta	B-GENE
+and	O
+ESP	B-GENE
+genes	I-GENE
+during	O
+vitellogenesis	O
+.	O
+
+This	O
+was	O
+most	O
+pronounced	O
+during	O
+the	O
+initial	O
+phase	O
+of	O
+Erk	B-GENE
+activation	O
+.	O
+
+The	O
+iterative	O
+method	O
+proposed	O
+by	O
+Bengtsson	O
+[	O
+Appl	O
+.	O
+
+The	O
+COD	O
+and	O
+color	O
+removals	O
+were	O
+both	O
+more	O
+than	O
+90	O
+%	O
+when	O
+FeCl3	O
+was	O
+used	O
+as	O
+the	O
+coagulation	O
+(	O
+dosages	O
+of	O
+two	O
+-	O
+step	O
+coagulation	O
+were	O
+0	O
+.	O
+031	O
+and	O
+0	O
+.	O
+012	O
+mol	O
+/	O
+L	O
+respectively	O
+)	O
+after	O
+a	O
+ferrous	O
+hydrogen	O
+peroxide	O
+oxidation	O
+pretreatment	O
+at	O
+a	O
+H2O2	O
+dosage	O
+of	O
+0	O
+.	O
+06	O
+mol	O
+/	O
+L	O
+.	O
+
+Although	O
+there	O
+was	O
+a	O
+high	O
+correlation	O
+between	O
+sap	O
+flux	O
+densities	O
+registered	O
+by	O
+the	O
+old	O
+and	O
+new	O
+sensors	O
+,	O
+significant	O
+differences	O
+in	O
+sap	O
+flux	O
+densities	O
+between	O
+the	O
+duplicated	O
+sensors	O
+were	O
+detected	O
+.	O
+
+Three	O
+of	O
+the	O
+proteins	O
+involved	O
+in	O
+checkpoint	O
+signaling	O
+,	O
+Rad1	B-GENE
+,	O
+Hus1	B-GENE
+,	O
+and	O
+Rad9	B-GENE
+,	O
+have	O
+been	O
+shown	O
+to	O
+interact	O
+by	O
+immunoprecipitation	O
+and	O
+yeast	O
+two	O
+-	O
+hybrid	O
+studies	O
+.	O
+
+Based	O
+on	O
+the	O
+hypothesis	O
+that	O
+evolutionarily	O
+conserved	O
+regions	O
+are	O
+functionally	O
+important	O
+and	O
+likely	O
+to	O
+interact	O
+with	O
+coactivators	O
+,	O
+we	O
+compared	O
+the	O
+amino	O
+acid	O
+sequence	O
+of	O
+C	B-GENE
+/	I-GENE
+EBPalpha	I-GENE
+from	O
+different	O
+species	O
+(	O
+frog	O
+to	O
+human	O
+)	O
+and	O
+identified	O
+four	O
+highly	O
+conserved	O
+regions	O
+(	O
+CR1	O
+-	O
+CR4	O
+)	O
+within	O
+the	O
+transactivation	O
+domain	O
+.	O
+
+Tolerance	O
+to	O
+ADAL	O
+-	O
+2	O
+was	O
+similar	O
+to	O
+that	O
+of	O
+Vicryl	O
+suture	O
+and	O
+tolerance	O
+to	O
+ADAL	O
+-	O
+2	O
+was	O
+superior	O
+to	O
+that	O
+to	O
+Tisuacryl	O
+.	O
+
+Of	O
+the	O
+patients	O
+in	O
+each	O
+regimen	O
+who	O
+reached	O
+study	O
+end	O
+points	O
+,	O
+17	O
+of	O
+29	O
+(	O
+59	O
+%	O
+)	O
+were	O
+in	O
+regimen	O
+A	O
+,	O
+11	O
+of	O
+20	O
+(	O
+55	O
+%	O
+)	O
+were	O
+in	O
+regimen	O
+B	O
+,	O
+and	O
+28	O
+of	O
+43	O
+(	O
+65	O
+%	O
+)	O
+were	O
+in	O
+regimen	O
+C	O
+met	O
+the	O
+treatment	O
+success	O
+criterion	O
+.	O
+
+SAMPLE	O
+POPULATION	O
+:	O
+MCB	O
+from	O
+7	O
+racing	O
+Greyhounds	O
+euthanatized	O
+for	O
+reasons	O
+unrelated	O
+to	O
+MCB	O
+abnormalities	O
+.	O
+
+CONCLUSIONS	O
+AND	O
+CLINICAL	O
+RELEVANCE	O
+:	O
+Increased	O
+cortical	O
+thickness	O
+and	O
+geometric	O
+properties	O
+of	O
+left	O
+MCB	O
+-	O
+IV	O
+and	O
+-	O
+V	O
+of	O
+Greyhounds	O
+,	O
+together	O
+with	O
+altered	O
+turnover	O
+and	O
+orientation	O
+of	O
+osteons	O
+in	O
+the	O
+dorsal	O
+quadrants	O
+of	O
+left	O
+MCB	O
+,	O
+are	O
+site	O
+-	O
+specific	O
+adaptive	O
+responses	O
+associated	O
+with	O
+asymmetric	O
+cyclic	O
+loading	O
+as	O
+a	O
+result	O
+of	O
+racing	O
+on	O
+circular	O
+tracks	O
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+Palmaz	O
+-	O
+Schatz	O
+stents	O
+were	O
+dip	O
+-	O
+coated	O
+with	O
+paclitaxel	O
+(	O
+0	O
+,	O
+0	O
+.	O
+2	O
+,	O
+15	O
+,	O
+or	O
+187	O
+microgram	O
+/	O
+stent	O
+)	O
+by	O
+immersion	O
+in	O
+ethanolic	O
+paclitaxel	O
+and	O
+evaporation	O
+of	O
+the	O
+solvent	O
+.	O
+
+Percentages	O
+of	O
+recovery	O
+for	O
+overload	O
+and	O
+dilution	O
+tests	O
+were	O
+between	O
+87	O
+and	O
+120	O
+%	O
+.	O
+
+One	O
+of	O
+the	O
+conserved	O
+RNA	O
+subdomains	O
+,	O
+designated	O
+P3	B-GENE
+,	O
+has	O
+previously	O
+been	O
+shown	O
+to	O
+be	O
+required	O
+for	O
+nucleolar	O
+localization	O
+.	O
+
+In	O
+Cd	O
+-	O
+spiked	O
+OECD	O
+soil	O
+,	O
+internal	O
+Cd	O
+levels	O
+were	O
+linearly	O
+related	O
+to	O
+external	O
+Cd	O
+concentrations	O
+,	O
+whereas	O
+the	O
+springtails	O
+maintained	O
+fixed	O
+internal	O
+levels	O
+of	O
+Cu	O
+and	O
+Zn	O
+regardless	O
+of	O
+spiked	O
+concentrations	O
+.	O
+
+Nutritional	O
+status	O
+in	O
+adults	O
+on	O
+an	O
+alternative	O
+or	O
+traditional	O
+diet	O
+]	O
+BACKGROUND	O
+:	O
+Plant	O
+food	O
+lacks	O
+vitamin	O
+B12	O
+,	O
+vitamin	O
+D	O
+and	O
+higher	O
+n	O
+-	O
+3	O
+polyunsaturated	O
+fatty	O
+acids	O
+.	O
+
+It	O
+is	O
+useful	O
+as	O
+an	O
+adjunct	O
+to	O
+mammography	O
+in	O
+those	O
+patients	O
+with	O
+radiographically	O
+dense	O
+breasts	O
+for	O
+the	O
+characterization	O
+of	O
+palpable	O
+masses	O
+.	O
+
+Measurements	O
+were	O
+obtained	O
+:	O
+(	O
+i	O
+)	O
+just	O
+after	O
+the	O
+traumatic	O
+exposure	O
+(	O
+D0	O
+)	O
+;	O
+(	O
+ii	O
+)	O
+3	O
+days	O
+after	O
+this	O
+first	O
+measurement	O
+(	O
+D3	O
+)	O
+;	O
+and	O
+(	O
+iii	O
+)	O
+30	O
+days	O
+after	O
+(	O
+D30	O
+)	O
+.	O
+
+Changes	O
+of	O
+the	O
+DB	O
+sequence	O
+without	O
+affecting	O
+the	O
+postulated	O
+stem	O
+structure	O
+led	O
+to	O
+drastic	O
+losses	O
+of	O
+translation	O
+efficiency	O
+.	O
+
+It	O
+has	O
+been	O
+suggested	O
+that	O
+members	O
+of	O
+this	O
+protein	O
+family	O
+exhibit	O
+both	O
+prolyl	B-GENE
+isomerase	I-GENE
+and	O
+chaperone	O
+activity	O
+.	O
+
+Inhibition	O
+of	O
+the	O
+Raf	B-GENE
+-	I-GENE
+1	I-GENE
+target	I-GENE
+ERK	B-GENE
+kinase	I-GENE
+(	O
+MEK	B-GENE
+)	O
+either	O
+attenuated	O
+or	O
+abolished	O
+Rp	O
+-	O
+cAMPS	O
+-	O
+and	O
+PKI	B-GENE
+-	O
+induced	O
+ERK	B-GENE
+activation	O
+,	O
+caldesmon	B-GENE
+phosphorylation	O
+,	O
+and	O
+stress	O
+fiber	O
+formation	O
+.	O
+
+PACAP	B-GENE
+mRNA	I-GENE
+was	O
+widely	O
+expressed	O
+in	O
+most	O
+human	O
+tissues	O
+;	O
+in	O
+transfected	O
+cells	O
+,	O
+PACAP	B-GENE
+was	O
+diffusely	O
+expressed	O
+in	O
+the	O
+cytoplasm	O
+.	O
+
+The	O
+radial	O
+forearm	O
+flap	O
+is	O
+used	O
+most	O
+commonly	O
+,	O
+however	O
+the	O
+lateral	O
+arm	O
+flap	O
+may	O
+be	O
+the	O
+flap	O
+of	O
+choice	O
+in	O
+certain	O
+situations	O
+.	O
+
+By	O
+comparison	O
+,	O
+in	O
+nontumorigenic	O
+Ad5	O
+cells	O
+,	O
+class	O
+I	O
+expression	O
+is	O
+high	O
+due	O
+to	O
+negligible	O
+binding	O
+of	O
+COUP	B-GENE
+-	I-GENE
+TF	I-GENE
+and	O
+strong	O
+binding	O
+of	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+.	O
+
+As	O
+an	O
+application	O
+of	O
+reverse	O
+genetics	O
+,	O
+we	O
+introduced	O
+one	O
+nucleotide	O
+change	O
+(	O
+UCU	O
+to	O
+ACU	O
+)	O
+to	O
+immediate	O
+downstream	O
+of	O
+the	O
+RNA	O
+-	O
+editing	O
+site	O
+of	O
+the	O
+V	B-GENE
+gene	I-GENE
+in	O
+the	O
+full	O
+-	O
+length	O
+hPIV2	O
+cDNA	O
+and	O
+were	O
+able	O
+to	O
+obtain	O
+infectious	O
+viruses	O
+[	O
+rPIV2V	O
+(	O
+-	O
+)	O
+]	O
+from	O
+the	O
+cDNA	O
+.	O
+
+The	O
+frameshift	O
+initiated	O
+by	O
+ADEx2	O
+is	O
+believed	O
+to	O
+alter	O
+the	O
+regular	O
+coding	O
+sequence	O
+,	O
+acting	O
+as	O
+a	O
+loss	O
+-	O
+of	O
+-	O
+function	O
+ASIP	B-GENE
+mutation	I-GENE
+.	O
+
+In	O
+regards	O
+to	O
+the	O
+latter	O
+activity	O
+,	O
+it	O
+has	O
+been	O
+shown	O
+that	O
+S3	B-GENE
+contains	O
+vigorous	O
+N	B-GENE
+-	I-GENE
+glycosylase	I-GENE
+activity	O
+for	O
+the	O
+removal	O
+of	O
+8	O
+-	O
+oxoguanine	O
+residues	O
+in	O
+DNA	O
+that	O
+leaves	O
+baseless	O
+sites	O
+in	O
+their	O
+places	O
+.	O
+
+Here	O
+we	O
+report	O
+the	O
+isolation	O
+and	O
+characterization	O
+of	O
+the	O
+forkhead	B-GENE
+homologue	I-GENE
+in	I-GENE
+rhabdomyosarcoma	I-GENE
+(	O
+FKHR	B-GENE
+)	O
+,	O
+a	O
+recently	O
+described	O
+member	O
+of	O
+the	O
+hepatocyte	B-GENE
+nuclear	I-GENE
+factor	I-GENE
+3	I-GENE
+/	O
+forkhead	B-GENE
+homeotic	B-GENE
+gene	I-GENE
+family	I-GENE
+,	O
+as	O
+a	O
+nuclear	B-GENE
+hormone	I-GENE
+receptor	I-GENE
+(	O
+NR	B-GENE
+)	O
+intermediary	O
+protein	O
+.	O
+
+The	O
+improved	O
+CSF	O
+outflow	O
+conductance	O
+may	O
+increase	O
+the	O
+intracranial	O
+compliance	O
+and	O
+thereby	O
+dampen	O
+a	O
+pathological	O
+ICP	O
+waveform	O
+.	O
+
+A	O
+new	O
+species	O
+of	O
+Euspondylus	O
+is	O
+described	O
+based	O
+on	O
+a	O
+female	O
+(	O
+taken	O
+within	O
+a	O
+bromeliad	O
+)	O
+from	O
+Cerro	O
+El	O
+Humo	O
+,	O
+Sucre	O
+,	O
+northeastern	O
+Venezuela	O
+.	O
+
+The	O
+cyclins	B-GENE
+bind	O
+to	O
+and	O
+activate	O
+the	O
+CDK	B-GENE
+,	O
+which	O
+leads	O
+to	O
+phosphorylation	O
+(	O
+and	O
+then	O
+inhibition	O
+)	O
+of	O
+the	O
+tumor	O
+suppressor	O
+protein	O
+,	O
+pRb	B-GENE
+.	O
+pRb	B-GENE
+controls	O
+commitment	O
+to	O
+progress	O
+from	O
+the	O
+G1	O
+to	O
+S	O
+phase	O
+,	O
+at	O
+least	O
+in	O
+part	O
+by	O
+repressing	O
+the	O
+activity	O
+of	O
+the	O
+E2F	B-GENE
+transcription	I-GENE
+factors	I-GENE
+known	O
+to	O
+promote	O
+cell	O
+proliferation	O
+.	O
+
+Additional	O
+education	O
+and	O
+research	O
+is	O
+needed	O
+to	O
+provide	O
+further	O
+direction	O
+for	O
+intervention	O
+and	O
+incorporation	O
+into	O
+practice	O
+.	O
+
+Proliferative	O
+vasculopathy	O
+and	O
+cutaneous	O
+hemorrhages	O
+in	O
+porcine	O
+neonates	O
+infected	O
+with	O
+the	O
+porcine	O
+reproductive	O
+and	O
+respiratory	O
+syndrome	O
+virus	O
+.	O
+
+The	O
+difference	O
+of	O
+hardness	O
+over	O
+time	O
+of	O
+composite	O
+specimens	O
+was	O
+measured	O
+using	O
+Knoop	O
+hardness	O
+measurements	O
+taken	O
+at	O
+the	O
+top	O
+and	O
+bottom	O
+surfaces	O
+of	O
+resin	O
+specimens	O
+made	O
+in	O
+a	O
+Teflon	O
+mold	O
+the	O
+same	O
+dimensions	O
+as	O
+the	O
+cavity	O
+prepared	O
+in	O
+dentin	O
+.	O
+
+An	O
+18	O
+-	O
+kb	O
+genomic	O
+clone	O
+including	O
+sequences	O
+encoding	O
+for	O
+the	O
+two	O
+GHS	B-GENE
+-	I-GENE
+R	I-GENE
+variants	I-GENE
+was	O
+isolated	O
+.	O
+
+Saccharomyces	O
+cerevisiae	O
+activates	O
+a	O
+regulatory	O
+network	O
+called	O
+"	O
+general	O
+control	O
+"	O
+that	O
+provides	O
+the	O
+cell	O
+with	O
+sufficient	O
+amounts	O
+of	O
+protein	O
+precursors	O
+during	O
+amino	O
+acid	O
+starvation	O
+.	O
+
+In	O
+Ka13	O
+cells	O
+,	O
+CoCl	O
+(	O
+2	O
+)	O
+stimulated	O
+expression	O
+of	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+under	O
+the	O
+control	O
+of	O
+a	O
+15	B-GENE
+-	I-GENE
+kilobase	I-GENE
+pair	I-GENE
+mouse	I-GENE
+ho	I-GENE
+-	I-GENE
+1	I-GENE
+promoter	I-GENE
+(	O
+pHO15luc	B-GENE
+)	O
+.	O
+
+Mutation	O
+analyses	O
+identified	O
+the	O
+cobalt	O
+-	O
+responsive	O
+sequences	O
+as	O
+the	O
+stress	O
+-	O
+response	O
+elements	O
+(	O
+StREs	O
+)	O
+.	O
+
+Members	O
+of	O
+the	O
+AP	B-GENE
+-	I-GENE
+1	I-GENE
+superfamily	I-GENE
+of	I-GENE
+basic	I-GENE
+-	I-GENE
+leucine	I-GENE
+zipper	I-GENE
+factors	I-GENE
+bind	O
+to	O
+the	O
+StRE	O
+.	O
+
+Descriptions	O
+of	O
+this	O
+locus	O
+would	O
+allow	O
+comparison	O
+with	O
+functionally	O
+relevant	O
+molecular	O
+genetic	O
+features	O
+of	O
+other	O
+species	O
+'	O
+homologous	O
+loci	O
+including	O
+the	O
+single	O
+-	O
+copy	O
+equid	O
+LH	B-GENE
+/	O
+CGbeta	B-GENE
+gene	O
+and	O
+the	O
+primate	O
+LHbeta	B-GENE
+-	O
+CGbeta	B-GENE
+gene	O
+cluster	O
+locus	O
+.	O
+
+Like	O
+the	O
+consensus	B-GENE
+mammalian	I-GENE
+LHbeta	I-GENE
+gene	I-GENE
+,	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+gpLH	B-GENE
+/	O
+CGbeta	B-GENE
+gene	O
+contains	O
+a	O
+single	O
+TATA	O
+sequence	O
+37	O
+bp	O
+upstream	O
+of	O
+the	O
+translation	O
+start	O
+codon	O
+.	O
+
+This	O
+shows	O
+that	O
+in	O
+situations	O
+of	O
+separated	O
+breaks	O
+,	O
+NHEJ	O
+deficiency	O
+leads	O
+to	O
+genomic	O
+rearrangements	O
+,	O
+in	O
+agreement	O
+with	O
+chromosomal	O
+studies	O
+.	O
+
+Foxp1	B-GENE
+and	O
+Foxp2	B-GENE
+are	O
+expressed	O
+at	O
+high	O
+levels	O
+in	O
+the	O
+lung	O
+as	O
+early	O
+as	O
+E12	O
+.	O
+5	O
+of	O
+mouse	O
+development	O
+with	O
+Foxp2	B-GENE
+expression	O
+restricted	O
+to	O
+the	O
+airway	O
+epithelium	O
+.	O
+
+Immunological	O
+and	O
+biochemical	O
+characterization	O
+of	O
+streptococcal	B-GENE
+pyrogenic	I-GENE
+exotoxins	I-GENE
+I	I-GENE
+and	I-GENE
+J	I-GENE
+(	O
+SPE	B-GENE
+-	I-GENE
+I	I-GENE
+and	O
+SPE	B-GENE
+-	I-GENE
+J	I-GENE
+)	O
+from	O
+Streptococcus	O
+pyogenes	O
+.	O
+
+Several	O
+dozen	O
+HIF	B-GENE
+-	I-GENE
+1	I-GENE
+targets	I-GENE
+are	O
+known	O
+,	O
+including	O
+the	O
+gene	O
+encoding	O
+vascular	B-GENE
+endothelial	I-GENE
+growth	I-GENE
+factor	I-GENE
+(	O
+VEGF	B-GENE
+)	O
+.	O
+
+We	O
+previously	O
+reported	O
+that	O
+Tax	B-GENE
+induced	O
+cell	O
+cycle	O
+progression	O
+from	O
+G0	O
+/	O
+G1	O
+phase	O
+to	O
+S	O
+and	O
+G2	O
+/	O
+M	O
+phases	O
+in	O
+human	O
+T	O
+-	O
+cell	O
+line	O
+Kit	O
+225	O
+cells	O
+.	O
+
+Most	O
+yeast	B-GENE
+peroxisomal	I-GENE
+matrix	I-GENE
+proteins	I-GENE
+contain	O
+a	O
+type	O
+1C	O
+-	O
+terminal	O
+peroxisomal	O
+targeting	O
+signal	O
+(	O
+PTS1	O
+)	O
+consisting	O
+of	O
+the	O
+tripeptide	O
+SKL	O
+or	O
+a	O
+conservative	O
+variant	O
+thereof	O
+.	O
+
+Here	O
+,	O
+the	O
+PEX5	B-GENE
+-	O
+TPR	O
+domains	O
+from	O
+human	O
+,	O
+tobacco	O
+,	O
+and	O
+nematode	O
+were	O
+inserted	O
+into	O
+a	O
+TPR	O
+-	O
+less	O
+yeast	O
+Pex5p	B-GENE
+construct	O
+to	O
+generate	O
+Pex5p	B-GENE
+chimaeras	O
+.	O
+
+HIV	O
+-	O
+1	O
+and	O
+hepatitis	O
+B	O
+virus	O
+infections	O
+in	O
+adolescents	O
+lodged	O
+in	O
+security	O
+institutes	O
+of	O
+Buenos	O
+Aires	O
+.	O
+
+Immunofixation	O
+experiments	O
+of	O
+C4A	B-GENE
+and	O
+C4B	B-GENE
+demonstrate	O
+>	O
+41	O
+allotypes	O
+in	O
+the	O
+two	O
+classes	O
+of	O
+proteins	O
+.	O
+
+However	O
+,	O
+C4B	B-GENE
+proteins	I-GENE
+encoded	O
+by	O
+monomodular	O
+short	O
+genes	O
+may	O
+have	O
+relatively	O
+higher	O
+concentrations	O
+than	O
+those	O
+from	O
+long	B-GENE
+C4A	I-GENE
+genes	I-GENE
+.	O
+
+In	O
+the	O
+course	O
+of	O
+screening	O
+for	O
+transcription	O
+factors	O
+which	O
+interact	O
+with	O
+the	O
+human	B-GENE
+myeloperoxidase	I-GENE
+(	O
+MPO	B-GENE
+)	O
+promoter	O
+we	O
+,	O
+for	O
+the	O
+first	O
+time	O
+,	O
+identified	O
+and	O
+cloned	O
+the	O
+cDNA	O
+and	O
+genomic	O
+DNA	O
+for	O
+human	B-GENE
+HBP1	I-GENE
+(	O
+HMG	B-GENE
+-	I-GENE
+Box	I-GENE
+containing	I-GENE
+protein	I-GENE
+1	I-GENE
+)	O
+,	O
+a	O
+member	O
+of	O
+the	O
+high	B-GENE
+mobility	I-GENE
+group	I-GENE
+of	I-GENE
+non	I-GENE
+-	I-GENE
+histone	I-GENE
+chromosomal	I-GENE
+proteins	I-GENE
+.	O
+
+The	O
+human	O
+protein	O
+sequence	O
+exhibits	O
+a	O
+putative	O
+DNA	O
+-	O
+binding	O
+domain	O
+similar	O
+to	O
+that	O
+seen	O
+in	O
+rat	B-GENE
+HBP1	I-GENE
+and	O
+shows	O
+homology	O
+with	O
+the	O
+activation	O
+and	O
+repressor	O
+domains	O
+previously	O
+demonstrated	O
+in	O
+the	O
+rat	O
+protein	O
+.	O
+
+Promoter	O
+transcriptional	O
+activity	O
+was	O
+determined	O
+for	O
+a	O
+wide	O
+5	O
+'	O
+portion	O
+of	O
+the	O
+human	O
+annexin	B-GENE
+A5	I-GENE
+gene	I-GENE
+,	O
+from	O
+bp	O
+-	O
+1275	O
+to	O
++	O
+79	O
+relative	O
+to	O
+the	O
+most	O
+5	O
+'	O
+of	O
+several	O
+discrete	O
+transcription	O
+start	O
+points	O
+.	O
+
+In	O
+contrast	O
+the	O
+human	O
+and	O
+mouse	B-GENE
+BCNT	I-GENE
+proteins	I-GENE
+contain	O
+one	O
+repeat	O
+unit	O
+and	O
+lack	O
+the	O
+RTE	B-GENE
+-	I-GENE
+1	I-GENE
+-	O
+derived	O
+portion	O
+.	O
+
+Molecular	O
+identification	O
+of	O
+smg	B-GENE
+-	I-GENE
+4	I-GENE
+,	O
+required	O
+for	O
+mRNA	O
+surveillance	O
+in	O
+C	O
+.	O
+elegans	O
+.	O
+
+Two	O
+remotely	O
+situated	O
+exons	O
+within	O
+the	O
+complement	B-GENE
+C3	I-GENE
+gene	O
+locus	O
+encode	O
+an	O
+alternate	O
+5	O
+'	O
+end	O
+and	O
+proximal	O
+ORF	O
+under	O
+the	O
+control	O
+of	O
+a	O
+bidirectional	O
+promoter	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Adding	O
+MMF	O
+,	O
+a	O
+potent	O
+topical	O
+corticosteroid	O
+,	O
+to	O
+an	O
+emollient	O
+cream	O
+is	O
+statistically	O
+significantly	O
+more	O
+effective	O
+than	O
+emollient	O
+cream	O
+alone	O
+in	O
+reducing	O
+acute	O
+radiation	O
+dermatitis	O
+.	O
+
+Recent	O
+advances	O
+have	O
+shown	O
+that	O
+volatile	O
+sulfur	O
+is	O
+a	O
+result	O
+of	O
+ecological	O
+interactions	O
+and	O
+transformation	O
+processes	O
+through	O
+planktonic	O
+food	O
+webs	O
+.	O
+
+The	O
+first	O
+hypothesis	O
+was	O
+supported	O
+in	O
+the	O
+sense	O
+that	O
+stimulus	O
+differences	O
+might	O
+affect	O
+behaviour	O
+even	O
+without	O
+their	O
+successful	O
+attentive	O
+processing	O
+in	O
+normal	O
+participants	O
+.	O
+
+There	O
+was	O
+an	O
+increase	O
+in	O
+protein	O
+binding	O
+onto	O
+this	O
+element	O
+only	O
+after	O
+peptide	O
+treatment	O
+.	O
+
+CSR	O
+is	O
+directed	O
+to	O
+specific	O
+heavy	O
+chain	O
+isotypes	O
+by	O
+cytokines	O
+and	O
+B	O
+cell	O
+activators	O
+that	O
+induce	O
+transcription	O
+from	O
+the	O
+unrearranged	O
+,	O
+or	O
+germline	O
+(	O
+GL	O
+)	O
+,	O
+C	B-GENE
+(	I-GENE
+H	I-GENE
+)	I-GENE
+region	I-GENE
+genes	I-GENE
+.	O
+
+In	O
+this	O
+manuscript	O
+we	O
+demonstrate	O
+that	O
+two	O
+tandem	B-GENE
+Ets	I-GENE
+sites	I-GENE
+in	O
+the	O
+mouse	B-GENE
+GL	I-GENE
+alpha	I-GENE
+promoter	I-GENE
+bind	O
+the	O
+transcription	B-GENE
+factors	I-GENE
+Elf	I-GENE
+-	I-GENE
+1	I-GENE
+and	O
+PU	B-GENE
+.	I-GENE
+1	I-GENE
+,	O
+and	O
+that	O
+the	O
+3	O
+'	O
+site	O
+is	O
+essential	O
+for	O
+expression	O
+of	O
+a	O
+luciferase	B-GENE
+reporter	I-GENE
+gene	I-GENE
+driven	O
+by	O
+the	O
+GL	B-GENE
+alpha	I-GENE
+promoter	I-GENE
+.	O
+
+Cell	O
+.	O
+
+The	O
+mean	O
+serum	O
+creatinine	O
+level	O
+did	O
+not	O
+change	O
+during	O
+the	O
+first	O
+6	O
+months	O
+after	O
+withdrawal	O
+of	O
+MMF	O
+.	O
+
+The	O
+proportion	O
+of	O
+the	O
+biopsies	O
+found	O
+to	O
+be	O
+seropositive	O
+for	O
+HBs	B-GENE
+antigen	I-GENE
+was	O
+27	O
+.	O
+9	O
+%	O
+,	O
+and	O
+these	O
+showed	O
+either	O
+MGN	O
+or	O
+MPGN	O
+pattern	O
+.	O
+
+They	O
+correspond	O
+to	O
+nucleotides	O
+equivalent	O
+to	O
+base	O
+-	O
+pair	O
+C1	O
+-	O
+G72	O
+and	O
+discriminator	O
+base	O
+A73	O
+in	O
+the	O
+amino	O
+acid	O
+-	O
+acceptor	O
+branch	O
+of	O
+the	O
+molecule	O
+.	O
+
+This	O
+domain	O
+without	O
+the	O
+canonical	O
+anticodon	O
+loop	O
+or	O
+the	O
+tyrosine	O
+anticodon	O
+acts	O
+as	O
+an	O
+anchor	O
+for	O
+TyrRS	B-GENE
+interaction	O
+leading	O
+to	O
+a	O
+better	O
+efficiency	O
+of	O
+tyrosylation	O
+.	O
+
+During	O
+most	O
+of	O
+the	O
+cell	O
+cycle	O
+,	O
+separase	B-GENE
+is	O
+kept	O
+inactive	O
+by	O
+binding	O
+to	O
+an	O
+inhibitory	O
+protein	O
+called	O
+securin	B-GENE
+.	O
+
+Mechanical	O
+ventilation	O
+in	O
+control	O
+lungs	O
+produced	O
+a	O
+47	O
+%	O
+decrease	O
+in	O
+chord	O
+compliance	O
+,	O
+an	O
+increase	O
+in	O
+lung	O
+lavage	O
+levels	O
+of	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+(	I-GENE
+TNF	I-GENE
+)	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+722	O
++	O
+/	O
+-	O
+306	O
+pg	O
+/	O
+ml	O
+)	O
+,	O
+interleukin	B-GENE
+(	I-GENE
+IL	I-GENE
+)	I-GENE
+-	I-GENE
+1beta	I-GENE
+(	O
+902	O
++	O
+/	O
+-	O
+322	O
+pg	O
+/	O
+ml	O
+)	O
+,	O
+and	O
+macrophage	B-GENE
+inflammatory	I-GENE
+protein	I-GENE
+-	I-GENE
+2	I-GENE
+(	O
+MIP	B-GENE
+-	I-GENE
+2	I-GENE
+)	O
+(	O
+363	O
++	O
+/	O
+-	O
+104	O
+pg	O
+/	O
+ml	O
+)	O
+as	O
+compared	O
+with	O
+low	O
+levels	O
+of	O
+cytokines	O
+detected	O
+in	O
+preventilation	O
+data	O
+,	O
+and	O
+no	O
+change	O
+in	O
+percentage	O
+of	O
+surfactant	O
+large	O
+aggregates	O
+(	O
+LA	O
+)	O
+.	O
+
+Maternal	O
+p	O
+,	O
+p	O
+'	O
+DDE	O
+and	O
+beta	O
+-	O
+HCH	O
+levels	O
+were	O
+also	O
+associated	O
+with	O
+newborn	O
+levels	O
+,	O
+but	O
+levels	O
+of	O
+PCBs	O
+were	O
+not	O
+.	O
+
+Multiple	O
+regression	O
+analysis	O
+performed	O
+between	O
+these	O
+long	O
+-	O
+term	O
+abiotic	O
+factors	O
+and	O
+nymphal	O
+abundance	O
+in	O
+positive	O
+sites	O
+showed	O
+high	O
+relationship	O
+(	O
+R2	O
+coefficients	O
+)	O
+for	O
+every	O
+habitat	O
+category	O
+and	O
+explained	O
+>	O
+50	O
+%	O
+of	O
+the	O
+variation	O
+in	O
+tick	O
+abundance	O
+.	O
+
+In	O
+summary	O
+,	O
+we	O
+conclude	O
+that	O
+the	O
+adenoviral	O
+oncoprotein	O
+E1A	B-GENE
+activates	O
+transcription	O
+from	O
+the	O
+endogenous	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+gene	I-GENE
+,	O
+an	O
+effect	O
+that	O
+involves	O
+transcriptional	O
+derepression	O
+of	O
+the	O
+AP	B-GENE
+-	I-GENE
+2alpha	I-GENE
+promoter	I-GENE
+by	O
+interaction	O
+of	O
+E1A	B-GENE
+with	O
+the	O
+AP	B-GENE
+-	I-GENE
+2rep	I-GENE
+corepressor	O
+CtBP1	B-GENE
+.	O
+
+Additional	O
+factors	O
+such	O
+as	O
+advanced	O
+age	O
+,	O
+concomitant	O
+use	O
+of	O
+corticosteroids	O
+or	O
+anticoagulants	O
+,	O
+prior	O
+ulcer	O
+complications	O
+and	O
+co	O
+-	O
+morbid	O
+diseases	O
+may	O
+further	O
+increase	O
+the	O
+risk	O
+of	O
+bleeding	O
+.	O
+
+The	O
+core	O
+promoter	O
+of	O
+human	B-GENE
+thioredoxin	I-GENE
+reductase	I-GENE
+1	I-GENE
+:	O
+cloning	O
+,	O
+transcriptional	O
+activity	O
+,	O
+and	O
+Oct	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+Sp1	B-GENE
+,	O
+and	O
+Sp3	B-GENE
+binding	O
+reveal	O
+a	O
+housekeeping	O
+-	O
+type	O
+promoter	O
+for	O
+the	O
+AU	O
+-	O
+rich	O
+element	O
+-	O
+regulated	O
+gene	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+phosphorylation	O
+-	O
+induced	O
+loss	O
+of	O
+the	O
+protein	O
+kinase	O
+activity	O
+of	O
+DNA	B-GENE
+-	I-GENE
+PK	I-GENE
+is	O
+restored	O
+by	O
+the	O
+addition	O
+of	O
+the	O
+purified	O
+catalytic	O
+subunit	O
+of	O
+either	O
+protein	B-GENE
+phosphatase	I-GENE
+1	I-GENE
+or	O
+protein	B-GENE
+phosphatase	I-GENE
+2A	I-GENE
+(	O
+PP2A	B-GENE
+)	O
+and	O
+that	O
+this	O
+reactivation	O
+is	O
+blocked	O
+by	O
+the	O
+potent	O
+protein	O
+phosphatase	O
+inhibitor	O
+,	O
+microcystin	O
+.	O
+
+The	O
+first	O
+exon	O
+(	O
+exon	O
+1A	O
+)	O
+that	O
+corresponded	O
+to	O
+the	O
+5	O
+'	O
+-	O
+untranslated	O
+region	O
+of	O
+the	O
+GHR	B-GENE
+1A	I-GENE
+mRNA	I-GENE
+was	O
+15	O
+,	O
+250	O
+bp	O
+upstream	O
+from	O
+exon	O
+2	O
+in	O
+the	O
+GHR	B-GENE
+gene	I-GENE
+.	O
+
+FLP	B-GENE
+and	O
+Cre	B-GENE
+recombinase	I-GENE
+function	O
+in	O
+Xenopus	O
+embryos	O
+.	O
+
+A	O
+method	O
+of	O
+three	O
+-	O
+station	O
+three	O
+-	O
+dimensional	O
+magnetic	O
+resonance	O
+(	O
+MR	O
+)	O
+angiography	O
+of	O
+the	O
+lower	O
+extremities	O
+with	O
+segmented	O
+volume	O
+acquisition	O
+is	O
+presented	O
+.	O
+
+A	O
+single	O
+nucleotide	O
+polymorphism	O
+(	O
+SNP	O
+)	O
+in	O
+exon	O
+2	O
+,	O
+which	O
+is	O
+tightly	O
+liked	O
+to	O
+another	O
+SNP	O
+(	O
+GTG83	O
+/	O
+ATG83	O
+)	O
+,	O
+creates	O
+an	O
+additional	O
+alternative	O
+in	O
+-	O
+frame	O
+AUG	O
+in	O
+B	B-GENE
+-	I-GENE
+type	I-GENE
+MTH1	I-GENE
+mRNAs	I-GENE
+yielding	O
+the	O
+fourth	O
+MTH1	B-GENE
+polypeptide	I-GENE
+,	O
+p26	B-GENE
+that	O
+possesses	O
+an	O
+additional	O
+mitochondrial	O
+targeting	O
+signal	O
+.	O
+
+Our	O
+previous	O
+studies	O
+have	O
+shown	O
+that	O
+SHP	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+a	O
+SH2	B-GENE
+domain	I-GENE
+-	I-GENE
+containing	I-GENE
+protein	I-GENE
+-	I-GENE
+tyrosine	I-GENE
+phosphatase	I-GENE
+,	O
+is	O
+expressed	O
+not	O
+only	O
+in	O
+cells	O
+of	O
+hematopoietic	O
+lineages	O
+,	O
+but	O
+also	O
+in	O
+many	O
+non	O
+-	O
+hematopoietic	O
+cells	O
+under	O
+the	O
+control	O
+of	O
+an	O
+alternative	O
+tissue	O
+-	O
+specific	O
+promoter	O
+,	O
+P1	O
+.	O
+
+Unexpectedly	O
+,	O
+Arg1	B-GENE
+-	O
+expressing	O
+COS1	O
+cells	O
+showed	O
+no	O
+significant	O
+proteinase	O
+activity	O
+to	O
+various	O
+synthesized	O
+substrates	O
+under	O
+neutral	O
+or	O
+acidic	O
+conditions	O
+in	O
+this	O
+study	O
+.	O
+
+ORF1	O
+(	O
+1029	O
+bp	O
+;	O
+EMBL	O
+databank	O
+,	O
+Accession	O
+No	O
+.	O
+
+In	O
+the	O
+meantime	O
+,	O
+one	O
+has	O
+succeeded	O
+to	O
+establish	O
+the	O
+deammonification	O
+processes	O
+in	O
+a	O
+continuous	O
+flow	O
+moving	O
+-	O
+bed	O
+pilot	O
+plant	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+simplified	O
+methods	O
+for	O
+estimation	O
+of	O
+Technetium	O
+Tc	O
+99m	O
+(	O
+99mTc	O
+)	O
+-	O
+pentetate	O
+and	O
+orthoiodohippurate	O
+I	O
+131	O
+(	O
+131I	O
+-	O
+OIH	O
+)	O
+plasma	O
+clearance	O
+in	O
+dogs	O
+and	O
+cats	O
+with	O
+1	O
+and	O
+2	O
+blood	O
+samples	O
+.	O
+
+Interventions	O
+aimed	O
+at	O
+these	O
+specific	O
+mediators	O
+and	O
+processes	O
+may	O
+be	O
+successful	O
+in	O
+reducing	O
+the	O
+very	O
+significant	O
+human	O
+and	O
+economic	O
+costs	O
+of	O
+vascular	O
+access	O
+dysfunction	O
+.	O
+
+In	O
+addition	O
+,	O
+stonin	B-GENE
+2	I-GENE
+binds	O
+to	O
+the	O
+C2B	O
+domains	O
+of	O
+synaptotagmins	B-GENE
+I	I-GENE
+and	I-GENE
+II	I-GENE
+.	O
+
+This	O
+partial	O
+transection	O
+could	O
+permit	O
+vasopressin	B-GENE
+to	O
+be	O
+secreted	O
+in	O
+response	O
+to	O
+a	O
+larger	O
+rise	O
+in	O
+plasma	O
+sodium	O
+concentration	O
+.	O
+
+In	O
+conclusion	O
+,	O
+USPIO	O
+-	O
+enhanced	O
+MRI	O
+data	O
+were	O
+capable	O
+to	O
+characterize	O
+tumor	O
+microvessel	O
+properties	O
+in	O
+this	O
+breast	O
+cancer	O
+model	O
+:	O
+microvascular	O
+permeability	O
+(	O
+determined	O
+using	O
+USPIO	O
+)	O
+correlated	O
+significantly	O
+with	O
+tumor	O
+grade	O
+.	O
+
+However	O
+,	O
+the	O
+N63S	O
+mutation	O
+in	O
+the	O
+wild	B-GENE
+-	I-GENE
+type	I-GENE
+VP5	I-GENE
+background	O
+increased	O
+the	O
+interaction	O
+,	O
+as	O
+judged	O
+by	O
+the	O
+beta	B-GENE
+-	I-GENE
+galactosidase	I-GENE
+activity	O
+,	O
+by	O
+a	O
+factor	O
+of	O
+9	O
+relative	O
+to	O
+when	O
+the	O
+PR7	O
+mutation	O
+was	O
+present	O
+.	O
+
+An	O
+integrated	O
+RTC	O
+algorithm	O
+for	O
+the	O
+urban	O
+wastewater	O
+system	O
+is	O
+formulated	O
+,	O
+the	O
+parameters	O
+of	O
+which	O
+are	O
+optimized	O
+using	O
+various	O
+global	O
+optimization	O
+routines	O
+.	O
+
+SKP1	B-GENE
+-	O
+SnRK	B-GENE
+protein	O
+kinase	O
+interactions	O
+mediate	O
+proteasomal	O
+binding	O
+of	O
+a	O
+plant	O
+SCF	B-GENE
+ubiquitin	I-GENE
+ligase	I-GENE
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Between	O
+June	O
+1991	O
+and	O
+December	O
+1996	O
+,	O
+we	O
+administered	O
+the	O
+nucleoside	O
+analog	O
+2	O
+-	O
+chlorodeoxyadenosine	O
+(	O
+2	O
+-	O
+CDA	O
+)	O
+to	O
+73	O
+children	O
+with	O
+primary	O
+AML	O
+and	O
+20	O
+children	O
+with	O
+secondary	O
+AML	O
+or	O
+myelodysplastic	O
+syndrome	O
+(	O
+MDS	O
+)	O
+.	O
+
+The	O
+severity	O
+of	O
+pathologic	O
+changes	O
+increased	O
+with	O
+the	O
+magnitude	O
+of	O
+percussion	O
+.	O
+
+Experimental	O
+study	O
+of	O
+ta	O
+chengchi	O
+tang	O
+decoction	O
+for	O
+relieving	O
+lung	O
+injury	O
+during	O
+acute	O
+necrotizing	O
+pancreatitis	O
+]	O
+The	O
+objectives	O
+of	O
+the	O
+study	O
+were	O
+to	O
+investigate	O
+the	O
+changes	O
+of	O
+leukocyte	O
+adhesiveness	O
+and	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+(	O
+TNF	B-GENE
+)	O
+in	O
+the	O
+early	O
+stage	O
+of	O
+acute	O
+necrotizing	O
+pancreatitis	O
+(	O
+ANP	O
+)	O
+,	O
+to	O
+go	O
+further	O
+into	O
+the	O
+relation	O
+of	O
+those	O
+changes	O
+to	O
+lung	O
+injury	O
+of	O
+ANP	O
+,	O
+and	O
+to	O
+evaluate	O
+the	O
+prohibitive	O
+effect	O
+of	O
+ta	O
+chengchi	O
+tang	O
+Decoction	O
+on	O
+leukocyte	O
+adhesion	O
+and	O
+TNF	B-GENE
+secretion	O
+.	O
+
+A	O
+variety	O
+of	O
+receptor	O
+-	O
+mediated	O
+signaling	O
+pathways	O
+are	O
+controlled	O
+by	O
+both	O
+positive	O
+and	O
+negative	O
+extracellular	O
+regulators	O
+.	O
+
+TT	O
+cells	O
+,	O
+a	O
+human	O
+MTC	O
+cell	O
+line	O
+expressing	O
+MEN	B-GENE
+2A	I-GENE
+type	I-GENE
+RET	I-GENE
+,	O
+display	O
+transcriptionally	O
+active	O
+RelA	B-GENE
+(	I-GENE
+p65	I-GENE
+)	I-GENE
+in	O
+the	O
+nucleus	O
+.	O
+
+Inhibition	O
+of	O
+constitutive	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+activity	O
+results	O
+in	O
+cell	O
+death	O
+of	O
+TT	O
+cells	O
+and	O
+blocks	O
+focus	O
+formation	O
+induced	O
+by	O
+oncogenic	O
+forms	O
+of	O
+RET	B-GENE
+in	O
+NIH	O
+3T3	O
+cells	O
+.	O
+
+Reciprocally	O
+,	O
+HMGI	B-GENE
+-	I-GENE
+C	I-GENE
+expression	O
+also	O
+coordinately	O
+enhances	O
+PIAS3	B-GENE
+-	O
+mediated	O
+repression	O
+of	O
+STAT3	B-GENE
+-	O
+dependent	O
+transactivation	O
+.	O
+
+A	O
+central	O
+finding	O
+is	O
+the	O
+identification	O
+of	O
+a	O
+GC	O
+-	O
+rich	O
+sequence	O
+in	O
+the	O
+-	O
+99	O
+/	O
+-	O
+91	O
+Cp	B-GENE
+region	O
+that	O
+is	O
+essential	O
+for	O
+oriPI	O
+-	O
+EBNA1	B-GENE
+-	O
+independent	O
+as	O
+well	O
+as	O
+oriPI	O
+-	O
+EBNA1	B-GENE
+-	O
+dependent	O
+activity	O
+of	O
+the	O
+promoter	O
+.	O
+
+Additional	O
+deletion	O
+mutations	O
+revealed	O
+a	O
+new	O
+,	O
+67	O
+-	O
+amino	O
+-	O
+acid	O
+functional	O
+domain	O
+within	O
+the	O
+proline	O
+-	O
+rich	O
+region	O
+of	O
+SLP	B-GENE
+-	I-GENE
+76	I-GENE
+,	O
+which	O
+we	O
+have	O
+termed	O
+the	O
+P	O
+-	O
+1	O
+domain	O
+.	O
+
+Finally	O
+,	O
+profiling	O
+of	O
+a	O
+gcn4Delta	B-GENE
+mutant	I-GENE
+uncovered	O
+an	O
+alternative	O
+induction	O
+pathway	O
+operating	O
+at	O
+many	O
+Gcn4p	B-GENE
+target	I-GENE
+genes	I-GENE
+in	O
+histidine	O
+-	O
+starved	O
+cells	O
+.	O
+
+Evidence	O
+from	O
+a	O
+Northern	O
+hybridization	O
+indicated	O
+that	O
+jadM	B-GENE
+expression	O
+is	O
+correlated	O
+with	O
+jadomycin	B-GENE
+B	I-GENE
+synthesis	O
+.	O
+
+Right	O
+LHR	O
+(	O
+R	O
+-	O
+LHR	O
+)	O
+provided	O
+the	O
+best	O
+interobserver	O
+and	O
+intraobserver	O
+reproducibility	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+methodology	O
+of	O
+LHR	O
+measurement	O
+significantly	O
+influences	O
+the	O
+clinical	O
+contribution	O
+of	O
+Tl	O
+-	O
+201	O
+lung	O
+uptake	O
+evaluation	O
+.	O
+
+Mutation	O
+of	O
+the	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+site	I-GENE
+in	O
+the	O
+Mdr1b	B-GENE
+promoter	I-GENE
+prevents	O
+its	O
+induction	O
+by	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+.	O
+
+To	O
+determine	O
+the	O
+genomic	O
+complexity	O
+of	O
+the	O
+deleted	O
+region	O
+shared	O
+among	O
+tumors	O
+,	O
+we	O
+assembled	O
+a	O
+physical	O
+map	O
+of	O
+the	O
+I	O
+Mbp	O
+SRO	O
+consisting	O
+predominantly	O
+of	O
+bacteriophage	O
+P1	O
+-	O
+derived	O
+artificial	O
+chromosome	O
+(	O
+PAC	O
+)	O
+clones	O
+.	O
+
+Online	O
+teaching	O
+:	O
+design	O
+and	O
+techniques	O
+.	O
+
+Data	O
+were	O
+obtained	O
+from	O
+2	O
+undergraduate	O
+student	O
+samples	O
+,	O
+a	O
+self	O
+-	O
+report	O
+group	O
+(	O
+n	O
+=	O
+132	O
+)	O
+who	O
+provided	O
+NEO	O
+-	O
+PI	O
+-	O
+R	O
+self	O
+-	O
+ratings	O
+on	O
+2	O
+occasions	O
+separated	O
+by	O
+a	O
+7	O
+-	O
+to	O
+14	O
+-	O
+day	O
+interval	O
+and	O
+an	O
+informant	O
+group	O
+(	O
+n	O
+=	O
+109	O
+)	O
+who	O
+provided	O
+ratings	O
+of	O
+well	O
+-	O
+known	O
+friends	O
+or	O
+relatives	O
+on	O
+2	O
+occasions	O
+separated	O
+by	O
+a	O
+6	O
+month	O
+interval	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+of	O
+RNAs	O
+from	O
+a	O
+number	O
+of	O
+mouse	O
+tissues	O
+reveals	O
+that	O
+Atp6i	B-GENE
+is	O
+expressed	O
+predominantly	O
+in	O
+osteoclasts	O
+,	O
+and	O
+this	O
+predominant	O
+expression	O
+was	O
+confirmed	O
+by	O
+reverse	O
+-	O
+transcription	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+RT	O
+-	O
+PCR	O
+)	O
+assay	O
+and	O
+immunohistochemical	O
+analysis	O
+.	O
+
+Indeed	O
+,	O
+mutation	O
+of	O
+two	O
+of	O
+these	O
+motifs	O
+,	O
+known	O
+to	O
+be	O
+important	O
+to	O
+regulation	O
+of	O
+sid1	B-GENE
+,	O
+altered	O
+the	O
+differential	O
+regulation	O
+of	O
+sid2	B-GENE
+by	O
+iron	O
+.	O
+
+The	O
+described	O
+results	O
+show	O
+that	O
+DTD	O
+is	O
+fast	O
+,	O
+simple	O
+,	O
+and	O
+easy	O
+to	O
+automate	O
+;	O
+requires	O
+only	O
+a	O
+small	O
+amount	O
+of	O
+sample	O
+(	O
+approximately	O
+50	O
+mg	O
+)	O
+;	O
+and	O
+affords	O
+quantitative	O
+information	O
+about	O
+the	O
+main	O
+groups	O
+of	O
+compounds	O
+present	O
+in	O
+cheeses	O
+.	O
+
+Guidelines	O
+for	O
+performing	O
+a	O
+routine	O
+spiral	O
+assay	O
+are	O
+presented	O
+,	O
+and	O
+alternative	O
+test	O
+methods	O
+intended	O
+to	O
+overcome	O
+a	O
+variety	O
+of	O
+technical	O
+difficulties	O
+(	O
+such	O
+as	O
+restricted	O
+sample	O
+availability	O
+,	O
+sample	O
+viscosity	O
+or	O
+volatility	O
+,	O
+etc	O
+.	O
+)	O
+are	O
+recommended	O
+.	O
+
+In	O
+conclusion	O
+,	O
+obesity	O
+,	O
+alcohol	O
+intake	O
+,	O
+and	O
+multimetabolic	O
+disorders	O
+were	O
+determined	O
+to	O
+be	O
+independent	O
+predictors	O
+for	O
+the	O
+development	O
+of	O
+hyperuricemia	O
+.	O
+
+Autoregulation	O
+enables	O
+different	O
+pathways	O
+to	O
+control	O
+CCAAT	B-GENE
+/	I-GENE
+enhancer	I-GENE
+binding	I-GENE
+protein	I-GENE
+beta	I-GENE
+(	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+)	O
+transcription	O
+.	O
+
+As	O
+a	O
+reflection	O
+of	O
+uncertainties	O
+in	O
+the	O
+estimates	O
+for	O
+individual	O
+sources	O
+,	O
+the	O
+90th	O
+percentiles	O
+of	O
+PCDD	O
+/	O
+F	O
+releases	O
+for	O
+1999	O
+ranged	O
+up	O
+to	O
+4	O
+.	O
+1	O
+g	O
+I	O
+-	O
+TEQ	O
+/	O
+y	O
+.	O
+
+Gabapentin	O
+for	O
+opiod	O
+-	O
+related	O
+myoclonus	O
+in	O
+cancer	O
+patients	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Our	O
+meta	O
+-	O
+analysis	O
+of	O
+randomized	O
+controlled	O
+trials	O
+of	O
+HRT	O
+noted	O
+a	O
+statistically	O
+significant	O
+reduction	O
+in	O
+nonvertebral	O
+fractures	O
+.	O
+
+Newcastle	B-GENE
+disease	I-GENE
+antibody	I-GENE
+titre	O
+is	O
+dependent	O
+on	O
+serum	O
+calcium	O
+concentration	O
+.	O
+
+A	O
+total	O
+of	O
+25	O
+patients	O
+with	O
+malignant	O
+brain	O
+tumours	O
+were	O
+investigated	O
+.	O
+
+Net	O
+lift	O
+and	O
+combined	O
+drag	O
+from	O
+all	O
+8	O
+bearings	O
+of	O
+the	O
+4	O
+-	O
+bladed	O
+impeller	O
+are	O
+compared	O
+with	O
+predictions	O
+based	O
+on	O
+2	O
+-	O
+D	O
+theory	O
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+Gab1	B-GENE
+is	O
+involved	O
+in	O
+the	O
+control	O
+of	O
+egr	B-GENE
+-	I-GENE
+1	I-GENE
+expression	O
+regulated	O
+by	O
+insulin	B-GENE
+.	O
+
+The	O
+co	O
+-	O
+existence	O
+of	O
+TE	B-GENE
+domains	I-GENE
+within	O
+modular	O
+PKSs	B-GENE
+along	O
+with	O
+physically	O
+separated	O
+,	O
+monofunctional	O
+TEs	B-GENE
+(	O
+TE	B-GENE
+IIs	I-GENE
+)	O
+has	O
+been	O
+reported	O
+for	O
+a	O
+number	O
+of	O
+modular	O
+polyketide	O
+and	O
+non	B-GENE
+-	I-GENE
+ribosomal	I-GENE
+peptide	I-GENE
+synthases	I-GENE
+(	O
+NRPS	B-GENE
+)	O
+.	O
+
+To	O
+gain	O
+an	O
+understanding	O
+of	O
+the	O
+mGSTM2	B-GENE
+regulation	O
+,	O
+we	O
+have	O
+also	O
+cloned	O
+and	O
+analyzed	O
+its	O
+promoter	O
+region	O
+.	O
+
+10	O
+.	O
+0	O
++	O
+/	O
+-	O
+2	O
+.	O
+0	O
+pmol	O
+/	O
+24	O
+h	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+and	O
+remained	O
+elevated	O
+.	O
+
+SELECTION	O
+CRITERIA	O
+:	O
+All	O
+randomised	O
+controlled	O
+trials	O
+comparing	O
+IUSs	O
+with	O
+other	O
+forms	O
+of	O
+reversible	O
+contraceptives	O
+and	O
+reporting	O
+on	O
+pre	O
+-	O
+determined	O
+outcomes	O
+in	O
+women	O
+of	O
+reproductive	O
+years	O
+.	O
+
+OBJECTIVES	O
+:	O
+The	O
+objective	O
+of	O
+this	O
+review	O
+was	O
+to	O
+compare	O
+the	O
+effectiveness	O
+,	O
+safety	O
+and	O
+acceptability	O
+of	O
+the	O
+diaphragm	O
+with	O
+and	O
+without	O
+spermicide	O
+.	O
+
+To	O
+test	O
+the	O
+hypothesis	O
+that	O
+these	O
+elements	O
+are	O
+required	O
+for	O
+promoter	O
+activity	O
+,	O
+we	O
+compared	O
+the	O
+reporter	O
+expression	O
+activity	O
+of	O
+segments	O
+containing	O
+mutations	O
+of	O
+these	O
+elements	O
+with	O
+activity	O
+of	O
+the	O
+parent	B-GENE
+Hlx	I-GENE
+promoter	I-GENE
+sequence	I-GENE
+.	O
+
+In	O
+all	O
+of	O
+these	O
+cases	O
+,	O
+expression	O
+of	O
+the	O
+implicated	O
+genes	O
+was	O
+absent	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Ketamine	O
+-	O
+induced	O
+dissociative	O
+anesthesia	O
+produces	O
+persistently	O
+elevated	O
+BIS	O
+index	O
+which	O
+is	O
+different	O
+from	O
+thiamylal	O
+and	O
+those	O
+reported	O
+with	O
+other	O
+conventional	O
+anesthetic	O
+agents	O
+.	O
+
+Our	O
+results	O
+are	O
+reassuring	O
+and	O
+we	O
+therefore	O
+advise	O
+that	O
+in	O
+patients	O
+undergoing	O
+free	O
+jejunum	O
+flap	O
+reconstruction	O
+of	O
+the	O
+hypopharyngo	O
+-	O
+esophageal	O
+tract	O
+voice	O
+restoration	O
+should	O
+be	O
+attempted	O
+by	O
+placing	O
+a	O
+voice	O
+prosthesis	O
+through	O
+a	O
+secondary	O
+tracheo	O
+-	O
+esophageal	O
+puncture	O
+and	O
+providing	O
+intensive	O
+speech	O
+training	O
+.	O
+
+Hypercalcemia	O
+associated	O
+with	O
+elevated	O
+serum	B-GENE
+PTH	I-GENE
+concentration	O
+indicating	O
+primary	O
+hyperparathyroidism	O
+was	O
+found	O
+in	O
+7	O
+BC	O
+patients	O
+(	O
+7	O
+%	O
+)	O
+and	O
+in	O
+none	O
+of	O
+healthy	O
+women	O
+or	O
+patients	O
+with	O
+thyroid	O
+cancer	O
+.	O
+
+Positive	O
+and	O
+significant	O
+correlations	O
+were	O
+found	O
+between	O
+the	O
+weeks	O
+of	O
+pregnancy	O
+and	O
+Se	O
+levels	O
+in	O
+kidney	O
+(	O
+r	O
+=	O
+0	O
+.	O
+433	O
+,	O
+P	O
+=	O
+0	O
+.	O
+023	O
+)	O
+and	O
+heart	O
+(	O
+r	O
+=	O
+0	O
+.	O
+313	O
+,	O
+P	O
+=	O
+0	O
+.	O
+030	O
+)	O
+.	O
+
+This	O
+study	O
+suggests	O
+that	O
+PSP	O
+is	O
+more	O
+common	O
+than	O
+previously	O
+considered	O
+,	O
+is	O
+commonly	O
+misdiagnosed	O
+and	O
+that	O
+the	O
+majority	O
+of	O
+cases	O
+are	O
+not	O
+initially	O
+referred	O
+to	O
+neurologists	O
+.	O
+
+In	O
+Saccharomyces	O
+cerevisiae	O
+,	O
+entry	O
+into	O
+mitosis	O
+requires	O
+activation	O
+of	O
+the	O
+cyclin	B-GENE
+-	I-GENE
+dependent	I-GENE
+kinase	I-GENE
+Cdc28	B-GENE
+in	O
+its	O
+cyclin	B-GENE
+B	I-GENE
+(	O
+Clb	B-GENE
+)	O
+-	O
+associated	O
+form	O
+.	O
+
+We	O
+investigated	O
+the	O
+production	O
+of	O
+hyaluronan	O
+(	O
+HA	O
+)	O
+and	O
+its	O
+effect	O
+on	O
+cell	O
+motility	O
+in	O
+cells	O
+expressing	O
+the	O
+v	B-GENE
+-	I-GENE
+src	I-GENE
+mutants	I-GENE
+.	O
+
+Our	O
+results	O
+indicate	O
+that	O
+D	O
+(	O
+4	O
+)	O
+and	O
+D	O
+(	O
+2L	O
+)	O
+receptors	O
+activate	O
+the	O
+ERK	B-GENE
+kinase	I-GENE
+cascade	O
+by	O
+first	O
+mobilizing	O
+signaling	O
+by	O
+the	O
+PDGF	B-GENE
+receptor	I-GENE
+,	O
+followed	O
+by	O
+the	O
+subsequent	O
+activation	O
+of	O
+ERK1	B-GENE
+/	I-GENE
+2	I-GENE
+by	O
+pathways	O
+associated	O
+with	O
+this	O
+receptor	B-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+.	O
+
+Karger	O
+AG	O
+,	O
+Basel	O
+
+NIRS	O
+was	O
+used	O
+for	O
+the	O
+quantitative	O
+measurement	O
+of	O
+muscle	O
+O	O
+(	O
+2	O
+)	O
+consumption	O
+(	O
+mV	O
+.	O
+O	O
+(	O
+2	O
+)	O
+)	O
+and	O
+forearm	O
+blood	O
+flow	O
+(	O
+FBF	O
+)	O
+in	O
+78	O
+healthy	O
+subjects	O
+.	O
+
+No	O
+dominant	O
+clinical	O
+factor	O
+of	O
+risk	O
+was	O
+found	O
+,	O
+but	O
+multiple	O
+regression	O
+analysis	O
+identified	O
+age	O
+,	O
+body	O
+surface	O
+area	O
+,	O
+valve	O
+size	O
+,	O
+shop	O
+order	O
+fracture	O
+rate	O
+,	O
+and	O
+manufacturing	O
+period	O
+as	O
+risk	O
+factors	O
+for	O
+OSF	O
+.	O
+
+In	O
+this	O
+report	O
+this	O
+technique	O
+was	O
+applied	O
+to	O
+human	O
+breast	O
+carcinoma	O
+MDA	O
+-	O
+MB231	O
+cells	O
+overexpressing	O
+human	B-GENE
+MPG	I-GENE
+in	O
+order	O
+to	O
+assess	O
+whether	O
+up	O
+-	O
+regulation	O
+of	O
+the	O
+initial	O
+step	O
+in	O
+BER	O
+alters	O
+the	O
+activity	O
+of	O
+selected	O
+other	O
+BER	O
+(	O
+hOGG1	B-GENE
+and	O
+APE	B-GENE
+/	O
+ref	B-GENE
+-	I-GENE
+1	I-GENE
+)	O
+or	O
+direct	O
+reversal	O
+(	O
+MGMT	B-GENE
+)	O
+repair	O
+activities	O
+.	O
+
+The	O
+selective	O
+alteration	O
+of	O
+the	O
+genome	O
+using	O
+Cre	B-GENE
+recombinase	I-GENE
+to	O
+target	O
+the	O
+rearrangement	O
+of	O
+genes	O
+flanked	O
+by	O
+LOX	B-GENE
+recognition	I-GENE
+sequences	I-GENE
+has	O
+required	O
+the	O
+use	O
+of	O
+two	O
+separate	O
+genetic	O
+constructs	O
+in	O
+trans	O
+,	O
+one	O
+containing	O
+cre	O
+and	O
+the	O
+other	O
+containing	O
+the	O
+gene	O
+of	O
+interest	O
+flanked	O
+by	O
+LOX	B-GENE
+sites	I-GENE
+.	O
+
+Influence	O
+of	O
+compression	O
+therapy	O
+on	O
+symptoms	O
+following	O
+soft	O
+tissue	O
+injury	O
+from	O
+maximal	O
+eccentric	O
+exercise	O
+.	O
+
+Keratoconjunctivitis	O
+sicca	O
+appears	O
+to	O
+be	O
+a	O
+common	O
+ocular	O
+complication	O
+and	O
+all	O
+children	O
+with	O
+JRA	O
+should	O
+be	O
+screened	O
+for	O
+it	O
+with	O
+a	O
+comprehensive	O
+battery	O
+of	O
+tests	O
+.	O
+
+STAT5A	B-GENE
+mutations	O
+in	O
+the	O
+Src	B-GENE
+homology	I-GENE
+2	I-GENE
+(	O
+SH2	B-GENE
+)	O
+and	O
+SH3	B-GENE
+domains	I-GENE
+did	O
+not	O
+alter	O
+the	O
+BTK	B-GENE
+-	O
+mediated	O
+tyrosine	O
+phosphorylation	O
+.	O
+
+In	O
+conclusion	O
+,	O
+primary	O
+chemotherapy	O
+based	O
+on	O
+high	O
+dose	O
+MTX	O
+and	O
+ara	O
+-	O
+C	O
+is	O
+highly	O
+efficient	O
+in	O
+PCNSL	O
+.	O
+
+Reovirus	O
+mRNAs	O
+are	O
+efficiently	O
+translated	O
+within	O
+host	O
+cells	O
+despite	O
+the	O
+absence	O
+of	O
+3	O
+'	O
+polyadenylated	O
+tails	O
+.	O
+
+Analyses	O
+revealed	O
+that	O
+scale	O
+matters	O
+above	O
+and	O
+beyond	O
+the	O
+effect	O
+of	O
+quadrat	O
+area	O
+.	O
+
+Myasthenia	O
+gravis	O
+is	O
+an	O
+autoimmune	O
+disease	O
+resulting	O
+from	O
+the	O
+production	O
+of	O
+antibodies	O
+against	O
+the	O
+ACh	B-GENE
+receptors	I-GENE
+of	O
+the	O
+neuromuscular	O
+synapse	O
+.	O
+
+Copyright	O
+2001	O
+Academic	O
+Press	O
+.	O
+
+Using	O
+the	O
+postural	O
+and	O
+force	O
+data	O
+as	O
+input	O
+to	O
+a	O
+3	O
+-	O
+D	O
+biomechanical	O
+model	O
+,	O
+the	O
+lumbosacral	O
+spinal	O
+compression	O
+was	O
+calculated	O
+.	O
+
+Angina	O
+(	O
+Q	O
+)	O
+persistence	O
+showed	O
+marked	O
+associations	O
+with	O
+previous	O
+myocardial	O
+infarction	O
+,	O
+diagnosed	O
+angina	O
+,	O
+electrocardiogram	O
+ischemia	O
+,	O
+and	O
+subsequent	O
+major	O
+ischemic	O
+heart	O
+disease	O
+events	O
+from	O
+Q5	O
+onward	O
+.	O
+
+In	O
+the	O
+past	O
+decade	O
+,	O
+there	O
+have	O
+been	O
+enormous	O
+advances	O
+in	O
+the	O
+use	O
+of	O
+Bayesian	O
+methodology	O
+for	O
+analysis	O
+of	O
+epidemiologic	O
+data	O
+,	O
+and	O
+there	O
+are	O
+now	O
+many	O
+practical	O
+advantages	O
+to	O
+the	O
+Bayesian	O
+approach	O
+.	O
+
+To	O
+assess	O
+more	O
+specific	O
+PKA	B-GENE
+-	O
+dependent	O
+mediation	O
+of	O
+LH	B-GENE
+'	I-GENE
+s	I-GENE
+contribution	O
+to	O
+combined	O
+hormonal	O
+drive	O
+,	O
+the	O
+LDL	B-GENE
+receptor	I-GENE
+(	I-GENE
+-	I-GENE
+1076	I-GENE
+to	I-GENE
++	I-GENE
+11	I-GENE
+bp	I-GENE
+)	I-GENE
+reporter	I-GENE
+plasmid	O
+was	O
+cotransfected	O
+with	O
+a	O
+full	B-GENE
+-	I-GENE
+sequence	I-GENE
+rabbit	I-GENE
+muscle	I-GENE
+protein	I-GENE
+kinase	I-GENE
+inhibitor	I-GENE
+(	O
+PKI	B-GENE
+)	O
+minigene	O
+driven	O
+constitutively	O
+by	O
+a	O
+Rous	B-GENE
+sarcoma	I-GENE
+virus	I-GENE
+promoter	I-GENE
+.	O
+
+To	O
+investigate	O
+the	O
+convergent	O
+role	O
+of	O
+the	O
+insulin	B-GENE
+/	O
+IGF	B-GENE
+-	I-GENE
+I	I-GENE
+effector	O
+pathway	O
+mediating	O
+bihormonal	O
+stimulation	O
+of	O
+LDL	B-GENE
+receptor	I-GENE
+promoter	I-GENE
+expression	O
+,	O
+transfected	O
+granulosa	O
+-	O
+luteal	O
+cells	O
+were	O
+pretreated	O
+for	O
+30	O
+min	O
+with	O
+two	O
+specific	O
+inhibitors	O
+of	O
+phophatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+,	O
+wortmannin	O
+(	O
+100	O
+nM	O
+)	O
+and	O
+LY	O
+294002	O
+(	O
+10	O
+microM	O
+)	O
+,	O
+or	O
+of	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+kinase	I-GENE
+,	O
+PD	O
+98059	O
+(	O
+50	O
+microM	O
+)	O
+,	O
+U0126	O
+(	O
+10	O
+microM	O
+)	O
+,	O
+or	O
+the	O
+latter	O
+'	O
+s	O
+inactive	O
+derivative	O
+,	O
+U0124	O
+(	O
+10	O
+microM	O
+)	O
+.	O
+
+Concerted	O
+transcriptional	O
+activation	O
+of	O
+the	O
+low	B-GENE
+density	I-GENE
+lipoprotein	I-GENE
+receptor	I-GENE
+gene	I-GENE
+by	O
+insulin	B-GENE
+and	O
+luteinizing	B-GENE
+hormone	I-GENE
+in	O
+cultured	O
+porcine	O
+granulosa	O
+-	O
+luteal	O
+cells	O
+:	O
+possible	O
+convergence	O
+of	O
+protein	B-GENE
+kinase	I-GENE
+a	I-GENE
+,	O
+phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+,	O
+and	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+signaling	O
+pathways	O
+.	O
+
+These	O
+studies	O
+demonstrate	O
+that	O
+site	O
+-	O
+specific	O
+recognition	O
+of	O
+the	O
+bxd	B-GENE
+PRE	I-GENE
+by	O
+d	O
+(	O
+GA	O
+)	O
+(	O
+n	O
+)	O
+repeat	O
+binding	O
+activities	O
+mediates	O
+PcG	B-GENE
+-	O
+dependent	O
+silencing	O
+.	O
+
+Our	O
+findings	O
+further	O
+our	O
+understanding	O
+of	O
+how	O
+ZBP	B-GENE
+-	I-GENE
+89	I-GENE
+modulates	O
+cell	O
+proliferation	O
+and	O
+reveals	O
+a	O
+novel	O
+mechanism	O
+by	O
+which	O
+the	O
+p53	B-GENE
+protein	I-GENE
+is	O
+stabilized	O
+.	O
+
+A	O
+computerized	O
+method	O
+of	O
+determining	O
+the	O
+focal	O
+point	O
+of	O
+electrical	O
+activity	O
+in	O
+the	O
+pallidum	O
+of	O
+parkinsonian	O
+patients	O
+was	O
+developed	O
+using	O
+on	O
+-	O
+line	O
+quantitative	O
+physiological	O
+data	O
+analysis	O
+.	O
+
+Isolated	O
+Systolic	O
+Hypertension	O
+:	O
+An	O
+Update	O
+.	O
+
+The	O
+N	O
+-	O
+terminal	O
+portion	O
+of	O
+Notch	B-GENE
+(	I-GENE
+IC	I-GENE
+)	I-GENE
+inhibited	O
+p50	B-GENE
+DNA	O
+binding	O
+and	O
+interacted	O
+specifically	O
+with	O
+p50	B-GENE
+subunit	I-GENE
+,	O
+not	O
+p65	B-GENE
+of	O
+NF	B-GENE
+-	I-GENE
+kappaB	I-GENE
+.	O
+
+Conformational	O
+changes	O
+of	O
+the	O
+ferric	B-GENE
+uptake	I-GENE
+regulation	I-GENE
+protein	I-GENE
+upon	O
+metal	O
+activation	O
+and	O
+DNA	O
+binding	O
+;	O
+first	O
+evidence	O
+of	O
+structural	O
+homologies	O
+with	O
+the	O
+diphtheria	B-GENE
+toxin	I-GENE
+repressor	I-GENE
+.	O
+
+As	O
+a	O
+complement	O
+to	O
+genome	O
+-	O
+wide	O
+mapping	O
+and	O
+sequencing	O
+efforts	O
+,	O
+it	O
+is	O
+often	O
+important	O
+to	O
+generate	O
+detailed	O
+maps	O
+and	O
+sequence	O
+data	O
+for	O
+specific	O
+regions	O
+of	O
+interest	O
+.	O
+
+Granulocyte	B-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+(	O
+G	B-GENE
+-	I-GENE
+CSF	I-GENE
+)	O
+administration	O
+in	O
+vivo	O
+has	O
+been	O
+shown	O
+to	O
+improve	O
+the	O
+defence	O
+mechanisms	O
+against	O
+infection	O
+by	O
+different	O
+microbes	O
+.	O
+
+Among	O
+individuals	O
+,	O
+however	O
+,	O
+changes	O
+were	O
+strongly	O
+correlated	O
+with	O
+ACR	O
+levels	O
+at	O
+baseline	O
+.	O
+
+Thus	O
+,	O
+the	O
+screen	O
+for	O
+toxic	O
+p53	B-GENE
+mutants	I-GENE
+in	O
+yeast	O
+can	O
+identify	O
+novel	O
+p53	B-GENE
+variants	O
+that	O
+may	O
+be	O
+useful	O
+in	O
+dissecting	O
+p53	B-GENE
+regulated	O
+cellular	O
+responses	O
+and	O
+in	O
+developing	O
+p53	B-GENE
+-	O
+based	O
+cancer	O
+therapies	O
+.	O
+
+This	O
+is	O
+necessary	O
+if	O
+psychiatric	O
+diagnoses	O
+are	O
+ultimately	O
+going	O
+to	O
+be	O
+refined	O
+and	O
+validated	O
+against	O
+biological	O
+criteria	O
+.	O
+
+Since	O
+the	O
+latter	O
+is	O
+very	O
+small	O
+for	O
+physiological	O
+flows	O
+,	O
+the	O
+result	O
+is	O
+that	O
+alpha	O
+<	O
+1	O
+even	O
+at	O
+relatively	O
+high	O
+values	O
+of	O
+the	O
+Reynolds	O
+number	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+for	O
+non	O
+-	O
+negligible	O
+inertia	O
+)	O
+and	O
+we	O
+validate	O
+our	O
+perturbation	O
+theory	O
+results	O
+by	O
+comparison	O
+with	O
+a	O
+numerical	O
+integration	O
+of	O
+the	O
+full	O
+model	O
+.	O
+
+Cells	O
+lacking	O
+p116	B-GENE
+exhibit	O
+a	O
+striking	O
+defect	O
+in	O
+the	O
+formation	O
+of	O
+these	O
+macropinocytic	O
+structures	O
+,	O
+a	O
+concomitant	O
+reduction	O
+in	O
+the	O
+rate	O
+of	O
+fluid	O
+phase	O
+pinocytosis	O
+,	O
+a	O
+significant	O
+decrease	O
+in	O
+the	O
+efficiency	O
+of	O
+chemotactic	O
+aggregation	O
+,	O
+and	O
+a	O
+decrease	O
+in	O
+cellular	O
+F	B-GENE
+-	I-GENE
+actin	I-GENE
+content	O
+.	O
+
+The	O
+validity	O
+of	O
+the	O
+FPS	O
+-	O
+R	O
+was	O
+further	O
+supported	O
+by	O
+strong	O
+positive	O
+correlations	O
+with	O
+the	O
+VAS	O
+(	O
+r	O
+=	O
+0	O
+.	O
+92	O
+,	O
+N	O
+=	O
+45	O
+)	O
+and	O
+the	O
+CAS	O
+(	O
+r	O
+=	O
+0	O
+.	O
+84	O
+,	O
+N	O
+=	O
+45	O
+)	O
+in	O
+this	O
+clinical	O
+sample	O
+.	O
+
+The	O
+susceptibility	O
+of	O
+Aspergillus	O
+fumigatus	O
+to	O
+mulundocandin	O
+,	O
+an	O
+echinocandin	O
+-	O
+like	O
+compound	O
+,	O
+and	O
+other	O
+antifungal	O
+agents	O
+was	O
+assessed	O
+by	O
+the	O
+National	O
+Committee	O
+for	O
+Clinical	O
+Laboratory	O
+Standards	O
+(	O
+NCCLS	O
+)	O
+M38	O
+-	O
+P	O
+method	O
+,	O
+a	O
+2	O
+,	O
+3	O
+-	O
+bis	O
+(	O
+2	O
+-	O
+methoxy	O
+-	O
+4	O
+-	O
+nitro	O
+-	O
+5	O
+-	O
+sulfophenyl	O
+)	O
+-	O
+5	O
+-	O
+[	O
+(	O
+phenyl	O
+-	O
+amino	O
+)	O
+carbonyl	O
+]	O
+-	O
+2H	O
+-	O
+tetrazolium	O
+hydroxide	O
+(	O
+XTT	O
+)	O
+-	O
+based	O
+colorimetric	O
+assay	O
+,	O
+and	O
+determination	O
+of	O
+morphologic	O
+alterations	O
+by	O
+microscopy	O
+.	O
+
+DESIGN	O
+:	O
+A	O
+retrospective	O
+chart	O
+review	O
+of	O
+9	O
+,	O
+322	O
+patients	O
+undergoing	O
+surgical	O
+procedures	O
+in	O
+the	O
+period	O
+January	O
+1993	O
+to	O
+December	O
+1998	O
+.	O
+
+Pulmonary	O
+vein	O
+varix	O
+in	O
+association	O
+with	O
+bilateral	O
+pulmonary	O
+vein	O
+stenosis	O
+.	O
+
+Biochemical	O
+experiments	O
+have	O
+shown	O
+that	O
+CopG	B-GENE
+co	O
+-	O
+operatively	O
+associates	O
+to	O
+its	O
+target	O
+DNA	O
+at	O
+low	O
+protein	O
+:	O
+DNA	O
+ratios	O
+,	O
+completely	O
+protecting	O
+four	O
+helical	O
+turns	O
+on	O
+the	O
+same	O
+face	O
+of	O
+the	O
+double	O
+helix	O
+in	O
+both	O
+directions	O
+from	O
+the	O
+inverted	O
+repeat	O
+that	O
+constitutes	O
+the	O
+CopG	B-GENE
+primary	O
+target	O
+.	O
+
+We	O
+demonstrated	O
+that	O
+,	O
+under	O
+serum	O
+-	O
+starved	O
+conditions	O
+,	O
+KMS	O
+-	O
+11	O
+and	O
+OPM	O
+-	O
+2	O
+cells	O
+express	O
+appreciable	O
+levels	O
+of	O
+phosphorylated	O
+FGFR3	B-GENE
+mutants	I-GENE
+indicating	O
+a	O
+constitutive	O
+activation	O
+of	O
+the	O
+Y373C	B-GENE
+and	I-GENE
+K650E	I-GENE
+receptors	I-GENE
+;	O
+the	O
+addition	O
+of	O
+the	O
+aFGF	B-GENE
+ligand	I-GENE
+further	O
+increased	O
+the	O
+level	O
+of	O
+receptor	O
+phosphorylation	O
+.	O
+
+[	O
+figure	O
+:	O
+see	O
+text	O
+]	O
+The	O
+Stille	O
+coupling	O
+reaction	O
+has	O
+been	O
+performed	O
+in	O
+1	O
+-	O
+butyl	O
+-	O
+3	O
+-	O
+methylimidazolium	O
+tetrafluoroborate	O
+(	O
+BMIM	O
+BF4	O
+)	O
+,	O
+a	O
+room	O
+-	O
+temperature	O
+ionic	O
+liquid	O
+(	O
+RTIL	O
+)	O
+.	O
+
+Special	O
+issues	O
+devoted	O
+to	O
+the	O
+biosynthesis	O
+of	O
+woody	O
+plant	O
+biopolymers	O
+and	O
+related	O
+substances	O
+.	O
+
+Interactions	O
+between	O
+the	O
+checkpoint	O
+abrogator	O
+UCN	O
+-	O
+01	O
+and	O
+several	O
+pharmacological	O
+inhibitors	O
+of	O
+the	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	I-GENE
+MAPK	I-GENE
+)	I-GENE
+kinase	I-GENE
+(	O
+MEK	B-GENE
+)	O
+/	O
+MAPK	B-GENE
+pathway	O
+have	O
+been	O
+examined	O
+in	O
+a	O
+variety	O
+of	O
+human	O
+leukemia	O
+cell	O
+lines	O
+.	O
+
+Low	O
+affinity	O
+binding	O
+of	O
+Rab6A	B-GENE
+-	I-GENE
+GTP	I-GENE
+was	O
+also	O
+observed	O
+(	O
+K	O
+(	O
+d	O
+)	O
+=	O
+16	O
+microm	O
+)	O
+,	O
+whereas	O
+Rab1B	B-GENE
+,	I-GENE
+-	I-GENE
+5	I-GENE
+,	I-GENE
+-	I-GENE
+7	I-GENE
+,	I-GENE
+-	I-GENE
+8	I-GENE
+,	I-GENE
+or	I-GENE
+-	I-GENE
+11A	I-GENE
+did	O
+not	O
+bind	O
+.	O
+
+The	O
+students	O
+who	O
+had	O
+abnormal	O
+urine	O
+screening	O
+results	O
+at	O
+the	O
+first	O
+time	O
+received	O
+a	O
+second	O
+urine	O
+analysis	O
+10	O
+to	O
+15	O
+days	O
+later	O
+to	O
+confirm	O
+the	O
+abnormal	O
+urine	O
+analysis	O
+.	O
+
+Regulation	O
+of	O
+laminin	B-GENE
+beta2	I-GENE
+chain	I-GENE
+gene	I-GENE
+expression	O
+in	O
+human	O
+cancer	O
+cell	O
+lines	O
+.	O
+
+Northern	O
+and	O
+Western	O
+blot	O
+analyses	O
+demonstrated	O
+that	O
+Graf2	B-GENE
+is	O
+expressed	O
+in	O
+several	O
+tissues	O
+,	O
+with	O
+the	O
+highest	O
+expression	O
+in	O
+skeletal	O
+muscle	O
+.	O
+
+However	O
+,	O
+when	O
+directed	O
+to	O
+the	O
+nucleosome	O
+by	O
+fusion	O
+to	O
+core	B-GENE
+histone	I-GENE
+H2A	I-GENE
+or	O
+H2B	B-GENE
+,	O
+the	O
+non	O
+-	O
+histone	B-GENE
+tail	O
+forms	O
+an	O
+MCB	O
+that	O
+appears	O
+identical	O
+to	O
+that	O
+of	O
+the	O
+endogenous	O
+protein	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+proper	O
+direct	O
+binding	O
+of	O
+Nhp2p	B-GENE
+to	O
+H	B-GENE
+/	I-GENE
+ACA	I-GENE
+snoRNAs	I-GENE
+is	O
+required	O
+for	O
+the	O
+assembly	O
+of	O
+H	B-GENE
+/	I-GENE
+ACA	I-GENE
+snoRNPs	I-GENE
+and	O
+hence	O
+for	O
+the	O
+stability	O
+of	O
+some	O
+of	O
+their	O
+components	O
+.	O
+
+Telomerase	B-GENE
+is	O
+a	O
+ribonucleoprotein	O
+complex	O
+that	O
+synthesizes	O
+telomeric	O
+DNA	O
+onto	O
+chromosomes	O
+using	O
+its	O
+RNA	O
+component	O
+as	O
+template	O
+.	O
+
+SIT	B-GENE
+(	O
+SHP2	B-GENE
+-	I-GENE
+interacting	I-GENE
+transmembrane	I-GENE
+adaptor	I-GENE
+protein	I-GENE
+)	O
+is	O
+a	O
+recently	O
+identified	O
+transmembrane	O
+adaptor	O
+protein	O
+,	O
+which	O
+is	O
+expressed	O
+in	O
+lymphocytes	O
+.	O
+
+Ileal	O
+digestibilities	O
+of	O
+DM	O
+,	O
+OM	O
+,	O
+CP	O
+,	O
+total	O
+dietary	O
+fiber	O
+(	O
+TDF	O
+)	O
+,	O
+fat	O
+and	O
+gross	O
+energy	O
+(	O
+GE	O
+)	O
+were	O
+lower	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+for	O
+dogs	O
+fed	O
+diets	O
+containing	O
+supplemental	O
+fiber	O
+compared	O
+with	O
+dogs	O
+fed	O
+the	O
+control	O
+diet	O
+.	O
+
+Together	O
+these	O
+data	O
+imply	O
+that	O
+the	O
+HFV	B-GENE
+R	I-GENE
+region	I-GENE
+acts	O
+in	O
+the	O
+nucleus	O
+to	O
+modify	O
+the	O
+cytoplasmic	O
+fate	O
+of	O
+target	O
+HFV	O
+mRNA	O
+.	O
+
+These	O
+TxRE	B-GENE
+contain	O
+cyclic	O
+AMP	O
+-	O
+responsive	O
+elements	O
+(	O
+CRE	O
+)	O
+,	O
+but	O
+,	O
+remarkably	O
+,	O
+the	O
+"	O
+TGACGTCA	O
+"	O
+consensus	O
+is	O
+never	O
+strictly	O
+conserved	O
+in	O
+any	O
+viral	O
+strain	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+AGACGTCA	O
+,	O
+TGACGGCA	O
+,	O
+TGACCTCA	O
+)	O
+.	O
+
+And	O
+,	O
+most	O
+importantly	O
+,	O
+reconstitution	O
+of	O
+a	O
+consensus	O
+CRE	O
+,	O
+within	O
+the	O
+21	O
+-	O
+bp	O
+enhancers	O
+increases	O
+binding	O
+of	O
+CREB	B-GENE
+/	O
+ATF	B-GENE
+proteins	O
+but	O
+abrogates	O
+basal	O
+repression	O
+of	O
+LTR	O
+-	O
+directed	O
+transcription	O
+in	O
+vitro	O
+.	O
+
+Site	O
+-	O
+directed	O
+mutagenesis	O
+of	O
+CAR	B-GENE
+revealed	O
+that	O
+CAR	B-GENE
+residues	O
+Leu73	O
+and	O
+Lys121	O
+and	O
+/	O
+or	O
+Lys123	O
+are	O
+critical	O
+contact	O
+residues	O
+,	O
+with	O
+Tyr80	O
+and	O
+Tyr83	O
+being	O
+peripherally	O
+involved	O
+in	O
+the	O
+binding	O
+interaction	O
+with	O
+the	O
+Ad5	B-GENE
+,	I-GENE
+Ad9	I-GENE
+,	I-GENE
+Ad12	I-GENE
+,	I-GENE
+and	I-GENE
+Ad41L	I-GENE
+fiber	I-GENE
+knobs	I-GENE
+.	O
+
+This	O
+subfamily	O
+of	O
+genes	O
+all	O
+have	O
+a	O
+single	O
+ATP	O
+-	O
+binding	O
+domain	O
+at	O
+the	O
+N	O
+-	O
+terminus	O
+and	O
+a	O
+single	O
+C	O
+-	O
+terminal	O
+set	O
+of	O
+transmembrane	O
+segments	O
+.	O
+
+The	O
+promoter	O
+activity	O
+of	O
+the	O
+proximal	O
+region	O
+was	O
+found	O
+to	O
+be	O
+restricted	O
+to	O
+a	O
+subset	O
+of	O
+prestalk	O
+cells	O
+.	O
+
+Substitution	O
+of	O
+serine	O
+residues	O
+at	O
+the	O
+C	O
+-	O
+terminus	O
+indicated	O
+that	O
+loss	O
+of	O
+phosphorylation	O
+sites	O
+did	O
+not	O
+appear	O
+to	O
+have	O
+any	O
+effect	O
+on	O
+transcription	O
+and	O
+replication	O
+.	O
+
+Thus	O
+,	O
+replication	O
+fork	O
+movement	O
+near	O
+HML	B-GENE
+pauses	O
+at	O
+a	O
+silent	O
+origin	O
+which	O
+is	O
+competent	O
+for	O
+replication	O
+initiation	O
+but	O
+kept	O
+silent	O
+through	O
+Orc2p	B-GENE
+,	O
+a	O
+component	O
+of	O
+the	O
+replication	O
+initiator	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+the	O
+adapter	O
+Gab1	B-GENE
+may	O
+redirect	O
+c	B-GENE
+-	I-GENE
+Met	I-GENE
+signaling	O
+through	O
+PI3K	B-GENE
+away	O
+from	O
+a	O
+c	B-GENE
+-	I-GENE
+Akt	I-GENE
+/	O
+Pak1	B-GENE
+cell	O
+survival	O
+pathway	O
+.	O
+
+We	O
+have	O
+cloned	O
+a	O
+novel	O
+mouse	O
+protein	O
+,	O
+TAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+140	I-GENE
+,	O
+containing	O
+an	O
+HFD	B-GENE
+and	O
+a	O
+plant	B-GENE
+homeodomain	I-GENE
+(	O
+PHD	B-GENE
+)	O
+finger	O
+,	O
+which	O
+we	O
+demonstrated	O
+by	O
+immunoprecipitation	O
+to	O
+be	O
+a	O
+mammalian	B-GENE
+TFIID	I-GENE
+component	I-GENE
+.	O
+
+The	O
+other	O
+inhibitor	O
+was	O
+a	O
+single	O
+TAR	B-GENE
+decoy	O
+,	O
+driven	O
+by	O
+the	O
+U6	B-GENE
+small	I-GENE
+nuclear	I-GENE
+RNA	I-GENE
+promoter	I-GENE
+(	O
+U6	B-GENE
+-	I-GENE
+P	I-GENE
+)	O
+.	O
+
+In	O
+contrast	O
+to	O
+MPc3	B-GENE
+,	O
+data	O
+indicate	O
+that	O
+the	O
+Pc	B-GENE
+protein	I-GENE
+M33	B-GENE
+does	O
+not	O
+interact	O
+with	O
+AF9	B-GENE
+.	O
+
+Long	O
+-	O
+term	O
+results	O
+with	O
+MACOP	O
+-	O
+B	O
+and	O
+radiation	O
+therapy	O
+for	O
+aggressive	O
+lymphomas	O
+]	O
+BACKGROUND	O
+:	O
+Long	O
+-	O
+term	O
+results	O
+are	O
+needed	O
+to	O
+evaluate	O
+chemotherapy	O
+regimens	O
+and	O
+prognostic	O
+factors	O
+in	O
+non	O
+-	O
+Hodgkin	O
+'	O
+s	O
+lymphomas	O
+(	O
+NHL	O
+)	O
+.	O
+
+At	O
+20	O
+days	O
+(	O
+D	O
+)	O
+and	O
+at	O
+3	O
+months	O
+post	O
+-	O
+TBI	O
+,	O
+irradiated	O
+rats	O
+had	O
+a	O
+significantly	O
+lower	O
+percentage	O
+of	O
+avoidance	O
+than	O
+controls	O
+but	O
+no	O
+statistical	O
+difference	O
+was	O
+found	O
+at	O
+5	O
+months	O
+post	O
+-	O
+TBI	O
+.	O
+b	O
+/	O
+Two	O
+-	O
+way	O
+avoidance	O
+test	O
+:	O
+this	O
+test	O
+was	O
+performed	O
+only	O
+after	O
+TBI	O
+.	O
+
+At	O
+the	O
+end	O
+of	O
+each	O
+day	O
+of	O
+migration	O
+the	O
+pulmonary	O
+hemolymph	O
+PO2	O
+decreased	O
+by	O
+1	O
+-	O
+2	O
+.	O
+5	O
+kPa	O
+,	O
+but	O
+the	O
+hemocyanin	O
+remained	O
+saturated	O
+with	O
+O2	O
+and	O
+the	O
+venous	O
+reserve	O
+was	O
+largely	O
+unchanged	O
+(	O
+O2	O
+>	O
+0	O
+.	O
+4	O
+mmol	O
+x	O
+l	O
+(	O
+-	O
+1	O
+)	O
+)	O
+.	O
+
+DESIGN	O
+:	O
+Prospective	O
+cohort	O
+study	O
+with	O
+a	O
+20	O
+y	O
+follow	O
+-	O
+up	O
+period	O
+,	O
+the	O
+First	O
+National	O
+Health	O
+and	O
+Examination	O
+Survey	O
+(	O
+NHANES	O
+1	O
+)	O
+Epidemiologic	O
+Follow	O
+-	O
+up	O
+Study	O
+(	O
+NHEFS	O
+)	O
+.	O
+
+Mean	O
+Hg	O
+concentrations	O
+in	O
+the	O
+livers	O
+of	O
+mice	O
+at	O
+some	O
+sites	O
+in	O
+Isle	O
+Royale	O
+are	O
+not	O
+significantly	O
+lower	O
+(	O
+P	O
+=	O
+0	O
+.	O
+62	O
+)	O
+than	O
+Hg	O
+concentrations	O
+considered	O
+by	O
+some	O
+government	O
+agencies	O
+to	O
+be	O
+unhealthy	O
+for	O
+human	O
+consumption	O
+.	O
+
+There	O
+are	O
+many	O
+different	O
+proposals	O
+for	O
+the	O
+statistical	O
+analysis	O
+of	O
+data	O
+to	O
+determine	O
+early	O
+onset	O
+of	O
+action	O
+.	O
+
+The	O
+assay	O
+herein	O
+described	O
+allows	O
+the	O
+comparison	O
+of	O
+relative	O
+FGFR	B-GENE
+expression	O
+levels	O
+,	O
+both	O
+within	O
+a	O
+single	O
+RNA	O
+pool	O
+and	O
+among	O
+multiple	O
+RNA	O
+pool	O
+samples	O
+.	O
+
+The	O
+amount	O
+of	O
+drained	O
+effusion	O
+was	O
+measured	O
+,	O
+and	O
+fluid	O
+was	O
+sent	O
+for	O
+diagnostic	O
+assessment	O
+.	O
+
+The	O
+system	O
+,	O
+designed	O
+to	O
+exploit	O
+the	O
+relatively	O
+constant	O
+small	O
+intestine	O
+transit	O
+time	O
+,	O
+consists	O
+of	O
+a	O
+drug	O
+-	O
+containing	O
+core	O
+coated	O
+with	O
+a	O
+polymeric	O
+matrix	O
+formed	O
+by	O
+a	O
+channeling	O
+agent	O
+(	O
+NaCl	O
+,	O
+mannitol	O
+,	O
+and	O
+Emdex	O
+)	O
+and	O
+an	O
+inert	O
+polymer	O
+(	O
+Eudragit	O
+RS100	O
+)	O
+.	O
+
+STUDY	O
+OBJECTIVE	O
+:	O
+This	O
+study	O
+assessed	O
+several	O
+methodological	O
+aspects	O
+related	O
+to	O
+the	O
+quality	O
+of	O
+published	O
+controlled	O
+clinical	O
+trials	O
+(	O
+CCTs	O
+)	O
+in	O
+relation	O
+to	O
+the	O
+participation	O
+of	O
+an	O
+epidemiologist	O
+/	O
+biostatistician	O
+(	O
+E	O
+/	O
+B	O
+)	O
+.	O
+
+The	O
+median	O
+preoperative	O
+best	O
+-	O
+corrected	O
+visual	O
+acuity	O
+of	O
+0	O
+.	O
+08	O
+(	O
+range	O
+hand	O
+motions	O
+/	O
+0	O
+.	O
+003	O
+to	O
+0	O
+.	O
+4	O
+)	O
+,	O
+improved	O
+by	O
+5	O
+lines	O
+to	O
+a	O
+median	O
+final	O
+postoperative	O
+best	O
+-	O
+corrected	O
+visual	O
+acuity	O
+of	O
+0	O
+.	O
+25	O
+(	O
+range	O
+0	O
+.	O
+025	O
+-	O
+0	O
+.	O
+5	O
+)	O
+(	O
+P	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+A	O
+rare	O
+case	O
+of	O
+primary	O
+group	O
+A	O
+streptococcal	O
+peritonitis	O
+.	O
+
+Gimpl	O
+,	O
+F	O
+.	O
+
+BACKGROUND	O
+/	O
+AIMS	O
+:	O
+Hepatitis	O
+C	O
+and	O
+nonalcoholic	O
+fatty	O
+liver	O
+disease	O
+(	O
+NAFL	O
+)	O
+are	O
+the	O
+two	O
+most	O
+common	O
+forms	O
+of	O
+liver	O
+disease	O
+in	O
+the	O
+United	O
+States	O
+.	O
+
+Statistical	O
+Analysis	O
+included	O
+ANOVA	O
+,	O
+the	O
+Pearson	O
+Product	O
+Moment	O
+Correlation	O
+Coefficient	O
+,	O
+Principal	O
+Components	O
+Analysis	O
+and	O
+Discriminant	O
+Function	O
+Analysis	O
+and	O
+the	O
+calculation	O
+of	O
+Cronbach	O
+'	O
+s	O
+alpha	O
+(	O
+alpha	O
+)	O
+RESULTS	O
+:	O
+Both	O
+Sensitivity	O
+and	O
+specificity	O
+exceed	O
+90	O
+.	O
+00	O
+at	O
+23	O
+/	O
+24	O
+,	O
+Chronbach	O
+'	O
+s	O
+alpha	O
+for	O
+the	O
+total	O
+scale	O
+was	O
+equal	O
+to	O
+0	O
+.	O
+95	O
+.	O
+
+The	O
+titer	O
+of	O
+TSH	B-GENE
+binding	I-GENE
+inhibitor	I-GENE
+immunoglobulin	I-GENE
+(	O
+TBII	B-GENE
+)	O
+,	O
+which	O
+had	O
+been	O
+8	O
+.	O
+6	O
+%	O
+at	O
+initial	O
+presentation	O
+,	O
+rose	O
+to	O
+14	O
+.	O
+9	O
+%	O
+in	O
+2	O
+weeks	O
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+independent	O
+of	O
+uncertainties	O
+in	O
+the	O
+models	O
+,	O
+terrestrial	O
+planets	O
+with	O
+dense	O
+atmosphere	O
+like	O
+Venus	O
+can	O
+evolve	O
+into	O
+one	O
+of	O
+only	O
+four	O
+possible	O
+rotation	O
+states	O
+.	O
+
+Enantiomer	O
+separation	O
+of	O
+venlafaxine	O
+and	O
+O	O
+-	O
+desmethylvenlafaxine	O
+in	O
+human	O
+plasma	O
+.	O
+
+TE	O
+-	O
+671	O
+cells	O
+that	O
+were	O
+transfected	O
+with	O
+cAMP	O
+response	O
+element	O
+mutant	O
+constructs	O
+demonstrated	O
+a	O
+diminished	O
+basal	O
+activity	O
+of	O
+the	O
+GnRH	B-GENE
+-	I-GENE
+II	I-GENE
+promoter	I-GENE
+.	O
+
+They	O
+consist	O
+of	O
+at	O
+least	O
+two	O
+separable	O
+components	O
+,	O
+one	O
+heat	O
+stable	O
+and	O
+the	O
+other	O
+heat	O
+labile	O
+.	O
+
+Altogether	O
+,	O
+we	O
+confirm	O
+that	O
+all	O
+genes	O
+of	O
+the	O
+Rad52	B-GENE
+recombinational	O
+repair	O
+pathway	O
+are	O
+required	O
+for	O
+the	O
+survival	O
+of	O
+rad27	B-GENE
+Delta	I-GENE
+strains	O
+at	O
+both	O
+permissive	O
+(	O
+23	O
+degrees	O
+C	O
+)	O
+and	O
+semipermissive	O
+(	O
+30	O
+degrees	O
+C	O
+)	O
+temperatures	O
+for	O
+growth	O
+.	O
+
+In	O
+the	O
+last	O
+case	O
+,	O
+both	O
+hydroxychloroquine	O
+,	O
+carbamazepine	O
+and	O
+fluvoxamine	O
+had	O
+a	O
+common	O
+imputability	O
+which	O
+was	O
+plausible	O
+.	O
+
+We	O
+investigate	O
+the	O
+reaction	O
+kinetics	O
+of	O
+small	O
+spherical	O
+particles	O
+with	O
+inertia	O
+,	O
+obeying	O
+coalescence	O
+type	O
+of	O
+reaction	O
+,	O
+B	O
++	O
+B	O
+-	O
+-	O
+>	O
+B	O
+,	O
+and	O
+being	O
+advected	O
+by	O
+hydrodynamical	O
+flows	O
+with	O
+time	O
+-	O
+periodic	O
+forcing	O
+.	O
+
+The	O
+role	O
+of	O
+the	O
+Vp1	B-GENE
+DBD	I-GENE
+during	O
+infection	O
+was	O
+investigated	O
+by	O
+taking	O
+advantage	O
+of	O
+NLS	O
+phenotypic	O
+complementation	O
+(	O
+N	O
+.	O
+
+2	O
+were	O
+nonviable	O
+,	O
+and	O
+the	O
+mutant	B-GENE
+Vp1s	I-GENE
+unexpectedly	O
+failed	O
+to	O
+localize	O
+to	O
+the	O
+nucleus	O
+though	O
+Vp2	B-GENE
+and	O
+Vp3	B-GENE
+did	O
+,	O
+suggesting	O
+that	O
+the	O
+mutated	B-GENE
+NLS1	I-GENE
+acted	O
+as	O
+a	O
+dominant	O
+signal	O
+for	O
+the	O
+cytoplasmic	O
+localization	O
+of	O
+Vp1	B-GENE
+.	O
+
+Fasting	O
+gastrin	B-GENE
+levels	O
+(	O
+normal	O
+range	O
+:	O
+25	O
+-	O
+110	O
+mU	O
+/	O
+L	O
+)	O
+varied	O
+from	O
+48	O
+.	O
+78	O
+mU	O
+/	O
+L	O
+-	O
+168	O
+.	O
+20	O
+(	O
+mean	O
+:	O
+85	O
+.	O
+23	O
+mU	O
+/	O
+L	O
+)	O
+.	O
+
+Here	O
+,	O
+we	O
+show	O
+that	O
+the	O
+phorbol	O
+ester	O
+PMA	O
+decreases	O
+both	O
+basal	O
+and	O
+dexamethasone	O
+/	O
+cAMP	O
+-	O
+induced	O
+expression	O
+of	O
+a	O
+luciferase	B-GENE
+gene	I-GENE
+under	O
+the	O
+control	O
+of	O
+the	O
+G6Pase	B-GENE
+promoter	I-GENE
+in	O
+transiently	O
+transfected	O
+H4IIE	O
+hepatoma	O
+cells	O
+.	O
+
+Through	O
+deletion	O
+mutagenesis	O
+,	O
+we	O
+identify	O
+amino	O
+acids	O
+2003	O
+to	O
+2212	O
+of	O
+CBP	B-GENE
+,	O
+which	O
+we	O
+call	O
+carboxy	O
+-	O
+terminal	O
+region	O
+2	O
+(	O
+CR2	O
+)	O
+,	O
+as	O
+the	O
+minimal	O
+region	O
+for	O
+Tax	B-GENE
+interaction	O
+.	O
+
+Such	O
+knowledge	O
+could	O
+advance	O
+diagnosis	O
+and	O
+treatment	O
+of	O
+the	O
+patient	O
+and	O
+counseling	O
+of	O
+the	O
+affected	O
+family	O
+.	O
+
+BACKGROUND	O
+:	O
+There	O
+is	O
+increasing	O
+interest	O
+on	O
+the	O
+part	O
+of	O
+investigators	O
+and	O
+the	O
+public	O
+at	O
+large	O
+in	O
+finding	O
+ways	O
+to	O
+study	O
+and	O
+improve	O
+treatments	O
+for	O
+the	O
+seriously	O
+mentally	O
+ill	O
+without	O
+exposing	O
+such	O
+individuals	O
+to	O
+unnecessary	O
+risks	O
+.	O
+
+In	O
+the	O
+next	O
+week	O
+,	O
+the	O
+beta	O
+-	O
+adrenergic	O
+antagonist	O
+atenolol	O
+was	O
+added	O
+at	O
+an	O
+initial	O
+dose	O
+of	O
+25	O
+mg	O
+/	O
+day	O
+and	O
+titrated	O
+to	O
+50	O
+mg	O
+/	O
+day	O
+within	O
+1	O
+week	O
+.	O
+
+Lack	O
+of	O
+association	O
+between	O
+Kawasaki	O
+syndrome	O
+and	O
+infection	O
+with	O
+Rickettsia	O
+conorii	O
+,	O
+Rickettsia	O
+typhi	O
+,	O
+Coxiella	O
+burnetii	O
+or	O
+Ehrlichia	O
+phagocytophila	O
+group	O
+.	O
+
+The	O
+presence	O
+of	O
+AS	O
+-	O
+oligo	O
+had	O
+no	O
+further	O
+effect	O
+on	O
+the	O
+FSH	B-GENE
+-	O
+mediated	O
+activation	O
+of	O
+the	O
+EB	O
+*	O
+-	O
+mTf	B-GENE
+-	O
+CAT	B-GENE
+construct	O
+but	O
+reduced	O
+cAMP	O
+-	O
+mediated	O
+activation	O
+.	O
+
+This	O
+is	O
+a	O
+challenging	O
+task	O
+insofar	O
+as	O
+direct	O
+measures	O
+of	O
+ISF	O
+glucose	O
+are	O
+not	O
+readily	O
+available	O
+.	O
+
+We	O
+report	O
+the	O
+results	O
+of	O
+a	O
+detailed	O
+policy	O
+analysis	O
+comparing	O
+2	O
+CJD	O
+-	O
+related	O
+decisions	O
+:	O
+a	O
+1995	O
+recall	O
+of	O
+blood	O
+from	O
+a	O
+donor	O
+with	O
+classic	O
+CJD	O
+and	O
+the	O
+1999	O
+decision	O
+to	O
+defer	O
+donations	O
+from	O
+individuals	O
+with	O
+a	O
+6	O
+-	O
+month	O
+travel	O
+history	O
+to	O
+the	O
+UK	O
+between	O
+1980	O
+and	O
+1996	O
+due	O
+to	O
+concerns	O
+related	O
+to	O
+variant	O
+CJD	O
+.	O
+
+At	O
+visit	O
+5	O
+,	O
+the	O
+isokinetic	O
+test	O
+showed	O
+impaired	O
+muscle	O
+function	O
+recovery	O
+from	O
+23	O
+%	O
+to	O
+32	O
+%	O
+,	O
+while	O
+the	O
+manual	O
+test	O
+showed	O
+almost	O
+full	O
+recovery	O
+.	O
+
+We	O
+developed	O
+a	O
+system	O
+for	O
+domain	O
+shuffling	O
+to	O
+establish	O
+the	O
+function	O
+of	O
+C1	B-GENE
+domains	O
+from	O
+human	B-GENE
+Raf	I-GENE
+kinase	I-GENE
+and	O
+rat	B-GENE
+PKC	I-GENE
+eta	I-GENE
+in	O
+yeast	O
+.	O
+
+We	O
+interpret	O
+these	O
+data	O
+as	O
+further	O
+evidence	O
+that	O
+interaction	O
+with	O
+a	O
+small	B-GENE
+GTPase	I-GENE
+is	O
+the	O
+main	O
+regulatory	O
+function	O
+of	O
+the	O
+C1	B-GENE
+domain	O
+in	O
+yeast	O
+.	O
+
+Breast	O
+cancer	O
+risk	O
+assessment	O
+:	O
+Who	O
+holds	O
+the	O
+magic	O
+crystal	O
+ball	O
+?	O
+
+Patients	O
+with	O
+type	O
+III	O
+SOD	O
+may	O
+have	O
+visceral	O
+hyperalgesia	O
+;	O
+a	O
+trial	O
+of	O
+antidepressants	O
+or	O
+a	O
+therapeutic	O
+trial	O
+with	O
+botulinum	B-GENE
+toxin	I-GENE
+injection	O
+into	O
+the	O
+ampulla	O
+should	O
+be	O
+considered	O
+prior	O
+to	O
+more	O
+invasive	O
+endoscopic	O
+therapy	O
+.	O
+
+RESULTS	O
+:	O
+There	O
+is	O
+a	O
+considerable	O
+amount	O
+of	O
+variation	O
+between	O
+the	O
+results	O
+of	O
+TRA1	O
+and	O
+TRA2	O
+and	O
+between	O
+the	O
+results	O
+of	O
+both	O
+TRA	O
+'	O
+s	O
+and	O
+the	O
+door	O
+-	O
+to	O
+-	O
+door	O
+survey	O
+.	O
+
+In	O
+addition	O
+,	O
+these	O
+patients	O
+show	O
+both	O
+quantitative	O
+and	O
+qualitative	O
+differences	O
+in	O
+their	O
+infectious	O
+microbiological	O
+spectrum	O
+,	O
+mainly	O
+in	O
+clean	O
+-	O
+contaminated	O
+,	O
+contaminated	O
+and	O
+dirty	O
+surgical	O
+procedures	O
+.	O
+
+CONCLUSION	O
+:	O
+Extrusion	O
+cooking	O
+is	O
+effective	O
+for	O
+the	O
+inactivation	O
+of	O
+DON	O
+but	O
+is	O
+of	O
+limited	O
+value	O
+for	O
+AFB1	B-GENE
+,	O
+even	O
+if	O
+metabisulphite	O
+is	O
+added	O
+.	O
+
+The	O
+differences	O
+in	O
+the	O
+CPIgG	B-GENE
+,	O
+CRP	B-GENE
+,	O
+and	O
+fibrinogen	B-GENE
+levels	O
+in	O
+patients	O
+who	O
+were	O
+diagnosed	O
+with	O
+ACS	O
+versus	O
+those	O
+who	O
+were	O
+not	O
+(	O
+non	O
+-	O
+ACS	O
+)	O
+were	O
+evaluated	O
+.	O
+
+NaeI	B-GENE
+,	O
+a	O
+novel	O
+DNA	B-GENE
+endonuclease	I-GENE
+,	O
+shows	O
+topoisomerase	B-GENE
+and	O
+recombinase	B-GENE
+activities	O
+when	O
+a	O
+Lys	O
+residue	O
+is	O
+substituted	O
+for	O
+Leu	O
+43	O
+.	O
+
+The	O
+decrements	O
+in	O
+cerebrovascular	O
+resistance	O
+induced	O
+by	O
+hexamethonium	O
+,	O
+in	O
+mm	O
+Hg	O
+ml	O
+(	O
+-	O
+1	O
+)	O
+.	O
+min	O
+(	O
+-	O
+1	O
+)	O
+,	O
+were	O
+:	O
+under	O
+control	O
+.	O
+
+The	O
+desirability	O
+function	O
+is	O
+based	O
+on	O
+the	O
+search	O
+for	O
+a	O
+global	O
+optimum	O
+[	O
+D	O
+=	O
+f	O
+(	O
+Y1	O
+,	O
+Y2	O
+,	O
+.	O
+.	O
+.	O
+,	O
+Yn	O
+)	O
+]	O
+by	O
+the	O
+transformation	O
+of	O
+the	O
+measured	O
+property	O
+to	O
+a	O
+dimensionless	O
+scale	O
+for	O
+each	O
+criterion	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+vivo	O
+,	O
+there	O
+was	O
+a	O
+wide	O
+distribution	O
+with	O
+the	O
+coefficient	O
+of	O
+variation	O
+(	O
+SD	O
+/	O
+mean	O
+x	O
+100	O
+%	O
+)	O
+for	O
+different	O
+valve	O
+sizes	O
+ranging	O
+from	O
+21	O
+%	O
+to	O
+39	O
+%	O
+in	O
+the	O
+St	O
+Jude	O
+Medical	O
+valve	O
+and	O
+from	O
+25	O
+%	O
+to	O
+33	O
+%	O
+in	O
+the	O
+Omnicarbon	O
+valve	O
+.	O
+
+Even	O
+if	O
+the	O
+electrocardiographic	O
+signs	O
+are	O
+subdued	O
+,	O
+the	O
+underlying	O
+blockade	O
+of	O
+I	O
+(	O
+Kr	O
+)	O
+current	O
+may	O
+precipitate	O
+the	O
+occurrence	O
+of	O
+arrhythmia	O
+.	O
+
+The	O
+production	O
+of	O
+ceramide	O
+is	O
+emerging	O
+as	O
+a	O
+fixture	O
+of	O
+programmed	O
+cell	O
+death	O
+.	O
+
+We	O
+randomly	O
+assigned	O
+1	O
+,	O
+219	O
+subjects	O
+to	O
+receive	O
+either	O
+the	O
+standard	O
+three	O
+-	O
+times	O
+-	O
+weekly	O
+(	O
+TIW	O
+)	O
+interferon	B-GENE
+alfa	I-GENE
+-	I-GENE
+2b	I-GENE
+dose	O
+(	O
+3	O
+MIU	O
+)	O
+or	O
+the	O
+once	O
+-	O
+weekly	O
+(	O
+QW	O
+)	O
+peginterferon	B-GENE
+alfa	I-GENE
+-	I-GENE
+2b	I-GENE
+(	O
+0	O
+.	O
+5	O
+,	O
+1	O
+.	O
+0	O
+,	O
+or	O
+1	O
+.	O
+5	O
+microg	O
+/	O
+kg	O
+)	O
+.	O
+
+At	O
+cross	O
+purposes	O
+.	O
+
+Among	O
+the	O
+transcription	O
+factors	O
+known	O
+to	O
+interact	O
+with	O
+Groucho	B-GENE
+-	I-GENE
+related	I-GENE
+protein	I-GENE
+,	O
+only	O
+RUNX1	B-GENE
+was	O
+appreciably	O
+downregulated	O
+by	O
+E2A	B-GENE
+-	O
+HLF	B-GENE
+.	O
+
+The	O
+combination	O
+of	O
+ifosfamide	O
+,	O
+epirubicin	O
+and	O
+etoposide	O
+(	O
+IEV	O
+)	O
+is	O
+an	O
+effective	O
+salvage	O
+regimen	O
+for	O
+lymphoproliferative	O
+disease	O
+.	O
+
+A	O
+prospective	O
+trial	O
+was	O
+undertaken	O
+to	O
+determine	O
+(	O
+1	O
+)	O
+clinical	O
+characteristics	O
+of	O
+patients	O
+with	O
+chest	O
+pain	O
+;	O
+(	O
+2	O
+)	O
+value	O
+of	O
+cardiac	O
+markers	O
+troponin	B-GENE
+T	I-GENE
+,	O
+myoglobin	B-GENE
+and	O
+CK	B-GENE
+-	O
+MB	B-GENE
+mass	O
+in	O
+differentiating	O
+cardiac	O
+and	O
+noncardiac	O
+chest	O
+pain	O
+;	O
+(	O
+3	O
+)	O
+the	O
+proportion	O
+of	O
+patients	O
+with	O
+ACS	O
+in	O
+whom	O
+these	O
+markers	O
+provided	O
+helpful	O
+additional	O
+information	O
+on	O
+admission	O
+and	O
+afterwards	O
+.	O
+
+Cardiac	O
+markers	O
+troponin	B-GENE
+T	I-GENE
+,	O
+CK	B-GENE
+-	O
+MB	B-GENE
+mass	O
+and	O
+myoglobin	B-GENE
+were	O
+helpful	O
+in	O
+the	O
+differential	O
+diagnosis	O
+of	O
+chest	O
+pain	O
+,	O
+even	O
+when	O
+the	O
+ECG	O
+was	O
+unremarkable	O
+or	O
+nonspecific	O
+.	O
+
+At	O
+termination	O
+(	O
+gd	O
+20	O
+)	O
+,	O
+confirmed	O
+-	O
+pregnant	O
+females	O
+(	O
+21	O
+to	O
+25	O
+per	O
+group	O
+)	O
+were	O
+evaluated	O
+for	O
+clinical	O
+status	O
+and	O
+gestational	O
+outcome	O
+;	O
+live	O
+fetuses	O
+were	O
+examined	O
+for	O
+external	O
+,	O
+visceral	O
+,	O
+and	O
+skeletal	O
+malformations	O
+.	O
+
+One	O
+maternal	O
+death	O
+,	O
+reduced	O
+body	O
+weight	O
+,	O
+and	O
+reduced	O
+weight	O
+gain	O
+were	O
+noted	O
+at	O
+the	O
+high	O
+dose	O
+;	O
+confirmed	O
+pregnancy	O
+rates	O
+were	O
+84	O
+to	O
+100	O
+%	O
+for	O
+each	O
+group	O
+.	O
+
+In	O
+the	O
+further	O
+development	O
+of	O
+bladder	O
+neck	O
+suspension	O
+according	O
+to	O
+Stamey	O
+-	O
+Pereyra	O
+,	O
+the	O
+use	O
+of	O
+miniature	O
+bone	O
+anchors	O
+received	O
+considerable	O
+support	O
+.	O
+
+Simulating	O
+the	O
+impact	O
+during	O
+human	O
+jumping	O
+by	O
+means	O
+of	O
+a	O
+4	O
+-	O
+degrees	O
+-	O
+of	O
+-	O
+freedom	O
+model	O
+with	O
+time	O
+-	O
+dependent	O
+properties	O
+.	O
+
+A	O
+1	O
+-	O
+base	O
+pair	O
+mismatch	O
+within	O
+the	O
+corresponding	O
+region	O
+of	O
+the	O
+CYP3A4	B-GENE
+gene	I-GENE
+was	O
+sufficient	O
+for	O
+a	O
+differential	O
+enhancer	O
+activity	O
+.	O
+
+The	O
+authors	O
+made	O
+an	O
+analysis	O
+of	O
+social	O
+-	O
+economical	O
+conditions	O
+limiting	O
+the	O
+possibilities	O
+of	O
+rendering	O
+cardiosurgical	O
+care	O
+to	O
+children	O
+.	O
+
+METHODS	O
+:	O
+93	O
+female	O
+and	O
+43	O
+male	O
+patients	O
+undergoing	O
+thyroid	O
+surgery	O
+were	O
+stratified	O
+according	O
+to	O
+gender	O
+and	O
+then	O
+randomised	O
+to	O
+receive	O
+double	O
+-	O
+blind	O
+one	O
+of	O
+four	O
+antiemetic	O
+regimes	O
+:	O
+50	O
+mg	O
+dolasetron	O
+given	O
+orally	O
+45	O
+minutes	O
+prior	O
+to	O
+induction	O
+of	O
+anaesthesia	O
+(	O
+group	O
+I	O
+)	O
+,	O
+12	O
+.	O
+5	O
+mg	O
+dolasetron	O
+given	O
+intravenously	O
+during	O
+induction	O
+of	O
+anaesthesia	O
+(	O
+group	O
+II	O
+)	O
+,	O
+1	O
+.	O
+25	O
+mg	O
+DHB	B-GENE
+given	O
+intravenously	O
+during	O
+induction	O
+of	O
+anaesthesia	O
+(	O
+group	O
+III	O
+)	O
+or	O
+placebo	O
+(	O
+group	O
+IV	O
+)	O
+.	O
+
+This	O
+slow	O
+progression	O
+through	O
+the	O
+early	O
+G1	O
+-	O
+phase	O
+resulted	O
+in	O
+decreased	O
+phosphorylation	O
+of	O
+the	O
+RB	B-GENE
+protein	I-GENE
+and	O
+subsequent	O
+delay	O
+into	O
+the	O
+S	O
+phase	O
+transition	O
+.	O
+
+In	O
+mammals	O
+,	O
+the	O
+transcriptional	O
+repressors	O
+in	O
+the	O
+Wnt	B-GENE
+pathway	O
+are	O
+not	O
+well	O
+defined	O
+.	O
+
+Despite	O
+abundant	O
+expression	O
+of	O
+NtmybAS	B-GENE
+transcripts	I-GENE
+in	O
+mature	O
+pollen	O
+,	O
+gPAL1	B-GENE
+transcripts	I-GENE
+were	O
+not	O
+detectable	O
+in	O
+pollen	O
+.	O
+
+Identical	O
+effects	O
+were	O
+obtained	O
+when	O
+inhibitors	O
+and	O
+dominant	O
+negative	O
+mutants	O
+were	O
+tested	O
+on	O
+the	O
+-	O
+29	O
+to	O
++	O
+139	O
+bp	O
+region	O
+of	O
+the	O
+cyclin	B-GENE
+D1	I-GENE
+promoter	I-GENE
+.	O
+
+These	O
+findings	O
+suggest	O
+a	O
+novel	O
+ankyrin	B-GENE
+-	O
+independent	O
+role	O
+for	O
+LAD	B-GENE
+-	I-GENE
+1	I-GENE
+related	O
+to	O
+FGFR	B-GENE
+signaling	O
+.	O
+
+Moreover	O
+,	O
+elderly	O
+men	O
+with	O
+bioavailable	O
+estradiol	O
+levels	O
+below	O
+the	O
+median	O
+[	O
+40	O
+pmol	O
+/	O
+liter	O
+(	O
+11	O
+pg	O
+/	O
+ml	O
+)	O
+]	O
+had	O
+significantly	O
+higher	O
+rates	O
+of	O
+bone	O
+loss	O
+and	O
+levels	O
+of	O
+bone	O
+resorption	O
+markers	O
+than	O
+men	O
+with	O
+bioavailable	O
+estradiol	O
+levels	O
+above	O
+40	O
+pmol	O
+/	O
+liter	O
+.	O
+
+Competition	O
+electrophoretic	O
+mobility	O
+shift	O
+and	O
+immunoshift	O
+assays	O
+confirmed	O
+that	O
+NF1	B-GENE
+factors	I-GENE
+present	O
+in	O
+nuclear	O
+extracts	O
+of	O
+HeLa	O
+and	O
+CV	O
+-	O
+1	O
+cells	O
+bind	O
+to	O
+the	O
+BKV	B-GENE
+-	I-GENE
+MLP	I-GENE
+.	O
+
+This	O
+study	O
+demonstrates	O
+that	O
+inducible	O
+expression	O
+in	O
+response	O
+to	O
+either	O
+PMA	O
+or	O
+TPO	B-GENE
+is	O
+mediated	O
+through	O
+the	O
+Ets	B-GENE
+site	I-GENE
+in	O
+the	O
+proximal	O
+promoter	O
+of	O
+GPIX	B-GENE
+and	O
+is	O
+dependent	O
+upon	O
+the	O
+upstream	O
+activation	O
+of	O
+MAPK	B-GENE
+/	O
+extracellular	B-GENE
+signal	I-GENE
+-	I-GENE
+regulated	I-GENE
+kinase	I-GENE
+.	O
+
+RESULTS	O
+:	O
+The	O
+analyzed	O
+fragment	O
+has	O
+significant	O
+activity	O
+in	O
+EpCAM	B-GENE
+positive	O
+cells	O
+,	O
+and	O
+it	O
+is	O
+regulated	O
+negatively	O
+by	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+alpha	I-GENE
+(	O
+TNFalpha	B-GENE
+)	O
+.	O
+
+On	O
+Cox	O
+proportional	O
+hazards	O
+regression	O
+adenocarcinoma	O
+(	O
+P	O
+=	O
+0	O
+.	O
+006	O
+)	O
+,	O
+the	O
+development	O
+of	O
+BPF	O
+(	O
+P	O
+=	O
+0	O
+.	O
+003	O
+)	O
+,	O
+older	O
+age	O
+(	O
+P	O
+=	O
+0	O
+.	O
+03	O
+)	O
+and	O
+higher	O
+pathological	O
+stage	O
+(	O
+P	O
+=	O
+0	O
+.	O
+02	O
+)	O
+were	O
+independent	O
+adverse	O
+predictors	O
+of	O
+survival	O
+.	O
+
+Phosphatidylinositol	B-GENE
+3	I-GENE
+-	I-GENE
+kinase	I-GENE
+potentiates	O
+,	O
+but	O
+does	O
+not	O
+trigger	O
+,	O
+T	O
+cell	O
+proliferation	O
+mediated	O
+by	O
+the	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+receptor	I-GENE
+.	O
+
+In	O
+the	O
+stable	O
+transfectants	O
+(	O
+BM3	O
+cells	O
+)	O
+expressing	O
+a	O
+mutant	B-GENE
+bacterial	I-GENE
+P450	I-GENE
+AA	I-GENE
+epoxygenase	I-GENE
+,	O
+F87V	O
+BM3	O
+,	O
+which	O
+was	O
+genetically	O
+engineered	O
+to	O
+metabolize	O
+arachidonic	O
+acid	O
+only	O
+to	O
+14	O
+,	O
+15	O
+-	O
+EET	O
+,	O
+AA	O
+did	O
+not	O
+induce	O
+apoptosis	O
+and	O
+protected	O
+against	O
+agonist	O
+-	O
+induced	O
+apoptosis	O
+.	O
+
+The	O
+loop	O
+domain	O
+of	O
+heat	B-GENE
+shock	I-GENE
+transcription	I-GENE
+factor	I-GENE
+1	I-GENE
+dictates	O
+DNA	O
+-	O
+binding	O
+specificity	O
+and	O
+responses	O
+to	O
+heat	O
+stress	O
+.	O
+
+Progressive	O
+study	O
+and	O
+robustness	O
+test	O
+of	O
+QSAR	O
+model	O
+based	O
+on	O
+quantum	O
+chemical	O
+parameters	O
+for	O
+predicting	O
+BCF	O
+of	O
+selected	O
+polychlorinated	O
+organic	O
+compounds	O
+(	O
+PCOCs	O
+)	O
+.	O
+
+Of	O
+the	O
+six	O
+cases	O
+of	O
+malignant	O
+polyposis	O
+,	O
+none	O
+were	O
+identified	O
+using	O
+CT	O
+,	O
+and	O
+only	O
+two	O
+were	O
+diagnosed	O
+by	O
+small	O
+bowel	O
+follow	O
+-	O
+through	O
+.	O
+
+Using	O
+the	O
+two	O
+-	O
+hybrid	O
+system	O
+,	O
+we	O
+show	O
+that	O
+nonprenylated	O
+Rac1	B-GENE
+interacts	O
+very	O
+weakly	O
+with	O
+Rho	B-GENE
+-	I-GENE
+GDI	I-GENE
+,	O
+pointing	O
+to	O
+the	O
+predominant	O
+role	O
+of	O
+protein	O
+-	O
+isoprene	O
+interaction	O
+in	O
+complex	O
+formation	O
+.	O
+
+The	O
+patterns	O
+of	O
+early	O
+mRNA	O
+and	O
+protein	O
+expression	O
+in	O
+these	O
+seven	O
+mutants	O
+were	O
+examined	O
+,	O
+and	O
+it	O
+was	O
+found	O
+that	O
+mutation	O
+of	O
+the	O
+T	B-GENE
+'	I-GENE
+(	I-GENE
+135	I-GENE
+)	I-GENE
+acceptor	O
+site	O
+resulted	O
+in	O
+the	O
+utilization	O
+of	O
+cryptic	O
+splice	O
+sites	O
+and	O
+the	O
+generation	O
+of	O
+new	O
+T	B-GENE
+'	I-GENE
+species	O
+.	O
+
+Sixty	O
+-	O
+one	O
+cases	O
+of	O
+cholera	O
+,	O
+all	O
+caused	O
+by	O
+V	O
+.	O
+cholerae	O
+O1	O
+,	O
+were	O
+reported	O
+.	O
+
+Subsequently	O
+,	O
+these	O
+coordinates	O
+must	O
+be	O
+interpreted	O
+to	O
+define	O
+particular	O
+tissues	O
+and	O
+organs	O
+.	O
+
+Testing	O
+was	O
+associated	O
+with	O
+a	O
+history	O
+of	O
+nonsexual	O
+risk	O
+behavior	O
+,	O
+increased	O
+knowledge	O
+of	O
+the	O
+hepatitis	O
+C	O
+virus	O
+,	O
+and	O
+healthcare	O
+provider	O
+communication	O
+.	O
+
+Low	O
+-	O
+selenium	O
+diet	O
+has	O
+a	O
+human	O
+unfavourable	O
+impact	O
+.	O
+
+Thus	O
+,	O
+BALB	O
+/	O
+c	O
+mice	O
+appear	O
+to	O
+be	O
+the	O
+most	O
+appropriate	O
+strain	O
+of	O
+mice	O
+to	O
+perform	O
+studies	O
+on	O
+the	O
+possible	O
+connection	O
+between	O
+infection	O
+with	O
+T	O
+.	O
+canis	O
+and	O
+allergic	O
+asthma	O
+.	O
+
+Furthermore	O
+,	O
+hormonal	O
+regulation	O
+of	O
+G	O
+(	O
+1	O
+)	O
+gene	O
+transcription	O
+can	O
+occur	O
+even	O
+without	O
+additional	O
+activation	O
+of	O
+the	O
+Mek	B-GENE
+-	O
+Erk1	B-GENE
+/	I-GENE
+2	I-GENE
+pathway	O
+by	O
+estrogen	B-GENE
+receptors	I-GENE
+.	O
+
+Therefore	O
+,	O
+to	O
+understand	O
+how	O
+ErbB1	B-GENE
+/	O
+ErbB2	B-GENE
+signaling	O
+contributes	O
+to	O
+this	O
+process	O
+,	O
+we	O
+used	O
+the	O
+ErbB	B-GENE
+kinase	I-GENE
+inhibitor	O
+AG1478in	O
+ErbB2	B-GENE
+-	O
+dependent	O
+BT	O
+-	O
+474	O
+and	O
+SKBR	O
+-	O
+3	O
+human	O
+breast	O
+cancer	O
+cells	O
+.	O
+
+This	O
+plus	O
+the	O
+reduced	O
+phosphorylation	O
+of	O
+p27	B-GENE
+by	O
+MAPK	B-GENE
+enhanced	O
+the	O
+stability	O
+of	O
+p27	B-GENE
+that	O
+associated	O
+with	O
+nuclear	B-GENE
+Cdk2	I-GENE
+at	O
+high	O
+stoichiometry	O
+and	O
+inhibited	O
+its	O
+kinase	O
+activity	O
+.	O
+
+ICA	O
+in	O
+the	O
+reference	O
+solution	O
+was	O
+characterised	O
+by	O
+LC	O
+and	O
+time	O
+-	O
+of	O
+-	O
+flight	O
+(	O
+TOF	O
+)	O
+MS	O
+and	O
+quantified	O
+by	O
+LC	O
+chemiluminescent	O
+nitrogen	O
+detection	O
+(	O
+LC	O
+-	O
+CLND	O
+)	O
+.	O
+
+Forced	O
+expression	O
+of	O
+BZAP45	B-GENE
+strongly	O
+stimulates	O
+H4	B-GENE
+promoter	I-GENE
+(	O
+nt	O
+-	O
+215	O
+to	O
+-	O
+1	O
+)	O
+/	O
+CAT	B-GENE
+reporter	O
+gene	O
+activity	O
+.	O
+
+Local	O
+control	O
+rates	O
+were	O
+91	O
+%	O
+for	O
+metastatic	O
+lung	O
+cancer	O
+,	O
+89	O
+%	O
+for	O
+primary	O
+lung	O
+cancer	O
+and	O
+85	O
+%	O
+for	O
+T1	O
+,	O
+2N0M0	O
+cases	O
+.	O
+
+Utility	O
+of	O
+OAE	O
+screener	O
+(	O
+GSI	O
+70	O
+)	O
+for	O
+the	O
+evaluation	O
+of	O
+distortion	O
+product	O
+otoacoustic	O
+emissions	O
+]	O
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+the	O
+ability	O
+of	O
+the	O
+OAE	O
+screener	O
+GSI	O
+70	O
+to	O
+evaluate	O
+of	O
+cochlea	O
+function	O
+in	O
+neonates	O
+,	O
+infants	O
+and	O
+adults	O
+.	O
+
+For	O
+the	O
+sample	O
+of	O
+systematic	O
+reviews	O
+drawn	O
+from	O
+ACP	O
+Journal	O
+Club	O
+(	O
+n	O
+=	O
+103	O
+)	O
+,	O
+the	O
+PubMed	O
+strategy	O
+achieved	O
+a	O
+sensitivity	O
+of	O
+97	O
+%	O
+(	O
+CI	O
+,	O
+91	O
+%	O
+to	O
+99	O
+%	O
+)	O
+.	O
+
+Inhibition	O
+of	O
+JNK1	B-GENE
+and	O
+ERK	B-GENE
+kinase	O
+activities	O
+either	O
+by	O
+expression	O
+of	O
+the	O
+dominant	O
+negative	O
+mutant	O
+JNK1	B-GENE
+or	O
+by	O
+treatment	O
+with	O
+a	O
+selective	O
+chemical	O
+inhibitor	O
+of	O
+ERK	B-GENE
+(	O
+PD098059	O
+)	O
+substantially	O
+abrogates	O
+the	O
+UV	O
+induction	O
+of	O
+the	O
+GADD45	B-GENE
+promoter	I-GENE
+.	O
+
+With	O
+a	O
+GC	O
+content	O
+of	O
+45	O
+%	O
+the	O
+one	O
+segment	O
+would	O
+correspond	O
+to	O
+"	B-GENE
+isochore	I-GENE
+H1	I-GENE
+"	I-GENE
+and	O
+the	O
+other	O
+segment	O
+(	O
+39	O
+%	O
+GC	O
+in	O
+human	O
+,	O
+40	O
+%	O
+GC	O
+in	O
+mouse	O
+)	O
+to	O
+"	O
+isochore	O
+L1	B-GENE
+/	O
+L2	B-GENE
+"	O
+.	O
+
+No	O
+mutation	O
+of	O
+the	O
+NRL	B-GENE
+gene	I-GENE
+was	O
+found	O
+in	O
+any	O
+of	O
+the	O
+two	O
+families	O
+.	O
+
+After	O
+nerve	O
+injury	O
+,	O
+the	O
+nociceptive	O
+responses	O
+through	O
+type	O
+I	O
+neurons	O
+,	O
+which	O
+are	O
+polymodal	O
+C	O
+-	O
+fibers	O
+and	O
+drive	O
+NK1	B-GENE
+-	I-GENE
+receptor	I-GENE
+mechanisms	O
+in	O
+spinal	O
+pain	O
+transmission	O
+,	O
+were	O
+completely	O
+lost	O
+,	O
+but	O
+without	O
+changes	O
+in	O
+type	O
+II	O
+ones	O
+,	O
+which	O
+are	O
+polymodal	O
+C	O
+-	O
+fibers	O
+and	O
+drive	O
+NMDA	B-GENE
+receptor	I-GENE
+-	O
+mechanisms	O
+,	O
+while	O
+type	O
+III	O
+ones	O
+,	O
+which	O
+are	O
+capsaicin	O
+-	O
+insensitive	O
+(	O
+possibly	O
+A	O
+-	O
+fibers	O
+)	O
+and	O
+drive	O
+NMDA	B-GENE
+-	I-GENE
+receptor	I-GENE
+mechanisms	O
+,	O
+were	O
+markedly	O
+enhanced	O
+.	O
+
+This	O
+article	O
+reports	O
+the	O
+design	O
+and	O
+development	O
+of	O
+an	O
+ECG	O
+simulator	O
+intended	O
+for	O
+use	O
+in	O
+the	O
+testing	O
+,	O
+calibration	O
+and	O
+maintenance	O
+of	O
+electrocardiographic	O
+equipment	O
+.	O
+
+Subacute	O
+diencephalic	O
+angioencephalopathy	O
+(	O
+SDAE	O
+)	O
+is	O
+a	O
+rare	O
+and	O
+fatal	O
+disease	O
+of	O
+unknown	O
+etiology	O
+that	O
+involves	O
+the	O
+thalami	O
+bilaterally	O
+.	O
+
+Third	O
+,	O
+consistent	O
+with	O
+these	O
+data	O
+,	O
+N	O
+-	O
+acetylcysteine	O
+reduced	O
+the	O
+stimulatory	O
+effect	O
+of	O
+HGF	B-GENE
+on	O
+stress	B-GENE
+kinase	I-GENE
+activities	O
+,	O
+while	O
+p42	B-GENE
+/	I-GENE
+44	I-GENE
+mitogen	O
+activated	O
+kinase	O
+(	O
+MAPK	O
+)	O
+was	O
+unmodified	O
+,	O
+suggesting	O
+an	O
+involvement	O
+of	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+-	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinase	I-GENE
+(	O
+JNK	B-GENE
+)	O
+and	O
+p38	B-GENE
+MAPK	O
+in	O
+HIF	B-GENE
+-	I-GENE
+1	I-GENE
+activation	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
+difference	O
+in	O
+developmental	O
+scores	O
+at	O
+9	O
+or	O
+18	O
+months	O
+,	O
+although	O
+PDF	O
+infants	O
+had	O
+a	O
+2	O
+.	O
+8	O
+(	O
+-	O
+1	O
+.	O
+3	O
+-	O
+6	O
+.	O
+8	O
+)	O
+point	O
+advantage	O
+in	O
+Bayley	O
+motor	O
+score	O
+scales	O
+.	O
+
+In	O
+the	O
+single	O
+case	O
+the	O
+restoration	O
+of	O
+a	O
+structured	O
+daily	O
+routine	O
+represents	O
+the	O
+presupposition	O
+for	O
+a	O
+cognitive	O
+therapy	O
+.	O
+
+However	O
+these	O
+search	O
+engines	O
+respond	O
+with	O
+such	O
+cumbersome	O
+results	O
+that	O
+domain	O
+specific	O
+experts	O
+can	O
+not	O
+tolerate	O
+.	O
+
+The	O
+binary	O
+and	O
+tertiary	O
+combinations	O
+of	O
+plant	O
+-	O
+derived	O
+molluscicides	O
+Azadirachta	O
+indica	O
+and	O
+Cedrus	O
+deodara	O
+oil	O
+with	O
+synergists	O
+MGK	O
+-	O
+264	O
+,	O
+piperonyl	O
+butoxide	O
+(	O
+PB	O
+)	O
+and	O
+fruit	O
+powder	O
+of	O
+Embelia	O
+ribes	O
+were	O
+used	O
+against	O
+the	O
+Lymnaea	O
+acuminata	O
+.	O
+
+From	O
+the	O
+above	O
+results	O
+,	O
+we	O
+might	O
+infer	O
+that	O
+the	O
+seizure	O
+type	O
+of	O
+TLE	O
+and	O
+a	O
+high	O
+frequency	O
+of	O
+seizure	O
+are	O
+two	O
+major	O
+independent	O
+precipitate	O
+factors	O
+for	O
+abnormal	O
+latencies	O
+of	O
+P300	O
+in	O
+the	O
+epileptic	O
+patients	O
+.	O
+
+Audiological	O
+findings	O
+in	O
+pregnancy	O
+.	O
+
+The	O
+deubiquitinating	O
+enzyme	O
+DUB	B-GENE
+-	I-GENE
+2	I-GENE
+is	O
+induced	O
+in	O
+response	O
+to	O
+IL	B-GENE
+-	I-GENE
+2	I-GENE
+but	O
+as	O
+yet	O
+its	O
+function	O
+has	O
+not	O
+been	O
+determined	O
+.	O
+
+The	O
+isoform	O
+,	O
+designated	O
+HDAC9a	B-GENE
+,	O
+is	O
+132	O
+aa	O
+shorter	O
+at	O
+the	O
+C	O
+terminus	O
+than	O
+HDAC9	B-GENE
+.	O
+
+Pulmonary	O
+embolectomy	O
+and	O
+lung	O
+transplantation	O
+are	O
+the	O
+main	O
+indications	O
+for	O
+the	O
+use	O
+of	O
+heart	O
+-	O
+lung	O
+-	O
+machine	O
+.	O
+
+The	O
+NAUSICAA	O
+system	O
+gives	O
+a	O
+good	O
+knowledge	O
+of	O
+LET	O
+spectra	O
+for	O
+the	O
+first	O
+time	O
+in	O
+space	O
+dosimetry	O
+.	O
+
+In	O
+order	O
+to	O
+quantify	O
+these	O
+effects	O
+,	O
+tests	O
+were	O
+conducted	O
+in	O
+the	O
+NASA	O
+MSFC	O
+Neutral	O
+Buoyancy	O
+Simulator	O
+,	O
+in	O
+the	O
+NASA	O
+KC	O
+-	O
+135	O
+in	O
+parabolic	O
+flight	O
+,	O
+and	O
+in	O
+space	O
+with	O
+the	O
+EASE	O
+program	O
+during	O
+the	O
+Shuttle	O
+Atlantis	O
+mission	O
+61	O
+-	O
+B	O
+.	O
+
+This	O
+article	O
+comparatively	O
+evaluates	O
+five	O
+Generic	O
+Systems	O
+that	O
+describe	O
+the	O
+basic	O
+alternatives	O
+to	O
+composting	O
+facility	O
+design	O
+and	O
+control	O
+.	O
+
+Different	O
+thermoluminescent	O
+detectors	O
+(	O
+TLD	O
+)	O
+have	O
+been	O
+used	O
+to	O
+measure	O
+the	O
+contribution	O
+of	O
+the	O
+low	O
+linear	O
+energy	O
+transfer	O
+component	O
+(	O
+LET	O
+<	O
+10	O
+keV	O
+/	O
+micrometer	O
+)	O
+and	O
+plastic	O
+nuclear	O
+track	O
+detectors	O
+(	O
+PNTD	O
+)	O
+for	O
+the	O
+high	O
+linear	O
+energy	O
+tranfer	O
+(	O
+LET	O
+)	O
+component	O
+.	O
+
+Responses	O
+of	O
+TLD	O
+Mg2SiO4	O
+:	O
+Tb	O
+and	O
+radiophotoluminescent	O
+glass	O
+to	O
+heavy	O
+charged	O
+particles	O
+and	O
+space	O
+radiation	O
+.	O
+
+The	O
+absorbed	O
+dose	O
+was	O
+measured	O
+by	O
+combination	O
+of	O
+two	O
+integrating	O
+detectors	O
+:	O
+thermo	O
+-	O
+luminescent	O
+dosemeter	O
+of	O
+Mg2SiO4	O
+:	O
+Tb	O
+(	O
+TDMS	O
+)	O
+and	O
+plastic	O
+nuclear	O
+track	O
+detector	O
+(	O
+PNTD	O
+)	O
+.	O
+
+Thus	O
+,	O
+while	O
+the	O
+folds	O
+of	O
+all	O
+Myb	B-GENE
+domains	I-GENE
+resemble	O
+each	O
+other	O
+closely	O
+,	O
+the	O
+function	O
+of	O
+each	O
+Myb	B-GENE
+domain	I-GENE
+depends	O
+on	O
+the	O
+amino	O
+acid	O
+residues	O
+that	O
+are	O
+located	O
+on	O
+the	O
+surface	O
+of	O
+each	O
+protein	O
+.	O
+
+METHODS	O
+:	O
+Experiments	O
+testing	O
+the	O
+new	O
+catheter	O
+and	O
+comparing	O
+it	O
+to	O
+the	O
+existing	O
+catheter	O
+included	O
+:	O
+(	O
+1	O
+)	O
+measurement	O
+of	O
+the	O
+laser	O
+output	O
+beam	O
+sizes	O
+and	O
+divergences	O
+;	O
+(	O
+2	O
+)	O
+evaluation	O
+of	O
+particulate	O
+matter	O
+generation	O
+during	O
+ablation	O
+of	O
+atherosclerotic	O
+tissue	O
+;	O
+(	O
+3	O
+)	O
+measurement	O
+of	O
+ablation	O
+hole	O
+sizes	O
+and	O
+tissue	O
+penetration	O
+rates	O
+;	O
+(	O
+4	O
+)	O
+histopathologic	O
+examination	O
+of	O
+laser	O
+-	O
+induced	O
+in	O
+vivo	O
+vessel	O
+wall	O
+injury	O
+.	O
+
+Overexpression	O
+of	O
+RORgamma	B-GENE
+has	O
+been	O
+shown	O
+to	O
+inhibit	O
+T	B-GENE
+cell	I-GENE
+receptor	I-GENE
+-	O
+mediated	O
+apoptosis	O
+in	O
+T	O
+cell	O
+hybridomas	O
+and	O
+to	O
+repress	O
+the	O
+induction	O
+of	O
+Fas	B-GENE
+-	I-GENE
+ligand	I-GENE
+and	O
+interleukin	B-GENE
+2	I-GENE
+.	O
+
+Once	O
+ICP	O
+reaches	O
+critical	O
+values	O
+(	O
+>	O
+30	O
+mm	O
+Hg	O
+)	O
+herniation	O
+occurs	O
+,	O
+usually	O
+within	O
+2	O
+to	O
+5	O
+days	O
+.	O
+
+Other	O
+therapies	O
+are	O
+also	O
+available	O
+,	O
+including	O
+hypertonic	O
+saline	O
+solution	O
+,	O
+THAM	O
+(	O
+Tris	O
+-	O
+hydroxy	O
+-	O
+methyl	O
+-	O
+aminomethane	O
+)	O
+buffer	O
+,	O
+and	O
+high	O
+-	O
+dose	O
+barbiturates	O
+.	O
+
+CYP2C19	B-GENE
+genotype	I-GENE
+was	O
+determined	O
+by	O
+the	O
+polymerase	O
+chain	O
+reaction	O
+-	O
+restriction	O
+fragment	O
+length	O
+polymorphism	O
+method	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+a	O
+more	O
+differentiated	O
+diagnosis	O
+of	O
+the	O
+molar	O
+relationship	O
+will	O
+allow	O
+for	O
+a	O
+more	O
+causally	O
+directed	O
+correction	O
+of	O
+Class	O
+II	O
+molar	O
+relationship	O
+.	O
+
+Similar	O
+data	O
+were	O
+also	O
+obtained	O
+when	O
+either	O
+dominant	O
+negative	O
+EGFR	B-GENE
+-	O
+CD533	B-GENE
+or	O
+dominant	B-GENE
+negative	I-GENE
+Ras	I-GENE
+N17	I-GENE
+were	O
+used	O
+to	O
+block	O
+MAPK	B-GENE
+activation	O
+.	O
+
+These	O
+analyses	O
+re	O
+-	O
+open	O
+the	O
+question	O
+whether	O
+all	O
+the	O
+CesA	B-GENE
+genes	I-GENE
+encode	O
+cellulose	B-GENE
+synthases	I-GENE
+or	O
+whether	O
+some	O
+of	O
+the	O
+sub	O
+-	O
+class	O
+members	O
+may	O
+encode	O
+other	O
+non	B-GENE
+-	I-GENE
+cellulosic	I-GENE
+(	I-GENE
+1	I-GENE
+-	I-GENE
+-	I-GENE
+>	I-GENE
+4	I-GENE
+)	I-GENE
+beta	I-GENE
+-	I-GENE
+glycan	I-GENE
+synthases	I-GENE
+in	O
+plants	O
+.	O
+
+The	O
+mutation	O
+experiments	O
+showed	O
+that	O
+the	O
+most	O
+critical	O
+sequence	O
+for	O
+the	O
+repression	O
+of	O
+PTH	B-GENE
+was	O
+5	O
+'	O
+-	O
+GGGGGAGGGGAG	O
+-	O
+3	O
+'	O
+(	O
++	O
+1	O
+to	O
++	O
+12	O
+)	O
+of	O
+PTHSR	B-GENE
+.	O
+
+Cardiac	O
+output	O
+at	O
+anaerobic	O
+threshold	O
+(	O
+COAT	O
+)	O
+<	O
+or	O
+=	O
+7	O
+.	O
+3	O
+L	O
+/	O
+min	O
+was	O
+the	O
+best	O
+cutoff	O
+value	O
+for	O
+identifying	O
+multivessel	O
+coronary	O
+artery	O
+disease	O
+(	O
+relative	O
+risk	O
+,	O
+3	O
+.	O
+1	O
+)	O
+.	O
+
+Experience	O
+with	O
+xylene	O
+-	O
+free	O
+sections	O
+since	O
+1995	O
+at	O
+the	O
+Vrinnevi	O
+Hospital	O
+is	O
+favorable	O
+.	O
+
+A	O
+randomized	O
+mix	O
+of	O
+180	O
+sections	O
+(	O
+10	O
+samples	O
+x	O
+3	O
+tissues	O
+x	O
+3	O
+stains	O
+x	O
+2	O
+)	O
+gave	O
+90	O
+matched	O
+pairs	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+CYP71D20	B-GENE
+-	I-GENE
+encoded	I-GENE
+enzyme	I-GENE
+activity	O
+was	O
+capable	O
+of	O
+converting	O
+both	O
+5	O
+-	O
+epi	O
+-	O
+aristolochene	O
+and	O
+1	O
+-	O
+deoxycapsidiol	O
+to	O
+capsidiol	O
+in	O
+vitro	O
+,	O
+consistent	O
+with	O
+the	O
+notion	O
+that	O
+this	O
+P450	B-GENE
+enzyme	I-GENE
+catalyzes	O
+both	O
+hydroxylations	O
+of	O
+its	O
+hydrocarbon	O
+substrate	O
+.	O
+
+In	O
+conclusion	O
+,	O
+NF	B-GENE
+-	I-GENE
+Y	I-GENE
+and	O
+Sp1	B-GENE
+binding	O
+sites	O
+play	O
+a	O
+decisive	O
+role	O
+in	O
+the	O
+basal	O
+expression	O
+of	O
+the	O
+rat	B-GENE
+mrp2	I-GENE
+gene	I-GENE
+,	O
+while	O
+the	O
+human	B-GENE
+MRP2	I-GENE
+gene	I-GENE
+is	O
+regulated	O
+differently	O
+.	O
+
+Transcriptional	O
+regulation	O
+of	O
+the	O
+estrogen	O
+-	O
+inducible	O
+pS2	B-GENE
+breast	B-GENE
+cancer	I-GENE
+marker	I-GENE
+gene	I-GENE
+by	O
+the	O
+ERR	B-GENE
+family	I-GENE
+of	O
+orphan	B-GENE
+nuclear	I-GENE
+receptors	I-GENE
+.	O
+
+NB	O
+-	O
+506	O
+completely	O
+inhibits	O
+the	O
+capacity	O
+of	O
+topoisomerase	B-GENE
+I	I-GENE
+to	O
+phosphorylate	O
+,	O
+in	O
+vitro	O
+,	O
+the	O
+human	B-GENE
+splicing	I-GENE
+factor	I-GENE
+2	I-GENE
+/	O
+alternative	B-GENE
+splicing	I-GENE
+factor	I-GENE
+(	O
+SF2	B-GENE
+/	O
+ASF	B-GENE
+)	O
+.	O
+
+However	O
+,	O
+during	O
+our	O
+work	O
+with	O
+a	O
+replication	O
+-	O
+deficient	O
+virus	O
+expressing	O
+the	O
+ASF	B-GENE
+/	O
+SF2	B-GENE
+splicing	O
+factor	O
+from	O
+a	O
+progesterone	O
+antagonist	O
+-	O
+inducible	O
+gene	O
+cassette	O
+,	O
+we	O
+discovered	O
+that	O
+ASF	B-GENE
+/	O
+SF2	B-GENE
+was	O
+expressed	O
+at	O
+a	O
+significant	O
+level	O
+in	O
+the	O
+293	O
+producer	O
+cell	O
+line	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+inducer	O
+.	O
+
+DNA	O
+binding	O
+assays	O
+confirmed	O
+the	O
+interference	O
+of	O
+p30	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+with	O
+the	O
+assembly	O
+of	O
+CREB	B-GENE
+-	O
+Tax	B-GENE
+-	O
+p300	B-GENE
+/	O
+CBP	B-GENE
+multiprotein	O
+complexes	O
+on	O
+21	O
+-	O
+bp	O
+repeat	O
+oligonucleotides	O
+in	O
+vitro	O
+.	O
+
+Using	O
+the	O
+presented	O
+categorical	O
+structure	O
+as	O
+domain	O
+model	O
+a	O
+prototype	O
+DSS	O
+for	O
+dipslide	O
+urine	O
+cultures	O
+has	O
+been	O
+developed	O
+.	O
+
+DNA	O
+recognition	O
+by	O
+F	B-GENE
+factor	I-GENE
+TraI36	B-GENE
+:	O
+highly	O
+sequence	O
+-	O
+specific	O
+binding	O
+of	O
+single	O
+-	O
+stranded	O
+DNA	O
+.	O
+
+E47	B-GENE
+protein	I-GENE
+levels	O
+remain	O
+high	O
+until	O
+the	O
+double	O
+positive	O
+developmental	O
+stage	O
+,	O
+at	O
+which	O
+point	O
+they	O
+drop	O
+to	O
+relatively	O
+moderate	O
+levels	O
+,	O
+and	O
+are	O
+further	O
+downregulated	O
+upon	O
+transition	O
+to	O
+the	O
+single	O
+positive	O
+stage	O
+.	O
+
+The	O
+dual	O
+specificity	O
+kinases	O
+mitogen	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinase	I-GENE
+(	I-GENE
+MAPK	I-GENE
+)	I-GENE
+kinase	I-GENE
+(	I-GENE
+MKK	I-GENE
+)	I-GENE
+7	I-GENE
+and	O
+MKK4	B-GENE
+are	O
+the	O
+only	O
+molecules	O
+known	O
+to	O
+directly	O
+activate	O
+the	O
+stress	O
+kinases	O
+stress	B-GENE
+-	I-GENE
+activated	I-GENE
+protein	I-GENE
+kinases	I-GENE
+(	O
+SAPKs	B-GENE
+)	O
+/	O
+c	B-GENE
+-	I-GENE
+Jun	I-GENE
+N	I-GENE
+-	I-GENE
+terminal	I-GENE
+kinases	I-GENE
+(	O
+JNKs	B-GENE
+)	O
+in	O
+response	O
+to	O
+environmental	O
+or	O
+mitogenic	O
+stimuli	O
+.	O
+
+SAPK	B-GENE
+/	O
+JNK	B-GENE
+activation	O
+was	O
+completely	O
+abolished	O
+in	O
+the	O
+absence	O
+of	O
+MKK7	B-GENE
+,	O
+even	O
+though	O
+expression	O
+of	O
+MKK4	B-GENE
+was	O
+strongly	O
+upregulated	O
+in	O
+mkk7	B-GENE
+(	I-GENE
+-	I-GENE
+/	I-GENE
+-	I-GENE
+)	I-GENE
+mast	O
+cell	O
+lines	O
+,	O
+and	O
+phosphorylation	O
+of	O
+MKK4	B-GENE
+occurred	O
+normally	O
+in	O
+response	O
+to	O
+multiple	O
+stress	O
+stimuli	O
+.	O
+
+Thus	O
+,	O
+MKK7	B-GENE
+is	O
+an	O
+essential	O
+and	O
+specific	O
+regulator	O
+of	O
+stress	O
+-	O
+induced	O
+SAPK	B-GENE
+/	O
+JNK	B-GENE
+activation	O
+in	O
+mast	O
+cells	O
+and	O
+MKK7	B-GENE
+negatively	O
+regulates	O
+growth	O
+factor	O
+and	O
+antigen	O
+receptor	O
+-	O
+driven	O
+proliferation	O
+in	O
+hematopoietic	O
+cells	O
+.	O
+
+When	O
+mixed	O
+with	O
+aqueous	O
+solutions	O
+of	O
+TMT	O
+-	O
+55	O
+,	O
+aqueous	O
+solutions	O
+of	O
+either	O
+reagent	O
+-	O
+grade	O
+zinc	O
+,	O
+cadmium	O
+,	O
+or	O
+lead	O
+salts	O
+precipitate	O
+crystalline	O
+"	O
+Zn	O
+-	O
+TMT	O
+"	O
+,	O
+amorphous	O
+or	O
+crystalline	O
+"	O
+Cd	O
+-	O
+TMT	O
+"	O
+or	O
+amorphous	O
+"	O
+Pb	O
+-	O
+TMT	O
+"	O
+(	O
+M3	O
+[	O
+S3C3N3	O
+]	O
+2	O
+.	O
+nH2O	O
+,	O
+where	O
+M	O
+=	O
+Cd2	O
++	O
+,	O
+Pb2	O
++	O
+,	O
+and	O
+Zn2	O
++	O
+and	O
+n	O
+>	O
+or	O
+=	O
+0	O
+)	O
+that	O
+may	O
+eventually	O
+crystallize	O
+if	O
+stored	O
+in	O
+air	O
+.	O
+
+Many	O
+of	O
+the	O
+important	O
+genes	O
+associated	O
+with	O
+G1	O
+regulation	O
+have	O
+been	O
+shown	O
+to	O
+play	O
+a	O
+key	O
+role	O
+in	O
+proliferation	O
+,	O
+differentiation	O
+and	O
+oncogenic	O
+transformation	O
+and	O
+programmed	O
+cell	O
+death	O
+(	O
+apoptosis	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+the	O
+presence	O
+of	O
+TATA	O
+-	O
+unified	O
+transcription	O
+systems	O
+in	O
+contemporary	O
+eukaryotes	O
+and	O
+provide	O
+insight	O
+into	O
+the	O
+residual	O
+need	O
+for	O
+TBP	B-GENE
+by	O
+all	O
+three	O
+Pols	B-GENE
+in	O
+other	O
+eukaryotes	O
+despite	O
+a	O
+lack	O
+of	O
+TATA	O
+elements	O
+in	O
+their	O
+promoters	O
+.	O
+
+Thus	O
+,	O
+through	O
+a	O
+change	O
+in	O
+conformation	O
+upon	O
+repair	O
+of	O
+the	O
+6RG	O
+lesion	O
+,	O
+MGMT	B-GENE
+switches	O
+from	O
+a	O
+DNA	O
+repair	O
+factor	O
+to	O
+a	O
+transcription	O
+regulator	O
+(	O
+R	B-GENE
+-	I-GENE
+MGMT	I-GENE
+)	O
+,	O
+enabling	O
+the	O
+cell	O
+to	O
+sense	O
+as	O
+well	O
+as	O
+respond	O
+to	O
+mutagens	O
+.	O
+
+A	O
+split	O
+motor	O
+domain	O
+in	O
+a	O
+cytoplasmic	B-GENE
+dynein	I-GENE
+.	O
+
+In	O
+hypertensive	O
+nephrosclerosis	O
+,	O
+therapy	O
+containing	O
+an	O
+ACEI	O
+alone	O
+or	O
+in	O
+combination	O
+significantly	O
+reduces	O
+the	O
+incidence	O
+of	O
+renal	O
+events	O
+.	O
+
+Body	O
+weight	O
+reduction	O
+increases	O
+insulin	B-GENE
+sensitivity	O
+and	O
+improves	O
+both	O
+blood	O
+glucose	O
+and	O
+blood	O
+pressure	O
+control	O
+.	O
+
+Here	O
+we	O
+suggest	O
+that	O
+uvrA	B-GENE
+and	O
+the	O
+nucleotide	O
+excision	O
+repair	O
+pathway	O
+are	O
+involved	O
+in	O
+the	O
+repair	O
+of	O
+acid	O
+-	O
+induced	O
+DNA	O
+damage	O
+and	O
+are	O
+associated	O
+with	O
+successful	O
+adaptation	O
+of	O
+S	O
+.	O
+mutans	O
+to	O
+low	O
+pH	O
+.	O
+
+The	O
+best	O
+regression	O
+model	O
+for	O
+predicting	O
+changes	O
+in	O
+the	O
+WCXR	O
+included	O
+time	O
+to	O
+first	O
+positive	O
+culture	O
+and	O
+antibody	O
+titer	O
+for	O
+Pa	B-GENE
+elastase	I-GENE
+.	O
+
+Temperature	O
+measurement	O
+in	O
+microfluidic	O
+systems	O
+using	O
+a	O
+temperature	O
+-	O
+dependent	O
+fluorescent	O
+dye	O
+.	O
+
+APC	B-GENE
+-	O
+resistance	O
+was	O
+determined	O
+with	O
+a	O
+functional	O
+method	O
+with	O
+high	O
+sensitivity	O
+and	O
+specificity	O
+for	O
+the	O
+factor	B-GENE
+V	I-GENE
+Leiden	I-GENE
+mutation	I-GENE
+.	O
+
+Zarix	O
+expected	O
+patient	O
+enrollment	O
+in	O
+Canadian	O
+clinical	O
+sites	O
+to	O
+begin	O
+in	O
+Spring	O
+2001	O
+[	O
+397955	O
+]	O
+,	O
+[	O
+405928	O
+]	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+subjects	O
+in	O
+the	O
+augmented	O
+feedback	O
+group	O
+significantly	O
+reduced	O
+their	O
+peak	O
+vertical	O
+ground	O
+reaction	O
+force	O
+in	O
+both	O
+post	O
+-	O
+test	O
+conditions	O
+(	O
+2	O
+-	O
+minute	O
+post	O
+-	O
+test	O
+reduction	O
+,	O
+0	O
+.	O
+85	O
++	O
+/	O
+-	O
+0	O
+.	O
+62	O
+;	O
+1	O
+-	O
+week	O
+post	O
+-	O
+test	O
+reduction	O
+,	O
+0	O
+.	O
+74	O
++	O
+/	O
+-	O
+0	O
+.	O
+58	O
+)	O
+as	O
+compared	O
+to	O
+the	O
+sensory	O
+,	O
+control	O
+I	O
+,	O
+and	O
+control	O
+II	O
+feedback	O
+groups	O
+.	O
+
+Four	O
+casein	B-GENE
+kinase	I-GENE
+I	I-GENE
+isoforms	I-GENE
+are	O
+differentially	O
+partitioned	O
+between	O
+nucleus	O
+and	O
+cytoplasm	O
+.	O
+
+Use	O
+of	O
+a	O
+dual	O
+-	O
+pulse	O
+lithotripter	O
+to	O
+generate	O
+a	O
+localized	O
+and	O
+intensified	O
+cavitation	O
+field	O
+.	O
+
+When	O
+the	O
+blood	O
+clot	O
+is	O
+formed	O
+in	O
+the	O
+vitreous	O
+cavity	O
+,	O
+intravitreal	O
+injection	O
+of	O
+t	B-GENE
+-	I-GENE
+PA	I-GENE
+can	O
+convert	O
+plasminogen	B-GENE
+to	O
+plasmin	B-GENE
+and	O
+remove	O
+the	O
+clot	O
+.	O
+
+Management	O
+of	O
+postvitrectomy	O
+diabetic	O
+vitreous	O
+hemorrhage	O
+with	O
+tissue	B-GENE
+plasminogen	I-GENE
+activator	I-GENE
+(	O
+t	B-GENE
+-	I-GENE
+PA	I-GENE
+)	O
+and	O
+volume	O
+homeostatic	O
+fluid	O
+-	O
+fluid	O
+exchanger	O
+.	O
+
+Effect	O
+of	O
+heat	O
+treatments	O
+on	O
+the	O
+meltability	O
+of	O
+cheeses	O
+.	O
+
+RESULTS	O
+:	O
+Sixty	O
+per	O
+cent	O
+of	O
+African	O
+Americans	O
+exposed	O
+in	O
+26	O
+community	O
+outbreaks	O
+were	O
+TST	O
+positive	O
+compared	O
+to	O
+only	O
+40	O
+%	O
+of	O
+whites	O
+following	O
+comparable	O
+exposures	O
+.	O
+
+The	O
+mean	O
+waiting	O
+time	O
+to	O
+receive	O
+the	O
+pancreas	O
+transplant	O
+was	O
+244	O
+days	O
+for	O
+SPK	O
+and	O
+167	O
+days	O
+for	O
+PAK	O
+recipients	O
+(	O
+P	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Patients	O
+with	O
+antibody	O
+peaks	O
+,	O
+defined	O
+as	O
+fivefold	O
+or	O
+higher	O
+increase	O
+in	O
+antibody	O
+titer	O
+compared	O
+to	O
+the	O
+lowest	O
+antibody	O
+titer	O
+over	O
+the	O
+course	O
+of	O
+GBS	O
+,	O
+had	O
+higher	O
+disability	O
+scores	O
+during	O
+the	O
+first	O
+two	O
+weeks	O
+of	O
+GBS	O
+and	O
+a	O
+worse	O
+clinical	O
+outcome	O
+(	O
+anti	B-GENE
+-	I-GENE
+GM1	I-GENE
+IgG	I-GENE
+and	O
+anti	B-GENE
+-	I-GENE
+GD1a	I-GENE
+IgM	I-GENE
+antibody	I-GENE
+peaks	O
+)	O
+and	O
+axonal	O
+damage	O
+(	O
+anti	B-GENE
+-	I-GENE
+GD1a	I-GENE
+IgM	I-GENE
+antibody	I-GENE
+peaks	O
+)	O
+,	O
+compared	O
+to	O
+patients	O
+without	O
+peak	O
+antibody	O
+titers	O
+.	O
+
+Following	O
+baseline	O
+clinical	O
+examination	O
+and	O
+initial	O
+periodontal	O
+therapy	O
+,	O
+32	O
+patients	O
+received	O
+mucogingival	O
+surgery	O
+with	O
+free	O
+gingival	O
+grafts	O
+for	O
+treatment	O
+of	O
+insufficient	O
+attached	O
+gingiva	O
+.	O
+
+However	O
+,	O
+patients	O
+with	O
+isolated	O
+office	O
+hypertension	O
+had	O
+fewer	O
+previous	O
+cardiovascular	O
+complications	O
+.	O
+
+In	O
+the	O
+TVD	O
+-	O
+patients	O
+decreases	O
+in	O
+skin	O
+blood	O
+flow	O
+were	O
+similar	O
+compared	O
+with	O
+the	O
+healthy	O
+controls	O
+.	O
+
+2	O
+:	O
+The	O
+dynamic	O
+moduli	O
+of	O
+microcrystalline	O
+cellulose	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+an	O
+intracellular	O
+WT	B-GENE
+-	I-GENE
+1	I-GENE
+/	O
+HSAL2	B-GENE
+pathway	O
+may	O
+play	O
+a	O
+role	O
+in	O
+development	O
+and	O
+hematopoiesis	O
+.	O
+
+Phosphotyrosyl	O
+peptides	O
+block	O
+Stat3	B-GENE
+-	O
+mediated	O
+DNA	O
+binding	O
+activity	O
+,	O
+gene	O
+regulation	O
+,	O
+and	O
+cell	O
+transformation	O
+.	O
+
+Plane	O
+wave	O
+geometry	O
+is	O
+impractical	O
+for	O
+clinical	O
+use	O
+but	O
+the	O
+results	O
+of	O
+this	O
+work	O
+encouraged	O
+us	O
+to	O
+further	O
+develop	O
+the	O
+P3	O
+approximation	O
+for	O
+a	O
+spherical	O
+geometry	O
+,	O
+described	O
+in	O
+this	O
+paper	O
+.	O
+
+The	O
+diagnosis	O
+of	O
+HCV	O
+arthritis	O
+in	O
+patients	O
+with	O
+positive	O
+rheumatoid	B-GENE
+factor	I-GENE
+and	O
+chronic	O
+inflammatory	O
+polyarthritis	O
+may	O
+be	O
+difficult	O
+.	O
+
+METHODS	O
+:	O
+We	O
+retrospectively	O
+selected	O
+13	O
+TFCD	O
+patients	O
+who	O
+underwent	O
+surgery	O
+for	O
+intractable	O
+epilepsy	O
+with	O
+the	O
+aim	O
+of	O
+removing	O
+the	O
+magnetic	O
+resonance	O
+(	O
+MR	O
+)	O
+-	O
+detectable	O
+lesion	O
+and	O
+/	O
+or	O
+the	O
+epileptogenic	O
+zone	O
+defined	O
+by	O
+stereoelectroencephalographic	O
+recordings	O
+.	O
+
+RESULTS	O
+:	O
+At	O
+latest	O
+examination	O
+,	O
+mean	O
+UPDRS	O
+II	O
+and	O
+III	O
+scores	O
+had	O
+improved	O
+by	O
+30	O
+%	O
+(	O
+on	O
+stimulation	O
+,	O
+off	O
+therapy	O
+)	O
+with	O
+mean	O
+50	O
+%	O
+reduction	O
+in	O
+daily	O
+off	O
+time	O
+.	O
+
+In	O
+Exp	O
+.	O
+
+Several	O
+distinct	O
+apoptotic	O
+stimuli	O
+induce	O
+the	O
+expression	O
+and	O
+caspase	B-GENE
+-	O
+dependent	O
+cleavage	O
+of	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+80	I-GENE
+delta	I-GENE
+.	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+80	I-GENE
+delta	I-GENE
+,	O
+unlike	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+80	I-GENE
+,	O
+forms	O
+a	O
+TFIID	B-GENE
+-	I-GENE
+like	I-GENE
+complex	I-GENE
+lacking	O
+hTAF	B-GENE
+(	I-GENE
+II	I-GENE
+)	I-GENE
+31	I-GENE
+.	O
+
+Endovascular	O
+aneurysm	O
+repair	O
+with	O
+the	O
+AneuRx	O
+stent	O
+-	O
+graft	O
+is	O
+safe	O
+,	O
+but	O
+is	O
+it	O
+effective	O
+?	O
+
+Chronic	O
+nutritional	O
+diseases	O
+of	O
+infectious	O
+origin	O
+:	O
+an	O
+assessment	O
+of	O
+a	O
+nascent	O
+field	O
+.	O
+
+Drug	O
+interactions	O
+have	O
+been	O
+found	O
+with	O
+drugs	O
+that	O
+compete	O
+for	O
+the	O
+same	O
+CYP450	B-GENE
+isoenzymes	I-GENE
+as	O
+statins	O
+.	O
+
+METHODS	O
+:	O
+We	O
+studied	O
+the	O
+clinical	O
+benefit	O
+of	O
+depth	O
+-	O
+dependent	O
+RR	O
+,	O
+nonuniform	O
+AC	O
+using	O
+a	O
+scanning	O
+line	O
+source	O
+,	O
+and	O
+scatter	O
+correction	O
+(	O
+photon	O
+energy	O
+recovery	O
+[	O
+PER	O
+]	O
+)	O
+compared	O
+with	O
+filtered	O
+backprojection	O
+alone	O
+.	O
+
+Because	O
+of	O
+differences	O
+in	O
+patient	O
+characteristics	O
+,	O
+control	O
+measurements	O
+were	O
+obtained	O
+from	O
+normal	O
+muscle	O
+in	O
+all	O
+patients	O
+.	O
+
+However	O
+,	O
+the	O
+abi1	B-GENE
+-	I-GENE
+1	I-GENE
+gene	I-GENE
+product	I-GENE
+has	O
+no	O
+effect	O
+on	O
+the	O
+ABA	O
+suppression	O
+of	O
+a	O
+GA	O
+-	O
+responsive	O
+alpha	B-GENE
+-	I-GENE
+amylase	I-GENE
+gene	I-GENE
+.	O
+
+In	O
+children	O
+unable	O
+to	O
+perform	O
+forced	O
+expiratory	O
+maneuvers	O
+(	O
+n	O
+=	O
+25	O
+)	O
+,	O
+FOT	O
+,	O
+contrary	O
+to	O
+the	O
+interrupter	O
+technique	O
+,	O
+clearly	O
+identified	O
+a	O
+subgroup	O
+of	O
+young	O
+children	O
+with	O
+high	O
+resistance	O
+values	O
+at	O
+baseline	O
+,	O
+which	O
+returned	O
+to	O
+normal	O
+after	O
+bronchodilation	O
+.	O
+
+In	O
+budding	O
+yeast	O
+,	O
+this	O
+latter	O
+checkpoint	O
+response	O
+involves	O
+the	O
+proteins	O
+Mad1	B-GENE
+,	I-GENE
+2	I-GENE
+,	I-GENE
+3	I-GENE
+,	O
+Bub1	B-GENE
+and	O
+Bub3	B-GENE
+,	O
+whose	O
+vertebrate	O
+counterparts	O
+localize	O
+to	O
+unattached	O
+kinetochores	O
+.	O
+
+HTLV	O
+-	O
+1	O
+decreases	O
+Th2	O
+type	O
+of	O
+immune	O
+response	O
+in	O
+patients	O
+with	O
+strongyloidiasis	O
+.	O
+
+However	O
+,	O
+the	O
+beta5L	O
+splice	O
+variant	O
+was	O
+found	O
+only	O
+in	O
+the	O
+retina	O
+.	O
+
+PROCEDURE	O
+:	O
+Cannulas	O
+were	O
+surgically	O
+positioned	O
+in	O
+the	O
+abomasal	O
+body	O
+and	O
+pyloric	O
+antrum	O
+of	O
+each	O
+calf	O
+.	O
+
+METHODS	O
+:	O
+Humphrey	O
+Field	O
+Analyzer	O
+model	O
+630	O
+(	O
+HFA	O
+I	O
+,	O
+program	O
+30	O
+-	O
+2	O
+with	O
+a	O
+rectangular	O
+6	O
+degrees	O
+x	O
+6	O
+degrees	O
+grid	O
+)	O
+was	O
+used	O
+as	O
+the	O
+conventional	O
+perimetric	O
+method	O
+.	O
+
+Transforming	B-GENE
+growth	I-GENE
+factor	I-GENE
+-	I-GENE
+beta	I-GENE
+(	O
+TGF	B-GENE
+-	I-GENE
+beta	I-GENE
+)	O
+induced	O
+growth	O
+arrest	O
+of	O
+cells	O
+involves	O
+regulation	O
+of	O
+the	O
+activities	O
+of	O
+both	O
+D	B-GENE
+-	I-GENE
+and	I-GENE
+E	I-GENE
+-	I-GENE
+type	I-GENE
+cyclin	I-GENE
+kinase	I-GENE
+complexes	I-GENE
+thought	O
+to	O
+be	O
+mediated	O
+primarily	O
+by	O
+the	O
+regulation	O
+of	O
+p15	B-GENE
+(	O
+Ink4b	B-GENE
+)	O
+and	O
+p27	B-GENE
+(	O
+Kip1	B-GENE
+)	O
+cyclin	O
+kinase	O
+inhibitors	O
+.	O
+
+Alignment	O
+of	O
+different	O
+cDNAs	O
+of	O
+the	O
+NR5A2	B-GENE
+(	O
+hB1F	B-GENE
+)	O
+gene	O
+with	O
+the	O
+genomic	O
+sequence	O
+facilitated	O
+the	O
+delineation	O
+of	O
+its	O
+structural	O
+organization	O
+,	O
+which	O
+spans	O
+over	O
+150	O
+kb	O
+and	O
+consists	O
+of	O
+eight	O
+exons	O
+interrupted	O
+by	O
+seven	O
+introns	O
+.	O
+
+The	O
+genomic	O
+structure	O
+of	O
+the	O
+human	B-GENE
+SPEC1	I-GENE
+gene	I-GENE
+reveals	O
+complex	O
+splicing	O
+and	O
+close	O
+promoter	O
+proximity	O
+to	O
+the	O
+AF1q	B-GENE
+translocation	I-GENE
+gene	I-GENE
+.	O
+
+Hp	O
+positive	O
+relatives	O
+of	O
+gastric	O
+cancer	O
+had	O
+a	O
+markedly	O
+higher	O
+prevalence	O
+of	O
+atrophy	O
+than	O
+those	O
+with	O
+Hp	O
+negativity	O
+without	O
+cancer	O
+relatives	O
+(	O
+29	O
+vs	O
+.	O
+
+Peripheral	O
+metabolism	O
+of	O
+androgens	O
+takes	O
+place	O
+in	O
+various	O
+areas	O
+within	O
+the	O
+pilosebaceous	O
+unit	O
+,	O
+as	O
+indicated	O
+by	O
+local	O
+differences	O
+in	O
+the	O
+activities	O
+of	O
+aromatase	B-GENE
+,	O
+5alpha	B-GENE
+-	I-GENE
+reductase	I-GENE
+as	O
+well	O
+as	O
+of	O
+the	O
+presence	O
+of	O
+the	O
+androgen	B-GENE
+receptors	I-GENE
+.	O
+
+The	O
+uptake	O
+of	O
+fluorine	O
+-	O
+18	O
+fluorodeoxyglucose	O
+(	O
+F	O
+-	O
+18	O
+FDG	O
+)	O
+by	O
+a	O
+malignant	O
+tumor	O
+depends	O
+on	O
+the	O
+blood	O
+glucose	O
+level	O
+.	O
+
+This	O
+analysis	O
+supports	O
+the	O
+use	O
+of	O
+fluticasone	O
+propionate	O
+88	O
+microg	O
+twice	O
+daily	O
+as	O
+first	O
+-	O
+line	O
+treatment	O
+in	O
+patients	O
+with	O
+persistent	O
+asthma	O
+previously	O
+treated	O
+with	O
+short	O
+-	O
+acting	O
+beta2	B-GENE
+-	O
+agonist	O
+alone	O
+.	O
+
+By	O
+using	O
+space	O
+-	O
+discrete	O
+/	O
+continuous	O
+metapopulation	O
+dynamic	O
+models	O
+and	O
+computer	O
+simulations	O
+,	O
+we	O
+show	O
+that	O
+there	O
+can	O
+be	O
+two	O
+principally	O
+different	O
+regimes	O
+of	O
+metapopulation	O
+dynamics	O
+.	O
+
+Eight	O
+CAD	O
+patients	O
+who	O
+were	O
+matched	O
+to	O
+the	O
+treated	O
+patients	O
+for	O
+age	O
+(	O
++	O
+/	O
+-	O
+3	O
+years	O
+)	O
+,	O
+baseline	O
+low	B-GENE
+density	I-GENE
+lipoprotein	I-GENE
+(	O
++	O
+/	O
+-	O
+5	O
+mg	O
+/	O
+dL	O
+)	O
+,	O
+and	O
+triglycerides	O
+(	O
++	O
+/	O
+-	O
+50	O
+mg	O
+/	O
+dL	O
+)	O
+but	O
+who	O
+had	O
+never	O
+been	O
+treated	O
+with	O
+lipid	O
+-	O
+lowering	O
+drugs	O
+were	O
+selected	O
+as	O
+controls	O
+.	O
+
+RESULTS	O
+:	O
+A	O
+novel	O
+gene	O
+was	O
+cloned	O
+.	O
+
+The	O
+moduli	O
+of	O
+elasticity	O
+of	O
+the	O
+gray	O
+and	O
+white	O
+matter	O
+were	O
+3	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+kPa	O
+(	O
+mean	O
++	O
+/	O
+-	O
+standard	O
+deviation	O
+)	O
+and	O
+3	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+kPa	O
+in	O
+the	O
+axial	O
+section	O
+,	O
+3	O
++	O
+/	O
+-	O
+0	O
+.	O
+3	O
+kPa	O
+and	O
+3	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+kPa	O
+in	O
+the	O
+frontal	O
+section	O
+,	O
+and	O
+3	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+kPa	O
+and	O
+2	O
+.	O
+8	O
++	O
+/	O
+-	O
+0	O
+.	O
+4	O
+kPa	O
+in	O
+the	O
+sagittal	O
+section	O
+,	O
+respectively	O
+.	O
+
+Direct	O
+current	O
+polarography	O
+and	O
+differential	O
+pulse	O
+polarographic	O
+methods	O
+have	O
+been	O
+developed	O
+for	O
+the	O
+qualitative	O
+as	O
+well	O
+as	O
+quantitative	O
+analysis	O
+of	O
+vitamin	O
+B1	O
+,	O
+B2	O
+and	O
+B6	O
+.	O
+
+Against	O
+gram	O
+-	O
+positive	O
+organisms	O
+,	O
+E	O
+-	O
+4767	O
+and	O
+E	O
+-	O
+5065	O
+were	O
+,	O
+in	O
+general	O
+,	O
+eight	O
+-	O
+and	O
+fourfold	O
+more	O
+active	O
+than	O
+tosufloxacin	O
+,	O
+which	O
+is	O
+the	O
+most	O
+potent	O
+of	O
+the	O
+reference	O
+compounds	O
+.	O
+
+However	O
+,	O
+most	O
+produced	O
+significant	O
+alteration	O
+of	O
+small	O
+intestinal	O
+permeability	O
+.	O
+
+These	O
+included	O
+HNF	B-GENE
+-	I-GENE
+3	I-GENE
+beta	I-GENE
+,	O
+HFH	B-GENE
+-	I-GENE
+1	I-GENE
+,	O
+HFH	B-GENE
+-	I-GENE
+2	I-GENE
+,	O
+HFH	B-GENE
+-	I-GENE
+3	I-GENE
+,	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+,	O
+and	O
+C	B-GENE
+/	I-GENE
+EBP	I-GENE
+beta	I-GENE
+,	O
+all	O
+of	O
+which	O
+are	O
+consistent	O
+with	O
+the	O
+tissue	O
+-	O
+specific	O
+expression	O
+profiles	O
+of	O
+the	O
+gene	O
+.	O
+
+Managing	O
+vertigo	O
+and	O
+vertigo	O
+syndromes	O
+in	O
+the	O
+elderly	O
+
+The	O
+MABP	O
+and	O
+MCBFV	O
+signals	O
+were	O
+bandpass	O
+filtered	O
+in	O
+the	O
+very	O
+low	O
+-	O
+frequency	O
+range	O
+(	O
+VLF	O
+,	O
+0	O
+.	O
+015	O
+-	O
+0	O
+.	O
+07	O
+Hz	O
+)	O
+,	O
+low	O
+-	O
+frequency	O
+range	O
+(	O
+LF	O
+,	O
+0	O
+.	O
+07	O
+-	O
+0	O
+.	O
+15	O
+Hz	O
+)	O
+and	O
+high	O
+-	O
+frequency	O
+range	O
+(	O
+HF	O
+,	O
+0	O
+.	O
+15	O
+-	O
+0	O
+.	O
+40	O
+Hz	O
+)	O
+before	O
+applying	O
+CCF	O
+for	O
+the	O
+purpose	O
+of	O
+studying	O
+the	O
+effect	O
+of	O
+different	O
+bandwidths	O
+on	O
+the	O
+resulting	O
+mean	O
+CCFs	O
+.	O
+
+Hepatitis	O
+B	O
+and	O
+C	O
+seroprevalence	O
+rates	O
+among	O
+high	O
+-	O
+risk	O
+adolescents	O
+are	O
+lower	O
+in	O
+El	O
+Paso	O
+than	O
+in	O
+other	O
+similar	O
+US	O
+populations	O
+,	O
+presenting	O
+an	O
+ideal	O
+climate	O
+for	O
+prevention	O
+programs	O
+.	O
+
+A	O
+twelfth	O
+insertion	O
+disrupts	O
+two	O
+genes	O
+,	O
+Nrk	B-GENE
+,	O
+a	O
+"	B-GENE
+neurospecific	I-GENE
+"	I-GENE
+receptor	I-GENE
+tyrosine	I-GENE
+kinase	I-GENE
+,	O
+and	O
+Tpp	B-GENE
+,	O
+which	O
+encodes	O
+a	O
+neuropeptidase	B-GENE
+.	O
+
+Not	O
+Available	O
+
+This	O
+unique	O
+work	O
+needs	O
+to	O
+be	O
+edited	O
+critically	O
+and	O
+afterwards	O
+translated	O
+into	O
+Urdu	O
+and	O
+other	O
+languages	O
+for	O
+the	O
+benefit	O
+of	O
+the	O
+present	O
+day	O
+students	O
+and	O
+scholars	O
+.	O
+
+Comparison	O
+of	O
+German	O
+language	O
+versions	O
+of	O
+the	O
+QWB	O
+-	O
+SA	O
+and	O
+SF	O
+-	O
+36	O
+evaluating	O
+outcomes	O
+for	O
+patients	O
+with	O
+prostate	O
+disease	O
+.	O
+
+Disciplinary	O
+action	O
+for	O
+DNA	O
+violation	O
+.	O
+
+Epithelial	O
+cytotoxicity	O
+of	O
+combined	O
+antibiotics	O
+was	O
+additive	O
+,	O
+with	O
+no	O
+evidence	O
+of	O
+competition	O
+or	O
+synergism	O
+.	O
+
+Pro	O
+-	O
+inflammatory	O
+cytokine	O
+,	O
+tumor	B-GENE
+necrosis	I-GENE
+factor	I-GENE
+-	I-GENE
+alpha	I-GENE
+(	O
+TNF	B-GENE
+-	I-GENE
+alpha	I-GENE
+)	O
+,	O
+produced	O
+from	O
+adipose	O
+tissues	O
+in	O
+obese	O
+subjects	O
+,	O
+is	O
+known	O
+to	O
+play	O
+a	O
+predominant	O
+role	O
+in	O
+inducing	O
+insulin	B-GENE
+resistance	O
+.	O
+
+The	O
+most	O
+important	O
+finding	O
+,	O
+however	O
+,	O
+was	O
+that	O
+IMT	O
+values	O
+were	O
+related	O
+with	O
+24	O
+h	O
+SBP	O
+or	O
+PP	O
+standard	O
+deviation	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+a	O
+measure	O
+of	O
+overall	O
+SBP	O
+or	O
+PP	O
+variability	O
+.	O
+
+The	O
+difference	O
+between	O
+the	O
+patients	O
+and	O
+the	O
+controls	O
+was	O
+statistically	O
+significant	O
+(	O
+p	O
+=	O
+0	O
+.	O
+03	O
+)	O
+.	O
+
+The	O
+effect	O
+of	O
+crude	O
+oil	O
+spillage	O
+on	O
+growth	O
+,	O
+productivity	O
+and	O
+nutrient	O
+uptake	O
+of	O
+maize	O
+(	O
+Zea	O
+mays	O
+L	O
+.	O
+)	O
+was	O
+assessed	O
+in	O
+a	O
+pot	O
+experiment	O
+using	O
+an	O
+Evwreni	O
+manifold	O
+sample	O
+of	O
+a	O
+petroleum	O
+development	O
+company	O
+,	O
+which	O
+had	O
+a	O
+specific	O
+gravity	O
+of	O
+0	O
+.	O
+8778	O
+.	O
+
+NO	O
+metabolites	O
+were	O
+determined	O
+by	O
+the	O
+measurement	O
+of	O
+nitrate	O
+/	O
+nitrite	O
+(	O
+NOx	O
+,	O
+micromol	O
+/	O
+mmol	O
+creatinine	O
+)	O
+and	O
+cyclic	O
+guanosine	O
+monophosphate	O
+(	O
+cGMP	O
+,	O
+nmol	O
+/	O
+mmol	O
+creatinine	O
+)	O
+in	O
+plasma	O
+and	O
+urine	O
+.	O
+
+In	O
+the	O
+base	O
+-	O
+case	O
+analysis	O
+,	O
+total	O
+direct	O
+costs	O
+per	O
+patient	O
+were	O
+$	O
+728	O
+for	O
+zoledronic	O
+acid	O
+and	O
+$	O
+776	O
+for	O
+pamidronate	O
+.	O
+
+The	O
+diet	O
+of	O
+migrants	O
+showed	O
+both	O
+positive	O
+(	O
+macronutrients	O
+)	O
+and	O
+negative	O
+(	O
+micronutrients	O
+)	O
+differences	O
+with	O
+the	O
+general	O
+Dutch	O
+diet	O
+.	O
+
+C	O
+.	O
+elegans	O
+embryogenesis	O
+begins	O
+with	O
+a	O
+stereotyped	O
+sequence	O
+of	O
+asymmetric	O
+cell	O
+divisions	O
+that	O
+are	O
+largely	O
+responsible	O
+for	O
+establishing	O
+the	O
+nematode	O
+body	O
+plan	O
+.	O
+
+Finally	O
+,	O
+a	O
+chromogenic	O
+method	O
+was	O
+used	O
+,	O
+based	O
+on	O
+thrombin	B-GENE
+inhibition	O
+and	O
+the	O
+substrate	O
+S	O
+-	O
+2238	O
+.	O
+
+[	O
+Diabetologia	O
+(	O
+2001	O
+)	O
+44	O
+[	O
+Suppl	O
+3	O
+]	O
+:	O
+B37	O
+-	O
+B44	O
+]	O
+
+The	O
+5	O
+'	O
+flanking	O
+sequence	O
+of	O
+the	O
+3B	B-GENE
+gene	I-GENE
+is	O
+extremely	O
+A	O
++	O
+T	O
+rich	O
+but	O
+contains	O
+five	O
+G	O
+/	O
+C	O
+rich	O
+stretches	O
+,	O
+each	O
+approximately	O
+7bp	O
+long	O
+,	O
+which	O
+have	O
+strong	O
+sequence	O
+similarity	O
+to	O
+the	O
+G	O
+boxes	O
+found	O
+upstream	O
+of	O
+other	O
+developmentally	O
+regulated	O
+Dictyostelium	O
+genes	O
+.	O
+
+Considering	O
+that	O
+the	O
+reactor	O
+is	O
+thoroughly	O
+mixed	O
+during	O
+each	O
+discharge	O
+and	O
+that	O
+LD50	O
+=	O
+0	O
+.	O
+9	O
+values	O
+are	O
+nearly	O
+independent	O
+of	O
+E	O
+.	O
+coli	O
+concentrations	O
+in	O
+the	O
+range	O
+of	O
+2	O
+x	O
+10	O
+(	O
+3	O
+)	O
+<	O
+or	O
+=	O
+E	O
+coli	O
+/	O
+cfu	O
+mL	O
+(	O
+-	O
+1	O
+)	O
+<	O
+or	O
+=	O
+3	O
+x	O
+10	O
+(	O
+6	O
+)	O
+,	O
+we	O
+ascribe	O
+the	O
+nonexponential	O
+Pn	O
+decay	O
+of	O
+single	O
+-	O
+strain	O
+E	O
+.	O
+coli	O
+colonies	O
+to	O
+a	O
+shielding	O
+phenomenon	O
+where	O
+inactive	O
+cells	O
+protect	O
+the	O
+successively	O
+smaller	O
+numbers	O
+of	O
+viable	O
+cells	O
+in	O
+the	O
+EHD	O
+.	O
+
+In	O
+the	O
+long	O
+term	O
+,	O
+questions	O
+still	O
+remain	O
+about	O
+whether	O
+pre	O
+-	O
+dialysis	O
+rHu	B-GENE
+EPO	I-GENE
+either	O
+speeds	O
+up	O
+or	O
+delays	O
+the	O
+onset	O
+of	O
+dialysis	O
+.	O
+
+METHODS	O
+:	O
+This	O
+retrospective	O
+review	O
+comprised	O
+2711	O
+eyes	O
+that	O
+had	O
+LASIK	O
+between	O
+September	O
+1996	O
+and	O
+September	O
+1999	O
+.	O
+
+No	O
+ISREs	B-GENE
+could	O
+be	O
+identified	O
+in	O
+the	O
+mouse	O
+promoter	O
+.	O
+
+BACKGROUND	O
+:	O
+Ischemic	O
+heart	O
+disease	O
+is	O
+the	O
+primary	O
+cause	O
+of	O
+morbidity	O
+and	O
+mortality	O
+among	O
+diabetics	O
+,	O
+especially	O
+those	O
+who	O
+became	O
+ill	O
+at	O
+a	O
+young	O
+age	O
+.	O
+
+A	O
+38	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+ulcerative	O
+colitis	O
+subsequently	O
+developed	O
+sarcoidosis	O
+.	O
+
+Cholesteryl	B-GENE
+ester	I-GENE
+transfer	I-GENE
+protein	I-GENE
+and	O
+atherosclerosis	O
+in	O
+Japanese	O
+subjects	O
+:	O
+a	O
+study	O
+based	O
+on	O
+coronary	O
+angiography	O
+.	O
+
+Electrophoretic	O
+mobility	O
+shift	O
+assays	O
+and	O
+coimmunoprecipitation	O
+studies	O
+suggest	O
+that	O
+homo	O
+-	O
+and	O
+heterodimerization	O
+occurs	O
+between	O
+cKrox	B-GENE
+family	I-GENE
+members	I-GENE
+.	O
+
+The	O
+hcKrox	B-GENE
+gene	O
+family	O
+regulates	O
+multiple	O
+extracellular	O
+matrix	O
+genes	O
+.	O
+
+A	O
+review	O
+of	O
+the	O
+literature	O
+identified	O
+8	O
+comprehensive	O
+clinical	O
+studies	O
+,	O
+all	O
+of	O
+which	O
+failed	O
+to	O
+document	O
+any	O
+relationship	O
+between	O
+NF1	B-GENE
+and	O
+intracranial	O
+aneurysms	O
+.	O
+
+These	O
+utilisation	O
+data	O
+imply	O
+annual	O
+drug	O
+costs	O
+in	O
+the	O
+range	O
+of	O
+$	O
+US	O
+480	O
+,	O
+000	O
+to	O
+$	O
+US	O
+3	O
+,	O
+600	O
+,	O
+000	O
+for	O
+TNF	B-GENE
+antagonists	O
+for	O
+RA	O
+per	O
+1	O
+million	O
+population	O
+.	O
+
+This	O
+study	O
+investigated	O
+whether	O
+boron	O
+would	O
+enhance	O
+the	O
+ability	O
+of	O
+17beta	O
+-	O
+estradiol	O
+(	O
+E2	O
+)	O
+or	O
+parathyroid	B-GENE
+hormone	I-GENE
+(	O
+PTH	B-GENE
+)	O
+to	O
+improve	O
+bone	O
+quality	O
+in	O
+ovariectomized	O
+OVX	O
+rats	O
+.	O
+
+We	O
+found	O
+in	O
+the	O
+control	O
+subjects	O
+rCBF	O
+increases	O
+in	O
+regions	O
+associated	O
+with	O
+the	O
+meso	O
+-	O
+striatal	O
+and	O
+meso	O
+-	O
+corticolimbic	O
+circuits	O
+in	O
+response	O
+to	O
+both	O
+monetary	O
+reward	O
+and	O
+nonmonetary	O
+reinforcement	O
+.	O
+
+Doxorubicin	O
+(	O
+DOX	O
+)	O
+is	O
+commonly	O
+used	O
+for	O
+the	O
+treatment	O
+of	O
+hematological	O
+and	O
+solid	O
+tumors	O
+.	O
+
+The	O
+event	O
+rate	O
+in	O
+patients	O
+with	O
+chronic	O
+Irr	O
+-	O
+rMFP	O
+or	O
+Un	O
+-	O
+nrMFP	O
+was	O
+markedly	O
+higher	O
+than	O
+it	O
+was	O
+in	O
+those	O
+with	O
+Rev	O
+-	O
+rMFP	O
+or	O
+Sta	O
+-	O
+nrMFP	O
+.	O
+
+Subtraction	O
+hybridization	O
+identified	O
+melanoma	B-GENE
+differentiation	I-GENE
+associated	I-GENE
+gene	I-GENE
+-	I-GENE
+7	I-GENE
+(	O
+mda	B-GENE
+-	I-GENE
+7	I-GENE
+)	O
+,	O
+as	O
+a	O
+gene	O
+induced	O
+during	O
+these	O
+physiological	O
+changes	O
+in	O
+human	O
+melanoma	O
+cells	O
+.	O
+
+Therefore	O
+,	O
+vitamin	O
+D3	O
+analogues	O
+have	O
+a	O
+substantial	O
+antipsoriatic	O
+effect	O
+.	O
+
+Hydrocoele	O
+is	O
+common	O
+in	O
+men	O
+in	O
+Wuchereria	O
+bancrofti	O
+-	O
+endemic	O
+areas	O
+,	O
+the	O
+treatment	O
+for	O
+which	O
+is	O
+currently	O
+surgical	O
+intervention	O
+.	O
+
+Growth	B-GENE
+hormone	I-GENE
+and	O
+insulin	B-GENE
+-	I-GENE
+like	I-GENE
+growth	I-GENE
+factor	I-GENE
+I	I-GENE
+receptors	I-GENE
+in	O
+the	O
+temporomandibular	O
+joint	O
+of	O
+the	O
+rat	O
+.	O
+
+In	O
+addition	O
+to	O
+that	O
+,	O
+she	O
+received	O
+hepatic	O
+intra	O
+-	O
+arterial	O
+infusion	O
+of	O
+levoforinate	O
+(	O
+l	O
+-	O
+LV	O
+)	O
+250	O
+mg	O
+and	O
+5	O
+-	O
+fluorouracil	O
+(	O
+5	O
+-	O
+FU	O
+)	O
+500	O
+mg	O
+for	O
+combined	O
+multiple	O
+hepatic	O
+metastases	O
+starting	O
+on	O
+postoperative	O
+day	O
+14	O
+,	O
+and	O
+these	O
+medications	O
+were	O
+administered	O
+over	O
+48	O
+hours	O
+once	O
+weekly	O
+by	O
+infuser	O
+pump	O
+.	O
+
+The	O
+astronaut	O
+crew	O
+operates	O
+the	O
+payload	O
+and	O
+documents	O
+its	O
+operation	O
+.	O
+
+For	O
+these	O
+patients	O
+the	O
+introduction	O
+of	O
+a	O
+separate	O
+category	O
+"	O
+extended	O
+oligoarthritis	O
+at	O
+onset	O
+"	O
+should	O
+be	O
+considered	O
+to	O
+establish	O
+comparable	O
+patient	O
+groups	O
+.	O
+
+Phase	O
+II	O
+trial	O
+of	O
+the	O
+anti	B-GENE
+-	I-GENE
+G	I-GENE
+(	I-GENE
+D2	I-GENE
+)	I-GENE
+monoclonal	I-GENE
+antibody	I-GENE
+3F8	I-GENE
+and	O
+granulocyte	B-GENE
+-	I-GENE
+macrophage	I-GENE
+colony	I-GENE
+-	I-GENE
+stimulating	I-GENE
+factor	I-GENE
+for	O
+neuroblastoma	O
+.	O
+
+Hepatitis	O
+A	O
+infected	O
+food	O
+handler	O
+at	O
+an	O
+Edmonton	O
+,	O
+Alberta	O
+retail	O
+food	O
+facility	O
+:	O
+public	O
+health	O
+protection	O
+strategies	O
+.	O
+
+Hydrogels	O
+for	O
+tissue	O
+engineering	O
+.	O
+
+Eliminating	O
+any	O
+subset	O
+of	O
+ASCUS	O
+reduces	O
+the	O
+ASCUS	O
+/	O
+SIL	O
+ratio	O
+but	O
+also	O
+significantly	O
+diminishes	O
+the	O
+sensitivity	O
+of	O
+the	O
+Papanicolaou	O
+test	O
+.	O
+
+Eliminating	O
+any	O
+subset	O
+of	O
+ASCUS	O
+reduces	O
+the	O
+ASCUS	O
+/	O
+SIL	O
+ratio	O
+but	O
+also	O
+significantly	O
+diminishes	O
+the	O
+sensitivity	O
+of	O
+the	O
+Papanicolaou	O
+test	O
+.	O
+
+Two	O
+nuclear	O
+medicine	O
+physicians	O
+blinded	O
+to	O
+the	O
+surgical	O
+findings	O
+interpreted	O
+all	O
+available	O
+images	O
+and	O
+various	O
+Tc	O
+-	O
+99m	O
+MIBI	O
+image	O
+combinations	O
+at	O
+15	O
+minutes	O
+alone	O
+;	O
+15	O
+minutes	O
+and	O
+2	O
+hours	O
+,	O
+15	O
+minutes	O
+and	O
+4	O
+hours	O
+;	O
+and	O
+15	O
+minutes	O
+and	O
+2	O
+and	O
+4	O
+hours	O
+each	O
+with	O
+and	O
+without	O
+correlative	O
+pertechnetate	O
+thyroid	O
+imaging	O
+.	O
+
+Between	O
+1967	O
+and	O
+1994	O
+,	O
+495	O
+patients	O
+underwent	O
+surgery	O
+for	O
+primary	O
+PTC	O
+at	O
+the	O
+Department	O
+of	O
+Surgery	O
+,	O
+Helsinki	O
+University	O
+Central	O
+Hospital	O
+.	O
+
+ISS	O
+and	O
+the	O
+acute	O
+physiology	O
+and	O
+chronic	O
+health	O
+evaluation	O
+(	O
+APACHE	O
+II	O
+)	O
+calculated	O
+on	O
+admission	O
+.	O
+
+The	O
+procedure	O
+is	O
+less	O
+aggressive	O
+and	O
+painful	O
+than	O
+sternotomy	O
+.	O
+
+Paul	O
+Monagle	O
+addresses	O
+the	O
+epidemiology	O
+of	O
+neonatal	O
+thrombosis	O
+outside	O
+of	O
+the	O
+central	O
+nervous	O
+system	O
+in	O
+both	O
+arterial	O
+and	O
+venous	O
+locations	O
+,	O
+and	O
+those	O
+that	O
+occur	O
+in	O
+utero	O
+.	O
+
+[	O
+Clinical	O
+and	O
+epidemiological	O
+characteristics	O
+of	O
+squamous	O
+cell	O
+carcinoma	O
+of	O
+the	O
+oral	O
+cavity	O
+in	O
+women	O
+]	O
+BACKGROUND	O
+:	O
+Squamous	O
+cell	O
+carcinoma	O
+(	O
+SCC	O
+)	O
+of	O
+the	O
+oral	O
+cavity	O
+occurs	O
+mainly	O
+in	O
+the	O
+male	O
+population	O
+.	O
+
+Regarding	O
+gestational	O
+risk	O
+,	O
+3	O
+,	O
+243	O
+drugs	O
+used	O
+(	O
+34	O
+%	O
+)	O
+belonged	O
+to	O
+category	O
+A	O
+risk	O
+,	O
+1	O
+,	O
+923	O
+(	O
+22	O
+.	O
+6	O
+%	O
+)	O
+to	O
+category	O
+B	O
+,	O
+3	O
+,	O
+798	O
+(	O
+39	O
+.	O
+7	O
+%	O
+)	O
+to	O
+category	O
+C	O
+,	O
+289	O
+(	O
+3	O
+.	O
+0	O
+%	O
+)	O
+to	O
+category	O
+D	O
+,	O
+and	O
+55	O
+(	O
+0	O
+.	O
+6	O
+%	O
+)	O
+to	O
+category	O
+X	O
+.	O
+
+The	O
+process	O
+has	O
+been	O
+applied	O
+to	O
+the	O
+river	O
+reclamation	O
+in	O
+Yangpu	O
+District	O
+of	O
+Shanghai	O
+City	O
+,	O
+China	O
+.	O
+
+Physical	O
+principles	O
+in	O
+therapeutic	O
+apheresis	O
+.	O
+
+Rind	O
+et	O
+al	O
+.	O
+'	O
+s	O
+study	O
+'	O
+s	O
+main	O
+conclusions	O
+were	O
+not	O
+supported	O
+by	O
+the	O
+original	O
+data	O
+.	O
+
+Of	O
+major	O
+concern	O
+to	O
+food	O
+processors	O
+is	O
+the	O
+inadvertent	O
+cross	O
+-	O
+contact	O
+of	O
+food	O
+products	O
+with	O
+allergenic	O
+residues	O
+,	O
+which	O
+could	O
+result	O
+in	O
+potentially	O
+life	O
+-	O
+threatening	O
+reactions	O
+in	O
+those	O
+with	O
+a	O
+food	O
+allergy	O
+.	O
+
+Lactate	O
+accumulation	O
+peak	O
+was	O
+unaffected	O
+by	O
+supplementation	O
+(	O
+HMB	O
+,	O
+8	O
+.	O
+1	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+mM	O
+;	O
+LEU	O
+,	O
+6	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+mM	O
+;	O
+CON	O
+,	O
+7	O
+.	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+mM	O
+)	O
+.	O
+
+The	O
+increased	O
+clearance	O
+observed	O
+in	O
+young	O
+infants	O
+is	O
+in	O
+contrast	O
+to	O
+other	O
+opioids	O
+.	O
+
+These	O
+results	O
+were	O
+robust	O
+to	O
+changes	O
+in	O
+the	O
+baseline	O
+assumptions	O
+of	O
+the	O
+model	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+training	O
+of	O
+novices	O
+using	O
+MIST	O
+-	O
+VR	O
+yields	O
+quantifiable	O
+changes	O
+in	O
+skill	O
+that	O
+are	O
+transferable	O
+to	O
+a	O
+simple	O
+real	O
+task	O
+and	O
+are	O
+similar	O
+to	O
+the	O
+results	O
+achieved	O
+with	O
+conventional	O
+training	O
+.	O
+
+The	O
+patients	O
+and	O
+their	O
+families	O
+were	O
+closely	O
+questioned	O
+,	O
+and	O
+full	O
+clinical	O
+examination	O
+included	O
+a	O
+test	O
+for	O
+orthostasia	O
+.	O
+
+They	O
+have	O
+not	O
+been	O
+previously	O
+reported	O
+as	O
+a	O
+reaction	O
+to	O
+i	O
+.	O
+v	O
+.	O
+contrast	O
+material	O
+.	O
+
+There	O
+was	O
+a	O
+statistically	O
+significant	O
+correlation	O
+between	O
+simultaneous	O
+weekly	O
+average	O
+pollen	O
+levels	O
+in	O
+Philadelphia	O
+and	O
+in	O
+Cherry	O
+Hill	O
+(	O
+Acer	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+987	O
+,	O
+Quercus	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+645	O
+,	O
+Betula	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+896	O
+,	O
+Pinus	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+732	O
+,	O
+Cupressaceae	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+695	O
+,	O
+Poaceae	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+950	O
+,	O
+Ambrosia	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+903	O
+,	O
+and	O
+Rumex	O
+,	O
+r	O
+(	O
+p	O
+)	O
+=	O
+0	O
+.	O
+572	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Encouraged	O
+by	O
+a	O
+Dutch	O
+study	O
+using	O
+etidronate	O
+/	O
+fluoride	O
+in	O
+corticoid	O
+-	O
+induced	O
+osteoporosis	O
+,	O
+we	O
+performed	O
+a	O
+pilot	O
+study	O
+in	O
+33	O
+men	O
+with	O
+severe	O
+established	O
+primary	O
+osteoporosis	O
+giving	O
+cyclically	O
+etidronate	O
+for	O
+14	O
+days	O
+followed	O
+by	O
+fluoride	O
+plus	O
+calcium	O
+/	O
+vitamin	O
+D	O
+for	O
+76	O
+days	O
+.	O
+
+In	O
+order	O
+to	O
+overcome	O
+the	O
+false	O
+positive	O
+readings	O
+that	O
+are	O
+possible	O
+in	O
+sphincter	O
+manometry	O
+,	O
+we	O
+proposed	O
+to	O
+use	O
+secretin	B-GENE
+stimulated	O
+endoscopic	O
+ultrasound	O
+(	O
+SSEUS	O
+)	O
+to	O
+measure	O
+pancreatic	O
+ductal	O
+response	O
+as	O
+an	O
+adjunctive	O
+method	O
+to	O
+aid	O
+and	O
+supplement	O
+the	O
+diagnosis	O
+.	O
+
+The	O
+cut	O
+-	O
+off	O
+percentage	O
+positivity	O
+value	O
+was	O
+established	O
+using	O
+500	O
+brucellosis	O
+-	O
+positive	O
+and	O
+500	O
+brucellosis	O
+-	O
+negative	O
+serum	O
+samples	O
+,	O
+confirmed	O
+with	O
+reference	O
+to	O
+the	O
+sample	O
+data	O
+using	O
+the	O
+indirect	O
+ELISA	O
+kit	O
+.	O
+
+An	O
+analysis	O
+of	O
+the	O
+dynamics	O
+is	O
+performed	O
+of	O
+exactly	O
+solvable	O
+models	O
+for	O
+fragile	O
+and	O
+strong	O
+glasses	O
+,	O
+exploiting	O
+the	O
+partitioning	O
+of	O
+the	O
+free	O
+-	O
+energy	O
+landscape	O
+in	O
+inherent	O
+structures	O
+.	O
+
+Fifty	O
+-	O
+six	O
+semen	O
+samples	O
+were	O
+included	O
+in	O
+this	O
+study	O
+;	O
+18	O
+were	O
+subnormal	O
+(	O
+G1	O
+)	O
+and	O
+38	O
+were	O
+normal	O
+(	O
+G2	O
+)	O
+based	O
+on	O
+World	O
+Health	O
+Organization	O
+criteria	O
+,	O
+except	O
+for	O
+morphology	O
+,	O
+which	O
+was	O
+evaluated	O
+according	O
+to	O
+strict	O
+criteria	O
+.	O
+
+At	O
+this	O
+timepoint	O
+,	O
+many	O
+leucocytes	O
+in	O
+the	O
+ME	O
+and	O
+ET	O
+mucosa	O
+had	O
+incorporated	O
+BrdU	O
+(	O
+between	O
+15	O
+and	O
+25	O
+%	O
+within	O
+the	O
+subsets	O
+)	O
+.	O
+
+Their	O
+chemical	O
+structures	O
+were	O
+elucidated	O
+as	O
+1	O
+alpha	O
+,	O
+2	O
+alpha	O
+-	O
+diacetoxy	O
+-	O
+8	O
+beta	O
+-	O
+isobutanoyloxy	O
+-	O
+9	O
+alpha	O
+-	O
+benzoyloxy	O
+-	O
+13	O
+-	O
+(	O
+alpha	O
+-	O
+methyl	O
+)	O
+butanoyloxy	O
+-	O
+4	O
+beta	O
+,	O
+6	O
+beta	O
+-	O
+dihydroxy	O
+-	O
+beta	O
+-	O
+dihydroagarofuran	O
+(	O
+1	O
+)	O
+,	O
+1	O
+alpha	O
+,	O
+2	O
+alpha	O
+-	O
+diacetoxy	O
+-	O
+8	O
+beta	O
+-	O
+(	O
+beta	O
+-	O
+furancarbonyloxy	O
+)	O
+-	O
+9	O
+alpha	O
+-	O
+benzoyloxy	O
+-	O
+13	O
+-	O
+isobutanoyloxy	O
+-	O
+4	O
+beta	O
+,	O
+6	O
+beta	O
+-	O
+dihydroxy	O
+-	O
+beta	O
+-	O
+dihydroagarofuran	O
+(	O
+2	O
+)	O
+and	O
+1	O
+alpha	O
+,	O
+6	O
+beta	O
+,	O
+8	O
+alpha	O
+,	O
+13	O
+-	O
+tetraacetoxy	O
+-	O
+9	O
+alpha	O
+-	O
+benzoyloxy	O
+-	O
+2	O
+alpha	O
+-	O
+hydroxy	O
+-	O
+beta	O
+-	O
+dihydroagarofuran	O
+(	O
+3	O
+)	O
+mainly	O
+by	O
+analyses	O
+NMR	O
+and	O
+MS	O
+spectral	O
+data	O
+.	O
+
+Saunders	O
+Company	O
+.	O
+
+Acute	O
+stress	O
+in	O
+7	O
+rats	O
+also	O
+increased	O
+the	O
+mean	O
+amount	O
+of	O
+IL	B-GENE
+-	I-GENE
+6	I-GENE
+released	O
+in	O
+the	O
+urine	O
+by	O
+31	O
+.	O
+5	O
+%	O
+from	O
+775	O
+.	O
+9	O
++	O
+/	O
+-	O
+69	O
+.	O
+2	O
+to	O
+1	O
+,	O
+021	O
+.	O
+1	O
++	O
+/	O
+-	O
+93	O
+.	O
+3	O
+pg	O
+.	O
+/	O
+ml	O
+.	O
+
+Patients	O
+with	O
+CF	O
+and	O
+meconium	O
+ileus	O
+presented	O
+a	O
+poor	O
+nutritional	O
+status	O
+at	O
+diagnosis	O
+and	O
+a	O
+lower	O
+survival	O
+rate	O
+compared	O
+to	O
+the	O
+general	O
+CF	O
+population	O
+.	O
+
+(	O
+Cactaceae	O
+)	O
+waste	O
+matter	O
+.	O
+
+Skin	O
+cancers	O
+,	O
+followed	O
+by	O
+gastrointestinal	O
+tract	O
+and	O
+male	O
+genital	O
+system	O
+affected	O
+mostly	O
+older	O
+age	O
+patients	O
+.	O
+
+CONCLUSION	O
+:	O
+MMF	O
+(	O
+2	O
+-	O
+3	O
+g	O
+/	O
+day	O
+)	O
+is	O
+unable	O
+to	O
+control	O
+the	O
+signs	O
+of	O
+mucocutaneous	O
+Adamantiades	O
+-	O
+Behcet	O
+'	O
+s	O
+disease	O
+.	O
+
+In	O
+the	O
+treatment	O
+of	O
+opioid	O
+naive	O
+patients	O
+who	O
+underwent	O
+surgery	O
+and	O
+received	O
+opioids	O
+for	O
+acute	O
+pain	O
+,	O
+oral	O
+ADL	O
+8	O
+-	O
+2698	O
+(	O
+6	O
+.	O
+0	O
+mg	O
+)	O
+improved	O
+the	O
+management	O
+of	O
+postoperative	O
+ileus	O
+(	O
+POI	O
+)	O
+by	O
+shortening	O
+the	O
+time	O
+to	O
+achieve	O
+normal	O
+bowel	O
+function	O
+and	O
+,	O
+ultimately	O
+,	O
+hospital	O
+stay	O
+.	O
+
+Evidence	O
+suggests	O
+that	O
+PHACES	O
+syndrome	O
+is	O
+not	O
+a	O
+random	O
+association	O
+but	O
+a	O
+true	O
+phakomatosis	O
+;	O
+further	O
+studies	O
+are	O
+awaited	O
+to	O
+shed	O
+light	O
+on	O
+a	O
+possible	O
+genetic	O
+background	O
+.	O
+
+Moreover	O
+,	O
+a	O
+severe	O
+decrease	O
+of	O
+antithrombin	B-GENE
+activity	O
+became	O
+evident	O
+during	O
+both	O
+experiments	O
+(	O
+eg	O
+,	O
+in	O
+experiment	O
+2	O
+from	O
+95	O
+.	O
+6	O
++	O
+/	O
+-	O
+4	O
+.	O
+8	O
+to	O
+59	O
+.	O
+2	O
++	O
+/	O
+-	O
+6	O
+.	O
+6	O
+%	O
+)	O
+.	O
+
+The	O
+Penn	O
+State	O
+Worry	O
+Questionnaire	O
+for	O
+Children	O
+(	O
+PSWQ	O
+-	O
+C	O
+)	O
+is	O
+a	O
+14	O
+-	O
+item	O
+self	O
+-	O
+report	O
+questionnaire	O
+that	O
+intends	O
+to	O
+measure	O
+the	O
+tendency	O
+of	O
+children	O
+to	O
+engage	O
+in	O
+excessive	O
+,	O
+generalized	O
+,	O
+and	O
+uncontrollable	O
+worry	O
+(	O
+Chorpita	O
+et	O
+al	O
+.	O
+,	O
+Behav	O
+.	O
+
+Described	O
+X	O
+-	O
+ray	O
+projection	O
+were	O
+performed	O
+in	O
+70	O
+patients	O
+.	O
+
+Pyrethroid	O
+insecticides	O
+are	O
+widely	O
+used	O
+in	O
+agriculture	O
+and	O
+private	O
+households	O
+.	O
+
+The	O
+sorption	O
+mechanisms	O
+changed	O
+from	O
+adsorption	O
+to	O
+partition	O
+in	O
+the	O
+process	O
+of	O
+repetitious	O
+sorption	O
+.	O
+
+Although	O
+the	O
+spatial	O
+and	O
+temporal	O
+variability	O
+of	O
+LDF	O
+signals	O
+evoked	O
+by	O
+cerebrocortical	O
+microflow	O
+is	O
+in	O
+the	O
+same	O
+range	O
+as	O
+with	O
+other	O
+methods	O
+and	O
+in	O
+other	O
+organs	O
+,	O
+LDF	O
+cerebrocortical	O
+mapping	O
+is	O
+restricted	O
+by	O
+the	O
+large	O
+temporal	O
+and	O
+spatial	O
+heterogeneity	O
+of	O
+the	O
+cerebrocortical	O
+vasculature	O
+.	O
+
+The	O
+5	O
+-	O
+year	O
+overall	O
+survival	O
+(	O
+OS	O
+)	O
+and	O
+progression	O
+-	O
+free	O
+survival	O
+(	O
+PFS	O
+)	O
+rates	O
+were	O
+58	O
+.	O
+9	O
+%	O
+and	O
+55	O
+.	O
+4	O
+%	O
+for	O
+arm	O
+A	O
+and	O
+44	O
+.	O
+5	O
+%	O
+and	O
+41	O
+.	O
+3	O
+%	O
+for	O
+arm	O
+B	O
+(	O
+P	O
+=	O
+.	O
+007	O
+and	O
+P	O
+=	O
+.	O
+02	O
+)	O
+,	O
+respectively	O
+.	O
+
+METHODS	O
+:	O
+P	B-GENE
+-	I-GENE
+selectin	I-GENE
+expression	O
+of	O
+nonstimulated	O
+and	O
+ADP	O
+-	O
+stimulated	O
+platelets	O
+was	O
+flow	O
+cytometrically	O
+measured	O
+before	O
+the	O
+clopidogrel	O
+loading	O
+dose	O
+and	O
+on	O
+3	O
+consecutive	O
+days	O
+in	O
+52	O
+patients	O
+with	O
+coronary	O
+artery	O
+disease	O
+:	O
+21	O
+patients	O
+in	O
+group	O
+1	O
+received	O
+300	O
+mg	O
+of	O
+clopidogrel	O
+after	O
+stent	O
+implantation	O
+and	O
+11	O
+patients	O
+in	O
+group	O
+2	O
+received	O
+the	O
+higher	O
+450	O
+-	O
+mg	O
+clopidogrel	O
+loading	O
+dose	O
+followed	O
+by	O
+a	O
+daily	O
+dose	O
+of	O
+75	O
+mg	O
+of	O
+clopidogrel	O
+for	O
+both	O
+groups	O
+.	O
+
+Traditional	O
+surgical	O
+exploration	O
+was	O
+followed	O
+by	O
+survey	O
+with	O
+a	O
+gamma	O
+-	O
+detecting	O
+probe	O
+.	O
+
+No	O
+effect	O
+of	O
+the	O
+intervention	O
+on	O
+depression	O
+scores	O
+was	O
+found	O
+.	O
+
+IV	O
+.	O
+combined	O
+sclerosis	O
+and	O
+resorption	O
+of	O
+the	O
+skull	O
+base	O
+(	O
+6	O
+cases	O
+,	O
+2	O
+group	O
+I	O
+lesions	O
+and	O
+4	O
+group	O
+II	O
+lesions	O
+)	O
+.	O
+
+The	O
+quantity	O
+of	O
+each	O
+population	O
+(	O
+L	O
+.	O
+bulgaricus	O
+,	O
+S	O
+.	O
+thermophilus	O
+)	O
+was	O
+then	O
+estimated	O
+in	O
+the	O
+pellet	O
+by	O
+PyMS	O
+,	O
+and	O
+the	O
+data	O
+were	O
+analysed	O
+by	O
+artificial	O
+neural	O
+networks	O
+(	O
+ANNs	O
+)	O
+.	O
+
+AF	B-GENE
+showed	O
+a	O
+mixed	O
+nuclear	O
+/	O
+cytoplasmic	O
+pattern	O
+of	O
+expression	O
+in	O
+the	O
+epithelial	O
+,	O
+endothelial	O
+,	O
+and	O
+stromal	O
+component	O
+of	O
+the	O
+normal	O
+breast	O
+and	O
+benign	O
+lesions	O
+,	O
+whereas	O
+an	O
+impressive	O
+loss	O
+of	O
+AF	B-GENE
+expression	O
+was	O
+noted	O
+in	O
+in	O
+situ	O
+and	O
+invasive	O
+breast	O
+cancer	O
+and	O
+tumoral	O
+stroma	O
+.	O
+
+We	O
+derive	O
+joint	O
+probability	O
+density	O
+distributions	O
+for	O
+three	O
+key	O
+uncertain	O
+properties	O
+of	O
+the	O
+climate	O
+system	O
+,	O
+using	O
+an	O
+optimal	O
+fingerprinting	O
+approach	O
+to	O
+compare	O
+simulations	O
+of	O
+an	O
+intermediate	O
+complexity	O
+climate	O
+model	O
+with	O
+three	O
+distinct	O
+diagnostics	O
+of	O
+recent	O
+climate	O
+observations	O
+.	O
+
+Frequency	O
+of	O
+seeing	O
+curves	O
+were	O
+examined	O
+for	O
+the	O
+method	O
+most	O
+similar	O
+to	O
+FDT	O
+.	O
+
+Chronic	O
+graft	O
+-	O
+versus	O
+-	O
+host	O
+disease	O
+(	O
+cGVHD	O
+)	O
+is	O
+a	O
+major	O
+complication	O
+of	O
+allogeneic	O
+hematopoietic	O
+cell	O
+transplantation	O
+.	O
+
+Compared	O
+to	O
+white	O
+-	O
+on	O
+-	O
+white	O
+(	O
+W	O
+-	O
+W	O
+)	O
+perimetry	O
+,	O
+SWAP	O
+is	O
+limited	O
+clinically	O
+by	O
+:	O
+greater	O
+variability	O
+associated	O
+with	O
+the	O
+estimation	O
+of	O
+threshold	O
+,	O
+ocular	O
+media	O
+absorption	O
+,	O
+increased	O
+examination	O
+duration	O
+and	O
+an	O
+additional	O
+learning	O
+effect	O
+.	O
+
+Preservatives	O
+are	O
+an	O
+important	O
+component	O
+of	O
+ophthalmic	O
+preparations	O
+,	O
+providing	O
+antimicrobial	O
+activity	O
+in	O
+the	O
+bottle	O
+and	O
+preventing	O
+decomposition	O
+of	O
+active	O
+drug	O
+.	O
+
+Comparative	O
+analysis	O
+of	O
+various	O
+techniques	O
+of	O
+prostatic	O
+drainage	O
+in	O
+patients	O
+with	O
+chronic	O
+obstructive	O
+prostatitis	O
+]	O
+The	O
+efficacy	O
+of	O
+prostatic	O
+drainage	O
+using	O
+transurethral	O
+vacuum	O
+aspiration	O
+(	O
+Introl	O
+-	O
+4	O
+unit	O
+)	O
+and	O
+transrectal	O
+pneumovibromassage	O
+(	O
+PVM	O
+-	O
+R	O
+-	O
+01	O
+)	O
+was	O
+compared	O
+in	O
+1511	O
+patients	O
+with	O
+chronic	O
+obstructive	O
+prostatitis	O
+.	O
+
+Consumption	O
+of	O
+4	O
+%	O
+sucrose	O
+was	O
+not	O
+affected	O
+by	O
+excitotoxic	O
+lesions	O
+of	O
+the	O
+PPTg	O
+,	O
+but	O
+PPTg	O
+lesioned	O
+rats	O
+consumed	O
+significantly	O
+more	O
+12	O
+%	O
+and	O
+20	O
+%	O
+sucrose	O
+than	O
+sham	O
+controls	O
+.	O
+
+Actuarial	O
+freedom	O
+from	O
+ventricular	O
+arrhythmias	O
+at	O
+4	O
+-	O
+year	O
+follow	O
+-	O
+up	O
+was	O
+74	O
+.	O
+1	O
++	O
+/	O
+-	O
+6	O
+.	O
+0	O
+%	O
+in	O
+group	O
+A	O
+vs	O
+.	O
+
+Mental	O
+development	O
+is	O
+generally	O
+normal	O
+.	O
+
+Influence	O
+of	O
+different	O
+methods	O
+of	O
+chemical	O
+disinfection	O
+on	O
+the	O
+physical	O
+properties	O
+of	O
+type	O
+IV	O
+and	O
+V	O
+gypsum	O
+dies	O
+]	O
+Several	O
+instruments	O
+and	O
+materials	O
+frequently	O
+used	O
+in	O
+prosthodontics	O
+-	O
+-	O
+such	O
+as	O
+stone	O
+casts	O
+,	O
+dental	O
+impressions	O
+,	O
+interocclusal	O
+records	O
+-	O
+-	O
+are	O
+classified	O
+,	O
+by	O
+the	O
+dental	O
+literature	O
+,	O
+as	O
+vehicles	O
+of	O
+transmission	O
+of	O
+infectious	O
+diseases	O
+to	O
+those	O
+who	O
+handle	O
+them	O
+.	O
+
+Vitrectomy	O
+and	O
+removal	O
+of	O
+retained	O
+lens	O
+fragments	O
+restores	O
+good	O
+visual	O
+acuity	O
+and	O
+reduces	O
+secondary	O
+glaucoma	O
+in	O
+the	O
+majority	O
+of	O
+patients	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+mechanism	O
+of	O
+MIRI	O
+is	O
+Qi	O
+deficiency	O
+and	O
+blood	O
+stasis	O
+in	O
+TCM	O
+,	O
+its	O
+treating	O
+principles	O
+should	O
+be	O
+promoting	O
+Qi	O
+and	O
+removing	O
+the	O
+blood	O
+stasis	O
+.	O
+
+Effects	O
+of	O
+activating	O
+blood	O
+circulation	O
+to	O
+remove	O
+blood	O
+stasis	O
+on	O
+barrier	O
+action	O
+of	O
+gastric	O
+wall	O
+in	O
+chronic	O
+atrophic	O
+gastritis	O
+
+Proteomic	O
+patterns	O
+of	O
+nipple	O
+aspirate	O
+fluids	O
+obtained	O
+by	O
+SELDI	O
+-	O
+TOF	O
+:	O
+potential	O
+for	O
+new	O
+biomarkers	O
+to	O
+aid	O
+in	O
+the	O
+diagnosis	O
+of	O
+breast	O
+cancer	O
+.	O
+
+According	O
+to	O
+the	O
+laboratory	O
+results	O
+,	O
+the	O
+application	O
+of	O
+neural	O
+network	O
+can	O
+solve	O
+the	O
+problem	O
+successfully	O
+.	O
+
+A	O
+high	O
+-	O
+efficiency	O
+cross	O
+-	O
+flow	O
+micronebulizer	O
+interface	O
+for	O
+capillary	O
+electrophoresis	O
+and	O
+inductively	O
+coupled	O
+plasma	O
+mass	O
+spectrometry	O
+.	O
+
+The	O
+experimental	O
+results	O
+showed	O
+that	O
+the	O
+coagulation	O
+-	O
+electrooxidation	O
+process	O
+could	O
+efficiently	O
+remove	O
+the	O
+color	O
+and	O
+the	O
+COD	O
+from	O
+the	O
+simulated	O
+dye	O
+wastewater	O
+.	O
+
+Cyclic	O
+loading	O
+of	O
+bone	O
+during	O
+normal	O
+daily	O
+activity	O
+leads	O
+to	O
+the	O
+formation	O
+of	O
+microcracks	O
+within	O
+the	O
+tissue	O
+matrix	O
+of	O
+compact	O
+bone	O
+.	O
+
+The	O
+weight	O
+-	O
+bearing	O
+surface	O
+of	O
+the	O
+PE	O
+head	O
+became	O
+smoother	O
+with	O
+time	O
+after	O
+THA	O
+,	O
+and	O
+the	O
+friction	O
+coefficient	O
+did	O
+not	O
+differ	O
+significantly	O
+from	O
+that	O
+of	O
+an	O
+unused	O
+PE	O
+head	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+demonstrate	O
+a	O
+lack	O
+of	O
+effect	O
+of	O
+steady	O
+-	O
+state	O
+concentrations	O
+of	O
+cilomilast	O
+,	O
+a	O
+new	O
+oral	O
+phosphodiesterase	B-GENE
+4	I-GENE
+inhibitor	O
+for	O
+the	O
+treatment	O
+of	O
+chronic	O
+obstructive	O
+pulmonary	O
+disease	O
+,	O
+on	O
+warfarin	O
+-	O
+induced	O
+anticoagulation	O
+.	O
+
+Postdocs	O
+face	O
+hardship	O
+across	O
+mainland	O
+Europe	O
+.	O
+
+The	O
+design	O
+principle	O
+based	O
+on	O
+a	O
+uniform	O
+vibration	O
+mode	O
+is	O
+presented	O
+.	O
+
+Dynamic	O
+imaging	O
+of	O
+nuclear	O
+wave	O
+functions	O
+with	O
+ultrashort	O
+UV	O
+laser	O
+pulses	O
+.	O
+
+Efficacy	O
+and	O
+safety	O
+of	O
+aspirin	O
+in	O
+the	O
+long	O
+-	O
+term	O
+management	O
+of	O
+atherothrombosis	O
+.	O
+
+The	O
+General	O
+Practice	O
+Research	O
+Database	O
+(	O
+GPRD	O
+)	O
+is	O
+the	O
+world	O
+'	O
+s	O
+largest	O
+computerized	O
+database	O
+of	O
+anonymized	O
+longitudinal	O
+patient	O
+records	O
+from	O
+general	O
+practice	O
+and	O
+is	O
+a	O
+unique	O
+public	O
+health	O
+research	O
+tool	O
+.	O
+
+This	O
+paper	O
+reports	O
+the	O
+results	O
+of	O
+a	O
+laboratory	O
+study	O
+on	O
+aldicarb	O
+and	O
+its	O
+main	O
+metabolites	O
+,	O
+aldicarb	O
+sulfone	O
+and	O
+aldicarb	O
+sulfoxide	O
+.	O
+
+Only	O
+one	O
+DC	O
+cardioversion	O
+was	O
+required	O
+in	O
+the	O
+HBS	O
+group	O
+,	O
+whereas	O
+2	O
+DC	O
+in	O
+the	O
+CBC	O
+group	O
+and	O
+total	O
+7	O
+DC	O
+in	O
+the	O
+GIK	O
+group	O
+.	O
+
+Since	O
+August	O
+1994	O
+,	O
+the	O
+ENRP	O
+has	O
+retained	O
+70	O
+.	O
+3	O
+metric	O
+tons	O
+of	O
+TP	O
+that	O
+otherwise	O
+would	O
+have	O
+entered	O
+the	O
+Everglades	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+the	O
+disappearance	O
+of	O
+BOD5	O
+and	O
+NH3	O
+-	O
+N	O
+could	O
+be	O
+approximated	O
+using	O
+first	O
+-	O
+order	O
+kinetics	O
+,	O
+but	O
+the	O
+kinetics	O
+of	O
+TP	O
+removal	O
+were	O
+unclear	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+the	O
+disappearance	O
+of	O
+BOD5	O
+and	O
+NH3	O
+-	O
+N	O
+could	O
+be	O
+approximated	O
+using	O
+first	O
+-	O
+order	O
+kinetics	O
+,	O
+but	O
+the	O
+kinetics	O
+of	O
+TP	O
+removal	O
+were	O
+unclear	O
+.	O
+
+Losses	O
+of	O
+dichlofluanid	O
+(	O
+54	O
+%	O
+)	O
+,	O
+chlozolinate	O
+(	O
+22	O
+%	O
+)	O
+,	O
+and	O
+etridiazole	O
+(	O
+40	O
+%	O
+)	O
+,	O
+previously	O
+reported	O
+to	O
+occur	O
+during	O
+ambient	O
+processing	O
+of	O
+apples	O
+,	O
+were	O
+reduced	O
+to	O
+barely	O
+significant	O
+levels	O
+(	O
+10	O
+,	O
+17	O
+,	O
+and	O
+14	O
+%	O
+,	O
+respectively	O
+)	O
+by	O
+cryogenic	O
+processing	O
+.	O
+
+The	O
+TB	O
+incidence	O
+in	O
+the	O
+"	O
+AIRIN	O
+"	O
+area	O
+,	O
+where	O
+about	O
+20	O
+%	O
+TB	O
+patients	O
+are	O
+homeless	O
+,	O
+shows	O
+highest	O
+rate	O
+of	O
+above	O
+1	O
+,	O
+000	O
+/	O
+100	O
+,	O
+000	O
+.	O
+
+It	O
+is	O
+shown	O
+that	O
+the	O
+displacement	O
+distribution	O
+measured	O
+by	O
+q	O
+-	O
+space	O
+MRI	O
+in	O
+both	O
+the	O
+large	O
+displacement	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+large	O
+r	O
+)	O
+and	O
+the	O
+long	O
+-	O
+wavelength	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+small	O
+q	O
+)	O
+limits	O
+is	O
+the	O
+same	O
+3D	O
+Gaussian	O
+displacement	O
+distribution	O
+assumed	O
+in	O
+DT	O
+-	O
+MRI	O
+.	O
+
+The	O
+procedure	O
+facilitated	O
+the	O
+retention	O
+of	O
+a	O
+mandibular	O
+molar	O
+with	O
+a	O
+Class	O
+III	O
+FI	O
+in	O
+a	O
+manner	O
+acceptable	O
+to	O
+both	O
+the	O
+patient	O
+and	O
+the	O
+clinician	O
+.	O
+
+The	O
+results	O
+of	O
+our	O
+ten	O
+-	O
+fold	O
+cross	O
+-	O
+validation	O
+experiments	O
+show	O
+that	O
+,	O
+on	O
+the	O
+average	O
+,	O
+the	O
+system	O
+increases	O
+the	O
+specificity	O
+from	O
+0	O
+.	O
+19	O
+(	O
+0	O
+.	O
+35	O
+)	O
+to	O
+0	O
+.	O
+69	O
+(	O
+0	O
+.	O
+74	O
+)	O
+at	O
+a	O
+sensitivity	O
+level	O
+of	O
+1	O
+.	O
+0	O
+(	O
+0	O
+.	O
+95	O
+)	O
+.	O
+
+The	O
+physical	O
+characteristics	O
+of	O
+these	O
+calls	O
+vary	O
+among	O
+species	O
+of	O
+bat	O
+,	O
+and	O
+variations	O
+also	O
+exist	O
+in	O
+the	O
+timing	O
+and	O
+patterns	O
+of	O
+respiratory	O
+muscle	O
+recruitment	O
+during	O
+echolocation	O
+.	O
+
+Clicking	O
+on	O
+"	O
+Examples	O
+and	O
+Explanations	O
+of	O
+APA	O
+Form	O
+"	O
+provides	O
+a	O
+help	O
+system	O
+with	O
+examples	O
+of	O
+the	O
+various	O
+sections	O
+of	O
+a	O
+review	O
+article	O
+,	O
+journal	O
+article	O
+that	O
+has	O
+one	O
+experiment	O
+,	O
+or	O
+journal	O
+article	O
+that	O
+has	O
+two	O
+or	O
+more	O
+experiments	O
+.	O
+
+The	O
+drug	O
+packets	O
+contained	O
+acetyl	O
+aspirin	O
+,	O
+acetaminophen	O
+and	O
+chloramphenicol	O
+.	O
+
+Karger	O
+AG	O
+,	O
+Basel	O
+
+AIM	O
+:	O
+To	O
+understand	O
+the	O
+role	O
+of	O
+nutritional	O
+status	O
+in	O
+cirrhotic	O
+patients	O
+without	O
+clinical	O
+porto	O
+-	O
+systemic	O
+encephalopathy	O
+(	O
+PSE	O
+)	O
+.	O
+METHODS	O
+:	O
+Fifty	O
+-	O
+one	O
+non	O
+-	O
+alcoholic	O
+patients	O
+with	O
+cirrhosis	O
+without	O
+PSE	O
+were	O
+studied	O
+prospectively	O
+and	O
+compared	O
+with	O
+20	O
+healthy	O
+volunteers	O
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURE	O
+(	O
+S	O
+)	O
+:	O
+Serum	O
+levels	O
+of	O
+FSH	B-GENE
+,	O
+LH	B-GENE
+,	O
+and	O
+inhibin	B-GENE
+A	I-GENE
+and	I-GENE
+B	I-GENE
+.	O
+
+For	O
+instance	O
+,	O
+a	O
+total	O
+SIP	O
+score	O
+of	O
+an	O
+individual	O
+patient	O
+of	O
+28	O
+.	O
+3	O
+%	O
+(	O
+which	O
+is	O
+taken	O
+as	O
+an	O
+example	O
+,	O
+being	O
+the	O
+mean	O
+score	O
+in	O
+the	O
+study	O
+population	O
+)	O
+should	O
+decrease	O
+by	O
+at	O
+least	O
+9	O
+.	O
+26	O
+%	O
+or	O
+approximately	O
+13	O
+items	O
+,	O
+before	O
+any	O
+improvement	O
+beyond	O
+reproducibility	O
+noise	O
+can	O
+be	O
+detected	O
+.	O
+
+Group	O
+I	O
+comprised	O
+5	O
+adult	O
+Collies	O
+that	O
+received	O
+at	O
+least	O
+400	O
+microg	O
+/	O
+kg	O
+ivermectin	O
+p	O
+.	O
+o	O
+.	O
+and	O
+were	O
+presented	O
+to	O
+the	O
+VMTH	O
+3	O
+hours	O
+after	O
+intoxication	O
+.	O
+
+No	O
+increased	O
+tumor	O
+-	O
+related	O
+mortality	O
+was	O
+observed	O
+after	O
+a	O
+mean	O
+follow	O
+-	O
+up	O
+of	O
+44	O
+months	O
+.	O
+
+Dissociable	O
+effects	O
+of	O
+lidocaine	O
+inactivation	O
+of	O
+the	O
+rostral	O
+and	O
+caudal	O
+basolateral	O
+amygdala	O
+on	O
+the	O
+maintenance	O
+and	O
+reinstatement	O
+of	O
+cocaine	O
+-	O
+seeking	O
+behavior	O
+in	O
+rats	O
+.	O
+
+The	O
+population	O
+studied	O
+comprised	O
+4472	O
+men	O
+and	O
+5212	O
+women	O
+aged	O
+30	O
+-	O
+74	O
+years	O
+,	O
+without	O
+coronary	O
+heart	O
+disease	O
+,	O
+who	O
+had	O
+CRP	B-GENE
+measurements	O
+in	O
+the	O
+Third	O
+National	O
+Health	O
+and	O
+Nutrition	O
+Examination	O
+Survey	O
+(	O
+NHANES	O
+III	O
+)	O
+.	O
+
+Herceptin	O
+,	O
+which	O
+recognizes	O
+the	O
+HER	B-GENE
+-	I-GENE
+2	I-GENE
+/	O
+neu	B-GENE
+antigen	O
+and	O
+has	O
+similar	O
+size	O
+(	O
+10	O
+nm	O
+)	O
+to	O
+G6	O
+-	O
+(	O
+1B4M	O
+-	O
+Gd	O
+)	O
+(	O
+256	O
+)	O
+,	O
+accumulated	O
+and	O
+internalized	O
+in	O
+the	O
+WIBC	O
+-	O
+9	O
+tumors	O
+more	O
+quickly	O
+than	O
+in	O
+the	O
+control	O
+MC	O
+-	O
+5	O
+tumors	O
+that	O
+progress	O
+with	O
+normal	O
+angiogenesis	O
+.	O
+
+Forty	O
+-	O
+eight	O
+pigs	O
+were	O
+removed	O
+from	O
+sows	O
+at	O
+1	O
+d	O
+of	O
+age	O
+and	O
+randomly	O
+assigned	O
+to	O
+one	O
+of	O
+three	O
+treatments	O
+:	O
+1	O
+)	O
+control	O
+with	O
+lactose	O
+as	O
+the	O
+carbohydrate	O
+source	O
+,	O
+2	O
+)	O
+lactose	O
+replaced	O
+(	O
+gram	O
+for	O
+gram	O
+)	O
+with	O
+CSS	O
+(	O
+dextrose	O
+equivalent	O
+[	O
+DE	O
+]	O
+-	O
+20	O
+)	O
+,	O
+and	O
+3	O
+)	O
+lactose	O
+replaced	O
+with	O
+DE	O
+-	O
+42	O
+.	O
+
+CONCLUSIONS	O
+:	O
+AMVT	O
+is	O
+rare	O
+but	O
+a	O
+potentially	O
+lethal	O
+emergency	O
+disease	O
+.	O
+
+Therefore	O
+,	O
+in	O
+a	O
+large	O
+animal	O
+model	O
+of	O
+permanent	O
+focal	O
+ischemia	O
+in	O
+which	O
+transfusion	O
+starts	O
+30	O
+min	O
+after	O
+ischemia	O
+,	O
+tetrameric	O
+cross	O
+-	O
+linked	O
+hemoglobin	B-GENE
+transfusion	O
+can	O
+augment	O
+oxygen	O
+transport	O
+to	O
+the	O
+ischemic	O
+cortex	O
+,	O
+but	O
+the	O
+increase	O
+can	O
+be	O
+delayed	O
+and	O
+not	O
+necessarily	O
+provide	O
+protection	O
+.	O
+
+Since	O
+the	O
+early	O
+1980s	O
+there	O
+has	O
+been	O
+increasing	O
+awareness	O
+of	O
+the	O
+importance	O
+of	O
+quantifying	O
+health	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+(	O
+HRQL	O
+)	O
+in	O
+patients	O
+with	O
+chronic	O
+respiratory	O
+disorders	O
+included	O
+in	O
+clinical	O
+trials	O
+.	O
+
+They	O
+were	O
+randomly	O
+allocated	O
+to	O
+receive	O
+either	O
+625	O
+mg	O
+of	O
+calcium	O
+carbonate	O
+(	O
+250	O
+mg	O
+of	O
+elemental	O
+calcium	O
+)	O
+at	O
+the	O
+end	O
+of	O
+a	O
+meal	O
+three	O
+times	O
+a	O
+day	O
+(	O
+group	O
+A	O
+,	O
+n	O
+=	O
+26	O
+)	O
+or	O
+calcium	O
+carbonate	O
+in	O
+the	O
+same	O
+manner	O
+plus	O
+0	O
+.	O
+625	O
+mg	O
+/	O
+day	O
+of	O
+conjugated	O
+equine	O
+estrogen	O
+and	O
+5	O
+mg	O
+medrogestone	O
+acetate	O
+from	O
+day	O
+1	O
+-	O
+12	O
+each	O
+month	O
+(	O
+group	O
+B	O
+,	O
+n	O
+=	O
+30	O
+)	O
+.	O
+
+The	O
+two	O
+-	O
+wave	O
+,	O
+1995	O
+-	O
+1996	O
+National	O
+Longitudinal	O
+Study	O
+of	O
+Adolescent	O
+Health	O
+uses	O
+a	O
+measure	O
+of	O
+depressive	O
+symptomatology	O
+across	O
+a	O
+12	O
+-	O
+month	O
+interval	O
+.	O
+
+METHODS	O
+:	O
+9	O
+cases	O
+of	O
+conventional	O
+intermittent	O
+tissue	O
+expansion	O
+(	O
+CITE	O
+)	O
+and	O
+9	O
+cases	O
+of	O
+continuous	O
+pressure	O
+-	O
+controlled	O
+tissue	O
+expansion	O
+(	O
+CPTE	O
+)	O
+were	O
+chosen	O
+for	O
+the	O
+study	O
+.	O
+
+Wegener	O
+'	O
+s	O
+granulomatosis	O
+
+There	O
+was	O
+a	O
+significant	O
+effect	O
+of	O
+hematocrit	O
+on	O
+the	O
+General	O
+Health	O
+scale	O
+on	O
+the	O
+SF	O
+-	O
+36	O
+(	O
+P	O
+=	O
+0	O
+.	O
+03	O
+)	O
+.	O
+
+A	O
+global	O
+response	O
+rate	O
+was	O
+17	O
+%	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+(	O
+95	O
+%	O
+CI	O
+)	O
+:	O
+2	O
+%	O
+-	O
+32	O
+%	O
+)	O
+and	O
+the	O
+median	O
+overall	O
+survival	O
+was	O
+12	O
+months	O
+.	O
+
+We	O
+also	O
+studied	O
+a	O
+new	O
+parameter	O
+:	O
+the	O
+angle	O
+to	O
+maximal	O
+peak	O
+torque	O
+(	O
+APT	O
+)	O
+.	O
+
+For	O
+the	O
+2	O
+.	O
+5	O
+to	O
+4	O
+ng	O
+/	O
+mL	O
+model	O
+,	O
+the	O
+AUC	O
+of	O
+the	O
+ANN	O
+ROC	O
+curve	O
+was	O
+significantly	O
+higher	O
+than	O
+the	O
+AUCs	O
+for	O
+percentage	O
+of	O
+free	O
+PSA	B-GENE
+(	O
+P	O
+=	O
+.	O
+0239	O
+)	O
+,	O
+PSA	O
+-	O
+TZ	O
+(	O
+P	O
+=	O
+.	O
+0204	O
+)	O
+,	O
+and	O
+PSA	B-GENE
+density	O
+and	O
+total	O
+prostate	O
+volume	O
+(	O
+P	O
+<	O
+.	O
+01	O
+for	O
+both	O
+)	O
+.	O
+
+Potential	O
+treatments	O
+include	O
+dobutamine	O
+,	O
+KATP	O
+channel	O
+activators	O
+,	O
+and	O
+21	O
+-	O
+aminosteroids	O
+.	O
+
+Selenium	O
+is	O
+an	O
+essential	O
+element	O
+for	O
+humans	O
+,	O
+animals	O
+and	O
+some	O
+species	O
+of	O
+microorganisms	O
+.	O
+
+The	O
+GT	O
+-	O
+foreign	O
+-	O
+pictures	O
+showed	O
+that	O
+the	O
+judgment	O
+of	O
+other	O
+subjects	O
+changed	O
+toward	O
+hedonic	O
+and	O
+permeability	O
+directions	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+target	O
+dose	O
+was	O
+comparable	O
+in	O
+the	O
+3D	O
+-	O
+CRT	O
+and	O
+IMRT	O
+plans	O
+,	O
+although	O
+improvements	O
+were	O
+seen	O
+when	O
+seven	O
+and	O
+nine	O
+IMRT	O
+fields	O
+were	O
+used	O
+.	O
+
+We	O
+therefore	O
+applied	O
+a	O
+radiolabelled	O
+serumalbumin	B-GENE
+method	O
+to	O
+determine	O
+blood	O
+volume	O
+after	O
+haemodilution	O
+with	O
+crosslinked	O
+or	O
+conjugated	O
+haemoglobin	B-GENE
+,	O
+in	O
+comparison	O
+with	O
+a	O
+reference	O
+solution	O
+of	O
+hydroxyethyl	O
+starch	O
+(	O
+HES	O
+)	O
+.	O
+
+The	O
+equilibrium	O
+phosphorus	O
+content	O
+(	O
+EPC0	O
+)	O
+of	O
+surface	O
+soil	O
+was	O
+generally	O
+higher	O
+than	O
+the	O
+SRP	O
+content	O
+of	O
+drainage	O
+water	O
+,	O
+at	O
+one	O
+farm	O
+by	O
+1	O
+order	O
+of	O
+magnitude	O
+.	O
+
+The	O
+long	O
+-	O
+term	O
+prediction	O
+is	O
+based	O
+on	O
+an	O
+algorithm	O
+for	O
+R	O
+-	O
+R	O
+interval	O
+estimation	O
+.	O
+
+Despite	O
+considerable	O
+research	O
+,	O
+an	O
+explanation	O
+of	O
+this	O
+effect	O
+has	O
+been	O
+elusive	O
+.	O
+
+The	O
+structure	O
+has	O
+been	O
+established	O
+by	O
+a	O
+study	O
+of	O
+its	O
+mono	O
+-	O
+and	O
+bidimensional	O
+NMR	O
+spectra	O
+and	O
+mass	O
+spectrometry	O
+.	O
+
+We	O
+argue	O
+that	O
+this	O
+is	O
+the	O
+general	O
+property	O
+of	O
+QSAR	O
+models	O
+developed	O
+using	O
+LOO	O
+cross	O
+-	O
+validation	O
+.	O
+
+We	O
+compared	O
+the	O
+efficacy	O
+and	O
+costs	O
+of	O
+valacyclovir	O
+in	O
+preventing	O
+HSV	O
+reactivation	O
+among	O
+HSV	O
+seropositive	O
+autologous	O
+progenitor	O
+cell	O
+transplantation	O
+(	O
+APCT	O
+)	O
+patients	O
+with	O
+historical	O
+controls	O
+in	O
+whom	O
+intravenous	O
+acyclovir	O
+or	O
+no	O
+HSV	O
+prophylaxis	O
+were	O
+used	O
+.	O
+
+All	O
+adults	O
+attending	O
+the	O
+outpatient	O
+clinics	O
+of	O
+a	O
+dermatological	O
+hospital	O
+on	O
+predetermined	O
+days	O
+were	O
+given	O
+the	O
+12	O
+-	O
+item	O
+General	O
+Health	O
+Questionnaire	O
+.	O
+
+Data	O
+on	O
+prosthesis	O
+use	O
+are	O
+encouraging	O
+,	O
+although	O
+a	O
+follow	O
+-	O
+up	O
+study	O
+is	O
+required	O
+to	O
+determine	O
+the	O
+functional	O
+outcome	O
+for	O
+prosthesis	O
+users	O
+and	O
+non	O
+-	O
+users	O
+.	O
+
+A	O
+mail	O
+survey	O
+of	O
+Georgia	O
+members	O
+of	O
+the	O
+American	O
+College	O
+of	O
+Obstetricians	O
+and	O
+Gynecologists	O
+was	O
+conducted	O
+.	O
+
+HIV	O
+-	O
+1	O
+C	O
+subtype	O
+in	O
+IDUs	O
+accounted	O
+for	O
+61	O
+.	O
+3	O
+%	O
+.	O
+
+When	O
+a	O
+plateau	O
+of	O
+enhancement	O
+was	O
+reached	O
+,	O
+a	O
+single	O
+lesion	O
+in	O
+each	O
+patient	O
+was	O
+imaged	O
+using	O
+five	O
+different	O
+continuous	O
+scanning	O
+modes	O
+,	O
+fundamental	O
+grey	O
+scale	O
+(	O
+FGS	O
+)	O
+;	O
+fundamental	O
+colour	O
+Doppler	O
+(	O
+FCD	O
+)	O
+;	O
+fundamental	O
+power	O
+Doppler	O
+(	O
+FPD	O
+)	O
+;	O
+second	O
+harmonic	O
+grey	O
+scale	O
+(	O
+HGS	O
+)	O
+;	O
+and	O
+pulse	O
+inversion	O
+mode	O
+(	O
+Pim	O
+)	O
+using	O
+an	O
+HDI5000	O
+scanner	O
+and	O
+C5	O
+-	O
+2	O
+probe	O
+(	O
+ATL	O
+,	O
+Bothell	O
+,	O
+WA	O
+)	O
+.	O
+
+A	O
+comparative	O
+study	O
+of	O
+the	O
+effects	O
+of	O
+carbamazepine	O
+and	O
+the	O
+NMDA	B-GENE
+receptor	I-GENE
+antagonist	O
+remacemide	O
+on	O
+road	O
+tracking	O
+and	O
+car	O
+-	O
+following	O
+performance	O
+in	O
+actual	O
+traffic	O
+.	O
+
+We	O
+find	O
+that	O
+the	O
+measured	O
+Nusselt	O
+number	O
+decreased	O
+about	O
+20	O
+%	O
+over	O
+the	O
+range	O
+of	O
+Pr	O
+spanned	O
+in	O
+the	O
+experiment	O
+.	O
+
+Viral	O
+and	O
+atypical	O
+pathogens	O
+as	O
+causes	O
+of	O
+type	O
+1	O
+acute	O
+exacerbations	O
+of	O
+chronic	O
+bronchitis	O
+.	O
+
+Treatment	O
+for	O
+this	O
+condition	O
+often	O
+involves	O
+use	O
+of	O
+a	O
+wax	O
+softening	O
+or	O
+dispersing	O
+agent	O
+(	O
+cerumenolytic	O
+)	O
+before	O
+syringing	O
+.	O
+
+In	O
+addition	O
+,	O
+benzocaine	O
+and	O
+2	O
+-	O
+phenoxyethanol	O
+depressed	O
+complement	O
+activity	O
+and	O
+phagocytosis	O
+,	O
+while	O
+MS222	O
+and	O
+quinaldine	O
+sulphate	O
+did	O
+not	O
+.	O
+
+The	O
+EC	O
+(	O
+50	O
+)	O
+for	O
+suppression	O
+of	O
+long	O
+-	O
+term	O
+memory	O
+(	O
+the	O
+concentration	O
+decreasing	O
+memory	O
+by	O
+50	O
+%	O
+)	O
+of	O
+fear	O
+conditioning	O
+to	O
+context	O
+was	O
+2	O
+.	O
+00	O
+%	O
+plus	O
+/	O
+minus	O
+0	O
+.	O
+01	O
+%	O
+(	O
+mean	O
+plus	O
+/	O
+minus	O
+SEM	O
+)	O
+,	O
+and	O
+for	O
+fear	O
+conditioning	O
+to	O
+tone	O
+was	O
+3	O
+.	O
+45	O
+%	O
+plus	O
+/	O
+minus	O
+0	O
+.	O
+26	O
+%	O
+,	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+It	O
+has	O
+been	O
+proposed	O
+that	O
+insulin	B-GENE
+resistance	O
+(	O
+IR	O
+)	O
+underlies	O
+a	O
+cluster	O
+of	O
+cardiovascular	O
+disease	O
+(	O
+CVD	O
+)	O
+risk	O
+factors	O
+constituting	O
+a	O
+"	O
+metabolic	O
+syndrome	O
+.	O
+"	O
+CVD	O
+is	O
+a	O
+leading	O
+cause	O
+of	O
+premature	O
+mortality	O
+among	O
+indigenous	O
+Australians	O
+.	O
+
+Dementia	O
+is	O
+being	O
+avoided	O
+in	O
+NHS	O
+and	O
+social	O
+care	O
+.	O
+
+HIV	O
+-	O
+1	O
+infection	O
+in	O
+rural	O
+Africa	O
+:	O
+is	O
+there	O
+a	O
+difference	O
+in	O
+median	O
+time	O
+to	O
+AIDS	O
+and	O
+survival	O
+compared	O
+with	O
+that	O
+in	O
+industrialized	O
+countries	O
+?	O
+OBJECTIVES	O
+:	O
+To	O
+describe	O
+the	O
+progression	O
+times	O
+of	O
+HIV	O
+-	O
+1	O
+infection	O
+from	O
+seroconversion	O
+to	O
+AIDS	O
+and	O
+to	O
+death	O
+,	O
+and	O
+time	O
+from	O
+first	O
+developing	O
+AIDS	O
+to	O
+death	O
+in	O
+rural	O
+Uganda	O
+.	O
+
+The	O
+use	O
+of	O
+highly	O
+active	O
+antiretroviral	O
+therapy	O
+(	O
+HAART	O
+)	O
+has	O
+resulted	O
+in	O
+significant	O
+improvements	O
+in	O
+the	O
+treatment	O
+of	O
+HIV	O
+infection	O
+,	O
+including	O
+a	O
+decrease	O
+in	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+several	O
+acquired	O
+immune	O
+deficiency	O
+syndrome	O
+(	O
+AIDS	O
+)	O
+-	O
+related	O
+malignancies	O
+.	O
+
+Time	O
+to	O
+progression	O
+was	O
+6	O
+months	O
+(	O
+5	O
+-	O
+7	O
+months	O
+)	O
+with	O
+a	O
+median	O
+survival	O
+from	O
+registration	O
+of	O
+9	O
+.	O
+6	O
+months	O
+(	O
+95	O
+%	O
+CI	O
+8	O
+-	O
+12	O
+months	O
+)	O
+.	O
+
+Heparin	O
+(	O
+100	O
+U	O
+.	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+.	O
+day	O
+(	O
+-	O
+1	O
+)	O
+)	O
+was	O
+injected	O
+subcutaneously	O
+to	O
+the	O
+rats	O
+in	O
+H	O
+group	O
+while	O
+normal	O
+saline	O
+to	O
+those	O
+in	O
+N	O
+group	O
+once	O
+a	O
+day	O
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURE	O
+:	O
+A	O
+positive	O
+test	O
+result	O
+for	O
+gonococcal	O
+or	O
+chlamydial	O
+infection	O
+by	O
+the	O
+ligase	B-GENE
+chain	O
+reaction	O
+assay	O
+;	O
+secondary	O
+outcome	O
+measure	O
+was	O
+a	O
+positive	O
+test	O
+result	O
+for	O
+human	O
+immunodeficiency	O
+virus	O
+(	O
+HIV	O
+)	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+develop	O
+a	O
+reliable	O
+and	O
+culturally	O
+meaningful	O
+exercise	O
+self	O
+-	O
+efficacy	O
+questionnaire	O
+for	O
+older	O
+Mexican	O
+American	O
+women	O
+.	O
+
+Neutrophil	O
+:	O
+lymphocyte	O
+ratio	O
+,	O
+plasma	O
+haptoglobin	B-GENE
+,	O
+and	O
+CBG	B-GENE
+levels	O
+were	O
+greater	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+during	O
+the	O
+INITIAL	O
+period	O
+than	O
+during	O
+the	O
+PRE	O
+or	O
+POST	O
+periods	O
+but	O
+did	O
+not	O
+differ	O
+between	O
+treatments	O
+.	O
+
+CD	O
+was	O
+determined	O
+using	O
+the	O
+Farnsworth	O
+D	O
+-	O
+15	O
+method	O
+.	O
+
+Here	O
+is	O
+presented	O
+the	O
+monitoring	O
+of	O
+the	O
+accidental	O
+spill	O
+on	O
+vertical	O
+distribution	O
+of	O
+heavy	O
+metals	O
+in	O
+the	O
+estuarine	O
+sediments	O
+.	O
+
+The	O
+large	O
+fluxes	O
+of	O
+239	O
++	O
+240Pu	O
+might	O
+be	O
+attributed	O
+to	O
+episodic	O
+lateral	O
+transport	O
+of	O
+particles	O
+that	O
+flow	O
+down	O
+the	O
+continental	O
+slope	O
+with	O
+the	O
+nepheloid	O
+layer	O
+which	O
+was	O
+considered	O
+to	O
+be	O
+significant	O
+for	O
+239	O
++	O
+240Pu	O
+transport	O
+on	O
+the	O
+continental	O
+slope	O
+in	O
+the	O
+East	O
+China	O
+Sea	O
+.	O
+
+Rigorous	O
+treatment	O
+protocols	O
+for	O
+diet	O
+delivery	O
+and	O
+EEN	O
+-	O
+related	O
+GI	O
+adverse	O
+effects	O
+were	O
+applied	O
+.	O
+
+The	O
+range	O
+of	O
+200	O
+000	O
+-	O
+300	O
+000	O
+spermatozoa	O
+/	O
+microl	O
+appeared	O
+to	O
+be	O
+a	O
+reasonable	O
+compromise	O
+for	O
+both	O
+criteria	O
+.	O
+
+Gastritis	O
+score	O
+was	O
+significantly	O
+lower	O
+in	O
+nod	O
+-	O
+/	O
+CagA	B-GENE
+-	O
+children	O
+than	O
+in	O
+nod	O
++	O
+/	O
+CagA	B-GENE
+-	O
+(	O
+p	O
+=	O
+.	O
+004	O
+)	O
+,	O
+nod	O
+-	O
+/	O
+CagA	B-GENE
++	O
+(	O
+p	O
+=	O
+.	O
+002	O
+)	O
+and	O
+nod	O
++	O
+/	O
+CagA	B-GENE
++	O
+(	O
+p	O
+<	O
+.	O
+001	O
+)	O
+,	O
+both	O
+in	O
+the	O
+antrum	O
+and	O
+corpus	O
+.	O
+
+The	O
+mean	O
+thickness	O
+of	O
+the	O
+visceral	O
+peritoneum	O
+was	O
+comparable	O
+in	O
+both	O
+groups	O
+of	O
+animals	O
+,	O
+but	O
+,	O
+macroscopically	O
+,	O
+more	O
+severe	O
+fibrosis	O
+was	O
+found	O
+in	O
+the	O
+peritoneum	O
+of	O
+rats	O
+exposed	O
+to	O
+CAPD	O
+3	O
+as	O
+compared	O
+with	O
+animals	O
+treated	O
+with	O
+CAPD	O
+3	O
+Balance	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+A	O
+further	O
+analysis	O
+has	O
+been	O
+performed	O
+using	O
+the	O
+series	O
+of	O
+maximum	O
+intensity	O
+for	O
+fixed	O
+duration	O
+(	O
+1	O
+,	O
+3	O
+,	O
+6	O
+,	O
+12	O
+,	O
+24	O
+hrs	O
+)	O
+and	O
+annual	O
+daily	O
+maxima	O
+.	O
+
+BACKGROUND	O
+:	O
+We	O
+hypothesized	O
+that	O
+the	O
+postoperative	O
+serum	O
+level	O
+of	O
+TA90	B-GENE
+-	I-GENE
+IC	I-GENE
+,	O
+an	O
+immune	O
+complex	O
+of	O
+a	O
+90	O
+-	O
+kDa	O
+tumor	O
+-	O
+associated	O
+antigen	O
+and	O
+its	O
+antibody	O
+,	O
+might	O
+have	O
+a	O
+significant	O
+correlation	O
+with	O
+recurrence	O
+and	O
+survival	O
+in	O
+patients	O
+with	O
+thick	O
+primary	O
+melanomas	O
+.	O
+
+Genetics	O
+Institute	O
+has	O
+developed	O
+and	O
+launched	O
+oprelvekin	B-GENE
+(	O
+rhIL	B-GENE
+-	I-GENE
+11	I-GENE
+;	O
+Neumega	O
+)	O
+,	O
+a	O
+recombinant	O
+form	O
+of	O
+human	B-GENE
+IL	I-GENE
+-	I-GENE
+11	I-GENE
+.	O
+
+Patients	O
+subsequently	O
+returned	O
+to	O
+the	O
+clinic	O
+every	O
+3	O
+days	O
+to	O
+have	O
+the	O
+wounds	O
+checked	O
+and	O
+dressings	O
+changed	O
+.	O
+
+Elements	O
+that	O
+are	O
+fundamental	O
+to	O
+the	O
+safety	O
+evaluation	O
+of	O
+flavor	O
+ingredients	O
+include	O
+exposure	O
+,	O
+structural	O
+analogy	O
+,	O
+metabolism	O
+,	O
+pharmacokinetics	O
+and	O
+toxicology	O
+.	O
+
+The	O
+mass	O
+-	O
+specific	O
+resting	O
+minute	O
+ventilation	O
+(	O
+E	O
+)	O
+and	O
+the	O
+ventilatory	O
+equivalent	O
+(	O
+VE	O
+/	O
+(	O
+O	O
+(	O
+2	O
+)	O
+)	O
+)	O
+were	O
+approximately	O
+the	O
+same	O
+at	O
+the	O
+two	O
+ages	O
+,	O
+with	O
+a	O
+breathing	O
+pattern	O
+significantly	O
+deeper	O
+and	O
+slower	O
+at	O
+day	O
+1	O
+.	O
+
+INTERPRETATION	O
+:	O
+It	O
+is	O
+probable	O
+that	O
+the	O
+cognitive	O
+dissonance	O
+created	O
+by	O
+more	O
+health	O
+information	O
+on	O
+smoking	O
+after	O
+1964	O
+,	O
+i	O
+.	O
+e	O
+.	O
+the	O
+necessary	O
+motivation	O
+to	O
+quit	O
+,	O
+was	O
+reduced	O
+as	O
+a	O
+result	O
+of	O
+strategic	O
+changes	O
+in	O
+the	O
+amount	O
+and	O
+content	O
+of	O
+advertising	O
+.	O
+
+Nine	O
+cases	O
+of	O
+GBS	O
+and	O
+five	O
+of	O
+TM	O
+reported	O
+to	O
+the	O
+active	O
+AFP	O
+surveillance	O
+were	O
+not	O
+found	O
+in	O
+the	O
+hospital	O
+searches	O
+.	O
+
+The	O
+ability	O
+of	O
+rats	O
+with	O
+control	O
+or	O
+hippocampal	O
+lesions	O
+to	O
+learn	O
+an	O
+object	O
+-	O
+place	O
+,	O
+odor	O
+-	O
+place	O
+,	O
+or	O
+object	O
+-	O
+odor	O
+paired	O
+-	O
+associate	O
+task	O
+was	O
+assessed	O
+in	O
+a	O
+cheeseboard	O
+maze	O
+apparatus	O
+.	O
+
+The	O
+shift	O
+in	O
+the	O
+earliest	O
+activation	O
+site	O
+after	O
+administration	O
+of	O
+esmolol	O
+was	O
+compared	O
+with	O
+the	O
+shift	O
+after	O
+RFA	O
+.	O
+RESULTS	O
+:	O
+The	O
+heart	O
+rate	O
+at	O
+rest	O
+and	O
+in	O
+drug	O
+-	O
+free	O
+state	O
+ranged	O
+between	O
+95	O
+and	O
+125	O
+beats	O
+/	O
+min	O
+(	O
+mean	O
+99	O
++	O
+/	O
+-	O
+14	O
+beats	O
+/	O
+min	O
+)	O
+.	O
+
+Urine	O
+samples	O
+collected	O
+after	O
+the	O
+administration	O
+of	O
+these	O
+supplements	O
+can	O
+test	O
+positive	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Lymphoscintigraphy	O
+of	O
+the	O
+cynomolgus	O
+monkey	O
+eyelids	O
+reveals	O
+discrete	O
+lymphatic	O
+drainage	O
+pathways	O
+for	O
+the	O
+upper	O
+and	O
+lower	O
+eyelids	O
+and	O
+a	O
+dual	O
+pathway	O
+for	O
+the	O
+central	O
+upper	O
+eyelid	O
+.	O
+
+Data	O
+management	O
+in	O
+practice	O
+-	O
+based	O
+research	O
+.	O
+
+We	O
+have	O
+previously	O
+reported	O
+reduced	O
+levels	O
+of	O
+choline	B-GENE
+acetyltransferase	I-GENE
+activity	O
+in	O
+the	O
+cerebral	O
+cortex	O
+of	O
+patients	O
+who	O
+died	O
+after	O
+a	O
+head	O
+injury	O
+,	O
+demonstrating	O
+that	O
+there	O
+is	O
+a	O
+loss	O
+of	O
+cortical	O
+cholinergic	O
+innervation	O
+.	O
+
+After	O
+taking	O
+smears	O
+from	O
+lesions	O
+of	O
+the	O
+oral	O
+mucosa	O
+(	O
+tongue	O
+,	O
+cheeks	O
+,	O
+palate	O
+)	O
+and	O
+the	O
+contiguous	O
+denture	O
+surface	O
+by	O
+cotton	O
+wool	O
+swabs	O
+and	O
+inoculating	O
+them	O
+onto	O
+Sabouraud	O
+glucose	O
+agar	O
+and	O
+CHROMagar	O
+Candida	O
+,	O
+individual	O
+yeast	O
+species	O
+were	O
+identified	O
+by	O
+a	O
+germ	O
+tube	O
+,	O
+filamentous	O
+,	O
+and	O
+assimilation	O
+tests	O
+employing	O
+the	O
+commercial	O
+kit	O
+AuxaColor	O
+.	O
+
+The	O
+effects	O
+of	O
+pharmacological	O
+treatment	O
+and	O
+professional	O
+care	O
+and	O
+support	O
+may	O
+improve	O
+when	O
+dementia	O
+is	O
+detected	O
+in	O
+an	O
+early	O
+stage	O
+.	O
+
+Sexually	O
+conditioned	O
+incentives	O
+:	O
+attenuation	O
+of	O
+motivational	O
+impact	O
+during	O
+dopamine	B-GENE
+receptor	I-GENE
+antagonism	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+This	O
+study	O
+is	O
+a	O
+retrospective	O
+cohort	O
+study	O
+of	O
+all	O
+children	O
+with	O
+cancer	O
+admitted	O
+to	O
+a	O
+single	O
+institution	O
+with	O
+fever	O
+and	O
+neutropenia	O
+(	O
+defined	O
+as	O
+an	O
+absolute	O
+neutrophil	O
+count	O
+<	O
+500	O
+cells	O
+/	O
+mm3	O
+)	O
+in	O
+a	O
+1	O
+-	O
+year	O
+period	O
+.	O
+
+Concentrations	O
+of	O
+N	O
+(	O
+O3	O
+-	O
+)	O
+-	O
+N	O
+and	O
+N	O
+(	O
+H3	O
+-	O
+)	O
+-	O
+N	O
+at	O
+Deoprayag	O
+varied	O
+from	O
+0	O
+.	O
+30	O
+to	O
+0	O
+.	O
+50	O
+and	O
+0	O
+.	O
+02	O
+to	O
+0	O
+.	O
+12	O
+mg	O
+/	O
+L	O
+,	O
+respectively	O
+,	O
+depending	O
+on	O
+season	O
+.	O
+
+Steal	O
+is	O
+a	O
+pathophysiological	O
+process	O
+in	O
+which	O
+increased	O
+blood	O
+flow	O
+through	O
+a	O
+low	O
+-	O
+resistance	O
+vascular	O
+bed	O
+is	O
+sufficient	O
+to	O
+divert	O
+flow	O
+away	O
+from	O
+a	O
+region	O
+of	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+The	O
+orientations	O
+of	O
+the	O
+contact	O
+surfaces	O
+and	O
+their	O
+locations	O
+relative	O
+to	O
+the	O
+object	O
+'	O
+s	O
+center	O
+of	O
+mass	O
+were	O
+varied	O
+.	O
+
+The	O
+results	O
+are	O
+given	O
+as	O
+:	O
+flux	O
+,	O
+number	O
+of	O
+stars	O
+per	O
+cm3	O
+,	O
+charge	O
+of	O
+the	O
+ions	O
+,	O
+comparison	O
+with	O
+other	O
+detectors	O
+(	O
+plastics	O
+,	O
+AgCl	O
+crystals	O
+,	O
+LiF	O
+)	O
+,	O
+energy	O
+loss	O
+,	O
+hit	O
+region	O
+in	O
+the	O
+biological	O
+objects	O
+.	O
+
+Nodal	O
+domains	O
+are	O
+regions	O
+where	O
+a	O
+function	O
+has	O
+definite	O
+sign	O
+.	O
+
+DESIGN	O
+:	O
+Prospective	O
+,	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+controlled	O
+trial	O
+.	O
+
+CONCLUSIONS	O
+:	O
+This	O
+retrospective	O
+uncontrolled	O
+study	O
+shows	O
+that	O
+in	O
+patients	O
+with	O
+type	O
+1	O
+HRS	O
+,	O
+terlipressin	O
+-	O
+induced	O
+improved	O
+renal	O
+function	O
+is	O
+associated	O
+with	O
+an	O
+increase	O
+in	O
+survival	O
+.	O
+
+Calcimimetic	O
+agents	O
+directly	O
+inhibit	O
+PTH	B-GENE
+secretion	O
+by	O
+activating	O
+the	O
+calcium	O
+-	O
+sensing	O
+receptor	O
+in	O
+the	O
+parathyroid	O
+glands	O
+,	O
+but	O
+clinical	O
+experience	O
+with	O
+them	O
+is	O
+limited	O
+.	O
+
+The	O
+subjects	O
+were	O
+shown	O
+to	O
+be	O
+capable	O
+of	O
+assessing	O
+integrally	O
+the	O
+value	O
+of	O
+accelerations	O
+and	O
+estimating	O
+it	O
+with	O
+an	O
+error	O
+of	O
+0	O
+.	O
+1	O
+-	O
+0	O
+.	O
+12	O
+g	O
+.	O
+
+The	O
+observed	O
+incidence	O
+rates	O
+were	O
+compared	O
+to	O
+expected	O
+rates	O
+in	O
+the	O
+general	O
+population	O
+.	O
+
+The	O
+only	O
+predictor	O
+of	O
+response	O
+to	O
+tacrolimus	O
+was	O
+a	O
+previous	O
+response	O
+to	O
+cyclosporin	O
+and	O
+prednisone	O
+,	O
+either	O
+as	O
+a	O
+complete	O
+or	O
+partial	O
+remission	O
+(	O
+remission	O
+rate	O
+75	O
+%	O
+vs	O
+15	O
+.	O
+3	O
+;	O
+P	O
+=	O
+0	O
+.	O
+036	O
+)	O
+.	O
+
+Based	O
+on	O
+a	O
+morphological	O
+study	O
+of	O
+the	O
+resin	O
+-	O
+dentine	O
+interface	O
+,	O
+a	O
+broad	O
+selection	O
+of	O
+dentine	O
+adhesive	O
+systems	O
+was	O
+classified	O
+following	O
+their	O
+adhesion	O
+-	O
+strategy	O
+.	O
+
+Copyright	O
+2002	O
+American	O
+Cancer	O
+Society	O
+.	O
+DOI	O
+10	O
+.	O
+1002	O
+/	O
+cncr	O
+.	O
+10318	O
+
+As	O
+measured	O
+by	O
+the	O
+PDQ	O
+-	O
+39	O
+,	O
+STN	O
+-	O
+DBS	O
+significantly	O
+improves	O
+important	O
+aspects	O
+of	O
+QoL	O
+in	O
+patients	O
+with	O
+advanced	O
+PD	O
+.	O
+
+Selegiline	B-Chemical
+-	O
+induced	O
+postural	B-Disease
+hypotension	I-Disease
+in	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+:	O
+a	O
+longitudinal	O
+study	O
+on	O
+the	O
+effects	O
+of	O
+drug	O
+withdrawal	O
+.	O
+
+OBJECTIVES	O
+:	O
+The	O
+United	O
+Kingdom	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+Disease	I-Disease
+Research	O
+Group	O
+(	O
+UKPDRG	O
+)	O
+trial	O
+found	O
+an	O
+increased	O
+mortality	O
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+randomized	O
+to	O
+receive	O
+10	O
+mg	O
+selegiline	B-Chemical
+per	O
+day	O
+and	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+compared	O
+with	O
+those	O
+taking	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+alone	O
+.	O
+
+Recently	O
+,	O
+we	O
+found	O
+that	O
+therapy	O
+with	O
+selegiline	B-Chemical
+and	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+was	O
+associated	O
+with	O
+selective	O
+systolic	B-Disease
+orthostatic	I-Disease
+hypotension	I-Disease
+which	O
+was	O
+abolished	O
+by	O
+withdrawal	O
+of	O
+selegiline	B-Chemical
+.	O
+
+This	O
+unwanted	O
+effect	O
+on	O
+postural	O
+blood	O
+pressure	O
+was	O
+not	O
+the	O
+result	O
+of	O
+underlying	O
+autonomic	O
+failure	O
+.	O
+
+The	O
+aims	O
+of	O
+this	O
+study	O
+were	O
+to	O
+confirm	O
+our	O
+previous	O
+findings	O
+in	O
+a	O
+separate	O
+cohort	O
+of	O
+patients	O
+and	O
+to	O
+determine	O
+the	O
+time	O
+course	O
+of	O
+the	O
+cardiovascular	O
+consequences	O
+of	O
+stopping	O
+selegiline	B-Chemical
+in	O
+the	O
+expectation	O
+that	O
+this	O
+might	O
+shed	O
+light	O
+on	O
+the	O
+mechanisms	O
+by	O
+which	O
+the	O
+drug	O
+causes	O
+orthostatic	B-Disease
+hypotension	I-Disease
+.	O
+
+METHODS	O
+:	O
+The	O
+cardiovascular	O
+responses	O
+to	O
+standing	O
+and	O
+head	O
+-	O
+up	O
+tilt	O
+were	O
+studied	O
+repeatedly	O
+in	O
+PD	B-Disease
+patients	O
+receiving	O
+selegiline	B-Chemical
+and	O
+as	O
+the	O
+drug	O
+was	O
+withdrawn	O
+.	O
+
+RESULTS	O
+:	O
+Head	O
+-	O
+up	O
+tilt	O
+caused	O
+systolic	B-Disease
+orthostatic	I-Disease
+hypotension	I-Disease
+which	O
+was	O
+marked	O
+in	O
+six	O
+of	O
+20	O
+PD	B-Disease
+patients	O
+on	O
+selegiline	B-Chemical
+,	O
+one	O
+of	O
+whom	O
+lost	O
+consciousness	O
+with	O
+unrecordable	O
+blood	O
+pressures	O
+.	O
+
+A	O
+lesser	O
+degree	O
+of	O
+orthostatic	B-Disease
+hypotension	I-Disease
+occurred	O
+with	O
+standing	O
+.	O
+
+Orthostatic	B-Disease
+hypotension	I-Disease
+was	O
+ameliorated	O
+4	O
+days	O
+after	O
+withdrawal	O
+of	O
+selegiline	B-Chemical
+and	O
+totally	O
+abolished	O
+7	O
+days	O
+after	O
+discontinuation	O
+of	O
+the	O
+drug	O
+.	O
+
+Stopping	O
+selegiline	B-Chemical
+also	O
+significantly	O
+reduced	B-Disease
+the	I-Disease
+supine	I-Disease
+systolic	I-Disease
+and	I-Disease
+diastolic	I-Disease
+blood	I-Disease
+pressures	I-Disease
+consistent	O
+with	O
+a	O
+previously	O
+undescribed	O
+supine	O
+pressor	O
+action	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+study	O
+confirms	O
+our	O
+previous	O
+finding	O
+that	O
+selegiline	B-Chemical
+in	O
+combination	O
+with	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+is	O
+associated	O
+with	O
+selective	O
+orthostatic	B-Disease
+hypotension	I-Disease
+.	O
+
+The	O
+possibilities	O
+that	O
+these	O
+cardiovascular	O
+findings	O
+might	O
+be	O
+the	O
+result	O
+of	O
+non	O
+-	O
+selective	O
+inhibition	O
+of	O
+monoamine	O
+oxidase	O
+or	O
+of	O
+amphetamine	B-Chemical
+and	O
+metamphetamine	B-Chemical
+are	O
+discussed	O
+.	O
+
+Further	O
+studies	O
+on	O
+effects	O
+of	O
+irrigation	O
+solutions	O
+on	O
+rat	O
+bladders	O
+.	O
+
+Further	O
+studies	O
+on	O
+the	O
+effects	O
+of	O
+certain	O
+irrigating	O
+fluids	O
+on	O
+the	O
+rat	O
+bladder	O
+for	O
+18	O
+hours	O
+are	O
+reported	O
+.	O
+
+The	O
+results	O
+have	O
+shown	O
+that	O
+the	O
+degradation	O
+product	O
+p	B-Chemical
+-	I-Chemical
+choloroaniline	I-Chemical
+is	O
+not	O
+a	O
+significant	O
+factor	O
+in	O
+chlorhexidine	B-Chemical
+-	I-Chemical
+digluconate	I-Chemical
+associated	O
+erosive	O
+cystitis	B-Disease
+.	O
+
+A	O
+high	O
+percentage	O
+of	O
+kanamycin	B-Chemical
+-	O
+colistin	B-Chemical
+and	O
+povidone	B-Chemical
+-	I-Chemical
+iodine	I-Chemical
+irrigations	O
+were	O
+associated	O
+with	O
+erosive	O
+cystitis	B-Disease
+and	O
+suggested	O
+a	O
+possible	O
+complication	O
+with	O
+human	O
+usage	O
+.	O
+
+Picloxydine	B-Chemical
+irrigations	O
+appeared	O
+to	O
+have	O
+a	O
+lower	O
+incidence	O
+of	O
+erosive	O
+cystitis	B-Disease
+but	O
+further	O
+studies	O
+would	O
+have	O
+to	O
+be	O
+performed	O
+before	O
+it	O
+could	O
+be	O
+recommended	O
+for	O
+use	O
+in	O
+urological	O
+procedures	O
+.	O
+
+Effects	O
+of	O
+tetrandrine	B-Chemical
+and	O
+fangchinoline	B-Chemical
+on	O
+experimental	O
+thrombosis	B-Disease
+in	O
+mice	O
+and	O
+human	O
+platelet	B-Disease
+aggregation	I-Disease
+.	O
+
+Tetrandrine	B-Chemical
+(	O
+TET	B-Chemical
+)	O
+and	O
+fangchinoline	B-Chemical
+(	O
+FAN	B-Chemical
+)	O
+are	O
+two	O
+naturally	O
+occurring	O
+analogues	O
+with	O
+a	O
+bisbenzylisoquinoline	B-Chemical
+structure	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+undertaken	O
+to	O
+investigate	O
+the	O
+effects	O
+of	O
+TET	B-Chemical
+and	O
+FAN	B-Chemical
+on	O
+the	O
+experimental	O
+thrombosis	B-Disease
+induced	O
+by	O
+collagen	O
+plus	O
+epinephrine	B-Chemical
+(	O
+EP	B-Chemical
+)	O
+in	O
+mice	O
+,	O
+and	O
+platelet	B-Disease
+aggregation	I-Disease
+and	O
+blood	B-Disease
+coagulation	I-Disease
+in	O
+vitro	O
+.	O
+
+In	O
+the	O
+in	O
+vivo	O
+study	O
+,	O
+the	O
+administration	O
+(	O
+50	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+of	O
+TET	B-Chemical
+and	O
+FAN	B-Chemical
+in	O
+mice	O
+showed	O
+the	O
+inhibition	O
+of	O
+thrombosis	B-Disease
+by	O
+55	O
+%	O
+and	O
+35	O
+%	O
+,	O
+respectively	O
+,	O
+while	O
+acetylsalicylic	B-Chemical
+acid	I-Chemical
+(	O
+ASA	B-Chemical
+,	O
+50	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+,	O
+a	O
+positive	O
+control	O
+,	O
+showed	O
+only	O
+30	O
+%	O
+inhibition	O
+.	O
+
+In	O
+the	O
+vitro	O
+human	O
+platelet	B-Disease
+aggregations	I-Disease
+induced	O
+by	O
+the	O
+agonists	O
+used	O
+in	O
+tests	O
+,	O
+TET	B-Chemical
+and	O
+FAN	B-Chemical
+showed	O
+the	O
+inhibitions	O
+dose	O
+dependently	O
+.	O
+
+In	O
+addition	O
+,	O
+neither	O
+TET	B-Chemical
+nor	O
+FAN	B-Chemical
+showed	O
+any	O
+anticoagulation	O
+activities	O
+in	O
+the	O
+measurement	O
+of	O
+the	O
+activated	O
+partial	O
+thromboplastin	O
+time	O
+(	O
+APTT	O
+)	O
+,	O
+prothrombin	O
+time	O
+(	O
+PT	O
+)	O
+and	O
+thrombin	O
+time	O
+(	O
+TT	O
+)	O
+using	O
+human	O
+-	O
+citrated	O
+plasma	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+antithrombosis	O
+of	O
+TET	B-Chemical
+and	O
+FAN	B-Chemical
+in	O
+mice	O
+may	O
+be	O
+mainly	O
+related	O
+to	O
+the	O
+antiplatelet	O
+aggregation	O
+activities	O
+.	O
+
+Angioedema	B-Disease
+due	O
+to	O
+ACE	B-Chemical
+inhibitors	I-Chemical
+:	O
+common	O
+and	O
+inadequately	O
+diagnosed	O
+.	O
+
+The	O
+estimated	O
+incidence	O
+of	O
+angioedema	B-Disease
+during	O
+angiotensin	B-Chemical
+-	I-Chemical
+converting	I-Chemical
+enzyme	I-Chemical
+(	I-Chemical
+ACE	I-Chemical
+)	I-Chemical
+inhibitor	I-Chemical
+treatment	O
+is	O
+between	O
+1	O
+and	O
+7	O
+per	O
+thousand	O
+patients	O
+.	O
+
+This	O
+potentially	O
+serious	O
+adverse	O
+effect	O
+is	O
+often	O
+preceded	O
+by	O
+minor	O
+manifestations	O
+that	O
+may	O
+serve	O
+as	O
+a	O
+warning	O
+.	O
+
+Cocaine	B-Chemical
+-	O
+induced	O
+mood	B-Disease
+disorder	I-Disease
+:	O
+prevalence	O
+rates	O
+and	O
+psychiatric	B-Disease
+symptoms	O
+in	O
+an	O
+outpatient	O
+cocaine	B-Chemical
+-	O
+dependent	O
+sample	O
+.	O
+
+This	O
+paper	O
+attempts	O
+to	O
+examine	O
+and	O
+compare	O
+prevalence	O
+rates	O
+and	O
+symptom	O
+patterns	O
+of	O
+DSM	O
+substance	O
+-	O
+induced	O
+and	O
+other	O
+mood	B-Disease
+disorders	I-Disease
+.	O
+
+243	O
+cocaine	B-Chemical
+-	O
+dependent	O
+outpatients	O
+with	O
+cocaine	B-Chemical
+-	O
+induced	O
+mood	B-Disease
+disorder	I-Disease
+(	O
+CIMD	B-Disease
+)	O
+,	O
+other	O
+mood	B-Disease
+disorders	I-Disease
+,	O
+or	O
+no	O
+mood	B-Disease
+disorder	I-Disease
+were	O
+compared	O
+on	O
+measures	O
+of	O
+psychiatric	B-Disease
+symptoms	O
+.	O
+
+The	O
+prevalence	O
+rate	O
+for	O
+CIMD	B-Disease
+was	O
+12	O
+%	O
+at	O
+baseline	O
+.	O
+
+Introduction	O
+of	O
+the	O
+DSM	O
+-	O
+IV	O
+diagnosis	O
+of	O
+CIMD	B-Disease
+did	O
+not	O
+substantially	O
+affect	O
+rates	O
+of	O
+the	O
+other	O
+depressive	B-Disease
+disorders	I-Disease
+.	O
+
+Patients	O
+with	O
+CIMD	B-Disease
+had	O
+symptom	O
+severity	O
+levels	O
+between	O
+those	O
+of	O
+patients	O
+with	O
+and	O
+without	O
+a	O
+mood	B-Disease
+disorder	I-Disease
+.	O
+
+These	O
+findings	O
+suggest	O
+some	O
+validity	O
+for	O
+the	O
+new	O
+DSM	O
+-	O
+IV	O
+diagnosis	O
+of	O
+CIMD	B-Disease
+,	O
+but	O
+also	O
+suggest	O
+that	O
+it	O
+requires	O
+further	O
+specification	O
+and	O
+replication	O
+.	O
+
+Effect	O
+of	O
+fucoidan	B-Chemical
+treatment	O
+on	O
+collagenase	O
+-	O
+induced	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+in	O
+rats	O
+.	O
+
+Inflammatory	O
+cells	O
+are	O
+postulated	O
+to	O
+mediate	O
+some	O
+of	O
+the	O
+brain	B-Disease
+damage	I-Disease
+following	O
+ischemic	B-Disease
+stroke	I-Disease
+.	O
+
+Intracerebral	B-Disease
+hemorrhage	I-Disease
+is	O
+associated	O
+with	O
+more	O
+inflammation	B-Disease
+than	O
+ischemic	B-Disease
+stroke	I-Disease
+.	O
+
+We	O
+tested	O
+the	O
+sulfated	O
+polysaccharide	O
+fucoidan	B-Chemical
+,	O
+which	O
+has	O
+been	O
+reported	O
+to	O
+reduce	O
+inflammatory	O
+brain	B-Disease
+damage	I-Disease
+,	O
+in	O
+a	O
+rat	O
+model	O
+of	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+induced	O
+by	O
+injection	O
+of	O
+bacterial	O
+collagenase	O
+into	O
+the	O
+caudate	O
+nucleus	O
+.	O
+
+Rats	O
+were	O
+treated	O
+with	O
+seven	O
+day	O
+intravenous	O
+infusion	O
+of	O
+fucoidan	B-Chemical
+(	O
+30	O
+micrograms	O
+h	O
+-	O
+1	O
+)	O
+or	O
+vehicle	O
+.	O
+
+The	O
+hematoma	B-Disease
+was	O
+assessed	O
+in	O
+vivo	O
+by	O
+magnetic	O
+resonance	O
+imaging	O
+.	O
+
+Motor	O
+behavior	O
+,	O
+passive	O
+avoidance	O
+,	O
+and	O
+skilled	O
+forelimb	O
+function	O
+were	O
+tested	O
+repeatedly	O
+for	O
+six	O
+weeks	O
+.	O
+
+Fucoidan	B-Chemical
+-	O
+treated	O
+rats	O
+exhibited	O
+evidence	O
+of	O
+impaired	B-Disease
+blood	I-Disease
+clotting	I-Disease
+and	O
+hemodilution	B-Disease
+,	O
+had	O
+larger	O
+hematomas	B-Disease
+,	O
+and	O
+tended	O
+to	O
+have	O
+less	O
+inflammation	B-Disease
+in	O
+the	O
+vicinity	O
+of	O
+the	O
+hematoma	B-Disease
+after	O
+three	O
+days	O
+.	O
+
+They	O
+showed	O
+significantly	O
+more	O
+rapid	O
+improvement	O
+of	O
+motor	O
+function	O
+in	O
+the	O
+first	O
+week	O
+following	O
+hemorrhage	B-Disease
+and	O
+better	O
+memory	O
+retention	O
+in	O
+the	O
+passive	O
+avoidance	O
+test	O
+.	O
+
+Acute	O
+white	B-Disease
+matter	I-Disease
+edema	I-Disease
+and	O
+eventual	O
+neuronal	B-Disease
+loss	I-Disease
+in	O
+the	O
+striatum	O
+adjacent	O
+to	O
+the	O
+hematoma	B-Disease
+did	O
+not	O
+differ	O
+between	O
+the	O
+two	O
+groups	O
+.	O
+
+Investigation	O
+of	O
+more	O
+specific	O
+anti	O
+-	O
+inflammatory	O
+agents	O
+and	O
+hemodiluting	O
+agents	O
+are	O
+warranted	O
+in	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+.	O
+
+Recurarization	O
+in	O
+the	O
+recovery	O
+room	O
+.	O
+
+A	O
+case	O
+of	O
+recurarization	O
+in	O
+the	O
+recovery	O
+room	O
+is	O
+reported	O
+.	O
+
+Accumulation	O
+of	O
+atracurium	B-Chemical
+in	O
+the	O
+intravenous	O
+line	O
+led	O
+to	O
+recurarization	O
+after	O
+flushing	O
+the	O
+line	O
+in	O
+the	O
+recovery	O
+room	O
+.	O
+
+A	O
+respiratory	B-Disease
+arrest	I-Disease
+with	O
+severe	O
+desaturation	B-Disease
+and	O
+bradycardia	B-Disease
+occurred	O
+.	O
+
+Circumstances	O
+leading	O
+to	O
+this	O
+event	O
+and	O
+the	O
+mechanisms	O
+enabling	O
+a	O
+neuromuscular	B-Disease
+blockade	I-Disease
+to	O
+occur	O
+,	O
+following	O
+the	O
+administration	O
+of	O
+a	O
+small	O
+dose	O
+of	O
+relaxant	O
+,	O
+are	O
+discussed	O
+.	O
+
+The	O
+haemodynamic	O
+effects	O
+of	O
+propofol	B-Chemical
+in	O
+combination	O
+with	O
+ephedrine	B-Chemical
+in	O
+elderly	O
+patients	O
+(	O
+ASA	O
+groups	O
+3	O
+and	O
+4	O
+)	O
+.	O
+
+The	O
+marked	O
+vasodilator	O
+and	O
+negative	O
+inotropic	O
+effects	O
+of	O
+propofol	B-Chemical
+are	O
+disadvantages	O
+in	O
+frail	O
+elderly	O
+patients	O
+.	O
+
+We	O
+investigated	O
+the	O
+safety	O
+and	O
+efficacy	O
+of	O
+adding	O
+different	O
+doses	O
+of	O
+ephedrine	B-Chemical
+to	O
+propofol	B-Chemical
+in	O
+order	O
+to	O
+obtund	O
+the	O
+hypotensive	B-Disease
+response	O
+.	O
+
+The	O
+haemodynamic	O
+effects	O
+of	O
+adding	O
+15	O
+,	O
+20	O
+or	O
+25	O
+mg	O
+of	O
+ephedrine	B-Chemical
+to	O
+200	O
+mg	O
+of	O
+propofol	B-Chemical
+were	O
+compared	O
+to	O
+control	O
+in	O
+40	O
+ASA	O
+3	O
+/	O
+4	O
+patients	O
+over	O
+60	O
+years	O
+presenting	O
+for	O
+genito	O
+-	O
+urinary	O
+surgery	O
+.	O
+
+The	O
+addition	O
+of	O
+ephedrine	B-Chemical
+to	O
+propofol	B-Chemical
+appears	O
+to	O
+be	O
+an	O
+effective	O
+method	O
+of	O
+obtunding	O
+the	O
+hypotensive	B-Disease
+response	O
+to	O
+propofol	B-Chemical
+at	O
+all	O
+doses	O
+used	O
+in	O
+this	O
+study	O
+.	O
+
+However	O
+,	O
+marked	O
+tachycardia	B-Disease
+associated	O
+with	O
+the	O
+use	O
+of	O
+ephedrine	B-Chemical
+in	O
+combination	O
+with	O
+propofol	B-Chemical
+occurred	O
+in	O
+the	O
+majority	O
+of	O
+patients	O
+,	O
+occasionally	O
+reaching	O
+high	O
+levels	O
+in	O
+individual	O
+patients	O
+.	O
+
+Due	O
+to	O
+the	O
+risk	O
+of	O
+this	O
+tachycardia	B-Disease
+inducing	O
+myocardial	B-Disease
+ischemia	I-Disease
+,	O
+we	O
+would	O
+not	O
+recommend	O
+the	O
+use	O
+in	O
+elderly	O
+patients	O
+of	O
+any	O
+of	O
+the	O
+ephedrine	B-Chemical
+/	O
+propofol	B-Chemical
+/	O
+mixtures	O
+studied	O
+.	O
+
+Gemcitabine	B-Chemical
+plus	O
+vinorelbine	B-Chemical
+in	O
+nonsmall	B-Disease
+cell	I-Disease
+lung	I-Disease
+carcinoma	I-Disease
+patients	O
+age	O
+70	O
+years	O
+or	O
+older	O
+or	O
+patients	O
+who	O
+cannot	O
+receive	O
+cisplatin	B-Chemical
+.	O
+
+Oncopaz	O
+Cooperative	O
+Group	O
+.	O
+
+BACKGROUND	O
+:	O
+Although	O
+the	O
+prevalence	O
+of	O
+nonsmall	B-Disease
+cell	I-Disease
+lung	I-Disease
+carcinoma	I-Disease
+(	O
+NSCLC	B-Disease
+)	O
+is	O
+high	O
+among	O
+elderly	O
+patients	O
+,	O
+few	O
+data	O
+are	O
+available	O
+regarding	O
+the	O
+efficacy	O
+and	O
+toxicity	B-Disease
+of	O
+chemotherapy	O
+in	O
+this	O
+group	O
+of	O
+patients	O
+.	O
+
+Recent	O
+reports	O
+indicate	O
+that	O
+single	O
+agent	O
+therapy	O
+with	O
+vinorelbine	B-Chemical
+(	O
+VNB	B-Chemical
+)	O
+or	O
+gemcitabine	B-Chemical
+(	O
+GEM	B-Chemical
+)	O
+may	O
+obtain	O
+a	O
+response	O
+rate	O
+of	O
+20	O
+-	O
+30	O
+%	O
+in	O
+elderly	O
+patients	O
+,	O
+with	O
+acceptable	O
+toxicity	B-Disease
+and	O
+improvement	O
+in	O
+symptoms	O
+and	O
+quality	O
+of	O
+life	O
+.	O
+
+In	O
+the	O
+current	O
+study	O
+the	O
+efficacy	O
+and	O
+toxicity	B-Disease
+of	O
+the	O
+combination	O
+of	O
+GEM	B-Chemical
+and	O
+VNB	B-Chemical
+in	O
+elderly	O
+patients	O
+with	O
+advanced	O
+NSCLC	B-Disease
+or	O
+those	O
+with	O
+some	O
+contraindication	O
+to	O
+receiving	O
+cisplatin	B-Chemical
+were	O
+assessed	O
+.	O
+
+METHODS	O
+:	O
+Forty	O
+-	O
+nine	O
+patients	O
+with	O
+advanced	O
+NSCLC	B-Disease
+were	O
+included	O
+,	O
+38	O
+of	O
+whom	O
+were	O
+age	O
+>	O
+/	O
+=	O
+70	O
+years	O
+and	O
+11	O
+were	O
+age	O
+<	O
+70	O
+years	O
+but	O
+who	O
+had	O
+some	O
+contraindication	O
+to	O
+receiving	O
+cisplatin	B-Chemical
+.	O
+
+All	O
+patients	O
+were	O
+evaluable	O
+for	O
+response	O
+and	O
+toxicity	B-Disease
+.	O
+
+Treatment	O
+was	O
+comprised	O
+of	O
+VNB	B-Chemical
+,	O
+25	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+,	O
+plus	O
+GEM	B-Chemical
+,	O
+1000	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+,	O
+both	O
+on	O
+Days	O
+1	O
+,	O
+8	O
+,	O
+and	O
+15	O
+every	O
+28	O
+days	O
+.	O
+
+Patients	O
+received	O
+a	O
+minimum	O
+of	O
+three	O
+courses	O
+unless	O
+progressive	O
+disease	O
+was	O
+detected	O
+.	O
+
+RESULTS	O
+:	O
+One	O
+hundred	O
+sixty	O
+-	O
+five	O
+courses	O
+were	O
+administered	O
+,	O
+with	O
+a	O
+median	O
+of	O
+3	O
+.	O
+
+6	O
+courses	O
+per	O
+patient	O
+.	O
+
+The	O
+overall	O
+response	O
+rate	O
+was	O
+26	O
+%	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+,	O
+15	O
+-	O
+41	O
+%	O
+)	O
+.	O
+
+Two	O
+patients	O
+attained	O
+a	O
+complete	O
+response	O
+(	O
+4	O
+%	O
+)	O
+and	O
+11	O
+patients	O
+(	O
+22	O
+%	O
+)	O
+achieved	O
+a	O
+partial	O
+response	O
+.	O
+
+Eastern	O
+Cooperative	O
+Oncology	O
+Group	O
+performance	O
+status	O
+improved	O
+in	O
+35	O
+%	O
+of	O
+those	O
+patients	O
+with	O
+an	O
+initial	O
+value	O
+>	O
+0	O
+,	O
+whereas	O
+relief	O
+of	O
+at	O
+least	O
+1	O
+symptom	O
+without	O
+worsening	O
+of	O
+other	O
+symptoms	O
+was	O
+noted	O
+in	O
+27	O
+patients	O
+(	O
+55	O
+%	O
+)	O
+.	O
+
+The	O
+median	O
+time	O
+to	O
+progression	O
+was	O
+16	O
+weeks	O
+and	O
+the	O
+1	O
+-	O
+year	O
+survival	O
+rate	O
+was	O
+33	O
+%	O
+.	O
+
+Toxicity	B-Disease
+was	O
+mild	O
+.	O
+
+Six	O
+patients	O
+(	O
+12	O
+%	O
+)	O
+had	O
+World	O
+Health	O
+Organization	O
+Grade	O
+3	O
+-	O
+4	O
+neutropenia	B-Disease
+,	O
+2	O
+patients	O
+(	O
+4	O
+%	O
+)	O
+had	O
+Grade	O
+3	O
+-	O
+4	O
+thrombocytopenia	B-Disease
+,	O
+and	O
+2	O
+patients	O
+(	O
+4	O
+%	O
+)	O
+had	O
+Grade	O
+3	O
+neurotoxicity	B-Disease
+.	O
+
+Three	O
+patients	O
+with	O
+severe	O
+neutropenia	B-Disease
+(	O
+6	O
+%	O
+)	O
+died	O
+of	O
+sepsis	B-Disease
+.	O
+
+The	O
+median	O
+age	O
+of	O
+those	O
+patients	O
+developing	O
+Grade	O
+3	O
+-	O
+4	O
+neutropenia	B-Disease
+was	O
+significantly	O
+higher	O
+than	O
+that	O
+of	O
+the	O
+remaining	O
+patients	O
+(	O
+75	O
+years	O
+vs	O
+.	O
+72	O
+years	O
+;	O
+P	O
+=	O
+0	O
+.	O
+047	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+combination	O
+of	O
+GEM	B-Chemical
+and	O
+VNB	B-Chemical
+is	O
+moderately	O
+active	O
+and	O
+well	O
+tolerated	O
+except	O
+in	O
+patients	O
+age	O
+>	O
+/	O
+=	O
+75	O
+years	O
+.	O
+
+This	O
+age	O
+group	O
+had	O
+an	O
+increased	O
+risk	O
+of	O
+myelosuppression	B-Disease
+.	O
+
+Therefore	O
+the	O
+prophylactic	O
+use	O
+of	O
+granulocyte	O
+-	O
+colony	O
+stimulating	O
+factor	O
+should	O
+be	O
+considered	O
+with	O
+this	O
+treatment	O
+.	O
+
+New	O
+chemotherapy	O
+combinations	O
+with	O
+higher	O
+activity	O
+and	O
+lower	O
+toxicity	B-Disease
+are	O
+needed	O
+for	O
+elderly	O
+patients	O
+with	O
+advanced	O
+NSCLC	B-Disease
+.	O
+
+A	O
+selective	O
+dopamine	B-Chemical
+D4	O
+receptor	O
+antagonist	O
+,	O
+NRA0160	B-Chemical
+:	O
+a	O
+preclinical	O
+neuropharmacological	O
+profile	O
+.	O
+
+NRA0160	B-Chemical
+,	O
+5	B-Chemical
+-	I-Chemical
+[	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+3	I-Chemical
+-	I-Chemical
+fluorobenzylidene	I-Chemical
+)	I-Chemical
+piperidin	I-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+yl	I-Chemical
+)	I-Chemical
+ethyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+4	I-Chemical
+-	I-Chemical
+fluorophenyl	I-Chemical
+)	I-Chemical
+thiazole	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+carboxamide	I-Chemical
+,	O
+has	O
+a	O
+high	O
+affinity	O
+for	O
+human	O
+cloned	O
+dopamine	B-Chemical
+D4	O
+.	O
+2	O
+,	O
+D4	O
+.	O
+4	O
+and	O
+D4	O
+.	O
+7	O
+receptors	O
+,	O
+with	O
+Ki	O
+values	O
+of	O
+0	O
+.	O
+5	O
+,	O
+0	O
+.	O
+9	O
+and	O
+2	O
+.	O
+7	O
+nM	O
+,	O
+respectively	O
+.	O
+
+NRA0160	B-Chemical
+is	O
+over	O
+20	O
+,	O
+000fold	O
+more	O
+potent	O
+at	O
+the	O
+dopamine	B-Chemical
+D4	O
+.	O
+2	O
+receptor	O
+compared	O
+with	O
+the	O
+human	O
+cloned	O
+dopamine	B-Chemical
+D2L	O
+receptor	O
+.	O
+
+NRA0160	B-Chemical
+has	O
+negligible	O
+affinity	O
+for	O
+the	O
+human	O
+cloned	O
+dopamine	B-Chemical
+D3	O
+receptor	O
+(	O
+Ki	O
+=	O
+39	O
+nM	O
+)	O
+,	O
+rat	O
+serotonin	B-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+)	O
+2A	O
+receptors	O
+(	O
+Ki	O
+=	O
+180	O
+nM	O
+)	O
+and	O
+rat	O
+alpha1	O
+adrenoceptor	O
+(	O
+Ki	O
+=	O
+237	O
+nM	O
+)	O
+.	O
+
+NRA0160	B-Chemical
+and	O
+clozapine	B-Chemical
+antagonized	O
+locomotor	O
+hyperactivity	B-Disease
+induced	O
+by	O
+methamphetamine	B-Chemical
+(	O
+MAP	B-Chemical
+)	O
+in	O
+mice	O
+.	O
+
+NRA0160	B-Chemical
+and	O
+clozapine	B-Chemical
+antagonized	O
+MAP	B-Chemical
+-	O
+induced	O
+stereotyped	O
+behavior	O
+in	O
+mice	O
+,	O
+although	O
+their	O
+effects	O
+did	O
+not	O
+exceed	O
+50	O
+%	O
+inhibition	O
+,	O
+even	O
+at	O
+the	O
+highest	O
+dose	O
+given	O
+.	O
+
+NRA0160	B-Chemical
+and	O
+clozapine	B-Chemical
+significantly	O
+induced	O
+catalepsy	B-Disease
+in	O
+rats	O
+,	O
+although	O
+their	O
+effects	O
+did	O
+not	O
+exceed	O
+50	O
+%	O
+induction	O
+even	O
+at	O
+the	O
+highest	O
+dose	O
+given	O
+.	O
+
+NRA0160	B-Chemical
+and	O
+clozapine	B-Chemical
+significantly	O
+reversed	O
+the	O
+disruption	O
+of	O
+prepulse	O
+inhibition	O
+(	O
+PPI	O
+)	O
+in	O
+rats	O
+produced	O
+by	O
+apomorphine	B-Chemical
+.	O
+
+NRA0160	B-Chemical
+and	O
+clozapine	B-Chemical
+significantly	O
+shortened	O
+the	O
+phencyclidine	B-Chemical
+(	O
+PCP	B-Chemical
+)	O
+-	O
+induced	O
+prolonged	O
+swimming	O
+latency	O
+in	O
+rats	O
+in	O
+a	O
+water	O
+maze	O
+task	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+NRA0160	B-Chemical
+may	O
+have	O
+unique	O
+antipsychotic	O
+activities	O
+without	O
+the	O
+liability	O
+of	O
+motor	O
+side	O
+effects	O
+typical	O
+of	O
+classical	O
+antipsychotics	O
+.	O
+
+Warfarin	B-Chemical
+-	O
+induced	O
+artery	B-Disease
+calcification	I-Disease
+is	O
+accelerated	O
+by	O
+growth	O
+and	O
+vitamin	B-Chemical
+D	I-Chemical
+.	O
+
+The	O
+present	O
+studies	O
+demonstrate	O
+that	O
+growth	O
+and	O
+vitamin	B-Chemical
+D	I-Chemical
+treatment	O
+enhance	O
+the	O
+extent	O
+of	O
+artery	B-Disease
+calcification	I-Disease
+in	O
+rats	O
+given	O
+sufficient	O
+doses	O
+of	O
+Warfarin	B-Chemical
+to	O
+inhibit	O
+gamma	O
+-	O
+carboxylation	O
+of	O
+matrix	O
+Gla	O
+protein	O
+,	O
+a	O
+calcification	B-Disease
+inhibitor	O
+known	O
+to	O
+be	O
+expressed	O
+by	O
+smooth	O
+muscle	O
+cells	O
+and	O
+macrophages	O
+in	O
+the	O
+artery	O
+wall	O
+.	O
+
+The	O
+first	O
+series	O
+of	O
+experiments	O
+examined	O
+the	O
+influence	O
+of	O
+age	O
+and	O
+growth	O
+status	O
+on	O
+artery	B-Disease
+calcification	I-Disease
+in	O
+Warfarin	B-Chemical
+-	O
+treated	O
+rats	O
+.	O
+
+Treatment	O
+for	O
+2	O
+weeks	O
+with	O
+Warfarin	B-Chemical
+caused	O
+massive	O
+focal	O
+calcification	B-Disease
+of	I-Disease
+the	I-Disease
+artery	I-Disease
+media	O
+in	O
+20	O
+-	O
+day	O
+-	O
+old	O
+rats	O
+and	O
+less	O
+extensive	O
+focal	O
+calcification	B-Disease
+in	O
+42	O
+-	O
+day	O
+-	O
+old	O
+rats	O
+.	O
+
+In	O
+contrast	O
+,	O
+no	O
+artery	B-Disease
+calcification	I-Disease
+could	O
+be	O
+detected	O
+in	O
+10	O
+-	O
+month	O
+-	O
+old	O
+adult	O
+rats	O
+even	O
+after	O
+4	O
+weeks	O
+of	O
+Warfarin	B-Chemical
+treatment	O
+.	O
+
+To	O
+directly	O
+examine	O
+the	O
+importance	O
+of	O
+growth	O
+to	O
+Warfarin	B-Chemical
+-	O
+induced	O
+artery	B-Disease
+calcification	I-Disease
+in	O
+animals	O
+of	O
+the	O
+same	O
+age	O
+,	O
+20	O
+-	O
+day	O
+-	O
+old	O
+rats	O
+were	O
+fed	O
+for	O
+2	O
+weeks	O
+either	O
+an	O
+ad	O
+libitum	O
+diet	O
+or	O
+a	O
+6	O
+-	O
+g	O
+/	O
+d	O
+restricted	O
+diet	O
+that	O
+maintains	O
+weight	O
+but	O
+prevents	O
+growth	O
+.	O
+
+Concurrent	O
+treatment	O
+of	O
+both	O
+dietary	O
+groups	O
+with	O
+Warfarin	B-Chemical
+produced	O
+massive	O
+focal	O
+calcification	B-Disease
+of	I-Disease
+the	I-Disease
+artery	I-Disease
+media	O
+in	O
+the	O
+ad	O
+libitum	O
+-	O
+fed	O
+rats	O
+but	O
+no	O
+detectable	O
+artery	B-Disease
+calcification	I-Disease
+in	O
+the	O
+restricted	O
+-	O
+diet	O
+,	O
+growth	O
+-	O
+inhibited	O
+group	O
+.	O
+
+Although	O
+the	O
+explanation	O
+for	O
+the	O
+association	O
+between	O
+artery	B-Disease
+calcification	I-Disease
+and	O
+growth	O
+status	O
+cannot	O
+be	O
+determined	O
+from	O
+the	O
+present	O
+study	O
+,	O
+there	O
+was	O
+a	O
+relationship	O
+between	O
+higher	O
+serum	O
+phosphate	B-Chemical
+and	O
+susceptibility	O
+to	O
+artery	B-Disease
+calcification	I-Disease
+,	O
+with	O
+30	O
+%	O
+higher	O
+levels	O
+of	O
+serum	O
+phosphate	B-Chemical
+in	O
+young	O
+,	O
+ad	O
+libitum	O
+-	O
+fed	O
+rats	O
+compared	O
+with	O
+either	O
+of	O
+the	O
+groups	O
+that	O
+was	O
+resistant	O
+to	O
+Warfarin	B-Chemical
+-	O
+induced	O
+artery	B-Disease
+calcification	I-Disease
+,	O
+ie	O
+,	O
+the	O
+10	O
+-	O
+month	O
+-	O
+old	O
+rats	O
+and	O
+the	O
+restricted	O
+-	O
+diet	O
+,	O
+growth	O
+-	O
+inhibited	O
+young	O
+rats	O
+.	O
+
+This	O
+observation	O
+suggests	O
+that	O
+increased	O
+susceptibility	O
+to	O
+Warfarin	B-Chemical
+-	O
+induced	O
+artery	B-Disease
+calcification	I-Disease
+could	O
+be	O
+related	O
+to	O
+higher	O
+serum	O
+phosphate	B-Chemical
+levels	O
+.	O
+
+The	O
+second	O
+set	O
+of	O
+experiments	O
+examined	O
+the	O
+possible	O
+synergy	O
+between	O
+vitamin	B-Chemical
+D	I-Chemical
+and	O
+Warfarin	B-Chemical
+in	O
+artery	B-Disease
+calcification	I-Disease
+.	O
+
+High	O
+doses	O
+of	O
+vitamin	B-Chemical
+D	I-Chemical
+are	O
+known	O
+to	O
+cause	O
+calcification	B-Disease
+of	I-Disease
+the	I-Disease
+artery	I-Disease
+media	O
+in	O
+as	O
+little	O
+as	O
+3	O
+to	O
+4	O
+days	O
+.	O
+
+High	O
+doses	O
+of	O
+the	O
+vitamin	B-Chemical
+K	I-Chemical
+antagonist	O
+Warfarin	B-Chemical
+are	O
+also	O
+known	O
+to	O
+cause	O
+calcification	B-Disease
+of	I-Disease
+the	I-Disease
+artery	I-Disease
+media	O
+,	O
+but	O
+at	O
+treatment	O
+times	O
+of	O
+2	O
+weeks	O
+or	O
+longer	O
+yet	O
+not	O
+at	O
+1	O
+week	O
+.	O
+
+In	O
+the	O
+current	O
+study	O
+,	O
+we	O
+investigated	O
+the	O
+synergy	O
+between	O
+these	O
+2	O
+treatments	O
+and	O
+found	O
+that	O
+concurrent	O
+Warfarin	B-Chemical
+administration	O
+dramatically	O
+increased	O
+the	O
+extent	O
+of	O
+calcification	B-Disease
+in	O
+the	O
+media	O
+of	O
+vitamin	B-Chemical
+D	I-Chemical
+-	O
+treated	O
+rats	O
+at	O
+3	O
+and	O
+4	O
+days	O
+.	O
+
+There	O
+was	O
+a	O
+close	O
+parallel	O
+between	O
+the	O
+effect	O
+of	O
+vitamin	B-Chemical
+D	I-Chemical
+dose	O
+on	O
+artery	B-Disease
+calcification	I-Disease
+and	O
+the	O
+effect	O
+of	O
+vitamin	B-Chemical
+D	I-Chemical
+dose	O
+on	O
+the	O
+elevation	O
+of	O
+serum	O
+calcium	B-Chemical
+,	O
+which	O
+suggests	O
+that	O
+vitamin	B-Chemical
+D	I-Chemical
+may	O
+induce	O
+artery	B-Disease
+calcification	I-Disease
+through	O
+its	O
+effect	O
+on	O
+serum	O
+calcium	B-Chemical
+.	O
+
+Because	O
+Warfarin	B-Chemical
+treatment	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+elevation	O
+in	O
+serum	O
+calcium	B-Chemical
+produced	O
+by	O
+vitamin	B-Chemical
+D	I-Chemical
+,	O
+the	O
+synergy	O
+between	O
+Warfarin	B-Chemical
+and	O
+vitamin	B-Chemical
+D	I-Chemical
+is	O
+probably	O
+best	O
+explained	O
+by	O
+the	O
+hypothesis	O
+that	O
+Warfarin	B-Chemical
+inhibits	O
+the	O
+activity	O
+of	O
+matrix	O
+Gla	O
+protein	O
+as	O
+a	O
+calcification	B-Disease
+inhibitor	O
+.	O
+
+High	O
+levels	O
+of	O
+matrix	O
+Gla	O
+protein	O
+are	O
+found	O
+at	O
+sites	O
+of	O
+artery	B-Disease
+calcification	I-Disease
+in	O
+rats	O
+treated	O
+with	O
+vitamin	B-Chemical
+D	I-Chemical
+plus	O
+Warfarin	B-Chemical
+,	O
+and	O
+chemical	O
+analysis	O
+showed	O
+that	O
+the	O
+protein	O
+that	O
+accumulated	O
+was	O
+indeed	O
+not	O
+gamma	B-Chemical
+-	I-Chemical
+carboxylated	I-Chemical
+.	O
+
+These	O
+observations	O
+indicate	O
+that	O
+although	O
+the	O
+gamma	B-Chemical
+-	I-Chemical
+carboxyglutamate	I-Chemical
+residues	O
+of	O
+matrix	O
+Gla	O
+protein	O
+are	O
+apparently	O
+required	O
+for	O
+its	O
+function	O
+as	O
+a	O
+calcification	B-Disease
+inhibitor	O
+,	O
+they	O
+are	O
+not	O
+required	O
+for	O
+its	O
+accumulation	O
+at	O
+calcification	B-Disease
+sites	O
+.	O
+
+Test	O
+conditions	O
+influence	O
+the	O
+response	O
+to	O
+a	O
+drug	O
+challenge	O
+in	O
+rodents	O
+.	O
+
+These	O
+studies	O
+were	O
+conducted	O
+to	O
+examine	O
+the	O
+differential	O
+response	O
+to	O
+a	O
+drug	O
+challenge	O
+under	O
+varied	O
+experimental	O
+test	O
+conditions	O
+routinely	O
+employed	O
+to	O
+study	O
+drug	O
+-	O
+induced	O
+behavioral	O
+and	O
+neurophysiological	O
+responses	O
+in	O
+rodents	O
+.	O
+
+Apomorphine	B-Chemical
+,	O
+a	O
+nonselective	O
+dopamine	B-Chemical
+agonist	I-Chemical
+,	O
+was	O
+selected	O
+due	O
+to	O
+its	O
+biphasic	O
+behavioral	O
+effects	O
+,	O
+its	O
+ability	O
+to	O
+induce	O
+hypothermia	B-Disease
+,	O
+and	O
+to	O
+produce	O
+distinct	O
+changes	O
+to	O
+dopamine	B-Chemical
+turnover	O
+in	O
+the	O
+rodent	O
+brain	O
+.	O
+
+From	O
+such	O
+experiments	O
+there	O
+is	O
+evidence	O
+that	O
+characterization	O
+and	O
+detection	O
+of	O
+apomorphine	B-Chemical
+-	O
+induced	O
+activity	O
+in	O
+rodents	O
+critically	O
+depends	O
+upon	O
+the	O
+test	O
+conditions	O
+employed	O
+.	O
+
+In	O
+rats	O
+,	O
+detection	O
+of	O
+apomorphine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+was	O
+facilitated	O
+by	O
+a	O
+period	O
+of	O
+acclimatization	O
+to	O
+the	O
+test	O
+conditions	O
+.	O
+
+Moreover	O
+,	O
+test	O
+conditions	O
+can	O
+impact	O
+upon	O
+other	O
+physiological	O
+responses	O
+to	O
+apomorphine	B-Chemical
+such	O
+as	O
+drug	O
+-	O
+induced	O
+hypothermia	B-Disease
+.	O
+
+In	O
+mice	O
+,	O
+apomorphine	B-Chemical
+produced	O
+qualitatively	O
+different	O
+responses	O
+under	O
+novel	O
+conditions	O
+when	O
+compared	O
+to	O
+those	O
+behaviors	O
+elicited	O
+in	O
+the	O
+home	O
+test	O
+cage	O
+.	O
+
+Drug	O
+-	O
+induced	O
+gross	O
+activity	O
+counts	O
+were	O
+increased	O
+in	O
+the	O
+novel	O
+exploratory	O
+box	O
+only	O
+,	O
+while	O
+measures	O
+of	O
+stereotypic	O
+behavior	O
+were	O
+similar	O
+in	O
+both	O
+.	O
+
+By	O
+contrast	O
+,	O
+apomorphine	B-Chemical
+-	O
+induced	O
+locomotion	O
+was	O
+more	O
+prominent	O
+in	O
+the	O
+novel	O
+exploratory	O
+box	O
+.	O
+
+Dopamine	B-Chemical
+turnover	O
+ratios	O
+(	O
+DOPAC	B-Chemical
+:	O
+DA	B-Chemical
+and	O
+HVA	B-Chemical
+:	O
+DA	B-Chemical
+)	O
+were	O
+found	O
+to	O
+be	O
+lower	O
+in	O
+those	O
+animals	O
+exposed	O
+to	O
+the	O
+exploratory	O
+box	O
+when	O
+compared	O
+to	O
+their	O
+home	O
+cage	O
+counterparts	O
+.	O
+
+However	O
+,	O
+apomorphine	B-Chemical
+-	O
+induced	O
+reductions	O
+in	O
+striatal	O
+dopamine	B-Chemical
+turnover	O
+were	O
+detected	O
+in	O
+both	O
+novel	O
+and	O
+home	O
+cage	O
+environments	O
+.	O
+
+The	O
+implications	O
+of	O
+these	O
+findings	O
+are	O
+discussed	O
+with	O
+particular	O
+emphasis	O
+upon	O
+conducting	O
+psychopharmacological	O
+challenge	O
+tests	O
+in	O
+rodents	O
+.	O
+
+Hemolysis	B-Disease
+of	O
+human	O
+erythrocytes	O
+induced	O
+by	O
+tamoxifen	B-Chemical
+is	O
+related	O
+to	O
+disruption	O
+of	O
+membrane	O
+structure	O
+.	O
+
+Tamoxifen	B-Chemical
+(	O
+TAM	B-Chemical
+)	O
+,	O
+the	O
+antiestrogenic	O
+drug	O
+most	O
+widely	O
+prescribed	O
+in	O
+the	O
+chemotherapy	O
+of	O
+breast	B-Disease
+cancer	I-Disease
+,	O
+induces	O
+changes	O
+in	O
+normal	O
+discoid	O
+shape	O
+of	O
+erythrocytes	O
+and	O
+hemolytic	B-Disease
+anemia	I-Disease
+.	O
+
+This	O
+work	O
+evaluates	O
+the	O
+effects	O
+of	O
+TAM	B-Chemical
+on	O
+isolated	O
+human	O
+erythrocytes	O
+,	O
+attempting	O
+to	O
+identify	O
+the	O
+underlying	O
+mechanisms	O
+on	O
+TAM	B-Chemical
+-	O
+induced	O
+hemolytic	B-Disease
+anemia	I-Disease
+and	O
+the	O
+involvement	O
+of	O
+biomembranes	O
+in	O
+its	O
+cytostatic	O
+action	O
+mechanisms	O
+.	O
+
+TAM	B-Chemical
+induces	O
+hemolysis	B-Disease
+of	O
+erythrocytes	O
+as	O
+a	O
+function	O
+of	O
+concentration	O
+.	O
+
+The	O
+extension	O
+of	O
+hemolysis	B-Disease
+is	O
+variable	O
+with	O
+erythrocyte	O
+samples	O
+,	O
+but	O
+12	O
+.	O
+5	O
+microM	O
+TAM	B-Chemical
+induces	O
+total	O
+hemolysis	B-Disease
+of	O
+all	O
+tested	O
+suspensions	O
+.	O
+
+Despite	O
+inducing	O
+extensive	O
+erythrocyte	O
+lysis	O
+,	O
+TAM	B-Chemical
+does	O
+not	O
+shift	O
+the	O
+osmotic	O
+fragility	O
+curves	O
+of	O
+erythrocytes	O
+.	O
+
+The	O
+hemolytic	B-Disease
+effect	O
+of	O
+TAM	B-Chemical
+is	O
+prevented	O
+by	O
+low	O
+concentrations	O
+of	O
+alpha	B-Chemical
+-	I-Chemical
+tocopherol	I-Chemical
+(	O
+alpha	B-Chemical
+-	I-Chemical
+T	I-Chemical
+)	O
+and	O
+alpha	B-Chemical
+-	I-Chemical
+tocopherol	I-Chemical
+acetate	I-Chemical
+(	O
+alpha	B-Chemical
+-	I-Chemical
+TAc	I-Chemical
+)	O
+(	O
+inactivated	O
+functional	O
+hydroxyl	B-Chemical
+)	O
+indicating	O
+that	O
+TAM	B-Chemical
+-	O
+induced	O
+hemolysis	B-Disease
+is	O
+not	O
+related	O
+to	O
+oxidative	O
+membrane	O
+damage	O
+.	O
+
+This	O
+was	O
+further	O
+evidenced	O
+by	O
+absence	O
+of	O
+oxygen	B-Chemical
+consumption	O
+and	O
+hemoglobin	O
+oxidation	O
+both	O
+determined	O
+in	O
+parallel	O
+with	O
+TAM	B-Chemical
+-	O
+induced	O
+hemolysis	B-Disease
+.	O
+
+Furthermore	O
+,	O
+it	O
+was	O
+observed	O
+that	O
+TAM	B-Chemical
+inhibits	O
+the	O
+peroxidation	O
+of	O
+human	O
+erythrocytes	O
+induced	O
+by	O
+AAPH	B-Chemical
+,	O
+thus	O
+ruling	O
+out	O
+TAM	B-Chemical
+-	O
+induced	O
+cell	O
+oxidative	O
+stress	O
+.	O
+
+Hemolysis	B-Disease
+caused	O
+by	O
+TAM	B-Chemical
+was	O
+not	O
+preceded	O
+by	O
+the	O
+leakage	O
+of	O
+K	B-Chemical
+(	O
++	O
+)	O
+from	O
+the	O
+cells	O
+,	O
+also	O
+excluding	O
+a	O
+colloid	O
+-	O
+osmotic	O
+type	O
+mechanism	O
+of	O
+hemolysis	B-Disease
+,	O
+according	O
+to	O
+the	O
+effects	O
+on	O
+osmotic	O
+fragility	O
+curves	O
+.	O
+
+However	O
+,	O
+TAM	B-Chemical
+induces	O
+release	O
+of	O
+peripheral	O
+proteins	O
+of	O
+membrane	O
+-	O
+cytoskeleton	O
+and	O
+cytosol	O
+proteins	O
+essentially	O
+bound	O
+to	O
+band	O
+3	O
+.	O
+
+Either	O
+alpha	B-Chemical
+-	I-Chemical
+T	I-Chemical
+or	O
+alpha	B-Chemical
+-	I-Chemical
+TAc	I-Chemical
+increases	O
+membrane	O
+packing	O
+and	O
+prevents	O
+TAM	B-Chemical
+partition	O
+into	O
+model	O
+membranes	O
+.	O
+
+These	O
+effects	O
+suggest	O
+that	O
+the	O
+protection	O
+from	O
+hemolysis	B-Disease
+by	O
+tocopherols	B-Chemical
+is	O
+related	O
+to	O
+a	O
+decreased	O
+TAM	B-Chemical
+incorporation	O
+in	O
+condensed	O
+membranes	O
+and	O
+the	O
+structural	O
+damage	O
+of	O
+the	O
+erythrocyte	O
+membrane	O
+is	O
+consequently	O
+avoided	O
+.	O
+
+Therefore	O
+,	O
+TAM	B-Chemical
+-	O
+induced	O
+hemolysis	B-Disease
+results	O
+from	O
+a	O
+structural	O
+perturbation	O
+of	O
+red	O
+cell	O
+membrane	O
+,	O
+leading	O
+to	O
+changes	O
+in	O
+the	O
+framework	O
+of	O
+the	O
+erythrocyte	O
+membrane	O
+and	O
+its	O
+cytoskeleton	O
+caused	O
+by	O
+its	O
+high	O
+partition	O
+in	O
+the	O
+membrane	O
+.	O
+
+These	O
+defects	O
+explain	O
+the	O
+abnormal	O
+erythrocyte	O
+shape	O
+and	O
+decreased	O
+mechanical	O
+stability	O
+promoted	O
+by	O
+TAM	B-Chemical
+,	O
+resulting	O
+in	O
+hemolytic	B-Disease
+anemia	I-Disease
+.	O
+
+Additionally	O
+,	O
+since	O
+membrane	O
+leakage	O
+is	O
+a	O
+final	O
+stage	O
+of	O
+cytotoxicity	O
+,	O
+the	O
+disruption	O
+of	O
+the	O
+structural	O
+characteristics	O
+of	O
+biomembranes	O
+by	O
+TAM	B-Chemical
+may	O
+contribute	O
+to	O
+the	O
+multiple	O
+mechanisms	O
+of	O
+its	O
+anticancer	O
+action	O
+.	O
+
+Changes	O
+of	O
+sodium	B-Chemical
+and	O
+ATP	B-Chemical
+affinities	O
+of	O
+the	O
+cardiac	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+during	O
+and	O
+after	O
+nitric	B-Chemical
+oxide	I-Chemical
+deficient	O
+hypertension	B-Disease
+.	O
+
+In	O
+the	O
+cardiovascular	O
+system	O
+,	O
+NO	B-Chemical
+is	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+a	O
+variety	O
+of	O
+functions	O
+.	O
+
+Inhibition	O
+of	O
+NO	B-Chemical
+synthesis	O
+induces	O
+sustained	O
+hypertension	B-Disease
+.	O
+
+In	O
+several	O
+models	O
+of	O
+hypertension	B-Disease
+,	O
+elevation	O
+of	O
+intracellular	O
+sodium	B-Chemical
+level	O
+was	O
+documented	O
+in	O
+cardiac	O
+tissue	O
+.	O
+
+To	O
+assess	O
+the	O
+molecular	O
+basis	O
+of	O
+disturbances	O
+in	O
+transmembraneous	O
+transport	O
+of	O
+Na	B-Chemical
++	O
+,	O
+we	O
+studied	O
+the	O
+response	O
+of	O
+cardiac	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+to	O
+NO	B-Chemical
+-	O
+deficient	O
+hypertension	B-Disease
+induced	O
+in	O
+rats	O
+by	O
+NO	B-Chemical
+-	O
+synthase	O
+inhibition	O
+with	O
+40	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+N	B-Chemical
+(	I-Chemical
+G	I-Chemical
+)	I-Chemical
+-	I-Chemical
+nitro	I-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+methyl	I-Chemical
+ester	I-Chemical
+(	O
+L	B-Chemical
+-	I-Chemical
+NAME	I-Chemical
+)	O
+for	O
+4	O
+four	O
+weeks	O
+.	O
+
+After	O
+4	O
+-	O
+week	O
+administration	O
+of	O
+L	B-Chemical
+-	I-Chemical
+NAME	I-Chemical
+,	O
+the	O
+systolic	O
+blood	O
+pressure	O
+(	O
+SBP	O
+)	O
+increased	O
+by	O
+36	O
+%	O
+.	O
+
+Two	O
+weeks	O
+after	O
+terminating	O
+the	O
+treatment	O
+,	O
+the	O
+SBP	O
+recovered	O
+to	O
+control	O
+value	O
+.	O
+
+When	O
+activating	O
+the	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+with	O
+its	O
+substrate	O
+ATP	B-Chemical
+,	O
+no	O
+changes	O
+in	O
+Km	O
+and	O
+Vmax	O
+values	O
+were	O
+observed	O
+in	O
+NO	B-Chemical
+-	O
+deficient	O
+rats	O
+.	O
+
+During	O
+activation	O
+with	O
+Na	B-Chemical
++	O
+,	O
+the	O
+Vmax	O
+remained	O
+unchanged	O
+,	O
+however	O
+the	O
+K	B-Chemical
+(	O
+Na	B-Chemical
+)	O
+increased	O
+by	O
+50	O
+%	O
+,	O
+indicating	O
+a	O
+profound	O
+decrease	O
+in	O
+the	O
+affinity	O
+of	O
+the	O
+Na	B-Chemical
++	O
+-	O
+binding	O
+site	O
+in	O
+NO	B-Chemical
+-	O
+deficient	O
+rats	O
+.	O
+
+After	O
+recovery	O
+from	O
+hypertension	B-Disease
+,	O
+the	O
+activity	O
+of	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+increased	O
+,	O
+due	O
+to	O
+higher	O
+affinity	O
+of	O
+the	O
+ATP	B-Chemical
+-	O
+binding	O
+site	O
+,	O
+as	O
+revealed	O
+from	O
+the	O
+lowered	O
+Km	O
+value	O
+for	O
+ATP	B-Chemical
+.	O
+
+The	O
+K	B-Chemical
+(	O
+Na	B-Chemical
+)	O
+value	O
+for	O
+Na	B-Chemical
++	O
+returned	O
+to	O
+control	O
+value	O
+.	O
+
+Inhibition	O
+of	O
+NO	B-Chemical
+-	O
+synthase	O
+induced	O
+a	O
+reversible	O
+hypertension	B-Disease
+accompanied	O
+by	O
+depressed	B-Disease
+Na	B-Chemical
++	O
+-	O
+extrusion	O
+from	O
+cardiac	O
+cells	O
+as	O
+a	O
+consequence	O
+of	O
+deteriorated	O
+Na	B-Chemical
++	O
+-	O
+binding	O
+properties	O
+of	O
+the	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+.	O
+
+After	O
+recovery	O
+of	O
+blood	O
+pressure	O
+to	O
+control	O
+values	O
+,	O
+the	O
+extrusion	O
+of	O
+Na	B-Chemical
++	O
+from	O
+cardiac	O
+cells	O
+was	O
+normalized	O
+,	O
+as	O
+revealed	O
+by	O
+restoration	O
+of	O
+the	O
+(	O
+Na	B-Chemical
+,	O
+K	B-Chemical
+)	O
+-	O
+ATPase	O
+activity	O
+.	O
+
+Effects	O
+of	O
+long	O
+-	O
+term	O
+pretreatment	O
+with	O
+isoproterenol	B-Chemical
+on	O
+bromocriptine	B-Chemical
+-	O
+induced	O
+tachycardia	B-Disease
+in	O
+conscious	O
+rats	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+that	O
+bromocriptine	B-Chemical
+-	O
+induced	O
+tachycardia	B-Disease
+,	O
+which	O
+persisted	O
+after	O
+adrenalectomy	O
+,	O
+is	O
+(	O
+i	O
+)	O
+mediated	O
+by	O
+central	O
+dopamine	B-Chemical
+D2	O
+receptor	O
+activation	O
+and	O
+(	O
+ii	O
+)	O
+reduced	O
+by	O
+5	O
+-	O
+day	O
+isoproterenol	B-Chemical
+pretreatment	O
+,	O
+supporting	O
+therefore	O
+the	O
+hypothesis	O
+that	O
+this	O
+effect	O
+is	O
+dependent	O
+on	O
+sympathetic	O
+outflow	O
+to	O
+the	O
+heart	O
+.	O
+
+This	O
+study	O
+was	O
+conducted	O
+to	O
+examine	O
+whether	O
+prolonged	O
+pretreatment	O
+with	O
+isoproterenol	B-Chemical
+could	O
+abolish	O
+bromocriptine	B-Chemical
+-	O
+induced	O
+tachycardia	B-Disease
+in	O
+conscious	O
+rats	O
+.	O
+
+Isoproterenol	B-Chemical
+pretreatment	O
+for	O
+15	O
+days	O
+caused	O
+cardiac	B-Disease
+hypertrophy	I-Disease
+without	O
+affecting	O
+baseline	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+.	O
+
+In	O
+control	O
+rats	O
+,	O
+intravenous	O
+bromocriptine	B-Chemical
+(	O
+150	O
+microg	O
+/	O
+kg	O
+)	O
+induced	O
+significant	O
+hypotension	B-Disease
+and	O
+tachycardia	B-Disease
+.	O
+
+Bromocriptine	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+was	O
+unaffected	O
+by	O
+isoproterenol	B-Chemical
+pretreatment	O
+,	O
+while	O
+tachycardia	B-Disease
+was	O
+reversed	O
+to	O
+significant	O
+bradycardia	B-Disease
+,	O
+an	O
+effect	O
+that	O
+was	O
+partly	O
+reduced	O
+by	O
+i	O
+.	O
+v	O
+.	O
+domperidone	B-Chemical
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+Neither	O
+cardiac	O
+vagal	O
+nor	O
+sympathetic	O
+tone	O
+was	O
+altered	O
+by	O
+isoproterenol	B-Chemical
+pretreatment	O
+.	O
+
+In	O
+isolated	O
+perfused	O
+heart	O
+preparations	O
+from	O
+isoproterenol	B-Chemical
+-	O
+pretreated	O
+rats	O
+,	O
+the	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+maximal	O
+increase	O
+in	O
+left	O
+ventricular	O
+systolic	O
+pressure	O
+was	O
+significantly	O
+reduced	O
+,	O
+compared	O
+with	O
+saline	O
+-	O
+pretreated	O
+rats	O
+(	O
+the	O
+EC50	O
+of	O
+the	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+increase	O
+in	O
+left	O
+ventricular	O
+systolic	O
+pressure	O
+was	O
+enhanced	O
+approximately	O
+22	O
+-	O
+fold	O
+)	O
+.	O
+
+These	O
+results	O
+show	O
+that	O
+15	O
+-	O
+day	O
+isoproterenol	B-Chemical
+pretreatment	O
+not	O
+only	O
+abolished	O
+but	O
+reversed	O
+bromocriptine	B-Chemical
+-	O
+induced	O
+tachycardia	B-Disease
+to	O
+bradycardia	B-Disease
+,	O
+an	O
+effect	O
+that	O
+is	O
+mainly	O
+related	O
+to	O
+further	O
+cardiac	O
+beta	O
+-	O
+adrenoceptor	O
+desensitization	O
+rather	O
+than	O
+to	O
+impairment	O
+of	O
+autonomic	O
+regulation	O
+of	O
+the	O
+heart	O
+.	O
+
+They	O
+suggest	O
+that	O
+,	O
+in	O
+normal	O
+conscious	O
+rats	O
+,	O
+the	O
+central	O
+tachycardia	B-Disease
+of	O
+bromocriptine	B-Chemical
+appears	O
+to	O
+predominate	O
+and	O
+to	O
+mask	O
+the	O
+bradycardia	B-Disease
+of	O
+this	O
+agonist	O
+at	O
+peripheral	O
+dopamine	B-Chemical
+D2	O
+receptors	O
+.	O
+
+A	O
+developmental	O
+analysis	O
+of	O
+clonidine	B-Chemical
+'	O
+s	O
+effects	O
+on	O
+cardiac	O
+rate	O
+and	O
+ultrasound	O
+production	O
+in	O
+infant	O
+rats	O
+.	O
+
+Under	O
+controlled	O
+conditions	O
+,	O
+infant	O
+rats	O
+emit	O
+ultrasonic	O
+vocalizations	O
+during	O
+extreme	O
+cold	O
+exposure	O
+and	O
+after	O
+administration	O
+of	O
+the	O
+alpha	O
+(	O
+2	O
+)	O
+adrenoceptor	O
+agonist	O
+,	O
+clonidine	B-Chemical
+.	O
+
+Previous	O
+investigations	O
+have	O
+determined	O
+that	O
+,	O
+in	O
+response	O
+to	O
+clonidine	B-Chemical
+,	O
+ultrasound	O
+production	O
+increases	O
+through	O
+the	O
+2nd	O
+-	O
+week	O
+postpartum	O
+and	O
+decreases	O
+thereafter	O
+.	O
+
+Given	O
+that	O
+sympathetic	O
+neural	O
+dominance	O
+exhibits	O
+a	O
+similar	O
+developmental	O
+pattern	O
+,	O
+and	O
+given	O
+that	O
+clonidine	B-Chemical
+induces	O
+sympathetic	O
+withdrawal	O
+and	O
+bradycardia	B-Disease
+,	O
+we	O
+hypothesized	O
+that	O
+clonidine	B-Chemical
+'	O
+s	O
+developmental	O
+effects	O
+on	O
+cardiac	O
+rate	O
+and	O
+ultrasound	O
+production	O
+would	O
+mirror	O
+each	O
+other	O
+.	O
+
+Therefore	O
+,	O
+in	O
+the	O
+present	O
+experiment	O
+,	O
+the	O
+effects	O
+of	O
+clonidine	B-Chemical
+administration	O
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+on	O
+cardiac	O
+rate	O
+and	O
+ultrasound	O
+production	O
+were	O
+examined	O
+in	O
+2	O
+-	O
+,	O
+8	O
+-	O
+,	O
+15	O
+-	O
+,	O
+and	O
+20	O
+-	O
+day	O
+-	O
+old	O
+rats	O
+.	O
+
+Age	O
+-	O
+related	O
+changes	O
+in	O
+ultrasound	O
+production	O
+corresponded	O
+with	O
+changes	O
+in	O
+cardiovascular	O
+variables	O
+,	O
+including	O
+baseline	O
+cardiac	O
+rate	O
+and	O
+clonidine	B-Chemical
+-	O
+induced	O
+bradycardia	B-Disease
+.	O
+
+This	O
+experiment	O
+is	O
+discussed	O
+with	O
+regard	O
+to	O
+the	O
+hypothesis	O
+that	O
+ultrasound	O
+production	O
+is	O
+the	O
+acoustic	O
+by	O
+-	O
+product	O
+of	O
+a	O
+physiological	O
+maneuver	O
+that	O
+compensates	O
+for	O
+clonidine	B-Chemical
+'	O
+s	O
+detrimental	O
+effects	O
+on	O
+cardiovascular	O
+function	O
+.	O
+
+Recurrent	O
+use	O
+of	O
+newer	O
+oral	B-Chemical
+contraceptives	I-Chemical
+and	O
+the	O
+risk	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+.	O
+
+The	O
+epidemiological	O
+studies	O
+that	O
+assessed	O
+the	O
+risk	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+(	O
+VTE	B-Disease
+)	O
+associated	O
+with	O
+newer	O
+oral	B-Chemical
+contraceptives	I-Chemical
+(	O
+OC	B-Chemical
+)	O
+did	O
+not	O
+distinguish	O
+between	O
+patterns	O
+of	O
+OC	B-Chemical
+use	O
+,	O
+namely	O
+first	O
+-	O
+time	O
+users	O
+,	O
+repeaters	O
+and	O
+switchers	O
+.	O
+
+Data	O
+from	O
+a	O
+Transnational	O
+case	O
+-	O
+control	O
+study	O
+were	O
+used	O
+to	O
+assess	O
+the	O
+risk	O
+of	O
+VTE	B-Disease
+for	O
+the	O
+latter	O
+patterns	O
+of	O
+use	O
+,	O
+while	O
+accounting	O
+for	O
+duration	O
+of	O
+use	O
+.	O
+
+Over	O
+the	O
+period	O
+1993	O
+-	O
+1996	O
+,	O
+551	O
+cases	O
+of	O
+VTE	B-Disease
+were	O
+identified	O
+in	O
+Germany	O
+and	O
+the	O
+UK	O
+along	O
+with	O
+2066	O
+controls	O
+.	O
+
+Totals	O
+of	O
+128	O
+cases	O
+and	O
+650	O
+controls	O
+were	O
+analysed	O
+for	O
+repeat	O
+use	O
+and	O
+135	O
+cases	O
+and	O
+622	O
+controls	O
+for	O
+switching	O
+patterns	O
+.	O
+
+The	O
+adjusted	O
+rate	O
+ratio	O
+of	O
+VTE	B-Disease
+for	O
+repeat	O
+users	O
+of	O
+third	O
+generation	O
+OC	B-Chemical
+was	O
+0	O
+.	O
+6	O
+(	O
+95	O
+%	O
+CI	O
+:	O
+0	O
+.	O
+3	O
+-	O
+1	O
+.	O
+2	O
+)	O
+relative	O
+to	O
+repeat	O
+users	O
+of	O
+second	O
+generation	O
+pills	O
+,	O
+whereas	O
+it	O
+was	O
+1	O
+.	O
+3	O
+(	O
+95	O
+%	O
+CI	O
+:	O
+0	O
+.	O
+7	O
+-	O
+2	O
+.	O
+4	O
+)	O
+for	O
+switchers	O
+from	O
+second	O
+to	O
+third	O
+generation	O
+pills	O
+relative	O
+to	O
+switchers	O
+from	O
+third	O
+to	O
+second	O
+generation	O
+pills	O
+.	O
+
+We	O
+conclude	O
+that	O
+second	O
+and	O
+third	O
+generation	O
+agents	O
+are	O
+associated	O
+with	O
+equivalent	O
+risks	O
+of	O
+VTE	B-Disease
+when	O
+the	O
+same	O
+agent	O
+is	O
+used	O
+repeatedly	O
+after	O
+interruption	O
+periods	O
+or	O
+when	O
+users	O
+are	O
+switched	O
+between	O
+the	O
+two	O
+generations	O
+of	O
+pills	O
+.	O
+
+These	O
+analyses	O
+suggest	O
+that	O
+the	O
+higher	O
+risk	O
+observed	O
+for	O
+the	O
+newer	O
+OC	B-Chemical
+in	O
+other	O
+studies	O
+may	O
+be	O
+the	O
+result	O
+of	O
+inadequate	O
+comparisons	O
+of	O
+pill	O
+users	O
+with	O
+different	O
+patterns	O
+of	O
+pill	O
+use	O
+.	O
+
+Differential	O
+effects	O
+of	O
+systemically	O
+administered	O
+ketamine	B-Chemical
+and	O
+lidocaine	B-Chemical
+on	O
+dynamic	O
+and	O
+static	O
+hyperalgesia	B-Disease
+induced	O
+by	O
+intradermal	O
+capsaicin	B-Chemical
+in	O
+humans	O
+.	O
+
+We	O
+have	O
+examined	O
+the	O
+effect	O
+of	O
+systemic	O
+administration	O
+of	O
+ketamine	B-Chemical
+and	O
+lidocaine	B-Chemical
+on	O
+brush	O
+-	O
+evoked	O
+(	O
+dynamic	O
+)	O
+pain	B-Disease
+and	O
+punctate	O
+-	O
+evoked	O
+(	O
+static	O
+)	O
+hyperalgesia	B-Disease
+induced	O
+by	O
+capsaicin	B-Chemical
+.	O
+
+In	O
+a	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+,	O
+crossover	O
+study	O
+,	O
+we	O
+studied	O
+12	O
+volunteers	O
+in	O
+three	O
+experiments	O
+.	O
+
+Capsaicin	B-Chemical
+100	O
+micrograms	O
+was	O
+injected	O
+intradermally	O
+on	O
+the	O
+volar	O
+forearm	O
+followed	O
+by	O
+an	O
+i	O
+.	O
+v	O
+.	O
+infusion	O
+of	O
+ketamine	B-Chemical
+(	O
+bolus	O
+0	O
+.	O
+1	O
+mg	O
+kg	O
+-	O
+1	O
+over	O
+10	O
+min	O
+followed	O
+by	O
+infusion	O
+of	O
+7	O
+micrograms	O
+kg	O
+-	O
+1	O
+min	O
+-	O
+1	O
+)	O
+,	O
+lidocaine	B-Chemical
+5	O
+mg	O
+kg	O
+-	O
+1	O
+or	O
+saline	O
+for	O
+50	O
+min	O
+.	O
+
+Infusion	O
+started	O
+15	O
+min	O
+after	O
+injection	O
+of	O
+capsaicin	B-Chemical
+.	O
+
+The	O
+following	O
+were	O
+measured	O
+:	O
+spontaneous	O
+pain	B-Disease
+,	O
+pain	B-Disease
+evoked	O
+by	O
+punctate	O
+and	O
+brush	O
+stimuli	O
+(	O
+VAS	O
+)	O
+,	O
+and	O
+areas	O
+of	O
+brush	O
+-	O
+evoked	O
+and	O
+punctate	O
+-	O
+evoked	O
+hyperalgesia	B-Disease
+.	O
+
+Ketamine	B-Chemical
+reduced	O
+both	O
+the	O
+area	O
+of	O
+brush	O
+-	O
+evoked	O
+and	O
+punctate	O
+-	O
+evoked	O
+hyperalgesia	B-Disease
+significantly	O
+and	O
+it	O
+tended	O
+to	O
+reduce	O
+brush	O
+-	O
+evoked	O
+pain	B-Disease
+.	O
+
+Lidocaine	B-Chemical
+reduced	O
+the	O
+area	O
+of	O
+punctate	O
+-	O
+evoked	O
+hyperalgesia	B-Disease
+significantly	O
+.	O
+
+It	O
+tended	O
+to	O
+reduce	O
+VAS	O
+scores	O
+of	O
+spontaneous	O
+pain	B-Disease
+but	O
+had	O
+no	O
+effect	O
+on	O
+evoked	O
+pain	B-Disease
+.	O
+
+The	O
+differential	O
+effects	O
+of	O
+ketamine	B-Chemical
+and	O
+lidocaine	B-Chemical
+on	O
+static	O
+and	O
+dynamic	O
+hyperalgesia	B-Disease
+suggest	O
+that	O
+the	O
+two	O
+types	O
+of	O
+hyperalgesia	B-Disease
+are	O
+mediated	O
+by	O
+separate	O
+mechanisms	O
+and	O
+have	O
+a	O
+distinct	O
+pharmacology	O
+.	O
+
+Development	O
+of	O
+apomorphine	B-Chemical
+-	O
+induced	O
+aggressive	B-Disease
+behavior	I-Disease
+:	O
+comparison	O
+of	O
+adult	O
+male	O
+and	O
+female	O
+Wistar	O
+rats	O
+.	O
+
+The	O
+development	O
+of	O
+apomorphine	B-Chemical
+-	O
+induced	O
+(	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+once	O
+daily	O
+)	O
+aggressive	B-Disease
+behavior	I-Disease
+of	O
+adult	O
+male	O
+and	O
+female	O
+Wistar	O
+rats	O
+obtained	O
+from	O
+the	O
+same	O
+breeder	O
+was	O
+studied	O
+in	O
+two	O
+consecutive	O
+sets	O
+.	O
+
+In	O
+male	O
+animals	O
+,	O
+repeated	O
+apomorphine	B-Chemical
+treatment	O
+induced	O
+a	O
+gradual	O
+development	O
+of	O
+aggressive	B-Disease
+behavior	I-Disease
+as	O
+evidenced	O
+by	O
+the	O
+increased	O
+intensity	O
+of	O
+aggressiveness	B-Disease
+and	O
+shortened	O
+latency	O
+before	O
+the	O
+first	O
+attack	O
+toward	O
+the	O
+opponent	O
+.	O
+
+In	O
+female	O
+rats	O
+,	O
+only	O
+a	O
+weak	O
+tendency	O
+toward	O
+aggressiveness	B-Disease
+was	O
+found	O
+.	O
+
+In	O
+conclusion	O
+,	O
+the	O
+present	O
+study	O
+demonstrates	O
+gender	O
+differences	O
+in	O
+the	O
+development	O
+of	O
+the	O
+apomorphine	B-Chemical
+-	O
+induced	O
+aggressive	B-Disease
+behavior	I-Disease
+and	O
+indicates	O
+that	O
+the	O
+female	O
+rats	O
+do	O
+not	O
+fill	O
+the	O
+validation	O
+criteria	O
+for	O
+use	O
+in	O
+this	O
+method	O
+.	O
+
+Intracranial	B-Disease
+aneurysms	I-Disease
+and	O
+cocaine	B-Disease
+abuse	I-Disease
+:	O
+analysis	O
+of	O
+prognostic	O
+indicators	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+outcome	O
+of	O
+subarachnoid	B-Disease
+hemorrhage	I-Disease
+associated	O
+with	O
+cocaine	B-Disease
+abuse	I-Disease
+is	O
+reportedly	O
+poor	O
+.	O
+
+However	O
+,	O
+no	O
+study	O
+in	O
+the	O
+literature	O
+has	O
+reported	O
+the	O
+use	O
+of	O
+a	O
+statistical	O
+model	O
+to	O
+analyze	O
+the	O
+variables	O
+that	O
+influence	O
+outcome	O
+.	O
+
+METHODS	O
+:	O
+A	O
+review	O
+of	O
+admissions	O
+during	O
+a	O
+6	O
+-	O
+year	O
+period	O
+revealed	O
+14	O
+patients	O
+with	O
+cocaine	B-Chemical
+-	O
+related	O
+aneurysms	B-Disease
+.	O
+
+This	O
+group	O
+was	O
+compared	O
+with	O
+a	O
+control	O
+group	O
+of	O
+135	O
+patients	O
+with	O
+ruptured	B-Disease
+aneurysms	I-Disease
+and	O
+no	O
+history	O
+of	O
+cocaine	B-Disease
+abuse	I-Disease
+.	O
+
+Age	O
+at	O
+presentation	O
+,	O
+time	O
+of	O
+ictus	O
+after	O
+intoxication	O
+,	O
+Hunt	O
+and	O
+Hess	O
+grade	O
+of	O
+subarachnoid	B-Disease
+hemorrhage	I-Disease
+,	O
+size	O
+of	O
+the	O
+aneurysm	B-Disease
+,	O
+location	O
+of	O
+the	O
+aneurysm	B-Disease
+,	O
+and	O
+the	O
+Glasgow	O
+Outcome	O
+Scale	O
+score	O
+were	O
+assessed	O
+and	O
+compared	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+patients	O
+in	O
+the	O
+study	O
+group	O
+were	O
+significantly	O
+younger	O
+than	O
+the	O
+patients	O
+in	O
+the	O
+control	O
+group	O
+(	O
+P	O
+<	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+In	O
+patients	O
+in	O
+the	O
+study	O
+group	O
+,	O
+all	O
+aneurysms	B-Disease
+were	O
+located	O
+in	O
+the	O
+anterior	O
+circulation	O
+.	O
+
+The	O
+majority	O
+of	O
+these	O
+aneurysms	B-Disease
+were	O
+smaller	O
+than	O
+those	O
+of	O
+the	O
+control	O
+group	O
+(	O
+8	O
++	O
+/	O
+-	O
+6	O
+.	O
+08	O
+mm	O
+versus	O
+11	O
++	O
+/	O
+-	O
+5	O
+.	O
+4	O
+mm	O
+;	O
+P	O
+=	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+differences	O
+in	O
+mortality	O
+and	O
+morbidity	O
+between	O
+the	O
+two	O
+groups	O
+were	O
+not	O
+significant	O
+.	O
+
+Hunt	O
+and	O
+Hess	O
+grade	O
+(	O
+P	O
+<	O
+0	O
+.	O
+005	O
+)	O
+and	O
+age	O
+(	O
+P	O
+<	O
+0	O
+.	O
+007	O
+)	O
+were	O
+significant	O
+predictors	O
+of	O
+outcome	O
+for	O
+the	O
+patients	O
+with	O
+cocaine	B-Chemical
+-	O
+related	O
+aneurysms	B-Disease
+.	O
+
+CONCLUSION	O
+:	O
+Cocaine	B-Chemical
+use	O
+predisposed	O
+aneurysmal	B-Disease
+rupture	I-Disease
+at	O
+a	O
+significantly	O
+earlier	O
+age	O
+and	O
+in	O
+much	O
+smaller	O
+aneurysms	B-Disease
+.	O
+
+Contrary	O
+to	O
+the	O
+published	O
+literature	O
+,	O
+this	O
+group	O
+did	O
+reasonably	O
+well	O
+with	O
+aggressive	O
+management	O
+.	O
+
+Effect	O
+of	O
+intravenous	O
+nimodipine	B-Chemical
+on	O
+blood	O
+pressure	O
+and	O
+outcome	O
+after	O
+acute	B-Disease
+stroke	I-Disease
+.	O
+
+BACKGROUND	O
+AND	O
+PURPOSE	O
+:	O
+The	O
+Intravenous	O
+Nimodipine	B-Chemical
+West	O
+European	O
+Stroke	B-Disease
+Trial	O
+(	O
+INWEST	O
+)	O
+found	O
+a	O
+correlation	O
+between	O
+nimodipine	B-Chemical
+-	O
+induced	O
+reduction	B-Disease
+in	I-Disease
+blood	I-Disease
+pressure	I-Disease
+(	O
+BP	O
+)	O
+and	O
+an	O
+unfavorable	O
+outcome	O
+in	O
+acute	B-Disease
+stroke	I-Disease
+.	O
+
+We	O
+sought	O
+to	O
+confirm	O
+this	O
+correlation	O
+with	O
+and	O
+without	O
+adjustment	O
+for	O
+prognostic	O
+variables	O
+and	O
+to	O
+investigate	O
+outcome	O
+in	O
+subgroups	O
+with	O
+increasing	O
+levels	O
+of	O
+BP	B-Disease
+reduction	I-Disease
+.	O
+
+METHODS	O
+:	O
+Patients	O
+with	O
+a	O
+clinical	O
+diagnosis	O
+of	O
+ischemic	B-Disease
+stroke	I-Disease
+(	O
+within	O
+24	O
+hours	O
+)	O
+were	O
+consecutively	O
+allocated	O
+to	O
+receive	O
+placebo	O
+(	O
+n	O
+=	O
+100	O
+)	O
+,	O
+1	O
+mg	O
+/	O
+h	O
+(	O
+low	O
+-	O
+dose	O
+)	O
+nimodipine	B-Chemical
+(	O
+n	O
+=	O
+101	O
+)	O
+,	O
+or	O
+2	O
+mg	O
+/	O
+h	O
+(	O
+high	O
+-	O
+dose	O
+)	O
+nimodipine	B-Chemical
+(	O
+n	O
+=	O
+94	O
+)	O
+.	O
+
+The	O
+correlation	O
+between	O
+average	O
+BP	O
+change	O
+during	O
+the	O
+first	O
+2	O
+days	O
+and	O
+the	O
+outcome	O
+at	O
+day	O
+21	O
+was	O
+analyzed	O
+.	O
+
+RESULTS	O
+:	O
+Two	O
+hundred	O
+sixty	O
+-	O
+five	O
+patients	O
+were	O
+included	O
+in	O
+this	O
+analysis	O
+(	O
+n	O
+=	O
+92	O
+,	O
+93	O
+,	O
+and	O
+80	O
+for	O
+placebo	O
+,	O
+low	O
+dose	O
+,	O
+and	O
+high	O
+dose	O
+,	O
+respectively	O
+)	O
+.	O
+
+Nimodipine	B-Chemical
+treatment	O
+resulted	O
+in	O
+a	O
+statistically	O
+significant	O
+reduction	B-Disease
+in	I-Disease
+systolic	I-Disease
+BP	I-Disease
+(	O
+SBP	O
+)	O
+and	O
+diastolic	O
+BP	O
+(	O
+DBP	O
+)	O
+from	O
+baseline	O
+compared	O
+with	O
+placebo	O
+during	O
+the	O
+first	O
+few	O
+days	O
+.	O
+
+In	O
+multivariate	O
+analysis	O
+,	O
+a	O
+significant	O
+correlation	O
+between	O
+DBP	B-Disease
+reduction	I-Disease
+and	O
+worsening	O
+of	O
+the	O
+neurological	O
+score	O
+was	O
+found	O
+for	O
+the	O
+high	O
+-	O
+dose	O
+group	O
+(	O
+beta	O
+=	O
+0	O
+.	O
+49	O
+,	O
+P	O
+=	O
+0	O
+.	O
+048	O
+)	O
+.	O
+
+Patients	O
+with	O
+a	O
+DBP	B-Disease
+reduction	I-Disease
+of	O
+>	O
+or	O
+=	O
+20	O
+%	O
+in	O
+the	O
+high	O
+-	O
+dose	O
+group	O
+had	O
+a	O
+significantly	O
+increased	O
+adjusted	O
+OR	O
+for	O
+the	O
+compound	O
+outcome	O
+variable	O
+death	B-Disease
+or	O
+dependency	O
+(	O
+Barthel	O
+Index	O
+<	O
+60	O
+)	O
+(	O
+n	O
+/	O
+N	O
+=	O
+25	O
+/	O
+26	O
+,	O
+OR	O
+10	O
+.	O
+16	O
+,	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+02	O
+to	O
+101	O
+.	O
+74	O
+)	O
+and	O
+death	B-Disease
+alone	O
+(	O
+n	O
+/	O
+N	O
+=	O
+9	O
+/	O
+26	O
+,	O
+OR	O
+4	O
+.	O
+336	O
+,	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+131	O
+16	O
+.	O
+619	O
+)	O
+compared	O
+with	O
+all	O
+placebo	O
+patients	O
+(	O
+n	O
+/	O
+N	O
+=	O
+62	O
+/	O
+92	O
+and	O
+14	O
+/	O
+92	O
+,	O
+respectively	O
+)	O
+.	O
+
+There	O
+was	O
+no	O
+correlation	O
+between	O
+SBP	O
+change	O
+and	O
+outcome	O
+.	O
+
+CONCLUSIONS	O
+:	O
+DBP	O
+,	O
+but	O
+not	O
+SBP	O
+,	O
+reduction	O
+was	O
+associated	O
+with	O
+neurological	O
+worsening	O
+after	O
+the	O
+intravenous	O
+administration	O
+of	O
+high	O
+-	O
+dose	O
+nimodipine	B-Chemical
+after	O
+acute	B-Disease
+stroke	I-Disease
+.	O
+
+For	O
+low	O
+-	O
+dose	O
+nimodipine	B-Chemical
+,	O
+the	O
+results	O
+were	O
+not	O
+conclusive	O
+.	O
+
+These	O
+results	O
+do	O
+not	O
+confirm	O
+or	O
+exclude	O
+a	O
+neuroprotective	O
+property	O
+of	O
+nimodipine	B-Chemical
+.	O
+
+Neonatal	O
+pyridoxine	B-Chemical
+responsive	O
+convulsions	B-Disease
+due	O
+to	O
+isoniazid	B-Chemical
+therapy	O
+.	O
+
+A	O
+17	O
+-	O
+day	O
+-	O
+old	O
+infant	O
+on	O
+isoniazid	B-Chemical
+therapy	O
+13	O
+mg	O
+/	O
+kg	O
+daily	O
+from	O
+birth	O
+because	O
+of	O
+maternal	O
+tuberculosis	B-Disease
+was	O
+admitted	O
+after	O
+4	O
+days	O
+of	O
+clonic	B-Disease
+fits	I-Disease
+.	O
+
+No	O
+underlying	O
+infective	O
+or	O
+biochemical	O
+cause	O
+could	O
+be	O
+found	O
+.	O
+
+The	O
+fits	B-Disease
+ceased	O
+within	O
+4	O
+hours	O
+of	O
+administering	O
+intramuscular	O
+pyridoxine	B-Chemical
+,	O
+suggesting	O
+an	O
+aetiology	O
+of	O
+pyridoxine	B-Chemical
+deficiency	O
+secondary	O
+to	O
+isoniazid	B-Chemical
+medication	O
+.	O
+
+Ketamine	B-Chemical
+sedation	O
+for	O
+the	O
+reduction	O
+of	O
+children	O
+'	O
+s	O
+fractures	B-Disease
+in	O
+the	O
+emergency	O
+department	O
+.	O
+
+BACKGROUND	O
+:	O
+There	O
+recently	O
+has	O
+been	O
+a	O
+resurgence	O
+in	O
+the	O
+utilization	O
+of	O
+ketamine	B-Chemical
+,	O
+a	O
+unique	O
+anesthetic	O
+,	O
+for	O
+emergency	O
+-	O
+department	O
+procedures	O
+requiring	O
+sedation	O
+.	O
+
+The	O
+purpose	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+examine	O
+the	O
+safety	O
+and	O
+efficacy	O
+of	O
+ketamine	B-Chemical
+for	O
+sedation	O
+in	O
+the	O
+treatment	O
+of	O
+children	O
+'	O
+s	O
+fractures	B-Disease
+in	O
+the	O
+emergency	O
+department	O
+.	O
+
+METHODS	O
+:	O
+One	O
+hundred	O
+and	O
+fourteen	O
+children	O
+(	O
+average	O
+age	O
+,	O
+5	O
+.	O
+3	O
+years	O
+;	O
+range	O
+,	O
+twelve	O
+months	O
+to	O
+ten	O
+years	O
+and	O
+ten	O
+months	O
+)	O
+who	O
+underwent	O
+closed	O
+reduction	O
+of	O
+an	O
+isolated	O
+fracture	B-Disease
+or	O
+dislocation	B-Disease
+in	O
+the	O
+emergency	O
+department	O
+at	O
+a	O
+level	O
+-	O
+I	O
+trauma	B-Disease
+center	O
+were	O
+prospectively	O
+evaluated	O
+.	O
+
+Ketamine	B-Chemical
+hydrochloride	I-Chemical
+was	O
+administered	O
+intravenously	O
+(	O
+at	O
+a	O
+dose	O
+of	O
+two	O
+milligrams	O
+per	O
+kilogram	O
+of	O
+body	O
+weight	O
+)	O
+in	O
+ninety	O
+-	O
+nine	O
+of	O
+the	O
+patients	O
+and	O
+intramuscularly	O
+(	O
+at	O
+a	O
+dose	O
+of	O
+four	O
+milligrams	O
+per	O
+kilogram	O
+of	O
+body	O
+weight	O
+)	O
+in	O
+the	O
+other	O
+fifteen	O
+.	O
+
+A	O
+board	O
+-	O
+certified	O
+emergency	O
+physician	O
+skilled	O
+in	O
+airway	O
+management	O
+supervised	O
+administration	O
+of	O
+the	O
+anesthetic	O
+,	O
+and	O
+the	O
+patients	O
+were	O
+monitored	O
+by	O
+a	O
+registered	O
+nurse	O
+.	O
+
+Any	O
+pain	B-Disease
+during	O
+the	O
+reduction	O
+was	O
+rated	O
+by	O
+the	O
+orthopaedic	O
+surgeon	O
+treating	O
+the	O
+patient	O
+according	O
+to	O
+the	O
+Children	O
+'	O
+s	O
+Hospital	O
+of	O
+Eastern	O
+Ontario	O
+Pain	B-Disease
+Scale	O
+(	O
+CHEOPS	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+average	O
+time	O
+from	O
+intravenous	O
+administration	O
+of	O
+ketamine	B-Chemical
+to	O
+manipulation	O
+of	O
+the	O
+fracture	B-Disease
+or	O
+dislocation	B-Disease
+was	O
+one	O
+minute	O
+and	O
+thirty	O
+-	O
+six	O
+seconds	O
+(	O
+range	O
+,	O
+twenty	O
+seconds	O
+to	O
+five	O
+minutes	O
+)	O
+,	O
+and	O
+the	O
+average	O
+time	O
+from	O
+intramuscular	O
+administration	O
+to	O
+manipulation	O
+was	O
+four	O
+minutes	O
+and	O
+forty	O
+-	O
+two	O
+seconds	O
+(	O
+range	O
+,	O
+sixty	O
+seconds	O
+to	O
+fifteen	O
+minutes	O
+)	O
+.	O
+
+The	O
+average	O
+score	O
+according	O
+to	O
+the	O
+Children	O
+'	O
+s	O
+Hospital	O
+of	O
+Eastern	O
+Ontario	O
+Pain	B-Disease
+Scale	O
+was	O
+6	O
+.	O
+4	O
+points	O
+(	O
+range	O
+,	O
+5	O
+to	O
+10	O
+points	O
+)	O
+,	O
+reflecting	O
+minimal	O
+or	O
+no	O
+pain	B-Disease
+during	O
+fracture	B-Disease
+reduction	O
+.	O
+
+Adequate	O
+fracture	B-Disease
+reduction	O
+was	O
+obtained	O
+in	O
+111	O
+of	O
+the	O
+children	O
+.	O
+
+Ninety	O
+-	O
+nine	O
+percent	O
+(	O
+sixty	O
+-	O
+eight	O
+)	O
+of	O
+the	O
+sixty	O
+-	O
+nine	O
+parents	O
+present	O
+during	O
+the	O
+reduction	O
+were	O
+pleased	O
+with	O
+the	O
+sedation	O
+and	O
+would	O
+allow	O
+it	O
+to	O
+be	O
+used	O
+again	O
+in	O
+a	O
+similar	O
+situation	O
+.	O
+
+Patency	O
+of	O
+the	O
+airway	O
+and	O
+independent	O
+respiration	O
+were	O
+maintained	O
+in	O
+all	O
+of	O
+the	O
+patients	O
+.	O
+
+Blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+remained	O
+stable	O
+.	O
+
+Minor	O
+side	O
+effects	O
+included	O
+nausea	B-Disease
+(	O
+thirteen	O
+patients	O
+)	O
+,	O
+emesis	B-Disease
+(	O
+eight	O
+of	O
+the	O
+thirteen	O
+patients	O
+with	O
+nausea	B-Disease
+)	O
+,	O
+clumsiness	B-Disease
+(	O
+evident	O
+as	O
+ataxic	B-Disease
+movements	I-Disease
+in	O
+ten	O
+patients	O
+)	O
+,	O
+and	O
+dysphoric	B-Disease
+reaction	I-Disease
+(	O
+one	O
+patient	O
+)	O
+.	O
+
+No	O
+long	O
+-	O
+term	O
+sequelae	O
+were	O
+noted	O
+,	O
+and	O
+no	O
+patients	O
+had	O
+hallucinations	B-Disease
+or	O
+nightmares	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Ketamine	B-Chemical
+reliably	O
+,	O
+safely	O
+,	O
+and	O
+quickly	O
+provided	O
+adequate	O
+sedation	O
+to	O
+effectively	O
+facilitate	O
+the	O
+reduction	O
+of	O
+children	O
+'	O
+s	O
+fractures	B-Disease
+in	O
+the	O
+emergency	O
+department	O
+at	O
+our	O
+institution	O
+.	O
+
+Ketamine	B-Chemical
+should	O
+only	O
+be	O
+used	O
+in	O
+an	O
+environment	O
+such	O
+as	O
+the	O
+emergency	O
+department	O
+,	O
+where	O
+proper	O
+one	O
+-	O
+on	O
+-	O
+one	O
+monitoring	O
+is	O
+used	O
+and	O
+board	O
+-	O
+certified	O
+physicians	O
+skilled	O
+in	O
+airway	O
+management	O
+are	O
+directly	O
+involved	O
+in	O
+the	O
+care	O
+of	O
+the	O
+patient	O
+.	O
+
+Cyclosporine	B-Chemical
+and	O
+tacrolimus	B-Chemical
+-	O
+associated	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+.	O
+
+The	O
+development	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+(	O
+TMA	B-Disease
+)	O
+associated	O
+with	O
+the	O
+use	O
+of	O
+cyclosporine	B-Chemical
+has	O
+been	O
+well	O
+documented	O
+.	O
+
+Treatments	O
+have	O
+included	O
+discontinuation	O
+or	O
+reduction	O
+of	O
+cyclosporine	B-Chemical
+dose	O
+with	O
+or	O
+without	O
+concurrent	O
+plasma	O
+exchange	O
+,	O
+plasma	O
+infusion	O
+,	O
+anticoagulation	O
+,	O
+and	O
+intravenous	O
+immunoglobulin	O
+G	O
+infusion	O
+.	O
+
+However	O
+,	O
+for	O
+recipients	O
+of	O
+organ	O
+transplantation	O
+,	O
+removing	O
+the	O
+inciting	O
+agent	O
+is	O
+not	O
+without	O
+the	O
+attendant	O
+risk	O
+of	O
+precipitating	O
+acute	O
+rejection	O
+and	O
+graft	O
+loss	O
+.	O
+
+The	O
+last	O
+decade	O
+has	O
+seen	O
+the	O
+emergence	O
+of	O
+tacrolimus	B-Chemical
+as	O
+a	O
+potent	O
+immunosuppressive	O
+agent	O
+with	O
+mechanisms	O
+of	O
+action	O
+virtually	O
+identical	O
+to	O
+those	O
+of	O
+cyclosporine	B-Chemical
+.	O
+
+As	O
+a	O
+result	O
+,	O
+switching	O
+to	O
+tacrolimus	B-Chemical
+has	O
+been	O
+reported	O
+to	O
+be	O
+a	O
+viable	O
+therapeutic	O
+option	O
+in	O
+the	O
+setting	O
+of	O
+cyclosporine	B-Chemical
+-	O
+induced	O
+TMA	B-Disease
+.	O
+
+With	O
+the	O
+more	O
+widespread	O
+application	O
+of	O
+tacrolimus	B-Chemical
+in	O
+organ	O
+transplantation	O
+,	O
+tacrolimus	B-Chemical
+-	O
+associated	O
+TMA	B-Disease
+has	O
+also	O
+been	O
+recognized	O
+.	O
+
+However	O
+,	O
+literature	O
+regarding	O
+the	O
+incidence	O
+of	O
+the	O
+recurrence	O
+of	O
+TMA	B-Disease
+in	O
+patients	O
+exposed	O
+sequentially	O
+to	O
+cyclosporine	B-Chemical
+and	O
+tacrolimus	B-Chemical
+is	O
+limited	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+a	O
+living	O
+donor	O
+renal	O
+transplant	O
+recipient	O
+who	O
+developed	O
+cyclosporine	B-Chemical
+-	O
+induced	O
+TMA	B-Disease
+that	O
+responded	O
+to	O
+the	O
+withdrawal	O
+of	O
+cyclosporine	B-Chemical
+in	O
+conjunction	O
+with	O
+plasmapheresis	O
+and	O
+fresh	O
+frozen	O
+plasma	O
+replacement	O
+therapy	O
+.	O
+
+Introduction	O
+of	O
+tacrolimus	B-Chemical
+as	O
+an	O
+alternative	O
+immunosuppressive	O
+agent	O
+resulted	O
+in	O
+the	O
+recurrence	O
+of	O
+TMA	B-Disease
+and	O
+the	O
+subsequent	O
+loss	O
+of	O
+the	O
+renal	O
+allograft	O
+.	O
+
+Patients	O
+who	O
+are	O
+switched	O
+from	O
+cyclosporine	B-Chemical
+to	O
+tacrolimus	B-Chemical
+or	O
+vice	O
+versa	O
+should	O
+be	O
+closely	O
+monitored	O
+for	O
+the	O
+signs	O
+and	O
+symptoms	O
+of	O
+recurrent	O
+TMA	B-Disease
+.	O
+
+Analgesic	O
+effect	O
+of	O
+intravenous	O
+ketamine	B-Chemical
+in	O
+cancer	B-Disease
+patients	O
+on	O
+morphine	B-Chemical
+therapy	O
+:	O
+a	O
+randomized	O
+,	O
+controlled	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+crossover	O
+,	O
+double	O
+-	O
+dose	O
+study	O
+.	O
+
+Pain	B-Disease
+not	O
+responsive	O
+to	O
+morphine	B-Chemical
+is	O
+often	O
+problematic	O
+.	O
+
+Animal	O
+and	O
+clinical	O
+studies	O
+have	O
+suggested	O
+that	O
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+D	I-Chemical
+-	I-Chemical
+aspartate	I-Chemical
+(	O
+NMDA	B-Chemical
+)	O
+antagonists	O
+,	O
+such	O
+as	O
+ketamine	B-Chemical
+,	O
+may	O
+be	O
+effective	O
+in	O
+improving	O
+opioid	O
+analgesia	O
+in	O
+difficult	O
+pain	B-Disease
+syndromes	O
+,	O
+such	O
+as	O
+neuropathic	B-Disease
+pain	I-Disease
+.	O
+
+A	O
+slow	O
+bolus	O
+of	O
+subhypnotic	O
+doses	O
+of	O
+ketamine	B-Chemical
+(	O
+0	O
+.	O
+25	O
+mg	O
+/	O
+kg	O
+or	O
+0	O
+.	O
+50	O
+mg	O
+/	O
+kg	O
+)	O
+was	O
+given	O
+to	O
+10	O
+cancer	B-Disease
+patients	O
+whose	O
+pain	B-Disease
+was	O
+unrelieved	O
+by	O
+morphine	B-Chemical
+in	O
+a	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+crossover	O
+,	O
+double	O
+-	O
+dose	O
+study	O
+.	O
+
+Pain	B-Disease
+intensity	O
+on	O
+a	O
+0	O
+to	O
+10	O
+numerical	O
+scale	O
+;	O
+nausea	B-Disease
+and	O
+vomiting	B-Disease
+,	O
+drowsiness	O
+,	O
+confusion	B-Disease
+,	O
+and	O
+dry	B-Disease
+mouth	I-Disease
+,	O
+using	O
+a	O
+scale	O
+from	O
+0	O
+to	O
+3	O
+(	O
+not	O
+at	O
+all	O
+,	O
+slight	O
+,	O
+a	O
+lot	O
+,	O
+awful	O
+)	O
+;	O
+Mini	O
+-	O
+Mental	O
+State	O
+Examination	O
+(	O
+MMSE	O
+)	O
+(	O
+0	O
+-	O
+30	O
+)	O
+;	O
+and	O
+arterial	O
+pressure	O
+were	O
+recorded	O
+before	O
+administration	O
+of	O
+drugs	O
+(	O
+T0	O
+)	O
+and	O
+after	O
+30	O
+minutes	O
+(	O
+T30	O
+)	O
+,	O
+60	O
+minutes	O
+(	O
+T60	O
+)	O
+,	O
+120	O
+minutes	O
+(	O
+T120	O
+)	O
+,	O
+and	O
+180	O
+minutes	O
+(	O
+T180	O
+)	O
+.	O
+
+Ketamine	B-Chemical
+,	O
+but	O
+not	O
+saline	O
+solution	O
+,	O
+significantly	O
+reduced	O
+the	O
+pain	B-Disease
+intensity	O
+in	O
+almost	O
+all	O
+the	O
+patients	O
+at	O
+both	O
+doses	O
+.	O
+
+This	O
+effect	O
+was	O
+more	O
+relevant	O
+in	O
+patients	O
+treated	O
+with	O
+higher	O
+doses	O
+.	O
+
+Hallucinations	B-Disease
+occurred	O
+in	O
+4	O
+patients	O
+,	O
+and	O
+an	O
+unpleasant	O
+sensation	O
+(	O
+"	O
+empty	O
+head	O
+"	O
+)	O
+was	O
+also	O
+reported	O
+by	O
+2	O
+patients	O
+.	O
+
+These	O
+episodes	O
+reversed	O
+after	O
+the	O
+administration	O
+of	O
+diazepam	B-Chemical
+1	O
+mg	O
+intravenously	O
+.	O
+
+Significant	O
+increases	O
+in	O
+drowsiness	O
+were	O
+reported	O
+in	O
+patients	O
+treated	O
+with	O
+ketamine	B-Chemical
+in	O
+both	O
+groups	O
+and	O
+were	O
+more	O
+marked	O
+with	O
+ketamine	B-Chemical
+0	O
+.	O
+50	O
+mg	O
+/	O
+kg	O
+.	O
+
+A	O
+significant	O
+difference	O
+in	O
+MMSE	O
+was	O
+observed	O
+at	O
+T30	O
+in	O
+patients	O
+who	O
+received	O
+0	O
+.	O
+50	O
+mg	O
+/	O
+kg	O
+of	O
+ketamine	B-Chemical
+.	O
+
+Ketamine	B-Chemical
+can	O
+improve	O
+morphine	B-Chemical
+analgesia	O
+in	O
+difficult	O
+pain	B-Disease
+syndromes	O
+,	O
+such	O
+as	O
+neuropathic	B-Disease
+pain	I-Disease
+.	O
+
+However	O
+,	O
+the	O
+occurrence	O
+of	O
+central	O
+adverse	O
+effects	O
+should	O
+be	O
+taken	O
+into	O
+account	O
+,	O
+especially	O
+when	O
+using	O
+higher	O
+doses	O
+.	O
+
+This	O
+observation	O
+should	O
+be	O
+tested	O
+in	O
+studies	O
+of	O
+prolonged	O
+ketamine	B-Chemical
+administration	O
+.	O
+
+Paclitaxel	B-Chemical
+,	O
+cisplatin	B-Chemical
+,	O
+and	O
+gemcitabine	B-Chemical
+combination	O
+chemotherapy	O
+within	O
+a	O
+multidisciplinary	O
+therapeutic	O
+approach	O
+in	O
+metastatic	O
+nonsmall	B-Disease
+cell	I-Disease
+lung	I-Disease
+carcinoma	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Cisplatin	B-Chemical
+-	O
+based	O
+chemotherapy	O
+combinations	O
+improve	O
+quality	O
+of	O
+life	O
+and	O
+survival	O
+in	O
+advanced	O
+nonsmall	B-Disease
+cell	I-Disease
+lung	I-Disease
+carcinoma	I-Disease
+(	O
+NSCLC	B-Disease
+)	O
+.	O
+
+The	O
+emergence	O
+of	O
+new	O
+active	O
+drugs	O
+might	O
+translate	O
+into	O
+more	O
+effective	O
+regimens	O
+for	O
+the	O
+treatment	O
+of	O
+this	O
+disease	O
+.	O
+
+METHODS	O
+:	O
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+feasibility	O
+,	O
+response	O
+rate	O
+,	O
+and	O
+toxicity	B-Disease
+of	O
+a	O
+paclitaxel	B-Chemical
+,	O
+cisplatin	B-Chemical
+,	O
+and	O
+gemcitabine	B-Chemical
+combination	O
+to	O
+treat	O
+metastatic	O
+NSCLC	B-Disease
+.	O
+
+Thirty	O
+-	O
+five	O
+consecutive	O
+chemotherapy	O
+-	O
+naive	O
+patients	O
+with	O
+Stage	O
+IV	O
+NSCLC	B-Disease
+and	O
+an	O
+Eastern	O
+Cooperative	O
+Oncology	O
+Group	O
+performance	O
+status	O
+of	O
+0	O
+-	O
+2	O
+were	O
+treated	O
+with	O
+a	O
+combination	O
+of	O
+paclitaxel	B-Chemical
+(	O
+135	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+given	O
+intravenously	O
+in	O
+3	O
+hours	O
+)	O
+on	O
+Day	O
+1	O
+,	O
+cisplatin	B-Chemical
+(	O
+120	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+given	O
+intravenously	O
+in	O
+6	O
+hours	O
+)	O
+on	O
+Day	O
+1	O
+,	O
+and	O
+gemcitabine	B-Chemical
+(	O
+800	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+given	O
+intravenously	O
+in	O
+30	O
+minutes	O
+)	O
+on	O
+Days	O
+1	O
+and	O
+8	O
+,	O
+every	O
+4	O
+weeks	O
+.	O
+
+Although	O
+responding	O
+patients	O
+were	O
+scheduled	O
+to	O
+receive	O
+consolidation	O
+radiotherapy	O
+and	O
+24	O
+patients	O
+received	O
+preplanned	O
+second	O
+-	O
+line	O
+chemotherapy	O
+after	O
+disease	O
+progression	O
+,	O
+the	O
+response	O
+and	O
+toxicity	B-Disease
+rates	O
+reported	O
+refer	O
+only	O
+to	O
+the	O
+chemotherapy	O
+regimen	O
+given	O
+.	O
+
+RESULTS	O
+:	O
+All	O
+the	O
+patients	O
+were	O
+examined	O
+for	O
+toxicity	B-Disease
+;	O
+34	O
+were	O
+examinable	O
+for	O
+response	O
+.	O
+
+An	O
+objective	O
+response	O
+was	O
+observed	O
+in	O
+73	O
+.	O
+5	O
+%	O
+of	O
+the	O
+patients	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+,	O
+55	O
+.	O
+6	O
+-	O
+87	O
+.	O
+1	O
+%	O
+)	O
+,	O
+including	O
+4	O
+complete	O
+responses	O
+(	O
+11	O
+.	O
+7	O
+%	O
+)	O
+.	O
+
+According	O
+to	O
+intention	O
+-	O
+to	O
+-	O
+treat	O
+,	O
+the	O
+overall	O
+response	O
+rate	O
+was	O
+71	O
+.	O
+4	O
+%	O
+(	O
+95	O
+%	O
+CI	O
+,	O
+53	O
+.	O
+7	O
+-	O
+85	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+After	O
+154	O
+courses	O
+of	O
+therapy	O
+,	O
+the	O
+median	O
+dose	O
+intensity	O
+was	O
+131	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+for	O
+paclitaxel	B-Chemical
+(	O
+97	O
+.	O
+3	O
+%	O
+)	O
+,	O
+117	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+for	O
+cisplatin	B-Chemical
+(	O
+97	O
+.	O
+3	O
+%	O
+)	O
+,	O
+and	O
+1378	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+for	O
+gemcitabine	B-Chemical
+(	O
+86	O
+.	O
+2	O
+%	O
+)	O
+.	O
+
+World	O
+Health	O
+Organization	O
+Grade	O
+3	O
+-	O
+4	O
+neutropenia	B-Disease
+and	O
+thrombocytopenia	B-Disease
+occurred	O
+in	O
+39	O
+.	O
+9	O
+%	O
+and	O
+11	O
+.	O
+4	O
+%	O
+of	O
+patients	O
+,	O
+respectively	O
+.	O
+
+There	O
+was	O
+one	O
+treatment	O
+-	O
+related	O
+death	B-Disease
+.	O
+
+Nonhematologic	O
+toxicities	B-Disease
+were	O
+mild	O
+.	O
+
+After	O
+a	O
+median	O
+follow	O
+-	O
+up	O
+of	O
+22	O
+months	O
+,	O
+the	O
+median	O
+progression	O
+free	O
+survival	O
+rate	O
+was	O
+7	O
+months	O
+,	O
+and	O
+the	O
+median	O
+survival	O
+time	O
+was	O
+16	O
+months	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+combination	O
+of	O
+paclitaxel	B-Chemical
+,	O
+cisplatin	B-Chemical
+,	O
+and	O
+gemcitabine	B-Chemical
+is	O
+well	O
+tolerated	O
+and	O
+shows	O
+high	O
+activity	O
+in	O
+metastatic	O
+NSCLC	B-Disease
+.	O
+
+This	O
+treatment	O
+merits	O
+further	O
+comparison	O
+with	O
+other	O
+cisplatin	B-Chemical
+-	O
+based	O
+regimens	O
+.	O
+
+Serotonergic	B-Chemical
+antidepressants	I-Chemical
+and	O
+urinary	B-Disease
+incontinence	I-Disease
+.	O
+
+Many	O
+new	O
+serotonergic	B-Chemical
+antidepressants	I-Chemical
+have	O
+been	O
+introduced	O
+over	O
+the	O
+past	O
+decade	O
+.	O
+
+Although	O
+urinary	B-Disease
+incontinence	I-Disease
+is	O
+listed	O
+as	O
+one	O
+side	O
+effect	O
+of	O
+these	O
+drugs	O
+in	O
+their	O
+package	O
+inserts	O
+there	O
+is	O
+only	O
+one	O
+report	O
+in	O
+the	O
+literature	O
+.	O
+
+This	O
+concerns	O
+2	O
+male	O
+patients	O
+who	O
+experienced	O
+incontinence	B-Disease
+while	O
+taking	O
+venlafaxine	B-Chemical
+.	O
+
+In	O
+the	O
+present	O
+paper	O
+the	O
+authors	O
+describe	O
+2	O
+female	O
+patients	O
+who	O
+developed	O
+incontinence	B-Disease
+secondary	O
+to	O
+the	O
+selective	O
+serotonin	B-Chemical
+reuptake	O
+inhibitors	O
+paroxetine	B-Chemical
+and	O
+sertraline	B-Chemical
+,	O
+as	O
+well	O
+as	O
+a	O
+third	O
+who	O
+developed	O
+this	O
+side	O
+effect	O
+on	O
+venlafaxine	B-Chemical
+.	O
+
+In	O
+2	O
+of	O
+the	O
+3	O
+cases	O
+the	O
+patients	O
+were	O
+also	O
+taking	O
+lithium	B-Chemical
+carbonate	I-Chemical
+and	O
+beta	O
+-	O
+blockers	O
+,	O
+both	O
+of	O
+which	O
+could	O
+have	O
+contributed	O
+to	O
+the	O
+incontinence	B-Disease
+.	O
+
+Animal	O
+studies	O
+suggest	O
+that	O
+incontinence	B-Disease
+secondary	O
+to	O
+serotonergic	B-Chemical
+antidepressants	I-Chemical
+could	O
+be	O
+mediated	O
+by	O
+the	O
+5HT4	O
+receptors	O
+found	O
+on	O
+the	O
+bladder	O
+.	O
+
+Further	O
+research	O
+is	O
+needed	O
+to	O
+delineate	O
+the	O
+frequency	O
+of	O
+this	O
+troubling	O
+side	O
+effect	O
+and	O
+how	O
+best	O
+to	O
+treat	O
+it	O
+.	O
+
+Acute	O
+cocaine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+:	O
+differential	O
+sensitivity	O
+of	O
+six	O
+inbred	O
+mouse	O
+strains	O
+.	O
+
+Mature	O
+male	O
+and	O
+female	O
+mice	O
+from	O
+six	O
+inbred	O
+stains	O
+were	O
+tested	O
+for	O
+susceptibility	O
+to	O
+behavioral	O
+seizures	B-Disease
+induced	O
+by	O
+a	O
+single	O
+injection	O
+of	O
+cocaine	B-Chemical
+.	O
+
+Cocaine	B-Chemical
+was	O
+injected	O
+ip	O
+over	O
+a	O
+range	O
+of	O
+doses	O
+(	O
+50	O
+-	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+behavior	O
+was	O
+monitored	O
+for	O
+20	O
+minutes	O
+.	O
+
+Seizure	B-Disease
+end	O
+points	O
+included	O
+latency	O
+to	O
+forelimb	O
+or	O
+hindlimb	O
+clonus	O
+,	O
+latency	O
+to	O
+clonic	O
+running	O
+seizure	B-Disease
+and	O
+latency	O
+to	O
+jumping	O
+bouncing	O
+seizure	B-Disease
+.	O
+
+A	O
+range	O
+of	O
+strain	O
+specific	O
+sensitivities	O
+was	O
+documented	O
+with	O
+A	O
+/	O
+J	O
+and	O
+SJL	O
+mice	O
+being	O
+most	O
+sensitive	O
+and	O
+C57BL	O
+/	O
+6J	O
+most	O
+resistant	O
+.	O
+
+DBA	O
+/	O
+2J	O
+,	O
+BALB	O
+/	O
+cByJ	O
+and	O
+NZW	O
+/	O
+LacJ	O
+strains	O
+exhibited	O
+intermediate	O
+sensitivity	O
+.	O
+
+EEG	O
+recordings	O
+were	O
+made	O
+in	O
+SJL	O
+,	O
+A	O
+/	O
+J	O
+and	O
+C57BL	O
+/	O
+6J	O
+mice	O
+revealing	O
+a	O
+close	O
+correspondence	O
+between	O
+electrical	O
+activity	O
+and	O
+behavior	O
+.	O
+
+Additionally	O
+,	O
+levels	O
+of	O
+cocaine	B-Chemical
+determined	O
+in	O
+hippocampus	O
+and	O
+cortex	O
+were	O
+not	O
+different	O
+between	O
+sensitive	O
+and	O
+resistant	O
+strains	O
+.	O
+
+Additional	O
+studies	O
+of	O
+these	O
+murine	O
+strains	O
+may	O
+be	O
+useful	O
+for	O
+investigating	O
+genetic	O
+influences	O
+on	O
+cocaine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+.	O
+
+Hypotension	B-Disease
+following	O
+the	O
+initiation	O
+of	O
+tizanidine	B-Chemical
+in	O
+a	O
+patient	O
+treated	O
+with	O
+an	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+inhibitor	O
+for	O
+chronic	O
+hypertension	B-Disease
+.	O
+
+Centrally	O
+acting	O
+alpha	O
+-	O
+2	O
+adrenergic	O
+agonists	O
+are	O
+one	O
+of	O
+several	O
+pharmacologic	O
+agents	O
+used	O
+in	O
+the	O
+treatment	O
+of	O
+spasticity	B-Disease
+related	O
+to	O
+disorders	B-Disease
+of	I-Disease
+the	I-Disease
+central	I-Disease
+nervous	I-Disease
+system	I-Disease
+.	O
+
+In	O
+addition	O
+to	O
+their	O
+effects	O
+on	O
+spasticity	B-Disease
+,	O
+certain	O
+adverse	O
+cardiorespiratory	O
+effects	O
+have	O
+been	O
+reported	O
+.	O
+
+Adults	O
+chronically	O
+treated	O
+with	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+inhibitors	O
+may	O
+have	O
+a	O
+limited	O
+ability	O
+to	O
+respond	O
+to	O
+hypotension	B-Disease
+when	O
+the	O
+sympathetic	O
+response	O
+is	O
+simultaneously	O
+blocked	O
+.	O
+
+The	O
+authors	O
+present	O
+a	O
+10	O
+-	O
+year	O
+-	O
+old	O
+boy	O
+chronically	O
+treated	O
+with	O
+lisinopril	B-Chemical
+,	O
+an	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+inhibitor	O
+,	O
+to	O
+control	O
+hypertension	B-Disease
+who	O
+developed	O
+hypotension	B-Disease
+following	O
+the	O
+addition	O
+of	O
+tizanidine	B-Chemical
+,	O
+an	O
+alpha	O
+-	O
+2	O
+agonist	O
+,	O
+for	O
+the	O
+treatment	O
+of	O
+spasticity	B-Disease
+.	O
+
+The	O
+possible	O
+interaction	O
+of	O
+tizanidine	B-Chemical
+and	O
+other	O
+antihypertensive	O
+agents	O
+should	O
+be	O
+kept	O
+in	O
+mind	O
+when	O
+prescribing	O
+therapy	O
+to	O
+treat	O
+either	O
+hypertension	B-Disease
+or	O
+spasticity	B-Disease
+in	O
+such	O
+patients	O
+.	O
+
+Two	O
+mouse	O
+lines	O
+selected	O
+for	O
+differential	O
+sensitivities	O
+to	O
+beta	B-Chemical
+-	I-Chemical
+carboline	I-Chemical
+-	O
+induced	O
+seizures	B-Disease
+are	O
+also	O
+differentially	O
+sensitive	O
+to	O
+various	O
+pharmacological	O
+effects	O
+of	O
+other	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+receptor	O
+ligands	O
+.	O
+
+Two	O
+mouse	O
+lines	O
+were	O
+selectively	O
+bred	O
+according	O
+to	O
+their	O
+sensitivity	O
+(	O
+BS	O
+line	O
+)	O
+or	O
+resistance	O
+(	O
+BR	O
+line	O
+)	O
+to	O
+seizures	B-Disease
+induced	O
+by	O
+a	O
+single	O
+i	O
+.	O
+p	O
+.	O
+injection	O
+of	O
+methyl	B-Chemical
+beta	I-Chemical
+-	I-Chemical
+carboline	I-Chemical
+-	I-Chemical
+3	I-Chemical
+-	I-Chemical
+carboxylate	I-Chemical
+(	O
+beta	B-Chemical
+-	I-Chemical
+CCM	I-Chemical
+)	O
+,	O
+an	O
+inverse	O
+agonist	O
+of	O
+the	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+receptor	O
+benzodiazepine	B-Chemical
+site	O
+.	O
+
+Our	O
+aim	O
+was	O
+to	O
+characterize	O
+both	O
+lines	O
+'	O
+sensitivities	O
+to	O
+various	O
+physiological	O
+effects	O
+of	O
+other	O
+ligands	O
+of	O
+the	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+receptor	O
+.	O
+
+We	O
+measured	O
+diazepam	B-Chemical
+-	O
+induced	O
+anxiolysis	O
+with	O
+the	O
+elevated	O
+plus	O
+-	O
+maze	O
+test	O
+,	O
+diazepam	B-Chemical
+-	O
+induced	O
+sedation	O
+by	O
+recording	O
+the	O
+vigilance	O
+states	O
+,	O
+and	O
+picrotoxin	B-Chemical
+-	O
+and	O
+pentylenetetrazol	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+after	O
+i	O
+.	O
+p	O
+.	O
+injections	O
+.	O
+
+Results	O
+presented	O
+here	O
+show	O
+that	O
+the	O
+differential	O
+sensitivities	O
+of	O
+BS	O
+and	O
+BR	O
+lines	O
+to	O
+beta	B-Chemical
+-	I-Chemical
+CCM	I-Chemical
+can	O
+be	O
+extended	O
+to	O
+diazepam	B-Chemical
+,	O
+picrotoxin	B-Chemical
+,	O
+and	O
+pentylenetetrazol	B-Chemical
+,	O
+suggesting	O
+a	O
+genetic	O
+selection	O
+of	O
+a	O
+general	O
+sensitivity	O
+and	O
+resistance	O
+to	O
+several	O
+ligands	O
+of	O
+the	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+receptor	O
+.	O
+
+Propylthiouracil	B-Chemical
+-	O
+induced	O
+perinuclear	O
+-	O
+staining	O
+antineutrophil	O
+cytoplasmic	O
+autoantibody	O
+-	O
+positive	O
+vasculitis	B-Disease
+in	O
+conjunction	O
+with	O
+pericarditis	B-Disease
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+describe	O
+a	O
+case	O
+of	O
+propylthiouracil	B-Chemical
+-	O
+induced	O
+vasculitis	B-Disease
+manifesting	O
+with	O
+pericarditis	B-Disease
+.	O
+
+METHODS	O
+:	O
+We	O
+present	O
+the	O
+first	O
+case	O
+report	O
+of	O
+a	O
+woman	O
+with	O
+hyperthyroidism	B-Disease
+treated	O
+with	O
+propylthiouracil	B-Chemical
+in	O
+whom	O
+a	O
+syndrome	O
+of	O
+pericarditis	B-Disease
+,	O
+fever	B-Disease
+,	O
+and	O
+glomerulonephritis	B-Disease
+developed	O
+.	O
+
+Serologic	O
+testing	O
+and	O
+immunologic	O
+studies	O
+were	O
+done	O
+,	O
+and	O
+a	O
+pericardial	O
+biopsy	O
+was	O
+performed	O
+.	O
+
+RESULTS	O
+:	O
+A	O
+25	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+Graves	B-Disease
+'	I-Disease
+disease	I-Disease
+had	O
+a	O
+febrile	B-Disease
+illness	I-Disease
+and	O
+evidence	O
+of	O
+pericarditis	B-Disease
+,	O
+which	O
+was	O
+confirmed	O
+by	O
+biopsy	O
+.	O
+
+Serologic	O
+evaluation	O
+revealed	O
+the	O
+presence	O
+of	O
+perinuclear	O
+-	O
+staining	O
+antineutrophil	O
+cytoplasmic	O
+autoantibodies	O
+(	O
+pANCA	O
+)	O
+against	O
+myeloperoxidase	O
+(	O
+MPO	O
+)	O
+.	O
+
+Propylthiouracil	B-Chemical
+therapy	O
+was	O
+withdrawn	O
+,	O
+and	O
+she	O
+was	O
+treated	O
+with	O
+a	O
+1	O
+-	O
+month	O
+course	O
+of	O
+prednisone	B-Chemical
+,	O
+which	O
+alleviated	O
+her	O
+symptoms	O
+.	O
+
+A	O
+literature	O
+review	O
+revealed	O
+no	O
+prior	O
+reports	O
+of	O
+pericarditis	B-Disease
+in	O
+anti	O
+-	O
+MPO	O
+pANCA	O
+-	O
+positive	O
+vasculitis	B-Disease
+associated	O
+with	O
+propylthio	B-Chemical
+-	I-Chemical
+uracil	I-Chemical
+therapy	O
+.	O
+
+CONCLUSION	O
+:	O
+Pericarditis	B-Disease
+may	O
+be	O
+the	O
+initial	O
+manifestation	O
+of	O
+drug	O
+-	O
+induced	O
+vasculitis	B-Disease
+attributable	O
+to	O
+propylthio	B-Chemical
+-	I-Chemical
+uracil	I-Chemical
+therapy	O
+.	O
+
+Repeated	O
+transient	O
+anuria	B-Disease
+following	O
+losartan	B-Chemical
+administration	O
+in	O
+a	O
+patient	O
+with	O
+a	O
+solitary	O
+kidney	O
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+70	O
+-	O
+year	O
+-	O
+old	O
+hypertensive	B-Disease
+man	O
+with	O
+a	O
+solitary	O
+kidney	O
+and	O
+chronic	B-Disease
+renal	I-Disease
+insufficiency	I-Disease
+who	O
+developed	O
+two	O
+episodes	O
+of	O
+transient	O
+anuria	B-Disease
+after	O
+losartan	B-Chemical
+administration	O
+.	O
+
+He	O
+was	O
+hospitalized	O
+for	O
+a	O
+myocardial	B-Disease
+infarction	I-Disease
+with	O
+pulmonary	B-Disease
+edema	I-Disease
+,	O
+treated	O
+with	O
+high	O
+-	O
+dose	O
+diuretics	O
+.	O
+
+Due	O
+to	O
+severe	O
+systolic	B-Disease
+dysfunction	I-Disease
+losartan	B-Chemical
+was	O
+prescribed	O
+.	O
+
+Surprisingly	O
+,	O
+the	O
+first	O
+dose	O
+of	O
+50	O
+mg	O
+of	O
+losartan	B-Chemical
+resulted	O
+in	O
+a	O
+sudden	O
+anuria	B-Disease
+,	O
+which	O
+lasted	O
+eight	O
+hours	O
+despite	O
+high	O
+-	O
+dose	O
+furosemide	B-Chemical
+and	O
+amine	B-Chemical
+infusion	O
+.	O
+
+One	O
+week	O
+later	O
+,	O
+by	O
+mistake	O
+,	O
+losartan	B-Chemical
+was	O
+prescribed	O
+again	O
+and	O
+after	O
+the	O
+second	O
+dose	O
+of	O
+50	O
+mg	O
+,	O
+the	O
+patient	O
+developed	O
+a	O
+second	O
+episode	O
+of	O
+transient	O
+anuria	B-Disease
+lasting	O
+10	O
+hours	O
+.	O
+
+During	O
+these	O
+two	O
+episodes	O
+,	O
+his	O
+blood	O
+pressure	O
+diminished	O
+but	O
+no	O
+severe	O
+hypotension	B-Disease
+was	O
+noted	O
+.	O
+
+Ultimately	O
+,	O
+an	O
+arteriography	O
+showed	O
+a	O
+70	O
+-	O
+80	O
+%	O
+renal	B-Disease
+artery	I-Disease
+stenosis	I-Disease
+.	O
+
+In	O
+this	O
+patient	O
+,	O
+renal	B-Disease
+artery	I-Disease
+stenosis	I-Disease
+combined	O
+with	O
+heart	B-Disease
+failure	I-Disease
+and	O
+diuretic	O
+therapy	O
+certainly	O
+resulted	O
+in	O
+a	O
+strong	O
+activation	O
+of	O
+the	O
+renin	O
+-	O
+angiotensin	B-Chemical
+system	O
+(	O
+RAS	O
+)	O
+.	O
+
+Under	O
+such	O
+conditions	O
+,	O
+angiotensin	B-Chemical
+II	I-Chemical
+receptor	O
+blockade	O
+by	O
+losartan	B-Chemical
+probably	O
+induced	O
+a	O
+critical	O
+fall	O
+in	O
+glomerular	O
+filtration	O
+pressure	O
+.	O
+
+This	O
+case	O
+report	O
+highlights	O
+the	O
+fact	O
+that	O
+the	O
+angiotensin	B-Chemical
+II	I-Chemical
+receptor	O
+antagonist	O
+losartan	B-Chemical
+can	O
+cause	O
+serious	O
+unexpected	O
+complications	O
+in	O
+patients	O
+with	O
+renovascular	B-Disease
+disease	I-Disease
+and	O
+should	O
+be	O
+used	O
+with	O
+extreme	O
+caution	O
+in	O
+this	O
+setting	O
+.	O
+
+Calcineurin	O
+-	O
+inhibitor	O
+induced	O
+pain	B-Disease
+syndrome	O
+(	O
+CIPS	B-Disease
+)	O
+:	O
+a	O
+severe	O
+disabling	O
+complication	O
+after	O
+organ	O
+transplantation	O
+.	O
+
+Bone	O
+pain	B-Disease
+after	O
+transplantation	O
+is	O
+a	O
+frequent	O
+complication	O
+that	O
+can	O
+be	O
+caused	O
+by	O
+several	O
+diseases	O
+.	O
+
+Treatment	O
+strategies	O
+depend	O
+on	O
+the	O
+correct	O
+diagnosis	O
+of	O
+the	O
+pain	B-Disease
+.	O
+
+Nine	O
+patients	O
+with	O
+severe	O
+pain	B-Disease
+in	O
+their	O
+feet	O
+,	O
+which	O
+was	O
+registered	O
+after	O
+transplantation	O
+,	O
+were	O
+investigated	O
+.	O
+
+Bone	O
+scans	O
+showed	O
+an	O
+increased	O
+tracer	O
+uptake	O
+of	O
+the	O
+foot	O
+bones	O
+.	O
+
+Magnetic	O
+resonance	O
+imaging	O
+demonstrated	O
+bone	B-Disease
+marrow	I-Disease
+oedema	I-Disease
+in	O
+the	O
+painful	O
+bones	O
+.	O
+
+Pain	B-Disease
+was	O
+not	O
+explained	O
+by	O
+other	O
+diseases	O
+causing	O
+foot	O
+pain	B-Disease
+,	O
+like	O
+reflex	B-Disease
+sympathetic	I-Disease
+dystrophy	I-Disease
+,	O
+polyneuropathy	B-Disease
+,	O
+Morton	B-Disease
+'	I-Disease
+s	I-Disease
+neuralgia	I-Disease
+,	O
+gout	B-Disease
+,	O
+osteoporosis	B-Disease
+,	O
+avascular	B-Disease
+necrosis	I-Disease
+,	O
+intermittent	B-Disease
+claudication	I-Disease
+,	O
+orthopaedic	O
+foot	B-Disease
+deformities	I-Disease
+,	O
+stress	B-Disease
+fractures	I-Disease
+,	O
+and	O
+hyperparathyroidism	B-Disease
+.	O
+
+The	O
+reduction	O
+of	O
+cyclosporine	B-Chemical
+-	O
+or	O
+tacrolimus	B-Chemical
+trough	O
+levels	O
+and	O
+the	O
+administration	O
+of	O
+calcium	B-Chemical
+channel	O
+blockers	O
+led	O
+to	O
+relief	O
+of	O
+pain	B-Disease
+.	O
+
+The	O
+Calcineurin	O
+-	O
+inhibitor	O
+Induced	O
+Pain	B-Disease
+Syndrome	O
+(	O
+CIPS	B-Disease
+)	O
+is	O
+a	O
+rare	O
+but	O
+severe	O
+side	O
+effect	O
+of	O
+cyclosporine	B-Chemical
+or	O
+tacrolimus	B-Chemical
+and	O
+is	O
+accurately	O
+diagnosed	O
+by	O
+its	O
+typical	O
+presentation	O
+,	O
+magnetic	O
+resonance	O
+imaging	O
+and	O
+bone	O
+scans	O
+.	O
+
+Incorrect	O
+diagnosis	O
+of	O
+the	O
+syndrome	O
+will	O
+lead	O
+to	O
+a	O
+significant	O
+reduction	O
+of	O
+life	O
+quality	O
+in	O
+patients	O
+suffering	O
+from	O
+CIPS	B-Disease
+.	O
+
+Brain	O
+natriuretic	O
+peptide	O
+is	O
+a	O
+predictor	O
+of	O
+anthracycline	B-Chemical
+-	O
+induced	O
+cardiotoxicity	B-Disease
+.	O
+
+Anthracyclines	B-Chemical
+are	O
+effective	O
+antineoplastic	O
+drugs	O
+,	O
+but	O
+they	O
+frequently	O
+cause	O
+dose	O
+-	O
+related	O
+cardiotoxicity	B-Disease
+.	O
+
+The	O
+cardiotoxicity	B-Disease
+of	O
+conventional	O
+anthracycline	B-Chemical
+therapy	O
+highlights	O
+a	O
+need	O
+to	O
+search	O
+for	O
+methods	O
+that	O
+are	O
+highly	O
+sensitive	O
+and	O
+capable	O
+of	O
+predicting	O
+cardiac	B-Disease
+dysfunction	I-Disease
+.	O
+
+We	O
+measured	O
+the	O
+plasma	O
+level	O
+of	O
+brain	O
+natriuretic	O
+peptide	O
+(	O
+BNP	O
+)	O
+to	O
+determine	O
+whether	O
+BNP	O
+might	O
+serve	O
+as	O
+a	O
+simple	O
+diagnostic	O
+indicator	O
+of	O
+anthracycline	B-Chemical
+-	O
+induced	O
+cardiotoxicity	B-Disease
+in	O
+patients	O
+with	O
+acute	B-Disease
+leukemia	I-Disease
+treated	O
+with	O
+a	O
+daunorubicin	B-Chemical
+(	O
+DNR	B-Chemical
+)	O
+-	O
+containing	O
+regimen	O
+.	O
+
+Thirteen	O
+patients	O
+with	O
+acute	B-Disease
+leukemia	I-Disease
+were	O
+treated	O
+with	O
+a	O
+DNR	B-Chemical
+-	O
+containing	O
+regimen	O
+.	O
+
+Cardiac	O
+functions	O
+were	O
+evaluated	O
+with	O
+radionuclide	O
+angiography	O
+before	O
+chemotherapies	O
+.	O
+
+The	O
+plasma	O
+levels	O
+of	O
+atrial	O
+natriuretic	O
+peptide	O
+(	O
+ANP	O
+)	O
+and	O
+BNP	O
+were	O
+measured	O
+at	O
+the	O
+time	O
+of	O
+radionuclide	O
+angiography	O
+.	O
+
+Three	O
+patients	O
+developed	O
+congestive	B-Disease
+heart	I-Disease
+failure	I-Disease
+after	O
+the	O
+completion	O
+of	O
+chemotherapy	O
+.	O
+
+Five	O
+patients	O
+were	O
+diagnosed	O
+as	O
+having	O
+subclinical	O
+heart	B-Disease
+failure	I-Disease
+after	O
+the	O
+completion	O
+of	O
+chemotherapy	O
+.	O
+
+The	O
+plasma	O
+levels	O
+of	O
+BNP	O
+in	O
+all	O
+the	O
+patients	O
+with	O
+clinical	O
+and	O
+subclinical	O
+heart	B-Disease
+failure	I-Disease
+increased	O
+above	O
+the	O
+normal	O
+limit	O
+(	O
+40	O
+pg	O
+/	O
+ml	O
+)	O
+before	O
+the	O
+detection	O
+of	O
+clinical	O
+or	O
+subclinical	O
+heart	B-Disease
+failure	I-Disease
+by	O
+radionuclide	O
+angiography	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+BNP	O
+did	O
+not	O
+increase	O
+in	O
+the	O
+patients	O
+without	O
+heart	B-Disease
+failure	I-Disease
+given	O
+DNR	B-Chemical
+,	O
+even	O
+at	O
+more	O
+than	O
+700	O
+mg	O
+/	O
+m	O
+(	O
+2	O
+)	O
+.	O
+
+The	O
+plasma	O
+level	O
+of	O
+ANP	O
+did	O
+not	O
+always	O
+increase	O
+in	O
+all	O
+the	O
+patients	O
+with	O
+clinical	O
+and	O
+subclinical	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+These	O
+preliminary	O
+results	O
+suggest	O
+that	O
+BNP	O
+may	O
+be	O
+useful	O
+as	O
+an	O
+early	O
+and	O
+sensitive	O
+indicator	O
+of	O
+anthracycline	B-Chemical
+-	O
+induced	O
+cardiotoxicity	B-Disease
+.	O
+
+Nephrotoxicity	B-Disease
+of	O
+combined	O
+cephalothin	B-Chemical
+-	O
+gentamicin	B-Chemical
+regimen	O
+.	O
+
+Two	O
+patients	O
+developed	O
+acute	B-Disease
+tubular	I-Disease
+necrosis	I-Disease
+,	O
+characterized	O
+clinically	O
+by	O
+acute	O
+oliguric	B-Disease
+renal	I-Disease
+failure	I-Disease
+,	O
+while	O
+they	O
+were	O
+receiving	O
+a	O
+combination	O
+of	O
+cephalothin	B-Chemical
+sodium	I-Chemical
+and	O
+gentamicin	B-Chemical
+sulfate	I-Chemical
+therapy	O
+.	O
+
+Patients	O
+who	O
+are	O
+given	O
+this	O
+drug	O
+regimen	O
+should	O
+be	O
+observed	O
+very	O
+carefully	O
+for	O
+early	O
+signs	O
+of	O
+nephrotoxicity	B-Disease
+.	O
+
+High	O
+doses	O
+of	O
+this	O
+antibiotic	O
+combination	O
+should	O
+be	O
+avoided	O
+especially	O
+in	O
+elderly	O
+patients	O
+.	O
+
+Patients	O
+with	O
+renal	B-Disease
+insufficiency	I-Disease
+should	O
+not	O
+be	O
+given	O
+this	O
+regimen	O
+.	O
+
+In	O
+vivo	O
+protection	O
+of	O
+dna	O
+damage	O
+associated	O
+apoptotic	O
+and	O
+necrotic	B-Disease
+cell	O
+deaths	O
+during	O
+acetaminophen	B-Chemical
+-	O
+induced	O
+nephrotoxicity	B-Disease
+,	O
+amiodarone	B-Chemical
+-	O
+induced	O
+lung	B-Disease
+toxicity	I-Disease
+and	O
+doxorubicin	B-Chemical
+-	O
+induced	O
+cardiotoxicity	B-Disease
+by	O
+a	O
+novel	O
+IH636	B-Chemical
+grape	I-Chemical
+seed	I-Chemical
+proanthocyanidin	I-Chemical
+extract	I-Chemical
+.	O
+
+Grape	B-Chemical
+seed	I-Chemical
+extract	I-Chemical
+,	O
+primarily	O
+a	O
+mixture	O
+of	O
+proanthocyanidins	B-Chemical
+,	O
+has	O
+been	O
+shown	O
+to	O
+modulate	O
+a	O
+wide	O
+-	O
+range	O
+of	O
+biological	O
+,	O
+pharmacological	O
+and	O
+toxicological	O
+effects	O
+which	O
+are	O
+mainly	O
+cytoprotective	O
+.	O
+
+This	O
+study	O
+assessed	O
+the	O
+ability	O
+of	O
+IH636	B-Chemical
+grape	I-Chemical
+seed	I-Chemical
+proanthocyanidin	I-Chemical
+extract	I-Chemical
+(	O
+GSPE	B-Chemical
+)	O
+to	O
+prevent	O
+acetaminophen	B-Chemical
+(	O
+AAP	B-Chemical
+)	O
+-	O
+induced	O
+nephrotoxicity	B-Disease
+,	O
+amiodarone	B-Chemical
+(	O
+AMI	B-Chemical
+)	O
+-	O
+induced	O
+lung	B-Disease
+toxicity	I-Disease
+,	O
+and	O
+doxorubicin	B-Chemical
+(	O
+DOX	B-Chemical
+)	O
+-	O
+induced	O
+cardiotoxicity	B-Disease
+in	O
+mice	O
+.	O
+
+Experimental	O
+design	O
+consisted	O
+of	O
+four	O
+groups	O
+:	O
+control	O
+(	O
+vehicle	O
+alone	O
+)	O
+,	O
+GSPE	B-Chemical
+alone	O
+,	O
+drug	O
+alone	O
+and	O
+GSPE	B-Chemical
++	O
+drug	O
+.	O
+
+For	O
+the	O
+cytoprotection	O
+study	O
+,	O
+animals	O
+were	O
+orally	O
+gavaged	O
+100	O
+mg	O
+/	O
+Kg	O
+GSPE	B-Chemical
+for	O
+7	O
+-	O
+10	O
+days	O
+followed	O
+by	O
+i	O
+.	O
+p	O
+.	O
+injections	O
+of	O
+organ	O
+specific	O
+three	O
+drugs	O
+(	O
+AAP	B-Chemical
+:	O
+500	O
+mg	O
+/	O
+Kg	O
+for	O
+24	O
+h	O
+;	O
+AMI	B-Chemical
+:	O
+50	O
+mg	O
+/	O
+Kg	O
+/	O
+day	O
+for	O
+four	O
+days	O
+;	O
+DOX	B-Chemical
+:	O
+20	O
+mg	O
+/	O
+Kg	O
+for	O
+48	O
+h	O
+)	O
+.	O
+
+Parameters	O
+of	O
+study	O
+included	O
+analysis	O
+of	O
+serum	O
+chemistry	O
+(	O
+ALT	O
+,	O
+BUN	O
+and	O
+CPK	O
+)	O
+,	O
+and	O
+orderly	O
+fragmentation	O
+of	O
+genomic	O
+DNA	O
+(	O
+both	O
+endonuclease	O
+-	O
+dependent	O
+and	O
+independent	O
+)	O
+in	O
+addition	O
+to	O
+microscopic	O
+evaluation	O
+of	O
+damage	O
+and	O
+/	O
+or	O
+protection	O
+in	O
+corresponding	O
+PAS	O
+stained	O
+tissues	O
+.	O
+
+Results	O
+indicate	O
+that	O
+GSPE	B-Chemical
+preexposure	O
+prior	O
+to	O
+AAP	B-Chemical
+,	O
+AMI	B-Chemical
+and	O
+DOX	B-Chemical
+,	O
+provided	O
+near	O
+complete	O
+protection	O
+in	O
+terms	O
+of	O
+serum	O
+chemistry	O
+changes	O
+(	O
+ALT	O
+,	O
+BUN	O
+and	O
+CPK	O
+)	O
+,	O
+and	O
+significantly	O
+reduced	O
+DNA	O
+fragmentation	O
+.	O
+
+Histopathological	O
+examination	O
+of	O
+kidney	O
+,	O
+heart	O
+and	O
+lung	O
+sections	O
+revealed	O
+moderate	O
+to	O
+massive	O
+tissue	B-Disease
+damage	I-Disease
+with	O
+a	O
+variety	O
+of	O
+morphological	O
+aberrations	O
+by	O
+all	O
+the	O
+three	O
+drugs	O
+in	O
+the	O
+absence	O
+of	O
+GSPE	B-Chemical
+preexposure	O
+than	O
+in	O
+its	O
+presence	O
+.	O
+
+GSPE	B-Chemical
++	O
+drug	O
+exposed	O
+tissues	O
+exhibited	O
+minor	O
+residual	O
+damage	O
+or	O
+near	O
+total	O
+recovery	O
+.	O
+
+Additionally	O
+,	O
+histopathological	O
+alterations	O
+mirrored	O
+both	O
+serum	O
+chemistry	O
+changes	O
+and	O
+the	O
+pattern	O
+of	O
+DNA	O
+fragmentation	O
+.	O
+
+Interestingly	O
+,	O
+all	O
+the	O
+drugs	O
+,	O
+such	O
+as	O
+,	O
+AAP	B-Chemical
+,	O
+AMI	B-Chemical
+and	O
+DOX	B-Chemical
+induced	O
+apoptotic	O
+death	O
+in	O
+addition	O
+to	O
+necrosis	B-Disease
+in	O
+the	O
+respective	O
+organs	O
+which	O
+was	O
+very	O
+effectively	O
+blocked	O
+by	O
+GSPE	B-Chemical
+.	O
+
+Since	O
+AAP	B-Chemical
+,	O
+AMI	B-Chemical
+and	O
+DOX	B-Chemical
+undergo	O
+biotransformation	O
+and	O
+are	O
+known	O
+to	O
+produce	O
+damaging	O
+radicals	O
+in	O
+vivo	O
+,	O
+the	O
+protection	O
+by	O
+GSPE	B-Chemical
+may	O
+be	O
+linked	O
+to	O
+both	O
+inhibition	O
+of	O
+metabolism	O
+and	O
+/	O
+or	O
+detoxification	O
+of	O
+cytotoxic	O
+radicals	O
+.	O
+
+In	O
+addition	O
+,	O
+its	O
+'	O
+presumed	O
+contribution	O
+to	O
+DNA	O
+repair	O
+may	O
+be	O
+another	O
+important	O
+attribute	O
+,	O
+which	O
+played	O
+a	O
+role	O
+in	O
+the	O
+chemoprevention	O
+process	O
+.	O
+
+Additionally	O
+,	O
+this	O
+may	O
+have	O
+been	O
+the	O
+first	O
+report	O
+on	O
+AMI	B-Chemical
+-	O
+induced	O
+apoptotic	O
+death	O
+in	O
+the	O
+lung	O
+tissue	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+events	O
+undoubtedly	O
+establish	O
+GSPE	B-Chemical
+'	O
+s	O
+abundant	O
+bioavailability	O
+,	O
+and	O
+the	O
+power	O
+to	O
+defend	O
+multiple	O
+target	O
+organs	O
+from	O
+toxic	O
+assaults	O
+induced	O
+by	O
+structurally	O
+diverse	O
+and	O
+functionally	O
+different	O
+entities	O
+in	O
+vivo	O
+.	O
+
+Antidepressant	B-Chemical
+-	O
+induced	O
+mania	B-Disease
+in	O
+bipolar	B-Disease
+patients	O
+:	O
+identification	O
+of	O
+risk	O
+factors	O
+.	O
+
+BACKGROUND	O
+:	O
+Concerns	O
+about	O
+possible	O
+risks	O
+of	O
+switching	O
+to	O
+mania	B-Disease
+associated	O
+with	O
+antidepressants	B-Chemical
+continue	O
+to	O
+interfere	O
+with	O
+the	O
+establishment	O
+of	O
+an	O
+optimal	O
+treatment	O
+paradigm	O
+for	O
+bipolar	B-Disease
+depression	I-Disease
+.	O
+
+METHOD	O
+:	O
+The	O
+response	O
+of	O
+44	O
+patients	O
+meeting	O
+DSM	O
+-	O
+IV	O
+criteria	O
+for	O
+bipolar	B-Disease
+disorder	I-Disease
+to	O
+naturalistic	O
+treatment	O
+was	O
+assessed	O
+for	O
+at	O
+least	O
+6	O
+weeks	O
+using	O
+the	O
+Montgomery	O
+-	O
+Asberg	O
+Depression	O
+Rating	O
+Scale	O
+and	O
+the	O
+Bech	O
+-	O
+Rafaelson	O
+Mania	O
+Rating	O
+Scale	O
+.	O
+
+Patients	O
+who	O
+experienced	O
+a	O
+manic	B-Disease
+or	O
+hypomanic	B-Disease
+switch	O
+were	O
+compared	O
+with	O
+those	O
+who	O
+did	O
+not	O
+on	O
+several	O
+variables	O
+including	O
+age	O
+,	O
+sex	O
+,	O
+diagnosis	O
+(	O
+DSM	B-Disease
+-	I-Disease
+IV	I-Disease
+bipolar	I-Disease
+I	I-Disease
+vs	O
+.	O
+bipolar	B-Disease
+II	I-Disease
+)	O
+,	O
+number	O
+of	O
+previous	O
+manic	B-Disease
+episodes	O
+,	O
+type	O
+of	O
+antidepressant	B-Chemical
+therapy	O
+used	O
+(	O
+electroconvulsive	O
+therapy	O
+vs	O
+.	O
+antidepressant	B-Chemical
+drugs	O
+and	O
+,	O
+more	O
+particularly	O
+,	O
+selective	O
+serotonin	B-Chemical
+reuptake	I-Chemical
+inhibitors	I-Chemical
+[	O
+SSRIs	B-Chemical
+]	O
+)	O
+,	O
+use	O
+and	O
+type	O
+of	O
+mood	O
+stabilizers	O
+(	O
+lithium	B-Chemical
+vs	O
+.	O
+anticonvulsants	O
+)	O
+,	O
+and	O
+temperament	O
+of	O
+the	O
+patient	O
+,	O
+assessed	O
+during	O
+a	O
+normothymic	O
+period	O
+using	O
+the	O
+hyperthymia	O
+component	O
+of	O
+the	O
+Semi	O
+-	O
+structured	O
+Affective	O
+Temperament	O
+Interview	O
+.	O
+
+RESULTS	O
+:	O
+Switches	O
+to	O
+hypomania	B-Disease
+or	O
+mania	B-Disease
+occurred	O
+in	O
+27	O
+%	O
+of	O
+all	O
+patients	O
+(	O
+N	O
+=	O
+12	O
+)	O
+(	O
+and	O
+in	O
+24	O
+%	O
+of	O
+the	O
+subgroup	O
+of	O
+patients	O
+treated	O
+with	O
+SSRIs	B-Chemical
+[	O
+8	O
+/	O
+33	O
+]	O
+)	O
+;	O
+16	O
+%	O
+(	O
+N	O
+=	O
+7	O
+)	O
+experienced	O
+manic	B-Disease
+episodes	O
+,	O
+and	O
+11	O
+%	O
+(	O
+N	O
+=	O
+5	O
+)	O
+experienced	O
+hypomanic	B-Disease
+episodes	O
+.	O
+
+Sex	O
+,	O
+age	O
+,	O
+diagnosis	O
+(	O
+bipolar	B-Disease
+I	I-Disease
+vs	O
+.	O
+bipolar	B-Disease
+II	I-Disease
+)	O
+,	O
+and	O
+additional	O
+treatment	O
+did	O
+not	O
+affect	O
+the	O
+risk	O
+of	O
+switching	O
+.	O
+
+The	O
+incidence	O
+of	O
+mood	O
+switches	O
+seemed	O
+not	O
+to	O
+differ	O
+between	O
+patients	O
+receiving	O
+an	O
+anticonvulsant	O
+and	O
+those	O
+receiving	O
+no	O
+mood	O
+stabilizer	O
+.	O
+
+In	O
+contrast	O
+,	O
+mood	O
+switches	O
+were	O
+less	O
+frequent	O
+in	O
+patients	O
+receiving	O
+lithium	B-Chemical
+(	O
+15	O
+%	O
+,	O
+4	O
+/	O
+26	O
+)	O
+than	O
+in	O
+patients	O
+not	O
+treated	O
+with	O
+lithium	B-Chemical
+(	O
+44	O
+%	O
+,	O
+8	O
+/	O
+18	O
+;	O
+p	O
+=	O
+.	O
+04	O
+)	O
+.	O
+
+The	O
+number	O
+of	O
+previous	O
+manic	B-Disease
+episodes	O
+did	O
+not	O
+affect	O
+the	O
+probability	O
+of	O
+switching	O
+,	O
+whereas	O
+a	O
+high	O
+score	O
+on	O
+the	O
+hyperthymia	O
+component	O
+of	O
+the	O
+Semistructured	O
+Affective	O
+Temperament	O
+Interview	O
+was	O
+associated	O
+with	O
+a	O
+greater	O
+risk	O
+of	O
+switching	O
+(	O
+p	O
+=	O
+.	O
+008	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+frequency	O
+of	O
+mood	O
+switching	O
+associated	O
+with	O
+acute	O
+antidepressant	B-Chemical
+therapy	O
+may	O
+be	O
+reduced	O
+by	O
+lithium	B-Chemical
+treatment	O
+.	O
+
+Particular	O
+attention	O
+should	O
+be	O
+paid	O
+to	O
+patients	O
+with	O
+a	O
+hyperthymic	O
+temperament	O
+,	O
+who	O
+have	O
+a	O
+greater	O
+risk	O
+of	O
+mood	O
+switches	O
+.	O
+
+Peritubular	O
+capillary	O
+basement	O
+membrane	O
+reduplication	O
+in	O
+allografts	O
+and	O
+native	O
+kidney	B-Disease
+disease	I-Disease
+:	O
+a	O
+clinicopathologic	O
+study	O
+of	O
+278	O
+consecutive	O
+renal	O
+specimens	O
+.	O
+
+BACKGROUND	O
+:	O
+An	O
+association	O
+has	O
+been	O
+found	O
+between	O
+transplant	B-Disease
+glomerulopathy	I-Disease
+(	O
+TG	B-Disease
+)	O
+and	O
+reduplication	O
+of	O
+peritubular	O
+capillary	O
+basement	O
+membranes	O
+(	O
+PTCR	O
+)	O
+.	O
+
+Although	O
+such	O
+an	O
+association	O
+is	O
+of	O
+practical	O
+and	O
+theoretical	O
+importance	O
+,	O
+only	O
+one	O
+prospective	O
+study	O
+has	O
+tried	O
+to	O
+confirm	O
+it	O
+.	O
+
+METHODS	O
+:	O
+We	O
+examined	O
+278	O
+consecutive	O
+renal	O
+specimens	O
+(	O
+from	O
+135	O
+transplants	O
+and	O
+143	O
+native	O
+kidneys	O
+)	O
+for	O
+ultrastructural	O
+evidence	O
+of	O
+PTCR	O
+.	O
+
+In	O
+addition	O
+to	O
+renal	O
+allografts	O
+with	O
+TG	B-Disease
+,	O
+we	O
+also	O
+examined	O
+grafts	O
+with	O
+acute	O
+rejection	O
+,	O
+recurrent	O
+glomerulonephritis	B-Disease
+,	O
+chronic	B-Disease
+allograft	I-Disease
+nephropathy	I-Disease
+and	O
+stable	O
+grafts	O
+(	O
+"	O
+protocol	O
+biopsies	O
+"	O
+)	O
+.	O
+
+Native	O
+kidney	O
+specimens	O
+included	O
+a	O
+wide	O
+range	O
+of	O
+glomerulopathies	B-Disease
+as	O
+well	O
+as	O
+cases	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+,	O
+malignant	B-Disease
+hypertension	I-Disease
+,	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+,	O
+and	O
+acute	B-Disease
+tubular	I-Disease
+necrosis	I-Disease
+.	O
+
+RESULTS	O
+:	O
+We	O
+found	O
+PTCR	O
+in	O
+14	O
+of	O
+15	O
+cases	O
+of	O
+TG	B-Disease
+,	O
+in	O
+7	O
+transplant	O
+biopsy	O
+specimens	O
+without	O
+TG	B-Disease
+,	O
+and	O
+in	O
+13	O
+of	O
+143	O
+native	O
+kidney	O
+biopsy	O
+specimens	O
+.	O
+
+These	O
+13	O
+included	O
+cases	O
+of	O
+malignant	B-Disease
+hypertension	I-Disease
+,	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+,	O
+lupus	B-Disease
+nephritis	I-Disease
+,	O
+Henoch	B-Disease
+-	I-Disease
+Schonlein	I-Disease
+nephritis	I-Disease
+,	O
+crescentic	O
+glomerulonephritis	B-Disease
+,	O
+and	O
+cocaine	B-Chemical
+-	O
+related	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+.	O
+
+Mild	O
+PTCR	O
+in	O
+allografts	O
+without	O
+TG	B-Disease
+did	O
+not	O
+predict	O
+renal	B-Disease
+failure	I-Disease
+or	O
+significant	O
+proteinuria	B-Disease
+after	O
+follow	O
+-	O
+up	O
+periods	O
+of	O
+between	O
+3	O
+months	O
+and	O
+1	O
+year	O
+.	O
+
+CONCLUSIONS	O
+:	O
+We	O
+conclude	O
+that	O
+in	O
+transplants	O
+,	O
+there	O
+is	O
+a	O
+strong	O
+association	O
+between	O
+well	O
+-	O
+developed	O
+PTCR	O
+and	O
+TG	B-Disease
+,	O
+while	O
+the	O
+significance	O
+of	O
+mild	O
+PTCR	O
+and	O
+its	O
+predictive	O
+value	O
+in	O
+the	O
+absence	O
+of	O
+TG	B-Disease
+is	O
+unclear	O
+.	O
+
+PTCR	O
+also	O
+occurs	O
+in	O
+certain	O
+native	O
+kidney	B-Disease
+diseases	I-Disease
+,	O
+though	O
+the	O
+association	O
+is	O
+not	O
+as	O
+strong	O
+as	O
+that	O
+for	O
+TG	B-Disease
+.	O
+
+We	O
+suggest	O
+that	O
+repeated	O
+endothelial	B-Disease
+injury	I-Disease
+,	O
+including	O
+immunologic	B-Disease
+injury	I-Disease
+,	O
+may	O
+be	O
+the	O
+cause	O
+of	O
+this	O
+lesion	O
+both	O
+in	O
+allografts	O
+and	O
+native	O
+kidneys	O
+.	O
+
+Caffeine	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+arrhythmia	I-Disease
+:	O
+an	O
+unrecognised	O
+danger	O
+of	O
+healthfood	O
+products	O
+.	O
+
+We	O
+describe	O
+a	O
+25	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+pre	O
+-	O
+existing	O
+mitral	B-Disease
+valve	I-Disease
+prolapse	I-Disease
+who	O
+developed	O
+intractable	O
+ventricular	B-Disease
+fibrillation	I-Disease
+after	O
+consuming	O
+a	O
+"	O
+natural	O
+energy	O
+"	O
+guarana	O
+health	O
+drink	O
+containing	O
+a	O
+high	O
+concentration	O
+of	O
+caffeine	B-Chemical
+.	O
+
+This	O
+case	O
+highlights	O
+the	O
+need	O
+for	O
+adequate	O
+labelling	O
+and	O
+regulation	O
+of	O
+such	O
+products	O
+.	O
+
+Conformationally	O
+restricted	O
+analogs	O
+of	O
+BD1008	B-Chemical
+and	O
+an	O
+antisense	O
+oligodeoxynucleotide	B-Chemical
+targeting	O
+sigma1	O
+receptors	O
+produce	O
+anti	O
+-	O
+cocaine	B-Chemical
+effects	O
+in	O
+mice	O
+.	O
+
+Cocaine	B-Chemical
+'	O
+s	O
+ability	O
+to	O
+interact	O
+with	O
+sigma	O
+receptors	O
+suggests	O
+that	O
+these	O
+proteins	O
+mediate	O
+some	O
+of	O
+its	O
+behavioral	O
+effects	O
+.	O
+
+Therefore	O
+,	O
+three	O
+novel	O
+sigma	O
+receptor	O
+ligands	O
+with	O
+antagonist	O
+activity	O
+were	O
+evaluated	O
+in	O
+Swiss	O
+Webster	O
+mice	O
+:	O
+BD1018	B-Chemical
+(	O
+3S	B-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+[	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+3	I-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dichlorophenyl	I-Chemical
+)	I-Chemical
+ethyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+1	I-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+diazabicyclo	I-Chemical
+[	I-Chemical
+4	I-Chemical
+.	I-Chemical
+3	I-Chemical
+.	I-Chemical
+0	I-Chemical
+]	I-Chemical
+nonane	I-Chemical
+)	O
+,	O
+BD1063	B-Chemical
+(	O
+1	B-Chemical
+-	I-Chemical
+[	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+3	I-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dichlorophenyl	I-Chemical
+)	I-Chemical
+ethyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+methylpiperazine	I-Chemical
+)	O
+,	O
+and	O
+LR132	B-Chemical
+(	O
+1R	O
+,	O
+2S	O
+-	O
+(	O
++	O
+)	O
+-	O
+cis	O
+-	O
+N	O
+-	O
+[	O
+2	O
+-	O
+(	O
+3	O
+,	O
+4	O
+-	O
+dichlorophenyl	O
+)	O
+ethyl	O
+]	O
+-	O
+2	O
+-	O
+(	O
+1	O
+-	O
+pyrrolidinyl	O
+)	O
+cyclohexylamine	O
+)	O
+.	O
+
+Competition	O
+binding	O
+assays	O
+demonstrated	O
+that	O
+all	O
+three	O
+compounds	O
+have	O
+high	O
+affinities	O
+for	O
+sigma1	O
+receptors	O
+.	O
+
+The	O
+three	O
+compounds	O
+vary	O
+in	O
+their	O
+affinities	O
+for	O
+sigma2	O
+receptors	O
+and	O
+exhibit	O
+negligible	O
+affinities	O
+for	O
+dopamine	B-Chemical
+,	O
+opioid	O
+,	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+and	O
+NMDA	B-Chemical
+receptors	O
+.	O
+
+In	O
+behavioral	O
+studies	O
+,	O
+pre	O
+-	O
+treatment	O
+of	O
+mice	O
+with	O
+BD1018	B-Chemical
+,	O
+BD1063	B-Chemical
+,	O
+or	O
+LR132	B-Chemical
+significantly	O
+attenuated	O
+cocaine	B-Chemical
+-	O
+induced	O
+convulsions	B-Disease
+and	O
+lethality	O
+.	O
+
+Moreover	O
+,	O
+post	O
+-	O
+treatment	O
+with	O
+LR132	B-Chemical
+prevented	O
+cocaine	B-Chemical
+-	O
+induced	O
+lethality	O
+in	O
+a	O
+significant	O
+proportion	O
+of	O
+animals	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+protection	O
+provided	O
+by	O
+the	O
+putative	O
+antagonists	O
+,	O
+the	O
+well	O
+-	O
+characterized	O
+sigma	O
+receptor	O
+agonist	O
+di	B-Chemical
+-	I-Chemical
+o	I-Chemical
+-	I-Chemical
+tolylguanidine	I-Chemical
+(	O
+DTG	B-Chemical
+)	O
+and	O
+the	O
+novel	O
+sigma	O
+receptor	O
+agonist	O
+BD1031	B-Chemical
+(	O
+3R	B-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+[	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+3	I-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dichlorophenyl	I-Chemical
+)	I-Chemical
+ethyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+1	I-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+diazabicyclo	I-Chemical
+[	I-Chemical
+4	I-Chemical
+.	I-Chemical
+3	I-Chemical
+.	I-Chemical
+0	I-Chemical
+]	I-Chemical
+nonane	I-Chemical
+)	O
+each	O
+worsened	O
+the	O
+behavioral	O
+toxicity	B-Disease
+of	O
+cocaine	B-Chemical
+.	O
+
+At	O
+doses	O
+where	O
+alone	O
+,	O
+they	O
+produced	O
+no	O
+significant	O
+effects	O
+on	O
+locomotion	O
+,	O
+BD1018	B-Chemical
+,	O
+BD1063	B-Chemical
+and	O
+LR132	B-Chemical
+significantly	O
+attenuated	O
+the	O
+locomotor	O
+stimulatory	O
+effects	O
+of	O
+cocaine	B-Chemical
+.	O
+
+To	O
+further	O
+validate	O
+the	O
+hypothesis	O
+that	O
+the	O
+anti	O
+-	O
+cocaine	B-Chemical
+effects	O
+of	O
+the	O
+novel	O
+ligands	O
+involved	O
+antagonism	O
+of	O
+sigma	O
+receptors	O
+,	O
+an	O
+antisense	O
+oligodeoxynucleotide	B-Chemical
+against	O
+sigma1	O
+receptors	O
+was	O
+also	O
+shown	O
+to	O
+significantly	O
+attenuate	O
+the	O
+convulsive	B-Disease
+and	O
+locomotor	O
+stimulatory	O
+effects	O
+of	O
+cocaine	B-Chemical
+.	O
+
+Together	O
+,	O
+the	O
+data	O
+suggests	O
+that	O
+functional	O
+antagonism	O
+of	O
+sigma	O
+receptors	O
+is	O
+capable	O
+of	O
+attenuating	O
+a	O
+number	O
+of	O
+cocaine	B-Chemical
+-	O
+induced	O
+behaviors	O
+.	O
+
+Ranitidine	B-Chemical
+-	O
+induced	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+in	O
+a	O
+cadaveric	O
+renal	O
+allograft	O
+.	O
+
+Ranitidine	B-Chemical
+frequently	O
+is	O
+used	O
+for	O
+preventing	O
+peptic	O
+ulceration	O
+after	O
+renal	O
+transplantation	O
+.	O
+
+This	O
+drug	O
+occasionally	O
+has	O
+been	O
+associated	O
+with	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+in	O
+native	O
+kidneys	O
+.	O
+
+There	O
+are	O
+no	O
+similar	O
+reports	O
+with	O
+renal	O
+transplantation	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+ranitidine	B-Chemical
+-	O
+induced	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+in	O
+a	O
+recipient	O
+of	O
+a	O
+cadaveric	O
+renal	O
+allograft	O
+presenting	O
+with	O
+acute	O
+allograft	O
+dysfunction	O
+within	O
+48	O
+hours	O
+of	O
+exposure	O
+to	O
+the	O
+drug	O
+.	O
+
+The	O
+biopsy	O
+specimen	O
+showed	O
+pathognomonic	O
+features	O
+,	O
+including	O
+eosinophilic	O
+infiltration	O
+of	O
+the	O
+interstitial	O
+compartment	O
+.	O
+
+Allograft	O
+function	O
+improved	O
+rapidly	O
+and	O
+returned	O
+to	O
+baseline	O
+after	O
+stopping	O
+the	O
+drug	O
+.	O
+
+Liver	B-Disease
+disease	I-Disease
+caused	O
+by	O
+propylthiouracil	B-Chemical
+.	O
+
+This	O
+report	O
+presents	O
+the	O
+clinical	O
+,	O
+laboratory	O
+,	O
+and	O
+light	O
+and	O
+electron	O
+microscopic	O
+observations	O
+on	O
+a	O
+patient	O
+with	O
+chronic	B-Disease
+active	I-Disease
+(	I-Disease
+aggressive	I-Disease
+)	I-Disease
+hepatitis	I-Disease
+caused	O
+by	O
+the	O
+administration	O
+of	O
+propylthiouracil	B-Chemical
+.	O
+
+This	O
+is	O
+an	O
+addition	O
+to	O
+the	O
+list	O
+of	O
+drugs	O
+that	O
+must	O
+be	O
+considered	O
+in	O
+the	O
+evaluation	O
+of	O
+chronic	O
+liver	B-Disease
+disease	I-Disease
+.	O
+
+Withdrawal	B-Disease
+-	I-Disease
+emergent	I-Disease
+rabbit	I-Disease
+syndrome	I-Disease
+during	O
+dose	O
+reduction	O
+of	O
+risperidone	B-Chemical
+.	O
+
+Rabbit	B-Disease
+syndrome	I-Disease
+(	O
+RS	B-Disease
+)	O
+is	O
+a	O
+rare	O
+extrapyramidal	O
+side	O
+effect	O
+caused	O
+by	O
+prolonged	O
+neuroleptic	O
+medication	O
+.	O
+
+Here	O
+we	O
+present	O
+a	O
+case	O
+of	O
+withdrawal	B-Disease
+-	I-Disease
+emergent	I-Disease
+RS	I-Disease
+,	O
+which	O
+is	O
+the	O
+first	O
+of	O
+its	O
+kind	O
+to	O
+be	O
+reported	O
+.	O
+
+The	O
+patient	O
+developed	O
+RS	B-Disease
+during	O
+dose	O
+reduction	O
+of	O
+risperidone	B-Chemical
+.	O
+
+The	O
+symptom	O
+was	O
+treated	O
+successfully	O
+with	O
+trihexyphenidyl	B-Chemical
+anticholinergic	O
+therapy	O
+.	O
+
+The	O
+underlying	O
+mechanism	O
+of	O
+withdrawal	B-Disease
+-	I-Disease
+emergent	I-Disease
+RS	I-Disease
+in	O
+the	O
+present	O
+case	O
+may	O
+have	O
+been	O
+related	O
+to	O
+the	O
+pharmacological	O
+profile	O
+of	O
+risperidone	B-Chemical
+,	O
+a	O
+serotonin	B-Chemical
+-	O
+dopamine	B-Chemical
+antagonist	O
+,	O
+suggesting	O
+the	O
+pathophysiologic	O
+influence	O
+of	O
+the	O
+serotonin	B-Chemical
+system	O
+in	O
+the	O
+development	O
+of	O
+RS	B-Disease
+.	O
+
+Pharmacokinetic	O
+/	O
+pharmacodynamic	O
+assessment	O
+of	O
+the	O
+effects	O
+of	O
+E4031	B-Chemical
+,	O
+cisapride	B-Chemical
+,	O
+terfenadine	B-Chemical
+and	O
+terodiline	B-Chemical
+on	O
+monophasic	O
+action	O
+potential	O
+duration	O
+in	O
+dog	O
+.	O
+
+1	O
+.	O
+
+Torsades	B-Disease
+de	I-Disease
+pointes	I-Disease
+(	O
+TDP	B-Disease
+)	O
+is	O
+a	O
+potentially	O
+fatal	O
+ventricular	B-Disease
+tachycardia	I-Disease
+associated	O
+with	O
+increases	O
+in	O
+QT	O
+interval	O
+and	O
+monophasic	O
+action	O
+potential	O
+duration	O
+(	O
+MAPD	O
+)	O
+.	O
+
+TDP	B-Disease
+is	O
+a	O
+side	O
+-	O
+effect	O
+that	O
+has	O
+led	O
+to	O
+withdrawal	O
+of	O
+several	O
+drugs	O
+from	O
+the	O
+market	O
+(	O
+e	O
+.	O
+g	O
+.	O
+terfenadine	B-Chemical
+and	O
+terodiline	B-Chemical
+)	O
+.	O
+
+2	O
+.	O
+
+The	O
+potential	O
+of	O
+compounds	O
+to	O
+cause	O
+TDP	B-Disease
+was	O
+evaluated	O
+by	O
+monitoring	O
+their	O
+effects	O
+on	O
+MAPD	O
+in	O
+dog	O
+.	O
+
+Four	O
+compounds	O
+known	O
+to	O
+increase	O
+QT	O
+interval	O
+and	O
+cause	O
+TDP	B-Disease
+were	O
+investigated	O
+:	O
+terfenadine	B-Chemical
+,	O
+terodiline	B-Chemical
+,	O
+cisapride	B-Chemical
+and	O
+E4031	B-Chemical
+.	O
+
+On	O
+the	O
+basis	O
+that	O
+only	O
+free	O
+drug	O
+in	O
+the	O
+systemic	O
+circulation	O
+will	O
+elicit	O
+a	O
+pharmacological	O
+response	O
+target	O
+,	O
+free	O
+concentrations	O
+in	O
+plasma	O
+were	O
+selected	O
+to	O
+mimic	O
+the	O
+free	O
+drug	O
+exposures	O
+in	O
+man	O
+.	O
+
+Infusion	O
+regimens	O
+were	O
+designed	O
+that	O
+rapidly	O
+achieved	O
+and	O
+maintained	O
+target	O
+-	O
+free	O
+concentrations	O
+of	O
+these	O
+drugs	O
+in	O
+plasma	O
+and	O
+data	O
+on	O
+the	O
+relationship	O
+between	O
+free	O
+concentration	O
+and	O
+changes	O
+in	O
+MAPD	O
+were	O
+obtained	O
+for	O
+these	O
+compounds	O
+.	O
+
+3	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+free	O
+ED50	O
+in	O
+plasma	O
+for	O
+terfenadine	B-Chemical
+(	O
+1	O
+.	O
+9	O
+nM	O
+)	O
+,	O
+terodiline	B-Chemical
+(	O
+76	O
+nM	O
+)	O
+,	O
+cisapride	B-Chemical
+(	O
+11	O
+nM	O
+)	O
+and	O
+E4031	B-Chemical
+(	O
+1	O
+.	O
+9	O
+nM	O
+)	O
+closely	O
+correlate	O
+with	O
+the	O
+free	O
+concentration	O
+in	O
+man	O
+causing	O
+QT	O
+effects	O
+.	O
+
+For	O
+compounds	O
+that	O
+have	O
+shown	O
+TDP	B-Disease
+in	O
+the	O
+clinic	O
+(	O
+terfenadine	B-Chemical
+,	O
+terodiline	B-Chemical
+,	O
+cisapride	B-Chemical
+)	O
+there	O
+is	O
+little	O
+differentiation	O
+between	O
+the	O
+dog	O
+ED50	O
+and	O
+the	O
+efficacious	O
+free	O
+plasma	O
+concentrations	O
+in	O
+man	O
+(	O
+<	O
+10	O
+-	O
+fold	O
+)	O
+reflecting	O
+their	O
+limited	O
+safety	O
+margins	O
+.	O
+
+These	O
+data	O
+underline	O
+the	O
+need	O
+to	O
+maximize	O
+the	O
+therapeutic	O
+ratio	O
+with	O
+respect	O
+to	O
+TDP	B-Disease
+in	O
+potential	O
+development	O
+candidates	O
+and	O
+the	O
+importance	O
+of	O
+using	O
+free	O
+drug	O
+concentrations	O
+in	O
+pharmacokinetic	O
+/	O
+pharmacodynamic	O
+studies	O
+.	O
+
+Bladder	O
+retention	B-Disease
+of	I-Disease
+urine	I-Disease
+as	O
+a	O
+result	O
+of	O
+continuous	O
+intravenous	O
+infusion	O
+of	O
+fentanyl	B-Chemical
+:	O
+2	O
+case	O
+reports	O
+.	O
+
+Sedation	O
+has	O
+been	O
+commonly	O
+used	O
+in	O
+the	O
+neonate	O
+to	O
+decrease	O
+the	O
+stress	O
+and	O
+pain	B-Disease
+from	O
+the	O
+noxious	O
+stimuli	O
+and	O
+invasive	O
+procedures	O
+in	O
+the	O
+neonatal	O
+intensive	O
+care	O
+unit	O
+,	O
+as	O
+well	O
+as	O
+to	O
+facilitate	O
+synchrony	O
+between	O
+ventilator	O
+and	O
+spontaneous	O
+breaths	O
+.	O
+
+Fentanyl	B-Chemical
+,	O
+an	O
+opioid	O
+analgesic	O
+,	O
+is	O
+frequently	O
+used	O
+in	O
+the	O
+neonatal	O
+intensive	O
+care	O
+unit	O
+setting	O
+for	O
+these	O
+very	O
+purposes	O
+.	O
+
+Various	O
+reported	O
+side	O
+effects	O
+of	O
+fentanyl	B-Chemical
+administration	O
+include	O
+chest	B-Disease
+wall	I-Disease
+rigidity	I-Disease
+,	O
+hypotension	B-Disease
+,	O
+respiratory	B-Disease
+depression	I-Disease
+,	O
+and	O
+bradycardia	B-Disease
+.	O
+
+Here	O
+,	O
+2	O
+cases	O
+of	O
+urinary	B-Disease
+bladder	I-Disease
+retention	I-Disease
+leading	O
+to	O
+renal	O
+pelvocalyceal	O
+dilatation	O
+mimicking	O
+hydronephrosis	B-Disease
+as	O
+a	O
+result	O
+of	O
+continuous	O
+infusion	O
+of	O
+fentanyl	B-Chemical
+are	O
+reported	O
+.	O
+
+Fatal	O
+myeloencephalopathy	B-Disease
+due	O
+to	O
+accidental	O
+intrathecal	O
+vincristin	B-Chemical
+administration	O
+:	O
+a	O
+report	O
+of	O
+two	O
+cases	O
+.	O
+
+We	O
+report	O
+on	O
+two	O
+fatal	O
+cases	O
+of	O
+accidental	O
+intrathecal	O
+vincristine	B-Chemical
+instillation	O
+in	O
+a	O
+5	O
+-	O
+year	O
+old	O
+girl	O
+with	O
+recurrent	O
+acute	B-Disease
+lymphoblastic	I-Disease
+leucemia	I-Disease
+and	O
+a	O
+57	O
+-	O
+year	O
+old	O
+man	O
+with	O
+lymphoblastic	B-Disease
+lymphoma	I-Disease
+.	O
+
+The	O
+girl	O
+died	O
+seven	O
+days	O
+,	O
+the	O
+man	O
+four	O
+weeks	O
+after	O
+intrathecal	O
+injection	O
+of	O
+vincristine	B-Chemical
+.	O
+
+Clinically	O
+,	O
+the	O
+onset	O
+was	O
+characterized	O
+by	O
+the	O
+signs	O
+of	O
+opistothonus	B-Disease
+,	I-Disease
+sensory	I-Disease
+and	I-Disease
+motor	I-Disease
+dysfunction	I-Disease
+and	O
+ascending	O
+paralysis	B-Disease
+.	O
+
+Histological	O
+and	O
+immunohistochemical	O
+investigations	O
+(	O
+HE	O
+-	O
+LFB	O
+,	O
+CD	O
+-	O
+68	O
+,	O
+Neurofilament	O
+)	O
+revealed	O
+degeneration	B-Disease
+of	I-Disease
+myelin	I-Disease
+and	I-Disease
+axons	I-Disease
+as	O
+well	O
+as	O
+pseudocystic	B-Disease
+transformation	I-Disease
+in	O
+areas	O
+exposed	O
+to	O
+vincristine	B-Chemical
+,	O
+accompanied	O
+by	O
+secondary	O
+changes	O
+with	O
+numerous	O
+prominent	O
+macrophages	O
+.	O
+
+The	O
+clinical	O
+course	O
+and	O
+histopathological	O
+results	O
+of	O
+the	O
+two	O
+cases	O
+are	O
+presented	O
+.	O
+
+A	O
+review	O
+of	O
+all	O
+reported	O
+cases	O
+in	O
+the	O
+literature	O
+is	O
+given	O
+.	O
+
+A	O
+better	O
+controlled	O
+regimen	O
+for	O
+administering	O
+vincristine	B-Chemical
+and	O
+intrathecal	O
+chemotherapy	O
+is	O
+recommended	O
+.	O
+
+Palpebral	B-Disease
+twitching	I-Disease
+in	O
+a	O
+depressed	B-Disease
+adolescent	O
+on	O
+citalopram	B-Chemical
+.	O
+
+Current	O
+estimates	O
+suggest	O
+that	O
+between	O
+0	O
+.	O
+4	O
+%	O
+and	O
+8	O
+.	O
+3	O
+%	O
+of	O
+children	O
+and	O
+adolescents	O
+are	O
+affected	O
+by	O
+major	B-Disease
+depression	I-Disease
+.	O
+
+We	O
+report	O
+a	O
+favorable	O
+response	O
+to	O
+treatment	O
+with	O
+citalopram	B-Chemical
+by	O
+a	O
+15	O
+-	O
+year	O
+-	O
+old	O
+boy	O
+with	O
+major	B-Disease
+depression	I-Disease
+who	O
+exhibited	O
+palpebral	B-Disease
+twitching	I-Disease
+during	O
+his	O
+first	O
+2	O
+weeks	O
+of	O
+treatment	O
+.	O
+
+This	O
+may	O
+have	O
+been	O
+a	O
+side	O
+effect	O
+of	O
+citalopram	B-Chemical
+as	O
+it	O
+remitted	O
+with	O
+redistribution	O
+of	O
+doses	O
+.	O
+
+The	O
+3	O
+-	O
+week	O
+sulphasalazine	B-Chemical
+syndrome	O
+strikes	O
+again	O
+.	O
+
+A	O
+34	O
+-	O
+year	O
+-	O
+old	O
+lady	O
+developed	O
+a	O
+constellation	O
+of	O
+dermatitis	B-Disease
+,	O
+fever	B-Disease
+,	O
+lymphadenopathy	B-Disease
+and	O
+hepatitis	B-Disease
+,	O
+beginning	O
+on	O
+the	O
+17th	O
+day	O
+of	O
+a	O
+course	O
+of	O
+oral	O
+sulphasalazine	B-Chemical
+for	O
+sero	O
+-	O
+negative	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+.	O
+
+Cervical	O
+and	O
+inguinal	O
+lymph	O
+node	O
+biopsies	O
+showed	O
+the	O
+features	O
+of	O
+severe	O
+necrotising	O
+lymphadenitis	B-Disease
+,	O
+associated	O
+with	O
+erythrophagocytosis	O
+and	O
+prominent	O
+eosinophilic	O
+infiltrates	O
+,	O
+without	O
+viral	O
+inclusion	O
+bodies	O
+,	O
+suggestive	O
+of	O
+an	O
+adverse	B-Disease
+drug	I-Disease
+reaction	I-Disease
+.	O
+A	O
+week	O
+later	O
+,	O
+fulminant	O
+drug	B-Disease
+-	I-Disease
+induced	I-Disease
+hepatitis	I-Disease
+,	O
+associated	O
+with	O
+the	O
+presence	O
+of	O
+anti	O
+-	O
+nuclear	O
+autoantibodies	O
+(	O
+but	O
+not	O
+with	O
+other	O
+markers	O
+of	O
+autoimmunity	B-Disease
+)	O
+,	O
+and	O
+accompanied	O
+by	O
+multi	B-Disease
+-	I-Disease
+organ	I-Disease
+failure	I-Disease
+and	O
+sepsis	B-Disease
+,	O
+supervened	O
+.	O
+
+She	O
+subsequently	O
+died	O
+some	O
+5	O
+weeks	O
+after	O
+the	O
+commencement	O
+of	O
+her	O
+drug	O
+therapy	O
+.	O
+Post	O
+-	O
+mortem	O
+examination	O
+showed	O
+evidence	O
+of	O
+massive	B-Disease
+hepatocellular	I-Disease
+necrosis	I-Disease
+,	O
+acute	O
+hypersensitivity	O
+myocarditis	B-Disease
+,	O
+focal	O
+acute	O
+tubulo	O
+-	O
+interstitial	O
+nephritis	B-Disease
+and	O
+extensive	O
+bone	B-Disease
+marrow	I-Disease
+necrosis	I-Disease
+,	O
+with	O
+no	O
+evidence	O
+of	O
+malignancy	B-Disease
+.	O
+
+It	O
+is	O
+thought	O
+that	O
+the	O
+clinico	O
+-	O
+pathological	O
+features	O
+and	O
+chronology	O
+of	O
+this	O
+case	O
+bore	O
+the	O
+hallmarks	O
+of	O
+the	O
+so	O
+-	O
+called	O
+"	O
+3	O
+-	O
+week	O
+sulphasalazine	B-Chemical
+syndrome	O
+"	O
+,	O
+a	O
+rare	O
+,	O
+but	O
+often	O
+fatal	O
+,	O
+immunoallergic	O
+reaction	O
+to	O
+sulphasalazine	B-Chemical
+.	O
+
+Intravenous	O
+administration	O
+of	O
+prochlorperazine	B-Chemical
+by	O
+15	O
+-	O
+minute	O
+infusion	O
+versus	O
+2	O
+-	O
+minute	O
+bolus	O
+does	O
+not	O
+affect	O
+the	O
+incidence	O
+of	O
+akathisia	B-Disease
+:	O
+a	O
+prospective	O
+,	O
+randomized	O
+,	O
+controlled	O
+trial	O
+.	O
+
+STUDY	O
+OBJECTIVE	O
+:	O
+We	O
+sought	O
+to	O
+compare	O
+the	O
+rate	O
+of	O
+akathisia	B-Disease
+after	O
+administration	O
+of	O
+intravenous	O
+prochlorperazine	B-Chemical
+as	O
+a	O
+2	O
+-	O
+minute	O
+bolus	O
+or	O
+15	O
+-	O
+minute	O
+infusion	O
+.	O
+
+METHODS	O
+:	O
+We	O
+conducted	O
+a	O
+prospective	O
+,	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+study	O
+in	O
+the	O
+emergency	O
+department	O
+of	O
+a	O
+central	O
+-	O
+city	O
+teaching	O
+hospital	O
+.	O
+
+Patients	O
+aged	O
+18	O
+years	O
+or	O
+older	O
+treated	O
+with	O
+prochlorperazine	B-Chemical
+for	O
+headache	B-Disease
+,	O
+nausea	B-Disease
+,	O
+or	O
+vomiting	B-Disease
+were	O
+eligible	O
+for	O
+inclusion	O
+.	O
+
+Study	O
+participants	O
+were	O
+randomized	O
+to	O
+receive	O
+10	O
+mg	O
+of	O
+prochlorperazine	B-Chemical
+administered	O
+intravenously	O
+by	O
+means	O
+of	O
+2	O
+-	O
+minute	O
+push	O
+(	O
+bolus	O
+group	O
+)	O
+or	O
+10	O
+mg	O
+diluted	O
+in	O
+50	O
+mL	O
+of	O
+normal	O
+saline	O
+solution	O
+administered	O
+by	O
+means	O
+of	O
+intravenous	O
+infusion	O
+during	O
+a	O
+15	O
+-	O
+minute	O
+period	O
+(	O
+infusion	O
+group	O
+)	O
+.	O
+
+The	O
+main	O
+outcome	O
+was	O
+the	O
+number	O
+of	O
+study	O
+participants	O
+experiencing	O
+akathisia	B-Disease
+within	O
+60	O
+minutes	O
+of	O
+administration	O
+.	O
+
+Akathisia	O
+was	O
+defined	O
+as	O
+either	O
+a	O
+spontaneous	O
+report	O
+of	O
+restlessness	O
+or	O
+agitation	B-Disease
+or	O
+a	O
+change	O
+of	O
+2	O
+or	O
+more	O
+in	O
+the	O
+patient	O
+-	O
+reported	O
+akathisia	B-Disease
+rating	O
+scale	O
+and	O
+a	O
+change	O
+of	O
+at	O
+least	O
+1	O
+in	O
+the	O
+investigator	O
+-	O
+observed	O
+akathisia	B-Disease
+rating	O
+scale	O
+.	O
+
+The	O
+intensity	O
+of	O
+headache	B-Disease
+and	O
+nausea	B-Disease
+was	O
+measured	O
+with	O
+a	O
+100	O
+-	O
+mm	O
+visual	O
+analog	O
+scale	O
+.	O
+
+RESULTS	O
+:	O
+One	O
+hundred	O
+patients	O
+were	O
+enrolled	O
+.	O
+
+One	O
+study	O
+participant	O
+was	O
+excluded	O
+after	O
+protocol	O
+violation	O
+.	O
+
+Seventy	O
+-	O
+three	O
+percent	O
+(	O
+73	O
+/	O
+99	O
+)	O
+of	O
+the	O
+study	O
+participants	O
+were	O
+treated	O
+for	O
+headache	B-Disease
+and	O
+70	O
+%	O
+(	O
+70	O
+/	O
+99	O
+)	O
+for	O
+nausea	B-Disease
+.	O
+
+In	O
+the	O
+bolus	O
+group	O
+,	O
+26	O
+.	O
+0	O
+%	O
+(	O
+13	O
+/	O
+50	O
+)	O
+had	O
+akathisia	B-Disease
+compared	O
+with	O
+32	O
+.	O
+7	O
+%	O
+(	O
+16	O
+/	O
+49	O
+)	O
+in	O
+the	O
+infusion	O
+group	O
+(	O
+Delta	O
+=	O
+-	O
+6	O
+.	O
+7	O
+%	O
+;	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+-	O
+24	O
+.	O
+6	O
+%	O
+to	O
+11	O
+.	O
+2	O
+%	O
+)	O
+.	O
+
+The	O
+difference	O
+between	O
+the	O
+bolus	O
+and	O
+infusion	O
+groups	O
+in	O
+the	O
+percentage	O
+of	O
+participants	O
+who	O
+saw	O
+a	O
+50	O
+%	O
+reduction	O
+in	O
+their	O
+headache	B-Disease
+intensity	O
+within	O
+30	O
+minutes	O
+was	O
+11	O
+.	O
+8	O
+%	O
+(	O
+95	O
+%	O
+CI	O
+-	O
+9	O
+.	O
+6	O
+%	O
+to	O
+33	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+The	O
+difference	O
+in	O
+the	O
+percentage	O
+of	O
+patients	O
+with	O
+a	O
+50	O
+%	O
+reduction	O
+in	O
+their	O
+nausea	B-Disease
+was	O
+12	O
+.	O
+6	O
+%	O
+(	O
+95	O
+%	O
+CI	O
+-	O
+4	O
+.	O
+6	O
+%	O
+to	O
+29	O
+.	O
+8	O
+%	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+A	O
+50	O
+%	O
+reduction	O
+in	O
+the	O
+incidence	O
+of	O
+akathisia	B-Disease
+when	O
+prochlorperazine	B-Chemical
+was	O
+administered	O
+by	O
+means	O
+of	O
+15	O
+-	O
+minute	O
+intravenous	O
+infusion	O
+versus	O
+a	O
+2	O
+-	O
+minute	O
+intravenous	O
+push	O
+was	O
+not	O
+detected	O
+.	O
+
+The	O
+efficacy	O
+of	O
+prochlorperazine	B-Chemical
+in	O
+the	O
+treatment	O
+of	O
+headache	B-Disease
+and	O
+nausea	B-Disease
+likewise	O
+did	O
+not	O
+appear	O
+to	O
+be	O
+affected	O
+by	O
+the	O
+rate	O
+of	O
+administration	O
+,	O
+although	O
+no	O
+formal	O
+statistical	O
+comparisons	O
+were	O
+made	O
+.	O
+
+Combined	O
+antiretroviral	O
+therapy	O
+causes	O
+cardiomyopathy	B-Disease
+and	O
+elevates	O
+plasma	O
+lactate	B-Chemical
+in	O
+transgenic	O
+AIDS	B-Disease
+mice	O
+.	O
+
+Highly	O
+active	O
+antiretroviral	O
+therapy	O
+(	O
+HAART	O
+)	O
+is	O
+implicated	O
+in	O
+cardiomyopathy	B-Disease
+(	O
+CM	B-Disease
+)	O
+and	O
+in	O
+elevated	O
+plasma	O
+lactate	B-Chemical
+(	O
+LA	B-Chemical
+)	O
+in	O
+AIDS	B-Disease
+through	O
+mechanisms	O
+of	O
+mitochondrial	B-Disease
+dysfunction	I-Disease
+.	O
+
+To	O
+determine	O
+mitochondrial	O
+events	O
+from	O
+HAART	O
+in	O
+vivo	O
+,	O
+8	O
+-	O
+week	O
+-	O
+old	O
+hemizygous	O
+transgenic	O
+AIDS	B-Disease
+mice	O
+(	O
+NL4	O
+-	O
+3Delta	O
+gag	O
+/	O
+pol	O
+;	O
+TG	O
+)	O
+and	O
+wild	O
+-	O
+type	O
+FVB	O
+/	O
+n	O
+littermates	O
+were	O
+treated	O
+with	O
+the	O
+HAART	O
+combination	O
+of	O
+zidovudine	B-Chemical
+,	O
+lamivudine	B-Chemical
+,	O
+and	O
+indinavir	B-Chemical
+or	O
+vehicle	O
+control	O
+for	O
+10	O
+days	O
+or	O
+35	O
+days	O
+.	O
+
+At	O
+termination	O
+of	O
+the	O
+experiments	O
+,	O
+mice	O
+underwent	O
+echocardiography	O
+,	O
+quantitation	O
+of	O
+abundance	O
+of	O
+molecular	O
+markers	O
+of	O
+CM	B-Disease
+(	O
+ventricular	O
+mRNA	O
+encoding	O
+atrial	O
+natriuretic	O
+factor	O
+[	O
+ANF	O
+]	O
+and	O
+sarcoplasmic	O
+calcium	B-Chemical
+ATPase	O
+[	O
+SERCA2	O
+]	O
+)	O
+,	O
+and	O
+determination	O
+of	O
+plasma	O
+LA	B-Chemical
+.	O
+
+Myocardial	O
+histologic	O
+features	O
+were	O
+analyzed	O
+semiquantitatively	O
+and	O
+results	O
+were	O
+confirmed	O
+by	O
+transmission	O
+electron	O
+microscopy	O
+.	O
+
+After	O
+35	O
+days	O
+in	O
+the	O
+TG	O
++	O
+HAART	O
+cohort	O
+,	O
+left	O
+ventricular	O
+mass	O
+increased	O
+160	O
+%	O
+by	O
+echocardiography	O
+.	O
+
+Molecularly	O
+,	O
+ANF	O
+mRNA	O
+increased	O
+250	O
+%	O
+and	O
+SERCA2	O
+mRNA	O
+decreased	O
+57	O
+%	O
+.	O
+
+Biochemically	O
+,	O
+LA	B-Chemical
+was	O
+elevated	O
+(	O
+8	O
+.	O
+5	O
++	O
+/	O
+-	O
+2	O
+.	O
+0	O
+mM	O
+)	O
+.	O
+
+Pathologically	O
+,	O
+granular	O
+cytoplasmic	O
+changes	O
+were	O
+found	O
+in	O
+cardiac	O
+myocytes	O
+,	O
+indicating	O
+enlarged	O
+,	O
+damaged	O
+mitochondria	O
+.	O
+
+Findings	O
+were	O
+confirmed	O
+ultrastructurally	O
+.	O
+
+No	O
+changes	O
+were	O
+found	O
+in	O
+other	O
+cohorts	O
+.	O
+
+After	O
+10	O
+days	O
+,	O
+only	O
+ANF	O
+was	O
+elevated	O
+,	O
+and	O
+only	O
+in	O
+the	O
+TG	O
++	O
+HAART	O
+cohort	O
+.	O
+
+Results	O
+show	O
+that	O
+cumulative	O
+HAART	O
+caused	O
+mitochondrial	O
+CM	B-Disease
+with	O
+elevated	O
+LA	B-Chemical
+in	O
+AIDS	B-Disease
+transgenic	O
+mice	O
+.	O
+
+A	O
+Phase	O
+II	O
+trial	O
+of	O
+cisplatin	B-Chemical
+plus	O
+WR	B-Chemical
+-	I-Chemical
+2721	I-Chemical
+(	O
+amifostine	B-Chemical
+)	O
+for	O
+metastatic	O
+breast	B-Disease
+carcinoma	I-Disease
+:	O
+an	O
+Eastern	O
+Cooperative	O
+Oncology	O
+Group	O
+Study	O
+(	O
+E8188	O
+)	O
+.	O
+
+BACKGROUND	O
+:	O
+Cisplatin	B-Chemical
+has	O
+minimal	O
+antitumor	O
+activity	O
+when	O
+used	O
+as	O
+second	O
+-	O
+or	O
+third	O
+-	O
+line	O
+treatment	O
+of	O
+metastatic	O
+breast	B-Disease
+carcinoma	I-Disease
+.	O
+
+Older	O
+reports	O
+suggest	O
+an	O
+objective	O
+response	O
+rate	O
+of	O
+8	O
+%	O
+when	O
+60	O
+-	O
+120	O
+mg	O
+/	O
+m2	O
+of	O
+cisplatin	B-Chemical
+is	O
+administered	O
+every	O
+3	O
+-	O
+4	O
+weeks	O
+.	O
+
+Although	O
+a	O
+dose	O
+-	O
+response	O
+effect	O
+has	O
+been	O
+observed	O
+with	O
+cisplatin	B-Chemical
+,	O
+the	O
+dose	O
+-	O
+limiting	O
+toxicities	B-Disease
+associated	O
+with	O
+cisplatin	B-Chemical
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+nephrotoxicity	B-Disease
+,	O
+ototoxicity	B-Disease
+,	O
+and	O
+neurotoxicity	B-Disease
+)	O
+have	O
+limited	O
+its	O
+use	O
+as	O
+a	O
+treatment	O
+for	O
+breast	B-Disease
+carcinoma	I-Disease
+.	O
+
+WR	B-Chemical
+-	I-Chemical
+2721	I-Chemical
+or	O
+amifostine	B-Chemical
+initially	O
+was	O
+developed	O
+to	O
+protect	O
+military	O
+personnel	O
+in	O
+the	O
+event	O
+of	O
+nuclear	O
+war	O
+.	O
+
+Amifostine	B-Chemical
+subsequently	O
+was	O
+shown	O
+to	O
+protect	O
+normal	O
+tissues	O
+from	O
+the	O
+toxic	O
+effects	O
+of	O
+alkylating	B-Chemical
+agents	I-Chemical
+and	O
+cisplatin	B-Chemical
+without	O
+decreasing	O
+the	O
+antitumor	O
+effect	O
+of	O
+the	O
+chemotherapy	O
+.	O
+
+Early	O
+trials	O
+of	O
+cisplatin	B-Chemical
+and	O
+amifostine	B-Chemical
+also	O
+suggested	O
+that	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+cisplatin	B-Chemical
+-	O
+induced	O
+nephrotoxicity	B-Disease
+,	O
+ototoxicity	B-Disease
+,	O
+and	O
+neuropathy	B-Disease
+were	O
+reduced	O
+.	O
+
+METHODS	O
+:	O
+A	O
+Phase	O
+II	O
+study	O
+of	O
+the	O
+combination	O
+of	O
+cisplatin	B-Chemical
+plus	O
+amifostine	B-Chemical
+was	O
+conducted	O
+in	O
+patients	O
+with	O
+progressive	O
+metastatic	O
+breast	B-Disease
+carcinoma	I-Disease
+who	O
+had	O
+received	O
+one	O
+,	O
+but	O
+not	O
+more	O
+than	O
+one	O
+,	O
+chemotherapy	O
+regimen	O
+for	O
+metastatic	O
+disease	O
+.	O
+
+Patients	O
+received	O
+amifostine	B-Chemical
+,	O
+910	O
+mg	O
+/	O
+m2	O
+intravenously	O
+over	O
+15	O
+minutes	O
+.	O
+
+After	O
+completion	O
+of	O
+the	O
+amifostine	B-Chemical
+infusion	O
+,	O
+cisplatin	B-Chemical
+120	O
+mg	O
+/	O
+m2	O
+was	O
+administered	O
+over	O
+30	O
+minutes	O
+.	O
+
+Intravenous	O
+hydration	O
+and	O
+mannitol	B-Chemical
+was	O
+administered	O
+before	O
+and	O
+after	O
+cisplatin	B-Chemical
+.	O
+
+Treatment	O
+was	O
+administered	O
+every	O
+3	O
+weeks	O
+until	O
+disease	O
+progression	O
+.	O
+
+RESULTS	O
+:	O
+Forty	O
+-	O
+four	O
+patients	O
+were	O
+enrolled	O
+in	O
+the	O
+study	O
+of	O
+which	O
+7	O
+(	O
+16	O
+%	O
+)	O
+were	O
+ineligible	O
+.	O
+
+A	O
+median	O
+of	O
+2	O
+cycles	O
+of	O
+therapy	O
+was	O
+administered	O
+to	O
+the	O
+37	O
+eligible	O
+patients	O
+.	O
+
+Six	O
+partial	O
+responses	O
+were	O
+observed	O
+for	O
+an	O
+overall	O
+response	O
+rate	O
+of	O
+16	O
+%	O
+.	O
+
+Most	O
+patients	O
+(	O
+57	O
+%	O
+)	O
+stopped	O
+treatment	O
+because	O
+of	O
+disease	O
+progression	O
+.	O
+
+Neurologic	B-Disease
+toxicity	I-Disease
+was	O
+reported	O
+in	O
+52	O
+%	O
+of	O
+patients	O
+.	O
+
+Seven	O
+different	O
+life	O
+-	O
+threatening	O
+toxicities	B-Disease
+were	O
+observed	O
+in	O
+patients	O
+while	O
+receiving	O
+treatment	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+combination	O
+of	O
+cisplatin	B-Chemical
+and	O
+amifostine	B-Chemical
+in	O
+this	O
+study	O
+resulted	O
+in	O
+an	O
+overall	O
+response	O
+rate	O
+of	O
+16	O
+%	O
+.	O
+
+Neither	O
+a	O
+tumor	B-Disease
+-	O
+protective	O
+effect	O
+nor	O
+reduced	O
+toxicity	B-Disease
+to	O
+normal	O
+tissues	O
+was	O
+observed	O
+with	O
+the	O
+addition	O
+of	O
+amifostine	B-Chemical
+to	O
+cisplatin	B-Chemical
+in	O
+this	O
+trial	O
+.	O
+
+Oral	B-Chemical
+contraceptives	I-Chemical
+and	O
+the	O
+risk	O
+of	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+An	O
+association	O
+between	O
+the	O
+use	O
+of	O
+oral	B-Chemical
+contraceptives	I-Chemical
+and	O
+the	O
+risk	O
+of	O
+myocardial	B-Disease
+infarction	I-Disease
+has	O
+been	O
+found	O
+in	O
+some	O
+,	O
+but	O
+not	O
+all	O
+,	O
+studies	O
+.	O
+
+We	O
+investigated	O
+this	O
+association	O
+,	O
+according	O
+to	O
+the	O
+type	O
+of	O
+progestagen	B-Chemical
+included	O
+in	O
+third	O
+-	O
+generation	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+desogestrel	B-Chemical
+or	O
+gestodene	B-Chemical
+)	O
+and	O
+second	O
+-	O
+generation	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+levonorgestrel	B-Chemical
+)	O
+oral	B-Chemical
+contraceptives	I-Chemical
+,	O
+the	O
+dose	O
+of	O
+estrogen	B-Chemical
+,	O
+and	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+prothrombotic	O
+mutations	O
+METHODS	O
+:	O
+In	O
+a	O
+nationwide	O
+,	O
+population	O
+-	O
+based	O
+,	O
+case	O
+-	O
+control	O
+study	O
+,	O
+we	O
+identified	O
+and	O
+enrolled	O
+248	O
+women	O
+18	O
+through	O
+49	O
+years	O
+of	O
+age	O
+who	O
+had	O
+had	O
+a	O
+first	O
+myocardial	B-Disease
+infarction	I-Disease
+between	O
+1990	O
+and	O
+1995	O
+and	O
+925	O
+control	O
+women	O
+who	O
+had	O
+not	O
+had	O
+a	O
+myocardial	B-Disease
+infarction	I-Disease
+and	O
+who	O
+were	O
+matched	O
+for	O
+age	O
+,	O
+calendar	O
+year	O
+of	O
+the	O
+index	O
+event	O
+,	O
+and	O
+area	O
+of	O
+residence	O
+.	O
+
+Subjects	O
+supplied	O
+information	O
+on	O
+oral	B-Chemical
+-	I-Chemical
+contraceptive	I-Chemical
+use	O
+and	O
+major	O
+cardiovascular	O
+risk	O
+factors	O
+.	O
+
+An	O
+analysis	O
+for	O
+factor	O
+V	O
+Leiden	O
+and	O
+the	O
+G20210A	O
+mutation	O
+in	O
+the	O
+prothrombin	O
+gene	O
+was	O
+conducted	O
+in	O
+217	O
+patients	O
+and	O
+763	O
+controls	O
+RESULTS	O
+:	O
+The	O
+odds	O
+ratio	O
+for	O
+myocardial	B-Disease
+infarction	I-Disease
+among	O
+women	O
+who	O
+used	O
+any	O
+type	O
+of	O
+combined	O
+oral	B-Chemical
+contraceptive	I-Chemical
+,	O
+as	O
+compared	O
+with	O
+nonusers	O
+,	O
+was	O
+2	O
+.	O
+0	O
+(	O
+95	O
+percent	O
+confidence	O
+interval	O
+,	O
+1	O
+.	O
+5	O
+to	O
+2	O
+.	O
+8	O
+)	O
+.	O
+
+The	O
+adjusted	O
+odds	O
+ratio	O
+was	O
+2	O
+.	O
+5	O
+(	O
+95	O
+percent	O
+confidence	O
+interval	O
+,	O
+1	O
+.	O
+5	O
+to	O
+4	O
+.	O
+1	O
+)	O
+among	O
+women	O
+who	O
+used	O
+second	O
+-	O
+generation	O
+oral	B-Chemical
+contraceptives	I-Chemical
+and	O
+1	O
+.	O
+3	O
+(	O
+95	O
+percent	O
+confidence	O
+interval	O
+,	O
+0	O
+.	O
+7	O
+to	O
+2	O
+.	O
+5	O
+)	O
+among	O
+those	O
+who	O
+used	O
+third	O
+-	O
+generation	O
+oral	B-Chemical
+contraceptives	I-Chemical
+.	O
+
+Among	O
+women	O
+who	O
+used	O
+oral	B-Chemical
+contraceptives	I-Chemical
+,	O
+the	O
+odds	O
+ratio	O
+was	O
+2	O
+.	O
+1	O
+(	O
+95	O
+percent	O
+confidence	O
+interval	O
+,	O
+1	O
+.	O
+5	O
+to	O
+3	O
+.	O
+0	O
+)	O
+for	O
+those	O
+without	O
+a	O
+prothrombotic	O
+mutation	O
+and	O
+1	O
+.	O
+9	O
+(	O
+95	O
+percent	O
+confidence	O
+interval	O
+,	O
+0	O
+.	O
+6	O
+to	O
+5	O
+.	O
+5	O
+)	O
+for	O
+those	O
+with	O
+a	O
+mutation	O
+CONCLUSIONS	O
+:	O
+The	O
+risk	O
+of	O
+myocardial	B-Disease
+infarction	I-Disease
+was	O
+increased	O
+among	O
+women	O
+who	O
+used	O
+second	O
+-	O
+generation	O
+oral	B-Chemical
+contraceptives	I-Chemical
+.	O
+
+The	O
+results	O
+with	O
+respect	O
+to	O
+the	O
+use	O
+of	O
+third	O
+-	O
+generation	O
+oral	B-Chemical
+contraceptives	I-Chemical
+were	O
+inconclusive	O
+but	O
+suggested	O
+that	O
+the	O
+risk	O
+was	O
+lower	O
+than	O
+the	O
+risk	O
+associated	O
+with	O
+second	O
+-	O
+generation	O
+oral	B-Chemical
+contraceptives	I-Chemical
+.	O
+
+The	O
+risk	O
+of	O
+myocardial	B-Disease
+infarction	I-Disease
+was	O
+similar	O
+among	O
+women	O
+who	O
+used	O
+oral	B-Chemical
+contraceptives	I-Chemical
+whether	O
+or	O
+not	O
+they	O
+had	O
+a	O
+prothrombotic	O
+mutation	O
+.	O
+
+End	B-Disease
+-	I-Disease
+stage	I-Disease
+renal	I-Disease
+disease	I-Disease
+(	O
+ESRD	B-Disease
+)	O
+after	O
+orthotopic	O
+liver	O
+transplantation	O
+(	O
+OLTX	O
+)	O
+using	O
+calcineurin	O
+-	O
+based	O
+immunotherapy	O
+:	O
+risk	O
+of	O
+development	O
+and	O
+treatment	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+calcineurin	O
+inhibitors	O
+cyclosporine	B-Chemical
+and	O
+tacrolimus	B-Chemical
+are	O
+both	O
+known	O
+to	O
+be	O
+nephrotoxic	B-Disease
+.	O
+
+Their	O
+use	O
+in	O
+orthotopic	O
+liver	O
+transplantation	O
+(	O
+OLTX	O
+)	O
+has	O
+dramatically	O
+improved	O
+success	O
+rates	O
+.	O
+
+Recently	O
+,	O
+however	O
+,	O
+we	O
+have	O
+had	O
+an	O
+increase	O
+of	O
+patients	O
+who	O
+are	O
+presenting	O
+after	O
+OLTX	O
+with	O
+end	B-Disease
+-	I-Disease
+stage	I-Disease
+renal	I-Disease
+disease	I-Disease
+(	O
+ESRD	B-Disease
+)	O
+.	O
+
+This	O
+retrospective	O
+study	O
+examines	O
+the	O
+incidence	O
+and	O
+treatment	O
+of	O
+ESRD	B-Disease
+and	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+(	O
+CRF	B-Disease
+)	O
+in	O
+OLTX	O
+patients	O
+.	O
+
+METHODS	O
+:	O
+Patients	O
+receiving	O
+an	O
+OLTX	O
+only	O
+from	O
+June	O
+1985	O
+through	O
+December	O
+of	O
+1994	O
+who	O
+survived	O
+6	O
+months	O
+postoperatively	O
+were	O
+studied	O
+(	O
+n	O
+=	O
+834	O
+)	O
+.	O
+
+Our	O
+prospectively	O
+collected	O
+database	O
+was	O
+the	O
+source	O
+of	O
+information	O
+.	O
+
+Patients	O
+were	O
+divided	O
+into	O
+three	O
+groups	O
+:	O
+Controls	O
+,	O
+no	O
+CRF	B-Disease
+or	O
+ESRD	B-Disease
+,	O
+n	O
+=	O
+748	O
+;	O
+CRF	B-Disease
+,	O
+sustained	O
+serum	O
+creatinine	B-Chemical
+>	O
+2	O
+.	O
+5	O
+mg	O
+/	O
+dl	O
+,	O
+n	O
+=	O
+41	O
+;	O
+and	O
+ESRD	B-Disease
+,	O
+n	O
+=	O
+45	O
+.	O
+
+Groups	O
+were	O
+compared	O
+for	O
+preoperative	O
+laboratory	O
+variables	O
+,	O
+diagnosis	O
+,	O
+postoperative	O
+variables	O
+,	O
+survival	O
+,	O
+type	O
+of	O
+ESRD	B-Disease
+therapy	O
+,	O
+and	O
+survival	O
+from	O
+onset	O
+of	O
+ESRD	B-Disease
+.	O
+
+RESULTS	O
+:	O
+At	O
+13	O
+years	O
+after	O
+OLTX	O
+,	O
+the	O
+incidence	O
+of	O
+severe	O
+renal	B-Disease
+dysfunction	I-Disease
+was	O
+18	O
+.	O
+1	O
+%	O
+(	O
+CRF	B-Disease
+8	O
+.	O
+6	O
+%	O
+and	O
+ESRD	B-Disease
+9	O
+.	O
+5	O
+%	O
+)	O
+.	O
+
+Compared	O
+with	O
+control	O
+patients	O
+,	O
+CRF	B-Disease
+and	O
+ESRD	B-Disease
+patients	O
+had	O
+higher	O
+preoperative	O
+serum	O
+creatinine	B-Chemical
+levels	O
+,	O
+a	O
+greater	O
+percentage	O
+of	O
+patients	O
+with	O
+hepatorenal	B-Disease
+syndrome	I-Disease
+,	O
+higher	O
+percentage	O
+requirement	O
+for	O
+dialysis	O
+in	O
+the	O
+first	O
+3	O
+months	O
+postoperatively	O
+,	O
+and	O
+a	O
+higher	O
+1	O
+-	O
+year	O
+serum	O
+creatinine	B-Chemical
+.	O
+
+Multivariate	O
+stepwise	O
+logistic	O
+regression	O
+analysis	O
+using	O
+preoperative	O
+and	O
+postoperative	O
+variables	O
+identified	O
+that	O
+an	O
+increase	O
+of	O
+serum	O
+creatinine	B-Chemical
+compared	O
+with	O
+average	O
+at	O
+1	O
+year	O
+,	O
+3	O
+months	O
+,	O
+and	O
+4	O
+weeks	O
+postoperatively	O
+were	O
+independent	O
+risk	O
+factors	O
+for	O
+the	O
+development	O
+of	O
+CRF	B-Disease
+or	O
+ESRD	B-Disease
+with	O
+odds	O
+ratios	O
+of	O
+2	O
+.	O
+6	O
+,	O
+2	O
+.	O
+2	O
+,	O
+and	O
+1	O
+.	O
+6	O
+,	O
+respectively	O
+.	O
+
+Overall	O
+survival	O
+from	O
+the	O
+time	O
+of	O
+OLTX	O
+was	O
+not	O
+significantly	O
+different	O
+among	O
+groups	O
+,	O
+but	O
+by	O
+year	O
+13	O
+,	O
+the	O
+survival	O
+of	O
+the	O
+patients	O
+who	O
+had	O
+ESRD	B-Disease
+was	O
+only	O
+28	O
+.	O
+2	O
+%	O
+compared	O
+with	O
+54	O
+.	O
+6	O
+%	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+Patients	O
+developing	O
+ESRD	B-Disease
+had	O
+a	O
+6	O
+-	O
+year	O
+survival	O
+after	O
+onset	O
+of	O
+ESRD	B-Disease
+of	O
+27	O
+%	O
+for	O
+the	O
+patients	O
+receiving	O
+hemodialysis	O
+versus	O
+71	O
+.	O
+4	O
+%	O
+for	O
+the	O
+patients	O
+developing	O
+ESRD	B-Disease
+who	O
+subsequently	O
+received	O
+kidney	O
+transplants	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Patients	O
+who	O
+are	O
+more	O
+than	O
+10	O
+years	O
+post	O
+-	O
+OLTX	O
+have	O
+CRF	B-Disease
+and	O
+ESRD	B-Disease
+at	O
+a	O
+high	O
+rate	O
+.	O
+
+The	O
+development	O
+of	O
+ESRD	B-Disease
+decreases	O
+survival	O
+,	O
+particularly	O
+in	O
+those	O
+patients	O
+treated	O
+with	O
+dialysis	O
+only	O
+.	O
+
+Patients	O
+who	O
+develop	O
+ESRD	B-Disease
+have	O
+a	O
+higher	O
+preoperative	O
+and	O
+1	O
+-	O
+year	O
+serum	O
+creatinine	B-Chemical
+and	O
+are	O
+more	O
+likely	O
+to	O
+have	O
+hepatorenal	B-Disease
+syndrome	I-Disease
+.	O
+
+However	O
+,	O
+an	O
+increase	O
+of	O
+serum	O
+creatinine	B-Chemical
+at	O
+various	O
+times	O
+postoperatively	O
+is	O
+more	O
+predictive	O
+of	O
+the	O
+development	O
+of	O
+CRF	B-Disease
+or	O
+ESRD	B-Disease
+.	O
+
+New	O
+strategies	O
+for	O
+long	O
+-	O
+term	O
+immunosuppression	O
+may	O
+be	O
+needed	O
+to	O
+decrease	O
+this	O
+complication	O
+.	O
+
+Epileptic	B-Disease
+seizures	I-Disease
+following	O
+cortical	O
+application	O
+of	O
+fibrin	O
+sealants	O
+containing	O
+tranexamic	B-Chemical
+acid	I-Chemical
+in	O
+rats	O
+.	O
+
+BACKGROUND	O
+:	O
+Fibrin	O
+sealants	O
+(	O
+FS	O
+)	O
+derived	O
+from	O
+human	O
+plasma	O
+are	O
+frequently	O
+used	O
+in	O
+neurosurgery	O
+.	O
+
+In	O
+order	O
+to	O
+increase	O
+clot	O
+stability	O
+,	O
+FS	O
+typically	O
+contain	O
+aprotinin	O
+,	O
+a	O
+natural	O
+fibrinolysis	O
+inhibitor	O
+.	O
+
+Recently	O
+,	O
+synthetic	O
+fibrinolysis	O
+inhibitors	O
+such	O
+as	O
+tranexamic	B-Chemical
+acid	I-Chemical
+(	O
+tAMCA	B-Chemical
+)	O
+have	O
+been	O
+considered	O
+as	O
+substitutes	O
+for	O
+aprotinin	O
+.	O
+
+However	O
+,	O
+tAMCA	B-Chemical
+has	O
+been	O
+shown	O
+to	O
+cause	O
+epileptic	B-Disease
+seizures	I-Disease
+.	O
+
+We	O
+wanted	O
+to	O
+study	O
+whether	O
+tAMCA	B-Chemical
+retains	O
+its	O
+convulsive	B-Disease
+action	O
+if	O
+incorporated	O
+into	O
+a	O
+FS	O
+.	O
+
+METHOD	O
+:	O
+FS	O
+containing	O
+aprotinin	O
+or	O
+different	O
+concentrations	O
+of	O
+tAMCA	B-Chemical
+(	O
+0	O
+.	O
+5	O
+-	O
+47	O
+.	O
+5	O
+mg	O
+/	O
+ml	O
+)	O
+were	O
+applied	O
+to	O
+the	O
+pial	O
+surface	O
+of	O
+the	O
+cortex	O
+of	O
+anaesthetized	O
+rats	O
+.	O
+
+The	O
+response	O
+of	O
+the	O
+animals	O
+was	O
+evaluated	O
+using	O
+electroencephalography	O
+and	O
+by	O
+monitoring	O
+the	O
+clinical	O
+behaviour	O
+during	O
+and	O
+after	O
+recovery	O
+from	O
+anaesthesia	O
+.	O
+
+FINDINGS	O
+:	O
+FS	O
+containing	O
+tAMCA	B-Chemical
+caused	O
+paroxysmal	O
+brain	O
+activity	O
+which	O
+was	O
+associated	O
+with	O
+distinct	O
+convulsive	B-Disease
+behaviours	O
+.	O
+
+The	O
+degree	O
+of	O
+these	O
+seizures	B-Disease
+increased	O
+with	O
+increasing	O
+concentration	O
+of	O
+tAMCA	B-Chemical
+.	O
+
+Thus	O
+,	O
+FS	O
+containing	O
+47	O
+.	O
+5	O
+mg	O
+/	O
+ml	O
+tAMCA	B-Chemical
+evoked	O
+generalized	B-Disease
+seizures	I-Disease
+in	O
+all	O
+tested	O
+rats	O
+(	O
+n	O
+=	O
+6	O
+)	O
+while	O
+the	O
+lowest	O
+concentration	O
+of	O
+tAMCA	B-Chemical
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+ml	O
+)	O
+only	O
+evoked	O
+brief	O
+episodes	O
+of	O
+jerk	O
+-	O
+correlated	O
+convulsive	B-Disease
+potentials	O
+in	O
+1	O
+of	O
+6	O
+rats	O
+.	O
+
+In	O
+contrast	O
+,	O
+FS	O
+containing	O
+aprotinin	O
+did	O
+not	O
+evoke	O
+any	O
+paroxysmal	O
+activity	O
+.	O
+
+INTERPRETATION	O
+:	O
+Tranexamic	B-Chemical
+acid	I-Chemical
+retains	O
+its	O
+convulsive	B-Disease
+action	O
+within	O
+FS	O
+.	O
+
+Thus	O
+,	O
+use	O
+of	O
+FS	O
+containing	O
+tAMCA	B-Chemical
+for	O
+surgery	O
+within	O
+or	O
+close	O
+to	O
+the	O
+CNS	O
+may	O
+pose	O
+a	O
+substantial	O
+risk	O
+to	O
+the	O
+patient	O
+.	O
+
+Sequential	O
+observations	O
+of	O
+exencephaly	B-Disease
+and	O
+subsequent	O
+morphological	O
+changes	O
+by	O
+mouse	O
+exo	O
+utero	O
+development	O
+system	O
+:	O
+analysis	O
+of	O
+the	O
+mechanism	O
+of	O
+transformation	O
+from	O
+exencephaly	B-Disease
+to	O
+anencephaly	B-Disease
+.	O
+
+Anencephaly	B-Disease
+has	O
+been	O
+suggested	O
+to	O
+develop	O
+from	O
+exencephaly	B-Disease
+;	O
+however	O
+,	O
+there	O
+is	O
+little	O
+direct	O
+experimental	O
+evidence	O
+to	O
+support	O
+this	O
+,	O
+and	O
+the	O
+mechanism	O
+of	O
+transformation	O
+remains	O
+unclear	O
+.	O
+
+We	O
+examined	O
+this	O
+theory	O
+using	O
+the	O
+exo	O
+utero	O
+development	O
+system	O
+that	O
+allows	O
+direct	O
+and	O
+sequential	O
+observations	O
+of	O
+mid	O
+-	O
+to	O
+late	O
+-	O
+gestation	O
+mouse	O
+embryos	O
+.	O
+
+We	O
+observed	O
+the	O
+exencephaly	B-Disease
+induced	O
+by	O
+5	B-Chemical
+-	I-Chemical
+azacytidine	I-Chemical
+at	O
+embryonic	O
+day	O
+13	O
+.	O
+5	O
+(	O
+E13	O
+.	O
+5	O
+)	O
+,	O
+let	O
+the	O
+embryos	O
+develop	O
+exo	O
+utero	O
+until	O
+E18	O
+.	O
+5	O
+,	O
+and	O
+re	O
+-	O
+observed	O
+the	O
+same	O
+embryos	O
+at	O
+E18	O
+.	O
+5	O
+.	O
+
+We	O
+confirmed	O
+several	O
+cases	O
+of	O
+transformation	O
+from	O
+exencephaly	B-Disease
+to	O
+anencephaly	B-Disease
+.	O
+
+However	O
+,	O
+in	O
+many	O
+cases	O
+,	O
+the	O
+exencephalic	B-Disease
+brain	O
+tissue	O
+was	O
+preserved	O
+with	O
+more	O
+or	O
+less	O
+reduction	O
+during	O
+this	O
+period	O
+.	O
+
+To	O
+analyze	O
+the	O
+transformation	O
+patterns	O
+,	O
+we	O
+classified	O
+the	O
+exencephaly	B-Disease
+by	O
+size	O
+and	O
+shape	O
+of	O
+the	O
+exencephalic	B-Disease
+tissue	O
+into	O
+several	O
+types	O
+at	O
+E13	O
+.	O
+5	O
+and	O
+E18	O
+.	O
+5	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+the	O
+transformation	O
+of	O
+exencephalic	B-Disease
+tissue	O
+was	O
+not	O
+simply	O
+size	O
+-	O
+dependent	O
+,	O
+and	O
+all	O
+cases	O
+of	O
+anencephaly	B-Disease
+at	O
+E18	O
+.	O
+5	O
+resulted	O
+from	O
+embryos	O
+with	O
+a	O
+large	O
+amount	O
+of	O
+exencephalic	B-Disease
+tissue	O
+at	O
+E13	O
+.	O
+5	O
+.	O
+
+Microscopic	O
+observation	O
+showed	O
+the	O
+configuration	O
+of	O
+exencephaly	B-Disease
+at	O
+E13	O
+.	O
+5	O
+,	O
+frequent	O
+hemorrhaging	B-Disease
+and	O
+detachment	O
+of	O
+the	O
+neural	O
+plate	O
+from	O
+surface	O
+ectoderm	O
+in	O
+the	O
+exencephalic	B-Disease
+head	O
+at	O
+E15	O
+.	O
+5	O
+,	O
+and	O
+multiple	O
+modes	O
+of	O
+reduction	O
+in	O
+the	O
+exencephalic	B-Disease
+tissue	O
+at	O
+E18	O
+.	O
+5	O
+.	O
+
+From	O
+observations	O
+of	O
+the	O
+vasculature	O
+,	O
+altered	O
+distribution	O
+patterns	O
+of	O
+vessels	O
+were	O
+identified	O
+in	O
+the	O
+exencephalic	B-Disease
+head	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+overgrowth	O
+of	O
+the	O
+exencephalic	B-Disease
+neural	O
+tissue	O
+causes	O
+the	O
+altered	O
+distribution	O
+patterns	O
+of	O
+vessels	O
+,	O
+subsequent	O
+peripheral	O
+circulatory	B-Disease
+failure	I-Disease
+and	O
+/	O
+or	O
+hemorrhaging	B-Disease
+in	O
+various	O
+parts	O
+of	O
+the	O
+exencephalic	B-Disease
+head	O
+,	O
+leading	O
+to	O
+the	O
+multiple	O
+modes	O
+of	O
+tissue	O
+reduction	O
+during	O
+transformation	O
+from	O
+exencephaly	B-Disease
+to	O
+anencephaly	B-Disease
+.	O
+
+99mTc	B-Chemical
+-	I-Chemical
+glucarate	I-Chemical
+for	O
+detection	O
+of	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Infarct	B-Disease
+-	O
+avid	O
+radiopharmaceuticals	O
+are	O
+necessary	O
+for	O
+rapid	O
+and	O
+timely	O
+diagnosis	O
+of	O
+acute	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+The	O
+animal	O
+model	O
+used	O
+to	O
+produce	O
+infarction	B-Disease
+implies	O
+artery	O
+ligation	O
+but	O
+chemical	O
+induction	O
+can	O
+be	O
+easily	O
+obtained	O
+with	O
+isoproterenol	B-Chemical
+.	O
+
+A	O
+new	O
+infarct	B-Disease
+-	O
+avid	O
+radiopharmaceutical	O
+based	O
+on	O
+glucaric	B-Chemical
+acid	I-Chemical
+was	O
+prepared	O
+in	O
+the	O
+hospital	O
+radiopharmacy	O
+of	O
+the	O
+INCMNSZ	O
+.	O
+
+99mTc	B-Chemical
+-	I-Chemical
+glucarate	I-Chemical
+was	O
+easy	O
+to	O
+prepare	O
+,	O
+stable	O
+for	O
+96	O
+h	O
+and	O
+was	O
+used	O
+to	O
+study	O
+its	O
+biodistribution	O
+in	O
+rats	O
+with	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+acute	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+Histological	O
+studies	O
+demonstrated	O
+that	O
+the	O
+rats	O
+developed	O
+an	O
+infarct	B-Disease
+18	O
+h	O
+after	O
+isoproterenol	B-Chemical
+administration	O
+.	O
+
+The	O
+rat	O
+biodistribution	O
+studies	O
+showed	O
+a	O
+rapid	O
+blood	O
+clearance	O
+via	O
+the	O
+kidneys	O
+.	O
+
+Thirty	O
+minutes	O
+after	O
+99mTc	B-Chemical
+-	I-Chemical
+glucarate	I-Chemical
+administration	O
+the	O
+standardised	O
+heart	O
+uptake	O
+value	O
+S	O
+(	O
+h	O
+)	O
+UV	O
+was	O
+4	O
+.	O
+7	O
+in	O
+infarcted	O
+rat	O
+heart	O
+which	O
+is	O
+six	O
+times	O
+more	O
+than	O
+in	O
+normal	O
+rats	O
+.	O
+
+ROIs	O
+drawn	O
+over	O
+the	O
+gamma	O
+camera	O
+images	O
+showed	O
+a	O
+ratio	O
+of	O
+4	O
+.	O
+4	O
+.	O
+
+The	O
+high	O
+image	O
+quality	O
+suggests	O
+that	O
+high	O
+contrast	O
+images	O
+can	O
+be	O
+obtained	O
+in	O
+humans	O
+and	O
+the	O
+96	O
+h	O
+stability	O
+makes	O
+it	O
+an	O
+ideal	O
+agent	O
+to	O
+detect	O
+,	O
+in	O
+patients	O
+,	O
+early	O
+cardiac	B-Disease
+infarction	I-Disease
+.	O
+
+Bupropion	B-Chemical
+(	O
+Zyban	B-Chemical
+)	O
+toxicity	B-Disease
+.	O
+
+Bupropion	B-Chemical
+is	O
+a	O
+monocyclic	O
+antidepressant	B-Chemical
+structurally	O
+related	O
+to	O
+amphetamine	B-Chemical
+.	O
+
+Zyban	B-Chemical
+,	O
+a	O
+sustained	O
+-	O
+release	O
+formulation	O
+of	O
+bupropion	B-Chemical
+hydrochloride	I-Chemical
+,	O
+was	O
+recently	O
+released	O
+in	O
+Ireland	O
+,	O
+as	O
+a	O
+smoking	O
+cessation	O
+aid	O
+.	O
+
+In	O
+the	O
+initial	O
+6	O
+months	O
+since	O
+it	O
+'	O
+s	O
+introduction	O
+,	O
+12	O
+overdose	B-Disease
+cases	O
+have	O
+been	O
+reported	O
+to	O
+The	O
+National	O
+Poisons	O
+Information	O
+Centre	O
+.	O
+
+8	O
+patients	O
+developed	O
+symptoms	O
+of	O
+toxicity	B-Disease
+.	O
+
+Common	O
+features	O
+included	O
+tachycardia	B-Disease
+,	O
+drowsiness	O
+,	O
+hallucinations	B-Disease
+and	O
+convulsions	B-Disease
+.	O
+
+Two	O
+patients	O
+developed	O
+severe	O
+cardiac	B-Disease
+arrhythmias	I-Disease
+,	O
+including	O
+one	O
+patient	O
+who	O
+was	O
+resuscitated	O
+following	O
+a	O
+cardiac	B-Disease
+arrest	I-Disease
+.	O
+
+All	O
+patients	O
+recovered	O
+without	O
+sequelae	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+a	O
+31	O
+year	O
+old	O
+female	O
+who	O
+required	O
+admission	O
+to	O
+the	O
+Intensive	O
+Care	O
+Unit	O
+for	O
+ventilation	O
+and	O
+full	O
+supportive	O
+therapy	O
+,	O
+following	O
+ingestion	O
+of	O
+13	O
+.	O
+5g	O
+bupropion	B-Chemical
+.	O
+
+Recurrent	O
+seizures	B-Disease
+were	O
+treated	O
+with	O
+diazepam	B-Chemical
+and	O
+broad	O
+complex	O
+tachycardia	B-Disease
+was	O
+successfully	O
+treated	O
+with	O
+adenosine	B-Chemical
+.	O
+
+Zyban	B-Chemical
+caused	O
+significant	O
+neurological	B-Disease
+and	I-Disease
+cardiovascular	I-Disease
+toxicity	I-Disease
+in	O
+overdose	B-Disease
+.	O
+
+The	O
+potential	O
+toxic	O
+effects	O
+should	O
+be	O
+considered	O
+when	O
+prescribing	O
+it	O
+as	O
+a	O
+smoking	O
+cessation	O
+aid	O
+.	O
+
+GLEPP1	O
+receptor	O
+tyrosine	B-Chemical
+phosphatase	O
+(	O
+Ptpro	O
+)	O
+in	O
+rat	O
+PAN	B-Chemical
+nephrosis	B-Disease
+.	O
+
+A	O
+marker	O
+of	O
+acute	O
+podocyte	O
+injury	O
+.	O
+
+Glomerular	O
+epithelial	O
+protein	O
+1	O
+(	O
+GLEPP1	O
+)	O
+is	O
+a	O
+podocyte	O
+receptor	O
+membrane	O
+protein	O
+tyrosine	B-Chemical
+phosphatase	O
+located	O
+on	O
+the	O
+apical	O
+cell	O
+membrane	O
+of	O
+visceral	O
+glomerular	O
+epithelial	O
+cell	O
+and	O
+foot	O
+processes	O
+.	O
+
+This	O
+receptor	O
+plays	O
+a	O
+role	O
+in	O
+regulating	O
+the	O
+structure	O
+and	O
+function	O
+of	O
+podocyte	O
+foot	O
+process	O
+.	O
+
+To	O
+better	O
+understand	O
+the	O
+utility	O
+of	O
+GLEPP1	O
+as	O
+a	O
+marker	O
+of	O
+glomerular	B-Disease
+injury	I-Disease
+,	O
+the	O
+amount	O
+and	O
+distribution	O
+of	O
+GLEPP1	O
+protein	O
+and	O
+mRNA	O
+were	O
+examined	O
+by	O
+immunohistochemistry	O
+,	O
+Western	O
+blot	O
+and	O
+RNase	O
+protection	O
+assay	O
+in	O
+a	O
+model	O
+of	O
+podocyte	O
+injury	O
+in	O
+the	O
+rat	O
+.	O
+
+Puromycin	B-Chemical
+aminonucleoside	I-Chemical
+nephrosis	B-Disease
+was	O
+induced	O
+by	O
+single	O
+intraperitoneal	O
+injection	O
+of	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+(	O
+PAN	B-Chemical
+,	O
+20	O
+mg	O
+/	O
+100g	O
+BW	O
+)	O
+.	O
+
+Tissues	O
+were	O
+analyzed	O
+at	O
+0	O
+,	O
+5	O
+,	O
+7	O
+,	O
+11	O
+,	O
+21	O
+,	O
+45	O
+,	O
+80	O
+and	O
+126	O
+days	O
+after	O
+PAN	B-Chemical
+injection	O
+so	O
+as	O
+to	O
+include	O
+both	O
+the	O
+acute	O
+phase	O
+of	O
+proteinuria	B-Disease
+associated	O
+with	O
+foot	O
+process	O
+effacement	O
+(	O
+days	O
+5	O
+-	O
+11	O
+)	O
+and	O
+the	O
+chronic	O
+phase	O
+of	O
+proteinuria	B-Disease
+associated	O
+with	O
+glomerulosclerosis	B-Disease
+(	O
+days	O
+45	O
+-	O
+126	O
+)	O
+.	O
+
+At	O
+day	O
+5	O
+,	O
+GLEPP1	O
+protein	O
+and	O
+mRNA	O
+were	O
+reduced	O
+from	O
+the	O
+normal	O
+range	O
+(	O
+265	O
+.	O
+2	O
++	O
+/	O
+-	O
+79	O
+.	O
+6	O
+x	O
+10	O
+(	O
+6	O
+)	O
+moles	O
+/	O
+glomerulus	O
+and	O
+100	O
+%	O
+)	O
+to	O
+15	O
+%	O
+of	O
+normal	O
+(	O
+41	O
+.	O
+8	O
++	O
+/	O
+-	O
+4	O
+.	O
+8	O
+x	O
+10	O
+(	O
+6	O
+)	O
+moles	O
+/	O
+glomerulus	O
+,	O
+p	O
+<	O
+0	O
+.	O
+005	O
+)	O
+.	O
+
+This	O
+occurred	O
+in	O
+association	O
+with	O
+an	O
+increase	O
+in	O
+urinary	O
+protein	O
+content	O
+from	O
+1	O
+.	O
+8	O
++	O
+/	O
+-	O
+1	O
+to	O
+99	O
+.	O
+0	O
++	O
+/	O
+-	O
+61	O
+mg	O
+/	O
+day	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+podocalyxin	O
+did	O
+not	O
+change	O
+significantly	O
+at	O
+this	O
+time	O
+.	O
+
+By	O
+day	O
+11	O
+,	O
+GLEPP1	O
+protein	O
+and	O
+mRNA	O
+had	O
+begun	O
+to	O
+return	O
+towards	O
+baseline	O
+.	O
+
+By	O
+day	O
+45	O
+-	O
+126	O
+,	O
+at	O
+a	O
+time	O
+when	O
+glomerular	O
+scarring	O
+was	O
+present	O
+,	O
+GLEPP1	O
+was	O
+absent	O
+from	O
+glomerulosclerotic	O
+areas	O
+although	O
+the	O
+total	O
+glomerular	O
+content	O
+of	O
+GLEPP1	O
+was	O
+not	O
+different	O
+from	O
+normal	O
+.	O
+
+We	O
+conclude	O
+that	O
+GLEPP1	O
+expression	O
+,	O
+unlike	O
+podocalyxin	O
+,	O
+reflects	O
+podocyte	O
+injury	O
+induced	O
+by	O
+PAN	B-Chemical
+.	O
+
+GLEPP1	O
+expression	O
+may	O
+be	O
+a	O
+useful	O
+marker	O
+of	O
+podocyte	O
+injury	O
+.	O
+
+Antithymocyte	B-Chemical
+globulin	I-Chemical
+in	O
+the	O
+treatment	O
+of	O
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+-	O
+induced	O
+aplastic	B-Disease
+anemia	I-Disease
+.	O
+
+A	O
+patient	O
+who	O
+received	O
+antithymocyte	B-Chemical
+globulin	I-Chemical
+therapy	O
+for	O
+aplastic	B-Disease
+anemia	I-Disease
+due	O
+to	O
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+therapy	O
+is	O
+described	O
+.	O
+
+Bone	O
+marrow	O
+recovery	O
+and	O
+peripheral	O
+blood	O
+recovery	O
+were	O
+complete	O
+1	O
+month	O
+and	O
+3	O
+months	O
+,	O
+respectively	O
+,	O
+after	O
+treatment	O
+,	O
+and	O
+blood	O
+transfusion	O
+or	O
+other	O
+therapies	O
+were	O
+not	O
+necessary	O
+in	O
+a	O
+follow	O
+-	O
+up	O
+period	O
+of	O
+more	O
+than	O
+2	O
+years	O
+.	O
+
+Use	O
+of	O
+antithymocyte	B-Chemical
+globulin	I-Chemical
+may	O
+be	O
+the	O
+optimal	O
+treatment	O
+of	O
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+-	O
+induced	O
+aplastic	B-Disease
+anemia	I-Disease
+.	O
+
+Metamizol	B-Chemical
+potentiates	O
+morphine	B-Chemical
+antinociception	O
+but	O
+not	O
+constipation	B-Disease
+after	O
+chronic	O
+treatment	O
+.	O
+
+This	O
+work	O
+evaluates	O
+the	O
+antinociceptive	O
+and	O
+constipating	B-Disease
+effects	O
+of	O
+the	O
+combination	O
+of	O
+3	O
+.	O
+2	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+morphine	B-Chemical
+with	O
+177	O
+.	O
+8	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+metamizol	B-Chemical
+in	O
+acutely	O
+and	O
+chronically	O
+treated	O
+(	O
+once	O
+a	O
+day	O
+for	O
+12	O
+days	O
+)	O
+rats	O
+.	O
+
+On	O
+the	O
+13th	O
+day	O
+,	O
+antinociceptive	O
+effects	O
+were	O
+assessed	O
+using	O
+a	O
+model	O
+of	O
+inflammatory	O
+nociception	O
+,	O
+pain	B-Disease
+-	O
+induced	O
+functional	O
+impairment	O
+model	O
+,	O
+and	O
+the	O
+charcoal	B-Chemical
+meal	O
+test	O
+was	O
+used	O
+to	O
+evaluate	O
+the	O
+intestinal	O
+transit	O
+.	O
+
+Simultaneous	O
+administration	O
+of	O
+morphine	B-Chemical
+with	O
+metamizol	B-Chemical
+resulted	O
+in	O
+a	O
+markedly	O
+antinociceptive	O
+potentiation	O
+and	O
+an	O
+increasing	O
+of	O
+the	O
+duration	O
+of	O
+action	O
+after	O
+a	O
+single	O
+(	O
+298	O
++	O
+/	O
+-	O
+7	O
+vs	O
+.	O
+139	O
++	O
+/	O
+-	O
+36	O
+units	O
+area	O
+(	O
+ua	O
+)	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+repeated	O
+administration	O
+(	O
+280	O
++	O
+/	O
+-	O
+17	O
+vs	O
+.	O
+131	O
++	O
+/	O
+-	O
+22	O
+ua	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Antinociceptive	O
+effect	O
+of	O
+morphine	B-Chemical
+was	O
+reduced	O
+in	O
+chronically	O
+treated	O
+rats	O
+(	O
+39	O
++	O
+/	O
+-	O
+10	O
+vs	O
+.	O
+18	O
++	O
+/	O
+-	O
+5	O
+au	O
+)	O
+while	O
+the	O
+combination	O
+-	O
+induced	O
+antinociception	O
+was	O
+remained	O
+similar	O
+as	O
+an	O
+acute	O
+treatment	O
+(	O
+298	O
++	O
+/	O
+-	O
+7	O
+vs	O
+.	O
+280	O
++	O
+/	O
+-	O
+17	O
+au	O
+)	O
+.	O
+
+Acute	O
+antinociceptive	O
+effects	O
+of	O
+the	O
+combination	O
+were	O
+partially	O
+prevented	O
+by	O
+3	O
+.	O
+2	O
+mg	O
+/	O
+kg	O
+naloxone	B-Chemical
+s	O
+.	O
+c	O
+.	O
+
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+suggesting	O
+the	O
+partial	O
+involvement	O
+of	O
+the	O
+opioidergic	O
+system	O
+in	O
+the	O
+synergism	O
+observed	O
+.	O
+
+In	O
+independent	O
+groups	O
+,	O
+morphine	B-Chemical
+inhibited	O
+the	O
+intestinal	O
+transit	O
+in	O
+48	O
++	O
+/	O
+-	O
+4	O
+%	O
+and	O
+38	O
++	O
+/	O
+-	O
+4	O
+%	O
+after	O
+acute	O
+and	O
+chronic	O
+treatment	O
+,	O
+respectively	O
+,	O
+suggesting	O
+that	O
+tolerance	O
+did	O
+not	O
+develop	O
+to	O
+the	O
+constipating	B-Disease
+effects	O
+.	O
+
+The	O
+combination	O
+inhibited	O
+intestinal	O
+transit	O
+similar	O
+to	O
+that	O
+produced	O
+by	O
+morphine	B-Chemical
+regardless	O
+of	O
+the	O
+time	O
+of	O
+treatment	O
+,	O
+suggesting	O
+that	O
+metamizol	B-Chemical
+did	O
+not	O
+potentiate	O
+morphine	B-Chemical
+-	O
+induced	O
+constipation	B-Disease
+.	O
+
+These	O
+findings	O
+show	O
+a	O
+significant	O
+interaction	O
+between	O
+morphine	B-Chemical
+and	O
+metamizol	B-Chemical
+in	O
+chronically	O
+treated	O
+rats	O
+,	O
+suggesting	O
+that	O
+this	O
+combination	O
+could	O
+be	O
+useful	O
+for	O
+the	O
+treatment	O
+of	O
+chronic	B-Disease
+pain	I-Disease
+.	O
+
+Ifosfamide	B-Chemical
+encephalopathy	B-Disease
+presenting	O
+with	O
+asterixis	B-Disease
+.	O
+
+CNS	O
+toxic	O
+effects	O
+of	O
+the	O
+antineoplastic	O
+agent	O
+ifosfamide	B-Chemical
+(	O
+IFX	B-Chemical
+)	O
+are	O
+frequent	O
+and	O
+include	O
+a	O
+variety	O
+of	O
+neurological	O
+symptoms	O
+that	O
+can	O
+limit	O
+drug	O
+use	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+a	O
+51	O
+-	O
+year	O
+-	O
+old	O
+man	O
+who	O
+developed	O
+severe	O
+,	O
+disabling	O
+negative	O
+myoclonus	B-Disease
+of	O
+the	O
+upper	O
+and	O
+lower	O
+extremities	O
+after	O
+the	O
+infusion	O
+of	O
+ifosfamide	B-Chemical
+for	O
+plasmacytoma	B-Disease
+.	O
+
+He	O
+was	O
+awake	O
+,	O
+revealed	O
+no	O
+changes	O
+of	O
+mental	O
+status	O
+and	O
+at	O
+rest	O
+there	O
+were	O
+no	O
+further	O
+motor	O
+symptoms	O
+.	O
+
+Cranial	O
+magnetic	O
+resonance	O
+imaging	O
+and	O
+extensive	O
+laboratory	O
+studies	O
+failed	O
+to	O
+reveal	O
+structural	B-Disease
+lesions	I-Disease
+of	I-Disease
+the	I-Disease
+brain	I-Disease
+and	O
+metabolic	B-Disease
+abnormalities	I-Disease
+.	O
+
+An	O
+electroencephalogram	O
+showed	O
+continuous	O
+,	O
+generalized	O
+irregular	O
+slowing	O
+with	O
+admixed	O
+periodic	O
+triphasic	O
+waves	O
+indicating	O
+symptomatic	O
+encephalopathy	B-Disease
+.	O
+
+The	O
+administration	O
+of	O
+ifosfamide	B-Chemical
+was	O
+discontinued	O
+and	O
+within	O
+12	O
+h	O
+the	O
+asterixis	B-Disease
+resolved	O
+completely	O
+.	O
+
+In	O
+the	O
+patient	O
+described	O
+,	O
+the	O
+presence	O
+of	O
+asterixis	B-Disease
+during	O
+infusion	O
+of	O
+ifosfamide	B-Chemical
+,	O
+normal	O
+laboratory	O
+findings	O
+and	O
+imaging	O
+studies	O
+and	O
+the	O
+resolution	O
+of	O
+symptoms	O
+following	O
+the	O
+discontinuation	O
+of	O
+the	O
+drug	O
+suggest	O
+that	O
+negative	O
+myoclonus	B-Disease
+is	O
+associated	O
+with	O
+the	O
+use	O
+of	O
+IFX	B-Chemical
+.	O
+
+Antagonism	O
+between	O
+interleukin	O
+3	O
+and	O
+erythropoietin	O
+in	O
+mice	O
+with	O
+azidothymidine	B-Chemical
+-	O
+induced	O
+anemia	B-Disease
+and	O
+in	O
+bone	O
+marrow	O
+endothelial	O
+cells	O
+.	O
+
+Azidothymidine	B-Chemical
+(	O
+AZT	B-Chemical
+)	O
+-	O
+induced	O
+anemia	B-Disease
+in	O
+mice	O
+can	O
+be	O
+reversed	O
+by	O
+the	O
+administration	O
+of	O
+IGF	O
+-	O
+IL	O
+-	O
+3	O
+(	O
+fusion	O
+protein	O
+of	O
+insulin	O
+-	O
+like	O
+growth	O
+factor	O
+II	O
+(	O
+IGF	O
+II	O
+)	O
+and	O
+interleukin	O
+3	O
+)	O
+.	O
+
+Although	O
+interleukin	O
+3	O
+(	O
+IL	O
+-	O
+3	O
+)	O
+and	O
+erythropoietin	O
+(	O
+EPO	O
+)	O
+are	O
+known	O
+to	O
+act	O
+synergistically	O
+on	O
+hematopoietic	O
+cell	O
+proliferation	O
+in	O
+vitro	O
+,	O
+injection	O
+of	O
+IGF	O
+-	O
+IL	O
+-	O
+3	O
+and	O
+EPO	O
+in	O
+AZT	B-Chemical
+-	O
+treated	O
+mice	O
+resulted	O
+in	O
+a	O
+reduction	O
+of	O
+red	O
+cells	O
+and	O
+an	O
+increase	O
+of	O
+plasma	O
+EPO	O
+levels	O
+as	O
+compared	O
+to	O
+animals	O
+treated	O
+with	O
+IGF	O
+-	O
+IL	O
+-	O
+3	O
+or	O
+EPO	O
+alone	O
+.	O
+
+We	O
+tested	O
+the	O
+hypothesis	O
+that	O
+the	O
+antagonistic	O
+effect	O
+of	O
+IL	O
+-	O
+3	O
+and	O
+EPO	O
+on	O
+erythroid	O
+cells	O
+may	O
+be	O
+mediated	O
+by	O
+endothelial	O
+cells	O
+.	O
+
+Bovine	O
+liver	O
+erythroid	O
+cells	O
+were	O
+cultured	O
+on	O
+monolayers	O
+of	O
+human	O
+bone	O
+marrow	O
+endothelial	O
+cells	O
+previously	O
+treated	O
+with	O
+EPO	O
+and	O
+IGF	O
+-	O
+IL	O
+-	O
+3	O
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+reduction	O
+of	O
+thymidine	B-Chemical
+incorporation	O
+into	O
+both	O
+erythroid	O
+and	O
+endothelial	O
+cells	O
+in	O
+cultures	O
+pre	O
+-	O
+treated	O
+with	O
+IGF	O
+-	O
+IL	O
+-	O
+3	O
+and	O
+EPO	O
+.	O
+
+Endothelial	O
+cell	O
+culture	O
+supernatants	O
+separated	O
+by	O
+ultrafiltration	O
+and	O
+ultracentrifugation	O
+from	O
+cells	O
+treated	O
+with	O
+EPO	O
+and	O
+IL	O
+-	O
+3	O
+significantly	O
+reduced	O
+thymidine	B-Chemical
+incorporation	O
+into	O
+erythroid	O
+cells	O
+as	O
+compared	O
+to	O
+identical	O
+fractions	O
+obtained	O
+from	O
+the	O
+media	O
+of	O
+cells	O
+cultured	O
+with	O
+EPO	O
+alone	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+endothelial	O
+cells	O
+treated	O
+simultaneously	O
+with	O
+EPO	O
+and	O
+IL	O
+-	O
+3	O
+have	O
+a	O
+negative	O
+effect	O
+on	O
+erythroid	O
+cell	O
+production	O
+.	O
+
+The	O
+relationship	O
+between	O
+hippocampal	O
+acetylcholine	B-Chemical
+release	O
+and	O
+cholinergic	O
+convulsant	O
+sensitivity	O
+in	O
+withdrawal	O
+seizure	B-Disease
+-	O
+prone	O
+and	O
+withdrawal	O
+seizure	B-Disease
+-	O
+resistant	O
+selected	O
+mouse	O
+lines	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+septo	O
+-	O
+hippocampal	O
+cholinergic	O
+pathway	O
+has	O
+been	O
+implicated	O
+in	O
+epileptogenesis	O
+,	O
+and	O
+genetic	O
+factors	O
+influence	O
+the	O
+response	O
+to	O
+cholinergic	O
+agents	O
+,	O
+but	O
+limited	O
+data	O
+are	O
+available	O
+on	O
+cholinergic	O
+involvement	O
+in	O
+alcohol	B-Chemical
+withdrawal	O
+severity	O
+.	O
+
+Thus	O
+,	O
+the	O
+relationship	O
+between	O
+cholinergic	O
+activity	O
+and	O
+responsiveness	O
+and	O
+alcohol	B-Chemical
+withdrawal	O
+was	O
+investigated	O
+in	O
+a	O
+genetic	O
+animal	O
+model	O
+of	O
+ethanol	B-Chemical
+withdrawal	O
+severity	O
+.	O
+
+METHODS	O
+:	O
+Cholinergic	O
+convulsant	O
+sensitivity	O
+was	O
+examined	O
+in	O
+alcohol	B-Chemical
+-	O
+na	O
+ve	O
+Withdrawal	O
+Seizure	B-Disease
+-	O
+Prone	O
+(	O
+WSP	O
+)	O
+and	O
+-	O
+Resistant	O
+(	O
+WSR	O
+)	O
+mice	O
+.	O
+
+Animals	O
+were	O
+administered	O
+nicotine	B-Chemical
+,	O
+carbachol	B-Chemical
+,	O
+or	O
+neostigmine	B-Chemical
+via	O
+timed	O
+tail	O
+vein	O
+infusion	O
+,	O
+and	O
+the	O
+latencies	O
+to	O
+onset	O
+of	O
+tremor	B-Disease
+and	O
+clonus	O
+were	O
+recorded	O
+and	O
+converted	O
+to	O
+threshold	O
+dose	O
+.	O
+
+We	O
+also	O
+used	O
+microdialysis	O
+to	O
+measure	O
+basal	O
+and	O
+potassium	B-Chemical
+-	O
+stimulated	O
+acetylcholine	B-Chemical
+(	O
+ACh	B-Chemical
+)	O
+release	O
+in	O
+the	O
+CA1	O
+region	O
+of	O
+the	O
+hippocampus	O
+.	O
+
+Potassium	B-Chemical
+was	O
+applied	O
+by	O
+reverse	O
+dialysis	O
+twice	O
+,	O
+separated	O
+by	O
+75	O
+min	O
+.	O
+
+Hippocampal	O
+ACh	B-Chemical
+also	O
+was	O
+measured	O
+during	O
+testing	O
+for	O
+handling	O
+-	O
+induced	O
+convulsions	B-Disease
+.	O
+
+RESULTS	O
+:	O
+Sensitivity	O
+to	O
+several	O
+convulsion	B-Disease
+endpoints	O
+induced	O
+by	O
+nicotine	B-Chemical
+,	O
+carbachol	B-Chemical
+,	O
+and	O
+neostigmine	B-Chemical
+were	O
+significantly	O
+greater	O
+in	O
+WSR	O
+versus	O
+WSP	O
+mice	O
+.	O
+
+In	O
+microdialysis	O
+experiments	O
+,	O
+the	O
+lines	O
+did	O
+not	O
+differ	O
+in	O
+basal	O
+release	O
+of	O
+ACh	B-Chemical
+,	O
+and	O
+50	O
+mM	O
+KCl	B-Chemical
+increased	O
+ACh	B-Chemical
+output	O
+in	O
+both	O
+lines	O
+of	O
+mice	O
+.	O
+
+However	O
+,	O
+the	O
+increase	O
+in	O
+release	O
+of	O
+ACh	B-Chemical
+produced	O
+by	O
+the	O
+first	O
+application	O
+of	O
+KCl	B-Chemical
+was	O
+2	O
+-	O
+fold	O
+higher	O
+in	O
+WSP	O
+versus	O
+WSR	O
+mice	O
+.	O
+
+When	O
+hippocampal	O
+ACh	B-Chemical
+was	O
+measured	O
+during	O
+testing	O
+for	O
+handling	O
+-	O
+induced	O
+convulsions	B-Disease
+,	O
+extracellular	O
+ACh	B-Chemical
+was	O
+significantly	O
+elevated	O
+(	O
+192	O
+%	O
+)	O
+in	O
+WSP	O
+mice	O
+,	O
+but	O
+was	O
+nonsignificantly	O
+elevated	O
+(	O
+59	O
+%	O
+)	O
+in	O
+WSR	O
+mice	O
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+results	O
+suggest	O
+that	O
+differences	O
+in	O
+cholinergic	O
+activity	O
+and	O
+postsynaptic	O
+sensitivity	O
+to	O
+cholinergic	O
+convulsants	B-Disease
+may	O
+be	O
+associated	O
+with	O
+ethanol	B-Chemical
+withdrawal	O
+severity	O
+and	O
+implicate	O
+cholinergic	O
+mechanisms	O
+in	O
+alcohol	B-Chemical
+withdrawal	O
+.	O
+
+Specifically	O
+,	O
+WSP	O
+mice	O
+may	O
+have	O
+lower	O
+sensitivity	O
+to	O
+cholinergic	O
+convulsants	B-Disease
+compared	O
+with	O
+WSR	O
+because	O
+of	O
+postsynaptic	O
+receptor	O
+desensitization	O
+brought	O
+on	O
+by	O
+higher	O
+activity	O
+of	O
+cholinergic	O
+neurons	O
+.	O
+
+Capsaicin	B-Chemical
+-	O
+induced	O
+muscle	B-Disease
+pain	I-Disease
+alters	O
+the	O
+excitability	O
+of	O
+the	O
+human	O
+jaw	O
+-	O
+stretch	O
+reflex	O
+.	O
+
+The	O
+pathophysiology	O
+of	O
+painful	O
+temporomandibular	B-Disease
+disorders	I-Disease
+is	O
+not	O
+fully	O
+understood	O
+,	O
+but	O
+evidence	O
+suggests	O
+that	O
+muscle	B-Disease
+pain	I-Disease
+modulates	O
+motor	O
+function	O
+in	O
+characteristic	O
+ways	O
+.	O
+
+This	O
+study	O
+tested	O
+the	O
+hypothesis	O
+that	O
+activation	O
+of	O
+nociceptive	B-Disease
+muscle	I-Disease
+afferent	O
+fibers	O
+would	O
+be	O
+linked	O
+to	O
+an	O
+increased	O
+excitability	O
+of	O
+the	O
+human	O
+jaw	O
+-	O
+stretch	O
+reflex	O
+and	O
+whether	O
+this	O
+process	O
+would	O
+be	O
+sensitive	O
+to	O
+length	O
+and	O
+velocity	O
+of	O
+the	O
+stretch	O
+.	O
+
+Capsaicin	B-Chemical
+(	O
+10	O
+micro	O
+g	O
+)	O
+was	O
+injected	O
+into	O
+the	O
+masseter	O
+muscle	O
+to	O
+induce	O
+pain	B-Disease
+in	O
+11	O
+healthy	O
+volunteers	O
+.	O
+
+Short	O
+-	O
+latency	O
+reflex	O
+responses	O
+were	O
+evoked	O
+in	O
+the	O
+masseter	O
+and	O
+temporalis	O
+muscles	O
+by	O
+a	O
+stretch	O
+device	O
+with	O
+different	O
+velocities	O
+and	O
+displacements	O
+before	O
+,	O
+during	O
+,	O
+and	O
+after	O
+the	O
+pain	B-Disease
+.	O
+
+The	O
+normalized	O
+reflex	O
+amplitude	O
+increased	O
+with	O
+an	O
+increase	O
+in	O
+velocity	O
+at	O
+a	O
+given	O
+displacement	O
+,	O
+but	O
+remained	O
+constant	O
+with	O
+different	O
+displacements	O
+at	O
+a	O
+given	O
+velocity	O
+.	O
+
+The	O
+normalized	O
+reflex	O
+amplitude	O
+was	O
+significantly	O
+higher	O
+during	O
+pain	B-Disease
+,	O
+but	O
+only	O
+at	O
+faster	O
+stretches	O
+in	O
+the	O
+painful	B-Disease
+muscle	I-Disease
+.	O
+
+Increased	O
+sensitivity	O
+of	O
+the	O
+fusimotor	O
+system	O
+during	O
+acute	O
+muscle	B-Disease
+pain	I-Disease
+could	O
+be	O
+one	O
+likely	O
+mechanism	O
+to	O
+explain	O
+the	O
+findings	O
+.	O
+
+Effects	O
+of	O
+5	O
+-	O
+HT1B	O
+receptor	O
+ligands	O
+microinjected	O
+into	O
+the	O
+accumbal	O
+shell	O
+or	O
+core	O
+on	O
+the	O
+cocaine	B-Chemical
+-	O
+induced	O
+locomotor	B-Disease
+hyperactivity	I-Disease
+in	O
+rats	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+examine	O
+the	O
+effect	O
+of	O
+5	O
+-	O
+HT1B	O
+receptor	O
+ligands	O
+microinjected	O
+into	O
+the	O
+subregions	O
+of	O
+the	O
+nucleus	O
+accumbens	O
+(	O
+the	O
+shell	O
+and	O
+the	O
+core	O
+)	O
+on	O
+the	O
+locomotor	B-Disease
+hyperactivity	I-Disease
+induced	O
+by	O
+cocaine	B-Chemical
+in	O
+rats	O
+.	O
+
+Male	O
+Wistar	O
+rats	O
+were	O
+implanted	O
+bilaterally	O
+with	O
+cannulae	O
+into	O
+the	O
+accumbens	O
+shell	O
+or	O
+core	O
+,	O
+and	O
+then	O
+were	O
+locally	O
+injected	O
+with	O
+GR	B-Chemical
+55562	I-Chemical
+(	O
+an	O
+antagonist	O
+of	O
+5	O
+-	O
+HT1B	O
+receptors	O
+)	O
+or	O
+CP	B-Chemical
+93129	I-Chemical
+(	O
+an	O
+agonist	O
+of	O
+5	O
+-	O
+HT1B	O
+receptors	O
+)	O
+.	O
+
+Given	O
+alone	O
+to	O
+any	O
+accumbal	O
+subregion	O
+,	O
+GR	B-Chemical
+55562	I-Chemical
+(	O
+0	O
+.	O
+1	O
+-	O
+10	O
+microg	O
+/	O
+side	O
+)	O
+or	O
+CP	B-Chemical
+93129	I-Chemical
+(	O
+0	O
+.	O
+1	O
+-	O
+10	O
+microg	O
+/	O
+side	O
+)	O
+did	O
+not	O
+change	O
+basal	O
+locomotor	O
+activity	O
+.	O
+
+Systemic	O
+cocaine	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+significantly	O
+increased	O
+the	O
+locomotor	O
+activity	O
+of	O
+rats	O
+.	O
+
+GR	B-Chemical
+55562	I-Chemical
+(	O
+0	O
+.	O
+1	O
+-	O
+10	O
+microg	O
+/	O
+side	O
+)	O
+,	O
+administered	O
+intra	O
+-	O
+accumbens	O
+shell	O
+prior	O
+to	O
+cocaine	B-Chemical
+,	O
+dose	O
+-	O
+dependently	O
+attenuated	O
+the	O
+psychostimulant	O
+-	O
+induced	O
+locomotor	B-Disease
+hyperactivity	I-Disease
+.	O
+
+Such	O
+attenuation	O
+was	O
+not	O
+found	O
+in	O
+animals	O
+which	O
+had	O
+been	O
+injected	O
+with	O
+GR	B-Chemical
+55562	I-Chemical
+into	O
+the	O
+accumbens	O
+core	O
+.	O
+
+When	O
+injected	O
+into	O
+the	O
+accumbens	O
+shell	O
+(	O
+but	O
+not	O
+the	O
+core	O
+)	O
+before	O
+cocaine	B-Chemical
+,	O
+CP	B-Chemical
+93129	I-Chemical
+(	O
+0	O
+.	O
+1	O
+-	O
+10	O
+microg	O
+/	O
+side	O
+)	O
+enhanced	O
+the	O
+locomotor	O
+response	O
+to	O
+cocaine	B-Chemical
+;	O
+the	O
+maximum	O
+effect	O
+being	O
+observed	O
+after	O
+10	O
+microg	O
+/	O
+side	O
+of	O
+the	O
+agonist	O
+.	O
+
+The	O
+later	O
+enhancement	O
+was	O
+attenuated	O
+after	O
+intra	O
+-	O
+accumbens	O
+shell	O
+treatment	O
+with	O
+GR	B-Chemical
+55562	I-Chemical
+(	O
+1	O
+microg	O
+/	O
+side	O
+)	O
+.	O
+
+Our	O
+findings	O
+indicate	O
+that	O
+cocaine	B-Chemical
+induced	O
+hyperlocomotion	B-Disease
+is	O
+modified	O
+by	O
+5	O
+-	O
+HT1B	O
+receptor	O
+ligands	O
+microinjected	O
+into	O
+the	O
+accumbens	O
+shell	O
+,	O
+but	O
+not	O
+core	O
+,	O
+this	O
+modification	O
+consisting	O
+in	O
+inhibitory	O
+and	O
+facilitatory	O
+effects	O
+of	O
+the	O
+5	O
+-	O
+HT1B	O
+receptor	O
+antagonist	O
+(	O
+GR	B-Chemical
+55562	I-Chemical
+)	O
+and	O
+agonist	O
+(	O
+CP	B-Chemical
+93129	I-Chemical
+)	O
+,	O
+respectively	O
+.	O
+
+In	O
+other	O
+words	O
+,	O
+the	O
+present	O
+results	O
+suggest	O
+that	O
+the	O
+accumbal	O
+shell	O
+5	O
+-	O
+HT1B	O
+receptors	O
+play	O
+a	O
+permissive	O
+role	O
+in	O
+the	O
+behavioural	O
+response	O
+to	O
+the	O
+psychostimulant	O
+.	O
+
+Cocaine	B-Chemical
+related	O
+chest	B-Disease
+pain	I-Disease
+:	O
+are	O
+we	O
+seeing	O
+the	O
+tip	O
+of	O
+an	O
+iceberg	O
+?	O
+
+The	O
+recreational	O
+use	O
+of	O
+cocaine	B-Chemical
+is	O
+on	O
+the	O
+increase	O
+.	O
+
+The	O
+emergency	O
+nurse	O
+ought	O
+to	O
+be	O
+familiar	O
+with	O
+some	O
+of	O
+the	O
+cardiovascular	O
+consequences	O
+of	O
+cocaine	B-Chemical
+use	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+tendency	O
+of	O
+cocaine	B-Chemical
+to	O
+produce	O
+chest	B-Disease
+pain	I-Disease
+ought	O
+to	O
+be	O
+in	O
+the	O
+mind	O
+of	O
+the	O
+emergency	O
+nurse	O
+when	O
+faced	O
+with	O
+a	O
+young	O
+victim	O
+of	O
+chest	B-Disease
+pain	I-Disease
+who	O
+is	O
+otherwise	O
+at	O
+low	O
+risk	O
+.	O
+
+The	O
+mechanism	O
+of	O
+chest	B-Disease
+pain	I-Disease
+related	O
+to	O
+cocaine	B-Chemical
+use	O
+is	O
+discussed	O
+and	O
+treatment	O
+dilemmas	O
+are	O
+discussed	O
+.	O
+
+Finally	O
+,	O
+moral	O
+issues	O
+relating	O
+to	O
+the	O
+testing	O
+of	O
+potential	O
+cocaine	B-Chemical
+users	O
+will	O
+be	O
+addressed	O
+.	O
+
+Crossover	O
+comparison	O
+of	O
+efficacy	O
+and	O
+preference	O
+for	O
+rizatriptan	B-Chemical
+10	O
+mg	O
+versus	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+in	O
+migraine	B-Disease
+.	O
+
+Rizatriptan	B-Chemical
+is	O
+a	O
+selective	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+(	O
+1B	O
+/	O
+1D	O
+)	O
+receptor	O
+agonist	O
+with	O
+rapid	O
+oral	O
+absorption	O
+and	O
+early	O
+onset	O
+of	O
+action	O
+in	O
+the	O
+acute	O
+treatment	O
+of	O
+migraine	B-Disease
+.	O
+
+This	O
+randomized	O
+double	O
+-	O
+blind	O
+crossover	O
+outpatient	O
+study	O
+assessed	O
+the	O
+preference	O
+for	O
+1	O
+rizatriptan	B-Chemical
+10	O
+mg	O
+tablet	O
+to	O
+2	O
+ergotamine	B-Chemical
+1	O
+mg	O
+/	O
+caffeine	B-Chemical
+100	O
+mg	O
+tablets	O
+in	O
+439	O
+patients	O
+treating	O
+a	O
+single	O
+migraine	B-Disease
+attack	O
+with	O
+each	O
+therapy	O
+.	O
+
+Of	O
+patients	O
+expressing	O
+a	O
+preference	O
+(	O
+89	O
+.	O
+1	O
+%	O
+)	O
+,	O
+more	O
+than	O
+twice	O
+as	O
+many	O
+preferred	O
+rizatriptan	B-Chemical
+to	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+(	O
+69	O
+.	O
+9	O
+vs	O
+.	O
+30	O
+.	O
+1	O
+%	O
+,	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Faster	O
+relief	O
+of	O
+headache	B-Disease
+was	O
+the	O
+most	O
+important	O
+reason	O
+for	O
+preference	O
+,	O
+cited	O
+by	O
+67	O
+.	O
+3	O
+%	O
+of	O
+patients	O
+preferring	O
+rizatriptan	B-Chemical
+and	O
+54	O
+.	O
+2	O
+%	O
+of	O
+patients	O
+who	O
+preferred	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+.	O
+
+The	O
+co	O
+-	O
+primary	O
+endpoint	O
+of	O
+being	O
+pain	B-Disease
+free	O
+at	O
+2	O
+h	O
+was	O
+also	O
+in	O
+favor	O
+of	O
+rizatriptan	B-Chemical
+.	O
+
+Forty	O
+-	O
+nine	O
+percent	O
+of	O
+patients	O
+were	O
+pain	B-Disease
+free	O
+2	O
+h	O
+after	O
+rizatriptan	B-Chemical
+,	O
+compared	O
+with	O
+24	O
+.	O
+3	O
+%	O
+treated	O
+with	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+(	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+,	O
+rizatriptan	B-Chemical
+being	O
+superior	O
+within	O
+1	O
+h	O
+of	O
+treatment	O
+.	O
+
+Headache	B-Disease
+relief	O
+at	O
+2	O
+h	O
+was	O
+75	O
+.	O
+9	O
+%	O
+for	O
+rizatriptan	B-Chemical
+and	O
+47	O
+.	O
+3	O
+%	O
+for	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+(	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+,	O
+with	O
+rizatriptan	B-Chemical
+being	O
+superior	O
+to	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+within	O
+30	O
+min	O
+of	O
+dosing	O
+.	O
+
+Almost	O
+36	O
+%	O
+of	O
+patients	O
+taking	O
+rizatriptan	B-Chemical
+were	O
+pain	B-Disease
+free	O
+at	O
+2	O
+h	O
+and	O
+had	O
+no	O
+recurrence	O
+or	O
+need	O
+for	O
+additional	O
+medication	O
+within	O
+24	O
+h	O
+,	O
+compared	O
+to	O
+20	O
+%	O
+of	O
+patients	O
+on	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+(	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Rizatriptan	B-Chemical
+was	O
+also	O
+superior	O
+to	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+in	O
+the	O
+proportions	O
+of	O
+patients	O
+with	O
+no	O
+nausea	B-Disease
+,	O
+vomiting	B-Disease
+,	O
+phonophobia	B-Disease
+or	O
+photophobia	B-Disease
+and	O
+for	O
+patients	O
+with	O
+normal	O
+function	O
+2	O
+h	O
+after	O
+drug	O
+intake	O
+(	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+More	O
+patients	O
+were	O
+(	O
+completely	O
+,	O
+very	O
+or	O
+somewhat	O
+)	O
+satisfied	O
+2	O
+h	O
+after	O
+treatment	O
+with	O
+rizatriptan	B-Chemical
+(	O
+69	O
+.	O
+8	O
+%	O
+)	O
+than	O
+at	O
+2	O
+h	O
+after	O
+treatment	O
+with	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+(	O
+38	O
+.	O
+6	O
+%	O
+,	O
+p	O
+<	O
+or	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Recurrence	O
+rates	O
+were	O
+31	O
+.	O
+4	O
+%	O
+with	O
+rizatriptan	B-Chemical
+and	O
+15	O
+.	O
+3	O
+%	O
+with	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+.	O
+
+Both	O
+active	O
+treatments	O
+were	O
+well	O
+tolerated	O
+.	O
+
+The	O
+most	O
+common	O
+adverse	O
+events	O
+(	O
+incidence	O
+>	O
+or	O
+=	O
+5	O
+%	O
+in	O
+one	O
+group	O
+)	O
+after	O
+rizatriptan	B-Chemical
+and	O
+ergotamine	B-Chemical
+/	O
+caffeine	B-Chemical
+,	O
+respectively	O
+,	O
+were	O
+dizziness	B-Disease
+(	O
+6	O
+.	O
+7	O
+and	O
+5	O
+.	O
+3	O
+%	O
+)	O
+,	O
+nausea	B-Disease
+(	O
+4	O
+.	O
+2	O
+and	O
+8	O
+.	O
+5	O
+%	O
+)	O
+and	O
+somnolence	B-Disease
+(	O
+5	O
+.	O
+5	O
+and	O
+2	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+Severe	O
+ocular	B-Disease
+and	I-Disease
+orbital	I-Disease
+toxicity	I-Disease
+after	O
+intracarotid	O
+injection	O
+of	O
+carboplatin	B-Chemical
+for	O
+recurrent	O
+glioblastomas	B-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Glioblastoma	B-Disease
+is	O
+a	O
+malignant	B-Disease
+tumor	I-Disease
+that	O
+occurs	O
+in	O
+the	O
+cerebrum	O
+during	O
+adulthood	O
+.	O
+
+With	O
+current	O
+treatment	O
+regimens	O
+including	O
+combined	O
+surgery	O
+,	O
+radiation	O
+and	O
+chemotherapy	O
+,	O
+the	O
+average	O
+life	O
+expectancy	O
+of	O
+the	O
+patients	O
+is	O
+limited	O
+to	O
+approximately	O
+1	O
+year	O
+.	O
+
+Therefore	O
+,	O
+patients	O
+with	O
+glioblastoma	B-Disease
+sometimes	O
+have	O
+intracarotid	O
+injection	O
+of	O
+carcinostatics	O
+added	O
+to	O
+the	O
+treatment	O
+regimen	O
+.	O
+
+Generally	O
+,	O
+carboplatin	B-Chemical
+is	O
+said	O
+to	O
+have	O
+milder	O
+side	O
+effects	O
+than	O
+cisplatin	B-Chemical
+,	O
+whose	O
+ocular	B-Disease
+and	I-Disease
+orbital	I-Disease
+toxicity	I-Disease
+are	O
+well	O
+known	O
+.	O
+
+However	O
+,	O
+we	O
+experienced	O
+a	O
+case	O
+of	O
+severe	O
+ocular	B-Disease
+and	I-Disease
+orbital	I-Disease
+toxicity	I-Disease
+after	O
+intracarotid	O
+injection	O
+of	O
+carboplatin	B-Chemical
+,	O
+which	O
+is	O
+infrequently	O
+reported	O
+.	O
+
+CASE	O
+:	O
+A	O
+58	O
+-	O
+year	O
+-	O
+old	O
+man	O
+received	O
+an	O
+intracarotid	O
+injection	O
+of	O
+carboplatin	B-Chemical
+for	O
+recurrent	O
+glioblastomas	B-Disease
+in	O
+his	O
+left	O
+temporal	O
+lobe	O
+.	O
+
+He	O
+complained	O
+of	O
+pain	B-Disease
+and	I-Disease
+visual	I-Disease
+disturbance	I-Disease
+in	I-Disease
+the	I-Disease
+ipsilateral	I-Disease
+eye	I-Disease
+30	O
+h	O
+after	O
+the	O
+injection	O
+.	O
+
+Various	O
+ocular	O
+symptoms	O
+and	O
+findings	O
+caused	O
+by	O
+carboplatin	B-Chemical
+toxicity	B-Disease
+were	O
+seen	O
+.	O
+
+RESULTS	O
+:	O
+He	O
+was	O
+treated	O
+with	O
+intravenous	O
+administration	O
+of	O
+corticosteroids	O
+and	O
+glycerin	B-Chemical
+for	O
+6	O
+days	O
+after	O
+the	O
+injection	O
+.	O
+
+Although	O
+the	O
+intraocular	O
+pressure	O
+elevation	O
+caused	O
+by	O
+secondary	O
+acute	O
+angle	O
+-	O
+closure	O
+glaucoma	B-Disease
+decreased	O
+and	O
+ocular	B-Disease
+pain	I-Disease
+diminished	O
+,	O
+inexorable	O
+papilledema	B-Disease
+and	O
+exudative	O
+retinal	B-Disease
+detachment	I-Disease
+continued	O
+for	O
+3	O
+weeks	O
+.	O
+
+Finally	O
+,	O
+6	O
+weeks	O
+later	O
+,	O
+diffuse	O
+chorioretinal	B-Disease
+atrophy	I-Disease
+with	O
+optic	B-Disease
+atrophy	I-Disease
+occurred	O
+and	O
+the	O
+vision	O
+in	O
+his	O
+left	O
+eye	O
+was	O
+lost	O
+.	O
+
+CONCLUSION	O
+:	O
+When	O
+performing	O
+intracarotid	O
+injection	O
+of	O
+carboplatin	B-Chemical
+,	O
+we	O
+must	O
+be	O
+aware	O
+of	O
+its	O
+potentially	O
+blinding	O
+ocular	B-Disease
+toxicity	I-Disease
+.	O
+
+It	O
+is	O
+recommended	O
+that	O
+further	O
+studies	O
+and	O
+investigations	O
+are	O
+undertaken	O
+in	O
+the	O
+effort	O
+to	O
+minimize	O
+such	O
+severe	O
+side	O
+effects	O
+.	O
+
+Visual	B-Disease
+hallucinations	I-Disease
+associated	O
+with	O
+zonisamide	B-Chemical
+.	O
+
+Zonisamide	B-Chemical
+is	O
+a	O
+broad	O
+-	O
+spectrum	O
+antiepileptic	O
+drug	O
+used	O
+to	O
+treat	O
+various	O
+types	O
+of	O
+seizures	B-Disease
+.	O
+
+Although	O
+visual	B-Disease
+hallucinations	I-Disease
+have	O
+not	O
+been	O
+reported	O
+as	O
+an	O
+adverse	O
+effect	O
+of	O
+this	O
+agent	O
+,	O
+we	O
+describe	O
+three	O
+patients	O
+who	O
+experienced	O
+complex	O
+visual	B-Disease
+hallucinations	I-Disease
+and	O
+altered	O
+mental	O
+status	O
+after	O
+zonisamide	B-Chemical
+treatment	O
+was	O
+begun	O
+or	O
+its	O
+dosage	O
+increased	O
+.	O
+
+All	O
+three	O
+had	O
+been	O
+diagnosed	O
+earlier	O
+with	O
+epilepsy	B-Disease
+,	O
+and	O
+their	O
+electroencephalogram	O
+(	O
+EEG	O
+)	O
+findings	O
+were	O
+abnormal	O
+.	O
+
+During	O
+monitoring	O
+,	O
+visual	B-Disease
+hallucinations	I-Disease
+did	O
+not	O
+correlate	O
+with	O
+EEG	O
+readings	O
+,	O
+nor	O
+did	O
+video	O
+recording	O
+capture	O
+any	O
+of	O
+the	O
+described	O
+events	O
+.	O
+
+None	O
+of	O
+the	O
+patients	O
+had	O
+experienced	O
+visual	B-Disease
+hallucinations	I-Disease
+before	O
+this	O
+event	O
+.	O
+
+The	O
+only	O
+recent	O
+change	O
+in	O
+their	O
+treatment	O
+was	O
+the	O
+introduction	O
+or	O
+increased	O
+dosage	O
+of	O
+zonisamide	B-Chemical
+.	O
+
+With	O
+either	O
+discontinuation	O
+or	O
+decreased	O
+dosage	O
+of	O
+the	O
+drug	O
+the	O
+symptoms	O
+disappeared	O
+and	O
+did	O
+not	O
+recur	O
+.	O
+
+Further	O
+observations	O
+and	O
+reports	O
+will	O
+help	O
+clarify	O
+this	O
+adverse	O
+effect	O
+.	O
+
+Until	O
+then	O
+,	O
+clinicians	O
+need	O
+to	O
+be	O
+aware	O
+of	O
+this	O
+possible	O
+complication	O
+associated	O
+with	O
+zonisamide	B-Chemical
+.	O
+
+Anti	O
+-	O
+epileptic	B-Disease
+drugs	O
+-	O
+induced	O
+de	O
+novo	O
+absence	B-Disease
+seizures	I-Disease
+.	O
+
+The	O
+authors	O
+present	O
+three	O
+patients	O
+with	O
+de	O
+novo	O
+absence	B-Disease
+epilepsy	I-Disease
+after	O
+administration	O
+of	O
+carbamazepine	B-Chemical
+and	O
+vigabatrin	B-Chemical
+.	O
+
+Despite	O
+the	O
+underlying	O
+diseases	O
+,	O
+the	O
+prognosis	O
+for	O
+drug	O
+-	O
+induced	O
+de	O
+novo	O
+absence	B-Disease
+seizure	I-Disease
+is	O
+good	O
+because	O
+it	O
+subsides	O
+rapidly	O
+after	O
+discontinuing	O
+the	O
+use	O
+of	O
+the	O
+offending	O
+drugs	O
+.	O
+
+The	O
+gamma	B-Chemical
+-	I-Chemical
+aminobutyric	I-Chemical
+acid	I-Chemical
+-	O
+transmitted	O
+thalamocortical	O
+circuitry	O
+accounts	O
+for	O
+a	O
+major	O
+part	O
+of	O
+the	O
+underlying	O
+neurophysiology	O
+of	O
+the	O
+absence	B-Disease
+epilepsy	I-Disease
+.	O
+
+Because	O
+drug	O
+-	O
+induced	O
+de	O
+novo	O
+absence	B-Disease
+seizure	I-Disease
+is	O
+rare	O
+,	O
+pro	O
+-	O
+absence	O
+drugs	O
+can	O
+only	O
+be	O
+considered	O
+a	O
+promoting	O
+factor	O
+.	O
+
+The	O
+underlying	O
+epileptogenecity	O
+of	O
+the	O
+patients	O
+or	O
+the	O
+synergistic	O
+effects	O
+of	O
+the	O
+accompanying	O
+drugs	O
+is	O
+required	O
+to	O
+trigger	O
+the	O
+de	O
+novo	O
+absence	B-Disease
+seizure	I-Disease
+.	O
+
+The	O
+possibility	O
+of	O
+drug	O
+-	O
+induced	O
+aggravation	O
+should	O
+be	O
+considered	O
+whenever	O
+an	O
+unexpected	O
+increase	O
+in	O
+seizure	B-Disease
+frequency	O
+and	O
+/	O
+or	O
+new	O
+seizure	B-Disease
+types	O
+appear	O
+following	O
+a	O
+change	O
+in	O
+drug	O
+treatment	O
+.	O
+
+By	O
+understanding	O
+the	O
+underlying	O
+mechanism	O
+of	O
+absence	B-Disease
+epilepsy	I-Disease
+,	O
+we	O
+can	O
+avoid	O
+the	O
+inappropriate	O
+use	O
+of	O
+anticonvulsants	O
+in	O
+children	O
+with	O
+epilepsy	B-Disease
+and	O
+prevent	O
+drug	O
+-	O
+induced	O
+absence	B-Disease
+seizures	I-Disease
+.	O
+
+Prenatal	O
+dexamethasone	B-Chemical
+programs	O
+hypertension	B-Disease
+and	O
+renal	B-Disease
+injury	I-Disease
+in	O
+the	O
+rat	O
+.	O
+
+Dexamethasone	O
+is	O
+frequently	O
+administered	O
+to	O
+the	O
+developing	O
+fetus	O
+to	O
+accelerate	O
+pulmonary	O
+development	O
+.	O
+
+The	O
+purpose	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+determine	O
+if	O
+prenatal	O
+dexamethasone	B-Chemical
+programmed	O
+a	O
+progressive	O
+increase	B-Disease
+in	I-Disease
+blood	I-Disease
+pressure	I-Disease
+and	O
+renal	B-Disease
+injury	I-Disease
+in	O
+rats	O
+.	O
+
+Pregnant	O
+rats	O
+were	O
+given	O
+either	O
+vehicle	O
+or	O
+2	O
+daily	O
+intraperitoneal	O
+injections	O
+of	O
+dexamethasone	B-Chemical
+(	O
+0	O
+.	O
+2	O
+mg	O
+/	O
+kg	O
+body	O
+weight	O
+)	O
+on	O
+gestational	O
+days	O
+11	O
+and	O
+12	O
+,	O
+13	O
+and	O
+14	O
+,	O
+15	O
+and	O
+16	O
+,	O
+17	O
+and	O
+18	O
+,	O
+or	O
+19	O
+and	O
+20	O
+.	O
+
+Offspring	O
+of	O
+rats	O
+administered	O
+dexamethasone	B-Chemical
+on	O
+days	O
+15	O
+and	O
+16	O
+gestation	O
+had	O
+a	O
+20	O
+%	O
+reduction	B-Disease
+in	I-Disease
+glomerular	I-Disease
+number	I-Disease
+compared	O
+with	O
+control	O
+at	O
+6	O
+to	O
+9	O
+months	O
+of	O
+age	O
+(	O
+22	O
+527	O
++	O
+/	O
+-	O
+509	O
+versus	O
+28	O
+050	O
++	O
+/	O
+-	O
+561	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+which	O
+was	O
+comparable	O
+to	O
+the	O
+percent	O
+reduction	O
+in	O
+glomeruli	O
+measured	O
+at	O
+3	O
+weeks	O
+of	O
+age	O
+.	O
+
+Six	O
+-	O
+to	O
+9	O
+-	O
+month	O
+old	O
+rats	O
+receiving	O
+prenatal	O
+dexamethasone	B-Chemical
+on	O
+days	O
+17	O
+and	O
+18	O
+of	O
+gestation	O
+had	O
+a	O
+17	O
+%	O
+reduction	O
+in	O
+glomeruli	O
+(	O
+23	O
+380	O
++	O
+/	O
+-	O
+587	O
+)	O
+compared	O
+with	O
+control	O
+rats	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Male	O
+rats	O
+that	O
+received	O
+prenatal	O
+dexamethasone	B-Chemical
+on	O
+days	O
+15	O
+and	O
+16	O
+,	O
+17	O
+and	O
+18	O
+,	O
+and	O
+13	O
+and	O
+14	O
+of	O
+gestation	O
+had	O
+elevated	B-Disease
+blood	I-Disease
+pressures	I-Disease
+at	O
+6	O
+months	O
+of	O
+age	O
+;	O
+the	O
+latter	O
+group	O
+did	O
+not	O
+have	O
+a	O
+reduction	B-Disease
+in	I-Disease
+glomerular	I-Disease
+number	I-Disease
+.	O
+
+Adult	O
+rats	O
+given	O
+dexamethasone	B-Chemical
+on	O
+days	O
+15	O
+and	O
+16	O
+of	O
+gestation	O
+had	O
+more	O
+glomeruli	O
+with	O
+glomerulosclerosis	B-Disease
+than	O
+control	O
+rats	O
+.	O
+
+This	O
+study	O
+shows	O
+that	O
+prenatal	O
+dexamethasone	B-Chemical
+in	O
+rats	O
+results	O
+in	O
+a	O
+reduction	B-Disease
+in	I-Disease
+glomerular	I-Disease
+number	I-Disease
+,	O
+glomerulosclerosis	B-Disease
+,	O
+and	O
+hypertension	B-Disease
+when	O
+administered	O
+at	O
+specific	O
+points	O
+during	O
+gestation	O
+.	O
+
+Hypertension	B-Disease
+was	O
+observed	O
+in	O
+animals	O
+that	O
+had	O
+a	O
+reduction	O
+in	O
+glomeruli	O
+as	O
+well	O
+as	O
+in	O
+a	O
+group	O
+that	O
+did	O
+not	O
+have	O
+a	O
+reduction	B-Disease
+in	I-Disease
+glomerular	I-Disease
+number	I-Disease
+,	O
+suggesting	O
+that	O
+a	O
+reduction	B-Disease
+in	I-Disease
+glomerular	I-Disease
+number	I-Disease
+is	O
+not	O
+the	O
+sole	O
+cause	O
+for	O
+the	O
+development	O
+of	O
+hypertension	B-Disease
+.	O
+
+Kidney	O
+function	O
+and	O
+morphology	O
+after	O
+short	O
+-	O
+term	O
+combination	O
+therapy	O
+with	O
+cyclosporine	B-Chemical
+A	I-Chemical
+,	O
+tacrolimus	B-Chemical
+and	O
+sirolimus	B-Chemical
+in	O
+the	O
+rat	O
+.	O
+
+BACKGROUND	O
+:	O
+Sirolimus	B-Chemical
+(	O
+SRL	B-Chemical
+)	O
+may	O
+supplement	O
+calcineurin	O
+inhibitors	O
+in	O
+clinical	O
+organ	O
+transplantation	O
+.	O
+
+These	O
+are	O
+nephrotoxic	B-Disease
+,	O
+but	O
+SRL	B-Chemical
+seems	O
+to	O
+act	O
+differently	O
+displaying	O
+only	O
+minor	O
+nephrotoxic	B-Disease
+effects	O
+,	O
+although	O
+this	O
+question	O
+is	O
+still	O
+open	O
+.	O
+
+In	O
+a	O
+number	O
+of	O
+treatment	O
+protocols	O
+where	O
+SRL	B-Chemical
+was	O
+combined	O
+with	O
+a	O
+calcineurin	O
+inhibitor	O
+indications	O
+of	O
+a	O
+synergistic	O
+nephrotoxic	B-Disease
+effect	O
+were	O
+described	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+examine	O
+further	O
+the	O
+renal	O
+function	O
+,	O
+including	O
+morphological	O
+analysis	O
+of	O
+the	O
+kidneys	O
+of	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+treated	O
+with	O
+either	O
+cyclosporine	B-Chemical
+A	I-Chemical
+(	O
+CsA	B-Chemical
+)	O
+,	O
+tacrolimus	B-Chemical
+(	O
+FK506	B-Chemical
+)	O
+or	O
+SRL	B-Chemical
+as	O
+monotherapies	O
+or	O
+in	O
+different	O
+combinations	O
+.	O
+
+METHODS	O
+:	O
+For	O
+a	O
+period	O
+of	O
+2	O
+weeks	O
+,	O
+CsA	B-Chemical
+15	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+(	O
+given	O
+orally	O
+)	O
+,	O
+FK506	B-Chemical
+3	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+(	O
+given	O
+orally	O
+)	O
+or	O
+SRL	B-Chemical
+0	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+(	O
+given	O
+intraperitoneally	O
+)	O
+was	O
+administered	O
+once	O
+a	O
+day	O
+as	O
+these	O
+doses	O
+have	O
+earlier	O
+been	O
+found	O
+to	O
+achieve	O
+a	O
+significant	O
+immunosuppressive	O
+effect	O
+in	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+.	O
+
+In	O
+the	O
+'	O
+conscious	O
+catheterized	O
+rat	O
+'	O
+model	O
+,	O
+the	O
+glomerular	O
+filtration	O
+rate	O
+(	O
+GFR	O
+)	O
+was	O
+measured	O
+as	O
+the	O
+clearance	O
+of	O
+Cr	O
+(	O
+EDTA	O
+)	O
+.	O
+
+The	O
+morphological	O
+analysis	O
+of	O
+the	O
+kidneys	O
+included	O
+a	O
+semi	O
+-	O
+quantitative	O
+scoring	O
+system	O
+analysing	O
+the	O
+degree	O
+of	O
+striped	O
+fibrosis	B-Disease
+,	O
+subcapsular	O
+fibrosis	B-Disease
+and	O
+the	O
+number	O
+of	O
+basophilic	O
+tubules	O
+,	O
+plus	O
+an	O
+additional	O
+stereological	O
+analysis	O
+of	O
+the	O
+total	O
+grade	O
+of	O
+fibrosis	B-Disease
+in	O
+the	O
+cortex	O
+stained	O
+with	O
+Sirius	O
+Red	O
+.	O
+
+RESULTS	O
+:	O
+CsA	B-Chemical
+,	O
+FK506	B-Chemical
+and	O
+SRL	B-Chemical
+all	O
+significantly	O
+decreased	O
+the	O
+GFR	O
+.	O
+
+A	O
+further	O
+deterioration	O
+was	O
+seen	O
+when	O
+CsA	B-Chemical
+was	O
+combined	O
+with	O
+either	O
+FK506	B-Chemical
+or	O
+SRL	B-Chemical
+,	O
+whereas	O
+the	O
+GFR	O
+remained	O
+unchanged	O
+in	O
+the	O
+group	O
+treated	O
+with	O
+FK506	B-Chemical
+plus	O
+SRL	B-Chemical
+when	O
+compared	O
+with	O
+treatment	O
+with	O
+any	O
+of	O
+the	O
+single	O
+substances	O
+.	O
+
+The	O
+morphological	O
+changes	O
+presented	O
+a	O
+similar	O
+pattern	O
+.	O
+
+The	O
+semi	O
+-	O
+quantitative	O
+scoring	O
+was	O
+significantly	O
+worst	O
+in	O
+the	O
+group	O
+treated	O
+with	O
+CsA	B-Chemical
+plus	O
+SRL	B-Chemical
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+compared	O
+with	O
+controls	O
+)	O
+and	O
+the	O
+analysis	O
+of	O
+the	O
+total	O
+grade	O
+of	O
+fibrosis	B-Disease
+also	O
+showed	O
+the	O
+highest	O
+proportion	O
+in	O
+the	O
+same	O
+group	O
+and	O
+was	O
+significantly	O
+different	O
+from	O
+controls	O
+(	O
+P	O
+<	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+The	O
+FK506	B-Chemical
+plus	O
+SRL	B-Chemical
+combination	O
+showed	O
+only	O
+a	O
+marginally	O
+higher	O
+degree	O
+of	O
+fibrosis	B-Disease
+as	O
+compared	O
+with	O
+controls	O
+(	O
+P	O
+=	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+rat	O
+study	O
+demonstrated	O
+a	O
+synergistic	O
+nephrotoxic	B-Disease
+effect	O
+of	O
+CsA	B-Chemical
+plus	O
+SRL	B-Chemical
+,	O
+whereas	O
+FK506	B-Chemical
+plus	O
+SRL	B-Chemical
+was	O
+better	O
+tolerated	O
+.	O
+
+Evaluation	O
+of	O
+cardiac	O
+troponin	O
+I	O
+and	O
+T	O
+levels	O
+as	O
+markers	O
+of	O
+myocardial	B-Disease
+damage	I-Disease
+in	O
+doxorubicin	B-Chemical
+-	O
+induced	O
+cardiomyopathy	B-Disease
+rats	O
+,	O
+and	O
+their	O
+relationship	O
+with	O
+echocardiographic	O
+and	O
+histological	O
+findings	O
+.	O
+
+BACKGROUND	O
+:	O
+Cardiac	O
+troponins	O
+I	O
+(	O
+cTnI	O
+)	O
+and	O
+T	O
+(	O
+cTnT	O
+)	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+highly	O
+sensitive	O
+and	O
+specific	O
+markers	O
+of	O
+myocardial	B-Disease
+cell	I-Disease
+injury	I-Disease
+.	O
+
+We	O
+investigated	O
+the	O
+diagnostic	O
+value	O
+of	O
+cTnI	O
+and	O
+cTnT	O
+for	O
+the	O
+diagnosis	O
+of	O
+myocardial	B-Disease
+damage	I-Disease
+in	O
+a	O
+rat	O
+model	O
+of	O
+doxorubicin	B-Chemical
+(	O
+DOX	B-Chemical
+)	O
+-	O
+induced	O
+cardiomyopathy	B-Disease
+,	O
+and	O
+we	O
+examined	O
+the	O
+relationship	O
+between	O
+serial	O
+cTnI	O
+and	O
+cTnT	O
+with	O
+the	O
+development	O
+of	O
+cardiac	B-Disease
+disorders	I-Disease
+monitored	O
+by	O
+echocardiography	O
+and	O
+histological	O
+examinations	O
+in	O
+this	O
+model	O
+.	O
+
+METHODS	O
+:	O
+Thirty	O
+-	O
+five	O
+Wistar	O
+rats	O
+were	O
+given	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+DOX	B-Chemical
+,	O
+i	O
+.	O
+v	O
+.	O
+,	O
+weekly	O
+for	O
+up	O
+to	O
+8	O
+weeks	O
+for	O
+a	O
+total	O
+cumulative	O
+dose	O
+of	O
+12	O
+mg	O
+/	O
+kg	O
+BW	O
+.	O
+
+Ten	O
+rats	O
+received	O
+saline	O
+as	O
+a	O
+control	O
+group	O
+.	O
+
+cTnI	O
+was	O
+measured	O
+with	O
+Access	O
+(	O
+R	O
+)	O
+(	O
+ng	O
+/	O
+ml	O
+)	O
+and	O
+a	O
+research	O
+immunoassay	O
+(	O
+pg	O
+/	O
+ml	O
+)	O
+,	O
+and	O
+compared	O
+with	O
+cTnT	O
+,	O
+CK	O
+-	O
+MB	O
+mass	O
+and	O
+CK	O
+.	O
+
+By	O
+using	O
+transthoracic	O
+echocardiography	O
+,	O
+anterior	O
+and	O
+posterior	O
+wall	O
+thickness	O
+,	O
+LV	O
+diameters	O
+and	O
+LV	O
+fractional	O
+shortening	O
+(	O
+FS	O
+)	O
+were	O
+measured	O
+in	O
+all	O
+rats	O
+before	O
+DOX	B-Chemical
+or	O
+saline	O
+,	O
+and	O
+at	O
+weeks	O
+6	O
+and	O
+9	O
+after	O
+treatment	O
+in	O
+all	O
+surviving	O
+rats	O
+.	O
+
+Histology	O
+was	O
+performed	O
+in	O
+DOX	B-Chemical
+-	O
+rats	O
+at	O
+6	O
+and	O
+9	O
+weeks	O
+after	O
+the	O
+last	O
+DOX	B-Chemical
+dose	O
+and	O
+in	O
+all	O
+controls	O
+.	O
+
+RESULTS	O
+:	O
+Eighteen	O
+of	O
+the	O
+DOX	B-Chemical
+rats	O
+died	O
+prematurely	O
+of	O
+general	O
+toxicity	B-Disease
+during	O
+the	O
+9	O
+-	O
+week	O
+period	O
+.	O
+
+End	O
+-	O
+diastolic	O
+(	O
+ED	O
+)	O
+and	O
+end	O
+-	O
+systolic	O
+(	O
+ES	O
+)	O
+LV	O
+diameters	O
+/	O
+BW	O
+significantly	O
+increased	O
+,	O
+whereas	O
+LV	O
+FS	O
+was	O
+decreased	O
+after	O
+9	O
+weeks	O
+in	O
+the	O
+DOX	B-Chemical
+group	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+These	O
+parameters	O
+remained	O
+unchanged	O
+in	O
+controls	O
+.	O
+
+Histological	O
+evaluation	O
+of	O
+hearts	O
+from	O
+all	O
+rats	O
+given	O
+DOX	B-Chemical
+revealed	O
+significant	O
+slight	O
+degrees	O
+of	O
+perivascular	O
+and	O
+interstitial	O
+fibrosis	B-Disease
+.	O
+
+In	O
+7	O
+of	O
+the	O
+18	O
+rats	O
+,	O
+degeneration	O
+and	O
+myocyte	O
+vacuolisation	O
+were	O
+found	O
+.	O
+
+Only	O
+five	O
+of	O
+the	O
+controls	O
+exhibited	O
+evidence	O
+of	O
+very	O
+slight	O
+perivascular	O
+fibrosis	B-Disease
+.	O
+
+A	O
+significant	O
+rise	O
+in	O
+cTnT	O
+was	O
+found	O
+in	O
+DOX	B-Chemical
+rats	O
+after	O
+cumulative	O
+doses	O
+of	O
+7	O
+.	O
+5	O
+and	O
+12	O
+mg	O
+/	O
+kg	O
+in	O
+comparison	O
+with	O
+baseline	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+cTnT	O
+found	O
+in	O
+rats	O
+after	O
+12	O
+mg	O
+/	O
+kg	O
+were	O
+significantly	O
+greater	O
+than	O
+that	O
+found	O
+after	O
+7	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+DOX	B-Chemical
+.	O
+
+Maximal	O
+cTnI	O
+(	O
+pg	O
+/	O
+ml	O
+)	O
+and	O
+cTnT	O
+levels	O
+were	O
+significantly	O
+increased	O
+in	O
+DOX	B-Chemical
+rats	O
+compared	O
+with	O
+controls	O
+(	O
+p	O
+=	O
+0	O
+.	O
+006	O
+,	O
+0	O
+.	O
+007	O
+)	O
+.	O
+
+cTnI	O
+(	O
+ng	O
+/	O
+ml	O
+)	O
+,	O
+CK	O
+-	O
+MB	O
+mass	O
+and	O
+CK	O
+remained	O
+unchanged	O
+in	O
+DOX	B-Chemical
+rats	O
+compared	O
+with	O
+controls	O
+.	O
+
+All	O
+markers	O
+remained	O
+stable	O
+in	O
+controls	O
+.	O
+
+Analysis	O
+of	O
+data	O
+revealed	O
+a	O
+significant	O
+correlation	O
+between	O
+maximal	O
+cTnT	O
+and	O
+ED	O
+and	O
+ES	O
+LV	O
+diameters	O
+/	O
+BW	O
+(	O
+r	O
+=	O
+0	O
+.	O
+81	O
+and	O
+0	O
+.	O
+65	O
+;	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+A	O
+significant	O
+relationship	O
+was	O
+observed	O
+between	O
+maximal	O
+cTnT	O
+and	O
+the	O
+extent	O
+of	O
+myocardial	O
+morphological	O
+changes	O
+,	O
+and	O
+between	O
+LV	O
+diameters	O
+/	O
+BW	O
+and	O
+histological	O
+findings	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Among	O
+markers	O
+of	O
+ischemic	B-Disease
+injury	I-Disease
+after	O
+DOX	B-Chemical
+in	O
+rats	O
+,	O
+cTnT	O
+showed	O
+the	O
+greatest	O
+ability	O
+to	O
+detect	O
+myocardial	B-Disease
+damage	I-Disease
+assessed	O
+by	O
+echocardiographic	O
+detection	O
+and	O
+histological	O
+changes	O
+.	O
+
+Although	O
+there	O
+was	O
+a	O
+discrepancy	O
+between	O
+the	O
+amount	O
+of	O
+cTnI	O
+and	O
+cTnT	O
+after	O
+DOX	B-Chemical
+,	O
+probably	O
+due	O
+to	O
+heterogeneity	O
+in	O
+cross	O
+-	O
+reactivities	O
+of	O
+mAbs	O
+to	O
+various	O
+cTnI	O
+and	O
+cTnT	O
+forms	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+cTnT	O
+in	O
+rats	O
+after	O
+DOX	B-Chemical
+indicates	O
+cell	O
+damage	O
+determined	O
+by	O
+the	O
+magnitude	O
+of	O
+injury	O
+induced	O
+and	O
+that	O
+cTnT	O
+should	O
+be	O
+a	O
+useful	O
+marker	O
+for	O
+the	O
+prediction	O
+of	O
+experimentally	O
+induced	O
+cardiotoxicity	B-Disease
+and	O
+possibly	O
+for	O
+cardioprotective	O
+experiments	O
+.	O
+
+Octreotide	B-Chemical
+-	O
+induced	O
+hypoxemia	B-Disease
+and	O
+pulmonary	B-Disease
+hypertension	I-Disease
+in	O
+premature	O
+neonates	O
+.	O
+
+The	O
+authors	O
+report	O
+2	O
+cases	O
+of	O
+premature	O
+neonates	O
+who	O
+had	O
+enterocutaneous	O
+fistula	B-Disease
+complicating	O
+necrotizing	B-Disease
+enterocolitis	I-Disease
+.	O
+
+Pulmonary	B-Disease
+hypertension	I-Disease
+developed	O
+after	O
+administration	O
+of	O
+a	O
+somatostatin	O
+analogue	O
+,	O
+octreotide	B-Chemical
+,	O
+to	O
+enhance	O
+resolution	O
+of	O
+the	O
+fistula	B-Disease
+.	O
+
+The	O
+authors	O
+discuss	O
+the	O
+mechanism	O
+of	O
+the	O
+occurrence	O
+of	O
+this	O
+complication	O
+and	O
+recommend	O
+caution	O
+of	O
+its	O
+use	O
+in	O
+high	O
+-	O
+risk	O
+premature	O
+neonates	O
+.	O
+
+The	O
+risk	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+in	O
+women	O
+prescribed	O
+cyproterone	B-Chemical
+acetate	I-Chemical
+in	O
+combination	O
+with	O
+ethinyl	B-Chemical
+estradiol	I-Chemical
+:	O
+a	O
+nested	O
+cohort	O
+analysis	O
+and	O
+case	O
+-	O
+control	O
+study	O
+.	O
+
+BACKGROUND	O
+:	O
+Cyproterone	B-Chemical
+acetate	I-Chemical
+combined	O
+with	O
+ethinyl	B-Chemical
+estradiol	I-Chemical
+(	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+)	O
+is	O
+licensed	O
+in	O
+the	O
+UK	O
+for	O
+the	O
+treatment	O
+of	O
+women	O
+with	O
+acne	B-Disease
+and	O
+hirsutism	B-Disease
+and	O
+is	O
+also	O
+a	O
+treatment	O
+option	O
+for	O
+polycystic	B-Disease
+ovary	I-Disease
+syndrome	I-Disease
+(	O
+PCOS	B-Disease
+)	O
+.	O
+
+Previous	O
+studies	O
+have	O
+demonstrated	O
+an	O
+increased	O
+risk	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+(	O
+VTE	B-Disease
+)	O
+associated	O
+with	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+compared	O
+with	O
+conventional	O
+combined	O
+oral	B-Chemical
+contraceptives	I-Chemical
+(	O
+COCs	O
+)	O
+.	O
+
+We	O
+believe	O
+the	O
+results	O
+of	O
+those	O
+studies	O
+may	O
+have	O
+been	O
+affected	O
+by	O
+residual	O
+confounding	O
+.	O
+
+METHODS	O
+:	O
+Using	O
+the	O
+General	O
+Practice	O
+Research	O
+Database	O
+we	O
+conducted	O
+a	O
+cohort	O
+analysis	O
+and	O
+case	O
+-	O
+control	O
+study	O
+nested	O
+within	O
+a	O
+population	O
+of	O
+women	O
+aged	O
+between	O
+15	O
+and	O
+39	O
+years	O
+with	O
+acne	B-Disease
+,	O
+hirsutism	B-Disease
+or	O
+PCOS	B-Disease
+to	O
+estimate	O
+the	O
+risk	O
+of	O
+VTE	B-Disease
+associated	O
+with	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+.	O
+
+RESULTS	O
+:	O
+The	O
+age	O
+-	O
+adjusted	O
+incidence	O
+rate	O
+ratio	O
+for	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+versus	O
+conventional	O
+COCs	O
+was	O
+2	O
+.	O
+20	O
+[	O
+95	O
+%	O
+confidence	O
+interval	O
+(	O
+CI	O
+)	O
+1	O
+.	O
+35	O
+-	O
+3	O
+.	O
+58	O
+]	O
+.	O
+
+Using	O
+as	O
+the	O
+reference	O
+group	O
+women	O
+who	O
+were	O
+not	O
+using	O
+oral	O
+contraception	O
+,	O
+had	O
+no	O
+recent	O
+pregnancy	O
+or	O
+menopausal	O
+symptoms	O
+,	O
+the	O
+case	O
+-	O
+control	O
+analysis	O
+gave	O
+an	O
+adjusted	O
+odds	O
+ratio	O
+(	O
+OR	O
+(	O
+adj	O
+)	O
+)	O
+of	O
+7	O
+.	O
+44	O
+(	O
+95	O
+%	O
+CI	O
+3	O
+.	O
+67	O
+-	O
+15	O
+.	O
+08	O
+)	O
+for	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+use	O
+compared	O
+with	O
+an	O
+OR	O
+(	O
+adj	O
+)	O
+of	O
+2	O
+.	O
+58	O
+(	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+60	O
+-	O
+4	O
+.	O
+18	O
+)	O
+for	O
+use	O
+of	O
+conventional	O
+COCs	O
+.	O
+
+CONCLUSIONS	O
+:	O
+We	O
+have	O
+demonstrated	O
+an	O
+increased	O
+risk	O
+of	O
+VTE	B-Disease
+associated	O
+with	O
+the	O
+use	O
+of	O
+CPA	B-Chemical
+/	O
+EE	B-Chemical
+in	O
+women	O
+with	O
+acne	B-Disease
+,	O
+hirsutism	B-Disease
+or	O
+PCOS	B-Disease
+although	O
+residual	O
+confounding	O
+by	O
+indication	O
+cannot	O
+be	O
+excluded	O
+.	O
+
+The	O
+effect	O
+of	O
+treatment	O
+with	O
+gum	B-Chemical
+Arabic	I-Chemical
+on	O
+gentamicin	B-Chemical
+nephrotoxicity	B-Disease
+in	O
+rats	O
+:	O
+a	O
+preliminary	O
+study	O
+.	O
+
+In	O
+the	O
+present	O
+work	O
+we	O
+assessed	O
+the	O
+effect	O
+of	O
+treatment	O
+of	O
+rats	O
+with	O
+gum	B-Chemical
+Arabic	I-Chemical
+on	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+induced	O
+by	O
+gentamicin	B-Chemical
+(	O
+GM	B-Chemical
+)	O
+nephrotoxicity	B-Disease
+.	O
+
+Rats	O
+were	O
+treated	O
+with	O
+the	O
+vehicle	O
+(	O
+2	O
+mL	O
+/	O
+kg	O
+of	O
+distilled	O
+water	O
+and	O
+5	O
+%	O
+w	O
+/	O
+v	O
+cellulose	O
+,	O
+10	O
+days	O
+)	O
+,	O
+gum	B-Chemical
+Arabic	I-Chemical
+(	O
+2	O
+mL	O
+/	O
+kg	O
+of	O
+a	O
+10	O
+%	O
+w	O
+/	O
+v	O
+aqueous	O
+suspension	O
+of	O
+gum	B-Chemical
+Arabic	I-Chemical
+powder	O
+,	O
+orally	O
+for	O
+10	O
+days	O
+)	O
+,	O
+or	O
+gum	B-Chemical
+Arabic	I-Chemical
+concomitantly	O
+with	O
+GM	B-Chemical
+(	O
+80mg	O
+/	O
+kg	O
+/	O
+day	O
+intramuscularly	O
+,	O
+during	O
+the	O
+last	O
+six	O
+days	O
+of	O
+the	O
+treatment	O
+period	O
+)	O
+.	O
+
+Nephrotoxicity	B-Disease
+was	O
+assessed	O
+by	O
+measuring	O
+the	O
+concentrations	O
+of	O
+creatinine	B-Chemical
+and	O
+urea	B-Chemical
+in	O
+the	O
+plasma	O
+and	O
+reduced	O
+glutathione	B-Chemical
+(	O
+GSH	B-Chemical
+)	O
+in	O
+the	O
+kidney	O
+cortex	O
+,	O
+and	O
+by	O
+light	O
+microscopic	O
+examination	O
+of	O
+kidney	O
+sections	O
+.	O
+
+The	O
+results	O
+indicated	O
+that	O
+concomitant	O
+treatment	O
+with	O
+gum	B-Chemical
+Arabic	I-Chemical
+and	O
+GM	B-Chemical
+significantly	O
+increased	O
+creatinine	B-Chemical
+and	O
+urea	B-Chemical
+by	O
+about	O
+183	O
+and	O
+239	O
+%	O
+,	O
+respectively	O
+(	O
+compared	O
+to	O
+432	O
+and	O
+346	O
+%	O
+,	O
+respectively	O
+,	O
+in	O
+rats	O
+treated	O
+with	O
+cellulose	O
+and	O
+GM	B-Chemical
+)	O
+,	O
+and	O
+decreased	O
+that	O
+of	O
+cortical	O
+GSH	B-Chemical
+by	O
+21	O
+%	O
+(	O
+compared	O
+to	O
+27	O
+%	O
+in	O
+the	O
+cellulose	O
+plus	O
+GM	B-Chemical
+group	O
+)	O
+The	O
+GM	B-Chemical
+-	O
+induced	O
+proximal	O
+tubular	B-Disease
+necrosis	I-Disease
+appeared	O
+to	O
+be	O
+slightly	O
+less	O
+severe	O
+in	O
+rats	O
+given	O
+GM	B-Chemical
+together	O
+with	O
+gum	B-Chemical
+Arabic	I-Chemical
+than	O
+in	O
+those	O
+given	O
+GM	B-Chemical
+and	O
+cellulose	O
+.	O
+
+It	O
+could	O
+be	O
+inferred	O
+that	O
+gum	B-Chemical
+Arabic	I-Chemical
+treatment	O
+has	O
+induced	O
+a	O
+modest	O
+amelioration	O
+of	O
+some	O
+of	O
+the	O
+histological	O
+and	O
+biochemical	O
+indices	O
+of	O
+GM	B-Chemical
+nephrotoxicity	B-Disease
+.	O
+
+Further	O
+work	O
+is	O
+warranted	O
+on	O
+the	O
+effect	O
+of	O
+the	O
+treatments	O
+on	O
+renal	O
+functional	O
+aspects	O
+in	O
+models	O
+of	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+,	O
+and	O
+on	O
+the	O
+mechanism	O
+(	O
+s	O
+)	O
+involved	O
+.	O
+
+Increased	O
+frequency	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+with	O
+the	O
+combination	O
+of	O
+docetaxel	B-Chemical
+and	O
+thalidomide	B-Chemical
+in	O
+patients	O
+with	O
+metastatic	O
+androgen	O
+-	O
+independent	O
+prostate	B-Disease
+cancer	I-Disease
+.	O
+
+STUDY	O
+OBJECTIVE	O
+:	O
+To	O
+evaluate	O
+the	O
+frequency	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+(	O
+VTE	B-Disease
+)	O
+in	O
+patients	O
+with	O
+advanced	O
+androgen	O
+-	O
+independent	O
+prostate	B-Disease
+cancer	I-Disease
+who	O
+were	O
+treated	O
+with	O
+docetaxel	B-Chemical
+alone	O
+or	O
+in	O
+combination	O
+with	O
+thalidomide	B-Chemical
+.	O
+
+DESIGN	O
+:	O
+Retrospective	O
+analysis	O
+of	O
+a	O
+randomized	O
+phase	O
+II	O
+trial	O
+.	O
+
+SETTING	O
+:	O
+National	O
+Institutes	O
+of	O
+Health	O
+clinical	O
+research	O
+center	O
+.	O
+
+PATIENTS	O
+:	O
+Seventy	O
+men	O
+,	O
+aged	O
+50	O
+-	O
+80	O
+years	O
+,	O
+with	O
+advanced	O
+androgen	O
+-	O
+independent	O
+prostate	B-Disease
+cancer	I-Disease
+.	O
+
+INTERVENTION	O
+:	O
+Each	O
+patient	O
+received	O
+either	O
+intravenous	O
+docetaxel	B-Chemical
+30	O
+mg	O
+/	O
+m2	O
+/	O
+week	O
+for	O
+3	O
+consecutive	O
+weeks	O
+,	O
+followed	O
+by	O
+1	O
+week	O
+off	O
+,	O
+or	O
+the	O
+combination	O
+of	O
+continuous	O
+oral	O
+thalidomide	B-Chemical
+200	O
+mg	O
+every	O
+evening	O
+plus	O
+the	O
+same	O
+docetaxel	B-Chemical
+regimen	O
+.	O
+
+This	O
+4	O
+-	O
+week	O
+cycle	O
+was	O
+repeated	O
+until	O
+there	O
+was	O
+evidence	O
+of	O
+excessive	O
+toxicity	B-Disease
+or	O
+disease	O
+progression	O
+.	O
+
+MEASUREMENTS	O
+AND	O
+MAIN	O
+RESULTS	O
+:	O
+None	O
+of	O
+23	O
+patients	O
+who	O
+received	O
+docetaxel	B-Chemical
+alone	O
+developed	O
+VTE	B-Disease
+,	O
+whereas	O
+9	O
+of	O
+47	O
+patients	O
+(	O
+19	O
+%	O
+)	O
+who	O
+received	O
+docetaxel	B-Chemical
+plus	O
+thalidomide	B-Chemical
+developed	O
+VTE	B-Disease
+(	O
+p	O
+=	O
+0	O
+.	O
+025	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+addition	O
+of	O
+thalidomide	B-Chemical
+to	O
+docetaxel	B-Chemical
+in	O
+the	O
+treatment	O
+of	O
+prostate	B-Disease
+cancer	I-Disease
+significantly	O
+increases	O
+the	O
+frequency	O
+of	O
+VTE	B-Disease
+.	O
+
+Clinicians	O
+should	O
+be	O
+aware	O
+of	O
+this	O
+potential	O
+complication	O
+when	O
+adding	O
+thalidomide	B-Chemical
+to	O
+chemotherapeutic	O
+regimens	O
+.	O
+
+Ticlopidine	B-Chemical
+-	O
+induced	O
+cholestatic	B-Disease
+hepatitis	I-Disease
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+report	O
+2	O
+cases	O
+of	O
+ticlopidine	B-Chemical
+-	O
+induced	O
+cholestatic	B-Disease
+hepatitis	I-Disease
+,	O
+investigate	O
+its	O
+mechanism	O
+,	O
+and	O
+compare	O
+the	O
+observed	O
+main	O
+characteristics	O
+with	O
+those	O
+of	O
+the	O
+published	O
+cases	O
+.	O
+
+CASE	O
+SUMMARIES	O
+:	O
+Two	O
+patients	O
+developed	O
+prolonged	O
+cholestatic	B-Disease
+hepatitis	I-Disease
+after	O
+receiving	O
+ticlopidine	B-Chemical
+following	O
+percutaneous	O
+coronary	O
+angioplasty	O
+,	O
+with	O
+complete	O
+remission	O
+during	O
+the	O
+follow	O
+-	O
+up	O
+period	O
+.	O
+
+T	O
+-	O
+cell	O
+stimulation	O
+by	O
+therapeutic	O
+concentration	O
+of	O
+ticlopidine	B-Chemical
+was	O
+demonstrated	O
+in	O
+vitro	O
+in	O
+the	O
+patients	O
+,	O
+but	O
+not	O
+in	O
+healthy	O
+controls	O
+.	O
+
+DISCUSSION	O
+:	O
+Cholestatic	B-Disease
+hepatitis	I-Disease
+is	O
+a	O
+rare	O
+complication	O
+of	O
+the	O
+antiplatelet	O
+agent	O
+ticlopidine	B-Chemical
+;	O
+several	O
+cases	O
+have	O
+been	O
+reported	O
+but	O
+few	O
+in	O
+the	O
+English	O
+literature	O
+.	O
+
+Our	O
+patients	O
+developed	O
+jaundice	B-Disease
+following	O
+treatment	O
+with	O
+ticlopidine	B-Chemical
+and	O
+showed	O
+the	O
+clinical	O
+and	O
+laboratory	O
+characteristics	O
+of	O
+cholestatic	B-Disease
+hepatitis	I-Disease
+,	O
+which	O
+resolved	O
+after	O
+discontinuation	O
+of	O
+the	O
+drug	O
+.	O
+
+Hepatitis	B-Disease
+may	O
+develop	O
+weeks	O
+after	O
+discontinuation	O
+of	O
+the	O
+drug	O
+and	O
+may	O
+run	O
+a	O
+prolonged	O
+course	O
+,	O
+but	O
+complete	O
+remission	O
+was	O
+observed	O
+in	O
+all	O
+reported	O
+cases	O
+.	O
+
+An	O
+objective	O
+causality	O
+assessment	O
+revealed	O
+that	O
+the	O
+adverse	O
+drug	O
+event	O
+was	O
+probably	O
+related	O
+to	O
+the	O
+use	O
+of	O
+ticlopidine	B-Chemical
+.	O
+
+The	O
+mechanisms	O
+of	O
+this	O
+ticlopidine	B-Chemical
+-	O
+induced	O
+cholestasis	B-Disease
+are	O
+unclear	O
+.	O
+
+Immune	O
+mechanisms	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+drug	O
+'	O
+s	O
+hepatotoxicity	B-Disease
+,	O
+as	O
+suggested	O
+by	O
+the	O
+T	O
+-	O
+cell	O
+stimulation	O
+study	O
+reported	O
+here	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Cholestatic	B-Disease
+hepatitis	I-Disease
+is	O
+a	O
+rare	O
+adverse	O
+effect	O
+of	O
+ticlopidine	B-Chemical
+that	O
+may	O
+be	O
+immune	O
+mediated	O
+.	O
+
+Patients	O
+receiving	O
+the	O
+drug	O
+should	O
+be	O
+monitored	O
+with	O
+liver	O
+function	O
+tests	O
+along	O
+with	O
+complete	O
+blood	O
+cell	O
+counts	O
+.	O
+
+This	O
+complication	O
+will	O
+be	O
+observed	O
+even	O
+less	O
+often	O
+in	O
+the	O
+future	O
+as	O
+ticlopidine	B-Chemical
+is	O
+being	O
+replaced	O
+by	O
+the	O
+newer	O
+antiplatelet	O
+agent	O
+clopidogrel	B-Chemical
+.	O
+
+Epithelial	O
+sodium	B-Chemical
+channel	O
+(	O
+ENaC	O
+)	O
+subunit	O
+mRNA	O
+and	O
+protein	O
+expression	O
+in	O
+rats	O
+with	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+-	O
+induced	O
+nephrotic	B-Disease
+syndrome	I-Disease
+.	O
+
+In	O
+experimental	O
+nephrotic	B-Disease
+syndrome	I-Disease
+,	O
+urinary	O
+sodium	B-Chemical
+excretion	O
+is	O
+decreased	O
+during	O
+the	O
+early	O
+phase	O
+of	O
+the	O
+disease	O
+.	O
+
+The	O
+molecular	O
+mechanism	O
+(	O
+s	O
+)	O
+leading	O
+to	O
+salt	O
+retention	O
+has	O
+not	O
+been	O
+completely	O
+elucidated	O
+.	O
+
+The	O
+rate	O
+-	O
+limiting	O
+constituent	O
+of	O
+collecting	O
+duct	O
+sodium	B-Chemical
+transport	O
+is	O
+the	O
+epithelial	O
+sodium	B-Chemical
+channel	O
+(	O
+ENaC	O
+)	O
+.	O
+
+We	O
+examined	O
+the	O
+abundance	O
+of	O
+ENaC	O
+subunit	O
+mRNAs	O
+and	O
+proteins	O
+in	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+(	O
+PAN	B-Chemical
+)	O
+-	O
+induced	O
+nephrotic	B-Disease
+syndrome	I-Disease
+.	O
+
+The	O
+time	O
+courses	O
+of	O
+urinary	O
+sodium	B-Chemical
+excretion	O
+,	O
+plasma	O
+aldosterone	B-Chemical
+concentration	O
+and	O
+proteinuria	B-Disease
+were	O
+studied	O
+in	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+treated	O
+with	O
+a	O
+single	O
+dose	O
+of	O
+either	O
+PAN	B-Chemical
+or	O
+vehicle	O
+.	O
+
+The	O
+relative	O
+amounts	O
+of	O
+alphaENaC	O
+,	O
+betaENaC	O
+and	O
+gammaENaC	O
+mRNAs	O
+were	O
+determined	O
+in	O
+kidneys	O
+from	O
+these	O
+rats	O
+by	O
+real	O
+-	O
+time	O
+quantitative	O
+TaqMan	O
+PCR	O
+,	O
+and	O
+the	O
+amounts	O
+of	O
+proteins	O
+by	O
+Western	O
+blot	O
+.	O
+
+The	O
+kinetics	O
+of	O
+urinary	O
+sodium	B-Chemical
+excretion	O
+and	O
+the	O
+appearance	O
+of	O
+proteinuria	B-Disease
+were	O
+comparable	O
+with	O
+those	O
+reported	O
+previously	O
+.	O
+
+Sodium	B-Chemical
+retention	O
+occurred	O
+on	O
+days	O
+2	O
+,	O
+3	O
+and	O
+6	O
+after	O
+PAN	B-Chemical
+injection	O
+.	O
+
+A	O
+significant	O
+up	O
+-	O
+regulation	O
+of	O
+alphaENaC	O
+and	O
+betaENaC	O
+mRNA	O
+abundance	O
+on	O
+days	O
+1	O
+and	O
+2	O
+preceded	O
+sodium	B-Chemical
+retention	O
+on	O
+days	O
+2	O
+and	O
+3	O
+.	O
+
+Conversely	O
+,	O
+down	O
+-	O
+regulation	O
+of	O
+alphaENaC	O
+,	O
+betaENaC	O
+and	O
+gammaENaC	O
+mRNA	O
+expression	O
+on	O
+day	O
+3	O
+occurred	O
+in	O
+the	O
+presence	O
+of	O
+high	O
+aldosterone	B-Chemical
+concentrations	O
+,	O
+and	O
+was	O
+followed	O
+by	O
+a	O
+return	O
+of	O
+sodium	B-Chemical
+excretion	O
+to	O
+control	O
+values	O
+.	O
+
+The	O
+amounts	O
+of	O
+alphaENaC	O
+,	O
+betaENaC	O
+and	O
+gammaENaC	O
+proteins	O
+were	O
+not	O
+increased	O
+during	O
+PAN	B-Chemical
+-	O
+induced	O
+sodium	B-Chemical
+retention	O
+.	O
+
+In	O
+conclusion	O
+,	O
+ENaC	O
+mRNA	O
+expression	O
+,	O
+especially	O
+alphaENaC	O
+,	O
+is	O
+increased	O
+in	O
+the	O
+very	O
+early	O
+phase	O
+of	O
+the	O
+experimental	O
+model	O
+of	O
+PAN	B-Chemical
+-	O
+induced	O
+nephrotic	B-Disease
+syndrome	I-Disease
+in	O
+rats	O
+,	O
+but	O
+appears	O
+to	O
+escape	O
+from	O
+the	O
+regulation	O
+by	O
+aldosterone	B-Chemical
+after	O
+day	O
+3	O
+.	O
+
+Sub	O
+-	O
+chronic	O
+low	O
+dose	O
+gamma	B-Chemical
+-	I-Chemical
+vinyl	I-Chemical
+GABA	I-Chemical
+(	O
+vigabatrin	B-Chemical
+)	O
+inhibits	O
+cocaine	B-Chemical
+-	O
+induced	O
+increases	O
+in	O
+nucleus	O
+accumbens	O
+dopamine	B-Chemical
+.	O
+
+RATIONALE	O
+:	O
+gamma	B-Chemical
+-	I-Chemical
+Vinyl	I-Chemical
+GABA	I-Chemical
+(	O
+GVG	B-Chemical
+)	O
+irreversibly	O
+inhibits	O
+GABA	B-Chemical
+-	O
+transaminase	O
+.	O
+
+This	O
+non	O
+-	O
+receptor	O
+mediated	O
+inhibition	O
+requires	O
+de	O
+novo	O
+synthesis	O
+for	O
+restoration	O
+of	O
+functional	O
+GABA	B-Chemical
+catabolism	O
+.	O
+
+OBJECTIVES	O
+:	O
+Given	O
+its	O
+preclinical	O
+success	O
+for	O
+treating	O
+substance	B-Disease
+abuse	I-Disease
+and	O
+the	O
+increased	O
+risk	O
+of	O
+visual	B-Disease
+field	I-Disease
+defects	I-Disease
+(	O
+VFD	B-Disease
+)	O
+associated	O
+with	O
+cumulative	O
+lifetime	O
+exposure	O
+,	O
+we	O
+explored	O
+the	O
+effects	O
+of	O
+sub	O
+-	O
+chronic	O
+low	O
+dose	O
+GVG	B-Chemical
+on	O
+cocaine	B-Chemical
+-	O
+induced	O
+increases	O
+in	O
+nucleus	O
+accumbens	O
+(	O
+NAcc	O
+)	O
+dopamine	B-Chemical
+(	O
+DA	B-Chemical
+)	O
+.	O
+
+METHODS	O
+:	O
+Using	O
+in	O
+vivo	O
+microdialysis	O
+,	O
+we	O
+compared	O
+acute	O
+exposure	O
+(	O
+450	O
+mg	O
+/	O
+kg	O
+)	O
+to	O
+an	O
+identical	O
+sub	O
+-	O
+chronic	O
+exposure	O
+(	O
+150	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+for	O
+3	O
+days	O
+)	O
+,	O
+followed	O
+by	O
+1	O
+-	O
+or	O
+3	O
+-	O
+day	O
+washout	O
+.	O
+
+Finally	O
+,	O
+we	O
+examined	O
+the	O
+low	O
+dose	O
+of	O
+150	O
+mg	O
+/	O
+kg	O
+(	O
+50	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+)	O
+using	O
+a	O
+similar	O
+washout	O
+period	O
+.	O
+
+RESULTS	O
+:	O
+Sub	O
+-	O
+chronic	O
+GVG	B-Chemical
+exposure	O
+inhibited	O
+the	O
+effect	O
+of	O
+cocaine	B-Chemical
+for	O
+3	O
+days	O
+,	O
+which	O
+exceeded	O
+in	O
+magnitude	O
+and	O
+duration	O
+the	O
+identical	O
+acute	O
+dose	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Sub	O
+-	O
+chronic	O
+low	O
+dose	O
+GVG	B-Chemical
+potentiates	O
+and	O
+extends	O
+the	O
+inhibition	O
+of	O
+cocaine	B-Chemical
+-	O
+induced	O
+increases	O
+in	O
+dopamine	B-Chemical
+,	O
+effectively	O
+reducing	O
+cumulative	O
+exposures	O
+and	O
+the	O
+risk	O
+for	O
+VFDS	O
+.	O
+
+MR	O
+imaging	O
+with	O
+quantitative	O
+diffusion	O
+mapping	O
+of	O
+tacrolimus	B-Chemical
+-	O
+induced	O
+neurotoxicity	B-Disease
+in	O
+organ	O
+transplant	O
+patients	O
+.	O
+
+Our	O
+objective	O
+was	O
+to	O
+investigate	O
+brain	O
+MR	O
+imaging	O
+findings	O
+and	O
+the	O
+utility	O
+of	O
+diffusion	O
+-	O
+weighted	O
+(	O
+DW	O
+)	O
+imaging	O
+in	O
+organ	O
+transplant	O
+patients	O
+who	O
+developed	O
+neurologic	O
+symptoms	O
+during	O
+tacrolimus	B-Chemical
+therapy	O
+.	O
+
+Brain	O
+MR	O
+studies	O
+,	O
+including	O
+DW	O
+imaging	O
+,	O
+were	O
+prospectively	O
+performed	O
+in	O
+14	O
+organ	O
+transplant	O
+patients	O
+receiving	O
+tacrolimus	B-Chemical
+who	O
+developed	O
+neurologic	B-Disease
+complications	I-Disease
+.	O
+
+In	O
+each	O
+patient	O
+who	O
+had	O
+abnormalities	O
+on	O
+the	O
+initial	O
+MR	O
+study	O
+,	O
+a	O
+follow	O
+-	O
+up	O
+MR	O
+study	O
+was	O
+performed	O
+1	O
+month	O
+later	O
+.	O
+
+Apparent	O
+diffusion	O
+coefficient	O
+(	O
+ADC	O
+)	O
+values	O
+on	O
+the	O
+initial	O
+MR	O
+study	O
+were	O
+correlated	O
+with	O
+reversibility	O
+of	O
+the	O
+lesions	O
+.	O
+
+Of	O
+the	O
+14	O
+patients	O
+,	O
+5	O
+(	O
+35	O
+.	O
+7	O
+%	O
+)	O
+had	O
+white	B-Disease
+matter	I-Disease
+abnormalities	I-Disease
+,	O
+1	O
+(	O
+7	O
+.	O
+1	O
+%	O
+)	O
+had	O
+putaminal	B-Disease
+hemorrhage	I-Disease
+,	O
+and	O
+8	O
+(	O
+57	O
+.	O
+1	O
+%	O
+)	O
+had	O
+normal	O
+findings	O
+on	O
+initial	O
+MR	O
+images	O
+.	O
+
+Among	O
+the	O
+5	O
+patients	O
+with	O
+white	B-Disease
+matter	I-Disease
+abnormalities	I-Disease
+,	O
+4	O
+patients	O
+(	O
+80	O
+.	O
+0	O
+%	O
+)	O
+showed	O
+higher	O
+than	O
+normal	O
+ADC	O
+values	O
+on	O
+initial	O
+MR	O
+images	O
+,	O
+and	O
+all	O
+showed	O
+complete	O
+resolution	O
+on	O
+follow	O
+-	O
+up	O
+images	O
+.	O
+
+The	O
+remaining	O
+1	O
+patient	O
+(	O
+20	O
+.	O
+0	O
+%	O
+)	O
+showed	O
+lower	O
+than	O
+normal	O
+ADC	O
+value	O
+and	O
+showed	O
+incomplete	O
+resolution	O
+with	O
+cortical	B-Disease
+laminar	I-Disease
+necrosis	I-Disease
+.	O
+
+Diffusion	O
+-	O
+weighted	O
+imaging	O
+may	O
+be	O
+useful	O
+in	O
+predicting	O
+the	O
+outcomes	O
+of	O
+the	O
+lesions	O
+of	O
+tacrolimus	B-Chemical
+-	O
+induced	O
+neurotoxicity	B-Disease
+.	O
+
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+transport	O
+in	O
+humans	O
+with	O
+cortisol	B-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+.	O
+
+A	O
+deficient	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+-	O
+nitric	B-Chemical
+oxide	I-Chemical
+system	O
+is	O
+implicated	O
+in	O
+cortisol	B-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+.	O
+
+We	O
+investigate	O
+whether	O
+abnormalities	O
+in	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+uptake	O
+contribute	O
+to	O
+this	O
+deficiency	O
+.	O
+
+Eight	O
+healthy	O
+men	O
+were	O
+recruited	O
+.	O
+
+Hydrocortisone	B-Chemical
+acetate	I-Chemical
+(	O
+50	O
+mg	O
+)	O
+was	O
+given	O
+orally	O
+every	O
+6	O
+hours	O
+for	O
+24	O
+hours	O
+after	O
+a	O
+5	O
+-	O
+day	O
+fixed	O
+-	O
+salt	O
+diet	O
+(	O
+150	O
+mmol	O
+/	O
+d	O
+)	O
+.	O
+
+Crossover	O
+studies	O
+were	O
+performed	O
+2	O
+weeks	O
+apart	O
+.	O
+
+Thirty	O
+milliliters	O
+of	O
+blood	O
+was	O
+obtained	O
+for	O
+isolation	O
+of	O
+peripheral	O
+blood	O
+mononuclear	O
+cells	O
+after	O
+each	O
+treatment	O
+period	O
+.	O
+
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+uptake	O
+was	O
+assessed	O
+in	O
+mononuclear	O
+cells	O
+incubated	O
+with	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+(	O
+1	O
+to	O
+300	O
+micromol	O
+/	O
+L	O
+)	O
+,	O
+incorporating	O
+100	O
+nmol	O
+/	O
+L	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+l	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+for	O
+a	O
+period	O
+of	O
+5	O
+minutes	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+Forearm	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+extraction	O
+was	O
+calculated	O
+after	O
+infusion	O
+of	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+into	O
+the	O
+brachial	O
+artery	O
+at	O
+a	O
+rate	O
+of	O
+100	O
+nCi	O
+/	O
+min	O
+for	O
+80	O
+minutes	O
+.	O
+
+Deep	O
+forearm	O
+venous	O
+samples	O
+were	O
+collected	O
+for	O
+determination	O
+of	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+extraction	O
+.	O
+
+Plasma	O
+cortisol	B-Chemical
+concentrations	O
+were	O
+significantly	O
+raised	O
+during	O
+the	O
+active	O
+phase	O
+(	O
+323	O
++	O
+/	O
+-	O
+43	O
+to	O
+1082	O
++	O
+/	O
+-	O
+245	O
+mmol	O
+/	O
+L	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Systolic	O
+blood	O
+pressure	O
+was	O
+elevated	O
+by	O
+an	O
+average	O
+of	O
+7	O
+mm	O
+Hg	O
+.	O
+
+Neither	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+transport	O
+into	O
+mononuclear	O
+cells	O
+(	O
+placebo	O
+vs	O
+active	O
+,	O
+26	O
+.	O
+3	O
++	O
+/	O
+-	O
+3	O
+.	O
+6	O
+vs	O
+29	O
+.	O
+0	O
++	O
+/	O
+-	O
+2	O
+.	O
+1	O
+pmol	O
+/	O
+10	O
+000	O
+cells	O
+per	O
+5	O
+minutes	O
+,	O
+respectively	O
+,	O
+at	O
+an	O
+l	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+concentration	O
+of	O
+300	O
+micromol	O
+/	O
+L	O
+)	O
+nor	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+extraction	O
+in	O
+the	O
+forearm	O
+(	O
+at	O
+80	O
+minutes	O
+,	O
+placebo	O
+vs	O
+active	O
+,	O
+1	O
+868	O
+904	O
++	O
+/	O
+-	O
+434	O
+962	O
+vs	O
+2	O
+013	O
+910	O
++	O
+/	O
+-	O
+770	O
+619	O
+disintegrations	O
+per	O
+minute	O
+)	O
+was	O
+affected	O
+by	O
+cortisol	B-Chemical
+treatment	O
+;	O
+ie	O
+,	O
+that	O
+L	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+uptake	O
+is	O
+not	O
+affected	O
+by	O
+short	O
+-	O
+term	O
+cortisol	B-Chemical
+treatment	O
+.	O
+
+We	O
+conclude	O
+that	O
+cortisol	B-Chemical
+-	O
+induced	O
+increases	B-Disease
+in	I-Disease
+blood	I-Disease
+pressure	I-Disease
+are	O
+not	O
+associated	O
+with	O
+abnormalities	O
+in	O
+the	O
+l	B-Chemical
+-	I-Chemical
+arginine	I-Chemical
+transport	O
+system	O
+.	O
+
+Amount	O
+of	O
+bleeding	B-Disease
+and	O
+hematoma	B-Disease
+size	O
+in	O
+the	O
+collagenase	O
+-	O
+induced	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+rat	O
+model	O
+.	O
+
+The	O
+aggravated	O
+risk	O
+on	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+(	O
+ICH	B-Disease
+)	O
+with	O
+drugs	O
+used	O
+for	O
+stroke	B-Disease
+patients	O
+should	O
+be	O
+estimated	O
+carefully	O
+.	O
+
+We	O
+therefore	O
+established	O
+sensitive	O
+quantification	O
+methods	O
+and	O
+provided	O
+a	O
+rat	O
+ICH	B-Disease
+model	O
+for	O
+detection	O
+of	O
+ICH	B-Disease
+deterioration	O
+.	O
+
+In	O
+ICH	B-Disease
+intrastriatally	O
+induced	O
+by	O
+0	O
+.	O
+014	O
+-	O
+unit	O
+,	O
+0	O
+.	O
+070	O
+-	O
+unit	O
+,	O
+and	O
+0	O
+.	O
+350	O
+-	O
+unit	O
+collagenase	O
+,	O
+the	O
+amount	O
+of	O
+bleeding	B-Disease
+was	O
+measured	O
+using	O
+a	O
+hemoglobin	O
+assay	O
+developed	O
+in	O
+the	O
+present	O
+study	O
+and	O
+was	O
+compared	O
+with	O
+the	O
+morphologically	O
+determined	O
+hematoma	B-Disease
+volume	O
+.	O
+
+The	O
+blood	O
+amounts	O
+and	O
+hematoma	B-Disease
+volumes	O
+were	O
+significantly	O
+correlated	O
+,	O
+and	O
+the	O
+hematoma	B-Disease
+induced	O
+by	O
+0	O
+.	O
+014	O
+-	O
+unit	O
+collagenase	O
+was	O
+adequate	O
+to	O
+detect	O
+ICH	B-Disease
+deterioration	O
+.	O
+
+In	O
+ICH	B-Disease
+induction	O
+using	O
+0	O
+.	O
+014	O
+-	O
+unit	O
+collagenase	O
+,	O
+heparin	B-Chemical
+enhanced	O
+the	O
+hematoma	B-Disease
+volume	O
+3	O
+.	O
+4	O
+-	O
+fold	O
+over	O
+that	O
+seen	O
+in	O
+control	O
+ICH	B-Disease
+animals	O
+and	O
+the	O
+bleeding	B-Disease
+7	O
+.	O
+6	O
+-	O
+fold	O
+.	O
+
+Data	O
+suggest	O
+that	O
+this	O
+sensitive	O
+hemoglobin	O
+assay	O
+is	O
+useful	O
+for	O
+ICH	B-Disease
+detection	O
+,	O
+and	O
+that	O
+a	O
+model	O
+with	O
+a	O
+small	O
+ICH	B-Disease
+induced	O
+with	O
+a	O
+low	O
+-	O
+dose	O
+collagenase	O
+should	O
+be	O
+used	O
+for	O
+evaluation	O
+of	O
+drugs	O
+that	O
+may	O
+affect	O
+ICH	B-Disease
+.	O
+
+Estradiol	B-Chemical
+reduces	O
+seizure	B-Disease
+-	O
+induced	O
+hippocampal	B-Disease
+injury	I-Disease
+in	O
+ovariectomized	O
+female	O
+but	O
+not	O
+in	O
+male	O
+rats	O
+.	O
+
+Estrogens	O
+protect	O
+ovariectomized	O
+rats	O
+from	O
+hippocampal	B-Disease
+injury	I-Disease
+induced	O
+by	O
+kainic	B-Chemical
+acid	I-Chemical
+-	O
+induced	O
+status	B-Disease
+epilepticus	I-Disease
+(	O
+SE	B-Disease
+)	O
+.	O
+
+We	O
+compared	O
+the	O
+effects	O
+of	O
+17beta	B-Chemical
+-	I-Chemical
+estradiol	I-Chemical
+in	O
+adult	O
+male	O
+and	O
+ovariectomized	O
+female	O
+rats	O
+subjected	O
+to	O
+lithium	B-Chemical
+-	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+SE	B-Disease
+.	O
+
+Rats	O
+received	O
+subcutaneous	O
+injections	O
+of	O
+17beta	B-Chemical
+-	I-Chemical
+estradiol	I-Chemical
+(	O
+2	O
+microg	O
+/	O
+rat	O
+)	O
+or	O
+oil	O
+once	O
+daily	O
+for	O
+four	O
+consecutive	O
+days	O
+.	O
+
+SE	B-Disease
+was	O
+induced	O
+20	O
+h	O
+following	O
+the	O
+second	O
+injection	O
+and	O
+terminated	O
+3	O
+h	O
+later	O
+.	O
+
+The	O
+extent	O
+of	O
+silver	B-Chemical
+-	O
+stained	O
+CA3	O
+and	O
+CA1	O
+hippocampal	O
+neurons	O
+was	O
+evaluated	O
+2	O
+days	O
+after	O
+SE	B-Disease
+.	O
+
+17beta	B-Chemical
+-	I-Chemical
+Estradiol	I-Chemical
+did	O
+not	O
+alter	O
+the	O
+onset	O
+of	O
+first	O
+clonus	O
+in	O
+ovariectomized	O
+rats	O
+but	O
+accelerated	O
+it	O
+in	O
+males	O
+.	O
+
+17beta	B-Chemical
+-	I-Chemical
+Estradiol	I-Chemical
+reduced	O
+the	O
+argyrophilic	O
+neurons	O
+in	O
+the	O
+CA1	O
+and	O
+CA3	O
+-	O
+C	O
+sectors	O
+of	O
+ovariectomized	O
+rats	O
+.	O
+
+In	O
+males	O
+,	O
+estradiol	B-Chemical
+increased	O
+the	O
+total	O
+damage	O
+score	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+the	O
+effects	O
+of	O
+estradiol	B-Chemical
+on	O
+seizure	B-Disease
+threshold	O
+and	O
+damage	O
+may	O
+be	O
+altered	O
+by	O
+sex	O
+-	O
+related	O
+differences	O
+in	O
+the	O
+hormonal	O
+environment	O
+.	O
+
+Pseudoacromegaly	B-Disease
+induced	O
+by	O
+the	O
+long	O
+-	O
+term	O
+use	O
+of	O
+minoxidil	B-Chemical
+.	O
+
+Acromegaly	B-Disease
+is	O
+an	O
+endocrine	B-Disease
+disorder	I-Disease
+caused	O
+by	O
+chronic	O
+excessive	O
+growth	O
+hormone	O
+secretion	O
+from	O
+the	O
+anterior	O
+pituitary	O
+gland	O
+.	O
+
+Significant	O
+disfiguring	O
+changes	O
+occur	O
+as	O
+a	O
+result	O
+of	O
+bone	O
+,	O
+cartilage	O
+,	O
+and	O
+soft	O
+tissue	O
+hypertrophy	B-Disease
+,	O
+including	O
+the	O
+thickening	O
+of	O
+the	O
+skin	O
+,	O
+coarsening	O
+of	O
+facial	O
+features	O
+,	O
+and	O
+cutis	B-Disease
+verticis	I-Disease
+gyrata	I-Disease
+.	O
+
+Pseudoacromegaly	B-Disease
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+is	O
+the	O
+presence	O
+of	O
+similar	O
+acromegaloid	O
+features	O
+in	O
+the	O
+absence	O
+of	O
+elevated	O
+growth	O
+hormone	O
+or	O
+insulin	O
+-	O
+like	O
+growth	O
+factor	O
+levels	O
+.	O
+
+We	O
+present	O
+a	O
+patient	O
+with	O
+pseudoacromegaly	B-Disease
+that	O
+resulted	O
+from	O
+the	O
+long	O
+-	O
+term	O
+use	O
+of	O
+minoxidil	B-Chemical
+at	O
+an	O
+unusually	O
+high	O
+dose	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+case	O
+report	O
+of	O
+pseudoacromegaly	B-Disease
+as	O
+a	O
+side	O
+effect	O
+of	O
+minoxidil	B-Chemical
+use	O
+.	O
+
+Combined	O
+androgen	O
+blockade	O
+-	O
+induced	O
+anemia	B-Disease
+in	O
+prostate	B-Disease
+cancer	I-Disease
+patients	O
+without	O
+bone	O
+involvement	O
+.	O
+
+BACKGROUND	O
+:	O
+To	O
+determine	O
+the	O
+onset	O
+and	O
+extent	O
+of	O
+combined	O
+androgen	O
+blockade	O
+(	O
+CAB	O
+)	O
+-	O
+induced	O
+anemia	B-Disease
+in	O
+prostate	B-Disease
+cancer	I-Disease
+patients	O
+without	O
+bone	O
+involvement	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Forty	O
+-	O
+two	O
+patients	O
+with	O
+biopsy	O
+-	O
+proven	O
+prostatic	B-Disease
+adenocarcinoma	I-Disease
+[	O
+26	O
+with	O
+stage	O
+C	O
+(	O
+T3N0M0	O
+)	O
+and	O
+16	O
+with	O
+stage	O
+D1	O
+(	O
+T3N1M0	O
+)	O
+]	O
+were	O
+included	O
+in	O
+this	O
+study	O
+.	O
+
+All	O
+patients	O
+received	O
+CAB	O
+[	O
+leuprolide	B-Chemical
+acetate	I-Chemical
+(	O
+LHRH	B-Chemical
+-	I-Chemical
+A	I-Chemical
+)	O
+3	O
+.	O
+75	O
+mg	O
+,	O
+intramuscularly	O
+,	O
+every	O
+28	O
+days	O
+plus	O
+250	O
+mg	O
+flutamide	B-Chemical
+,	O
+tid	O
+,	O
+per	O
+Os	O
+]	O
+and	O
+were	O
+evaluated	O
+for	O
+anemia	B-Disease
+by	O
+physical	O
+examination	O
+and	O
+laboratory	O
+tests	O
+at	O
+baseline	O
+and	O
+4	O
+subsequent	O
+intervals	O
+(	O
+1	O
+,	O
+2	O
+,	O
+3	O
+and	O
+6	O
+months	O
+post	O
+-	O
+CAB	O
+)	O
+.	O
+
+Hb	O
+,	O
+PSA	O
+and	O
+Testosterone	B-Chemical
+measurements	O
+were	O
+recorded	O
+.	O
+
+Patients	O
+with	O
+stage	O
+D2	O
+-	O
+3	O
+disease	O
+,	O
+abnormal	O
+hemoglobin	O
+level	O
+or	O
+renal	O
+and	O
+liver	O
+function	O
+tests	O
+that	O
+were	O
+higher	O
+than	O
+the	O
+upper	O
+limits	O
+were	O
+excluded	O
+from	O
+the	O
+study	O
+.	O
+
+The	O
+duration	O
+of	O
+the	O
+study	O
+was	O
+six	O
+months	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+mean	O
+hemoglobin	O
+(	O
+Hb	O
+)	O
+levels	O
+were	O
+significantly	O
+declined	O
+in	O
+all	O
+patients	O
+from	O
+baseline	O
+of	O
+14	O
+.	O
+2	O
+g	O
+/	O
+dl	O
+to	O
+14	O
+.	O
+0	O
+g	O
+/	O
+dl	O
+,	O
+13	O
+.	O
+5	O
+g	O
+/	O
+dl	O
+,	O
+13	O
+.	O
+2	O
+g	O
+/	O
+dl	O
+and	O
+12	O
+.	O
+7	O
+g	O
+/	O
+dl	O
+at	O
+1	O
+,	O
+2	O
+,	O
+3	O
+and	O
+6	O
+months	O
+post	O
+-	O
+CAB	O
+,	O
+respectively	O
+.	O
+
+Severe	O
+and	O
+clinically	O
+evident	O
+anemia	B-Disease
+of	O
+Hb	O
+<	O
+11	O
+g	O
+/	O
+dl	O
+with	O
+clinical	O
+symptoms	O
+was	O
+detected	O
+in	O
+6	O
+patients	O
+(	O
+14	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+This	O
+CAB	O
+-	O
+induced	O
+anemia	B-Disease
+was	O
+normochromic	O
+and	O
+normocytic	O
+.	O
+
+At	O
+six	O
+months	O
+post	O
+-	O
+CAB	O
+,	O
+patients	O
+with	O
+severe	O
+anemia	B-Disease
+had	O
+a	O
+Hb	O
+mean	O
+value	O
+of	O
+10	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+1	O
+g	O
+/	O
+dl	O
+(	O
+X	O
++	O
+/	O
+-	O
+SE	O
+)	O
+,	O
+whereas	O
+the	O
+other	O
+patients	O
+had	O
+mild	O
+anemia	B-Disease
+with	O
+Hb	O
+mean	O
+value	O
+of	O
+13	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+(	O
+X	O
++	O
+/	O
+-	O
+SE	O
+)	O
+.	O
+
+The	O
+development	O
+of	O
+severe	O
+anemia	B-Disease
+at	O
+6	O
+months	O
+post	O
+-	O
+CAB	O
+was	O
+predictable	O
+by	O
+the	O
+reduction	O
+of	O
+Hb	O
+baseline	O
+value	O
+of	O
+more	O
+than	O
+2	O
+.	O
+5	O
+g	O
+/	O
+dl	O
+after	O
+3	O
+months	O
+of	O
+CAB	O
+(	O
+p	O
+=	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+development	O
+of	O
+severe	O
+CAB	O
+-	O
+induced	O
+anemia	B-Disease
+in	O
+prostate	B-Disease
+cancer	I-Disease
+patients	O
+did	O
+not	O
+correlate	O
+with	O
+T	O
+baseline	O
+values	O
+(	O
+T	O
+<	O
+3	O
+ng	O
+/	O
+ml	O
+versus	O
+T	O
+>	O
+or	O
+=	O
+3	O
+ng	O
+/	O
+ml	O
+)	O
+,	O
+with	O
+age	O
+(	O
+<	O
+76	O
+yrs	O
+versus	O
+>	O
+or	O
+=	O
+76	O
+yrs	O
+)	O
+,	O
+and	O
+clinical	O
+stage	O
+(	O
+stage	O
+C	O
+versus	O
+stage	O
+D1	O
+)	O
+.	O
+
+Severe	O
+and	O
+clinically	O
+evident	O
+anemia	B-Disease
+was	O
+easily	O
+corrected	O
+by	O
+subcutaneous	O
+injections	O
+(	O
+3	O
+times	O
+/	O
+week	O
+for	O
+1	O
+month	O
+)	O
+of	O
+recombinant	O
+erythropoietin	O
+(	O
+rHuEPO	O
+-	O
+beta	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+Our	O
+data	O
+suggest	O
+that	O
+rHuEPO	O
+-	O
+beta	O
+correctable	O
+CAB	O
+-	O
+induced	O
+anemia	B-Disease
+occurs	O
+in	O
+14	O
+.	O
+3	O
+%	O
+of	O
+prostate	B-Disease
+cancer	I-Disease
+patients	O
+after	O
+6	O
+months	O
+of	O
+therapy	O
+.	O
+
+Delirium	B-Disease
+during	O
+clozapine	B-Chemical
+treatment	O
+:	O
+incidence	O
+and	O
+associated	O
+risk	O
+factors	O
+.	O
+
+BACKGROUND	O
+:	O
+Incidence	O
+and	O
+risk	O
+factors	O
+for	O
+delirium	B-Disease
+during	O
+clozapine	B-Chemical
+treatment	O
+require	O
+further	O
+clarification	O
+.	O
+
+METHODS	O
+:	O
+We	O
+used	O
+computerized	O
+pharmacy	O
+records	O
+to	O
+identify	O
+all	O
+adult	O
+psychiatric	B-Disease
+inpatients	O
+treated	O
+with	O
+clozapine	B-Chemical
+(	O
+1995	O
+-	O
+96	O
+)	O
+,	O
+reviewed	O
+their	O
+medical	O
+records	O
+to	O
+score	O
+incidence	O
+and	O
+severity	O
+of	O
+delirium	B-Disease
+,	O
+and	O
+tested	O
+associations	O
+with	O
+potential	O
+risk	O
+factors	O
+.	O
+
+RESULTS	O
+:	O
+Subjects	O
+(	O
+n	O
+=	O
+139	O
+)	O
+were	O
+72	O
+women	O
+and	O
+67	O
+men	O
+,	O
+aged	O
+40	O
+.	O
+8	O
++	O
+/	O
+-	O
+12	O
+.	O
+1	O
+years	O
+,	O
+hospitalized	O
+for	O
+24	O
+.	O
+9	O
++	O
+/	O
+-	O
+23	O
+.	O
+3	O
+days	O
+,	O
+and	O
+given	O
+clozapine	B-Chemical
+,	O
+gradually	O
+increased	O
+to	O
+an	O
+average	O
+daily	O
+dose	O
+of	O
+282	O
++	O
+/	O
+-	O
+203	O
+mg	O
+(	O
+3	O
+.	O
+45	O
++	O
+/	O
+-	O
+2	O
+.	O
+45	O
+mg	O
+/	O
+kg	O
+)	O
+for	O
+18	O
+.	O
+9	O
++	O
+/	O
+-	O
+16	O
+.	O
+4	O
+days	O
+.	O
+
+Delirium	B-Disease
+was	O
+diagnosed	O
+in	O
+14	O
+(	O
+10	O
+.	O
+1	O
+%	O
+incidence	O
+,	O
+or	O
+1	O
+.	O
+48	O
+cases	O
+/	O
+person	O
+-	O
+years	O
+of	O
+exposure	O
+)	O
+;	O
+71	O
+.	O
+4	O
+%	O
+of	O
+cases	O
+were	O
+moderate	O
+or	O
+severe	O
+.	O
+
+Associated	O
+factors	O
+were	O
+co	O
+-	O
+treatment	O
+with	O
+other	O
+centrally	O
+antimuscarinic	O
+agents	O
+,	O
+poor	O
+clinical	O
+outcome	O
+,	O
+older	O
+age	O
+,	O
+and	O
+longer	O
+hospitalization	O
+(	O
+by	O
+17	O
+.	O
+5	O
+days	O
+,	O
+increasing	O
+cost	O
+)	O
+;	O
+sex	O
+,	O
+diagnosis	O
+or	O
+medical	O
+co	O
+-	O
+morbidity	O
+,	O
+and	O
+daily	O
+clozapine	B-Chemical
+dose	O
+,	O
+which	O
+fell	O
+with	O
+age	O
+,	O
+were	O
+unrelated	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Delirium	B-Disease
+was	O
+found	O
+in	O
+10	O
+%	O
+of	O
+clozapine	B-Chemical
+-	O
+treated	O
+inpatients	O
+,	O
+particularly	O
+in	O
+older	O
+patients	O
+exposed	O
+to	O
+other	O
+central	O
+anticholinergics	O
+.	O
+
+Delirium	B-Disease
+was	O
+inconsistently	O
+recognized	O
+clinically	O
+in	O
+milder	O
+cases	O
+and	O
+was	O
+associated	O
+with	O
+increased	O
+length	O
+-	O
+of	O
+-	O
+stay	O
+and	O
+higher	O
+costs	O
+,	O
+and	O
+inferior	O
+clinical	O
+outcome	O
+.	O
+
+Neuroprotective	O
+action	O
+of	O
+MPEP	B-Chemical
+,	O
+a	O
+selective	O
+mGluR5	O
+antagonist	O
+,	O
+in	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+dopaminergic	O
+neurotoxicity	B-Disease
+is	O
+associated	O
+with	O
+a	O
+decrease	O
+in	O
+dopamine	B-Chemical
+outflow	O
+and	O
+inhibition	O
+of	O
+hyperthermia	B-Disease
+in	O
+rats	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+examine	O
+the	O
+role	O
+of	O
+metabotropic	O
+glutamate	B-Chemical
+receptor	O
+5	O
+(	O
+mGluR5	O
+)	O
+in	O
+the	O
+toxic	O
+action	O
+of	O
+methamphetamine	B-Chemical
+on	O
+dopaminergic	O
+neurones	O
+in	O
+rats	O
+.	O
+
+Methamphetamine	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+sc	O
+)	O
+,	O
+administered	O
+five	O
+times	O
+,	O
+reduced	O
+the	O
+levels	O
+of	O
+dopamine	B-Chemical
+and	O
+its	O
+metabolites	O
+in	O
+striatal	O
+tissue	O
+when	O
+measured	O
+72	O
+h	O
+after	O
+the	O
+last	O
+injection	O
+.	O
+
+A	O
+selective	O
+antagonist	O
+of	O
+mGluR5	O
+,	O
+2	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+6	I-Chemical
+-	I-Chemical
+(	I-Chemical
+phenylethynyl	I-Chemical
+)	I-Chemical
+pyridine	I-Chemical
+(	O
+MPEP	B-Chemical
+;	O
+5	O
+mg	O
+/	O
+kg	O
+ip	O
+)	O
+,	O
+when	O
+administered	O
+five	O
+times	O
+immediately	O
+before	O
+each	O
+methamphetamine	B-Chemical
+injection	O
+reversed	O
+the	O
+above	O
+-	O
+mentioned	O
+methamphetamine	B-Chemical
+effects	O
+.	O
+
+A	O
+single	O
+MPEP	B-Chemical
+(	O
+5	O
+mg	O
+/	O
+kg	O
+ip	O
+)	O
+injection	O
+reduced	O
+the	O
+basal	O
+extracellular	O
+dopamine	B-Chemical
+level	O
+in	O
+the	O
+striatum	O
+,	O
+as	O
+well	O
+as	O
+dopamine	B-Chemical
+release	O
+stimulated	O
+either	O
+by	O
+methamphetamine	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+sc	O
+)	O
+or	O
+by	O
+intrastriatally	O
+administered	O
+veratridine	B-Chemical
+(	O
+100	O
+microM	O
+)	O
+.	O
+
+Moreover	O
+,	O
+it	O
+transiently	O
+diminished	O
+the	O
+methamphetamine	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+sc	O
+)	O
+-	O
+induced	O
+hyperthermia	B-Disease
+and	O
+reduced	O
+basal	O
+body	O
+temperature	O
+.	O
+
+MPEP	B-Chemical
+administered	O
+into	O
+the	O
+striatum	O
+at	O
+high	O
+concentrations	O
+(	O
+500	O
+microM	O
+)	O
+increased	O
+extracellular	O
+dopamine	B-Chemical
+levels	O
+,	O
+while	O
+lower	O
+concentrations	O
+(	O
+50	O
+-	O
+100	O
+microM	O
+)	O
+were	O
+devoid	O
+of	O
+any	O
+effect	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+study	O
+suggest	O
+that	O
+the	O
+blockade	O
+of	O
+mGluR5	O
+by	O
+MPEP	B-Chemical
+may	O
+protect	O
+dopaminergic	O
+neurones	O
+against	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+toxicity	B-Disease
+.	O
+
+Neuroprotection	O
+rendered	O
+by	O
+MPEP	B-Chemical
+may	O
+be	O
+associated	O
+with	O
+the	O
+reduction	O
+of	O
+the	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+dopamine	B-Chemical
+efflux	O
+in	O
+the	O
+striatum	O
+due	O
+to	O
+the	O
+blockade	O
+of	O
+extrastriatal	O
+mGluR5	O
+,	O
+and	O
+with	O
+a	O
+decrease	O
+in	O
+hyperthermia	B-Disease
+.	O
+
+Protective	O
+efficacy	O
+of	O
+neuroactive	O
+steroids	B-Chemical
+against	O
+cocaine	B-Chemical
+kindled	O
+-	O
+seizures	B-Disease
+in	O
+mice	O
+.	O
+
+Neuroactive	O
+steroids	B-Chemical
+demonstrate	O
+pharmacological	O
+actions	O
+that	O
+have	O
+relevance	O
+for	O
+a	O
+host	O
+of	O
+neurological	B-Disease
+and	I-Disease
+psychiatric	I-Disease
+disorders	I-Disease
+.	O
+
+They	O
+offer	O
+protection	O
+against	O
+seizures	B-Disease
+in	O
+a	O
+range	O
+of	O
+models	O
+and	O
+seem	O
+to	O
+inhibit	O
+certain	O
+stages	O
+of	O
+drug	B-Disease
+dependence	I-Disease
+in	O
+preclinical	O
+assessments	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+evaluate	O
+two	O
+endogenous	O
+and	O
+one	O
+synthetic	O
+neuroactive	O
+steroid	B-Chemical
+that	O
+positively	O
+modulate	O
+the	O
+gamma	B-Chemical
+-	I-Chemical
+aminobutyric	I-Chemical
+acid	I-Chemical
+(	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+)	O
+receptor	O
+against	O
+the	O
+increase	O
+in	O
+sensitivity	O
+to	O
+the	O
+convulsant	O
+effects	O
+of	O
+cocaine	B-Chemical
+engendered	O
+by	O
+repeated	O
+cocaine	B-Chemical
+administration	O
+(	O
+seizure	B-Disease
+kindling	O
+)	O
+.	O
+
+Allopregnanolone	B-Chemical
+(	O
+3alpha	B-Chemical
+-	I-Chemical
+hydroxy	I-Chemical
+-	I-Chemical
+5alpha	I-Chemical
+-	I-Chemical
+pregnan	I-Chemical
+-	I-Chemical
+20	I-Chemical
+-	I-Chemical
+one	I-Chemical
+)	O
+,	O
+pregnanolone	B-Chemical
+(	O
+3alpha	B-Chemical
+-	I-Chemical
+hydroxy	I-Chemical
+-	I-Chemical
+5beta	I-Chemical
+-	I-Chemical
+pregnan	I-Chemical
+-	I-Chemical
+20	I-Chemical
+-	I-Chemical
+one	I-Chemical
+)	O
+and	O
+ganaxolone	B-Chemical
+(	O
+a	O
+synthetic	O
+derivative	O
+of	O
+allopregnanolone	B-Chemical
+3alpha	B-Chemical
+-	I-Chemical
+hydroxy	I-Chemical
+-	I-Chemical
+3beta	I-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+5alpha	I-Chemical
+-	I-Chemical
+pregnan	I-Chemical
+-	I-Chemical
+20	I-Chemical
+-	I-Chemical
+one	I-Chemical
+)	O
+were	O
+tested	O
+for	O
+their	O
+ability	O
+to	O
+suppress	O
+the	O
+expression	O
+(	O
+anticonvulsant	O
+effect	O
+)	O
+and	O
+development	O
+(	O
+antiepileptogenic	O
+effect	O
+)	O
+of	O
+cocaine	B-Chemical
+-	O
+kindled	O
+seizures	B-Disease
+in	O
+male	O
+,	O
+Swiss	O
+-	O
+Webster	O
+mice	O
+.	O
+
+Kindled	O
+seizures	B-Disease
+were	O
+induced	O
+by	O
+daily	O
+administration	O
+of	O
+60	O
+mg	O
+/	O
+kg	O
+cocaine	B-Chemical
+for	O
+5	O
+days	O
+.	O
+
+All	O
+of	O
+these	O
+positive	O
+GABA	B-Chemical
+(	O
+A	O
+)	O
+modulators	O
+suppressed	O
+the	O
+expression	O
+of	O
+kindled	O
+seizures	B-Disease
+,	O
+whereas	O
+only	O
+allopregnanolone	B-Chemical
+and	O
+ganaxolone	B-Chemical
+inhibited	O
+the	O
+development	O
+of	O
+kindling	O
+.	O
+
+Allopregnanolone	B-Chemical
+and	O
+pregnanolone	B-Chemical
+,	O
+but	O
+not	O
+ganaxolone	B-Chemical
+,	O
+also	O
+reduced	O
+cumulative	O
+lethality	O
+associated	O
+with	O
+kindling	O
+.	O
+
+These	O
+findings	O
+demonstrate	O
+that	O
+some	O
+neuroactive	O
+steroids	B-Chemical
+attenuate	O
+convulsant	O
+and	O
+sensitizing	O
+properties	O
+of	O
+cocaine	B-Chemical
+and	O
+add	O
+to	O
+a	O
+growing	O
+literature	O
+on	O
+their	O
+potential	O
+use	O
+in	O
+the	O
+modulation	O
+of	O
+effects	O
+of	O
+drugs	O
+of	O
+abuse	O
+.	O
+
+Effect	O
+of	O
+humoral	O
+modulators	O
+of	O
+morphine	B-Chemical
+-	O
+induced	O
+increase	B-Disease
+in	I-Disease
+locomotor	I-Disease
+activity	I-Disease
+of	O
+mice	O
+.	O
+
+The	O
+effect	O
+of	O
+humoral	O
+modulators	O
+on	O
+the	O
+morphine	B-Chemical
+-	O
+induced	O
+increase	B-Disease
+in	I-Disease
+locomotor	I-Disease
+activity	I-Disease
+of	O
+mice	O
+was	O
+studied	O
+.	O
+
+The	O
+subcutaneous	O
+administration	O
+of	O
+10	O
+mg	O
+/	O
+kg	O
+of	O
+morphine	B-Chemical
+-	O
+HC1	O
+produced	O
+a	O
+marked	O
+increase	B-Disease
+in	I-Disease
+locomotor	I-Disease
+activity	I-Disease
+in	O
+mice	O
+.	O
+
+The	O
+morphine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+was	O
+potentiated	O
+by	O
+scopolamine	B-Chemical
+and	O
+attenuated	O
+by	O
+physostigmine	B-Chemical
+.	O
+
+In	O
+contrast	O
+,	O
+both	O
+methscopolamine	B-Chemical
+and	O
+neostigmine	B-Chemical
+,	O
+which	O
+do	O
+not	O
+penetrate	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+,	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+hyperactivity	B-Disease
+produced	O
+by	O
+morphine	B-Chemical
+.	O
+
+Pretreatment	O
+of	O
+mice	O
+with	O
+alpha	B-Chemical
+-	I-Chemical
+methyltyrosine	I-Chemical
+(	O
+20	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+,	O
+one	O
+hour	O
+)	O
+,	O
+an	O
+inhibitor	O
+of	O
+tyrosine	B-Chemical
+hydroxylase	O
+,	O
+significantly	O
+decreased	O
+the	O
+activity	O
+-	O
+increasing	O
+effects	O
+of	O
+morphine	B-Chemical
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+pretreatment	O
+with	O
+p	B-Chemical
+-	I-Chemical
+chlorophenylalamine	I-Chemical
+(	O
+3	O
+X	O
+320	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+,	O
+24	O
+hr	O
+)	O
+,	O
+a	O
+serotonin	B-Chemical
+depletor	O
+,	O
+caused	O
+no	O
+significant	O
+change	O
+in	O
+the	O
+hyperactivity	B-Disease
+.	O
+
+The	O
+study	O
+suggests	O
+that	O
+the	O
+activity	O
+-	O
+increasing	O
+effects	O
+of	O
+morphine	B-Chemical
+are	O
+mediated	O
+by	O
+the	O
+release	O
+of	O
+catecholamines	B-Chemical
+from	O
+adrenergic	O
+neurons	O
+in	O
+the	O
+brain	O
+.	O
+
+And	O
+the	O
+results	O
+are	O
+consistent	O
+with	O
+the	O
+hypothesis	O
+that	O
+morphine	B-Chemical
+acts	O
+by	O
+retarding	O
+the	O
+release	O
+of	O
+acetylcholine	B-Chemical
+at	O
+some	O
+central	O
+cholinergic	O
+synapses	O
+.	O
+
+It	O
+is	O
+also	O
+suggested	O
+from	O
+collected	O
+evidence	O
+that	O
+the	O
+activity	O
+-	O
+increasing	O
+effects	O
+of	O
+morphine	B-Chemical
+in	O
+mice	O
+are	O
+mediated	O
+by	O
+mechanisms	O
+different	O
+from	O
+those	O
+which	O
+mediate	O
+the	O
+activity	O
+-	O
+increasing	O
+effects	O
+of	O
+morphine	B-Chemical
+in	O
+rats	O
+.	O
+
+Effects	O
+of	O
+uninephrectomy	O
+and	O
+high	O
+protein	O
+feeding	O
+on	O
+lithium	B-Chemical
+-	O
+induced	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+in	O
+rats	O
+.	O
+
+Rats	O
+with	O
+lithium	B-Chemical
+-	O
+induced	O
+nephropathy	B-Disease
+were	O
+subjected	O
+to	O
+high	O
+protein	O
+(	O
+HP	O
+)	O
+feeding	O
+,	O
+uninephrectomy	O
+(	O
+NX	O
+)	O
+or	O
+a	O
+combination	O
+of	O
+these	O
+,	O
+in	O
+an	O
+attempt	O
+to	O
+induce	O
+glomerular	O
+hyperfiltration	O
+and	O
+further	O
+progression	O
+of	O
+renal	B-Disease
+failure	I-Disease
+.	O
+
+Newborn	O
+female	O
+Wistar	O
+rats	O
+were	O
+fed	O
+a	O
+lithium	B-Chemical
+-	O
+containing	O
+diet	O
+(	O
+50	O
+mmol	O
+/	O
+kg	O
+)	O
+for	O
+8	O
+weeks	O
+and	O
+then	O
+randomized	O
+to	O
+normal	O
+diet	O
+,	O
+HP	O
+diet	O
+(	O
+40	O
+vs	O
+.	O
+19	O
+%	O
+)	O
+,	O
+NX	O
+or	O
+HP	O
++	O
+NX	O
+for	O
+another	O
+8	O
+weeks	O
+.	O
+
+Corresponding	O
+non	O
+-	O
+lithium	B-Chemical
+pretreated	O
+groups	O
+were	O
+generated	O
+.	O
+
+When	O
+comparing	O
+all	O
+lithium	B-Chemical
+treated	O
+versus	O
+non	O
+-	O
+lithium	B-Chemical
+-	O
+treated	O
+groups	O
+,	O
+lithium	B-Chemical
+caused	O
+a	O
+reduction	O
+in	O
+glomerular	O
+filtration	O
+rate	O
+(	O
+GFR	O
+)	O
+without	O
+significant	O
+changes	O
+in	O
+effective	O
+renal	O
+plasma	O
+flow	O
+(	O
+as	O
+determined	O
+by	O
+a	O
+marker	O
+secreted	O
+into	O
+the	O
+proximal	O
+tubules	O
+)	O
+or	O
+lithium	B-Chemical
+clearance	O
+.	O
+
+Consequently	O
+,	O
+lithium	B-Chemical
+pretreatment	O
+caused	O
+a	O
+fall	O
+in	O
+filtration	O
+fraction	O
+and	O
+an	O
+increase	O
+in	O
+fractional	O
+Li	B-Chemical
+excretion	O
+.	O
+
+Lithium	B-Chemical
+also	O
+caused	O
+proteinuria	B-Disease
+and	O
+systolic	O
+hypertension	B-Disease
+in	O
+absence	O
+of	O
+glomerulosclerosis	B-Disease
+.	O
+
+HP	O
+failed	O
+to	O
+accentuante	O
+progression	O
+of	O
+renal	B-Disease
+failure	I-Disease
+and	O
+in	O
+fact	O
+tended	O
+to	O
+increase	O
+GFR	O
+and	O
+decrease	O
+plasma	O
+creatinine	B-Chemical
+levels	O
+in	O
+lithium	B-Chemical
+pretreated	O
+rats	O
+.	O
+
+NX	O
+caused	O
+an	O
+additive	O
+deterioration	O
+in	O
+GFR	O
+which	O
+,	O
+however	O
+,	O
+was	O
+ameliorated	O
+by	O
+HP	O
+.	O
+
+NX	O
++	O
+HP	O
+caused	O
+a	O
+further	O
+rise	O
+in	O
+blood	O
+pressure	O
+in	O
+Li	B-Chemical
+-	O
+pretreated	O
+rats	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+Li	B-Chemical
+-	O
+induced	O
+nephropathy	B-Disease
+,	O
+even	O
+when	O
+the	O
+GFR	O
+is	O
+only	O
+modestly	O
+reduced	O
+,	O
+is	O
+associated	O
+with	O
+proteinuria	B-Disease
+and	O
+arterial	O
+systolic	O
+hypertension	B-Disease
+.	O
+
+In	O
+this	O
+model	O
+of	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+the	O
+decline	O
+in	O
+GFR	O
+is	O
+not	O
+accompanied	O
+by	O
+a	O
+corresponding	O
+fall	O
+in	O
+effective	O
+renal	O
+plasma	O
+flow	O
+,	O
+which	O
+may	O
+be	O
+the	O
+functional	O
+expression	O
+of	O
+the	O
+formation	O
+of	O
+nonfiltrating	O
+atubular	O
+glomeruli	O
+.	O
+
+The	O
+fractional	O
+reabsorption	O
+of	O
+tubular	O
+fluid	O
+by	O
+the	O
+proximal	O
+tubules	O
+is	O
+reduced	O
+,	O
+leaving	O
+the	O
+distal	O
+delivery	O
+unchanged	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Treatment	O
+of	O
+Crohn	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+with	O
+fusidic	B-Chemical
+acid	I-Chemical
+:	O
+an	O
+antibiotic	O
+with	O
+immunosuppressive	O
+properties	O
+similar	O
+to	O
+cyclosporin	B-Chemical
+.	O
+
+Fusidic	O
+acid	O
+is	O
+an	O
+antibiotic	O
+with	O
+T	O
+-	O
+cell	O
+specific	O
+immunosuppressive	O
+effects	O
+similar	O
+to	O
+those	O
+of	O
+cyclosporin	B-Chemical
+.	O
+
+Because	O
+of	O
+the	O
+need	O
+for	O
+the	O
+development	O
+of	O
+new	O
+treatments	O
+for	O
+Crohn	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+,	O
+a	O
+pilot	O
+study	O
+was	O
+undertaken	O
+to	O
+estimate	O
+the	O
+pharmacodynamics	O
+and	O
+tolerability	O
+of	O
+fusidic	B-Chemical
+acid	I-Chemical
+treatment	O
+in	O
+chronic	O
+active	O
+,	O
+therapy	O
+-	O
+resistant	O
+patients	O
+.	O
+
+Eight	O
+Crohn	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+patients	O
+were	O
+included	O
+.	O
+
+Fusidic	B-Chemical
+acid	I-Chemical
+was	O
+administered	O
+orally	O
+in	O
+a	O
+dose	O
+of	O
+500	O
+mg	O
+t	O
+.	O
+d	O
+.	O
+s	O
+.	O
+and	O
+the	O
+treatment	O
+was	O
+planned	O
+to	O
+last	O
+8	O
+weeks	O
+.	O
+
+The	O
+disease	O
+activity	O
+was	O
+primarily	O
+measured	O
+by	O
+a	O
+modified	O
+individual	O
+grading	O
+score	O
+.	O
+
+Five	O
+of	O
+8	O
+patients	O
+(	O
+63	O
+%	O
+)	O
+improved	O
+during	O
+fusidic	B-Chemical
+acid	I-Chemical
+treatment	O
+:	O
+3	O
+at	O
+two	O
+weeks	O
+and	O
+2	O
+after	O
+four	O
+weeks	O
+.	O
+
+There	O
+were	O
+no	O
+serious	O
+clinical	O
+side	O
+effects	O
+,	O
+but	O
+dose	O
+reduction	O
+was	O
+required	O
+in	O
+two	O
+patients	O
+because	O
+of	O
+nausea	B-Disease
+.	O
+
+Biochemically	O
+,	O
+an	O
+increase	O
+in	O
+alkaline	O
+phosphatases	O
+was	O
+noted	O
+in	O
+5	O
+of	O
+8	O
+cases	O
+(	O
+63	O
+%	O
+)	O
+,	O
+and	O
+the	O
+greatest	O
+increases	O
+were	O
+seen	O
+in	O
+those	O
+who	O
+had	O
+elevated	O
+levels	O
+prior	O
+to	O
+treatment	O
+.	O
+
+All	O
+reversed	O
+to	O
+pre	O
+-	O
+treatment	O
+levels	O
+after	O
+cessation	O
+of	O
+treatment	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+pilot	O
+study	O
+suggest	O
+that	O
+fusidic	B-Chemical
+acid	I-Chemical
+may	O
+be	O
+of	O
+benefit	O
+in	O
+selected	O
+chronic	O
+active	O
+Crohn	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+patients	O
+in	O
+whom	O
+conventional	O
+treatment	O
+is	O
+ineffective	O
+.	O
+
+Because	O
+there	O
+seems	O
+to	O
+exist	O
+a	O
+scientific	O
+rationale	O
+for	O
+the	O
+use	O
+of	O
+fusidic	B-Chemical
+acid	I-Chemical
+at	O
+the	O
+cytokine	O
+level	O
+in	O
+inflammatory	B-Disease
+bowel	I-Disease
+disease	I-Disease
+,	O
+we	O
+suggest	O
+that	O
+the	O
+role	O
+of	O
+this	O
+treatment	O
+should	O
+be	O
+further	O
+investigated	O
+.	O
+
+Changes	O
+in	O
+depressive	B-Disease
+status	O
+associated	O
+with	O
+topical	O
+beta	O
+-	O
+blockers	O
+.	O
+
+Depression	B-Disease
+and	O
+sexual	B-Disease
+dysfunction	I-Disease
+have	O
+been	O
+related	O
+to	O
+side	O
+effects	O
+of	O
+topical	O
+beta	O
+-	O
+blockers	O
+.	O
+
+We	O
+performed	O
+a	O
+preliminary	O
+study	O
+in	O
+order	O
+to	O
+determine	O
+any	O
+difference	O
+between	O
+a	O
+non	O
+selective	O
+beta	O
+-	O
+blocker	O
+(	O
+timolol	B-Chemical
+)	O
+and	O
+a	O
+selective	O
+beta	O
+-	O
+blocker	O
+(	O
+betaxolol	B-Chemical
+)	O
+regarding	O
+CNS	O
+side	O
+effects	O
+.	O
+
+Eight	O
+glaucomatous	B-Disease
+patients	O
+chronically	O
+treated	O
+with	O
+timolol	B-Chemical
+0	O
+.	O
+5	O
+%	O
+/	O
+12h	O
+,	O
+suffering	O
+from	O
+depression	B-Disease
+diagnosed	O
+through	O
+DMS	O
+-	O
+III	O
+-	O
+R	O
+criteria	O
+,	O
+were	O
+included	O
+in	O
+the	O
+study	O
+.	O
+
+During	O
+the	O
+six	O
+-	O
+month	O
+follow	O
+up	O
+,	O
+depression	B-Disease
+was	O
+quantified	O
+through	O
+the	O
+Beck	O
+and	O
+Zung	O
+-	O
+Conde	O
+scales	O
+every	O
+two	O
+months	O
+.	O
+
+In	O
+a	O
+double	O
+blind	O
+cross	O
+-	O
+over	O
+study	O
+with	O
+control	O
+group	O
+,	O
+the	O
+patients	O
+under	O
+timolol	B-Chemical
+treatment	O
+presented	O
+higher	O
+depression	B-Disease
+values	O
+measured	O
+through	O
+the	O
+Beck	O
+and	O
+the	O
+Zung	O
+-	O
+Conde	O
+scales	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+vs	O
+control	O
+)	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+betaxolol	B-Chemical
+could	O
+be	O
+less	O
+of	O
+a	O
+depression	B-Disease
+-	O
+inducer	O
+than	O
+timolol	B-Chemical
+in	O
+predisposed	O
+patients	O
+.	O
+
+Protection	O
+against	O
+amphetamine	B-Chemical
+-	O
+induced	O
+neurotoxicity	B-Disease
+toward	O
+striatal	O
+dopamine	B-Chemical
+neurons	O
+in	O
+rodents	O
+by	O
+LY274614	B-Chemical
+,	O
+an	O
+excitatory	O
+amino	B-Chemical
+acid	I-Chemical
+antagonist	O
+.	O
+
+LY274614	B-Chemical
+,	O
+3SR	B-Chemical
+,	I-Chemical
+4aRS	I-Chemical
+,	I-Chemical
+6SR	I-Chemical
+,	I-Chemical
+8aRS	I-Chemical
+-	I-Chemical
+6	I-Chemical
+-	I-Chemical
+[	I-Chemical
+phosphonomethyl	I-Chemical
+]	I-Chemical
+decahydr	I-Chemical
+oisoquinoline	I-Chemical
+-	I-Chemical
+3	I-Chemical
+-	I-Chemical
+carboxylic	I-Chemical
+acid	I-Chemical
+,	O
+has	O
+been	O
+described	O
+as	O
+a	O
+potent	O
+antagonist	O
+of	O
+the	O
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+D	I-Chemical
+-	I-Chemical
+aspartate	I-Chemical
+(	O
+NMDA	B-Chemical
+)	O
+subtype	O
+of	O
+glutamate	B-Chemical
+receptor	O
+.	O
+
+Here	O
+its	O
+ability	O
+to	O
+antagonize	O
+the	O
+prolonged	O
+depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+by	O
+amphetamine	B-Chemical
+in	O
+iprindole	B-Chemical
+-	O
+treated	O
+rats	O
+is	O
+reported	O
+.	O
+
+A	O
+single	O
+18	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+(	O
+i	O
+.	O
+p	O
+.	O
+)	O
+dose	O
+of	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+amphetamine	B-Chemical
+hemisulfate	O
+,	O
+given	O
+to	O
+rats	O
+pretreated	O
+with	O
+iprindole	B-Chemical
+,	O
+resulted	O
+in	O
+persistent	O
+depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+1	O
+week	O
+later	O
+.	O
+
+This	O
+prolonged	O
+depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+was	O
+antagonized	O
+by	O
+dizocilpine	B-Chemical
+(	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+,	O
+a	O
+non	O
+-	O
+competitive	O
+antagonist	O
+of	O
+NMDA	B-Chemical
+receptors	O
+)	O
+or	O
+by	O
+LY274614	B-Chemical
+(	O
+a	O
+competitive	O
+antagonist	O
+of	O
+NMDA	B-Chemical
+receptors	O
+)	O
+.	O
+
+The	O
+protective	O
+effect	O
+of	O
+LY274614	B-Chemical
+was	O
+dose	O
+-	O
+dependent	O
+,	O
+being	O
+maximum	O
+at	O
+10	O
+-	O
+40	O
+mgkg	O
+(	O
+i	O
+.	O
+p	O
+.	O
+)	O
+.	O
+
+A	O
+10	O
+mg	O
+/	O
+kg	O
+dose	O
+of	O
+LY274614	B-Chemical
+was	O
+effective	O
+in	O
+antagonizing	O
+the	O
+depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+,	O
+when	O
+given	O
+as	O
+long	O
+as	O
+8	O
+hr	O
+prior	O
+to	O
+amphetamine	B-Chemical
+but	O
+not	O
+when	O
+given	O
+24	O
+hr	O
+prior	O
+to	O
+amphetamine	B-Chemical
+.	O
+
+Depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+was	O
+also	O
+antagonized	O
+when	O
+LY274614	B-Chemical
+was	O
+given	O
+after	O
+the	O
+injection	O
+of	O
+amphetamine	B-Chemical
+;	O
+LY274614	B-Chemical
+protected	O
+when	O
+given	O
+up	O
+to	O
+4	O
+hr	O
+after	O
+but	O
+not	O
+when	O
+given	O
+8	O
+or	O
+24	O
+hr	O
+after	O
+amphetamine	B-Chemical
+.	O
+
+The	O
+prolonged	O
+depletion	O
+of	O
+dopamine	B-Chemical
+in	O
+the	O
+striatum	O
+in	O
+mice	O
+,	O
+given	O
+multiple	O
+injections	O
+of	O
+methamphetamine	B-Chemical
+,	O
+was	O
+also	O
+antagonized	O
+dose	O
+-	O
+dependently	O
+and	O
+completely	O
+by	O
+LY274614	B-Chemical
+.	O
+
+The	O
+data	O
+strengthen	O
+the	O
+evidence	O
+that	O
+the	O
+neurotoxic	B-Disease
+effect	O
+of	O
+amphetamine	B-Chemical
+and	O
+related	O
+compounds	O
+toward	O
+nigrostriatal	O
+dopamine	B-Chemical
+neurons	O
+involves	O
+NMDA	B-Chemical
+receptors	O
+and	O
+that	O
+LY274614	B-Chemical
+is	O
+an	O
+NMDA	B-Chemical
+receptor	O
+antagonist	O
+with	O
+long	O
+-	O
+lasting	O
+in	O
+vivo	O
+effects	O
+in	O
+rats	O
+.	O
+
+Ketoconazole	B-Chemical
+-	O
+induced	O
+neurologic	B-Disease
+sequelae	I-Disease
+.	O
+
+A	O
+77	O
+-	O
+y	O
+-	O
+old	O
+patient	O
+developed	O
+weakness	B-Disease
+of	I-Disease
+extremities	I-Disease
+,	O
+legs	B-Disease
+paralysis	I-Disease
+,	O
+dysarthria	B-Disease
+and	O
+tremor	B-Disease
+1	O
+h	O
+after	O
+ingestion	O
+of	O
+200	O
+mg	O
+ketoconazole	B-Chemical
+for	O
+the	O
+first	O
+time	O
+in	O
+his	O
+life	O
+.	O
+
+All	O
+complaints	O
+faded	O
+away	O
+within	O
+24	O
+h	O
+.	O
+
+Few	O
+days	O
+later	O
+,	O
+the	O
+patient	O
+used	O
+another	O
+200	O
+mg	O
+ketoconazole	B-Chemical
+tablet	O
+,	O
+and	O
+within	O
+an	O
+hour	O
+experienced	O
+a	O
+similar	O
+clinical	O
+picture	O
+,	O
+which	O
+resolved	O
+again	O
+spontaneously	O
+within	O
+hours	O
+.	O
+
+Laboratory	O
+evaluations	O
+,	O
+including	O
+head	O
+CT	O
+scan	O
+,	O
+were	O
+normal	O
+.	O
+
+This	O
+case	O
+illustrates	O
+the	O
+need	O
+for	O
+close	O
+vigilance	O
+in	O
+adverse	B-Disease
+drug	I-Disease
+reactions	I-Disease
+,	O
+particularly	O
+in	O
+the	O
+elderly	O
+.	O
+
+Development	O
+of	O
+levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+in	O
+parkinsonian	B-Disease
+monkeys	O
+may	O
+depend	O
+upon	O
+rate	O
+of	O
+symptom	O
+onset	O
+and	O
+/	O
+or	O
+duration	O
+of	O
+symptoms	O
+.	O
+
+Levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+(	O
+LIDs	B-Disease
+)	O
+present	O
+a	O
+major	O
+problem	O
+for	O
+the	O
+long	O
+-	O
+term	O
+management	O
+of	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+patients	O
+.	O
+
+Due	O
+to	O
+the	O
+interdependence	O
+of	O
+risk	O
+factors	O
+in	O
+clinical	O
+populations	O
+,	O
+it	O
+is	O
+difficult	O
+to	O
+independently	O
+examine	O
+factors	O
+that	O
+may	O
+influence	O
+the	O
+development	O
+of	O
+LIDs	B-Disease
+.	O
+
+Using	O
+macaque	O
+monkeys	O
+with	O
+different	O
+types	O
+of	O
+MPTP	B-Chemical
+-	O
+induced	O
+parkinsonism	B-Disease
+,	O
+the	O
+current	O
+study	O
+evaluated	O
+the	O
+degree	O
+to	O
+which	O
+rate	O
+of	O
+symptom	O
+progression	O
+,	O
+symptom	O
+severity	O
+,	O
+and	O
+response	O
+to	O
+and	O
+duration	O
+of	O
+levodopa	B-Chemical
+therapy	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+development	O
+of	O
+LIDs	B-Disease
+.	O
+
+Monkeys	O
+with	O
+acute	O
+(	O
+short	O
+-	O
+term	O
+)	O
+MPTP	B-Chemical
+exposure	O
+,	O
+rapid	O
+symptom	O
+onset	O
+and	O
+short	O
+symptom	O
+duration	O
+prior	O
+to	O
+initiation	O
+of	O
+levodopa	B-Chemical
+therapy	O
+developed	O
+dyskinesia	B-Disease
+between	O
+11	O
+and	O
+24	O
+days	O
+of	O
+daily	O
+levodopa	B-Chemical
+administration	O
+.	O
+
+In	O
+contrast	O
+,	O
+monkeys	O
+with	O
+long	O
+-	O
+term	O
+MPTP	B-Chemical
+exposure	O
+,	O
+slow	O
+symptom	O
+progression	O
+and	O
+/	O
+or	O
+long	O
+symptom	O
+duration	O
+prior	O
+to	O
+initiation	O
+of	O
+levodopa	B-Chemical
+therapy	O
+were	O
+more	O
+resistant	O
+to	O
+developing	O
+LIDs	B-Disease
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+dyskinesia	B-Disease
+developed	O
+no	O
+sooner	O
+than	O
+146	O
+days	O
+of	O
+chronic	O
+levodopa	B-Chemical
+administration	O
+)	O
+.	O
+
+All	O
+animals	O
+were	O
+similarly	O
+symptomatic	O
+at	O
+the	O
+start	O
+of	O
+levodopa	B-Chemical
+treatment	O
+and	O
+had	O
+similar	O
+therapeutic	O
+responses	O
+to	O
+the	O
+drug	O
+.	O
+
+These	O
+data	O
+suggest	O
+distinct	O
+differences	O
+in	O
+the	O
+propensity	O
+to	O
+develop	O
+LIDs	B-Disease
+in	O
+monkeys	O
+with	O
+different	O
+rates	O
+of	O
+symptom	O
+progression	O
+or	O
+symptom	O
+durations	O
+prior	O
+to	O
+levodopa	B-Chemical
+and	O
+demonstrate	O
+the	O
+value	O
+of	O
+these	O
+models	O
+for	O
+further	O
+studying	O
+the	O
+pathophysiology	O
+of	O
+LIDs	B-Disease
+.	O
+
+A	O
+diet	O
+promoting	O
+sugar	B-Disease
+dependency	I-Disease
+causes	O
+behavioral	B-Disease
+cross	I-Disease
+-	I-Disease
+sensitization	I-Disease
+to	O
+a	O
+low	O
+dose	O
+of	O
+amphetamine	B-Chemical
+.	O
+
+Previous	O
+research	O
+in	O
+this	O
+laboratory	O
+has	O
+shown	O
+that	O
+a	O
+diet	O
+of	O
+intermittent	O
+excessive	O
+sugar	O
+consumption	O
+produces	O
+a	O
+state	O
+with	O
+neurochemical	O
+and	O
+behavioral	O
+similarities	O
+to	O
+drug	B-Disease
+dependency	I-Disease
+.	O
+
+The	O
+present	O
+study	O
+examined	O
+whether	O
+female	O
+rats	O
+on	O
+various	O
+regimens	O
+of	O
+sugar	O
+access	O
+would	O
+show	O
+behavioral	B-Disease
+cross	I-Disease
+-	I-Disease
+sensitization	I-Disease
+to	O
+a	O
+low	O
+dose	O
+of	O
+amphetamine	B-Chemical
+.	O
+
+After	O
+a	O
+30	O
+-	O
+min	O
+baseline	O
+measure	O
+of	O
+locomotor	O
+activity	O
+(	O
+day	O
+0	O
+)	O
+,	O
+animals	O
+were	O
+maintained	O
+on	O
+a	O
+cyclic	O
+diet	O
+of	O
+12	O
+-	O
+h	O
+deprivation	O
+followed	O
+by	O
+12	O
+-	O
+h	O
+access	O
+to	O
+10	O
+%	O
+sucrose	B-Chemical
+solution	O
+and	O
+chow	O
+pellets	O
+(	O
+12	O
+h	O
+access	O
+starting	O
+4	O
+h	O
+after	O
+onset	O
+of	O
+the	O
+dark	O
+period	O
+)	O
+for	O
+21	O
+days	O
+.	O
+
+Locomotor	O
+activity	O
+was	O
+measured	O
+again	O
+for	O
+30	O
+min	O
+at	O
+the	O
+beginning	O
+of	O
+days	O
+1	O
+and	O
+21	O
+of	O
+sugar	O
+access	O
+.	O
+
+Beginning	O
+on	O
+day	O
+22	O
+,	O
+all	O
+rats	O
+were	O
+maintained	O
+on	O
+ad	O
+libitum	O
+chow	O
+.	O
+
+Nine	O
+days	O
+later	O
+locomotor	O
+activity	O
+was	O
+measured	O
+in	O
+response	O
+to	O
+a	O
+single	O
+low	O
+dose	O
+of	O
+amphetamine	B-Chemical
+(	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+The	O
+animals	O
+that	O
+had	O
+experienced	O
+cyclic	O
+sucrose	B-Chemical
+and	O
+chow	O
+were	O
+hyperactive	B-Disease
+in	O
+response	O
+to	O
+amphetamine	B-Chemical
+compared	O
+with	O
+four	O
+control	O
+groups	O
+(	O
+ad	O
+libitum	O
+10	O
+%	O
+sucrose	B-Chemical
+and	O
+chow	O
+followed	O
+by	O
+amphetamine	B-Chemical
+injection	O
+,	O
+cyclic	O
+chow	O
+followed	O
+by	O
+amphetamine	B-Chemical
+injection	O
+,	O
+ad	O
+libitum	O
+chow	O
+with	O
+amphetamine	B-Chemical
+,	O
+or	O
+cyclic	O
+10	O
+%	O
+sucrose	B-Chemical
+and	O
+chow	O
+with	O
+a	O
+saline	O
+injection	O
+)	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+a	O
+diet	O
+comprised	O
+of	O
+alternating	O
+deprivation	O
+and	O
+access	O
+to	O
+a	O
+sugar	O
+solution	O
+and	O
+chow	O
+produces	O
+bingeing	O
+on	O
+sugar	O
+that	O
+leads	O
+to	O
+a	O
+long	O
+lasting	O
+state	O
+of	O
+increased	O
+sensitivity	O
+to	O
+amphetamine	B-Chemical
+,	O
+possibly	O
+due	O
+to	O
+a	O
+lasting	O
+alteration	O
+in	O
+the	O
+dopamine	B-Chemical
+system	O
+.	O
+
+Reversible	O
+dilated	B-Disease
+cardiomyopathy	I-Disease
+related	O
+to	O
+amphotericin	B-Chemical
+B	I-Chemical
+therapy	O
+.	O
+
+We	O
+describe	O
+a	O
+patient	O
+who	O
+developed	O
+dilated	B-Disease
+cardiomyopathy	I-Disease
+and	O
+clinical	O
+congestive	O
+heart	B-Disease
+failure	I-Disease
+after	O
+2	O
+months	O
+of	O
+therapy	O
+with	O
+amphotericin	B-Chemical
+B	I-Chemical
+(	O
+AmB	B-Chemical
+)	O
+for	O
+disseminated	O
+coccidioidomycosis	B-Disease
+.	O
+
+His	O
+echocardiographic	O
+abnormalities	O
+and	O
+heart	B-Disease
+failure	I-Disease
+resolved	O
+after	O
+posaconazole	B-Chemical
+was	O
+substituted	O
+for	O
+AmB	B-Chemical
+.	O
+
+It	O
+is	O
+important	O
+to	O
+recognize	O
+the	O
+rare	O
+and	O
+potentially	O
+reversible	O
+toxicity	B-Disease
+of	O
+AmB	B-Chemical
+.	O
+
+NO	B-Chemical
+-	O
+induced	O
+migraine	B-Disease
+attack	O
+:	O
+strong	O
+increase	O
+in	O
+plasma	O
+calcitonin	B-Chemical
+gene	I-Chemical
+-	I-Chemical
+related	I-Chemical
+peptide	I-Chemical
+(	O
+CGRP	B-Chemical
+)	O
+concentration	O
+and	O
+negative	O
+correlation	O
+with	O
+platelet	O
+serotonin	B-Chemical
+release	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+investigate	O
+changes	O
+in	O
+the	O
+plasma	O
+calcitonin	B-Chemical
+gene	I-Chemical
+-	I-Chemical
+related	I-Chemical
+peptide	I-Chemical
+(	O
+CGRP	B-Chemical
+)	O
+concentration	O
+and	O
+platelet	O
+serotonin	B-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+hydroxytriptamine	I-Chemical
+,	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+)	O
+content	O
+during	O
+the	O
+immediate	O
+headache	B-Disease
+and	O
+the	O
+delayed	O
+genuine	O
+migraine	B-Disease
+attack	O
+provoked	O
+by	O
+nitroglycerin	B-Chemical
+.	O
+
+Fifteen	O
+female	O
+migraineurs	B-Disease
+(	I-Disease
+without	I-Disease
+aura	I-Disease
+)	I-Disease
+and	O
+eight	O
+controls	O
+participated	O
+in	O
+the	O
+study	O
+.	O
+
+Sublingual	O
+nitroglycerin	B-Chemical
+(	O
+0	O
+.	O
+5	O
+mg	O
+)	O
+was	O
+administered	O
+.	O
+
+Blood	O
+was	O
+collected	O
+from	O
+the	O
+antecubital	O
+vein	O
+four	O
+times	O
+:	O
+60	O
+min	O
+before	O
+and	O
+after	O
+the	O
+nitroglycerin	B-Chemical
+application	O
+,	O
+and	O
+60	O
+and	O
+120	O
+min	O
+after	O
+the	O
+beginning	O
+of	O
+the	O
+migraine	B-Disease
+attack	O
+(	O
+mean	O
+344	O
+and	O
+404	O
+min	O
+;	O
+12	O
+subjects	O
+)	O
+.	O
+
+In	O
+those	O
+subjects	O
+who	O
+had	O
+no	O
+migraine	B-Disease
+attack	O
+(	O
+11	O
+subjects	O
+)	O
+a	O
+similar	O
+time	O
+schedule	O
+was	O
+used	O
+.	O
+
+Plasma	O
+CGRP	B-Chemical
+concentration	O
+increased	O
+significantly	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+during	O
+the	O
+migraine	B-Disease
+attack	O
+and	O
+returned	O
+to	O
+baseline	O
+after	O
+the	O
+cessation	O
+of	O
+the	O
+migraine	B-Disease
+.	O
+
+In	O
+addition	O
+,	O
+both	O
+change	O
+and	O
+peak	O
+,	O
+showed	O
+significant	O
+positive	O
+correlations	O
+with	O
+migraine	B-Disease
+headache	B-Disease
+intensity	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+However	O
+,	O
+plasma	O
+CGRP	B-Chemical
+concentrations	O
+failed	O
+to	O
+change	O
+during	O
+immediate	O
+headache	B-Disease
+and	O
+in	O
+the	O
+subjects	O
+with	O
+no	O
+migraine	B-Disease
+attack	O
+.	O
+
+Basal	O
+CGRP	B-Chemical
+concentration	O
+was	O
+significantly	O
+higher	O
+and	O
+platelet	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+content	O
+tended	O
+to	O
+be	O
+lower	O
+in	O
+subjects	O
+who	O
+experienced	O
+a	O
+migraine	B-Disease
+attack	O
+.	O
+
+Platelet	O
+serotonin	B-Chemical
+content	O
+decreased	O
+significantly	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+after	O
+nitroglycerin	B-Chemical
+in	O
+subjects	O
+with	O
+no	O
+migraine	B-Disease
+attack	O
+but	O
+no	O
+consistent	O
+change	O
+was	O
+observed	O
+in	O
+patients	O
+with	O
+migraine	B-Disease
+attack	O
+.	O
+
+In	O
+conclusion	O
+,	O
+the	O
+fact	O
+that	O
+plasma	O
+CGRP	B-Chemical
+concentration	O
+correlates	O
+with	O
+the	O
+timing	O
+and	O
+severity	O
+of	O
+a	O
+migraine	B-Disease
+headache	B-Disease
+suggests	O
+a	O
+direct	O
+relationship	O
+between	O
+CGRP	B-Chemical
+and	O
+migraine	B-Disease
+.	O
+
+In	O
+contrast	O
+,	O
+serotonin	B-Chemical
+release	O
+from	O
+platelets	O
+does	O
+not	O
+provoke	O
+migraine	B-Disease
+,	O
+it	O
+may	O
+even	O
+counteract	O
+the	O
+headache	B-Disease
+and	O
+the	O
+concomitant	O
+CGRP	B-Chemical
+release	O
+in	O
+this	O
+model	O
+.	O
+
+Hyperbaric	O
+oxygen	B-Chemical
+therapy	O
+for	O
+control	O
+of	O
+intractable	O
+cyclophosphamide	B-Chemical
+-	O
+induced	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+intractable	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+due	O
+to	O
+cyclophosphamide	B-Chemical
+therapy	O
+for	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+.	O
+
+Conservative	O
+treatment	O
+,	O
+including	O
+bladder	O
+irrigation	O
+with	O
+physiological	O
+saline	O
+and	O
+instillation	O
+of	O
+prostaglandin	B-Chemical
+F2	I-Chemical
+alpha	I-Chemical
+,	O
+failed	O
+to	O
+totally	O
+control	O
+hemorrhage	B-Disease
+.	O
+
+We	O
+then	O
+used	O
+hyperbaric	O
+oxygen	B-Chemical
+at	O
+an	O
+absolute	O
+pressure	O
+of	O
+2	O
+atm	O
+,	O
+5	O
+days	O
+a	O
+week	O
+for	O
+8	O
+consecutive	O
+weeks	O
+.	O
+
+The	O
+bleeding	B-Disease
+ceased	O
+completely	O
+by	O
+the	O
+end	O
+of	O
+treatment	O
+and	O
+the	O
+patient	O
+remained	O
+free	O
+of	O
+hematuria	B-Disease
+thereafter	O
+.	O
+
+No	O
+side	O
+effect	O
+was	O
+noted	O
+during	O
+the	O
+course	O
+of	O
+therapy	O
+.	O
+
+In	O
+future	O
+,	O
+this	O
+form	O
+of	O
+therapy	O
+can	O
+offer	O
+a	O
+safe	O
+alternative	O
+in	O
+the	O
+treatment	O
+of	O
+cyclophosphamide	B-Chemical
+-	O
+induced	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+.	O
+
+Acute	B-Disease
+psychosis	I-Disease
+due	O
+to	O
+treatment	O
+with	O
+phenytoin	B-Chemical
+in	O
+a	O
+nonepileptic	O
+patient	O
+.	O
+
+The	O
+development	O
+of	O
+psychosis	B-Disease
+related	O
+to	O
+antiepileptic	O
+drug	O
+treatment	O
+is	O
+usually	O
+attributed	O
+to	O
+the	O
+interaction	O
+between	O
+the	O
+epileptic	B-Disease
+brain	O
+substratum	O
+and	O
+the	O
+antiepileptic	O
+drugs	O
+.	O
+
+The	O
+case	O
+of	O
+a	O
+nonepileptic	O
+patient	O
+who	O
+developed	O
+psychosis	B-Disease
+following	O
+phenytoin	B-Chemical
+treatment	O
+for	O
+trigeminal	B-Disease
+neuralgia	I-Disease
+is	O
+described	O
+.	O
+
+This	O
+case	O
+suggests	O
+that	O
+the	O
+psychotic	B-Disease
+symptoms	I-Disease
+that	O
+occur	O
+following	O
+phenytoin	B-Chemical
+treatment	O
+in	O
+some	O
+epileptic	B-Disease
+patients	O
+may	O
+be	O
+the	O
+direct	O
+result	O
+of	O
+medication	O
+,	O
+unrelated	O
+to	O
+seizures	B-Disease
+.	O
+
+Risks	O
+of	O
+the	O
+consumption	O
+of	O
+beverages	O
+containing	O
+quinine	B-Chemical
+.	O
+
+Although	O
+the	O
+United	O
+States	O
+Food	O
+and	O
+Drug	O
+Administration	O
+banned	O
+its	O
+use	O
+for	O
+nocturnal	B-Disease
+leg	I-Disease
+cramps	I-Disease
+due	O
+to	O
+lack	O
+of	O
+safety	O
+and	O
+efficacy	O
+,	O
+quinine	B-Chemical
+is	O
+widely	O
+available	O
+in	O
+beverages	O
+including	O
+tonic	O
+water	O
+and	O
+bitter	O
+lemon	O
+.	O
+
+Numerous	O
+anecdotal	O
+reports	O
+suggest	O
+that	O
+products	O
+containing	O
+quinine	B-Chemical
+may	O
+produce	O
+neurological	B-Disease
+complications	I-Disease
+,	O
+including	O
+confusion	B-Disease
+,	O
+altered	O
+mental	O
+status	O
+,	O
+seizures	B-Disease
+,	O
+and	O
+coma	B-Disease
+,	O
+particularly	O
+in	O
+older	O
+women	O
+.	O
+
+Psychologists	O
+need	O
+to	O
+inquire	O
+about	O
+consumption	O
+of	O
+quinine	B-Chemical
+-	O
+containing	O
+beverages	O
+as	O
+part	O
+of	O
+an	O
+evaluation	O
+process	O
+.	O
+
+Transient	O
+platypnea	B-Disease
+-	I-Disease
+orthodeoxia	I-Disease
+-	I-Disease
+like	I-Disease
+syndrome	I-Disease
+induced	O
+by	O
+propafenone	B-Chemical
+overdose	B-Disease
+in	O
+a	O
+young	O
+woman	O
+with	O
+Ebstein	B-Disease
+'	I-Disease
+s	I-Disease
+anomaly	I-Disease
+.	O
+
+In	O
+this	O
+report	O
+we	O
+describe	O
+the	O
+case	O
+of	O
+a	O
+37	O
+-	O
+year	O
+-	O
+old	O
+white	O
+woman	O
+with	O
+Ebstein	B-Disease
+'	I-Disease
+s	I-Disease
+anomaly	I-Disease
+,	O
+who	O
+developed	O
+a	O
+rare	O
+syndrome	O
+called	O
+platypnea	B-Disease
+-	I-Disease
+orthodeoxia	I-Disease
+,	O
+characterized	O
+by	O
+massive	O
+right	O
+-	O
+to	O
+-	O
+left	O
+interatrial	O
+shunting	O
+with	O
+transient	O
+profound	O
+hypoxia	B-Disease
+and	O
+cyanosis	B-Disease
+.	O
+
+This	O
+shunt	O
+of	O
+blood	O
+via	O
+a	O
+patent	B-Disease
+foramen	I-Disease
+ovale	I-Disease
+occurred	O
+in	O
+the	O
+presence	O
+of	O
+a	O
+normal	O
+pulmonary	O
+artery	O
+pressure	O
+,	O
+and	O
+was	O
+probably	O
+precipitated	O
+by	O
+a	O
+propafenone	B-Chemical
+overdose	B-Disease
+.	O
+
+This	O
+drug	O
+caused	O
+biventricular	B-Disease
+dysfunction	I-Disease
+,	O
+due	O
+to	O
+its	O
+negative	O
+inotropic	O
+effect	O
+,	O
+and	O
+hypotension	B-Disease
+,	O
+due	O
+to	O
+its	O
+peripheral	O
+vasodilatory	O
+effect	O
+.	O
+
+These	O
+effects	O
+gave	O
+rise	O
+to	O
+an	O
+increase	O
+in	O
+the	O
+right	O
+atrial	O
+pressure	O
+and	O
+a	O
+decrease	O
+in	O
+the	O
+left	O
+one	O
+with	O
+a	O
+consequent	O
+stretching	O
+of	O
+the	O
+foramen	O
+ovale	O
+and	O
+the	O
+creation	O
+of	O
+massive	O
+right	O
+-	O
+to	O
+-	O
+left	O
+shunting	O
+.	O
+
+In	O
+our	O
+case	O
+this	O
+interatrial	O
+shunt	O
+was	O
+very	O
+accurately	O
+detected	O
+at	O
+bubble	O
+contrast	O
+echocardiography	O
+.	O
+
+Noxious	O
+chemical	O
+stimulation	O
+of	O
+rat	O
+facial	O
+mucosa	O
+increases	O
+intracranial	O
+blood	O
+flow	O
+through	O
+a	O
+trigemino	O
+-	O
+parasympathetic	O
+reflex	O
+-	O
+-	O
+an	O
+experimental	O
+model	O
+for	O
+vascular	B-Disease
+dysfunctions	I-Disease
+in	O
+cluster	B-Disease
+headache	I-Disease
+.	O
+
+Cluster	B-Disease
+headache	I-Disease
+is	O
+characterized	O
+by	O
+typical	O
+autonomic	O
+dysfunctions	O
+including	O
+facial	O
+and	O
+intracranial	B-Disease
+vascular	I-Disease
+disturbances	I-Disease
+.	O
+
+Both	O
+the	O
+trigeminal	O
+and	O
+the	O
+cranial	O
+parasympathetic	O
+systems	O
+may	O
+be	O
+involved	O
+in	O
+mediating	O
+these	O
+dysfunctions	O
+.	O
+
+An	O
+experimental	O
+model	O
+was	O
+developed	O
+in	O
+the	O
+rat	O
+to	O
+measure	O
+changes	O
+in	O
+lacrimation	O
+and	O
+intracranial	O
+blood	O
+flow	O
+following	O
+noxious	O
+chemical	O
+stimulation	O
+of	O
+facial	O
+mucosa	O
+.	O
+
+Blood	O
+flow	O
+was	O
+monitored	O
+in	O
+arteries	O
+of	O
+the	O
+exposed	O
+cranial	O
+dura	O
+mater	O
+and	O
+the	O
+parietal	O
+cortex	O
+using	O
+laser	O
+Doppler	O
+flowmetry	O
+.	O
+
+Capsaicin	B-Chemical
+(	O
+0	O
+.	O
+01	O
+-	O
+1	O
+mm	O
+)	O
+applied	O
+to	O
+oral	O
+or	O
+nasal	O
+mucosa	O
+induced	O
+increases	B-Disease
+in	I-Disease
+dural	I-Disease
+and	I-Disease
+cortical	I-Disease
+blood	I-Disease
+flow	I-Disease
+and	O
+provoked	O
+lacrimation	O
+.	O
+
+These	O
+responses	O
+were	O
+blocked	O
+by	O
+systemic	O
+pre	O
+-	O
+administration	O
+of	O
+hexamethonium	B-Chemical
+chloride	I-Chemical
+(	O
+20	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+The	O
+evoked	O
+increases	B-Disease
+in	I-Disease
+dural	I-Disease
+blood	I-Disease
+flow	I-Disease
+were	O
+also	O
+abolished	O
+by	O
+topical	O
+pre	O
+-	O
+administration	O
+of	O
+atropine	B-Chemical
+(	O
+1	O
+mm	O
+)	O
+and	O
+[	O
+Lys1	O
+,	O
+Pro2	O
+,	O
+5	O
+,	O
+Arg3	O
+,	O
+4	O
+,	O
+Tyr6	O
+]	O
+-	O
+VIP	O
+(	O
+0	O
+.	O
+1	O
+mm	O
+)	O
+,	O
+a	O
+vasoactive	O
+intestinal	O
+polypeptide	O
+(	O
+VIP	O
+)	O
+antagonist	O
+,	O
+onto	O
+the	O
+exposed	O
+dura	O
+mater	O
+.	O
+
+We	O
+conclude	O
+that	O
+noxious	O
+stimulation	O
+of	O
+facial	O
+mucosa	O
+increases	O
+intracranial	O
+blood	O
+flow	O
+and	O
+lacrimation	O
+via	O
+a	O
+trigemino	O
+-	O
+parasympathetic	O
+reflex	O
+.	O
+
+The	O
+blood	O
+flow	O
+responses	O
+seem	O
+to	O
+be	O
+mediated	O
+by	O
+the	O
+release	O
+of	O
+acetylcholine	B-Chemical
+and	O
+VIP	O
+within	O
+the	O
+meninges	O
+.	O
+
+Similar	O
+mechanisms	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+pathogenesis	O
+of	O
+cluster	B-Disease
+headache	I-Disease
+.	O
+
+Organophosphate	B-Chemical
+-	O
+induced	O
+convulsions	B-Disease
+and	O
+prevention	O
+of	O
+neuropathological	B-Disease
+damages	I-Disease
+.	O
+
+Such	O
+organophosphorus	B-Chemical
+(	O
+OP	B-Chemical
+)	O
+compounds	O
+as	O
+diisopropylfluorophosphate	B-Chemical
+(	O
+DFP	B-Chemical
+)	O
+,	O
+sarin	B-Chemical
+and	O
+soman	B-Chemical
+are	O
+potent	O
+inhibitors	O
+of	O
+acetylcholinesterases	O
+(	O
+AChEs	O
+)	O
+and	O
+butyrylcholinesterases	O
+(	O
+BChEs	O
+)	O
+.	O
+
+The	O
+acute	O
+toxicity	B-Disease
+of	O
+OPs	B-Chemical
+is	O
+the	O
+result	O
+of	O
+their	O
+irreversible	O
+binding	O
+with	O
+AChEs	O
+in	O
+the	O
+central	O
+nervous	O
+system	O
+(	O
+CNS	O
+)	O
+,	O
+which	O
+elevates	O
+acetylcholine	B-Chemical
+(	O
+ACh	B-Chemical
+)	O
+levels	O
+.	O
+
+The	O
+protective	O
+action	O
+of	O
+subcutaneously	O
+(	O
+SC	O
+)	O
+administered	O
+antidotes	O
+or	O
+their	O
+combinations	O
+in	O
+DFP	B-Chemical
+(	O
+2	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+intoxication	O
+was	O
+studied	O
+in	O
+9	O
+-	O
+10	O
+-	O
+weeks	O
+-	O
+old	O
+Han	O
+-	O
+Wistar	O
+male	O
+rats	O
+.	O
+
+The	O
+rats	O
+received	O
+AChE	O
+reactivator	O
+pralidoxime	B-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+chloride	I-Chemical
+(	O
+2PAM	B-Chemical
+)	O
+(	O
+30	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+,	O
+anticonvulsant	O
+diazepam	B-Chemical
+(	O
+2	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+,	O
+A	O
+(	O
+1	O
+)	O
+-	O
+adenosine	B-Chemical
+receptor	O
+agonist	O
+N	B-Chemical
+(	I-Chemical
+6	I-Chemical
+)	I-Chemical
+-	I-Chemical
+cyclopentyl	I-Chemical
+adenosine	I-Chemical
+(	O
+CPA	B-Chemical
+)	O
+(	O
+2	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+,	O
+NMDA	B-Chemical
+-	O
+receptor	O
+antagonist	O
+dizocilpine	B-Chemical
+maleate	I-Chemical
+(	O
++	O
+-	O
+MK801	O
+hydrogen	O
+maleate	O
+)	O
+(	O
+2	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+or	O
+their	O
+combinations	O
+with	O
+cholinolytic	O
+drug	O
+atropine	B-Chemical
+sulfate	I-Chemical
+(	O
+50	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+BW	O
+)	O
+immediately	O
+or	O
+30	O
+min	O
+after	O
+the	O
+single	O
+SC	O
+injection	O
+of	O
+DFP	B-Chemical
+.	O
+
+The	O
+control	O
+rats	O
+received	O
+atropine	B-Chemical
+sulfate	I-Chemical
+,	O
+but	O
+also	O
+saline	O
+and	O
+olive	O
+oil	O
+instead	O
+of	O
+other	O
+antidotes	O
+and	O
+DFP	B-Chemical
+,	O
+respectively	O
+.	O
+
+All	O
+rats	O
+were	O
+terminated	O
+either	O
+24	O
+h	O
+or	O
+3	O
+weeks	O
+after	O
+the	O
+DFP	B-Chemical
+injection	O
+.	O
+
+The	O
+rats	O
+treated	O
+with	O
+DFP	B-Chemical
+-	O
+atropine	B-Chemical
+showed	O
+severe	O
+typical	O
+OP	B-Chemical
+-	O
+induced	O
+toxicity	B-Disease
+signs	O
+.	O
+
+When	O
+CPA	B-Chemical
+,	O
+diazepam	B-Chemical
+or	O
+2PAM	B-Chemical
+was	O
+given	O
+immediately	O
+after	O
+DFP	B-Chemical
+-	O
+atropine	B-Chemical
+,	O
+these	O
+treatments	O
+prevented	O
+,	O
+delayed	O
+or	O
+shortened	O
+the	O
+occurrence	O
+of	O
+serious	O
+signs	O
+of	O
+poisoning	B-Disease
+.	O
+
+Atropine	B-Chemical
+-	O
+MK801	B-Chemical
+did	O
+not	O
+offer	O
+any	O
+additional	O
+protection	O
+against	O
+DFP	B-Chemical
+toxicity	B-Disease
+.	O
+
+In	O
+conclusion	O
+,	O
+CPA	B-Chemical
+,	O
+diazepam	B-Chemical
+and	O
+2PAM	B-Chemical
+in	O
+combination	O
+with	O
+atropine	B-Chemical
+prevented	O
+the	O
+occurrence	O
+of	O
+serious	O
+signs	O
+of	O
+poisoning	B-Disease
+and	O
+thus	O
+reduced	O
+the	O
+toxicity	B-Disease
+of	O
+DFP	B-Chemical
+in	O
+rat	O
+.	O
+
+A	O
+pyridoxine	B-Chemical
+-	O
+dependent	O
+behavioral	B-Disease
+disorder	I-Disease
+unmasked	O
+by	O
+isoniazid	B-Chemical
+.	O
+
+A	O
+3	O
+-	O
+year	O
+-	O
+old	O
+girl	O
+had	O
+behavioral	B-Disease
+deterioration	I-Disease
+,	O
+with	O
+hyperkinesis	B-Disease
+,	O
+irritability	B-Disease
+,	O
+and	O
+sleeping	B-Disease
+difficulties	I-Disease
+after	O
+the	O
+therapeutic	O
+administration	O
+of	O
+isoniazid	B-Chemical
+.	O
+
+The	O
+administration	O
+of	O
+pharmacologic	O
+doses	O
+of	O
+pyridoxine	B-Chemical
+hydrochloride	I-Chemical
+led	O
+to	O
+a	O
+disappearance	O
+of	O
+symptoms	O
+.	O
+
+After	O
+discontinuing	O
+isoniazid	B-Chemical
+therapy	O
+a	O
+similar	O
+pattern	O
+of	O
+behavior	O
+was	O
+noted	O
+that	O
+was	O
+controlled	O
+by	O
+pyridoxine	B-Chemical
+.	O
+
+A	O
+placebo	O
+had	O
+no	O
+effect	O
+,	O
+but	O
+niacinamide	B-Chemical
+was	O
+as	O
+effective	O
+as	O
+pyridoxine	B-Chemical
+.	O
+
+Periodic	O
+withdrawal	O
+of	O
+pyridoxine	B-Chemical
+was	O
+associated	O
+with	O
+return	O
+of	O
+the	O
+hyperkinesis	B-Disease
+.	O
+
+The	O
+level	O
+of	O
+pyridoxal	B-Chemical
+in	O
+the	O
+blood	O
+was	O
+normal	O
+during	O
+the	O
+periods	O
+of	O
+relapse	O
+.	O
+
+Metabolic	O
+studies	O
+suggested	O
+a	O
+block	O
+in	O
+the	O
+kynurenine	B-Chemical
+pathway	O
+of	O
+tryptophan	B-Chemical
+metabolism	O
+.	O
+
+The	O
+patient	O
+has	O
+been	O
+followed	O
+for	O
+six	O
+years	O
+and	O
+has	O
+required	O
+pharmacologic	O
+doses	O
+of	O
+pyridoxine	B-Chemical
+to	O
+control	O
+her	O
+behavior	O
+.	O
+
+Recurrent	O
+excitation	O
+in	O
+the	O
+dentate	O
+gyrus	O
+of	O
+a	O
+murine	O
+model	O
+of	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+.	O
+
+Similar	O
+to	O
+rats	O
+,	O
+systemic	O
+pilocarpine	B-Chemical
+injection	O
+causes	O
+status	B-Disease
+epilepticus	I-Disease
+(	O
+SE	B-Disease
+)	O
+and	O
+the	O
+eventual	O
+development	O
+of	O
+spontaneous	O
+seizures	B-Disease
+and	O
+mossy	O
+fiber	O
+sprouting	O
+in	O
+C57BL	O
+/	O
+6	O
+and	O
+CD1	O
+mice	O
+,	O
+but	O
+the	O
+physiological	O
+correlates	O
+of	O
+these	O
+events	O
+have	O
+not	O
+been	O
+identified	O
+in	O
+mice	O
+.	O
+
+Population	O
+responses	O
+in	O
+granule	O
+cells	O
+of	O
+the	O
+dentate	O
+gyrus	O
+were	O
+examined	O
+in	O
+transverse	O
+slices	O
+of	O
+the	O
+ventral	O
+hippocampus	O
+from	O
+pilocarpine	B-Chemical
+-	O
+treated	O
+and	O
+untreated	O
+mice	O
+.	O
+
+In	O
+Mg	B-Chemical
+(	O
+2	O
++	O
+)	O
+-	O
+free	O
+bathing	O
+medium	O
+containing	O
+bicuculline	B-Chemical
+,	O
+conditions	O
+designed	O
+to	O
+increase	O
+excitability	O
+in	O
+the	O
+slices	O
+,	O
+electrical	O
+stimulation	O
+of	O
+the	O
+hilus	O
+resulted	O
+in	O
+a	O
+single	O
+population	O
+spike	O
+in	O
+granule	O
+cells	O
+from	O
+control	O
+mice	O
+and	O
+pilocarpine	B-Chemical
+-	O
+treated	O
+mice	O
+that	O
+did	O
+not	O
+experience	O
+SE	B-Disease
+.	O
+
+In	O
+SE	B-Disease
+survivors	O
+,	O
+similar	O
+stimulation	O
+resulted	O
+in	O
+a	O
+population	O
+spike	O
+followed	O
+,	O
+at	O
+a	O
+variable	O
+latency	O
+,	O
+by	O
+negative	O
+DC	O
+shifts	O
+and	O
+repetitive	O
+afterdischarges	O
+of	O
+3	O
+-	O
+60	O
+s	O
+duration	O
+,	O
+which	O
+were	O
+blocked	O
+by	O
+ionotropic	O
+glutamate	B-Chemical
+receptor	O
+antagonists	O
+.	O
+
+Focal	O
+glutamate	B-Chemical
+photostimulation	O
+of	O
+the	O
+granule	O
+cell	O
+layer	O
+at	O
+sites	O
+distant	O
+from	O
+the	O
+recording	O
+pipette	O
+resulted	O
+in	O
+population	O
+responses	O
+of	O
+1	O
+-	O
+30	O
+s	O
+duration	O
+in	O
+slices	O
+from	O
+SE	B-Disease
+survivors	O
+but	O
+not	O
+other	O
+groups	O
+.	O
+
+These	O
+data	O
+support	O
+the	O
+hypothesis	O
+that	O
+SE	B-Disease
+-	O
+induced	O
+mossy	O
+fiber	O
+sprouting	O
+and	O
+synaptic	O
+reorganization	O
+are	O
+relevant	O
+characteristics	O
+of	O
+seizure	B-Disease
+development	O
+in	O
+these	O
+murine	O
+strains	O
+,	O
+resembling	O
+rat	O
+models	O
+of	O
+human	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+.	O
+
+Urinary	B-Disease
+bladder	I-Disease
+cancer	I-Disease
+in	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+:	O
+risks	O
+and	O
+relation	O
+to	O
+cyclophosphamide	B-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+assess	O
+and	O
+characterise	O
+the	O
+risk	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+,	O
+and	O
+its	O
+relation	O
+to	O
+cyclophosphamide	B-Chemical
+,	O
+in	O
+patients	O
+with	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+.	O
+
+METHODS	O
+:	O
+In	O
+the	O
+population	O
+based	O
+,	O
+nationwide	O
+Swedish	O
+Inpatient	O
+Register	O
+a	O
+cohort	O
+of	O
+1065	O
+patients	O
+with	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+,	O
+1969	O
+-	O
+95	O
+,	O
+was	O
+identified	O
+.	O
+
+Through	O
+linkage	O
+with	O
+the	O
+Swedish	O
+Cancer	B-Disease
+Register	O
+,	O
+all	O
+subjects	O
+in	O
+this	O
+cohort	O
+diagnosed	O
+with	O
+bladder	B-Disease
+cancer	I-Disease
+were	O
+identified	O
+.	O
+
+Nested	O
+within	O
+the	O
+cohort	O
+,	O
+a	O
+matched	O
+case	O
+-	O
+control	O
+study	O
+was	O
+performed	O
+to	O
+estimate	O
+the	O
+association	O
+between	O
+cyclophosphamide	B-Chemical
+and	O
+bladder	B-Disease
+cancer	I-Disease
+using	O
+odds	O
+ratios	O
+(	O
+ORs	O
+)	O
+as	O
+relative	O
+risk	O
+.	O
+
+In	O
+the	O
+cohort	O
+the	O
+cumulative	O
+risk	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+after	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+,	O
+and	O
+the	O
+relative	O
+prevalence	O
+of	O
+a	O
+history	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+at	O
+the	O
+time	O
+of	O
+diagnosis	O
+of	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+,	O
+were	O
+also	O
+estimated	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+median	O
+cumulative	O
+doses	O
+of	O
+cyclophosphamide	B-Chemical
+among	O
+cases	O
+(	O
+n	O
+=	O
+11	O
+)	O
+and	O
+controls	O
+(	O
+n	O
+=	O
+25	O
+)	O
+were	O
+113	O
+g	O
+and	O
+25	O
+g	O
+,	O
+respectively	O
+.	O
+
+The	O
+risk	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+doubled	O
+for	O
+every	O
+10	O
+g	O
+increment	O
+in	O
+cyclophosphamide	B-Chemical
+(	O
+OR	O
+=	O
+2	O
+.	O
+0	O
+,	O
+95	O
+%	O
+confidence	O
+interval	O
+(	O
+CI	O
+)	O
+0	O
+.	O
+8	O
+to	O
+4	O
+.	O
+9	O
+)	O
+.	O
+
+Treatment	O
+duration	O
+longer	O
+than	O
+1	O
+year	O
+was	O
+associated	O
+with	O
+an	O
+eightfold	O
+increased	O
+risk	O
+(	O
+OR	O
+=	O
+7	O
+.	O
+7	O
+,	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+9	O
+to	O
+69	O
+)	O
+.	O
+
+The	O
+absolute	O
+risk	O
+for	O
+bladder	B-Disease
+cancer	I-Disease
+in	O
+the	O
+cohort	O
+reached	O
+10	O
+%	O
+16	O
+years	O
+after	O
+diagnosis	O
+of	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+,	O
+and	O
+a	O
+history	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+was	O
+(	O
+non	O
+-	O
+significantly	O
+)	O
+twice	O
+as	O
+common	O
+as	O
+expected	O
+at	O
+the	O
+time	O
+of	O
+diagnosis	O
+of	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+results	O
+indicate	O
+a	O
+dose	O
+-	O
+response	O
+relationship	O
+between	O
+cyclophosphamide	B-Chemical
+and	O
+the	O
+risk	O
+of	O
+bladder	B-Disease
+cancer	I-Disease
+,	O
+high	O
+cumulative	O
+risks	O
+in	O
+the	O
+entire	O
+cohort	O
+,	O
+and	O
+also	O
+the	O
+possibility	O
+of	O
+risk	O
+factors	O
+operating	O
+even	O
+before	O
+Wegener	B-Disease
+'	I-Disease
+s	I-Disease
+granulomatosis	I-Disease
+.	O
+
+Differential	O
+modulation	O
+by	O
+estrogen	B-Chemical
+of	O
+alpha2	O
+-	O
+adrenergic	O
+and	O
+I1	O
+-	O
+imidazoline	B-Chemical
+receptor	O
+-	O
+mediated	O
+hypotension	B-Disease
+in	O
+female	O
+rats	O
+.	O
+
+We	O
+have	O
+recently	O
+shown	O
+that	O
+estrogen	B-Chemical
+negatively	O
+modulates	O
+the	O
+hypotensive	B-Disease
+effect	O
+of	O
+clonidine	B-Chemical
+(	O
+mixed	O
+alpha2	O
+-	O
+/	O
+I1	O
+-	O
+receptor	O
+agonist	O
+)	O
+in	O
+female	O
+rats	O
+and	O
+implicates	O
+the	O
+cardiovascular	O
+autonomic	O
+control	O
+in	O
+this	O
+interaction	O
+.	O
+
+The	O
+present	O
+study	O
+investigated	O
+whether	O
+this	O
+effect	O
+of	O
+estrogen	B-Chemical
+involves	O
+interaction	O
+with	O
+alpha2	O
+-	O
+and	O
+/	O
+or	O
+I1	O
+-	O
+receptors	O
+.	O
+
+Changes	O
+evoked	O
+by	O
+a	O
+single	O
+intraperitoneal	O
+injection	O
+of	O
+rilmenidine	B-Chemical
+(	O
+600	O
+microg	O
+/	O
+kg	O
+)	O
+or	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+(	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+selective	O
+I1	O
+-	O
+and	O
+alpha2	O
+-	O
+receptor	O
+agonists	O
+,	O
+respectively	O
+,	O
+in	O
+blood	O
+pressure	O
+,	O
+hemodynamic	O
+variability	O
+,	O
+and	O
+locomotor	O
+activity	O
+were	O
+assessed	O
+in	O
+radiotelemetered	O
+sham	O
+-	O
+operated	O
+and	O
+ovariectomized	O
+(	O
+Ovx	O
+)	O
+Sprague	O
+-	O
+Dawley	O
+female	O
+rats	O
+with	O
+or	O
+without	O
+12	O
+-	O
+wk	O
+estrogen	B-Chemical
+replacement	O
+.	O
+
+Three	O
+time	O
+domain	O
+indexes	O
+of	O
+hemodynamic	O
+variability	O
+were	O
+employed	O
+:	O
+the	O
+standard	O
+deviation	O
+of	O
+mean	O
+arterial	O
+pressure	O
+as	O
+a	O
+measure	O
+of	O
+blood	O
+pressure	O
+variability	O
+and	O
+the	O
+standard	O
+deviation	O
+of	O
+beat	O
+-	O
+to	O
+-	O
+beat	O
+intervals	O
+(	O
+SDRR	O
+)	O
+and	O
+the	O
+root	O
+mean	O
+square	O
+of	O
+successive	O
+differences	O
+in	O
+R	O
+-	O
+wave	O
+-	O
+to	O
+-	O
+R	O
+-	O
+wave	O
+intervals	O
+as	O
+measures	O
+of	O
+heart	O
+rate	O
+variability	O
+.	O
+
+In	O
+sham	O
+-	O
+operated	O
+rats	O
+,	O
+rilmenidine	B-Chemical
+or	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+elicited	O
+similar	O
+hypotension	B-Disease
+that	O
+lasted	O
+at	O
+least	O
+5	O
+h	O
+and	O
+was	O
+associated	O
+with	O
+reductions	O
+in	O
+standard	O
+deviation	O
+of	O
+mean	O
+arterial	O
+pressure	O
+.	O
+
+SDRR	O
+was	O
+reduced	O
+only	O
+by	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+.	O
+
+Ovx	O
+significantly	O
+enhanced	O
+the	O
+hypotensive	B-Disease
+response	O
+to	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+,	O
+in	O
+contrast	O
+to	O
+no	O
+effect	O
+on	O
+rilmenidine	B-Chemical
+hypotension	B-Disease
+.	O
+
+The	O
+enhanced	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+hypotension	B-Disease
+in	O
+Ovx	O
+rats	O
+was	O
+paralleled	O
+with	O
+further	O
+reduction	O
+in	O
+SDRR	O
+and	O
+a	B-Disease
+reduced	I-Disease
+locomotor	I-Disease
+activity	I-Disease
+.	O
+
+Estrogen	O
+replacement	O
+(	O
+17beta	B-Chemical
+-	I-Chemical
+estradiol	I-Chemical
+subcutaneous	O
+pellet	O
+,	O
+14	O
+.	O
+2	O
+microg	O
+/	O
+day	O
+,	O
+12	O
+wk	O
+)	O
+of	O
+Ovx	O
+rats	O
+restored	O
+the	O
+hemodynamic	O
+and	O
+locomotor	O
+effects	O
+of	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+to	O
+sham	O
+-	O
+operated	O
+levels	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+estrogen	B-Chemical
+downregulates	O
+alpha2	O
+-	O
+but	O
+not	O
+I1	O
+-	O
+receptor	O
+-	O
+mediated	O
+hypotension	B-Disease
+and	O
+highlight	O
+a	O
+role	O
+for	O
+the	O
+cardiac	O
+autonomic	O
+control	O
+in	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+-	O
+estrogen	B-Chemical
+interaction	O
+.	O
+
+Severe	O
+reversible	O
+left	B-Disease
+ventricular	I-Disease
+systolic	I-Disease
+and	I-Disease
+diastolic	I-Disease
+dysfunction	I-Disease
+due	O
+to	O
+accidental	O
+iatrogenic	O
+epinephrine	B-Chemical
+overdose	B-Disease
+.	O
+
+Catecholamine	B-Chemical
+-	O
+induced	O
+cardiomyopathy	B-Disease
+due	O
+to	O
+chronic	O
+excess	O
+of	O
+endogenous	O
+catecholamines	B-Chemical
+has	O
+been	O
+recognized	O
+for	O
+decades	O
+as	O
+a	O
+clinical	O
+phenomenon	O
+.	O
+
+In	O
+contrast	O
+,	O
+reports	O
+of	O
+myocardial	B-Disease
+dysfunction	I-Disease
+due	O
+to	O
+acute	O
+iatrogenic	O
+overdose	B-Disease
+are	O
+rare	O
+.	O
+
+A	O
+35	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+whose	O
+cervix	O
+uteri	O
+was	O
+inadvertently	O
+injected	O
+with	O
+8	O
+mg	O
+of	O
+epinephrine	B-Chemical
+developed	O
+myocardial	B-Disease
+stunning	I-Disease
+that	O
+was	O
+characterized	O
+by	O
+severe	O
+hemodynamic	O
+compromise	O
+,	O
+profound	O
+,	O
+albeit	O
+transient	O
+,	O
+left	B-Disease
+ventricular	I-Disease
+systolic	I-Disease
+and	I-Disease
+diastolic	I-Disease
+dysfunction	I-Disease
+,	O
+and	O
+only	O
+modestly	O
+elevated	O
+biochemical	O
+markers	O
+of	O
+myocardial	B-Disease
+necrosis	I-Disease
+.	O
+
+Our	O
+case	O
+illustrates	O
+the	O
+serious	O
+consequences	O
+of	O
+medical	O
+errors	O
+that	O
+can	O
+be	O
+avoided	O
+through	O
+improved	O
+medication	O
+labeling	O
+and	O
+staff	O
+supervision	O
+.	O
+
+Cardioprotective	O
+effect	O
+of	O
+tincture	B-Chemical
+of	I-Chemical
+Crataegus	I-Chemical
+on	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Tincture	B-Chemical
+of	I-Chemical
+Crataegus	I-Chemical
+(	O
+TCR	B-Chemical
+)	O
+,	O
+an	O
+alcoholic	B-Chemical
+extract	I-Chemical
+of	I-Chemical
+the	I-Chemical
+berries	I-Chemical
+of	I-Chemical
+hawthorn	I-Chemical
+(	O
+Crataegus	B-Chemical
+oxycantha	I-Chemical
+)	O
+,	O
+is	O
+used	O
+in	O
+herbal	O
+and	O
+homeopathic	O
+medicine	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+done	O
+to	O
+investigate	O
+the	O
+protective	O
+effect	O
+of	O
+TCR	B-Chemical
+on	O
+experimentally	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Pretreatment	O
+of	O
+TCR	B-Chemical
+,	O
+at	O
+a	O
+dose	O
+of	O
+0	O
+.	O
+5	O
+mL	O
+/	O
+100	O
+g	O
+bodyweight	O
+per	O
+day	O
+,	O
+orally	O
+for	O
+30	O
+days	O
+,	O
+prevented	O
+the	O
+increase	O
+in	O
+lipid	O
+peroxidation	O
+and	O
+activity	O
+of	O
+marker	O
+enzymes	O
+observed	O
+in	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+rats	O
+(	O
+85	O
+mg	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+s	O
+.	O
+c	O
+.	O
+for	O
+2	O
+days	O
+at	O
+an	O
+interval	O
+of	O
+24	O
+h	O
+)	O
+.	O
+
+TCR	B-Chemical
+prevented	O
+the	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+decrease	O
+in	O
+antioxidant	O
+enzymes	O
+in	O
+the	O
+heart	O
+and	O
+increased	O
+the	O
+rate	O
+of	O
+ADP	B-Chemical
+-	O
+stimulated	O
+oxygen	B-Chemical
+uptake	O
+and	O
+respiratory	O
+coupling	O
+ratio	O
+.	O
+
+TCR	B-Chemical
+protected	O
+against	O
+pathological	O
+changes	O
+induced	O
+by	O
+isoproterenol	B-Chemical
+in	O
+rat	O
+heart	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+pretreatment	O
+with	O
+TCR	B-Chemical
+may	O
+be	O
+useful	O
+in	O
+preventing	O
+the	O
+damage	O
+induced	O
+by	O
+isoproterenol	B-Chemical
+in	O
+rat	O
+heart	O
+.	O
+
+Treatment	O
+of	O
+tinnitus	B-Disease
+by	O
+intratympanic	O
+instillation	O
+of	O
+lignocaine	B-Chemical
+(	O
+lidocaine	B-Chemical
+)	O
+2	O
+per	O
+cent	O
+through	O
+ventilation	O
+tubes	O
+.	O
+
+Idiopathic	B-Disease
+subjective	I-Disease
+tinnitus	I-Disease
+(	O
+IST	B-Disease
+)	O
+is	O
+one	O
+of	O
+the	O
+most	O
+obscure	O
+otological	O
+pathologies	O
+.	O
+
+This	O
+paper	O
+presents	O
+the	O
+results	O
+of	O
+treating	O
+IST	B-Disease
+by	O
+intratympanic	O
+instillation	O
+of	O
+lignocaine	B-Chemical
+(	O
+lidocaine	B-Chemical
+)	O
+2	O
+per	O
+cent	O
+through	O
+a	O
+grommet	O
+,	O
+for	O
+five	O
+weekly	O
+courses	O
+.	O
+
+Fifty	O
+-	O
+two	O
+patients	O
+suffering	O
+from	O
+intractable	O
+tinnitus	B-Disease
+entered	O
+this	O
+therapeutic	O
+trial	O
+,	O
+but	O
+only	O
+nine	O
+finished	O
+all	O
+five	O
+courses	O
+.	O
+
+In	O
+one	O
+patient	O
+,	O
+the	O
+tinnitus	B-Disease
+was	O
+almost	O
+completely	O
+abolished	O
+,	O
+but	O
+in	O
+all	O
+the	O
+nine	O
+patients	O
+the	O
+decompensated	O
+tinnitus	B-Disease
+changed	O
+to	O
+a	O
+compensated	O
+one	O
+.	O
+
+We	O
+suggest	O
+this	O
+mode	O
+of	O
+treatment	O
+for	O
+patients	O
+that	O
+were	O
+previously	O
+treated	O
+by	O
+drugs	O
+,	O
+acupuncture	O
+and	O
+biofeedback	O
+,	O
+with	O
+disappointing	O
+results	O
+.	O
+
+Patients	O
+should	O
+be	O
+warned	O
+about	O
+the	O
+side	O
+effects	O
+of	O
+vertigo	B-Disease
+and	O
+vomiting	B-Disease
+,	O
+which	O
+subsides	O
+gradually	O
+with	O
+every	O
+new	O
+instillation	O
+,	O
+and	O
+that	O
+the	O
+tinnitus	B-Disease
+may	O
+not	O
+disappear	O
+but	O
+will	O
+be	O
+alleviated	O
+,	O
+enabling	O
+them	O
+to	O
+cope	O
+more	O
+easily	O
+with	O
+the	O
+disease	O
+and	O
+lead	O
+a	O
+more	O
+normal	O
+life	O
+.	O
+
+The	O
+alpha3	O
+and	O
+beta4	O
+nicotinic	O
+acetylcholine	B-Chemical
+receptor	O
+subunits	O
+are	O
+necessary	O
+for	O
+nicotine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+and	O
+hypolocomotion	B-Disease
+in	O
+mice	O
+.	O
+
+Binding	O
+of	O
+nicotine	B-Chemical
+to	O
+nicotinic	O
+acetylcholine	B-Chemical
+receptors	O
+(	O
+nAChRs	O
+)	O
+elicits	O
+a	O
+series	O
+of	O
+dose	O
+-	O
+dependent	O
+behaviors	O
+that	O
+go	O
+from	O
+altered	O
+exploration	O
+,	O
+sedation	O
+,	O
+and	O
+tremors	B-Disease
+,	O
+to	O
+seizures	B-Disease
+and	O
+death	B-Disease
+.	O
+
+nAChRs	O
+are	O
+pentameric	O
+ion	O
+channels	O
+usually	O
+composed	O
+of	O
+alpha	O
+and	O
+beta	O
+subunits	O
+.	O
+
+A	O
+gene	O
+cluster	O
+comprises	O
+the	O
+alpha3	O
+,	O
+alpha5	O
+and	O
+beta4	O
+subunits	O
+,	O
+which	O
+coassemble	O
+to	O
+form	O
+functional	O
+receptors	O
+.	O
+
+We	O
+examined	O
+the	O
+role	O
+of	O
+the	O
+beta4	O
+subunits	O
+in	O
+nicotine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+and	O
+hypolocomotion	B-Disease
+in	O
+beta4	O
+homozygous	O
+null	O
+(	O
+beta4	O
+-	O
+/	O
+-	O
+)	O
+and	O
+alpha3	O
+heterozygous	O
+(	O
++	O
+/	O
+-	O
+)	O
+mice	O
+.	O
+
+beta4	O
+-	O
+/	O
+-	O
+mice	O
+were	O
+less	O
+sensitive	O
+to	O
+the	O
+effects	O
+of	O
+nicotine	B-Chemical
+both	O
+at	O
+low	O
+doses	O
+,	O
+measured	O
+as	O
+decreased	O
+exploration	O
+in	O
+an	O
+open	O
+field	O
+,	O
+and	O
+at	O
+high	O
+doses	O
+,	O
+measured	O
+as	O
+sensitivity	O
+to	O
+nicotine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+.	O
+
+Using	O
+in	O
+situ	O
+hybridization	O
+probes	O
+for	O
+the	O
+alpha3	O
+and	O
+alpha5	O
+subunits	O
+,	O
+we	O
+showed	O
+that	O
+alpha5	O
+mRNA	O
+levels	O
+are	O
+unchanged	O
+,	O
+whereas	O
+alpha3	O
+mRNA	O
+levels	O
+are	O
+selectively	O
+decreased	O
+in	O
+the	O
+mitral	O
+cell	O
+layer	O
+of	O
+the	O
+olfactory	O
+bulb	O
+,	O
+and	O
+the	O
+inferior	O
+and	O
+the	O
+superior	O
+colliculus	O
+of	O
+beta4	O
+-	O
+/	O
+-	O
+brains	O
+.	O
+
+alpha3	O
++	O
+/	O
+-	O
+mice	O
+were	O
+partially	O
+resistant	O
+to	O
+nicotine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+when	O
+compared	O
+to	O
+wild	O
+-	O
+type	O
+littermates	O
+.	O
+
+mRNA	O
+levels	O
+for	O
+the	O
+alpha5	O
+and	O
+the	O
+beta4	O
+subunits	O
+were	O
+unchanged	O
+in	O
+alpha3	O
++	O
+/	O
+-	O
+brains	O
+.	O
+
+Together	O
+,	O
+these	O
+results	O
+suggest	O
+that	O
+the	O
+beta4	O
+and	O
+the	O
+alpha3	O
+subunits	O
+are	O
+mediators	O
+of	O
+nicotine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+and	O
+hypolocomotion	B-Disease
+.	O
+
+The	O
+effects	O
+of	O
+sevoflurane	B-Chemical
+on	O
+lidocaine	B-Chemical
+-	O
+induced	O
+convulsions	B-Disease
+.	O
+
+The	O
+influence	O
+of	O
+sevoflurane	B-Chemical
+on	O
+lidocaine	B-Chemical
+-	O
+induced	O
+convulsions	B-Disease
+was	O
+studied	O
+in	O
+cats	O
+.	O
+
+The	O
+convulsive	B-Disease
+threshold	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+was	O
+41	O
+.	O
+4	O
++	O
+/	O
+-	O
+6	O
+.	O
+5	O
+mg	O
+.	O
+
+l	O
+(	O
+-	O
+1	O
+)	O
+with	O
+lidocaine	B-Chemical
+infusion	O
+(	O
+6	O
+mg	O
+.	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+.	O
+min	O
+(	O
+-	O
+1	O
+)	O
+)	O
+,	O
+increasing	O
+significantly	O
+to	O
+66	O
+.	O
+6	O
++	O
+/	O
+-	O
+10	O
+.	O
+9	O
+mg	O
+.	O
+
+l	O
+(	O
+-	O
+1	O
+)	O
+when	O
+the	O
+end	O
+-	O
+tidal	O
+concentration	O
+of	O
+sevoflurane	B-Chemical
+was	O
+0	O
+.	O
+8	O
+%	O
+.	O
+
+However	O
+,	O
+the	O
+threshold	O
+(	O
+61	O
+.	O
+6	O
++	O
+/	O
+-	O
+8	O
+.	O
+7	O
+mg	O
+.	O
+l	O
+(	O
+-	O
+1	O
+)	O
+)	O
+during	O
+1	O
+.	O
+6	O
+%	O
+sevoflurane	B-Chemical
+was	O
+not	O
+significant	O
+from	O
+that	O
+during	O
+0	O
+.	O
+8	O
+%	O
+sevoflurane	B-Chemical
+,	O
+indicating	O
+a	O
+celling	O
+effect	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
+difference	O
+in	O
+the	O
+convulsive	B-Disease
+threshold	O
+between	O
+sevoflurane	B-Chemical
+and	O
+enflurane	B-Chemical
+.	O
+
+The	O
+rise	O
+in	O
+blood	O
+pressure	O
+became	O
+less	O
+marked	O
+when	O
+higher	O
+concentrations	O
+of	O
+sevoflurane	B-Chemical
+or	O
+enflurane	B-Chemical
+were	O
+administered	O
+and	O
+the	O
+blood	O
+pressure	O
+at	O
+convulsions	B-Disease
+decreased	O
+significantly	O
+in	O
+1	O
+.	O
+6	O
+%	O
+sevoflurane	B-Chemical
+,	O
+and	O
+in	O
+0	O
+.	O
+8	O
+%	O
+and	O
+1	O
+.	O
+6	O
+%	O
+enflurane	B-Chemical
+.	O
+
+However	O
+,	O
+there	O
+was	O
+no	O
+significant	O
+difference	O
+in	O
+the	O
+lidocaine	B-Chemical
+concentrations	O
+measured	O
+when	O
+the	O
+systolic	O
+blood	O
+pressure	O
+became	O
+70	O
+mmHg	O
+.	O
+
+Apamin	B-Chemical
+,	O
+a	O
+selective	O
+blocker	O
+of	O
+calcium	B-Chemical
+-	O
+dependent	O
+potassium	B-Chemical
+channels	O
+,	O
+was	O
+administered	O
+intracerebroventricularly	O
+in	O
+rats	O
+anesthetized	O
+with	O
+0	O
+.	O
+8	O
+%	O
+sevoflurane	B-Chemical
+to	O
+investigate	O
+the	O
+mechanism	O
+of	O
+the	O
+anticonvulsive	O
+effects	O
+.	O
+
+Apamin	B-Chemical
+(	O
+10	O
+ng	O
+)	O
+had	O
+a	O
+tendency	O
+to	O
+decrease	O
+the	O
+convulsive	B-Disease
+threshold	O
+(	O
+21	O
+.	O
+6	O
++	O
+/	O
+-	O
+2	O
+.	O
+2	O
+to	O
+19	O
+.	O
+9	O
++	O
+/	O
+-	O
+2	O
+.	O
+5	O
+mg	O
+.	O
+l	O
+(	O
+-	O
+1	O
+)	O
+)	O
+but	O
+this	O
+was	O
+not	O
+statistically	O
+significant	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+sevoflurane	B-Chemical
+reduces	O
+the	O
+convulsive	B-Disease
+effect	O
+of	O
+lidocaine	B-Chemical
+toxicity	B-Disease
+but	O
+carries	O
+some	O
+risk	O
+due	O
+to	O
+circulatory	O
+depression	B-Disease
+.	O
+
+Cardiac	B-Disease
+toxicity	I-Disease
+observed	O
+in	O
+association	O
+with	O
+high	O
+-	O
+dose	O
+cyclophosphamide	B-Chemical
+-	O
+based	O
+chemotherapy	O
+for	O
+metastatic	O
+breast	B-Disease
+cancer	I-Disease
+.	O
+
+INTRODUCTION	O
+:	O
+Cyclophosphamide	B-Chemical
+is	O
+an	O
+alkylating	O
+agent	O
+given	O
+frequently	O
+as	O
+a	O
+component	O
+of	O
+many	O
+conditioning	O
+regimens	O
+.	O
+
+In	O
+high	O
+doses	O
+,	O
+its	O
+nonhematological	O
+dose	O
+-	O
+limiting	O
+toxicity	B-Disease
+is	O
+cardiomyopathy	B-Disease
+.	O
+
+STUDY	O
+DESIGN	O
+:	O
+We	O
+combined	O
+paclitaxel	B-Chemical
+,	O
+melphalan	B-Chemical
+and	O
+high	O
+-	O
+dose	O
+cyclophosphamide	B-Chemical
+,	O
+thiotepa	B-Chemical
+,	O
+and	O
+carboplatin	B-Chemical
+in	O
+a	O
+triple	O
+sequential	O
+high	O
+-	O
+dose	O
+regimen	O
+for	O
+patients	O
+with	O
+metastatic	O
+breast	B-Disease
+cancer	I-Disease
+.	O
+
+Analysis	O
+was	O
+performed	O
+on	O
+61	O
+women	O
+with	O
+chemotherapy	O
+-	O
+responsive	O
+metastatic	O
+breast	B-Disease
+cancer	I-Disease
+receiving	O
+96	O
+-	O
+h	O
+infusional	O
+cyclophosphamide	B-Chemical
+as	O
+part	O
+of	O
+a	O
+triple	O
+sequential	O
+high	O
+-	O
+dose	O
+regimen	O
+to	O
+assess	O
+association	O
+between	O
+presence	O
+of	O
+peritransplant	O
+congestive	B-Disease
+heart	I-Disease
+failure	I-Disease
+(	O
+CHF	B-Disease
+)	O
+and	O
+the	O
+following	O
+pretreatment	O
+characteristics	O
+:	O
+presence	O
+of	O
+electrocardiogram	O
+(	O
+EKG	O
+)	O
+abnormalities	O
+,	O
+age	O
+,	O
+hypertension	B-Disease
+,	O
+prior	O
+cardiac	O
+history	O
+,	O
+smoking	O
+,	O
+diabetes	B-Disease
+mellitus	I-Disease
+,	O
+prior	O
+use	O
+of	O
+anthracyclines	B-Chemical
+,	O
+and	O
+left	O
+-	O
+sided	O
+chest	O
+irradiation	O
+.	O
+
+RESULTS	O
+:	O
+Six	O
+of	O
+61	O
+women	O
+(	O
+10	O
+%	O
+)	O
+developed	O
+clinically	O
+reversible	O
+grade	O
+3	O
+CHF	B-Disease
+following	O
+infusional	O
+cyclophosphamide	B-Chemical
+with	O
+a	O
+median	O
+percent	O
+decline	O
+in	O
+ejection	O
+fraction	O
+of	O
+31	O
+%	O
+.	O
+
+Incidence	O
+of	O
+transient	O
+cyclophosphamide	B-Chemical
+-	O
+related	O
+cardiac	B-Disease
+toxicity	I-Disease
+(	O
+10	O
+%	O
+)	O
+is	O
+comparable	O
+to	O
+previous	O
+recorded	O
+literature	O
+.	O
+
+Older	O
+age	O
+was	O
+significantly	O
+correlated	O
+with	O
+the	O
+CHF	B-Disease
+development	O
+;	O
+with	O
+median	O
+ages	O
+for	O
+the	O
+entire	O
+group	O
+and	O
+for	O
+patients	O
+developing	O
+CHF	B-Disease
+of	O
+45	O
+and	O
+59	O
+,	O
+respectively	O
+.	O
+
+No	O
+association	O
+was	O
+found	O
+with	O
+other	O
+pretreatment	O
+characteristics	O
+.	O
+
+CONCLUSIONS	O
+:	O
+As	O
+a	O
+result	O
+of	O
+these	O
+findings	O
+,	O
+oncologists	O
+should	O
+carefully	O
+monitor	O
+fluid	O
+balance	O
+in	O
+older	O
+patients	O
+.	O
+
+Routine	O
+EKG	O
+monitoring	O
+during	O
+infusional	O
+cyclophosphamide	B-Chemical
+did	O
+not	O
+predict	O
+CHF	B-Disease
+development	O
+.	O
+
+Tremor	B-Disease
+side	O
+effects	O
+of	O
+salbutamol	B-Chemical
+,	O
+quantified	O
+by	O
+a	O
+laser	O
+pointer	O
+technique	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+study	O
+tremor	B-Disease
+side	O
+effects	O
+of	O
+salbutamol	B-Chemical
+an	O
+easily	O
+applicable	O
+,	O
+quick	O
+and	O
+low	O
+-	O
+priced	O
+method	O
+is	O
+needed	O
+.	O
+
+A	O
+new	O
+method	O
+using	O
+a	O
+commercially	O
+available	O
+,	O
+pen	O
+-	O
+shaped	O
+laser	O
+pointer	O
+was	O
+developed	O
+.	O
+
+Aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+determine	O
+sensitivity	O
+,	O
+reproducibility	O
+,	O
+reference	O
+values	O
+and	O
+the	O
+agreement	O
+with	O
+a	O
+questionnaire	O
+.	O
+
+METHODS	O
+:	O
+Tremor	B-Disease
+was	O
+measured	O
+using	O
+a	O
+laser	O
+pointer	O
+technique	O
+.	O
+
+To	O
+determine	O
+sensitivity	O
+we	O
+assessed	O
+tremor	B-Disease
+in	O
+44	O
+patients	O
+with	O
+obstructive	B-Disease
+lung	I-Disease
+disease	I-Disease
+after	O
+administration	O
+of	O
+cumulative	O
+doses	O
+of	O
+salbutamol	B-Chemical
+.	O
+
+Subjects	O
+were	O
+asked	O
+to	O
+aim	O
+at	O
+the	O
+centre	O
+of	O
+a	O
+target	O
+,	O
+subdivided	O
+in	O
+concentric	O
+circles	O
+,	O
+from	O
+5	O
+m	O
+distance	O
+.	O
+
+The	O
+circle	O
+in	O
+which	O
+the	O
+participant	O
+succeeded	O
+to	O
+aim	O
+was	O
+recorded	O
+in	O
+millimetres	O
+radius	O
+.	O
+
+In	O
+another	O
+series	O
+of	O
+measurements	O
+,	O
+reproducibility	O
+and	O
+reference	O
+values	O
+of	O
+the	O
+tremor	B-Disease
+was	O
+assessed	O
+in	O
+65	O
+healthy	O
+subjects	O
+in	O
+three	O
+sessions	O
+,	O
+at	O
+9	O
+a	O
+.	O
+m	O
+.	O
+,	O
+4	O
+p	O
+.	O
+m	O
+.	O
+and	O
+9	O
+a	O
+.	O
+m	O
+.	O
+,	O
+respectively	O
+,	O
+1	O
+week	O
+later	O
+.	O
+
+Postural	O
+tremor	B-Disease
+was	O
+measured	O
+with	O
+the	O
+arm	O
+horizontally	O
+outstretched	O
+rest	O
+tremor	B-Disease
+with	O
+the	O
+arm	O
+supported	O
+by	O
+an	O
+armrest	O
+and	O
+finally	O
+tremor	B-Disease
+was	O
+measured	O
+after	O
+holding	O
+a	O
+2	O
+-	O
+kg	O
+weight	O
+until	O
+exhaustion	O
+.	O
+
+Inter	O
+-	O
+observer	O
+variability	O
+was	O
+measured	O
+in	O
+a	O
+series	O
+of	O
+10	O
+healthy	O
+subjects	O
+.	O
+
+Tremor	B-Disease
+was	O
+measured	O
+simultaneously	O
+by	O
+two	O
+independent	O
+observers	O
+.	O
+
+RESULTS	O
+:	O
+Salbutamol	B-Chemical
+significantly	O
+increased	O
+tremor	B-Disease
+severity	O
+in	O
+patients	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+way	O
+.	O
+
+Within	O
+healthy	O
+adults	O
+no	O
+age	O
+-	O
+dependency	O
+could	O
+be	O
+found	O
+(	O
+b	O
+=	O
+0	O
+.	O
+262	O
+mm	O
+/	O
+year	O
+;	O
+P	O
+=	O
+0	O
+.	O
+72	O
+)	O
+.	O
+
+There	O
+was	O
+no	O
+agreement	O
+between	O
+the	O
+questionnaire	O
+and	O
+tremor	B-Disease
+severity	O
+(	O
+r	O
+=	O
+0	O
+.	O
+093	O
+;	O
+P	O
+=	O
+0	O
+.	O
+53	O
+)	O
+.	O
+
+Postural	O
+tremor	B-Disease
+showed	O
+no	O
+significant	O
+difference	O
+between	O
+the	O
+first	O
+and	O
+third	O
+session	O
+(	O
+P	O
+=	O
+0	O
+.	O
+07	O
+)	O
+.	O
+
+Support	O
+of	O
+the	O
+arm	O
+decreased	O
+tremor	B-Disease
+severity	O
+,	O
+exhaustion	O
+increased	O
+tremor	B-Disease
+severity	O
+significantly	O
+.	O
+
+A	O
+good	O
+agreement	O
+was	O
+found	O
+between	O
+two	O
+independent	O
+observers	O
+(	O
+interclass	O
+correlation	O
+coefficient	O
+0	O
+.	O
+72	O
+)	O
+.	O
+
+DISCUSSION	O
+:	O
+Quantifying	O
+tremor	B-Disease
+by	O
+using	O
+an	O
+inexpensive	O
+laser	O
+pointer	O
+is	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+children	O
+(	O
+<	O
+12	O
+years	O
+)	O
+a	O
+sensitive	O
+and	O
+reproducible	O
+method	O
+.	O
+
+Safety	O
+and	O
+adverse	O
+effects	O
+associated	O
+with	O
+raloxifene	B-Chemical
+:	O
+multiple	O
+outcomes	O
+of	O
+raloxifene	B-Chemical
+evaluation	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+examine	O
+the	O
+effect	O
+of	O
+raloxifene	B-Chemical
+on	O
+major	O
+adverse	O
+events	O
+that	O
+occur	O
+with	O
+postmenopausal	O
+estrogen	B-Chemical
+therapy	O
+or	O
+tamoxifen	B-Chemical
+.	O
+
+METHODS	O
+:	O
+The	O
+Multiple	O
+Outcomes	O
+of	O
+Raloxifene	B-Chemical
+Evaluation	O
+,	O
+a	O
+multicenter	O
+,	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+trial	O
+,	O
+enrolled	O
+7	O
+,	O
+705	O
+postmenopausal	O
+women	O
+with	O
+osteoporosis	B-Disease
+.	O
+
+Women	O
+were	O
+randomly	O
+assigned	O
+to	O
+raloxifene	B-Chemical
+60	O
+mg	O
+/	O
+d	O
+or	O
+120	O
+mg	O
+/	O
+d	O
+or	O
+placebo	O
+.	O
+
+Outcomes	O
+included	O
+venous	B-Disease
+thromboembolism	I-Disease
+,	O
+cataracts	B-Disease
+,	O
+gallbladder	B-Disease
+disease	I-Disease
+,	O
+and	O
+endometrial	B-Disease
+hyperplasia	I-Disease
+or	I-Disease
+cancer	I-Disease
+.	O
+
+RESULTS	O
+:	O
+During	O
+a	O
+mean	O
+follow	O
+-	O
+up	O
+of	O
+3	O
+.	O
+3	O
+years	O
+,	O
+raloxifene	B-Chemical
+was	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+for	O
+venous	B-Disease
+thromboembolism	I-Disease
+(	O
+relative	O
+risk	O
+[	O
+RR	O
+]	O
+2	O
+.	O
+1	O
+;	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+1	O
+.	O
+2	O
+-	O
+3	O
+.	O
+8	O
+)	O
+.	O
+
+The	O
+excess	O
+event	O
+rate	O
+was	O
+1	O
+.	O
+8	O
+per	O
+1	O
+,	O
+000	O
+woman	O
+-	O
+years	O
+(	O
+95	O
+%	O
+CI	O
+-	O
+0	O
+.	O
+5	O
+-	O
+4	O
+.	O
+1	O
+)	O
+,	O
+and	O
+the	O
+number	O
+needed	O
+to	O
+treat	O
+to	O
+cause	O
+1	O
+event	O
+was	O
+170	O
+(	O
+95	O
+%	O
+CI	O
+100	O
+-	O
+582	O
+)	O
+over	O
+3	O
+.	O
+3	O
+years	O
+.	O
+
+Risk	O
+in	O
+the	O
+raloxifene	B-Chemical
+group	O
+was	O
+higher	O
+than	O
+in	O
+the	O
+placebo	O
+group	O
+for	O
+the	O
+first	O
+2	O
+years	O
+,	O
+but	O
+decreased	O
+to	O
+about	O
+the	O
+same	O
+rate	O
+as	O
+in	O
+the	O
+placebo	O
+group	O
+thereafter	O
+.	O
+
+Raloxifene	B-Chemical
+did	O
+not	O
+increase	O
+risk	O
+for	O
+cataracts	B-Disease
+(	O
+RR	O
+0	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+8	O
+-	O
+1	O
+.	O
+1	O
+)	O
+,	O
+gallbladder	B-Disease
+disease	I-Disease
+(	O
+RR	O
+1	O
+.	O
+0	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+7	O
+-	O
+1	O
+.	O
+3	O
+)	O
+,	O
+endometrial	B-Disease
+hyperplasia	I-Disease
+(	O
+RR	O
+1	O
+.	O
+3	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+4	O
+-	O
+5	O
+.	O
+1	O
+)	O
+,	O
+or	O
+endometrial	B-Disease
+cancer	I-Disease
+(	O
+RR	O
+0	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+3	O
+-	O
+2	O
+.	O
+7	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+Raloxifene	B-Chemical
+was	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+for	O
+venous	B-Disease
+thromboembolism	I-Disease
+,	O
+but	O
+there	O
+was	O
+no	O
+increased	O
+risk	O
+for	O
+cataracts	B-Disease
+,	O
+gallbladder	B-Disease
+disease	I-Disease
+,	O
+endometrial	B-Disease
+hyperplasia	I-Disease
+,	O
+or	O
+endometrial	B-Disease
+cancer	I-Disease
+.	O
+
+LEVEL	O
+OF	O
+EVIDENCE	O
+:	O
+I	O
+
+Optimization	O
+of	O
+levodopa	B-Chemical
+therapy	O
+.	O
+
+While	O
+there	O
+is	O
+no	O
+single	O
+correct	O
+starting	O
+dose	O
+for	O
+levodopa	B-Chemical
+therapy	O
+,	O
+many	O
+individuals	O
+can	O
+be	O
+started	O
+on	O
+either	O
+the	O
+25	O
+/	O
+100	O
+or	O
+controlled	O
+-	O
+release	O
+formula	O
+,	O
+following	O
+the	O
+general	O
+rule	O
+not	O
+to	O
+attempt	O
+to	O
+titrate	O
+carbidopa	B-Chemical
+-	O
+levodopa	B-Chemical
+to	O
+the	O
+point	O
+of	O
+"	O
+normality	O
+,	O
+"	O
+which	O
+can	O
+lead	O
+to	O
+toxicity	B-Disease
+.	O
+
+The	O
+physician	O
+should	O
+also	O
+determine	O
+the	O
+proper	O
+use	O
+of	O
+any	O
+adjunctive	O
+medications	O
+;	O
+such	O
+combined	O
+therapy	O
+has	O
+become	O
+the	O
+standard	O
+approach	O
+to	O
+treatment	O
+.	O
+
+Following	O
+the	O
+initial	O
+period	O
+of	O
+therapy	O
+,	O
+emerging	O
+difficulties	O
+require	O
+a	O
+reassessment	O
+of	O
+therapeutic	O
+approaches	O
+,	O
+such	O
+as	O
+dosage	O
+adjustment	O
+or	O
+introduction	O
+of	O
+a	O
+dopamine	B-Chemical
+agonist	O
+.	O
+
+Other	O
+possible	O
+adverse	O
+effects	O
+-	O
+-	O
+such	O
+as	O
+gastrointestinal	B-Disease
+disorders	I-Disease
+,	O
+orthostatic	B-Disease
+hypotension	I-Disease
+,	O
+levodopa	B-Chemical
+-	O
+induced	O
+psychosis	B-Disease
+,	O
+sleep	B-Disease
+disturbances	I-Disease
+or	O
+parasomnias	B-Disease
+,	O
+or	O
+drug	O
+interactions	O
+-	O
+-	O
+also	O
+require	O
+carefully	O
+monitored	O
+individual	O
+treatment	O
+.	O
+
+Nonpharmacologic	O
+concerns	O
+can	O
+help	O
+the	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+patient	O
+achieve	O
+and	O
+maintain	O
+optimal	O
+functioning	O
+,	O
+including	O
+daily	O
+exercise	O
+,	O
+physical	O
+therapy	O
+,	O
+and	O
+involvement	O
+with	O
+support	O
+groups	O
+.	O
+
+Long	O
+term	O
+audiological	O
+evaluation	O
+of	O
+beta	B-Disease
+-	I-Disease
+thalassemic	I-Disease
+patients	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+identify	O
+the	O
+incidence	O
+and	O
+to	O
+monitor	O
+the	O
+progression	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+in	O
+children	O
+and	O
+young	O
+adults	O
+with	O
+beta	B-Disease
+-	I-Disease
+thalassemia	I-Disease
+major	O
+.	O
+
+METHODS	O
+:	O
+One	O
+hundred	O
+and	O
+four	O
+(	O
+104	O
+)	O
+patients	O
+aged	O
+6	O
+-	O
+35	O
+years	O
+(	O
+mean	O
+17	O
+,	O
+2	O
+years	O
+)	O
+participated	O
+in	O
+the	O
+study	O
+.	O
+
+All	O
+patients	O
+were	O
+on	O
+a	O
+regular	O
+transfusion	O
+-	O
+chelation	O
+program	O
+maintaining	O
+a	O
+mean	O
+hemoglobin	O
+level	O
+of	O
+9	O
+.	O
+5	O
+gr	O
+/	O
+dl	O
+.	O
+
+Subjects	O
+were	O
+receiving	O
+desferrioxamine	B-Chemical
+(	O
+DFO	B-Chemical
+)	O
+chelation	O
+treatment	O
+with	O
+a	O
+mean	O
+daily	O
+dose	O
+of	O
+50	O
+-	O
+60	O
+mg	O
+/	O
+kg	O
+,	O
+5	O
+-	O
+6	O
+days	O
+a	O
+week	O
+during	O
+the	O
+first	O
+six	O
+years	O
+of	O
+the	O
+study	O
+,	O
+which	O
+was	O
+then	O
+reduced	O
+to	O
+40	O
+-	O
+50	O
+mg	O
+/	O
+kg	O
+for	O
+the	O
+following	O
+eight	O
+years	O
+.	O
+
+Patients	O
+were	O
+followed	O
+for	O
+8	O
+-	O
+14	O
+years	O
+.	O
+
+RESULTS	O
+:	O
+Overall	O
+,	O
+21	O
+out	O
+of	O
+104	O
+patients	O
+(	O
+20	O
+.	O
+2	O
+%	O
+)	O
+presented	O
+with	O
+high	O
+frequency	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+(	O
+SNHL	B-Disease
+)	O
+,	O
+either	O
+unilateral	O
+or	O
+bilateral	O
+.	O
+
+No	O
+ototoxic	B-Disease
+factor	O
+,	O
+other	O
+than	O
+DFO	B-Chemical
+,	O
+was	O
+present	O
+in	O
+any	O
+of	O
+the	O
+patients	O
+.	O
+
+Patients	O
+with	O
+SNHL	B-Disease
+presented	O
+with	O
+relatively	O
+lower	O
+serum	O
+ferritin	O
+levels	O
+than	O
+those	O
+with	O
+normal	O
+hearing	O
+,	O
+however	O
+,	O
+no	O
+statistically	O
+significant	O
+difference	O
+was	O
+observed	O
+.	O
+
+Subjects	O
+with	O
+SNHL	B-Disease
+were	O
+submitted	O
+to	O
+DFO	B-Chemical
+reduction	O
+or	O
+temporary	O
+withdrawal	O
+.	O
+
+Following	O
+intervention	O
+,	O
+7	O
+out	O
+of	O
+21	O
+affected	O
+patients	O
+recovered	O
+,	O
+10	O
+remained	O
+stable	O
+and	O
+4	O
+demonstrated	O
+aggravation	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+findings	O
+are	O
+indicative	O
+of	O
+DFO	B-Chemical
+'	O
+s	O
+contributing	O
+role	O
+in	O
+the	O
+development	O
+of	O
+hearing	B-Disease
+impairment	I-Disease
+.	O
+
+Regular	O
+audiologic	O
+evaluation	O
+is	O
+imperative	O
+in	O
+all	O
+thalassemic	B-Disease
+patients	O
+so	O
+that	O
+early	O
+changes	O
+may	O
+be	O
+recognized	O
+and	O
+treatment	O
+may	O
+be	O
+judiciously	O
+adjusted	O
+in	O
+order	O
+to	O
+prevent	O
+or	O
+reverse	O
+hearing	B-Disease
+impairment	I-Disease
+.	O
+
+Individual	O
+differences	O
+in	O
+renal	O
+ACE	O
+activity	O
+in	O
+healthy	O
+rats	O
+predict	O
+susceptibility	O
+to	O
+adriamycin	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+damage	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+In	O
+man	O
+,	O
+differences	O
+in	O
+angiotensin	B-Chemical
+-	O
+converting	O
+enzyme	O
+(	O
+ACE	O
+)	O
+levels	O
+,	O
+related	O
+to	O
+ACE	O
+(	O
+I	O
+/	O
+D	O
+)	O
+genotype	O
+,	O
+are	O
+associated	O
+with	O
+renal	O
+prognosis	O
+.	O
+
+This	O
+raises	O
+the	O
+hypothesis	O
+that	O
+individual	O
+differences	O
+in	O
+renal	O
+ACE	O
+activity	O
+are	O
+involved	O
+in	O
+renal	O
+susceptibility	O
+to	O
+inflicted	O
+damage	O
+.	O
+
+Therefore	O
+,	O
+we	O
+studied	O
+the	O
+predictive	O
+effect	O
+of	O
+renal	O
+ACE	O
+activity	O
+for	O
+the	O
+severity	O
+of	O
+renal	B-Disease
+damage	I-Disease
+induced	O
+by	O
+a	O
+single	O
+injection	O
+of	O
+adriamycin	B-Chemical
+in	O
+rats	O
+.	O
+
+METHODS	O
+:	O
+Renal	O
+ACE	O
+activity	O
+(	O
+Hip	B-Chemical
+-	I-Chemical
+His	I-Chemical
+-	I-Chemical
+Leu	I-Chemical
+cleavage	O
+by	O
+cortical	O
+homogenates	O
+)	O
+was	O
+determined	O
+by	O
+renal	O
+biopsy	O
+in	O
+27	O
+adult	O
+male	O
+Wistar	O
+rats	O
+.	O
+
+After	O
+1	O
+week	O
+of	O
+recovery	O
+,	O
+proteinuria	B-Disease
+was	O
+induced	O
+by	O
+adriamycin	B-Chemical
+[	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+intravenously	O
+(	O
+i	O
+.	O
+v	O
+.	O
+)	O
+n	O
+=	O
+18	O
+;	O
+controls	O
+,	O
+saline	O
+i	O
+.	O
+v	O
+.	O
+n	O
+=	O
+9	O
+]	O
+.	O
+
+Proteinuria	B-Disease
+was	O
+measured	O
+every	O
+2	O
+weeks	O
+.	O
+
+After	O
+12	O
+weeks	O
+,	O
+rats	O
+were	O
+sacrificed	O
+and	O
+their	O
+kidneys	O
+harvested	O
+.	O
+
+RESULTS	O
+:	O
+As	O
+anticipated	O
+,	O
+adriamycin	B-Chemical
+elicited	O
+nephrotic	B-Disease
+range	O
+proteinuria	B-Disease
+,	O
+renal	B-Disease
+interstitial	I-Disease
+damage	I-Disease
+and	O
+mild	O
+focal	B-Disease
+glomerulosclerosis	I-Disease
+.	O
+
+Baseline	O
+renal	O
+ACE	O
+positively	O
+correlated	O
+with	O
+the	O
+relative	O
+rise	O
+in	O
+proteinuria	B-Disease
+after	O
+adriamycin	B-Chemical
+(	O
+r	O
+=	O
+0	O
+.	O
+62	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+renal	O
+interstitial	O
+alpha	O
+-	O
+smooth	O
+muscle	O
+actin	O
+(	O
+r	O
+=	O
+0	O
+.	O
+49	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+interstitial	O
+macrophage	O
+influx	O
+(	O
+r	O
+=	O
+0	O
+.	O
+56	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+interstitial	O
+collagen	O
+III	O
+(	O
+r	O
+=	O
+0	O
+.	O
+53	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+,	O
+glomerular	O
+alpha	O
+-	O
+smooth	O
+muscle	O
+actin	O
+(	O
+r	O
+=	O
+0	O
+.	O
+74	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+and	O
+glomerular	O
+desmin	O
+(	O
+r	O
+=	O
+0	O
+.	O
+48	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Baseline	O
+renal	O
+ACE	O
+did	O
+not	O
+correlate	O
+with	O
+focal	B-Disease
+glomerulosclerosis	I-Disease
+(	O
+r	O
+=	O
+0	O
+.	O
+22	O
+,	O
+NS	O
+)	O
+.	O
+
+In	O
+controls	O
+,	O
+no	O
+predictive	O
+values	O
+for	O
+renal	O
+parameters	O
+were	O
+observed	O
+.	O
+
+CONCLUSION	O
+:	O
+Individual	O
+differences	O
+in	O
+renal	O
+ACE	O
+activity	O
+predict	O
+the	O
+severity	O
+of	O
+adriamycin	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+damage	I-Disease
+in	O
+this	O
+outbred	O
+rat	O
+strain	O
+.	O
+
+This	O
+supports	O
+the	O
+assumption	O
+that	O
+differences	O
+in	O
+renal	O
+ACE	O
+activity	O
+predispose	O
+to	O
+a	O
+less	O
+favourable	O
+course	O
+of	O
+renal	B-Disease
+damage	I-Disease
+.	O
+
+Recurrent	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+induced	O
+by	O
+azithromycin	B-Chemical
+.	O
+
+A	O
+14	O
+-	O
+year	O
+-	O
+old	O
+girl	O
+is	O
+reported	O
+with	O
+recurrent	O
+,	O
+azithromycin	B-Chemical
+-	O
+induced	O
+,	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+.	O
+
+The	O
+second	O
+episode	O
+was	O
+more	O
+severe	O
+than	O
+the	O
+first	O
+;	O
+and	O
+although	O
+both	O
+were	O
+treated	O
+with	O
+intensive	O
+corticosteroid	O
+therapy	O
+,	O
+renal	O
+function	O
+remained	O
+impaired	O
+.	O
+
+Although	O
+most	O
+cases	O
+of	O
+antibiotic	O
+induced	O
+acute	O
+interstitial	B-Disease
+nephritis	I-Disease
+are	O
+benign	O
+and	O
+self	O
+-	O
+limited	O
+,	O
+some	O
+patients	O
+are	O
+at	O
+risk	O
+for	O
+permanent	O
+renal	B-Disease
+injury	I-Disease
+.	O
+
+Spironolactone	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+insufficiency	I-Disease
+and	O
+hyperkalemia	B-Disease
+in	O
+patients	O
+with	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+A	O
+previous	O
+randomized	O
+controlled	O
+trial	O
+evaluating	O
+the	O
+use	O
+of	O
+spironolactone	B-Chemical
+in	O
+heart	B-Disease
+failure	I-Disease
+patients	O
+reported	O
+a	O
+low	O
+risk	O
+of	O
+hyperkalemia	B-Disease
+(	O
+2	O
+%	O
+)	O
+and	O
+renal	B-Disease
+insufficiency	I-Disease
+(	O
+0	O
+%	O
+)	O
+.	O
+
+Because	O
+treatments	O
+for	O
+heart	B-Disease
+failure	I-Disease
+have	O
+changed	O
+since	O
+the	O
+benefits	O
+of	O
+spironolactone	B-Chemical
+were	O
+reported	O
+,	O
+the	O
+prevalence	O
+of	O
+these	O
+complications	O
+may	O
+differ	O
+in	O
+current	O
+clinical	O
+practice	O
+.	O
+
+We	O
+therefore	O
+sought	O
+to	O
+determine	O
+the	O
+prevalence	O
+and	O
+clinical	O
+associations	O
+of	O
+hyperkalemia	B-Disease
+and	O
+renal	B-Disease
+insufficiency	I-Disease
+in	O
+heart	B-Disease
+failure	I-Disease
+patients	O
+treated	O
+with	O
+spironolactone	B-Chemical
+.	O
+
+METHODS	O
+:	O
+We	O
+performed	O
+a	O
+case	O
+control	O
+study	O
+of	O
+heart	B-Disease
+failure	I-Disease
+patients	O
+treated	O
+with	O
+spironolactone	B-Chemical
+in	O
+our	O
+clinical	O
+practice	O
+.	O
+
+Cases	O
+were	O
+patients	O
+who	O
+developed	O
+hyperkalemia	B-Disease
+(	O
+K	B-Chemical
+(	O
++	O
+)	O
+>	O
+5	O
+.	O
+0	O
+mEq	O
+/	O
+L	O
+)	O
+or	O
+renal	B-Disease
+insufficiency	I-Disease
+(	O
+Cr	B-Chemical
+>	O
+or	O
+=	O
+2	O
+.	O
+5	O
+mg	O
+/	O
+dL	O
+)	O
+,	O
+and	O
+they	O
+were	O
+compared	O
+to	O
+2	O
+randomly	O
+selected	O
+controls	O
+per	O
+case	O
+.	O
+
+Clinical	O
+characteristics	O
+,	O
+medications	O
+,	O
+and	O
+serum	O
+chemistries	O
+at	O
+baseline	O
+and	O
+follow	O
+-	O
+up	O
+time	O
+periods	O
+were	O
+compared	O
+.	O
+
+RESULTS	O
+:	O
+Sixty	O
+-	O
+seven	O
+of	O
+926	O
+patients	O
+(	O
+7	O
+.	O
+2	O
+%	O
+)	O
+required	O
+discontinuation	O
+of	O
+spironolactone	B-Chemical
+due	O
+to	O
+hyperkalemia	B-Disease
+(	O
+n	O
+=	O
+33	O
+)	O
+or	O
+renal	B-Disease
+failure	I-Disease
+(	O
+n	O
+=	O
+34	O
+)	O
+.	O
+
+Patients	O
+who	O
+developed	O
+hyperkalemia	B-Disease
+were	O
+older	O
+and	O
+more	O
+likely	O
+to	O
+have	O
+diabetes	B-Disease
+,	O
+had	O
+higher	O
+baseline	O
+serum	O
+potassium	B-Chemical
+levels	O
+and	O
+lower	O
+baseline	O
+potassium	B-Chemical
+supplement	O
+doses	O
+,	O
+and	O
+were	O
+more	O
+likely	O
+to	O
+be	O
+treated	O
+with	O
+beta	O
+-	O
+blockers	O
+than	O
+controls	O
+(	O
+n	O
+=	O
+134	O
+)	O
+.	O
+
+Patients	O
+who	O
+developed	O
+renal	B-Disease
+insufficiency	I-Disease
+had	O
+lower	O
+baseline	O
+body	O
+weight	O
+and	O
+higher	O
+baseline	O
+serum	O
+creatinine	B-Chemical
+,	O
+required	O
+higher	O
+doses	O
+of	O
+loop	O
+diuretics	O
+,	O
+and	O
+were	O
+more	O
+likely	O
+to	O
+be	O
+treated	O
+with	O
+thiazide	B-Chemical
+diuretics	O
+than	O
+controls	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Spironolactone	B-Chemical
+-	O
+induced	O
+hyperkalemia	B-Disease
+and	O
+renal	B-Disease
+insufficiency	I-Disease
+are	O
+more	O
+common	O
+in	O
+our	O
+clinical	O
+experience	O
+than	O
+reported	O
+previously	O
+.	O
+
+This	O
+difference	O
+is	O
+explained	O
+by	O
+patient	O
+comorbidities	O
+and	O
+more	O
+frequent	O
+use	O
+of	O
+beta	O
+-	O
+blockers	O
+.	O
+
+Acute	O
+reserpine	B-Chemical
+and	O
+subchronic	O
+haloperidol	B-Chemical
+treatments	O
+change	O
+synaptosomal	O
+brain	O
+glutamate	B-Chemical
+uptake	O
+and	O
+elicit	O
+orofacial	B-Disease
+dyskinesia	I-Disease
+in	O
+rats	O
+.	O
+
+Reserpine	B-Chemical
+-	O
+and	O
+haloperidol	B-Chemical
+-	O
+induced	O
+orofacial	B-Disease
+dyskinesia	I-Disease
+are	O
+putative	O
+animal	O
+models	O
+of	O
+tardive	B-Disease
+dyskinesia	I-Disease
+(	O
+TD	B-Disease
+)	O
+whose	O
+pathophysiology	O
+has	O
+been	O
+related	O
+to	O
+free	O
+radical	O
+generation	O
+and	O
+oxidative	O
+stress	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+the	O
+authors	O
+induced	O
+orofacial	B-Disease
+dyskinesia	I-Disease
+by	O
+acute	O
+reserpine	B-Chemical
+and	O
+subchronic	O
+haloperidol	B-Chemical
+administration	O
+to	O
+rats	O
+.	O
+
+Reserpine	B-Chemical
+injection	O
+(	O
+one	O
+dose	O
+of	O
+1	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+)	O
+every	O
+other	O
+day	O
+for	O
+3	O
+days	O
+caused	O
+a	O
+significant	O
+increase	O
+in	O
+vacuous	O
+chewing	O
+,	O
+tongue	O
+protrusion	O
+and	O
+duration	O
+of	O
+facial	O
+twitching	O
+,	O
+compared	O
+to	O
+the	O
+control	O
+.	O
+
+Haloperidol	B-Chemical
+administration	O
+(	O
+one	O
+dose	O
+of	O
+12	O
+mg	O
+/	O
+kg	O
+once	O
+a	O
+week	O
+s	O
+.	O
+c	O
+.	O
+)	O
+for	O
+4	O
+weeks	O
+caused	O
+an	O
+increase	O
+in	O
+vacuous	O
+chewing	O
+,	O
+tongue	O
+protrusion	O
+and	O
+duration	O
+of	O
+facial	O
+twitching	O
+observed	O
+in	O
+four	O
+weekly	O
+evaluations	O
+.	O
+
+After	O
+the	O
+treatments	O
+and	O
+behavioral	O
+observation	O
+,	O
+glutamate	B-Chemical
+uptake	O
+by	O
+segments	O
+of	O
+the	O
+brain	O
+was	O
+analyzed	O
+.	O
+
+A	O
+decreased	O
+glutamate	B-Chemical
+uptake	O
+was	O
+observed	O
+in	O
+the	O
+subcortical	O
+parts	O
+of	O
+animals	O
+treated	O
+with	O
+reserpine	B-Chemical
+and	O
+haloperidol	B-Chemical
+,	O
+compared	O
+to	O
+the	O
+control	O
+.	O
+
+Importantly	O
+,	O
+a	O
+decrease	O
+in	O
+glutamate	B-Chemical
+uptake	O
+correlates	O
+negatively	O
+with	O
+an	O
+increase	O
+in	O
+the	O
+incidence	O
+of	O
+orofacial	B-Disease
+diskinesia	I-Disease
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+early	O
+changes	O
+in	O
+glutamate	B-Chemical
+transport	O
+may	O
+be	O
+related	O
+to	O
+the	O
+development	O
+of	O
+vacuous	O
+chewing	O
+movements	O
+in	O
+rats	O
+.	O
+
+Ceftriaxone	B-Chemical
+-	O
+associated	O
+biliary	B-Disease
+pseudolithiasis	I-Disease
+in	O
+paediatric	O
+surgical	O
+patients	O
+.	O
+
+It	O
+is	O
+well	O
+known	O
+that	O
+ceftriaxone	B-Chemical
+leads	O
+to	O
+pseudolithiasis	B-Disease
+in	O
+some	O
+patients	O
+.	O
+
+Clinical	O
+and	O
+experimental	O
+studies	O
+also	O
+suggest	O
+that	O
+situations	O
+causing	O
+gallbladder	B-Disease
+dysfunction	I-Disease
+,	O
+such	O
+as	O
+fasting	O
+,	O
+may	O
+have	O
+a	O
+role	O
+for	O
+the	O
+development	O
+of	O
+pseudolithiasis	B-Disease
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+prospectively	O
+evaluated	O
+the	O
+incidence	O
+and	O
+clinical	O
+importance	O
+of	O
+pseudolithiasis	B-Disease
+in	O
+paediatric	O
+surgical	O
+patients	O
+receiving	O
+ceftriaxone	B-Chemical
+treatment	O
+,	O
+who	O
+often	O
+had	O
+to	O
+fast	O
+in	O
+the	O
+post	O
+-	O
+operative	O
+period	O
+.	O
+
+Fifty	O
+children	O
+who	O
+were	O
+given	O
+ceftriaxone	B-Chemical
+were	O
+evaluated	O
+by	O
+serial	O
+abdominal	O
+sonograms	O
+.	O
+
+Of	O
+those	O
+,	O
+13	O
+(	O
+26	O
+%	O
+)	O
+developed	O
+biliary	O
+pathology	O
+.	O
+
+Comparison	O
+of	O
+the	O
+patients	O
+with	O
+or	O
+without	O
+pseudolithiasis	B-Disease
+revealed	O
+no	O
+significant	O
+difference	O
+with	O
+respect	O
+to	O
+age	O
+,	O
+sex	O
+,	O
+duration	O
+of	O
+the	O
+treatment	O
+and	O
+starvation	O
+variables	O
+.	O
+
+After	O
+cessation	O
+of	O
+the	O
+treatment	O
+,	O
+pseudolithiasis	B-Disease
+resolved	O
+spontaneously	O
+within	O
+a	O
+short	O
+period	O
+.	O
+
+The	O
+incidence	O
+of	O
+pseudolithiasis	B-Disease
+is	O
+not	O
+affected	O
+by	O
+fasting	O
+.	O
+
+Coronary	B-Disease
+aneurysm	I-Disease
+after	O
+implantation	O
+of	O
+a	O
+paclitaxel	B-Chemical
+-	O
+eluting	O
+stent	O
+.	O
+
+Formation	O
+of	O
+coronary	B-Disease
+aneurysm	I-Disease
+is	O
+a	O
+rare	O
+complication	O
+of	O
+stenting	O
+with	O
+bare	O
+metal	O
+stents	O
+,	O
+but	O
+based	O
+on	O
+experimental	O
+studies	O
+drug	O
+-	O
+eluting	O
+stents	O
+may	O
+induce	O
+toxic	O
+effects	O
+on	O
+the	O
+vessel	O
+wall	O
+with	O
+incomplete	O
+stent	O
+apposition	O
+,	O
+aneurysm	B-Disease
+formation	O
+and	O
+with	O
+the	O
+potential	O
+of	O
+stent	O
+thrombosis	B-Disease
+or	O
+vessel	B-Disease
+rupture	I-Disease
+.	O
+
+We	O
+present	O
+a	O
+43	O
+-	O
+year	O
+-	O
+old	O
+man	O
+who	O
+developed	O
+a	O
+coronary	B-Disease
+aneurysm	I-Disease
+in	O
+the	O
+right	O
+coronary	O
+artery	O
+6	O
+months	O
+after	O
+receiving	O
+a	O
+paclitaxel	B-Chemical
+-	O
+eluting	O
+stent	O
+.	O
+
+The	O
+patient	O
+was	O
+asymptomatic	O
+and	O
+the	O
+aneurysm	B-Disease
+was	O
+detected	O
+in	O
+a	O
+routine	O
+control	O
+.	O
+
+Angiography	O
+and	O
+intracoronary	O
+ultrasound	O
+demonstrated	O
+lack	O
+of	O
+contact	O
+between	O
+stent	O
+and	O
+vessel	O
+wall	O
+in	O
+a	O
+15	O
+-	O
+mm	O
+long	O
+segment	O
+with	O
+maximal	O
+aneurysm	B-Disease
+diameter	O
+of	O
+6	O
+.	O
+0	O
+mm	O
+.	O
+
+The	O
+patient	O
+was	O
+successfully	O
+treated	O
+with	O
+a	O
+graft	O
+stent	O
+.	O
+
+Causes	O
+of	O
+acute	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+in	O
+patients	O
+receiving	O
+kidney	O
+transplantation	O
+.	O
+
+OBJECTIVES	O
+:	O
+Thrombotic	B-Disease
+microangiopathy	I-Disease
+is	O
+a	O
+well	O
+-	O
+known	O
+problem	O
+in	O
+patients	O
+following	O
+renal	O
+transplantation	O
+.	O
+
+In	O
+postrenal	O
+transplantation	O
+,	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+is	O
+often	O
+a	O
+reflection	O
+of	O
+hemolytic	B-Disease
+uremic	I-Disease
+syndrome	I-Disease
+.	O
+
+We	O
+aimed	O
+to	O
+determine	O
+the	O
+causes	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+in	O
+a	O
+population	O
+of	O
+renal	O
+transplantation	O
+recipients	O
+and	O
+discuss	O
+the	O
+literature	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+:	O
+We	O
+investigated	O
+the	O
+causes	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+during	O
+a	O
+1	O
+-	O
+year	O
+period	O
+,	O
+from	O
+June	O
+2003	O
+to	O
+June	O
+2004	O
+,	O
+at	O
+the	O
+King	O
+Fahad	O
+National	O
+Guard	O
+Hospital	O
+in	O
+Riyadh	O
+,	O
+Saudi	O
+Arabia	O
+,	O
+by	O
+reviewing	O
+the	O
+slides	O
+of	O
+all	O
+transplant	O
+biopsies	O
+(	O
+n	O
+=	O
+25	O
+)	O
+performed	O
+during	O
+this	O
+interval	O
+.	O
+
+Pre	O
+-	O
+and	O
+posttransplant	O
+crossmatching	O
+was	O
+done	O
+when	O
+possible	O
+.	O
+
+RESULTS	O
+:	O
+Five	O
+cases	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+were	O
+found	O
+.	O
+
+Three	O
+of	O
+these	O
+cases	O
+were	O
+from	O
+the	O
+25	O
+transplantations	O
+performed	O
+at	O
+King	O
+Fahad	O
+National	O
+Guard	O
+Hospital	O
+,	O
+while	O
+the	O
+other	O
+2	O
+transplantations	O
+had	O
+been	O
+performed	O
+abroad	O
+and	O
+were	O
+referred	O
+to	O
+us	O
+for	O
+follow	O
+-	O
+up	O
+.	O
+
+Three	O
+cases	O
+were	O
+related	O
+to	O
+cyclosporine	B-Chemical
+,	O
+and	O
+1	O
+case	O
+was	O
+secondary	O
+to	O
+both	O
+cyclosporine	B-Chemical
+and	O
+tacrolimus	B-Chemical
+.	O
+
+The	O
+fifth	O
+case	O
+had	O
+features	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+related	O
+to	O
+an	O
+antiphospholipid	B-Disease
+syndrome	I-Disease
+in	O
+a	O
+patient	O
+with	O
+systemic	B-Disease
+lupus	I-Disease
+erythematosus	I-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+In	O
+the	O
+literature	O
+,	O
+the	O
+most	O
+-	O
+frequent	O
+cause	O
+of	O
+hemolytic	B-Disease
+uremic	I-Disease
+syndrome	I-Disease
+in	O
+patients	O
+following	O
+renal	O
+transplantation	O
+is	O
+recurrence	O
+of	O
+the	O
+hemolytic	B-Disease
+uremic	I-Disease
+syndrome	I-Disease
+.	O
+
+Other	O
+causes	O
+include	O
+drug	O
+-	O
+related	O
+(	O
+cyclosporine	B-Chemical
+,	O
+tacrolimus	B-Chemical
+)	O
+toxicity	B-Disease
+,	O
+procoagulant	O
+status	O
+,	O
+and	O
+antibody	O
+-	O
+mediated	O
+rejection	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+most	O
+-	O
+frequent	O
+cause	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+was	O
+drug	O
+related	O
+,	O
+secondary	O
+mainly	O
+to	O
+cyclosporine	B-Chemical
+.	O
+
+In	O
+the	O
+current	O
+study	O
+,	O
+the	O
+frequency	O
+of	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+was	O
+similar	O
+to	O
+the	O
+percentage	O
+reported	O
+in	O
+the	O
+literature	O
+(	O
+20	O
+%	O
+)	O
+.	O
+
+Comparison	O
+of	O
+developmental	O
+toxicity	B-Disease
+of	O
+selective	O
+and	O
+non	O
+-	O
+selective	O
+cyclooxygenase	O
+-	O
+2	O
+inhibitors	O
+in	O
+CRL	O
+:	O
+(	O
+WI	O
+)	O
+WUBR	O
+Wistar	O
+rats	O
+-	O
+-	O
+DFU	B-Chemical
+and	O
+piroxicam	B-Chemical
+study	O
+.	O
+
+BACKGROUND	O
+:	O
+Cyclooxygenase	O
+(	O
+COX	O
+)	O
+inhibitors	O
+are	O
+one	O
+of	O
+the	O
+most	O
+often	O
+ingested	O
+drugs	O
+during	O
+pregnancy	O
+.	O
+
+Unlike	O
+general	O
+toxicity	B-Disease
+data	O
+,	O
+their	O
+prenatal	O
+toxic	O
+effects	O
+were	O
+not	O
+extensively	O
+studied	O
+before	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+experiment	O
+was	O
+to	O
+evaluate	O
+the	O
+developmental	O
+toxicity	B-Disease
+of	O
+the	O
+non	O
+-	O
+selective	O
+(	O
+piroxicam	B-Chemical
+)	O
+and	O
+selective	O
+(	O
+DFU	B-Chemical
+;	O
+5	B-Chemical
+,	I-Chemical
+5	I-Chemical
+-	I-Chemical
+dimethyl	I-Chemical
+-	I-Chemical
+3	I-Chemical
+-	I-Chemical
+(	I-Chemical
+3	I-Chemical
+-	I-Chemical
+fluorophenyl	I-Chemical
+)	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+4	I-Chemical
+-	I-Chemical
+methylsulphonyl	I-Chemical
+)	I-Chemical
+phenyl	I-Chemical
+-	I-Chemical
+2	I-Chemical
+(	I-Chemical
+5H	I-Chemical
+)	I-Chemical
+-	I-Chemical
+furanon	I-Chemical
+)	O
+COX	O
+-	O
+2	O
+inhibitors	O
+.	O
+
+METHODS	O
+:	O
+Drugs	O
+were	O
+separately	O
+,	O
+orally	O
+once	O
+daily	O
+dosed	O
+to	O
+pregnant	O
+rats	O
+from	O
+day	O
+8	O
+to	O
+21	O
+(	O
+GD1	O
+=	O
+plug	O
+day	O
+)	O
+.	O
+
+Doses	O
+were	O
+set	O
+at	O
+0	O
+.	O
+3	O
+,	O
+3	O
+.	O
+0	O
+and	O
+30	O
+.	O
+0mg	O
+/	O
+kg	O
+for	O
+piroxicam	B-Chemical
+and	O
+0	O
+.	O
+2	O
+,	O
+2	O
+.	O
+0	O
+and	O
+20	O
+.	O
+0mg	O
+/	O
+kg	O
+for	O
+DFU	B-Chemical
+.	O
+
+Fetuses	O
+were	O
+delivered	O
+on	O
+GD	O
+21	O
+and	O
+routinely	O
+examined	O
+.	O
+
+Comprehensive	O
+clinical	O
+and	O
+developmental	O
+measurements	O
+were	O
+done	O
+.	O
+
+The	O
+pooled	O
+statistical	O
+analysis	O
+for	O
+ventricular	B-Disease
+septal	I-Disease
+(	I-Disease
+VSD	I-Disease
+)	I-Disease
+and	I-Disease
+midline	I-Disease
+(	I-Disease
+MD	I-Disease
+)	I-Disease
+defects	I-Disease
+was	O
+performed	O
+for	O
+rat	O
+fetuses	O
+exposed	O
+to	O
+piroxicam	B-Chemical
+,	O
+selective	O
+and	O
+non	O
+-	O
+selective	O
+COX	O
+-	O
+2	O
+inhibitor	O
+based	O
+on	O
+present	O
+and	O
+historic	O
+data	O
+.	O
+
+RESULTS	O
+:	O
+Maternal	O
+toxicity	B-Disease
+,	O
+intrauterine	B-Disease
+growth	I-Disease
+retardation	I-Disease
+,	O
+and	O
+increase	B-Disease
+of	I-Disease
+external	I-Disease
+and	I-Disease
+skeletal	I-Disease
+variations	I-Disease
+were	O
+found	O
+in	O
+rats	O
+treated	O
+with	O
+the	O
+highest	O
+dose	O
+of	O
+piroxicam	B-Chemical
+.	O
+
+Decrease	O
+of	O
+fetal	O
+length	O
+was	O
+the	O
+only	O
+signs	O
+of	O
+the	O
+DFU	B-Chemical
+developmental	O
+toxicity	B-Disease
+observed	O
+in	O
+pups	O
+exposed	O
+to	O
+the	O
+highest	O
+compound	O
+dose	O
+.	O
+
+Lack	O
+of	O
+teratogenicity	O
+was	O
+found	O
+in	O
+piroxicam	B-Chemical
+and	O
+DFU	B-Chemical
+-	O
+exposed	O
+groups	O
+.	O
+
+Prenatal	O
+exposure	O
+to	O
+non	O
+-	O
+selective	O
+COX	O
+inhibitors	O
+increases	O
+the	O
+risk	O
+of	O
+VSD	O
+and	O
+MD	O
+when	O
+compared	O
+to	O
+historic	O
+control	O
+but	O
+not	O
+with	O
+selective	O
+COX	O
+-	O
+2	O
+inhibitors	O
+.	O
+
+CONCLUSION	O
+:	O
+Both	O
+selective	O
+and	O
+non	O
+-	O
+selective	O
+COX	O
+-	O
+2	O
+inhibitors	O
+were	O
+toxic	O
+for	O
+rats	O
+fetuses	O
+when	O
+administered	O
+in	O
+the	O
+highest	O
+dose	O
+.	O
+
+Unlike	O
+DFU	B-Chemical
+,	O
+piroxicam	B-Chemical
+was	O
+also	O
+highly	O
+toxic	O
+to	O
+the	O
+dams	O
+.	O
+
+Prenatal	O
+exposure	O
+to	O
+selective	O
+COX	O
+-	O
+2	O
+inhibitors	O
+does	O
+not	O
+increase	O
+the	O
+risk	O
+of	O
+ventricular	B-Disease
+septal	I-Disease
+and	I-Disease
+midline	I-Disease
+defects	I-Disease
+in	O
+rat	O
+when	O
+compared	O
+to	O
+non	O
+-	O
+selective	O
+drugs	O
+and	O
+historic	O
+control	O
+.	O
+
+Lone	O
+atrial	B-Disease
+fibrillation	I-Disease
+associated	O
+with	O
+creatine	B-Chemical
+monohydrate	O
+supplementation	O
+.	O
+
+Atrial	B-Disease
+fibrillation	I-Disease
+in	O
+young	O
+patients	O
+without	O
+structural	O
+heart	B-Disease
+disease	I-Disease
+is	O
+rare	O
+.	O
+
+Therefore	O
+,	O
+when	O
+the	O
+arrhythmia	B-Disease
+is	O
+present	O
+in	O
+this	O
+population	O
+,	O
+reversible	O
+causes	O
+must	O
+be	O
+identified	O
+and	O
+resolved	O
+.	O
+
+Thyroid	B-Disease
+disorders	I-Disease
+,	O
+illicit	O
+drug	O
+or	O
+stimulant	O
+use	O
+,	O
+and	O
+acute	B-Disease
+alcohol	I-Disease
+intoxication	I-Disease
+are	O
+among	O
+these	O
+causes	O
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+30	O
+-	O
+year	O
+-	O
+old	O
+Caucasian	O
+man	O
+who	O
+came	O
+to	O
+the	O
+emergency	O
+department	O
+in	O
+atrial	B-Disease
+fibrillation	I-Disease
+with	O
+rapid	O
+ventricular	O
+response	O
+.	O
+
+His	O
+medical	O
+history	O
+was	O
+unremarkable	O
+,	O
+except	O
+for	O
+minor	O
+fractures	B-Disease
+of	O
+the	O
+fingers	O
+and	O
+foot	O
+.	O
+
+Thyroid	O
+-	O
+stimulating	O
+hormone	O
+,	O
+magnesium	B-Chemical
+,	O
+and	O
+potassium	B-Chemical
+levels	O
+were	O
+within	O
+normal	O
+limits	O
+,	O
+urine	O
+drug	O
+screen	O
+was	O
+negative	O
+,	O
+and	O
+alcohol	B-Chemical
+use	O
+was	O
+denied	O
+.	O
+
+However	O
+,	O
+when	O
+the	O
+patient	O
+was	O
+questioned	O
+about	O
+use	O
+of	O
+herbal	O
+products	O
+and	O
+supplements	O
+,	O
+the	O
+use	O
+of	O
+creatine	B-Chemical
+monohydrate	O
+was	O
+revealed	O
+.	O
+
+The	O
+patient	O
+was	O
+admitted	O
+to	O
+the	O
+hospital	O
+,	O
+anticoagulated	O
+with	O
+unfractionated	O
+heparin	B-Chemical
+,	O
+and	O
+given	O
+intravenous	O
+diltiazem	B-Chemical
+for	O
+rate	O
+control	O
+and	O
+intravenous	O
+amiodarone	B-Chemical
+for	O
+rate	O
+and	O
+rhythm	O
+control	O
+.	O
+
+When	O
+discharged	O
+less	O
+than	O
+24	O
+hours	O
+later	O
+,	O
+he	O
+was	O
+receiving	O
+metoprolol	B-Chemical
+and	O
+aspirin	B-Chemical
+,	O
+with	O
+follow	O
+-	O
+up	O
+plans	O
+for	O
+echocardiography	O
+and	O
+nuclear	O
+imaging	O
+to	O
+assess	O
+perfusion	O
+.	O
+
+Exogenous	O
+creatine	B-Chemical
+is	O
+used	O
+by	O
+athletes	O
+to	O
+theoretically	O
+improve	O
+exercise	O
+performance	O
+.	O
+
+Vegetarians	O
+may	O
+also	O
+take	O
+creatine	B-Chemical
+to	O
+replace	O
+what	O
+they	O
+are	O
+not	O
+consuming	O
+from	O
+meat	O
+,	O
+fish	O
+,	O
+and	O
+other	O
+animal	O
+products	O
+.	O
+
+Previous	O
+anecdotal	O
+reports	O
+have	O
+linked	O
+creatine	B-Chemical
+to	O
+the	O
+development	O
+of	O
+arrhythmia	B-Disease
+.	O
+
+Clinicians	O
+must	O
+be	O
+diligent	O
+when	O
+interviewing	O
+patients	O
+about	O
+their	O
+drug	O
+therapy	O
+histories	O
+and	O
+include	O
+questions	O
+about	O
+their	O
+use	O
+of	O
+herbal	O
+products	O
+and	O
+dietary	O
+supplements	O
+.	O
+
+In	O
+addition	O
+,	O
+it	O
+is	O
+important	O
+to	O
+report	O
+adverse	O
+effects	O
+associated	O
+with	O
+frequently	O
+consumed	O
+supplements	O
+and	O
+herbal	O
+products	O
+to	O
+the	O
+Food	O
+and	O
+Drug	O
+Administration	O
+and	O
+in	O
+the	O
+literature	O
+.	O
+
+Seizures	B-Disease
+induced	O
+by	O
+the	O
+cocaine	B-Chemical
+metabolite	O
+benzoylecgonine	B-Chemical
+in	O
+rats	O
+.	O
+
+The	O
+half	O
+-	O
+life	O
+(	O
+t1	O
+/	O
+2	O
+)	O
+of	O
+cocaine	B-Chemical
+is	O
+relatively	O
+short	O
+,	O
+but	O
+some	O
+of	O
+the	O
+consequences	O
+of	O
+its	O
+use	O
+,	O
+such	O
+as	O
+seizures	B-Disease
+and	O
+strokes	B-Disease
+,	O
+can	O
+occur	O
+hours	O
+after	O
+exposure	O
+.	O
+
+This	O
+led	O
+us	O
+to	O
+hypothesize	O
+that	O
+a	O
+metabolite	O
+of	O
+cocaine	B-Chemical
+may	O
+be	O
+responsible	O
+for	O
+some	O
+of	O
+those	O
+delayed	O
+sequelae	O
+.	O
+
+We	O
+evaluated	O
+the	O
+potential	O
+of	O
+the	O
+major	O
+metabolite	O
+of	O
+cocaine	B-Chemical
+,	O
+benzoylecgonine	B-Chemical
+(	O
+BE	B-Chemical
+)	O
+,	O
+to	O
+cause	O
+seizures	B-Disease
+.	O
+
+Two	O
+separate	O
+equimolar	O
+doses	O
+(	O
+0	O
+.	O
+2	O
+and	O
+0	O
+.	O
+4	O
+mumol	O
+)	O
+of	O
+either	O
+cocaine	B-Chemical
+or	O
+BE	B-Chemical
+were	O
+injected	O
+ventricularly	O
+in	O
+unanesthetized	O
+juvenile	O
+rats	O
+.	O
+
+Treated	O
+rats	O
+were	O
+then	O
+evaluated	O
+for	O
+incidence	O
+,	O
+latency	O
+,	O
+and	O
+seizure	B-Disease
+pattern	O
+or	O
+for	O
+locomotor	O
+activity	O
+in	O
+animals	O
+without	O
+seizures	B-Disease
+.	O
+
+BE	B-Chemical
+-	O
+Induced	O
+seizures	B-Disease
+occurred	O
+more	O
+frequently	O
+and	O
+had	O
+significantly	O
+longer	O
+latencies	O
+than	O
+those	O
+induced	O
+by	O
+equimolar	O
+amounts	O
+of	O
+cocaine	B-Chemical
+.	O
+
+Whereas	O
+cocaine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+were	O
+best	O
+characterized	O
+as	O
+brief	O
+,	O
+generalized	O
+,	O
+and	O
+tonic	O
+and	O
+resulted	O
+in	O
+death	B-Disease
+,	O
+those	O
+induced	O
+by	O
+BE	B-Chemical
+were	O
+prolonged	O
+,	O
+often	O
+multiple	O
+and	O
+mixed	O
+in	O
+type	O
+,	O
+and	O
+rarely	O
+resulted	O
+in	O
+death	B-Disease
+.	O
+
+Electrical	O
+recordings	O
+from	O
+the	O
+hippocampus	O
+showed	O
+a	O
+rhythmic	O
+progression	O
+in	O
+EEG	O
+frequency	O
+and	O
+voltage	O
+with	O
+clinical	O
+seizure	B-Disease
+expression	O
+.	O
+
+BE	B-Chemical
+-	O
+Injected	O
+rats	O
+that	O
+did	O
+not	O
+have	O
+seizures	B-Disease
+had	O
+significantly	O
+more	O
+locomotor	O
+activity	O
+than	O
+cocaine	B-Chemical
+-	O
+injected	O
+animals	O
+without	O
+seizures	B-Disease
+.	O
+
+The	O
+finding	O
+that	O
+cocaine	B-Chemical
+-	O
+and	O
+BE	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+differ	O
+in	O
+several	O
+respects	O
+suggests	O
+more	O
+than	O
+one	O
+mechanism	O
+for	O
+cocaine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+and	O
+emphasizes	O
+the	O
+importance	O
+of	O
+a	O
+cocaine	B-Chemical
+metabolite	O
+,	O
+BE	B-Chemical
+.	O
+
+The	O
+selective	O
+5	O
+-	O
+HT6	O
+receptor	O
+antagonist	O
+Ro4368554	B-Chemical
+restores	O
+memory	O
+performance	O
+in	O
+cholinergic	O
+and	O
+serotonergic	O
+models	O
+of	O
+memory	B-Disease
+deficiency	I-Disease
+in	O
+the	O
+rat	O
+.	O
+
+Antagonists	O
+at	O
+serotonin	B-Chemical
+type	O
+6	O
+(	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+(	O
+6	O
+)	O
+)	O
+receptors	O
+show	O
+activity	O
+in	O
+models	O
+of	O
+learning	O
+and	O
+memory	O
+.	O
+
+Although	O
+the	O
+underlying	O
+mechanism	O
+(	O
+s	O
+)	O
+are	O
+not	O
+well	O
+understood	O
+,	O
+these	O
+effects	O
+may	O
+involve	O
+an	O
+increase	O
+in	O
+acetylcholine	B-Chemical
+(	O
+ACh	B-Chemical
+)	O
+levels	O
+.	O
+
+The	O
+present	O
+study	O
+sought	O
+to	O
+characterize	O
+the	O
+cognitive	O
+-	O
+enhancing	O
+effects	O
+of	O
+the	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+(	O
+6	O
+)	O
+antagonist	O
+Ro4368554	B-Chemical
+(	O
+3	B-Chemical
+-	I-Chemical
+benzenesulfonyl	I-Chemical
+-	I-Chemical
+7	I-Chemical
+-	I-Chemical
+(	I-Chemical
+4	I-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+piperazin	I-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+yl	I-Chemical
+)	I-Chemical
+1H	I-Chemical
+-	I-Chemical
+indole	I-Chemical
+)	O
+in	O
+a	O
+rat	O
+object	O
+recognition	O
+task	O
+employing	O
+a	O
+cholinergic	O
+(	O
+scopolamine	B-Chemical
+pretreatment	O
+)	O
+and	O
+a	O
+serotonergic	O
+-	O
+(	O
+tryptophan	B-Chemical
+(	O
+TRP	B-Chemical
+)	O
+depletion	O
+)	O
+deficient	O
+model	O
+,	O
+and	O
+compared	O
+its	O
+pattern	O
+of	O
+action	O
+with	O
+that	O
+of	O
+the	O
+acetylcholinesterase	O
+inhibitor	O
+metrifonate	B-Chemical
+.	O
+
+Initial	O
+testing	O
+in	O
+a	O
+time	O
+-	O
+dependent	O
+forgetting	O
+task	O
+employing	O
+a	O
+24	O
+-	O
+h	O
+delay	O
+between	O
+training	O
+and	O
+testing	O
+showed	O
+that	O
+metrifonate	B-Chemical
+improved	O
+object	O
+recognition	O
+(	O
+at	O
+10	O
+and	O
+30	O
+mg	O
+/	O
+kg	O
+,	O
+p	O
+.	O
+o	O
+.	O
+)	O
+,	O
+whereas	O
+Ro4368554	B-Chemical
+was	O
+inactive	O
+.	O
+
+Both	O
+,	O
+Ro4368554	B-Chemical
+(	O
+3	O
+and	O
+10	O
+mg	O
+/	O
+kg	O
+,	O
+intraperitoneally	O
+(	O
+i	O
+.	O
+p	O
+.	O
+)	O
+)	O
+and	O
+metrifonate	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+,	O
+p	O
+.	O
+o	O
+.	O
+,	O
+respectively	O
+)	O
+reversed	O
+memory	B-Disease
+deficits	I-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+and	O
+TRP	B-Chemical
+depletion	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+,	O
+and	O
+3	O
+mg	O
+/	O
+kg	O
+,	O
+p	O
+.	O
+o	O
+.	O
+,	O
+respectively	O
+)	O
+.	O
+
+In	O
+conclusion	O
+,	O
+although	O
+Ro4368554	B-Chemical
+did	O
+not	O
+improve	O
+a	O
+time	O
+-	O
+related	O
+retention	O
+deficit	O
+,	O
+it	O
+reversed	O
+a	O
+cholinergic	O
+and	O
+a	O
+serotonergic	O
+memory	B-Disease
+deficit	I-Disease
+,	O
+suggesting	O
+that	O
+both	O
+mechanisms	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+facilitation	O
+of	O
+object	O
+memory	O
+by	O
+Ro4368554	B-Chemical
+and	O
+,	O
+possibly	O
+,	O
+other	O
+5	B-Chemical
+-	I-Chemical
+HT	I-Chemical
+(	O
+6	O
+)	O
+receptor	O
+antagonists	O
+.	O
+
+Evaluation	O
+of	O
+the	O
+anticocaine	O
+monoclonal	O
+antibody	O
+GNC92H2	B-Chemical
+as	O
+an	O
+immunotherapy	O
+for	O
+cocaine	B-Disease
+overdose	I-Disease
+.	O
+
+The	O
+illicit	O
+use	O
+of	O
+cocaine	B-Chemical
+continues	O
+in	O
+epidemic	O
+proportions	O
+and	O
+treatment	O
+for	O
+cocaine	B-Disease
+overdose	I-Disease
+remains	O
+elusive	O
+.	O
+
+Current	O
+protein	O
+-	O
+based	O
+technology	O
+offers	O
+a	O
+new	O
+therapeutic	O
+venue	O
+by	O
+which	O
+antibodies	O
+bind	O
+the	O
+drug	O
+in	O
+the	O
+blood	O
+stream	O
+,	O
+inactivating	O
+its	O
+toxic	O
+effects	O
+.	O
+
+The	O
+therapeutic	O
+potential	O
+of	O
+the	O
+anticocaine	O
+antibody	O
+GNC92H2	B-Chemical
+was	O
+examined	O
+using	O
+a	O
+model	O
+of	O
+cocaine	B-Disease
+overdose	I-Disease
+.	O
+
+Swiss	O
+albino	O
+mice	O
+prepared	O
+with	O
+intrajugular	O
+catheters	O
+were	O
+tested	O
+in	O
+photocell	O
+cages	O
+after	O
+administration	O
+of	O
+93	O
+mg	O
+/	O
+kg	O
+(	O
+LD50	O
+)	O
+of	O
+cocaine	B-Chemical
+and	O
+GNC92H2	B-Chemical
+infusions	O
+ranging	O
+from	O
+30	O
+to	O
+190	O
+mg	O
+/	O
+kg	O
+.	O
+
+GNC92H2	B-Chemical
+was	O
+delivered	O
+30	O
+min	O
+before	O
+,	O
+concomitantly	O
+or	O
+3	O
+min	O
+after	O
+cocaine	B-Chemical
+treatment	O
+.	O
+
+Significant	O
+blockade	O
+of	O
+cocaine	B-Chemical
+toxicity	B-Disease
+was	O
+observed	O
+with	O
+the	O
+higher	O
+dose	O
+of	O
+GNC92H2	B-Chemical
+(	O
+190	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+where	O
+premorbid	O
+behaviors	O
+were	O
+reduced	O
+up	O
+to	O
+40	O
+%	O
+,	O
+seizures	B-Disease
+up	O
+to	O
+77	O
+%	O
+and	O
+death	B-Disease
+by	O
+72	O
+%	O
+.	O
+
+Importantly	O
+,	O
+GNC92H2	B-Chemical
+prevented	O
+death	B-Disease
+even	O
+post	O
+-	O
+cocaine	B-Chemical
+injection	O
+.	O
+
+The	O
+results	O
+support	O
+the	O
+important	O
+potential	O
+of	O
+GNC92H2	B-Chemical
+as	O
+a	O
+therapeutic	O
+tool	O
+against	O
+cocaine	B-Disease
+overdose	I-Disease
+.	O
+
+Electrocardiographic	O
+evidence	O
+of	O
+myocardial	B-Disease
+injury	I-Disease
+in	O
+psychiatrically	O
+hospitalized	O
+cocaine	B-Chemical
+abusers	O
+.	O
+
+The	O
+electrocardiograms	O
+(	O
+ECG	O
+)	O
+of	O
+99	O
+cocaine	B-Chemical
+-	O
+abusing	O
+patients	O
+were	O
+compared	O
+with	O
+the	O
+ECGs	O
+of	O
+50	O
+schizophrenic	B-Disease
+controls	O
+.	O
+
+Eleven	O
+of	O
+the	O
+cocaine	B-Chemical
+abusers	O
+and	O
+none	O
+of	O
+the	O
+controls	O
+had	O
+ECG	O
+evidence	O
+of	O
+significant	O
+myocardial	B-Disease
+injury	I-Disease
+defined	O
+as	O
+myocardial	B-Disease
+infarction	I-Disease
+,	O
+ischemia	B-Disease
+,	O
+and	O
+bundle	B-Disease
+branch	I-Disease
+block	I-Disease
+.	O
+
+Behavioral	O
+effects	O
+of	O
+urotensin	B-Chemical
+-	I-Chemical
+II	I-Chemical
+centrally	O
+administered	O
+in	O
+mice	O
+.	O
+
+Urotensin	B-Chemical
+-	I-Chemical
+II	I-Chemical
+(	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+)	O
+receptors	O
+are	O
+widely	O
+distributed	O
+in	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Intracerebroventricular	O
+(	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+)	O
+injection	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+causes	O
+hypertension	B-Disease
+and	O
+bradycardia	B-Disease
+and	O
+stimulates	O
+prolactin	O
+and	O
+thyrotropin	O
+secretion	O
+.	O
+
+However	O
+,	O
+the	O
+behavioral	O
+effects	O
+of	O
+centrally	O
+administered	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+have	O
+received	O
+little	O
+attention	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+tested	O
+the	O
+effects	O
+of	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+injections	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+on	O
+behavioral	O
+,	O
+metabolic	O
+,	O
+and	O
+endocrine	O
+responses	O
+in	O
+mice	O
+.	O
+
+Administration	O
+of	O
+graded	O
+doses	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+(	O
+1	O
+-	O
+10	O
+,	O
+000	O
+ng	O
+/	O
+mouse	O
+)	O
+provoked	O
+:	O
+(	O
+1	O
+)	O
+a	O
+dose	O
+-	O
+dependent	O
+reduction	O
+in	O
+the	O
+number	O
+of	O
+head	O
+dips	O
+in	O
+the	O
+hole	O
+-	O
+board	O
+test	O
+;	O
+(	O
+2	O
+)	O
+a	O
+dose	O
+-	O
+dependent	O
+reduction	O
+in	O
+the	O
+number	O
+of	O
+entries	O
+in	O
+the	O
+white	O
+chamber	O
+in	O
+the	O
+black	O
+-	O
+and	O
+-	O
+white	O
+compartment	O
+test	O
+,	O
+and	O
+in	O
+the	O
+number	O
+of	O
+entries	O
+in	O
+the	O
+central	O
+platform	O
+and	O
+open	O
+arms	O
+in	O
+the	O
+plus	O
+-	O
+maze	O
+test	O
+;	O
+and	O
+(	O
+3	O
+)	O
+a	O
+dose	O
+-	O
+dependent	O
+increase	O
+in	O
+the	O
+duration	O
+of	O
+immobility	O
+in	O
+the	O
+forced	O
+-	O
+swimming	O
+test	O
+and	O
+tail	O
+suspension	O
+test	O
+.	O
+
+Intracerebroventricular	O
+injection	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+also	O
+caused	O
+an	O
+increase	O
+in	O
+:	O
+food	O
+intake	O
+at	O
+doses	O
+of	O
+100	O
+and	O
+1	O
+,	O
+000	O
+ng	O
+/	O
+mouse	O
+,	O
+water	O
+intake	O
+at	O
+doses	O
+of	O
+100	O
+-	O
+10	O
+,	O
+000	O
+ng	O
+/	O
+mouse	O
+,	O
+and	O
+horizontal	O
+locomotion	O
+activity	O
+at	O
+a	O
+dose	O
+of	O
+10	O
+,	O
+000	O
+ng	O
+/	O
+mouse	O
+.	O
+
+Whatever	O
+was	O
+the	O
+dose	O
+,	O
+the	O
+central	O
+administration	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+had	O
+no	O
+effect	O
+on	O
+body	O
+temperature	O
+,	O
+nociception	O
+,	O
+apomorphine	B-Chemical
+-	O
+induced	O
+penile	B-Disease
+erection	I-Disease
+and	O
+climbing	O
+behavior	O
+,	O
+and	O
+stress	O
+-	O
+induced	O
+plasma	O
+corticosterone	B-Chemical
+level	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+present	O
+study	O
+demonstrates	O
+that	O
+the	O
+central	O
+injection	O
+of	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+at	O
+doses	O
+of	O
+1	O
+-	O
+10	O
+,	O
+000	O
+ng	O
+/	O
+mouse	O
+induces	O
+anxiogenic	O
+-	O
+and	O
+depressant	O
+-	O
+like	O
+effects	O
+in	O
+mouse	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+U	B-Chemical
+-	I-Chemical
+II	I-Chemical
+may	O
+be	O
+involved	O
+in	O
+some	O
+aspects	O
+of	O
+psychiatric	B-Disease
+disorders	I-Disease
+.	O
+
+Learning	O
+of	O
+rats	O
+under	O
+amnesia	B-Disease
+caused	O
+by	O
+pentobarbital	B-Chemical
+.	O
+
+Dissociated	O
+learning	O
+of	O
+rats	O
+in	O
+the	O
+normal	O
+state	O
+and	O
+the	O
+state	O
+of	O
+amnesia	B-Disease
+produced	O
+by	O
+pentobarbital	B-Chemical
+(	O
+15	O
+mg	O
+/	O
+kg	O
+,	O
+ip	O
+)	O
+was	O
+carried	O
+out	O
+.	O
+
+Rats	O
+were	O
+trained	O
+to	O
+approach	O
+a	O
+shelf	O
+where	O
+they	O
+received	O
+food	O
+reinforcement	O
+.	O
+
+In	O
+Group	O
+1	O
+the	O
+rats	O
+were	O
+trained	O
+under	O
+the	O
+influence	O
+of	O
+pentobarbital	B-Chemical
+to	O
+run	O
+to	O
+the	O
+same	O
+shelf	O
+as	O
+in	O
+the	O
+normal	O
+state	O
+.	O
+
+In	O
+Group	O
+2	O
+the	O
+rats	O
+were	O
+trained	O
+to	O
+approach	O
+different	O
+shelves	O
+in	O
+different	O
+drug	O
+states	O
+.	O
+
+It	O
+was	O
+shown	O
+that	O
+memory	B-Disease
+dissociation	I-Disease
+occurred	O
+in	O
+both	O
+groups	O
+.	O
+
+Differences	O
+in	O
+the	O
+parameters	O
+of	O
+training	O
+under	O
+the	O
+influence	O
+of	O
+pentobarbital	B-Chemical
+between	O
+Groups	O
+1	O
+and	O
+2	O
+were	O
+revealed	O
+.	O
+
+These	O
+findings	O
+show	O
+that	O
+the	O
+brain	O
+-	O
+dissociated	O
+state	O
+induced	O
+by	O
+pentobarbital	B-Chemical
+is	O
+formed	O
+with	O
+the	O
+participation	O
+of	O
+the	O
+mechanisms	O
+of	O
+information	O
+perception	O
+.	O
+
+The	O
+effects	O
+of	O
+short	O
+-	O
+term	O
+raloxifene	B-Chemical
+therapy	O
+on	O
+fibrinolysis	O
+markers	O
+:	O
+TAFI	O
+,	O
+tPA	O
+,	O
+and	O
+PAI	O
+-	O
+1	O
+.	O
+
+BACKGROUND	O
+:	O
+Markers	O
+of	O
+fibrinolysis	O
+,	O
+thrombin	O
+-	O
+activatable	O
+fibrinolysis	O
+inhibitor	O
+(	O
+TAFI	O
+)	O
+,	O
+tissue	O
+-	O
+type	O
+plasminogen	O
+activator	O
+(	O
+tPA	O
+)	O
+,	O
+and	O
+plasminogen	O
+activator	O
+inhibitor	O
+-	O
+1	O
+(	O
+PAI	O
+-	O
+1	O
+)	O
+levels	O
+were	O
+studied	O
+for	O
+the	O
+evaluation	O
+of	O
+short	O
+-	O
+term	O
+effects	O
+of	O
+raloxifene	B-Chemical
+administration	O
+in	O
+postmenopausal	O
+women	O
+.	O
+
+METHODS	O
+:	O
+Thirty	O
+-	O
+nine	O
+postmenopausal	O
+women	O
+with	O
+osteopenia	B-Disease
+or	O
+osteoporosis	B-Disease
+were	O
+included	O
+in	O
+this	O
+prospective	O
+,	O
+controlled	O
+clinical	O
+study	O
+.	O
+
+Twenty	O
+-	O
+five	O
+women	O
+were	O
+given	O
+raloxifene	B-Chemical
+hydrochloride	I-Chemical
+(	O
+60	O
+mg	O
+/	O
+day	O
+)	O
+plus	O
+calcium	B-Chemical
+(	O
+500	O
+mg	O
+/	O
+day	O
+)	O
+.	O
+
+Age	O
+-	O
+matched	O
+controls	O
+(	O
+n	O
+=	O
+14	O
+)	O
+were	O
+given	O
+only	O
+calcium	B-Chemical
+.	O
+
+Plasma	O
+TAFI	O
+,	O
+tPA	O
+,	O
+and	O
+PAI	O
+-	O
+1	O
+antigen	O
+levels	O
+were	O
+measured	O
+at	O
+baseline	O
+and	O
+after	O
+3	O
+months	O
+of	O
+treatment	O
+by	O
+commercially	O
+available	O
+ELISA	O
+kits	O
+.	O
+
+Variations	O
+of	O
+individuals	O
+were	O
+assessed	O
+by	O
+Wilcoxon	O
+'	O
+s	O
+test	O
+.	O
+
+Relationship	O
+between	O
+those	O
+markers	O
+and	O
+demographic	O
+characteristics	O
+were	O
+investigated	O
+.	O
+
+RESULTS	O
+:	O
+Three	O
+months	O
+of	O
+raloxifene	B-Chemical
+treatment	O
+was	O
+associated	O
+with	O
+a	O
+significant	O
+decrease	O
+in	O
+the	O
+plasma	O
+TAFI	O
+antigen	O
+concentrations	O
+(	O
+16	O
+%	O
+change	O
+,	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+a	O
+significant	O
+increase	O
+in	O
+tPA	O
+antigen	O
+concentrations	O
+(	O
+25	O
+%	O
+change	O
+,	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+A	O
+significant	O
+correlation	O
+was	O
+found	O
+between	O
+baseline	O
+TAFI	O
+antigen	O
+concentrations	O
+and	O
+the	O
+duration	O
+of	O
+amenorrhea	B-Disease
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+;	O
+r	O
+=	O
+0	O
+.	O
+33	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+We	O
+suggest	O
+that	O
+the	O
+increased	O
+risk	O
+of	O
+venous	B-Disease
+thromboembolism	I-Disease
+due	O
+to	O
+raloxifene	B-Chemical
+treatment	O
+may	O
+be	O
+related	O
+to	O
+increased	O
+tPA	O
+levels	O
+,	O
+but	O
+not	O
+TAFI	O
+levels	O
+.	O
+
+Valproate	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+.	O
+
+Valproate	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+is	O
+a	O
+rare	O
+syndrome	O
+that	O
+may	O
+manifest	O
+in	O
+otherwise	O
+normal	O
+epileptic	B-Disease
+individuals	O
+.	O
+
+It	O
+may	O
+even	O
+present	O
+in	O
+patients	O
+who	O
+have	O
+tolerated	O
+this	O
+medicine	O
+well	O
+in	O
+the	O
+past	O
+.	O
+
+It	O
+is	O
+usually	O
+but	O
+not	O
+necessarily	O
+associated	O
+with	O
+hyperammonemia	B-Disease
+.	O
+
+The	O
+EEG	O
+shows	O
+characteristic	O
+triphasic	O
+waves	O
+in	O
+most	O
+patients	O
+with	O
+this	O
+complication	O
+.	O
+
+A	O
+case	O
+of	O
+valproate	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+is	O
+presented	O
+.	O
+
+The	O
+problems	O
+in	O
+diagnosing	O
+this	O
+condition	O
+are	O
+subsequently	O
+discussed	O
+.	O
+
+Recurrent	O
+dysphonia	B-Disease
+and	O
+acitretin	B-Chemical
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+woman	O
+complaining	O
+of	O
+dysphonia	B-Disease
+while	O
+she	O
+was	O
+treated	O
+by	O
+acitretin	B-Chemical
+.	O
+
+Her	O
+symptoms	O
+totally	O
+regressed	O
+after	O
+drug	O
+withdrawal	O
+and	O
+reappeared	O
+when	O
+acitretin	B-Chemical
+was	O
+reintroduced	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+case	O
+of	O
+acitretin	B-Chemical
+-	O
+induced	O
+dysphonia	B-Disease
+.	O
+
+This	O
+effect	O
+may	O
+be	O
+related	O
+to	O
+the	O
+pharmacological	O
+effect	O
+of	O
+this	O
+drug	O
+on	O
+mucous	O
+membranes	O
+.	O
+
+Nitro	B-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+methyl	I-Chemical
+ester	I-Chemical
+:	O
+a	O
+potential	O
+protector	O
+against	O
+gentamicin	B-Chemical
+ototoxicity	B-Disease
+.	O
+
+The	O
+nitric	B-Chemical
+oxide	I-Chemical
+(	O
+NO	B-Chemical
+)	O
+inhibitor	O
+nitro	B-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+arginine	I-Chemical
+methyl	I-Chemical
+ester	I-Chemical
+(	O
+L	B-Chemical
+-	I-Chemical
+NAME	I-Chemical
+)	O
+may	O
+act	O
+as	O
+an	O
+otoprotectant	O
+against	O
+high	B-Disease
+-	I-Disease
+frequency	I-Disease
+hearing	I-Disease
+loss	I-Disease
+caused	O
+by	O
+gentamicin	B-Chemical
+,	O
+but	O
+further	O
+studies	O
+are	O
+needed	O
+to	O
+confirm	O
+this	O
+.	O
+Aminoglycoside	B-Chemical
+antibiotics	O
+are	O
+still	O
+widely	O
+used	O
+by	O
+virtue	O
+of	O
+their	O
+efficacy	O
+and	O
+low	O
+cost	O
+.	O
+
+Their	O
+ototoxicity	B-Disease
+is	O
+a	O
+serious	O
+health	O
+problem	O
+and	O
+,	O
+as	O
+their	O
+ototoxic	B-Disease
+mechanism	O
+involves	O
+the	O
+production	O
+of	O
+NO	B-Chemical
+,	O
+we	O
+need	O
+to	O
+assess	O
+the	O
+use	O
+of	O
+NO	B-Chemical
+inhibitors	O
+for	O
+the	O
+prevention	O
+of	O
+aminoglycoside	B-Chemical
+-	O
+induced	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+.	O
+
+In	O
+this	O
+experimental	O
+study	O
+we	O
+used	O
+30	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+,	O
+27	O
+of	O
+which	O
+had	O
+gentamicin	B-Chemical
+instilled	O
+into	O
+the	O
+middle	O
+ear	O
+.	O
+
+The	O
+otoprotectant	O
+L	B-Chemical
+-	I-Chemical
+NAME	I-Chemical
+was	O
+administered	O
+topically	O
+to	O
+12	O
+/	O
+27	O
+animals	O
+.	O
+
+Its	O
+effect	O
+was	O
+determined	O
+in	O
+terms	O
+of	O
+attenuation	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+,	O
+measured	O
+by	O
+shifts	O
+in	O
+the	O
+auditory	O
+brainstem	O
+response	O
+threshold	O
+.	O
+
+L	B-Chemical
+-	I-Chemical
+NAME	I-Chemical
+reduced	O
+gentamicin	B-Chemical
+-	O
+induced	O
+hearing	B-Disease
+loss	I-Disease
+in	O
+the	O
+high	O
+-	O
+frequency	O
+range	O
+,	O
+but	O
+gave	O
+no	O
+protection	O
+in	O
+the	O
+middle	O
+or	O
+low	O
+frequencies	O
+.	O
+
+Safety	O
+profile	O
+of	O
+a	O
+nicotine	B-Chemical
+lozenge	O
+compared	O
+with	O
+that	O
+of	O
+nicotine	B-Chemical
+gum	O
+in	O
+adult	O
+smokers	O
+with	O
+underlying	O
+medical	O
+conditions	O
+:	O
+a	O
+12	O
+-	O
+week	O
+,	O
+randomized	O
+,	O
+open	O
+-	O
+label	O
+study	O
+.	O
+
+BACKGROUND	O
+:	O
+Nicotine	B-Chemical
+polacrilex	O
+lozenges	O
+deliver	O
+25	O
+%	O
+to	O
+27	O
+%	O
+more	O
+nicotine	B-Chemical
+compared	O
+with	O
+equivalent	O
+doses	O
+of	O
+nicotine	B-Chemical
+polacrilex	O
+gum	O
+.	O
+
+The	O
+increased	O
+nicotine	B-Chemical
+exposure	O
+from	O
+the	O
+lozenge	O
+has	O
+raised	O
+questions	O
+about	O
+the	O
+relative	O
+safety	O
+of	O
+the	O
+lozenge	O
+and	O
+gum	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+compare	O
+the	O
+safety	O
+profiles	O
+of	O
+the	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+lozenge	O
+and	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+gum	O
+in	O
+smokers	O
+with	O
+selected	O
+label	O
+-	O
+restricted	O
+diseases	O
+.	O
+
+METHODS	O
+:	O
+This	O
+was	O
+a	O
+multicenter	O
+,	O
+randomized	O
+,	O
+open	O
+-	O
+label	O
+study	O
+in	O
+adult	O
+smokers	O
+with	O
+heart	B-Disease
+disease	I-Disease
+,	O
+hypertension	B-Disease
+not	O
+controlled	O
+by	O
+medication	O
+,	O
+and	O
+/	O
+or	O
+diabetes	B-Disease
+mellitus	I-Disease
+.	O
+
+Patients	O
+were	O
+randomized	O
+in	O
+a	O
+1	O
+:	O
+1	O
+ratio	O
+to	O
+receive	O
+the	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+lozenge	O
+or	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+gum	O
+.	O
+
+Safety	O
+assessments	O
+were	O
+made	O
+at	O
+baseline	O
+and	O
+at	O
+2	O
+,	O
+4	O
+,	O
+6	O
+,	O
+and	O
+12	O
+weeks	O
+after	O
+the	O
+start	O
+of	O
+product	O
+use	O
+.	O
+
+RESULTS	O
+:	O
+Nine	O
+hundred	O
+one	O
+patients	O
+were	O
+randomized	O
+to	O
+treatment	O
+,	O
+447	O
+who	O
+received	O
+the	O
+lozenge	O
+and	O
+454	O
+who	O
+received	O
+the	O
+gum	O
+(	O
+safety	O
+population	O
+)	O
+.	O
+
+The	O
+majority	O
+were	O
+women	O
+(	O
+52	O
+.	O
+7	O
+%	O
+)	O
+.	O
+
+Patients	O
+'	O
+mean	O
+age	O
+was	O
+53	O
+.	O
+9	O
+years	O
+,	O
+their	O
+mean	O
+weight	O
+was	O
+193	O
+.	O
+9	O
+pounds	O
+,	O
+and	O
+they	O
+smoked	O
+a	O
+mean	O
+of	O
+25	O
+.	O
+2	O
+cigarettes	O
+per	O
+day	O
+at	O
+baseline	O
+.	O
+
+Five	O
+hundred	O
+fifty	O
+-	O
+three	O
+patients	O
+,	O
+264	O
+taking	O
+the	O
+lozenge	O
+and	O
+289	O
+taking	O
+the	O
+gum	O
+,	O
+used	O
+the	O
+study	O
+product	O
+for	O
+>	O
+or	O
+=	O
+4	O
+days	O
+per	O
+week	O
+during	O
+the	O
+first	O
+2	O
+weeks	O
+(	O
+evaluable	O
+population	O
+)	O
+.	O
+
+The	O
+nicotine	B-Chemical
+lozenge	O
+and	O
+nicotine	B-Chemical
+gum	O
+were	O
+equally	O
+well	O
+tolerated	O
+,	O
+despite	O
+increased	O
+nicotine	B-Chemical
+exposure	O
+from	O
+the	O
+lozenge	O
+.	O
+
+The	O
+incidence	O
+of	O
+adverse	O
+events	O
+in	O
+the	O
+2	O
+groups	O
+was	O
+similar	O
+during	O
+the	O
+first	O
+2	O
+weeks	O
+of	O
+product	O
+use	O
+(	O
+evaluation	O
+population	O
+:	O
+55	O
+.	O
+3	O
+%	O
+lozenge	O
+,	O
+54	O
+.	O
+7	O
+%	O
+gum	O
+)	O
+,	O
+as	O
+well	O
+as	O
+during	O
+the	O
+entire	O
+study	O
+(	O
+safety	O
+population	O
+:	O
+63	O
+.	O
+8	O
+%	O
+and	O
+58	O
+.	O
+6	O
+%	O
+,	O
+respectively	O
+)	O
+.	O
+
+Stratification	O
+of	O
+patients	O
+by	O
+sex	O
+,	O
+age	O
+,	O
+extent	O
+of	O
+concurrent	O
+smoking	O
+,	O
+extent	O
+of	O
+product	O
+use	O
+,	O
+and	O
+severity	O
+of	O
+adverse	O
+events	O
+revealed	O
+no	O
+clinically	O
+significant	O
+differences	O
+between	O
+the	O
+lozenge	O
+and	O
+gum	O
+.	O
+
+The	O
+most	O
+common	O
+adverse	O
+events	O
+were	O
+nausea	B-Disease
+(	O
+17	O
+.	O
+2	O
+%	O
+and	O
+16	O
+.	O
+1	O
+%	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+-	O
+3	O
+.	O
+7	O
+to	O
+6	O
+.	O
+0	O
+)	O
+,	O
+hiccups	B-Disease
+(	O
+10	O
+.	O
+7	O
+%	O
+and	O
+6	O
+.	O
+6	O
+%	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+0	O
+.	O
+5	O
+to	O
+7	O
+.	O
+8	O
+)	O
+,	O
+and	O
+headache	B-Disease
+(	O
+8	O
+.	O
+7	O
+%	O
+and	O
+9	O
+.	O
+9	O
+%	O
+;	O
+95	O
+%	O
+Cl	O
+,	O
+-	O
+5	O
+.	O
+0	O
+to	O
+2	O
+.	O
+6	O
+)	O
+.	O
+
+Serious	O
+adverse	O
+events	O
+were	O
+reported	O
+in	O
+11	O
+and	O
+13	O
+patients	O
+in	O
+the	O
+respective	O
+groups	O
+.	O
+
+Fewer	O
+than	O
+6	O
+%	O
+of	O
+patients	O
+in	O
+either	O
+group	O
+were	O
+considered	O
+by	O
+the	O
+investigator	O
+to	O
+have	O
+a	O
+worsening	O
+of	O
+their	O
+overall	O
+disease	O
+condition	O
+during	O
+the	O
+study	O
+.	O
+
+The	O
+majority	O
+of	O
+patients	O
+(	O
+>	O
+60	O
+%	O
+)	O
+experienced	O
+no	O
+change	O
+in	O
+their	O
+disease	O
+status	O
+from	O
+baseline	O
+.	O
+
+CONCLUSION	O
+:	O
+The	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+lozenge	O
+and	O
+4	O
+-	O
+mg	O
+nicotine	B-Chemical
+gum	O
+had	O
+comparable	O
+safety	O
+profiles	O
+in	O
+these	O
+patients	O
+with	O
+label	O
+-	O
+restricted	O
+medical	O
+conditions	O
+.	O
+
+Pharmacological	O
+modulation	O
+of	O
+pain	B-Disease
+-	O
+related	O
+brain	O
+activity	O
+during	O
+normal	O
+and	O
+central	O
+sensitization	O
+states	O
+in	O
+humans	O
+.	O
+
+Abnormal	O
+processing	O
+of	O
+somatosensory	O
+inputs	O
+in	O
+the	O
+central	O
+nervous	O
+system	O
+(	O
+central	O
+sensitization	O
+)	O
+is	O
+the	O
+mechanism	O
+accounting	O
+for	O
+the	O
+enhanced	O
+pain	B-Disease
+sensitivity	O
+in	O
+the	O
+skin	O
+surrounding	O
+tissue	B-Disease
+injury	I-Disease
+(	O
+secondary	B-Disease
+hyperalgesia	I-Disease
+)	O
+.	O
+
+Secondary	B-Disease
+hyperalgesia	I-Disease
+shares	O
+clinical	O
+characteristics	O
+with	O
+neurogenic	B-Disease
+hyperalgesia	I-Disease
+in	O
+patients	O
+with	O
+neuropathic	B-Disease
+pain	I-Disease
+.	O
+
+Abnormal	O
+brain	O
+responses	O
+to	O
+somatosensory	O
+stimuli	O
+have	O
+been	O
+found	O
+in	O
+patients	O
+with	O
+hyperalgesia	B-Disease
+as	O
+well	O
+as	O
+in	O
+normal	O
+subjects	O
+during	O
+experimental	O
+central	O
+sensitization	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+assess	O
+the	O
+effects	O
+of	O
+gabapentin	B-Chemical
+,	O
+a	O
+drug	O
+effective	O
+in	O
+neuropathic	B-Disease
+pain	I-Disease
+patients	O
+,	O
+on	O
+brain	O
+processing	O
+of	O
+nociceptive	O
+information	O
+in	O
+normal	O
+and	O
+central	O
+sensitization	O
+states	O
+.	O
+
+Using	O
+functional	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+fMRI	O
+)	O
+in	O
+normal	O
+volunteers	O
+,	O
+we	O
+studied	O
+the	O
+gabapentin	B-Chemical
+-	O
+induced	O
+modulation	O
+of	O
+brain	O
+activity	O
+in	O
+response	O
+to	O
+nociceptive	O
+mechanical	O
+stimulation	O
+of	O
+normal	O
+skin	O
+and	O
+capsaicin	B-Chemical
+-	O
+induced	O
+secondary	B-Disease
+hyperalgesia	I-Disease
+.	O
+
+The	O
+dose	O
+of	O
+gabapentin	B-Chemical
+was	O
+1	O
+,	O
+800	O
+mg	O
+per	O
+os	O
+,	O
+in	O
+a	O
+single	O
+administration	O
+.	O
+
+We	O
+found	O
+that	O
+(	O
+i	O
+)	O
+gabapentin	B-Chemical
+reduced	O
+the	O
+activations	O
+in	O
+the	O
+bilateral	O
+operculoinsular	O
+cortex	O
+,	O
+independently	O
+of	O
+the	O
+presence	O
+of	O
+central	O
+sensitization	O
+;	O
+(	O
+ii	O
+)	O
+gabapentin	B-Chemical
+reduced	O
+the	O
+activation	O
+in	O
+the	O
+brainstem	O
+,	O
+only	O
+during	O
+central	O
+sensitization	O
+;	O
+(	O
+iii	O
+)	O
+gabapentin	B-Chemical
+suppressed	O
+stimulus	O
+-	O
+induced	O
+deactivations	O
+,	O
+only	O
+during	O
+central	O
+sensitization	O
+;	O
+this	O
+effect	O
+was	O
+more	O
+robust	O
+than	O
+the	O
+effect	O
+on	O
+brain	O
+activation	O
+.	O
+
+The	O
+observed	O
+drug	O
+-	O
+induced	O
+effects	O
+were	O
+not	O
+due	O
+to	O
+changes	O
+in	O
+the	O
+baseline	O
+fMRI	O
+signal	O
+.	O
+
+These	O
+findings	O
+indicate	O
+that	O
+gabapentin	B-Chemical
+has	O
+a	O
+measurable	O
+antinociceptive	O
+effect	O
+and	O
+a	O
+stronger	O
+antihyperalgesic	O
+effect	O
+most	O
+evident	O
+in	O
+the	O
+brain	O
+areas	O
+undergoing	O
+deactivation	O
+,	O
+thus	O
+supporting	O
+the	O
+concept	O
+that	O
+gabapentin	B-Chemical
+is	O
+more	O
+effective	O
+in	O
+modulating	O
+nociceptive	O
+transmission	O
+when	O
+central	O
+sensitization	O
+is	O
+present	O
+.	O
+
+Investigation	O
+of	O
+mitochondrial	O
+involvement	O
+in	O
+the	O
+experimental	O
+model	O
+of	O
+epilepsy	B-Disease
+induced	O
+by	O
+pilocarpine	B-Chemical
+.	O
+
+Mitochondrial	B-Disease
+abnormalities	I-Disease
+have	O
+been	O
+associated	O
+with	O
+several	O
+aspects	O
+of	O
+epileptogenesis	O
+,	O
+such	O
+as	O
+energy	O
+generation	O
+,	O
+control	O
+of	O
+cell	O
+death	B-Disease
+,	O
+neurotransmitter	O
+synthesis	O
+,	O
+and	O
+free	O
+radical	O
+(	O
+FR	O
+)	O
+production	O
+.	O
+
+Increased	O
+production	O
+of	O
+FRs	O
+may	O
+cause	O
+mtDNA	O
+damage	O
+leading	O
+to	O
+decreased	O
+activities	O
+of	O
+oxidative	O
+phosphorylation	O
+complexes	O
+containing	O
+mtDNA	O
+-	O
+encoded	O
+subunits	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+investigated	O
+whether	O
+increased	O
+generation	O
+of	O
+FR	O
+during	O
+status	B-Disease
+epilepticus	I-Disease
+would	O
+be	O
+sufficient	O
+to	O
+provoke	O
+abnormalities	O
+in	O
+mtDNA	O
+and	O
+in	O
+the	O
+expression	O
+and	O
+activity	O
+of	O
+cytochrome	O
+c	O
+oxidase	O
+(	O
+CCO	O
+)	O
+,	O
+complex	O
+IV	O
+of	O
+the	O
+respiratory	O
+chain	O
+,	O
+in	O
+the	O
+chronic	O
+phase	O
+of	O
+the	O
+pilocarpine	B-Chemical
+model	O
+of	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+.	O
+
+DNA	O
+analysis	O
+revealed	O
+low	O
+amounts	O
+of	O
+a	O
+4	O
+.	O
+8	O
+kb	O
+mtDNA	O
+deletion	O
+but	O
+with	O
+no	O
+differences	O
+in	O
+frequency	O
+or	O
+quantity	O
+in	O
+the	O
+control	O
+and	O
+experimental	O
+groups	O
+.	O
+
+We	O
+did	O
+not	O
+find	O
+abnormalities	O
+in	O
+the	O
+expression	O
+and	O
+distribution	O
+of	O
+an	O
+mtDNA	O
+-	O
+encoded	O
+subunit	O
+of	O
+CCO	O
+(	O
+CCO	O
+-	O
+I	O
+)	O
+or	O
+a	O
+relative	O
+decrease	O
+in	O
+CCO	O
+-	O
+I	O
+when	O
+compared	O
+with	O
+nuclear	O
+-	O
+encoded	O
+subunits	O
+(	O
+CCO	O
+-	O
+IV	O
+and	O
+SDH	O
+-	O
+fp	O
+)	O
+.	O
+
+No	O
+abnormality	O
+in	O
+CCO	O
+activity	O
+was	O
+observed	O
+through	O
+histochemistry	O
+.	O
+
+Although	O
+evidences	O
+of	O
+mitochondrial	B-Disease
+abnormalities	I-Disease
+were	O
+found	O
+in	O
+previously	O
+published	O
+studies	O
+,	O
+our	O
+results	O
+do	O
+not	O
+suggest	O
+that	O
+the	O
+FRs	O
+,	O
+generated	O
+during	O
+the	O
+acute	O
+phase	O
+,	O
+determined	O
+important	O
+abnormalities	O
+in	O
+mtDNA	O
+,	O
+in	O
+expression	O
+of	O
+CCO	O
+-	O
+I	O
+,	O
+and	O
+in	O
+CCO	O
+activity	O
+.	O
+
+Adverse	O
+effect	O
+of	O
+the	O
+calcium	B-Chemical
+channel	O
+blocker	O
+nitrendipine	B-Chemical
+on	O
+nephrosclerosis	B-Disease
+in	O
+rats	O
+with	O
+renovascular	B-Disease
+hypertension	I-Disease
+.	O
+
+The	O
+effect	O
+of	O
+a	O
+6	O
+-	O
+week	O
+treatment	O
+with	O
+the	O
+calcium	B-Chemical
+channel	O
+blocker	O
+nitrendipine	B-Chemical
+or	O
+the	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+inhibitor	O
+enalapril	B-Chemical
+on	O
+blood	O
+pressure	O
+,	O
+albuminuria	B-Disease
+,	O
+renal	O
+hemodynamics	O
+,	O
+and	O
+morphology	O
+of	O
+the	O
+nonclipped	O
+kidney	O
+was	O
+studied	O
+in	O
+rats	O
+with	O
+two	O
+-	O
+kidney	O
+,	O
+one	O
+clip	O
+renovascular	B-Disease
+hypertension	I-Disease
+.	O
+
+Six	O
+weeks	O
+after	O
+clipping	O
+of	O
+one	O
+renal	O
+artery	O
+,	O
+hypertensive	B-Disease
+rats	O
+(	O
+178	O
++	O
+/	O
+-	O
+4	O
+mm	O
+Hg	O
+)	O
+were	O
+randomly	O
+assigned	O
+to	O
+three	O
+groups	O
+:	O
+untreated	O
+hypertensive	B-Disease
+controls	O
+(	O
+n	O
+=	O
+8	O
+)	O
+,	O
+enalapril	B-Chemical
+-	O
+treated	O
+(	O
+n	O
+=	O
+8	O
+)	O
+,	O
+or	O
+nitrendipine	B-Chemical
+-	O
+treated	O
+(	O
+n	O
+=	O
+10	O
+)	O
+.	O
+
+Sham	O
+-	O
+operated	O
+rats	O
+served	O
+as	O
+normotensive	O
+controls	O
+(	O
+128	O
++	O
+/	O
+-	O
+3	O
+mm	O
+Hg	O
+,	O
+n	O
+=	O
+8	O
+)	O
+.	O
+
+After	O
+6	O
+weeks	O
+of	O
+treatment	O
+,	O
+renal	O
+hemodynamics	O
+(	O
+glomerular	O
+filtration	O
+rate	O
+and	O
+renal	O
+plasma	O
+flow	O
+)	O
+were	O
+measured	O
+in	O
+the	O
+anesthetized	O
+rats	O
+.	O
+
+Renal	O
+tissue	O
+was	O
+obtained	O
+for	O
+determination	O
+of	O
+glomerular	O
+size	O
+and	O
+sclerosis	O
+.	O
+
+Enalapril	B-Chemical
+but	O
+not	O
+nitrendipine	B-Chemical
+reduced	O
+blood	O
+pressure	O
+significantly	O
+.	O
+
+After	O
+6	O
+weeks	O
+of	O
+therapy	O
+,	O
+glomerular	O
+filtration	O
+rate	O
+was	O
+not	O
+different	O
+among	O
+the	O
+studied	O
+groups	O
+.	O
+
+Renal	O
+plasma	O
+flow	O
+increased	O
+,	O
+but	O
+albumin	O
+excretion	O
+and	O
+glomerulosclerosis	B-Disease
+did	O
+not	O
+change	O
+after	O
+enalapril	B-Chemical
+treatment	O
+.	O
+
+In	O
+contrast	O
+,	O
+in	O
+the	O
+nitrendipine	B-Chemical
+-	O
+treated	O
+group	O
+albuminuria	B-Disease
+increased	O
+from	O
+12	O
+.	O
+8	O
++	O
+/	O
+-	O
+2	O
+progressively	O
+to	O
+163	O
++	O
+/	O
+-	O
+55	O
+compared	O
+with	O
+19	O
+.	O
+2	O
++	O
+/	O
+-	O
+9	O
+mg	O
+/	O
+24	O
+hr	O
+in	O
+the	O
+hypertensive	B-Disease
+controls	O
+.	O
+
+Furthermore	O
+,	O
+glomerulosclerosis	B-Disease
+index	O
+was	O
+significantly	O
+increased	O
+in	O
+the	O
+nitrendipine	B-Chemical
+-	O
+treated	O
+group	O
+compared	O
+with	O
+the	O
+hypertensive	B-Disease
+controls	O
+(	O
+0	O
+.	O
+38	O
++	O
+/	O
+-	O
+0	O
+.	O
+1	O
+versus	O
+0	O
+.	O
+13	O
++	O
+/	O
+-	O
+0	O
+.	O
+04	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+glomerular	O
+size	O
+was	O
+higher	O
+in	O
+the	O
+nitrendipine	B-Chemical
+-	O
+treated	O
+group	O
+(	O
+14	O
+.	O
+9	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+10	O
+(	O
+-	O
+3	O
+)	O
+mm2	O
+)	O
+but	O
+lower	O
+in	O
+the	O
+enalapril	B-Chemical
+-	O
+treated	O
+group	O
+(	O
+11	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+15	O
+10	O
+(	O
+-	O
+3	O
+)	O
+mm2	O
+)	O
+compared	O
+with	O
+the	O
+hypertensive	B-Disease
+controls	O
+(	O
+12	O
+.	O
+1	O
++	O
+/	O
+-	O
+0	O
+.	O
+17	O
+10	O
+(	O
+-	O
+3	O
+)	O
+mm2	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Ketoconazole	B-Chemical
+induced	O
+torsades	B-Disease
+de	I-Disease
+pointes	I-Disease
+without	O
+concomitant	O
+use	O
+of	O
+QT	O
+interval	O
+-	O
+prolonging	O
+drug	O
+.	O
+
+Ketoconazole	B-Chemical
+is	O
+not	O
+known	O
+to	O
+be	O
+proarrhythmic	O
+without	O
+concomitant	O
+use	O
+of	O
+QT	O
+interval	O
+-	O
+prolonging	O
+drugs	O
+.	O
+
+We	O
+report	O
+a	O
+woman	O
+with	O
+coronary	B-Disease
+artery	I-Disease
+disease	I-Disease
+who	O
+developed	O
+a	O
+markedly	O
+prolonged	B-Disease
+QT	I-Disease
+interval	I-Disease
+and	O
+torsades	B-Disease
+de	I-Disease
+pointes	I-Disease
+(	O
+TdP	B-Disease
+)	O
+after	O
+taking	O
+ketoconazole	B-Chemical
+for	O
+treatment	O
+of	O
+fungal	B-Disease
+infection	I-Disease
+.	O
+
+Her	O
+QT	O
+interval	O
+returned	O
+to	O
+normal	O
+upon	O
+withdrawal	O
+of	O
+ketoconazole	B-Chemical
+.	O
+
+Genetic	O
+study	O
+did	O
+not	O
+find	O
+any	O
+mutation	O
+in	O
+her	O
+genes	O
+that	O
+encode	O
+cardiac	O
+IKr	O
+channel	O
+proteins	O
+.	O
+
+We	O
+postulate	O
+that	O
+by	O
+virtue	O
+of	O
+its	O
+direct	O
+blocking	O
+action	O
+on	O
+IKr	O
+,	O
+ketoconazole	B-Chemical
+alone	O
+may	O
+prolong	O
+QT	O
+interval	O
+and	O
+induce	O
+TdP	B-Disease
+.	O
+
+This	O
+calls	O
+for	O
+attention	O
+when	O
+ketoconazole	B-Chemical
+is	O
+administered	O
+to	O
+patients	O
+with	O
+risk	O
+factors	O
+for	O
+acquired	O
+long	B-Disease
+QT	I-Disease
+syndrome	I-Disease
+.	O
+
+Cerebral	B-Disease
+vasculitis	I-Disease
+following	O
+oral	O
+methylphenidate	B-Chemical
+intake	O
+in	O
+an	O
+adult	O
+:	O
+a	O
+case	O
+report	O
+.	O
+
+Methylphenidate	B-Chemical
+is	O
+structurally	O
+and	O
+functionally	O
+similar	O
+to	O
+amphetamine	B-Chemical
+.	O
+
+Cerebral	B-Disease
+vasculitis	I-Disease
+associated	O
+with	O
+amphetamine	B-Disease
+abuse	I-Disease
+is	O
+well	O
+documented	O
+,	O
+and	O
+in	O
+rare	O
+cases	O
+ischaemic	B-Disease
+stroke	I-Disease
+has	O
+been	O
+reported	O
+after	O
+methylphenidate	B-Chemical
+intake	O
+in	O
+children	O
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+63	O
+-	O
+year	O
+-	O
+old	O
+female	O
+who	O
+was	O
+treated	O
+with	O
+methylphenidate	B-Chemical
+due	O
+to	O
+hyperactivity	B-Disease
+and	O
+suffered	O
+from	O
+multiple	O
+ischaemic	B-Disease
+strokes	I-Disease
+.	O
+
+We	O
+consider	O
+drug	O
+-	O
+induced	O
+cerebral	B-Disease
+vasculitis	I-Disease
+as	O
+the	O
+most	O
+likely	O
+cause	O
+of	O
+recurrent	O
+ischaemic	B-Disease
+strokes	I-Disease
+in	O
+the	O
+absence	O
+of	O
+any	O
+pathological	O
+findings	O
+during	O
+the	O
+diagnostic	O
+work	O
+-	O
+up	O
+.	O
+
+We	O
+conclude	O
+that	O
+methylphenidate	B-Chemical
+mediated	O
+vasculitis	B-Disease
+should	O
+be	O
+considered	O
+in	O
+patients	O
+with	O
+neurological	O
+symptoms	O
+and	O
+a	O
+history	O
+of	O
+methylphenidate	B-Chemical
+therapy	O
+.	O
+
+This	O
+potential	O
+side	O
+-	O
+effect	O
+,	O
+though	O
+very	O
+rare	O
+,	O
+represents	O
+one	O
+more	O
+reason	O
+to	O
+be	O
+very	O
+restrictive	O
+in	O
+the	O
+use	O
+of	O
+methylphenidate	B-Chemical
+.	O
+
+MDMA	B-Chemical
+polydrug	O
+users	O
+show	O
+process	O
+-	O
+specific	O
+central	O
+executive	O
+impairments	O
+coupled	O
+with	O
+impaired	B-Disease
+social	I-Disease
+and	I-Disease
+emotional	I-Disease
+judgement	I-Disease
+processes	I-Disease
+.	O
+
+In	O
+recent	O
+years	O
+working	O
+memory	B-Disease
+deficits	I-Disease
+have	O
+been	O
+reported	O
+in	O
+users	O
+of	O
+MDMA	B-Chemical
+(	O
+3	B-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+methylenedioxymethamphetamine	I-Chemical
+,	O
+ecstasy	B-Chemical
+)	O
+.	O
+
+The	O
+current	O
+study	O
+aimed	O
+to	O
+assess	O
+the	O
+impact	O
+of	O
+MDMA	B-Chemical
+use	O
+on	O
+three	O
+separate	O
+central	O
+executive	O
+processes	O
+(	O
+set	O
+shifting	O
+,	O
+inhibition	O
+and	O
+memory	O
+updating	O
+)	O
+and	O
+also	O
+on	O
+"	O
+prefrontal	O
+"	O
+mediated	O
+social	O
+and	O
+emotional	O
+judgement	O
+processes	O
+.	O
+
+Fifteen	O
+polydrug	O
+ecstasy	B-Chemical
+users	O
+and	O
+15	O
+polydrug	O
+non	O
+-	O
+ecstasy	B-Chemical
+user	O
+controls	O
+completed	O
+a	O
+general	O
+drug	O
+use	O
+questionnaire	O
+,	O
+the	O
+Brixton	O
+Spatial	O
+Anticipation	O
+task	O
+(	O
+set	O
+shifting	O
+)	O
+,	O
+Backward	O
+Digit	O
+Span	O
+procedure	O
+(	O
+memory	O
+updating	O
+)	O
+,	O
+Inhibition	O
+of	O
+Return	O
+(	O
+inhibition	O
+)	O
+,	O
+an	O
+emotional	O
+intelligence	O
+scale	O
+,	O
+the	O
+Tromso	O
+Social	O
+Intelligence	O
+Scale	O
+and	O
+the	O
+Dysexecutive	O
+Questionnaire	O
+(	O
+DEX	O
+)	O
+.	O
+
+Compared	O
+with	O
+MDMA	B-Chemical
+-	O
+free	O
+polydrug	O
+controls	O
+,	O
+MDMA	B-Chemical
+polydrug	O
+users	O
+showed	O
+impairments	O
+in	O
+set	O
+shifting	O
+and	O
+memory	O
+updating	O
+,	O
+and	O
+also	O
+in	O
+social	O
+and	O
+emotional	O
+judgement	O
+processes	O
+.	O
+
+The	O
+latter	O
+two	O
+deficits	O
+remained	O
+significant	O
+after	O
+controlling	O
+for	O
+other	O
+drug	O
+use	O
+.	O
+
+These	O
+data	O
+lend	O
+further	O
+support	O
+to	O
+the	O
+proposal	O
+that	O
+cognitive	O
+processes	O
+mediated	O
+by	O
+the	O
+prefrontal	O
+cortex	O
+may	O
+be	O
+impaired	O
+by	O
+recreational	O
+ecstasy	B-Chemical
+use	O
+.	O
+
+Phase	O
+II	O
+study	O
+of	O
+the	O
+amsacrine	B-Chemical
+analogue	O
+CI	B-Chemical
+-	I-Chemical
+921	I-Chemical
+(	O
+NSC	B-Chemical
+343499	I-Chemical
+)	O
+in	O
+non	B-Disease
+-	I-Disease
+small	I-Disease
+cell	I-Disease
+lung	I-Disease
+cancer	I-Disease
+.	O
+
+CI	B-Chemical
+-	I-Chemical
+921	I-Chemical
+(	O
+NSC	B-Chemical
+343499	I-Chemical
+;	O
+9	B-Chemical
+-	I-Chemical
+[	I-Chemical
+[	I-Chemical
+2	I-Chemical
+-	I-Chemical
+methoxy	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+[	I-Chemical
+(	I-Chemical
+methylsulphonyl	I-Chemical
+)	I-Chemical
+amino	I-Chemical
+]	I-Chemical
+phenyl	I-Chemical
+]	I-Chemical
+amino	I-Chemical
+]	I-Chemical
+-	I-Chemical
+N	I-Chemical
+,	I-Chemical
+5	I-Chemical
+-	I-Chemical
+dimethyl	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+acridinecarboxamide	I-Chemical
+)	O
+is	O
+a	O
+topoisomerase	O
+II	O
+poison	O
+with	O
+high	O
+experimental	O
+antitumour	O
+activity	O
+.	O
+
+It	O
+was	O
+administered	O
+by	O
+15	O
+min	O
+infusion	O
+to	O
+16	O
+evaluable	O
+patients	O
+with	O
+non	B-Disease
+-	I-Disease
+small	I-Disease
+cell	I-Disease
+lung	I-Disease
+cancer	I-Disease
+(	O
+NSCLC	B-Disease
+)	O
+(	O
+7	O
+with	O
+no	O
+prior	O
+treatment	O
+,	O
+9	O
+patients	O
+in	O
+relapse	O
+following	O
+surgery	O
+/	O
+radiotherapy	O
+)	O
+at	O
+a	O
+dose	O
+(	O
+648	O
+mg	O
+/	O
+m2	O
+divided	O
+over	O
+3	O
+days	O
+,	O
+repeated	O
+every	O
+3	O
+weeks	O
+)	O
+determined	O
+by	O
+phase	O
+I	O
+trial	O
+.	O
+
+Patients	O
+had	O
+a	O
+median	O
+performance	O
+status	O
+of	O
+1	O
+(	O
+WHO	O
+)	O
+,	O
+and	O
+median	O
+age	O
+of	O
+61	O
+years	O
+.	O
+
+The	O
+histology	O
+comprised	O
+squamous	B-Disease
+carcinoma	I-Disease
+(	O
+11	O
+)	O
+,	O
+adenocarcinoma	B-Disease
+(	O
+1	O
+)	O
+,	O
+mixed	O
+histology	O
+(	O
+2	O
+)	O
+,	O
+bronchio	B-Disease
+-	I-Disease
+alveolar	I-Disease
+carcinoma	I-Disease
+(	O
+1	O
+)	O
+and	O
+large	O
+cell	O
+undifferentiated	B-Disease
+carcinoma	I-Disease
+(	O
+1	O
+)	O
+.	O
+
+Neutropenia	B-Disease
+grade	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+3	O
+was	O
+seen	O
+in	O
+15	O
+patients	O
+,	O
+infections	B-Disease
+with	O
+recovery	O
+in	O
+3	O
+,	O
+and	O
+grand	O
+mal	O
+seizures	B-Disease
+in	O
+1	O
+patient	O
+.	O
+
+Grade	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+2	O
+nausea	B-Disease
+and	O
+vomiting	B-Disease
+occurred	O
+in	O
+66	O
+%	O
+courses	O
+and	O
+phlebitis	B-Disease
+in	O
+the	O
+infusion	O
+arm	O
+in	O
+37	O
+%	O
+.	O
+
+1	O
+patient	O
+with	O
+squamous	B-Disease
+cell	I-Disease
+carcinoma	I-Disease
+achieved	O
+a	O
+partial	O
+response	O
+lasting	O
+5	O
+months	O
+.	O
+
+Further	O
+testing	O
+in	O
+this	O
+and	O
+other	O
+tumour	B-Disease
+types	O
+using	O
+multiple	O
+daily	O
+schedules	O
+is	O
+warranted	O
+.	O
+
+Pharmacokinetics	O
+of	O
+desipramine	B-Chemical
+HCl	I-Chemical
+when	O
+administered	O
+with	O
+cinacalcet	B-Chemical
+HCl	I-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+In	O
+vitro	O
+work	O
+has	O
+demonstrated	O
+that	O
+cinacalcet	B-Chemical
+is	O
+a	O
+strong	O
+inhibitor	O
+of	O
+cytochrome	O
+P450	O
+isoenzyme	O
+(	O
+CYP	O
+)	O
+2D6	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+the	O
+effect	O
+of	O
+cinacalcet	B-Chemical
+on	O
+CYP2D6	O
+activity	O
+,	O
+using	O
+desipramine	B-Chemical
+as	O
+a	O
+probe	O
+substrate	O
+,	O
+in	O
+healthy	O
+subjects	O
+.	O
+
+METHODS	O
+:	O
+Seventeen	O
+subjects	O
+who	O
+were	O
+genotyped	O
+as	O
+CYP2D6	O
+extensive	O
+metabolizers	O
+were	O
+enrolled	O
+in	O
+this	O
+randomized	O
+,	O
+open	O
+-	O
+label	O
+,	O
+crossover	O
+study	O
+to	O
+receive	O
+a	O
+single	O
+oral	O
+dose	O
+of	O
+desipramine	B-Chemical
+(	O
+50	O
+mg	O
+)	O
+on	O
+two	O
+separate	O
+occasions	O
+,	O
+once	O
+alone	O
+and	O
+once	O
+after	O
+multiple	O
+doses	O
+of	O
+cinacalcet	B-Chemical
+(	O
+90	O
+mg	O
+for	O
+7	O
+days	O
+)	O
+.	O
+
+Blood	O
+samples	O
+were	O
+obtained	O
+predose	O
+and	O
+up	O
+to	O
+72	O
+h	O
+postdose	O
+.	O
+
+RESULTS	O
+:	O
+Fourteen	O
+subjects	O
+completed	O
+both	O
+treatment	O
+arms	O
+.	O
+
+Relative	O
+to	O
+desipramine	B-Chemical
+alone	O
+,	O
+mean	O
+AUC	O
+and	O
+C	O
+(	O
+max	O
+)	O
+of	O
+desipramine	B-Chemical
+increased	O
+3	O
+.	O
+6	O
+-	O
+and	O
+1	O
+.	O
+8	O
+-	O
+fold	O
+when	O
+coadministered	O
+with	O
+cinacalcet	B-Chemical
+.	O
+
+The	O
+t	O
+(	O
+1	O
+/	O
+2	O
+,	O
+z	O
+)	O
+of	O
+desipramine	B-Chemical
+was	O
+longer	O
+when	O
+desipramine	B-Chemical
+was	O
+coadministered	O
+with	O
+cinacalcet	B-Chemical
+(	O
+21	O
+.	O
+0	O
+versus	O
+43	O
+.	O
+3	O
+hs	O
+)	O
+.	O
+
+The	O
+t	O
+(	O
+max	O
+)	O
+was	O
+similar	O
+between	O
+the	O
+regimens	O
+.	O
+
+Fewer	O
+subjects	O
+reported	O
+adverse	O
+events	O
+following	O
+treatment	O
+with	O
+desipramine	B-Chemical
+alone	O
+than	O
+when	O
+receiving	O
+desipramine	B-Chemical
+with	O
+cinacalcet	B-Chemical
+(	O
+33	O
+versus	O
+86	O
+%	O
+)	O
+,	O
+the	O
+most	O
+frequent	O
+of	O
+which	O
+(	O
+nausea	B-Disease
+and	O
+headache	B-Disease
+)	O
+have	O
+been	O
+reported	O
+for	O
+patients	O
+treated	O
+with	O
+either	O
+desipramine	B-Chemical
+or	O
+cinacalcet	B-Chemical
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+study	O
+demonstrates	O
+that	O
+cinacalcet	B-Chemical
+is	O
+a	O
+strong	O
+inhibitor	O
+of	O
+CYP2D6	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+during	O
+concomitant	O
+treatment	O
+with	O
+cinacalcet	B-Chemical
+,	O
+dose	O
+adjustment	O
+may	O
+be	O
+necessary	O
+for	O
+drugs	O
+that	O
+demonstrate	O
+a	O
+narrow	O
+therapeutic	O
+index	O
+and	O
+are	O
+metabolized	O
+by	O
+CYP2D6	O
+.	O
+
+Case	O
+report	O
+:	O
+acute	O
+unintentional	O
+carbachol	B-Chemical
+intoxication	O
+.	O
+
+INTRODUCTION	O
+:	O
+Intoxications	O
+with	O
+carbachol	B-Chemical
+,	O
+a	O
+muscarinic	O
+cholinergic	O
+receptor	O
+agonist	O
+are	O
+rare	O
+.	O
+
+We	O
+report	O
+an	O
+interesting	O
+case	O
+investigating	O
+a	O
+(	O
+near	O
+)	O
+fatal	O
+poisoning	B-Disease
+.	O
+
+METHODS	O
+:	O
+The	O
+son	O
+of	O
+an	O
+84	O
+-	O
+year	O
+-	O
+old	O
+male	O
+discovered	O
+a	O
+newspaper	O
+report	O
+stating	O
+clinical	O
+success	O
+with	O
+plant	O
+extracts	O
+in	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+The	O
+mode	O
+of	O
+action	O
+was	O
+said	O
+to	O
+be	O
+comparable	O
+to	O
+that	O
+of	O
+the	O
+synthetic	O
+compound	O
+'	O
+carbamylcholin	B-Chemical
+'	O
+;	O
+that	O
+is	O
+,	O
+carbachol	B-Chemical
+.	O
+
+He	O
+bought	O
+25	O
+g	O
+of	O
+carbachol	B-Chemical
+as	O
+pure	O
+substance	O
+in	O
+a	O
+pharmacy	O
+,	O
+and	O
+the	O
+father	O
+was	O
+administered	O
+400	O
+to	O
+500	O
+mg	O
+.	O
+
+Carbachol	B-Chemical
+concentrations	O
+in	O
+serum	O
+and	O
+urine	O
+on	O
+day	O
+1	O
+and	O
+2	O
+of	O
+hospital	O
+admission	O
+were	O
+analysed	O
+by	O
+HPLC	O
+-	O
+mass	O
+spectrometry	O
+.	O
+
+RESULTS	O
+:	O
+Minutes	O
+after	O
+oral	O
+administration	O
+,	O
+the	O
+patient	O
+developed	O
+nausea	B-Disease
+,	O
+sweating	O
+and	O
+hypotension	B-Disease
+,	O
+and	O
+finally	O
+collapsed	O
+.	O
+
+Bradycardia	B-Disease
+,	O
+cholinergic	O
+symptoms	O
+and	O
+asystole	B-Disease
+occurred	O
+.	O
+
+Initial	O
+cardiopulmonary	O
+resuscitation	O
+and	O
+immediate	O
+treatment	O
+with	O
+adrenaline	B-Chemical
+(	O
+epinephrine	B-Chemical
+)	O
+,	O
+atropine	B-Chemical
+and	O
+furosemide	B-Chemical
+was	O
+successful	O
+.	O
+
+On	O
+hospital	O
+admission	O
+,	O
+blood	O
+pressure	O
+of	O
+the	O
+intubated	O
+,	O
+bradyarrhythmic	O
+patient	O
+was	O
+100	O
+/	O
+65	O
+mmHg	O
+.	O
+
+Further	O
+signs	O
+were	O
+hyperhidrosis	B-Disease
+,	O
+hypersalivation	B-Disease
+,	O
+bronchorrhoea	B-Disease
+,	O
+and	O
+severe	O
+miosis	B-Disease
+;	O
+the	O
+electrocardiographic	O
+finding	O
+was	O
+atrio	B-Disease
+-	I-Disease
+ventricular	I-Disease
+dissociation	I-Disease
+.	O
+
+High	O
+doses	O
+of	O
+atropine	B-Chemical
+(	O
+up	O
+to	O
+50	O
+mg	O
+per	O
+24	O
+hours	O
+)	O
+,	O
+adrenaline	B-Chemical
+and	O
+dopamine	B-Chemical
+were	O
+necessary	O
+.	O
+
+The	O
+patient	O
+was	O
+extubated	O
+1	O
+week	O
+later	O
+.	O
+
+However	O
+,	O
+increased	O
+dyspnoea	B-Disease
+and	O
+bronchospasm	B-Disease
+necessitated	O
+reintubation	O
+.	O
+
+Respiratory	B-Disease
+insufficiency	I-Disease
+was	O
+further	O
+worsened	O
+by	O
+Proteus	B-Disease
+mirabilis	I-Disease
+infection	I-Disease
+and	O
+severe	O
+bronchoconstriction	O
+.	O
+
+One	O
+week	O
+later	O
+,	O
+the	O
+patient	O
+was	O
+again	O
+extubated	O
+and	O
+3	O
+days	O
+later	O
+was	O
+transferred	O
+to	O
+a	O
+peripheral	O
+ward	O
+.	O
+
+On	O
+the	O
+next	O
+day	O
+he	O
+died	O
+,	O
+probably	O
+as	O
+a	O
+result	O
+of	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+Serum	O
+samples	O
+from	O
+the	O
+first	O
+and	O
+second	O
+days	O
+contained	O
+3	O
+.	O
+6	O
+and	O
+1	O
+.	O
+9	O
+mg	O
+/	O
+l	O
+carbachol	B-Chemical
+,	O
+respectively	O
+.	O
+
+The	O
+corresponding	O
+urine	O
+concentrations	O
+amounted	O
+to	O
+374	O
+and	O
+554	O
+mg	O
+/	O
+l	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+case	O
+started	O
+with	O
+a	O
+media	O
+report	O
+in	O
+a	O
+popular	O
+newspaper	O
+,	O
+initiated	O
+by	O
+published	O
+,	O
+peer	O
+-	O
+reviewed	O
+research	O
+on	O
+herbals	O
+,	O
+and	O
+involved	O
+human	O
+failure	O
+in	O
+a	O
+case	O
+history	O
+,	O
+medical	O
+examination	O
+and	O
+clinical	O
+treatment	O
+.	O
+
+For	O
+the	O
+first	O
+time	O
+,	O
+an	O
+analytical	O
+method	O
+for	O
+the	O
+determination	O
+of	O
+carbachol	B-Chemical
+in	O
+plasma	O
+and	O
+urine	O
+has	O
+been	O
+developed	O
+.	O
+
+The	O
+analysed	O
+carbachol	B-Chemical
+concentration	O
+exceeded	O
+the	O
+supposed	O
+serum	O
+level	O
+resulting	O
+from	O
+a	O
+therapeutic	O
+dose	O
+by	O
+a	O
+factor	O
+of	O
+130	O
+to	O
+260	O
+.	O
+
+Especially	O
+in	O
+old	O
+patients	O
+,	O
+intensivists	O
+should	O
+consider	O
+intoxications	O
+(	O
+with	O
+cholinergics	O
+)	O
+as	O
+a	O
+cause	O
+of	O
+acute	B-Disease
+cardiovascular	I-Disease
+failure	I-Disease
+.	O
+
+Pharmacological	O
+evidence	O
+for	O
+the	O
+potential	O
+of	O
+Daucus	O
+carota	O
+in	O
+the	O
+management	O
+of	O
+cognitive	B-Disease
+dysfunctions	I-Disease
+.	O
+
+The	O
+present	O
+study	O
+was	O
+aimed	O
+at	O
+investigating	O
+the	O
+effects	O
+of	O
+Daucus	O
+carota	O
+seeds	O
+on	O
+cognitive	O
+functions	O
+,	O
+total	O
+serum	O
+cholesterol	B-Chemical
+levels	O
+and	O
+brain	O
+cholinesterase	O
+activity	O
+in	O
+mice	O
+.	O
+
+The	O
+ethanolic	O
+extract	B-Chemical
+of	I-Chemical
+Daucus	I-Chemical
+carota	I-Chemical
+seeds	I-Chemical
+(	O
+DCE	B-Chemical
+)	O
+was	O
+administered	O
+orally	O
+in	O
+three	O
+doses	O
+(	O
+100	O
+,	O
+200	O
+,	O
+400	O
+mg	O
+/	O
+kg	O
+)	O
+for	O
+seven	O
+successive	O
+days	O
+to	O
+different	O
+groups	O
+of	O
+young	O
+and	O
+aged	O
+mice	O
+.	O
+
+Elevated	O
+plus	O
+maze	O
+and	O
+passive	O
+avoidance	O
+apparatus	O
+served	O
+as	O
+the	O
+exteroceptive	O
+behavioral	O
+models	O
+for	O
+testing	O
+memory	O
+.	O
+
+Diazepam	B-Chemical
+-	O
+,	O
+scopolamine	B-Chemical
+-	O
+and	O
+ageing	O
+-	O
+induced	O
+amnesia	B-Disease
+served	O
+as	O
+the	O
+interoceptive	O
+behavioral	O
+models	O
+.	O
+
+DCE	B-Chemical
+(	O
+200	O
+,	O
+400	O
+mg	O
+/	O
+kg	O
+,	O
+p	O
+.	O
+o	O
+.	O
+)	O
+showed	O
+significant	O
+improvement	O
+in	O
+memory	O
+scores	O
+of	O
+young	O
+and	O
+aged	O
+mice	O
+.	O
+
+The	O
+extent	O
+of	O
+memory	O
+improvement	O
+evoked	O
+by	O
+DCE	B-Chemical
+was	O
+23	O
+%	O
+at	O
+the	O
+dose	O
+of	O
+200	O
+mg	O
+/	O
+kg	O
+and	O
+35	O
+%	O
+at	O
+the	O
+dose	O
+of	O
+400	O
+mg	O
+/	O
+kg	O
+in	O
+young	O
+mice	O
+using	O
+elevated	O
+plus	O
+maze	O
+.	O
+
+Similarly	O
+,	O
+significant	O
+improvements	O
+in	O
+memory	O
+scores	O
+were	O
+observed	O
+using	O
+passive	O
+avoidance	O
+apparatus	O
+and	O
+aged	O
+mice	O
+.	O
+
+Furthermore	O
+,	O
+DCE	B-Chemical
+reversed	O
+the	O
+amnesia	B-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+(	O
+0	O
+.	O
+4	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+and	O
+diazepam	B-Chemical
+(	O
+1	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+.	O
+
+Daucus	B-Chemical
+carota	I-Chemical
+extract	I-Chemical
+(	O
+200	O
+,	O
+400	O
+mg	O
+/	O
+kg	O
+,	O
+p	O
+.	O
+o	O
+.	O
+)	O
+reduced	O
+significantly	O
+the	O
+brain	O
+acetylcholinesterase	O
+activity	O
+and	O
+cholesterol	B-Chemical
+levels	O
+in	O
+young	O
+and	O
+aged	O
+mice	O
+.	O
+
+The	O
+extent	O
+of	O
+inhibition	O
+of	O
+brain	O
+cholinesterase	O
+activity	O
+evoked	O
+by	O
+DCE	B-Chemical
+at	O
+the	O
+dose	O
+of	O
+400	O
+mg	O
+/	O
+kg	O
+was	O
+22	O
+%	O
+in	O
+young	O
+and	O
+19	O
+%	O
+in	O
+aged	O
+mice	O
+.	O
+
+There	O
+was	O
+a	O
+remarkable	O
+reduction	O
+in	O
+total	O
+cholesterol	B-Chemical
+level	O
+as	O
+well	O
+,	O
+to	O
+the	O
+extent	O
+of	O
+23	O
+%	O
+in	O
+young	O
+and	O
+21	O
+%	O
+in	O
+aged	O
+animals	O
+with	O
+this	O
+dose	O
+of	O
+DCE	B-Chemical
+.	O
+
+Therefore	O
+,	O
+DCE	B-Chemical
+may	O
+prove	O
+to	O
+be	O
+a	O
+useful	O
+remedy	O
+for	O
+the	O
+management	O
+of	O
+cognitive	B-Disease
+dysfunctions	I-Disease
+on	O
+account	O
+of	O
+its	O
+multifarious	O
+beneficial	O
+effects	O
+such	O
+as	O
+,	O
+memory	O
+improving	O
+property	O
+,	O
+cholesterol	B-Chemical
+lowering	O
+property	O
+and	O
+anticholinesterase	O
+activity	O
+.	O
+
+Valproic	B-Chemical
+acid	I-Chemical
+induced	O
+encephalopathy	B-Disease
+-	O
+-	O
+19	O
+new	O
+cases	O
+in	O
+Germany	O
+from	O
+1994	O
+to	O
+2003	O
+-	O
+-	O
+a	O
+side	O
+effect	O
+associated	O
+to	O
+VPA	B-Chemical
+-	O
+therapy	O
+not	O
+only	O
+in	O
+young	O
+children	O
+.	O
+
+Valproic	B-Chemical
+acid	I-Chemical
+(	O
+VPA	B-Chemical
+)	O
+is	O
+a	O
+broad	O
+-	O
+spectrum	O
+antiepileptic	O
+drug	O
+and	O
+is	O
+usually	O
+well	O
+-	O
+tolerated	O
+.	O
+
+Rare	O
+serious	O
+complications	O
+may	O
+occur	O
+in	O
+some	O
+patients	O
+,	O
+including	O
+haemorrhagic	O
+pancreatitis	B-Disease
+,	O
+bone	B-Disease
+marrow	I-Disease
+suppression	I-Disease
+,	O
+VPA	B-Chemical
+-	O
+induced	O
+hepatotoxicity	B-Disease
+and	O
+VPA	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+.	O
+
+The	O
+typical	O
+signs	O
+of	O
+VPA	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+are	O
+impaired	B-Disease
+consciousness	I-Disease
+,	O
+sometimes	O
+marked	O
+EEG	O
+background	O
+slowing	O
+,	O
+increased	O
+seizure	B-Disease
+frequency	O
+,	O
+with	O
+or	O
+without	O
+hyperammonemia	B-Disease
+.	O
+
+There	O
+is	O
+still	O
+no	O
+proof	O
+of	O
+causative	O
+effect	O
+of	O
+VPA	B-Chemical
+in	O
+patients	O
+with	O
+encephalopathy	B-Disease
+,	O
+but	O
+only	O
+of	O
+an	O
+association	O
+with	O
+an	O
+assumed	O
+causal	O
+relation	O
+.	O
+
+We	O
+report	O
+19	O
+patients	O
+with	O
+VPA	B-Chemical
+-	O
+associated	O
+encephalopathy	B-Disease
+in	O
+Germany	O
+from	O
+the	O
+years	O
+1994	O
+to	O
+2003	O
+,	O
+none	O
+of	O
+whom	O
+had	O
+been	O
+published	O
+previously	O
+.	O
+
+Cerebral	B-Disease
+haemorrhage	I-Disease
+induced	O
+by	O
+warfarin	B-Chemical
+-	O
+the	O
+influence	O
+of	O
+drug	O
+-	O
+drug	O
+interactions	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+evaluate	O
+the	O
+frequency	O
+,	O
+severity	O
+and	O
+preventability	O
+of	O
+warfarin	B-Chemical
+-	O
+induced	O
+cerebral	B-Disease
+haemorrhages	I-Disease
+due	O
+to	O
+warfarin	B-Chemical
+and	O
+warfarin	B-Chemical
+-	O
+drug	O
+interactions	O
+in	O
+patients	O
+living	O
+in	O
+the	O
+county	O
+of	O
+Osterg	O
+tland	O
+,	O
+Sweden	O
+.	O
+
+METHODS	O
+:	O
+All	O
+patients	O
+with	O
+a	O
+diagnosed	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+at	O
+three	O
+hospitals	O
+during	O
+the	O
+period	O
+2000	O
+-	O
+2002	O
+were	O
+identified	O
+.	O
+
+Medical	O
+records	O
+were	O
+studied	O
+retrospectively	O
+to	O
+evaluate	O
+whether	O
+warfarin	B-Chemical
+and	O
+warfarin	B-Chemical
+-	O
+drug	O
+interactions	O
+could	O
+have	O
+caused	O
+the	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+.	O
+
+The	O
+proportion	O
+of	O
+possibly	O
+avoidable	O
+cases	O
+due	O
+to	O
+drug	O
+interactions	O
+was	O
+estimated	O
+.	O
+
+RESULTS	O
+:	O
+Among	O
+593	O
+patients	O
+with	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+,	O
+59	O
+(	O
+10	O
+%	O
+)	O
+were	O
+assessed	O
+as	O
+related	O
+to	O
+warfarin	B-Chemical
+treatment	O
+.	O
+
+This	O
+imply	O
+an	O
+incidence	O
+of	O
+1	O
+.	O
+7	O
+/	O
+100	O
+,	O
+000	O
+treatment	O
+years	O
+.	O
+
+Of	O
+the	O
+59	O
+cases	O
+,	O
+26	O
+(	O
+44	O
+%	O
+)	O
+had	O
+a	O
+fatal	O
+outcome	O
+,	O
+compared	O
+to	O
+136	O
+(	O
+25	O
+%	O
+)	O
+among	O
+the	O
+non	O
+-	O
+warfarin	B-Chemical
+patients	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+A	O
+warfarin	B-Chemical
+-	O
+drug	O
+interaction	O
+could	O
+have	O
+contributed	O
+to	O
+the	O
+haemorrhage	B-Disease
+in	O
+24	O
+(	O
+41	O
+%	O
+)	O
+of	O
+the	O
+warfarin	B-Chemical
+patients	O
+and	O
+in	O
+7	O
+of	O
+these	O
+(	O
+12	O
+%	O
+)	O
+the	O
+bleeding	B-Disease
+complication	O
+was	O
+considered	O
+being	O
+possible	O
+to	O
+avoid	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Warfarin	B-Chemical
+-	O
+induced	O
+cerebral	B-Disease
+haemorrhages	I-Disease
+are	O
+a	O
+major	O
+clinical	O
+problem	O
+with	O
+a	O
+high	O
+fatality	O
+rate	O
+.	O
+
+Almost	O
+half	O
+of	O
+the	O
+cases	O
+was	O
+related	O
+to	O
+a	O
+warfarin	B-Chemical
+-	O
+drug	O
+interaction	O
+.	O
+
+A	O
+significant	O
+proportion	O
+of	O
+warfarin	B-Chemical
+-	O
+related	O
+cerebral	B-Disease
+haemorrhages	I-Disease
+might	O
+have	O
+been	O
+prevented	O
+if	O
+greater	O
+caution	O
+had	O
+been	O
+taken	O
+when	O
+prescribing	O
+drugs	O
+known	O
+to	O
+interact	O
+with	O
+warfarin	B-Chemical
+.	O
+
+Antipsychotic	O
+-	O
+like	O
+profile	O
+of	O
+thioperamide	B-Chemical
+,	O
+a	O
+selective	O
+H3	O
+-	O
+receptor	O
+antagonist	O
+in	O
+mice	O
+.	O
+
+Experimental	O
+and	O
+clinical	O
+evidence	O
+points	O
+to	O
+a	O
+role	O
+of	O
+central	O
+histaminergic	O
+system	O
+in	O
+the	O
+pathogenesis	O
+of	O
+schizophrenia	B-Disease
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+study	O
+the	O
+effect	O
+of	O
+histamine	B-Chemical
+H	O
+(	O
+3	O
+)	O
+-	O
+receptor	O
+ligands	O
+on	O
+neuroleptic	O
+-	O
+induced	O
+catalepsy	B-Disease
+,	O
+apomorphine	B-Chemical
+-	O
+induced	O
+climbing	O
+behavior	O
+and	O
+amphetamine	B-Chemical
+-	O
+induced	O
+locomotor	O
+activities	O
+in	O
+mice	O
+.	O
+
+Catalepsy	B-Disease
+was	O
+induced	O
+by	O
+haloperidol	B-Chemical
+(	O
+2	O
+mg	O
+/	O
+kg	O
+p	O
+.	O
+o	O
+.	O
+)	O
+,	O
+while	O
+apomorphine	B-Chemical
+(	O
+1	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+)	O
+and	O
+amphetamine	B-Chemical
+(	O
+2	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+)	O
+were	O
+used	O
+for	O
+studying	O
+climbing	O
+behavior	O
+and	O
+locomotor	O
+activities	O
+,	O
+respectively	O
+.	O
+
+(	B-Chemical
+R	I-Chemical
+)	I-Chemical
+-	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+methylhistamine	I-Chemical
+(	O
+RAMH	B-Chemical
+)	O
+(	O
+5	O
+microg	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+)	O
+and	O
+thioperamide	B-Chemical
+(	O
+THP	B-Chemical
+)	O
+(	O
+15	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+,	O
+per	O
+se	O
+did	O
+not	O
+cause	O
+catalepsy	B-Disease
+.	O
+
+Administration	O
+of	O
+THP	B-Chemical
+(	O
+3	O
+.	O
+75	O
+,	O
+7	O
+.	O
+5	O
+and	O
+15	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+1	O
+h	O
+prior	O
+to	O
+haloperidol	B-Chemical
+resulted	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+increase	O
+in	O
+the	O
+catalepsy	B-Disease
+times	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+However	O
+,	O
+pretreatment	O
+with	O
+RAMH	B-Chemical
+significantly	O
+reversed	O
+such	O
+an	O
+effect	O
+of	O
+THP	B-Chemical
+(	O
+15	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+.	O
+
+RAMH	B-Chemical
+per	O
+se	O
+showed	O
+significant	O
+reduction	O
+in	O
+locomotor	O
+time	O
+,	O
+distance	O
+traveled	O
+and	O
+average	O
+speed	O
+but	O
+THP	B-Chemical
+(	O
+15	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+per	O
+se	O
+had	O
+no	O
+effect	O
+on	O
+these	O
+parameters	O
+.	O
+
+On	O
+amphetamine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+,	O
+THP	B-Chemical
+(	O
+3	O
+.	O
+75	O
+and	O
+7	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+reduced	O
+locomotor	O
+time	O
+,	O
+distance	O
+traveled	O
+and	O
+average	O
+speed	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Pretreatment	O
+with	O
+RAMH	B-Chemical
+(	O
+5	O
+microg	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+)	O
+could	O
+partially	O
+reverse	O
+such	O
+effects	O
+of	O
+THP	B-Chemical
+(	O
+3	O
+.	O
+75	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+.	O
+
+Climbing	O
+behavior	O
+induced	O
+by	O
+apomorphine	B-Chemical
+was	O
+reduced	O
+in	O
+animals	O
+treated	O
+with	O
+THP	B-Chemical
+.	O
+
+Such	O
+an	O
+effect	O
+was	O
+,	O
+however	O
+,	O
+reversed	O
+in	O
+presence	O
+of	O
+RAMH	B-Chemical
+.	O
+
+THP	B-Chemical
+exhibited	O
+an	O
+antipsychotic	O
+-	O
+like	O
+profile	O
+by	O
+potentiating	O
+haloperidol	B-Chemical
+-	O
+induced	O
+catalepsy	B-Disease
+,	O
+reducing	O
+amphetamine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+and	O
+reducing	O
+apomorphine	B-Chemical
+-	O
+induced	O
+climbing	O
+in	O
+mice	O
+.	O
+
+Such	O
+effects	O
+of	O
+THP	B-Chemical
+were	O
+reversed	O
+by	O
+RAMH	B-Chemical
+indicating	O
+the	O
+involvement	O
+of	O
+histamine	B-Chemical
+H	O
+(	O
+3	O
+)	O
+-	O
+receptors	O
+.	O
+
+Findings	O
+suggest	O
+a	O
+potential	O
+for	O
+H	O
+(	O
+3	O
+)	O
+-	O
+receptor	O
+antagonists	O
+in	O
+improving	O
+the	O
+refractory	O
+cases	O
+of	O
+schizophrenia	B-Disease
+.	O
+
+Cauda	B-Disease
+equina	I-Disease
+syndrome	I-Disease
+after	O
+epidural	O
+steroid	B-Chemical
+injection	O
+:	O
+a	O
+case	O
+report	O
+.	O
+
+OBJECTIVE	O
+:	O
+Conventional	O
+treatment	O
+methods	O
+of	O
+lumbusacral	O
+radiculopathy	B-Disease
+are	O
+physical	O
+therapy	O
+,	O
+epidural	O
+steroid	B-Chemical
+injections	O
+,	O
+oral	O
+medications	O
+,	O
+and	O
+spinal	O
+manipulative	O
+therapy	O
+.	O
+
+Cauda	B-Disease
+equina	I-Disease
+syndrome	I-Disease
+is	O
+a	O
+rare	O
+complication	O
+of	O
+epidural	O
+anesthesia	O
+.	O
+
+The	O
+following	O
+case	O
+is	O
+a	O
+report	O
+of	O
+cauda	B-Disease
+equina	I-Disease
+syndrome	I-Disease
+possibly	O
+caused	O
+by	O
+epidural	O
+injection	O
+of	O
+triamcinolone	B-Chemical
+and	O
+bupivacaine	B-Chemical
+.	O
+
+CLINICAL	O
+FEATURES	O
+:	O
+A	O
+50	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+low	B-Disease
+back	I-Disease
+and	I-Disease
+right	I-Disease
+leg	I-Disease
+pain	I-Disease
+was	O
+scheduled	O
+for	O
+epidural	O
+steroid	B-Chemical
+injection	O
+.	O
+
+INTERVENTION	O
+AND	O
+OUTCOME	O
+:	O
+An	O
+18	O
+-	O
+gauge	O
+Touhy	O
+needle	O
+was	O
+inserted	O
+until	O
+loss	O
+of	O
+resistance	O
+occurred	O
+at	O
+the	O
+L4	O
+-	O
+5	O
+level	O
+.	O
+
+Spread	O
+of	O
+the	O
+contrast	O
+medium	O
+within	O
+the	O
+epidural	O
+space	O
+was	O
+determined	O
+by	O
+radiographic	O
+imaging	O
+.	O
+
+After	O
+verifying	O
+the	O
+epidural	O
+space	O
+,	O
+bupivacaine	B-Chemical
+and	O
+triamcinolone	B-Chemical
+diacetate	I-Chemical
+were	O
+injected	O
+.	O
+
+After	O
+the	O
+injection	O
+,	O
+there	O
+was	O
+a	O
+reduction	O
+in	O
+radicular	O
+symptoms	O
+.	O
+
+Three	O
+hours	O
+later	O
+,	O
+she	O
+complained	O
+of	O
+perineal	O
+numbness	B-Disease
+and	O
+lower	B-Disease
+extremity	I-Disease
+weakness	I-Disease
+.	O
+
+The	O
+neurologic	O
+evaluation	O
+revealed	O
+loss	B-Disease
+of	I-Disease
+sensation	I-Disease
+in	O
+the	O
+saddle	O
+area	O
+and	O
+medial	O
+aspect	O
+of	O
+her	O
+right	O
+leg	O
+.	O
+
+There	O
+was	O
+a	O
+decrease	O
+in	O
+the	O
+perception	O
+of	O
+pinprick	O
+test	O
+.	O
+
+Deep	O
+-	O
+tendon	O
+reflexes	O
+were	O
+decreased	O
+especially	O
+in	O
+the	O
+right	O
+leg	O
+.	O
+
+She	O
+was	O
+unable	O
+to	O
+urinate	O
+.	O
+
+The	O
+patient	O
+'	O
+s	O
+symptoms	O
+improved	O
+slightly	O
+over	O
+the	O
+next	O
+few	O
+hours	O
+.	O
+
+She	O
+had	O
+a	O
+gradual	O
+return	O
+of	O
+motor	O
+function	O
+and	O
+ability	O
+of	O
+feeling	O
+Foley	O
+catheter	O
+.	O
+
+All	O
+of	O
+the	O
+symptoms	O
+were	O
+completely	O
+resolved	O
+over	O
+the	O
+next	O
+8	O
+hours	O
+.	O
+
+CONCLUSION	O
+:	O
+Complications	O
+associated	O
+with	O
+epidural	O
+steroid	B-Chemical
+injections	O
+are	O
+rare	O
+.	O
+
+Clinical	O
+examination	O
+and	O
+continued	O
+vigilance	O
+for	O
+neurologic	B-Disease
+deterioration	I-Disease
+after	O
+epidural	O
+steroid	B-Chemical
+injections	O
+is	O
+important	O
+.	O
+
+High	O
+-	O
+dose	O
+testosterone	B-Chemical
+is	O
+associated	O
+with	O
+atherosclerosis	B-Disease
+in	O
+postmenopausal	O
+women	O
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+study	O
+the	O
+long	O
+-	O
+term	O
+effects	O
+of	O
+androgen	O
+treatment	O
+on	O
+atherosclerosis	B-Disease
+in	O
+postmenopausal	O
+women	O
+.	O
+
+METHODS	O
+:	O
+In	O
+a	O
+population	O
+-	O
+based	O
+study	O
+in	O
+513	O
+naturally	O
+postmenopausal	O
+women	O
+aged	O
+54	O
+-	O
+67	O
+years	O
+,	O
+we	O
+studied	O
+the	O
+association	O
+between	O
+self	O
+-	O
+reported	O
+intramuscularly	O
+administered	O
+high	O
+-	O
+dose	O
+estrogen	B-Chemical
+-	O
+testosterone	B-Chemical
+therapy	O
+(	O
+estradiol	B-Chemical
+-	I-Chemical
+and	I-Chemical
+testosterone	I-Chemical
+esters	I-Chemical
+)	O
+and	O
+aortic	O
+atherosclerosis	B-Disease
+.	O
+
+Aortic	O
+atherosclerosis	B-Disease
+was	O
+diagnosed	O
+by	O
+radiographic	O
+detection	O
+of	O
+calcified	O
+deposits	O
+in	O
+the	O
+abdominal	O
+aorta	O
+,	O
+which	O
+have	O
+been	O
+shown	O
+to	O
+reflect	O
+intima	O
+atherosclerosis	B-Disease
+.	O
+
+Hormone	O
+therapy	O
+users	O
+were	O
+compared	O
+with	O
+never	O
+users	O
+.	O
+
+RESULTS	O
+:	O
+Intramuscular	O
+hormone	O
+therapy	O
+use	O
+for	O
+1	O
+year	O
+or	O
+longer	O
+was	O
+reported	O
+by	O
+25	O
+women	O
+.	O
+
+In	O
+almost	O
+half	O
+of	O
+these	O
+women	O
+severe	O
+atherosclerosis	B-Disease
+of	O
+the	O
+aorta	O
+was	O
+present	O
+(	O
+n	O
+=	O
+11	O
+)	O
+,	O
+while	O
+in	O
+women	O
+without	O
+hormone	O
+use	O
+severe	O
+atherosclerosis	B-Disease
+of	O
+the	O
+aorta	O
+was	O
+present	O
+in	O
+less	O
+than	O
+20	O
+%	O
+(	O
+OR	O
+3	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+1	O
+-	O
+8	O
+.	O
+5	O
+,	O
+adjusted	O
+for	O
+age	O
+,	O
+years	O
+since	O
+menopause	O
+,	O
+smoking	O
+,	O
+and	O
+body	O
+mass	O
+index	O
+)	O
+.	O
+
+The	O
+association	O
+remained	O
+after	O
+additional	O
+adjustment	O
+for	O
+diabetes	B-Disease
+,	O
+cholesterol	B-Chemical
+level	O
+,	O
+systolic	O
+blood	O
+pressure	O
+,	O
+or	O
+alcohol	B-Chemical
+use	O
+.	O
+
+No	O
+association	O
+was	O
+found	O
+for	O
+hormone	O
+use	O
+less	O
+than	O
+1	O
+year	O
+.	O
+
+CONCLUSION	O
+:	O
+Our	O
+results	O
+suggest	O
+that	O
+high	O
+-	O
+dose	O
+testosterone	B-Chemical
+therapy	O
+may	O
+adversely	O
+affect	O
+atherosclerosis	B-Disease
+in	O
+postmenopausal	O
+women	O
+and	O
+indicate	O
+that	O
+androgen	O
+replacement	O
+in	O
+these	O
+women	O
+may	O
+not	O
+be	O
+harmless	O
+.	O
+
+Optimising	O
+stroke	B-Disease
+prevention	O
+in	O
+non	O
+-	O
+valvular	O
+atrial	B-Disease
+fibrillation	I-Disease
+.	O
+
+Atrial	B-Disease
+fibrillation	I-Disease
+is	O
+associated	O
+with	O
+substantial	O
+morbidity	O
+and	O
+mortality	O
+.	O
+
+Pooled	O
+data	O
+from	O
+trials	O
+comparing	O
+antithrombotic	O
+treatment	O
+with	O
+placebo	O
+have	O
+shown	O
+that	O
+warfarin	B-Chemical
+reduces	O
+the	O
+risk	O
+of	O
+stroke	B-Disease
+by	O
+62	O
+%	O
+,	O
+and	O
+that	O
+aspirin	B-Chemical
+alone	O
+reduces	O
+the	O
+risk	O
+by	O
+22	O
+%	O
+.	O
+
+Overall	O
+,	O
+in	O
+high	O
+-	O
+risk	O
+patients	O
+,	O
+warfarin	B-Chemical
+is	O
+superior	O
+to	O
+aspirin	B-Chemical
+in	O
+preventing	O
+strokes	B-Disease
+,	O
+with	O
+a	O
+relative	O
+risk	O
+reduction	O
+of	O
+36	O
+%	O
+.	O
+
+Ximelagatran	B-Chemical
+,	O
+an	O
+oral	O
+direct	O
+thrombin	O
+inhibitor	O
+,	O
+was	O
+found	O
+to	O
+be	O
+as	O
+efficient	O
+as	O
+vitamin	B-Chemical
+K	I-Chemical
+antagonist	O
+drugs	O
+in	O
+the	O
+prevention	O
+of	O
+embolic	B-Disease
+events	I-Disease
+,	O
+but	O
+has	O
+been	O
+recently	O
+withdrawn	O
+because	O
+of	O
+abnormal	B-Disease
+liver	I-Disease
+function	I-Disease
+tests	O
+.	O
+
+The	O
+ACTIVE	O
+-	O
+W	O
+(	O
+Atrial	B-Disease
+Fibrillation	I-Disease
+Clopidogrel	B-Chemical
+Trial	O
+with	O
+Irbesartan	B-Chemical
+for	O
+Prevention	O
+of	O
+Vascular	O
+Events	O
+)	O
+study	O
+has	O
+demonstrated	O
+that	O
+warfarin	B-Chemical
+is	O
+superior	O
+to	O
+platelet	O
+therapy	O
+(	O
+clopidogrel	B-Chemical
+plus	O
+aspirin	B-Chemical
+)	O
+in	O
+the	O
+prevention	O
+af	O
+embolic	B-Disease
+events	I-Disease
+.	O
+
+Idraparinux	B-Chemical
+,	O
+a	O
+Factor	O
+Xa	O
+inhibitor	O
+,	O
+is	O
+being	O
+evaluated	O
+in	O
+patients	O
+with	O
+atrial	B-Disease
+fibrillation	I-Disease
+.	O
+
+Angiotensin	B-Chemical
+-	O
+converting	O
+enzyme	O
+inhibitors	O
+and	O
+angiotensin	B-Chemical
+II	I-Chemical
+receptor	O
+-	O
+blocking	O
+drugs	O
+hold	O
+promise	O
+in	O
+atrial	B-Disease
+fibrillation	I-Disease
+through	O
+cardiac	B-Disease
+remodelling	I-Disease
+.	O
+
+Preliminary	O
+studies	O
+suggest	O
+that	O
+statins	B-Chemical
+could	O
+interfere	O
+with	O
+the	O
+risk	O
+of	O
+recurrence	O
+after	O
+electrical	O
+cardioversion	O
+.	O
+
+Finally	O
+,	O
+percutaneous	O
+methods	O
+for	O
+the	O
+exclusion	O
+of	O
+left	O
+atrial	O
+appendage	O
+are	O
+under	O
+investigation	O
+in	O
+high	O
+-	O
+risk	O
+patients	O
+.	O
+
+Anti	O
+-	O
+oxidant	O
+effects	O
+of	O
+atorvastatin	B-Chemical
+in	O
+dexamethasone	B-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+in	O
+the	O
+rat	O
+.	O
+
+1	O
+.	O
+
+Dexamethasone	B-Chemical
+(	O
+Dex	B-Chemical
+)	O
+-	O
+induced	O
+hypertension	B-Disease
+is	O
+characterized	O
+by	O
+endothelial	O
+dysfunction	O
+associated	O
+with	O
+nitric	B-Chemical
+oxide	I-Chemical
+(	O
+NO	B-Chemical
+)	O
+deficiency	O
+and	O
+increased	O
+superoxide	B-Chemical
+(	O
+O2	B-Chemical
+-	I-Chemical
+)	O
+production	O
+.	O
+
+Atorvastatin	B-Chemical
+(	O
+Ato	B-Chemical
+)	O
+possesses	O
+pleiotropic	O
+properties	O
+that	O
+have	O
+been	O
+reported	O
+to	O
+improve	O
+endothelial	O
+function	O
+through	O
+increased	O
+availability	O
+of	O
+NO	B-Chemical
+and	O
+reduced	O
+O2	B-Chemical
+-	I-Chemical
+production	O
+in	O
+various	O
+forms	O
+of	O
+hypertension	B-Disease
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+investigated	O
+whether	O
+50	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+,	O
+p	O
+.	O
+o	O
+.	O
+,	O
+Ato	B-Chemical
+could	O
+prevent	O
+endothelial	O
+NO	B-Chemical
+synthase	O
+(	O
+eNOS	O
+)	O
+downregulation	O
+and	O
+the	O
+increase	O
+in	O
+O2	B-Chemical
+-	I-Chemical
+in	O
+Sprague	O
+-	O
+Dawley	O
+(	O
+SD	O
+)	O
+rats	O
+,	O
+thereby	O
+reducing	O
+blood	O
+pressure	O
+.	O
+
+2	O
+.	O
+
+Male	O
+SD	O
+rats	O
+(	O
+n	O
+=	O
+30	O
+)	O
+were	O
+treated	O
+with	O
+Ato	B-Chemical
+(	O
+50	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+in	O
+drinking	O
+water	O
+)	O
+or	O
+tap	O
+water	O
+for	O
+15	O
+days	O
+.	O
+
+Dexamethasone	B-Chemical
+(	O
+10	O
+microg	O
+/	O
+kg	O
+per	O
+day	O
+,	O
+s	O
+.	O
+c	O
+.	O
+)	O
+or	O
+saline	O
+was	O
+started	O
+after	O
+4	O
+days	O
+in	O
+Ato	B-Chemical
+-	O
+treated	O
+and	O
+non	O
+-	O
+treated	O
+rats	O
+and	O
+continued	O
+for	O
+11	O
+-	O
+13	O
+days	O
+.	O
+
+Systolic	O
+blood	O
+pressure	O
+(	O
+SBP	O
+)	O
+was	O
+measured	O
+on	O
+alternate	O
+days	O
+using	O
+the	O
+tail	O
+-	O
+cuff	O
+method	O
+.	O
+
+Endothelial	O
+function	O
+was	O
+assessed	O
+by	O
+acetylcholine	B-Chemical
+-	O
+induced	O
+vasorelaxation	O
+and	O
+phenylephrine	B-Chemical
+-	O
+induced	O
+vasoconstriction	O
+in	O
+aortic	O
+segments	O
+.	O
+
+Vascular	O
+eNOS	O
+mRNA	O
+was	O
+assessed	O
+by	O
+semi	O
+-	O
+quantitative	O
+reverse	O
+transcription	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+.	O
+
+3	O
+.	O
+
+In	O
+rats	O
+treated	O
+with	O
+Dex	B-Chemical
+alone	O
+,	O
+SBP	O
+was	O
+increased	O
+from	O
+109	O
++	O
+/	O
+-	O
+2	O
+to	O
+133	O
++	O
+/	O
+-	O
+2	O
+mmHg	O
+on	O
+Days	O
+4	O
+and	O
+Day	O
+14	O
+,	O
+respectively	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+In	O
+the	O
+Ato	B-Chemical
++	O
+Dex	B-Chemical
+group	O
+,	O
+SBP	O
+was	O
+increased	O
+from	O
+113	O
++	O
+/	O
+-	O
+2	O
+to	O
+119	O
++	O
+/	O
+-	O
+2	O
+mmHg	O
+on	O
+Days	O
+4	O
+to	O
+14	O
+,	O
+respectively	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+but	O
+was	O
+significantly	O
+lower	O
+than	O
+SBP	O
+in	O
+the	O
+group	O
+treated	O
+with	O
+Dex	B-Chemical
+alone	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Endothelial	O
+-	O
+dependent	O
+relaxation	O
+and	O
+eNOS	O
+mRNA	O
+expression	O
+were	O
+greater	O
+in	O
+the	O
+Dex	B-Chemical
++	O
+Ato	B-Chemical
+group	O
+than	O
+in	O
+the	O
+Dex	B-Chemical
+only	O
+group	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+and	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+,	O
+respectively	O
+)	O
+.	O
+
+Aortic	O
+superoxide	B-Chemical
+production	O
+was	O
+lower	O
+in	O
+the	O
+Dex	B-Chemical
++	O
+Ato	B-Chemical
+group	O
+compared	O
+with	O
+the	O
+group	O
+treated	O
+with	O
+Dex	B-Chemical
+alone	O
+(	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+4	O
+.	O
+
+Treatment	O
+with	O
+Ato	B-Chemical
+improved	O
+endothelial	O
+function	O
+,	O
+reduced	O
+superoxide	B-Chemical
+production	O
+and	O
+reduced	O
+SBP	O
+in	O
+Dex	B-Chemical
+-	O
+treated	O
+SD	O
+rats	O
+.	O
+
+Severe	O
+citrate	B-Chemical
+toxicity	B-Disease
+complicating	O
+volunteer	O
+apheresis	O
+platelet	O
+donation	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+severe	O
+citrate	B-Chemical
+toxicity	B-Disease
+during	O
+volunteer	O
+donor	O
+apheresis	O
+platelet	O
+collection	O
+.	O
+
+The	O
+donor	O
+was	O
+a	O
+40	O
+-	O
+year	O
+-	O
+old	O
+female	O
+,	O
+first	O
+-	O
+time	O
+apheresis	O
+platelet	O
+donor	O
+.	O
+
+Past	O
+medical	O
+history	O
+was	O
+remarkable	O
+for	O
+hypertension	B-Disease
+,	O
+hyperlipidemia	B-Disease
+,	O
+and	O
+depression	B-Disease
+.	O
+
+Reported	O
+medications	O
+included	O
+bumetanide	B-Chemical
+,	O
+pravastatin	B-Chemical
+,	O
+and	O
+paroxetine	B-Chemical
+.	O
+
+Thirty	O
+minutes	O
+from	O
+the	O
+start	O
+of	O
+the	O
+procedure	O
+,	O
+the	O
+donor	O
+noted	O
+tingling	O
+around	O
+the	O
+mouth	O
+,	O
+hands	O
+,	O
+and	O
+feet	O
+.	O
+
+She	O
+then	O
+very	O
+rapidly	O
+developed	O
+acute	O
+onset	O
+of	O
+severe	O
+facial	O
+and	O
+extremity	O
+tetany	B-Disease
+.	O
+
+Empirical	O
+treatment	O
+with	O
+intravenous	O
+calcium	B-Chemical
+gluconate	I-Chemical
+was	O
+initiated	O
+,	O
+and	O
+muscle	B-Disease
+contractions	I-Disease
+slowly	O
+subsided	O
+over	O
+approximately	O
+10	O
+to	O
+15	O
+minutes	O
+.	O
+
+The	O
+events	O
+are	O
+consistent	O
+with	O
+a	O
+severe	O
+reaction	O
+to	O
+calcium	B-Chemical
+chelation	O
+by	O
+sodium	B-Chemical
+citrate	I-Chemical
+anticoagulant	O
+resulting	O
+in	O
+symptomatic	O
+systemic	O
+hypocalcemia	B-Disease
+.	O
+
+Upon	O
+additional	O
+retrospective	O
+analysis	O
+,	O
+it	O
+was	O
+noted	O
+that	O
+bumetanide	B-Chemical
+is	O
+a	O
+loop	B-Chemical
+diuretic	I-Chemical
+that	O
+may	O
+cause	O
+significant	O
+hypocalcemia	B-Disease
+.	O
+
+We	O
+conclude	O
+that	O
+careful	O
+screening	O
+for	O
+medications	O
+and	O
+underlying	O
+conditions	O
+predisposing	O
+to	O
+hypocalcemia	B-Disease
+is	O
+recommended	O
+to	O
+help	O
+prevent	O
+severe	O
+reactions	O
+due	O
+to	O
+citrate	B-Chemical
+toxicity	B-Disease
+.	O
+
+Laboratory	O
+measurement	O
+of	O
+pre	O
+-	O
+procedure	O
+serum	O
+calcium	B-Chemical
+levels	O
+in	O
+selected	O
+donors	O
+may	O
+identify	O
+cases	O
+requiring	O
+heightened	O
+vigilance	O
+.	O
+
+The	O
+case	O
+also	O
+illustrates	O
+the	O
+importance	O
+of	O
+maintaining	O
+preparedness	O
+for	O
+managing	O
+rare	O
+but	O
+serious	O
+reactions	O
+in	O
+volunteer	O
+apheresis	O
+blood	O
+donors	O
+.	O
+
+Sirolimus	B-Chemical
+-	O
+associated	O
+proteinuria	B-Disease
+and	O
+renal	B-Disease
+dysfunction	I-Disease
+.	O
+
+Sirolimus	B-Chemical
+is	O
+a	O
+novel	O
+immunosuppressant	O
+with	O
+potent	O
+antiproliferative	O
+actions	O
+through	O
+its	O
+ability	O
+to	O
+inhibit	O
+the	O
+raptor	O
+-	O
+containing	O
+mammalian	O
+target	O
+of	O
+rapamycin	B-Chemical
+protein	O
+kinase	O
+.	O
+
+Sirolimus	B-Chemical
+represents	O
+a	O
+major	O
+therapeutic	O
+advance	O
+in	O
+the	O
+prevention	O
+of	O
+acute	O
+renal	O
+allograft	O
+rejection	O
+and	O
+chronic	O
+allograft	O
+nephropathy	B-Disease
+.	O
+
+Its	O
+role	O
+in	O
+the	O
+therapy	O
+of	O
+glomerulonephritis	B-Disease
+,	O
+autoimmunity	B-Disease
+,	O
+cystic	B-Disease
+renal	I-Disease
+diseases	I-Disease
+and	O
+renal	B-Disease
+cancer	I-Disease
+is	O
+under	O
+investigation	O
+.	O
+
+Because	O
+sirolimus	B-Chemical
+does	O
+not	O
+share	O
+the	O
+vasomotor	O
+renal	O
+adverse	O
+effects	O
+exhibited	O
+by	O
+calcineurin	O
+inhibitors	O
+,	O
+it	O
+has	O
+been	O
+designated	O
+a	O
+'	O
+non	O
+-	O
+nephrotoxic	B-Disease
+drug	O
+'	O
+.	O
+
+However	O
+,	O
+clinical	O
+reports	O
+suggest	O
+that	O
+,	O
+under	O
+some	O
+circumstances	O
+,	O
+sirolimus	B-Chemical
+is	O
+associated	O
+with	O
+proteinuria	B-Disease
+and	O
+acute	B-Disease
+renal	I-Disease
+dysfunction	I-Disease
+.	O
+
+A	O
+common	O
+risk	O
+factor	O
+appears	O
+to	O
+be	O
+presence	O
+of	O
+pre	O
+-	O
+existing	O
+chronic	B-Disease
+renal	I-Disease
+damage	I-Disease
+.	O
+
+The	O
+mechanisms	O
+of	O
+sirolimus	B-Chemical
+-	O
+associated	O
+proteinuria	B-Disease
+are	O
+multifactorial	O
+and	O
+may	O
+be	O
+due	O
+to	O
+an	O
+increase	O
+in	O
+glomerular	O
+capillary	O
+pressure	O
+following	O
+calcineurin	O
+inhibitor	O
+withdrawal	O
+.	O
+
+It	O
+has	O
+also	O
+been	O
+suggested	O
+that	O
+sirolimus	B-Chemical
+directly	O
+causes	O
+increased	O
+glomerular	O
+permeability	O
+/	O
+injury	O
+,	O
+but	O
+evidence	O
+for	O
+this	O
+mechanism	O
+is	O
+currently	O
+inconclusive	O
+.	O
+
+The	O
+acute	B-Disease
+renal	I-Disease
+dysfunction	I-Disease
+associated	O
+with	O
+sirolimus	B-Chemical
+(	O
+such	O
+as	O
+in	O
+delayed	O
+graft	O
+function	O
+)	O
+may	O
+be	O
+due	O
+to	O
+suppression	O
+of	O
+compensatory	O
+renal	O
+cell	O
+proliferation	O
+and	O
+survival	O
+/	O
+repair	O
+processes	O
+.	O
+
+Although	O
+these	O
+adverse	O
+effects	O
+occur	O
+in	O
+some	O
+patients	O
+,	O
+their	O
+occurrence	O
+could	O
+be	O
+minimised	O
+by	O
+knowledge	O
+of	O
+the	O
+molecular	O
+effects	O
+of	O
+sirolimus	B-Chemical
+on	O
+the	O
+kidney	O
+,	O
+the	O
+use	O
+of	O
+sirolimus	B-Chemical
+in	O
+appropriate	O
+patient	O
+populations	O
+,	O
+close	O
+monitoring	O
+of	O
+proteinuria	B-Disease
+and	O
+renal	O
+function	O
+,	O
+use	O
+of	O
+angiotensin	B-Chemical
+-	O
+converting	O
+enzyme	O
+inhibitors	O
+or	O
+angiotensin	B-Chemical
+II	I-Chemical
+receptor	O
+blockers	O
+if	O
+proteinuria	B-Disease
+occurs	O
+and	O
+withdrawal	O
+if	O
+needed	O
+.	O
+
+Further	O
+long	O
+-	O
+term	O
+analysis	O
+of	O
+renal	O
+allograft	O
+studies	O
+using	O
+sirolimus	B-Chemical
+as	O
+de	O
+novo	O
+immunosuppression	O
+along	O
+with	O
+clinical	O
+and	O
+laboratory	O
+studies	O
+will	O
+refine	O
+these	O
+issues	O
+in	O
+the	O
+future	O
+.	O
+
+Proteinuria	B-Disease
+after	O
+conversion	O
+to	O
+sirolimus	B-Chemical
+in	O
+renal	O
+transplant	O
+recipients	O
+.	O
+
+Sirolimus	B-Chemical
+(	O
+SRL	B-Chemical
+)	O
+is	O
+a	O
+new	O
+,	O
+potent	O
+immunosuppressive	O
+agent	O
+.	O
+
+More	O
+recently	O
+,	O
+proteinuria	B-Disease
+has	O
+been	O
+reported	O
+as	O
+a	O
+consequence	O
+of	O
+sirolimus	B-Chemical
+therapy	O
+,	O
+although	O
+the	O
+mechanism	O
+has	O
+remained	O
+unclear	O
+.	O
+
+We	O
+retrospectively	O
+examined	O
+the	O
+records	O
+of	O
+25	O
+renal	O
+transplant	O
+patients	O
+,	O
+who	O
+developed	O
+or	O
+displayed	O
+increased	O
+proteinuria	B-Disease
+after	O
+SRL	B-Chemical
+conversion	O
+.	O
+
+The	O
+patient	O
+cohort	O
+(	O
+14	O
+men	O
+,	O
+11	O
+women	O
+)	O
+was	O
+treated	O
+with	O
+SRL	B-Chemical
+as	O
+conversion	O
+therapy	O
+,	O
+due	O
+to	O
+chronic	B-Disease
+allograft	I-Disease
+nephropathy	I-Disease
+(	O
+CAN	B-Disease
+)	O
+(	O
+n	O
+=	O
+15	O
+)	O
+neoplasia	B-Disease
+(	O
+n	O
+=	O
+8	O
+)	O
+;	O
+Kaposi	B-Disease
+'	I-Disease
+s	I-Disease
+sarcoma	I-Disease
+,	O
+Four	O
+skin	B-Disease
+cancers	I-Disease
+,	O
+One	O
+intestinal	B-Disease
+tumors	I-Disease
+,	O
+One	O
+renal	B-Disease
+cell	I-Disease
+carsinom	I-Disease
+)	O
+or	O
+BK	O
+virus	O
+nephropathy	B-Disease
+(	O
+n	O
+=	O
+2	O
+)	O
+.	O
+
+SRL	B-Chemical
+was	O
+started	O
+at	O
+a	O
+mean	O
+of	O
+78	O
++	O
+/	O
+-	O
+42	O
+(	O
+15	O
+to	O
+163	O
+)	O
+months	O
+after	O
+transplantation	O
+.	O
+
+Mean	O
+follow	O
+-	O
+up	O
+on	O
+SRL	B-Chemical
+therapy	O
+was	O
+20	O
++	O
+/	O
+-	O
+12	O
+(	O
+6	O
+to	O
+43	O
+)	O
+months	O
+.	O
+
+Proteinuria	B-Disease
+increased	O
+from	O
+0	O
+.	O
+445	O
+(	O
+0	O
+to	O
+1	O
+.	O
+5	O
+)	O
+g	O
+/	O
+d	O
+before	O
+conversion	O
+to	O
+3	O
+.	O
+2	O
+g	O
+/	O
+dL	O
+(	O
+0	O
+.	O
+2	O
+to	O
+12	O
+)	O
+after	O
+conversion	O
+(	O
+P	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Before	O
+conversion	O
+8	O
+(	O
+32	O
+%	O
+)	O
+patients	O
+had	O
+no	O
+proteinuria	B-Disease
+,	O
+whereas	O
+afterwards	O
+all	O
+patients	O
+had	O
+proteinuria	B-Disease
+.	O
+
+In	O
+28	O
+%	O
+of	O
+patients	O
+proteinuria	B-Disease
+remained	O
+unchanged	O
+,	O
+whereas	O
+it	O
+increased	O
+in	O
+68	O
+%	O
+of	O
+patients	O
+.	O
+
+In	O
+40	O
+%	O
+it	O
+increased	O
+by	O
+more	O
+than	O
+100	O
+%	O
+.	O
+
+Twenty	O
+-	O
+eight	O
+percent	O
+of	O
+patients	O
+showed	O
+increased	O
+proteinuria	B-Disease
+to	O
+the	O
+nephrotic	B-Disease
+range	O
+.	O
+
+Biopsies	O
+performed	O
+in	O
+five	O
+patients	O
+revealed	O
+new	O
+pathological	O
+changes	O
+:	O
+One	O
+membranoproliferative	B-Disease
+glomerulopathy	I-Disease
+and	O
+interstitial	B-Disease
+nephritis	I-Disease
+.	O
+
+These	O
+patients	O
+showed	O
+persistently	O
+good	O
+graft	O
+function	O
+.	O
+
+Serum	O
+creatinine	B-Chemical
+values	O
+did	O
+not	O
+change	O
+significantly	O
+:	O
+1	O
+.	O
+98	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+mg	O
+/	O
+dL	O
+before	O
+SRL	B-Chemical
+therapy	O
+and	O
+2	O
+.	O
+53	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+mg	O
+/	O
+dL	O
+at	O
+last	O
+follow	O
+-	O
+up	O
+(	O
+P	O
+=	O
+.	O
+14	O
+)	O
+.	O
+
+Five	O
+grafts	O
+were	O
+lost	O
+and	O
+the	O
+patients	O
+returned	O
+to	O
+dialysis	O
+.	O
+
+Five	O
+patients	O
+displayed	O
+CAN	B-Disease
+and	O
+Kaposi	B-Disease
+'	I-Disease
+s	I-Disease
+sarcoma	I-Disease
+.	O
+
+Mean	O
+urinary	O
+protein	O
+of	O
+patients	O
+who	O
+returned	O
+to	O
+dialysis	O
+was	O
+1	O
+.	O
+26	O
+(	O
+0	O
+.	O
+5	O
+to	O
+3	O
+.	O
+5	O
+)	O
+g	O
+/	O
+d	O
+before	O
+and	O
+4	O
+.	O
+7	O
+(	O
+3	O
+to	O
+12	O
+)	O
+g	O
+/	O
+d	O
+after	O
+conversion	O
+(	O
+P	O
+=	O
+.	O
+01	O
+)	O
+.	O
+
+Mean	O
+serum	O
+creatinine	B-Chemical
+level	O
+before	O
+conversion	O
+was	O
+2	O
+.	O
+21	O
+mg	O
+/	O
+dL	O
+and	O
+thereafter	O
+,	O
+4	O
+.	O
+93	O
+mg	O
+/	O
+dL	O
+(	O
+P	O
+=	O
+.	O
+02	O
+)	O
+.	O
+
+Heavy	O
+proteinuria	B-Disease
+was	O
+common	O
+after	O
+the	O
+use	O
+of	O
+SRL	B-Chemical
+as	O
+rescue	O
+therapy	O
+for	O
+renal	O
+transplantation	O
+.	O
+
+Therefore	O
+,	O
+conversion	O
+should	O
+be	O
+considered	O
+for	O
+patients	O
+who	O
+have	O
+not	O
+developed	O
+advanced	O
+CAN	B-Disease
+and	O
+proteinuria	B-Disease
+.	O
+
+The	O
+possibility	O
+of	O
+de	O
+novo	O
+glomerular	O
+pathology	O
+under	O
+SRL	B-Chemical
+treatment	O
+requires	O
+further	O
+investigation	O
+by	O
+renal	O
+biopsy	O
+.	O
+
+Long	O
+-	O
+term	O
+follow	O
+-	O
+up	O
+of	O
+ifosfamide	B-Chemical
+renal	B-Disease
+toxicity	I-Disease
+in	O
+children	O
+treated	O
+for	O
+malignant	B-Disease
+mesenchymal	I-Disease
+tumors	I-Disease
+:	O
+an	O
+International	O
+Society	O
+of	O
+Pediatric	O
+Oncology	O
+report	O
+.	O
+
+The	O
+renal	O
+function	O
+of	O
+74	O
+children	O
+with	O
+malignant	B-Disease
+mesenchymal	I-Disease
+tumors	I-Disease
+in	O
+complete	O
+remission	O
+and	O
+who	O
+have	O
+received	O
+the	O
+same	O
+ifosfamide	B-Chemical
+chemotherapy	O
+protocol	O
+(	O
+International	O
+Society	O
+of	O
+Pediatric	O
+Oncology	O
+Malignant	B-Disease
+Mesenchymal	I-Disease
+Tumor	I-Disease
+Study	O
+84	O
+[	O
+SIOP	O
+MMT	O
+84	O
+]	O
+)	O
+were	O
+studied	O
+1	O
+year	O
+after	O
+the	O
+completion	O
+of	O
+treatment	O
+.	O
+
+Total	O
+cumulative	O
+doses	O
+were	O
+36	O
+or	O
+60	O
+g	O
+/	O
+m2	O
+of	O
+ifosfamide	B-Chemical
+(	O
+six	O
+or	O
+10	O
+cycles	O
+of	O
+ifosfamide	B-Chemical
+,	I-Chemical
+vincristine	I-Chemical
+,	I-Chemical
+and	I-Chemical
+dactinomycin	I-Chemical
+[	O
+IVA	B-Chemical
+]	O
+)	O
+.	O
+
+None	O
+of	O
+them	O
+had	O
+received	O
+cisplatin	B-Chemical
+chemotherapy	O
+.	O
+
+Ages	O
+ranged	O
+from	O
+4	O
+months	O
+to	O
+17	O
+years	O
+;	O
+58	O
+patients	O
+were	O
+males	O
+and	O
+42	O
+females	O
+.	O
+
+The	O
+most	O
+common	O
+primary	O
+tumor	B-Disease
+site	O
+was	O
+the	O
+head	O
+and	O
+neck	O
+.	O
+
+Renal	O
+function	O
+was	O
+investigated	O
+by	O
+measuring	O
+plasma	O
+and	O
+urinary	O
+electrolytes	O
+,	O
+glucosuria	B-Disease
+,	O
+proteinuria	B-Disease
+,	O
+aminoaciduria	B-Disease
+,	O
+urinary	O
+pH	O
+,	O
+osmolarity	O
+,	O
+creatinine	B-Chemical
+clearance	O
+,	O
+phosphate	B-Chemical
+tubular	O
+reabsorption	O
+,	O
+beta	O
+2	O
+microglobulinuria	O
+,	O
+and	O
+lysozymuria	O
+.	O
+
+Fifty	O
+-	O
+eight	O
+patients	O
+(	O
+78	O
+%	O
+)	O
+had	O
+normal	O
+renal	O
+tests	O
+,	O
+whereas	O
+16	O
+patients	O
+(	O
+22	O
+%	O
+)	O
+had	O
+renal	B-Disease
+abnormalities	I-Disease
+.	O
+
+Two	O
+subsets	O
+of	O
+patients	O
+were	O
+identified	O
+from	O
+this	O
+latter	O
+group	O
+:	O
+the	O
+first	O
+included	O
+four	O
+patients	O
+(	O
+5	O
+%	O
+of	O
+the	O
+total	O
+population	O
+)	O
+who	O
+developed	O
+major	O
+toxicity	B-Disease
+resulting	O
+in	O
+Fanconi	B-Disease
+'	I-Disease
+s	I-Disease
+syndrome	I-Disease
+(	O
+TDFS	B-Disease
+)	O
+;	O
+and	O
+the	O
+second	O
+group	O
+included	O
+five	O
+patients	O
+with	O
+elevated	O
+beta	O
+2	O
+microglobulinuria	O
+and	O
+low	O
+phosphate	B-Chemical
+reabsorption	O
+.	O
+
+The	O
+remaining	O
+seven	O
+patients	O
+had	O
+isolated	O
+beta	O
+2	O
+microglobulinuria	O
+.	O
+
+Severe	O
+toxicity	B-Disease
+was	O
+correlated	O
+with	O
+the	O
+higher	O
+cumulative	O
+dose	O
+of	O
+60	O
+g	O
+/	O
+m2	O
+of	O
+ifosfamide	B-Chemical
+,	O
+a	O
+younger	O
+age	O
+(	O
+less	O
+than	O
+2	O
+1	O
+/	O
+2	O
+years	O
+old	O
+)	O
+,	O
+and	O
+a	O
+predominance	O
+of	O
+vesicoprostatic	O
+tumor	B-Disease
+involvement	O
+.	O
+
+This	O
+low	O
+percentage	O
+(	O
+5	O
+%	O
+)	O
+of	O
+TDFS	O
+must	O
+be	O
+evaluated	O
+with	O
+respect	O
+to	O
+the	O
+efficacy	O
+of	O
+ifosfamide	B-Chemical
+in	O
+the	O
+treatment	O
+of	O
+mesenchymal	B-Disease
+tumors	I-Disease
+in	O
+children	O
+.	O
+
+Progressive	O
+myopathy	B-Disease
+with	O
+up	O
+-	O
+regulation	O
+of	O
+MHC	O
+-	O
+I	O
+associated	O
+with	O
+statin	B-Chemical
+therapy	O
+.	O
+
+Statins	B-Chemical
+can	O
+cause	O
+a	O
+necrotizing	O
+myopathy	B-Disease
+and	O
+hyperCKaemia	B-Disease
+which	O
+is	O
+reversible	O
+on	O
+cessation	O
+of	O
+the	O
+drug	O
+.	O
+
+What	O
+is	O
+less	O
+well	O
+known	O
+is	O
+a	O
+phenomenon	O
+whereby	O
+statins	B-Chemical
+may	O
+induce	O
+a	O
+myopathy	B-Disease
+,	O
+which	O
+persists	O
+or	O
+may	O
+progress	O
+after	O
+stopping	O
+the	O
+drug	O
+.	O
+
+We	O
+investigated	O
+the	O
+muscle	O
+pathology	O
+in	O
+8	O
+such	O
+cases	O
+.	O
+
+All	O
+had	O
+myofibre	O
+necrosis	B-Disease
+but	O
+only	O
+3	O
+had	O
+an	O
+inflammatory	O
+infiltrate	O
+.	O
+
+In	O
+all	O
+cases	O
+there	O
+was	O
+diffuse	O
+or	O
+multifocal	O
+up	O
+-	O
+regulation	O
+of	O
+MHC	O
+-	O
+I	O
+expression	O
+even	O
+in	O
+non	O
+-	O
+necrotic	B-Disease
+fibres	O
+.	O
+
+Progressive	O
+improvement	O
+occurred	O
+in	O
+7	O
+cases	O
+after	O
+commencement	O
+of	O
+prednisolone	B-Chemical
+and	O
+methotrexate	B-Chemical
+,	O
+and	O
+in	O
+one	O
+case	O
+spontaneously	O
+.	O
+
+These	O
+observations	O
+suggest	O
+that	O
+statins	B-Chemical
+may	O
+initiate	O
+an	O
+immune	O
+-	O
+mediated	O
+myopathy	B-Disease
+that	O
+persists	O
+after	O
+withdrawal	O
+of	O
+the	O
+drug	O
+and	O
+responds	O
+to	O
+immunosuppressive	O
+therapy	O
+.	O
+
+The	O
+mechanism	O
+of	O
+this	O
+myopathy	B-Disease
+is	O
+uncertain	O
+but	O
+may	O
+involve	O
+the	O
+induction	O
+by	O
+statins	B-Chemical
+of	O
+an	O
+endoplasmic	O
+reticulum	O
+stress	O
+response	O
+with	O
+associated	O
+up	O
+-	O
+regulation	O
+of	O
+MHC	O
+-	O
+I	O
+expression	O
+and	O
+antigen	O
+presentation	O
+by	O
+muscle	O
+fibres	O
+.	O
+
+Use	O
+of	O
+chromosome	O
+substitution	O
+strains	O
+to	O
+identify	O
+seizure	B-Disease
+susceptibility	O
+loci	O
+in	O
+mice	O
+.	O
+
+Seizure	B-Disease
+susceptibility	O
+varies	O
+among	O
+inbred	O
+mouse	O
+strains	O
+.	O
+
+Chromosome	O
+substitution	O
+strains	O
+(	O
+CSS	O
+)	O
+,	O
+in	O
+which	O
+a	O
+single	O
+chromosome	O
+from	O
+one	O
+inbred	O
+strain	O
+(	O
+donor	O
+)	O
+has	O
+been	O
+transferred	O
+onto	O
+a	O
+second	O
+strain	O
+(	O
+host	O
+)	O
+by	O
+repeated	O
+backcrossing	O
+,	O
+may	O
+be	O
+used	O
+to	O
+identify	O
+quantitative	O
+trait	O
+loci	O
+(	O
+QTLs	O
+)	O
+that	O
+contribute	O
+to	O
+seizure	B-Disease
+susceptibility	O
+.	O
+
+QTLs	O
+for	O
+susceptibility	O
+to	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+,	O
+a	O
+model	O
+of	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+,	O
+have	O
+not	O
+been	O
+reported	O
+,	O
+and	O
+CSS	O
+have	O
+not	O
+previously	O
+been	O
+used	O
+to	O
+localize	O
+seizure	B-Disease
+susceptibility	O
+genes	O
+.	O
+
+We	O
+report	O
+QTLs	O
+identified	O
+using	O
+a	O
+B6	O
+(	O
+host	O
+)	O
+x	O
+A	O
+/	O
+J	O
+(	O
+donor	O
+)	O
+CSS	O
+panel	O
+to	O
+localize	O
+genes	O
+involved	O
+in	O
+susceptibility	O
+to	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+.	O
+
+Three	O
+hundred	O
+fifty	O
+-	O
+five	O
+adult	O
+male	O
+CSS	O
+mice	O
+,	O
+58	O
+B6	O
+,	O
+and	O
+39	O
+A	O
+/	O
+J	O
+were	O
+tested	O
+for	O
+susceptibility	O
+to	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+.	O
+
+Highest	O
+stage	O
+reached	O
+and	O
+latency	O
+to	O
+each	O
+stage	O
+were	O
+recorded	O
+for	O
+all	O
+mice	O
+.	O
+
+B6	O
+mice	O
+were	O
+resistant	O
+to	O
+seizures	B-Disease
+and	O
+slower	O
+to	O
+reach	O
+stages	O
+compared	O
+to	O
+A	O
+/	O
+J	O
+mice	O
+.	O
+
+The	O
+CSS	O
+for	O
+Chromosomes	O
+10	O
+and	O
+18	O
+progressed	O
+to	O
+the	O
+most	O
+severe	O
+stages	O
+,	O
+diverging	O
+dramatically	O
+from	O
+the	O
+B6	O
+phenotype	O
+.	O
+
+Latencies	O
+to	O
+stages	O
+were	O
+also	O
+significantly	O
+shorter	O
+for	O
+CSS10	O
+and	O
+CSS18	O
+mice	O
+.	O
+
+CSS	O
+mapping	O
+suggests	O
+seizure	B-Disease
+susceptibility	O
+loci	O
+on	O
+mouse	O
+Chromosomes	O
+10	O
+and	O
+18	O
+.	O
+
+This	O
+approach	O
+provides	O
+a	O
+framework	O
+for	O
+identifying	O
+potentially	O
+novel	O
+homologous	O
+candidate	O
+genes	O
+for	O
+human	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+.	O
+
+In	O
+vitro	O
+characterization	O
+of	O
+parasympathetic	O
+and	O
+sympathetic	O
+responses	O
+in	O
+cyclophosphamide	B-Chemical
+-	O
+induced	O
+cystitis	B-Disease
+in	O
+the	O
+rat	O
+.	O
+
+In	O
+cyclophosphamide	B-Chemical
+-	O
+induced	O
+cystitis	B-Disease
+in	O
+the	O
+rat	O
+,	O
+detrusor	O
+function	O
+is	O
+impaired	O
+and	O
+the	O
+expression	O
+and	O
+effects	O
+of	O
+muscarinic	O
+receptors	O
+altered	O
+.	O
+
+Whether	O
+or	O
+not	O
+the	O
+neuronal	O
+transmission	O
+may	O
+be	O
+affected	O
+by	O
+cystitis	B-Disease
+was	O
+presently	O
+investigated	O
+.	O
+
+Responses	O
+of	O
+urinary	O
+strip	O
+preparations	O
+from	O
+control	O
+and	O
+cyclophosphamide	B-Chemical
+-	O
+pretreated	O
+rats	O
+to	O
+electrical	O
+field	O
+stimulation	O
+and	O
+to	O
+agonists	O
+were	O
+assessed	O
+in	O
+the	O
+absence	O
+and	O
+presence	O
+of	O
+muscarinic	O
+,	O
+adrenergic	O
+and	O
+purinergic	O
+receptor	O
+antagonists	O
+.	O
+
+Generally	O
+,	O
+atropine	B-Chemical
+reduced	O
+contractions	O
+,	O
+but	O
+in	O
+contrast	O
+to	O
+controls	O
+,	O
+it	O
+also	O
+reduced	O
+responses	O
+to	O
+low	O
+electrical	O
+field	O
+stimulation	O
+intensity	O
+(	O
+1	O
+-	O
+5	O
+Hz	O
+)	O
+in	O
+inflamed	O
+preparations	O
+.	O
+
+In	O
+both	O
+types	O
+,	O
+purinoceptor	O
+desensitization	O
+with	O
+alpha	B-Chemical
+,	I-Chemical
+beta	I-Chemical
+-	I-Chemical
+methylene	I-Chemical
+adenosine	I-Chemical
+-	I-Chemical
+5	I-Chemical
+'	I-Chemical
+-	I-Chemical
+triphosphate	I-Chemical
+(	O
+alpha	B-Chemical
+,	I-Chemical
+beta	I-Chemical
+-	I-Chemical
+meATP	I-Chemical
+)	O
+caused	O
+further	O
+reductions	O
+at	O
+low	O
+frequencies	O
+(	O
+<	O
+10	O
+Hz	O
+)	O
+.	O
+
+The	O
+muscarinic	O
+receptor	O
+antagonists	O
+atropine	B-Chemical
+,	O
+4	B-Chemical
+-	I-Chemical
+diphenylacetoxy	I-Chemical
+-	I-Chemical
+N	I-Chemical
+-	I-Chemical
+methylpiperidine	I-Chemical
+(	O
+4	B-Chemical
+-	I-Chemical
+DAMP	I-Chemical
+)	O
+(	O
+'	O
+M	O
+(	O
+1	O
+)	O
+/	O
+M	O
+(	O
+3	O
+)	O
+/	O
+M	O
+(	O
+5	O
+)	O
+-	O
+selective	O
+'	O
+)	O
+,	O
+methoctramine	B-Chemical
+(	O
+'	O
+M	O
+(	O
+2	O
+)	O
+-	O
+selective	O
+'	O
+)	O
+and	O
+pirenzepine	B-Chemical
+(	O
+'	O
+M	O
+(	O
+1	O
+)	O
+-	O
+selective	O
+'	O
+)	O
+antagonized	O
+the	O
+tonic	O
+component	O
+of	O
+the	O
+electrical	O
+field	O
+stimulation	O
+-	O
+evoked	O
+contractile	O
+response	O
+more	O
+potently	O
+than	O
+the	O
+phasic	O
+component	O
+.	O
+
+4	B-Chemical
+-	I-Chemical
+DAMP	I-Chemical
+inhibited	O
+the	O
+tonic	O
+contractions	O
+in	O
+controls	O
+more	O
+potently	O
+than	O
+methoctramine	B-Chemical
+and	O
+pirenzepine	B-Chemical
+.	O
+
+In	O
+inflamed	O
+preparations	O
+,	O
+the	O
+muscarinic	O
+receptor	O
+antagonism	O
+on	O
+the	O
+phasic	O
+component	O
+of	O
+the	O
+electrical	O
+field	O
+stimulation	O
+-	O
+evoked	O
+contraction	O
+was	O
+decreased	O
+and	O
+the	O
+pirenzepine	B-Chemical
+and	O
+4	B-Chemical
+-	I-Chemical
+DAMP	I-Chemical
+antagonism	O
+on	O
+the	O
+tonic	O
+component	O
+was	O
+much	O
+less	O
+efficient	O
+than	O
+in	O
+controls	O
+.	O
+
+In	O
+contrast	O
+to	O
+controls	O
+,	O
+methoctramine	B-Chemical
+increased	O
+-	O
+-	O
+instead	O
+of	O
+decreased	O
+-	O
+-	O
+the	O
+tonic	O
+responses	O
+at	O
+high	O
+frequencies	O
+.	O
+
+While	O
+contractions	O
+to	O
+carbachol	B-Chemical
+and	O
+ATP	B-Chemical
+were	O
+the	O
+same	O
+in	O
+inflamed	O
+and	O
+in	O
+control	O
+strips	O
+when	O
+related	O
+to	O
+a	O
+reference	O
+potassium	B-Chemical
+response	O
+,	O
+isoprenaline	B-Chemical
+-	O
+induced	O
+relaxations	O
+were	O
+smaller	O
+in	O
+inflamed	O
+strips	O
+.	O
+
+Thus	O
+,	O
+in	O
+cystitis	B-Disease
+substantial	O
+changes	O
+of	O
+the	O
+efferent	O
+functional	O
+responses	O
+occur	O
+.	O
+
+While	O
+postjunctional	O
+beta	O
+-	O
+adrenoceptor	O
+-	O
+mediated	O
+relaxations	O
+are	O
+reduced	O
+,	O
+effects	O
+by	O
+prejunctional	O
+inhibitory	O
+muscarinic	O
+receptors	O
+may	O
+be	O
+increased	O
+.	O
+
+Direct	O
+inhibition	O
+of	O
+cardiac	O
+hyperpolarization	O
+-	O
+activated	O
+cyclic	B-Chemical
+nucleotide	I-Chemical
+-	O
+gated	O
+pacemaker	O
+channels	O
+by	O
+clonidine	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+Inhibition	O
+of	O
+cardiac	O
+sympathetic	O
+tone	O
+represents	O
+an	O
+important	O
+strategy	O
+for	O
+treatment	O
+of	O
+cardiovascular	B-Disease
+disease	I-Disease
+,	O
+including	O
+arrhythmia	B-Disease
+,	O
+coronary	B-Disease
+heart	I-Disease
+disease	I-Disease
+,	O
+and	O
+chronic	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+Activation	O
+of	O
+presynaptic	O
+alpha2	O
+-	O
+adrenoceptors	O
+is	O
+the	O
+most	O
+widely	O
+accepted	O
+mechanism	O
+of	O
+action	O
+of	O
+the	O
+antisympathetic	O
+drug	O
+clonidine	B-Chemical
+;	O
+however	O
+,	O
+other	O
+target	O
+proteins	O
+have	O
+been	O
+postulated	O
+to	O
+contribute	O
+to	O
+the	O
+in	O
+vivo	O
+actions	O
+of	O
+clonidine	B-Chemical
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+To	O
+test	O
+whether	O
+clonidine	B-Chemical
+elicits	O
+pharmacological	O
+effects	O
+independent	O
+of	O
+alpha2	O
+-	O
+adrenoceptors	O
+,	O
+we	O
+have	O
+generated	O
+mice	O
+with	O
+a	O
+targeted	O
+deletion	O
+of	O
+all	O
+3	O
+alpha2	O
+-	O
+adrenoceptor	O
+subtypes	O
+(	O
+alpha2ABC	O
+-	O
+/	O
+-	O
+)	O
+.	O
+
+Alpha2ABC	O
+-	O
+/	O
+-	O
+mice	O
+were	O
+completely	O
+unresponsive	O
+to	O
+the	O
+analgesic	O
+and	O
+hypnotic	O
+effects	O
+of	O
+clonidine	B-Chemical
+;	O
+however	O
+,	O
+clonidine	B-Chemical
+significantly	O
+lowered	O
+heart	O
+rate	O
+in	O
+alpha2ABC	O
+-	O
+/	O
+-	O
+mice	O
+by	O
+up	O
+to	O
+150	O
+bpm	O
+.	O
+
+Clonidine	B-Chemical
+-	O
+induced	O
+bradycardia	B-Disease
+in	O
+conscious	O
+alpha2ABC	O
+-	O
+/	O
+-	O
+mice	O
+was	O
+32	O
+.	O
+3	O
+%	O
+(	O
+10	O
+microg	O
+/	O
+kg	O
+)	O
+and	O
+26	O
+.	O
+6	O
+%	O
+(	O
+100	O
+microg	O
+/	O
+kg	O
+)	O
+of	O
+the	O
+effect	O
+in	O
+wild	O
+-	O
+type	O
+mice	O
+.	O
+
+A	O
+similar	O
+bradycardic	O
+effect	O
+of	O
+clonidine	B-Chemical
+was	O
+observed	O
+in	O
+isolated	O
+spontaneously	O
+beating	O
+right	O
+atria	O
+from	O
+alpha2ABC	O
+-	O
+knockout	O
+and	O
+wild	O
+-	O
+type	O
+mice	O
+.	O
+
+Clonidine	B-Chemical
+inhibited	O
+the	O
+native	O
+pacemaker	O
+current	O
+(	O
+I	O
+(	O
+f	O
+)	O
+)	O
+in	O
+isolated	O
+sinoatrial	O
+node	O
+pacemaker	O
+cells	O
+and	O
+the	O
+I	O
+(	O
+f	O
+)	O
+-	O
+generating	O
+hyperpolarization	O
+-	O
+activated	O
+cyclic	B-Chemical
+nucleotide	I-Chemical
+-	O
+gated	O
+(	O
+HCN	O
+)	O
+2	O
+and	O
+HCN4	O
+channels	O
+in	O
+transfected	O
+HEK293	O
+cells	O
+.	O
+
+As	O
+a	O
+consequence	O
+of	O
+blocking	O
+I	O
+(	O
+f	O
+)	O
+,	O
+clonidine	B-Chemical
+reduced	O
+the	O
+slope	O
+of	O
+the	O
+diastolic	O
+depolarization	O
+and	O
+the	O
+frequency	O
+of	O
+pacemaker	O
+potentials	O
+in	O
+sinoatrial	O
+node	O
+cells	O
+from	O
+wild	O
+-	O
+type	O
+and	O
+alpha2ABC	O
+-	O
+knockout	O
+mice	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Direct	O
+inhibition	O
+of	O
+cardiac	O
+HCN	O
+pacemaker	O
+channels	O
+contributes	O
+to	O
+the	O
+bradycardic	O
+effects	O
+of	O
+clonidine	B-Chemical
+gene	O
+-	O
+targeted	O
+mice	O
+in	O
+vivo	O
+,	O
+and	O
+thus	O
+,	O
+clonidine	B-Chemical
+-	O
+like	O
+drugs	O
+represent	O
+novel	O
+structures	O
+for	O
+future	O
+HCN	O
+channel	O
+inhibitors	O
+.	O
+
+Granulomatous	B-Disease
+hepatitis	I-Disease
+due	O
+to	O
+combination	B-Chemical
+of	I-Chemical
+amoxicillin	I-Chemical
+and	I-Chemical
+clavulanic	I-Chemical
+acid	I-Chemical
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+patient	O
+with	O
+amoxicillin	B-Chemical
+-	I-Chemical
+clavulanic	I-Chemical
+acid	I-Chemical
+-	O
+induced	O
+hepatitis	B-Disease
+with	O
+histologic	O
+multiple	O
+granulomas	B-Disease
+.	O
+
+This	O
+type	O
+of	O
+lesion	O
+broadens	O
+the	O
+spectrum	O
+of	O
+liver	B-Disease
+injury	I-Disease
+due	O
+to	O
+this	O
+drug	O
+combination	O
+,	O
+mainly	O
+represented	O
+by	O
+a	O
+benign	O
+cholestatic	B-Disease
+syndrome	I-Disease
+.	O
+
+The	O
+association	O
+of	O
+granulomas	B-Disease
+and	O
+eosinophilia	B-Disease
+favor	O
+an	O
+immunoallergic	O
+mechanism	O
+.	O
+
+As	O
+penicillin	B-Chemical
+derivatives	O
+and	O
+amoxicillin	B-Chemical
+alone	O
+are	O
+known	O
+to	O
+induce	O
+such	O
+types	O
+of	O
+lesions	O
+,	O
+the	O
+amoxicillin	B-Chemical
+component	O
+,	O
+with	O
+or	O
+without	O
+a	O
+potentiating	O
+effect	O
+of	O
+clavulanic	B-Chemical
+acid	I-Chemical
+,	O
+might	O
+have	O
+a	O
+major	O
+role	O
+.	O
+
+Dobutamine	B-Chemical
+stress	O
+echocardiography	O
+:	O
+a	O
+sensitive	O
+indicator	O
+of	O
+diminished	O
+myocardial	O
+function	O
+in	O
+asymptomatic	O
+doxorubicin	B-Chemical
+-	O
+treated	O
+long	O
+-	O
+term	O
+survivors	O
+of	O
+childhood	O
+cancer	B-Disease
+.	O
+
+Doxorubicin	B-Chemical
+is	O
+an	O
+effective	O
+anticancer	O
+chemotherapeutic	O
+agent	O
+known	O
+to	O
+cause	O
+acute	O
+and	O
+chronic	O
+cardiomyopathy	B-Disease
+.	O
+
+To	O
+develop	O
+a	O
+more	O
+sensitive	O
+echocardiographic	O
+screening	O
+test	O
+for	O
+cardiac	B-Disease
+damage	I-Disease
+due	O
+to	O
+doxorubicin	B-Chemical
+,	O
+a	O
+cohort	O
+study	O
+was	O
+performed	O
+using	O
+dobutamine	B-Chemical
+infusion	O
+to	O
+differentiate	O
+asymptomatic	O
+long	O
+-	O
+term	O
+survivors	O
+of	O
+childhood	O
+cancer	B-Disease
+treated	O
+with	O
+doxorubicin	B-Chemical
+from	O
+healthy	O
+control	O
+subjects	O
+.	O
+
+Echocardiographic	O
+data	O
+from	O
+the	O
+experimental	O
+group	O
+of	O
+21	O
+patients	O
+(	O
+mean	O
+age	O
+16	O
++	O
+/	O
+-	O
+5	O
+years	O
+)	O
+treated	O
+from	O
+1	O
+.	O
+6	O
+to	O
+14	O
+.	O
+3	O
+years	O
+(	O
+median	O
+5	O
+.	O
+3	O
+)	O
+before	O
+this	O
+study	O
+with	O
+27	O
+to	O
+532	O
+mg	O
+/	O
+m2	O
+of	O
+doxorubicin	B-Chemical
+(	O
+mean	O
+196	O
+)	O
+were	O
+compared	O
+with	O
+echocardiographic	O
+data	O
+from	O
+12	O
+normal	O
+age	O
+-	O
+matched	O
+control	O
+subjects	O
+.	O
+
+Graded	O
+dobutamine	B-Chemical
+infusions	O
+of	O
+0	O
+.	O
+5	O
+,	O
+2	O
+.	O
+5	O
+,	O
+5	O
+and	O
+10	O
+micrograms	O
+/	O
+kg	O
+per	O
+min	O
+were	O
+administered	O
+.	O
+
+Echocardiographic	O
+Doppler	O
+studies	O
+were	O
+performed	O
+before	O
+infusion	O
+and	O
+after	O
+15	O
+min	O
+of	O
+infusion	O
+at	O
+each	O
+rate	O
+.	O
+
+Dobutamine	B-Chemical
+infusion	O
+at	O
+10	O
+micrograms	O
+/	O
+kg	O
+per	O
+min	O
+was	O
+discontinued	O
+after	O
+six	O
+studies	O
+secondary	O
+to	O
+a	O
+50	O
+%	O
+incidence	O
+rate	O
+of	O
+adverse	O
+symptoms	O
+.	O
+
+The	O
+most	O
+important	O
+findings	O
+were	O
+that	O
+compared	O
+with	O
+values	O
+in	O
+control	O
+subjects	O
+,	O
+end	O
+-	O
+systolic	O
+left	O
+ventricular	O
+posterior	O
+wall	O
+dimension	O
+and	O
+percent	O
+of	O
+left	O
+ventricular	O
+posterior	O
+wall	O
+thickening	O
+in	O
+doxorubicin	B-Chemical
+-	O
+treated	O
+patients	O
+were	O
+decreased	O
+at	O
+baseline	O
+study	O
+and	O
+these	O
+findings	O
+were	O
+more	O
+clearly	O
+delineated	O
+with	O
+dobutamine	B-Chemical
+stimulation	O
+.	O
+
+End	O
+-	O
+systolic	O
+left	O
+ventricular	O
+posterior	O
+wall	O
+dimension	O
+at	O
+baseline	O
+for	O
+the	O
+doxorubicin	B-Chemical
+-	O
+treated	O
+group	O
+was	O
+11	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+mm	O
+versus	O
+13	O
+.	O
+1	O
++	O
+/	O
+-	O
+1	O
+.	O
+5	O
+mm	O
+for	O
+control	O
+subjects	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+End	O
+-	O
+systolic	O
+left	O
+ventricular	O
+posterior	O
+wall	O
+dimension	O
+at	O
+the	O
+5	O
+-	O
+micrograms	O
+/	O
+kg	O
+per	O
+min	O
+dobutamine	B-Chemical
+infusion	O
+for	O
+the	O
+doxorubicin	B-Chemical
+-	O
+treated	O
+group	O
+was	O
+14	O
+.	O
+1	O
++	O
+/	O
+-	O
+2	O
+.	O
+4	O
+mm	O
+versus	O
+19	O
+.	O
+3	O
++	O
+/	O
+-	O
+2	O
+.	O
+6	O
+mm	O
+for	O
+control	O
+subjects	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Influence	O
+of	O
+smoking	B-Chemical
+on	O
+developing	O
+cochlea	O
+.	O
+
+Does	O
+smoking	B-Chemical
+during	O
+pregnancy	O
+affect	O
+the	O
+amplitudes	O
+of	O
+transient	O
+evoked	O
+otoacoustic	O
+emissions	O
+in	O
+newborns	O
+?	O
+
+OBJECTIVE	O
+:	O
+Maternal	O
+tobacco	O
+smoking	B-Chemical
+has	O
+negative	O
+effects	O
+on	O
+fetal	O
+growth	O
+.	O
+
+The	O
+influence	O
+of	O
+smoking	B-Chemical
+during	O
+pregnancy	O
+on	O
+the	O
+developing	O
+cochlea	O
+has	O
+not	O
+been	O
+estimated	O
+,	O
+although	O
+smoking	B-Chemical
+has	O
+been	O
+positively	O
+associated	O
+with	O
+hearing	B-Disease
+loss	I-Disease
+in	O
+adults	O
+.	O
+
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+effects	O
+of	O
+maternal	O
+smoking	B-Chemical
+on	O
+transient	O
+evoked	O
+otoacoustic	O
+emissions	O
+(	O
+TEOAEs	O
+)	O
+of	O
+healthy	O
+neonates	O
+.	O
+
+METHODS	O
+:	O
+This	O
+study	O
+was	O
+undertaken	O
+as	O
+part	O
+of	O
+neonatal	O
+screening	O
+for	O
+hearing	B-Disease
+impairment	I-Disease
+and	O
+involved	O
+both	O
+ears	O
+of	O
+200	O
+newborns	O
+.	O
+
+Newborns	O
+whose	O
+mothers	O
+reported	O
+smoking	B-Chemical
+during	O
+pregnancy	O
+(	O
+n	O
+=	O
+200	O
+ears	O
+)	O
+were	O
+compared	O
+to	O
+a	O
+control	O
+group	O
+of	O
+newborns	O
+(	O
+n	O
+=	O
+200	O
+ears	O
+)	O
+,	O
+whose	O
+mothers	O
+were	O
+non	O
+-	O
+smokers	O
+.	O
+
+Exposure	O
+to	O
+tobacco	O
+was	O
+characterized	O
+as	O
+low	O
+(	O
+<	O
+5	O
+cigarettes	O
+per	O
+day	O
+,	O
+n	O
+=	O
+88	O
+ears	O
+)	O
+,	O
+moderate	O
+(	O
+5	O
+<	O
+or	O
+=	O
+cigarettes	O
+per	O
+day	O
+<	O
+10	O
+,	O
+n	O
+=	O
+76	O
+)	O
+or	O
+high	O
+(	O
+>	O
+or	O
+=	O
+10	O
+cigarettes	O
+per	O
+day	O
+,	O
+n	O
+=	O
+36	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+In	O
+exposed	O
+neonates	O
+,	O
+TEOAEs	O
+mean	O
+response	O
+(	O
+across	O
+frequency	O
+)	O
+and	O
+mean	O
+amplitude	O
+at	O
+4000Hz	O
+was	O
+significantly	O
+lower	O
+than	O
+in	O
+non	O
+-	O
+exposed	O
+neonates	O
+.	O
+
+Comparisons	O
+between	O
+exposed	O
+newborns	O
+'	O
+subgroups	O
+revealed	O
+no	O
+significant	O
+differences	O
+.	O
+
+However	O
+,	O
+by	O
+comparing	O
+each	O
+subgroup	O
+to	O
+control	O
+group	O
+,	O
+we	O
+found	O
+statistically	O
+significant	O
+decreases	B-Disease
+of	I-Disease
+TEOAEs	I-Disease
+amplitudes	I-Disease
+at	O
+4000Hz	O
+for	O
+all	O
+three	O
+groups	O
+.	O
+
+Mean	O
+TEOAEs	O
+responses	O
+of	O
+highly	O
+exposed	O
+newborns	O
+were	O
+also	O
+significantly	O
+lower	O
+in	O
+comparison	O
+to	O
+our	O
+control	O
+group	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+utero	O
+,	O
+exposure	O
+to	O
+tobacco	O
+smoking	B-Chemical
+seems	O
+to	O
+have	O
+a	O
+small	O
+impact	O
+on	O
+outer	O
+hair	O
+cells	O
+.	O
+
+These	O
+effects	O
+seem	O
+to	O
+be	O
+equally	O
+true	O
+for	O
+all	O
+exposed	O
+newborns	O
+,	O
+regardless	O
+of	O
+the	O
+degree	O
+of	O
+exposure	O
+.	O
+
+Further	O
+studies	O
+are	O
+needed	O
+in	O
+order	O
+to	O
+establish	O
+a	O
+potential	O
+negative	O
+effect	O
+of	O
+maternal	O
+smoking	B-Chemical
+on	O
+the	O
+neonate	O
+'	O
+s	O
+hearing	O
+acuity	O
+.	O
+
+Simvastatin	B-Chemical
+-	O
+induced	O
+bilateral	O
+leg	O
+compartment	B-Disease
+syndrome	I-Disease
+and	O
+myonecrosis	B-Disease
+associated	O
+with	O
+hypothyroidism	B-Disease
+.	O
+
+A	O
+54	O
+-	O
+year	O
+-	O
+old	O
+hypothyroid	B-Disease
+male	O
+taking	O
+thyroxine	B-Chemical
+and	O
+simvastatin	B-Chemical
+presented	O
+with	O
+bilateral	O
+leg	O
+compartment	B-Disease
+syndrome	I-Disease
+and	O
+myonecrosis	B-Disease
+.	O
+
+Urgent	O
+fasciotomies	O
+were	O
+performed	O
+and	O
+the	O
+patient	O
+made	O
+an	O
+uneventful	O
+recovery	O
+with	O
+the	O
+withdrawal	O
+of	O
+simvastatin	B-Chemical
+.	O
+
+It	O
+is	O
+likely	O
+that	O
+this	O
+complication	O
+will	O
+be	O
+seen	O
+more	O
+often	O
+with	O
+the	O
+increased	O
+worldwide	O
+use	O
+of	O
+this	O
+drug	O
+and	O
+its	O
+approval	O
+for	O
+all	O
+arteriopathic	B-Disease
+patients	O
+.	O
+
+Neuroinflammation	B-Disease
+and	O
+behavioral	B-Disease
+abnormalities	I-Disease
+after	O
+neonatal	O
+terbutaline	B-Chemical
+treatment	O
+in	O
+rats	O
+:	O
+implications	O
+for	O
+autism	B-Disease
+.	O
+
+Autism	B-Disease
+is	O
+a	O
+neurodevelopmental	B-Disease
+disorder	I-Disease
+presenting	O
+before	O
+3	O
+years	O
+of	O
+age	O
+with	O
+deficits	B-Disease
+in	I-Disease
+communication	I-Disease
+and	I-Disease
+social	I-Disease
+skills	I-Disease
+and	O
+repetitive	B-Disease
+behaviors	I-Disease
+.	O
+
+In	O
+addition	O
+to	O
+genetic	O
+influences	O
+,	O
+recent	O
+studies	O
+suggest	O
+that	O
+prenatal	O
+drug	O
+or	O
+chemical	O
+exposures	O
+are	O
+risk	O
+factors	O
+for	O
+autism	B-Disease
+.	O
+
+Terbutaline	B-Chemical
+,	O
+a	O
+beta2	O
+-	O
+adrenoceptor	O
+agonist	O
+used	O
+to	O
+arrest	O
+preterm	B-Disease
+labor	I-Disease
+,	O
+has	O
+been	O
+associated	O
+with	O
+increased	O
+concordance	O
+for	O
+autism	B-Disease
+in	O
+dizygotic	O
+twins	O
+.	O
+
+We	O
+studied	O
+the	O
+effects	O
+of	O
+terbutaline	B-Chemical
+on	O
+microglial	O
+activation	O
+in	O
+different	O
+brain	O
+regions	O
+and	O
+behavioral	O
+outcomes	O
+in	O
+developing	O
+rats	O
+.	O
+
+Newborn	O
+rats	O
+were	O
+given	O
+terbutaline	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+daily	O
+on	O
+postnatal	O
+days	O
+(	O
+PN	O
+)	O
+2	O
+to	O
+5	O
+or	O
+PN	O
+11	O
+to	O
+14	O
+and	O
+examined	O
+24	O
+h	O
+after	O
+the	O
+last	O
+dose	O
+and	O
+at	O
+PN	O
+30	O
+.	O
+
+Immunohistochemical	O
+studies	O
+showed	O
+that	O
+administration	O
+of	O
+terbutaline	B-Chemical
+on	O
+PN	O
+2	O
+to	O
+5	O
+produced	O
+a	O
+robust	O
+increase	O
+in	O
+microglial	O
+activation	O
+on	O
+PN	O
+30	O
+in	O
+the	O
+cerebral	O
+cortex	O
+,	O
+as	O
+well	O
+as	O
+in	O
+cerebellar	O
+and	O
+cerebrocortical	O
+white	O
+matter	O
+.	O
+
+None	O
+of	O
+these	O
+effects	O
+occurred	O
+in	O
+animals	O
+given	O
+terbutaline	B-Chemical
+on	O
+PN	O
+11	O
+to	O
+14	O
+.	O
+
+In	O
+behavioral	O
+tests	O
+,	O
+animals	O
+treated	O
+with	O
+terbutaline	B-Chemical
+on	O
+PN	O
+2	O
+to	O
+5	O
+showed	O
+consistent	O
+patterns	O
+of	O
+hyper	O
+-	O
+reactivity	O
+to	O
+novelty	O
+and	O
+aversive	O
+stimuli	O
+when	O
+assessed	O
+in	O
+a	O
+novel	O
+open	O
+field	O
+,	O
+as	O
+well	O
+as	O
+in	O
+the	O
+acoustic	O
+startle	O
+response	O
+test	O
+.	O
+
+Our	O
+findings	O
+indicate	O
+that	O
+beta2	O
+-	O
+adrenoceptor	O
+overstimulation	O
+during	O
+an	O
+early	O
+critical	O
+period	O
+results	O
+in	O
+microglial	O
+activation	O
+associated	O
+with	O
+innate	O
+neuroinflammatory	O
+pathways	O
+and	O
+behavioral	B-Disease
+abnormalities	I-Disease
+,	O
+similar	O
+to	O
+those	O
+described	O
+in	O
+autism	B-Disease
+.	O
+
+This	O
+study	O
+provides	O
+a	O
+useful	O
+animal	O
+model	O
+for	O
+understanding	O
+the	O
+neuropathological	O
+processes	O
+underlying	O
+autism	B-Disease
+spectrum	I-Disease
+disorders	I-Disease
+.	O
+
+Upregulation	O
+of	O
+brain	O
+expression	O
+of	O
+P	O
+-	O
+glycoprotein	O
+in	O
+MRP2	O
+-	O
+deficient	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+resembles	O
+seizure	B-Disease
+-	O
+induced	O
+up	O
+-	O
+regulation	O
+of	O
+this	O
+drug	O
+efflux	O
+transporter	O
+in	O
+normal	O
+rats	O
+.	O
+
+PURPOSE	O
+:	O
+The	O
+multidrug	O
+resistance	O
+protein	O
+2	O
+(	O
+MRP2	O
+)	O
+is	O
+a	O
+drug	O
+efflux	O
+transporter	O
+that	O
+is	O
+expressed	O
+predominantly	O
+at	O
+the	O
+apical	O
+domain	O
+of	O
+hepatocytes	O
+but	O
+seems	O
+also	O
+to	O
+be	O
+expressed	O
+at	O
+the	O
+apical	O
+membrane	O
+of	O
+brain	O
+capillary	O
+endothelial	O
+cells	O
+that	O
+form	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+(	O
+BBB	O
+)	O
+.	O
+
+MRP2	O
+is	O
+absent	O
+in	O
+the	O
+transport	O
+-	O
+deficient	O
+(	O
+TR	O
+(	O
+-	O
+)	O
+)	O
+Wistar	O
+rat	O
+mutant	O
+,	O
+so	O
+that	O
+this	O
+rat	O
+strain	O
+was	O
+very	O
+helpful	O
+in	O
+defining	O
+substrates	O
+of	O
+MRP2	O
+by	O
+comparing	O
+tissue	O
+concentrations	O
+or	O
+functional	O
+activities	O
+of	O
+compounds	O
+in	O
+MRP2	O
+-	O
+deficient	O
+rats	O
+with	O
+those	O
+in	O
+transport	O
+-	O
+competent	O
+Wistar	O
+rats	O
+.	O
+
+By	O
+using	O
+this	O
+strategy	O
+to	O
+study	O
+the	O
+involvement	O
+of	O
+MRP2	O
+in	O
+brain	O
+access	O
+of	O
+antiepileptic	O
+drugs	O
+(	O
+AEDs	O
+)	O
+,	O
+we	O
+recently	O
+reported	O
+that	O
+phenytoin	B-Chemical
+is	O
+a	O
+substrate	O
+for	O
+MRP2	O
+in	O
+the	O
+BBB	O
+.	O
+
+However	O
+,	O
+one	O
+drawback	O
+of	O
+such	O
+studies	O
+in	O
+genetically	O
+deficient	O
+rats	O
+is	O
+the	O
+fact	O
+that	O
+compensatory	O
+changes	O
+with	O
+upregulation	O
+of	O
+other	O
+transporters	O
+can	O
+occur	O
+.	O
+
+This	O
+prompted	O
+us	O
+to	O
+study	O
+the	O
+brain	O
+expression	O
+of	O
+P	O
+-	O
+glycoprotein	O
+(	O
+Pgp	O
+)	O
+,	O
+a	O
+major	O
+drug	O
+efflux	O
+transporter	O
+in	O
+many	O
+tissues	O
+,	O
+including	O
+the	O
+BBB	O
+,	O
+in	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+compared	O
+with	O
+nonmutant	O
+(	O
+wild	O
+-	O
+type	O
+)	O
+Wistar	O
+rats	O
+.	O
+
+METHODS	O
+:	O
+The	O
+expression	O
+of	O
+MRP2	O
+and	O
+Pgp	O
+in	O
+brain	O
+and	O
+liver	O
+sections	O
+of	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+and	O
+normal	O
+Wistar	O
+rats	O
+was	O
+determined	O
+with	O
+immunohistochemistry	O
+,	O
+by	O
+using	O
+a	O
+novel	O
+,	O
+highly	O
+selective	O
+monoclonal	O
+MRP2	O
+antibody	O
+and	O
+the	O
+monoclonal	O
+Pgp	O
+antibody	O
+C219	O
+,	O
+respectively	O
+.	O
+
+RESULTS	O
+:	O
+Immunofluorescence	O
+staining	O
+with	O
+the	O
+MRP2	O
+antibody	O
+was	O
+found	O
+to	O
+label	O
+a	O
+high	O
+number	O
+of	O
+microvessels	O
+throughout	O
+the	O
+brain	O
+in	O
+normal	O
+Wistar	O
+rats	O
+,	O
+whereas	O
+such	O
+labeling	O
+was	O
+absent	O
+in	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+.	O
+
+TR	O
+(	O
+-	O
+)	O
+rats	O
+exhibited	O
+a	O
+significant	O
+up	O
+-	O
+regulation	O
+of	O
+Pgp	O
+in	O
+brain	O
+capillary	O
+endothelial	O
+cells	O
+compared	O
+with	O
+wild	O
+-	O
+type	O
+controls	O
+.	O
+
+No	O
+such	O
+obvious	O
+upregulation	O
+of	O
+Pgp	O
+was	O
+observed	O
+in	O
+liver	O
+sections	O
+.	O
+
+A	O
+comparable	O
+overexpression	O
+of	O
+Pgp	O
+in	O
+the	O
+BBB	O
+was	O
+obtained	O
+after	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+in	O
+wild	O
+-	O
+type	O
+Wistar	O
+rats	O
+.	O
+
+Experiments	O
+with	O
+systemic	O
+administration	O
+of	O
+the	O
+Pgp	O
+substrate	O
+phenobarbital	B-Chemical
+and	O
+the	O
+selective	O
+Pgp	O
+inhibitor	O
+tariquidar	B-Chemical
+in	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+substantiated	O
+that	O
+Pgp	O
+is	O
+functional	O
+and	O
+compensates	O
+for	O
+the	O
+lack	O
+of	O
+MRP2	O
+in	O
+the	O
+BBB	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+data	O
+on	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+indicate	O
+that	O
+Pgp	O
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+compensation	O
+of	O
+MRP2	O
+deficiency	O
+in	O
+the	O
+BBB	O
+.	O
+
+Because	O
+such	O
+a	O
+compensatory	O
+mechanism	O
+most	O
+likely	O
+occurs	O
+to	O
+reduce	O
+injury	B-Disease
+to	I-Disease
+the	I-Disease
+brain	I-Disease
+from	O
+cytotoxic	O
+compounds	O
+,	O
+the	O
+present	O
+data	O
+substantiate	O
+the	O
+concept	O
+that	O
+MRP2	O
+performs	O
+a	O
+protective	O
+role	O
+in	O
+the	O
+BBB	O
+.	O
+
+Furthermore	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+TR	O
+(	O
+-	O
+)	O
+rats	O
+are	O
+an	O
+interesting	O
+tool	O
+to	O
+study	O
+consequences	O
+of	O
+overexpression	O
+of	O
+Pgp	O
+in	O
+the	O
+BBB	O
+on	O
+access	O
+of	O
+drugs	O
+in	O
+the	O
+brain	O
+,	O
+without	O
+the	O
+need	O
+of	O
+inducing	O
+seizures	B-Disease
+or	O
+other	O
+Pgp	O
+-	O
+enhancing	O
+events	O
+for	O
+this	O
+purpose	O
+.	O
+
+Role	O
+of	O
+xanthine	B-Chemical
+oxidase	O
+in	O
+dexamethasone	B-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+in	O
+rats	O
+.	O
+
+1	O
+.	O
+
+Glucocorticoid	O
+-	O
+induced	O
+hypertension	B-Disease
+(	O
+GC	O
+-	O
+HT	B-Disease
+)	O
+in	O
+the	O
+rat	O
+is	O
+associated	O
+with	O
+nitric	B-Chemical
+oxide	I-Chemical
+-	O
+redox	O
+imbalance	O
+.	O
+
+2	O
+.	O
+
+We	O
+studied	O
+the	O
+role	O
+of	O
+xanthine	B-Chemical
+oxidase	O
+(	O
+XO	O
+)	O
+,	O
+which	O
+is	O
+implicated	O
+in	O
+the	O
+production	O
+of	O
+reactive	O
+oxygen	O
+species	O
+,	O
+in	O
+dexamethasone	B-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+(	O
+dex	B-Chemical
+-	O
+HT	B-Disease
+)	O
+.	O
+
+3	O
+.	O
+
+Thirty	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+were	O
+divided	O
+randomly	O
+into	O
+four	O
+treatment	O
+groups	O
+:	O
+saline	O
+,	O
+dexamethasone	B-Chemical
+(	O
+dex	B-Chemical
+)	O
+,	O
+allopurinol	B-Chemical
+plus	O
+saline	O
+,	O
+and	O
+allopurinol	B-Chemical
+plus	O
+dex	B-Chemical
+.	O
+
+4	O
+.	O
+
+Systolic	O
+blood	O
+pressures	O
+(	O
+SBP	O
+)	O
+and	O
+bodyweights	O
+were	O
+recorded	O
+each	O
+alternate	O
+day	O
+.	O
+
+Thymus	O
+weight	O
+was	O
+used	O
+as	O
+a	O
+marker	O
+of	O
+glucocorticoid	O
+activity	O
+,	O
+and	O
+serum	O
+urate	B-Chemical
+to	O
+assess	O
+XO	O
+inhibition	O
+.	O
+
+5	O
+.	O
+
+Dex	B-Chemical
+increased	B-Disease
+SBP	I-Disease
+(	O
+110	O
++	O
+/	O
+-	O
+2	O
+-	O
+126	O
++	O
+/	O
+-	O
+3	O
+mmHg	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+decreased	B-Disease
+thymus	I-Disease
+(	I-Disease
+P	I-Disease
+<	I-Disease
+0	I-Disease
+.	I-Disease
+001	I-Disease
+)	I-Disease
+and	I-Disease
+bodyweights	I-Disease
+(	O
+P	O
+"	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Allopurinol	B-Chemical
+decreased	O
+serum	O
+urate	B-Chemical
+from	O
+76	O
++	O
+/	O
+-	O
+5	O
+to	O
+30	O
++	O
+/	O
+-	O
+3	O
+micromol	O
+/	O
+L	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+saline	O
+and	O
+from	O
+84	O
++	O
+/	O
+-	O
+13	O
+to	O
+28	O
++	O
+/	O
+-	O
+2	O
+micromol	O
+/	O
+L	O
+in	O
+dex	B-Chemical
+-	O
+treated	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+groups	O
+.	O
+
+6	O
+.	O
+
+Allopurinol	B-Chemical
+did	O
+not	O
+prevent	O
+dex	B-Chemical
+-	O
+HT	B-Disease
+.	O
+
+This	O
+,	O
+together	O
+with	O
+our	O
+previous	O
+findings	O
+that	O
+allopurinol	B-Chemical
+failed	O
+to	O
+prevent	O
+adrenocorticotrophic	O
+hormone	O
+induced	O
+hypertension	B-Disease
+,	O
+suggests	O
+that	O
+XO	O
+activity	O
+is	O
+not	O
+a	O
+major	O
+determinant	O
+of	O
+GC	O
+-	O
+HT	B-Disease
+in	O
+the	O
+rat	O
+.	O
+
+Side	O
+effects	O
+of	O
+postoperative	O
+administration	O
+of	O
+methylprednisolone	B-Chemical
+and	O
+gentamicin	B-Chemical
+into	O
+the	O
+posterior	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+space	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+assess	O
+the	O
+incidence	O
+of	O
+postoperative	O
+emetic	O
+side	O
+effects	O
+after	O
+the	O
+administration	O
+of	O
+methylprednisolone	B-Chemical
+and	O
+gentamicin	B-Chemical
+into	O
+the	O
+posterior	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+space	O
+at	O
+the	O
+end	O
+of	O
+routine	O
+cataract	B-Disease
+surgery	O
+.	O
+
+SETTING	O
+:	O
+St	O
+.	O
+
+Luke	O
+'	O
+s	O
+Hospital	O
+,	O
+Gwardamangia	O
+,	O
+Malta	O
+.	O
+
+METHODS	O
+:	O
+A	O
+double	O
+-	O
+blind	O
+double	O
+-	O
+armed	O
+prospective	O
+study	O
+comprised	O
+40	O
+patients	O
+who	O
+had	O
+uneventful	O
+sutureless	O
+phacoemulsification	O
+under	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+local	O
+infiltration	O
+of	O
+3	O
+mL	O
+of	O
+plain	O
+lignocaine	B-Chemical
+.	O
+
+At	O
+the	O
+end	O
+of	O
+the	O
+procedure	O
+,	O
+Group	O
+A	O
+(	O
+n	O
+=	O
+20	O
+)	O
+had	O
+20	O
+mg	O
+/	O
+0	O
+.	O
+5	O
+mL	O
+of	O
+methylprednisolone	B-Chemical
+and	O
+10	O
+mg	O
+/	O
+0	O
+.	O
+5	O
+mL	O
+of	O
+gentamicin	B-Chemical
+injected	O
+into	O
+the	O
+posterior	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+space	O
+and	O
+Group	O
+B	O
+(	O
+n	O
+=	O
+20	O
+)	O
+had	O
+the	O
+same	O
+combination	O
+injected	O
+into	O
+the	O
+anterior	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+space	O
+.	O
+
+Postoperatively	O
+,	O
+all	O
+patients	O
+were	O
+assessed	O
+for	O
+symptoms	O
+of	O
+nausea	B-Disease
+,	I-Disease
+vomiting	I-Disease
+,	O
+and	O
+headache	B-Disease
+.	O
+
+A	O
+chi	O
+-	O
+square	O
+test	O
+was	O
+used	O
+to	O
+assess	O
+the	O
+statistical	O
+significance	O
+of	O
+results	O
+.	O
+
+RESULTS	O
+:	O
+Sixty	O
+percent	O
+in	O
+Group	O
+A	O
+developed	O
+postoperative	B-Disease
+emetic	I-Disease
+symptoms	I-Disease
+,	O
+headache	B-Disease
+,	O
+or	O
+both	O
+;	O
+1	O
+patient	O
+in	O
+Group	O
+B	O
+developed	O
+symptoms	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+administration	O
+of	O
+methylprednisolone	B-Chemical
+and	O
+gentamicin	B-Chemical
+in	O
+the	O
+posterior	O
+sub	O
+-	O
+Tenon	O
+'	O
+s	O
+space	O
+was	O
+related	O
+to	O
+a	O
+high	O
+incidence	O
+of	O
+side	O
+effects	O
+including	O
+nausea	B-Disease
+,	I-Disease
+vomiting	I-Disease
+,	O
+and	O
+headache	B-Disease
+.	O
+
+All	O
+adverse	O
+effects	O
+were	O
+self	O
+-	O
+limiting	O
+.	O
+
+Assessment	O
+of	O
+a	O
+new	O
+non	O
+-	O
+invasive	O
+index	O
+of	O
+cardiac	O
+performance	O
+for	O
+detection	O
+of	O
+dobutamine	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+ischemia	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Electrocardiography	O
+has	O
+a	O
+very	O
+low	O
+sensitivity	O
+in	O
+detecting	O
+dobutamine	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+ischemia	I-Disease
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+assess	O
+the	O
+added	O
+diagnostic	O
+value	O
+of	O
+a	O
+new	O
+cardiac	O
+performance	O
+index	O
+(	O
+dP	O
+/	O
+dtejc	O
+)	O
+measurement	O
+,	O
+based	O
+on	O
+brachial	O
+artery	O
+flow	O
+changes	O
+,	O
+as	O
+compared	O
+to	O
+standard	O
+12	O
+-	O
+lead	O
+ECG	O
+,	O
+for	O
+detecting	O
+dobutamine	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+ischemia	I-Disease
+,	O
+using	O
+Tc99m	B-Chemical
+-	I-Chemical
+Sestamibi	I-Chemical
+single	O
+-	O
+photon	O
+emission	O
+computed	O
+tomography	O
+as	O
+the	O
+gold	O
+standard	O
+of	O
+comparison	O
+to	O
+assess	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+ischemia	B-Disease
+.	O
+
+METHODS	O
+:	O
+The	O
+study	O
+group	O
+comprised	O
+40	O
+patients	O
+undergoing	O
+Sestamibi	B-Chemical
+-	O
+SPECT	O
+/	O
+dobutamine	B-Chemical
+stress	O
+test	O
+.	O
+
+Simultaneous	O
+measurements	O
+of	O
+ECG	O
+and	O
+brachial	O
+artery	O
+dP	O
+/	O
+dtejc	O
+were	O
+performed	O
+at	O
+each	O
+dobutamine	B-Chemical
+level	O
+.	O
+
+In	O
+19	O
+of	O
+the	O
+40	O
+patients	O
+perfusion	O
+defects	O
+compatible	O
+with	O
+ischemia	B-Disease
+were	O
+detected	O
+on	O
+SPECT	O
+.	O
+
+The	O
+increase	O
+in	O
+dP	O
+/	O
+dtejc	O
+during	O
+infusion	O
+of	O
+dobutamine	B-Chemical
+in	O
+this	O
+group	O
+was	O
+severely	O
+impaired	O
+as	O
+compared	O
+to	O
+the	O
+non	O
+-	O
+ischemic	O
+group	O
+.	O
+
+dP	O
+/	O
+dtejc	O
+outcome	O
+was	O
+combined	O
+with	O
+the	O
+ECG	O
+results	O
+,	O
+giving	O
+an	O
+ECG	O
+-	O
+enhanced	O
+value	O
+,	O
+and	O
+compared	O
+to	O
+ECG	O
+alone	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+sensitivity	O
+improved	O
+dramatically	O
+from	O
+16	O
+%	O
+to	O
+79	O
+%	O
+,	O
+positive	O
+predictive	O
+value	O
+increased	O
+from	O
+60	O
+%	O
+to	O
+68	O
+%	O
+and	O
+negative	O
+predictive	O
+value	O
+from	O
+54	O
+%	O
+to	O
+78	O
+%	O
+,	O
+and	O
+specificity	O
+decreased	O
+from	O
+90	O
+%	O
+to	O
+67	O
+%	O
+.	O
+
+CONCLUSIONS	O
+:	O
+If	O
+ECG	O
+alone	O
+is	O
+used	O
+for	O
+specificity	O
+,	O
+the	O
+combination	O
+with	O
+dP	O
+/	O
+dtejc	O
+improved	O
+the	O
+sensitivity	O
+of	O
+the	O
+test	O
+and	O
+could	O
+be	O
+a	O
+cost	O
+-	O
+savings	O
+alternative	O
+to	O
+cardiac	O
+imaging	O
+or	O
+perfusion	O
+studies	O
+to	O
+detect	O
+myocardial	B-Disease
+ischemia	I-Disease
+,	O
+especially	O
+in	O
+patients	O
+unable	O
+to	O
+exercise	O
+.	O
+
+Cocaine	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+:	O
+clinical	O
+observations	O
+and	O
+pathogenetic	O
+considerations	O
+.	O
+
+Clinical	O
+and	O
+experimental	O
+data	O
+published	O
+to	O
+date	O
+suggest	O
+several	O
+possible	O
+mechanisms	O
+by	O
+which	O
+cocaine	B-Chemical
+may	O
+result	O
+in	O
+acute	B-Disease
+myocardial	I-Disease
+infarction	I-Disease
+.	O
+
+In	O
+individuals	O
+with	O
+preexisting	O
+,	O
+high	O
+-	O
+grade	O
+coronary	O
+arterial	O
+narrowing	O
+,	O
+acute	B-Disease
+myocardial	I-Disease
+infarction	I-Disease
+may	O
+result	O
+from	O
+an	O
+increase	O
+in	O
+myocardial	O
+oxygen	B-Chemical
+demand	O
+associated	O
+with	O
+cocaine	B-Chemical
+-	O
+induced	O
+increase	O
+in	O
+rate	O
+-	O
+pressure	O
+product	O
+.	O
+
+In	O
+other	O
+individuals	O
+with	O
+no	O
+underlying	O
+atherosclerotic	B-Disease
+obstruction	I-Disease
+,	O
+coronary	B-Disease
+occlusion	I-Disease
+may	O
+be	O
+due	O
+to	O
+spasm	B-Disease
+,	O
+thrombus	B-Disease
+,	O
+or	O
+both	O
+.	O
+
+With	O
+regard	O
+to	O
+spasm	B-Disease
+,	O
+the	O
+clinical	O
+findings	O
+are	O
+largely	O
+circumstantial	O
+,	O
+and	O
+the	O
+locus	O
+of	O
+cocaine	B-Chemical
+-	O
+induced	O
+vasoconstriction	O
+remains	O
+speculative	O
+.	O
+
+Although	O
+certain	O
+clinical	O
+and	O
+experimental	O
+findings	O
+support	O
+the	O
+hypothesis	O
+that	O
+spasm	B-Disease
+involves	O
+the	O
+epicardial	O
+,	O
+medium	O
+-	O
+size	O
+vessels	O
+,	O
+other	O
+data	O
+suggest	O
+intramural	O
+vasoconstriction	O
+.	O
+
+Diffuse	O
+intramural	O
+vasoconstriction	O
+is	O
+not	O
+consistent	O
+with	O
+reports	O
+of	O
+segmental	O
+,	O
+discrete	O
+infarction	B-Disease
+.	O
+
+Whereas	O
+certain	O
+in	O
+vivo	O
+data	O
+suggest	O
+that	O
+these	O
+effects	O
+are	O
+alpha	O
+-	O
+mediated	O
+,	O
+other	O
+in	O
+vitro	O
+data	O
+suggest	O
+the	O
+opposite	O
+.	O
+
+The	O
+finding	O
+of	O
+cocaine	B-Chemical
+-	O
+induced	O
+vasoconstriction	O
+in	O
+segments	O
+of	O
+(	O
+noninnervated	O
+)	O
+human	O
+umbilical	O
+artery	O
+suggests	O
+that	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+intact	O
+innervation	O
+is	O
+not	O
+sufficient	O
+to	O
+explain	O
+the	O
+discrepant	O
+data	O
+involving	O
+the	O
+possibility	O
+of	O
+alpha	O
+-	O
+mediated	O
+effects	O
+.	O
+
+Finally	O
+,	O
+the	O
+contribution	O
+of	O
+a	O
+primary	O
+,	O
+thrombotic	B-Disease
+effect	O
+of	O
+cocaine	B-Chemical
+has	O
+not	O
+been	O
+excluded	O
+.	O
+
+Proteomic	O
+analysis	O
+of	O
+striatal	O
+proteins	O
+in	O
+the	O
+rat	O
+model	O
+of	O
+L	B-Chemical
+-	I-Chemical
+DOPA	I-Chemical
+-	O
+induced	O
+dyskinesia	B-Disease
+.	O
+
+L	B-Chemical
+-	I-Chemical
+DOPA	I-Chemical
+-	O
+induced	O
+dyskinesia	B-Disease
+(	O
+LID	B-Disease
+)	O
+is	O
+among	O
+the	O
+motor	O
+complications	O
+that	O
+arise	O
+in	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+patients	O
+after	O
+a	O
+prolonged	O
+treatment	O
+with	O
+L	B-Chemical
+-	I-Chemical
+DOPA	I-Chemical
+.	O
+
+To	O
+this	O
+day	O
+,	O
+transcriptome	O
+analysis	O
+has	O
+been	O
+performed	O
+in	O
+a	O
+rat	O
+model	O
+of	O
+LID	B-Disease
+[	O
+Neurobiol	O
+.	O
+Dis	O
+.	O
+,	O
+17	O
+(	O
+2004	O
+)	O
+,	O
+219	O
+]	O
+but	O
+information	O
+regarding	O
+the	O
+proteome	O
+is	O
+still	O
+lacking	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+investigated	O
+the	O
+changes	O
+occurring	O
+at	O
+the	O
+protein	O
+level	O
+in	O
+striatal	O
+samples	O
+obtained	O
+from	O
+the	O
+unilaterally	O
+6	B-Chemical
+-	I-Chemical
+hydroxydopamine	I-Chemical
+-	O
+lesion	O
+rat	O
+model	O
+of	O
+PD	B-Disease
+treated	O
+with	O
+saline	O
+,	O
+L	B-Chemical
+-	I-Chemical
+DOPA	I-Chemical
+or	O
+bromocriptine	B-Chemical
+using	O
+two	O
+-	O
+dimensional	O
+difference	O
+gel	O
+electrophoresis	O
+and	O
+mass	O
+spectrometry	O
+(	O
+MS	O
+)	O
+.	O
+
+Rats	O
+treated	O
+with	O
+L	B-Chemical
+-	I-Chemical
+DOPA	I-Chemical
+were	O
+allocated	O
+to	O
+two	O
+groups	O
+based	O
+on	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+LID	B-Disease
+.	O
+
+Among	O
+the	O
+2000	O
+spots	O
+compared	O
+for	O
+statistical	O
+difference	O
+,	O
+67	O
+spots	O
+were	O
+significantly	O
+changed	O
+in	O
+abundance	O
+and	O
+identified	O
+using	O
+matrix	O
+-	O
+assisted	O
+laser	O
+desorption	O
+/	O
+ionization	O
+time	O
+-	O
+of	O
+-	O
+flight	O
+MS	O
+,	O
+atmospheric	O
+pressure	O
+matrix	O
+-	O
+assisted	O
+laser	O
+desorption	O
+/	O
+ionization	O
+and	O
+HPLC	O
+coupled	O
+tandem	O
+MS	O
+(	O
+LC	O
+/	O
+MS	O
+/	O
+MS	O
+)	O
+.	O
+
+Out	O
+of	O
+these	O
+67	O
+proteins	O
+,	O
+LID	B-Disease
+significantly	O
+changed	O
+the	O
+expression	O
+level	O
+of	O
+five	O
+proteins	O
+:	O
+alphabeta	O
+-	O
+crystalin	O
+,	O
+gamma	O
+-	O
+enolase	O
+,	O
+guanidoacetate	O
+methyltransferase	O
+,	O
+vinculin	O
+,	O
+and	O
+proteasome	O
+alpha	O
+-	O
+2	O
+subunit	O
+.	O
+
+Complementary	O
+techniques	O
+such	O
+as	O
+western	O
+immunoblotting	O
+and	O
+immunohistochemistry	O
+were	O
+performed	O
+to	O
+investigate	O
+the	O
+validity	O
+of	O
+the	O
+data	O
+obtained	O
+using	O
+the	O
+proteomic	O
+approach	O
+.	O
+
+In	O
+conclusion	O
+,	O
+this	O
+study	O
+provides	O
+new	O
+insights	O
+into	O
+the	O
+protein	O
+changes	O
+occurring	O
+in	O
+LID	B-Disease
+.	O
+
+Cardiac	O
+Angiography	O
+in	O
+Renally	O
+Impaired	O
+Patients	O
+(	O
+CARE	O
+)	O
+study	O
+:	O
+a	O
+randomized	O
+double	O
+-	O
+blind	O
+trial	O
+of	O
+contrast	O
+-	O
+induced	O
+nephropathy	B-Disease
+in	O
+patients	O
+with	O
+chronic	B-Disease
+kidney	I-Disease
+disease	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+No	O
+direct	O
+comparisons	O
+exist	O
+of	O
+the	O
+renal	O
+tolerability	O
+of	O
+the	O
+low	O
+-	O
+osmolality	O
+contrast	B-Chemical
+medium	I-Chemical
+iopamidol	B-Chemical
+with	O
+that	O
+of	O
+the	O
+iso	O
+-	O
+osmolality	O
+contrast	B-Chemical
+medium	I-Chemical
+iodixanol	B-Chemical
+in	O
+high	O
+-	O
+risk	O
+patients	O
+.	O
+
+METHODS	O
+AND	O
+RESULTS	O
+:	O
+The	O
+present	O
+study	O
+is	O
+a	O
+multicenter	O
+,	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+comparison	O
+of	O
+iopamidol	B-Chemical
+and	O
+iodixanol	B-Chemical
+in	O
+patients	O
+with	O
+chronic	B-Disease
+kidney	I-Disease
+disease	I-Disease
+(	O
+estimated	O
+glomerular	O
+filtration	O
+rate	O
+,	O
+20	O
+to	O
+59	O
+mL	O
+/	O
+min	O
+)	O
+who	O
+underwent	O
+cardiac	O
+angiography	O
+or	O
+percutaneous	O
+coronary	O
+interventions	O
+.	O
+
+Serum	O
+creatinine	B-Chemical
+(	O
+SCr	O
+)	O
+levels	O
+and	O
+estimated	O
+glomerular	O
+filtration	O
+rate	O
+were	O
+assessed	O
+at	O
+baseline	O
+and	O
+2	O
+to	O
+5	O
+days	O
+after	O
+receiving	O
+medications	O
+.	O
+
+The	O
+primary	O
+outcome	O
+was	O
+a	O
+postdose	O
+SCr	O
+increase	O
+>	O
+or	O
+=	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+dL	O
+(	O
+44	O
+.	O
+2	O
+micromol	O
+/	O
+L	O
+)	O
+over	O
+baseline	O
+.	O
+
+Secondary	O
+outcomes	O
+were	O
+a	O
+postdose	O
+SCr	O
+increase	O
+>	O
+or	O
+=	O
+25	O
+%	O
+,	O
+a	O
+postdose	O
+estimated	O
+glomerular	O
+filtration	O
+rate	O
+decrease	O
+of	O
+>	O
+or	O
+=	O
+25	O
+%	O
+,	O
+and	O
+the	O
+mean	O
+peak	O
+change	O
+in	O
+SCr	O
+.	O
+
+In	O
+414	O
+patients	O
+,	O
+contrast	O
+volume	O
+,	O
+presence	O
+of	O
+diabetes	B-Disease
+mellitus	I-Disease
+,	O
+use	O
+of	O
+N	B-Chemical
+-	I-Chemical
+acetylcysteine	I-Chemical
+,	O
+mean	O
+baseline	O
+SCr	O
+,	O
+and	O
+estimated	O
+glomerular	O
+filtration	O
+rate	O
+were	O
+comparable	O
+in	O
+the	O
+2	O
+groups	O
+.	O
+
+SCr	O
+increases	O
+>	O
+or	O
+=	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+dL	O
+occurred	O
+in	O
+4	O
+.	O
+4	O
+%	O
+(	O
+9	O
+of	O
+204	O
+patients	O
+)	O
+after	O
+iopamidol	B-Chemical
+and	O
+6	O
+.	O
+7	O
+%	O
+(	O
+14	O
+of	O
+210	O
+patients	O
+)	O
+after	O
+iodixanol	B-Chemical
+(	O
+P	O
+=	O
+0	O
+.	O
+39	O
+)	O
+,	O
+whereas	O
+rates	O
+of	O
+SCr	O
+increases	O
+>	O
+or	O
+=	O
+25	O
+%	O
+were	O
+9	O
+.	O
+8	O
+%	O
+and	O
+12	O
+.	O
+4	O
+%	O
+,	O
+respectively	O
+(	O
+P	O
+=	O
+0	O
+.	O
+44	O
+)	O
+.	O
+
+In	O
+patients	O
+with	O
+diabetes	B-Disease
+,	O
+SCr	O
+increases	O
+>	O
+or	O
+=	O
+0	O
+.	O
+5	O
+mg	O
+/	O
+dL	O
+were	O
+5	O
+.	O
+1	O
+%	O
+(	O
+4	O
+of	O
+78	O
+patients	O
+)	O
+with	O
+iopamidol	B-Chemical
+and	O
+13	O
+.	O
+0	O
+%	O
+(	O
+12	O
+of	O
+92	O
+patients	O
+)	O
+with	O
+iodixanol	B-Chemical
+(	O
+P	O
+=	O
+0	O
+.	O
+11	O
+)	O
+,	O
+whereas	O
+SCr	O
+increases	O
+>	O
+or	O
+=	O
+25	O
+%	O
+were	O
+10	O
+.	O
+3	O
+%	O
+and	O
+15	O
+.	O
+2	O
+%	O
+,	O
+respectively	O
+(	O
+P	O
+=	O
+0	O
+.	O
+37	O
+)	O
+.	O
+
+Mean	O
+post	O
+-	O
+SCr	O
+increases	O
+were	O
+significantly	O
+less	O
+with	O
+iopamidol	B-Chemical
+(	O
+all	O
+patients	O
+:	O
+0	O
+.	O
+07	O
+versus	O
+0	O
+.	O
+12	O
+mg	O
+/	O
+dL	O
+,	O
+6	O
+.	O
+2	O
+versus	O
+10	O
+.	O
+6	O
+micromol	O
+/	O
+L	O
+,	O
+P	O
+=	O
+0	O
+.	O
+03	O
+;	O
+patients	O
+with	O
+diabetes	B-Disease
+:	O
+0	O
+.	O
+07	O
+versus	O
+0	O
+.	O
+16	O
+mg	O
+/	O
+dL	O
+,	O
+6	O
+.	O
+2	O
+versus	O
+14	O
+.	O
+1	O
+micromol	O
+/	O
+L	O
+,	O
+P	O
+=	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+rate	O
+of	O
+contrast	O
+-	O
+induced	O
+nephropathy	B-Disease
+,	O
+defined	O
+by	O
+multiple	O
+end	O
+points	O
+,	O
+is	O
+not	O
+statistically	O
+different	O
+after	O
+the	O
+intraarterial	O
+administration	O
+of	O
+iopamidol	B-Chemical
+or	O
+iodixanol	B-Chemical
+to	O
+high	O
+-	O
+risk	O
+patients	O
+,	O
+with	O
+or	O
+without	O
+diabetes	B-Disease
+mellitus	I-Disease
+.	O
+
+Any	O
+true	O
+difference	O
+between	O
+the	O
+agents	O
+is	O
+small	O
+and	O
+not	O
+likely	O
+to	O
+be	O
+clinically	O
+significant	O
+.	O
+
+A	O
+novel	O
+compound	O
+,	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+,	O
+attenuates	O
+cognitive	B-Disease
+deficits	I-Disease
+and	O
+shows	O
+neuroprotective	O
+effects	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+dementia	B-Disease
+models	O
+.	O
+
+To	O
+develop	O
+a	O
+novel	O
+and	O
+effective	O
+drug	O
+that	O
+could	O
+enhance	O
+cognitive	O
+function	O
+and	O
+neuroprotection	O
+,	O
+we	O
+newly	O
+synthesized	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+by	O
+the	O
+esterification	O
+of	O
+maltol	B-Chemical
+and	O
+p	B-Chemical
+-	I-Chemical
+coumaric	I-Chemical
+acid	I-Chemical
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+investigated	O
+whether	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+could	O
+improve	O
+cognitive	B-Disease
+decline	I-Disease
+in	O
+scopolamine	B-Chemical
+-	O
+injected	O
+rats	O
+and	O
+in	O
+amyloid	B-Chemical
+beta	I-Chemical
+peptide	I-Chemical
+(	I-Chemical
+1	I-Chemical
+-	I-Chemical
+42	I-Chemical
+)	I-Chemical
+-	O
+infused	O
+rats	O
+.	O
+
+Maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+was	O
+found	O
+to	O
+attenuate	O
+cognitive	B-Disease
+deficits	I-Disease
+in	O
+both	O
+rat	O
+models	O
+using	O
+passive	O
+avoidance	O
+test	O
+and	O
+to	O
+reduce	O
+apoptotic	O
+cell	O
+death	O
+observed	O
+in	O
+the	O
+hippocampus	O
+of	O
+the	O
+amyloid	B-Chemical
+beta	I-Chemical
+peptide	I-Chemical
+(	I-Chemical
+1	I-Chemical
+-	I-Chemical
+42	I-Chemical
+)	I-Chemical
+-	O
+infused	O
+rats	O
+.	O
+
+We	O
+also	O
+examined	O
+the	O
+neuroprotective	O
+effects	O
+of	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+in	O
+vitro	O
+using	O
+SH	O
+-	O
+SY5Y	O
+cells	O
+.	O
+
+Cells	O
+were	O
+pretreated	O
+with	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+,	O
+before	O
+exposed	O
+to	O
+amyloid	B-Chemical
+beta	I-Chemical
+peptide	I-Chemical
+(	I-Chemical
+1	I-Chemical
+-	I-Chemical
+42	I-Chemical
+)	I-Chemical
+,	O
+glutamate	B-Chemical
+or	O
+H2O2	B-Chemical
+.	O
+
+We	O
+found	O
+that	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+significantly	O
+decreased	O
+apoptotic	O
+cell	O
+death	O
+and	O
+reduced	O
+reactive	O
+oxygen	O
+species	O
+,	O
+cytochrome	O
+c	O
+release	O
+,	O
+and	O
+caspase	O
+3	O
+activation	O
+.	O
+
+Taking	O
+these	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+results	O
+together	O
+,	O
+our	O
+study	O
+suggests	O
+that	O
+maltolyl	B-Chemical
+p	I-Chemical
+-	I-Chemical
+coumarate	I-Chemical
+is	O
+a	O
+potentially	O
+effective	O
+candidate	O
+against	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+that	O
+is	O
+characterized	O
+by	O
+wide	O
+spread	O
+neuronal	B-Disease
+death	I-Disease
+and	O
+progressive	O
+decline	B-Disease
+of	I-Disease
+cognitive	I-Disease
+function	I-Disease
+.	O
+
+Attenuation	O
+of	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+nigrostriatal	O
+dopaminergic	O
+neurotoxicity	B-Disease
+in	O
+mice	O
+by	O
+lipopolysaccharide	B-Chemical
+pretreatment	O
+.	O
+
+Immunological	O
+activation	O
+has	O
+been	O
+proposed	O
+to	O
+play	O
+a	O
+role	O
+in	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+dopaminergic	B-Disease
+terminal	I-Disease
+damage	I-Disease
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+examined	O
+the	O
+roles	O
+of	O
+lipopolysaccharide	B-Chemical
+,	O
+a	O
+pro	O
+-	O
+inflammatory	O
+and	O
+inflammatory	O
+factor	O
+,	O
+treatment	O
+in	O
+modulating	O
+the	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+nigrostriatal	O
+dopamine	B-Chemical
+neurotoxicity	B-Disease
+.	O
+
+Lipopolysaccharide	B-Chemical
+pretreatment	O
+did	O
+not	O
+affect	O
+the	O
+basal	O
+body	O
+temperature	O
+or	O
+methamphetamine	B-Chemical
+-	O
+elicited	O
+hyperthermia	B-Disease
+three	O
+days	O
+later	O
+.	O
+
+Such	O
+systemic	O
+lipopolysaccharide	B-Chemical
+treatment	O
+mitigated	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+striatal	O
+dopamine	B-Chemical
+and	O
+3	B-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dihydroxyphenylacetic	I-Chemical
+acid	I-Chemical
+depletions	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+.	O
+
+As	O
+the	O
+most	O
+potent	O
+dose	O
+(	O
+1	O
+mg	O
+/	O
+kg	O
+)	O
+of	O
+lipopolysaccharide	B-Chemical
+was	O
+administered	O
+two	O
+weeks	O
+,	O
+one	O
+day	O
+before	O
+or	O
+after	O
+the	O
+methamphetamine	B-Chemical
+dosing	O
+regimen	O
+,	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+striatal	O
+dopamine	B-Chemical
+and	O
+3	B-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dihydroxyphenylacetic	I-Chemical
+acid	I-Chemical
+depletions	O
+remained	O
+unaltered	O
+.	O
+
+Moreover	O
+,	O
+systemic	O
+lipopolysaccharide	B-Chemical
+pretreatment	O
+(	O
+1	O
+mg	O
+/	O
+kg	O
+)	O
+attenuated	O
+local	O
+methamphetamine	B-Chemical
+infusion	O
+-	O
+produced	O
+dopamine	B-Chemical
+and	O
+3	B-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dihydroxyphenylacetic	I-Chemical
+acid	I-Chemical
+depletions	O
+in	O
+the	O
+striatum	O
+,	O
+indicating	O
+that	O
+the	O
+protective	O
+effect	O
+of	O
+lipopolysaccharide	B-Chemical
+is	O
+less	O
+likely	O
+due	O
+to	O
+interrupted	O
+peripheral	O
+distribution	O
+or	O
+metabolism	O
+of	O
+methamphetamine	B-Chemical
+.	O
+
+We	O
+concluded	O
+a	O
+critical	O
+time	O
+window	O
+for	O
+systemic	O
+lipopolysaccharide	B-Chemical
+pretreatment	O
+in	O
+exerting	O
+effective	O
+protection	O
+against	O
+methamphetamine	B-Chemical
+-	O
+induced	O
+nigrostriatal	O
+dopamine	B-Chemical
+neurotoxicity	B-Disease
+.	O
+
+Acute	O
+myocarditis	B-Disease
+associated	O
+with	O
+clozapine	B-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+A	O
+case	O
+of	O
+acute	O
+myocarditis	B-Disease
+associated	O
+with	O
+the	O
+commencement	O
+of	O
+clozapine	B-Chemical
+is	O
+described	O
+,	O
+highlighting	O
+the	O
+onset	O
+,	O
+course	O
+and	O
+possible	O
+contributing	O
+factors	O
+.	O
+
+There	O
+is	O
+an	O
+urgent	O
+need	O
+to	O
+raise	O
+awareness	O
+about	O
+this	O
+potentially	O
+fatal	O
+complication	O
+of	O
+clozapine	B-Chemical
+use	O
+.	O
+
+RESULTS	O
+:	O
+A	O
+20	O
+-	O
+year	O
+-	O
+old	O
+male	O
+with	O
+schizophrenia	B-Disease
+developed	O
+a	O
+sudden	O
+onset	O
+of	O
+myocarditis	B-Disease
+after	O
+commencement	O
+of	O
+clozapine	B-Chemical
+.	O
+
+The	O
+patient	O
+recovered	O
+with	O
+intensive	O
+medical	O
+support	O
+.	O
+
+The	O
+symptoms	O
+occurred	O
+around	O
+2	O
+weeks	O
+after	O
+starting	O
+clozapine	B-Chemical
+in	O
+an	O
+inpatient	O
+setting	O
+.	O
+
+Possible	O
+contributing	O
+factors	O
+may	O
+have	O
+been	O
+concomitant	O
+antidepressant	B-Chemical
+use	O
+and	O
+unaccustomed	O
+physical	O
+activity	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Myocarditis	B-Disease
+is	O
+an	O
+increasingly	O
+recognized	O
+complication	O
+associated	O
+with	O
+the	O
+use	O
+of	O
+clozapine	B-Chemical
+.	O
+
+It	O
+can	O
+be	O
+fatal	O
+if	O
+not	O
+recognized	O
+and	O
+treated	O
+early	O
+.	O
+
+Considering	O
+that	O
+clozapine	B-Chemical
+remains	O
+the	O
+gold	O
+standard	O
+in	O
+treatment	O
+of	O
+resistant	O
+psychosis	B-Disease
+,	O
+there	O
+is	O
+an	O
+urgent	O
+need	O
+to	O
+raise	O
+awareness	O
+among	O
+medical	O
+and	O
+paramedical	O
+staff	O
+involved	O
+in	O
+the	O
+care	O
+of	O
+these	O
+patients	O
+.	O
+
+There	O
+are	O
+also	O
+implications	O
+for	O
+recommendations	O
+and	O
+regulations	O
+regarding	O
+the	O
+use	O
+of	O
+clozapine	B-Chemical
+.	O
+
+Severe	O
+rhabdomyolysis	B-Disease
+and	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+secondary	O
+to	O
+concomitant	O
+use	O
+of	O
+simvastatin	B-Chemical
+,	O
+amiodarone	B-Chemical
+,	O
+and	O
+atazanavir	B-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+report	O
+a	O
+case	O
+of	O
+a	O
+severe	O
+interaction	O
+between	O
+simvastatin	B-Chemical
+,	O
+amiodarone	B-Chemical
+,	O
+and	O
+atazanavir	B-Chemical
+resulting	O
+in	O
+rhabdomyolysis	B-Disease
+and	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+A	O
+72	O
+-	O
+year	O
+-	O
+old	O
+white	O
+man	O
+with	O
+underlying	O
+human	B-Disease
+immunodeficiency	I-Disease
+virus	I-Disease
+,	O
+atrial	B-Disease
+fibrillation	I-Disease
+,	O
+coronary	B-Disease
+artery	I-Disease
+disease	I-Disease
+,	O
+and	O
+hyperlipidemia	B-Disease
+presented	O
+with	O
+generalized	O
+pain	B-Disease
+,	O
+fatigue	B-Disease
+,	O
+and	O
+dark	O
+orange	O
+urine	O
+for	O
+3	O
+days	O
+.	O
+
+The	O
+patient	O
+was	O
+taking	O
+80	O
+mg	O
+simvastatin	B-Chemical
+at	O
+bedtime	O
+(	O
+initiated	O
+27	O
+days	O
+earlier	O
+)	O
+;	O
+amiodarone	B-Chemical
+at	O
+a	O
+dose	O
+of	O
+400	O
+mg	O
+daily	O
+for	O
+7	O
+days	O
+,	O
+then	O
+200	O
+mg	O
+daily	O
+(	O
+initiated	O
+19	O
+days	O
+earlier	O
+)	O
+;	O
+and	O
+400	O
+mg	O
+atazanavir	B-Chemical
+daily	O
+(	O
+initiated	O
+at	O
+least	O
+2	O
+years	O
+previously	O
+)	O
+.	O
+
+Laboratory	O
+evaluation	O
+revealed	O
+66	O
+,	O
+680	O
+U	O
+/	O
+L	O
+creatine	B-Chemical
+kinase	O
+,	O
+93	O
+mg	O
+/	O
+dL	O
+blood	B-Chemical
+urea	I-Chemical
+nitrogen	I-Chemical
+,	O
+4	O
+.	O
+6	O
+mg	O
+/	O
+dL	O
+creatinine	B-Chemical
+,	O
+1579	O
+U	O
+/	O
+L	O
+aspartate	B-Chemical
+aminotransferase	O
+,	O
+and	O
+738	O
+U	O
+/	O
+L	O
+alanine	B-Chemical
+aminotransferase	O
+.	O
+
+Simvastatin	B-Chemical
+,	O
+amiodarone	B-Chemical
+,	O
+and	O
+the	O
+patient	O
+'	O
+s	O
+human	B-Disease
+immunodeficiency	I-Disease
+virus	I-Disease
+medications	O
+were	O
+all	O
+temporarily	O
+discontinued	O
+and	O
+the	O
+patient	O
+was	O
+given	O
+forced	O
+alkaline	O
+diuresis	O
+and	O
+started	O
+on	O
+dialysis	O
+.	O
+
+Nine	O
+days	O
+later	O
+the	O
+patient	O
+'	O
+s	O
+creatine	B-Chemical
+kinase	O
+had	O
+dropped	O
+to	O
+1695	O
+U	O
+/	O
+L	O
+and	O
+creatinine	B-Chemical
+was	O
+3	O
+.	O
+3	O
+mg	O
+/	O
+dL	O
+.	O
+
+The	O
+patient	O
+was	O
+discharged	O
+and	O
+continued	O
+outpatient	O
+dialysis	O
+for	O
+1	O
+month	O
+until	O
+his	O
+renal	O
+function	O
+recovered	O
+.	O
+
+DISCUSSION	O
+:	O
+The	O
+risk	O
+of	O
+rhabdomyolysis	B-Disease
+is	O
+increased	O
+in	O
+the	O
+presence	O
+of	O
+concomitant	O
+drugs	O
+that	O
+inhibit	O
+simvastatin	B-Chemical
+metabolism	O
+.	O
+
+Simvastatin	B-Chemical
+is	O
+metabolized	O
+by	O
+CYP3A4	O
+.	O
+
+Amiodarone	B-Chemical
+and	O
+atazanavir	B-Chemical
+are	O
+recognized	O
+CYP3A4	O
+inhibitors	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Pharmacokinetic	O
+differences	O
+in	O
+statins	B-Chemical
+are	O
+an	O
+important	O
+consideration	O
+for	O
+assessing	O
+the	O
+risk	O
+of	O
+potential	O
+drug	O
+interactions	O
+.	O
+
+In	O
+patients	O
+requiring	O
+the	O
+concurrent	O
+use	O
+of	O
+statins	B-Chemical
+and	O
+CYP3A4	O
+inhibitors	O
+,	O
+pravastatin	B-Chemical
+,	O
+fluvastatin	B-Chemical
+,	O
+and	O
+rosuvastatin	B-Chemical
+carry	O
+the	O
+lowest	O
+risk	O
+of	O
+drug	O
+interactions	O
+;	O
+atorvastatin	B-Chemical
+carries	O
+moderate	O
+risk	O
+,	O
+whereas	O
+simvastatin	B-Chemical
+and	O
+lovastatin	B-Chemical
+have	O
+the	O
+highest	O
+risk	O
+and	O
+should	O
+be	O
+avoided	O
+in	O
+patients	O
+taking	O
+concomitant	O
+CYP3A4	O
+inhibitors	O
+.	O
+
+Interaction	O
+between	O
+warfarin	B-Chemical
+and	O
+levofloxacin	B-Chemical
+:	O
+case	O
+series	O
+.	O
+
+Warfarin	B-Chemical
+is	O
+the	O
+most	O
+widely	O
+used	O
+oral	O
+anticoagulant	O
+and	O
+is	O
+indicated	O
+for	O
+many	O
+clinical	O
+conditions	O
+.	O
+
+Levofloxacin	B-Chemical
+,	O
+a	O
+fluoroquinolone	B-Chemical
+,	O
+is	O
+one	O
+of	O
+the	O
+most	O
+commonly	O
+prescribed	O
+antibiotics	O
+in	O
+clinical	O
+practice	O
+and	O
+is	O
+effective	O
+against	O
+Gram	O
+-	O
+positive	O
+,	O
+Gram	O
+-	O
+negative	O
+,	O
+and	O
+atypical	O
+bacteria	O
+.	O
+
+While	O
+small	O
+prospective	O
+studies	O
+have	O
+not	O
+revealed	O
+any	O
+significant	O
+drug	O
+-	O
+drug	O
+interaction	O
+between	O
+warfarin	B-Chemical
+and	O
+levofloxacin	B-Chemical
+,	O
+several	O
+case	O
+reports	O
+have	O
+indicated	O
+that	O
+levofloxacin	B-Chemical
+may	O
+significantly	O
+potentiate	O
+the	O
+anticoagulation	O
+effect	O
+of	O
+warfarin	B-Chemical
+.	O
+
+We	O
+report	O
+3	O
+cases	O
+of	O
+serious	O
+bleeding	B-Disease
+complications	O
+that	O
+appear	O
+to	O
+be	O
+the	O
+result	O
+of	O
+the	O
+interaction	O
+between	O
+warfarin	B-Chemical
+and	O
+levofloxacin	B-Chemical
+.	O
+
+Physicians	O
+should	O
+be	O
+aware	O
+of	O
+this	O
+potential	O
+interaction	O
+and	O
+use	O
+caution	O
+when	O
+prescribing	O
+levofloxacin	B-Chemical
+to	O
+patients	O
+taking	O
+warfarin	B-Chemical
+.	O
+
+Mutations	O
+associated	O
+with	O
+lamivudine	B-Chemical
+-	O
+resistance	O
+in	O
+therapy	O
+-	O
+na	B-Chemical
+ve	O
+hepatitis	B-Disease
+B	I-Disease
+virus	I-Disease
+(	I-Disease
+HBV	I-Disease
+)	I-Disease
+infected	I-Disease
+patients	O
+with	O
+and	O
+without	O
+HIV	B-Disease
+co	I-Disease
+-	I-Disease
+infection	I-Disease
+:	O
+implications	O
+for	O
+antiretroviral	O
+therapy	O
+in	O
+HBV	B-Disease
+and	I-Disease
+HIV	I-Disease
+co	I-Disease
+-	I-Disease
+infected	I-Disease
+South	O
+African	O
+patients	O
+.	O
+
+This	O
+was	O
+an	O
+exploratory	O
+study	O
+to	O
+investigate	O
+lamivudine	B-Chemical
+-	O
+resistant	O
+hepatitis	B-Disease
+B	I-Disease
+virus	O
+(	O
+HBV	O
+)	O
+strains	O
+in	O
+selected	O
+lamivudine	B-Chemical
+-	O
+na	B-Chemical
+ve	O
+HBV	O
+carriers	O
+with	O
+and	O
+without	O
+human	B-Disease
+immunodeficiency	I-Disease
+virus	I-Disease
+(	I-Disease
+HIV	I-Disease
+)	I-Disease
+co	I-Disease
+-	I-Disease
+infection	I-Disease
+in	O
+South	O
+African	O
+patients	O
+.	O
+
+Thirty	O
+-	O
+five	O
+lamivudine	B-Chemical
+-	O
+na	B-Chemical
+ve	O
+HBV	B-Disease
+infected	I-Disease
+patients	O
+with	O
+or	O
+without	O
+HIV	B-Disease
+co	I-Disease
+-	I-Disease
+infection	I-Disease
+were	O
+studied	O
+:	O
+15	O
+chronic	O
+HBV	B-Disease
+mono	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+and	O
+20	O
+HBV	B-Disease
+-	I-Disease
+HIV	I-Disease
+co	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+.	O
+
+The	O
+latter	O
+group	O
+was	O
+further	O
+sub	O
+-	O
+divided	O
+into	O
+13	O
+occult	O
+HBV	O
+(	O
+HBsAg	B-Chemical
+-	O
+negative	O
+)	O
+and	O
+7	O
+overt	O
+HBV	O
+(	O
+HBsAg	B-Chemical
+-	O
+positive	O
+)	O
+patients	O
+.	O
+
+HBsAg	B-Chemical
+,	O
+anti	O
+-	O
+HBs	O
+,	O
+anti	O
+-	O
+HBc	O
+,	O
+and	O
+anti	O
+-	O
+HIV	O
+1	O
+/	O
+2	O
+were	O
+determined	O
+as	O
+part	O
+of	O
+routine	O
+diagnosis	O
+using	O
+Axsym	O
+assays	O
+(	O
+Abbott	O
+Laboratories	O
+,	O
+North	O
+Chicago	O
+,	O
+IL	O
+)	O
+.	O
+
+Serum	O
+samples	O
+were	O
+PCR	O
+amplified	O
+with	O
+HBV	O
+reverse	O
+transcriptase	O
+(	O
+RT	O
+)	O
+primers	O
+,	O
+followed	O
+by	O
+direct	O
+sequencing	O
+across	O
+the	O
+tyrosine	B-Chemical
+-	O
+methionine	B-Chemical
+-	O
+aspartate	B-Chemical
+-	O
+aspartate	B-Chemical
+(	O
+YMDD	O
+)	O
+motif	O
+of	O
+the	O
+major	O
+catalytic	O
+region	O
+in	O
+the	O
+C	O
+domain	O
+of	O
+the	O
+HBV	O
+RT	O
+enzyme	O
+.	O
+
+HBV	O
+viral	O
+load	O
+was	O
+performed	O
+with	O
+Amplicor	O
+HBV	O
+Monitor	O
+test	O
+v2	O
+.	O
+0	O
+(	O
+Roche	O
+Diagnostics	O
+,	O
+Penzberg	O
+,	O
+Germany	O
+)	O
+.	O
+
+HBV	O
+lamivudine	B-Chemical
+-	O
+resistant	O
+strains	O
+were	O
+detected	O
+in	O
+3	O
+of	O
+15	O
+mono	O
+-	O
+infected	O
+chronic	O
+hepatitis	B-Disease
+B	I-Disease
+patients	O
+and	O
+10	O
+of	O
+20	O
+HBV	B-Disease
+-	I-Disease
+HIV	I-Disease
+co	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+.	O
+
+To	O
+the	O
+best	O
+of	O
+our	O
+knowledge	O
+,	O
+this	O
+constitutes	O
+the	O
+first	O
+report	O
+of	O
+HBV	O
+lamivudine	B-Chemical
+-	O
+resistant	O
+strains	O
+in	O
+therapy	O
+-	O
+na	B-Chemical
+ve	O
+HBV	B-Disease
+-	I-Disease
+HIV	I-Disease
+co	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+.	O
+
+The	O
+HBV	O
+viral	O
+loads	O
+for	O
+mono	O
+-	O
+infected	O
+and	O
+co	O
+-	O
+infected	O
+patients	O
+ranged	O
+from	O
+3	O
+.	O
+32	O
+x	O
+10	O
+(	O
+2	O
+)	O
+to	O
+3	O
+.	O
+82	O
+x	O
+10	O
+(	O
+7	O
+)	O
+and	O
+<	O
+200	O
+to	O
+4	O
+.	O
+40	O
+x	O
+10	O
+(	O
+3	O
+)	O
+copies	O
+/	O
+ml	O
+,	O
+respectively	O
+.	O
+
+It	O
+remains	O
+to	O
+be	O
+seen	O
+whether	O
+such	O
+pre	O
+-	O
+existing	O
+antiviral	O
+mutations	O
+could	O
+result	O
+in	O
+widespread	O
+emergence	O
+of	O
+HBV	O
+resistant	O
+strains	O
+when	O
+lamivudine	B-Chemical
+-	O
+containing	O
+highly	O
+active	O
+antiretroviral	O
+(	O
+ARV	O
+)	O
+treatment	O
+(	O
+HAART	O
+)	O
+regimens	O
+become	O
+widely	O
+applied	O
+in	O
+South	O
+Africa	O
+,	O
+as	O
+this	O
+is	O
+likely	O
+to	O
+have	O
+potential	O
+implications	O
+in	O
+the	O
+management	O
+of	O
+HBV	B-Disease
+-	I-Disease
+HIV	I-Disease
+co	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+.	O
+
+Rabbit	B-Disease
+syndrome	I-Disease
+,	O
+antidepressant	B-Chemical
+use	O
+,	O
+and	O
+cerebral	O
+perfusion	O
+SPECT	O
+scan	O
+findings	O
+.	O
+
+The	O
+rabbit	B-Disease
+syndrome	I-Disease
+is	O
+an	O
+extrapyramidal	O
+side	O
+effect	O
+associated	O
+with	O
+chronic	O
+neuroleptic	O
+therapy	O
+.	O
+
+Its	O
+occurrence	O
+in	O
+a	O
+patient	O
+being	O
+treated	O
+with	O
+imipramine	B-Chemical
+is	O
+described	O
+,	O
+representing	O
+the	O
+first	O
+reported	O
+case	O
+of	O
+this	O
+syndrome	O
+in	O
+conjunction	O
+with	O
+antidepressants	B-Chemical
+.	O
+
+Repeated	O
+cerebral	O
+perfusion	O
+SPECT	O
+scans	O
+revealed	O
+decreased	B-Disease
+basal	I-Disease
+ganglia	I-Disease
+perfusion	I-Disease
+while	O
+the	O
+movement	B-Disease
+disorder	I-Disease
+was	O
+present	O
+,	O
+and	O
+a	O
+return	O
+to	O
+normal	O
+perfusion	O
+when	O
+the	O
+rabbit	B-Disease
+syndrome	I-Disease
+resolved	O
+.	O
+
+Estrogen	O
+prevents	O
+cholesteryl	B-Chemical
+ester	I-Chemical
+accumulation	O
+in	O
+macrophages	O
+induced	O
+by	O
+the	O
+HIV	O
+protease	O
+inhibitor	O
+ritonavir	B-Chemical
+.	O
+
+Individuals	O
+with	O
+HIV	O
+can	O
+now	O
+live	O
+long	O
+lives	O
+with	O
+drug	O
+therapy	O
+that	O
+often	O
+includes	O
+protease	O
+inhibitors	O
+such	O
+as	O
+ritonavir	B-Chemical
+.	O
+
+Many	O
+patients	O
+,	O
+however	O
+,	O
+develop	O
+negative	O
+long	O
+-	O
+term	O
+side	O
+effects	O
+such	O
+as	O
+premature	B-Disease
+atherosclerosis	I-Disease
+.	O
+
+We	O
+have	O
+previously	O
+demonstrated	O
+that	O
+ritonavir	B-Chemical
+treatment	O
+increases	O
+atherosclerotic	B-Disease
+lesion	I-Disease
+formation	O
+in	O
+male	O
+mice	O
+to	O
+a	O
+greater	O
+extent	O
+than	O
+in	O
+female	O
+mice	O
+.	O
+
+Furthermore	O
+,	O
+peripheral	O
+blood	O
+monocytes	O
+isolated	O
+from	O
+ritonavir	B-Chemical
+-	O
+treated	O
+females	O
+had	O
+less	O
+cholesteryl	B-Chemical
+ester	I-Chemical
+accumulation	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+have	O
+investigated	O
+the	O
+molecular	O
+mechanisms	O
+by	O
+which	O
+female	O
+hormones	O
+influence	O
+cholesterol	B-Chemical
+metabolism	O
+in	O
+macrophages	O
+in	O
+response	O
+to	O
+the	O
+HIV	O
+protease	O
+inhibitor	O
+ritonavir	B-Chemical
+.	O
+
+We	O
+have	O
+utilized	O
+the	O
+human	O
+monocyte	O
+cell	O
+line	O
+,	O
+THP	O
+-	O
+1	O
+as	O
+a	O
+model	O
+to	O
+address	O
+this	O
+question	O
+.	O
+
+Briefly	O
+,	O
+cells	O
+were	O
+differentiated	O
+for	O
+72	O
+h	O
+with	O
+100	O
+nM	O
+PMA	O
+to	O
+obtain	O
+a	O
+macrophage	O
+-	O
+like	O
+phenotype	O
+in	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+1	O
+nM	O
+17beta	B-Chemical
+-	I-Chemical
+estradiol	I-Chemical
+(	O
+E2	B-Chemical
+)	O
+,	O
+100	O
+nM	O
+progesterone	B-Chemical
+or	O
+vehicle	O
+(	O
+0	O
+.	O
+01	O
+%	O
+ethanol	B-Chemical
+)	O
+.	O
+
+Cells	O
+were	O
+then	O
+treated	O
+with	O
+30	O
+ng	O
+/	O
+ml	O
+ritonavir	B-Chemical
+or	O
+vehicle	O
+in	O
+the	O
+presence	O
+of	O
+aggregated	O
+LDL	O
+for	O
+24	O
+h	O
+.	O
+
+Cell	O
+extracts	O
+were	O
+harvested	O
+,	O
+and	O
+lipid	O
+or	O
+total	O
+RNA	O
+was	O
+isolated	O
+.	O
+
+E2	B-Chemical
+decreased	O
+the	O
+accumulation	O
+of	O
+cholesteryl	B-Chemical
+esters	I-Chemical
+in	O
+macrophages	O
+following	O
+ritonavir	B-Chemical
+treatment	O
+.	O
+
+Ritonavir	B-Chemical
+increased	O
+the	O
+expression	O
+of	O
+the	O
+scavenger	O
+receptor	O
+,	O
+CD36	O
+mRNA	O
+,	O
+responsible	O
+for	O
+the	O
+uptake	O
+of	O
+LDL	O
+.	O
+
+Additionally	O
+,	O
+ritonavir	B-Chemical
+treatment	O
+selectively	O
+increased	O
+the	O
+relative	O
+levels	O
+of	O
+PPARgamma	O
+mRNA	O
+,	O
+a	O
+transcription	O
+factor	O
+responsible	O
+for	O
+the	O
+regulation	O
+of	O
+CD36	O
+mRNA	O
+expression	O
+.	O
+
+Treatment	O
+with	O
+E2	B-Chemical
+,	O
+however	O
+,	O
+failed	O
+to	O
+prevent	O
+these	O
+increases	O
+at	O
+the	O
+mRNA	O
+level	O
+.	O
+
+E2	B-Chemical
+did	O
+,	O
+however	O
+,	O
+significantly	O
+suppress	O
+CD36	O
+protein	O
+levels	O
+as	O
+measured	O
+by	O
+fluorescent	O
+immunocytochemistry	O
+.	O
+
+This	O
+data	O
+suggests	O
+that	O
+E2	B-Chemical
+modifies	O
+the	O
+expression	O
+of	O
+CD36	O
+at	O
+the	O
+level	O
+of	O
+protein	O
+expression	O
+in	O
+monocyte	O
+-	O
+derived	O
+macrophages	O
+resulting	O
+in	O
+reduced	O
+cholesteryl	B-Chemical
+ester	I-Chemical
+accumulation	O
+following	O
+ritonavir	B-Chemical
+treatment	O
+.	O
+
+Acute	O
+hepatitis	B-Disease
+attack	O
+after	O
+exposure	O
+to	O
+telithromycin	B-Chemical
+.	O
+
+INTRODUCTION	O
+:	O
+Antibiotic	O
+-	O
+associated	O
+hepatotoxicity	B-Disease
+is	O
+rare	O
+.	O
+
+With	O
+widespread	O
+use	O
+of	O
+antimicrobial	O
+agents	O
+,	O
+however	O
+,	O
+hepatic	B-Disease
+injury	I-Disease
+occurs	O
+frequently	O
+,	O
+and	O
+among	O
+adverse	B-Disease
+drug	I-Disease
+reactions	I-Disease
+,	O
+idiosyncratic	O
+reactions	O
+are	O
+the	O
+most	O
+serious	O
+.	O
+
+CASE	O
+SUMMARY	O
+:	O
+A	O
+25	O
+-	O
+year	O
+-	O
+old	O
+male	O
+patient	O
+,	O
+with	O
+a	O
+height	O
+of	O
+175	O
+cm	O
+and	O
+weight	O
+of	O
+72	O
+kg	O
+presented	O
+to	O
+Marmara	O
+University	O
+Hospital	O
+Emergency	O
+Department	O
+,	O
+Istanbul	O
+,	O
+Turkey	O
+,	O
+with	O
+5	O
+days	O
+'	O
+history	O
+of	O
+jaundice	B-Disease
+,	O
+malaise	O
+,	O
+nausea	B-Disease
+,	O
+and	O
+vomiting	B-Disease
+.	O
+
+He	O
+had	O
+been	O
+prescribed	O
+telithromycin	B-Chemical
+400	O
+mg	O
+/	O
+d	O
+PO	O
+to	O
+treat	O
+an	O
+upper	B-Disease
+respiratory	I-Disease
+tract	I-Disease
+infection	I-Disease
+7	O
+days	O
+prior	O
+.	O
+
+Admission	O
+laboratory	O
+tests	O
+were	O
+as	O
+follows	O
+:	O
+alanine	B-Chemical
+aminotransferase	O
+,	O
+67	O
+U	O
+/	O
+L	O
+(	O
+reference	O
+range	O
+,	O
+10	O
+-	O
+37	O
+U	O
+/	O
+L	O
+)	O
+;	O
+aspartate	B-Chemical
+aminotransferase	O
+,	O
+98	O
+U	O
+/	O
+L	O
+(	O
+10	O
+-	O
+40	O
+U	O
+/	O
+L	O
+)	O
+;	O
+alkaline	O
+phosphatase	O
+,	O
+513	O
+U	O
+/	O
+L	O
+(	O
+0	O
+-	O
+270	O
+U	O
+/	O
+L	O
+)	O
+;	O
+gamma	O
+-	O
+glutamyltransferase	O
+,	O
+32	O
+U	O
+/	O
+L	O
+(	O
+7	O
+-	O
+49	O
+U	O
+/	O
+L	O
+)	O
+;	O
+amylase	O
+,	O
+46	O
+U	O
+/	O
+L	O
+(	O
+0	O
+-	O
+220	O
+U	O
+/	O
+L	O
+)	O
+;	O
+total	O
+bilirubin	B-Chemical
+,	O
+20	O
+.	O
+1	O
+mg	O
+/	O
+dL	O
+(	O
+0	O
+.	O
+2	O
+-	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+dL	O
+)	O
+;	O
+direct	O
+bilirubin	B-Chemical
+,	O
+14	O
+.	O
+8	O
+mg	O
+/	O
+dL	O
+(	O
+0	O
+-	O
+0	O
+.	O
+3	O
+mg	O
+/	O
+dL	O
+)	O
+;	O
+and	O
+albumin	O
+,	O
+4	O
+.	O
+7	O
+mg	O
+/	O
+dL	O
+(	O
+3	O
+.	O
+5	O
+-	O
+5	O
+.	O
+4	O
+mg	O
+/	O
+dL	O
+)	O
+.	O
+
+No	O
+toxin	O
+,	O
+alcohol	B-Chemical
+,	O
+or	O
+other	O
+drugs	O
+were	O
+reported	O
+.	O
+
+The	O
+patient	O
+had	O
+suffered	O
+a	O
+previous	O
+episode	O
+of	O
+"	O
+acute	O
+hepatitis	B-Disease
+of	O
+unknown	O
+origin	O
+,	O
+"	O
+that	O
+occurred	O
+after	O
+telithromycin	B-Chemical
+usage	O
+.	O
+
+Both	O
+incidents	O
+occurred	O
+within	O
+a	O
+year	O
+.	O
+
+DISCUSSION	O
+:	O
+Telithromycin	B-Chemical
+is	O
+the	O
+first	O
+of	O
+the	O
+ketolide	O
+antibacterials	O
+to	O
+receive	O
+US	O
+Food	O
+and	O
+Drug	O
+Administration	O
+approval	O
+for	O
+clinical	O
+use	O
+.	O
+
+It	O
+has	O
+been	O
+associated	O
+with	O
+infrequent	O
+and	O
+usually	O
+reversible	O
+severe	O
+hepatic	B-Disease
+dysfunction	I-Disease
+.	O
+
+Based	O
+on	O
+a	O
+score	O
+of	O
+8	O
+on	O
+the	O
+Naranjo	O
+adverse	B-Disease
+drug	I-Disease
+reaction	I-Disease
+probability	O
+scale	O
+,	O
+telithromycin	B-Chemical
+was	O
+the	O
+probable	O
+cause	O
+of	O
+acute	O
+hepatitis	B-Disease
+in	O
+this	O
+patient	O
+,	O
+and	O
+pathological	O
+findings	O
+suggested	O
+drug	O
+-	O
+induced	O
+toxic	B-Disease
+hepatitis	I-Disease
+.	O
+
+Recurrence	O
+of	O
+hepatitis	B-Disease
+attack	O
+might	O
+have	O
+been	O
+avoided	O
+if	O
+the	O
+initial	O
+incident	O
+had	O
+been	O
+communicated	O
+to	O
+the	O
+attending	O
+physician	O
+who	O
+prescribed	O
+telithromycin	B-Chemical
+the	O
+second	O
+time	O
+.	O
+
+CONCLUSION	O
+:	O
+Here	O
+we	O
+report	O
+a	O
+case	O
+of	O
+acute	O
+hepatitis	B-Disease
+probably	O
+associated	O
+with	O
+the	O
+administration	O
+of	O
+telithromycin	B-Chemical
+.	O
+
+A	O
+study	O
+on	O
+the	O
+effect	O
+of	O
+the	O
+duration	O
+of	O
+subcutaneous	O
+heparin	B-Chemical
+injection	O
+on	O
+bruising	B-Disease
+and	O
+pain	B-Disease
+.	O
+
+AIM	O
+:	O
+This	O
+study	O
+was	O
+carried	O
+out	O
+to	O
+determine	O
+the	O
+effect	O
+of	O
+injection	O
+duration	O
+on	O
+bruising	B-Disease
+and	O
+pain	B-Disease
+following	O
+the	O
+administration	O
+of	O
+the	O
+subcutaneous	O
+injection	O
+of	O
+heparin	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+Although	O
+different	O
+methods	O
+to	O
+prevent	O
+bruising	B-Disease
+and	O
+pain	B-Disease
+following	O
+the	O
+subcutaneous	O
+injection	O
+of	O
+heparin	B-Chemical
+have	O
+been	O
+widely	O
+studied	O
+and	O
+described	O
+,	O
+the	O
+effect	O
+of	O
+injection	O
+duration	O
+on	O
+the	O
+occurrence	O
+of	O
+bruising	B-Disease
+and	O
+pain	B-Disease
+is	O
+little	O
+documented	O
+.	O
+
+DESIGN	O
+:	O
+This	O
+study	O
+was	O
+designed	O
+as	O
+within	O
+-	O
+subject	O
+,	O
+quasi	O
+-	O
+experimental	O
+research	O
+.	O
+
+METHOD	O
+:	O
+The	O
+sample	O
+for	O
+the	O
+study	O
+consisted	O
+of	O
+50	O
+patients	O
+to	O
+whom	O
+subcutaneous	O
+heparin	B-Chemical
+was	O
+administered	O
+.	O
+
+Heparin	B-Chemical
+was	O
+injected	O
+over	O
+10	O
+seconds	O
+on	O
+the	O
+right	O
+abdominal	O
+site	O
+and	O
+30	O
+seconds	O
+on	O
+the	O
+left	O
+abdominal	O
+site	O
+.	O
+
+Injections	O
+areas	O
+were	O
+assessed	O
+for	O
+the	O
+presence	O
+of	O
+bruising	B-Disease
+at	O
+48	O
+and	O
+72	O
+hours	O
+after	O
+each	O
+injection	O
+.	O
+
+Dimensions	O
+of	O
+the	O
+bruising	B-Disease
+on	O
+the	O
+heparin	B-Chemical
+applied	O
+areas	O
+were	O
+measured	O
+using	O
+transparent	O
+millimetric	O
+measuring	O
+paper	O
+.	O
+
+The	O
+visual	O
+analog	O
+scale	O
+(	O
+VAS	O
+)	O
+was	O
+used	O
+to	O
+measure	O
+pain	B-Disease
+intensity	O
+and	O
+a	O
+stop	O
+-	O
+watch	O
+was	O
+used	O
+to	O
+time	O
+the	O
+pain	B-Disease
+period	O
+.	O
+
+Data	O
+were	O
+analysed	O
+using	O
+chi	O
+-	O
+square	O
+test	O
+,	O
+Mann	O
+-	O
+Whitney	O
+U	O
+,	O
+Wilcoxon	O
+signed	O
+ranks	O
+tests	O
+and	O
+correlation	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+percentage	O
+of	O
+bruising	B-Disease
+occurrence	O
+was	O
+64	O
+%	O
+with	O
+the	O
+injection	O
+of	O
+10	O
+seconds	O
+duration	O
+and	O
+42	O
+%	O
+in	O
+the	O
+30	O
+-	O
+second	O
+injection	O
+.	O
+
+It	O
+was	O
+determined	O
+that	O
+the	O
+size	O
+of	O
+the	O
+bruising	B-Disease
+was	O
+smaller	O
+in	O
+the	O
+30	O
+-	O
+second	O
+injection	O
+.	O
+
+Pain	B-Disease
+intensity	O
+and	O
+pain	B-Disease
+period	O
+were	O
+statistically	O
+significantly	O
+lower	O
+for	O
+the	O
+30	O
+-	O
+second	O
+injection	O
+than	O
+for	O
+the	O
+10	O
+-	O
+second	O
+injection	O
+.	O
+
+CONCLUSIONS	O
+:	O
+It	O
+was	O
+determined	O
+that	O
+injection	O
+duration	O
+had	O
+an	O
+effect	O
+on	O
+bruising	B-Disease
+and	O
+pain	B-Disease
+following	O
+the	O
+subcutaneous	O
+administration	O
+of	O
+heparin	B-Chemical
+.	O
+
+This	O
+study	O
+should	O
+be	O
+repeated	O
+on	O
+a	O
+larger	O
+sample	O
+.	O
+
+RELEVANCE	O
+TO	O
+CLINICAL	O
+PRACTICE	O
+:	O
+When	O
+administering	O
+subcutaneous	O
+heparin	B-Chemical
+injections	O
+,	O
+it	O
+is	O
+important	O
+to	O
+extend	O
+the	O
+duration	O
+of	O
+the	O
+injection	O
+.	O
+
+Acute	B-Disease
+liver	I-Disease
+failure	I-Disease
+in	O
+two	O
+patients	O
+with	O
+regular	O
+alcohol	B-Chemical
+consumption	O
+ingesting	O
+paracetamol	B-Chemical
+at	O
+therapeutic	O
+dosage	O
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+possible	O
+role	O
+of	O
+alcohol	B-Chemical
+in	O
+the	O
+development	O
+of	O
+hepatotoxicity	B-Disease
+associated	O
+with	O
+therapeutic	O
+doses	O
+of	O
+paracetamol	B-Chemical
+(	O
+acetaminophen	B-Chemical
+)	O
+is	O
+currently	O
+debated	O
+.	O
+
+CASE	O
+REPORT	O
+:	O
+We	O
+describe	O
+2	O
+patients	O
+who	O
+were	O
+regular	O
+consumers	O
+of	O
+alcohol	B-Chemical
+and	O
+who	O
+developed	O
+liver	B-Disease
+failure	I-Disease
+within	O
+3	O
+-	O
+5	O
+days	O
+after	O
+hospitalization	O
+and	O
+stopping	O
+alcohol	B-Chemical
+consumption	O
+while	O
+being	O
+treated	O
+with	O
+4	O
+g	O
+paracetamol	B-Chemical
+/	O
+day	O
+.	O
+
+A	O
+paracetamol	B-Chemical
+serum	O
+level	O
+obtained	O
+in	O
+one	O
+of	O
+these	O
+patients	O
+was	O
+not	O
+in	O
+the	O
+toxic	O
+range	O
+.	O
+
+Possible	O
+risk	O
+factors	O
+for	O
+the	O
+development	O
+of	O
+hepatotoxicity	B-Disease
+in	O
+patients	O
+treated	O
+with	O
+therapeutic	O
+doses	O
+of	O
+paracetamol	B-Chemical
+are	O
+discussed	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+patients	O
+with	O
+risk	O
+factors	O
+,	O
+e	O
+.	O
+g	O
+.	O
+regular	O
+consumption	O
+of	O
+alcohol	B-Chemical
+,	O
+liver	B-Disease
+failure	I-Disease
+is	O
+possible	O
+when	O
+therapeutic	O
+doses	O
+are	O
+ingested	O
+.	O
+
+We	O
+propose	O
+that	O
+the	O
+paracetamol	B-Chemical
+dose	O
+should	O
+not	O
+exceed	O
+2	O
+g	O
+/	O
+day	O
+in	O
+such	O
+patients	O
+and	O
+that	O
+their	O
+liver	O
+function	O
+should	O
+be	O
+monitored	O
+closely	O
+while	O
+being	O
+treated	O
+with	O
+paracetamol	B-Chemical
+.	O
+
+Associations	O
+between	O
+use	O
+of	O
+benzodiazepines	B-Chemical
+or	O
+related	O
+drugs	O
+and	O
+health	O
+,	O
+physical	O
+abilities	O
+and	O
+cognitive	O
+function	O
+:	O
+a	O
+non	O
+-	O
+randomised	O
+clinical	O
+study	O
+in	O
+the	O
+elderly	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+describe	O
+associations	O
+between	O
+the	O
+use	O
+of	O
+benzodiazepines	B-Chemical
+or	O
+related	O
+drugs	O
+(	O
+BZDs	B-Chemical
+/	O
+RDs	O
+)	O
+and	O
+health	O
+,	O
+functional	O
+abilities	O
+and	O
+cognitive	O
+function	O
+in	O
+the	O
+elderly	O
+.	O
+
+METHODS	O
+:	O
+A	O
+non	O
+-	O
+randomised	O
+clinical	O
+study	O
+of	O
+patients	O
+aged	O
+>	O
+or	O
+=	O
+65	O
+years	O
+admitted	O
+to	O
+acute	O
+hospital	O
+wards	O
+during	O
+1	O
+month	O
+.	O
+
+164	O
+patients	O
+(	O
+mean	O
+age	O
++	O
+/	O
+-	O
+standard	O
+deviation	O
+[	O
+SD	O
+]	O
+81	O
+.	O
+6	O
++	O
+/	O
+-	O
+6	O
+.	O
+8	O
+years	O
+)	O
+were	O
+admitted	O
+.	O
+
+Of	O
+these	O
+,	O
+nearly	O
+half	O
+(	O
+n	O
+=	O
+78	O
+)	O
+had	O
+used	O
+BZDs	B-Chemical
+/	O
+RDs	O
+before	O
+admission	O
+,	O
+and	O
+the	O
+remainder	O
+(	O
+n	O
+=	O
+86	O
+)	O
+were	O
+non	O
+-	O
+users	O
+.	O
+
+Cognitive	O
+ability	O
+was	O
+assessed	O
+by	O
+the	O
+Mini	O
+-	O
+Mental	O
+State	O
+Examination	O
+(	O
+MMSE	O
+)	O
+.	O
+
+Patients	O
+scoring	O
+>	O
+or	O
+=	O
+20	O
+MMSE	O
+sum	O
+points	O
+were	O
+interviewed	O
+(	O
+n	O
+=	O
+79	O
+)	O
+and	O
+questioned	O
+regarding	O
+symptoms	O
+and	O
+functional	O
+abilities	O
+during	O
+the	O
+week	O
+prior	O
+to	O
+admission	O
+.	O
+
+Data	O
+on	O
+use	O
+of	O
+BZDs	B-Chemical
+/	O
+RDs	O
+before	O
+admission	O
+,	O
+current	O
+medications	O
+and	O
+discharge	O
+diagnoses	O
+were	O
+collected	O
+from	O
+medical	O
+records	O
+.	O
+
+Health	O
+,	O
+physical	O
+abilities	O
+and	O
+cognitive	O
+function	O
+were	O
+compared	O
+between	O
+BZD	O
+/	O
+RD	O
+users	O
+and	O
+non	O
+-	O
+users	O
+,	O
+and	O
+adjustments	O
+were	O
+made	O
+for	O
+confounding	O
+variables	O
+.	O
+
+The	O
+residual	O
+serum	O
+concentrations	O
+of	O
+oxazepam	B-Chemical
+,	O
+temazepam	B-Chemical
+and	O
+zopiclone	B-Chemical
+were	O
+analysed	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+duration	O
+of	O
+BZD	O
+/	O
+RD	O
+use	O
+was	O
+7	O
++	O
+/	O
+-	O
+7	O
+years	O
+(	O
+range	O
+1	O
+-	O
+31	O
+)	O
+.	O
+
+Two	O
+or	O
+three	O
+BZDs	B-Chemical
+/	O
+RDs	O
+were	O
+concomitantly	O
+taken	O
+by	O
+26	O
+%	O
+of	O
+users	O
+(	O
+n	O
+=	O
+20	O
+)	O
+.	O
+
+Long	O
+-	O
+term	O
+use	O
+of	O
+these	O
+drugs	O
+was	O
+associated	O
+with	O
+female	O
+sex	O
+and	O
+use	O
+of	O
+a	O
+higher	O
+number	O
+of	O
+drugs	O
+with	O
+effects	O
+on	O
+the	O
+CNS	O
+,	O
+which	O
+tended	O
+to	O
+be	O
+related	O
+to	O
+diagnosed	O
+dementia	B-Disease
+.	O
+
+After	O
+adjustment	O
+for	O
+these	O
+variables	O
+as	O
+confounders	O
+,	O
+use	O
+of	O
+BZDs	B-Chemical
+/	O
+RDs	O
+was	O
+not	O
+associated	O
+with	O
+cognitive	O
+function	O
+as	O
+measured	O
+by	O
+the	O
+MMSE	O
+.	O
+
+However	O
+,	O
+use	O
+of	O
+BZDs	B-Chemical
+/	O
+RDs	O
+was	O
+associated	O
+with	O
+dizziness	B-Disease
+,	O
+inability	B-Disease
+to	I-Disease
+sleep	I-Disease
+after	O
+awaking	O
+at	O
+night	O
+and	O
+tiredness	B-Disease
+in	O
+the	O
+mornings	O
+during	O
+the	O
+week	O
+prior	O
+to	O
+admission	O
+and	O
+with	O
+stronger	O
+depressive	B-Disease
+symptoms	I-Disease
+measured	O
+at	O
+the	O
+beginning	O
+of	O
+the	O
+hospital	O
+stay	O
+.	O
+
+Use	O
+of	O
+BZDs	B-Chemical
+/	O
+RDs	O
+tended	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+reduced	O
+ability	O
+to	O
+walk	O
+and	O
+shorter	O
+night	O
+-	O
+time	O
+sleep	O
+during	O
+the	O
+week	O
+prior	O
+to	O
+admission	O
+.	O
+
+A	O
+higher	O
+residual	O
+serum	O
+concentration	O
+of	O
+temazepam	B-Chemical
+correlated	O
+with	O
+a	O
+lower	O
+MMSE	O
+sum	O
+score	O
+after	O
+adjustment	O
+for	O
+confounding	O
+variables	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Long	O
+-	O
+term	O
+use	O
+and	O
+concomitant	O
+use	O
+of	O
+more	O
+than	O
+one	O
+BZD	O
+/	O
+RD	O
+were	O
+common	O
+in	O
+elderly	O
+patients	O
+hospitalised	O
+because	O
+of	O
+acute	O
+illnesses	O
+.	O
+
+Long	O
+-	O
+term	O
+use	O
+was	O
+associated	O
+with	O
+daytime	O
+and	O
+night	O
+-	O
+time	O
+symptoms	O
+indicative	O
+of	O
+poorer	O
+health	O
+and	O
+potentially	O
+caused	O
+by	O
+the	O
+adverse	O
+effects	O
+of	O
+these	O
+drugs	O
+.	O
+
+Acute	O
+vocal	B-Disease
+fold	I-Disease
+palsy	I-Disease
+after	O
+acute	O
+disulfiram	B-Chemical
+intoxication	O
+.	O
+
+Acute	O
+peripheral	B-Disease
+neuropathy	I-Disease
+caused	O
+by	O
+a	O
+disulfiram	B-Chemical
+overdose	B-Disease
+is	O
+very	O
+rare	O
+and	O
+there	O
+is	O
+no	O
+report	O
+of	O
+it	O
+leading	O
+to	O
+vocal	B-Disease
+fold	I-Disease
+palsy	I-Disease
+.	O
+
+A	O
+49	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+was	O
+transferred	O
+to	O
+our	O
+department	O
+because	O
+of	O
+quadriparesis	B-Disease
+,	O
+lancinating	O
+pain	B-Disease
+,	O
+sensory	B-Disease
+loss	I-Disease
+,	O
+and	O
+paresthesia	B-Disease
+of	O
+the	O
+distal	O
+limbs	O
+.	O
+
+One	O
+month	O
+previously	O
+,	O
+she	O
+had	O
+taken	O
+a	O
+single	O
+high	O
+dose	O
+of	O
+disulfiram	B-Chemical
+(	O
+130	O
+tablets	O
+of	O
+ALCOHOL	B-Chemical
+STOP	O
+TAB	O
+,	O
+Shin	O
+-	O
+Poong	O
+Pharm	O
+.	O
+Co	O
+.	O
+,	O
+Ansan	O
+,	O
+Korea	O
+)	O
+in	O
+a	O
+suicide	O
+attempt	O
+.	O
+
+She	O
+was	O
+not	O
+an	O
+alcoholic	O
+.	O
+
+For	O
+the	O
+first	O
+few	O
+days	O
+after	O
+ingestion	O
+,	O
+she	O
+was	O
+in	O
+a	O
+confused	O
+state	O
+and	O
+had	O
+mild	O
+to	O
+moderate	O
+ataxia	B-Disease
+and	O
+giddiness	B-Disease
+.	O
+
+She	O
+noticed	O
+hoarseness	B-Disease
+and	O
+distally	O
+accentuated	O
+motor	O
+and	O
+sensory	O
+dysfunction	O
+after	O
+she	O
+had	O
+recovered	O
+from	O
+this	O
+state	O
+.	O
+
+A	O
+nerve	O
+conduction	O
+study	O
+was	O
+consistent	O
+with	O
+severe	O
+sensorimotor	O
+axonal	O
+polyneuropathy	B-Disease
+.	O
+
+Laryngeal	O
+electromyography	O
+(	O
+thyroarytenoid	O
+muscle	O
+)	O
+showed	O
+ample	O
+denervation	O
+potentials	O
+.	O
+
+Laryngoscopy	O
+revealed	O
+asymmetric	O
+vocal	O
+fold	O
+movements	O
+during	O
+phonation	O
+.	O
+
+Her	O
+vocal	O
+change	O
+and	O
+weakness	O
+began	O
+to	O
+improve	O
+spontaneously	O
+about	O
+3	O
+weeks	O
+after	O
+transfer	O
+.	O
+
+This	O
+was	O
+a	O
+case	O
+of	O
+acute	O
+palsy	B-Disease
+of	O
+the	O
+recurrent	O
+laryngeal	O
+nerve	O
+and	O
+superimposed	O
+severe	O
+acute	O
+sensorimotor	O
+axonal	O
+polyneuropathy	B-Disease
+caused	O
+by	O
+high	O
+-	O
+dose	O
+disulfiram	B-Chemical
+intoxication	O
+.	O
+
+Encephalopathy	B-Disease
+induced	O
+by	O
+levetiracetam	B-Chemical
+added	O
+to	O
+valproate	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+We	O
+report	O
+on	O
+the	O
+manifestation	O
+of	O
+a	O
+levetiracetam	B-Chemical
+(	O
+LEV	B-Chemical
+)	O
+-	O
+induced	O
+encephalopathy	B-Disease
+.	O
+
+FINDINGS	O
+:	O
+A	O
+28	O
+-	O
+year	O
+-	O
+old	O
+man	O
+suffering	O
+from	O
+idiopathic	B-Disease
+epilepsy	I-Disease
+with	O
+generalized	O
+seizures	B-Disease
+was	O
+treated	O
+with	O
+LEV	B-Chemical
+(	O
+3000	O
+mg	O
+)	O
+added	O
+to	O
+valproate	B-Chemical
+(	O
+VPA	B-Chemical
+)	O
+(	O
+2000	O
+mg	O
+)	O
+.	O
+
+Frequency	O
+of	O
+generalized	O
+tonic	B-Disease
+-	I-Disease
+clonic	I-Disease
+seizures	I-Disease
+increased	O
+from	O
+one	O
+per	O
+6	O
+months	O
+to	O
+two	O
+per	O
+month	O
+.	O
+
+Neuropsychological	O
+testing	O
+showed	O
+impaired	B-Disease
+word	I-Disease
+fluency	I-Disease
+,	I-Disease
+psychomotor	I-Disease
+speed	I-Disease
+and	I-Disease
+working	I-Disease
+memory	I-Disease
+.	O
+
+The	O
+interictal	O
+electroencephalogram	O
+(	O
+EEG	O
+)	O
+showed	O
+a	O
+generalized	O
+slowing	O
+to	O
+5	O
+per	O
+second	O
+theta	O
+rhythms	O
+with	O
+bilateral	O
+generalized	O
+high	O
+-	O
+amplitude	O
+discharges	O
+.	O
+
+OUTCOME	O
+:	O
+Following	O
+discontinuation	O
+of	O
+LEV	B-Chemical
+,	O
+EEG	O
+and	O
+neuropsychological	O
+findings	O
+improved	O
+and	O
+seizure	B-Disease
+frequency	O
+decreased	O
+.	O
+
+Norepinephrine	B-Chemical
+signaling	O
+through	O
+beta	O
+-	O
+adrenergic	O
+receptors	O
+is	O
+critical	O
+for	O
+expression	O
+of	O
+cocaine	B-Chemical
+-	O
+induced	O
+anxiety	B-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Cocaine	B-Chemical
+is	O
+a	O
+widely	O
+abused	O
+psychostimulant	O
+that	O
+has	O
+both	O
+rewarding	O
+and	O
+aversive	O
+properties	O
+.	O
+
+While	O
+the	O
+mechanisms	O
+underlying	O
+cocaine	B-Chemical
+'	O
+s	O
+rewarding	O
+effects	O
+have	O
+been	O
+studied	O
+extensively	O
+,	O
+less	O
+attention	O
+has	O
+been	O
+paid	O
+to	O
+the	O
+unpleasant	O
+behavioral	O
+states	O
+induced	O
+by	O
+cocaine	B-Chemical
+,	O
+such	O
+as	O
+anxiety	B-Disease
+.	O
+
+METHODS	O
+:	O
+In	O
+this	O
+study	O
+,	O
+we	O
+evaluated	O
+the	O
+performance	O
+of	O
+dopamine	B-Chemical
+beta	O
+-	O
+hydroxylase	O
+knockout	O
+(	O
+Dbh	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+,	O
+which	O
+lack	O
+norepinephrine	B-Chemical
+(	O
+NE	B-Chemical
+)	O
+,	O
+in	O
+the	O
+elevated	O
+plus	O
+maze	O
+(	O
+EPM	O
+)	O
+to	O
+examine	O
+the	O
+contribution	O
+of	O
+noradrenergic	O
+signaling	O
+to	O
+cocaine	B-Chemical
+-	O
+induced	O
+anxiety	B-Disease
+.	O
+
+RESULTS	O
+:	O
+We	O
+found	O
+that	O
+cocaine	B-Chemical
+dose	O
+-	O
+dependently	O
+increased	O
+anxiety	B-Disease
+-	O
+like	O
+behavior	O
+in	O
+control	O
+(	O
+Dbh	O
++	O
+/	O
+-	O
+)	O
+mice	O
+,	O
+as	O
+measured	O
+by	O
+a	O
+decrease	O
+in	O
+open	O
+arm	O
+exploration	O
+.	O
+
+The	O
+Dbh	O
+-	O
+/	O
+-	O
+mice	O
+had	O
+normal	O
+baseline	O
+performance	O
+in	O
+the	O
+EPM	O
+but	O
+were	O
+completely	O
+resistant	O
+to	O
+the	O
+anxiogenic	O
+effects	O
+of	O
+cocaine	B-Chemical
+.	O
+
+Cocaine	B-Chemical
+-	O
+induced	O
+anxiety	B-Disease
+was	O
+also	O
+attenuated	O
+in	O
+Dbh	O
++	O
+/	O
+-	O
+mice	O
+following	O
+administration	O
+of	O
+disulfiram	B-Chemical
+,	O
+a	O
+dopamine	B-Chemical
+beta	O
+-	O
+hydroxylase	O
+(	O
+DBH	O
+)	O
+inhibitor	O
+.	O
+
+In	O
+experiments	O
+using	O
+specific	O
+adrenergic	O
+antagonists	O
+,	O
+we	O
+found	O
+that	O
+pretreatment	O
+with	O
+the	O
+beta	O
+-	O
+adrenergic	O
+receptor	O
+antagonist	O
+propranolol	B-Chemical
+blocked	O
+cocaine	B-Chemical
+-	O
+induced	O
+anxiety	B-Disease
+-	O
+like	O
+behavior	O
+in	O
+Dbh	O
++	O
+/	O
+-	O
+and	O
+wild	O
+-	O
+type	O
+C57BL6	O
+/	O
+J	O
+mice	O
+,	O
+while	O
+the	O
+alpha	O
+(	O
+1	O
+)	O
+antagonist	O
+prazosin	B-Chemical
+and	O
+the	O
+alpha	O
+(	O
+2	O
+)	O
+antagonist	O
+yohimbine	B-Chemical
+had	O
+no	O
+effect	O
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+results	O
+indicate	O
+that	O
+noradrenergic	O
+signaling	O
+via	O
+beta	O
+-	O
+adrenergic	O
+receptors	O
+is	O
+required	O
+for	O
+cocaine	B-Chemical
+-	O
+induced	O
+anxiety	B-Disease
+in	O
+mice	O
+.	O
+
+Hypothalamic	O
+prolactin	O
+receptor	O
+messenger	O
+ribonucleic	B-Chemical
+acid	I-Chemical
+levels	O
+,	O
+prolactin	O
+signaling	O
+,	O
+and	O
+hyperprolactinemic	B-Disease
+inhibition	O
+of	O
+pulsatile	O
+luteinizing	O
+hormone	O
+secretion	O
+are	O
+dependent	O
+on	O
+estradiol	B-Chemical
+.	O
+
+Hyperprolactinemia	B-Disease
+can	O
+reduce	O
+fertility	O
+and	O
+libido	O
+.	O
+
+Although	O
+central	O
+prolactin	O
+actions	O
+are	O
+thought	O
+to	O
+contribute	O
+to	O
+this	O
+,	O
+the	O
+mechanisms	O
+are	O
+poorly	O
+understood	O
+.	O
+
+We	O
+first	O
+tested	O
+whether	O
+chronic	O
+hyperprolactinemia	B-Disease
+inhibited	O
+two	O
+neuroendocrine	O
+parameters	O
+necessary	O
+for	O
+female	O
+fertility	O
+:	O
+pulsatile	O
+LH	O
+secretion	O
+and	O
+the	O
+estrogen	B-Chemical
+-	O
+induced	O
+LH	O
+surge	O
+.	O
+
+Chronic	O
+hyperprolactinemia	B-Disease
+induced	O
+by	O
+the	O
+dopamine	B-Chemical
+antagonist	O
+sulpiride	B-Chemical
+caused	O
+a	O
+40	O
+%	O
+reduction	O
+LH	O
+pulse	O
+frequency	O
+in	O
+ovariectomized	O
+rats	O
+,	O
+but	O
+only	O
+in	O
+the	O
+presence	O
+of	O
+chronic	O
+low	O
+levels	O
+of	O
+estradiol	B-Chemical
+.	O
+
+Sulpiride	B-Chemical
+did	O
+not	O
+affect	O
+the	O
+magnitude	O
+of	O
+a	O
+steroid	B-Chemical
+-	O
+induced	O
+LH	O
+surge	O
+or	O
+the	O
+percentage	O
+of	O
+GnRH	O
+neurons	O
+activated	O
+during	O
+the	O
+surge	O
+.	O
+
+Estradiol	B-Chemical
+is	O
+known	O
+to	O
+influence	O
+expression	O
+of	O
+the	O
+long	O
+form	O
+of	O
+prolactin	O
+receptors	O
+(	O
+PRL	O
+-	O
+R	O
+)	O
+and	O
+components	O
+of	O
+prolactin	O
+'	O
+s	O
+signaling	O
+pathway	O
+.	O
+
+To	O
+test	O
+the	O
+hypothesis	O
+that	O
+estrogen	B-Chemical
+increases	O
+PRL	O
+-	O
+R	O
+expression	O
+and	O
+sensitivity	O
+to	O
+prolactin	O
+,	O
+we	O
+next	O
+demonstrated	O
+that	O
+estradiol	B-Chemical
+greatly	O
+augments	O
+prolactin	O
+-	O
+induced	O
+STAT5	O
+activation	O
+.	O
+
+Lastly	O
+,	O
+we	O
+measured	O
+PRL	O
+-	O
+R	O
+and	O
+suppressor	O
+of	O
+cytokine	O
+signaling	O
+(	O
+SOCS	O
+-	O
+1	O
+and	O
+-	O
+3	O
+and	O
+CIS	O
+,	O
+which	O
+reflect	O
+the	O
+level	O
+of	O
+prolactin	O
+signaling	O
+)	O
+mRNAs	O
+in	O
+response	O
+to	O
+sulpiride	B-Chemical
+and	O
+estradiol	B-Chemical
+.	O
+
+Sulpiride	B-Chemical
+induced	O
+only	O
+SOCS	O
+-	O
+1	O
+in	O
+the	O
+medial	O
+preoptic	O
+area	O
+,	O
+where	O
+GnRH	O
+neurons	O
+are	O
+regulated	O
+,	O
+but	O
+in	O
+the	O
+arcuate	O
+nucleus	O
+and	O
+choroid	O
+plexus	O
+,	O
+PRL	O
+-	O
+R	O
+,	O
+SOCS	O
+-	O
+3	O
+,	O
+and	O
+CIS	O
+mRNA	O
+levels	O
+were	O
+also	O
+induced	O
+.	O
+
+Estradiol	B-Chemical
+enhanced	O
+these	O
+effects	O
+on	O
+SOCS	O
+-	O
+3	O
+and	O
+CIS	O
+.	O
+
+Interestingly	O
+,	O
+estradiol	B-Chemical
+also	O
+induced	O
+PRL	O
+-	O
+R	O
+,	O
+SOCS	O
+-	O
+3	O
+,	O
+and	O
+CIS	O
+mRNA	O
+levels	O
+independently	O
+.	O
+
+These	O
+data	O
+show	O
+that	O
+GnRH	O
+pulse	O
+frequency	O
+is	O
+inhibited	O
+by	O
+chronic	O
+hyperprolactinemia	B-Disease
+in	O
+a	O
+steroid	B-Chemical
+-	O
+dependent	O
+manner	O
+.	O
+
+They	O
+also	O
+provide	O
+evidence	O
+for	O
+estradiol	B-Chemical
+-	O
+dependent	O
+and	O
+brain	O
+region	O
+-	O
+specific	O
+regulation	O
+of	O
+PRL	O
+-	O
+R	O
+expression	O
+and	O
+signaling	O
+responses	O
+by	O
+prolactin	O
+.	O
+
+Clonidine	B-Chemical
+for	O
+attention	B-Disease
+-	I-Disease
+deficit	I-Disease
+/	I-Disease
+hyperactivity	I-Disease
+disorder	I-Disease
+:	O
+II	O
+.	O
+
+ECG	O
+changes	O
+and	O
+adverse	O
+events	O
+analysis	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+examine	O
+the	O
+safety	O
+and	O
+tolerability	O
+of	O
+clonidine	B-Chemical
+used	O
+alone	O
+or	O
+with	O
+methylphenidate	B-Chemical
+in	O
+children	O
+with	O
+attention	B-Disease
+-	I-Disease
+deficit	I-Disease
+/	I-Disease
+hyperactivity	I-Disease
+disorder	I-Disease
+(	O
+ADHD	B-Disease
+)	O
+.	O
+
+METHOD	O
+:	O
+In	O
+a	O
+16	O
+-	O
+week	O
+multicenter	O
+,	O
+double	O
+-	O
+blind	O
+trial	O
+,	O
+122	O
+children	O
+with	O
+ADHD	B-Disease
+were	O
+randomly	O
+assigned	O
+to	O
+clonidine	B-Chemical
+(	O
+n	O
+=	O
+31	O
+)	O
+,	O
+methylphenidate	B-Chemical
+(	O
+n	O
+=	O
+29	O
+)	O
+,	O
+clonidine	B-Chemical
+and	O
+methylphenidate	B-Chemical
+(	O
+n	O
+=	O
+32	O
+)	O
+,	O
+or	O
+placebo	O
+(	O
+n	O
+=	O
+30	O
+)	O
+.	O
+
+Doses	O
+were	O
+flexibly	O
+titrated	O
+up	O
+to	O
+0	O
+.	O
+6	O
+mg	O
+/	O
+day	O
+for	O
+clonidine	B-Chemical
+and	O
+60	O
+mg	O
+/	O
+day	O
+for	O
+methylphenidate	B-Chemical
+(	O
+both	O
+with	O
+divided	O
+dosing	O
+)	O
+.	O
+
+Groups	O
+were	O
+compared	O
+regarding	O
+adverse	O
+events	O
+and	O
+changes	O
+from	O
+baseline	O
+to	O
+week	O
+16	O
+in	O
+electrocardiograms	O
+and	O
+vital	O
+signs	O
+.	O
+
+RESULTS	O
+:	O
+There	O
+were	O
+more	O
+incidents	O
+of	O
+bradycardia	B-Disease
+in	O
+subjects	O
+treated	O
+with	O
+clonidine	B-Chemical
+compared	O
+with	O
+those	O
+not	O
+treated	O
+with	O
+clonidine	B-Chemical
+(	O
+17	O
+.	O
+5	O
+%	O
+versus	O
+3	O
+.	O
+4	O
+%	O
+;	O
+p	O
+=	O
+.	O
+02	O
+)	O
+,	O
+but	O
+no	O
+other	O
+significant	O
+group	O
+differences	O
+regarding	O
+electrocardiogram	O
+and	O
+other	O
+cardiovascular	O
+outcomes	O
+.	O
+
+There	O
+were	O
+no	O
+suggestions	O
+of	O
+interactions	O
+between	O
+clonidine	B-Chemical
+and	O
+methylphenidate	B-Chemical
+regarding	O
+cardiovascular	O
+outcomes	O
+.	O
+
+Moderate	O
+or	O
+severe	O
+adverse	O
+events	O
+were	O
+more	O
+common	O
+in	O
+subjects	O
+on	O
+clonidine	B-Chemical
+(	O
+79	O
+.	O
+4	O
+%	O
+versus	O
+49	O
+.	O
+2	O
+%	O
+;	O
+p	O
+=	O
+.	O
+0006	O
+)	O
+but	O
+not	O
+associated	O
+with	O
+higher	O
+rates	O
+of	O
+early	O
+study	O
+withdrawal	O
+.	O
+
+Drowsiness	B-Disease
+was	O
+common	O
+on	O
+clonidine	B-Chemical
+,	O
+but	O
+generally	O
+resolved	O
+by	O
+6	O
+to	O
+8	O
+weeks	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Clonidine	B-Chemical
+,	O
+used	O
+alone	O
+or	O
+with	O
+methylphenidate	B-Chemical
+,	O
+appears	O
+safe	O
+and	O
+well	O
+tolerated	O
+in	O
+childhood	O
+ADHD	B-Disease
+.	O
+
+Physicians	O
+prescribing	O
+clonidine	B-Chemical
+should	O
+monitor	O
+for	O
+bradycardia	B-Disease
+and	O
+advise	O
+patients	O
+about	O
+the	O
+high	O
+likelihood	O
+of	O
+initial	O
+drowsiness	B-Disease
+.	O
+
+Renal	B-Disease
+Fanconi	I-Disease
+syndrome	I-Disease
+and	O
+myopathy	B-Disease
+after	O
+liver	O
+transplantation	O
+:	O
+drug	O
+-	O
+related	O
+mitochondrial	B-Disease
+cytopathy	I-Disease
+?	O
+
+Advances	O
+in	O
+the	O
+field	O
+of	O
+transplantation	O
+provide	O
+a	O
+better	O
+quality	O
+of	O
+life	O
+and	O
+allow	O
+more	O
+favorable	O
+conditions	O
+for	O
+growth	O
+and	O
+development	O
+in	O
+children	O
+.	O
+
+However	O
+,	O
+combinations	O
+of	O
+different	O
+therapeutic	O
+regimens	O
+require	O
+consideration	O
+of	O
+potential	O
+adverse	O
+reactions	O
+.	O
+
+We	O
+describe	O
+a	O
+15	O
+-	O
+yr	O
+-	O
+old	O
+girl	O
+who	O
+had	O
+orthotopic	O
+liver	O
+transplantation	O
+because	O
+of	O
+Wilson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+Tacrolimus	B-Chemical
+,	O
+MMF	B-Chemical
+,	O
+and	O
+steroids	B-Chemical
+were	O
+given	O
+as	O
+immunosuppressant	O
+.	O
+
+Lamivudine	B-Chemical
+was	O
+added	O
+because	O
+of	O
+de	O
+nova	O
+hepatitis	B-Disease
+B	I-Disease
+infection	I-Disease
+during	O
+her	O
+follow	O
+-	O
+up	O
+.	O
+
+Three	O
+yr	O
+after	O
+transplantation	O
+she	O
+developed	O
+renal	B-Disease
+Fanconi	I-Disease
+syndrome	I-Disease
+with	O
+severe	O
+metabolic	B-Disease
+acidosis	I-Disease
+,	O
+hypophosphatemia	B-Disease
+,	O
+glycosuria	B-Disease
+,	O
+and	O
+aminoaciduria	B-Disease
+.	O
+
+Although	O
+tacrolimus	B-Chemical
+was	O
+suspected	O
+to	O
+be	O
+the	O
+cause	O
+of	O
+late	O
+post	O
+-	O
+transplant	O
+renal	O
+acidosis	B-Disease
+and	O
+was	O
+replaced	O
+by	O
+sirolimus	B-Chemical
+,	O
+acidosis	B-Disease
+,	O
+and	O
+electrolyte	O
+imbalance	O
+got	O
+worse	O
+.	O
+
+Proximal	O
+muscle	B-Disease
+weakness	I-Disease
+has	O
+developed	O
+during	O
+her	O
+follow	O
+-	O
+up	O
+.	O
+
+Fanconi	B-Disease
+syndrome	I-Disease
+,	O
+as	O
+well	O
+as	O
+myopathy	B-Disease
+,	O
+is	O
+well	O
+recognized	O
+in	O
+patients	O
+with	O
+mitochondrial	B-Disease
+disorders	I-Disease
+and	O
+caused	O
+by	O
+depletion	O
+of	O
+mtDNA	O
+.	O
+
+We	O
+suggest	O
+that	O
+our	O
+patient	O
+'	O
+s	O
+tubular	B-Disease
+dysfunction	I-Disease
+and	O
+myopathy	B-Disease
+may	O
+have	O
+resulted	O
+from	O
+mitochondrial	B-Disease
+dysfunction	I-Disease
+which	O
+is	O
+triggered	O
+by	O
+tacrolimus	B-Chemical
+and	O
+augmented	O
+by	O
+lamivudine	B-Chemical
+.	O
+
+Higher	O
+optical	O
+density	O
+of	O
+an	O
+antigen	O
+assay	O
+predicts	O
+thrombosis	B-Disease
+in	O
+patients	O
+with	O
+heparin	B-Chemical
+-	O
+induced	O
+thrombocytopenia	B-Disease
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+correlate	O
+optical	O
+density	O
+and	O
+percent	O
+inhibition	O
+of	O
+a	O
+two	O
+-	O
+step	O
+heparin	B-Chemical
+-	O
+induced	O
+thrombocytopenia	B-Disease
+(	O
+HIT	B-Disease
+)	O
+antigen	O
+assay	O
+with	O
+thrombosis	B-Disease
+;	O
+the	O
+assay	O
+utilizes	O
+reaction	O
+inhibition	O
+characteristics	O
+of	O
+a	O
+high	O
+heparin	B-Chemical
+concentration	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Patients	O
+with	O
+more	O
+than	O
+50	O
+%	O
+decrease	O
+in	O
+platelet	O
+count	O
+or	O
+thrombocytopenia	B-Disease
+(	O
+<	O
+150	O
+x	O
+10	O
+(	O
+9	O
+)	O
+/	O
+L	O
+)	O
+after	O
+exposure	O
+to	O
+heparin	B-Chemical
+,	O
+who	O
+had	O
+a	O
+positive	O
+two	O
+-	O
+step	O
+antigen	O
+assay	O
+[	O
+optical	O
+density	O
+(	O
+OD	O
+)	O
+>	O
+0	O
+.	O
+4	O
+and	O
+>	O
+50	O
+inhibition	O
+with	O
+high	O
+concentration	O
+of	O
+heparin	B-Chemical
+]	O
+were	O
+included	O
+in	O
+the	O
+study	O
+.	O
+
+RESULTS	O
+:	O
+Forty	O
+of	O
+94	O
+HIT	B-Disease
+patients	O
+had	O
+thrombosis	B-Disease
+at	O
+diagnosis	O
+;	O
+54	O
+/	O
+94	O
+had	O
+isolated	O
+-	O
+HIT	B-Disease
+without	O
+thrombosis	B-Disease
+.	O
+
+Eight	O
+of	O
+the	O
+isolated	O
+-	O
+HIT	B-Disease
+patients	O
+developed	O
+thrombosis	B-Disease
+within	O
+the	O
+next	O
+30	O
+d	O
+;	O
+thus	O
+,	O
+a	O
+total	O
+of	O
+48	O
+patients	O
+had	O
+thrombosis	B-Disease
+at	O
+day	O
+30	O
+.	O
+
+At	O
+diagnosis	O
+there	O
+was	O
+no	O
+significant	O
+difference	O
+in	O
+OD	O
+between	O
+HIT	B-Disease
+patients	O
+with	O
+thrombosis	B-Disease
+and	O
+those	O
+with	O
+isolated	O
+-	O
+HIT	B-Disease
+.	O
+
+However	O
+,	O
+OD	O
+was	O
+significantly	O
+higher	O
+in	O
+all	O
+patients	O
+with	O
+thrombosis	B-Disease
+(	O
+n	O
+=	O
+48	O
+,	O
+1	O
+.	O
+34	O
++	O
+/	O
+-	O
+0	O
+.	O
+89	O
+)	O
+,	O
+including	O
+isolated	O
+-	O
+HIT	B-Disease
+patients	O
+who	O
+later	O
+developed	O
+thrombosis	B-Disease
+within	O
+30	O
+d	O
+(	O
+n	O
+=	O
+8	O
+,	O
+1	O
+.	O
+84	O
++	O
+/	O
+-	O
+0	O
+.	O
+64	O
+)	O
+as	O
+compared	O
+to	O
+isolated	O
+-	O
+HIT	B-Disease
+patients	O
+who	O
+did	O
+not	O
+develop	O
+thrombosis	B-Disease
+(	O
+0	O
+.	O
+96	O
++	O
+/	O
+-	O
+0	O
+.	O
+75	O
+;	O
+P	O
+=	O
+0	O
+.	O
+011	O
+and	O
+P	O
+=	O
+0	O
+.	O
+008	O
+)	O
+.	O
+
+The	O
+Receiver	O
+Operative	O
+Characteristic	O
+Curve	O
+showed	O
+that	O
+OD	O
+>	O
+1	O
+.	O
+27	O
+in	O
+the	O
+isolated	O
+-	O
+HIT	B-Disease
+group	O
+had	O
+a	O
+significantly	O
+higher	O
+chance	O
+of	O
+developing	O
+thrombosis	B-Disease
+by	O
+day	O
+30	O
+.	O
+
+None	O
+of	O
+these	O
+groups	O
+showed	O
+significant	O
+difference	O
+in	O
+percent	O
+inhibition	O
+.	O
+
+Multivariate	O
+analysis	O
+showed	O
+a	O
+2	O
+.	O
+8	O
+-	O
+fold	O
+increased	O
+risk	O
+of	O
+thrombosis	B-Disease
+in	O
+females	O
+.	O
+
+Similarly	O
+,	O
+thrombotic	B-Disease
+risk	O
+increased	O
+with	O
+age	O
+and	O
+OD	O
+values	O
+.	O
+
+CONCLUSION	O
+:	O
+Higher	O
+OD	O
+is	O
+associated	O
+with	O
+significant	O
+risk	O
+of	O
+subsequent	O
+thrombosis	B-Disease
+in	O
+patients	O
+with	O
+isolated	O
+-	O
+HIT	B-Disease
+;	O
+percent	O
+inhibition	O
+,	O
+however	O
+,	O
+was	O
+not	O
+predictive	O
+.	O
+
+Thalidomide	B-Chemical
+has	O
+limited	O
+single	O
+-	O
+agent	O
+activity	O
+in	O
+relapsed	O
+or	O
+refractory	O
+indolent	O
+non	B-Disease
+-	I-Disease
+Hodgkin	I-Disease
+lymphomas	I-Disease
+:	O
+a	O
+phase	O
+II	O
+trial	O
+of	O
+the	O
+Cancer	B-Disease
+and	O
+Leukemia	B-Disease
+Group	O
+B	O
+.	O
+
+Thalidomide	B-Chemical
+is	O
+an	O
+immunomodulatory	O
+agent	O
+with	O
+demonstrated	O
+activity	O
+in	O
+multiple	B-Disease
+myeloma	I-Disease
+,	O
+mantle	B-Disease
+cell	I-Disease
+lymphoma	I-Disease
+and	O
+lymphoplasmacytic	B-Disease
+lymphoma	I-Disease
+.	O
+
+Its	O
+activity	O
+is	O
+believed	O
+to	O
+be	O
+due	O
+modulation	O
+of	O
+the	O
+tumour	B-Disease
+milieu	O
+,	O
+including	O
+downregulation	O
+of	O
+angiogenesis	O
+and	O
+inflammatory	O
+cytokines	O
+.	O
+
+Between	O
+July	O
+2001	O
+and	O
+April	O
+2004	O
+,	O
+24	O
+patients	O
+with	O
+relapsed	O
+/	O
+refractory	O
+indolent	O
+lymphomas	B-Disease
+received	O
+thalidomide	B-Chemical
+200	O
+mg	O
+daily	O
+with	O
+escalation	O
+by	O
+100	O
+mg	O
+daily	O
+every	O
+1	O
+-	O
+2	O
+weeks	O
+as	O
+tolerated	O
+,	O
+up	O
+to	O
+a	O
+maximum	O
+of	O
+800	O
+mg	O
+daily	O
+.	O
+
+Patients	O
+had	O
+received	O
+a	O
+median	O
+of	O
+2	O
+(	O
+range	O
+,	O
+1	O
+-	O
+4	O
+)	O
+prior	O
+regimens	O
+.	O
+
+Of	O
+24	O
+evaluable	O
+patients	O
+,	O
+two	O
+achieved	O
+a	O
+complete	O
+remission	O
+and	O
+one	O
+achieved	O
+a	O
+partial	O
+remission	O
+for	O
+an	O
+overall	O
+response	O
+rate	O
+of	O
+12	O
+.	O
+5	O
+%	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+:	O
+2	O
+.	O
+6	O
+-	O
+32	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+Eleven	O
+patients	O
+progressed	O
+during	O
+therapy	O
+.	O
+
+Grade	O
+3	O
+-	O
+4	O
+adverse	O
+effects	O
+included	O
+myelosuppression	B-Disease
+,	O
+fatigue	B-Disease
+,	O
+somnolence	B-Disease
+/	O
+depressed	B-Disease
+mood	I-Disease
+,	O
+neuropathy	B-Disease
+and	O
+dyspnea	B-Disease
+.	O
+
+Of	O
+concern	O
+was	O
+the	O
+occurrence	O
+of	O
+four	O
+thromboembolic	B-Disease
+events	O
+.	O
+
+Our	O
+results	O
+failed	O
+to	O
+demonstrate	O
+an	O
+important	O
+response	O
+rate	O
+to	O
+single	O
+agent	O
+thalidomide	B-Chemical
+in	O
+indolent	O
+lymphomas	B-Disease
+and	O
+contrast	O
+with	O
+the	O
+higher	O
+activity	O
+level	O
+reported	O
+with	O
+the	O
+second	O
+generation	O
+immunomodulatory	O
+agent	O
+,	O
+lenalidomide	B-Chemical
+.	O
+
+Sex	O
+differences	O
+in	O
+NMDA	B-Chemical
+antagonist	O
+enhancement	O
+of	O
+morphine	B-Chemical
+antihyperalgesia	O
+in	O
+a	O
+capsaicin	B-Chemical
+model	O
+of	O
+persistent	O
+pain	B-Disease
+:	O
+comparisons	O
+to	O
+two	O
+models	O
+of	O
+acute	B-Disease
+pain	I-Disease
+.	O
+
+In	O
+acute	B-Disease
+pain	I-Disease
+models	O
+,	O
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+D	I-Chemical
+-	I-Chemical
+aspartate	I-Chemical
+(	O
+NMDA	B-Chemical
+)	O
+antagonists	O
+enhance	O
+the	O
+antinociceptive	O
+effects	O
+of	O
+morphine	B-Chemical
+to	O
+a	O
+greater	O
+extent	O
+in	O
+males	O
+than	O
+females	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+investigation	O
+was	O
+to	O
+extend	O
+these	O
+findings	O
+to	O
+a	O
+persistent	O
+pain	B-Disease
+model	O
+which	O
+could	O
+be	O
+distinguished	O
+from	O
+acute	B-Disease
+pain	I-Disease
+models	O
+on	O
+the	O
+basis	O
+of	O
+the	O
+nociceptive	O
+fibers	O
+activated	O
+,	O
+neurochemical	O
+substrates	O
+,	O
+and	O
+duration	O
+of	O
+the	O
+nociceptive	O
+stimulus	O
+.	O
+
+To	O
+this	O
+end	O
+,	O
+persistent	O
+hyperalgesia	B-Disease
+was	O
+induced	O
+by	O
+administration	O
+of	O
+capsaicin	B-Chemical
+in	O
+the	O
+tail	O
+of	O
+gonadally	O
+intact	O
+F344	O
+rats	O
+,	O
+following	O
+which	O
+the	O
+tail	O
+was	O
+immersed	O
+in	O
+a	O
+mildly	O
+noxious	O
+thermal	O
+stimulus	O
+,	O
+and	O
+tail	O
+-	O
+withdrawal	O
+latencies	O
+measured	O
+.	O
+
+For	O
+comparison	O
+,	O
+tests	O
+were	O
+conducted	O
+in	O
+two	O
+acute	B-Disease
+pain	I-Disease
+models	O
+,	O
+the	O
+hotplate	O
+and	O
+warm	O
+water	O
+tail	O
+-	O
+withdrawal	O
+procedures	O
+.	O
+
+In	O
+males	O
+,	O
+the	O
+non	O
+-	O
+competitive	O
+NMDA	B-Chemical
+antagonist	O
+dextromethorphan	B-Chemical
+enhanced	O
+the	O
+antihyperalgesic	O
+effect	O
+of	O
+low	O
+to	O
+moderate	O
+doses	O
+of	O
+morphine	B-Chemical
+in	O
+a	O
+dose	O
+-	O
+and	O
+time	O
+-	O
+dependent	O
+manner	O
+.	O
+
+Across	O
+the	O
+doses	O
+and	O
+pretreatment	O
+times	O
+examined	O
+,	O
+enhancement	O
+was	O
+not	O
+observed	O
+in	O
+females	O
+.	O
+
+Enhancement	O
+of	O
+morphine	B-Chemical
+antinociception	O
+by	O
+dextromethorphan	B-Chemical
+was	O
+seen	O
+in	O
+both	O
+males	O
+and	O
+females	O
+in	O
+the	O
+acute	B-Disease
+pain	I-Disease
+models	O
+,	O
+with	O
+the	O
+magnitude	O
+of	O
+this	O
+effect	O
+being	O
+greater	O
+in	O
+males	O
+.	O
+
+These	O
+findings	O
+demonstrate	O
+a	O
+sexually	O
+-	O
+dimorphic	O
+interaction	O
+between	O
+NMDA	B-Chemical
+antagonists	O
+and	O
+morphine	B-Chemical
+in	O
+a	O
+persistent	O
+pain	B-Disease
+model	O
+that	O
+can	O
+be	O
+distinguished	O
+from	O
+those	O
+observed	O
+in	O
+acute	B-Disease
+pain	I-Disease
+models	O
+.	O
+
+Development	O
+of	O
+proteinuria	B-Disease
+after	O
+switch	O
+to	O
+sirolimus	B-Chemical
+-	O
+based	O
+immunosuppression	O
+in	O
+long	O
+-	O
+term	O
+cardiac	O
+transplant	O
+patients	O
+.	O
+
+Calcineurin	O
+-	O
+inhibitor	O
+therapy	O
+can	O
+lead	O
+to	O
+renal	B-Disease
+dysfunction	I-Disease
+in	O
+heart	O
+transplantation	O
+patients	O
+.	O
+
+The	O
+novel	O
+immunosuppressive	O
+(	O
+IS	O
+)	O
+drug	O
+sirolmus	B-Chemical
+(	O
+Srl	B-Chemical
+)	O
+lacks	O
+nephrotoxic	B-Disease
+effects	O
+;	O
+however	O
+,	O
+proteinuria	B-Disease
+associated	O
+with	O
+Srl	B-Chemical
+has	O
+been	O
+reported	O
+following	O
+renal	O
+transplantation	O
+.	O
+
+In	O
+cardiac	O
+transplantation	O
+,	O
+the	O
+incidence	O
+of	O
+proteinuria	B-Disease
+associated	O
+with	O
+Srl	B-Chemical
+is	O
+unknown	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+long	O
+-	O
+term	O
+cardiac	O
+transplant	O
+patients	O
+were	O
+switched	O
+from	O
+cyclosporine	B-Chemical
+to	O
+Srl	B-Chemical
+-	O
+based	O
+IS	O
+.	O
+
+Concomitant	O
+IS	O
+consisted	O
+of	O
+mycophenolate	B-Chemical
+mofetil	I-Chemical
++	O
+/	O
+-	O
+steroids	B-Chemical
+.	O
+
+Proteinuria	O
+increased	O
+significantly	O
+from	O
+a	O
+median	O
+of	O
+0	O
+.	O
+13	O
+g	O
+/	O
+day	O
+(	O
+range	O
+0	O
+-	O
+5	O
+.	O
+7	O
+)	O
+preswitch	O
+to	O
+0	O
+.	O
+23	O
+g	O
+/	O
+day	O
+(	O
+0	O
+-	O
+9	O
+.	O
+88	O
+)	O
+at	O
+24	O
+months	O
+postswitch	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0024	O
+)	O
+.	O
+
+Before	O
+the	O
+switch	O
+,	O
+11	O
+.	O
+5	O
+%	O
+of	O
+patients	O
+had	O
+high	O
+-	O
+grade	O
+proteinuria	B-Disease
+(	O
+>	O
+1	O
+.	O
+0	O
+g	O
+/	O
+day	O
+)	O
+;	O
+this	O
+increased	O
+to	O
+22	O
+.	O
+9	O
+%	O
+postswitch	O
+(	O
+p	O
+=	O
+0	O
+.	O
+006	O
+)	O
+.	O
+
+ACE	B-Chemical
+inhibitor	I-Chemical
+and	O
+angiotensin	B-Chemical
+-	I-Chemical
+releasing	I-Chemical
+blocker	I-Chemical
+(	O
+ARB	B-Chemical
+)	O
+therapy	O
+reduced	O
+proteinuria	B-Disease
+development	O
+.	O
+
+Patients	O
+without	O
+proteinuria	B-Disease
+had	O
+increased	O
+renal	O
+function	O
+(	O
+median	O
+42	O
+.	O
+5	O
+vs	O
+.	O
+64	O
+.	O
+1	O
+,	O
+p	O
+=	O
+0	O
+.	O
+25	O
+)	O
+,	O
+whereas	O
+patients	O
+who	O
+developed	O
+high	O
+-	O
+grade	O
+proteinuria	B-Disease
+showed	O
+decreased	O
+renal	O
+function	O
+at	O
+the	O
+end	O
+of	O
+follow	O
+-	O
+up	O
+(	O
+median	O
+39	O
+.	O
+6	O
+vs	O
+.	O
+29	O
+.	O
+2	O
+,	O
+p	O
+=	O
+0	O
+.	O
+125	O
+)	O
+.	O
+
+Thus	O
+,	O
+proteinuria	B-Disease
+may	O
+develop	O
+in	O
+cardiac	O
+transplant	O
+patients	O
+after	O
+switch	O
+to	O
+Srl	B-Chemical
+,	O
+which	O
+may	O
+have	O
+an	O
+adverse	O
+effect	O
+on	O
+renal	O
+function	O
+in	O
+these	O
+patients	O
+.	O
+
+Srl	B-Chemical
+should	O
+be	O
+used	O
+with	O
+ACEi	B-Chemical
+/	O
+ARB	B-Chemical
+therapy	O
+and	O
+patients	O
+monitored	O
+for	O
+proteinuria	B-Disease
+and	O
+increased	O
+renal	B-Disease
+dysfunction	I-Disease
+.	O
+
+Ginsenoside	B-Chemical
+Rg1	I-Chemical
+restores	O
+the	O
+impairment	B-Disease
+of	I-Disease
+learning	I-Disease
+induced	O
+by	O
+chronic	O
+morphine	B-Chemical
+administration	O
+in	O
+rats	O
+.	O
+
+Rg1	B-Chemical
+,	O
+as	O
+a	O
+ginsenoside	B-Chemical
+extracted	O
+from	O
+Panax	O
+ginseng	O
+,	O
+could	O
+ameliorate	O
+spatial	O
+learning	B-Disease
+impairment	I-Disease
+.	O
+
+Previous	O
+studies	O
+have	O
+demonstrated	O
+that	O
+Rg1	B-Chemical
+might	O
+be	O
+a	O
+useful	O
+agent	O
+for	O
+the	O
+prevention	O
+and	O
+treatment	O
+of	O
+the	O
+adverse	O
+effects	O
+of	O
+morphine	B-Chemical
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+the	O
+effect	O
+of	O
+Rg1	B-Chemical
+on	O
+learning	B-Disease
+impairment	I-Disease
+by	O
+chronic	O
+morphine	B-Chemical
+administration	O
+and	O
+the	O
+mechanism	O
+responsible	O
+for	O
+this	O
+effect	O
+.	O
+
+Male	O
+rats	O
+were	O
+subcutaneously	O
+injected	O
+with	O
+morphine	B-Chemical
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+twice	O
+a	O
+day	O
+at	O
+12	O
+hour	O
+intervals	O
+for	O
+10	O
+days	O
+,	O
+and	O
+Rg1	B-Chemical
+(	O
+30	O
+mg	O
+/	O
+kg	O
+)	O
+was	O
+intraperitoneally	O
+injected	O
+2	O
+hours	O
+after	O
+the	O
+second	O
+injection	O
+of	O
+morphine	B-Chemical
+once	O
+a	O
+day	O
+for	O
+10	O
+days	O
+.	O
+
+Spatial	O
+learning	O
+capacity	O
+was	O
+assessed	O
+in	O
+the	O
+Morris	O
+water	O
+maze	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+rats	O
+treated	O
+with	O
+Morphine	B-Chemical
+/	O
+Rg1	B-Chemical
+decreased	O
+escape	O
+latency	O
+and	O
+increased	O
+the	O
+time	O
+spent	O
+in	O
+platform	O
+quadrant	O
+and	O
+entering	O
+frequency	O
+.	O
+
+By	O
+implantation	O
+of	O
+electrodes	O
+and	O
+electrophysiological	O
+recording	O
+in	O
+vivo	O
+,	O
+the	O
+results	O
+showed	O
+that	O
+Rg1	B-Chemical
+restored	O
+the	O
+long	O
+-	O
+term	O
+potentiation	O
+(	O
+LTP	O
+)	O
+impaired	O
+by	O
+morphine	B-Chemical
+in	O
+both	O
+freely	O
+moving	O
+and	O
+anaesthetised	O
+rats	O
+.	O
+
+The	O
+electrophysiological	O
+recording	O
+in	O
+vitro	O
+showed	O
+that	O
+Rg1	B-Chemical
+restored	O
+the	O
+LTP	O
+in	O
+slices	O
+from	O
+the	O
+rats	O
+treated	O
+with	O
+morphine	B-Chemical
+,	O
+but	O
+not	O
+changed	O
+LTP	O
+in	O
+the	O
+slices	O
+from	O
+normal	O
+saline	O
+-	O
+or	O
+morphine	B-Chemical
+/	O
+Rg1	B-Chemical
+-	O
+treated	O
+rats	O
+;	O
+this	O
+restoration	O
+could	O
+be	O
+inhibited	O
+by	O
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+D	I-Chemical
+-	I-Chemical
+aspartate	I-Chemical
+(	O
+NMDA	B-Chemical
+)	O
+receptor	O
+antagonist	O
+MK801	B-Chemical
+.	O
+
+We	O
+conclude	O
+that	O
+Rg1	B-Chemical
+may	O
+significantly	O
+improve	O
+the	O
+spatial	O
+learning	O
+capacity	O
+impaired	O
+by	O
+chonic	O
+morphine	B-Chemical
+administration	O
+and	O
+restore	O
+the	O
+morphine	B-Chemical
+-	O
+inhibited	O
+LTP	O
+.	O
+
+This	O
+effect	O
+is	O
+NMDA	B-Chemical
+receptor	O
+dependent	O
+.	O
+
+Synthesis	O
+of	O
+N	B-Chemical
+-	I-Chemical
+pyrimidinyl	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+phenoxyacetamides	I-Chemical
+as	O
+adenosine	B-Chemical
+A2A	O
+receptor	O
+antagonists	O
+.	O
+
+A	O
+series	O
+of	O
+N	B-Chemical
+-	I-Chemical
+pyrimidinyl	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+phenoxyacetamide	I-Chemical
+adenosine	B-Chemical
+A	O
+(	O
+2A	O
+)	O
+antagonists	O
+is	O
+described	O
+.	O
+
+SAR	O
+studies	O
+led	O
+to	O
+compound	O
+14	O
+with	O
+excellent	O
+potency	O
+(	O
+K	O
+(	O
+i	O
+)	O
+=	O
+0	O
+.	O
+4	O
+nM	O
+)	O
+,	O
+selectivity	O
+(	O
+A	O
+(	O
+1	O
+)	O
+/	O
+A	O
+(	O
+2A	O
+)	O
+>	O
+100	O
+)	O
+,	O
+and	O
+efficacy	O
+(	O
+MED	O
+10	O
+mg	O
+/	O
+kg	O
+p	O
+.	O
+o	O
+.	O
+)	O
+in	O
+the	O
+rat	O
+haloperidol	B-Chemical
+-	O
+induced	O
+catalepsy	B-Disease
+model	O
+for	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+Evidence	O
+for	O
+an	O
+involvement	O
+of	O
+D1	O
+and	O
+D2	O
+dopamine	B-Chemical
+receptors	O
+in	O
+mediating	O
+nicotine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+in	O
+rats	O
+.	O
+
+Previous	O
+studies	O
+have	O
+suggested	O
+that	O
+repeated	O
+exposure	O
+of	O
+rats	O
+to	O
+the	O
+drug	O
+or	O
+to	O
+the	O
+experimental	O
+environment	O
+is	O
+necessary	O
+to	O
+observe	O
+nicotine	B-Chemical
+-	O
+induced	O
+locomotor	O
+stimulation	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+the	O
+role	O
+of	O
+habituation	O
+to	O
+the	O
+experimental	O
+environment	O
+on	O
+the	O
+stimulant	O
+effect	O
+of	O
+nicotine	B-Chemical
+in	O
+rats	O
+was	O
+examined	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+role	O
+of	O
+dopamine	B-Chemical
+receptors	O
+in	O
+mediating	O
+nicotine	B-Chemical
+-	O
+induced	O
+locomotor	O
+stimulation	O
+was	O
+investigated	O
+by	O
+examining	O
+the	O
+effects	O
+of	O
+selective	O
+D1	O
+and	O
+D2	O
+dopamine	B-Chemical
+receptor	O
+antagonists	O
+on	O
+activity	O
+induced	O
+by	O
+nicotine	B-Chemical
+.	O
+
+Locomotor	O
+activity	O
+was	O
+assessed	O
+in	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+tested	O
+in	O
+photocell	O
+cages	O
+.	O
+
+Nicotine	B-Chemical
+(	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+)	O
+caused	O
+a	O
+significant	O
+increase	B-Disease
+in	I-Disease
+locomotor	I-Disease
+activity	I-Disease
+in	O
+rats	O
+that	O
+were	O
+habituated	O
+to	O
+the	O
+test	O
+environment	O
+,	O
+but	O
+had	O
+only	O
+a	O
+weak	O
+and	O
+delayed	O
+stimulant	O
+action	O
+in	O
+rats	O
+that	O
+were	O
+unfamiliar	O
+with	O
+the	O
+test	O
+environment	O
+.	O
+
+The	O
+stimulant	O
+action	O
+of	O
+nicotine	B-Chemical
+was	O
+blocked	O
+by	O
+the	O
+central	O
+nicotinic	O
+antagonist	O
+mecamylamine	B-Chemical
+but	O
+not	O
+by	O
+the	O
+peripheral	O
+nicotinic	O
+blocker	O
+hexamethonium	B-Chemical
+,	O
+indicating	O
+that	O
+the	O
+response	O
+is	O
+probably	O
+mediated	O
+by	O
+central	O
+nicotinic	O
+receptors	O
+.	O
+
+Nicotine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+was	O
+blocked	O
+by	O
+the	O
+selective	O
+D1	O
+antagonist	O
+SCH	B-Chemical
+23390	I-Chemical
+,	O
+the	O
+selective	O
+D2	O
+antagonist	O
+raclopride	B-Chemical
+and	O
+the	O
+D1	O
+/	O
+D2	O
+antagonist	O
+fluphenazine	B-Chemical
+.	O
+
+Pretreatment	O
+with	O
+the	O
+D2	O
+agonist	O
+PHNO	B-Chemical
+enhanced	O
+nicotine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+,	O
+whereas	O
+the	O
+D1	O
+agonist	O
+SKF	B-Chemical
+38393	I-Chemical
+had	O
+no	O
+effect	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+acute	O
+nicotine	B-Chemical
+injection	O
+induces	O
+a	O
+pronounced	O
+hyperactivity	B-Disease
+in	O
+rats	O
+habituated	O
+to	O
+the	O
+test	O
+environment	O
+.	O
+
+The	O
+effect	O
+appears	O
+to	O
+be	O
+mediated	O
+by	O
+central	O
+nicotine	B-Chemical
+receptors	O
+,	O
+possibly	O
+located	O
+on	O
+dopaminergic	O
+neurons	O
+,	O
+and	O
+also	O
+requires	O
+the	O
+activation	O
+of	O
+both	O
+D1	O
+and	O
+D2	O
+dopamine	B-Chemical
+receptors	O
+.	O
+
+Central	O
+retinal	B-Disease
+vein	I-Disease
+occlusion	I-Disease
+associated	O
+with	O
+clomiphene	B-Chemical
+-	O
+induced	O
+ovulation	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+report	O
+a	O
+case	O
+of	O
+central	O
+retinal	B-Disease
+vein	I-Disease
+occlusion	I-Disease
+associated	O
+with	O
+clomiphene	B-Chemical
+citrate	I-Chemical
+(	O
+CC	B-Chemical
+)	O
+.	O
+
+DESIGN	O
+:	O
+Case	O
+study	O
+.	O
+
+SETTING	O
+:	O
+Ophthalmology	O
+clinic	O
+of	O
+an	O
+academic	O
+hospital	O
+.	O
+
+PATIENT	O
+(	O
+S	O
+)	O
+:	O
+A	O
+36	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+referred	O
+from	O
+the	O
+infertility	B-Disease
+clinic	O
+for	O
+blurred	B-Disease
+vision	I-Disease
+.	O
+
+INTERVENTION	O
+(	O
+S	O
+)	O
+:	O
+Ophthalmic	O
+examination	O
+after	O
+CC	B-Chemical
+therapy	O
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURE	O
+(	O
+S	O
+)	O
+:	O
+Central	O
+retinal	B-Disease
+vein	I-Disease
+occlusion	I-Disease
+after	O
+ovulation	O
+induction	O
+with	O
+CC	B-Chemical
+.	O
+
+RESULT	O
+(	O
+S	O
+)	O
+:	O
+A	O
+36	O
+-	O
+year	O
+-	O
+old	O
+Chinese	O
+woman	O
+developed	O
+central	O
+retinal	B-Disease
+vein	I-Disease
+occlusion	I-Disease
+after	O
+eight	O
+courses	O
+of	O
+CC	B-Chemical
+.	O
+
+A	O
+search	O
+of	O
+the	O
+literature	O
+on	O
+the	O
+thromboembolic	B-Disease
+complications	O
+of	O
+CC	B-Chemical
+does	O
+not	O
+include	O
+this	O
+severe	O
+ophthalmic	O
+complication	O
+,	O
+although	O
+mild	O
+visual	B-Disease
+disturbance	I-Disease
+after	O
+CC	B-Chemical
+intake	O
+is	O
+not	O
+uncommon	O
+.	O
+
+CONCLUSION	O
+(	O
+S	O
+)	O
+:	O
+This	O
+is	O
+the	O
+first	O
+reported	O
+case	O
+of	O
+central	O
+retinal	B-Disease
+vein	I-Disease
+occlusion	I-Disease
+after	O
+treatment	O
+with	O
+CC	B-Chemical
+.	O
+
+Extra	O
+caution	O
+is	O
+warranted	O
+in	O
+treating	O
+infertility	B-Disease
+patients	O
+with	O
+CC	B-Chemical
+,	O
+and	O
+patients	O
+should	O
+be	O
+well	O
+informed	O
+of	O
+this	O
+side	O
+effect	O
+before	O
+commencement	O
+of	O
+therapy	O
+.	O
+
+Acute	O
+bronchodilating	O
+effects	O
+of	O
+ipratropium	B-Chemical
+bromide	I-Chemical
+and	O
+theophylline	B-Chemical
+in	O
+chronic	B-Disease
+obstructive	I-Disease
+pulmonary	I-Disease
+disease	I-Disease
+.	O
+
+The	O
+bronchodilator	O
+effects	O
+of	O
+a	O
+single	O
+dose	O
+of	O
+ipratropium	B-Chemical
+bromide	I-Chemical
+aerosol	O
+(	O
+36	O
+micrograms	O
+)	O
+and	O
+short	O
+-	O
+acting	O
+theophylline	B-Chemical
+tablets	O
+(	O
+dose	O
+titrated	O
+to	O
+produce	O
+serum	O
+levels	O
+of	O
+10	O
+-	O
+20	O
+micrograms	O
+/	O
+mL	O
+)	O
+were	O
+compared	O
+in	O
+a	O
+double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+crossover	O
+study	O
+in	O
+21	O
+patients	O
+with	O
+stable	O
+,	O
+chronic	B-Disease
+obstructive	I-Disease
+pulmonary	I-Disease
+disease	I-Disease
+.	O
+
+Mean	O
+peak	O
+forced	O
+expiratory	O
+volume	O
+in	O
+1	O
+second	O
+(	O
+FEV1	O
+)	O
+increases	O
+over	O
+baseline	O
+and	O
+the	O
+proportion	O
+of	O
+patients	O
+attaining	O
+at	O
+least	O
+a	O
+15	O
+%	O
+increase	O
+in	O
+the	O
+FEV1	O
+(	O
+responders	O
+)	O
+were	O
+31	O
+%	O
+and	O
+90	O
+%	O
+,	O
+respectively	O
+,	O
+for	O
+ipratropium	B-Chemical
+and	O
+17	O
+%	O
+and	O
+50	O
+%	O
+,	O
+respectively	O
+,	O
+for	O
+theophylline	B-Chemical
+.	O
+
+The	O
+average	O
+FEV1	O
+increases	O
+during	O
+the	O
+6	O
+-	O
+hour	O
+observation	O
+period	O
+were	O
+18	O
+%	O
+for	O
+ipratropium	B-Chemical
+and	O
+8	O
+%	O
+for	O
+theophylline	B-Chemical
+.	O
+
+The	O
+mean	O
+duration	O
+of	O
+action	O
+was	O
+3	O
+.	O
+8	O
+hours	O
+with	O
+ipratropium	B-Chemical
+and	O
+2	O
+.	O
+4	O
+hours	O
+with	O
+theophylline	B-Chemical
+.	O
+
+While	O
+side	O
+effects	O
+were	O
+rare	O
+,	O
+those	O
+experienced	O
+after	O
+theophylline	B-Chemical
+use	O
+did	O
+involve	O
+the	O
+cardiovascular	B-Disease
+and	I-Disease
+gastrointestinal	I-Disease
+systems	I-Disease
+.	O
+
+These	O
+results	O
+show	O
+that	O
+ipratropium	B-Chemical
+is	O
+a	O
+more	O
+potent	O
+bronchodilator	O
+than	O
+oral	O
+theophylline	B-Chemical
+in	O
+patients	O
+with	O
+chronic	B-Disease
+airflow	I-Disease
+obstruction	I-Disease
+.	O
+
+Methamphetamine	B-Chemical
+-	O
+induced	O
+neurotoxicity	B-Disease
+and	O
+microglial	O
+activation	O
+are	O
+not	O
+mediated	O
+by	O
+fractalkine	O
+receptor	O
+signaling	O
+.	O
+
+Methamphetamine	B-Chemical
+(	O
+METH	B-Chemical
+)	O
+damages	O
+dopamine	B-Chemical
+(	O
+DA	B-Chemical
+)	O
+nerve	O
+endings	O
+by	O
+a	O
+process	O
+that	O
+has	O
+been	O
+linked	O
+to	O
+microglial	O
+activation	O
+but	O
+the	O
+signaling	O
+pathways	O
+that	O
+mediate	O
+this	O
+response	O
+have	O
+not	O
+yet	O
+been	O
+delineated	O
+.	O
+
+Cardona	O
+et	O
+al	O
+.	O
+
+[	O
+Nat	O
+.	O
+Neurosci	O
+.	O
+9	O
+(	O
+2006	O
+)	O
+,	O
+917	O
+]	O
+recently	O
+identified	O
+the	O
+microglial	O
+-	O
+specific	O
+fractalkine	O
+receptor	O
+(	O
+CX3CR1	O
+)	O
+as	O
+an	O
+important	O
+mediator	O
+of	O
+MPTP	B-Chemical
+-	O
+induced	O
+neurodegeneration	B-Disease
+of	O
+DA	B-Chemical
+neurons	O
+.	O
+
+Because	O
+the	O
+CNS	B-Disease
+damage	I-Disease
+caused	O
+by	O
+METH	B-Chemical
+and	O
+MPTP	B-Chemical
+is	O
+highly	O
+selective	O
+for	O
+the	O
+DA	B-Chemical
+neuronal	O
+system	O
+in	O
+mouse	O
+models	O
+of	O
+neurotoxicity	B-Disease
+,	O
+we	O
+hypothesized	O
+that	O
+the	O
+CX3CR1	O
+plays	O
+a	O
+role	O
+in	O
+METH	B-Chemical
+-	O
+induced	O
+neurotoxicity	B-Disease
+and	O
+microglial	O
+activation	O
+.	O
+
+Mice	O
+in	O
+which	O
+the	O
+CX3CR1	O
+gene	O
+has	O
+been	O
+deleted	O
+and	O
+replaced	O
+with	O
+a	O
+cDNA	O
+encoding	O
+enhanced	O
+green	O
+fluorescent	O
+protein	O
+(	O
+eGFP	O
+)	O
+were	O
+treated	O
+with	O
+METH	B-Chemical
+and	O
+examined	O
+for	O
+striatal	O
+neurotoxicity	B-Disease
+.	O
+
+METH	B-Chemical
+depleted	O
+DA	B-Chemical
+,	O
+caused	O
+microglial	O
+activation	O
+,	O
+and	O
+increased	O
+body	O
+temperature	O
+in	O
+CX3CR1	O
+knockout	O
+mice	O
+to	O
+the	O
+same	O
+extent	O
+and	O
+over	O
+the	O
+same	O
+time	O
+course	O
+seen	O
+in	O
+wild	O
+-	O
+type	O
+controls	O
+.	O
+
+The	O
+effects	O
+of	O
+METH	B-Chemical
+in	O
+CX3CR1	O
+knockout	O
+mice	O
+were	O
+not	O
+gender	O
+-	O
+dependent	O
+and	O
+did	O
+not	O
+extend	O
+beyond	O
+the	O
+striatum	O
+.	O
+
+Striatal	O
+microglia	O
+expressing	O
+eGFP	O
+constitutively	O
+show	O
+morphological	O
+changes	O
+after	O
+METH	B-Chemical
+that	O
+are	O
+characteristic	O
+of	O
+activation	O
+.	O
+
+This	O
+response	O
+was	O
+restricted	O
+to	O
+the	O
+striatum	O
+and	O
+contrasted	O
+sharply	O
+with	O
+unresponsive	O
+eGFP	O
+-	O
+microglia	O
+in	O
+surrounding	O
+brain	O
+areas	O
+that	O
+are	O
+not	O
+damaged	O
+by	O
+METH	B-Chemical
+.	O
+
+We	O
+conclude	O
+from	O
+these	O
+studies	O
+that	O
+CX3CR1	O
+signaling	O
+does	O
+not	O
+modulate	O
+METH	B-Chemical
+neurotoxicity	B-Disease
+or	O
+microglial	O
+activation	O
+.	O
+
+Furthermore	O
+,	O
+it	O
+appears	O
+that	O
+striatal	O
+-	O
+resident	O
+microglia	O
+respond	O
+to	O
+METH	B-Chemical
+with	O
+an	O
+activation	O
+cascade	O
+and	O
+then	O
+return	O
+to	O
+a	O
+surveying	O
+state	O
+without	O
+undergoing	O
+apoptosis	O
+or	O
+migration	O
+.	O
+
+Nicotine	B-Chemical
+-	O
+induced	O
+nystagmus	B-Disease
+correlates	O
+with	O
+midpontine	O
+activation	O
+.	O
+
+The	O
+pathomechanism	O
+of	O
+nicotine	B-Chemical
+-	O
+induced	O
+nystagmus	B-Disease
+(	O
+NIN	B-Disease
+)	O
+is	O
+unknown	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+delineate	O
+brain	O
+structures	O
+that	O
+are	O
+involved	O
+in	O
+NIN	B-Disease
+generation	O
+.	O
+
+Eight	O
+healthy	O
+volunteers	O
+inhaled	O
+nicotine	B-Chemical
+in	O
+darkness	O
+during	O
+a	O
+functional	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+fMRI	O
+)	O
+experiment	O
+;	O
+eye	O
+movements	O
+were	O
+registered	O
+using	O
+video	O
+-	O
+oculography	O
+.	O
+
+NIN	B-Disease
+correlated	O
+with	O
+blood	O
+oxygen	B-Chemical
+level	O
+-	O
+dependent	O
+(	O
+BOLD	O
+)	O
+activity	O
+levels	O
+in	O
+a	O
+midpontine	O
+site	O
+in	O
+the	O
+posterior	O
+basis	O
+pontis	O
+.	O
+
+NIN	B-Disease
+-	O
+induced	O
+midpontine	O
+activation	O
+may	O
+correspond	O
+to	O
+activation	O
+of	O
+the	O
+dorsomedial	O
+pontine	O
+nuclei	O
+and	O
+the	O
+nucleus	O
+reticularis	O
+tegmenti	O
+pontis	O
+,	O
+structures	O
+known	O
+to	O
+participate	O
+in	O
+the	O
+generation	O
+of	O
+multidirectional	O
+saccades	O
+and	O
+smooth	O
+pursuit	O
+eye	O
+movements	O
+.	O
+
+Acute	O
+effects	O
+of	O
+N	B-Chemical
+-	I-Chemical
+(	I-Chemical
+2	I-Chemical
+-	I-Chemical
+propylpentanoyl	I-Chemical
+)	I-Chemical
+urea	I-Chemical
+on	O
+hippocampal	O
+amino	B-Chemical
+acid	I-Chemical
+neurotransmitters	O
+in	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizure	B-Disease
+in	O
+rats	O
+.	O
+
+The	O
+present	O
+study	O
+aimed	O
+to	O
+investigate	O
+the	O
+anticonvulsant	O
+activity	O
+as	O
+well	O
+as	O
+the	O
+effects	O
+on	O
+the	O
+level	O
+of	O
+hippocampal	O
+amino	B-Chemical
+acid	I-Chemical
+neurotransmitters	O
+(	O
+glutamate	B-Chemical
+,	O
+aspartate	B-Chemical
+,	O
+glycine	B-Chemical
+and	O
+GABA	B-Chemical
+)	O
+of	O
+N	B-Chemical
+-	I-Chemical
+(	I-Chemical
+2	I-Chemical
+-	I-Chemical
+propylpentanoyl	I-Chemical
+)	I-Chemical
+urea	I-Chemical
+(	O
+VPU	B-Chemical
+)	O
+in	O
+comparison	O
+to	O
+its	O
+parent	O
+compound	O
+,	O
+valproic	B-Chemical
+acid	I-Chemical
+(	O
+VPA	B-Chemical
+)	O
+.	O
+
+VPU	B-Chemical
+was	O
+more	O
+potent	O
+than	O
+VPA	B-Chemical
+,	O
+exhibiting	O
+the	O
+median	O
+effective	O
+dose	O
+(	O
+ED	O
+(	O
+50	O
+)	O
+)	O
+of	O
+49	O
+mg	O
+/	O
+kg	O
+in	O
+protecting	O
+rats	O
+against	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizure	B-Disease
+whereas	O
+the	O
+corresponding	O
+value	O
+for	O
+VPA	B-Chemical
+was	O
+322	O
+mg	O
+/	O
+kg	O
+.	O
+
+In	O
+vivo	O
+microdialysis	O
+demonstrated	O
+that	O
+an	O
+intraperitoneal	O
+administration	O
+of	O
+pilocarpine	B-Chemical
+induced	O
+a	O
+pronounced	O
+increment	O
+of	O
+hippocampal	O
+glutamate	B-Chemical
+and	O
+aspartate	B-Chemical
+whereas	O
+no	O
+significant	O
+change	O
+was	O
+observed	O
+on	O
+the	O
+level	O
+of	O
+glycine	B-Chemical
+and	O
+GABA	B-Chemical
+.	O
+
+Pretreatment	O
+with	O
+either	O
+VPU	B-Chemical
+(	O
+50	O
+and	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+or	O
+VPA	B-Chemical
+(	O
+300	O
+and	O
+600	O
+mg	O
+/	O
+kg	O
+)	O
+completely	O
+abolished	O
+pilocarpine	B-Chemical
+-	O
+evoked	O
+increases	O
+in	O
+extracellular	O
+glutamate	B-Chemical
+and	O
+aspartate	B-Chemical
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+statistically	O
+significant	O
+reduction	O
+was	O
+also	O
+observed	O
+on	O
+the	O
+level	O
+of	O
+GABA	B-Chemical
+and	O
+glycine	B-Chemical
+but	O
+less	O
+than	O
+a	O
+drastic	O
+reduction	O
+of	O
+glutamate	B-Chemical
+and	O
+aspartate	B-Chemical
+level	O
+.	O
+
+Based	O
+on	O
+the	O
+finding	O
+that	O
+VPU	B-Chemical
+and	O
+VPA	B-Chemical
+could	O
+protect	O
+the	O
+animals	O
+against	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizure	B-Disease
+it	O
+is	O
+suggested	O
+that	O
+the	O
+reduction	O
+of	O
+inhibitory	O
+amino	B-Chemical
+acid	I-Chemical
+neurotransmitters	O
+was	O
+comparatively	O
+minor	O
+and	O
+offset	O
+by	O
+a	O
+pronounced	O
+reduction	O
+of	O
+glutamate	B-Chemical
+and	O
+aspartate	B-Chemical
+.	O
+
+Therefore	O
+,	O
+like	O
+VPA	B-Chemical
+,	O
+the	O
+finding	O
+that	O
+VPU	B-Chemical
+could	O
+drastically	O
+reduce	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+increases	O
+in	O
+glutamate	B-Chemical
+and	O
+aspartate	B-Chemical
+should	O
+account	O
+,	O
+at	O
+least	O
+partly	O
+,	O
+for	O
+its	O
+anticonvulsant	O
+activity	O
+observed	O
+in	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+seizure	B-Disease
+in	O
+experimental	O
+animals	O
+.	O
+
+Some	O
+other	O
+mechanism	O
+than	O
+those	O
+being	O
+reported	O
+herein	O
+should	O
+be	O
+further	O
+investigated	O
+.	O
+
+Protective	O
+effect	O
+of	O
+verapamil	B-Chemical
+on	O
+gastric	B-Disease
+hemorrhagic	I-Disease
+ulcers	B-Disease
+in	O
+severe	O
+atherosclerotic	B-Disease
+rats	O
+.	O
+
+Studies	O
+concerning	O
+with	O
+pathogenesis	O
+of	O
+gastric	B-Disease
+hemorrhage	I-Disease
+and	O
+mucosal	O
+ulceration	O
+produced	O
+in	O
+atherosclerotic	B-Disease
+rats	O
+are	O
+lacking	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+is	O
+to	O
+examine	O
+the	O
+role	O
+of	O
+gastric	O
+acid	O
+back	O
+-	O
+diffusion	O
+,	O
+mast	O
+cell	O
+histamine	B-Chemical
+release	O
+,	O
+lipid	O
+peroxide	O
+(	O
+LPO	O
+)	O
+generation	O
+and	O
+mucosal	O
+microvascular	O
+permeability	O
+in	O
+modulating	O
+gastric	B-Disease
+hemorrhage	I-Disease
+and	O
+ulcer	B-Disease
+in	O
+rats	O
+with	O
+atherosclerosis	B-Disease
+induced	O
+by	O
+coadministration	O
+of	O
+vitamin	B-Chemical
+D2	I-Chemical
+and	O
+cholesterol	B-Chemical
+.	O
+
+Additionally	O
+,	O
+the	O
+protective	O
+effect	O
+of	O
+verapamil	B-Chemical
+on	O
+this	O
+ulcer	B-Disease
+model	O
+was	O
+evaluated	O
+.	O
+
+Male	O
+Wistar	O
+rats	O
+were	O
+challenged	O
+intragastrically	O
+once	O
+daily	O
+for	O
+9	O
+days	O
+with	O
+1	O
+.	O
+0	O
+ml	O
+/	O
+kg	O
+of	O
+corn	O
+oil	O
+containing	O
+vitamin	B-Chemical
+D2	I-Chemical
+and	O
+cholesterol	B-Chemical
+to	O
+induce	O
+atherosclerosis	B-Disease
+.	O
+
+Control	O
+rats	O
+received	O
+corn	O
+oil	O
+only	O
+.	O
+
+After	O
+gastric	O
+surgery	O
+,	O
+rat	O
+stomachs	O
+were	O
+irrigated	O
+for	O
+3	O
+h	O
+with	O
+either	O
+simulated	O
+gastric	O
+juice	O
+or	O
+normal	O
+saline	O
+.	O
+
+Gastric	O
+acid	O
+back	O
+-	O
+diffusion	O
+,	O
+mucosal	O
+LPO	O
+generation	O
+,	O
+histamine	B-Chemical
+concentration	O
+,	O
+microvascular	O
+permeability	O
+,	O
+luminal	B-Chemical
+hemoglobin	O
+content	O
+and	O
+ulcer	B-Disease
+areas	O
+were	O
+determined	O
+.	O
+
+Elevated	O
+atherosclerotic	B-Disease
+parameters	O
+,	O
+such	O
+as	O
+serum	O
+calcium	B-Chemical
+,	O
+total	O
+cholesterol	B-Chemical
+and	O
+low	O
+-	O
+density	O
+lipoprotein	O
+concentration	O
+were	O
+obtained	O
+in	O
+atherosclerotic	B-Disease
+rats	O
+.	O
+
+Severe	O
+gastric	O
+ulcers	B-Disease
+accompanied	O
+with	O
+increased	O
+ulcerogenic	O
+factors	O
+,	O
+including	O
+gastric	O
+acid	O
+back	O
+-	O
+diffusion	O
+,	O
+histamine	B-Chemical
+release	O
+,	O
+LPO	O
+generation	O
+and	O
+luminal	B-Chemical
+hemoglobin	O
+content	O
+were	O
+also	O
+observed	O
+in	O
+these	O
+rats	O
+.	O
+
+Moreover	O
+,	O
+a	O
+positive	O
+correlation	O
+of	O
+histamine	B-Chemical
+to	O
+gastric	B-Disease
+hemorrhage	I-Disease
+and	O
+to	O
+ulcer	B-Disease
+was	O
+found	O
+in	O
+those	O
+atherosclerotic	B-Disease
+rats	O
+.	O
+
+This	O
+hemorrhagic	B-Disease
+ulcer	B-Disease
+and	O
+various	O
+ulcerogenic	O
+parameters	O
+were	O
+dose	O
+-	O
+dependently	O
+ameliorated	O
+by	O
+daily	O
+intragastric	O
+verapamil	B-Chemical
+.	O
+
+Atherosclerosis	B-Disease
+could	O
+produce	O
+gastric	B-Disease
+hemorrhagic	I-Disease
+ulcer	B-Disease
+via	O
+aggravation	O
+of	O
+gastric	O
+acid	O
+back	O
+-	O
+diffusion	O
+,	O
+LPO	O
+generation	O
+,	O
+histamine	B-Chemical
+release	O
+and	O
+microvascular	O
+permeability	O
+that	O
+could	O
+be	O
+ameliorated	O
+by	O
+verapamil	B-Chemical
+in	O
+rats	O
+.	O
+
+Lamivudine	B-Chemical
+for	O
+the	O
+prevention	O
+of	O
+hepatitis	B-Disease
+B	I-Disease
+virus	O
+reactivation	O
+in	O
+hepatitis	B-Chemical
+-	I-Chemical
+B	I-Chemical
+surface	I-Chemical
+antigen	I-Chemical
+(	O
+HBSAG	B-Chemical
+)	O
+seropositive	O
+cancer	B-Disease
+patients	O
+undergoing	O
+cytotoxic	O
+chemotherapy	O
+.	O
+
+Hepatitis	B-Disease
+B	I-Disease
+virus	O
+(	O
+HBV	O
+)	O
+is	O
+one	O
+of	O
+the	O
+major	O
+causes	O
+of	O
+chronic	O
+liver	B-Disease
+disease	I-Disease
+worldwide	O
+.	O
+
+Cancer	B-Disease
+patients	O
+who	O
+are	O
+chronic	O
+carriers	O
+of	O
+HBV	O
+have	O
+a	O
+higher	O
+hepatic	B-Disease
+complication	I-Disease
+rate	O
+while	O
+receiving	O
+cytotoxic	O
+chemotherapy	O
+(	O
+CT	O
+)	O
+and	O
+this	O
+has	O
+mainly	O
+been	O
+attributed	O
+to	O
+HBV	O
+reactivation	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+cancer	B-Disease
+patients	O
+who	O
+have	O
+solid	O
+and	O
+hematological	B-Disease
+malignancies	I-Disease
+with	O
+chronic	O
+HBV	B-Disease
+infection	I-Disease
+received	O
+the	O
+antiviral	O
+agent	O
+lamivudine	B-Chemical
+prior	O
+and	O
+during	O
+CT	O
+compared	O
+with	O
+historical	O
+control	O
+group	O
+who	O
+did	O
+not	O
+receive	O
+lamivudine	B-Chemical
+.	O
+
+The	O
+objectives	O
+were	O
+to	O
+assess	O
+the	O
+efficacy	O
+of	O
+lamivudine	B-Chemical
+in	O
+reducing	O
+the	O
+incidence	O
+of	O
+HBV	O
+reactivation	O
+,	O
+and	O
+diminishing	O
+morbidity	O
+and	O
+mortality	O
+during	O
+CT	O
+.	O
+
+Two	O
+groups	O
+were	O
+compared	O
+in	O
+this	O
+study	O
+.	O
+
+The	O
+prophylactic	O
+lamivudin	B-Chemical
+group	O
+consisted	O
+of	O
+37	O
+patients	O
+who	O
+received	O
+prophylactic	O
+lamivudine	B-Chemical
+treatment	O
+.	O
+
+The	O
+historical	O
+controls	O
+consisted	O
+of	O
+50	O
+consecutive	O
+patients	O
+who	O
+underwent	O
+CT	O
+without	O
+prophylactic	O
+lamivudine	B-Chemical
+.	O
+
+They	O
+were	O
+followed	O
+up	O
+during	O
+and	O
+for	O
+8	O
+weeks	O
+after	O
+CT	O
+.	O
+
+The	O
+outcomes	O
+were	O
+compared	O
+for	O
+both	O
+groups	O
+.	O
+
+Of	O
+our	O
+control	O
+group	O
+(	O
+n	O
+=	O
+50	O
+)	O
+,	O
+21	O
+patients	O
+(	O
+42	O
+%	O
+)	O
+were	O
+established	O
+hepatitis	B-Disease
+.	O
+
+Twelve	O
+(	O
+24	O
+%	O
+)	O
+of	O
+them	O
+were	O
+evaluated	O
+as	O
+severe	O
+hepatitis	B-Disease
+.	O
+
+In	O
+the	O
+prophylactic	O
+lamivudine	B-Chemical
+group	O
+severe	O
+hepatitis	B-Disease
+were	O
+observed	O
+only	O
+in	O
+1	O
+patient	O
+(	O
+2	O
+.	O
+7	O
+%	O
+)	O
+of	O
+37	O
+patients	O
+(	O
+p	O
+<	O
+0	O
+.	O
+006	O
+)	O
+.	O
+
+Comparison	O
+of	O
+the	O
+mean	O
+ALT	O
+values	O
+revealed	O
+significantly	O
+higher	O
+mean	O
+alanine	B-Chemical
+aminotransferase	O
+(	O
+ALT	O
+)	O
+values	O
+in	O
+the	O
+control	O
+group	O
+than	O
+the	O
+prophylactic	O
+lamivudine	B-Chemical
+group	O
+;	O
+154	O
+:	O
+64	O
+(	O
+p	O
+<	O
+0	O
+.	O
+32	O
+)	O
+.	O
+
+Our	O
+study	O
+suggests	O
+that	O
+prophylactic	O
+lamivudine	B-Chemical
+significantly	O
+decreases	O
+the	O
+incidence	O
+of	O
+HBV	O
+reactivation	O
+and	O
+overall	O
+morbidity	O
+in	O
+cancer	B-Disease
+patients	O
+during	O
+and	O
+after	O
+immunosuppressive	O
+therapy	O
+.	O
+
+Further	O
+studies	O
+are	O
+needed	O
+to	O
+determine	O
+the	O
+most	O
+appropriate	O
+nucleoside	B-Chemical
+or	O
+nucleotide	B-Chemical
+analogue	O
+for	O
+antiviral	O
+prophylaxis	O
+during	O
+CT	O
+and	O
+the	O
+optimal	O
+duration	O
+of	O
+administration	O
+after	O
+completion	O
+of	O
+CT	O
+.	O
+
+Recovery	O
+of	O
+tacrolimus	B-Chemical
+-	O
+associated	O
+brachial	B-Disease
+neuritis	I-Disease
+after	O
+conversion	O
+to	O
+everolimus	B-Chemical
+in	O
+a	O
+pediatric	O
+renal	O
+transplant	O
+recipient	O
+-	O
+-	O
+case	O
+report	O
+and	O
+review	O
+of	O
+the	O
+literature	O
+.	O
+
+TAC	B-Chemical
+has	O
+been	O
+shown	O
+to	O
+be	O
+a	O
+potent	O
+immunosuppressive	O
+agent	O
+for	O
+solid	O
+organ	O
+transplantation	O
+in	O
+pediatrics	O
+.	O
+
+Neurotoxicity	B-Disease
+is	O
+a	O
+potentially	O
+serious	O
+toxic	O
+effect	O
+.	O
+
+It	O
+is	O
+characterized	O
+by	O
+encephalopathy	B-Disease
+,	O
+headaches	B-Disease
+,	O
+seizures	B-Disease
+,	O
+or	O
+neurological	B-Disease
+deficits	I-Disease
+.	O
+
+Here	O
+,	O
+we	O
+describe	O
+an	O
+eight	O
+-	O
+and	O
+-	O
+a	O
+-	O
+half	O
+-	O
+yr	O
+-	O
+old	O
+male	O
+renal	O
+transplant	O
+recipient	O
+with	O
+right	O
+BN	O
+.	O
+
+MRI	O
+demonstrated	O
+hyperintense	O
+T2	O
+signals	O
+in	O
+the	O
+cervical	O
+cord	O
+and	O
+right	O
+brachial	O
+plexus	O
+roots	O
+indicative	O
+of	O
+both	O
+myelitis	B-Disease
+and	O
+right	O
+brachial	B-Disease
+plexitis	I-Disease
+.	O
+
+Symptoms	O
+persisted	O
+for	O
+three	O
+months	O
+despite	O
+TAC	B-Chemical
+dose	O
+reduction	O
+,	O
+administration	O
+of	O
+IVIG	O
+and	O
+four	O
+doses	O
+of	O
+methylprednisolone	B-Chemical
+pulse	O
+therapy	O
+.	O
+
+Improvement	O
+and	O
+eventually	O
+full	O
+recovery	O
+only	O
+occurred	O
+after	O
+TAC	B-Chemical
+was	O
+completely	O
+discontinued	O
+and	O
+successfully	O
+replaced	O
+by	O
+everolimus	B-Chemical
+.	O
+
+Omitting	O
+fentanyl	B-Chemical
+reduces	O
+nausea	B-Disease
+and	O
+vomiting	B-Disease
+,	O
+without	O
+increasing	O
+pain	B-Disease
+,	O
+after	O
+sevoflurane	B-Chemical
+for	O
+day	O
+surgery	O
+.	O
+
+BACKGROUND	O
+AND	O
+OBJECTIVE	O
+:	O
+Despite	O
+advantages	O
+of	O
+induction	O
+and	O
+maintenance	O
+of	O
+anaesthesia	O
+with	O
+sevoflurane	B-Chemical
+,	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+occurs	O
+frequently	O
+.	O
+
+Fentanyl	B-Chemical
+is	O
+a	O
+commonly	O
+used	O
+supplement	O
+that	O
+may	O
+contribute	O
+to	O
+this	O
+,	O
+although	O
+it	O
+may	O
+also	O
+improve	O
+analgesia	O
+.	O
+
+METHODS	O
+:	O
+This	O
+double	O
+-	O
+blind	O
+study	O
+examined	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+and	O
+pain	B-Disease
+in	O
+the	O
+first	O
+24	O
+h	O
+after	O
+sevoflurane	B-Chemical
+anaesthesia	O
+in	O
+216	O
+adult	O
+day	O
+surgery	O
+patients	O
+.	O
+
+Patients	O
+were	O
+randomly	O
+allocated	O
+to	O
+either	O
+receive	O
+or	O
+not	O
+receive	O
+1	O
+1	O
+fentanyl	B-Chemical
+,	O
+while	O
+a	O
+third	O
+group	O
+received	O
+dexamethasone	B-Chemical
+in	O
+addition	O
+to	O
+fentanyl	B-Chemical
+.	O
+
+RESULTS	O
+:	O
+Omission	O
+of	O
+fentanyl	B-Chemical
+did	O
+not	O
+reduce	O
+the	O
+overall	O
+incidence	O
+of	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+,	O
+but	O
+did	O
+reduce	O
+the	O
+incidence	O
+of	O
+vomiting	B-Disease
+and	O
+/	O
+or	O
+moderate	O
+to	O
+severe	O
+nausea	B-Disease
+prior	O
+to	O
+discharge	O
+from	O
+20	O
+%	O
+and	O
+17	O
+%	O
+with	O
+fentanyl	B-Chemical
+and	O
+fentanyl	B-Chemical
+-	O
+dexamethasone	B-Chemical
+,	O
+respectively	O
+,	O
+to	O
+5	O
+%	O
+(	O
+P	O
+=	O
+0	O
+.	O
+013	O
+)	O
+.	O
+
+Antiemetic	O
+requirements	O
+were	O
+reduced	O
+from	O
+24	O
+%	O
+and	O
+31	O
+%	O
+to	O
+7	O
+%	O
+(	O
+P	O
+=	O
+0	O
+.	O
+0012	O
+)	O
+.	O
+
+Dexamethasone	B-Chemical
+had	O
+no	O
+significant	O
+effect	O
+on	O
+the	O
+incidence	O
+or	O
+severity	O
+of	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+.	O
+
+Combining	O
+the	O
+two	O
+fentanyl	B-Chemical
+groups	O
+revealed	O
+further	O
+significant	O
+benefits	O
+from	O
+the	O
+avoidance	O
+of	O
+opioids	O
+,	O
+reducing	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+and	O
+nausea	B-Disease
+prior	O
+to	O
+discharge	O
+from	O
+35	O
+%	O
+and	O
+33	O
+%	O
+to	O
+22	O
+%	O
+and	O
+19	O
+%	O
+(	O
+P	O
+=	O
+0	O
+.	O
+049	O
+and	O
+P	O
+=	O
+0	O
+.	O
+035	O
+)	O
+,	O
+respectively	O
+,	O
+while	O
+nausea	B-Disease
+in	O
+the	O
+first	O
+24	O
+h	O
+was	O
+decreased	O
+from	O
+42	O
+%	O
+to	O
+27	O
+%	O
+(	O
+P	O
+=	O
+0	O
+.	O
+034	O
+)	O
+.	O
+
+Pain	B-Disease
+severity	O
+and	O
+analgesic	O
+requirements	O
+were	O
+unaffected	O
+by	O
+the	O
+omission	O
+of	O
+fentanyl	B-Chemical
+.	O
+
+Fentanyl	B-Chemical
+did	O
+reduce	O
+minor	O
+intraoperative	O
+movement	O
+but	O
+had	O
+no	O
+sevoflurane	B-Chemical
+-	O
+sparing	O
+effect	O
+and	O
+increased	O
+respiratory	B-Disease
+depression	I-Disease
+,	O
+hypotension	B-Disease
+and	O
+bradycardia	B-Disease
+.	O
+
+CONCLUSION	O
+:	O
+As	O
+fentanyl	B-Chemical
+exacerbated	O
+postoperative	B-Disease
+nausea	I-Disease
+and	I-Disease
+vomiting	I-Disease
+without	O
+an	O
+improvement	O
+in	O
+postoperative	B-Disease
+pain	I-Disease
+and	O
+also	O
+had	O
+adverse	O
+cardiorespiratory	O
+effects	O
+,	O
+it	O
+appears	O
+to	O
+be	O
+an	O
+unnecessary	O
+and	O
+possibly	O
+detrimental	O
+supplement	O
+to	O
+sevoflurane	B-Chemical
+in	O
+day	O
+surgery	O
+.	O
+
+Valvular	B-Disease
+heart	I-Disease
+disease	I-Disease
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+treated	O
+with	O
+pergolide	B-Chemical
+.	O
+
+Course	O
+following	O
+treatment	O
+modifications	O
+.	O
+
+Valvular	B-Disease
+heart	I-Disease
+abnormalities	I-Disease
+have	O
+been	O
+reported	O
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+treated	O
+with	O
+pergolide	B-Chemical
+.	O
+
+However	O
+,	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+these	O
+abnormalities	O
+vary	O
+from	O
+study	O
+to	O
+study	O
+and	O
+their	O
+course	O
+after	O
+drug	O
+withdrawal	O
+has	O
+not	O
+been	O
+systematically	O
+assessed	O
+.	O
+
+OBJECTIVES	O
+:	O
+To	O
+estimate	O
+the	O
+frequency	O
+and	O
+severity	O
+of	O
+valvular	B-Disease
+heart	I-Disease
+abnormality	I-Disease
+and	O
+its	O
+possible	O
+reversibility	O
+after	O
+drug	O
+withdrawal	O
+in	O
+a	O
+case	O
+-	O
+control	O
+study	O
+.	O
+
+METHODS	O
+:	O
+All	O
+PD	B-Disease
+patients	O
+in	O
+the	O
+Amiens	O
+area	O
+treated	O
+with	O
+pergolide	B-Chemical
+were	O
+invited	O
+to	O
+attend	O
+a	O
+cardiologic	O
+assessment	O
+including	O
+transthoracic	O
+echocardiography	O
+.	O
+
+Thirty	O
+PD	B-Disease
+patients	O
+participated	O
+in	O
+the	O
+study	O
+.	O
+
+A	O
+second	O
+echocardiography	O
+was	O
+performed	O
+(	O
+median	O
+interval	O
+:	O
+13	O
+months	O
+)	O
+after	O
+pergolide	B-Chemical
+withdrawal	O
+(	O
+n	O
+=	O
+10	O
+patients	O
+)	O
+.	O
+
+Controls	O
+were	O
+age	O
+-	O
+and	O
+sex	O
+-	O
+matched	O
+non	O
+-	O
+PD	B-Disease
+patients	O
+referred	O
+to	O
+the	O
+cardiology	O
+department	O
+.	O
+
+RESULTS	O
+:	O
+Compared	O
+to	O
+controls	O
+,	O
+aortic	B-Disease
+regurgitation	I-Disease
+(	O
+OR	O
+:	O
+3	O
+.	O
+1	O
+;	O
+95	O
+%	O
+IC	O
+:	O
+1	O
+.	O
+1	O
+-	O
+8	O
+.	O
+8	O
+)	O
+and	O
+mitral	B-Disease
+regurgitation	I-Disease
+(	O
+OR	O
+:	O
+10	O
+.	O
+7	O
+;	O
+95	O
+%	O
+IC	O
+:	O
+2	O
+.	O
+1	O
+-	O
+53	O
+)	O
+were	O
+more	O
+frequent	O
+in	O
+PD	B-Disease
+patients	O
+(	O
+tricuspid	O
+:	O
+NS	O
+)	O
+.	O
+
+The	O
+number	O
+of	O
+affected	O
+valves	O
+(	O
+n	O
+=	O
+2	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+)	O
+and	O
+the	O
+sum	O
+of	O
+regurgitation	O
+grades	O
+(	O
+n	O
+=	O
+2	O
+.	O
+8	O
++	O
+/	O
+-	O
+1	O
+.	O
+09	O
+)	O
+were	O
+higher	O
+(	O
+p	O
+=	O
+0	O
+.	O
+008	O
+and	O
+p	O
+=	O
+0	O
+.	O
+006	O
+,	O
+respectively	O
+)	O
+in	O
+the	O
+pergolide	B-Chemical
+group	O
+.	O
+
+Severity	O
+of	O
+regurgitation	O
+was	O
+not	O
+correlated	O
+with	O
+pergolide	B-Chemical
+cumulative	O
+dose	O
+.	O
+
+A	O
+restrictive	O
+pattern	O
+of	O
+valvular	B-Disease
+regurgitation	I-Disease
+,	O
+suggestive	O
+of	O
+the	O
+role	O
+of	O
+pergolide	B-Chemical
+,	O
+was	O
+observed	O
+in	O
+12	O
+/	O
+30	O
+(	O
+40	O
+%	O
+)	O
+patients	O
+including	O
+two	O
+with	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+Pergolide	B-Chemical
+was	O
+discontinued	O
+in	O
+10	O
+patients	O
+with	O
+valvular	B-Disease
+heart	I-Disease
+disease	I-Disease
+,	O
+resulting	O
+in	O
+a	O
+lower	O
+regurgitation	O
+grade	O
+(	O
+p	O
+=	O
+0	O
+.	O
+01	O
+)	O
+at	O
+the	O
+second	O
+transthoracic	O
+echocardiography	O
+and	O
+the	O
+two	O
+patients	O
+with	O
+heart	B-Disease
+failure	I-Disease
+returned	O
+to	O
+nearly	O
+normal	O
+clinical	O
+examination	O
+.	O
+
+This	O
+study	O
+supports	O
+the	O
+high	O
+frequency	O
+of	O
+restrictive	O
+valve	B-Disease
+regurgitation	I-Disease
+in	O
+PD	B-Disease
+patients	O
+treated	O
+with	O
+pergolide	B-Chemical
+and	O
+reveals	O
+that	O
+a	O
+significant	O
+improvement	O
+is	O
+usual	O
+when	O
+the	O
+treatment	O
+is	O
+converted	O
+to	O
+non	O
+-	O
+ergot	O
+dopamine	B-Chemical
+agonists	O
+.	O
+
+Adriamycin	B-Chemical
+-	O
+induced	O
+autophagic	O
+cardiomyocyte	O
+death	B-Disease
+plays	O
+a	O
+pathogenic	O
+role	O
+in	O
+a	O
+rat	O
+model	O
+of	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+mechanisms	O
+underlying	O
+heart	B-Disease
+failure	I-Disease
+induced	O
+by	O
+adriamycin	B-Chemical
+are	O
+very	O
+complicated	O
+and	O
+still	O
+unclear	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+whether	O
+autophagy	O
+was	O
+involved	O
+in	O
+the	O
+progression	O
+of	O
+heart	B-Disease
+failure	I-Disease
+induced	O
+by	O
+adriamycin	B-Chemical
+,	O
+so	O
+that	O
+we	O
+can	O
+develop	O
+a	O
+novel	O
+treatment	O
+strategy	O
+for	O
+heart	B-Disease
+failure	I-Disease
+.	O
+
+METHODS	O
+:	O
+3	B-Chemical
+-	I-Chemical
+methyladenine	I-Chemical
+(	O
+3MA	B-Chemical
+)	O
+,	O
+a	O
+specific	O
+inhibitor	O
+on	O
+autophagy	O
+was	O
+used	O
+in	O
+a	O
+heart	B-Disease
+failure	I-Disease
+model	O
+of	O
+rats	O
+induced	O
+by	O
+adriamycin	B-Chemical
+.	O
+
+Neonatal	O
+cardiomyocytes	O
+were	O
+isolated	O
+from	O
+Sprague	O
+-	O
+Dawley	O
+rat	O
+hearts	O
+and	O
+randomly	O
+divided	O
+into	O
+controls	O
+,	O
+an	O
+adriamycin	B-Chemical
+-	O
+treated	O
+group	O
+,	O
+and	O
+a	O
+3MA	B-Chemical
+plus	O
+adriamycin	B-Chemical
+-	O
+treated	O
+group	O
+.	O
+
+We	O
+then	O
+examined	O
+the	O
+morphology	O
+,	O
+expression	O
+of	O
+beclin	O
+1	O
+gene	O
+,	O
+mitochondrial	O
+permeability	O
+transition	O
+(	O
+MPT	O
+)	O
+,	O
+and	O
+Na	O
++	O
+-	O
+K	B-Chemical
++	O
+ATPase	O
+activity	O
+in	O
+vivo	O
+.	O
+
+We	O
+also	O
+assessed	O
+cell	O
+viability	O
+,	O
+mitochondrial	O
+membrane	O
+potential	O
+changes	O
+and	O
+counted	O
+autophagic	O
+vacuoles	O
+in	O
+cultured	O
+cardiomyocytes	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+analyzed	O
+the	O
+expression	O
+of	O
+autophagy	O
+associated	O
+gene	O
+,	O
+beclin	O
+1	O
+using	O
+RT	O
+-	O
+PCR	O
+and	O
+Western	O
+blotting	O
+in	O
+an	O
+animal	O
+model	O
+.	O
+
+RESULTS	O
+:	O
+3MA	B-Chemical
+significantly	O
+improved	O
+cardiac	O
+function	O
+and	O
+reduced	O
+mitochondrial	O
+injury	O
+.	O
+
+Furthermore	O
+,	O
+adriamycin	B-Chemical
+induced	O
+the	O
+formation	O
+of	O
+autophagic	O
+vacuoles	O
+,	O
+and	O
+3MA	B-Chemical
+strongly	O
+downregulated	O
+the	O
+expression	O
+of	O
+beclin	O
+1	O
+in	O
+adriamycin	B-Chemical
+-	O
+induced	O
+failing	O
+heart	O
+and	O
+inhibited	O
+the	O
+formation	O
+of	O
+autophagic	O
+vacuoles	O
+.	O
+
+CONCLUSION	O
+:	O
+Autophagic	O
+cardiomyocyte	O
+death	B-Disease
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+pathogenesis	O
+of	O
+heart	B-Disease
+failure	I-Disease
+in	O
+rats	O
+induced	O
+by	O
+adriamycin	B-Chemical
+.	O
+
+Mitochondrial	O
+injury	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+progression	O
+of	O
+heart	B-Disease
+failure	I-Disease
+caused	O
+by	O
+adriamycin	B-Chemical
+via	O
+the	O
+autophagy	O
+pathway	O
+.	O
+
+mToR	O
+inhibitors	O
+-	O
+induced	O
+proteinuria	B-Disease
+:	O
+mechanisms	O
+,	O
+significance	O
+,	O
+and	O
+management	O
+.	O
+
+Massive	O
+urinary	O
+protein	O
+excretion	O
+has	O
+been	O
+observed	O
+after	O
+conversion	O
+from	O
+calcineurin	O
+inhibitors	O
+to	O
+mammalian	O
+target	O
+of	O
+rapamycin	B-Chemical
+(	O
+mToR	O
+)	O
+inhibitors	O
+,	O
+especially	O
+sirolimus	B-Chemical
+,	O
+in	O
+renal	O
+transplant	O
+recipients	O
+with	O
+chronic	B-Disease
+allograft	I-Disease
+nephropathy	I-Disease
+.	O
+
+Because	O
+proteinuria	B-Disease
+is	O
+a	O
+major	O
+predictive	O
+factor	O
+of	O
+poor	O
+transplantation	O
+outcome	O
+,	O
+many	O
+studies	O
+focused	O
+on	O
+this	O
+adverse	O
+event	O
+during	O
+the	O
+past	O
+years	O
+.	O
+
+Whether	O
+proteinuria	B-Disease
+was	O
+due	O
+to	O
+sirolimus	B-Chemical
+or	O
+only	O
+a	O
+consequence	O
+of	O
+calcineurin	O
+inhibitors	O
+withdrawal	O
+remained	O
+unsolved	O
+until	O
+high	O
+range	O
+proteinuria	B-Disease
+has	O
+been	O
+observed	O
+during	O
+sirolimus	B-Chemical
+therapy	O
+in	O
+islet	O
+transplantation	O
+and	O
+in	O
+patients	O
+who	O
+received	O
+sirolimus	B-Chemical
+de	O
+novo	O
+.	O
+
+Podocyte	O
+injury	O
+and	O
+focal	O
+segmental	O
+glomerulosclerosis	B-Disease
+have	O
+been	O
+related	O
+to	O
+mToR	O
+inhibition	O
+in	O
+some	O
+patients	O
+,	O
+but	O
+the	O
+pathways	O
+underlying	O
+these	O
+lesions	O
+remain	O
+hypothetic	O
+.	O
+
+We	O
+discuss	O
+herein	O
+the	O
+possible	O
+mechanisms	O
+and	O
+the	O
+significance	O
+of	O
+mToR	O
+blockade	O
+-	O
+induced	O
+proteinuria	B-Disease
+.	O
+
+Neuropsychiatric	O
+side	O
+effects	O
+after	O
+the	O
+use	O
+of	O
+mefloquine	B-Chemical
+.	O
+
+This	O
+study	O
+describes	O
+neuropsychiatric	O
+side	O
+effects	O
+in	O
+patients	O
+after	O
+treatment	O
+with	O
+mefloquine	B-Chemical
+.	O
+
+Reactions	O
+consisted	O
+mainly	O
+of	O
+seizures	B-Disease
+,	O
+acute	O
+psychoses	B-Disease
+,	O
+anxiety	B-Disease
+neurosis	I-Disease
+,	O
+and	O
+major	O
+disturbances	B-Disease
+of	I-Disease
+sleep	I-Disease
+-	I-Disease
+wake	I-Disease
+rhythm	I-Disease
+.	O
+
+Side	O
+effects	O
+occurred	O
+after	O
+both	O
+therapeutic	O
+and	O
+prophylactic	O
+intake	O
+and	O
+were	O
+graded	O
+from	O
+moderate	O
+to	O
+severe	O
+.	O
+
+In	O
+a	O
+risk	O
+analysis	O
+of	O
+neuropsychiatric	O
+side	O
+effects	O
+in	O
+Germany	O
+,	O
+it	O
+is	O
+estimated	O
+that	O
+one	O
+of	O
+8	O
+,	O
+000	O
+mefloquine	B-Chemical
+users	O
+suffers	O
+from	O
+such	O
+reactions	O
+.	O
+
+The	O
+incidence	O
+calculation	O
+revealed	O
+that	O
+one	O
+of	O
+215	O
+therapeutic	O
+users	O
+had	O
+reactions	O
+,	O
+compared	O
+with	O
+one	O
+of	O
+13	O
+,	O
+000	O
+in	O
+the	O
+prophylaxis	O
+group	O
+,	O
+making	O
+the	O
+risk	O
+of	O
+neuropsychiatric	O
+reactions	O
+after	O
+mefloquine	B-Chemical
+treatment	O
+60	O
+times	O
+higher	O
+than	O
+after	O
+prophylaxis	O
+.	O
+
+Therefore	O
+,	O
+certain	O
+limitations	O
+for	O
+malaria	B-Disease
+prophylaxis	O
+and	O
+treatment	O
+with	O
+mefloquine	B-Chemical
+are	O
+recommended	O
+.	O
+
+Prenatal	O
+protein	O
+deprivation	O
+alters	O
+dopamine	B-Chemical
+-	O
+mediated	O
+behaviors	O
+and	O
+dopaminergic	O
+and	O
+glutamatergic	O
+receptor	O
+binding	O
+.	O
+
+Epidemiological	O
+evidence	O
+indicates	O
+that	O
+prenatal	O
+nutritional	O
+deprivation	O
+may	O
+increase	O
+the	O
+risk	O
+of	O
+schizophrenia	B-Disease
+.	O
+
+The	O
+goal	O
+of	O
+these	O
+studies	O
+was	O
+to	O
+use	O
+an	O
+animal	O
+model	O
+to	O
+examine	O
+the	O
+effects	O
+of	O
+prenatal	O
+protein	O
+deprivation	O
+on	O
+behaviors	O
+and	O
+receptor	O
+binding	O
+with	O
+relevance	O
+to	O
+schizophrenia	B-Disease
+.	O
+
+We	O
+report	O
+that	O
+prenatally	O
+protein	O
+deprived	O
+(	O
+PD	O
+)	O
+female	O
+rats	O
+showed	O
+an	O
+increased	O
+stereotypic	O
+response	O
+to	O
+apomorphine	B-Chemical
+and	O
+an	O
+increased	O
+locomotor	O
+response	O
+to	O
+amphetamine	B-Chemical
+in	O
+adulthood	O
+.	O
+
+These	O
+differences	O
+were	O
+not	O
+observed	O
+during	O
+puberty	O
+.	O
+
+No	O
+changes	O
+in	O
+haloperidol	B-Chemical
+-	O
+induced	O
+catalepsy	B-Disease
+or	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+-	O
+induced	O
+locomotion	O
+were	O
+seen	O
+following	O
+PD	O
+.	O
+
+In	O
+addition	O
+,	O
+PD	O
+female	O
+rats	O
+showed	O
+increased	O
+(	O
+3	O
+)	O
+H	B-Chemical
+-	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+binding	O
+in	O
+the	O
+striatum	O
+and	O
+hippocampus	O
+,	O
+but	O
+not	O
+in	O
+the	O
+cortex	O
+.	O
+
+PD	O
+female	O
+rats	O
+also	O
+showed	O
+increased	O
+(	O
+3	O
+)	O
+H	B-Chemical
+-	O
+haloperidol	B-Chemical
+binding	O
+and	O
+decreased	O
+dopamine	B-Chemical
+transporter	O
+binding	O
+in	O
+striatum	O
+.	O
+
+No	O
+statistically	O
+significant	O
+changes	O
+in	O
+behavior	O
+or	O
+receptor	O
+binding	O
+were	O
+found	O
+in	O
+PD	O
+males	O
+with	O
+the	O
+exception	O
+of	O
+increased	O
+(	O
+3	O
+)	O
+H	B-Chemical
+-	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+binding	O
+in	O
+cortex	O
+.	O
+
+This	O
+animal	O
+model	O
+may	O
+be	O
+useful	O
+to	O
+explore	O
+the	O
+mechanisms	O
+by	O
+which	O
+prenatal	O
+nutritional	B-Disease
+deficiency	I-Disease
+enhances	O
+risk	O
+for	O
+schizophrenia	B-Disease
+in	O
+humans	O
+and	O
+may	O
+also	O
+have	O
+implications	O
+for	O
+developmental	O
+processes	O
+leading	O
+to	O
+differential	O
+sensitivity	O
+to	O
+drugs	O
+of	O
+abuse	O
+.	O
+
+Adverse	O
+effects	O
+of	O
+topical	O
+papaverine	B-Chemical
+on	O
+auditory	O
+nerve	O
+function	O
+.	O
+
+BACKGROUND	O
+:	O
+Papaverine	B-Chemical
+hydrochloride	I-Chemical
+is	O
+a	O
+direct	O
+-	O
+acting	O
+vasodilator	O
+used	O
+to	O
+manage	O
+vasospasm	B-Disease
+during	O
+various	O
+neurosurgical	O
+operations	O
+.	O
+
+Transient	O
+cranial	B-Disease
+nerve	I-Disease
+dysfunction	I-Disease
+has	O
+been	O
+described	O
+in	O
+a	O
+few	O
+cases	O
+with	O
+topical	O
+papaverine	B-Chemical
+.	O
+
+This	O
+study	O
+supports	O
+previous	O
+reports	O
+and	O
+provides	O
+neurophysiological	O
+evidence	O
+of	O
+an	O
+adverse	O
+effect	O
+on	O
+the	O
+auditory	O
+nerve	O
+.	O
+
+METHODS	O
+:	O
+We	O
+conducted	O
+a	O
+retrospective	O
+review	O
+of	O
+70	O
+consecutive	O
+microvascular	O
+decompression	O
+operations	O
+and	O
+studied	O
+those	O
+patients	O
+who	O
+received	O
+topical	O
+papaverine	B-Chemical
+for	O
+vasospasm	B-Disease
+.	O
+
+Topical	O
+papaverine	B-Chemical
+was	O
+used	O
+as	O
+a	O
+direct	O
+therapeutic	O
+action	O
+to	O
+manage	O
+vasospasm	B-Disease
+in	O
+a	O
+total	O
+of	O
+11	O
+patients	O
+.	O
+
+The	O
+timing	O
+of	O
+papaverine	B-Chemical
+application	O
+and	O
+ongoing	O
+operative	O
+events	O
+was	O
+reviewed	O
+relative	O
+to	O
+changes	O
+in	O
+neurophysiological	O
+recordings	O
+.	O
+
+Brainstem	O
+auditory	O
+evoked	O
+potentials	O
+(	O
+BAEPs	O
+)	O
+were	O
+routinely	O
+used	O
+to	O
+monitor	O
+cochlear	O
+nerve	O
+function	O
+during	O
+these	O
+operations	O
+.	O
+
+FINDINGS	O
+:	O
+A	O
+temporal	O
+relationship	O
+was	O
+found	O
+between	O
+topical	O
+papaverine	B-Chemical
+and	O
+BAEP	O
+changes	O
+leading	O
+to	O
+complete	O
+waveform	O
+loss	O
+.	O
+
+The	O
+average	O
+temporal	O
+delay	O
+between	O
+papaverine	B-Chemical
+and	O
+the	O
+onset	O
+of	O
+an	O
+adverse	O
+BAEP	O
+change	O
+was	O
+5	O
+min	O
+.	O
+
+In	O
+10	O
+of	O
+11	O
+patients	O
+,	O
+BAEP	O
+waves	O
+II	O
+/	O
+III	O
+-	O
+V	O
+completely	O
+disappeared	O
+within	O
+2	O
+to	O
+25	O
+min	O
+after	O
+papaverine	B-Chemical
+.	O
+
+Eight	O
+of	O
+these	O
+10	O
+patients	O
+had	O
+complete	O
+loss	O
+of	O
+BAEP	O
+waveforms	O
+within	O
+10	O
+min	O
+.	O
+
+One	O
+patient	O
+showed	O
+no	O
+recovery	O
+of	O
+later	O
+waves	O
+and	O
+a	O
+delayed	O
+profound	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+.	O
+
+The	O
+average	O
+recovery	O
+time	O
+of	O
+BAEP	O
+waveforms	O
+to	O
+pre	O
+-	O
+papaverine	B-Chemical
+baseline	O
+values	O
+was	O
+39	O
+min	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Topical	O
+papaverine	B-Chemical
+for	O
+the	O
+treatment	O
+of	O
+vasospasm	B-Disease
+was	O
+associated	O
+with	O
+the	O
+onset	O
+of	O
+a	O
+transient	O
+disturbance	O
+in	O
+neurophysiological	O
+function	O
+of	O
+the	O
+ascending	O
+auditory	O
+brainstem	O
+pathway	O
+.	O
+
+The	O
+complete	O
+disappearance	O
+of	O
+BAEP	O
+waveforms	O
+with	O
+a	O
+consistent	O
+temporal	O
+delay	O
+suggests	O
+a	O
+possible	O
+adverse	B-Disease
+effect	I-Disease
+on	I-Disease
+the	I-Disease
+proximal	I-Disease
+eighth	I-Disease
+nerve	I-Disease
+.	O
+
+Recommendations	O
+to	O
+avoid	O
+potential	O
+cranial	B-Disease
+nerve	I-Disease
+deficits	I-Disease
+from	O
+papaverine	B-Chemical
+are	O
+provided	O
+.	O
+
+Simvastatin	B-Chemical
+-	I-Chemical
+ezetimibe	I-Chemical
+-	O
+induced	O
+hepatic	B-Disease
+failure	I-Disease
+necessitating	O
+liver	O
+transplantation	O
+.	O
+
+Abstract	O
+Serum	O
+aminotransferase	O
+elevations	O
+are	O
+a	O
+commonly	O
+known	O
+adverse	O
+effect	O
+of	O
+3	O
+-	O
+hydroxy	O
+-	O
+3	O
+-	O
+methylglutaryl	O
+coenzyme	O
+A	O
+reductase	O
+inhibitor	O
+(	O
+statin	B-Chemical
+)	O
+therapy	O
+.	O
+
+However	O
+,	O
+hepatotoxic	B-Disease
+events	O
+have	O
+not	O
+been	O
+widely	O
+published	O
+with	O
+ezetimibe	B-Chemical
+or	O
+the	O
+combination	O
+agent	O
+simvastatin	B-Chemical
+-	I-Chemical
+ezetimibe	I-Chemical
+.	O
+
+We	O
+describe	O
+a	O
+70	O
+-	O
+year	O
+-	O
+old	O
+Hispanic	O
+woman	O
+who	O
+developed	O
+fulminant	B-Disease
+hepatic	I-Disease
+failure	I-Disease
+necessitating	O
+liver	O
+transplantation	O
+10	O
+weeks	O
+after	O
+conversion	O
+from	O
+simvastatin	B-Chemical
+40	O
+mg	O
+/	O
+day	O
+to	O
+simvastatin	B-Chemical
+10	I-Chemical
+mg	I-Chemical
+-	I-Chemical
+ezetimibe	I-Chemical
+40	I-Chemical
+mg	I-Chemical
+/	O
+day	O
+.	O
+
+The	O
+patient	O
+'	O
+s	O
+lipid	O
+panel	O
+had	O
+been	O
+maintained	O
+with	O
+simvastatin	B-Chemical
+for	O
+18	O
+months	O
+before	O
+the	O
+conversion	O
+without	O
+evidence	O
+of	O
+hepatotoxicity	B-Disease
+.	O
+
+A	O
+routine	O
+laboratory	O
+work	O
+-	O
+up	O
+10	O
+weeks	O
+after	O
+conversion	O
+revealed	O
+elevated	O
+serum	O
+aminotransferase	O
+levels	O
+.	O
+
+Simvastatinezetimibe	B-Chemical
+and	O
+escitalopram	B-Chemical
+(	O
+which	O
+she	O
+was	O
+taking	O
+for	O
+depression	B-Disease
+)	O
+were	O
+discontinued	O
+,	O
+and	O
+other	O
+potential	O
+causes	O
+of	O
+hepatotoxicity	B-Disease
+were	O
+excluded	O
+.	O
+
+A	O
+repeat	O
+work	O
+-	O
+up	O
+revealed	O
+further	O
+elevations	O
+in	O
+aminotransferase	O
+levels	O
+,	O
+and	O
+liver	O
+biopsy	O
+revealed	O
+evidence	O
+of	O
+moderate	O
+-	O
+to	O
+-	O
+severe	O
+drug	B-Disease
+toxicity	I-Disease
+.	O
+
+She	O
+underwent	O
+liver	O
+transplantation	O
+with	O
+an	O
+uneventful	O
+postoperative	O
+course	O
+.	O
+
+Her	O
+aminotransferase	O
+levels	O
+returned	O
+to	O
+normal	O
+by	O
+postoperative	O
+day	O
+23	O
+,	O
+and	O
+her	O
+2	O
+-	O
+year	O
+follow	O
+-	O
+up	O
+showed	O
+no	O
+adverse	O
+events	O
+.	O
+
+Ezetimibe	B-Chemical
+undergoes	O
+extensive	O
+glucuronidation	O
+by	O
+uridine	B-Chemical
+diphosphate	I-Chemical
+glucoronosyltransferases	O
+(	O
+UGT	O
+)	O
+in	O
+the	O
+intestine	O
+and	O
+liver	O
+and	O
+may	O
+have	O
+inhibited	O
+the	O
+glucuronidation	O
+of	O
+simvastatin	B-Chemical
+hydroxy	I-Chemical
+acid	I-Chemical
+,	O
+resulting	O
+in	O
+increased	O
+simvastatin	B-Chemical
+exposure	O
+and	O
+subsequent	O
+hepatotoxicity	B-Disease
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+case	O
+report	O
+of	O
+simvastatin	B-Chemical
+-	I-Chemical
+ezetimibe	I-Chemical
+-	O
+induced	O
+liver	B-Disease
+failure	I-Disease
+that	O
+resulted	O
+in	O
+liver	O
+transplantation	O
+.	O
+
+We	O
+postulate	O
+that	O
+the	O
+mechanism	O
+of	O
+the	O
+simvastatinezetimibe	B-Chemical
+-	O
+induced	O
+hepatotoxicity	B-Disease
+is	O
+the	O
+increased	O
+simvastatin	B-Chemical
+exposure	O
+by	O
+ezetimibe	B-Chemical
+inhibition	O
+of	O
+UGT	O
+enzymes	O
+.	O
+
+Clinicians	O
+should	O
+be	O
+aware	O
+of	O
+potential	O
+hepatotoxicity	B-Disease
+with	O
+simvastatin	B-Chemical
+-	I-Chemical
+ezetimibe	I-Chemical
+especially	O
+in	O
+elderly	O
+patients	O
+and	O
+should	O
+carefully	O
+monitor	O
+serum	O
+aminotransferase	O
+levels	O
+when	O
+starting	O
+therapy	O
+and	O
+titrating	O
+the	O
+dosage	O
+.	O
+
+Massive	O
+proteinuria	B-Disease
+and	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+after	O
+oral	O
+bisphosphonate	B-Chemical
+(	O
+alendronate	B-Chemical
+)	O
+administration	O
+in	O
+a	O
+patient	O
+with	O
+focal	B-Disease
+segmental	I-Disease
+glomerulosclerosis	I-Disease
+.	O
+
+A	O
+61	O
+-	O
+year	O
+-	O
+old	O
+Japanese	O
+man	O
+with	O
+nephrotic	B-Disease
+syndrome	I-Disease
+due	O
+to	O
+focal	B-Disease
+segmental	I-Disease
+glomerulosclerosis	I-Disease
+was	O
+initially	O
+responding	O
+well	O
+to	O
+steroid	B-Chemical
+therapy	O
+.	O
+
+The	O
+amount	O
+of	O
+daily	O
+urinary	O
+protein	O
+decreased	O
+from	O
+15	O
+.	O
+6	O
+to	O
+2	O
+.	O
+8	O
+g	O
+.	O
+
+Within	O
+14	O
+days	O
+of	O
+the	O
+oral	O
+bisphosphonate	B-Chemical
+(	O
+alendronate	B-Chemical
+sodium	I-Chemical
+)	O
+administration	O
+,	O
+the	O
+amount	O
+of	O
+daily	O
+urinary	O
+protein	O
+increased	O
+rapidly	O
+up	O
+to	O
+12	O
+.	O
+8	O
+g	O
+with	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+.	O
+
+After	O
+discontinuing	O
+the	O
+oral	O
+alendronate	B-Chemical
+,	O
+the	O
+patient	O
+underwent	O
+six	O
+cycles	O
+of	O
+hemodialysis	O
+and	O
+four	O
+cycles	O
+of	O
+LDL	O
+apheresis	O
+.	O
+
+Urinary	O
+volume	O
+and	O
+serum	O
+creatinine	B-Chemical
+levels	O
+recovered	O
+to	O
+the	O
+normal	O
+range	O
+,	O
+with	O
+urinary	O
+protein	O
+disappearing	O
+completely	O
+within	O
+40	O
+days	O
+.	O
+
+This	O
+report	O
+demonstrates	O
+that	O
+not	O
+only	O
+intravenous	O
+,	O
+but	O
+also	O
+oral	O
+bisphosphonates	B-Chemical
+can	O
+aggravate	O
+proteinuria	B-Disease
+and	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+.	O
+
+Serum	O
+-	O
+and	O
+glucocorticoid	O
+-	O
+inducible	O
+kinase	O
+1	O
+in	O
+doxorubicin	B-Chemical
+-	O
+induced	O
+nephrotic	B-Disease
+syndrome	I-Disease
+.	O
+
+Doxorubicin	B-Chemical
+-	O
+induced	O
+nephropathy	B-Disease
+leads	O
+to	O
+epithelial	O
+sodium	B-Chemical
+channel	O
+(	O
+ENaC	O
+)	O
+-	O
+dependent	O
+volume	B-Disease
+retention	I-Disease
+and	O
+renal	O
+fibrosis	B-Disease
+.	O
+
+The	O
+aldosterone	B-Chemical
+-	O
+sensitive	O
+serum	O
+-	O
+and	O
+glucocorticoid	O
+-	O
+inducible	O
+kinase	O
+SGK1	O
+has	O
+been	O
+shown	O
+to	O
+participate	O
+in	O
+the	O
+stimulation	O
+of	O
+ENaC	O
+and	O
+to	O
+mediate	O
+renal	O
+fibrosis	B-Disease
+following	O
+mineralocorticoid	O
+and	O
+salt	O
+excess	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+performed	O
+to	O
+elucidate	O
+the	O
+role	O
+of	O
+SGK1	O
+in	O
+the	O
+volume	B-Disease
+retention	I-Disease
+and	O
+fibrosis	B-Disease
+during	O
+nephrotic	B-Disease
+syndrome	I-Disease
+.	O
+
+To	O
+this	O
+end	O
+,	O
+doxorubicin	B-Chemical
+(	O
+15	O
+mug	O
+/	O
+g	O
+body	O
+wt	O
+)	O
+was	O
+injected	O
+intravenously	O
+into	O
+gene	O
+-	O
+targeted	O
+mice	O
+lacking	O
+SGK1	O
+(	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+)	O
+and	O
+their	O
+wild	O
+-	O
+type	O
+littermates	O
+(	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+)	O
+.	O
+
+Doxorubicin	B-Chemical
+treatment	O
+resulted	O
+in	O
+heavy	O
+proteinuria	B-Disease
+(	O
+>	O
+100	O
+mg	O
+protein	O
+/	O
+mg	O
+crea	O
+)	O
+in	O
+15	O
+/	O
+44	O
+of	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+and	O
+15	O
+/	O
+44	O
+of	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+leading	O
+to	O
+severe	O
+nephrotic	B-Disease
+syndrome	I-Disease
+with	O
+ascites	B-Disease
+,	O
+lipidemia	B-Disease
+,	O
+and	O
+hypoalbuminemia	B-Disease
+in	O
+both	O
+genotypes	O
+.	O
+
+Plasma	O
+aldosterone	B-Chemical
+levels	O
+increased	O
+in	O
+nephrotic	B-Disease
+mice	O
+of	O
+both	O
+genotypes	O
+and	O
+was	O
+followed	O
+by	O
+increased	O
+SGK1	O
+protein	O
+expression	O
+in	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+mice	O
+.	O
+
+Urinary	O
+sodium	B-Chemical
+excretion	O
+reached	O
+signficantly	O
+lower	O
+values	O
+in	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+mice	O
+(	O
+15	O
++	O
+/	O
+-	O
+5	O
+mumol	O
+/	O
+mg	O
+crea	O
+)	O
+than	O
+in	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+(	O
+35	O
++	O
+/	O
+-	O
+5	O
+mumol	O
+/	O
+mg	O
+crea	O
+)	O
+and	O
+was	O
+associated	O
+with	O
+a	O
+significantly	O
+higher	O
+body	O
+weight	B-Disease
+gain	I-Disease
+in	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+compared	O
+with	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+(	O
++	O
+6	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+7	O
+vs	O
+.	O
++	O
+4	O
+.	O
+1	O
++	O
+/	O
+-	O
+0	O
+.	O
+8	O
+g	O
+)	O
+.	O
+
+During	O
+the	O
+course	O
+of	O
+nephrotic	B-Disease
+syndrome	I-Disease
+,	O
+serum	O
+urea	B-Chemical
+concentrations	O
+increased	O
+significantly	O
+faster	O
+in	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+than	O
+in	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+mice	O
+leading	O
+to	O
+uremia	B-Disease
+and	O
+a	O
+reduced	O
+median	O
+survival	O
+in	O
+sgk1	O
+(	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+(	O
+29	O
+vs	O
+.	O
+40	O
+days	O
+in	O
+sgk1	O
+(	O
++	O
+/	O
++	O
+)	O
+mice	O
+)	O
+.	O
+
+In	O
+conclusion	O
+,	O
+gene	O
+-	O
+targeted	O
+mice	O
+lacking	O
+SGK1	O
+showed	O
+blunted	O
+volume	B-Disease
+retention	I-Disease
+,	O
+yet	O
+were	O
+not	O
+protected	O
+against	O
+renal	O
+fibrosis	B-Disease
+during	O
+experimental	O
+nephrotic	B-Disease
+syndrome	I-Disease
+.	O
+
+Severe	O
+thrombocytopenia	B-Disease
+and	O
+haemolytic	B-Disease
+anaemia	I-Disease
+associated	O
+with	O
+ciprofloxacin	B-Chemical
+:	O
+a	O
+case	O
+report	O
+with	O
+fatal	O
+outcome	O
+.	O
+
+Haematological	O
+adverse	O
+reactions	O
+associated	O
+with	O
+fatal	O
+outcome	O
+are	O
+rare	O
+during	O
+treatment	O
+with	O
+ciprofloxacin	B-Chemical
+.	O
+
+A	O
+30	O
+-	O
+year	O
+old	O
+Caucasian	O
+man	O
+reported	O
+with	O
+abdominal	B-Disease
+pain	I-Disease
+and	O
+jaundice	B-Disease
+after	O
+3	O
+-	O
+day	O
+administration	O
+of	O
+oral	O
+ciprofloxacin	B-Chemical
+for	O
+a	O
+suspect	O
+of	O
+urinary	B-Disease
+tract	I-Disease
+infection	I-Disease
+.	O
+
+Clinical	O
+evaluations	O
+suggested	O
+an	O
+initial	O
+diagnosis	O
+of	O
+severe	O
+thrombocytopenia	B-Disease
+and	O
+haemolysis	B-Disease
+.	O
+
+The	O
+patient	O
+progressively	O
+developed	O
+petechiae	B-Disease
+and	O
+purpura	B-Disease
+on	O
+thorax	O
+and	O
+lower	O
+limbs	O
+.	O
+
+Despite	O
+pharmacological	O
+and	O
+supportive	O
+interventions	O
+,	O
+laboratory	O
+parameters	O
+worsened	O
+and	O
+the	O
+patient	O
+died	O
+17	O
+hours	O
+after	O
+admission	O
+.	O
+
+An	O
+accurate	O
+autopsy	O
+revealed	O
+most	O
+organs	O
+with	O
+diffuse	O
+petechial	O
+haemorrhages	B-Disease
+.	O
+
+No	O
+signs	O
+of	O
+bone	B-Disease
+marrow	I-Disease
+depression	I-Disease
+were	O
+found	O
+.	O
+
+No	O
+thrombi	B-Disease
+or	O
+signs	O
+of	O
+microangiopathies	B-Disease
+were	O
+observed	O
+in	O
+arterial	O
+vessels	O
+.	O
+
+Blood	O
+and	O
+urine	O
+cultures	O
+did	O
+not	O
+show	O
+any	O
+bacterial	O
+growth	O
+.	O
+
+This	O
+case	O
+report	O
+shows	O
+that	O
+ciprofloxacin	B-Chemical
+may	O
+precipitate	O
+life	O
+-	O
+threatening	O
+thrombocytopenia	B-Disease
+and	O
+haemolytic	B-Disease
+anaemia	I-Disease
+,	O
+even	O
+in	O
+the	O
+early	O
+phases	O
+of	O
+treatment	O
+and	O
+without	O
+apparent	O
+previous	O
+exposures	O
+.	O
+
+Alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+prevents	O
+mitochondrial	B-Disease
+damage	I-Disease
+and	O
+neurotoxicity	B-Disease
+in	O
+experimental	O
+chemotherapy	O
+neuropathy	B-Disease
+.	O
+
+The	O
+study	O
+investigates	O
+if	O
+alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+is	O
+neuroprotective	O
+against	O
+chemotherapy	O
+induced	O
+neurotoxicity	B-Disease
+,	O
+if	O
+mitochondrial	B-Disease
+damage	I-Disease
+plays	O
+a	O
+critical	O
+role	O
+in	O
+toxic	B-Disease
+neurodegenerative	I-Disease
+cascade	I-Disease
+,	O
+and	O
+if	O
+neuroprotective	O
+effects	O
+of	O
+alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+depend	O
+on	O
+mitochondria	O
+protection	O
+.	O
+
+We	O
+used	O
+an	O
+in	O
+vitro	O
+model	O
+of	O
+chemotherapy	O
+induced	O
+peripheral	B-Disease
+neuropathy	I-Disease
+that	O
+closely	O
+mimic	O
+the	O
+in	O
+vivo	O
+condition	O
+by	O
+exposing	O
+primary	O
+cultures	O
+of	O
+dorsal	O
+root	O
+ganglion	O
+(	O
+DRG	O
+)	O
+sensory	O
+neurons	O
+to	O
+paclitaxel	B-Chemical
+and	O
+cisplatin	B-Chemical
+,	O
+two	O
+widely	O
+used	O
+and	O
+highly	O
+effective	O
+chemotherapeutic	O
+drugs	O
+.	O
+
+This	O
+approach	O
+allowed	O
+investigating	O
+the	O
+efficacy	O
+of	O
+alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+in	O
+preventing	O
+axonal	B-Disease
+damage	I-Disease
+and	O
+apoptosis	O
+and	O
+the	O
+function	O
+and	O
+ultrastructural	O
+morphology	O
+of	O
+mitochondria	O
+after	O
+exposure	O
+to	O
+toxic	O
+agents	O
+and	O
+alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+.	O
+
+Our	O
+results	O
+demonstrate	O
+that	O
+both	O
+cisplatin	B-Chemical
+and	O
+paclitaxel	B-Chemical
+cause	O
+early	O
+mitochondrial	B-Disease
+impairment	I-Disease
+with	O
+loss	O
+of	O
+membrane	O
+potential	O
+and	O
+induction	O
+of	O
+autophagic	O
+vacuoles	O
+in	O
+neurons	O
+.	O
+
+Alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+exerts	O
+neuroprotective	O
+effects	O
+against	O
+chemotherapy	O
+induced	O
+neurotoxicity	B-Disease
+in	O
+sensory	O
+neurons	O
+:	O
+it	O
+rescues	O
+the	O
+mitochondrial	B-Disease
+toxicity	I-Disease
+and	O
+induces	O
+the	O
+expression	O
+of	O
+frataxin	O
+,	O
+an	O
+essential	O
+mitochondrial	O
+protein	O
+with	O
+anti	O
+-	O
+oxidant	O
+and	O
+chaperone	O
+properties	O
+.	O
+
+In	O
+conclusion	O
+mitochondrial	B-Disease
+toxicity	I-Disease
+is	O
+an	O
+early	O
+common	O
+event	O
+both	O
+in	O
+paclitaxel	B-Chemical
+and	O
+cisplatin	B-Chemical
+induced	O
+neurotoxicity	B-Disease
+.	O
+
+Alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+protects	O
+sensory	O
+neurons	O
+through	O
+its	O
+anti	O
+-	O
+oxidant	O
+and	O
+mitochondrial	O
+regulatory	O
+functions	O
+,	O
+possibly	O
+inducing	O
+the	O
+expression	O
+of	O
+frataxin	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+alpha	B-Chemical
+-	I-Chemical
+lipoic	I-Chemical
+acid	I-Chemical
+might	O
+reduce	O
+the	O
+risk	O
+of	O
+developing	O
+peripheral	B-Disease
+nerve	I-Disease
+toxicity	I-Disease
+in	O
+patients	O
+undergoing	O
+chemotherapy	O
+and	O
+encourage	O
+further	O
+confirmatory	O
+clinical	O
+trials	O
+.	O
+
+Toxicity	B-Disease
+in	O
+rhesus	O
+monkeys	O
+following	O
+administration	O
+of	O
+the	O
+8	B-Chemical
+-	I-Chemical
+aminoquinoline	I-Chemical
+8	B-Chemical
+-	I-Chemical
+[	I-Chemical
+(	I-Chemical
+4	I-Chemical
+-	I-Chemical
+amino	I-Chemical
+-	I-Chemical
+l	I-Chemical
+-	I-Chemical
+methylbutyl	I-Chemical
+)	I-Chemical
+amino	I-Chemical
+]	I-Chemical
+-	I-Chemical
+5	I-Chemical
+-	I-Chemical
+(	I-Chemical
+l	I-Chemical
+-	I-Chemical
+hexyloxy	I-Chemical
+)	I-Chemical
+-	I-Chemical
+6	I-Chemical
+-	I-Chemical
+methoxy	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+methylquinoline	I-Chemical
+(	O
+WR242511	B-Chemical
+)	O
+.	O
+
+INTRODUCTION	O
+:	O
+Many	O
+substances	O
+that	O
+form	O
+methemoglobin	O
+(	O
+MHb	O
+)	O
+effectively	O
+counter	O
+cyanide	O
+(	O
+CN	O
+)	O
+toxicity	B-Disease
+.	O
+
+Although	O
+MHb	O
+formers	O
+are	O
+generally	O
+applied	O
+as	O
+treatments	O
+for	O
+CN	O
+poisoning	B-Disease
+,	O
+it	O
+has	O
+been	O
+proposed	O
+that	O
+a	O
+stable	O
+,	O
+long	O
+-	O
+acting	O
+MHb	O
+former	O
+could	O
+serve	O
+as	O
+a	O
+CN	O
+pretreatment	O
+.	O
+
+Using	O
+this	O
+rationale	O
+,	O
+the	O
+8	B-Chemical
+-	I-Chemical
+aminoquinoline	I-Chemical
+WR242511	B-Chemical
+,	O
+a	O
+potent	O
+long	O
+-	O
+lasting	O
+MHb	O
+former	O
+in	O
+rodents	O
+and	O
+beagle	O
+dogs	O
+,	O
+was	O
+studied	O
+in	O
+the	O
+rhesus	O
+monkey	O
+for	O
+advanced	O
+development	O
+as	O
+a	O
+potential	O
+CN	O
+pretreatment	O
+.	O
+
+METHODS	O
+:	O
+In	O
+this	O
+study	O
+,	O
+WR242511	B-Chemical
+was	O
+administered	O
+intravenously	O
+(	O
+IV	O
+)	O
+in	O
+2	O
+female	O
+and	O
+4	O
+male	O
+rhesus	O
+monkeys	O
+in	O
+doses	O
+of	O
+3	O
+.	O
+5	O
+and	O
+/	O
+or	O
+7	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+;	O
+a	O
+single	O
+male	O
+also	O
+received	O
+WR242511	B-Chemical
+orally	O
+(	O
+PO	O
+)	O
+at	O
+7	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+.	O
+
+Health	O
+status	O
+and	O
+MHb	O
+levels	O
+were	O
+monitored	O
+following	O
+exposure	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+selected	O
+doses	O
+of	O
+WR242511	B-Chemical
+,	O
+which	O
+produced	O
+significant	O
+methemoglobinemia	B-Disease
+in	O
+beagle	O
+dogs	O
+in	O
+earlier	O
+studies	O
+conducted	O
+elsewhere	O
+,	O
+produced	O
+very	O
+little	O
+MHb	O
+(	O
+mean	O
+<	O
+2	O
+.	O
+0	O
+%	O
+)	O
+in	O
+the	O
+rhesus	O
+monkey	O
+.	O
+
+Furthermore	O
+,	O
+transient	O
+hemoglobinuria	B-Disease
+was	O
+noted	O
+approximately	O
+60	O
+minutes	O
+postinjection	O
+of	O
+WR242511	B-Chemical
+(	O
+3	O
+.	O
+5	O
+or	O
+7	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+and	O
+2	O
+lethalities	O
+occurred	O
+(	O
+one	O
+IV	O
+and	O
+one	O
+PO	O
+)	O
+following	O
+the	O
+7	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+dose	O
+.	O
+
+Myoglobinuria	B-Disease
+was	O
+also	O
+observed	O
+following	O
+the	O
+7	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+dose	O
+.	O
+
+Histopathology	O
+analyses	O
+in	O
+the	O
+2	O
+animals	O
+that	O
+died	O
+revealed	O
+liver	B-Disease
+and	I-Disease
+kidney	I-Disease
+toxicity	I-Disease
+,	O
+with	O
+greater	O
+severity	O
+in	O
+the	O
+orally	O
+-	O
+treated	O
+animal	O
+.	O
+
+CONCLUSIONS	O
+:	O
+These	O
+data	O
+demonstrate	O
+direct	O
+and	O
+/	O
+or	O
+indirect	O
+drug	O
+-	O
+induced	O
+toxicity	B-Disease
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+WR242511	B-Chemical
+should	O
+not	O
+be	O
+pursued	O
+as	O
+a	O
+pretreatment	O
+for	O
+CN	O
+poisoning	B-Disease
+unless	O
+the	O
+anti	O
+-	O
+CN	O
+characteristics	O
+of	O
+this	O
+compound	O
+can	O
+be	O
+successfully	O
+dissociated	O
+from	O
+those	O
+producing	O
+undesirable	O
+toxicity	B-Disease
+.	O
+
+Repetitive	O
+transcranial	O
+magnetic	O
+stimulation	O
+for	O
+levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+in	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+In	O
+a	O
+placebo	O
+-	O
+controlled	O
+,	O
+single	O
+-	O
+blinded	O
+,	O
+crossover	O
+study	O
+,	O
+we	O
+assessed	O
+the	O
+effect	O
+of	O
+"	O
+real	O
+"	O
+repetitive	O
+transcranial	O
+magnetic	O
+stimulation	O
+(	O
+rTMS	O
+)	O
+versus	O
+"	O
+sham	O
+"	O
+rTMS	O
+(	O
+placebo	O
+)	O
+on	O
+peak	O
+dose	O
+dyskinesias	B-Disease
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+.	O
+
+Ten	O
+patients	O
+with	O
+PD	B-Disease
+and	O
+prominent	O
+dyskinesias	B-Disease
+had	O
+rTMS	O
+(	O
+1	O
+,	O
+800	O
+pulses	O
+;	O
+1	O
+Hz	O
+rate	O
+)	O
+delivered	O
+over	O
+the	O
+motor	O
+cortex	O
+for	O
+4	O
+consecutive	O
+days	O
+twice	O
+,	O
+once	O
+real	O
+stimuli	O
+and	O
+once	O
+sham	O
+stimulation	O
+were	O
+used	O
+;	O
+evaluations	O
+were	O
+done	O
+at	O
+the	O
+baseline	O
+and	O
+1	O
+day	O
+after	O
+the	O
+end	O
+of	O
+each	O
+of	O
+the	O
+treatment	O
+series	O
+.	O
+
+Direct	O
+comparison	O
+between	O
+sham	O
+and	O
+real	O
+rTMS	O
+effects	O
+showed	O
+no	O
+significant	O
+difference	O
+in	O
+clinician	O
+-	O
+assessed	O
+dyskinesia	B-Disease
+severity	O
+.	O
+
+However	O
+,	O
+comparison	O
+with	O
+the	O
+baseline	O
+showed	O
+small	O
+but	O
+significant	O
+reduction	O
+in	O
+dyskinesia	B-Disease
+severity	O
+following	O
+real	O
+rTMS	O
+but	O
+not	O
+placebo	O
+.	O
+
+The	O
+major	O
+effect	O
+was	O
+on	O
+dystonia	B-Disease
+subscore	O
+.	O
+
+Similarly	O
+,	O
+in	O
+patient	O
+diaries	O
+,	O
+although	O
+both	O
+treatments	O
+caused	O
+reduction	O
+in	O
+subjective	O
+dyskinesia	B-Disease
+scores	O
+during	O
+the	O
+days	O
+of	O
+intervention	O
+,	O
+the	O
+effect	O
+was	O
+sustained	O
+for	O
+3	O
+days	O
+after	O
+the	O
+intervention	O
+for	O
+the	O
+real	O
+rTMS	O
+only	O
+.	O
+
+Following	O
+rTMS	O
+,	O
+no	O
+side	O
+effects	O
+and	O
+no	O
+adverse	O
+effects	O
+on	O
+motor	O
+function	O
+and	O
+PD	B-Disease
+symptoms	O
+were	O
+noted	O
+.	O
+
+The	O
+results	O
+suggest	O
+the	O
+existence	O
+of	O
+residual	O
+beneficial	O
+clinical	O
+aftereffects	O
+of	O
+consecutive	O
+daily	O
+applications	O
+of	O
+low	O
+-	O
+frequency	O
+rTMS	O
+on	O
+dyskinesias	B-Disease
+in	O
+PD	B-Disease
+.	O
+
+The	O
+effects	O
+may	O
+be	O
+further	O
+exploited	O
+for	O
+potential	O
+therapeutic	O
+uses	O
+.	O
+
+Intracavernous	O
+epinephrine	B-Chemical
+:	O
+a	O
+minimally	O
+invasive	O
+treatment	O
+for	O
+priapism	B-Disease
+in	O
+the	O
+emergency	O
+department	O
+.	O
+
+Priapism	B-Disease
+is	O
+the	O
+prolonged	O
+erection	O
+of	O
+the	O
+penis	O
+in	O
+the	O
+absence	O
+of	O
+sexual	O
+arousal	O
+.	O
+
+A	O
+45	O
+-	O
+year	O
+-	O
+old	O
+man	O
+,	O
+an	O
+admitted	O
+frequent	O
+cocaine	B-Chemical
+user	O
+,	O
+presented	O
+to	O
+the	O
+Emergency	O
+Department	O
+(	O
+ED	O
+)	O
+on	O
+two	O
+separate	O
+occasions	O
+with	O
+a	O
+history	O
+of	O
+priapism	B-Disease
+after	O
+cocaine	B-Chemical
+use	O
+.	O
+
+The	O
+management	O
+options	O
+in	O
+the	O
+ED	O
+,	O
+as	O
+exemplified	O
+by	O
+four	O
+individual	O
+case	O
+reports	O
+,	O
+in	O
+particular	O
+the	O
+use	O
+of	O
+a	O
+minimally	O
+invasive	O
+method	O
+of	O
+intracorporal	O
+epinephrine	B-Chemical
+instillation	O
+,	O
+are	O
+discussed	O
+.	O
+
+Prophylactic	O
+use	O
+of	O
+lamivudine	B-Chemical
+with	O
+chronic	O
+immunosuppressive	O
+therapy	O
+for	O
+rheumatologic	B-Disease
+disorders	I-Disease
+.	O
+
+The	O
+objective	O
+of	O
+this	O
+study	O
+was	O
+to	O
+report	O
+our	O
+experience	O
+concerning	O
+the	O
+effectiveness	O
+of	O
+the	O
+prophylactic	O
+administration	O
+of	O
+lamivudine	B-Chemical
+in	O
+hepatitis	B-Chemical
+B	I-Chemical
+virus	I-Chemical
+surface	I-Chemical
+antigen	I-Chemical
+(	O
+HBs	B-Chemical
+Ag	I-Chemical
+)	O
+positive	O
+patients	O
+with	O
+rheumatologic	B-Disease
+disease	I-Disease
+.	O
+
+From	O
+June	O
+2004	O
+to	O
+October	O
+2006	O
+,	O
+11	O
+HBs	B-Chemical
+Ag	I-Chemical
+positive	O
+patients	O
+with	O
+rheumatologic	B-Disease
+diseases	I-Disease
+,	O
+who	O
+were	O
+on	O
+both	O
+immunosuppressive	O
+and	O
+prophylactic	O
+lamivudine	B-Chemical
+therapies	O
+,	O
+were	O
+retrospectively	O
+assessed	O
+.	O
+
+Liver	O
+function	O
+tests	O
+,	O
+hepatitis	B-Disease
+B	I-Disease
+virus	O
+(	O
+HBV	O
+)	O
+serologic	O
+markers	O
+,	O
+and	O
+HBV	O
+DNA	O
+levels	O
+of	O
+the	O
+patients	O
+during	O
+follow	O
+-	O
+up	O
+were	O
+obtained	O
+from	O
+hospital	O
+file	O
+records	O
+.	O
+
+Eleven	O
+patients	O
+(	O
+six	O
+male	O
+)	O
+with	O
+median	O
+age	O
+47	O
+years	O
+(	O
+range	O
+27	O
+-	O
+73	O
+)	O
+,	O
+median	O
+disease	O
+duration	O
+50	O
+months	O
+(	O
+range	O
+9	O
+-	O
+178	O
+)	O
+and	O
+median	O
+follow	O
+-	O
+up	O
+period	O
+of	O
+patients	O
+13	O
+.	O
+8	O
+months	O
+(	O
+range	O
+5	O
+-	O
+27	O
+)	O
+were	O
+enrolled	O
+in	O
+this	O
+study	O
+.	O
+
+Lamivudine	B-Chemical
+therapy	O
+was	O
+started	O
+3	O
+-	O
+7	O
+days	O
+prior	O
+to	O
+immunosuppressive	O
+therapy	O
+in	O
+all	O
+patients	O
+.	O
+
+Baseline	O
+,	O
+liver	O
+function	O
+tests	O
+were	O
+elevated	O
+in	O
+two	O
+patients	O
+(	O
+fourth	O
+patient	O
+:	O
+ALT	O
+:	O
+122	O
+IU	O
+/	O
+l	O
+,	O
+AST	O
+:	O
+111	O
+IU	O
+/	O
+l	O
+,	O
+tenth	O
+patient	O
+:	O
+ALT	O
+:	O
+294	O
+IU	O
+/	O
+l	O
+,	O
+AST	O
+:	O
+274	O
+IU	O
+/	O
+l	O
+,	O
+with	O
+minimal	O
+changes	O
+in	O
+the	O
+liver	O
+biopsy	O
+in	O
+both	O
+)	O
+.	O
+
+Shortly	O
+after	O
+treatment	O
+their	O
+tests	O
+normalized	O
+and	O
+during	O
+follow	O
+-	O
+up	O
+period	O
+none	O
+of	O
+the	O
+patients	O
+had	O
+abnormal	B-Disease
+liver	I-Disease
+function	I-Disease
+tests	O
+.	O
+
+In	O
+four	O
+patients	O
+HBV	O
+DNA	O
+levels	O
+were	O
+higher	O
+than	O
+normal	O
+at	O
+baseline	O
+.	O
+
+Two	O
+of	O
+these	O
+normalized	O
+and	O
+the	O
+others	O
+increased	O
+later	O
+.	O
+
+In	O
+three	O
+additional	O
+patients	O
+,	O
+HBV	O
+DNA	O
+levels	O
+were	O
+increased	O
+during	O
+follow	O
+-	O
+up	O
+.	O
+
+None	O
+of	O
+the	O
+patients	O
+had	O
+significant	O
+clinical	O
+sings	O
+of	O
+HBV	O
+activation	O
+.	O
+
+Lamivudine	B-Chemical
+was	O
+well	O
+tolerated	O
+and	O
+was	O
+continued	O
+in	O
+all	O
+patients	O
+.	O
+
+Prophylactic	O
+administration	O
+of	O
+lamivudine	B-Chemical
+in	O
+patients	O
+who	O
+required	O
+immunosuppressive	O
+therapy	O
+seems	O
+to	O
+be	O
+safe	O
+,	O
+well	O
+tolerated	O
+and	O
+effective	O
+in	O
+preventing	O
+HBV	O
+reactivation	O
+.	O
+
+Effect	O
+of	O
+green	B-Chemical
+tea	I-Chemical
+and	O
+vitamin	B-Chemical
+E	I-Chemical
+combination	O
+in	O
+isoproterenol	B-Chemical
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+aimed	O
+to	O
+investigate	O
+the	O
+combined	O
+effects	O
+of	O
+green	B-Chemical
+tea	I-Chemical
+and	O
+vitamin	B-Chemical
+E	I-Chemical
+on	O
+heart	O
+weight	O
+,	O
+body	O
+weight	O
+,	O
+serum	O
+marker	O
+enzymes	O
+,	O
+lipid	O
+peroxidation	O
+,	O
+endogenous	O
+antioxidants	O
+and	O
+membrane	O
+bound	O
+ATPases	O
+in	O
+isoproterenol	B-Chemical
+(	O
+ISO	B-Chemical
+)	O
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Adult	O
+male	O
+albino	O
+rats	O
+,	O
+treated	O
+with	O
+ISO	B-Chemical
+(	O
+200	O
+mg	O
+/	O
+kg	O
+,	O
+s	O
+.	O
+c	O
+.	O
+)	O
+for	O
+2	O
+days	O
+at	O
+an	O
+interval	O
+of	O
+24	O
+h	O
+caused	O
+a	O
+significant	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+elevation	O
+of	O
+heart	O
+weight	O
+,	O
+serum	O
+marker	O
+enzymes	O
+,	O
+lipid	O
+peroxidation	O
+and	O
+Ca	B-Chemical
++	O
+2	O
+ATPase	O
+level	O
+whereas	O
+there	O
+was	O
+a	O
+significant	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+decrease	O
+in	O
+body	O
+weight	O
+,	O
+endogenous	O
+antioxidants	O
+,	O
+Na	B-Chemical
++	O
+/	O
+K	B-Chemical
++	O
+ATPase	O
+and	O
+Mg	B-Chemical
++	O
+2	O
+ATPase	O
+levels	O
+.	O
+
+Administration	O
+of	O
+green	B-Chemical
+tea	I-Chemical
+(	O
+100	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+,	O
+p	O
+.	O
+o	O
+.	O
+)	O
+and	O
+vitamin	B-Chemical
+E	I-Chemical
+(	O
+100	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+,	O
+p	O
+.	O
+o	O
+.	O
+)	O
+together	O
+for	O
+30	O
+consecutive	O
+days	O
+and	O
+challenged	O
+with	O
+ISO	B-Chemical
+on	O
+the	O
+day	O
+29th	O
+and	O
+30th	O
+,	O
+showed	O
+a	O
+significant	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+decrease	O
+in	O
+heart	O
+weight	O
+,	O
+serum	O
+marker	O
+enzymes	O
+,	O
+lipid	O
+peroxidation	O
+,	O
+Ca	B-Chemical
++	O
+2	O
+ATPase	O
+and	O
+a	O
+significant	O
+increase	O
+in	O
+the	O
+body	O
+weight	O
+,	O
+endogenous	O
+antioxidants	O
+,	O
+Na	B-Chemical
++	O
+/	O
+K	B-Chemical
++	O
+ATPase	O
+and	O
+Mg	B-Chemical
++	O
+2	O
+ATPase	O
+when	O
+compared	O
+with	O
+ISO	B-Chemical
+treated	O
+group	O
+and	O
+green	B-Chemical
+tea	I-Chemical
+or	O
+vitamin	B-Chemical
+E	I-Chemical
+alone	O
+treated	O
+groups	O
+.	O
+
+These	O
+findings	O
+indicate	O
+the	O
+synergistic	O
+protective	O
+effect	O
+of	O
+green	B-Chemical
+tea	I-Chemical
+and	O
+vitamin	B-Chemical
+E	I-Chemical
+during	O
+ISO	B-Chemical
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Irreversible	O
+damage	O
+to	O
+the	O
+medullary	O
+interstitium	O
+in	O
+experimental	O
+analgesic	O
+nephropathy	B-Disease
+in	O
+F344	O
+rats	O
+.	O
+
+Renal	B-Disease
+papillary	I-Disease
+necrosis	I-Disease
+(	O
+RPN	B-Disease
+)	O
+and	O
+a	O
+decreased	O
+urinary	O
+concentrating	O
+ability	O
+developed	O
+during	O
+continuous	O
+long	O
+-	O
+term	O
+treatment	O
+with	O
+aspirin	B-Chemical
+and	O
+paracetamol	B-Chemical
+in	O
+female	O
+Fischer	O
+344	O
+rats	O
+.	O
+
+Renal	O
+structure	O
+and	O
+concentrating	O
+ability	O
+were	O
+examined	O
+after	O
+a	O
+recovery	O
+period	O
+of	O
+up	O
+to	O
+18	O
+weeks	O
+,	O
+when	O
+no	O
+analgesics	O
+were	O
+given	O
+,	O
+to	O
+investigate	O
+whether	O
+the	O
+analgesic	O
+-	O
+induced	O
+changes	O
+were	O
+reversible	O
+.	O
+
+There	O
+was	O
+no	O
+evidence	O
+of	O
+repair	O
+to	O
+the	O
+damaged	O
+medullary	O
+interstitial	O
+matrix	O
+,	O
+or	O
+proliferation	O
+of	O
+remaining	O
+undamaged	O
+type	O
+1	O
+medullary	O
+interstitial	O
+cells	O
+after	O
+the	O
+recovery	O
+period	O
+following	O
+analgesic	O
+treatment	O
+.	O
+
+The	O
+recovery	O
+of	O
+urinary	O
+concentrating	O
+ability	O
+was	O
+related	O
+to	O
+the	O
+length	O
+of	O
+analgesic	O
+treatment	O
+and	O
+the	O
+extent	O
+of	O
+the	O
+resulting	O
+inner	O
+medullary	O
+structural	O
+damage	O
+.	O
+
+During	O
+the	O
+early	O
+stages	O
+of	O
+analgesic	O
+treatment	O
+,	O
+the	O
+changes	O
+in	O
+urinary	O
+concentrating	O
+ability	O
+were	O
+reversible	O
+,	O
+but	O
+after	O
+prolonged	O
+analgesic	O
+treatment	O
+,	O
+maximum	O
+urinary	O
+concentrating	O
+ability	O
+failed	O
+to	O
+recover	O
+.	O
+
+This	O
+study	O
+shows	O
+that	O
+prolonged	O
+analgesic	O
+treatment	O
+in	O
+Fischer	O
+344	O
+rats	O
+causes	O
+progressive	O
+and	O
+irreversible	O
+damage	O
+to	O
+the	O
+interstitial	O
+matrix	O
+and	O
+type	O
+1	O
+interstitial	O
+cells	O
+leading	O
+to	O
+RPN	B-Disease
+.	O
+
+The	O
+associated	O
+urinary	O
+concentrating	O
+defect	O
+is	O
+reversible	O
+only	O
+during	O
+the	O
+early	O
+stages	O
+of	O
+structural	O
+damage	O
+to	O
+the	O
+inner	O
+medulla	O
+.	O
+
+Testosterone	B-Chemical
+-	O
+dependent	O
+hypertension	B-Disease
+and	O
+upregulation	O
+of	O
+intrarenal	O
+angiotensinogen	O
+in	O
+Dahl	O
+salt	B-Chemical
+-	O
+sensitive	O
+rats	O
+.	O
+
+Blood	O
+pressure	O
+(	O
+BP	O
+)	O
+is	O
+more	O
+salt	B-Chemical
+sensitive	O
+in	O
+men	O
+than	O
+in	O
+premenopausal	O
+women	O
+.	O
+
+In	O
+Dahl	O
+salt	B-Chemical
+-	O
+sensitive	O
+rats	O
+(	O
+DS	O
+)	O
+,	O
+high	O
+-	O
+salt	B-Chemical
+(	O
+HS	O
+)	O
+diet	O
+increases	O
+BP	O
+more	O
+in	O
+males	O
+than	O
+females	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+systemic	O
+renin	O
+-	O
+angiotensin	B-Chemical
+system	O
+,	O
+which	O
+is	O
+suppressed	O
+in	O
+response	O
+to	O
+HS	O
+in	O
+male	O
+DS	O
+,	O
+intrarenal	O
+angiotensinogen	O
+expression	O
+is	O
+increased	O
+,	O
+and	O
+intrarenal	O
+levels	O
+of	O
+ANG	O
+II	O
+are	O
+not	O
+suppressed	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+hypothesis	O
+was	O
+tested	O
+that	O
+there	O
+is	O
+a	O
+sexual	O
+dimorphism	O
+in	O
+HS	O
+-	O
+induced	O
+upregulation	O
+of	O
+intrarenal	O
+angiotensinogen	O
+mediated	O
+by	O
+testosterone	B-Chemical
+that	O
+also	O
+causes	O
+increases	O
+in	O
+BP	O
+and	O
+renal	B-Disease
+injury	I-Disease
+.	O
+
+On	O
+a	O
+low	O
+-	O
+salt	B-Chemical
+(	O
+LS	O
+)	O
+diet	O
+,	O
+male	O
+DS	O
+had	O
+higher	O
+levels	O
+of	O
+intrarenal	O
+angiotensinogen	O
+mRNA	O
+than	O
+females	O
+.	O
+
+HS	O
+diet	O
+for	O
+4	O
+wk	O
+increased	O
+renal	O
+cortical	O
+angiotensinogen	O
+mRNA	O
+and	O
+protein	O
+only	O
+in	O
+male	O
+DS	O
+,	O
+which	O
+was	O
+prevented	O
+by	O
+castration	O
+.	O
+
+Ovariectomy	O
+of	O
+female	O
+DS	O
+had	O
+no	O
+effect	O
+on	O
+intrarenal	O
+angiotensinogen	O
+expression	O
+on	O
+either	O
+diet	O
+.	O
+
+Radiotelemetric	O
+BP	O
+was	O
+similar	O
+between	O
+males	O
+and	O
+castrated	O
+rats	O
+on	O
+LS	O
+diet	O
+.	O
+
+HS	O
+diet	O
+for	O
+4	O
+wk	O
+caused	O
+a	O
+progressive	O
+increase	O
+in	O
+BP	O
+,	O
+protein	O
+and	O
+albumin	O
+excretion	O
+,	O
+and	O
+glomerular	B-Disease
+sclerosis	I-Disease
+in	O
+male	O
+DS	O
+rats	O
+,	O
+which	O
+were	O
+attenuated	O
+by	O
+castration	O
+.	O
+
+Testosterone	B-Chemical
+replacement	O
+in	O
+castrated	O
+DS	O
+rats	O
+increased	O
+BP	O
+,	O
+renal	B-Disease
+injury	I-Disease
+,	O
+and	O
+upregulation	O
+of	O
+renal	O
+angiotensinogen	O
+associated	O
+with	O
+HS	O
+diet	O
+.	O
+
+Testosterone	B-Chemical
+contributes	O
+to	O
+the	O
+development	O
+of	O
+hypertension	B-Disease
+and	O
+renal	B-Disease
+injury	I-Disease
+in	O
+male	O
+DS	O
+rats	O
+on	O
+HS	O
+diet	O
+possibly	O
+through	O
+upregulation	O
+of	O
+the	O
+intrarenal	O
+renin	O
+-	O
+angiotensin	B-Chemical
+system	O
+.	O
+
+Explicit	O
+episodic	O
+memory	O
+for	O
+sensory	O
+-	O
+discriminative	O
+components	O
+of	O
+capsaicin	B-Chemical
+-	O
+induced	O
+pain	B-Disease
+:	O
+immediate	O
+and	O
+delayed	O
+ratings	O
+.	O
+
+Pain	B-Disease
+memory	O
+is	O
+thought	O
+to	O
+affect	O
+future	O
+pain	B-Disease
+sensitivity	O
+and	O
+thus	O
+contribute	O
+to	O
+clinical	O
+pain	B-Disease
+conditions	O
+.	O
+
+Systematic	O
+investigations	O
+of	O
+the	O
+human	O
+capacity	O
+to	O
+remember	O
+sensory	O
+features	O
+of	O
+experimental	O
+pain	B-Disease
+are	O
+sparse	O
+.	O
+
+In	O
+order	O
+to	O
+address	O
+long	O
+-	O
+term	O
+pain	B-Disease
+memory	O
+,	O
+nine	O
+healthy	O
+male	O
+volunteers	O
+received	O
+intradermal	O
+injections	O
+of	O
+three	O
+doses	O
+of	O
+capsaicin	B-Chemical
+(	O
+0	O
+.	O
+05	O
+,	O
+1	O
+and	O
+20	O
+microg	O
+,	O
+separated	O
+by	O
+15	O
+min	O
+breaks	O
+)	O
+,	O
+each	O
+given	O
+three	O
+times	O
+in	O
+a	O
+balanced	O
+design	O
+across	O
+three	O
+sessions	O
+at	O
+one	O
+week	O
+intervals	O
+.	O
+
+Pain	B-Disease
+rating	O
+was	O
+performed	O
+using	O
+a	O
+computerized	O
+visual	O
+analogue	O
+scale	O
+(	O
+0	O
+-	O
+100	O
+)	O
+digitized	O
+at	O
+1	O
+/	O
+s	O
+,	O
+either	O
+immediately	O
+online	O
+or	O
+one	O
+hour	O
+or	O
+one	O
+day	O
+after	O
+injection	O
+.	O
+
+Subjects	O
+also	O
+recalled	O
+their	O
+pains	B-Disease
+one	O
+week	O
+later	O
+.	O
+
+Capsaicin	B-Chemical
+injection	O
+reliably	O
+induced	O
+a	O
+dose	O
+-	O
+dependent	O
+flare	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+without	O
+any	O
+difference	O
+within	O
+or	O
+across	O
+sessions	O
+.	O
+
+The	O
+strong	O
+burning	O
+pain	B-Disease
+decayed	O
+exponentially	O
+within	O
+a	O
+few	O
+minutes	O
+.	O
+
+Subjects	O
+were	O
+able	O
+to	O
+reliably	O
+discriminate	O
+pain	B-Disease
+magnitude	O
+and	O
+duration	O
+across	O
+capsaicin	B-Chemical
+doses	O
+(	O
+both	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+regardless	O
+of	O
+whether	O
+first	O
+-	O
+time	O
+ratings	O
+were	O
+requested	O
+immediately	O
+,	O
+after	O
+one	O
+hour	O
+or	O
+after	O
+one	O
+day	O
+.	O
+
+Pain	B-Disease
+recall	O
+after	O
+one	O
+week	O
+was	O
+similarly	O
+precise	O
+(	O
+magnitude	O
+:	O
+p	O
+<	O
+0	O
+.	O
+01	O
+,	O
+duration	O
+:	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Correlation	O
+with	O
+rating	O
+recall	O
+after	O
+one	O
+week	O
+was	O
+best	O
+when	O
+first	O
+-	O
+time	O
+ratings	O
+were	O
+requested	O
+as	O
+late	O
+as	O
+one	O
+day	O
+after	O
+injection	O
+(	O
+R	O
+(	O
+2	O
+)	O
+=	O
+0	O
+.	O
+79	O
+)	O
+indicating	O
+that	O
+both	O
+rating	O
+retrievals	O
+utilized	O
+similar	O
+memory	O
+traces	O
+.	O
+
+These	O
+results	O
+indicate	O
+a	O
+reliable	O
+memory	O
+for	O
+magnitude	O
+and	O
+duration	O
+of	O
+experimentally	O
+induced	O
+pain	B-Disease
+.	O
+
+The	O
+data	O
+further	O
+suggest	O
+that	O
+the	O
+consolidation	O
+of	O
+this	O
+memory	O
+is	O
+an	O
+important	O
+interim	O
+stage	O
+,	O
+and	O
+may	O
+take	O
+up	O
+to	O
+one	O
+day	O
+.	O
+
+Severe	O
+and	O
+long	O
+lasting	O
+cholestasis	B-Disease
+after	O
+high	O
+-	O
+dose	O
+co	B-Chemical
+-	I-Chemical
+trimoxazole	I-Chemical
+treatment	O
+for	O
+Pneumocystis	B-Disease
+pneumonia	I-Disease
+in	O
+HIV	B-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+-	O
+-	O
+a	O
+report	O
+of	O
+two	O
+cases	O
+.	O
+
+Pneumocystis	B-Disease
+pneumonia	I-Disease
+(	O
+PCP	B-Disease
+)	O
+,	O
+a	O
+common	O
+opportunistic	B-Disease
+infection	I-Disease
+in	O
+HIV	B-Disease
+-	I-Disease
+infected	I-Disease
+individuals	O
+,	O
+is	O
+generally	O
+treated	O
+with	O
+high	O
+doses	O
+of	O
+co	B-Chemical
+-	I-Chemical
+trimoxazole	I-Chemical
+.	O
+
+However	O
+,	O
+treatment	O
+is	O
+often	O
+limited	O
+by	O
+adverse	O
+effects	O
+.	O
+
+Here	O
+,	O
+we	O
+report	O
+two	O
+cases	O
+of	O
+severely	O
+immunocompromised	O
+HIV	B-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+who	O
+developed	O
+severe	O
+intrahepatic	B-Disease
+cholestasis	I-Disease
+,	O
+and	O
+in	O
+one	O
+patient	O
+lesions	O
+mimicking	O
+liver	B-Disease
+abscess	I-Disease
+formation	O
+on	O
+radiologic	O
+exams	O
+,	O
+during	O
+co	B-Chemical
+-	I-Chemical
+trimoxazole	I-Chemical
+treatment	O
+for	O
+PCP	B-Disease
+.	O
+
+Whereas	O
+patient	O
+1	O
+showed	O
+lesions	O
+of	O
+up	O
+to	O
+1	O
+cm	O
+readily	O
+detectable	O
+on	O
+magnetic	O
+resonance	O
+imaging	O
+under	O
+prolonged	O
+co	B-Chemical
+-	I-Chemical
+trimoxazole	I-Chemical
+treatment	O
+,	O
+therapy	O
+of	O
+patient	O
+2	O
+was	O
+switched	O
+early	O
+.	O
+
+Bradykinin	B-Chemical
+receptors	O
+antagonists	O
+and	O
+nitric	B-Chemical
+oxide	I-Chemical
+synthase	O
+inhibitors	O
+in	O
+vincristine	B-Chemical
+and	O
+streptozotocin	B-Chemical
+induced	O
+hyperalgesia	B-Disease
+in	O
+chemotherapy	O
+and	O
+diabetic	B-Disease
+neuropathy	I-Disease
+rat	O
+model	O
+.	O
+
+PURPOSE	O
+:	O
+The	O
+influence	O
+of	O
+an	O
+irreversible	O
+inhibitor	O
+of	O
+constitutive	O
+NO	B-Chemical
+synthase	O
+(	O
+L	O
+-	O
+NOArg	O
+;	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+ip	O
+)	O
+,	O
+a	O
+relatively	O
+selective	O
+inhibitor	O
+of	O
+inducible	O
+NO	B-Chemical
+synthase	O
+(	O
+L	O
+-	O
+NIL	O
+;	O
+1	O
+.	O
+0	O
+mg	O
+/	O
+kg	O
+ip	O
+)	O
+and	O
+a	O
+relatively	O
+specific	O
+inhibitor	O
+of	O
+neuronal	O
+NO	B-Chemical
+synthase	O
+(	O
+7	O
+-	O
+NI	O
+;	O
+0	O
+.	O
+1	O
+mg	O
+/	O
+kg	O
+ip	O
+)	O
+,	O
+on	O
+antihyperalgesic	O
+action	O
+of	O
+selective	O
+antagonists	O
+of	O
+B2	O
+and	O
+B1	O
+receptors	O
+:	O
+D	O
+-	O
+Arg	O
+-	O
+[	O
+Hyp3	O
+,	O
+Thi5	O
+,	O
+D	O
+-	O
+Tic7	O
+,	O
+Oic8	O
+]	O
+bradykinin	B-Chemical
+(	O
+HOE	B-Chemical
+140	I-Chemical
+;	O
+70	O
+nmol	O
+/	O
+kg	O
+ip	O
+)	O
+or	O
+des	B-Chemical
+Arg10	I-Chemical
+HOE	I-Chemical
+140	I-Chemical
+(	O
+70	O
+nmol	O
+/	O
+kg	O
+ip	O
+)	O
+respectively	O
+,	O
+in	O
+model	O
+of	O
+diabetic	B-Disease
+(	I-Disease
+streptozotocin	I-Disease
+-	I-Disease
+induced	I-Disease
+)	I-Disease
+and	I-Disease
+toxic	I-Disease
+(	I-Disease
+vincristine	I-Disease
+-	I-Disease
+induced	I-Disease
+)	I-Disease
+neuropathy	I-Disease
+was	O
+investigated	O
+.	O
+
+METHODS	O
+:	O
+The	O
+changes	O
+in	O
+pain	B-Disease
+thresholds	O
+were	O
+determined	O
+using	O
+mechanical	O
+stimuli	O
+-	O
+-	O
+the	O
+modification	O
+of	O
+the	O
+classic	O
+paw	O
+withdrawal	O
+test	O
+described	O
+by	O
+Randall	O
+-	O
+Selitto	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+results	O
+of	O
+this	O
+paper	O
+confirm	O
+that	O
+inhibition	O
+of	O
+bradykinin	B-Chemical
+receptors	O
+and	O
+inducible	O
+NO	B-Chemical
+synthase	O
+but	O
+not	O
+neuronal	O
+NO	B-Chemical
+synthase	O
+activity	O
+reduces	O
+diabetic	B-Disease
+hyperalgesia	I-Disease
+.	O
+
+Pretreatment	O
+with	O
+L	O
+-	O
+NOArg	O
+and	O
+L	O
+-	O
+NIL	O
+but	O
+not	O
+7	O
+-	O
+NI	O
+,	O
+significantly	O
+increases	O
+antihyperalgesic	O
+activity	O
+both	O
+HOE	B-Chemical
+140	I-Chemical
+and	O
+des	B-Chemical
+Arg10	I-Chemical
+HOE	I-Chemical
+140	I-Chemical
+.	O
+
+It	O
+was	O
+also	O
+shown	O
+that	O
+both	O
+products	O
+of	O
+inducible	O
+NO	B-Chemical
+synthase	O
+and	O
+neuronal	O
+NO	B-Chemical
+synthase	O
+activation	O
+as	O
+well	O
+as	O
+bradykinin	B-Chemical
+are	O
+involved	O
+in	O
+hyperalgesia	B-Disease
+produced	O
+by	O
+vincristine	B-Chemical
+.	O
+
+Moreover	O
+,	O
+L	O
+-	O
+NOArg	O
+and	O
+7	O
+-	O
+NI	O
+but	O
+not	O
+L	O
+-	O
+NIL	O
+intensify	O
+antihyperalgesic	O
+activity	O
+of	O
+HOE	B-Chemical
+140	I-Chemical
+or	O
+des	B-Chemical
+-	I-Chemical
+Arg10HOE	I-Chemical
+140	I-Chemical
+in	O
+toxic	B-Disease
+neuropathy	I-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+Results	O
+of	O
+these	O
+studies	O
+suggest	O
+that	O
+B1	O
+and	O
+B2	O
+receptors	O
+are	O
+engaged	O
+in	O
+transmission	O
+of	O
+nociceptive	O
+stimuli	O
+in	O
+both	O
+diabetic	B-Disease
+and	I-Disease
+toxic	I-Disease
+neuropathy	I-Disease
+.	O
+
+In	O
+streptozotocin	B-Chemical
+-	O
+induced	O
+hyperalgesia	B-Disease
+,	O
+inducible	O
+NO	B-Chemical
+synthase	O
+participates	O
+in	O
+pronociceptive	O
+activity	O
+of	O
+bradykinin	B-Chemical
+,	O
+whereas	O
+in	O
+vincristine	B-Chemical
+-	O
+induced	O
+hyperalgesia	B-Disease
+bradykinin	B-Chemical
+seemed	O
+to	O
+activate	O
+neuronal	O
+NO	B-Chemical
+synthase	O
+pathway	O
+.	O
+
+Therefore	O
+,	O
+concomitant	O
+administration	O
+of	O
+small	O
+doses	O
+of	O
+bradykinin	B-Chemical
+receptor	O
+antagonists	O
+and	O
+NO	B-Chemical
+synthase	O
+inhibitors	O
+can	O
+be	O
+effective	O
+in	O
+alleviation	O
+of	O
+neuropathic	B-Disease
+pain	I-Disease
+,	O
+even	O
+in	O
+hospital	O
+care	O
+.	O
+
+Confusion	B-Disease
+,	O
+a	O
+rather	O
+serious	O
+adverse	O
+drug	O
+reaction	O
+with	O
+valproic	B-Chemical
+acid	I-Chemical
+:	O
+a	O
+review	O
+of	O
+the	O
+French	O
+Pharmacovigilance	O
+database	O
+.	O
+
+INTRODUCTION	O
+:	O
+Confusion	B-Disease
+is	O
+an	O
+adverse	O
+drug	O
+reaction	O
+frequently	O
+observed	O
+with	O
+valproic	B-Chemical
+acid	I-Chemical
+.	O
+
+Some	O
+case	O
+reports	O
+are	O
+published	O
+in	O
+the	O
+literature	O
+but	O
+no	O
+systematic	O
+study	O
+from	O
+a	O
+sample	O
+of	O
+patients	O
+has	O
+been	O
+published	O
+.	O
+
+We	O
+performed	O
+this	O
+study	O
+in	O
+order	O
+to	O
+describe	O
+the	O
+main	O
+characteristics	O
+of	O
+this	O
+adverse	O
+drug	O
+reaction	O
+.	O
+
+METHODS	O
+:	O
+Using	O
+the	O
+French	O
+Pharmacovigilance	O
+database	O
+,	O
+we	O
+selected	O
+the	O
+cases	O
+of	O
+confusion	B-Disease
+reported	O
+since	O
+1985	O
+with	O
+valproic	B-Chemical
+acid	I-Chemical
+.	O
+
+RESULTS	O
+:	O
+272	O
+cases	O
+of	O
+confusion	B-Disease
+were	O
+reported	O
+with	O
+valproic	B-Chemical
+acid	I-Chemical
+:	O
+153	O
+women	O
+and	O
+119	O
+men	O
+.	O
+
+Confusion	B-Disease
+mostly	O
+occurred	O
+during	O
+the	O
+two	O
+first	O
+weeks	O
+following	O
+valproic	B-Chemical
+acid	I-Chemical
+exposure	O
+(	O
+39	O
+.	O
+7	O
+%	O
+)	O
+.	O
+
+It	O
+was	O
+"	O
+serious	O
+"	O
+for	O
+almost	O
+2	O
+/	O
+3	O
+of	O
+the	O
+patients	O
+(	O
+62	O
+.	O
+5	O
+%	O
+)	O
+and	O
+its	O
+outcome	O
+favourable	O
+in	O
+most	O
+of	O
+the	O
+cases	O
+(	O
+82	O
+%	O
+)	O
+.	O
+
+The	O
+occurrence	O
+of	O
+this	O
+ADR	O
+was	O
+more	O
+frequent	O
+in	O
+patients	O
+aged	O
+between	O
+61	O
+and	O
+80	O
+years	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+work	O
+shows	O
+that	O
+confusion	B-Disease
+with	O
+valproic	B-Chemical
+acid	I-Chemical
+is	O
+a	O
+serious	O
+,	O
+rather	O
+frequent	O
+but	O
+reversible	O
+adverse	O
+drug	O
+reaction	O
+.	O
+
+It	O
+occurs	O
+especially	O
+in	O
+older	O
+patients	O
+and	O
+during	O
+the	O
+first	O
+two	O
+weeks	O
+of	O
+treatment	O
+.	O
+
+Reversible	O
+inferior	B-Disease
+colliculus	I-Disease
+lesion	I-Disease
+in	O
+metronidazole	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+:	O
+magnetic	O
+resonance	O
+findings	O
+on	O
+diffusion	O
+-	O
+weighted	O
+and	O
+fluid	O
+attenuated	O
+inversion	O
+recovery	O
+imaging	O
+.	O
+
+OBJECTIVE	O
+:	O
+This	O
+is	O
+to	O
+present	O
+reversible	O
+inferior	B-Disease
+colliculus	I-Disease
+lesions	I-Disease
+in	O
+metronidazole	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+,	O
+to	O
+focus	O
+on	O
+the	O
+diffusion	O
+-	O
+weighted	O
+imaging	O
+(	O
+DWI	O
+)	O
+and	O
+fluid	O
+attenuated	O
+inversion	O
+recovery	O
+(	O
+FLAIR	O
+)	O
+imaging	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+:	O
+From	O
+November	O
+2005	O
+to	O
+September	O
+2007	O
+,	O
+8	O
+patients	O
+(	O
+5	O
+men	O
+and	O
+3	O
+women	O
+)	O
+were	O
+diagnosed	O
+as	O
+having	O
+metronidazole	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+(	O
+age	O
+range	O
+;	O
+43	O
+-	O
+78	O
+years	O
+)	O
+.	O
+
+They	O
+had	O
+been	O
+taking	O
+metronidazole	B-Chemical
+(	O
+total	O
+dosage	O
+,	O
+45	O
+-	O
+120	O
+g	O
+;	O
+duration	O
+,	O
+30	O
+days	O
+to	O
+2	O
+months	O
+)	O
+to	O
+treat	O
+the	O
+infection	B-Disease
+in	O
+various	O
+organs	O
+.	O
+
+Initial	O
+brain	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+MRI	O
+)	O
+were	O
+obtained	O
+after	O
+the	O
+hospitalization	O
+,	O
+including	O
+DWI	O
+(	O
+8	O
+/	O
+8	O
+)	O
+,	O
+apparent	O
+diffusion	O
+coefficient	O
+(	O
+ADC	O
+)	O
+map	O
+(	O
+4	O
+/	O
+8	O
+)	O
+,	O
+FLAIR	O
+(	O
+7	O
+/	O
+8	O
+)	O
+,	O
+and	O
+T2	O
+-	O
+weighted	O
+image	O
+(	O
+8	O
+/	O
+8	O
+)	O
+.	O
+
+Follow	O
+-	O
+up	O
+MRIs	O
+were	O
+performed	O
+on	O
+5	O
+patients	O
+from	O
+third	O
+to	O
+14th	O
+days	O
+after	O
+discontinuation	O
+of	O
+metronidazole	B-Chemical
+administration	O
+.	O
+
+Findings	O
+of	O
+initial	O
+and	O
+follow	O
+-	O
+up	O
+MRIs	O
+were	O
+retrospectively	O
+evaluated	O
+by	O
+2	O
+neuroradiologists	O
+by	O
+consensus	O
+,	O
+to	O
+analyze	O
+the	O
+presence	O
+of	O
+abnormal	O
+signal	O
+intensities	O
+,	O
+their	O
+locations	O
+,	O
+and	O
+signal	O
+changes	O
+on	O
+follow	O
+-	O
+up	O
+images	O
+.	O
+
+RESULTS	O
+:	O
+Initial	O
+MRIs	O
+showed	O
+abnormal	O
+high	O
+signal	O
+intensities	O
+on	O
+DWI	O
+and	O
+FLAIR	O
+(	O
+or	O
+T2	O
+-	O
+weighted	O
+image	O
+)	O
+at	O
+the	O
+dentate	O
+nucleus	O
+(	O
+8	O
+/	O
+8	O
+)	O
+,	O
+inferior	O
+colliculus	O
+(	O
+6	O
+/	O
+8	O
+)	O
+,	O
+corpus	O
+callosum	O
+(	O
+2	O
+/	O
+8	O
+)	O
+,	O
+pons	O
+(	O
+2	O
+/	O
+8	O
+)	O
+,	O
+medulla	O
+(	O
+1	O
+/	O
+8	O
+)	O
+,	O
+and	O
+bilateral	O
+cerebral	O
+white	O
+matter	O
+(	O
+1	O
+/	O
+8	O
+)	O
+.	O
+
+High	O
+-	O
+signal	O
+intensity	O
+lesions	O
+on	O
+DWI	O
+tended	O
+to	O
+show	O
+low	O
+signal	O
+intensity	O
+on	O
+ADC	O
+map	O
+(	O
+3	O
+/	O
+4	O
+)	O
+,	O
+but	O
+in	O
+one	O
+patient	O
+,	O
+high	O
+signal	O
+intensity	O
+was	O
+shown	O
+at	O
+bilateral	O
+dentate	O
+nuclei	O
+on	O
+not	O
+only	O
+DWI	O
+but	O
+also	O
+ADC	O
+map	O
+.	O
+
+All	O
+the	O
+lesions	O
+in	O
+dentate	O
+,	O
+inferior	O
+colliculus	O
+,	O
+pons	O
+,	O
+and	O
+medullas	O
+had	O
+been	O
+resolved	O
+completely	O
+on	O
+follow	O
+-	O
+up	O
+MRIs	O
+in	O
+5	O
+patients	O
+,	O
+but	O
+in	O
+1	O
+patient	O
+of	O
+them	O
+,	O
+corpus	O
+callosal	B-Disease
+lesion	I-Disease
+persisted	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Reversible	O
+inferior	B-Disease
+colliculus	I-Disease
+lesions	I-Disease
+could	O
+be	O
+considered	O
+as	O
+the	O
+characteristic	O
+for	O
+metronidazole	B-Chemical
+-	O
+induced	O
+encephalopathy	B-Disease
+,	O
+next	O
+to	O
+the	O
+dentate	O
+nucleus	O
+involvement	O
+.	O
+
+Clinically	O
+significant	O
+proteinuria	B-Disease
+following	O
+the	O
+administration	O
+of	O
+sirolimus	B-Chemical
+to	O
+renal	O
+transplant	O
+recipients	O
+.	O
+
+BACKGROUND	O
+:	O
+Sirolimus	B-Chemical
+is	O
+the	O
+latest	O
+immunosuppressive	O
+agent	O
+used	O
+to	O
+prevent	O
+rejection	O
+,	O
+and	O
+may	O
+have	O
+less	O
+nephrotoxicity	B-Disease
+than	O
+calcineurin	O
+inhibitor	O
+(	O
+CNI	O
+)	O
+-	O
+based	O
+regimens	O
+.	O
+
+To	O
+date	O
+there	O
+has	O
+been	O
+little	O
+documentation	O
+of	O
+clinically	O
+significant	O
+proteinuria	B-Disease
+linked	O
+with	O
+the	O
+use	O
+of	O
+sirolimus	B-Chemical
+.	O
+
+We	O
+have	O
+encountered	O
+several	O
+patients	O
+who	O
+developed	O
+substantial	O
+proteinuria	B-Disease
+associated	O
+with	O
+sirolimus	B-Chemical
+use	O
+.	O
+
+In	O
+each	O
+patient	O
+,	O
+the	O
+close	O
+temporal	O
+association	O
+between	O
+the	O
+commencement	O
+of	O
+sirolimus	B-Chemical
+therapy	O
+and	O
+proteinuria	B-Disease
+implicated	O
+sirolimus	B-Chemical
+as	O
+the	O
+most	O
+likely	O
+etiology	O
+of	O
+the	O
+proteinuria	B-Disease
+.	O
+
+METHODS	O
+:	O
+We	O
+analyzed	O
+the	O
+clinical	O
+and	O
+laboratory	O
+information	O
+available	O
+for	O
+all	O
+119	O
+patients	O
+transplanted	O
+at	O
+the	O
+Washington	O
+Hospital	O
+Center	O
+between	O
+1999	O
+-	O
+2003	O
+for	O
+whom	O
+sirolimus	B-Chemical
+was	O
+a	O
+component	O
+of	O
+their	O
+immunosuppressant	O
+regimen	O
+.	O
+
+In	O
+these	O
+patients	O
+,	O
+the	O
+magnitude	O
+of	O
+proteinuria	B-Disease
+was	O
+assessed	O
+on	O
+morning	O
+urine	O
+samples	O
+by	O
+turbidometric	O
+measurement	O
+or	O
+random	O
+urine	O
+protein	O
+:	O
+creatinine	B-Chemical
+ratios	O
+,	O
+an	O
+estimate	O
+of	O
+grams	O
+of	O
+proteinuria	B-Disease
+/	O
+day	O
+.	O
+
+Laboratory	O
+results	O
+were	O
+compared	O
+between	O
+prior	O
+,	O
+during	O
+and	O
+following	O
+sirolimus	B-Chemical
+use	O
+.	O
+
+RESULTS	O
+:	O
+Twenty	O
+-	O
+eight	O
+patients	O
+(	O
+24	O
+%	O
+)	O
+developed	O
+increased	O
+proteinuria	B-Disease
+from	O
+baseline	O
+during	O
+their	O
+post	O
+-	O
+transplantation	O
+course	O
+.	O
+
+In	O
+21	O
+patients	O
+an	O
+alternative	O
+cause	O
+of	O
+proteinuria	B-Disease
+was	O
+either	O
+obvious	O
+or	O
+insufficient	O
+data	O
+was	O
+available	O
+to	O
+be	O
+conclusive	O
+.	O
+
+In	O
+7	O
+of	O
+the	O
+28	O
+patients	O
+there	O
+was	O
+a	O
+striking	O
+temporal	O
+association	O
+between	O
+the	O
+initiation	O
+of	O
+sirolimus	B-Chemical
+and	O
+the	O
+development	O
+of	O
+nephrotic	B-Disease
+-	O
+range	O
+proteinuria	B-Disease
+.	O
+
+Proteinuria	B-Disease
+correlated	O
+most	O
+strongly	O
+with	O
+sirolimus	B-Chemical
+therapy	O
+when	O
+compared	O
+to	O
+other	O
+demographic	O
+and	O
+clinical	O
+variables	O
+.	O
+
+In	O
+most	O
+patients	O
+,	O
+discontinuation	O
+of	O
+sirolimus	B-Chemical
+resulted	O
+in	O
+a	O
+decrease	O
+,	O
+but	O
+not	O
+resolution	O
+,	O
+of	O
+proteinuria	B-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+Sirolimus	B-Chemical
+induces	O
+or	O
+aggravates	O
+pre	O
+-	O
+existing	O
+proteinuria	B-Disease
+in	O
+an	O
+unpredictable	O
+subset	O
+of	O
+renal	O
+allograft	O
+recipients	O
+.	O
+
+Proteinuria	B-Disease
+may	O
+improve	O
+,	O
+but	O
+does	O
+not	O
+resolve	O
+,	O
+when	O
+sirolimus	B-Chemical
+is	O
+withdrawn	O
+.	O
+
+Components	O
+of	O
+lemon	O
+essential	O
+oil	O
+attenuate	O
+dementia	B-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+.	O
+
+The	O
+anti	O
+-	O
+dementia	B-Disease
+effects	O
+of	O
+s	B-Chemical
+-	I-Chemical
+limonene	I-Chemical
+and	O
+s	B-Chemical
+-	I-Chemical
+perillyl	I-Chemical
+alcohol	I-Chemical
+were	O
+observed	O
+using	O
+the	O
+passive	O
+avoidance	O
+test	O
+(	O
+PA	O
+)	O
+and	O
+the	O
+open	O
+field	O
+habituation	O
+test	O
+(	O
+OFH	O
+)	O
+.	O
+
+These	O
+lemon	O
+essential	O
+oils	O
+showed	O
+strong	O
+ability	O
+to	O
+improve	O
+memory	B-Disease
+impaired	I-Disease
+by	O
+scopolamine	B-Chemical
+;	O
+however	O
+,	O
+s	B-Chemical
+-	I-Chemical
+perillyl	I-Chemical
+alcohol	I-Chemical
+relieved	O
+the	O
+deficit	B-Disease
+of	I-Disease
+associative	I-Disease
+memory	I-Disease
+in	O
+PA	O
+only	O
+,	O
+and	O
+did	O
+not	O
+improve	O
+non	O
+-	O
+associative	O
+memory	O
+significantly	O
+in	O
+OFH	O
+.	O
+
+Analysis	O
+of	O
+neurotransmitter	O
+concentration	O
+in	O
+some	O
+brain	O
+regions	O
+on	O
+the	O
+test	O
+day	O
+showed	O
+that	O
+dopamine	B-Chemical
+concentration	O
+of	O
+the	O
+vehicle	O
+/	O
+scopolamine	B-Chemical
+group	O
+was	O
+significantly	O
+lower	O
+than	O
+that	O
+of	O
+the	O
+vehicle	O
+/	O
+vehicle	O
+group	O
+,	O
+but	O
+this	O
+phenomenon	O
+was	O
+reversed	O
+when	O
+s	B-Chemical
+-	I-Chemical
+limonene	I-Chemical
+or	O
+s	B-Chemical
+-	I-Chemical
+perillyl	I-Chemical
+alcohol	I-Chemical
+were	O
+administered	O
+before	O
+the	O
+injection	O
+of	O
+scopolamine	B-Chemical
+.	O
+
+Simultaneously	O
+,	O
+we	O
+found	O
+that	O
+these	O
+two	O
+lemon	O
+essential	O
+oil	O
+components	O
+could	O
+inhibit	O
+acetylcholinesterase	O
+activity	O
+in	O
+vitro	O
+using	O
+the	O
+Ellman	O
+method	O
+.	O
+
+Attentional	O
+modulation	O
+of	O
+perceived	O
+pain	B-Disease
+intensity	O
+in	O
+capsaicin	B-Chemical
+-	O
+induced	O
+secondary	O
+hyperalgesia	B-Disease
+.	O
+
+Perceived	O
+pain	B-Disease
+intensity	O
+is	O
+modulated	O
+by	O
+attention	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+not	O
+known	O
+that	O
+how	O
+pain	B-Disease
+intensity	O
+ratings	O
+are	O
+affected	O
+by	O
+attention	O
+in	O
+capsaicin	B-Chemical
+-	O
+induced	O
+secondary	O
+hyperalgesia	B-Disease
+.	O
+
+Here	O
+we	O
+show	O
+that	O
+perceived	O
+pain	B-Disease
+intensity	O
+in	O
+secondary	O
+hyperalgesia	B-Disease
+is	O
+decreased	O
+when	O
+attention	O
+is	O
+distracted	O
+away	O
+from	O
+the	O
+painful	O
+pinprick	O
+stimulus	O
+with	O
+a	O
+visual	O
+task	O
+.	O
+
+Furthermore	O
+,	O
+it	O
+was	O
+found	O
+that	O
+the	O
+magnitude	O
+of	O
+attentional	O
+modulation	O
+in	O
+secondary	O
+hyperalgesia	B-Disease
+is	O
+very	O
+similar	O
+to	O
+that	O
+of	O
+capsaicin	B-Chemical
+-	O
+untreated	O
+,	O
+control	O
+condition	O
+.	O
+
+Our	O
+findings	O
+,	O
+showing	O
+no	O
+interaction	O
+between	O
+capsaicin	B-Chemical
+treatment	O
+and	O
+attentional	O
+modulation	O
+suggest	O
+that	O
+capsaicin	B-Chemical
+-	O
+induced	O
+secondary	O
+hyperalgesia	B-Disease
+and	O
+attention	O
+might	O
+affect	O
+mechanical	O
+pain	B-Disease
+through	O
+independent	O
+mechanisms	O
+.	O
+
+Cardioprotective	O
+effect	O
+of	O
+salvianolic	B-Chemical
+acid	I-Chemical
+A	I-Chemical
+on	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+evaluate	O
+the	O
+cardioprotective	O
+potential	O
+of	O
+salvianolic	B-Chemical
+acid	I-Chemical
+A	I-Chemical
+on	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+rats	O
+.	O
+
+Hemodynamic	O
+parameters	O
+and	O
+lead	O
+II	O
+electrocardiograph	O
+were	O
+monitored	O
+and	O
+recorded	O
+continuously	O
+.	O
+
+Cardiac	O
+marker	O
+enzymes	O
+and	O
+antioxidative	O
+parameters	O
+in	O
+serum	O
+and	O
+heart	O
+tissues	O
+were	O
+measured	O
+.	O
+
+Assay	O
+for	O
+mitochondrial	O
+respiratory	O
+function	O
+and	O
+histopathological	O
+examination	O
+of	O
+heart	O
+tissues	O
+were	O
+performed	O
+.	O
+
+Isoproterenol	B-Chemical
+-	O
+treated	O
+rats	O
+showed	O
+significant	O
+increases	O
+in	O
+the	O
+levels	O
+of	O
+lactate	B-Chemical
+dehydrogenase	O
+,	O
+aspartate	B-Chemical
+transaminase	O
+,	O
+creatine	B-Chemical
+kinase	O
+and	O
+malondialdehyde	B-Chemical
+and	O
+significant	O
+decreases	O
+in	O
+the	O
+activities	O
+of	O
+superoxide	B-Chemical
+dismutase	O
+,	O
+catalase	O
+and	O
+glutathione	B-Chemical
+peroxidase	O
+in	O
+serum	O
+and	O
+heart	O
+.	O
+
+These	O
+rats	O
+also	O
+showed	O
+declines	O
+in	O
+left	O
+ventricular	O
+systolic	O
+pressure	O
+,	O
+maximum	O
+and	O
+minimum	O
+rate	O
+of	O
+developed	O
+left	O
+ventricular	O
+pressure	O
+,	O
+and	O
+elevation	O
+of	O
+left	O
+ventricular	O
+end	O
+-	O
+diastolic	O
+pressure	O
+and	O
+ST	O
+-	O
+segment	O
+.	O
+
+In	O
+addition	O
+,	O
+mitochondrial	O
+respiratory	B-Disease
+dysfunction	I-Disease
+characterized	O
+by	O
+decreased	O
+respiratory	O
+control	O
+ratio	O
+and	O
+ADP	B-Chemical
+/	O
+O	O
+was	O
+observed	O
+in	O
+isoproterenol	B-Chemical
+-	O
+treated	O
+rats	O
+.	O
+
+Administration	O
+of	O
+salvianolic	B-Chemical
+acid	I-Chemical
+A	I-Chemical
+for	O
+a	O
+period	O
+of	O
+8	O
+days	O
+significantly	O
+attenuated	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+dysfunction	I-Disease
+and	O
+myocardial	B-Disease
+injury	I-Disease
+and	O
+improved	O
+mitochondrial	O
+respiratory	O
+function	O
+.	O
+
+The	O
+protective	O
+role	O
+of	O
+salvianolic	B-Chemical
+acid	I-Chemical
+A	I-Chemical
+against	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+damage	I-Disease
+was	O
+further	O
+confirmed	O
+by	O
+histopathological	O
+examination	O
+.	O
+
+The	O
+results	O
+of	O
+our	O
+study	O
+suggest	O
+that	O
+salvianolic	B-Chemical
+acid	I-Chemical
+A	I-Chemical
+possessing	O
+antioxidant	O
+activity	O
+has	O
+a	O
+significant	O
+protective	O
+effect	O
+against	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+Long	O
+-	O
+term	O
+glutamate	B-Chemical
+supplementation	O
+failed	O
+to	O
+protect	O
+against	O
+peripheral	B-Disease
+neurotoxicity	I-Disease
+of	O
+paclitaxel	B-Chemical
+.	O
+
+Toxic	O
+peripheral	B-Disease
+neuropathy	I-Disease
+is	O
+still	O
+a	O
+significant	O
+limiting	O
+factor	O
+for	O
+chemotherapy	O
+with	O
+paclitaxel	B-Chemical
+(	O
+PAC	B-Chemical
+)	O
+,	O
+although	O
+glutamate	B-Chemical
+and	O
+its	O
+closely	O
+related	O
+amino	B-Chemical
+acid	I-Chemical
+glutamine	B-Chemical
+were	O
+claimed	O
+to	O
+ameliorate	O
+PAC	B-Chemical
+neurotoxicity	B-Disease
+.	O
+
+This	O
+pilot	O
+trial	O
+aimed	O
+to	O
+evaluate	O
+the	O
+role	O
+of	O
+glutamate	B-Chemical
+supplementation	O
+for	O
+preventing	O
+PAC	B-Chemical
+-	O
+induced	O
+peripheral	B-Disease
+neuropathy	I-Disease
+in	O
+a	O
+randomized	O
+,	O
+placebo	O
+-	O
+controlled	O
+,	O
+double	O
+-	O
+blinded	O
+clinical	O
+and	O
+electro	O
+-	O
+diagnostic	O
+study	O
+.	O
+
+Forty	O
+-	O
+three	O
+ovarian	B-Disease
+cancer	I-Disease
+patients	O
+were	O
+available	O
+for	O
+analysis	O
+following	O
+six	O
+cycles	O
+of	O
+the	O
+same	O
+PAC	B-Chemical
+-	O
+containing	O
+regimen	O
+:	O
+23	O
+had	O
+been	O
+supplemented	O
+by	O
+glutamate	B-Chemical
+all	O
+along	O
+the	O
+treatment	O
+period	O
+,	O
+at	O
+a	O
+daily	O
+dose	O
+of	O
+three	O
+times	O
+500	O
+mg	O
+(	O
+group	O
+G	O
+)	O
+,	O
+and	O
+20	O
+had	O
+received	O
+a	O
+placebo	O
+(	O
+group	O
+P	O
+)	O
+.	O
+
+Patients	O
+were	O
+evaluated	O
+by	O
+neurological	O
+examinations	O
+,	O
+questionnaires	O
+and	O
+sensory	O
+-	O
+motor	O
+nerve	O
+conduction	O
+studies	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
+difference	O
+in	O
+the	O
+frequency	O
+of	O
+signs	O
+or	O
+symptoms	O
+between	O
+the	O
+two	O
+groups	O
+although	O
+neurotoxicity	B-Disease
+symptoms	O
+presented	O
+mostly	O
+with	O
+lower	O
+scores	O
+of	O
+severity	O
+in	O
+group	O
+G	O
+.	O
+
+However	O
+,	O
+this	O
+difference	O
+reached	O
+statistical	O
+significance	O
+only	O
+with	O
+regard	O
+to	O
+reported	O
+pain	B-Disease
+sensation	O
+(	O
+P	O
+=	O
+0	O
+.	O
+011	O
+)	O
+.	O
+
+Also	O
+the	O
+frequency	O
+of	O
+abnormal	O
+electro	O
+-	O
+diagnostic	O
+findings	O
+showed	O
+similarity	O
+between	O
+the	O
+two	O
+groups	O
+(	O
+G	O
+:	O
+7	O
+/	O
+23	O
+=	O
+30	O
+.	O
+4	O
+%	O
+;	O
+P	O
+:	O
+6	O
+/	O
+20	O
+=	O
+30	O
+%	O
+)	O
+.	O
+
+This	O
+pilot	O
+study	O
+leads	O
+to	O
+the	O
+conclusion	O
+that	O
+glutamate	B-Chemical
+supplementation	O
+at	O
+the	O
+chosen	O
+regimen	O
+fails	O
+to	O
+protect	O
+against	O
+peripheral	B-Disease
+neurotoxicity	I-Disease
+of	O
+PAC	B-Chemical
+.	O
+
+Development	O
+of	O
+ocular	B-Disease
+myasthenia	I-Disease
+during	O
+pegylated	B-Chemical
+interferon	I-Chemical
+and	O
+ribavirin	B-Chemical
+treatment	O
+for	O
+chronic	B-Disease
+hepatitis	I-Disease
+C	I-Disease
+.	O
+
+A	O
+63	O
+-	O
+year	O
+-	O
+old	O
+male	O
+experienced	O
+sudden	O
+diplopia	B-Disease
+after	O
+9	O
+weeks	O
+of	O
+administration	O
+of	O
+pegylated	B-Chemical
+interferon	I-Chemical
+(	I-Chemical
+IFN	I-Chemical
+)	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+2b	I-Chemical
+and	O
+ribavirin	B-Chemical
+for	O
+chronic	B-Disease
+hepatitis	I-Disease
+C	I-Disease
+(	O
+CHC	B-Disease
+)	O
+.	O
+
+Ophthalmologic	O
+examinations	O
+showed	O
+ptosis	B-Disease
+on	I-Disease
+the	I-Disease
+right	I-Disease
+upper	I-Disease
+lid	I-Disease
+and	O
+restricted	B-Disease
+right	I-Disease
+eye	I-Disease
+movement	I-Disease
+without	O
+any	O
+other	O
+neurological	O
+signs	O
+.	O
+
+A	O
+brain	O
+imaging	O
+study	O
+and	O
+repetitive	O
+nerve	O
+stimulation	O
+test	O
+indicated	O
+no	O
+abnormality	O
+.	O
+
+The	O
+acetylcholine	B-Chemical
+receptor	O
+antibody	O
+titer	O
+and	O
+response	O
+to	O
+acetylcholinesterase	O
+inhibitors	O
+were	O
+negative	O
+,	O
+and	O
+the	O
+results	O
+of	O
+thyroid	O
+function	O
+tests	O
+were	O
+normal	O
+.	O
+
+The	O
+patient	O
+'	O
+s	O
+ophthalmological	O
+symptoms	O
+improved	O
+rapidly	O
+3	O
+weeks	O
+after	O
+discontinuation	O
+of	O
+pegylated	B-Chemical
+IFN	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+2b	I-Chemical
+and	O
+ribavirin	B-Chemical
+.	O
+
+The	O
+ocular	B-Disease
+myasthenia	I-Disease
+associated	O
+with	O
+combination	O
+therapy	O
+of	O
+pegylated	B-Chemical
+IFN	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+2b	I-Chemical
+and	O
+ribavirin	B-Chemical
+for	O
+CHC	B-Disease
+is	O
+very	O
+rarely	O
+reported	O
+;	O
+therefore	O
+,	O
+we	O
+present	O
+this	O
+case	O
+with	O
+a	O
+review	O
+of	O
+the	O
+various	O
+eye	O
+complications	O
+of	O
+IFN	B-Chemical
+therapy	O
+.	O
+
+Learning	B-Disease
+and	I-Disease
+memory	I-Disease
+deficits	I-Disease
+in	O
+ecstasy	B-Chemical
+users	O
+and	O
+their	O
+neural	O
+correlates	O
+during	O
+a	O
+face	O
+-	O
+learning	O
+task	O
+.	O
+
+It	O
+has	O
+been	O
+consistently	O
+shown	O
+that	O
+ecstasy	B-Chemical
+users	O
+display	O
+impairments	B-Disease
+in	I-Disease
+learning	I-Disease
+and	I-Disease
+memory	I-Disease
+performance	O
+.	O
+
+In	O
+addition	O
+,	O
+working	O
+memory	O
+processing	O
+in	O
+ecstasy	B-Chemical
+users	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+associated	O
+with	O
+neural	O
+alterations	O
+in	O
+hippocampal	O
+and	O
+/	O
+or	O
+cortical	O
+regions	O
+as	O
+measured	O
+by	O
+functional	O
+magnetic	O
+resonance	O
+imaging	O
+(	O
+fMRI	O
+)	O
+.	O
+
+Using	O
+functional	O
+imaging	O
+and	O
+a	O
+face	O
+-	O
+learning	O
+task	O
+,	O
+we	O
+investigated	O
+neural	O
+correlates	O
+of	O
+encoding	O
+and	O
+recalling	O
+face	O
+-	O
+name	O
+associations	O
+in	O
+20	O
+recreational	O
+drug	O
+users	O
+whose	O
+predominant	O
+drug	O
+use	O
+was	O
+ecstasy	B-Chemical
+and	O
+20	O
+controls	O
+.	O
+
+To	O
+address	O
+the	O
+potential	O
+confounding	O
+effects	O
+of	O
+the	O
+cannabis	B-Chemical
+use	O
+of	O
+the	O
+ecstasy	B-Chemical
+using	O
+group	O
+,	O
+a	O
+second	O
+analysis	O
+included	O
+14	O
+previously	O
+tested	O
+cannabis	B-Chemical
+users	O
+(	O
+Nestor	O
+,	O
+L	O
+.	O
+,	O
+Roberts	O
+,	O
+G	O
+.	O
+,	O
+Garavan	O
+,	O
+H	O
+.	O
+,	O
+Hester	O
+,	O
+R	O
+.	O
+,	O
+2008	O
+.	O
+Deficits	B-Disease
+in	I-Disease
+learning	I-Disease
+and	I-Disease
+memory	I-Disease
+:	O
+parahippocampal	O
+hyperactivity	B-Disease
+and	O
+frontocortical	O
+hypoactivity	O
+in	O
+cannabis	B-Chemical
+users	O
+.	O
+Neuroimage	O
+40	O
+,	O
+1328	O
+-	O
+1339	O
+)	O
+.	O
+
+Ecstasy	B-Chemical
+users	O
+performed	O
+significantly	O
+worse	O
+in	O
+learning	O
+and	O
+memory	O
+compared	O
+to	O
+controls	O
+and	O
+cannabis	B-Chemical
+users	O
+.	O
+
+A	O
+conjunction	O
+analysis	O
+of	O
+the	O
+encode	O
+and	O
+recall	O
+phases	O
+of	O
+the	O
+task	O
+revealed	O
+ecstasy	B-Chemical
+-	O
+specific	O
+hyperactivity	B-Disease
+in	O
+bilateral	O
+frontal	O
+regions	O
+,	O
+left	O
+temporal	O
+,	O
+right	O
+parietal	O
+,	O
+bilateral	O
+temporal	O
+,	O
+and	O
+bilateral	O
+occipital	O
+brain	O
+regions	O
+.	O
+
+Ecstasy	B-Chemical
+-	O
+specific	O
+hypoactivity	O
+was	O
+evident	O
+in	O
+the	O
+right	O
+dorsal	O
+anterior	O
+cingulated	O
+cortex	O
+(	O
+ACC	O
+)	O
+and	O
+left	O
+posterior	O
+cingulated	O
+cortex	O
+.	O
+
+In	O
+both	O
+ecstasy	B-Chemical
+and	O
+cannabis	B-Chemical
+groups	O
+brain	O
+activation	O
+was	O
+decreased	O
+in	O
+the	O
+right	O
+medial	O
+frontal	O
+gyrus	O
+,	O
+left	O
+parahippocampal	O
+gyrus	O
+,	O
+left	O
+dorsal	O
+cingulate	O
+gyrus	O
+,	O
+and	O
+left	O
+caudate	O
+.	O
+
+These	O
+results	O
+elucidated	O
+ecstasy	B-Chemical
+-	O
+related	O
+deficits	O
+,	O
+only	O
+some	O
+of	O
+which	O
+might	O
+be	O
+attributed	O
+to	O
+cannabis	B-Chemical
+use	O
+.	O
+
+These	O
+ecstasy	B-Chemical
+-	O
+specific	O
+effects	O
+may	O
+be	O
+related	O
+to	O
+the	O
+vulnerability	O
+of	O
+isocortical	O
+and	O
+allocortical	O
+regions	O
+to	O
+the	O
+neurotoxic	B-Disease
+effects	O
+of	O
+ecstasy	B-Chemical
+.	O
+
+Disulfiram	B-Chemical
+-	O
+like	O
+syndrome	O
+after	O
+hydrogen	B-Chemical
+cyanamide	I-Chemical
+professional	O
+skin	O
+exposure	O
+:	O
+two	O
+case	O
+reports	O
+in	O
+France	O
+.	O
+
+Hydrogen	B-Chemical
+cyanamide	I-Chemical
+is	O
+a	O
+plant	O
+growth	O
+regulator	O
+used	O
+in	O
+agriculture	O
+to	O
+induce	O
+bud	O
+break	O
+in	O
+fruit	O
+trees	O
+.	O
+
+Contact	O
+with	O
+the	O
+skin	O
+can	O
+result	O
+in	O
+percutaneous	O
+absorption	O
+of	O
+the	O
+substance	O
+that	O
+inhibits	O
+aldehyde	B-Chemical
+dehydrogenase	O
+and	O
+can	O
+induce	O
+acetaldehyde	B-Chemical
+syndrome	O
+in	O
+case	O
+of	O
+alcohol	B-Chemical
+use	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+report	O
+is	O
+to	O
+describe	O
+two	O
+cases	O
+of	O
+a	O
+disulfiram	B-Chemical
+-	O
+like	O
+syndrome	O
+following	O
+occupational	O
+exposure	O
+to	O
+hydrogen	B-Chemical
+cyanamide	I-Chemical
+.	O
+
+The	O
+first	O
+case	O
+involved	O
+a	O
+59	O
+-	O
+year	O
+-	O
+old	O
+man	O
+who	O
+used	O
+Dormex	B-Chemical
+,	O
+which	O
+contains	O
+hydrogen	B-Chemical
+cyanamide	I-Chemical
+,	O
+without	O
+protection	O
+after	O
+consuming	O
+a	O
+large	O
+amount	O
+of	O
+alcohol	B-Chemical
+during	O
+a	O
+meal	O
+.	O
+
+In	O
+less	O
+than	O
+1	O
+hour	O
+after	O
+the	O
+ingestion	O
+of	O
+alcohol	B-Chemical
+,	O
+he	O
+developed	O
+malaise	O
+with	O
+flushing	B-Disease
+of	I-Disease
+the	I-Disease
+face	I-Disease
+,	O
+tachycardia	B-Disease
+,	O
+and	O
+dyspnea	B-Disease
+.	O
+
+Manifestations	O
+regressed	O
+spontaneously	O
+under	O
+surveillance	O
+in	O
+the	O
+hospital	O
+.	O
+
+The	O
+second	O
+case	O
+occurred	O
+in	O
+a	O
+55	O
+-	O
+year	O
+-	O
+old	O
+farmer	O
+following	O
+cutaneous	O
+contact	O
+with	O
+Dormex	B-Chemical
+.	O
+
+Five	O
+hours	O
+after	O
+exposure	O
+,	O
+he	O
+developed	O
+disulfiram	B-Chemical
+-	O
+like	O
+syndrome	O
+with	O
+flushing	B-Disease
+,	O
+tachycardia	B-Disease
+,	O
+and	O
+arterial	B-Disease
+hypotension	I-Disease
+after	O
+consuming	O
+three	O
+glasses	O
+of	O
+wine	O
+.	O
+
+The	O
+patient	O
+recovered	O
+spontaneously	O
+in	O
+3	O
+hours	O
+under	O
+surveillance	O
+in	O
+the	O
+hospital	O
+.	O
+
+These	O
+cases	O
+confirm	O
+the	O
+necessity	O
+of	O
+avoiding	O
+alcohol	B-Chemical
+consumption	O
+as	O
+recommended	O
+in	O
+the	O
+instructions	O
+for	O
+use	O
+of	O
+Dormex	B-Chemical
+and	O
+of	O
+preventing	O
+cutaneous	O
+contact	O
+during	O
+use	O
+.	O
+
+Sulpiride	B-Chemical
+-	O
+induced	O
+tardive	B-Disease
+dystonia	I-Disease
+.	O
+
+Sulpiride	B-Chemical
+is	O
+a	O
+selective	O
+D2	O
+-	O
+receptor	O
+antagonist	O
+with	O
+antipsychotic	O
+and	O
+antidepressant	B-Chemical
+properties	O
+.	O
+
+Although	O
+initially	O
+thought	O
+to	O
+be	O
+free	O
+of	O
+extrapyramidal	O
+side	O
+effects	O
+,	O
+sulpiride	B-Chemical
+-	O
+induced	O
+tardive	B-Disease
+dyskinesia	I-Disease
+and	O
+parkinsonism	B-Disease
+have	O
+been	O
+reported	O
+occasionally	O
+.	O
+
+We	O
+studied	O
+a	O
+37	O
+-	O
+year	O
+-	O
+old	O
+man	O
+who	O
+developed	O
+persistent	O
+segmental	O
+dystonia	B-Disease
+within	O
+2	O
+months	O
+after	O
+starting	O
+sulpiride	B-Chemical
+therapy	O
+.	O
+
+We	O
+could	O
+not	O
+find	O
+any	O
+previous	O
+reports	O
+of	O
+sulpiride	B-Chemical
+-	O
+induced	O
+tardive	B-Disease
+dystonia	I-Disease
+.	O
+
+Comparative	O
+cognitive	O
+and	O
+subjective	O
+side	O
+effects	O
+of	O
+immediate	O
+-	O
+release	O
+oxycodone	B-Chemical
+in	O
+healthy	O
+middle	O
+-	O
+aged	O
+and	O
+older	O
+adults	O
+.	O
+
+This	O
+study	O
+measured	O
+the	O
+objective	O
+and	O
+subjective	O
+neurocognitive	O
+effects	O
+of	O
+a	O
+single	O
+10	O
+-	O
+mg	O
+dose	O
+of	O
+immediate	O
+-	O
+release	O
+oxycodone	B-Chemical
+in	O
+healthy	O
+,	O
+older	O
+(	O
+>	O
+65	O
+years	O
+)	O
+,	O
+and	O
+middle	O
+-	O
+aged	O
+(	O
+35	O
+to	O
+55	O
+years	O
+)	O
+adults	O
+who	O
+were	O
+not	O
+suffering	O
+from	O
+chronic	O
+or	O
+significant	O
+daily	O
+pain	B-Disease
+.	O
+
+Seventy	O
+-	O
+one	O
+participants	O
+completed	O
+2	O
+separate	O
+study	O
+days	O
+and	O
+were	O
+blind	O
+to	O
+medication	O
+condition	O
+(	O
+placebo	O
+,	O
+10	O
+-	O
+mg	O
+oxycodone	B-Chemical
+)	O
+.	O
+
+Plasma	O
+oxycodone	B-Chemical
+concentration	O
+peaked	O
+between	O
+60	O
+and	O
+90	O
+minutes	O
+postdose	O
+(	O
+P	O
+<	O
+.	O
+01	O
+)	O
+and	O
+pupil	O
+size	O
+,	O
+an	O
+indication	O
+of	O
+physiological	O
+effects	O
+of	O
+the	O
+medication	O
+,	O
+peaked	O
+at	O
+approximately	O
+90	O
+to	O
+120	O
+minutes	O
+postdose	O
+(	O
+P	O
+<	O
+.	O
+01	O
+)	O
+.	O
+
+Significant	O
+declines	B-Disease
+in	I-Disease
+simple	I-Disease
+and	I-Disease
+sustained	I-Disease
+attention	I-Disease
+,	I-Disease
+working	I-Disease
+memory	I-Disease
+,	I-Disease
+and	I-Disease
+verbal	I-Disease
+memory	I-Disease
+were	O
+observed	O
+at	O
+1	O
+hour	O
+postdose	O
+compared	O
+to	O
+baseline	O
+for	O
+both	O
+age	O
+groups	O
+with	O
+a	O
+trend	O
+toward	O
+return	O
+to	O
+baseline	O
+by	O
+5	O
+hours	O
+postdose	O
+.	O
+
+For	O
+almost	O
+all	O
+cognitive	O
+measures	O
+,	O
+there	O
+were	O
+no	O
+medication	O
+by	O
+age	O
+-	O
+interaction	O
+effects	O
+,	O
+which	O
+indicates	O
+that	O
+the	O
+2	O
+age	O
+groups	O
+exhibited	O
+similar	O
+responses	O
+to	O
+the	O
+medication	O
+challenge	O
+.	O
+
+This	O
+study	O
+suggests	O
+that	O
+for	O
+healthy	O
+older	O
+adults	O
+who	O
+are	O
+not	O
+suffering	O
+from	O
+chronic	B-Disease
+pain	I-Disease
+,	O
+neurocognitive	O
+and	O
+pharmacodynamic	O
+changes	O
+in	O
+response	O
+to	O
+a	O
+10	O
+-	O
+mg	O
+dose	O
+of	O
+immediate	O
+-	O
+release	O
+oxycodone	B-Chemical
+are	O
+similar	O
+to	O
+those	O
+observed	O
+for	O
+middle	O
+-	O
+aged	O
+adults	O
+.	O
+
+PERSPECTIVE	O
+:	O
+Study	O
+findings	O
+indicate	O
+that	O
+the	O
+metabolism	O
+,	O
+neurocognitive	O
+effects	O
+,	O
+and	O
+physical	O
+side	O
+effects	O
+of	O
+oral	O
+oxycodone	B-Chemical
+are	O
+similar	O
+for	O
+healthy	O
+middle	O
+-	O
+aged	O
+and	O
+older	O
+adults	O
+.	O
+
+Therefore	O
+,	O
+clinicians	O
+should	O
+not	O
+avoid	O
+prescribing	O
+oral	O
+opioids	O
+to	O
+older	O
+adults	O
+based	O
+on	O
+the	O
+belief	O
+that	O
+older	O
+adults	O
+are	O
+at	O
+higher	O
+risk	O
+for	O
+side	O
+effects	O
+than	O
+younger	O
+adults	O
+.	O
+
+The	O
+glycine	B-Chemical
+transporter	O
+-	O
+1	O
+inhibitor	O
+SSR103800	B-Chemical
+displays	O
+a	O
+selective	O
+and	O
+specific	O
+antipsychotic	O
+-	O
+like	O
+profile	O
+in	O
+normal	O
+and	O
+transgenic	O
+mice	O
+.	O
+
+Schizophrenia	B-Disease
+has	O
+been	O
+initially	O
+associated	O
+with	O
+dysfunction	O
+in	O
+dopamine	B-Chemical
+neurotransmission	O
+.	O
+
+However	O
+,	O
+the	O
+observation	O
+that	O
+antagonists	O
+of	O
+the	O
+glutamate	B-Chemical
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+D	I-Chemical
+-	I-Chemical
+aspartate	I-Chemical
+(	O
+NMDA	B-Chemical
+)	O
+receptor	O
+produce	O
+schizophrenic	B-Disease
+-	O
+like	O
+symptoms	O
+in	O
+humans	O
+has	O
+led	O
+to	O
+the	O
+idea	O
+of	O
+a	O
+dysfunctioning	O
+of	O
+the	O
+glutamatergic	O
+system	O
+via	O
+its	O
+NMDA	B-Chemical
+receptor	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+there	O
+is	O
+a	O
+growing	O
+interest	O
+in	O
+the	O
+development	O
+of	O
+pharmacological	O
+agents	O
+with	O
+potential	O
+antipsychotic	O
+properties	O
+that	O
+enhance	O
+the	O
+activity	O
+of	O
+the	O
+glutamatergic	O
+system	O
+via	O
+a	O
+modulation	O
+of	O
+the	O
+NMDA	B-Chemical
+receptor	O
+.	O
+
+Among	O
+them	O
+are	O
+glycine	B-Chemical
+transporter	O
+-	O
+1	O
+(	O
+GlyT1	O
+)	O
+inhibitors	O
+such	O
+as	O
+SSR103800	B-Chemical
+,	O
+which	O
+indirectly	O
+enhance	O
+NMDA	B-Chemical
+receptor	O
+function	O
+by	O
+increasing	O
+the	O
+glycine	B-Chemical
+(	O
+a	O
+co	O
+-	O
+agonist	O
+for	O
+the	O
+NMDA	B-Chemical
+receptor	O
+)	O
+levels	O
+in	O
+the	O
+synapse	O
+.	O
+
+This	O
+study	O
+aimed	O
+at	O
+investigating	O
+the	O
+potential	O
+antipsychotic	O
+-	O
+like	O
+properties	O
+of	O
+SSR103800	B-Chemical
+,	O
+with	O
+a	O
+particular	O
+focus	O
+on	O
+models	O
+of	O
+hyperactivity	B-Disease
+,	O
+involving	O
+either	O
+drug	O
+challenge	O
+(	O
+ie	O
+,	O
+amphetamine	B-Chemical
+and	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+)	O
+or	O
+transgenic	O
+mice	O
+(	O
+ie	O
+,	O
+NMDA	B-Chemical
+Nr1	O
+(	O
+neo	O
+-	O
+/	O
+-	O
+)	O
+and	O
+DAT	O
+(	O
+-	O
+/	O
+-	O
+)	O
+)	O
+.	O
+
+Results	O
+showed	O
+that	O
+SSR103800	B-Chemical
+(	O
+10	O
+-	O
+30	O
+mg	O
+/	O
+kg	O
+p	O
+.	O
+o	O
+.	O
+)	O
+blocked	O
+hyperactivity	B-Disease
+induced	O
+by	O
+the	O
+non	O
+-	O
+competitive	O
+NMDA	B-Chemical
+receptor	O
+antagonist	O
+,	O
+MK	B-Chemical
+-	I-Chemical
+801	I-Chemical
+and	O
+partially	O
+reversed	O
+spontaneous	O
+hyperactivity	B-Disease
+of	O
+NMDA	B-Chemical
+Nr1	O
+(	O
+neo	O
+-	O
+/	O
+-	O
+)	O
+mice	O
+.	O
+
+In	O
+contrast	O
+,	O
+SSR103800	B-Chemical
+failed	O
+to	O
+affect	O
+hyperactivity	B-Disease
+induced	O
+by	O
+amphetamine	B-Chemical
+or	O
+naturally	O
+observed	O
+in	O
+dopamine	B-Chemical
+transporter	O
+(	O
+DAT	O
+(	O
+-	O
+/	O
+-	O
+)	O
+)	O
+knockout	O
+mice	O
+(	O
+10	O
+-	O
+30	O
+mg	O
+/	O
+kg	O
+p	O
+.	O
+o	O
+.	O
+)	O
+.	O
+
+Importantly	O
+,	O
+both	O
+classical	O
+(	O
+haloperidol	B-Chemical
+)	O
+and	O
+atypical	O
+(	O
+olanzapine	B-Chemical
+,	O
+clozapine	B-Chemical
+and	O
+aripiprazole	B-Chemical
+)	O
+antipsychotics	O
+were	O
+effective	O
+in	O
+all	O
+these	O
+models	O
+of	O
+hyperactivity	B-Disease
+.	O
+
+However	O
+,	O
+unlike	O
+these	O
+latter	O
+,	O
+SSR103800	B-Chemical
+did	O
+not	O
+produce	O
+catalepsy	B-Disease
+(	O
+retention	O
+on	O
+the	O
+bar	O
+test	O
+)	O
+up	O
+to	O
+30	O
+mg	O
+/	O
+kg	O
+p	O
+.	O
+o	O
+.	O
+
+Together	O
+these	O
+findings	O
+show	O
+that	O
+the	O
+GlyT1	O
+inhibitor	O
+,	O
+SSR103800	B-Chemical
+,	O
+produces	O
+antipsychotic	O
+-	O
+like	O
+effects	O
+,	O
+which	O
+differ	O
+from	O
+those	O
+observed	O
+with	O
+compounds	O
+primarily	O
+targeting	O
+the	O
+dopaminergic	O
+system	O
+,	O
+and	O
+has	O
+a	O
+reduced	O
+side	O
+-	O
+effect	O
+potential	O
+as	O
+compared	O
+with	O
+these	O
+latter	O
+drugs	O
+.	O
+
+Pyrrolidine	B-Chemical
+dithiocarbamate	I-Chemical
+protects	O
+the	O
+piriform	O
+cortex	O
+in	O
+the	O
+pilocarpine	B-Chemical
+status	B-Disease
+epilepticus	I-Disease
+model	O
+.	O
+
+Pyrrolidine	B-Chemical
+dithiocarbamate	I-Chemical
+(	O
+PDTC	B-Chemical
+)	O
+has	O
+a	O
+dual	O
+mechanism	O
+of	O
+action	O
+as	O
+an	O
+antioxidant	O
+and	O
+an	O
+inhibitor	O
+of	O
+the	O
+transcription	O
+factor	O
+kappa	O
+-	O
+beta	O
+.	O
+
+Both	O
+,	O
+production	O
+of	O
+reactive	O
+oxygen	B-Chemical
+species	O
+as	O
+well	O
+as	O
+activation	O
+of	O
+NF	O
+-	O
+kappaB	O
+have	O
+been	O
+implicated	O
+in	O
+severe	O
+neuronal	B-Disease
+damage	I-Disease
+in	O
+different	O
+sub	O
+-	O
+regions	O
+of	O
+the	O
+hippocampus	O
+as	O
+well	O
+as	O
+in	O
+the	O
+surrounding	O
+cortices	O
+.	O
+
+The	O
+effect	O
+of	O
+PDTC	B-Chemical
+on	O
+status	B-Disease
+epilepticus	I-Disease
+-	O
+associated	O
+cell	O
+loss	O
+in	O
+the	O
+hippocampus	O
+and	O
+piriform	O
+cortex	O
+was	O
+evaluated	O
+in	O
+the	O
+rat	O
+fractionated	O
+pilocarpine	B-Chemical
+model	O
+.	O
+
+Treatment	O
+with	O
+150	O
+mg	O
+/	O
+kg	O
+PDTC	B-Chemical
+before	O
+and	O
+following	O
+status	B-Disease
+epilepticus	I-Disease
+significantly	O
+increased	O
+the	O
+mortality	O
+rate	O
+to	O
+100	O
+%	O
+.	O
+
+Administration	O
+of	O
+50	O
+mg	O
+/	O
+kg	O
+PDTC	B-Chemical
+(	O
+low	O
+-	O
+dose	O
+)	O
+did	O
+not	O
+exert	O
+major	O
+effects	O
+on	O
+the	O
+development	O
+of	O
+a	O
+status	B-Disease
+epilepticus	I-Disease
+or	O
+the	O
+mortality	O
+rate	O
+.	O
+
+In	O
+vehicle	O
+-	O
+treated	O
+rats	O
+,	O
+status	B-Disease
+epilepticus	I-Disease
+caused	O
+pronounced	O
+neuronal	B-Disease
+damage	I-Disease
+in	O
+the	O
+piriform	O
+cortex	O
+comprising	O
+both	O
+pyramidal	O
+cells	O
+and	O
+interneurons	O
+.	O
+
+Low	O
+-	O
+dose	O
+PDTC	B-Chemical
+treatment	O
+almost	O
+completely	O
+protected	O
+from	O
+lesions	O
+in	O
+the	O
+piriform	O
+cortex	O
+.	O
+
+A	O
+significant	O
+decrease	O
+in	O
+neuronal	O
+density	O
+of	O
+the	O
+hippocampal	O
+hilar	O
+formation	O
+was	O
+identified	O
+in	O
+vehicle	O
+-	O
+and	O
+PDTC	B-Chemical
+-	O
+treated	O
+rats	O
+following	O
+status	B-Disease
+epilepticus	I-Disease
+.	O
+
+In	O
+conclusion	O
+,	O
+the	O
+NF	O
+-	O
+kappaB	O
+inhibitor	O
+and	O
+antioxidant	O
+PDTC	B-Chemical
+protected	O
+the	O
+piriform	O
+cortex	O
+,	O
+whereas	O
+it	O
+did	O
+not	O
+affect	O
+hilar	O
+neuronal	B-Disease
+loss	I-Disease
+.	O
+
+These	O
+data	O
+might	O
+indicate	O
+that	O
+the	O
+generation	O
+of	O
+reactive	O
+oxygen	B-Chemical
+species	O
+and	O
+activation	O
+of	O
+NF	O
+-	O
+kappaB	O
+plays	O
+a	O
+more	O
+central	O
+role	O
+in	O
+seizure	B-Disease
+-	O
+associated	O
+neuronal	B-Disease
+damage	I-Disease
+in	O
+the	O
+temporal	O
+cortex	O
+as	O
+compared	O
+to	O
+the	O
+hippocampal	O
+hilus	O
+.	O
+
+However	O
+,	O
+future	O
+investigations	O
+are	O
+necessary	O
+to	O
+exactly	O
+analyze	O
+the	O
+biochemical	O
+mechanisms	O
+by	O
+which	O
+PDTC	B-Chemical
+exerted	O
+its	O
+beneficial	O
+effects	O
+in	O
+the	O
+piriform	O
+cortex	O
+.	O
+
+Anaesthetists	O
+'	O
+nightmare	O
+:	O
+masseter	B-Disease
+spasm	I-Disease
+after	O
+induction	O
+in	O
+an	O
+undiagnosed	O
+case	O
+of	O
+myotonia	B-Disease
+congenita	I-Disease
+.	O
+
+We	O
+report	O
+an	O
+undiagnosed	O
+case	O
+of	O
+myotonia	B-Disease
+congenita	I-Disease
+in	O
+a	O
+24	O
+-	O
+year	O
+-	O
+old	O
+previously	O
+healthy	O
+primigravida	O
+,	O
+who	O
+developed	O
+life	O
+threatening	O
+masseter	B-Disease
+spasm	I-Disease
+following	O
+a	O
+standard	O
+dose	O
+of	O
+intravenous	O
+suxamethonium	B-Chemical
+for	O
+induction	O
+of	O
+anaesthesia	O
+.	O
+
+Neither	O
+the	O
+patient	O
+nor	O
+the	O
+anaesthetist	O
+was	O
+aware	O
+of	O
+the	O
+diagnosis	O
+before	O
+this	O
+potentially	O
+lethal	O
+complication	O
+occurred	O
+.	O
+
+Twin	O
+preterm	O
+neonates	O
+with	O
+cardiac	B-Disease
+toxicity	I-Disease
+related	O
+to	O
+lopinavir	B-Chemical
+/	I-Chemical
+ritonavir	I-Chemical
+therapy	O
+.	O
+
+We	O
+report	O
+twin	O
+neonates	O
+who	O
+were	O
+born	O
+prematurely	O
+at	O
+32	O
+weeks	O
+of	O
+gestation	O
+to	O
+a	O
+mother	O
+with	O
+human	B-Disease
+immunodeficiency	I-Disease
+virus	I-Disease
+infection	I-Disease
+.	O
+
+One	O
+of	O
+the	O
+twins	O
+developed	O
+complete	O
+heart	B-Disease
+block	I-Disease
+and	O
+dilated	B-Disease
+cardiomyopathy	I-Disease
+related	O
+to	O
+lopinavir	B-Chemical
+/	I-Chemical
+ritonavir	I-Chemical
+therapy	O
+,	O
+a	O
+boosted	O
+protease	O
+-	O
+inhibitor	O
+agent	O
+,	O
+while	O
+the	O
+other	O
+twin	O
+developed	O
+mild	O
+bradycardia	B-Disease
+.	O
+
+We	O
+recommend	O
+caution	O
+in	O
+the	O
+use	O
+of	O
+lopinavir	B-Chemical
+/	I-Chemical
+ritonavir	I-Chemical
+in	O
+the	O
+immediate	O
+neonatal	O
+period	O
+.	O
+
+When	O
+drugs	O
+disappear	O
+from	O
+the	O
+patient	O
+:	O
+elimination	O
+of	O
+intravenous	O
+medication	O
+by	O
+hemodiafiltration	O
+.	O
+
+Twenty	O
+-	O
+three	O
+hours	O
+after	O
+heart	O
+transplantation	O
+,	O
+life	O
+-	O
+threatening	O
+acute	O
+right	B-Disease
+heart	I-Disease
+failure	I-Disease
+was	O
+diagnosed	O
+in	O
+a	O
+patient	O
+requiring	O
+continuous	O
+venovenous	O
+hemodiafiltration	O
+(	O
+CVVHDF	O
+)	O
+.	O
+
+Increasing	O
+doses	O
+of	O
+catecholamines	B-Chemical
+,	O
+sedatives	O
+,	O
+and	O
+muscle	O
+relaxants	O
+administered	O
+through	O
+a	O
+central	O
+venous	O
+catheter	O
+were	O
+ineffective	O
+.	O
+
+However	O
+,	O
+a	O
+bolus	O
+of	O
+epinephrine	B-Chemical
+injected	O
+through	O
+an	O
+alternative	O
+catheter	O
+provoked	O
+a	O
+hypertensive	B-Disease
+crisis	O
+.	O
+
+Thus	O
+,	O
+interference	O
+with	O
+the	O
+central	O
+venous	O
+infusion	O
+by	O
+the	O
+dialysis	O
+catheter	O
+was	O
+suspected	O
+.	O
+
+The	O
+catheters	O
+were	O
+changed	O
+,	O
+and	O
+hemodynamics	O
+stabilized	O
+at	O
+lower	O
+catecholamine	B-Chemical
+doses	O
+.	O
+
+When	O
+the	O
+effects	O
+of	O
+IV	O
+drugs	O
+are	O
+inadequate	O
+in	O
+patients	O
+receiving	O
+CVVHDF	O
+,	O
+interference	O
+with	O
+adjacent	O
+catheters	O
+resulting	O
+in	O
+elimination	O
+of	O
+the	O
+drug	O
+by	O
+CVVHDF	O
+should	O
+be	O
+suspected	O
+.	O
+
+Less	O
+frequent	O
+lithium	B-Chemical
+administration	O
+and	O
+lower	O
+urine	O
+volume	O
+.	O
+
+OBJECTIVE	O
+:	O
+This	O
+study	O
+was	O
+designed	O
+to	O
+determine	O
+whether	O
+patients	O
+maintained	O
+on	O
+a	O
+regimen	O
+of	O
+lithium	B-Chemical
+on	O
+a	O
+once	O
+-	O
+per	O
+-	O
+day	O
+schedule	O
+have	O
+lower	O
+urine	O
+volumes	O
+than	O
+do	O
+patients	O
+receiving	O
+multiple	O
+doses	O
+per	O
+day	O
+.	O
+
+METHOD	O
+:	O
+This	O
+was	O
+a	O
+cross	O
+-	O
+sectional	O
+study	O
+of	O
+85	O
+patients	O
+from	O
+a	O
+lithium	B-Chemical
+clinic	O
+who	O
+received	O
+different	O
+dose	O
+schedules	O
+.	O
+
+Patients	O
+were	O
+admitted	O
+to	O
+the	O
+hospital	O
+for	O
+measurement	O
+of	O
+lithium	B-Chemical
+level	O
+,	O
+creatinine	B-Chemical
+clearance	O
+,	O
+urine	O
+volume	O
+,	O
+and	O
+maximum	O
+osmolality	O
+.	O
+
+RESULTS	O
+:	O
+Multiple	O
+daily	O
+doses	O
+of	O
+lithium	B-Chemical
+were	O
+associated	O
+with	O
+higher	O
+urine	O
+volumes	O
+.	O
+
+The	O
+dosing	O
+schedule	O
+,	O
+duration	O
+of	O
+lithium	B-Chemical
+treatment	O
+,	O
+and	O
+daily	O
+dose	O
+of	O
+lithium	B-Chemical
+did	O
+not	O
+affect	O
+maximum	O
+osmolality	O
+or	O
+creatinine	B-Chemical
+clearance	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Urine	O
+volume	O
+can	O
+be	O
+reduced	O
+by	O
+giving	O
+lithium	B-Chemical
+once	O
+daily	O
+and	O
+/	O
+or	O
+by	O
+lowering	O
+the	O
+total	O
+daily	O
+dose	O
+.	O
+
+Lithium	B-Chemical
+-	O
+induced	O
+polyuria	B-Disease
+seems	O
+to	O
+be	O
+related	O
+to	O
+extrarenal	O
+as	O
+well	O
+as	O
+to	O
+renal	O
+effects	O
+.	O
+
+Antibacterial	O
+medication	O
+use	O
+during	O
+pregnancy	O
+and	O
+risk	O
+of	O
+birth	B-Disease
+defects	I-Disease
+:	O
+National	O
+Birth	B-Disease
+Defects	I-Disease
+Prevention	O
+Study	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+estimate	O
+the	O
+association	O
+between	O
+antibacterial	O
+medications	O
+and	O
+selected	O
+birth	B-Disease
+defects	I-Disease
+.	O
+
+DESIGN	O
+,	O
+SETTING	O
+,	O
+AND	O
+PARTICIPANTS	O
+:	O
+Population	O
+-	O
+based	O
+,	O
+multisite	O
+,	O
+case	O
+-	O
+control	O
+study	O
+of	O
+women	O
+who	O
+had	O
+pregnancies	O
+affected	O
+by	O
+1	O
+of	O
+more	O
+than	O
+30	O
+eligible	O
+major	O
+birth	B-Disease
+defects	I-Disease
+identified	O
+via	O
+birth	B-Disease
+defect	I-Disease
+surveillance	O
+programs	O
+in	O
+10	O
+states	O
+(	O
+n	O
+=	O
+13	O
+155	O
+)	O
+and	O
+control	O
+women	O
+randomly	O
+selected	O
+from	O
+the	O
+same	O
+geographical	O
+regions	O
+(	O
+n	O
+=	O
+4941	O
+)	O
+.	O
+
+MAIN	O
+EXPOSURE	O
+:	O
+Reported	O
+maternal	O
+use	O
+of	O
+antibacterials	O
+(	O
+1	O
+month	O
+before	O
+pregnancy	O
+through	O
+the	O
+end	O
+of	O
+the	O
+first	O
+trimester	O
+)	O
+.	O
+
+MAIN	O
+OUTCOME	O
+MEASURE	O
+:	O
+Odds	O
+ratios	O
+(	O
+ORs	O
+)	O
+measuring	O
+the	O
+association	O
+between	O
+antibacterial	O
+use	O
+and	O
+selected	O
+birth	B-Disease
+defects	I-Disease
+adjusted	O
+for	O
+potential	O
+confounders	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+reported	O
+use	O
+of	O
+antibacterials	O
+increased	O
+during	O
+pregnancy	O
+,	O
+peaking	O
+during	O
+the	O
+third	O
+month	O
+.	O
+
+Sulfonamides	B-Chemical
+were	O
+associated	O
+with	O
+anencephaly	B-Disease
+(	O
+adjusted	O
+OR	O
+[	O
+AOR	O
+]	O
+=	O
+3	O
+.	O
+4	O
+;	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+,	O
+1	O
+.	O
+3	O
+-	O
+8	O
+.	O
+8	O
+)	O
+,	O
+hypoplastic	B-Disease
+left	I-Disease
+heart	I-Disease
+syndrome	I-Disease
+(	O
+AOR	O
+=	O
+3	O
+.	O
+2	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+3	O
+-	O
+7	O
+.	O
+6	O
+)	O
+,	O
+coarctation	B-Disease
+of	I-Disease
+the	I-Disease
+aorta	I-Disease
+(	O
+AOR	O
+=	O
+2	O
+.	O
+7	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+3	O
+-	O
+5	O
+.	O
+6	O
+)	O
+,	O
+choanal	B-Disease
+atresia	I-Disease
+(	O
+AOR	O
+=	O
+8	O
+.	O
+0	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+2	O
+.	O
+7	O
+-	O
+23	O
+.	O
+5	O
+)	O
+,	O
+transverse	B-Disease
+limb	I-Disease
+deficiency	I-Disease
+(	O
+AOR	O
+=	O
+2	O
+.	O
+5	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+0	O
+-	O
+5	O
+.	O
+9	O
+)	O
+,	O
+and	O
+diaphragmatic	B-Disease
+hernia	I-Disease
+(	O
+AOR	O
+=	O
+2	O
+.	O
+4	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+1	O
+-	O
+5	O
+.	O
+4	O
+)	O
+.	O
+
+Nitrofurantoins	B-Chemical
+were	O
+associated	O
+with	O
+anophthalmia	B-Disease
+or	O
+microphthalmos	B-Disease
+(	O
+AOR	O
+=	O
+3	O
+.	O
+7	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+1	O
+-	O
+12	O
+.	O
+2	O
+)	O
+,	O
+hypoplastic	B-Disease
+left	I-Disease
+heart	I-Disease
+syndrome	I-Disease
+(	O
+AOR	O
+=	O
+4	O
+.	O
+2	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+9	O
+-	O
+9	O
+.	O
+1	O
+)	O
+,	O
+atrial	B-Disease
+septal	I-Disease
+defects	I-Disease
+(	O
+AOR	O
+=	O
+1	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+1	O
+-	O
+3	O
+.	O
+4	O
+)	O
+,	O
+and	O
+cleft	B-Disease
+lip	I-Disease
+with	O
+cleft	B-Disease
+palate	I-Disease
+(	O
+AOR	O
+=	O
+2	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+1	O
+.	O
+2	O
+-	O
+3	O
+.	O
+9	O
+)	O
+.	O
+
+Other	O
+antibacterial	O
+agents	O
+that	O
+showed	O
+associations	O
+included	O
+erythromycins	B-Chemical
+(	O
+2	O
+defects	O
+)	O
+,	O
+penicillins	B-Chemical
+(	O
+1	O
+defect	O
+)	O
+,	O
+cephalosporins	B-Chemical
+(	O
+1	O
+defect	O
+)	O
+,	O
+and	O
+quinolones	B-Chemical
+(	O
+1	O
+defect	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Reassuringly	O
+,	O
+penicillins	B-Chemical
+,	O
+erythromycins	B-Chemical
+,	O
+and	O
+cephalosporins	B-Chemical
+,	O
+although	O
+used	O
+commonly	O
+by	O
+pregnant	O
+women	O
+,	O
+were	O
+not	O
+associated	O
+with	O
+many	O
+birth	B-Disease
+defects	I-Disease
+.	O
+
+Sulfonamides	B-Chemical
+and	O
+nitrofurantoins	B-Chemical
+were	O
+associated	O
+with	O
+several	O
+birth	B-Disease
+defects	I-Disease
+,	O
+indicating	O
+a	O
+need	O
+for	O
+additional	O
+scrutiny	O
+.	O
+
+Differential	O
+impact	O
+of	O
+immune	O
+escape	O
+mutations	O
+G145R	O
+and	O
+P120T	O
+on	O
+the	O
+replication	O
+of	O
+lamivudine	B-Chemical
+-	O
+resistant	O
+hepatitis	B-Chemical
+B	I-Chemical
+virus	I-Chemical
+e	I-Chemical
+antigen	I-Chemical
+-	O
+positive	O
+and	O
+-	O
+negative	O
+strains	O
+.	O
+
+Immune	O
+escape	O
+variants	O
+of	O
+the	O
+hepatitis	B-Disease
+B	I-Disease
+virus	O
+(	O
+HBV	O
+)	O
+represent	O
+an	O
+emerging	O
+clinical	O
+challenge	O
+,	O
+because	O
+they	O
+can	O
+be	O
+associated	O
+with	O
+vaccine	O
+escape	O
+,	O
+HBV	O
+reactivation	O
+,	O
+and	O
+failure	O
+of	O
+diagnostic	O
+tests	O
+.	O
+
+Recent	O
+data	O
+suggest	O
+a	O
+preferential	O
+selection	O
+of	O
+immune	O
+escape	O
+mutants	O
+in	O
+distinct	O
+peripheral	O
+blood	O
+leukocyte	O
+compartments	O
+of	O
+infected	O
+individuals	O
+.	O
+
+We	O
+therefore	O
+systematically	O
+analyzed	O
+the	O
+functional	O
+impact	O
+of	O
+the	O
+most	O
+prevalent	O
+immune	O
+escape	O
+variants	O
+,	O
+the	O
+sG145R	O
+and	O
+sP120T	O
+mutants	O
+,	O
+on	O
+the	O
+viral	O
+replication	O
+efficacy	O
+and	O
+antiviral	O
+drug	O
+susceptibility	O
+of	O
+common	O
+treatment	O
+-	O
+associated	O
+mutants	O
+with	O
+resistance	O
+to	O
+lamivudine	B-Chemical
+(	O
+LAM	B-Chemical
+)	O
+and	O
+/	O
+or	O
+HBeAg	B-Chemical
+negativity	O
+.	O
+
+Replication	O
+-	O
+competent	O
+HBV	O
+strains	O
+with	O
+sG145R	O
+or	O
+sP120T	O
+and	O
+LAM	B-Chemical
+resistance	O
+(	O
+rtM204I	O
+or	O
+rtL180M	O
+/	O
+rtM204V	O
+)	O
+were	O
+generated	O
+on	O
+an	O
+HBeAg	B-Chemical
+-	O
+positive	O
+and	O
+an	O
+HBeAg	B-Chemical
+-	O
+negative	O
+background	O
+with	O
+precore	O
+(	O
+PC	O
+)	O
+and	O
+basal	O
+core	O
+promoter	O
+(	O
+BCP	O
+)	O
+mutants	O
+.	O
+
+The	O
+sG145R	O
+mutation	O
+strongly	O
+reduced	O
+HBsAg	B-Chemical
+levels	O
+and	O
+was	O
+able	O
+to	O
+fully	O
+restore	O
+the	O
+impaired	O
+replication	O
+of	O
+LAM	B-Chemical
+-	O
+resistant	O
+HBV	O
+mutants	O
+to	O
+the	O
+levels	O
+of	O
+wild	O
+-	O
+type	O
+HBV	O
+,	O
+and	O
+PC	O
+or	O
+BCP	O
+mutations	O
+further	O
+enhanced	O
+viral	O
+replication	O
+.	O
+
+Although	O
+the	O
+sP120T	O
+substitution	O
+also	O
+impaired	O
+HBsAg	B-Chemical
+secretion	O
+,	O
+it	O
+did	O
+not	O
+enhance	O
+the	O
+replication	O
+of	O
+LAM	B-Chemical
+-	O
+resistant	O
+clones	O
+.	O
+
+However	O
+,	O
+the	O
+concomitant	O
+occurrence	O
+of	O
+HBeAg	B-Chemical
+negativity	O
+(	O
+PC	O
+/	O
+BCP	O
+)	O
+,	O
+sP120T	O
+,	O
+and	O
+LAM	B-Chemical
+resistance	O
+resulted	O
+in	O
+the	O
+restoration	O
+of	O
+replication	O
+to	O
+levels	O
+of	O
+wild	O
+-	O
+type	O
+HBV	O
+.	O
+
+In	O
+all	O
+clones	O
+with	O
+combined	O
+immune	O
+escape	O
+and	O
+LAM	B-Chemical
+resistance	O
+mutations	O
+,	O
+the	O
+nucleotide	B-Chemical
+analogues	O
+adefovir	B-Chemical
+and	O
+tenofovir	B-Chemical
+remained	O
+effective	O
+in	O
+suppressing	O
+viral	O
+replication	O
+in	O
+vitro	O
+.	O
+
+These	O
+findings	O
+reveal	O
+the	O
+differential	O
+impact	O
+of	O
+immune	O
+escape	O
+variants	O
+on	O
+the	O
+replication	O
+and	O
+drug	O
+susceptibility	O
+of	O
+complex	O
+HBV	O
+mutants	O
+,	O
+supporting	O
+the	O
+need	O
+of	O
+close	O
+surveillance	O
+and	O
+treatment	O
+adjustment	O
+in	O
+response	O
+to	O
+the	O
+selection	O
+of	O
+distinct	O
+mutational	O
+patterns	O
+.	O
+
+Hemolytic	B-Disease
+anemia	I-Disease
+associated	O
+with	O
+the	O
+use	O
+of	O
+omeprazole	B-Chemical
+.	O
+
+Omeprazole	B-Chemical
+is	O
+the	O
+first	O
+drug	O
+designed	O
+to	O
+block	O
+the	O
+final	O
+step	O
+in	O
+the	O
+acid	O
+secretory	O
+process	O
+within	O
+the	O
+parietal	O
+cell	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+extremely	O
+effective	O
+in	O
+the	O
+treatment	O
+of	O
+peptic	B-Disease
+ulcer	I-Disease
+disease	I-Disease
+,	O
+reflux	B-Disease
+esophagitis	I-Disease
+,	O
+and	O
+the	O
+Zollinger	B-Disease
+-	I-Disease
+Ellison	I-Disease
+syndrome	I-Disease
+.	O
+
+Although	O
+clinical	O
+experience	O
+with	O
+omeprazole	B-Chemical
+is	O
+still	O
+limited	O
+,	O
+many	O
+controlled	O
+studies	O
+have	O
+established	O
+the	O
+short	O
+-	O
+term	O
+safety	O
+of	O
+this	O
+drug	O
+.	O
+
+We	O
+report	O
+the	O
+first	O
+case	O
+of	O
+a	O
+serious	O
+short	O
+-	O
+term	O
+adverse	O
+reaction	O
+with	O
+the	O
+use	O
+of	O
+omeprazole	B-Chemical
+:	O
+hemolytic	B-Disease
+anemia	I-Disease
+.	O
+
+The	O
+patient	O
+developed	O
+weakness	O
+,	O
+lethargy	B-Disease
+,	O
+and	O
+shortness	B-Disease
+of	I-Disease
+breath	I-Disease
+2	O
+days	O
+after	O
+starting	O
+therapy	O
+with	O
+omeprazole	B-Chemical
+.	O
+
+Two	O
+weeks	O
+after	O
+the	O
+initiation	O
+of	O
+therapy	O
+,	O
+her	O
+hematocrit	O
+had	O
+decreased	O
+from	O
+44	O
+.	O
+1	O
+%	O
+to	O
+20	O
+.	O
+4	O
+%	O
+,	O
+and	O
+she	O
+had	O
+a	O
+positive	O
+direct	O
+Coombs	O
+antiglobulin	O
+test	O
+and	O
+an	O
+elevated	O
+indirect	O
+bilirubin	B-Chemical
+.	O
+
+After	O
+she	O
+discontinued	O
+the	O
+omeprazole	B-Chemical
+,	O
+her	O
+hemoglobin	O
+and	O
+hematocrit	O
+gradually	O
+returned	O
+to	O
+normal	O
+.	O
+
+The	O
+mechanism	O
+by	O
+which	O
+omeprazole	B-Chemical
+caused	O
+the	O
+patient	O
+'	O
+s	O
+hemolytic	B-Disease
+anemia	I-Disease
+is	O
+uncertain	O
+,	O
+but	O
+physicians	O
+should	O
+be	O
+alerted	O
+to	O
+this	O
+possible	O
+adverse	O
+effect	O
+.	O
+
+Phenylephrine	B-Chemical
+but	O
+not	O
+ephedrine	B-Chemical
+reduces	B-Disease
+frontal	I-Disease
+lobe	I-Disease
+oxygenation	I-Disease
+following	O
+anesthesia	O
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Vasopressor	O
+agents	O
+are	O
+used	O
+to	O
+correct	O
+anesthesia	O
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+We	O
+describe	O
+the	O
+effect	O
+of	O
+phenylephrine	B-Chemical
+and	O
+ephedrine	B-Chemical
+on	O
+frontal	O
+lobe	O
+oxygenation	O
+(	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+)	O
+following	O
+anesthesia	O
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+METHODS	O
+:	O
+Following	O
+induction	O
+of	O
+anesthesia	O
+by	O
+fentanyl	B-Chemical
+(	O
+0	O
+.	O
+15	O
+mg	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+)	O
+and	O
+propofol	B-Chemical
+(	O
+2	O
+.	O
+0	O
+mg	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+)	O
+,	O
+13	O
+patients	O
+received	O
+phenylephrine	B-Chemical
+(	O
+0	O
+.	O
+1	O
+mg	O
+iv	O
+)	O
+and	O
+12	O
+patients	O
+received	O
+ephedrine	B-Chemical
+(	O
+10	O
+mg	O
+iv	O
+)	O
+to	O
+restore	O
+mean	O
+arterial	O
+pressure	O
+(	O
+MAP	O
+)	O
+.	O
+
+Heart	O
+rate	O
+(	O
+HR	O
+)	O
+,	O
+MAP	O
+,	O
+stroke	B-Disease
+volume	O
+(	O
+SV	O
+)	O
+,	O
+cardiac	O
+output	O
+(	O
+CO	O
+)	O
+,	O
+and	O
+frontal	O
+lobe	O
+oxygenation	O
+(	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+)	O
+were	O
+registered	O
+.	O
+
+RESULTS	O
+:	O
+Induction	O
+of	O
+anesthesia	O
+was	O
+followed	O
+by	O
+a	B-Disease
+decrease	I-Disease
+in	I-Disease
+MAP	I-Disease
+,	I-Disease
+HR	I-Disease
+,	I-Disease
+SV	I-Disease
+,	I-Disease
+and	I-Disease
+CO	I-Disease
+concomitant	O
+with	O
+an	O
+elevation	O
+in	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+.	O
+
+After	O
+administration	O
+of	O
+phenylephrine	B-Chemical
+,	O
+MAP	O
+increased	O
+(	O
+51	O
++	O
+/	O
+-	O
+12	O
+to	O
+81	O
++	O
+/	O
+-	O
+13	O
+mmHg	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+;	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+.	O
+
+However	O
+,	O
+a	O
+14	O
+%	O
+(	O
+from	O
+70	O
++	O
+/	O
+-	O
+8	O
+%	O
+to	O
+60	O
++	O
+/	O
+-	O
+7	O
+%	O
+)	O
+reduction	O
+in	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+followed	O
+with	O
+no	O
+change	O
+in	O
+CO	O
+(	O
+3	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+to	O
+3	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+9	O
+l	O
+min	O
+(	O
+-	O
+1	O
+)	O
+)	O
+.	O
+
+The	O
+administration	O
+of	O
+ephedrine	B-Chemical
+led	O
+to	O
+a	O
+similar	O
+increase	O
+in	O
+MAP	O
+(	O
+53	O
++	O
+/	O
+-	O
+9	O
+to	O
+79	O
++	O
+/	O
+-	O
+8	O
+mmHg	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+restored	O
+CO	O
+(	O
+3	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+to	O
+5	O
+.	O
+0	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+l	O
+min	O
+(	O
+-	O
+1	O
+)	O
+)	O
+,	O
+and	O
+preserved	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+utilization	O
+of	O
+phenylephrine	B-Chemical
+to	O
+correct	O
+hypotension	B-Disease
+induced	O
+by	O
+anesthesia	O
+has	O
+a	O
+negative	O
+impact	O
+on	O
+S	O
+(	O
+c	O
+)	O
+O	O
+(	O
+2	O
+)	O
+while	O
+ephedrine	B-Chemical
+maintains	O
+frontal	O
+lobe	O
+oxygenation	O
+potentially	O
+related	O
+to	O
+an	O
+increase	O
+in	O
+CO	O
+.	O
+
+Prolonged	O
+elevation	O
+of	O
+plasma	O
+argatroban	B-Chemical
+in	O
+a	O
+cardiac	O
+transplant	O
+patient	O
+with	O
+a	O
+suspected	O
+history	O
+of	O
+heparin	B-Chemical
+-	O
+induced	O
+thrombocytopenia	B-Disease
+with	O
+thrombosis	B-Disease
+.	O
+
+BACKGROUND	O
+:	O
+Direct	O
+thrombin	O
+inhibitors	O
+(	O
+DTIs	O
+)	O
+provide	O
+an	O
+alternative	O
+method	O
+of	O
+anticoagulation	O
+for	O
+patients	O
+with	O
+a	O
+history	O
+of	O
+heparin	B-Chemical
+-	O
+induced	O
+thrombocytopenia	B-Disease
+(	O
+HIT	B-Disease
+)	O
+or	O
+HIT	B-Disease
+with	O
+thrombosis	B-Disease
+(	O
+HITT	B-Disease
+)	O
+undergoing	O
+cardiopulmonary	O
+bypass	O
+(	O
+CPB	O
+)	O
+.	O
+
+In	O
+the	O
+following	O
+report	O
+,	O
+a	O
+65	O
+-	O
+year	O
+-	O
+old	O
+critically	B-Disease
+ill	I-Disease
+patient	O
+with	O
+a	O
+suspected	O
+history	O
+of	O
+HITT	B-Disease
+was	O
+administered	O
+argatroban	B-Chemical
+for	O
+anticoagulation	O
+on	O
+bypass	O
+during	O
+heart	O
+transplantation	O
+.	O
+
+The	O
+patient	O
+required	O
+massive	O
+transfusion	O
+support	O
+(	O
+55	O
+units	O
+of	O
+red	O
+blood	O
+cells	O
+,	O
+42	O
+units	O
+of	O
+fresh	O
+-	O
+frozen	O
+plasma	O
+,	O
+40	O
+units	O
+of	O
+cryoprecipitate	O
+,	O
+40	O
+units	O
+of	O
+platelets	O
+,	O
+and	O
+three	O
+doses	O
+of	O
+recombinant	O
+Factor	O
+VIIa	O
+)	O
+for	O
+severe	O
+intraoperative	B-Disease
+and	I-Disease
+postoperative	I-Disease
+bleeding	I-Disease
+.	O
+
+STUDY	O
+DESIGN	O
+AND	O
+METHODS	O
+:	O
+Plasma	O
+samples	O
+from	O
+before	O
+and	O
+after	O
+CPB	O
+were	O
+analyzed	O
+postoperatively	O
+for	O
+argatroban	B-Chemical
+concentration	O
+using	O
+a	O
+modified	O
+ecarin	O
+clotting	O
+time	O
+(	O
+ECT	O
+)	O
+assay	O
+.	O
+
+RESULTS	O
+:	O
+Unexpectedly	O
+high	O
+concentrations	O
+of	O
+argatroban	B-Chemical
+were	O
+measured	O
+in	O
+these	O
+samples	O
+(	O
+range	O
+,	O
+0	O
+-	O
+32	O
+microg	O
+/	O
+mL	O
+)	O
+,	O
+and	O
+a	O
+prolonged	O
+plasma	O
+argatroban	B-Chemical
+half	O
+life	O
+(	O
+t	O
+(	O
+1	O
+/	O
+2	O
+)	O
+)	O
+of	O
+514	O
+minutes	O
+was	O
+observed	O
+(	O
+published	O
+elimination	O
+t	O
+(	O
+1	O
+/	O
+2	O
+)	O
+is	O
+39	O
+-	O
+51	O
+minutes	O
+[	O
+<	O
+or	O
+=	O
+181	O
+minutes	O
+with	O
+hepatic	B-Disease
+impairment	I-Disease
+]	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Correlation	O
+of	O
+plasma	O
+argatroban	B-Chemical
+concentration	O
+versus	O
+the	O
+patient	O
+'	O
+s	O
+coagulation	O
+variables	O
+and	O
+clinical	O
+course	O
+suggest	O
+that	O
+prolonged	O
+elevated	O
+levels	O
+of	O
+plasma	O
+argatroban	B-Chemical
+may	O
+have	O
+contributed	O
+to	O
+the	O
+patient	O
+'	O
+s	O
+extended	O
+coagulopathy	B-Disease
+.	O
+
+Because	O
+DTIs	O
+do	O
+not	O
+have	O
+reversal	O
+agents	O
+,	O
+surgical	O
+teams	O
+and	O
+transfusion	O
+services	O
+should	O
+remain	O
+aware	O
+of	O
+the	O
+possibility	O
+of	O
+massive	O
+transfusion	O
+events	O
+during	O
+anticoagulation	O
+with	O
+these	O
+agents	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+report	O
+to	O
+measure	O
+plasma	O
+argatroban	B-Chemical
+concentration	O
+in	O
+the	O
+context	O
+of	O
+CPB	O
+and	O
+extended	O
+coagulopathy	B-Disease
+.	O
+
+The	O
+effects	O
+of	O
+the	O
+adjunctive	O
+bupropion	B-Chemical
+on	O
+male	O
+sexual	B-Disease
+dysfunction	I-Disease
+induced	O
+by	O
+a	O
+selective	B-Chemical
+serotonin	I-Chemical
+reuptake	I-Chemical
+inhibitor	I-Chemical
+:	O
+a	O
+double	O
+-	O
+blind	O
+placebo	O
+-	O
+controlled	O
+and	O
+randomized	O
+study	O
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+determine	O
+the	O
+safety	O
+and	O
+efficacy	O
+of	O
+adjunctive	O
+bupropion	B-Chemical
+sustained	O
+-	O
+release	O
+(	O
+SR	O
+)	O
+on	O
+male	O
+sexual	B-Disease
+dysfunction	I-Disease
+(	O
+SD	B-Disease
+)	O
+induced	O
+by	O
+a	O
+selective	B-Chemical
+serotonin	I-Chemical
+reuptake	I-Chemical
+inhibitor	I-Chemical
+(	O
+SSRI	B-Chemical
+)	O
+,	O
+as	O
+SD	B-Disease
+is	O
+a	O
+common	O
+side	O
+-	O
+effect	O
+of	O
+SSRIs	B-Chemical
+and	O
+the	O
+most	O
+effective	O
+treatments	O
+have	O
+yet	O
+to	O
+be	O
+determined	O
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+The	O
+randomized	O
+sample	O
+consisted	O
+of	O
+234	O
+euthymic	O
+men	O
+who	O
+were	O
+receiving	O
+some	O
+type	O
+of	O
+SSRI	B-Chemical
+.	O
+
+The	O
+men	O
+were	O
+randomly	O
+assigned	O
+to	O
+bupropion	B-Chemical
+SR	O
+(	O
+150	O
+mg	O
+twice	O
+daily	O
+,	O
+117	O
+)	O
+or	O
+placebo	O
+(	O
+twice	O
+daily	O
+,	O
+117	O
+)	O
+for	O
+12	O
+weeks	O
+.	O
+
+Efficacy	O
+was	O
+evaluated	O
+using	O
+the	O
+Clinical	O
+Global	O
+Impression	O
+-	O
+Sexual	O
+Function	O
+(	O
+CGI	O
+-	O
+SF	O
+;	O
+the	O
+primary	O
+outcome	O
+measure	O
+)	O
+,	O
+the	O
+International	O
+Index	O
+of	O
+Erectile	O
+Function	O
+(	O
+IIEF	O
+)	O
+,	O
+Arizona	O
+Sexual	O
+Experience	O
+Scale	O
+(	O
+ASEX	O
+)	O
+,	O
+and	O
+Erectile	B-Disease
+Dysfunction	I-Disease
+Inventory	O
+of	O
+Treatment	O
+Satisfaction	O
+(	O
+EDITS	O
+)	O
+(	O
+secondary	O
+outcome	O
+measures	O
+)	O
+.	O
+
+Participants	O
+were	O
+followed	O
+biweekly	O
+during	O
+study	O
+period	O
+.	O
+
+RESULTS	O
+:	O
+After	O
+12	O
+weeks	O
+of	O
+treatment	O
+,	O
+the	O
+mean	O
+(	O
+sd	O
+)	O
+scores	O
+for	O
+CGI	O
+-	O
+SF	O
+were	O
+significantly	O
+lower	O
+,	O
+i	O
+.	O
+e	O
+.	O
+better	O
+,	O
+in	O
+patients	O
+on	O
+bupropion	B-Chemical
+SR	O
+,	O
+at	O
+2	O
+.	O
+4	O
+(	O
+1	O
+.	O
+2	O
+)	O
+,	O
+than	O
+in	O
+the	O
+placebo	O
+group	O
+,	O
+at	O
+3	O
+.	O
+9	O
+(	O
+1	O
+.	O
+1	O
+)	O
+(	O
+P	O
+=	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Men	O
+who	O
+received	O
+bupropion	B-Chemical
+had	O
+a	O
+significant	O
+increase	O
+in	O
+the	O
+total	O
+IIEF	O
+score	O
+(	O
+54	O
+.	O
+4	O
+%	O
+vs	O
+1	O
+.	O
+2	O
+%	O
+;	O
+P	O
+=	O
+0	O
+.	O
+003	O
+)	O
+,	O
+and	O
+in	O
+the	O
+five	O
+different	O
+domains	O
+of	O
+the	O
+IIEF	O
+.	O
+
+Total	O
+ASEX	O
+scores	O
+were	O
+significantly	O
+lower	O
+,	O
+i	O
+.	O
+e	O
+.	O
+better	O
+,	O
+among	O
+men	O
+who	O
+received	O
+bupropion	B-Chemical
+than	O
+placebo	O
+,	O
+at	O
+15	O
+.	O
+5	O
+(	O
+4	O
+.	O
+3	O
+)	O
+vs	O
+21	O
+.	O
+5	O
+(	O
+4	O
+.	O
+7	O
+)	O
+(	O
+P	O
+=	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+The	O
+EDITS	O
+scores	O
+were	O
+67	O
+.	O
+4	O
+(	O
+10	O
+.	O
+2	O
+)	O
+for	O
+the	O
+bupropion	B-Chemical
+and	O
+36	O
+.	O
+3	O
+(	O
+11	O
+.	O
+7	O
+)	O
+for	O
+the	O
+placebo	O
+group	O
+(	O
+P	O
+=	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+The	O
+ASEX	O
+score	O
+and	O
+CGI	O
+-	O
+SF	O
+score	O
+were	O
+correlated	O
+(	O
+P	O
+=	O
+0	O
+.	O
+003	O
+)	O
+.	O
+
+In	O
+linear	O
+regression	O
+analyses	O
+the	O
+CGI	O
+-	O
+SF	O
+score	O
+was	O
+not	O
+affected	O
+significantly	O
+by	O
+the	O
+duration	O
+of	O
+SD	B-Disease
+,	O
+type	O
+of	O
+SSRI	B-Chemical
+used	O
+and	O
+age	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Bupropion	B-Chemical
+is	O
+an	O
+effective	O
+treatment	O
+for	O
+male	O
+SD	B-Disease
+induced	O
+by	O
+SSRIs	B-Chemical
+.	O
+
+These	O
+results	O
+provide	O
+empirical	O
+support	O
+for	O
+conducting	O
+a	O
+further	O
+study	O
+of	O
+bupropion	B-Chemical
+.	O
+
+Prevention	O
+of	O
+seizures	B-Disease
+and	O
+reorganization	O
+of	O
+hippocampal	O
+functions	O
+by	O
+transplantation	O
+of	O
+bone	O
+marrow	O
+cells	O
+in	O
+the	O
+acute	O
+phase	O
+of	O
+experimental	O
+epilepsy	B-Disease
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+investigated	O
+the	O
+therapeutic	O
+potential	O
+of	O
+bone	O
+marrow	O
+mononuclear	O
+cells	O
+(	O
+BMCs	O
+)	O
+in	O
+a	O
+model	O
+of	O
+epilepsy	B-Disease
+induced	O
+by	O
+pilocarpine	B-Chemical
+in	O
+rats	O
+.	O
+
+BMCs	O
+obtained	O
+from	O
+green	O
+fluorescent	O
+protein	O
+(	O
+GFP	O
+)	O
+transgenic	O
+mice	O
+or	O
+rats	O
+were	O
+transplanted	O
+intravenously	O
+after	O
+induction	O
+of	O
+status	B-Disease
+epilepticus	I-Disease
+(	O
+SE	B-Disease
+)	O
+.	O
+
+Spontaneous	B-Disease
+recurrent	I-Disease
+seizures	I-Disease
+(	O
+SRS	B-Disease
+)	O
+were	O
+monitored	O
+using	O
+Racine	O
+'	O
+s	O
+seizure	B-Disease
+severity	O
+scale	O
+.	O
+
+All	O
+of	O
+the	O
+rats	O
+in	O
+the	O
+saline	O
+-	O
+treated	O
+epileptic	B-Disease
+control	O
+group	O
+developed	O
+SRS	B-Disease
+,	O
+whereas	O
+none	O
+of	O
+the	O
+BMC	O
+-	O
+treated	O
+epileptic	B-Disease
+animals	O
+had	O
+seizures	B-Disease
+in	O
+the	O
+short	O
+term	O
+(	O
+15	O
+days	O
+after	O
+transplantation	O
+)	O
+,	O
+regardless	O
+of	O
+the	O
+BMC	O
+source	O
+.	O
+
+Over	O
+the	O
+long	O
+-	O
+term	O
+chronic	O
+phase	O
+(	O
+120	O
+days	O
+after	O
+transplantation	O
+)	O
+,	O
+only	O
+25	O
+%	O
+of	O
+BMC	O
+-	O
+treated	O
+epileptic	B-Disease
+animals	O
+had	O
+seizures	B-Disease
+,	O
+but	O
+with	O
+a	O
+lower	O
+frequency	O
+and	O
+duration	O
+compared	O
+to	O
+the	O
+epileptic	B-Disease
+control	O
+group	O
+.	O
+
+The	O
+density	O
+of	O
+hippocampal	O
+neurons	O
+in	O
+the	O
+brains	O
+of	O
+animals	O
+treated	O
+with	O
+BMCs	O
+was	O
+markedly	O
+preserved	O
+.	O
+
+At	O
+hippocampal	O
+Schaeffer	O
+collateral	O
+-	O
+CA1	O
+synapses	O
+,	O
+long	O
+-	O
+term	O
+potentiation	O
+was	O
+preserved	O
+in	O
+BMC	O
+-	O
+transplanted	O
+rats	O
+compared	O
+to	O
+epileptic	B-Disease
+controls	O
+.	O
+
+The	O
+donor	O
+-	O
+derived	O
+GFP	O
+(	O
++	O
+)	O
+cells	O
+were	O
+rarely	O
+found	O
+in	O
+the	O
+brains	O
+of	O
+transplanted	O
+epileptic	B-Disease
+rats	O
+.	O
+
+In	O
+conclusion	O
+,	O
+treatment	O
+with	O
+BMCs	O
+can	O
+prevent	O
+the	O
+development	O
+of	O
+chronic	O
+seizures	B-Disease
+,	O
+reduce	O
+neuronal	B-Disease
+loss	I-Disease
+,	O
+and	O
+influence	O
+the	O
+reorganization	O
+of	O
+the	O
+hippocampal	O
+neuronal	O
+network	O
+.	O
+
+Normalizing	O
+effects	O
+of	O
+modafinil	B-Chemical
+on	O
+sleep	O
+in	O
+chronic	O
+cocaine	B-Chemical
+users	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+purpose	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+effect	O
+of	O
+morning	O
+-	O
+dosed	O
+modafinil	B-Chemical
+on	O
+sleep	O
+and	O
+daytime	B-Disease
+sleepiness	I-Disease
+in	O
+chronic	O
+cocaine	B-Chemical
+users	O
+.	O
+
+METHOD	O
+:	O
+Twenty	O
+cocaine	B-Chemical
+-	O
+dependent	O
+participants	O
+were	O
+randomly	O
+assigned	O
+to	O
+receive	O
+modafinil	B-Chemical
+,	O
+400	O
+mg	O
+(	O
+N	O
+=	O
+10	O
+)	O
+,	O
+or	O
+placebo	O
+(	O
+N	O
+=	O
+10	O
+)	O
+every	O
+morning	O
+at	O
+7	O
+:	O
+30	O
+a	O
+.	O
+m	O
+.	O
+for	O
+16	O
+days	O
+in	O
+an	O
+inpatient	O
+,	O
+double	O
+-	O
+blind	O
+randomized	O
+trial	O
+.	O
+
+Participants	O
+underwent	O
+polysomnographic	O
+sleep	O
+recordings	O
+on	O
+days	O
+1	O
+to	O
+3	O
+,	O
+7	O
+to	O
+9	O
+,	O
+and	O
+14	O
+to	O
+16	O
+(	O
+first	O
+,	O
+second	O
+,	O
+and	O
+third	O
+weeks	O
+of	O
+abstinence	O
+)	O
+.	O
+
+The	O
+Multiple	O
+Sleep	O
+Latency	O
+Test	O
+was	O
+performed	O
+at	O
+11	O
+:	O
+30	O
+a	O
+.	O
+m	O
+.	O
+,	O
+2	O
+:	O
+00	O
+p	O
+.	O
+m	O
+.	O
+,	O
+and	O
+4	O
+:	O
+30	O
+p	O
+.	O
+m	O
+.	O
+on	O
+days	O
+2	O
+,	O
+8	O
+,	O
+and	O
+15	O
+.	O
+
+For	O
+comparison	O
+of	O
+sleep	O
+architecture	O
+variables	O
+,	O
+12	O
+healthy	O
+comparison	O
+participants	O
+underwent	O
+a	O
+single	O
+night	O
+of	O
+experimental	O
+polysomnography	O
+that	O
+followed	O
+1	O
+night	O
+of	O
+accommodation	O
+polysomnography	O
+.	O
+
+RESULTS	O
+:	O
+Progressive	O
+abstinence	O
+from	O
+cocaine	B-Chemical
+was	O
+associated	O
+with	O
+worsening	O
+of	O
+all	O
+measured	O
+polysomnographic	O
+sleep	O
+outcomes	O
+.	O
+
+Compared	O
+with	O
+placebo	O
+,	O
+modafinil	B-Chemical
+decreased	O
+nighttime	O
+sleep	O
+latency	O
+and	O
+increased	O
+slow	O
+-	O
+wave	O
+sleep	O
+time	O
+in	O
+cocaine	B-Chemical
+-	O
+dependent	O
+participants	O
+.	O
+
+The	O
+effect	O
+of	O
+modafinil	B-Chemical
+interacted	O
+with	O
+the	O
+abstinence	O
+week	O
+and	O
+was	O
+associated	O
+with	O
+longer	O
+total	O
+sleep	O
+time	O
+and	O
+shorter	O
+REM	O
+sleep	O
+latency	O
+in	O
+the	O
+third	O
+week	O
+of	O
+abstinence	O
+.	O
+
+Comparison	O
+of	O
+slow	O
+-	O
+wave	O
+sleep	O
+time	O
+,	O
+total	O
+sleep	O
+time	O
+,	O
+and	O
+sleep	O
+latency	O
+in	O
+cocaine	B-Chemical
+-	O
+dependent	O
+and	O
+healthy	O
+participants	O
+revealed	O
+a	O
+normalizing	O
+effect	O
+of	O
+modafinil	B-Chemical
+in	O
+cocaine	B-Chemical
+-	O
+dependent	O
+participants	O
+.	O
+
+Modafinil	B-Chemical
+was	O
+associated	O
+with	O
+increased	O
+daytime	O
+sleep	O
+latency	O
+,	O
+as	O
+measured	O
+by	O
+the	O
+Multiple	O
+Sleep	O
+Latency	O
+Test	O
+,	O
+and	O
+a	O
+nearly	O
+significant	O
+decrease	O
+in	O
+subjective	O
+daytime	B-Disease
+sleepiness	I-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+Morning	O
+-	O
+dosed	O
+modafinil	B-Chemical
+promotes	O
+nocturnal	O
+sleep	O
+,	O
+normalizes	O
+sleep	O
+architecture	O
+,	O
+and	O
+decreases	O
+daytime	B-Disease
+sleepiness	I-Disease
+in	O
+abstinent	O
+cocaine	B-Chemical
+users	O
+.	O
+
+These	O
+effects	O
+may	O
+be	O
+relevant	O
+in	O
+the	O
+treatment	O
+of	O
+cocaine	B-Chemical
+dependence	O
+.	O
+
+Safety	O
+of	O
+transesophageal	O
+echocardiography	O
+in	O
+adults	O
+:	O
+study	O
+in	O
+a	O
+multidisciplinary	O
+hospital	O
+.	O
+
+BACKGROUND	O
+:	O
+TEE	O
+is	O
+a	O
+semi	O
+-	O
+invasive	O
+tool	O
+broadly	O
+used	O
+and	O
+its	O
+utilization	O
+associated	O
+to	O
+sedatives	O
+drugs	O
+might	O
+to	O
+affect	O
+the	O
+procedure	O
+safety	O
+.	O
+
+OBJECTIVE	O
+:	O
+to	O
+analyze	O
+aspects	O
+of	O
+TEE	O
+safety	O
+associated	O
+to	O
+the	O
+use	O
+of	O
+Midazolan	B-Chemical
+(	O
+MZ	B-Chemical
+)	O
+and	O
+Flumazenil	B-Chemical
+(	O
+FL	B-Chemical
+)	O
+and	O
+the	O
+influence	O
+of	O
+the	O
+clinical	O
+variables	O
+on	O
+the	O
+event	O
+rate	O
+.	O
+
+METHOD	O
+:	O
+prospective	O
+study	O
+with	O
+137	O
+patients	O
+that	O
+underwent	O
+TEE	O
+with	O
+MZ	B-Chemical
+associated	O
+to	O
+moderate	O
+sedation	O
+.	O
+
+We	O
+analyzed	O
+the	O
+following	O
+events	O
+:	O
+complications	O
+related	O
+with	O
+the	O
+topical	O
+anesthesia	O
+,	O
+with	O
+MZ	B-Chemical
+use	O
+and	O
+with	O
+the	O
+procedure	O
+.	O
+
+Uni	O
+-	O
+and	O
+multivariate	O
+analyses	O
+were	O
+used	O
+to	O
+test	O
+the	O
+influence	O
+of	O
+the	O
+clinical	O
+variables	O
+:	O
+age	O
+,	O
+sex	O
+,	O
+stroke	B-Disease
+,	O
+myocardiopathy	B-Disease
+(	O
+MP	B-Disease
+)	O
+,	O
+duration	O
+of	O
+the	O
+test	O
+,	O
+mitral	B-Disease
+regurgitation	I-Disease
+(	O
+MR	B-Disease
+)	O
+and	O
+the	O
+MZ	B-Chemical
+dose	O
+.	O
+
+RESULTS	O
+:	O
+All	O
+patients	O
+(	O
+65	O
++	O
+/	O
+-	O
+16	O
+yrs	O
+;	O
+58	O
+%	O
+males	O
+)	O
+finished	O
+the	O
+examination	O
+.	O
+
+The	O
+mean	O
+doses	O
+of	O
+MZ	B-Chemical
+and	O
+FL	B-Chemical
+were	O
+4	O
+.	O
+3	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+mg	O
+and	O
+0	O
+.	O
+28	O
++	O
+/	O
+-	O
+0	O
+.	O
+2	O
+mg	O
+,	O
+respectively	O
+.	O
+
+The	O
+duration	O
+of	O
+the	O
+examination	O
+and	O
+the	O
+mean	O
+ejection	O
+fraction	O
+(	O
+EF	O
+)	O
+were	O
+16	O
+.	O
+4	O
++	O
+/	O
+-	O
+6	O
+.	O
+1	O
+minutes	O
+and	O
+60	O
++	O
+/	O
+-	O
+9	O
+%	O
+,	O
+respectively	O
+.	O
+
+Mild	O
+hypoxia	B-Disease
+(	O
+SO2	O
+<	O
+90	O
+%	O
+)	O
+was	O
+the	O
+most	O
+common	O
+event	O
+(	O
+11	O
+patients	O
+)	O
+;	O
+3	O
+patients	O
+(	O
+2	O
+%	O
+)	O
+presented	O
+transient	O
+hypoxia	B-Disease
+due	O
+to	O
+upper	O
+airway	B-Disease
+obstruction	I-Disease
+by	O
+probe	O
+introduction	O
+and	O
+8	O
+(	O
+5	O
+.	O
+8	O
+%	O
+)	O
+due	O
+to	O
+hypoxia	B-Disease
+caused	O
+by	O
+MZ	B-Chemical
+use	O
+.	O
+
+Transient	O
+hypotension	B-Disease
+(	O
+SAP	O
+<	O
+90mmHg	O
+)	O
+occurred	O
+in	O
+1	O
+patient	O
+(	O
+0	O
+.	O
+7	O
+%	O
+)	O
+.	O
+
+The	O
+multivariate	O
+analysis	O
+showed	O
+that	O
+severe	O
+MR	B-Disease
+,	O
+MP	B-Disease
+(	O
+EF	O
+<	O
+45	O
+%	O
+)	O
+and	O
+high	O
+doses	O
+of	O
+MZ	B-Chemical
+(	O
+>	O
+5mg	O
+)	O
+were	O
+associated	O
+with	O
+events	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+The	O
+EF	O
+was	O
+40	O
+%	O
+,	O
+in	O
+the	O
+group	O
+with	O
+MP	B-Disease
+and	O
+44	O
+%	O
+in	O
+the	O
+group	O
+with	O
+severe	O
+MR	B-Disease
+and	O
+it	O
+can	O
+be	O
+a	O
+factor	O
+associated	O
+with	O
+clinical	O
+events	O
+in	O
+the	O
+last	O
+group	O
+.	O
+
+CONCLUSION	O
+:	O
+TEE	O
+with	O
+sedation	O
+presents	O
+a	O
+low	O
+rate	O
+of	O
+events	O
+.	O
+
+There	O
+were	O
+no	O
+severe	O
+events	O
+and	O
+there	O
+was	O
+no	O
+need	O
+to	O
+interrupt	O
+the	O
+examinations	O
+.	O
+
+Effect	O
+of	O
+direct	O
+intracoronary	O
+administration	O
+of	O
+methylergonovine	B-Chemical
+in	O
+patients	O
+with	O
+and	O
+without	O
+variant	B-Disease
+angina	I-Disease
+.	O
+
+The	O
+effects	O
+of	O
+intracoronary	O
+administration	O
+of	O
+methylergonovine	B-Chemical
+were	O
+studied	O
+in	O
+21	O
+patients	O
+with	O
+variant	B-Disease
+angina	I-Disease
+and	O
+22	O
+patients	O
+with	O
+atypical	O
+chest	B-Disease
+pain	I-Disease
+and	O
+in	O
+others	O
+without	O
+angina	B-Disease
+pectoris	I-Disease
+(	O
+control	O
+group	O
+)	O
+.	O
+
+Methylergonovine	B-Chemical
+was	O
+administered	O
+continuously	O
+at	O
+a	O
+rate	O
+of	O
+10	O
+micrograms	O
+/	O
+min	O
+up	O
+to	O
+50	O
+micrograms	O
+.	O
+
+In	O
+all	O
+patients	O
+with	O
+variant	B-Disease
+angina	I-Disease
+,	O
+coronary	B-Disease
+spasm	I-Disease
+was	O
+provoked	O
+at	O
+a	O
+mean	O
+dose	O
+of	O
+28	O
++	O
+/	O
+-	O
+13	O
+micrograms	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+.	O
+
+In	O
+the	O
+control	O
+group	O
+neither	O
+ischemic	O
+ST	O
+change	O
+nor	O
+localized	O
+spasm	B-Disease
+occurred	O
+.	O
+
+The	O
+basal	O
+tone	O
+of	O
+the	O
+right	O
+coronary	O
+artery	O
+was	O
+significantly	O
+lower	O
+than	O
+that	O
+of	O
+the	O
+left	O
+coronary	O
+artery	O
+.	O
+
+The	O
+percentage	O
+of	O
+vasoconstriction	O
+of	O
+the	O
+right	O
+coronary	O
+artery	O
+was	O
+significantly	O
+higher	O
+than	O
+that	O
+of	O
+the	O
+left	O
+coronary	O
+artery	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+spasm	B-Disease
+provocation	O
+tests	O
+,	O
+which	O
+use	O
+an	O
+intracoronary	O
+injection	O
+of	O
+a	O
+relatively	O
+low	O
+dose	O
+of	O
+methylergonovine	B-Chemical
+,	O
+have	O
+a	O
+high	O
+sensitivity	O
+in	O
+variant	B-Disease
+angina	I-Disease
+and	O
+the	O
+vasoreactivity	O
+of	O
+the	O
+right	O
+coronary	O
+artery	O
+may	O
+be	O
+greater	O
+than	O
+that	O
+of	O
+the	O
+other	O
+coronary	O
+arteries	O
+.	O
+
+Oral	O
+manifestations	O
+of	O
+"	O
+meth	B-Disease
+mouth	I-Disease
+"	O
+:	O
+a	O
+case	O
+report	O
+.	O
+
+AIM	O
+:	O
+The	O
+aim	O
+of	O
+the	O
+documentation	O
+of	O
+this	O
+clinical	O
+case	O
+is	O
+to	O
+make	O
+clinicians	O
+aware	O
+of	O
+"	O
+meth	B-Disease
+mouth	I-Disease
+"	O
+and	O
+the	O
+medical	O
+risks	O
+associated	O
+with	O
+this	O
+serious	O
+condition	O
+.	O
+
+BACKGROUND	O
+:	O
+Methamphetamine	B-Chemical
+is	O
+a	O
+very	O
+addictive	O
+,	O
+powerful	O
+stimulant	O
+that	O
+increases	O
+wakefulness	O
+and	O
+physical	O
+activity	O
+and	O
+can	O
+produce	O
+other	O
+effects	O
+such	O
+as	O
+cardiac	B-Disease
+dysrhythmias	I-Disease
+,	O
+hypertension	B-Disease
+,	O
+hallucinations	B-Disease
+,	O
+and	O
+violent	B-Disease
+behavior	I-Disease
+.	O
+
+Dental	O
+patients	O
+abusing	O
+methamphetamine	B-Chemical
+can	O
+present	O
+with	O
+poor	O
+oral	O
+hygiene	O
+,	O
+xerostomia	B-Disease
+,	O
+rampant	O
+caries	B-Disease
+(	O
+"	O
+meth	B-Disease
+mouth	I-Disease
+"	O
+)	O
+,	O
+and	O
+excessive	O
+tooth	B-Disease
+wear	I-Disease
+.	O
+
+Oral	O
+rehabilitation	O
+of	O
+patients	O
+using	O
+methamphetamine	B-Chemical
+can	O
+be	O
+challenging	O
+.	O
+
+CASE	O
+DESCRIPTION	O
+:	O
+A	O
+30	O
+-	O
+year	O
+-	O
+old	O
+Caucasian	O
+woman	O
+presented	O
+with	O
+dental	O
+pain	B-Disease
+,	O
+bad	B-Disease
+breath	I-Disease
+,	O
+and	O
+self	O
+-	O
+reported	O
+poor	O
+esthetics	O
+.	O
+
+A	O
+comprehensive	O
+examination	O
+including	O
+her	O
+medical	O
+history	O
+,	O
+panoramic	O
+radiograph	O
+,	O
+and	O
+intraoral	O
+examination	O
+revealed	O
+19	O
+carious	B-Disease
+lesions	I-Disease
+,	O
+which	O
+is	O
+not	O
+very	O
+common	O
+for	O
+a	O
+healthy	O
+adult	O
+.	O
+
+She	O
+reported	O
+her	O
+use	O
+of	O
+methamphetamine	B-Chemical
+for	O
+five	O
+years	O
+and	O
+had	O
+not	O
+experienced	O
+any	O
+major	O
+carious	B-Disease
+episodes	I-Disease
+before	O
+she	O
+started	O
+using	O
+the	O
+drug	O
+.	O
+
+SUMMARY	O
+:	O
+The	O
+patient	O
+'	O
+s	O
+medical	O
+and	O
+dental	O
+histories	O
+along	O
+with	O
+radiographic	O
+and	O
+clinical	O
+findings	O
+lead	O
+to	O
+a	O
+diagnosis	O
+of	O
+"	O
+meth	B-Disease
+mouth	I-Disease
+.	O
+"	O
+Although	O
+three	O
+different	O
+dental	O
+treatment	O
+modalities	O
+(	O
+either	O
+conventional	O
+or	O
+implant	O
+-	O
+supported	O
+)	O
+have	O
+been	O
+offered	O
+to	O
+the	O
+patient	O
+since	O
+August	O
+2007	O
+,	O
+the	O
+patient	O
+has	O
+yet	O
+to	O
+initiate	O
+any	O
+treatment	O
+.	O
+
+CLINICAL	O
+SIGNIFICANCE	O
+:	O
+This	O
+clinical	O
+case	O
+showing	O
+oral	O
+manifestations	O
+of	O
+meth	B-Disease
+mouth	I-Disease
+was	O
+presented	O
+to	O
+help	O
+dental	O
+practitioners	O
+recognize	O
+and	O
+manage	O
+patients	O
+who	O
+may	O
+be	O
+abusing	O
+methamphetamines	B-Chemical
+.	O
+
+Dental	O
+practitioners	O
+also	O
+may	O
+be	O
+skeptical	O
+about	O
+the	O
+reliability	O
+of	O
+appointment	O
+keeping	O
+by	O
+these	O
+patients	O
+,	O
+as	O
+they	O
+frequently	O
+miss	O
+their	O
+appointments	O
+without	O
+reasonable	O
+justification	O
+.	O
+
+Antituberculosis	B-Chemical
+therapy	O
+-	O
+induced	O
+acute	B-Disease
+liver	I-Disease
+failure	I-Disease
+:	O
+magnitude	O
+,	O
+profile	O
+,	O
+prognosis	O
+,	O
+and	O
+predictors	O
+of	O
+outcome	O
+.	O
+
+Antituberculosis	B-Chemical
+therapy	O
+(	O
+ATT	O
+)	O
+-	O
+associated	O
+acute	B-Disease
+liver	I-Disease
+failure	I-Disease
+(	O
+ATT	O
+-	O
+ALF	B-Disease
+)	O
+is	O
+the	O
+commonest	O
+drug	O
+-	O
+induced	O
+ALF	B-Disease
+in	O
+South	O
+Asia	O
+.	O
+
+Prospective	O
+studies	O
+on	O
+ATT	O
+-	O
+ALF	B-Disease
+are	O
+lacking	O
+.	O
+
+The	O
+current	O
+study	O
+prospectively	O
+evaluated	O
+the	O
+magnitude	O
+,	O
+clinical	O
+course	O
+,	O
+outcome	O
+,	O
+and	O
+prognostic	O
+factors	O
+in	O
+ATT	O
+-	O
+ALF	B-Disease
+.	O
+
+From	O
+January	O
+1986	O
+to	O
+January	O
+2009	O
+,	O
+1223	O
+consecutive	O
+ALF	B-Disease
+patients	O
+were	O
+evaluated	O
+:	O
+ATT	O
+alone	O
+was	O
+the	O
+cause	O
+in	O
+70	O
+(	O
+5	O
+.	O
+7	O
+%	O
+)	O
+patients	O
+.	O
+
+Another	O
+15	O
+(	O
+1	O
+.	O
+2	O
+%	O
+)	O
+had	O
+ATT	O
+and	O
+simultaneous	O
+hepatitis	B-Disease
+virus	I-Disease
+infection	I-Disease
+.	O
+
+In	O
+44	O
+(	O
+62	O
+.	O
+8	O
+%	O
+)	O
+patients	O
+,	O
+ATT	O
+was	O
+prescribed	O
+empirically	O
+without	O
+definitive	O
+evidence	O
+of	O
+tuberculosis	B-Disease
+.	O
+
+ATT	O
+-	O
+ALF	B-Disease
+patients	O
+were	O
+younger	O
+(	O
+32	O
+.	O
+87	O
+[	O
++	O
+/	O
+-	O
+15	O
+.	O
+8	O
+]	O
+years	O
+)	O
+,	O
+and	O
+49	O
+(	O
+70	O
+%	O
+)	O
+of	O
+them	O
+were	O
+women	O
+.	O
+
+Most	O
+had	O
+hyperacute	O
+presentation	O
+;	O
+the	O
+median	O
+icterus	B-Disease
+encephalopathy	B-Disease
+interval	O
+was	O
+4	O
+.	O
+5	O
+(	O
+0	O
+-	O
+30	O
+)	O
+days	O
+.	O
+
+The	O
+median	O
+duration	O
+of	O
+ATT	O
+before	O
+ALF	B-Disease
+was	O
+30	O
+(	O
+7	O
+-	O
+350	O
+)	O
+days	O
+.	O
+
+At	O
+presentation	O
+,	O
+advanced	O
+encephalopathy	B-Disease
+and	O
+cerebral	B-Disease
+edema	I-Disease
+were	O
+present	O
+in	O
+51	O
+(	O
+76	O
+%	O
+)	O
+and	O
+29	O
+(	O
+41	O
+.	O
+4	O
+%	O
+)	O
+patients	O
+,	O
+respectively	O
+.	O
+
+Gastrointestinal	B-Disease
+bleed	I-Disease
+,	O
+seizures	B-Disease
+,	O
+infection	B-Disease
+,	O
+and	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+were	O
+documented	O
+in	O
+seven	O
+(	O
+10	O
+%	O
+)	O
+,	O
+five	O
+(	O
+7	O
+.	O
+1	O
+%	O
+)	O
+,	O
+26	O
+(	O
+37	O
+.	O
+1	O
+%	O
+)	O
+,	O
+and	O
+seven	O
+(	O
+10	O
+%	O
+)	O
+patients	O
+,	O
+respectively	O
+.	O
+
+Compared	O
+with	O
+hepatitis	B-Disease
+E	I-Disease
+virus	O
+(	O
+HEV	O
+)	O
+and	O
+non	O
+-	O
+A	O
+non	O
+-	O
+E	O
+-	O
+induced	O
+ALF	B-Disease
+,	O
+ATT	O
+-	O
+ALF	B-Disease
+patients	O
+had	O
+nearly	O
+similar	O
+presentations	O
+except	O
+for	O
+older	O
+age	O
+and	O
+less	O
+elevation	O
+of	O
+liver	O
+enzymes	O
+.	O
+
+The	O
+mortality	O
+rate	O
+among	O
+patients	O
+with	O
+ATT	O
+-	O
+ALF	B-Disease
+was	O
+high	O
+(	O
+67	O
+.	O
+1	O
+%	O
+,	O
+n	O
+=	O
+47	O
+)	O
+,	O
+and	O
+only	O
+23	O
+(	O
+32	O
+.	O
+9	O
+%	O
+)	O
+patients	O
+recovered	O
+with	O
+medical	O
+treatment	O
+.	O
+
+In	O
+multivariate	O
+analysis	O
+,	O
+three	O
+factors	O
+independently	O
+predicted	O
+mortality	O
+:	O
+serum	O
+bilirubin	B-Chemical
+(	O
+>	O
+or	O
+=	O
+10	O
+.	O
+8	O
+mg	O
+/	O
+dL	O
+)	O
+,	O
+prothrombin	O
+time	O
+(	O
+PT	O
+)	O
+prolongation	O
+(	O
+>	O
+or	O
+=	O
+26	O
+seconds	O
+)	O
+,	O
+and	O
+grade	O
+III	O
+/	O
+IV	O
+encephalopathy	B-Disease
+at	O
+presentation	O
+.	O
+
+CONCLUSION	O
+:	O
+ATT	O
+-	O
+ALF	B-Disease
+constituted	O
+5	O
+.	O
+7	O
+%	O
+of	O
+ALF	B-Disease
+at	O
+our	O
+center	O
+and	O
+had	O
+a	O
+high	O
+mortality	O
+rate	O
+.	O
+
+Because	O
+the	O
+mortality	O
+rate	O
+is	O
+so	O
+high	O
+,	O
+determining	O
+which	O
+factors	O
+are	O
+predictors	O
+is	O
+less	O
+important	O
+.	O
+
+A	O
+high	O
+proportion	O
+of	O
+patients	O
+had	O
+consumed	O
+ATT	O
+empirically	O
+,	O
+which	O
+could	O
+have	O
+been	O
+prevented	O
+.	O
+
+Design	O
+and	O
+analysis	O
+of	O
+the	O
+HYPREN	O
+-	O
+trial	O
+:	O
+safety	O
+of	O
+enalapril	B-Chemical
+and	O
+prazosin	B-Chemical
+in	O
+the	O
+initial	O
+treatment	O
+phase	O
+of	O
+patients	O
+with	O
+congestive	B-Disease
+heart	I-Disease
+failure	I-Disease
+.	O
+
+Since	O
+the	O
+introduction	O
+of	O
+angiotensin	B-Chemical
+converting	I-Chemical
+enzyme	I-Chemical
+(	I-Chemical
+ACE	I-Chemical
+)	I-Chemical
+inhibitors	I-Chemical
+into	O
+the	O
+adjunctive	O
+treatment	O
+of	O
+patients	O
+with	O
+congestive	B-Disease
+heart	I-Disease
+failure	I-Disease
+,	O
+cases	O
+of	O
+severe	O
+hypotension	B-Disease
+,	O
+especially	O
+on	O
+the	O
+first	O
+day	O
+of	O
+treatment	O
+,	O
+have	O
+occasionally	O
+been	O
+reported	O
+.	O
+
+To	O
+assess	O
+the	O
+safety	O
+of	O
+the	O
+ACE	B-Chemical
+inhibitor	I-Chemical
+enalapril	B-Chemical
+a	O
+multicenter	O
+,	O
+randomized	O
+,	O
+prazosin	B-Chemical
+-	O
+controlled	O
+trial	O
+was	O
+designed	O
+that	O
+compared	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+symptomatic	O
+hypotension	B-Disease
+on	O
+the	O
+first	O
+day	O
+of	O
+treatment	O
+.	O
+
+Trial	O
+medication	O
+was	O
+2	O
+.	O
+5	O
+mg	O
+enalapril	B-Chemical
+or	O
+0	O
+.	O
+5	O
+prazosin	B-Chemical
+.	O
+
+Subjects	O
+were	O
+1210	O
+inpatients	O
+with	O
+New	O
+York	O
+Heart	O
+Association	O
+(	O
+NYHA	O
+)	O
+functional	O
+class	O
+II	O
+and	O
+III	O
+.	O
+
+Patients	O
+who	O
+received	O
+enalapril	B-Chemical
+experienced	O
+clinically	O
+and	O
+statistically	O
+significantly	O
+less	O
+symptomatic	O
+hypotension	B-Disease
+(	O
+5	O
+.	O
+2	O
+%	O
+)	O
+than	O
+the	O
+patients	O
+who	O
+received	O
+prazosin	B-Chemical
+(	O
+12	O
+.	O
+9	O
+%	O
+)	O
+.	O
+
+All	O
+patients	O
+recovered	O
+.	O
+
+It	O
+was	O
+concluded	O
+that	O
+treatment	O
+with	O
+enalapril	B-Chemical
+was	O
+well	O
+tolerated	O
+and	O
+it	O
+is	O
+,	O
+therefore	O
+,	O
+unreasonable	O
+to	O
+restrict	O
+the	O
+initiation	O
+of	O
+treatment	O
+with	O
+enalapril	B-Chemical
+to	O
+inpatients	O
+.	O
+
+Central	B-Disease
+nervous	I-Disease
+system	I-Disease
+complications	I-Disease
+during	O
+treatment	O
+of	O
+acute	B-Disease
+lymphoblastic	I-Disease
+leukemia	I-Disease
+in	O
+a	O
+single	O
+pediatric	O
+institution	O
+.	O
+
+Central	B-Disease
+nervous	I-Disease
+system	I-Disease
+(	I-Disease
+CNS	I-Disease
+)	I-Disease
+complications	I-Disease
+during	O
+treatment	O
+of	O
+childhood	O
+acute	B-Disease
+lymphoblastic	I-Disease
+leukemia	I-Disease
+(	O
+ALL	B-Disease
+)	O
+remain	O
+a	O
+challenging	O
+clinical	O
+problem	O
+.	O
+
+Outcome	O
+improvement	O
+with	O
+more	O
+intensive	O
+chemotherapy	O
+has	O
+significantly	O
+increased	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+adverse	O
+events	O
+.	O
+
+This	O
+study	O
+analyzed	O
+the	O
+incidence	O
+of	O
+neurological	B-Disease
+complications	I-Disease
+during	O
+ALL	B-Disease
+treatment	O
+in	O
+a	O
+single	O
+pediatric	O
+institution	O
+,	O
+focusing	O
+on	O
+clinical	O
+,	O
+radiological	O
+,	O
+and	O
+electrophysiological	O
+findings	O
+.	O
+
+Exclusion	O
+criteria	O
+included	O
+CNS	O
+leukemic	B-Disease
+infiltration	I-Disease
+at	O
+diagnosis	O
+,	O
+therapy	O
+-	O
+related	O
+peripheral	B-Disease
+neuropathy	I-Disease
+,	O
+late	O
+-	O
+onset	O
+encephalopathy	B-Disease
+,	O
+or	O
+long	O
+-	O
+term	O
+neurocognitive	B-Disease
+defects	I-Disease
+.	O
+
+During	O
+a	O
+9	O
+-	O
+year	O
+period	O
+,	O
+we	O
+retrospectively	O
+collected	O
+27	O
+neurological	O
+events	O
+(	O
+11	O
+%	O
+)	O
+in	O
+as	O
+many	O
+patients	O
+,	O
+from	O
+253	O
+children	O
+enrolled	O
+in	O
+the	O
+ALL	B-Disease
+front	O
+-	O
+line	O
+protocol	O
+.	O
+
+CNS	O
+complications	O
+included	O
+posterior	O
+reversible	O
+leukoencephalopathy	B-Disease
+syndrome	O
+(	O
+n	O
+=	O
+10	O
+)	O
+,	O
+stroke	B-Disease
+(	O
+n	O
+=	O
+5	O
+)	O
+,	O
+temporal	B-Disease
+lobe	I-Disease
+epilepsy	I-Disease
+(	O
+n	O
+=	O
+2	O
+)	O
+,	O
+high	O
+-	O
+dose	O
+methotrexate	B-Chemical
+toxicity	B-Disease
+(	O
+n	O
+=	O
+2	O
+)	O
+,	O
+syndrome	O
+of	O
+inappropriate	B-Disease
+antidiuretic	I-Disease
+hormone	I-Disease
+secretion	I-Disease
+(	O
+n	O
+=	O
+1	O
+)	O
+,	O
+and	O
+other	O
+unclassified	O
+events	O
+(	O
+n	O
+=	O
+7	O
+)	O
+.	O
+
+In	O
+conclusion	O
+,	O
+CNS	O
+complications	O
+are	O
+frequent	O
+events	O
+during	O
+ALL	B-Disease
+therapy	O
+,	O
+and	O
+require	O
+rapid	O
+detection	O
+and	O
+prompt	O
+treatment	O
+to	O
+limit	O
+permanent	O
+damage	O
+.	O
+
+Cocaine	B-Chemical
+causes	O
+memory	B-Disease
+and	I-Disease
+learning	I-Disease
+impairments	I-Disease
+in	O
+rats	O
+:	O
+involvement	O
+of	O
+nuclear	O
+factor	O
+kappa	O
+B	O
+and	O
+oxidative	O
+stress	O
+,	O
+and	O
+prevention	O
+by	O
+topiramate	B-Chemical
+.	O
+
+Different	O
+mechanisms	O
+have	O
+been	O
+suggested	O
+for	O
+cocaine	B-Chemical
+toxicity	B-Disease
+including	O
+an	O
+increase	O
+in	O
+oxidative	O
+stress	O
+but	O
+the	O
+association	O
+between	O
+oxidative	O
+status	O
+in	O
+the	O
+brain	O
+and	O
+cocaine	B-Chemical
+induced	O
+-	O
+behaviour	O
+is	O
+poorly	O
+understood	O
+.	O
+
+Nuclear	O
+factor	O
+kappa	O
+B	O
+(	O
+NFkappaB	O
+)	O
+is	O
+a	O
+sensor	O
+of	O
+oxidative	O
+stress	O
+and	O
+participates	O
+in	O
+memory	O
+formation	O
+that	O
+could	O
+be	O
+involved	O
+in	O
+drug	O
+toxicity	B-Disease
+and	O
+addiction	O
+mechanisms	O
+.	O
+
+Therefore	O
+NFkappaB	O
+activity	O
+,	O
+oxidative	O
+stress	O
+,	O
+neuronal	O
+nitric	B-Chemical
+oxide	I-Chemical
+synthase	O
+(	O
+nNOS	O
+)	O
+activity	O
+,	O
+spatial	O
+learning	O
+and	O
+memory	O
+as	O
+well	O
+as	O
+the	O
+effect	O
+of	O
+topiramate	B-Chemical
+,	O
+a	O
+previously	O
+proposed	O
+therapy	O
+for	O
+cocaine	B-Disease
+addiction	I-Disease
+,	O
+were	O
+evaluated	O
+in	O
+an	O
+experimental	O
+model	O
+of	O
+cocaine	B-Chemical
+administration	O
+in	O
+rats	O
+.	O
+
+NFkappaB	O
+activity	O
+was	O
+decreased	O
+in	O
+the	O
+frontal	O
+cortex	O
+of	O
+cocaine	B-Chemical
+treated	O
+rats	O
+,	O
+as	O
+well	O
+as	O
+GSH	B-Chemical
+concentration	O
+and	O
+glutathione	B-Chemical
+peroxidase	O
+activity	O
+in	O
+the	O
+hippocampus	O
+,	O
+whereas	O
+nNOS	O
+activity	O
+in	O
+the	O
+hippocampus	O
+was	O
+increased	O
+.	O
+
+Memory	O
+retrieval	O
+of	O
+experiences	O
+acquired	O
+prior	O
+to	O
+cocaine	B-Chemical
+administration	O
+was	O
+impaired	O
+and	O
+negatively	O
+correlated	O
+with	O
+NFkappaB	O
+activity	O
+in	O
+the	O
+frontal	O
+cortex	O
+.	O
+
+In	O
+contrast	O
+,	O
+learning	O
+of	O
+new	O
+tasks	O
+was	O
+enhanced	O
+and	O
+correlated	O
+with	O
+the	O
+increase	O
+of	O
+nNOS	O
+activity	O
+and	O
+the	O
+decrease	O
+of	O
+glutathione	B-Chemical
+peroxidase	O
+.	O
+
+These	O
+results	O
+provide	O
+evidence	O
+for	O
+a	O
+possible	O
+mechanistic	O
+role	O
+of	O
+oxidative	O
+and	O
+nitrosative	O
+stress	O
+and	O
+NFkappaB	O
+in	O
+the	O
+alterations	O
+induced	O
+by	O
+cocaine	B-Chemical
+.	O
+
+Topiramate	B-Chemical
+prevented	O
+all	O
+the	O
+alterations	O
+observed	O
+,	O
+showing	O
+novel	O
+neuroprotective	O
+properties	O
+.	O
+
+Efficacy	O
+and	O
+safety	O
+of	O
+asenapine	B-Chemical
+in	O
+a	O
+placebo	O
+-	O
+and	O
+haloperidol	B-Chemical
+-	O
+controlled	O
+trial	O
+in	O
+patients	O
+with	O
+acute	O
+exacerbation	O
+of	O
+schizophrenia	B-Disease
+.	O
+
+Asenapine	B-Chemical
+is	O
+approved	O
+by	O
+the	O
+Food	O
+and	O
+Drugs	O
+Administration	O
+in	O
+adults	O
+for	O
+acute	O
+treatment	O
+of	O
+schizophrenia	B-Disease
+or	O
+of	O
+manic	B-Disease
+or	O
+mixed	O
+episodes	O
+associated	O
+with	O
+bipolar	B-Disease
+I	I-Disease
+disorder	I-Disease
+with	O
+or	O
+without	O
+psychotic	B-Disease
+features	O
+.	O
+
+In	O
+a	O
+double	O
+-	O
+blind	O
+6	O
+-	O
+week	O
+trial	O
+,	O
+458	O
+patients	O
+with	O
+acute	O
+schizophrenia	B-Disease
+were	O
+randomly	O
+assigned	O
+to	O
+fixed	O
+-	O
+dose	O
+treatment	O
+with	O
+asenapine	B-Chemical
+at	O
+5	O
+mg	O
+twice	O
+daily	O
+(	O
+BID	O
+)	O
+,	O
+asenapine	B-Chemical
+at	O
+10	O
+mg	O
+BID	O
+,	O
+placebo	O
+,	O
+or	O
+haloperidol	B-Chemical
+at	O
+4	O
+mg	O
+BID	O
+(	O
+to	O
+verify	O
+assay	O
+sensitivity	O
+)	O
+.	O
+
+With	O
+last	O
+observations	O
+carried	O
+forward	O
+(	O
+LOCF	O
+)	O
+,	O
+mean	O
+Positive	O
+and	O
+Negative	O
+Syndrome	O
+Scale	O
+total	O
+score	O
+reductions	O
+from	O
+baseline	O
+to	O
+endpoint	O
+were	O
+significantly	O
+greater	O
+with	O
+asenapine	B-Chemical
+at	O
+5	O
+mg	O
+BID	O
+(	O
+-	O
+16	O
+.	O
+2	O
+)	O
+and	O
+haloperidol	B-Chemical
+(	O
+-	O
+15	O
+.	O
+4	O
+)	O
+than	O
+placebo	O
+(	O
+-	O
+10	O
+.	O
+7	O
+;	O
+both	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+;	O
+using	O
+mixed	O
+model	O
+for	O
+repeated	O
+measures	O
+(	O
+MMRM	O
+)	O
+,	O
+changes	O
+at	O
+day	O
+42	O
+were	O
+significantly	O
+greater	O
+with	O
+asenapine	B-Chemical
+at	O
+5	O
+and	O
+10	O
+mg	O
+BID	O
+(	O
+-	O
+21	O
+.	O
+3	O
+and	O
+-	O
+19	O
+.	O
+4	O
+,	O
+respectively	O
+)	O
+and	O
+haloperidol	B-Chemical
+(	O
+-	O
+20	O
+.	O
+0	O
+)	O
+than	O
+placebo	O
+(	O
+-	O
+14	O
+.	O
+6	O
+;	O
+all	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+On	O
+the	O
+Positive	O
+and	O
+Negative	O
+Syndrome	O
+Scale	O
+positive	O
+subscale	O
+,	O
+all	O
+treatments	O
+were	O
+superior	O
+to	O
+placebo	O
+with	O
+LOCF	O
+and	O
+MMRM	O
+;	O
+asenapine	B-Chemical
+at	O
+5	O
+mg	O
+BID	O
+was	O
+superior	O
+to	O
+placebo	O
+on	O
+the	O
+negative	O
+subscale	O
+with	O
+MMRM	O
+and	O
+on	O
+the	O
+general	O
+psychopathology	O
+subscale	O
+with	O
+LOCF	O
+and	O
+MMRM	O
+.	O
+
+Treatment	O
+-	O
+related	O
+adverse	O
+events	O
+(	O
+AEs	O
+)	O
+occurred	O
+in	O
+44	O
+%	O
+and	O
+52	O
+%	O
+,	O
+57	O
+%	O
+,	O
+and	O
+41	O
+%	O
+of	O
+the	O
+asenapine	B-Chemical
+at	O
+5	O
+and	O
+10	O
+mg	O
+BID	O
+,	O
+haloperidol	B-Chemical
+,	O
+and	O
+placebo	O
+groups	O
+,	O
+respectively	O
+.	O
+
+Extrapyramidal	B-Disease
+symptoms	I-Disease
+reported	O
+as	O
+AEs	O
+occurred	O
+in	O
+15	O
+%	O
+and	O
+18	O
+%	O
+,	O
+34	O
+%	O
+,	O
+and	O
+10	O
+%	O
+of	O
+the	O
+asenapine	B-Chemical
+at	O
+5	O
+and	O
+10	O
+mg	O
+BID	O
+,	O
+haloperidol	B-Chemical
+,	O
+and	O
+placebo	O
+groups	O
+,	O
+respectively	O
+.	O
+
+Across	O
+all	O
+groups	O
+,	O
+no	O
+more	O
+than	O
+5	O
+%	O
+of	O
+patients	O
+had	O
+clinically	O
+significant	O
+weight	O
+change	O
+.	O
+
+Post	O
+hoc	O
+analyses	O
+indicated	O
+that	O
+efficacy	O
+was	O
+similar	O
+with	O
+asenapine	B-Chemical
+and	O
+haloperidol	B-Chemical
+;	O
+greater	O
+contrasts	O
+were	O
+seen	O
+in	O
+AEs	O
+,	O
+especially	O
+extrapyramidal	B-Disease
+symptoms	I-Disease
+.	O
+
+Salvage	O
+therapy	O
+with	O
+nelarabine	B-Chemical
+,	O
+etoposide	B-Chemical
+,	O
+and	O
+cyclophosphamide	B-Chemical
+in	O
+relapsed	O
+/	O
+refractory	O
+paediatric	O
+T	B-Disease
+-	I-Disease
+cell	I-Disease
+lymphoblastic	I-Disease
+leukaemia	I-Disease
+and	I-Disease
+lymphoma	I-Disease
+.	O
+
+A	O
+combination	O
+of	O
+5	O
+d	O
+of	O
+nelarabine	B-Chemical
+(	O
+AraG	B-Chemical
+)	O
+with	O
+5	O
+d	O
+of	O
+etoposide	B-Chemical
+(	O
+VP	B-Chemical
+)	O
+and	O
+cyclophosphamide	B-Chemical
+(	O
+CPM	B-Chemical
+)	O
+and	O
+prophylactic	O
+intrathecal	O
+chemotherapy	O
+was	O
+used	O
+as	O
+salvage	O
+therapy	O
+in	O
+seven	O
+children	O
+with	O
+refractory	O
+or	O
+relapsed	O
+T	B-Disease
+-	I-Disease
+cell	I-Disease
+leukaemia	I-Disease
+or	I-Disease
+lymphoma	I-Disease
+.	O
+
+The	O
+most	O
+common	O
+side	O
+effects	O
+attributable	O
+to	O
+the	O
+AraG	B-Chemical
+included	O
+Grade	O
+2	O
+and	O
+3	O
+sensory	O
+and	O
+motor	O
+neuropathy	B-Disease
+and	O
+musculoskeletal	B-Disease
+pain	I-Disease
+.	O
+
+Haematological	B-Disease
+toxicity	I-Disease
+was	O
+greater	O
+for	O
+the	O
+combination	O
+than	O
+AraG	B-Chemical
+alone	O
+,	O
+although	O
+median	O
+time	O
+to	O
+neutrophil	O
+and	O
+platelet	O
+recovery	O
+was	O
+consistent	O
+with	O
+other	O
+salvage	O
+therapies	O
+.	O
+
+All	O
+patients	O
+had	O
+some	O
+response	O
+to	O
+the	O
+combined	O
+therapy	O
+and	O
+five	O
+of	O
+the	O
+seven	O
+went	O
+into	O
+complete	O
+remission	O
+after	O
+one	O
+or	O
+two	O
+courses	O
+of	O
+AraG	B-Chemical
+/	O
+VP	B-Chemical
+/	O
+CPM	B-Chemical
+.	O
+
+Our	O
+experience	O
+supports	O
+the	O
+safety	O
+of	O
+giving	O
+AraG	B-Chemical
+as	O
+salvage	O
+therapy	O
+in	O
+synchrony	O
+with	O
+etoposide	B-Chemical
+and	O
+cyclophosphamide	B-Chemical
+,	O
+although	O
+neurological	B-Disease
+toxicity	I-Disease
+must	O
+be	O
+closely	O
+monitored	O
+.	O
+
+Effect	O
+of	O
+adriamycin	B-Chemical
+combined	O
+with	O
+whole	O
+body	O
+hyperthermia	B-Disease
+on	O
+tumor	B-Disease
+and	O
+normal	O
+tissues	O
+.	O
+
+Thermal	O
+enhancement	O
+of	O
+Adriamycin	B-Chemical
+-	O
+mediated	O
+antitumor	O
+activity	O
+and	O
+normal	O
+tissue	O
+toxicities	B-Disease
+by	O
+whole	O
+body	O
+hyperthermia	B-Disease
+were	O
+compared	O
+using	O
+a	O
+F344	O
+rat	O
+model	O
+.	O
+
+Antitumor	O
+activity	O
+was	O
+studied	O
+using	O
+a	O
+tumor	B-Disease
+growth	O
+delay	O
+assay	O
+.	O
+
+Acute	O
+normal	O
+tissue	O
+toxicities	B-Disease
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+leukopenia	B-Disease
+and	O
+thrombocytopenia	B-Disease
+)	O
+and	O
+late	O
+normal	O
+tissue	O
+toxicities	B-Disease
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+myocardial	B-Disease
+and	I-Disease
+kidney	I-Disease
+injury	I-Disease
+)	O
+were	O
+evaluated	O
+by	O
+functional	O
+/	O
+physiological	O
+assays	O
+and	O
+by	O
+morphological	O
+techniques	O
+.	O
+
+Whole	O
+body	O
+hyperthermia	B-Disease
+(	O
+120	O
+min	O
+at	O
+41	O
+.	O
+5	O
+degrees	O
+C	O
+)	O
+enhanced	O
+both	O
+Adriamycin	B-Chemical
+-	O
+mediated	O
+antitumor	O
+activity	O
+and	O
+toxic	O
+side	O
+effects	O
+.	O
+
+The	O
+thermal	O
+enhancement	O
+ratio	O
+calculated	O
+for	O
+antitumor	O
+activity	O
+was	O
+1	O
+.	O
+6	O
+.	O
+
+Thermal	O
+enhancement	O
+ratios	O
+estimated	O
+for	O
+"	O
+acute	O
+"	O
+hematological	O
+changes	O
+were	O
+1	O
+.	O
+3	O
+,	O
+whereas	O
+those	O
+estimated	O
+for	O
+"	O
+late	O
+"	O
+damage	O
+(	O
+based	O
+on	O
+morphological	O
+cardiac	B-Disease
+and	I-Disease
+renal	I-Disease
+lesions	I-Disease
+)	O
+varied	O
+between	O
+2	O
+.	O
+4	O
+and	O
+4	O
+.	O
+3	O
+.	O
+
+Thus	O
+,	O
+while	O
+whole	O
+body	O
+hyperthermia	B-Disease
+enhances	O
+Adriamycin	B-Chemical
+-	O
+mediated	O
+antitumor	O
+effect	O
+,	O
+normal	O
+tissue	O
+toxicity	B-Disease
+is	O
+also	O
+increased	O
+,	O
+and	O
+the	O
+potential	O
+therapeutic	O
+gain	O
+of	O
+the	O
+combined	O
+modality	O
+treatment	O
+is	O
+eroded	O
+.	O
+
+Permeability	O
+,	O
+ultrastructural	O
+changes	O
+,	O
+and	O
+distribution	O
+of	O
+novel	O
+proteins	O
+in	O
+the	O
+glomerular	O
+barrier	O
+in	O
+early	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+nephrosis	B-Disease
+.	O
+
+BACKGROUND	O
+/	O
+AIMS	O
+:	O
+It	O
+is	O
+still	O
+unclear	O
+what	O
+happens	O
+in	O
+the	O
+glomerulus	O
+when	O
+proteinuria	B-Disease
+starts	O
+.	O
+
+Using	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+nephrosis	B-Disease
+(	O
+PAN	O
+)	O
+rats	O
+,	O
+we	O
+studied	O
+early	O
+ultrastructural	O
+and	O
+permeability	O
+changes	O
+in	O
+relation	O
+to	O
+the	O
+expression	O
+of	O
+the	O
+podocyte	O
+-	O
+associated	O
+molecules	O
+nephrin	O
+,	O
+a	O
+-	O
+actinin	O
+,	O
+dendrin	O
+,	O
+and	O
+plekhh2	O
+,	O
+the	O
+last	O
+two	O
+of	O
+which	O
+were	O
+only	O
+recently	O
+discovered	O
+in	O
+podocytes	O
+.	O
+
+METHODS	O
+:	O
+Using	O
+immune	O
+stainings	O
+,	O
+semiquantitative	O
+measurement	O
+was	O
+performed	O
+under	O
+the	O
+electron	O
+microscope	O
+.	O
+
+Permeability	O
+was	O
+assessed	O
+using	O
+isolated	O
+kidney	O
+perfusion	O
+with	O
+tracers	O
+.	O
+
+Possible	O
+effects	O
+of	O
+ACE	O
+inhibition	O
+were	O
+tested	O
+.	O
+
+RESULTS	O
+:	O
+By	O
+day	O
+2	O
+,	O
+some	O
+patchy	O
+foot	O
+process	O
+effacement	O
+,	O
+but	O
+no	O
+proteinuria	B-Disease
+,	O
+appeared	O
+.	O
+
+The	O
+amount	O
+of	O
+nephrin	O
+was	O
+reduced	O
+in	O
+both	O
+diseased	O
+and	O
+normal	O
+areas	O
+.	O
+
+The	O
+other	O
+proteins	O
+showed	O
+few	O
+changes	O
+,	O
+which	O
+were	O
+limited	O
+to	O
+diseased	O
+areas	O
+.	O
+
+By	O
+day	O
+4	O
+,	O
+foot	O
+process	O
+effacement	O
+was	O
+complete	O
+and	O
+proteinuria	B-Disease
+appeared	O
+in	O
+parallel	O
+with	O
+signs	O
+of	O
+size	O
+barrier	O
+damage	O
+.	O
+
+Nephrin	O
+decreased	O
+further	O
+,	O
+while	O
+dendrin	O
+and	O
+plekhh2	O
+also	O
+decreased	O
+but	O
+a	O
+-	O
+actinin	O
+remained	O
+unchanged	O
+.	O
+
+ACE	O
+inhibition	O
+had	O
+no	O
+significant	O
+protective	O
+effect	O
+.	O
+
+CONCLUSIONS	O
+:	O
+PAN	O
+glomeruli	O
+already	O
+showed	O
+significant	O
+pathology	O
+by	O
+day	O
+4	O
+,	O
+despite	O
+relatively	O
+mild	O
+proteinuria	B-Disease
+.	O
+
+This	O
+was	O
+preceded	O
+by	O
+altered	O
+nephrin	O
+expression	O
+,	O
+supporting	O
+its	O
+pivotal	O
+role	O
+in	O
+podocyte	O
+morphology	O
+.	O
+
+The	O
+novel	O
+proteins	O
+dendrin	O
+and	O
+plekhh2	O
+were	O
+both	O
+reduced	O
+,	O
+suggesting	O
+roles	O
+in	O
+PAN	O
+,	O
+whereas	O
+a	O
+-	O
+actinin	O
+was	O
+unchanged	O
+.	O
+
+A	O
+novel	O
+,	O
+multiple	O
+symptom	O
+model	O
+of	O
+obsessive	B-Disease
+-	I-Disease
+compulsive	I-Disease
+-	I-Disease
+like	I-Disease
+behaviors	I-Disease
+in	O
+animals	O
+.	O
+
+BACKGROUND	O
+:	O
+Current	O
+animal	O
+models	O
+of	O
+obsessive	B-Disease
+-	I-Disease
+compulsive	I-Disease
+disorder	I-Disease
+(	O
+OCD	B-Disease
+)	O
+typically	O
+involve	O
+acute	O
+,	O
+drug	O
+-	O
+induced	O
+symptom	O
+provocation	O
+or	O
+a	O
+genetic	O
+association	O
+with	O
+stereotypies	O
+or	O
+anxiety	B-Disease
+.	O
+
+None	O
+of	O
+these	O
+current	O
+models	O
+demonstrate	O
+multiple	O
+OCD	B-Disease
+-	O
+like	O
+behaviors	O
+.	O
+
+METHODS	O
+:	O
+Neonatal	O
+rats	O
+were	O
+treated	O
+with	O
+the	O
+tricyclic	O
+antidepressant	B-Chemical
+clomipramine	B-Chemical
+or	O
+vehicle	O
+between	O
+days	O
+9	O
+and	O
+16	O
+twice	O
+daily	O
+and	O
+behaviorally	O
+tested	O
+in	O
+adulthood	O
+.	O
+
+RESULTS	O
+:	O
+Clomipramine	B-Chemical
+exposure	O
+in	O
+immature	O
+rats	O
+produced	O
+significant	O
+behavioral	O
+and	O
+biochemical	O
+changes	O
+that	O
+include	O
+enhanced	O
+anxiety	B-Disease
+(	O
+elevated	O
+plus	O
+maze	O
+and	O
+marble	O
+burying	O
+)	O
+,	O
+behavioral	B-Disease
+inflexibility	I-Disease
+(	O
+perseveration	O
+in	O
+the	O
+spontaneous	O
+alternation	O
+task	O
+and	O
+impaired	O
+reversal	O
+learning	O
+)	O
+,	O
+working	O
+memory	B-Disease
+impairment	I-Disease
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+win	O
+-	O
+shift	O
+paradigm	O
+)	O
+,	O
+hoarding	B-Disease
+,	O
+and	O
+corticostriatal	B-Disease
+dysfunction	I-Disease
+.	O
+
+Dopamine	B-Chemical
+D2	O
+receptors	O
+were	O
+elevated	O
+in	O
+the	O
+striatum	O
+,	O
+whereas	O
+serotonin	B-Chemical
+2C	O
+,	O
+but	O
+not	O
+serotonin	B-Chemical
+1A	O
+,	O
+receptors	O
+were	O
+elevated	O
+in	O
+the	O
+orbital	O
+frontal	O
+cortex	O
+.	O
+
+CONCLUSIONS	O
+:	O
+This	O
+is	O
+the	O
+first	O
+demonstration	O
+of	O
+multiple	O
+symptoms	O
+consistent	O
+with	O
+an	O
+OCD	B-Disease
+-	O
+like	O
+profile	O
+in	O
+animals	O
+.	O
+
+Moreover	O
+,	O
+these	O
+behaviors	O
+are	O
+accompanied	O
+by	O
+biochemical	O
+changes	O
+in	O
+brain	O
+regions	O
+previously	O
+identified	O
+as	O
+relevant	O
+to	O
+OCD	B-Disease
+.	O
+
+This	O
+novel	O
+model	O
+of	O
+OCD	B-Disease
+demonstrates	O
+that	O
+drug	O
+exposure	O
+during	O
+a	O
+sensitive	O
+period	O
+can	O
+program	O
+disease	O
+-	O
+like	O
+systems	O
+permanently	O
+,	O
+which	O
+could	O
+have	O
+implications	O
+for	O
+current	O
+and	O
+future	O
+therapeutic	O
+strategies	O
+for	O
+this	O
+and	O
+other	O
+psychiatric	B-Disease
+disorders	I-Disease
+.	O
+
+Elevation	O
+of	O
+ADAM10	O
+,	O
+ADAM17	O
+,	O
+MMP	O
+-	O
+2	O
+and	O
+MMP	O
+-	O
+9	O
+expression	O
+with	O
+media	O
+degeneration	O
+features	O
+CaCl2	B-Chemical
+-	O
+induced	O
+thoracic	B-Disease
+aortic	I-Disease
+aneurysm	I-Disease
+in	O
+a	O
+rat	O
+model	O
+.	O
+
+PURPOSE	O
+:	O
+This	O
+study	O
+was	O
+designed	O
+to	O
+establish	O
+a	O
+rat	O
+model	O
+of	O
+thoracic	B-Disease
+aortic	I-Disease
+aneurysm	I-Disease
+(	O
+TAA	B-Disease
+)	O
+by	O
+calcium	B-Chemical
+chloride	I-Chemical
+(	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+)	O
+-	O
+induced	O
+arterial	B-Disease
+injury	I-Disease
+and	O
+to	O
+explore	O
+the	O
+potential	O
+role	O
+of	O
+a	O
+disintegrin	O
+and	O
+metalloproteinase	O
+(	O
+ADAM	O
+)	O
+,	O
+matrix	O
+metalloproteinases	O
+(	O
+MMPs	O
+)	O
+and	O
+their	O
+endogenous	O
+inhibitors	O
+(	O
+TIMPs	O
+)	O
+in	O
+TAA	B-Disease
+formation	O
+.	O
+
+METHODS	O
+:	O
+Thoracic	O
+aorta	O
+of	O
+male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+was	O
+exposed	O
+to	O
+0	O
+.	O
+5M	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+or	O
+normal	O
+saline	O
+(	O
+NaCl	B-Chemical
+)	O
+.	O
+
+After	O
+12weeks	O
+,	O
+animals	O
+were	O
+euthanized	O
+,	O
+and	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+,	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+untreated	O
+(	O
+n	O
+=	O
+12	O
+)	O
+and	O
+NaCl	B-Chemical
+-	O
+treated	O
+aortic	O
+segments	O
+(	O
+n	O
+=	O
+12	O
+)	O
+were	O
+collected	O
+for	O
+histological	O
+and	O
+molecular	O
+assessments	O
+.	O
+
+MMP	O
+-	O
+TIMP	O
+and	O
+ADAM	O
+mRNAs	O
+were	O
+semi	O
+-	O
+quantitatively	O
+analyzed	O
+and	O
+protein	O
+expressions	O
+were	O
+determined	O
+by	O
+immunohistochemistry	O
+.	O
+
+RESULTS	O
+:	O
+Despite	O
+similar	O
+external	O
+diameters	O
+among	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+,	O
+non	O
+-	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+and	O
+NaCl	B-Chemical
+-	O
+treated	O
+segments	O
+,	O
+aneurymal	O
+alteration	O
+(	O
+n	O
+=	O
+6	O
+,	O
+50	O
+%	O
+)	O
+,	O
+media	O
+degeneration	O
+with	O
+regional	O
+disruption	O
+,	O
+fragmentation	O
+of	O
+elastic	O
+fiber	O
+,	O
+and	O
+increased	O
+collagen	O
+deposition	O
+(	O
+n	O
+=	O
+12	O
+,	O
+100	O
+%	O
+)	O
+were	O
+demonstrated	O
+in	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+segments	O
+.	O
+
+MMP	O
+-	O
+2	O
+,	O
+MMP	O
+-	O
+9	O
+,	O
+ADAM	O
+-	O
+10	O
+and	O
+ADAM	O
+-	O
+17	O
+mRNA	O
+levels	O
+were	O
+increased	O
+in	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+segments	O
+(	O
+all	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+with	O
+trends	O
+of	O
+elevation	O
+in	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+untreated	O
+segments	O
+,	O
+as	O
+compared	O
+with	O
+NaCl	B-Chemical
+-	O
+treated	O
+segments	O
+.	O
+
+Immunohistochemistry	O
+displayed	O
+significantly	O
+increased	O
+expressions	O
+of	O
+MMP	O
+-	O
+2	O
+,	O
+MMP	O
+-	O
+9	O
+,	O
+ADAM	O
+-	O
+10	O
+and	O
+ADAM	O
+-	O
+17	O
+(	O
+all	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+in	O
+intima	O
+and	O
+media	O
+for	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+-	O
+treated	O
+segments	O
+.	O
+
+TIMP	O
+mRNA	O
+and	O
+tissue	O
+levels	O
+did	O
+not	O
+differ	O
+obviously	O
+among	O
+the	O
+three	O
+aortic	O
+segments	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+study	O
+establishes	O
+a	O
+TAA	B-Disease
+model	O
+by	O
+periarterial	O
+CaCl	B-Chemical
+(	I-Chemical
+2	I-Chemical
+)	I-Chemical
+exposure	O
+in	O
+rats	O
+,	O
+and	O
+demonstrates	O
+a	O
+significant	O
+elevation	O
+of	O
+expression	O
+of	O
+MMP	O
+-	O
+2	O
+,	O
+MMP	O
+-	O
+9	O
+,	O
+ADAM10	O
+and	O
+ADAM17	O
+in	O
+the	O
+pathogenesis	O
+of	O
+vascular	O
+remodeling	O
+.	O
+
+Suxamethonium	B-Chemical
+induced	O
+prolonged	O
+apnea	B-Disease
+in	O
+a	O
+patient	O
+receiving	O
+electroconvulsive	O
+therapy	O
+.	O
+
+Suxamethonium	B-Chemical
+causes	O
+prolonged	O
+apnea	B-Disease
+in	O
+patients	O
+in	O
+whom	O
+pseudocholinesterase	O
+enzyme	O
+gets	O
+deactivated	O
+by	O
+organophosphorus	B-Chemical
+(	I-Chemical
+OP	I-Chemical
+)	I-Chemical
+poisons	I-Chemical
+.	O
+
+Here	O
+,	O
+we	O
+present	O
+a	O
+similar	O
+incident	O
+in	O
+a	O
+severely	O
+depressed	B-Disease
+patient	O
+who	O
+received	O
+electroconvulsive	O
+therapy	O
+(	O
+ECT	O
+)	O
+.	O
+
+Prolonged	O
+apnea	B-Disease
+in	O
+our	O
+case	O
+ensued	O
+because	O
+the	O
+information	O
+about	O
+suicidal	O
+attempt	O
+by	O
+OP	B-Chemical
+compound	I-Chemical
+was	O
+concealed	O
+from	O
+the	O
+treating	O
+team	O
+.	O
+
+Curcumin	B-Chemical
+ameliorates	O
+cognitive	B-Disease
+dysfunction	I-Disease
+and	O
+oxidative	O
+damage	O
+in	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+administered	O
+rats	O
+.	O
+
+The	O
+antiepileptic	O
+drugs	O
+,	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+are	O
+well	O
+known	O
+to	O
+cause	O
+cognitive	B-Disease
+impairment	I-Disease
+on	O
+chronic	O
+use	O
+.	O
+
+The	O
+increase	O
+in	O
+free	O
+radical	O
+generation	O
+has	O
+been	O
+implicated	O
+as	O
+one	O
+of	O
+the	O
+important	O
+mechanisms	O
+of	O
+cognitive	B-Disease
+impairment	I-Disease
+by	O
+antiepileptic	O
+drugs	O
+.	O
+
+Curcumin	B-Chemical
+has	O
+shown	O
+antioxidant	O
+,	O
+anti	O
+-	O
+inflammatory	O
+and	O
+neuro	O
+-	O
+protective	O
+properties	O
+.	O
+
+Therefore	O
+,	O
+the	O
+present	O
+study	O
+was	O
+carried	O
+out	O
+to	O
+investigate	O
+the	O
+effect	O
+of	O
+chronic	O
+curcumin	B-Chemical
+administration	O
+on	O
+phenobarbitone	B-Chemical
+-	O
+and	O
+carbamazepine	B-Chemical
+-	O
+induced	O
+cognitive	B-Disease
+impairment	I-Disease
+and	O
+oxidative	O
+stress	O
+in	O
+rats	O
+.	O
+
+Pharmacokinetic	O
+interactions	O
+of	O
+curcumin	B-Chemical
+with	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+were	O
+also	O
+studied	O
+.	O
+
+Vehicle	O
+/	O
+drugs	O
+were	O
+administered	O
+daily	O
+for	O
+21days	O
+to	O
+male	O
+Wistar	O
+rats	O
+.	O
+
+Passive	O
+avoidance	O
+paradigm	O
+and	O
+elevated	O
+plus	O
+maze	O
+test	O
+were	O
+used	O
+to	O
+assess	O
+cognitive	O
+function	O
+.	O
+
+At	O
+the	O
+end	O
+of	O
+study	O
+period	O
+,	O
+serum	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+,	O
+whole	O
+brain	O
+malondialdehyde	B-Chemical
+and	O
+reduced	O
+glutathione	B-Chemical
+levels	O
+were	O
+estimated	O
+.	O
+
+The	O
+administration	O
+of	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+for	O
+21days	O
+caused	O
+a	O
+significant	O
+impairment	B-Disease
+of	I-Disease
+learning	I-Disease
+and	I-Disease
+memory	I-Disease
+as	O
+well	O
+as	O
+an	O
+increased	O
+oxidative	O
+stress	O
+.	O
+
+Concomitant	O
+curcumin	B-Chemical
+administration	O
+prevented	O
+the	O
+cognitive	B-Disease
+impairment	I-Disease
+and	O
+decreased	O
+the	O
+increased	O
+oxidative	O
+stress	O
+induced	O
+by	O
+these	O
+antiepileptic	O
+drugs	O
+.	O
+
+Curcumin	B-Chemical
+co	O
+-	O
+administration	O
+did	O
+not	O
+cause	O
+any	O
+significant	O
+alteration	O
+in	O
+the	O
+serum	O
+concentrations	O
+of	O
+both	O
+phenobarbitone	B-Chemical
+as	O
+well	O
+as	O
+carbamazepine	B-Chemical
+.	O
+
+These	O
+results	O
+show	O
+that	O
+curcumin	B-Chemical
+has	O
+beneficial	O
+effect	O
+in	O
+mitigating	O
+the	O
+deterioration	B-Disease
+of	I-Disease
+cognitive	I-Disease
+functions	I-Disease
+and	O
+oxidative	O
+damage	O
+in	O
+rats	O
+treated	O
+with	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+without	O
+significantly	O
+altering	O
+their	O
+serum	O
+concentrations	O
+.	O
+
+The	O
+findings	O
+suggest	O
+that	O
+curcumin	B-Chemical
+can	O
+be	O
+considered	O
+as	O
+a	O
+potential	O
+safe	O
+and	O
+effective	O
+adjuvant	O
+to	O
+phenobarbitone	B-Chemical
+and	O
+carbamazepine	B-Chemical
+therapy	O
+in	O
+preventing	O
+cognitive	B-Disease
+impairment	I-Disease
+associated	O
+with	O
+these	O
+drugs	O
+.	O
+
+Can	O
+angiogenesis	O
+be	O
+a	O
+target	O
+of	O
+treatment	O
+for	O
+ribavirin	B-Chemical
+associated	O
+hemolytic	B-Disease
+anemia	I-Disease
+?	O
+
+BACKGROUND	O
+/	O
+AIMS	O
+:	O
+Recently	O
+ribavirin	B-Chemical
+has	O
+been	O
+found	O
+to	O
+inhibit	O
+angiogenesis	O
+and	O
+a	O
+number	O
+of	O
+angiogenesis	O
+inhibitors	O
+such	O
+as	O
+sunitinib	B-Chemical
+and	O
+sorafenib	B-Chemical
+have	O
+been	O
+found	O
+to	O
+cause	O
+acute	O
+hemolysis	B-Disease
+.	O
+
+We	O
+aimed	O
+to	O
+investigate	O
+whether	O
+there	O
+is	O
+a	O
+relation	O
+between	O
+hemoglobin	O
+,	O
+haptoglobin	O
+and	O
+angiogenesis	O
+soluble	O
+markers	O
+which	O
+are	O
+modifiable	O
+and	O
+can	O
+help	O
+in	O
+developing	O
+strategies	O
+against	O
+anemia	B-Disease
+.	O
+
+METHODS	O
+:	O
+Fourteen	O
+patients	O
+chronically	B-Disease
+infected	I-Disease
+with	I-Disease
+hepatitis	I-Disease
+C	I-Disease
+virus	I-Disease
+were	O
+treated	O
+by	O
+pegylated	B-Chemical
+interferon	I-Chemical
+alpha	I-Chemical
+2a	I-Chemical
+and	O
+ribavirin	B-Chemical
+.	O
+
+Serum	O
+hemoglobin	O
+,	O
+haptoglobin	O
+and	O
+angiogenesis	O
+markers	O
+of	O
+vascular	O
+endothelial	O
+growth	O
+factor	O
+and	O
+angiopoetin	O
+-	O
+2	O
+were	O
+investigated	O
+before	O
+and	O
+after	O
+therapy	O
+.	O
+
+RESULTS	O
+:	O
+We	O
+observed	O
+a	O
+significant	O
+decrease	O
+in	O
+haptoglobin	O
+levels	O
+at	O
+the	O
+end	O
+of	O
+the	O
+treatment	O
+period	O
+.	O
+
+Hemoglobin	O
+levels	O
+also	O
+decreased	O
+but	O
+insignificantly	O
+by	O
+treatment	O
+.	O
+
+In	O
+contrast	O
+with	O
+the	O
+literature	O
+,	O
+serum	O
+levels	O
+of	O
+angiogenesis	O
+factors	O
+did	O
+not	O
+change	O
+significantly	O
+by	O
+pegylated	B-Chemical
+interferon	I-Chemical
+and	O
+ribavirin	B-Chemical
+therapy	O
+.	O
+
+We	O
+found	O
+no	O
+correlation	O
+of	O
+angiogenesis	O
+soluble	O
+markers	O
+with	O
+either	O
+hemoglobin	O
+or	O
+haptoglobin	O
+.	O
+
+CONCLUSION	O
+:	O
+This	O
+is	O
+the	O
+first	O
+study	O
+in	O
+the	O
+literature	O
+investigating	O
+a	O
+link	O
+between	O
+angiogenesis	O
+soluble	O
+markers	O
+and	O
+ribavirin	B-Chemical
+induced	O
+anemia	B-Disease
+in	O
+patients	O
+with	O
+hepatitis	B-Disease
+C	I-Disease
+and	O
+we	O
+could	O
+not	O
+find	O
+any	O
+relation	O
+.	O
+
+Future	O
+research	O
+with	O
+larger	O
+number	O
+of	O
+patients	O
+is	O
+needed	O
+to	O
+find	O
+out	O
+modifiable	O
+factors	O
+that	O
+will	O
+improve	O
+the	O
+safety	O
+of	O
+ribavirin	B-Chemical
+therapy	O
+.	O
+
+Reduction	O
+in	O
+injection	O
+pain	B-Disease
+using	O
+buffered	O
+lidocaine	B-Chemical
+as	O
+a	O
+local	O
+anesthetic	O
+before	O
+cardiac	O
+catheterization	O
+.	O
+
+Previous	O
+reports	O
+have	O
+suggested	O
+that	O
+pain	B-Disease
+associated	O
+with	O
+the	O
+injection	O
+of	O
+lidocaine	B-Chemical
+is	O
+related	O
+to	O
+the	O
+acidic	O
+pH	O
+of	O
+the	O
+solution	O
+.	O
+
+To	O
+determine	O
+if	O
+the	O
+addition	O
+of	O
+a	O
+buffering	O
+solution	O
+to	O
+adjust	O
+the	O
+pH	O
+of	O
+lidocaine	B-Chemical
+into	O
+the	O
+physiologic	O
+range	O
+would	O
+reduce	O
+pain	B-Disease
+during	O
+injection	O
+,	O
+we	O
+performed	O
+a	O
+blinded	O
+randomized	O
+study	O
+in	O
+patients	O
+undergoing	O
+cardiac	O
+catheterization	O
+.	O
+
+Twenty	O
+patients	O
+were	O
+asked	O
+to	O
+quantify	O
+the	O
+severity	O
+of	O
+pain	B-Disease
+after	O
+receiving	O
+standard	O
+lidocaine	B-Chemical
+in	O
+one	O
+femoral	O
+area	O
+and	O
+buffered	O
+lidocaine	B-Chemical
+in	O
+the	O
+opposite	O
+femoral	O
+area	O
+.	O
+
+The	O
+mean	O
+pain	B-Disease
+score	O
+for	O
+buffered	O
+lidocaine	B-Chemical
+was	O
+significantly	O
+lower	O
+than	O
+the	O
+mean	O
+score	O
+for	O
+standard	O
+lidocaine	B-Chemical
+(	O
+2	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+9	O
+vs	O
+.	O
+3	O
+.	O
+8	O
++	O
+/	O
+-	O
+2	O
+.	O
+2	O
+,	O
+P	O
+=	O
+0	O
+.	O
+03	O
+)	O
+.	O
+
+The	O
+pH	O
+adjustment	O
+of	O
+standard	O
+lidocaine	B-Chemical
+can	O
+be	O
+accomplished	O
+easily	O
+in	O
+the	O
+catheterization	O
+laboratory	O
+before	O
+injection	O
+and	O
+results	O
+in	O
+a	O
+reduction	O
+of	O
+the	O
+pain	B-Disease
+occurring	O
+during	O
+the	O
+infiltration	O
+of	O
+tissues	O
+.	O
+
+Effect	O
+of	O
+L	B-Chemical
+-	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+glyceryl	I-Chemical
+-	I-Chemical
+phosphorylcholine	I-Chemical
+on	O
+amnesia	B-Disease
+caused	O
+by	O
+scopolamine	B-Chemical
+.	O
+
+The	O
+present	O
+study	O
+was	O
+carried	O
+out	O
+to	O
+test	O
+the	O
+effects	O
+of	O
+L	B-Chemical
+-	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+glycerylphosphorylcholine	I-Chemical
+(	O
+L	B-Chemical
+-	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+GFC	I-Chemical
+)	O
+on	O
+memory	B-Disease
+impairment	I-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+in	O
+man	O
+.	O
+
+Thirty	O
+-	O
+two	O
+healthy	O
+young	O
+volunteers	O
+were	O
+randomly	O
+allocated	O
+to	O
+four	O
+different	O
+groups	O
+.	O
+
+They	O
+were	O
+given	O
+a	O
+ten	O
+day	O
+pretreatment	O
+with	O
+either	O
+L	B-Chemical
+-	I-Chemical
+alpha	I-Chemical
+-	I-Chemical
+GFC	I-Chemical
+or	O
+placebo	O
+,	O
+p	O
+.	O
+o	O
+.	O
+,	O
+and	O
+on	O
+the	O
+eleventh	O
+day	O
+either	O
+scopolamine	B-Chemical
+or	O
+placebo	O
+,	O
+i	O
+.	O
+m	O
+.	O
+
+Before	O
+and	O
+0	O
+.	O
+5	O
+,	O
+1	O
+,	O
+2	O
+,	O
+3	O
+,	O
+and	O
+6	O
+h	O
+after	O
+injection	O
+the	O
+subjects	O
+were	O
+given	O
+attention	O
+and	O
+mnemonic	O
+tests	O
+.	O
+
+The	O
+findings	O
+of	O
+this	O
+study	O
+indicate	O
+that	O
+the	O
+drug	O
+is	O
+able	O
+to	O
+antagonize	O
+impairment	B-Disease
+of	I-Disease
+attention	I-Disease
+and	I-Disease
+memory	I-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+.	O
+
+Safety	O
+of	O
+capecitabine	B-Chemical
+:	O
+a	O
+review	O
+.	O
+
+IMPORTANCE	O
+OF	O
+THE	O
+FIELD	O
+:	O
+Fluoropyrimidines	B-Chemical
+,	O
+in	O
+particular	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+)	O
+,	O
+have	O
+been	O
+the	O
+mainstay	O
+of	O
+treatment	O
+for	O
+several	O
+solid	O
+tumors	B-Disease
+,	O
+including	O
+colorectal	B-Disease
+,	I-Disease
+breast	I-Disease
+and	I-Disease
+head	I-Disease
+and	I-Disease
+neck	I-Disease
+cancers	I-Disease
+,	O
+for	O
+>	O
+40	O
+years	O
+.	O
+
+AREAS	O
+COVERED	O
+IN	O
+THIS	O
+REVIEW	O
+:	O
+This	O
+article	O
+reviews	O
+the	O
+pharmacology	O
+and	O
+efficacy	O
+of	O
+capecitabine	B-Chemical
+with	O
+a	O
+special	O
+emphasis	O
+on	O
+its	O
+safety	O
+.	O
+
+WHAT	O
+THE	O
+READER	O
+WILL	O
+GAIN	O
+:	O
+The	O
+reader	O
+will	O
+gain	O
+better	O
+insight	O
+into	O
+the	O
+safety	O
+of	O
+capecitabine	B-Chemical
+in	O
+special	O
+populations	O
+such	O
+as	O
+patients	O
+with	O
+advanced	O
+age	O
+,	O
+renal	B-Disease
+and	I-Disease
+kidney	I-Disease
+disease	I-Disease
+.	O
+
+We	O
+also	O
+explore	O
+different	O
+dosing	O
+and	O
+schedules	O
+of	O
+capecitabine	B-Chemical
+administration	O
+.	O
+
+TAKE	O
+HOME	O
+MESSAGE	O
+:	O
+Capecitabine	B-Chemical
+is	O
+an	O
+oral	O
+prodrug	O
+of	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+and	O
+was	O
+developed	O
+to	O
+fulfill	O
+the	O
+need	O
+for	O
+a	O
+more	O
+convenient	O
+therapy	O
+and	O
+provide	O
+an	O
+improved	O
+safety	O
+/	O
+efficacy	O
+profile	O
+.	O
+
+It	O
+has	O
+shown	O
+promising	O
+results	O
+alone	O
+or	O
+in	O
+combination	O
+with	O
+other	O
+chemotherapeutic	O
+agents	O
+in	O
+colorectal	B-Disease
+,	I-Disease
+breast	I-Disease
+,	I-Disease
+pancreaticobiliary	I-Disease
+,	I-Disease
+gastric	I-Disease
+,	I-Disease
+renal	I-Disease
+cell	I-Disease
+and	I-Disease
+head	I-Disease
+and	I-Disease
+neck	I-Disease
+cancers	I-Disease
+.	O
+
+The	O
+most	O
+commonly	O
+reported	O
+toxic	O
+effects	O
+of	O
+capecitabine	B-Chemical
+are	O
+diarrhea	B-Disease
+,	O
+nausea	B-Disease
+,	O
+vomiting	B-Disease
+,	O
+stomatitis	B-Disease
+and	O
+hand	B-Disease
+-	I-Disease
+foot	I-Disease
+syndrome	I-Disease
+.	O
+
+Capecitabine	B-Chemical
+has	O
+a	O
+well	O
+-	O
+established	O
+safety	O
+profile	O
+and	O
+can	O
+be	O
+given	O
+safely	O
+to	O
+patients	O
+with	O
+advanced	O
+age	O
+,	O
+hepatic	B-Disease
+and	I-Disease
+renal	I-Disease
+dysfunctions	I-Disease
+.	O
+
+Levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+:	O
+filling	O
+the	O
+bench	O
+-	O
+to	O
+-	O
+bedside	O
+gap	O
+.	O
+
+Levodopa	B-Chemical
+is	O
+the	O
+most	O
+effective	O
+drug	O
+for	O
+the	O
+treatment	O
+of	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+However	O
+,	O
+the	O
+long	O
+-	O
+term	O
+use	O
+of	O
+this	O
+dopamine	B-Chemical
+precursor	O
+is	O
+complicated	O
+by	O
+highly	O
+disabling	O
+fluctuations	O
+and	O
+dyskinesias	B-Disease
+.	O
+
+Although	O
+preclinical	O
+and	O
+clinical	O
+findings	O
+suggest	O
+pulsatile	O
+stimulation	O
+of	O
+striatal	O
+postsynaptic	O
+receptors	O
+as	O
+a	O
+key	O
+mechanism	O
+underlying	O
+levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+,	O
+their	O
+pathogenesis	O
+is	O
+still	O
+unclear	O
+.	O
+
+In	O
+recent	O
+years	O
+,	O
+evidence	O
+from	O
+animal	O
+models	O
+of	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+has	O
+provided	O
+important	O
+information	O
+to	O
+understand	O
+the	O
+effect	O
+of	O
+specific	O
+receptor	O
+and	O
+post	O
+-	O
+receptor	O
+molecular	O
+mechanisms	O
+underlying	O
+the	O
+development	O
+of	O
+dyskinetic	B-Disease
+movements	I-Disease
+.	O
+
+Recent	O
+preclinical	O
+and	O
+clinical	O
+data	O
+from	O
+promising	O
+lines	O
+of	O
+research	O
+focus	O
+on	O
+the	O
+differential	O
+role	O
+of	O
+presynaptic	O
+versus	O
+postsynaptic	O
+mechanisms	O
+,	O
+dopamine	B-Chemical
+receptor	O
+subtypes	O
+,	O
+ionotropic	O
+and	O
+metabotropic	O
+glutamate	B-Chemical
+receptors	O
+,	O
+and	O
+non	O
+-	O
+dopaminergic	O
+neurotransmitter	O
+systems	O
+in	O
+the	O
+pathophysiology	O
+of	O
+levodopa	B-Chemical
+-	O
+induced	O
+dyskinesias	B-Disease
+.	O
+
+Effects	O
+of	O
+pallidal	O
+neurotensin	B-Chemical
+on	O
+haloperidol	B-Chemical
+-	O
+induced	O
+parkinsonian	B-Disease
+catalepsy	I-Disease
+:	O
+behavioral	O
+and	O
+electrophysiological	O
+studies	O
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+globus	O
+pallidus	O
+plays	O
+a	O
+critical	O
+role	O
+in	O
+movement	O
+regulation	O
+.	O
+
+Previous	O
+studies	O
+have	O
+indicated	O
+that	O
+the	O
+globus	O
+pallidus	O
+receives	O
+neurotensinergic	O
+innervation	O
+from	O
+the	O
+striatum	O
+,	O
+and	O
+systemic	O
+administration	O
+of	O
+a	O
+neurotensin	B-Chemical
+analog	O
+could	O
+produce	O
+antiparkinsonian	O
+effects	O
+.	O
+
+The	O
+present	O
+study	O
+aimed	O
+to	O
+investigate	O
+the	O
+effects	O
+of	O
+pallidal	O
+neurotensin	B-Chemical
+on	O
+haloperidol	B-Chemical
+-	O
+induced	O
+parkinsonian	B-Disease
+symptoms	I-Disease
+.	O
+
+METHODS	O
+:	O
+Behavioral	O
+experiments	O
+and	O
+electrophysiological	O
+recordings	O
+were	O
+performed	O
+in	O
+the	O
+present	O
+study	O
+.	O
+
+RESULTS	O
+:	O
+Bilateral	O
+infusions	O
+of	O
+neurotensin	B-Chemical
+into	O
+the	O
+globus	O
+pallidus	O
+reversed	O
+haloperidol	B-Chemical
+-	O
+induced	O
+parkinsonian	B-Disease
+catalepsy	I-Disease
+in	O
+rats	O
+.	O
+
+Electrophysiological	O
+recordings	O
+showed	O
+that	O
+microinjection	O
+of	O
+neurotensin	B-Chemical
+induced	O
+excitation	O
+of	O
+pallidal	O
+neurons	O
+in	O
+the	O
+presence	O
+of	O
+systemic	O
+haloperidol	B-Chemical
+administration	O
+.	O
+
+The	O
+neurotensin	B-Chemical
+type	I-Chemical
+-	I-Chemical
+1	I-Chemical
+receptor	I-Chemical
+antagonist	I-Chemical
+SR48692	B-Chemical
+blocked	O
+both	O
+the	O
+behavioral	O
+and	O
+the	O
+electrophysiological	O
+effects	O
+induced	O
+by	O
+neurotensin	B-Chemical
+.	O
+
+CONCLUSION	O
+:	O
+Activation	O
+of	O
+pallidal	O
+neurotensin	B-Chemical
+receptors	O
+may	O
+be	O
+involved	O
+in	O
+neurotensin	B-Chemical
+-	O
+induced	O
+antiparkinsonian	O
+effects	O
+.	O
+
+Carmofur	B-Chemical
+-	O
+induced	O
+organic	B-Disease
+mental	I-Disease
+disorders	I-Disease
+.	O
+
+Organic	B-Disease
+mental	I-Disease
+disorder	I-Disease
+was	O
+observed	O
+in	O
+a	O
+29	O
+-	O
+year	O
+-	O
+old	O
+female	O
+in	O
+the	O
+prognostic	O
+period	O
+after	O
+the	O
+onset	O
+of	O
+carmofur	B-Chemical
+-	O
+induced	O
+leukoencephalopathy	B-Disease
+.	O
+
+Symptoms	O
+such	O
+as	O
+euphoria	O
+,	O
+emotional	O
+lability	O
+and	O
+puerile	O
+attitude	O
+noted	O
+in	O
+the	O
+patient	O
+were	O
+diagnosed	O
+as	O
+organic	B-Disease
+personality	I-Disease
+syndrome	I-Disease
+according	O
+to	O
+the	O
+criteria	O
+defined	O
+in	O
+the	O
+DSM	O
+-	O
+III	O
+-	O
+R	O
+.	O
+
+It	O
+is	O
+referred	O
+to	O
+as	O
+a	O
+frontal	B-Disease
+lobe	I-Disease
+syndrome	I-Disease
+.	O
+
+Brain	O
+CT	O
+revealed	O
+a	O
+periventricular	O
+low	O
+density	O
+area	O
+in	O
+the	O
+frontal	O
+white	O
+matter	O
+and	O
+moderate	O
+dilatation	O
+of	O
+the	O
+lateral	O
+ventricles	O
+especially	O
+at	O
+the	O
+bilateral	O
+anterior	O
+horns	O
+.	O
+
+Consequently	O
+,	O
+carmofur	B-Chemical
+-	O
+induced	O
+leukoencephalopathy	B-Disease
+may	O
+uncommonly	O
+result	O
+in	O
+organic	B-Disease
+personality	I-Disease
+syndrome	I-Disease
+in	O
+the	O
+residual	O
+state	O
+.	O
+
+It	O
+may	O
+be	O
+attributed	O
+to	O
+the	O
+structural	B-Disease
+damage	I-Disease
+to	I-Disease
+the	I-Disease
+frontal	I-Disease
+lobe	I-Disease
+.	O
+
+Butyrylcholinesterase	O
+gene	O
+mutations	O
+in	O
+patients	O
+with	O
+prolonged	O
+apnea	B-Disease
+after	O
+succinylcholine	B-Chemical
+for	O
+electroconvulsive	O
+therapy	O
+.	O
+
+BACKGROUND	O
+:	O
+patients	O
+undergoing	O
+electroconvulsive	O
+therapy	O
+(	O
+ECT	O
+)	O
+often	O
+receive	O
+succinylcholine	B-Chemical
+as	O
+part	O
+of	O
+the	O
+anesthetic	O
+procedure	O
+.	O
+
+The	O
+duration	O
+of	O
+action	O
+may	O
+be	O
+prolonged	O
+in	O
+patients	O
+with	O
+genetic	O
+variants	O
+of	O
+the	O
+butyrylcholinesterase	O
+enzyme	O
+(	O
+BChE	O
+)	O
+,	O
+the	O
+most	O
+common	O
+being	O
+the	O
+K	O
+-	O
+and	O
+the	O
+A	O
+-	O
+variants	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+assess	O
+the	O
+clinical	O
+significance	O
+of	O
+genetic	O
+variants	O
+in	O
+butyrylcholinesterase	O
+gene	O
+(	O
+BCHE	O
+)	O
+in	O
+patients	O
+with	O
+a	O
+suspected	O
+prolonged	O
+duration	O
+of	O
+action	O
+of	O
+succinylcholine	B-Chemical
+after	O
+ECT	O
+.	O
+
+METHODS	O
+:	O
+a	O
+total	O
+of	O
+13	O
+patients	O
+were	O
+referred	O
+to	O
+the	O
+Danish	O
+Cholinesterase	O
+Research	O
+Unit	O
+after	O
+ECT	O
+during	O
+38	O
+months	O
+.	O
+
+We	O
+determined	O
+the	O
+BChE	O
+activity	O
+and	O
+the	O
+BCHE	O
+genotype	O
+using	O
+molecular	O
+genetic	O
+methods	O
+,	O
+the	O
+duration	O
+of	O
+apnea	B-Disease
+,	O
+time	O
+to	O
+sufficient	O
+spontaneous	O
+ventilation	O
+and	O
+whether	O
+neuromuscular	O
+monitoring	O
+was	O
+used	O
+.	O
+
+The	O
+duration	O
+of	O
+apnea	B-Disease
+was	O
+compared	O
+with	O
+published	O
+data	O
+on	O
+normal	O
+subjects	O
+.	O
+
+RESULTS	O
+:	O
+in	O
+11	O
+patients	O
+,	O
+mutations	O
+were	O
+found	O
+in	O
+the	O
+BCHE	O
+gene	O
+,	O
+the	O
+K	O
+-	O
+variant	O
+being	O
+the	O
+most	O
+frequent	O
+.	O
+
+The	O
+duration	O
+of	O
+apnea	B-Disease
+was	O
+5	O
+-	O
+15	O
+min	O
+compared	O
+with	O
+3	O
+-	O
+5	O
+.	O
+3	O
+min	O
+from	O
+the	O
+literature	O
+.	O
+
+Severe	O
+distress	O
+was	O
+noted	O
+in	O
+the	O
+recovery	O
+phase	O
+in	O
+two	O
+patients	O
+.	O
+
+Neuromuscular	O
+monitoring	O
+was	O
+used	O
+in	O
+two	O
+patients	O
+.	O
+
+CONCLUSION	O
+:	O
+eleven	O
+of	O
+13	O
+patients	O
+with	O
+a	O
+prolonged	O
+duration	O
+of	O
+action	O
+of	O
+succinylcholine	B-Chemical
+had	O
+mutations	O
+in	O
+BCHE	O
+,	O
+indicating	O
+that	O
+this	O
+is	O
+the	O
+possible	O
+reason	O
+for	O
+a	O
+prolonged	O
+period	O
+of	O
+apnea	B-Disease
+.	O
+
+We	O
+recommend	O
+objective	O
+neuromuscular	O
+monitoring	O
+during	O
+the	O
+first	O
+ECT	O
+.	O
+
+Perhexiline	B-Chemical
+maleate	I-Chemical
+and	O
+peripheral	B-Disease
+neuropathy	I-Disease
+.	O
+
+Peripheral	B-Disease
+neuropathy	I-Disease
+has	O
+been	O
+noted	O
+as	O
+a	O
+complication	O
+of	O
+therapy	O
+with	O
+perhexiline	B-Chemical
+maleate	I-Chemical
+,	O
+a	O
+drug	O
+widely	O
+used	O
+in	O
+France	O
+(	O
+and	O
+in	O
+clinical	O
+trials	O
+in	O
+the	O
+United	O
+States	O
+)	O
+for	O
+the	O
+prophylactic	O
+treatment	O
+of	O
+angina	B-Disease
+pectoris	I-Disease
+.	O
+
+In	O
+24	O
+patients	O
+with	O
+this	O
+complication	O
+,	O
+the	O
+marked	O
+slowing	O
+of	O
+motor	O
+nerve	O
+conduction	O
+velocity	O
+and	O
+the	O
+electromyographic	O
+changes	O
+imply	O
+mainly	O
+a	O
+demyelinating	B-Disease
+disorder	I-Disease
+.	O
+
+Improvement	O
+was	O
+noted	O
+with	O
+cessation	O
+of	O
+therapy	O
+.	O
+
+In	O
+a	O
+few	O
+cases	O
+the	O
+presence	O
+of	O
+active	O
+denervation	O
+signified	O
+a	O
+poor	O
+prognosis	O
+,	O
+with	O
+only	O
+slight	O
+improvement	O
+.	O
+
+The	O
+underlying	O
+mechanism	O
+causing	O
+the	O
+neuropathy	B-Disease
+is	O
+not	O
+yet	O
+fully	O
+known	O
+,	O
+although	O
+some	O
+evidence	O
+indicates	O
+that	O
+it	O
+may	O
+be	O
+a	O
+lipid	O
+storage	O
+process	O
+.	O
+
+A	O
+phase	O
+I	O
+study	O
+of	O
+4	B-Chemical
+'	I-Chemical
+-	I-Chemical
+0	I-Chemical
+-	I-Chemical
+tetrahydropyranyladriamycin	I-Chemical
+.	O
+
+Clinical	O
+pharmacology	O
+and	O
+pharmacokinetics	O
+.	O
+
+A	O
+Phase	O
+I	O
+study	O
+of	O
+intravenous	O
+(	O
+IV	O
+)	O
+bolus	O
+4	B-Chemical
+'	I-Chemical
+-	I-Chemical
+0	I-Chemical
+-	I-Chemical
+tetrahydropyranyladriamycin	I-Chemical
+(	O
+Pirarubicin	B-Chemical
+)	O
+was	O
+done	O
+in	O
+55	O
+patients	O
+in	O
+good	O
+performance	O
+status	O
+with	O
+refractory	O
+tumors	B-Disease
+.	O
+
+Twenty	O
+-	O
+six	O
+had	O
+minimal	O
+prior	O
+therapy	O
+(	O
+good	O
+risk	O
+)	O
+,	O
+23	O
+had	O
+extensive	O
+prior	O
+therapy	O
+(	O
+poor	O
+risk	O
+)	O
+,	O
+and	O
+six	O
+had	O
+renal	B-Disease
+and	I-Disease
+/	I-Disease
+or	I-Disease
+hepatic	I-Disease
+dysfunction	I-Disease
+.	O
+
+A	O
+total	O
+of	O
+167	O
+courses	O
+at	O
+doses	O
+of	O
+15	O
+to	O
+70	O
+mg	O
+/	O
+m2	O
+were	O
+evaluable	O
+.	O
+
+Maximum	O
+tolerated	O
+dose	O
+in	O
+good	O
+-	O
+risk	O
+patients	O
+was	O
+70	O
+mg	O
+/	O
+m2	O
+,	O
+and	O
+in	O
+poor	O
+-	O
+risk	O
+patients	O
+,	O
+60	O
+mg	O
+/	O
+m2	O
+.	O
+
+The	O
+dose	O
+-	O
+limiting	O
+toxic	O
+effect	O
+was	O
+transient	O
+noncumulative	O
+granulocytopenia	B-Disease
+.	O
+
+Granulocyte	O
+nadir	O
+was	O
+on	O
+day	O
+14	O
+(	O
+range	O
+,	O
+4	O
+-	O
+22	O
+)	O
+.	O
+
+Less	O
+frequent	O
+toxic	O
+effects	O
+included	O
+thrombocytopenia	B-Disease
+,	O
+anemia	B-Disease
+,	O
+nausea	B-Disease
+,	O
+mild	O
+alopecia	B-Disease
+,	O
+phlebitis	B-Disease
+,	O
+and	O
+mucositis	B-Disease
+.	O
+
+Myelosuppression	B-Disease
+was	O
+more	O
+in	O
+patients	O
+with	O
+hepatic	B-Disease
+dysfunction	I-Disease
+.	O
+
+Pharmacokinetic	O
+analyses	O
+in	O
+21	O
+patients	O
+revealed	O
+Pirarubicin	B-Chemical
+plasma	O
+T	O
+1	O
+/	O
+2	O
+alpha	O
+(	O
++	O
+/	O
+-	O
+SE	O
+)	O
+of	O
+2	O
+.	O
+5	O
++	O
+/	O
+-	O
+0	O
+.	O
+85	O
+minutes	O
+,	O
+T	O
+beta	O
+1	O
+/	O
+2	O
+of	O
+25	O
+.	O
+6	O
++	O
+/	O
+-	O
+6	O
+.	O
+5	O
+minutes	O
+,	O
+and	O
+T	O
+1	O
+/	O
+2	O
+gamma	O
+of	O
+23	O
+.	O
+6	O
++	O
+/	O
+-	O
+7	O
+.	O
+6	O
+hours	O
+.	O
+
+The	O
+area	O
+under	O
+the	O
+curve	O
+was	O
+537	O
++	O
+/	O
+-	O
+149	O
+ng	O
+/	O
+ml	O
+x	O
+hours	O
+,	O
+volume	O
+of	O
+distribution	O
+(	O
+Vd	O
+)	O
+3504	O
++	O
+/	O
+-	O
+644	O
+l	O
+/	O
+m2	O
+,	O
+and	O
+total	O
+clearance	O
+(	O
+ClT	O
+)	O
+was	O
+204	O
++	O
+39	O
+.	O
+3	O
+l	O
+/	O
+hour	O
+/	O
+m2	O
+.	O
+
+Adriamycinol	B-Chemical
+,	O
+doxorubicin	B-Chemical
+,	O
+adriamycinone	B-Chemical
+,	O
+and	O
+tetrahydropyranyladriamycinol	B-Chemical
+were	O
+the	O
+metabolites	O
+detected	O
+in	O
+plasma	O
+and	O
+the	O
+amount	O
+of	O
+doxorubicin	B-Chemical
+was	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+10	O
+%	O
+of	O
+the	O
+total	O
+metabolites	O
+.	O
+
+Urinary	O
+excretion	O
+of	O
+Pirarubicin	B-Chemical
+in	O
+the	O
+first	O
+24	O
+hours	O
+was	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+10	O
+%	O
+.	O
+
+Activity	O
+was	O
+noted	O
+in	O
+mesothelioma	B-Disease
+,	O
+leiomyosarcoma	B-Disease
+,	O
+and	O
+basal	B-Disease
+cell	I-Disease
+carcinoma	I-Disease
+.	O
+
+The	O
+recommended	O
+starting	O
+dose	O
+for	O
+Phase	O
+II	O
+trials	O
+is	O
+60	O
+mg	O
+/	O
+m2	O
+IV	O
+bolus	O
+every	O
+3	O
+weeks	O
+.	O
+
+Ocular	B-Disease
+and	I-Disease
+auditory	I-Disease
+toxicity	I-Disease
+in	O
+hemodialyzed	O
+patients	O
+receiving	O
+desferrioxamine	B-Chemical
+.	O
+
+During	O
+an	O
+18	O
+-	O
+month	O
+period	O
+of	O
+study	O
+41	O
+hemodialyzed	O
+patients	O
+receiving	O
+desferrioxamine	B-Chemical
+(	O
+10	O
+-	O
+40	O
+mg	O
+/	O
+kg	O
+BW	O
+/	O
+3	O
+times	O
+weekly	O
+)	O
+for	O
+the	O
+first	O
+time	O
+were	O
+monitored	O
+for	O
+detection	O
+of	O
+audiovisual	B-Disease
+toxicity	I-Disease
+.	O
+
+6	O
+patients	O
+presented	O
+clinical	O
+symptoms	O
+of	O
+visual	B-Disease
+or	I-Disease
+auditory	I-Disease
+toxicity	I-Disease
+.	O
+
+Moreover	O
+,	O
+detailed	O
+ophthalmologic	O
+and	O
+audiologic	O
+studies	O
+disclosed	O
+abnormalities	O
+in	O
+7	O
+more	O
+asymptomatic	O
+patients	O
+.	O
+
+Visual	B-Disease
+toxicity	I-Disease
+was	O
+of	O
+retinal	O
+origin	O
+and	O
+was	O
+characterized	O
+by	O
+a	O
+tritan	O
+-	O
+type	O
+dyschromatopsy	B-Disease
+,	O
+sometimes	O
+associated	O
+with	O
+a	B-Disease
+loss	I-Disease
+of	I-Disease
+visual	I-Disease
+acuity	I-Disease
+and	O
+pigmentary	B-Disease
+retinal	I-Disease
+deposits	I-Disease
+.	O
+
+Auditory	B-Disease
+toxicity	I-Disease
+was	O
+characterized	O
+by	O
+a	O
+mid	O
+-	O
+to	O
+high	O
+-	O
+frequency	O
+neurosensorial	B-Disease
+hearing	I-Disease
+loss	I-Disease
+and	O
+the	O
+lesion	O
+was	O
+of	O
+the	O
+cochlear	O
+type	O
+.	O
+
+Desferrioxamine	B-Chemical
+withdrawal	O
+resulted	O
+in	O
+a	O
+complete	O
+recovery	O
+of	O
+visual	O
+function	O
+in	O
+1	O
+patient	O
+and	O
+partial	O
+recovery	O
+in	O
+3	O
+,	O
+and	O
+a	O
+complete	O
+reversal	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+in	O
+3	O
+patients	O
+and	O
+partial	O
+recovery	O
+in	O
+3	O
+.	O
+
+This	O
+toxicity	B-Disease
+appeared	O
+in	O
+patients	O
+receiving	O
+the	O
+higher	O
+doses	O
+of	O
+desferrioxamine	B-Chemical
+or	O
+coincided	O
+with	O
+the	O
+normalization	O
+of	O
+ferritin	O
+or	O
+aluminium	B-Chemical
+serum	O
+levels	O
+.	O
+
+The	O
+data	O
+indicate	O
+that	O
+audiovisual	B-Disease
+toxicity	I-Disease
+is	O
+not	O
+an	O
+infrequent	O
+complication	O
+in	O
+hemodialyzed	O
+patients	O
+receiving	O
+desferrioxamine	B-Chemical
+.	O
+
+Periodical	O
+audiovisual	O
+monitoring	O
+should	O
+be	O
+performed	O
+on	O
+hemodialyzed	O
+patients	O
+receiving	O
+the	O
+drug	O
+in	O
+order	O
+to	O
+detect	O
+adverse	O
+effects	O
+as	O
+early	O
+as	O
+possible	O
+.	O
+
+Serial	O
+epilepsy	B-Disease
+caused	O
+by	O
+levodopa	B-Chemical
+/	I-Chemical
+carbidopa	I-Chemical
+administration	O
+in	O
+two	O
+patients	O
+on	O
+hemodialysis	O
+.	O
+
+Two	O
+patients	O
+with	O
+similar	O
+clinical	O
+features	O
+are	O
+presented	O
+:	O
+both	O
+patients	O
+had	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+,	O
+on	O
+hemodialysis	O
+for	O
+many	O
+years	O
+but	O
+recently	O
+begun	O
+on	O
+a	O
+high	O
+-	O
+flux	O
+dialyzer	O
+;	O
+both	O
+had	O
+been	O
+receiving	O
+a	O
+carbidopa	B-Chemical
+/	I-Chemical
+levodopa	I-Chemical
+preparation	O
+;	O
+and	O
+both	O
+had	O
+the	O
+onset	O
+of	O
+hallucinosis	B-Disease
+and	O
+recurrent	O
+seizures	B-Disease
+,	O
+which	O
+were	O
+refractory	O
+to	O
+anticonvulsants	O
+.	O
+
+The	O
+first	O
+patient	O
+died	O
+without	O
+a	O
+diagnosis	O
+;	O
+the	O
+second	O
+patient	O
+had	O
+a	O
+dramatic	O
+recovery	O
+following	O
+the	O
+administration	O
+of	O
+vitamin	B-Chemical
+B6	I-Chemical
+.	O
+
+Neither	O
+patient	O
+was	O
+considered	O
+to	O
+have	O
+a	O
+renal	O
+state	O
+sufficiently	O
+severe	O
+enough	O
+to	O
+explain	O
+their	O
+presentation	O
+.	O
+
+Randomized	O
+,	O
+double	O
+-	O
+blind	O
+trial	O
+of	O
+mazindol	B-Chemical
+in	O
+Duchenne	B-Disease
+dystrophy	I-Disease
+.	O
+
+There	O
+is	O
+evidence	O
+that	O
+growth	O
+hormone	O
+may	O
+be	O
+related	O
+to	O
+the	O
+progression	O
+of	O
+weakness	B-Disease
+in	O
+Duchenne	B-Disease
+dystrophy	I-Disease
+.	O
+
+We	O
+conducted	O
+a	O
+12	O
+-	O
+month	O
+controlled	O
+trial	O
+of	O
+mazindol	B-Chemical
+,	O
+a	O
+putative	O
+growth	O
+hormone	O
+secretion	O
+inhibitor	O
+,	O
+in	O
+83	O
+boys	O
+with	O
+Duchenne	B-Disease
+dystrophy	I-Disease
+.	O
+
+Muscle	O
+strength	O
+,	O
+contractures	O
+,	O
+functional	O
+ability	O
+and	O
+pulmonary	O
+function	O
+were	O
+tested	O
+at	O
+baseline	O
+,	O
+and	O
+6	O
+and	O
+12	O
+months	O
+after	O
+treatment	O
+with	O
+mazindol	B-Chemical
+(	O
+3	O
+mg	O
+/	O
+d	O
+)	O
+or	O
+placebo	O
+.	O
+
+The	O
+study	O
+was	O
+designed	O
+to	O
+have	O
+a	O
+power	O
+of	O
+greater	O
+than	O
+0	O
+.	O
+90	O
+to	O
+detect	O
+a	O
+slowing	O
+to	O
+25	O
+%	O
+of	O
+the	O
+expected	O
+rate	O
+of	O
+progression	O
+of	O
+weakness	B-Disease
+at	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+.	O
+
+Mazindol	B-Chemical
+did	O
+not	O
+benefit	O
+strength	O
+at	O
+any	O
+point	O
+in	O
+the	O
+study	O
+.	O
+
+Side	O
+effects	O
+attributable	O
+to	O
+mazindol	B-Chemical
+included	O
+decreased	B-Disease
+appetite	I-Disease
+(	O
+36	O
+%	O
+)	O
+,	O
+dry	B-Disease
+mouth	I-Disease
+(	O
+10	O
+%	O
+)	O
+,	O
+behavioral	O
+change	O
+(	O
+22	O
+%	O
+)	O
+,	O
+and	O
+gastrointestinal	B-Disease
+symptoms	I-Disease
+(	O
+18	O
+%	O
+)	O
+;	O
+mazindol	B-Chemical
+dosage	O
+was	O
+reduced	O
+in	O
+43	O
+%	O
+of	O
+patients	O
+.	O
+
+The	O
+effect	O
+of	O
+mazindol	B-Chemical
+on	O
+GH	O
+secretion	O
+was	O
+estimated	O
+indirectly	O
+by	O
+comparing	O
+the	O
+postabsorptive	O
+IGF	O
+-	O
+I	O
+levels	O
+obtained	O
+following	O
+3	O
+,	O
+6	O
+,	O
+9	O
+,	O
+and	O
+12	O
+months	O
+in	O
+the	O
+mazindol	B-Chemical
+treated	O
+to	O
+those	O
+in	O
+the	O
+placebo	O
+groups	O
+.	O
+
+Although	O
+mazindol	B-Chemical
+-	O
+treated	O
+patients	O
+gained	O
+less	O
+weight	O
+and	O
+height	O
+than	O
+placebo	O
+-	O
+treated	O
+patients	O
+,	O
+no	O
+significant	O
+effect	O
+on	O
+IGF	O
+-	O
+I	O
+levels	O
+was	O
+observed	O
+.	O
+
+Mazindol	B-Chemical
+doses	O
+not	O
+slow	O
+the	O
+progression	O
+of	O
+weakness	B-Disease
+in	O
+Duchenne	B-Disease
+dystrophy	I-Disease
+.	O
+
+Facilitation	O
+of	O
+memory	O
+retrieval	O
+by	O
+pre	O
+-	O
+test	O
+morphine	B-Chemical
+and	O
+its	O
+state	O
+dependency	O
+in	O
+the	O
+step	O
+-	O
+through	O
+type	O
+passive	O
+avoidance	O
+learning	O
+test	O
+in	O
+mice	O
+.	O
+
+Amnesia	B-Disease
+produced	O
+by	O
+scopolamine	B-Chemical
+and	O
+cycloheximide	B-Chemical
+were	O
+reversed	O
+by	O
+morphine	B-Chemical
+given	O
+30	O
+min	O
+before	O
+the	O
+test	O
+trial	O
+(	O
+pre	O
+-	O
+test	O
+)	O
+,	O
+and	O
+pre	O
+-	O
+test	O
+morphine	B-Chemical
+also	O
+facilitated	O
+the	O
+memory	O
+retrieval	O
+in	O
+the	O
+animals	O
+administered	O
+naloxone	B-Chemical
+during	O
+the	O
+training	O
+trial	O
+.	O
+
+Similarly	O
+,	O
+pre	O
+-	O
+test	O
+scopolamine	B-Chemical
+partially	O
+reversed	O
+the	O
+scopolamine	B-Chemical
+-	O
+induced	O
+amnesia	B-Disease
+,	O
+but	O
+not	O
+significantly	O
+;	O
+and	O
+pre	O
+-	O
+test	O
+cycloheximide	B-Chemical
+failed	O
+to	O
+reverse	O
+the	O
+cycloheximide	B-Chemical
+-	O
+induced	O
+amnesia	B-Disease
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+the	O
+facilitation	O
+of	O
+memory	O
+retrieval	O
+by	O
+pre	O
+-	O
+test	O
+morphine	B-Chemical
+might	O
+be	O
+the	O
+direct	O
+action	O
+of	O
+morphine	B-Chemical
+rather	O
+than	O
+a	O
+state	O
+dependent	O
+effect	O
+.	O
+
+Naloxone	B-Chemical
+reverses	O
+the	O
+antihypertensive	O
+effect	O
+of	O
+clonidine	B-Chemical
+.	O
+
+In	O
+unanesthetized	O
+,	O
+spontaneously	O
+hypertensive	B-Disease
+rats	O
+the	O
+decrease	O
+in	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+produced	O
+by	O
+intravenous	O
+clonidine	B-Chemical
+,	O
+5	O
+to	O
+20	O
+micrograms	O
+/	O
+kg	O
+,	O
+was	O
+inhibited	O
+or	O
+reversed	O
+by	O
+nalozone	B-Chemical
+,	O
+0	O
+.	O
+2	O
+to	O
+2	O
+mg	O
+/	O
+kg	O
+.	O
+
+The	O
+hypotensive	B-Disease
+effect	O
+of	O
+100	O
+mg	O
+/	O
+kg	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+was	O
+also	O
+partially	O
+reversed	O
+by	O
+naloxone	B-Chemical
+.	O
+
+Naloxone	B-Chemical
+alone	O
+did	O
+not	O
+affect	O
+either	O
+blood	O
+pressure	O
+or	O
+heart	O
+rate	O
+.	O
+
+In	O
+brain	O
+membranes	O
+from	O
+spontaneously	O
+hypertensive	B-Disease
+rats	O
+clonidine	B-Chemical
+,	O
+10	O
+(	O
+-	O
+8	O
+)	O
+to	O
+10	O
+(	O
+-	O
+5	O
+)	O
+M	O
+,	O
+did	O
+not	O
+influence	O
+stereoselective	O
+binding	O
+of	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+naloxone	I-Chemical
+(	O
+8	O
+nM	O
+)	O
+,	O
+and	O
+naloxone	B-Chemical
+,	O
+10	O
+(	O
+-	O
+8	O
+)	O
+to	O
+10	O
+(	O
+-	O
+4	O
+)	O
+M	O
+,	O
+did	O
+not	O
+influence	O
+clonidine	B-Chemical
+-	O
+suppressible	O
+binding	O
+of	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+dihydroergocryptine	I-Chemical
+(	O
+1	O
+nM	O
+)	O
+.	O
+
+These	O
+findings	O
+indicate	O
+that	O
+in	O
+spontaneously	O
+hypertensive	B-Disease
+rats	O
+the	O
+effects	O
+of	O
+central	O
+alpha	O
+-	O
+adrenoceptor	O
+stimulation	O
+involve	O
+activation	O
+of	O
+opiate	O
+receptors	O
+.	O
+
+As	O
+naloxone	B-Chemical
+and	O
+clonidine	B-Chemical
+do	O
+not	O
+appear	O
+to	O
+interact	O
+with	O
+the	O
+same	O
+receptor	O
+site	O
+,	O
+the	O
+observed	O
+functional	O
+antagonism	O
+suggests	O
+the	O
+release	O
+of	O
+an	O
+endogenous	O
+opiate	O
+by	O
+clonidine	B-Chemical
+or	O
+alpha	B-Chemical
+-	I-Chemical
+methyldopa	I-Chemical
+and	O
+the	O
+possible	O
+role	O
+of	O
+the	O
+opiate	O
+in	O
+the	O
+central	O
+control	O
+of	O
+sympathetic	O
+tone	O
+.	O
+
+Neurotoxicity	B-Disease
+of	O
+halogenated	B-Chemical
+hydroxyquinolines	I-Chemical
+:	O
+clinical	O
+analysis	O
+of	O
+cases	O
+reported	O
+outside	O
+Japan	O
+.	O
+
+An	O
+analysis	O
+is	O
+presented	O
+of	O
+220	O
+cases	O
+of	O
+possible	O
+neurotoxic	B-Disease
+reactions	O
+to	O
+halogenated	B-Chemical
+hydroxyquinolines	I-Chemical
+reported	O
+from	O
+outside	O
+Japan	O
+.	O
+
+In	O
+80	O
+cases	O
+insufficient	O
+information	O
+was	O
+available	O
+for	O
+adequate	O
+comment	O
+and	O
+in	O
+29	O
+a	O
+relationship	O
+to	O
+the	O
+administration	O
+of	O
+clioquinol	B-Chemical
+could	O
+be	O
+excluded	O
+.	O
+
+Of	O
+the	O
+remainder	O
+,	O
+a	O
+relationship	O
+to	O
+clioquinol	B-Chemical
+was	O
+considered	O
+probable	O
+in	O
+42	O
+and	O
+possible	O
+in	O
+69	O
+cases	O
+.	O
+
+In	O
+six	O
+of	O
+the	O
+probable	O
+cases	O
+the	O
+neurological	B-Disease
+disturbance	I-Disease
+consisted	O
+of	O
+an	O
+acute	O
+reversible	O
+encephalopathy	B-Disease
+usually	O
+related	O
+to	O
+the	O
+ingestion	O
+of	O
+a	O
+high	O
+dose	O
+of	O
+clioquinol	B-Chemical
+over	O
+a	O
+short	O
+period	O
+.	O
+
+The	O
+most	O
+common	O
+manifestation	O
+,	O
+observed	O
+in	O
+15	O
+further	O
+cases	O
+,	O
+was	O
+isolated	O
+optic	B-Disease
+atrophy	I-Disease
+.	O
+
+This	O
+was	O
+most	O
+frequently	O
+found	O
+in	O
+children	O
+,	O
+many	O
+of	O
+whom	O
+had	O
+received	O
+clioquinol	B-Chemical
+as	O
+treatment	O
+for	O
+acrodermatitis	B-Disease
+enteropathica	I-Disease
+.	O
+
+In	O
+the	O
+remaining	O
+cases	O
+,	O
+a	O
+combination	O
+of	O
+myelopathy	B-Disease
+,	O
+visual	B-Disease
+disturbance	I-Disease
+,	O
+and	O
+peripheral	B-Disease
+neuropathy	I-Disease
+was	O
+the	O
+most	O
+common	O
+manifestation	O
+.	O
+
+Isolated	O
+myelopathy	B-Disease
+or	O
+peripheral	B-Disease
+neuropathy	I-Disease
+,	O
+or	O
+these	O
+manifestations	O
+occurring	O
+together	O
+,	O
+were	O
+infrequent	O
+.	O
+
+The	O
+onset	O
+of	O
+all	O
+manifestations	O
+(	O
+except	O
+toxic	O
+encephalopathy	B-Disease
+)	O
+was	O
+usually	O
+subacute	O
+,	O
+with	O
+subsequent	O
+partial	O
+recovery	O
+.	O
+
+Older	O
+subjects	O
+tended	O
+to	O
+display	O
+more	O
+side	O
+effects	O
+.	O
+
+The	O
+full	O
+syndrome	O
+of	O
+subacute	O
+myelo	B-Disease
+-	I-Disease
+optic	I-Disease
+neuropathy	I-Disease
+was	O
+more	O
+frequent	O
+in	O
+women	O
+,	O
+but	O
+they	O
+tended	O
+to	O
+have	O
+taken	O
+greater	O
+quantities	O
+of	O
+the	O
+drug	O
+.	O
+
+Prazosin	B-Chemical
+-	O
+induced	O
+stress	B-Disease
+incontinence	I-Disease
+.	O
+
+A	O
+case	O
+of	O
+genuine	O
+stress	B-Disease
+incontinence	I-Disease
+due	O
+to	O
+prazosin	B-Chemical
+,	O
+a	O
+common	O
+antihypertensive	O
+drug	O
+,	O
+is	O
+presented	O
+.	O
+
+Prazosin	B-Chemical
+exerts	O
+its	O
+antihypertensive	O
+effects	O
+through	O
+vasodilatation	O
+caused	O
+by	O
+selective	O
+blockade	O
+of	O
+postsynaptic	O
+alpha	O
+-	O
+1	O
+adrenergic	O
+receptors	O
+.	O
+
+As	O
+an	O
+alpha	O
+-	O
+blocker	O
+,	O
+it	O
+also	O
+exerts	O
+a	O
+significant	O
+relaxant	O
+effect	O
+on	O
+the	O
+bladder	O
+neck	O
+and	O
+urethra	O
+.	O
+
+The	O
+patient	O
+'	O
+s	O
+clinical	O
+course	O
+is	O
+described	O
+and	O
+correlated	O
+with	O
+initial	O
+urodynamic	O
+studies	O
+while	O
+on	O
+prazosin	B-Chemical
+and	O
+subsequent	O
+studies	O
+while	O
+taking	O
+verapamil	B-Chemical
+.	O
+
+Her	O
+incontinence	B-Disease
+resolved	O
+with	O
+the	O
+change	O
+of	O
+medication	O
+.	O
+
+The	O
+restoration	O
+of	O
+continence	O
+was	O
+accompanied	O
+by	O
+a	O
+substantial	O
+rise	O
+in	O
+maximum	O
+urethral	O
+pressure	O
+,	O
+maximum	O
+urethral	O
+closure	O
+pressure	O
+,	O
+and	O
+functional	O
+urethral	O
+length	O
+.	O
+
+Patients	O
+who	O
+present	O
+with	O
+stress	B-Disease
+incontinence	I-Disease
+while	O
+taking	O
+prazosin	B-Chemical
+should	O
+change	O
+their	O
+antihypertensive	O
+medication	O
+before	O
+considering	O
+surgery	O
+,	O
+because	O
+their	O
+incontinence	B-Disease
+may	O
+resolve	O
+spontaneously	O
+with	O
+a	O
+change	O
+in	O
+drug	O
+therapy	O
+.	O
+
+Myocardial	B-Disease
+infarction	I-Disease
+following	O
+sublingual	O
+administration	O
+of	O
+isosorbide	B-Chemical
+dinitrate	I-Chemical
+.	O
+
+A	O
+78	O
+-	O
+year	O
+-	O
+old	O
+with	O
+healed	O
+septal	O
+necrosis	B-Disease
+suffered	O
+a	O
+recurrent	O
+myocardial	B-Disease
+infarction	I-Disease
+of	O
+the	O
+anterior	O
+wall	O
+following	O
+the	O
+administration	O
+of	O
+isosorbide	B-Chemical
+dinitrate	I-Chemical
+5	O
+mg	O
+sublingually	O
+.	O
+
+After	O
+detailing	O
+the	O
+course	O
+of	O
+events	O
+,	O
+we	O
+discuss	O
+the	O
+role	O
+of	O
+paradoxical	O
+coronary	O
+spasm	B-Disease
+and	O
+hypotension	B-Disease
+-	O
+mediated	O
+myocardial	B-Disease
+ischemia	I-Disease
+occurring	O
+downstream	O
+to	O
+significant	O
+coronary	B-Disease
+arterial	I-Disease
+stenosis	I-Disease
+in	O
+the	O
+pathophysiology	O
+of	O
+acute	B-Disease
+coronary	I-Disease
+insufficiency	I-Disease
+.	O
+
+Comparison	O
+of	O
+the	O
+respiratory	O
+effects	O
+of	O
+i	O
+.	O
+v	O
+.	O
+infusions	O
+of	O
+morphine	B-Chemical
+and	O
+regional	O
+analgesia	O
+by	O
+extradural	O
+block	O
+.	O
+
+The	O
+incidence	O
+of	O
+postoperative	O
+respiratory	O
+apnoea	B-Disease
+was	O
+compared	O
+between	O
+five	O
+patients	O
+receiving	O
+a	O
+continuous	O
+i	O
+.	O
+v	O
+.	O
+infusion	O
+of	O
+morphine	B-Chemical
+(	O
+mean	O
+73	O
+.	O
+6	O
+mg	O
+)	O
+and	O
+five	O
+patients	O
+receiving	O
+a	O
+continuous	O
+extradural	O
+infusion	O
+of	O
+0	O
+.	O
+25	O
+%	O
+bupivacaine	B-Chemical
+(	O
+mean	O
+192	O
+mg	O
+)	O
+in	O
+the	O
+24	O
+-	O
+h	O
+period	O
+following	O
+upper	O
+abdominal	O
+surgery	O
+.	O
+
+Monitoring	O
+consisted	O
+of	O
+airflow	O
+detection	O
+by	O
+a	O
+carbon	B-Chemical
+dioxide	I-Chemical
+analyser	O
+,	O
+chest	O
+wall	O
+movement	O
+detected	O
+by	O
+pneumatic	O
+capsules	O
+,	O
+and	O
+continuous	O
+electrocardiograph	O
+recorded	O
+with	O
+a	O
+Holter	O
+ambulatory	O
+monitor	O
+.	O
+
+Both	O
+obstructive	B-Disease
+(	I-Disease
+P	I-Disease
+less	I-Disease
+than	I-Disease
+0	I-Disease
+.	I-Disease
+05	I-Disease
+)	I-Disease
+and	I-Disease
+central	I-Disease
+apnoea	I-Disease
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+occurred	O
+more	O
+frequently	O
+in	O
+patients	O
+who	O
+had	O
+a	O
+morphine	B-Chemical
+infusion	O
+.	O
+
+There	O
+was	O
+also	O
+a	O
+higher	O
+incidence	O
+of	O
+tachyarrhythmias	B-Disease
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+ventricular	B-Disease
+ectopic	I-Disease
+beats	I-Disease
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+in	O
+the	O
+morphine	B-Chemical
+infusion	O
+group	O
+.	O
+
+Effects	O
+of	O
+aminophylline	B-Chemical
+on	O
+the	O
+threshold	O
+for	O
+initiating	O
+ventricular	B-Disease
+fibrillation	I-Disease
+during	O
+respiratory	B-Disease
+failure	I-Disease
+.	O
+
+Cardiac	B-Disease
+arrhythmias	I-Disease
+have	O
+frequently	O
+been	O
+reported	O
+in	O
+association	O
+with	O
+respiratory	B-Disease
+failure	I-Disease
+.	O
+
+The	O
+possible	O
+additive	O
+role	O
+of	O
+pharmacologic	O
+agents	O
+in	O
+precipitating	O
+cardiac	B-Disease
+disturbances	I-Disease
+in	O
+patients	O
+with	O
+respiratory	B-Disease
+failure	I-Disease
+has	O
+only	O
+recently	O
+been	O
+emphasized	O
+.	O
+
+The	O
+effects	O
+of	O
+aminophylline	B-Chemical
+on	O
+the	O
+ventricular	B-Disease
+fibrillation	I-Disease
+threshold	O
+during	O
+normal	O
+acid	O
+-	O
+base	O
+conditions	O
+and	O
+during	O
+respiratory	B-Disease
+failure	I-Disease
+were	O
+studied	O
+in	O
+anesthetized	O
+open	O
+chest	O
+dogs	O
+.	O
+
+The	O
+ventricular	B-Disease
+fibrillation	I-Disease
+threshold	O
+was	O
+measured	O
+by	O
+passing	O
+a	O
+gated	O
+train	O
+of	O
+12	O
+constant	O
+current	O
+pulses	O
+through	O
+the	O
+ventricular	O
+myocardium	O
+during	O
+the	O
+vulnerable	O
+period	O
+of	O
+the	O
+cardiac	O
+cycle	O
+.	O
+
+During	O
+the	O
+infusion	O
+of	O
+aminophylline	B-Chemical
+,	O
+the	O
+ventricular	B-Disease
+fibrillation	I-Disease
+threshold	O
+was	O
+reduced	O
+by	O
+30	O
+to	O
+40	O
+percent	O
+of	O
+the	O
+control	O
+when	O
+pH	O
+and	O
+partial	O
+pressures	O
+of	O
+oxygen	B-Chemical
+(	O
+PO2	B-Chemical
+)	O
+and	O
+carbon	B-Chemical
+dioxide	I-Chemical
+(	O
+CO2	B-Chemical
+)	O
+were	O
+kept	O
+within	O
+normal	O
+limits	O
+.	O
+
+When	O
+respiratory	B-Disease
+failure	I-Disease
+was	O
+produced	O
+by	O
+hypoventilation	B-Disease
+(	O
+pH	O
+7	O
+.	O
+05	O
+to	O
+7	O
+.	O
+25	O
+;	O
+PC02	O
+70	O
+to	O
+100	O
+mm	O
+Hg	O
+:	O
+P02	O
+20	O
+to	O
+40	O
+mm	O
+Hg	O
+)	O
+,	O
+infusion	O
+of	O
+aminophylline	B-Chemical
+resulted	O
+in	O
+an	O
+even	O
+greater	O
+decrease	O
+in	O
+ventricular	B-Disease
+fibrillation	I-Disease
+threshold	O
+to	O
+60	O
+percent	O
+of	O
+the	O
+control	O
+level	O
+.	O
+
+These	O
+experiments	O
+suggest	O
+that	O
+although	O
+many	O
+factors	O
+may	O
+contribute	O
+to	O
+the	O
+increased	O
+incidence	O
+of	O
+ventricular	B-Disease
+arrhythmias	I-Disease
+in	O
+respiratory	B-Disease
+failure	I-Disease
+,	O
+pharmacologic	O
+agents	O
+,	O
+particularly	O
+aminophylline	B-Chemical
+,	O
+may	O
+play	O
+a	O
+significant	O
+role	O
+.	O
+
+Pentoxifylline	B-Chemical
+(	O
+Trental	B-Chemical
+)	O
+does	O
+not	O
+inhibit	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+coronary	O
+hyperemia	B-Disease
+:	O
+implications	O
+for	O
+dipyridamole	B-Chemical
+-	O
+thallium	B-Chemical
+-	O
+201	O
+myocardial	O
+imaging	O
+.	O
+
+Dipyridamole	B-Chemical
+-	O
+thallium	B-Chemical
+-	O
+201	O
+imaging	O
+is	O
+often	O
+performed	O
+in	O
+patients	O
+unable	O
+to	O
+exercise	O
+because	O
+of	O
+peripheral	B-Disease
+vascular	I-Disease
+disease	I-Disease
+.	O
+
+Many	O
+of	O
+these	O
+patients	O
+are	O
+taking	O
+pentoxifylline	B-Chemical
+(	O
+Trental	B-Chemical
+)	O
+,	O
+a	O
+methylxanthine	B-Chemical
+derivative	O
+which	O
+may	O
+improve	O
+intermittent	B-Disease
+claudication	I-Disease
+.	O
+
+Whether	O
+pentoxifylline	B-Chemical
+inhibits	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+coronary	O
+hyperemia	B-Disease
+like	O
+other	O
+methylxanthines	B-Chemical
+such	O
+as	O
+theophylline	B-Chemical
+and	O
+should	O
+be	O
+stopped	O
+prior	O
+to	O
+dipyridamole	B-Chemical
+-	O
+thallium	B-Chemical
+-	O
+201	O
+imaging	O
+is	O
+unknown	O
+.	O
+
+Therefore	O
+,	O
+we	O
+studied	O
+the	O
+hyperemic	O
+response	O
+to	O
+dipyridamole	B-Chemical
+in	O
+seven	O
+open	O
+-	O
+chest	O
+anesthetized	O
+dogs	O
+after	O
+pretreatment	O
+with	O
+either	O
+pentoxifylline	B-Chemical
+(	O
+0	O
+,	O
+7	O
+.	O
+5	O
+,	O
+or	O
+15	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+or	O
+theophylline	B-Chemical
+(	O
+3	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+.	O
+
+Baseline	O
+circumflex	O
+coronary	O
+blood	O
+flows	O
+did	O
+not	O
+differ	O
+significantly	O
+among	O
+treatment	O
+groups	O
+.	O
+
+Dipyridamole	B-Chemical
+significantly	O
+increased	O
+coronary	O
+blood	O
+flow	O
+before	O
+and	O
+after	O
+7	O
+.	O
+5	O
+or	O
+15	O
+mm	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+pentoxifylline	B-Chemical
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+Neither	O
+dose	O
+of	O
+pentoxifylline	B-Chemical
+significantly	O
+decreased	O
+the	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+hyperemia	B-Disease
+,	O
+while	O
+peak	O
+coronary	O
+blood	O
+flow	O
+was	O
+significantly	O
+lower	O
+after	O
+theophylline	B-Chemical
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+We	O
+conclude	O
+that	O
+pentoxyifylline	B-Chemical
+does	O
+not	O
+inhibit	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+coronary	O
+hyperemia	B-Disease
+even	O
+at	O
+high	O
+doses	O
+.	O
+
+Cause	O
+of	O
+death	B-Disease
+among	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+:	O
+a	O
+rare	O
+mortality	O
+due	O
+to	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+.	O
+
+Causes	O
+of	O
+death	B-Disease
+,	O
+with	O
+special	O
+reference	O
+to	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+,	O
+among	O
+240	O
+patients	O
+with	O
+pathologically	O
+verified	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+were	O
+investigated	O
+using	O
+the	O
+Annuals	O
+of	O
+the	O
+Pathological	O
+Autopsy	O
+Cases	O
+in	O
+Japan	O
+from	O
+1981	O
+to	O
+1985	O
+.	O
+
+The	O
+leading	O
+causes	O
+of	O
+death	B-Disease
+were	O
+pneumonia	B-Disease
+and	O
+bronchitis	B-Disease
+(	O
+44	O
+.	O
+1	O
+%	O
+)	O
+,	O
+malignant	O
+neoplasms	B-Disease
+(	O
+11	O
+.	O
+6	O
+%	O
+)	O
+,	O
+heart	B-Disease
+diseases	I-Disease
+(	O
+4	O
+.	O
+1	O
+%	O
+)	O
+,	O
+cerebral	B-Disease
+infarction	I-Disease
+(	O
+3	O
+.	O
+7	O
+%	O
+)	O
+and	O
+septicaemia	B-Disease
+(	O
+3	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+Cerebral	B-Disease
+haemorrhage	I-Disease
+was	O
+the	O
+11th	O
+most	O
+frequent	O
+cause	O
+of	O
+death	B-Disease
+,	O
+accounting	O
+for	O
+only	O
+0	O
+.	O
+8	O
+%	O
+of	O
+deaths	B-Disease
+among	O
+the	O
+patients	O
+,	O
+whereas	O
+it	O
+was	O
+the	O
+5th	O
+most	O
+common	O
+cause	O
+of	O
+death	B-Disease
+among	O
+the	O
+Japanese	O
+general	O
+population	O
+in	O
+1985	O
+.	O
+
+The	O
+low	O
+incidence	O
+of	O
+cerebral	B-Disease
+haemorrhage	I-Disease
+as	O
+a	O
+cause	O
+of	O
+death	B-Disease
+in	O
+patients	O
+with	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+may	O
+reflect	O
+the	O
+hypotensive	B-Disease
+effect	O
+of	O
+levodopa	B-Chemical
+and	O
+a	O
+hypotensive	B-Disease
+mechanism	O
+due	O
+to	O
+reduced	O
+noradrenaline	B-Chemical
+levels	O
+in	O
+the	O
+parkinsonian	B-Disease
+brain	O
+.	O
+
+Possible	O
+intramuscular	O
+midazolam	B-Chemical
+-	O
+associated	O
+cardiorespiratory	B-Disease
+arrest	I-Disease
+and	O
+death	B-Disease
+.	O
+
+Midazolam	B-Chemical
+hydrochloride	I-Chemical
+is	O
+commonly	O
+used	O
+for	O
+dental	O
+or	O
+endoscopic	O
+procedures	O
+.	O
+
+Although	O
+generally	O
+consisted	O
+safe	O
+when	O
+given	O
+intramuscularly	O
+,	O
+intravenous	O
+administration	O
+is	O
+known	O
+to	O
+cause	O
+respiratory	B-Disease
+and	I-Disease
+cardiovascular	I-Disease
+depression	I-Disease
+.	O
+
+This	O
+report	O
+describes	O
+the	O
+first	O
+published	O
+case	O
+of	O
+cardiorespiratory	B-Disease
+arrest	I-Disease
+and	O
+death	B-Disease
+associated	O
+with	O
+intramuscular	O
+administration	O
+of	O
+midazolam	B-Chemical
+.	O
+
+Information	O
+regarding	O
+midazolam	B-Chemical
+use	O
+is	O
+reviewed	O
+to	O
+provide	O
+recommendation	O
+for	O
+safe	O
+administration	O
+.	O
+
+Myasthenia	B-Disease
+gravis	I-Disease
+presenting	O
+as	O
+weakness	O
+after	O
+magnesium	B-Chemical
+administration	O
+.	O
+
+We	O
+studied	O
+a	O
+patient	O
+with	O
+no	O
+prior	O
+history	O
+of	O
+neuromuscular	B-Disease
+disease	I-Disease
+who	O
+became	O
+virtually	O
+quadriplegic	B-Disease
+after	O
+parenteral	O
+magnesium	B-Chemical
+administration	O
+for	O
+preeclampsia	B-Disease
+.	O
+
+The	O
+serum	O
+magnesium	B-Chemical
+concentration	O
+was	O
+3	O
+.	O
+0	O
+mEq	O
+/	O
+L	O
+,	O
+which	O
+is	O
+usually	O
+well	O
+tolerated	O
+.	O
+
+The	O
+magnesium	B-Chemical
+was	O
+stopped	O
+and	O
+she	O
+recovered	O
+over	O
+a	O
+few	O
+days	O
+.	O
+
+While	O
+she	O
+was	O
+weak	O
+,	O
+2	O
+-	O
+Hz	O
+repetitive	O
+stimulation	O
+revealed	O
+a	O
+decrement	O
+without	O
+significant	O
+facilitation	O
+at	O
+rapid	O
+rates	O
+or	O
+after	O
+exercise	O
+,	O
+suggesting	O
+postsynaptic	B-Disease
+neuromuscular	I-Disease
+blockade	I-Disease
+.	O
+
+After	O
+her	O
+strength	O
+returned	O
+,	O
+repetitive	O
+stimulation	O
+was	O
+normal	O
+,	O
+but	O
+single	O
+fiber	O
+EMG	O
+revealed	O
+increased	O
+jitter	O
+and	O
+blocking	O
+.	O
+
+Her	O
+acetylcholine	B-Chemical
+receptor	O
+antibody	O
+level	O
+was	O
+markedly	O
+elevated	O
+.	O
+
+Although	O
+paralysis	B-Disease
+after	O
+magnesium	B-Chemical
+administration	O
+has	O
+been	O
+described	O
+in	O
+patients	O
+with	O
+known	O
+myasthenia	B-Disease
+gravis	I-Disease
+,	O
+it	O
+has	O
+not	O
+previously	O
+been	O
+reported	O
+to	O
+be	O
+the	O
+initial	O
+or	O
+only	O
+manifestation	O
+of	O
+the	O
+disease	O
+.	O
+
+Patients	O
+who	O
+are	O
+unusually	O
+sensitive	O
+to	O
+the	O
+neuromuscular	O
+effects	O
+of	O
+magnesium	B-Chemical
+should	O
+be	O
+suspected	O
+of	O
+having	O
+an	O
+underlying	O
+disorder	B-Disease
+of	I-Disease
+neuromuscular	I-Disease
+transmission	I-Disease
+.	O
+
+No	O
+enhancement	O
+by	O
+phenobarbital	B-Chemical
+of	O
+the	O
+hepatocarcinogenicity	O
+of	O
+a	O
+choline	B-Chemical
+-	O
+devoid	O
+diet	O
+in	O
+the	O
+rat	O
+.	O
+
+An	O
+experiment	O
+was	O
+performed	O
+to	O
+test	O
+whether	O
+inclusion	O
+of	O
+phenobarbital	B-Chemical
+in	O
+a	O
+choline	B-Chemical
+-	O
+devoid	O
+diet	O
+would	O
+increase	O
+the	O
+hepatocarcinogenicity	O
+of	O
+the	O
+diet	O
+.	O
+
+Groups	O
+of	O
+5	O
+-	O
+week	O
+old	O
+male	O
+Fischer	O
+-	O
+344	O
+rats	O
+were	O
+fed	O
+for	O
+7	O
+-	O
+25	O
+months	O
+semipurified	O
+choline	B-Chemical
+-	O
+devoid	O
+or	O
+choline	B-Chemical
+-	O
+supplemented	O
+diets	O
+,	O
+containing	O
+or	O
+not	O
+0	O
+.	O
+06	O
+%	O
+phenobarbital	B-Chemical
+.	O
+
+No	O
+hepatic	O
+preneoplastic	O
+nodules	O
+or	O
+hepatocellular	B-Disease
+carcinomas	I-Disease
+developed	O
+in	O
+rats	O
+fed	O
+the	O
+plain	O
+choline	B-Chemical
+-	O
+supplemented	O
+diet	O
+,	O
+while	O
+one	O
+preneoplastic	O
+nodule	O
+and	O
+one	O
+hepatocellular	B-Disease
+carcinoma	I-Disease
+developed	O
+in	O
+two	O
+rats	O
+fed	O
+the	O
+same	O
+diet	O
+containing	O
+phenobarbital	B-Chemical
+.	O
+
+The	O
+incidence	O
+of	O
+preneoplastic	O
+nodules	O
+and	O
+of	O
+hepatocellular	B-Disease
+carcinomas	I-Disease
+was	O
+10	O
+%	O
+and	O
+37	O
+%	O
+,	O
+respectively	O
+,	O
+in	O
+rats	O
+fed	O
+the	O
+plain	O
+choline	B-Chemical
+-	O
+devoid	O
+diet	O
+,	O
+and	O
+17	O
+%	O
+and	O
+30	O
+%	O
+,	O
+in	O
+rats	O
+fed	O
+the	O
+phenobarbital	B-Chemical
+-	O
+containing	O
+choline	B-Chemical
+-	O
+devoid	O
+diet	O
+.	O
+
+The	O
+results	O
+evinced	O
+no	O
+enhancement	O
+of	O
+the	O
+hepatocarcinogenicity	O
+of	O
+the	O
+choline	B-Chemical
+-	O
+devoid	O
+diet	O
+by	O
+phenobarbital	B-Chemical
+.	O
+
+Sporadic	O
+neoplastic	O
+lesions	O
+were	O
+observed	O
+in	O
+organs	O
+other	O
+than	O
+the	O
+liver	O
+of	O
+some	O
+of	O
+the	O
+animals	O
+,	O
+irrespective	O
+of	O
+the	O
+diet	O
+fed	O
+.	O
+
+On	O
+two	O
+paradoxical	O
+side	O
+-	O
+effects	O
+of	O
+prednisolone	B-Chemical
+in	O
+rats	O
+,	O
+ribosomal	O
+RNA	O
+biosyntheses	O
+,	O
+and	O
+a	O
+mechanism	O
+of	O
+action	O
+.	O
+
+Liver	B-Disease
+enlargement	I-Disease
+and	O
+muscle	B-Disease
+wastage	I-Disease
+occurred	O
+in	O
+Wistar	O
+rats	O
+following	O
+the	O
+subcutaneous	O
+administration	O
+of	O
+prednisolone	B-Chemical
+.	O
+
+In	O
+the	O
+liver	O
+both	O
+the	O
+content	O
+of	O
+RNA	O
+and	O
+the	O
+biosynthesis	O
+of	O
+ribosomal	O
+RNA	O
+increased	O
+while	O
+both	O
+the	O
+RNA	O
+content	O
+and	O
+ribosomal	O
+RNA	O
+biosynthesis	O
+were	O
+reduced	O
+in	O
+the	O
+gastrocnemius	O
+muscle	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+the	O
+drug	O
+acted	O
+in	O
+a	O
+selective	O
+and	O
+tissue	O
+-	O
+specific	O
+manner	O
+to	O
+enhance	O
+ribosomal	O
+RNA	O
+synthesis	O
+in	O
+the	O
+liver	O
+and	O
+depress	O
+such	O
+synthesis	O
+in	O
+the	O
+muscle	O
+.	O
+
+This	O
+view	O
+supports	O
+the	O
+contention	O
+that	O
+the	O
+liver	O
+and	O
+muscle	O
+are	O
+independent	O
+sites	O
+of	O
+prednisolone	B-Chemical
+action	O
+.	O
+
+Differential	O
+effects	O
+of	O
+gamma	B-Chemical
+-	I-Chemical
+hexachlorocyclohexane	I-Chemical
+(	O
+lindane	B-Chemical
+)	O
+on	O
+pharmacologically	O
+-	O
+induced	O
+seizures	B-Disease
+.	O
+
+Gamma	B-Chemical
+-	I-Chemical
+hexachlorocyclohexane	I-Chemical
+(	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+)	O
+,	O
+the	O
+active	O
+ingredient	O
+of	O
+the	O
+insecticide	O
+lindane	B-Chemical
+,	O
+has	O
+been	O
+shown	O
+to	O
+decrease	O
+seizure	B-Disease
+threshold	O
+to	O
+pentylenetrazol	O
+(	O
+PTZ	B-Chemical
+)	O
+3	O
+h	O
+after	O
+exposure	O
+to	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+and	O
+conversely	O
+increase	O
+threshold	O
+to	O
+PTZ	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+24	O
+h	O
+after	O
+exposure	O
+to	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+(	O
+Vohland	O
+et	O
+al	O
+.	O
+1981	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+severity	O
+of	O
+response	O
+to	O
+other	O
+seizure	B-Disease
+-	O
+inducing	O
+agents	O
+was	O
+tested	O
+in	O
+mice	O
+1	O
+and	O
+24	O
+h	O
+after	O
+intraperitoneal	O
+administration	O
+of	O
+80	O
+mg	O
+/	O
+kg	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+.	O
+
+One	O
+hour	O
+after	O
+the	O
+administration	O
+of	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+,	O
+the	O
+activity	O
+of	O
+seizure	B-Disease
+-	O
+inducing	O
+agents	O
+was	O
+increased	O
+,	O
+regardless	O
+of	O
+their	O
+mechanism	O
+,	O
+while	O
+24	O
+h	O
+after	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+a	O
+differential	O
+response	O
+was	O
+observed	O
+.	O
+
+Seizure	B-Disease
+activity	O
+due	O
+to	O
+PTZ	B-Chemical
+and	O
+picrotoxin	B-Chemical
+(	O
+PTX	B-Chemical
+)	O
+was	O
+significantly	O
+decreased	O
+;	O
+however	O
+,	O
+seizure	B-Disease
+activity	O
+due	O
+to	O
+3	B-Chemical
+-	I-Chemical
+mercaptopropionic	I-Chemical
+acid	I-Chemical
+(	O
+MPA	B-Chemical
+)	O
+,	O
+bicuculline	B-Chemical
+(	O
+BCC	B-Chemical
+)	O
+,	O
+methyl	B-Chemical
+6	I-Chemical
+,	I-Chemical
+7	I-Chemical
+-	I-Chemical
+dimethoxy	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+ethyl	I-Chemical
+-	I-Chemical
+B	I-Chemical
+-	I-Chemical
+carboline	I-Chemical
+-	I-Chemical
+3	I-Chemical
+-	I-Chemical
+carboxylate	I-Chemical
+(	O
+DMCM	B-Chemical
+)	O
+,	O
+or	O
+strychnine	B-Chemical
+(	O
+STR	B-Chemical
+)	O
+was	O
+not	O
+different	O
+from	O
+control	O
+.	O
+
+In	O
+vitro	O
+,	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+,	O
+pentylenetetrazol	B-Chemical
+and	O
+picrotoxin	B-Chemical
+were	O
+shown	O
+to	O
+inhibit	O
+3H	B-Chemical
+-	I-Chemical
+TBOB	I-Chemical
+binding	O
+in	O
+mouse	O
+whole	O
+brain	O
+,	O
+with	O
+IC50	O
+values	O
+of	O
+4	O
+.	O
+6	O
+,	O
+404	O
+and	O
+9	O
+.	O
+4	O
+microM	O
+,	O
+respectively	O
+.	O
+
+MPA	B-Chemical
+,	O
+BCC	B-Chemical
+,	O
+DMCM	B-Chemical
+,	O
+and	O
+STR	B-Chemical
+showed	O
+no	O
+inhibition	O
+of	O
+3H	B-Chemical
+-	I-Chemical
+TBOB	I-Chemical
+(	O
+t	B-Chemical
+-	I-Chemical
+butyl	I-Chemical
+bicyclo	I-Chemical
+-	I-Chemical
+orthobenzoate	I-Chemical
+)	O
+binding	O
+at	O
+concentrations	O
+of	O
+100	O
+micron	O
+.	O
+
+The	O
+pharmacological	O
+challenge	O
+data	O
+suggest	O
+that	O
+tolerance	O
+may	O
+occur	O
+to	O
+seizure	B-Disease
+activity	O
+induced	O
+by	O
+PTZ	B-Chemical
+and	O
+PTX	B-Chemical
+24	O
+h	O
+after	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+,	O
+since	O
+the	O
+response	O
+to	O
+only	O
+these	O
+two	O
+seizure	B-Disease
+-	O
+inducing	O
+agents	O
+is	O
+decreased	O
+.	O
+
+The	O
+in	O
+vitro	O
+data	O
+suggest	O
+that	O
+the	O
+site	O
+responsible	O
+for	O
+the	O
+decrease	O
+in	O
+seizure	B-Disease
+activity	O
+24	O
+h	O
+after	O
+gamma	B-Chemical
+-	I-Chemical
+HCH	I-Chemical
+may	O
+be	O
+the	O
+GABA	B-Chemical
+-	O
+A	O
+receptor	O
+-	O
+linked	O
+chloride	O
+channel	O
+.	O
+
+Tolerance	O
+and	O
+antiviral	O
+effect	O
+of	O
+ribavirin	B-Chemical
+in	O
+patients	O
+with	O
+Argentine	B-Disease
+hemorrhagic	I-Disease
+fever	I-Disease
+.	O
+
+Tolerance	O
+and	O
+antiviral	O
+effect	O
+of	O
+ribavirin	B-Chemical
+was	O
+studied	O
+in	O
+6	O
+patients	O
+with	O
+Argentine	B-Disease
+hemorrhagic	I-Disease
+fever	I-Disease
+(	O
+AHF	B-Disease
+)	O
+of	O
+more	O
+than	O
+8	O
+days	O
+of	O
+evolution	O
+.	O
+
+Administration	O
+of	O
+ribavirin	B-Chemical
+resulted	O
+in	O
+a	O
+neutralization	O
+of	O
+viremia	B-Disease
+and	O
+a	O
+drop	O
+of	O
+endogenous	O
+interferon	O
+titers	O
+.	O
+
+The	O
+average	O
+time	O
+of	O
+death	B-Disease
+was	O
+delayed	O
+.	O
+
+A	O
+reversible	O
+anemia	B-Disease
+was	O
+the	O
+only	O
+adverse	O
+effect	O
+observed	O
+.	O
+
+From	O
+these	O
+results	O
+,	O
+we	O
+conclude	O
+that	O
+ribavirin	B-Chemical
+has	O
+an	O
+antiviral	O
+effect	O
+in	O
+advanced	O
+cases	O
+of	O
+AHF	B-Disease
+,	O
+and	O
+that	O
+anemia	B-Disease
+,	O
+the	O
+only	O
+secondary	O
+reaction	O
+observed	O
+,	O
+can	O
+be	O
+easily	O
+managed	O
+.	O
+
+The	O
+possible	O
+beneficial	O
+effect	O
+of	O
+ribavirin	B-Chemical
+during	O
+the	O
+initial	O
+days	O
+of	O
+AHF	B-Disease
+is	O
+discussed	O
+.	O
+
+Is	O
+the	O
+treatment	O
+of	O
+scabies	B-Disease
+hazardous	O
+?	O
+
+Treatment	O
+for	O
+scabies	B-Disease
+is	O
+usually	O
+initiated	O
+by	O
+general	O
+practitioners	O
+;	O
+most	O
+consider	O
+lindane	B-Chemical
+(	O
+gamma	B-Chemical
+benzene	I-Chemical
+hexachloride	I-Chemical
+)	O
+the	O
+treatment	O
+of	O
+choice	O
+.	O
+
+Lindane	B-Chemical
+is	O
+also	O
+widely	O
+used	O
+as	O
+an	O
+agricultural	O
+and	O
+industrial	O
+pesticide	O
+,	O
+and	O
+as	O
+a	O
+result	O
+the	O
+toxic	O
+profile	O
+of	O
+this	O
+insecticide	O
+is	O
+well	O
+understood	O
+.	O
+
+Evidence	O
+is	O
+accumulating	O
+that	O
+lindane	B-Chemical
+can	O
+be	O
+toxic	B-Disease
+to	I-Disease
+the	I-Disease
+central	I-Disease
+nervous	I-Disease
+system	I-Disease
+and	O
+may	O
+be	O
+associated	O
+with	O
+aplastic	B-Disease
+anaemia	I-Disease
+.	O
+
+Preparations	O
+containing	O
+lindane	B-Chemical
+continue	O
+to	O
+be	O
+sold	O
+over	O
+the	O
+counter	O
+and	O
+may	O
+represent	O
+a	O
+hazard	O
+to	O
+poorly	O
+informed	O
+patients	O
+.	O
+
+This	O
+literature	O
+review	O
+suggests	O
+that	O
+general	O
+practitioners	O
+should	O
+prescribe	O
+scabicides	O
+with	O
+increased	O
+caution	O
+for	O
+certain	O
+at	O
+-	O
+risk	O
+groups	O
+,	O
+and	O
+give	O
+adequate	O
+warnings	O
+regarding	O
+potential	O
+toxicity	B-Disease
+.	O
+
+Mouse	O
+strain	O
+-	O
+dependent	O
+effect	O
+of	O
+amantadine	B-Chemical
+on	O
+motility	O
+and	O
+brain	O
+biogenic	O
+amines	B-Chemical
+.	O
+
+The	O
+effect	O
+of	O
+amantadine	B-Chemical
+hydrochloride	I-Chemical
+,	O
+injected	O
+i	O
+.	O
+p	O
+.	O
+in	O
+6	O
+increments	O
+of	O
+100	O
+mg	O
+/	O
+kg	O
+each	O
+over	O
+30	O
+hr	O
+,	O
+on	O
+mouse	O
+motility	O
+and	O
+whole	O
+brain	O
+content	O
+of	O
+selected	O
+biogenic	O
+amines	B-Chemical
+and	O
+major	O
+metabolites	O
+was	O
+studied	O
+in	O
+4	O
+strains	O
+of	O
+mice	O
+.	O
+
+These	O
+were	O
+the	O
+albino	O
+Sprague	O
+-	O
+Dawley	O
+ICR	O
+and	O
+BALB	O
+/	O
+C	O
+,	O
+the	O
+black	O
+C57BL	O
+/	O
+6	O
+and	O
+the	O
+brown	O
+CDF	O
+-	O
+I	O
+mouse	O
+strains	O
+.	O
+
+Amantadine	B-Chemical
+treatment	O
+produced	O
+a	O
+biphasic	O
+effect	O
+on	O
+mouse	O
+motility	O
+.	O
+
+The	O
+initial	O
+dose	O
+of	O
+amantadine	B-Chemical
+depressed	B-Disease
+locomotor	O
+activity	O
+in	O
+all	O
+mouse	O
+strains	O
+studied	O
+with	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+being	O
+the	O
+most	O
+sensitive	O
+.	O
+
+Subsequent	O
+amantadine	B-Chemical
+treatments	O
+produced	O
+enhancement	O
+of	O
+motility	O
+from	O
+corresponding	O
+control	O
+in	O
+all	O
+mouse	O
+strains	O
+with	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+being	O
+the	O
+least	O
+sensitive	O
+.	O
+
+The	O
+locomotor	O
+activity	O
+was	O
+decreased	O
+from	O
+corresponding	O
+controls	O
+in	O
+all	O
+strains	O
+studied	O
+,	O
+except	O
+for	O
+the	O
+ICR	O
+mice	O
+,	O
+during	O
+an	O
+overnight	O
+drug	O
+-	O
+free	O
+period	O
+following	O
+the	O
+fourth	O
+amantadine	B-Chemical
+treatment	O
+.	O
+
+Readministration	O
+of	O
+amantadine	B-Chemical
+,	O
+after	O
+a	O
+drug	O
+-	O
+free	O
+overnight	O
+period	O
+,	O
+increased	O
+motility	O
+from	O
+respective	O
+saline	O
+control	O
+in	O
+all	O
+strains	O
+with	O
+exception	O
+of	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+where	O
+suppression	B-Disease
+of	I-Disease
+motility	I-Disease
+occurred	O
+.	O
+
+Treatment	O
+with	O
+amantadine	B-Chemical
+did	O
+not	O
+alter	O
+whole	O
+brain	O
+dopamine	B-Chemical
+levels	O
+but	O
+decreased	O
+the	O
+amounts	O
+of	O
+3	B-Chemical
+,	I-Chemical
+4	I-Chemical
+-	I-Chemical
+dihydroxyphenylacetic	I-Chemical
+acid	I-Chemical
+in	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+compared	O
+to	O
+saline	O
+control	O
+.	O
+
+Conversely	O
+,	O
+brain	O
+normetanephrine	B-Chemical
+concentration	O
+was	O
+increased	O
+from	O
+saline	O
+control	O
+by	O
+amantadine	B-Chemical
+in	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+.	O
+
+The	O
+results	O
+suggest	O
+a	O
+strain	O
+-	O
+dependent	O
+effect	O
+of	O
+amantadine	B-Chemical
+on	O
+motility	O
+and	O
+indicate	O
+a	O
+differential	O
+response	O
+to	O
+the	O
+acute	O
+and	O
+multiple	O
+dose	O
+regimens	O
+used	O
+.	O
+
+The	O
+BALB	O
+/	O
+C	O
+mouse	O
+was	O
+the	O
+most	O
+sensitive	O
+strain	O
+and	O
+could	O
+serve	O
+as	O
+the	O
+strain	O
+of	O
+choice	O
+for	O
+evaluating	O
+the	O
+side	O
+effects	O
+of	O
+amantadine	B-Chemical
+.	O
+
+The	O
+biochemical	O
+results	O
+of	O
+brain	O
+biogenic	O
+amines	B-Chemical
+of	O
+BALB	O
+/	O
+C	O
+mouse	O
+strain	O
+suggest	O
+a	O
+probable	O
+decrease	O
+of	O
+catecholamine	B-Chemical
+turnover	O
+rate	O
+and	O
+/	O
+or	O
+metabolism	O
+by	O
+monoamine	O
+oxidase	O
+and	O
+a	O
+resulting	O
+increase	O
+in	O
+O	O
+-	O
+methylation	O
+of	O
+norepinephrine	B-Chemical
+which	O
+may	O
+account	O
+for	O
+a	O
+behavioral	B-Disease
+depression	I-Disease
+caused	O
+by	O
+amantadine	B-Chemical
+in	O
+the	O
+BALB	O
+/	O
+C	O
+mice	O
+.	O
+
+Chloroacetaldehyde	B-Chemical
+and	O
+its	O
+contribution	O
+to	O
+urotoxicity	O
+during	O
+treatment	O
+with	O
+cyclophosphamide	B-Chemical
+or	O
+ifosfamide	B-Chemical
+.	O
+
+An	O
+experimental	O
+study	O
+/	O
+short	O
+communication	O
+.	O
+
+Based	O
+on	O
+clinical	O
+data	O
+,	O
+indicating	O
+that	O
+chloroacetaldehyde	B-Chemical
+(	O
+CAA	B-Chemical
+)	O
+is	O
+an	O
+important	O
+metabolite	O
+of	O
+oxazaphosphorine	O
+cytostatics	O
+,	O
+an	O
+experimental	O
+study	O
+was	O
+carried	O
+out	O
+in	O
+order	O
+to	O
+elucidate	O
+the	O
+role	O
+of	O
+CAA	B-Chemical
+in	O
+the	O
+development	O
+of	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+.	O
+
+The	O
+data	O
+demonstrate	O
+that	O
+CAA	B-Chemical
+after	O
+i	O
+.	O
+v	O
+.	O
+administration	O
+does	O
+not	O
+contribute	O
+to	O
+bladder	B-Disease
+damage	I-Disease
+.	O
+
+When	O
+instilled	O
+directly	O
+into	O
+the	O
+bladder	O
+,	O
+CAA	B-Chemical
+exerts	O
+urotoxic	O
+effects	O
+,	O
+it	O
+is	O
+,	O
+however	O
+,	O
+susceptible	O
+to	O
+detoxification	O
+with	O
+mesna	B-Chemical
+.	O
+
+Source	O
+of	O
+pain	B-Disease
+and	O
+primitive	O
+dysfunction	O
+in	O
+migraine	B-Disease
+:	O
+an	O
+identical	O
+site	O
+?	O
+
+Twenty	O
+common	O
+migraine	B-Disease
+patients	O
+received	O
+a	O
+one	O
+sided	O
+frontotemporal	O
+application	O
+of	O
+nitroglycerin	B-Chemical
+(	O
+10	O
+patients	O
+)	O
+or	O
+placebo	O
+ointment	O
+(	O
+10	O
+patients	O
+)	O
+in	O
+a	O
+double	O
+blind	O
+study	O
+.	O
+
+Early	O
+onset	O
+migraine	B-Disease
+attacks	O
+were	O
+induced	O
+by	O
+nitroglycerin	B-Chemical
+in	O
+seven	O
+out	O
+of	O
+10	O
+patients	O
+versus	O
+no	O
+patient	O
+in	O
+the	O
+placebo	O
+group	O
+.	O
+
+Subsequently	O
+20	O
+migraine	B-Disease
+patients	O
+,	O
+who	O
+developed	O
+an	O
+early	O
+onset	O
+attack	O
+with	O
+frontotemporal	O
+nitroglycerin	B-Chemical
+,	O
+received	O
+the	O
+drug	O
+in	O
+a	O
+second	O
+induction	O
+test	O
+at	O
+other	O
+body	O
+areas	O
+.	O
+
+No	O
+early	O
+onset	O
+migraine	B-Disease
+was	O
+observed	O
+.	O
+
+Thus	O
+the	O
+migraine	B-Disease
+-	O
+inducing	O
+effect	O
+of	O
+nitroglycerin	B-Chemical
+seems	O
+to	O
+depend	O
+on	O
+direct	O
+stimulation	O
+of	O
+the	O
+habitual	O
+site	O
+of	O
+pain	B-Disease
+,	O
+suggesting	O
+that	O
+the	O
+frontotemporal	O
+region	O
+is	O
+of	O
+crucial	O
+importance	O
+in	O
+the	O
+development	O
+of	O
+a	O
+migraine	B-Disease
+crisis	O
+.	O
+
+This	O
+is	O
+not	O
+consistent	O
+with	O
+a	O
+CNS	O
+origin	O
+of	O
+migraine	B-Disease
+attack	O
+.	O
+
+Hypersensitivity	B-Disease
+to	O
+carbamazepine	B-Chemical
+presenting	O
+with	O
+a	O
+leukemoid	B-Disease
+reaction	I-Disease
+,	O
+eosinophilia	B-Disease
+,	O
+erythroderma	B-Disease
+,	O
+and	O
+renal	B-Disease
+failure	I-Disease
+.	O
+
+We	O
+report	O
+a	O
+patient	O
+in	O
+whom	O
+hypersensitivity	B-Disease
+to	O
+carbamazepine	B-Chemical
+presented	O
+with	O
+generalized	O
+erythroderma	B-Disease
+,	O
+a	O
+severe	O
+leukemoid	B-Disease
+reaction	I-Disease
+,	O
+eosinophilia	B-Disease
+,	O
+hyponatremia	B-Disease
+,	O
+and	O
+renal	B-Disease
+failure	I-Disease
+.	O
+
+This	O
+is	O
+the	O
+first	O
+report	O
+of	O
+such	O
+an	O
+unusual	O
+reaction	O
+to	O
+carbamazepine	B-Chemical
+.	O
+
+Fluoxetine	B-Chemical
+-	O
+induced	O
+akathisia	B-Disease
+:	O
+clinical	O
+and	O
+theoretical	O
+implications	O
+.	O
+
+Five	O
+patients	O
+receiving	O
+fluoxetine	B-Chemical
+for	O
+the	O
+treatment	O
+of	O
+obsessive	B-Disease
+compulsive	I-Disease
+disorder	I-Disease
+or	O
+major	B-Disease
+depression	I-Disease
+developed	O
+akathisia	B-Disease
+.	O
+
+The	O
+typical	O
+fluoxetine	B-Chemical
+-	O
+induced	O
+symptoms	O
+of	O
+restlessness	O
+,	O
+constant	O
+pacing	O
+,	O
+purposeless	O
+movements	O
+of	O
+the	O
+feet	O
+and	O
+legs	O
+,	O
+and	O
+marked	O
+anxiety	B-Disease
+were	O
+indistinguishable	O
+from	O
+those	O
+of	O
+neuroleptic	O
+-	O
+induced	O
+akathisia	B-Disease
+.	O
+
+Three	O
+patients	O
+who	O
+had	O
+experienced	O
+neuroleptic	O
+-	O
+induced	O
+akathisia	B-Disease
+in	O
+the	O
+past	O
+reported	O
+that	O
+the	O
+symptoms	O
+of	O
+fluoxetine	B-Chemical
+-	O
+induced	O
+akathisia	B-Disease
+were	O
+identical	O
+,	O
+although	O
+somewhat	O
+milder	O
+.	O
+
+Akathisia	B-Disease
+appeared	O
+to	O
+be	O
+a	O
+common	O
+side	O
+effect	O
+of	O
+fluoxetine	B-Chemical
+and	O
+generally	O
+responded	O
+well	O
+to	O
+treatment	O
+with	O
+the	O
+beta	O
+-	O
+adrenergic	O
+antagonist	O
+propranolol	B-Chemical
+,	O
+dose	O
+reduction	O
+,	O
+or	O
+both	O
+.	O
+
+The	O
+authors	O
+suggest	O
+that	O
+fluoxetine	B-Chemical
+-	O
+induced	O
+akathisia	B-Disease
+may	O
+be	O
+caused	O
+by	O
+serotonergically	O
+mediated	O
+inhibition	O
+of	O
+dopaminergic	O
+neurotransmission	O
+and	O
+that	O
+the	O
+pathophysiology	O
+of	O
+fluoxetine	B-Chemical
+-	O
+induced	O
+akathisia	B-Disease
+and	O
+tricyclic	O
+antidepressant	B-Chemical
+-	O
+induced	O
+"	O
+jitteriness	O
+"	O
+may	O
+be	O
+identical	O
+.	O
+
+Effect	O
+of	O
+converting	O
+enzyme	O
+inhibition	O
+on	O
+the	O
+course	O
+of	O
+adriamycin	B-Chemical
+-	O
+induced	O
+nephropathy	B-Disease
+.	O
+
+The	O
+effect	O
+of	O
+the	O
+converting	O
+enzyme	O
+inhibitor	O
+(	O
+CEI	O
+)	O
+enalapril	B-Chemical
+was	O
+assessed	O
+in	O
+Munich	O
+-	O
+Wistar	O
+rats	O
+with	O
+established	O
+adriamycin	B-Chemical
+nephrosis	B-Disease
+.	O
+
+Rats	O
+were	O
+given	O
+a	O
+single	O
+dose	O
+of	O
+adriamycin	B-Chemical
+and	O
+one	O
+month	O
+later	O
+divided	O
+into	O
+four	O
+groups	O
+matched	O
+for	O
+albuminuria	B-Disease
+,	O
+blood	O
+pressure	O
+,	O
+and	O
+plasma	O
+albumin	O
+concentration	O
+.	O
+
+Groups	O
+1	O
+and	O
+3	O
+remained	O
+untreated	O
+while	O
+groups	O
+2	O
+and	O
+4	O
+received	O
+enalapril	B-Chemical
+.	O
+
+Groups	O
+1	O
+and	O
+2	O
+underwent	O
+micropuncture	O
+studies	O
+after	O
+10	O
+days	O
+.	O
+
+These	O
+short	O
+-	O
+term	O
+studies	O
+showed	O
+that	O
+enalapril	B-Chemical
+reduced	O
+arterial	O
+blood	O
+pressure	O
+(	O
+101	O
++	O
+/	O
+-	O
+2	O
+vs	O
+.	O
+124	O
++	O
+/	O
+-	O
+3	O
+mm	O
+Hg	O
+,	O
+group	O
+2	O
+vs	O
+.	O
+1	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+glomerular	O
+capillary	O
+pressure	O
+(	O
+54	O
++	O
+/	O
+-	O
+1	O
+vs	O
+.	O
+61	O
++	O
+/	O
+-	O
+2	O
+mm	O
+Hg	O
+,	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+without	O
+reducing	O
+albuminuria	B-Disease
+(	O
+617	O
++	O
+/	O
+-	O
+50	O
+vs	O
+.	O
+570	O
++	O
+/	O
+-	O
+47	O
+mg	O
+/	O
+day	O
+)	O
+or	O
+GFR	O
+(	O
+1	O
+.	O
+03	O
++	O
+/	O
+-	O
+0	O
+.	O
+04	O
+vs	O
+.	O
+1	O
+.	O
+04	O
++	O
+/	O
+-	O
+0	O
+.	O
+11	O
+ml	O
+/	O
+min	O
+)	O
+.	O
+
+Groups	O
+3	O
+and	O
+4	O
+were	O
+studied	O
+at	O
+four	O
+and	O
+at	O
+six	O
+months	O
+to	O
+assess	O
+the	O
+effect	O
+of	O
+enalapril	B-Chemical
+on	O
+progression	O
+of	O
+renal	B-Disease
+injury	I-Disease
+in	O
+adriamycin	B-Chemical
+nephrosis	B-Disease
+.	O
+
+Chronic	O
+enalapril	B-Chemical
+treatment	O
+reduced	O
+blood	O
+pressure	O
+without	O
+reducing	O
+albuminuria	B-Disease
+in	O
+group	O
+4	O
+.	O
+
+Untreated	O
+group	O
+3	O
+rats	O
+exhibited	O
+a	O
+progressive	O
+reduction	O
+in	O
+GFR	O
+(	O
+0	O
+.	O
+35	O
++	O
+/	O
+-	O
+0	O
+.	O
+08	O
+ml	O
+/	O
+min	O
+at	O
+4	O
+months	O
+,	O
+0	O
+.	O
+27	O
++	O
+/	O
+-	O
+0	O
+.	O
+07	O
+ml	O
+/	O
+min	O
+at	O
+6	O
+months	O
+)	O
+.	O
+
+Enalapril	B-Chemical
+treatment	O
+blunted	O
+but	O
+did	O
+not	O
+prevent	O
+reduction	O
+in	O
+GFR	O
+in	O
+group	O
+4	O
+(	O
+0	O
+.	O
+86	O
++	O
+/	O
+-	O
+0	O
+.	O
+15	O
+ml	O
+/	O
+min	O
+at	O
+4	O
+months	O
+,	O
+0	O
+.	O
+69	O
++	O
+/	O
+-	O
+0	O
+.	O
+13	O
+ml	O
+/	O
+min	O
+at	O
+6	O
+months	O
+,	O
+both	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+vs	O
+.	O
+group	O
+3	O
+)	O
+.	O
+
+Reduction	O
+in	O
+GFR	O
+was	O
+associated	O
+with	O
+the	O
+development	O
+of	O
+glomerular	B-Disease
+sclerosis	I-Disease
+in	O
+both	O
+treated	O
+and	O
+untreated	O
+rats	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Clotiazepam	B-Chemical
+-	O
+induced	O
+acute	O
+hepatitis	B-Disease
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+patient	O
+who	O
+developed	O
+acute	O
+hepatitis	B-Disease
+with	O
+extensive	B-Disease
+hepatocellular	I-Disease
+necrosis	I-Disease
+,	O
+7	O
+months	O
+after	O
+the	O
+onset	O
+of	O
+administration	O
+of	O
+clotiazepam	B-Chemical
+,	O
+a	O
+thienodiazepine	B-Chemical
+derivative	O
+.	O
+
+Clotiazepam	B-Chemical
+withdrawal	O
+was	O
+followed	O
+by	O
+prompt	O
+recovery	O
+.	O
+
+The	O
+administration	O
+of	O
+several	O
+benzodiazepines	B-Chemical
+,	O
+chemically	O
+related	O
+to	O
+clotiazepam	B-Chemical
+,	O
+did	O
+not	O
+interfere	O
+with	O
+recovery	O
+and	O
+did	O
+not	O
+induce	O
+any	O
+relapse	O
+of	O
+hepatitis	B-Disease
+.	O
+
+This	O
+observation	O
+shows	O
+that	O
+clotiazepam	B-Chemical
+can	O
+induce	O
+acute	O
+hepatitis	B-Disease
+and	O
+suggests	O
+that	O
+there	O
+is	O
+no	O
+cross	O
+hepatotoxicity	B-Disease
+between	O
+clotiazepam	B-Chemical
+and	O
+several	O
+benzodiazepines	B-Chemical
+.	O
+
+5	B-Chemical
+-	I-Chemical
+azacytidine	I-Chemical
+potentiates	O
+initiation	B-Disease
+induced	I-Disease
+by	I-Disease
+carcinogens	I-Disease
+in	O
+rat	O
+liver	O
+.	O
+
+To	O
+test	O
+the	O
+validity	O
+of	O
+the	O
+hypothesis	O
+that	O
+hypomethylation	O
+of	O
+DNA	O
+plays	O
+an	O
+important	O
+role	O
+in	O
+the	O
+initiation	B-Disease
+of	I-Disease
+carcinogenic	I-Disease
+process	I-Disease
+,	O
+5	B-Chemical
+-	I-Chemical
+azacytidine	I-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+AzC	I-Chemical
+)	O
+(	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+an	O
+inhibitor	O
+of	O
+DNA	O
+methylation	O
+,	O
+was	O
+given	O
+to	O
+rats	O
+during	O
+the	O
+phase	O
+of	O
+repair	O
+synthesis	O
+induced	O
+by	O
+the	O
+three	O
+carcinogens	O
+,	O
+benzo	B-Chemical
+[	I-Chemical
+a	I-Chemical
+]	I-Chemical
+-	I-Chemical
+pyrene	I-Chemical
+(	O
+200	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+N	B-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+N	I-Chemical
+-	I-Chemical
+nitrosourea	I-Chemical
+(	O
+60	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+1	B-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+dimethylhydrazine	I-Chemical
+(	O
+1	B-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+DMH	I-Chemical
+)	O
+(	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+The	O
+initiated	O
+hepatocytes	O
+in	O
+the	O
+liver	O
+were	O
+assayed	O
+as	O
+the	O
+gamma	O
+-	O
+glutamyltransferase	O
+(	O
+gamma	O
+-	O
+GT	O
+)	O
+positive	O
+foci	O
+formed	O
+following	O
+a	O
+2	O
+-	O
+week	O
+selection	O
+regimen	O
+consisting	O
+of	O
+dietary	O
+0	O
+.	O
+02	O
+%	O
+2	B-Chemical
+-	I-Chemical
+acetylaminofluorene	I-Chemical
+coupled	O
+with	O
+a	O
+necrogenic	O
+dose	O
+of	O
+CCl4	B-Chemical
+.	O
+
+The	O
+results	O
+obtained	O
+indicate	O
+that	O
+with	O
+all	O
+three	O
+carcinogens	O
+,	O
+administration	O
+of	O
+5	B-Chemical
+-	I-Chemical
+AzC	I-Chemical
+during	O
+repair	O
+synthesis	O
+increased	O
+the	O
+incidence	O
+of	O
+initiated	O
+hepatocytes	O
+,	O
+for	O
+example	O
+10	O
+-	O
+20	O
+foci	O
+/	O
+cm2	O
+in	O
+5	B-Chemical
+-	I-Chemical
+AzC	I-Chemical
+and	O
+carcinogen	O
+-	O
+treated	O
+rats	O
+compared	O
+with	O
+3	O
+-	O
+5	O
+foci	O
+/	O
+cm2	O
+in	O
+rats	O
+treated	O
+with	O
+carcinogen	O
+only	O
+.	O
+
+Administration	O
+of	O
+[	B-Chemical
+3H	I-Chemical
+]	I-Chemical
+-	I-Chemical
+5	I-Chemical
+-	I-Chemical
+azadeoxycytidine	I-Chemical
+during	O
+the	O
+repair	O
+synthesis	O
+induced	O
+by	O
+1	B-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+DMH	I-Chemical
+further	O
+showed	O
+that	O
+0	O
+.	O
+019	O
+mol	O
+%	O
+of	O
+cytosine	B-Chemical
+residues	O
+in	O
+DNA	O
+were	O
+substituted	O
+by	O
+the	O
+analogue	O
+,	O
+indicating	O
+that	O
+incorporation	O
+of	O
+5	B-Chemical
+-	I-Chemical
+AzC	I-Chemical
+occurs	O
+during	O
+repair	O
+synthesis	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+the	O
+carcinogen	O
+,	O
+5	B-Chemical
+-	I-Chemical
+AzC	I-Chemical
+given	O
+after	O
+a	O
+two	O
+thirds	O
+partial	O
+hepatectomy	O
+,	O
+when	O
+its	O
+incorporation	O
+should	O
+be	O
+maximum	O
+,	O
+failed	O
+to	O
+induce	O
+any	O
+gamma	O
+-	O
+GT	O
+positive	O
+foci	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+hypomethylation	O
+of	O
+DNA	O
+per	O
+se	O
+may	O
+not	O
+be	O
+sufficient	O
+for	O
+initiation	O
+.	O
+
+Perhaps	O
+two	O
+events	O
+might	O
+be	O
+necessary	O
+for	O
+initiation	O
+,	O
+the	O
+first	O
+caused	O
+by	O
+the	O
+carcinogen	O
+and	O
+a	O
+second	O
+involving	O
+hypomethylation	O
+of	O
+DNA	O
+.	O
+
+Antihypertensive	O
+drugs	O
+and	O
+depression	B-Disease
+:	O
+a	O
+reappraisal	O
+.	O
+
+Eighty	O
+-	O
+nine	O
+new	O
+referral	O
+hypertensive	B-Disease
+out	O
+-	O
+patients	O
+and	O
+46	O
+new	O
+referral	O
+non	O
+-	O
+hypertensive	B-Disease
+chronically	O
+physically	O
+ill	O
+out	O
+-	O
+patients	O
+completed	O
+a	O
+mood	O
+rating	O
+scale	O
+at	O
+regular	O
+intervals	O
+for	O
+one	O
+year	O
+.	O
+
+The	O
+results	O
+showed	O
+a	O
+high	O
+prevalence	O
+of	O
+depression	B-Disease
+in	O
+both	O
+groups	O
+of	O
+patients	O
+,	O
+with	O
+no	O
+preponderance	O
+in	O
+the	O
+hypertensive	B-Disease
+group	O
+.	O
+
+Hypertensive	B-Disease
+patients	O
+with	O
+psychiatric	B-Disease
+histories	O
+had	O
+a	O
+higher	O
+prevalence	O
+of	O
+depression	B-Disease
+than	O
+the	O
+comparison	O
+patients	O
+.	O
+
+This	O
+was	O
+accounted	O
+for	O
+by	O
+a	O
+significant	O
+number	O
+of	O
+depressions	B-Disease
+occurring	O
+in	O
+methyl	B-Chemical
+dopa	I-Chemical
+treated	O
+patients	O
+with	O
+psychiatric	B-Disease
+histories	O
+.	O
+
+Chronic	B-Disease
+active	I-Disease
+hepatitis	I-Disease
+associated	O
+with	O
+diclofenac	B-Chemical
+sodium	I-Chemical
+therapy	O
+.	O
+
+Diclofenac	B-Chemical
+sodium	I-Chemical
+(	O
+Voltarol	B-Chemical
+,	O
+Geigy	O
+Pharmaceuticals	O
+)	O
+is	O
+a	O
+non	O
+-	O
+steroidal	O
+anti	O
+-	O
+inflammatory	O
+derivative	O
+of	O
+phenylacetic	B-Chemical
+acid	I-Chemical
+.	O
+
+Although	O
+generally	O
+well	O
+-	O
+tolerated	O
+,	O
+asymptomatic	O
+abnormalities	B-Disease
+of	I-Disease
+liver	I-Disease
+function	I-Disease
+have	O
+been	O
+recorded	O
+and	O
+,	O
+less	O
+commonly	O
+,	O
+severe	O
+hepatitis	B-Disease
+induced	O
+by	O
+diclofenac	B-Chemical
+.	O
+
+The	O
+patient	O
+described	O
+developed	O
+chronic	B-Disease
+active	I-Disease
+hepatitis	I-Disease
+after	O
+six	O
+months	O
+therapy	O
+with	O
+diclofenac	B-Chemical
+sodium	I-Chemical
+which	O
+progressed	O
+despite	O
+the	O
+withdrawal	O
+of	O
+the	O
+drug	O
+,	O
+a	O
+finding	O
+not	O
+previously	O
+reported	O
+.	O
+
+Arterial	O
+hypertension	B-Disease
+as	O
+a	O
+complication	O
+of	O
+prolonged	O
+ketoconazole	B-Chemical
+treatment	O
+.	O
+
+Two	O
+of	O
+14	O
+patients	O
+with	O
+Cushing	B-Disease
+'	I-Disease
+s	I-Disease
+syndrome	I-Disease
+treated	O
+on	O
+a	O
+long	O
+-	O
+term	O
+basis	O
+with	O
+ketoconazole	B-Chemical
+developed	O
+sustained	O
+hypertension	B-Disease
+.	O
+
+In	O
+both	O
+cases	O
+normal	O
+plasma	O
+and	O
+urinary	O
+free	O
+cortisol	B-Chemical
+levels	O
+had	O
+been	O
+achieved	O
+following	O
+ketoconazole	B-Chemical
+therapy	O
+,	O
+yet	O
+continuous	O
+blood	O
+pressure	O
+monitoring	O
+demonstrated	O
+hypertension	B-Disease
+31	O
+(	O
+patient	O
+1	O
+)	O
+and	O
+52	O
+weeks	O
+(	O
+patient	O
+2	O
+)	O
+after	O
+treatment	O
+.	O
+
+In	O
+patient	O
+1	O
+,	O
+plasma	O
+levels	O
+of	O
+deoxycorticosterone	B-Chemical
+and	O
+11	B-Chemical
+-	I-Chemical
+deoxycortisol	I-Chemical
+were	O
+elevated	O
+.	O
+
+In	O
+patient	O
+2	O
+,	O
+in	O
+addition	O
+to	O
+an	O
+increase	O
+in	O
+both	O
+deoxycorticosterone	B-Chemical
+and	O
+11	B-Chemical
+-	I-Chemical
+deoxycortisol	I-Chemical
+levels	O
+,	O
+plasma	O
+aldosterone	B-Chemical
+values	O
+were	O
+raised	O
+,	O
+with	O
+a	O
+concomitant	O
+suppression	O
+of	O
+renin	O
+levels	O
+.	O
+
+Our	O
+findings	O
+show	O
+that	O
+long	O
+-	O
+term	O
+treatment	O
+with	O
+high	O
+doses	O
+of	O
+ketoconazole	B-Chemical
+may	O
+induce	O
+enzyme	O
+blockade	O
+leading	O
+to	O
+mineralocorticoid	O
+-	O
+related	O
+hypertension	B-Disease
+.	O
+
+Effects	O
+of	O
+an	O
+inhibitor	O
+of	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+(	O
+Captopril	B-Chemical
+)	O
+on	O
+pulmonary	B-Disease
+and	I-Disease
+renal	I-Disease
+insufficiency	I-Disease
+due	O
+to	O
+intravascular	B-Disease
+coagulation	I-Disease
+in	O
+the	O
+rat	O
+.	O
+
+Induction	O
+of	O
+intravascular	B-Disease
+coagulation	I-Disease
+and	O
+inhibition	O
+of	O
+fibrinolysis	O
+by	O
+injection	O
+of	O
+thrombin	O
+and	O
+tranexamic	B-Chemical
+acid	I-Chemical
+(	O
+AMCA	B-Chemical
+)	O
+in	O
+the	O
+rat	O
+gives	O
+rise	O
+to	O
+pulmonary	B-Disease
+and	I-Disease
+renal	I-Disease
+insufficiency	I-Disease
+resembling	O
+that	O
+occurring	O
+after	O
+trauma	B-Disease
+or	O
+sepsis	B-Disease
+in	O
+man	O
+.	O
+
+Injection	O
+of	O
+Captopril	B-Chemical
+(	O
+1	O
+mg	O
+/	O
+kg	O
+)	O
+,	O
+an	O
+inhibitor	O
+of	O
+angiotensin	B-Chemical
+converting	O
+enzyme	O
+(	O
+ACE	O
+)	O
+,	O
+reduced	O
+both	O
+pulmonary	B-Disease
+and	I-Disease
+renal	I-Disease
+insufficiency	I-Disease
+in	O
+this	O
+rat	O
+model	O
+.	O
+
+The	O
+lung	O
+weights	O
+were	O
+lower	O
+and	O
+PaO2	O
+was	O
+improved	O
+in	O
+rats	O
+given	O
+this	O
+enzyme	O
+-	O
+blocking	O
+agent	O
+.	O
+
+The	O
+contents	O
+of	O
+albumin	O
+in	O
+the	O
+lungs	O
+were	O
+not	O
+changed	O
+,	O
+indicating	O
+that	O
+Captopril	B-Chemical
+did	O
+not	O
+influence	O
+the	O
+extravasation	O
+of	O
+protein	O
+.	O
+
+Renal	B-Disease
+damage	I-Disease
+as	O
+reflected	O
+by	O
+an	O
+increase	O
+in	O
+serum	O
+urea	B-Chemical
+and	O
+in	O
+kidney	O
+weight	O
+was	O
+prevented	O
+by	O
+Captopril	B-Chemical
+.	O
+
+The	O
+amount	O
+of	O
+fibrin	O
+in	O
+the	O
+kidneys	O
+was	O
+also	O
+considerably	O
+lower	O
+than	O
+in	O
+animals	O
+which	O
+received	O
+thrombin	O
+and	O
+AMCA	B-Chemical
+alone	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+the	O
+effects	O
+of	O
+Captopril	B-Chemical
+on	O
+the	O
+lungs	O
+may	O
+be	O
+attributable	O
+to	O
+a	O
+vasodilatory	O
+effect	O
+due	O
+to	O
+a	O
+reduction	O
+in	O
+the	O
+circulating	O
+level	O
+of	O
+Angiotension	B-Chemical
+II	I-Chemical
+and	O
+an	O
+increase	O
+in	O
+prostacyclin	B-Chemical
+(	O
+secondary	O
+to	O
+an	O
+increase	O
+in	O
+bradykinin	B-Chemical
+)	O
+.	O
+
+Captopril	B-Chemical
+may	O
+,	O
+by	O
+the	O
+same	O
+mechanism	O
+,	O
+reduce	O
+the	O
+increase	O
+in	O
+glomerular	O
+filtration	O
+that	O
+is	O
+known	O
+to	O
+occur	O
+after	O
+an	O
+injection	O
+of	O
+thrombin	O
+,	O
+thereby	O
+diminishing	O
+the	O
+aggregation	O
+of	O
+fibrin	O
+monomers	O
+in	O
+the	O
+glomeruli	O
+,	O
+with	O
+the	O
+result	O
+that	O
+less	O
+fibrin	O
+will	O
+be	O
+deposited	O
+and	O
+thus	O
+less	O
+kidney	B-Disease
+damage	I-Disease
+will	O
+be	O
+produced	O
+.	O
+
+Stroke	B-Disease
+associated	O
+with	O
+cocaine	B-Chemical
+use	O
+.	O
+
+We	O
+describe	O
+eight	O
+patients	O
+in	O
+whom	O
+cocaine	B-Chemical
+use	O
+was	O
+related	O
+to	O
+stroke	B-Disease
+and	O
+review	O
+39	O
+cases	O
+from	O
+the	O
+literature	O
+.	O
+
+Among	O
+these	O
+47	O
+patients	O
+the	O
+mean	O
+(	O
++	O
+/	O
+-	O
+SD	O
+)	O
+age	O
+was	O
+32	O
+.	O
+5	O
++	O
+/	O
+-	O
+12	O
+.	O
+1	O
+years	O
+;	O
+76	O
+%	O
+(	O
+34	O
+/	O
+45	O
+)	O
+were	O
+men	O
+.	O
+
+Stroke	B-Disease
+followed	O
+cocaine	B-Chemical
+use	O
+by	O
+inhalation	O
+,	O
+intranasal	O
+,	O
+intravenous	O
+,	O
+and	O
+intramuscular	O
+routes	O
+.	O
+
+Intracranial	B-Disease
+aneurysms	I-Disease
+or	O
+arteriovenous	B-Disease
+malformations	I-Disease
+were	O
+present	O
+in	O
+17	O
+of	O
+32	O
+patients	O
+studied	O
+angiographically	O
+or	O
+at	O
+autopsy	O
+;	O
+cerebral	B-Disease
+vasculitis	I-Disease
+was	O
+present	O
+in	O
+two	O
+patients	O
+.	O
+
+Cerebral	B-Disease
+infarction	I-Disease
+occurred	O
+in	O
+10	O
+patients	O
+(	O
+22	O
+%	O
+)	O
+,	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+in	O
+22	O
+(	O
+49	O
+%	O
+)	O
+,	O
+and	O
+subarachnoid	B-Disease
+hemorrhage	I-Disease
+in	O
+13	O
+(	O
+29	O
+%	O
+)	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+(	O
+1	O
+)	O
+the	O
+apparent	O
+incidence	O
+of	O
+stroke	B-Disease
+related	O
+to	O
+cocaine	B-Chemical
+use	O
+is	O
+increasing	O
+;	O
+(	O
+2	O
+)	O
+cocaine	B-Chemical
+-	O
+associated	O
+stroke	B-Disease
+occurs	O
+primarily	O
+in	O
+young	O
+adults	O
+;	O
+(	O
+3	O
+)	O
+stroke	B-Disease
+may	O
+follow	O
+any	O
+route	O
+of	O
+cocaine	B-Chemical
+administration	O
+;	O
+(	O
+4	O
+)	O
+stroke	B-Disease
+after	O
+cocaine	B-Chemical
+use	O
+is	O
+frequently	O
+associated	O
+with	O
+intracranial	B-Disease
+aneurysms	I-Disease
+and	O
+arteriovenous	B-Disease
+malformations	I-Disease
+;	O
+and	O
+(	O
+5	O
+)	O
+in	O
+cocaine	B-Chemical
+-	O
+associated	O
+stroke	B-Disease
+,	O
+the	O
+frequency	O
+of	O
+intracranial	B-Disease
+hemorrhage	I-Disease
+exceeds	O
+that	O
+of	O
+cerebral	B-Disease
+infarction	I-Disease
+.	O
+
+A	O
+randomized	O
+comparison	O
+of	O
+labetalol	B-Chemical
+and	O
+nitroprusside	B-Chemical
+for	O
+induced	O
+hypotension	B-Disease
+.	O
+
+In	O
+a	O
+randomized	O
+study	O
+,	O
+labetalol	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+and	O
+nitroprusside	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+were	O
+compared	O
+in	O
+20	O
+patients	O
+(	O
+10	O
+in	O
+each	O
+group	O
+)	O
+scheduled	O
+for	O
+major	O
+orthopedic	O
+procedures	O
+.	O
+
+Each	O
+patient	O
+was	O
+subjected	O
+to	O
+an	O
+identical	O
+anesthetic	O
+protocol	O
+and	O
+similar	O
+drug	O
+-	O
+induced	O
+reductions	B-Disease
+in	I-Disease
+mean	I-Disease
+arterial	I-Disease
+blood	I-Disease
+pressure	I-Disease
+(	O
+BP	O
+)	O
+(	O
+50	O
+to	O
+55	O
+mmHg	O
+)	O
+.	O
+
+Nitroprusside	O
+infusion	O
+was	O
+associated	O
+with	O
+a	O
+significant	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+increase	B-Disease
+in	I-Disease
+heart	I-Disease
+rate	I-Disease
+and	I-Disease
+cardiac	I-Disease
+output	I-Disease
+;	O
+rebound	O
+hypertension	B-Disease
+was	O
+observed	O
+in	O
+three	O
+patients	O
+after	O
+discontinuation	O
+of	O
+nitroprusside	B-Chemical
+.	O
+
+Labetalol	B-Chemical
+administration	O
+was	O
+not	O
+associated	O
+with	O
+any	O
+of	O
+these	O
+findings	O
+.	O
+
+Arterial	O
+PO2	B-Chemical
+decreased	O
+in	O
+both	O
+groups	O
+.	O
+
+It	O
+was	O
+concluded	O
+that	O
+labetalol	B-Chemical
+offers	O
+advantages	O
+over	O
+nitroprusside	B-Chemical
+.	O
+
+Sodium	B-Chemical
+status	O
+influences	O
+chronic	O
+amphotericin	B-Chemical
+B	I-Chemical
+nephrotoxicity	B-Disease
+in	O
+rats	O
+.	O
+
+The	O
+nephrotoxic	B-Disease
+potential	O
+of	O
+amphotericin	B-Chemical
+B	I-Chemical
+(	O
+5	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+intraperitoneally	O
+for	O
+3	O
+weeks	O
+)	O
+has	O
+been	O
+investigated	O
+in	O
+salt	O
+-	O
+depleted	O
+,	O
+normal	O
+-	O
+salt	O
+,	O
+and	O
+salt	O
+-	O
+loaded	O
+rats	O
+.	O
+
+In	O
+salt	O
+-	O
+depleted	O
+rats	O
+,	O
+amphotericin	B-Chemical
+B	I-Chemical
+decreased	O
+creatinine	B-Chemical
+clearance	O
+linearly	O
+with	O
+time	O
+,	O
+with	O
+an	O
+85	O
+%	O
+reduction	O
+by	O
+week	O
+3	O
+.	O
+
+In	O
+contrast	O
+,	O
+in	O
+normal	O
+-	O
+salt	O
+rats	O
+creatinine	B-Chemical
+clearance	O
+was	O
+decreased	O
+but	O
+to	O
+a	O
+lesser	O
+extent	O
+at	O
+week	O
+2	O
+and	O
+3	O
+,	O
+and	O
+in	O
+salt	O
+-	O
+loaded	O
+rats	O
+creatinine	B-Chemical
+clearance	O
+did	O
+not	O
+change	O
+for	O
+2	O
+weeks	O
+and	O
+was	O
+decreased	O
+by	O
+43	O
+%	O
+at	O
+week	O
+3	O
+.	O
+
+All	O
+rats	O
+in	O
+the	O
+sodium	B-Chemical
+-	O
+depleted	O
+group	O
+had	O
+histopathological	O
+evidence	O
+of	O
+patchy	O
+tubular	O
+cytoplasmic	O
+degeneration	O
+in	O
+tubules	O
+that	O
+was	O
+not	O
+observed	O
+in	O
+any	O
+normal	O
+-	O
+salt	O
+or	O
+salt	O
+-	O
+loaded	O
+rat	O
+.	O
+
+Concentrations	O
+of	O
+amphotericin	B-Chemical
+B	I-Chemical
+in	O
+plasma	O
+were	O
+not	O
+significantly	O
+different	O
+among	O
+the	O
+three	O
+groups	O
+at	O
+any	O
+time	O
+during	O
+the	O
+study	O
+.	O
+
+However	O
+,	O
+at	O
+the	O
+end	O
+of	O
+3	O
+weeks	O
+,	O
+amphotericin	B-Chemical
+B	I-Chemical
+levels	O
+in	O
+the	O
+kidneys	O
+and	O
+liver	O
+were	O
+significantly	O
+higher	O
+in	O
+salt	O
+-	O
+depleted	O
+and	O
+normal	O
+-	O
+salt	O
+rats	O
+than	O
+those	O
+in	O
+salt	O
+-	O
+loaded	O
+rats	O
+,	O
+with	O
+plasma	O
+/	O
+kidney	O
+ratios	O
+of	O
+21	O
+,	O
+14	O
+,	O
+and	O
+8	O
+in	O
+salt	O
+-	O
+depleted	O
+,	O
+normal	O
+-	O
+salt	O
+,	O
+and	O
+salt	O
+-	O
+loaded	O
+rats	O
+,	O
+respectively	O
+.	O
+
+In	O
+conclusion	O
+,	O
+reductions	O
+in	O
+creatinine	B-Chemical
+clearance	O
+and	O
+renal	O
+amphotericin	B-Chemical
+B	I-Chemical
+accumulation	O
+after	O
+chronic	O
+amphotericin	B-Chemical
+B	I-Chemical
+administration	O
+were	O
+enhanced	O
+by	O
+salt	O
+depletion	O
+and	O
+attenuated	O
+by	O
+sodium	B-Chemical
+loading	O
+in	O
+rats	O
+.	O
+
+Flestolol	B-Chemical
+:	O
+an	O
+ultra	O
+-	O
+short	O
+-	O
+acting	O
+beta	O
+-	O
+adrenergic	O
+blocking	O
+agent	O
+.	O
+
+Flestolol	B-Chemical
+(	O
+ACC	B-Chemical
+-	I-Chemical
+9089	I-Chemical
+)	O
+is	O
+a	O
+nonselective	O
+,	O
+competitive	O
+,	O
+ultra	O
+-	O
+short	O
+-	O
+acting	O
+beta	O
+-	O
+adrenergic	O
+blocking	O
+agent	O
+,	O
+without	O
+any	O
+intrinsic	O
+sympathomimetic	O
+activity	O
+.	O
+
+Flestolol	B-Chemical
+is	O
+metabolized	O
+by	O
+plasma	O
+esterases	O
+and	O
+has	O
+an	O
+elimination	O
+half	O
+-	O
+life	O
+of	O
+approximately	O
+6	O
+.	O
+5	O
+minutes	O
+.	O
+
+This	O
+agent	O
+was	O
+well	O
+tolerated	O
+in	O
+healthy	O
+volunteers	O
+at	O
+doses	O
+up	O
+to	O
+100	O
+micrograms	O
+/	O
+kg	O
+/	O
+min	O
+.	O
+
+In	O
+long	O
+-	O
+term	O
+infusion	O
+studies	O
+,	O
+flestolol	B-Chemical
+was	O
+well	O
+tolerated	O
+at	O
+the	O
+effective	O
+beta	O
+-	O
+blocking	O
+dose	O
+(	O
+5	O
+micrograms	O
+/	O
+kg	O
+/	O
+min	O
+)	O
+for	O
+up	O
+to	O
+seven	O
+days	O
+.	O
+
+Flestolol	B-Chemical
+blood	O
+concentrations	O
+increased	O
+linearly	O
+with	O
+increasing	O
+dose	O
+and	O
+good	O
+correlation	O
+exists	O
+between	O
+blood	O
+concentrations	O
+of	O
+flestolol	B-Chemical
+and	O
+beta	O
+-	O
+adrenergic	O
+blockade	O
+.	O
+
+Flestolol	B-Chemical
+produced	O
+a	O
+dose	O
+-	O
+dependent	O
+attenuation	O
+of	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+tachycardia	B-Disease
+.	O
+
+Electrophysiologic	O
+and	O
+hemodynamic	O
+effects	O
+of	O
+flestolol	B-Chemical
+are	O
+similar	O
+to	O
+those	O
+of	O
+other	O
+beta	O
+blockers	O
+.	O
+
+In	O
+contrast	O
+with	O
+other	O
+beta	O
+blockers	O
+,	O
+flestolol	B-Chemical
+-	O
+induced	O
+effects	O
+reverse	O
+rapidly	O
+(	O
+within	O
+30	O
+minutes	O
+)	O
+following	O
+discontinuation	O
+because	O
+of	O
+its	O
+short	O
+half	O
+-	O
+life	O
+.	O
+
+Flestolol	B-Chemical
+effectively	O
+reduced	O
+heart	O
+rate	O
+in	O
+patients	O
+with	O
+supraventricular	B-Disease
+tachyarrhythmia	I-Disease
+.	O
+
+In	O
+patients	O
+with	O
+unstable	B-Disease
+angina	I-Disease
+,	O
+flestolol	B-Chemical
+infusion	O
+was	O
+found	O
+to	O
+be	O
+safe	O
+and	O
+effective	O
+in	O
+controlling	O
+chest	B-Disease
+pain	I-Disease
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+flestolol	B-Chemical
+is	O
+a	O
+potent	O
+,	O
+well	O
+-	O
+tolerated	O
+,	O
+ultra	O
+-	O
+short	O
+-	O
+acting	O
+beta	O
+-	O
+adrenergic	O
+blocking	O
+agent	O
+.	O
+
+Use	O
+of	O
+flestolol	B-Chemical
+in	O
+the	O
+critical	O
+care	O
+setting	O
+is	O
+currently	O
+undergoing	O
+investigation	O
+.	O
+
+Immunohistochemical	O
+,	O
+electron	O
+microscopic	O
+and	O
+morphometric	O
+studies	O
+of	O
+estrogen	B-Chemical
+-	O
+induced	O
+rat	O
+prolactinomas	B-Disease
+after	O
+bromocriptine	B-Chemical
+treatment	O
+.	O
+
+To	O
+clarify	O
+the	O
+effects	O
+of	O
+bromocriptine	B-Chemical
+on	O
+prolactinoma	B-Disease
+cells	O
+in	O
+vivo	O
+,	O
+immunohistochemical	O
+,	O
+ultrastructural	O
+and	O
+morphometrical	O
+analyses	O
+were	O
+applied	O
+to	O
+estrogen	B-Chemical
+-	O
+induced	O
+rat	O
+prolactinoma	B-Disease
+cells	O
+1	O
+h	O
+and	O
+6	O
+h	O
+after	O
+injection	O
+of	O
+bromocriptine	B-Chemical
+(	O
+3	O
+mg	O
+/	O
+kg	O
+of	O
+body	O
+weight	O
+)	O
+.	O
+
+One	O
+h	O
+after	O
+treatment	O
+,	O
+serum	O
+prolactin	O
+levels	O
+decreased	O
+markedly	O
+.	O
+
+Electron	O
+microscopy	O
+disclosed	O
+many	O
+secretory	O
+granules	O
+,	O
+slightly	O
+distorted	O
+rough	O
+endoplasmic	O
+reticulum	O
+,	O
+and	O
+partially	O
+dilated	O
+Golgi	O
+cisternae	O
+in	O
+the	O
+prolactinoma	B-Disease
+cells	O
+.	O
+
+Morphometric	O
+analysis	O
+revealed	O
+that	O
+the	O
+volume	O
+density	O
+of	O
+secretory	O
+granules	O
+increased	O
+,	O
+while	O
+the	O
+volume	O
+density	O
+of	O
+cytoplasmic	O
+microtubules	O
+decreased	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+lowered	O
+serum	O
+prolactin	O
+levels	O
+in	O
+the	O
+early	O
+phase	O
+of	O
+bromocriptine	B-Chemical
+treatment	O
+may	O
+result	O
+from	O
+an	O
+impaired	O
+secretion	O
+of	O
+prolactin	O
+due	O
+to	O
+decreasing	O
+numbers	O
+of	O
+cytoplasmic	O
+microtubules	O
+.	O
+
+At	O
+6	O
+h	O
+after	O
+injection	O
+,	O
+serum	O
+prolactin	O
+levels	O
+were	O
+still	O
+considerably	O
+lower	O
+than	O
+in	O
+controls	O
+.	O
+
+The	O
+prolactinoma	B-Disease
+cells	O
+at	O
+this	O
+time	O
+were	O
+well	O
+granulated	O
+,	O
+with	O
+vesiculated	O
+rough	O
+endoplasmic	O
+reticulum	O
+and	O
+markedly	O
+dilated	O
+Golgi	O
+cisternae	O
+.	O
+
+Electron	O
+microscopical	O
+immunohistochemistry	O
+revealed	O
+positive	O
+reaction	O
+products	O
+noted	O
+on	O
+the	O
+secretory	O
+granules	O
+,	O
+Golgi	O
+cisternae	O
+,	O
+and	O
+endoplasmic	O
+reticulum	O
+of	O
+the	O
+untreated	O
+rat	O
+prolactinoma	B-Disease
+cells	O
+.	O
+
+However	O
+,	O
+only	O
+secretory	O
+granules	O
+showed	O
+the	O
+positive	O
+reaction	O
+products	O
+for	O
+prolactin	O
+6	O
+h	O
+after	O
+bromocriptine	B-Chemical
+treatment	O
+of	O
+the	O
+adenoma	B-Disease
+cells	O
+.	O
+
+An	O
+increase	O
+in	O
+the	O
+volume	O
+density	O
+of	O
+secretory	O
+granules	O
+and	O
+a	O
+decrease	O
+in	O
+the	O
+volume	O
+densities	O
+of	O
+rough	O
+endoplasmic	O
+reticulum	O
+and	O
+microtubules	O
+was	O
+determined	O
+by	O
+morphometric	O
+analysis	O
+,	O
+suggesting	O
+that	O
+bromocriptine	B-Chemical
+inhibits	O
+protein	O
+synthesis	O
+as	O
+well	O
+as	O
+bringing	O
+about	O
+a	O
+disturbance	O
+of	O
+the	O
+prolactin	O
+secretion	O
+.	O
+
+Sulfasalazine	B-Chemical
+-	O
+induced	O
+lupus	B-Disease
+erythematosus	I-Disease
+.	O
+
+Pneumonitis	B-Disease
+,	O
+bilateral	O
+pleural	B-Disease
+effusions	I-Disease
+,	O
+echocardiographic	O
+evidence	O
+of	O
+cardiac	B-Disease
+tamponade	I-Disease
+,	O
+and	O
+positive	O
+autoantibodies	O
+developed	O
+in	O
+a	O
+43	O
+-	O
+year	O
+-	O
+old	O
+man	O
+,	O
+who	O
+was	O
+receiving	O
+long	O
+-	O
+term	O
+sulfasalazine	B-Chemical
+therapy	O
+for	O
+chronic	O
+ulcerative	B-Disease
+colitis	I-Disease
+.	O
+
+After	O
+cessation	O
+of	O
+the	O
+sulfasalazine	B-Chemical
+and	O
+completion	O
+of	O
+a	O
+six	O
+-	O
+week	O
+course	O
+of	O
+corticosteroids	O
+,	O
+these	O
+problems	O
+resolved	O
+over	O
+a	O
+period	O
+of	O
+four	O
+to	O
+six	O
+months	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+the	O
+patient	O
+had	O
+sulfasalazine	B-Chemical
+-	O
+induced	O
+lupus	B-Disease
+,	O
+which	O
+manifested	O
+with	O
+serositis	B-Disease
+and	O
+pulmonary	O
+parenchymal	O
+involvement	O
+in	O
+the	O
+absence	O
+of	O
+joint	O
+symptoms	O
+.	O
+
+Physicians	O
+who	O
+use	O
+sulfasalazine	B-Chemical
+to	O
+treat	O
+patients	O
+with	O
+inflammatory	B-Disease
+bowel	I-Disease
+disease	I-Disease
+should	O
+be	O
+aware	O
+of	O
+the	O
+signs	O
+of	O
+sulfasalazine	B-Chemical
+-	O
+induced	O
+lupus	B-Disease
+syndrome	I-Disease
+.	O
+
+Chronic	O
+carbamazepine	B-Chemical
+treatment	O
+in	O
+the	O
+rat	O
+:	O
+efficacy	O
+,	O
+toxicity	B-Disease
+,	O
+and	O
+effect	O
+on	O
+plasma	O
+and	O
+tissue	O
+folate	B-Chemical
+concentrations	O
+.	O
+
+Folate	B-Chemical
+depletion	O
+has	O
+often	O
+been	O
+a	O
+problem	O
+in	O
+chronic	O
+antiepileptic	O
+drug	O
+(	O
+AED	O
+)	O
+therapy	O
+.	O
+
+Carbamazepine	B-Chemical
+(	O
+CBZ	B-Chemical
+)	O
+,	O
+a	O
+commonly	O
+used	O
+AED	O
+,	O
+has	O
+been	O
+implicated	O
+in	O
+some	O
+clinical	O
+studies	O
+.	O
+
+A	O
+rat	O
+model	O
+was	O
+developed	O
+to	O
+examine	O
+the	O
+effects	O
+of	O
+chronic	O
+CBZ	B-Chemical
+treatment	O
+on	O
+folate	B-Chemical
+concentrations	O
+in	O
+the	O
+rat	O
+.	O
+
+In	O
+the	O
+course	O
+of	O
+developing	O
+this	O
+model	O
+,	O
+a	O
+common	O
+vehicle	O
+,	O
+propylene	B-Chemical
+glycol	I-Chemical
+,	O
+by	O
+itself	O
+in	O
+high	O
+doses	O
+,	O
+was	O
+found	O
+to	O
+exhibit	O
+protective	O
+properties	O
+against	O
+induced	O
+seizures	B-Disease
+and	O
+inhibited	O
+weight	B-Disease
+gain	I-Disease
+.	O
+
+Seizures	B-Disease
+induced	O
+by	O
+hexafluorodiethyl	B-Chemical
+ether	I-Chemical
+(	O
+HFDE	B-Chemical
+)	O
+were	O
+also	O
+found	O
+to	O
+be	O
+a	O
+more	O
+sensitive	O
+measure	O
+of	O
+protection	O
+by	O
+CBZ	B-Chemical
+than	O
+seizures	B-Disease
+induced	O
+by	O
+maximal	O
+electroshock	O
+(	O
+MES	O
+)	O
+.	O
+
+Oral	O
+administration	O
+of	O
+CBZ	B-Chemical
+as	O
+an	O
+aqueous	O
+suspension	O
+every	O
+8	O
+h	O
+at	O
+a	O
+dose	O
+of	O
+250	O
+mg	O
+/	O
+kg	O
+was	O
+continuously	O
+protective	O
+against	O
+HFDE	B-Chemical
+-	O
+induced	O
+seizures	B-Disease
+and	O
+was	O
+minimally	O
+toxic	O
+as	O
+measured	O
+by	O
+weight	B-Disease
+gain	I-Disease
+over	O
+8	O
+weeks	O
+of	O
+treatment	O
+.	O
+
+The	O
+CBZ	B-Chemical
+levels	O
+measured	O
+in	O
+plasma	O
+and	O
+brain	O
+of	O
+these	O
+animals	O
+,	O
+however	O
+,	O
+were	O
+below	O
+those	O
+normally	O
+considered	O
+protective	O
+.	O
+
+This	O
+treatment	O
+with	O
+CBZ	B-Chemical
+had	O
+no	O
+apparent	O
+adverse	O
+effect	O
+on	O
+folate	B-Chemical
+concentrations	O
+in	O
+the	O
+rat	O
+,	O
+and	O
+,	O
+indeed	O
+,	O
+the	O
+folate	B-Chemical
+concentration	O
+increased	O
+in	O
+liver	O
+after	O
+6	O
+weeks	O
+of	O
+treatment	O
+and	O
+in	O
+plasma	O
+at	O
+8	O
+weeks	O
+of	O
+treatment	O
+.	O
+
+Dipyridamole	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+ischemia	I-Disease
+.	O
+
+Angina	B-Disease
+and	O
+ischemic	O
+electrocardiographic	O
+changes	O
+occurred	O
+after	O
+administration	O
+of	O
+oral	O
+dipyridamole	B-Chemical
+in	O
+four	O
+patients	O
+awaiting	O
+urgent	O
+myocardial	O
+revascularization	O
+procedures	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+has	O
+not	O
+previously	O
+been	O
+reported	O
+as	O
+a	O
+side	O
+effect	O
+of	O
+preoperative	O
+dipyridamole	B-Chemical
+therapy	O
+,	O
+although	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+ischemia	I-Disease
+has	O
+been	O
+demonstrated	O
+to	O
+occur	O
+in	O
+animals	O
+and	O
+humans	O
+with	O
+coronary	B-Disease
+artery	I-Disease
+disease	I-Disease
+.	O
+
+Epicardial	O
+coronary	O
+collateral	O
+vessels	O
+were	O
+demonstrated	O
+in	O
+all	O
+four	O
+patients	O
+;	O
+a	O
+coronary	O
+"	O
+steal	O
+"	O
+phenomenon	O
+may	O
+be	O
+the	O
+mechanism	O
+of	O
+the	O
+dipyridamole	B-Chemical
+-	O
+induced	O
+ischemia	B-Disease
+observed	O
+.	O
+
+Inhibition	O
+of	O
+sympathoadrenal	O
+activity	O
+by	O
+atrial	O
+natriuretic	O
+factor	O
+in	O
+dogs	O
+.	O
+
+In	O
+six	O
+conscious	O
+,	O
+trained	O
+dogs	O
+,	O
+maintained	O
+on	O
+a	O
+normal	O
+sodium	B-Chemical
+intake	O
+of	O
+2	O
+to	O
+4	O
+mEq	O
+/	O
+kg	O
+/	O
+day	O
+,	O
+sympathetic	O
+activity	O
+was	O
+assessed	O
+as	O
+the	O
+release	O
+rate	O
+of	O
+norepinephrine	B-Chemical
+and	O
+epinephrine	B-Chemical
+during	O
+15	O
+-	O
+minute	O
+i	O
+.	O
+v	O
+.	O
+infusions	O
+of	O
+human	O
+alpha	O
+-	O
+atrial	O
+natriuretic	O
+factor	O
+.	O
+
+Mean	O
+arterial	O
+pressure	O
+(	O
+as	O
+a	O
+percentage	O
+of	O
+control	O
++	O
+/	O
+-	O
+SEM	O
+)	O
+during	O
+randomized	O
+infusions	O
+of	O
+0	O
+.	O
+03	O
+,	O
+0	O
+.	O
+1	O
+,	O
+0	O
+.	O
+3	O
+,	O
+or	O
+1	O
+.	O
+0	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+was	O
+99	O
++	O
+/	O
+-	O
+1	O
+,	O
+95	O
++	O
+/	O
+-	O
+1	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+,	O
+93	O
++	O
+/	O
+-	O
+1	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+01	O
+)	O
+,	O
+or	O
+79	O
++	O
+/	O
+-	O
+6	O
+%	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+,	O
+respectively	O
+,	O
+but	O
+no	O
+tachycardia	B-Disease
+and	O
+no	O
+augmentation	O
+of	O
+the	O
+norepinephrine	B-Chemical
+release	O
+rate	O
+(	O
+up	O
+to	O
+0	O
+.	O
+3	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+)	O
+were	O
+observed	O
+,	O
+which	O
+is	O
+in	O
+contrast	O
+to	O
+comparable	O
+hypotension	B-Disease
+induced	O
+by	O
+hydralazine	B-Chemical
+or	O
+nitroglycerin	B-Chemical
+.	O
+
+The	O
+release	O
+rate	O
+of	O
+epinephrine	B-Chemical
+(	O
+control	O
+,	O
+6	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+6	O
+ng	O
+/	O
+kg	O
+/	O
+min	O
+)	O
+declined	O
+immediately	O
+during	O
+infusions	O
+of	O
+atrial	O
+natriuretic	O
+factor	O
+to	O
+a	O
+minimum	O
+of	O
+49	O
++	O
+/	O
+-	O
+5	O
+%	O
+of	O
+control	O
+(	O
+p	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+during	O
+0	O
+.	O
+1	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+and	O
+to	O
+63	O
++	O
+/	O
+-	O
+5	O
+%	O
+(	O
+0	O
+.	O
+1	O
+greater	O
+than	O
+p	O
+greater	O
+than	O
+0	O
+.	O
+05	O
+)	O
+or	O
+95	O
++	O
+/	O
+-	O
+13	O
+%	O
+(	O
+not	O
+significant	O
+)	O
+during	O
+0	O
+.	O
+3	O
+or	O
+1	O
+.	O
+0	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+.	O
+
+Steady	O
+state	O
+arterial	O
+plasma	O
+concentrations	O
+of	O
+atrial	O
+natriuretic	O
+factor	O
+were	O
+39	O
++	O
+/	O
+-	O
+10	O
+pg	O
+/	O
+ml	O
+(	O
+n	O
+=	O
+6	O
+)	O
+during	O
+infusions	O
+of	O
+saline	O
+and	O
+284	O
++	O
+/	O
+-	O
+24	O
+pg	O
+/	O
+ml	O
+(	O
+n	O
+=	O
+6	O
+)	O
+and	O
+1520	O
++	O
+/	O
+-	O
+300	O
+pg	O
+/	O
+ml	O
+(	O
+n	O
+=	O
+9	O
+)	O
+during	O
+0	O
+.	O
+03	O
+and	O
+0	O
+.	O
+1	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+infusions	O
+of	O
+the	O
+factor	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Inhibition	O
+of	O
+immunoreactive	O
+corticotropin	O
+-	O
+releasing	O
+factor	O
+secretion	O
+into	O
+the	O
+hypophysial	O
+-	O
+portal	O
+circulation	O
+by	O
+delayed	O
+glucocorticoid	O
+feedback	O
+.	O
+
+Nitroprusside	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+evokes	O
+ACTH	O
+secretion	O
+which	O
+is	O
+primarily	O
+mediated	O
+by	O
+enhanced	O
+secretion	O
+of	O
+immunoreactive	O
+corticotropin	O
+-	O
+releasing	O
+factor	O
+(	O
+irCRF	O
+)	O
+into	O
+the	O
+hypophysial	O
+-	O
+portal	O
+circulation	O
+.	O
+
+Portal	O
+plasma	O
+concentrations	O
+of	O
+neither	O
+arginine	B-Chemical
+vasopressin	I-Chemical
+nor	O
+oxytocin	B-Chemical
+are	O
+significantly	O
+altered	O
+in	O
+this	O
+paradigm	O
+.	O
+
+Application	O
+of	O
+a	O
+delayed	O
+feedback	O
+signal	O
+,	O
+in	O
+the	O
+form	O
+of	O
+a	O
+2	O
+-	O
+h	O
+systemic	O
+corticosterone	B-Chemical
+infusion	O
+in	O
+urethane	B-Chemical
+-	O
+anesthetized	O
+rats	O
+with	O
+pharmacological	O
+blockade	O
+of	O
+glucocorticoid	O
+synthesis	O
+,	O
+is	O
+without	O
+effect	O
+on	O
+the	O
+resting	O
+secretion	O
+of	O
+arginine	B-Chemical
+vasopressin	I-Chemical
+and	O
+oxytocin	B-Chemical
+at	O
+any	O
+corticosterone	B-Chemical
+feedback	O
+dose	O
+tested	O
+.	O
+
+Resting	O
+irCRF	O
+levels	O
+are	O
+suppressed	O
+only	O
+at	O
+the	O
+highest	O
+corticosterone	B-Chemical
+infusion	O
+rate	O
+,	O
+which	O
+resulted	O
+in	O
+systemic	O
+corticosterone	B-Chemical
+levels	O
+of	O
+40	O
+micrograms	O
+/	O
+dl	O
+.	O
+
+Suppression	O
+of	O
+irCRF	O
+secretion	O
+in	O
+response	O
+to	O
+nitroprusside	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+is	O
+observed	O
+and	O
+occurs	O
+at	O
+a	O
+plasma	O
+corticosterone	B-Chemical
+level	O
+between	O
+8	O
+-	O
+12	O
+micrograms	O
+/	O
+dl	O
+.	O
+
+These	O
+studies	O
+provide	O
+further	O
+evidence	O
+for	O
+a	O
+strong	O
+central	O
+component	O
+of	O
+the	O
+delayed	O
+feedback	O
+process	O
+which	O
+is	O
+mediated	O
+by	O
+modulation	O
+of	O
+irCRF	O
+release	O
+.	O
+
+Noradrenergic	O
+involvement	O
+in	O
+catalepsy	B-Disease
+induced	O
+by	O
+delta	B-Chemical
+9	I-Chemical
+-	I-Chemical
+tetrahydrocannabinol	I-Chemical
+.	O
+
+In	O
+order	O
+to	O
+elucidate	O
+the	O
+role	O
+of	O
+the	O
+catecholaminergic	O
+system	O
+in	O
+the	O
+cataleptogenic	O
+effect	O
+of	O
+delta	B-Chemical
+9	I-Chemical
+-	I-Chemical
+tetrahydrocannabinol	I-Chemical
+(	O
+THC	B-Chemical
+)	O
+,	O
+the	O
+effect	O
+of	O
+pretreatment	O
+with	O
+6	B-Chemical
+-	I-Chemical
+hydroxydopamine	I-Chemical
+(	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+)	O
+or	O
+with	O
+desipramine	B-Chemical
+and	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+and	O
+lesions	O
+of	O
+the	O
+locus	O
+coeruleus	O
+were	O
+investigated	O
+in	O
+rats	O
+.	O
+
+The	O
+cataleptogenic	O
+effect	O
+of	O
+THC	B-Chemical
+was	O
+significantly	O
+reduced	O
+in	O
+rats	O
+treated	O
+with	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+and	O
+in	O
+rats	O
+with	O
+lesions	O
+of	O
+the	O
+locus	O
+coeruleus	O
+but	O
+not	O
+in	O
+rats	O
+treated	O
+with	O
+desipramine	B-Chemical
+and	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+,	O
+as	O
+compared	O
+with	O
+control	O
+rats	O
+.	O
+
+On	O
+the	O
+contrary	O
+,	O
+the	O
+cataleptogenic	O
+effect	O
+of	O
+haloperidol	B-Chemical
+was	O
+significantly	O
+reduced	O
+in	O
+rats	O
+treated	O
+with	O
+desipramine	B-Chemical
+and	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+but	O
+not	O
+in	O
+rats	O
+treated	O
+with	O
+6	B-Chemical
+-	I-Chemical
+OHDA	I-Chemical
+or	O
+in	O
+rats	O
+with	O
+lesions	O
+of	O
+the	O
+locus	O
+coeruleus	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+noradrenergic	O
+neurons	O
+have	O
+an	O
+important	O
+role	O
+in	O
+the	O
+manifestation	O
+of	O
+catalepsy	B-Disease
+induced	O
+by	O
+THC	B-Chemical
+,	O
+whereas	O
+dopaminergic	O
+neurons	O
+are	O
+important	O
+in	O
+catalepsy	B-Disease
+induced	O
+by	O
+haloperidol	B-Chemical
+.	O
+
+Reversibility	O
+of	O
+captopril	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+insufficiency	I-Disease
+after	O
+prolonged	O
+use	O
+in	O
+an	O
+unusual	O
+case	O
+of	O
+renovascular	B-Disease
+hypertension	I-Disease
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+severe	O
+hypertension	B-Disease
+with	O
+an	O
+occluded	O
+renal	O
+artery	O
+to	O
+a	O
+solitary	O
+kidney	O
+,	O
+who	O
+developed	O
+sudden	B-Disease
+deterioration	I-Disease
+of	I-Disease
+renal	I-Disease
+function	I-Disease
+following	O
+treatment	O
+with	O
+captopril	B-Chemical
+.	O
+
+His	O
+renal	O
+function	O
+remained	O
+impaired	O
+but	O
+stable	O
+during	O
+2	O
+years	O
+'	O
+treatment	O
+with	O
+captopril	B-Chemical
+but	O
+returned	O
+to	O
+pre	O
+-	O
+treatment	O
+levels	O
+soon	O
+after	O
+cessation	O
+of	O
+the	O
+drug	O
+.	O
+
+This	O
+indicates	O
+reversibility	O
+in	O
+captopril	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+failure	I-Disease
+even	O
+after	O
+its	O
+prolonged	O
+use	O
+and	O
+suggests	O
+that	O
+no	O
+organic	O
+damage	O
+occurs	O
+to	O
+glomerular	O
+arterioles	O
+following	O
+chronic	O
+ACE	O
+inhibition	O
+.	O
+
+HMG	O
+CoA	O
+reductase	O
+inhibitors	O
+.	O
+
+Current	O
+clinical	O
+experience	O
+.	O
+
+Lovastatin	B-Chemical
+and	O
+simvastatin	B-Chemical
+are	O
+the	O
+2	O
+best	O
+-	O
+known	O
+members	O
+of	O
+the	O
+class	O
+of	O
+hypolipidaemic	O
+agents	O
+known	O
+as	O
+HMG	O
+CoA	O
+reductase	O
+inhibitors	O
+.	O
+
+Clinical	O
+experience	O
+with	O
+lovastatin	B-Chemical
+includes	O
+over	O
+5000	O
+patients	O
+,	O
+700	O
+of	O
+whom	O
+have	O
+been	O
+treated	O
+for	O
+2	O
+years	O
+or	O
+more	O
+,	O
+and	O
+experience	O
+with	O
+simvastatin	B-Chemical
+includes	O
+over	O
+3500	O
+patients	O
+,	O
+of	O
+whom	O
+350	O
+have	O
+been	O
+treated	O
+for	O
+18	O
+months	O
+or	O
+more	O
+.	O
+
+Lovastatin	B-Chemical
+has	O
+been	O
+marketed	O
+in	O
+the	O
+United	O
+States	O
+for	O
+over	O
+6	O
+months	O
+.	O
+
+Both	O
+agents	O
+show	O
+substantial	O
+clinical	O
+efficacy	O
+,	O
+with	O
+reductions	O
+in	O
+total	O
+cholesterol	B-Chemical
+of	O
+over	O
+30	O
+%	O
+and	O
+in	O
+LDL	O
+-	O
+cholesterol	B-Chemical
+of	O
+40	O
+%	O
+in	O
+clinical	O
+studies	O
+.	O
+
+Modest	O
+increases	O
+in	O
+HDL	O
+-	O
+cholesterol	B-Chemical
+levels	O
+of	O
+about	O
+10	O
+%	O
+are	O
+also	O
+reported	O
+.	O
+
+Clinical	O
+tolerability	O
+of	O
+both	O
+agents	O
+has	O
+been	O
+good	O
+,	O
+with	O
+fewer	O
+than	O
+3	O
+%	O
+of	O
+patients	O
+withdrawn	O
+from	O
+treatment	O
+because	O
+of	O
+clinical	O
+adverse	O
+experiences	O
+.	O
+
+Ophthalmological	O
+examinations	O
+in	O
+over	O
+1100	O
+patients	O
+treated	O
+with	O
+one	O
+or	O
+the	O
+other	O
+agent	O
+have	O
+revealed	O
+no	O
+evidence	O
+of	O
+significant	O
+short	O
+term	O
+(	O
+up	O
+to	O
+2	O
+years	O
+)	O
+cataractogenic	O
+potential	O
+.	O
+
+One	O
+to	O
+2	O
+%	O
+of	O
+patients	O
+have	O
+elevations	O
+of	O
+serum	O
+transaminases	O
+to	O
+greater	O
+than	O
+3	O
+times	O
+the	O
+upper	O
+limit	O
+of	O
+normal	O
+.	O
+
+These	O
+episodes	O
+are	O
+asymptomatic	O
+and	O
+reversible	O
+when	O
+therapy	O
+is	O
+discontinued	O
+.	O
+
+Minor	O
+elevations	O
+of	O
+creatine	B-Chemical
+kinase	O
+levels	O
+are	O
+reported	O
+in	O
+about	O
+5	O
+%	O
+of	O
+patients	O
+.	O
+
+Myopathy	B-Disease
+,	O
+associated	O
+in	O
+some	O
+cases	O
+with	O
+myoglobinuria	B-Disease
+,	O
+and	O
+in	O
+2	O
+cases	O
+with	O
+transient	O
+renal	B-Disease
+failure	I-Disease
+,	O
+has	O
+been	O
+rarely	O
+reported	O
+with	O
+lovastatin	B-Chemical
+,	O
+especially	O
+in	O
+patients	O
+concomitantly	O
+treated	O
+with	O
+cyclosporin	B-Chemical
+,	O
+gemfibrozil	B-Chemical
+or	O
+niacin	B-Chemical
+.	O
+
+Lovastatin	B-Chemical
+and	O
+simvastatin	B-Chemical
+are	O
+both	O
+effective	O
+and	O
+well	O
+-	O
+tolerated	O
+agents	O
+for	O
+lowering	O
+elevated	O
+levels	O
+of	O
+serum	O
+cholesterol	B-Chemical
+.	O
+
+As	O
+wider	O
+use	O
+confirms	O
+their	O
+safety	O
+profile	O
+,	O
+they	O
+will	O
+gain	O
+increasing	O
+importance	O
+in	O
+the	O
+therapeutic	O
+approach	O
+to	O
+hypercholesterolaemia	B-Disease
+and	O
+its	O
+consequences	O
+.	O
+
+Hepatic	O
+reactions	O
+associated	O
+with	O
+ketoconazole	B-Chemical
+in	O
+the	O
+United	O
+Kingdom	O
+.	O
+
+Ketoconazole	B-Chemical
+was	O
+introduced	O
+in	O
+the	O
+United	O
+Kingdom	O
+in	O
+1981	O
+.	O
+
+By	O
+November	O
+1984	O
+the	O
+Committee	O
+on	O
+Safety	O
+of	O
+Medicines	O
+had	O
+received	O
+82	O
+reports	O
+of	O
+possible	O
+hepatotoxicity	B-Disease
+associated	O
+with	O
+the	O
+drug	O
+,	O
+including	O
+five	O
+deaths	B-Disease
+.	O
+
+An	O
+analysis	O
+of	O
+the	O
+75	O
+cases	O
+that	O
+had	O
+been	O
+adequately	O
+followed	O
+up	O
+suggested	O
+that	O
+16	O
+,	O
+including	O
+three	O
+deaths	B-Disease
+,	O
+were	O
+probably	O
+related	O
+to	O
+treatment	O
+with	O
+the	O
+drug	O
+.	O
+
+Of	O
+the	O
+remainder	O
+,	O
+48	O
+were	O
+possibly	O
+related	O
+to	O
+treatment	O
+,	O
+five	O
+were	O
+unlikely	O
+to	O
+be	O
+so	O
+,	O
+and	O
+six	O
+were	O
+unclassifiable	O
+.	O
+
+The	O
+mean	O
+age	O
+of	O
+patients	O
+in	O
+the	O
+16	O
+probable	O
+cases	O
+was	O
+57	O
+.	O
+9	O
+,	O
+with	O
+hepatotoxicity	B-Disease
+being	O
+more	O
+common	O
+in	O
+women	O
+.	O
+
+The	O
+average	O
+duration	O
+of	O
+treatment	O
+before	O
+the	O
+onset	O
+of	O
+jaundice	B-Disease
+was	O
+61	O
+days	O
+.	O
+
+None	O
+of	O
+these	O
+well	O
+validated	O
+cases	O
+occurred	O
+within	O
+the	O
+first	O
+10	O
+days	O
+after	O
+treatment	O
+.	O
+
+The	O
+results	O
+of	O
+serum	O
+liver	O
+function	O
+tests	O
+suggested	O
+hepatocellular	B-Disease
+injury	I-Disease
+in	O
+10	O
+(	O
+63	O
+%	O
+)	O
+;	O
+the	O
+rest	O
+showed	O
+a	O
+mixed	O
+pattern	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+results	O
+of	O
+histological	O
+examination	O
+of	O
+the	O
+liver	O
+often	O
+showed	O
+evidence	O
+of	O
+cholestasis	B-Disease
+.	O
+
+The	O
+characteristics	O
+of	O
+the	O
+48	O
+patients	O
+in	O
+the	O
+possible	O
+cases	O
+were	O
+similar	O
+.	O
+
+Allergic	O
+manifestations	O
+such	O
+as	O
+rash	B-Disease
+and	O
+eosinophilia	B-Disease
+were	O
+rare	O
+.	O
+
+Hepatitis	B-Disease
+was	O
+usually	O
+reversible	O
+when	O
+treatment	O
+was	O
+stopped	O
+,	O
+with	O
+the	O
+results	O
+of	O
+liver	O
+function	O
+tests	O
+returning	O
+to	O
+normal	O
+after	O
+an	O
+average	O
+of	O
+3	O
+.	O
+1	O
+months	O
+.	O
+
+In	O
+two	O
+of	O
+the	O
+three	O
+deaths	B-Disease
+probably	O
+associated	O
+with	O
+ketoconazole	B-Chemical
+treatment	O
+the	O
+drug	O
+had	O
+been	O
+continued	O
+after	O
+the	O
+onset	O
+of	O
+jaundice	B-Disease
+and	O
+other	O
+symptoms	O
+of	O
+hepatitis	B-Disease
+.	O
+
+Clinical	O
+and	O
+biochemical	O
+monitoring	O
+at	O
+regular	O
+intervals	O
+for	O
+evidence	O
+of	O
+hepatitis	B-Disease
+is	O
+advised	O
+during	O
+long	O
+term	O
+treatment	O
+with	O
+ketoconazole	B-Chemical
+to	O
+prevent	O
+possible	O
+serious	O
+hepatic	B-Disease
+injury	I-Disease
+.	O
+
+Glyburide	B-Chemical
+-	O
+induced	O
+hepatitis	B-Disease
+.	O
+
+Drug	O
+-	O
+induced	O
+hepatotoxicity	B-Disease
+,	O
+although	O
+common	O
+,	O
+has	O
+been	O
+reported	O
+only	O
+infrequently	O
+with	O
+sulfonylureas	B-Chemical
+.	O
+
+For	O
+glyburide	B-Chemical
+,	O
+a	O
+second	O
+-	O
+generation	O
+sulfonylurea	B-Chemical
+,	O
+only	O
+two	O
+brief	O
+reports	O
+of	O
+hepatotoxicity	B-Disease
+exist	O
+.	O
+
+Two	O
+patients	O
+with	O
+type	B-Disease
+II	I-Disease
+diabetes	I-Disease
+mellitus	I-Disease
+developed	O
+an	O
+acute	B-Disease
+hepatitis	I-Disease
+-	I-Disease
+like	I-Disease
+syndrome	I-Disease
+soon	O
+after	O
+initiation	O
+of	O
+glyburide	B-Chemical
+therapy	O
+.	O
+
+There	O
+was	O
+no	O
+serologic	O
+evidence	O
+of	O
+viral	B-Disease
+infection	I-Disease
+,	O
+and	O
+a	O
+liver	O
+biopsy	O
+sample	O
+showed	O
+a	O
+histologic	O
+pattern	O
+consistent	O
+with	O
+drug	B-Disease
+-	I-Disease
+induced	I-Disease
+hepatitis	I-Disease
+.	O
+
+Both	O
+patients	O
+recovered	O
+quickly	O
+after	O
+stopping	O
+glyburide	B-Chemical
+therapy	O
+and	O
+have	O
+remained	O
+well	O
+for	O
+a	O
+follow	O
+-	O
+up	O
+period	O
+of	O
+1	O
+year	O
+.	O
+
+Glyburide	B-Chemical
+can	O
+produce	O
+an	O
+acute	B-Disease
+hepatitis	I-Disease
+-	I-Disease
+like	I-Disease
+illness	I-Disease
+in	O
+some	O
+persons	O
+.	O
+
+Intracranial	O
+pressure	O
+increases	O
+during	O
+alfentanil	B-Chemical
+-	O
+induced	O
+rigidity	B-Disease
+.	O
+
+Intracranial	O
+pressure	O
+(	O
+ICP	O
+)	O
+was	O
+measured	O
+during	O
+alfentanil	B-Chemical
+-	O
+induced	O
+rigidity	B-Disease
+in	O
+rats	O
+.	O
+
+Ten	O
+rats	O
+had	O
+arterial	O
+,	O
+central	O
+venous	O
+(	O
+CVP	O
+)	O
+,	O
+and	O
+subdural	O
+cannulae	O
+inserted	O
+under	O
+halothane	B-Chemical
+anesthesia	O
+.	O
+
+The	O
+animals	O
+were	O
+mechanically	O
+ventilated	O
+to	O
+achieve	O
+normocarbia	O
+(	O
+PCO2	O
+=	O
+42	O
++	O
+/	O
+-	O
+1	O
+mmHg	O
+,	O
+mean	O
++	O
+/	O
+-	O
+SE	O
+)	O
+.	O
+
+Following	O
+instrumentation	O
+,	O
+halothane	B-Chemical
+was	O
+discontinued	O
+and	O
+alfentanil	B-Chemical
+(	O
+125	O
+mu	O
+/	O
+kg	O
+)	O
+administered	O
+iv	O
+during	O
+emergence	O
+from	O
+halothane	B-Chemical
+anesthesia	O
+.	O
+
+In	O
+the	O
+five	O
+rats	O
+that	O
+developed	O
+somatic	B-Disease
+rigidity	I-Disease
+,	O
+ICP	O
+and	O
+CVP	O
+increased	O
+significantly	O
+above	O
+baseline	O
+(	O
+delta	O
+ICP	O
+7	O
+.	O
+5	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+mmHg	O
+,	O
+delta	O
+CVP	O
+5	O
+.	O
+9	O
++	O
+/	O
+-	O
+1	O
+.	O
+3	O
+mmHg	O
+)	O
+.	O
+
+These	O
+variables	O
+returned	O
+to	O
+baseline	O
+when	O
+rigidity	B-Disease
+was	O
+abolished	O
+with	O
+metocurine	B-Chemical
+.	O
+
+In	O
+five	O
+rats	O
+that	O
+did	O
+not	O
+become	O
+rigid	O
+,	O
+ICP	O
+and	O
+CVP	O
+did	O
+not	O
+change	O
+following	O
+alfentanil	B-Chemical
+.	O
+
+These	O
+observations	O
+suggest	O
+that	O
+rigidity	B-Disease
+should	O
+be	O
+prevented	O
+when	O
+alfentanil	B-Chemical
+,	O
+and	O
+,	O
+presumably	O
+,	O
+other	O
+opiates	O
+,	O
+are	O
+used	O
+in	O
+the	O
+anesthetic	O
+management	O
+of	O
+patients	O
+with	O
+ICP	O
+problems	O
+.	O
+
+Verapamil	B-Chemical
+withdrawal	O
+as	O
+a	O
+possible	O
+cause	O
+of	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+a	O
+hypertensive	B-Disease
+woman	O
+with	O
+a	O
+normal	O
+coronary	O
+angiogram	O
+.	O
+
+Verapamil	B-Chemical
+is	O
+an	O
+effective	O
+and	O
+relatively	O
+-	O
+safe	O
+antihypertensive	O
+drug	O
+.	O
+
+Serious	O
+adverse	O
+effects	O
+are	O
+uncommon	O
+and	O
+mainly	O
+have	O
+been	O
+related	O
+to	O
+the	O
+depression	B-Disease
+of	O
+cardiac	O
+contractility	O
+and	O
+conduction	O
+,	O
+especially	O
+when	O
+the	O
+drug	O
+is	O
+combined	O
+with	O
+beta	O
+-	O
+blocking	O
+agents	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+in	O
+which	O
+myocardial	B-Disease
+infarction	I-Disease
+coincided	O
+with	O
+the	O
+introduction	O
+of	O
+captopril	B-Chemical
+and	O
+the	O
+withdrawal	O
+of	O
+verapamil	B-Chemical
+in	O
+a	O
+previously	O
+asymptomatic	O
+woman	O
+with	O
+severe	O
+hypertension	B-Disease
+.	O
+
+Possible	O
+mechanisms	O
+that	O
+involve	O
+a	O
+verapamil	B-Chemical
+-	O
+related	O
+increase	O
+in	O
+platelet	O
+and	O
+/	O
+or	O
+vascular	O
+alpha	O
+2	O
+-	O
+adrenoreceptor	O
+affinity	O
+for	O
+catecholamines	B-Chemical
+are	O
+discussed	O
+.	O
+
+Haemolytic	B-Disease
+-	I-Disease
+uraemic	I-Disease
+syndrome	I-Disease
+after	O
+treatment	O
+with	O
+metronidazole	B-Chemical
+.	O
+
+This	O
+paper	O
+describes	O
+the	O
+clinical	O
+features	O
+of	O
+six	O
+children	O
+who	O
+developed	O
+the	O
+haemolytic	B-Disease
+-	I-Disease
+uraemic	I-Disease
+syndrome	I-Disease
+after	O
+treatment	O
+with	O
+metronidazole	B-Chemical
+.	O
+
+These	O
+children	O
+were	O
+older	O
+and	O
+were	O
+more	O
+likely	O
+to	O
+have	O
+undergone	O
+recent	O
+bowel	O
+surgery	O
+than	O
+are	O
+other	O
+children	O
+with	O
+this	O
+condition	O
+.	O
+
+While	O
+the	O
+involvement	O
+of	O
+metronidazole	B-Chemical
+in	O
+the	O
+aetiology	O
+of	O
+the	O
+haemolytic	B-Disease
+-	I-Disease
+uraemic	I-Disease
+syndrome	I-Disease
+is	O
+not	O
+established	O
+firmly	O
+,	O
+the	O
+action	O
+of	O
+this	O
+drug	O
+in	O
+sensitizing	O
+tissues	O
+to	O
+oxidation	O
+injury	O
+and	O
+the	O
+reported	O
+evidence	O
+of	O
+oxidation	O
+changes	O
+in	O
+the	O
+haemolytic	B-Disease
+-	I-Disease
+uraemic	I-Disease
+syndrome	I-Disease
+suggest	O
+a	O
+possible	O
+link	O
+between	O
+metronidazole	B-Chemical
+treatment	O
+and	O
+some	O
+cases	O
+of	O
+the	O
+haemolytic	B-Disease
+-	I-Disease
+uraemic	I-Disease
+syndrome	I-Disease
+.	O
+
+Adverse	O
+cardiac	O
+effects	O
+during	O
+induction	O
+chemotherapy	O
+treatment	O
+with	O
+cis	B-Chemical
+-	I-Chemical
+platin	I-Chemical
+and	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+.	O
+
+Survival	O
+for	O
+patients	O
+with	O
+advanced	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+carcinoma	I-Disease
+and	O
+esophageal	B-Disease
+carcinoma	I-Disease
+is	O
+poor	O
+with	O
+radiotherapy	O
+and	O
+/	O
+or	O
+surgery	O
+.	O
+
+Obviously	O
+,	O
+there	O
+is	O
+a	O
+need	O
+for	O
+effective	O
+chemotherapy	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+cis	B-Chemical
+-	I-Chemical
+platin	I-Chemical
+(	O
+80	O
+-	O
+120	O
+mg	O
+/	O
+m2BSA	O
+)	O
+and	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+(	O
+1000	O
+mg	O
+/	O
+m2BSA	O
+daily	O
+as	O
+a	O
+continuous	O
+infusion	O
+during	O
+5	O
+days	O
+)	O
+were	O
+given	O
+to	O
+76	O
+patients	O
+before	O
+radiotherapy	O
+and	O
+surgery	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+clarify	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+adverse	O
+cardiac	O
+effects	O
+to	O
+this	O
+treatment	O
+.	O
+
+Before	O
+treatment	O
+all	O
+patients	O
+had	O
+a	O
+cardiac	O
+evaluation	O
+and	O
+during	O
+treatment	O
+serial	O
+ECG	O
+recordings	O
+were	O
+performed	O
+.	O
+
+In	O
+the	O
+pre	O
+-	O
+treatment	O
+evaluation	O
+,	O
+signs	O
+of	O
+cardiovascular	B-Disease
+disease	I-Disease
+were	O
+found	O
+in	O
+33	O
+patients	O
+(	O
+43	O
+%	O
+)	O
+.	O
+
+During	O
+treatment	O
+,	O
+adverse	O
+cardiac	O
+effects	O
+were	O
+observed	O
+in	O
+14	O
+patients	O
+(	O
+18	O
+%	O
+)	O
+.	O
+
+The	O
+mean	O
+age	O
+of	O
+these	O
+patients	O
+was	O
+the	O
+same	O
+as	O
+for	O
+the	O
+entire	O
+group	O
+,	O
+64	O
+years	O
+.	O
+
+The	O
+incidence	O
+of	O
+cardiotoxicity	B-Disease
+was	O
+not	O
+higher	O
+in	O
+patients	O
+with	O
+signs	O
+of	O
+cardiovascular	B-Disease
+disease	I-Disease
+than	O
+in	O
+those	O
+without	O
+in	O
+the	O
+pre	O
+-	O
+treatment	O
+evaluation	O
+.	O
+
+The	O
+most	O
+common	O
+signs	O
+of	O
+cardiotoxicity	B-Disease
+were	O
+chest	B-Disease
+pain	I-Disease
+,	O
+ST	O
+-	O
+T	O
+wave	O
+changes	O
+and	O
+atrial	B-Disease
+fibrillation	I-Disease
+.	O
+
+This	O
+was	O
+followed	O
+by	O
+ventricular	B-Disease
+fibrillation	I-Disease
+in	O
+one	O
+patient	O
+and	O
+sudden	B-Disease
+death	I-Disease
+in	O
+another	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+patients	O
+on	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+treatment	O
+should	O
+be	O
+under	O
+close	O
+supervision	O
+and	O
+that	O
+the	O
+treatment	O
+should	O
+be	O
+discontinued	O
+if	O
+chest	B-Disease
+pain	I-Disease
+or	O
+tachyarrhythmia	B-Disease
+is	O
+observed	O
+.	O
+
+Death	B-Disease
+from	O
+chemotherapy	O
+in	O
+gestational	B-Disease
+trophoblastic	I-Disease
+disease	I-Disease
+.	O
+
+Multiple	O
+cytotoxic	O
+drug	O
+administration	O
+is	O
+the	O
+generally	O
+accepted	O
+treatment	O
+of	O
+patients	O
+with	O
+a	O
+high	O
+-	O
+risk	O
+stage	O
+of	O
+choriocarcinoma	B-Disease
+.	O
+
+Based	O
+on	O
+this	O
+principle	O
+a	O
+27	O
+-	O
+year	O
+old	O
+woman	O
+,	O
+classified	O
+as	O
+being	O
+in	O
+the	O
+high	O
+-	O
+risk	O
+group	O
+(	O
+Goldstein	O
+and	O
+Berkowitz	O
+score	O
+:	O
+11	O
+)	O
+,	O
+was	O
+treated	O
+with	O
+multiple	O
+cytotoxic	O
+drugs	O
+.	O
+
+The	O
+multiple	O
+drug	O
+schema	O
+consisted	O
+of	O
+:	O
+Etoposide	B-Chemical
+16	O
+.	O
+213	O
+,	O
+Methotrexate	B-Chemical
+,	O
+Cyclophosphamide	B-Chemical
+,	O
+Actomycin	B-Chemical
+-	I-Chemical
+D	I-Chemical
+,	O
+and	O
+Cisplatin	B-Chemical
+.	O
+
+On	O
+the	O
+first	O
+day	O
+of	O
+the	O
+schedule	O
+,	O
+moderate	O
+high	O
+doses	O
+of	O
+Methotrexate	B-Chemical
+,	O
+Etoposide	B-Chemical
+and	O
+Cyclophosphamide	B-Chemical
+were	O
+administered	O
+.	O
+
+Within	O
+8	O
+hours	O
+after	O
+initiation	O
+of	O
+therapy	O
+the	O
+patient	O
+died	O
+with	O
+a	O
+clinical	O
+picture	O
+resembling	O
+massive	O
+pulmonary	B-Disease
+obstruction	I-Disease
+due	O
+to	O
+choriocarcinomic	O
+tissue	O
+plugs	O
+,	O
+probably	O
+originating	O
+from	O
+the	O
+uterus	O
+.	O
+
+Formation	O
+of	O
+these	O
+plugs	O
+was	O
+probably	O
+due	O
+to	O
+extensive	O
+tumor	B-Disease
+necrosis	B-Disease
+at	O
+the	O
+level	O
+of	O
+the	O
+walls	O
+of	O
+the	O
+major	O
+uterine	O
+veins	O
+,	O
+which	O
+resulted	O
+in	O
+an	O
+open	O
+exchange	O
+of	O
+tumor	B-Disease
+plugs	O
+to	O
+the	O
+vascular	O
+spaces	O
+;	O
+decrease	O
+in	O
+tumor	B-Disease
+tissue	O
+coherence	O
+secondary	O
+to	O
+chemotherapy	O
+may	O
+have	O
+further	O
+contributed	O
+to	O
+the	O
+formation	O
+of	O
+tumor	B-Disease
+emboli	O
+.	O
+
+In	O
+view	O
+of	O
+the	O
+close	O
+time	O
+association	O
+between	O
+the	O
+start	O
+of	O
+chemotherapy	O
+and	O
+the	O
+acute	O
+onset	O
+of	O
+massive	O
+embolism	B-Disease
+other	O
+explanations	O
+,	O
+such	O
+as	O
+spontaneous	O
+necrosis	B-Disease
+,	O
+must	O
+be	O
+considered	O
+less	O
+likely	O
+.	O
+
+Patients	O
+with	O
+large	O
+pelvic	B-Disease
+tumor	I-Disease
+loads	O
+are	O
+,	O
+according	O
+to	O
+existing	O
+classifications	O
+,	O
+at	O
+high	O
+risk	O
+to	O
+die	O
+and	O
+to	O
+develop	O
+drug	O
+resistance	O
+.	O
+
+Notwithstanding	O
+these	O
+facts	O
+our	O
+findings	O
+suggest	O
+that	O
+these	O
+patients	O
+might	O
+benefit	O
+from	O
+relatively	O
+mild	O
+initial	O
+treatment	O
+,	O
+especially	O
+true	O
+for	O
+patients	O
+not	O
+previously	O
+exposed	O
+to	O
+this	O
+drug	O
+.	O
+
+Close	O
+observation	O
+of	O
+the	O
+response	O
+status	O
+both	O
+clinically	O
+and	O
+with	O
+beta	O
+-	O
+hCG	O
+values	O
+may	O
+indicate	O
+whether	O
+and	O
+when	O
+more	O
+agressive	O
+combination	O
+chemotherapy	O
+should	O
+be	O
+started	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Pulmonary	O
+shunt	O
+and	O
+cardiovascular	O
+responses	O
+to	O
+CPAP	O
+during	O
+nitroprusside	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+The	O
+effects	O
+of	O
+continuous	O
+positive	O
+airway	O
+pressure	O
+(	O
+CPAP	O
+)	O
+on	O
+cardiovascular	O
+dynamics	O
+and	O
+pulmonary	O
+shunt	O
+(	O
+QS	O
+/	O
+QT	O
+)	O
+were	O
+investigated	O
+in	O
+12	O
+dogs	O
+before	O
+and	O
+during	O
+sodium	B-Chemical
+nitroprusside	I-Chemical
+infusion	O
+that	O
+decreased	O
+mean	O
+arterial	O
+blood	O
+pressure	O
+40	O
+-	O
+50	O
+per	O
+cent	O
+.	O
+
+Before	O
+nitroprusside	B-Chemical
+infusion	O
+,	O
+5	O
+cm	O
+H2O	B-Chemical
+CPAP	O
+significantly	O
+,	O
+P	O
+less	O
+than	O
+.	O
+05	O
+,	O
+decreased	O
+arterial	O
+blood	O
+pressure	O
+,	O
+but	O
+did	O
+not	O
+significantly	O
+alter	O
+heart	O
+rate	O
+,	O
+cardiac	O
+output	O
+,	O
+systemic	O
+vascular	O
+resistance	O
+,	O
+or	O
+QS	O
+/	O
+QT	O
+.	O
+
+Ten	O
+cm	O
+H2O	B-Chemical
+CPAP	O
+before	O
+nitroprusside	B-Chemical
+infusion	O
+produced	O
+a	O
+further	O
+decrease	B-Disease
+in	I-Disease
+arterial	I-Disease
+blood	I-Disease
+pressure	I-Disease
+and	O
+significantly	O
+increased	O
+heart	O
+rate	O
+and	O
+decreased	B-Disease
+cardiac	I-Disease
+output	I-Disease
+and	O
+QS	O
+/	O
+QT	O
+.	O
+
+Nitroprusside	B-Chemical
+caused	O
+significant	O
+decreases	B-Disease
+in	I-Disease
+arterial	I-Disease
+blood	I-Disease
+pressure	I-Disease
+and	O
+systemic	O
+vascular	O
+resistance	O
+and	O
+increases	O
+in	O
+heart	O
+rate	O
+,	O
+but	O
+did	O
+not	O
+change	O
+cardiac	O
+output	O
+or	O
+QS	O
+/	O
+QT	O
+.	O
+
+Five	O
+cm	O
+H2O	B-Chemical
+CPAP	O
+during	O
+nitroprusside	B-Chemical
+did	O
+not	O
+further	O
+alter	O
+any	O
+of	O
+the	O
+above	O
+-	O
+mentioned	O
+variables	O
+.	O
+
+However	O
+,	O
+10	O
+cm	O
+H2O	B-Chemical
+CPAP	O
+decreased	O
+arterial	O
+blood	O
+pressure	O
+,	O
+cardiac	O
+output	O
+,	O
+and	O
+QS	O
+/	O
+QT	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+nitroprusside	B-Chemical
+infusion	O
+rates	O
+that	O
+decrease	O
+mean	O
+arterial	O
+blood	O
+pressure	O
+by	O
+40	O
+-	O
+50	O
+per	O
+cent	O
+do	O
+not	O
+change	O
+cardiac	O
+output	O
+or	O
+QS	O
+/	O
+QT	O
+.	O
+
+During	O
+nitroprusside	B-Chemical
+infusion	O
+low	O
+levels	O
+of	O
+CPAP	O
+do	O
+not	O
+markedly	O
+alter	O
+cardiovascular	O
+dynamics	O
+,	O
+but	O
+high	O
+levels	O
+of	O
+CPAP	O
+(	O
+10	O
+cm	O
+H2O	B-Chemical
+)	O
+,	O
+while	O
+decreasing	O
+QS	O
+/	O
+QT	O
+,	O
+produce	O
+marked	O
+decreases	B-Disease
+in	I-Disease
+arterial	I-Disease
+blood	I-Disease
+pressure	I-Disease
+and	I-Disease
+cardiac	I-Disease
+output	I-Disease
+.	O
+
+Systolic	O
+pressure	O
+variation	O
+is	O
+greater	O
+during	O
+hemorrhage	B-Disease
+than	O
+during	O
+sodium	B-Chemical
+nitroprusside	I-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+in	O
+ventilated	O
+dogs	O
+.	O
+
+The	O
+systolic	O
+pressure	O
+variation	O
+(	O
+SPV	O
+)	O
+,	O
+which	O
+is	O
+the	O
+difference	O
+between	O
+the	O
+maximal	O
+and	O
+minimal	O
+values	O
+of	O
+the	O
+systolic	O
+blood	O
+pressure	O
+(	O
+SBP	O
+)	O
+after	O
+one	O
+positive	O
+-	O
+pressure	O
+breath	O
+,	O
+was	O
+studied	O
+in	O
+ventilated	O
+dogs	O
+subjected	O
+to	O
+hypotension	B-Disease
+.	O
+
+Mean	O
+arterial	O
+pressure	O
+was	O
+decreased	O
+to	O
+50	O
+mm	O
+Hg	O
+for	O
+30	O
+minutes	O
+either	O
+by	O
+hemorrhage	B-Disease
+(	O
+HEM	B-Disease
+,	O
+n	O
+=	O
+7	O
+)	O
+or	O
+by	O
+continuous	O
+infusion	O
+of	O
+sodium	B-Chemical
+nitroprusside	I-Chemical
+(	O
+SNP	B-Chemical
+,	O
+n	O
+=	O
+7	O
+)	O
+.	O
+
+During	O
+HEM	B-Disease
+-	O
+induced	O
+hypotension	B-Disease
+the	O
+cardiac	O
+output	O
+was	O
+significantly	O
+lower	O
+and	O
+systemic	O
+vascular	O
+resistance	O
+higher	O
+compared	O
+with	O
+that	O
+in	O
+the	O
+SNP	B-Chemical
+group	O
+.	O
+
+The	O
+systemic	O
+,	O
+central	O
+venous	O
+,	O
+pulmonary	O
+capillary	O
+wedge	O
+pressures	O
+,	O
+and	O
+heart	O
+rates	O
+,	O
+were	O
+similar	O
+in	O
+the	O
+two	O
+groups	O
+.	O
+
+Analysis	O
+of	O
+the	O
+respiratory	O
+changes	O
+in	O
+the	O
+arterial	O
+pressure	O
+waveform	O
+enabled	O
+differentiation	O
+between	O
+the	O
+two	O
+groups	O
+.	O
+
+The	O
+SPV	O
+during	O
+hypotension	B-Disease
+was	O
+15	O
+.	O
+7	O
++	O
+/	O
+-	O
+6	O
+.	O
+7	O
+mm	O
+Hg	O
+in	O
+the	O
+HEM	B-Disease
+group	O
+,	O
+compared	O
+with	O
+9	O
+.	O
+1	O
++	O
+/	O
+-	O
+2	O
+.	O
+0	O
+mm	O
+Hg	O
+in	O
+the	O
+SNP	B-Chemical
+group	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+The	O
+delta	O
+down	O
+,	O
+which	O
+is	O
+the	O
+measure	O
+of	O
+decrease	O
+of	O
+SBP	O
+after	O
+a	O
+mechanical	O
+breath	O
+,	O
+was	O
+20	O
+.	O
+3	O
++	O
+/	O
+-	O
+8	O
+.	O
+4	O
+and	O
+10	O
+.	O
+1	O
++	O
+/	O
+-	O
+3	O
+.	O
+8	O
+mm	O
+Hg	O
+in	O
+the	O
+HEM	B-Disease
+and	O
+SNP	B-Chemical
+groups	O
+,	O
+respectively	O
+,	O
+during	O
+hypotension	B-Disease
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+02	O
+)	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+increases	O
+in	O
+the	O
+SPV	O
+and	O
+the	O
+delta	O
+down	O
+are	O
+characteristic	O
+of	O
+a	O
+hypotensive	B-Disease
+state	O
+due	O
+to	O
+a	O
+predominant	O
+decrease	O
+in	O
+preload	O
+.	O
+
+They	O
+are	O
+thus	O
+more	O
+important	O
+during	O
+absolute	O
+hypovolemia	B-Disease
+than	O
+during	O
+deliberate	O
+hypotension	B-Disease
+.	O
+
+Ventricular	B-Disease
+tachyarrhythmias	I-Disease
+during	O
+cesarean	O
+section	O
+after	O
+ritodrine	B-Chemical
+therapy	O
+:	O
+interaction	O
+with	O
+anesthetics	O
+.	O
+
+This	O
+case	O
+illustrates	O
+that	O
+patients	O
+receiving	O
+ritodrine	B-Chemical
+for	O
+preterm	B-Disease
+labor	I-Disease
+may	O
+risk	O
+interactions	O
+between	O
+the	O
+residual	O
+betamimetic	O
+effects	O
+of	O
+ritodrine	B-Chemical
+and	O
+the	O
+effects	O
+of	O
+anesthetics	O
+during	O
+cesarean	O
+section	O
+.	O
+
+Such	O
+interactions	O
+may	O
+result	O
+in	O
+serious	O
+cardiovascular	B-Disease
+complications	I-Disease
+even	O
+after	O
+cessation	O
+of	O
+an	O
+infusion	O
+of	O
+ritodrine	B-Chemical
+.	O
+
+Preoperative	O
+assessment	O
+should	O
+focus	O
+on	O
+cardiovascular	O
+status	O
+and	O
+serum	O
+potassium	B-Chemical
+level	O
+.	O
+
+Delaying	O
+induction	O
+of	O
+anesthesia	O
+should	O
+be	O
+considered	O
+whenever	O
+possible	O
+.	O
+
+Careful	O
+fluid	O
+administration	O
+and	O
+cautious	O
+use	O
+of	O
+titrated	O
+doses	O
+of	O
+ephedrine	B-Chemical
+are	O
+advised	O
+.	O
+
+After	O
+delivery	O
+of	O
+the	O
+infant	O
+,	O
+there	O
+should	O
+be	O
+no	O
+contraindication	O
+to	O
+the	O
+use	O
+of	O
+an	O
+alpha	O
+-	O
+adrenergic	O
+vasopressor	O
+such	O
+as	O
+phenylephrine	B-Chemical
+to	O
+treat	O
+hypotensive	B-Disease
+patients	O
+with	O
+tachycardia	B-Disease
+.	O
+
+Verapamil	B-Chemical
+-	O
+induced	O
+carbamazepine	B-Chemical
+neurotoxicity	B-Disease
+.	O
+
+A	O
+report	O
+of	O
+two	O
+cases	O
+.	O
+
+Two	O
+patients	O
+with	O
+signs	O
+of	O
+carbamazepine	B-Chemical
+neurotoxicity	B-Disease
+after	O
+combined	O
+treatment	O
+with	O
+verapamil	B-Chemical
+showed	O
+complete	O
+recovery	O
+after	O
+discontinuation	O
+of	O
+the	O
+calcium	B-Chemical
+entry	O
+blocker	O
+.	O
+
+Use	O
+of	O
+verapamil	B-Chemical
+in	O
+combination	O
+with	O
+carbamazepine	B-Chemical
+should	O
+either	O
+be	O
+avoided	O
+or	O
+prescribed	O
+only	O
+with	O
+appropriate	O
+adjustment	O
+of	O
+the	O
+carbamazepine	B-Chemical
+dose	O
+(	O
+usually	O
+reduction	O
+of	O
+the	O
+carbamazepine	B-Chemical
+dose	O
+by	O
+one	O
+half	O
+)	O
+.	O
+
+Paracetamol	B-Chemical
+-	O
+associated	O
+coma	B-Disease
+,	O
+metabolic	B-Disease
+acidosis	I-Disease
+,	O
+renal	B-Disease
+and	I-Disease
+hepatic	I-Disease
+failure	I-Disease
+.	O
+
+A	O
+case	O
+of	O
+metabolic	B-Disease
+acidosis	I-Disease
+,	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+and	I-Disease
+hepatic	I-Disease
+failure	I-Disease
+following	O
+paracetamol	B-Chemical
+ingestion	O
+is	O
+presented	O
+.	O
+
+The	O
+diagnostic	O
+difficulty	O
+at	O
+presentation	O
+is	O
+highlighted	O
+.	O
+
+Continuous	O
+arteriovenous	O
+haemofiltration	O
+proved	O
+a	O
+valuable	O
+means	O
+of	O
+maintaining	O
+fluid	O
+and	O
+electrolyte	O
+balance	O
+.	O
+
+The	O
+patient	O
+recovered	O
+.	O
+
+Sexual	B-Disease
+dysfunction	I-Disease
+among	O
+patients	O
+with	O
+arthritis	B-Disease
+.	O
+
+The	O
+relationship	O
+of	O
+arthritis	B-Disease
+and	O
+sexual	B-Disease
+dysfunction	I-Disease
+was	O
+investigated	O
+among	O
+169	O
+patients	O
+with	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+,	O
+osteoarthritis	B-Disease
+and	O
+spondyloarthropathy	B-Disease
+,	O
+130	O
+of	O
+whom	O
+were	O
+pair	O
+-	O
+matched	O
+to	O
+controls	O
+.	O
+
+Assessments	O
+of	O
+marital	O
+happiness	O
+and	O
+depressed	B-Disease
+mood	I-Disease
+were	O
+also	O
+made	O
+using	O
+the	O
+CES	O
+-	O
+D	O
+and	O
+the	O
+Azrin	O
+Marital	O
+Happiness	O
+Scale	O
+(	O
+AMHS	O
+)	O
+.	O
+
+Sexual	B-Disease
+dysfunctions	I-Disease
+were	O
+found	O
+to	O
+be	O
+common	O
+among	O
+patients	O
+and	O
+controls	O
+,	O
+the	O
+majority	O
+in	O
+both	O
+groups	O
+reporting	O
+one	O
+or	O
+more	O
+dysfunctions	O
+.	O
+
+Impotence	B-Disease
+was	O
+more	O
+common	O
+among	O
+male	O
+patients	O
+than	O
+controls	O
+and	O
+was	O
+found	O
+to	O
+be	O
+associated	O
+with	O
+co	O
+-	O
+morbidity	O
+and	O
+the	O
+taking	O
+of	O
+methotrexate	B-Chemical
+.	O
+
+Depressed	B-Disease
+mood	I-Disease
+was	O
+more	O
+common	O
+among	O
+patients	O
+and	O
+was	O
+associated	O
+with	O
+certain	O
+sexual	O
+difficulties	O
+,	O
+but	O
+not	O
+with	O
+impotence	B-Disease
+.	O
+
+Marital	O
+unhappiness	O
+,	O
+as	O
+indicated	O
+by	O
+AMHS	O
+scores	O
+,	O
+was	O
+not	O
+associated	O
+with	O
+arthritis	B-Disease
+but	O
+was	O
+associated	O
+with	O
+sexual	B-Disease
+dysfunction	I-Disease
+,	O
+sexual	O
+dissatisfaction	O
+and	O
+being	O
+female	O
+.	O
+
+Does	O
+paracetamol	B-Chemical
+cause	O
+urothelial	B-Disease
+cancer	I-Disease
+or	O
+renal	B-Disease
+papillary	I-Disease
+necrosis	I-Disease
+?	O
+
+The	O
+risk	O
+of	O
+developing	O
+renal	B-Disease
+papillary	I-Disease
+necrosis	I-Disease
+or	O
+cancer	B-Disease
+of	I-Disease
+the	I-Disease
+renal	I-Disease
+pelvis	I-Disease
+,	I-Disease
+ureter	I-Disease
+or	I-Disease
+bladder	I-Disease
+associated	O
+with	O
+consumption	O
+of	O
+either	O
+phenacetin	B-Chemical
+or	O
+paracetamol	B-Chemical
+was	O
+calculated	O
+from	O
+data	O
+acquired	O
+by	O
+questionnaire	O
+from	O
+381	O
+cases	O
+and	O
+808	O
+controls	O
+.	O
+
+The	O
+risk	O
+of	O
+renal	B-Disease
+papillary	I-Disease
+necrosis	I-Disease
+was	O
+increased	O
+nearly	O
+20	O
+-	O
+fold	O
+by	O
+consumption	O
+of	O
+phenacetin	B-Chemical
+,	O
+which	O
+also	O
+increased	O
+the	O
+risk	O
+for	O
+cancer	B-Disease
+of	I-Disease
+the	I-Disease
+renal	I-Disease
+pelvis	I-Disease
+and	I-Disease
+bladder	I-Disease
+but	O
+not	O
+for	O
+ureteric	B-Disease
+cancer	I-Disease
+.	O
+
+By	O
+contrast	O
+,	O
+we	O
+were	O
+unable	O
+to	O
+substantiate	O
+an	O
+increased	O
+risk	O
+from	O
+paracetamol	B-Chemical
+consumption	O
+for	O
+renal	B-Disease
+papillary	I-Disease
+necrosis	I-Disease
+or	O
+any	O
+of	O
+these	O
+cancers	B-Disease
+although	O
+there	O
+was	O
+a	O
+suggestion	O
+of	O
+an	O
+association	O
+with	O
+cancer	B-Disease
+of	I-Disease
+the	I-Disease
+ureter	I-Disease
+.	O
+
+Dapsone	B-Chemical
+-	O
+associated	O
+Heinz	O
+body	O
+hemolytic	B-Disease
+anemia	I-Disease
+in	O
+a	O
+Cambodian	O
+woman	O
+with	O
+hemoglobin	O
+E	O
+trait	O
+.	O
+
+A	O
+Cambodian	O
+woman	O
+with	O
+hemoglobin	O
+E	O
+trait	O
+(	O
+AE	O
+)	O
+and	O
+leprosy	B-Disease
+developed	O
+a	O
+Heinz	O
+body	O
+hemolytic	B-Disease
+anemia	I-Disease
+while	O
+taking	O
+a	O
+dose	O
+of	O
+dapsone	B-Chemical
+(	O
+50	O
+mg	O
+/	O
+day	O
+)	O
+not	O
+usually	O
+associated	O
+with	O
+clinical	O
+hemolysis	B-Disease
+.	O
+
+Her	O
+red	O
+blood	O
+cells	O
+(	O
+RBCs	O
+)	O
+had	O
+increased	O
+incubated	O
+Heinz	O
+body	O
+formation	O
+,	O
+decreased	O
+reduced	O
+glutathione	B-Chemical
+(	O
+GSH	B-Chemical
+)	O
+,	O
+and	O
+decreased	O
+GSH	B-Chemical
+stability	O
+.	O
+
+The	O
+pentose	B-Chemical
+phosphate	I-Chemical
+shunt	O
+activity	O
+of	O
+the	O
+dapsone	B-Chemical
+-	O
+exposed	O
+AE	O
+RBCs	O
+was	O
+increased	O
+compared	O
+to	O
+normal	O
+RBCs	O
+.	O
+
+Although	O
+the	O
+AE	O
+RBCs	O
+from	O
+an	O
+individual	O
+not	O
+taking	O
+dapsone	B-Chemical
+had	O
+increased	O
+incubated	O
+Heinz	O
+body	O
+formation	O
+,	O
+the	O
+GSH	B-Chemical
+content	O
+and	O
+GSH	B-Chemical
+stability	O
+were	O
+normal	O
+.	O
+
+The	O
+pentose	B-Chemical
+phosphate	I-Chemical
+shunt	O
+activity	O
+of	O
+the	O
+non	O
+-	O
+dapsone	B-Chemical
+-	O
+exposed	O
+AE	O
+RBCs	O
+was	O
+decreased	O
+compared	O
+to	O
+normal	O
+RBCs	O
+.	O
+
+Thus	O
+,	O
+AE	O
+RBCs	O
+appear	O
+to	O
+have	O
+an	O
+increased	O
+sensitivity	O
+to	O
+oxidant	O
+stress	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+,	O
+since	O
+dapsone	B-Chemical
+does	O
+not	O
+cause	O
+hemolytic	B-Disease
+anemia	I-Disease
+at	O
+this	O
+dose	O
+in	O
+hematologically	O
+normal	O
+individuals	O
+.	O
+
+Given	O
+the	O
+influx	O
+of	O
+Southeast	O
+Asians	O
+into	O
+the	O
+United	O
+States	O
+,	O
+oxidant	O
+medications	O
+should	O
+be	O
+used	O
+with	O
+caution	O
+,	O
+especially	O
+if	O
+an	O
+infection	B-Disease
+is	O
+present	O
+,	O
+in	O
+individuals	O
+of	O
+ethnic	O
+backgrounds	O
+that	O
+have	O
+an	O
+increased	O
+prevalence	O
+of	O
+hemoglobin	O
+E	O
+.	O
+
+Severe	O
+complications	O
+of	O
+antianginal	O
+drug	O
+therapy	O
+in	O
+a	O
+patient	O
+identified	O
+as	O
+a	O
+poor	O
+metabolizer	O
+of	O
+metoprolol	B-Chemical
+,	O
+propafenone	B-Chemical
+,	O
+diltiazem	B-Chemical
+,	O
+and	O
+sparteine	B-Chemical
+.	O
+
+A	O
+47	O
+-	O
+year	O
+-	O
+old	O
+patient	O
+suffering	O
+from	O
+coronary	B-Disease
+artery	I-Disease
+disease	I-Disease
+was	O
+admitted	O
+to	O
+the	O
+CCU	O
+in	O
+shock	B-Disease
+with	O
+III	O
+.	O
+
+AV	B-Disease
+block	I-Disease
+,	O
+severe	O
+hypotension	B-Disease
+,	O
+and	O
+impairment	B-Disease
+of	I-Disease
+ventricular	I-Disease
+function	I-Disease
+.	O
+
+One	O
+week	O
+prior	O
+to	O
+admission	O
+a	O
+therapy	O
+with	O
+standard	O
+doses	O
+of	O
+metoprolol	B-Chemical
+(	O
+100	O
+mg	O
+t	O
+.	O
+i	O
+.	O
+d	O
+.	O
+and	O
+then	O
+100	O
+mg	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+)	O
+had	O
+been	O
+initiated	O
+.	O
+
+Two	O
+days	O
+before	O
+admission	O
+diltiazem	B-Chemical
+(	O
+60	O
+mg	O
+b	O
+.	O
+i	O
+.	O
+d	O
+.	O
+)	O
+was	O
+prescribed	O
+in	O
+addition	O
+.	O
+
+Analyses	O
+of	O
+a	O
+blood	O
+sample	O
+revealed	O
+unusually	O
+high	O
+plasma	O
+concentrations	O
+of	O
+metoprolol	B-Chemical
+(	O
+greater	O
+than	O
+3000	O
+ng	O
+/	O
+ml	O
+)	O
+and	O
+diltiazem	B-Chemical
+(	O
+526	O
+ng	O
+/	O
+ml	O
+)	O
+.	O
+
+The	O
+patient	O
+recovered	O
+within	O
+1	O
+week	O
+following	O
+discontinuation	O
+of	O
+antianginal	O
+therapy	O
+.	O
+
+Three	O
+months	O
+later	O
+the	O
+patient	O
+was	O
+exposed	O
+to	O
+a	O
+single	O
+dose	O
+of	O
+metoprolol	B-Chemical
+,	O
+diltiazem	B-Chemical
+,	O
+propafenone	B-Chemical
+(	O
+since	O
+he	O
+had	O
+received	O
+this	O
+drug	O
+in	O
+the	O
+past	O
+)	O
+,	O
+and	O
+sparteine	B-Chemical
+(	O
+as	O
+a	O
+probe	O
+for	O
+the	O
+debrisoquine	B-Chemical
+/	O
+sparteine	B-Chemical
+type	O
+polymorphism	O
+of	O
+oxidative	O
+drug	O
+metabolism	O
+)	O
+.	O
+
+It	O
+was	O
+found	O
+that	O
+he	O
+was	O
+a	O
+poor	O
+metabolizer	O
+of	O
+all	O
+four	O
+drugs	O
+,	O
+indicating	O
+that	O
+their	O
+metabolism	O
+is	O
+under	O
+the	O
+same	O
+genetic	O
+control	O
+.	O
+
+Therefore	O
+,	O
+patients	O
+belonging	O
+to	O
+the	O
+poor	O
+-	O
+metabolizer	O
+phenotype	O
+of	O
+sparteine	B-Chemical
+/	O
+debrisoquine	B-Chemical
+polymorphism	O
+in	O
+drug	O
+metabolism	O
+,	O
+which	O
+constitutes	O
+6	O
+.	O
+4	O
+%	O
+of	O
+the	O
+German	O
+population	O
+,	O
+may	O
+experience	O
+adverse	B-Disease
+drug	I-Disease
+reactions	I-Disease
+when	O
+treated	O
+with	O
+standard	O
+doses	O
+of	O
+one	O
+of	O
+these	O
+drugs	O
+alone	O
+.	O
+
+Moreover	O
+,	O
+the	O
+coadministration	O
+of	O
+these	O
+frequently	O
+used	O
+drugs	O
+is	O
+expected	O
+to	O
+be	O
+especially	O
+harmful	O
+in	O
+this	O
+subgroup	O
+of	O
+patients	O
+.	O
+
+Clinical	O
+experiences	O
+in	O
+an	O
+open	O
+and	O
+a	O
+double	O
+-	O
+blind	O
+trial	O
+.	O
+
+A	O
+total	O
+of	O
+sixty	O
+patients	O
+were	O
+trated	O
+with	O
+bromperidol	B-Chemical
+first	O
+in	O
+open	O
+conditions	O
+(	O
+20	O
+patients	O
+)	O
+,	O
+then	O
+on	O
+a	O
+double	O
+blind	O
+basis	O
+(	O
+40	O
+patients	O
+)	O
+with	O
+haloperidol	B-Chemical
+as	O
+the	O
+reference	O
+substance	O
+.	O
+
+The	O
+open	O
+study	O
+lasted	O
+for	O
+four	O
+weeks	O
+;	O
+the	O
+drug	O
+was	O
+administrated	O
+in	O
+the	O
+form	O
+of	O
+1	O
+mg	O
+tablets	O
+.	O
+
+The	O
+daily	O
+dose	O
+(	O
+initial	O
+dose	O
+:	O
+1	O
+mg	O
+;	O
+mean	O
+dose	O
+at	O
+the	O
+end	O
+of	O
+the	O
+trial	O
+:	O
+4	O
+.	O
+47	O
+mg	O
+)	O
+was	O
+always	O
+administered	O
+in	O
+one	O
+single	O
+dose	O
+.	O
+
+Nineteen	O
+patients	O
+finished	O
+the	O
+trial	O
+,	O
+and	O
+in	O
+18	O
+cases	O
+the	O
+therapeutic	O
+result	O
+was	O
+considered	O
+very	O
+good	O
+to	O
+good	O
+.	O
+
+These	O
+results	O
+were	O
+confirmed	O
+by	O
+statistical	O
+analysis	O
+.	O
+
+Nine	O
+patients	O
+exhibited	O
+mild	O
+to	O
+moderate	O
+extrapyramidal	B-Disease
+concomitant	I-Disease
+symptoms	I-Disease
+;	O
+no	O
+other	O
+side	O
+effects	O
+were	O
+observed	O
+.	O
+
+The	O
+results	O
+of	O
+detailed	O
+laboratory	O
+tests	O
+and	O
+evaluations	O
+of	O
+various	O
+quantitative	O
+and	O
+qualitative	O
+tolerability	O
+parameters	O
+were	O
+not	O
+indicative	O
+of	O
+toxic	O
+effects	O
+.	O
+
+In	O
+the	O
+double	O
+blind	O
+study	O
+with	O
+haloperidol	B-Chemical
+,	O
+both	O
+substances	O
+were	O
+found	O
+to	O
+be	O
+highly	O
+effective	O
+in	O
+the	O
+treatment	O
+of	O
+psychotic	B-Disease
+syndromes	I-Disease
+belonging	I-Disease
+predominantly	I-Disease
+to	I-Disease
+the	I-Disease
+schizophrenia	I-Disease
+group	I-Disease
+.	O
+
+Certain	O
+clues	O
+,	O
+including	O
+the	O
+onset	O
+of	O
+action	O
+,	O
+seem	O
+to	O
+be	O
+indicative	O
+of	O
+the	O
+superiority	O
+of	O
+bromperidol	B-Chemical
+.	O
+
+No	O
+differences	O
+were	O
+observed	O
+with	O
+respect	O
+to	O
+side	O
+effects	O
+and	O
+general	O
+tolerability	O
+.	O
+
+Prolonged	O
+cholestasis	B-Disease
+after	O
+troleandomycin	B-Chemical
+-	O
+induced	O
+acute	O
+hepatitis	B-Disease
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+patient	O
+in	O
+whom	O
+troleandomycin	B-Chemical
+-	O
+induced	O
+hepatitis	B-Disease
+was	O
+followed	O
+by	O
+prolonged	O
+anicteric	O
+cholestasis	B-Disease
+.	O
+
+Jaundice	B-Disease
+occurred	O
+after	O
+administration	O
+of	O
+troleandomycin	B-Chemical
+for	O
+7	O
+days	O
+and	O
+was	O
+associated	O
+with	O
+hypereosinophilia	B-Disease
+.	O
+
+Jaundice	B-Disease
+disappeared	O
+within	O
+3	O
+months	O
+but	O
+was	O
+followed	O
+by	O
+prolonged	O
+anicteric	O
+cholestasis	B-Disease
+marked	O
+by	O
+pruritus	B-Disease
+and	O
+high	O
+levels	O
+of	O
+alkaline	O
+phosphatase	O
+and	O
+gammaglutamyltransferase	O
+activities	O
+.	O
+
+Finally	O
+,	O
+pruritus	B-Disease
+disappeared	O
+within	O
+19	O
+months	O
+,	O
+and	O
+liver	O
+tests	O
+returned	O
+to	O
+normal	O
+27	O
+months	O
+after	O
+the	O
+onset	O
+of	O
+hepatitis	B-Disease
+.	O
+
+This	O
+observation	O
+demonstrates	O
+that	O
+prolonged	O
+cholestasis	B-Disease
+can	O
+follow	O
+troleandomycin	B-Chemical
+-	O
+induced	O
+acute	O
+hepatitis	B-Disease
+.	O
+
+Serial	O
+studies	O
+of	O
+auditory	B-Disease
+neurotoxicity	I-Disease
+in	O
+patients	O
+receiving	O
+deferoxamine	B-Chemical
+therapy	O
+.	O
+
+Visual	B-Disease
+and	I-Disease
+auditory	I-Disease
+neurotoxicity	I-Disease
+was	O
+previously	O
+documented	O
+in	O
+42	O
+of	O
+89	O
+patients	O
+with	O
+transfusion	O
+-	O
+dependent	O
+anemia	B-Disease
+who	O
+were	O
+receiving	O
+iron	B-Chemical
+chelation	O
+therapy	O
+with	O
+daily	O
+subcutaneous	O
+deferoxamine	B-Chemical
+.	O
+
+Twenty	O
+-	O
+two	O
+patients	O
+in	O
+the	O
+affected	O
+group	O
+had	O
+abnormal	B-Disease
+audiograms	I-Disease
+with	I-Disease
+deficits	I-Disease
+mostly	I-Disease
+in	I-Disease
+the	I-Disease
+high	I-Disease
+frequency	I-Disease
+range	I-Disease
+of	I-Disease
+4	I-Disease
+,	I-Disease
+000	I-Disease
+to	I-Disease
+8	I-Disease
+,	I-Disease
+000	I-Disease
+Hz	I-Disease
+and	O
+in	O
+the	O
+hearing	O
+threshold	O
+levels	O
+of	O
+30	O
+to	O
+100	O
+decibels	O
+.	O
+
+When	O
+deferoxamine	B-Chemical
+therapy	O
+was	O
+discontinued	O
+and	O
+serial	O
+studies	O
+were	O
+performed	O
+,	O
+audiograms	O
+in	O
+seven	O
+cases	O
+reverted	O
+to	O
+normal	O
+or	O
+near	O
+normal	O
+within	O
+two	O
+to	O
+three	O
+weeks	O
+,	O
+and	O
+nine	O
+of	O
+13	O
+patients	O
+with	O
+symptoms	O
+became	O
+asymptomatic	O
+.	O
+
+Audiograms	O
+from	O
+15	O
+patients	O
+remained	O
+abnormal	O
+and	O
+four	O
+patients	O
+required	O
+hearing	O
+aids	O
+because	O
+of	O
+permanent	B-Disease
+disability	I-Disease
+.	O
+
+Since	O
+18	O
+of	O
+the	O
+22	O
+patients	O
+were	O
+initially	O
+receiving	O
+deferoxamine	B-Chemical
+doses	O
+in	O
+excess	O
+of	O
+the	O
+commonly	O
+recommended	O
+50	O
+mg	O
+/	O
+kg	O
+per	O
+dose	O
+,	O
+therapy	O
+was	O
+restarted	O
+with	O
+lower	O
+doses	O
+,	O
+usually	O
+50	O
+mg	O
+/	O
+kg	O
+per	O
+dose	O
+or	O
+less	O
+depending	O
+on	O
+the	O
+degree	O
+of	O
+auditory	B-Disease
+abnormality	I-Disease
+,	O
+and	O
+with	O
+the	O
+exception	O
+of	O
+two	O
+cases	O
+no	O
+further	O
+toxicity	B-Disease
+was	O
+demonstrated	O
+.	O
+
+Auditory	O
+deterioration	O
+and	O
+improvement	O
+,	O
+demonstrated	O
+serially	O
+in	O
+individual	O
+patients	O
+receiving	O
+and	O
+not	O
+receiving	O
+deferoxamine	B-Chemical
+,	O
+respectively	O
+,	O
+provided	O
+convincing	O
+evidence	O
+for	O
+a	O
+cause	O
+-	O
+and	O
+-	O
+effect	O
+relation	O
+between	O
+deferoxamine	B-Chemical
+administration	O
+and	O
+ototoxicity	B-Disease
+.	O
+
+Based	O
+on	O
+these	O
+data	O
+,	O
+a	O
+plan	O
+of	O
+management	O
+was	O
+developed	O
+that	O
+allows	O
+effective	O
+yet	O
+safe	O
+administration	O
+of	O
+deferoxamine	B-Chemical
+.	O
+
+A	O
+dose	O
+of	O
+50	O
+mg	O
+/	O
+kg	O
+is	O
+recommended	O
+in	O
+those	O
+without	O
+audiogram	O
+abnormalities	O
+.	O
+
+With	O
+mild	O
+toxicity	B-Disease
+,	O
+a	O
+reduction	O
+to	O
+30	O
+or	O
+40	O
+mg	O
+/	O
+kg	O
+per	O
+dose	O
+should	O
+result	O
+in	O
+a	O
+reversal	O
+of	O
+the	O
+abnormal	O
+results	O
+to	O
+normal	O
+within	O
+four	O
+weeks	O
+.	O
+
+Moderate	O
+abnormalities	O
+require	O
+a	O
+reduction	O
+of	O
+deferoxamine	B-Chemical
+to	O
+25	O
+mg	O
+/	O
+kg	O
+per	O
+dose	O
+with	O
+careful	O
+monitoring	O
+.	O
+
+In	O
+those	O
+with	O
+symptoms	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+,	O
+the	O
+drug	O
+should	O
+be	O
+stopped	O
+for	O
+four	O
+weeks	O
+,	O
+and	O
+when	O
+the	O
+audiogram	O
+is	O
+stable	O
+or	O
+improved	O
+,	O
+therapy	O
+should	O
+be	O
+restarted	O
+at	O
+10	O
+to	O
+25	O
+mg	O
+/	O
+kg	O
+per	O
+dose	O
+.	O
+
+Serial	O
+audiograms	O
+should	O
+be	O
+performed	O
+every	O
+six	O
+months	O
+in	O
+those	O
+without	O
+problems	O
+and	O
+more	O
+frequently	O
+in	O
+young	O
+patients	O
+with	O
+normal	O
+serum	O
+ferritin	O
+values	O
+and	O
+in	O
+those	O
+with	O
+auditory	B-Disease
+dysfunction	I-Disease
+.	O
+
+Lidocaine	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+asystole	I-Disease
+.	O
+
+Intravenous	O
+administration	O
+of	O
+a	O
+single	O
+50	O
+-	O
+mg	O
+bolus	O
+of	O
+lidocaine	B-Chemical
+in	O
+a	O
+67	O
+-	O
+year	O
+-	O
+old	O
+man	O
+resulted	O
+in	O
+profound	O
+depression	B-Disease
+of	O
+the	O
+activity	O
+of	O
+the	O
+sinoatrial	O
+and	O
+atrioventricular	O
+nodal	O
+pacemakers	O
+.	O
+
+The	O
+patient	O
+had	O
+no	O
+apparent	O
+associated	O
+conditions	O
+which	O
+might	O
+have	O
+predisposed	O
+him	O
+to	O
+the	O
+development	O
+of	O
+bradyarrhythmias	B-Disease
+;	O
+and	O
+,	O
+thus	O
+,	O
+this	O
+probably	O
+represented	O
+a	O
+true	O
+idiosyncrasy	O
+to	O
+lidocaine	B-Chemical
+.	O
+
+Flurbiprofen	B-Chemical
+in	O
+the	O
+treatment	O
+of	O
+juvenile	B-Disease
+rheumatoid	I-Disease
+arthritis	I-Disease
+.	O
+
+Thirty	O
+-	O
+four	O
+patients	O
+with	O
+juvenile	B-Disease
+rheumatoid	I-Disease
+arthritis	I-Disease
+,	O
+who	O
+were	O
+treated	O
+with	O
+flurbiprofen	B-Chemical
+at	O
+a	O
+maximum	O
+dose	O
+of	O
+4	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+,	O
+had	O
+statistically	O
+significant	O
+decreases	O
+from	O
+baseline	O
+in	O
+6	O
+arthritis	B-Disease
+indices	O
+after	O
+12	O
+weeks	O
+of	O
+treatment	O
+.	O
+
+Improvements	O
+were	O
+seen	O
+in	O
+the	O
+number	O
+of	O
+tender	B-Disease
+joints	I-Disease
+,	O
+the	O
+severity	O
+of	O
+swelling	B-Disease
+and	O
+tenderness	B-Disease
+,	O
+the	O
+time	O
+of	O
+walk	O
+50	O
+feet	O
+,	O
+the	O
+duration	O
+of	O
+morning	B-Disease
+stiffness	I-Disease
+and	O
+the	O
+circumference	O
+of	O
+the	O
+left	O
+knee	O
+.	O
+
+The	O
+most	O
+frequently	O
+observed	O
+side	O
+effect	O
+was	O
+fecal	B-Disease
+occult	I-Disease
+blood	I-Disease
+(	O
+25	O
+%	O
+of	O
+patients	O
+)	O
+;	O
+however	O
+,	O
+there	O
+was	O
+no	O
+other	O
+evidence	O
+of	O
+gastrointestinal	B-Disease
+(	I-Disease
+GI	I-Disease
+)	I-Disease
+bleeding	I-Disease
+in	O
+these	O
+patients	O
+.	O
+
+One	O
+patient	O
+was	O
+prematurely	O
+discontinued	O
+from	O
+the	O
+study	O
+for	O
+severe	O
+headache	B-Disease
+and	O
+abdominal	B-Disease
+pain	I-Disease
+.	O
+
+Most	O
+side	O
+effects	O
+were	O
+mild	O
+and	O
+related	O
+to	O
+the	O
+GI	O
+tract	O
+.	O
+
+Hyperkalemia	B-Disease
+associated	O
+with	O
+sulindac	B-Chemical
+therapy	O
+.	O
+
+Hyperkalemia	B-Disease
+has	O
+recently	O
+been	O
+recognized	O
+as	O
+a	O
+complication	O
+of	O
+nonsteroidal	O
+antiinflammatory	O
+agents	O
+(	O
+NSAID	O
+)	O
+such	O
+as	O
+indomethacin	B-Chemical
+.	O
+
+Several	O
+recent	O
+studies	O
+have	O
+stressed	O
+the	O
+renal	O
+sparing	O
+features	O
+of	O
+sulindac	B-Chemical
+,	O
+owing	O
+to	O
+its	O
+lack	O
+of	O
+interference	O
+with	O
+renal	O
+prostacyclin	B-Chemical
+synthesis	O
+.	O
+
+We	O
+describe	O
+4	O
+patients	O
+in	O
+whom	O
+hyperkalemia	B-Disease
+ranging	O
+from	O
+6	O
+.	O
+1	O
+to	O
+6	O
+.	O
+9	O
+mEq	O
+/	O
+l	O
+developed	O
+within	O
+3	O
+to	O
+8	O
+days	O
+of	O
+sulindac	B-Chemical
+administration	O
+.	O
+
+In	O
+all	O
+of	O
+them	O
+normal	O
+serum	O
+potassium	B-Chemical
+levels	O
+reached	O
+within	O
+2	O
+to	O
+4	O
+days	O
+of	O
+stopping	O
+sulindac	B-Chemical
+.	O
+
+As	O
+no	O
+other	O
+medications	O
+known	O
+to	O
+effect	O
+serum	O
+potassium	B-Chemical
+had	O
+been	O
+given	O
+concomitantly	O
+,	O
+this	O
+course	O
+of	O
+events	O
+is	O
+suggestive	O
+of	O
+a	O
+cause	O
+-	O
+and	O
+-	O
+effect	O
+relationship	O
+between	O
+sulindac	B-Chemical
+and	O
+hyperkalemia	B-Disease
+.	O
+
+These	O
+observations	O
+indicate	O
+that	O
+initial	O
+hopes	O
+that	O
+sulindac	B-Chemical
+may	O
+not	O
+be	O
+associated	O
+with	O
+the	O
+adverse	O
+renal	O
+effects	O
+of	O
+other	O
+NSAID	O
+are	O
+probably	O
+not	O
+justified	O
+.	O
+
+Drug	O
+-	O
+induced	O
+arterial	O
+spasm	B-Disease
+relieved	O
+by	O
+lidocaine	B-Chemical
+.	O
+
+Case	O
+report	O
+.	O
+
+Following	O
+major	O
+intracranial	O
+surgery	O
+in	O
+a	O
+35	O
+-	O
+year	O
+-	O
+old	O
+man	O
+,	O
+sodium	B-Chemical
+pentothal	I-Chemical
+was	O
+intravenously	O
+infused	O
+to	O
+minimize	O
+cerebral	B-Disease
+ischaemia	I-Disease
+.	O
+
+Intense	O
+vasospasm	B-Disease
+with	O
+threatened	O
+gangrene	B-Disease
+arose	O
+in	O
+the	O
+arm	O
+used	O
+for	O
+the	O
+infusion	O
+.	O
+
+Since	O
+the	O
+cranial	O
+condition	O
+precluded	O
+use	O
+of	O
+more	O
+usual	O
+methods	O
+,	O
+lidocaine	B-Chemical
+was	O
+given	O
+intra	O
+-	O
+arterially	O
+,	O
+with	O
+careful	O
+cardiovascular	O
+monitoring	O
+,	O
+to	O
+counteract	O
+the	O
+vasospasm	B-Disease
+.	O
+
+The	O
+treatment	O
+was	O
+rapidly	O
+successful	O
+.	O
+
+Regional	O
+localization	O
+of	O
+the	O
+antagonism	O
+of	O
+amphetamine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+by	O
+intracerebral	O
+calcitonin	B-Chemical
+injections	O
+.	O
+
+Calcitonin	B-Chemical
+receptors	O
+are	O
+found	O
+in	O
+the	O
+brain	O
+,	O
+and	O
+intracerebral	O
+infusions	O
+of	O
+calcitonin	B-Chemical
+can	O
+produce	O
+behavioral	O
+effects	O
+.	O
+
+Among	O
+these	O
+behavioral	O
+effects	O
+are	O
+decreases	O
+in	O
+food	O
+intake	O
+and	O
+decreases	O
+in	O
+amphetamine	B-Chemical
+-	O
+induced	O
+locomotor	O
+activity	O
+.	O
+
+In	O
+previous	O
+experiments	O
+we	O
+found	O
+that	O
+decreases	O
+in	O
+food	O
+intake	O
+were	O
+induced	O
+by	O
+local	O
+administration	O
+of	O
+calcitonin	B-Chemical
+into	O
+several	O
+hypothalamic	O
+sites	O
+and	O
+into	O
+the	O
+nucleus	O
+accumbens	O
+.	O
+
+In	O
+the	O
+present	O
+experiment	O
+calcitonin	B-Chemical
+decreased	O
+locomotor	O
+activity	O
+when	O
+locally	O
+injected	O
+into	O
+the	O
+same	O
+sites	O
+where	O
+it	O
+decreases	O
+food	O
+intake	O
+.	O
+
+The	O
+areas	O
+where	O
+calcitonin	B-Chemical
+is	O
+most	O
+effective	O
+in	O
+decreasing	O
+locomotor	O
+activity	O
+are	O
+located	O
+in	O
+the	O
+hypothalamus	O
+and	O
+nucleus	O
+accumbens	O
+,	O
+suggesting	O
+that	O
+these	O
+areas	O
+are	O
+the	O
+major	O
+sites	O
+of	O
+action	O
+of	O
+calcitonin	B-Chemical
+in	O
+inhibiting	O
+amphetamine	B-Chemical
+-	O
+induced	O
+locomotor	O
+activity	O
+.	O
+
+The	O
+hematologic	O
+effects	O
+of	O
+cefonicid	B-Chemical
+and	O
+cefazedone	B-Chemical
+in	O
+the	O
+dog	O
+:	O
+a	O
+potential	O
+model	O
+of	O
+cephalosporin	B-Chemical
+hematotoxicity	B-Disease
+in	O
+man	O
+.	O
+
+Cephalosporin	B-Chemical
+antibiotics	O
+cause	O
+a	O
+variety	O
+of	O
+hematologic	B-Disease
+disturbances	I-Disease
+in	O
+man	O
+,	O
+the	O
+pathogeneses	O
+and	O
+hematopathology	O
+of	O
+which	O
+remain	O
+poorly	O
+characterized	O
+.	O
+
+There	O
+is	O
+a	O
+need	O
+for	O
+a	O
+well	O
+-	O
+defined	O
+animal	O
+model	O
+in	O
+which	O
+these	O
+blood	B-Disease
+dyscrasias	I-Disease
+can	O
+be	O
+studied	O
+.	O
+
+In	O
+four	O
+subacute	O
+toxicity	B-Disease
+studies	O
+,	O
+the	O
+intravenous	O
+administration	O
+of	O
+cefonicid	B-Chemical
+or	O
+cefazedone	B-Chemical
+to	O
+beagle	O
+dogs	O
+caused	O
+a	O
+dose	O
+-	O
+dependent	O
+incidence	O
+of	O
+anemia	B-Disease
+,	O
+neutropenia	B-Disease
+,	O
+and	O
+thrombocytopenia	B-Disease
+after	O
+1	O
+-	O
+3	O
+months	O
+of	O
+treatment	O
+.	O
+
+A	O
+nonregenerative	O
+anemia	B-Disease
+was	O
+the	O
+most	O
+compromising	O
+of	O
+the	O
+cytopenias	B-Disease
+and	O
+occurred	O
+in	O
+approximately	O
+50	O
+%	O
+of	O
+dogs	O
+receiving	O
+400	O
+-	O
+500	O
+mg	O
+/	O
+kg	O
+cefonicid	B-Chemical
+or	O
+540	O
+-	O
+840	O
+mg	O
+/	O
+kg	O
+cefazedone	B-Chemical
+.	O
+
+All	O
+three	O
+cytopenias	B-Disease
+were	O
+completely	O
+reversible	O
+following	O
+cessation	O
+of	O
+treatment	O
+;	O
+the	O
+time	O
+required	O
+for	O
+recovery	O
+of	O
+the	O
+erythron	O
+(	O
+approximately	O
+1	O
+month	O
+)	O
+was	O
+considerably	O
+longer	O
+than	O
+that	O
+of	O
+the	O
+granulocytes	O
+and	O
+platelets	O
+(	O
+hours	O
+to	O
+a	O
+few	O
+days	O
+)	O
+.	O
+
+Upon	O
+rechallenge	O
+with	O
+either	O
+cephalosporin	B-Chemical
+,	O
+the	O
+hematologic	B-Disease
+syndrome	I-Disease
+was	O
+reproduced	O
+in	O
+most	O
+dogs	O
+tested	O
+;	O
+cefonicid	B-Chemical
+(	O
+but	O
+not	O
+cefazedone	B-Chemical
+)	O
+-	O
+treated	O
+dogs	O
+showed	O
+a	O
+substantially	O
+reduced	O
+induction	O
+period	O
+(	O
+15	O
++	O
+/	O
+-	O
+5	O
+days	O
+)	O
+compared	O
+to	O
+that	O
+of	O
+the	O
+first	O
+exposure	O
+to	O
+the	O
+drug	O
+(	O
+61	O
++	O
+/	O
+-	O
+24	O
+days	O
+)	O
+.	O
+
+This	O
+observation	O
+,	O
+along	O
+with	O
+the	O
+rapid	O
+rate	O
+of	O
+decline	O
+in	O
+red	O
+cell	O
+mass	O
+parameters	O
+of	O
+affected	O
+dogs	O
+,	O
+suggests	O
+that	O
+a	O
+hemolytic	B-Disease
+component	O
+complicated	O
+the	O
+red	O
+cell	O
+production	O
+problem	O
+and	O
+that	O
+multiple	O
+toxicologic	O
+mechanisms	O
+contributed	O
+to	O
+the	O
+cytopenia	B-Disease
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+administration	O
+of	O
+high	O
+doses	O
+of	O
+cefonicid	B-Chemical
+or	O
+cefazedone	B-Chemical
+to	O
+dogs	O
+can	O
+induce	O
+hematotoxicity	B-Disease
+similar	O
+to	O
+the	O
+cephalosporin	B-Chemical
+-	O
+induced	O
+blood	B-Disease
+dyscrasias	I-Disease
+described	O
+in	O
+man	O
+and	O
+thus	O
+provides	O
+a	O
+useful	O
+model	O
+for	O
+studying	O
+the	O
+mechanisms	O
+of	O
+these	O
+disorders	O
+.	O
+
+Cerebral	O
+blood	O
+flow	O
+and	O
+metabolism	O
+during	O
+isoflurane	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+in	O
+patients	O
+subjected	O
+to	O
+surgery	O
+for	O
+cerebral	B-Disease
+aneurysms	I-Disease
+.	O
+
+Cerebral	O
+blood	O
+flow	O
+and	O
+cerebral	O
+metabolic	O
+rate	O
+for	O
+oxygen	B-Chemical
+were	O
+measured	O
+during	O
+isoflurane	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+in	O
+10	O
+patients	O
+subjected	O
+to	O
+craniotomy	O
+for	O
+clipping	O
+of	O
+a	O
+cerebral	B-Disease
+aneurysm	I-Disease
+.	O
+
+Flow	O
+and	O
+metabolism	O
+were	O
+measured	O
+5	O
+-	O
+13	O
+days	O
+after	O
+the	O
+subarachnoid	B-Disease
+haemorrhage	I-Disease
+by	O
+a	O
+modification	O
+of	O
+the	O
+classical	O
+Kety	O
+-	O
+Schmidt	O
+technique	O
+using	O
+xenon	B-Chemical
+-	O
+133	O
+i	O
+.	O
+v	O
+.	O
+Anaesthesia	O
+was	O
+maintained	O
+with	O
+an	O
+inspired	O
+isoflurane	B-Chemical
+concentration	O
+of	O
+0	O
+.	O
+75	O
+%	O
+(	O
+plus	O
+67	O
+%	O
+nitrous	B-Chemical
+oxide	I-Chemical
+in	O
+oxygen	B-Chemical
+)	O
+,	O
+during	O
+which	O
+CBF	O
+and	O
+CMRO2	O
+were	O
+34	O
+.	O
+3	O
++	O
+/	O
+-	O
+2	O
+.	O
+1	O
+ml	O
+/	O
+100	O
+g	O
+min	O
+-	O
+1	O
+and	O
+2	O
+.	O
+32	O
++	O
+/	O
+-	O
+0	O
+.	O
+16	O
+ml	O
+/	O
+100	O
+g	O
+min	O
+-	O
+1	O
+at	O
+PaCO2	O
+4	O
+.	O
+1	O
++	O
+/	O
+-	O
+0	O
+.	O
+1	O
+kPa	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SEM	O
+)	O
+.	O
+
+Controlled	O
+hypotension	B-Disease
+to	O
+an	O
+average	O
+MAP	O
+of	O
+50	O
+-	O
+55	O
+mm	O
+Hg	B-Chemical
+was	O
+induced	O
+by	O
+increasing	O
+the	O
+dose	O
+of	O
+isoflurane	B-Chemical
+,	O
+and	O
+maintained	O
+at	O
+an	O
+inspired	O
+concentration	O
+of	O
+2	O
+.	O
+2	O
++	O
+/	O
+-	O
+0	O
+.	O
+2	O
+%	O
+.	O
+
+This	O
+resulted	O
+in	O
+a	O
+significant	O
+decrease	O
+in	O
+CMRO2	O
+(	O
+to	O
+1	O
+.	O
+73	O
++	O
+/	O
+-	O
+0	O
+.	O
+16	O
+ml	O
+/	O
+100	O
+g	O
+min	O
+-	O
+1	O
+)	O
+,	O
+while	O
+CBF	O
+was	O
+unchanged	O
+.	O
+
+After	O
+the	O
+clipping	O
+of	O
+the	O
+aneurysm	B-Disease
+the	O
+isoflurane	B-Chemical
+concentration	O
+was	O
+reduced	O
+to	O
+0	O
+.	O
+75	O
+%	O
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+increase	O
+in	O
+CBF	O
+,	O
+although	O
+CMRO2	O
+was	O
+unchanged	O
+,	O
+compared	O
+with	O
+pre	O
+-	O
+hypotensive	B-Disease
+values	O
+.	O
+
+These	O
+changes	O
+might	O
+offer	O
+protection	O
+to	O
+brain	O
+tissue	O
+during	O
+periods	O
+of	O
+induced	O
+hypotension	B-Disease
+.	O
+
+Triazolam	B-Chemical
+-	O
+induced	O
+brief	O
+episodes	O
+of	O
+secondary	O
+mania	B-Disease
+in	O
+a	O
+depressed	B-Disease
+patient	O
+.	O
+
+Large	O
+doses	O
+of	O
+triazolam	B-Chemical
+repeatedly	O
+induced	O
+brief	O
+episodes	O
+of	O
+mania	B-Disease
+in	O
+a	O
+depressed	B-Disease
+elderly	O
+woman	O
+.	O
+
+Features	O
+of	O
+organic	B-Disease
+mental	I-Disease
+disorder	I-Disease
+(	O
+delirium	B-Disease
+)	O
+were	O
+not	O
+present	O
+.	O
+
+Manic	B-Disease
+excitement	O
+was	O
+coincident	O
+with	O
+the	O
+duration	O
+of	O
+action	O
+of	O
+triazolam	B-Chemical
+.	O
+
+The	O
+possible	O
+contribution	O
+of	O
+the	O
+triazolo	B-Chemical
+group	O
+to	O
+changes	O
+in	O
+affective	O
+status	O
+is	O
+discussed	O
+.	O
+
+The	O
+correlation	O
+between	O
+neurotoxic	B-Disease
+esterase	O
+inhibition	O
+and	O
+mipafox	B-Chemical
+-	O
+induced	O
+neuropathic	B-Disease
+damage	I-Disease
+in	O
+rats	O
+.	O
+
+The	O
+correlation	O
+between	O
+neuropathic	B-Disease
+damage	I-Disease
+and	O
+inhibition	O
+of	O
+neurotoxic	B-Disease
+esterase	O
+or	O
+neuropathy	B-Disease
+target	O
+enzyme	O
+(	O
+NTE	O
+)	O
+was	O
+examined	O
+in	O
+rats	O
+acutely	O
+exposed	O
+to	O
+Mipafox	B-Chemical
+(	O
+N	B-Chemical
+,	I-Chemical
+N	I-Chemical
+'	I-Chemical
+-	I-Chemical
+diisopropylphosphorodiamidofluoridate	I-Chemical
+)	O
+,	O
+a	O
+neurotoxic	B-Disease
+organophosphate	B-Chemical
+.	O
+
+Brain	O
+and	O
+spinal	O
+cord	O
+NTE	O
+activities	O
+were	O
+measured	O
+in	O
+Long	O
+-	O
+Evans	O
+male	O
+rats	O
+1	O
+hr	O
+post	O
+-	O
+exposure	O
+to	O
+various	O
+dosages	O
+of	O
+Mipafox	B-Chemical
+(	O
+ip	O
+,	O
+1	O
+-	O
+15	O
+mg	O
+/	O
+kg	O
+)	O
+.	O
+
+These	O
+data	O
+were	O
+correlated	O
+with	O
+histologically	O
+scored	O
+cervical	O
+cord	B-Disease
+damage	I-Disease
+in	O
+a	O
+separate	O
+group	O
+of	O
+similarly	O
+dosed	O
+rats	O
+sampled	O
+14	O
+-	O
+21	O
+days	O
+post	O
+-	O
+exposure	O
+.	O
+
+Those	O
+dosages	O
+(	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+10	O
+mg	O
+/	O
+kg	O
+)	O
+that	O
+inhibited	O
+mean	O
+NTE	O
+activity	O
+in	O
+the	O
+spinal	O
+cord	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+73	O
+%	O
+and	O
+brain	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+67	O
+%	O
+of	O
+control	O
+values	O
+produced	O
+severe	O
+(	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+3	O
+)	O
+cervical	O
+cord	O
+pathology	O
+in	O
+85	O
+%	O
+of	O
+the	O
+rats	O
+.	O
+
+In	O
+contrast	O
+,	O
+dosages	O
+of	O
+Mipafox	B-Chemical
+(	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+which	O
+inhibited	O
+mean	O
+NTE	O
+activity	O
+in	O
+spinal	O
+cord	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+61	O
+%	O
+and	O
+brain	O
+less	O
+than	O
+or	O
+equal	O
+to	O
+60	O
+%	O
+produced	O
+this	O
+degree	O
+of	O
+cord	B-Disease
+damage	I-Disease
+in	O
+only	O
+9	O
+%	O
+of	O
+the	O
+animals	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+a	O
+critical	O
+percentage	O
+of	O
+NTE	O
+inhibition	O
+in	O
+brain	O
+and	O
+spinal	O
+cord	O
+sampled	O
+shortly	O
+after	O
+Mipafox	B-Chemical
+exposure	O
+can	O
+predict	O
+neuropathic	B-Disease
+damage	I-Disease
+in	O
+rats	O
+several	O
+weeks	O
+later	O
+.	O
+
+Allergic	B-Disease
+reaction	I-Disease
+to	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+infusion	O
+.	O
+
+An	O
+allergic	B-Disease
+reaction	I-Disease
+consisting	O
+of	O
+angioneurotic	B-Disease
+edema	I-Disease
+secondary	O
+to	O
+continuous	O
+infusion	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+occurred	O
+in	O
+a	O
+patient	O
+with	O
+recurrent	O
+carcinoma	B-Disease
+of	I-Disease
+the	I-Disease
+oral	I-Disease
+cavity	I-Disease
+,	O
+cirrhosis	B-Disease
+,	O
+and	O
+cisplatin	B-Chemical
+-	O
+induced	O
+impaired	B-Disease
+renal	I-Disease
+function	I-Disease
+.	O
+
+This	O
+reaction	O
+occurred	O
+during	O
+the	O
+sixth	O
+and	O
+seventh	O
+courses	O
+of	O
+infusional	O
+chemotherapy	O
+.	O
+
+Oral	O
+diphenhydramine	B-Chemical
+and	O
+prednisone	B-Chemical
+were	O
+ineffective	O
+in	O
+preventing	O
+the	O
+recurrence	O
+of	O
+the	O
+allergic	B-Disease
+reaction	I-Disease
+.	O
+
+Discontinuance	O
+of	O
+effective	O
+chemotherapy	O
+in	O
+this	O
+patient	O
+during	O
+partial	O
+remission	O
+resulted	O
+in	O
+fatal	O
+disease	O
+progression	O
+.	O
+
+Myasthenia	B-Disease
+gravis	I-Disease
+caused	O
+by	O
+penicillamine	B-Chemical
+and	O
+chloroquine	B-Chemical
+therapy	O
+for	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+.	O
+
+We	O
+have	O
+described	O
+a	O
+unique	O
+patient	O
+who	O
+had	O
+reversible	O
+and	O
+dose	O
+-	O
+related	O
+myasthenia	B-Disease
+gravis	I-Disease
+after	O
+penicillamine	B-Chemical
+and	O
+chloroquine	B-Chemical
+therapy	O
+for	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+.	O
+
+Although	O
+acetylcholine	B-Chemical
+receptor	O
+antibodies	O
+were	O
+not	O
+detectable	O
+,	O
+the	O
+time	O
+course	O
+was	O
+consistent	O
+with	O
+an	O
+autoimmune	O
+process	O
+.	O
+
+On	O
+the	O
+mechanisms	O
+of	O
+the	O
+development	O
+of	O
+tolerance	O
+to	O
+the	O
+muscular	B-Disease
+rigidity	I-Disease
+produced	O
+by	O
+morphine	B-Chemical
+in	O
+rats	O
+.	O
+
+The	O
+development	O
+of	O
+tolerance	O
+to	O
+the	O
+muscular	B-Disease
+rigidity	I-Disease
+produced	O
+by	O
+morphine	B-Chemical
+was	O
+studied	O
+in	O
+rats	O
+.	O
+
+Saline	O
+-	O
+pretreated	O
+controls	O
+given	O
+a	O
+test	O
+dose	O
+of	O
+morphine	B-Chemical
+(	O
+20	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+showed	O
+a	O
+pronounced	O
+rigidity	B-Disease
+recorded	O
+as	O
+tonic	O
+activity	O
+in	O
+the	O
+electromyogram	O
+.	O
+
+Rats	O
+treated	O
+for	O
+11	O
+days	O
+with	O
+morphine	B-Chemical
+and	O
+withdrawn	O
+for	O
+36	O
+-	O
+40	O
+h	O
+showed	O
+differences	O
+in	O
+the	O
+development	O
+of	O
+tolerance	O
+:	O
+about	O
+half	O
+of	O
+the	O
+animals	O
+showed	O
+a	O
+rigidity	B-Disease
+after	O
+the	O
+test	O
+dose	O
+of	O
+morphine	B-Chemical
+that	O
+was	O
+not	O
+significantly	O
+less	O
+than	O
+in	O
+the	O
+controls	O
+and	O
+were	O
+akinetic	B-Disease
+(	O
+A	O
+group	O
+)	O
+.	O
+
+The	O
+other	O
+rats	O
+showed	O
+a	O
+strong	O
+decrease	O
+in	O
+the	O
+rigidity	B-Disease
+and	O
+the	O
+occurrence	O
+of	O
+stereotyped	O
+(	O
+S	O
+)	O
+licking	O
+and	O
+/	O
+or	O
+gnawing	O
+in	O
+presence	O
+of	O
+akinetic	B-Disease
+or	O
+hyperkinetic	B-Disease
+(	O
+K	O
+)	O
+behaviour	O
+(	O
+AS	O
+/	O
+KS	O
+group	O
+)	O
+,	O
+suggesting	O
+signs	O
+of	O
+dopaminergic	O
+activation	O
+.	O
+
+The	O
+rigidity	B-Disease
+was	O
+considerably	O
+decreased	O
+in	O
+both	O
+groups	O
+after	O
+20	O
+days	O
+'	O
+treatment	O
+.	O
+
+In	O
+a	O
+further	O
+series	O
+of	O
+experiments	O
+,	O
+haloperidol	B-Chemical
+(	O
+0	O
+.	O
+2	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+p	O
+.	O
+)	O
+was	O
+used	O
+in	O
+order	O
+to	O
+block	O
+the	O
+dopaminergic	O
+activation	O
+and	O
+to	O
+estimate	O
+the	O
+real	O
+degree	O
+of	O
+the	O
+tolerance	O
+to	O
+the	O
+rigidity	B-Disease
+without	O
+any	O
+dopaminergic	O
+interference	O
+.	O
+
+Haloperidol	B-Chemical
+enhanced	O
+the	O
+rigidity	B-Disease
+in	O
+the	O
+A	O
+group	O
+.	O
+
+However	O
+,	O
+the	O
+level	O
+in	O
+the	O
+AS	O
+/	O
+KS	O
+group	O
+remained	O
+considerably	O
+lower	O
+than	O
+in	O
+the	O
+A	O
+group	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+rigidity	B-Disease
+,	O
+which	O
+is	O
+assumed	O
+to	O
+be	O
+due	O
+to	O
+an	O
+action	O
+of	O
+morphine	B-Chemical
+in	O
+the	O
+striatum	O
+,	O
+can	O
+be	O
+antagonized	O
+by	O
+another	O
+process	O
+leading	O
+to	O
+dopaminergic	O
+activation	O
+in	O
+the	O
+striatum	O
+.	O
+
+Nevertheless	O
+,	O
+there	O
+occurs	O
+some	O
+real	O
+tolerance	O
+to	O
+this	O
+effect	O
+.	O
+
+The	O
+rapid	O
+alternations	O
+of	O
+rigidity	B-Disease
+and	O
+the	O
+signs	O
+of	O
+dopaminergic	O
+activation	O
+observed	O
+in	O
+the	O
+animals	O
+of	O
+the	O
+AS	O
+/	O
+KS	O
+group	O
+might	O
+be	O
+due	O
+to	O
+rapid	O
+shifts	O
+in	O
+the	O
+predominance	O
+of	O
+various	O
+DA	O
+-	O
+innervated	O
+structures	O
+.	O
+
+A	O
+case	O
+of	O
+massive	O
+rhabdomyolysis	B-Disease
+following	O
+molindone	B-Chemical
+administration	O
+.	O
+
+Rhabdomyolysis	B-Disease
+is	O
+a	O
+potentially	O
+lethal	O
+syndrome	O
+that	O
+psychiatric	B-Disease
+patients	O
+seem	O
+predisposed	O
+to	O
+develop	O
+.	O
+
+The	O
+clinical	O
+signs	O
+and	O
+symptoms	O
+,	O
+typical	O
+laboratory	O
+features	O
+,	O
+and	O
+complications	O
+of	O
+rhabdomyolysis	B-Disease
+are	O
+presented	O
+.	O
+
+The	O
+case	O
+of	O
+a	O
+schizophrenic	B-Disease
+patient	O
+is	O
+reported	O
+to	O
+illustrate	O
+massive	O
+rhabdomyolysis	B-Disease
+and	O
+subsequent	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+following	O
+molindone	B-Chemical
+administration	O
+.	O
+
+Physicians	O
+who	O
+prescribe	O
+molindone	B-Chemical
+should	O
+be	O
+aware	O
+of	O
+this	O
+reaction	O
+.	O
+
+Compression	B-Disease
+neuropathy	I-Disease
+of	I-Disease
+the	I-Disease
+radial	I-Disease
+nerve	I-Disease
+due	O
+to	O
+pentazocine	B-Chemical
+-	O
+induced	O
+fibrous	B-Disease
+myopathy	I-Disease
+.	O
+
+Fibrous	B-Disease
+myopathy	I-Disease
+is	O
+a	O
+common	O
+,	O
+well	O
+-	O
+known	O
+side	O
+effect	O
+of	O
+repeated	O
+pentazocine	B-Chemical
+injection	O
+.	O
+
+However	O
+,	O
+compression	B-Disease
+neuropathy	I-Disease
+due	O
+to	O
+fibrotic	O
+muscle	O
+affected	O
+by	O
+pentazocine	B-Chemical
+-	O
+induced	O
+myopathy	B-Disease
+has	O
+not	O
+previously	O
+been	O
+reported	O
+.	O
+
+In	O
+a	O
+37	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+documented	O
+pentazocine	B-Chemical
+-	O
+induced	O
+fibrous	B-Disease
+myopathy	I-Disease
+of	O
+triceps	O
+and	O
+deltoid	O
+muscles	O
+bilaterally	O
+and	O
+a	O
+three	O
+-	O
+week	O
+history	O
+of	O
+right	O
+wrist	O
+drop	O
+,	O
+electrodiagnostic	O
+examination	O
+showed	O
+a	O
+severe	O
+but	O
+partial	O
+lesion	O
+of	O
+the	O
+right	O
+radial	O
+nerve	O
+distal	O
+to	O
+the	O
+branches	O
+to	O
+the	O
+triceps	O
+,	O
+in	O
+addition	O
+to	O
+the	O
+fibrous	B-Disease
+myopathy	I-Disease
+.	O
+
+Surgery	O
+revealed	O
+the	O
+right	O
+radial	O
+nerve	O
+to	O
+be	O
+severely	O
+compressed	O
+by	O
+the	O
+densely	O
+fibrotic	O
+lateral	O
+head	O
+of	O
+the	O
+triceps	O
+.	O
+
+Decompression	O
+and	O
+neurolysis	O
+were	O
+performed	O
+with	O
+good	O
+subsequent	O
+recovery	O
+of	O
+function	O
+.	O
+
+Recurrent	O
+reversible	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+from	O
+amphotericin	B-Chemical
+.	O
+
+A	O
+patient	O
+with	O
+cryptogenic	O
+cirrhosis	B-Disease
+and	O
+disseminated	O
+sporotrichosis	B-Disease
+developed	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+immediately	O
+following	O
+the	O
+administration	O
+of	O
+amphotericin	B-Chemical
+B	I-Chemical
+on	O
+four	O
+separate	O
+occasions	O
+.	O
+
+The	O
+abruptness	O
+of	O
+the	O
+renal	B-Disease
+failure	I-Disease
+and	O
+its	O
+reversibility	O
+within	O
+days	O
+suggests	O
+that	O
+there	O
+was	O
+a	O
+functional	O
+component	O
+to	O
+the	O
+renal	B-Disease
+dysfunction	I-Disease
+.	O
+
+We	O
+propose	O
+that	O
+amphotericin	B-Chemical
+,	O
+in	O
+the	O
+setting	O
+of	O
+reduced	O
+effective	O
+arterial	O
+volume	O
+,	O
+may	O
+activate	O
+tubuloglomerular	O
+feedback	O
+,	O
+thereby	O
+contributing	O
+to	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+.	O
+
+Cerebral	B-Disease
+infarction	I-Disease
+with	O
+a	O
+single	O
+oral	O
+dose	O
+of	O
+phenylpropanolamine	B-Chemical
+.	O
+
+Phenylpropanolamine	B-Chemical
+(	O
+PPA	B-Chemical
+)	O
+,	O
+a	O
+synthetic	O
+sympathomimetic	O
+that	O
+is	O
+structurally	O
+similar	O
+to	O
+amphetamine	B-Chemical
+,	O
+is	O
+available	O
+over	O
+the	O
+counter	O
+in	O
+anorectics	O
+,	O
+nasal	O
+congestants	O
+,	O
+and	O
+cold	O
+preparations	O
+.	O
+
+Its	O
+prolonged	O
+use	O
+or	O
+overuse	O
+has	O
+been	O
+associated	O
+with	O
+seizures	B-Disease
+,	O
+intracerebral	B-Disease
+hemorrhage	I-Disease
+,	O
+neuropsychiatric	B-Disease
+symptoms	I-Disease
+,	O
+and	O
+nonhemorrhagic	O
+cerebral	B-Disease
+infarction	I-Disease
+.	O
+
+We	O
+report	O
+the	O
+case	O
+of	O
+a	O
+young	O
+woman	O
+who	O
+suffered	O
+a	O
+cerebral	B-Disease
+infarction	I-Disease
+after	O
+taking	O
+a	O
+single	O
+oral	O
+dose	O
+of	O
+PPA	B-Chemical
+.	O
+
+Remission	O
+induction	O
+of	O
+meningeal	B-Disease
+leukemia	I-Disease
+with	O
+high	O
+-	O
+dose	O
+intravenous	O
+methotrexate	B-Chemical
+.	O
+
+Twenty	O
+children	O
+with	O
+acute	B-Disease
+lymphoblastic	I-Disease
+leukemia	I-Disease
+who	O
+developed	O
+meningeal	B-Disease
+disease	I-Disease
+were	O
+treated	O
+with	O
+a	O
+high	O
+-	O
+dose	O
+intravenous	O
+methotrexate	B-Chemical
+regimen	O
+that	O
+was	O
+designed	O
+to	O
+achieve	O
+and	O
+maintain	O
+CSF	O
+methotrexate	B-Chemical
+concentrations	O
+of	O
+10	O
+(	O
+-	O
+5	O
+)	O
+mol	O
+/	O
+L	O
+without	O
+the	O
+need	O
+for	O
+concomitant	O
+intrathecal	O
+dosing	O
+.	O
+
+The	O
+methotrexate	B-Chemical
+was	O
+administered	O
+as	O
+a	O
+loading	O
+dose	O
+of	O
+6	O
+,	O
+000	O
+mg	O
+/	O
+m2	O
+for	O
+a	O
+period	O
+of	O
+one	O
+hour	O
+followed	O
+by	O
+an	O
+infusion	O
+of	O
+1	O
+,	O
+200	O
+mg	O
+/	O
+m2	O
+/	O
+h	O
+for	O
+23	O
+hours	O
+.	O
+
+Leucovorin	B-Chemical
+rescue	O
+was	O
+initiated	O
+12	O
+hours	O
+after	O
+the	O
+end	O
+of	O
+the	O
+infusion	O
+with	O
+a	O
+loading	O
+dose	O
+of	O
+200	O
+mg	O
+/	O
+m2	O
+followed	O
+by	O
+12	O
+mg	O
+/	O
+m2	O
+every	O
+three	O
+hours	O
+for	O
+six	O
+doses	O
+and	O
+then	O
+every	O
+six	O
+hours	O
+until	O
+the	O
+plasma	O
+methotrexate	B-Chemical
+level	O
+decreased	O
+to	O
+less	O
+than	O
+1	O
+X	O
+10	O
+(	O
+-	O
+7	O
+)	O
+mol	O
+/	O
+L	O
+.	O
+
+The	O
+mean	O
+steady	O
+-	O
+state	O
+plasma	O
+and	O
+CSF	O
+methotrexate	B-Chemical
+concentrations	O
+achieved	O
+were	O
+1	O
+.	O
+1	O
+X	O
+10	O
+(	O
+-	O
+3	O
+)	O
+mol	O
+/	O
+L	O
+and	O
+3	O
+.	O
+6	O
+X	O
+10	O
+(	O
+-	O
+5	O
+)	O
+mol	O
+/	O
+L	O
+,	O
+respectively	O
+.	O
+
+All	O
+20	O
+patients	O
+responded	O
+to	O
+this	O
+regimen	O
+,	O
+16	O
+/	O
+20	O
+(	O
+80	O
+%	O
+)	O
+achieved	O
+a	O
+complete	O
+remission	O
+,	O
+and	O
+20	O
+%	O
+obtained	O
+a	O
+partial	O
+remission	O
+.	O
+
+The	O
+most	O
+common	O
+toxicities	B-Disease
+encountered	O
+were	O
+transient	O
+serum	O
+transaminase	O
+and	O
+bilirubin	B-Chemical
+elevations	O
+,	O
+neutropenia	B-Disease
+,	O
+and	O
+mucositis	B-Disease
+.	O
+
+One	O
+patient	O
+had	O
+focal	O
+seizures	B-Disease
+and	O
+transient	B-Disease
+hemiparesis	I-Disease
+but	O
+recovered	O
+completely	O
+.	O
+
+High	O
+-	O
+dose	O
+intravenous	O
+methotrexate	B-Chemical
+is	O
+an	O
+effective	O
+treatment	O
+for	O
+the	O
+induction	O
+of	O
+remission	O
+after	O
+meningeal	O
+relapse	O
+in	O
+acute	B-Disease
+lymphoblastic	I-Disease
+leukemia	I-Disease
+.	O
+
+Interaction	O
+of	O
+cyclosporin	B-Chemical
+A	I-Chemical
+with	O
+antineoplastic	O
+agents	O
+.	O
+
+A	O
+synergistic	O
+effect	O
+of	O
+etoposide	B-Chemical
+and	O
+cyclosporin	B-Chemical
+A	I-Chemical
+was	O
+observed	O
+in	O
+a	O
+patient	O
+with	O
+acute	B-Disease
+T	I-Disease
+-	I-Disease
+lymphocytic	I-Disease
+leukemia	I-Disease
+in	O
+relapse	O
+.	O
+
+The	O
+concomitant	O
+administration	O
+of	O
+etoposide	B-Chemical
+and	O
+cyclosporin	B-Chemical
+A	I-Chemical
+resulted	O
+in	O
+eradication	O
+of	O
+hitherto	O
+refractory	O
+leukemic	B-Disease
+infiltration	I-Disease
+of	O
+bone	O
+marrow	O
+.	O
+
+Severe	O
+side	O
+effects	O
+in	O
+terms	O
+of	O
+mental	O
+confusion	B-Disease
+and	O
+progressive	O
+hyperbilirubinemia	B-Disease
+,	O
+however	O
+,	O
+point	O
+to	O
+an	O
+enhancement	O
+not	O
+only	O
+of	O
+antineoplastic	O
+effects	O
+but	O
+also	O
+of	O
+toxicity	B-Disease
+in	O
+normal	O
+tissues	O
+.	O
+
+This	O
+report	O
+demonstrates	O
+for	O
+the	O
+first	O
+time	O
+that	O
+the	O
+pharmacodynamic	O
+properties	O
+of	O
+cyclosporin	B-Chemical
+A	I-Chemical
+may	O
+not	O
+be	O
+confined	O
+strictly	O
+to	O
+suppression	O
+of	O
+normal	O
+T	O
+-	O
+cell	O
+functions	O
+.	O
+
+Incidence	O
+of	O
+neoplasms	B-Disease
+in	O
+patients	O
+with	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+exposed	O
+to	O
+different	O
+treatment	O
+regimens	O
+.	O
+
+Immunosuppressive	O
+drugs	O
+have	O
+been	O
+used	O
+during	O
+the	O
+last	O
+30	O
+years	O
+in	O
+treatment	O
+of	O
+patients	O
+with	O
+severe	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+.	O
+
+The	O
+drugs	O
+commonly	O
+used	O
+are	O
+cyclophosphamide	B-Chemical
+and	O
+chlorambucil	B-Chemical
+(	O
+alkylating	B-Chemical
+agents	I-Chemical
+)	O
+,	O
+azathioprine	B-Chemical
+(	O
+purine	B-Chemical
+analogue	O
+)	O
+,	O
+and	O
+methotrexate	B-Chemical
+(	O
+folic	B-Chemical
+acid	I-Chemical
+analogue	O
+)	O
+.	O
+
+There	O
+is	O
+evidence	O
+that	O
+all	O
+four	O
+immunosuppressive	O
+drugs	O
+can	O
+reduce	O
+synovitis	B-Disease
+,	O
+but	O
+disease	O
+activity	O
+almost	O
+always	O
+recurs	O
+after	O
+therapy	O
+is	O
+stopped	O
+.	O
+
+Since	O
+adverse	O
+reactions	O
+are	O
+frequent	O
+,	O
+less	O
+than	O
+50	O
+percent	O
+of	O
+patients	O
+are	O
+able	O
+to	O
+continue	O
+a	O
+particular	O
+drug	O
+for	O
+more	O
+than	O
+one	O
+year	O
+.	O
+
+Since	O
+it	O
+takes	O
+three	O
+to	O
+12	O
+months	O
+to	O
+achieve	O
+maximal	O
+effects	O
+,	O
+those	O
+patients	O
+who	O
+are	O
+unable	O
+to	O
+continue	O
+the	O
+drug	O
+receive	O
+little	O
+benefit	O
+from	O
+it	O
+.	O
+
+Patients	O
+treated	O
+with	O
+alkylating	B-Chemical
+agents	I-Chemical
+have	O
+an	O
+increased	O
+risk	O
+of	O
+development	O
+of	O
+acute	B-Disease
+nonlymphocytic	I-Disease
+leukemia	I-Disease
+,	O
+and	O
+both	O
+alkylating	B-Chemical
+agents	I-Chemical
+and	O
+azathioprine	B-Chemical
+are	O
+associated	O
+with	O
+the	O
+development	O
+of	O
+non	B-Disease
+-	I-Disease
+Hodgkin	I-Disease
+'	I-Disease
+s	I-Disease
+lymphoma	I-Disease
+.	O
+
+Cyclophosphamide	B-Chemical
+therapy	O
+increases	O
+the	O
+risk	O
+of	O
+carcinoma	B-Disease
+of	I-Disease
+the	I-Disease
+bladder	I-Disease
+.	O
+
+There	O
+have	O
+been	O
+several	O
+long	O
+-	O
+term	O
+studies	O
+of	O
+patients	O
+with	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+treated	O
+with	O
+azathioprine	B-Chemical
+and	O
+cyclophosphamide	B-Chemical
+and	O
+the	O
+incidence	O
+of	O
+most	O
+of	O
+the	O
+common	O
+cancers	B-Disease
+is	O
+not	O
+increased	O
+.	O
+
+Data	O
+on	O
+the	O
+possible	O
+increased	O
+risk	O
+of	O
+malignancy	B-Disease
+in	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+are	O
+still	O
+being	O
+collected	O
+,	O
+and	O
+until	O
+further	O
+information	O
+is	O
+available	O
+,	O
+the	O
+use	O
+of	O
+immunosuppressive	O
+drugs	O
+,	O
+particularly	O
+alkylating	B-Chemical
+agents	I-Chemical
+,	O
+in	O
+the	O
+treatment	O
+of	O
+rheumatoid	B-Disease
+arthritis	I-Disease
+should	O
+be	O
+reserved	O
+for	O
+patients	O
+with	O
+severe	O
+progressive	O
+disease	O
+or	O
+life	O
+-	O
+threatening	O
+complications	O
+.	O
+
+Warfarin	B-Chemical
+-	O
+induced	O
+iliopsoas	O
+hemorrhage	B-Disease
+with	O
+subsequent	O
+femoral	B-Disease
+nerve	I-Disease
+palsy	I-Disease
+.	O
+
+We	O
+present	O
+the	O
+case	O
+of	O
+a	O
+28	O
+-	O
+year	O
+-	O
+old	O
+man	O
+on	O
+chronic	O
+warfarin	B-Chemical
+therapy	O
+who	O
+sustained	O
+a	O
+minor	O
+muscle	B-Disease
+tear	I-Disease
+and	O
+developed	O
+increasing	O
+pain	B-Disease
+and	O
+a	O
+flexure	O
+contracture	B-Disease
+of	O
+the	O
+right	O
+hip	O
+.	O
+
+Surgical	O
+exploration	O
+revealed	O
+an	O
+iliopsoas	O
+hematoma	B-Disease
+and	O
+femoral	O
+nerve	B-Disease
+entrapment	I-Disease
+,	O
+resulting	O
+in	O
+a	O
+femoral	B-Disease
+nerve	I-Disease
+palsy	I-Disease
+and	O
+partial	B-Disease
+loss	I-Disease
+of	I-Disease
+quadriceps	I-Disease
+functions	I-Disease
+.	O
+
+Anticoagulant	O
+-	O
+induced	O
+femoral	B-Disease
+nerve	I-Disease
+palsy	I-Disease
+represents	O
+the	O
+most	O
+common	O
+form	O
+of	O
+warfarin	B-Chemical
+-	O
+induced	O
+peripheral	B-Disease
+neuropathy	I-Disease
+;	O
+it	O
+is	O
+characterized	O
+by	O
+severe	O
+pain	B-Disease
+in	O
+the	O
+inguinal	O
+region	O
+,	O
+varying	O
+degrees	O
+of	O
+motor	B-Disease
+and	I-Disease
+sensory	I-Disease
+impairment	I-Disease
+,	O
+and	O
+flexure	O
+contracture	B-Disease
+of	O
+the	O
+involved	O
+extremity	O
+.	O
+
+Pneumonitis	O
+with	O
+pleural	B-Disease
+and	I-Disease
+pericardial	I-Disease
+effusion	I-Disease
+and	O
+neuropathy	B-Disease
+during	O
+amiodarone	B-Chemical
+therapy	O
+.	O
+
+A	O
+patient	O
+with	O
+sinuatrial	B-Disease
+disease	I-Disease
+and	O
+implanted	O
+pacemaker	O
+was	O
+treated	O
+with	O
+amiodarone	B-Chemical
+(	O
+maximum	O
+dose	O
+1000	O
+mg	O
+,	O
+maintenance	O
+dose	O
+800	O
+mg	O
+daily	O
+)	O
+for	O
+10	O
+months	O
+,	O
+for	O
+control	O
+of	O
+supraventricular	B-Disease
+tachyarrhythmias	I-Disease
+.	O
+
+He	O
+developed	O
+pneumonitis	B-Disease
+,	O
+pleural	B-Disease
+and	I-Disease
+pericardial	I-Disease
+effusions	I-Disease
+,	O
+and	O
+a	O
+predominantly	O
+proximal	B-Disease
+motor	I-Disease
+neuropathy	I-Disease
+.	O
+
+Immediate	O
+but	O
+gradual	O
+improvement	O
+followed	O
+withdrawal	O
+of	O
+amiodarone	B-Chemical
+and	O
+treatment	O
+with	O
+prednisolone	B-Chemical
+.	O
+
+Review	O
+of	O
+this	O
+and	O
+previously	O
+reported	O
+cases	O
+indicates	O
+the	O
+need	O
+for	O
+early	O
+diagnosis	O
+of	O
+amiodarone	B-Chemical
+pneumonitis	B-Disease
+,	O
+immediate	O
+withdrawal	O
+of	O
+amiodarone	B-Chemical
+,	O
+and	O
+prompt	O
+but	O
+continued	O
+steroid	B-Chemical
+therapy	O
+to	O
+ensure	O
+full	O
+recovery	O
+.	O
+
+Amiodarone	B-Chemical
+-	O
+induced	O
+sinoatrial	B-Disease
+block	I-Disease
+.	O
+
+We	O
+observed	O
+sinoatrial	B-Disease
+block	I-Disease
+due	O
+to	O
+chronic	O
+amiodarone	B-Chemical
+administration	O
+in	O
+a	O
+5	O
+-	O
+year	O
+-	O
+old	O
+boy	O
+with	O
+primary	B-Disease
+cardiomyopathy	I-Disease
+,	O
+Wolff	B-Disease
+-	I-Disease
+Parkinson	I-Disease
+-	I-Disease
+White	I-Disease
+syndrome	I-Disease
+and	O
+supraventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+Reduction	O
+in	O
+the	O
+dosage	O
+of	O
+amiodarone	B-Chemical
+resulted	O
+in	O
+the	O
+disappearance	O
+of	O
+the	O
+sinoatrial	B-Disease
+block	I-Disease
+and	O
+the	O
+persistence	O
+of	O
+asymptomatic	O
+sinus	B-Disease
+bradycardia	I-Disease
+.	O
+
+Desipramine	B-Chemical
+-	O
+induced	O
+delirium	B-Disease
+at	O
+"	O
+subtherapeutic	O
+"	O
+concentrations	O
+:	O
+a	O
+case	O
+report	O
+.	O
+
+An	O
+elderly	O
+patient	O
+treated	O
+with	O
+low	O
+dose	O
+Desipramine	B-Chemical
+developed	O
+a	O
+delirium	B-Disease
+while	O
+her	O
+plasma	O
+level	O
+was	O
+in	O
+the	O
+"	O
+subtherapeutic	O
+"	O
+range	O
+.	O
+
+Delirium	B-Disease
+,	O
+which	O
+may	O
+be	O
+induced	O
+by	O
+tricyclic	O
+drug	O
+therapy	O
+in	O
+the	O
+elderly	O
+,	O
+can	O
+be	O
+caused	O
+by	O
+tricyclics	O
+with	O
+low	O
+anticholinergic	O
+potency	O
+.	O
+
+Therapeutic	O
+ranges	O
+for	O
+antidepressants	B-Chemical
+that	O
+have	O
+been	O
+derived	O
+from	O
+general	O
+adult	O
+population	O
+studies	O
+may	O
+not	O
+be	O
+appropriate	O
+for	O
+the	O
+elderly	O
+.	O
+
+Further	O
+studies	O
+of	O
+specifically	O
+elderly	O
+patients	O
+are	O
+now	O
+required	O
+to	O
+establish	O
+safer	O
+and	O
+more	O
+appropriate	O
+guidelines	O
+for	O
+drug	O
+therapy	O
+.	O
+
+Indomethacin	B-Chemical
+-	O
+induced	O
+renal	B-Disease
+insufficiency	I-Disease
+:	O
+recurrence	O
+on	O
+rechallenge	O
+.	O
+
+We	O
+have	O
+reported	O
+a	O
+case	O
+of	O
+acute	O
+oliguric	O
+renal	B-Disease
+failure	I-Disease
+with	O
+hyperkalemia	B-Disease
+in	O
+a	O
+patient	O
+with	O
+cirrhosis	B-Disease
+,	O
+ascites	B-Disease
+,	O
+and	O
+cor	B-Disease
+pulmonale	I-Disease
+after	O
+indomethacin	B-Chemical
+therapy	O
+.	O
+
+Prompt	O
+restoration	O
+of	O
+renal	O
+function	O
+followed	O
+drug	O
+withdrawal	O
+,	O
+while	O
+re	O
+-	O
+exposure	O
+to	O
+a	O
+single	O
+dose	O
+of	O
+indomethacin	B-Chemical
+caused	O
+recurrence	O
+of	O
+acute	O
+reversible	O
+oliguria	B-Disease
+.	O
+
+Our	O
+case	O
+supports	O
+the	O
+hypothesis	O
+that	O
+endogenous	O
+renal	O
+prostaglandins	B-Chemical
+play	O
+a	O
+role	O
+in	O
+the	O
+maintenance	O
+of	O
+renal	O
+blood	O
+flow	O
+when	O
+circulating	O
+plasma	O
+volume	O
+is	O
+diminished	O
+.	O
+
+Since	O
+nonsteroidal	O
+anti	O
+-	O
+inflammatory	O
+agents	O
+interfere	O
+with	O
+this	O
+compensatory	O
+mechanism	O
+and	O
+may	O
+cause	O
+acute	B-Disease
+renal	I-Disease
+failure	I-Disease
+,	O
+they	O
+should	O
+be	O
+used	O
+with	O
+caution	O
+in	O
+such	O
+patients	O
+.	O
+
+Patterns	O
+of	O
+hepatic	B-Disease
+injury	I-Disease
+induced	O
+by	O
+methyldopa	B-Chemical
+.	O
+
+Twelve	O
+patients	O
+with	O
+liver	B-Disease
+disease	I-Disease
+related	O
+to	O
+methyldopa	B-Chemical
+were	O
+seen	O
+between	O
+1967	O
+and	O
+1977	O
+.	O
+
+Illness	O
+occurred	O
+within	O
+1	O
+-	O
+-	O
+9	O
+weeks	O
+of	O
+commencement	O
+of	O
+therapy	O
+in	O
+9	O
+patients	O
+,	O
+the	O
+remaining	O
+3	O
+patients	O
+having	O
+received	O
+the	O
+drug	O
+for	O
+13	O
+months	O
+,	O
+15	O
+months	O
+and	O
+7	O
+years	O
+before	O
+experiencing	O
+symptoms	O
+.	O
+
+Jaundice	B-Disease
+with	O
+tender	O
+hepatomegaly	B-Disease
+,	O
+usually	O
+preceded	O
+by	O
+symptoms	O
+of	O
+malaise	O
+,	O
+anorexia	B-Disease
+,	O
+nausea	B-Disease
+and	O
+vomiting	B-Disease
+,	O
+and	O
+associated	O
+with	O
+upper	O
+abdominal	B-Disease
+pain	I-Disease
+,	O
+was	O
+an	O
+invariable	O
+finding	O
+in	O
+all	O
+patients	O
+.	O
+
+Biochemical	O
+liver	O
+function	O
+tests	O
+indicated	O
+hepatocellular	O
+necrosis	B-Disease
+and	O
+correlated	O
+with	O
+histopathological	O
+evidence	O
+of	O
+hepatic	B-Disease
+injury	I-Disease
+,	O
+the	O
+spectrum	O
+of	O
+which	O
+ranged	O
+from	O
+fatty	B-Disease
+change	I-Disease
+and	O
+focal	O
+hepatocellular	O
+necrosis	B-Disease
+to	O
+massive	B-Disease
+hepatic	I-Disease
+necrosis	I-Disease
+.	O
+
+Most	O
+patients	O
+showed	O
+moderate	O
+to	O
+severe	O
+acute	B-Disease
+hepatitis	I-Disease
+or	O
+chronic	B-Disease
+active	I-Disease
+hepatitis	I-Disease
+with	O
+associated	O
+cholestasis	B-Disease
+.	O
+
+The	O
+drug	O
+was	O
+withdrawn	O
+on	O
+presentation	O
+to	O
+hospital	O
+in	O
+11	O
+patients	O
+,	O
+with	O
+rapid	O
+clinical	O
+improvement	O
+in	O
+9	O
+.	O
+
+One	O
+patient	O
+died	O
+,	O
+having	O
+presented	O
+in	O
+hepatic	B-Disease
+failure	I-Disease
+,	O
+and	O
+another	O
+,	O
+who	O
+had	O
+been	O
+taking	O
+methyldopa	B-Chemical
+for	O
+7	O
+years	O
+,	O
+showed	O
+slower	O
+clinical	O
+and	O
+biochemical	O
+resolution	O
+over	O
+a	O
+period	O
+of	O
+several	O
+months	O
+.	O
+
+The	O
+remaining	O
+patient	O
+in	O
+the	O
+series	O
+developed	O
+fulminant	B-Disease
+hepatitis	I-Disease
+when	O
+the	O
+drug	O
+was	O
+accidentally	O
+recommenced	O
+1	O
+year	O
+after	O
+a	O
+prior	O
+episode	O
+of	O
+methyldopa	B-Chemical
+-	O
+induced	O
+hepatitis	B-Disease
+.	O
+
+In	O
+this	O
+latter	O
+patient	O
+,	O
+and	O
+in	O
+2	O
+others	O
+,	O
+the	O
+causal	O
+relationship	O
+between	O
+methyldopa	B-Chemical
+and	O
+hepatic	B-Disease
+dysfunction	I-Disease
+was	O
+proved	O
+with	O
+the	O
+recurrence	O
+of	O
+hepatitis	B-Disease
+within	O
+2	O
+weeks	O
+of	O
+re	O
+-	O
+exposure	O
+to	O
+the	O
+drug	O
+.	O
+
+Suxamethonium	B-Chemical
+infusion	O
+rate	O
+and	O
+observed	O
+fasciculations	B-Disease
+.	O
+
+A	O
+dose	O
+-	O
+response	O
+study	O
+.	O
+
+Suxamethonium	B-Chemical
+chloride	I-Chemical
+(	O
+Sch	B-Chemical
+)	O
+was	O
+administered	O
+i	O
+.	O
+v	O
+.	O
+to	O
+36	O
+adult	O
+males	O
+at	O
+six	O
+rates	O
+:	O
+0	O
+.	O
+25	O
+mg	O
+s	O
+-	O
+1	O
+to	O
+20	O
+mg	O
+s	O
+-	O
+1	O
+.	O
+
+The	O
+infusion	O
+was	O
+discontinued	O
+either	O
+when	O
+there	O
+was	O
+no	O
+muscular	O
+response	O
+to	O
+tetanic	B-Disease
+stimulation	O
+of	O
+the	O
+ulnar	O
+nerve	O
+or	O
+when	O
+Sch	B-Chemical
+120	O
+mg	O
+was	O
+exceeded	O
+.	O
+
+Six	O
+additional	O
+patients	O
+received	O
+a	O
+30	O
+-	O
+mg	O
+i	O
+.	O
+v	O
+.	O
+bolus	O
+dose	O
+.	O
+
+Fasciculations	B-Disease
+in	O
+six	O
+areas	O
+of	O
+the	O
+body	O
+were	O
+scored	O
+from	O
+0	O
+to	O
+3	O
+and	O
+summated	O
+as	O
+a	O
+total	O
+fasciculation	B-Disease
+score	O
+.	O
+
+The	O
+times	O
+to	O
+first	O
+fasciculation	B-Disease
+,	O
+twitch	B-Disease
+suppression	O
+and	O
+tetanus	B-Disease
+suppression	O
+were	O
+inversely	O
+related	O
+to	O
+the	O
+infusion	O
+rates	O
+.	O
+
+Fasciculations	B-Disease
+in	O
+the	O
+six	O
+areas	O
+and	O
+the	O
+total	O
+fasciculation	B-Disease
+score	O
+were	O
+related	O
+directly	O
+to	O
+the	O
+rate	O
+of	O
+infusion	O
+.	O
+
+Total	O
+fasciculation	B-Disease
+scores	O
+in	O
+the	O
+30	O
+-	O
+mg	O
+bolus	O
+group	O
+and	O
+the	O
+5	O
+-	O
+mg	O
+s	O
+-	O
+1	O
+and	O
+20	O
+-	O
+mg	O
+s	O
+-	O
+1	O
+infusion	O
+groups	O
+were	O
+not	O
+significantly	O
+different	O
+.	O
+
+Treatment	O
+of	O
+psoriasis	B-Disease
+with	O
+azathioprine	B-Chemical
+.	O
+
+Azathioprine	B-Chemical
+treatment	O
+benefited	O
+19	O
+(	O
+66	O
+%	O
+)	O
+out	O
+of	O
+29	O
+patients	O
+suffering	O
+from	O
+severe	O
+psoriasis	B-Disease
+.	O
+
+Haematological	O
+complications	O
+were	O
+not	O
+troublesome	O
+and	O
+results	O
+of	O
+biochemical	O
+liver	O
+function	O
+tests	O
+remained	O
+normal	O
+.	O
+
+Minimal	O
+cholestasis	B-Disease
+was	O
+seen	O
+in	O
+two	O
+cases	O
+and	O
+portal	O
+fibrosis	B-Disease
+of	O
+a	O
+reversible	O
+degree	O
+in	O
+eight	O
+.	O
+
+Liver	O
+biopsies	O
+should	O
+be	O
+undertaken	O
+at	O
+regular	O
+intervals	O
+if	O
+azathioprine	B-Chemical
+therapy	O
+is	O
+continued	O
+so	O
+that	O
+structural	O
+liver	B-Disease
+damage	I-Disease
+may	O
+be	O
+detected	O
+at	O
+an	O
+early	O
+and	O
+reversible	O
+stage	O
+.	O
+
+Angiosarcoma	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+associated	O
+with	O
+diethylstilbestrol	B-Chemical
+.	O
+
+Angiosarcoma	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+occurred	O
+in	O
+a	O
+76	O
+-	O
+year	O
+-	O
+old	O
+man	O
+who	O
+had	O
+been	O
+treated	O
+for	O
+a	O
+well	O
+-	O
+differentiated	O
+adenocarcinoma	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+with	O
+diethylstilbestrol	B-Chemical
+for	O
+13	O
+years	O
+.	O
+
+Angiosarcoma	B-Disease
+was	O
+also	O
+present	O
+within	O
+pulmonary	O
+and	O
+renal	O
+arteries	O
+.	O
+
+The	O
+possibility	O
+that	O
+the	O
+intraarterial	B-Disease
+lesions	I-Disease
+might	O
+represent	O
+independent	O
+primary	O
+tumors	B-Disease
+is	O
+considered	O
+.	O
+
+Galanthamine	B-Chemical
+hydrobromide	I-Chemical
+,	O
+a	O
+longer	O
+acting	O
+anticholinesterase	O
+drug	O
+,	O
+in	O
+the	O
+treatment	O
+of	O
+the	O
+central	O
+effects	O
+of	O
+scopolamine	B-Chemical
+(	O
+Hyoscine	B-Chemical
+)	O
+.	O
+
+Galanthamine	B-Chemical
+hydrobromide	I-Chemical
+,	O
+an	O
+anticholinesterase	O
+drug	O
+capable	O
+of	O
+penetrating	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+,	O
+was	O
+used	O
+in	O
+a	O
+patient	O
+demonstrating	O
+central	O
+effects	O
+of	O
+scopolamine	B-Chemical
+(	O
+hyoscine	B-Chemical
+)	O
+overdosage	B-Disease
+.	O
+
+It	O
+is	O
+longer	O
+acting	O
+than	O
+physostigmine	B-Chemical
+and	O
+is	O
+used	O
+in	O
+anaesthesia	O
+to	O
+reverse	O
+the	O
+non	O
+-	O
+depolarizing	O
+neuromuscular	O
+block	O
+.	O
+
+However	O
+,	O
+studies	O
+into	O
+the	O
+dose	O
+necessary	O
+to	O
+combating	O
+scopolamine	B-Chemical
+intoxication	O
+are	O
+indicated	O
+.	O
+
+Comparison	O
+of	O
+the	O
+subjective	O
+effects	O
+and	O
+plasma	O
+concentrations	O
+following	O
+oral	O
+and	O
+i	O
+.	O
+m	O
+.	O
+administration	O
+of	O
+flunitrazepam	B-Chemical
+in	O
+volunteers	O
+.	O
+
+Flunitrazepam	B-Chemical
+0	O
+.	O
+5	O
+,	O
+1	O
+.	O
+0	O
+or	O
+2	O
+.	O
+0	O
+mg	O
+was	O
+given	O
+by	O
+the	O
+oral	O
+or	O
+i	O
+.	O
+m	O
+.	O
+routes	O
+to	O
+groups	O
+of	O
+volunteers	O
+and	O
+its	O
+effects	O
+compared	O
+.	O
+
+Plasma	O
+concentrations	O
+of	O
+the	O
+drug	O
+were	O
+estimated	O
+by	O
+gas	O
+-	O
+liquid	O
+chromatography	O
+,	O
+in	O
+a	O
+smaller	O
+number	O
+of	O
+the	O
+subjects	O
+.	O
+
+The	O
+most	O
+striking	O
+effect	O
+was	O
+sedation	O
+which	O
+increased	O
+with	O
+the	O
+dose	O
+,	O
+2	O
+mg	O
+producing	O
+deep	O
+sleep	O
+although	O
+the	O
+subjects	O
+could	O
+still	O
+be	O
+aroused	O
+.	O
+
+The	O
+effects	O
+of	O
+i	O
+.	O
+m	O
+.	O
+administration	O
+were	O
+apparent	O
+earlier	O
+and	O
+sometimes	O
+lasted	O
+longer	O
+than	O
+those	O
+following	O
+oral	O
+administration	O
+.	O
+
+Dizziness	B-Disease
+was	O
+less	O
+marked	O
+than	O
+sedation	O
+,	O
+but	O
+increased	O
+with	O
+the	O
+dose	O
+.	O
+
+There	O
+was	O
+pain	B-Disease
+on	O
+i	O
+.	O
+m	O
+.	O
+injection	O
+of	O
+flunitrazepam	B-Chemical
+significantly	O
+more	O
+often	O
+than	O
+with	O
+isotonic	O
+saline	O
+.	O
+
+Plasma	O
+concentrations	O
+varied	O
+with	O
+dose	O
+and	O
+route	O
+and	O
+corresponded	O
+qualitatively	O
+with	O
+the	O
+subjective	O
+effects	O
+.	O
+
+The	O
+drug	O
+was	O
+still	O
+present	O
+in	O
+measurable	O
+quantities	O
+after	O
+24	O
+h	O
+even	O
+with	O
+the	O
+smallest	O
+dose	O
+.	O
+
+Possible	O
+teratogenicity	O
+of	O
+sulphasalazine	B-Chemical
+.	O
+
+Three	O
+infants	O
+,	O
+born	O
+of	O
+two	O
+mothers	O
+with	O
+inflammatory	B-Disease
+bowel	I-Disease
+disease	I-Disease
+who	O
+received	O
+treatment	O
+with	O
+sulphasalazine	B-Chemical
+throughout	O
+pregnancy	O
+,	O
+were	O
+found	O
+to	O
+have	O
+major	O
+congenital	B-Disease
+anomalies	I-Disease
+.	O
+
+In	O
+the	O
+singleton	O
+pregnancy	O
+,	O
+the	O
+mother	O
+had	O
+ulcerative	B-Disease
+colitis	I-Disease
+,	O
+and	O
+the	O
+infant	O
+,	O
+a	O
+male	O
+,	O
+had	O
+coarctation	B-Disease
+of	I-Disease
+the	I-Disease
+aorta	I-Disease
+and	O
+a	O
+ventricular	B-Disease
+septal	I-Disease
+defect	I-Disease
+.	O
+
+In	O
+the	O
+twin	O
+pregnancy	O
+,	O
+the	O
+mother	O
+had	O
+Crohn	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+The	O
+first	O
+twin	O
+,	O
+a	O
+female	O
+,	O
+had	O
+a	O
+left	O
+Potter	B-Disease
+-	I-Disease
+type	I-Disease
+IIa	I-Disease
+polycystic	I-Disease
+kidney	I-Disease
+and	O
+a	O
+rudimentary	B-Disease
+left	I-Disease
+uterine	I-Disease
+cornu	I-Disease
+.	O
+
+The	O
+second	O
+twin	O
+,	O
+a	O
+male	O
+,	O
+had	O
+some	O
+features	O
+of	O
+Potter	B-Disease
+'	I-Disease
+s	I-Disease
+facies	I-Disease
+,	O
+hypoplastic	B-Disease
+lungs	I-Disease
+,	O
+absent	B-Disease
+kidneys	I-Disease
+and	I-Disease
+ureters	I-Disease
+,	O
+and	O
+talipes	B-Disease
+equinovarus	I-Disease
+.	O
+
+Despite	O
+reports	O
+to	O
+the	O
+contrary	O
+,	O
+it	O
+is	O
+suggested	O
+that	O
+sulphasalazine	B-Chemical
+may	O
+be	O
+teratogenic	O
+.	O
+
+Thrombotic	B-Disease
+microangiopathy	I-Disease
+and	O
+renal	B-Disease
+failure	I-Disease
+associated	O
+with	O
+antineoplastic	O
+chemotherapy	O
+.	O
+
+Five	O
+patients	O
+with	O
+carcinoma	B-Disease
+developed	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+(	O
+characterized	O
+by	O
+renal	B-Disease
+insufficiency	I-Disease
+,	O
+microangiopathic	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+,	O
+and	O
+usually	O
+thrombocytopenia	B-Disease
+)	O
+after	O
+treatment	O
+with	O
+cisplatin	B-Chemical
+,	O
+bleomycin	B-Chemical
+,	O
+and	O
+a	O
+vinca	B-Chemical
+alkaloid	I-Chemical
+.	O
+
+One	O
+patient	O
+had	O
+thrombotic	B-Disease
+thrombocytopenic	I-Disease
+purpura	I-Disease
+,	O
+three	O
+the	O
+hemolytic	B-Disease
+-	I-Disease
+uremic	I-Disease
+syndrome	I-Disease
+,	O
+and	O
+one	O
+an	O
+apparent	O
+forme	O
+fruste	O
+of	O
+one	O
+of	O
+these	O
+disorders	O
+.	O
+
+Histologic	O
+examination	O
+of	O
+the	O
+renal	O
+tissue	O
+showed	O
+evidence	O
+of	O
+intravascular	B-Disease
+coagulation	I-Disease
+,	O
+primarily	O
+affecting	O
+the	O
+small	O
+arteries	O
+,	O
+arterioles	O
+,	O
+and	O
+glomeruli	O
+.	O
+
+Because	O
+each	O
+patient	O
+was	O
+tumor	B-Disease
+-	O
+free	O
+or	O
+had	O
+only	O
+a	O
+small	O
+tumor	B-Disease
+at	O
+the	O
+onset	O
+of	O
+this	O
+syndrome	O
+,	O
+the	O
+thrombotic	B-Disease
+microangiopathy	I-Disease
+may	O
+have	O
+been	O
+induced	O
+by	O
+chemotherapy	O
+.	O
+
+Diagnosis	O
+of	O
+this	O
+potentially	O
+fatal	O
+complication	O
+may	O
+be	O
+delayed	O
+or	O
+missed	O
+if	O
+renal	O
+tissue	O
+or	O
+the	O
+peripheral	O
+blood	O
+smear	O
+is	O
+not	O
+examined	O
+,	O
+because	O
+renal	B-Disease
+failure	I-Disease
+may	O
+be	O
+ascribed	O
+to	O
+cisplatin	B-Chemical
+nephrotoxicity	B-Disease
+and	O
+the	O
+anemia	B-Disease
+and	O
+thrombocytopenia	B-Disease
+to	O
+drug	O
+-	O
+induced	O
+bone	B-Disease
+marrow	I-Disease
+suppression	I-Disease
+.	O
+
+International	O
+mexiletine	B-Chemical
+and	O
+placebo	O
+antiarrhythmic	O
+coronary	O
+trial	O
+:	O
+I	O
+.	O
+
+Report	O
+on	O
+arrhythmia	B-Disease
+and	O
+other	O
+findings	O
+.	O
+
+Impact	O
+Research	O
+Group	O
+.	O
+
+The	O
+antiarrhythmic	O
+effects	O
+of	O
+the	O
+sustained	O
+release	O
+form	O
+of	O
+mexiletine	B-Chemical
+(	O
+Mexitil	B-Chemical
+-	I-Chemical
+Perlongets	I-Chemical
+)	O
+were	O
+evaluated	O
+in	O
+a	O
+double	O
+-	O
+blind	O
+placebo	O
+trial	O
+in	O
+630	O
+patients	O
+with	O
+recent	O
+documented	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+The	O
+primary	O
+response	O
+variable	O
+was	O
+based	O
+on	O
+central	O
+reading	O
+of	O
+24	O
+hour	O
+ambulatory	O
+electrocardiographic	O
+recordings	O
+and	O
+was	O
+defined	O
+as	O
+the	O
+occurrence	O
+of	O
+30	O
+or	O
+more	O
+single	O
+premature	O
+ventricular	O
+complexes	O
+in	O
+any	O
+two	O
+consecutive	O
+30	O
+minute	O
+blocks	O
+or	O
+one	O
+or	O
+more	O
+runs	O
+of	O
+two	O
+or	O
+more	O
+premature	O
+ventricular	O
+complexes	O
+in	O
+the	O
+entire	O
+24	O
+hour	O
+electrocardiographic	O
+recording	O
+.	O
+
+Large	O
+differences	O
+,	O
+regarded	O
+as	O
+statistically	O
+significant	O
+,	O
+between	O
+the	O
+mexiletine	B-Chemical
+and	O
+placebo	O
+groups	O
+were	O
+noted	O
+in	O
+that	O
+end	O
+point	O
+at	O
+months	O
+1	O
+and	O
+4	O
+,	O
+but	O
+only	O
+trends	O
+were	O
+observed	O
+at	O
+month	O
+12	O
+.	O
+
+These	O
+differences	O
+were	O
+observed	O
+even	O
+though	O
+the	O
+serum	O
+mexiletine	B-Chemical
+levels	O
+obtained	O
+in	O
+this	O
+study	O
+were	O
+generally	O
+lower	O
+than	O
+those	O
+observed	O
+in	O
+studies	O
+that	O
+have	O
+used	O
+the	O
+regular	O
+form	O
+of	O
+the	O
+drug	O
+.	O
+
+There	O
+were	O
+more	O
+deaths	B-Disease
+in	O
+the	O
+mexiletine	B-Chemical
+group	O
+(	O
+7	O
+.	O
+6	O
+%	O
+)	O
+than	O
+in	O
+the	O
+placebo	O
+group	O
+(	O
+4	O
+.	O
+8	O
+%	O
+)	O
+;	O
+the	O
+difference	O
+was	O
+not	O
+statistically	O
+significant	O
+.	O
+
+The	O
+incidence	O
+of	O
+coronary	O
+events	O
+was	O
+similar	O
+in	O
+both	O
+groups	O
+.	O
+
+Previously	O
+recognized	O
+side	O
+effects	O
+,	O
+particularly	O
+tremor	B-Disease
+and	O
+gastrointestinal	B-Disease
+problems	I-Disease
+,	O
+were	O
+more	O
+frequent	O
+in	O
+the	O
+mexiletine	B-Chemical
+group	O
+than	O
+in	O
+the	O
+placebo	O
+group	O
+.	O
+
+Changes	O
+in	O
+heart	O
+size	O
+during	O
+long	O
+-	O
+term	O
+timolol	B-Chemical
+treatment	O
+after	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+The	O
+effect	O
+of	O
+long	O
+-	O
+term	O
+timolol	B-Chemical
+treatment	O
+on	O
+heart	O
+size	O
+after	O
+myocardial	B-Disease
+infarction	I-Disease
+was	O
+evaluated	O
+by	O
+X	O
+-	O
+ray	O
+in	O
+a	O
+double	O
+-	O
+blind	O
+study	O
+including	O
+241	O
+patients	O
+(	O
+placebo	O
+126	O
+,	O
+timolol	B-Chemical
+115	O
+)	O
+.	O
+
+The	O
+follow	O
+-	O
+up	O
+period	O
+was	O
+12	O
+months	O
+.	O
+
+The	O
+timolol	B-Chemical
+-	O
+treated	O
+patients	O
+showed	O
+a	O
+small	O
+but	O
+significant	O
+increase	O
+in	O
+heart	O
+size	O
+from	O
+baseline	O
+in	O
+contrast	O
+to	O
+a	O
+decrease	O
+in	O
+the	O
+placebo	O
+group	O
+.	O
+
+These	O
+differences	O
+may	O
+be	O
+caused	O
+by	O
+timolol	B-Chemical
+-	O
+induced	O
+bradycardia	B-Disease
+and	O
+a	O
+compensatory	O
+increase	O
+in	O
+end	O
+-	O
+diastolic	O
+volume	O
+.	O
+
+The	O
+timolol	B-Chemical
+-	O
+related	O
+increase	O
+in	O
+heart	O
+size	O
+was	O
+observed	O
+only	O
+in	O
+patients	O
+with	O
+normal	O
+and	O
+borderline	O
+heart	O
+size	O
+.	O
+
+In	O
+patients	O
+with	O
+cardiomegaly	B-Disease
+,	O
+the	O
+increase	O
+in	O
+heart	O
+size	O
+was	O
+similar	O
+in	O
+both	O
+groups	O
+.	O
+
+After	O
+re	O
+-	O
+infarction	B-Disease
+,	O
+heart	O
+size	O
+increased	O
+in	O
+the	O
+placebo	O
+group	O
+and	O
+remained	O
+unchanged	O
+in	O
+the	O
+timolol	B-Chemical
+group	O
+.	O
+
+Vitamin	B-Chemical
+D3	I-Chemical
+toxicity	B-Disease
+in	O
+dairy	O
+cows	O
+.	O
+
+Large	O
+parenteral	O
+doses	O
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+(	O
+15	O
+to	O
+17	O
+.	O
+5	O
+x	O
+10	O
+(	O
+6	O
+)	O
+IU	O
+vitamin	B-Chemical
+D3	I-Chemical
+)	O
+were	O
+associated	O
+with	O
+prolonged	O
+hypercalcemia	B-Disease
+,	O
+hyperphosphatemia	B-Disease
+,	O
+and	O
+large	O
+increases	O
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+and	O
+its	O
+metabolites	O
+in	O
+the	O
+blood	O
+plasma	O
+of	O
+nonlactating	O
+nonpregnant	O
+and	O
+pregnant	O
+Jersey	O
+cows	O
+.	O
+
+Calcium	B-Chemical
+concentrations	O
+1	O
+day	O
+postpartum	O
+were	O
+higher	O
+in	O
+cows	O
+treated	O
+with	O
+vitamin	B-Chemical
+D3	I-Chemical
+about	O
+32	O
+days	O
+prepartum	O
+(	O
+8	O
+.	O
+8	O
+mg	O
+/	O
+100	O
+ml	O
+)	O
+than	O
+in	O
+control	O
+cows	O
+(	O
+5	O
+.	O
+5	O
+mg	O
+/	O
+100	O
+ml	O
+)	O
+.	O
+
+None	O
+of	O
+the	O
+cows	O
+treated	O
+with	O
+vitamin	B-Chemical
+D3	I-Chemical
+showed	O
+signs	O
+of	O
+milk	B-Disease
+fever	I-Disease
+during	O
+the	O
+peripartal	O
+period	O
+;	O
+however	O
+,	O
+22	O
+%	O
+of	O
+the	O
+control	O
+cows	O
+developed	O
+clinical	O
+signs	O
+of	O
+milk	B-Disease
+fever	I-Disease
+during	O
+this	O
+period	O
+.	O
+
+Signs	O
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+toxicity	B-Disease
+were	O
+not	O
+observed	O
+in	O
+nonlactating	O
+nonpregnant	O
+cows	O
+;	O
+however	O
+,	O
+pregnant	O
+cows	O
+commonly	O
+developed	O
+severe	O
+signs	O
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+toxicity	B-Disease
+and	O
+10	O
+of	O
+17	O
+cows	O
+died	O
+.	O
+
+There	O
+was	O
+widespread	O
+metastatic	O
+calcification	O
+in	O
+the	O
+cows	O
+that	O
+died	O
+.	O
+
+Because	O
+of	O
+the	O
+extreme	O
+toxicity	B-Disease
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+in	O
+pregnant	O
+Jersey	O
+cows	O
+and	O
+the	O
+low	O
+margin	O
+of	O
+safety	O
+between	O
+doses	O
+of	O
+vitamin	B-Chemical
+D3	I-Chemical
+that	O
+prevent	O
+milk	B-Disease
+fever	I-Disease
+and	O
+doses	O
+that	O
+induce	O
+milk	B-Disease
+fever	I-Disease
+,	O
+we	O
+concluded	O
+that	O
+vitamin	B-Chemical
+D3	I-Chemical
+cannot	O
+be	O
+used	O
+practically	O
+to	O
+prevent	O
+milk	B-Disease
+fever	I-Disease
+when	O
+injected	O
+several	O
+weeks	O
+prepartum	O
+.	O
+
+Diseases	B-Disease
+of	I-Disease
+peripheral	I-Disease
+nerves	I-Disease
+as	O
+seen	O
+in	O
+the	O
+Nigerian	O
+African	O
+.	O
+
+The	O
+anatomical	O
+and	O
+aetiological	O
+diagnoses	O
+of	O
+peripheral	B-Disease
+nerve	I-Disease
+disease	I-Disease
+excluding	O
+its	O
+primary	O
+benign	O
+and	O
+malignant	O
+disorders	O
+,	O
+as	O
+seen	O
+in	O
+358	O
+Nigerians	O
+are	O
+presented	O
+.	O
+
+There	O
+is	O
+a	O
+male	O
+preponderance	O
+and	O
+the	O
+peak	O
+incidence	O
+is	O
+in	O
+the	O
+fourth	O
+decade	O
+.	O
+
+Sensori	B-Disease
+-	I-Disease
+motor	I-Disease
+neuropathy	I-Disease
+was	O
+the	O
+commonest	O
+presentation	O
+(	O
+50	O
+%	O
+)	O
+.	O
+
+Guillain	B-Disease
+-	I-Disease
+Barr	I-Disease
+syndrome	I-Disease
+was	O
+the	O
+commonest	O
+identifiable	O
+cause	O
+(	O
+15	O
+.	O
+6	O
+%	O
+)	O
+,	O
+accounting	O
+for	O
+half	O
+of	O
+the	O
+cases	O
+with	O
+motor	B-Disease
+neuropathy	I-Disease
+.	O
+
+Peripheral	B-Disease
+neuropathy	I-Disease
+due	O
+to	O
+nutritional	B-Disease
+deficiency	I-Disease
+of	O
+thiamine	B-Chemical
+and	O
+riboflavin	B-Chemical
+was	O
+common	O
+(	O
+10	O
+.	O
+1	O
+%	O
+)	O
+and	O
+presented	O
+mainly	O
+as	O
+sensory	O
+and	O
+sensori	B-Disease
+-	I-Disease
+motor	I-Disease
+neuropathy	I-Disease
+.	O
+
+Diabetes	B-Disease
+mellitus	I-Disease
+was	O
+the	O
+major	O
+cause	O
+of	O
+autonomic	B-Disease
+neuropathy	I-Disease
+.	O
+
+Isoniazid	B-Chemical
+was	O
+the	O
+most	O
+frequent	O
+agent	O
+in	O
+drug	O
+-	O
+induced	O
+neuropathy	B-Disease
+.	O
+
+Migraine	B-Disease
+(	O
+20	O
+%	O
+)	O
+was	O
+not	O
+an	O
+uncommon	O
+cause	O
+of	O
+cranial	B-Disease
+neuropathy	I-Disease
+although	O
+malignancies	B-Disease
+arising	O
+from	O
+the	O
+reticuloendothelial	O
+system	O
+or	O
+related	O
+structures	O
+of	O
+the	O
+head	O
+and	O
+neck	O
+were	O
+more	O
+frequent	O
+(	O
+26	O
+%	O
+)	O
+.	O
+
+In	O
+26	O
+.	O
+5	O
+%	O
+of	O
+all	O
+the	O
+cases	O
+,	O
+the	O
+aetiology	O
+of	O
+the	O
+neuropathy	B-Disease
+was	O
+undetermined	O
+.	O
+
+Heredofamilial	O
+and	O
+connective	B-Disease
+tissue	I-Disease
+disorders	I-Disease
+were	O
+rare	O
+.	O
+
+Some	O
+of	O
+the	O
+factors	O
+related	O
+to	O
+the	O
+clinical	O
+presentation	O
+and	O
+pathogenesis	O
+of	O
+the	O
+neuropathies	B-Disease
+are	O
+briefly	O
+discussed	O
+.	O
+
+Reduction	O
+in	O
+caffeine	B-Chemical
+toxicity	B-Disease
+by	O
+acetaminophen	B-Chemical
+.	O
+
+A	O
+patient	O
+who	O
+allegedly	O
+consumed	O
+100	O
+tablets	O
+of	O
+an	O
+over	O
+-	O
+the	O
+-	O
+counter	O
+analgesic	O
+containing	O
+sodium	B-Chemical
+acetylsalicylate	I-Chemical
+,	O
+caffeine	B-Chemical
+,	O
+and	O
+acetaminophen	B-Chemical
+displayed	O
+no	O
+significant	O
+CNS	O
+stimulation	O
+despite	O
+the	O
+presence	O
+of	O
+175	O
+micrograms	O
+of	O
+caffeine	B-Chemical
+per	O
+mL	O
+of	O
+serum	O
+.	O
+
+Because	O
+salicylates	O
+have	O
+been	O
+reported	O
+to	O
+augment	O
+the	O
+stimulatory	O
+effects	O
+of	O
+caffeine	B-Chemical
+on	O
+the	O
+CNS	O
+,	O
+attention	O
+was	O
+focused	O
+on	O
+the	O
+possibility	O
+that	O
+the	O
+presence	O
+of	O
+acetaminophen	B-Chemical
+(	O
+52	O
+micrograms	O
+/	O
+mL	O
+)	O
+reduced	O
+the	O
+CNS	O
+toxicity	B-Disease
+of	O
+caffeine	B-Chemical
+.	O
+
+Studies	O
+in	O
+DBA	O
+/	O
+2J	O
+mice	O
+showed	O
+that	O
+:	O
+1	O
+)	O
+pretreatment	O
+with	O
+acetaminophen	B-Chemical
+(	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+increased	O
+the	O
+interval	O
+between	O
+the	O
+administration	O
+of	O
+caffeine	B-Chemical
+(	O
+300	O
+to	O
+450	O
+mg	O
+/	O
+kg	O
+IP	O
+)	O
+and	O
+the	O
+onset	O
+of	O
+fatal	O
+convulsions	B-Disease
+by	O
+a	O
+factor	O
+of	O
+about	O
+two	O
+;	O
+and	O
+2	O
+)	O
+pretreatment	O
+with	O
+acetaminophen	B-Chemical
+(	O
+75	O
+mg	O
+/	O
+kg	O
+)	O
+reduced	O
+the	O
+incidence	O
+of	O
+audiogenic	O
+seizures	B-Disease
+produced	O
+in	O
+the	O
+presence	O
+of	O
+caffeine	B-Chemical
+(	O
+12	O
+.	O
+5	O
+to	O
+75	O
+mg	O
+/	O
+kg	O
+IP	O
+)	O
+.	O
+
+The	O
+frequency	O
+of	O
+sound	O
+-	O
+induced	O
+seizures	B-Disease
+after	O
+12	O
+.	O
+5	O
+or	O
+25	O
+mg	O
+/	O
+kg	O
+caffeine	B-Chemical
+was	O
+reduced	O
+from	O
+50	O
+to	O
+5	O
+%	O
+by	O
+acetaminophen	B-Chemical
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+caffeine	B-Chemical
+,	O
+acetaminophen	B-Chemical
+(	O
+up	O
+to	O
+300	O
+mg	O
+/	O
+kg	O
+)	O
+did	O
+not	O
+modify	O
+the	O
+seizures	B-Disease
+induced	O
+by	O
+maximal	O
+electroshock	O
+and	O
+did	O
+not	O
+alter	O
+the	O
+convulsant	O
+dose	O
+of	O
+pentylenetetrezol	B-Chemical
+in	O
+mice	O
+(	O
+tests	O
+performed	O
+by	O
+the	O
+Anticonvulsant	O
+Screening	O
+Project	O
+of	O
+NINCDS	O
+)	O
+.	O
+
+Acetaminophen	B-Chemical
+(	O
+up	O
+to	O
+150	O
+micrograms	O
+/	O
+mL	O
+)	O
+did	O
+not	O
+retard	O
+the	O
+incorporation	O
+of	O
+radioactive	O
+adenosine	B-Chemical
+into	O
+ATP	B-Chemical
+in	O
+slices	O
+of	O
+rat	O
+cerebral	O
+cortex	O
+.	O
+
+Thus	O
+the	O
+mechanism	O
+by	O
+which	O
+acetaminophen	B-Chemical
+antagonizes	O
+the	O
+actions	O
+of	O
+caffeine	B-Chemical
+in	O
+the	O
+CNS	O
+remains	O
+unknown	O
+.	O
+
+A	O
+double	O
+-	O
+blind	O
+study	O
+of	O
+the	O
+efficacy	O
+and	O
+safety	O
+of	O
+dothiepin	B-Chemical
+hydrochloride	I-Chemical
+in	O
+the	O
+treatment	O
+of	O
+major	O
+depressive	B-Disease
+disorder	I-Disease
+.	O
+
+In	O
+a	O
+6	O
+-	O
+week	O
+double	O
+-	O
+blind	O
+parallel	O
+treatment	O
+study	O
+,	O
+dothiepin	B-Chemical
+and	O
+amitriptyline	B-Chemical
+were	O
+compared	O
+to	O
+placebo	O
+in	O
+the	O
+treatment	O
+of	O
+33	O
+depressed	B-Disease
+outpatients	O
+.	O
+
+Dothiepin	B-Chemical
+and	O
+amitriptyline	B-Chemical
+were	O
+equally	O
+effective	O
+in	O
+alleviating	O
+the	O
+symptoms	O
+of	O
+depressive	B-Disease
+illness	I-Disease
+,	O
+and	O
+both	O
+were	O
+significantly	O
+superior	O
+to	O
+placebo	O
+.	O
+
+The	O
+overall	O
+incidence	O
+of	O
+side	O
+effects	O
+and	O
+the	O
+frequency	O
+and	O
+severity	O
+of	O
+blurred	B-Disease
+vision	I-Disease
+,	O
+dry	B-Disease
+mouth	I-Disease
+,	O
+and	O
+drowsiness	O
+were	O
+significantly	O
+less	O
+with	O
+dothiepin	B-Chemical
+than	O
+with	O
+amitriptyline	B-Chemical
+.	O
+
+Dothiepin	B-Chemical
+also	O
+produced	O
+fewer	O
+CNS	O
+and	O
+cardiovascular	O
+effects	O
+.	O
+
+There	O
+were	O
+no	O
+clinically	O
+important	O
+changes	O
+in	O
+laboratory	O
+parameters	O
+.	O
+
+Dothiepin	B-Chemical
+thus	O
+was	O
+found	O
+to	O
+be	O
+an	O
+effective	O
+antidepressant	B-Chemical
+drug	O
+associated	O
+with	O
+fewer	O
+side	O
+effects	O
+than	O
+amitriptyline	B-Chemical
+in	O
+the	O
+treatment	O
+of	O
+depressed	B-Disease
+outpatients	O
+.	O
+
+Behavioral	O
+effects	O
+of	O
+diazepam	B-Chemical
+and	O
+propranolol	B-Chemical
+in	O
+patients	O
+with	O
+panic	B-Disease
+disorder	I-Disease
+and	O
+agoraphobia	B-Disease
+.	O
+
+The	O
+effects	O
+of	O
+oral	O
+doses	O
+of	O
+diazepam	B-Chemical
+(	O
+single	O
+dose	O
+of	O
+10	O
+mg	O
+and	O
+a	O
+median	O
+dose	O
+of	O
+30	O
+mg	O
+/	O
+day	O
+for	O
+2	O
+weeks	O
+)	O
+and	O
+propranolol	B-Chemical
+(	O
+single	O
+dose	O
+of	O
+80	O
+mg	O
+and	O
+a	O
+median	O
+dose	O
+of	O
+240	O
+mg	O
+/	O
+day	O
+for	O
+2	O
+weeks	O
+)	O
+on	O
+psychological	O
+performance	O
+of	O
+patients	O
+with	O
+panic	B-Disease
+disorders	I-Disease
+and	O
+agoraphobia	B-Disease
+were	O
+investigated	O
+in	O
+a	O
+double	O
+-	O
+blind	O
+,	O
+randomized	O
+and	O
+crossover	O
+design	O
+.	O
+
+Both	O
+drugs	O
+impaired	B-Disease
+immediate	I-Disease
+free	I-Disease
+recall	I-Disease
+but	O
+the	O
+decrease	O
+was	O
+greater	O
+for	O
+diazepam	B-Chemical
+than	O
+propranolol	B-Chemical
+.	O
+
+Delayed	B-Disease
+free	I-Disease
+recall	I-Disease
+was	I-Disease
+also	I-Disease
+impaired	I-Disease
+but	O
+the	O
+two	O
+drugs	O
+did	O
+not	O
+differ	O
+.	O
+
+Patients	O
+tapped	O
+faster	O
+after	O
+propranolol	B-Chemical
+than	O
+diazepam	B-Chemical
+and	O
+they	O
+were	O
+more	O
+sedated	O
+after	O
+diazepam	B-Chemical
+than	O
+propranolol	B-Chemical
+.	O
+
+After	O
+2	O
+weeks	O
+of	O
+treatment	O
+,	O
+patients	O
+tested	O
+5	O
+-	O
+8	O
+h	O
+after	O
+the	O
+last	O
+dose	O
+of	O
+medication	O
+did	O
+not	O
+show	O
+any	O
+decrement	O
+of	O
+performance	O
+.	O
+
+These	O
+results	O
+are	O
+similar	O
+to	O
+those	O
+previously	O
+found	O
+in	O
+healthy	O
+subjects	O
+.	O
+
+Accumulation	O
+of	O
+drugs	O
+was	O
+not	O
+reflected	O
+in	O
+prolonged	O
+behavioral	B-Disease
+impairment	I-Disease
+.	O
+
+Comparison	O
+of	O
+i	O
+.	O
+v	O
+.	O
+glycopyrrolate	B-Chemical
+and	O
+atropine	B-Chemical
+in	O
+the	O
+prevention	O
+of	O
+bradycardia	B-Disease
+and	O
+arrhythmias	B-Disease
+following	O
+repeated	O
+doses	O
+of	O
+suxamethonium	B-Chemical
+in	O
+children	O
+.	O
+
+The	O
+effectiveness	O
+of	O
+administration	O
+of	O
+glycopyrrolate	B-Chemical
+5	O
+and	O
+10	O
+micrograms	O
+kg	O
+-	O
+1	O
+and	O
+atropine	B-Chemical
+10	O
+and	O
+20	O
+micrograms	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+v	O
+.	O
+immediately	O
+before	O
+the	O
+induction	O
+of	O
+anaesthesia	O
+,	O
+to	O
+prevent	O
+arrhythmia	B-Disease
+and	O
+bradycardia	B-Disease
+following	O
+repeated	O
+doses	O
+of	O
+suxamethonium	B-Chemical
+in	O
+children	O
+,	O
+was	O
+studied	O
+.	O
+
+A	O
+control	O
+group	O
+was	O
+included	O
+for	O
+comparison	O
+with	O
+the	O
+lower	O
+dose	O
+range	O
+of	O
+glycopyrrolate	B-Chemical
+and	O
+atropine	B-Chemical
+.	O
+
+A	O
+frequency	O
+of	O
+bradycardia	B-Disease
+of	O
+50	O
+%	O
+was	O
+noted	O
+in	O
+the	O
+control	O
+group	O
+,	O
+but	O
+this	O
+was	O
+not	O
+significantly	O
+different	O
+from	O
+the	O
+frequency	O
+with	O
+the	O
+active	O
+drugs	O
+.	O
+
+Bradycardia	B-Disease
+(	O
+defined	O
+as	O
+a	O
+decrease	O
+in	O
+heart	O
+rate	O
+to	O
+less	O
+than	O
+50	O
+beat	O
+min	O
+-	O
+1	O
+)	O
+was	O
+prevented	O
+when	O
+the	O
+larger	O
+dose	O
+of	O
+either	O
+active	O
+drug	O
+was	O
+used	O
+.	O
+
+It	O
+is	O
+recommended	O
+that	O
+either	O
+glycopyrrolate	B-Chemical
+10	O
+micrograms	O
+kg	O
+-	O
+1	O
+or	O
+atropine	B-Chemical
+20	O
+micrograms	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+v	O
+.	O
+should	O
+immediately	O
+precede	O
+induction	O
+of	O
+anaesthesia	O
+,	O
+in	O
+children	O
+,	O
+if	O
+the	O
+repeated	O
+administration	O
+of	O
+suxamethonium	B-Chemical
+is	O
+anticipated	O
+.	O
+
+Veno	B-Disease
+-	I-Disease
+occlusive	I-Disease
+liver	I-Disease
+disease	I-Disease
+after	O
+dacarbazine	B-Chemical
+therapy	O
+(	O
+DTIC	B-Chemical
+)	O
+for	O
+melanoma	B-Disease
+.	O
+
+A	O
+case	O
+of	O
+veno	B-Disease
+-	I-Disease
+occlusive	I-Disease
+disease	I-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+with	O
+fatal	O
+outcome	O
+after	O
+dacarbazine	B-Chemical
+(	O
+DTIC	B-Chemical
+)	O
+therapy	O
+for	O
+melanoma	B-Disease
+is	O
+reported	O
+.	O
+
+There	O
+was	O
+a	O
+fulminant	O
+clinical	O
+course	O
+from	O
+start	O
+of	O
+symptoms	O
+until	O
+death	B-Disease
+.	O
+
+At	O
+autopsy	O
+the	O
+liver	O
+was	O
+enlarged	O
+and	O
+firm	O
+with	O
+signs	O
+of	O
+venous	B-Disease
+congestion	I-Disease
+.	O
+
+Small	O
+-	O
+and	O
+medium	O
+-	O
+sized	O
+hepatic	O
+veins	O
+were	O
+blocked	O
+by	O
+thrombosis	B-Disease
+.	O
+
+Eosinophilic	O
+infiltrations	O
+were	O
+found	O
+around	O
+the	O
+vessels	O
+.	O
+
+Published	O
+cases	O
+from	O
+the	O
+literature	O
+are	O
+reviewed	O
+and	O
+pertinent	O
+features	O
+discussed	O
+.	O
+
+Maternal	O
+lithium	B-Chemical
+and	O
+neonatal	O
+Ebstein	B-Disease
+'	I-Disease
+s	I-Disease
+anomaly	I-Disease
+:	O
+evaluation	O
+with	O
+cross	O
+-	O
+sectional	O
+echocardiography	O
+.	O
+
+Cross	O
+-	O
+sectional	O
+echocardiography	O
+was	O
+used	O
+to	O
+evaluate	O
+two	O
+neonates	O
+whose	O
+mothers	O
+ingested	O
+lithium	B-Chemical
+during	O
+pregnancy	O
+.	O
+
+In	O
+one	O
+infant	O
+,	O
+Ebstein	B-Disease
+'	I-Disease
+s	I-Disease
+anomaly	I-Disease
+of	O
+the	O
+tricuspid	O
+valve	O
+was	O
+identified	O
+.	O
+
+In	O
+the	O
+other	O
+infant	O
+cross	O
+-	O
+sectional	O
+echocardiography	O
+provided	O
+reassurance	O
+that	O
+the	O
+infant	O
+did	O
+not	O
+have	O
+Ebstein	B-Disease
+'	I-Disease
+s	I-Disease
+anomaly	I-Disease
+.	O
+
+Cross	O
+-	O
+sectional	O
+echocardiographic	O
+screening	O
+of	O
+newborns	O
+exposed	O
+to	O
+lithium	B-Chemical
+during	O
+gestation	O
+can	O
+provide	O
+highly	O
+accurate	O
+,	O
+noninvasive	O
+assessment	O
+of	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+lithium	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+malformations	I-Disease
+.	O
+
+Effects	O
+of	O
+training	O
+on	O
+the	O
+extent	O
+of	O
+experimental	O
+myocardial	B-Disease
+infarction	I-Disease
+in	O
+aging	O
+rats	O
+.	O
+
+The	O
+effects	O
+of	O
+exercise	O
+on	O
+the	O
+severity	O
+of	O
+isoproterenol	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+infarction	I-Disease
+were	O
+studied	O
+in	O
+female	O
+albino	O
+rats	O
+of	O
+20	O
+,	O
+40	O
+,	O
+60	O
+and	O
+80	O
+weeks	O
+of	O
+age	O
+.	O
+
+The	O
+rats	O
+were	O
+trained	O
+to	O
+swim	O
+for	O
+a	O
+specific	O
+duration	O
+and	O
+for	O
+a	O
+particular	O
+period	O
+.	O
+
+The	O
+occurrence	O
+of	O
+infarcts	B-Disease
+were	O
+confirmed	O
+by	O
+histological	O
+methods	O
+.	O
+
+Elevations	O
+in	O
+the	O
+serum	O
+GOT	O
+and	O
+GPT	O
+were	O
+maximum	O
+in	O
+the	O
+sedentary	O
+-	O
+isoproterenols	B-Chemical
+and	O
+minimum	O
+in	O
+the	O
+exercise	O
+-	O
+controls	O
+.	O
+
+These	O
+changes	O
+in	O
+the	O
+serum	O
+transaminases	O
+were	O
+associated	O
+with	O
+corresponding	O
+depletions	O
+in	O
+the	O
+cardiac	O
+GOT	O
+and	O
+GPT	O
+.	O
+
+However	O
+,	O
+age	O
+was	O
+seen	O
+to	O
+interfere	O
+with	O
+the	O
+responses	O
+exhibited	O
+by	O
+the	O
+young	O
+and	O
+old	O
+rats	O
+.	O
+
+Studies	O
+dealing	O
+with	O
+myocardial	B-Disease
+infarction	I-Disease
+are	O
+more	O
+informative	O
+when	O
+dealt	O
+with	O
+age	O
+.	O
+
+Effect	O
+of	O
+polyethylene	B-Chemical
+glycol	I-Chemical
+400	I-Chemical
+on	O
+adriamycin	B-Chemical
+toxicity	B-Disease
+in	O
+mice	O
+.	O
+
+The	O
+effect	O
+of	O
+a	O
+widely	O
+used	O
+organic	O
+solvent	O
+,	O
+polyethylene	B-Chemical
+glycol	I-Chemical
+400	I-Chemical
+(	O
+PEG	B-Chemical
+400	I-Chemical
+)	O
+,	O
+on	O
+the	O
+toxic	O
+action	O
+of	O
+an	O
+acute	O
+or	O
+chronic	O
+treatment	O
+with	O
+adriamycin	B-Chemical
+(	O
+ADR	B-Chemical
+)	O
+was	O
+evaluated	O
+in	O
+mice	O
+.	O
+
+PEG	B-Chemical
+400	I-Chemical
+impressively	O
+decreased	O
+both	O
+acute	O
+high	O
+-	O
+dose	O
+and	O
+chronic	O
+low	O
+-	O
+dose	O
+-	O
+ADR	B-Chemical
+-	O
+associated	O
+lethality	O
+.	O
+
+Light	O
+microscopic	O
+analysis	O
+showed	O
+a	O
+significant	O
+protection	O
+against	O
+ADR	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+morphological	I-Disease
+alterations	I-Disease
+.	O
+
+Such	O
+treatment	O
+did	O
+not	O
+diminish	O
+the	O
+ADR	B-Chemical
+antitumor	O
+activity	O
+in	O
+L1210	B-Disease
+leukemia	I-Disease
+and	O
+in	O
+Ehrlich	B-Disease
+ascites	I-Disease
+tumor	I-Disease
+.	O
+
+Sublingual	O
+absorption	O
+of	O
+the	O
+quaternary	B-Chemical
+ammonium	I-Chemical
+antiarrhythmic	O
+agent	O
+,	O
+UM	B-Chemical
+-	I-Chemical
+272	I-Chemical
+.	O
+
+UM	B-Chemical
+-	I-Chemical
+272	I-Chemical
+(	O
+N	B-Chemical
+,	I-Chemical
+N	I-Chemical
+-	I-Chemical
+dimethylpropranolol	I-Chemical
+)	O
+,	O
+a	O
+quaternary	O
+antiarrhythmic	O
+agent	O
+,	O
+was	O
+administered	O
+sublingually	O
+to	O
+dogs	O
+with	O
+ouabain	B-Chemical
+-	O
+induced	O
+ventricular	B-Disease
+tachycardias	I-Disease
+.	O
+
+Both	O
+anti	O
+-	O
+arrhythmic	O
+efficacy	O
+and	O
+bioavailability	O
+were	O
+compared	O
+to	O
+oral	O
+drug	O
+.	O
+
+Sublingual	O
+UM	B-Chemical
+-	I-Chemical
+272	I-Chemical
+converted	O
+ventricular	B-Disease
+tachycardia	I-Disease
+to	O
+sinus	O
+rhythm	O
+in	O
+all	O
+5	O
+dogs	O
+.	O
+
+The	O
+area	O
+under	O
+the	O
+plasma	O
+concentration	O
+time	O
+curve	O
+at	O
+90	O
+min	O
+was	O
+4	O
+-	O
+12	O
+times	O
+greater	O
+than	O
+for	O
+oral	O
+drug	O
+,	O
+suggesting	O
+the	O
+existence	O
+of	O
+an	O
+absorption	O
+-	O
+limiting	O
+process	O
+in	O
+the	O
+intestine	O
+,	O
+and	O
+providing	O
+an	O
+alternate	O
+form	O
+of	O
+administration	O
+for	O
+quaternary	O
+drugs	O
+.	O
+
+Early	O
+adjuvant	O
+adriamycin	B-Chemical
+in	O
+superficial	O
+bladder	B-Disease
+carcinoma	I-Disease
+.	O
+
+A	O
+multicenter	O
+study	O
+was	O
+performed	O
+in	O
+110	O
+patients	O
+with	O
+superficial	O
+transitional	O
+cell	O
+carcinoma	B-Disease
+of	I-Disease
+the	I-Disease
+bladder	I-Disease
+.	O
+
+Adriamycin	B-Chemical
+(	O
+50	O
+mg	O
+/	O
+50	O
+ml	O
+)	O
+was	O
+administered	O
+intravesically	O
+within	O
+24	O
+h	O
+after	O
+transurethral	O
+resection	O
+of	O
+TA	O
+-	O
+T1	O
+(	O
+O	O
+-	O
+A	O
+)	O
+bladder	B-Disease
+tumors	I-Disease
+.	O
+
+Instillation	O
+was	O
+repeated	O
+twice	O
+during	O
+the	O
+first	O
+week	O
+,	O
+then	O
+weekly	O
+during	O
+the	O
+first	O
+month	O
+and	O
+afterwards	O
+monthly	O
+for	O
+1	O
+year	O
+.	O
+
+The	O
+tolerance	O
+was	O
+evaluated	O
+in	O
+these	O
+110	O
+patients	O
+,	O
+and	O
+29	O
+patients	O
+presented	O
+with	O
+local	O
+side	O
+-	O
+effects	O
+.	O
+
+In	O
+24	O
+of	O
+these	O
+patients	O
+chemical	O
+cystitis	B-Disease
+was	O
+severe	O
+enough	O
+for	O
+them	O
+to	O
+drop	O
+out	O
+of	O
+the	O
+study	O
+.	O
+
+No	O
+systemic	O
+side	O
+-	O
+effects	O
+were	O
+observed	O
+.	O
+
+Recurrence	O
+was	O
+studied	O
+in	O
+82	O
+evaluable	O
+patients	O
+after	O
+1	O
+year	O
+of	O
+follow	O
+-	O
+up	O
+and	O
+in	O
+72	O
+patients	O
+followed	O
+for	O
+2	O
+-	O
+3	O
+years	O
+(	O
+mean	O
+32	O
+months	O
+)	O
+.	O
+
+Of	O
+the	O
+82	O
+patients	O
+studied	O
+after	O
+1	O
+year	O
+,	O
+23	O
+had	O
+primary	O
+and	O
+59	O
+recurrent	O
+disease	O
+.	O
+
+Of	O
+the	O
+82	O
+evaluable	O
+patients	O
+,	O
+50	O
+did	O
+not	O
+show	O
+any	O
+recurrence	O
+after	O
+1	O
+year	O
+(	O
+61	O
+%	O
+)	O
+,	O
+while	O
+32	O
+presented	O
+with	O
+one	O
+or	O
+more	O
+recurrences	O
+(	O
+39	O
+%	O
+)	O
+.	O
+
+Of	O
+these	O
+recurrences	O
+,	O
+27	O
+were	O
+T1	O
+tumors	B-Disease
+while	O
+five	O
+progressed	O
+to	O
+more	O
+highly	O
+invasive	O
+lesions	O
+.	O
+
+In	O
+patients	O
+that	O
+were	O
+free	O
+of	O
+recurrence	O
+during	O
+the	O
+first	O
+year	O
+,	O
+80	O
+%	O
+remained	O
+tumor	B-Disease
+-	O
+free	O
+during	O
+the	O
+2	O
+-	O
+to	O
+3	O
+-	O
+year	O
+follow	O
+-	O
+up	O
+period	O
+.	O
+
+Of	O
+the	O
+patients	O
+developing	O
+one	O
+or	O
+more	O
+recurrences	O
+during	O
+the	O
+first	O
+year	O
+,	O
+only	O
+50	O
+%	O
+presented	O
+with	O
+further	O
+recurrence	O
+once	O
+the	O
+instillations	O
+were	O
+stopped	O
+.	O
+
+The	O
+beneficial	O
+effect	O
+of	O
+Adriamycin	B-Chemical
+appears	O
+obvious	O
+and	O
+might	O
+be	O
+related	O
+to	O
+the	O
+drug	O
+itself	O
+,	O
+the	O
+early	O
+and	O
+repeated	O
+instillations	O
+after	O
+TUR	O
+,	O
+or	O
+both	O
+.	O
+
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+-	O
+induced	O
+angiopathy	B-Disease
+in	O
+rats	O
+.	O
+
+The	O
+effect	O
+of	O
+high	O
+dose	O
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+treatment	O
+on	O
+aortic	O
+permeability	O
+to	O
+albumin	O
+and	O
+on	O
+the	O
+ultrastructure	O
+of	O
+the	O
+vessel	O
+.	O
+
+Male	O
+Sprague	O
+-	O
+Dawley	O
+rats	O
+were	O
+treated	O
+with	O
+D	B-Chemical
+-	I-Chemical
+penicillamine	I-Chemical
+(	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+)	O
+500	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+for	O
+10	O
+or	O
+42	O
+days	O
+.	O
+
+Pair	O
+fed	O
+rats	O
+served	O
+as	O
+controls	O
+.	O
+
+Changes	O
+in	O
+aortic	O
+morphology	O
+were	O
+examined	O
+by	O
+light	O
+-	O
+and	O
+transmission	O
+-	O
+electron	O
+microscopy	O
+(	O
+TEM	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+endothelial	O
+permeability	O
+and	O
+the	O
+penetration	O
+through	O
+the	O
+aortic	O
+wall	O
+of	O
+albumin	O
+were	O
+studied	O
+10	O
+minutes	O
+,	O
+24	O
+and	O
+48	O
+hours	O
+after	O
+i	O
+.	O
+v	O
+.	O
+injection	O
+of	O
+human	O
+serum	O
+131I	O
+-	O
+albumin	O
+(	O
+131I	O
+-	O
+HSA	O
+)	O
+.	O
+
+TEM	O
+revealed	O
+extensive	O
+elastolysis	O
+in	O
+the	O
+arterial	O
+wall	O
+of	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+-	O
+treated	O
+rats	O
+,	O
+consistent	O
+with	O
+an	O
+inhibitory	O
+effect	O
+on	O
+crosslink	O
+formation	O
+.	O
+
+In	O
+experimental	O
+animals	O
+excess	O
+deposition	O
+of	O
+collagen	O
+and	O
+glycoaminoglycans	O
+was	O
+observed	O
+in	O
+the	O
+subendothelial	O
+and	O
+medial	O
+layer	O
+of	O
+the	O
+aortic	O
+wall	O
+,	O
+together	O
+with	O
+prominent	O
+basal	O
+membrane	O
+substance	O
+around	O
+aortic	O
+smooth	O
+muscle	O
+cells	O
+.	O
+
+The	O
+aorta	O
+/	O
+serum	O
+-	O
+ratio	O
+and	O
+the	O
+radioactive	O
+build	O
+-	O
+up	O
+24	O
+and	O
+48	O
+hours	O
+after	O
+injection	O
+of	O
+131I	O
+-	O
+HSA	O
+was	O
+reduced	O
+in	O
+animals	O
+treated	O
+with	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+for	O
+42	O
+days	O
+,	O
+indicating	O
+an	O
+impeded	O
+transmural	O
+transport	O
+of	O
+tracer	O
+which	O
+may	O
+be	O
+caused	O
+by	O
+a	O
+steric	O
+exclusion	O
+effect	O
+of	O
+abundant	O
+hyaluronate	B-Chemical
+.	O
+
+The	O
+endothelial	O
+ultrastructure	O
+was	O
+unaffected	O
+by	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+,	O
+and	O
+no	O
+differences	O
+in	O
+aortic	O
+131I	O
+-	O
+HSA	O
+radioactivity	O
+or	O
+aorta	O
+/	O
+serum	O
+-	O
+ratio	O
+were	O
+recorded	O
+between	O
+experimental	O
+and	O
+control	O
+groups	O
+10	O
+minutes	O
+after	O
+tracer	O
+injection	O
+,	O
+indicating	O
+that	O
+the	O
+permeability	O
+of	O
+the	O
+endothelial	O
+barrier	O
+to	O
+albumin	O
+remained	O
+unaffected	O
+by	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+treatment	O
+.	O
+
+These	O
+observations	O
+support	O
+the	O
+hypothesis	O
+that	O
+treatment	O
+with	O
+high	O
+doses	O
+of	O
+D	B-Chemical
+-	I-Chemical
+pen	I-Chemical
+may	O
+induce	O
+a	O
+fibroproliferative	O
+response	O
+in	O
+rat	O
+aorta	O
+,	O
+possibly	O
+by	O
+an	O
+inhibitory	O
+effect	O
+on	O
+the	O
+cross	O
+-	O
+linking	O
+of	O
+collagen	O
+and	O
+elastin	O
+.	O
+
+Effect	O
+of	O
+aspirin	B-Chemical
+on	O
+N	B-Chemical
+-	I-Chemical
+[	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+5	I-Chemical
+-	I-Chemical
+nitro	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+furyl	I-Chemical
+)	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+thiazolyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+formamide	I-Chemical
+-	O
+induced	O
+epithelial	O
+proliferation	O
+in	O
+the	O
+urinary	O
+bladder	O
+and	O
+forestomach	O
+of	O
+the	O
+rat	O
+.	O
+
+The	O
+co	O
+-	O
+administration	O
+of	O
+aspirin	B-Chemical
+with	O
+N	B-Chemical
+-	I-Chemical
+[	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+5	I-Chemical
+-	I-Chemical
+nitro	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+furyl	I-Chemical
+)	I-Chemical
+-	I-Chemical
+2	I-Chemical
+-	I-Chemical
+thiazolyl	I-Chemical
+]	I-Chemical
+-	I-Chemical
+formamide	I-Chemical
+(	O
+FANFT	B-Chemical
+)	O
+to	O
+rats	O
+resulted	O
+in	O
+a	O
+reduced	O
+incidence	O
+of	O
+FANFT	B-Chemical
+-	O
+induced	O
+bladder	B-Disease
+carcinomas	I-Disease
+but	O
+a	O
+concomitant	O
+induction	O
+of	O
+forestomach	B-Disease
+tumors	I-Disease
+.	O
+
+An	O
+autoradiographic	O
+study	O
+was	O
+performed	O
+on	O
+male	O
+F	O
+-	O
+344	O
+rats	O
+fed	O
+diet	O
+containing	O
+FANFT	B-Chemical
+at	O
+a	O
+level	O
+of	O
+0	O
+.	O
+2	O
+%	O
+and	O
+/	O
+or	O
+aspirin	B-Chemical
+at	O
+a	O
+level	O
+of	O
+0	O
+.	O
+5	O
+%	O
+to	O
+evaluate	O
+the	O
+effect	O
+of	O
+aspirin	B-Chemical
+on	O
+the	O
+increased	O
+cell	O
+proliferation	O
+induced	O
+by	O
+FANFT	B-Chemical
+in	O
+the	O
+forestomach	O
+and	O
+bladder	O
+.	O
+
+FANFT	B-Chemical
+-	O
+induced	O
+cell	O
+proliferation	O
+in	O
+the	O
+bladder	O
+was	O
+significantly	O
+suppressed	O
+by	O
+aspirin	B-Chemical
+co	O
+-	O
+administration	O
+after	O
+4	O
+weeks	O
+but	O
+not	O
+after	O
+12	O
+weeks	O
+.	O
+
+In	O
+the	O
+forestomach	O
+,	O
+and	O
+also	O
+in	O
+the	O
+liver	O
+,	O
+aspirin	B-Chemical
+did	O
+not	O
+affect	O
+the	O
+FANFT	B-Chemical
+-	O
+induced	O
+increase	O
+in	O
+labeling	O
+index	O
+.	O
+
+The	O
+present	O
+results	O
+are	O
+consistent	O
+with	O
+the	O
+carcinogenicity	O
+experiment	O
+suggesting	O
+that	O
+different	O
+mechanisms	O
+are	O
+involved	O
+in	O
+FANFT	B-Chemical
+carcinogenesis	B-Disease
+in	O
+the	O
+bladder	O
+and	O
+forestomach	O
+,	O
+and	O
+that	O
+aspirin	B-Chemical
+'	O
+s	O
+effect	O
+on	O
+FANFT	B-Chemical
+in	O
+the	O
+forestomach	O
+is	O
+not	O
+due	O
+to	O
+an	O
+irritant	O
+effect	O
+associated	O
+with	O
+increased	O
+cell	O
+proliferation	O
+.	O
+
+Also	O
+,	O
+there	O
+appears	O
+to	O
+be	O
+an	O
+adaptation	O
+by	O
+the	O
+rats	O
+to	O
+the	O
+chronic	O
+ingestion	O
+of	O
+aspirin	B-Chemical
+.	O
+
+A	O
+case	O
+of	O
+tardive	B-Disease
+dyskinesia	I-Disease
+caused	O
+by	O
+metoclopramide	B-Chemical
+.	O
+
+Abnormal	B-Disease
+involuntary	I-Disease
+movements	I-Disease
+appeared	O
+in	O
+the	O
+mouth	O
+,	O
+tongue	O
+,	O
+neck	O
+and	O
+abdomen	O
+of	O
+a	O
+64	O
+-	O
+year	O
+-	O
+old	O
+male	O
+patient	O
+after	O
+he	O
+took	O
+metoclopramide	B-Chemical
+for	O
+gastrointestinal	B-Disease
+disorder	I-Disease
+in	O
+a	O
+regimen	O
+of	O
+30	O
+mg	O
+per	O
+day	O
+for	O
+a	O
+total	O
+of	O
+about	O
+260	O
+days	O
+.	O
+
+The	O
+symptoms	O
+exacerbated	O
+to	O
+a	O
+maximum	O
+in	O
+a	O
+month	O
+.	O
+
+When	O
+the	O
+metoclopramide	B-Chemical
+administration	O
+was	O
+discontinued	O
+,	O
+the	O
+abnormal	B-Disease
+movements	I-Disease
+gradually	O
+improved	O
+to	O
+a	O
+considerable	O
+extent	O
+.	O
+
+Attention	O
+to	O
+the	O
+possible	O
+induction	O
+of	O
+specific	O
+tardive	B-Disease
+dyskinesia	I-Disease
+is	O
+called	O
+for	O
+in	O
+the	O
+use	O
+of	O
+this	O
+drug	O
+.	O
+
+Intra	O
+-	O
+arterial	O
+BCNU	B-Chemical
+chemotherapy	O
+for	O
+treatment	O
+of	O
+malignant	B-Disease
+gliomas	I-Disease
+of	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Because	O
+of	O
+the	O
+rapid	O
+systemic	O
+clearance	O
+of	O
+BCNU	B-Chemical
+(	O
+1	B-Chemical
+,	I-Chemical
+3	I-Chemical
+-	I-Chemical
+bis	I-Chemical
+-	I-Chemical
+(	I-Chemical
+2	I-Chemical
+-	I-Chemical
+chloroethyl	I-Chemical
+)	I-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+nitrosourea	I-Chemical
+)	O
+,	O
+intra	O
+-	O
+arterial	O
+administration	O
+should	O
+provide	O
+a	O
+substantial	O
+advantage	O
+over	O
+intravenous	O
+administration	O
+for	O
+the	O
+treatment	O
+of	O
+malignant	B-Disease
+gliomas	I-Disease
+.	O
+
+Thirty	O
+-	O
+six	O
+patients	O
+were	O
+treated	O
+with	O
+BCNU	B-Chemical
+every	O
+6	O
+to	O
+8	O
+weeks	O
+,	O
+either	O
+by	O
+transfemoral	O
+catheterization	O
+of	O
+the	O
+internal	O
+carotid	O
+or	O
+vertebral	O
+artery	O
+or	O
+through	O
+a	O
+fully	O
+implantable	O
+intracarotid	O
+drug	O
+delivery	O
+system	O
+,	O
+beginning	O
+with	O
+a	O
+dose	O
+of	O
+200	O
+mg	O
+/	O
+sq	O
+m	O
+body	O
+surface	O
+area	O
+.	O
+
+Twelve	O
+patients	O
+with	O
+Grade	O
+III	O
+or	O
+IV	O
+astrocytomas	B-Disease
+were	O
+treated	O
+after	O
+partial	O
+resection	O
+of	O
+the	O
+tumor	B-Disease
+without	O
+prior	O
+radiation	O
+therapy	O
+.	O
+
+After	O
+two	O
+to	O
+seven	O
+cycles	O
+of	O
+chemotherapy	O
+,	O
+nine	O
+patients	O
+showed	O
+a	O
+decrease	O
+in	O
+tumor	B-Disease
+size	O
+and	O
+surrounding	O
+edema	B-Disease
+on	O
+contrast	O
+-	O
+enhanced	O
+computerized	O
+tomography	O
+scans	O
+.	O
+
+In	O
+the	O
+nine	O
+responders	O
+,	O
+median	O
+duration	O
+of	O
+chemotherapy	O
+response	O
+from	O
+the	O
+time	O
+of	O
+operation	O
+was	O
+25	O
+weeks	O
+(	O
+range	O
+12	O
+to	O
+more	O
+than	O
+91	O
+weeks	O
+)	O
+.	O
+
+The	O
+median	O
+duration	O
+of	O
+survival	O
+in	O
+the	O
+12	O
+patients	O
+was	O
+54	O
+weeks	O
+(	O
+range	O
+21	O
+to	O
+more	O
+than	O
+156	O
+weeks	O
+)	O
+,	O
+with	O
+an	O
+18	O
+-	O
+month	O
+survival	O
+rate	O
+of	O
+42	O
+%	O
+.	O
+
+Twenty	O
+-	O
+four	O
+patients	O
+with	O
+recurrent	O
+Grade	O
+I	O
+to	O
+IV	O
+astrocytomas	B-Disease
+,	O
+whose	O
+resection	O
+and	O
+irradiation	O
+therapy	O
+had	O
+failed	O
+,	O
+received	O
+two	O
+to	O
+eight	O
+courses	O
+of	O
+intra	O
+-	O
+arterial	O
+BCNU	B-Chemical
+therapy	O
+.	O
+
+Seventeen	O
+of	O
+these	O
+had	O
+a	O
+response	O
+or	O
+were	O
+stable	O
+for	O
+a	O
+median	O
+of	O
+20	O
+weeks	O
+(	O
+range	O
+6	O
+to	O
+more	O
+than	O
+66	O
+weeks	O
+)	O
+.	O
+
+The	O
+catheterization	O
+procedure	O
+is	O
+safe	O
+,	O
+with	O
+no	O
+immediate	O
+complication	O
+in	O
+111	O
+infusions	O
+of	O
+BCNU	B-Chemical
+.	O
+
+A	O
+delayed	O
+complication	O
+in	O
+nine	O
+patients	O
+has	O
+been	O
+unilateral	O
+loss	B-Disease
+of	I-Disease
+vision	I-Disease
+secondary	O
+to	O
+a	O
+retinal	B-Disease
+vasculitis	I-Disease
+.	O
+
+The	O
+frequency	O
+of	O
+visual	B-Disease
+loss	I-Disease
+decreased	O
+after	O
+the	O
+concentration	O
+of	O
+the	O
+ethanol	B-Chemical
+diluent	O
+was	O
+lowered	O
+.	O
+
+Provocation	O
+of	O
+postural	O
+hypotension	B-Disease
+by	O
+nitroglycerin	B-Chemical
+in	O
+diabetic	B-Disease
+autonomic	I-Disease
+neuropathy	I-Disease
+?	O
+
+The	O
+effect	O
+of	O
+nitroglycerin	B-Chemical
+on	O
+heart	O
+rate	O
+and	O
+systolic	O
+blood	O
+pressure	O
+was	O
+compared	O
+in	O
+5	O
+normal	O
+subjects	O
+,	O
+12	O
+diabetic	B-Disease
+subjects	O
+without	O
+autonomic	B-Disease
+neuropathy	I-Disease
+,	O
+and	O
+5	O
+diabetic	B-Disease
+subjects	O
+with	O
+autonomic	B-Disease
+neuropathy	I-Disease
+.	O
+
+The	O
+magnitude	O
+and	O
+time	O
+course	O
+of	O
+the	O
+increase	O
+in	O
+heart	O
+rate	O
+and	O
+the	O
+decrease	O
+in	O
+systolic	O
+blood	O
+pressure	O
+after	O
+nitroglycerin	B-Chemical
+were	O
+similar	O
+in	O
+the	O
+normal	O
+and	O
+diabetic	B-Disease
+subjects	O
+without	O
+autonomic	B-Disease
+neuropathy	I-Disease
+,	O
+whereas	O
+a	O
+lesser	O
+increase	O
+in	O
+heart	O
+rate	O
+and	O
+a	O
+greater	O
+decrease	O
+in	O
+systolic	O
+blood	O
+pressure	O
+occurred	O
+in	O
+the	O
+diabetic	B-Disease
+subjects	O
+with	O
+autonomic	B-Disease
+neuropathy	I-Disease
+.	O
+
+It	O
+is	O
+therefore	O
+suggested	O
+that	O
+caution	O
+should	O
+be	O
+exercised	O
+when	O
+prescribing	O
+vasodilator	O
+drugs	O
+in	O
+diabetic	B-Disease
+patients	O
+,	O
+particularly	O
+those	O
+with	O
+autonomic	B-Disease
+neuropathy	I-Disease
+.	O
+
+Blood	O
+pressure	O
+response	O
+to	O
+chronic	O
+low	O
+-	O
+dose	O
+intrarenal	O
+noradrenaline	B-Chemical
+infusion	O
+in	O
+conscious	O
+rats	O
+.	O
+
+Sodium	B-Chemical
+chloride	I-Chemical
+solution	O
+(	O
+0	O
+.	O
+9	O
+%	O
+)	O
+or	O
+noradrenaline	B-Chemical
+in	O
+doses	O
+of	O
+4	O
+,	O
+12	O
+and	O
+36	O
+micrograms	O
+h	O
+-	O
+1	O
+kg	O
+-	O
+1	O
+was	O
+infused	O
+for	O
+five	O
+consecutive	O
+days	O
+,	O
+either	O
+intrarenally	O
+(	O
+by	O
+a	O
+new	O
+technique	O
+)	O
+or	O
+intravenously	O
+into	O
+rats	O
+with	O
+one	O
+kidney	O
+removed	O
+.	O
+
+Intrarenal	O
+infusion	O
+of	O
+noradrenaline	B-Chemical
+caused	O
+hypertension	B-Disease
+at	O
+doses	O
+which	O
+did	O
+not	O
+do	O
+so	O
+when	O
+infused	O
+intravenously	O
+.	O
+
+Intrarenal	O
+compared	O
+with	O
+intravenous	O
+infusion	O
+of	O
+noradrenaline	B-Chemical
+caused	O
+higher	O
+plasma	O
+noradrenaline	B-Chemical
+concentrations	O
+and	O
+a	O
+shift	O
+of	O
+the	O
+plasma	O
+noradrenaline	B-Chemical
+concentration	O
+-	O
+blood	O
+pressure	O
+effect	O
+curve	O
+towards	O
+lower	O
+plasma	O
+noradrenaline	B-Chemical
+levels	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+hypertension	B-Disease
+after	O
+chronic	O
+intrarenal	O
+noradrenaline	B-Chemical
+infusion	O
+is	O
+produced	O
+by	O
+relatively	O
+higher	O
+levels	O
+of	O
+circulating	O
+noradrenaline	B-Chemical
+and	O
+by	O
+triggering	O
+of	O
+an	O
+additional	O
+intrarenal	O
+pressor	O
+mechanism	O
+.	O
+
+Characterization	O
+of	O
+estrogen	B-Chemical
+-	O
+induced	O
+adenohypophyseal	B-Disease
+tumors	I-Disease
+in	O
+the	O
+Fischer	O
+344	O
+rat	O
+.	O
+
+Pituitary	B-Disease
+tumors	I-Disease
+were	O
+induced	O
+in	O
+F344	O
+female	O
+rats	O
+by	O
+chronic	O
+treatment	O
+with	O
+diethylstilbestrol	B-Chemical
+(	O
+DES	B-Chemical
+,	O
+8	O
+-	O
+10	O
+mg	O
+)	O
+implanted	O
+subcutaneously	O
+in	O
+silastic	O
+capsules	O
+.	O
+
+Over	O
+a	O
+range	O
+of	O
+1	O
+-	O
+150	O
+days	O
+of	O
+DES	B-Chemical
+treatment	O
+,	O
+pairs	O
+of	O
+control	O
+and	O
+DES	B-Chemical
+-	O
+treated	O
+rats	O
+were	O
+sacrificed	O
+,	O
+and	O
+their	O
+pituitaries	O
+dissociated	O
+enzymatically	O
+into	O
+single	O
+-	O
+cell	O
+preparations	O
+.	O
+
+The	O
+cell	O
+populations	O
+were	O
+examined	O
+regarding	O
+total	O
+cell	O
+recovery	O
+correlated	O
+with	O
+gland	O
+weight	O
+,	O
+intracellular	O
+prolactin	O
+(	O
+PRL	O
+)	O
+content	O
+and	O
+subsequent	O
+release	O
+in	O
+primary	O
+culture	O
+,	O
+immunocytochemical	O
+PRL	O
+staining	O
+,	O
+density	O
+and	O
+/	O
+or	O
+size	O
+alterations	O
+via	O
+separation	O
+on	O
+Ficoll	O
+-	O
+Hypaque	O
+and	O
+by	O
+unit	O
+gravity	O
+sedimentation	O
+,	O
+and	O
+cell	O
+cycle	O
+analysis	O
+,	O
+after	O
+acriflavine	B-Chemical
+DNA	O
+staining	O
+,	O
+by	O
+laser	O
+flow	O
+cytometry	O
+.	O
+
+Total	O
+cell	O
+yields	O
+from	O
+DES	B-Chemical
+-	O
+treated	O
+pituitaries	O
+increased	O
+from	O
+1	O
+.	O
+3	O
+times	O
+control	O
+yields	O
+at	O
+8	O
+days	O
+of	O
+treatment	O
+to	O
+58	O
+.	O
+9	O
+times	O
+control	O
+values	O
+by	O
+day	O
+150	O
+.	O
+
+Intracellular	O
+PRL	O
+content	O
+ranged	O
+from	O
+1	O
+.	O
+9	O
+to	O
+9	O
+.	O
+4	O
+times	O
+control	O
+levels	O
+,	O
+and	O
+PRL	O
+release	O
+in	O
+vitro	O
+was	O
+significantly	O
+and	O
+consistently	O
+higher	O
+than	O
+controls	O
+,	O
+after	O
+at	O
+least	O
+8	O
+days	O
+of	O
+DES	B-Chemical
+exposure	O
+.	O
+
+Beyond	O
+8	O
+days	O
+of	O
+DES	B-Chemical
+exposure	O
+,	O
+the	O
+immunochemically	O
+PRL	O
+-	O
+positive	O
+proportion	O
+of	O
+cells	O
+increased	O
+to	O
+over	O
+50	O
+%	O
+of	O
+the	O
+total	O
+population	O
+.	O
+
+Increased	O
+density	O
+and	O
+/	O
+or	O
+size	O
+and	O
+PRL	O
+content	O
+were	O
+indicated	O
+for	O
+the	O
+majority	O
+of	O
+the	O
+PRL	O
+cell	O
+population	O
+in	O
+both	O
+types	O
+of	O
+separation	O
+protocols	O
+.	O
+
+All	O
+these	O
+effects	O
+of	O
+DES	B-Chemical
+were	O
+more	O
+pronounced	O
+among	O
+previously	O
+ovariectomized	O
+animals	O
+.	O
+
+The	O
+data	O
+extend	O
+the	O
+findings	O
+of	O
+other	O
+investigators	O
+,	O
+further	O
+establishing	O
+the	O
+DES	B-Chemical
+-	O
+induced	O
+tumor	B-Disease
+as	O
+a	O
+model	O
+for	O
+study	O
+of	O
+PRL	O
+cellular	O
+control	O
+mechanisms	O
+.	O
+
+Age	O
+and	O
+renal	O
+clearance	O
+of	O
+cimetidine	B-Chemical
+.	O
+
+In	O
+35	O
+patients	O
+(	O
+ages	O
+20	O
+to	O
+86	O
+yr	O
+)	O
+receiving	O
+cimetidine	B-Chemical
+therapeutically	O
+two	O
+serum	O
+samples	O
+and	O
+all	O
+urine	O
+formed	O
+in	O
+the	O
+interim	O
+were	O
+collected	O
+for	O
+analysis	O
+of	O
+cimetidine	B-Chemical
+by	O
+high	O
+-	O
+pressure	O
+liquid	O
+chromatography	O
+and	O
+for	O
+creatinine	B-Chemical
+.	O
+
+Cimetidine	B-Chemical
+clearance	O
+decreased	O
+with	O
+age	O
+.	O
+
+The	O
+extrapolated	O
+6	O
+-	O
+hr	O
+serum	O
+concentration	O
+of	O
+cimetidine	B-Chemical
+per	O
+unit	O
+dose	O
+,	O
+after	O
+intravenous	O
+cimetidine	B-Chemical
+,	O
+increased	O
+with	O
+age	O
+of	O
+the	O
+patients	O
+.	O
+
+The	O
+ratio	O
+of	O
+cimetidine	B-Chemical
+clearance	O
+to	O
+creatinine	B-Chemical
+clearance	O
+(	O
+Rc	O
+)	O
+averaged	O
+4	O
+.	O
+8	O
++	O
+/	O
+-	O
+2	O
+.	O
+0	O
+,	O
+indicating	O
+net	O
+tubular	O
+secretion	O
+for	O
+cimetidine	B-Chemical
+.	O
+
+Rc	O
+seemed	O
+to	O
+be	O
+independent	O
+of	O
+age	O
+and	O
+decreased	O
+with	O
+increasing	O
+serum	O
+concentration	O
+of	O
+cimetidine	B-Chemical
+,	O
+suggesting	O
+that	O
+secretion	O
+of	O
+cimetidine	B-Chemical
+is	O
+a	O
+saturable	O
+process	O
+.	O
+
+There	O
+was	O
+only	O
+one	O
+case	O
+of	O
+dementia	B-Disease
+possibly	O
+due	O
+to	O
+cimetidine	B-Chemical
+(	O
+with	O
+a	O
+drug	O
+level	O
+of	O
+1	O
+.	O
+9	O
+microgram	O
+/	O
+ml	O
+6	O
+hr	O
+after	O
+a	O
+dose	O
+)	O
+in	O
+a	O
+group	O
+of	O
+13	O
+patients	O
+without	O
+liver	B-Disease
+or	I-Disease
+kidney	I-Disease
+disease	I-Disease
+who	O
+had	O
+cimetidine	B-Chemical
+levels	O
+above	O
+1	O
+.	O
+25	O
+microgram	O
+/	O
+ml	O
+.	O
+
+Thus	O
+,	O
+high	O
+cimetidine	B-Chemical
+levels	O
+alone	O
+do	O
+not	O
+always	O
+induce	O
+dementia	B-Disease
+.	O
+
+Further	O
+observations	O
+on	O
+the	O
+electrophysiologic	O
+effects	O
+of	O
+oral	O
+amiodarone	B-Chemical
+therapy	O
+.	O
+
+A	O
+case	O
+is	O
+presented	O
+of	O
+a	O
+reversible	O
+intra	B-Disease
+-	I-Disease
+Hisian	I-Disease
+block	I-Disease
+occurring	O
+under	O
+amiodarone	B-Chemical
+treatment	O
+for	O
+atrial	B-Disease
+tachycardia	I-Disease
+in	O
+a	O
+patient	O
+without	O
+clear	O
+intraventricular	B-Disease
+conduction	I-Disease
+abnormalities	I-Disease
+.	O
+
+His	O
+bundle	O
+recordings	O
+showed	O
+an	O
+atrial	B-Disease
+tachycardia	I-Disease
+with	O
+intermittent	O
+exit	O
+block	O
+and	O
+greatly	O
+prolonged	O
+BH	O
+and	O
+HV	O
+intervals	O
+(	O
+40	O
+and	O
+100	O
+msec	O
+,	O
+respectively	O
+)	O
+.	O
+
+Thirty	O
+days	O
+after	O
+amiodarone	B-Chemical
+discontinuation	O
+,	O
+His	O
+bundle	O
+electrograms	O
+showed	O
+atrial	B-Disease
+flutter	I-Disease
+without	O
+intra	O
+-	O
+Hisian	O
+or	O
+infra	O
+-	O
+Hisian	O
+delay	O
+.	O
+
+Amiodarone	B-Chemical
+should	O
+be	O
+used	O
+with	O
+caution	O
+during	O
+long	O
+-	O
+term	O
+oral	O
+therapy	O
+in	O
+patients	O
+with	O
+or	O
+without	O
+clear	O
+intraventricular	O
+conduction	O
+defects	O
+.	O
+
+Development	O
+of	O
+clear	B-Disease
+cell	I-Disease
+adenocarcinoma	I-Disease
+in	O
+DES	B-Chemical
+-	O
+exposed	O
+offspring	O
+under	O
+observation	O
+.	O
+
+Two	O
+cases	O
+of	O
+clear	B-Disease
+cell	I-Disease
+adenocarcinoma	I-Disease
+of	I-Disease
+the	I-Disease
+vagina	I-Disease
+detected	O
+at	O
+follow	O
+-	O
+up	O
+in	O
+young	O
+women	O
+exposed	O
+in	O
+utero	O
+to	O
+diethylstilbestrol	B-Chemical
+are	O
+reported	O
+.	O
+
+One	O
+patient	O
+,	O
+aged	O
+23	O
+,	O
+had	O
+been	O
+followed	O
+for	O
+2	O
+years	O
+before	O
+carcinoma	B-Disease
+was	O
+diagnosed	O
+;	O
+the	O
+second	O
+patient	O
+,	O
+aged	O
+22	O
+,	O
+had	O
+been	O
+seen	O
+on	O
+a	O
+regular	O
+basis	O
+for	O
+5	O
+years	O
+,	O
+8	O
+months	O
+.	O
+
+In	O
+both	O
+instances	O
+,	O
+suspicion	O
+of	O
+the	O
+presence	O
+of	O
+carcinoma	B-Disease
+was	O
+aroused	O
+by	O
+the	O
+palpation	O
+of	O
+a	O
+small	O
+nodule	O
+in	O
+the	O
+vaginal	O
+fornix	O
+.	O
+
+Hysterosalpingography	O
+was	O
+performed	O
+on	O
+both	O
+patients	O
+and	O
+,	O
+in	O
+1	O
+instance	O
+,	O
+an	O
+abnormal	O
+x	O
+-	O
+ray	O
+film	O
+was	O
+reflected	O
+by	O
+the	O
+gross	O
+appearance	O
+of	O
+the	O
+uterine	O
+cavity	O
+found	O
+in	O
+the	O
+surgical	O
+specimen	O
+.	O
+
+Neurologic	O
+effects	O
+of	O
+subarachnoid	O
+administration	O
+of	O
+2	B-Chemical
+-	I-Chemical
+chloroprocaine	I-Chemical
+-	I-Chemical
+CE	I-Chemical
+,	O
+bupivacaine	B-Chemical
+,	O
+and	O
+low	O
+pH	O
+normal	O
+saline	O
+in	O
+dogs	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+the	O
+neurologic	O
+consequences	O
+of	O
+deliberate	O
+subarachnoid	O
+injection	O
+of	O
+large	O
+volumes	O
+of	O
+2	B-Chemical
+-	I-Chemical
+chloroprocaine	I-Chemical
+-	I-Chemical
+CE	I-Chemical
+in	O
+experimental	O
+animals	O
+.	O
+
+The	O
+possible	O
+role	O
+of	O
+low	O
+pH	O
+as	O
+well	O
+as	O
+total	O
+volume	O
+as	O
+potential	O
+factors	O
+in	O
+causing	O
+neurotoxicity	B-Disease
+was	O
+evaluated	O
+.	O
+
+The	O
+65	O
+dogs	O
+in	O
+the	O
+study	O
+received	O
+injections	O
+in	O
+the	O
+subarachnoid	O
+space	O
+as	O
+follows	O
+:	O
+6	O
+to	O
+8	O
+ml	O
+of	O
+bupivacaine	B-Chemical
+(	O
+N	O
+=	O
+15	O
+)	O
+,	O
+2	B-Chemical
+-	I-Chemical
+chloroprocaine	I-Chemical
+-	I-Chemical
+CE	I-Chemical
+(	O
+N	O
+=	O
+20	O
+)	O
+,	O
+low	O
+pH	O
+normal	O
+saline	O
+(	O
+pH	O
+3	O
+.	O
+0	O
+)	O
+(	O
+N	O
+=	O
+20	O
+)	O
+,	O
+or	O
+normal	O
+saline	O
+(	O
+N	O
+=	O
+10	O
+)	O
+.	O
+
+Of	O
+the	O
+20	O
+animals	O
+that	O
+received	O
+subarachnoid	O
+injection	O
+of	O
+2	B-Chemical
+-	I-Chemical
+chloroprocaine	I-Chemical
+-	I-Chemical
+CE	I-Chemical
+seven	O
+(	O
+35	O
+%	O
+)	O
+developed	O
+hind	O
+-	O
+limb	O
+paralysis	B-Disease
+.	O
+
+None	O
+of	O
+the	O
+animals	O
+that	O
+received	O
+bupivacaine	B-Chemical
+,	O
+normal	O
+saline	O
+,	O
+or	O
+normal	O
+saline	O
+titrated	O
+to	O
+a	O
+pH	O
+3	O
+.	O
+0	O
+developed	O
+hind	O
+-	O
+limb	O
+paralysis	B-Disease
+.	O
+
+Of	O
+the	O
+15	O
+spinal	O
+cords	O
+of	O
+the	O
+animals	O
+that	O
+received	O
+2	B-Chemical
+-	I-Chemical
+chloroprocaine	I-Chemical
+-	I-Chemical
+CE	I-Chemical
+,	O
+13	O
+showed	O
+subpial	B-Disease
+necrosis	I-Disease
+;	O
+the	O
+nerve	O
+roots	O
+and	O
+subarachnoid	O
+vessels	O
+were	O
+normal	O
+.	O
+
+The	O
+spinal	O
+cords	O
+of	O
+the	O
+animals	O
+that	O
+received	O
+bupivacaine	B-Chemical
+,	O
+low	O
+pH	O
+normal	O
+saline	O
+(	O
+pH	O
+3	O
+.	O
+0	O
+)	O
+,	O
+or	O
+normal	O
+saline	O
+did	O
+not	O
+show	O
+abnormal	O
+findings	O
+.	O
+
+Procainamide	B-Chemical
+-	O
+induced	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+Seven	O
+cases	O
+of	O
+procainamide	B-Chemical
+-	O
+induced	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+are	O
+presented	O
+.	O
+
+In	O
+four	O
+patients	O
+,	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+appeared	O
+after	O
+intravenous	O
+administration	O
+of	O
+200	O
+to	O
+400	O
+mg	O
+of	O
+procainamide	B-Chemical
+for	O
+the	O
+treatment	O
+of	O
+sustained	O
+ventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+In	O
+the	O
+remaining	O
+three	O
+patients	O
+,	O
+procainamide	B-Chemical
+was	O
+administered	O
+orally	O
+for	O
+treatment	O
+of	O
+chronic	O
+premature	B-Disease
+ventricular	I-Disease
+contractions	I-Disease
+or	O
+atrial	B-Disease
+flutter	I-Disease
+.	O
+
+These	O
+patients	O
+had	O
+Q	B-Disease
+-	I-Disease
+T	I-Disease
+prolongation	I-Disease
+and	O
+recurrent	O
+syncope	B-Disease
+due	O
+to	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+In	O
+four	O
+patients	O
+,	O
+the	O
+arrhythmia	B-Disease
+was	O
+rapidly	O
+diagnosed	O
+and	O
+treated	O
+with	O
+disappearance	O
+of	O
+further	O
+episodes	O
+of	O
+the	O
+arrhythmia	B-Disease
+.	O
+
+In	O
+two	O
+patients	O
+,	O
+the	O
+arrhythmia	B-Disease
+degenerated	O
+into	O
+irreversible	O
+ventricular	B-Disease
+fibrillation	I-Disease
+and	O
+both	O
+patients	O
+died	O
+.	O
+
+In	O
+the	O
+seventh	O
+patient	O
+,	O
+a	O
+permanent	O
+ventricular	O
+pacemaker	O
+was	O
+inserted	O
+and	O
+,	O
+despite	O
+continuation	O
+of	O
+procainamide	B-Chemical
+therapy	O
+,	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+did	O
+not	O
+reoccur	O
+.	O
+
+These	O
+seven	O
+cases	O
+demonstrate	O
+that	O
+procainamide	B-Chemical
+can	O
+produce	O
+an	O
+acquired	O
+prolonged	B-Disease
+Q	I-Disease
+-	I-Disease
+T	I-Disease
+syndrome	I-Disease
+with	O
+polymorphous	O
+ventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+Phenobarbitone	B-Chemical
+-	O
+induced	O
+enlargement	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+in	O
+the	O
+rat	O
+:	O
+its	O
+relationship	O
+to	O
+carbon	B-Chemical
+tetrachloride	I-Chemical
+-	O
+induced	O
+cirrhosis	B-Disease
+.	O
+
+The	O
+yield	O
+of	O
+severe	O
+cirrhosis	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+(	O
+defined	O
+as	O
+a	O
+shrunken	O
+finely	O
+nodular	O
+liver	O
+with	O
+micronodular	O
+histology	O
+,	O
+ascites	B-Disease
+greater	O
+than	O
+30	O
+ml	O
+,	O
+plasma	O
+albumin	O
+less	O
+than	O
+2	O
+.	O
+2	O
+g	O
+/	O
+dl	O
+,	O
+splenomegaly	B-Disease
+2	O
+-	O
+3	O
+times	O
+normal	O
+,	O
+and	O
+testicular	O
+atrophy	B-Disease
+approximately	O
+half	O
+normal	O
+weight	O
+)	O
+after	O
+12	O
+doses	O
+of	O
+carbon	B-Chemical
+tetrachloride	I-Chemical
+given	O
+intragastrically	O
+in	O
+the	O
+phenobarbitone	B-Chemical
+-	O
+primed	O
+rat	O
+was	O
+increased	O
+from	O
+25	O
+%	O
+to	O
+56	O
+%	O
+by	O
+giving	O
+the	O
+initial	O
+"	O
+calibrating	O
+"	O
+dose	O
+of	O
+carbon	B-Chemical
+tetrachloride	I-Chemical
+at	O
+the	O
+peak	O
+of	O
+the	O
+phenobarbitone	B-Chemical
+-	O
+induced	O
+enlargement	B-Disease
+of	I-Disease
+the	I-Disease
+liver	I-Disease
+.	O
+
+At	O
+this	O
+point	O
+it	O
+was	O
+assumed	O
+that	O
+the	O
+cytochrome	O
+P450	O
+/	O
+CCl4	B-Chemical
+toxic	O
+state	O
+was	O
+both	O
+maximal	O
+and	O
+stable	O
+.	O
+
+The	O
+optimal	O
+rat	O
+size	O
+to	O
+begin	O
+phenobarbitone	B-Chemical
+was	O
+determined	O
+as	O
+100	O
+g	O
+,	O
+and	O
+this	O
+size	O
+as	O
+a	O
+group	O
+had	O
+a	O
+mean	O
+maximum	O
+relative	O
+liver	O
+weight	O
+increase	O
+47	O
+%	O
+greater	O
+than	O
+normal	O
+rats	O
+of	O
+the	O
+same	O
+body	O
+weight	O
+.	O
+
+The	O
+optimal	O
+time	O
+for	O
+the	O
+initial	O
+dose	O
+of	O
+carbon	B-Chemical
+tetrachloride	I-Chemical
+was	O
+after	O
+14	O
+days	O
+on	O
+phenobarbitone	B-Chemical
+.	O
+
+Triamterene	B-Chemical
+nephrolithiasis	B-Disease
+complicating	O
+dyazide	B-Chemical
+therapy	O
+.	O
+
+A	O
+case	O
+of	O
+triamterene	B-Chemical
+nephrolithiasis	B-Disease
+is	O
+reported	O
+in	O
+a	O
+man	O
+after	O
+4	O
+years	O
+of	O
+hydrochlorothiazide	B-Chemical
+-	I-Chemical
+triamterene	I-Chemical
+therapy	O
+for	O
+hypertension	B-Disease
+.	O
+
+The	O
+stone	O
+passed	O
+spontaneously	O
+and	O
+was	O
+found	O
+to	O
+contain	O
+a	O
+triamterene	B-Chemical
+metabolite	O
+admixed	O
+with	O
+uric	B-Chemical
+acid	I-Chemical
+salts	I-Chemical
+.	O
+
+Factors	O
+affecting	O
+triamterene	B-Chemical
+nephrolithiasis	B-Disease
+are	O
+discussed	O
+and	O
+2	O
+previously	O
+reported	O
+cases	O
+are	O
+reviewed	O
+.	O
+
+Busulfan	B-Chemical
+-	O
+induced	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+.	O
+
+A	O
+case	O
+of	O
+a	O
+busulfan	B-Chemical
+-	O
+induced	O
+hemorrhage	B-Disease
+cystitis	I-Disease
+is	O
+reported	O
+.	O
+
+Spontaneous	O
+resolution	O
+occurred	O
+following	O
+cessation	O
+of	O
+the	O
+drug	O
+.	O
+
+The	O
+similarity	O
+between	O
+the	O
+histologic	O
+appearances	O
+of	O
+busulfan	B-Chemical
+cystitis	B-Disease
+and	O
+both	O
+radiation	O
+and	O
+cyclophosphamide	B-Chemical
+-	O
+induced	O
+cystitis	B-Disease
+is	O
+discussed	O
+and	O
+the	O
+world	O
+literature	O
+reviewed	O
+.	O
+
+In	O
+view	O
+of	O
+the	O
+known	O
+tendency	O
+of	O
+busulfan	B-Chemical
+to	O
+induce	O
+cellular	O
+atypia	O
+and	O
+carcinoma	B-Disease
+in	O
+other	O
+sites	O
+,	O
+periodic	O
+urinary	O
+cytology	O
+is	O
+suggested	O
+in	O
+patients	O
+on	O
+long	O
+-	O
+term	O
+therapy	O
+.	O
+
+Variant	O
+ventricular	B-Disease
+tachycardia	I-Disease
+in	O
+desipramine	B-Chemical
+toxicity	B-Disease
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+variant	O
+ventricular	B-Disease
+tachycardia	I-Disease
+induced	O
+by	O
+desipramine	B-Chemical
+toxicity	B-Disease
+.	O
+
+Unusual	O
+features	O
+of	O
+the	O
+arrhythmia	B-Disease
+are	O
+repetitive	O
+group	O
+beating	O
+,	O
+progressive	O
+shortening	O
+of	O
+the	O
+R	O
+-	O
+R	O
+interval	O
+,	O
+progressive	O
+widening	O
+of	O
+the	O
+QRS	O
+complex	O
+with	O
+eventual	O
+failure	O
+of	O
+intraventricular	O
+conduction	O
+,	O
+and	O
+changes	O
+in	O
+direction	O
+of	O
+the	O
+QRS	O
+axis	O
+.	O
+
+Recognition	O
+of	O
+variant	O
+ventricular	B-Disease
+tachycardia	I-Disease
+is	O
+important	O
+because	O
+therapy	O
+differs	O
+from	O
+that	O
+of	O
+classic	O
+ventricular	B-Disease
+tachycardia	I-Disease
+.	O
+
+Rebound	O
+hypertensive	B-Disease
+after	O
+sodium	B-Chemical
+nitroprusside	I-Chemical
+prevented	O
+by	O
+saralasin	B-Chemical
+in	O
+rats	O
+.	O
+
+The	O
+role	O
+of	O
+the	O
+renin	O
+-	O
+-	O
+angiotensin	B-Chemical
+system	O
+in	O
+the	O
+maintenance	O
+of	O
+blood	O
+pressure	O
+during	O
+halothane	B-Chemical
+anesthesia	O
+and	O
+sodium	B-Chemical
+nitroprusside	I-Chemical
+(	O
+SNP	B-Chemical
+)	O
+-	O
+induced	O
+hypotension	B-Disease
+was	O
+evaluated	O
+.	O
+
+Control	O
+rats	O
+received	O
+halothane	B-Chemical
+anesthesia	O
+(	O
+1	O
+MAC	O
+)	O
+for	O
+one	O
+hour	O
+,	O
+followed	O
+by	O
+SNP	B-Chemical
+infusion	O
+,	O
+40	O
+microgram	O
+/	O
+kg	O
+/	O
+min	O
+,	O
+for	O
+30	O
+min	O
+,	O
+followed	O
+by	O
+a	O
+30	O
+-	O
+min	O
+recovery	O
+period	O
+.	O
+
+A	O
+second	O
+group	O
+of	O
+rats	O
+was	O
+treated	O
+identically	O
+and	O
+,	O
+in	O
+addition	O
+,	O
+received	O
+an	O
+infusion	O
+of	O
+saralasin	B-Chemical
+(	O
+a	O
+competitive	O
+inhibitor	O
+of	O
+angiotensin	B-Chemical
+II	I-Chemical
+)	O
+throughout	O
+the	O
+experimental	O
+period	O
+.	O
+
+In	O
+each	O
+group	O
+,	O
+SNP	B-Chemical
+infusion	O
+resulted	O
+in	O
+an	O
+initial	O
+decrease	O
+in	O
+blood	O
+pressure	O
+from	O
+86	O
+torr	O
+and	O
+83	O
+torr	O
+,	O
+respectively	O
+,	O
+to	O
+48	O
+torr	O
+.	O
+
+During	O
+the	O
+SNP	B-Chemical
+infusion	O
+the	O
+control	O
+animals	O
+demonstrated	O
+a	O
+progressive	O
+increase	B-Disease
+in	I-Disease
+blood	I-Disease
+pressure	I-Disease
+to	O
+61	O
+torr	O
+,	O
+whereas	O
+the	O
+saralasin	B-Chemical
+-	O
+treated	O
+animals	O
+showed	O
+no	O
+change	O
+.	O
+
+Following	O
+discontinuation	O
+of	O
+SNP	B-Chemical
+,	O
+blood	O
+pressure	O
+in	O
+the	O
+control	O
+animals	O
+rebounded	O
+to	O
+94	O
+torr	O
+,	O
+as	O
+compared	O
+with	O
+78	O
+torr	O
+in	O
+the	O
+saralasin	B-Chemical
+-	O
+treated	O
+rats	O
+.	O
+
+This	O
+study	O
+indicates	O
+that	O
+with	O
+stable	O
+halothane	B-Chemical
+anesthesia	O
+,	O
+the	O
+partial	O
+recovery	O
+of	O
+blood	O
+pressure	O
+during	O
+SNP	B-Chemical
+infusion	O
+and	O
+the	O
+post	O
+-	O
+SNP	B-Chemical
+rebound	O
+of	O
+blood	O
+pressure	O
+can	O
+be	O
+completely	O
+blocked	O
+by	O
+saralasin	B-Chemical
+.	O
+
+This	O
+demonstrates	O
+the	O
+participation	O
+of	O
+the	O
+renin	O
+-	O
+-	O
+angiotensin	B-Chemical
+system	O
+in	O
+antagonizing	O
+the	O
+combined	O
+hypotensive	B-Disease
+effects	O
+of	O
+halothane	B-Chemical
+and	O
+SNP	B-Chemical
+.	O
+
+Clinical	O
+nephrotoxicity	B-Disease
+of	O
+tobramycin	B-Chemical
+and	O
+gentamicin	B-Chemical
+.	O
+
+A	O
+prospective	O
+study	O
+.	O
+
+Nearly	O
+3	O
+.	O
+2	O
+million	O
+people	O
+in	O
+this	O
+country	O
+receive	O
+aminoglycoside	B-Chemical
+antibiotics	O
+annually	O
+.	O
+
+Gentamicin	B-Chemical
+sulfate	I-Chemical
+and	O
+tobramycin	B-Chemical
+sulfate	I-Chemical
+continue	O
+to	O
+demonstrate	O
+ototoxicity	B-Disease
+and	O
+nephrotoxicity	B-Disease
+in	O
+both	O
+animal	O
+and	O
+clinical	O
+studies	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+62	O
+patients	O
+with	O
+confirmed	O
+initial	O
+normal	O
+renal	O
+function	O
+and	O
+treated	O
+with	O
+2	O
+to	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+of	O
+gentamicin	B-Chemical
+sulfate	I-Chemical
+or	O
+tobramycin	B-Chemical
+sulfate	I-Chemical
+for	O
+a	O
+minimum	O
+of	O
+seven	O
+days	O
+were	O
+followed	O
+up	O
+prospectively	O
+for	O
+the	O
+development	O
+of	O
+aminoglycoside	B-Chemical
+-	O
+related	O
+renal	B-Disease
+failure	I-Disease
+,	O
+defined	O
+as	O
+at	O
+least	O
+a	O
+one	O
+-	O
+third	O
+reduction	O
+in	O
+renal	O
+function	O
+.	O
+
+In	O
+these	O
+62	O
+patients	O
+,	O
+no	O
+other	O
+causes	O
+for	O
+renal	B-Disease
+failure	I-Disease
+could	O
+be	O
+identified	O
+.	O
+
+Five	O
+of	O
+33	O
+(	O
+15	O
+%	O
+)	O
+of	O
+the	O
+tobramycin	B-Chemical
+-	O
+treated	O
+patients	O
+and	O
+16	O
+of	O
+29	O
+(	O
+55	O
+.	O
+2	O
+%	O
+)	O
+of	O
+the	O
+gentamicin	B-Chemical
+-	O
+treated	O
+patients	O
+had	O
+renal	B-Disease
+failure	I-Disease
+.	O
+
+Thus	O
+,	O
+gentamicin	B-Chemical
+was	O
+associated	O
+with	O
+renal	B-Disease
+failure	I-Disease
+more	O
+than	O
+three	O
+times	O
+as	O
+often	O
+as	O
+was	O
+tobramycin	B-Chemical
+.	O
+
+Metabolic	O
+involvement	O
+in	O
+adriamycin	B-Chemical
+cardiotoxicity	B-Disease
+.	O
+
+The	O
+cardiotoxic	B-Disease
+effects	O
+of	O
+adriamycin	B-Chemical
+were	O
+studied	O
+in	O
+mammalian	O
+myocardial	O
+cells	O
+in	O
+culture	O
+as	O
+a	O
+model	O
+system	O
+.	O
+
+Adriamycin	B-Chemical
+inhibited	O
+cell	O
+growth	O
+and	O
+the	O
+rhythmic	O
+contractions	O
+characteristic	O
+of	O
+myocardial	O
+cells	O
+in	O
+culture	O
+.	O
+
+A	O
+possible	O
+involvement	O
+of	O
+energy	O
+metabolism	O
+was	O
+suggested	O
+previously	O
+,	O
+and	O
+in	O
+this	O
+study	O
+the	O
+adenylate	O
+energy	O
+charge	O
+and	O
+phosphorylcreatine	B-Chemical
+mole	O
+fraction	O
+were	O
+determined	O
+in	O
+the	O
+adriamycin	B-Chemical
+-	O
+treated	O
+cells	O
+.	O
+
+The	O
+adenylate	O
+energy	O
+charge	O
+was	O
+found	O
+to	O
+be	O
+significantly	O
+decreased	O
+,	O
+while	O
+the	O
+phophorylcreatine	B-Chemical
+mole	O
+fraction	O
+was	O
+unchanged	O
+.	O
+
+Such	O
+disparity	O
+suggests	O
+an	O
+inhibition	O
+of	O
+creatine	B-Chemical
+phosphokinase	O
+.	O
+
+The	O
+addition	O
+of	O
+1	O
+mM	O
+adenosine	B-Chemical
+to	O
+the	O
+myocardial	O
+cell	O
+cultures	O
+markedly	O
+increases	O
+the	O
+ATP	B-Chemical
+concentration	O
+through	O
+a	O
+pathway	O
+reportedly	O
+leading	O
+to	O
+a	O
+compartmentalized	O
+ATP	B-Chemical
+pool	O
+.	O
+
+In	O
+the	O
+adriamycin	B-Chemical
+-	O
+treated	O
+cells	O
+,	O
+the	O
+addition	O
+of	O
+adenosine	B-Chemical
+increased	O
+the	O
+adenylate	O
+charge	O
+and	O
+,	O
+concomitant	O
+with	O
+this	O
+inrcease	O
+,	O
+the	O
+cells	O
+'	O
+functional	O
+integrity	O
+,	O
+in	O
+terms	O
+of	O
+percentage	O
+of	O
+beating	O
+cells	O
+and	O
+rate	O
+of	O
+contractions	O
+,	O
+was	O
+maintained	O
+.	O
+
+Age	O
+-	O
+dependent	O
+sensitivity	O
+of	O
+the	O
+rat	O
+to	O
+neurotoxic	B-Disease
+effects	O
+of	O
+streptomycin	B-Chemical
+.	O
+
+Streptomycin	B-Chemical
+sulfate	O
+(	O
+300	O
+mg	O
+/	O
+kg	O
+s	O
+.	O
+c	O
+.	O
+)	O
+was	O
+injected	O
+for	O
+various	O
+periods	O
+into	O
+preweanling	O
+rats	O
+and	O
+for	O
+3	O
+weeks	O
+into	O
+weanling	O
+rats	O
+.	O
+
+Beginning	O
+at	O
+8	O
+days	O
+of	O
+age	O
+,	O
+body	O
+movement	O
+and	O
+hearing	O
+were	O
+examined	O
+for	O
+6	O
+and	O
+up	O
+to	O
+17	O
+weeks	O
+,	O
+respectively	O
+.	O
+
+Abnormal	B-Disease
+movements	I-Disease
+and	O
+deafness	B-Disease
+occurred	O
+only	O
+in	O
+rats	O
+treated	O
+during	O
+the	O
+preweaning	O
+period	O
+;	O
+within	O
+this	O
+period	O
+the	O
+greatest	O
+sensitivities	O
+for	O
+these	O
+abnormalities	O
+occurred	O
+from	O
+2	O
+to	O
+11	O
+-	O
+17	O
+and	O
+5	O
+to	O
+11	O
+days	O
+of	O
+age	O
+,	O
+respectively	O
+,	O
+indicating	O
+that	O
+the	O
+cochlea	O
+is	O
+more	O
+sensitive	O
+to	O
+streptomycin	B-Chemical
+than	O
+the	O
+site	O
+(	O
+vestibular	O
+or	O
+central	O
+)	O
+responsible	O
+for	O
+the	O
+dyskinesias	B-Disease
+.	O
+
+Late	O
+,	O
+late	O
+doxorubicin	B-Chemical
+cardiotoxicity	B-Disease
+.	O
+
+Cardiac	B-Disease
+toxicity	I-Disease
+is	O
+a	O
+major	O
+complication	O
+which	O
+limits	O
+the	O
+use	O
+of	O
+adriamycin	B-Chemical
+as	O
+a	O
+chemotherapeutic	O
+agent	O
+.	O
+
+Cardiomyopathy	B-Disease
+is	O
+frequent	O
+when	O
+the	O
+total	O
+dose	O
+exceeds	O
+600	O
+mg	O
+/	O
+m2	O
+and	O
+occurs	O
+within	O
+one	O
+to	O
+six	O
+months	O
+after	O
+cessation	O
+of	O
+therapy	O
+.	O
+
+A	O
+patient	O
+is	O
+reported	O
+who	O
+developed	O
+progressive	O
+cardiomyopathy	B-Disease
+two	O
+and	O
+one	O
+-	O
+half	O
+years	O
+after	O
+receiving	O
+580	O
+mg	O
+/	O
+m2	O
+which	O
+apparently	O
+represents	O
+late	O
+,	O
+late	O
+cardiotoxicity	B-Disease
+.	O
+
+Attenuation	O
+of	O
+the	O
+lithium	B-Chemical
+-	O
+induced	O
+diabetes	B-Disease
+-	I-Disease
+insipidus	I-Disease
+-	I-Disease
+like	I-Disease
+syndrome	I-Disease
+by	O
+amiloride	B-Chemical
+in	O
+rats	O
+.	O
+
+The	O
+effect	O
+of	O
+amiloride	B-Chemical
+on	O
+lithium	B-Chemical
+-	O
+induced	O
+polydipsia	B-Disease
+and	O
+polyuria	B-Disease
+and	O
+on	O
+the	O
+lithium	B-Chemical
+concentration	O
+in	O
+the	O
+plasma	O
+,	O
+brain	O
+,	O
+kidney	O
+,	O
+thyroid	O
+and	O
+red	O
+blood	O
+cells	O
+was	O
+investigated	O
+in	O
+rats	O
+,	O
+chronically	O
+treated	O
+with	O
+LiCl	B-Chemical
+.	O
+
+Amiloride	B-Chemical
+reduced	O
+the	O
+drinking	O
+and	O
+urine	O
+volume	O
+of	O
+rats	O
+in	O
+an	O
+acute	O
+(	O
+6	O
+or	O
+12	O
+h	O
+)	O
+and	O
+a	O
+subacute	O
+(	O
+3	O
+days	O
+)	O
+experiment	O
+.	O
+
+6	O
+h	O
+after	O
+the	O
+administration	O
+of	O
+amiloride	B-Chemical
+,	O
+a	O
+reduction	O
+was	O
+observed	O
+in	O
+the	O
+lithium	B-Chemical
+content	O
+of	O
+the	O
+renal	O
+medulla	O
+but	O
+not	O
+in	O
+the	O
+other	O
+organs	O
+studied	O
+.	O
+
+At	O
+12	O
+h	O
+,	O
+all	O
+the	O
+tissues	O
+showed	O
+a	O
+slight	O
+increase	O
+in	O
+lithium	B-Chemical
+levels	O
+.	O
+
+After	O
+3	O
+days	O
+of	O
+combined	O
+treatment	O
+,	O
+a	O
+marked	O
+elevation	O
+in	O
+plasma	O
+and	O
+tissue	O
+lithium	B-Chemical
+levels	O
+accompanied	O
+a	O
+reduction	O
+in	O
+water	O
+intake	O
+.	O
+
+In	O
+all	O
+the	O
+experiments	O
+,	O
+the	O
+attenuation	O
+of	O
+the	O
+lithium	B-Chemical
+-	O
+induced	O
+diabetes	B-Disease
+-	I-Disease
+insipidus	I-Disease
+-	I-Disease
+like	I-Disease
+syndrome	I-Disease
+by	O
+amiloride	B-Chemical
+was	O
+accompanied	O
+by	O
+a	O
+reduction	O
+of	O
+the	O
+ratio	O
+between	O
+the	O
+lithium	B-Chemical
+concentration	O
+in	O
+the	O
+renal	O
+medulla	O
+and	O
+its	O
+levels	O
+in	O
+the	O
+blood	O
+and	O
+an	O
+elevation	O
+in	O
+the	O
+plasma	O
+potassium	B-Chemical
+level	O
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+acute	O
+amiloride	B-Chemical
+administration	O
+to	O
+lithium	B-Chemical
+-	O
+treated	O
+patients	O
+suffering	O
+from	O
+polydipsia	B-Disease
+and	O
+polyuria	B-Disease
+might	O
+relieve	O
+these	O
+patients	O
+but	O
+prolonged	O
+amiloride	B-Chemical
+supplementation	O
+would	O
+result	O
+in	O
+elevated	O
+lithium	B-Chemical
+levels	O
+and	O
+might	O
+be	O
+hazardous	O
+.	O
+
+Cardiovascular	B-Disease
+complications	I-Disease
+associated	O
+with	O
+terbutaline	B-Chemical
+treatment	O
+for	O
+preterm	B-Disease
+labor	I-Disease
+.	O
+
+Severe	O
+cardiovascular	B-Disease
+complications	I-Disease
+occurred	O
+in	O
+eight	O
+of	O
+160	O
+patients	O
+treated	O
+with	O
+terbutaline	B-Chemical
+for	O
+preterm	B-Disease
+labor	I-Disease
+.	O
+
+Associated	O
+corticosteroid	O
+therapy	O
+and	O
+twin	O
+gestations	O
+appear	O
+to	O
+be	O
+predisposing	O
+factors	O
+.	O
+
+Potential	O
+mechanisms	O
+of	O
+the	O
+pathophysiology	O
+are	O
+briefly	O
+discussed	O
+.	O
+
+Toxic	B-Disease
+hepatitis	I-Disease
+induced	O
+by	O
+antithyroid	O
+drugs	O
+:	O
+four	O
+cases	O
+including	O
+one	O
+with	O
+cross	O
+-	O
+reactivity	O
+between	O
+carbimazole	B-Chemical
+and	O
+benzylthiouracil	B-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+This	O
+study	O
+was	O
+conducted	O
+to	O
+assess	O
+the	O
+occurrence	O
+of	O
+hepatic	B-Disease
+adverse	I-Disease
+effects	I-Disease
+encountered	O
+with	O
+antithyroid	O
+drugs	O
+.	O
+
+METHODS	O
+:	O
+Retrospective	O
+review	O
+of	O
+medical	O
+records	O
+of	O
+236	O
+patients	O
+with	O
+hyperthyroidism	B-Disease
+admitted	O
+in	O
+our	O
+department	O
+(	O
+in	O
+-	O
+or	O
+out	O
+-	O
+patients	O
+)	O
+from	O
+1986	O
+to	O
+1992	O
+.	O
+
+RESULTS	O
+:	O
+Four	O
+patients	O
+(	O
+1	O
+.	O
+7	O
+%	O
+)	O
+were	O
+identified	O
+with	O
+toxic	B-Disease
+hepatitis	I-Disease
+which	O
+could	O
+reasonably	O
+be	O
+attributed	O
+to	O
+the	O
+use	O
+of	O
+antithyroid	O
+agent	O
+.	O
+
+Two	O
+patients	O
+had	O
+a	O
+cholestatic	B-Disease
+hepatitis	I-Disease
+induced	O
+by	O
+carbimazole	B-Chemical
+(	O
+N	B-Chemical
+omercazole	I-Chemical
+)	O
+.	O
+
+Two	O
+others	O
+had	O
+a	O
+mixed	O
+(	O
+cholestatic	B-Disease
+and	O
+cytolytic	O
+)	O
+hepatitis	B-Disease
+following	O
+carbimazole	B-Chemical
+.	O
+
+One	O
+of	O
+the	O
+latter	O
+two	O
+patients	O
+further	O
+experienced	O
+a	O
+cytolytic	O
+hepatitis	B-Disease
+which	O
+appeared	O
+after	O
+Benzylthiouracil	B-Chemical
+(	O
+Basd	B-Chemical
+ne	I-Chemical
+)	O
+had	O
+replaced	O
+carbimazole	B-Chemical
+.	O
+
+Biological	O
+features	O
+of	O
+hepatitis	B-Disease
+disappeared	O
+in	O
+all	O
+cases	O
+after	O
+cessation	O
+of	O
+the	O
+incriminated	O
+drug	O
+,	O
+while	O
+biliary	O
+,	O
+viral	O
+and	O
+immunological	O
+searches	O
+were	O
+negative	O
+.	O
+
+Only	O
+2	O
+patients	O
+of	O
+our	O
+retrospective	O
+study	O
+experienced	O
+a	O
+mild	O
+or	O
+severe	O
+neutropenia	B-Disease
+.	O
+
+CONCLUSION	O
+:	O
+Toxic	B-Disease
+hepatitis	I-Disease
+is	O
+a	O
+potential	O
+adverse	O
+effect	O
+of	O
+antithyroid	O
+drugs	O
+which	O
+warrants	O
+,	O
+as	O
+for	O
+haematological	O
+disturbances	O
+,	O
+a	O
+pre	O
+-	O
+therapeutic	O
+determination	O
+and	O
+a	O
+careful	O
+follow	O
+-	O
+up	O
+of	O
+relevant	O
+biological	O
+markers	O
+.	O
+
+Moreover	O
+,	O
+hepatotoxicity	B-Disease
+may	O
+not	O
+be	O
+restricted	O
+to	O
+one	O
+class	O
+of	O
+antithyroid	O
+agents	O
+.	O
+
+Interactive	O
+effects	O
+of	O
+variations	O
+in	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+and	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+on	O
+rat	O
+atrial	O
+spontaneous	O
+frequency	O
+.	O
+
+The	O
+effects	O
+of	O
+varying	O
+the	O
+extracellular	O
+concentrations	O
+of	O
+Na	B-Chemical
+and	O
+Ca	B-Chemical
+(	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+and	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+)	O
+on	O
+both	O
+,	O
+the	O
+spontaneous	O
+beating	O
+and	O
+the	O
+negative	O
+chronotropic	O
+action	O
+of	O
+verapamil	B-Chemical
+,	O
+were	O
+studied	O
+in	O
+the	O
+isolated	O
+rat	O
+atria	O
+.	O
+
+Basal	O
+frequency	O
+(	O
+BF	O
+)	O
+evaluated	O
+by	O
+surface	O
+electrogram	O
+was	O
+223	O
++	O
+/	O
+-	O
+4	O
+beats	O
+/	O
+min	O
+.	O
+in	O
+control	O
+Krebs	O
+-	O
+Ringer	O
+containing	O
+137	O
+mM	O
+Na	B-Chemical
+and	O
+1	O
+.	O
+35	O
+mM	O
+Ca	B-Chemical
+(	O
+N	O
+)	O
+.	O
+
+It	O
+decreased	O
+by	O
+16	O
++	O
+/	O
+-	O
+3	O
+%	O
+by	O
+lowering	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+to	O
+78	O
+mM	O
+(	O
+LNa	O
+)	O
+,	O
+23	O
++	O
+/	O
+-	O
+2	O
+%	O
+by	O
+lowering	O
+simultaneously	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+to	O
+78	O
+mM	O
+and	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+to	O
+0	O
+.	O
+675	O
+mM	O
+(	O
+LNa	O
++	O
+LCa	O
+)	O
+and	O
+31	O
++	O
+/	O
+-	O
+5	O
+%	O
+by	O
+lowering	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+to	O
+78	O
+mM	O
+plus	O
+increasing	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+to	O
+3	O
+.	O
+6	O
+mM	O
+(	O
+LNa	O
++	O
+HCa	O
+)	O
+.	O
+
+At	O
+normal	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+,	O
+decrease	O
+(	O
+0	O
+.	O
+675	O
+mM	O
+)	O
+or	O
+increase	O
+(	O
+3	O
+.	O
+6	O
+mM	O
+)	O
+of	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+did	O
+not	O
+modify	O
+BF	O
+;	O
+a	O
+reduction	O
+of	O
+ten	O
+times	O
+(	O
+0	O
+.	O
+135	O
+mM	O
+of	O
+normal	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+was	O
+effective	O
+to	O
+reduce	O
+BF	O
+by	O
+40	O
++	O
+/	O
+-	O
+13	O
+%	O
+.	O
+
+All	O
+negative	O
+chronotropic	O
+effects	O
+were	O
+BF	O
+-	O
+dependent	O
+.	O
+
+Dose	O
+-	O
+dependent	O
+bradycardia	B-Disease
+induced	O
+by	O
+verapamil	B-Chemical
+was	O
+potentiated	O
+by	O
+LNa	O
+,	O
+LCa	O
+,	O
+and	O
+HCa	O
+.	O
+
+Independent	O
+but	O
+not	O
+additive	O
+effects	O
+of	O
+Na	B-Chemical
+and	O
+Ca	B-Chemical
+are	O
+shown	O
+by	O
+decreases	O
+in	O
+the	O
+values	O
+of	O
+[	O
+verapamil	B-Chemical
+]	O
+o	O
+needed	O
+to	O
+reduce	O
+BF	O
+by	O
+30	O
+%	O
+(	O
+IC30	O
+)	O
+with	O
+the	O
+following	O
+order	O
+of	O
+inhibitory	O
+potency	O
+:	O
+LNa	O
+>	O
+LCa	O
+>	O
+HCa	O
+>	O
+N	O
+,	O
+resulting	O
+LNa	O
++	O
+HCa	O
+similar	O
+to	O
+LNa	O
+.	O
+
+The	O
+[	O
+verapamil	B-Chemical
+]	O
+o	O
+that	O
+arrested	O
+atrial	O
+beating	O
+(	O
+AC	O
+)	O
+was	O
+also	O
+potentiated	O
+with	O
+the	O
+order	O
+LNa	O
+=	O
+LNa	O
++	O
+LCa	O
+=	O
+LNa	O
++	O
+HCa	O
+=	O
+LCa	O
+>	O
+HCa	O
+=	O
+N	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+rat	O
+atrial	O
+spontaneous	O
+beating	O
+is	O
+more	O
+dependent	O
+on	O
+[	O
+Na	B-Chemical
+]	O
+o	O
+than	O
+on	O
+[	O
+Ca	B-Chemical
+]	O
+o	O
+in	O
+a	O
+range	O
+of	O
++	O
+/	O
+-	O
+50	O
+%	O
+of	O
+their	O
+normal	O
+concentration	O
+.	O
+
+Also	O
+the	O
+enhancement	O
+of	O
+verapamil	B-Chemical
+effects	O
+on	O
+atrial	O
+beating	O
+was	O
+more	O
+pronounced	O
+at	O
+LNa	O
+than	O
+at	O
+LCa	O
+.	O
+(	O
+ABSTRACT	O
+TRUNCATED	O
+AT	O
+250	O
+WORDS	O
+)	O
+
+Pseudo	O
+-	O
+allergic	B-Disease
+reactions	I-Disease
+to	O
+corticosteroids	B-Chemical
+:	O
+diagnosis	O
+and	O
+alternatives	O
+.	O
+
+Two	O
+patients	O
+treated	O
+with	O
+parenteral	O
+paramethasone	B-Chemical
+(	O
+Triniol	O
+)	O
+and	O
+dexamethasone	B-Chemical
+(	O
+Sedionbel	O
+)	O
+are	O
+described	O
+.	O
+
+A	O
+few	O
+minutes	O
+after	O
+administration	O
+of	O
+the	O
+drugs	O
+,	O
+they	O
+presented	O
+urticaria	B-Disease
+(	O
+patients	O
+1	O
+and	O
+2	O
+)	O
+and	O
+conjunctivitis	B-Disease
+(	O
+patient	O
+1	O
+)	O
+.	O
+
+The	O
+purpose	O
+of	O
+our	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+cause	O
+of	O
+the	O
+patients	O
+'	O
+reactions	O
+,	O
+the	O
+immunological	O
+mechanisms	O
+involved	O
+and	O
+whether	O
+these	O
+patients	O
+would	O
+be	O
+able	O
+to	O
+tolerate	O
+any	O
+kind	O
+of	O
+corticoid	O
+.	O
+
+Clinical	O
+examinations	O
+and	O
+skin	O
+,	O
+oral	O
+and	O
+parenteral	O
+challenges	O
+with	O
+different	O
+corticosteroids	B-Chemical
+and	O
+ELISA	O
+tests	O
+were	O
+performed	O
+.	O
+
+In	O
+the	O
+two	O
+patients	O
+,	O
+skin	O
+and	O
+ELISA	O
+tests	O
+with	O
+paramethasone	B-Chemical
+were	O
+negative	O
+,	O
+as	O
+was	O
+the	O
+prick	O
+test	O
+with	O
+each	O
+of	O
+its	O
+excipients	O
+.	O
+
+A	O
+single	O
+-	O
+blind	O
+parenteral	O
+challenge	O
+with	O
+Triniol	O
+was	O
+positive	O
+in	O
+both	O
+patients	O
+after	O
+the	O
+administration	O
+of	O
+1	O
+ml	O
+of	O
+the	O
+drug	O
+,	O
+and	O
+negative	O
+with	O
+its	O
+excipients	O
+.	O
+
+We	O
+also	O
+carried	O
+out	O
+oral	O
+and	O
+parenteral	O
+challenges	O
+with	O
+other	O
+corticosteroids	B-Chemical
+and	O
+found	O
+intolerance	O
+to	O
+some	O
+of	O
+them	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+paramethasone	B-Chemical
+caused	O
+pseudoallergic	O
+reactions	O
+in	O
+our	O
+patients	O
+.	O
+
+Corticosteroids	O
+different	O
+from	O
+paramethasone	B-Chemical
+also	O
+produced	O
+hypersensitivity	B-Disease
+reactions	O
+in	O
+these	O
+patients	O
+;	O
+however	O
+,	O
+a	O
+few	O
+of	O
+them	O
+were	O
+tolerated	O
+.	O
+
+The	O
+basic	O
+mechanisms	O
+of	O
+those	O
+reactions	O
+are	O
+not	O
+yet	O
+fully	O
+understood	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+report	O
+of	O
+a	O
+pseudo	O
+-	O
+allergy	B-Disease
+caused	O
+by	O
+paramethasone	B-Chemical
+.	O
+
+Study	O
+of	O
+the	O
+role	O
+of	O
+vitamin	B-Chemical
+B12	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+supplementation	O
+in	O
+preventing	O
+hematologic	O
+toxicity	B-Disease
+of	O
+zidovudine	B-Chemical
+.	O
+
+A	O
+prospective	O
+,	O
+randomized	O
+study	O
+was	O
+conducted	O
+to	O
+evaluate	O
+the	O
+role	O
+of	O
+vitamin	B-Chemical
+B12	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+supplementation	O
+in	O
+preventing	O
+zidovudine	B-Chemical
+(	O
+ZDV	B-Chemical
+)	O
+-	O
+induced	O
+bone	B-Disease
+marrow	I-Disease
+suppression	I-Disease
+.	O
+
+Seventy	O
+-	O
+five	O
+human	B-Disease
+immunodeficiency	I-Disease
+virus	I-Disease
+(	I-Disease
+HIV	I-Disease
+)	I-Disease
+-	I-Disease
+infected	I-Disease
+patients	O
+with	O
+CD4	O
++	O
+cell	O
+counts	O
+<	O
+500	O
+/	O
+mm3	O
+were	O
+randomized	O
+to	O
+receive	O
+either	O
+ZDV	B-Chemical
+(	O
+500	O
+mg	O
+daily	O
+)	O
+alone	O
+(	O
+group	O
+I	O
+,	O
+n	O
+=	O
+38	O
+)	O
+or	O
+in	O
+combination	O
+with	O
+folinic	B-Chemical
+acid	I-Chemical
+(	O
+15	O
+mg	O
+daily	O
+)	O
+and	O
+intramascular	O
+vitamin	B-Chemical
+B12	I-Chemical
+(	O
+1000	O
+micrograms	O
+monthly	O
+)	O
+(	O
+group	O
+II	O
+,	O
+n	O
+=	O
+37	O
+)	O
+.	O
+
+Finally	O
+,	O
+15	O
+patients	O
+were	O
+excluded	O
+from	O
+the	O
+study	O
+(	O
+noncompliance	O
+14	O
+,	O
+death	B-Disease
+1	O
+)	O
+;	O
+thus	O
+,	O
+60	O
+patients	O
+(	O
+31	O
+in	O
+group	O
+I	O
+and	O
+29	O
+in	O
+group	O
+II	O
+)	O
+were	O
+eligible	O
+for	O
+analysis	O
+.	O
+
+No	O
+significant	O
+differences	O
+between	O
+groups	O
+were	O
+found	O
+at	O
+enrollment	O
+.	O
+
+During	O
+the	O
+study	O
+,	O
+vitamin	B-Chemical
+B12	I-Chemical
+and	O
+folate	B-Chemical
+levels	O
+were	O
+significantly	O
+higher	O
+in	O
+group	O
+II	O
+patients	O
+;	O
+however	O
+,	O
+no	O
+differences	O
+in	O
+hemoglobin	O
+,	O
+hematocrit	O
+,	O
+mean	O
+corpuscular	O
+volume	O
+,	O
+and	O
+white	O
+-	O
+cell	O
+,	O
+neutrophil	O
+and	O
+platelet	O
+counts	O
+were	O
+observed	O
+between	O
+groups	O
+at	O
+3	O
+,	O
+6	O
+,	O
+9	O
+and	O
+12	O
+months	O
+.	O
+
+Severe	O
+hematologic	O
+toxicity	B-Disease
+(	O
+neutrophil	O
+count	O
+<	O
+1000	O
+/	O
+mm3	O
+and	O
+/	O
+or	O
+hemoglobin	O
+<	O
+8	O
+g	O
+/	O
+dl	O
+)	O
+occurred	O
+in	O
+4	O
+patients	O
+assigned	O
+to	O
+group	O
+I	O
+and	O
+7	O
+assigned	O
+to	O
+group	O
+II	O
+.	O
+
+There	O
+was	O
+no	O
+correlation	O
+between	O
+vitamin	B-Chemical
+B12	I-Chemical
+or	O
+folate	B-Chemical
+levels	O
+and	O
+development	O
+of	O
+myelosuppression	B-Disease
+.	O
+
+Vitamin	B-Chemical
+B12	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+supplementation	O
+of	O
+ZDV	B-Chemical
+therapy	O
+does	O
+not	O
+seem	O
+useful	O
+in	O
+preventing	O
+or	O
+reducing	O
+ZDV	B-Chemical
+-	O
+induced	O
+myelotoxicity	B-Disease
+in	O
+the	O
+overall	O
+treated	O
+population	O
+,	O
+although	O
+a	O
+beneficial	O
+effect	O
+in	O
+certain	O
+subgroups	O
+of	O
+patients	O
+cannot	O
+be	O
+excluded	O
+.	O
+
+Safety	O
+and	O
+side	O
+-	O
+effects	O
+of	O
+alprazolam	B-Chemical
+.	O
+
+Controlled	O
+study	O
+in	O
+agoraphobia	B-Disease
+with	O
+panic	B-Disease
+disorder	I-Disease
+.	O
+
+BACKGROUND	O
+:	O
+The	O
+widespread	O
+use	O
+of	O
+benzodiazepines	B-Chemical
+has	O
+led	O
+to	O
+increasing	O
+recognition	O
+of	O
+their	O
+unwanted	O
+effects	O
+.	O
+
+The	O
+efficacy	O
+of	O
+alprazolam	B-Chemical
+and	O
+placebo	O
+in	O
+panic	B-Disease
+disorder	I-Disease
+with	O
+agoraphobia	B-Disease
+,	O
+and	O
+the	O
+side	O
+-	O
+effect	O
+and	O
+adverse	O
+effect	O
+profiles	O
+of	O
+both	O
+drug	O
+groups	O
+were	O
+measured	O
+.	O
+
+METHOD	O
+:	O
+In	O
+London	O
+and	O
+Toronto	O
+154	O
+patients	O
+who	O
+met	O
+DSM	O
+-	O
+III	O
+criteria	O
+for	O
+panic	B-Disease
+disorder	I-Disease
+with	O
+agoraphobia	B-Disease
+were	O
+randomised	O
+to	O
+alprazolam	B-Chemical
+or	O
+placebo	O
+.	O
+
+Subjects	O
+in	O
+each	O
+drug	O
+group	O
+also	O
+received	O
+either	O
+exposure	O
+or	O
+relaxation	O
+.	O
+
+Treatment	O
+was	O
+from	O
+weeks	O
+0	O
+to	O
+8	O
+and	O
+was	O
+then	O
+tapered	O
+from	O
+weeks	O
+8	O
+to	O
+16	O
+.	O
+
+RESULTS	O
+:	O
+Mean	O
+alprazolam	B-Chemical
+dose	O
+was	O
+5	O
+mg	O
+daily	O
+.	O
+
+Compared	O
+with	O
+placebo	O
+subjects	O
+,	O
+alprazolam	B-Chemical
+patients	O
+developed	O
+more	O
+adverse	O
+reactions	O
+(	O
+21	O
+%	O
+v	O
+.	O
+0	O
+%	O
+)	O
+of	O
+depression	B-Disease
+,	O
+enuresis	B-Disease
+,	O
+disinhibition	O
+and	O
+aggression	B-Disease
+;	O
+and	O
+more	O
+side	O
+-	O
+effects	O
+,	O
+particularly	O
+sedation	O
+,	O
+irritability	B-Disease
+,	O
+impaired	B-Disease
+memory	I-Disease
+,	O
+weight	B-Disease
+loss	I-Disease
+and	O
+ataxia	B-Disease
+.	O
+
+Side	O
+-	O
+effects	O
+tended	O
+to	O
+diminish	O
+during	O
+treatment	O
+but	O
+remained	O
+significant	O
+at	O
+week	O
+8	O
+.	O
+
+Despite	O
+this	O
+,	O
+the	O
+drop	O
+-	O
+out	O
+rate	O
+was	O
+low	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Alprazolam	B-Chemical
+caused	O
+side	O
+-	O
+effects	O
+and	O
+adverse	O
+effects	O
+during	O
+treatment	O
+but	O
+many	O
+patients	O
+were	O
+willing	O
+to	O
+accept	O
+these	O
+.	O
+
+Crescentic	O
+fibrillary	O
+glomerulonephritis	B-Disease
+associated	O
+with	O
+intermittent	O
+rifampin	B-Chemical
+therapy	O
+for	O
+pulmonary	B-Disease
+tuberculosis	I-Disease
+.	O
+
+This	O
+case	O
+study	O
+reveals	O
+an	O
+unusual	O
+finding	O
+of	O
+rapidly	O
+proliferative	O
+crescentic	O
+glomerulonephritis	B-Disease
+in	O
+a	O
+patient	O
+treated	O
+with	O
+rifampin	B-Chemical
+who	O
+had	O
+no	O
+other	O
+identifiable	O
+causes	O
+for	O
+developing	O
+this	O
+disease	O
+.	O
+
+This	O
+patient	O
+underwent	O
+a	O
+10	O
+-	O
+month	O
+regimen	O
+of	O
+rifampin	B-Chemical
+and	O
+isoniazid	B-Chemical
+for	O
+pulmonary	B-Disease
+tuberculosis	I-Disease
+and	O
+was	O
+discovered	O
+to	O
+have	O
+developed	O
+signs	O
+of	O
+severe	O
+renal	B-Disease
+failure	I-Disease
+five	O
+weeks	O
+after	O
+completion	O
+of	O
+therapy	O
+.	O
+
+Renal	O
+biopsy	O
+revealed	O
+severe	O
+glomerulonephritis	B-Disease
+with	O
+crescents	O
+,	O
+electron	O
+dense	O
+fibrillar	O
+deposits	O
+and	O
+moderate	O
+lymphocytic	O
+interstitial	O
+infiltrate	O
+.	O
+
+Other	O
+possible	O
+causes	O
+of	O
+rapidly	O
+progressive	O
+glomerulonephritis	B-Disease
+were	O
+investigated	O
+and	O
+ruled	O
+out	O
+.	O
+
+This	O
+report	O
+documents	O
+the	O
+unusual	O
+occurrence	O
+of	O
+rapidly	O
+progressive	O
+glomerulonephritis	B-Disease
+with	O
+crescents	O
+and	O
+fibrillar	O
+glomerulonephritis	B-Disease
+in	O
+a	O
+patient	O
+treated	O
+with	O
+rifampin	B-Chemical
+.	O
+
+Acute	O
+confusion	B-Disease
+induced	O
+by	O
+a	O
+high	O
+-	O
+dose	O
+infusion	O
+of	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+.	O
+
+A	O
+61	O
+-	O
+year	O
+-	O
+old	O
+man	O
+was	O
+treated	O
+with	O
+combination	O
+chemotherapy	O
+incorporating	O
+cisplatinum	B-Chemical
+,	O
+etoposide	B-Chemical
+,	O
+high	O
+-	O
+dose	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+(	O
+2	O
+,	O
+250	O
+mg	O
+/	O
+m2	O
+/	O
+24	O
+hours	O
+)	O
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+for	O
+an	O
+inoperable	O
+gastric	B-Disease
+adenocarcinoma	I-Disease
+.	O
+
+He	O
+developed	O
+acute	O
+neurologic	O
+symptoms	O
+of	O
+mental	O
+confusion	B-Disease
+,	O
+disorientation	B-Disease
+and	O
+irritability	B-Disease
+,	O
+and	O
+then	O
+lapsed	O
+into	O
+a	O
+deep	O
+coma	B-Disease
+,	O
+lasting	O
+for	O
+approximately	O
+40	O
+hours	O
+during	O
+the	O
+first	O
+dose	O
+(	O
+day	O
+2	O
+)	O
+of	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+infusion	O
+.	O
+
+This	O
+complication	O
+reappeared	O
+on	O
+day	O
+25	O
+during	O
+the	O
+second	O
+dose	O
+of	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+and	O
+folinic	B-Chemical
+acid	I-Chemical
+,	O
+which	O
+were	O
+then	O
+the	O
+only	O
+drugs	O
+given	O
+.	O
+
+Because	O
+folinic	B-Chemical
+acid	I-Chemical
+was	O
+unlikely	O
+to	O
+be	O
+associated	O
+with	O
+this	O
+condition	O
+,	O
+neurotoxicity	B-Disease
+due	O
+to	O
+high	O
+-	O
+dose	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+was	O
+highly	O
+suspected	O
+.	O
+
+The	O
+pathogenesis	O
+of	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+neurotoxicity	B-Disease
+may	O
+be	O
+due	O
+to	O
+a	O
+Krebs	O
+cycle	O
+blockade	O
+by	O
+fluoroacetate	B-Chemical
+and	O
+fluorocitrate	B-Chemical
+,	O
+thiamine	B-Chemical
+deficiency	O
+,	O
+or	O
+dihydrouracil	B-Chemical
+dehydrogenase	O
+deficiency	O
+.	O
+
+High	O
+-	O
+dose	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+/	O
+folinic	B-Chemical
+acid	I-Chemical
+infusion	O
+therapy	O
+has	O
+recently	O
+become	O
+a	O
+popular	O
+regimen	O
+for	O
+various	O
+cancers	B-Disease
+.	O
+
+It	O
+is	O
+necessary	O
+that	O
+both	O
+oncologists	O
+and	O
+neurologists	O
+be	O
+fully	O
+aware	O
+of	O
+this	O
+unusual	O
+complication	O
+.	O
+
+Effect	O
+of	O
+switching	O
+carbamazepine	B-Chemical
+to	O
+oxcarbazepine	B-Chemical
+on	O
+the	O
+plasma	O
+levels	O
+of	O
+neuroleptics	O
+.	O
+
+A	O
+case	O
+report	O
+.	O
+
+Carbamazepine	B-Chemical
+was	O
+switched	O
+to	O
+its	O
+10	O
+-	O
+keto	O
+analogue	O
+oxcarbazepine	B-Chemical
+among	O
+six	O
+difficult	O
+-	O
+to	O
+-	O
+treat	O
+schizophrenic	B-Disease
+or	O
+organic	B-Disease
+psychotic	I-Disease
+patients	O
+using	O
+concomitantly	O
+haloperidol	B-Chemical
+,	O
+chlorpromazine	B-Chemical
+or	O
+clozapine	B-Chemical
+.	O
+
+This	O
+change	O
+resulted	O
+within	O
+2	O
+-	O
+4	O
+weeks	O
+in	O
+the	O
+50	O
+-	O
+200	O
+%	O
+increase	O
+in	O
+the	O
+plasma	O
+levels	O
+of	O
+these	O
+neuroleptics	O
+and	O
+the	O
+appearance	O
+of	O
+extrapyramidal	B-Disease
+symptoms	I-Disease
+.	O
+
+None	O
+of	O
+the	O
+patients	O
+showed	O
+any	O
+clinical	O
+deteriotation	O
+during	O
+the	O
+following	O
+3	O
+-	O
+6	O
+months	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+case	O
+report	O
+support	O
+the	O
+idea	O
+that	O
+in	O
+contrast	O
+with	O
+carbamazepine	B-Chemical
+oxcarbazepine	B-Chemical
+does	O
+not	O
+induce	O
+the	O
+hepatic	O
+microsomal	O
+enzyme	O
+systems	O
+regulating	O
+the	O
+inactivation	O
+of	O
+antipsychotic	O
+drugs	O
+.	O
+
+Time	O
+course	O
+of	O
+lipid	O
+peroxidation	O
+in	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+-	O
+induced	O
+nephropathy	B-Disease
+.	O
+
+Reactive	O
+oxygen	B-Chemical
+species	O
+have	O
+been	O
+implicated	O
+in	O
+the	O
+pathogenesis	O
+of	O
+acute	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+(	O
+PAN	B-Chemical
+)	O
+-	O
+induced	O
+nephropathy	B-Disease
+,	O
+with	O
+antioxidants	O
+significantly	O
+reducing	O
+the	O
+proteinuria	B-Disease
+.	O
+
+The	O
+temporal	O
+relationship	O
+between	O
+lipid	O
+peroxidation	O
+in	O
+the	O
+kidney	O
+and	O
+proteinuria	B-Disease
+was	O
+examined	O
+in	O
+this	O
+study	O
+.	O
+
+Rats	O
+were	O
+treated	O
+with	O
+a	O
+single	O
+IV	O
+injection	O
+of	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+,	O
+(	O
+PAN	B-Chemical
+,	O
+7	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+)	O
+and	O
+24	O
+hour	O
+urine	O
+samples	O
+were	O
+obtained	O
+prior	O
+to	O
+sacrifice	O
+on	O
+days	O
+3	O
+,	O
+5	O
+,	O
+7	O
+,	O
+10	O
+,	O
+17	O
+,	O
+27	O
+,	O
+41	O
+(	O
+N	O
+=	O
+5	O
+-	O
+10	O
+per	O
+group	O
+)	O
+.	O
+
+The	O
+kidneys	O
+were	O
+removed	O
+,	O
+flushed	O
+with	O
+ice	O
+cold	O
+TRIS	O
+buffer	O
+.	O
+
+Kidney	O
+cortices	O
+from	O
+each	O
+animal	O
+were	O
+used	O
+to	O
+prepare	O
+homogenates	O
+.	O
+
+Tissue	O
+lipid	O
+peroxidation	O
+was	O
+measured	O
+in	O
+whole	O
+homogenates	O
+as	O
+well	O
+as	O
+in	O
+lipid	O
+extracts	O
+from	O
+homogenates	O
+as	O
+thiobarbituric	B-Chemical
+acid	I-Chemical
+reactive	O
+substances	O
+.	O
+
+Proteinuria	B-Disease
+was	O
+evident	O
+at	O
+day	O
+5	O
+,	O
+peaked	O
+at	O
+day	O
+7	O
+and	O
+persisted	O
+to	O
+day	O
+27	O
+.	O
+
+Lipid	O
+peroxidation	O
+in	O
+homogenates	O
+was	O
+maximal	O
+at	O
+day	O
+3	O
+and	O
+declined	O
+rapidly	O
+to	O
+control	O
+levels	O
+by	O
+day	O
+17	O
+.	O
+
+This	O
+study	O
+supports	O
+the	O
+role	O
+of	O
+lipid	O
+peroxidation	O
+in	O
+mediating	O
+the	O
+proteinuric	B-Disease
+injury	I-Disease
+in	O
+PAN	B-Chemical
+nephropathy	B-Disease
+.	O
+
+Composition	O
+of	O
+gall	B-Disease
+bladder	I-Disease
+stones	I-Disease
+associated	O
+with	O
+octreotide	B-Chemical
+:	O
+response	O
+to	O
+oral	O
+ursodeoxycholic	B-Chemical
+acid	I-Chemical
+.	O
+
+Octreotide	B-Chemical
+,	O
+an	O
+effective	O
+treatment	O
+for	O
+acromegaly	B-Disease
+,	O
+induces	O
+gall	B-Disease
+bladder	I-Disease
+stones	I-Disease
+in	O
+13	O
+-	O
+60	O
+%	O
+of	O
+patients	O
+.	O
+
+Because	O
+knowledge	O
+of	O
+stone	O
+composition	O
+is	O
+essential	O
+for	O
+studies	O
+of	O
+their	O
+pathogenesis	O
+,	O
+treatment	O
+,	O
+and	O
+prevention	O
+,	O
+this	O
+was	O
+investigated	O
+by	O
+direct	O
+and	O
+indirect	O
+methods	O
+in	O
+14	O
+octreotide	B-Chemical
+treated	O
+acromegalic	B-Disease
+patients	O
+with	O
+gall	B-Disease
+stones	I-Disease
+.	O
+
+Chemical	O
+analysis	O
+of	O
+gall	B-Disease
+stones	I-Disease
+retrieved	O
+at	O
+cholecystectomy	O
+from	O
+two	O
+patients	O
+,	O
+showed	O
+that	O
+they	O
+contained	O
+71	O
+%	O
+and	O
+87	O
+%	O
+cholesterol	B-Chemical
+by	O
+weight	O
+.	O
+
+In	O
+the	O
+remaining	O
+12	O
+patients	O
+,	O
+localised	O
+computed	O
+tomography	O
+of	O
+the	O
+gall	O
+bladder	O
+showed	O
+that	O
+eight	O
+had	O
+stones	O
+with	O
+maximum	O
+attenuation	O
+scores	O
+of	O
+<	O
+100	O
+Hounsfield	O
+units	O
+(	O
+values	O
+of	O
+<	O
+100	O
+HU	O
+predict	O
+cholesterol	B-Chemical
+rich	O
+,	O
+dissolvable	O
+stones	O
+)	O
+.	O
+
+Gall	O
+bladder	O
+bile	O
+was	O
+obtained	O
+by	O
+ultrasound	O
+guided	O
+,	O
+fine	O
+needle	O
+puncture	O
+from	O
+six	O
+patients	O
+.	O
+
+All	O
+six	O
+patients	O
+had	O
+supersaturated	O
+bile	O
+(	O
+mean	O
+(	O
+SEM	O
+)	O
+cholesterol	B-Chemical
+saturation	O
+index	O
+of	O
+1	O
+.	O
+19	O
+(	O
+0	O
+.	O
+08	O
+)	O
+(	O
+range	O
+1	O
+.	O
+01	O
+-	O
+1	O
+.	O
+53	O
+)	O
+)	O
+and	O
+all	O
+had	O
+abnormally	O
+rapid	O
+cholesterol	B-Chemical
+microcrystal	O
+nucleation	O
+times	O
+(	O
+<	O
+4	O
+days	O
+(	O
+range	O
+1	O
+-	O
+4	O
+)	O
+)	O
+,	O
+whilst	O
+in	O
+four	O
+,	O
+the	O
+bile	O
+contained	O
+cholesterol	B-Chemical
+microcrystals	O
+immediately	O
+after	O
+sampling	O
+.	O
+
+Of	O
+the	O
+12	O
+patients	O
+considered	O
+for	O
+oral	O
+ursodeoxycholic	B-Chemical
+acid	I-Chemical
+(	O
+UDCA	B-Chemical
+)	O
+treatment	O
+,	O
+two	O
+had	O
+a	O
+blocked	O
+cystic	O
+duct	O
+and	O
+were	O
+not	O
+started	O
+on	O
+UDCA	B-Chemical
+while	O
+one	O
+was	O
+lost	O
+to	O
+follow	O
+up	O
+.	O
+
+After	O
+one	O
+year	O
+of	O
+treatment	O
+,	O
+five	O
+of	O
+the	O
+remaining	O
+nine	O
+patients	O
+showed	O
+either	O
+partial	O
+(	O
+n	O
+=	O
+3	O
+)	O
+or	O
+complete	O
+(	O
+n	O
+=	O
+2	O
+)	O
+gall	B-Disease
+stone	I-Disease
+dissolution	O
+,	O
+suggesting	O
+that	O
+their	O
+stones	O
+were	O
+cholesterol	B-Chemical
+rich	O
+.	O
+
+This	O
+corresponds	O
+,	O
+by	O
+actuarial	O
+(	O
+life	O
+table	O
+)	O
+analysis	O
+,	O
+to	O
+a	O
+combined	O
+gall	B-Disease
+stone	I-Disease
+dissolution	O
+rate	O
+of	O
+58	O
+.	O
+3	O
+(	O
+15	O
+.	O
+9	O
+%	O
+)	O
+.	O
+
+In	O
+conclusion	O
+,	O
+octreotide	B-Chemical
+induced	O
+gall	B-Disease
+stones	I-Disease
+are	O
+generally	O
+small	O
+,	O
+multiple	O
+,	O
+and	O
+cholesterol	B-Chemical
+rich	O
+although	O
+,	O
+in	O
+common	O
+with	O
+spontaneous	O
+gall	B-Disease
+stone	I-Disease
+disease	I-Disease
+,	O
+at	O
+presentation	O
+some	O
+patients	O
+will	O
+have	O
+a	O
+blocked	O
+cystic	O
+duct	O
+and	O
+some	O
+gall	B-Disease
+stones	I-Disease
+containing	O
+calcium	B-Chemical
+.	O
+
+Erythema	B-Disease
+multiforme	I-Disease
+and	O
+hypersensitivity	B-Disease
+myocarditis	I-Disease
+caused	O
+by	O
+ampicillin	B-Chemical
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+report	O
+a	O
+case	O
+of	O
+erythema	B-Disease
+multiforme	I-Disease
+and	O
+hypersensitivity	B-Disease
+myocarditis	I-Disease
+caused	O
+by	O
+ampicillin	B-Chemical
+.	O
+
+CASE	O
+SUMMARY	O
+:	O
+A	O
+13	O
+-	O
+year	O
+-	O
+old	O
+boy	O
+was	O
+treated	O
+with	O
+ampicillin	B-Chemical
+and	O
+gentamicin	B-Chemical
+because	O
+of	O
+suspected	O
+septicemia	B-Disease
+.	O
+
+Medications	O
+were	O
+discontinued	O
+when	O
+erythema	B-Disease
+multiforme	I-Disease
+and	O
+congestive	B-Disease
+heart	I-Disease
+failure	I-Disease
+caused	O
+by	O
+myocarditis	B-Disease
+occurred	O
+.	O
+
+The	O
+patient	O
+was	O
+treated	O
+with	O
+methylprednisolone	B-Chemical
+and	O
+gradually	O
+improved	O
+.	O
+
+Macrophage	O
+-	O
+migration	O
+inhibition	O
+(	O
+MIF	O
+)	O
+test	O
+with	O
+ampicillin	B-Chemical
+was	O
+positive	O
+.	O
+
+DISCUSSION	O
+:	O
+After	O
+most	O
+infections	B-Disease
+causing	O
+erythema	B-Disease
+multiforme	I-Disease
+and	O
+myocarditis	B-Disease
+were	O
+ruled	O
+out	O
+,	O
+a	O
+drug	B-Disease
+-	I-Disease
+induced	I-Disease
+allergic	I-Disease
+reaction	I-Disease
+was	O
+suspected	O
+.	O
+
+Positive	O
+MIF	O
+test	O
+for	O
+ampicillin	B-Chemical
+showed	O
+sensitization	O
+of	O
+the	O
+patient	O
+'	O
+s	O
+lymphocytes	O
+to	O
+ampicillin	B-Chemical
+.	O
+
+CONCLUSIONS	O
+:	O
+Hypersensitivity	B-Disease
+myocarditis	I-Disease
+is	O
+a	O
+rare	O
+and	O
+dangerous	O
+manifestation	O
+of	O
+allergy	B-Disease
+to	O
+penicillins	B-Chemical
+.	O
+
+Clomipramine	B-Chemical
+-	O
+induced	O
+sleep	B-Disease
+disturbance	I-Disease
+does	O
+not	O
+impair	O
+its	O
+prolactin	O
+-	O
+releasing	O
+action	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+undertaken	O
+to	O
+examine	O
+the	O
+role	O
+of	O
+sleep	B-Disease
+disturbance	I-Disease
+,	O
+induced	O
+by	O
+clomipramine	B-Chemical
+administration	O
+,	O
+on	O
+the	O
+secretory	O
+rate	O
+of	O
+prolactin	O
+(	O
+PRL	O
+)	O
+in	O
+addition	O
+to	O
+the	O
+direct	O
+drug	O
+effect	O
+.	O
+
+Two	O
+groups	O
+of	O
+supine	O
+subjects	O
+were	O
+studied	O
+under	O
+placebo	O
+-	O
+controlled	O
+conditions	O
+,	O
+one	O
+during	O
+the	O
+night	O
+,	O
+when	O
+sleeping	O
+(	O
+n	O
+=	O
+7	O
+)	O
+and	O
+the	O
+other	O
+at	O
+daytime	O
+,	O
+when	O
+awake	O
+(	O
+n	O
+=	O
+6	O
+)	O
+.	O
+
+Each	O
+subject	O
+received	O
+a	O
+single	O
+50	O
+mg	O
+dose	O
+of	O
+clomipramine	B-Chemical
+given	O
+orally	O
+2	O
+hours	O
+before	O
+blood	O
+collection	O
+.	O
+
+Plasma	O
+PRL	O
+concentrations	O
+were	O
+analysed	O
+at	O
+10	O
+min	O
+intervals	O
+and	O
+underlying	O
+secretory	O
+rates	O
+calculated	O
+by	O
+a	O
+deconvolution	O
+procedure	O
+.	O
+
+For	O
+both	O
+experiments	O
+the	O
+drug	O
+intake	O
+led	O
+to	O
+significant	O
+increases	O
+in	O
+PRL	O
+secretion	O
+,	O
+acting	O
+preferentially	O
+on	O
+tonic	O
+secretion	O
+as	O
+pulse	O
+amplitude	O
+and	O
+frequency	O
+did	O
+not	O
+differ	O
+significantly	O
+from	O
+corresponding	O
+control	O
+values	O
+.	O
+
+During	O
+the	O
+night	O
+clomipramine	B-Chemical
+ingestion	O
+altered	O
+the	O
+complete	O
+sleep	O
+architecture	O
+in	O
+that	O
+it	O
+suppressed	O
+REM	O
+sleep	O
+and	O
+the	O
+sleep	O
+cycles	O
+and	O
+induced	O
+increased	O
+wakefulness	O
+.	O
+
+As	O
+the	O
+relative	O
+increase	O
+in	O
+PRL	O
+secretion	O
+expressed	O
+as	O
+a	O
+percentage	O
+of	O
+the	O
+mean	O
+did	O
+not	O
+significantly	O
+differ	O
+between	O
+the	O
+night	O
+and	O
+day	O
+time	O
+studies	O
+(	O
+46	O
++	O
+/	O
+-	O
+19	O
+%	O
+vs	O
+34	O
++	O
+/	O
+-	O
+10	O
+%	O
+)	O
+,	O
+it	O
+can	O
+be	O
+concluded	O
+that	O
+the	O
+observed	O
+sleep	B-Disease
+disturbance	I-Disease
+did	O
+not	O
+interfere	O
+with	O
+the	O
+drug	O
+action	O
+per	O
+se	O
+.	O
+
+The	O
+presence	O
+of	O
+REM	O
+sleep	O
+was	O
+shown	O
+not	O
+to	O
+be	O
+a	O
+determining	O
+factor	O
+either	O
+for	O
+secretory	O
+pulse	O
+amplitude	O
+and	O
+frequency	O
+,	O
+as	O
+,	O
+for	O
+both	O
+,	O
+mean	O
+nocturnal	O
+values	O
+were	O
+similar	O
+with	O
+and	O
+without	O
+prior	O
+clomipramine	B-Chemical
+ingestion	O
+.	O
+
+Survey	O
+of	O
+complications	O
+of	O
+indocyanine	B-Chemical
+green	I-Chemical
+angiography	O
+in	O
+Japan	O
+.	O
+
+PURPOSE	O
+:	O
+We	O
+evaluated	O
+the	O
+safety	O
+of	O
+indocyanine	B-Chemical
+green	I-Chemical
+for	O
+use	O
+in	O
+fundus	O
+angiography	O
+.	O
+
+METHODS	O
+:	O
+We	O
+sent	O
+a	O
+questionnaire	O
+concerning	O
+complications	O
+of	O
+indocyanine	B-Chemical
+green	I-Chemical
+to	O
+32	O
+institutions	O
+in	O
+Japan	O
+,	O
+which	O
+were	O
+selected	O
+on	O
+the	O
+basis	O
+of	O
+the	O
+client	O
+list	O
+from	O
+the	O
+Topcon	O
+Company	O
+,	O
+which	O
+manufactures	O
+the	O
+indocyanine	B-Chemical
+green	I-Chemical
+fundus	O
+camera	O
+.	O
+
+RESULTS	O
+:	O
+Ophthalmologists	O
+at	O
+15	O
+institutions	O
+responded	O
+,	O
+reporting	O
+a	O
+total	O
+of	O
+3	O
+,	O
+774	O
+indocyanine	B-Chemical
+green	I-Chemical
+angiograms	O
+performed	O
+on	O
+2	O
+,	O
+820	O
+patients	O
+between	O
+June	O
+1984	O
+and	O
+September	O
+1992	O
+.	O
+
+Before	O
+angiography	O
+,	O
+intradermal	O
+or	O
+intravenous	O
+indocyanine	B-Chemical
+green	I-Chemical
+testing	O
+,	O
+or	O
+both	O
+was	O
+performed	O
+at	O
+13	O
+of	O
+15	O
+institutions	O
+.	O
+
+For	O
+three	O
+patients	O
+,	O
+the	O
+decision	O
+was	O
+made	O
+not	O
+to	O
+proceed	O
+with	O
+angiography	O
+after	O
+positive	O
+preangiographic	O
+testing	O
+.	O
+
+The	O
+dosage	O
+of	O
+indocyanine	B-Chemical
+green	I-Chemical
+used	O
+for	O
+angiography	O
+varied	O
+from	O
+25	O
+to	O
+75	O
+mg	O
+,	O
+depending	O
+upon	O
+the	O
+institution	O
+.	O
+
+There	O
+were	O
+13	O
+cases	O
+of	O
+adverse	O
+reactions	O
+(	O
+0	O
+.	O
+34	O
+%	O
+)	O
+,	O
+ten	O
+of	O
+which	O
+were	O
+mild	O
+reactions	O
+such	O
+as	O
+nausea	B-Disease
+,	O
+exanthema	B-Disease
+,	O
+urtication	B-Disease
+,	O
+itchiness	B-Disease
+,	O
+and	O
+urgency	O
+to	O
+defecate	O
+,	O
+and	O
+did	O
+not	O
+require	O
+treatment	O
+.	O
+
+Also	O
+recorded	O
+were	O
+one	O
+case	O
+of	O
+pain	B-Disease
+of	O
+the	O
+vein	O
+,	O
+which	O
+required	O
+treatment	O
+,	O
+and	O
+two	O
+cases	O
+of	O
+hypotension	B-Disease
+.	O
+
+The	O
+two	O
+hypotensive	B-Disease
+patients	O
+required	O
+treatment	O
+for	O
+shock	B-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+A	O
+comparison	O
+of	O
+frequency	O
+of	O
+adverse	O
+reactions	O
+to	O
+indocyanine	B-Chemical
+green	I-Chemical
+with	O
+the	O
+previously	O
+reported	O
+frequency	O
+of	O
+such	O
+reactions	O
+to	O
+fluorescein	B-Chemical
+sodium	I-Chemical
+indicated	O
+that	O
+indocyanine	B-Chemical
+green	I-Chemical
+is	O
+a	O
+safe	O
+as	O
+fluorescein	B-Chemical
+for	O
+use	O
+in	O
+angiography	O
+.	O
+
+Angioedema	B-Disease
+following	O
+the	O
+intravenous	O
+administration	O
+of	O
+metoprolol	B-Chemical
+.	O
+
+A	O
+72	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+was	O
+admitted	O
+to	O
+the	O
+hospital	O
+with	O
+"	O
+flash	O
+"	O
+pulmonary	B-Disease
+edema	I-Disease
+,	O
+preceded	O
+by	O
+chest	B-Disease
+pain	I-Disease
+,	O
+requiring	O
+intubation	O
+.	O
+
+Her	O
+medical	O
+history	O
+included	O
+coronary	B-Disease
+artery	I-Disease
+disease	I-Disease
+with	O
+previous	O
+myocardial	B-Disease
+infarctions	I-Disease
+,	O
+hypertension	B-Disease
+,	O
+and	O
+diabetes	B-Disease
+mellitus	I-Disease
+.	O
+
+A	O
+history	O
+of	O
+angioedema	B-Disease
+secondary	O
+to	O
+lisinopril	B-Chemical
+therapy	O
+was	O
+elicited	O
+.	O
+
+Current	O
+medications	O
+did	O
+not	O
+include	O
+angiotensin	B-Chemical
+-	O
+converting	O
+enzyme	O
+inhibitors	O
+or	O
+beta	O
+-	O
+blockers	O
+.	O
+
+She	O
+had	O
+no	O
+previous	O
+beta	O
+-	O
+blocking	O
+drug	O
+exposure	O
+.	O
+
+During	O
+the	O
+first	O
+day	O
+of	O
+hospitalization	O
+(	O
+while	O
+intubated	O
+)	O
+,	O
+intravenous	O
+metoprolol	B-Chemical
+was	O
+given	O
+,	O
+resulting	O
+in	O
+severe	O
+angioedema	B-Disease
+.	O
+
+The	O
+angioedema	B-Disease
+resolved	O
+after	O
+therapy	O
+with	O
+intravenous	O
+steroids	B-Chemical
+and	O
+diphenhydramine	B-Chemical
+hydrochloride	O
+.	O
+
+Effect	O
+of	O
+coniine	B-Chemical
+on	O
+the	O
+developing	O
+chick	O
+embryo	O
+.	O
+
+Coniine	B-Chemical
+,	O
+an	O
+alkaloid	O
+from	O
+Conium	O
+maculatum	O
+(	O
+poison	O
+hemlock	O
+)	O
+,	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+teratogenic	O
+in	O
+livestock	O
+.	O
+
+The	O
+major	O
+teratogenic	O
+outcome	O
+is	O
+arthrogryposis	B-Disease
+,	O
+presumably	O
+due	O
+to	O
+nicotinic	O
+receptor	O
+blockade	O
+.	O
+
+However	O
+,	O
+coniine	B-Chemical
+has	O
+failed	O
+to	O
+produce	O
+arthrogryposis	B-Disease
+in	O
+rats	O
+or	O
+mice	O
+and	O
+is	O
+only	O
+weakly	O
+teratogenic	O
+in	O
+rabbits	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+and	O
+compare	O
+the	O
+effects	O
+of	O
+coniine	B-Chemical
+and	O
+nicotine	B-Chemical
+in	O
+the	O
+developing	O
+chick	O
+.	O
+
+Concentrations	O
+of	O
+coniine	B-Chemical
+and	O
+nicotine	B-Chemical
+sulfate	O
+were	O
+0	O
+.	O
+015	O
+%	O
+,	O
+0	O
+.	O
+03	O
+%	O
+,	O
+0	O
+.	O
+075	O
+%	O
+,	O
+0	O
+.	O
+15	O
+%	O
+,	O
+0	O
+.	O
+75	O
+%	O
+,	O
+1	O
+.	O
+5	O
+%	O
+,	O
+3	O
+%	O
+,	O
+and	O
+6	O
+%	O
+and	O
+1	O
+%	O
+,	O
+5	O
+%	O
+,	O
+and	O
+10	O
+%	O
+,	O
+respectively	O
+.	O
+
+Both	O
+compounds	O
+caused	O
+deformations	B-Disease
+and	O
+lethality	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+.	O
+
+All	O
+concentrations	O
+of	O
+nicotine	B-Chemical
+sulfate	O
+caused	O
+some	O
+lethality	O
+but	O
+a	O
+no	O
+effect	O
+level	O
+for	O
+coniine	B-Chemical
+lethality	O
+was	O
+0	O
+.	O
+75	O
+%	O
+.	O
+
+The	O
+deformations	B-Disease
+caused	O
+by	O
+both	O
+coniine	B-Chemical
+and	O
+nicotine	B-Chemical
+sulfate	O
+were	O
+excessive	B-Disease
+flexion	I-Disease
+or	I-Disease
+extension	I-Disease
+of	I-Disease
+one	I-Disease
+or	I-Disease
+more	I-Disease
+toes	I-Disease
+.	O
+
+No	O
+histopathological	O
+alterations	O
+or	O
+differences	O
+in	O
+bone	O
+formation	O
+were	O
+seen	O
+in	O
+the	O
+limbs	O
+or	O
+toes	O
+of	O
+any	O
+chicks	O
+from	O
+any	O
+group	O
+;	O
+however	O
+,	O
+extensive	O
+cranial	B-Disease
+hemorrhage	I-Disease
+occurred	O
+in	O
+all	O
+nicotine	B-Chemical
+sulfate	O
+-	O
+treated	O
+chicks	O
+.	O
+
+There	O
+was	O
+a	O
+statistically	O
+significant	O
+(	O
+P	O
+<	O
+or	O
+=	O
+0	O
+.	O
+01	O
+)	O
+decrease	O
+in	O
+movement	O
+in	O
+coniine	B-Chemical
+and	O
+nicotine	B-Chemical
+sulfate	O
+treated	O
+chicks	O
+as	O
+determined	O
+by	O
+ultrasound	O
+.	O
+
+Control	O
+chicks	O
+were	O
+in	O
+motion	O
+an	O
+average	O
+of	O
+33	O
+.	O
+67	O
+%	O
+of	O
+the	O
+time	O
+,	O
+while	O
+coniine	B-Chemical
+-	O
+treated	O
+chicks	O
+were	O
+only	O
+moving	O
+8	O
+.	O
+95	O
+%	O
+of	O
+a	O
+5	O
+-	O
+min	O
+interval	O
+,	O
+and	O
+no	O
+movement	O
+was	O
+observed	O
+for	O
+nicotine	B-Chemical
+sulfate	O
+treated	O
+chicks	O
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+chick	O
+embryo	O
+provides	O
+a	O
+reliable	O
+and	O
+simple	O
+experimental	O
+animal	O
+model	O
+of	O
+coniine	B-Chemical
+-	O
+induced	O
+arthrogryposis	B-Disease
+.	O
+
+Data	O
+from	O
+this	O
+model	O
+support	O
+a	O
+mechanism	O
+involving	O
+nicotinic	O
+receptor	O
+blockade	O
+with	O
+subsequent	O
+decreased	O
+fetal	O
+movement	O
+.	O
+
+Immediate	O
+allergic	B-Disease
+reactions	I-Disease
+to	O
+amoxicillin	B-Chemical
+.	O
+
+A	O
+large	O
+group	O
+of	O
+patients	O
+with	O
+suspected	O
+allergic	B-Disease
+reactions	I-Disease
+to	O
+beta	B-Chemical
+-	I-Chemical
+lactam	I-Chemical
+antibiotics	O
+was	O
+evaluated	O
+.	O
+
+A	O
+detailed	O
+clinical	O
+history	O
+,	O
+together	O
+with	O
+skin	O
+tests	O
+,	O
+RAST	O
+(	O
+radioallergosorbent	O
+test	O
+)	O
+,	O
+and	O
+controlled	O
+challenge	O
+tests	O
+,	O
+was	O
+used	O
+to	O
+establish	O
+whether	O
+patients	O
+allergic	B-Disease
+to	O
+beta	B-Chemical
+-	I-Chemical
+lactam	I-Chemical
+antibiotics	O
+had	O
+selective	O
+immediate	O
+allergic	B-Disease
+responses	O
+to	O
+amoxicillin	B-Chemical
+(	O
+AX	B-Chemical
+)	O
+or	O
+were	O
+cross	O
+-	O
+reacting	O
+with	O
+other	O
+penicillin	B-Chemical
+derivatives	O
+.	O
+
+Skin	O
+tests	O
+were	O
+performed	O
+with	O
+benzylpenicilloyl	B-Chemical
+-	I-Chemical
+poly	I-Chemical
+-	I-Chemical
+L	I-Chemical
+-	I-Chemical
+lysine	I-Chemical
+(	O
+BPO	B-Chemical
+-	I-Chemical
+PLL	I-Chemical
+)	O
+,	O
+benzylpenicilloate	B-Chemical
+,	O
+benzylpenicillin	B-Chemical
+(	O
+PG	B-Chemical
+)	O
+,	O
+ampicillin	B-Chemical
+(	O
+AMP	B-Chemical
+)	O
+,	O
+and	O
+AX	B-Chemical
+.	O
+
+RAST	O
+for	O
+BPO	B-Chemical
+-	I-Chemical
+PLL	I-Chemical
+and	O
+AX	B-Chemical
+-	O
+PLL	O
+was	O
+done	O
+.	O
+
+When	O
+both	O
+skin	O
+test	O
+and	O
+RAST	O
+for	O
+BPO	B-Chemical
+were	O
+negative	O
+,	O
+single	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+challenge	O
+tests	O
+were	O
+done	O
+to	O
+ensure	O
+tolerance	O
+of	O
+PG	B-Chemical
+or	O
+sensitivity	O
+to	O
+AX	B-Chemical
+.	O
+
+A	O
+total	O
+of	O
+177	O
+patients	O
+were	O
+diagnosed	O
+as	O
+allergic	B-Disease
+to	O
+beta	B-Chemical
+-	I-Chemical
+lactam	I-Chemical
+antibiotics	O
+.	O
+
+We	O
+selected	O
+the	O
+54	O
+(	O
+30	O
+.	O
+5	O
+%	O
+)	O
+cases	O
+of	O
+immediate	O
+AX	B-Chemical
+allergy	B-Disease
+with	O
+good	O
+tolerance	O
+of	O
+PG	B-Chemical
+.	O
+
+Anaphylaxis	B-Disease
+was	O
+seen	O
+in	O
+37	O
+patients	O
+(	O
+69	O
+%	O
+)	O
+,	O
+the	O
+other	O
+17	O
+(	O
+31	O
+%	O
+)	O
+having	O
+urticaria	B-Disease
+and	O
+/	O
+or	O
+angioedema	B-Disease
+.	O
+
+All	O
+the	O
+patients	O
+were	O
+skin	O
+test	O
+negative	O
+to	O
+BPO	B-Chemical
+;	O
+49	O
+of	O
+51	O
+(	O
+96	O
+%	O
+)	O
+were	O
+also	O
+negative	O
+to	O
+MDM	B-Disease
+,	O
+and	O
+44	O
+of	O
+46	O
+(	O
+96	O
+%	O
+)	O
+to	O
+PG	B-Chemical
+.	O
+
+Skin	O
+tests	O
+with	O
+AX	B-Chemical
+were	O
+positive	O
+in	O
+34	O
+(	O
+63	O
+%	O
+)	O
+patients	O
+.	O
+
+RAST	O
+was	O
+positive	O
+for	O
+AX	B-Chemical
+in	O
+22	O
+patients	O
+(	O
+41	O
+%	O
+)	O
+and	O
+to	O
+BPO	B-Chemical
+in	O
+just	O
+5	O
+(	O
+9	O
+%	O
+)	O
+.	O
+
+None	O
+of	O
+the	O
+sera	O
+with	O
+negative	O
+RAST	O
+for	O
+AX	B-Chemical
+were	O
+positive	O
+to	O
+BPO	B-Chemical
+.	O
+
+Challenge	O
+tests	O
+with	O
+AX	B-Chemical
+were	O
+performed	O
+in	O
+23	O
+subjects	O
+(	O
+43	O
+%	O
+)	O
+to	O
+establish	O
+the	O
+diagnosis	O
+of	O
+immediate	O
+allergic	B-Disease
+reaction	I-Disease
+to	O
+AX	B-Chemical
+,	O
+and	O
+in	O
+15	O
+cases	O
+(	O
+28	O
+%	O
+)	O
+both	O
+skin	O
+test	O
+and	O
+RAST	O
+for	O
+AX	B-Chemical
+were	O
+negative	O
+.	O
+
+PG	B-Chemical
+was	O
+well	O
+tolerated	O
+by	O
+all	O
+54	O
+patients	O
+.	O
+
+We	O
+describe	O
+the	O
+largest	O
+group	O
+of	O
+AX	B-Chemical
+-	O
+allergic	B-Disease
+patients	O
+who	O
+have	O
+tolerated	O
+PG	B-Chemical
+reported	O
+so	O
+far	O
+.	O
+
+Diagnosis	O
+of	O
+these	O
+patients	O
+can	O
+be	O
+achieved	O
+only	O
+if	O
+specific	O
+AX	B-Chemical
+-	O
+related	O
+reagents	O
+are	O
+employed	O
+.	O
+
+Further	O
+studies	O
+are	O
+necessary	O
+to	O
+determine	O
+the	O
+exact	O
+extent	O
+of	O
+this	O
+problem	O
+and	O
+to	O
+improve	O
+the	O
+efficacy	O
+of	O
+diagnostic	O
+methods	O
+.	O
+
+Reversal	O
+by	O
+phenylephrine	B-Chemical
+of	O
+the	O
+beneficial	O
+effects	O
+of	O
+intravenous	O
+nitroglycerin	B-Chemical
+in	O
+patients	O
+with	O
+acute	B-Disease
+myocardial	I-Disease
+infarction	I-Disease
+.	O
+
+Nitroglycerin	B-Chemical
+has	O
+been	O
+shown	O
+to	O
+reduce	O
+ST	O
+-	O
+segment	O
+elevation	O
+during	O
+acute	B-Disease
+myocardial	I-Disease
+infarction	I-Disease
+,	O
+an	O
+effect	O
+potentiated	O
+in	O
+the	O
+dog	O
+by	O
+agents	O
+that	O
+reverse	O
+nitroglycerin	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+Our	O
+study	O
+was	O
+designed	O
+to	O
+determine	O
+the	O
+effects	O
+of	O
+combined	O
+nitroglycerin	B-Chemical
+and	O
+phenylephrine	B-Chemical
+therapy	O
+.	O
+
+Ten	O
+patients	O
+with	O
+acute	O
+transmural	O
+myocardial	B-Disease
+infarctions	I-Disease
+received	O
+intravenous	O
+nitroglycerin	B-Chemical
+,	O
+sufficient	O
+to	O
+reduce	O
+mean	O
+arterial	O
+pressure	O
+from	O
+107	O
++	O
+/	O
+-	O
+6	O
+to	O
+85	O
++	O
+/	O
+-	O
+6	O
+mm	O
+Hg	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+,	O
+for	O
+60	O
+minutes	O
+.	O
+
+Left	O
+ventricular	O
+filling	O
+pressure	O
+decreased	O
+from	O
+19	O
++	O
+/	O
+-	O
+2	O
+to	O
+11	O
++	O
+/	O
+-	O
+2	O
+mm	O
+Hg	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+SigmaST	O
+,	O
+the	O
+sum	O
+of	O
+ST	O
+-	O
+segment	O
+elevations	O
+in	O
+16	O
+precordial	O
+leads	O
+,	O
+decreased	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+02	O
+)	O
+with	O
+intravenous	O
+nitroglycerin	B-Chemical
+.	O
+
+Subsequent	O
+addition	O
+of	O
+phenylephrine	B-Chemical
+infusion	O
+,	O
+sufficient	O
+to	O
+re	O
+-	O
+elevate	O
+mean	O
+arterial	O
+pressure	O
+to	O
+106	O
++	O
+/	O
+-	O
+4	O
+mm	O
+Hg	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+001	O
+)	O
+for	O
+30	O
+minutes	O
+,	O
+increased	O
+left	O
+ventricular	O
+filling	O
+pressure	O
+to	O
+17	O
++	O
+/	O
+-	O
+2	O
+mm	O
+Hg	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+and	O
+also	O
+significantly	O
+increased	O
+sigmaST	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+addition	O
+of	O
+phenylephrine	B-Chemical
+to	O
+nitroglycerin	B-Chemical
+is	O
+not	O
+beneficial	O
+in	O
+the	O
+treatment	O
+of	O
+patients	O
+with	O
+acute	B-Disease
+myocardial	I-Disease
+infarction	I-Disease
+.	O
+
+Acetazolamide	B-Chemical
+-	O
+induced	O
+nephrolithiasis	B-Disease
+:	O
+implications	O
+for	O
+treatment	O
+of	O
+neuromuscular	B-Disease
+disorders	I-Disease
+.	O
+
+Carbonic	O
+anhydrase	O
+inhibitors	O
+can	O
+cause	O
+nephrolithiasis	B-Disease
+.	O
+
+We	O
+studied	O
+20	O
+patients	O
+receiving	O
+long	O
+-	O
+term	O
+carbonic	O
+anhydrase	O
+inhibitor	O
+treatment	O
+for	O
+periodic	O
+paralysis	B-Disease
+and	O
+myotonia	B-Disease
+.	O
+
+Three	O
+patients	O
+on	O
+acetazolamide	B-Chemical
+(	O
+15	O
+%	O
+)	O
+developed	O
+renal	B-Disease
+calculi	I-Disease
+.	O
+
+Extracorporeal	O
+lithotripsy	O
+successfully	O
+removed	O
+a	O
+renal	B-Disease
+calculus	I-Disease
+in	O
+one	O
+patient	O
+and	O
+surgery	O
+removed	O
+a	O
+staghorn	O
+calculus	B-Disease
+in	O
+another	O
+,	O
+permitting	O
+continued	O
+treatment	O
+.	O
+
+Renal	O
+function	O
+remained	O
+normal	O
+in	O
+all	O
+patients	O
+.	O
+
+Nephrolithiasis	B-Disease
+is	O
+a	O
+complication	O
+of	O
+acetazolamide	B-Chemical
+but	O
+does	O
+not	O
+preclude	O
+its	O
+use	O
+.	O
+
+Effects	O
+of	O
+calcium	B-Chemical
+channel	O
+blockers	O
+on	O
+bupivacaine	B-Chemical
+-	O
+induced	O
+toxicity	B-Disease
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+investigate	O
+the	O
+influence	O
+of	O
+calcium	B-Chemical
+channel	O
+blockers	O
+on	O
+bupivacaine	B-Chemical
+-	O
+induced	O
+acute	O
+toxicity	B-Disease
+.	O
+
+For	O
+each	O
+of	O
+the	O
+three	O
+tested	O
+calcium	B-Chemical
+channel	O
+blockers	O
+(	O
+diltiazem	B-Chemical
+,	O
+verapamil	B-Chemical
+and	O
+bepridil	B-Chemical
+)	O
+6	O
+groups	O
+of	O
+mice	O
+were	O
+treated	O
+by	O
+two	O
+different	O
+doses	O
+,	O
+i	O
+.	O
+e	O
+.	O
+2	O
+and	O
+10	O
+mg	O
+/	O
+kg	O
+/	O
+i	O
+.	O
+p	O
+.	O
+,	O
+or	O
+an	O
+equal	O
+volume	O
+of	O
+saline	O
+for	O
+the	O
+control	O
+group	O
+(	O
+n	O
+=	O
+20	O
+)	O
+;	O
+15	O
+minutes	O
+later	O
+,	O
+all	O
+the	O
+animals	O
+were	O
+injected	O
+with	O
+a	O
+single	O
+50	O
+mg	O
+/	O
+kg	O
+/	O
+i	O
+.	O
+p	O
+.	O
+dose	O
+of	O
+bupivacaine	B-Chemical
+.	O
+
+The	O
+convulsant	O
+activity	O
+,	O
+the	O
+time	O
+of	O
+latency	O
+to	O
+convulse	O
+and	O
+the	O
+mortality	O
+rate	O
+were	O
+assessed	O
+in	O
+each	O
+group	O
+.	O
+
+The	O
+local	O
+anesthetic	O
+-	O
+induced	O
+mortality	O
+was	O
+significantly	O
+increased	O
+by	O
+the	O
+three	O
+different	O
+calcium	B-Chemical
+channel	O
+blockers	O
+.	O
+
+The	O
+convulsant	O
+activity	O
+of	O
+bupivacaine	B-Chemical
+was	O
+not	O
+significantly	O
+modified	O
+but	O
+calcium	B-Chemical
+channel	O
+blockers	O
+decreased	O
+the	O
+time	O
+of	O
+latency	O
+to	O
+obtain	O
+bupivacaine	B-Chemical
+-	O
+induced	O
+convulsions	B-Disease
+;	O
+this	O
+effect	O
+was	O
+less	O
+pronounced	O
+with	O
+bepridil	B-Chemical
+.	O
+
+Epidural	O
+blood	O
+flow	O
+during	O
+prostaglandin	B-Chemical
+E1	I-Chemical
+or	O
+trimethaphan	B-Chemical
+induced	O
+hypotension	B-Disease
+.	O
+
+To	O
+evaluate	O
+the	O
+effect	O
+of	O
+prostaglandin	B-Chemical
+E1	I-Chemical
+(	O
+PGE1	B-Chemical
+)	O
+or	O
+trimethaphan	B-Chemical
+(	O
+TMP	B-Chemical
+)	O
+induced	O
+hypotension	B-Disease
+on	O
+epidural	O
+blood	O
+flow	O
+(	O
+EBF	O
+)	O
+during	O
+spinal	O
+surgery	O
+,	O
+EBF	O
+was	O
+measured	O
+using	O
+the	O
+heat	O
+clearance	O
+method	O
+in	O
+30	O
+patients	O
+who	O
+underwent	O
+postero	O
+-	O
+lateral	O
+interbody	O
+fusion	O
+under	O
+isoflurane	B-Chemical
+anaesthesia	O
+.	O
+
+An	O
+initial	O
+dose	O
+of	O
+0	O
+.	O
+1	O
+microgram	O
+.	O
+kg	O
+-	O
+1	O
+.	O
+min	O
+-	O
+1	O
+of	O
+PGE1	B-Chemical
+(	O
+15	O
+patients	O
+)	O
+,	O
+or	O
+10	O
+micrograms	O
+.	O
+kg	O
+-	O
+1	O
+.	O
+min	O
+-	O
+1	O
+of	O
+TMP	B-Chemical
+(	O
+15	O
+patients	O
+)	O
+was	O
+administered	O
+intravenously	O
+after	O
+the	O
+dural	O
+opening	O
+and	O
+the	O
+dose	O
+was	O
+adjusted	O
+to	O
+maintain	O
+the	O
+mean	O
+arterial	O
+blood	O
+pressure	O
+(	O
+MAP	O
+)	O
+at	O
+about	O
+60	O
+mmHg	O
+.	O
+
+The	O
+hypotensive	B-Disease
+drug	O
+was	O
+discontinued	O
+at	O
+the	O
+completion	O
+of	O
+the	O
+operative	O
+procedure	O
+.	O
+
+After	O
+starting	O
+PGE1	B-Chemical
+or	O
+TMP	B-Chemical
+,	O
+MAP	O
+and	O
+rate	O
+pressure	O
+product	O
+(	O
+RPP	O
+)	O
+decreased	O
+significantly	O
+compared	O
+with	O
+preinfusion	O
+values	O
+(	O
+P	O
+<	O
+0	O
+.	O
+01	O
+)	O
+,	O
+and	O
+the	O
+degree	O
+of	O
+hypotension	B-Disease
+due	O
+to	O
+PGE1	B-Chemical
+remained	O
+constant	O
+until	O
+60	O
+min	O
+after	O
+its	O
+discontinuation	O
+.	O
+
+Heart	O
+rate	O
+(	O
+HR	O
+)	O
+did	O
+not	O
+change	O
+in	O
+either	O
+group	O
+.	O
+
+EBFF	O
+did	O
+not	O
+change	O
+during	O
+PGE1	B-Chemical
+infusion	O
+whereas	O
+in	O
+the	O
+TMP	B-Chemical
+group	O
+,	O
+EBF	O
+decreased	O
+significantly	O
+at	O
+30	O
+and	O
+60	O
+min	O
+after	O
+the	O
+start	O
+of	O
+TMP	B-Chemical
+(	O
+preinfusion	O
+:	O
+45	O
+.	O
+9	O
++	O
+/	O
+-	O
+13	O
+.	O
+9	O
+ml	O
+/	O
+100g	O
+/	O
+min	O
+.	O
+30	O
+min	O
+:	O
+32	O
+.	O
+3	O
++	O
+/	O
+-	O
+9	O
+.	O
+9	O
+ml	O
+/	O
+100	O
+g	O
+/	O
+min	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+60	O
+min	O
+:	O
+30	O
++	O
+/	O
+-	O
+7	O
+.	O
+5	O
+ml	O
+/	O
+100	O
+g	O
+/	O
+min	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+)	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+PGE1	B-Chemical
+may	O
+be	O
+preferable	O
+to	O
+TMP	B-Chemical
+for	O
+hypotensive	B-Disease
+anaesthesia	O
+in	O
+spinal	O
+surgery	O
+because	O
+TMP	B-Chemical
+decreased	O
+EBF	O
+.	O
+
+Dup	B-Chemical
+753	I-Chemical
+prevents	O
+the	O
+development	O
+of	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+-	O
+induced	O
+nephrosis	B-Disease
+.	O
+
+The	O
+appearance	O
+of	O
+nephrotic	B-Disease
+syndromes	I-Disease
+such	O
+as	O
+proteinuria	B-Disease
+,	O
+hypoalbuminemia	B-Disease
+,	O
+hypercholesterolemia	B-Disease
+and	O
+increase	O
+in	O
+blood	B-Chemical
+nitrogen	I-Chemical
+urea	I-Chemical
+,	O
+induced	O
+in	O
+rats	O
+by	O
+injection	O
+of	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+was	O
+markedly	O
+inhibited	O
+by	O
+oral	O
+administration	O
+of	O
+Dup	B-Chemical
+753	I-Chemical
+(	O
+losartan	B-Chemical
+)	O
+,	O
+a	O
+novel	O
+angiotensin	B-Chemical
+II	I-Chemical
+receptor	O
+antagonist	O
+,	O
+at	O
+a	O
+dose	O
+of	O
+1	O
+or	O
+2	O
+mg	O
+/	O
+kg	O
+per	O
+day	O
+.	O
+
+The	O
+results	O
+suggest	O
+a	O
+possible	O
+involvement	O
+of	O
+the	O
+renin	O
+-	O
+angiotensin	B-Chemical
+system	O
+in	O
+the	O
+development	O
+of	O
+puromycin	B-Chemical
+aminonucleoside	I-Chemical
+-	O
+induced	O
+nephrosis	B-Disease
+.	O
+
+Neuroplasticity	O
+of	O
+the	O
+adult	O
+primate	O
+auditory	O
+cortex	O
+following	O
+cochlear	O
+hearing	B-Disease
+loss	I-Disease
+.	O
+
+Tonotopic	O
+organization	O
+is	O
+an	O
+essential	O
+feature	O
+of	O
+the	O
+primary	O
+auditory	O
+area	O
+(	O
+A1	O
+)	O
+of	O
+primate	O
+cortex	O
+.	O
+
+In	O
+A1	O
+of	O
+macaque	O
+monkeys	O
+,	O
+low	O
+frequencies	O
+are	O
+represented	O
+rostrolaterally	O
+and	O
+high	O
+frequencies	O
+are	O
+represented	O
+caudomedially	O
+.	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+if	O
+changes	O
+occur	O
+in	O
+this	O
+tonotopic	O
+organization	O
+following	O
+cochlear	O
+hearing	B-Disease
+loss	I-Disease
+.	O
+
+Under	O
+anesthesia	O
+,	O
+the	O
+superior	O
+temporal	O
+gyrus	O
+of	O
+adult	O
+macaque	O
+monkeys	O
+was	O
+exposed	O
+,	O
+and	O
+the	O
+tonotopic	O
+organization	O
+of	O
+A1	O
+was	O
+mapped	O
+using	O
+conventional	O
+microelectrode	O
+recording	O
+techniques	O
+.	O
+
+Following	O
+recovery	O
+,	O
+the	O
+monkeys	O
+were	O
+selectively	O
+deafened	O
+for	O
+high	O
+frequencies	O
+using	O
+kanamycin	B-Chemical
+and	O
+furosemide	B-Chemical
+.	O
+
+The	O
+actual	O
+frequencies	O
+deafened	O
+were	O
+determined	O
+by	O
+the	O
+loss	O
+of	O
+tone	O
+-	O
+burst	O
+elicited	O
+auditory	O
+brainstem	O
+responses	O
+.	O
+
+Three	O
+months	O
+after	O
+deafening	O
+,	O
+A1	O
+was	O
+remapped	O
+.	O
+
+Postmortem	O
+cytoarchitectural	O
+features	O
+identifying	O
+A1	O
+were	O
+correlated	O
+with	O
+the	O
+electrophysiologic	O
+data	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+the	O
+deprived	O
+area	O
+of	O
+A1	O
+undergoes	O
+extensive	O
+reorganization	O
+and	O
+becomes	O
+responsive	O
+to	O
+intact	O
+cochlear	O
+frequencies	O
+.	O
+
+The	O
+region	O
+of	O
+cortex	O
+that	O
+represents	O
+the	O
+low	O
+frequencies	O
+was	O
+not	O
+obviously	O
+affected	O
+by	O
+the	O
+cochlear	O
+hearing	B-Disease
+loss	I-Disease
+.	O
+
+Sodium	B-Chemical
+bicarbonate	I-Chemical
+alleviates	O
+penile	B-Disease
+pain	I-Disease
+induced	O
+by	O
+intracavernous	O
+injections	O
+for	O
+erectile	B-Disease
+dysfunction	I-Disease
+.	O
+
+In	O
+an	O
+attempt	O
+to	O
+determine	O
+whether	O
+penile	B-Disease
+pain	I-Disease
+associated	O
+with	O
+intracorporeal	O
+injections	O
+could	O
+be	O
+due	O
+to	O
+the	O
+acidity	O
+of	O
+the	O
+medication	O
+,	O
+we	O
+performed	O
+a	O
+randomized	O
+study	O
+comparing	O
+the	O
+incidence	O
+of	O
+penile	B-Disease
+pain	I-Disease
+following	O
+intracorporeal	O
+injections	O
+with	O
+or	O
+without	O
+the	O
+addition	O
+of	O
+sodium	B-Chemical
+bicarbonate	I-Chemical
+to	O
+the	O
+intracorporeal	O
+medications	O
+.	O
+
+A	O
+total	O
+of	O
+38	O
+consecutive	O
+patients	O
+who	O
+presented	O
+to	O
+our	O
+clinic	O
+with	O
+impotence	B-Disease
+received	O
+0	O
+.	O
+2	O
+ml	O
+.	O
+of	O
+a	O
+combination	O
+of	O
+3	O
+drugs	O
+:	O
+6	O
+mg	O
+.	O
+papaverine	B-Chemical
+,	O
+100	O
+micrograms	O
+.	O
+phentolamine	B-Chemical
+and	O
+10	O
+micrograms	O
+.	O
+prostaglandin	B-Chemical
+E1	I-Chemical
+with	O
+(	O
+pH	O
+7	O
+.	O
+05	O
+)	O
+or	O
+without	O
+(	O
+pH	O
+4	O
+.	O
+17	O
+)	O
+the	O
+addition	O
+of	O
+sodium	B-Chemical
+bicarbonate	I-Chemical
+(	O
+0	O
+.	O
+03	O
+mEq	O
+.	O
+)	O
+.	O
+
+Of	O
+the	O
+19	O
+patients	O
+without	O
+sodium	B-Chemical
+bicarbonate	I-Chemical
+added	O
+to	O
+the	O
+medication	O
+11	O
+(	O
+58	O
+%	O
+)	O
+complained	O
+of	O
+penile	B-Disease
+pain	I-Disease
+due	O
+to	O
+the	O
+medication	O
+,	O
+while	O
+only	O
+1	O
+of	O
+the	O
+19	O
+men	O
+(	O
+5	O
+%	O
+)	O
+who	O
+received	O
+sodium	B-Chemical
+bicarbonate	I-Chemical
+complained	O
+of	O
+penile	B-Disease
+pain	I-Disease
+.	O
+
+From	O
+these	O
+data	O
+we	O
+conclude	O
+that	O
+the	O
+penile	B-Disease
+pain	I-Disease
+following	O
+intracorporeal	O
+injections	O
+is	O
+most	O
+likely	O
+due	O
+to	O
+the	O
+acidity	O
+of	O
+the	O
+medication	O
+,	O
+which	O
+can	O
+be	O
+overcome	O
+by	O
+elevating	O
+the	O
+pH	O
+to	O
+a	O
+neutral	O
+level	O
+.	O
+
+The	O
+use	O
+and	O
+toxicity	B-Disease
+of	O
+didanosine	B-Chemical
+(	O
+ddI	B-Chemical
+)	O
+in	O
+HIV	B-Disease
+antibody	I-Disease
+-	I-Disease
+positive	I-Disease
+individuals	O
+intolerant	O
+to	O
+zidovudine	B-Chemical
+(	O
+AZT	B-Chemical
+)	O
+
+One	O
+hundred	O
+and	O
+fifty	O
+-	O
+one	O
+patients	O
+intolerant	O
+to	O
+zidovudine	B-Chemical
+(	O
+AZT	B-Chemical
+)	O
+received	O
+didanosine	B-Chemical
+(	O
+ddI	B-Chemical
+)	O
+to	O
+a	O
+maximum	O
+dose	O
+of	O
+12	O
+.	O
+5	O
+mg	O
+/	O
+kg	O
+/	O
+day	O
+.	O
+
+Patient	O
+response	O
+was	O
+assessed	O
+using	O
+changes	O
+in	O
+CD4	O
++	O
+lymphocyte	O
+subset	O
+count	O
+,	O
+HIV	O
+p24	O
+antigen	O
+,	O
+weight	O
+,	O
+and	O
+quality	O
+of	O
+life	O
+.	O
+
+Seventy	O
+patients	O
+developed	O
+major	O
+opportunistic	B-Disease
+infections	I-Disease
+whilst	O
+on	O
+therapy	O
+;	O
+this	O
+was	O
+the	O
+first	O
+AIDS	B-Disease
+diagnosis	O
+in	O
+17	O
+.	O
+
+Only	O
+minor	O
+changes	O
+in	O
+CD4	O
++	O
+lymphocyte	O
+subset	O
+count	O
+were	O
+observed	O
+in	O
+AIDS	B-Disease
+patients	O
+,	O
+although	O
+a	O
+more	O
+significant	O
+rise	O
+occurred	O
+in	O
+those	O
+with	O
+earlier	O
+stages	O
+of	O
+disease	O
+.	O
+
+Of	O
+those	O
+positive	O
+for	O
+p24	O
+antigen	O
+at	O
+the	O
+commencement	O
+of	O
+the	O
+study	O
+67	O
+%	O
+showed	O
+a	O
+positive	O
+response	O
+,	O
+and	O
+this	O
+was	O
+most	O
+likely	O
+in	O
+those	O
+with	O
+CD4	O
++	O
+lymphocyte	O
+subset	O
+counts	O
+above	O
+100	O
+mm3	O
+.	O
+
+A	O
+positive	O
+weight	O
+response	O
+was	O
+seen	O
+in	O
+16	O
+%	O
+of	O
+patients	O
+.	O
+
+Most	O
+patients	O
+showed	O
+improvement	O
+in	O
+individual	O
+parameters	O
+and	O
+global	O
+score	O
+of	O
+quality	O
+of	O
+life	O
+.	O
+
+Adverse	O
+reactions	O
+possibly	O
+attributable	O
+to	O
+didanosine	B-Chemical
+were	O
+common	O
+.	O
+
+The	O
+most	O
+common	O
+side	O
+-	O
+effect	O
+was	O
+diarrhoea	B-Disease
+,	O
+which	O
+resulted	O
+in	O
+cessation	O
+of	O
+therapy	O
+in	O
+19	O
+individuals	O
+.	O
+
+Peripheral	B-Disease
+neuropathy	I-Disease
+occurred	O
+in	O
+12	O
+patients	O
+and	O
+pancreatitis	B-Disease
+in	O
+six	O
+.	O
+
+Thirteen	O
+patients	O
+developed	O
+a	O
+raised	O
+serum	O
+amylase	O
+without	O
+abdominal	B-Disease
+pain	I-Disease
+.	O
+
+Seven	O
+patients	O
+developed	O
+glucose	B-Disease
+tolerance	I-Disease
+curves	I-Disease
+characteristic	O
+of	O
+diabetes	B-Disease
+but	O
+these	O
+were	O
+mild	O
+,	O
+did	O
+not	O
+require	O
+treatment	O
+and	O
+returned	O
+to	O
+normal	O
+on	O
+ceasing	O
+didanosine	B-Chemical
+.	O
+
+Immunohistochemical	O
+studies	O
+with	O
+antibodies	O
+to	O
+neurofilament	O
+proteins	O
+on	O
+axonal	B-Disease
+damage	I-Disease
+in	O
+experimental	O
+focal	O
+lesions	O
+in	O
+rat	O
+.	O
+
+Immunohistochemistry	O
+with	O
+monoclonal	O
+antibodies	O
+against	O
+neurofilament	O
+(	O
+NF	O
+)	O
+proteins	O
+of	O
+middle	O
+and	O
+high	O
+molecular	O
+weight	O
+class	O
+,	O
+NF	O
+-	O
+M	O
+and	O
+NF	O
+-	O
+H	O
+,	O
+was	O
+used	O
+to	O
+study	O
+axonal	B-Disease
+injury	I-Disease
+in	O
+the	O
+borderzone	O
+of	O
+focal	O
+lesions	O
+in	O
+rats	O
+.	O
+
+Focal	O
+injury	B-Disease
+in	I-Disease
+the	I-Disease
+cortex	I-Disease
+was	O
+produced	O
+by	O
+infusion	O
+of	O
+lactate	B-Chemical
+at	O
+acid	O
+pH	O
+or	O
+by	O
+stab	O
+caused	O
+by	O
+needle	O
+insertion	O
+.	O
+
+Infarcts	B-Disease
+in	I-Disease
+substantia	I-Disease
+nigra	I-Disease
+pars	I-Disease
+reticulata	I-Disease
+were	O
+evoked	O
+by	O
+prolonged	O
+pilocarpine	B-Chemical
+-	O
+induced	O
+status	B-Disease
+epilepticus	I-Disease
+.	O
+
+Immunohistochemical	O
+staining	O
+for	O
+NFs	O
+showed	O
+characteristic	O
+terminal	O
+clubs	O
+of	O
+axons	O
+in	O
+the	O
+borderzone	O
+of	O
+lesions	O
+.	O
+
+Differences	O
+in	O
+the	O
+labelling	O
+pattern	O
+occurred	O
+with	O
+different	O
+antibodies	O
+which	O
+apparently	O
+depended	O
+on	O
+molecular	O
+weight	O
+class	O
+of	O
+NFs	O
+and	O
+phosphorylation	O
+state	O
+.	O
+
+These	O
+immunohistochemical	O
+changes	O
+of	O
+NFs	O
+can	O
+serve	O
+as	O
+a	O
+marker	O
+for	O
+axonal	B-Disease
+damage	I-Disease
+in	O
+various	O
+experimental	O
+traumatic	B-Disease
+or	O
+ischemic	O
+lesions	O
+.	O
+
+Pharmacokinetic	O
+and	O
+clinical	O
+studies	O
+in	O
+patients	O
+with	O
+cimetidine	B-Chemical
+-	O
+associated	O
+mental	O
+confusion	B-Disease
+.	O
+
+15	O
+cases	O
+of	O
+cimetidine	B-Chemical
+-	O
+associated	O
+mental	O
+confusion	B-Disease
+have	O
+been	O
+reported	O
+.	O
+
+In	O
+order	O
+that	O
+this	O
+syndrome	O
+might	O
+be	O
+investigated	O
+changes	O
+in	O
+mental	O
+status	O
+(	O
+M	O
+.	O
+S	O
+.	O
+)	O
+were	O
+correlated	O
+with	O
+serum	O
+concentrations	O
+and	O
+renal	O
+and	O
+hepatic	O
+function	O
+in	O
+36	O
+patients	O
+,	O
+30	O
+patients	O
+had	O
+no	O
+M	O
+.	O
+S	O
+.	O
+change	O
+on	O
+cimetidine	B-Chemical
+and	O
+6	O
+had	O
+moderate	O
+to	O
+severe	O
+changes	O
+.	O
+
+These	O
+6	O
+patients	O
+had	O
+both	O
+renal	B-Disease
+and	I-Disease
+liver	I-Disease
+dysfunction	I-Disease
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+,	O
+as	O
+well	O
+as	O
+cimetidine	B-Chemical
+trough	O
+-	O
+concentrations	O
+of	O
+more	O
+than	O
+1	O
+.	O
+25	O
+microgram	O
+/	O
+ml	O
+(	O
+P	O
+less	O
+than	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+severity	O
+of	O
+M	O
+.	O
+S	O
+.	O
+changes	O
+increased	O
+as	O
+trough	O
+-	O
+concentrations	O
+rose	O
+,	O
+5	O
+patients	O
+had	O
+lumbar	O
+puncture	O
+.	O
+
+The	O
+cerebrospinal	O
+fluid	O
+:	O
+serum	O
+ratio	O
+of	O
+cimetidine	B-Chemical
+concentrations	O
+was	O
+0	O
+.	O
+24	O
+:	O
+1	O
+and	O
+indicates	O
+that	O
+cimetidine	B-Chemical
+passes	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+;	O
+it	O
+also	O
+raises	O
+the	O
+possibility	O
+that	O
+M	O
+.	O
+S	O
+.	O
+changes	O
+are	O
+due	O
+to	O
+blockade	O
+of	O
+histamine	B-Chemical
+H2	O
+-	O
+receptors	O
+in	O
+the	O
+central	O
+nervous	O
+system	O
+.	O
+
+Patients	O
+likely	O
+to	O
+have	O
+both	O
+raised	O
+trough	O
+-	O
+concentrations	O
+and	O
+mental	O
+confusion	B-Disease
+are	O
+those	O
+with	O
+both	O
+severe	O
+renal	B-Disease
+and	I-Disease
+hepatic	I-Disease
+dysfunction	I-Disease
+.	O
+
+They	O
+should	O
+be	O
+closely	O
+observed	O
+and	O
+should	O
+be	O
+given	O
+reduced	O
+doses	O
+of	O
+cimetidine	B-Chemical
+.	O
+
+Prospective	O
+study	O
+of	O
+the	O
+long	O
+-	O
+term	O
+effects	O
+of	O
+somatostatin	O
+analog	O
+(	O
+octreotide	B-Chemical
+)	O
+on	O
+gallbladder	O
+function	O
+and	O
+gallstone	B-Disease
+formation	O
+in	O
+Chinese	O
+acromegalic	B-Disease
+patients	O
+.	O
+
+This	O
+article	O
+reports	O
+the	O
+changes	O
+in	O
+gallbladder	O
+function	O
+examined	O
+by	O
+ultrasonography	O
+in	O
+20	O
+Chinese	O
+patients	O
+with	O
+active	O
+acromegaly	B-Disease
+treated	O
+with	O
+sc	O
+injection	O
+of	O
+the	O
+somatostatin	O
+analog	O
+octreotide	B-Chemical
+in	O
+dosages	O
+of	O
+300	O
+-	O
+1500	O
+micrograms	O
+/	O
+day	O
+for	O
+a	O
+mean	O
+of	O
+24	O
+.	O
+2	O
++	O
+/	O
+-	O
+13	O
+.	O
+9	O
+months	O
+.	O
+
+During	O
+treatment	O
+with	O
+octreotide	B-Chemical
+,	O
+17	O
+patients	O
+developed	O
+sludge	O
+,	O
+10	O
+had	O
+gallstones	B-Disease
+,	O
+and	O
+1	O
+developed	O
+acute	B-Disease
+cholecystitis	I-Disease
+requiring	O
+surgery	O
+.	O
+
+In	O
+all	O
+of	O
+7	O
+patients	O
+examined	O
+acutely	O
+,	O
+gallbladder	O
+contractility	O
+was	O
+inhibited	O
+after	O
+a	O
+single	O
+100	O
+-	O
+micrograms	O
+injection	O
+.	O
+
+In	O
+8	O
+patients	O
+followed	O
+for	O
+24	O
+weeks	O
+,	O
+gallbladder	O
+contractility	O
+remained	O
+depressed	B-Disease
+throughout	O
+therapy	O
+.	O
+
+After	O
+withdrawal	O
+of	O
+octreotide	B-Chemical
+in	O
+10	O
+patients	O
+without	O
+gallstones	B-Disease
+,	O
+8	O
+patients	O
+assessed	O
+had	O
+return	O
+of	O
+normal	O
+gallbladder	O
+contractility	O
+within	O
+1	O
+month	O
+.	O
+
+In	O
+8	O
+of	O
+the	O
+remaining	O
+10	O
+patients	O
+who	O
+developed	O
+gallstones	B-Disease
+during	O
+treatment	O
+,	O
+gallbladder	O
+contractility	O
+normalized	O
+in	O
+5	O
+patients	O
+(	O
+3	O
+of	O
+whom	O
+has	O
+disappearance	O
+of	O
+their	O
+stones	O
+within	O
+3	O
+weeks	O
+)	O
+,	O
+and	O
+remained	O
+depressed	B-Disease
+in	O
+3	O
+(	O
+2	O
+of	O
+whom	O
+had	O
+stones	O
+present	O
+at	O
+6	O
+months	O
+)	O
+.	O
+
+Our	O
+results	O
+suggest	O
+that	O
+the	O
+suppression	O
+of	O
+gallbladder	O
+contractility	O
+is	O
+the	O
+cause	O
+of	O
+the	O
+successive	O
+formation	O
+of	O
+bile	O
+sludge	O
+,	O
+gallstones	B-Disease
+,	O
+and	O
+cholecystitis	B-Disease
+during	O
+octreotide	B-Chemical
+therapy	O
+in	O
+Chinese	O
+acromegalic	B-Disease
+patients	O
+.	O
+
+It	O
+is	O
+therefore	O
+very	O
+important	O
+to	O
+follow	O
+the	O
+changes	O
+of	O
+gallbladder	O
+function	O
+during	O
+long	O
+-	O
+term	O
+octreotide	B-Chemical
+therapy	O
+of	O
+acromegalic	B-Disease
+patients	O
+.	O
+
+Increase	O
+of	O
+Parkinson	B-Disease
+disability	I-Disease
+after	O
+fluoxetine	B-Chemical
+medication	O
+.	O
+
+Depression	B-Disease
+is	O
+a	O
+major	O
+clinical	O
+feature	O
+of	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+We	O
+report	O
+the	O
+increased	O
+amount	O
+of	O
+motor	B-Disease
+disability	I-Disease
+in	O
+four	O
+patients	O
+with	O
+idiopathic	B-Disease
+Parkinson	I-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+after	O
+exposure	O
+to	O
+the	O
+antidepressant	B-Chemical
+fluoxetine	B-Chemical
+.	O
+
+The	O
+possibility	O
+of	O
+a	O
+clinically	O
+relevant	O
+dopamine	B-Chemical
+-	O
+antagonistic	O
+capacity	O
+of	O
+fluoxetine	B-Chemical
+in	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+patients	O
+must	O
+be	O
+considered	O
+.	O
+
+Sinus	B-Disease
+arrest	I-Disease
+associated	O
+with	O
+continuous	O
+-	O
+infusion	O
+cimetidine	B-Chemical
+.	O
+
+The	O
+administration	O
+of	O
+intermittent	O
+intravenous	O
+infusions	O
+of	O
+cimetidine	B-Chemical
+is	O
+infrequently	O
+associated	O
+with	O
+the	O
+development	O
+of	O
+bradyarrhythmias	B-Disease
+.	O
+
+A	O
+40	O
+-	O
+year	O
+-	O
+old	O
+man	O
+with	O
+leukemia	B-Disease
+and	O
+no	O
+history	O
+of	O
+cardiac	B-Disease
+disease	I-Disease
+developed	O
+recurrent	O
+,	O
+brief	O
+episodes	O
+of	O
+apparent	O
+sinus	B-Disease
+arrest	I-Disease
+while	O
+receiving	O
+continuous	O
+-	O
+infusion	O
+cimetidine	B-Chemical
+50	O
+mg	O
+/	O
+hour	O
+.	O
+
+The	O
+arrhythmias	B-Disease
+were	O
+temporally	O
+related	O
+to	O
+cimetidine	B-Chemical
+administration	O
+,	O
+disappeared	O
+after	O
+dechallenge	O
+,	O
+and	O
+did	O
+not	O
+recur	O
+during	O
+ranitidine	B-Chemical
+treatment	O
+.	O
+
+This	O
+is	O
+the	O
+first	O
+reported	O
+case	O
+of	O
+sinus	B-Disease
+arrest	I-Disease
+associated	O
+with	O
+continuous	O
+-	O
+infusion	O
+cimetidine	B-Chemical
+.	O
+
+Phase	O
+II	O
+trial	O
+of	O
+vinorelbine	B-Chemical
+in	O
+metastatic	O
+squamous	B-Disease
+cell	I-Disease
+esophageal	I-Disease
+carcinoma	I-Disease
+.	O
+
+European	O
+Organization	O
+for	O
+Research	O
+and	O
+Treatment	O
+of	O
+Cancer	B-Disease
+Gastrointestinal	O
+Treat	O
+Cancer	B-Disease
+Cooperative	O
+Group	O
+.	O
+
+PURPOSE	O
+:	O
+To	O
+evaluate	O
+the	O
+response	O
+rate	O
+and	O
+toxic	O
+effects	O
+of	O
+vinorelbine	B-Chemical
+(	O
+VNB	B-Chemical
+)	O
+administered	O
+as	O
+a	O
+single	O
+agent	O
+in	O
+metastatic	O
+squamous	B-Disease
+cell	I-Disease
+esophageal	I-Disease
+carcinoma	I-Disease
+.	O
+
+PATIENTS	O
+AND	O
+METHODS	O
+:	O
+Forty	O
+-	O
+six	O
+eligible	O
+patients	O
+with	O
+measurable	O
+lesions	O
+were	O
+included	O
+and	O
+were	O
+stratified	O
+according	O
+to	O
+previous	O
+chemotherapy	O
+.	O
+
+Thirty	O
+patients	O
+without	O
+prior	O
+chemotherapy	O
+and	O
+16	O
+pretreated	O
+with	O
+cisplatin	B-Chemical
+-	O
+based	O
+chemotherapy	O
+were	O
+assessable	O
+for	O
+toxicity	B-Disease
+and	O
+response	O
+.	O
+
+VNB	B-Chemical
+was	O
+administered	O
+weekly	O
+as	O
+a	O
+25	O
+-	O
+mg	O
+/	O
+m2	O
+short	O
+intravenous	O
+(	O
+i	O
+.	O
+v	O
+.	O
+)	O
+infusion	O
+.	O
+
+RESULTS	O
+:	O
+Six	O
+of	O
+30	O
+patients	O
+(	O
+20	O
+%	O
+)	O
+without	O
+prior	O
+chemotherapy	O
+achieved	O
+a	O
+partial	O
+response	O
+(	O
+PR	O
+)	O
+(	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+,	O
+8	O
+%	O
+to	O
+39	O
+%	O
+)	O
+.	O
+
+The	O
+median	O
+duration	O
+of	O
+response	O
+was	O
+21	O
+weeks	O
+(	O
+range	O
+,	O
+17	O
+to	O
+28	O
+)	O
+.	O
+
+One	O
+of	O
+16	O
+patients	O
+(	O
+6	O
+%	O
+)	O
+with	O
+prior	O
+chemotherapy	O
+had	O
+a	O
+complete	O
+response	O
+(	O
+CR	O
+)	O
+of	O
+31	O
+weeks	O
+'	O
+duration	O
+(	O
+95	O
+%	O
+CI	O
+,	O
+0	O
+%	O
+to	O
+30	O
+%	O
+)	O
+.	O
+
+The	O
+overall	O
+response	O
+rate	O
+(	O
+World	O
+Health	O
+Organization	O
+[	O
+WHO	O
+]	O
+criteria	O
+)	O
+was	O
+15	O
+%	O
+(	O
+CR	O
+,	O
+2	O
+%	O
+;	O
+PR	O
+13	O
+%	O
+;	O
+95	O
+%	O
+CI	O
+,	O
+6	O
+%	O
+to	O
+29	O
+%	O
+)	O
+.	O
+
+The	O
+median	O
+dose	O
+-	O
+intensity	O
+(	O
+DI	O
+)	O
+was	O
+20	O
+mg	O
+/	O
+m2	O
+/	O
+wk	O
+.	O
+
+VNB	B-Chemical
+was	O
+well	O
+tolerated	O
+and	O
+zero	O
+instances	O
+of	O
+WHO	O
+grade	O
+4	O
+nonhematologic	O
+toxicity	B-Disease
+occurred	O
+.	O
+
+At	O
+least	O
+one	O
+episode	O
+of	O
+grade	O
+3	O
+or	O
+4	O
+granulocytopenia	B-Disease
+was	O
+seen	O
+in	O
+59	O
+%	O
+of	O
+patients	O
+.	O
+
+A	O
+grade	O
+2	O
+or	O
+3	O
+infection	B-Disease
+occurred	O
+in	O
+16	O
+%	O
+of	O
+patients	O
+,	O
+but	O
+no	O
+toxic	O
+deaths	B-Disease
+occurred	O
+.	O
+
+Other	O
+side	O
+effects	O
+were	O
+rare	O
+,	O
+and	O
+peripheral	B-Disease
+neurotoxicity	I-Disease
+has	O
+been	O
+minor	O
+(	O
+26	O
+%	O
+grade	O
+1	O
+)	O
+.	O
+
+CONCLUSION	O
+:	O
+These	O
+data	O
+indicate	O
+that	O
+VNB	B-Chemical
+is	O
+an	O
+active	O
+agent	O
+in	O
+metastatic	O
+esophageal	B-Disease
+squamous	I-Disease
+cell	I-Disease
+carcinoma	I-Disease
+.	O
+
+Given	O
+its	O
+excellent	O
+tolerance	O
+profile	O
+and	O
+low	O
+toxicity	B-Disease
+,	O
+further	O
+evaluation	O
+of	O
+VNB	B-Chemical
+in	O
+combination	O
+therapy	O
+is	O
+warranted	O
+.	O
+
+Evaluation	O
+of	O
+adverse	O
+reactions	O
+of	O
+aponidine	B-Chemical
+hydrochloride	I-Chemical
+ophthalmic	O
+solution	O
+.	O
+
+We	O
+prospectively	O
+evaluated	O
+the	O
+adverse	O
+reactions	O
+of	O
+apraclonidine	B-Chemical
+in	O
+20	O
+normal	O
+volunteers	O
+by	O
+instilling	O
+a	O
+single	O
+drop	O
+of	O
+1	O
+%	O
+apraclonidine	B-Chemical
+in	O
+their	O
+right	O
+eyes	O
+.	O
+
+Examinations	O
+,	O
+including	O
+blood	O
+pressure	O
+,	O
+pulse	O
+rate	O
+,	O
+conjunctiva	O
+and	O
+cornea	O
+,	O
+intraocular	O
+pressure	O
+(	O
+IOP	O
+)	O
+,	O
+pupil	O
+diameter	O
+,	O
+basal	O
+tear	O
+secretion	O
+and	O
+margin	O
+reflex	O
+distance	O
+of	O
+both	O
+upper	O
+and	O
+lower	O
+eyelids	O
+,	O
+were	O
+performed	O
+prior	O
+to	O
+entry	O
+and	O
+at	O
+1	O
+,	O
+3	O
+,	O
+5	O
+and	O
+7	O
+hours	O
+after	O
+instillation	O
+.	O
+
+The	O
+ocular	B-Disease
+hypotensive	I-Disease
+effects	O
+were	O
+statistically	O
+significant	O
+for	O
+apraclonidine	B-Chemical
+-	O
+treated	O
+eyes	O
+throughout	O
+the	O
+study	O
+and	O
+also	O
+statistically	O
+significant	O
+for	O
+contralateral	O
+eyes	O
+from	O
+three	O
+hours	O
+after	O
+topical	O
+administration	O
+of	O
+1	O
+%	O
+apraclonidine	B-Chemical
+.	O
+
+Decreases	B-Disease
+in	I-Disease
+systolic	I-Disease
+blood	I-Disease
+pressure	I-Disease
+were	O
+statistically	O
+,	O
+but	O
+not	O
+clinically	O
+,	O
+significant	O
+.	O
+
+No	O
+significant	O
+changes	O
+in	O
+diastolic	O
+blood	O
+pressure	O
+,	O
+pulse	O
+rate	O
+and	O
+basal	O
+tear	O
+secretion	O
+were	O
+noted	O
+.	O
+
+Conjunctival	B-Disease
+blanching	I-Disease
+and	O
+mydriasis	B-Disease
+were	O
+commonly	O
+found	O
+.	O
+
+Upper	O
+lid	O
+retraction	O
+was	O
+frequently	O
+noted	O
+.	O
+
+While	O
+the	O
+elevations	O
+of	O
+the	O
+upper	O
+lid	O
+margin	O
+in	O
+most	O
+subjects	O
+were	O
+not	O
+more	O
+than	O
+2	O
+mm	O
+and	O
+did	O
+not	O
+cause	O
+noticeable	O
+change	O
+in	O
+appearance	O
+,	O
+one	O
+subject	O
+suffered	O
+from	O
+mechanical	O
+entropion	B-Disease
+and	O
+marked	O
+corneal	B-Disease
+abrasion	I-Disease
+3	O
+hours	O
+after	O
+instillation	O
+of	O
+the	O
+medication	O
+.	O
+
+This	O
+may	O
+well	O
+be	O
+a	O
+particularly	O
+notable	O
+finding	O
+in	O
+Asian	O
+people	O
+.	O
+
+Thiopentone	B-Chemical
+pretreatment	O
+for	O
+propofol	B-Chemical
+injection	O
+pain	B-Disease
+in	O
+ambulatory	O
+patients	O
+.	O
+
+This	O
+study	O
+investigated	O
+propofol	B-Chemical
+injection	O
+pain	B-Disease
+in	O
+patients	O
+undergoing	O
+ambulatory	O
+anaesthesia	O
+.	O
+
+In	O
+a	O
+randomized	O
+,	O
+double	O
+-	O
+blind	O
+trial	O
+,	O
+90	O
+women	O
+were	O
+allocated	O
+to	O
+receive	O
+one	O
+of	O
+three	O
+treatments	O
+prior	O
+to	O
+induction	O
+of	O
+anaesthesia	O
+with	O
+propofol	B-Chemical
+.	O
+
+Patients	O
+in	O
+Group	O
+C	O
+received	O
+2	O
+ml	O
+normal	O
+saline	O
+,	O
+Group	O
+L	O
+,	O
+2	O
+ml	O
+,	O
+lidocaine	B-Chemical
+2	O
+%	O
+(	O
+40	O
+mg	O
+)	O
+and	O
+Group	O
+T	O
+,	O
+2	O
+ml	O
+thiopentone	B-Chemical
+2	O
+.	O
+5	O
+%	O
+(	O
+50	O
+mg	O
+)	O
+.	O
+
+Venous	O
+discomfort	O
+was	O
+assessed	O
+with	O
+a	O
+visual	O
+analogue	O
+scale	O
+(	O
+VAS	O
+)	O
+5	O
+-	O
+15	O
+sec	O
+after	O
+commencing	O
+propofol	B-Chemical
+administration	O
+using	O
+an	O
+infusion	O
+pump	O
+(	O
+rate	O
+1000	O
+micrograms	O
+.	O
+kg	O
+-	O
+1	O
+.	O
+min	O
+-	O
+1	O
+)	O
+.	O
+
+Loss	B-Disease
+of	I-Disease
+consciousness	I-Disease
+occurred	O
+in	O
+60	O
+-	O
+90	O
+sec	O
+.	O
+
+Visual	O
+analogue	O
+scores	O
+(	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+)	O
+during	O
+induction	O
+were	O
+lower	O
+in	O
+Groups	O
+L	O
+(	O
+3	O
+.	O
+3	O
++	O
+/	O
+-	O
+2	O
+.	O
+5	O
+)	O
+and	O
+T	O
+(	O
+4	O
+.	O
+1	O
++	O
+/	O
+-	O
+2	O
+.	O
+7	O
+)	O
+than	O
+in	O
+Group	O
+C	O
+(	O
+5	O
+.	O
+6	O
++	O
+/	O
+-	O
+2	O
+.	O
+3	O
+)	O
+;	O
+P	O
+=	O
+0	O
+.	O
+0031	O
+.	O
+
+The	O
+incidence	O
+of	O
+venous	O
+discomfort	O
+was	O
+lower	O
+in	O
+Group	O
+L	O
+(	O
+76	O
+.	O
+6	O
+%	O
+;	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+than	O
+in	O
+Group	O
+C	O
+(	O
+100	O
+%	O
+)	O
+but	O
+not	O
+different	O
+from	O
+Group	O
+T	O
+(	O
+90	O
+%	O
+)	O
+.	O
+
+The	O
+VAS	O
+scores	O
+for	O
+recall	O
+of	O
+pain	B-Disease
+in	O
+the	O
+recovery	O
+room	O
+were	O
+correlated	O
+with	O
+the	O
+VAS	O
+scores	O
+during	O
+induction	O
+(	O
+r	O
+=	O
+0	O
+.	O
+7045	O
+;	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+Recovery	O
+room	O
+discharge	O
+times	O
+were	O
+similar	O
+:	O
+C	O
+(	O
+75	O
+.	O
+9	O
++	O
+/	O
+-	O
+19	O
+.	O
+4	O
+min	O
+)	O
+;	O
+L	O
+73	O
+.	O
+6	O
++	O
+/	O
+-	O
+21	O
+.	O
+6	O
+min	O
+)	O
+;	O
+T	O
+(	O
+77	O
+.	O
+1	O
++	O
+/	O
+-	O
+18	O
+.	O
+9	O
+min	O
+)	O
+.	O
+
+Assessing	O
+their	O
+overall	O
+satisfaction	O
+,	O
+89	O
+.	O
+7	O
+%	O
+would	O
+choose	O
+propofol	B-Chemical
+anaesthesia	O
+again	O
+.	O
+
+We	O
+conclude	O
+that	O
+lidocaine	B-Chemical
+reduces	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+propofol	B-Chemical
+injection	O
+pain	B-Disease
+in	O
+ambulatory	O
+patients	O
+whereas	O
+thiopentone	B-Chemical
+only	O
+reduces	O
+its	O
+severity	O
+.	O
+
+Persistent	O
+paralysis	B-Disease
+after	O
+prolonged	O
+use	O
+of	O
+atracurium	B-Chemical
+in	O
+the	O
+absence	O
+of	O
+corticosteroids	O
+.	O
+
+Neuromuscular	O
+blocking	O
+agents	O
+(	O
+NMBAs	O
+)	O
+are	O
+often	O
+used	O
+for	O
+patients	O
+requiring	O
+prolonged	O
+mechanical	O
+ventilation	O
+.	O
+
+Reports	O
+of	O
+persistent	O
+paralysis	B-Disease
+after	O
+the	O
+discontinuance	O
+of	O
+these	O
+drugs	O
+have	O
+most	O
+often	O
+involved	O
+aminosteroid	O
+-	O
+based	O
+NMBAs	O
+such	O
+as	O
+vecuronium	B-Chemical
+bromide	I-Chemical
+,	O
+especially	O
+when	O
+used	O
+in	O
+conjunction	O
+with	O
+corticosteroids	O
+.	O
+
+Atracurium	B-Chemical
+besylate	I-Chemical
+,	O
+a	O
+short	O
+-	O
+acting	O
+benzylisoquinolinium	B-Chemical
+NMBA	O
+that	O
+is	O
+eliminated	O
+independently	O
+of	O
+renal	O
+or	O
+hepatic	O
+function	O
+,	O
+has	O
+also	O
+been	O
+associated	O
+with	O
+persistent	O
+paralysis	B-Disease
+,	O
+but	O
+only	O
+when	O
+used	O
+with	O
+corticosteroids	O
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+atracurium	B-Chemical
+-	O
+related	O
+paralysis	B-Disease
+persisting	O
+for	O
+approximately	O
+50	O
+hours	O
+in	O
+a	O
+patient	O
+who	O
+was	O
+not	O
+treated	O
+with	O
+corticosteroids	O
+.	O
+
+A	O
+phase	O
+I	O
+/	O
+II	O
+study	O
+of	O
+paclitaxel	B-Chemical
+plus	O
+cisplatin	B-Chemical
+as	O
+first	O
+-	O
+line	O
+therapy	O
+for	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+cancers	I-Disease
+:	O
+preliminary	O
+results	O
+.	O
+
+Improved	O
+outcomes	O
+among	O
+patients	O
+with	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+carcinomas	I-Disease
+require	O
+investigations	O
+of	O
+new	O
+drugs	O
+for	O
+induction	O
+therapy	O
+.	O
+
+Preliminary	O
+results	O
+of	O
+an	O
+Eastern	O
+Cooperative	O
+Oncology	O
+Group	O
+study	O
+of	O
+single	O
+-	O
+agent	O
+paclitaxel	B-Chemical
+(	O
+Taxol	B-Chemical
+;	O
+Bristol	O
+-	O
+Myers	O
+Squibb	O
+Company	O
+,	O
+Princeton	O
+,	O
+NJ	O
+)	O
+reported	O
+a	O
+37	O
+%	O
+response	O
+rate	O
+in	O
+patients	O
+with	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+cancer	I-Disease
+,	O
+and	O
+the	O
+paclitaxel	B-Chemical
+/	O
+cisplatin	B-Chemical
+combination	O
+has	O
+been	O
+used	O
+successfully	O
+and	O
+has	O
+significantly	O
+improved	O
+median	O
+response	O
+duration	O
+in	O
+ovarian	B-Disease
+cancer	I-Disease
+patients	O
+.	O
+
+We	O
+initiated	O
+a	O
+phase	O
+I	O
+/	O
+II	O
+trial	O
+to	O
+determine	O
+the	O
+response	O
+and	O
+toxicity	B-Disease
+of	O
+escalating	O
+paclitaxel	B-Chemical
+doses	O
+combined	O
+with	O
+fixed	O
+-	O
+dose	O
+cisplatin	B-Chemical
+with	O
+granulocyte	O
+colony	O
+-	O
+stimulating	O
+factor	O
+support	O
+in	O
+patients	O
+with	O
+untreated	O
+locally	O
+advanced	O
+inoperable	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+carcinoma	I-Disease
+.	O
+
+To	O
+date	O
+,	O
+23	O
+men	O
+with	O
+a	O
+median	O
+age	O
+of	O
+50	O
+years	O
+and	O
+good	O
+performance	O
+status	O
+have	O
+entered	O
+the	O
+trial	O
+.	O
+
+Primary	O
+tumor	B-Disease
+sites	O
+were	O
+oropharynx	O
+,	O
+10	O
+patients	O
+;	O
+hypopharynx	O
+,	O
+four	O
+;	O
+larynx	O
+,	O
+two	O
+;	O
+oral	O
+cavity	O
+,	O
+three	O
+;	O
+unknown	O
+primary	O
+,	O
+two	O
+;	O
+and	O
+nasal	O
+cavity	O
+and	O
+parotid	O
+gland	O
+,	O
+one	O
+each	O
+.	O
+
+Of	O
+20	O
+patients	O
+evaluable	O
+for	O
+toxicity	B-Disease
+,	O
+four	O
+had	O
+stage	O
+III	O
+and	O
+16	O
+had	O
+stage	O
+IV	O
+disease	O
+.	O
+
+Treatment	O
+,	O
+given	O
+every	O
+21	O
+days	O
+for	O
+a	O
+maximum	O
+of	O
+three	O
+cycles	O
+,	O
+consisted	O
+of	O
+paclitaxel	B-Chemical
+by	O
+3	O
+-	O
+hour	O
+infusion	O
+followed	O
+the	O
+next	O
+day	O
+by	O
+a	O
+fixed	O
+dose	O
+of	O
+cisplatin	B-Chemical
+(	O
+75	O
+mg	O
+/	O
+m2	O
+)	O
+.	O
+
+The	O
+dose	O
+levels	O
+incorporate	O
+escalating	O
+paclitaxel	B-Chemical
+doses	O
+,	O
+and	O
+intrapatient	O
+escalations	O
+within	O
+a	O
+given	O
+dose	O
+level	O
+are	O
+permitted	O
+if	O
+toxicity	B-Disease
+permits	O
+.	O
+
+At	O
+the	O
+time	O
+of	O
+this	O
+writing	O
+,	O
+dose	O
+level	O
+4	O
+(	O
+260	O
+,	O
+270	O
+,	O
+and	O
+280	O
+mg	O
+/	O
+m2	O
+)	O
+is	O
+being	O
+evaluated	O
+;	O
+three	O
+patients	O
+from	O
+this	O
+level	O
+are	O
+evaluable	O
+.	O
+
+With	O
+paclitaxel	B-Chemical
+doses	O
+of	O
+200	O
+mg	O
+/	O
+m2	O
+and	O
+higher	O
+,	O
+granulocyte	O
+colony	O
+-	O
+stimulating	O
+factor	O
+5	O
+micrograms	O
+/	O
+kg	O
+/	O
+d	O
+is	O
+given	O
+(	O
+days	O
+4	O
+through	O
+12	O
+)	O
+.	O
+
+Of	O
+18	O
+patients	O
+evaluable	O
+for	O
+response	O
+,	O
+seven	O
+(	O
+39	O
+%	O
+)	O
+achieved	O
+a	O
+complete	O
+response	O
+and	O
+six	O
+(	O
+33	O
+%	O
+)	O
+achieved	O
+a	O
+partial	O
+response	O
+.	O
+
+Three	O
+patients	O
+had	O
+no	O
+change	O
+and	O
+disease	O
+progressed	O
+in	O
+two	O
+.	O
+
+The	O
+overall	O
+response	O
+rate	O
+is	O
+72	O
+%	O
+.	O
+
+Eleven	O
+responding	O
+patients	O
+had	O
+subsequent	O
+surgery	O
+/	O
+radiotherapy	O
+or	O
+radical	O
+radiotherapy	O
+.	O
+
+Two	O
+pathologic	O
+complete	O
+responses	O
+were	O
+observed	O
+in	O
+patients	O
+who	O
+had	O
+achieved	O
+clinical	O
+complete	O
+responses	O
+.	O
+
+Alopecia	B-Disease
+,	O
+paresthesias	B-Disease
+,	O
+and	O
+arthralgias	B-Disease
+/	O
+myalgias	B-Disease
+have	O
+occurred	O
+frequently	O
+,	O
+but	O
+with	O
+one	O
+exception	O
+(	O
+a	O
+grade	O
+3	O
+myalgia	B-Disease
+)	O
+they	O
+have	O
+been	O
+grade	O
+1	O
+or	O
+2	O
+.	O
+
+No	O
+dose	O
+-	O
+limiting	O
+hematologic	O
+toxicity	B-Disease
+has	O
+been	O
+seen	O
+.	O
+
+Paclitaxel	B-Chemical
+/	O
+cisplatin	B-Chemical
+is	O
+an	O
+effective	O
+first	O
+-	O
+line	O
+regimen	O
+for	O
+locoregionally	O
+advanced	O
+head	B-Disease
+and	I-Disease
+neck	I-Disease
+cancer	I-Disease
+and	O
+continued	O
+study	O
+is	O
+warranted	O
+.	O
+
+Results	O
+thus	O
+far	O
+suggest	O
+no	O
+dose	O
+-	O
+response	O
+effect	O
+for	O
+paclitaxel	B-Chemical
+doses	O
+above	O
+200	O
+mg	O
+/	O
+m2	O
+.	O
+
+Improvement	O
+of	O
+levodopa	B-Chemical
+-	O
+induced	O
+dyskinesia	B-Disease
+by	O
+propranolol	B-Chemical
+in	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+Seven	O
+patients	O
+suffering	O
+from	O
+Parkinson	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+(	O
+PD	B-Disease
+)	O
+with	O
+severely	O
+disabling	O
+dyskinesia	B-Disease
+received	O
+low	O
+-	O
+dose	O
+propranolol	B-Chemical
+as	O
+an	O
+adjunct	O
+to	O
+the	O
+currently	O
+used	O
+medical	O
+treatment	O
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+40	O
+%	O
+improvement	O
+in	O
+the	O
+dyskinesia	B-Disease
+score	O
+without	O
+increase	O
+of	O
+parkinsonian	B-Disease
+motor	B-Disease
+disability	I-Disease
+.	O
+
+Ballistic	O
+and	O
+choreic	O
+dyskinesia	B-Disease
+were	O
+markedly	O
+ameliorated	O
+,	O
+whereas	O
+dystonia	B-Disease
+was	O
+not	O
+.	O
+
+This	O
+study	O
+suggests	O
+that	O
+administration	O
+of	O
+low	O
+doses	O
+of	O
+beta	O
+-	O
+blockers	O
+may	O
+improve	O
+levodopa	B-Chemical
+-	O
+induced	O
+ballistic	O
+and	O
+choreic	O
+dyskinesia	B-Disease
+in	O
+PD	B-Disease
+.	O
+
+Habitual	O
+use	O
+of	O
+acetaminophen	B-Chemical
+as	O
+a	O
+risk	O
+factor	O
+for	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+:	O
+a	O
+comparison	O
+with	O
+phenacetin	B-Chemical
+.	O
+
+Six	O
+epidemiologic	O
+studies	O
+in	O
+the	O
+United	O
+States	O
+and	O
+Europe	O
+indicate	O
+that	O
+habitual	O
+use	O
+of	O
+phenacetin	B-Chemical
+is	O
+associated	O
+with	O
+the	O
+development	O
+of	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+and	O
+end	B-Disease
+-	I-Disease
+stage	I-Disease
+renal	I-Disease
+disease	I-Disease
+(	O
+ESRD	B-Disease
+)	O
+,	O
+with	O
+a	O
+relative	O
+risk	O
+in	O
+the	O
+range	O
+of	O
+4	O
+to	O
+19	O
+.	O
+
+As	O
+a	O
+result	O
+of	O
+these	O
+and	O
+other	O
+studies	O
+,	O
+phenacetin	B-Chemical
+has	O
+now	O
+been	O
+withdrawn	O
+from	O
+the	O
+market	O
+in	O
+most	O
+countries	O
+.	O
+
+However	O
+,	O
+three	O
+case	O
+control	O
+studies	O
+,	O
+one	O
+each	O
+in	O
+North	O
+Carolina	O
+,	O
+northern	O
+Maryland	O
+,	O
+and	O
+West	O
+Berlin	O
+,	O
+Germany	O
+,	O
+showed	O
+that	O
+habitual	O
+use	O
+of	O
+acetaminophen	B-Chemical
+is	O
+also	O
+associated	O
+with	O
+chronic	B-Disease
+renal	I-Disease
+failure	I-Disease
+and	O
+ESRD	B-Disease
+,	O
+with	O
+a	O
+relative	O
+risk	O
+in	O
+the	O
+range	O
+of	O
+2	O
+to	O
+4	O
+.	O
+
+These	O
+studies	O
+suggest	O
+that	O
+both	O
+phenacetin	B-Chemical
+and	O
+acetaminophen	B-Chemical
+may	O
+contribute	O
+to	O
+the	O
+burden	O
+of	O
+ESRD	B-Disease
+,	O
+with	O
+the	O
+risk	O
+of	O
+the	O
+latter	O
+being	O
+somewhat	O
+less	O
+than	O
+that	O
+of	O
+the	O
+former	O
+.	O
+
+This	O
+apparent	O
+difference	O
+in	O
+risk	O
+may	O
+not	O
+be	O
+due	O
+to	O
+differences	O
+in	O
+nephrotoxic	B-Disease
+potential	O
+of	O
+the	O
+drugs	O
+themselves	O
+.	O
+
+A	O
+lower	O
+relative	O
+risk	O
+would	O
+be	O
+expected	O
+for	O
+acetaminophen	B-Chemical
+if	O
+the	O
+risk	O
+of	O
+both	O
+drugs	O
+in	O
+combination	O
+with	O
+other	O
+analgesics	O
+was	O
+higher	O
+than	O
+the	O
+risk	O
+of	O
+either	O
+agent	O
+alone	O
+.	O
+
+Thus	O
+,	O
+acetaminophen	B-Chemical
+has	O
+been	O
+used	O
+both	O
+as	O
+a	O
+single	O
+agent	O
+and	O
+in	O
+combination	O
+with	O
+other	O
+analgesics	O
+,	O
+whereas	O
+phenacetin	B-Chemical
+was	O
+available	O
+only	O
+in	O
+combinations	O
+.	O
+
+The	O
+possibility	O
+that	O
+habitual	O
+use	O
+of	O
+acetaminophen	B-Chemical
+alone	O
+increases	O
+the	O
+risk	O
+of	O
+ESRD	B-Disease
+has	O
+not	O
+been	O
+clearly	O
+demonstrated	O
+,	O
+but	O
+cannot	O
+be	O
+dismissed	O
+.	O
+
+Acetaminophen	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+.	O
+
+Through	O
+30	O
+years	O
+of	O
+widespread	O
+use	O
+,	O
+acetaminophen	B-Chemical
+has	O
+been	O
+shown	O
+to	O
+be	O
+a	O
+remarkably	O
+safe	O
+medication	O
+in	O
+therapeutic	O
+dosages	O
+.	O
+
+The	O
+potential	O
+for	O
+acetaminophen	B-Chemical
+to	O
+produce	O
+cardiovascular	B-Disease
+toxicities	I-Disease
+is	O
+very	O
+low	O
+.	O
+
+However	O
+,	O
+acetaminophen	B-Chemical
+has	O
+been	O
+demonstrated	O
+to	O
+produce	O
+symptoms	O
+of	O
+anaphylaxis	B-Disease
+,	O
+including	O
+hypotension	B-Disease
+,	O
+in	O
+sensitive	O
+individuals	O
+.	O
+
+This	O
+article	O
+describes	O
+two	O
+critically	B-Disease
+ill	I-Disease
+patients	O
+in	O
+whom	O
+transient	O
+episodes	O
+of	O
+hypotension	B-Disease
+reproducibly	O
+developed	O
+after	O
+administration	O
+of	O
+acetaminophen	B-Chemical
+.	O
+
+Other	O
+symptoms	O
+of	O
+allergic	B-Disease
+reactions	I-Disease
+were	O
+not	O
+clinically	O
+detectable	O
+.	O
+
+The	O
+hypotensive	B-Disease
+episodes	O
+were	O
+severe	O
+enough	O
+to	O
+require	O
+vasopressor	O
+administration	O
+.	O
+
+The	O
+reports	O
+illustrate	O
+the	O
+need	O
+for	O
+clinicians	O
+to	O
+consider	O
+acetaminophen	B-Chemical
+in	O
+patients	O
+with	O
+hypotension	B-Disease
+of	O
+unknown	O
+origin	O
+.	O
+
+Reduction	O
+of	O
+heparan	B-Chemical
+sulphate	I-Chemical
+-	O
+associated	O
+anionic	O
+sites	O
+in	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+of	O
+rats	O
+with	O
+streptozotocin	B-Chemical
+-	O
+induced	O
+diabetic	B-Disease
+nephropathy	I-Disease
+.	O
+
+Heparan	B-Chemical
+sulphate	I-Chemical
+-	O
+associated	O
+anionic	O
+sites	O
+in	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+were	O
+studied	O
+in	O
+rats	O
+8	O
+months	O
+after	O
+induction	O
+of	O
+diabetes	B-Disease
+by	O
+streptozotocin	B-Chemical
+and	O
+in	O
+age	O
+-	O
+adn	O
+sex	O
+-	O
+matched	O
+control	O
+rats	O
+,	O
+employing	O
+the	O
+cationic	O
+dye	O
+cuprolinic	B-Chemical
+blue	I-Chemical
+.	O
+
+Morphometric	O
+analysis	O
+at	O
+the	O
+ultrastructural	O
+level	O
+was	O
+performed	O
+using	O
+a	O
+computerized	O
+image	O
+processor	O
+.	O
+
+The	O
+heparan	B-Chemical
+sulphate	I-Chemical
+specificity	O
+of	O
+the	O
+cuprolinic	B-Chemical
+blue	I-Chemical
+staining	O
+was	O
+demonstrated	O
+by	O
+glycosaminoglycan	B-Chemical
+-	O
+degrading	O
+enzymes	O
+,	O
+showing	O
+that	O
+pretreatment	O
+of	O
+the	O
+sections	O
+with	O
+heparitinase	O
+abolished	O
+all	O
+staining	O
+,	O
+whereas	O
+chondroitinase	O
+ABC	O
+had	O
+no	O
+effect	O
+.	O
+
+The	O
+majority	O
+of	O
+anionic	O
+sites	O
+(	O
+74	O
+%	O
+in	O
+diabetic	B-Disease
+and	O
+81	O
+%	O
+in	O
+control	O
+rats	O
+)	O
+were	O
+found	O
+within	O
+the	O
+lamina	O
+rara	O
+externa	O
+of	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+.	O
+
+A	O
+minority	O
+of	O
+anionic	O
+sites	O
+were	O
+scattered	O
+throughout	O
+the	O
+lamina	O
+densa	O
+and	O
+lamina	O
+rara	O
+interna	O
+,	O
+and	O
+were	O
+significantly	O
+smaller	O
+than	O
+those	O
+in	O
+the	O
+lamina	O
+rara	O
+externa	O
+of	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+and	O
+p	O
+<	O
+0	O
+.	O
+01	O
+for	O
+diabetic	B-Disease
+and	O
+control	O
+rats	O
+,	O
+respectively	O
+)	O
+.	O
+
+Diabetic	B-Disease
+rats	O
+progressively	O
+developed	O
+albuminuria	B-Disease
+reaching	O
+40	O
+.	O
+3	O
+(	O
+32	O
+.	O
+2	O
+-	O
+62	O
+.	O
+0	O
+)	O
+mg	O
+/	O
+24	O
+h	O
+after	O
+8	O
+months	O
+in	O
+contrast	O
+to	O
+the	O
+control	O
+animals	O
+(	O
+0	O
+.	O
+8	O
+(	O
+0	O
+.	O
+2	O
+-	O
+0	O
+.	O
+9	O
+)	O
+mg	O
+/	O
+24	O
+h	O
+,	O
+p	O
+<	O
+0	O
+.	O
+002	O
+)	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+,	O
+the	O
+number	O
+of	O
+heparan	B-Chemical
+sulphate	I-Chemical
+anionic	O
+sites	O
+and	O
+the	O
+total	O
+anionic	O
+site	O
+surface	O
+(	O
+number	O
+of	O
+anionic	O
+sites	O
+x	O
+mean	O
+anionic	O
+site	O
+surface	O
+)	O
+in	O
+the	O
+lamina	O
+rara	O
+externa	O
+of	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+was	O
+reduced	O
+by	O
+19	O
+%	O
+(	O
+p	O
+<	O
+0	O
+.	O
+021	O
+)	O
+and	O
+by	O
+26	O
+%	O
+(	O
+p	O
+<	O
+0	O
+.	O
+02	O
+)	O
+,	O
+respectively	O
+.	O
+
+Number	O
+and	O
+total	O
+anionic	O
+site	O
+surface	O
+in	O
+the	O
+remaining	O
+part	O
+of	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+(	O
+lamina	O
+densa	O
+and	O
+lamina	O
+rara	O
+interna	O
+)	O
+were	O
+not	O
+significantly	O
+changed	O
+.	O
+
+We	O
+conclude	O
+that	O
+in	O
+streptozotocin	B-Chemical
+-	O
+diabetic	B-Disease
+rats	O
+with	O
+an	O
+increased	O
+urinary	O
+albumin	O
+excretion	O
+,	O
+a	O
+reduced	O
+heparan	B-Chemical
+sulphate	I-Chemical
+charge	O
+barrier	O
+/	O
+density	O
+is	O
+found	O
+at	O
+the	O
+lamina	O
+rara	O
+externa	O
+of	O
+the	O
+glomerular	O
+basement	O
+membrane	O
+.	O
+
+Mediation	O
+of	O
+enhanced	O
+reflex	O
+vagal	O
+bradycardia	B-Disease
+by	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+via	O
+central	O
+dopamine	B-Chemical
+formation	O
+in	O
+dogs	O
+.	O
+
+L	B-Chemical
+-	I-Chemical
+Dopa	I-Chemical
+(	O
+5	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+decreased	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+after	O
+extracerebral	O
+decarboxylase	O
+inhibition	O
+with	O
+MK	B-Chemical
+-	I-Chemical
+486	I-Chemical
+(	O
+25	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+in	O
+anesthetize	O
+MAO	B-Chemical
+-	O
+inhibited	O
+dogs	O
+.	O
+
+In	O
+addition	O
+,	O
+reflex	O
+bradycardia	B-Disease
+caused	O
+by	O
+injected	O
+norepinephrine	B-Chemical
+was	O
+significantly	O
+enhanced	O
+by	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+,	O
+DL	B-Chemical
+-	I-Chemical
+Threo	I-Chemical
+-	I-Chemical
+dihydroxyphenylserine	I-Chemical
+had	O
+no	O
+effect	O
+on	O
+blood	O
+pressure	O
+,	O
+heart	O
+rate	O
+or	O
+reflex	O
+responses	O
+to	O
+norepinephrine	B-Chemical
+.	O
+
+FLA	B-Chemical
+-	I-Chemical
+63	I-Chemical
+,	O
+a	O
+dopamine	B-Chemical
+-	O
+beta	O
+-	O
+oxidase	O
+inhibitor	O
+,	O
+did	O
+not	O
+have	O
+any	O
+effect	O
+on	O
+the	O
+hypotension	B-Disease
+,	O
+bradycardia	B-Disease
+or	O
+reflex	O
+-	O
+enhancing	O
+effect	O
+of	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+.	O
+
+Pimozide	B-Chemical
+did	O
+not	O
+affect	O
+the	O
+actions	O
+of	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+on	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+but	O
+completely	O
+blocked	O
+the	O
+enhancement	O
+of	O
+reflexes	O
+.	O
+
+Removal	O
+of	O
+the	O
+carotid	O
+sinuses	O
+caused	O
+an	O
+elevation	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+and	O
+abolished	O
+the	O
+negative	O
+chronotropic	O
+effect	O
+of	O
+norepinephrine	B-Chemical
+.	O
+
+However	O
+,	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+restored	O
+the	O
+bradycardia	B-Disease
+caused	O
+by	O
+norepinephrine	B-Chemical
+in	O
+addition	O
+to	O
+decreasing	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+.	O
+
+5	B-Chemical
+-	I-Chemical
+HTP	I-Chemical
+(	O
+5	O
+mg	O
+/	O
+kg	O
+i	O
+.	O
+v	O
+.	O
+)	O
+decreased	O
+blood	O
+pressure	O
+and	O
+heart	O
+rate	O
+and	O
+decreased	O
+the	O
+reflex	O
+bradycardia	B-Disease
+to	O
+norepinephrine	B-Chemical
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+L	B-Chemical
+-	I-Chemical
+dopa	I-Chemical
+enhances	O
+reflex	O
+bradycardia	B-Disease
+through	O
+central	O
+alpha	O
+-	O
+receptor	O
+stimulation	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+effects	O
+are	O
+mediated	O
+through	O
+dopamine	B-Chemical
+rather	O
+than	O
+norepinephrine	B-Chemical
+and	O
+do	O
+not	O
+require	O
+the	O
+carotid	O
+sinus	O
+baroreceptors	O
+.	O
+
+Microangiopathic	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+complicating	O
+FK506	B-Chemical
+(	O
+tacrolimus	B-Chemical
+)	O
+therapy	O
+.	O
+
+We	O
+describe	O
+3	O
+episodes	O
+of	O
+microangiopathic	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+(	O
+MAHA	B-Disease
+)	O
+in	O
+2	O
+solid	O
+organ	O
+recipients	O
+under	O
+FK506	B-Chemical
+(	O
+tacrolimus	B-Chemical
+)	O
+therapy	O
+.	O
+
+In	O
+both	O
+cases	O
+,	O
+discontinuation	O
+of	O
+FK506	B-Chemical
+and	O
+treatment	O
+with	O
+plasma	O
+exchange	O
+,	O
+fresh	O
+frozen	O
+plasma	O
+replacement	O
+,	O
+corticosteroids	B-Chemical
+,	O
+aspirin	B-Chemical
+,	O
+and	O
+dipyridamole	B-Chemical
+led	O
+to	O
+resolution	O
+of	O
+MAHA	B-Disease
+.	O
+
+In	O
+one	O
+patient	O
+,	O
+reintroduction	O
+of	O
+FK506	B-Chemical
+led	O
+to	O
+rapid	O
+recurrence	O
+of	O
+MAHA	B-Disease
+.	O
+
+FK506	B-Chemical
+-	O
+associated	O
+MAHA	B-Disease
+is	O
+probably	O
+rare	O
+but	O
+physicians	O
+must	O
+be	O
+aware	O
+of	O
+this	O
+severe	O
+complication	O
+.	O
+
+In	O
+our	O
+experience	O
+and	O
+according	O
+to	O
+the	O
+literature	O
+,	O
+FK506	B-Chemical
+does	O
+not	O
+seem	O
+to	O
+cross	O
+-	O
+react	O
+with	O
+cyclosporin	B-Chemical
+A	I-Chemical
+(	O
+CyA	B-Chemical
+)	O
+,	O
+an	O
+immuno	O
+-	O
+suppressive	O
+drug	O
+already	O
+known	O
+to	O
+induce	O
+MAHA	B-Disease
+.	O
+
+Effect	O
+of	O
+some	O
+anticancer	O
+drugs	O
+and	O
+combined	O
+chemotherapy	O
+on	O
+renal	B-Disease
+toxicity	I-Disease
+.	O
+
+The	O
+nephrotoxic	B-Disease
+action	O
+of	O
+anticancer	O
+drugs	O
+such	O
+as	O
+nitrogranulogen	B-Chemical
+(	O
+NG	B-Chemical
+)	O
+,	O
+methotrexate	B-Chemical
+(	O
+MTX	B-Chemical
+)	O
+,	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+)	O
+and	O
+cyclophosphamide	B-Chemical
+(	O
+CY	B-Chemical
+)	O
+administered	O
+alone	O
+or	O
+in	O
+combination	O
+[	O
+MTX	B-Chemical
++	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
++	O
+CY	B-Chemical
+(	O
+CMF	O
+)	O
+]	O
+was	O
+evaluated	O
+in	O
+experiments	O
+on	O
+Wistar	O
+rats	O
+.	O
+
+After	O
+drug	O
+administration	O
+,	O
+creatinine	B-Chemical
+concentrations	O
+in	O
+the	O
+plasma	O
+and	O
+in	O
+the	O
+urine	O
+of	O
+the	O
+rats	O
+were	O
+determined	O
+,	O
+as	O
+well	O
+as	O
+creatinine	B-Chemical
+clearance	O
+.	O
+
+Histopathologic	O
+evaluation	O
+of	O
+the	O
+kidneys	O
+was	O
+also	O
+performed	O
+.	O
+
+After	O
+MTX	B-Chemical
+administration	O
+a	O
+significant	O
+increase	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0228	O
+)	O
+in	O
+the	O
+plasma	O
+creatinine	B-Chemical
+concentration	O
+and	O
+a	O
+significant	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0001	O
+)	O
+decrease	O
+in	O
+creatinine	B-Chemical
+clearance	O
+was	O
+noted	O
+compared	O
+to	O
+controls	O
+.	O
+
+After	O
+the	O
+administration	O
+of	O
+NG	B-Chemical
+,	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+and	O
+CY	B-Chemical
+neither	O
+a	O
+statistically	O
+significant	O
+increase	O
+in	O
+creatinine	B-Chemical
+concentration	O
+nor	O
+an	O
+increase	O
+in	O
+creatinine	B-Chemical
+clearance	O
+was	O
+observed	O
+compared	O
+to	O
+the	O
+group	O
+receiving	O
+no	O
+cytostatics	O
+.	O
+
+Following	O
+polytherapy	O
+according	O
+to	O
+the	O
+CMF	O
+regimen	O
+,	O
+a	O
+statistically	O
+significant	O
+decrease	O
+(	O
+p	O
+=	O
+0	O
+.	O
+0343	O
+)	O
+in	O
+creatinine	B-Chemical
+clearance	O
+was	O
+found	O
+,	O
+but	O
+creatinine	B-Chemical
+concentration	O
+did	O
+not	O
+increase	O
+significantly	O
+compared	O
+to	O
+controls	O
+.	O
+
+CY	B-Chemical
+caused	O
+hemorrhagic	B-Disease
+cystitis	I-Disease
+in	O
+40	O
+%	O
+of	O
+rats	O
+,	O
+but	O
+it	O
+did	O
+not	O
+cause	O
+this	O
+complication	O
+when	O
+combined	O
+with	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+and	O
+MTX	B-Chemical
+.	O
+
+Histologic	O
+changes	O
+were	O
+found	O
+in	O
+rat	O
+kidneys	O
+after	O
+administration	O
+of	O
+MTX	B-Chemical
+,	O
+CY	B-Chemical
+and	O
+NG	B-Chemical
+,	O
+while	O
+no	O
+such	O
+change	O
+was	O
+observed	O
+after	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+and	O
+joint	O
+administration	O
+of	O
+MTX	B-Chemical
++	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
++	O
+CY	B-Chemical
+compared	O
+to	O
+controls	O
+.	O
+
+Our	O
+studies	O
+indicate	O
+that	O
+nephrotoxicity	B-Disease
+of	O
+MTX	B-Chemical
++	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
++	O
+CY	B-Chemical
+administered	O
+jointly	O
+is	O
+lower	O
+than	O
+in	O
+monotherapy	O
+.	O
+
+The	O
+interpeduncular	O
+nucleus	O
+regulates	O
+nicotine	B-Chemical
+'	O
+s	O
+effects	O
+on	O
+free	O
+-	O
+field	O
+activity	O
+.	O
+
+Partial	O
+lesions	O
+were	O
+made	O
+with	O
+kainic	B-Chemical
+acid	I-Chemical
+in	O
+the	O
+interpeduncular	O
+nucleus	O
+of	O
+the	O
+ventral	O
+midbrain	O
+of	O
+the	O
+rat	O
+.	O
+
+Compared	O
+with	O
+sham	O
+-	O
+operated	O
+controls	O
+,	O
+lesions	O
+significantly	O
+(	O
+p	O
+<	O
+0	O
+.	O
+25	O
+)	O
+blunted	O
+the	O
+early	O
+(	O
+<	O
+60	O
+min	O
+)	O
+free	O
+-	O
+field	O
+locomotor	B-Disease
+hypoactivity	I-Disease
+caused	O
+by	O
+nicotine	B-Chemical
+(	O
+0	O
+.	O
+5	O
+mg	O
+kg	O
+(	O
+-	O
+1	O
+)	O
+,	O
+i	O
+.	O
+m	O
+.	O
+)	O
+,	O
+enhanced	O
+the	O
+later	O
+(	O
+60	O
+-	O
+120	O
+min	O
+)	O
+nicotine	B-Chemical
+-	O
+induced	O
+hyperactivity	B-Disease
+,	O
+and	O
+raised	O
+spontaneous	O
+nocturnal	O
+activity	O
+.	O
+
+Lesions	O
+reduced	O
+the	O
+extent	O
+of	O
+immunohistological	O
+staining	O
+for	O
+choline	B-Chemical
+acetyltransferase	O
+in	O
+the	O
+interpeduncular	O
+nucleus	O
+(	O
+p	O
+<	O
+0	O
+.	O
+025	O
+)	O
+,	O
+but	O
+not	O
+for	O
+tyrosine	B-Chemical
+hydroxylase	O
+in	O
+the	O
+surrounding	O
+catecholaminergic	O
+A10	O
+region	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+interpeduncular	O
+nucleus	O
+mediates	O
+nicotinic	O
+depression	B-Disease
+of	O
+locomotor	O
+activity	O
+and	O
+dampens	O
+nicotinic	O
+arousal	O
+mechanisms	O
+located	O
+elsewhere	O
+in	O
+the	O
+brain	O
+.	O
+
+Lithium	B-Chemical
+-	O
+associated	O
+cognitive	B-Disease
+and	I-Disease
+functional	I-Disease
+deficits	I-Disease
+reduced	O
+by	O
+a	O
+switch	O
+to	O
+divalproex	B-Chemical
+sodium	I-Chemical
+:	O
+a	O
+case	O
+series	O
+.	O
+
+BACKGROUND	O
+:	O
+Lithium	B-Chemical
+remains	O
+a	O
+first	O
+-	O
+line	O
+treatment	O
+for	O
+the	O
+acute	O
+and	O
+maintenance	O
+treatment	O
+of	O
+bipolar	B-Disease
+disorder	I-Disease
+.	O
+
+Although	O
+much	O
+has	O
+been	O
+written	O
+about	O
+the	O
+management	O
+of	O
+the	O
+more	O
+common	O
+adverse	O
+effects	O
+of	O
+lithium	B-Chemical
+,	O
+such	O
+as	O
+polyuria	B-Disease
+and	O
+tremor	B-Disease
+,	O
+more	O
+subtle	O
+lithium	B-Chemical
+side	O
+effects	O
+such	O
+as	O
+cognitive	B-Disease
+deficits	I-Disease
+,	O
+loss	B-Disease
+of	I-Disease
+creativity	I-Disease
+,	O
+and	O
+functional	B-Disease
+impairments	I-Disease
+remain	O
+understudied	O
+.	O
+
+This	O
+report	O
+summarizes	O
+our	O
+experience	O
+in	O
+switching	O
+bipolar	B-Disease
+patients	O
+from	O
+lithium	B-Chemical
+to	O
+divalproex	B-Chemical
+sodium	I-Chemical
+to	O
+alleviate	O
+such	O
+cognitive	B-Disease
+and	I-Disease
+functional	I-Disease
+impairments	I-Disease
+.	O
+
+METHOD	O
+:	O
+Open	O
+,	O
+case	O
+series	O
+design	O
+.	O
+
+RESULTS	O
+:	O
+We	O
+report	O
+seven	O
+cases	O
+where	O
+substitution	O
+of	O
+lithium	B-Chemical
+,	O
+either	O
+fully	O
+or	O
+partially	O
+,	O
+with	O
+divalproex	B-Chemical
+sodium	I-Chemical
+was	O
+extremely	O
+helpful	O
+in	O
+reducing	O
+the	O
+cognitive	B-Disease
+,	I-Disease
+motivational	I-Disease
+,	I-Disease
+or	I-Disease
+creative	I-Disease
+deficits	I-Disease
+attributed	O
+to	O
+lithium	B-Chemical
+in	O
+our	O
+bipolar	B-Disease
+patients	O
+.	O
+
+CONCLUSION	O
+:	O
+In	O
+this	O
+preliminary	O
+report	O
+,	O
+divalproex	B-Chemical
+sodium	I-Chemical
+was	O
+a	O
+superior	O
+alternative	O
+to	O
+lithium	B-Chemical
+in	O
+bipolar	B-Disease
+patients	O
+experiencing	O
+cognitive	B-Disease
+deficits	I-Disease
+,	O
+loss	B-Disease
+of	I-Disease
+creativity	I-Disease
+,	O
+and	O
+functional	B-Disease
+impairments	I-Disease
+.	O
+
+Effect	O
+of	O
+nifedipine	B-Chemical
+on	O
+renal	O
+function	O
+in	O
+liver	O
+transplant	O
+recipients	O
+receiving	O
+tacrolimus	B-Chemical
+.	O
+
+The	O
+effect	O
+of	O
+nifedipine	B-Chemical
+on	O
+renal	O
+function	O
+in	O
+liver	O
+transplant	O
+recipients	O
+who	O
+were	O
+receiving	O
+tacrolimus	B-Chemical
+was	O
+evaluated	O
+between	O
+January	O
+1992	O
+and	O
+January	O
+1996	O
+.	O
+
+Two	O
+groups	O
+of	O
+patients	O
+receiving	O
+tacrolimus	B-Chemical
+were	O
+compared	O
+over	O
+a	O
+period	O
+of	O
+1	O
+year	O
+,	O
+one	O
+group	O
+comprising	O
+hypertensive	B-Disease
+patients	O
+who	O
+were	O
+receiving	O
+nifedipine	B-Chemical
+,	O
+and	O
+the	O
+other	O
+comprising	O
+nonhypertensive	O
+patients	O
+not	O
+receiving	O
+nifedipine	B-Chemical
+.	O
+
+The	O
+time	O
+from	O
+transplant	O
+to	O
+baseline	O
+was	O
+similar	O
+in	O
+all	O
+patients	O
+.	O
+
+Nifedipine	B-Chemical
+significantly	O
+improved	O
+kidney	O
+function	O
+as	O
+indicated	O
+by	O
+a	O
+significant	O
+lowering	O
+of	O
+serum	O
+creatinine	B-Chemical
+levels	O
+at	O
+6	O
+and	O
+12	O
+months	O
+.	O
+
+The	O
+observed	O
+positive	O
+impact	O
+of	O
+nifedipine	B-Chemical
+on	O
+reducing	O
+the	O
+nephrotoxicity	B-Disease
+associated	O
+with	O
+tacrolimus	B-Chemical
+in	O
+liver	O
+transplant	O
+recipients	O
+should	O
+be	O
+an	O
+important	O
+factor	O
+in	O
+selecting	O
+an	O
+agent	O
+to	O
+treat	O
+hypertension	B-Disease
+in	O
+this	O
+population	O
+.	O
+
+Alpha	O
+and	O
+beta	O
+coma	B-Disease
+in	O
+drug	O
+intoxication	O
+uncomplicated	O
+by	O
+cerebral	B-Disease
+hypoxia	I-Disease
+.	O
+
+Four	O
+patients	O
+who	O
+were	O
+rendered	O
+comatose	B-Disease
+or	O
+stuporous	B-Disease
+by	O
+drug	O
+intoxication	O
+,	O
+but	O
+who	O
+were	O
+not	O
+hypoxic	O
+,	O
+are	O
+described	O
+.	O
+
+Three	O
+patients	O
+received	O
+high	O
+doses	O
+of	O
+chlormethiazole	B-Chemical
+for	O
+alcohol	B-Chemical
+withdrawal	B-Disease
+symptoms	I-Disease
+,	O
+and	O
+one	O
+took	O
+a	O
+suicidal	O
+overdose	B-Disease
+of	O
+nitrazepam	B-Chemical
+.	O
+
+The	O
+patient	O
+with	O
+nitrazepam	B-Chemical
+overdose	B-Disease
+and	O
+two	O
+of	O
+those	O
+with	O
+chlormethiazole	B-Chemical
+intoxication	O
+conformed	O
+to	O
+the	O
+criteria	O
+of	O
+'	O
+alpha	O
+coma	B-Disease
+'	O
+,	O
+showing	O
+non	O
+-	O
+reactive	O
+generalized	O
+or	O
+frontally	O
+predominant	O
+alpha	O
+activity	O
+in	O
+the	O
+EEG	O
+.	O
+
+The	O
+fourth	O
+patient	O
+who	O
+was	O
+unconscious	O
+after	O
+chlormethiazole	B-Chemical
+administration	O
+exhibite	O
+generalized	O
+non	O
+-	O
+reactive	O
+activity	O
+in	O
+the	O
+slow	O
+beta	O
+range	O
+.	O
+
+All	O
+four	O
+recovered	O
+completely	O
+without	O
+neurological	B-Disease
+sequelae	I-Disease
+following	O
+the	O
+withdrawal	O
+of	O
+the	O
+offending	O
+agents	O
+.	O
+
+The	O
+similarities	O
+between	O
+the	O
+effects	O
+of	O
+structural	O
+lesions	O
+and	O
+pharmacological	O
+depression	B-Disease
+of	O
+the	O
+brain	O
+stem	O
+reticular	O
+formation	O
+are	O
+discussed	O
+.	O
+
+It	O
+is	O
+suggested	O
+that	O
+in	O
+both	O
+situations	O
+disturbed	O
+reticulo	O
+-	O
+thalamic	O
+interactions	O
+are	O
+important	O
+in	O
+the	O
+pathogenesis	O
+of	O
+alpha	O
+coma	B-Disease
+.	O
+
+It	O
+is	O
+concluded	O
+that	O
+when	O
+this	O
+electroencephalographic	O
+and	O
+behavioural	O
+picture	O
+is	O
+seen	O
+in	O
+drug	O
+intoxication	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+significant	O
+hypoxaemia	B-Disease
+,	O
+a	O
+favourable	O
+outcome	O
+may	O
+be	O
+anticipated	O
+.	O
+
+Magnetic	O
+resonance	O
+volumetry	O
+of	O
+the	O
+cerebellum	O
+in	O
+epileptic	B-Disease
+patients	O
+after	O
+phenytoin	B-Chemical
+overdosages	B-Disease
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+evaluate	O
+the	O
+relationship	O
+between	O
+phenytoin	B-Chemical
+medication	O
+and	O
+cerebellar	B-Disease
+atrophy	I-Disease
+in	O
+patients	O
+who	O
+had	O
+experienced	O
+clinical	O
+intoxication	O
+.	O
+
+Five	O
+females	O
+and	O
+6	O
+males	O
+,	O
+21	O
+-	O
+59	O
+years	O
+of	O
+age	O
+,	O
+were	O
+examined	O
+with	O
+a	O
+1	O
+.	O
+5	O
+-	O
+T	O
+whole	O
+-	O
+body	O
+system	O
+using	O
+a	O
+circular	O
+polarized	O
+head	O
+coil	O
+.	O
+
+Conventional	O
+spin	O
+echo	O
+images	O
+were	O
+acquired	O
+in	O
+the	O
+sagittal	O
+and	O
+transverse	O
+orientation	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+performed	O
+a	O
+high	O
+-	O
+resolution	O
+3D	O
+gradient	O
+echo	O
+,	O
+T1	O
+-	O
+weighted	O
+sequences	O
+at	O
+a	O
+1	O
+-	O
+mm	O
+slice	O
+thickness	O
+.	O
+
+The	O
+images	O
+were	O
+subsequently	O
+processed	O
+to	O
+obtain	O
+volumetric	O
+data	O
+for	O
+the	O
+cerebellum	O
+.	O
+
+Cerebellar	O
+volume	O
+for	O
+the	O
+patient	O
+group	O
+ranged	O
+between	O
+67	O
+.	O
+66	O
+and	O
+131	O
+.	O
+08	O
+ml	O
+(	O
+mean	O
+108	O
+.	O
+9	O
+ml	O
+)	O
+.	O
+
+In	O
+addition	O
+3D	O
+gradient	O
+echo	O
+data	O
+sets	O
+from	O
+10	O
+healthy	O
+male	O
+and	O
+10	O
+healthy	O
+female	O
+age	O
+-	O
+matched	O
+volunteers	O
+were	O
+used	O
+to	O
+compare	O
+cerebellar	O
+volumes	O
+.	O
+
+Using	O
+linear	O
+regression	O
+we	O
+found	O
+that	O
+no	O
+correlation	O
+exists	O
+between	O
+seizure	B-Disease
+duration	O
+,	O
+elevation	O
+of	O
+phenytoin	B-Chemical
+serum	O
+levels	O
+and	O
+cerebellar	O
+volume	O
+.	O
+
+However	O
+,	O
+multiple	O
+regression	O
+for	O
+the	O
+daily	O
+dosage	O
+,	O
+duration	O
+of	O
+phenytoin	B-Chemical
+treatment	O
+and	O
+cerebellar	O
+volume	O
+revealed	O
+a	O
+correlation	O
+of	O
+these	O
+parameters	O
+.	O
+
+We	O
+conclude	O
+that	O
+phenytoin	B-Chemical
+overdosage	B-Disease
+does	O
+not	O
+necessarily	O
+result	O
+in	O
+cerebellar	B-Disease
+atrophy	I-Disease
+and	O
+it	O
+is	O
+unlikely	O
+that	O
+phenytoin	B-Chemical
+medication	O
+was	O
+the	O
+only	O
+cause	O
+of	O
+cerebellar	B-Disease
+atrophy	I-Disease
+in	O
+the	O
+remaining	O
+patients	O
+.	O
+
+Quantitative	O
+morphometric	O
+studies	O
+of	O
+the	O
+cerebellum	O
+provide	O
+valuable	O
+insights	O
+into	O
+the	O
+pathogenesis	O
+of	O
+cerebellar	B-Disease
+disorders	I-Disease
+.	O
+
+Late	O
+recovery	O
+of	O
+renal	O
+function	O
+in	O
+a	O
+woman	O
+with	O
+the	O
+hemolytic	B-Disease
+uremic	I-Disease
+syndrome	I-Disease
+.	O
+
+A	O
+case	O
+is	O
+reported	O
+of	O
+the	O
+hemolytic	B-Disease
+uremic	I-Disease
+syndrome	I-Disease
+(	O
+HUS	B-Disease
+)	O
+in	O
+a	O
+woman	O
+taking	O
+oral	B-Chemical
+contraceptives	I-Chemical
+.	O
+
+She	O
+was	O
+treated	O
+with	O
+heparin	B-Chemical
+,	O
+dipyridamole	B-Chemical
+and	O
+hemodialysis	O
+;	O
+and	O
+after	O
+more	O
+than	O
+three	O
+months	O
+,	O
+her	O
+urinary	O
+output	O
+rose	O
+above	O
+500	O
+ml	O
+;	O
+and	O
+six	O
+months	O
+after	O
+the	O
+onset	O
+of	O
+anuria	B-Disease
+,	O
+dialysis	O
+treatment	O
+was	O
+stopped	O
+.	O
+
+This	O
+case	O
+emphasizes	O
+the	O
+possibility	O
+that	O
+HUS	B-Disease
+in	O
+adults	O
+is	O
+not	O
+invariably	O
+irreversible	O
+and	O
+that	O
+,	O
+despite	O
+prolonged	O
+oliguria	B-Disease
+,	O
+recovery	O
+of	O
+renal	O
+function	O
+can	O
+be	O
+obtained	O
+.	O
+
+Therefore	O
+,	O
+in	O
+adult	O
+patients	O
+affected	O
+by	O
+HUS	B-Disease
+,	O
+dialysis	O
+should	O
+not	O
+be	O
+discontinued	O
+prematurely	O
+;	O
+moreover	O
+,	O
+bilateral	O
+nephrectomy	O
+,	O
+for	O
+treatment	O
+of	O
+severe	O
+hypertension	B-Disease
+and	O
+microangiopathic	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+,	O
+should	O
+be	O
+performed	O
+with	O
+caution	O
+.	O
+
+Morphological	O
+features	O
+of	O
+encephalopathy	B-Disease
+after	O
+chronic	O
+administration	O
+of	O
+the	O
+antiepileptic	O
+drug	O
+valproate	B-Chemical
+to	O
+rats	O
+.	O
+
+A	O
+transmission	O
+electron	O
+microscopic	O
+study	O
+of	O
+capillaries	O
+in	O
+the	O
+cerebellar	O
+cortex	O
+.	O
+
+Long	O
+-	O
+term	O
+intragastric	O
+application	O
+of	O
+the	O
+antiepileptic	O
+drug	O
+sodium	B-Chemical
+valproate	I-Chemical
+(	O
+Vupral	O
+"	O
+Polfa	O
+"	O
+)	O
+at	O
+the	O
+effective	O
+dose	O
+of	O
+200	O
+mg	O
+/	O
+kg	O
+b	O
+.	O
+
+w	O
+.	O
+once	O
+daily	O
+to	O
+rats	O
+for	O
+1	O
+,	O
+3	O
+,	O
+6	O
+,	O
+9	O
+and	O
+12	O
+months	O
+revealed	O
+neurological	B-Disease
+disorders	I-Disease
+indicating	O
+cerebellum	B-Disease
+damage	I-Disease
+(	O
+"	O
+valproate	B-Chemical
+encephalopathy	B-Disease
+"	O
+)	O
+.	O
+
+The	O
+first	O
+ultrastructural	O
+changes	O
+in	O
+structural	O
+elements	O
+of	O
+the	O
+blood	O
+-	O
+brain	O
+-	O
+barrier	O
+(	O
+BBB	O
+)	O
+in	O
+the	O
+cerebellar	O
+cortex	O
+were	O
+detectable	O
+after	O
+3	O
+months	O
+of	O
+the	O
+experiment	O
+.	O
+
+They	O
+became	O
+more	O
+severe	O
+in	O
+the	O
+later	O
+months	O
+of	O
+the	O
+experiment	O
+,	O
+and	O
+were	O
+most	O
+severe	O
+after	O
+12	O
+months	O
+,	O
+located	O
+mainly	O
+in	O
+the	O
+molecular	O
+layer	O
+of	O
+the	O
+cerebellar	O
+cortex	O
+.	O
+
+Lesions	O
+of	O
+the	O
+capillary	O
+included	O
+necrosis	B-Disease
+of	O
+endothelial	O
+cells	O
+.	O
+
+Organelles	O
+of	O
+these	O
+cells	O
+,	O
+in	O
+particular	O
+the	O
+mitochondria	O
+(	O
+increased	O
+number	O
+and	O
+size	O
+,	O
+distinct	O
+degeneration	O
+of	O
+their	O
+matrix	O
+and	O
+cristae	O
+)	O
+and	O
+Golgi	O
+apparatus	O
+were	O
+altered	O
+.	O
+
+Reduced	O
+size	O
+of	O
+capillary	O
+lumen	O
+and	O
+occlusion	O
+were	O
+caused	O
+by	O
+swollen	O
+endothelial	O
+cells	O
+which	O
+had	O
+luminal	B-Chemical
+protrusions	O
+and	O
+swollen	O
+microvilli	O
+.	O
+
+Pressure	O
+on	O
+the	O
+vessel	O
+wall	O
+was	O
+produced	O
+by	O
+enlarged	O
+perivascular	O
+astrocytic	O
+processes	O
+.	O
+
+Fragments	O
+of	O
+necrotic	B-Disease
+endothelial	O
+cells	O
+were	O
+in	O
+the	O
+vascular	O
+lumens	O
+and	O
+in	O
+these	O
+there	O
+was	O
+loosening	O
+and	O
+breaking	O
+of	O
+tight	O
+cellular	O
+junctions	O
+.	O
+
+Damage	O
+to	O
+the	O
+vascular	O
+basement	O
+lamina	O
+was	O
+also	O
+observed	O
+.	O
+
+Damage	O
+to	O
+the	O
+capillary	O
+was	O
+accompanied	O
+by	O
+marked	O
+damage	O
+to	O
+neuroglial	O
+cells	O
+,	O
+mainly	O
+to	O
+perivascular	O
+processes	O
+of	O
+astrocytes	O
+.	O
+
+The	O
+proliferation	O
+of	O
+astrocytes	O
+(	O
+Bergmann	O
+'	O
+s	O
+in	O
+particular	O
+)	O
+and	O
+occasionally	O
+of	O
+oligodendrocytes	O
+was	O
+found	O
+.	O
+
+Alterations	O
+in	O
+the	O
+structural	O
+elements	O
+of	O
+the	O
+BBB	O
+coexisted	O
+with	O
+marked	O
+lesions	O
+of	O
+neurons	O
+of	O
+the	O
+cerebellum	O
+(	O
+Purkinje	O
+cells	O
+are	O
+earliest	O
+)	O
+.	O
+
+In	O
+electron	O
+micrographs	O
+both	O
+luminal	B-Chemical
+and	O
+antiluminal	O
+sides	O
+of	O
+the	O
+BBB	O
+of	O
+the	O
+cerebellar	O
+cortex	O
+had	O
+similar	O
+lesions	O
+.	O
+
+The	O
+possible	O
+influence	O
+of	O
+the	O
+hepatic	B-Disease
+damage	I-Disease
+,	O
+mainly	O
+hyperammonemia	B-Disease
+,	O
+upon	O
+the	O
+development	O
+of	O
+valproate	B-Chemical
+encephalopathy	B-Disease
+is	O
+discussed	O
+.	O
+
+Fatal	O
+intracranial	B-Disease
+bleeding	I-Disease
+associated	O
+with	O
+prehospital	O
+use	O
+of	O
+epinephrine	B-Chemical
+.	O
+
+We	O
+present	O
+a	O
+case	O
+of	O
+paramedic	O
+misjudgment	O
+in	O
+the	O
+execution	O
+of	O
+a	O
+protocol	O
+for	O
+the	O
+treatment	O
+of	O
+allergic	B-Disease
+reaction	I-Disease
+in	O
+a	O
+case	O
+of	O
+pulmonary	B-Disease
+edema	I-Disease
+with	O
+wheezing	B-Disease
+.	O
+
+The	O
+sudden	O
+onset	O
+of	O
+respiratory	B-Disease
+distress	I-Disease
+,	O
+rash	B-Disease
+,	O
+and	O
+a	O
+history	O
+of	O
+a	O
+new	O
+medicine	O
+led	O
+the	O
+two	O
+paramedics	O
+on	O
+the	O
+scene	O
+to	O
+administer	O
+subcutaneous	O
+epinephrine	B-Chemical
+.	O
+
+Subsequently	O
+,	O
+acute	O
+cardiac	B-Disease
+arrest	I-Disease
+and	O
+fatal	O
+subarachnoid	B-Disease
+hemorrhage	I-Disease
+occurred	O
+.	O
+
+Epinephrine	B-Chemical
+has	O
+a	O
+proven	O
+role	O
+in	O
+cardiac	B-Disease
+arrest	I-Disease
+in	O
+prehospital	O
+care	O
+;	O
+however	O
+,	O
+use	O
+by	O
+paramedics	O
+in	O
+patients	O
+with	O
+suspected	O
+allergic	B-Disease
+reaction	I-Disease
+and	O
+severe	O
+hypertension	B-Disease
+should	O
+be	O
+viewed	O
+with	O
+caution	O
+.	O
+
+Role	O
+of	O
+activation	O
+of	O
+bradykinin	B-Chemical
+B2	O
+receptors	O
+in	O
+disruption	O
+of	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+during	O
+acute	O
+hypertension	B-Disease
+.	O
+
+Cellular	O
+mechanisms	O
+which	O
+account	O
+for	O
+disruption	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+during	O
+acute	O
+hypertension	B-Disease
+are	O
+not	O
+clear	O
+.	O
+
+The	O
+goal	O
+of	O
+this	O
+study	O
+was	O
+to	O
+determine	O
+the	O
+role	O
+of	O
+synthesis	O
+/	O
+release	O
+of	O
+bradykinin	B-Chemical
+to	O
+activate	O
+B2	O
+receptors	O
+in	O
+disruption	O
+of	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+during	O
+acute	O
+hypertension	B-Disease
+.	O
+
+Permeability	O
+of	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+was	O
+quantitated	O
+by	O
+clearance	O
+of	O
+fluorescent	O
+-	O
+labeled	O
+dextran	B-Chemical
+before	O
+and	O
+during	O
+phenylephrine	B-Chemical
+-	O
+induced	O
+acute	O
+hypertension	B-Disease
+in	O
+rats	O
+treated	O
+with	O
+vehicle	O
+and	O
+Hoe	B-Chemical
+-	I-Chemical
+140	I-Chemical
+(	O
+0	O
+.	O
+1	O
+microM	O
+)	O
+.	O
+
+Phenylephrine	B-Chemical
+infusion	O
+increased	O
+arterial	O
+pressure	O
+,	O
+arteriolar	O
+diameter	O
+and	O
+clearance	O
+of	O
+fluorescent	O
+dextran	B-Chemical
+by	O
+a	O
+similar	O
+magnitude	O
+in	O
+both	O
+groups	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+disruption	O
+of	O
+the	O
+blood	O
+-	O
+brain	O
+barrier	O
+during	O
+acute	O
+hypertension	B-Disease
+is	O
+not	O
+related	O
+to	O
+the	O
+synthesis	O
+/	O
+release	O
+of	O
+bradykinin	B-Chemical
+to	O
+activate	O
+B2	O
+receptors	O
+.	O
+
+Risk	O
+factors	O
+of	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+in	O
+preterm	O
+infants	O
+.	O
+
+Among	O
+547	O
+preterm	O
+infants	O
+of	O
+<	O
+or	O
+=	O
+34	O
+weeks	O
+gestation	O
+born	O
+between	O
+1987	O
+and	O
+1991	O
+,	O
+8	O
+children	O
+(	O
+1	O
+.	O
+46	O
+%	O
+)	O
+developed	O
+severe	O
+progressive	O
+and	O
+bilateral	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+.	O
+
+Perinatal	O
+risk	O
+factors	O
+of	O
+infants	O
+with	O
+hearing	B-Disease
+loss	I-Disease
+were	O
+compared	O
+with	O
+those	O
+of	O
+two	O
+control	O
+groups	O
+matched	O
+for	O
+gestation	O
+and	O
+birth	O
+weight	O
+and	O
+for	O
+perinatal	O
+complications	O
+.	O
+
+Our	O
+observations	O
+demonstrated	O
+an	O
+association	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+with	O
+a	O
+higher	O
+incidence	O
+of	O
+perinatal	O
+complications	O
+.	O
+
+Ototoxicity	B-Disease
+appeared	O
+closely	O
+related	O
+to	O
+a	O
+prolonged	O
+administration	O
+and	O
+higher	O
+total	O
+dose	O
+of	O
+ototoxic	B-Disease
+drugs	O
+,	O
+particularly	O
+aminoglycosides	B-Chemical
+and	O
+furosemide	B-Chemical
+.	O
+
+Finally	O
+,	O
+we	O
+strongly	O
+recommend	O
+to	O
+prospectively	O
+and	O
+regularly	O
+perform	O
+audiologic	O
+assessment	O
+in	O
+sick	O
+preterm	O
+children	O
+as	O
+hearing	B-Disease
+loss	I-Disease
+is	O
+of	O
+delayed	O
+onset	O
+and	O
+in	O
+most	O
+cases	O
+bilateral	O
+and	O
+severe	O
+.	O
+
+Seizure	B-Disease
+resulting	O
+from	O
+a	O
+venlafaxine	B-Chemical
+overdose	B-Disease
+.	O
+
+OBJECTIVE	O
+:	O
+To	O
+report	O
+a	O
+case	O
+of	O
+venlafaxine	B-Chemical
+overdose	B-Disease
+.	O
+
+CASE	O
+SUMMARY	O
+:	O
+A	O
+40	O
+-	O
+year	O
+-	O
+old	O
+woman	O
+with	O
+major	B-Disease
+depression	I-Disease
+took	O
+an	O
+overdose	B-Disease
+of	O
+venlafaxine	B-Chemical
+in	O
+an	O
+apparent	O
+suicide	O
+attempt	O
+.	O
+
+After	O
+the	O
+ingestion	O
+of	O
+26	O
+venlafaxine	B-Chemical
+50	O
+-	O
+mg	O
+tablets	O
+,	O
+the	O
+patient	O
+experienced	O
+a	O
+witnessed	O
+generalized	O
+seizure	B-Disease
+.	O
+
+She	O
+was	O
+admitted	O
+to	O
+the	O
+medical	O
+intensive	O
+care	O
+unit	O
+,	O
+venlafaxine	B-Chemical
+was	O
+discontinued	O
+,	O
+and	O
+no	O
+further	O
+sequelae	O
+were	O
+seen	O
+.	O
+
+DISCUSSION	O
+:	O
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+reported	O
+case	O
+of	O
+venlafaxine	B-Chemical
+overdose	B-Disease
+that	O
+resulted	O
+in	O
+a	O
+generalized	O
+seizure	B-Disease
+.	O
+
+Based	O
+on	O
+nonoverdose	O
+pharmacokinetics	O
+and	O
+pharmacodynamics	O
+of	O
+venlafaxine	B-Chemical
+and	O
+the	O
+potential	O
+risks	O
+of	O
+available	O
+interventions	O
+,	O
+no	O
+emergent	O
+therapy	O
+was	O
+instituted	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+venlafaxine	B-Chemical
+overdose	B-Disease
+in	O
+our	O
+patient	O
+resulted	O
+in	O
+a	O
+single	O
+episode	O
+of	O
+generalized	O
+seizure	B-Disease
+but	O
+elicited	O
+no	O
+further	O
+sequelae	O
+.	O
+
+Combined	O
+effects	O
+of	O
+prolonged	O
+prostaglandin	B-Chemical
+E1	I-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+and	O
+haemodilution	B-Disease
+on	O
+human	O
+hepatic	O
+function	O
+.	O
+
+Combined	O
+effects	O
+of	O
+prolonged	O
+prostaglandin	B-Chemical
+E1	I-Chemical
+(	O
+PGE1	B-Chemical
+)	O
+-	O
+induced	O
+hypotension	B-Disease
+and	O
+haemodilution	B-Disease
+on	O
+hepatic	O
+function	O
+were	O
+studied	O
+in	O
+30	O
+patients	O
+undergoing	O
+hip	O
+surgery	O
+.	O
+
+The	O
+patients	O
+were	O
+randomly	O
+allocated	O
+to	O
+one	O
+of	O
+three	O
+groups	O
+;	O
+those	O
+in	O
+group	O
+A	O
+(	O
+n	O
+=	O
+10	O
+)	O
+were	O
+subjected	O
+to	O
+controlled	O
+hypotension	B-Disease
+alone	O
+,	O
+those	O
+in	O
+group	O
+B	O
+(	O
+n	O
+=	O
+10	O
+)	O
+to	O
+haemodilution	B-Disease
+alone	O
+and	O
+those	O
+in	O
+group	O
+C	O
+(	O
+n	O
+=	O
+10	O
+)	O
+to	O
+both	O
+controlled	O
+hypotension	B-Disease
+and	O
+haemodilution	B-Disease
+.	O
+
+Haemodilution	B-Disease
+in	O
+groups	O
+B	O
+and	O
+C	O
+was	O
+produced	O
+by	O
+withdrawing	O
+approximately	O
+1000	O
+mL	O
+of	O
+blood	O
+and	O
+replacing	O
+it	O
+with	O
+the	O
+same	O
+amount	O
+of	O
+dextran	B-Chemical
+solution	O
+,	O
+and	O
+final	O
+haematocrit	O
+values	O
+were	O
+21	O
+or	O
+22	O
+%	O
+.	O
+
+Controlled	O
+hypotension	B-Disease
+in	O
+groups	O
+A	O
+and	O
+C	O
+was	O
+induced	O
+with	O
+PGE1	B-Chemical
+to	O
+maintain	O
+mean	O
+arterial	O
+blood	O
+pressure	O
+at	O
+55	O
+mmHg	O
+for	O
+180	O
+min	O
+.	O
+
+Measurements	O
+included	O
+arterial	O
+ketone	O
+body	O
+ratio	O
+(	O
+AKBR	O
+,	O
+aceto	B-Chemical
+-	I-Chemical
+acetate	I-Chemical
+/	O
+3	B-Chemical
+-	I-Chemical
+hydroxybutyrate	I-Chemical
+)	O
+and	O
+clinical	O
+hepatic	O
+function	O
+parameters	O
+.	O
+
+AKBR	O
+and	O
+biological	O
+hepatic	O
+function	O
+tests	O
+showed	O
+no	O
+change	O
+throughout	O
+the	O
+time	O
+course	O
+in	O
+groups	O
+A	O
+and	O
+B	O
+.	O
+
+In	O
+group	O
+C	O
+,	O
+AKBR	O
+showed	O
+a	O
+significant	O
+decrease	O
+at	O
+120	O
+min	O
+(	O
+-	O
+40	O
+%	O
+)	O
+and	O
+at	O
+180	O
+min	O
+(	O
+-	O
+49	O
+%	O
+)	O
+after	O
+the	O
+start	O
+of	O
+hypotension	B-Disease
+and	O
+at	O
+60	O
+min	O
+(	O
+-	O
+32	O
+%	O
+)	O
+after	O
+recovery	O
+of	O
+normotension	O
+,	O
+and	O
+SGOT	O
+,	O
+SGPT	O
+,	O
+LDH	O
+and	O
+total	O
+bilirubin	B-Chemical
+showed	O
+significant	O
+increases	O
+after	O
+operation	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+a	O
+prolonged	O
+combination	O
+of	O
+more	O
+than	O
+120	O
+min	O
+of	O
+PGE1	B-Chemical
+-	O
+induced	O
+hypotension	B-Disease
+and	O
+moderate	O
+haemodilution	B-Disease
+would	O
+cause	O
+impairment	B-Disease
+of	I-Disease
+hepatic	I-Disease
+function	I-Disease
+.	O
+
+Cardiovascular	B-Disease
+alterations	I-Disease
+in	O
+rat	O
+fetuses	O
+exposed	O
+to	O
+calcium	B-Chemical
+channel	O
+blockers	O
+.	O
+
+Preclinical	O
+toxicologic	O
+investigation	O
+suggested	O
+that	O
+a	O
+new	O
+calcium	B-Chemical
+channel	O
+blocker	O
+,	O
+Ro	B-Chemical
+40	I-Chemical
+-	I-Chemical
+5967	I-Chemical
+,	O
+induced	O
+cardiovascular	B-Disease
+alterations	I-Disease
+in	O
+rat	O
+fetuses	O
+exposed	O
+to	O
+this	O
+agent	O
+during	O
+organogenesis	O
+.	O
+
+The	O
+present	O
+study	O
+was	O
+designed	O
+to	O
+investigate	O
+the	O
+hypothesis	O
+that	O
+calcium	B-Chemical
+channel	O
+blockers	O
+in	O
+general	O
+induce	O
+cardiovascular	B-Disease
+malformations	I-Disease
+indicating	O
+a	O
+pharmacologic	O
+class	O
+effect	O
+.	O
+
+We	O
+studied	O
+three	O
+calcium	B-Chemical
+channel	O
+blockers	O
+of	O
+different	O
+structure	O
+,	O
+nifedipine	B-Chemical
+,	O
+diltiazem	B-Chemical
+,	O
+and	O
+verapamil	B-Chemical
+,	O
+along	O
+with	O
+the	O
+new	O
+agent	O
+.	O
+
+Pregnant	O
+rats	O
+were	O
+administered	O
+one	O
+of	O
+these	O
+calcium	B-Chemical
+channel	O
+blockers	O
+during	O
+the	O
+period	O
+of	O
+cardiac	O
+morphogenesis	O
+and	O
+the	O
+offspring	O
+examined	O
+on	O
+day	O
+20	O
+of	O
+gestation	O
+for	O
+cardiovascular	B-Disease
+malformations	I-Disease
+.	O
+
+A	O
+low	O
+incidence	O
+of	O
+cardiovascular	B-Disease
+malformations	I-Disease
+was	O
+observed	O
+after	O
+exposure	O
+to	O
+each	O
+of	O
+the	O
+four	O
+calcium	B-Chemical
+channel	O
+blockers	O
+,	O
+but	O
+this	O
+incidence	O
+was	O
+statistically	O
+significant	O
+only	O
+for	O
+verapamil	B-Chemical
+and	O
+nifedipine	B-Chemical
+.	O
+
+All	O
+four	O
+agents	O
+were	O
+associated	O
+with	O
+aortic	O
+arch	O
+branching	O
+variants	O
+,	O
+although	O
+significantly	O
+increased	O
+only	O
+for	O
+Ro	B-Chemical
+40	I-Chemical
+-	I-Chemical
+5967	I-Chemical
+and	O
+verapamil	B-Chemical
+.	O
+
+The	O
+site	O
+of	O
+common	O
+side	O
+effects	O
+of	O
+sumatriptan	B-Chemical
+.	O
+
+Atypical	B-Disease
+sensations	I-Disease
+following	O
+the	O
+use	O
+of	O
+subcutaneous	O
+sumatriptan	B-Chemical
+are	O
+common	O
+,	O
+but	O
+of	O
+uncertain	O
+origin	O
+.	O
+
+They	O
+are	O
+almost	O
+always	O
+benign	O
+,	O
+but	O
+can	O
+be	O
+mistaken	O
+for	O
+a	O
+serious	O
+adverse	O
+event	O
+by	O
+the	O
+patient	O
+.	O
+
+Two	O
+patients	O
+are	O
+presented	O
+with	O
+tingling	B-Disease
+or	I-Disease
+burning	I-Disease
+sensations	I-Disease
+limited	O
+to	O
+areas	O
+of	O
+heat	O
+exposure	O
+or	O
+sunburn	B-Disease
+.	O
+
+In	O
+these	O
+individuals	O
+,	O
+side	O
+effects	O
+are	O
+most	O
+likely	O
+generated	O
+superficially	O
+in	O
+the	O
+skin	O
+.	O
+
+Macula	O
+toxicity	B-Disease
+after	O
+intravitreal	O
+amikacin	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+Although	O
+intravitreal	O
+aminoglycosides	B-Chemical
+have	O
+substantially	O
+improved	O
+visual	O
+prognosis	O
+in	O
+endophthalmitis	B-Disease
+,	O
+macular	O
+infarction	B-Disease
+may	O
+impair	O
+full	O
+visual	O
+recovery	O
+.	O
+
+METHODS	O
+:	O
+We	O
+present	O
+a	O
+case	O
+of	O
+presumed	O
+amikacin	B-Chemical
+retinal	B-Disease
+toxicity	I-Disease
+following	O
+treatment	O
+with	O
+amikacin	B-Chemical
+and	O
+vancomycin	B-Chemical
+for	O
+alpha	O
+-	O
+haemolytic	O
+streptococcal	B-Disease
+endophthalmitis	I-Disease
+.	O
+
+RESULTS	O
+:	O
+Endophthalmitis	B-Disease
+resolved	O
+with	O
+improvement	O
+in	O
+visual	O
+acuity	O
+to	O
+6	O
+/	O
+24	O
+at	O
+three	O
+months	O
+.	O
+
+Fundus	O
+fluorescein	B-Chemical
+angiography	O
+confirmed	O
+macular	O
+capillary	O
+closure	O
+and	O
+telangiectasis	B-Disease
+.	O
+
+CONCLUSIONS	O
+:	O
+Currently	O
+accepted	O
+intravitreal	O
+antibiotic	O
+regimens	O
+may	O
+cause	O
+retinal	B-Disease
+toxicity	I-Disease
+and	O
+macular	O
+ischaemia	B-Disease
+.	O
+
+Treatment	O
+strategies	O
+aimed	O
+at	O
+avoiding	O
+retinal	B-Disease
+toxicity	I-Disease
+are	O
+discussed	O
+.	O
+
+The	O
+role	O
+of	O
+nicotine	B-Chemical
+in	O
+smoking	O
+-	O
+related	O
+cardiovascular	B-Disease
+disease	I-Disease
+.	O
+
+Nicotine	B-Chemical
+activates	O
+the	O
+sympathetic	O
+nervous	O
+system	O
+and	O
+in	O
+this	O
+way	O
+could	O
+contribute	O
+to	O
+cardiovascular	B-Disease
+disease	I-Disease
+.	O
+
+Animal	O
+studies	O
+and	O
+mechanistic	O
+studies	O
+indicate	O
+that	O
+nicotine	B-Chemical
+could	O
+play	O
+a	O
+role	O
+in	O
+accelerating	O
+atherosclerosis	B-Disease
+,	O
+but	O
+evidence	O
+among	O
+humans	O
+is	O
+too	O
+inadequate	O
+to	O
+be	O
+definitive	O
+about	O
+such	O
+an	O
+effect	O
+.	O
+
+Almost	O
+certainly	O
+,	O
+nicotine	B-Chemical
+via	O
+its	O
+hemodynamic	O
+effects	O
+contributes	O
+to	O
+acute	O
+cardiovascular	O
+events	O
+,	O
+although	O
+current	O
+evidence	O
+suggests	O
+that	O
+the	O
+effects	O
+of	O
+nicotine	B-Chemical
+are	O
+much	O
+less	O
+important	O
+than	O
+are	O
+the	O
+prothrombotic	O
+effects	O
+of	O
+cigarette	O
+smoking	O
+or	O
+the	O
+effects	O
+of	O
+carbon	B-Chemical
+monoxide	I-Chemical
+.	O
+
+Nicotine	B-Chemical
+does	O
+not	O
+appear	O
+to	O
+enhance	O
+thrombosis	B-Disease
+among	O
+humans	O
+.	O
+
+Clinical	O
+studies	O
+of	O
+pipe	O
+smokers	O
+and	O
+people	O
+using	O
+transdermal	O
+nicotine	B-Chemical
+support	O
+the	O
+idea	O
+that	O
+toxins	O
+other	O
+than	O
+nicotine	B-Chemical
+are	O
+the	O
+most	O
+important	O
+causes	O
+of	O
+acute	O
+cardiovascular	O
+events	O
+.	O
+
+Finally	O
+,	O
+the	O
+dose	O
+response	O
+for	O
+cardiovascular	O
+events	O
+of	O
+nicotine	B-Chemical
+appears	O
+to	O
+be	O
+flat	O
+,	O
+suggesting	O
+that	O
+if	O
+nicotine	B-Chemical
+is	O
+involved	O
+,	O
+adverse	O
+effects	O
+might	O
+be	O
+seen	O
+with	O
+relatively	O
+low	O
+-	O
+level	O
+cigarette	O
+exposures	O
+.	O
+
+Iatrogenically	O
+induced	O
+intractable	O
+atrioventricular	B-Disease
+reentrant	I-Disease
+tachycardia	I-Disease
+after	O
+verapamil	B-Chemical
+and	O
+catheter	O
+ablation	O
+in	O
+a	O
+patient	O
+with	O
+Wolff	B-Disease
+-	I-Disease
+Parkinson	I-Disease
+-	I-Disease
+White	I-Disease
+syndrome	I-Disease
+and	O
+idiopathic	B-Disease
+dilated	I-Disease
+cardiomyopathy	I-Disease
+.	O
+
+In	O
+a	O
+patient	O
+with	O
+WPW	B-Disease
+syndrome	I-Disease
+and	O
+idiopathic	B-Disease
+dilated	I-Disease
+cardiomyopathy	I-Disease
+,	O
+intractable	O
+atrioventricular	B-Disease
+reentrant	I-Disease
+tachycardia	I-Disease
+(	O
+AVRT	B-Disease
+)	O
+was	O
+iatrogenically	O
+induced	O
+.	O
+
+QRS	O
+without	O
+preexcitation	O
+,	O
+caused	O
+by	O
+junctional	O
+escape	O
+beats	O
+after	O
+verapamil	B-Chemical
+or	O
+unidirectional	O
+antegrade	O
+block	O
+of	O
+accessory	O
+pathway	O
+after	O
+catheter	O
+ablation	O
+,	O
+established	O
+frequent	O
+AVRT	B-Disease
+attack	O
+.	O
+
+Epidemic	O
+of	O
+liver	B-Disease
+disease	I-Disease
+caused	O
+by	O
+hydrochlorofluorocarbons	B-Chemical
+used	O
+as	O
+ozone	B-Chemical
+-	O
+sparing	O
+substitutes	O
+of	O
+chlorofluorocarbons	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+Hydrochlorofluorocarbons	B-Chemical
+(	O
+HCFCs	B-Chemical
+)	O
+are	O
+used	O
+increasingly	O
+in	O
+industry	O
+as	O
+substitutes	O
+for	O
+ozone	B-Chemical
+-	O
+depleting	O
+chlorofluorocarbons	B-Chemical
+(	O
+CFCs	B-Chemical
+)	O
+.	O
+
+Limited	O
+studies	O
+in	O
+animals	O
+indicate	O
+potential	O
+hepatotoxicity	B-Disease
+of	O
+some	O
+of	O
+these	O
+compounds	O
+.	O
+
+We	O
+investigated	O
+an	O
+epidemic	O
+of	O
+liver	B-Disease
+disease	I-Disease
+in	O
+nine	O
+industrial	O
+workers	O
+who	O
+had	O
+had	O
+repeated	O
+accidental	O
+exposure	O
+to	O
+a	O
+mixture	O
+of	O
+1	B-Chemical
+,	I-Chemical
+1	I-Chemical
+-	I-Chemical
+dichloro	I-Chemical
+-	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+trifluoroethane	I-Chemical
+(	O
+HCFC	B-Chemical
+123	I-Chemical
+)	O
+and	O
+1	B-Chemical
+-	I-Chemical
+chloro	I-Chemical
+-	I-Chemical
+1	I-Chemical
+,	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+tetrafluoroethane	I-Chemical
+(	O
+HCFC	B-Chemical
+124	I-Chemical
+)	O
+.	O
+
+All	O
+nine	O
+exposed	O
+workers	O
+were	O
+affected	O
+to	O
+various	O
+degrees	O
+.	O
+
+Both	O
+compounds	O
+are	O
+metabolised	O
+in	O
+the	O
+same	O
+way	O
+as	O
+1	B-Chemical
+-	I-Chemical
+bromo	I-Chemical
+-	I-Chemical
+1	I-Chemical
+-	I-Chemical
+chloro	I-Chemical
+-	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+,	I-Chemical
+2	I-Chemical
+-	I-Chemical
+trifluoroethane	I-Chemical
+(	O
+halothane	B-Chemical
+)	O
+to	O
+form	O
+reactive	O
+trifluoroacetyl	B-Chemical
+halide	O
+intermediates	O
+,	O
+which	O
+have	O
+been	O
+implicated	O
+in	O
+the	O
+hepatotoxicity	B-Disease
+of	O
+halothane	B-Chemical
+.	O
+
+We	O
+aimed	O
+to	O
+test	O
+whether	O
+HCFCs	B-Chemical
+123	I-Chemical
+and	I-Chemical
+124	I-Chemical
+can	O
+result	O
+in	O
+serious	O
+liver	B-Disease
+disease	I-Disease
+.	O
+
+METHODS	O
+:	O
+For	O
+one	O
+severely	O
+affected	O
+worker	O
+liver	O
+biopsy	O
+and	O
+immunohistochemical	O
+stainings	O
+for	O
+the	O
+presence	O
+of	O
+trifluoroacetyl	B-Chemical
+protein	O
+adducts	O
+were	O
+done	O
+.	O
+
+The	O
+serum	O
+of	O
+six	O
+affected	O
+workers	O
+and	O
+five	O
+controls	O
+was	O
+tested	O
+for	O
+autoantibodies	O
+that	O
+react	O
+with	O
+human	O
+liver	O
+cytochrome	O
+-	O
+P450	O
+2E1	O
+(	O
+P450	O
+2E1	O
+)	O
+and	O
+P58	O
+protein	O
+disulphide	O
+isomerase	O
+isoform	O
+(	O
+P58	O
+)	O
+.	O
+
+FINDINGS	O
+:	O
+The	O
+liver	O
+biopsy	O
+sample	O
+showed	O
+hepatocellular	O
+necrosis	B-Disease
+which	O
+was	O
+prominent	O
+in	O
+perivenular	O
+zone	O
+three	O
+and	O
+extended	O
+focally	O
+from	O
+portal	O
+tracts	O
+to	O
+portal	O
+tracts	O
+and	O
+centrilobular	O
+areas	O
+(	O
+bridging	O
+necrosis	B-Disease
+)	O
+.	O
+
+Trifluoroacetyl	B-Chemical
+-	O
+adducted	O
+proteins	O
+were	O
+detected	O
+in	O
+surviving	O
+hepatocytes	O
+.	O
+
+Autoantibodies	O
+against	O
+P450	O
+2E1	O
+or	O
+P58	O
+,	O
+previously	O
+associated	O
+with	O
+halothane	B-Disease
+hepatitis	I-Disease
+,	O
+were	O
+detected	O
+in	O
+the	O
+serum	O
+of	O
+five	O
+affected	O
+workers	O
+.	O
+
+INTERPRETATION	O
+:	O
+Repeated	O
+exposure	O
+of	O
+human	O
+beings	O
+to	O
+HCFCs	B-Chemical
+123	I-Chemical
+and	I-Chemical
+124	I-Chemical
+can	O
+result	O
+in	O
+serious	O
+liver	B-Disease
+injury	I-Disease
+in	O
+a	O
+large	O
+proportion	O
+of	O
+the	O
+exposed	O
+population	O
+.	O
+
+Although	O
+the	O
+exact	O
+mechanism	O
+of	O
+hepatotoxicity	B-Disease
+of	O
+these	O
+agents	O
+is	O
+not	O
+known	O
+,	O
+the	O
+results	O
+suggest	O
+that	O
+trifluoroacetyl	B-Chemical
+-	O
+altered	O
+liver	O
+proteins	O
+are	O
+involved	O
+.	O
+
+In	O
+view	O
+of	O
+the	O
+potentially	O
+widespread	O
+use	O
+of	O
+these	O
+compounds	O
+,	O
+there	O
+is	O
+an	O
+urgent	O
+need	O
+to	O
+develop	O
+safer	O
+alternatives	O
+.	O
+
+Bile	B-Disease
+duct	I-Disease
+hamartoma	I-Disease
+occurring	O
+in	O
+association	O
+with	O
+long	O
+-	O
+term	O
+treatment	O
+with	O
+danazol	B-Chemical
+.	O
+
+We	O
+report	O
+a	O
+case	O
+of	O
+bile	B-Disease
+duct	I-Disease
+hamartoma	I-Disease
+which	O
+developed	O
+in	O
+a	O
+patient	O
+who	O
+had	O
+been	O
+on	O
+long	O
+-	O
+term	O
+danazol	B-Chemical
+treatment	O
+.	O
+
+Such	O
+patients	O
+should	O
+be	O
+under	O
+close	O
+follow	O
+-	O
+up	O
+,	O
+preferably	O
+with	O
+periodic	O
+ultrasound	O
+examination	O
+of	O
+the	O
+liver	O
+.	O
+
+If	O
+the	O
+patient	O
+develops	O
+a	O
+liver	B-Disease
+mass	I-Disease
+,	O
+because	O
+of	O
+non	O
+-	O
+specific	O
+clinical	O
+features	O
+and	O
+imaging	O
+appearances	O
+,	O
+biopsy	O
+may	O
+be	O
+the	O
+only	O
+way	O
+to	O
+achieve	O
+a	O
+definitive	O
+diagnosis	O
+.	O
+
+Endocrine	O
+screening	O
+in	O
+1	O
+,	O
+022	O
+men	O
+with	O
+erectile	B-Disease
+dysfunction	I-Disease
+:	O
+clinical	O
+significance	O
+and	O
+cost	O
+-	O
+effective	O
+strategy	O
+.	O
+
+PURPOSE	O
+:	O
+We	O
+reviewed	O
+the	O
+results	O
+of	O
+serum	O
+testosterone	B-Chemical
+and	O
+prolactin	O
+determination	O
+in	O
+1	O
+,	O
+022	O
+patients	O
+referred	O
+because	O
+of	O
+erectile	B-Disease
+dysfunction	I-Disease
+and	O
+compared	O
+the	O
+data	O
+with	O
+history	O
+,	O
+results	O
+of	O
+physical	O
+examination	O
+,	O
+other	O
+etiological	O
+investigations	O
+and	O
+effects	O
+of	O
+endocrine	O
+therapy	O
+to	O
+refine	O
+the	O
+rules	O
+of	O
+cost	O
+-	O
+effective	O
+endocrine	O
+screening	O
+and	O
+to	O
+pinpoint	O
+actual	O
+responsibility	O
+for	O
+hormonal	O
+abnormalities	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+:	O
+Testosterone	B-Chemical
+and	O
+prolactin	O
+were	O
+determined	O
+by	O
+radioimmunoassay	O
+.	O
+
+Every	O
+patient	O
+was	O
+screened	O
+for	O
+testosterone	B-Chemical
+and	O
+451	O
+were	O
+screened	O
+for	O
+prolactin	O
+on	O
+the	O
+basis	O
+of	O
+low	B-Disease
+sexual	I-Disease
+desire	I-Disease
+,	O
+gynecomastia	B-Disease
+or	O
+testosterone	B-Chemical
+less	O
+than	O
+4	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+
+Determination	O
+was	O
+repeated	O
+in	O
+case	O
+of	O
+abnormal	O
+first	O
+results	O
+.	O
+
+Prolactin	O
+results	O
+were	O
+compared	O
+with	O
+those	O
+of	O
+a	O
+previous	O
+personal	O
+cohort	O
+of	O
+1	O
+,	O
+340	O
+patients	O
+with	O
+erectile	B-Disease
+dysfunction	I-Disease
+and	O
+systematic	O
+prolactin	O
+determination	O
+.	O
+
+Main	O
+clinical	O
+criteria	O
+tested	O
+regarding	O
+efficiency	O
+in	O
+hormone	O
+determination	O
+were	O
+low	B-Disease
+sexual	I-Disease
+desire	I-Disease
+,	O
+small	O
+testes	O
+and	O
+gynecomastia	B-Disease
+.	O
+
+Endocrine	O
+therapy	O
+consisted	O
+of	O
+testosterone	B-Chemical
+heptylate	I-Chemical
+or	O
+human	O
+chorionic	O
+gonadotropin	O
+for	O
+hypogonadism	B-Disease
+and	O
+bromocriptine	B-Chemical
+for	O
+hyperprolactinemia	B-Disease
+.	O
+
+RESULTS	O
+:	O
+Testosterone	B-Chemical
+was	O
+less	O
+than	O
+3	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+in	O
+107	O
+patients	O
+but	O
+normal	O
+in	O
+40	O
+%	O
+at	O
+repeat	O
+determination	O
+.	O
+
+The	O
+prevalence	O
+of	O
+repeatedly	O
+low	O
+testosterone	B-Chemical
+increased	O
+with	O
+age	O
+(	O
+4	O
+%	O
+before	O
+age	O
+50	O
+years	O
+and	O
+9	O
+%	O
+50	O
+years	O
+or	O
+older	O
+)	O
+.	O
+
+Two	O
+pituitary	B-Disease
+tumors	I-Disease
+were	O
+discovered	O
+after	O
+testosterone	B-Chemical
+determination	O
+.	O
+
+Most	O
+of	O
+the	O
+other	O
+low	O
+testosterone	B-Chemical
+levels	O
+seemed	O
+to	O
+result	O
+from	O
+nonorganic	O
+hypothalamic	B-Disease
+dysfunction	I-Disease
+because	O
+of	O
+normal	O
+serum	O
+luteinizing	O
+hormone	O
+and	O
+prolactin	O
+and	O
+to	O
+have	O
+only	O
+a	O
+small	O
+role	O
+in	O
+erectile	B-Disease
+dysfunction	I-Disease
+(	O
+definite	O
+improvement	O
+in	O
+only	O
+16	O
+of	O
+44	O
+[	O
+36	O
+%	O
+]	O
+after	O
+androgen	O
+therapy	O
+,	O
+normal	O
+morning	O
+or	O
+nocturnal	O
+erections	O
+in	O
+30	O
+%	O
+and	O
+definite	O
+vasculogenic	O
+contributions	O
+in	O
+42	O
+%	O
+)	O
+.	O
+
+Determining	O
+testosterone	B-Chemical
+only	O
+in	O
+cases	O
+of	O
+low	B-Disease
+sexual	I-Disease
+desire	I-Disease
+or	O
+abnormal	O
+physical	O
+examination	O
+would	O
+have	O
+missed	O
+40	O
+%	O
+of	O
+the	O
+cases	O
+with	O
+low	O
+testosterone	B-Chemical
+,	O
+including	O
+37	O
+%	O
+of	O
+those	O
+subsequently	O
+improved	O
+by	O
+androgen	O
+therapy	O
+.	O
+
+Prolactin	O
+exceeded	O
+20	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+in	O
+5	O
+men	O
+and	O
+was	O
+normal	O
+in	O
+2	O
+at	O
+repeat	O
+determination	O
+.	O
+
+Only	O
+1	O
+prolactinoma	B-Disease
+was	O
+discovered	O
+.	O
+
+These	O
+data	O
+are	O
+lower	O
+than	O
+those	O
+we	O
+found	O
+during	O
+the	O
+last	O
+2	O
+decades	O
+(	O
+overall	O
+prolactin	O
+greater	O
+than	O
+20	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+in	O
+1	O
+.	O
+86	O
+%	O
+of	O
+1	O
+,	O
+821	O
+patients	O
+,	O
+prolactinomas	B-Disease
+in	O
+7	O
+,	O
+0	O
+.	O
+38	O
+%	O
+)	O
+.	O
+
+Bromocriptine	B-Chemical
+was	O
+definitely	O
+effective	O
+in	O
+cases	O
+with	O
+prolactin	O
+greater	O
+than	O
+35	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+
+(	O
+8	O
+of	O
+12	O
+compared	O
+to	O
+only	O
+9	O
+of	O
+22	O
+cases	O
+with	O
+prolactin	O
+between	O
+20	O
+and	O
+35	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+)	O
+.	O
+
+Testosterone	B-Chemical
+was	O
+low	O
+in	O
+less	O
+than	O
+50	O
+%	O
+of	O
+cases	O
+with	O
+prolactin	O
+greater	O
+than	O
+35	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Low	O
+prevalences	O
+and	O
+effects	O
+of	O
+low	O
+testosterone	B-Chemical
+and	O
+high	O
+prolactin	O
+in	O
+erectile	B-Disease
+dysfunction	I-Disease
+cannot	O
+justify	O
+their	O
+routine	O
+determination	O
+.	O
+
+However	O
+,	O
+cost	O
+-	O
+effective	O
+screening	O
+strategies	O
+recommended	O
+so	O
+far	O
+missed	O
+40	O
+to	O
+50	O
+%	O
+of	O
+cases	O
+improved	O
+with	O
+endocrine	O
+therapy	O
+and	O
+the	O
+pituitary	B-Disease
+tumors	I-Disease
+.	O
+
+We	O
+now	O
+advocate	O
+that	O
+before	O
+age	O
+50	O
+years	O
+testosterone	B-Chemical
+be	O
+determined	O
+only	O
+in	O
+cases	O
+of	O
+low	B-Disease
+sexual	I-Disease
+desire	I-Disease
+and	O
+abnormal	O
+physical	O
+examination	O
+but	O
+that	O
+it	O
+be	O
+measured	O
+in	O
+all	O
+men	O
+older	O
+than	O
+50	O
+years	O
+.	O
+
+Prolactin	O
+should	O
+be	O
+determined	O
+only	O
+in	O
+cases	O
+of	O
+low	B-Disease
+sexual	I-Disease
+desire	I-Disease
+,	O
+gynecomastia	B-Disease
+and	O
+/	O
+or	O
+testosterone	B-Chemical
+less	O
+than	O
+4	O
+ng	O
+.	O
+/	O
+ml	O
+.	O
+
+Extrapyramidal	O
+side	O
+effects	O
+with	O
+risperidone	B-Chemical
+and	O
+haloperidol	B-Chemical
+at	O
+comparable	O
+D2	O
+receptor	O
+occupancy	O
+levels	O
+.	O
+
+Risperidone	B-Chemical
+is	O
+an	O
+antipsychotic	O
+drug	O
+with	O
+high	O
+affinity	O
+at	O
+dopamine	B-Chemical
+D2	O
+and	O
+serotonin	B-Chemical
+5	I-Chemical
+-	I-Chemical
+HT2	I-Chemical
+receptors	O
+.	O
+
+Previous	O
+clinical	O
+studies	O
+have	O
+proposed	O
+that	O
+risperidone	B-Chemical
+'	O
+s	O
+pharmacologic	O
+profile	O
+may	O
+produce	O
+improved	O
+efficacy	O
+for	O
+negative	O
+psychotic	B-Disease
+symptoms	I-Disease
+and	O
+decreased	O
+propensity	O
+for	O
+extrapyramidal	O
+side	O
+effects	O
+;	O
+features	O
+shared	O
+by	O
+so	O
+-	O
+called	O
+'	O
+atypical	O
+'	O
+neuroleptics	O
+.	O
+
+To	O
+determine	O
+if	O
+routine	O
+risperidone	B-Chemical
+treatment	O
+is	O
+associated	O
+with	O
+a	O
+unique	O
+degree	O
+of	O
+D2	O
+receptor	O
+occupancy	O
+and	O
+pattern	O
+of	O
+clinical	O
+effects	O
+,	O
+we	O
+used	O
+[	O
+123I	O
+]	O
+IBZM	O
+SPECT	O
+to	O
+determine	O
+D2	O
+occupancy	O
+in	O
+subjects	O
+treated	O
+with	O
+routine	O
+clinical	O
+doses	O
+of	O
+risperidone	B-Chemical
+(	O
+n	O
+=	O
+12	O
+)	O
+or	O
+haloperidol	B-Chemical
+(	O
+n	O
+=	O
+7	O
+)	O
+.	O
+
+Both	O
+risperidone	B-Chemical
+and	O
+haloperidol	B-Chemical
+produced	O
+D2	O
+occupancy	O
+levels	O
+between	O
+approximately	O
+60	O
+and	O
+90	O
+%	O
+at	O
+standard	O
+clinical	O
+doses	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
+difference	O
+between	O
+occupancy	O
+levels	O
+obtained	O
+with	O
+haloperidol	B-Chemical
+or	O
+risperidone	B-Chemical
+.	O
+
+Drug	B-Disease
+-	I-Disease
+induced	I-Disease
+parkinsonism	I-Disease
+was	O
+observed	O
+in	O
+subjects	O
+treated	O
+with	O
+risperidone	B-Chemical
+(	O
+42	O
+%	O
+)	O
+and	O
+haloperidol	B-Chemical
+(	O
+29	O
+%	O
+)	O
+and	O
+was	O
+observed	O
+at	O
+occupancy	O
+levels	O
+above	O
+60	O
+%	O
+.	O
+
+Based	O
+on	O
+these	O
+observations	O
+,	O
+it	O
+is	O
+concluded	O
+that	O
+5	O
+-	O
+HT2	O
+blockade	O
+obtained	O
+with	O
+risperidone	B-Chemical
+at	O
+D2	O
+occupancy	O
+rates	O
+of	O
+60	O
+%	O
+and	O
+above	O
+does	O
+not	O
+appear	O
+to	O
+protect	O
+against	O
+the	O
+risk	O
+for	O
+extrapyramidal	O
+side	O
+effects	O
+.	O
+
+Treatment	O
+of	O
+previously	O
+treated	O
+metastatic	O
+breast	B-Disease
+cancer	I-Disease
+by	O
+mitoxantrone	B-Chemical
+and	O
+48	O
+-	O
+hour	O
+continuous	O
+infusion	O
+of	O
+high	O
+-	O
+dose	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+and	O
+leucovorin	B-Chemical
+(	O
+MFL	B-Chemical
+)	O
+:	O
+low	O
+palliative	O
+benefit	O
+and	O
+high	O
+treatment	O
+-	O
+related	O
+toxicity	B-Disease
+.	O
+
+For	O
+previously	O
+treated	O
+advanced	O
+breast	B-Disease
+cancer	I-Disease
+,	O
+there	O
+is	O
+no	O
+standard	O
+second	O
+-	O
+line	O
+therapy	O
+.	O
+
+Combination	O
+chemotherapy	O
+with	O
+mitoxantrone	B-Chemical
+,	O
+high	O
+-	O
+dose	O
+5	B-Chemical
+-	I-Chemical
+fluorouracil	I-Chemical
+(	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+)	O
+and	O
+leucovorin	B-Chemical
+(	O
+MFL	B-Chemical
+regimen	I-Chemical
+)	O
+had	O
+been	O
+reported	O
+as	O
+an	O
+effective	O
+and	O
+well	O
+tolerated	O
+regimen	O
+.	O
+
+From	O
+October	O
+1993	O
+to	O
+November	O
+1995	O
+,	O
+we	O
+treated	O
+13	O
+patients	O
+with	O
+previously	O
+chemotherapy	O
+-	O
+treated	O
+metastatic	O
+breast	B-Disease
+cancer	I-Disease
+by	O
+mitoxantrone	B-Chemical
+,	O
+12	O
+mg	O
+/	O
+m2	O
+,	O
+on	O
+day	O
+1	O
+and	O
+continuous	O
+infusion	O
+of	O
+5	B-Chemical
+-	I-Chemical
+FU	I-Chemical
+,	O
+3000	O
+mg	O
+/	O
+m2	O
+,	O
+together	O
+with	O
+leucovorin	B-Chemical
+,	O
+300	O
+mg	O
+/	O
+m2	O
+,	O
+for	O
+48	O
+h	O
+from	O
+day	O
+1	O
+to	O
+2	O
+.	O
+
+Each	O
+course	O
+of	O
+chemotherapy	O
+was	O
+given	O
+every	O
+4	O
+weeks	O
+.	O
+
+Most	O
+of	O
+these	O
+patients	O
+had	O
+more	O
+than	O
+two	O
+metastatic	O
+sites	O
+,	O
+with	O
+lung	O
+metastasis	O
+predominant	O
+.	O
+
+Seven	O
+patients	O
+had	O
+been	O
+treated	O
+with	O
+anthracycline	B-Chemical
+.	O
+
+Seven	O
+patients	O
+had	O
+previously	O
+received	O
+radiotherapy	O
+and	O
+seven	O
+had	O
+received	O
+hormone	O
+therapy	O
+.	O
+
+Median	O
+number	O
+of	O
+courses	O
+of	O
+MFL	B-Chemical
+regimen	I-Chemical
+given	O
+was	O
+six	O
+and	O
+the	O
+median	O
+cumulative	O
+dose	O
+of	O
+mitoxantrone	B-Chemical
+was	O
+68	O
+.	O
+35	O
+mg	O
+/	O
+m2	O
+.	O
+
+One	O
+patient	O
+had	O
+complete	O
+response	O
+,	O
+seven	O
+had	O
+stable	O
+disease	O
+,	O
+none	O
+had	O
+partial	O
+response	O
+and	O
+five	O
+had	O
+progressive	O
+disease	O
+.	O
+
+The	O
+overall	O
+objective	O
+response	O
+rate	O
+was	O
+7	O
+.	O
+6	O
+%	O
+.	O
+
+The	O
+median	O
+follow	O
+-	O
+up	O
+period	O
+was	O
+14	O
+months	O
+.	O
+
+Median	O
+survival	O
+was	O
+16	O
+months	O
+.	O
+
+Median	O
+progression	O
+-	O
+free	O
+survival	O
+was	O
+5	O
+months	O
+.	O
+
+A	O
+complete	O
+responder	O
+had	O
+relapse	O
+-	O
+free	O
+survival	O
+up	O
+to	O
+17	O
+months	O
+.	O
+
+Major	O
+toxicities	B-Disease
+were	O
+cardiotoxicity	B-Disease
+and	O
+leukopenia	B-Disease
+.	O
+
+Eight	O
+patients	O
+were	O
+dead	O
+in	O
+the	O
+last	O
+follow	O
+-	O
+up	O
+;	O
+two	O
+of	O
+them	O
+died	O
+of	O
+treatment	O
+-	O
+related	O
+toxicity	B-Disease
+.	O
+
+The	O
+MFL	B-Chemical
+regimen	I-Chemical
+achieves	O
+little	O
+palliative	O
+benefit	O
+and	O
+induces	O
+severe	O
+toxicity	B-Disease
+at	O
+a	O
+fairly	O
+high	O
+rate	O
+.	O
+
+Administration	O
+of	O
+this	O
+regimen	O
+to	O
+breast	B-Disease
+cancer	I-Disease
+patients	O
+who	O
+have	O
+been	O
+treated	O
+by	O
+chemotherapy	O
+and	O
+those	O
+with	O
+impaired	B-Disease
+heart	I-Disease
+function	I-Disease
+requires	O
+careful	O
+attention	O
+.	O
+
+Ticlopidine	B-Chemical
+-	O
+induced	O
+aplastic	B-Disease
+anemia	I-Disease
+:	O
+report	O
+of	O
+three	O
+Chinese	O
+patients	O
+and	O
+review	O
+of	O
+the	O
+literature	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+three	O
+Chinese	O
+patients	O
+with	O
+ticlopidine	B-Chemical
+-	O
+induced	O
+aplastic	B-Disease
+anemia	I-Disease
+were	O
+reported	O
+and	O
+another	O
+13	O
+patients	O
+in	O
+the	O
+English	O
+literature	O
+were	O
+reviewed	O
+.	O
+
+We	O
+attempted	O
+to	O
+find	O
+underlying	O
+similarities	O
+,	O
+evaluate	O
+the	O
+risk	O
+factors	O
+,	O
+and	O
+identify	O
+appropriate	O
+treatment	O
+for	O
+this	O
+complication	O
+.	O
+
+All	O
+but	O
+one	O
+of	O
+the	O
+patients	O
+were	O
+over	O
+60	O
+years	O
+old	O
+,	O
+and	O
+the	O
+6	O
+who	O
+died	O
+were	O
+all	O
+older	O
+than	O
+65	O
+.	O
+
+Therefore	O
+,	O
+old	O
+age	O
+may	O
+be	O
+a	O
+risk	O
+factor	O
+for	O
+developing	O
+this	O
+complication	O
+.	O
+
+Agranulocytosis	B-Disease
+occurred	O
+3	O
+-	O
+20	O
+weeks	O
+after	O
+initiation	O
+of	O
+ticlopidine	B-Chemical
+,	O
+so	O
+frequent	O
+examination	O
+of	O
+white	O
+cell	O
+count	O
+during	O
+treatment	O
+is	O
+recommended	O
+.	O
+
+There	O
+seemed	O
+to	O
+be	O
+no	O
+direct	O
+correlation	O
+between	O
+the	O
+dose	O
+or	O
+duration	O
+used	O
+and	O
+the	O
+severity	O
+of	O
+bone	B-Disease
+marrow	I-Disease
+suppression	I-Disease
+.	O
+
+Treatment	O
+for	O
+ticlopidine	B-Chemical
+-	O
+induced	O
+aplastic	B-Disease
+anemia	I-Disease
+with	O
+colony	O
+-	O
+stimulating	O
+factors	O
+seemed	O
+to	O
+have	O
+little	O
+effect	O
+.	O
+
+The	O
+fact	O
+that	O
+5	O
+of	O
+the	O
+6	O
+patients	O
+who	O
+received	O
+concurrent	O
+calcium	B-Chemical
+channel	O
+blockers	O
+died	O
+,	O
+should	O
+alert	O
+clinicians	O
+to	O
+be	O
+more	O
+cautious	O
+when	O
+using	O
+these	O
+two	O
+drugs	O
+simultaneously	O
+.	O
+
+Upregulation	O
+of	O
+the	O
+expression	O
+of	O
+vasopressin	B-Chemical
+gene	O
+in	O
+the	O
+paraventricular	O
+and	O
+supraoptic	O
+nuclei	O
+of	O
+the	O
+lithium	B-Chemical
+-	O
+induced	O
+diabetes	B-Disease
+insipidus	I-Disease
+rat	O
+.	O
+
+The	O
+expression	O
+of	O
+arginine	B-Chemical
+vasopressin	I-Chemical
+(	O
+AVP	B-Chemical
+)	O
+gene	O
+in	O
+the	O
+paraventricular	O
+(	O
+PVN	O
+)	O
+and	O
+supraoptic	O
+nuclei	O
+(	O
+SON	O
+)	O
+was	O
+investigated	O
+in	O
+rats	O
+with	O
+lithium	B-Chemical
+(	O
+Li	B-Chemical
+)	O
+-	O
+induced	O
+polyuria	B-Disease
+,	O
+using	O
+in	O
+situ	O
+hybridization	O
+histochemistry	O
+and	O
+radioimmunoassay	O
+.	O
+
+The	O
+male	O
+Wistar	O
+rats	O
+consuming	O
+a	O
+diet	O
+that	O
+contained	O
+LiCl	B-Chemical
+(	O
+60	O
+mmol	O
+/	O
+kg	O
+)	O
+for	O
+4	O
+weeks	O
+developed	O
+marked	O
+polyuria	B-Disease
+.	O
+
+The	O
+Li	B-Chemical
+-	O
+treated	O
+rats	O
+produced	O
+a	O
+large	O
+volume	O
+of	O
+hypotonic	O
+urine	O
+with	O
+low	O
+ionic	O
+concentrations	O
+.	O
+
+Plasma	O
+sodium	B-Chemical
+concentrations	O
+were	O
+found	O
+to	O
+be	O
+slightly	O
+increased	O
+in	O
+the	O
+Li	B-Chemical
+-	O
+treated	O
+rats	O
+compared	O
+with	O
+those	O
+in	O
+controls	O
+.	O
+
+Plasma	O
+concentration	O
+of	O
+AVP	B-Chemical
+and	O
+transcripts	O
+of	O
+AVP	B-Chemical
+gene	O
+in	O
+the	O
+PVN	O
+and	O
+SON	O
+were	O
+significantly	O
+increased	O
+in	O
+the	O
+Li	B-Chemical
+-	O
+treated	O
+rats	O
+compared	O
+with	O
+controls	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+dehydration	B-Disease
+and	O
+/	O
+or	O
+the	O
+activation	O
+of	O
+visceral	O
+afferent	O
+inputs	O
+may	O
+contribute	O
+to	O
+the	O
+elevation	O
+of	O
+plasma	O
+AVP	B-Chemical
+and	O
+the	O
+upregulation	O
+of	O
+AVP	B-Chemical
+gene	O
+expression	O
+in	O
+the	O
+PVN	O
+and	O
+the	O
+SON	O
+of	O
+the	O
+Li	B-Chemical
+-	O
+induced	O
+diabetes	B-Disease
+insipidus	I-Disease
+rat	O
+.	O
+
+Antinociceptive	O
+and	O
+antiamnesic	O
+properties	O
+of	O
+the	O
+presynaptic	O
+cholinergic	O
+amplifier	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+.	O
+
+The	O
+antinociceptive	O
+effect	O
+of	O
+3	B-Chemical
+alpha	I-Chemical
+-	I-Chemical
+tropyl	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+p	I-Chemical
+-	I-Chemical
+bromophenyl	I-Chemical
+)	I-Chemical
+propionate	I-Chemical
+[	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+]	O
+(	O
+10	O
+-	O
+40	O
+mg	O
+kg	O
+-	O
+1	O
+s	O
+.	O
+c	O
+.	O
+;	O
+30	O
+-	O
+60	O
+mg	O
+kg	O
+-	O
+1	O
+p	O
+.	O
+o	O
+.	O
+;	O
+10	O
+-	O
+30	O
+mg	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+v	O
+.	O
+;	O
+10	O
+-	O
+30	O
+micrograms	O
+/	O
+mouse	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+)	O
+was	O
+examined	O
+in	O
+mice	O
+,	O
+rats	O
+and	O
+guinea	O
+pigs	O
+by	O
+use	O
+of	O
+the	O
+hot	O
+-	O
+plate	O
+,	O
+abdominal	O
+-	O
+constriction	O
+,	O
+tail	O
+-	O
+flick	O
+and	O
+paw	O
+-	O
+pressure	O
+tests	O
+.	O
+
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+antinociception	O
+peaked	O
+15	O
+min	O
+after	O
+injection	O
+and	O
+then	O
+slowly	O
+diminished	O
+.	O
+
+The	O
+antinociception	O
+produced	O
+by	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+was	O
+prevented	O
+by	O
+the	O
+unselective	O
+muscarinic	O
+antagonist	O
+atropine	B-Chemical
+,	O
+the	O
+M1	O
+-	O
+selective	O
+antagonists	O
+pirenzepine	B-Chemical
+and	O
+dicyclomine	B-Chemical
+and	O
+the	O
+acetylcholine	B-Chemical
+depletor	O
+hemicholinium	B-Chemical
+-	I-Chemical
+3	I-Chemical
+,	O
+but	O
+not	O
+by	O
+the	O
+opioid	O
+antagonist	O
+naloxone	B-Chemical
+,	O
+the	O
+gamma	B-Chemical
+-	I-Chemical
+aminobutyric	I-Chemical
+acidB	I-Chemical
+antagonist	O
+3	B-Chemical
+-	I-Chemical
+aminopropyl	I-Chemical
+-	I-Chemical
+diethoxy	I-Chemical
+-	I-Chemical
+methyl	I-Chemical
+-	I-Chemical
+phosphinic	I-Chemical
+acid	I-Chemical
+,	O
+the	O
+H3	O
+agonist	O
+R	B-Chemical
+-	I-Chemical
+(	I-Chemical
+alpha	I-Chemical
+)	I-Chemical
+-	I-Chemical
+methylhistamine	I-Chemical
+,	O
+the	O
+D2	O
+antagonist	O
+quinpirole	B-Chemical
+,	O
+the	O
+5	B-Chemical
+-	I-Chemical
+hydroxytryptamine4	I-Chemical
+antagonist	O
+2	B-Chemical
+-	I-Chemical
+methoxy	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+amino	I-Chemical
+-	I-Chemical
+5	I-Chemical
+-	I-Chemical
+chlorobenzoic	I-Chemical
+acid	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+diethylamino	I-Chemical
+)	I-Chemical
+ethyl	I-Chemical
+ester	I-Chemical
+hydrochloride	O
+,	O
+the	O
+5	B-Chemical
+-	I-Chemical
+hydroxytryptamin1A	I-Chemical
+antagonist	O
+1	B-Chemical
+-	I-Chemical
+(	I-Chemical
+2	I-Chemical
+-	I-Chemical
+methoxyphenyl	I-Chemical
+)	I-Chemical
+-	I-Chemical
+4	I-Chemical
+-	I-Chemical
+[	I-Chemical
+4	I-Chemical
+-	I-Chemical
+(	I-Chemical
+2	I-Chemical
+-	I-Chemical
+phthalimido	I-Chemical
+)	I-Chemical
+butyl	I-Chemical
+]	I-Chemical
+piperazine	I-Chemical
+hydrobromide	O
+and	O
+the	O
+polyamines	O
+depletor	O
+reserpine	B-Chemical
+.	O
+
+Based	O
+on	O
+these	O
+data	O
+,	O
+it	O
+can	O
+be	O
+postulated	O
+that	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+exerted	O
+an	O
+antinociceptive	O
+effect	O
+mediated	O
+by	O
+a	O
+central	O
+potentiation	O
+of	O
+cholinergic	O
+transmission	O
+.	O
+
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+(	O
+10	O
+-	O
+40	O
+mg	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+p	O
+.	O
+)	O
+was	O
+able	O
+to	O
+prevent	O
+amnesia	B-Disease
+induced	O
+by	O
+scopolamine	B-Chemical
+(	O
+1	O
+mg	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+p	O
+.	O
+)	O
+and	O
+dicyclomine	B-Chemical
+(	O
+2	O
+mg	O
+kg	O
+-	O
+1	O
+i	O
+.	O
+p	O
+.	O
+)	O
+in	O
+the	O
+mouse	O
+passive	O
+-	O
+avoidance	O
+test	O
+.	O
+
+Affinity	O
+profiles	O
+of	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+for	O
+muscarinic	O
+receptor	O
+subtypes	O
+,	O
+determined	O
+by	O
+functional	O
+studies	O
+(	O
+rabbit	O
+vas	O
+deferens	O
+for	O
+M1	O
+,	O
+guinea	O
+pig	O
+atrium	O
+for	O
+M2	O
+,	O
+guinea	O
+pig	O
+ileum	O
+for	O
+M3	O
+and	O
+immature	O
+guinea	O
+pig	O
+uterus	O
+for	O
+putative	O
+M4	O
+)	O
+,	O
+have	O
+shown	O
+an	O
+M4	O
+/	O
+M1	O
+selectivity	O
+ratio	O
+of	O
+10	O
+.	O
+2	O
+that	O
+might	O
+be	O
+responsible	O
+for	O
+the	O
+antinociception	O
+and	O
+the	O
+anti	O
+-	O
+amnesic	B-Disease
+effect	O
+induced	O
+by	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+through	O
+an	O
+increase	O
+in	O
+acetylcholine	B-Chemical
+extracellular	O
+levels	O
+.	O
+
+In	O
+the	O
+antinociceptive	O
+and	O
+antiamnesic	O
+dose	O
+range	O
+,	O
+(	O
++	O
+/	O
+-	O
+)	O
+-	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+did	O
+not	O
+impair	O
+mouse	O
+performance	O
+evaluated	O
+by	O
+the	O
+rota	O
+-	O
+rod	O
+test	O
+and	O
+Animex	O
+apparatus	O
+.	O
+
+The	O
+effect	O
+of	O
+different	O
+anaesthetic	O
+agents	O
+in	O
+hearing	B-Disease
+loss	I-Disease
+following	O
+spinal	O
+anaesthesia	O
+.	O
+
+The	O
+cause	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+after	O
+spinal	O
+anaesthesia	O
+is	O
+unknown	O
+.	O
+
+Up	O
+until	O
+now	O
+,	O
+the	O
+only	O
+factor	O
+studied	O
+has	O
+been	O
+the	O
+effect	O
+of	O
+the	O
+diameter	O
+of	O
+the	O
+spinal	O
+needle	O
+on	O
+post	O
+-	O
+operative	O
+sensorineural	B-Disease
+hearing	I-Disease
+loss	I-Disease
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+describe	O
+this	O
+hearing	B-Disease
+loss	I-Disease
+and	O
+to	O
+investigate	O
+other	O
+factors	O
+influencing	O
+the	O
+degree	O
+of	O
+hearing	B-Disease
+loss	I-Disease
+.	O
+
+Two	O
+groups	O
+of	O
+22	O
+similar	O
+patients	O
+were	O
+studied	O
+:	O
+one	O
+group	O
+received	O
+6	O
+mL	O
+prilocaine	B-Chemical
+2	O
+%	O
+;	O
+and	O
+the	O
+other	O
+received	O
+3	O
+mL	O
+bupivacaine	B-Chemical
+0	O
+.	O
+5	O
+%	O
+.	O
+
+Patients	O
+given	O
+prilocaine	B-Chemical
+were	O
+more	O
+likely	O
+to	O
+develop	O
+hearing	B-Disease
+loss	I-Disease
+(	O
+10	O
+out	O
+of	O
+22	O
+)	O
+than	O
+those	O
+given	O
+bupivacaine	B-Chemical
+(	O
+4	O
+out	O
+of	O
+22	O
+)	O
+(	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+average	O
+hearing	B-Disease
+loss	I-Disease
+for	O
+speech	O
+frequencies	O
+was	O
+about	O
+10	O
+dB	O
+after	O
+prilocaine	B-Chemical
+and	O
+15	O
+dB	O
+after	O
+bupivacaine	B-Chemical
+.	O
+
+None	O
+of	O
+the	O
+patients	O
+complained	O
+of	O
+subjective	O
+hearing	B-Disease
+loss	I-Disease
+.	O
+
+Long	O
+-	O
+term	O
+follow	O
+-	O
+up	O
+of	O
+the	O
+patients	O
+was	O
+not	O
+possible	O
+.	O
+
+A	O
+transient	O
+neurological	B-Disease
+deficit	I-Disease
+following	O
+intrathecal	O
+injection	O
+of	O
+1	O
+%	O
+hyperbaric	O
+bupivacaine	B-Chemical
+for	O
+unilateral	O
+spinal	O
+anaesthesia	O
+.	O
+
+We	O
+describe	O
+a	O
+case	O
+of	O
+transient	O
+neurological	B-Disease
+deficit	I-Disease
+that	O
+occurred	O
+after	O
+unilateral	O
+spinal	O
+anaesthesia	O
+with	O
+8	O
+mg	O
+of	O
+1	O
+%	O
+hyperbaric	O
+bupivacaine	B-Chemical
+slowly	O
+injected	O
+through	O
+a	O
+25	O
+-	O
+gauge	O
+pencil	O
+-	O
+point	O
+spinal	O
+needle	O
+.	O
+
+The	O
+surgery	O
+and	O
+anaesthesia	O
+were	O
+uneventful	O
+,	O
+but	O
+3	O
+days	O
+after	O
+surgery	O
+,	O
+the	O
+patient	O
+reported	O
+an	O
+area	O
+of	O
+hypoaesthesia	O
+over	O
+L3	O
+-	O
+L4	O
+dermatomes	O
+of	O
+the	O
+leg	O
+which	O
+had	O
+been	O
+operated	O
+on	O
+(	O
+loss	B-Disease
+of	I-Disease
+pinprick	I-Disease
+sensation	I-Disease
+)	O
+without	O
+reduction	O
+in	O
+muscular	O
+strength	O
+.	O
+
+Sensation	O
+in	O
+this	O
+area	O
+returned	O
+to	O
+normal	O
+over	O
+the	O
+following	O
+2	O
+weeks	O
+.	O
+
+Prospective	O
+multicentre	O
+studies	O
+with	O
+a	O
+large	O
+population	O
+and	O
+a	O
+long	O
+follow	O
+-	O
+up	O
+should	O
+be	O
+performed	O
+in	O
+order	O
+to	O
+evaluate	O
+the	O
+incidence	O
+of	O
+this	O
+unusual	O
+side	O
+effect	O
+.	O
+
+However	O
+,	O
+we	O
+suggest	O
+that	O
+a	O
+low	O
+solution	O
+concentration	O
+should	O
+be	O
+preferred	O
+for	O
+unilateral	O
+spinal	O
+anaesthesia	O
+with	O
+a	O
+hyperbaric	O
+anaesthetic	O
+solution	O
+(	O
+if	O
+pencil	O
+-	O
+point	O
+needle	O
+and	O
+slow	O
+injection	O
+rate	O
+are	O
+employed	O
+)	O
+,	O
+in	O
+order	O
+to	O
+minimize	O
+the	O
+risk	O
+of	O
+a	O
+localized	O
+high	O
+peak	O
+anaesthetic	O
+concentration	O
+,	O
+which	O
+might	O
+lead	O
+to	O
+a	O
+transient	O
+neurological	B-Disease
+deficit	I-Disease
+.	O
+
+Transient	B-Disease
+neurologic	I-Disease
+symptoms	I-Disease
+after	O
+spinal	O
+anesthesia	O
+:	O
+a	O
+lower	O
+incidence	O
+with	O
+prilocaine	B-Chemical
+and	O
+bupivacaine	B-Chemical
+than	O
+with	O
+lidocaine	B-Chemical
+.	O
+
+BACKGROUND	O
+:	O
+Recent	O
+evidence	O
+suggests	O
+that	O
+transient	B-Disease
+neurologic	I-Disease
+symptoms	I-Disease
+(	O
+TNSs	B-Disease
+)	O
+frequently	O
+follow	O
+lidocaine	B-Chemical
+spinal	O
+anesthesia	O
+but	O
+are	O
+infrequent	O
+with	O
+bupivacaine	B-Chemical
+.	O
+
+However	O
+,	O
+identification	O
+of	O
+a	O
+short	O
+-	O
+acting	O
+local	O
+anesthetic	O
+to	O
+substitute	O
+for	O
+lidocaine	B-Chemical
+for	O
+brief	O
+surgical	O
+procedures	O
+remains	O
+an	O
+important	O
+goal	O
+.	O
+
+Prilocaine	B-Chemical
+is	O
+an	O
+amide	O
+local	O
+anesthetic	O
+with	O
+a	O
+duration	O
+of	O
+action	O
+similar	O
+to	O
+that	O
+of	O
+lidocaine	B-Chemical
+.	O
+
+Accordingly	O
+,	O
+the	O
+present	O
+,	O
+prospective	O
+double	O
+-	O
+blind	O
+study	O
+compares	O
+prilocaine	B-Chemical
+with	O
+lidocaine	B-Chemical
+and	O
+bupivacaine	B-Chemical
+with	O
+respect	O
+to	O
+duration	O
+of	O
+action	O
+and	O
+relative	O
+risk	O
+of	O
+TNSs	B-Disease
+.	O
+
+METHODS	O
+:	O
+Ninety	O
+patients	O
+classified	O
+as	O
+American	O
+Society	O
+of	O
+Anesthesiologists	O
+physical	O
+status	O
+I	O
+or	O
+II	O
+who	O
+were	O
+scheduled	O
+for	O
+short	O
+gynecologic	O
+procedures	O
+under	O
+spinal	O
+anesthesia	O
+were	O
+randomly	O
+allocated	O
+to	O
+receive	O
+2	O
+.	O
+5	O
+ml	O
+2	O
+%	O
+lidocaine	B-Chemical
+in	O
+7	O
+.	O
+5	O
+%	O
+glucose	B-Chemical
+,	O
+2	O
+%	O
+prilocaine	B-Chemical
+in	O
+7	O
+.	O
+5	O
+%	O
+glucose	B-Chemical
+,	O
+or	O
+0	O
+.	O
+5	O
+%	O
+bupivacaine	B-Chemical
+in	O
+7	O
+.	O
+5	O
+%	O
+glucose	B-Chemical
+.	O
+
+All	O
+solutions	O
+were	O
+provided	O
+in	O
+blinded	O
+vials	O
+by	O
+the	O
+hospital	O
+pharmacy	O
+.	O
+
+Details	O
+of	O
+spinal	O
+puncture	O
+,	O
+extension	O
+and	O
+regression	O
+of	O
+spinal	O
+block	O
+,	O
+and	O
+the	O
+times	O
+to	O
+reach	O
+discharge	O
+criteria	O
+were	O
+noted	O
+.	O
+
+In	O
+the	O
+evening	O
+of	O
+postoperative	O
+day	O
+1	O
+,	O
+patients	O
+were	O
+evaluated	O
+for	O
+TNSs	B-Disease
+by	O
+a	O
+physician	O
+unaware	O
+of	O
+the	O
+drug	O
+administered	O
+and	O
+the	O
+details	O
+of	O
+the	O
+anesthetic	O
+procedure	O
+.	O
+
+RESULTS	O
+:	O
+Nine	O
+of	O
+30	O
+patients	O
+receiving	O
+lidocaine	B-Chemical
+experienced	O
+TNSs	B-Disease
+,	O
+1	O
+of	O
+30	O
+patients	O
+receiving	O
+prilocaine	B-Chemical
+(	O
+P	O
+=	O
+0	O
+.	O
+03	O
+)	O
+had	O
+them	O
+,	O
+and	O
+none	O
+of	O
+30	O
+patients	O
+receiving	O
+bupivacaine	B-Chemical
+had	O
+TNSs	B-Disease
+.	O
+
+Times	O
+to	O
+ambulate	O
+and	O
+to	O
+void	O
+were	O
+similar	O
+after	O
+lidocaine	B-Chemical
+and	O
+prilocaine	B-Chemical
+(	O
+150	O
+vs	O
+.	O
+165	O
+min	O
+and	O
+238	O
+vs	O
+.	O
+253	O
+min	O
+,	O
+respectively	O
+)	O
+but	O
+prolonged	O
+after	O
+bupivacaine	B-Chemical
+(	O
+200	O
+and	O
+299	O
+min	O
+,	O
+respectively	O
+;	O
+P	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+Prilocaine	B-Chemical
+may	O
+be	O
+preferable	O
+to	O
+lidocaine	B-Chemical
+for	O
+short	O
+surgical	O
+procedures	O
+because	O
+it	O
+has	O
+a	O
+similar	O
+duration	O
+of	O
+action	O
+but	O
+a	O
+lower	O
+incidence	O
+of	O
+TNSs	B-Disease
+.	O
+
+Suxamethonium	B-Chemical
+-	O
+induced	O
+cardiac	B-Disease
+arrest	I-Disease
+and	O
+death	B-Disease
+following	O
+5	O
+days	O
+of	O
+immobilization	O
+.	O
+
+The	O
+present	O
+report	O
+describes	O
+a	O
+case	O
+of	O
+cardiac	B-Disease
+arrest	I-Disease
+and	O
+subsequent	O
+death	B-Disease
+as	O
+a	O
+result	O
+of	O
+hyperkalaemia	B-Disease
+following	O
+the	O
+use	O
+of	O
+suxamethonium	B-Chemical
+in	O
+a	O
+23	O
+-	O
+year	O
+-	O
+old	O
+Malawian	O
+woman	O
+.	O
+
+Five	O
+days	O
+after	O
+the	O
+onset	O
+of	O
+the	O
+symptoms	O
+of	O
+meningitis	B-Disease
+,	O
+the	O
+patient	O
+aspirated	O
+stomach	O
+contents	O
+and	O
+needed	O
+endotracheal	O
+intubation	O
+.	O
+
+Forty	O
+seconds	O
+after	O
+injection	O
+of	O
+suxamethonium	B-Chemical
+,	O
+bradycardia	B-Disease
+and	O
+cardiac	B-Disease
+arrest	I-Disease
+occurred	O
+.	O
+
+Attempts	O
+to	O
+resuscitate	O
+the	O
+patient	O
+were	O
+not	O
+successful	O
+.	O
+
+The	O
+serum	O
+level	O
+of	O
+potassium	B-Chemical
+was	O
+observed	O
+to	O
+be	O
+8	O
+.	O
+4	O
+mequiv	O
+L	O
+-	O
+1	O
+.	O
+
+Apart	O
+from	O
+the	O
+reduction	O
+in	O
+the	O
+patient	O
+'	O
+s	O
+level	O
+of	O
+consciousness	O
+,	O
+there	O
+were	O
+no	O
+signs	O
+of	O
+motor	O
+neurone	O
+damage	O
+or	O
+of	O
+any	O
+of	O
+the	O
+other	O
+known	O
+predisposing	O
+conditions	O
+for	O
+hyperkalaemia	B-Disease
+following	O
+the	O
+administration	O
+of	O
+suxamethonium	B-Chemical
+.	O
+
+It	O
+is	O
+postulated	O
+that	O
+her	O
+death	B-Disease
+was	O
+caused	O
+by	O
+hypersensitivity	B-Disease
+to	O
+suxamethonium	B-Chemical
+,	O
+associated	O
+with	O
+her	O
+5	O
+-	O
+day	O
+immobilization	O
+.	O
+
+Acute	O
+hepatitis	B-Disease
+,	O
+autoimmune	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+,	O
+and	O
+erythroblastocytopenia	B-Disease
+induced	O
+by	O
+ceftriaxone	B-Chemical
+.	O
+
+An	O
+80	O
+-	O
+yr	O
+-	O
+old	O
+man	O
+developed	O
+acute	O
+hepatitis	B-Disease
+shortly	O
+after	O
+ingesting	O
+oral	O
+ceftriaxone	B-Chemical
+.	O
+
+Although	O
+the	O
+transaminases	O
+gradually	O
+returned	O
+to	O
+baseline	O
+after	O
+withholding	O
+the	O
+beta	B-Chemical
+lactam	I-Chemical
+antibiotic	O
+,	O
+there	O
+was	O
+a	O
+gradual	O
+increase	O
+in	O
+serum	O
+bilirubin	B-Chemical
+and	O
+a	O
+decrease	O
+in	O
+hemoglobin	O
+concentration	O
+caused	O
+by	O
+an	O
+autoimmune	B-Disease
+hemolytic	I-Disease
+anemia	I-Disease
+and	O
+erythroblastocytopenia	B-Disease
+.	O
+
+These	O
+responded	O
+to	O
+systemic	O
+steroids	B-Chemical
+and	O
+immunoglobulins	O
+.	O
+
+Despite	O
+the	O
+widespread	O
+use	O
+of	O
+these	O
+agents	O
+this	O
+triad	O
+of	O
+side	O
+effects	O
+has	O
+not	O
+previously	O
+been	O
+reported	O
+in	O
+connection	O
+with	O
+beta	B-Chemical
+lactam	I-Chemical
+antibiotics	O
+.	O
+
+Thyroxine	B-Chemical
+abuse	O
+:	O
+an	O
+unusual	O
+case	O
+of	O
+thyrotoxicosis	B-Disease
+in	O
+pregnancy	O
+.	O
+
+Eating	B-Disease
+disorders	I-Disease
+and	O
+the	O
+associated	O
+behavioural	O
+problems	O
+and	O
+drug	B-Disease
+abuse	I-Disease
+are	O
+uncommon	O
+in	O
+pregnancy	O
+.	O
+
+When	O
+they	O
+do	O
+occur	O
+they	O
+are	O
+often	O
+unrecognized	O
+because	O
+of	O
+denial	O
+but	O
+when	O
+significant	O
+may	O
+pose	O
+a	O
+risk	O
+to	O
+both	O
+the	O
+mother	O
+and	O
+her	O
+fetus	O
+.	O
+
+This	O
+case	O
+illustrates	O
+a	O
+number	O
+of	O
+problems	O
+that	O
+may	O
+be	O
+encountered	O
+in	O
+women	O
+with	O
+eating	B-Disease
+disorders	I-Disease
+in	O
+pregnancy	O
+,	O
+including	O
+prolonged	O
+and	O
+recurrent	O
+metabolic	O
+disturbances	O
+and	O
+diuretic	O
+abuse	O
+.	O
+
+In	O
+particular	O
+it	O
+illustrates	O
+the	O
+derangements	O
+of	O
+thyroid	O
+function	O
+seen	O
+in	O
+pregnant	O
+women	O
+with	O
+eating	B-Disease
+disorders	I-Disease
+and	O
+reminds	O
+us	O
+that	O
+when	O
+a	O
+cause	O
+for	O
+thyrotoxicosis	B-Disease
+remains	O
+obscure	O
+,	O
+thyroxine	B-Chemical
+abuse	O
+should	O
+be	O
+considered	O
+and	O
+explored	O
+.	O
+
+Repeated	O
+trimipramine	B-Chemical
+induces	O
+dopamine	B-Chemical
+D2	O
+/	O
+D3	O
+and	O
+alpha1	O
+-	O
+adrenergic	O
+up	O
+-	O
+regulation	O
+.	O
+
+Trimipramine	B-Chemical
+(	O
+TRI	B-Chemical
+)	O
+,	O
+which	O
+shows	O
+a	O
+clinical	O
+antidepressant	B-Chemical
+activity	O
+,	O
+is	O
+chemically	O
+related	O
+to	O
+imipramine	B-Chemical
+but	O
+does	O
+not	O
+inhibit	O
+the	O
+reuptake	O
+of	O
+noradrenaline	B-Chemical
+and	O
+5	B-Chemical
+-	I-Chemical
+hydroxytryptamine	I-Chemical
+,	O
+nor	O
+does	O
+it	O
+induce	O
+beta	O
+-	O
+adrenergic	O
+down	O
+-	O
+regulation	O
+.	O
+
+The	O
+mechanism	O
+of	O
+its	O
+antidepressant	B-Chemical
+activity	O
+is	O
+still	O
+unknown	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+find	O
+out	O
+whether	O
+TRI	B-Chemical
+given	O
+repeatedly	O
+was	O
+able	O
+to	O
+induce	O
+adaptive	O
+changes	O
+in	O
+the	O
+dopaminergic	O
+and	O
+alpha1	O
+-	O
+adrenergic	O
+systems	O
+,	O
+demonstrated	O
+by	O
+us	O
+previously	O
+for	O
+various	O
+antidepressants	B-Chemical
+.	O
+
+TRI	B-Chemical
+was	O
+given	O
+to	O
+male	O
+Wistar	O
+rats	O
+and	O
+male	O
+Albino	O
+Swiss	O
+mice	O
+perorally	O
+twice	O
+daily	O
+for	O
+14	O
+days	O
+.	O
+
+In	O
+the	O
+acute	O
+experiment	O
+TRI	B-Chemical
+(	O
+given	O
+i	O
+.	O
+p	O
+.	O
+)	O
+does	O
+not	O
+antagonize	O
+the	O
+reserpine	B-Chemical
+hypothermia	B-Disease
+in	O
+mice	O
+and	O
+does	O
+not	O
+potentiate	O
+the	O
+5	B-Chemical
+-	I-Chemical
+hydroxytryptophan	I-Chemical
+head	O
+twitches	O
+in	O
+rats	O
+.	O
+
+TRI	B-Chemical
+given	O
+repeatedly	O
+to	O
+rats	O
+increases	O
+the	O
+locomotor	O
+hyperactivity	B-Disease
+induced	O
+by	O
+d	B-Chemical
+-	I-Chemical
+amphetamine	I-Chemical
+,	O
+quinpirole	B-Chemical
+and	O
+(	O
++	O
+)	O
+-	O
+7	O
+-	O
+hydroxy	O
+-	O
+dipropyloaminotetralin	O
+(	O
+dopamine	B-Chemical
+D2	O
+and	O
+D3	O
+effects	O
+)	O
+.	O
+
+The	O
+stereotypies	O
+induced	O
+by	O
+d	B-Chemical
+-	I-Chemical
+amphetamine	I-Chemical
+or	O
+apomorphine	B-Chemical
+are	O
+not	O
+potentiated	O
+by	O
+TRI	B-Chemical
+.	O
+
+It	O
+increases	O
+the	O
+behaviour	O
+stimulation	O
+evoked	O
+by	O
+phenylephrine	B-Chemical
+(	O
+given	O
+intraventricularly	O
+)	O
+in	O
+rats	O
+,	O
+evaluated	O
+in	O
+the	O
+open	O
+field	O
+test	O
+as	O
+well	O
+as	O
+the	O
+aggressiveness	B-Disease
+evoked	O
+by	O
+clonidine	B-Chemical
+in	O
+mice	O
+,	O
+both	O
+these	O
+effects	O
+being	O
+mediated	O
+by	O
+an	O
+alpha1	O
+-	O
+adrenergic	O
+receptor	O
+.	O
+
+It	O
+may	O
+be	O
+concluded	O
+that	O
+,	O
+like	O
+other	O
+tricyclic	O
+antidepressants	B-Chemical
+studied	O
+previously	O
+,	O
+TRI	B-Chemical
+given	O
+repeatedly	O
+increases	O
+the	O
+responsiveness	O
+of	O
+brain	O
+dopamine	B-Chemical
+D2	O
+and	O
+D3	O
+(	O
+locomotor	O
+activity	O
+but	O
+not	O
+stereotypy	O
+)	O
+as	O
+well	O
+as	O
+alpha1	O
+-	O
+adrenergic	O
+receptors	O
+to	O
+their	O
+agonists	O
+.	O
+
+A	O
+question	O
+arises	O
+whether	O
+the	O
+reuptake	O
+inhibition	O
+is	O
+of	O
+any	O
+importance	O
+to	O
+the	O
+adaptive	O
+changes	O
+induced	O
+by	O
+repeated	O
+antidepressants	B-Chemical
+,	O
+suggested	O
+to	O
+be	O
+responsible	O
+for	O
+the	O
+antidepressant	B-Chemical
+activity	O
+.	O
+
+Pethidine	B-Chemical
+-	O
+associated	O
+seizure	B-Disease
+in	O
+a	O
+healthy	O
+adolescent	O
+receiving	O
+pethidine	B-Chemical
+for	O
+postoperative	B-Disease
+pain	I-Disease
+control	O
+.	O
+
+A	O
+healthy	O
+17	O
+-	O
+year	O
+-	O
+old	O
+male	O
+received	O
+standard	O
+intermittent	O
+doses	O
+of	O
+pethidine	B-Chemical
+via	O
+a	O
+patient	O
+-	O
+controlled	O
+analgesia	O
+(	O
+PCA	O
+)	O
+pump	O
+for	O
+management	O
+of	O
+postoperative	B-Disease
+pain	I-Disease
+control	O
+.	O
+
+Twenty	O
+-	O
+three	O
+h	O
+postoperatively	O
+he	O
+developed	O
+a	O
+brief	O
+self	O
+-	O
+limited	O
+seizure	B-Disease
+.	O
+
+Both	O
+plasma	O
+pethidine	B-Chemical
+and	O
+norpethidine	B-Chemical
+were	O
+elevated	O
+in	O
+the	O
+range	O
+associated	O
+with	O
+clinical	O
+manifestations	O
+of	O
+central	O
+nervous	O
+system	O
+excitation	O
+.	O
+
+No	O
+other	O
+risk	O
+factors	O
+for	O
+CNS	O
+toxicity	B-Disease
+were	O
+identified	O
+.	O
+
+This	O
+method	O
+allowed	O
+frequent	O
+self	O
+-	O
+dosing	O
+of	O
+pethidine	B-Chemical
+at	O
+short	O
+time	O
+intervals	O
+and	O
+rapid	O
+accumulation	O
+of	O
+pethidine	B-Chemical
+and	O
+norpethidine	B-Chemical
+.	O
+
+The	O
+routine	O
+use	O
+of	O
+pethidine	B-Chemical
+via	O
+PCA	O
+even	O
+for	O
+a	O
+brief	O
+postoperative	O
+analgesia	O
+should	O
+be	O
+reconsidered	O
+.	O
+
+An	O
+unusual	O
+toxic	O
+reaction	O
+to	O
+axillary	O
+block	O
+by	O
+mepivacaine	B-Chemical
+with	O
+adrenaline	B-Chemical
+.	O
+
+An	O
+increase	B-Disease
+in	I-Disease
+blood	I-Disease
+pressure	I-Disease
+,	O
+accompanied	O
+by	O
+atrial	B-Disease
+fibrillation	I-Disease
+,	O
+agitation	B-Disease
+,	O
+incomprehensible	B-Disease
+shouts	I-Disease
+and	O
+loss	B-Disease
+of	I-Disease
+consciousness	I-Disease
+,	O
+was	O
+observed	O
+in	O
+an	O
+elderly	O
+,	O
+ASA	O
+classification	O
+group	O
+II	O
+,	O
+cardiovascularly	O
+medicated	O
+male	O
+,	O
+12	O
+min	O
+after	O
+performance	O
+of	O
+axillary	O
+block	O
+with	O
+mepivacaine	B-Chemical
+850	O
+mg	O
+containing	O
+adrenaline	B-Chemical
+0	O
+.	O
+225	O
+mg	O
+,	O
+for	O
+correction	O
+of	O
+Dupuytren	B-Disease
+'	I-Disease
+s	I-Disease
+contracture	I-Disease
+.	O
+
+After	O
+intravenous	O
+administration	O
+of	O
+labetalol	B-Chemical
+,	O
+metoprolol	B-Chemical
+and	O
+midazolam	B-Chemical
+the	O
+patient	O
+'	O
+s	O
+condition	O
+improved	O
+,	O
+and	O
+15	O
+min	O
+later	O
+he	O
+woke	O
+up	O
+.	O
+
+The	O
+block	O
+was	O
+successful	O
+and	O
+surgery	O
+was	O
+conducted	O
+as	O
+scheduled	O
+despite	O
+persisting	O
+atrial	B-Disease
+fibrillation	I-Disease
+.	O
+
+Postoperatively	O
+,	O
+the	O
+patient	O
+refused	O
+DC	O
+cardioversion	O
+and	O
+was	O
+treated	O
+medically	O
+.	O
+
+Both	O
+the	O
+temporal	O
+relationship	O
+of	O
+events	O
+and	O
+the	O
+response	O
+to	O
+treatment	O
+suggest	O
+that	O
+a	O
+rapid	O
+systemic	O
+absorption	O
+of	O
+mepivacaine	B-Chemical
+with	O
+adrenaline	B-Chemical
+and	O
+/	O
+or	O
+interaction	O
+of	O
+these	O
+drugs	O
+with	O
+the	O
+patient	O
+'	O
+s	O
+cardiovascular	O
+medications	O
+were	O
+responsible	O
+for	O
+the	O
+perioperative	O
+complications	O
+.	O
+
+Drug	O
+-	O
+associated	O
+acute	O
+-	O
+onset	O
+vanishing	B-Disease
+bile	I-Disease
+duct	I-Disease
+and	O
+Stevens	B-Disease
+-	I-Disease
+Johnson	I-Disease
+syndromes	I-Disease
+in	O
+a	O
+child	O
+.	O
+
+Acute	O
+vanishing	B-Disease
+bile	I-Disease
+duct	I-Disease
+syndrome	O
+is	O
+a	O
+rare	O
+but	O
+established	O
+cause	O
+of	O
+progressive	O
+cholestasis	B-Disease
+in	O
+adults	O
+,	O
+is	O
+most	O
+often	O
+drug	O
+or	O
+toxin	O
+related	O
+,	O
+and	O
+is	O
+of	O
+unknown	O
+pathogenesis	O
+.	O
+
+It	O
+has	O
+not	O
+been	O
+reported	O
+previously	O
+in	O
+children	O
+.	O
+
+Stevens	B-Disease
+-	I-Disease
+Johnson	I-Disease
+syndrome	I-Disease
+is	O
+a	O
+well	O
+-	O
+recognized	O
+immune	O
+complex	O
+-	O
+mediated	O
+hypersensitivity	B-Disease
+reaction	O
+that	O
+affects	O
+all	O
+age	O
+groups	O
+,	O
+is	O
+drug	O
+or	O
+infection	B-Disease
+induced	O
+,	O
+and	O
+has	O
+classic	O
+systemic	O
+,	O
+mucosal	O
+,	O
+and	O
+dermatologic	O
+manifestations	O
+.	O
+
+A	O
+previously	O
+healthy	O
+child	O
+who	O
+developed	O
+acute	O
+,	O
+severe	O
+,	O
+rapidly	O
+progressive	O
+vanishing	B-Disease
+bile	I-Disease
+duct	I-Disease
+syndrome	I-Disease
+shortly	O
+after	O
+Stevens	B-Disease
+-	I-Disease
+Johnson	I-Disease
+syndrome	I-Disease
+is	O
+described	O
+;	O
+this	O
+was	O
+temporally	O
+associated	O
+with	O
+ibuprofen	B-Chemical
+use	O
+.	O
+
+Despite	O
+therapy	O
+with	O
+ursodeoxycholic	B-Chemical
+acid	I-Chemical
+,	O
+prednisone	B-Chemical
+,	O
+and	O
+then	O
+tacrolimus	B-Chemical
+,	O
+her	O
+cholestatic	B-Disease
+disease	I-Disease
+was	O
+unrelenting	O
+,	O
+with	O
+cirrhosis	B-Disease
+shown	O
+by	O
+biopsy	O
+6	O
+months	O
+after	O
+presentation	O
+.	O
+
+This	O
+case	O
+documents	O
+acute	O
+drug	O
+-	O
+related	O
+vanishing	B-Disease
+bile	I-Disease
+duct	I-Disease
+syndrome	I-Disease
+in	O
+the	O
+pediatric	O
+age	O
+group	O
+and	O
+suggests	O
+shared	O
+immune	O
+mechanisms	O
+in	O
+the	O
+pathogenesis	O
+of	O
+both	O
+Stevens	B-Disease
+-	I-Disease
+Johnson	I-Disease
+syndrome	I-Disease
+and	O
+vanishing	B-Disease
+bile	I-Disease
+duct	I-Disease
+syndrome	I-Disease
+.	O
+
+High	O
+incidence	O
+of	O
+primary	B-Disease
+pulmonary	I-Disease
+hypertension	I-Disease
+associated	O
+with	O
+appetite	B-Chemical
+suppressants	I-Chemical
+in	O
+Belgium	O
+.	O
+
+Primary	B-Disease
+pulmonary	I-Disease
+hypertension	I-Disease
+is	O
+a	O
+rare	O
+,	O
+progressive	O
+and	O
+incurable	O
+disease	O
+,	O
+which	O
+has	O
+been	O
+associated	O
+with	O
+the	O
+intake	O
+of	O
+appetite	B-Chemical
+suppressant	I-Chemical
+drugs	O
+.	O
+
+The	O
+importance	O
+of	O
+this	O
+association	O
+was	O
+evaluated	O
+in	O
+Belgium	O
+while	O
+this	O
+country	O
+still	O
+had	O
+no	O
+restriction	O
+on	O
+the	O
+prescription	O
+of	O
+appetite	B-Chemical
+suppressants	I-Chemical
+.	O
+
+Thirty	O
+-	O
+five	O
+patients	O
+with	O
+primary	B-Disease
+pulmonary	I-Disease
+hypertension	I-Disease
+and	O
+85	O
+matched	O
+controls	O
+were	O
+recruited	O
+over	O
+32	O
+months	O
+(	O
+1992	O
+-	O
+1994	O
+)	O
+in	O
+Belgium	O
+.	O
+
+Exposure	O
+to	O
+appetite	B-Chemical
+-	I-Chemical
+suppressants	I-Chemical
+was	O
+assessed	O
+on	O
+the	O
+basis	O
+of	O
+hospital	O
+records	O
+and	O
+standardized	O
+interview	O
+.	O
+
+Twenty	O
+-	O
+three	O
+of	O
+the	O
+patients	O
+had	O
+previously	O
+taken	O
+appetite	B-Chemical
+suppressants	I-Chemical
+,	O
+mainly	O
+fenfluramines	B-Chemical
+,	O
+as	O
+compared	O
+with	O
+only	O
+5	O
+of	O
+the	O
+controls	O
+(	O
+66	O
+versus	O
+6	O
+%	O
+,	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+.	O
+
+Five	O
+patients	O
+died	O
+before	O
+the	O
+interview	O
+,	O
+all	O
+of	O
+them	O
+had	O
+taken	O
+appetite	B-Chemical
+suppressants	I-Chemical
+.	O
+
+In	O
+8	O
+patients	O
+the	O
+diagnosis	O
+of	O
+primary	B-Disease
+pulmonary	I-Disease
+hypertension	I-Disease
+was	O
+uncertain	O
+,	O
+5	O
+of	O
+them	O
+had	O
+taken	O
+appetite	B-Chemical
+suppressants	I-Chemical
+.	O
+
+The	O
+patients	O
+who	O
+had	O
+been	O
+exposed	O
+to	O
+appetite	B-Chemical
+suppressants	I-Chemical
+tended	O
+to	O
+be	O
+on	O
+average	O
+more	O
+severely	O
+ill	O
+,	O
+and	O
+to	O
+have	O
+a	O
+shorter	O
+median	O
+delay	O
+between	O
+onset	O
+of	O
+symptoms	O
+and	O
+diagnosis	O
+.	O
+
+A	O
+policy	O
+of	O
+unrestricted	O
+prescription	O
+of	O
+appetite	B-Chemical
+suppressants	I-Chemical
+may	O
+lead	O
+to	O
+a	O
+high	O
+incidence	O
+of	O
+associated	O
+primary	B-Disease
+pulmonary	I-Disease
+hypertension	I-Disease
+.	O
+
+Intake	O
+of	O
+appetite	B-Chemical
+suppressants	I-Chemical
+may	O
+accelerate	O
+the	O
+progression	O
+of	O
+the	O
+disease	O
+.	O
+
+Inappropriate	O
+use	O
+of	O
+carbamazepine	B-Chemical
+and	O
+vigabatrin	B-Chemical
+in	O
+typical	O
+absence	B-Disease
+seizures	I-Disease
+.	O
+
+Carbamazepine	B-Chemical
+and	O
+vigabatrin	B-Chemical
+are	O
+contraindicated	O
+in	O
+typical	O
+absence	B-Disease
+seizures	I-Disease
+.	O
+
+Of	O
+18	O
+consecutive	O
+referrals	O
+of	O
+children	O
+with	O
+resistant	O
+typical	O
+absences	O
+only	O
+,	O
+eight	O
+were	O
+erroneously	O
+treated	O
+with	O
+carbamazepine	B-Chemical
+either	O
+as	O
+monotherapy	O
+or	O
+as	O
+an	O
+add	O
+-	O
+on	O
+.	O
+
+Vigabatrin	B-Chemical
+was	O
+also	O
+used	O
+in	O
+the	O
+treatment	O
+of	O
+two	O
+children	O
+.	O
+
+Frequency	O
+of	O
+absences	O
+increased	O
+in	O
+four	O
+children	O
+treated	O
+with	O
+carbamazepine	B-Chemical
+and	O
+two	O
+of	O
+these	O
+developed	O
+myoclonic	B-Disease
+jerks	I-Disease
+,	O
+which	O
+resolved	O
+on	O
+withdrawal	O
+of	O
+carbamazepine	B-Chemical
+.	O
+
+Absences	O
+were	O
+aggravated	O
+in	O
+both	O
+cases	O
+where	O
+vigabatrin	B-Chemical
+was	O
+added	O
+on	O
+to	O
+concurrent	O
+treatment	O
+.	O
+
+Optimal	O
+control	O
+of	O
+the	O
+absences	O
+was	O
+achieved	O
+with	O
+sodium	B-Chemical
+valproate	I-Chemical
+,	O
+lamotrigine	B-Chemical
+,	O
+or	O
+ethosuximide	B-Chemical
+alone	O
+or	O
+in	O
+combination	O
+.	O
+
+Choreoathetoid	B-Disease
+movements	I-Disease
+associated	O
+with	O
+rapid	O
+adjustment	O
+to	O
+methadone	B-Chemical
+.	O
+
+Choreatiform	B-Disease
+hyperkinesias	I-Disease
+are	O
+known	O
+to	O
+be	O
+occasional	O
+movement	B-Disease
+abnormalities	I-Disease
+during	O
+intoxications	O
+with	O
+cocaine	B-Chemical
+but	O
+not	O
+opiates	O
+.	O
+
+This	O
+is	O
+a	O
+case	O
+report	O
+of	O
+euphoria	O
+and	O
+choreoathetoid	B-Disease
+movements	I-Disease
+both	O
+transiently	O
+induced	O
+by	O
+rapid	O
+adjustment	O
+to	O
+the	O
+selective	O
+mu	O
+-	O
+opioid	O
+receptor	O
+agonist	O
+methadone	B-Chemical
+in	O
+an	O
+inpatient	O
+previously	O
+abusing	O
+heroine	B-Chemical
+and	O
+cocaine	B-Chemical
+.	O
+
+In	O
+addition	O
+,	O
+minor	O
+EEG	O
+abnormalities	O
+occurred	O
+.	O
+
+Possible	O
+underlying	O
+neurobiological	O
+phenomena	O
+are	O
+discussed	O
+.	O
+
+Adverse	O
+effects	O
+of	O
+the	O
+atypical	O
+antipsychotics	O
+.	O
+
+Collaborative	O
+Working	O
+Group	O
+on	O
+Clinical	O
+Trial	O
+Evaluations	O
+.	O
+
+Adverse	O
+effects	O
+of	O
+antipsychotics	O
+often	O
+lead	O
+to	O
+noncompliance	O
+.	O
+
+Thus	O
+,	O
+clinicians	O
+should	O
+address	O
+patients	O
+'	O
+concerns	O
+about	O
+adverse	O
+effects	O
+and	O
+attempt	O
+to	O
+choose	O
+medications	O
+that	O
+will	O
+improve	O
+their	O
+patients	O
+'	O
+quality	O
+of	O
+life	O
+as	O
+well	O
+as	O
+overall	O
+health	O
+.	O
+
+The	O
+side	O
+effect	O
+profiles	O
+of	O
+the	O
+atypical	O
+antipsychotics	O
+are	O
+more	O
+advantageous	O
+than	O
+those	O
+of	O
+the	O
+conventional	O
+neuroleptics	O
+.	O
+
+Conventional	O
+agents	O
+are	O
+associated	O
+with	O
+unwanted	O
+central	O
+nervous	O
+system	O
+effects	O
+,	O
+including	O
+extrapyramidal	B-Disease
+symptoms	I-Disease
+(	O
+EPS	B-Disease
+)	O
+,	O
+tardive	B-Disease
+dyskinesia	I-Disease
+,	O
+sedation	O
+,	O
+and	O
+possible	O
+impairment	O
+of	O
+some	O
+cognitive	O
+measures	O
+,	O
+as	O
+well	O
+as	O
+cardiac	O
+effects	O
+,	O
+orthostatic	B-Disease
+hypotension	I-Disease
+,	O
+hepatic	O
+changes	O
+,	O
+anticholinergic	O
+side	O
+effects	O
+,	O
+sexual	B-Disease
+dysfunction	I-Disease
+,	O
+and	O
+weight	B-Disease
+gain	I-Disease
+.	O
+
+The	O
+newer	O
+atypical	O
+agents	O
+have	O
+a	O
+lower	O
+risk	O
+of	O
+EPS	B-Disease
+,	O
+but	O
+are	O
+associated	O
+in	O
+varying	O
+degrees	O
+with	O
+sedation	O
+,	O
+cardiovascular	O
+effects	O
+,	O
+anticholinergic	O
+effects	O
+,	O
+weight	B-Disease
+gain	I-Disease
+,	O
+sexual	B-Disease
+dysfunction	I-Disease
+,	O
+hepatic	O
+effects	O
+,	O
+lowered	O
+seizure	B-Disease
+threshold	O
+(	O
+primarily	O
+clozapine	B-Chemical
+)	O
+,	O
+and	O
+agranulocytosis	B-Disease
+(	O
+clozapine	B-Chemical
+only	O
+)	O
+.	O
+
+Since	O
+the	O
+incidence	O
+and	O
+severity	O
+of	O
+specific	O
+adverse	O
+effects	O
+differ	O
+among	O
+the	O
+various	O
+atypicals	O
+,	O
+the	O
+clinician	O
+should	O
+carefully	O
+consider	O
+which	O
+side	O
+effects	O
+are	O
+most	O
+likely	O
+to	O
+lead	O
+to	O
+the	O
+individual	O
+'	O
+s	O
+dissatisfaction	O
+and	O
+noncompliance	O
+before	O
+choosing	O
+an	O
+antipsychotic	O
+for	O
+a	O
+particular	O
+patient	O
+.	O
+
+A	O
+randomized	O
+,	O
+placebo	O
+-	O
+controlled	O
+dose	O
+-	O
+comparison	O
+trial	O
+of	O
+haloperidol	B-Chemical
+for	O
+psychosis	B-Disease
+and	O
+disruptive	B-Disease
+behaviors	I-Disease
+in	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+OBJECTIVE	O
+:	O
+The	O
+goal	O
+of	O
+this	O
+study	O
+was	O
+to	O
+compare	O
+the	O
+efficacy	O
+and	O
+side	O
+effects	O
+of	O
+two	O
+doses	O
+of	O
+haloperidol	B-Chemical
+and	O
+placebo	O
+in	O
+the	O
+treatment	O
+of	O
+psychosis	B-Disease
+and	O
+disruptive	B-Disease
+behaviors	I-Disease
+in	O
+patients	O
+with	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+METHOD	O
+:	O
+In	O
+a	O
+6	O
+-	O
+week	O
+random	O
+-	O
+assignment	O
+,	O
+double	O
+-	O
+blind	O
+,	O
+placebo	O
+-	O
+controlled	O
+trial	O
+(	O
+phase	O
+A	O
+)	O
+,	O
+haloperidol	B-Chemical
+,	O
+2	O
+-	O
+3	O
+mg	O
+/	O
+day	O
+(	O
+standard	O
+dose	O
+)	O
+,	O
+and	O
+haloperidol	B-Chemical
+,	O
+0	O
+.	O
+50	O
+-	O
+0	O
+.	O
+75	O
+mg	O
+/	O
+day	O
+(	O
+low	O
+dose	O
+)	O
+,	O
+were	O
+compared	O
+in	O
+71	O
+outpatients	O
+with	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+.	O
+
+For	O
+the	O
+subsequent	O
+6	O
+-	O
+week	O
+double	O
+-	O
+blind	O
+crossover	O
+phase	O
+(	O
+phase	O
+B	O
+)	O
+,	O
+patients	O
+taking	O
+standard	O
+-	O
+or	O
+low	O
+-	O
+dose	O
+haloperidol	B-Chemical
+were	O
+switched	O
+to	O
+placebo	O
+,	O
+and	O
+patients	O
+taking	O
+placebo	O
+were	O
+randomly	O
+assigned	O
+to	O
+standard	O
+-	O
+or	O
+low	O
+-	O
+dose	O
+haloperidol	B-Chemical
+.	O
+
+RESULTS	O
+:	O
+For	O
+the	O
+60	O
+patients	O
+who	O
+completed	O
+phase	O
+A	O
+,	O
+standard	O
+-	O
+dose	O
+haloperidol	B-Chemical
+was	O
+efficacious	O
+and	O
+superior	O
+to	O
+both	O
+low	O
+-	O
+dose	O
+haloperidol	B-Chemical
+and	O
+placebo	O
+for	O
+scores	O
+on	O
+the	O
+Brief	O
+Psychiatric	O
+Rating	O
+Scale	O
+psychosis	B-Disease
+factor	O
+and	O
+on	O
+psychomotor	B-Disease
+agitation	I-Disease
+.	O
+
+Response	O
+rates	O
+according	O
+to	O
+three	O
+sets	O
+of	O
+criteria	O
+were	O
+greater	O
+with	O
+the	O
+standard	O
+dose	O
+(	O
+55	O
+%	O
+-	O
+60	O
+%	O
+)	O
+than	O
+the	O
+low	O
+dose	O
+(	O
+25	O
+%	O
+-	O
+35	O
+%	O
+)	O
+and	O
+placebo	O
+(	O
+25	O
+%	O
+-	O
+30	O
+%	O
+)	O
+.	O
+
+The	O
+advantage	O
+of	O
+standard	O
+dose	O
+over	O
+low	O
+dose	O
+was	O
+replicated	O
+in	O
+phase	O
+B	O
+.	O
+
+In	O
+phase	O
+A	O
+,	O
+extrapyramidal	B-Disease
+signs	I-Disease
+tended	O
+to	O
+be	O
+greater	O
+with	O
+the	O
+standard	O
+dose	O
+than	O
+in	O
+the	O
+other	O
+two	O
+conditions	O
+,	O
+primarily	O
+because	O
+of	O
+a	O
+subgroup	O
+(	O
+20	O
+%	O
+)	O
+who	O
+developed	O
+moderate	O
+to	O
+severe	O
+signs	O
+.	O
+
+Low	O
+-	O
+dose	O
+haloperidol	B-Chemical
+did	O
+not	O
+differ	O
+from	O
+placebo	O
+on	O
+any	O
+measure	O
+of	O
+efficacy	O
+or	O
+side	O
+effects	O
+.	O
+
+CONCLUSIONS	O
+:	O
+The	O
+results	O
+indicated	O
+a	O
+favorable	O
+therapeutic	O
+profile	O
+for	O
+haloperidol	B-Chemical
+in	O
+doses	O
+of	O
+2	O
+-	O
+3	O
+mg	O
+/	O
+day	O
+,	O
+although	O
+a	O
+subgroup	O
+developed	O
+moderate	O
+to	O
+severe	O
+extrapyramidal	B-Disease
+signs	I-Disease
+.	O
+
+A	O
+starting	O
+dose	O
+of	O
+1	O
+mg	O
+/	O
+day	O
+with	O
+gradual	O
+,	O
+upward	O
+dose	O
+titration	O
+is	O
+recommended	O
+.	O
+
+The	O
+narrow	O
+therapeutic	O
+window	O
+observed	O
+with	O
+haloperidol	B-Chemical
+may	O
+also	O
+apply	O
+to	O
+other	O
+neuroleptics	O
+used	O
+in	O
+Alzheimer	B-Disease
+'	I-Disease
+s	I-Disease
+disease	I-Disease
+patients	O
+with	O
+psychosis	B-Disease
+and	O
+disruptive	B-Disease
+behaviors	I-Disease
+.	O
+
+Effects	O
+of	O
+acetylsalicylic	B-Chemical
+acid	I-Chemical
+,	O
+dipyridamole	B-Chemical
+,	O
+and	O
+hydrocortisone	B-Chemical
+on	O
+epinephrine	B-Chemical
+-	O
+induced	O
+myocardial	B-Disease
+injury	I-Disease
+in	O
+dogs	O
+.	O
+
+A	O
+reproducible	O
+model	O
+for	O
+producing	O
+diffuse	O
+myocardial	B-Disease
+injury	I-Disease
+(	O
+epinephrine	B-Chemical
+infusion	O
+)	O
+has	O
+been	O
+developed	O
+to	O
+study	O
+the	O
+cardioprotective	O
+effects	O
+of	O
+agents	O
+or	O
+maneuvers	O
+which	O
+might	O
+alter	O
+the	O
+evolution	O
+of	O
+acute	O
+myocardial	B-Disease
+infarction	I-Disease
+.	O
+
+Infusions	O
+of	O
+epinephrine	B-Chemical
+(	O
+4	O
+mug	O
+per	O
+kilogram	O
+per	O
+minute	O
+for	O
+6	O
+hours	O
+)	O
+increased	O
+radiocalcium	B-Chemical
+uptakes	O
+into	O
+intact	O
+myocardium	O
+and	O
+each	O
+of	O
+its	O
+subcellular	O
+components	O
+with	O
+the	O
+mitochondrial	O
+fraction	O
+showing	O
+the	O
+most	O
+consistent	O
+changes	O
+when	O
+compared	O
+to	O
+saline	O
+-	O
+infused	O
+control	O
+animals	O
+(	O
+4	O
+,	O
+957	O
+vs	O
+.	O
+827	O
+counts	O
+per	O
+minute	O
+per	O
+gram	O
+of	O
+dried	O
+tissue	O
+or	O
+fraction	O
+)	O
+.	O
+
+Myocardial	O
+concentrations	O
+of	O
+calcium	B-Chemical
+also	O
+increased	O
+significantly	O
+(	O
+12	O
+.	O
+0	O
+vs	O
+.	O
+5	O
+.	O
+0	O
+mg	O
+.	O
+per	O
+100	O
+Gm	O
+.	O
+of	O
+fat	O
+-	O
+free	O
+dry	O
+weight	O
+)	O
+.	O
+
+Infusions	O
+of	O
+calcium	B-Chemical
+chloride	I-Chemical
+sufficient	O
+to	O
+raise	O
+serum	O
+calcium	B-Chemical
+concentrations	O
+2	O
+mEq	O
+.	O
+per	O
+liter	O
+failed	O
+to	O
+increase	O
+calcium	B-Chemical
+influx	O
+into	O
+the	O
+myocardial	O
+cell	O
+.	O
+
+Mitochondrial	O
+radiocalcium	B-Chemical
+uptakes	O
+were	O
+significantly	O
+decreased	O
+in	O
+animals	O
+pretreated	O
+with	O
+acetylsalicylic	B-Chemical
+acid	I-Chemical
+or	O
+dipyridamole	B-Chemical
+or	O
+when	O
+hydrocortisone	B-Chemical
+was	O
+added	O
+to	O
+the	O
+epinephrine	B-Chemical
+infusion	O
+(	O
+2	O
+,	O
+682	O
+,	O
+2	O
+,	O
+803	O
+,	O
+and	O
+3	O
+,	O
+424	O
+counts	O
+per	O
+minute	O
+per	O
+gram	O
+of	O
+dried	O
+fraction	O
+,	O
+respectively	O
+)	O
+.	O
+
+Myocardial	O
+calcium	B-Chemical
+concentrations	O
+also	O
+were	O
+decreased	O
+(	O
+11	O
+.	O
+2	O
+,	O
+8	O
+.	O
+3	O
+,	O
+and	O
+8	O
+.	O
+9	O
+mg	O
+.	O
+per	O
+100	O
+Gm	O
+.	O
+of	O
+fat	O
+-	O
+free	O
+dry	O
+weight	O
+,	O
+respectively	O
+)	O
+in	O
+the	O
+three	O
+treatment	O
+groups	O
+,	O
+being	O
+significantly	O
+decreased	O
+only	O
+in	O
+the	O
+last	O
+two	O
+.	O
+
+Evidence	O
+of	O
+microscopic	O
+damage	O
+was	O
+graded	O
+as	O
+less	O
+severe	O
+in	O
+the	O
+three	O
+treatment	O
+groups	O
+.	O
+
+Acetylsalicylic	B-Chemical
+acid	I-Chemical
+,	O
+dipyridamole	B-Chemical
+,	O
+and	O
+hydrocortisone	B-Chemical
+all	O
+appear	O
+to	O
+have	O
+cardioprotective	O
+effects	O
+when	O
+tested	O
+in	O
+this	O
+model	O
+.	O
+
+Clinical	O
+and	O
+histopathologic	O
+examination	O
+of	O
+renal	O
+allografts	O
+treated	O
+with	O
+tacrolimus	B-Chemical
+(	O
+FK506	B-Chemical
+)	O
+for	O
+at	O
+least	O
+one	O
+year	O
+.	O
+
+BACKGROUND	O
+:	O
+We	O
+clinically	O
+and	O
+pathologically	O
+analyzed	O
+renal	O
+allografts	O
+from	O
+1	O
+9	O
+renal	O
+transplant	O
+patients	O
+treated	O
+with	O
+tacrolimus	B-Chemical
+(	O
+FK506	B-Chemical
+)	O
+for	O
+more	O
+than	O
+1	O
+year	O
+.	O
+
+METHODS	O
+:	O
+Twenty	O
+-	O
+six	O
+renal	O
+allograft	O
+biopsy	O
+specimens	O
+from	O
+1	O
+9	O
+renal	O
+transplant	O
+patients	O
+who	O
+underwent	O
+transplantations	O
+between	O
+1991	O
+and	O
+1993	O
+were	O
+evaluated	O
+.	O
+
+Thirteen	O
+biopsies	O
+were	O
+performed	O
+from	O
+stable	O
+functioning	O
+renal	O
+allografts	O
+with	O
+informed	O
+consent	O
+(	O
+nonepisode	O
+biopsy	O
+)	O
+and	O
+the	O
+other	O
+13	O
+were	O
+from	O
+dysfunctional	O
+renal	O
+allografts	O
+with	O
+a	O
+clinical	O
+indication	O
+for	O
+biopsy	O
+(	O
+episode	O
+biopsy	O
+)	O
+.	O
+
+RESULTS	O
+:	O
+The	O
+main	O
+pathologic	O
+diagnoses	O
+(	O
+some	O
+overlap	O
+)	O
+were	O
+acute	O
+rejection	O
+(	O
+AR	O
+;	O
+n	O
+=	O
+4	O
+)	O
+,	O
+chronic	O
+rejection	O
+(	O
+CR	O
+;	O
+n	O
+=	O
+5	O
+)	O
+,	O
+AR	O
++	O
+CR	O
+(	O
+n	O
+=	O
+4	O
+)	O
+,	O
+recurrent	O
+IgA	B-Disease
+nephropathy	I-Disease
+(	O
+n	O
+=	O
+5	O
+)	O
+,	O
+normal	O
+findings	O
+(	O
+n	O
+=	O
+2	O
+)	O
+,	O
+minimal	O
+-	O
+type	O
+chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+(	O
+n	O
+=	O
+9	O
+)	O
+,	O
+and	O
+mild	O
+-	O
+type	O
+FK506	B-Chemical
+nephropathy	B-Disease
+(	O
+n	O
+=	O
+11	O
+)	O
+.	O
+
+Of	O
+the	O
+nonepisode	O
+biopsies	O
+,	O
+7	O
+and	O
+4	O
+biopsies	O
+showed	O
+minimal	O
+-	O
+type	O
+and	O
+mild	O
+-	O
+type	O
+chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+,	O
+respectively	O
+.	O
+
+Chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+consisted	O
+of	O
+rough	O
+and	O
+foamy	O
+tubular	O
+vacuolization	O
+(	O
+5	O
+biopsies	O
+)	O
+,	O
+arteriolopathy	O
+(	O
+angiodegeneration	O
+of	O
+the	O
+arteriolar	O
+wall	O
+;	O
+20	O
+biopsies	O
+)	O
+,	O
+focal	B-Disease
+segmental	I-Disease
+glomerulosclerosis	I-Disease
+(	O
+4	O
+biopsies	O
+)	O
+and	O
+the	O
+striped	O
+form	O
+of	O
+interstitial	B-Disease
+fibrosis	I-Disease
+(	O
+11	O
+biopsies	O
+)	O
+.	O
+
+The	O
+serum	O
+creatinine	B-Chemical
+levels	O
+of	O
+patients	O
+in	O
+the	O
+mild	O
+-	O
+type	O
+chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+group	O
+,	O
+which	O
+included	O
+7	O
+episode	O
+biopsies	O
+,	O
+were	O
+statistically	O
+higher	O
+than	O
+those	O
+in	O
+the	O
+minimum	O
+-	O
+type	O
+chronic	O
+FK506	B-Chemical
+-	O
+nephropathy	B-Disease
+group	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+CONCLUSIONS	O
+:	O
+This	O
+study	O
+demonstrates	O
+that	O
+chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+consists	O
+primarily	O
+of	O
+arteriolopathy	O
+manifesting	O
+as	O
+insudative	O
+hyalinosis	O
+of	O
+the	O
+arteriolar	O
+wall	O
+,	O
+and	O
+suggests	O
+that	O
+mild	O
+-	O
+type	O
+chronic	O
+FK506	B-Chemical
+nephropathy	B-Disease
+is	O
+a	O
+condition	O
+which	O
+may	O
+lead	O
+to	O
+deterioration	O
+of	O
+renal	O
+allograft	O
+function	O
+.	O
+
+Different	O
+lobular	O
+distributions	O
+of	O
+altered	O
+hepatocyte	O
+tight	O
+junctions	O
+in	O
+rat	O
+models	O
+of	O
+intrahepatic	B-Disease
+and	I-Disease
+extrahepatic	I-Disease
+cholestasis	I-Disease
+.	O
+
+Hepatocyte	O
+tight	O
+junctions	O
+(	O
+TJs	O
+)	O
+,	O
+the	O
+only	O
+intercellular	O
+barrier	O
+between	O
+the	O
+sinusoidal	O
+and	O
+the	O
+canalicular	O
+spaces	O
+,	O
+play	O
+a	O
+key	O
+role	O
+in	O
+bile	O
+formation	O
+.	O
+
+Although	O
+hepatocyte	O
+TJs	O
+are	O
+impaired	O
+in	O
+cholestasis	B-Disease
+,	O
+attempts	O
+to	O
+localize	O
+the	O
+precise	O
+site	O
+of	O
+hepatocyte	O
+TJ	O
+damage	O
+by	O
+freeze	O
+-	O
+fracture	O
+electron	O
+microscopy	O
+have	O
+produced	O
+limited	O
+information	O
+.	O
+
+Recently	O
+,	O
+several	O
+TJ	O
+-	O
+associated	O
+proteins	O
+like	O
+ZO	O
+-	O
+1	O
+and	O
+7H6	O
+have	O
+been	O
+identified	O
+and	O
+characterized	O
+.	O
+
+Immunolocalization	O
+of	O
+7H6	O
+appears	O
+to	O
+closely	O
+correlate	O
+with	O
+paracellular	O
+permeability	O
+.	O
+
+We	O
+used	O
+rat	O
+models	O
+of	O
+intrahepatic	B-Disease
+cholestasis	I-Disease
+by	O
+ethinyl	B-Chemical
+estradiol	I-Chemical
+(	O
+EE	B-Chemical
+)	O
+treatment	O
+and	O
+extrahepatic	B-Disease
+cholestasis	I-Disease
+by	O
+bile	O
+duct	O
+ligation	O
+(	O
+BDL	O
+)	O
+to	O
+precisely	O
+determine	O
+the	O
+site	O
+of	O
+TJ	O
+damage	O
+.	O
+
+Alterations	O
+in	O
+hepatocyte	O
+TJs	O
+were	O
+assessed	O
+by	O
+double	O
+-	O
+immunolabeling	O
+for	O
+7H6	O
+and	O
+ZO	O
+-	O
+1	O
+using	O
+a	O
+confocal	O
+laser	O
+scanning	O
+microscope	O
+.	O
+
+In	O
+control	O
+rats	O
+,	O
+immunostaining	O
+for	O
+7H6	O
+and	O
+ZO	O
+-	O
+1	O
+colocalized	O
+to	O
+outline	O
+bile	O
+canaliculi	O
+in	O
+a	O
+continuous	O
+fashion	O
+.	O
+
+In	O
+contrast	O
+,	O
+7H6	O
+and	O
+ZO	O
+-	O
+1	O
+immunostaining	O
+was	O
+more	O
+discontinuous	O
+,	O
+outlining	O
+the	O
+bile	O
+canaliculi	O
+after	O
+BDL	O
+.	O
+
+Immunostaining	O
+for	O
+7H6	O
+,	O
+not	O
+ZO	O
+-	O
+1	O
+,	O
+decreased	O
+and	O
+predominantly	O
+appeared	O
+as	O
+discrete	O
+signals	O
+in	O
+the	O
+submembranous	O
+cytoplasm	O
+of	O
+periportal	O
+hepatocytes	O
+after	O
+BDL	O
+.	O
+
+After	O
+EE	B-Chemical
+treatment	O
+,	O
+changes	O
+in	O
+immunostaining	O
+for	O
+7H6	O
+and	O
+ZO	O
+-	O
+1	O
+were	O
+similar	O
+to	O
+those	O
+seen	O
+in	O
+periportal	O
+hepatocytes	O
+after	O
+BDL	O
+,	O
+but	O
+distributed	O
+more	O
+diffusely	O
+throughout	O
+the	O
+lobule	O
+.	O
+
+This	O
+study	O
+is	O
+the	O
+first	O
+to	O
+demonstrate	O
+that	O
+impairment	O
+of	O
+hepatocyte	O
+TJs	O
+occurs	O
+heterogenously	O
+in	O
+the	O
+liver	O
+lobule	O
+after	O
+BDL	O
+and	O
+suggests	O
+that	O
+BDL	O
+and	O
+EE	B-Chemical
+treatments	O
+produce	O
+different	O
+lobular	O
+distributions	O
+of	O
+increased	O
+paracellular	O
+permeability	O
+.	O
+
+Memory	O
+facilitation	O
+and	O
+stimulation	O
+of	O
+endogenous	O
+nerve	O
+growth	O
+factor	O
+synthesis	O
+by	O
+the	O
+acetylcholine	B-Chemical
+releaser	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+.	O
+
+The	O
+effects	O
+of	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+(	O
+3alpha	B-Chemical
+-	I-Chemical
+tropyl	I-Chemical
+2	I-Chemical
+-	I-Chemical
+(	I-Chemical
+p	I-Chemical
+-	I-Chemical
+bromophenyl	I-Chemical
+)	I-Chemical
+propionate	I-Chemical
+)	O
+,	O
+the	O
+acetylcholine	B-Chemical
+releaser	O
+,	O
+on	O
+memory	O
+processes	O
+and	O
+nerve	O
+growth	O
+factor	O
+(	O
+NGF	O
+)	O
+synthesis	O
+were	O
+evaluated	O
+.	O
+
+In	O
+the	O
+mouse	O
+passive	O
+-	O
+avoidance	O
+test	O
+,	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+(	O
+10	O
+-	O
+30	O
+mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+p	O
+.	O
+)	O
+,	O
+administered	O
+20	O
+min	O
+before	O
+the	O
+training	O
+session	O
+,	O
+prevented	O
+amnesia	B-Disease
+induced	O
+by	O
+both	O
+the	O
+non	O
+selective	O
+antimuscarinic	O
+drug	O
+scopolamine	B-Chemical
+and	O
+the	O
+M1	O
+-	O
+selective	O
+antagonist	O
+S	B-Chemical
+-	I-Chemical
+(	I-Chemical
+-	I-Chemical
+)	I-Chemical
+-	I-Chemical
+ET	I-Chemical
+-	I-Chemical
+126	I-Chemical
+.	O
+
+In	O
+the	O
+same	O
+experimental	O
+conditions	O
+,	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+(	O
+5	O
+-	O
+20	O
+microg	O
+per	O
+mouse	O
+,	O
+i	O
+.	O
+c	O
+.	O
+v	O
+.	O
+)	O
+was	O
+also	O
+able	O
+to	O
+prevent	O
+antimuscarine	O
+-	O
+induced	O
+amnesia	B-Disease
+,	O
+demonstrating	O
+a	O
+central	O
+localization	O
+of	O
+the	O
+activity	O
+.	O
+
+At	O
+the	O
+highest	O
+effective	O
+doses	O
+,	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+did	O
+not	O
+produce	O
+any	O
+collateral	O
+symptoms	O
+as	O
+revealed	O
+by	O
+the	O
+Irwin	O
+test	O
+,	O
+and	O
+it	O
+did	O
+not	O
+modify	O
+spontaneous	O
+motility	O
+and	O
+inspection	O
+activity	O
+,	O
+as	O
+revealed	O
+by	O
+the	O
+hole	O
+-	O
+board	O
+test	O
+.	O
+
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+was	O
+also	O
+able	O
+to	O
+increase	O
+the	O
+amount	O
+of	O
+NGF	O
+secreted	O
+in	O
+vitro	O
+by	O
+astrocytes	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+.	O
+
+The	O
+maximal	O
+NGF	O
+contents	O
+obtained	O
+by	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+were	O
+17	O
+.	O
+6	O
+-	O
+fold	O
+of	O
+the	O
+control	O
+value	O
+.	O
+
+During	O
+culture	O
+,	O
+no	O
+morphological	O
+changes	O
+were	O
+found	O
+at	O
+effective	O
+concentrations	O
+of	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+.	O
+
+The	O
+current	O
+work	O
+indicates	O
+the	O
+ability	O
+of	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+to	O
+induce	O
+beneficial	O
+effects	O
+on	O
+cognitive	O
+processes	O
+and	O
+stimulate	O
+activity	O
+of	O
+NGF	O
+synthesis	O
+in	O
+astroglial	O
+cells	O
+.	O
+
+Therefore	O
+,	O
+PG	B-Chemical
+-	I-Chemical
+9	I-Chemical
+could	O
+represent	O
+a	O
+potential	O
+useful	O
+drug	O
+able	O
+to	O
+improve	O
+the	O
+function	O
+of	O
+impaired	O
+cognitive	O
+processes	O
+.	O
+
+Mechanisms	O
+of	O
+FK	B-Chemical
+506	I-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+in	O
+the	O
+rat	O
+.	O
+
+-	O
+Tacrolimus	B-Chemical
+(	O
+FK	B-Chemical
+506	I-Chemical
+)	O
+is	O
+a	O
+powerful	O
+,	O
+widely	O
+used	O
+immunosuppressant	O
+.	O
+
+The	O
+clinical	O
+utility	O
+of	O
+FK	B-Chemical
+506	I-Chemical
+is	O
+complicated	O
+by	O
+substantial	O
+hypertension	B-Disease
+and	O
+nephrotoxicity	B-Disease
+.	O
+
+To	O
+clarify	O
+the	O
+mechanisms	O
+of	O
+FK	B-Chemical
+506	I-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+,	O
+we	O
+studied	O
+the	O
+chronic	O
+effects	O
+of	O
+FK	B-Chemical
+506	I-Chemical
+on	O
+the	O
+synthesis	O
+of	O
+endothelin	O
+-	O
+1	O
+(	O
+ET	O
+-	O
+1	O
+)	O
+,	O
+the	O
+expression	O
+of	O
+mRNA	O
+of	O
+ET	O
+-	O
+1	O
+and	O
+endothelin	O
+-	O
+converting	O
+enzyme	O
+-	O
+1	O
+(	O
+ECE	O
+-	O
+1	O
+)	O
+,	O
+the	O
+endothelial	O
+nitric	B-Chemical
+oxide	I-Chemical
+synthase	O
+(	O
+eNOS	O
+)	O
+activity	O
+,	O
+and	O
+the	O
+expression	O
+of	O
+mRNA	O
+of	O
+eNOS	O
+and	O
+C	O
+-	O
+type	O
+natriuretic	O
+peptide	O
+(	O
+CNP	O
+)	O
+in	O
+rat	O
+blood	O
+vessels	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+effect	O
+of	O
+the	O
+specific	O
+endothelin	O
+type	O
+A	O
+receptor	O
+antagonist	O
+FR	B-Chemical
+139317	I-Chemical
+on	O
+FK	B-Chemical
+506	I-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+in	O
+rats	O
+was	O
+studied	O
+.	O
+
+FK	B-Chemical
+506	I-Chemical
+,	O
+5	O
+mg	O
+.	O
+
+kg	O
+-	O
+1	O
+.	O
+
+d	O
+-	O
+1	O
+given	O
+for	O
+4	O
+weeks	O
+,	O
+elevated	O
+blood	O
+pressure	O
+from	O
+102	O
++	O
+/	O
+-	O
+13	O
+to	O
+152	O
++	O
+/	O
+-	O
+15	O
+mm	O
+Hg	O
+and	O
+increased	O
+the	O
+synthesis	O
+of	O
+ET	O
+-	O
+1	O
+and	O
+the	O
+levels	O
+of	O
+ET	O
+-	O
+1	O
+mRNA	O
+in	O
+the	O
+mesenteric	O
+artery	O
+(	O
+240	O
+%	O
+and	O
+230	O
+%	O
+,	O
+respectively	O
+)	O
+.	O
+
+Little	O
+change	O
+was	O
+observed	O
+in	O
+the	O
+expression	O
+of	O
+ECE	O
+-	O
+1	O
+mRNA	O
+and	O
+CNP	O
+mRNA	O
+.	O
+
+FK	B-Chemical
+506	I-Chemical
+decreased	O
+eNOS	O
+activity	O
+and	O
+the	O
+levels	O
+of	O
+eNOS	O
+mRNA	O
+in	O
+the	O
+aorta	O
+(	O
+48	O
+%	O
+and	O
+55	O
+%	O
+,	O
+respectively	O
+)	O
+.	O
+
+The	O
+administration	O
+of	O
+FR	B-Chemical
+139317	I-Chemical
+(	O
+10	O
+mg	O
+.	O
+kg	O
+-	O
+1	O
+.	O
+d	O
+-	O
+1	O
+)	O
+prevented	O
+FK	B-Chemical
+506	I-Chemical
+-	O
+induced	O
+hypertension	B-Disease
+in	O
+rats	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+FK	B-Chemical
+506	I-Chemical
+may	O
+increase	O
+blood	O
+pressure	O
+not	O
+only	O
+by	O
+increasing	O
+ET	O
+-	O
+1	O
+production	O
+but	O
+also	O
+by	O
+decreasing	O
+NO	B-Chemical
+synthesis	O
+in	O
+the	O
+vasculature	O
+.	O
+
+Scp160p	O
+,	O
+a	O
+multiple	O
+KH	O
+-	O
+domain	O
+protein	O
+,	O
+is	O
+a	O
+component	O
+of	O
+mRNP	O
+complexes	O
+in	O
+yeast	B
+
+Abstract	O
+
+Scp160p	O
+is	O
+a	O
+160	O
+kDa	O
+protein	O
+in	O
+the	O
+yeast	B
+Saccharomyces	B
+cerevisiae	I
+that	O
+contains	O
+14	O
+repeats	O
+of	O
+the	O
+hnRNP	O
+K	O
+-	O
+homology	O
+(	O
+KH	O
+)	O
+domain	O
+,	O
+and	O
+demonstrates	O
+significant	O
+sequence	O
+homology	O
+to	O
+a	O
+family	O
+of	O
+proteins	O
+collectively	O
+known	O
+as	O
+vigilins	O
+.	O
+
+As	O
+a	O
+first	O
+step	O
+towards	O
+defining	O
+the	O
+function	O
+of	O
+Scp160p	O
+,	O
+we	O
+have	O
+characterized	O
+the	O
+subcellular	O
+distribution	O
+and	O
+in	O
+vivo	O
+interactions	O
+of	O
+this	O
+protein	O
+.	O
+
+Using	O
+sucrose	O
+gradient	O
+fractionation	O
+studies	O
+we	O
+have	O
+demonstrated	O
+that	O
+Scp160p	O
+in	O
+cytoplasmic	O
+lysates	O
+is	O
+predominantly	O
+associated	O
+with	O
+polyribosomes	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+have	O
+found	O
+that	O
+Scp160p	O
+is	O
+released	O
+from	O
+polyribosomes	O
+by	O
+EDTA	O
+in	O
+the	O
+form	O
+of	O
+a	O
+large	O
+complex	O
+of	O
+>	O
+=	O
+1300	O
+kDa	O
+that	O
+is	O
+sensitive	O
+both	O
+to	O
+RNase	O
+and	O
+NaCl	O
+.	O
+
+Using	O
+affinity	O
+-	O
+chromatography	O
+to	O
+isolate	O
+these	O
+complexes	O
+,	O
+we	O
+have	O
+identified	O
+two	O
+protein	O
+components	O
+other	O
+than	O
+Scp160p	O
+:	O
+poly	O
+(	O
+A	O
+)	O
+binding	O
+protein	O
+,	O
+Pab1p	O
+,	O
+and	O
+Bfr1p	O
+.	O
+
+The	O
+presence	O
+of	O
+Pab1p	O
+confirms	O
+these	O
+complexes	O
+to	O
+be	O
+mRNPs	O
+.	O
+
+The	O
+presence	O
+of	O
+Bfr1p	O
+is	O
+intriguing	O
+because	O
+the	O
+null	O
+phenotype	O
+for	O
+this	O
+gene	O
+is	O
+essentially	O
+the	O
+same	O
+as	O
+that	O
+reported	O
+for	O
+scp160	O
+-	O
+null	O
+cells	O
+:	O
+increased	O
+cell	O
+size	O
+and	O
+aberrant	O
+DNA	O
+content	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+Scp160p	O
+associates	O
+with	O
+polyribosome	O
+-	O
+bound	O
+mRNP	O
+complexes	O
+in	O
+vivo	O
+,	O
+implicating	O
+a	O
+role	O
+for	O
+this	O
+protein	O
+in	O
+one	O
+or	O
+more	O
+levels	O
+of	O
+mRNA	O
+metabolism	O
+in	O
+yeast	B
+.	O
+
+INTRODUCTION	O
+
+Scp160p	O
+is	O
+a	O
+1222	O
+amino	O
+acid	O
+Saccharomyces	B
+cerevisiae	I
+protein	O
+that	O
+contains	O
+14	O
+copies	O
+of	O
+the	O
+hnRNP	O
+K	O
+homology	O
+(	O
+KH	O
+)	O
+domain	O
+,	O
+a	O
+highly	O
+conserved	O
+motif	O
+found	O
+in	O
+many	O
+proteins	O
+involved	O
+in	O
+RNA	O
+metabolism	O
+(	O
+1	O
+)	O
+.	O
+
+KH	O
+domain	O
+-	O
+containing	O
+proteins	O
+appear	O
+to	O
+have	O
+diverse	O
+functions	O
+and	O
+have	O
+been	O
+identified	O
+in	O
+all	O
+kingdoms	O
+of	O
+life	O
+,	O
+including	O
+the	O
+ribosomal	O
+protein	O
+S3	O
+from	O
+Escherichia	B
+coli	I
+(	O
+1	O
+)	O
+,	O
+Mer1p	O
+from	O
+S	B
+.	I
+cerevisiae	I
+,	O
+a	O
+meiosis	O
+-	O
+specific	O
+splicing	O
+factor	O
+(	O
+1	O
+)	O
+,	O
+MEX	O
+-	O
+3	O
+from	O
+Caenorhabditis	B
+elegans	I
+,	O
+presumably	O
+involved	O
+in	O
+mRNA	O
+localization	O
+during	O
+development	O
+(	O
+2	O
+)	O
+,	O
+and	O
+FMRP	O
+,	O
+the	O
+fragile	O
+-	O
+X	O
+mental	O
+retardation	O
+protein	O
+in	O
+humans	B
+(	O
+3	O
+)	O
+.	O
+
+A	O
+partial	O
+clone	O
+of	O
+Scp160p	O
+,	O
+known	O
+as	O
+HX	O
+,	O
+was	O
+one	O
+of	O
+the	O
+first	O
+multiple	O
+-	O
+KH	O
+proteins	O
+identified	O
+(	O
+1	O
+)	O
+.	O
+
+Whole	O
+cell	O
+immunofluorescence	O
+studies	O
+have	O
+demonstrated	O
+that	O
+Scp160p	O
+localizes	O
+to	O
+the	O
+cytoplasm	O
+,	O
+with	O
+enrichment	O
+around	O
+the	O
+nuclear	O
+envelope	O
+,	O
+and	O
+what	O
+appears	O
+to	O
+be	O
+the	O
+endoplasmic	O
+reticulum	O
+(	O
+3	O
+)	O
+.	O
+
+Deletion	O
+of	O
+the	O
+SCP160	O
+locus	O
+in	O
+yeast	B
+is	O
+not	O
+lethal	O
+,	O
+but	O
+results	O
+in	O
+a	O
+complex	O
+phenotype	O
+,	O
+including	O
+increased	O
+DNA	O
+content	O
+per	O
+cell	O
+,	O
+missegregation	O
+of	O
+genetic	O
+markers	O
+during	O
+sporulation	O
+,	O
+and	O
+abnormal	O
+cell	O
+morphology	O
+,	O
+including	O
+increased	O
+size	O
+and	O
+irregular	O
+shape	O
+(	O
+4	O
+)	O
+.	O
+
+Observation	O
+of	O
+this	O
+phenotype	O
+led	O
+to	O
+the	O
+hypothesis	O
+that	O
+Scp160p	O
+may	O
+function	O
+in	O
+regulating	O
+ploidy	O
+during	O
+cell	O
+division	O
+.	O
+
+More	O
+recently	O
+,	O
+Weber	O
+and	O
+colleagues	O
+demonstrated	O
+in	O
+vitro	O
+RNA	O
+binding	O
+activity	O
+of	O
+Scp160p	O
+using	O
+northwestern	O
+blot	O
+analyses	O
+;	O
+the	O
+protein	O
+was	O
+found	O
+to	O
+bind	O
+efficiently	O
+to	O
+ribohomopolymers	O
+and	O
+rRNA	O
+,	O
+but	O
+not	O
+to	O
+tRNA	O
+(	O
+5	O
+)	O
+.	O
+
+Cell	O
+fractionation	O
+studies	O
+revealed	O
+that	O
+a	O
+large	O
+percentage	O
+of	O
+Scp160p	O
+associates	O
+with	O
+membrane	O
+-	O
+pellets	O
+,	O
+and	O
+is	O
+released	O
+by	O
+treatment	O
+with	O
+either	O
+10	O
+mM	O
+EDTA	O
+or	O
+500	O
+mM	O
+NaCl	O
+(	O
+5	O
+)	O
+.	O
+
+While	O
+these	O
+authors	O
+interpreted	O
+these	O
+results	O
+to	O
+suggest	O
+that	O
+the	O
+nuclear	O
+envelope	O
+/	O
+ER	O
+localization	O
+of	O
+Scp160p	O
+was	O
+due	O
+primarily	O
+to	O
+interactions	O
+of	O
+the	O
+protein	O
+with	O
+membrane	O
+-	O
+bound	O
+polyribosomes	O
+,	O
+clear	O
+evidence	O
+of	O
+this	O
+association	O
+has	O
+not	O
+been	O
+reported	O
+(	O
+5	O
+)	O
+.	O
+
+Currently	O
+,	O
+the	O
+relationship	O
+between	O
+the	O
+phenotype	O
+of	O
+scp160	O
+null	O
+mutants	O
+and	O
+the	O
+RNA	O
+-	O
+binding	O
+activity	O
+of	O
+Scp160p	O
+remains	O
+unclear	O
+.	O
+
+Scp160p	O
+demonstrates	O
+significant	O
+sequence	O
+homology	O
+(	O
+~	O
+23	O
+%	O
+identity	O
+and	O
+~	O
+40	O
+%	O
+similarity	O
+at	O
+the	O
+amino	O
+acid	O
+level	O
+)	O
+to	O
+a	O
+class	O
+of	O
+vertebrate	O
+KH	O
+-	O
+domain	O
+proteins	O
+collectively	O
+known	O
+as	O
+vigilins	O
+.	O
+
+First	O
+identified	O
+in	O
+chicken	B
+,	O
+vigilin	O
+homologues	O
+have	O
+now	O
+been	O
+found	O
+in	O
+human	B
+(	O
+6	O
+)	O
+,	O
+Xenopus	B
+laevis	I
+(	O
+7	O
+)	O
+,	O
+Drosophila	B
+melanogaster	I
+(	O
+8	O
+)	O
+,	O
+C	B
+.	I
+elegans	I
+(	O
+5	O
+)	O
+and	O
+Schizosaccharomyces	B
+pombe	I
+.	O
+
+While	O
+all	O
+of	O
+the	O
+vigilin	O
+proteins	O
+studied	O
+to	O
+date	O
+are	O
+reported	O
+to	O
+bind	O
+nucleic	O
+acid	O
+,	O
+both	O
+the	O
+type	O
+of	O
+nucleic	O
+acid	O
+bound	O
+and	O
+the	O
+functional	O
+significance	O
+of	O
+these	O
+interactions	O
+remain	O
+unclear	O
+.	O
+
+For	O
+example	O
+,	O
+Kruse	O
+and	O
+colleagues	O
+reported	O
+from	O
+their	O
+work	O
+with	O
+human	B
+cells	O
+in	O
+culture	O
+that	O
+vigilin	O
+may	O
+be	O
+involved	O
+in	O
+the	O
+binding	O
+and	O
+transport	O
+of	O
+tRNA	O
+(	O
+9	O
+-	O
+11	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+Dodson	O
+and	O
+Shapiro	O
+concluded	O
+from	O
+their	O
+work	O
+with	O
+Xenopus	O
+vigilin	O
+that	O
+,	O
+in	O
+response	O
+to	O
+estrogen	O
+,	O
+the	O
+protein	O
+bound	O
+specifically	O
+to	O
+the	O
+3	O
+'	O
+UTR	O
+of	O
+vitellogenin	O
+mRNA	O
+(	O
+7	O
+,	O
+12	O
+)	O
+,	O
+potentially	O
+stabilizing	O
+the	O
+message	O
+(	O
+13	O
+)	O
+.	O
+
+Lastly	O
+,	O
+DDP1	O
+,	O
+the	O
+Drosophila	O
+homolog	O
+of	O
+vigilin	O
+,	O
+was	O
+reported	O
+recently	O
+to	O
+interact	O
+with	O
+the	O
+dodeca	O
+-	O
+satellite	O
+repeat	O
+regions	O
+of	O
+centromeric	O
+heterochromatin	O
+in	O
+embryonic	O
+and	O
+larval	O
+cell	O
+nuclei	O
+,	O
+suggesting	O
+a	O
+possible	O
+role	O
+for	O
+this	O
+protein	O
+in	O
+heterochromatin	O
+structure	O
+(	O
+8	O
+)	O
+.	O
+
+The	O
+goal	O
+of	O
+the	O
+present	O
+study	O
+was	O
+to	O
+begin	O
+elucidating	O
+the	O
+function	O
+of	O
+Scp160p	O
+in	O
+yeast	B
+by	O
+characterizing	O
+the	O
+subcellular	O
+distribution	O
+and	O
+macromolecular	O
+interactions	O
+of	O
+this	O
+protein	O
+.	O
+
+We	O
+have	O
+demonstrated	O
+that	O
+Scp160p	O
+in	O
+cytoplasmic	O
+lysates	O
+is	O
+associated	O
+predominantly	O
+with	O
+polyribosomes	O
+,	O
+and	O
+that	O
+following	O
+treatment	O
+with	O
+EDTA	O
+,	O
+Scp160p	O
+remains	O
+in	O
+an	O
+RNase	O
+/	O
+NaCl	O
+-	O
+sensitive	O
+complex	O
+of	O
+apparent	O
+molecular	O
+weight	O
+approximately	O
+>	O
+=	O
+1300	O
+kDa	O
+.	O
+
+Affinity	O
+purification	O
+of	O
+this	O
+complex	O
+revealed	O
+the	O
+presence	O
+of	O
+poly	O
+(	O
+A	O
+)	O
+-	O
+binding	O
+protein	O
+(	O
+Pab1p	O
+)	O
+,	O
+a	O
+well	O
+-	O
+characterized	O
+component	O
+of	O
+eukaryotic	O
+mRNPs	O
+(	O
+14	O
+,	O
+15	O
+)	O
+.	O
+
+Finally	O
+,	O
+a	O
+third	O
+abundant	O
+protein	O
+component	O
+of	O
+this	O
+complex	O
+was	O
+identified	O
+as	O
+Bfr1p	O
+,	O
+a	O
+protein	O
+not	O
+previously	O
+reported	O
+to	O
+associate	O
+with	O
+mRNPs	O
+.	O
+
+While	O
+the	O
+function	O
+of	O
+Bfr1p	O
+remains	O
+unknown	O
+,	O
+gene	O
+deletion	O
+reportedly	O
+leads	O
+to	O
+a	O
+phenotype	O
+remarkably	O
+similar	O
+to	O
+that	O
+of	O
+scp160	O
+deletion	O
+(	O
+16	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+a	O
+role	O
+for	O
+Scp160p	O
+in	O
+mRNA	O
+metabolism	O
+in	O
+yeast	B
+,	O
+and	O
+by	O
+extension	O
+,	O
+support	O
+results	O
+seen	O
+with	O
+Xenopus	O
+vigilin	O
+in	O
+its	O
+interactions	O
+with	O
+mRNA	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+the	O
+data	O
+reported	O
+here	O
+demonstrate	O
+Scp160p	O
+to	O
+be	O
+the	O
+first	O
+example	O
+of	O
+a	O
+KH	O
+-	O
+domain	O
+protein	O
+that	O
+functions	O
+as	O
+a	O
+component	O
+of	O
+polyribosome	O
+-	O
+associated	O
+mRNP	O
+complexes	O
+in	O
+the	O
+yeast	B
+,	O
+S	B
+.	I
+cerevisiae	I
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+
+Plasmids	O
+,	O
+yeast	B
+strains	O
+and	O
+culture	O
+conditions	O
+
+All	O
+recombinant	O
+DNA	O
+manipulations	O
+were	O
+performed	O
+according	O
+to	O
+standard	O
+techniques	O
+and	O
+utilized	O
+E	B
+.	I
+coli	I
+strain	O
+XL1	O
+-	O
+Blue	O
+(	O
+Stratagene	O
+)	O
+.	O
+
+The	O
+yeast	B
+strain	O
+JFy1511	O
+,	O
+expressing	O
+FLAG	O
+-	O
+Scp160p	O
+,	O
+was	O
+derived	O
+by	O
+two	O
+-	O
+step	O
+gene	O
+replacement	O
+from	O
+strain	O
+yJJ52	O
+(	O
+MAT	O
+alpha	O
+gal7	O
+Delta	O
+102	O
+ura3	O
+-	O
+52	O
+trp1	O
+-	O
+289	O
+ade1	O
+lys1	O
+leu2	O
+-	O
+3	O
+,	O
+112	O
+;	O
+generously	O
+donated	O
+by	O
+Drs	O
+Mark	O
+Parthun	O
+and	O
+Judith	O
+Jaehning	O
+,	O
+University	O
+of	O
+Colorado	O
+Health	O
+Sciences	O
+Center	O
+)	O
+,	O
+and	O
+confirmed	O
+by	O
+PCR	O
+.	O
+
+The	O
+wild	O
+-	O
+type	O
+SCP160	O
+coding	O
+sequence	O
+was	O
+obtained	O
+by	O
+PCR	O
+amplification	O
+from	O
+a	O
+genomic	O
+DNA	O
+preparation	O
+from	O
+yJFK1	O
+(	O
+MAT	O
+alpha	O
+gal7	O
+Delta	O
+102	O
+ura3	O
+-	O
+52	O
+trp1	O
+-	O
+289	O
+ade1	O
+lys1	O
+leu2	O
+-	O
+3	O
+,	O
+112	O
+Delta	O
+GAL80	O
+:	O
+:	O
+URA3	O
+)	O
+,	O
+using	O
+a	O
+16	O
+:	O
+1	O
+mixture	O
+of	O
+Taq	O
+(	O
+Fisher	O
+Biotech	O
+)	O
+and	O
+Pfu	O
+(	O
+Stratagene	O
+)	O
+DNA	O
+polymerases	O
+and	O
+the	O
+following	O
+primers	O
+:	O
+Scp160F1	O
+(	O
+5	O
+'	O
+-	O
+GCCGGTCGA	O
+-	O
+CTAACTGCAATGTCTGAAGA	O
+-	O
+3	O
+'	O
+)	O
+and	O
+Scp160R1	O
+(	O
+5	O
+'	O
+-	O
+GCGCGTCGACGAGCTTGTCT	O
+-	O
+CTTAAGG	O
+-	O
+3	O
+'	O
+)	O
+.	O
+
+A	O
+wild	O
+-	O
+type	O
+SCP160	O
+genomic	O
+clone	O
+,	O
+containing	O
+1	O
+kb	O
+upstream	O
+and	O
+300	O
+bp	O
+downstream	O
+sequence	O
+was	O
+PCR	O
+amplified	O
+from	O
+yJFK1	O
+genomic	O
+DNA	O
+using	O
+the	O
+primers	O
+Scp160F0	O
+(	O
+5	O
+'	O
+-	O
+GCCGAGCTCACACCAGCTTT	O
+-	O
+3	O
+'	O
+)	O
+and	O
+Scp160R2	O
+(	O
+5	O
+'	O
+-	O
+GCGCAAGCTTGTGCGGTA	O
+-	O
+TCCCAGTCTATG	O
+-	O
+3	O
+'	O
+)	O
+.	O
+
+The	O
+resultant	O
+clone	O
+was	O
+confirmed	O
+by	O
+dideoxy	O
+sequencing	O
+.	O
+
+The	O
+N	O
+-	O
+terminal	O
+FLAG	O
+and	O
+HA	O
+tags	O
+were	O
+added	O
+using	O
+PCR	O
+with	O
+the	O
+primers	O
+ScpFLAGF1	O
+(	O
+5	O
+'	O
+-	O
+CCAT	O
+-	O
+TATAACTGCAATGGACTACA	O
+-	O
+AAGATGTCTGAAGAACAAAC	O
+-	O
+3	O
+'	O
+)	O
+and	O
+ScpHAF1	O
+(	O
+5	O
+'	O
+-	O
+CCCCCTCCTGTCGACATTAT	O
+-	O
+TCACCATCACCATTCTGAAG	O
+-	O
+3	O
+'	O
+)	O
+respectively	O
+.	O
+
+For	O
+integration	O
+,	O
+constructs	O
+containing	O
+the	O
+1	O
+kb	O
+upstream	O
+and	O
+300	O
+bp	O
+downstream	O
+sequence	O
+were	O
+subcloned	O
+into	O
+the	O
+plasmid	O
+YIplac211	O
+(	O
+17	O
+)	O
+using	O
+SacI	O
+and	O
+HindIII	O
+restriction	O
+sites	O
+.	O
+
+The	O
+HA	O
+-	O
+tagged	O
+construct	O
+was	O
+subcloned	O
+into	O
+the	O
+low	O
+copy	O
+number	O
+plasmid	O
+,	O
+YCplac22	O
+using	O
+SacI	O
+and	O
+HindIII	O
+restriction	O
+sites	O
+.	O
+
+The	O
+SCP160	O
+deletion	O
+construct	O
+was	O
+made	O
+by	O
+removal	O
+of	O
+a	O
+3	O
+.	O
+4	O
+kb	O
+ApaI	O
+-	O
+KpnI	O
+fragment	O
+from	O
+the	O
+coding	O
+region	O
+of	O
+this	O
+construct	O
+,	O
+followed	O
+by	O
+treatment	O
+with	O
+Klenow	O
+fragment	O
+and	O
+re	O
+-	O
+ligation	O
+following	O
+attachment	O
+of	O
+BamHI	O
+linker	O
+oligonucleotides	O
+.	O
+
+Genomic	O
+integration	O
+of	O
+the	O
+plasmid	O
+sequences	O
+and	O
+subsequent	O
+removal	O
+of	O
+the	O
+endogenous	O
+SCP160	O
+allele	O
+were	O
+achieved	O
+by	O
+standard	O
+two	O
+-	O
+step	O
+gene	O
+replacement	O
+techniques	O
+(	O
+18	O
+)	O
+and	O
+confirmed	O
+by	O
+PCR	O
+.	O
+
+The	O
+N	O
+-	O
+terminally	O
+HA	O
+-	O
+tagged	O
+allele	O
+of	O
+BFR1	O
+was	O
+generated	O
+by	O
+PCR	O
+-	O
+amplifiction	O
+of	O
+the	O
+BFR1	O
+locus	O
+from	O
+wild	O
+-	O
+type	O
+(	O
+W303	O
+)	O
+yeast	B
+genomic	O
+DNA	O
+using	O
+the	O
+primers	O
+BFR1HAF1	O
+(	O
+5	O
+'	O
+-	O
+CCGCGGATCCATGTACC	O
+-	O
+CATACGACGTCCCAGACTAC	O
+-	O
+AACACAA	O
+-	O
+3	O
+'	O
+)	O
+and	O
+BFR1HINDR1	O
+(	O
+5	O
+'	O
+-	O
+CCGCAAGCTTGTCG	O
+-	O
+ACTATTTCATATGCCACAGG	O
+-	O
+3	O
+'	O
+)	O
+,	O
+and	O
+subcloned	O
+into	O
+YIPlac211	O
+.	O
+
+The	O
+BFR1	O
+promoter	O
+region	O
+was	O
+PCR	O
+-	O
+amplified	O
+in	O
+a	O
+similar	O
+manner	O
+using	O
+the	O
+primers	O
+BFR1SACF1	O
+(	O
+5	O
+'	O
+-	O
+CCGCGAG	O
+-	O
+CTCAGCATTAAGCATTCACG	O
+-	O
+3	O
+'	O
+)	O
+and	O
+BFR1BAMR1	O
+(	O
+5	O
+'	O
+-	O
+CCGCGGATCCGGCAATGGCT	O
+-	O
+3	O
+'	O
+)	O
+and	O
+subcloned	O
+into	O
+the	O
+appropriate	O
+position	O
+upstream	O
+of	O
+the	O
+HA	O
+-	O
+Bfr1p	O
+open	O
+reading	O
+frame	O
+in	O
+the	O
+plasmid	O
+backbone	O
+.	O
+
+The	O
+entire	O
+open	O
+reading	O
+frame	O
+was	O
+confirmed	O
+by	O
+dideoxy	O
+sequencing	O
+.	O
+
+Finally	O
+,	O
+the	O
+HA	O
+-	O
+BFR1	O
+allele	O
+was	O
+substituted	O
+into	O
+the	O
+yeast	B
+genome	O
+in	O
+place	O
+of	O
+the	O
+native	O
+allele	O
+using	O
+linearization	O
+with	O
+SphI	O
+and	O
+standard	O
+two	O
+-	O
+step	O
+gene	O
+replacement	O
+techniques	O
+.	O
+
+All	O
+yeast	B
+transformations	O
+and	O
+culture	O
+manipulations	O
+were	O
+performed	O
+according	O
+to	O
+standard	O
+protocols	O
+as	O
+described	O
+elsewhere	O
+(	O
+19	O
+)	O
+.	O
+
+Confirmation	O
+of	O
+genomic	O
+integrations	O
+
+All	O
+genomic	O
+integrations	O
+were	O
+confirmed	O
+by	O
+PCR	O
+amplifications	O
+from	O
+purified	O
+yeast	B
+genomic	O
+DNA	O
+.	O
+
+For	O
+scp160	O
+deletion	O
+mutants	O
+,	O
+the	O
+primers	O
+Scp160PF	O
+(	O
+5	O
+'	O
+-	O
+GATTTCCTAACTTTCC	O
+-	O
+GTCTA	O
+-	O
+3	O
+'	O
+)	O
+and	O
+Scp160R5	O
+(	O
+5	O
+'	O
+-	O
+GCGCAAGCTTCACCGCCTTA	O
+-	O
+3	O
+'	O
+)	O
+that	O
+flanked	O
+the	O
+deleted	O
+region	O
+were	O
+used	O
+.	O
+
+Similarly	O
+,	O
+epitope	O
+tags	O
+on	O
+Scp160p	O
+were	O
+confirmed	O
+by	O
+PCR	O
+using	O
+primers	O
+that	O
+flanked	O
+the	O
+tag	O
+sequence	O
+.	O
+
+Positive	O
+clones	O
+were	O
+further	O
+confirmed	O
+by	O
+western	O
+blot	O
+analysis	O
+of	O
+crude	O
+cell	O
+lysates	O
+using	O
+the	O
+appropriate	O
+anti	O
+-	O
+tag	O
+antibodies	O
+.	O
+
+The	O
+presence	O
+of	O
+HA	O
+-	O
+Bfr1p	O
+in	O
+cells	O
+was	O
+confirmed	O
+by	O
+western	O
+blot	O
+analysis	O
+of	O
+soluble	O
+cell	O
+lysates	O
+using	O
+12CA5	O
+mAb	O
+(	O
+Boehringer	O
+Mannheim	O
+)	O
+.	O
+
+Polyribosome	O
+isolation	O
+
+Polyribosomes	O
+were	O
+isolated	O
+using	O
+a	O
+combination	O
+of	O
+protocols	O
+described	O
+by	O
+Stansfield	O
+and	O
+colleagues	O
+(	O
+20	O
+)	O
+and	O
+by	O
+Dr	O
+Maurice	O
+Swanson	O
+(	O
+personal	O
+communication	O
+)	O
+.	O
+
+In	O
+brief	O
+,	O
+a	O
+100	O
+ml	O
+culture	O
+of	O
+yeast	B
+was	O
+grown	O
+in	O
+either	O
+YEPD	O
+or	O
+Hartwell	O
+synthetic	O
+medium	O
+,	O
+to	O
+early	O
+-	O
+log	O
+phase	O
+(	O
+OD600	O
+=	O
+1	O
+.	O
+0	O
+)	O
+,	O
+at	O
+which	O
+time	O
+cyclohexamide	O
+(	O
+Sigma	O
+)	O
+was	O
+added	O
+directly	O
+to	O
+the	O
+culture	O
+to	O
+a	O
+final	O
+concentration	O
+of	O
+100	O
+micro	O
+g	O
+/	O
+ml	O
+.	O
+
+The	O
+culture	O
+was	O
+incubated	O
+on	O
+ice	O
+for	O
+15	O
+min	O
+,	O
+and	O
+cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+4000	O
+r	O
+.	O
+p	O
+.	O
+m	O
+.	O
+/	O
+10	O
+min	O
+)	O
+.	O
+
+Following	O
+two	O
+washes	O
+in	O
+10	O
+ml	O
+of	O
+water	O
+containing	O
+100	O
+micro	O
+g	O
+/	O
+ml	O
+cyclohexamide	O
+,	O
+cells	O
+were	O
+lysed	O
+by	O
+vortex	O
+agitation	O
+with	O
+an	O
+equal	O
+volume	O
+of	O
+glass	O
+beads	O
+in	O
+1	O
+ml	O
+lysis	O
+buffer	O
+(	O
+25	O
+mM	O
+Tris	O
+pH	O
+7	O
+.	O
+2	O
+,	O
+50	O
+mM	O
+KCl	O
+,	O
+30	O
+mM	O
+MgCl2	O
+,	O
+5	O
+mM	O
+beta	O
+-	O
+mercaptoethanol	O
+,	O
+200	O
+micro	O
+g	O
+/	O
+ml	O
+cyclohexamide	O
+,	O
+2	O
+micro	O
+g	O
+/	O
+ml	O
+aprotonin	O
+,	O
+1	O
+mM	O
+PMSF	O
+,	O
+0	O
+.	O
+5	O
+micro	O
+g	O
+/	O
+ml	O
+leupeptin	O
+,	O
+2	O
+.	O
+9	O
+micro	O
+g	O
+/	O
+ml	O
+E64	O
+,	O
+1	O
+micro	O
+g	O
+/	O
+ml	O
+antipain	O
+,	O
+0	O
+.	O
+2	O
+micro	O
+g	O
+/	O
+ml	O
+chymostatin	O
+)	O
+.	O
+
+Lysate	O
+was	O
+transferred	O
+to	O
+a	O
+clean	O
+microfuge	O
+tube	O
+,	O
+and	O
+centrifuged	O
+10	O
+min	O
+at	O
+3000	O
+g	O
+at	O
+4	O
+degrees	O
+C	O
+.	O
+
+The	O
+supernatant	O
+was	O
+again	O
+transferred	O
+to	O
+a	O
+clean	O
+microfuge	O
+tube	O
+and	O
+centrifuged	O
+at	O
+12	O
+000	O
+g	O
+for	O
+15	O
+min	O
+at	O
+4	O
+degrees	O
+C	O
+,	O
+and	O
+then	O
+assayed	O
+for	O
+absorbance	O
+at	O
+260	O
+nm	O
+.	O
+
+Approximately	O
+12	O
+OD260	O
+units	O
+were	O
+loaded	O
+onto	O
+a	O
+11	O
+ml	O
+15	O
+-	O
+45	O
+%	O
+sucrose	O
+gradient	O
+made	O
+in	O
+10	O
+mM	O
+Tris	O
+,	O
+pH	O
+7	O
+.	O
+4	O
+,	O
+70	O
+mM	O
+NH4Cl	O
+,	O
+4	O
+mM	O
+MgOAc	O
+,	O
+using	O
+a	O
+Gradient	O
+Master	O
+automatic	O
+system	O
+,	O
+and	O
+the	O
+gradient	O
+was	O
+centrifuged	O
+in	O
+a	O
+SW41ti	O
+rotor	O
+(	O
+Beckman	O
+)	O
+at	O
+39	O
+000	O
+r	O
+.	O
+p	O
+.	O
+m	O
+.	O
+for	O
+2	O
+.	O
+5	O
+h	O
+.	O
+
+0	O
+.	O
+5	O
+ml	O
+fractions	O
+were	O
+collected	O
+using	O
+an	O
+Isco	O
+gradient	O
+fractionator	O
+,	O
+and	O
+gradient	O
+profiles	O
+were	O
+determined	O
+by	O
+monitoring	O
+absorbance	O
+at	O
+254	O
+nm	O
+.	O
+
+For	O
+EDTA	O
+controls	O
+,	O
+lysis	O
+buffer	O
+containing	O
+5	O
+mM	O
+MgCl2	O
+was	O
+used	O
+,	O
+and	O
+30	O
+mM	O
+EDTA	O
+was	O
+added	O
+to	O
+the	O
+sample	O
+before	O
+loading	O
+onto	O
+the	O
+gradient	O
+.	O
+
+Where	O
+indicated	O
+,	O
+addition	O
+of	O
+50	O
+U	O
+/	O
+ml	O
+of	O
+RNase	O
+One	O
+(	O
+Promega	O
+)	O
+was	O
+performed	O
+prior	O
+to	O
+loading	O
+the	O
+sample	O
+onto	O
+the	O
+gradient	O
+.	O
+
+Gel	O
+filtration	O
+chromatography	O
+
+Gel	O
+filtration	O
+chromatography	O
+was	O
+performed	O
+using	O
+a	O
+120	O
+ml	O
+Hi	O
+-	O
+Prep	O
+S	O
+-	O
+300	O
+Sephacryl	O
+column	O
+(	O
+Pharmacia	O
+)	O
+with	O
+a	O
+cut	O
+-	O
+off	O
+of	O
+1300	O
+kDa	O
+,	O
+attached	O
+to	O
+an	O
+FPLC	O
+system	O
+(	O
+Pharmacia	O
+)	O
+.	O
+
+The	O
+column	O
+had	O
+been	O
+calibrated	O
+previously	O
+using	O
+the	O
+following	O
+molecular	O
+weight	O
+standards	O
+(	O
+Sigma	O
+)	O
+:	O
+blue	O
+dextran	O
+(	O
+2000	O
+kDa	O
+)	O
+,	O
+thyroglobulin	O
+(	O
+669	O
+kDa	O
+)	O
+,	O
+apoferritin	O
+(	O
+443	O
+kDa	O
+)	O
+,	O
+alcohol	O
+dehydrogenase	O
+(	O
+150	O
+kDa	O
+)	O
+,	O
+and	O
+bovine	B
+serum	O
+albumin	O
+(	O
+66	O
+kDa	O
+)	O
+.	O
+
+Yeast	B
+were	O
+lysed	O
+as	O
+described	O
+for	O
+polyribosome	O
+analysis	O
+,	O
+with	O
+an	O
+additional	O
+clarification	O
+by	O
+passage	O
+through	O
+a	O
+0	O
+.	O
+2	O
+micro	O
+m	O
+syringe	O
+-	O
+tip	O
+filter	O
+(	O
+Acrodisc	O
+)	O
+and	O
+run	O
+over	O
+the	O
+column	O
+at	O
+a	O
+rate	O
+of	O
+0	O
+.	O
+5	O
+ml	O
+/	O
+min	O
+in	O
+polyribosome	O
+lysis	O
+buffer	O
+following	O
+treatment	O
+with	O
+the	O
+indicated	O
+reagents	O
+.	O
+
+Fractions	O
+(	O
+2	O
+.	O
+0	O
+ml	O
+)	O
+were	O
+collected	O
+,	O
+from	O
+which	O
+12	O
+micro	O
+l	O
+were	O
+combined	O
+with	O
+sample	O
+buffer	O
+(	O
+2	O
+%	O
+SDS	O
+,	O
+10	O
+%	O
+glycerol	O
+,	O
+100	O
+mM	O
+dithiothreitol	O
+,	O
+60	O
+mM	O
+Tris	O
+pH	O
+6	O
+.	O
+8	O
+,	O
+0	O
+.	O
+001	O
+%	O
+bromophenol	O
+blue	O
+)	O
+and	O
+analyzed	O
+by	O
+western	O
+blot	O
+using	O
+the	O
+indicated	O
+antibodies	O
+.	O
+
+alpha	O
+-	O
+FLAG	O
+affinity	O
+chromatography	O
+
+For	O
+most	O
+experiments	O
+,	O
+one	O
+liter	O
+yeast	B
+cultures	O
+were	O
+grown	O
+to	O
+early	O
+log	O
+-	O
+phase	O
+and	O
+harvested	O
+by	O
+centrifugation	O
+.	O
+
+Cells	O
+were	O
+washed	O
+twice	O
+in	O
+T75	O
+buffer	O
+(	O
+25	O
+mM	O
+Tris	O
+pH	O
+7	O
+.	O
+5	O
+,	O
+75	O
+mM	O
+NaCl	O
+)	O
+and	O
+then	O
+were	O
+lysed	O
+by	O
+vortex	O
+agitation	O
+with	O
+an	O
+equal	O
+volume	O
+of	O
+glass	O
+beads	O
+in	O
+4	O
+ml	O
+T75	O
+buffer	O
+containing	O
+30	O
+mM	O
+EDTA	O
+.	O
+
+Lysate	O
+was	O
+transferred	O
+to	O
+a	O
+clean	O
+microfuge	O
+tube	O
+,	O
+and	O
+centrifuged	O
+for	O
+10	O
+min	O
+at	O
+3000	O
+g	O
+at	O
+4	O
+degrees	O
+C	O
+.	O
+
+The	O
+supernatant	O
+was	O
+again	O
+transferred	O
+to	O
+a	O
+clean	O
+microfuge	O
+tube	O
+and	O
+centrifuged	O
+at	O
+12	O
+000	O
+g	O
+for	O
+15	O
+min	O
+at	O
+4	O
+degrees	O
+C	O
+,	O
+and	O
+finally	O
+passed	O
+through	O
+a	O
+0	O
+.	O
+2	O
+micro	O
+m	O
+syringe	O
+filter	O
+.	O
+
+Lysate	O
+was	O
+then	O
+pre	O
+-	O
+purified	O
+by	O
+running	O
+over	O
+the	O
+S	O
+-	O
+300	O
+gel	O
+-	O
+filtration	O
+column	O
+in	O
+T75	O
+buffer	O
+,	O
+with	O
+pooling	O
+of	O
+the	O
+void	O
+volume	O
+fractions	O
+(	O
+~	O
+10	O
+ml	O
+total	O
+)	O
+.	O
+
+For	O
+several	O
+experiments	O
+(	O
+Fig	O
+.	O
+5A	O
+,	O
+B	O
+,	O
+E	O
+and	O
+F	O
+)	O
+,	O
+a	O
+low	O
+concentration	O
+(	O
+<	O
+10	O
+micro	O
+g	O
+/	O
+ml	O
+)	O
+of	O
+FLAG	O
+peptide	O
+(	O
+N	O
+-	O
+DYKDDDDK	O
+-	O
+C	O
+)	O
+was	O
+added	O
+to	O
+this	O
+sample	O
+.	O
+
+This	O
+void	O
+material	O
+was	O
+then	O
+loaded	O
+onto	O
+a	O
+1	O
+ml	O
+M2	O
+alpha	O
+-	O
+FLAG	O
+column	O
+(	O
+Sigma	O
+)	O
+;	O
+column	O
+flow	O
+-	O
+through	O
+was	O
+passed	O
+over	O
+the	O
+column	O
+a	O
+second	O
+time	O
+.	O
+
+The	O
+column	O
+was	O
+then	O
+washed	O
+extensively	O
+with	O
+75	O
+ml	O
+T75	O
+buffer	O
+;	O
+material	O
+bound	O
+to	O
+the	O
+column	O
+was	O
+eluted	O
+with	O
+5	O
+ml	O
+T75	O
+containing	O
+184	O
+mg	O
+/	O
+ml	O
+FLAG	O
+peptide	O
+.	O
+
+The	O
+peptide	O
+solution	O
+was	O
+allowed	O
+to	O
+incubate	O
+on	O
+the	O
+column	O
+for	O
+20	O
+min	O
+prior	O
+to	O
+collection	O
+of	O
+the	O
+first	O
+1	O
+ml	O
+fraction	O
+;	O
+subsequent	O
+fractions	O
+were	O
+collected	O
+every	O
+10	O
+min	O
+.	O
+
+Samples	O
+of	O
+crude	O
+material	O
+,	O
+S	O
+-	O
+300	O
+void	O
+,	O
+alpha	O
+-	O
+FLAG	O
+flow	O
+-	O
+through	O
+,	O
+first	O
+and	O
+last	O
+wash	O
+,	O
+and	O
+eluate	O
+fractions	O
+were	O
+analyzed	O
+by	O
+western	O
+blot	O
+using	O
+the	O
+indicated	O
+antibodies	O
+.	O
+
+For	O
+Figure	O
+5A	O
+and	O
+E	O
+,	O
+samples	O
+of	O
+first	O
+and	O
+last	O
+wash	O
+and	O
+eluate	O
+fractions	O
+were	O
+concentrated	O
+,	O
+run	O
+on	O
+SDS	O
+-	O
+PAGE	O
+and	O
+stained	O
+with	O
+colloidal	O
+G250	O
+Coomassie	O
+.	O
+
+Concentration	O
+of	O
+samples	O
+
+Where	O
+indicated	O
+,	O
+samples	O
+were	O
+concentrated	O
+using	O
+the	O
+method	O
+of	O
+Traub	O
+et	O
+al	O
+.	O
+
+(	O
+21	O
+)	O
+.	O
+
+400	O
+micro	O
+l	O
+of	O
+sample	O
+were	O
+transferred	O
+to	O
+a	O
+microfuge	O
+tube	O
+,	O
+and	O
+combined	O
+with	O
+400	O
+micro	O
+l	O
+of	O
+methanol	O
+,	O
+and	O
+100	O
+micro	O
+l	O
+of	O
+chloroform	O
+.	O
+
+Samples	O
+were	O
+then	O
+vortexed	O
+vigorously	O
+,	O
+and	O
+centrifuged	O
+for	O
+5	O
+min	O
+at	O
+12	O
+000	O
+g	O
+.	O
+
+The	O
+supernatant	O
+was	O
+discarded	O
+,	O
+leaving	O
+the	O
+interface	O
+intact	O
+,	O
+and	O
+an	O
+additional	O
+400	O
+micro	O
+l	O
+of	O
+methanol	O
+was	O
+added	O
+to	O
+each	O
+tube	O
+.	O
+
+Samples	O
+were	O
+then	O
+inverted	O
+several	O
+times	O
+,	O
+and	O
+centrifuged	O
+again	O
+for	O
+5	O
+min	O
+.	O
+
+The	O
+supernatant	O
+was	O
+discarded	O
+,	O
+and	O
+the	O
+protein	O
+pellet	O
+was	O
+air	O
+-	O
+dried	O
+and	O
+resuspended	O
+in	O
+1	O
+x	O
+sample	O
+buffer	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+
+Western	O
+blot	O
+analysis	O
+was	O
+performed	O
+essentially	O
+as	O
+described	O
+previously	O
+(	O
+19	O
+)	O
+.	O
+
+Briefly	O
+,	O
+samples	O
+to	O
+be	O
+analyzed	O
+were	O
+mixed	O
+with	O
+sample	O
+buffer	O
+,	O
+boiled	O
+,	O
+electrophoresed	O
+through	O
+a	O
+10	O
+%	O
+SDS	O
+-	O
+polyacrylamide	O
+gel	O
+,	O
+and	O
+electro	O
+-	O
+blotted	O
+onto	O
+nitrocellulose	O
+(	O
+Bio	O
+-	O
+Rad	O
+)	O
+.	O
+
+FLAG	O
+-	O
+Scp160p	O
+fusion	O
+protein	O
+was	O
+detected	O
+by	O
+incubation	O
+of	O
+the	O
+filter	O
+with	O
+mouse	B
+M2	O
+anti	O
+-	O
+FLAG	O
+monoclonal	O
+antibody	O
+(	O
+10	O
+micro	O
+g	O
+/	O
+ml	O
+final	O
+concentration	O
+)	O
+,	O
+followed	O
+by	O
+HRP	O
+-	O
+conjugated	O
+sheep	B
+anti	O
+-	O
+mouse	B
+secondary	O
+antibody	O
+(	O
+Amersham	O
+)	O
+,	O
+diluted	O
+1	O
+:	O
+5000	O
+as	O
+per	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+,	O
+and	O
+ECL	O
+reagent	O
+(	O
+Amersham	O
+)	O
+,	O
+followed	O
+by	O
+exposure	O
+to	O
+X	O
+-	O
+ray	O
+film	O
+.	O
+
+HA	O
+-	O
+tagged	O
+Scp160p	O
+and	O
+HA	O
+-	O
+tagged	O
+Bfr1p	O
+were	O
+detected	O
+using	O
+the	O
+12CA5	O
+mAb	O
+(	O
+Boehringer	O
+Mannheim	O
+)	O
+at	O
+a	O
+final	O
+concentration	O
+of	O
+0	O
+.	O
+8	O
+micro	O
+g	O
+/	O
+ml	O
+;	O
+Pab1p	O
+and	O
+Pub1p	O
+were	O
+detected	O
+using	O
+1G1	O
+mAb	O
+at	O
+1	O
+:	O
+5000	O
+,	O
+and	O
+4C3	O
+mAb	O
+at	O
+1	O
+:	O
+1000	O
+,	O
+respectively	O
+,	O
+both	O
+generous	O
+gifts	O
+from	O
+Dr	O
+Maurice	O
+Swanson	O
+(	O
+22	O
+,	O
+23	O
+)	O
+.	O
+
+Where	O
+appropriate	O
+,	O
+films	O
+were	O
+analyzed	O
+by	O
+scanning	O
+densitometry	O
+(	O
+Molecular	O
+Dynamics	O
+)	O
+,	O
+and	O
+quantitated	O
+using	O
+ImageQuant	O
+software	O
+(	O
+Molecular	O
+Dynamics	O
+)	O
+.	O
+
+Colloidal	O
+G250	O
+coomassie	O
+staining	O
+
+Procedure	O
+used	O
+was	O
+that	O
+of	O
+Neuhoff	O
+(	O
+24	O
+)	O
+.	O
+
+Briefly	O
+,	O
+a	O
+one	O
+liter	O
+stock	O
+of	O
+staining	O
+solution	O
+was	O
+prepared	O
+containing	O
+1	O
+g	O
+Coomassie	O
+brilliant	O
+blue	O
+G	O
+-	O
+250	O
+(	O
+Sigma	O
+)	O
+,	O
+100	O
+g	O
+ammonium	O
+sulfate	O
+(	O
+Sigma	O
+)	O
+,	O
+and	O
+11	O
+.	O
+76	O
+ml	O
+85	O
+%	O
+phosphoric	O
+acid	O
+(	O
+Fisher	O
+)	O
+.	O
+
+Following	O
+SDS	O
+-	O
+PAGE	O
+,	O
+gels	O
+were	O
+fixed	O
+in	O
+40	O
+%	O
+methanol	O
+,	O
+10	O
+%	O
+acetic	O
+acid	O
+for	O
+10	O
+min	O
+.	O
+
+Gels	O
+were	O
+then	O
+rinsed	O
+several	O
+times	O
+in	O
+water	O
+,	O
+then	O
+stained	O
+using	O
+40	O
+ml	O
+of	O
+the	O
+stock	O
+staining	O
+solution	O
+mixed	O
+with	O
+10	O
+ml	O
+methanol	O
+,	O
+for	O
+2	O
+h	O
+at	O
+room	O
+temperature	O
+.	O
+
+Stain	O
+was	O
+then	O
+poured	O
+off	O
+,	O
+and	O
+residual	O
+stain	O
+was	O
+removed	O
+by	O
+rinsing	O
+in	O
+water	O
+.	O
+
+By	O
+performing	O
+a	O
+standard	O
+analysis	O
+using	O
+bovine	B
+serum	O
+albumin	O
+,	O
+the	O
+stain	O
+was	O
+able	O
+to	O
+detect	O
+~	O
+15	O
+ng	O
+total	O
+protein	O
+per	O
+lane	O
+.	O
+
+Pichia	O
+expression	O
+system	O
+
+An	O
+N	O
+-	O
+terminally	O
+HIS6	O
+/	O
+FLAG	O
+-	O
+tagged	O
+allele	O
+of	O
+the	O
+SCP160	O
+coding	O
+sequence	O
+was	O
+blunt	O
+-	O
+end	O
+sub	O
+-	O
+cloned	O
+into	O
+the	O
+BamHI	O
+/	O
+SnaBI	O
+sites	O
+of	O
+the	O
+Pichia	O
+expression	O
+vector	O
+pPIC3	O
+.	O
+5K	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+The	O
+construct	O
+was	O
+then	O
+linearized	O
+using	O
+SalI	O
+and	O
+integrated	O
+into	O
+the	O
+genome	O
+of	O
+the	O
+Pichia	O
+strain	O
+GS115	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+High	O
+expression	O
+transformants	O
+were	O
+selected	O
+initially	O
+on	O
+histidine	O
+-	O
+deficient	O
+medium	O
+followed	O
+by	O
+selection	O
+on	O
+increasing	O
+concentrations	O
+of	O
+G418	O
+(	O
+US	O
+Biological	O
+)	O
+.	O
+
+Crude	O
+lysates	O
+of	O
+the	O
+resultant	O
+transformants	O
+were	O
+then	O
+confirmed	O
+by	O
+western	O
+blot	O
+analysis	O
+with	O
+the	O
+anti	O
+-	O
+FLAG	O
+antibody	O
+M2	O
+,	O
+and	O
+the	O
+best	O
+expressing	O
+strain	O
+was	O
+cultured	O
+in	O
+a	O
+fermenter	O
+,	O
+harvested	O
+,	O
+and	O
+lysed	O
+by	O
+agitation	O
+with	O
+glass	O
+beads	O
+.	O
+
+To	O
+purify	O
+Scp160p	O
+,	O
+2	O
+ml	O
+of	O
+crude	O
+lysate	O
+was	O
+first	O
+diluted	O
+to	O
+10	O
+ml	O
+with	O
+25	O
+mM	O
+Tris	O
+,	O
+pH	O
+7	O
+.	O
+5	O
+,	O
+1	O
+M	O
+NaCl	O
+,	O
+then	O
+twice	O
+passed	O
+over	O
+a	O
+1	O
+ml	O
+alpha	O
+-	O
+FLAG	O
+affinity	O
+column	O
+.	O
+
+The	O
+column	O
+was	O
+then	O
+washed	O
+with	O
+75	O
+ml	O
+of	O
+25	O
+mM	O
+Tris	O
+,	O
+pH	O
+7	O
+.	O
+5	O
+,	O
+1	O
+M	O
+NaCl	O
+,	O
+and	O
+then	O
+eluted	O
+with	O
+184	O
+micro	O
+g	O
+/	O
+ml	O
+FLAG	O
+peptide	O
+prepared	O
+in	O
+the	O
+same	O
+buffer	O
+.	O
+
+RESULTS	O
+
+Expression	O
+of	O
+tagged	O
+Scp160p	O
+in	O
+yeast	B
+
+An	O
+N	O
+-	O
+terminal	O
+FLAG	O
+-	O
+tagged	O
+form	O
+of	O
+Scp160p	O
+was	O
+created	O
+to	O
+facilitate	O
+detection	O
+of	O
+the	O
+protein	O
+in	O
+cells	O
+and	O
+extracts	O
+(	O
+Fig	O
+.	O
+1A	O
+)	O
+.	O
+
+To	O
+probe	O
+functionality	O
+of	O
+this	O
+fusion	O
+protein	O
+,	O
+we	O
+used	O
+two	O
+-	O
+step	O
+gene	O
+replacement	O
+(	O
+18	O
+)	O
+to	O
+substitute	O
+the	O
+modified	O
+allele	O
+into	O
+the	O
+SCP160	O
+locus	O
+of	O
+haploid	O
+yeast	B
+,	O
+and	O
+then	O
+tested	O
+the	O
+morphological	O
+phenotype	O
+of	O
+the	O
+resultant	O
+cells	O
+.	O
+
+All	O
+strains	O
+were	O
+confirmed	O
+by	O
+PCR	O
+analysis	O
+of	O
+the	O
+SCP160	O
+locus	O
+with	O
+appropriate	O
+primers	O
+(	O
+Materials	O
+and	O
+Methods	O
+)	O
+,	O
+and	O
+expression	O
+of	O
+the	O
+tagged	O
+protein	O
+was	O
+confirmed	O
+by	O
+western	O
+blot	O
+analysis	O
+with	O
+the	O
+appropriate	O
+antibody	O
+(	O
+M2	O
+alpha	O
+FLAG	O
+)	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+In	O
+all	O
+cases	O
+,	O
+yeast	B
+expressing	O
+tagged	O
+Scp160p	O
+in	O
+place	O
+of	O
+the	O
+native	O
+protein	O
+appeared	O
+indistinguishable	O
+from	O
+the	O
+corresponding	O
+wild	O
+-	O
+type	O
+strains	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+As	O
+a	O
+negative	O
+control	O
+,	O
+we	O
+also	O
+deleted	O
+almost	O
+the	O
+entire	O
+SCP160	O
+coding	O
+region	O
+from	O
+the	O
+genomes	O
+of	O
+these	O
+yeast	B
+strains	O
+(	O
+Fig	O
+.	O
+1A	O
+)	O
+,	O
+and	O
+confirmed	O
+the	O
+expected	O
+mutant	O
+phenotype	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Scp160p	O
+associates	O
+with	O
+polyribosomes	O
+
+To	O
+test	O
+the	O
+hypothesis	O
+that	O
+Scp160p	O
+associates	O
+with	O
+polyribosomes	O
+we	O
+used	O
+sucrose	O
+gradient	O
+ultracentrifugation	O
+to	O
+size	O
+-	O
+fractionate	O
+subcellular	O
+components	O
+of	O
+lysates	O
+prepared	O
+from	O
+yeast	B
+expressing	O
+the	O
+N	O
+-	O
+terminal	O
+FLAG	O
+-	O
+tagged	O
+Scp160p	O
+protein	O
+.	O
+
+Western	O
+blot	O
+analyses	O
+of	O
+gradient	O
+fractions	O
+with	O
+an	O
+alpha	O
+-	O
+FLAG	O
+antibody	O
+(	O
+M2	O
+,	O
+Boehringer	O
+Mannheim	O
+)	O
+,	O
+revealed	O
+a	O
+160	O
+kDa	O
+band	O
+that	O
+was	O
+most	O
+abundant	O
+in	O
+the	O
+denser	O
+fractions	O
+,	O
+consistent	O
+with	O
+the	O
+location	O
+of	O
+polyribosomes	O
+(	O
+>	O
+80S	O
+)	O
+(	O
+Fig	O
+.	O
+2A	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+A	O
+convenient	O
+internal	O
+control	O
+for	O
+these	O
+gradients	O
+was	O
+provided	O
+by	O
+an	O
+unknown	O
+endogenous	O
+yeast	B
+cross	O
+-	O
+reacting	O
+protein	O
+at	O
+~	O
+100	O
+kDa	O
+,	O
+that	O
+exemplified	O
+the	O
+migration	O
+pattern	O
+of	O
+a	O
+free	O
+protein	O
+,	O
+appearing	O
+only	O
+in	O
+the	O
+upper	O
+fractions	O
+of	O
+the	O
+gradient	O
+(	O
+Fig	O
+.	O
+2A	O
+,	O
+open	O
+arrow	O
+)	O
+.	O
+
+To	O
+determine	O
+whether	O
+the	O
+migration	O
+pattern	O
+of	O
+Scp160p	O
+in	O
+these	O
+sucrose	O
+gradients	O
+truly	O
+reflected	O
+association	O
+with	O
+yeast	B
+polyribosomes	O
+,	O
+lysates	O
+were	O
+pre	O
+-	O
+treated	O
+with	O
+either	O
+30	O
+mM	O
+EDTA	O
+or	O
+50	O
+U	O
+/	O
+ml	O
+RNase	O
+One	O
+(	O
+Promega	O
+)	O
+immediately	O
+prior	O
+to	O
+sucrose	O
+gradient	O
+fractionation	O
+.	O
+
+EDTA	O
+chelates	O
+Mg2	O
++	O
+cations	O
+,	O
+resulting	O
+in	O
+the	O
+dissociation	O
+of	O
+the	O
+small	O
+and	O
+large	O
+ribosomal	O
+subunits	O
+,	O
+reflected	O
+in	O
+gradient	O
+profiles	O
+(	O
+OD254	O
+)	O
+by	O
+the	O
+disappearance	O
+of	O
+80S	O
+monosomes	O
+and	O
+polyribosomes	O
+along	O
+with	O
+a	O
+marked	O
+increase	O
+in	O
+the	O
+abundance	O
+of	O
+free	O
+ribosomal	O
+subunits	O
+(	O
+Fig	O
+.	O
+2B	O
+)	O
+.	O
+
+Under	O
+these	O
+conditions	O
+,	O
+the	O
+greatest	O
+intensity	O
+of	O
+FLAG	O
+-	O
+Scp160p	O
+signal	O
+was	O
+seen	O
+only	O
+in	O
+the	O
+upper	O
+-	O
+most	O
+fractions	O
+of	O
+the	O
+gradient	O
+(	O
+Fig	O
+.	O
+2B	O
+)	O
+.	O
+
+Alternatively	O
+,	O
+pre	O
+-	O
+treatment	O
+of	O
+lysates	O
+with	O
+RNase	O
+,	O
+which	O
+results	O
+in	O
+inter	O
+-	O
+ribosomal	O
+severing	O
+of	O
+translating	O
+messages	O
+,	O
+gave	O
+rise	O
+to	O
+a	O
+large	O
+pool	O
+of	O
+single	O
+80S	O
+ribosomes	O
+(	O
+Fig	O
+.	O
+2C	O
+)	O
+.	O
+
+Again	O
+,	O
+FLAG	O
+-	O
+Scp160p	O
+was	O
+shifted	O
+to	O
+the	O
+uppermost	O
+fractions	O
+of	O
+these	O
+gradients	O
+.	O
+
+Although	O
+some	O
+of	O
+the	O
+Scp160p	O
+signal	O
+was	O
+detected	O
+in	O
+fractions	O
+larger	O
+than	O
+40S	O
+,	O
+the	O
+migration	O
+pattern	O
+of	O
+the	O
+100	O
+kDa	O
+cross	O
+-	O
+reacting	O
+protein	O
+in	O
+these	O
+experiments	O
+indicated	O
+that	O
+RNase	O
+treatment	O
+caused	O
+an	O
+apparent	O
+diffusion	O
+of	O
+material	O
+in	O
+the	O
+upper	O
+portion	O
+of	O
+the	O
+gradient	O
+.	O
+
+Characterization	O
+of	O
+Scp160p	O
+-	O
+containing	O
+complexes	O
+following	O
+EDTA	O
+and	O
+RNase	O
+treatment	O
+
+Gel	O
+-	O
+filtration	O
+chromatography	O
+was	O
+used	O
+to	O
+determine	O
+the	O
+apparent	O
+molecular	O
+weight	O
+of	O
+Scp160p	O
+following	O
+its	O
+release	O
+from	O
+polyribosomes	O
+by	O
+both	O
+EDTA	O
+and	O
+RNase	O
+treatment	O
+.	O
+
+Lysates	O
+were	O
+prepared	O
+as	O
+described	O
+above	O
+for	O
+sucrose	O
+gradient	O
+analysis	O
+,	O
+but	O
+were	O
+instead	O
+size	O
+fractionated	O
+over	O
+a	O
+Sephacryl	O
+S	O
+-	O
+300	O
+Hi	O
+-	O
+Prep	O
+column	O
+,	O
+with	O
+an	O
+inclusion	O
+cut	O
+-	O
+off	O
+of	O
+1300	O
+kDa	O
+.	O
+
+As	O
+expected	O
+,	O
+Scp160p	O
+from	O
+untreated	O
+lysates	O
+eluted	O
+in	O
+the	O
+void	O
+volume	O
+,	O
+confirming	O
+its	O
+association	O
+with	O
+large	O
+complexes	O
+,	O
+ostensibly	O
+polyribosomes	O
+(	O
+Fig	O
+.	O
+3A	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+In	O
+EDTA	O
+treated	O
+lysates	O
+,	O
+all	O
+Scp160p	O
+signal	O
+was	O
+still	O
+detected	O
+in	O
+the	O
+void	O
+volume	O
+,	O
+indicating	O
+it	O
+remained	O
+in	O
+a	O
+complex	O
+of	O
+>	O
+1300	O
+kDa	O
+(	O
+Fig	O
+.	O
+3B	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+limited	O
+RNase	O
+treatment	O
+(	O
+10	O
+min	O
+)	O
+resulted	O
+in	O
+the	O
+appearance	O
+of	O
+an	O
+Scp160p	O
+-	O
+containing	O
+species	O
+of	O
+~	O
+450	O
+kDa	O
+,	O
+in	O
+addition	O
+to	O
+a	O
+fraction	O
+still	O
+visible	O
+in	O
+the	O
+void	O
+(	O
+Fig	O
+.	O
+3C	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+More	O
+extensive	O
+RNase	O
+treatment	O
+(	O
+30	O
+min	O
+)	O
+led	O
+to	O
+complete	O
+conversion	O
+to	O
+the	O
+450	O
+kDa	O
+species	O
+(	O
+Fig	O
+.	O
+3D	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+Sequential	O
+treatment	O
+,	O
+first	O
+with	O
+RNase	O
+,	O
+then	O
+with	O
+EDTA	O
+,	O
+also	O
+resulted	O
+in	O
+a	O
+450	O
+kDa	O
+species	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+suggesting	O
+that	O
+all	O
+components	O
+of	O
+this	O
+apparent	O
+450	O
+kDa	O
+complex	O
+were	O
+also	O
+present	O
+following	O
+EDTA	O
+treatment	O
+alone	O
+.	O
+
+As	O
+before	O
+,	O
+the	O
+100	O
+kDa	O
+,	O
+endogenous	O
+alpha	O
+-	O
+FLAG	O
+cross	O
+-	O
+reacting	O
+protein	O
+(	O
+Fig	O
+.	O
+3	O
+,	O
+open	O
+arrows	O
+)	O
+served	O
+as	O
+a	O
+convenient	O
+internal	O
+control	O
+,	O
+eluting	O
+from	O
+the	O
+column	O
+at	O
+a	O
+volume	O
+consistent	O
+with	O
+its	O
+expected	O
+monomeric	O
+size	O
+.	O
+
+To	O
+characterize	O
+further	O
+the	O
+stability	O
+of	O
+the	O
+large	O
+(	O
+apparent	O
+molecular	O
+weight	O
+>	O
+1300	O
+kDa	O
+)	O
+,	O
+EDTA	O
+-	O
+resistant	O
+complex	O
+,	O
+lysates	O
+were	O
+treated	O
+with	O
+increasing	O
+concentrations	O
+of	O
+NaCl	O
+prior	O
+to	O
+size	O
+fractionation	O
+(	O
+Fig	O
+.	O
+3	O
+,	O
+panels	O
+E	O
+,	O
+F	O
+and	O
+G	O
+)	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+3E	O
+,	O
+at	O
+75	O
+mM	O
+NaCl	O
+,	O
+the	O
+large	O
+complex	O
+remained	O
+intact	O
+.	O
+
+However	O
+,	O
+at	O
+a	O
+NaCl	O
+concentration	O
+of	O
+150	O
+mM	O
+,	O
+the	O
+Scp160p	O
+complex	O
+was	O
+partially	O
+reduced	O
+to	O
+450	O
+kDa	O
+,	O
+with	O
+some	O
+signal	O
+still	O
+remaining	O
+in	O
+the	O
+void	O
+(	O
+Fig	O
+.	O
+3F	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+Following	O
+treatment	O
+with	O
+1	O
+M	O
+NaCl	O
+,	O
+Scp160p	O
+was	O
+only	O
+visible	O
+as	O
+the	O
+450	O
+kDa	O
+species	O
+(	O
+Fig	O
+.	O
+3G	O
+,	O
+solid	O
+arrow	O
+)	O
+.	O
+
+The	O
+fact	O
+that	O
+RNase	O
+treatment	O
+and	O
+high	O
+salt	O
+both	O
+generated	O
+Scp160p	O
+species	O
+of	O
+similar	O
+apparent	O
+molecular	O
+weight	O
+suggests	O
+that	O
+these	O
+high	O
+salt	O
+concentrations	O
+resulted	O
+in	O
+the	O
+disassociation	O
+of	O
+RNA	O
+,	O
+and	O
+perhaps	O
+other	O
+components	O
+,	O
+from	O
+Scp160p	O
+.	O
+
+Pab1p	O
+and	O
+Bfr1p	O
+are	O
+present	O
+in	O
+EDTA	O
+-	O
+resistant	O
+Scp160p	O
+-	O
+containing	O
+complexes	O
+
+To	O
+determine	O
+if	O
+the	O
+>	O
+1300	O
+kDa	O
+Scp160p	O
+-	O
+containing	O
+complexes	O
+remaining	O
+after	O
+EDTA	O
+treatment	O
+were	O
+mRNPs	O
+,	O
+we	O
+assayed	O
+for	O
+the	O
+presence	O
+of	O
+the	O
+yeast	B
+poly	O
+(	O
+A	O
+)	O
+binding	O
+protein	O
+,	O
+Pab1p	O
+,	O
+following	O
+alpha	O
+-	O
+FLAG	O
+affinity	O
+purification	O
+as	O
+illustrated	O
+in	O
+Figure	O
+4	O
+.	O
+
+Pab1p	O
+is	O
+an	O
+abundant	O
+and	O
+well	O
+-	O
+characterized	O
+component	O
+of	O
+mRNP	O
+complexes	O
+in	O
+yeast	B
+,	O
+as	O
+well	O
+as	O
+higher	O
+eukaryotes	O
+(	O
+14	O
+,	O
+15	O
+,	O
+25	O
+)	O
+.	O
+
+As	O
+seen	O
+in	O
+Figure	O
+5A	O
+and	O
+B	O
+,	O
+Pab1p	O
+did	O
+co	O
+-	O
+purify	O
+with	O
+FLAG	O
+-	O
+Scp160p	O
+;	O
+moreover	O
+,	O
+treatment	O
+with	O
+RNase	O
+immediately	O
+prior	O
+to	O
+FLAG	O
+-	O
+purification	O
+completely	O
+abolished	O
+this	O
+interaction	O
+(	O
+Fig	O
+.	O
+5C	O
+)	O
+,	O
+indicating	O
+an	O
+RNA	O
+-	O
+dependant	O
+association	O
+between	O
+these	O
+two	O
+proteins	O
+.	O
+
+We	O
+also	O
+probed	O
+the	O
+isolated	O
+complexes	O
+for	O
+the	O
+presence	O
+of	O
+another	O
+abundant	O
+mRNP	O
+-	O
+component	O
+protein	O
+,	O
+Pub1p	O
+(	O
+23	O
+,	O
+26	O
+)	O
+.	O
+
+Pub1p	O
+,	O
+as	O
+opposed	O
+to	O
+Pab1p	O
+,	O
+is	O
+not	O
+reported	O
+to	O
+associate	O
+with	O
+polyribosomes	O
+,	O
+and	O
+is	O
+hypothesized	O
+to	O
+bind	O
+a	O
+pool	O
+of	O
+non	O
+-	O
+translatable	O
+mRNAs	O
+(	O
+23	O
+)	O
+.	O
+
+As	O
+predicted	O
+,	O
+Pub1p	O
+did	O
+not	O
+co	O
+-	O
+purify	O
+with	O
+Scp160p	O
+(	O
+Fig	O
+.	O
+5D	O
+)	O
+.	O
+
+The	O
+absence	O
+of	O
+Pub1p	O
+in	O
+Scp160p	O
+-	O
+containing	O
+complexes	O
+served	O
+as	O
+a	O
+negative	O
+control	O
+,	O
+demonstrating	O
+that	O
+abundant	O
+RNA	O
+-	O
+binding	O
+proteins	O
+did	O
+not	O
+co	O
+-	O
+purify	O
+non	O
+-	O
+specifically	O
+by	O
+this	O
+protocol	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+performed	O
+mock	O
+purifications	O
+using	O
+lysates	O
+from	O
+yeast	B
+expressing	O
+the	O
+wild	O
+-	O
+type	O
+allele	O
+of	O
+SCP160	O
+without	O
+the	O
+FLAG	O
+epitope	O
+(	O
+Fig	O
+.	O
+5F	O
+)	O
+,	O
+or	O
+with	O
+an	O
+unrelated	O
+FLAG	O
+-	O
+tagged	O
+protein	O
+,	O
+human	B
+galactose	O
+1	O
+-	O
+phosphate	O
+uridylyltransferase	O
+(	O
+GALT	O
+)	O
+(	O
+Fig	O
+.	O
+5G	O
+,	O
+lower	O
+panel	O
+)	O
+.	O
+
+In	O
+neither	O
+case	O
+did	O
+Pab1p	O
+bind	O
+and	O
+elute	O
+from	O
+the	O
+FLAG	O
+affinity	O
+column	O
+.	O
+
+Finally	O
+,	O
+no	O
+bands	O
+were	O
+visible	O
+by	O
+colloidal	O
+G250	O
+Coomassie	O
+staining	O
+of	O
+samples	O
+from	O
+the	O
+mock	O
+(	O
+wild	O
+-	O
+type	O
+)	O
+preparations	O
+(	O
+Fig	O
+.	O
+5E	O
+)	O
+,	O
+further	O
+demonstrating	O
+the	O
+specificity	O
+of	O
+this	O
+procedure	O
+.	O
+
+By	O
+colloidal	O
+G250	O
+Coomassie	O
+staining	O
+(	O
+Materials	O
+and	O
+Methods	O
+)	O
+of	O
+the	O
+FLAG	O
+-	O
+purified	O
+complex	O
+,	O
+we	O
+observed	O
+in	O
+addition	O
+to	O
+Scp160p	O
+,	O
+two	O
+major	O
+bands	O
+,	O
+at	O
+~	O
+70	O
+kDa	O
+and	O
+~	O
+55	O
+kDa	O
+,	O
+which	O
+ostensibly	O
+represent	O
+co	O
+-	O
+purifying	O
+proteins	O
+(	O
+Fig	O
+.	O
+5A	O
+,	O
+bottom	O
+panel	O
+)	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+suggested	O
+that	O
+the	O
+~	O
+70	O
+kDa	O
+species	O
+is	O
+Pab1p	O
+.	O
+
+To	O
+identify	O
+the	O
+55	O
+kDa	O
+protein	O
+,	O
+that	O
+band	O
+was	O
+excised	O
+from	O
+the	O
+gel	O
+,	O
+and	O
+sent	O
+to	O
+the	O
+Keck	O
+microchemical	O
+facility	O
+at	O
+Yale	O
+University	O
+for	O
+analysis	O
+by	O
+in	O
+gel	O
+tryptic	O
+digestion	O
+,	O
+followed	O
+by	O
+MALDI	O
+-	O
+mass	O
+spectrometry	O
+.	O
+
+The	O
+results	O
+of	O
+these	O
+analyses	O
+clearly	O
+identified	O
+the	O
+unknown	O
+protein	O
+as	O
+Bfr1p	O
+.	O
+
+To	O
+confirm	O
+this	O
+result	O
+,	O
+an	O
+N	O
+-	O
+terminal	O
+HA	O
+tag	O
+was	O
+engineered	O
+onto	O
+the	O
+genomic	O
+BFR1	O
+locus	O
+in	O
+strains	O
+expressing	O
+FLAG	O
+-	O
+tagged	O
+or	O
+wild	O
+-	O
+type	O
+Scp160p	O
+.	O
+
+Scp160p	O
+complexes	O
+were	O
+then	O
+isolated	O
+from	O
+both	O
+of	O
+these	O
+strains	O
+using	O
+the	O
+protocol	O
+described	O
+above	O
+.	O
+
+As	O
+seen	O
+in	O
+Figure	O
+6	O
+,	O
+an	O
+HA	O
+-	O
+tagged	O
+protein	O
+of	O
+~	O
+55	O
+kDa	O
+(	O
+center	O
+panel	O
+)	O
+appears	O
+in	O
+alpha	O
+-	O
+FLAG	O
+column	O
+elutions	O
+only	O
+when	O
+FLAG	O
+-	O
+Scp160p	O
+is	O
+also	O
+present	O
+(	O
+top	O
+panel	O
+)	O
+.	O
+
+No	O
+signal	O
+is	O
+visible	O
+in	O
+mock	O
+purifications	O
+of	O
+extracts	O
+where	O
+Scp160p	O
+is	O
+not	O
+FLAG	O
+-	O
+tagged	O
+(	O
+bottom	O
+panel	O
+)	O
+.	O
+
+Monomeric	O
+Scp160p	O
+migrates	O
+as	O
+a	O
+~	O
+450	O
+kDa	O
+protein	O
+under	O
+native	O
+conditions	O
+
+As	O
+a	O
+first	O
+step	O
+to	O
+characterize	O
+the	O
+post	O
+RNase	O
+/	O
+NaCl	O
+450	O
+kDa	O
+Scp160p	O
+species	O
+we	O
+compared	O
+it	O
+with	O
+Scp160p	O
+over	O
+-	O
+expressed	O
+and	O
+purified	O
+from	O
+an	O
+exogenous	O
+host	O
+,	O
+the	O
+yeast	B
+Pichia	B
+pastoris	I
+.	O
+
+The	O
+purified	O
+N	O
+-	O
+terminal	O
+FLAG	O
+/	O
+hexahistidine	O
+-	O
+tagged	O
+Scp160p	O
+was	O
+run	O
+over	O
+an	O
+S300	O
+gel	O
+filtration	O
+column	O
+;	O
+2	O
+ml	O
+fractions	O
+were	O
+collected	O
+and	O
+analyzed	O
+by	O
+alpha	O
+-	O
+FLAG	O
+western	O
+blot	O
+.	O
+
+As	O
+seen	O
+in	O
+Figure	O
+7A	O
+,	O
+purified	O
+Scp160p	O
+eluted	O
+at	O
+a	O
+volume	O
+consistent	O
+with	O
+a	O
+>	O
+443	O
+kDa	O
+protein	O
+.	O
+
+To	O
+confirm	O
+that	O
+no	O
+other	O
+proteins	O
+were	O
+associated	O
+with	O
+the	O
+purified	O
+Scp160p	O
+,	O
+12	O
+micro	O
+l	O
+of	O
+the	O
+protein	O
+was	O
+run	O
+on	O
+SDS	O
+-	O
+PAGE	O
+and	O
+subjected	O
+to	O
+colloidal	O
+G250	O
+Coomassie	O
+staining	O
+before	O
+loading	O
+on	O
+the	O
+S	O
+-	O
+300	O
+column	O
+(	O
+Fig	O
+.	O
+7B	O
+)	O
+.	O
+
+As	O
+shown	O
+,	O
+no	O
+bands	O
+other	O
+than	O
+Scp160p	O
+were	O
+visible	O
+.	O
+
+Several	O
+KH	O
+-	O
+domain	O
+proteins	O
+,	O
+including	O
+Sam68	O
+and	O
+FMRP	O
+,	O
+have	O
+been	O
+reported	O
+to	O
+form	O
+homodimers	O
+in	O
+vivo	O
+(	O
+27	O
+)	O
+.	O
+
+Therefore	O
+,	O
+we	O
+explored	O
+the	O
+possibility	O
+that	O
+the	O
+~	O
+450	O
+kDa	O
+Scp160p	O
+species	O
+might	O
+contain	O
+two	O
+or	O
+more	O
+copies	O
+of	O
+Scp160p	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+yeast	B
+expressing	O
+FLAG	O
+-	O
+Scp160p	O
+were	O
+transfected	O
+with	O
+a	O
+centromeric	O
+plasmid	O
+,	O
+YCplac22	O
+-	O
+HA	O
+-	O
+Scp160p	O
+,	O
+encoding	O
+a	O
+distinct	O
+,	O
+HA	O
+-	O
+tagged	O
+allele	O
+of	O
+the	O
+protein	O
+.	O
+
+The	O
+functionality	O
+of	O
+this	O
+tagged	O
+protein	O
+had	O
+previously	O
+been	O
+demonstrated	O
+by	O
+polyribosome	O
+association	O
+as	O
+well	O
+as	O
+complementation	O
+of	O
+the	O
+null	O
+morphological	O
+phenotype	O
+in	O
+cells	O
+expressing	O
+only	O
+HA	O
+-	O
+Scp160p	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+As	O
+seen	O
+in	O
+Figure	O
+7C	O
+,	O
+when	O
+yeast	B
+co	O
+-	O
+expressing	O
+the	O
+two	O
+alleles	O
+were	O
+lysed	O
+and	O
+the	O
+FLAG	O
+-	O
+tagged	O
+protein	O
+was	O
+isolated	O
+as	O
+described	O
+above	O
+,	O
+no	O
+HA	O
+-	O
+Scp160p	O
+co	O
+-	O
+purified	O
+with	O
+the	O
+FLAG	O
+-	O
+Scp160p	O
+.	O
+
+These	O
+data	O
+strongly	O
+suggest	O
+that	O
+Scp160p	O
+does	O
+not	O
+form	O
+homo	O
+-	O
+dimers	O
+or	O
+higher	O
+-	O
+order	O
+multimers	O
+in	O
+vivo	O
+,	O
+and	O
+that	O
+the	O
+~	O
+450	O
+kDa	O
+species	O
+of	O
+Scp160p	O
+observed	O
+is	O
+simply	O
+the	O
+monomeric	O
+protein	O
+.	O
+
+DISCUSSION	O
+
+The	O
+data	O
+presented	O
+here	O
+demonstrate	O
+two	O
+main	O
+points	O
+regarding	O
+the	O
+biochemical	O
+associations	O
+and	O
+function	O
+of	O
+Scp160p	O
+in	O
+yeast	B
+.	O
+
+First	O
+,	O
+the	O
+sucrose	O
+gradient	O
+fractionation	O
+data	O
+clearly	O
+demonstrate	O
+that	O
+Scp160p	O
+exists	O
+primarily	O
+associated	O
+with	O
+large	O
+complexes	O
+,	O
+likely	O
+to	O
+be	O
+polyribosomes	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+time	O
+a	O
+vigilin	O
+family	O
+member	O
+has	O
+been	O
+shown	O
+to	O
+associate	O
+with	O
+polyribosomes	O
+in	O
+this	O
+manner	O
+.	O
+
+Interestingly	O
+,	O
+Weber	O
+and	O
+colleagues	O
+did	O
+not	O
+observe	O
+sucrose	O
+gradient	O
+fractionation	O
+data	O
+consistent	O
+with	O
+polyribosome	O
+association	O
+of	O
+Scp160p	O
+(	O
+5	O
+)	O
+.	O
+
+These	O
+authors	O
+hypothesized	O
+that	O
+Scp160p	O
+associates	O
+only	O
+with	O
+membrane	O
+-	O
+bound	O
+polyribosomes	O
+,	O
+and	O
+that	O
+Scp160p	O
+is	O
+not	O
+found	O
+complexed	O
+with	O
+cytosolic	O
+polyribosomes	O
+(	O
+5	O
+)	O
+.	O
+
+Our	O
+data	O
+do	O
+not	O
+support	O
+this	O
+hypothesis	O
+,	O
+since	O
+unlike	O
+Weber	O
+and	O
+colleagues	O
+,	O
+we	O
+were	O
+able	O
+to	O
+detect	O
+significant	O
+amounts	O
+of	O
+Scp160p	O
+associated	O
+with	O
+polyribosomes	O
+without	O
+using	O
+detergents	O
+during	O
+preparation	O
+.	O
+
+There	O
+are	O
+several	O
+possible	O
+explanations	O
+for	O
+this	O
+discrepancy	O
+.	O
+
+First	O
+,	O
+the	O
+lysate	O
+buffer	O
+utilized	O
+by	O
+that	O
+group	O
+contained	O
+100	O
+mM	O
+NaCl	O
+,	O
+whereas	O
+our	O
+buffer	O
+contained	O
+50	O
+mM	O
+KCl	O
+.	O
+
+Our	O
+data	O
+shown	O
+in	O
+Figure	O
+3	O
+suggest	O
+that	O
+100	O
+mM	O
+NaCl	O
+may	O
+have	O
+caused	O
+an	O
+instability	O
+in	O
+the	O
+Scp160p	O
+-	O
+RNA	O
+interaction	O
+,	O
+leading	O
+to	O
+release	O
+from	O
+polyribosomes	O
+during	O
+their	O
+procedure	O
+.	O
+
+Secondly	O
+,	O
+Weber	O
+'	O
+s	O
+lysate	O
+buffer	O
+reportedly	O
+contained	O
+heparin	O
+to	O
+inhibit	O
+ribonucleases	O
+;	O
+a	O
+number	O
+of	O
+reports	O
+(	O
+28	O
+,	O
+29	O
+)	O
+suggest	O
+that	O
+heparin	O
+can	O
+disrupt	O
+RNA	O
+-	O
+protein	O
+interactions	O
+.	O
+
+Although	O
+we	O
+have	O
+not	O
+in	O
+the	O
+past	O
+included	O
+heparin	O
+in	O
+any	O
+of	O
+our	O
+experiments	O
+,	O
+we	O
+have	O
+observed	O
+disruption	O
+of	O
+the	O
+polyribosome	O
+association	O
+in	O
+buffer	O
+containing	O
+residual	O
+diethylpyrocarbonate	O
+,	O
+another	O
+inhibitor	O
+of	O
+ribonucleases	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Second	O
+,	O
+our	O
+data	O
+provide	O
+compelling	O
+evidence	O
+that	O
+Scp160p	O
+is	O
+released	O
+from	O
+polyribosomes	O
+as	O
+a	O
+component	O
+of	O
+an	O
+mRNP	O
+complex	O
+.	O
+
+Since	O
+Scp160p	O
+does	O
+not	O
+remain	O
+associated	O
+with	O
+either	O
+single	O
+ribosomes	O
+or	O
+ribosomal	O
+subunits	O
+following	O
+treatment	O
+with	O
+EDTA	O
+or	O
+RNase	O
+,	O
+it	O
+seems	O
+unlikely	O
+that	O
+Scp160p	O
+is	O
+a	O
+constitutive	O
+component	O
+of	O
+the	O
+translational	O
+machinery	O
+.	O
+
+Partial	O
+purification	O
+of	O
+the	O
+EDTA	O
+-	O
+resistant	O
+Scp160p	O
+complexes	O
+allowed	O
+us	O
+to	O
+demonstrate	O
+the	O
+presence	O
+of	O
+Pab1p	O
+but	O
+not	O
+Pub1p	O
+in	O
+these	O
+preparations	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+the	O
+idea	O
+that	O
+Scp160p	O
+associates	O
+with	O
+polyribosomes	O
+as	O
+a	O
+component	O
+of	O
+mRNP	O
+complexes	O
+.	O
+
+Previously	O
+,	O
+Scp160p	O
+had	O
+been	O
+shown	O
+to	O
+bind	O
+ribohomopolymers	O
+and	O
+rRNA	O
+in	O
+vitro	O
+,	O
+although	O
+the	O
+in	O
+vivo	O
+nucleic	O
+acid	O
+targets	O
+of	O
+Scp160p	O
+were	O
+unknown	O
+(	O
+5	O
+)	O
+.	O
+
+The	O
+presence	O
+of	O
+Pab1p	O
+in	O
+RNase	O
+-	O
+sensitive	O
+Scp160p	O
+complexes	O
+indicates	O
+that	O
+Scp160p	O
+is	O
+primarily	O
+bound	O
+to	O
+polyadenylated	O
+RNAs	O
+.	O
+
+Whether	O
+or	O
+not	O
+Scp160p	O
+binds	O
+only	O
+specific	O
+sets	O
+of	O
+mRNAs	O
+will	O
+be	O
+the	O
+subject	O
+of	O
+future	O
+studies	O
+.	O
+
+In	O
+addition	O
+to	O
+Scp160p	O
+and	O
+Pab1p	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+third	O
+component	O
+of	O
+the	O
+complex	O
+,	O
+the	O
+protein	O
+Bfr1p	O
+.	O
+
+The	O
+gene	O
+,	O
+BFR1	O
+,	O
+was	O
+originally	O
+identified	O
+in	O
+a	O
+screen	O
+for	O
+high	O
+-	O
+copy	O
+suppressors	O
+of	O
+Brefeldin	O
+-	O
+A	O
+induced	O
+lethality	O
+,	O
+suggesting	O
+a	O
+role	O
+in	O
+the	O
+secretory	O
+pathway	O
+(	O
+16	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+however	O
+,	O
+bfr1	O
+null	O
+mutants	O
+do	O
+not	O
+demonstrate	O
+any	O
+defects	O
+in	O
+the	O
+secretory	O
+pathway	O
+,	O
+but	O
+rather	O
+display	O
+similar	O
+phenotypes	O
+to	O
+scp160	O
+null	O
+mutants	O
+,	O
+most	O
+notably	O
+increased	O
+ploidy	O
+and	O
+increased	O
+cell	O
+size	O
+(	O
+16	O
+)	O
+.	O
+
+It	O
+is	O
+therefore	O
+unclear	O
+whether	O
+Bfr1p	O
+is	O
+capable	O
+of	O
+functioning	O
+in	O
+both	O
+RNA	O
+metabolism	O
+and	O
+secretion	O
+directly	O
+,	O
+or	O
+if	O
+the	O
+Scp160p	O
+-	O
+Bfr1p	O
+complex	O
+regulates	O
+the	O
+expression	O
+of	O
+one	O
+or	O
+more	O
+secretory	O
+genes	O
+at	O
+the	O
+post	O
+-	O
+transcriptional	O
+level	O
+.	O
+
+Additionally	O
+,	O
+two	O
+-	O
+hybrid	O
+analysis	O
+indicated	O
+an	O
+interaction	O
+of	O
+Bfr1p	O
+with	O
+the	O
+protein	O
+Bbp1p	O
+,	O
+a	O
+component	O
+of	O
+the	O
+mitotic	O
+spindle	O
+apparatus	O
+(	O
+30	O
+)	O
+.	O
+
+While	O
+Bbp1p	O
+is	O
+an	O
+essential	O
+gene	O
+,	O
+overexpression	O
+leads	O
+to	O
+a	O
+phenotype	O
+similar	O
+to	O
+both	O
+bfr1	O
+and	O
+scp160	O
+null	O
+strains	O
+(	O
+30	O
+)	O
+.	O
+
+Future	O
+work	O
+will	O
+address	O
+the	O
+functional	O
+relationship	O
+between	O
+Scp160p	O
+and	O
+Bfr1p	O
+including	O
+the	O
+possibility	O
+that	O
+these	O
+proteins	O
+represent	O
+a	O
+regulatory	O
+mechanism	O
+connecting	O
+the	O
+translational	O
+machinery	O
+with	O
+cell	O
+division	O
+and	O
+/	O
+or	O
+the	O
+secretory	O
+pathway	O
+.	O
+
+Following	O
+treatment	O
+with	O
+either	O
+RNase	O
+or	O
+>	O
+150	O
+mM	O
+NaCl	O
+,	O
+Scp160p	O
+remained	O
+as	O
+an	O
+apparent	O
+~	O
+450	O
+kDa	O
+species	O
+.	O
+
+Considering	O
+that	O
+purified	O
+Scp160p	O
+alone	O
+also	O
+migrates	O
+at	O
+this	O
+size	O
+,	O
+we	O
+conclude	O
+that	O
+this	O
+apparent	O
+complex	O
+may	O
+consist	O
+only	O
+of	O
+Scp160p	O
+,	O
+although	O
+the	O
+presence	O
+of	O
+other	O
+small	O
+components	O
+cannot	O
+be	O
+ruled	O
+out	O
+at	O
+this	O
+time	O
+.	O
+
+Furthermore	O
+,	O
+by	O
+utilizing	O
+yeast	B
+co	O
+-	O
+expressing	O
+two	O
+distinct	O
+epitope	O
+-	O
+tagged	O
+versions	O
+of	O
+Scp160p	O
+,	O
+we	O
+have	O
+ruled	O
+out	O
+the	O
+possibility	O
+of	O
+self	O
+-	O
+association	O
+of	O
+Scp160p	O
+.	O
+
+Although	O
+both	O
+tagged	O
+proteins	O
+appear	O
+functional	O
+,	O
+it	O
+remains	O
+a	O
+formal	O
+possibility	O
+that	O
+the	O
+tags	O
+somehow	O
+prevented	O
+formation	O
+of	O
+FLAG	O
+-	O
+HA	O
+hetero	O
+-	O
+complexes	O
+.	O
+
+Nonetheless	O
+,	O
+it	O
+seems	O
+most	O
+likely	O
+that	O
+native	O
+Scp160p	O
+monomers	O
+may	O
+simply	O
+migrate	O
+aberrantly	O
+under	O
+native	O
+conditions	O
+due	O
+to	O
+an	O
+unusual	O
+shape	O
+or	O
+some	O
+other	O
+physical	O
+property	O
+.	O
+
+In	O
+conclusion	O
+we	O
+have	O
+shown	O
+convincing	O
+evidence	O
+that	O
+Scp160p	O
+exists	O
+in	O
+yeast	B
+cytoplasmic	O
+extracts	O
+primarily	O
+associated	O
+with	O
+polyribosomes	O
+.	O
+
+We	O
+have	O
+purified	O
+Scp160p	O
+following	O
+disruption	O
+of	O
+polyribosomes	O
+with	O
+EDTA	O
+,	O
+and	O
+identified	O
+two	O
+associated	O
+proteins	O
+:	O
+Pab1p	O
+and	O
+Bfr1p	O
+.	O
+
+The	O
+presence	O
+of	O
+Pab1p	O
+suggests	O
+that	O
+Scp160p	O
+associates	O
+with	O
+polyribosomes	O
+as	O
+a	O
+component	O
+of	O
+an	O
+mRNP	O
+,	O
+demonstrating	O
+Scp160p	O
+to	O
+be	O
+the	O
+first	O
+S	B
+.	I
+cerevisiae	I
+multiple	O
+-	O
+KH	O
+domain	O
+protein	O
+characterized	O
+to	O
+function	O
+in	O
+this	O
+way	O
+.	O
+
+HP1	O
+modulates	O
+the	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulators	O
+in	O
+Drosophila	B
+melanogaster	I
+
+Abstract	O
+
+Heterochromatin	O
+protein	O
+1	O
+(	O
+HP1	O
+)	O
+was	O
+originally	O
+described	O
+as	O
+a	O
+non	O
+-	O
+histone	O
+chromosomal	O
+protein	O
+and	O
+is	O
+required	O
+for	O
+transcriptional	O
+gene	O
+silencing	O
+and	O
+the	O
+formation	O
+of	O
+heterochromatin	O
+.	O
+
+Although	O
+it	O
+is	O
+localized	O
+primarily	O
+at	O
+pericentric	O
+heterochromatin	O
+,	O
+a	O
+scattered	O
+distribution	O
+over	O
+a	O
+large	O
+number	O
+of	O
+euchromatic	O
+loci	O
+is	O
+also	O
+evident	O
+.	O
+
+Here	O
+,	O
+we	O
+provide	O
+evidence	O
+that	O
+Drosophila	B
+HP1	O
+is	O
+essential	O
+for	O
+the	O
+maintenance	O
+of	O
+active	O
+transcription	O
+of	O
+euchromatic	O
+genes	O
+functionally	O
+involved	O
+in	O
+cell	O
+-	O
+cycle	O
+progression	O
+,	O
+including	O
+those	O
+required	O
+for	O
+DNA	O
+replication	O
+and	O
+mitosis	O
+.	O
+
+Depletion	O
+of	O
+HP1	O
+in	O
+proliferating	O
+embryonic	O
+cells	O
+caused	O
+aberrant	O
+progression	O
+of	O
+the	O
+cell	O
+cycle	O
+at	O
+S	O
+phase	O
+and	O
+G2	O
+/	O
+M	O
+phase	O
+,	O
+linked	O
+to	O
+aberrant	O
+chromosome	O
+segregation	O
+,	O
+cytokinesis	O
+,	O
+and	O
+an	O
+increase	O
+in	O
+apoptosis	O
+.	O
+
+The	O
+chromosomal	O
+distribution	O
+of	O
+Aurora	O
+B	O
+,	O
+and	O
+the	O
+level	O
+of	O
+phosphorylation	O
+of	O
+histone	O
+H3	O
+serine	O
+10	O
+were	O
+also	O
+altered	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+.	O
+
+Using	O
+chromatin	O
+immunoprecipitation	O
+analysis	O
+,	O
+we	O
+further	O
+demonstrate	O
+that	O
+the	O
+promoters	O
+of	O
+a	O
+number	O
+of	O
+cell	O
+-	O
+cycle	O
+regulator	O
+genes	O
+are	O
+bound	O
+to	O
+HP1	O
+,	O
+supporting	O
+a	O
+direct	O
+role	O
+for	O
+HP1	O
+in	O
+their	O
+active	O
+transcription	O
+.	O
+
+Overall	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+HP1	O
+is	O
+essential	O
+for	O
+the	O
+maintenance	O
+of	O
+cell	O
+-	O
+cycle	O
+progression	O
+and	O
+the	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulatory	O
+genes	O
+.	O
+
+The	O
+results	O
+also	O
+support	O
+the	O
+view	O
+that	O
+HP1	O
+is	O
+a	O
+positive	O
+regulator	O
+of	O
+transcription	O
+in	O
+euchromatin	O
+.	O
+
+INTRODUCTION	O
+
+Chromatin	O
+in	O
+higher	O
+eukaryotes	O
+is	O
+subdivided	O
+into	O
+different	O
+functional	O
+compartments	O
+termed	O
+heterochromatin	O
+and	O
+euchromatin	O
+(	O
+1	O
+)	O
+.	O
+
+Heterochromatin	O
+differs	O
+from	O
+euchromatin	O
+in	O
+its	O
+DNA	O
+composition	O
+,	O
+replication	O
+timing	O
+,	O
+condensation	O
+throughout	O
+the	O
+cell	O
+cycle	O
+,	O
+and	O
+its	O
+ability	O
+to	O
+silence	O
+euchromatic	O
+genes	O
+placed	O
+adjacent	O
+to	O
+or	O
+within	O
+its	O
+territory	O
+,	O
+often	O
+described	O
+as	O
+position	O
+-	O
+effect	O
+-	O
+variegation	O
+(	O
+PEV	O
+)	O
+(	O
+2	O
+)	O
+.	O
+
+Heterochromatin	O
+protein	O
+1	O
+(	O
+HP1	O
+)	O
+was	O
+the	O
+first	O
+protein	O
+identified	O
+in	O
+Drosophila	B
+melanogaster	I
+as	O
+a	O
+heterochromatin	O
+-	O
+associated	O
+protein	O
+(	O
+3	O
+)	O
+;	O
+the	O
+corresponding	O
+gene	O
+has	O
+been	O
+cloned	O
+from	O
+a	O
+number	O
+of	O
+organisms	O
+and	O
+is	O
+highly	O
+conserved	O
+from	O
+yeast	B
+to	O
+human	B
+(	O
+4	O
+)	O
+.	O
+
+Polytene	O
+chromosome	O
+staining	O
+showed	O
+that	O
+,	O
+in	O
+Drosophila	B
+,	O
+HP1	O
+is	O
+distributed	O
+mainly	O
+in	O
+pericentric	O
+heterochromatin	O
+,	O
+telomeric	O
+heterochromatin	O
+,	O
+the	O
+banded	O
+small	O
+fourth	O
+chromosome	O
+(	O
+5	O
+-	O
+8	O
+)	O
+,	O
+as	O
+well	O
+as	O
+~	O
+200	O
+individual	O
+loci	O
+scattered	O
+throughout	O
+the	O
+euchromatic	O
+chromosomal	O
+arms	O
+(	O
+5	O
+)	O
+.	O
+
+The	O
+gene	O
+encoding	O
+HP1	O
+in	O
+D	B
+.	I
+melanogaster	I
+,	O
+Su	O
+(	O
+var	O
+)	O
+2	O
+-	O
+5	O
+,	O
+was	O
+isolated	O
+as	O
+a	O
+suppressor	O
+of	O
+PEV	O
+(	O
+9	O
+-	O
+11	O
+)	O
+.	O
+
+The	O
+protein	O
+contains	O
+a	O
+highly	O
+conserved	O
+motif	O
+,	O
+the	O
+chromo	O
+(	O
+chromatin	O
+organization	O
+modifier	O
+)	O
+domain	O
+,	O
+similar	O
+to	O
+Polycomb	O
+(	O
+Pc	O
+)	O
+,	O
+a	O
+repressor	O
+of	O
+homeotic	O
+genes	O
+(	O
+12	O
+)	O
+.	O
+
+The	O
+association	O
+between	O
+HP1	O
+and	O
+pericentric	O
+heterochromatin	O
+is	O
+believed	O
+to	O
+occur	O
+via	O
+the	O
+chromo	O
+domain	O
+of	O
+HP1	O
+and	O
+the	O
+N	O
+-	O
+terminal	O
+tail	O
+of	O
+histone	O
+H3	O
+methylated	O
+at	O
+lysine	O
+9	O
+(	O
+13	O
+,	O
+14	O
+)	O
+,	O
+generated	O
+by	O
+histone	O
+methyltransferase	O
+-	O
+Su	O
+(	O
+var	O
+)	O
+3	O
+-	O
+9	O
+,	O
+a	O
+partner	O
+of	O
+HP1	O
+in	O
+pericentric	O
+heterochromatin	O
+(	O
+15	O
+)	O
+.	O
+
+The	O
+C	O
+-	O
+terminal	O
+chromo	O
+'	O
+shadow	O
+'	O
+domain	O
+of	O
+HP1	O
+interacts	O
+with	O
+other	O
+silencing	O
+complexes	O
+to	O
+suppress	O
+local	O
+transcriptional	O
+activity	O
+(	O
+15	O
+-	O
+18	O
+)	O
+.	O
+
+However	O
+,	O
+studies	O
+of	O
+HP1	O
+chromosomal	O
+distribution	O
+also	O
+showed	O
+that	O
+HP1	O
+does	O
+not	O
+always	O
+co	O
+-	O
+localize	O
+with	O
+lysine	O
+9	O
+methylated	O
+histone	O
+H3	O
+or	O
+Su	O
+(	O
+var	O
+)	O
+3	O
+-	O
+9	O
+,	O
+especially	O
+in	O
+euchromatic	O
+regions	O
+(	O
+19	O
+-	O
+21	O
+)	O
+;	O
+in	O
+some	O
+cases	O
+,	O
+HP1	O
+is	O
+found	O
+directly	O
+bound	O
+to	O
+DNA	O
+(	O
+22	O
+,	O
+23	O
+)	O
+.	O
+
+All	O
+these	O
+features	O
+argue	O
+for	O
+distinct	O
+roles	O
+for	O
+HP1	O
+in	O
+chromatin	O
+and	O
+in	O
+epigenetic	O
+gene	O
+regulation	O
+.	O
+
+HP1	O
+is	O
+believed	O
+to	O
+be	O
+an	O
+essential	O
+structural	O
+protein	O
+protecting	O
+the	O
+integrity	O
+of	O
+chromosomes	O
+during	O
+cell	O
+division	O
+(	O
+8	O
+,	O
+24	O
+)	O
+.	O
+
+Swi6	O
+,	O
+the	O
+homolog	O
+of	O
+HP1	O
+in	O
+fission	B
+yeast	I
+,	O
+is	O
+dispensable	O
+for	O
+survival	O
+,	O
+but	O
+its	O
+deletion	O
+results	O
+in	O
+lagging	O
+chromosomes	O
+during	O
+anaphase	O
+,	O
+and	O
+a	O
+high	O
+rate	O
+of	O
+chromosome	O
+loss	O
+(	O
+25	O
+,	O
+26	O
+)	O
+.	O
+
+Mutations	O
+of	O
+HP1	O
+in	O
+D	B
+.	I
+melanogaster	I
+result	O
+in	O
+late	O
+larval	O
+lethality	O
+,	O
+chromosome	O
+breakages	O
+/	O
+loss	O
+,	O
+telomere	O
+fusion	O
+and	O
+a	O
+high	O
+frequency	O
+of	O
+cells	O
+with	O
+abnormal	O
+anaphase	O
+(	O
+8	O
+,	O
+27	O
+)	O
+.	O
+
+Null	O
+alleles	O
+of	O
+the	O
+HP1	O
+functional	O
+partner	O
+in	O
+mice	B
+(	O
+SUVAR39	O
+)	O
+also	O
+showed	O
+various	O
+chromosomal	O
+defects	O
+(	O
+28	O
+)	O
+,	O
+supporting	O
+a	O
+conserved	O
+role	O
+for	O
+heterochromatin	O
+proteins	O
+in	O
+the	O
+regulation	O
+of	O
+chromosome	O
+dynamics	O
+during	O
+cell	O
+-	O
+cycle	O
+progression	O
+.	O
+
+However	O
+,	O
+the	O
+mechanism	O
+(	O
+s	O
+)	O
+involved	O
+remains	O
+to	O
+be	O
+understood	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+utilized	O
+Drosophila	B
+embryonic	O
+Kc	O
+cells	O
+and	O
+an	O
+RNA	O
+interference	O
+(	O
+RNAi	O
+)	O
+-	O
+based	O
+approach	O
+to	O
+demonstrate	O
+that	O
+HP1	O
+plays	O
+an	O
+important	O
+role	O
+at	O
+S	O
+phase	O
+and	O
+G2	O
+/	O
+M	O
+phases	O
+during	O
+the	O
+cell	O
+cycle	O
+.	O
+
+We	O
+further	O
+show	O
+that	O
+nearly	O
+one	O
+-	O
+third	O
+of	O
+known	O
+/	O
+predicted	O
+cell	O
+-	O
+cycle	O
+regulators	O
+require	O
+HP1	O
+to	O
+maintain	O
+their	O
+active	O
+transcription	O
+.	O
+
+These	O
+genes	O
+include	O
+MCMs	O
+,	O
+Orc4	O
+,	O
+CDC45L	O
+,	O
+INCENP	O
+,	O
+Aurora	O
+B	O
+,	O
+CAF1	O
+,	O
+Bub1	O
+,	O
+Bub3	O
+and	O
+a	O
+few	O
+other	O
+cell	O
+-	O
+cycle	O
+regulators	O
+.	O
+
+ChIP	O
+analysis	O
+suggests	O
+that	O
+HP1	O
+plays	O
+a	O
+direct	O
+role	O
+in	O
+their	O
+transcription	O
+.	O
+
+Therefore	O
+,	O
+the	O
+results	O
+of	O
+this	O
+study	O
+provide	O
+an	O
+alternative	O
+explanation	O
+for	O
+the	O
+specific	O
+role	O
+of	O
+HP1	O
+in	O
+the	O
+regulation	O
+of	O
+chromatin	O
+dynamics	O
+and	O
+in	O
+cell	O
+-	O
+cycle	O
+progression	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+
+RNAi	O
+in	O
+Kc	O
+cells	O
+
+Drosophila	B
+Kc	O
+cells	O
+were	O
+routinely	O
+cultured	O
+at	O
+25	O
+degrees	O
+C	O
+in	O
+Schneider	O
+Drosophila	B
+medium	O
+(	O
+GIBCO	O
+)	O
+supplemented	O
+with	O
+10	O
+%	O
+fetal	O
+calf	O
+serum	O
+,	O
+160	O
+mu	O
+g	O
+/	O
+ml	O
+penicillin	O
+,	O
+250	O
+mu	O
+g	O
+/	O
+ml	O
+streptomycin	O
+,	O
+and	O
+4	O
+mM	O
+l	O
+-	O
+glutamine	O
+.	O
+
+Double	O
+-	O
+stranded	O
+RNA	O
+(	O
+dsRNA	O
+)	O
+of	O
+HP1	O
+was	O
+generated	O
+by	O
+incubation	O
+of	O
+single	O
+-	O
+stranded	O
+RNA	O
+in	O
+annealing	O
+buffer	O
+(	O
+100	O
+mM	O
+potassium	O
+acetate	O
+,	O
+30	O
+mM	O
+HEPES	O
+-	O
+KOH	O
+,	O
+pH	O
+7	O
+.	O
+4	O
+,	O
+2	O
+mM	O
+magnesium	O
+acetate	O
+)	O
+for	O
+3	O
+min	O
+at	O
+95	O
+degrees	O
+C	O
+and	O
+then	O
+placed	O
+in	O
+a	O
+beaker	O
+with	O
+water	O
+at	O
+75	O
+degrees	O
+C	O
+and	O
+allowed	O
+to	O
+cool	O
+slowly	O
+to	O
+room	O
+temperature	O
+.	O
+
+The	O
+detailed	O
+procedure	O
+of	O
+RNAi	O
+was	O
+carried	O
+out	O
+according	O
+to	O
+the	O
+established	O
+protocols	O
+(	O
+)	O
+.	O
+
+Briefly	O
+,	O
+Kc	O
+cells	O
+were	O
+seeded	O
+in	O
+a	O
+six	O
+-	O
+well	O
+dish	O
+using	O
+serum	O
+-	O
+free	O
+medium	O
+at	O
+1	O
+x	O
+106	O
+cells	O
+/	O
+ml	O
+.	O
+
+HP1	O
+dsRNA	O
+(	O
+5	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+was	O
+added	O
+to	O
+the	O
+cultured	O
+Kc	O
+cells	O
+.	O
+
+After	O
+60	O
+min	O
+at	O
+room	O
+temperature	O
+,	O
+2	O
+ml	O
+of	O
+medium	O
+containing	O
+10	O
+%	O
+serum	O
+was	O
+added	O
+to	O
+each	O
+well	O
+and	O
+the	O
+plates	O
+transferred	O
+to	O
+25	O
+degrees	O
+C	O
+for	O
+up	O
+to	O
+8	O
+days	O
+.	O
+
+Western	O
+blotting	O
+and	O
+RT	O
+-	O
+PCR	O
+were	O
+carried	O
+out	O
+using	O
+the	O
+extract	O
+/	O
+total	O
+RNA	O
+isolated	O
+from	O
+control	O
+and	O
+dsRNA	O
+-	O
+treated	O
+cells	O
+on	O
+days	O
+2	O
+,	O
+6	O
+and	O
+8	O
+.	O
+
+Cell	O
+-	O
+cycle	O
+and	O
+apoptosis	O
+analysis	O
+
+The	O
+procedure	O
+for	O
+flow	O
+cytometric	O
+analysis	O
+of	O
+Kc	O
+cells	O
+followed	O
+that	O
+in	O
+the	O
+manual	O
+provided	O
+with	O
+the	O
+BrdU	O
+flow	O
+kit	O
+(	O
+BD	O
+PharMingen	O
+)	O
+.	O
+
+The	O
+cells	O
+were	O
+fed	O
+with	O
+BrdU	O
+for	O
+4	O
+h	O
+,	O
+then	O
+scraped	O
+and	O
+collected	O
+.	O
+
+Fluorescence	O
+was	O
+measured	O
+using	O
+a	O
+FACSCalibur	O
+(	O
+Becton	O
+Dickinson	O
+)	O
+.	O
+
+Data	O
+collection	O
+and	O
+analysis	O
+were	O
+performed	O
+using	O
+CellQuest	O
+software	O
+.	O
+
+Electrophoresis	O
+and	O
+immunoblotting	O
+
+Cell	O
+extracts	O
+(	O
+15	O
+mu	O
+g	O
+)	O
+were	O
+fractionated	O
+by	O
+10	O
+%	O
+SDS	O
+-	O
+PAGE	O
+,	O
+then	O
+transferred	O
+to	O
+Hybond	O
+-	O
+P	O
+PVDF	O
+membranes	O
+(	O
+Amersham	O
+)	O
+and	O
+probed	O
+with	O
+primary	O
+antibodies	O
+(	O
+CIA9	O
+)	O
+,	O
+and	O
+secondary	O
+antibodies	O
+(	O
+anti	O
+-	O
+rabbit	B
+or	O
+anti	O
+-	O
+mouse	B
+horseradish	B
+peroxidase	O
+-	O
+conjugated	O
+IgG	O
+)	O
+,	O
+obtained	O
+from	O
+Jackson	O
+Immunoresearch	O
+Laboratories	O
+.	O
+
+Enhanced	O
+chemiluminescence	O
+reagents	O
+(	O
+Amersham	O
+Pharmacia	O
+Biotech	O
+)	O
+were	O
+used	O
+for	O
+signal	O
+detection	O
+.	O
+
+For	O
+the	O
+analysis	O
+of	O
+H3	O
+ser10	O
+phosphorylation	O
+,	O
+we	O
+used	O
+whole	O
+-	O
+cell	O
+extracts	O
+from	O
+700	O
+000	O
+Kc	O
+cells	O
+(	O
+control	O
+and	O
+RNAi	O
+at	O
+day	O
+8	O
+)	O
+.	O
+
+Western	O
+blotting	O
+was	O
+performed	O
+using	O
+polyclonal	O
+antibodies	O
+against	O
+ser10	O
+-	O
+phosphorylated	O
+histone	O
+H3	O
+at	O
+a	O
+dilution	O
+of	O
+1	O
+:	O
+1000	O
+(	O
+Upstate	O
+)	O
+.	O
+
+Kc	O
+control	O
+cells	O
+arrested	O
+in	O
+mitosis	O
+by	O
+incubation	O
+in	O
+25	O
+micro	O
+M	O
+colchicine	O
+(	O
+Sigma	O
+)	O
+for	O
+24	O
+h	O
+were	O
+also	O
+analyzed	O
+for	O
+comparison	O
+.	O
+
+Immunofluorescence	O
+
+Kc	O
+cells	O
+were	O
+seeded	O
+onto	O
+polylysine	O
+slides	O
+,	O
+fixed	O
+with	O
+4	O
+%	O
+formaldehyde	O
+for	O
+15	O
+min	O
+and	O
+permeabilized	O
+with	O
+0	O
+.	O
+5	O
+%	O
+Triton	O
+X	O
+-	O
+100	O
+for	O
+5	O
+min	O
+.	O
+
+The	O
+incubation	O
+with	O
+primary	O
+antibodies	O
+was	O
+carried	O
+out	O
+in	O
+blocking	O
+solution	O
+for	O
+1	O
+h	O
+.	O
+
+For	O
+staining	O
+of	O
+mitotic	O
+cells	O
+,	O
+the	O
+cells	O
+were	O
+permeabilized	O
+using	O
+PBST	O
+(	O
+PBS	O
+containing	O
+0	O
+.	O
+3	O
+%	O
+Triton	O
+X	O
+-	O
+100	O
+)	O
+and	O
+stained	O
+with	O
+polyclonal	O
+antibody	O
+against	O
+Drosophila	B
+Aurora	O
+B	O
+at	O
+1	O
+:	O
+200	O
+dilution	O
+and	O
+monoclonal	O
+mouse	B
+at	O
+anti	O
+-	O
+beta	O
+-	O
+tubulin	O
+1	O
+:	O
+300	O
+dilution	O
+(	O
+Chemicon	O
+International	O
+)	O
+as	O
+primary	O
+antibodies	O
+.	O
+
+Secondary	O
+antibodies	O
+were	O
+anti	O
+-	O
+rabbit	B
+coupled	O
+with	O
+Alexa	O
+488	O
+(	O
+1	O
+:	O
+500	O
+)	O
+and	O
+anti	O
+-	O
+mouse	B
+coupled	O
+to	O
+Alexa	O
+546	O
+(	O
+1	O
+:	O
+500	O
+)	O
+(	O
+Molecular	O
+Probes	O
+,	O
+Eugene	O
+,	O
+Oregon	O
+)	O
+.	O
+
+Images	O
+were	O
+acquired	O
+using	O
+a	O
+confocal	O
+LSM510	O
+META	O
+microscope	O
+(	O
+Zeiss	O
+)	O
+.	O
+
+Stacks	O
+of	O
+images	O
+were	O
+analyzed	O
+using	O
+the	O
+IMARIS	O
+4	O
+.	O
+0	O
+program	O
+(	O
+Media	O
+cybernetics	O
+,	O
+Carlsbad	O
+,	O
+CA	O
+)	O
+.	O
+
+Antibodies	O
+
+Affinity	O
+-	O
+purified	O
+polyclonal	O
+antibodies	O
+of	O
+HP1	O
+(	O
+rabbit	B
+#	O
+192	O
+and	O
+#	O
+187	O
+,	O
+5	O
+mu	O
+g	O
+)	O
+and	O
+5	O
+mu	O
+g	O
+of	O
+polyclonal	O
+anti	O
+-	O
+HA	O
+antibodies	O
+(	O
+Sigma	O
+)	O
+were	O
+used	O
+in	O
+each	O
+ChIP	O
+reaction	O
+.	O
+
+The	O
+specificity	O
+of	O
+the	O
+HP1	O
+polyclonal	O
+antibodies	O
+was	O
+determined	O
+using	O
+various	O
+approaches	O
+,	O
+including	O
+western	O
+blotting	O
+assay	O
+,	O
+immunofluorescence	O
+staining	O
+and	O
+immunoprecipitation	O
+to	O
+pull	O
+down	O
+HP1	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+monoclonal	O
+antibody	O
+HP1	O
+-	O
+CIA9	O
+(	O
+5	O
+)	O
+was	O
+used	O
+at	O
+a	O
+dilution	O
+of	O
+1	O
+:	O
+20	O
+in	O
+immunoblotting	O
+assays	O
+.	O
+
+Microarray	O
+analysis	O
+and	O
+RT	O
+-	O
+PCR	O
+
+Total	O
+RNA	O
+was	O
+isolated	O
+from	O
+control	O
+and	O
+HP1	O
+-	O
+depleted	O
+Kc	O
+cells	O
+at	O
+day	O
+8	O
+using	O
+an	O
+RNeasy	O
+kit	O
+(	O
+Qiagen	O
+)	O
+.	O
+
+RNA	O
+labeling	O
+and	O
+microarray	O
+data	O
+analysis	O
+followed	O
+the	O
+standard	O
+protocol	O
+from	O
+Affymetrix	O
+.	O
+
+We	O
+used	O
+ANOVA	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+to	O
+assess	O
+the	O
+expression	O
+confidence	O
+for	O
+each	O
+gene	O
+.	O
+
+For	O
+RT	O
+-	O
+PCR	O
+analysis	O
+,	O
+poly	O
+(	O
+A	O
+)	O
++	O
+mRNA	O
+was	O
+purified	O
+with	O
+the	O
+Oligotex	O
+Direct	O
+mRNA	O
+kit	O
+(	O
+Qiagen	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+.	O
+
+The	O
+purified	O
+poly	O
+(	O
+A	O
+)	O
++	O
+RNA	O
+was	O
+reverse	O
+transcribed	O
+using	O
+the	O
+Thermoscript	O
+kit	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+The	O
+cDNA	O
+was	O
+then	O
+used	O
+for	O
+PCR	O
+amplification	O
+for	O
+35	O
+cycles	O
+with	O
+gene	O
+-	O
+specific	O
+primers	O
+.	O
+
+PCR	O
+products	O
+were	O
+scanned	O
+after	O
+electrophoretic	O
+separation	O
+with	O
+a	O
+Typhoon	O
+Scanner	O
+,	O
+quantified	O
+using	O
+ImageQuant	O
+software	O
+(	O
+Amersham	O
+Biosciences	O
+)	O
+and	O
+normalized	O
+for	O
+amplification	O
+of	O
+the	O
+Actin5c	O
+transcript	O
+.	O
+
+The	O
+sequence	O
+of	O
+primers	O
+used	O
+for	O
+RT	O
+-	O
+PCR	O
+and	O
+ChIP	O
+analysis	O
+are	O
+provided	O
+in	O
+the	O
+Supplementary	O
+Material	O
+.	O
+
+ChIP	O
+
+ChIP	O
+was	O
+performed	O
+according	O
+to	O
+Orlando	O
+et	O
+al	O
+.	O
+
+(	O
+29	O
+)	O
+and	O
+the	O
+protocol	O
+provided	O
+by	O
+Upstate	O
+(	O
+)	O
+with	O
+some	O
+modifications	O
+.	O
+
+In	O
+brief	O
+,	O
+1	O
+-	O
+2	O
+x	O
+108	O
+Kc	O
+cells	O
+were	O
+prepared	O
+and	O
+fixed	O
+in	O
+1	O
+%	O
+formaldehyde	O
+.	O
+
+Nuclei	O
+were	O
+isolated	O
+according	O
+to	O
+a	O
+standard	O
+procedure	O
+in	O
+Current	O
+Protocols	O
+(	O
+)	O
+,	O
+then	O
+resuspended	O
+in	O
+1	O
+.	O
+7	O
+ml	O
+of	O
+lysis	O
+buffer	O
+(	O
+50	O
+mM	O
+Tris	O
+,	O
+pH	O
+8	O
+.	O
+0	O
+,	O
+10	O
+mM	O
+EDTA	O
+,	O
+1	O
+%	O
+SDS	O
+and	O
+protease	O
+inhibitors	O
+)	O
+and	O
+sonicated	O
+using	O
+a	O
+Branson	O
+sonifier	O
+250	O
+.	O
+
+Chromatin	O
+fractions	O
+in	O
+the	O
+size	O
+range	O
+0	O
+.	O
+2	O
+-	O
+0	O
+.	O
+8	O
+kb	O
+were	O
+used	O
+to	O
+perform	O
+immunoprecipitation	O
+experiments	O
+.	O
+
+We	O
+used	O
+5	O
+mu	O
+g	O
+affinity	O
+-	O
+purified	O
+polyclonal	O
+antibodies	O
+(	O
+#	O
+192	O
+and	O
+#	O
+182	O
+for	O
+HP1	O
+;	O
+HA	O
+antibody	O
+for	O
+control	O
+)	O
+and	O
+1	O
+ml	O
+of	O
+salmon	O
+sperm	O
+DNA	O
+/	O
+protein	O
+-	O
+A	O
+-	O
+agarose	O
+(	O
+Upstate	O
+)	O
+pre	O
+-	O
+cleared	O
+chromatin	O
+lysate	O
+in	O
+each	O
+reaction	O
+.	O
+
+The	O
+mixture	O
+was	O
+then	O
+rotated	O
+at	O
+4	O
+degrees	O
+C	O
+overnight	O
+and	O
+the	O
+recovered	O
+beads	O
+were	O
+washed	O
+twice	O
+with	O
+1	O
+ml	O
+of	O
+Low	O
+salt	O
+buffer	O
+(	O
+Upstate	O
+)	O
+,	O
+once	O
+with	O
+High	O
+salt	O
+buffer	O
+(	O
+Upstate	O
+)	O
+,	O
+once	O
+with	O
+LiCl	O
+buffer	O
+(	O
+Upstate	O
+)	O
+and	O
+twice	O
+with	O
+TE	O
+at	O
+4	O
+degrees	O
+C	O
+for	O
+8	O
+min	O
+.	O
+
+ChIP	O
+DNA	O
+was	O
+extracted	O
+according	O
+to	O
+the	O
+standard	O
+procedures	O
+(	O
+29	O
+)	O
+.	O
+
+RESULTS	O
+
+Depletion	O
+of	O
+HP1	O
+in	O
+Drosophila	B
+Kc	O
+cells	O
+
+Various	O
+chromosomal	O
+defects	O
+in	O
+the	O
+cell	O
+cycle	O
+have	O
+been	O
+observed	O
+in	O
+embryos	O
+or	O
+larval	O
+tissues	O
+of	O
+Drosophila	B
+HP1	O
+mutants	O
+(	O
+8	O
+,	O
+27	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+presence	O
+of	O
+maternally	O
+loaded	O
+HP1	O
+in	O
+embryos	O
+and	O
+the	O
+lethality	O
+of	O
+HP1	O
+mutants	O
+at	O
+late	O
+larval	O
+stages	O
+have	O
+so	O
+far	O
+precluded	O
+a	O
+systematic	O
+study	O
+of	O
+the	O
+role	O
+of	O
+HP1	O
+in	O
+cell	O
+-	O
+cycle	O
+regulation	O
+.	O
+
+Therefore	O
+,	O
+we	O
+used	O
+Drosophila	B
+Kc	O
+cells	O
+,	O
+a	O
+cell	O
+line	O
+derived	O
+from	O
+Drosophila	B
+embryos	O
+,	O
+as	O
+a	O
+model	O
+system	O
+to	O
+address	O
+this	O
+problem	O
+.	O
+
+HP1	O
+transcripts	O
+were	O
+depleted	O
+using	O
+an	O
+RNAi	O
+-	O
+based	O
+approach	O
+(	O
+see	O
+Materials	O
+and	O
+Methods	O
+)	O
+.	O
+
+The	O
+reduction	O
+in	O
+HP1	O
+expression	O
+was	O
+measured	O
+both	O
+by	O
+RT	O
+-	O
+PCR	O
+and	O
+by	O
+western	O
+blotting	O
+analysis	O
+(	O
+Figure	O
+1A	O
+)	O
+.	O
+
+A	O
+significant	O
+reduction	O
+in	O
+the	O
+HP1	O
+expression	O
+was	O
+already	O
+evident	O
+after	O
+2	O
+days	O
+treatment	O
+with	O
+HP1	O
+dsRNA	O
+.	O
+
+Cells	O
+at	O
+day	O
+8	O
+showed	O
+a	O
+reduction	O
+in	O
+HP1	O
+of	O
+~	O
+90	O
+%	O
+(	O
+Figure	O
+1A	O
+)	O
+and	O
+were	O
+therefore	O
+used	O
+in	O
+all	O
+subsequent	O
+experiments	O
+.	O
+
+Cell	O
+-	O
+cycle	O
+progression	O
+at	O
+S	O
+and	O
+G2	O
+/	O
+M	O
+phase	O
+is	O
+altered	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+
+The	O
+impact	O
+of	O
+HP1	O
+loss	O
+on	O
+the	O
+cell	O
+cycle	O
+of	O
+Kc	O
+cells	O
+was	O
+determined	O
+using	O
+cell	O
+-	O
+cycle	O
+profile	O
+analysis	O
+of	O
+HP1	O
+-	O
+depleted	O
+and	O
+control	O
+cells	O
+.	O
+
+The	O
+percentage	O
+of	O
+cells	O
+in	O
+S	O
+phase	O
+was	O
+determined	O
+by	O
+BrdU	O
+incorporation	O
+,	O
+and	O
+total	O
+DNA	O
+content	O
+by	O
+7	O
+-	O
+amino	O
+-	O
+actinomycin	O
+(	O
+7	O
+-	O
+AAD	O
+)	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+the	O
+depletion	O
+of	O
+HP1	O
+(	O
+day	O
+8	O
+)	O
+caused	O
+a	O
+decrease	O
+in	O
+S	O
+-	O
+phase	O
+cells	O
+of	O
+at	O
+least	O
+4	O
+-	O
+fold	O
+,	O
+and	O
+a	O
+2	O
+-	O
+fold	O
+decrease	O
+in	O
+G2	O
+/	O
+M	O
+-	O
+phase	O
+cells	O
+(	O
+Figure	O
+1B	O
+)	O
+,	O
+although	O
+no	O
+significant	O
+effect	O
+was	O
+found	O
+at	O
+the	O
+G1	O
+phase	O
+.	O
+
+In	O
+addition	O
+,	O
+depletion	O
+of	O
+HP1	O
+caused	O
+a	O
+greater	O
+than	O
+7	O
+-	O
+fold	O
+increase	O
+in	O
+the	O
+number	O
+of	O
+apoptotic	O
+cells	O
+.	O
+
+These	O
+results	O
+,	O
+therefore	O
+,	O
+confirm	O
+that	O
+HP1	O
+is	O
+an	O
+important	O
+regulator	O
+during	O
+the	O
+cell	O
+cycle	O
+,	O
+especially	O
+at	O
+the	O
+S	O
+and	O
+G2	O
+/	O
+M	O
+phases	O
+.	O
+
+Cell	O
+-	O
+cycle	O
+regulators	O
+require	O
+HP1	O
+to	O
+maintain	O
+their	O
+active	O
+transcription	O
+
+To	O
+ask	O
+whether	O
+the	O
+cell	O
+-	O
+cycle	O
+defects	O
+were	O
+due	O
+to	O
+changes	O
+in	O
+the	O
+transcription	O
+of	O
+genes	O
+functionally	O
+involved	O
+in	O
+S	O
+phase	O
+and	O
+the	O
+G2	O
+/	O
+M	O
+phase	O
+,	O
+we	O
+next	O
+assessed	O
+global	O
+changes	O
+in	O
+gene	O
+transcription	O
+following	O
+depletion	O
+of	O
+HP1	O
+.	O
+
+Expression	O
+profile	O
+analysis	O
+was	O
+performed	O
+using	O
+total	O
+RNA	O
+isolated	O
+from	O
+both	O
+HP1	O
+-	O
+depleted	O
+Kc	O
+cells	O
+and	O
+control	O
+Kc	O
+cells	O
+,	O
+and	O
+an	O
+Affymetrix	O
+Drosophila	B
+chip	O
+.	O
+
+For	O
+each	O
+experiment	O
+,	O
+we	O
+used	O
+total	O
+RNA	O
+isolated	O
+from	O
+two	O
+independent	O
+HP1	O
+-	O
+depleted	O
+and	O
+control	O
+samples	O
+,	O
+and	O
+at	O
+least	O
+two	O
+independent	O
+experiments	O
+were	O
+performed	O
+.	O
+
+The	O
+microarray	O
+analysis	O
+showed	O
+that	O
+loss	O
+of	O
+HP1	O
+function	O
+in	O
+Kc	O
+cells	O
+resulted	O
+in	O
+alterations	O
+in	O
+transcription	O
+of	O
+>	O
+500	O
+genes	O
+:	O
+~	O
+400	O
+genes	O
+were	O
+down	O
+-	O
+regulated	O
+and	O
+~	O
+120	O
+genes	O
+were	O
+up	O
+-	O
+regulated	O
+(	O
+>	O
+1	O
+.	O
+5	O
+-	O
+fold	O
+,	O
+ANOVA	O
+)	O
+.	O
+
+The	O
+function	O
+of	O
+these	O
+genes	O
+ranged	O
+from	O
+cellular	O
+enzymes	O
+,	O
+signal	O
+transduction	O
+molecules	O
+,	O
+and	O
+membrane	O
+and	O
+cell	O
+structural	O
+proteins	O
+,	O
+to	O
+nucleic	O
+acid	O
+-	O
+binding	O
+proteins	O
+and	O
+cell	O
+-	O
+cycle	O
+regulators	O
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+At	O
+the	O
+chromosomal	O
+level	O
+,	O
+the	O
+genes	O
+targeted	O
+by	O
+HP1	O
+appeared	O
+to	O
+be	O
+distributed	O
+along	O
+all	O
+euchromatic	O
+chromosomal	O
+arms	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+supporting	O
+a	O
+global	O
+role	O
+of	O
+HP1	O
+in	O
+euchromatic	O
+gene	O
+regulation	O
+(	O
+20	O
+)	O
+.	O
+
+Among	O
+60	O
+known	O
+/	O
+predicted	O
+genes	O
+associated	O
+with	O
+DNA	O
+replication	O
+function	O
+,	O
+15	O
+were	O
+down	O
+-	O
+regulated	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+These	O
+included	O
+McM2	O
+,	O
+McM5	O
+,	O
+McM6	O
+and	O
+CDC45L	O
+,	O
+which	O
+are	O
+required	O
+for	O
+processive	O
+DNA	O
+replication	O
+and	O
+correct	O
+chromosome	O
+condensation	O
+(	O
+30	O
+-	O
+32	O
+)	O
+.	O
+
+Other	O
+genes	O
+involved	O
+in	O
+DNA	O
+replication	O
+,	O
+such	O
+as	O
+components	O
+of	O
+the	O
+origin	O
+recognition	O
+complex	O
+(	O
+Orc	O
+)	O
+-	O
+-	O
+Orc4	O
+,	O
+Caf1	O
+,	O
+Gnf1	O
+,	O
+Dref1	O
+,	O
+DNA	O
+polymerase	O
+-	O
+gamma	O
+and	O
+Tam	O
+-	O
+-	O
+were	O
+also	O
+down	O
+-	O
+regulated	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+Aurora	O
+B	O
+and	O
+inner	O
+centromere	O
+protein	O
+(	O
+INCENP	O
+)	O
+,	O
+known	O
+to	O
+be	O
+required	O
+for	O
+kinetochore	O
+assembly	O
+,	O
+chromosome	O
+condensation	O
+and	O
+bipolar	O
+chromosome	O
+attachment	O
+during	O
+mitosis	O
+(	O
+33	O
+)	O
+,	O
+also	O
+showed	O
+a	O
+reduction	O
+in	O
+transcription	O
+.	O
+
+A	O
+similar	O
+loss	O
+of	O
+transcription	O
+was	O
+observed	O
+in	O
+Bub1	O
+and	O
+Bub3	O
+(	O
+Figure	O
+2B	O
+)	O
+,	O
+encoding	O
+mitotic	O
+checkpoint	O
+control	O
+proteins	O
+(	O
+34	O
+,	O
+35	O
+)	O
+.	O
+
+Loss	O
+function	O
+of	O
+Bub1	O
+has	O
+been	O
+shown	O
+to	O
+cause	O
+chromatin	O
+bridges	O
+to	O
+extend	O
+between	O
+the	O
+two	O
+separating	O
+groups	O
+of	O
+chromosomes	O
+,	O
+and	O
+extensive	O
+chromosome	O
+fragmentation	O
+in	O
+anaphase	O
+cells	O
+(	O
+35	O
+)	O
+.	O
+
+We	O
+confirmed	O
+the	O
+changes	O
+in	O
+the	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulators	O
+using	O
+semi	O
+-	O
+quantitative	O
+RT	O
+-	O
+PCR	O
+,	O
+which	O
+gave	O
+results	O
+consistent	O
+with	O
+the	O
+microarray	O
+analysis	O
+.	O
+
+In	O
+addition	O
+,	O
+cell	O
+-	O
+cycle	O
+regulator	O
+genes	O
+,	O
+such	O
+as	O
+McM3	O
+,	O
+McM7	O
+and	O
+Asp	O
+(	O
+abnormal	O
+spindle	O
+)	O
+,	O
+were	O
+also	O
+confirmed	O
+to	O
+be	O
+down	O
+-	O
+regulated	O
+(	O
+Figure	O
+2C	O
+)	O
+.	O
+
+Collectively	O
+,	O
+these	O
+results	O
+demonstrate	O
+that	O
+HP1	O
+is	O
+indeed	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulators	O
+.	O
+
+HP1	O
+is	O
+required	O
+for	O
+Aurora	O
+B	O
+distribution	O
+and	O
+histone	O
+H3	O
+phosphorylation	O
+
+INCENP	O
+is	O
+localized	O
+to	O
+the	O
+centromeric	O
+region	O
+of	O
+chromosomes	O
+at	O
+metaphase	O
+and	O
+the	O
+spindle	O
+midzone	O
+at	O
+anaphase	O
+,	O
+which	O
+then	O
+targets	O
+Aurora	O
+B	O
+,	O
+a	O
+kinase	O
+essential	O
+for	O
+histone	O
+H3	O
+ser10	O
+phosphorylation	O
+,	O
+to	O
+these	O
+sites	O
+(	O
+36	O
+)	O
+.	O
+
+Loss	O
+of	O
+function	O
+of	O
+both	O
+these	O
+'	O
+chromosomal	O
+passenger	O
+'	O
+proteins	O
+causes	O
+abnormal	O
+chromosomal	O
+segregation	O
+at	O
+metaphase	O
+,	O
+as	O
+well	O
+as	O
+certain	O
+cytokinesis	O
+defects	O
+(	O
+36	O
+,	O
+37	O
+)	O
+.	O
+
+The	O
+loss	O
+of	O
+transcription	O
+of	O
+both	O
+INCENP	O
+and	O
+Aurora	O
+B	O
+after	O
+depletion	O
+of	O
+HP1	O
+,	O
+therefore	O
+,	O
+raised	O
+the	O
+possibility	O
+that	O
+localization	O
+of	O
+Aurora	O
+B	O
+(	O
+Figure	O
+3	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+may	O
+be	O
+altered	O
+.	O
+
+Staining	O
+of	O
+HP1	O
+-	O
+depleted	O
+Kc	O
+cells	O
+with	O
+anti	O
+-	O
+Aurora	O
+B	O
+antibodies	O
+indeed	O
+revealed	O
+an	O
+altered	O
+localization	O
+of	O
+Aurora	O
+B	O
+and	O
+,	O
+in	O
+a	O
+number	O
+of	O
+cases	O
+,	O
+a	O
+complete	O
+loss	O
+of	O
+Aurora	O
+B	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+Consistent	O
+with	O
+the	O
+loss	O
+function	O
+of	O
+Aurora	O
+B	O
+,	O
+the	O
+spindles	O
+in	O
+the	O
+metaphase	O
+cells	O
+were	O
+also	O
+disorganized	O
+,	O
+with	O
+a	O
+large	O
+number	O
+of	O
+cells	O
+showing	O
+an	O
+altered	O
+prometaphase	O
+chromosome	O
+alignment	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+Some	O
+showed	O
+extensive	O
+chromosome	O
+fragmentation	O
+(	O
+Figure	O
+3B	O
+)	O
+,	O
+or	O
+the	O
+presence	O
+of	O
+a	O
+third	O
+spindle	O
+pole	O
+-	O
+like	O
+structure	O
+as	O
+indicated	O
+by	O
+beta	O
+-	O
+tubulin	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+At	O
+telophase	O
+,	O
+we	O
+observed	O
+defective	O
+separating	O
+cells	O
+with	O
+an	O
+extra	O
+cell	O
+envelope	O
+-	O
+like	O
+structure	O
+without	O
+nuclei	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+Chromatin	O
+bridges	O
+or	O
+lagging	O
+chromatids	O
+at	O
+telophase	O
+were	O
+also	O
+evident	O
+in	O
+some	O
+cells	O
+(	O
+Figure	O
+3C	O
+)	O
+;	O
+however	O
+,	O
+in	O
+some	O
+cases	O
+,	O
+localization	O
+of	O
+Aurora	O
+B	O
+appeared	O
+not	O
+to	O
+be	O
+affected	O
+,	O
+arguing	O
+that	O
+other	O
+pathways	O
+are	O
+possibly	O
+involved	O
+.	O
+
+We	O
+next	O
+analyzed	O
+changes	O
+in	O
+histone	O
+H3	O
+serine	O
+10	O
+phosphorylation	O
+,	O
+since	O
+the	O
+loss	O
+of	O
+transcription	O
+of	O
+INCENP	O
+is	O
+known	O
+to	O
+affect	O
+localization	O
+of	O
+Aurora	O
+B	O
+(	O
+33	O
+)	O
+,	O
+which	O
+is	O
+essential	O
+in	O
+the	O
+regulation	O
+of	O
+histone	O
+H3	O
+phosphorylation	O
+(	O
+36	O
+)	O
+.	O
+
+Total	O
+cell	O
+extracts	O
+from	O
+HP1	O
+-	O
+depleted	O
+Kc	O
+cells	O
+were	O
+analyzed	O
+by	O
+western	O
+blotting	O
+(	O
+Figure	O
+3D	O
+)	O
+.	O
+
+The	O
+results	O
+indeed	O
+showed	O
+a	O
+severalfold	O
+reduction	O
+in	O
+H3	O
+ser10	O
+phosphorylation	O
+after	O
+depletion	O
+of	O
+HP1	O
+,	O
+consistent	O
+with	O
+the	O
+functional	O
+disruption	O
+of	O
+INCENP	O
+and	O
+Aurora	O
+B	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+.	O
+
+HP1	O
+directly	O
+targets	O
+genes	O
+encoding	O
+cell	O
+-	O
+cycle	O
+regulators	O
+in	O
+euchromatin	O
+
+To	O
+test	O
+whether	O
+the	O
+loss	O
+of	O
+transcription	O
+of	O
+genes	O
+involved	O
+in	O
+DNA	O
+replication	O
+and	O
+mitosis	O
+was	O
+a	O
+direct	O
+effect	O
+of	O
+the	O
+loss	O
+of	O
+HP1	O
+,	O
+we	O
+performed	O
+a	O
+ChIP	O
+analysis	O
+to	O
+determine	O
+whether	O
+HP1	O
+is	O
+physically	O
+associated	O
+with	O
+these	O
+genes	O
+.	O
+
+Chromatin	O
+lysates	O
+from	O
+formaldehyde	O
+-	O
+fixed	O
+Kc	O
+cells	O
+were	O
+sonicated	O
+into	O
+small	O
+chromatin	O
+fragments	O
+(	O
+0	O
+.	O
+2	O
+-	O
+0	O
+.	O
+8	O
+kb	O
+)	O
+and	O
+immunoprecipitated	O
+with	O
+polyclonal	O
+antibodies	O
+against	O
+Drosophila	B
+HP1	O
+.	O
+
+As	O
+a	O
+control	O
+,	O
+we	O
+used	O
+a	O
+mock	O
+precipitation	O
+(	O
+beads	O
+only	O
+)	O
+and	O
+polyclonal	O
+antibodies	O
+against	O
+HA	O
+.	O
+
+Our	O
+ChIP	O
+results	O
+showed	O
+that	O
+known	O
+transposable	O
+elements	O
+distributed	O
+in	O
+heterochromatin	O
+,	O
+such	O
+as	O
+F	O
+-	O
+element	O
+,	O
+TART	O
+and	O
+1360	O
+(	O
+7	O
+,	O
+38	O
+)	O
+,	O
+were	O
+all	O
+enriched	O
+in	O
+HP1	O
+binding	O
+(	O
+Figure	O
+4	O
+)	O
+,	O
+which	O
+is	O
+also	O
+consistent	O
+with	O
+a	O
+previous	O
+study	O
+(	O
+20	O
+)	O
+.	O
+
+Using	O
+the	O
+same	O
+ChIP	O
+DNA	O
+material	O
+,	O
+we	O
+then	O
+attempted	O
+to	O
+determine	O
+whether	O
+HP1	O
+was	O
+enriched	O
+in	O
+genes	O
+involved	O
+in	O
+DNA	O
+replication	O
+.	O
+
+Primers	O
+were	O
+designed	O
+to	O
+cover	O
+the	O
+promoter	O
+regions	O
+of	O
+selected	O
+genes	O
+.	O
+
+The	O
+results	O
+showed	O
+that	O
+McM3	O
+,	O
+McM5	O
+and	O
+Tam	O
+were	O
+all	O
+enriched	O
+in	O
+HP1	O
+binding	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+However	O
+,	O
+McM7	O
+appeared	O
+to	O
+be	O
+HP1	O
+-	O
+negative	O
+,	O
+although	O
+its	O
+transcription	O
+was	O
+also	O
+affected	O
+by	O
+the	O
+loss	O
+of	O
+HP1	O
+function	O
+.	O
+
+Genes	O
+essential	O
+for	O
+mitosis	O
+,	O
+such	O
+as	O
+Aurora	O
+B	O
+,	O
+were	O
+also	O
+HP1	O
+-	O
+positive	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+these	O
+cell	O
+-	O
+cycle	O
+regulator	O
+genes	O
+are	O
+directly	O
+targeted	O
+by	O
+HP1	O
+in	O
+their	O
+promoter	O
+regions	O
+.	O
+
+DISCUSSION	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+used	O
+microarray	O
+and	O
+RT	O
+-	O
+PCR	O
+techniques	O
+to	O
+demonstrate	O
+that	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulators	O
+is	O
+misregulated	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+.	O
+
+Certain	O
+defects	O
+in	O
+S	O
+phase	O
+may	O
+be	O
+a	O
+direct	O
+consequence	O
+of	O
+the	O
+loss	O
+of	O
+transcription	O
+of	O
+DNA	O
+replication	O
+genes	O
+such	O
+as	O
+McM2	O
+,	O
+McM5	O
+,	O
+McM6	O
+,	O
+CDC45L	O
+,	O
+Orc4	O
+and	O
+others	O
+,	O
+since	O
+these	O
+genes	O
+have	O
+been	O
+functionally	O
+implicated	O
+in	O
+the	O
+initiation	O
+of	O
+DNA	O
+replication	O
+and	O
+/	O
+or	O
+the	O
+progression	O
+of	O
+replication	O
+forks	O
+(	O
+39	O
+)	O
+.	O
+
+Depletion	O
+or	O
+mutation	O
+of	O
+these	O
+genes	O
+has	O
+been	O
+shown	O
+to	O
+result	O
+in	O
+DNA	O
+damage	O
+(	O
+32	O
+)	O
+,	O
+the	O
+blockage	O
+of	O
+replication	O
+forks	O
+(	O
+39	O
+)	O
+,	O
+increased	O
+chromosome	O
+loss	O
+/	O
+genome	O
+instability	O
+,	O
+and	O
+defective	O
+condensation	O
+(	O
+30	O
+)	O
+.	O
+
+The	O
+reduction	O
+in	O
+the	O
+number	O
+of	O
+cells	O
+in	O
+G2	O
+/	O
+M	O
+phase	O
+may	O
+be	O
+a	O
+consequence	O
+of	O
+the	O
+reduction	O
+in	O
+transcription	O
+or	O
+functional	O
+disruption	O
+of	O
+INCENP	O
+,	O
+Aurora	O
+B	O
+,	O
+Bub1	O
+,	O
+and	O
+Bub3	O
+(	O
+34	O
+,	O
+36	O
+)	O
+.	O
+
+Chromosome	O
+segregation	O
+defects	O
+,	O
+such	O
+as	O
+chromosome	O
+fragmentation	O
+and	O
+chromatin	O
+bridges	O
+in	O
+anaphase	O
+/	O
+telophase	O
+cells	O
+,	O
+and	O
+certain	O
+cytokinesis	O
+defects	O
+in	O
+HP1	O
+-	O
+depleted	O
+cells	O
+,	O
+mimic	O
+the	O
+phenotype	O
+of	O
+cells	O
+with	O
+loss	O
+function	O
+of	O
+INCENP	O
+,	O
+Aurora	O
+B	O
+or	O
+Bub1	O
+(	O
+35	O
+-	O
+37	O
+)	O
+.	O
+
+The	O
+mislocalization	O
+of	O
+Aurora	O
+B	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+is	O
+also	O
+consistent	O
+with	O
+the	O
+loss	O
+of	O
+transcription	O
+and	O
+functional	O
+disruption	O
+of	O
+INCENP	O
+(	O
+37	O
+)	O
+,	O
+and	O
+the	O
+reduction	O
+in	O
+Aurora	O
+B	O
+transcription	O
+may	O
+be	O
+partially	O
+responsible	O
+for	O
+the	O
+observed	O
+chromosomal	O
+defects	O
+,	O
+including	O
+loss	O
+of	O
+histone	O
+H3	O
+phosphorylation	O
+at	O
+serine	O
+10	O
+.	O
+
+HP1	O
+is	O
+also	O
+known	O
+to	O
+physically	O
+interact	O
+with	O
+certain	O
+components	O
+of	O
+replication	O
+complexes	O
+such	O
+as	O
+ORCs	O
+and	O
+MCMs	O
+(	O
+30	O
+,	O
+40	O
+,	O
+41	O
+)	O
+,	O
+with	O
+the	O
+inner	O
+centromere	O
+protein	O
+INCENP	O
+(	O
+42	O
+)	O
+and	O
+the	O
+chromatin	O
+assembly	O
+factor	O
+CAF1	O
+(	O
+43	O
+)	O
+promoting	O
+delivery	O
+of	O
+HP1	O
+to	O
+heterochromatin	O
+sites	O
+(	O
+44	O
+)	O
+.	O
+
+Loss	O
+of	O
+HP1	O
+is	O
+,	O
+therefore	O
+,	O
+expected	O
+to	O
+cause	O
+disruption	O
+to	O
+such	O
+HP1	O
+-	O
+associated	O
+complexes	O
+,	O
+and	O
+will	O
+partially	O
+contribute	O
+to	O
+the	O
+chromatin	O
+/	O
+chromosomal	O
+defects	O
+in	O
+HP1	O
+mutants	O
+(	O
+8	O
+,	O
+27	O
+)	O
+and	O
+HP1	O
+-	O
+depleted	O
+Kc	O
+cells	O
+.	O
+
+It	O
+is	O
+therefore	O
+well	O
+possible	O
+that	O
+the	O
+loss	O
+of	O
+transcription	O
+of	O
+these	O
+cell	O
+-	O
+cycle	O
+regulator	O
+genes	O
+,	O
+and	O
+consequent	O
+disruption	O
+of	O
+HP1	O
+functional	O
+complexes	O
+or	O
+heterochromatin	O
+structure	O
+,	O
+all	O
+contributed	O
+to	O
+the	O
+cell	O
+-	O
+cycle	O
+defects	O
+observed	O
+.	O
+
+The	O
+ChIP	O
+assay	O
+supports	O
+the	O
+hypothesis	O
+that	O
+the	O
+loss	O
+of	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulator	O
+genes	O
+is	O
+a	O
+direct	O
+effect	O
+of	O
+the	O
+lack	O
+of	O
+HP1	O
+.	O
+
+Aurora	O
+B	O
+,	O
+McM3	O
+,	O
+and	O
+McM5	O
+were	O
+all	O
+bound	O
+by	O
+HP1	O
+at	O
+their	O
+promoter	O
+regions	O
+,	O
+although	O
+other	O
+cell	O
+-	O
+cycle	O
+regulators	O
+,	O
+such	O
+as	O
+McM7	O
+,	O
+were	O
+HP1	O
+-	O
+negative	O
+,	O
+implying	O
+that	O
+the	O
+altered	O
+transcription	O
+in	O
+these	O
+genes	O
+might	O
+be	O
+a	O
+secondary	O
+effect	O
+of	O
+the	O
+loss	O
+of	O
+HP1	O
+.	O
+
+A	O
+previous	O
+study	O
+in	O
+Drosophila	B
+Kc	O
+cells	O
+(	O
+20	O
+)	O
+employed	O
+an	O
+approach	O
+based	O
+on	O
+the	O
+ectopic	O
+expression	O
+of	O
+a	O
+fusion	O
+protein	O
+of	O
+HP1	O
+with	O
+a	O
+prokaryotic	O
+DNA	O
+adenine	O
+methyltransferase	O
+and	O
+identified	O
+a	O
+number	O
+of	O
+methylated	O
+targets	O
+in	O
+the	O
+genome	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+MCM3	O
+and	O
+MCM5	O
+were	O
+not	O
+found	O
+to	O
+be	O
+methylated	O
+,	O
+indicating	O
+lack	O
+of	O
+association	O
+with	O
+HP1	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+heterochromatin	O
+repeats	O
+,	O
+such	O
+F	O
+-	O
+element	O
+and	O
+1360	O
+,	O
+were	O
+consistently	O
+found	O
+to	O
+be	O
+HP1	O
+-	O
+enriched	O
+both	O
+here	O
+and	O
+in	O
+the	O
+previous	O
+study	O
+.	O
+
+It	O
+remains	O
+to	O
+be	O
+determined	O
+whether	O
+these	O
+discrepancies	O
+are	O
+due	O
+to	O
+the	O
+different	O
+experimental	O
+systems	O
+used	O
+.	O
+
+However	O
+,	O
+we	O
+note	O
+that	O
+the	O
+previous	O
+study	O
+was	O
+performed	O
+using	O
+a	O
+cDNA	O
+array	O
+,	O
+while	O
+we	O
+observe	O
+binding	O
+of	O
+endogenous	O
+HP1	O
+at	O
+the	O
+promoter	O
+of	O
+these	O
+genes	O
+.	O
+
+Similarly	O
+,	O
+another	O
+study	O
+using	O
+chromatin	O
+immunoprecipitation	O
+in	O
+larvae	O
+also	O
+showed	O
+few	O
+HP1	O
+-	O
+positive	O
+genes	O
+that	O
+were	O
+not	O
+detected	O
+in	O
+Kc	O
+cells	O
+by	O
+the	O
+Dam	O
+ID	O
+approach	O
+(	O
+21	O
+)	O
+.	O
+
+A	O
+large	O
+number	O
+of	O
+genes	O
+affected	O
+by	O
+the	O
+loss	O
+of	O
+D	B
+.	I
+melanogaster	I
+HP1	O
+in	O
+larval	O
+tissues	O
+(	O
+21	O
+)	O
+seem	O
+to	O
+be	O
+different	O
+from	O
+that	O
+in	O
+embryonic	O
+Kc	O
+cells	O
+.	O
+
+The	O
+change	O
+in	O
+the	O
+transcription	O
+of	O
+Aurora	O
+B	O
+and	O
+few	O
+cell	O
+-	O
+cycle	O
+regulators	O
+reported	O
+in	O
+this	O
+study	O
+is	O
+also	O
+not	O
+found	O
+among	O
+the	O
+HP1	O
+-	O
+affected	O
+genes	O
+at	O
+larval	O
+stage	O
+(	O
+21	O
+)	O
+.	O
+
+This	O
+may	O
+be	O
+due	O
+to	O
+specific	O
+role	O
+(	O
+s	O
+)	O
+of	O
+HP1	O
+in	O
+different	O
+stages	O
+of	O
+development	O
+.	O
+
+Alternatively	O
+,	O
+it	O
+is	O
+also	O
+possible	O
+that	O
+the	O
+impact	O
+of	O
+HP1	O
+in	O
+the	O
+transcription	O
+of	O
+cell	O
+-	O
+cycle	O
+regulators	O
+in	O
+proliferating	O
+cells	O
+is	O
+underestimated	O
+when	O
+performing	O
+the	O
+analyses	O
+on	O
+larval	O
+tissues	O
+,	O
+and	O
+thus	O
+on	O
+mixed	O
+populations	O
+of	O
+both	O
+proliferating	O
+and	O
+differentiating	O
+/	O
+differentiated	O
+cells	O
+.	O
+
+HP1	O
+is	O
+generally	O
+known	O
+as	O
+a	O
+transcriptional	O
+repressor	O
+,	O
+as	O
+supported	O
+by	O
+several	O
+lines	O
+of	O
+evidence	O
+:	O
+silencing	O
+of	O
+a	O
+euchromatic	O
+reporter	O
+gene	O
+in	O
+heterochromatin	O
+requires	O
+HP1	O
+(	O
+10	O
+,	O
+11	O
+)	O
+,	O
+tethering	O
+of	O
+HP1	O
+next	O
+to	O
+a	O
+euchromatic	O
+reporter	O
+gene	O
+causes	O
+silencing	O
+(	O
+45	O
+)	O
+,	O
+and	O
+the	O
+repression	O
+of	O
+genes	O
+within	O
+euchromatic	O
+region	O
+31	O
+bound	O
+by	O
+HP1	O
+is	O
+relieved	O
+in	O
+the	O
+absence	O
+of	O
+HP1	O
+(	O
+46	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+genes	O
+in	O
+heterochromatin	O
+,	O
+known	O
+as	O
+heterochromatic	O
+genes	O
+,	O
+such	O
+as	O
+light	O
+and	O
+rolled	O
+,	O
+seem	O
+to	O
+require	O
+HP1	O
+to	O
+maintain	O
+their	O
+active	O
+transcription	O
+(	O
+47	O
+,	O
+48	O
+)	O
+.	O
+
+The	O
+level	O
+of	O
+transcription	O
+of	O
+heterochromatic	O
+genes	O
+was	O
+dramatically	O
+reduced	O
+in	O
+a	O
+mutated	O
+HP1	O
+background	O
+(	O
+47	O
+-	O
+49	O
+)	O
+.	O
+
+It	O
+was	O
+therefore	O
+proposed	O
+that	O
+HP1	O
+may	O
+function	O
+as	O
+a	O
+positive	O
+regulator	O
+of	O
+transcription	O
+of	O
+these	O
+genes	O
+(	O
+50	O
+,	O
+51	O
+)	O
+,	O
+although	O
+the	O
+exact	O
+regulation	O
+mechanism	O
+remains	O
+unclear	O
+.	O
+
+A	O
+study	O
+of	O
+heat	O
+-	O
+shock	O
+genes	O
+found	O
+that	O
+HP1	O
+is	O
+associated	O
+with	O
+RNA	O
+transcripts	O
+in	O
+the	O
+coding	O
+region	O
+,	O
+and	O
+is	O
+also	O
+a	O
+positive	O
+regulator	O
+of	O
+their	O
+transcription	O
+(	O
+52	O
+,	O
+53	O
+)	O
+.	O
+
+The	O
+chromatin	O
+association	O
+of	O
+HP1	O
+at	O
+the	O
+promoter	O
+region	O
+of	O
+active	O
+euchromatic	O
+genes	O
+demonstrated	O
+from	O
+this	O
+work	O
+and	O
+others	O
+,	O
+and	O
+its	O
+independence	O
+from	O
+histone	O
+H3K9	O
+methylation	O
+(	O
+21	O
+)	O
+,	O
+all	O
+suggest	O
+that	O
+mechanism	O
+whereby	O
+HP1	O
+modulates	O
+transcription	O
+of	O
+euchromatic	O
+genes	O
+is	O
+potentially	O
+distinct	O
+from	O
+its	O
+role	O
+in	O
+heterochromatin	O
+formation	O
+.	O
+
+Collectively	O
+,	O
+the	O
+results	O
+of	O
+this	O
+study	O
+demonstrate	O
+that	O
+HP1	O
+plays	O
+an	O
+essential	O
+role	O
+in	O
+cell	O
+-	O
+cycle	O
+progression	O
+,	O
+and	O
+support	O
+the	O
+view	O
+that	O
+HP1	O
+,	O
+in	O
+addition	O
+to	O
+its	O
+role	O
+in	O
+heterochromatin	O
+,	O
+can	O
+act	O
+as	O
+a	O
+positive	O
+transcriptional	O
+regulator	O
+of	O
+euchromatic	O
+genes	O
+.	O
+
+SUPPLEMENTARY	O
+MATERIAL	O
+
+Supplementary	O
+Material	O
+is	O
+available	O
+at	O
+NAR	O
+Online	O
+.	O
+
+Supplementary	O
+Material	O
+
+Structural	O
+organization	O
+and	O
+interactions	O
+of	O
+transmembrane	O
+domains	O
+in	O
+tetraspanin	O
+proteins	O
+
+Abstract	O
+
+Background	O
+
+Proteins	O
+of	O
+the	O
+tetraspanin	O
+family	O
+contain	O
+four	O
+transmembrane	O
+domains	O
+(	O
+TM1	O
+-	O
+4	O
+)	O
+linked	O
+by	O
+two	O
+extracellular	O
+loops	O
+and	O
+a	O
+short	O
+intracellular	O
+loop	O
+,	O
+and	O
+have	O
+short	O
+intracellular	O
+N	O
+-	O
+and	O
+C	O
+-	O
+termini	O
+.	O
+
+While	O
+structure	O
+and	O
+function	O
+analysis	O
+of	O
+the	O
+larger	O
+extracellular	O
+loop	O
+has	O
+been	O
+performed	O
+,	O
+the	O
+organization	O
+and	O
+role	O
+of	O
+transmembrane	O
+domains	O
+have	O
+not	O
+been	O
+systematically	O
+assessed	O
+.	O
+
+Results	O
+
+Among	O
+28	O
+human	B
+tetraspanin	O
+proteins	O
+,	O
+the	O
+TM1	O
+-	O
+3	O
+sequences	O
+display	O
+a	O
+distinct	O
+heptad	O
+repeat	O
+motif	O
+(	O
+abcdefg	O
+)	O
+n	O
+.	O
+
+In	O
+TM1	O
+,	O
+position	O
+a	O
+is	O
+occupied	O
+by	O
+structurally	O
+conserved	O
+bulky	O
+residues	O
+and	O
+position	O
+d	O
+contains	O
+highly	O
+conserved	O
+Asn	O
+and	O
+Gly	O
+residues	O
+.	O
+
+In	O
+TM2	O
+,	O
+position	O
+a	O
+is	O
+occupied	O
+by	O
+conserved	O
+small	O
+residues	O
+(	O
+Gly	O
+/	O
+Ala	O
+/	O
+Thr	O
+)	O
+,	O
+and	O
+position	O
+d	O
+has	O
+a	O
+conserved	O
+Gly	O
+and	O
+two	O
+bulky	O
+aliphatic	O
+residues	O
+.	O
+
+In	O
+TM3	O
+,	O
+three	O
+a	O
+positions	O
+of	O
+the	O
+heptad	O
+repeat	O
+are	O
+filled	O
+by	O
+two	O
+leucines	O
+and	O
+a	O
+glutamate	O
+/	O
+glutamine	O
+residue	O
+,	O
+and	O
+two	O
+d	O
+positions	O
+are	O
+occupied	O
+by	O
+either	O
+Phe	O
+/	O
+Tyr	O
+or	O
+Val	O
+/	O
+Ile	O
+/	O
+Leu	O
+residues	O
+.	O
+
+No	O
+heptad	O
+motif	O
+is	O
+apparent	O
+in	O
+TM4	O
+sequences	O
+.	O
+
+Mutations	O
+of	O
+conserved	O
+glycines	O
+in	O
+human	B
+CD9	O
+(	O
+Gly25	O
+and	O
+Gly32	O
+in	O
+TM1	O
+;	O
+Gly67	O
+and	O
+Gly74	O
+in	O
+TM2	O
+)	O
+caused	O
+aggregation	O
+of	O
+mutant	O
+proteins	O
+inside	O
+the	O
+cell	O
+.	O
+
+Modeling	O
+of	O
+the	O
+TM1	O
+-	O
+TM2	O
+interface	O
+in	O
+CD9	O
+,	O
+using	O
+a	O
+novel	O
+algorithm	O
+,	O
+predicts	O
+tight	O
+packing	O
+of	O
+conserved	O
+bulky	O
+residues	O
+against	O
+conserved	O
+Gly	O
+residues	O
+along	O
+the	O
+two	O
+helices	O
+.	O
+
+The	O
+homodimeric	O
+interface	O
+of	O
+CD9	O
+was	O
+mapped	O
+,	O
+by	O
+disulfide	O
+cross	O
+-	O
+linking	O
+of	O
+single	O
+-	O
+cysteine	O
+mutants	O
+,	O
+to	O
+the	O
+vicinity	O
+of	O
+residues	O
+Leu14	O
+and	O
+Phe17	O
+in	O
+TM1	O
+(	O
+positions	O
+g	O
+and	O
+c	O
+)	O
+and	O
+Gly77	O
+,	O
+Gly80	O
+and	O
+Ala81	O
+in	O
+TM2	O
+(	O
+positions	O
+d	O
+,	O
+g	O
+and	O
+a	O
+,	O
+respectively	O
+)	O
+.	O
+
+Mutations	O
+of	O
+a	O
+and	O
+d	O
+residues	O
+in	O
+both	O
+TM1	O
+and	O
+TM2	O
+(	O
+Gly25	O
+,	O
+Gly32	O
+,	O
+Gly67	O
+and	O
+Gly74	O
+)	O
+,	O
+involved	O
+in	O
+intramolecular	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+,	O
+also	O
+strongly	O
+diminished	O
+intermolecular	O
+interaction	O
+,	O
+as	O
+assessed	O
+by	O
+cross	O
+-	O
+linking	O
+of	O
+Cys80	O
+.	O
+
+Conclusion	O
+
+Our	O
+results	O
+suggest	O
+that	O
+tetraspanin	O
+intra	O
+-	O
+and	O
+intermolecular	O
+interactions	O
+are	O
+mediated	O
+by	O
+conserved	O
+residues	O
+in	O
+adjacent	O
+,	O
+but	O
+distinct	O
+regions	O
+of	O
+TM1	O
+and	O
+TM2	O
+.	O
+
+A	O
+key	O
+structural	O
+element	O
+that	O
+defines	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+in	O
+tetraspanins	O
+is	O
+the	O
+specific	O
+packing	O
+of	O
+bulky	O
+residues	O
+against	O
+small	O
+residues	O
+.	O
+
+Background	O
+
+Tetraspanins	O
+constitute	O
+a	O
+large	O
+family	O
+of	O
+integral	O
+membrane	O
+proteins	O
+,	O
+characteristically	O
+containing	O
+4	O
+,	O
+6	O
+or	O
+8	O
+conserved	O
+cysteine	O
+residues	O
+in	O
+the	O
+large	O
+extracellular	O
+loop	O
+(	O
+including	O
+the	O
+CCG	O
+and	O
+PxxCC	O
+motifs	O
+)	O
+,	O
+which	O
+form	O
+disulfide	O
+bonds	O
+,	O
+and	O
+several	O
+conserved	O
+polar	O
+residues	O
+in	O
+the	O
+intracellular	O
+loop	O
+and	O
+transmembrane	O
+regions	O
+[	O
+1	O
+,	O
+2	O
+]	O
+.	O
+
+There	O
+are	O
+32	O
+putative	O
+tetraspanin	O
+family	O
+members	O
+in	O
+mammals	O
+,	O
+37	O
+in	O
+Drosophila	B
+melanogaster	I
+and	O
+20	O
+in	O
+Caenorhabditis	B
+elegans	I
+.	O
+
+Tetraspanins	O
+play	O
+diverse	O
+roles	O
+in	O
+cell	O
+adhesion	O
+,	O
+migration	O
+and	O
+fusion	O
+processes	O
+,	O
+cellular	O
+activation	O
+and	O
+signaling	O
+(	O
+reviewed	O
+in	O
+refs	O
+.	O
+[	O
+2	O
+-	O
+4	O
+]	O
+)	O
+.	O
+
+Mammalian	O
+tetraspanins	O
+such	O
+as	O
+CD9	O
+,	O
+CD63	O
+,	O
+CD81	O
+,	O
+CD82	O
+,	O
+CD151	O
+,	O
+rds	O
+/	O
+peripherin	O
+,	O
+and	O
+uroplakins	O
+Ia	O
+and	O
+Ib	O
+have	O
+been	O
+most	O
+extensively	O
+studied	O
+,	O
+with	O
+mouse	B
+knock	O
+-	O
+out	O
+models	O
+available	O
+for	O
+CD9	O
+[	O
+5	O
+-	O
+7	O
+]	O
+,	O
+CD81	O
+[	O
+8	O
+,	O
+9	O
+]	O
+,	O
+CD151	O
+[	O
+10	O
+]	O
+and	O
+a	O
+few	O
+others	O
+.	O
+
+However	O
+,	O
+the	O
+majority	O
+of	O
+tetraspanins	O
+are	O
+characterized	O
+very	O
+little	O
+,	O
+if	O
+at	O
+all	O
+,	O
+at	O
+genetic	O
+,	O
+biochemical	O
+or	O
+structural	O
+levels	O
+.	O
+
+The	O
+large	O
+extracellular	O
+loop	O
+(	O
+LEL	O
+)	O
+of	O
+tetraspanins	O
+has	O
+received	O
+most	O
+attention	O
+,	O
+since	O
+it	O
+contains	O
+functionally	O
+important	O
+sites	O
+.	O
+
+Sequence	O
+QRD	O
+(	O
+194	O
+-	O
+196	O
+)	O
+in	O
+CD151	O
+is	O
+important	O
+for	O
+association	O
+with	O
+integrins	O
+,	O
+which	O
+has	O
+functional	O
+consequences	O
+for	O
+integrin	O
+-	O
+dependent	O
+cell	O
+spreading	O
+and	O
+multicellular	O
+cable	O
+formation	O
+[	O
+11	O
+]	O
+.	O
+
+A	O
+site	O
+in	O
+the	O
+LEL	O
+of	O
+CD9	O
+,	O
+SFQ	O
+(	O
+residues	O
+173	O
+-	O
+175	O
+)	O
+,	O
+is	O
+essential	O
+for	O
+CD9	O
+function	O
+in	O
+sperm	O
+-	O
+egg	O
+fusion	O
+[	O
+12	O
+]	O
+.	O
+
+The	O
+crystal	O
+structure	O
+of	O
+tetraspanin	O
+CD81	O
+LEL	O
+revealed	O
+five	O
+alpha	O
+-	O
+helixes	O
+,	O
+A	O
+-	O
+E	O
+[	O
+13	O
+]	O
+.	O
+
+Helices	O
+A	O
+,	O
+B	O
+and	O
+E	O
+form	O
+a	O
+relatively	O
+conserved	O
+region	O
+in	O
+tetraspanins	O
+,	O
+whereas	O
+the	O
+region	O
+between	O
+helices	O
+B	O
+and	O
+E	O
+is	O
+the	O
+most	O
+variable	O
+[	O
+14	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+variable	O
+region	O
+contains	O
+most	O
+of	O
+the	O
+functionally	O
+important	O
+sites	O
+involved	O
+in	O
+tetraspanin	O
+protein	O
+-	O
+protein	O
+interactions	O
+.	O
+
+A	O
+remarkable	O
+biochemical	O
+property	O
+of	O
+tetraspanin	O
+molecules	O
+is	O
+their	O
+ability	O
+to	O
+associate	O
+with	O
+a	O
+large	O
+number	O
+of	O
+other	O
+transmembrane	O
+proteins	O
+,	O
+including	O
+integrins	O
+,	O
+membrane	O
+-	O
+associated	O
+growth	O
+factors	O
+and	O
+receptors	O
+,	O
+MHC	O
+class	O
+II	O
+molecules	O
+,	O
+Ig	O
+superfamily	O
+proteins	O
+,	O
+and	O
+each	O
+other	O
+[	O
+2	O
+,	O
+3	O
+,	O
+15	O
+]	O
+.	O
+
+Several	O
+of	O
+these	O
+lateral	O
+associations	O
+of	O
+tetraspanins	O
+are	O
+detected	O
+in	O
+"	O
+mild	O
+"	O
+detergents	O
+(	O
+Brij	O
+series	O
+,	O
+CHAPS	O
+)	O
+,	O
+but	O
+are	O
+disrupted	O
+by	O
+"	O
+strong	O
+"	O
+detergents	O
+such	O
+as	O
+Triton	O
+X	O
+-	O
+100	O
+or	O
+SDS	O
+.	O
+
+Multiprotein	O
+complexes	O
+of	O
+tetraspanins	O
+and	O
+associated	O
+molecules	O
+,	O
+also	O
+called	O
+the	O
+"	O
+tetraspanin	O
+web	O
+"	O
+[	O
+16	O
+]	O
+,	O
+may	O
+represent	O
+a	O
+distinct	O
+tetraspanin	O
+-	O
+enriched	O
+membrane	O
+microdomain	O
+[	O
+17	O
+,	O
+18	O
+]	O
+.	O
+
+The	O
+formation	O
+of	O
+this	O
+microdomain	O
+is	O
+influenced	O
+by	O
+palmitoylation	O
+of	O
+several	O
+conserved	O
+juxtamembrane	O
+cysteine	O
+residues	O
+in	O
+tetraspanins	O
+[	O
+19	O
+-	O
+21	O
+]	O
+.	O
+
+The	O
+transmembrane	O
+domains	O
+,	O
+encompassing	O
+nearly	O
+half	O
+of	O
+a	O
+tetraspanin	O
+protein	O
+,	O
+are	O
+the	O
+most	O
+conserved	O
+part	O
+of	O
+the	O
+molecule	O
+(	O
+Stipp	O
+et	O
+al	O
+.	O
+[	O
+1	O
+]	O
+and	O
+this	O
+study	O
+)	O
+.	O
+
+However	O
+,	O
+very	O
+little	O
+functional	O
+information	O
+is	O
+available	O
+on	O
+these	O
+domains	O
+.	O
+
+The	O
+differential	O
+detergent	O
+sensitivity	O
+of	O
+tetraspanin	O
+-	O
+tetraspanin	O
+associations	O
+suggests	O
+that	O
+hydrophobic	O
+interactions	O
+between	O
+TM	O
+helices	O
+may	O
+play	O
+a	O
+role	O
+.	O
+
+Indeed	O
+,	O
+when	O
+the	O
+large	O
+extracellular	O
+loop	O
+(	O
+LEL	O
+)	O
+of	O
+CD151	O
+is	O
+deleted	O
+,	O
+the	O
+molecule	O
+is	O
+still	O
+able	O
+to	O
+associate	O
+with	O
+other	O
+tetraspanins	O
+[	O
+22	O
+]	O
+.	O
+
+Thus	O
+,	O
+TM	O
+domains	O
+are	O
+strong	O
+candidates	O
+for	O
+mediating	O
+tetraspanin	O
+-	O
+tetraspanin	O
+interactions	O
+.	O
+
+The	O
+importance	O
+of	O
+TM	O
+domain	O
+interactions	O
+in	O
+intramolecular	O
+organization	O
+was	O
+demonstrated	O
+in	O
+a	O
+study	O
+showing	O
+that	O
+CD82	O
+fragment	O
+TM2	O
+-	O
+4	O
+,	O
+lacking	O
+TM1	O
+,	O
+was	O
+retained	O
+in	O
+the	O
+endoplasmic	O
+reticulum	O
+,	O
+but	O
+was	O
+transported	O
+to	O
+the	O
+cell	O
+surface	O
+upon	O
+co	O
+-	O
+expression	O
+of	O
+TM1	O
+[	O
+23	O
+]	O
+.	O
+
+This	O
+in	O
+vivo	O
+reconstitution	O
+experiment	O
+demonstrated	O
+a	O
+strong	O
+interaction	O
+between	O
+TM1	O
+and	O
+the	O
+rest	O
+of	O
+the	O
+molecule	O
+.	O
+
+Expression	O
+of	O
+a	O
+truncated	O
+CD9	O
+molecule	O
+(	O
+TM3	O
+-	O
+LEL	O
+-	O
+TM4	O
+)	O
+results	O
+in	O
+intracellular	O
+accumulation	O
+of	O
+the	O
+protein	O
+and	O
+significant	O
+misfolding	O
+of	O
+the	O
+LEL	O
+,	O
+as	O
+judged	O
+by	O
+inappropriate	O
+disulfide	O
+formation	O
+and	O
+diminished	O
+antibody	O
+reactivity	O
+(	O
+our	O
+unpublished	O
+data	O
+)	O
+.	O
+
+Similarly	O
+,	O
+a	O
+CD9	O
+epitope	O
+in	O
+the	O
+LEL	O
+is	O
+lost	O
+in	O
+molecules	O
+lacking	O
+either	O
+TM2	O
++	O
+TM3	O
+or	O
+just	O
+TM4	O
+[	O
+24	O
+]	O
+.	O
+
+Thus	O
+,	O
+TM	O
+domain	O
+interactions	O
+and	O
+packing	O
+are	O
+crucial	O
+for	O
+proper	O
+folding	O
+,	O
+stability	O
+and	O
+transport	O
+of	O
+tetraspanin	O
+molecules	O
+.	O
+
+In	O
+a	O
+previous	O
+study	O
+,	O
+we	O
+showed	O
+that	O
+covalent	O
+cross	O
+-	O
+linking	O
+of	O
+membrane	O
+-	O
+proximal	O
+cysteine	O
+residues	O
+can	O
+be	O
+used	O
+as	O
+a	O
+tool	O
+for	O
+detection	O
+of	O
+tetraspanin	O
+-	O
+tetraspanin	O
+associations	O
+[	O
+25	O
+]	O
+.	O
+
+Inhibition	O
+of	O
+cysteine	O
+palmitoylation	O
+by	O
+2	O
+-	O
+bromopalmitate	O
+(	O
+2	O
+-	O
+BP	O
+)	O
+made	O
+cysteines	O
+available	O
+for	O
+cross	O
+-	O
+linking	O
+and	O
+enabled	O
+demonstration	O
+of	O
+specific	O
+tetraspanin	O
+homodimerization	O
+and	O
+low	O
+levels	O
+of	O
+heterodimerization	O
+.	O
+
+We	O
+concluded	O
+that	O
+tetraspanin	O
+homodimers	O
+,	O
+formed	O
+in	O
+the	O
+Golgi	O
+,	O
+may	O
+be	O
+a	O
+fundamental	O
+structural	O
+unit	O
+within	O
+tetraspanin	O
+microdomains	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+carried	O
+out	O
+detailed	O
+sequence	O
+analysis	O
+of	O
+human	B
+tetraspanin	O
+TM	O
+domains	O
+.	O
+
+We	O
+show	O
+that	O
+a	O
+heptad	O
+repeat	O
+containing	O
+conserved	O
+glycine	O
+,	O
+asparagine	O
+and	O
+large	O
+hydrophobic	O
+residues	O
+occurs	O
+in	O
+TM1	O
+and	O
+TM2	O
+domains	O
+,	O
+and	O
+predict	O
+tight	O
+intramolecular	O
+association	O
+of	O
+these	O
+two	O
+domains	O
+by	O
+packing	O
+of	O
+the	O
+large	O
+residues	O
+against	O
+the	O
+small	O
+residues	O
+.	O
+
+Moreover	O
+,	O
+by	O
+using	O
+cysteine	O
+cross	O
+-	O
+linking	O
+we	O
+map	O
+a	O
+dimerization	O
+interface	O
+in	O
+the	O
+human	B
+CD9	O
+protein	O
+,	O
+and	O
+show	O
+that	O
+conserved	O
+heptad	O
+motif	O
+glycine	O
+residues	O
+are	O
+also	O
+important	O
+for	O
+intermolecular	O
+CD9	O
+associations	O
+.	O
+
+Results	O
+
+Sequence	O
+analysis	O
+of	O
+tetraspanin	O
+transmembrane	O
+domains	O
+:	O
+presence	O
+of	O
+the	O
+heptad	O
+repeat	O
+motif	O
+
+We	O
+focused	O
+our	O
+attention	O
+on	O
+28	O
+human	B
+tetraspanins	O
+identified	O
+from	O
+the	O
+SWISS	O
+-	O
+PROT	O
+and	O
+GenBank	O
+databases	O
+.	O
+
+All	O
+tetraspanins	O
+have	O
+in	O
+common	O
+four	O
+hydrophobic	O
+stretches	O
+(	O
+TM	O
+domains	O
+)	O
+of	O
+20	O
+-	O
+25	O
+residues	O
+,	O
+and	O
+contain	O
+highly	O
+conserved	O
+residues	O
+in	O
+the	O
+second	O
+extracellular	O
+loop	O
+,	O
+in	O
+particular	O
+the	O
+Cys	O
+-	O
+Cys	O
+-	O
+Gly	O
+(	O
+CCG	O
+)	O
+motif	O
+.	O
+
+Detailed	O
+analysis	O
+of	O
+the	O
+large	O
+extracellular	O
+loop	O
+sequences	O
+[	O
+14	O
+]	O
+,	O
+and	O
+dendrograms	O
+based	O
+on	O
+full	O
+-	O
+length	O
+alignment	O
+can	O
+be	O
+found	O
+in	O
+earlier	O
+studies	O
+[	O
+26	O
+,	O
+27	O
+]	O
+.	O
+
+The	O
+length	O
+of	O
+each	O
+transmembrane	O
+domain	O
+was	O
+established	O
+based	O
+on	O
+previous	O
+sequence	O
+analysis	O
+of	O
+tetraspanin	O
+sequences	O
+[	O
+27	O
+,	O
+28	O
+]	O
+,	O
+and	O
+on	O
+annotations	O
+to	O
+the	O
+database	O
+entries	O
+.	O
+
+Manual	O
+adjustments	O
+based	O
+on	O
+sequence	O
+homology	O
+and	O
+hydrophobicity	O
+profiles	O
+were	O
+done	O
+to	O
+fully	O
+delineate	O
+the	O
+TM	O
+domains	O
+.	O
+
+The	O
+resulting	O
+lengths	O
+of	O
+TM	O
+domains	O
+were	O
+:	O
+TM1	O
+-	O
+23	O
+residues	O
+;	O
+TM2	O
+-	O
+21	O
+residues	O
+;	O
+TM3	O
+-	O
+25	O
+residues	O
+;	O
+TM4	O
+-	O
+25	O
+residues	O
+.	O
+
+Two	O
+more	O
+residues	O
+could	O
+be	O
+added	O
+onto	O
+the	O
+N	O
+-	O
+terminal	O
+part	O
+of	O
+TM2	O
+;	O
+however	O
+,	O
+relatively	O
+small	O
+sequence	O
+conservation	O
+of	O
+these	O
+residues	O
+among	O
+tetraspanins	O
+and	O
+occurrence	O
+of	O
+polar	O
+/	O
+charged	O
+side	O
+chains	O
+in	O
+some	O
+tetraspanins	O
+precluded	O
+us	O
+from	O
+doing	O
+so	O
+for	O
+the	O
+global	O
+alignment	O
+.	O
+
+Figures	O
+1	O
+and	O
+2	O
+show	O
+a	O
+multiple	O
+sequence	O
+alignment	O
+of	O
+four	O
+TM	O
+domains	O
+of	O
+28	O
+human	B
+tetraspanins	O
+.	O
+
+For	O
+each	O
+position	O
+within	O
+the	O
+domains	O
+,	O
+consensus	O
+residues	O
+were	O
+determined	O
+and	O
+classified	O
+(	O
+with	O
+individual	O
+color	O
+code	O
+)	O
+in	O
+4	O
+categories	O
+:	O
+1	O
+)	O
+large	O
+hydrophobic	O
+residues	O
+(	O
+including	O
+Val	O
+,	O
+Met	O
+,	O
+Leu	O
+,	O
+Ile	O
+,	O
+Phe	O
+,	O
+Tyr	O
+,	O
+Trp	O
+)	O
+,	O
+2	O
+)	O
+small	O
+residues	O
+(	O
+Gly	O
+,	O
+Ala	O
+,	O
+Ser	O
+and	O
+Thr	O
+)	O
+,	O
+3	O
+)	O
+Cys	O
+,	O
+and	O
+4	O
+)	O
+Asn	O
+.	O
+
+When	O
+more	O
+than	O
+two	O
+types	O
+of	O
+residues	O
+occupied	O
+a	O
+given	O
+position	O
+in	O
+a	O
+TM	O
+,	O
+a	O
+dual	O
+-	O
+color	O
+pattern	O
+that	O
+reflected	O
+the	O
+prevalence	O
+of	O
+the	O
+particular	O
+residue	O
+type	O
+was	O
+used	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Cysteine	O
+residues	O
+were	O
+shown	O
+separately	O
+due	O
+to	O
+their	O
+importance	O
+as	O
+palmitoylation	O
+target	O
+sites	O
+.	O
+
+The	O
+highly	O
+conserved	O
+asparagine	O
+residue	O
+in	O
+TM1	O
+was	O
+considered	O
+separately	O
+.	O
+
+No	O
+proline	O
+residues	O
+are	O
+found	O
+in	O
+TM	O
+domains	O
+1	O
+-	O
+3	O
+of	O
+human	B
+tetraspanins	O
+.	O
+
+An	O
+inspection	O
+of	O
+the	O
+multiple	O
+sequence	O
+alignment	O
+reveals	O
+a	O
+repeating	O
+heptad	O
+amino	O
+acid	O
+pattern	O
+,	O
+(	O
+abcdefg	O
+)	O
+n	O
+,	O
+in	O
+TM1	O
+,	O
+2	O
+and	O
+3	O
+(	O
+Figure	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+Heptad	O
+repeats	O
+promote	O
+helical	O
+coiled	O
+coil	O
+interactions	O
+in	O
+multiple	O
+soluble	O
+and	O
+membrane	O
+-	O
+spanning	O
+proteins	O
+[	O
+29	O
+-	O
+31	O
+]	O
+.	O
+
+In	O
+the	O
+heptad	O
+repeat	O
+,	O
+hydrophobic	O
+residues	O
+in	O
+positions	O
+a	O
+and	O
+d	O
+are	O
+of	O
+special	O
+importance	O
+,	O
+as	O
+they	O
+directly	O
+mediate	O
+interhelical	O
+contacts	O
+by	O
+creating	O
+a	O
+tight	O
+knobs	O
+-	O
+into	O
+-	O
+holes	O
+packing	O
+in	O
+the	O
+coiled	O
+coil	O
+structure	O
+[	O
+32	O
+]	O
+.	O
+
+For	O
+instance	O
+,	O
+in	O
+the	O
+leucine	O
+zipper	O
+of	O
+the	O
+yeast	B
+transcription	O
+factor	O
+GCN4	O
+,	O
+positions	O
+a	O
+and	O
+d	O
+contain	O
+Val	O
+and	O
+Leu	O
+residues	O
+,	O
+respectively	O
+,	O
+with	O
+an	O
+Asn	O
+residue	O
+in	O
+a	O
+single	O
+a	O
+position	O
+forming	O
+a	O
+hydrogen	O
+bond	O
+across	O
+the	O
+GCN4	O
+dimer	O
+interface	O
+[	O
+33	O
+]	O
+.	O
+
+In	O
+TM1	O
+of	O
+tetraspanins	O
+,	O
+highly	O
+conserved	O
+Asn	O
+,	O
+Gly	O
+and	O
+Gly	O
+residues	O
+(	O
+numbers	O
+18	O
+,	O
+25	O
+and	O
+32	O
+in	O
+the	O
+CD9	O
+sequence	O
+)	O
+appear	O
+at	O
+d	O
+positions	O
+of	O
+the	O
+heptad	O
+repeats	O
+,	O
+and	O
+residues	O
+14	O
+,	O
+21	O
+and	O
+28	O
+are	O
+at	O
+a	O
+positions	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+In	O
+TM2	O
+,	O
+residues	O
+67	O
+,	O
+74	O
+and	O
+81	O
+(	O
+consensus	O
+Gly	O
+,	O
+Gly	O
+and	O
+Ala	O
+,	O
+respectively	O
+)	O
+occupy	O
+a	O
+positions	O
+,	O
+whereas	O
+residues	O
+63	O
+,	O
+70	O
+and	O
+77	O
+are	O
+at	O
+d	O
+positions	O
+.	O
+
+Another	O
+highly	O
+conserved	O
+glycine	O
+,	O
+Gly80	O
+,	O
+occupies	O
+the	O
+3rd	O
+g	O
+position	O
+in	O
+TM2	O
+.	O
+
+In	O
+TM3	O
+,	O
+the	O
+conserved	O
+pattern	O
+consists	O
+of	O
+two	O
+leucine	O
+residues	O
+(	O
+Leu89	O
+and	O
+Leu96	O
+)	O
+and	O
+a	O
+glutamate	O
+/	O
+glutamine	O
+residue	O
+(	O
+Glu	O
+/	O
+Gln103	O
+)	O
+in	O
+a	O
+positions	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+Two	O
+d	O
+positions	O
+are	O
+also	O
+conserved	O
+-	O
+Phe	O
+/	O
+Tyr92	O
+and	O
+Ile	O
+/	O
+Val	O
+/	O
+Leu99	O
+.	O
+
+TM4	O
+lacks	O
+a	O
+conserved	O
+heptad	O
+pattern	O
+and	O
+has	O
+only	O
+a	O
+single	O
+conserved	O
+position	O
+,	O
+Glu	O
+/	O
+Gln209	O
+(	O
+with	O
+four	O
+exceptions	O
+)	O
+.	O
+
+These	O
+features	O
+of	O
+TM1	O
+-	O
+4	O
+of	O
+tetraspanins	O
+are	O
+displayed	O
+on	O
+helical	O
+wheel	O
+diagrams	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+Analysis	O
+of	O
+TM1	O
+sequences	O
+
+The	O
+conserved	O
+Asn	O
+-	O
+Gly	O
+-	O
+Gly	O
+motif	O
+,	O
+occupying	O
+designated	O
+d	O
+positions	O
+of	O
+the	O
+heptad	O
+repeat	O
+,	O
+is	O
+the	O
+most	O
+prominent	O
+structural	O
+feature	O
+of	O
+TM1	O
+.	O
+
+We	O
+also	O
+compared	O
+sequences	O
+of	O
+CD9	O
+orthologs	O
+from	O
+10	O
+different	O
+organisms	O
+(	O
+the	O
+most	O
+available	O
+for	O
+any	O
+tetraspanin	O
+)	O
+to	O
+gain	O
+further	O
+insight	O
+into	O
+conservation	O
+and	O
+variability	O
+of	O
+the	O
+TM1	O
+sequence	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+4	O
+,	O
+positions	O
+a	O
+,	O
+d	O
+and	O
+g	O
+in	O
+TM1	O
+are	O
+among	O
+the	O
+most	O
+conserved	O
+(	O
+0	O
+,	O
+1	O
+and	O
+1	O
+substitution	O
+,	O
+respectively	O
+)	O
+,	O
+while	O
+interspecies	O
+variability	O
+tends	O
+to	O
+occur	O
+in	O
+other	O
+positions	O
+:	O
+b	O
+(	O
+5	O
+substitutions	O
+)	O
+,	O
+c	O
+(	O
+4	O
+substitutions	O
+)	O
+,	O
+e	O
+(	O
+4	O
+substitutions	O
+)	O
+and	O
+f	O
+(	O
+4	O
+substitutions	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+positions	O
+typically	O
+involved	O
+in	O
+coiled	O
+coil	O
+interactions	O
+(	O
+a	O
+and	O
+d	O
+)	O
+are	O
+the	O
+most	O
+conserved	O
+.	O
+
+When	O
+residues	O
+of	O
+TM1	O
+are	O
+plotted	O
+as	O
+a	O
+helical	O
+wheel	O
+,	O
+additional	O
+structural	O
+features	O
+are	O
+revealed	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+There	O
+are	O
+highly	O
+conserved	O
+aliphatic	O
+and	O
+aromatic	O
+residues	O
+in	O
+the	O
+first	O
+three	O
+a	O
+positions	O
+of	O
+the	O
+heptad	O
+motif	O
+(	O
+Phe15	O
+,	O
+Trp22	O
+and	O
+Leu29	O
+in	O
+CD9	O
+)	O
+,	O
+as	O
+well	O
+as	O
+in	O
+g	O
+positions	O
+(	O
+Leu14	O
+,	O
+Phe21	O
+,	O
+Val28	O
+in	O
+CD9	O
+)	O
+.	O
+
+The	O
+"	O
+ridges	O
+"	O
+formed	O
+by	O
+these	O
+bulky	O
+residues	O
+are	O
+flanking	O
+the	O
+"	O
+groove	O
+"	O
+-	O
+forming	O
+Gly	O
+residues	O
+of	O
+the	O
+Asn	O
+-	O
+Gly	O
+-	O
+Gly	O
+position	O
+d	O
+motif	O
+.	O
+
+In	O
+contrast	O
+,	O
+b	O
+,	O
+c	O
+,	O
+e	O
+and	O
+f	O
+positions	O
+show	O
+an	O
+overall	O
+higher	O
+variability	O
+among	O
+tetraspanins	O
+,	O
+as	O
+also	O
+seen	O
+in	O
+the	O
+comparison	O
+of	O
+CD9	O
+orthologs	O
+described	O
+above	O
+.	O
+
+Analysis	O
+of	O
+TM2	O
+sequences	O
+
+A	O
+landmark	O
+feature	O
+of	O
+TM2	O
+in	O
+tetraspanins	O
+is	O
+the	O
+presence	O
+of	O
+highly	O
+conserved	O
+glycine	O
+residues	O
+(	O
+Gly67	O
+,	O
+74	O
+,	O
+77	O
+and	O
+80	O
+in	O
+CD9	O
+,	O
+Figure	O
+1	O
+)	O
+.	O
+
+Other	O
+substitutions	O
+at	O
+these	O
+positions	O
+are	O
+almost	O
+exclusively	O
+small	O
+residues	O
+,	O
+such	O
+as	O
+Ala	O
+or	O
+Ser	O
+.	O
+
+In	O
+addition	O
+,	O
+Ala	O
+,	O
+Ser	O
+or	O
+Thr	O
+occupy	O
+position	O
+81	O
+.	O
+
+This	O
+residue	O
+,	O
+together	O
+with	O
+Gly67	O
+and	O
+Gly74	O
+,	O
+forms	O
+face	O
+a	O
+of	O
+the	O
+helix	O
+.	O
+
+Residue	O
+Gly77	O
+(	O
+position	O
+d	O
+)	O
+is	O
+preceded	O
+by	O
+conserved	O
+,	O
+chiefly	O
+large	O
+hydrophobic	O
+residues	O
+on	O
+the	O
+same	O
+helical	O
+face	O
+(	O
+Leu63	O
+and	O
+Met70	O
+in	O
+CD9	O
+)	O
+.	O
+
+Extremely	O
+conserved	O
+Gly80	O
+falls	O
+into	O
+heptad	O
+position	O
+g	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+Among	O
+CD9	O
+orthologs	O
+,	O
+heptad	O
+positions	O
+a	O
+and	O
+d	O
+are	O
+absolutely	O
+conserved	O
+,	O
+whereas	O
+other	O
+positions	O
+have	O
+the	O
+following	O
+number	O
+of	O
+substitutions	O
+:	O
+b	O
+-	O
+3	O
+;	O
+c	O
+-	O
+2	O
+;	O
+e	O
+-	O
+1	O
+;	O
+f	O
+-	O
+3	O
+;	O
+g	O
+-	O
+1	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+Two	O
+of	O
+the	O
+f	O
+position	O
+residues	O
+in	O
+TM2	O
+(	O
+65	O
+and	O
+79	O
+)	O
+also	O
+show	O
+higher	O
+variability	O
+among	O
+different	O
+tetraspanins	O
+(	O
+Figures	O
+1	O
+,	O
+3	O
+)	O
+.	O
+
+Cysteine	O
+residues	O
+are	O
+frequently	O
+found	O
+near	O
+the	O
+cytoplasmic	O
+end	O
+of	O
+TM2	O
+helix	O
+at	O
+positions	O
+78	O
+and	O
+79	O
+;	O
+these	O
+cysteines	O
+are	O
+likely	O
+to	O
+be	O
+palmitoylated	O
+.	O
+
+Analysis	O
+of	O
+TM3	O
+and	O
+TM4	O
+sequences	O
+
+The	O
+TM3	O
+domain	O
+provides	O
+another	O
+example	O
+of	O
+the	O
+heptad	O
+repeat	O
+pattern	O
+.	O
+
+Position	O
+a	O
+is	O
+occupied	O
+by	O
+two	O
+highly	O
+conserved	O
+leucine	O
+and	O
+a	O
+glutamate	O
+/	O
+glutamine	O
+residue	O
+(	O
+Leu89	O
+,	O
+Leu96	O
+and	O
+Glu	O
+/	O
+Gln103	O
+in	O
+CD9	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+two	O
+d	O
+positions	O
+are	O
+conserved	O
+-	O
+Phe	O
+/	O
+Tyr92	O
+(	O
+aromatic	O
+residue	O
+)	O
+and	O
+Ile	O
+/	O
+Val99	O
+(	O
+beta	O
+-	O
+branched	O
+aliphatic	O
+residue	O
+;	O
+Figures	O
+2	O
+,	O
+3	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+residue	O
+100	O
+in	O
+position	O
+e	O
+is	O
+generally	O
+Phe	O
+or	O
+Leu	O
+.	O
+
+Among	O
+CD9	O
+orthologs	O
+,	O
+position	O
+a	O
+has	O
+1	O
+substitution	O
+,	O
+positions	O
+b	O
+,	O
+c	O
+and	O
+f	O
+each	O
+have	O
+6	O
+,	O
+positions	O
+d	O
+and	O
+e	O
+each	O
+have	O
+2	O
+,	O
+and	O
+g	O
+has	O
+4	O
+.	O
+
+Thus	O
+,	O
+as	O
+for	O
+TM1	O
+and	O
+TM2	O
+,	O
+positions	O
+a	O
+and	O
+d	O
+are	O
+among	O
+the	O
+most	O
+conserved	O
+,	O
+but	O
+overall	O
+TM3	O
+has	O
+more	O
+variable	O
+positions	O
+than	O
+TM1	O
+or	O
+TM2	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+Less	O
+than	O
+half	O
+of	O
+TM3	O
+sequences	O
+contain	O
+cysteine	O
+residues	O
+,	O
+and	O
+those	O
+tend	O
+to	O
+occur	O
+at	O
+the	O
+internal	O
+positions	O
+of	O
+the	O
+helix	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+TM4	O
+shows	O
+less	O
+conservation	O
+among	O
+various	O
+tetraspanin	O
+family	O
+members	O
+than	O
+the	O
+other	O
+TM	O
+domains	O
+(	O
+Figures	O
+2	O
+,	O
+3	O
+)	O
+.	O
+
+The	O
+only	O
+highly	O
+conserved	O
+feature	O
+is	O
+the	O
+glutamate	O
+/	O
+glutamine	O
+residue	O
+in	O
+position	O
+209	O
+.	O
+
+In	O
+addition	O
+,	O
+one	O
+or	O
+two	O
+cysteine	O
+residues	O
+can	O
+be	O
+found	O
+at	O
+the	O
+C	O
+-	O
+terminal	O
+end	O
+of	O
+TM4	O
+in	O
+some	O
+tetraspanins	O
+(	O
+e	O
+.	O
+g	O
+.	O
+CD9	O
+,	O
+CD81	O
+,	O
+CD151	O
+)	O
+,	O
+and	O
+many	O
+sequences	O
+contain	O
+additional	O
+polar	O
+residues	O
+(	O
+Arg	O
+,	O
+Lys	O
+,	O
+His	O
+,	O
+Asn	O
+,	O
+Gln	O
+)	O
+.	O
+
+No	O
+conserved	O
+heptad	O
+motif	O
+was	O
+identified	O
+in	O
+TM4	O
+,	O
+as	O
+also	O
+confirmed	O
+by	O
+analysis	O
+of	O
+substitutions	O
+in	O
+CD9	O
+orthologs	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Mutational	O
+analysis	O
+of	O
+conserved	O
+glycine	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+
+The	O
+conserved	O
+nature	O
+of	O
+the	O
+Asn	O
+and	O
+Gly	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+prompted	O
+an	O
+analysis	O
+of	O
+their	O
+functional	O
+role	O
+.	O
+
+To	O
+this	O
+end	O
+,	O
+we	O
+have	O
+probed	O
+whether	O
+mutations	O
+of	O
+these	O
+residues	O
+destabilize	O
+the	O
+protein	O
+molecule	O
+.	O
+
+We	O
+expressed	O
+a	O
+construct	O
+of	O
+the	O
+first	O
+and	O
+second	O
+TMs	O
+of	O
+CD9	O
+,	O
+connected	O
+by	O
+the	O
+small	O
+extracellular	O
+loop	O
+,	O
+and	O
+tagged	O
+with	O
+a	O
+C	O
+-	O
+terminal	O
+green	O
+fluorescent	O
+protein	O
+(	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+molecule	O
+)	O
+.	O
+
+In	O
+human	B
+rhabdomyosarcoma	O
+RD	O
+cells	O
+,	O
+the	O
+wild	O
+-	O
+type	O
+fusion	O
+protein	O
+localized	O
+mostly	O
+in	O
+a	O
+reticular	O
+,	O
+intracellular	O
+pattern	O
+,	O
+without	O
+forming	O
+any	O
+large	O
+aggregates	O
+(	O
+Figure	O
+5	O
+,	O
+panel	O
+A	O
+)	O
+.	O
+
+Remarkably	O
+,	O
+when	O
+double	O
+mutants	O
+Gly25Leu	O
++	O
+Gly32Leu	O
+and	O
+Gly67Leu	O
++	O
+Gly74Leu	O
+were	O
+expressed	O
+,	O
+the	O
+protein	O
+formed	O
+distinct	O
+large	O
+aggregates	O
+in	O
+a	O
+high	O
+proportion	O
+of	O
+cells	O
+(	O
+Figure	O
+5	O
+,	O
+panels	O
+C	O
+and	O
+E	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+double	O
+mutant	O
+Gly77Leu	O
++	O
+Gly80Leu	O
+did	O
+not	O
+form	O
+such	O
+aggregates	O
+(	O
+Figure	O
+5	O
+,	O
+panel	O
+G	O
+)	O
+.	O
+
+Results	O
+with	O
+respective	O
+single	O
+mutants	O
+were	O
+similar	O
+to	O
+that	O
+with	O
+double	O
+mutants	O
+,	O
+with	O
+the	O
+aggregation	O
+being	O
+somewhat	O
+more	O
+pronounced	O
+for	O
+Leu	O
+substitutions	O
+of	O
+Gly67	O
+and	O
+Gly74	O
+compared	O
+to	O
+Gly25	O
+and	O
+Gly32	O
+mutations	O
+.	O
+
+No	O
+aggregation	O
+was	O
+observed	O
+for	O
+Asn18Ser	O
+and	O
+Asn18Tyr	O
+mutants	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Also	O
+,	O
+nearly	O
+identical	O
+results	O
+were	O
+obtained	O
+with	O
+human	B
+HT1080	O
+cells	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+We	O
+interpret	O
+these	O
+results	O
+as	O
+an	O
+indication	O
+that	O
+aggregating	O
+mutants	O
+are	O
+destabilized	O
+or	O
+misfolded	O
+while	O
+non	O
+-	O
+aggregating	O
+mutants	O
+retain	O
+the	O
+wild	O
+-	O
+type	O
+conformation	O
+.	O
+
+Intriguingly	O
+,	O
+mutations	O
+to	O
+the	O
+conserved	O
+GG7	O
+motifs	O
+caused	O
+protein	O
+aggregation	O
+while	O
+the	O
+mutation	O
+of	O
+other	O
+glycines	O
+had	O
+no	O
+detectable	O
+effect	O
+.	O
+
+These	O
+results	O
+also	O
+suggest	O
+that	O
+wild	O
+-	O
+type	O
+GFP	O
+,	O
+which	O
+has	O
+weak	O
+tendency	O
+to	O
+self	O
+-	O
+associate	O
+,	O
+could	O
+enhance	O
+non	O
+-	O
+specific	O
+interactions	O
+of	O
+destabilized	O
+mutant	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+CD9	O
+moieties	O
+,	O
+leading	O
+to	O
+their	O
+aggregation	O
+.	O
+
+Consistent	O
+with	O
+this	O
+hypothesis	O
+,	O
+the	O
+aggregation	O
+of	O
+Gly25Leu	O
++	O
+Gly32Leu	O
+and	O
+Gly67Leu	O
++	O
+Gly74Leu	O
+double	O
+mutants	O
+was	O
+suppressed	O
+when	O
+monomeric	O
+GFP	O
+molecule	O
+,	O
+Leu221Lys	O
+[	O
+34	O
+]	O
+was	O
+used	O
+(	O
+Figure	O
+5	O
+,	O
+panels	O
+D	O
+and	O
+F	O
+)	O
+.	O
+
+The	O
+use	O
+of	O
+monomeric	O
+GFP	O
+did	O
+not	O
+affect	O
+intercellular	O
+localization	O
+of	O
+wild	O
+-	O
+type	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+(	O
+Figure	O
+5	O
+,	O
+panel	O
+B	O
+)	O
+,	O
+or	O
+a	O
+Gly77Leu	O
++	O
+Gly80Leu	O
+double	O
+mutant	O
+(	O
+Figure	O
+5	O
+,	O
+panel	O
+H	O
+)	O
+.	O
+
+In	O
+summary	O
+,	O
+Leu	O
+substitutions	O
+of	O
+Gly	O
+residues	O
+that	O
+are	O
+part	O
+of	O
+the	O
+Asn	O
+-	O
+Gly	O
+-	O
+Gly	O
+(	O
+NGG7	O
+)	O
+motif	O
+in	O
+TM1	O
+,	O
+or	O
+Gly	O
+-	O
+Gly	O
+-	O
+Ala	O
+(	O
+GGA7	O
+)	O
+motif	O
+in	O
+TM2	O
+,	O
+resulted	O
+in	O
+destabilization	O
+and	O
+aggregation	O
+of	O
+GFP	O
+-	O
+fused	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+proteins	O
+,	O
+whereas	O
+substitutions	O
+of	O
+Gly77	O
+or	O
+Gly80	O
+,	O
+which	O
+are	O
+not	O
+part	O
+of	O
+these	O
+motifs	O
+(	O
+Figure	O
+3	O
+)	O
+,	O
+failed	O
+to	O
+show	O
+such	O
+aggregation	O
+.	O
+
+Prediction	O
+and	O
+modelling	O
+of	O
+interaction	O
+between	O
+TM1	O
+and	O
+TM2	O
+
+Consecutive	O
+helices	O
+in	O
+polytopic	O
+membrane	O
+proteins	O
+frequently	O
+interact	O
+[	O
+35	O
+]	O
+.	O
+
+Sequence	O
+analysis	O
+of	O
+TM1	O
+and	O
+TM2	O
+helices	O
+of	O
+tetraspanins	O
+reveals	O
+a	O
+remarkable	O
+complementarity	O
+in	O
+the	O
+distribution	O
+of	O
+large	O
+and	O
+small	O
+residues	O
+at	O
+heptad	O
+positions	O
+a	O
+and	O
+d	O
+along	O
+the	O
+helical	O
+axis	O
+(	O
+Figure	O
+3	O
+)	O
+,	O
+suggesting	O
+that	O
+these	O
+residues	O
+may	O
+interact	O
+.	O
+
+To	O
+further	O
+elucidate	O
+the	O
+potential	O
+for	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+,	O
+the	O
+putative	O
+interface	O
+was	O
+modeled	O
+using	O
+a	O
+novel	O
+algorithm	O
+that	O
+considers	O
+mutational	O
+data	O
+during	O
+each	O
+step	O
+of	O
+a	O
+Monte	O
+Carlo	O
+simulated	O
+annealing	O
+cycle	O
+(	O
+see	O
+Methods	O
+for	O
+details	O
+)	O
+.	O
+
+Specifically	O
+,	O
+Gly25Leu	O
+,	O
+Gly32Leu	O
+,	O
+Gly67Leu	O
+and	O
+Gly74Leu	O
+were	O
+scored	O
+as	O
+disruptive	O
+mutations	O
+,	O
+while	O
+Asn18Ser	O
+,	O
+Gly77Leu	O
+and	O
+Gly80Leu	O
+were	O
+scored	O
+as	O
+silent	O
+mutations	O
+,	O
+based	O
+on	O
+their	O
+effects	O
+on	O
+protein	O
+stability	O
+(	O
+Figure	O
+5	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+resulting	O
+model	O
+predicts	O
+left	O
+-	O
+handed	O
+crossing	O
+of	O
+TM1	O
+and	O
+TM2	O
+helices	O
+at	O
+an	O
+angle	O
+of	O
++	O
+28	O
+degrees	O
+.	O
+
+The	O
+key	O
+element	O
+of	O
+the	O
+structure	O
+is	O
+the	O
+apposition	O
+of	O
+bulky	O
+and	O
+small	O
+heptad	O
+position	O
+a	O
+and	O
+d	O
+residues	O
+,	O
+as	O
+follows	O
+:	O
+Gly32	O
+-	O
+Leu63	O
+;	O
+Gly67	O
+-	O
+Leu29	O
+;	O
+Gly25	O
+-	O
+Met70	O
+;	O
+Gly74	O
+-	O
+Trp22	O
+;	O
+Asn18	O
+-	O
+Gly77	O
+;	O
+Ala81	O
+-	O
+Phe15	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+Our	O
+model	O
+predicts	O
+that	O
+each	O
+of	O
+these	O
+residue	O
+pairs	O
+are	O
+in	O
+van	O
+der	O
+Waals	O
+contact	O
+.	O
+
+Additionally	O
+,	O
+two	O
+potential	O
+H	O
+-	O
+bonds	O
+are	O
+predicted	O
+in	O
+this	O
+model	O
+,	O
+indicating	O
+close	O
+packing	O
+:	O
+Gly67	O
+C	O
+alpha	O
+to	O
+Gly25	O
+carbonyl	O
+oxygen	O
+,	O
+and	O
+Trp22	O
+C	O
+alpha	O
+to	O
+Met70	O
+carbonyl	O
+oxygen	O
+.	O
+
+The	O
+packing	O
+is	O
+tighter	O
+in	O
+the	O
+ectodomain	O
+-	O
+proximal	O
+portion	O
+of	O
+the	O
+helices	O
+(	O
+Figure	O
+6	O
+,	O
+panel	O
+B	O
+)	O
+,	O
+as	O
+determined	O
+by	O
+C	O
+alpha	O
+-	O
+C	O
+alpha	O
+distances	O
+between	O
+interacting	O
+residue	O
+pairs	O
+.	O
+
+The	O
+key	O
+elements	O
+of	O
+the	O
+model	O
+are	O
+corroborated	O
+by	O
+the	O
+presence	O
+of	O
+apparently	O
+complementary	O
+substitutions	O
+in	O
+TM1	O
+and	O
+TM2	O
+sequences	O
+of	O
+different	O
+tetraspanins	O
+(	O
+Figure	O
+1	O
+,	O
+boxed	O
+residues	O
+)	O
+.	O
+
+For	O
+example	O
+,	O
+Gly74	O
+is	O
+predicted	O
+to	O
+interact	O
+with	O
+Trp22	O
+.	O
+
+In	O
+8	O
+of	O
+the	O
+10	O
+tetraspanins	O
+that	O
+contain	O
+a	O
+substitution	O
+for	O
+Gly74	O
+,	O
+a	O
+compensatory	O
+substitution	O
+occurs	O
+at	O
+the	O
+Trp22	O
+position	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Thus	O
+,	O
+a	O
+larger	O
+non	O
+-	O
+glycine	O
+side	O
+chain	O
+at	O
+position	O
+74	O
+may	O
+necessitate	O
+a	O
+less	O
+bulky	O
+non	O
+-	O
+Trp	O
+side	O
+chain	O
+in	O
+position	O
+22	O
+.	O
+
+Likewise	O
+,	O
+the	O
+presence	O
+of	O
+a	O
+C	O
+beta	O
+at	O
+position	O
+25	O
+,	O
+typically	O
+occupied	O
+by	O
+glycine	O
+,	O
+necessitates	O
+a	O
+non	O
+-	O
+beta	O
+-	O
+branched	O
+amino	O
+acid	O
+at	O
+position	O
+70	O
+,	O
+which	O
+is	O
+occupied	O
+by	O
+a	O
+beta	O
+-	O
+branched	O
+residue	O
+in	O
+nearly	O
+half	O
+of	O
+all	O
+cases	O
+.	O
+
+Indeed	O
+,	O
+we	O
+find	O
+that	O
+in	O
+each	O
+of	O
+5	O
+cases	O
+in	O
+which	O
+position	O
+25	O
+contains	O
+a	O
+C	O
+beta	O
+,	O
+a	O
+leucine	O
+residue	O
+occurs	O
+in	O
+position	O
+70	O
+.	O
+
+This	O
+analysis	O
+is	O
+consistent	O
+with	O
+our	O
+molecular	O
+model	O
+that	O
+suggests	O
+Leu70	O
+will	O
+pack	O
+most	O
+favorably	O
+against	O
+a	O
+C	O
+beta	O
+at	O
+position	O
+25	O
+than	O
+a	O
+beta	O
+-	O
+branched	O
+residue	O
+or	O
+a	O
+methionine	O
+.	O
+
+Role	O
+of	O
+TM1	O
+and	O
+TM2	O
+heptad	O
+motif	O
+residues	O
+in	O
+CD9	O
+dimerization	O
+
+To	O
+probe	O
+CD9	O
+dimerization	O
+,	O
+we	O
+used	O
+a	O
+cysteine	O
+-	O
+mediated	O
+cross	O
+-	O
+linking	O
+approach	O
+.	O
+
+We	O
+established	O
+previously	O
+a	O
+simple	O
+and	O
+efficient	O
+method	O
+for	O
+cysteine	O
+-	O
+mediated	O
+cross	O
+-	O
+linking	O
+[	O
+25	O
+]	O
+.	O
+
+After	O
+cells	O
+are	O
+pre	O
+-	O
+treated	O
+with	O
+2	O
+-	O
+BP	O
+for	O
+16	O
+-	O
+24	O
+hours	O
+to	O
+expose	O
+normally	O
+palmitoylated	O
+cysteines	O
+,	O
+the	O
+cysteines	O
+can	O
+be	O
+cross	O
+-	O
+linked	O
+using	O
+any	O
+of	O
+the	O
+following	O
+methods	O
+:	O
+a	O
+)	O
+Spontaneous	O
+oxidation	O
+in	O
+Brij97	O
+lysates	O
+(	O
+a	O
+condition	O
+that	O
+preserves	O
+tetraspanin	O
+-	O
+tetraspanin	O
+associations	O
+)	O
+,	O
+b	O
+)	O
+In	O
+situ	O
+cross	O
+-	O
+linking	O
+,	O
+by	O
+pre	O
+-	O
+lysis	O
+oxidation	O
+of	O
+cells	O
+with	O
+Cu2	O
++	O
+-	O
+phenanthroline	O
+(	O
+CuP	O
+)	O
+to	O
+promote	O
+disulfide	O
+bond	O
+formation	O
+.	O
+
+c	O
+)	O
+In	O
+situ	O
+cross	O
+-	O
+linking	O
+with	O
+thiol	O
+-	O
+reactive	O
+cross	O
+-	O
+linking	O
+agents	O
+of	O
+defined	O
+length	O
+(	O
+e	O
+.	O
+g	O
+.	O
+DTME	O
+,	O
+BMB	O
+)	O
+.	O
+
+The	O
+first	O
+two	O
+approaches	O
+produce	O
+in	O
+essence	O
+"	O
+zero	O
+-	O
+length	O
+"	O
+disulfides	O
+,	O
+indicative	O
+of	O
+close	O
+proximity	O
+of	O
+target	O
+cysteines	O
+and	O
+presumably	O
+high	O
+specificity	O
+of	O
+interaction	O
+.	O
+
+In	O
+contrast	O
+,	O
+chemical	O
+cross	O
+-	O
+linkers	O
+with	O
+6	O
+-	O
+20	O
+A	O
+spacer	O
+arm	O
+may	O
+cross	O
+-	O
+link	O
+with	O
+higher	O
+efficiency	O
+,	O
+but	O
+not	O
+necessarily	O
+higher	O
+specificity	O
+.	O
+
+However	O
+,	O
+they	O
+provide	O
+advantages	O
+such	O
+as	O
+variable	O
+membrane	O
+permeability	O
+,	O
+and	O
+potential	O
+linkage	O
+cleavability	O
+.	O
+
+For	O
+tetraspanins	O
+such	O
+as	O
+CD9	O
+,	O
+membrane	O
+-	O
+permeable	O
+cross	O
+-	O
+linker	O
+DTME	O
+(	O
+13	O
+.	O
+3	O
+A	O
+-	O
+long	O
+,	O
+reducible	O
+)	O
+provides	O
+highly	O
+specific	O
+and	O
+efficient	O
+cross	O
+-	O
+linking	O
+[	O
+25	O
+]	O
+.	O
+
+Here	O
+we	O
+have	O
+used	O
+a	O
+cysteine	O
+cross	O
+-	O
+linking	O
+strategy	O
+,	O
+in	O
+combination	O
+with	O
+cysteine	O
+-	O
+scanning	O
+mutagenesis	O
+,	O
+to	O
+map	O
+the	O
+residues	O
+from	O
+TM1	O
+and	O
+TM2	O
+contributing	O
+to	O
+the	O
+CD9	O
+dimerization	O
+interface	O
+.	O
+
+For	O
+subsequent	O
+cross	O
+-	O
+linking	O
+experiments	O
+using	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+protein	O
+,	O
+the	O
+non	O
+-	O
+dimerizing	O
+form	O
+of	O
+GFP	O
+was	O
+used	O
+.	O
+
+This	O
+avoids	O
+potential	O
+GFP	O
+-	O
+dependent	O
+dimerization	O
+and	O
+aggregation	O
+that	O
+can	O
+be	O
+observed	O
+with	O
+wild	O
+-	O
+type	O
+GFP	O
+,	O
+especially	O
+when	O
+fusions	O
+with	O
+transmembrane	O
+proteins	O
+are	O
+studied	O
+[	O
+36	O
+]	O
+.	O
+
+Importantly	O
+,	O
+the	O
+Leu221Lys	O
+mutation	O
+in	O
+GFP	O
+prevented	O
+aggregation	O
+of	O
+mutant	O
+forms	O
+of	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+,	O
+which	O
+was	O
+observed	O
+with	O
+wild	O
+-	O
+type	O
+GFP	O
+fusion	O
+(	O
+Figure	O
+5	O
+)	O
+.	O
+
+The	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+fragment	O
+of	O
+CD9	O
+contains	O
+three	O
+native	O
+cysteines	O
+-	O
+Cys9	O
+,	O
+Cys78	O
+and	O
+Cys79	O
+.	O
+
+Single	O
+-	O
+cysteine	O
+mutants	O
+of	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+were	O
+constructed	O
+,	O
+in	O
+which	O
+a	O
+cysteine	O
+was	O
+placed	O
+at	O
+various	O
+faces	O
+of	O
+TM1	O
+or	O
+TM2	O
+while	O
+all	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+cysteines	O
+were	O
+simultaneously	O
+replaced	O
+by	O
+serines	O
+.	O
+
+The	O
+mutant	O
+proteins	O
+were	O
+transiently	O
+expressed	O
+in	O
+RD	O
+cells	O
+(	O
+having	O
+little	O
+endogenous	O
+CD9	O
+)	O
+,	O
+which	O
+were	O
+then	O
+treated	O
+for	O
+16	O
+-	O
+18	O
+hours	O
+with	O
+2	O
+-	O
+BP	O
+.	O
+
+To	O
+achieve	O
+maximal	O
+specificity	O
+in	O
+cross	O
+-	O
+linking	O
+we	O
+used	O
+a	O
+"	O
+zero	O
+-	O
+length	O
+"	O
+agent	O
+,	O
+CuP	O
+.	O
+
+First	O
+,	O
+single	O
+-	O
+cysteine	O
+replacements	O
+were	O
+constructed	O
+for	O
+residues	O
+Leu14	O
+,	O
+Phe15	O
+,	O
+Gly16	O
+,	O
+Phe17	O
+and	O
+Asn18	O
+,	O
+covering	O
+just	O
+over	O
+one	O
+complete	O
+helical	O
+turn	O
+at	O
+the	O
+beginning	O
+of	O
+TM1	O
+.	O
+
+While	O
+residue	O
+Asn18	O
+is	O
+highly	O
+conserved	O
+,	O
+positions	O
+14	O
+,	O
+15	O
+and	O
+17	O
+are	O
+occupied	O
+by	O
+bulky	O
+hydrophobic	O
+residues	O
+in	O
+most	O
+tetraspanins	O
+,	O
+whereas	O
+position	O
+16	O
+shows	O
+less	O
+conservation	O
+(	O
+Figures	O
+1	O
+,	O
+4	O
+)	O
+.	O
+
+All	O
+of	O
+the	O
+single	O
+-	O
+cysteine	O
+mutants	O
+showed	O
+diffused	O
+pattern	O
+of	O
+protein	O
+localization	O
+,	O
+without	O
+any	O
+signs	O
+of	O
+aggregation	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+7A	O
+,	O
+the	O
+highest	O
+level	O
+of	O
+intermolecular	O
+cross	O
+-	O
+linking	O
+was	O
+observed	O
+for	O
+Leu14Cys	O
+and	O
+Phe17Cys	O
+mutants	O
+,	O
+a	O
+lower	O
+level	O
+for	O
+Phe15Cys	O
+and	O
+Gly16Cys	O
+mutants	O
+,	O
+and	O
+very	O
+little	O
+cross	O
+-	O
+linking	O
+for	O
+Asn18Cys	O
+substitution	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+:	O
+a	O
+)	O
+the	O
+first	O
+two	O
+transmembrane	O
+domains	O
+of	O
+CD9	O
+alone	O
+can	O
+mediate	O
+its	O
+dimerization	O
+,	O
+and	O
+b	O
+)	O
+the	O
+g	O
+and	O
+c	O
+residues	O
+of	O
+TM1	O
+(	O
+e	O
+.	O
+g	O
+.	O
+Leu14	O
+and	O
+Phe17	O
+,	O
+Figure	O
+3	O
+)	O
+are	O
+likely	O
+to	O
+be	O
+part	O
+of	O
+the	O
+intermolecular	O
+interface	O
+.	O
+
+Similarly	O
+,	O
+single	O
+-	O
+cysteine	O
+substitutions	O
+were	O
+made	O
+for	O
+residues	O
+Gly77	O
+,	O
+Gly80	O
+and	O
+Ala81	O
+in	O
+TM2	O
+;	O
+in	O
+addition	O
+,	O
+proteins	O
+carrying	O
+a	O
+single	O
+wild	O
+-	O
+type	O
+cysteine	O
+,	O
+Cys9	O
+,	O
+Cys78	O
+or	O
+Cys79	O
+,	O
+were	O
+tested	O
+.	O
+
+No	O
+protein	O
+aggregation	O
+was	O
+observed	O
+for	O
+any	O
+of	O
+these	O
+single	O
+-	O
+cysteine	O
+mutants	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+7B	O
+,	O
+the	O
+relatively	O
+low	O
+level	O
+of	O
+intermolecular	O
+cross	O
+-	O
+linking	O
+of	O
+wild	O
+-	O
+type	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+protein	O
+was	O
+enhanced	O
+dramatically	O
+in	O
+single	O
+-	O
+cysteine	O
+TM2	O
+mutants	O
+Gly80Cys	O
+and	O
+Ala81Cys	O
+.	O
+
+The	O
+Gly77Cys	O
+mutant	O
+also	O
+had	O
+an	O
+elevated	O
+level	O
+of	O
+cross	O
+-	O
+linking	O
+.	O
+
+In	O
+contrast	O
+,	O
+any	O
+of	O
+the	O
+three	O
+native	O
+cysteines	O
+(	O
+9	O
+,	O
+78	O
+and	O
+79	O
+)	O
+produced	O
+level	O
+of	O
+cross	O
+-	O
+linking	O
+not	O
+much	O
+greater	O
+than	O
+the	O
+wild	O
+-	O
+type	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+protein	O
+.	O
+
+Similar	O
+results	O
+were	O
+obtained	O
+with	O
+cysteine	O
+-	O
+reactive	O
+cross	O
+-	O
+linker	O
+BMB	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Likewise	O
+,	O
+comparable	O
+results	O
+were	O
+obtained	O
+with	O
+single	O
+-	O
+cysteine	O
+mutants	O
+of	O
+untagged	O
+,	O
+full	O
+-	O
+length	O
+CD9	O
+,	O
+using	O
+CuP	O
+(	O
+Figure	O
+7C	O
+)	O
+as	O
+well	O
+as	O
+DTME	O
+cross	O
+-	O
+linker	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+These	O
+cross	O
+-	O
+linking	O
+results	O
+for	O
+TM1	O
+and	O
+TM2	O
+are	O
+consistent	O
+with	O
+our	O
+model	O
+that	O
+places	O
+residues	O
+Leu14	O
+,	O
+Phe17	O
+and	O
+Gly80	O
+on	O
+the	O
+same	O
+side	O
+of	O
+the	O
+TM1	O
+-	O
+TM2	O
+pair	O
+(	O
+Figure	O
+6	O
+,	O
+panel	O
+C	O
+)	O
+.	O
+
+The	O
+strong	O
+cross	O
+-	O
+linking	O
+with	O
+Leu14Cys	O
+,	O
+Phe17Cys	O
+and	O
+Gly80Cys	O
+places	O
+the	O
+intermolecular	O
+interface	O
+toward	O
+the	O
+c	O
+and	O
+g	O
+phases	O
+of	O
+the	O
+TM1	O
+helix	O
+,	O
+and	O
+the	O
+g	O
+phase	O
+of	O
+the	O
+TM2	O
+helix	O
+,	O
+away	O
+from	O
+its	O
+e	O
+and	O
+f	O
+faces	O
+containing	O
+wild	O
+-	O
+type	O
+cysteines	O
+78	O
+and	O
+79	O
+.	O
+
+Critical	O
+residues	O
+at	O
+the	O
+TM1	O
+-	O
+TM2	O
+interface	O
+also	O
+affect	O
+dimerization	O
+indirectly	O
+.	O
+
+To	O
+assess	O
+specific	O
+CD9	O
+dimerization	O
+,	O
+we	O
+used	O
+a	O
+Gly80Cys	O
+substitution	O
+at	O
+the	O
+intermolecular	O
+interface	O
+for	O
+cross	O
+-	O
+linking	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+8A	O
+,	O
+single	O
+replacements	O
+of	O
+conserved	O
+heptad	O
+residues	O
+in	O
+positions	O
+18	O
+,	O
+25	O
+,	O
+32	O
+,	O
+67	O
+and	O
+74	O
+(	O
+Asn18Ser	O
+,	O
+Gly25	O
+/	O
+32	O
+/	O
+67	O
+/	O
+74	O
+-	O
+-	O
+>	O
+Leu	O
+)	O
+strongly	O
+decreased	O
+the	O
+cross	O
+-	O
+linking	O
+mediated	O
+by	O
+Cys80	O
+.	O
+
+The	O
+effect	O
+was	O
+most	O
+pronounced	O
+for	O
+mutations	O
+of	O
+residues	O
+,	O
+Gly32	O
+and	O
+Gly67	O
+,	O
+located	O
+in	O
+the	O
+tightly	O
+packed	O
+extracellular	O
+end	O
+of	O
+TM	O
+helices	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+mutations	O
+of	O
+residues	O
+closer	O
+to	O
+the	O
+cytoplasmic	O
+end	O
+of	O
+TM2	O
+(	O
+Gly74	O
+and	O
+especially	O
+Ala81	O
+)	O
+had	O
+only	O
+modest	O
+to	O
+very	O
+little	O
+effect	O
+on	O
+cross	O
+-	O
+linking	O
+.	O
+
+Relatively	O
+low	O
+efficiency	O
+of	O
+intermolecular	O
+cross	O
+-	O
+linking	O
+via	O
+native	O
+residues	O
+Cys9	O
+,	O
+78	O
+,	O
+and	O
+79	O
+(	O
+Figures	O
+7B	O
+,	O
+C	O
+)	O
+correlates	O
+well	O
+with	O
+the	O
+predicted	O
+location	O
+of	O
+Cys78	O
+and	O
+79	O
+away	O
+from	O
+the	O
+dimeric	O
+interface	O
+(	O
+Figure	O
+3	O
+)	O
+,	O
+and	O
+suggests	O
+that	O
+the	O
+extramembrane	O
+N	O
+-	O
+terminal	O
+part	O
+of	O
+CD9	O
+(	O
+residues	O
+1	O
+-	O
+13	O
+)	O
+does	O
+not	O
+self	O
+-	O
+associate	O
+.	O
+
+We	O
+next	O
+examined	O
+whether	O
+mutations	O
+of	O
+conserved	O
+Asn	O
+and	O
+Gly	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+decreased	O
+low	O
+-	O
+level	O
+background	O
+cross	O
+-	O
+linking	O
+via	O
+native	O
+cysteines	O
+.	O
+
+As	O
+expected	O
+,	O
+these	O
+mutations	O
+had	O
+virtually	O
+no	O
+effect	O
+on	O
+dimer	O
+formation	O
+of	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+(	O
+Figure	O
+8B	O
+)	O
+.	O
+
+The	O
+level	O
+of	O
+covalent	O
+dimer	O
+formed	O
+was	O
+not	O
+diminished	O
+for	O
+triple	O
+Asn18Ser	O
++	O
+Gly25Leu	O
++	O
+Gly32Leu	O
+and	O
+double	O
+Gly67Leu	O
++	O
+Gly74Leu	O
+mutants	O
+,	O
+compared	O
+to	O
+wild	O
+-	O
+type	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+CD9	O
+molecule	O
+.	O
+
+Similarly	O
+,	O
+the	O
+same	O
+triple	O
+and	O
+double	O
+mutations	O
+in	O
+the	O
+context	O
+of	O
+full	O
+-	O
+length	O
+CD9	O
+-	O
+GFP	O
+protein	O
+(	O
+with	O
+six	O
+cysteines	O
+)	O
+produced	O
+wild	O
+-	O
+type	O
+levels	O
+of	O
+cross	O
+-	O
+linking	O
+(	O
+Figure	O
+8C	O
+)	O
+.	O
+
+We	O
+interpret	O
+these	O
+findings	O
+as	O
+evidence	O
+for	O
+at	O
+least	O
+two	O
+types	O
+of	O
+associations	O
+between	O
+CD9	O
+molecules	O
+:	O
+primary	O
+,	O
+involving	O
+residues	O
+14	O
+,	O
+17	O
+and	O
+80	O
+,	O
+and	O
+dependent	O
+on	O
+integrity	O
+of	O
+conserved	O
+heptad	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+,	O
+and	O
+less	O
+efficient	O
+secondary	O
+interactions	O
+,	O
+probably	O
+representing	O
+random	O
+collision	O
+events	O
+,	O
+and	O
+independent	O
+of	O
+the	O
+heptad	O
+residues	O
+(	O
+see	O
+Discussion	O
+for	O
+more	O
+details	O
+)	O
+.	O
+
+TM3	O
+and	O
+TM4	O
+cysteine	O
+residues	O
+in	O
+CD9	O
+dimerization	O
+
+After	O
+identifying	O
+the	O
+roles	O
+of	O
+conserved	O
+TM1	O
+and	O
+TM2	O
+residues	O
+in	O
+CD9	O
+dimerization	O
+,	O
+we	O
+next	O
+probed	O
+whether	O
+residues	O
+proximal	O
+to	O
+TM	O
+domains	O
+3	O
+and	O
+4	O
+are	O
+also	O
+involved	O
+.	O
+
+To	O
+this	O
+end	O
+,	O
+disulfide	O
+cross	O
+-	O
+linking	O
+of	O
+full	O
+-	O
+length	O
+CD9	O
+molecules	O
+containing	O
+3	O
+C	O
+-	O
+terminal	O
+cysteines	O
+(	O
+87	O
+,	O
+just	O
+before	O
+TM3	O
+;	O
+218	O
+and	O
+219	O
+in	O
+TM4	O
+)	O
+or	O
+3	O
+N	O
+-	O
+terminal	O
+cysteines	O
+(	O
+9	O
+,	O
+78	O
+and	O
+79	O
+)	O
+was	O
+compared	O
+(	O
+Figure	O
+9	O
+)	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+C	O
+-	O
+terminal	O
+cysteines	O
+were	O
+only	O
+slightly	O
+better	O
+than	O
+N	O
+-	O
+terminal	O
+cysteines	O
+with	O
+respect	O
+to	O
+detection	O
+of	O
+CD9	O
+dimers	O
+.	O
+
+However	O
+,	O
+markedly	O
+more	O
+trimers	O
+and	O
+tetramers	O
+were	O
+detected	O
+using	O
+C	O
+-	O
+terminal	O
+cysteines	O
+.	O
+
+Thus	O
+,	O
+residues	O
+87	O
+,	O
+218	O
+and	O
+219	O
+at	O
+TM3	O
+and	O
+TM4	O
+in	O
+CD9	O
+can	O
+together	O
+form	O
+contacts	O
+across	O
+the	O
+dimeric	O
+interface	O
+and	O
+also	O
+additional	O
+contacts	O
+with	O
+other	O
+neighboring	O
+CD9	O
+molecules	O
+.	O
+
+Discussion	O
+
+Here	O
+we	O
+provide	O
+the	O
+first	O
+detailed	O
+analysis	O
+of	O
+tetraspanin	O
+protein	O
+transmembrane	O
+domains	O
+.	O
+
+First	O
+,	O
+we	O
+show	O
+1	O
+)	O
+the	O
+presence	O
+of	O
+a	O
+heptad	O
+repeat	O
+motif	O
+in	O
+TM1	O
+and	O
+TM2	O
+,	O
+containing	O
+highly	O
+conserved	O
+Asn	O
+and	O
+Gly	O
+residues	O
+,	O
+2	O
+)	O
+a	O
+leucine	O
+and	O
+glutamate	O
+/	O
+glutamine	O
+-	O
+containing	O
+heptad	O
+motif	O
+in	O
+TM3	O
+,	O
+and	O
+3	O
+)	O
+high	O
+variability	O
+and	O
+absence	O
+of	O
+heptad	O
+repeats	O
+in	O
+TM4	O
+sequences	O
+.	O
+
+Second	O
+,	O
+we	O
+provide	O
+evidence	O
+for	O
+a	O
+specific	O
+,	O
+intramolecular	O
+interaction	O
+between	O
+TM1	O
+and	O
+TM2	O
+domains	O
+,	O
+in	O
+which	O
+bulky	O
+hydrophobic	O
+residues	O
+pack	O
+against	O
+GG7	O
+motif	O
+,	O
+and	O
+present	O
+a	O
+molecular	O
+model	O
+for	O
+this	O
+interaction	O
+.	O
+
+Third	O
+,	O
+experimental	O
+mapping	O
+of	O
+the	O
+CD9	O
+dimerization	O
+interface	O
+firmly	O
+establishes	O
+an	O
+additional	O
+role	O
+for	O
+conserved	O
+TM1	O
+and	O
+TM2	O
+residues	O
+in	O
+dimeric	O
+intermolecular	O
+interactions	O
+.	O
+
+Fourth	O
+,	O
+preliminary	O
+evidence	O
+is	O
+provided	O
+to	O
+suggest	O
+that	O
+TM3	O
+and	O
+TM4	O
+domains	O
+contribute	O
+to	O
+expansion	O
+of	O
+CD9	O
+dimers	O
+into	O
+higher	O
+order	O
+multimers	O
+.	O
+
+Conserved	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+of	O
+tetraspanins	O
+:	O
+role	O
+in	O
+intramolecular	O
+packing	O
+
+We	O
+hypothesized	O
+that	O
+the	O
+first	O
+two	O
+transmembrane	O
+domains	O
+of	O
+tetraspanins	O
+might	O
+interact	O
+with	O
+each	O
+other	O
+because	O
+:	O
+a	O
+)	O
+consecutive	O
+TM	O
+domains	O
+frequently	O
+associate	O
+in	O
+known	O
+protein	O
+3D	O
+structures	O
+[	O
+35	O
+]	O
+,	O
+and	O
+b	O
+)	O
+they	O
+both	O
+contain	O
+a	O
+series	O
+of	O
+highly	O
+conserved	O
+amino	O
+acids	O
+-	O
+several	O
+Gly	O
+residues	O
+and	O
+an	O
+Asn	O
+residue	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Conserved	O
+Gly	O
+residues	O
+are	O
+a	O
+frequent	O
+theme	O
+in	O
+the	O
+organization	O
+of	O
+interacting	O
+transmembrane	O
+domains	O
+.	O
+
+Analysis	O
+of	O
+3D	O
+helix	O
+packing	O
+in	O
+polytopic	O
+membrane	O
+proteins	O
+reveals	O
+that	O
+Gly	O
+residues	O
+tend	O
+to	O
+localize	O
+in	O
+buried	O
+positions	O
+,	O
+especially	O
+at	O
+the	O
+helix	O
+-	O
+helix	O
+interfaces	O
+and	O
+helix	O
+crossing	O
+points	O
+[	O
+37	O
+,	O
+38	O
+]	O
+.	O
+
+Due	O
+to	O
+the	O
+absence	O
+of	O
+a	O
+side	O
+chain	O
+,	O
+Gly	O
+provides	O
+a	O
+flat	O
+surface	O
+for	O
+packing	O
+of	O
+a	O
+side	O
+chain	O
+from	O
+another	O
+residue	O
+,	O
+without	O
+loss	O
+of	O
+side	O
+-	O
+chain	O
+entropy	O
+upon	O
+interaction	O
+.	O
+
+The	O
+most	O
+common	O
+Gly	O
+-	O
+containing	O
+motif	O
+is	O
+GxxxG	O
+[	O
+39	O
+,	O
+40	O
+]	O
+.	O
+
+In	O
+glycophorin	O
+A	O
+(	O
+GpA	O
+)	O
+,	O
+the	O
+major	O
+glycoprotein	O
+in	O
+erythrocyte	O
+cell	O
+membranes	O
+,	O
+Gly79	O
+and	O
+Gly83	O
+are	O
+part	O
+of	O
+the	O
+LIxxGVxxGVxxT	O
+sequence	O
+that	O
+promotes	O
+homodimerization	O
+of	O
+parallel	O
+transmembrane	O
+alpha	O
+-	O
+helixes	O
+[	O
+41	O
+,	O
+42	O
+]	O
+.	O
+
+In	O
+the	O
+GpA	O
+dimerization	O
+motif	O
+,	O
+Gly	O
+residues	O
+allow	O
+for	O
+tight	O
+packing	O
+in	O
+the	O
+right	O
+-	O
+handed	O
+helical	O
+crossing	O
+[	O
+43	O
+]	O
+.	O
+
+There	O
+are	O
+also	O
+examples	O
+of	O
+left	O
+-	O
+handed	O
+helical	O
+crossing	O
+in	O
+the	O
+context	O
+of	O
+a	O
+GxxxG	O
+motif	O
+[	O
+44	O
+]	O
+.	O
+
+Other	O
+membrane	O
+proteins	O
+that	O
+use	O
+the	O
+GxxxG	O
+motif	O
+for	O
+homo	O
+-	O
+or	O
+heterodimerization	O
+include	O
+bacteriophage	B
+M13	I
+coat	O
+proteins	O
+[	O
+45	O
+]	O
+,	O
+yeast	B
+alpha	O
+factor	O
+receptor	O
+[	O
+46	O
+]	O
+,	O
+integrin	O
+alpha	O
+IIb	O
+subunit	O
+[	O
+47	O
+]	O
+,	O
+and	O
+ErbB1	O
+receptor	O
+tyrosine	O
+kinase	O
+[	O
+48	O
+]	O
+.	O
+
+Other	O
+small	O
+residues	O
+,	O
+such	O
+as	O
+Ala	O
+and	O
+Ser	O
+,	O
+can	O
+substitute	O
+for	O
+Gly	O
+in	O
+this	O
+motif	O
+[	O
+49	O
+]	O
+.	O
+
+A	O
+protein	O
+motif	O
+in	O
+which	O
+Gly	O
+residues	O
+are	O
+separated	O
+by	O
+6	O
+other	O
+residues	O
+(	O
+GG7	O
+)	O
+is	O
+also	O
+common	O
+in	O
+transmembrane	O
+helices	O
+,	O
+especially	O
+in	O
+transporter	O
+/	O
+channel	O
+-	O
+like	O
+membrane	O
+proteins	O
+[	O
+50	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+structural	O
+features	O
+associated	O
+with	O
+this	O
+motif	O
+are	O
+not	O
+well	O
+known	O
+.	O
+
+In	O
+particular	O
+,	O
+it	O
+is	O
+unclear	O
+whether	O
+left	O
+-	O
+handed	O
+GG7	O
+heptad	O
+repeat	O
+motif	O
+(	O
+as	O
+opposed	O
+to	O
+the	O
+"	O
+classic	O
+"	O
+right	O
+-	O
+handed	O
+GxxxG	O
+motif	O
+)	O
+can	O
+drive	O
+membrane	O
+helix	O
+association	O
+.	O
+
+In	O
+a	O
+recent	O
+work	O
+addressing	O
+this	O
+issue	O
+,	O
+Lear	O
+et	O
+al	O
+.	O
+
+[	O
+51	O
+]	O
+showed	O
+that	O
+a	O
+synthetic	O
+peptide	O
+containing	O
+Gly	O
+at	O
+heptad	O
+positions	O
+a	O
+and	O
+d	O
+could	O
+self	O
+-	O
+associate	O
+in	O
+vitro	O
+,	O
+likely	O
+in	O
+an	O
+antiparallel	O
+orientation	O
+.	O
+
+Heptad	O
+repeats	O
+containing	O
+conserved	O
+Gly	O
+residues	O
+occur	O
+in	O
+TM	O
+domains	O
+of	O
+alpha	O
+and	O
+beta	O
+chains	O
+of	O
+MHC	O
+class	O
+II	O
+proteins	O
+,	O
+and	O
+mutations	O
+of	O
+the	O
+Gly	O
+residues	O
+disrupt	O
+the	O
+alpha	O
+beta	O
+heterodimer	O
+[	O
+52	O
+]	O
+.	O
+
+These	O
+examples	O
+demonstrate	O
+that	O
+Gly	O
+-	O
+based	O
+heptad	O
+motifs	O
+may	O
+be	O
+used	O
+for	O
+both	O
+intra	O
+-	O
+and	O
+intermolecular	O
+associations	O
+.	O
+
+In	O
+this	O
+work	O
+,	O
+we	O
+identified	O
+a	O
+highly	O
+conserved	O
+GG7	O
+motif	O
+in	O
+the	O
+first	O
+two	O
+tetraspanin	O
+TM	O
+domains	O
+.	O
+
+The	O
+GG7	O
+sequence	O
+in	O
+tetraspanins	O
+is	O
+a	O
+part	O
+of	O
+a	O
+larger	O
+motif	O
+that	O
+also	O
+includes	O
+a	O
+conserved	O
+Asn	O
+residue	O
+in	O
+TM1	O
+(	O
+NGG7	O
+)	O
+and	O
+an	O
+Ala	O
+/	O
+Ser	O
+/	O
+Thr	O
+residue	O
+in	O
+TM2	O
+(	O
+GGA7	O
+)	O
+.	O
+
+The	O
+seven	O
+-	O
+residue	O
+periodicity	O
+of	O
+these	O
+motifs	O
+strongly	O
+suggests	O
+their	O
+involvement	O
+in	O
+left	O
+-	O
+handed	O
+coiled	O
+coil	O
+packing	O
+reminiscent	O
+of	O
+the	O
+leucine	O
+zipper	O
+,	O
+rather	O
+than	O
+right	O
+-	O
+handed	O
+packing	O
+of	O
+the	O
+GpA	O
+-	O
+like	O
+GxxxG	O
+motif	O
+.	O
+
+For	O
+antiparallel	O
+helices	O
+,	O
+the	O
+left	O
+-	O
+handed	O
+crossing	O
+is	O
+in	O
+fact	O
+predominant	O
+over	O
+the	O
+right	O
+-	O
+handed	O
+in	O
+known	O
+TM	O
+domain	O
+structures	O
+[	O
+44	O
+]	O
+.	O
+
+In	O
+our	O
+model	O
+,	O
+heptad	O
+Gly	O
+residues	O
+in	O
+NGG7	O
+and	O
+GGA7	O
+sequences	O
+provide	O
+specific	O
+packing	O
+between	O
+antiparallel	O
+tetraspanin	O
+TM1	O
+and	O
+TM2	O
+helices	O
+by	O
+allowing	O
+tight	O
+van	O
+der	O
+Waals	O
+interactions	O
+with	O
+large	O
+hydrophobic	O
+residues	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+Highly	O
+efficient	O
+packing	O
+of	O
+bulky	O
+side	O
+chains	O
+against	O
+glycine	O
+residues	O
+is	O
+observed	O
+in	O
+known	O
+transmembrane	O
+protein	O
+3D	O
+structures	O
+[	O
+38	O
+,	O
+53	O
+,	O
+54	O
+]	O
+.	O
+
+An	O
+example	O
+includes	O
+packing	O
+of	O
+helices	O
+M1	O
+and	O
+M2	O
+in	O
+potassium	O
+channel	O
+KcsA	O
+,	O
+where	O
+Val91	O
+in	O
+M2	O
+is	O
+paired	O
+with	O
+Gly43	O
+in	O
+M1	O
+,	O
+and	O
+Leu36	O
+in	O
+M1	O
+contacts	O
+Ala98	O
+and	O
+Gly99	O
+in	O
+helix	O
+M2	O
+[	O
+54	O
+,	O
+55	O
+]	O
+.	O
+
+In	O
+addition	O
+to	O
+facilitating	O
+helix	O
+-	O
+helix	O
+packing	O
+,	O
+Gly	O
+residues	O
+frequently	O
+provide	O
+additional	O
+C	O
+alpha	O
+H	O
+.	O
+.	O
+.	O
+O	O
+hydrogen	O
+bonds	O
+between	O
+two	O
+helices	O
+[	O
+44	O
+]	O
+.	O
+
+In	O
+our	O
+model	O
+,	O
+two	O
+C	O
+alpha	O
+-	O
+backbone	O
+carbonyl	O
+H	O
+-	O
+bonds	O
+are	O
+predicted	O
+-	O
+between	O
+residues	O
+Gly27	O
+-	O
+Gly67	O
+,	O
+and	O
+Trp22	O
+-	O
+Met70	O
+.	O
+
+Although	O
+polar	O
+and	O
+charged	O
+amino	O
+acid	O
+residues	O
+(	O
+such	O
+as	O
+Asn	O
+in	O
+the	O
+TM1	O
+heptad	O
+motif	O
+)	O
+are	O
+infrequent	O
+in	O
+transmembrane	O
+domains	O
+,	O
+they	O
+are	O
+functionally	O
+important	O
+.	O
+
+Polar	O
+residues	O
+such	O
+as	O
+glutamine	O
+,	O
+glutamic	O
+acid	O
+,	O
+aspartic	O
+acid	O
+and	O
+asparagine	O
+can	O
+promote	O
+strong	O
+oligomerization	O
+of	O
+model	O
+membrane	O
+-	O
+associated	O
+helices	O
+[	O
+56	O
+-	O
+58	O
+]	O
+.	O
+
+Ruan	O
+et	O
+al	O
+.	O
+
+[	O
+59	O
+]	O
+used	O
+asparagine	O
+scanning	O
+mutagenesis	O
+to	O
+probe	O
+the	O
+interface	O
+of	O
+self	O
+-	O
+associating	O
+polyleucine	O
+helices	O
+by	O
+detecting	O
+their	O
+enhanced	O
+self	O
+-	O
+interaction	O
+in	O
+vitro	O
+and	O
+in	O
+the	O
+E	B
+.	I
+coli	I
+-	O
+based	O
+ToxR	O
+assay	O
+.	O
+
+Thus	O
+,	O
+a	O
+hydrogen	O
+bond	O
+in	O
+an	O
+apolar	O
+environment	O
+can	O
+result	O
+in	O
+strong	O
+,	O
+though	O
+not	O
+necessarily	O
+specific	O
+,	O
+association	O
+of	O
+transmembrane	O
+helices	O
+.	O
+
+In	O
+fact	O
+,	O
+mutations	O
+to	O
+polar	O
+residues	O
+in	O
+transmembrane	O
+proteins	O
+are	O
+commonly	O
+associated	O
+with	O
+disease	O
+[	O
+60	O
+]	O
+.	O
+
+Because	O
+of	O
+this	O
+potential	O
+for	O
+non	O
+-	O
+specific	O
+interactions	O
+,	O
+polar	O
+residues	O
+tend	O
+to	O
+localize	O
+at	O
+buried	O
+positions	O
+in	O
+TM	O
+domains	O
+.	O
+
+In	O
+our	O
+case	O
+,	O
+the	O
+conserved	O
+Asn18	O
+residue	O
+in	O
+CD9	O
+is	O
+predicted	O
+to	O
+be	O
+a	O
+part	O
+of	O
+the	O
+TM1	O
+-	O
+TM2	O
+interface	O
+,	O
+though	O
+our	O
+model	O
+does	O
+not	O
+predict	O
+any	O
+electrostatic	O
+interaction	O
+between	O
+Asn18	O
+and	O
+TM2	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+Consistently	O
+,	O
+substitution	O
+such	O
+as	O
+Asn18Tyr	O
+(	O
+and	O
+Gly77Leu	O
+)	O
+in	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+protein	O
+was	O
+not	O
+destabilizing	O
+as	O
+analyzed	O
+by	O
+protein	O
+aggregation	O
+.	O
+
+Curiously	O
+,	O
+the	O
+full	O
+-	O
+length	O
+Asn18Ser	O
+CD9	O
+migrated	O
+slightly	O
+slower	O
+on	O
+SDS	O
+-	O
+PAGE	O
+gel	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+suggesting	O
+that	O
+Asn18	O
+does	O
+play	O
+a	O
+role	O
+in	O
+maintaining	O
+conformation	O
+of	O
+the	O
+molecule	O
+.	O
+
+The	O
+Asn18Cys	O
+single	O
+-	O
+cysteine	O
+mutant	O
+shows	O
+very	O
+little	O
+intermolecular	O
+cross	O
+-	O
+linking	O
+(	O
+Figure	O
+7A	O
+)	O
+,	O
+supporting	O
+the	O
+proposed	O
+location	O
+of	O
+this	O
+residue	O
+at	O
+the	O
+intramolecular	O
+interface	O
+.	O
+
+It	O
+is	O
+tempting	O
+to	O
+speculate	O
+that	O
+the	O
+"	O
+pocket	O
+"	O
+between	O
+TM1	O
+and	O
+TM2	O
+lined	O
+by	O
+Asn18	O
+and	O
+Gly77	O
+might	O
+be	O
+important	O
+for	O
+accommodating	O
+palmitate	O
+moieties	O
+that	O
+target	O
+Cys78	O
+and	O
+Cys79	O
+residues	O
+,	O
+and	O
+/	O
+or	O
+important	O
+for	O
+access	O
+by	O
+the	O
+putative	O
+palmitoyl	O
+transferase	O
+to	O
+those	O
+residues	O
+.	O
+
+Understanding	O
+the	O
+exact	O
+role	O
+of	O
+these	O
+highly	O
+conserved	O
+Asn18	O
+and	O
+Gly77	O
+residues	O
+in	O
+tetraspanins	O
+awaits	O
+further	O
+investigation	O
+.	O
+
+In	O
+summary	O
+,	O
+we	O
+identified	O
+conserved	O
+glycine	O
+residues	O
+of	O
+TM1	O
+and	O
+TM2	O
+of	O
+tetraspanins	O
+as	O
+key	O
+elements	O
+required	O
+for	O
+intramolecular	O
+packing	O
+.	O
+
+Mutations	O
+of	O
+these	O
+key	O
+residues	O
+(	O
+Gly25	O
+,	O
+Gly32	O
+,	O
+Gly67	O
+and	O
+Gly74	O
+in	O
+CD9	O
+)	O
+resulted	O
+in	O
+protein	O
+destabilization	O
+and	O
+aggregation	O
+.	O
+
+There	O
+is	O
+ample	O
+evidence	O
+in	O
+the	O
+literature	O
+for	O
+mutations	O
+in	O
+transmembrane	O
+proteins	O
+that	O
+lead	O
+to	O
+protein	O
+destabilization	O
+,	O
+misassembly	O
+and	O
+pathologic	O
+conditions	O
+[	O
+61	O
+]	O
+.	O
+
+Thus	O
+,	O
+we	O
+have	O
+identified	O
+conserved	O
+heptad	O
+Gly	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+of	O
+tetraspanins	O
+as	O
+plausible	O
+targets	O
+of	O
+destabilizing	O
+mutations	O
+with	O
+potential	O
+functional	O
+consequences	O
+.	O
+
+Intermolecular	O
+interactions	O
+in	O
+tetraspanins	O
+
+Tetraspanin	O
+CD9	O
+forms	O
+mostly	O
+homodimers	O
+,	O
+but	O
+also	O
+a	O
+low	O
+level	O
+of	O
+heterodimers	O
+with	O
+CD81	O
+and	O
+CD151	O
+[	O
+25	O
+]	O
+.	O
+
+Thus	O
+,	O
+mapping	O
+the	O
+dimerization	O
+interface	O
+is	O
+an	O
+important	O
+next	O
+step	O
+in	O
+structure	O
+-	O
+function	O
+analysis	O
+of	O
+tetraspanins	O
+.	O
+
+Disulfide	O
+-	O
+mediated	O
+cross	O
+-	O
+linking	O
+,	O
+often	O
+in	O
+combination	O
+with	O
+cysteine	O
+-	O
+scanning	O
+mutagenesis	O
+,	O
+is	O
+a	O
+common	O
+strategy	O
+to	O
+probe	O
+oligomerization	O
+or	O
+intersubunit	O
+interactions	O
+of	O
+transmembrane	O
+proteins	O
+such	O
+as	O
+histidine	O
+kinase	O
+EnvZ	O
+[	O
+62	O
+]	O
+,	O
+M	O
+(	O
+3	O
+)	O
+muscarinic	O
+acetylcholine	O
+receptor	O
+[	O
+63	O
+]	O
+,	O
+E	B
+.	I
+coli	I
+lactose	O
+permease	O
+[	O
+64	O
+]	O
+,	O
+synaptobrevin	O
+[	O
+65	O
+]	O
+,	O
+integrins	O
+[	O
+66	O
+]	O
+and	O
+many	O
+others	O
+.	O
+
+In	O
+tetraspanins	O
+such	O
+as	O
+CD9	O
+,	O
+membrane	O
+-	O
+proximal	O
+cysteine	O
+residues	O
+are	O
+especially	O
+useful	O
+targets	O
+for	O
+disulfide	O
+trapping	O
+,	O
+as	O
+their	O
+linkage	O
+can	O
+be	O
+enhanced	O
+by	O
+pre	O
+-	O
+treating	O
+cells	O
+with	O
+2	O
+-	O
+BP	O
+.	O
+
+While	O
+the	O
+ability	O
+of	O
+wild	O
+-	O
+type	O
+cysteines	O
+in	O
+CD9	O
+to	O
+be	O
+cross	O
+-	O
+linked	O
+may	O
+indicate	O
+that	O
+they	O
+are	O
+close	O
+to	O
+the	O
+dimerization	O
+interface	O
+,	O
+more	O
+precise	O
+mapping	O
+was	O
+achieved	O
+here	O
+using	O
+cysteine	O
+-	O
+scanning	O
+mutagenesis	O
+.	O
+
+Our	O
+data	O
+clearly	O
+identify	O
+regions	O
+,	O
+near	O
+the	O
+cytoplasmic	O
+face	O
+of	O
+TM1	O
+and	O
+TM2	O
+,	O
+important	O
+for	O
+dimerization	O
+.	O
+
+Intermolecular	O
+zero	O
+-	O
+length	O
+cross	O
+-	O
+linking	O
+was	O
+highest	O
+when	O
+single	O
+cysteines	O
+were	O
+placed	O
+in	O
+positions	O
+14	O
+,	O
+17	O
+,	O
+77	O
+,	O
+80	O
+and	O
+81	O
+in	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+molecule	O
+,	O
+or	O
+at	O
+positions	O
+77	O
+,	O
+80	O
+or	O
+81	O
+in	O
+the	O
+full	O
+-	O
+length	O
+CD9	O
+protein	O
+.	O
+
+Positions	O
+14	O
+,	O
+17	O
+and	O
+80	O
+are	O
+distinct	O
+from	O
+the	O
+intramolecular	O
+interface	O
+and	O
+are	O
+on	O
+the	O
+same	O
+side	O
+of	O
+the	O
+TM1	O
+-	O
+TM2	O
+pair	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+Thus	O
+,	O
+they	O
+are	O
+well	O
+-	O
+positioned	O
+to	O
+participate	O
+in	O
+an	O
+interaction	O
+with	O
+another	O
+molecule	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+,	O
+the	O
+model	O
+predicts	O
+that	O
+wild	O
+-	O
+type	O
+cysteines	O
+(	O
+Cys78	O
+,	O
+79	O
+)	O
+,	O
+which	O
+do	O
+not	O
+yield	O
+very	O
+efficient	O
+zero	O
+-	O
+length	O
+cross	O
+-	O
+linking	O
+,	O
+are	O
+on	O
+the	O
+other	O
+side	O
+of	O
+TM1	O
+-	O
+TM2	O
+pair	O
+.	O
+
+While	O
+using	O
+the	O
+cysteine	O
+at	O
+position	O
+80	O
+as	O
+the	O
+dimeric	O
+interface	O
+probe	O
+,	O
+mutations	O
+of	O
+conserved	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+(	O
+especially	O
+Gly32	O
+and	O
+Gly67	O
+to	O
+Leu	O
+)	O
+clearly	O
+reduced	O
+intermolecular	O
+cross	O
+-	O
+linking	O
+.	O
+
+We	O
+do	O
+not	O
+suggest	O
+that	O
+those	O
+residues	O
+are	O
+directly	O
+involved	O
+in	O
+intermolecular	O
+interaction	O
+.	O
+
+Rather	O
+,	O
+we	O
+propose	O
+that	O
+destabilization	O
+of	O
+the	O
+intramolecular	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+by	O
+Gly	O
+to	O
+Leu	O
+substitutions	O
+(	O
+discussed	O
+above	O
+)	O
+causes	O
+an	O
+overall	O
+conformational	O
+change	O
+that	O
+reduces	O
+dimer	O
+formation	O
+.	O
+
+An	O
+Ala81Leu	O
+mutation	O
+did	O
+not	O
+reduce	O
+cross	O
+-	O
+linking	O
+via	O
+Cys80	O
+,	O
+even	O
+though	O
+single	O
+-	O
+cysteine	O
+Ala81Cys	O
+molecules	O
+themselves	O
+produced	O
+a	O
+high	O
+level	O
+of	O
+cross	O
+-	O
+linking	O
+.	O
+
+These	O
+results	O
+,	O
+together	O
+with	O
+data	O
+on	O
+Gly32Leu	O
+and	O
+Gly67Leu	O
+mutations	O
+,	O
+are	O
+consistent	O
+with	O
+our	O
+model	O
+predicting	O
+that	O
+helices	O
+1	O
+and	O
+2	O
+interact	O
+more	O
+tightly	O
+near	O
+the	O
+extracellular	O
+end	O
+and	O
+less	O
+at	O
+the	O
+cytoplasmic	O
+end	O
+.	O
+
+This	O
+would	O
+give	O
+more	O
+flexibility	O
+to	O
+a	O
+cysteine	O
+at	O
+position	O
+81	O
+and	O
+also	O
+limit	O
+the	O
+effect	O
+of	O
+an	O
+Ala81Leu	O
+mutation	O
+.	O
+
+Location	O
+of	O
+this	O
+residue	O
+at	O
+the	O
+membrane	O
+/	O
+cytoplasmic	O
+border	O
+could	O
+also	O
+make	O
+it	O
+more	O
+accessible	O
+to	O
+CuP	O
+reagent	O
+as	O
+compared	O
+to	O
+residues	O
+buried	O
+in	O
+TM	O
+domain	O
+,	O
+thus	O
+elevating	O
+the	O
+efficiency	O
+of	O
+disulfide	O
+formation	O
+of	O
+the	O
+Ala81Cys	O
+mutant	O
+.	O
+
+Multiple	O
+interfaces	O
+in	O
+tetraspanin	O
+molecules	O
+
+In	O
+the	O
+full	O
+-	O
+length	O
+CD9	O
+molecules	O
+,	O
+the	O
+3	O
+C	O
+-	O
+terminal	O
+cysteines	O
+(	O
+Cys87	O
+,	O
+218	O
+and	O
+219	O
+)	O
+located	O
+at	O
+or	O
+in	O
+TM3	O
+and	O
+TM4	O
+promoted	O
+efficient	O
+dimer	O
+and	O
+even	O
+more	O
+efficient	O
+oligomer	O
+formation	O
+compared	O
+to	O
+the	O
+3	O
+N	O
+-	O
+terminal	O
+cysteines	O
+(	O
+Figure	O
+9	O
+)	O
+.	O
+
+Cys87	O
+alone	O
+can	O
+be	O
+used	O
+to	O
+capture	O
+CD9	O
+dimers	O
+[	O
+25	O
+]	O
+.	O
+
+These	O
+results	O
+suggest	O
+the	O
+existence	O
+of	O
+two	O
+dimeric	O
+interfaces	O
+in	O
+CD9	O
+molecule	O
+-	O
+the	O
+TM	O
+1	O
+-	O
+2	O
+/	O
+1	O
+-	O
+2	O
+interface	O
+and	O
+the	O
+TM	O
+3	O
+-	O
+4	O
+/	O
+3	O
+-	O
+4	O
+interface	O
+(	O
+Figure	O
+10	O
+)	O
+.	O
+
+In	O
+a	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+molecule	O
+,	O
+the	O
+destabilization	O
+of	O
+1	O
+-	O
+2	O
+interaction	O
+,	O
+e	O
+.	O
+g	O
+.	O
+by	O
+Gly	O
+-	O
+-	O
+>	O
+Leu	O
+mutations	O
+,	O
+would	O
+affect	O
+the	O
+1	O
+-	O
+2	O
+/	O
+1	O
+-	O
+2	O
+interface	O
+,	O
+as	O
+discussed	O
+above	O
+.	O
+
+However	O
+,	O
+these	O
+mutations	O
+would	O
+not	O
+interfere	O
+with	O
+the	O
+3	O
+-	O
+4	O
+/	O
+3	O
+-	O
+4	O
+interface	O
+in	O
+a	O
+full	O
+-	O
+length	O
+molecule	O
+,	O
+which	O
+includes	O
+Cys87	O
+,	O
+218	O
+and	O
+219	O
+.	O
+
+Thus	O
+,	O
+cross	O
+-	O
+linking	O
+of	O
+full	O
+-	O
+length	O
+molecules	O
+,	O
+containing	O
+all	O
+6	O
+cysteine	O
+residues	O
+,	O
+would	O
+be	O
+unaffected	O
+,	O
+as	O
+seen	O
+in	O
+Figure	O
+8C	O
+.	O
+
+Furthermore	O
+,	O
+wild	O
+-	O
+type	O
+Cys9	O
+,	O
+Cys78	O
+and	O
+Cys79	O
+are	O
+apparently	O
+not	O
+at	O
+the	O
+primary	O
+1	O
+-	O
+2	O
+/	O
+1	O
+-	O
+2	O
+interface	O
+.	O
+
+Their	O
+relative	O
+inefficiency	O
+in	O
+cross	O
+-	O
+linking	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+protein	O
+likely	O
+reflects	O
+weak	O
+secondary	O
+contacts	O
+between	O
+the	O
+molecules	O
+,	O
+or	O
+possibly	O
+random	O
+collision	O
+events	O
+.	O
+
+Such	O
+events	O
+should	O
+be	O
+independent	O
+of	O
+mutations	O
+in	O
+the	O
+conserved	O
+Gly	O
+residues	O
+in	O
+TM1	O
+and	O
+TM2	O
+,	O
+as	O
+was	O
+demonstrated	O
+in	O
+Figure	O
+8B	O
+.	O
+
+The	O
+potential	O
+existence	O
+of	O
+two	O
+interfaces	O
+in	O
+tetraspanin	O
+molecules	O
+,	O
+1	O
+-	O
+2	O
+/	O
+1	O
+-	O
+2	O
+and	O
+3	O
+-	O
+4	O
+/	O
+3	O
+-	O
+4	O
+,	O
+should	O
+provide	O
+enhanced	O
+flexibility	O
+for	O
+forming	O
+additional	O
+intermolecular	O
+contacts	O
+.	O
+
+Current	O
+understanding	O
+of	O
+tetraspanin	O
+microdomains	O
+assumes	O
+a	O
+few	O
+strong	O
+,	O
+primary	O
+homotypic	O
+and	O
+heterotypic	O
+tetraspanin	O
+complexes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+CD9	O
+-	O
+CD9	O
+,	O
+CD9	O
+-	O
+CD81	O
+,	O
+CD151	O
+-	O
+alpha	O
+3	O
+integrin	O
+,	O
+CD81	O
+-	O
+EWI2	O
+)	O
+that	O
+help	O
+bring	O
+together	O
+various	O
+other	O
+proteins	O
+,	O
+forming	O
+secondary	O
+-	O
+type	O
+associations	O
+.	O
+
+Such	O
+properties	O
+of	O
+tetraspanins	O
+may	O
+bring	O
+signaling	O
+molecules	O
+such	O
+as	O
+protein	O
+kinase	O
+C	O
+or	O
+phosphatidylinositol	O
+4	O
+-	O
+kinase	O
+to	O
+the	O
+vicinity	O
+of	O
+integrins	O
+[	O
+67	O
+,	O
+68	O
+]	O
+.	O
+
+The	O
+organization	O
+of	O
+the	O
+TM3	O
+domain	O
+points	O
+to	O
+a	O
+potential	O
+role	O
+in	O
+protein	O
+-	O
+protein	O
+interactions	O
+.	O
+
+A	O
+motif	O
+of	O
+Leu	O
+-	O
+Leu	O
+-	O
+Glu	O
+(	O
+Gln	O
+)	O
+spaced	O
+7	O
+residues	O
+apart	O
+(	O
+heptad	O
+positions	O
+a	O
+)	O
+,	O
+with	O
+highly	O
+conserved	O
+residues	O
+in	O
+two	O
+consecutive	O
+positions	O
+d	O
+,	O
+poses	O
+as	O
+a	O
+likely	O
+interaction	O
+module	O
+.	O
+
+If	O
+responsible	O
+for	O
+heterologous	O
+protein	O
+-	O
+protein	O
+interactions	O
+,	O
+it	O
+would	O
+form	O
+another	O
+distinct	O
+interface	O
+of	O
+tetraspanin	O
+molecule	O
+.	O
+
+Our	O
+preliminary	O
+data	O
+indicate	O
+that	O
+replacing	O
+the	O
+Leu	O
+and	O
+Glu	O
+residues	O
+in	O
+TM3	O
+of	O
+CD9	O
+with	O
+Ala	O
+has	O
+no	O
+effect	O
+on	O
+cell	O
+surface	O
+expression	O
+of	O
+the	O
+protein	O
+and	O
+its	O
+dimerization	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+It	O
+remains	O
+to	O
+be	O
+tested	O
+if	O
+interactions	O
+with	O
+other	O
+proteins	O
+will	O
+be	O
+affected	O
+.	O
+
+Similarly	O
+,	O
+the	O
+TM4	O
+domain	O
+may	O
+provide	O
+additional	O
+contributions	O
+to	O
+lateral	O
+tetraspanin	O
+associations	O
+.	O
+
+Much	O
+higher	O
+sequence	O
+variability	O
+,	O
+and	O
+the	O
+lack	O
+of	O
+a	O
+distinct	O
+heptad	O
+pattern	O
+suggests	O
+that	O
+TM4	O
+is	O
+a	O
+major	O
+contributor	O
+to	O
+diversity	O
+among	O
+tetraspanin	O
+complexes	O
+.	O
+
+Structure	O
+-	O
+function	O
+analysis	O
+of	O
+TM3	O
+and	O
+TM4	O
+domains	O
+in	O
+tetraspanins	O
+is	O
+the	O
+subject	O
+of	O
+ongoing	O
+investigation	O
+.	O
+
+Conclusion	O
+
+We	O
+have	O
+defined	O
+the	O
+TM1	O
+-	O
+TM2	O
+intramolecular	O
+interface	O
+in	O
+tetraspanin	O
+CD9	O
+,	O
+providing	O
+evidence	O
+for	O
+glycines	O
+(	O
+Gly25	O
+and	O
+Gly32	O
+in	O
+TM1	O
+,	O
+Gly67	O
+and	O
+Gly74	O
+in	O
+TM2	O
+)	O
+packing	O
+against	O
+apposing	O
+bulky	O
+aliphatic	O
+residues	O
+.	O
+
+Second	O
+,	O
+we	O
+mapped	O
+an	O
+intermolecular	O
+CD9	O
+interface	O
+(	O
+involved	O
+in	O
+CD9	O
+homodimer	O
+formation	O
+)	O
+to	O
+the	O
+vicinity	O
+of	O
+residues	O
+Leu14	O
+and	O
+Phe17	O
+in	O
+TM1	O
+and	O
+Gly77	O
+,	O
+Gly80	O
+and	O
+Ala81	O
+in	O
+TM2	O
+.	O
+
+Finally	O
+,	O
+we	O
+provide	O
+preliminary	O
+evidence	O
+that	O
+TM3	O
+and	O
+TM4	O
+in	O
+CD9	O
+may	O
+contribute	O
+to	O
+a	O
+second	O
+intermolecular	O
+interface	O
+.	O
+
+Key	O
+CD9	O
+residues	O
+involved	O
+in	O
+intra	O
+-	O
+and	O
+intermolecular	O
+interactions	O
+are	O
+highly	O
+conserved	O
+throughout	O
+the	O
+tetraspanin	O
+family	O
+,	O
+thus	O
+suggesting	O
+that	O
+our	O
+findings	O
+will	O
+apply	O
+to	O
+most	O
+tetraspanins	O
+.	O
+
+Methods	O
+
+Materials	O
+
+Cell	O
+culture	O
+reagents	O
+were	O
+from	O
+Invitrogen	O
+(	O
+Carlsbad	O
+,	O
+CA	O
+)	O
+.	O
+
+2	O
+-	O
+bromopalmitate	O
+was	O
+from	O
+Fluka	O
+(	O
+Milwaukee	O
+,	O
+WI	O
+)	O
+,	O
+N	O
+-	O
+ethylmaleimide	O
+(	O
+NEM	O
+)	O
+and	O
+1	O
+,	O
+10	O
+-	O
+phenanthroline	O
+were	O
+from	O
+Sigma	O
+-	O
+Aldrich	O
+(	O
+St	O
+.	O
+Louis	O
+,	O
+MO	O
+)	O
+,	O
+and	O
+chemical	O
+cross	O
+-	O
+linkers	O
+dithio	O
+-	O
+bis	O
+-	O
+maleimidoethane	O
+(	O
+DTME	O
+)	O
+and	O
+1	O
+,	O
+4	O
+-	O
+Bis	O
+-	O
+maleimidobutane	O
+(	O
+BMB	O
+)	O
+were	O
+purchased	O
+from	O
+Pierce	O
+Endogen	O
+(	O
+Rockford	O
+,	O
+IL	O
+)	O
+.	O
+
+Triton	O
+X	O
+-	O
+100	O
+,	O
+protease	O
+inhibitor	O
+cocktail	O
+and	O
+FuGENE	O
+6	O
+transfection	O
+reagent	O
+were	O
+obtained	O
+from	O
+Roche	O
+(	O
+Indianapolis	O
+,	O
+IN	O
+)	O
+.	O
+
+Restriction	O
+endonucleases	O
+and	O
+Pfu	O
+DNA	O
+polymerase	O
+were	O
+obtained	O
+New	O
+England	O
+Biolabs	O
+(	O
+Beverly	O
+,	O
+MA	O
+)	O
+and	O
+Stratagene	O
+(	O
+Carlsbad	O
+,	O
+CA	O
+)	O
+,	O
+respectively	O
+.	O
+
+All	O
+other	O
+chemicals	O
+were	O
+purchased	O
+from	O
+Sigma	O
+-	O
+Aldrich	O
+or	O
+Fisher	O
+Scientific	O
+(	O
+Pittsburg	O
+,	O
+PA	O
+)	O
+.	O
+
+Sequence	O
+analysis	O
+
+Tetraspanin	O
+sequences	O
+were	O
+obtained	O
+from	O
+SWISS	O
+-	O
+PROT	O
+and	O
+GenBank	O
+databases	O
+.	O
+
+Locus	O
+designations	O
+,	O
+accession	O
+numbers	O
+and	O
+the	O
+most	O
+commonly	O
+used	O
+protein	O
+names	O
+are	O
+summarized	O
+in	O
+Tables	O
+1	O
+and	O
+2	O
+.	O
+
+TM	O
+segments	O
+were	O
+delineated	O
+by	O
+inspection	O
+of	O
+hydrophobicity	O
+profiles	O
+,	O
+using	O
+database	O
+annotations	O
+and	O
+previous	O
+analyses	O
+of	O
+TM	O
+sequences	O
+as	O
+a	O
+guide	O
+(	O
+[	O
+28	O
+]	O
+,	O
+M	O
+.	O
+Hemler	O
+,	O
+unpublished	O
+)	O
+,	O
+and	O
+aligned	O
+manually	O
+.	O
+
+Residue	O
+numbers	O
+in	O
+human	B
+CD9	O
+sequence	O
+are	O
+used	O
+a	O
+reference	O
+point	O
+throughout	O
+the	O
+study	O
+.	O
+
+DNA	O
+cloning	O
+and	O
+mutagenesis	O
+
+Sequence	O
+encoding	O
+CD9	O
+protein	O
+was	O
+cloned	O
+into	O
+vector	O
+pcDNA3	O
+(	O
+Invitrogen	O
+,	O
+Carlsbad	O
+,	O
+CA	O
+)	O
+and	O
+pEGFP	O
+-	O
+N1	O
+(	O
+Clontech	O
+,	O
+Palo	O
+Alto	O
+,	O
+CA	O
+)	O
+,	O
+for	O
+expression	O
+of	O
+untagged	O
+and	O
+C	O
+-	O
+terminally	O
+GFP	O
+-	O
+tagged	O
+CD9	O
+,	O
+respectively	O
+.	O
+
+pEGFP	O
+-	O
+N1	O
+encoding	O
+CD9	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+fusion	O
+protein	O
+was	O
+constructed	O
+by	O
+subcloning	O
+DNA	O
+for	O
+residues	O
+1	O
+-	O
+83	O
+of	O
+CD9	O
+into	O
+HindIII	O
+and	O
+PstI	O
+sites	O
+of	O
+the	O
+vector	O
+;	O
+to	O
+introduce	O
+the	O
+PstI	O
+site	O
+,	O
+codon	O
+GTG	O
+for	O
+Val82	O
+was	O
+changed	O
+to	O
+CTG	O
+(	O
+coding	O
+for	O
+Ala	O
+)	O
+.	O
+
+In	O
+the	O
+resulting	O
+fusion	O
+protein	O
+,	O
+there	O
+is	O
+a	O
+13	O
+-	O
+amino	O
+acid	O
+linker	O
+(	O
+with	O
+no	O
+cysteines	O
+)	O
+between	O
+CD9	O
+and	O
+GFP	O
+.	O
+
+To	O
+minimize	O
+the	O
+low	O
+inherent	O
+ability	O
+of	O
+GFP	O
+to	O
+homodimerize	O
+,	O
+which	O
+could	O
+potentially	O
+influence	O
+the	O
+results	O
+of	O
+CD9	O
+cross	O
+-	O
+linking	O
+,	O
+we	O
+used	O
+a	O
+monomeric	O
+GFP	O
+mutant	O
+,	O
+Leu221	O
+-	O
+-	O
+>	O
+Lys	O
+[	O
+34	O
+]	O
+,	O
+for	O
+cross	O
+-	O
+linking	O
+experiments	O
+.	O
+
+Mutations	O
+were	O
+introduced	O
+in	O
+full	O
+-	O
+length	O
+and	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+CD9	O
+proteins	O
+by	O
+a	O
+PCR	O
+-	O
+based	O
+strategy	O
+using	O
+mutagenic	O
+primers	O
+and	O
+Pfu	O
+DNA	O
+polymerase	O
+.	O
+
+All	O
+mutations	O
+were	O
+confirmed	O
+by	O
+DNA	O
+sequencing	O
+.	O
+
+Protein	O
+expression	O
+,	O
+microscopy	O
+,	O
+cysteine	O
+disulfide	O
+cross	O
+-	O
+linking	O
+and	O
+Western	O
+blotting	O
+
+DNA	O
+constructs	O
+encoding	O
+TM	O
+(	O
+1	O
++	O
+2	O
+)	O
+-	O
+GFP	O
+or	O
+full	O
+-	O
+length	O
+CD9	O
+proteins	O
+were	O
+transfected	O
+into	O
+human	B
+rhabdomyosarcoma	O
+RD	O
+cells	O
+using	O
+the	O
+FuGENE	O
+6	O
+reagent	O
+.	O
+
+Cells	O
+expressing	O
+GFP	O
+fusion	O
+proteins	O
+were	O
+analysed	O
+by	O
+fluorescence	O
+microscopy	O
+18	O
+-	O
+28	O
+hours	O
+post	O
+-	O
+transfection	O
+.	O
+
+Images	O
+were	O
+captured	O
+using	O
+Spot	O
+1	O
+.	O
+4	O
+.	O
+0	O
+camera	O
+(	O
+Diagnostic	O
+Instruments	O
+,	O
+Sterling	O
+Heights	O
+,	O
+MI	O
+)	O
+attached	O
+to	O
+Nikon	O
+Eclipse	O
+TE300	O
+microscope	O
+.	O
+
+For	O
+experiments	O
+involving	O
+cysteine	O
+-	O
+mediated	O
+cross	O
+-	O
+linking	O
+,	O
+cells	O
+were	O
+treated	O
+with	O
+50	O
+mu	O
+M	O
+2	O
+-	O
+BP	O
+starting	O
+24	O
+-	O
+26	O
+hours	O
+post	O
+-	O
+transfection	O
+and	O
+continuing	O
+for	O
+16	O
+-	O
+18	O
+hours	O
+.	O
+
+Cross	O
+-	O
+linking	O
+was	O
+carried	O
+out	O
+by	O
+incubating	O
+cells	O
+in	O
+HBSM	O
+buffer	O
+(	O
+25	O
+mM	O
+Hepes	O
+-	O
+NaOH	O
+,	O
+pH	O
+7	O
+.	O
+2	O
+,	O
+150	O
+mM	O
+NaCl	O
+,	O
+2	O
+mM	O
+MgCl2	O
+)	O
+containing	O
+either	O
+a	O
+)	O
+0	O
+.	O
+6	O
+mM	O
+CuSO4	O
+and	O
+1	O
+.	O
+8	O
+mM	O
+1	O
+,	O
+10	O
+-	O
+phenanthroline	O
+(	O
+CuP	O
+complex	O
+)	O
+or	O
+b	O
+)	O
+0	O
+.	O
+2	O
+mg	O
+/	O
+ml	O
+homobifunctional	O
+cysteine	O
+-	O
+reactive	O
+cross	O
+-	O
+linker	O
+(	O
+e	O
+.	O
+g	O
+.	O
+DTME	O
+)	O
+,	O
+diluted	O
+from	O
+fresh	O
+10	O
+mg	O
+/	O
+ml	O
+solution	O
+in	O
+DMSO	O
+.	O
+
+After	O
+incubation	O
+for	O
+10	O
+-	O
+15	O
+minutes	O
+(	O
+with	O
+CuP	O
+)	O
+or	O
+30	O
+-	O
+45	O
+minutes	O
+(	O
+with	O
+cross	O
+-	O
+linker	O
+)	O
+,	O
+cells	O
+were	O
+washed	O
+twice	O
+for	O
+10	O
+minutes	O
+with	O
+HBSM	O
+containing	O
+10	O
+mM	O
+NEM	O
+to	O
+block	O
+residual	O
+free	O
+cysteines	O
+.	O
+
+Cells	O
+were	O
+lysed	O
+in	O
+HBSM	O
+containing	O
+1	O
+%	O
+Triton	O
+X	O
+-	O
+100	O
+,	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+and	O
+a	O
+cocktail	O
+of	O
+protease	O
+inhibitors	O
+with	O
+1	O
+mM	O
+EDTA	O
+at	O
+4	O
+degrees	O
+C	O
+for	O
+45	O
+-	O
+60	O
+minutes	O
+.	O
+
+Cell	O
+lysate	O
+was	O
+clarified	O
+by	O
+centrifugation	O
+at	O
+14	O
+,	O
+000	O
+x	O
+g	O
+for	O
+15	O
+minutes	O
+,	O
+an	O
+aliquot	O
+was	O
+removed	O
+,	O
+and	O
+proteins	O
+from	O
+it	O
+were	O
+precipitated	O
+by	O
+addition	O
+of	O
+trichloroacetic	O
+acid	O
+to	O
+10	O
+%	O
+on	O
+ice	O
+followed	O
+by	O
+centrifugation	O
+at	O
+14	O
+,	O
+000	O
+x	O
+g	O
+for	O
+10	O
+minutes	O
+.	O
+
+After	O
+two	O
+washes	O
+with	O
+ice	O
+-	O
+cold	O
+acetone	O
+,	O
+protein	O
+pellet	O
+was	O
+solubilized	O
+in	O
+SDS	O
+-	O
+PAGE	O
+sample	O
+buffer	O
+without	O
+a	O
+reducing	O
+agent	O
+(	O
+50	O
+mM	O
+Tris	O
+-	O
+HCl	O
+,	O
+pH	O
+6	O
+.	O
+8	O
+,	O
+1	O
+%	O
+SDS	O
+,	O
+8	O
+%	O
+glycerol	O
+)	O
+.	O
+
+In	O
+some	O
+experiments	O
+,	O
+CD9	O
+protein	O
+was	O
+immunoprecipitated	O
+using	O
+monoclonal	O
+antibody	O
+Alb6	O
+(	O
+Immunotech	O
+,	O
+Marseille	O
+,	O
+France	O
+)	O
+.	O
+
+Proteins	O
+were	O
+separated	O
+by	O
+SDS	O
+-	O
+PAGE	O
+and	O
+analyzed	O
+by	O
+Western	O
+blotting	O
+using	O
+monoclonal	O
+antibody	O
+JL	O
+-	O
+8	O
+(	O
+Clontech	O
+)	O
+for	O
+GFP	O
+or	O
+Alb6	O
+for	O
+CD9	O
+.	O
+
+Bands	O
+from	O
+X	O
+-	O
+ray	O
+films	O
+were	O
+quantitated	O
+using	O
+GeneTools	O
+(	O
+TM	O
+)	O
+software	O
+from	O
+Syngene	O
+(	O
+Frederick	O
+,	O
+MD	O
+)	O
+.	O
+
+Modeling	O
+of	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+
+An	O
+atomic	O
+model	O
+of	O
+the	O
+CD9	O
+TM1	O
+-	O
+TM2	O
+dimer	O
+was	O
+constructed	O
+with	O
+a	O
+Monte	O
+Carlo	O
+-	O
+simulated	O
+annealing	O
+(	O
+MCSA	O
+)	O
+algorithm	O
+[	O
+69	O
+]	O
+.	O
+
+Two	O
+idealized	O
+alpha	O
+-	O
+helices	O
+corresponding	O
+to	O
+TM1	O
+residues	O
+Tyr12	O
+through	O
+Leu35	O
+and	O
+TM2	O
+residues	O
+Gly59	O
+through	O
+Val82	O
+were	O
+docked	O
+with	O
+six	O
+orthogonal	O
+parameters	O
+:	O
+three	O
+rigid	O
+body	O
+translations	O
+and	O
+three	O
+rotations	O
+.	O
+
+During	O
+each	O
+step	O
+of	O
+a	O
+MCSA	O
+cycle	O
+,	O
+there	O
+was	O
+an	O
+equal	O
+probability	O
+of	O
+changing	O
+either	O
+one	O
+parameter	O
+or	O
+all	O
+six	O
+parameters	O
+to	O
+random	O
+values	O
+.	O
+
+A	O
+conformation	O
+'	O
+s	O
+energy	O
+was	O
+calculated	O
+in	O
+vacuo	O
+with	O
+the	O
+AMBER	O
+united	O
+-	O
+atom	O
+force	O
+field	O
+for	O
+van	O
+der	O
+Waals	O
+interactions	O
+[	O
+70	O
+]	O
+.	O
+
+The	O
+van	O
+der	O
+Waals	O
+term	O
+was	O
+modified	O
+as	O
+described	O
+by	O
+Kuhlman	O
+and	O
+Baker	O
+[	O
+71	O
+]	O
+.	O
+
+If	O
+a	O
+structure	O
+had	O
+favorable	O
+dimerization	O
+energy	O
+,	O
+the	O
+energies	O
+of	O
+select	O
+mutants	O
+were	O
+calculated	O
+.	O
+
+Structures	O
+were	O
+selected	O
+with	O
+a	O
+novel	O
+scoring	O
+function	O
+that	O
+maximizes	O
+the	O
+Boltzmann	O
+probability	O
+of	O
+dimerization	O
+for	O
+silent	O
+mutations	O
+while	O
+minimizing	O
+the	O
+probability	O
+for	O
+disruptive	O
+mutations	O
+.	O
+
+Asn18Ser	O
+,	O
+Gly77Leu	O
+,	O
+and	O
+Gly80Leu	O
+were	O
+scored	O
+as	O
+silent	O
+mutations	O
+while	O
+Gly25Leu	O
+,	O
+Gly32Leu	O
+,	O
+Gly67Leu	O
+,	O
+and	O
+Gly74Leu	O
+were	O
+considered	O
+to	O
+be	O
+disruptive	O
+.	O
+
+Each	O
+MCSA	O
+cycle	O
+consisted	O
+of	O
+50	O
+,	O
+000	O
+steps	O
+with	O
+an	O
+exponential	O
+temperature	O
+decay	O
+from	O
+10	O
+,	O
+000	O
+to	O
+10	O
+K	O
+.	O
+
+Ten	O
+MCSA	O
+cycles	O
+through	O
+global	O
+sample	O
+space	O
+were	O
+used	O
+to	O
+restrict	O
+the	O
+search	O
+area	O
+.	O
+
+Parameters	O
+were	O
+restricted	O
+to	O
++	O
+/	O
+-	O
+2	O
+standard	O
+deviations	O
+from	O
+their	O
+mean	O
+value	O
+for	O
+structures	O
+within	O
+10	O
+kcal	O
+of	O
+the	O
+best	O
+structure	O
+.	O
+
+MCSA	O
+cycles	O
+were	O
+repeated	O
+as	O
+described	O
+above	O
+with	O
+additional	O
+optimization	O
+of	O
+chi	O
+values	O
+:	O
+rotamers	O
+at	O
+the	O
+protein	O
+-	O
+protein	O
+interface	O
+were	O
+optimized	O
+with	O
+Dead	O
+End	O
+Elimination	O
+[	O
+72	O
+]	O
+,	O
+and	O
+chi	O
+values	O
+were	O
+further	O
+optimized	O
+with	O
+Monte	O
+Carlo	O
+.	O
+
+All	O
+MCSA	O
+cycles	O
+converged	O
+upon	O
+structures	O
+that	O
+were	O
+within	O
+a	O
+root	O
+mean	O
+squared	O
+deviation	O
+(	O
+RMSD	O
+)	O
+of	O
+1	O
+.	O
+5	O
+A	O
+with	O
+the	O
+best	O
+structure	O
+,	O
+and	O
+structures	O
+that	O
+scored	O
+within	O
+5	O
+kcal	O
+of	O
+the	O
+best	O
+score	O
+had	O
+an	O
+RMSD	O
+of	O
+less	O
+than	O
+0	O
+.	O
+5	O
+A	O
+with	O
+the	O
+best	O
+structure	O
+.	O
+
+List	O
+of	O
+abbreviations	O
+
+2	O
+-	O
+BP	O
+,	O
+2	O
+-	O
+bromopalmitate	O
+;	O
+CuP	O
+,	O
+Cu2	O
++	O
+-	O
+phenanthroline	O
+;	O
+DTME	O
+,	O
+dithio	O
+-	O
+bis	O
+-	O
+maleimidoethane	O
+;	O
+LEL	O
+,	O
+large	O
+extracellular	O
+loop	O
+;	O
+NEM	O
+,	O
+N	O
+-	O
+ethylmaleimide	O
+;	O
+TM	O
+,	O
+transmembrane	O
+(	O
+domain	O
+)	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+OVK	O
+carried	O
+out	O
+sequence	O
+comparisons	O
+,	O
+mutational	O
+analysis	O
+and	O
+cross	O
+-	O
+linking	O
+experiments	O
+,	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+DGM	O
+built	O
+the	O
+TM1	O
+-	O
+TM2	O
+interaction	O
+model	O
+and	O
+contributed	O
+to	O
+the	O
+manuscript	O
+.	O
+
+WFD	O
+supervised	O
+DGM	O
+'	O
+s	O
+work	O
+.	O
+
+MEH	O
+coordinated	O
+the	O
+whole	O
+study	O
+and	O
+prepared	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Epigenetic	O
+inactivation	O
+and	O
+aberrant	O
+transcription	O
+of	O
+CSMD1	O
+in	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+
+Abstract	O
+
+Background	O
+
+The	O
+p23	O
+.	O
+2	O
+region	O
+of	O
+human	B
+chromosome	O
+8	O
+is	O
+frequently	O
+deleted	O
+in	O
+several	O
+types	O
+of	O
+epithelial	O
+cancer	O
+and	O
+those	O
+deletions	O
+appear	O
+to	O
+be	O
+associated	O
+with	O
+poor	O
+prognosis	O
+.	O
+
+Cub	O
+and	O
+Sushi	O
+Multiple	O
+Domains	O
+1	O
+(	O
+CSMD1	O
+)	O
+was	O
+positionally	O
+cloned	O
+as	O
+a	O
+candidate	O
+for	O
+the	O
+8p23	O
+suppressor	O
+but	O
+point	O
+mutations	O
+in	O
+this	O
+gene	O
+are	O
+rare	O
+relative	O
+to	O
+the	O
+frequency	O
+of	O
+allelic	O
+loss	O
+.	O
+
+In	O
+an	O
+effort	O
+to	O
+identify	O
+alternative	O
+mechanisms	O
+of	O
+inactivation	O
+,	O
+we	O
+have	O
+characterized	O
+CSMD1	O
+expression	O
+and	O
+epigenetic	O
+modifications	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+.	O
+
+Results	O
+
+Only	O
+one	O
+of	O
+the	O
+20	O
+cell	O
+lines	O
+examined	O
+appears	O
+to	O
+express	O
+a	O
+structurally	O
+normal	O
+CSMD1	O
+transcript	O
+.	O
+
+The	O
+rest	O
+express	O
+transcripts	O
+which	O
+either	O
+lack	O
+internal	O
+exons	O
+,	O
+terminate	O
+abnormally	O
+or	O
+initiate	O
+at	O
+cryptic	O
+promoters	O
+.	O
+
+None	O
+of	O
+these	O
+truncated	O
+transcripts	O
+is	O
+predicted	O
+to	O
+encode	O
+a	O
+functional	O
+CSMD1	O
+protein	O
+.	O
+
+Cell	O
+lines	O
+that	O
+express	O
+little	O
+or	O
+no	O
+CSMD1	O
+RNA	O
+exhibit	O
+DNA	O
+methylation	O
+of	O
+a	O
+specific	O
+region	O
+of	O
+the	O
+CpG	O
+island	O
+surrounding	O
+CSMD1	O
+'	O
+s	O
+first	O
+exon	O
+.	O
+
+Conclusion	O
+
+Correlating	O
+methylation	O
+patterns	O
+and	O
+expression	O
+suggests	O
+that	O
+it	O
+is	O
+modification	O
+of	O
+the	O
+genomic	O
+DNA	O
+preceding	O
+the	O
+first	O
+exon	O
+that	O
+is	O
+associated	O
+with	O
+gene	O
+silencing	O
+and	O
+that	O
+methylation	O
+of	O
+CpG	O
+dinucleotides	O
+further	O
+3	O
+'	O
+does	O
+not	O
+contribute	O
+to	O
+inactivation	O
+of	O
+the	O
+gene	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+cell	O
+line	O
+data	O
+suggest	O
+that	O
+epigenetic	O
+silencing	O
+and	O
+aberrant	O
+splicing	O
+rather	O
+than	O
+point	O
+mutations	O
+may	O
+be	O
+contributing	O
+to	O
+the	O
+reduction	O
+in	O
+CSMD1	O
+expression	O
+in	O
+squamous	O
+cancers	O
+.	O
+
+These	O
+mechanisms	O
+can	O
+now	O
+serve	O
+as	O
+a	O
+focus	O
+for	O
+further	O
+analysis	O
+of	O
+primary	O
+squamous	O
+cancers	O
+.	O
+
+Background	O
+
+CUB	O
+and	O
+Sushi	O
+Multiple	O
+Domains	O
+1	O
+(	O
+CSMD1	O
+)	O
+was	O
+cloned	O
+as	O
+a	O
+candidate	O
+tumor	O
+suppressor	O
+or	O
+progression	O
+gene	O
+from	O
+a	O
+region	O
+of	O
+human	B
+chromosome	O
+8	O
+deleted	O
+in	O
+tumors	O
+of	O
+the	O
+upper	O
+aerodigestive	O
+tract	O
+,	O
+prostate	O
+,	O
+ovary	O
+and	O
+bladder	O
+[	O
+1	O
+-	O
+7	O
+]	O
+.	O
+
+Deletion	O
+of	O
+8p23	O
+.	O
+2	O
+or	O
+reduced	O
+expression	O
+of	O
+CSMD1	O
+has	O
+been	O
+associated	O
+with	O
+poor	O
+prognosis	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinomas	O
+and	O
+in	O
+prostate	O
+cancers	O
+[	O
+2	O
+,	O
+5	O
+,	O
+8	O
+]	O
+.	O
+
+CSMD1	O
+,	O
+consisting	O
+of	O
+70	O
+exons	O
+spread	O
+over	O
+two	O
+megabases	O
+of	O
+8p23	O
+.	O
+2	O
+,	O
+encodes	O
+a	O
+rare	O
+11	O
+.	O
+5	O
+kb	O
+transcript	O
+most	O
+abundantly	O
+expressed	O
+in	O
+the	O
+brain	O
+[	O
+1	O
+]	O
+.	O
+
+It	O
+is	O
+the	O
+founding	O
+member	O
+of	O
+a	O
+novel	O
+,	O
+evolutionarily	O
+highly	O
+conserved	O
+gene	O
+family	O
+whose	O
+proteins	O
+contain	O
+multiple	O
+domains	O
+thought	O
+to	O
+be	O
+sites	O
+of	O
+protein	O
+-	O
+protein	O
+or	O
+protein	O
+-	O
+ligand	O
+interactions	O
+and	O
+whose	O
+structure	O
+suggests	O
+that	O
+they	O
+may	O
+be	O
+transmembrane	O
+receptors	O
+or	O
+adhesion	O
+proteins	O
+[	O
+9	O
+,	O
+10	O
+]	O
+.	O
+
+Tumor	O
+suppressor	O
+genes	O
+are	O
+expected	O
+to	O
+be	O
+inactivated	O
+in	O
+cancers	O
+either	O
+genetically	O
+by	O
+mutations	O
+or	O
+epigenetically	O
+by	O
+modification	O
+of	O
+their	O
+promoters	O
+.	O
+
+While	O
+CSMD1	O
+transcripts	O
+are	O
+detectable	O
+in	O
+upper	O
+aerodigestive	O
+tract	O
+epithelium	O
+,	O
+preliminary	O
+analysis	O
+of	O
+several	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+suggested	O
+that	O
+CSMD1	O
+expression	O
+was	O
+lost	O
+in	O
+these	O
+lines	O
+[	O
+1	O
+]	O
+.	O
+
+Although	O
+the	O
+region	O
+containing	O
+CSMD1	O
+is	O
+frequently	O
+deleted	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinomas	O
+and	O
+prostatic	O
+adenocarcinomas	O
+[	O
+3	O
+,	O
+11	O
+-	O
+15	O
+]	O
+,	O
+point	O
+mutations	O
+in	O
+the	O
+gene	O
+are	O
+relatively	O
+rare	O
+in	O
+primary	O
+squamous	O
+cancers	O
+[	O
+16	O
+]	O
+and	O
+in	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+(	O
+Schmidt	O
+,	O
+Richter	O
+and	O
+Scholnick	O
+,	O
+unpublished	O
+)	O
+.	O
+
+Nonsense	O
+or	O
+splice	O
+junction	O
+mutations	O
+in	O
+CSMD1	O
+have	O
+not	O
+been	O
+reported	O
+and	O
+not	O
+enough	O
+is	O
+known	O
+about	O
+the	O
+function	O
+of	O
+the	O
+protein	O
+to	O
+accurately	O
+assess	O
+the	O
+effect	O
+of	O
+the	O
+few	O
+missense	O
+mutations	O
+that	O
+have	O
+been	O
+detected	O
+.	O
+
+Thus	O
+,	O
+if	O
+CSMD1	O
+is	O
+inactivated	O
+in	O
+tumors	O
+,	O
+alternative	O
+mechanisms	O
+for	O
+gene	O
+silencing	O
+must	O
+be	O
+operating	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+demonstrate	O
+that	O
+while	O
+most	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+do	O
+not	O
+express	O
+full	O
+length	O
+CSMD1	O
+transcripts	O
+,	O
+nearly	O
+all	O
+produce	O
+abnormal	O
+transcripts	O
+unlikely	O
+to	O
+encode	O
+functional	O
+CSMD1	O
+proteins	O
+.	O
+
+Methylation	O
+of	O
+the	O
+DNA	O
+preceding	O
+CSMD1	O
+'	O
+s	O
+first	O
+exon	O
+is	O
+correlated	O
+with	O
+reduction	O
+in	O
+the	O
+level	O
+of	O
+expression	O
+and	O
+cell	O
+lines	O
+expressing	O
+at	O
+low	O
+levels	O
+do	O
+not	O
+appear	O
+to	O
+elongate	O
+the	O
+full	O
+11	O
+.	O
+5	O
+kb	O
+transcript	O
+.	O
+
+Other	O
+anomalies	O
+of	O
+expression	O
+include	O
+incorrect	O
+splicing	O
+and	O
+the	O
+use	O
+of	O
+cryptic	O
+promoters	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+activation	O
+of	O
+these	O
+promoters	O
+may	O
+result	O
+from	O
+the	O
+global	O
+demethylation	O
+of	O
+the	O
+genome	O
+associated	O
+with	O
+tumorigenesis	O
+(	O
+reviewed	O
+by	O
+Ehrlich	O
+[	O
+17	O
+]	O
+)	O
+.	O
+
+Taken	O
+together	O
+these	O
+data	O
+demonstrate	O
+that	O
+mechanisms	O
+other	O
+than	O
+point	O
+mutation	O
+are	O
+responsible	O
+for	O
+the	O
+aberrant	O
+CSMD1	O
+expression	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+,	O
+and	O
+these	O
+data	O
+suggest	O
+potential	O
+targets	O
+for	O
+further	O
+investigation	O
+in	O
+primary	O
+tumors	O
+.	O
+
+Results	O
+
+CSMD1	O
+promoter	O
+methylation	O
+in	O
+HNSCC	O
+cell	O
+lines	O
+is	O
+correlated	O
+with	O
+expression	O
+levels	O
+
+Preliminary	O
+evidence	O
+suggested	O
+that	O
+CSMD1	O
+expression	O
+is	O
+lost	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinomas	O
+[	O
+1	O
+]	O
+but	O
+that	O
+point	O
+mutations	O
+were	O
+rare	O
+[	O
+[	O
+16	O
+]	O
+,	O
+and	O
+Schmidt	O
+,	O
+Richter	O
+and	O
+Scholnick	O
+,	O
+unpublished	O
+]	O
+.	O
+
+To	O
+date	O
+,	O
+only	O
+two	O
+of	O
+the	O
+20	O
+cell	O
+lines	O
+we	O
+have	O
+tested	O
+for	O
+CSMD1	O
+expression	O
+,	O
+UPCI	O
+:	O
+SCC066	O
+and	O
+PCI	O
+-	O
+13	O
+,	O
+express	O
+large	O
+transcripts	O
+initiated	O
+at	O
+the	O
+normal	O
+CSMD1	O
+promoter	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+a	O
+mechanism	O
+(	O
+s	O
+)	O
+other	O
+than	O
+point	O
+mutation	O
+must	O
+be	O
+responsible	O
+for	O
+the	O
+loss	O
+of	O
+expression	O
+.	O
+
+CSMD1	O
+'	O
+s	O
+first	O
+exon	O
+is	O
+embedded	O
+in	O
+a	O
+3	O
+.	O
+7	O
+kb	O
+CpG	O
+island	O
+(	O
+data	O
+from	O
+the	O
+UCSC	O
+genome	O
+browser	O
+[	O
+18	O
+]	O
+)	O
+suggesting	O
+that	O
+promoter	O
+methylation	O
+might	O
+epigenetically	O
+silence	O
+the	O
+gene	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+we	O
+surveyed	O
+32	O
+head	O
+and	O
+neck	O
+cancer	O
+cell	O
+lines	O
+for	O
+CSMD1	O
+promoter	O
+methylation	O
+using	O
+the	O
+Combined	O
+Bisulfite	O
+Restriction	O
+Analysis	O
+(	O
+COBRA	O
+)	O
+technique	O
+described	O
+by	O
+Xiong	O
+and	O
+Laird	O
+(	O
+Methods	O
+)	O
+[	O
+19	O
+]	O
+.	O
+
+COBRA	O
+analysis	O
+of	O
+the	O
+three	O
+amplicons	O
+diagrammed	O
+in	O
+Figure	O
+1	O
+suggested	O
+that	O
+28	O
+of	O
+the	O
+cell	O
+lines	O
+(	O
+87	O
+%	O
+)	O
+had	O
+more	O
+promoter	O
+methylation	O
+than	O
+did	O
+normal	O
+upper	O
+aerodigestive	O
+epithelium	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+We	O
+selected	O
+nine	O
+of	O
+these	O
+cell	O
+lines	O
+for	O
+high	O
+resolution	O
+analysis	O
+of	O
+promoter	O
+methylation	O
+by	O
+sequencing	O
+of	O
+clones	O
+from	O
+bisulfite	O
+converted	O
+genomic	O
+DNA	O
+.	O
+
+This	O
+approach	O
+has	O
+the	O
+distinct	O
+advantage	O
+of	O
+allowing	O
+determination	O
+of	O
+the	O
+state	O
+of	O
+all	O
+the	O
+CpG	O
+dinucleotides	O
+within	O
+an	O
+amplicon	O
+on	O
+an	O
+allele	O
+by	O
+allele	O
+basis	O
+.	O
+
+Amplicons	O
+1	O
+and	O
+2	O
+have	O
+19	O
+and	O
+20	O
+CpG	O
+dinucleotides	O
+,	O
+respectively	O
+.	O
+
+Amplicon	O
+3	O
+could	O
+not	O
+be	O
+examined	O
+by	O
+this	O
+technique	O
+because	O
+it	O
+is	O
+unclonable	O
+after	O
+bisulfite	O
+conversion	O
+.	O
+
+The	O
+methylation	O
+data	O
+were	O
+correlated	O
+to	O
+CSMD1	O
+expression	O
+levels	O
+as	O
+measured	O
+by	O
+quantitative	O
+RT	O
+-	O
+PCR	O
+using	O
+an	O
+amplicon	O
+spanning	O
+exons	O
+1	O
+and	O
+2	O
+(	O
+Methods	O
+)	O
+.	O
+
+A	O
+pool	O
+of	O
+cDNA	O
+from	O
+five	O
+normal	O
+oropharyngeal	O
+epithelium	O
+specimens	O
+served	O
+as	O
+a	O
+basis	O
+for	O
+comparison	O
+to	O
+the	O
+cell	O
+lines	O
+.	O
+
+Our	O
+data	O
+from	O
+amplicon	O
+1	O
+demonstrate	O
+a	O
+clear	O
+relationship	O
+between	O
+methylation	O
+and	O
+the	O
+level	O
+of	O
+expression	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+The	O
+bisulfite	O
+sequencing	O
+data	O
+confirm	O
+that	O
+there	O
+is	O
+relatively	O
+little	O
+promoter	O
+methylation	O
+in	O
+normal	O
+tissue	O
+(	O
+clones	O
+1	O
+-	O
+20	O
+,	O
+Figure	O
+2A	O
+)	O
+.	O
+
+This	O
+is	O
+also	O
+the	O
+case	O
+in	O
+cell	O
+line	O
+UPCI	O
+:	O
+SCC066	O
+which	O
+expresses	O
+a	O
+large	O
+CSMD1	O
+transcript	O
+from	O
+the	O
+normal	O
+promoter	O
+at	O
+a	O
+level	O
+approximately	O
+33	O
+%	O
+of	O
+that	O
+of	O
+normal	O
+tissue	O
+(	O
+clones	O
+32	O
+-	O
+39	O
+,	O
+Figure	O
+2B	O
+)	O
+.	O
+
+PCI	O
+-	O
+13	O
+,	O
+our	O
+highest	O
+expressing	O
+line	O
+at	O
+125	O
+%	O
+of	O
+normal	O
+epithelium	O
+,	O
+displays	O
+two	O
+distinct	O
+patterns	O
+of	O
+promoter	O
+methylation	O
+with	O
+some	O
+clones	O
+heavily	O
+methylated	O
+(	O
+clones	O
+21	O
+-	O
+24	O
+,	O
+and	O
+30	O
+)	O
+and	O
+others	O
+with	O
+no	O
+methylation	O
+(	O
+clones	O
+25	O
+-	O
+39	O
+and	O
+31	O
+;	O
+Figure	O
+2B	O
+)	O
+.	O
+
+This	O
+pattern	O
+is	O
+consistent	O
+with	O
+either	O
+heterozygosity	O
+for	O
+methylation	O
+or	O
+the	O
+co	O
+-	O
+existence	O
+of	O
+2	O
+distinct	O
+populations	O
+within	O
+the	O
+cell	O
+line	O
+,	O
+one	O
+heavily	O
+methylated	O
+and	O
+one	O
+unmethylated	O
+.	O
+
+We	O
+cannot	O
+distinguish	O
+between	O
+these	O
+two	O
+possibilities	O
+using	O
+the	O
+currently	O
+available	O
+data	O
+.	O
+
+The	O
+remaining	O
+cell	O
+lines	O
+express	O
+CSMD1	O
+at	O
+a	O
+level	O
+half	O
+that	O
+of	O
+UPCI	O
+:	O
+SCC066	O
+or	O
+less	O
+(	O
+ranging	O
+from	O
+17	O
+%	O
+to	O
+1	O
+%	O
+of	O
+normal	O
+epithelium	O
+)	O
+and	O
+they	O
+exhibit	O
+considerably	O
+greater	O
+methylation	O
+of	O
+amplicon	O
+1	O
+(	O
+clones	O
+40	O
+-	O
+76	O
+,	O
+Figure	O
+2C	O
+)	O
+.	O
+
+Cell	O
+lines	O
+with	O
+more	O
+amplicon	O
+1	O
+methylation	O
+tend	O
+to	O
+express	O
+the	O
+gene	O
+at	O
+lower	O
+levels	O
+but	O
+the	O
+relationship	O
+is	O
+not	O
+strictly	O
+quantitative	O
+(	O
+Figure	O
+2C	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+our	O
+data	O
+revealed	O
+no	O
+relationship	O
+between	O
+expression	O
+level	O
+and	O
+methylation	O
+of	O
+amplicon	O
+2	O
+(	O
+located	O
+towards	O
+the	O
+3	O
+'	O
+end	O
+of	O
+exon	O
+1	O
+,	O
+Figure	O
+1	O
+)	O
+.	O
+
+For	O
+example	O
+,	O
+all	O
+of	O
+the	O
+10	O
+clones	O
+of	O
+amplicon	O
+2	O
+sequenced	O
+from	O
+PCI	O
+-	O
+13	O
+were	O
+methylated	O
+at	O
+19	O
+or	O
+20	O
+of	O
+their	O
+20	O
+CpG	O
+dinucleotides	O
+.	O
+
+UPCI	O
+:	O
+SCC066	O
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+has	O
+nearly	O
+no	O
+methylation	O
+in	O
+amplicon	O
+2	O
+with	O
+only	O
+a	O
+single	O
+methylated	O
+CpG	O
+dinucleotide	O
+detected	O
+in	O
+one	O
+clone	O
+out	O
+of	O
+the	O
+nine	O
+sequenced	O
+.	O
+
+Amplicon	O
+2	O
+ranges	O
+from	O
+completely	O
+unmethylated	O
+to	O
+heavily	O
+methylated	O
+in	O
+the	O
+seven	O
+remaining	O
+cell	O
+lines	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Low	O
+transcript	O
+levels	O
+are	O
+accompanied	O
+by	O
+a	O
+failure	O
+to	O
+elongate	O
+the	O
+full	O
+CSMD1	O
+transcript	O
+
+On	O
+the	O
+surface	O
+,	O
+the	O
+quantitative	O
+RT	O
+-	O
+PCR	O
+data	O
+presented	O
+in	O
+Figure	O
+2	O
+suggest	O
+that	O
+the	O
+cell	O
+lines	O
+we	O
+consider	O
+low	O
+expressing	O
+might	O
+still	O
+have	O
+up	O
+to	O
+17	O
+%	O
+of	O
+the	O
+normal	O
+level	O
+of	O
+CSMD1	O
+transcript	O
+.	O
+
+A	O
+survey	O
+of	O
+20	O
+cell	O
+lines	O
+using	O
+a	O
+battery	O
+of	O
+RT	O
+-	O
+PCR	O
+primer	O
+pairs	O
+located	O
+throughout	O
+the	O
+11	O
+.	O
+5	O
+kb	O
+transcript	O
+reveals	O
+that	O
+this	O
+is	O
+not	O
+the	O
+case	O
+.	O
+
+These	O
+lines	O
+included	O
+OKF6	O
+-	O
+TERT1	O
+,	O
+a	O
+TERT	O
+immortalized	O
+,	O
+p16	O
+deficient	O
+but	O
+untransformed	O
+oral	O
+keratinocyte	O
+cell	O
+line	O
+[	O
+20	O
+]	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+the	O
+low	O
+expressing	O
+cell	O
+lines	O
+shown	O
+in	O
+Figure	O
+2C	O
+express	O
+considerably	O
+more	O
+of	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+11	O
+.	O
+5	O
+kb	O
+transcript	O
+than	O
+they	O
+do	O
+exons	O
+further	O
+3	O
+'	O
+,	O
+a	O
+phenomenon	O
+well	O
+illustrated	O
+by	O
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+line	O
+PCI	O
+-	O
+100	O
+.	O
+
+This	O
+line	O
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+the	O
+exon	O
+1	O
+/	O
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+approximately	O
+15	O
+%	O
+of	O
+the	O
+level	O
+of	O
+normal	O
+epithelium	O
+.	O
+
+In	O
+contrast	O
+,	O
+we	O
+had	O
+previously	O
+reported	O
+that	O
+CSMD1	O
+transcripts	O
+were	O
+not	O
+detectable	O
+in	O
+this	O
+line	O
+by	O
+combined	O
+RT	O
+-	O
+PCR	O
+and	O
+Southern	O
+blotting	O
+using	O
+three	O
+sets	O
+of	O
+intron	O
+spanning	O
+primers	O
+[	O
+1	O
+]	O
+.	O
+
+The	O
+most	O
+5	O
+'	O
+of	O
+those	O
+amplicons	O
+spans	O
+exons	O
+9	O
+through	O
+26	O
+.	O
+
+Analysis	O
+with	O
+additional	O
+primer	O
+pairs	O
+resolves	O
+this	O
+apparent	O
+paradox	O
+by	O
+demonstrating	O
+that	O
+the	O
+amount	O
+of	O
+transcript	O
+declines	O
+sharply	O
+and	O
+reproducibly	O
+as	O
+one	O
+examines	O
+progressively	O
+more	O
+3	O
+'	O
+exons	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+The	O
+same	O
+effect	O
+is	O
+seen	O
+using	O
+either	O
+oligo	O
+-	O
+dT	O
+or	O
+random	O
+hexamer	O
+primed	O
+cDNA	O
+.	O
+
+No	O
+transcript	O
+of	O
+this	O
+structure	O
+has	O
+been	O
+detected	O
+in	O
+normal	O
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+nor	O
+have	O
+we	O
+detected	O
+any	O
+sequence	O
+alterations	O
+in	O
+PCI	O
+-	O
+100	O
+that	O
+would	O
+explain	O
+why	O
+the	O
+full	O
+transcript	O
+is	O
+not	O
+expressed	O
+.	O
+
+It	O
+is	O
+not	O
+clear	O
+whether	O
+PCI	O
+-	O
+100	O
+produces	O
+a	O
+small	O
+number	O
+of	O
+discrete	O
+size	O
+classes	O
+of	O
+transcript	O
+,	O
+if	O
+individual	O
+transcripts	O
+terminate	O
+at	O
+random	O
+points	O
+within	O
+the	O
+very	O
+large	O
+introns	O
+in	O
+this	O
+part	O
+of	O
+the	O
+gene	O
+(	O
+the	O
+first	O
+10	O
+introns	O
+average	O
+~	O
+150	O
+kb	O
+in	O
+length	O
+)	O
+,	O
+or	O
+if	O
+the	O
+short	O
+transcripts	O
+result	O
+from	O
+the	O
+elevated	O
+activity	O
+of	O
+a	O
+previously	O
+undetected	O
+posttranscriptional	O
+control	O
+mechanism	O
+.	O
+
+Inactivation	O
+of	O
+CSMD1	O
+by	O
+aberrant	O
+splicing	O
+
+Two	O
+cell	O
+lines	O
+,	O
+UPCI	O
+:	O
+SCC066	O
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+PCI	O
+-	O
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+,	O
+express	O
+large	O
+CSMD1	O
+transcripts	O
+initiated	O
+at	O
+the	O
+normal	O
+promoter	O
+.	O
+
+Subsequent	O
+finer	O
+scale	O
+analysis	O
+demonstrates	O
+that	O
+PCI	O
+-	O
+13	O
+'	O
+s	O
+transcript	O
+lacks	O
+exons	O
+4	O
+and	O
+5	O
+,	O
+resulting	O
+in	O
+a	O
+frameshift	O
+-	O
+induced	O
+nonsense	O
+codon	O
+in	O
+exon	O
+6	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+Sequencing	O
+of	O
+the	O
+PCI	O
+-	O
+13	O
+RT	O
+-	O
+PCR	O
+product	O
+demonstrates	O
+the	O
+direct	O
+juxtaposition	O
+of	O
+wildtype	O
+exons	O
+3	O
+and	O
+6	O
+and	O
+that	O
+the	O
+transcript	O
+contains	O
+no	O
+novel	O
+sequences	O
+or	O
+splices	O
+that	O
+would	O
+prevent	O
+the	O
+frameshift	O
+.	O
+
+UPCI	O
+:	O
+SCC066	O
+produces	O
+two	O
+transcripts	O
+,	O
+a	O
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+that	O
+includes	O
+exons	O
+4	O
+and	O
+5	O
+and	O
+another	O
+that	O
+lacks	O
+them	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+RT	O
+-	O
+PCR	O
+of	O
+human	B
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+very	O
+low	O
+levels	O
+of	O
+an	O
+RT	O
+-	O
+PCR	O
+product	O
+corresponding	O
+in	O
+size	O
+to	O
+that	O
+expected	O
+from	O
+the	O
+internally	O
+deleted	O
+transcript	O
+.	O
+
+This	O
+band	O
+is	O
+not	O
+readily	O
+visible	O
+at	O
+the	O
+exposure	O
+used	O
+for	O
+Figure	O
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+.	O
+
+We	O
+have	O
+not	O
+detected	O
+a	O
+similar	O
+sized	O
+PCR	O
+product	O
+in	O
+RNA	O
+from	O
+oropharyngeal	O
+epithelium	O
+but	O
+this	O
+may	O
+reflect	O
+the	O
+fact	O
+that	O
+CSMD1	O
+transcripts	O
+are	O
+~	O
+10x	O
+less	O
+abundant	O
+in	O
+oropharyngeal	O
+epithelium	O
+than	O
+they	O
+are	O
+in	O
+fetal	O
+brain	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+transcripts	O
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+4	O
+and	O
+5	O
+appear	O
+to	O
+result	O
+from	O
+aberrant	O
+splicing	O
+rather	O
+than	O
+somatic	O
+deletion	O
+of	O
+these	O
+two	O
+exons	O
+or	O
+mutations	O
+of	O
+their	O
+splicing	O
+consensus	O
+sequences	O
+.	O
+
+Exons	O
+4	O
+and	O
+5	O
+can	O
+be	O
+amplified	O
+from	O
+PCI	O
+-	O
+13	O
+genomic	O
+DNA	O
+and	O
+sequencing	O
+of	O
+those	O
+PCR	O
+products	O
+demonstrates	O
+that	O
+both	O
+their	O
+coding	O
+sequences	O
+and	O
+consensus	O
+splice	O
+sites	O
+are	O
+wildtype	O
+.	O
+
+Activation	O
+of	O
+cryptic	O
+promoters	O
+in	O
+cancer	O
+cell	O
+lines	O
+
+The	O
+RT	O
+-	O
+PCR	O
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+revealed	O
+a	O
+second	O
+transcriptional	O
+anomaly	O
+exhibited	O
+by	O
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+cell	O
+lines	O
+:	O
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+,	O
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+,	O
+PCI	O
+-	O
+1	O
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+-	O
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+.	O
+
+Like	O
+PCI	O
+-	O
+100	O
+,	O
+these	O
+lines	O
+express	O
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+levels	O
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+very	O
+5	O
+'	O
+end	O
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+the	O
+transcript	O
+and	O
+even	O
+lower	O
+levels	O
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+more	O
+3	O
+'	O
+exons	O
+within	O
+the	O
+first	O
+half	O
+of	O
+the	O
+transcript	O
+.	O
+
+However	O
+,	O
+these	O
+lines	O
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+in	O
+expressing	O
+higher	O
+levels	O
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+the	O
+3	O
+'	O
+half	O
+of	O
+the	O
+transcript	O
+,	O
+suggesting	O
+that	O
+alternative	O
+promoters	O
+in	O
+the	O
+middle	O
+of	O
+the	O
+gene	O
+may	O
+be	O
+used	O
+.	O
+
+SCC9	O
+was	O
+chosen	O
+for	O
+further	O
+study	O
+because	O
+it	O
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+the	O
+3	O
+'	O
+half	O
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+the	O
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+level	O
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+higher	O
+than	O
+normal	O
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+.	O
+
+Northern	O
+blotting	O
+detects	O
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+abundant	O
+6	O
+.	O
+4	O
+kb	O
+truncated	O
+transcript	O
+as	O
+well	O
+as	O
+smaller	O
+amounts	O
+of	O
+an	O
+8	O
+.	O
+7	O
+kb	O
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+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+The	O
+other	O
+three	O
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+lines	O
+express	O
+their	O
+truncated	O
+CSMD1	O
+transcripts	O
+at	O
+lower	O
+levels	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Sequence	O
+analysis	O
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+cDNA	O
+clones	O
+from	O
+SCC9	O
+demonstrates	O
+that	O
+many	O
+transcripts	O
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+improperly	O
+spliced	O
+,	O
+resulting	O
+in	O
+retention	O
+of	O
+intronic	O
+sequences	O
+and	O
+/	O
+or	O
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+of	O
+exonic	O
+sequences	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+In	O
+particular	O
+,	O
+retention	O
+of	O
+sequences	O
+from	O
+intron	O
+40	O
+is	O
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+.	O
+
+The	O
+high	O
+frequency	O
+of	O
+faulty	O
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+may	O
+explain	O
+the	O
+broadness	O
+of	O
+the	O
+6	O
+.	O
+4	O
+kb	O
+CSMD1	O
+band	O
+in	O
+Figure	O
+5A	O
+and	O
+suggests	O
+that	O
+the	O
+8	O
+.	O
+7	O
+kb	O
+transcript	O
+may	O
+also	O
+be	O
+incompletely	O
+or	O
+improperly	O
+spliced	O
+.	O
+
+5	O
+'	O
+RACE	O
+[	O
+21	O
+]	O
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+that	O
+the	O
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+message	O
+is	O
+initiated	O
+just	O
+upstream	O
+of	O
+an	O
+Alu	O
+element	O
+in	O
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+36	O
+(	O
+Figure	O
+5B	O
+)	O
+.	O
+
+Only	O
+the	O
+5	O
+'	O
+-	O
+most	O
+120	O
+base	O
+pairs	O
+of	O
+the	O
+Alu	O
+element	O
+are	O
+present	O
+in	O
+the	O
+genome	O
+.	O
+
+RT	O
+-	O
+PCR	O
+using	O
+a	O
+forward	O
+primer	O
+specific	O
+for	O
+the	O
+novel	O
+sequences	O
+of	O
+the	O
+SCC9	O
+transcript	O
+(	O
+prm1904	O
+,	O
+cgtttagttcgacacacttc	O
+)	O
+demonstrates	O
+that	O
+cell	O
+lines	O
+041	O
+,	O
+PCI	O
+-	O
+1	O
+and	O
+PCI	O
+-	O
+2	O
+do	O
+not	O
+initiate	O
+their	O
+CSMD1	O
+transcripts	O
+at	O
+the	O
+same	O
+point	O
+,	O
+suggesting	O
+that	O
+other	O
+cryptic	O
+promoters	O
+are	O
+active	O
+in	O
+these	O
+lines	O
+.	O
+
+The	O
+sequence	O
+of	O
+this	O
+novel	O
+exon	O
+has	O
+been	O
+entered	O
+in	O
+Genbank	O
+as	O
+accession	O
+number	O
+DQ093422	O
+.	O
+
+DNA	O
+methyltransferase	O
+inhibitors	O
+activate	O
+the	O
+same	O
+cryptic	O
+promoter	O
+used	O
+in	O
+cell	O
+line	O
+SCC9	O
+
+Expression	O
+from	O
+epigenetically	O
+silenced	O
+promoters	O
+can	O
+sometimes	O
+be	O
+restored	O
+by	O
+treatment	O
+with	O
+inhibitors	O
+of	O
+DNA	O
+methyltransferase	O
+or	O
+histone	O
+deacetylase	O
+activity	O
+(	O
+[	O
+22	O
+]	O
+)	O
+.	O
+
+We	O
+selected	O
+two	O
+low	O
+expressing	O
+cell	O
+lines	O
+with	O
+promoter	O
+methylation	O
+,	O
+UPCI	O
+:	O
+SCC104	O
+and	O
+094	O
+,	O
+for	O
+treatment	O
+with	O
+various	O
+concentrations	O
+of	O
+5	O
+-	O
+azacytidine	O
+or	O
+5	O
+-	O
+aza	O
+-	O
+2	O
+'	O
+-	O
+deoxycytidine	O
+(	O
+5	O
+-	O
+aza	O
+-	O
+dC	O
+)	O
+as	O
+well	O
+as	O
+combinations	O
+of	O
+either	O
+of	O
+those	O
+drugs	O
+with	O
+the	O
+histone	O
+deacetylase	O
+inhibitor	O
+trichostatin	O
+A	O
+.	O
+
+These	O
+treatments	O
+did	O
+not	O
+reactivate	O
+the	O
+silenced	O
+CSMD1	O
+promoter	O
+.	O
+
+COBRA	O
+analysis	O
+of	O
+genomic	O
+DNA	O
+from	O
+the	O
+treated	O
+cells	O
+suggested	O
+that	O
+the	O
+drugs	O
+did	O
+not	O
+robustly	O
+affect	O
+methylation	O
+of	O
+the	O
+CSMD1	O
+promoter	O
+even	O
+at	O
+levels	O
+high	O
+enough	O
+to	O
+be	O
+toxic	O
+to	O
+the	O
+cells	O
+.	O
+
+These	O
+experiments	O
+did	O
+however	O
+shed	O
+light	O
+on	O
+the	O
+cryptic	O
+promoter	O
+used	O
+in	O
+SCC9	O
+cells	O
+and	O
+on	O
+the	O
+interpretation	O
+of	O
+experiments	O
+using	O
+methyltransferase	O
+inhibitors	O
+.	O
+
+Treatment	O
+of	O
+cell	O
+line	O
+094	O
+with	O
+relatively	O
+high	O
+doses	O
+of	O
+5aza	O
+-	O
+dC	O
+results	O
+in	O
+the	O
+expression	O
+of	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+CSMD1	O
+transcript	O
+.	O
+
+This	O
+transcript	O
+was	O
+not	O
+detected	O
+in	O
+control	O
+094	O
+cells	O
+undergoing	O
+mock	O
+drug	O
+treatment	O
+(	O
+Figure	O
+6	O
+)	O
+nor	O
+was	O
+it	O
+detected	O
+in	O
+094	O
+cells	O
+growing	O
+under	O
+normal	O
+culture	O
+conditions	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+RT	O
+-	O
+PCR	O
+of	O
+cDNA	O
+from	O
+drug	O
+-	O
+treated	O
+094	O
+cells	O
+using	O
+the	O
+primer	O
+developed	O
+from	O
+the	O
+novel	O
+5	O
+'	O
+exon	O
+of	O
+SCC9	O
+'	O
+s	O
+truncated	O
+transcript	O
+(	O
+prm1904	O
+,	O
+see	O
+above	O
+)	O
+yielded	O
+a	O
+product	O
+identical	O
+in	O
+size	O
+to	O
+that	O
+amplified	O
+from	O
+SCC9	O
+cDNA	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+The	O
+identity	O
+of	O
+the	O
+product	O
+was	O
+confirmed	O
+by	O
+DNA	O
+sequencing	O
+which	O
+also	O
+revealed	O
+that	O
+the	O
+drug	O
+-	O
+induced	O
+094	O
+transcript	O
+was	O
+more	O
+faithfully	O
+spliced	O
+than	O
+the	O
+transcript	O
+expressed	O
+in	O
+SCC9	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Discussion	O
+
+Our	O
+data	O
+clearly	O
+demonstrate	O
+that	O
+expression	O
+of	O
+normal	O
+CSMD1	O
+transcripts	O
+is	O
+rare	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+.	O
+
+Of	O
+the	O
+HNSCC	O
+cell	O
+lines	O
+examined	O
+,	O
+only	O
+UPCI	O
+:	O
+SCC066	O
+appears	O
+to	O
+express	O
+a	O
+normal	O
+transcript	O
+from	O
+the	O
+expected	O
+promoter	O
+.	O
+
+Even	O
+that	O
+cell	O
+line	O
+produces	O
+a	O
+second	O
+species	O
+of	O
+aberrantly	O
+spliced	O
+transcript	O
+lacking	O
+internal	O
+exons	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+epigenetic	O
+modification	O
+of	O
+the	O
+DNA	O
+5	O
+'	O
+of	O
+the	O
+transcription	O
+start	O
+site	O
+may	O
+contribute	O
+to	O
+the	O
+down	O
+-	O
+regulation	O
+of	O
+CSMD1	O
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+low	O
+level	O
+of	O
+expression	O
+appears	O
+to	O
+be	O
+associated	O
+with	O
+production	O
+of	O
+prematurely	O
+terminated	O
+transcripts	O
+.	O
+
+This	O
+degree	O
+of	O
+complexity	O
+might	O
+be	O
+expected	O
+from	O
+a	O
+2	O
+megabase	O
+,	O
+70	O
+exon	O
+gene	O
+.	O
+
+Methylation	O
+of	O
+a	O
+specific	O
+region	O
+of	O
+the	O
+CpG	O
+island	O
+,	O
+-	O
+395	O
+to	O
+-	O
+112	O
+bp	O
+relative	O
+to	O
+the	O
+transcriptional	O
+start	O
+site	O
+(	O
+amplicon	O
+1	O
+)	O
+,	O
+appears	O
+to	O
+be	O
+correlated	O
+with	O
+the	O
+activity	O
+of	O
+the	O
+normal	O
+CSMD1	O
+promoter	O
+.	O
+
+In	O
+contrast	O
+,	O
+methylation	O
+of	O
+amplicon	O
+2	O
+,	O
+located	O
+within	O
+the	O
+first	O
+exon	O
+,	O
+shows	O
+no	O
+such	O
+relationship	O
+.	O
+
+Our	O
+data	O
+suggest	O
+that	O
+the	O
+relationship	O
+between	O
+the	O
+amount	O
+of	O
+methylation	O
+in	O
+amplicon	O
+1	O
+and	O
+the	O
+level	O
+of	O
+expression	O
+may	O
+not	O
+be	O
+strictly	O
+quantitative	O
+.	O
+
+Differences	O
+between	O
+cell	O
+lines	O
+with	O
+amplicon	O
+1	O
+methylation	O
+could	O
+arise	O
+through	O
+a	O
+number	O
+of	O
+mechanisms	O
+,	O
+for	O
+example	O
+,	O
+variations	O
+in	O
+the	O
+levels	O
+of	O
+transcription	O
+factors	O
+between	O
+cell	O
+lines	O
+.	O
+
+In	O
+cases	O
+where	O
+there	O
+is	O
+considerable	O
+heterogeneity	O
+in	O
+the	O
+methylation	O
+pattern	O
+within	O
+a	O
+cell	O
+line	O
+like	O
+PCI	O
+-	O
+100	O
+,	O
+alleles	O
+with	O
+less	O
+methylation	O
+may	O
+be	O
+expressed	O
+at	O
+higher	O
+levels	O
+than	O
+those	O
+more	O
+heavily	O
+methylated	O
+(	O
+compare	O
+clones	O
+51	O
+and	O
+52	O
+to	O
+clone	O
+58	O
+in	O
+Figure	O
+2C	O
+)	O
+.	O
+
+Alternatively	O
+,	O
+the	O
+presence	O
+of	O
+methylation	O
+in	O
+amplicon	O
+1	O
+could	O
+be	O
+a	O
+qualitative	O
+but	O
+not	O
+strictly	O
+quantitative	O
+indicator	O
+of	O
+methylation	O
+of	O
+a	O
+critical	O
+segment	O
+of	O
+the	O
+promoter	O
+not	O
+discovered	O
+in	O
+this	O
+study	O
+.	O
+
+The	O
+normal	O
+CSMD1	O
+promoter	O
+was	O
+not	O
+reactivated	O
+by	O
+drugs	O
+that	O
+inhibit	O
+DNA	O
+methyltransferases	O
+and	O
+histone	O
+deacetylases	O
+,	O
+nor	O
+did	O
+the	O
+drugs	O
+abolish	O
+CSMD1	O
+promoter	O
+methylation	O
+,	O
+even	O
+at	O
+toxic	O
+doses	O
+.	O
+
+Not	O
+all	O
+genes	O
+with	O
+promoter	O
+methylation	O
+respond	O
+to	O
+such	O
+treatments	O
+[	O
+23	O
+]	O
+.	O
+
+These	O
+drug	O
+treatments	O
+did	O
+,	O
+however	O
+,	O
+provide	O
+a	O
+potential	O
+explanation	O
+for	O
+the	O
+use	O
+of	O
+a	O
+normally	O
+cryptic	O
+promoter	O
+by	O
+cell	O
+line	O
+SCC9	O
+.	O
+
+The	O
+CSMD1	O
+transcript	O
+in	O
+this	O
+line	O
+is	O
+initiated	O
+near	O
+a	O
+partial	O
+Alu	O
+element	O
+.	O
+
+5	O
+-	O
+aza	O
+-	O
+dC	O
+treatment	O
+of	O
+cell	O
+line	O
+094	O
+activates	O
+the	O
+same	O
+cryptic	O
+promoter	O
+.	O
+
+This	O
+suggests	O
+that	O
+cryptic	O
+promoters	O
+may	O
+be	O
+naturally	O
+activated	O
+by	O
+general	O
+hypomethylation	O
+of	O
+the	O
+genome	O
+in	O
+cancer	O
+cells	O
+and	O
+the	O
+subsequent	O
+release	O
+of	O
+repetitive	O
+elements	O
+from	O
+epigenetic	O
+repression	O
+(	O
+reviewed	O
+by	O
+Ehrlich	O
+[	O
+17	O
+]	O
+)	O
+.	O
+
+The	O
+SCC9	O
+transcript	O
+does	O
+not	O
+appear	O
+to	O
+encode	O
+a	O
+functional	O
+protein	O
+but	O
+,	O
+with	O
+a	O
+very	O
+large	O
+gene	O
+like	O
+CSMD1	O
+,	O
+there	O
+is	O
+a	O
+potential	O
+for	O
+some	O
+abnormally	O
+initiated	O
+transcripts	O
+to	O
+encode	O
+truncated	O
+proteins	O
+with	O
+dominant	O
+negative	O
+properties	O
+.	O
+
+The	O
+second	O
+ramification	O
+of	O
+this	O
+finding	O
+is	O
+for	O
+the	O
+interpretation	O
+of	O
+data	O
+obtained	O
+by	O
+treating	O
+cells	O
+with	O
+methyltransferase	O
+inhibitors	O
+.	O
+
+Detection	O
+of	O
+CSMD1	O
+transcripts	O
+solely	O
+with	O
+primers	O
+mapping	O
+to	O
+the	O
+3	O
+'	O
+end	O
+of	O
+the	O
+gene	O
+could	O
+have	O
+been	O
+erroneously	O
+interpreted	O
+as	O
+representing	O
+reactivation	O
+of	O
+the	O
+normal	O
+promoter	O
+.	O
+
+It	O
+seems	O
+imperative	O
+that	O
+such	O
+experiments	O
+demonstrate	O
+that	O
+transcripts	O
+detected	O
+after	O
+drug	O
+treatment	O
+are	O
+actually	O
+initiated	O
+at	O
+the	O
+normal	O
+promoter	O
+.	O
+
+Aberrant	O
+splicing	O
+also	O
+appears	O
+to	O
+play	O
+a	O
+role	O
+in	O
+the	O
+production	O
+of	O
+defective	O
+CSMD1	O
+transcripts	O
+.	O
+
+Loss	O
+of	O
+splicing	O
+fidelity	O
+has	O
+been	O
+proposed	O
+as	O
+a	O
+characteristic	O
+of	O
+cancer	O
+cells	O
+[	O
+24	O
+,	O
+25	O
+]	O
+and	O
+this	O
+would	O
+be	O
+consistent	O
+with	O
+the	O
+variety	O
+of	O
+misspliced	O
+transcripts	O
+we	O
+detected	O
+from	O
+SCC9	O
+.	O
+
+However	O
+,	O
+the	O
+removal	O
+of	O
+exons	O
+4	O
+and	O
+5	O
+from	O
+the	O
+CSMD1	O
+transcript	O
+in	O
+PCI	O
+-	O
+13	O
+may	O
+reflect	O
+a	O
+more	O
+specific	O
+phenomenon	O
+than	O
+a	O
+general	O
+inability	O
+to	O
+splice	O
+large	O
+introns	O
+;	O
+this	O
+line	O
+is	O
+still	O
+capable	O
+of	O
+splicing	O
+large	O
+introns	O
+as	O
+evidenced	O
+by	O
+its	O
+successful	O
+splicing	O
+of	O
+exon	O
+3	O
+to	O
+exon	O
+6	O
+,	O
+eliminating	O
+an	O
+intron	O
+of	O
+over	O
+666	O
+kb	O
+.	O
+
+The	O
+failure	O
+to	O
+include	O
+exons	O
+4	O
+and	O
+5	O
+may	O
+be	O
+due	O
+to	O
+inactivation	O
+of	O
+a	O
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+enhancer	O
+in	O
+intron	O
+3	O
+,	O
+or	O
+to	O
+less	O
+efficient	O
+splicing	O
+due	O
+to	O
+the	O
+fact	O
+that	O
+exons	O
+4	O
+and	O
+5	O
+do	O
+not	O
+begin	O
+with	O
+the	O
+consensus	O
+G	O
+residue	O
+(	O
+Figure	O
+4B	O
+)	O
+[	O
+26	O
+]	O
+.	O
+
+Conclusion	O
+
+Taken	O
+together	O
+,	O
+our	O
+data	O
+suggest	O
+that	O
+CSMD1	O
+function	O
+is	O
+lost	O
+in	O
+head	O
+and	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+through	O
+a	O
+variety	O
+of	O
+mechanisms	O
+other	O
+than	O
+point	O
+mutagenesis	O
+.	O
+
+Epigenetic	O
+modifications	O
+of	O
+amplicon	O
+1	O
+and	O
+defective	O
+splicing	O
+appear	O
+to	O
+be	O
+fruitful	O
+areas	O
+to	O
+explore	O
+in	O
+primary	O
+head	O
+and	O
+neck	O
+squamous	O
+cancers	O
+.	O
+
+Methods	O
+
+Cell	O
+lines	O
+and	O
+tissue	O
+samples	O
+
+DNA	O
+from	O
+HNSCC	O
+cell	O
+lines	O
+UMSCC9	O
+,	O
+UMSCC35	O
+,	O
+UMSCC37	O
+,	O
+UMSCC38	O
+,	O
+UMSCC45	O
+,	O
+UMSCC49	O
+,	O
+UMSCC65	O
+,	O
+UMSCC68	O
+,	O
+and	O
+UMSCC76	O
+was	O
+provided	O
+by	O
+Dr	O
+.	O
+Thomas	O
+Carey	O
+,	O
+University	O
+of	O
+Michigan	O
+[	O
+27	O
+]	O
+.	O
+
+Dr	O
+.	O
+Ruud	O
+Brakenhoff	O
+,	O
+Vrije	O
+Universitat	O
+,	O
+provided	O
+cell	O
+lines	O
+040	O
+,	O
+041	O
+,	O
+and	O
+094	O
+[	O
+28	O
+]	O
+;	O
+Dr	O
+.	O
+Theresa	O
+Whiteside	O
+,	O
+University	O
+of	O
+Pittsburgh	O
+,	O
+provided	O
+cell	O
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+PCI	O
+-	O
+1	O
+,	O
+PCI	O
+-	O
+2	O
+,	O
+PCI	O
+-	O
+4B	O
+,	O
+PCI	O
+-	O
+13	O
+,	O
+PCI	O
+-	O
+30	O
+,	O
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+-	O
+50	O
+,	O
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+-	O
+51	O
+,	O
+PCI	O
+-	O
+52	O
+,	O
+PCI	O
+-	O
+100	O
+[	O
+29	O
+]	O
+,	O
+SCC4	O
+,	O
+SCC9	O
+[	O
+30	O
+,	O
+31	O
+]	O
+,	O
+and	O
+UPCI	O
+:	O
+SCC068	O
+,	O
+UPCI	O
+:	O
+SCC74	O
+,	O
+UPCI	O
+:	O
+SCC104	O
+,	O
+UPCI	O
+:	O
+SCC182	O
+,	O
+UPCI	O
+:	O
+SCC203	O
+,	O
+and	O
+UPCI	O
+:	O
+SCC220	O
+[	O
+developed	O
+by	O
+Dr	O
+.	O
+Susanne	O
+Gollin	O
+,	O
+University	O
+of	O
+Pittsburgh	O
+,	O
+32	O
+]	O
+.	O
+
+Dr	O
+.	O
+Gollin	O
+provided	O
+cell	O
+lines	O
+UPCI	O
+:	O
+SCC056	O
+,	O
+UPCI	O
+:	O
+SCC066	O
+,	O
+and	O
+UPCI	O
+:	O
+SCC114	O
+[	O
+14	O
+,	O
+16	O
+,	O
+32	O
+]	O
+.	O
+
+The	O
+immortal	O
+but	O
+untransformed	O
+keratinocyte	O
+line	O
+OKF6	O
+-	O
+TERT1	O
+was	O
+obtained	O
+from	O
+Dr	O
+.	O
+James	O
+Rheinwald	O
+,	O
+Harvard	O
+University	O
+[	O
+20	O
+]	O
+.	O
+
+Normal	O
+oropharyngeal	O
+epithelium	O
+was	O
+isolated	O
+from	O
+discarded	O
+tissue	O
+from	O
+uvulopalatopharyngop	O
+(	O
+UPPP	O
+)	O
+collected	O
+anonymously	O
+with	O
+the	O
+approval	O
+of	O
+the	O
+Washington	O
+University	O
+Human	B
+Studies	O
+Committee	O
+.	O
+
+Cell	O
+Culture	O
+and	O
+Tissue	O
+Preparation	O
+
+Squamous	O
+cell	O
+carcinoma	O
+cell	O
+lines	O
+were	O
+grown	O
+in	O
+DMEM	O
+or	O
+DMEM	O
+:	O
+F	O
+-	O
+12	O
+,	O
+1	O
+:	O
+1	O
+Mixture	O
+(	O
+BioWhittaker	O
+)	O
+containing	O
+10	O
+%	O
+fetal	O
+bovine	B
+serum	O
+(	O
+Sigma	O
+)	O
+.	O
+
+DMEM	O
+medium	O
+was	O
+supplemented	O
+with	O
+1X	O
+MEM	O
+Nonessential	O
+Amino	O
+Acids	O
+(	O
+BioWhittaker	O
+)	O
+.	O
+
+Upper	O
+aerodigestive	O
+tract	O
+epithelium	O
+was	O
+separated	O
+from	O
+the	O
+rest	O
+of	O
+the	O
+UPPP	O
+specimen	O
+by	O
+digestion	O
+with	O
+Dispase	O
+II	O
+(	O
+Roche	O
+)	O
+using	O
+a	O
+protocol	O
+adapted	O
+from	O
+Oda	O
+and	O
+Watson	O
+[	O
+33	O
+]	O
+.	O
+
+Nucleic	O
+acid	O
+preparation	O
+and	O
+bisulfite	O
+conversion	O
+
+Genomic	O
+DNA	O
+was	O
+isolated	O
+by	O
+using	O
+either	O
+Nucleospin	O
+Tissue	O
+kits	O
+(	O
+Clontech	O
+)	O
+,	O
+QIAamp	O
+DNA	O
+Blood	O
+Mini	O
+kits	O
+(	O
+Qiagen	O
+)	O
+or	O
+Trizol	O
+(	O
+Invitrogen	O
+)	O
+according	O
+to	O
+the	O
+manufacturers	O
+'	O
+instructions	O
+.	O
+
+Total	O
+RNA	O
+isolation	O
+,	O
+synthesis	O
+of	O
+first	O
+strand	O
+cDNA	O
+,	O
+RT	O
+-	O
+PCR	O
+and	O
+5	O
+'	O
+RACE	O
+PCR	O
+were	O
+performed	O
+essentially	O
+as	O
+previously	O
+described	O
+[	O
+1	O
+]	O
+.	O
+
+Poly	O
+-	O
+A	O
++	O
+RNA	O
+for	O
+Northern	O
+blotting	O
+was	O
+selected	O
+from	O
+total	O
+RNA	O
+using	O
+Oligotex	O
+beads	O
+(	O
+Qiagen	O
+)	O
+.	O
+
+Northern	O
+blotting	O
+and	O
+hybridization	O
+were	O
+performed	O
+as	O
+previously	O
+described	O
+[	O
+1	O
+]	O
+.	O
+
+cDNA	O
+synthesis	O
+was	O
+primed	O
+using	O
+oligo	O
+dT	O
+or	O
+random	O
+primers	O
+and	O
+extended	O
+by	O
+either	O
+Thermoscript	O
+or	O
+Superscript	O
+III	O
+reverse	O
+transcriptase	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+PCR	O
+was	O
+run	O
+in	O
+Perkin	O
+-	O
+Elmer	O
+480	O
+or	O
+Applied	O
+Biosystems	O
+9700	O
+thermal	O
+cyclers	O
+for	O
+35	O
+cycles	O
+unless	O
+otherwise	O
+noted	O
+.	O
+
+Images	O
+of	O
+ethidium	O
+bromide	O
+stained	O
+gels	O
+were	O
+captured	O
+with	O
+a	O
+Gel	O
+-	O
+Doc	O
+imaging	O
+station	O
+(	O
+Biorad	O
+)	O
+.	O
+
+Quantitative	O
+PCR	O
+was	O
+run	O
+in	O
+an	O
+Applied	O
+Biosystems	O
+5700	O
+thermal	O
+cycler	O
+using	O
+SYBR	O
+Green	O
+Master	O
+Mix	O
+(	O
+Applied	O
+Biosystems	O
+)	O
+.	O
+
+Primers	O
+prm2426	O
+(	O
+gtgtggagtatctgcagaca	O
+)	O
+and	O
+prm2427	O
+(	O
+ctggactaagcctccacagt	O
+)	O
+were	O
+used	O
+to	O
+amplify	O
+a	O
+132	O
+base	O
+segment	O
+spanning	O
+CSMD1	O
+'	O
+s	O
+first	O
+and	O
+second	O
+exons	O
+.	O
+
+An	O
+amplicon	O
+from	O
+human	B
+18S	O
+RNA	O
+was	O
+used	O
+as	O
+a	O
+basis	O
+for	O
+comparisons	O
+across	O
+cell	O
+lines	O
+(	O
+primers	O
+prm2396	O
+,	O
+ttcggaactgaggccatgat	O
+and	O
+prm2397	O
+,	O
+tttcgctctggtccgtcttg	O
+)	O
+.	O
+
+Calculations	O
+were	O
+performed	O
+using	O
+the	O
+Delta	O
+Delta	O
+Ct	O
+method	O
+in	O
+GeneAmp	O
+5700	O
+SDS	O
+software	O
+(	O
+version	O
+1	O
+.	O
+3	O
+)	O
+and	O
+Microsoft	O
+Excel	O
+.	O
+
+Quantitation	O
+was	O
+based	O
+on	O
+the	O
+average	O
+values	O
+obtained	O
+from	O
+duplicate	O
+reactions	O
+.	O
+
+The	O
+level	O
+of	O
+CSMD1	O
+expression	O
+in	O
+normal	O
+oropharyngeal	O
+epithelium	O
+was	O
+determined	O
+from	O
+pooled	O
+cDNA	O
+from	O
+five	O
+UPPP	O
+specimens	O
+.	O
+
+We	O
+used	O
+the	O
+CpGenome	O
+DNA	O
+Modification	O
+kit	O
+(	O
+Intergen	O
+)	O
+for	O
+bisulfite	O
+conversion	O
+of	O
+the	O
+genomic	O
+DNA	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+,	O
+with	O
+the	O
+following	O
+exception	O
+.	O
+
+Incubation	O
+of	O
+the	O
+conversion	O
+reaction	O
+was	O
+carried	O
+out	O
+in	O
+a	O
+thermal	O
+cycler	O
+for	O
+six	O
+cycles	O
+each	O
+consisting	O
+of	O
+three	O
+minutes	O
+at	O
+94	O
+degrees	O
+C	O
+followed	O
+by	O
+three	O
+hours	O
+at	O
+50	O
+degrees	O
+C	O
+(	O
+Christina	O
+Menke	O
+and	O
+Paul	O
+Goodfellow	O
+,	O
+personal	O
+communication	O
+)	O
+.	O
+
+Analysis	O
+of	O
+CSMD1	O
+Promoter	O
+Methylation	O
+
+Methylation	O
+of	O
+three	O
+segments	O
+of	O
+the	O
+CSMD1	O
+CpG	O
+island	O
+was	O
+examined	O
+using	O
+the	O
+Combined	O
+Bisulfite	O
+Restriction	O
+Analysis	O
+technique	O
+(	O
+COBRA	O
+)	O
+[	O
+19	O
+]	O
+.	O
+
+All	O
+three	O
+segments	O
+were	O
+amplified	O
+by	O
+using	O
+the	O
+nested	O
+primers	O
+and	O
+PCR	O
+conditions	O
+listed	O
+in	O
+Table	O
+1	O
+.	O
+
+Amplicon	O
+1	O
+extends	O
+from	O
+-	O
+395	O
+to	O
+-	O
+112	O
+bp	O
+,	O
+amplicon	O
+2	O
+from	O
++	O
+175	O
+to	O
++	O
+396	O
+bp	O
+,	O
+and	O
+amplicon	O
+3	O
+from	O
++	O
+398	O
+to	O
++	O
+718	O
+bp	O
+relative	O
+to	O
+the	O
+first	O
+base	O
+of	O
+the	O
+transcript	O
+.	O
+
+A	O
+small	O
+region	O
+surrounding	O
+the	O
+transcription	O
+start	O
+site	O
+(	O
+-	O
+111	O
+to	O
++	O
+174	O
+bp	O
+)	O
+could	O
+not	O
+be	O
+examined	O
+because	O
+no	O
+PCR	O
+primers	O
+could	O
+be	O
+designed	O
+from	O
+its	O
+extremely	O
+GC	O
+-	O
+rich	O
+sequence	O
+.	O
+
+The	O
+first	O
+round	O
+PCR	O
+used	O
+2	O
+mu	O
+l	O
+of	O
+bisulfite	O
+converted	O
+genomic	O
+DNA	O
+in	O
+a	O
+final	O
+volume	O
+of	O
+10	O
+mu	O
+l	O
+.	O
+
+Subsequent	O
+amplifications	O
+with	O
+nested	O
+primers	O
+used	O
+4	O
+mu	O
+l	O
+of	O
+first	O
+round	O
+product	O
+as	O
+template	O
+in	O
+reactions	O
+with	O
+a	O
+final	O
+volume	O
+of	O
+20	O
+mu	O
+l	O
+.	O
+
+All	O
+PCR	O
+was	O
+carried	O
+out	O
+for	O
+35	O
+cycles	O
+.	O
+
+A	O
+portion	O
+of	O
+the	O
+second	O
+round	O
+PCR	O
+product	O
+was	O
+run	O
+on	O
+a	O
+1	O
+.	O
+5	O
+%	O
+agarose	O
+gel	O
+,	O
+stained	O
+with	O
+ethidium	O
+bromide	O
+,	O
+and	O
+quantified	O
+using	O
+the	O
+ImageQuant	O
+software	O
+package	O
+(	O
+v1	O
+.	O
+2	O
+for	O
+Macintosh	O
+,	O
+Molecular	O
+Dynamics	O
+)	O
+so	O
+that	O
+equal	O
+amounts	O
+of	O
+each	O
+could	O
+be	O
+used	O
+in	O
+restriction	O
+digests	O
+.	O
+
+Restriction	O
+digests	O
+for	O
+COBRA	O
+were	O
+performed	O
+with	O
+either	O
+BstU	O
+I	O
+or	O
+Taq	O
+alpha	O
+I	O
+(	O
+5	O
+or	O
+10	O
+units	O
+per	O
+reaction	O
+,	O
+respectively	O
+;	O
+New	O
+England	O
+Biolabs	O
+)	O
+for	O
+4	O
+hours	O
+in	O
+a	O
+final	O
+volume	O
+of	O
+10	O
+mu	O
+l	O
+.	O
+
+Taq	O
+alpha	O
+I	O
+digests	O
+were	O
+performed	O
+only	O
+when	O
+no	O
+methylation	O
+was	O
+detected	O
+with	O
+BstU	O
+I	O
+.	O
+
+BstU	O
+I	O
+digests	O
+also	O
+included	O
+an	O
+internal	O
+control	O
+DNA	O
+fragment	O
+to	O
+confirm	O
+complete	O
+digestion	O
+.	O
+
+This	O
+DNA	O
+fragment	O
+contains	O
+a	O
+single	O
+BstU	O
+I	O
+site	O
+and	O
+was	O
+amplified	O
+from	O
+a	O
+cloned	O
+CSMD1	O
+cDNA	O
+using	O
+primers	O
+prm2020	O
+(	O
+agatcccccagtgtctccct	O
+)	O
+and	O
+prm2021	O
+(	O
+actgctggtgccgtggtaat	O
+)	O
+.	O
+
+The	O
+control	O
+PCR	O
+product	O
+is	O
+1019	O
+bp	O
+long	O
+and	O
+is	O
+digested	O
+to	O
+two	O
+fragments	O
+of	O
+605	O
+and	O
+414	O
+bp	O
+by	O
+BstU	O
+I	O
+.	O
+
+Digestion	O
+products	O
+were	O
+fractionated	O
+on	O
+a	O
+10	O
+%	O
+polyacrylamide	O
+gel	O
+,	O
+stained	O
+with	O
+ethidium	O
+bromide	O
+,	O
+and	O
+visualized	O
+with	O
+a	O
+Gel	O
+-	O
+Doc	O
+video	O
+imaging	O
+workstation	O
+(	O
+Bio	O
+-	O
+Rad	O
+)	O
+.	O
+
+High	O
+resolution	O
+analysis	O
+of	O
+methylation	O
+was	O
+performed	O
+by	O
+sequence	O
+analysis	O
+of	O
+individual	O
+clones	O
+from	O
+amplicons	O
+1	O
+and	O
+2	O
+.	O
+
+DNA	O
+from	O
+amplicon	O
+3	O
+proved	O
+unclonable	O
+and	O
+gel	O
+electrophoresis	O
+suggests	O
+that	O
+its	O
+very	O
+AT	O
+rich	O
+sequence	O
+results	O
+in	O
+a	O
+bent	O
+DNA	O
+configuration	O
+.	O
+
+PCR	O
+products	O
+were	O
+purified	O
+using	O
+the	O
+Nucleospin	O
+Extraction	O
+columns	O
+(	O
+Clontech	O
+)	O
+and	O
+inserted	O
+into	O
+the	O
+pCR2	O
+.	O
+1	O
+-	O
+TOPO	O
+vector	O
+using	O
+the	O
+TOPO	O
+TA	O
+Cloning	O
+kit	O
+(	O
+Invitrogen	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+.	O
+
+Plasmid	O
+DNA	O
+from	O
+individual	O
+colonies	O
+was	O
+isolated	O
+using	O
+the	O
+Nucleospin	O
+Plus	O
+Plasmid	O
+Miniprep	O
+kit	O
+(	O
+Clontech	O
+)	O
+and	O
+sequenced	O
+with	O
+a	O
+reverse	O
+vector	O
+primer	O
+(	O
+agcggataacaatttcacac	O
+)	O
+using	O
+fluorescence	O
+based	O
+sequencing	O
+with	O
+Big	O
+Dye	O
+Terminator	O
+mix	O
+(	O
+Applied	O
+Biosystems	O
+)	O
+.	O
+
+Treatment	O
+of	O
+cultured	O
+cells	O
+with	O
+DNA	O
+methyltransferase	O
+inhibitors	O
+
+Cell	O
+line	O
+094	O
+was	O
+treated	O
+with	O
+5	O
+-	O
+aza	O
+-	O
+2	O
+'	O
+-	O
+deoxycytidine	O
+(	O
+5aza	O
+-	O
+dC	O
+)	O
+(	O
+Sigma	O
+)	O
+dissolved	O
+in	O
+DMSO	O
+.	O
+
+Two	O
+100	O
+mm	O
+cell	O
+culture	O
+dishes	O
+containing	O
+5	O
+x	O
+105	O
+cells	O
+were	O
+established	O
+for	O
+each	O
+of	O
+the	O
+drug	O
+concentrations	O
+tested	O
+.	O
+
+Cells	O
+were	O
+grown	O
+for	O
+72	O
+hours	O
+in	O
+media	O
+containing	O
+DMEM	O
+:	O
+F	O
+-	O
+12	O
+,	O
+1	O
+:	O
+1	O
+Mixture	O
+(	O
+BioWhittaker	O
+)	O
+with	O
+1X	O
+MEM	O
+Nonessential	O
+Amino	O
+Acids	O
+(	O
+BioWhittaker	O
+)	O
+and	O
+10	O
+%	O
+fetal	O
+bovine	B
+serum	O
+and	O
+then	O
+switched	O
+to	O
+media	O
+containing	O
+5aza	O
+-	O
+dC	O
+at	O
+concentrations	O
+of	O
+0	O
+mu	O
+m	O
+,	O
+5	O
+mu	O
+M	O
+,	O
+25	O
+mu	O
+M	O
+,	O
+or	O
+100	O
+mu	O
+M	O
+.	O
+
+Cells	O
+were	O
+fed	O
+daily	O
+for	O
+4	O
+-	O
+5	O
+days	O
+and	O
+then	O
+both	O
+plates	O
+were	O
+harvested	O
+in	O
+3	O
+ml	O
+of	O
+Trizol	O
+(	O
+Invitrogen	O
+)	O
+for	O
+isolation	O
+of	O
+RNA	O
+and	O
+DNA	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+.	O
+
+RT	O
+-	O
+PCR	O
+used	O
+for	O
+detection	O
+of	O
+CSMD1	O
+transcripts	O
+in	O
+these	O
+treated	O
+cells	O
+was	O
+run	O
+for	O
+40	O
+cycles	O
+.	O
+
+Abbreviations	O
+
+5aza	O
+-	O
+dC	O
+=	O
+5	O
+-	O
+aza	O
+-	O
+2	O
+'	O
+deoxycytidine	O
+,	O
+COBRA	O
+=	O
+Combined	O
+Bisulfite	O
+Restriction	O
+Analysis	O
+,	O
+CSMD1	O
+=	O
+Cub	O
+and	O
+sushi	O
+multiple	O
+domains	O
+1	O
+,	O
+HNSCC	O
+=	O
+head	O
+&	O
+neck	O
+squamous	O
+cell	O
+carcinoma	O
+,	O
+RT	O
+-	O
+PCR	O
+=	O
+reverse	O
+transcription	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+,	O
+SCC	O
+=	O
+squamous	O
+cell	O
+carcinoma	O
+,	O
+UPPP	O
+=	O
+uvulopalatopharyngop	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+
+Authors	O
+'	O
+contributions	O
+
+TMR	O
+performed	O
+the	O
+DNA	O
+methylation	O
+analysis	O
+,	O
+and	O
+parts	O
+of	O
+the	O
+transcript	O
+survey	O
+.	O
+
+BDT	O
+cloned	O
+and	O
+characterized	O
+the	O
+novel	O
+first	O
+exon	O
+expressed	O
+in	O
+cell	O
+line	O
+SCC9	O
+.	O
+
+SBS	O
+performed	O
+parts	O
+of	O
+the	O
+transcript	O
+survey	O
+and	O
+characterized	O
+the	O
+deletion	O
+of	O
+exons	O
+4	O
+and	O
+5	O
+in	O
+PCI	O
+-	O
+13	O
+.	O
+
+All	O
+three	O
+authors	O
+participated	O
+in	O
+the	O
+analysis	O
+of	O
+the	O
+data	O
+and	O
+in	O
+the	O
+writing	O
+of	O
+the	O
+manuscript	O
+.	O
+
+Plasma	O
+D	O
+-	O
+dimer	O
+concentration	O
+in	O
+patients	B
+with	O
+systemic	O
+sclerosis	O
+
+Abstract	O
+
+Background	O
+
+Systemic	O
+sclerosis	O
+(	O
+SSc	O
+)	O
+is	O
+an	O
+autoimmune	O
+disorder	O
+of	O
+the	O
+connective	O
+tissue	O
+characterized	O
+by	O
+widespread	O
+vascular	O
+lesions	O
+and	O
+fibrosis	O
+.	O
+
+Little	O
+is	O
+known	O
+so	O
+far	O
+on	O
+the	O
+activation	O
+of	O
+the	O
+hemostatic	O
+and	O
+fibrinolytic	O
+systems	O
+in	O
+SSc	O
+,	O
+and	O
+most	O
+preliminary	O
+evidences	O
+are	O
+discordant	O
+.	O
+
+Methods	O
+
+To	O
+verify	O
+whether	O
+SSc	O
+patients	B
+might	O
+display	O
+a	O
+prothrombotic	O
+condition	O
+,	O
+plasma	O
+D	O
+-	O
+dimer	O
+was	O
+assessed	O
+in	O
+28	O
+consecutive	O
+SSc	O
+patients	B
+and	O
+in	O
+33	O
+control	O
+subjects	O
+,	O
+matched	O
+for	O
+age	O
+,	O
+sex	O
+and	O
+environmental	O
+habit	O
+.	O
+
+Results	O
+and	O
+discussion	O
+
+When	O
+compared	O
+to	O
+healthy	O
+controls	O
+,	O
+geometric	O
+mean	O
+and	O
+95	O
+%	O
+confidence	O
+interval	O
+(	O
+IC95	O
+%	O
+)	O
+of	O
+plasma	O
+D	O
+-	O
+dimer	O
+were	O
+significantly	O
+increased	O
+in	O
+SSc	O
+patients	B
+(	O
+362	O
+ng	O
+/	O
+mL	O
+,	O
+IC	O
+95	O
+%	O
+:	O
+361	O
+-	O
+363	O
+ng	O
+/	O
+mL	O
+vs	O
+229	O
+ng	O
+/	O
+mL	O
+,	O
+IC95	O
+%	O
+:	O
+228	O
+-	O
+231	O
+ng	O
+/	O
+mL	O
+,	O
+p	O
+=	O
+0	O
+.	O
+005	O
+)	O
+.	O
+
+After	O
+stratifying	O
+SSc	O
+patients	B
+according	O
+to	O
+disease	O
+subset	O
+,	O
+no	O
+significant	O
+differences	O
+were	O
+observed	O
+between	O
+those	O
+with	O
+limited	O
+cutaneous	O
+pattern	O
+and	O
+controls	O
+,	O
+whereas	O
+patients	B
+with	O
+diffuse	O
+cutaneous	O
+pattern	O
+displayed	O
+substantially	O
+increased	O
+values	O
+.	O
+
+No	O
+correlation	O
+was	O
+found	O
+between	O
+plasma	O
+D	O
+-	O
+dimer	O
+concentration	O
+and	O
+age	O
+,	O
+sex	O
+,	O
+autoantibody	O
+pattern	O
+,	O
+serum	O
+creatinine	O
+,	O
+erythrosedimentation	O
+rate	O
+,	O
+nailfold	O
+videocapillaroscopic	O
+pattern	O
+and	O
+pulmonary	O
+involvement	O
+.	O
+
+Conclusion	O
+
+We	O
+demonstrated	O
+that	O
+SSc	O
+patients	B
+with	O
+diffuse	O
+subset	O
+are	O
+characterized	O
+by	O
+increased	O
+plasma	O
+D	O
+-	O
+dimer	O
+values	O
+,	O
+reflecting	O
+a	O
+potential	O
+activation	O
+of	O
+both	O
+the	O
+hemostatic	O
+and	O
+fibrinolytic	O
+cascades	O
+,	O
+which	O
+might	O
+finally	O
+predispose	O
+these	O
+patients	B
+to	O
+thrombotic	O
+complications	O
+.	O
+
+Background	O
+
+Systemic	O
+sclerosis	O
+(	O
+SSc	O
+)	O
+is	O
+an	O
+autoimmune	O
+disorder	O
+of	O
+the	O
+connective	O
+tissue	O
+characterized	O
+by	O
+widespread	O
+vascular	O
+lesions	O
+and	O
+fibrosis	O
+.	O
+
+In	O
+SSc	O
+,	O
+vasospasm	O
+causes	O
+frequent	O
+episodes	O
+of	O
+reperfusion	O
+injury	O
+and	O
+free	O
+radical	O
+-	O
+mediated	O
+endothelial	O
+dysfunction	O
+,	O
+which	O
+might	O
+finally	O
+influence	O
+the	O
+onset	O
+of	O
+local	O
+thrombotic	O
+complications	O
+.	O
+
+The	O
+characteristic	O
+vascular	O
+involvement	O
+affects	O
+primarily	O
+small	O
+arteries	O
+and	O
+capillaries	O
+,	O
+causing	O
+reduced	O
+blood	O
+flow	O
+and	O
+tissue	O
+ischemia	O
+and	O
+supporting	O
+the	O
+typical	O
+clinical	O
+manifestations	O
+of	O
+this	O
+unique	O
+autoimmune	O
+disorder	O
+[	O
+1	O
+]	O
+.	O
+
+However	O
+,	O
+mechanisms	O
+involved	O
+in	O
+the	O
+endothelial	O
+injury	O
+are	O
+as	O
+yet	O
+elusive	O
+and	O
+most	O
+biochemical	O
+evidences	O
+are	O
+often	O
+inconclusive	O
+or	O
+controversial	O
+.	O
+
+Some	O
+earlier	O
+investigations	O
+suggested	O
+that	O
+SSc	O
+patients	B
+might	O
+be	O
+characterized	O
+by	O
+a	O
+procoagulant	O
+state	O
+,	O
+reporting	O
+depressed	O
+basal	O
+and	O
+stimulated	O
+fibrinolytic	O
+activity	O
+,	O
+while	O
+others	O
+studies	O
+have	O
+reported	O
+normal	O
+plasma	O
+fibrinolytic	O
+activity	O
+and	O
+normal	O
+skin	O
+and	O
+plasma	O
+tissue	O
+plasminogen	O
+activator	O
+(	O
+tPA	O
+)	O
+levels	O
+[	O
+2	O
+-	O
+4	O
+]	O
+.	O
+
+It	O
+has	O
+been	O
+also	O
+reported	O
+that	O
+the	O
+lack	O
+of	O
+a	O
+consistent	O
+and	O
+homogenous	O
+increase	O
+of	O
+some	O
+fibrinolytic	O
+markers	O
+,	O
+in	O
+the	O
+presence	O
+of	O
+normal	O
+levels	O
+of	O
+antithrombin	O
+,	O
+might	O
+indirectly	O
+highlight	O
+an	O
+impairment	O
+of	O
+the	O
+heparan	O
+sulphate	O
+-	O
+antithrombin	O
+system	O
+,	O
+which	O
+would	O
+finally	O
+promote	O
+thrombin	O
+generation	O
+[	O
+3	O
+]	O
+.	O
+
+Conversely	O
+,	O
+Cerinic	O
+and	O
+colleagues	O
+provided	O
+evidence	O
+that	O
+fibrinolysis	O
+might	O
+be	O
+impaired	O
+in	O
+SSc	O
+,	O
+as	O
+shown	O
+by	O
+reduced	O
+D	O
+-	O
+dimer	O
+and	O
+decreased	O
+levels	O
+of	O
+plasminogen	O
+activator	O
+inhibitor	O
+[	O
+4	O
+]	O
+.	O
+
+In	O
+synthesis	O
+,	O
+there	O
+are	O
+no	O
+conclusive	O
+evidences	O
+on	O
+the	O
+activity	O
+of	O
+the	O
+hemostatic	O
+and	O
+fibrinolytic	O
+pathways	O
+in	O
+SSc	O
+so	O
+far	O
+.	O
+
+D	O
+-	O
+dimer	O
+,	O
+a	O
+breakdown	O
+product	O
+of	O
+cross	O
+-	O
+linked	O
+fibrin	O
+,	O
+was	O
+proven	O
+useful	O
+for	O
+the	O
+diagnostic	O
+evaluation	O
+of	O
+several	O
+thrombotic	O
+disorders	O
+.	O
+
+Moreover	O
+,	O
+an	O
+increased	O
+D	O
+-	O
+dimer	O
+value	O
+in	O
+plasma	O
+is	O
+a	O
+reliable	O
+marker	O
+of	O
+a	O
+systemic	O
+prothrombotic	O
+state	O
+,	O
+likely	O
+superior	O
+to	O
+alternative	O
+fibrinolytic	O
+markers	O
+,	O
+and	O
+its	O
+measurement	O
+might	O
+be	O
+helpful	O
+in	O
+predicting	O
+or	O
+preventing	O
+thrombotic	O
+events	O
+in	O
+the	O
+single	O
+patient	B
+[	O
+5	O
+]	O
+.	O
+
+Therefore	O
+,	O
+to	O
+investigate	O
+whether	O
+SSc	O
+patients	B
+might	O
+be	O
+characterized	O
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+prothrombotic	O
+condition	O
+,	O
+plasma	O
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+-	O
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+vales	O
+were	O
+measured	O
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+a	O
+subset	O
+of	O
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+patients	B
+,	O
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+with	O
+those	O
+of	O
+a	O
+healthy	O
+matched	O
+control	O
+population	O
+and	O
+further	O
+associated	O
+with	O
+SSc	O
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+.	O
+
+Methods	O
+
+Plasma	O
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+-	O
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+measured	O
+in	O
+28	O
+consecutive	O
+SSc	O
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+(	O
+2	O
+males	O
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+26	O
+females	O
+;	O
+mean	O
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+50	O
++	O
+/	O
+-	O
+15	O
+years	O
+,	O
+17	O
+with	O
+limited	O
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+11	O
+with	O
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+disease	O
+patterns	O
+)	O
+,	O
+who	O
+fulfilled	O
+the	O
+American	O
+Rheumatism	O
+Association	O
+'	O
+s	O
+criteria	O
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+the	O
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+SSc	O
+[	O
+6	O
+]	O
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+33	O
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+subjects	O
+,	O
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+for	O
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+(	O
+48	O
++	O
+/	O
+-	O
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+)	O
+,	O
+sex	O
+(	O
+3	O
+males	O
+,	O
+30	O
+females	O
+)	O
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+environmental	O
+habit	O
+,	O
+recruited	O
+among	O
+healthy	O
+hospital	O
+personnel	O
+.	O
+
+Samples	O
+were	O
+collected	O
+in	O
+the	O
+morning	O
+;	O
+all	O
+subjects	O
+were	O
+in	O
+a	O
+fasted	O
+state	O
+.	O
+
+The	O
+research	O
+was	O
+carried	O
+out	O
+according	O
+to	O
+the	O
+principles	O
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+the	O
+Declaration	O
+of	O
+Helsinki	O
+and	O
+an	O
+informed	O
+consent	O
+for	O
+testing	O
+was	O
+received	O
+from	O
+all	O
+individuals	O
+recruited	O
+to	O
+the	O
+study	O
+.	O
+
+Blood	O
+was	O
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+after	O
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+overnight	O
+fast	O
+into	O
+siliconized	O
+vacuum	O
+tubes	O
+,	O
+containing	O
+0	O
+.	O
+105	O
+mol	O
+/	O
+l	O
+sodium	O
+citrate	O
+(	O
+Becton	O
+-	O
+Dickinson	O
+,	O
+Oxford	O
+,	O
+UK	O
+)	O
+.	O
+
+Samples	O
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+gently	O
+mixed	O
+and	O
+centrifuged	O
+for	O
+10	O
+min	O
+at	O
+15	O
+degrees	O
+C	O
+at	O
+1500	O
+x	O
+g	O
+;	O
+plasma	O
+was	O
+separated	O
+and	O
+stored	O
+in	O
+aliquots	O
+at	O
+-	O
+70	O
+degrees	O
+C	O
+until	O
+measurement	O
+.	O
+
+Plasma	O
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+-	O
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+measured	O
+employing	O
+Vidas	O
+DD	O
+,	O
+a	O
+rapid	O
+and	O
+quantitative	O
+automated	O
+enzyme	O
+linked	O
+immunosorbent	O
+assay	O
+with	O
+fluorescent	O
+detection	O
+,	O
+on	O
+the	O
+Mini	O
+Vidas	O
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+(	O
+bioMerieux	O
+,	O
+Marcy	O
+l	O
+'	O
+Etoile	O
+,	O
+France	O
+)	O
+.	O
+
+Analytical	O
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+,	O
+expressed	O
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+terms	O
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+-	O
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+(	O
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+)	O
+,	O
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+manufacturer	O
+as	O
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+
+Significance	O
+of	O
+differences	O
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+samples	O
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+,	O
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+logarithmic	O
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+,	O
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+(	O
+Student	O
+'	O
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+-	O
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+,	O
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+,	O
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+)	O
+;	O
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+level	O
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+0	O
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+.	O
+
+Results	O
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+
+When	O
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+(	O
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+,	O
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+
+After	O
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+(	O
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+-	O
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+:	O
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+/	O
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+,	O
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+(	O
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+(	O
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+-	O
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+/	O
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+,	O
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+-	O
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+/	O
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+;	O
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+<	O
+0	O
+.	O
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+
+Additionally	O
+,	O
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+Group	O
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+,	O
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+inactive	O
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+(	O
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+=	O
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+.	O
+
+As	O
+further	O
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+1	O
+,	O
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+-	O
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+significantly	O
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+modified	O
+Rodnan	O
+total	O
+skin	O
+score	O
+(	O
+TSS	O
+)	O
+and	O
+the	O
+forced	O
+vital	O
+capacity	O
+(	O
+FVC	O
+)	O
+.	O
+
+No	O
+correlation	O
+was	O
+observed	O
+between	O
+plasma	O
+D	O
+-	O
+dimer	O
+concentration	O
+and	O
+age	O
+,	O
+sex	O
+,	O
+autoantibody	O
+pattern	O
+,	O
+serum	O
+creatinine	O
+,	O
+erythrosedimentation	O
+rate	O
+,	O
+nailfold	O
+videocapillaroscopic	O
+pattern	O
+and	O
+pulmonary	O
+involvement	O
+,	O
+ascertained	O
+according	O
+to	O
+the	O
+score	O
+proposed	O
+by	O
+Medsger	O
+et	O
+al	O
+[	O
+8	O
+]	O
+.	O
+
+The	O
+pathogenesis	O
+of	O
+the	O
+endothelial	O
+injury	O
+in	O
+SSc	O
+is	O
+as	O
+yet	O
+elusive	O
+and	O
+most	O
+biochemical	O
+evidences	O
+are	O
+often	O
+inconclusive	O
+or	O
+controversial	O
+.	O
+
+Although	O
+endothelial	O
+cell	O
+apoptosis	O
+and	O
+impaired	O
+angiogenesis	O
+have	O
+received	O
+major	O
+attention	O
+among	O
+the	O
+mechanisms	O
+involved	O
+in	O
+the	O
+characteristic	O
+vascular	O
+dysfunction	O
+,	O
+recent	O
+studies	O
+provided	O
+clear	O
+evidence	O
+of	O
+a	O
+significant	O
+activation	O
+of	O
+the	O
+coagulation	O
+cascade	O
+,	O
+resulting	O
+in	O
+a	O
+procoagulant	O
+state	O
+that	O
+might	O
+finally	O
+raise	O
+the	O
+relative	O
+risk	O
+of	O
+thrombotic	O
+events	O
+in	O
+these	O
+patients	B
+.	O
+
+In	O
+SSc	O
+,	O
+the	O
+peculiar	O
+vascular	O
+lesions	O
+and	O
+fibrosis	O
+were	O
+claimed	O
+to	O
+impair	O
+endothelial	O
+function	O
+,	O
+as	O
+suggested	O
+by	O
+impairment	O
+of	O
+fibrinolysis	O
+and	O
+activation	O
+of	O
+the	O
+coagulation	O
+pathway	O
+.	O
+
+The	O
+following	O
+loss	O
+of	O
+the	O
+balance	O
+between	O
+fibrinolysis	O
+and	O
+coagulation	O
+might	O
+finally	O
+contribute	O
+to	O
+vessel	O
+engulfment	O
+with	O
+fibrin	O
+and	O
+breakdown	O
+of	O
+vessel	O
+patency	O
+,	O
+symptomatic	O
+of	O
+a	O
+tendency	O
+to	O
+the	O
+development	O
+of	O
+thrombotic	O
+complications	O
+in	O
+this	O
+particular	O
+autoimmune	O
+disorder	O
+[	O
+4	O
+]	O
+.	O
+
+D	O
+-	O
+dimer	O
+is	O
+a	O
+heterogeneous	O
+class	O
+of	O
+end	O
+-	O
+stage	O
+degradation	O
+products	O
+that	O
+directly	O
+reflect	O
+the	O
+level	O
+of	O
+lysed	O
+cross	O
+-	O
+linked	O
+fibrin	O
+,	O
+occurring	O
+in	O
+vivo	O
+with	O
+a	O
+wide	O
+range	O
+of	O
+molecular	O
+weights	O
+.	O
+
+Therefore	O
+,	O
+D	O
+-	O
+dimer	O
+is	O
+a	O
+well	O
+-	O
+recognized	O
+marker	O
+of	O
+a	O
+systemic	O
+prothrombotic	O
+state	O
+[	O
+5	O
+,	O
+9	O
+]	O
+and	O
+appears	O
+a	O
+strong	O
+,	O
+consistent	O
+predictor	O
+of	O
+cardiovascular	O
+events	O
+in	O
+the	O
+general	O
+population	O
+,	O
+in	O
+patients	B
+with	O
+cardiovascular	O
+disease	O
+and	O
+in	O
+other	O
+pathologies	O
+characterized	O
+by	O
+an	O
+increased	O
+risk	O
+of	O
+thrombosis	O
+[	O
+10	O
+-	O
+12	O
+]	O
+.	O
+
+Accordingly	O
+,	O
+D	O
+-	O
+dimer	O
+measurement	O
+could	O
+be	O
+reliably	O
+used	O
+as	O
+an	O
+initial	O
+screening	O
+test	O
+in	O
+patients	B
+with	O
+clinically	O
+suspected	O
+thrombosis	O
+,	O
+as	O
+its	O
+high	O
+negative	O
+predictive	O
+value	O
+enables	O
+to	O
+validly	O
+rule	O
+out	O
+ongoing	O
+thrombotic	O
+complications	O
+[	O
+12	O
+]	O
+.	O
+
+Little	O
+is	O
+known	O
+on	O
+the	O
+thrombotic	O
+tendency	O
+of	O
+SSc	O
+patients	B
+so	O
+far	O
+[	O
+13	O
+]	O
+.	O
+
+At	O
+variance	O
+with	O
+previous	O
+investigations	O
+[	O
+2	O
+-	O
+4	O
+]	O
+,	O
+we	O
+demonstrated	O
+that	O
+SSc	O
+patients	B
+with	O
+diffuse	O
+subset	O
+are	O
+characterized	O
+by	O
+increased	O
+plasma	O
+D	O
+-	O
+dimer	O
+values	O
+,	O
+reflecting	O
+a	O
+potential	O
+activation	O
+of	O
+both	O
+the	O
+coagulation	O
+and	O
+fibrinolytic	O
+pathways	O
+.	O
+
+Conclusion	O
+
+Although	O
+increased	O
+D	O
+-	O
+dimer	O
+values	O
+in	O
+SSc	O
+patients	B
+were	O
+occasionally	O
+observed	O
+in	O
+earlier	O
+studies	O
+,	O
+the	O
+association	O
+between	O
+plasma	O
+D	O
+-	O
+dimer	O
+and	O
+disease	O
+subset	O
+is	O
+likely	O
+an	O
+original	O
+and	O
+innovative	O
+issue	O
+.	O
+
+The	O
+significant	O
+correlation	O
+observed	O
+with	O
+disease	O
+activity	O
+,	O
+cutaneous	O
+involvement	O
+and	O
+forced	O
+vital	O
+capacity	O
+,	O
+further	O
+suggests	O
+that	O
+SSc	O
+patients	B
+,	O
+especially	O
+those	O
+with	O
+diffuse	O
+subset	O
+,	O
+display	O
+a	O
+hypercoagulable	O
+state	O
+,	O
+which	O
+might	O
+finally	O
+predispose	O
+this	O
+peculiar	O
+subset	O
+of	O
+patients	B
+to	O
+the	O
+development	O
+of	O
+thrombotic	O
+complications	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+GL	O
+:	O
+conceived	O
+of	O
+the	O
+study	O
+,	O
+participated	O
+in	O
+its	O
+design	O
+and	O
+coordination	O
+and	O
+drafted	O
+the	O
+manuscript	O
+;	O
+AV	O
+:	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+,	O
+performed	O
+the	O
+statistical	O
+analysis	O
+and	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+;	O
+PC	O
+:	O
+participated	O
+in	O
+the	O
+design	O
+and	O
+coordination	O
+of	O
+the	O
+study	O
+;	O
+GLS	O
+:	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+;	O
+MM	O
+:	O
+participated	O
+in	O
+the	O
+design	O
+and	O
+coordination	O
+of	O
+the	O
+study	O
+and	O
+performed	O
+the	O
+measurement	O
+;	O
+GCG	O
+:	O
+participated	O
+in	O
+the	O
+design	O
+and	O
+coordination	O
+of	O
+the	O
+study	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+The	O
+authors	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Enp1	O
+,	O
+a	O
+yeast	B
+protein	O
+associated	O
+with	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+,	O
+is	O
+required	O
+for	O
+pre	O
+-	O
+rRNA	O
+processing	O
+and	O
+40S	O
+subunit	O
+synthesis	O
+
+Abstract	O
+
+ENP1	O
+is	O
+an	O
+essential	O
+Saccharomyces	B
+cerevisiae	I
+gene	O
+encoding	O
+a	O
+483	O
+amino	O
+acid	O
+polypeptide	O
+.	O
+
+Enp1	O
+protein	O
+is	O
+localized	O
+in	O
+the	O
+nucleus	O
+and	O
+concentrated	O
+in	O
+the	O
+nucleolus	O
+.	O
+
+An	O
+enp1	O
+-	O
+1	O
+temperature	O
+-	O
+sensitive	O
+mutant	O
+inhibited	O
+35S	O
+pre	O
+-	O
+rRNA	O
+early	O
+processing	O
+at	O
+sites	O
+A0	O
+,	O
+A1	O
+and	O
+A2	O
+as	O
+shown	O
+by	O
+northern	O
+analysis	O
+of	O
+steady	O
+state	O
+levels	O
+of	O
+rRNA	O
+precursors	O
+.	O
+
+Pulse	O
+-	O
+chase	O
+analysis	O
+further	O
+revealed	O
+that	O
+the	O
+enp1	O
+-	O
+1	O
+strain	O
+was	O
+defective	O
+in	O
+the	O
+synthesis	O
+of	O
+20S	O
+pre	O
+-	O
+rRNA	O
+and	O
+hence	O
+18S	O
+rRNA	O
+,	O
+which	O
+led	O
+to	O
+reduced	O
+formation	O
+of	O
+40S	O
+ribosomal	O
+subunits	O
+.	O
+
+Co	O
+-	O
+precipitation	O
+analysis	O
+revealed	O
+that	O
+Enp1	O
+was	O
+associated	O
+with	O
+Nop1	O
+protein	O
+,	O
+as	O
+well	O
+as	O
+with	O
+U3	O
+and	O
+U14	O
+RNAs	O
+,	O
+two	O
+snoRNAs	O
+implicated	O
+in	O
+early	O
+pre	O
+-	O
+rRNA	O
+processing	O
+steps	O
+.	O
+
+These	O
+results	O
+suggest	O
+a	O
+direct	O
+role	O
+for	O
+Enp1	O
+in	O
+the	O
+early	O
+steps	O
+of	O
+rRNA	O
+processing	O
+.	O
+
+INTRODUCTION	O
+
+Ribosome	O
+biogenesis	O
+is	O
+one	O
+of	O
+the	O
+major	O
+cellular	O
+activities	O
+in	O
+eukaryotic	O
+cells	O
+.	O
+
+It	O
+takes	O
+place	O
+primarily	O
+in	O
+a	O
+specialized	O
+subnuclear	O
+compartment	O
+,	O
+the	O
+nucleolus	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+In	O
+the	O
+yeast	B
+Saccharomyces	B
+cerevisiae	I
+,	O
+each	O
+rRNA	O
+gene	O
+is	O
+transcribed	O
+by	O
+RNA	O
+polymerase	O
+I	O
+into	O
+a	O
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+precursor	O
+,	O
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+of	O
+18S	O
+,	O
+5	O
+.	O
+8S	O
+and	O
+25S	O
+rRNA	O
+sequences	O
+flanked	O
+by	O
+two	O
+external	O
+transcribed	O
+spacers	O
+(	O
+ETS	O
+)	O
+and	O
+separated	O
+by	O
+two	O
+internal	O
+transcribed	O
+spacers	O
+(	O
+ITS	O
+)	O
+(	O
+Fig	O
+.	O
+1	O
+)	O
+.	O
+
+This	O
+35S	O
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+goes	O
+through	O
+a	O
+series	O
+of	O
+modifications	O
+and	O
+processing	O
+steps	O
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+,	O
+5	O
+.	O
+8S	O
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+.	O
+
+The	O
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+occurs	O
+first	O
+at	O
+sites	O
+A0	O
+,	O
+A1	O
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+A2	O
+,	O
+resulting	O
+in	O
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+-	O
+rRNA	O
+and	O
+27SA2	O
+pre	O
+-	O
+rRNA	O
+.	O
+
+The	O
+20S	O
+pre	O
+-	O
+rRNA	O
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+then	O
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+,	O
+leading	O
+to	O
+the	O
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+18S	O
+rRNA	O
+found	O
+in	O
+the	O
+40S	O
+ribosomal	O
+subunit	O
+.	O
+
+The	O
+27SA2	O
+pre	O
+-	O
+rRNA	O
+is	O
+processed	O
+through	O
+two	O
+alternative	O
+pathways	O
+.	O
+
+The	O
+majority	O
+of	O
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+pre	O
+-	O
+rRNA	O
+is	O
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+at	O
+sites	O
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+and	O
+B2	O
+to	O
+form	O
+the	O
+27SA3	O
+pre	O
+-	O
+rRNA	O
+,	O
+which	O
+is	O
+subsequently	O
+processed	O
+to	O
+produce	O
+27SBS	O
+.	O
+
+Alternatively	O
+,	O
+27SA2	O
+pre	O
+-	O
+rRNA	O
+can	O
+be	O
+processed	O
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+B1L	O
+and	O
+B2	O
+to	O
+generate	O
+27SBL	O
+pre	O
+-	O
+rRNA	O
+.	O
+
+Both	O
+27SBS	O
+and	O
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+-	O
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+then	O
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+at	O
+sites	O
+C1	O
+and	O
+C2	O
+to	O
+generate	O
+the	O
+mature	O
+25S	O
+rRNA	O
+,	O
+and	O
+7SS	O
+or	O
+7SL	O
+intermediates	O
+,	O
+which	O
+are	O
+then	O
+processed	O
+to	O
+mature	O
+5	O
+.	O
+8SS	O
+or	O
+5	O
+.	O
+8SL	O
+rRNAs	O
+(	O
+Fig	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+25S	O
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+and	O
+5	O
+.	O
+8S	O
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+the	O
+RNA	O
+components	O
+of	O
+the	O
+60S	O
+ribosomal	O
+subunit	O
+(	O
+3	O
+)	O
+.	O
+
+During	O
+the	O
+course	O
+of	O
+rRNA	O
+modification	O
+and	O
+processing	O
+,	O
+many	O
+of	O
+the	O
+ribosomal	O
+proteins	O
+are	O
+assembled	O
+onto	O
+the	O
+rRNA	O
+molecules	O
+to	O
+form	O
+the	O
+ribosome	O
+complex	O
+.	O
+
+Ribosome	O
+biogenesis	O
+needs	O
+a	O
+large	O
+number	O
+of	O
+trans	O
+-	O
+acting	O
+factors	O
+,	O
+including	O
+small	O
+nucleolar	O
+RNAs	O
+(	O
+snoRNAs	O
+)	O
+,	O
+protein	O
+components	O
+of	O
+the	O
+snoRNP	O
+complexes	O
+,	O
+rRNA	O
+modifying	O
+enzymes	O
+,	O
+endo	O
+-	O
+and	O
+exonucleases	O
+,	O
+putative	O
+RNA	O
+helicases	O
+and	O
+other	O
+protein	O
+factors	O
+(	O
+3	O
+,	O
+4	O
+)	O
+.	O
+
+In	O
+yeast	B
+cells	O
+there	O
+are	O
+more	O
+than	O
+100	O
+different	O
+snoRNAs	O
+playing	O
+important	O
+roles	O
+in	O
+rRNA	O
+modification	O
+and	O
+processing	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+their	O
+structure	O
+,	O
+the	O
+snoRNAs	O
+can	O
+be	O
+divided	O
+into	O
+two	O
+groups	O
+:	O
+the	O
+box	O
+C	O
+/	O
+D	O
+family	O
+and	O
+box	O
+H	O
+/	O
+ACA	O
+family	O
+.	O
+
+Only	O
+one	O
+snoRNA	O
+,	O
+MRP	O
+RNA	O
+,	O
+belongs	O
+to	O
+neither	O
+family	O
+(	O
+5	O
+-	O
+7	O
+)	O
+.	O
+
+While	O
+the	O
+majority	O
+of	O
+the	O
+snoRNAs	O
+participate	O
+in	O
+RNA	O
+pseudouridylation	O
+and	O
+2	O
+'	O
+-	O
+O	O
+-	O
+ribose	O
+methylation	O
+,	O
+a	O
+few	O
+of	O
+them	O
+,	O
+including	O
+MRP	O
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+,	O
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+C	O
+/	O
+D	O
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+and	O
+U14	O
+,	O
+and	O
+box	O
+H	O
+/	O
+ACA	O
+snoRNAs	O
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+snR30	O
+,	O
+are	O
+required	O
+for	O
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+of	O
+the	O
+pre	O
+-	O
+rRNA	O
+(	O
+8	O
+-	O
+12	O
+)	O
+.	O
+
+Not	O
+only	O
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+,	O
+U14	O
+,	O
+snR10	O
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+cleavages	O
+of	O
+35S	O
+pre	O
+-	O
+rRNA	O
+to	O
+18S	O
+rRNA	O
+,	O
+the	O
+proteins	O
+associated	O
+with	O
+them	O
+,	O
+including	O
+Nop1	O
+,	O
+Nop5	O
+,	O
+Gar1	O
+and	O
+Nop10	O
+,	O
+have	O
+also	O
+been	O
+shown	O
+to	O
+be	O
+required	O
+for	O
+18S	O
+rRNA	O
+synthesis	O
+(	O
+13	O
+-	O
+16	O
+)	O
+.	O
+
+The	O
+ENP1	O
+(	O
+Essential	O
+Nuclear	O
+Protein	O
+1	O
+)	O
+gene	O
+was	O
+identified	O
+in	O
+a	O
+genetic	O
+screen	O
+for	O
+suppressors	O
+of	O
+an	O
+ost4	O
+mutation	O
+(	O
+oligosaccharide	O
+transferase	O
+4	O
+)	O
+(	O
+17	O
+)	O
+.	O
+
+However	O
+,	O
+in	O
+subsequent	O
+studies	O
+it	O
+was	O
+found	O
+not	O
+to	O
+be	O
+involved	O
+in	O
+OST4	O
+function	O
+(	O
+18	O
+)	O
+.	O
+
+ENP1	O
+is	O
+an	O
+essential	O
+gene	O
+encoding	O
+a	O
+483	O
+amino	O
+acid	O
+polypeptide	O
+.	O
+
+The	O
+Enp1	O
+protein	O
+is	O
+highly	O
+conserved	O
+and	O
+homologs	O
+are	O
+found	O
+in	O
+all	O
+eukaryotes	O
+.	O
+
+The	O
+yeast	B
+protein	O
+was	O
+localized	O
+to	O
+the	O
+nucleus	O
+in	O
+a	O
+previous	O
+study	O
+(	O
+18	O
+)	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+an	O
+Enp1	O
+human	B
+homolog	O
+,	O
+called	O
+bystin	O
+,	O
+was	O
+reported	O
+to	O
+localize	O
+to	O
+the	O
+cytoplasm	O
+and	O
+was	O
+proposed	O
+to	O
+be	O
+involved	O
+in	O
+cell	O
+adhesion	O
+(	O
+19	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+report	O
+that	O
+the	O
+Enp1	O
+protein	O
+not	O
+only	O
+is	O
+nuclear	O
+but	O
+is	O
+enriched	O
+in	O
+the	O
+nucleolus	O
+.	O
+
+We	O
+also	O
+found	O
+that	O
+Enp1	O
+is	O
+required	O
+for	O
+the	O
+synthesis	O
+of	O
+40S	O
+ribosomal	O
+subunits	O
+,	O
+and	O
+its	O
+presence	O
+is	O
+necessary	O
+for	O
+the	O
+pre	O
+-	O
+rRNA	O
+processing	O
+to	O
+form	O
+20S	O
+pre	O
+-	O
+rRNA	O
+and	O
+18S	O
+rRNA	O
+.	O
+
+An	O
+association	O
+between	O
+Enp1	O
+and	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+,	O
+and	O
+with	O
+the	O
+nucleolar	O
+protein	O
+Nop1	O
+,	O
+was	O
+established	O
+.	O
+
+We	O
+also	O
+found	O
+that	O
+human	B
+Enp1	O
+,	O
+expressed	O
+in	O
+yeast	B
+,	O
+was	O
+located	O
+in	O
+the	O
+nucleus	O
+and	O
+the	O
+nucleolus	O
+,	O
+suggesting	O
+that	O
+the	O
+function	O
+of	O
+this	O
+protein	O
+is	O
+conserved	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+
+Yeast	B
+strains	O
+and	O
+media	O
+
+The	O
+S	B
+.	I
+cerevisiae	I
+strains	O
+used	O
+in	O
+this	O
+study	O
+are	O
+all	O
+derivatives	O
+of	O
+a	O
+wild	O
+-	O
+type	O
+diploid	O
+strain	O
+W303	O
+(	O
+MATa	O
+/	O
+MAT	O
+alpha	O
+ura3	O
+-	O
+1	O
+/	O
+ura3	O
+-	O
+1	O
+leu2	O
+-	O
+3	O
+,	O
+112	O
+/	O
+leu2	O
+-	O
+3	O
+,	O
+112	O
+trp1	O
+-	O
+1	O
+/	O
+trp1	O
+-	O
+1	O
+his3	O
+-	O
+11	O
+,	O
+15	O
+/	O
+his3	O
+-	O
+11	O
+,	O
+15	O
+ade2	O
+-	O
+1	O
+/	O
+ade2	O
+-	O
+1	O
+can1	O
+-	O
+100	O
+/	O
+can1	O
+-	O
+100	O
+)	O
+except	O
+for	O
+strain	O
+RS1938	O
+.	O
+
+Strain	O
+JBY45	O
+(	O
+MATa	O
+/	O
+MAT	O
+alpha	O
+ENP1	O
+/	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+)	O
+was	O
+constructed	O
+by	O
+replacing	O
+one	O
+copy	O
+of	O
+the	O
+ENP1	O
+open	O
+reading	O
+frame	O
+(	O
+ORF	O
+)	O
+with	O
+the	O
+Schizosaccharomyces	B
+pombe	I
+his5	O
++	O
+gene	O
+(	O
+18	O
+)	O
+.	O
+
+Strain	O
+JBY46	O
+[	O
+MATa	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+/	O
+pJB23	O
+(	O
+ENP1	O
+,	O
+URA3	O
+,	O
+CEN6	O
+)	O
+]	O
+is	O
+a	O
+haploid	O
+strain	O
+derived	O
+from	O
+JBY45	O
+with	O
+wild	O
+-	O
+type	O
+ENP1	O
+on	O
+a	O
+low	O
+copy	O
+number	O
+plasmid	O
+.	O
+
+Strain	O
+JBY48	O
+[	O
+MATa	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+/	O
+pJB19	O
+(	O
+enp1	O
+-	O
+1	O
+,	O
+TRP1	O
+,	O
+CEN6	O
+)	O
+]	O
+and	O
+strain	O
+JBY49	O
+[	O
+MATa	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+/	O
+pJB39	O
+(	O
+enp1	O
+-	O
+2	O
+,	O
+TRP1	O
+,	O
+CEN6	O
+)	O
+]	O
+have	O
+plasmids	O
+with	O
+enp1	O
+temperature	O
+-	O
+sensitive	O
+(	O
+ts	O
+)	O
+mutations	O
+.	O
+
+Strain	O
+JBY51	O
+(	O
+MATa	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+TRP1	O
+:	O
+:	O
+enp1	O
+-	O
+1	O
+)	O
+is	O
+an	O
+enp1	O
+ts	O
+strain	O
+generated	O
+by	O
+integrating	O
+the	O
+enp1	O
+-	O
+1	O
+gene	O
+at	O
+the	O
+chromosomal	O
+trp1	O
+-	O
+1	O
+locus	O
+.	O
+
+Strain	O
+CWY13	O
+[	O
+MATa	O
+Delta	O
+enp1	O
+:	O
+:	O
+his5	O
++	O
+/	O
+pJB24	O
+(	O
+pMET25	O
+-	O
+GFP	O
+-	O
+ENP1	O
+,	O
+URA3	O
+,	O
+CEN6	O
+)	O
+]	O
+has	O
+GFP	O
+-	O
+ENP1	O
+under	O
+control	O
+of	O
+the	O
+MET25	O
+promoter	O
+.	O
+
+Strain	O
+CWY14	O
+(	O
+MATa	O
+ENP1	O
+-	O
+TAP	O
+)	O
+was	O
+created	O
+by	O
+fusing	O
+sequences	O
+encoding	O
+a	O
+Tandem	O
+Affinity	O
+Purification	O
+(	O
+TAP	O
+)	O
+tag	O
+(	O
+20	O
+,	O
+21	O
+)	O
+to	O
+the	O
+3	O
+'	O
+end	O
+of	O
+ENP1	O
+.	O
+
+Strain	O
+YRH39	O
+(	O
+MAT	O
+alpha	O
+HST2	O
+-	O
+TAP	O
+)	O
+was	O
+created	O
+by	O
+fusing	O
+sequences	O
+encoding	O
+a	O
+TAP	O
+tag	O
+to	O
+the	O
+3	O
+'	O
+end	O
+of	O
+HST2	O
+.	O
+
+Strain	O
+RS1938	O
+(	O
+Delta	O
+nop1	O
+:	O
+:	O
+URA3	O
+pUN100	O
+-	O
+ProtA	O
+-	O
+NOP1	O
+)	O
+was	O
+created	O
+by	O
+transforming	O
+RS1935	O
+(	O
+MATa	O
+/	O
+alpha	O
+leu2	O
+/	O
+leu2	O
+ura3	O
+/	O
+ura3	O
+lys2	O
+/	O
+lys2	O
+ade2	O
+/	O
+ade2	O
+Delta	O
+nop1	O
+:	O
+:	O
+URA3	O
+/	O
+NOP1	O
+)	O
+with	O
+pUN100	O
+-	O
+ProtA	O
+-	O
+NOP1	O
+(	O
+strain	O
+and	O
+plasmid	O
+supplied	O
+by	O
+T	O
+.	O
+Schafer	O
+)	O
+,	O
+followed	O
+by	O
+tetrad	O
+dissection	O
+.	O
+
+Strain	O
+CWY15	O
+[	O
+MATa	O
+/	O
+pCW109	O
+(	O
+pMET25	O
+-	O
+GFP	O
+-	O
+hENP1	O
+,	O
+URA3	O
+,	O
+CEN6	O
+)	O
+]	O
+has	O
+a	O
+human	B
+homolog	O
+of	O
+Enp1	O
+expressed	O
+in	O
+W303	O
+-	O
+1a	O
+.	O
+
+The	O
+media	O
+used	O
+were	O
+prepared	O
+as	O
+described	O
+(	O
+22	O
+)	O
+.	O
+
+Cloning	O
+of	O
+ENP1	O
+
+pRS426	O
+-	O
+MEG1	O
+(	O
+The	O
+original	O
+name	O
+of	O
+ENP1	O
+)	O
+was	O
+a	O
+gift	O
+from	O
+Dr	O
+William	O
+J	O
+.	O
+Lennarz	O
+.	O
+
+It	O
+contains	O
+the	O
+ENP1	O
+gene	O
+within	O
+a	O
+2	O
+.	O
+6	O
+kb	O
+EcoRI	O
+genomic	O
+fragment	O
+cloned	O
+into	O
+pRS426	O
+(	O
+18	O
+)	O
+.	O
+
+The	O
+EcoRI	O
+fragment	O
+was	O
+subsequently	O
+cloned	O
+into	O
+pRS314	O
+(	O
+TRP1	O
+,	O
+CEN6	O
+)	O
+,	O
+pRS316	O
+(	O
+URA3	O
+,	O
+CEN6	O
+)	O
+and	O
+pRS424	O
+(	O
+TRP1	O
+,	O
+2	O
+micro	O
+)	O
+to	O
+create	O
+pJB20	O
+,	O
+pJB23	O
+and	O
+pJB21	O
+,	O
+respectively	O
+.	O
+
+pGFP	O
+-	O
+N	O
+-	O
+FUS	O
+is	O
+a	O
+centromeric	O
+plasmid	O
+for	O
+fusing	O
+green	O
+fluorescence	O
+protein	O
+(	O
+GFP	O
+)	O
+to	O
+a	O
+polypeptide	O
+'	O
+s	O
+N	O
+-	O
+terminus	O
+under	O
+control	O
+of	O
+the	O
+MET25	O
+promoter	O
+(	O
+23	O
+)	O
+.	O
+
+Cloning	O
+the	O
+ENP1	O
+ORF	O
+into	O
+pGFP	O
+-	O
+N	O
+-	O
+FUS	O
+via	O
+XbaI	O
+and	O
+SalI	O
+sites	O
+generated	O
+plasmid	O
+pJB24	O
+.	O
+
+pJB19	O
+(	O
+enp1	O
+-	O
+1	O
+,	O
+TRP1	O
+,	O
+CEN6	O
+)	O
+contains	O
+the	O
+enp1	O
+-	O
+1	O
+mutant	O
+gene	O
+.	O
+
+The	O
+human	B
+homolog	O
+of	O
+yeast	B
+Enp1	O
+was	O
+PCR	O
+amplified	O
+from	O
+a	O
+human	B
+cDNA	O
+clone	O
+BC007340	O
+(	O
+Research	O
+Genetics	O
+)	O
+,	O
+then	O
+cloned	O
+into	O
+pGFP	O
+-	O
+N	O
+-	O
+FUS	O
+,	O
+p415	O
+-	O
+ADH	O
+,	O
+p415	O
+-	O
+GPD	O
+and	O
+p415	O
+-	O
+TEF	O
+(	O
+24	O
+)	O
+via	O
+XbaI	O
+and	O
+SalI	O
+sites	O
+to	O
+generate	O
+pCW109	O
+,	O
+pCW113	O
+,	O
+pCW115	O
+and	O
+pCW117	O
+,	O
+respectively	O
+.	O
+
+The	O
+fragment	O
+of	O
+the	O
+human	B
+Enp1	O
+homolog	O
+(	O
+amino	O
+acids	O
+152	O
+-	O
+437	O
+)	O
+was	O
+also	O
+cloned	O
+into	O
+these	O
+vectors	O
+to	O
+generate	O
+pCW110	O
+,	O
+pCW114	O
+,	O
+pCW116	O
+and	O
+pCW118	O
+.	O
+
+Random	O
+mutagenesis	O
+of	O
+ENP1	O
+to	O
+generate	O
+enp1	O
+ts	O
+mutants	O
+
+The	O
+enp1	O
+ts	O
+mutants	O
+were	O
+generated	O
+with	O
+a	O
+protocol	O
+introducing	O
+random	O
+mutations	O
+by	O
+PCR	O
+(	O
+25	O
+)	O
+.	O
+
+The	O
+PCR	O
+was	O
+performed	O
+with	O
+oligonucleotides	O
+ENP1	O
+-	O
+MUT5	O
+'	O
+(	O
+5	O
+'	O
+-	O
+GGTGGTGTCAGT	O
+AGGGGA	O
+-	O
+3	O
+'	O
+)	O
+,	O
+ENP1	O
+-	O
+MUT3	O
+'	O
+(	O
+5	O
+'	O
+-	O
+CAGTCTGCAATATA	O
+TGGAC	O
+-	O
+3	O
+'	O
+)	O
+and	O
+plasmid	O
+template	O
+pJB20	O
+(	O
+see	O
+above	O
+)	O
+.	O
+
+The	O
+nucleotide	O
+concentrations	O
+in	O
+the	O
+reaction	O
+were	O
+1	O
+mM	O
+each	O
+for	O
+dATP	O
+,	O
+dGTP	O
+,	O
+dCTP	O
+and	O
+dTTP	O
+.	O
+
+After	O
+strain	O
+JBY46	O
+was	O
+transformed	O
+with	O
+the	O
+PCR	O
+product	O
+and	O
+with	O
+pJB20	O
+gapped	O
+by	O
+NheI	O
+and	O
+NsiI	O
+,	O
+the	O
+transformants	O
+were	O
+replica	O
+-	O
+plated	O
+onto	O
+two	O
+plates	O
+containing	O
+5	O
+-	O
+FOA	O
+synthetic	O
+medium	O
+without	O
+tryptophan	O
+;	O
+one	O
+replica	O
+was	O
+incubated	O
+at	O
+23	O
+degrees	O
+C	O
+and	O
+the	O
+other	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+Colonies	O
+growing	O
+at	O
+23	O
+degrees	O
+C	O
+but	O
+not	O
+at	O
+37	O
+degrees	O
+C	O
+were	O
+picked	O
+as	O
+candidates	O
+.	O
+
+Since	O
+approximately	O
+10	O
+%	O
+of	O
+the	O
+colonies	O
+were	O
+inviable	O
+at	O
+both	O
+temperatures	O
+,	O
+we	O
+knew	O
+that	O
+10	O
+%	O
+of	O
+the	O
+ENP1	O
+PCR	O
+products	O
+lost	O
+their	O
+function	O
+after	O
+the	O
+PCR	O
+mutagenesis	O
+.	O
+
+This	O
+confirmed	O
+the	O
+effectiveness	O
+of	O
+the	O
+mutagenesis	O
+procedure	O
+.	O
+
+Two	O
+candidates	O
+showed	O
+good	O
+growth	O
+at	O
+23	O
+degrees	O
+C	O
+but	O
+no	O
+growth	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+They	O
+were	O
+named	O
+strains	O
+JBY48	O
+and	O
+JBY49	O
+and	O
+contained	O
+plasmids	O
+with	O
+the	O
+enp1	O
+-	O
+1	O
+and	O
+enp1	O
+-	O
+2	O
+mutations	O
+,	O
+respectively	O
+.	O
+
+The	O
+mutated	O
+enp1	O
+-	O
+1	O
+gene	O
+on	O
+pJB19	O
+was	O
+cloned	O
+into	O
+an	O
+integration	O
+vector	O
+,	O
+pRS304	O
+,	O
+as	O
+an	O
+EcoRI	O
+fragment	O
+.	O
+
+The	O
+plasmid	O
+was	O
+subsequently	O
+linearized	O
+with	O
+SnaBI	O
+within	O
+the	O
+TRP1	O
+marker	O
+and	O
+was	O
+integrated	O
+at	O
+the	O
+chromosomal	O
+trp1	O
+-	O
+1	O
+locus	O
+of	O
+strain	O
+JBY46	O
+.	O
+
+Selection	O
+on	O
+5	O
+-	O
+FOA	O
+was	O
+used	O
+to	O
+remove	O
+plasmid	O
+pJB23	O
+,	O
+creating	O
+strain	O
+JBY51	O
+.	O
+
+Sucrose	O
+gradient	O
+analysis	O
+
+Polyribosome	O
+preparation	O
+and	O
+analysis	O
+were	O
+carried	O
+out	O
+essentially	O
+as	O
+described	O
+(	O
+26	O
+)	O
+.	O
+
+Cells	O
+grown	O
+in	O
+YPD	O
+were	O
+collected	O
+at	O
+mid	O
+-	O
+log	O
+phase	O
+(	O
+OD600	O
+0	O
+.	O
+8	O
+-	O
+1	O
+.	O
+0	O
+)	O
+and	O
+were	O
+broken	O
+with	O
+glass	O
+beads	O
+.	O
+
+The	O
+lysate	O
+was	O
+frozen	O
+immediately	O
+in	O
+liquid	O
+N2	O
+and	O
+was	O
+stored	O
+at	O
+-	O
+80	O
+degrees	O
+C	O
+.	O
+
+Lysate	O
+(	O
+30	O
+U	O
+of	O
+absorbance	O
+at	O
+OD260	O
+)	O
+was	O
+layered	O
+over	O
+a	O
+7	O
+-	O
+47	O
+%	O
+(	O
+w	O
+/	O
+v	O
+)	O
+sucrose	O
+gradient	O
+,	O
+which	O
+was	O
+centrifuged	O
+at	O
+28	O
+000	O
+r	O
+.	O
+p	O
+.	O
+m	O
+.	O
+for	O
+5	O
+h	O
+at	O
+4	O
+degrees	O
+C	O
+in	O
+a	O
+SW28	O
+rotor	O
+and	O
+was	O
+analyzed	O
+with	O
+an	O
+ISCO	O
+UA	O
+-	O
+5	O
+gradient	O
+UV	O
+detection	O
+system	O
+on	O
+absorbency	O
+at	O
+254	O
+nm	O
+.	O
+
+Immunofluorescence	O
+
+Immunofluorescence	O
+analysis	O
+was	O
+carried	O
+out	O
+essentially	O
+as	O
+described	O
+(	O
+27	O
+)	O
+.	O
+
+Cells	O
+were	O
+fixed	O
+with	O
+3	O
+.	O
+7	O
+%	O
+formaldehyde	O
+at	O
+room	O
+temperature	O
+for	O
+1	O
+.	O
+5	O
+h	O
+.	O
+
+Antibodies	O
+included	O
+a	O
+mouse	B
+monoclonal	O
+anti	O
+-	O
+Nop1	O
+(	O
+a	O
+gift	O
+from	O
+John	O
+P	O
+.	O
+Aris	O
+,	O
+University	O
+of	O
+Florida	O
+,	O
+Gainesville	O
+,	O
+Florida	O
+)	O
+and	O
+a	O
+Texas	O
+-	O
+red	O
+-	O
+conjugated	O
+donkey	B
+-	O
+anti	O
+-	O
+mouse	B
+antibody	O
+(	O
+Jackson	O
+Lab	O
+)	O
+,	O
+both	O
+used	O
+at	O
+1	O
+:	O
+500	O
+dilution	O
+.	O
+
+Images	O
+were	O
+taken	O
+on	O
+a	O
+Zeiss	O
+Axioplan2	O
+microscope	O
+equipped	O
+with	O
+a	O
+Zeiss	O
+AxioCam	O
+camera	O
+.	O
+
+Pulse	O
+-	O
+chase	O
+labeling	O
+analysis	O
+of	O
+rRNA	O
+
+For	O
+[	O
+methyl	O
+-	O
+3H	O
+]	O
+methionine	O
+pulse	O
+-	O
+chase	O
+analysis	O
+,	O
+cells	O
+were	O
+grown	O
+in	O
+synthetic	O
+medium	O
+without	O
+methionine	O
+at	O
+room	O
+temperature	O
+or	O
+37	O
+degrees	O
+C	O
+for	O
+2	O
+h	O
+.	O
+
+When	O
+the	O
+OD600	O
+reached	O
+1	O
+.	O
+0	O
+,	O
+6	O
+ml	O
+of	O
+the	O
+culture	O
+were	O
+pulse	O
+-	O
+labeled	O
+with	O
+250	O
+micro	O
+Ci	O
+[	O
+methyl	O
+-	O
+3H	O
+]	O
+methionine	O
+(	O
+Amersham	O
+Pharmacia	O
+)	O
+for	O
+3	O
+min	O
+and	O
+chased	O
+with	O
+cold	O
+methionine	O
+(	O
+500	O
+micro	O
+g	O
+/	O
+ml	O
+)	O
+for	O
+2	O
+,	O
+4	O
+or	O
+12	O
+min	O
+.	O
+
+For	O
+each	O
+time	O
+point	O
+of	O
+the	O
+chase	O
+1	O
+.	O
+25	O
+ml	O
+of	O
+culture	O
+was	O
+mixed	O
+with	O
+ice	O
+and	O
+collected	O
+.	O
+
+The	O
+pellets	O
+were	O
+frozen	O
+immediately	O
+in	O
+liquid	O
+N2	O
+and	O
+stored	O
+at	O
+-	O
+80	O
+degrees	O
+C	O
+before	O
+total	O
+RNA	O
+was	O
+purified	O
+using	O
+a	O
+hot	O
+phenol	O
+method	O
+(	O
+28	O
+)	O
+.	O
+
+The	O
+RNAs	O
+were	O
+separated	O
+on	O
+a	O
+1	O
+.	O
+2	O
+%	O
+agarose	O
+formaldehyde	O
+gel	O
+and	O
+transferred	O
+onto	O
+Hybond	O
+-	O
+N	O
++	O
+nylon	O
+membranes	O
+(	O
+Amersham	O
+Pharmacia	O
+)	O
+.	O
+
+After	O
+being	O
+sprayed	O
+with	O
+EN3HANCE	O
+(	O
+Du	O
+Pont	O
+)	O
+,	O
+the	O
+membranes	O
+were	O
+exposed	O
+to	O
+film	O
+at	O
+-	O
+80	O
+degrees	O
+C	O
+(	O
+29	O
+)	O
+.	O
+
+Northern	O
+analysis	O
+
+Cells	O
+were	O
+grown	O
+inYPD	O
+at	O
+room	O
+temperature	O
+or	O
+37	O
+degrees	O
+C	O
+for	O
+2	O
+-	O
+4	O
+h	O
+.	O
+
+When	O
+the	O
+OD600	O
+reached	O
+1	O
+.	O
+0	O
+,	O
+10	O
+ml	O
+of	O
+cells	O
+were	O
+collected	O
+and	O
+frozen	O
+immediately	O
+.	O
+
+Total	O
+RNA	O
+was	O
+extracted	O
+as	O
+described	O
+(	O
+28	O
+)	O
+.	O
+
+Five	O
+micrograms	O
+of	O
+RNA	O
+were	O
+separated	O
+on	O
+1	O
+.	O
+2	O
+%	O
+agarose	O
+formaldehyde	O
+gels	O
+(	O
+for	O
+high	O
+molecular	O
+weight	O
+RNA	O
+)	O
+or	O
+on	O
+6	O
+%	O
+polyacrylamide	O
+7	O
+M	O
+urea	O
+denaturing	O
+gels	O
+(	O
+for	O
+low	O
+molecular	O
+weight	O
+RNA	O
+)	O
+for	O
+each	O
+sample	O
+.	O
+
+The	O
+RNA	O
+was	O
+then	O
+transferred	O
+to	O
+Zeta	O
+-	O
+Probe	O
+GT	O
+nylon	O
+membranes	O
+(	O
+Bio	O
+-	O
+Rad	O
+)	O
+.	O
+
+Probes	O
+for	O
+hybridyzation	O
+were	O
+specific	O
+oligonucleotides	O
+end	O
+-	O
+labeled	O
+using	O
+[	O
+gamma	O
+-	O
+32P	O
+]	O
+ATP	O
+.	O
+
+After	O
+hybridization	O
+and	O
+washes	O
+,	O
+membranes	O
+were	O
+exposed	O
+to	O
+phosphorimager	O
+screens	O
+or	O
+X	O
+-	O
+ray	O
+films	O
+(	O
+29	O
+)	O
+.	O
+
+Oligonucleotides	O
+specific	O
+for	O
+various	O
+regions	O
+of	O
+35S	O
+pre	O
+-	O
+rRNA	O
+are	O
+:	O
+1	O
+,	O
+GGTCTCTCTGCTGCCG	O
+GAAATG	O
+;	O
+3	O
+,	O
+AATGAGCCATTCGCAGTTTC	O
+;	O
+4	O
+,	O
+GCTCTCATGCTCTTGCCAAA	O
+;	O
+5	O
+,	O
+TGTTTGTTACCT	O
+CTGGGCCCCG	O
+;	O
+6	O
+,	O
+TCCAGTTACGAAAATTCTTG	O
+;	O
+7	O
+,	O
+CGTATCGCATTTCGCTGCGT	O
+;	O
+8	O
+,	O
+GTTCGCCTAGAC	O
+GCTCTCTCTTC	O
+;	O
+9	O
+,	O
+GCGAGATTCCCCTACCCAC	O
+.	O
+
+The	O
+regions	O
+complementary	O
+to	O
+these	O
+oligonucleotides	O
+are	O
+shown	O
+in	O
+Figure	O
+6A	O
+.	O
+
+The	O
+oligonucleotides	O
+probing	O
+box	O
+C	O
+/	O
+D	O
+snoRNAs	O
+are	O
+:	O
+U3	O
+,	O
+TTCGGTTTCTCACTCACTCT	O
+;	O
+U14	O
+,	O
+GGAACCAGTCTTTCATCACC	O
+.	O
+
+The	O
+oligonucleotides	O
+probing	O
+box	O
+H	O
+/	O
+ACA	O
+snoRNAs	O
+are	O
+:	O
+snoRNA10	O
+,	O
+CCTTG	O
+CAACGGTCCTCATCCGGG	O
+;	O
+snoRNA30	O
+,	O
+GTCCGAAGC	O
+GCCATCTAGATGA	O
+.	O
+
+RNA	O
+and	O
+protein	O
+precipitation	O
+analysis	O
+
+Cells	O
+were	O
+grown	O
+in	O
+YPD	O
+(	O
+1	O
+l	O
+)	O
+to	O
+OD600	O
+1	O
+.	O
+0	O
+,	O
+then	O
+collected	O
+,	O
+washed	O
+once	O
+in	O
+ice	O
+-	O
+cold	O
+PBS	O
+and	O
+broken	O
+using	O
+glass	O
+beads	O
+in	O
+10	O
+ml	O
+IPP150	O
+buffer	O
+(	O
+10	O
+mM	O
+Tris	O
+pH	O
+8	O
+.	O
+0	O
+,	O
+150	O
+mM	O
+NaCl	O
+and	O
+0	O
+.	O
+1	O
+%	O
+NP	O
+-	O
+40	O
+)	O
+with	O
+protease	O
+inhibitors	O
+.	O
+
+The	O
+lysates	O
+were	O
+mixed	O
+with	O
+200	O
+micro	O
+l	O
+IgG	O
+agarose	O
+beads	O
+for	O
+2	O
+h	O
+at	O
+4	O
+degrees	O
+C	O
+.	O
+
+After	O
+several	O
+washes	O
+with	O
+50	O
+ml	O
+IPP150	O
+buffer	O
+,	O
+the	O
+IgG	O
+beads	O
+were	O
+collected	O
+and	O
+the	O
+RNA	O
+associated	O
+with	O
+the	O
+beads	O
+extracted	O
+by	O
+the	O
+hot	O
+phenol	O
+method	O
+(	O
+28	O
+)	O
+.	O
+
+One	O
+-	O
+tenth	O
+of	O
+the	O
+precipitated	O
+RNA	O
+was	O
+then	O
+separated	O
+on	O
+6	O
+%	O
+polyacrylamide	O
+7	O
+M	O
+urea	O
+denaturing	O
+gels	O
+and	O
+electro	O
+-	O
+transferred	O
+to	O
+Zeta	O
+-	O
+Probe	O
+GT	O
+nylon	O
+membranes	O
+.	O
+
+They	O
+were	O
+probed	O
+with	O
+[	O
+gamma	O
+-	O
+32P	O
+]	O
+ATP	O
+labeled	O
+oligonucleotides	O
+.	O
+
+For	O
+the	O
+lanes	O
+showing	O
+total	O
+RNA	O
+,	O
+2	O
+micro	O
+g	O
+RNA	O
+prepared	O
+from	O
+exponentially	O
+growing	O
+cultures	O
+were	O
+loaded	O
+.	O
+
+For	O
+co	O
+-	O
+precipitation	O
+analysis	O
+of	O
+proteins	O
+,	O
+the	O
+IgG	O
+beads	O
+were	O
+resuspended	O
+in	O
+2	O
+x	O
+Laemmli	O
+sample	O
+buffer	O
+,	O
+boiled	O
+for	O
+5	O
+min	O
+and	O
+separated	O
+by	O
+SDS	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+.	O
+
+Approximately	O
+1	O
+%	O
+of	O
+the	O
+precipitate	O
+was	O
+loaded	O
+onto	O
+each	O
+lane	O
+.	O
+
+For	O
+the	O
+total	O
+protein	O
+,	O
+0	O
+.	O
+1	O
+%	O
+of	O
+the	O
+extract	O
+prior	O
+to	O
+precipitation	O
+was	O
+loaded	O
+onto	O
+each	O
+lane	O
+.	O
+
+Following	O
+electrophoresis	O
+,	O
+the	O
+proteins	O
+were	O
+transferred	O
+to	O
+nitrocellulose	O
+membranes	O
+and	O
+detected	O
+using	O
+anti	O
+-	O
+Nop1	O
+antibody	O
+at	O
+1	O
+:	O
+3000	O
+dilution	O
+(	O
+provided	O
+by	O
+J	O
+.	O
+Aris	O
+)	O
+and	O
+anti	O
+-	O
+L3	O
+antibody	O
+(	O
+provided	O
+by	O
+J	O
+.	O
+Warner	O
+)	O
+at	O
+1	O
+:	O
+3000	O
+dilution	O
+followed	O
+by	O
+peroxidase	O
+-	O
+conjugated	O
+anti	O
+-	O
+mouse	B
+secondary	O
+antibody	O
+at	O
+1	O
+:	O
+5000	O
+dilution	O
+.	O
+
+The	O
+antibody	O
+complexes	O
+were	O
+detected	O
+using	O
+ECL	O
+-	O
+Plus	O
+reagents	O
+(	O
+Amersham	O
+Pharmacia	O
+)	O
+as	O
+specified	O
+by	O
+the	O
+manufacturer	O
+.	O
+
+RESULTS	O
+
+Construction	O
+and	O
+analysis	O
+of	O
+ENP1	O
+temperature	O
+-	O
+sensitive	O
+alleles	O
+
+ENP1	O
+is	O
+an	O
+essential	O
+yeast	B
+gene	O
+conserved	O
+among	O
+eukaryotes	O
+(	O
+18	O
+)	O
+.	O
+
+To	O
+study	O
+its	O
+functions	O
+,	O
+we	O
+first	O
+created	O
+a	O
+diploid	O
+strain	O
+,	O
+JBY45	O
+,	O
+heterozygous	O
+for	O
+the	O
+Delta	O
+enp1	O
+mutation	O
+.	O
+
+Then	O
+two	O
+enp1	O
+ts	O
+mutant	O
+alleles	O
+(	O
+enp1	O
+-	O
+1	O
+and	O
+enp1	O
+-	O
+2	O
+)	O
+were	O
+generated	O
+by	O
+random	O
+PCR	O
+mutagenesis	O
+,	O
+as	O
+described	O
+in	O
+Materials	O
+and	O
+Methods	O
+.	O
+
+Both	O
+mutant	O
+alleles	O
+were	O
+recessive	O
+to	O
+the	O
+wild	O
+-	O
+type	O
+ENP1	O
+gene	O
+.	O
+
+The	O
+enp1	O
+-	O
+1	O
+gene	O
+was	O
+integrated	O
+into	O
+the	O
+chromosomal	O
+trp1	O
+-	O
+1	O
+locus	O
+to	O
+create	O
+strain	O
+JBY51	O
+and	O
+all	O
+subsequent	O
+experiments	O
+were	O
+done	O
+with	O
+this	O
+enp1	O
+allele	O
+.	O
+
+At	O
+23	O
+degrees	O
+C	O
+the	O
+growth	O
+of	O
+JBY51	O
+was	O
+comparable	O
+to	O
+that	O
+of	O
+W303	O
+-	O
+1a	O
+(	O
+ENP1	O
+)	O
+,	O
+but	O
+at	O
+37	O
+degrees	O
+C	O
+it	O
+did	O
+not	O
+grow	O
+(	O
+Fig	O
+.	O
+2	O
+)	O
+.	O
+
+Sequence	O
+analysis	O
+revealed	O
+that	O
+enp1	O
+-	O
+1	O
+contains	O
+two	O
+point	O
+mutations	O
+,	O
+resulting	O
+in	O
+substitutions	O
+of	O
+two	O
+amino	O
+acids	O
+:	O
+W242	O
+-	O
+-	O
+>	O
+G	O
+and	O
+V415	O
+-	O
+-	O
+>	O
+A	O
+.	O
+
+No	O
+attempt	O
+was	O
+made	O
+to	O
+determine	O
+whether	O
+both	O
+mutations	O
+were	O
+required	O
+for	O
+the	O
+ts	O
+phenotype	O
+.	O
+
+Flow	O
+cytometry	O
+of	O
+strain	O
+JBY51	O
+showed	O
+DNA	O
+content	O
+profiles	O
+similar	O
+to	O
+those	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+strain	O
+at	O
+the	O
+non	O
+-	O
+permissive	O
+temperature	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+suggesting	O
+that	O
+ENP1	O
+is	O
+not	O
+involved	O
+in	O
+cell	O
+cycle	O
+regulation	O
+.	O
+
+Enp1	O
+is	O
+enriched	O
+in	O
+the	O
+nucleolus	O
+
+Enp1	O
+tagged	O
+at	O
+the	O
+C	O
+-	O
+terminus	O
+with	O
+the	O
+myc	O
+epitope	O
+was	O
+previously	O
+found	O
+to	O
+localize	O
+to	O
+the	O
+nucleus	O
+(	O
+18	O
+)	O
+.	O
+
+To	O
+expand	O
+this	O
+analysis	O
+,	O
+we	O
+fused	O
+GFP	O
+to	O
+the	O
+N	O
+-	O
+terminus	O
+of	O
+Enp1	O
+,	O
+and	O
+expressed	O
+the	O
+tagged	O
+Enp1	O
+protein	O
+under	O
+control	O
+of	O
+the	O
+MET25	O
+promoter	O
+as	O
+the	O
+sole	O
+source	O
+of	O
+Enp1	O
+protein	O
+in	O
+the	O
+cells	O
+.	O
+
+Cells	O
+of	O
+strain	O
+CWY13	O
+(	O
+pMET25	O
+-	O
+GFP	O
+-	O
+ENP1	O
+)	O
+were	O
+grown	O
+in	O
+media	O
+with	O
+methionine	O
+(	O
+transcription	O
+partially	O
+repressed	O
+)	O
+or	O
+without	O
+methionine	O
+(	O
+transcription	O
+not	O
+repressed	O
+)	O
+.	O
+
+Growth	O
+of	O
+CWY13	O
+was	O
+comparable	O
+to	O
+that	O
+of	O
+wild	O
+-	O
+type	O
+cells	O
+in	O
+both	O
+media	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+indicating	O
+that	O
+the	O
+GFP	O
+tagged	O
+Enp1	O
+protein	O
+was	O
+functional	O
+.	O
+
+In	O
+cells	O
+cultured	O
+in	O
+medium	O
+without	O
+methionine	O
+,	O
+in	O
+which	O
+the	O
+ENP	O
+transcription	O
+was	O
+not	O
+repressed	O
+,	O
+the	O
+GFP	O
+-	O
+Enp1	O
+protein	O
+was	O
+expressed	O
+at	O
+a	O
+high	O
+level	O
+and	O
+showed	O
+strong	O
+green	O
+fluorescence	O
+distributed	O
+throughout	O
+the	O
+nucleus	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+consistent	O
+with	O
+the	O
+original	O
+observation	O
+(	O
+18	O
+)	O
+.	O
+
+With	O
+methionine	O
+added	O
+to	O
+the	O
+medium	O
+,	O
+however	O
+,	O
+the	O
+fluorescent	O
+signal	O
+of	O
+GFP	O
+-	O
+Enp1	O
+was	O
+weaker	O
+and	O
+surprisingly	O
+showed	O
+crescent	O
+or	O
+cap	O
+-	O
+like	O
+patterns	O
+typical	O
+of	O
+nucleolar	O
+proteins	O
+(	O
+Fig	O
+.	O
+3A	O
+)	O
+.	O
+
+This	O
+nucleolar	O
+enrichment	O
+was	O
+confirmed	O
+by	O
+its	O
+co	O
+-	O
+localization	O
+with	O
+the	O
+nucleolar	O
+protein	O
+Nop1	O
+(	O
+Fig	O
+.	O
+3B	O
+)	O
+.	O
+
+ENP1	O
+mutation	O
+leads	O
+to	O
+reduced	O
+levels	O
+of	O
+40S	O
+ribosomal	O
+subunits	O
+
+The	O
+nucleolar	O
+enrichment	O
+suggested	O
+that	O
+Enp1	O
+might	O
+play	O
+some	O
+role	O
+in	O
+ribosome	O
+synthesis	O
+.	O
+
+To	O
+test	O
+this	O
+possibility	O
+,	O
+cells	O
+of	O
+W303	O
+-	O
+1a	O
+(	O
+ENP1	O
+)	O
+,	O
+JBY51	O
+(	O
+enp1	O
+-	O
+1	O
+)	O
+and	O
+a	O
+top2	O
+ts	O
+strain	O
+RS191	O
+(	O
+30	O
+)	O
+were	O
+grown	O
+in	O
+YPD	O
+at	O
+23	O
+or	O
+37	O
+degrees	O
+C	O
+and	O
+their	O
+ribosome	O
+profiles	O
+analyzed	O
+after	O
+separation	O
+on	O
+sucrose	O
+gradients	O
+.	O
+
+At	O
+23	O
+degrees	O
+C	O
+,	O
+enp1	O
+-	O
+1	O
+cells	O
+showed	O
+polysome	O
+profiles	O
+similar	O
+to	O
+those	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+and	O
+top2	O
+-	O
+1	O
+strains	O
+(	O
+Fig	O
+.	O
+4A	O
+-	O
+C	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+after	O
+incubation	O
+at	O
+the	O
+non	O
+-	O
+permissive	O
+temperature	O
+(	O
+37	O
+degrees	O
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+)	O
+for	O
+40	O
+min	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+and	O
+2	O
+h	O
+,	O
+enp1	O
+-	O
+1	O
+cells	O
+had	O
+reduced	O
+levels	O
+of	O
+40S	O
+ribosomal	O
+subunits	O
+,	O
+80S	O
+monosomes	O
+and	O
+polysomes	O
+,	O
+along	O
+with	O
+a	O
+dramatic	O
+increase	O
+in	O
+the	O
+free	O
+60S	O
+subunit	O
+peak	O
+(	O
+Fig	O
+.	O
+4F	O
+)	O
+,	O
+while	O
+the	O
+wild	O
+-	O
+type	O
+and	O
+top2	O
+-	O
+1	O
+cells	O
+showed	O
+little	O
+change	O
+in	O
+polysome	O
+profile	O
+at	O
+37	O
+degrees	O
+C	O
+(	O
+Fig	O
+.	O
+4D	O
+and	O
+E	O
+)	O
+.	O
+
+These	O
+results	O
+demonstrate	O
+that	O
+the	O
+changes	O
+of	O
+the	O
+enp1	O
+-	O
+1	O
+polysome	O
+profile	O
+were	O
+due	O
+to	O
+specific	O
+defects	O
+caused	O
+by	O
+the	O
+enp1	O
+-	O
+1	O
+mutation	O
+,	O
+and	O
+not	O
+due	O
+simply	O
+to	O
+the	O
+shift	O
+to	O
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+degrees	O
+C	O
+for	O
+a	O
+wild	O
+-	O
+type	O
+or	O
+ts	O
+strain	O
+.	O
+
+The	O
+processing	O
+of	O
+pre	O
+-	O
+rRNA	O
+for	O
+18S	O
+rRNA	O
+is	O
+impaired	O
+in	O
+enp1	O
+mutants	O
+
+In	O
+most	O
+cases	O
+reductions	O
+in	O
+ribosomal	O
+subunit	O
+levels	O
+are	O
+the	O
+results	O
+of	O
+defects	O
+in	O
+pre	O
+-	O
+rRNA	O
+processing	O
+or	O
+ribosome	O
+assembly	O
+or	O
+both	O
+(	O
+3	O
+)	O
+.	O
+
+To	O
+study	O
+the	O
+mechanism	O
+by	O
+which	O
+Enp1	O
+affects	O
+the	O
+40S	O
+subunit	O
+,	O
+we	O
+analyzed	O
+the	O
+effects	O
+of	O
+enp1	O
+mutations	O
+on	O
+processing	O
+of	O
+the	O
+pre	O
+-	O
+rRNA	O
+using	O
+pulse	O
+-	O
+chase	O
+labeling	O
+.	O
+
+[	O
+methyl	O
+-	O
+3H	O
+]	O
+methionine	O
+is	O
+preferred	O
+for	O
+labeling	O
+rRNAs	O
+in	O
+pulse	O
+-	O
+chase	O
+analysis	O
+because	O
+rRNAs	O
+are	O
+specifically	O
+methylated	O
+during	O
+the	O
+early	O
+steps	O
+of	O
+the	O
+processing	O
+.	O
+
+Cells	O
+of	O
+W303	O
+-	O
+1a	O
+(	O
+ENP1	O
+)	O
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+JBY51	O
+(	O
+enp1	O
+-	O
+1	O
+)	O
+were	O
+grown	O
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+23	O
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+degrees	O
+C	O
+for	O
+2	O
+h	O
+before	O
+they	O
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+labeled	O
+with	O
+[	O
+methyl	O
+-	O
+3H	O
+]	O
+methionine	O
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+3	O
+min	O
+and	O
+chased	O
+with	O
+cold	O
+methionine	O
+for	O
+2	O
+,	O
+4	O
+and	O
+12	O
+min	O
+.	O
+
+In	O
+wild	O
+-	O
+type	O
+cells	O
+,	O
+the	O
+labeled	O
+35S	O
+rRNA	O
+precursor	O
+,	O
+27S	O
+and	O
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+rRNA	O
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+were	O
+rapidly	O
+chased	O
+into	O
+mature	O
+25S	O
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+rRNAs	O
+(	O
+Fig	O
+.	O
+5	O
+)	O
+,	O
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+degrees	O
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+.	O
+
+In	O
+contrast	O
+,	O
+enp1	O
+-	O
+1	O
+cells	O
+showed	O
+dramatic	O
+changes	O
+after	O
+incubation	O
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+degrees	O
+C	O
+.	O
+
+Although	O
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+-	O
+type	O
+cells	O
+,	O
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+-	O
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+,	O
+while	O
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+generated	O
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+normal	O
+levels	O
+.	O
+
+The	O
+37	O
+degrees	O
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+grown	O
+enp1	O
+-	O
+1	O
+cells	O
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+had	O
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+levels	O
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+possibly	O
+21S	O
+intermediates	O
+(	O
+Fig	O
+.	O
+5	O
+)	O
+.	O
+
+The	O
+defect	O
+in	O
+18S	O
+rRNA	O
+synthesis	O
+was	O
+further	O
+supported	O
+by	O
+pulse	O
+-	O
+chase	O
+experiments	O
+carried	O
+out	O
+using	O
+[	O
+5	O
+,	O
+6	O
+-	O
+3H	O
+]	O
+uracil	O
+.	O
+
+The	O
+results	O
+obtained	O
+were	O
+essentially	O
+the	O
+same	O
+;	O
+no	O
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+pre	O
+-	O
+rRNA	O
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+produced	O
+,	O
+while	O
+processing	O
+to	O
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+was	O
+not	O
+affected	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+results	O
+suggested	O
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+the	O
+enp1	O
+mutation	O
+leads	O
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+defects	O
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+the	O
+processing	O
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+for	O
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+-	O
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+,	O
+resulting	O
+in	O
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+a	O
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+level	O
+of	O
+the	O
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+.	O
+
+Enp1	O
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+-	O
+rRNA	O
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+A0	O
+,	O
+A1	O
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+
+To	O
+define	O
+the	O
+processing	O
+steps	O
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+by	O
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+enp1	O
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+,	O
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+steady	O
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+analyzed	O
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+northern	O
+blotting	O
+.	O
+
+Total	O
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+isolated	O
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+cells	O
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+-	O
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+(	O
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+)	O
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+(	O
+enp1	O
+-	O
+1	O
+)	O
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+degrees	O
+C	O
+for	O
+2	O
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+4	O
+h	O
+.	O
+
+After	O
+separation	O
+on	O
+formaldehyde	O
+agarose	O
+,	O
+RNAs	O
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+transferred	O
+onto	O
+nylon	O
+membranes	O
+and	O
+probed	O
+with	O
+radiolabeled	O
+oligonucleotides	O
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+various	O
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+-	O
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+(	O
+Fig	O
+.	O
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+)	O
+.	O
+
+After	O
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+,	O
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+-	O
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+-	O
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+,	O
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+)	O
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+
+A	O
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+(	O
+P5	O
+)	O
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+-	O
+1	O
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+-	O
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+,	O
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+(	O
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+.	O
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+)	O
+.	O
+
+Aberrant	O
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+products	O
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+similar	O
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+have	O
+been	O
+described	O
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+numerous	O
+studies	O
+(	O
+14	O
+,	O
+31	O
+-	O
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+)	O
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+,	O
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+.	O
+
+Additional	O
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+-	O
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+.	O
+
+The	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+)	O
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+
+Thus	O
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+
+The	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+)	O
+,	O
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+.	O
+
+At	O
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+-	O
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+(	O
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+.	O
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+)	O
+.	O
+
+These	O
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+,	O
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+
+As	O
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+,	O
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+-	O
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+,	O
+producing	O
+23S	O
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+rRNA	O
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+.	O
+
+Consistent	O
+with	O
+this	O
+theory	O
+,	O
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+(	O
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+.	O
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+)	O
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+,	O
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+-	O
+rRNA	O
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+wild	O
+-	O
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+(	O
+Fig	O
+.	O
+6G	O
+)	O
+.	O
+
+Moreover	O
+,	O
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+difference	O
+in	O
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+.	O
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+observed	O
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+wild	O
+-	O
+type	O
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+(	O
+Fig	O
+.	O
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+)	O
+.	O
+
+Enp1	O
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+U14	O
+snoRNAs	O
+and	O
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+Nop1	O
+
+It	O
+has	O
+previously	O
+been	O
+shown	O
+that	O
+mutations	O
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+the	O
+U3	O
+,	O
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+,	O
+snR10	O
+and	O
+snR30	O
+snoRNAs	O
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+in	O
+their	O
+associated	O
+proteins	O
+affect	O
+processing	O
+of	O
+35S	O
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+-	O
+rRNA	O
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+A0	O
+,	O
+A1	O
+and	O
+A2	O
+.	O
+
+Because	O
+of	O
+the	O
+similarity	O
+with	O
+the	O
+processing	O
+defects	O
+of	O
+enp1	O
+-	O
+1	O
+strains	O
+,	O
+we	O
+tested	O
+the	O
+association	O
+between	O
+Enp1	O
+and	O
+snoRNAs	O
+.	O
+
+To	O
+do	O
+this	O
+,	O
+we	O
+created	O
+a	O
+strain	O
+in	O
+which	O
+a	O
+TAP	O
+tag	O
+was	O
+fused	O
+to	O
+the	O
+C	O
+-	O
+terminus	O
+of	O
+Enp1	O
+.	O
+
+The	O
+TAP	O
+tag	O
+contains	O
+Staphylococcus	B
+aureus	I
+Protein	O
+A	O
+as	O
+well	O
+as	O
+calmodulin	O
+-	O
+binding	O
+peptide	O
+sequences	O
+,	O
+so	O
+the	O
+tagged	O
+Enp1	O
+binds	O
+IgG	O
+beads	O
+with	O
+high	O
+specificity	O
+.	O
+
+Cells	O
+grew	O
+well	O
+with	O
+the	O
+TAP	O
+-	O
+tagged	O
+Enp1	O
+as	O
+the	O
+only	O
+source	O
+of	O
+Enp1	O
+protein	O
+,	O
+showing	O
+that	O
+it	O
+was	O
+functional	O
+.	O
+
+As	O
+a	O
+control	O
+,	O
+we	O
+used	O
+a	O
+TAP	O
+tag	O
+on	O
+an	O
+unrelated	O
+cytoplasmic	O
+protein	O
+,	O
+Hst2	O
+.	O
+
+Strain	O
+CWY14	O
+(	O
+ENP1	O
+-	O
+TAP	O
+)	O
+and	O
+the	O
+Hst2	O
+-	O
+TAP	O
+tagged	O
+strain	O
+were	O
+grown	O
+in	O
+YPD	O
+to	O
+mid	O
+-	O
+exponential	O
+phase	O
+before	O
+being	O
+harvested	O
+.	O
+
+Extracts	O
+were	O
+prepared	O
+and	O
+mixed	O
+with	O
+IgG	O
+agarose	O
+beads	O
+to	O
+precipitate	O
+Enp1	O
+-	O
+TAP	O
+and	O
+associated	O
+RNAs	O
+.	O
+
+Total	O
+RNAs	O
+were	O
+extracted	O
+from	O
+washed	O
+IgG	O
+beads	O
+,	O
+separated	O
+on	O
+6	O
+%	O
+polyacrylamide	O
+denaturing	O
+gels	O
+,	O
+transferred	O
+to	O
+nylon	O
+membranes	O
+and	O
+probed	O
+with	O
+radiolabeled	O
+oligonucleotides	O
+.	O
+
+Northern	O
+analysis	O
+revealed	O
+that	O
+Enp1	O
+-	O
+TAP	O
+precipitates	O
+were	O
+enriched	O
+with	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+relative	O
+to	O
+precipitates	O
+from	O
+the	O
+Hst2	O
+-	O
+tagged	O
+strain	O
+(	O
+Fig	O
+.	O
+7A	O
+)	O
+.	O
+
+The	O
+Enp1	O
+-	O
+TAP	O
+samples	O
+were	O
+not	O
+enriched	O
+with	O
+snR30	O
+snoRNA	O
+(	O
+Fig	O
+.	O
+7A	O
+)	O
+,	O
+nor	O
+with	O
+U24	O
+or	O
+U18	O
+snoRNAs	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+We	O
+found	O
+no	O
+change	O
+in	O
+the	O
+levels	O
+of	O
+U3	O
+,	O
+U14	O
+,	O
+snR10	O
+and	O
+snR30	O
+snoRNAs	O
+in	O
+the	O
+enp1	O
+mutant	O
+,	O
+indicating	O
+that	O
+the	O
+mutation	O
+did	O
+not	O
+affect	O
+snoRNAs	O
+levels	O
+(	O
+Fig	O
+.	O
+6I	O
+)	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+Enp1	O
+associates	O
+in	O
+vivo	O
+with	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+.	O
+
+Much	O
+less	O
+U3	O
+RNA	O
+co	O
+-	O
+immunoprecipitated	O
+with	O
+Enp1	O
+-	O
+TAP	O
+than	O
+with	O
+Protein	O
+A	O
+-	O
+tagged	O
+Nop1	O
+,	O
+which	O
+is	O
+known	O
+to	O
+associate	O
+with	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+(	O
+Fig	O
+.	O
+7A	O
+)	O
+.	O
+
+However	O
+,	O
+Protein	O
+A	O
+-	O
+Nop1	O
+was	O
+much	O
+more	O
+efficiently	O
+precipitated	O
+than	O
+was	O
+the	O
+Enp1	O
+-	O
+TAP	O
+protein	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+similar	O
+amounts	O
+of	O
+RNAs	O
+are	O
+associated	O
+with	O
+the	O
+two	O
+proteins	O
+and	O
+that	O
+the	O
+proteins	O
+are	O
+part	O
+of	O
+the	O
+same	O
+complex	O
+.	O
+
+To	O
+address	O
+this	O
+further	O
+,	O
+we	O
+checked	O
+for	O
+the	O
+presence	O
+of	O
+Nop1	O
+in	O
+the	O
+Enp1	O
+-	O
+TAP	O
+immunoprecipitates	O
+.	O
+
+Figure	O
+7B	O
+shows	O
+that	O
+Nop1	O
+indeed	O
+is	O
+in	O
+the	O
+Enp1	O
+precipitate	O
+but	O
+not	O
+in	O
+the	O
+Hst2	O
+control	O
+,	O
+whereas	O
+an	O
+abundant	O
+ribosomal	O
+protein	O
+,	O
+L3	O
+,	O
+is	O
+in	O
+neither	O
+precipitate	O
+.	O
+
+U3	O
+and	O
+U14	O
+snoRNAs	O
+have	O
+been	O
+shown	O
+to	O
+interact	O
+with	O
+rRNA	O
+precursors	O
+and	O
+these	O
+interactions	O
+are	O
+required	O
+for	O
+pre	O
+-	O
+rRNA	O
+processing	O
+(	O
+35	O
+-	O
+37	O
+)	O
+.	O
+
+Using	O
+an	O
+in	O
+vitro	O
+system	O
+,	O
+U3	O
+was	O
+also	O
+shown	O
+to	O
+be	O
+associated	O
+with	O
+its	O
+rRNA	O
+substrate	O
+and	O
+processing	O
+product	O
+(	O
+38	O
+)	O
+.	O
+
+This	O
+raised	O
+the	O
+possibility	O
+that	O
+Enp1	O
+might	O
+also	O
+be	O
+associated	O
+with	O
+rRNAs	O
+since	O
+its	O
+function	O
+in	O
+rRNA	O
+processing	O
+appeared	O
+linked	O
+to	O
+those	O
+of	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+.	O
+
+To	O
+test	O
+this	O
+possibility	O
+,	O
+we	O
+further	O
+analyzed	O
+the	O
+RNAs	O
+that	O
+co	O
+-	O
+precipiate	O
+with	O
+TAP	O
+-	O
+tagged	O
+Enp1	O
+.	O
+
+The	O
+RNAs	O
+were	O
+separated	O
+on	O
+1	O
+.	O
+2	O
+%	O
+agarose	O
+formaldehyde	O
+gels	O
+or	O
+on	O
+polyacrylamide	O
+denaturing	O
+gels	O
+,	O
+transferred	O
+to	O
+nylon	O
+membranes	O
+and	O
+probed	O
+with	O
+radiolabeled	O
+oligonucleotides	O
+for	O
+pre	O
+-	O
+rRNAs	O
+.	O
+
+A	O
+probe	O
+(	O
+P4	O
+;	O
+see	O
+Fig	O
+.	O
+6	O
+)	O
+specific	O
+to	O
+20s	O
+and	O
+its	O
+precursors	O
+revealed	O
+that	O
+pre	O
+-	O
+rRNAs	O
+35S	O
+,	O
+33S	O
+,	O
+32S	O
+and	O
+20S	O
+specifically	O
+co	O
+-	O
+precipitated	O
+with	O
+Enp1	O
+-	O
+TAP	O
+(	O
+Fig	O
+.	O
+7C	O
+)	O
+.	O
+
+No	O
+such	O
+enrichment	O
+was	O
+found	O
+using	O
+a	O
+probe	O
+(	O
+P8	O
+;	O
+see	O
+Fig	O
+.	O
+6	O
+)	O
+specific	O
+for	O
+27S	O
+RNAs	O
+or	O
+a	O
+probe	O
+for	O
+5	O
+.	O
+8S	O
+RNA	O
+(	O
+Fig	O
+.	O
+7C	O
+)	O
+.	O
+
+These	O
+results	O
+clearly	O
+demonstrated	O
+that	O
+Enp1	O
+is	O
+associated	O
+with	O
+substrates	O
+and	O
+products	O
+of	O
+the	O
+early	O
+steps	O
+of	O
+18S	O
+rRNA	O
+processing	O
+.	O
+
+Comparison	O
+of	O
+Enp1	O
+with	O
+homologs	O
+in	O
+other	O
+organisms	O
+
+Homologs	O
+of	O
+Enp1	O
+protein	O
+in	O
+human	B
+,	O
+Drosophila	B
+and	O
+Caenorhabditis	B
+elegans	I
+have	O
+been	O
+reported	O
+(	O
+18	O
+)	O
+.	O
+
+A	O
+previously	O
+described	O
+human	B
+homolog	O
+,	O
+bystin	O
+,	O
+was	O
+only	O
+306	O
+amino	O
+acids	O
+in	O
+length	O
+,	O
+and	O
+lacked	O
+sequences	O
+corresponding	O
+to	O
+the	O
+N	O
+-	O
+terminal	O
+163	O
+amino	O
+acids	O
+of	O
+yeast	B
+Enp1	O
+(	O
+19	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+we	O
+identified	O
+a	O
+human	B
+expressed	O
+sequence	O
+tag	O
+(	O
+EST	O
+)	O
+,	O
+BC007340	O
+in	O
+a	O
+Blast	O
+search	O
+that	O
+revealed	O
+an	O
+ORF	O
+of	O
+1311	O
+nucleotides	O
+encoding	O
+a	O
+437	O
+amino	O
+acid	O
+polypeptide	O
+(	O
+39	O
+)	O
+.	O
+
+Comparison	O
+of	O
+this	O
+437	O
+amino	O
+acid	O
+polypeptide	O
+with	O
+human	B
+bystin	O
+(	O
+19	O
+)	O
+showed	O
+that	O
+they	O
+were	O
+encoded	O
+by	O
+the	O
+same	O
+gene	O
+on	O
+human	B
+chromosome	O
+6	O
+.	O
+
+The	O
+reported	O
+sequence	O
+for	O
+human	B
+bystin	O
+is	O
+a	O
+fragment	O
+of	O
+the	O
+437	O
+amino	O
+acid	O
+human	B
+Enp1	O
+protein	O
+,	O
+due	O
+to	O
+a	O
+truncated	O
+cDNA	O
+sequence	O
+.	O
+
+Also	O
+,	O
+a	O
+sequence	O
+discrepancy	O
+at	O
+the	O
+C	O
+-	O
+terminus	O
+is	O
+due	O
+to	O
+inaccurate	O
+DNA	O
+sequence	O
+of	O
+the	O
+human	B
+bystin	O
+,	O
+as	O
+confirmed	O
+by	O
+available	O
+human	B
+genome	O
+and	O
+EST	O
+sequences	O
+.	O
+
+Searches	O
+of	O
+the	O
+database	O
+of	O
+other	O
+organisms	O
+identified	O
+Enp1	O
+homologs	O
+in	O
+S	B
+.	I
+pombe	I
+,	O
+Arabidopsis	B
+thaliana	I
+,	O
+C	B
+.	I
+elegans	I
+,	O
+Drosophila	B
+melanogaster	I
+and	O
+mouse	B
+.	O
+
+The	O
+alignment	O
+of	O
+the	O
+homologs	O
+showed	O
+that	O
+they	O
+shared	O
+homology	O
+from	O
+the	O
+N	O
+-	O
+terminus	O
+to	O
+the	O
+C	O
+-	O
+terminus	O
+,	O
+with	O
+the	O
+C	O
+-	O
+terminal	O
+half	O
+extremely	O
+well	O
+conserved	O
+,	O
+with	O
+close	O
+to	O
+90	O
+%	O
+similarity	O
+(	O
+Fig	O
+.	O
+8	O
+)	O
+.	O
+
+One	O
+interesting	O
+observation	O
+is	O
+that	O
+the	O
+two	O
+amino	O
+acids	O
+changed	O
+in	O
+the	O
+enp1	O
+-	O
+1	O
+mutant	O
+,	O
+W242	O
+and	O
+V415	O
+,	O
+are	O
+conserved	O
+among	O
+all	O
+homologs	O
+.	O
+
+The	O
+human	B
+Enp1	O
+homolog	O
+was	O
+cloned	O
+and	O
+expressed	O
+in	O
+yeast	B
+and	O
+tested	O
+for	O
+function	O
+.	O
+
+Expressed	O
+under	O
+the	O
+control	O
+of	O
+ADH	O
+,	O
+TEF	O
+or	O
+GPD	O
+promoter	O
+,	O
+the	O
+human	B
+Enp1	O
+homolog	O
+did	O
+not	O
+complement	O
+a	O
+yeast	B
+enp1	O
+null	O
+mutant	O
+.	O
+
+However	O
+,	O
+a	O
+GFP	O
+fusion	O
+to	O
+the	O
+N	O
+-	O
+terminus	O
+of	O
+human	B
+Enp1	O
+homolog	O
+localized	O
+to	O
+the	O
+nucleus	O
+and	O
+was	O
+enriched	O
+in	O
+the	O
+nucleolus	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+DISCUSSION	O
+
+ENP1	O
+is	O
+a	O
+yeast	B
+gene	O
+first	O
+identified	O
+in	O
+a	O
+genetic	O
+screen	O
+for	O
+complementation	O
+of	O
+mutations	O
+in	O
+ost4	O
+,	O
+which	O
+encodes	O
+a	O
+subunit	O
+of	O
+oligosaccharide	O
+transferase	O
+(	O
+17	O
+)	O
+,	O
+although	O
+subsequent	O
+work	O
+showed	O
+that	O
+it	O
+is	O
+unlikely	O
+that	O
+Enp1	O
+has	O
+any	O
+connection	O
+to	O
+oligosaccharide	O
+transferase	O
+(	O
+18	O
+)	O
+.	O
+
+ENP1	O
+was	O
+shown	O
+to	O
+be	O
+essential	O
+for	O
+viability	O
+and	O
+the	O
+Enp1	O
+protein	O
+localized	O
+to	O
+the	O
+nucleus	O
+(	O
+18	O
+)	O
+.	O
+
+When	O
+we	O
+re	O
+-	O
+examined	O
+the	O
+localization	O
+of	O
+Enp1	O
+,	O
+we	O
+observed	O
+that	O
+the	O
+protein	O
+was	O
+enriched	O
+in	O
+the	O
+nucleolus	O
+.	O
+
+This	O
+finding	O
+led	O
+us	O
+to	O
+test	O
+for	O
+a	O
+role	O
+of	O
+Enp1	O
+in	O
+ribosome	O
+synthesis	O
+.	O
+
+Using	O
+an	O
+enp1	O
+ts	O
+mutant	O
+,	O
+we	O
+found	O
+that	O
+depletion	O
+of	O
+Enp1	O
+caused	O
+a	O
+40S	O
+ribosomal	O
+subunit	O
+deficiency	O
+.	O
+
+Further	O
+analysis	O
+revealed	O
+that	O
+this	O
+deficiency	O
+was	O
+not	O
+due	O
+to	O
+a	O
+change	O
+of	O
+the	O
+subunit	O
+'	O
+s	O
+stability	O
+,	O
+but	O
+to	O
+a	O
+defect	O
+in	O
+the	O
+synthesis	O
+of	O
+the	O
+subunit	O
+'	O
+s	O
+18S	O
+rRNA	O
+component	O
+.	O
+
+Pulse	O
+-	O
+chase	O
+analysis	O
+of	O
+RNA	O
+synthesis	O
+in	O
+an	O
+enp1	O
+-	O
+1	O
+strain	O
+revealed	O
+that	O
+no	O
+20S	O
+pre	O
+-	O
+rRNA	O
+or	O
+18S	O
+rRNA	O
+was	O
+made	O
+at	O
+the	O
+non	O
+-	O
+permissive	O
+temperature	O
+,	O
+while	O
+levels	O
+of	O
+25S	O
+rRNA	O
+appeared	O
+normal	O
+.	O
+
+Low	O
+levels	O
+of	O
+precursors	O
+to	O
+18S	O
+rRNA	O
+were	O
+detected	O
+in	O
+the	O
+mutants	O
+,	O
+and	O
+they	O
+were	O
+extremely	O
+unstable	O
+.	O
+
+Northern	O
+analysis	O
+of	O
+steady	O
+state	O
+RNA	O
+levels	O
+demonstrated	O
+that	O
+the	O
+enp1	O
+mutation	O
+specifically	O
+inhibited	O
+the	O
+pre	O
+-	O
+rRNA	O
+early	O
+cleavages	O
+at	O
+sites	O
+A0	O
+,	O
+A1	O
+and	O
+A2	O
+,	O
+which	O
+are	O
+required	O
+for	O
+the	O
+production	O
+of	O
+the	O
+20S	O
+pre	O
+-	O
+rRNA	O
+and	O
+the	O
+18S	O
+rRNA	O
+.	O
+
+These	O
+defects	O
+of	O
+the	O
+enp1	O
+mutation	O
+on	O
+rRNA	O
+processing	O
+are	O
+very	O
+similar	O
+to	O
+those	O
+caused	O
+by	O
+mutation	O
+of	O
+KRR1	O
+,	O
+another	O
+essential	O
+nucleolar	O
+gene	O
+required	O
+for	O
+synthesis	O
+of	O
+the	O
+40S	O
+,	O
+but	O
+not	O
+the	O
+60S	O
+subunit	O
+(	O
+40	O
+)	O
+.	O
+
+Co	O
+-	O
+precipitation	O
+analyses	O
+provided	O
+strong	O
+evidence	O
+that	O
+Enp1	O
+is	O
+directly	O
+involved	O
+in	O
+pre	O
+-	O
+rRNA	O
+processing	O
+.	O
+
+In	O
+these	O
+experiments	O
+,	O
+TAP	O
+-	O
+tagged	O
+Enp1	O
+bound	O
+to	O
+IgG	O
+beads	O
+specifically	O
+co	O
+-	O
+precipitated	O
+with	O
+two	O
+snoRNAs	O
+,	O
+U3	O
+and	O
+U14	O
+,	O
+and	O
+with	O
+the	O
+35S	O
+,	O
+33S	O
+,	O
+32S	O
+and	O
+20S	O
+pre	O
+-	O
+rRNAs	O
+.	O
+
+Among	O
+the	O
+more	O
+than	O
+100	O
+snoRNAs	O
+in	O
+yeast	B
+cells	O
+,	O
+U3	O
+,	O
+U14	O
+,	O
+snR10	O
+,	O
+snR30	O
+and	O
+MRP	O
+RNA	O
+are	O
+the	O
+only	O
+ones	O
+required	O
+for	O
+rRNA	O
+processing	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+that	O
+mutations	O
+in	O
+U3	O
+,	O
+U14	O
+,	O
+snR10	O
+and	O
+snR30	O
+snoRNAs	O
+and	O
+protein	O
+components	O
+of	O
+the	O
+snoRNPs	O
+affect	O
+processing	O
+at	O
+sites	O
+A0	O
+,	O
+A1	O
+or	O
+A2	O
+(	O
+15	O
+,	O
+16	O
+,	O
+41	O
+,	O
+42	O
+)	O
+.	O
+
+Enp1	O
+'	O
+s	O
+interaction	O
+with	O
+U3	O
+and	O
+U14	O
+snoRNAs	O
+suggests	O
+that	O
+Enp1	O
+'	O
+s	O
+function	O
+in	O
+rRNA	O
+processing	O
+involves	O
+these	O
+two	O
+snoRNAs	O
+.	O
+
+The	O
+fact	O
+that	O
+the	O
+nucleolar	O
+protein	O
+,	O
+Nop1	O
+,	O
+known	O
+to	O
+bind	O
+to	O
+U3	O
+and	O
+U14	O
+RNAs	O
+,	O
+also	O
+was	O
+found	O
+in	O
+the	O
+Enp1	O
+precipitate	O
+,	O
+provides	O
+additional	O
+evidence	O
+that	O
+Enp1	O
+is	O
+part	O
+of	O
+a	O
+complex	O
+involved	O
+in	O
+processing	O
+of	O
+rRNA	O
+.	O
+
+Recently	O
+,	O
+a	O
+genome	O
+-	O
+wide	O
+study	O
+of	O
+yeast	B
+protein	O
+complexes	O
+,	O
+using	O
+a	O
+TAP	O
+tag	O
+method	O
+similar	O
+to	O
+ours	O
+,	O
+reported	O
+a	O
+number	O
+of	O
+proteins	O
+that	O
+co	O
+-	O
+immunoprecipitated	O
+with	O
+Enp1	O
+(	O
+43	O
+)	O
+.	O
+
+These	O
+proteins	O
+included	O
+Imp4	O
+,	O
+Kre31	O
+,	O
+Kre33	O
+,	O
+Mpp10	O
+,	O
+Nop1	O
+,	O
+Nop14	O
+and	O
+Sof1	O
+,	O
+all	O
+of	O
+which	O
+have	O
+been	O
+implicated	O
+in	O
+18S	O
+RNA	O
+processing	O
+or	O
+40S	O
+biogenesis	O
+.	O
+
+Very	O
+recently	O
+(	O
+after	O
+the	O
+studies	O
+in	O
+this	O
+manuscript	O
+were	O
+concluded	O
+)	O
+Grandi	O
+et	O
+al	O
+.	O
+published	O
+an	O
+analysis	O
+of	O
+components	O
+of	O
+the	O
+90s	O
+preribosomal	O
+particle	O
+,	O
+which	O
+include	O
+the	O
+35S	O
+pre	O
+-	O
+rRNA	O
+,	O
+U3	O
+snoRNP	O
+and	O
+rRNA	O
+processing	O
+factors	O
+for	O
+the	O
+40S	O
+subunit	O
+(	O
+44	O
+)	O
+.	O
+
+In	O
+agreement	O
+with	O
+our	O
+findings	O
+,	O
+they	O
+found	O
+that	O
+Enp1	O
+is	O
+a	O
+component	O
+of	O
+this	O
+90s	O
+complex	O
+and	O
+also	O
+of	O
+a	O
+smaller	O
+complex	O
+containing	O
+the	O
+20S	O
+pre	O
+-	O
+rRNA	O
+.	O
+
+Surprisingly	O
+,	O
+none	O
+of	O
+the	O
+other	O
+proteins	O
+involved	O
+in	O
+processing	O
+of	O
+pre	O
+-	O
+rRNAs	O
+that	O
+were	O
+tested	O
+associated	O
+with	O
+the	O
+20S	O
+rRNA	O
+,	O
+suggesting	O
+that	O
+those	O
+proteins	O
+,	O
+but	O
+not	O
+Enp1	O
+,	O
+are	O
+released	O
+prior	O
+to	O
+20S	O
+pre	O
+-	O
+rRNA	O
+formation	O
+(	O
+44	O
+)	O
+.	O
+
+The	O
+authors	O
+also	O
+showed	O
+co	O
+-	O
+precipitation	O
+of	O
+Enp1	O
+with	O
+dimethylated	O
+20S	O
+pre	O
+-	O
+rRNA	O
+,	O
+which	O
+is	O
+formed	O
+after	O
+export	O
+of	O
+20S	O
+to	O
+the	O
+cytoplasm	O
+.	O
+
+These	O
+results	O
+of	O
+Grandi	O
+et	O
+al	O
+.	O
+suggest	O
+that	O
+Enp1	O
+may	O
+also	O
+be	O
+involved	O
+in	O
+later	O
+steps	O
+of	O
+processing	O
+or	O
+nuclear	O
+export	O
+.	O
+
+A	O
+previous	O
+study	O
+on	O
+the	O
+Enp1	O
+human	B
+homolog	O
+,	O
+bystin	O
+,	O
+reported	O
+that	O
+the	O
+protein	O
+was	O
+localized	O
+in	O
+the	O
+cytoplasm	O
+of	O
+mammalian	O
+cells	O
+and	O
+might	O
+be	O
+involved	O
+in	O
+cell	O
+adhesion	O
+(	O
+19	O
+)	O
+.	O
+
+Our	O
+discovery	O
+of	O
+the	O
+437	O
+amino	O
+acid	O
+human	B
+Enp1	O
+homolog	O
+revealed	O
+that	O
+the	O
+bystin	O
+studied	O
+previously	O
+was	O
+from	O
+a	O
+truncated	O
+library	O
+cDNA	O
+encoding	O
+only	O
+the	O
+C	O
+-	O
+terminal	O
+306	O
+amino	O
+acids	O
+.	O
+
+Although	O
+the	O
+human	B
+homolog	O
+of	O
+Enp1	O
+did	O
+not	O
+complement	O
+a	O
+yeast	B
+Delta	O
+enp1	O
+mutant	O
+,	O
+we	O
+did	O
+show	O
+that	O
+it	O
+was	O
+localized	O
+to	O
+the	O
+nucleus	O
+and	O
+enriched	O
+in	O
+the	O
+nucleolus	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+This	O
+strongly	O
+suggests	O
+that	O
+the	O
+conserved	O
+function	O
+of	O
+Enp1	O
+is	O
+in	O
+rRNA	O
+processing	O
+.	O
+
+The	O
+cytoplasmic	O
+localization	O
+of	O
+bystin	O
+and	O
+its	O
+proposed	O
+function	O
+in	O
+cell	O
+adhesion	O
+are	O
+unlikely	O
+to	O
+reflect	O
+the	O
+actual	O
+function	O
+of	O
+the	O
+human	B
+Enp1	O
+homolog	O
+.	O
+
+It	O
+will	O
+be	O
+important	O
+to	O
+study	O
+the	O
+nature	O
+of	O
+the	O
+associations	O
+between	O
+Enp1	O
+and	O
+U3	O
+and	O
+U14	O
+snoRNPs	O
+,	O
+and	O
+to	O
+learn	O
+more	O
+about	O
+the	O
+exact	O
+role	O
+of	O
+Enp1	O
+in	O
+ribosomal	O
+RNA	O
+processing	O
+.	O
+
+Piezoelectric	O
+osteotomy	O
+in	O
+hand	O
+surgery	O
+:	O
+first	O
+experiences	O
+with	O
+a	O
+new	O
+technique	O
+
+Abstract	O
+
+Background	O
+
+In	O
+hand	O
+and	O
+spinal	O
+surgery	O
+nerve	O
+lesions	O
+are	O
+feared	O
+complications	O
+with	O
+the	O
+use	O
+of	O
+standard	O
+oscillating	O
+saws	O
+.	O
+
+Oral	O
+surgeons	O
+have	O
+started	O
+using	O
+a	O
+newly	O
+developed	O
+ultrasound	O
+bone	O
+scalpel	O
+when	O
+performing	O
+precise	O
+osteotomies	O
+.	O
+
+By	O
+using	O
+a	O
+frequency	O
+of	O
+25	O
+-	O
+29	O
+kHz	O
+only	O
+mineralized	O
+tissue	O
+is	O
+cut	O
+,	O
+sparing	O
+the	O
+soft	O
+tissue	O
+.	O
+
+This	O
+reduces	O
+the	O
+risk	O
+of	O
+nerve	O
+lesions	O
+.	O
+
+As	O
+there	O
+is	O
+a	O
+lack	O
+of	O
+experience	O
+with	O
+this	O
+technique	O
+in	O
+the	O
+field	O
+of	O
+orthopaedic	O
+bone	O
+surgery	O
+,	O
+we	O
+performed	O
+the	O
+first	O
+ultrasound	O
+osteotomy	O
+in	O
+hand	O
+surgery	O
+.	O
+
+Method	O
+
+While	O
+performing	O
+a	O
+correctional	O
+osteotomy	O
+of	O
+the	O
+5th	O
+metacarpal	O
+bone	O
+we	O
+used	O
+the	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+Device	O
+from	O
+Mectron	O
+[	O
+Italy	O
+]	O
+instead	O
+of	O
+the	O
+usual	O
+oscillating	O
+saw	O
+.	O
+
+We	O
+will	O
+report	O
+on	O
+our	O
+experience	O
+with	O
+one	O
+case	O
+,	O
+with	O
+a	O
+follow	O
+up	O
+time	O
+of	O
+one	O
+year	O
+.	O
+
+Results	O
+
+The	O
+cut	O
+was	O
+highly	O
+precise	O
+and	O
+there	O
+were	O
+no	O
+vibrations	O
+of	O
+the	O
+bone	O
+.	O
+
+The	O
+time	O
+needed	O
+for	O
+the	O
+operation	O
+was	O
+slightly	O
+longer	O
+than	O
+the	O
+time	O
+needed	O
+while	O
+using	O
+the	O
+usual	O
+saw	O
+.	O
+
+Bone	O
+healing	O
+was	O
+good	O
+and	O
+at	O
+no	O
+point	O
+were	O
+there	O
+any	O
+neurovascular	O
+disturbances	O
+.	O
+
+Conclusion	O
+
+The	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+Device	O
+is	O
+useful	O
+for	O
+small	O
+long	O
+bone	O
+osteotomies	O
+.	O
+
+Using	O
+the	O
+fine	O
+tip	O
+enables	O
+curved	O
+cutting	O
+and	O
+provides	O
+an	O
+opportunity	O
+for	O
+new	O
+osteotomy	O
+techniques	O
+.	O
+
+As	O
+the	O
+device	O
+selectively	O
+cuts	O
+bone	O
+we	O
+feel	O
+that	O
+this	O
+device	O
+has	O
+great	O
+potential	O
+in	O
+the	O
+field	O
+of	O
+hand	O
+-	O
+and	O
+spinal	O
+surgery	O
+.	O
+
+Background	O
+
+For	O
+osteotomies	O
+of	O
+the	O
+hand	O
+oscillating	O
+saws	O
+are	O
+usually	O
+used	O
+[	O
+1	O
+]	O
+.	O
+
+Even	O
+though	O
+they	O
+are	O
+varied	O
+in	O
+size	O
+,	O
+they	O
+are	O
+not	O
+very	O
+precise	O
+for	O
+use	O
+in	O
+the	O
+vicinity	O
+of	O
+nerves	O
+and	O
+arteries	O
+.	O
+
+They	O
+also	O
+pose	O
+problems	O
+while	O
+being	O
+used	O
+in	O
+conjunction	O
+with	O
+magnification	O
+,	O
+as	O
+one	O
+'	O
+s	O
+range	O
+of	O
+sight	O
+and	O
+focus	O
+is	O
+restricted	O
+when	O
+wearing	O
+magnifying	O
+glasses	O
+.	O
+
+For	O
+that	O
+reason	O
+oral	O
+surgeons	O
+have	O
+moved	O
+to	O
+using	O
+the	O
+newly	O
+developed	O
+piezoelectrical	O
+bone	O
+scalpel	O
+when	O
+operating	O
+in	O
+the	O
+near	O
+vicinity	O
+of	O
+nerves	O
+or	O
+arteries	O
+.	O
+
+The	O
+tip	O
+of	O
+this	O
+instrument	O
+oscillates	O
+in	O
+the	O
+frequency	O
+of	O
+ultrasound	O
+[	O
+2	O
+]	O
+.	O
+
+The	O
+mechanism	O
+of	O
+this	O
+device	O
+is	O
+based	O
+on	O
+the	O
+so	O
+called	O
+Piezo	O
+-	O
+Effect	O
+.	O
+
+French	O
+Physicists	O
+Jean	O
+and	O
+Marie	O
+Curie	O
+first	O
+mentioned	O
+the	O
+direct	O
+Piezo	O
+-	O
+Effect	O
+1880	O
+,	O
+whereby	O
+certain	O
+crystals	O
+produce	O
+electrical	O
+current	O
+while	O
+under	O
+mechanical	O
+pressure	O
+.	O
+
+The	O
+reciprocal	O
+effect	O
+,	O
+by	O
+which	O
+the	O
+crystals	O
+are	O
+deformed	O
+when	O
+under	O
+electrical	O
+current	O
+,	O
+was	O
+then	O
+discovered	O
+a	O
+while	O
+later	O
+.	O
+
+This	O
+is	O
+the	O
+effect	O
+being	O
+used	O
+by	O
+the	O
+Piezosurgery	O
+Device	O
+(	O
+R	O
+)	O
+.	O
+
+In	O
+this	O
+device	O
+,	O
+the	O
+electrical	O
+field	O
+is	O
+located	O
+in	O
+the	O
+handle	O
+of	O
+the	O
+saw	O
+[	O
+3	O
+]	O
+.	O
+
+Due	O
+to	O
+the	O
+deformation	O
+caused	O
+by	O
+the	O
+electrical	O
+current	O
+,	O
+a	O
+cutting	O
+-	O
+hammering	O
+movement	O
+is	O
+produced	O
+at	O
+the	O
+tip	O
+of	O
+the	O
+instrument	O
+.	O
+
+These	O
+micro	O
+movements	O
+are	O
+in	O
+the	O
+frequency	O
+range	O
+of	O
+25	O
+to	O
+29	O
+kHz	O
+and	O
+,	O
+depending	O
+on	O
+the	O
+insert	O
+,	O
+with	O
+an	O
+amplitude	O
+of	O
+60	O
+to	O
+210	O
+mu	O
+m	O
+.	O
+
+This	O
+way	O
+only	O
+mineralized	O
+tissue	O
+is	O
+selectively	O
+cut	O
+.	O
+
+Neurovascular	O
+tissue	O
+and	O
+other	O
+soft	O
+tissue	O
+would	O
+only	O
+be	O
+cut	O
+by	O
+a	O
+frequency	O
+of	O
+above	O
+50	O
+kHz	O
+[	O
+3	O
+-	O
+5	O
+]	O
+.	O
+
+Depending	O
+on	O
+the	O
+strength	O
+of	O
+the	O
+bone	O
+and	O
+the	O
+blade	O
+geometry	O
+,	O
+the	O
+efficiency	O
+of	O
+the	O
+cutting	O
+can	O
+be	O
+regulated	O
+by	O
+the	O
+frequency	O
+modulator	O
+and	O
+the	O
+power	O
+level	O
+.	O
+
+For	O
+cooling	O
+there	O
+is	O
+an	O
+integrated	O
+pump	O
+with	O
+five	O
+different	O
+working	O
+levels	O
+.	O
+
+This	O
+pump	O
+automatically	O
+washes	O
+physiological	O
+solution	O
+to	O
+the	O
+area	O
+being	O
+cut	O
+.	O
+
+The	O
+cost	O
+of	O
+the	O
+device	O
+is	O
+about	O
+7	O
+.	O
+000	O
+USD	O
+.	O
+
+Additional	O
+costs	O
+per	O
+operation	O
+are	O
+for	O
+the	O
+cooling	O
+liquid	O
+and	O
+are	O
+in	O
+the	O
+range	O
+of	O
+a	O
+few	O
+dollars	O
+.	O
+
+We	O
+have	O
+used	O
+the	O
+Piezosurgery	O
+Device	O
+(	O
+R	O
+)	O
+by	O
+Mectron	O
+[	O
+Italy	O
+]	O
+[	O
+3	O
+]	O
+for	O
+the	O
+first	O
+time	O
+in	O
+osteotomies	O
+of	O
+the	O
+long	O
+bone	O
+in	O
+the	O
+field	O
+of	O
+hand	O
+surgery	O
+.	O
+
+We	O
+will	O
+report	O
+on	O
+our	O
+experience	O
+with	O
+one	O
+case	O
+,	O
+with	O
+a	O
+follow	O
+up	O
+time	O
+of	O
+one	O
+year	O
+.	O
+
+Method	O
+
+The	O
+correctional	O
+osteotomy	O
+was	O
+performed	O
+on	O
+a	O
+23	O
+year	O
+old	O
+worker	O
+who	O
+suffered	O
+a	O
+malunited	O
+metacarpal	O
+bone	O
+fracture	O
+of	O
+the	O
+fifth	O
+finger	O
+on	O
+his	O
+dominant	O
+hand	O
+.	O
+
+The	O
+X	O
+-	O
+ray	O
+revealed	O
+a	O
+45	O
+degree	O
+angular	O
+deformity	O
+of	O
+the	O
+fifth	O
+metacarpal	O
+neck	O
+with	O
+internal	O
+rotation	O
+.	O
+
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+The	O
+operation	O
+was	O
+performed	O
+under	O
+regional	O
+anesthesia	O
+.	O
+
+A	O
+longitudinal	O
+incision	O
+was	O
+made	O
+over	O
+the	O
+fifth	O
+metacarpal	O
+.	O
+
+The	O
+tendon	O
+of	O
+the	O
+extensor	O
+digiti	O
+minimi	O
+was	O
+found	O
+and	O
+on	O
+its	O
+radial	O
+side	O
+the	O
+periosteum	O
+of	O
+metacarpal	O
+five	O
+was	O
+reached	O
+.	O
+
+The	O
+periosteum	O
+was	O
+opened	O
+longitudinally	O
+over	O
+the	O
+defect	O
+as	O
+usual	O
+.	O
+
+For	O
+the	O
+correction	O
+of	O
+the	O
+defect	O
+of	O
+45	O
+degrees	O
+,	O
+a	O
+bone	O
+wedge	O
+was	O
+excised	O
+.	O
+
+Instead	O
+of	O
+using	O
+the	O
+traditional	O
+oscillating	O
+saw	O
+,	O
+the	O
+Piezosurgery	O
+Device	O
+(	O
+R	O
+)	O
+[	O
+3	O
+]	O
+was	O
+used	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+We	O
+used	O
+a	O
+sharp	O
+hardened	O
+saw	O
+coated	O
+with	O
+titannitrid	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+For	O
+most	O
+of	O
+the	O
+surgery	O
+the	O
+highest	O
+power	O
+level	O
+,	O
+the	O
+boosted	O
+burst	O
+c	O
+,	O
+was	O
+used	O
+.	O
+
+We	O
+set	O
+the	O
+automatic	O
+cooling	O
+of	O
+the	O
+area	O
+with	O
+water	O
+to	O
+its	O
+highest	O
+level	O
+.	O
+
+The	O
+angulation	O
+and	O
+rotation	O
+was	O
+corrected	O
+and	O
+fixed	O
+with	O
+a	O
+1	O
+.	O
+5	O
+mm	O
+titanium	O
+five	O
+-	O
+hole	O
+plate	O
+and	O
+four	O
+screws	O
+.	O
+
+Closure	O
+of	O
+the	O
+wound	O
+was	O
+done	O
+in	O
+layers	O
+.	O
+
+Mobilization	O
+was	O
+started	O
+on	O
+the	O
+10th	O
+postoperative	O
+day	O
+.	O
+
+The	O
+overall	O
+time	O
+of	O
+observation	O
+was	O
+one	O
+year	O
+.	O
+
+Results	O
+and	O
+discussion	O
+
+The	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+Device	O
+is	O
+ideally	O
+sized	O
+for	O
+hand	O
+surgery	O
+.	O
+
+The	O
+cutting	O
+was	O
+very	O
+precise	O
+.	O
+
+The	O
+edges	O
+of	O
+the	O
+osteotomy	O
+were	O
+all	O
+sharp	O
+to	O
+the	O
+edge	O
+,	O
+there	O
+was	O
+no	O
+need	O
+to	O
+split	O
+the	O
+bone	O
+with	O
+a	O
+chisel	O
+,	O
+nor	O
+was	O
+there	O
+the	O
+danger	O
+of	O
+a	O
+break	O
+out	O
+.	O
+
+During	O
+the	O
+osteotomy	O
+there	O
+were	O
+no	O
+disturbing	O
+vibrations	O
+in	O
+the	O
+area	O
+of	O
+operation	O
+.	O
+
+This	O
+absence	O
+of	O
+vibration	O
+is	O
+very	O
+practical	O
+for	O
+operations	O
+using	O
+a	O
+magnifier	O
+.	O
+
+Vercellotti	O
+mentions	O
+that	O
+to	O
+overcome	O
+any	O
+problems	O
+during	O
+surgery	O
+,	O
+instead	O
+of	O
+increasing	O
+pressure	O
+on	O
+the	O
+hand	O
+piece	O
+,	O
+as	O
+in	O
+traditional	O
+techniques	O
+,	O
+it	O
+is	O
+necessary	O
+to	O
+find	O
+the	O
+correct	O
+pressure	O
+to	O
+achieve	O
+the	O
+desired	O
+result	O
+.	O
+
+With	O
+piezoelectric	O
+surgery	O
+,	O
+increasing	O
+the	O
+working	O
+pressure	O
+above	O
+a	O
+certain	O
+limit	O
+impedes	O
+the	O
+vibrations	O
+of	O
+the	O
+insert	O
+[	O
+4	O
+]	O
+.	O
+
+We	O
+have	O
+also	O
+experienced	O
+this	O
+in	O
+our	O
+study	O
+.	O
+
+The	O
+instrument	O
+can	O
+be	O
+moved	O
+in	O
+all	O
+directions	O
+comparable	O
+to	O
+a	O
+pen	O
+.	O
+
+The	O
+tip	O
+of	O
+the	O
+instrument	O
+is	O
+exchangeable	O
+.	O
+
+Using	O
+the	O
+fine	O
+tip	O
+enables	O
+multiplanar	O
+as	O
+well	O
+as	O
+curved	O
+cutting	O
+.	O
+
+Because	O
+of	O
+the	O
+automatic	O
+water	O
+cooling	O
+during	O
+the	O
+whole	O
+procedure	O
+,	O
+there	O
+is	O
+always	O
+a	O
+clear	O
+view	O
+onto	O
+the	O
+object	O
+.	O
+
+This	O
+is	O
+something	O
+oral	O
+surgeons	O
+found	O
+especially	O
+useful	O
+[	O
+6	O
+]	O
+.	O
+
+The	O
+authors	O
+mention	O
+that	O
+the	O
+downside	O
+of	O
+the	O
+device	O
+is	O
+the	O
+relative	O
+slow	O
+sawing	O
+process	O
+.	O
+
+We	O
+needed	O
+about	O
+30	O
+seconds	O
+for	O
+one	O
+cut	O
+of	O
+the	O
+relatively	O
+small	O
+bone	O
+.	O
+
+This	O
+is	O
+about	O
+20	O
+seconds	O
+longer	O
+than	O
+the	O
+time	O
+needed	O
+for	O
+cutting	O
+with	O
+the	O
+usual	O
+saw	O
+.	O
+
+Although	O
+the	O
+power	O
+can	O
+be	O
+regulated	O
+with	O
+the	O
+power	O
+box	O
+and	O
+the	O
+use	O
+of	O
+different	O
+scalpels	O
+,	O
+we	O
+agree	O
+with	O
+other	O
+authors	O
+that	O
+the	O
+optimal	O
+use	O
+of	O
+this	O
+device	O
+is	O
+in	O
+surgeries	O
+of	O
+small	O
+bones	O
+where	O
+precise	O
+and	O
+soft	O
+tissue	O
+friendly	O
+cutting	O
+is	O
+required	O
+[	O
+7	O
+]	O
+.	O
+
+As	O
+other	O
+literature	O
+has	O
+shown	O
+,	O
+the	O
+device	O
+selectively	O
+cuts	O
+bone	O
+while	O
+sparing	O
+nerves	O
+and	O
+other	O
+soft	O
+tissue	O
+[	O
+2	O
+,	O
+3	O
+]	O
+.	O
+
+This	O
+allows	O
+for	O
+minimal	O
+invasive	O
+surgeries	O
+with	O
+limited	O
+retraction	O
+of	O
+soft	O
+tissue	O
+and	O
+minimal	O
+stripping	O
+of	O
+the	O
+periosteum	O
+,	O
+saves	O
+time	O
+and	O
+might	O
+have	O
+a	O
+positive	O
+effect	O
+on	O
+the	O
+healing	O
+process	O
+.	O
+
+Our	O
+aim	O
+of	O
+the	O
+first	O
+time	O
+use	O
+of	O
+the	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+Device	O
+in	O
+hand	O
+surgery	O
+was	O
+to	O
+check	O
+its	O
+usability	O
+in	O
+osteotomies	O
+of	O
+tubular	O
+bones	O
+.	O
+
+The	O
+preparation	O
+of	O
+the	O
+bone	O
+was	O
+done	O
+in	O
+the	O
+usual	O
+manner	O
+as	O
+is	O
+done	O
+when	O
+cutting	O
+with	O
+an	O
+oscillating	O
+saw	O
+.	O
+
+The	O
+reason	O
+for	O
+this	O
+was	O
+to	O
+fully	O
+visualize	O
+the	O
+cutting	O
+process	O
+using	O
+this	O
+new	O
+device	O
+,	O
+although	O
+in	O
+the	O
+future	O
+,	O
+it	O
+should	O
+be	O
+possible	O
+to	O
+minimize	O
+the	O
+bony	O
+exposure	O
+.	O
+
+In	O
+our	O
+patient	B
+the	O
+postoperative	O
+healing	O
+of	O
+the	O
+wound	O
+and	O
+the	O
+bone	O
+consolidation	O
+(	O
+Figure	O
+4	O
+)	O
+were	O
+smooth	O
+.	O
+
+The	O
+duration	O
+of	O
+postoperative	O
+sick	O
+leave	O
+was	O
+four	O
+weeks	O
+which	O
+is	O
+more	O
+rapid	O
+than	O
+the	O
+usual	O
+recovery	O
+period	O
+.	O
+
+The	O
+patient	B
+regained	O
+full	O
+use	O
+of	O
+his	O
+finger	O
+according	O
+to	O
+the	O
+state	O
+before	O
+the	O
+fracture	O
+.	O
+
+At	O
+no	O
+point	O
+was	O
+there	O
+any	O
+loss	O
+of	O
+sensitivity	O
+.	O
+
+The	O
+patient	B
+as	O
+well	O
+as	O
+the	O
+surgeons	O
+were	O
+fully	O
+satisfied	O
+with	O
+the	O
+result	O
+.	O
+
+Conclusion	O
+
+The	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+Device	O
+is	O
+a	O
+useful	O
+device	O
+for	O
+small	O
+long	O
+bone	O
+osteotomies	O
+.	O
+
+We	O
+feel	O
+that	O
+this	O
+device	O
+has	O
+great	O
+potential	O
+in	O
+the	O
+field	O
+of	O
+hand	O
+-	O
+and	O
+spinal	O
+surgery	O
+.	O
+
+As	O
+the	O
+device	O
+selectively	O
+cuts	O
+bone	O
+,	O
+considerable	O
+nerve	O
+lesions	O
+can	O
+be	O
+avoided	O
+and	O
+minimal	O
+invasive	O
+surgeries	O
+are	O
+possible	O
+.	O
+
+Using	O
+the	O
+fine	O
+tip	O
+enables	O
+curved	O
+cutting	O
+and	O
+provides	O
+an	O
+opportunity	O
+for	O
+new	O
+osteotomy	O
+techniques	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+DJH	O
+initiated	O
+and	O
+coordinated	O
+the	O
+new	O
+application	O
+of	O
+Piezosurgery	O
+(	O
+R	O
+)	O
+device	O
+and	O
+wrote	O
+the	O
+publication	O
+.	O
+
+StSt	O
+lead	O
+the	O
+osteotomy	O
+as	O
+he	O
+was	O
+experienced	O
+with	O
+this	O
+tool	O
+from	O
+oral	O
+surgery	O
+.	O
+
+He	O
+played	O
+a	O
+major	O
+part	O
+in	O
+writing	O
+the	O
+technical	O
+aspects	O
+.	O
+
+OVK	O
+was	O
+the	O
+treating	O
+surgeon	O
+,	O
+performed	O
+the	O
+operation	O
+and	O
+evaluated	O
+the	O
+new	O
+tool	O
+.	O
+
+SS	O
+performed	O
+a	O
+literature	O
+review	O
+and	O
+wrote	O
+part	O
+of	O
+the	O
+publication	O
+.	O
+
+PH	O
+was	O
+the	O
+treating	O
+chief	O
+surgeon	O
+,	O
+evaluated	O
+the	O
+new	O
+tool	O
+and	O
+lead	O
+the	O
+treatment	O
+in	O
+all	O
+aspects	O
+.	O
+
+Consent	O
+
+We	O
+obtained	O
+oral	O
+consent	O
+from	O
+the	O
+patient	B
+but	O
+could	O
+not	O
+obtain	O
+written	O
+consent	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+Molecular	O
+cloning	O
+of	O
+four	O
+novel	O
+murine	B
+ribonuclease	O
+genes	O
+:	O
+unusual	O
+expansion	O
+within	O
+the	O
+ribonuclease	O
+A	O
+gene	O
+family	O
+.	O
+
+Abstract	O
+
+We	O
+have	O
+characterized	O
+four	O
+novel	O
+murine	B
+ribonuclease	O
+genes	O
+that	O
+,	O
+together	O
+with	O
+the	O
+murine	B
+eosinophil	O
+-	O
+associated	O
+ribonucleases	O
+1	O
+and	O
+2	O
+,	O
+form	O
+a	O
+distinct	O
+and	O
+unusual	O
+cluster	O
+within	O
+the	O
+RNase	O
+A	O
+gene	O
+superfamily	O
+.	O
+
+Three	O
+of	O
+these	O
+genes	O
+(	O
+mR	O
+-	O
+3	O
+,	O
+mR	O
+-	O
+4	O
+,	O
+mR	O
+-	O
+5	O
+)	O
+include	O
+complete	O
+open	O
+reading	O
+frames	O
+,	O
+encoding	O
+ribonucleases	O
+with	O
+eight	O
+cysteines	O
+and	O
+appropriately	O
+spaced	O
+histidines	O
+(	O
+His11	O
+and	O
+His124	O
+)	O
+and	O
+lysine	O
+(	O
+Lys35	O
+)	O
+that	O
+are	O
+characteristic	O
+of	O
+this	O
+enlarging	O
+protein	O
+family	O
+;	O
+the	O
+fourth	O
+sequence	O
+encodes	O
+a	O
+non	O
+-	O
+functional	O
+pseudogene	O
+(	O
+mR	O
+-	O
+6P	O
+)	O
+.	O
+
+Although	O
+the	O
+amino	O
+acid	O
+sequence	O
+similarities	O
+among	O
+these	O
+murine	B
+ribonucleases	O
+varies	O
+from	O
+60	O
+to	O
+94	O
+%	O
+,	O
+they	O
+form	O
+a	O
+unique	O
+cluster	O
+,	O
+as	O
+each	O
+sequence	O
+is	O
+found	O
+to	O
+be	O
+more	O
+closely	O
+related	O
+to	O
+another	O
+of	O
+this	O
+group	O
+than	O
+to	O
+either	O
+murine	B
+angiogenin	O
+or	O
+to	O
+murine	B
+pancreatic	O
+ribonuclease	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+relationship	O
+between	O
+the	O
+six	O
+genes	O
+in	O
+this	O
+'	O
+mR	O
+cluster	O
+'	O
+and	O
+the	O
+defined	O
+lineages	O
+of	O
+the	O
+RNase	O
+A	O
+gene	O
+family	O
+could	O
+not	O
+be	O
+determined	O
+by	O
+amino	O
+acid	O
+sequence	O
+homology	O
+,	O
+suggesting	O
+the	O
+possibility	O
+that	O
+there	O
+are	O
+one	O
+or	O
+more	O
+additional	O
+ribonuclease	O
+lineages	O
+that	O
+have	O
+yet	O
+to	O
+be	O
+defined	O
+.	O
+
+Although	O
+the	O
+nature	O
+of	O
+the	O
+evolutionary	O
+constraints	O
+promoting	O
+this	O
+unusual	O
+expansion	O
+and	O
+diversification	O
+remain	O
+unclear	O
+,	O
+the	O
+implications	O
+with	O
+respect	O
+to	O
+function	O
+are	O
+intriguing	O
+.	O
+
+<	O
+FFFD	O
+>	O
+1997	O
+Oxford	O
+University	O
+Press	O
+
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1997	O
+,	O
+Vol	O
+.	O
+
+25	O
+,	O
+No	O
+.	O
+21	O
+
+4235	O
+<	O
+FFFD	O
+>	O
+4239	O
+
+Molecular	O
+cloning	O
+of	O
+four	O
+novel	O
+murine	B
+ribonuclease	O
+genes	O
+:	O
+unusual	O
+expansion	O
+within	O
+the	O
+Ribonuclease	O
+A	O
+gene	O
+family	O
+Dean	O
+Batten	O
++	O
+,	O
+Kimberly	O
+D	O
+.	O
+Dyer	O
+,	O
+Joseph	O
+B	O
+.	O
+Domachowske	O
+<	O
+FFFD	O
+>	O
+and	O
+Helene	O
+F	O
+.	O
+Rosenberg	O
+*	O
+The	O
+Laboratory	O
+of	O
+Host	O
+Defenses	O
+,	O
+Building	O
+10	O
+,	O
+Room	O
+11N104	O
+,	O
+National	O
+Institute	O
+of	O
+Allergy	O
+and	O
+Infectious	O
+Diseases	O
+,	O
+National	O
+Institutes	O
+of	O
+Health	O
+,	O
+9000	O
+Rockville	O
+Pike	O
+,	O
+Bethesda	O
+,	O
+MD	O
+20892	O
+,	O
+USA	O
+Received	O
+August	O
+4	O
+,	O
+1997	O
+;	O
+Revised	O
+and	O
+Accepted	O
+September	O
+17	O
+,	O
+1997	O
+DDBJ	O
+/	O
+EMBL	O
+/	O
+GenBank	O
+accession	O
+numbers	O
+:	O
+U72031	O
+,	O
+U72032	O
+,	O
+AF017258	O
+<	O
+FFFD	O
+>	O
+AF017261	O
+
+ABSTRACT	O
+We	O
+have	O
+characterized	O
+four	O
+novel	O
+murine	B
+ribonuclease	O
+genes	O
+that	O
+,	O
+together	O
+with	O
+the	O
+murine	B
+eosinophilassociated	O
+ribonucleases	O
+1	O
+and	O
+2	O
+,	O
+form	O
+a	O
+distinct	O
+and	O
+unusual	O
+cluster	O
+within	O
+the	O
+RNase	O
+A	O
+gene	O
+superfamily	O
+.	O
+
+Three	O
+of	O
+these	O
+genes	O
+(	O
+mR	O
+-	O
+3	O
+,	O
+mR	O
+-	O
+4	O
+,	O
+mR	O
+-	O
+5	O
+)	O
+include	O
+complete	O
+open	O
+reading	O
+frames	O
+,	O
+encoding	O
+ribonucleases	O
+with	O
+eight	O
+cysteines	O
+and	O
+appropriately	O
+spaced	O
+histidines	O
+(	O
+His11	O
+and	O
+His124	O
+)	O
+and	O
+lysine	O
+(	O
+Lys35	O
+)	O
+that	O
+are	O
+characteristic	O
+of	O
+this	O
+enlarging	O
+protein	O
+family	O
+;	O
+the	O
+fourth	O
+sequence	O
+encodes	O
+a	O
+non	O
+-	O
+functional	O
+pseudogene	O
+(	O
+mR	O
+-	O
+6P	O
+)	O
+.	O
+
+Although	O
+the	O
+amino	O
+acid	O
+sequence	O
+similarities	O
+among	O
+these	O
+murine	B
+ribonucleases	O
+varies	O
+from	O
+60	O
+to	O
+94	O
+%	O
+,	O
+they	O
+form	O
+a	O
+unique	O
+cluster	O
+,	O
+as	O
+each	O
+sequence	O
+is	O
+found	O
+to	O
+be	O
+more	O
+closely	O
+related	O
+to	O
+another	O
+of	O
+this	O
+group	O
+than	O
+to	O
+either	O
+murine	B
+angiogenin	O
+or	O
+to	O
+murine	B
+pancreatic	O
+ribonuclease	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+relationship	O
+between	O
+the	O
+six	O
+genes	O
+in	O
+this	O
+`	O
+mR	O
+cluster	O
+'	O
+and	O
+the	O
+defined	O
+lineages	O
+of	O
+the	O
+RNase	O
+A	O
+gene	O
+family	O
+could	O
+not	O
+be	O
+determined	O
+by	O
+amino	O
+acid	O
+sequence	O
+homology	O
+,	O
+suggesting	O
+the	O
+possibility	O
+that	O
+there	O
+are	O
+one	O
+or	O
+more	O
+additional	O
+ribonuclease	O
+lineages	O
+that	O
+have	O
+yet	O
+to	O
+be	O
+defined	O
+.	O
+
+Although	O
+the	O
+nature	O
+of	O
+the	O
+evolutionary	O
+constraints	O
+promoting	O
+this	O
+unusual	O
+expansion	O
+and	O
+diversification	O
+remain	O
+unclear	O
+,	O
+the	O
+implications	O
+with	O
+respect	O
+to	O
+function	O
+are	O
+intriguing	O
+.	O
+
+INTRODUCTION	O
+Ribonuclease	O
+A	O
+(	O
+RNase	O
+A	O
+,	O
+bovine	B
+pancreatic	O
+ribonuclease	O
+)	O
+is	O
+the	O
+prototype	O
+of	O
+an	O
+enlarging	O
+family	O
+of	O
+proteins	O
+defined	O
+by	O
+distinctive	O
+elements	O
+of	O
+conserved	O
+primary	O
+structure	O
+and	O
+enzymatic	O
+activity	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+The	O
+features	O
+shared	O
+by	O
+all	O
+members	O
+of	O
+the	O
+RNase	O
+A	O
+family	O
+include	O
+six	O
+to	O
+eight	O
+cysteines	O
+and	O
+specific	O
+histidine	O
+and	O
+lysine	O
+residues	O
+that	O
+form	O
+the	O
+ribonuclease	O
+active	O
+site	O
+.	O
+
+To	O
+date	O
+,	O
+several	O
+distinct	O
+lineages	O
+within	O
+the	O
+RNase	O
+A	O
+superfamily	O
+have	O
+been	O
+identified	O
+.	O
+
+Pancreatic	O
+ribonucleases	O
+(	O
+RNases	O
+1	O
+)	O
+have	O
+been	O
+isolated	O
+from	O
+an	O
+extensive	O
+array	O
+of	O
+mammalian	O
+species	O
+(	O
+3	O
+,	O
+4	O
+)	O
+,	O
+and	O
+mRNA	O
+encoding	O
+human	B
+pancreatic	O
+ribonuclease	O
+has	O
+been	O
+detected	O
+in	O
+
+numerous	O
+somatic	O
+tissues	O
+in	O
+addition	O
+to	O
+pancreas	O
+(	O
+5	O
+)	O
+.	O
+
+RNases	O
+2	O
+and	O
+3	O
+,	O
+eosinophil	O
+-	O
+derived	O
+neurotoxin	O
+(	O
+EDN	O
+)	O
+and	O
+eosinophil	O
+cationic	O
+protein	O
+(	O
+ECP	O
+)	O
+,	O
+respectively	O
+,	O
+have	O
+been	O
+characterized	O
+primarily	O
+with	O
+respect	O
+to	O
+eosinophil	O
+function	O
+(	O
+6	O
+,	O
+7	O
+)	O
+,	O
+although	O
+expression	O
+of	O
+EDN	O
+[	O
+also	O
+known	O
+as	O
+RNase	O
+Us	O
+(	O
+8	O
+)	O
+or	O
+human	B
+liver	O
+ribonuclease	O
+(	O
+9	O
+)	O
+]	O
+is	O
+also	O
+widespread	O
+(	O
+5	O
+)	O
+.	O
+
+Angiogenin	O
+(	O
+RNase	O
+5	O
+)	O
+,	O
+a	O
+structurally	O
+atypical	O
+member	O
+of	O
+this	O
+family	O
+,	O
+was	O
+originally	O
+identified	O
+as	O
+an	O
+agent	O
+promoting	O
+blood	O
+vessel	O
+growth	O
+and	O
+development	O
+(	O
+10	O
+,	O
+11	O
+)	O
+.	O
+
+RNase	O
+4	O
+(	O
+12	O
+,	O
+13	O
+)	O
+and	O
+RNase	O
+k6	O
+(	O
+14	O
+)	O
+are	O
+also	O
+members	O
+of	O
+the	O
+RNase	O
+A	O
+superfamily	O
+,	O
+although	O
+their	O
+functions	O
+are	O
+currently	O
+obscure	O
+.	O
+
+Recently	O
+,	O
+Larson	O
+and	O
+colleagues	O
+(	O
+15	O
+)	O
+described	O
+cDNAs	O
+encoding	O
+two	O
+highly	O
+homologous	O
+murine	B
+ribonucleases	O
+,	O
+the	O
+murine	B
+eosinophil	O
+-	O
+associated	O
+ribonucleases	O
+(	O
+mEAR	O
+)	O
+1	O
+and	O
+2	O
+,	O
+which	O
+were	O
+cloned	O
+and	O
+identified	O
+via	O
+tryptic	O
+peptides	O
+isolated	O
+from	O
+murine	B
+eosinophil	O
+proteins	O
+.	O
+
+Although	O
+Southern	O
+analysis	O
+demonstrated	O
+that	O
+multiple	O
+copies	O
+of	O
+sequence	O
+homologous	O
+to	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+were	O
+present	O
+in	O
+murine	B
+genomic	O
+DNA	O
+,	O
+the	O
+precise	O
+nature	O
+of	O
+these	O
+copies	O
+-	O
+-	O
+as	O
+pseudogenes	O
+,	O
+polymorphisms	O
+,	O
+or	O
+distinct	O
+functional	O
+genes	O
+-	O
+-	O
+was	O
+unclear	O
+.	O
+
+In	O
+this	O
+work	O
+,	O
+we	O
+have	O
+identified	O
+four	O
+of	O
+these	O
+homologous	O
+sequences	O
+,	O
+three	O
+encoding	O
+novel	O
+ribonucleases	O
+,	O
+and	O
+one	O
+encoding	O
+a	O
+pseudogene	O
+.	O
+
+Together	O
+with	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+,	O
+these	O
+six	O
+ribonuclease	O
+genes	O
+form	O
+an	O
+`	O
+mR	O
+cluster	O
+,	O
+'	O
+whose	O
+members	O
+are	O
+more	O
+closely	O
+related	O
+to	O
+one	O
+another	O
+than	O
+they	O
+are	O
+to	O
+other	O
+murine	B
+ribonucleases	O
+,	O
+yet	O
+whose	O
+position	O
+with	O
+respect	O
+to	O
+the	O
+defined	O
+RNase	O
+A	O
+lineages	O
+remains	O
+unclear	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+Isolation	O
+of	O
+genomic	O
+fragments	O
+encoding	O
+murine	B
+ribonucleases	O
+by	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+Genomic	O
+DNA	O
+was	O
+isolated	O
+from	O
+cells	O
+of	O
+the	O
+murine	B
+3T3	O
+fibroblast	O
+cell	O
+line	O
+.	O
+
+The	O
+mR	O
+-	O
+3	O
+,	O
+mR	O
+-	O
+5	O
+and	O
+mR	O
+-	O
+6P	O
+sequences	O
+were	O
+amplified	O
+using	O
+oligonucleotide	O
+primers	O
+derived	O
+from	O
+the	O
+published	O
+coding	O
+sequence	O
+of	O
+mEAR	O
+-	O
+1	O
+as	O
+follows	O
+:	O
+5	O
+-	O
+CAA	O
+ACC	O
+CTT	O
+TCC	O
+CAG	O
+AAG	O
+TTT	O
+GCC	O
+-	O
+3	O
+(	O
+amino	O
+acids	O
+28	O
+<	O
+FFFD	O
+>	O
+33	O
+)	O
+;	O
+5	O
+-	O
+AAA	O
+TGT	O
+CCC	O
+ATC	O
+CAA	O
+GTG	O
+AAC	O
+TGG	O
+ACC	O
+-	O
+3	O
+(	O
+amino	O
+acids	O
+156	O
+<	O
+FFFD	O
+>	O
+148	O
+)	O
+(	O
+15	O
+)	O
+.	O
+
+The	O
+PCR	O
+reactions	O
+were	O
+performed	O
+as	O
+described	O
+previously	O
+(	O
+14	O
+)	O
+,	O
+and	O
+the	O
+multiple	O
+products	O
+present	O
+in	O
+the	O
+single	O
+400	O
+bp	O
+product	O
+were	O
+identified	O
+by	O
+dideoxy	O
+
+*	O
+To	O
+whom	O
+correspondence	O
+should	O
+be	O
+addressed	O
+.	O
+
+Tel	O
+:	O
++	O
+1	O
+301	O
+402	O
+9131	O
+;	O
+Fax	O
+:	O
++	O
+1	O
+301	O
+402	O
+4369	O
+;	O
+Email	O
+:	O
+hr2k	O
+@	O
+nih	O
+.	O
+gov	O
+Present	O
+addresses	O
+:	O
++	O
+Duke	O
+University	O
+School	O
+of	O
+Medicine	O
+,	O
+Durham	O
+,	O
+NC	O
+27701	O
+,	O
+USA	O
+and	O
+<	O
+FFFD	O
+>	O
+Department	O
+of	O
+Pediatrics	O
+,	O
+State	O
+University	O
+of	O
+New	O
+York	O
+-	O
+Health	O
+Sciences	O
+Center	O
+at	O
+Syracuse	O
+,	O
+Syracuse	O
+,	O
+NY	O
+13210	O
+,	O
+USA	O
+
+4236	O
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1997	O
+,	O
+Vol	O
+.	O
+
+25	O
+,	O
+No	O
+.	O
+21	O
+
+Figure	O
+1	O
+.	O
+
+(	O
+A	O
+)	O
+Alignment	O
+of	O
+amino	O
+acid	O
+sequences	O
+encoded	O
+by	O
+six	O
+related	O
+murine	B
+ribonuclease	O
+genes	O
+.	O
+
+Regions	O
+of	O
+amino	O
+acid	O
+sequence	O
+identity	O
+among	O
+the	O
+five	O
+functional	O
+genes	O
+are	O
+enclosed	O
+in	O
+boxes	O
+;	O
+the	O
+boxes	O
+enclosing	O
+the	O
+active	O
+site	O
+residues	O
+(	O
+His11	O
+,	O
+Lys35	O
+,	O
+His124	O
+)	O
+and	O
+eight	O
+cysteines	O
+conserved	O
+in	O
+all	O
+members	O
+of	O
+the	O
+RNase	O
+A	O
+superfamily	O
+are	O
+shaded	O
+.	O
+
+(	O
+B	O
+)	O
+Percent	O
+similarities	O
+between	O
+amino	O
+acid	O
+sequences	O
+determined	O
+via	O
+the	O
+BESTFIT	O
+algorithm	O
+of	O
+the	O
+Wisconsin	O
+Genetics	O
+Computer	O
+Group	O
+(	O
+WGCG	O
+)	O
+program	O
+on	O
+-	O
+line	O
+at	O
+the	O
+National	O
+Institutes	O
+of	O
+Health	O
+.	O
+
+GenBank	O
+accession	O
+numbers	O
+:	O
+mEAR	O
+(	O
+murine	B
+eosinophil	O
+-	O
+associated	O
+ribonuclease	O
+)	O
+-	O
+1	O
+,	O
+U72032	O
+;	O
+mEAR	O
+-	O
+2	O
+,	O
+U72031	O
+;	O
+mR	O
+(	O
+murine	B
+ribonuclease	O
+)	O
+-	O
+3	O
+,	O
+AF017258	O
+;	O
+mR	O
+-	O
+4	O
+,	O
+AF017259	O
+;	O
+mR	O
+-	O
+5	O
+,	O
+AF017260	O
+;	O
+mR	O
+-	O
+6P	O
+(	O
+pseudogene	O
+)	O
+,	O
+AF017261	O
+.	O
+
+sequencing	O
+of	O
+individual	O
+plasmids	O
+after	O
+subcloning	O
+into	O
+the	O
+pCR	O
+II	O
+TA	O
+cloning	O
+vector	O
+(	O
+Invitrogen	O
+,	O
+San	O
+Diego	O
+,	O
+CA	O
+)	O
+.	O
+
+The	O
+complete	O
+open	O
+reading	O
+frames	O
+were	O
+obtained	O
+by	O
+extension	O
+in	O
+both	O
+5	O
+and	O
+3	O
+directions	O
+by	O
+uni	O
+-	O
+directional	O
+PCR	O
+(	O
+Genome	O
+Walker	O
+kit	O
+,	O
+Clontech	O
+,	O
+Palo	O
+Alto	O
+,	O
+CA	O
+)	O
+,	O
+involving	O
+two	O
+amplifications	O
+with	O
+nested	O
+primers	O
+and	O
+Tth	O
+polymerase	O
+as	O
+described	O
+previously	O
+(	O
+14	O
+)	O
+.	O
+
+The	O
+nested	O
+gene	O
+-	O
+specific	O
+primer	O
+pairs	O
+were	O
+as	O
+follows	O
+:	O
+for	O
+5	O
+extension	O
+of	O
+mR	O
+-	O
+3	O
+,	O
+5	O
+-	O
+CTG	O
+GAA	O
+CCA	O
+CTG	O
+GAT	O
+ACG	O
+TGG	O
+GAC	O
+TGT	O
+CCT	O
+-	O
+3	O
+and	O
+5	O
+-	O
+ACG	O
+TGG	O
+GAC	O
+TGT	O
+CCT	O
+GTG	O
+GAG	O
+TTC	O
+TGG	O
+GTT	O
+-	O
+3	O
+;	O
+for	O
+3	O
+extension	O
+of	O
+mR	O
+-	O
+3	O
+,	O
+5	O
+-	O
+ATG	O
+CTG	O
+TTG	O
+GTG	O
+TGT	O
+GTG	O
+GAA	O
+ATC	O
+CAA	O
+GTG	O
+-	O
+3	O
+and	O
+5	O
+-	O
+GCT	O
+TGT	O
+GCA	O
+GTG	O
+ACA	O
+ATA	O
+TAA	O
+GTC	O
+AAA	O
+ACT	O
+-	O
+3	O
+;	O
+for	O
+5	O
+extension	O
+of	O
+mR	O
+-	O
+5	O
+,	O
+5	O
+-	O
+GGT	O
+GGG	O
+ACG	O
+GTC	O
+CTT	O
+TGG	O
+AGT	O
+TCT	O
+GGG	O
+GTT	O
+ACA	O
+-	O
+3	O
+and	O
+5	O
+-	O
+GGG	O
+GTT	O
+ACA	O
+GGC	O
+AAC	O
+TGT	O
+GTA	O
+GGA	O
+CTT	O
+CTT	O
+TCC	O
+-	O
+3	O
+;	O
+for	O
+3	O
+extension	O
+of	O
+mR	O
+-	O
+5	O
+,	O
+5	O
+-	O
+GAT	O
+GTT	O
+GTC	O
+CGT	O
+GTG	O
+TGT	O
+CAC	O
+AAT	O
+CCA	O
+CCC	O
+-	O
+3	O
+and	O
+5	O
+-	O
+AAG	O
+ACT	O
+TGC	O
+AAA	O
+GAC	O
+GGG	O
+ACA	O
+AGT	O
+CCA	O
+AAT	O
+-	O
+3	O
+;	O
+for	O
+5	O
+extension	O
+of	O
+mR	O
+-	O
+6P	O
+,	O
+5	O
+-	O
+TTG	O
+TTG	O
+TTT	O
+TGC	O
+ATC	O
+TGC	O
+ATT	O
+GTG	O
+CAT	O
+AAC	O
+TGC	O
+-	O
+3	O
+and	O
+5	O
+-	O
+TTC	O
+TGC	O
+ATA	O
+ACT	O
+GCT	O
+TGC	O
+TGA	O
+ACT	O
+TGT	O
+GAG	O
+TGA	O
+-	O
+3	O
+;	O
+for	O
+3	O
+extension	O
+of	O
+mR	O
+-	O
+6P	O
+,	O
+5	O
+-	O
+ATG	O
+TGA	O
+TAA	O
+TGC	O
+AAT	O
+GCT	O
+GTC	O
+TCT	O
+TAG	O
+CAG	O
+TTA	O
+-	O
+3	O
+and	O
+5	O
+-	O
+TAC	O
+AAG	O
+
+AGT	O
+ATG	O
+TAA	O
+GCC	O
+ATT	O
+GAA	O
+TCA	O
+TTT	O
+TCT	O
+-	O
+3	O
+.	O
+
+The	O
+products	O
+of	O
+these	O
+reactions	O
+were	O
+likewise	O
+subcloned	O
+into	O
+the	O
+PCR	O
+II	O
+TA	O
+vector	O
+and	O
+evaluated	O
+by	O
+dideoxy	O
+-	O
+sequencing	O
+.	O
+
+The	O
+mR	O
+-	O
+4	O
+sequence	O
+was	O
+amplified	O
+with	O
+a	O
+36	O
+bp	O
+primer	O
+derived	O
+from	O
+sequence	O
+encoding	O
+the	O
+amino	O
+-	O
+terminal	O
+signal	O
+sequence	O
+of	O
+mEAR	O
+-	O
+1	O
+;	O
+5	O
+-	O
+ATG	O
+GGT	O
+CCG	O
+AAG	O
+CTG	O
+CTT	O
+GAG	O
+TCC	O
+CGA	O
+CTT	O
+TGT	O
+CTC	O
+-	O
+3	O
+with	O
+the	O
+carboxy	O
+-	O
+primer	O
+described	O
+above	O
+.	O
+
+Northern	O
+analysis	O
+The	O
+murine	B
+multi	O
+-	O
+tissue	O
+Northern	O
+blot	O
+was	O
+purchased	O
+from	O
+Clontech	O
+,	O
+and	O
+pre	O
+-	O
+hybridized	O
+and	O
+hybridized	O
+as	O
+per	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+with	O
+radiolabelled	O
+oligonucleotide	O
+probes	O
+.	O
+
+The	O
+membrane	O
+was	O
+washed	O
+with	O
+5	O
+<	O
+FFFD	O
+>	O
+SSPE	O
+with	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+for	O
+1	O
+h	O
+at	O
+37	O
+_	O
+C	O
+and	O
+the	O
+autoradiogram	O
+developed	O
+after	O
+exposure	O
+to	O
+film	O
+at	O
+<	O
+FFFD	O
+>	O
+80	O
+_	O
+C	O
+.	O
+
+The	O
+mEAR	O
+-	O
+1	O
+/	O
+mEAR	O
+-	O
+2	O
+/	O
+mR	O
+-	O
+3	O
+probe	O
+:	O
+5	O
+-	O
+CTC	O
+TTG	O
+TCA	O
+CTG	O
+CAC	O
+AAG	O
+CCA	O
+CTT	O
+GGA	O
+TTT	O
+CC	O
+-	O
+3	O
+,	O
+the	O
+mR	O
+-	O
+5	O
+probe	O
+:	O
+5	O
+-	O
+GTC	O
+CCG	O
+TCT	O
+TTG	O
+CAA	O
+GTC	O
+TTG	O
+GGT	O
+GGA	O
+TTG	O
+TG	O
+-	O
+3	O
+,	O
+and	O
+the	O
+actin	O
+probe	O
+:	O
+5	O
+-	O
+GCA	O
+CAT	O
+GCC	O
+GGA	O
+GCC	O
+GTT	O
+GTC	O
+GAC	O
+GAC	O
+GAG	O
+CGC	O
+GGC	O
+GAT	O
+ATC	O
+ATC	O
+ATC	O
+-	O
+3	O
+(	O
+16	O
+)	O
+.	O
+
+4237	O
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1997	O
+,	O
+Vol	O
+.	O
+
+25	O
+,	O
+No	O
+.	O
+
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1994	O
+,	O
+Vol	O
+.	O
+
+22	O
+,	O
+No	O
+.	O
+121	O
+4237	O
+
+Figure	O
+2	O
+.	O
+
+(	O
+A	O
+)	O
+Dendrogram	O
+depicting	O
+relationships	O
+among	O
+the	O
+eight	O
+characterized	O
+murine	B
+ribonucleases	O
+as	O
+determined	O
+by	O
+a	O
+modified	O
+UPGMA	O
+method	O
+(	O
+17	O
+)	O
+.	O
+
+Abbreviations	O
+are	O
+as	O
+in	O
+Figure	O
+1A	O
+,	O
+also	O
+mPR	O
+(	O
+murine	B
+pancreatic	O
+ribonuclease	O
+,	O
+sw	O
+:	O
+rnp	O
+_	O
+mouse	B
+)	O
+,	O
+mANG	O
+(	O
+murine	B
+angiogenin	O
+,	O
+U72672	O
+)	O
+,	O
+hEDN	O
+(	O
+human	B
+eosinophil	O
+-	O
+derived	O
+neurotoxin	O
+,	O
+M24157	O
+)	O
+,	O
+hECP	O
+(	O
+human	B
+eosinophil	O
+cationic	O
+protein	O
+,	O
+X15161	O
+)	O
+,	O
+hRK6	O
+(	O
+human	B
+ribonuclease	O
+k6	O
+,	O
+U64998	O
+)	O
+,	O
+pRK6	O
+(	O
+porcine	O
+kidney	O
+ribonuclease	O
+(	O
+24	O
+)	O
+,	O
+and	O
+bRK6	O
+(	O
+bovine	B
+kidney	O
+ribonuclease	O
+,	O
+sw	O
+:	O
+rnkd	O
+_	O
+bovin	O
+)	O
+.	O
+
+(	O
+B	O
+)	O
+Calculated	O
+isoelectric	O
+points	O
+from	O
+amino	O
+acid	O
+sequences	O
+in	O
+(	O
+A	O
+)	O
+as	O
+determined	O
+via	O
+the	O
+PEPTIDESORT	O
+algorithm	O
+of	O
+WGCG	O
+.	O
+
+Table	O
+1	O
+.	O
+
+Amino	O
+acid	O
+sequence	O
+comparisons	O
+of	O
+murine	B
+and	O
+human	B
+ribonucleases	O
+
+Sequence	O
+analysis	O
+All	O
+DNA	O
+sequence	O
+analysis	O
+and	O
+comparisons	O
+were	O
+performed	O
+with	O
+the	O
+assistance	O
+of	O
+the	O
+Wisconsin	O
+Genetics	O
+Computer	O
+Group	O
+and	O
+Sequencher	O
+(	O
+Gene	O
+Codes	O
+Corporation	O
+)	O
+programs	O
+available	O
+at	O
+the	O
+National	O
+Institutes	O
+of	O
+Health	O
+.	O
+
+The	O
+dendrogram	O
+in	O
+Figure	O
+2A	O
+was	O
+constructed	O
+by	O
+a	O
+modified	O
+version	O
+of	O
+the	O
+unweighted	O
+pair	O
+group	O
+method	O
+with	O
+arithmetic	O
+mean	O
+(	O
+UPGMA	O
+)	O
+(	O
+17	O
+)	O
+,	O
+constructed	O
+using	O
+four	O
+initial	O
+pairings	O
+,	O
+mEAR	O
+-	O
+2	O
+to	O
+mR	O
+-	O
+3	O
+,	O
+mR	O
+-	O
+5	O
+to	O
+mR	O
+-	O
+6P	O
+,	O
+hEDN	O
+to	O
+hECP	O
+and	O
+bRK6	O
+to	O
+pRK6	O
+.	O
+
+RESULTS	O
+Isolation	O
+of	O
+genomic	O
+fragments	O
+encoding	O
+novel	O
+murine	B
+ribonucleases	O
+The	O
+alignment	O
+in	O
+Figure	O
+1A	O
+displays	O
+the	O
+amino	O
+acid	O
+sequences	O
+encoded	O
+by	O
+the	O
+six	O
+related	O
+ribonuclease	O
+genes	O
+.	O
+
+Murine	B
+eosinophil	O
+-	O
+associated	O
+ribonucleases	O
+-	O
+1	O
+and	O
+-	O
+2	O
+(	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+)	O
+are	O
+the	O
+predicted	O
+amino	O
+acid	O
+sequences	O
+from	O
+two	O
+genes	O
+described	O
+previously	O
+by	O
+Larson	O
+and	O
+colleagues	O
+(	O
+15	O
+)	O
+;	O
+murine	B
+ribonucleases	O
+3	O
+,	O
+4	O
+,	O
+5	O
+and	O
+6	O
+-	O
+pseudogene	O
+(	O
+mR	O
+-	O
+3	O
+,	O
+mR	O
+-	O
+4	O
+,	O
+mR	O
+-	O
+5	O
+and	O
+mR	O
+-	O
+6P	O
+)	O
+,	O
+are	O
+the	O
+predicted	O
+amino	O
+acid	O
+sequences	O
+encoded	O
+by	O
+novel	O
+DNA	O
+
+hEDN	O
+mEAR	O
+-	O
+1	O
+mEAR	O
+-	O
+2	O
+mR	O
+-	O
+3	O
+mR	O
+-	O
+4	O
+mR	O
+-	O
+5	O
+mANG	O
+mPR	O
+56	O
+56	O
+54	O
+60	O
+60	O
+43	O
+53	O
+
+hECP	O
+59	O
+59	O
+57	O
+59	O
+58	O
+49	O
+52	O
+
+hRK6	O
+58	O
+59	O
+59	O
+53	O
+56	O
+49	O
+59	O
+
+hPR	O
+47	O
+48	O
+49	O
+48	O
+57	O
+55	O
+79	O
+
+hR4	O
+50	O
+53	O
+51	O
+52	O
+54	O
+57	O
+66	O
+
+hANG	O
+49	O
+48	O
+51	O
+47	O
+47	O
+80	O
+60	O
+
+Values	O
+are	O
+expressed	O
+as	O
+percent	O
+similarity	O
+between	O
+pairs	O
+of	O
+amino	O
+acid	O
+sequences	O
+as	O
+determined	O
+by	O
+the	O
+BESTFIT	O
+algorithm	O
+of	O
+the	O
+Wisconsin	O
+Genetics	O
+Computer	O
+Group	O
+program	O
+on	O
+-	O
+line	O
+at	O
+the	O
+National	O
+Institutes	O
+of	O
+Health	O
+.	O
+
+Value	O
+representing	O
+the	O
+highest	O
+degree	O
+of	O
+sequence	O
+homology	O
+in	O
+each	O
+row	O
+is	O
+indicated	O
+in	O
+boldface	O
+.	O
+
+Abbreviations	O
+are	O
+as	O
+defined	O
+in	O
+Figures	O
+1	O
+and	O
+2	O
+,	O
+and	O
+also	O
+include	O
+hR4	O
+(	O
+human	B
+ribonuclease	O
+4	O
+,	O
+sw	O
+:	O
+rnl4	O
+_	O
+human	B
+)	O
+,	O
+hANG	O
+(	O
+human	B
+angiogenin	O
+,	O
+M11567	O
+)	O
+,	O
+and	O
+hPR	O
+(	O
+human	B
+pancreatic	O
+ribonuclease	O
+,	O
+X62946	O
+)	O
+.	O
+
+4238	O
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1997	O
+,	O
+Vol	O
+.	O
+
+25	O
+,	O
+No	O
+.	O
+21	O
+fragments	O
+amplified	O
+from	O
+murine	B
+genomic	O
+DNA	O
+.	O
+
+All	O
+five	O
+functional	O
+genes	O
+encode	O
+amino	O
+acid	O
+sequences	O
+with	O
+eight	O
+cysteines	O
+and	O
+appropriately	O
+spaced	O
+catalytic	O
+histidines	O
+and	O
+lysine	O
+that	O
+are	O
+conserved	O
+among	O
+the	O
+members	O
+of	O
+the	O
+RNase	O
+A	O
+superfamily	O
+.	O
+
+The	O
+predicted	O
+coding	O
+sequence	O
+of	O
+the	O
+non	O
+-	O
+functional	O
+pseudogene	O
+(	O
+mR	O
+-	O
+6P	O
+)	O
+includes	O
+two	O
+aberrant	O
+stop	O
+codons	O
+(	O
+positions	O
+19	O
+and	O
+100	O
+)	O
+as	O
+well	O
+as	O
+a	O
+point	O
+mutation	O
+resulting	O
+in	O
+the	O
+destruction	O
+of	O
+the	O
+cysteine	O
+at	O
+position	O
+78	O
+.	O
+
+Each	O
+genomic	O
+fragment	O
+also	O
+encodes	O
+a	O
+28	O
+residue	O
+amino	O
+terminal	O
+signal	O
+sequence	O
+(	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequences	O
+are	O
+displayed	O
+in	O
+order	O
+of	O
+decreasing	O
+similarity	O
+to	O
+mEAR	O
+-	O
+1	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+Genomic	O
+fragments	O
+encoding	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+were	O
+also	O
+detected	O
+.	O
+
+Relationships	O
+among	O
+the	O
+murine	B
+ribonucleases	O
+A	O
+dendrogram	O
+depicting	O
+the	O
+relationships	O
+among	O
+several	O
+of	O
+the	O
+murine	B
+and	O
+human	B
+ribonucleases	O
+is	O
+shown	O
+in	O
+Figure	O
+2A	O
+.	O
+
+The	O
+mEAR	O
+-	O
+1	O
+,	O
+mEAR	O
+-	O
+2	O
+,	O
+and	O
+mR	O
+-	O
+3	O
+sequences	O
+form	O
+a	O
+closely	O
+related	O
+sub	O
+-	O
+group	O
+,	O
+with	O
+only	O
+nine	O
+amino	O
+acid	O
+sequence	O
+differences	O
+noted	O
+between	O
+mEAR	O
+-	O
+2	O
+and	O
+mR	O
+-	O
+3	O
+,	O
+and	O
+12	O
+and	O
+17	O
+between	O
+these	O
+two	O
+and	O
+mEAR	O
+-	O
+1	O
+,	O
+respectively	O
+.	O
+
+The	O
+mR	O
+-	O
+4	O
+,	O
+mR	O
+-	O
+5	O
+,	O
+and	O
+mR	O
+-	O
+6P	O
+sequences	O
+diverge	O
+from	O
+this	O
+subgroup	O
+and	O
+from	O
+one	O
+another	O
+as	O
+well	O
+.	O
+
+These	O
+six	O
+sequences	O
+are	O
+more	O
+closely	O
+related	O
+to	O
+one	O
+another	O
+than	O
+they	O
+are	O
+to	O
+either	O
+murine	B
+pancreatic	O
+ribonuclease	O
+(	O
+mPR	O
+)	O
+or	O
+to	O
+murine	B
+angiogenin	O
+(	O
+mANG	O
+)	O
+or	O
+to	O
+any	O
+of	O
+the	O
+three	O
+human	B
+ribonucleases	O
+shown	O
+(	O
+hEDN	O
+,	O
+hECP	O
+or	O
+hRK6	O
+)	O
+.	O
+
+Isoelectric	O
+points	O
+The	O
+isoelectric	O
+points	O
+of	O
+all	O
+six	O
+related	O
+ribonucleases	O
+range	O
+from	O
+8	O
+<	O
+FFFD	O
+>	O
+11	O
+,	O
+as	O
+is	O
+typical	O
+for	O
+members	O
+of	O
+the	O
+RNase	O
+A	O
+superfamily	O
+(	O
+Fig	O
+.	O
+2B	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+isoelectric	O
+points	O
+within	O
+the	O
+mEAR	O
+-	O
+1	O
+/	O
+mEAR	O
+-	O
+2	O
+/	O
+mR	O
+-	O
+3	O
+subgroup	O
+vary	O
+by	O
+a	O
+full	O
+1	O
+.	O
+0	O
+unit	O
+(	O
+mEAR	O
+-	O
+1	O
+at	O
+9	O
+.	O
+2	O
+to	O
+mEAR	O
+-	O
+2	O
+at	O
+10	O
+.	O
+2	O
+)	O
+in	O
+response	O
+to	O
+only	O
+12	O
+discrepancies	O
+in	O
+amino	O
+acid	O
+sequence	O
+.	O
+
+As	O
+increased	O
+charge	O
+has	O
+been	O
+associated	O
+with	O
+increased	O
+toxicity	O
+in	O
+other	O
+branches	O
+of	O
+the	O
+RNase	O
+A	O
+gene	O
+family	O
+(	O
+18	O
+)	O
+,	O
+this	O
+finding	O
+has	O
+potential	O
+consequences	O
+with	O
+respect	O
+to	O
+the	O
+function	O
+of	O
+these	O
+proteins	O
+(	O
+see	O
+Discussion	O
+)	O
+.	O
+
+Northern	O
+analysis	O
+Tissue	O
+-	O
+specific	O
+expression	O
+of	O
+mRNA	O
+encoding	O
+these	O
+murine	B
+ribonucleases	O
+is	O
+shown	O
+in	O
+Figure	O
+3	O
+.	O
+
+The	O
+probe	O
+complementary	O
+to	O
+all	O
+three	O
+sequences	O
+of	O
+the	O
+mEAR	O
+-	O
+1	O
+/	O
+mEAR	O
+-	O
+2	O
+/	O
+mR	O
+-	O
+3	O
+subgroup	O
+hybridizes	O
+to	O
+an	O
+1	O
+.	O
+4	O
+kb	O
+mRNA	O
+isolated	O
+from	O
+renal	O
+tissue	O
+(	O
+Fig	O
+.	O
+3A	O
+)	O
+.	O
+
+As	O
+the	O
+probe	O
+cannot	O
+distinguish	O
+among	O
+the	O
+three	O
+genes	O
+,	O
+it	O
+is	O
+not	O
+possible	O
+to	O
+conclude	O
+whether	O
+the	O
+band	O
+detected	O
+represents	O
+mRNA	O
+encoding	O
+one	O
+,	O
+two	O
+,	O
+or	O
+all	O
+three	O
+of	O
+the	O
+ribonucleases	O
+of	O
+this	O
+subgroup	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+probe	O
+complementary	O
+to	O
+the	O
+mR	O
+-	O
+5	O
+genomic	O
+fragment	O
+hybridizes	O
+to	O
+two	O
+prominent	O
+mRNA	O
+species	O
+in	O
+hepatic	O
+tissue	O
+,	O
+one	O
+at	O
+1	O
+.	O
+4	O
+kb	O
+,	O
+and	O
+a	O
+second	O
+at	O
+2	O
+.	O
+0	O
+kb	O
+.	O
+
+A	O
+prominent	O
+mRNA	O
+of	O
+1	O
+.	O
+8	O
+kb	O
+was	O
+also	O
+detected	O
+in	O
+mRNA	O
+isolated	O
+from	O
+murine	B
+testicular	O
+tissue	O
+;	O
+fainter	O
+hybridizing	O
+mRNAs	O
+of	O
+varying	O
+size	O
+were	O
+detected	O
+in	O
+lung	O
+and	O
+skeletal	O
+muscle	O
+.	O
+
+The	O
+size	O
+variation	O
+may	O
+represent	O
+differential	O
+splicing	O
+of	O
+the	O
+mR	O
+-	O
+5	O
+-	O
+encoding	O
+mRNA	O
+,	O
+or	O
+may	O
+represent	O
+mRNAs	O
+encoding	O
+one	O
+or	O
+more	O
+as	O
+yet	O
+undiscovered	O
+murine	B
+ribonucleases	O
+that	O
+are	O
+more	O
+closely	O
+related	O
+to	O
+mR	O
+-	O
+5	O
+than	O
+those	O
+whose	O
+sequences	O
+are	O
+reported	O
+here	O
+.	O
+
+Figure	O
+3	O
+.	O
+
+(	O
+A	O
+)	O
+Murine	B
+RNA	O
+probed	O
+with	O
+a	O
+32	O
+bp	O
+oligonucleotide	O
+complementary	O
+to	O
+mEAR	O
+-	O
+1	O
+,	O
+mEAR	O
+-	O
+2	O
+and	O
+mR	O
+-	O
+3	O
+coding	O
+sequences	O
+.	O
+
+Tissue	O
+source	O
+of	O
+each	O
+RNA	O
+is	O
+indicated	O
+above	O
+each	O
+lane	O
+.	O
+
+(	O
+B	O
+)	O
+Same	O
+as	O
+in	O
+(	O
+A	O
+)	O
+,	O
+probed	O
+with	O
+a	O
+32	O
+bp	O
+oligonucleotide	O
+complementary	O
+to	O
+mR	O
+-	O
+5	O
+.	O
+
+(	O
+C	O
+)	O
+Same	O
+as	O
+in	O
+(	O
+A	O
+)	O
+,	O
+probed	O
+with	O
+a	O
+48	O
+bp	O
+oligonucleotide	O
+complementary	O
+to	O
+human	B
+actin	O
+(	O
+16	O
+)	O
+,	O
+demonstrating	O
+relative	O
+loading	O
+of	O
+each	O
+lane	O
+.	O
+
+Relationship	O
+to	O
+human	B
+ribonucleases	O
+The	O
+data	O
+in	O
+Table	O
+1	O
+denote	O
+the	O
+amino	O
+acid	O
+sequence	O
+similarity	O
+between	O
+pairs	O
+of	O
+murine	B
+and	O
+human	B
+ribonucleases	O
+of	O
+the	O
+RNase	O
+A	O
+superfamily	O
+.	O
+
+Overall	O
+,	O
+the	O
+similarities	O
+within	O
+the	O
+identified	O
+cluster	O
+range	O
+from	O
+47	O
+to	O
+60	O
+%	O
+,	O
+with	O
+remarkably	O
+little	O
+variation	O
+among	O
+the	O
+pairs	O
+.	O
+
+Although	O
+the	O
+sequences	O
+of	O
+the	O
+mEAR	O
+-	O
+1	O
+/	O
+mEAR	O
+-	O
+2	O
+/	O
+mR	O
+-	O
+3	O
+subgroup	O
+are	O
+slightly	O
+more	O
+similar	O
+to	O
+ECP	O
+and	O
+RNase	O
+k6	O
+,	O
+and	O
+mR	O
+-	O
+4	O
+and	O
+mR	O
+-	O
+5	O
+,	O
+to	O
+EDN	O
+and	O
+ECP	O
+,	O
+the	O
+orthologous	O
+relationships	O
+of	O
+these	O
+murine	B
+ribonucleases	O
+cannot	O
+be	O
+discerned	O
+from	O
+these	O
+data	O
+.	O
+
+This	O
+stands	O
+in	O
+direct	O
+contrast	O
+to	O
+mPR	O
+and	O
+mANG	O
+,	O
+whose	O
+human	B
+orthologs	O
+can	O
+be	O
+clearly	O
+distinguished	O
+on	O
+the	O
+basis	O
+of	O
+their	O
+amino	O
+acid	O
+sequence	O
+homologies	O
+.	O
+
+DISCUSSION	O
+In	O
+this	O
+work	O
+,	O
+we	O
+have	O
+identified	O
+four	O
+novel	O
+murine	B
+ribonuclease	O
+genes	O
+that	O
+,	O
+together	O
+with	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+defined	O
+by	O
+Larson	O
+and	O
+colleagues	O
+(	O
+15	O
+)	O
+,	O
+form	O
+an	O
+unusual	O
+cluster	O
+within	O
+the	O
+RNase	O
+A	O
+gene	O
+superfamily	O
+.	O
+
+The	O
+six	O
+genes	O
+within	O
+this	O
+cluster	O
+have	O
+varying	O
+amino	O
+acid	O
+sequence	O
+homologies	O
+to	O
+one	O
+another	O
+,	O
+but	O
+are	O
+clearly	O
+more	O
+closely	O
+related	O
+to	O
+one	O
+another	O
+than	O
+to	O
+either	O
+murine	B
+pancreatic	O
+ribonuclease	O
+(	O
+mPR	O
+)	O
+or	O
+angiogenin	O
+(	O
+mANG	O
+)	O
+,	O
+or	O
+to	O
+any	O
+of	O
+the	O
+human	B
+ribonucleases	O
+of	O
+the	O
+RNase	O
+A	O
+family	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+the	O
+`	O
+mR	O
+cluster	O
+'	O
+emerged	O
+via	O
+multiple	O
+duplications	O
+of	O
+a	O
+gene	O
+that	O
+had	O
+already	O
+diverged	O
+from	O
+those	O
+encoding	O
+the	O
+other	O
+murine	B
+ribonucleases	O
+.	O
+
+Although	O
+this	O
+type	O
+of	O
+expansion	O
+is	O
+unusual	O
+in	O
+this	O
+gene	O
+family	O
+,	O
+it	O
+is	O
+actually	O
+not	O
+unique	O
+;	O
+similar	O
+expansion	O
+has	O
+occurred	O
+in	O
+bovine	B
+species	O
+,	O
+with	O
+gene	O
+duplication	O
+resulting	O
+in	O
+the	O
+three	O
+closely	O
+-	O
+related	O
+bovine	B
+pancreatic	O
+,	O
+bovine	B
+brain	O
+(	O
+19	O
+,	O
+20	O
+)	O
+and	O
+bovine	B
+seminal	O
+(	O
+21	O
+)	O
+ribonucleases	O
+.	O
+
+One	O
+interesting	O
+feature	O
+of	O
+the	O
+mR	O
+cluster	O
+is	O
+that	O
+its	O
+relationship	O
+to	O
+any	O
+of	O
+to	O
+the	O
+six	O
+known	O
+human	B
+RNase	O
+A	O
+-	O
+type	O
+genes	O
+cannot	O
+be	O
+
+4239	O
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1997	O
+,	O
+Vol	O
+.	O
+
+25	O
+,	O
+No	O
+.	O
+
+Nucleic	O
+Acids	O
+Research	O
+,	O
+1994	O
+,	O
+Vol	O
+.	O
+
+22	O
+,	O
+No	O
+.	O
+121	O
+determined	O
+from	O
+their	O
+respective	O
+amino	O
+acid	O
+sequence	O
+homologies	O
+.	O
+
+Although	O
+the	O
+amino	O
+acid	O
+sequences	O
+encoded	O
+by	O
+mEAR	O
+-	O
+1	O
+and	O
+mEAR	O
+-	O
+2	O
+match	O
+those	O
+of	O
+tryptic	O
+peptides	O
+derived	O
+from	O
+murine	B
+eosinophil	O
+proteins	O
+(	O
+15	O
+)	O
+,	O
+the	O
+homology	O
+data	O
+do	O
+not	O
+stand	O
+in	O
+overwhelming	O
+support	O
+of	O
+a	O
+unique	O
+relationship	O
+between	O
+any	O
+of	O
+the	O
+mR	O
+cluster	O
+ribonucleases	O
+and	O
+the	O
+human	B
+eosinophil	O
+ribonucleases	O
+EDN	O
+and	O
+ECP	O
+.	O
+
+The	O
+existence	O
+of	O
+an	O
+additional	O
+,	O
+as	O
+yet	O
+unidentified	O
+human	B
+ribonuclease	O
+(	O
+or	O
+ribonucleases	O
+)	O
+more	O
+closely	O
+related	O
+to	O
+those	O
+of	O
+the	O
+mR	O
+cluster	O
+cannot	O
+be	O
+ruled	O
+out	O
+.	O
+
+Perhaps	O
+the	O
+most	O
+important	O
+issue	O
+raised	O
+by	O
+this	O
+work	O
+is	O
+the	O
+question	O
+of	O
+why	O
+so	O
+much	O
+evolutionary	O
+energy	O
+has	O
+been	O
+devoted	O
+to	O
+enlarging	O
+and	O
+diversifying	O
+the	O
+RNase	O
+A	O
+gene	O
+superfamily	O
+.	O
+
+To	O
+date	O
+,	O
+this	O
+superfamily	O
+now	O
+includes	O
+several	O
+distinct	O
+lineages	O
+,	O
+two	O
+species	O
+-	O
+limited	O
+clusters	O
+,	O
+and	O
+the	O
+two	O
+most	O
+rapidly	O
+evolving	O
+functional	O
+coding	O
+sequences	O
+known	O
+among	O
+primates	O
+(	O
+22	O
+)	O
+.	O
+
+The	O
+question	O
+of	O
+evolutionary	O
+energy	O
+takes	O
+on	O
+particular	O
+significance	O
+here	O
+,	O
+where	O
+five	O
+functional	O
+ribonucleases	O
+have	O
+emerged	O
+in	O
+what	O
+appears	O
+to	O
+be	O
+a	O
+remarkably	O
+short	O
+period	O
+of	O
+evolutionary	O
+time	O
+(	O
+15	O
+)	O
+.	O
+
+It	O
+is	O
+conceivable	O
+that	O
+each	O
+of	O
+these	O
+ribonucleases	O
+might	O
+serve	O
+a	O
+unique	O
+but	O
+related	O
+function	O
+.	O
+
+On	O
+this	O
+point	O
+,	O
+a	O
+number	O
+of	O
+studies	O
+have	O
+suggested	O
+a	O
+distinct	O
+role	O
+for	O
+the	O
+human	B
+ribonuclease	O
+ECP	O
+in	O
+eosinophil	O
+-	O
+mediated	O
+host	O
+defense	O
+(	O
+6	O
+,	O
+7	O
+)	O
+;	O
+in	O
+addition	O
+,	O
+we	O
+have	O
+recently	O
+shown	O
+that	O
+eosinophil	O
+ribonucleases	O
+can	O
+inhibit	O
+retroviral	O
+transduction	O
+of	O
+human	B
+target	O
+cells	O
+(	O
+23	O
+)	O
+.	O
+
+The	O
+possibility	O
+that	O
+certain	O
+ribonucleases	O
+have	O
+diverged	O
+to	O
+promote	O
+distinct	O
+and	O
+specific	O
+host	O
+defense	O
+-	O
+related	O
+activities	O
+remains	O
+an	O
+intriguing	O
+hypothesis	O
+.	O
+
+ACKNOWLEDGEMENTS	O
+We	O
+would	O
+like	O
+to	O
+thank	O
+Dr	O
+Jianzhi	O
+Zhang	O
+for	O
+helpful	O
+discussions	O
+,	O
+and	O
+Drs	O
+Harry	O
+L	O
+.	O
+Malech	O
+and	O
+John	O
+I	O
+.	O
+Gallin	O
+for	O
+their	O
+ongoing	O
+suppport	O
+of	O
+the	O
+work	O
+in	O
+our	O
+laboratory	O
+.	O
+
+D	O
+.	O
+B	O
+.	O
+
+is	O
+a	O
+Howard	O
+Hughes	O
+Medical	O
+Institute	O
+-	O
+National	O
+Institutes	O
+of	O
+Health	O
+Research	O
+Scholar	O
+REFERENCES	O
+1	O
+D	O
+'	O
+Alessio	O
+,	O
+G	O
+.	O
+and	O
+Riordan	O
+,	O
+J	O
+.	O
+F	O
+.	O
+
+(	O
+1997	O
+)	O
+In	O
+D	O
+'	O
+Alessio	O
+,	O
+G	O
+.	O
+and	O
+Riordan	O
+,	O
+J	O
+.	O
+F	O
+.	O
+
+(	O
+eds	O
+)	O
+Ribonucleases	O
+:	O
+structure	O
+and	O
+function	O
+.	O
+
+Academic	O
+Press	O
+,	O
+Inc	O
+.	O
+,	O
+New	O
+York	O
+,	O
+NY	O
+.	O
+
+2	O
+Sorrentino	O
+,	O
+S	O
+.	O
+and	O
+Libonati	O
+,	O
+M	O
+.	O
+
+(	O
+1997	O
+)	O
+FEBS	O
+Lett	O
+.	O
+
+404	O
+,	O
+1	O
+<	O
+FFFD	O
+>	O
+5	O
+.	O
+
+21	O
+22	O
+23	O
+24	O
+3	O
+4	O
+5	O
+6	O
+7	O
+8	O
+9	O
+10	O
+11	O
+12	O
+13	O
+14	O
+15	O
+16	O
+17	O
+18	O
+19	O
+20	O
+
+4239	O
+
+Beintema	O
+,	O
+J	O
+.	O
+J	O
+.	O
+,	O
+Breukelman	O
+,	O
+H	O
+.	O
+J	O
+,	O
+Carsana	O
+,	O
+A	O
+.	O
+,	O
+and	O
+Furia	O
+,	O
+A	O
+.	O
+
+(	O
+1997	O
+)	O
+In	O
+D	O
+'	O
+Alessio	O
+,	O
+G	O
+.	O
+and	O
+Riordan	O
+,	O
+J	O
+.	O
+F	O
+.	O
+
+(	O
+eds	O
+)	O
+Ribonucleases	O
+:	O
+structure	O
+and	O
+function	O
+.	O
+
+Academic	O
+Press	O
+,	O
+Inc	O
+.	O
+,	O
+New	O
+York	O
+,	O
+NY	O
+.	O
+
+Confalone	O
+,	O
+E	O
+.	O
+,	O
+Beintema	O
+,	O
+J	O
+.	O
+J	O
+.	O
+,	O
+Sasso	O
+,	O
+M	O
+.	O
+P	O
+.	O
+
+Carsana	O
+,	O
+A	O
+.	O
+,	O
+Palmieria	O
+,	O
+M	O
+.	O
+,	O
+Vento	O
+,	O
+M	O
+.	O
+T	O
+.	O
+and	O
+Furia	O
+A	O
+.	O
+
+(	O
+1995	O
+)	O
+J	O
+.	O
+
+Mol	O
+.	O
+
+Evol	O
+.	O
+
+41	O
+,	O
+850	O
+<	O
+FFFD	O
+>	O
+858	O
+.	O
+
+Futami	O
+,	O
+J	O
+.	O
+,	O
+Tsushima	O
+,	O
+Y	O
+.	O
+,	O
+Murato	O
+,	O
+U	O
+,	O
+Tada	O
+,	O
+H	O
+.	O
+,	O
+Sasaki	O
+,	O
+J	O
+.	O
+,	O
+Seno	O
+,	O
+M	O
+.	O
+,	O
+and	O
+Yamada	O
+,	O
+H	O
+.	O
+
+(	O
+1997	O
+)	O
+DNA	O
+Cell	O
+Biol	O
+.	O
+
+16	O
+,	O
+413	O
+<	O
+FFFD	O
+>	O
+419	O
+.	O
+
+Ackerman	O
+,	O
+S	O
+.	O
+J	O
+.	O
+
+(	O
+1993	O
+)	O
+In	O
+Makino	O
+,	O
+S	O
+.	O
+and	O
+Fukuda	O
+,	O
+T	O
+.	O
+
+(	O
+eds	O
+)	O
+Eosinophils	O
+:	O
+biological	O
+and	O
+clinical	O
+aspects	O
+.	O
+
+CRC	O
+Press	O
+,	O
+Inc	O
+.	O
+,	O
+Boca	O
+Raton	O
+,	O
+FL	O
+Spry	O
+,	O
+C	O
+.	O
+J	O
+.	O
+F	O
+.	O
+
+(	O
+1988	O
+)	O
+Eosinophils	O
+:	O
+a	O
+comprehensive	O
+review	O
+and	O
+guide	O
+to	O
+the	O
+scientific	O
+and	O
+medical	O
+literature	O
+.	O
+
+Oxford	O
+University	O
+Press	O
+,	O
+Oxford	O
+,	O
+UK	O
+.	O
+
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+(	O
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+10	O
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+,	O
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+,	O
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+,	O
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+,	O
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+(	O
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+
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+Cu	O
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+,	O
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+
+Although	O
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+-	O
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+-	O
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+the	O
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+42	O
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+.	O
+
+Environmental	O
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+Perspectives	O
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+.	O
+
+65	O
+,	O
+pp	O
+.	O
+
+71	O
+-	O
+75	O
+,	O
+1986	O
+
+Physiological	O
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+Chemical	O
+
+Characterization	O
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+Cyanobacterial	O
+Metallothioneins	O
+
+by	O
+Robert	O
+W	O
+.	O
+Olafson	O
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+
+Techniques	O
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+been	O
+developed	O
+for	O
+detection	O
+,	O
+quantitation	O
+,	O
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+metallothioneins	O
+(	O
+MTs	O
+)	O
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+species	O
+.	O
+
+These	O
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+-	O
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+high	O
+-	O
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+(	O
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+)	O
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+picomole	O
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+these	O
+high	O
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+content	O
+proteins	O
+.	O
+
+The	O
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+Cd	O
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+
+Cu	O
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+
+Exposure	O
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+induction	O
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+MT	O
+synthesis	O
+and	O
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+of	O
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+.	O
+
+Amino	O
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+analysis	O
+and	O
+N	O
+-	O
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+indicated	O
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+,	O
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+
+Although	O
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+-	O
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+,	O
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+.	O
+
+Introduction	O
+
+Metallothioneins	O
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+isolated	O
+and	O
+characterized	O
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+variety	O
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+eukaryotic	O
+organisms	O
+(	O
+1	O
+)	O
+and	O
+shown	O
+to	O
+be	O
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+/	O
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+(	O
+2	O
+-	O
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+)	O
+.	O
+
+These	O
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+in	O
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+-	O
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+cluster	O
+arrangements	O
+,	O
+the	O
+structures	O
+of	O
+which	O
+have	O
+been	O
+recently	O
+
+investigated	O
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+-	O
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+6	O
+)	O
+.	O
+
+Although	O
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+(	O
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+)	O
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+,	O
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+this	O
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+high	O
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+-	O
+binding	O
+protein	O
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+.	O
+
+We	O
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+reported	O
+the	O
+presence	O
+of	O
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+(	O
+7	O
+,	O
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+)	O
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+primary	O
+sequence	O
+evidence	O
+substantiating	O
+these	O
+data	O
+.	O
+
+This	O
+manuscript	O
+is	O
+intended	O
+to	O
+summarize	O
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+present	O
+state	O
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+,	O
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+such	O
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+.	O
+
+Analytical	O
+Procedure	O
+
+In	O
+order	O
+to	O
+facilitate	O
+rapid	O
+detection	O
+,	O
+isolation	O
+,	O
+and	O
+quantitation	O
+of	O
+MT	O
+from	O
+various	O
+sources	O
+,	O
+we	O
+have	O
+routinely	O
+employed	O
+a	O
+differential	O
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+polarographic	O
+tech	O
+
+*	O
+Department	O
+of	O
+Biochemistry	O
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+Microbiology	O
+,	O
+University	O
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+,	O
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+,	O
+British	O
+Columbia	O
+V8W	O
+2Y2	O
+,	O
+Canada	O
+.	O
+
+nique	O
+first	O
+described	O
+by	O
+Brdicka	O
+(	O
+9	O
+-	O
+11	O
+)	O
+.	O
+
+This	O
+procedure	O
+avoids	O
+use	O
+of	O
+radioisotopes	O
+and	O
+circumvents	O
+problems	O
+such	O
+as	O
+species	O
+specificity	O
+and	O
+metal	O
+stoichiometric	O
+assumptions	O
+associated	O
+with	O
+radioimmunoassays	O
+and	O
+metal	O
+binding	O
+assays	O
+.	O
+
+Figure	O
+1	O
+shows	O
+a	O
+typical	O
+polarographic	O
+wave	O
+for	O
+MT	O
+using	O
+the	O
+Brdicka	O
+procedure	O
+.	O
+
+Measurement	O
+of	O
+the	O
+wave	O
+height	O
+can	O
+be	O
+performed	O
+from	O
+either	O
+the	O
+
+0	O
+.	O
+20	O
+
+glJ	O
+MT	O
+-	O
+1	O
+
+O	O
+0	O
+.	O
+15	O
+
+E	O
+
+0	O
+0	O
+.	O
+10	O
+0	O
+
+E	O
+0	O
+.	O
+05	O
+_	O
+_	O
+
+-	O
+1	O
+.	O
+35	O
+-	O
+1	O
+.	O
+45	O
+-	O
+1	O
+.	O
+55	O
+-	O
+1	O
+.	O
+65	O
+
+V	O
+vs	O
+Agt	O
+/	O
+AgC1	O
+
+FIGURE	O
+1	O
+.	O
+
+Differential	O
+pulse	O
+polarographic	O
+wave	O
+for	O
+murine	B
+MT	O
+-	O
+1	O
+.	O
+
+Wave	O
+heights	O
+were	O
+calculated	O
+from	O
+the	O
+broken	O
+tangent	O
+line	O
+between	O
+minima	O
+rather	O
+than	O
+the	O
+supporting	O
+electrolyte	O
+baseline	O
+at	O
+the	O
+bottom	O
+of	O
+the	O
+figure	O
+.	O
+
+R	O
+.	O
+
+W	O
+OLAFSON	O
+
+supporting	O
+electrolyte	O
+baseline	O
+or	O
+a	O
+tangent	O
+to	O
+the	O
+minima	O
+as	O
+shown	O
+in	O
+the	O
+preceding	O
+figure	O
+.	O
+
+In	O
+the	O
+cobalt	O
+hexaminechloride	O
+supporting	O
+electrolyte	O
+,	O
+the	O
+half	O
+-	O
+wave	O
+potential	O
+for	O
+all	O
+MTs	O
+studied	O
+to	O
+date	O
+is	O
+approximately	O
+-	O
+1	O
+.	O
+45	O
+V	O
+versus	O
+a	O
+Ag	O
+/	O
+AgCl	O
+reference	O
+electrode	O
+.	O
+
+This	O
+electrochemical	O
+reaction	O
+results	O
+in	O
+highly	O
+reproducible	O
+and	O
+linear	O
+current	O
+responses	O
+which	O
+can	O
+be	O
+used	O
+with	O
+samples	O
+containing	O
+picomole	O
+levels	O
+of	O
+MT	O
+(	O
+Fig	O
+.	O
+2	O
+)	O
+.	O
+
+Since	O
+this	O
+is	O
+an	O
+exceedingly	O
+sensitive	O
+instrument	O
+,	O
+attention	O
+to	O
+detail	O
+is	O
+particularly	O
+important	O
+for	O
+successful	O
+use	O
+of	O
+the	O
+Brdicka	O
+procedure	O
+(	O
+11	O
+)	O
+.	O
+
+Routine	O
+use	O
+of	O
+a	O
+reference	O
+standard	O
+MT	O
+is	O
+highly	O
+recommended	O
+to	O
+compensate	O
+for	O
+small	O
+day	O
+-	O
+today	O
+variations	O
+in	O
+response	O
+.	O
+
+For	O
+absolute	O
+values	O
+,	O
+standards	O
+must	O
+be	O
+identical	O
+to	O
+the	O
+species	O
+of	O
+protein	O
+quantitated	O
+;	O
+otherwise	O
+commercially	O
+available	O
+standard	O
+is	O
+adequate	O
+.	O
+
+Although	O
+certain	O
+tissues	O
+and	O
+cellular	O
+types	O
+can	O
+be	O
+shown	O
+to	O
+have	O
+no	O
+other	O
+polarographically	O
+active	O
+material	O
+other	O
+than	O
+MT	O
+,	O
+with	O
+samples	O
+from	O
+new	O
+species	O
+,	O
+it	O
+is	O
+necessary	O
+to	O
+evaluate	O
+this	O
+potential	O
+problem	O
+by	O
+gelperneation	O
+chromatography	O
+and	O
+,	O
+if	O
+necessary	O
+,	O
+take	O
+steps	O
+to	O
+remove	O
+contaminants	O
+before	O
+assaying	O
+.	O
+
+In	O
+most	O
+cases	O
+,	O
+
+0	O
+
+E	O
+i	O
+
+m	O
+0	O
+
+0	O
+E	O
+
+0	O
+.	O
+31	O
+
+0	O
+.	O
+11	O
+
+O	O
+0	O
+.	O
+1	O
+0	O
+.	O
+3	O
+0	O
+.	O
+5	O
+
+MT	O
+(	O
+nanomoles	O
+)	O
+
+FIGURE	O
+2	O
+.	O
+
+Standard	O
+curve	O
+for	O
+polarographic	O
+determination	O
+of	O
+me	O
+
+tallothionein	O
+.	O
+
+FIGURE	O
+3	O
+.	O
+
+Cyclic	O
+voltamogram	O
+obtained	O
+by	O
+equilibration	O
+at	O
+-	O
+1	O
+.	O
+0	O
+V	O
+
+for	O
+4	O
+min	O
+followed	O
+by	O
+cyclic	O
+scanning	O
+to	O
+OV	O
+and	O
+-	O
+1	O
+.	O
+4	O
+V	O
+at	O
+a	O
+scan	O
+rate	O
+of	O
+200	O
+mV	O
+/	O
+sec	O
+with	O
+a	O
+PAR	O
+Model	O
+303	O
+static	O
+mercury	O
+drop	O
+electrode	O
+in	O
+the	O
+hanging	O
+drop	O
+mode	O
+.	O
+
+The	O
+mercury	O
+drop	O
+electrode	O
+was	O
+set	O
+in	O
+the	O
+large	O
+drop	O
+position	O
+producing	O
+a	O
+drop	O
+of	O
+0	O
+.	O
+0226	O
+cm3	O
+.	O
+
+The	O
+supporting	O
+electrolyte	O
+was	O
+20	O
+mM	O
+HEPES	O
+buffer	O
+,	O
+pH	O
+7	O
+.	O
+3	O
+.	O
+
+The	O
+dotted	O
+line	O
+is	O
+the	O
+equilibrium	O
+trace	O
+.	O
+
+Adapted	O
+Olafson	O
+and	O
+Sim	O
+(	O
+10	O
+)	O
+.	O
+
+this	O
+is	O
+easily	O
+managed	O
+by	O
+heat	O
+denaturation	O
+,	O
+if	O
+care	O
+is	O
+taken	O
+to	O
+assess	O
+the	O
+degree	O
+of	O
+MT	O
+losses	O
+due	O
+to	O
+coprecipitation	O
+.	O
+
+Such	O
+losses	O
+later	O
+can	O
+usually	O
+be	O
+minimized	O
+to	O
+less	O
+than	O
+10	O
+%	O
+by	O
+adjustment	O
+of	O
+the	O
+tissue	O
+homogenate	O
+density	O
+prior	O
+to	O
+denaturation	O
+.	O
+
+It	O
+should	O
+be	O
+indicated	O
+that	O
+additional	O
+utility	O
+can	O
+be	O
+found	O
+with	O
+a	O
+polarographic	O
+analyzer	O
+beyond	O
+application	O
+of	O
+the	O
+Brdicka	O
+procedure	O
+.	O
+
+For	O
+example	O
+,	O
+metal	O
+levels	O
+can	O
+be	O
+readily	O
+determined	O
+by	O
+using	O
+differential	O
+pulse	O
+or	O
+anodic	O
+stripping	O
+voltametry	O
+procedures	O
+(	O
+10	O
+)	O
+,	O
+while	O
+Figure	O
+3	O
+shows	O
+a	O
+cyclic	O
+voltamogram	O
+of	O
+bacterial	O
+MT	O
+.	O
+
+The	O
+latter	O
+technique	O
+is	O
+potentially	O
+useful	O
+in	O
+assessing	O
+metal	O
+speciation	O
+and	O
+integrity	O
+of	O
+the	O
+protein	O
+tertiary	O
+structure	O
+near	O
+metal	O
+clusters	O
+,	O
+particularly	O
+after	O
+metal	O
+reconstitution	O
+studies	O
+.	O
+
+E	O
+
+'	O
+C2A	O
+-	O
+E	O
+24	O
+
+0	O
+30	O
+40	O
+E0	O
+
+*	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+
+o	O
+C	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+C	O
+
+Fraction	O
+Number	O
+(	O
+18ml	O
+)	O
+
+FIGURE	O
+4	O
+.	O
+
+Sephadex	O
+G	O
+-	O
+75	O
+chromatography	O
+profile	O
+of	O
+bacterial	O
+cell	O
+
+lysate	O
+applied	O
+to	O
+a	O
+5	O
+x	O
+100	O
+cm	O
+column	O
+and	O
+eluted	O
+with	O
+10	O
+mM	O
+anunoium	O
+bicarbonate	O
+,	O
+5	O
+mM	O
+mercaptoethanol	O
+(	O
+7	O
+)	O
+.	O
+
+Elution	O
+Time	O
+(	O
+min	O
+)	O
+
+FIGURE	O
+5	O
+.	O
+
+Reverse	O
+-	O
+phase	O
+high	O
+-	O
+performance	O
+chromatography	O
+profile	O
+
+of	O
+Sephadex	O
+G	O
+-	O
+75	O
+fractionated	O
+bacterial	O
+MT	O
+.	O
+
+The	O
+300	O
+A	O
+pore	O
+size	O
+propyl	O
+column	O
+was	O
+eluted	O
+with	O
+20	O
+mM	O
+triethylamine	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+0	O
+,	O
+by	O
+using	O
+an	O
+acetonitrile	O
+organic	O
+modifier	O
+(	O
+phase	O
+B	O
+)	O
+.	O
+
+Column	O
+effluent	O
+was	O
+monitored	O
+at	O
+250	O
+nm	O
+with	O
+a	O
+sensitivity	O
+of	O
+1	O
+.	O
+0	O
+AUFS	O
+(	O
+12	O
+)	O
+.	O
+
+72	O
+
+CYANOBACTERIAL	B
+METALLOTHIONEINS	O
+
+Isolation	O
+of	O
+Cyanobacterial	O
+MT	O
+
+Synechococcus	B
+strain	I
+Tx	I
+-	I
+20	I
+cyanobacteria	O
+were	O
+maintained	O
+in	O
+axenic	O
+culture	O
+on	O
+BG	O
+-	O
+11	O
+medium	O
+(	O
+7	O
+)	O
+and	O
+harvested	O
+from	O
+aerated	O
+20	O
+L	O
+cultures	O
+grown	O
+at	O
+280C	O
+under	O
+fluorescent	O
+light	O
+.	O
+
+Cells	O
+were	O
+broken	O
+in	O
+a	O
+French	O
+pressure	O
+cell	O
+at	O
+0	O
+?	O
+C	O
+in	O
+0	O
+.	O
+5	O
+M	O
+Tris	O
+-	O
+HCI	O
+,	O
+pH	O
+8	O
+.	O
+6	O
+,	O
+and	O
+the	O
+lysate	O
+exposed	O
+to	O
+10	O
+,	O
+uCi	O
+of	O
+109CdCl	O
+.	O
+
+The	O
+40	O
+,	O
+000g	O
+supernatant	O
+was	O
+applied	O
+to	O
+a	O
+Sephadex	O
+G	O
+-	O
+75	O
+column	O
+developed	O
+with	O
+10	O
+mM	O
+ammonium	O
+bicarbonate	O
+and	O
+5	O
+mM	O
+mercaptoethanol	O
+resulting	O
+in	O
+the	O
+profile	O
+shown	O
+in	O
+Figure	O
+4	O
+.	O
+
+Polarographic	O
+activity	O
+and	O
+radionuclide	O
+binding	O
+were	O
+coincident	O
+with	O
+a	O
+10	O
+,	O
+000	O
+MW	O
+ultraviolet	O
+absorbing	O
+fraction	O
+.	O
+
+Further	O
+purification	O
+of	O
+this	O
+material	O
+could	O
+be	O
+undertaken	O
+by	O
+DEAE	O
+-	O
+cellulose	O
+chromatography	O
+or	O
+isoelectric	O
+focusing	O
+but	O
+maximum	O
+resolution	O
+of	O
+isoproteins	O
+was	O
+best	O
+attained	O
+by	O
+reverse	O
+-	O
+phase	O
+high	O
+-	O
+performance	O
+liquid	O
+chromatogra	O
+
+0	O
+5	O
+
+DAYS	O
+
+I0	O
+
+5	O
+
+phy	O
+.	O
+
+Figure	O
+5	O
+shows	O
+such	O
+a	O
+separation	O
+performed	O
+on	O
+a	O
+300	O
+A	O
+pore	O
+size	O
+C	O
+-	O
+3	O
+column	O
+(	O
+Beckman	O
+Instruments	O
+)	O
+.	O
+
+Four	O
+baseline	O
+resolved	O
+MT	O
+peaks	O
+appear	O
+between	O
+40	O
+and	O
+70	O
+min	O
+.	O
+
+Peaks	O
+eluting	O
+at	O
+80	O
+min	O
+contain	O
+at	O
+least	O
+four	O
+additional	O
+MT	O
+components	O
+resolvable	O
+by	O
+adjustment	O
+of	O
+the	O
+applied	O
+organic	O
+modifier	O
+ramp	O
+.	O
+
+Preliminary	O
+evidence	O
+indicates	O
+that	O
+these	O
+isoproteins	O
+are	O
+microheterogeneous	O
+with	O
+respect	O
+to	O
+both	O
+amino	O
+acid	O
+composition	O
+and	O
+metal	O
+speciation	O
+resulting	O
+in	O
+the	O
+observed	O
+reverse	O
+-	O
+phase	O
+separation	O
+.	O
+
+Physiological	O
+Characteristics	O
+of	O
+Cyanobacterial	O
+MT	O
+
+Using	O
+the	O
+Brdicka	O
+polarographic	O
+procedure	O
+,	O
+it	O
+is	O
+possible	O
+to	O
+measure	O
+basal	O
+MT	O
+levels	O
+in	O
+Synechococcus	O
+strain	O
+
+5	O
+
+DAYS	O
+
+10	O
+
+15	O
+
+FIGURE	O
+6	O
+.	O
+
+Cell	O
+numbers	O
+and	O
+MT	O
+concentrations	O
+as	O
+a	O
+function	O
+of	O
+time	O
+after	O
+inoculation	O
+of	O
+wild	O
+-	O
+type	O
+cyanobacteria	O
+in	O
+the	O
+presence	O
+and	O
+absence	O
+
+of	O
+(	O
+A	O
+)	O
+22	O
+.	O
+5	O
+,	O
+uM	O
+CdCl2	O
+;	O
+(	O
+B	O
+)	O
+control	O
+;	O
+(	O
+C	O
+)	O
+50	O
+,	O
+uM	O
+ZnSO4	O
+;	O
+(	O
+D	O
+)	O
+50	O
+,	O
+uM	O
+CuCl2	O
+(	O
+8	O
+)	O
+.	O
+
+73	O
+
+74	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+R	O
+.	O
+
+W	O
+OLAFSON	O
+
+Table	O
+1	O
+.	O
+
+Amino	O
+acid	O
+compositions	O
+of	O
+cyanobacterial	O
+
+metallothioneins	O
+compared	O
+with	O
+eukaryotic	O
+metallothioneins	O
+.	O
+
+Nearest	O
+integer	O
+residues	O
+per	O
+molecule	O
+Human	B
+(	O
+MT	O
+-	O
+2	O
+)	O
+Crab	O
+(	O
+MT	O
+-	O
+2	O
+)	O
+Tx	O
+-	O
+20t	O
+CysA	O
+20	O
+18	O
+9	O
+.	O
+5	O
+Asx	O
+4	O
+6	O
+5	O
+.	O
+7	O
+Thr	O
+2	O
+3	O
+4	O
+.	O
+8	O
+Ser	O
+8	O
+5	O
+3	O
+.	O
+8	O
+Glx	O
+2	O
+5	O
+2	O
+.	O
+0	O
+Gly	O
+5	O
+3	O
+8	O
+.	O
+0	O
+Ala	O
+7	O
+1	O
+4	O
+.	O
+0	O
+Val	O
+1	O
+-	O
+2	O
+.	O
+3	O
+Met	O
+1	O
+-	O
+
+Ile	O
+1	O
+-	O
+1	O
+.	O
+1	O
+
+Leu	O
+Tyr	O
+Phe	O
+His	O
+Lys	O
+Arg	O
+Pro	O
+
+8	O
+2	O
+
+8	O
+2	O
+6	O
+
+2	O
+.	O
+9	O
+2	O
+.	O
+3	O
+
+2	O
+.	O
+8	O
+2	O
+.	O
+6	O
+1	O
+.	O
+0	O
+1	O
+.	O
+9	O
+
+RRIMP	O
+NI	O
+cells	O
+cultured	O
+in	O
+the	O
+absence	O
+of	O
+added	O
+metal	O
+,	O
+as	O
+shown	O
+in	O
+Figure	O
+6B	O
+(	O
+8	O
+)	O
+.	O
+
+Comparison	O
+with	O
+cultures	O
+exposed	O
+to	O
+cadmium	O
+chloride	O
+(	O
+Fig	O
+.	O
+6A	O
+)	O
+or	O
+zinc	O
+sulfate	O
+(	O
+Fig	O
+.	O
+6C	O
+)	O
+showed	O
+that	O
+introduction	O
+of	O
+metal	O
+salts	O
+resulted	O
+in	O
+a	O
+growth	O
+lag	O
+and	O
+that	O
+resumption	O
+of	O
+growth	O
+occurred	O
+coincident	O
+with	O
+an	O
+increase	O
+in	O
+cellular	O
+levels	O
+of	O
+MT	O
+.	O
+
+In	O
+addition	O
+,	O
+it	O
+should	O
+be	O
+noted	O
+that	O
+,	O
+like	O
+mammalian	O
+MT	O
+,	O
+cadmium	O
+appears	O
+to	O
+be	O
+a	O
+more	O
+potent	O
+inducer	O
+than	O
+zinc	O
+.	O
+
+Twice	O
+as	O
+much	O
+cadmium	O
+-	O
+thionein	O
+was	O
+synthesized	O
+on	O
+exposure	O
+to	O
+half	O
+as	O
+much	O
+metal	O
+as	O
+was	O
+used	O
+in	O
+the	O
+zinc	O
+induction	O
+experiment	O
+.	O
+
+A	O
+further	O
+interesting	O
+finding	O
+was	O
+that	O
+copper	O
+exposure	O
+resulted	O
+in	O
+an	O
+even	O
+greater	O
+growth	O
+lag	O
+than	O
+observed	O
+with	O
+cadmium	O
+,	O
+but	O
+on	O
+resumption	O
+of	O
+growth	O
+in	O
+the	O
+presence	O
+copper	O
+,	O
+MT	O
+synthesis	O
+was	O
+not	O
+noted	O
+(	O
+Fig	O
+.	O
+6D	O
+)	O
+.	O
+
+Recent	O
+results	O
+suggest	O
+that	O
+this	O
+copper	O
+resistance	O
+is	O
+manifest	O
+via	O
+a	O
+membrane	O
+exclusion	O
+mechanism	O
+(	O
+unpublished	O
+results	O
+)	O
+.	O
+
+HOURS	O
+
+FIGURE	O
+7	O
+.	O
+
+Inhibition	O
+of	O
+cadmium	O
+induced	O
+synthesis	O
+by	O
+actinomycin	O
+
+D	O
+(	O
+hatched	O
+bar	O
+)	O
+and	O
+chloramphenicol	O
+(	O
+solid	O
+bar	O
+)	O
+.	O
+
+Control	O
+cells	O
+are	O
+shown	O
+by	O
+unmarked	O
+bars	O
+.	O
+
+In	O
+order	O
+that	O
+the	O
+level	O
+of	O
+regulation	O
+of	O
+metal	O
+induction	O
+be	O
+determined	O
+for	O
+cyanobacteria	O
+,	O
+logarithmically	O
+growing	O
+cultures	O
+were	O
+exposed	O
+to	O
+cadmium	O
+and	O
+MT	O
+concentrations	O
+measured	O
+at	O
+several	O
+time	O
+intervals	O
+thereafter	O
+.	O
+
+Two	O
+cultures	O
+were	O
+exposed	O
+to	O
+either	O
+chloramphenicol	O
+or	O
+actinomycin	O
+D	O
+30	O
+min	O
+prior	O
+to	O
+introduction	O
+of	O
+metal	O
+,	O
+while	O
+a	O
+third	O
+culture	O
+was	O
+used	O
+as	O
+a	O
+control	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+experiment	O
+are	O
+shown	O
+in	O
+Figure	O
+7	O
+and	O
+indicate	O
+induction	O
+at	O
+the	O
+level	O
+of	O
+transcription	O
+,	O
+as	O
+was	O
+found	O
+in	O
+eukaryotic	O
+organisms	O
+.	O
+
+The	O
+assumption	O
+at	O
+this	O
+stage	O
+in	O
+these	O
+investigations	O
+was	O
+that	O
+the	O
+growth	O
+lag	O
+observed	O
+in	O
+cultures	O
+exposed	O
+to	O
+
+Table	O
+2	O
+.	O
+
+Amino	O
+acid	O
+sequence	O
+analysis	O
+.	O
+
+Amino	O
+acid	O
+
+1	O
+10	O
+20	O
+30	O
+Cyanobacteria	O
+T	O
+S	O
+T	O
+T	O
+L	O
+V	O
+K	O
+C	O
+A	O
+C	O
+E	O
+P	O
+C	O
+L	O
+C	O
+N	O
+V	O
+D	O
+P	O
+S	O
+K	O
+A	O
+I	O
+D	O
+R	O
+N	O
+G	O
+L	O
+Y	O
+Y	O
+Scylla	O
+P	O
+DP	O
+C	O
+C	O
+NDK	O
+C	O
+DC	O
+K	O
+EG	O
+EC	O
+KT	O
+GC	O
+K	O
+CT	O
+S	O
+C	O
+Human	B
+Ac	O
+MD	O
+P	O
+NC	O
+S	O
+C	O
+AA	O
+G	O
+DS	O
+CT	O
+C	O
+AG	O
+S	O
+C	O
+KC	O
+KE	O
+C	O
+KC	O
+T	O
+S	O
+C	O
+
+Neurospora	O
+
+G	O
+D	O
+C	O
+G	O
+C	O
+S	O
+G	O
+A	O
+S	O
+S	O
+C	O
+N	O
+C	O
+G	O
+S	O
+G	O
+C	O
+S	O
+C	O
+S	O
+N	O
+
+C	O
+G	O
+S	O
+K	O
+
+Table	O
+2	O
+.	O
+
+Continued	O
+.	O
+
+Amino	O
+acid	O
+
+40	O
+50	O
+60	O
+C	O
+C	O
+EAC	O
+A	O
+H	O
+GHT	O
+G	O
+G	O
+
+R	O
+CP	O
+PC	O
+EQ	O
+C	O
+S	O
+SGC	O
+K	O
+CA	O
+NK	O
+E	O
+DC	O
+RK	O
+TC	O
+SK	O
+PC	O
+SCC	O
+P	O
+K	O
+K	O
+SCC	O
+S	O
+CCP	O
+V	O
+GC	O
+A	O
+KCA	O
+Q	O
+BC	O
+I	O
+C	O
+K	O
+GA	O
+SDK	O
+C	O
+S	O
+CC	O
+A	O
+
+74	O
+
+I	O
+
+II	O
+
+I	O
+I	O
+
+CYANOBACTERIAL	B
+METALLOTHIONEINS	O
+75	O
+
+cadmium	O
+or	O
+zinc	O
+was	O
+due	O
+to	O
+a	O
+rather	O
+protracted	O
+time	O
+of	O
+MT	O
+induction	O
+,	O
+perhaps	O
+associated	O
+with	O
+toxic	O
+burden	O
+.	O
+
+If	O
+the	O
+above	O
+cadmium	O
+-	O
+resistant	O
+cells	O
+were	O
+transferred	O
+into	O
+fresh	O
+media	O
+in	O
+the	O
+absence	O
+of	O
+cadmium	O
+and	O
+allowed	O
+to	O
+grow	O
+up	O
+between	O
+three	O
+successive	O
+transfers	O
+,	O
+levels	O
+of	O
+MT	O
+dropped	O
+to	O
+near	O
+basal	O
+values	O
+as	O
+synthesis	O
+was	O
+repressed	O
+in	O
+the	O
+absence	O
+of	O
+metal	O
+.	O
+
+However	O
+,	O
+when	O
+these	O
+cells	O
+were	O
+now	O
+transferred	O
+into	O
+cadmium	O
+-	O
+containing	O
+media	O
+,	O
+instead	O
+of	O
+the	O
+predicted	O
+growth	O
+lag	O
+,	O
+they	O
+grew	O
+immediately	O
+.	O
+
+Thus	O
+,	O
+these	O
+cells	O
+were	O
+truly	O
+cadmium	O
+resistant	O
+.	O
+
+Since	O
+50	O
+tubes	O
+of	O
+wild	O
+-	O
+type	O
+cells	O
+at	O
+a	O
+dilution	O
+of	O
+104	O
+grew	O
+,	O
+after	O
+the	O
+usual	O
+lag	O
+on	O
+exposure	O
+to	O
+cadmium	O
+-	O
+containing	O
+media	O
+,	O
+the	O
+acquisition	O
+of	O
+cadmium	O
+resistance	O
+in	O
+this	O
+strain	O
+of	O
+Synechococcus	O
+was	O
+therefore	O
+considered	O
+unlikely	O
+to	O
+be	O
+related	O
+to	O
+a	O
+chromosomal	O
+mutational	O
+event	O
+.	O
+
+Such	O
+a	O
+mutation	O
+frequency	O
+would	O
+be	O
+unreasonably	O
+high	O
+.	O
+
+Although	O
+no	O
+direct	O
+evidence	O
+exists	O
+at	O
+this	O
+time	O
+,	O
+this	O
+metal	O
+resistance	O
+phenomenon	O
+is	O
+best	O
+explained	O
+by	O
+the	O
+amplification	O
+of	O
+an	O
+extrachromosomal	O
+gene	O
+,	O
+especially	O
+since	O
+this	O
+strain	O
+is	O
+known	O
+to	O
+have	O
+plasmids	O
+.	O
+
+Structure	O
+of	O
+Cyanobacterial	O
+MT	O
+
+The	O
+structural	O
+determination	O
+of	O
+cyanobacterial	B
+MT	O
+is	O
+not	O
+yet	O
+complete	O
+,	O
+although	O
+a	O
+substantial	O
+amount	O
+of	O
+information	O
+is	O
+now	O
+known	O
+.	O
+
+For	O
+example	O
+,	O
+Table	O
+1	O
+compares	O
+the	O
+amino	O
+acid	O
+composition	O
+of	O
+a	O
+Synechococcus	B
+TX	I
+-	I
+20	I
+isoprotein	O
+with	O
+two	O
+eukaryotic	O
+MTs	O
+.	O
+
+These	O
+data	O
+indicate	O
+that	O
+the	O
+bacterial	O
+form	O
+is	O
+unique	O
+.	O
+
+While	O
+cysteine	O
+was	O
+still	O
+the	O
+predominant	O
+amino	O
+acid	O
+in	O
+this	O
+protein	O
+,	O
+levels	O
+of	O
+the	O
+amino	O
+acid	O
+were	O
+half	O
+that	O
+seen	O
+in	O
+the	O
+eukaryotes	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+bacterial	O
+protein	O
+had	O
+two	O
+tyrosines	O
+,	O
+three	O
+histidines	O
+,	O
+and	O
+five	O
+long	O
+-	O
+chain	O
+aliphatics	O
+-	O
+all	O
+residues	O
+rarely	O
+found	O
+in	O
+eukaryotic	O
+MTs	O
+.	O
+
+Thus	O
+,	O
+the	O
+amino	O
+acid	O
+composition	O
+indicates	O
+that	O
+prokaryotic	O
+MTs	O
+are	O
+not	O
+as	O
+structurally	O
+homologous	O
+with	O
+eukaryotes	O
+as	O
+they	O
+are	O
+physiologically	O
+homologous	O
+.	O
+
+This	O
+was	O
+further	O
+exemplified	O
+on	O
+amino	O
+terminal	O
+amino	O
+acid	O
+sequence	O
+analysis	O
+(	O
+12	O
+)	O
+.	O
+
+With	O
+the	O
+exception	O
+of	O
+the	O
+typical	O
+Cys	O
+-	O
+X	O
+-	O
+Cys	O
+sequences	O
+,	O
+the	O
+first	O
+42	O
+residues	O
+of	O
+the	O
+prokaryotic	O
+MT	O
+were	O
+essentially	O
+without	O
+homology	O
+on	O
+comparison	O
+with	O
+the	O
+crab	B
+(	O
+Scylla	B
+)	O
+,	O
+human	B
+,	O
+or	O
+Neurospora	B
+crassa	I
+MTs	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Of	O
+the	O
+above	O
+-	O
+mentioned	O
+uncommon	O
+MT	O
+residues	O
+,	O
+two	O
+tyrosines	O
+were	O
+found	O
+together	O
+in	O
+positions	O
+29	O
+and	O
+30	O
+,	O
+all	O
+five	O
+of	O
+the	O
+long	O
+-	O
+chain	O
+aliphatic	O
+amino	O
+acids	O
+were	O
+located	O
+in	O
+the	O
+first	O
+28	O
+residues	O
+,	O
+and	O
+two	O
+histidines	O
+were	O
+situated	O
+at	O
+positions	O
+37	O
+and	O
+39	O
+.	O
+
+Perhaps	O
+of	O
+greater	O
+interest	O
+was	O
+the	O
+complete	O
+lack	O
+of	O
+association	O
+of	O
+basic	O
+residues	O
+or	O
+hydroxylated	O
+residues	O
+with	O
+cysteines	O
+,	O
+as	O
+is	O
+found	O
+in	O
+eukaryotes	O
+(	O
+11	O
+)	O
+.	O
+
+Instead	O
+,	O
+a	O
+block	O
+of	O
+four	O
+hydroxylated	O
+amino	O
+acids	O
+was	O
+found	O
+at	O
+the	O
+amino	O
+terminus	O
+.	O
+
+The	O
+sequence	O
+of	O
+this	O
+unique	O
+MT	O
+is	O
+now	O
+nearing	O
+completion	O
+,	O
+opening	O
+the	O
+way	O
+for	O
+an	O
+X	O
+-	O
+ray	O
+crystallographic	O
+investigation	O
+.	O
+
+However	O
+,	O
+the	O
+degree	O
+of	O
+similarity	O
+between	O
+the	O
+metal	O
+cluster	O
+arrangement	O
+of	O
+these	O
+bacterial	O
+molecules	O
+with	O
+the	O
+eukaryotic	O
+structures	O
+will	O
+initially	O
+be	O
+undertaken	O
+spectroscopically	O
+.	O
+
+Reliable	O
+interpretation	O
+of	O
+the	O
+113Cd	O
+-	O
+NMR	O
+data	O
+for	O
+this	O
+molecule	O
+will	O
+be	O
+dependent	O
+upon	O
+adequate	O
+isolation	O
+of	O
+isoproteins	O
+using	O
+RP	O
+-	O
+HPLC	O
+and	O
+assessment	O
+of	O
+conformational	O
+integrity	O
+of	O
+metal	O
+reconstituted	O
+molecules	O
+,	O
+using	O
+procedures	O
+such	O
+as	O
+cyclic	O
+voltametry	O
+.	O
+
+Studies	O
+along	O
+these	O
+lines	O
+are	O
+presently	O
+underway	O
+in	O
+this	O
+laboratory	O
+
+The	O
+author	O
+gratefully	O
+acknowledges	O
+the	O
+financial	O
+support	O
+of	O
+the	O
+Australian	O
+Institute	O
+of	O
+Marine	O
+Science	O
+and	O
+the	O
+National	O
+Science	O
+and	O
+Engineering	O
+Research	O
+Council	O
+of	O
+Canada	O
+.	O
+
+Excellent	O
+technical	O
+assistance	O
+was	O
+provided	O
+by	O
+R	O
+.	O
+
+G	O
+.	O
+
+Sim	O
+and	O
+S	O
+.	O
+
+Kielland	O
+in	O
+carrying	O
+out	O
+the	O
+polarographic	O
+and	O
+sequence	O
+analyses	O
+,	O
+respectively	O
+.	O
+
+REFERENCES	O
+
+1	O
+.	O
+
+Kagi	O
+,	O
+J	O
+.	O
+
+H	O
+.	O
+
+R	O
+.	O
+,	O
+and	O
+Nordberg	O
+,	O
+M	O
+.	O
+
+(	O
+Eds	O
+.	O
+)	O
+.	O
+
+Metallothionein	O
+.	O
+
+Birk	O
+
+hauser	O
+Verlag	O
+,	O
+Basel	O
+,	O
+1979	O
+,	O
+pp	O
+.	O
+
+5	O
+-	O
+55	O
+.	O
+
+2	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+Differential	O
+pulse	O
+polarographic	O
+determination	O
+of	O
+
+murine	B
+metallothionein	O
+induction	O
+kinetics	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+256	O
+:	O
+12631268	O
+(	O
+1981	O
+)	O
+.	O
+
+3	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+Intestinal	O
+metallothionein	O
+:	O
+effect	O
+of	O
+parenteral	O
+and	O
+
+enteral	O
+zinc	O
+exposure	O
+on	O
+tissue	O
+levels	O
+of	O
+mice	B
+on	O
+controlled	O
+zinc	O
+diets	O
+.	O
+
+J	O
+.	O
+
+Nutr	O
+.	O
+
+113	O
+:	O
+268	O
+-	O
+275	O
+(	O
+1983	O
+)	O
+.	O
+
+4	O
+.	O
+
+McCarter	O
+,	O
+J	O
+.	O
+A	O
+.	O
+,	O
+and	O
+Roch	O
+,	O
+M	O
+.	O
+
+Chronic	O
+exposure	O
+of	O
+Coho	B
+salmon	I
+
+to	O
+sublethal	O
+concentrations	O
+of	O
+copper	O
+.	O
+
+III	O
+.	O
+
+Kinetics	O
+of	O
+metabolism	O
+of	O
+metallothionein	O
+.	O
+
+Comp	O
+.	O
+
+Biochem	O
+.	O
+
+Physiol	O
+.	O
+
+77C	O
+:	O
+83	O
+-	O
+87	O
+(	O
+1984	O
+)	O
+.	O
+
+5	O
+.	O
+
+Lerch	O
+,	O
+K	O
+.	O
+,	O
+Ammer	O
+,	O
+D	O
+.	O
+,	O
+and	O
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+Crab	O
+metallothionein	O
+
+primary	O
+structures	O
+of	O
+metallothioneins	O
+1	O
+and	O
+2	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+257	O
+:	O
+2420	O
+-	O
+2426	O
+(	O
+1982	O
+)	O
+.	O
+
+6	O
+.	O
+
+Otvos	O
+,	O
+J	O
+.	O
+
+D	O
+.	O
+,	O
+Olafson	O
+,	O
+R	O
+.	O
+W	O
+,	O
+and	O
+Armitage	O
+,	O
+I	O
+.	O
+
+M	O
+.	O
+
+Structure	O
+of	O
+an	O
+
+invertebrate	O
+metallothionein	O
+from	O
+Scylla	B
+serrata	I
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+257	O
+:	O
+2427	O
+-	O
+2431	O
+(	O
+1982	O
+)	O
+.	O
+
+7	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+,	O
+Abel	O
+,	O
+K	O
+.	O
+,	O
+and	O
+Sim	O
+,	O
+R	O
+.	O
+
+G	O
+.	O
+
+Prokaryotic	O
+metallothi	O
+
+onein	O
+:	O
+preliminary	O
+characteristics	O
+of	O
+a	O
+blue	O
+-	O
+green	O
+alga	O
+heavy	O
+metalbinding	O
+protein	O
+.	O
+
+Biochem	O
+.	O
+
+Biophys	O
+.	O
+
+Res	O
+.	O
+
+Commun	O
+.	O
+
+89	O
+:	O
+36	O
+-	O
+40	O
+(	O
+1979	O
+)	O
+.	O
+
+8	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+,	O
+Loya	O
+,	O
+S	O
+.	O
+,	O
+and	O
+Sim	O
+,	O
+R	O
+.	O
+
+G	O
+.	O
+
+Physiological	O
+parameters	O
+
+of	O
+prokaryotic	O
+metallothionein	O
+induction	O
+.	O
+
+Biochem	O
+.	O
+
+Biophys	O
+.	O
+
+Res	O
+.	O
+
+Commun	O
+.	O
+
+95	O
+:	O
+1495	O
+-	O
+1503	O
+(	O
+1980	O
+)	O
+.	O
+
+9	O
+.	O
+
+Brdicka	O
+,	O
+R	O
+.	O
+
+Pblarographic	O
+studies	O
+with	O
+the	O
+dropping	O
+mercury	O
+ka	O
+
+thode	O
+.	O
+-	O
+Part	O
+XXXI	O
+.	O
+-	O
+A	O
+new	O
+test	O
+for	O
+proteins	O
+in	O
+the	O
+presence	O
+of	O
+cobalt	O
+salts	O
+in	O
+ammoniacal	O
+solutions	O
+of	O
+ammonium	O
+chloride	O
+.	O
+
+Collect	O
+.	O
+
+Czech	O
+.	O
+
+Chem	O
+.	O
+
+Commun	O
+.	O
+
+5	O
+:	O
+112	O
+-	O
+128	O
+(	O
+1933	O
+)	O
+.	O
+
+10	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+,	O
+and	O
+Sim	O
+,	O
+R	O
+.	O
+
+G	O
+.	O
+
+An	O
+electrochemical	O
+approach	O
+to	O
+
+quantitation	O
+and	O
+characterization	O
+of	O
+metallothionein	O
+.	O
+
+Anal	O
+.	O
+
+Biochem	O
+.	O
+
+100	O
+:	O
+343	O
+-	O
+351	O
+(	O
+1979	O
+)	O
+.	O
+
+11	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+Differential	O
+pulse	O
+polarographic	O
+determination	O
+of	O
+
+murine	B
+metallothionein	O
+induction	O
+kinetics	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+256	O
+:	O
+12631268	O
+(	O
+1981	O
+)	O
+.	O
+
+12	O
+.	O
+
+Olafson	O
+,	O
+R	O
+.	O
+
+W	O
+Prokaryotic	O
+metallothionein	O
+:	O
+amino	O
+terminal	O
+se	O
+
+quence	O
+analysis	O
+of	O
+a	O
+unique	O
+metallothionein	O
+.	O
+
+Int	O
+.	O
+
+J	O
+.	O
+
+Peptide	O
+Protein	O
+Res	O
+.	O
+
+24	O
+:	O
+303	O
+-	O
+308	O
+(	O
+1984	O
+)	O
+.	O
+
+Peculiarities	O
+of	O
+carcinogenesis	O
+under	O
+simultaneous	O
+oral	O
+administration	O
+of	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+and	O
+o	O
+-	O
+cresol	O
+in	O
+mice	B
+.	O
+
+Abstract	O
+
+A	O
+modifying	O
+influence	O
+of	O
+ortho	O
+-	O
+cresol	O
+(	O
+o	O
+-	O
+cresol	O
+)	O
+on	O
+the	O
+carcinogenic	O
+effect	O
+of	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+(	O
+BaP	O
+)	O
+with	O
+combined	O
+oral	O
+administration	O
+to	O
+CC57Br	O
+mice	B
+had	O
+been	O
+found	O
+.	O
+
+During	O
+simultaneous	O
+administration	O
+of	O
+o	O
+-	O
+cresol	O
+(	O
+1	O
+mg	O
+)	O
+and	O
+BaP	O
+(	O
+1	O
+mg	O
+)	O
+,	O
+the	O
+incidence	O
+of	O
+tumors	O
+,	O
+the	O
+multiplicity	O
+of	O
+tumors	O
+,	O
+and	O
+the	O
+degree	O
+of	O
+malignancy	O
+all	O
+increased	O
+,	O
+but	O
+the	O
+latency	O
+was	O
+shortened	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+was	O
+administered	O
+before	O
+or	O
+after	O
+BaP	O
+(	O
+in	O
+identical	O
+doses	O
+)	O
+,	O
+the	O
+carcinogenic	O
+effect	O
+was	O
+weakened	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+(	O
+10	O
+mg	O
+)	O
+and	O
+BaP	O
+(	O
+5	O
+mg	O
+)	O
+were	O
+administered	O
+simultaneously	O
+,	O
+the	O
+incidence	O
+of	O
+malignant	O
+tumors	O
+was	O
+similar	O
+to	O
+controls	O
+receiving	O
+BaP	O
+only	O
+(	O
+13	O
+.	O
+8	O
+%	O
+)	O
+,	O
+indicating	O
+inhibition	O
+of	O
+carcinogenesis	O
+.	O
+
+Environnmental	O
+Health	O
+Perspectives	O
+Supplements	O
+Vol	O
+.	O
+
+101	O
+(	O
+Suppl	O
+.	O
+3	O
+)	O
+:	O
+341	O
+-	O
+344	O
+(	O
+1993	O
+)	O
+
+Peculiarities	O
+of	O
+Carcinogenesis	O
+under	O
+Simultaneous	O
+Oral	O
+Administration	O
+of	O
+
+Benzo	O
+(	O
+a	O
+)	O
+Pyrene	O
+and	O
+o	O
+-	O
+Cresol	O
+in	O
+Mice	B
+
+by	O
+N	O
+.	O
+
+Ya	O
+.	O
+
+Yanysheva	O
+,	O
+'	O
+N	O
+.	O
+
+V	O
+.	O
+
+Balenko	O
+,	O
+1	O
+.	O
+
+A	O
+.	O
+
+Chernichenko	O
+,	O
+1	O
+and	O
+V	O
+.	O
+
+F	O
+.	O
+
+Babiy	O
+'	O
+
+A	O
+modifying	O
+influence	O
+of	O
+ortho	O
+-	O
+cresol	O
+(	O
+o	O
+-	O
+cresol	O
+)	O
+on	O
+the	O
+carcinogenic	O
+effect	O
+of	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+(	O
+BaP	O
+)	O
+with	O
+combined	O
+oral	O
+administration	O
+to	O
+CC57Br	O
+mice	B
+had	O
+been	O
+found	O
+.	O
+
+During	O
+simultaneous	O
+administration	O
+of	O
+o	O
+-	O
+cresol	O
+(	O
+1	O
+mg	O
+)	O
+and	O
+BaP	O
+(	O
+1	O
+mg	O
+)	O
+,	O
+the	O
+incidence	O
+of	O
+tumors	O
+,	O
+the	O
+multiplicity	O
+of	O
+tumors	O
+,	O
+and	O
+the	O
+degree	O
+of	O
+malignancy	O
+all	O
+increased	O
+,	O
+but	O
+the	O
+latency	O
+was	O
+shortened	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+was	O
+administered	O
+before	O
+or	O
+after	O
+BaP	O
+(	O
+in	O
+identical	O
+doses	O
+)	O
+,	O
+the	O
+carcinogenic	O
+effect	O
+was	O
+weakened	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+(	O
+10	O
+mg	O
+)	O
+and	O
+BaP	O
+(	O
+5	O
+mg	O
+)	O
+were	O
+administered	O
+simultaneously	O
+,	O
+the	O
+incidence	O
+of	O
+malignant	O
+tumors	O
+was	O
+similar	O
+to	O
+controls	O
+receiving	O
+BaP	O
+only	O
+(	O
+13	O
+.	O
+8	O
+%	O
+)	O
+,	O
+indicating	O
+inhibition	O
+of	O
+carcinogenesis	O
+.	O
+
+Introduction	O
+
+Numerous	O
+experiments	O
+have	O
+shown	O
+a	O
+modifying	O
+influence	O
+of	O
+different	O
+chemicals	O
+on	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+(	O
+BaP	O
+)	O
+induced	O
+carcinogenic	O
+effects	O
+.	O
+
+Both	O
+enhancing	O
+or	O
+weakening	O
+effects	O
+have	O
+been	O
+seen	O
+(	O
+1	O
+-	O
+12	O
+)	O
+.	O
+
+In	O
+some	O
+experiments	O
+ubiquitious	O
+environmental	O
+carcinogenic	O
+and	O
+toxic	O
+chemical	O
+pollutants	O
+were	O
+used	O
+(	O
+13	O
+-	O
+17	O
+)	O
+.	O
+
+The	O
+stimulating	O
+effect	O
+of	O
+phenol	O
+,	O
+nitrogen	O
+oxides	O
+,	O
+and	O
+sulfur	O
+dioxide	O
+upon	O
+BaP	O
+'	O
+s	O
+blastogenic	O
+action	O
+on	O
+the	O
+respiratory	O
+tract	O
+and	O
+phenol	O
+on	O
+the	O
+digestive	O
+tract	O
+(	O
+forestomach	O
+)	O
+have	O
+been	O
+reported	O
+(	O
+12	O
+-	O
+18	O
+)	O
+.	O
+
+We	O
+have	O
+established	O
+the	O
+relationship	O
+between	O
+the	O
+doses	O
+of	O
+carcinogenic	O
+and	O
+toxic	O
+agents	O
+and	O
+their	O
+modifying	O
+effects	O
+(	O
+17	O
+,	O
+18	O
+)	O
+.	O
+
+The	O
+maximal	O
+enhancing	O
+effect	O
+was	O
+observed	O
+after	O
+BaP	O
+(	O
+2	O
+.	O
+5	O
+mg	O
+)	O
+and	O
+NO2	O
+(	O
+0	O
+.	O
+87	O
+mg	O
+/	O
+m3	O
+)	O
+were	O
+exposed	O
+to	O
+rat	B
+respiratory	O
+tract	O
+.	O
+
+The	O
+effect	O
+weakened	O
+with	O
+decreasing	O
+dose	O
+.	O
+
+At	O
+concentrations	O
+at	O
+the	O
+MPC	O
+level	O
+(	O
+MPC	O
+BaP	O
+,	O
+1	O
+ng	O
+/	O
+m3	O
+,	O
+MPC	O
+NO2	O
+,	O
+0	O
+.	O
+04	O
+mg	O
+/	O
+m3	O
+)	O
+no	O
+effect	O
+was	O
+seen	O
+.	O
+
+Phenol	O
+at	O
+1	O
+mg	O
+orally	O
+to	O
+CC57Br	O
+mice	B
+enhanced	O
+the	O
+BaP	O
+(	O
+1	O
+mg	O
+)	O
+effect	O
+,	O
+but	O
+no	O
+effect	O
+was	O
+seen	O
+at	O
+0	O
+.	O
+02	O
+mg	O
+.	O
+
+Phenolic	O
+compounds	O
+showed	O
+either	O
+enhancing	O
+or	O
+inhibiting	O
+effects	O
+on	O
+carcinogenesis	O
+depending	O
+on	O
+their	O
+chemical	O
+structure	O
+(	O
+16	O
+,	O
+18	O
+-	O
+25	O
+)	O
+.	O
+
+This	O
+report	O
+presents	O
+the	O
+results	O
+of	O
+combined	O
+oral	O
+administration	O
+of	O
+BaP	O
+and	O
+artho	O
+-	O
+cresol	O
+(	O
+o	O
+-	O
+cresol	O
+)	O
+in	O
+mice	B
+,	O
+
+'	O
+Ukrainian	O
+State	O
+Medical	O
+Center	O
+for	O
+Environmental	O
+Health	O
+,	O
+Kiev	O
+,	O
+Ukraine	O
+.	O
+
+Address	O
+reprint	O
+requests	O
+to	O
+N	O
+.	O
+
+Y	O
+.	O
+
+Yanysheva	O
+,	O
+Ukrainian	O
+State	O
+Medical	O
+Center	O
+for	O
+Environmental	O
+Health	O
+,	O
+Popudrenko	O
+St	O
+.	O
+
+50	O
+,	O
+253660	O
+Kiev	O
+-	O
+94	O
+,	O
+Ukraine	O
+.	O
+
+chemicals	O
+commonly	O
+found	O
+in	O
+ambient	O
+water	O
+because	O
+of	O
+their	O
+industrial	O
+use	O
+(	O
+coke	O
+chemistry	O
+,	O
+oil	O
+processing	O
+,	O
+shale	O
+processing	O
+,	O
+and	O
+other	O
+industries	O
+)	O
+(	O
+27	O
+-	O
+30	O
+)	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+The	O
+experiment	O
+was	O
+conducted	O
+on	O
+CC57Br	O
+female	O
+mice	B
+weighing	O
+12	O
+-	O
+14	O
+g	O
+.	O
+
+Animals	O
+were	O
+divided	O
+in	O
+15	O
+groups	O
+.	O
+
+This	O
+experiment	O
+included	O
+three	O
+types	O
+of	O
+sequential	O
+combinations	O
+for	O
+the	O
+introduction	O
+of	O
+compounds	O
+:	O
+a	O
+)	O
+simultaneous	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+administration	O
+;	O
+b	O
+)	O
+BaP	O
+after	O
+o	O
+-	O
+cresol	O
+(	O
+stage	O
+1	O
+)	O
+;	O
+and	O
+c	O
+)	O
+BaP	O
+before	O
+o	O
+-	O
+cresol	O
+(	O
+stage	O
+2	O
+)	O
+.	O
+
+Appropriate	O
+controls	O
+were	O
+included	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+The	O
+chemicals	O
+were	O
+administered	O
+twice	O
+per	O
+week	O
+(	O
+for	O
+a	O
+total	O
+of	O
+10	O
+,	O
+20	O
+,	O
+and	O
+40	O
+doses	O
+)	O
+using	O
+a	O
+syringe	O
+and	O
+a	O
+needle	O
+with	O
+a	O
+soldered	O
+olive	O
+on	O
+its	O
+tip	O
+.	O
+
+BaP	O
+(	O
+1	O
+or	O
+5	O
+mg	O
+)	O
+or	O
+o	O
+-	O
+cresol	O
+(	O
+0	O
+.	O
+02	O
+,	O
+1	O
+,	O
+or	O
+10	O
+mg	O
+)	O
+was	O
+placed	O
+in	O
+triethylene	O
+glycol	O
+(	O
+TEG	O
+)	O
+and	O
+administered	O
+as	O
+0	O
+.	O
+1	O
+-	O
+mL	O
+water	O
+solutions	O
+.	O
+
+The	O
+evaluation	O
+of	O
+o	O
+-	O
+cresol	O
+'	O
+s	O
+modifying	O
+effect	O
+on	O
+the	O
+incidence	O
+of	O
+tumors	O
+,	O
+especially	O
+malignant	O
+tumors	O
+,	O
+the	O
+tumor	O
+latency	O
+period	O
+(	O
+tl	O
+)	O
+,	O
+and	O
+the	O
+average	O
+time	O
+(	O
+ta	O
+)	O
+of	O
+the	O
+appearance	O
+of	O
+tumors	O
+,	O
+as	O
+well	O
+as	O
+the	O
+multiplicity	O
+index	O
+,	O
+M	O
+(	O
+the	O
+average	O
+number	O
+of	O
+tumors	O
+per	O
+animal	O
+for	O
+tumor	O
+-	O
+bearing	O
+animals	O
+)	O
+was	O
+recorded	O
+.	O
+
+Because	O
+the	O
+M	O
+could	O
+be	O
+identified	O
+at	O
+the	O
+initial	O
+stage	O
+of	O
+carcinogenesis	O
+by	O
+the	O
+third	O
+month	O
+after	O
+the	O
+beginning	O
+of	O
+the	O
+trial	O
+when	O
+neoplasms	O
+began	O
+to	O
+emerge	O
+,	O
+moribund	O
+animals	O
+were	O
+killed	O
+by	O
+ether	O
+inhalation	O
+if	O
+they	O
+did	O
+not	O
+die	O
+spontaneously	O
+.	O
+
+The	O
+experiments	O
+with	O
+large	O
+chemical	O
+doses	O
+(	O
+BaP	O
+,	O
+5	O
+mg	O
+;	O
+o	O
+-	O
+cresol	O
+,	O
+10	O
+mg	O
+)	O
+lasted	O
+for	O
+30	O
+weeks	O
+.	O
+
+Some	O
+animals	O
+were	O
+killed	O
+after	O
+the	O
+1st	O
+,	O
+3rd	O
+,	O
+5th	O
+,	O
+and	O
+10th	O
+procedures	O
+for	O
+the	O
+
+YANYSHEVA	O
+ET	O
+AL	O
+.	O
+
+evaluation	O
+of	O
+initial	O
+stages	O
+of	O
+carcinogenesis	O
+;	O
+others	O
+were	O
+killed	O
+at	O
+26	O
+and	O
+30	O
+weeks	O
+.	O
+
+The	O
+stomachs	O
+were	O
+distended	O
+with	O
+formalin	O
+solution	O
+and	O
+the	O
+mucosa	O
+examined	O
+macroscopically	O
+.	O
+
+All	O
+tumors	O
+>	O
+1	O
+mm	O
+in	O
+diameter	O
+were	O
+recorded	O
+.	O
+
+Organs	O
+and	O
+tissues	O
+were	O
+fised	O
+in	O
+10	O
+%	O
+neutral	O
+formalin	O
+solution	O
+,	O
+embedded	O
+in	O
+paraffin	O
+and	O
+routine	O
+histological	O
+slides	O
+prepared	O
+.	O
+
+Microscopic	O
+data	O
+were	O
+processed	O
+according	O
+to	O
+Mostkovoy	O
+(	O
+30	O
+)	O
+.	O
+
+Results	O
+
+The	O
+data	O
+from	O
+this	O
+study	O
+demonstrate	O
+the	O
+modifying	O
+influence	O
+of	O
+o	O
+-	O
+cresol	O
+on	O
+BaP	O
+-	O
+induced	O
+carcinogenesis	O
+with	O
+combined	O
+oral	O
+exposure	O
+.	O
+
+The	O
+combined	O
+exposure	O
+and	O
+BaP	O
+alone	O
+caused	O
+benign	O
+and	O
+malignant	O
+epithelial	O
+tumors	O
+of	O
+the	O
+forestomach	O
+.	O
+
+The	O
+benign	O
+neoplasms	O
+were	O
+papillomas	O
+,	O
+and	O
+the	O
+malignant	O
+neoplasms	O
+were	O
+invasive	O
+carcinomas	O
+.	O
+
+The	O
+combined	O
+administration	O
+of	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+showed	O
+different	O
+results	O
+depending	O
+on	O
+doses	O
+and	O
+sequential	O
+combinations	O
+of	O
+both	O
+chemicals	O
+.	O
+
+As	O
+shown	O
+in	O
+Table	O
+2	O
+,	O
+the	O
+simultaneous	O
+administration	O
+of	O
+BaP	O
+(	O
+1	O
+mg	O
+)	O
+and	O
+o	O
+-	O
+cresol	O
+(	O
+1	O
+mg	O
+)	O
+affected	O
+all	O
+parameters	O
+of	O
+carcinogenesis	O
+that	O
+were	O
+measured	O
+.	O
+
+This	O
+included	O
+a	O
+significant	O
+increase	O
+in	O
+the	O
+incidence	O
+of	O
+tumors	O
+,	O
+shortening	O
+of	O
+the	O
+time	O
+to	O
+the	O
+appearance	O
+of	O
+the	O
+first	O
+tumor	O
+,	O
+and	O
+the	O
+mean	O
+time	O
+of	O
+tumor	O
+
+development	O
+as	O
+compared	O
+to	O
+animals	O
+that	O
+received	O
+1	O
+mg	O
+of	O
+BaP	O
+alone	O
+and	O
+had	O
+tumors	O
+.	O
+
+One	O
+hundred	O
+percent	O
+of	O
+the	O
+mice	B
+that	O
+received	O
+5	O
+mg	O
+of	O
+BaP	O
+alone	O
+had	O
+tumors	O
+.	O
+
+Shortening	O
+of	O
+the	O
+time	O
+to	O
+appearance	O
+of	O
+malignant	O
+tumors	O
+was	O
+also	O
+observed	O
+:	O
+the	O
+mice	B
+with	O
+forestomach	O
+cancer	O
+died	O
+between	O
+23	O
+and	O
+26	O
+.	O
+2	O
+weeks	O
+after	O
+the	O
+beginning	O
+of	O
+experiment	O
+,	O
+but	O
+the	O
+controls	O
+survived	O
+to	O
+58	O
+.	O
+5	O
+weeks	O
+.	O
+
+Muliple	O
+small	O
+metastases	O
+in	O
+the	O
+lungs	O
+and	O
+mediastinum	O
+were	O
+found	O
+in	O
+42	O
+.	O
+8	O
+%	O
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+,	O
+which	O
+signifies	O
+a	O
+high	O
+degree	O
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+malignancy	O
+.	O
+
+o	O
+-	O
+Cresol	O
+at	O
+0	O
+.	O
+02	O
+mg	O
+did	O
+not	O
+modify	O
+carcinogenesis	O
+in	O
+comparison	O
+to	O
+the	O
+control	O
+.	O
+
+o	O
+-	O
+Cresol	O
+administration	O
+before	O
+or	O
+after	O
+BaP	O
+did	O
+not	O
+modify	O
+tumor	O
+incidence	O
+or	O
+the	O
+multiplicity	O
+index	O
+as	O
+compared	O
+to	O
+control	O
+,	O
+but	O
+the	O
+latency	O
+period	O
+was	O
+longer	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+was	O
+administered	O
+after	O
+BaP	O
+(	O
+stage	O
+2	O
+)	O
+,	O
+there	O
+was	O
+an	O
+absence	O
+of	O
+malignant	O
+tumors	O
+.	O
+
+Besides	O
+the	O
+quantitative	O
+aspects	O
+,	O
+other	O
+peculiarities	O
+of	O
+carcinogenesis	O
+in	O
+mice	B
+simultaneously	O
+administered	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+should	O
+be	O
+noted	O
+.	O
+
+The	O
+combined	O
+chemical	O
+administration	O
+resulted	O
+in	O
+diffuse	O
+verrucosa	O
+vegetations	O
+over	O
+the	O
+forestomach	O
+surface	O
+,	O
+especially	O
+near	O
+the	O
+greater	O
+curvature	O
+.	O
+
+Highly	O
+aggressive	O
+malignant	O
+neoplasms	O
+developed	O
+earlier	O
+with	O
+more	O
+metastases	O
+as	O
+compared	O
+to	O
+control	O
+.	O
+
+Many	O
+mice	B
+were	O
+emaciated	O
+,	O
+and	O
+the	O
+tumors	O
+could	O
+be	O
+
+Table	O
+1	O
+.	O
+
+Scheme	O
+of	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+combined	O
+action	O
+under	O
+different	O
+regimes	O
+of	O
+oral	O
+administration	O
+.	O
+
+Theatmenta	O
+
+No	O
+.	O
+of	O
+mice	B
+Stage	O
+1	O
+Stage	O
+2	O
+
+Groups	O
+of	O
+in	O
+each	O
+No	O
+.	O
+of	O
+No	O
+.	O
+of	O
+
+animals	O
+group	O
+Substances	O
+Dose	O
+,	O
+mg	O
+applications	O
+Substances	O
+Dose	O
+,	O
+mg	O
+applications	O
+
+1	O
+55	O
+BaP	O
+,	O
+o	O
+-	O
+cresol	O
+5	O
++	O
+10	O
+10	O
+-	O
+-	O
+2	O
+45	O
+BaP	O
+5	O
+10	O
+-	O
+-	O
+3	O
+40	O
+TEG	O
+la	O
+10	O
+-	O
+-	O
+4	O
+45	O
+TEG	O
+,	O
+o	O
+-	O
+cresol	O
+1b	O
++	O
+10	O
+10	O
+-	O
+-	O
+5	O
+30	O
+BaP	O
+,	O
+o	O
+-	O
+cresol	O
+1	O
++	O
+1	O
+20	O
+-	O
+-	O
+6	O
+30	O
+BaP	O
+,	O
+o	O
+-	O
+cresol	O
+1	O
++	O
+0	O
+.	O
+02	O
+20	O
+-	O
+-	O
+7	O
+30	O
+o	O
+-	O
+Cresol	O
+1	O
+20	O
+BaP	O
+1	O
+20	O
+8	O
+30	O
+BaP	O
+1	O
+20	O
+o	O
+-	O
+Cresol	O
+1	O
+20	O
+9	O
+30	O
+BaP	O
+1	O
+20	O
+-	O
+10	O
+30	O
+-	O
+-	O
+-	O
+BaP	O
+1	O
+20	O
+11	O
+30	O
+o	O
+-	O
+Cresol	O
+1	O
+20	O
+-	O
+12	O
+30	O
+-	O
+-	O
+-	O
+o	O
+-	O
+Cresol	O
+1	O
+20	O
+13	O
+30	O
+o	O
+-	O
+Cresol	O
++	O
+TEG	O
+1	O
++	O
+2	O
+'	O
+20	O
+-	O
+14	O
+30	O
+o	O
+-	O
+Cresol	O
++	O
+TEG	O
+0	O
+.	O
+02	O
++	O
+2b	O
+20	O
+
+15	O
+30	O
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+2b	O
+20	O
+-	O
+-	O
+Abbreviations	O
+:	O
+BaP	O
+,	O
+benzo	O
+[	O
+a	O
+]	O
+pyrene	O
+;	O
+TEG	O
+,	O
+triethylene	O
+glycol	O
+.	O
+
+Table	O
+2	O
+.	O
+
+Occurrence	O
+of	O
+forestomach	O
+tumors	O
+in	O
+CC57Br	O
+mice	B
+after	O
+combined	O
+oral	O
+administration	O
+of	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+.	O
+
+Number	O
+of	O
+animals	O
+with	O
+forestomach	O
+tumors	O
+
+Order	O
+of	O
+administration	O
+of	O
+substances	O
+Total	O
+Benign	O
+Malignant	O
+
+(	O
+dose	O
+,	O
+mg	O
+)	O
+Absolute	O
+%	O
+%	O
+M	O
+t	O
+,	O
+ta	O
+%	O
+t	O
+,	O
+ta	O
+BaP	O
+(	O
+5	O
+)	O
+,	O
+o	O
+-	O
+cresol	O
+(	O
+10	O
+)	O
+29	O
+100	O
+.	O
+0	O
+86	O
+.	O
+2	O
+ND	O
+ND	O
+ND	O
+13	O
+.	O
+8	O
+ND	O
+ND	O
+BaP	O
+(	O
+1	O
+)	O
+,	O
+o	O
+-	O
+cresol	O
+(	O
+1	O
+)	O
+19	O
+95	O
+.	O
+0	O
+60	O
+.	O
+0	O
+9	O
+.	O
+6	O
+10	O
+.	O
+7	O
+16	O
+.	O
+3	O
+35	O
+.	O
+0	O
+23	O
+.	O
+0	O
+25	O
+.	O
+2	O
+BaP	O
+(	O
+1	O
+)	O
+,	O
+o	O
+-	O
+cresol	O
+(	O
+0	O
+.	O
+02	O
+)	O
+7	O
+35	O
+.	O
+0	O
+30	O
+.	O
+0	O
+1	O
+.	O
+6	O
+13	O
+.	O
+5	O
+19	O
+.	O
+8	O
+5	O
+.	O
+0	O
+56	O
+.	O
+8	O
+56	O
+.	O
+8	O
+BaP	O
+(	O
+1	O
+)	O
+,	O
+stage	O
+1	O
+,	O
+o	O
+-	O
+cresol	O
+(	O
+1	O
+)	O
+,	O
+stage	O
+2	O
+7	O
+31	O
+.	O
+8	O
+31	O
+.	O
+8	O
+1	O
+.	O
+4	O
+16	O
+.	O
+2	O
+31	O
+.	O
+1	O
+0	O
+0	O
+0	O
+
+BaP	O
+(	O
+1	O
+)	O
+,	O
+stage	O
+2	O
+6	O
+35	O
+.	O
+3	O
+29	O
+.	O
+4	O
+2	O
+.	O
+8	O
+15	O
+.	O
+8	O
+41	O
+.	O
+2	O
+5	O
+.	O
+9	O
+24	O
+.	O
+8	O
+24	O
+.	O
+8	O
+BaP	O
+(	O
+5	O
+)	O
+,	O
+stage	O
+1	O
+18	O
+100	O
+.	O
+0	O
+50	O
+.	O
+0	O
+ND	O
+ND	O
+ND	O
+50	O
+.	O
+0	O
+ND	O
+ND	O
+BaP	O
+(	O
+1	O
+)	O
+,	O
+stage	O
+1	O
+8	O
+33	O
+.	O
+3	O
+28	O
+.	O
+7	O
+1	O
+.	O
+4	O
+14	O
+.	O
+0	O
+21	O
+.	O
+3	O
+4	O
+.	O
+6	O
+58	O
+.	O
+5	O
+58	O
+.	O
+5	O
+BaP	O
+(	O
+1	O
+)	O
+,	O
+stage	O
+2	O
+7	O
+36	O
+.	O
+8	O
+31	O
+.	O
+6	O
+2	O
+.	O
+8	O
+10	O
+.	O
+0	O
+13	O
+.	O
+3	O
+5	O
+.	O
+2	O
+55	O
+.	O
+7	O
+55	O
+.	O
+7	O
+
+Abbreviations	O
+:	O
+BaP	O
+,	O
+benzo	O
+[	O
+a	O
+]	O
+pyrene	O
+;	O
+0	O
+,	O
+not	O
+observed	O
+;	O
+ND	O
+,	O
+not	O
+determined	O
+;	O
+t1	O
+,	O
+time	O
+of	O
+the	O
+first	O
+tumor	O
+appearance	O
+in	O
+weeks	O
+;	O
+ta	O
+,	O
+mean	O
+time	O
+of	O
+tumor	O
+development	O
+in	O
+weeks	O
+;	O
+M	O
+,	O
+multiplicity	O
+.	O
+
+342	O
+
+CARCINOGENESIS	O
+OF	O
+BaP	O
+AND	O
+o	O
+-	O
+CRESOL	O
+343	O
+
+palpated	O
+through	O
+the	O
+abdominal	O
+wall	O
+.	O
+
+At	O
+autopsy	O
+,	O
+enlargement	O
+of	O
+the	O
+stomach	O
+with	O
+tuberculous	O
+white	O
+superficial	O
+vegetations	O
+were	O
+observed	O
+.	O
+
+The	O
+forestomach	O
+and	O
+glandular	O
+part	O
+of	O
+the	O
+stomach	O
+was	O
+often	O
+obliterated	O
+by	O
+tumor	O
+masses	O
+.	O
+
+The	O
+stomach	O
+was	O
+often	O
+adhered	O
+to	O
+the	O
+pancreas	O
+,	O
+liver	O
+,	O
+and	O
+mesentery	O
+.	O
+
+Hemmorrhage	O
+and	O
+inflammation	O
+were	O
+found	O
+in	O
+tumors	O
+foci	O
+.	O
+
+When	O
+o	O
+-	O
+cresol	O
+was	O
+introduced	O
+before	O
+BaP	O
+,	O
+the	O
+tumors	O
+were	O
+more	O
+frequently	O
+found	O
+closer	O
+to	O
+the	O
+small	O
+curvature	O
+of	O
+the	O
+stomach	O
+between	O
+the	O
+forestomach	O
+and	O
+esophageal	O
+entrance	O
+.	O
+
+Over	O
+the	O
+large	O
+curvature	O
+less	O
+prominent	O
+mucosal	O
+folds	O
+were	O
+observed	O
+.	O
+
+Microscopically	O
+,	O
+a	O
+decrease	O
+in	O
+mucosa	O
+papillae	O
+,	O
+epithelial	O
+atrophy	O
+(	O
+one	O
+to	O
+two	O
+cullular	O
+layers	O
+)	O
+,	O
+decreased	O
+keratonization	O
+,	O
+and	O
+nuclear	O
+pycnosis	O
+were	O
+observed	O
+.	O
+
+With	O
+the	O
+simultaneous	O
+administration	O
+of	O
+large	O
+doses	O
+of	O
+o	O
+-	O
+cresol	O
+and	O
+BaP	O
+,	O
+the	O
+final	O
+carcinogenic	O
+effect	O
+(	O
+30	O
+weeks	O
+after	O
+the	O
+first	O
+dose	O
+)	O
+was	O
+similar	O
+to	O
+BaP	O
+alone	O
+but	O
+differences	O
+were	O
+observed	O
+at	O
+the	O
+earlier	O
+stages	O
+(	O
+after	O
+the	O
+1st	O
+,	O
+3rd	O
+,	O
+5th	O
+,	O
+and	O
+10th	O
+exposures	O
+)	O
+.	O
+
+In	O
+the	O
+BaP	O
+control	O
+,	O
+multiple	O
+forestomach	O
+epithelial	O
+proliferative	O
+and	O
+hyperplastic	O
+changes	O
+were	O
+found	O
+after	O
+the	O
+third	O
+dose	O
+.	O
+
+Multiple	O
+papillomas	O
+occurred	O
+(	O
+9	O
+-	O
+15	O
+in	O
+each	O
+mouse	B
+)	O
+.	O
+
+The	O
+stomach	O
+'	O
+s	O
+mucosal	O
+folds	O
+appeared	O
+thickened	O
+diffusely	O
+,	O
+then	O
+papillomas	O
+appeared	O
+and	O
+finally	O
+merged	O
+together	O
+.	O
+
+Approximately	O
+half	O
+of	O
+the	O
+tumors	O
+were	O
+malignant	O
+.	O
+
+The	O
+neoplasms	O
+filled	O
+almost	O
+the	O
+whole	O
+forestomach	O
+cavity	O
+and	O
+infiltrated	O
+the	O
+wall	O
+with	O
+tuberculous	O
+vegetations	O
+,	O
+which	O
+were	O
+visible	O
+on	O
+the	O
+serosal	O
+surface	O
+.	O
+
+Thmor	O
+infiltration	O
+in	O
+the	O
+liver	O
+,	O
+pancreas	O
+,	O
+and	O
+wide	O
+dissemination	O
+of	O
+peritoneum	O
+were	O
+also	O
+observed	O
+.	O
+
+In	O
+mice	B
+simultaneously	O
+administered	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+,	O
+the	O
+proliferative	O
+alterations	O
+of	O
+forestomach	O
+epithelium	O
+were	O
+seen	O
+after	O
+the	O
+third	O
+dose	O
+.	O
+
+However	O
+,	O
+they	O
+occurred	O
+as	O
+the	O
+single	O
+foci	O
+at	O
+damaged	O
+mucosa	O
+and	O
+even	O
+in	O
+the	O
+later	O
+stages	O
+were	O
+not	O
+diffuse	O
+.	O
+
+Adjacent	O
+to	O
+the	O
+hyperplastic	O
+foci	O
+,	O
+the	O
+mucosa	O
+was	O
+atrophied	O
+with	O
+decreased	O
+keratonization	O
+.	O
+
+The	O
+epithelial	O
+cells	O
+also	O
+showed	O
+cytoplasm	O
+coagulation	O
+and	O
+nuclear	O
+pycnosis	O
+.	O
+
+Edema	O
+,	O
+inflammation	O
+of	O
+the	O
+mucosa	O
+,	O
+submucosa	O
+microabscesses	O
+,	O
+and	O
+erosion	O
+were	O
+seen	O
+.	O
+
+There	O
+were	O
+fewer	O
+papillomas	O
+per	O
+mouse	B
+(	O
+four	O
+to	O
+eight	O
+in	O
+each	O
+mouse	B
+)	O
+than	O
+in	O
+the	O
+control	O
+group	O
+.	O
+
+Even	O
+in	O
+the	O
+late	O
+stages	O
+the	O
+papillomas	O
+were	O
+isolated	O
+and	O
+elevated	O
+on	O
+the	O
+atrophied	O
+mucosal	O
+folds	O
+.	O
+
+In	O
+the	O
+final	O
+experiment	O
+the	O
+papillomas	O
+prevailed	O
+as	O
+compared	O
+to	O
+the	O
+previous	O
+experiments	O
+.	O
+
+Only	O
+4	O
+out	O
+of	O
+29	O
+mice	B
+(	O
+13	O
+.	O
+8	O
+%	O
+)	O
+developed	O
+malignant	O
+tumors	O
+.	O
+
+Neoplasms	O
+were	O
+smaller	O
+and	O
+appeared	O
+as	O
+single	O
+verrucosa	O
+vegetations	O
+5	O
+-	O
+10	O
+mm	O
+in	O
+diameter	O
+.	O
+
+Thus	O
+,	O
+the	O
+toxic	O
+dose	O
+of	O
+o	O
+-	O
+cresol	O
+inhibits	O
+the	O
+carcinogenic	O
+process	O
+of	O
+induced	O
+forestomach	O
+tumors	O
+by	O
+decreasing	O
+multiplicity	O
+,	O
+frequency	O
+,	O
+and	O
+percentage	O
+of	O
+malignant	O
+tumors	O
+.	O
+
+Discussion	O
+
+Our	O
+results	O
+and	O
+the	O
+literature	O
+suggest	O
+a	O
+hypothesis	O
+on	O
+modifying	O
+carcinogenesis	O
+mechanisms	O
+.	O
+
+The	O
+primary	O
+effect	O
+of	O
+the	O
+toxic	O
+agents	O
+,	O
+including	O
+carcinogenic	O
+agents	O
+,	O
+may	O
+relate	O
+to	O
+cellular	O
+membrane	O
+damage	O
+with	O
+the	O
+subsequent	O
+increased	O
+permeability	O
+(	O
+31	O
+-	O
+35	O
+)	O
+,	O
+which	O
+may	O
+be	O
+the	O
+mechanism	O
+of	O
+the	O
+o	O
+-	O
+cresol	O
+.	O
+
+With	O
+simultaneous	O
+introduction	O
+of	O
+o	O
+-	O
+cresol	O
+at	O
+low	O
+toxic	O
+doses	O
+and	O
+BaP	O
+there	O
+may	O
+be	O
+increased	O
+carcinogen	O
+penetration	O
+to	O
+the	O
+target	O
+cells	O
+.	O
+
+In	O
+addition	O
+,	O
+membrane	O
+damage	O
+may	O
+alter	O
+other	O
+cellular	O
+systems	O
+responsible	O
+for	O
+energy	O
+and	O
+xenobiotic	O
+detoxication	O
+.	O
+
+Damage	O
+of	O
+these	O
+processes	O
+may	O
+activate	O
+free	O
+-	O
+radical	O
+reactions	O
+,	O
+glycolysis	O
+,	O
+or	O
+alter	O
+carcinogenic	O
+metabolism	O
+,	O
+which	O
+promotes	O
+the	O
+oncogenic	O
+effect	O
+.	O
+
+The	O
+o	O
+-	O
+cresol	O
+effect	O
+on	O
+these	O
+systems	O
+was	O
+confirmed	O
+by	O
+our	O
+previous	O
+investigations	O
+on	O
+cytochrome	O
+P450	O
+,	O
+ferrosulfuric	O
+nonhemic	O
+proteins	O
+,	O
+and	O
+semiquinon	O
+radical	O
+content	O
+affected	O
+by	O
+the	O
+combined	O
+action	O
+of	O
+BaP	O
+and	O
+o	O
+-	O
+cresol	O
+(	O
+36	O
+)	O
+.	O
+
+Another	O
+effect	O
+was	O
+obtained	O
+with	O
+BaP	O
+exposure	O
+after	O
+o	O
+-	O
+cresol	O
+.	O
+
+The	O
+atrophic	O
+alterations	O
+in	O
+the	O
+stomach	O
+induced	O
+by	O
+2	O
+.	O
+5	O
+months	O
+of	O
+o	O
+-	O
+cresol	O
+administration	O
+might	O
+decrease	O
+the	O
+natural	O
+conditions	O
+of	O
+retention	O
+(	O
+muscosal	O
+folds	O
+,	O
+frontier	O
+torn	O
+)	O
+,	O
+and	O
+thus	O
+shorten	O
+the	O
+contact	O
+of	O
+BaP	O
+with	O
+the	O
+forestomach	O
+.	O
+
+In	O
+our	O
+opinion	O
+,	O
+this	O
+explains	O
+the	O
+decreased	O
+carcinogenic	O
+effect	O
+seen	O
+after	O
+o	O
+-	O
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+exposure	O
+.	O
+
+Considering	O
+the	O
+toxic	O
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+o	O
+-	O
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+(	O
+1	O
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+)	O
+after	O
+BaP	O
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+effect	O
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+(	O
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+)	O
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+BaP	O
+administration	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+the	O
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+of	O
+carcinogenesis	O
+in	O
+both	O
+trials	O
+was	O
+related	O
+to	O
+the	O
+toxic	O
+effects	O
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+-	O
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+.	O
+
+Cytotoxicity	O
+may	O
+not	O
+only	O
+hamper	O
+tumor	O
+growth	O
+,	O
+but	O
+also	O
+promote	O
+the	O
+regression	O
+of	O
+inducible	O
+and	O
+spontaneous	O
+neoplasms	O
+(	O
+37	O
+-	O
+39	O
+)	O
+.	O
+
+There	O
+is	O
+also	O
+a	O
+possibility	O
+that	O
+BaP	O
+damages	O
+metabolic	O
+systems	O
+and	O
+decreases	O
+resistance	O
+to	O
+carcinogenesis	O
+.	O
+
+Conclusions	O
+
+The	O
+data	O
+obtained	O
+demonstrate	O
+that	O
+simultaneous	O
+administration	O
+of	O
+BaP	O
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+carcinogenesis	O
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+on	O
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+the	O
+sequence	O
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+administration	O
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+
+Administered	O
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+(	O
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+)	O
+,	O
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+(	O
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+)	O
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+an	O
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+cocarcinogenic	O
+effect	O
+reflected	O
+in	O
+the	O
+incidence	O
+,	O
+frequency	O
+,	O
+multiplicity	O
+,	O
+and	O
+degree	O
+of	O
+malignancy	O
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+forestomach	O
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+.	O
+
+o	O
+-	O
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+(	O
+1	O
+mg	O
+)	O
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+its	O
+administration	O
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+(	O
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+)	O
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+the	O
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+(	O
+5	O
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+)	O
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+carcinogenesis	O
+.	O
+
+Simultaneous	O
+introduction	O
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+noneffective	O
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+-	O
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+(	O
+0	O
+.	O
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+)	O
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+(	O
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+.	O
+
+Controlling	O
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+in	O
+the	O
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+the	O
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+is	O
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+of	O
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+.	O
+
+REFERENCES	O
+
+1	O
+.	O
+
+Bingham	O
+,	O
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+.	O
+,	O
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+,	O
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+.	O
+
+L	O
+.	O
+
+Environmental	O
+carcinogenesis	O
+.	O
+
+The	O
+
+modifying	O
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+the	O
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+.	O
+
+Arch	O
+.	O
+
+Environ	O
+.	O
+
+Health	O
+19	O
+:	O
+779	O
+-	O
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+(	O
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+)	O
+.	O
+
+2	O
+.	O
+
+Goldschmidt	O
+,	O
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+.	O
+
+M	O
+.	O
+,	O
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+,	O
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+,	O
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+,	O
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+
+L	O
+.	O
+
+The	O
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+
+cinogenic	O
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+-	O
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+.	O
+
+Proc	O
+.	O
+
+Am	O
+.	O
+
+Assoc	O
+.	O
+
+Cancer	O
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+
+17	O
+:	O
+84	O
+(	O
+1973	O
+)	O
+.	O
+
+3	O
+.	O
+
+Kaufman	O
+,	O
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+
+C	O
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+,	O
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+,	O
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+
+M	O
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+
+Synergistic	O
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+benzo	O
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+)	O
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+-	O
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+-	O
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+-	O
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+carcinogenesis	O
+in	O
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+.	O
+
+In	O
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+Sym	O
+
+344	O
+YANYSHEVA	O
+ET	O
+AL	O
+.	O
+
+posium	O
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+Respiratory	O
+Carcinogenesis	O
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+.	O
+
+Batelle	O
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+Research	O
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+,	O
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+,	O
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+,	O
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+,	O
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+.	O
+
+17	O
+.	O
+
+4	O
+.	O
+
+Montesano	O
+,	O
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+.	O
+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+.	O
+
+Synergistic	O
+
+effects	O
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+(	O
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+)	O
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+diethylnitrosamine	O
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+.	O
+
+J	O
+.	O
+
+Natl	O
+.	O
+
+Cancer	O
+.	O
+
+Inst	O
+.	O
+
+5	O
+:	O
+1395	O
+-	O
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+)	O
+.	O
+
+5	O
+.	O
+
+Pfeiffer	O
+,	O
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+
+H	O
+.	O
+
+Investigations	O
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+
+pollution	O
+in	O
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+.	O
+
+VII	O
+.	O
+
+Studies	O
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+of	O
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+.	O
+
+Zbl	O
+.	O
+
+Bakteriol	O
+.	O
+
+Parasitenk	O
+.	O
+
+Infektion	O
+.	O
+
+Hyg	O
+.	O
+
+Abt	O
+.	O
+
+B	O
+158	O
+(	O
+1	O
+)	O
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+69	O
+-	O
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+(	O
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+)	O
+.	O
+
+6	O
+.	O
+
+Slaga	O
+,	O
+T	O
+.	O
+
+J	O
+.	O
+,	O
+Jecker	O
+,	O
+L	O
+.	O
+,	O
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+,	O
+W	O
+.	O
+
+M	O
+.	O
+,	O
+and	O
+Weeks	O
+,	O
+C	O
+.	O
+
+E	O
+.	O
+
+The	O
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+
+weak	O
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+-	O
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+7	O
+,	O
+12	O
+-	O
+dimethylbenz	O
+(	O
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+(	O
+a	O
+)	O
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+-	O
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+.	O
+
+Cancer	O
+Lett	O
+.	O
+
+7	O
+:	O
+51	O
+-	O
+59	O
+(	O
+1979	O
+)	O
+.	O
+
+7	O
+.	O
+
+Topping	O
+,	O
+D	O
+.	O
+
+C	O
+.	O
+,	O
+Martin	O
+,	O
+D	O
+.	O
+
+H	O
+.	O
+,	O
+and	O
+Nettesheim	O
+,	O
+P	O
+.	O
+
+Determination	O
+of	O
+
+cocarcinogenic	O
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+(	O
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+)	O
+pyrene	O
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+respiratory	O
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+.	O
+
+Cancer	O
+Lett	O
+.	O
+
+11	O
+:	O
+315	O
+-	O
+321	O
+(	O
+1981	O
+)	O
+.	O
+
+8	O
+.	O
+
+Ilnitsky	O
+,	O
+A	O
+.	O
+
+P	O
+.	O
+,	O
+Voronin	O
+,	O
+V	O
+.	O
+
+M	O
+.	O
+,	O
+and	O
+Solenova	O
+,	O
+M	O
+.	O
+
+G	O
+.	O
+
+Carcinogenic	O
+effect	O
+
+of	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+and	O
+its	O
+combinations	O
+with	O
+other	O
+carbohydrates	O
+at	O
+their	O
+oral	O
+intake	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Voprosy	O
+Onkol	O
+.	O
+
+10	O
+:	O
+71	O
+-	O
+75	O
+(	O
+1974	O
+)	O
+.	O
+
+9	O
+.	O
+
+Kurljandsky	O
+,	O
+B	O
+.	O
+
+A	O
+.	O
+,	O
+Medvedovsky	O
+,	O
+A	O
+.	O
+
+G	O
+.	O
+,	O
+and	O
+Mashbits	O
+,	O
+F	O
+.	O
+
+D	O
+.	O
+
+On	O
+
+cocarcinogenic	O
+effect	O
+of	O
+toxic	O
+factors	O
+of	O
+low	O
+intensity	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+10	O
+:	O
+83	O
+-	O
+85	O
+(	O
+1972	O
+)	O
+.	O
+
+10	O
+.	O
+
+Thrusov	O
+,	O
+V	O
+.	O
+
+S	O
+.	O
+,	O
+and	O
+Andrianov	O
+,	O
+L	O
+.	O
+
+A	O
+.	O
+
+On	O
+combined	O
+effect	O
+on	O
+the	O
+skin	O
+of	O
+
+single	O
+application	O
+of	O
+7	O
+,	O
+12	O
+-	O
+dimethylbenz	O
+(	O
+a	O
+)	O
+anthracene	O
+and	O
+repeated	O
+applications	O
+of	O
+benz	O
+(	O
+a	O
+)	O
+pyrene	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Bull	O
+.	O
+
+Eksper	O
+.	O
+
+Biol	O
+.	O
+
+Med	O
+.	O
+
+3	O
+:	O
+80	O
+-	O
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+(	O
+1972	O
+)	O
+.	O
+
+11	O
+.	O
+
+Yanysheva	O
+,	O
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+.	O
+
+Ya	O
+.	O
+,	O
+Chernichenko	O
+,	O
+I	O
+.	O
+
+A	O
+.	O
+,	O
+Balenko	O
+,	O
+N	O
+.	O
+
+V	O
+,	O
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+Kireeva	O
+,	O
+
+I	O
+.	O
+
+S	O
+.	O
+
+Carcinogenic	O
+substances	O
+and	O
+their	O
+hygienic	O
+standardization	O
+in	O
+the	O
+environment	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Zdorovja	O
+,	O
+Kiev	O
+,	O
+1977	O
+.	O
+
+12	O
+.	O
+
+Laskin	O
+,	O
+S	O
+.	O
+,	O
+Kushner	O
+,	O
+M	O
+.	O
+,	O
+and	O
+Drew	O
+,	O
+R	O
+.	O
+
+T	O
+.	O
+
+Studies	O
+in	O
+pulmonary	O
+
+careinogenesis	O
+.	O
+
+In	O
+:	O
+Inhalation	O
+Carcinogenesis	O
+(	O
+M	O
+.	O
+G	O
+.	O
+Hanna	O
+,	O
+P	O
+.	O
+Nettesheim	O
+,	O
+and	O
+J	O
+.	O
+R	O
+.	O
+Gillbert	O
+,	O
+Eds	O
+.	O
+)	O
+U	O
+.	O
+S	O
+.	O
+
+Atomic	O
+Energy	O
+Commission	O
+Symposium	O
+,	O
+Series	O
+18	O
+,	O
+1970	O
+,	O
+p	O
+.	O
+
+321	O
+.	O
+
+13	O
+.	O
+
+Laskin	O
+,	O
+S	O
+.	O
+,	O
+Kuschner	O
+,	O
+M	O
+.	O
+,	O
+and	O
+Drew	O
+,	O
+R	O
+.	O
+
+T	O
+.	O
+
+Inhalation	O
+exposure	O
+to	O
+
+sulphur	O
+dioxide	O
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+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+.	O
+
+Oak	O
+Ridge	O
+National	O
+Laboratory	O
+,	O
+Gatlinburg	O
+,	O
+TN	O
+,	O
+1970	O
+,	O
+pp	O
+.	O
+
+322	O
+-	O
+351	O
+.	O
+
+14	O
+.	O
+
+Kuschner	O
+,	O
+M	O
+.	O
+,	O
+and	O
+Laskin	O
+,	O
+S	O
+.	O
+
+Experimental	O
+models	O
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+
+carcinogenesis	O
+.	O
+
+Am	O
+.	O
+
+J	O
+.	O
+
+Pathol	O
+.	O
+
+1	O
+:	O
+183	O
+-	O
+196	O
+(	O
+1971	O
+)	O
+.	O
+
+15	O
+.	O
+
+Komine	O
+,	O
+T	O
+.	O
+
+Influences	O
+of	O
+sulfur	O
+dioxide	O
+and	O
+3	O
+,	O
+4	O
+-	O
+benzpyrene	O
+on	O
+the	O
+
+respiratory	O
+organ	O
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+rats	B
+.	O
+
+Hokkaido	O
+Igaku	O
+Zasshi	O
+3	O
+:	O
+189	O
+-	O
+203	O
+(	O
+1977	O
+)	O
+.	O
+
+16	O
+.	O
+
+Skvortsova	O
+,	O
+N	O
+.	O
+
+N	O
+.	O
+
+Role	O
+of	O
+some	O
+common	O
+atmospheric	O
+pollutions	O
+in	O
+
+lung	O
+blastomogenesis	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+In	O
+:	O
+Handbook	O
+of	O
+Hygiene	O
+of	O
+Atmospheric	O
+Air	O
+(	O
+K	O
+.	O
+A	O
+.	O
+Bushtueva	O
+,	O
+Ed	O
+.	O
+)	O
+,	O
+Meditsina	O
+,	O
+Moscow	O
+,	O
+1976	O
+,	O
+pp	O
+.	O
+
+384	O
+-	O
+391	O
+.	O
+
+17	O
+.	O
+
+Yanysheva	O
+,	O
+N	O
+.	O
+
+Ya	O
+.	O
+,	O
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+,	O
+N	O
+.	O
+
+V	O
+,	O
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+,	O
+I	O
+.	O
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+A	O
+,	O
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+,	O
+V	O
+.	O
+
+F	O
+.	O
+
+Quantitation	O
+of	O
+modified	O
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+of	O
+nitrogen	O
+oxides	O
+on	O
+carcinogenicity	O
+of	O
+benz	O
+(	O
+a	O
+)	O
+pyrene	O
+effect	O
+[	O
+in	O
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+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+7	O
+:	O
+7	O
+-	O
+9	O
+(	O
+1986	O
+)	O
+.	O
+
+18	O
+.	O
+
+Yanysheva	O
+,	O
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+Ya	O
+.	O
+,	O
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+,	O
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+.	O
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+V	O
+.	O
+,	O
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+,	O
+I	O
+.	O
+
+A	O
+.	O
+,	O
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+,	O
+V	O
+.	O
+
+F	O
+.	O
+,	O
+
+Bakanova	O
+,	O
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+.	O
+
+N	O
+.	O
+,	O
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+Lemeshko	O
+,	O
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+.	O
+
+P	O
+.	O
+
+Peculiarities	O
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+manifestation	O
+of	O
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+combined	O
+effect	O
+of	O
+benz	O
+(	O
+a	O
+)	O
+pyrene	O
+and	O
+phenol	O
+depending	O
+on	O
+regimen	O
+of	O
+intake	O
+into	O
+the	O
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+[	O
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+Russian	O
+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+4	O
+:	O
+29	O
+-	O
+33	O
+(	O
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+)	O
+.	O
+
+19	O
+.	O
+
+Van	O
+Duuren	O
+,	O
+B	O
+.	O
+
+L	O
+.	O
+,	O
+Katz	O
+,	O
+C	O
+.	O
+,	O
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+Goldschmidt	O
+,	O
+B	O
+.	O
+
+M	O
+.	O
+
+Brief	O
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+
+tion	O
+:	O
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+agents	O
+in	O
+tobacco	B
+carcinogenesis	O
+.	O
+
+J	O
+.	O
+
+Natl	O
+.	O
+
+Cancer	O
+Inst	O
+.	O
+
+51	O
+:	O
+703	O
+-	O
+705	O
+(	O
+1973	O
+)	O
+.	O
+
+20	O
+.	O
+
+Van	O
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+,	O
+B	O
+.	O
+
+L	O
+.	O
+,	O
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+Goldschmidt	O
+,	O
+B	O
+.	O
+
+M	O
+.	O
+
+Cocarcinogenic	O
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+
+tumor	O
+-	O
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+.	O
+
+J	O
+.	O
+
+Natl	O
+.	O
+
+Cancer	O
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+.	O
+
+56	O
+:	O
+1237	O
+-	O
+1242	O
+(	O
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+)	O
+.	O
+
+21	O
+.	O
+
+Wattenberg	O
+,	O
+L	O
+.	O
+
+W	O
+.	O
+,	O
+Coccia	O
+,	O
+J	O
+.	O
+
+B	O
+.	O
+,	O
+and	O
+Lam	O
+,	O
+L	O
+.	O
+
+K	O
+.	O
+
+Inhibitory	O
+effects	O
+of	O
+
+phenolic	O
+compounds	O
+on	O
+benzo	O
+(	O
+a	O
+)	O
+pyrene	O
+-	O
+induced	O
+neoplasia	O
+.	O
+
+Cancer	O
+Res	O
+.	O
+
+8	O
+:	O
+2820	O
+-	O
+2823	O
+(	O
+1980	O
+)	O
+.	O
+
+22	O
+.	O
+
+Bogovski	O
+,	O
+P	O
+.	O
+
+A	O
+,	O
+and	O
+Mirme	O
+,	O
+H	O
+.	O
+
+Yu	O
+.	O
+
+Cocarcinogenicity	O
+of	O
+phenols	O
+from	O
+
+Estonian	O
+shale	O
+tars	O
+(	O
+oils	O
+)	O
+.	O
+
+Environ	O
+.	O
+
+Health	O
+Perspect	O
+.	O
+
+30	O
+:	O
+177	O
+-	O
+178	O
+(	O
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+)	O
+.	O
+
+23	O
+.	O
+
+Gubergritz	O
+,	O
+M	O
+.	O
+
+Ya	O
+.	O
+,	O
+and	O
+Kirso	O
+,	O
+U	O
+.	O
+
+E	O
+.	O
+
+Carcinogenic	O
+properties	O
+,	O
+struc	O
+
+ture	O
+and	O
+reactive	O
+capacity	O
+of	O
+phenols	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Voprosy	O
+Onkol	O
+.	O
+
+8	O
+:	O
+96	O
+-	O
+100	O
+(	O
+1970	O
+)	O
+.	O
+
+24	O
+.	O
+
+Mirme	O
+,	O
+H	O
+.	O
+
+Yu	O
+.	O
+
+Modifying	O
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+of	O
+water	O
+-	O
+soluble	O
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+phenols	O
+upon	O
+
+carcinogenesis	O
+[	O
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+Russian	O
+]	O
+.	O
+
+In	O
+:	O
+Problems	O
+of	O
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+of	O
+Pollution	O
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+by	O
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+(	O
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+.	O
+M	O
+.	O
+Shabad	O
+,	O
+Ed	O
+.	O
+)	O
+,	O
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+,	O
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+,	O
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+,	O
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+.	O
+
+16	O
+-	O
+18	O
+.	O
+
+25	O
+.	O
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+Kirso	O
+,	O
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+.	O
+
+E	O
+.	O
+,	O
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+,	O
+Yu	O
+.	O
+
+V	O
+.	O
+,	O
+Bakhitova	O
+,	O
+L	O
+.	O
+
+M	O
+.	O
+,	O
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+Kjung	O
+,	O
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+.	O
+
+I	O
+.	O
+
+Effect	O
+
+of	O
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+(	O
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+)	O
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+
+Voprosy	O
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+.	O
+
+4	O
+:	O
+70	O
+-	O
+75	O
+(	O
+1985	O
+)	O
+.	O
+
+26	O
+.	O
+
+Veldre	O
+,	O
+I	O
+.	O
+
+A	O
+.	O
+
+Comparative	O
+assessment	O
+of	O
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+effect	O
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+some	O
+water	O
+
+soluble	O
+phenols	O
+[	O
+in	O
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+]	O
+.	O
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+In	O
+:	O
+Proceedings	O
+of	O
+the	O
+Scientific	O
+Conference	O
+on	O
+Urgent	O
+Problems	O
+Related	O
+with	O
+Decrease	O
+of	O
+Infectious	O
+Diseases	O
+Morbidity	O
+and	O
+with	O
+Hygienic	O
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+.	O
+
+Tallinn	O
+,	O
+1968	O
+,	O
+pp	O
+.	O
+
+200	O
+-	O
+202	O
+.	O
+
+27	O
+.	O
+
+Substances	O
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+.	O
+
+In	O
+:	O
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+stances	O
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+(	O
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+.	O
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+A	O
+.	O
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+.	O
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+,	O
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+.	O
+)	O
+,	O
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+,	O
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+,	O
+pp	O
+.	O
+
+111	O
+-	O
+113	O
+.	O
+
+28	O
+.	O
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+Djatlovitskaya	O
+,	O
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+.	O
+
+G	O
+.	O
+,	O
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+Maktas	O
+,	O
+E	O
+.	O
+
+D	O
+.	O
+
+Separate	O
+determination	O
+of	O
+fly	O
+
+phenols	O
+in	O
+water	O
+using	O
+thin	O
+-	O
+layer	O
+chromatography	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+6	O
+:	O
+60	O
+-	O
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+(	O
+1965	O
+)	O
+.	O
+
+29	O
+.	O
+
+Kostovetsky	O
+,	O
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+.	O
+
+I	O
+.	O
+,	O
+and	O
+Zholdakova	O
+,	O
+Z	O
+.	O
+
+I	O
+.	O
+
+About	O
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+rate	O
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+
+of	O
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+in	O
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+[	O
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+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+7	O
+:	O
+7	O
+-	O
+10	O
+(	O
+1971	O
+)	O
+.	O
+
+30	O
+.	O
+
+Mostkovoy	O
+,	O
+M	O
+.	O
+
+I	O
+.	O
+
+Practicum	O
+on	O
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+-	O
+statistical	O
+processing	O
+of	O
+
+clinical	O
+material	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Ashkhabad	O
+,	O
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+,	O
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+.	O
+
+132	O
+.	O
+
+31	O
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+Weinstein	O
+,	O
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+
+B	O
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+
+The	O
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+
+primary	O
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+prevention	O
+.	O
+
+Cancer	O
+47	O
+:	O
+1133	O
+-	O
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+(	O
+1981	O
+)	O
+.	O
+
+32	O
+.	O
+
+Merkulov	O
+,	O
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+.	O
+
+I	O
+,	O
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+,	O
+R	O
+.	O
+
+I	O
+.	O
+
+About	O
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+effect	O
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+[	O
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+
+Russian	O
+]	O
+.	O
+
+Gig	O
+.	O
+
+Sanit	O
+.	O
+
+1	O
+:	O
+79	O
+-	O
+80	O
+(	O
+1984	O
+)	O
+.	O
+
+33	O
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+Weinstein	O
+,	O
+I	O
+.	O
+
+B	O
+.	O
+,	O
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+,	O
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+
+A	O
+.	O
+,	O
+Lee	O
+,	O
+L	O
+.	O
+
+S	O
+.	O
+,	O
+et	O
+al	O
+.	O
+
+Membrane	O
+and	O
+other	O
+
+biochemical	O
+effects	O
+of	O
+the	O
+phorbol	O
+esters	O
+and	O
+their	O
+relevance	O
+to	O
+tumor	O
+promotion	O
+.	O
+
+In	O
+:	O
+Carcinogenesis	O
+.	O
+
+Fundamental	O
+Mechanisms	O
+and	O
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+Effects	O
+.	O
+
+London	O
+,	O
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+,	O
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+.	O
+
+543	O
+-	O
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+.	O
+
+34	O
+.	O
+
+Yamasaki	O
+,	O
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+.	O
+,	O
+and	O
+Weinstein	O
+,	O
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+.	O
+
+B	O
+.	O
+
+Cellular	O
+and	O
+molecular	O
+mecha	O
+
+nisms	O
+of	O
+tumor	O
+promotion	O
+and	O
+their	O
+implications	O
+for	O
+risk	O
+assessment	O
+.	O
+
+In	O
+:	O
+Methods	O
+for	O
+Estimating	O
+Risk	O
+of	O
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+Injury	O
+:	O
+Human	B
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+Non	O
+-	O
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+(	O
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+.	O
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+.	O
+Vouk	O
+,	O
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+.	O
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+.	O
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+,	O
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+.	O
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+.	O
+Hoel	O
+,	O
+and	O
+D	O
+.	O
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+.	O
+Peakall	O
+,	O
+Eds	O
+.	O
+)	O
+,	O
+SCOPE	O
+,	O
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+,	O
+pp	O
+.	O
+
+155	O
+-	O
+180	O
+.	O
+
+35	O
+.	O
+
+Karu	O
+,	O
+T	O
+,	O
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+,	O
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+.	O
+
+E	O
+.	O
+,	O
+and	O
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+,	O
+L	O
+.	O
+
+A	O
+.	O
+
+Dynamics	O
+of	O
+resorption	O
+of	O
+
+3	O
+,	O
+4	O
+-	O
+benzpyrene	O
+with	O
+phenols	O
+from	O
+mouse	B
+skin	O
+[	O
+in	O
+Russian	O
+]	O
+.	O
+
+Voprosy	O
+Onkol	O
+.	O
+
+5	O
+:	O
+80	O
+-	O
+84	O
+(	O
+1973	O
+)	O
+.	O
+
+36	O
+.	O
+
+Yanysheva	O
+,	O
+N	O
+.	O
+
+Ya	O
+.	O
+,	O
+Yurkovskaya	O
+,	O
+T	O
+.	O
+
+N	O
+.	O
+,	O
+Beregovskaya	O
+,	O
+N	O
+.	O
+
+N	O
+.	O
+,	O
+et	O
+al	O
+.	O
+
+Metalloenzymic	O
+complexes	O
+of	O
+energetic	O
+and	O
+detoxicating	O
+systems	O
+of	O
+cell	O
+during	O
+benz	O
+(	O
+a	O
+)	O
+pyrene	O
+-	O
+induced	O
+carcinogenesis	O
+.	O
+
+In	O
+:	O
+Proceedings	O
+of	O
+the	O
+4th	O
+National	O
+Congress	O
+of	O
+Oncology	O
+with	O
+International	O
+Participation	O
+.	O
+
+Sofia	O
+,	O
+1985	O
+,	O
+p	O
+.	O
+
+102	O
+.	O
+
+37	O
+.	O
+
+Mizell	O
+,	O
+M	O
+.	O
+
+Anuran	O
+(	O
+Lucke	O
+)	O
+tumor	O
+breakdown	O
+in	O
+regenerating	O
+anuran	O
+
+tadpole	O
+tails	O
+.	O
+
+Anat	O
+.	O
+
+Res	O
+.	O
+
+137	O
+:	O
+382	O
+-	O
+383	O
+(	O
+1960	O
+)	O
+.	O
+
+38	O
+.	O
+
+Sheremetieva	O
+,	O
+E	O
+.	O
+
+N	O
+.	O
+
+Spontaneous	O
+melanoma	O
+in	O
+regenerating	O
+tails	O
+of	O
+
+axolotis	O
+.	O
+
+J	O
+.	O
+
+Exp	O
+.	O
+
+Zool	O
+.	O
+
+158	O
+:	O
+101	O
+-	O
+122	O
+(	O
+1965	O
+)	O
+.	O
+
+39	O
+.	O
+
+Tsonis	O
+,	O
+P	O
+.	O
+
+A	O
+,	O
+and	O
+Eguchi	O
+,	O
+G	O
+.	O
+
+Carcinogens	O
+on	O
+regeneration	O
+.	O
+
+Effects	O
+on	O
+
+N	O
+-	O
+methyl	O
+-	O
+N	O
+-	O
+nitro	O
+-	O
+N	O
+-	O
+nitrosoguanidine	O
+and	O
+4	O
+-	O
+nitrogninoline	O
+-	O
+1	O
+-	O
+oxide	O
+on	O
+limb	O
+regeneration	O
+in	O
+adult	O
+newts	O
+.	O
+
+Differentiation	O
+20	O
+:	O
+52	O
+-	O
+60	O
+(	O
+1981	O
+)	O
+.	O
+
+B	O
+lymphocyte	O
+stimulator	O
+(	O
+BLyS	O
+)	O
+isoforms	O
+in	O
+systemic	O
+lupus	O
+erythematosus	O
+:	O
+disease	O
+activity	O
+correlates	O
+better	O
+with	O
+blood	O
+leukocyte	O
+BLyS	O
+mRNA	O
+levels	O
+than	O
+with	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+
+Abstract	O
+
+Considerable	O
+evidence	O
+points	O
+to	O
+a	O
+role	O
+for	O
+B	O
+lymphocyte	O
+stimulator	O
+(	O
+BLyS	O
+)	O
+overproduction	O
+in	O
+murine	B
+and	O
+human	B
+systemic	O
+lupus	O
+erythematosus	O
+(	O
+SLE	O
+)	O
+.	O
+
+Nevertheless	O
+,	O
+the	O
+correlation	O
+between	O
+circulating	O
+levels	O
+of	O
+BLyS	O
+protein	O
+and	O
+disease	O
+activity	O
+in	O
+human	B
+SLE	O
+is	O
+modest	O
+at	O
+best	O
+.	O
+
+This	O
+may	O
+be	O
+due	O
+to	O
+an	O
+inadequacy	O
+of	O
+the	O
+former	O
+to	O
+reflect	O
+endogenous	O
+BLyS	O
+overproduction	O
+faithfully	O
+,	O
+in	O
+that	O
+steady	O
+-	O
+state	O
+protein	O
+levels	O
+are	O
+affected	O
+not	O
+just	O
+by	O
+production	O
+rates	O
+but	O
+also	O
+by	O
+rates	O
+of	O
+peripheral	O
+utilization	O
+and	O
+excretion	O
+.	O
+
+Increased	O
+levels	O
+of	O
+BLyS	O
+mRNA	O
+may	O
+better	O
+reflect	O
+increased	O
+in	O
+vivo	O
+BLyS	O
+production	O
+,	O
+and	O
+therefore	O
+they	O
+may	O
+correlate	O
+better	O
+with	O
+biologic	O
+and	O
+clinical	O
+sequelae	O
+of	O
+BLyS	O
+overexpression	O
+than	O
+do	O
+circulating	O
+levels	O
+of	O
+BLyS	O
+protein	O
+.	O
+
+Accordingly	O
+,	O
+we	O
+assessed	O
+peripheral	O
+blood	O
+leukocyte	O
+levels	O
+of	O
+BLyS	O
+mRNA	O
+isoforms	O
+(	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+)	O
+and	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+in	O
+patients	B
+with	O
+SLE	O
+,	O
+and	O
+correlated	O
+these	O
+levels	O
+with	O
+laboratory	O
+and	O
+clinical	O
+features	O
+.	O
+
+BLyS	O
+protein	O
+,	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+,	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+greater	O
+in	O
+SLE	O
+patients	B
+(	O
+n	O
+=	O
+60	O
+)	O
+than	O
+in	O
+rheumatoid	O
+arthritis	O
+patients	B
+(	O
+n	O
+=	O
+60	O
+)	O
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+normal	O
+control	O
+individuals	O
+(	O
+n	O
+=	O
+30	O
+)	O
+.	O
+
+Although	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+correlated	O
+significantly	O
+with	O
+BLyS	O
+protein	O
+levels	O
+in	O
+the	O
+SLE	O
+cohort	O
+,	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+more	O
+closely	O
+associated	O
+with	O
+serum	O
+immunoglobulin	O
+levels	O
+and	O
+SLE	O
+Disease	O
+Activity	O
+Index	O
+scores	O
+than	O
+were	O
+BLyS	O
+protein	O
+levels	O
+.	O
+
+Moreover	O
+,	O
+changes	O
+in	O
+SLE	O
+Disease	O
+Activity	O
+Index	O
+scores	O
+were	O
+more	O
+closely	O
+associated	O
+with	O
+changes	O
+in	O
+BLyS	O
+mRNA	O
+levels	O
+than	O
+with	O
+changes	O
+in	O
+BLyS	O
+protein	O
+levels	O
+among	O
+the	O
+37	O
+SLE	O
+patients	B
+from	O
+whom	O
+repeat	O
+blood	O
+samples	O
+were	O
+obtained	O
+.	O
+
+Thus	O
+,	O
+full	O
+-	O
+length	O
+BLyS	O
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+Delta	O
+BLyS	O
+mRNA	O
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+in	O
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+and	O
+are	O
+more	O
+closely	O
+associated	O
+with	O
+disease	O
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+than	O
+are	O
+BLyS	O
+protein	O
+levels	O
+.	O
+
+BLyS	O
+mRNA	O
+levels	O
+may	O
+be	O
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+helpful	O
+biomarker	O
+in	O
+the	O
+clinical	O
+monitoring	O
+of	O
+SLE	O
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+.	O
+
+Introduction	O
+
+B	O
+lymphocyte	O
+stimulator	O
+(	O
+BLyS	O
+;	O
+a	O
+trademark	O
+of	O
+Human	B
+Genome	O
+Sciences	O
+,	O
+Inc	O
+.	O
+,	O
+Rockville	O
+,	O
+MD	O
+,	O
+USA	O
+)	O
+is	O
+a	O
+285	O
+-	O
+amino	O
+-	O
+acid	O
+member	O
+of	O
+the	O
+tumor	O
+necrosis	O
+factor	O
+ligand	O
+superfamily	O
+[	O
+1	O
+-	O
+3	O
+]	O
+.	O
+
+A	O
+causal	O
+relation	O
+between	O
+constitutive	O
+overproduction	O
+of	O
+BLyS	O
+and	O
+development	O
+of	O
+systemic	O
+lupus	O
+erythematosus	O
+(	O
+SLE	O
+)	O
+-	O
+like	O
+illness	O
+has	O
+incontrovertibly	O
+been	O
+established	O
+in	O
+mice	B
+.	O
+
+BLyS	O
+-	O
+transgenic	O
+mice	B
+often	O
+develop	O
+SLE	O
+-	O
+like	O
+features	O
+as	O
+they	O
+age	O
+[	O
+3	O
+-	O
+5	O
+]	O
+,	O
+and	O
+SLE	O
+-	O
+prone	O
+(	O
+NZB	O
+x	O
+NZW	O
+)	O
+F1	O
+(	O
+BWF1	O
+)	O
+and	O
+MRL	O
+-	O
+lpr	O
+/	O
+lpr	O
+mice	B
+respond	O
+clinically	O
+to	O
+treatment	O
+with	O
+BLyS	O
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+(	O
+decreased	O
+disease	O
+progression	O
+and	O
+improved	O
+survival	O
+)	O
+[	O
+3	O
+,	O
+6	O
+]	O
+.	O
+
+Considerable	O
+inferential	O
+evidence	O
+points	O
+to	O
+a	O
+role	O
+for	O
+BLyS	O
+overproduction	O
+in	O
+human	B
+SLE	O
+as	O
+well	O
+.	O
+
+Cross	O
+-	O
+sectional	O
+studies	O
+have	O
+demonstrated	O
+elevated	O
+circulating	O
+levels	O
+of	O
+BLyS	O
+in	O
+20	O
+-	O
+30	O
+%	O
+of	O
+human	B
+SLE	O
+patients	B
+tested	O
+at	O
+a	O
+single	O
+point	O
+in	O
+time	O
+[	O
+7	O
+,	O
+8	O
+]	O
+.	O
+
+Moreover	O
+,	O
+a	O
+12	O
+-	O
+month	O
+longitudinal	O
+study	O
+documented	O
+persistently	O
+elevated	O
+serum	O
+BLyS	O
+levels	O
+in	O
+about	O
+25	O
+%	O
+of	O
+SLE	O
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+and	O
+intermittently	O
+elevated	O
+serum	O
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+levels	O
+in	O
+an	O
+additional	O
+25	O
+%	O
+of	O
+patients	B
+[	O
+9	O
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+.	O
+
+Remarkably	O
+,	O
+circulating	O
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+not	O
+correlate	O
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+disease	O
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+(	O
+measured	O
+using	O
+the	O
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+Disease	O
+Activity	O
+Index	O
+[	O
+SLEDAI	O
+]	O
+)	O
+in	O
+these	O
+cross	O
+-	O
+sectional	O
+or	O
+longitudinal	O
+studies	O
+[	O
+7	O
+-	O
+9	O
+]	O
+.	O
+
+Although	O
+a	O
+statistically	O
+significant	O
+correlation	O
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+circulating	O
+BLyS	O
+levels	O
+and	O
+SLEDAI	O
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+been	O
+appreciated	O
+in	O
+a	O
+more	O
+recent	O
+24	O
+-	O
+month	O
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+study	O
+of	O
+245	O
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+(	O
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+>	O
+1	O
+,	O
+700	O
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+analyzed	O
+)	O
+[	O
+10	O
+]	O
+,	O
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+remains	O
+weak	O
+.	O
+
+The	O
+limited	O
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+between	O
+circulating	O
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+disease	O
+activity	O
+in	O
+these	O
+studies	O
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+have	O
+exposed	O
+an	O
+inadequacy	O
+of	O
+the	O
+former	O
+to	O
+reflect	O
+faithfully	O
+endogenous	O
+BLyS	O
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+.	O
+
+In	O
+addition	O
+to	O
+the	O
+rate	O
+of	O
+BLyS	O
+protein	O
+production	O
+,	O
+several	O
+other	O
+factors	O
+(	O
+for	O
+example	O
+,	O
+utilization	O
+and	O
+excretion	O
+)	O
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+affect	O
+circulating	O
+BLyS	O
+protein	O
+levels	O
+.	O
+
+Although	O
+there	O
+are	O
+no	O
+practicable	O
+means	O
+of	O
+directly	O
+measuring	O
+in	O
+vivo	O
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+se	O
+in	O
+humans	B
+,	O
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+marker	O
+of	O
+in	O
+vivo	O
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+production	O
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+does	O
+the	O
+level	O
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+BLyS	O
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+.	O
+
+Candidate	O
+BLyS	O
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+include	O
+the	O
+full	O
+-	O
+length	O
+BLyS	O
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+isoform	O
+,	O
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+encodes	O
+the	O
+full	O
+-	O
+length	O
+protein	O
+,	O
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+the	O
+alternatively	O
+spliced	O
+Delta	O
+BLyS	O
+mRNA	O
+isoform	O
+,	O
+which	O
+encodes	O
+a	O
+protein	O
+with	O
+a	O
+small	O
+peptide	O
+deletion	O
+[	O
+11	O
+]	O
+.	O
+
+(	O
+Delta	O
+BLyS	O
+does	O
+not	O
+bind	O
+to	O
+cells	O
+expressing	O
+BLyS	O
+receptors	O
+,	O
+and	O
+therefore	O
+it	O
+has	O
+no	O
+agonistic	O
+activity	O
+.	O
+Moreover	O
+,	O
+Delta	O
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+can	O
+form	O
+heterotrimers	O
+with	O
+full	O
+-	O
+length	O
+BLyS	O
+,	O
+thereby	O
+actually	O
+functioning	O
+as	O
+a	O
+dominant	O
+-	O
+negative	O
+antagonist	O
+of	O
+BLyS	O
+activity	O
+.	O
+)	O
+
+In	O
+this	O
+report	O
+we	O
+demonstrate	O
+that	O
+peripheral	O
+blood	O
+leukocytes	O
+from	O
+SLE	O
+patients	B
+express	O
+elevated	O
+mRNA	O
+levels	O
+of	O
+both	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+relative	O
+to	O
+those	O
+levels	O
+expressed	O
+by	O
+patients	B
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+rheumatoid	O
+arthritis	O
+(	O
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+)	O
+or	O
+by	O
+normal	O
+control	O
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+.	O
+
+In	O
+the	O
+SLE	O
+patients	B
+,	O
+both	O
+full	O
+-	O
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+BLyS	O
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+BLyS	O
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+more	O
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+associated	O
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+disease	O
+activity	O
+(	O
+SLEDAI	O
+)	O
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+are	O
+BLyS	O
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+levels	O
+.	O
+
+Accordingly	O
+,	O
+BLyS	O
+mRNA	O
+levels	O
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+helpful	O
+biomarker	O
+in	O
+the	O
+clinical	O
+monitoring	O
+of	O
+SLE	O
+patients	B
+.	O
+
+Materials	O
+and	O
+methods	O
+
+General	O
+details	O
+
+This	O
+study	O
+was	O
+approved	O
+by	O
+the	O
+institutional	O
+review	O
+boards	O
+of	O
+the	O
+University	O
+of	O
+Southern	O
+California	O
+and	O
+the	O
+Scripps	O
+Research	O
+Institute	O
+.	O
+
+All	O
+participants	B
+gave	O
+their	O
+written	O
+informed	O
+consent	O
+before	O
+participation	O
+in	O
+this	O
+study	O
+.	O
+
+Participants	B
+
+Patients	B
+receiving	O
+outpatient	O
+medical	O
+care	O
+at	O
+the	O
+rheumatology	O
+clinics	O
+of	O
+the	O
+Los	O
+Angeles	O
+County	O
++	O
+University	O
+of	O
+Southern	O
+California	O
+Medical	O
+Center	O
+were	O
+recruited	O
+into	O
+the	O
+study	O
+.	O
+
+Diagnoses	O
+of	O
+SLE	O
+(	O
+n	O
+=	O
+60	O
+)	O
+or	O
+RA	O
+(	O
+n	O
+=	O
+60	O
+)	O
+were	O
+based	O
+on	O
+established	O
+clinical	O
+criteria	O
+[	O
+12	O
+]	O
+.	O
+
+Healthy	O
+control	O
+individuals	O
+(	O
+n	O
+=	O
+30	O
+)	O
+were	O
+recruited	O
+from	O
+Los	O
+Angeles	O
+County	O
++	O
+University	O
+of	O
+Southern	O
+California	O
+Medical	O
+Center	O
+and	O
+University	O
+of	O
+Southern	O
+California	O
+Keck	O
+School	O
+of	O
+Medicine	O
+personnel	O
+.	O
+
+No	O
+exclusions	O
+were	O
+made	O
+on	O
+any	O
+basis	O
+other	O
+than	O
+an	O
+inability	O
+to	O
+give	O
+informed	O
+consent	O
+.	O
+
+Each	O
+patient	B
+'	O
+s	O
+sex	O
+,	O
+race	O
+,	O
+age	O
+,	O
+and	O
+medications	O
+at	O
+the	O
+time	O
+of	O
+the	O
+phlebotomy	O
+were	O
+recorded	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Based	O
+solely	O
+on	O
+the	O
+patient	B
+'	O
+s	O
+willingness	O
+to	O
+donate	O
+a	O
+second	O
+blood	O
+sample	O
+,	O
+repeat	O
+blood	O
+samples	O
+were	O
+collected	O
+from	O
+37	O
+of	O
+the	O
+SLE	O
+patients	B
+147	O
+-	O
+511	O
+days	O
+(	O
+median	O
+371	O
+days	O
+)	O
+after	O
+collection	O
+of	O
+the	O
+first	O
+samples	O
+.	O
+
+These	O
+patients	B
+were	O
+not	O
+selected	O
+on	O
+the	O
+basis	O
+of	O
+any	O
+demographic	O
+,	O
+clinical	O
+,	O
+or	O
+laboratory	O
+feature	O
+.	O
+
+Clinical	O
+disease	O
+activity	O
+for	O
+the	O
+SLE	O
+patients	B
+was	O
+assessed	O
+using	O
+the	O
+SLEDAI	O
+[	O
+13	O
+]	O
+and	O
+using	O
+a	O
+modified	O
+SLEDAI	O
+that	O
+excludes	O
+the	O
+contribution	O
+of	O
+anti	O
+-	O
+double	O
+-	O
+stranded	O
+DNA	O
+(	O
+anti	O
+-	O
+dsDNA	O
+)	O
+antibodies	O
+from	O
+the	O
+total	O
+score	O
+.	O
+
+Each	O
+patient	B
+'	O
+s	O
+medical	O
+chart	O
+was	O
+reviewed	O
+for	O
+results	O
+of	O
+standard	O
+clinical	O
+laboratory	O
+tests	O
+within	O
+the	O
+previous	O
+or	O
+subsequent	O
+1	O
+-	O
+month	O
+period	O
+.	O
+
+Plasma	O
+BLyS	O
+determination	O
+
+Whole	O
+venous	O
+blood	O
+was	O
+centrifuged	O
+to	O
+yield	O
+plasma	O
+and	O
+a	O
+buffy	O
+coat	O
+.	O
+
+The	O
+plasma	O
+was	O
+harvested	O
+,	O
+stored	O
+at	O
+-	O
+70	O
+degrees	O
+C	O
+,	O
+and	O
+assayed	O
+for	O
+BLyS	O
+levels	O
+by	O
+ELISA	O
+[	O
+8	O
+,	O
+14	O
+]	O
+using	O
+Fab	O
+fragments	O
+of	O
+the	O
+capture	O
+antibody	O
+rather	O
+than	O
+the	O
+whole	O
+antibody	O
+to	O
+reduce	O
+assay	O
+interference	O
+by	O
+rheumatoid	O
+factor	O
+.	O
+
+The	O
+lower	O
+limit	O
+of	O
+detection	O
+in	O
+this	O
+assay	O
+is	O
+0	O
+.	O
+3	O
+ng	O
+/	O
+ml	O
+.	O
+
+For	O
+statistical	O
+purposes	O
+,	O
+plasma	O
+samples	O
+with	O
+BLyS	O
+concentrations	O
+below	O
+the	O
+lower	O
+limit	O
+of	O
+detection	O
+were	O
+assigned	O
+a	O
+value	O
+of	O
+0	O
+.	O
+25	O
+ng	O
+/	O
+ml	O
+.	O
+
+Blood	O
+BLyS	O
+mRNA	O
+determination	O
+
+The	O
+buffy	O
+coat	O
+from	O
+centrifuged	O
+whole	O
+blood	O
+was	O
+harvested	O
+,	O
+added	O
+to	O
+RNAlater	O
+(	O
+TM	O
+)	O
+(	O
+Ambion	O
+,	O
+Austin	O
+,	O
+TX	O
+,	O
+USA	O
+)	O
+at	O
+a	O
+1	O
+:	O
+4	O
+vol	O
+/	O
+vol	O
+ratio	O
+for	O
+RNA	O
+stabilization	O
+,	O
+stored	O
+at	O
+-	O
+70	O
+degrees	O
+C	O
+,	O
+and	O
+assayed	O
+for	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+by	O
+real	O
+-	O
+time	O
+PCR	O
+.	O
+
+Total	O
+RNA	O
+was	O
+purified	O
+from	O
+buffy	O
+coat	O
+samples	O
+using	O
+RNAeasy	O
+miniprep	O
+kits	O
+(	O
+Qiagen	O
+,	O
+Valencia	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+,	O
+and	O
+contaminating	O
+genomic	O
+DNA	O
+was	O
+removed	O
+by	O
+DNAse	O
+-	O
+I	O
+digestion	O
+.	O
+
+One	O
+-	O
+tenth	O
+volume	O
+of	O
+total	O
+RNA	O
+was	O
+used	O
+as	O
+template	O
+in	O
+the	O
+first	O
+-	O
+strand	O
+cDNA	O
+reaction	O
+using	O
+oligo	O
+-	O
+dT	O
+and	O
+the	O
+Superscript	O
+III	O
+first	O
+-	O
+strand	O
+synthesis	O
+system	O
+(	O
+Invitrogen	O
+,	O
+Carlsbad	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+Duplicate	O
+samples	O
+of	O
+cDNA	O
+were	O
+amplified	O
+with	O
+primers	O
+against	O
+beta	O
+-	O
+actin	O
+,	O
+full	O
+-	O
+length	O
+BLyS	O
+,	O
+or	O
+Delta	O
+BLyS	O
+:	O
+beta	O
+-	O
+actin	O
+sense	O
+5	O
+'	O
+-	O
+CGAGAAGATGACCCAGATCA	O
+-	O
+3	O
+'	O
+;	O
+beta	O
+-	O
+actin	O
+anti	O
+-	O
+sense	O
+5	O
+'	O
+-	O
+GGCATACCCCTCGTAGATGG	O
+-	O
+3	O
+'	O
+;	O
+full	O
+-	O
+length	O
+BLyS	O
+sense	O
+5	O
+'	O
+-	O
+GCAGACAGTGAAACACCAAC	O
+-	O
+3	O
+'	O
+;	O
+Delta	O
+BLyS	O
+sense	O
+5	O
+'	O
+-	O
+CAGAAGAAACAGGATCTTAC	O
+-	O
+3	O
+'	O
+;	O
+and	O
+full	O
+-	O
+length	O
+BLyS	O
+/	O
+Delta	O
+BLyS	O
+anti	O
+-	O
+sense	O
+5	O
+'	O
+-	O
+TGCCAGCTGAATAGCAGGAA	O
+-	O
+3	O
+'	O
+.	O
+
+A	O
+165	O
+bp	O
+amplicon	O
+for	O
+beta	O
+-	O
+actin	O
+was	O
+PCR	O
+-	O
+amplified	O
+using	O
+the	O
+7900	O
+HT	O
+ABI	O
+Prism	O
+machine	O
+(	O
+Qiagen	O
+)	O
+with	O
+annealing	O
+at	O
+65	O
+degrees	O
+C	O
+.	O
+
+A	O
+296	O
+bp	O
+amplicon	O
+for	O
+full	O
+-	O
+length	O
+BLyS	O
+was	O
+PCR	O
+-	O
+amplified	O
+,	O
+with	O
+annealing	O
+at	O
+64	O
+degrees	O
+C	O
+.	O
+
+A	O
+270	O
+bp	O
+amplicon	O
+for	O
+Delta	O
+BLyS	O
+was	O
+PCR	O
+-	O
+amplified	O
+with	O
+annealing	O
+at	O
+61	O
+degrees	O
+C	O
+.	O
+
+The	O
+annealing	O
+conditions	O
+for	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+were	O
+determined	O
+so	O
+that	O
+each	O
+primer	O
+set	O
+remained	O
+specific	O
+to	O
+the	O
+respective	O
+BLyS	O
+isoform	O
+and	O
+yielded	O
+a	O
+PCR	O
+efficiency	O
+similar	O
+to	O
+those	O
+of	O
+cloned	O
+cDNA	O
+standards	O
+.	O
+
+Melting	O
+curve	O
+analysis	O
+revealed	O
+a	O
+single	O
+peak	O
+for	O
+each	O
+gene	O
+amplified	O
+.	O
+
+The	O
+threshold	O
+cycle	O
+(	O
+Ct	O
+)	O
+values	O
+for	O
+each	O
+reaction	O
+were	O
+determined	O
+using	O
+Sequence	O
+Detection	O
+System	O
+software	O
+(	O
+Applied	O
+Biosystems	O
+,	O
+Foster	O
+City	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+Results	O
+are	O
+presented	O
+as	O
+ratios	O
+of	O
+full	O
+-	O
+length	O
+BLyS	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+to	O
+beta	O
+-	O
+actin	O
+mRNA	O
+,	O
+which	O
+were	O
+calculated	O
+using	O
+the	O
+following	O
+formulae	O
+:	O
+
+2	O
+exp	O
+(	O
+Ct	O
+beta	O
+-	O
+actin	O
+-	O
+Ctfull	O
+-	O
+length	O
+BLyS	O
+)	O
+
+2	O
+exp	O
+(	O
+Ct	O
+beta	O
+-	O
+actin	O
+-	O
+Ct	O
+Delta	O
+BLyS	O
+)	O
+
+Determination	O
+of	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+
+BLyS	O
+was	O
+bound	O
+to	O
+microtiter	O
+plates	O
+by	O
+first	O
+coating	O
+the	O
+plates	O
+with	O
+streptavidin	O
+and	O
+then	O
+adding	O
+biotinylated	O
+recombinant	O
+BLyS	O
+.	O
+
+Using	O
+these	O
+plates	O
+as	O
+the	O
+capture	O
+reagent	O
+,	O
+plasma	O
+samples	O
+were	O
+incubated	O
+,	O
+and	O
+horseradish	B
+peroxidase	O
+-	O
+conjugated	O
+anti	O
+-	O
+human	B
+IgA	O
+/	O
+IgM	O
+/	O
+IgG	O
+(	O
+Southern	O
+Biotechnology	O
+Associates	O
+,	O
+Birmingham	O
+,	O
+AL	O
+,	O
+USA	O
+;	O
+1	O
+:	O
+20	O
+,	O
+000	O
+final	O
+dilution	O
+)	O
+or	O
+horseradish	B
+peroxidase	O
+-	O
+conjugated	O
+anti	O
+-	O
+human	B
+IgG	O
+(	O
+Southern	O
+Biotechnology	O
+;	O
+1	O
+:	O
+10	O
+,	O
+000	O
+final	O
+dilution	O
+)	O
+were	O
+used	O
+as	O
+the	O
+detector	O
+reagents	O
+.	O
+
+Statistical	O
+analysis	O
+
+All	O
+analyses	O
+were	O
+performed	O
+using	O
+SigmaStat	O
+software	O
+(	O
+SPSS	O
+,	O
+Chicago	O
+,	O
+IL	O
+,	O
+USA	O
+)	O
+.	O
+
+Results	O
+that	O
+did	O
+not	O
+follow	O
+a	O
+normal	O
+distribution	O
+were	O
+log	O
+-	O
+transformed	O
+to	O
+achieve	O
+normality	O
+.	O
+
+Parametric	O
+testing	O
+between	O
+two	O
+matched	O
+or	O
+unmatched	O
+groups	O
+was	O
+performed	O
+using	O
+the	O
+paired	O
+or	O
+unpaired	O
+t	O
+test	O
+,	O
+respectively	O
+.	O
+
+Parametric	O
+testing	O
+among	O
+three	O
+or	O
+more	O
+groups	O
+was	O
+performed	O
+using	O
+one	O
+-	O
+way	O
+analysis	O
+of	O
+variance	O
+.	O
+
+When	O
+log	O
+-	O
+transformation	O
+failed	O
+to	O
+generate	O
+normally	O
+distributed	O
+data	O
+or	O
+the	O
+equal	O
+variance	O
+test	O
+was	O
+not	O
+satisfied	O
+,	O
+nonparametric	O
+testing	O
+was	O
+performed	O
+using	O
+the	O
+Mann	O
+-	O
+Whitney	O
+rank	O
+sum	O
+test	O
+between	O
+two	O
+groups	O
+and	O
+by	O
+Kruskal	O
+-	O
+Wallis	O
+one	O
+-	O
+way	O
+analysis	O
+of	O
+variance	O
+on	O
+ranks	O
+among	O
+three	O
+or	O
+more	O
+groups	O
+.	O
+
+Correlations	O
+were	O
+determined	O
+using	O
+Pearson	O
+product	O
+moment	O
+correlation	O
+for	O
+interval	O
+data	O
+and	O
+using	O
+Spearman	O
+rank	O
+order	O
+correlation	O
+for	O
+ordinal	O
+data	O
+or	O
+for	O
+interval	O
+data	O
+that	O
+did	O
+not	O
+follow	O
+a	O
+normal	O
+distribution	O
+.	O
+
+Nominal	O
+data	O
+were	O
+analyzed	O
+using	O
+chi	O
+2	O
+analysis	O
+-	O
+of	O
+-	O
+contingency	O
+tables	O
+.	O
+
+Results	O
+
+Elevated	O
+plasma	O
+BLyS	O
+levels	O
+and	O
+blood	O
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+of	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+isoforms	O
+in	O
+systemic	O
+lupus	O
+erythematosus	O
+patients	B
+
+Previous	O
+reports	O
+of	O
+elevated	O
+circulating	O
+BLyS	O
+levels	O
+in	O
+SLE	O
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+on	O
+a	O
+BLyS	O
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+that	O
+utilized	O
+a	O
+whole	O
+(	O
+unfragmented	O
+)	O
+capture	O
+anti	O
+-	O
+BLyS	O
+monoclonal	O
+antibody	O
+[	O
+7	O
+-	O
+9	O
+]	O
+.	O
+
+Since	O
+the	O
+publication	O
+of	O
+these	O
+reports	O
+,	O
+it	O
+has	O
+been	O
+recognized	O
+that	O
+the	O
+presence	O
+of	O
+rheumatoid	O
+factor	O
+can	O
+potentially	O
+interfere	O
+with	O
+the	O
+assay	O
+and	O
+lead	O
+to	O
+spurious	O
+overestimation	O
+of	O
+the	O
+true	O
+circulating	O
+BLyS	O
+levels	O
+(	O
+Human	B
+Genome	O
+Sciences	O
+,	O
+Inc	O
+.	O
+;	O
+unpublished	O
+observations	O
+)	O
+.	O
+
+To	O
+mitigate	O
+potential	O
+interference	O
+from	O
+rheumatoid	O
+factor	O
+,	O
+the	O
+BLyS	O
+ELISA	O
+has	O
+been	O
+modified	O
+and	O
+the	O
+capture	O
+anti	O
+-	O
+BLyS	O
+monoclonal	O
+antibody	O
+is	O
+now	O
+utilized	O
+as	O
+a	O
+Fab	O
+fragment	O
+.	O
+
+Despite	O
+the	O
+changes	O
+in	O
+the	O
+ELISA	O
+format	O
+,	O
+our	O
+findings	O
+are	O
+entirely	O
+consistent	O
+with	O
+those	O
+of	O
+the	O
+previous	O
+reports	O
+.	O
+
+Plasma	O
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+significantly	O
+greater	O
+in	O
+the	O
+SLE	O
+group	O
+than	O
+in	O
+either	O
+RA	O
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+normal	O
+control	O
+group	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+;	O
+Figure	O
+1a	O
+)	O
+.	O
+
+Arbitrary	O
+assignment	O
+of	O
+the	O
+95th	O
+percentile	O
+value	O
+among	O
+the	O
+normal	O
+control	O
+individuals	O
+as	O
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+upper	O
+limit	O
+of	O
+'	O
+normal	O
+'	O
+revealed	O
+that	O
+two	O
+of	O
+the	O
+30	O
+normal	O
+control	O
+individuals	O
+,	O
+15	O
+of	O
+the	O
+60	O
+RA	O
+patients	B
+,	O
+and	O
+29	O
+of	O
+the	O
+60	O
+SLE	O
+patients	B
+harbored	O
+elevated	O
+plasma	O
+BLyS	O
+levels	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Overexpression	O
+of	O
+BLyS	O
+in	O
+SLE	O
+patients	B
+was	O
+also	O
+established	O
+by	O
+measuring	O
+BLyS	O
+mRNA	O
+levels	O
+normalized	O
+to	O
+beta	O
+-	O
+actin	O
+mRNA	O
+levels	O
+in	O
+peripheral	O
+blood	O
+leukocytes	O
+(	O
+buffy	O
+coats	O
+)	O
+.	O
+
+The	O
+geometric	O
+mean	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+among	O
+the	O
+SLE	O
+patients	B
+were	O
+each	O
+significantly	O
+greater	O
+than	O
+those	O
+among	O
+the	O
+RA	O
+patients	B
+and	O
+normal	O
+control	O
+individuals	O
+,	O
+respectively	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+for	O
+each	O
+;	O
+Figure	O
+1b	O
+,	O
+c	O
+)	O
+.	O
+
+Arbitrary	O
+assignment	O
+of	O
+the	O
+95th	O
+percentile	O
+values	O
+for	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+among	O
+the	O
+normal	O
+control	O
+individuals	O
+as	O
+the	O
+upper	O
+limits	O
+of	O
+'	O
+normal	O
+'	O
+revealed	O
+that	O
+two	O
+of	O
+the	O
+30	O
+normal	O
+control	O
+individuals	O
+,	O
+four	O
+of	O
+the	O
+60	O
+RA	O
+patients	B
+,	O
+and	O
+20	O
+of	O
+the	O
+60	O
+SLE	O
+patients	B
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+elevated	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+levels	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
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+two	O
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+the	O
+30	O
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+individuals	O
+,	O
+three	O
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+RA	O
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+,	O
+and	O
+19	O
+of	O
+the	O
+60	O
+SLE	O
+patients	B
+had	O
+elevated	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+(	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+Levels	O
+of	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+strongly	O
+correlated	O
+with	O
+each	O
+other	O
+(	O
+r	O
+=	O
+0	O
+.	O
+703	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+)	O
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+the	O
+SLE	O
+cohort	O
+,	O
+and	O
+plasma	O
+BLyS	O
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+significantly	O
+with	O
+levels	O
+of	O
+each	O
+BLyS	O
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+(	O
+r	O
+=	O
+0	O
+.	O
+429	O
+,	O
+P	O
+<	O
+0	O
+.	O
+001	O
+;	O
+and	O
+r	O
+=	O
+0	O
+.	O
+290	O
+,	O
+P	O
+=	O
+0	O
+.	O
+024	O
+,	O
+respectively	O
+)	O
+.	O
+
+Among	O
+these	O
+SLE	O
+patients	B
+,	O
+none	O
+of	O
+the	O
+measured	O
+BLyS	O
+parameters	O
+correlated	O
+with	O
+patient	B
+age	O
+,	O
+sex	O
+,	O
+race	O
+,	O
+or	O
+daily	O
+dose	O
+of	O
+corticosteroids	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Because	O
+the	O
+racial	O
+composition	O
+of	O
+the	O
+normal	O
+cohort	O
+was	O
+not	O
+as	O
+predominantly	O
+Hispanic	O
+as	O
+were	O
+those	O
+of	O
+the	O
+RA	O
+and	O
+SLE	O
+cohorts	O
+,	O
+we	O
+assessed	O
+the	O
+BLyS	O
+parameters	O
+in	O
+the	O
+respective	O
+Hispanic	O
+subpopulations	O
+.	O
+
+As	O
+for	O
+the	O
+entire	O
+populations	O
+,	O
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+greater	O
+than	O
+those	O
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+either	O
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+normal	O
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+(	O
+P	O
+<	O
+=	O
+0	O
+.	O
+004	O
+;	O
+data	O
+not	O
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+)	O
+.	O
+
+Correlations	O
+between	O
+BLyS	O
+parameters	O
+and	O
+plasma	O
+immunoglobulin	O
+levels	O
+
+BLyS	O
+is	O
+a	O
+potent	O
+B	O
+cell	O
+survival	O
+factor	O
+[	O
+15	O
+-	O
+21	O
+]	O
+,	O
+and	O
+administration	O
+of	O
+exogenous	O
+BLyS	O
+to	O
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+leads	O
+to	O
+B	O
+cell	O
+expansion	O
+and	O
+hypergammaglobulinem	O
+[	O
+1	O
+]	O
+.	O
+
+Previous	O
+studies	O
+with	O
+numbers	O
+of	O
+SLE	O
+patients	B
+greater	O
+than	O
+were	O
+included	O
+in	O
+the	O
+present	O
+study	O
+documented	O
+a	O
+modest	O
+but	O
+significant	O
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+serum	O
+levels	O
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+BLyS	O
+and	O
+IgG	O
+[	O
+8	O
+,	O
+10	O
+]	O
+.	O
+
+In	O
+our	O
+SLE	O
+cohort	O
+of	O
+limited	O
+size	O
+,	O
+plasma	O
+BLyS	O
+levels	O
+failed	O
+to	O
+show	O
+significant	O
+correlations	O
+with	O
+plasma	O
+levels	O
+of	O
+total	O
+immunoglobulin	O
+,	O
+IgG	O
+,	O
+or	O
+IgA	O
+.	O
+
+In	O
+contrast	O
+,	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+correlated	O
+significantly	O
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+each	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+(	O
+None	O
+of	O
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+BLyS	O
+parameters	O
+correlated	O
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+plasma	O
+IgM	O
+levels	O
+.	O
+)	O
+The	O
+absence	O
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+plasma	O
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+the	O
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+when	O
+just	O
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+detectable	O
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+considered	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+133	O
+,	O
+P	O
+=	O
+0	O
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+346	O
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+total	O
+immunoglobulin	O
+;	O
+r	O
+=	O
+-	O
+0	O
+.	O
+048	O
+,	O
+P	O
+=	O
+0	O
+.	O
+734	O
+for	O
+IgG	O
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+r	O
+=	O
+0	O
+.	O
+033	O
+,	O
+P	O
+=	O
+0	O
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+817	O
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+IgA	O
+)	O
+.	O
+
+Correlations	O
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+BLyS	O
+parameters	O
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+disease	O
+activity	O
+
+Previous	O
+studies	O
+either	O
+have	O
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+demonstrate	O
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+significant	O
+correlation	O
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+disease	O
+activity	O
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+BLyS	O
+levels	O
+[	O
+7	O
+-	O
+9	O
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+detected	O
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+a	O
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+correlation	O
+between	O
+the	O
+two	O
+[	O
+10	O
+]	O
+.	O
+
+Consonant	O
+with	O
+those	O
+studies	O
+,	O
+we	O
+identified	O
+no	O
+significant	O
+correlation	O
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+plasma	O
+BLyS	O
+levels	O
+and	O
+SLEDAI	O
+in	O
+our	O
+cohort	O
+of	O
+60	O
+SLE	O
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+(	O
+Figure	O
+3a	O
+)	O
+.	O
+
+The	O
+failure	O
+to	O
+demonstrate	O
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+significant	O
+correlation	O
+cannot	O
+be	O
+attributed	O
+to	O
+a	O
+skewing	O
+of	O
+the	O
+results	O
+by	O
+the	O
+patients	B
+in	O
+whom	O
+plasma	O
+BLyS	O
+levels	O
+were	O
+below	O
+the	O
+limit	O
+of	O
+detection	O
+,	O
+because	O
+no	O
+significant	O
+correlation	O
+was	O
+detected	O
+among	O
+the	O
+53	O
+SLE	O
+patients	B
+in	O
+whom	O
+plasma	O
+BLyS	O
+levels	O
+were	O
+in	O
+the	O
+detectable	O
+range	O
+(	O
+r	O
+=	O
+0	O
+.	O
+185	O
+,	O
+P	O
+=	O
+0	O
+.	O
+183	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+a	O
+significant	O
+correlation	O
+between	O
+SLEDAI	O
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+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+levels	O
+was	O
+readily	O
+discernible	O
+(	O
+Figure	O
+3b	O
+)	O
+.	O
+
+A	O
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+toward	O
+a	O
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+SLEDAI	O
+and	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+was	O
+also	O
+observed	O
+,	O
+although	O
+it	O
+did	O
+not	O
+achieve	O
+statistical	O
+significance	O
+(	O
+Figure	O
+3c	O
+)	O
+.	O
+
+A	O
+component	O
+of	O
+the	O
+SLEDAI	O
+is	O
+the	O
+presence	O
+of	O
+circulating	O
+anti	O
+-	O
+dsDNA	O
+antibodies	O
+.	O
+
+Because	O
+circulating	O
+BLyS	O
+levels	O
+may	O
+affect	O
+the	O
+presence	O
+and	O
+/	O
+or	O
+titers	O
+of	O
+circulating	O
+anti	O
+-	O
+dsDNA	O
+antibodies	O
+[	O
+7	O
+-	O
+10	O
+]	O
+,	O
+we	O
+assessed	O
+correlations	O
+between	O
+the	O
+individual	O
+BLyS	O
+parameters	O
+and	O
+a	O
+modified	O
+SLEDAI	O
+that	O
+excludes	O
+any	O
+consideration	O
+of	O
+anti	O
+-	O
+dsDNA	O
+antibodies	O
+.	O
+
+As	O
+with	O
+the	O
+unmodified	O
+SLEDAI	O
+,	O
+the	O
+modified	O
+SLEDAI	O
+did	O
+not	O
+correlate	O
+with	O
+plasma	O
+BLyS	O
+levels	O
+(	O
+Figure	O
+3d	O
+)	O
+either	O
+among	O
+the	O
+SLE	O
+cohort	O
+overall	O
+or	O
+among	O
+the	O
+53	O
+patients	B
+in	O
+whom	O
+plasma	O
+BLyS	O
+levels	O
+were	O
+in	O
+the	O
+detectable	O
+range	O
+(	O
+r	O
+=	O
+0	O
+.	O
+160	O
+,	O
+P	O
+=	O
+0	O
+.	O
+252	O
+)	O
+,	O
+but	O
+it	O
+significantly	O
+correlated	O
+with	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+levels	O
+(	O
+Figure	O
+3e	O
+)	O
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+exhibited	O
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+BLyS	O
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+levels	O
+(	O
+Figure	O
+3f	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+stronger	O
+correlations	O
+between	O
+BLyS	O
+mRNA	O
+levels	O
+and	O
+disease	O
+activity	O
+cannot	O
+solely	O
+be	O
+explained	O
+by	O
+any	O
+effects	O
+that	O
+BLyS	O
+may	O
+have	O
+on	O
+anti	O
+-	O
+dsDNA	O
+antibodies	O
+per	O
+se	O
+.	O
+
+Moreover	O
+,	O
+among	O
+the	O
+37	O
+SLE	O
+patients	B
+who	O
+were	O
+evaluated	O
+on	O
+two	O
+separate	O
+occasions	O
+,	O
+trends	O
+toward	O
+correlation	O
+were	O
+appreciated	O
+between	O
+changes	O
+in	O
+the	O
+unmodified	O
+or	O
+modified	O
+SLEDAI	O
+and	O
+changes	O
+in	O
+full	O
+-	O
+length	O
+BLyS	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+but	O
+not	O
+changes	O
+in	O
+plasma	O
+BLyS	O
+levels	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+These	O
+results	O
+cannot	O
+be	O
+ascribed	O
+to	O
+changes	O
+in	O
+medications	O
+taken	O
+by	O
+the	O
+patients	B
+,	O
+because	O
+changes	O
+in	O
+neither	O
+disease	O
+activity	O
+nor	O
+in	O
+any	O
+of	O
+the	O
+BLyS	O
+parameters	O
+correlated	O
+with	O
+changes	O
+in	O
+the	O
+doses	O
+of	O
+corticosteroids	O
+or	O
+cytotoxics	O
+taken	O
+by	O
+the	O
+patients	B
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+failure	O
+to	O
+demonstrate	O
+a	O
+meaningful	O
+association	O
+between	O
+changes	O
+in	O
+SLEDAI	O
+score	O
+and	O
+changes	O
+in	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+cannot	O
+be	O
+attributed	O
+to	O
+a	O
+skewing	O
+of	O
+the	O
+results	O
+by	O
+the	O
+patients	B
+in	O
+whom	O
+plasma	O
+BLyS	O
+levels	O
+were	O
+below	O
+the	O
+limit	O
+of	O
+detection	O
+,	O
+because	O
+the	O
+absence	O
+of	O
+association	O
+between	O
+the	O
+two	O
+persisted	O
+among	O
+the	O
+27	O
+SLE	O
+patients	B
+in	O
+whom	O
+plasma	O
+BLyS	O
+levels	O
+were	O
+in	O
+the	O
+detectable	O
+range	O
+in	O
+both	O
+samples	O
+(	O
+r	O
+=	O
+-	O
+0	O
+.	O
+069	O
+,	O
+P	O
+=	O
+0	O
+.	O
+727	O
+for	O
+plasma	O
+BLyS	O
+versus	O
+unmodified	O
+SLEDAI	O
+;	O
+r	O
+=	O
+-	O
+0	O
+.	O
+020	O
+,	O
+P	O
+=	O
+0	O
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+919	O
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+)	O
+.	O
+
+Lack	O
+of	O
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+levels	O
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+isoforms	O
+and	O
+percentages	O
+of	O
+individual	O
+leukocyte	O
+cell	O
+types	O
+
+Among	O
+cells	O
+in	O
+peripheral	O
+blood	O
+,	O
+BLyS	O
+is	O
+predominantly	O
+expressed	O
+by	O
+cells	O
+of	O
+the	O
+myeloid	O
+lineage	O
+(	O
+monocytes	O
+and	O
+neutrophils	O
+)	O
+[	O
+1	O
+,	O
+14	O
+,	O
+22	O
+,	O
+23	O
+]	O
+.	O
+
+Accordingly	O
+,	O
+a	O
+shift	O
+in	O
+the	O
+differential	O
+leukocyte	O
+count	O
+away	O
+from	O
+lymphocytes	O
+to	O
+monocytes	O
+and	O
+/	O
+or	O
+neutrophils	O
+could	O
+substantially	O
+alter	O
+BLyS	O
+mRNA	O
+results	O
+.	O
+
+Because	O
+of	O
+the	O
+limited	O
+amount	O
+of	O
+blood	O
+we	O
+were	O
+permitted	O
+to	O
+obtain	O
+from	O
+the	O
+SLE	O
+patients	B
+(	O
+consequent	O
+to	O
+the	O
+high	O
+prevalence	O
+of	O
+anemia	O
+among	O
+these	O
+patients	B
+)	O
+,	O
+we	O
+were	O
+unable	O
+to	O
+purify	O
+the	O
+individual	O
+leukocyte	O
+populations	O
+for	O
+BLyS	O
+mRNA	O
+analysis	O
+.	O
+
+Nevertheless	O
+,	O
+to	O
+demonstrate	O
+that	O
+the	O
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+mRNA	O
+levels	O
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+SLE	O
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+not	O
+simply	O
+reflect	O
+a	O
+shift	O
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+differential	O
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+count	O
+,	O
+we	O
+assessed	O
+the	O
+correlations	O
+between	O
+the	O
+individual	O
+BLyS	O
+parameters	O
+on	O
+the	O
+one	O
+hand	O
+and	O
+the	O
+percentages	O
+of	O
+blood	O
+neutrophils	O
+,	O
+monocytes	O
+,	O
+and	O
+lymphocytes	O
+on	O
+the	O
+other	O
+.	O
+
+No	O
+correlations	O
+were	O
+appreciated	O
+(	O
+Figure	O
+5	O
+)	O
+.	O
+
+Presence	O
+of	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+in	O
+patients	B
+with	O
+systemic	O
+lupus	O
+erythematosus	O
+
+The	O
+poorer	O
+correlation	O
+between	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+and	O
+disease	O
+activity	O
+compared	O
+with	O
+that	O
+between	O
+BLyS	O
+mRNA	O
+levels	O
+and	O
+disease	O
+activity	O
+was	O
+striking	O
+.	O
+
+Patients	B
+with	O
+SLE	O
+frequently	O
+develop	O
+autoantibodies	O
+against	O
+self	O
+-	O
+antigens	O
+,	O
+and	O
+so	O
+some	O
+of	O
+the	O
+SLE	O
+patients	B
+might	O
+have	O
+harbored	O
+autoantibodies	O
+to	O
+BLyS	O
+.	O
+
+Such	O
+autoantibodies	O
+could	O
+have	O
+complexed	O
+with	O
+BLyS	O
+and	O
+enhanced	O
+its	O
+clearance	O
+,	O
+thereby	O
+masking	O
+BLyS	O
+overproduction	O
+.	O
+
+Alternatively	O
+,	O
+such	O
+autoantibodies	O
+might	O
+have	O
+sterically	O
+blocked	O
+the	O
+epitopes	O
+recognized	O
+by	O
+the	O
+detecting	O
+antibodies	O
+in	O
+the	O
+in	O
+vitro	O
+ELISA	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+measured	O
+BLyS	O
+levels	O
+would	O
+have	O
+been	O
+spuriously	O
+reduced	O
+,	O
+again	O
+masking	O
+BLyS	O
+overproduction	O
+.	O
+
+In	O
+our	O
+cohort	O
+,	O
+IgA	O
+/	O
+IgM	O
+/	O
+IgG	O
+anti	O
+-	O
+BLyS	O
+antibodies	O
+were	O
+detected	O
+in	O
+six	O
+out	O
+of	O
+the	O
+60	O
+SLE	O
+patients	B
+.	O
+
+Such	O
+autoantibodies	O
+were	O
+also	O
+detected	O
+in	O
+two	O
+out	O
+of	O
+60	O
+RA	O
+patients	B
+and	O
+in	O
+one	O
+out	O
+of	O
+30	O
+normal	O
+control	O
+individuals	O
+,	O
+demonstrating	O
+that	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+are	O
+not	O
+restricted	O
+to	O
+SLE	O
+patients	B
+.	O
+
+IgG	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+were	O
+detected	O
+in	O
+3	O
+SLE	O
+patients	B
+but	O
+in	O
+no	O
+RA	O
+patients	B
+or	O
+normal	O
+control	O
+individuals	O
+.	O
+
+Discussion	O
+
+Elevated	O
+blood	O
+levels	O
+of	O
+BLyS	O
+protein	O
+and	O
+mRNA	O
+are	O
+well	O
+described	O
+features	O
+of	O
+human	B
+SLE	O
+[	O
+7	O
+-	O
+9	O
+]	O
+.	O
+
+We	O
+confirmed	O
+these	O
+observations	O
+in	O
+our	O
+study	O
+and	O
+extended	O
+them	O
+by	O
+documenting	O
+increases	O
+not	O
+just	O
+in	O
+levels	O
+of	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+but	O
+also	O
+in	O
+levels	O
+of	O
+Delta	O
+BLyS	O
+mRNA	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Of	O
+note	O
+,	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+elevated	O
+in	O
+SLE	O
+but	O
+not	O
+in	O
+RA	O
+,	O
+raising	O
+the	O
+possibility	O
+that	O
+BLyS	O
+overproduction	O
+in	O
+SLE	O
+is	O
+systemic	O
+whereas	O
+BLyS	O
+overproduction	O
+in	O
+RA	O
+may	O
+be	O
+more	O
+focused	O
+to	O
+the	O
+affected	O
+arthritic	O
+joints	O
+[	O
+24	O
+]	O
+.	O
+
+The	O
+modestly	O
+elevated	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+in	O
+RA	O
+patients	B
+may	O
+reflect	O
+,	O
+at	O
+least	O
+in	O
+part	O
+,	O
+release	O
+of	O
+locally	O
+overproduced	O
+BLyS	O
+into	O
+the	O
+circulation	O
+.	O
+
+The	O
+relationship	O
+between	O
+circulating	O
+BLyS	O
+protein	O
+levels	O
+and	O
+disease	O
+activity	O
+was	O
+addressed	O
+in	O
+several	O
+previous	O
+studies	O
+,	O
+but	O
+significant	O
+correlations	O
+between	O
+the	O
+two	O
+measures	O
+did	O
+not	O
+emerge	O
+[	O
+7	O
+-	O
+9	O
+]	O
+.	O
+
+In	O
+the	O
+largest	O
+study	O
+to	O
+date	O
+,	O
+a	O
+2	O
+-	O
+year	O
+longitudinal	O
+study	O
+of	O
+245	O
+patients	B
+in	O
+which	O
+more	O
+than	O
+1	O
+,	O
+700	O
+plasma	O
+samples	O
+were	O
+analyzed	O
+,	O
+a	O
+significant	O
+but	O
+weak	O
+correlation	O
+between	O
+the	O
+two	O
+was	O
+appreciated	O
+[	O
+10	O
+]	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+a	O
+significant	O
+correlation	O
+between	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+and	O
+disease	O
+activity	O
+was	O
+again	O
+not	O
+realized	O
+(	O
+Figure	O
+3a	O
+,	O
+d	O
+)	O
+.	O
+
+The	O
+weak	O
+,	O
+at	O
+best	O
+,	O
+correlation	O
+between	O
+circulating	O
+BLyS	O
+levels	O
+and	O
+disease	O
+activity	O
+is	O
+seemingly	O
+rather	O
+surprising	O
+.	O
+
+There	O
+is	O
+a	O
+clear	O
+-	O
+cut	O
+association	O
+in	O
+BlyS	O
+transgenic	O
+mice	B
+between	O
+BLyS	O
+overexpression	O
+and	O
+development	O
+of	O
+SLE	O
+-	O
+like	O
+features	O
+[	O
+3	O
+-	O
+5	O
+]	O
+,	O
+and	O
+treatment	O
+of	O
+SLE	O
+-	O
+prone	O
+mice	B
+with	O
+BLyS	O
+antagonists	O
+retards	O
+the	O
+progression	O
+of	O
+disease	O
+and	O
+improves	O
+survival	O
+[	O
+3	O
+,	O
+6	O
+]	O
+.	O
+
+Moreover	O
+,	O
+development	O
+of	O
+precocious	O
+glomerular	O
+pathology	O
+in	O
+autoimmune	O
+-	O
+prone	O
+mice	B
+correlates	O
+strongly	O
+with	O
+circulating	O
+BLyS	O
+levels	O
+[	O
+25	O
+]	O
+.	O
+
+The	O
+likely	O
+explanation	O
+for	O
+the	O
+weak	O
+correlation	O
+between	O
+circulating	O
+BLyS	O
+levels	O
+and	O
+disease	O
+activity	O
+in	O
+human	B
+SLE	O
+is	O
+not	O
+that	O
+disease	O
+activity	O
+in	O
+SLE	O
+patients	B
+is	O
+insensitive	O
+to	O
+the	O
+degree	O
+of	O
+BLyS	O
+overproduction	O
+.	O
+
+Rather	O
+,	O
+a	O
+more	O
+tenable	O
+explanation	O
+is	O
+that	O
+circulating	O
+BLyS	O
+levels	O
+in	O
+human	B
+SLE	O
+do	O
+not	O
+always	O
+accurately	O
+reflect	O
+excessive	O
+endogenous	O
+BLyS	O
+production	O
+.	O
+
+We	O
+can	O
+identify	O
+at	O
+least	O
+three	O
+nonmutually	O
+exclusive	O
+mechanisms	O
+to	O
+explain	O
+a	O
+dissociation	O
+between	O
+the	O
+two	O
+.	O
+
+First	O
+,	O
+SLE	O
+patients	B
+frequently	O
+develop	O
+autoantibodies	O
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+a	O
+myriad	O
+of	O
+self	O
+-	O
+targets	O
+(	O
+for	O
+example	O
+,	O
+erythrocytes	O
+,	O
+lymphocytes	O
+)	O
+.	O
+
+Indeed	O
+,	O
+we	O
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+IgA	O
+/	O
+IgM	O
+/	O
+IgG	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+in	O
+10	O
+%	O
+(	O
+6	O
+/	O
+60	O
+)	O
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+the	O
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+,	O
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+we	O
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+circulating	O
+IgG	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+in	O
+5	O
+%	O
+(	O
+3	O
+/	O
+60	O
+)	O
+.	O
+
+These	O
+percentages	O
+may	O
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+underestimates	O
+of	O
+the	O
+true	O
+prevalence	O
+of	O
+anti	O
+-	O
+BLyS	O
+autoantibodies	O
+,	O
+because	O
+some	O
+of	O
+these	O
+autoantibodies	O
+may	O
+be	O
+saturated	O
+in	O
+vivo	O
+with	O
+circulating	O
+BLyS	O
+,	O
+rendering	O
+them	O
+incapable	O
+of	O
+binding	O
+to	O
+BLyS	O
+in	O
+the	O
+in	O
+vitro	O
+detection	O
+assay	O
+.	O
+
+We	O
+do	O
+not	O
+yet	O
+know	O
+whether	O
+the	O
+anti	O
+-	O
+BLyS	O
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+functionally	O
+neutralizing	O
+but	O
+,	O
+regardless	O
+,	O
+such	O
+autoantibodies	O
+could	O
+enhance	O
+the	O
+clearance	O
+of	O
+BLyS	O
+and	O
+/	O
+or	O
+interfere	O
+with	O
+in	O
+vitro	O
+detection	O
+of	O
+BLyS	O
+,	O
+thereby	O
+masking	O
+endogenous	O
+BLyS	O
+overproduction	O
+.	O
+
+Second	O
+,	O
+increased	O
+urinary	O
+excretion	O
+of	O
+BLyS	O
+has	O
+been	O
+reported	O
+in	O
+SLE	O
+patients	B
+,	O
+especially	O
+among	O
+those	O
+with	O
+clinically	O
+overt	O
+renal	O
+involvement	O
+[	O
+26	O
+]	O
+.	O
+
+At	O
+least	O
+four	O
+of	O
+the	O
+patients	B
+we	O
+studied	O
+manifested	O
+nephrotic	O
+-	O
+range	O
+proteinuria	O
+(	O
+>	O
+=	O
+3	O
+g	O
+/	O
+24	O
+hours	O
+)	O
+,	O
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+so	O
+urinary	O
+loss	O
+of	O
+BLyS	O
+was	O
+probably	O
+substantial	O
+in	O
+at	O
+least	O
+these	O
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+.	O
+
+A	O
+validated	O
+assay	O
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+has	O
+not	O
+yet	O
+been	O
+developed	O
+so	O
+we	O
+were	O
+unable	O
+to	O
+quantify	O
+urinary	O
+BLyS	O
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+.	O
+
+Once	O
+an	O
+assay	O
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+urinary	O
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+is	O
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+,	O
+we	O
+should	O
+be	O
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+to	O
+assess	O
+the	O
+effect	O
+of	O
+urinary	O
+BLyS	O
+excretion	O
+on	O
+circulating	O
+BLyS	O
+levels	O
+.	O
+
+Third	O
+,	O
+BLyS	O
+promotes	O
+in	O
+vivo	O
+expansion	O
+of	O
+B	O
+cells	O
+[	O
+1	O
+]	O
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+
+Freshly	O
+isolated	O
+SLE	O
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+cells	O
+,	O
+despite	O
+intact	O
+surface	O
+expression	O
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+BLyS	O
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+,	O
+bind	O
+less	O
+biotinylated	O
+BLyS	O
+ex	O
+vivo	O
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+do	O
+freshly	O
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+normal	O
+B	O
+cells	O
+[	O
+27	O
+]	O
+.	O
+
+Although	O
+other	O
+interpretations	O
+are	O
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+,	O
+the	O
+most	O
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+is	O
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+BLyS	O
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+B	O
+cells	O
+in	O
+SLE	O
+patients	B
+are	O
+occupied	O
+in	O
+vivo	O
+by	O
+soluble	O
+BLyS	O
+.	O
+
+Accordingly	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+BLyS	O
+receptors	O
+expressed	O
+by	O
+the	O
+expanded	O
+B	O
+cell	O
+population	O
+do	O
+bind	O
+BLyS	O
+and	O
+remove	O
+it	O
+from	O
+the	O
+circulation	O
+,	O
+resulting	O
+in	O
+a	O
+homeostatic	O
+pathway	O
+that	O
+modulates	O
+the	O
+effects	O
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+BLyS	O
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+on	O
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+BLyS	O
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+.	O
+
+Indeed	O
+,	O
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+levels	O
+of	O
+BLyS	O
+rise	O
+with	O
+peripheral	O
+blood	O
+B	O
+cell	O
+depletion	O
+and	O
+fall	O
+with	O
+re	O
+-	O
+emergence	O
+of	O
+peripheral	O
+blood	O
+B	O
+cells	O
+in	O
+rituximab	O
+-	O
+treated	O
+RA	O
+or	O
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+patients	B
+[	O
+28	O
+,	O
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+]	O
+,	O
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+this	O
+inverse	O
+relationship	O
+between	O
+circulating	O
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+levels	O
+and	O
+B	O
+cell	O
+load	O
+.	O
+
+Moreover	O
+,	O
+one	O
+of	O
+the	O
+hallmarks	O
+of	O
+active	O
+disease	O
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+the	O
+increased	O
+percentages	O
+of	O
+activated	O
+B	O
+cells	O
+and	O
+plasma	O
+cells	O
+in	O
+peripheral	O
+blood	O
+[	O
+30	O
+-	O
+34	O
+]	O
+,	O
+probably	O
+reflecting	O
+increased	O
+systemic	O
+numbers	O
+of	O
+activated	O
+B	O
+cells	O
+and	O
+plasma	O
+cells	O
+.	O
+
+Although	O
+not	O
+yet	O
+formally	O
+tested	O
+,	O
+differential	O
+BLyS	O
+receptor	O
+expression	O
+by	O
+these	O
+cells	O
+compared	O
+with	O
+expression	O
+by	O
+nonactivated	O
+B	O
+cells	O
+may	O
+result	O
+in	O
+increased	O
+peripheral	O
+BLyS	O
+utilization	O
+,	O
+further	O
+dampening	O
+the	O
+effects	O
+of	O
+BLyS	O
+overproduction	O
+on	O
+circulating	O
+protein	O
+levels	O
+.	O
+
+To	O
+circumvent	O
+these	O
+confounding	O
+processes	O
+,	O
+we	O
+used	O
+BLyS	O
+mRNA	O
+levels	O
+as	O
+a	O
+surrogate	O
+marker	O
+of	O
+endogenous	O
+BLyS	O
+production	O
+.	O
+
+Overall	O
+,	O
+the	O
+correlations	O
+between	O
+disease	O
+activity	O
+and	O
+either	O
+full	O
+-	O
+length	O
+BLyS	O
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+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+much	O
+stronger	O
+than	O
+that	O
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+disease	O
+activity	O
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+BLyS	O
+protein	O
+levels	O
+(	O
+Figures	O
+3	O
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+4	O
+)	O
+.	O
+
+This	O
+was	O
+the	O
+case	O
+regardless	O
+of	O
+whether	O
+we	O
+used	O
+the	O
+standard	O
+SLEDAI	O
+or	O
+the	O
+modified	O
+SLEDAI	O
+as	O
+a	O
+measure	O
+of	O
+disease	O
+activity	O
+.	O
+
+These	O
+correlations	O
+were	O
+not	O
+spurious	O
+ones	O
+consequent	O
+to	O
+shifts	O
+in	O
+percentages	O
+of	O
+leukocyte	O
+subpopulations	O
+in	O
+peripheral	O
+blood	O
+,	O
+because	O
+BLyS	O
+mRNA	O
+levels	O
+did	O
+not	O
+correlate	O
+with	O
+percentages	O
+of	O
+blood	O
+neutrophils	O
+,	O
+monocytes	O
+,	O
+or	O
+lymphocytes	O
+(	O
+Figure	O
+5	O
+)	O
+.	O
+
+A	O
+similar	O
+pattern	O
+was	O
+observed	O
+between	O
+plasma	O
+immunoglobulin	O
+levels	O
+and	O
+the	O
+BLyS	O
+parameters	O
+,	O
+with	O
+plasma	O
+levels	O
+of	O
+total	O
+immunoglobulin	O
+,	O
+IgG	O
+,	O
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+with	O
+full	O
+-	O
+length	O
+BLyS	O
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+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+but	O
+not	O
+with	O
+plasma	O
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+levels	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+These	O
+significant	O
+correlations	O
+between	O
+full	O
+-	O
+length	O
+BLyS	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+and	O
+plasma	O
+immunoglobulin	O
+levels	O
+again	O
+highlight	O
+the	O
+greater	O
+ability	O
+of	O
+BLyS	O
+mRNA	O
+levels	O
+,	O
+compared	O
+with	O
+plasma	O
+BLyS	O
+protein	O
+levels	O
+,	O
+to	O
+reflect	O
+ongoing	O
+BLyS	O
+overproduction	O
+.	O
+
+At	O
+present	O
+,	O
+it	O
+is	O
+not	O
+known	O
+whether	O
+soluble	O
+Delta	O
+BLyS	O
+protein	O
+is	O
+present	O
+in	O
+the	O
+circulation	O
+of	O
+SLE	O
+patients	B
+or	O
+of	O
+normal	O
+individuals	O
+.	O
+
+Although	O
+full	O
+-	O
+length	O
+BLyS	O
+protein	O
+is	O
+readily	O
+cleaved	O
+and	O
+released	O
+from	O
+cells	O
+transfected	O
+with	O
+a	O
+vector	O
+containing	O
+murine	B
+full	O
+-	O
+length	O
+BLyS	O
+,	O
+Delta	O
+BLyS	O
+protein	O
+is	O
+not	O
+cleaved	O
+or	O
+released	O
+from	O
+murine	B
+Delta	O
+BLyS	O
+transfectants	O
+[	O
+11	O
+]	O
+.	O
+
+Given	O
+the	O
+strong	O
+similarities	O
+between	O
+murine	B
+and	O
+human	B
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+Delta	O
+BLyS	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+human	B
+soluble	O
+Delta	O
+BLyS	O
+protein	O
+is	O
+also	O
+not	O
+cleaved	O
+from	O
+the	O
+cell	O
+surface	O
+and	O
+released	O
+into	O
+the	O
+circulation	O
+.	O
+
+Moreover	O
+,	O
+soluble	O
+Delta	O
+BLyS	O
+protein	O
+is	O
+not	O
+released	O
+from	O
+cells	O
+transfected	O
+with	O
+a	O
+vector	O
+containing	O
+just	O
+the	O
+extracellular	O
+domain	O
+of	O
+human	B
+Delta	O
+BLyS	O
+(	O
+which	O
+encodes	O
+the	O
+soluble	O
+protein	O
+;	O
+A	O
+.	O
+L	O
+.	O
+Gavin	O
+,	O
+unpublished	O
+observations	O
+)	O
+.	O
+
+Whether	O
+this	O
+reflects	O
+rapid	O
+intracellular	O
+degradation	O
+of	O
+soluble	O
+Delta	O
+BLyS	O
+or	O
+some	O
+other	O
+impediment	O
+to	O
+its	O
+release	O
+remains	O
+unknown	O
+.	O
+
+Regardless	O
+,	O
+if	O
+the	O
+inability	O
+to	O
+release	O
+soluble	O
+Delta	O
+BLyS	O
+in	O
+vitro	O
+faithfully	O
+recapitulates	O
+in	O
+vivo	O
+biology	O
+,	O
+then	O
+the	O
+stronger	O
+associations	O
+between	O
+SLE	O
+disease	O
+activity	O
+and	O
+full	O
+-	O
+length	O
+BLyS	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+compared	O
+with	O
+that	O
+between	O
+SLE	O
+disease	O
+activity	O
+and	O
+BLyS	O
+protein	O
+levels	O
+could	O
+not	O
+be	O
+attributable	O
+to	O
+interference	O
+by	O
+biologically	O
+inactive	O
+(	O
+inhibitory	O
+)	O
+Delta	O
+BLyS	O
+protein	O
+in	O
+the	O
+BLyS	O
+protein	O
+detection	O
+ELISA	O
+.	O
+
+Importantly	O
+,	O
+even	O
+if	O
+soluble	O
+Delta	O
+BLyS	O
+protein	O
+is	O
+present	O
+in	O
+the	O
+circulation	O
+and	O
+is	O
+detected	O
+by	O
+the	O
+BLyS	O
+protein	O
+detection	O
+ELISA	O
+,	O
+then	O
+the	O
+stronger	O
+correlations	O
+between	O
+SLE	O
+disease	O
+activity	O
+and	O
+full	O
+-	O
+length	O
+BLyS	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+than	O
+that	O
+between	O
+disease	O
+activity	O
+and	O
+total	O
+BLyS	O
+(	O
+including	O
+Delta	O
+BLyS	O
+)	O
+protein	O
+levels	O
+suggest	O
+that	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+/	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+may	O
+operationally	O
+serve	O
+as	O
+useful	O
+biomarkers	O
+of	O
+disease	O
+activity	O
+in	O
+SLE	O
+.	O
+
+Although	O
+the	O
+complexity	O
+and	O
+labor	O
+intensiveness	O
+associated	O
+with	O
+quantitative	O
+real	O
+-	O
+time	O
+PCR	O
+may	O
+render	O
+measurement	O
+of	O
+BLyS	O
+mRNA	O
+levels	O
+impracticable	O
+for	O
+routine	O
+clinical	O
+practice	O
+,	O
+such	O
+measurement	O
+could	O
+readily	O
+be	O
+incorporated	O
+into	O
+clinical	O
+trials	O
+and	O
+yield	O
+valuable	O
+information	O
+.	O
+
+Longitudinal	O
+observations	O
+in	O
+large	O
+numbers	O
+of	O
+SLE	O
+patients	B
+will	O
+be	O
+necessary	O
+to	O
+establish	O
+or	O
+refute	O
+the	O
+utility	O
+of	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+/	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+to	O
+subserve	O
+this	O
+clinically	O
+vital	O
+function	O
+.	O
+
+Although	O
+expression	O
+of	O
+the	O
+two	O
+major	O
+BLyS	O
+isoforms	O
+was	O
+highly	O
+coordinate	O
+among	O
+SLE	O
+patients	B
+,	O
+there	O
+were	O
+several	O
+patients	B
+in	O
+whom	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+markedly	O
+greater	O
+than	O
+or	O
+less	O
+than	O
+the	O
+expected	O
+values	O
+based	O
+on	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+levels	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+This	O
+raises	O
+the	O
+possibility	O
+that	O
+dysregulation	O
+of	O
+Delta	O
+BLyS	O
+may	O
+contribute	O
+to	O
+overall	O
+BLyS	O
+dysregulation	O
+in	O
+at	O
+least	O
+some	O
+SLE	O
+patients	B
+.	O
+
+It	O
+is	O
+known	O
+that	O
+interferon	O
+-	O
+gamma	O
+,	O
+interleukin	O
+-	O
+10	O
+,	O
+interferon	O
+-	O
+alpha	O
+,	O
+and	O
+CD154	O
+can	O
+upregulate	O
+full	O
+-	O
+length	O
+BLyS	O
+mRNA	O
+levels	O
+[	O
+14	O
+,	O
+22	O
+,	O
+35	O
+]	O
+,	O
+but	O
+it	O
+is	O
+not	O
+known	O
+what	O
+effects	O
+these	O
+or	O
+other	O
+cytokines	O
+/	O
+cell	O
+-	O
+surface	O
+structures	O
+have	O
+on	O
+Delta	O
+BLyS	O
+expression	O
+.	O
+
+Further	O
+investigation	O
+of	O
+the	O
+regulation	O
+of	O
+Delta	O
+BLyS	O
+and	O
+the	O
+differential	O
+expression	O
+of	O
+BLyS	O
+isoforms	O
+is	O
+certainly	O
+warranted	O
+.	O
+
+Although	O
+the	O
+associations	O
+between	O
+full	O
+-	O
+length	O
+BLyS	O
+and	O
+/	O
+or	O
+Delta	O
+BLyS	O
+mRNA	O
+levels	O
+and	O
+disease	O
+activity	O
+in	O
+SLE	O
+were	O
+usually	O
+strong	O
+when	O
+the	O
+SLE	O
+cohort	O
+was	O
+analyzed	O
+in	O
+aggregate	O
+,	O
+there	O
+were	O
+several	O
+SLE	O
+patients	B
+in	O
+whom	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+quite	O
+high	O
+despite	O
+little	O
+objective	O
+ongoing	O
+disease	O
+activity	O
+,	O
+and	O
+there	O
+were	O
+several	O
+SLE	O
+patients	B
+in	O
+whom	O
+BLyS	O
+mRNA	O
+levels	O
+were	O
+low	O
+despite	O
+considerable	O
+ongoing	O
+disease	O
+activity	O
+.	O
+
+One	O
+must	O
+recognize	O
+that	O
+the	O
+bulk	O
+of	O
+the	O
+pathogenic	O
+autoimmune	O
+responses	O
+probably	O
+takes	O
+place	O
+in	O
+the	O
+spleen	O
+and	O
+lymph	O
+nodes	O
+,	O
+rather	O
+than	O
+in	O
+the	O
+peripheral	O
+blood	O
+,	O
+where	O
+myeloid	O
+lineage	O
+cells	O
+(	O
+for	O
+example	O
+,	O
+dendritic	O
+cells	O
+)	O
+produce	O
+BLyS	O
+and	O
+support	O
+B	O
+cell	O
+survival	O
+and	O
+expansion	O
+[	O
+36	O
+]	O
+.	O
+
+Local	O
+BLyS	O
+production	O
+in	O
+the	O
+secondary	O
+lymphoid	O
+tissues	O
+will	O
+be	O
+more	O
+important	O
+to	O
+the	O
+development	O
+and	O
+maintenance	O
+of	O
+an	O
+autoimmune	O
+response	O
+than	O
+will	O
+remote	O
+BLyS	O
+levels	O
+in	O
+the	O
+circulation	O
+.	O
+
+Because	O
+at	O
+least	O
+some	O
+autoreactive	O
+B	O
+cells	O
+may	O
+be	O
+more	O
+sensitive	O
+to	O
+BLyS	O
+-	O
+mediated	O
+survival	O
+signals	O
+than	O
+non	O
+-	O
+autoreactive	O
+B	O
+cells	O
+[	O
+37	O
+,	O
+38	O
+]	O
+,	O
+local	O
+increases	O
+in	O
+BLyS	O
+production	O
+could	O
+preferentially	O
+promote	O
+expansion	O
+of	O
+autoreactive	O
+B	O
+cells	O
+.	O
+
+These	O
+cells	O
+,	O
+in	O
+turn	O
+,	O
+could	O
+activate	O
+autoreactive	O
+T	O
+cells	O
+by	O
+presenting	O
+autoantigen	O
+to	O
+them	O
+,	O
+and	O
+some	O
+of	O
+the	O
+autoreactive	O
+B	O
+cells	O
+would	O
+respond	O
+to	O
+T	O
+cell	O
+derived	O
+signals	O
+and	O
+mature	O
+into	O
+(	O
+pathogenic	O
+)	O
+autoantibody	O
+secreting	O
+plasma	O
+cells	O
+.	O
+
+In	O
+contrast	O
+to	O
+murine	B
+studies	O
+,	O
+in	O
+which	O
+investigators	O
+can	O
+readily	O
+harvest	O
+and	O
+analyze	O
+lymphoid	O
+and	O
+myeloid	O
+lineage	O
+cells	O
+from	O
+any	O
+site	O
+(	O
+for	O
+example	O
+,	O
+spleen	O
+,	O
+bone	O
+marrow	O
+)	O
+,	O
+such	O
+is	O
+not	O
+the	O
+case	O
+for	O
+human	B
+studies	O
+.	O
+
+Peripheral	O
+blood	O
+is	O
+the	O
+only	O
+site	O
+readily	O
+accessible	O
+for	O
+human	B
+studies	O
+,	O
+and	O
+it	O
+is	O
+possible	O
+that	O
+,	O
+at	O
+least	O
+in	O
+some	O
+patients	B
+,	O
+BLyS	O
+mRNA	O
+levels	O
+in	O
+circulating	O
+leukocytes	O
+do	O
+not	O
+reflect	O
+local	O
+BLyS	O
+production	O
+in	O
+the	O
+secondary	O
+lymphoid	O
+tissues	O
+.	O
+
+One	O
+must	O
+also	O
+recognize	O
+that	O
+disease	O
+activity	O
+in	O
+SLE	O
+is	O
+not	O
+solely	O
+driven	O
+by	O
+B	O
+cells	O
+.	O
+
+Systemic	O
+inflammation	O
+and	O
+SLE	O
+flares	O
+can	O
+be	O
+triggered	O
+via	O
+B	O
+cell	O
+independent	O
+means	O
+.	O
+
+Not	O
+all	O
+SLE	O
+patients	B
+treated	O
+with	O
+a	O
+B	O
+cell	O
+depleting	O
+course	O
+of	O
+rituximab	O
+experience	O
+clinical	O
+remission	O
+[	O
+39	O
+]	O
+,	O
+strongly	O
+pointing	O
+to	O
+the	O
+importance	O
+of	O
+non	O
+-	O
+B	O
+cells	O
+in	O
+disease	O
+pathogenesis	O
+/	O
+maintenance	O
+.	O
+
+Conversely	O
+,	O
+not	O
+all	O
+pathogenic	O
+B	O
+cells	O
+necessarily	O
+require	O
+high	O
+levels	O
+of	O
+BLyS	O
+to	O
+effect	O
+their	O
+pathogenicity	O
+.	O
+
+Murine	O
+studies	O
+have	O
+unequivocally	O
+documented	O
+B	O
+cell	O
+subpopulations	O
+that	O
+do	O
+not	O
+depend	O
+upon	O
+BLyS	O
+for	O
+their	O
+survival	O
+[	O
+40	O
+-	O
+42	O
+]	O
+.	O
+
+Although	O
+mice	B
+completely	O
+devoid	O
+of	O
+BLyS	O
+have	O
+reduced	O
+numbers	O
+of	O
+mature	O
+B	O
+cells	O
+and	O
+harbor	O
+reduced	O
+levels	O
+of	O
+immunoglobulin	O
+,	O
+these	O
+reductions	O
+are	O
+incomplete	O
+.	O
+
+Thus	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+some	O
+SLE	O
+patients	B
+harbor	O
+pathogenic	O
+B	O
+cells	O
+that	O
+are	O
+relatively	O
+insensitive	O
+to	O
+BLyS	O
+and	O
+could	O
+drive	O
+considerable	O
+disease	O
+activity	O
+even	O
+in	O
+the	O
+context	O
+of	O
+low	O
+endogenous	O
+BLyS	O
+production	O
+.	O
+
+Conversely	O
+,	O
+patients	B
+with	O
+high	O
+BLyS	O
+mRNA	O
+levels	O
+may	O
+be	O
+those	O
+patients	B
+whose	O
+disease	O
+is	O
+strongly	O
+driven	O
+by	O
+BLyS	O
+and	O
+may	O
+be	O
+especially	O
+helped	O
+by	O
+BLyS	O
+antagonist	O
+therapy	O
+.	O
+
+Future	O
+clinical	O
+trials	O
+should	O
+be	O
+able	O
+to	O
+establish	O
+whether	O
+the	O
+BLyS	O
+mRNA	O
+levels	O
+are	O
+good	O
+predictors	O
+of	O
+response	O
+to	O
+such	O
+agents	O
+.	O
+
+Conclusion	O
+
+Plasma	O
+total	O
+immunoglobulin	O
+,	O
+IgG	O
+,	O
+and	O
+IgA	O
+levels	O
+and	O
+disease	O
+activity	O
+(	O
+as	O
+measured	O
+by	O
+SLEDAI	O
+)	O
+in	O
+SLE	O
+patients	B
+correlate	O
+more	O
+closely	O
+with	O
+peripheral	O
+blood	O
+leukocyte	O
+levels	O
+of	O
+BLyS	O
+mRNA	O
+than	O
+with	O
+plasma	O
+levels	O
+of	O
+BLyS	O
+protein	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+BLyS	O
+mRNA	O
+levels	O
+better	O
+reflect	O
+in	O
+vivo	O
+BLyS	O
+production	O
+than	O
+do	O
+circulating	O
+BLyS	O
+protein	O
+levels	O
+,	O
+and	O
+may	O
+be	O
+a	O
+useful	O
+biomarker	O
+in	O
+the	O
+clinical	O
+monitoring	O
+of	O
+SLE	O
+patients	B
+.	O
+
+These	O
+findings	O
+also	O
+support	O
+the	O
+premise	O
+that	O
+BLyS	O
+overexpression	O
+not	O
+only	O
+promotes	O
+development	O
+of	O
+disease	O
+but	O
+also	O
+actively	O
+contributes	O
+to	O
+the	O
+ongoing	O
+maintenance	O
+of	O
+disease	O
+in	O
+SLE	O
+patients	B
+.	O
+
+This	O
+reinforces	O
+the	O
+rationale	O
+underlying	O
+clinical	O
+trials	O
+with	O
+BLyS	O
+antagonists	O
+in	O
+SLE	O
+.	O
+
+Abbreviations	O
+
+anti	O
+-	O
+dsDNA	O
+=	O
+anti	O
+-	O
+double	O
+-	O
+stranded	O
+DNA	O
+;	O
+BLyS	O
+=	O
+B	O
+lymphocyte	O
+stimulator	O
+;	O
+bp	O
+=	O
+base	O
+pairs	O
+;	O
+Ct	O
+=	O
+threshold	O
+cycle	O
+;	O
+ELISA	O
+=	O
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+;	O
+PCR	O
+=	O
+polymerase	O
+chain	O
+reaction	O
+;	O
+RA	O
+=	O
+rheumatoid	O
+arthritis	O
+;	O
+SLE	O
+=	O
+systemic	O
+lupus	O
+erythematosus	O
+;	O
+SLEDAI	O
+=	O
+SLE	O
+Disease	O
+Activity	O
+Index	O
+.	O
+
+Competing	O
+interests	O
+
+TSM	O
+and	O
+DMH	O
+were	O
+employees	O
+of	O
+Human	B
+Genome	O
+Sciences	O
+(	O
+HGS	O
+)	O
+at	O
+the	O
+time	O
+the	O
+investigation	O
+was	O
+conducted	O
+.	O
+
+(	O
+DMH	O
+has	O
+since	O
+left	O
+the	O
+company	O
+.	O
+)	O
+WS	O
+has	O
+received	O
+research	O
+support	O
+from	O
+HGS	O
+and	O
+has	O
+served	O
+as	O
+a	O
+consultant	O
+to	O
+HGS	O
+(	O
+<	O
+$	O
+10	O
+,	O
+000	O
+)	O
+.	O
+
+CEC	O
+,	O
+ALG	O
+,	O
+and	O
+DN	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+CEC	O
+identified	O
+and	O
+recruited	O
+all	O
+participants	B
+;	O
+collected	O
+all	O
+the	O
+blood	O
+samples	O
+and	O
+reviewed	O
+all	O
+the	O
+medical	O
+charts	O
+;	O
+and	O
+wrote	O
+the	O
+initial	O
+working	O
+draft	O
+of	O
+this	O
+manuscript	O
+.	O
+
+ALG	O
+developed	O
+and	O
+performed	O
+all	O
+the	O
+real	O
+-	O
+time	O
+PCR	O
+assays	O
+and	O
+assisted	O
+in	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+and	O
+in	O
+writing	O
+the	O
+final	O
+version	O
+of	O
+the	O
+manuscript	O
+.	O
+
+TSM	O
+performed	O
+the	O
+plasma	O
+BLyS	O
+protein	O
+and	O
+anti	O
+-	O
+BLyS	O
+assays	O
+and	O
+assisted	O
+in	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+and	O
+in	O
+writing	O
+the	O
+final	O
+version	O
+of	O
+the	O
+manuscript	O
+.	O
+
+DMH	O
+assisted	O
+in	O
+the	O
+design	O
+in	O
+the	O
+study	O
+,	O
+in	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+,	O
+and	O
+in	O
+writing	O
+the	O
+final	O
+version	O
+of	O
+the	O
+manuscript	O
+.	O
+
+DN	O
+assisted	O
+in	O
+the	O
+design	O
+in	O
+the	O
+study	O
+,	O
+in	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+,	O
+and	O
+in	O
+writing	O
+the	O
+final	O
+version	O
+of	O
+the	O
+manuscript	O
+.	O
+
+WS	O
+conceived	O
+the	O
+study	O
+,	O
+supervised	O
+the	O
+recruitment	O
+of	O
+participants	B
+,	O
+performed	O
+the	O
+statistical	O
+analyses	O
+,	O
+assisted	O
+in	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+,	O
+and	O
+supervised	O
+the	O
+editing	O
+of	O
+the	O
+manuscript	O
+to	O
+its	O
+final	O
+form	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+version	O
+.	O
+
+Travel	O
+-	O
+Related	O
+Venous	O
+Thrombosis	O
+:	O
+Results	O
+from	O
+a	O
+Large	O
+Population	O
+-	O
+Based	O
+Case	O
+Control	O
+Study	O
+(	O
+MEGA	O
+Study	O
+)	O
+
+Abstract	O
+
+Background	O
+
+Recent	O
+studies	O
+have	O
+indicated	O
+an	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+after	O
+air	O
+travel	O
+.	O
+
+Nevertheless	O
+,	O
+questions	O
+on	O
+the	O
+magnitude	O
+of	O
+risk	O
+,	O
+the	O
+underlying	O
+mechanism	O
+,	O
+and	O
+modifying	O
+factors	O
+remain	O
+unanswered	O
+.	O
+
+Methods	O
+and	O
+Findings	O
+
+We	O
+studied	O
+the	O
+effect	O
+of	O
+various	O
+modes	O
+and	O
+duration	O
+of	O
+travel	O
+on	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+in	O
+a	O
+large	O
+ongoing	O
+case	O
+-	O
+control	O
+study	O
+on	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+in	O
+an	O
+unselected	O
+population	O
+(	O
+MEGA	O
+study	O
+)	O
+.	O
+
+We	O
+also	O
+assessed	O
+the	O
+combined	O
+effect	O
+of	O
+travel	O
+and	O
+prothrombotic	O
+mutations	O
+,	O
+body	O
+mass	O
+index	O
+,	O
+height	O
+,	O
+and	O
+oral	O
+contraceptive	O
+use	O
+.	O
+
+Since	O
+March	O
+1999	O
+,	O
+consecutive	O
+patients	B
+younger	O
+than	O
+70	O
+y	O
+with	O
+a	O
+first	O
+venous	O
+thrombosis	O
+have	O
+been	O
+invited	O
+to	O
+participate	O
+in	O
+the	O
+study	O
+,	O
+with	O
+their	O
+partners	O
+serving	O
+as	O
+matched	O
+control	O
+individuals	O
+.	O
+
+Information	O
+has	O
+been	O
+collected	O
+on	O
+acquired	O
+and	O
+genetic	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+.	O
+
+Of	O
+1	O
+,	O
+906	O
+patients	B
+,	O
+233	O
+had	O
+traveled	O
+for	O
+more	O
+than	O
+4	O
+h	O
+in	O
+the	O
+8	O
+wk	O
+preceding	O
+the	O
+event	O
+.	O
+
+Traveling	O
+in	O
+general	O
+was	O
+found	O
+to	O
+increase	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+2	O
+-	O
+fold	O
+(	O
+odds	O
+ratio	O
+[	O
+OR	O
+]	O
+2	O
+.	O
+1	O
+;	O
+95	O
+%	O
+confidence	O
+interval	O
+[	O
+CI	O
+]	O
+1	O
+.	O
+5	O
+-	O
+3	O
+.	O
+0	O
+)	O
+.	O
+
+The	O
+risk	O
+of	O
+flying	O
+was	O
+similar	O
+to	O
+the	O
+risks	O
+of	O
+traveling	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+.	O
+
+The	O
+risk	O
+was	O
+highest	O
+in	O
+the	O
+first	O
+week	O
+after	O
+traveling	O
+.	O
+
+Travel	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+led	O
+to	O
+a	O
+high	O
+relative	O
+risk	O
+of	O
+thrombosis	O
+in	O
+individuals	O
+with	O
+factor	O
+V	O
+Leiden	O
+(	O
+OR	O
+8	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+2	O
+.	O
+7	O
+-	O
+24	O
+.	O
+7	O
+)	O
+,	O
+in	O
+those	O
+who	O
+had	O
+a	O
+body	O
+mass	O
+index	O
+of	O
+more	O
+than	O
+30	O
+kg	O
+/	O
+m2	O
+(	O
+OR	O
+9	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+3	O
+.	O
+6	O
+-	O
+27	O
+.	O
+6	O
+)	O
+,	O
+in	O
+those	O
+who	O
+were	O
+more	O
+than	O
+1	O
+.	O
+90	O
+m	O
+tall	O
+(	O
+OR	O
+4	O
+.	O
+7	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+4	O
+-	O
+15	O
+.	O
+4	O
+)	O
+,	O
+and	O
+in	O
+those	O
+who	O
+used	O
+oral	O
+contraceptives	O
+(	O
+estimated	O
+OR	O
+>	O
+20	O
+)	O
+.	O
+
+For	O
+air	O
+travel	O
+these	O
+synergistic	O
+findings	O
+were	O
+more	O
+apparent	O
+,	O
+while	O
+people	B
+shorter	O
+than	O
+1	O
+.	O
+60	O
+m	O
+had	O
+an	O
+increased	O
+risk	O
+of	O
+thrombosis	O
+after	O
+air	O
+travel	O
+(	O
+OR	O
+4	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+9	O
+-	O
+25	O
+.	O
+6	O
+)	O
+as	O
+well	O
+.	O
+
+Conclusions	O
+
+The	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+after	O
+travel	O
+is	O
+moderately	O
+increased	O
+for	O
+all	O
+modes	O
+of	O
+travel	O
+.	O
+
+Subgroups	O
+exist	O
+in	O
+which	O
+the	O
+risk	O
+is	O
+highly	O
+increased	O
+.	O
+
+Background	O
+.	O
+
+Recently	O
+there	O
+has	O
+been	O
+increasing	O
+concern	O
+that	O
+blood	O
+clots	O
+(	O
+thromboses	O
+)	O
+in	O
+the	O
+leg	O
+or	O
+lungs	O
+occur	O
+with	O
+greater	O
+frequency	O
+after	O
+air	O
+travel	O
+.	O
+
+Several	O
+theories	O
+have	O
+been	O
+put	O
+forward	O
+to	O
+explain	O
+why	O
+this	O
+increase	O
+might	O
+happen	O
+,	O
+including	O
+the	O
+fact	O
+that	O
+air	O
+passengers	O
+tend	O
+to	O
+not	O
+move	O
+around	O
+much	O
+,	O
+or	O
+possibly	O
+that	O
+reduced	O
+amounts	O
+of	O
+oxygen	O
+in	O
+the	O
+blood	O
+make	O
+the	O
+blood	O
+more	O
+likely	O
+to	O
+clot	O
+.	O
+
+Understanding	O
+what	O
+causes	O
+such	O
+clots	O
+is	O
+important	O
+as	O
+it	O
+would	O
+help	O
+us	O
+come	O
+up	O
+with	O
+suggestions	O
+of	O
+ways	O
+to	O
+prevent	O
+them	O
+.	O
+
+Why	O
+Was	O
+This	O
+Study	O
+Done	O
+?	O
+
+It	O
+is	O
+not	O
+possible	O
+to	O
+test	O
+in	O
+a	O
+controlled	O
+trial	O
+whether	O
+travel	O
+causes	O
+an	O
+increase	O
+in	O
+blood	O
+clots	O
+,	O
+so	O
+the	O
+next	O
+best	O
+way	O
+of	O
+studying	O
+this	O
+problem	O
+is	O
+to	O
+do	O
+a	O
+case	O
+-	O
+control	O
+study	O
+,	O
+in	O
+which	O
+people	B
+with	O
+blood	O
+clots	O
+(	O
+cases	O
+)	O
+are	O
+compared	O
+with	O
+similar	O
+people	B
+who	O
+don	O
+'	O
+t	O
+have	O
+a	O
+blood	O
+clot	O
+(	O
+controls	O
+-	O
+-	O
+in	O
+this	O
+case	O
+,	O
+the	O
+partners	O
+of	O
+the	O
+cases	O
+)	O
+,	O
+and	O
+the	O
+differences	O
+in	O
+a	O
+number	O
+of	O
+contributing	O
+factors	O
+are	O
+assessed	O
+.	O
+
+What	O
+Did	O
+the	O
+Researchers	O
+Do	O
+and	O
+Find	O
+?	O
+
+Since	O
+1999	O
+,	O
+the	O
+MEGA	O
+(	O
+Multiple	O
+Environmental	O
+and	O
+Genetic	O
+Assessment	O
+of	O
+Risk	O
+Factors	O
+for	O
+Venous	O
+Thrombosis	O
+)	O
+study	O
+has	O
+aimed	O
+to	O
+identify	O
+all	O
+people	B
+in	O
+an	O
+area	O
+of	O
+the	O
+Netherlands	O
+who	O
+develop	O
+a	O
+blood	O
+clot	O
+for	O
+the	O
+first	O
+time	O
+,	O
+by	O
+seeking	O
+out	O
+people	B
+who	O
+receive	O
+treatment	O
+for	O
+blood	O
+clots	O
+.	O
+
+At	O
+the	O
+time	O
+of	O
+this	O
+report	O
+,	O
+1	O
+,	O
+906	O
+people	B
+with	O
+clots	O
+had	O
+been	O
+found	O
+;	O
+of	O
+these	O
+,	O
+233	O
+had	O
+traveled	O
+for	O
+more	O
+than	O
+four	O
+hours	O
+in	O
+the	O
+eight	O
+weeks	O
+preceding	O
+the	O
+event	O
+.	O
+
+Traveling	O
+in	O
+general	O
+was	O
+found	O
+to	O
+increase	O
+the	O
+risk	O
+of	O
+clots	O
+two	O
+-	O
+fold	O
+,	O
+and	O
+the	O
+risk	O
+was	O
+highest	O
+in	O
+the	O
+week	O
+after	O
+traveling	O
+.	O
+
+The	O
+risk	O
+of	O
+flying	O
+was	O
+similar	O
+to	O
+the	O
+risk	O
+of	O
+traveling	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+,	O
+and	O
+was	O
+highest	O
+in	O
+the	O
+first	O
+week	O
+after	O
+traveling	O
+.	O
+
+Certain	O
+other	O
+factors	O
+increased	O
+the	O
+risk	O
+of	O
+a	O
+blood	O
+clot	O
+even	O
+more	O
+,	O
+such	O
+as	O
+having	O
+a	O
+particular	O
+mutation	O
+(	O
+known	O
+as	O
+factor	O
+V	O
+Leiden	O
+)	O
+in	O
+a	O
+gene	O
+involved	O
+in	O
+blood	O
+clotting	O
+,	O
+having	O
+a	O
+body	O
+mass	O
+index	O
+of	O
+more	O
+than	O
+30	O
+kg	O
+/	O
+m2	O
+(	O
+over	O
+30	O
+kg	O
+/	O
+m2	O
+is	O
+defined	O
+as	O
+being	O
+obese	O
+)	O
+,	O
+being	O
+more	O
+than	O
+1	O
+.	O
+90	O
+meters	O
+tall	O
+,	O
+and	O
+using	O
+oral	O
+contraceptives	O
+.	O
+
+All	O
+these	O
+factors	O
+made	O
+the	O
+risk	O
+of	O
+clots	O
+especially	O
+after	O
+air	O
+travel	O
+worse	O
+;	O
+in	O
+addition	O
+,	O
+people	B
+shorter	O
+than	O
+1	O
+.	O
+60	O
+meters	O
+also	O
+had	O
+an	O
+increased	O
+risk	O
+of	O
+thrombosis	O
+after	O
+air	O
+travel	O
+.	O
+
+However	O
+,	O
+it	O
+should	O
+be	O
+borne	O
+in	O
+mind	O
+that	O
+the	O
+number	O
+of	O
+cases	O
+in	O
+each	O
+of	O
+these	O
+various	O
+groups	O
+was	O
+quite	O
+small	O
+,	O
+and	O
+the	O
+overall	O
+risk	O
+of	O
+getting	O
+a	O
+thrombosis	O
+is	O
+still	O
+low	O
+.	O
+
+What	O
+Do	O
+These	O
+Findings	O
+Mean	O
+?	O
+
+Since	O
+the	O
+risks	O
+of	O
+thrombosis	O
+are	O
+increased	O
+for	O
+all	O
+types	O
+of	O
+long	O
+travel	O
+,	O
+it	O
+seems	O
+that	O
+the	O
+main	O
+factor	O
+causing	O
+the	O
+thrombosis	O
+is	O
+immobility	O
+.	O
+
+However	O
+,	O
+since	O
+the	O
+risk	O
+is	O
+even	O
+higher	O
+for	O
+air	O
+travel	O
+,	O
+the	O
+relative	O
+lack	O
+of	O
+oxygen	O
+may	O
+also	O
+play	O
+a	O
+part	O
+.	O
+
+One	O
+interesting	O
+aspect	O
+of	O
+this	O
+study	O
+is	O
+that	O
+the	O
+researchers	O
+used	O
+partners	O
+as	O
+controls	O
+;	O
+in	O
+order	O
+to	O
+be	O
+sure	O
+that	O
+doing	O
+this	O
+did	O
+not	O
+make	O
+the	O
+results	O
+invalid	O
+,	O
+the	O
+researchers	O
+had	O
+to	O
+carefully	O
+adjust	O
+for	O
+differences	O
+between	O
+the	O
+cases	O
+and	O
+controls	O
+,	O
+such	O
+as	O
+the	O
+fact	O
+that	O
+partners	O
+were	O
+generally	O
+of	O
+the	O
+opposite	O
+sex	O
+.	O
+
+In	O
+a	O
+related	O
+Perspective	O
+(	O
+DOI	O
+:	O
+10	O
+.	O
+1371	O
+/	O
+journal	O
+.	O
+pmed	O
+.	O
+0030300	O
+)	O
+,	O
+Kenneth	O
+Rothman	O
+discusses	O
+the	O
+study	O
+further	O
+.	O
+
+Additional	O
+Information	O
+.	O
+
+Please	O
+access	O
+these	O
+Web	O
+sites	O
+via	O
+the	O
+online	O
+version	O
+of	O
+this	O
+summary	O
+at	O
+http	O
+:	O
+/	O
+/	O
+dx	O
+.	O
+doi	O
+.	O
+org	O
+/	O
+10	O
+.	O
+1371	O
+/	O
+journal	O
+.	O
+pmed	O
+.	O
+0030307	O
+.	O
+
+Introduction	O
+
+Interest	O
+in	O
+the	O
+role	O
+of	O
+air	O
+travel	O
+in	O
+the	O
+pathogenesis	O
+of	O
+venous	O
+thrombosis	O
+has	O
+heightened	O
+in	O
+the	O
+past	O
+5	O
+y	O
+[	O
+1	O
+-	O
+5	O
+]	O
+.	O
+
+Venous	O
+thrombosis	O
+was	O
+first	O
+linked	O
+to	O
+air	O
+travel	O
+in	O
+1954	O
+[	O
+6	O
+]	O
+,	O
+and	O
+as	O
+air	O
+travel	O
+has	O
+become	O
+more	O
+and	O
+more	O
+common	O
+,	O
+many	O
+case	O
+reports	O
+and	O
+case	O
+series	O
+have	O
+been	O
+published	O
+since	O
+.	O
+
+Several	O
+clinical	O
+studies	O
+have	O
+shown	O
+an	O
+association	O
+between	O
+air	O
+travel	O
+and	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+.	O
+
+In	O
+a	O
+series	O
+of	O
+individuals	O
+who	O
+died	O
+suddenly	O
+at	O
+Heathrow	O
+Airport	O
+,	O
+death	O
+occurred	O
+far	O
+more	O
+often	O
+in	O
+the	O
+arrival	O
+than	O
+in	O
+the	O
+departure	O
+area	O
+[	O
+7	O
+]	O
+.	O
+
+Two	O
+similar	O
+studies	O
+described	O
+a	O
+"	O
+dose	O
+-	O
+response	O
+"	O
+relation	O
+:	O
+the	O
+risk	O
+of	O
+pulmonary	O
+embolism	O
+in	O
+air	O
+travelers	O
+increased	O
+with	O
+the	O
+distance	O
+traveled	O
+[	O
+5	O
+,	O
+8	O
+]	O
+.	O
+
+A	O
+number	O
+of	O
+case	O
+-	O
+control	O
+studies	O
+,	O
+however	O
+,	O
+have	O
+shown	O
+conflicting	O
+results	O
+[	O
+9	O
+-	O
+11	O
+]	O
+.	O
+
+More	O
+recently	O
+,	O
+a	O
+2	O
+-	O
+fold	O
+increased	O
+risk	O
+in	O
+patients	B
+who	O
+had	O
+traveled	O
+by	O
+air	O
+was	O
+described	O
+in	O
+a	O
+case	O
+-	O
+control	O
+study	O
+among	O
+210	O
+patients	B
+and	O
+210	O
+controls	O
+[	O
+3	O
+]	O
+.	O
+
+A	O
+case	O
+-	O
+crossover	O
+study	O
+based	O
+on	O
+record	O
+linking	O
+in	O
+Australia	O
+described	O
+a	O
+4	O
+-	O
+fold	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+in	O
+the	O
+first	O
+2	O
+wk	O
+after	O
+a	O
+long	O
+-	O
+haul	O
+flight	O
+[	O
+1	O
+]	O
+.	O
+
+In	O
+terms	O
+of	O
+absolute	O
+risk	O
+,	O
+two	O
+studies	O
+found	O
+similar	O
+results	O
+:	O
+one	O
+performed	O
+in	O
+New	O
+Zealand	O
+found	O
+a	O
+frequency	O
+of	O
+1	O
+%	O
+of	O
+venous	O
+thrombosis	O
+in	O
+878	O
+individuals	O
+who	O
+had	O
+traveled	O
+by	O
+air	O
+for	O
+at	O
+least	O
+10	O
+h	O
+[	O
+2	O
+]	O
+,	O
+and	O
+a	O
+German	O
+study	O
+found	O
+venous	O
+thrombotic	O
+events	O
+in	O
+2	O
+.	O
+8	O
+%	O
+of	O
+964	O
+individuals	O
+who	O
+had	O
+traveled	O
+for	O
+more	O
+than	O
+8	O
+h	O
+in	O
+an	O
+airplane	O
+,	O
+as	O
+compared	O
+to	O
+1	O
+%	O
+in	O
+1	O
+,	O
+213	O
+controls	O
+[	O
+4	O
+]	O
+.	O
+
+The	O
+events	O
+in	O
+both	O
+studies	O
+were	O
+mostly	O
+asymptomatic	O
+.	O
+
+The	O
+available	O
+evidence	O
+suggests	O
+that	O
+the	O
+overall	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+is	O
+moderately	O
+increased	O
+after	O
+air	O
+travel	O
+.	O
+
+Nevertheless	O
+,	O
+many	O
+questions	O
+remain	O
+unanswered	O
+:	O
+the	O
+exact	O
+underlying	O
+mechanism	O
+is	O
+still	O
+unknown	O
+,	O
+and	O
+,	O
+related	O
+to	O
+this	O
+,	O
+it	O
+is	O
+not	O
+clear	O
+whether	O
+the	O
+risk	O
+is	O
+increased	O
+after	O
+air	O
+travel	O
+only	O
+or	O
+after	O
+long	O
+-	O
+distance	O
+travel	O
+in	O
+general	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+effect	O
+of	O
+the	O
+combination	O
+of	O
+other	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+and	O
+travel	O
+has	O
+not	O
+yet	O
+been	O
+systematically	O
+studied	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+a	O
+study	O
+by	O
+Martinelli	O
+et	O
+al	O
+.	O
+,	O
+who	O
+found	O
+an	O
+additionally	O
+increased	O
+risk	O
+in	O
+patients	B
+with	O
+thrombophilia	O
+and	O
+patients	B
+who	O
+used	O
+oral	O
+contraceptives	O
+[	O
+3	O
+]	O
+.	O
+
+The	O
+Multiple	O
+Environmental	O
+and	O
+Genetic	O
+Assessment	O
+(	O
+MEGA	O
+)	O
+study	O
+of	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+is	O
+a	O
+large	O
+ongoing	O
+case	O
+-	O
+control	O
+study	O
+aimed	O
+at	O
+assessing	O
+the	O
+combined	O
+effect	O
+of	O
+genetic	O
+and	O
+acquired	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+.	O
+
+Cases	O
+and	O
+control	O
+individuals	O
+are	O
+questioned	O
+about	O
+-	O
+-	O
+among	O
+many	O
+other	O
+items	O
+-	O
+-	O
+travel	O
+that	O
+occurred	O
+shortly	O
+before	O
+the	O
+event	O
+.	O
+
+This	O
+provides	O
+an	O
+opportunity	O
+to	O
+assess	O
+the	O
+effect	O
+of	O
+travel	O
+on	O
+the	O
+risk	O
+of	O
+thrombosis	O
+in	O
+an	O
+unselected	O
+population	O
+,	O
+as	O
+well	O
+as	O
+the	O
+effect	O
+of	O
+the	O
+combination	O
+of	O
+travel	O
+with	O
+several	O
+other	O
+risk	O
+factors	O
+for	O
+thrombosis	O
+.	O
+
+Methods	O
+
+Study	O
+Design	O
+
+Since	O
+March	O
+1999	O
+,	O
+consecutive	O
+patients	B
+younger	O
+than	O
+70	O
+y	O
+with	O
+a	O
+first	O
+deep	O
+-	O
+vein	O
+thrombosis	O
+(	O
+DVT	O
+)	O
+or	O
+pulmonary	O
+embolism	O
+(	O
+PE	O
+)	O
+have	O
+been	O
+identified	O
+at	O
+six	O
+regional	O
+anticoagulation	O
+clinics	O
+in	O
+the	O
+Netherlands	O
+.	O
+
+Anticoagulant	O
+clinics	O
+monitor	O
+the	O
+anticoagulant	O
+therapy	O
+of	O
+all	O
+patients	B
+in	O
+a	O
+well	O
+-	O
+defined	O
+geographical	O
+area	O
+,	O
+allowing	O
+us	O
+to	O
+identify	O
+consecutive	O
+and	O
+unselected	O
+patients	B
+with	O
+thrombosis	O
+.	O
+
+Patients	B
+who	O
+were	O
+unable	O
+to	O
+fill	O
+in	O
+the	O
+questionnaire	O
+(	O
+because	O
+of	O
+language	O
+or	O
+severe	O
+psychiatric	O
+problems	O
+)	O
+,	O
+as	O
+well	O
+as	O
+those	O
+who	O
+died	O
+soon	O
+after	O
+the	O
+venous	O
+thrombosis	O
+or	O
+who	O
+were	O
+in	O
+the	O
+end	O
+stage	O
+of	O
+a	O
+disease	O
+and	O
+for	O
+that	O
+reason	O
+did	O
+not	O
+participate	O
+,	O
+were	O
+not	O
+included	O
+.	O
+
+All	O
+others	O
+were	O
+considered	O
+eligible	O
+.	O
+
+Partners	O
+of	O
+these	O
+patients	B
+were	O
+invited	O
+as	O
+control	O
+individuals	O
+,	O
+and	O
+the	O
+same	O
+exclusion	O
+criteria	O
+were	O
+applied	O
+.	O
+
+All	O
+participants	B
+filled	O
+in	O
+a	O
+detailed	O
+standardized	O
+questionnaire	O
+on	O
+general	O
+demographic	O
+and	O
+anthropomorphic	O
+characteristics	O
+,	O
+as	O
+well	O
+as	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+.	O
+
+The	O
+questionnaire	O
+was	O
+sent	O
+to	O
+all	O
+participants	B
+within	O
+a	O
+few	O
+weeks	O
+after	O
+the	O
+event	O
+and	O
+covered	O
+the	O
+period	O
+of	O
+1	O
+y	O
+prior	O
+to	O
+the	O
+date	O
+of	O
+the	O
+thrombotic	O
+event	O
+(	O
+index	O
+date	O
+)	O
+.	O
+
+When	O
+the	O
+participant	B
+was	O
+unable	O
+to	O
+fill	O
+in	O
+the	O
+questionnaire	O
+we	O
+asked	O
+questions	O
+by	O
+phone	O
+,	O
+using	O
+a	O
+standardized	O
+mini	O
+-	O
+questionnaire	O
+.	O
+
+Three	O
+months	O
+after	O
+the	O
+patients	B
+had	O
+discontinued	O
+their	O
+oral	O
+anticoagulant	O
+therapy	O
+,	O
+they	O
+were	O
+invited	O
+with	O
+their	O
+partners	O
+to	O
+the	O
+anticoagulation	O
+clinic	O
+for	O
+a	O
+blood	O
+sample	O
+.	O
+
+In	O
+those	O
+patients	B
+who	O
+continued	O
+to	O
+take	O
+oral	O
+anticoagulant	O
+therapy	O
+for	O
+more	O
+than	O
+1	O
+y	O
+after	O
+the	O
+event	O
+,	O
+blood	O
+was	O
+drawn	O
+during	O
+therapy	O
+.	O
+
+If	O
+participants	B
+were	O
+unable	O
+to	O
+come	O
+to	O
+the	O
+clinic	O
+,	O
+a	O
+buccal	O
+swab	O
+was	O
+sent	O
+by	O
+mail	O
+to	O
+replace	O
+the	O
+blood	O
+sample	O
+for	O
+DNA	O
+extraction	O
+.	O
+
+The	O
+study	O
+protocol	O
+was	O
+approved	O
+by	O
+the	O
+Ethics	O
+Committee	O
+of	O
+the	O
+Leiden	O
+University	O
+Medical	O
+Center	O
+.	O
+
+Written	O
+informed	O
+consent	O
+was	O
+obtained	O
+from	O
+all	O
+participants	B
+[	O
+12	O
+]	O
+.	O
+
+Validation	O
+Study	O
+of	O
+Thrombosis	O
+Diagnosis	O
+
+Discharge	O
+letters	O
+or	O
+diagnostic	O
+reports	O
+of	O
+the	O
+venous	O
+thrombotic	O
+event	O
+were	O
+obtained	O
+for	O
+a	O
+sample	O
+of	O
+742	O
+patients	B
+who	O
+had	O
+their	O
+first	O
+thrombosis	O
+between	O
+March	O
+1999	O
+and	O
+March	O
+2000	O
+.	O
+
+The	O
+diagnostic	O
+management	O
+of	O
+the	O
+patients	B
+was	O
+compared	O
+to	O
+the	O
+diagnostic	O
+procedure	O
+as	O
+described	O
+in	O
+the	O
+Dutch	O
+consensus	O
+[	O
+13	O
+]	O
+.	O
+
+Diagnosis	O
+of	O
+clinically	O
+suspected	O
+DVT	O
+of	O
+the	O
+leg	O
+is	O
+based	O
+on	O
+a	O
+clinical	O
+score	O
+,	O
+serial	O
+compression	O
+ultrasonography	O
+,	O
+and	O
+D	O
+-	O
+dimer	O
+assay	O
+.	O
+
+Objective	O
+testing	O
+of	O
+clinically	O
+suspected	O
+pulmonary	O
+embolism	O
+is	O
+based	O
+on	O
+perfusion	O
+and	O
+ventilation	O
+scintigraphy	O
+,	O
+ultrasonography	O
+of	O
+the	O
+leg	O
+veins	O
+,	O
+pulmonary	O
+angiography	O
+,	O
+or	O
+helical	O
+computed	O
+tomography	O
+.	O
+
+Out	O
+of	O
+395	O
+patients	B
+with	O
+DVT	O
+of	O
+the	O
+leg	O
+,	O
+384	O
+(	O
+97	O
+%	O
+)	O
+were	O
+objectively	O
+diagnosed	O
+,	O
+while	O
+out	O
+of	O
+347	O
+patients	B
+with	O
+PE	O
+,	O
+271	O
+(	O
+78	O
+%	O
+)	O
+were	O
+confirmed	O
+with	O
+objective	O
+testing	O
+as	O
+certainly	O
+having	O
+PE	O
+.	O
+
+Since	O
+the	O
+diagnosis	O
+appears	O
+to	O
+be	O
+made	O
+by	O
+objective	O
+methods	O
+in	O
+virtually	O
+all	O
+cases	O
+of	O
+DVT	O
+,	O
+while	O
+being	O
+more	O
+ambiguous	O
+for	O
+PE	O
+,	O
+we	O
+also	O
+analyzed	O
+these	O
+two	O
+manifestations	O
+of	O
+venous	O
+thrombosis	O
+separately	O
+.	O
+
+Current	O
+Analysis	O
+
+For	O
+the	O
+current	O
+analysis	O
+we	O
+were	O
+interested	O
+in	O
+the	O
+effects	O
+of	O
+travel	O
+,	O
+and	O
+its	O
+combined	O
+effect	O
+with	O
+other	O
+common	O
+risk	O
+factors	O
+for	O
+venous	O
+thrombosis	O
+.	O
+
+Patients	B
+with	O
+a	O
+solitary	O
+arm	O
+thrombosis	O
+were	O
+excluded	O
+from	O
+this	O
+analysis	O
+.	O
+
+Of	O
+3	O
+,	O
+902	O
+eligible	O
+cases	O
+,	O
+diagnosed	O
+up	O
+to	O
+May	O
+2002	O
+,	O
+656	O
+did	O
+not	O
+participate	O
+for	O
+various	O
+reasons	O
+(	O
+such	O
+as	O
+not	O
+willing	O
+or	O
+not	O
+reachable	O
+)	O
+,	O
+leading	O
+to	O
+a	O
+response	O
+of	O
+83	O
+%	O
+.	O
+
+A	O
+further	O
+3	O
+%	O
+responded	O
+only	O
+to	O
+the	O
+mini	O
+-	O
+questionnaire	O
+,	O
+taken	O
+by	O
+phone	O
+,	O
+which	O
+did	O
+not	O
+contain	O
+questions	O
+about	O
+travel	O
+.	O
+
+Of	O
+the	O
+remaining	O
+3	O
+,	O
+111	O
+cases	O
+,	O
+78	O
+%	O
+had	O
+a	O
+partner	O
+,	O
+77	O
+%	O
+of	O
+whom	O
+were	O
+willing	O
+to	O
+participate	O
+,	O
+which	O
+left	O
+1	O
+,	O
+867	O
+couples	O
+.	O
+
+Additionally	O
+,	O
+229	O
+partners	O
+were	O
+identified	O
+for	O
+whom	O
+the	O
+corresponding	O
+patient	B
+originally	O
+participated	O
+but	O
+was	O
+later	O
+found	O
+not	O
+to	O
+be	O
+eligible	O
+(	O
+aged	O
+over	O
+70	O
+y	O
+,	O
+or	O
+not	O
+a	O
+first	O
+thrombotic	O
+event	O
+)	O
+.	O
+
+These	O
+control	O
+individuals	O
+were	O
+matched	O
+on	O
+sex	O
+and	O
+5	O
+-	O
+y	O
+age	O
+groups	O
+to	O
+one	O
+of	O
+the	O
+557	O
+patients	B
+whose	O
+partner	O
+did	O
+not	O
+want	O
+to	O
+participate	O
+,	O
+so	O
+an	O
+extra	O
+229	O
+pairs	O
+were	O
+included	O
+,	O
+making	O
+a	O
+total	O
+of	O
+4	O
+,	O
+192	O
+participants	B
+(	O
+2	O
+,	O
+096	O
+pairs	O
+)	O
+.	O
+
+As	O
+part	O
+of	O
+the	O
+general	O
+questionnaire	O
+,	O
+questions	O
+had	O
+been	O
+asked	O
+about	O
+whether	O
+or	O
+not	O
+respondents	O
+had	O
+traveled	O
+for	O
+more	O
+than	O
+4	O
+h	O
+in	O
+the	O
+3	O
+mo	O
+before	O
+the	O
+index	O
+date	O
+,	O
+about	O
+the	O
+travel	O
+date	O
+,	O
+and	O
+about	O
+mode	O
+and	O
+duration	O
+of	O
+travel	O
+.	O
+
+We	O
+assessed	O
+the	O
+occurrence	O
+of	O
+thrombosis	O
+in	O
+relation	O
+to	O
+the	O
+period	O
+of	O
+time	O
+that	O
+had	O
+passed	O
+since	O
+traveling	O
+.	O
+
+Travel	O
+was	O
+defined	O
+in	O
+the	O
+analysis	O
+as	O
+at	O
+least	O
+one	O
+journey	O
+with	O
+a	O
+duration	O
+of	O
+at	O
+least	O
+four	O
+uninterrupted	O
+hours	O
+during	O
+the	O
+8	O
+-	O
+wk	O
+period	O
+before	O
+the	O
+event	O
+.	O
+
+During	O
+the	O
+analysis	O
+it	O
+appeared	O
+that	O
+some	O
+individuals	O
+had	O
+provided	O
+dates	O
+of	O
+travel	O
+after	O
+the	O
+event	O
+instead	O
+of	O
+before	O
+.	O
+
+As	O
+there	O
+was	O
+only	O
+one	O
+opportunity	O
+to	O
+fill	O
+in	O
+such	O
+a	O
+date	O
+,	O
+we	O
+had	O
+no	O
+information	O
+about	O
+the	O
+period	O
+before	O
+the	O
+event	O
+.	O
+
+This	O
+was	O
+the	O
+case	O
+in	O
+88	O
+cases	O
+and	O
+146	O
+controls	O
+.	O
+
+We	O
+excluded	O
+these	O
+individuals	O
+and	O
+their	O
+partners	O
+,	O
+which	O
+left	O
+3	O
+,	O
+812	O
+participants	B
+(	O
+1	O
+,	O
+906	O
+pairs	O
+)	O
+for	O
+the	O
+analysis	O
+.	O
+
+Because	O
+we	O
+selected	O
+the	O
+partners	O
+of	O
+the	O
+cases	O
+as	O
+control	O
+individuals	O
+,	O
+and	O
+because	O
+it	O
+turned	O
+out	O
+,	O
+as	O
+expected	O
+,	O
+that	O
+couples	O
+tend	O
+to	O
+travel	O
+together	O
+,	O
+we	O
+performed	O
+a	O
+conditional	O
+logistic	O
+regression	O
+analysis	O
+to	O
+calculate	O
+odds	O
+ratios	O
+(	O
+ORs	O
+)	O
+for	O
+the	O
+relation	O
+between	O
+travel	O
+and	O
+venous	O
+thrombosis	O
+.	O
+
+This	O
+method	O
+fully	O
+takes	O
+this	O
+matching	O
+into	O
+account	O
+,	O
+and	O
+leads	O
+to	O
+unbiased	O
+estimates	O
+,	O
+with	O
+adjustment	O
+for	O
+all	O
+factors	O
+in	O
+which	O
+cases	O
+and	O
+controls	O
+tend	O
+to	O
+be	O
+similar	O
+,	O
+e	O
+.	O
+g	O
+.	O
+,	O
+socioeconomic	O
+class	O
+[	O
+14	O
+]	O
+.	O
+
+Details	O
+of	O
+this	O
+method	O
+can	O
+be	O
+found	O
+in	O
+Protocol	O
+S1	O
+.	O
+
+The	O
+95	O
+%	O
+confidence	O
+intervals	O
+(	O
+CIs	O
+)	O
+were	O
+derived	O
+from	O
+the	O
+model	O
+.	O
+
+We	O
+assessed	O
+the	O
+combined	O
+effect	O
+of	O
+traveling	O
+and	O
+the	O
+following	O
+risk	O
+factors	O
+for	O
+thrombosis	O
+:	O
+factor	O
+V	O
+Leiden	O
+mutation	O
+,	O
+prothrombin	O
+G20210A	O
+mutation	O
+,	O
+body	O
+mass	O
+index	O
+(	O
+BMI	O
+,	O
+as	O
+kg	O
+/	O
+m2	O
+)	O
+,	O
+and	O
+height	O
+.	O
+
+We	O
+were	O
+also	O
+interested	O
+in	O
+the	O
+combined	O
+effect	O
+of	O
+oral	O
+contraceptive	O
+use	O
+and	O
+travel	O
+.	O
+
+However	O
+,	O
+as	O
+the	O
+control	O
+individuals	O
+were	O
+nearly	O
+always	O
+of	O
+the	O
+opposite	O
+sex	O
+(	O
+partners	O
+of	O
+the	O
+cases	O
+were	O
+recruited	O
+as	O
+controls	O
+)	O
+,	O
+it	O
+was	O
+not	O
+possible	O
+to	O
+perform	O
+a	O
+matched	O
+analysis	O
+for	O
+the	O
+combination	O
+of	O
+oral	O
+contraceptive	O
+use	O
+and	O
+travel	O
+.	O
+
+Therefore	O
+,	O
+we	O
+performed	O
+a	O
+case	O
+-	O
+only	O
+analysis	O
+[	O
+15	O
+]	O
+.	O
+
+This	O
+method	O
+allows	O
+one	O
+to	O
+examine	O
+the	O
+association	O
+between	O
+two	O
+exposures	O
+among	O
+case	O
+individuals	O
+only	O
+.	O
+
+ORs	O
+are	O
+interpreted	O
+as	O
+a	O
+synergy	O
+index	O
+(	O
+SI	O
+)	O
+on	O
+a	O
+multiplicative	O
+scale	O
+,	O
+with	O
+independence	O
+assumed	O
+between	O
+the	O
+exposures	O
+.	O
+
+As	O
+this	O
+analysis	O
+depends	O
+only	O
+on	O
+cases	O
+,	O
+it	O
+was	O
+possible	O
+to	O
+perform	O
+it	O
+in	O
+all	O
+consecutive	O
+cases	O
+,	O
+therefore	O
+also	O
+including	O
+those	O
+without	O
+a	O
+partner	O
+.	O
+
+Laboratory	O
+Measurements	O
+
+Blood	O
+was	O
+collected	O
+from	O
+the	O
+antecubital	O
+vein	O
+into	O
+vacuum	O
+tubes	O
+containing	O
+0	O
+.	O
+106	O
+mol	O
+/	O
+l	O
+trisodium	O
+citrate	O
+.	O
+
+High	O
+molecular	O
+weight	O
+DNA	O
+was	O
+isolated	O
+from	O
+leukocytes	O
+using	O
+a	O
+standard	O
+salting	O
+-	O
+out	O
+procedure	O
+[	O
+16	O
+]	O
+and	O
+stored	O
+at	O
+-	O
+20	O
+degrees	O
+C	O
+.	O
+
+When	O
+a	O
+blood	O
+sample	O
+was	O
+not	O
+available	O
+,	O
+DNA	O
+was	O
+extracted	O
+from	O
+buccal	O
+swabs	O
+.	O
+
+Three	O
+large	O
+cotton	B
+swabs	O
+in	O
+a	O
+total	O
+of	O
+6	O
+ml	O
+of	O
+SDS	O
+-	O
+proteinase	O
+K	O
+solution	O
+(	O
+100	O
+mM	O
+NaCl	O
+,	O
+10	O
+mM	O
+EDTA	O
+,	O
+10	O
+mM	O
+Tris	O
+-	O
+HCl	O
+[	O
+pH	O
+8	O
+.	O
+0	O
+]	O
+,	O
+0	O
+.	O
+5	O
+%	O
+SDS	O
+,	O
+0	O
+.	O
+1	O
+mg	O
+/	O
+ml	O
+proteinase	O
+K	O
+)	O
+were	O
+obtained	O
+.	O
+
+Upon	O
+arrival	O
+,	O
+the	O
+proteinase	O
+K	O
+concentration	O
+was	O
+raised	O
+to	O
+0	O
+.	O
+2	O
+mg	O
+/	O
+ml	O
+,	O
+and	O
+the	O
+sample	O
+was	O
+incubated	O
+for	O
+2	O
+h	O
+at	O
+65	O
+degrees	O
+C	O
+.	O
+
+Subsequently	O
+,	O
+the	O
+solute	O
+was	O
+recovered	O
+by	O
+centrifugation	O
+.	O
+
+Potassium	O
+acetate	O
+was	O
+added	O
+to	O
+the	O
+supernatant	O
+to	O
+a	O
+final	O
+concentration	O
+of	O
+1	O
+.	O
+6	O
+M	O
+.	O
+
+After	O
+15	O
+min	O
+incubation	O
+on	O
+ice	O
+,	O
+proteins	O
+were	O
+removed	O
+using	O
+chloroform	O
+/	O
+isomylalcohol	O
+(	O
+24	O
+:	O
+1	O
+)	O
+treatment	O
+.	O
+
+The	O
+DNA	O
+in	O
+the	O
+water	O
+phase	O
+was	O
+subsequently	O
+ethanol	O
+precipitated	O
+.	O
+
+After	O
+centrifugation	O
+,	O
+the	O
+pellet	O
+was	O
+resuspended	O
+in	O
+200	O
+mu	O
+l	O
+of	O
+10	O
+mM	O
+Tris	O
+-	O
+HCl	O
+and	O
+10	O
+mM	O
+EDTA	O
+(	O
+pH	O
+8	O
+.	O
+0	O
+)	O
+,	O
+and	O
+frozen	O
+at	O
+-	O
+20	O
+degrees	O
+C	O
+until	O
+further	O
+analysis	O
+.	O
+
+The	O
+factor	O
+V	O
+Leiden	O
+mutation	O
+(	O
+G1691A	O
+)	O
+and	O
+the	O
+prothrombin	O
+mutation	O
+(	O
+G20210A	O
+)	O
+were	O
+simultaneously	O
+detected	O
+by	O
+duplex	O
+polymerase	O
+chain	O
+reaction	O
+[	O
+17	O
+,	O
+18	O
+]	O
+.	O
+
+The	O
+technician	O
+was	O
+blinded	O
+concerning	O
+the	O
+origin	O
+of	O
+the	O
+sample	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+whether	O
+it	O
+was	O
+from	O
+a	O
+patient	B
+or	O
+from	O
+a	O
+control	O
+individual	O
+.	O
+
+Results	O
+
+Venous	O
+Thrombosis	O
+in	O
+Relation	O
+to	O
+Travel	O
+
+Table	O
+1	O
+shows	O
+general	O
+characteristics	O
+of	O
+the	O
+1	O
+,	O
+906	O
+patients	B
+.	O
+
+They	O
+ranged	O
+in	O
+age	O
+from	O
+18	O
+to	O
+69	O
+y	O
+(	O
+median	O
+50	O
+.	O
+4	O
+y	O
+)	O
+;	O
+51	O
+%	O
+were	O
+men	B
+.	O
+
+Diagnosis	O
+was	O
+DVT	O
+in	O
+57	O
+%	O
+of	O
+the	O
+cases	O
+,	O
+PE	O
+in	O
+32	O
+%	O
+,	O
+and	O
+both	O
+in	O
+11	O
+%	O
+.	O
+
+As	O
+partners	O
+of	O
+the	O
+cases	O
+were	O
+included	O
+as	O
+control	O
+individuals	O
+,	O
+the	O
+sex	O
+distribution	O
+of	O
+the	O
+control	O
+individuals	O
+was	O
+the	O
+opposite	O
+;	O
+the	O
+age	O
+distribution	O
+differed	O
+only	O
+trivially	O
+.	O
+
+Of	O
+the	O
+patients	B
+,	O
+233	O
+individuals	O
+(	O
+12	O
+%	O
+)	O
+had	O
+traveled	O
+for	O
+at	O
+least	O
+4	O
+h	O
+by	O
+air	O
+,	O
+bus	O
+,	O
+car	O
+,	O
+or	O
+train	O
+within	O
+the	O
+8	O
+wk	O
+preceding	O
+the	O
+index	O
+date	O
+,	O
+as	O
+compared	O
+to	O
+182	O
+of	O
+the	O
+control	O
+individuals	O
+(	O
+9	O
+.	O
+5	O
+%	O
+)	O
+.	O
+
+As	O
+the	O
+cases	O
+and	O
+control	O
+individuals	O
+were	O
+selected	O
+as	O
+couples	O
+,	O
+many	O
+pairs	O
+(	O
+135	O
+)	O
+had	O
+traveled	O
+together	O
+and	O
+were	O
+uninformative	O
+:	O
+as	O
+a	O
+consequence	O
+,	O
+145	O
+pairs	O
+in	O
+which	O
+either	O
+the	O
+patient	B
+(	O
+98	O
+)	O
+or	O
+the	O
+control	O
+(	O
+47	O
+)	O
+had	O
+traveled	O
+could	O
+be	O
+used	O
+for	O
+the	O
+matched	O
+analysis	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+This	O
+analysis	O
+showed	O
+a	O
+2	O
+-	O
+fold	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+for	O
+all	O
+modes	O
+of	O
+travel	O
+combined	O
+(	O
+OR	O
+2	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+5	O
+-	O
+3	O
+.	O
+0	O
+)	O
+compared	O
+to	O
+not	O
+traveling	O
+.	O
+
+For	O
+air	O
+travel	O
+alone	O
+,	O
+49	O
+individuals	O
+(	O
+31	O
+cases	O
+and	O
+18	O
+controls	O
+)	O
+had	O
+traveled	O
+without	O
+their	O
+partner	O
+,	O
+and	O
+the	O
+analysis	O
+yielded	O
+an	O
+OR	O
+of	O
+1	O
+.	O
+7	O
+(	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+0	O
+-	O
+3	O
+.	O
+1	O
+)	O
+.	O
+
+For	O
+the	O
+other	O
+modes	O
+of	O
+travel	O
+(	O
+car	O
+,	O
+bus	O
+,	O
+and	O
+train	O
+)	O
+the	O
+relative	O
+risks	O
+were	O
+essentially	O
+similar	O
+to	O
+each	O
+other	O
+and	O
+to	O
+that	O
+of	O
+air	O
+travel	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+The	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+was	O
+not	O
+clearly	O
+related	O
+to	O
+increased	O
+duration	O
+of	O
+travel	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Of	O
+the	O
+233	O
+events	O
+that	O
+occurred	O
+within	O
+8	O
+wk	O
+after	O
+traveling	O
+,	O
+68	O
+(	O
+29	O
+%	O
+)	O
+were	O
+diagnosed	O
+in	O
+the	O
+first	O
+week	O
+,	O
+after	O
+which	O
+the	O
+incidence	O
+gradually	O
+decreased	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+The	O
+Effect	O
+of	O
+Other	O
+Risk	O
+Factors	O
+Combined	O
+with	O
+Travel	O
+
+Prothrombotic	O
+mutations	O
+.	O
+
+Information	O
+on	O
+the	O
+factor	O
+V	O
+Leiden	O
+mutation	O
+and	O
+prothrombin	O
+G20210A	O
+genotype	O
+was	O
+available	O
+for	O
+1	O
+,	O
+713	O
+patients	B
+(	O
+90	O
+%	O
+)	O
+and	O
+for	O
+1	O
+,	O
+629	O
+of	O
+the	O
+control	O
+individuals	O
+(	O
+85	O
+%	O
+)	O
+.	O
+
+Factor	O
+V	O
+Leiden	O
+was	O
+present	O
+in	O
+259	O
+cases	O
+(	O
+14	O
+%	O
+)	O
+and	O
+84	O
+control	O
+individuals	O
+(	O
+4	O
+%	O
+)	O
+(	O
+OR	O
+3	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+2	O
+.	O
+4	O
+-	O
+4	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+was	O
+8	O
+-	O
+fold	O
+increased	O
+in	O
+people	B
+with	O
+factor	O
+V	O
+Leiden	O
+who	O
+had	O
+traveled	O
+by	O
+bus	O
+,	O
+car	O
+,	O
+or	O
+train	O
+(	O
+modes	O
+combined	O
+)	O
+as	O
+compared	O
+to	O
+noncarriers	O
+who	O
+did	O
+not	O
+travel	O
+(	O
+OR	O
+8	O
+.	O
+1	O
+;	O
+95	O
+%	O
+CI	O
+2	O
+.	O
+7	O
+-	O
+24	O
+.	O
+7	O
+)	O
+.	O
+
+For	O
+the	O
+combined	O
+effect	O
+of	O
+air	O
+travel	O
+and	O
+factor	O
+V	O
+Leiden	O
+,	O
+the	O
+risk	O
+seemed	O
+even	O
+slightly	O
+higher	O
+(	O
+OR	O
+13	O
+.	O
+6	O
+;	O
+95	O
+%	O
+CI	O
+2	O
+.	O
+9	O
+-	O
+64	O
+.	O
+2	O
+)	O
+.	O
+
+The	O
+prothrombin	O
+G20210A	O
+mutation	O
+was	O
+found	O
+in	O
+83	O
+cases	O
+(	O
+4	O
+%	O
+)	O
+and	O
+in	O
+29	O
+control	O
+individuals	O
+(	O
+2	O
+%	O
+)	O
+(	O
+OR	O
+2	O
+.	O
+7	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+7	O
+-	O
+4	O
+.	O
+2	O
+)	O
+.	O
+
+The	O
+risk	O
+in	O
+individuals	O
+with	O
+this	O
+mutation	O
+who	O
+had	O
+traveled	O
+was	O
+difficult	O
+to	O
+interpret	O
+because	O
+of	O
+the	O
+small	O
+numbers	O
+but	O
+appeared	O
+not	O
+to	O
+increase	O
+more	O
+than	O
+additively	O
+(	O
+Table	O
+3	O
+)	O
+.	O
+
+BMI	O
+.	O
+
+The	O
+effect	O
+of	O
+BMI	O
+was	O
+studied	O
+by	O
+dividing	O
+individuals	O
+into	O
+three	O
+categories	O
+with	O
+the	O
+following	O
+BMI	O
+values	O
+:	O
+<	O
+25	O
+,	O
+25	O
+-	O
+30	O
+,	O
+and	O
+>	O
+30	O
+kg	O
+/	O
+m2	O
+[	O
+19	O
+]	O
+.	O
+
+A	O
+BMI	O
+of	O
+25	O
+-	O
+30	O
+kg	O
+/	O
+m2	O
+was	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+(	O
+OR	O
+1	O
+.	O
+4	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+2	O
+-	O
+1	O
+.	O
+7	O
+)	O
+,	O
+and	O
+the	O
+risk	O
+was	O
+slightly	O
+higher	O
+in	O
+patients	B
+with	O
+a	O
+BMI	O
+of	O
+30	O
+kg	O
+/	O
+m2	O
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+more	O
+(	O
+OR	O
+1	O
+.	O
+7	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+4	O
+-	O
+2	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+combined	O
+effect	O
+of	O
+a	O
+higher	O
+BMI	O
+and	O
+travel	O
+was	O
+the	O
+sum	O
+of	O
+the	O
+individual	O
+risks	O
+(	O
+Table	O
+3	O
+)	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+people	B
+with	O
+a	O
+BMI	O
+of	O
+more	O
+than	O
+30	O
+kg	O
+/	O
+m2	O
+who	O
+traveled	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+,	O
+for	O
+whom	O
+the	O
+risk	O
+was	O
+10	O
+-	O
+fold	O
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+(	O
+OR	O
+9	O
+.	O
+9	O
+;	O
+95	O
+%	O
+CI	O
+3	O
+.	O
+6	O
+-	O
+27	O
+.	O
+6	O
+)	O
+.	O
+
+This	O
+increase	O
+in	O
+risk	O
+was	O
+not	O
+found	O
+in	O
+people	B
+who	O
+traveled	O
+by	O
+air	O
+.	O
+
+Height	O
+.	O
+
+Particularly	O
+short	O
+or	O
+tall	O
+people	B
+may	O
+be	O
+subjected	O
+during	O
+travel	O
+to	O
+even	O
+more	O
+unnatural	O
+sitting	O
+positions	O
+than	O
+individuals	O
+with	O
+average	O
+height	O
+.	O
+
+Therefore	O
+,	O
+we	O
+assessed	O
+the	O
+effect	O
+of	O
+extremes	O
+of	O
+heights	O
+in	O
+combination	O
+with	O
+travel	O
+on	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+by	O
+comparing	O
+short	O
+(	O
+less	O
+than	O
+1	O
+.	O
+60	O
+m	O
+)	O
+and	O
+tall	O
+individuals	O
+(	O
+more	O
+than	O
+1	O
+.	O
+90	O
+m	O
+)	O
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+people	B
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+height	O
+(	O
+1	O
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+60	O
+-	O
+1	O
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+90	O
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+)	O
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+
+Compared	O
+to	O
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+,	O
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+of	O
+venous	O
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+lower	O
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+(	O
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+0	O
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+7	O
+;	O
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+0	O
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+5	O
+-	O
+0	O
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+9	O
+)	O
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+did	O
+not	O
+differ	O
+for	O
+very	O
+tall	O
+individuals	O
+(	O
+OR	O
+0	O
+.	O
+9	O
+;	O
+95	O
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+CI	O
+0	O
+.	O
+7	O
+-	O
+1	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+risk	O
+was	O
+found	O
+to	O
+be	O
+increased	O
+in	O
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+than	O
+1	O
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+90	O
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+who	O
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+(	O
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+4	O
+.	O
+7	O
+;	O
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+1	O
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+4	O
+-	O
+15	O
+.	O
+4	O
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+travel	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+;	O
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+6	O
+.	O
+8	O
+;	O
+95	O
+%	O
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+0	O
+.	O
+8	O
+-	O
+60	O
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+6	O
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+air	O
+travel	O
+)	O
+compared	O
+to	O
+non	O
+-	O
+traveling	O
+people	B
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+average	O
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+.	O
+
+Interestingly	O
+,	O
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+risk	O
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+venous	O
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+also	O
+increased	O
+in	O
+short	O
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+but	O
+only	O
+after	O
+air	O
+travel	O
+(	O
+OR	O
+4	O
+.	O
+9	O
+;	O
+95	O
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+0	O
+.	O
+9	O
+-	O
+25	O
+.	O
+6	O
+)	O
+,	O
+not	O
+after	O
+other	O
+modes	O
+of	O
+travel	O
+(	O
+OR	O
+1	O
+.	O
+0	O
+;	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+3	O
+-	O
+2	O
+.	O
+8	O
+,	O
+all	O
+relative	O
+to	O
+non	O
+-	O
+traveling	O
+people	B
+of	O
+average	O
+height	O
+)	O
+.	O
+
+Oral	O
+contraception	O
+.	O
+
+To	O
+study	O
+the	O
+association	O
+between	O
+oral	O
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+use	O
+,	O
+travel	O
+,	O
+and	O
+the	O
+risk	O
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+venous	O
+thrombosis	O
+,	O
+we	O
+performed	O
+a	O
+case	O
+-	O
+only	O
+analysis	O
+in	O
+all	O
+female	O
+patients	B
+who	O
+were	O
+less	O
+than	O
+50	O
+y	O
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+age	O
+.	O
+
+As	O
+we	O
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+only	O
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+,	O
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+was	O
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+to	O
+include	O
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+this	O
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+,	O
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+1	O
+,	O
+025	O
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+.	O
+
+Non	O
+-	O
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+who	O
+did	O
+not	O
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+as	O
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+reference	O
+group	O
+.	O
+
+The	O
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+-	O
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+estimate	O
+of	O
+the	O
+SI	O
+for	O
+women	B
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+,	O
+bus	O
+,	O
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+train	O
+was	O
+2	O
+.	O
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+(	O
+95	O
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+CI	O
+1	O
+.	O
+5	O
+-	O
+3	O
+.	O
+7	O
+)	O
+.	O
+
+This	O
+indicates	O
+that	O
+the	O
+OR	O
+for	O
+the	O
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+travel	O
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+oral	O
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+.	O
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+the	O
+product	O
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+the	O
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+.	O
+
+As	O
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+generally	O
+increases	O
+the	O
+risk	O
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+venous	O
+thrombosis	O
+about	O
+4	O
+-	O
+fold	O
+[	O
+20	O
+]	O
+,	O
+the	O
+combination	O
+with	O
+travel	O
+by	O
+car	O
+,	O
+bus	O
+,	O
+or	O
+train	O
+would	O
+lead	O
+to	O
+an	O
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+about	O
+20	O
+(	O
+4	O
+x	O
+2	O
+x	O
+2	O
+.	O
+4	O
+)	O
+.	O
+
+A	O
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+stronger	O
+interaction	O
+of	O
+travel	O
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+found	O
+:	O
+the	O
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+-	O
+only	O
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+the	O
+SI	O
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+4	O
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+9	O
+(	O
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+%	O
+CI	O
+2	O
+.	O
+1	O
+-	O
+11	O
+.	O
+4	O
+)	O
+,	O
+which	O
+would	O
+result	O
+in	O
+an	O
+OR	O
+of	O
+about	O
+40	O
+(	O
+4	O
+x	O
+2	O
+x	O
+4	O
+.	O
+9	O
+)	O
+.	O
+
+Effect	O
+of	O
+Risk	O
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+in	O
+DVT	O
+Patients	B
+Only	O
+
+Of	O
+the	O
+1	O
+,	O
+906	O
+cases	O
+,	O
+1	O
+,	O
+082	O
+were	O
+diagnosed	O
+with	O
+DVT	O
+.	O
+
+As	O
+the	O
+diagnosis	O
+was	O
+more	O
+unambiguous	O
+in	O
+these	O
+patients	B
+(	O
+97	O
+%	O
+objectively	O
+diagnosed	O
+as	O
+compared	O
+to	O
+78	O
+%	O
+of	O
+the	O
+PE	O
+patients	B
+)	O
+,	O
+we	O
+repeated	O
+the	O
+analysis	O
+in	O
+these	O
+patients	B
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+
+In	O
+this	O
+analysis	O
+,	O
+the	O
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+of	O
+travel	O
+on	O
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+to	O
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+(	O
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+)	O
+.	O
+
+However	O
+,	O
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+(	O
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+3	O
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+0	O
+;	O
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+1	O
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+3	O
+-	O
+7	O
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+1	O
+)	O
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+travel	O
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+,	O
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+,	O
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+(	O
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+1	O
+.	O
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+;	O
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+1	O
+.	O
+1	O
+-	O
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+)	O
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+Table	O
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+)	O
+.	O
+
+Also	O
+,	O
+the	O
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+travel	O
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+in	O
+more	O
+clear	O
+-	O
+cut	O
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+,	O
+despite	O
+the	O
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+,	O
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+the	O
+prothrombin	O
+G20210A	O
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+did	O
+not	O
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+(	O
+Table	O
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+)	O
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+
+Furthermore	O
+,	O
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+more	O
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+in	O
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+DVT	O
+both	O
+in	O
+people	B
+who	O
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+,	O
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+,	O
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+train	O
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+in	O
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+who	O
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+.	O
+
+Being	O
+more	O
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+1	O
+.	O
+90	O
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+travel	O
+resulted	O
+in	O
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+;	O
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+was	O
+more	O
+increased	O
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+travel	O
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+air	O
+(	O
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+6	O
+.	O
+8	O
+;	O
+95	O
+%	O
+CI	O
+1	O
+.	O
+1	O
+-	O
+43	O
+.	O
+5	O
+)	O
+(	O
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+4	O
+)	O
+.	O
+
+The	O
+effect	O
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+in	O
+combination	O
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+travel	O
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+,	O
+bus	O
+,	O
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+women	B
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+was	O
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+(	O
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+-	O
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+.	O
+2	O
+)	O
+.	O
+
+In	O
+those	O
+who	O
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+air	O
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+was	O
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+(	O
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+3	O
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+4	O
+;	O
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+1	O
+.	O
+3	O
+-	O
+8	O
+.	O
+8	O
+)	O
+,	O
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+indicative	O
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+strong	O
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+effect	O
+.	O
+
+Discussion	O
+
+In	O
+this	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+,	O
+long	O
+-	O
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+venous	O
+thrombosis	O
+2	O
+-	O
+fold	O
+.	O
+
+Travel	O
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+air	O
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+risk	O
+to	O
+the	O
+same	O
+extent	O
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+travel	O
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+car	O
+,	O
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+,	O
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+.	O
+
+The	O
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+week	O
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+.	O
+
+As	O
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+which	O
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+(	O
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+)	O
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+[	O
+21	O
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+,	O
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+in	O
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+.	O
+
+This	O
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+,	O
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+,	O
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+,	O
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+.	O
+
+Some	O
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+air	O
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+.	O
+
+Although	O
+the	O
+studies	O
+that	O
+have	O
+been	O
+published	O
+so	O
+far	O
+have	O
+not	O
+yielded	O
+entirely	O
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+results	O
+,	O
+those	O
+that	O
+did	O
+report	O
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+increased	O
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+venous	O
+thrombosis	O
+in	O
+air	O
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+showed	O
+similar	O
+risk	O
+estimates	O
+of	O
+a	O
+2	O
+-	O
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+3	O
+-	O
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+(	O
+even	O
+in	O
+one	O
+with	O
+asymptomatic	O
+events	O
+only	O
+[	O
+4	O
+]	O
+)	O
+.	O
+
+The	O
+occurrence	O
+of	O
+venous	O
+thrombosis	O
+was	O
+highest	O
+in	O
+the	O
+first	O
+week	O
+after	O
+travel	O
+,	O
+and	O
+slowly	O
+declined	O
+afterwards	O
+,	O
+a	O
+pattern	O
+that	O
+was	O
+also	O
+described	O
+in	O
+a	O
+recent	O
+record	O
+-	O
+linking	O
+study	O
+from	O
+Australia	O
+[	O
+1	O
+]	O
+,	O
+supporting	O
+a	O
+causal	O
+relation	O
+.	O
+
+As	O
+a	O
+possible	O
+mechanism	O
+for	O
+an	O
+extra	O
+risk	O
+in	O
+travelers	O
+who	O
+fly	O
+,	O
+an	O
+effect	O
+of	O
+hypobaric	O
+hypoxia	O
+on	O
+the	O
+coagulation	O
+system	O
+was	O
+postulated	O
+,	O
+which	O
+has	O
+already	O
+been	O
+studied	O
+a	O
+number	O
+of	O
+times	O
+,	O
+mainly	O
+in	O
+hypobaric	O
+chambers	O
+,	O
+with	O
+unclear	O
+results	O
+so	O
+far	O
+.	O
+
+Our	O
+study	O
+showed	O
+an	O
+increased	O
+risk	O
+in	O
+all	O
+types	O
+of	O
+travel	O
+,	O
+which	O
+suggests	O
+that	O
+the	O
+increased	O
+risk	O
+of	O
+flying	O
+is	O
+caused	O
+mainly	O
+by	O
+immobilization	O
+.	O
+
+Additionally	O
+,	O
+the	O
+risk	O
+is	O
+further	O
+increased	O
+in	O
+short	O
+and	O
+tall	O
+people	B
+,	O
+who	O
+are	O
+likely	O
+to	O
+experience	O
+more	O
+immobilization	O
+and	O
+venous	O
+compression	O
+than	O
+other	O
+travelers	O
+.	O
+
+However	O
+,	O
+as	O
+some	O
+of	O
+our	O
+findings	O
+were	O
+more	O
+pronounced	O
+for	O
+air	O
+travel	O
+,	O
+we	O
+cannot	O
+exclude	O
+an	O
+additional	O
+effect	O
+of	O
+hypobaric	O
+hypoxia	O
+,	O
+possibly	O
+in	O
+risk	O
+groups	O
+only	O
+.	O
+
+This	O
+possibility	O
+is	O
+supported	O
+by	O
+a	O
+recent	O
+study	O
+of	O
+our	O
+group	O
+[	O
+22	O
+]	O
+in	O
+which	O
+we	O
+found	O
+that	O
+thrombin	O
+generation	O
+occurred	O
+in	O
+some	O
+healthy	O
+volunteers	O
+after	O
+flying	O
+for	O
+8	O
+h	O
+but	O
+happened	O
+to	O
+a	O
+far	O
+lesser	O
+extent	O
+after	O
+being	O
+immobilized	O
+for	O
+8	O
+h	O
+in	O
+a	O
+cinema	O
+.	O
+
+The	O
+high	O
+response	O
+in	O
+the	O
+fliers	O
+was	O
+associated	O
+with	O
+the	O
+presence	O
+of	O
+risk	O
+factors	O
+for	O
+thrombosis	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+oral	O
+contraceptive	O
+use	O
+,	O
+the	O
+factor	O
+V	O
+Leiden	O
+mutation	O
+,	O
+and	O
+the	O
+combination	O
+of	O
+the	O
+two	O
+.	O
+
+This	O
+finding	O
+indicates	O
+an	O
+effect	O
+of	O
+an	O
+additional	O
+factor	O
+in	O
+an	O
+airplane	O
+,	O
+such	O
+as	O
+hypobaric	O
+hypoxia	O
+,	O
+to	O
+which	O
+mainly	O
+individuals	O
+with	O
+risk	O
+factors	O
+respond	O
+.	O
+
+None	O
+of	O
+the	O
+studies	O
+published	O
+so	O
+far	O
+have	O
+systematically	O
+studied	O
+the	O
+effect	O
+of	O
+traveling	O
+in	O
+combination	O
+with	O
+other	O
+risk	O
+factors	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+the	O
+study	O
+by	O
+Martinelli	O
+et	O
+al	O
+.	O
+
+[	O
+3	O
+]	O
+.	O
+
+In	O
+an	O
+analysis	O
+of	O
+210	O
+patients	B
+,	O
+they	O
+found	O
+a	O
+16	O
+-	O
+fold	O
+increased	O
+risk	O
+for	O
+patients	B
+who	O
+traveled	O
+by	O
+air	O
+and	O
+had	O
+some	O
+form	O
+of	O
+thrombophilia	O
+,	O
+as	O
+well	O
+as	O
+a	O
+14	O
+-	O
+fold	O
+increased	O
+risk	O
+in	O
+women	B
+who	O
+flew	O
+and	O
+used	O
+oral	O
+contraceptives	O
+,	O
+findings	O
+that	O
+confirm	O
+both	O
+the	O
+results	O
+of	O
+the	O
+present	O
+study	O
+and	O
+our	O
+finding	O
+of	O
+activated	O
+coagulation	O
+in	O
+individuals	O
+with	O
+risk	O
+factors	O
+after	O
+flying	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+finding	O
+that	O
+taller	O
+and	O
+shorter	O
+people	B
+had	O
+an	O
+increased	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+after	O
+traveling	O
+should	O
+be	O
+interpreted	O
+with	O
+some	O
+caution	O
+,	O
+as	O
+the	O
+numbers	O
+were	O
+small	O
+in	O
+these	O
+strata	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+it	O
+is	O
+biologically	O
+plausible	O
+:	O
+very	O
+tall	O
+people	B
+are	O
+subjected	O
+to	O
+even	O
+more	O
+cramped	O
+seating	O
+than	O
+average	O
+-	O
+height	O
+individuals	O
+,	O
+and	O
+very	O
+short	O
+people	B
+'	O
+s	O
+feet	O
+may	O
+not	O
+touch	O
+the	O
+floor	O
+,	O
+which	O
+would	O
+lead	O
+to	O
+extra	O
+compression	O
+of	O
+the	O
+popliteal	O
+veins	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+increased	O
+risk	O
+for	O
+short	O
+people	B
+was	O
+only	O
+found	O
+in	O
+people	B
+who	O
+traveled	O
+by	O
+air	O
+.	O
+
+This	O
+may	O
+have	O
+to	O
+do	O
+with	O
+the	O
+fact	O
+that	O
+seats	O
+in	O
+cars	O
+are	O
+generally	O
+lower	O
+,	O
+and	O
+more	O
+individually	O
+adjustable	O
+,	O
+than	O
+those	O
+in	O
+airplanes	O
+.	O
+
+As	O
+the	O
+diagnosis	O
+of	O
+DVT	O
+is	O
+usually	O
+more	O
+unambiguous	O
+than	O
+that	O
+of	O
+PE	O
+[	O
+23	O
+]	O
+,	O
+as	O
+was	O
+the	O
+case	O
+in	O
+our	O
+study	O
+population	O
+as	O
+well	O
+,	O
+we	O
+repeated	O
+the	O
+analysis	O
+using	O
+only	O
+DVT	O
+as	O
+the	O
+outcome	O
+of	O
+interest	O
+(	O
+97	O
+%	O
+objectively	O
+diagnosed	O
+)	O
+.	O
+
+In	O
+this	O
+analysis	O
+,	O
+despite	O
+using	O
+smaller	O
+numbers	O
+,	O
+most	O
+findings	O
+were	O
+either	O
+similar	O
+or	O
+appeared	O
+more	O
+evident	O
+,	O
+and	O
+inconsistencies	O
+that	O
+were	O
+found	O
+when	O
+using	O
+both	O
+DVT	O
+and	O
+PE	O
+as	O
+endpoints	O
+disappeared	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+first	O
+large	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+in	O
+which	O
+the	O
+effect	O
+of	O
+travel	O
+on	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+has	O
+been	O
+studied	O
+.	O
+
+Because	O
+the	O
+control	O
+individuals	O
+were	O
+closely	O
+matched	O
+,	O
+being	O
+partners	O
+of	O
+the	O
+cases	O
+,	O
+and	O
+couples	O
+tend	O
+to	O
+travel	O
+together	O
+,	O
+only	O
+the	O
+cases	O
+and	O
+control	O
+individuals	O
+who	O
+had	O
+not	O
+traveled	O
+together	O
+could	O
+be	O
+used	O
+for	O
+the	O
+analysis	O
+.	O
+
+Also	O
+because	O
+of	O
+this	O
+design	O
+,	O
+the	O
+effect	O
+of	O
+sex	O
+and	O
+age	O
+could	O
+not	O
+be	O
+studied	O
+.	O
+
+It	O
+has	O
+to	O
+be	O
+noted	O
+,	O
+however	O
+,	O
+that	O
+for	O
+all	O
+other	O
+research	O
+questions	O
+on	O
+the	O
+effect	O
+of	O
+genetic	O
+and	O
+acquired	O
+risk	O
+factors	O
+on	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+,	O
+this	O
+design	O
+has	O
+no	O
+limitations	O
+and	O
+the	O
+close	O
+matching	O
+of	O
+cases	O
+and	O
+controls	O
+renders	O
+confounding	O
+by	O
+,	O
+for	O
+instance	O
+,	O
+lifestyle	O
+and	O
+socioeconomic	O
+class	O
+less	O
+likely	O
+than	O
+in	O
+previous	O
+unmatched	O
+studies	O
+(	O
+see	O
+also	O
+Protocol	O
+S1	O
+)	O
+.	O
+
+Another	O
+advantage	O
+of	O
+this	O
+approach	O
+is	O
+the	O
+minimization	O
+of	O
+recall	O
+bias	O
+,	O
+as	O
+the	O
+cases	O
+and	O
+controls	O
+would	O
+generally	O
+fill	O
+in	O
+the	O
+questionnaire	O
+together	O
+.	O
+
+Many	O
+questions	O
+are	O
+still	O
+left	O
+unanswered	O
+that	O
+necessitate	O
+more	O
+research	O
+.	O
+
+First	O
+of	O
+all	O
+,	O
+our	O
+study	O
+results	O
+apply	O
+only	O
+to	O
+people	B
+younger	O
+than	O
+70	O
+y	O
+of	O
+age	O
+.	O
+
+Furthermore	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+other	O
+characteristics	O
+exist	O
+that	O
+also	O
+increase	O
+the	O
+risk	O
+-	O
+-	O
+person	B
+-	O
+specific	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+other	O
+drug	O
+use	O
+)	O
+,	O
+behavioral	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+use	O
+of	O
+sleeping	O
+pills	O
+or	O
+alcohol	O
+consumption	O
+)	O
+,	O
+and	O
+flight	O
+-	O
+specific	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+class	O
+or	O
+seating	O
+)	O
+-	O
+-	O
+that	O
+need	O
+to	O
+be	O
+identified	O
+.	O
+
+These	O
+further	O
+variables	O
+are	O
+part	O
+of	O
+our	O
+ongoing	O
+study	O
+as	O
+part	O
+of	O
+the	O
+World	O
+Health	O
+Organization	O
+Research	O
+Initiative	O
+into	O
+the	O
+Global	O
+Hazards	O
+of	O
+Travel	O
+(	O
+WRIGHT	O
+study	O
+)	O
+.	O
+
+For	O
+those	O
+who	O
+have	O
+an	O
+increased	O
+risk	O
+,	O
+such	O
+as	O
+oral	O
+contraceptive	O
+users	O
+and	O
+individuals	O
+with	O
+factor	O
+V	O
+Leiden	O
+,	O
+prevention	O
+may	O
+be	O
+warranted	O
+.	O
+
+Prevention	O
+may	O
+vary	O
+from	O
+simple	O
+measures	O
+,	O
+such	O
+as	O
+exercises	O
+during	O
+the	O
+flight	O
+,	O
+to	O
+measures	O
+that	O
+carry	O
+a	O
+risk	O
+themselves	O
+,	O
+such	O
+as	O
+anticoagulants	O
+.	O
+
+Specific	O
+studies	O
+are	O
+needed	O
+to	O
+assess	O
+the	O
+efficacy	O
+of	O
+these	O
+measures	O
+and	O
+their	O
+risk	O
+-	O
+benefit	O
+ratio	O
+.	O
+
+It	O
+can	O
+be	O
+concluded	O
+that	O
+the	O
+risk	O
+of	O
+venous	O
+thrombosis	O
+is	O
+2	O
+-	O
+fold	O
+increased	O
+for	O
+all	O
+travelers	O
+and	O
+to	O
+the	O
+same	O
+extent	O
+for	O
+all	O
+modes	O
+of	O
+travel	O
+.	O
+
+In	O
+individuals	O
+who	O
+use	O
+oral	O
+contraceptives	O
+,	O
+are	O
+carriers	O
+of	O
+the	O
+factor	O
+V	O
+Leiden	O
+mutation	O
+,	O
+or	O
+are	O
+particularly	O
+tall	O
+,	O
+short	O
+,	O
+or	O
+obese	O
+,	O
+this	O
+risk	O
+is	O
+considerably	O
+higher	O
+,	O
+to	O
+such	O
+an	O
+extent	O
+that	O
+studies	O
+into	O
+the	O
+efficacy	O
+of	O
+prophylactic	O
+measures	O
+are	O
+required	O
+.	O
+
+Supporting	O
+Information	O
+
+The	O
+role	O
+of	O
+the	O
+muscarinic	O
+system	O
+in	O
+regulating	O
+estradiol	O
+secretion	O
+varies	O
+during	O
+the	O
+estrous	O
+cycle	O
+:	O
+the	O
+hemiovariectomized	O
+rat	B
+model	O
+
+Abstract	O
+
+There	O
+is	O
+evidence	O
+that	O
+one	O
+gonad	O
+has	O
+functional	O
+predominance	O
+.	O
+
+The	O
+present	O
+study	O
+analyzed	O
+the	O
+acute	O
+effects	O
+of	O
+unilateral	O
+ovariectomy	O
+(	O
+ULO	O
+)	O
+and	O
+blocking	O
+the	O
+cholinergic	O
+system	O
+,	O
+by	O
+injecting	O
+atropine	O
+sulfate	O
+(	O
+ATR	O
+)	O
+,	O
+on	O
+estradiol	O
+(	O
+E2	O
+)	O
+serum	O
+concentrations	O
+during	O
+the	O
+estrous	O
+cycle	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+ULO	O
+effects	O
+on	O
+E2	O
+concentrations	O
+are	O
+asymmetric	O
+,	O
+vary	O
+during	O
+the	O
+estrous	O
+cycle	O
+,	O
+and	O
+partially	O
+depend	O
+on	O
+the	O
+cholinergic	O
+innervation	O
+.	O
+
+Background	O
+
+Estradiol	O
+secretion	O
+is	O
+regulated	O
+by	O
+pituitary	O
+[	O
+follicle	O
+stimulating	O
+hormone	O
+(	O
+FSH	O
+)	O
+and	O
+luteinizing	O
+hormones	O
+(	O
+LH	O
+)	O
+,	O
+prolactin	O
+,	O
+and	O
+adrenocorticotropin	O
+(	O
+ACTH	O
+)	O
+]	O
+.	O
+
+The	O
+effects	O
+of	O
+these	O
+hormones	O
+are	O
+modulated	O
+by	O
+neurotransmitters	O
+released	O
+by	O
+the	O
+intrinsic	O
+ovarian	O
+innervation	O
+near	O
+the	O
+follicular	O
+wall	O
+.	O
+
+Acetylcholine	O
+produced	O
+by	O
+the	O
+follicle	O
+may	O
+be	O
+one	O
+of	O
+the	O
+neurotransmitters	O
+participating	O
+in	O
+modulating	O
+the	O
+effects	O
+of	O
+pituitary	O
+hormones	O
+on	O
+the	O
+follicle	O
+[	O
+1	O
+-	O
+3	O
+]	O
+.	O
+
+Evidence	O
+suggesting	O
+that	O
+one	O
+gonad	O
+has	O
+functional	O
+predominance	O
+in	O
+mammals	O
+and	O
+birds	O
+have	O
+been	O
+published	O
+[	O
+1	O
+,	O
+4	O
+-	O
+8	O
+]	O
+.	O
+
+In	O
+previous	O
+studies	O
+we	O
+have	O
+shown	O
+that	O
+unilateral	O
+ovariectomy	O
+(	O
+ULO	O
+)	O
+modifies	O
+progesterone	O
+and	O
+/	O
+or	O
+testosterone	O
+serum	O
+concentrations	O
+,	O
+and	O
+that	O
+the	O
+effects	O
+of	O
+ULO	O
+depend	O
+on	O
+both	O
+,	O
+the	O
+stage	O
+of	O
+the	O
+estrous	O
+cycle	O
+when	O
+ULO	O
+was	O
+performed	O
+and	O
+the	O
+ovary	O
+(	O
+left	O
+or	O
+right	O
+)	O
+remaining	O
+in	O
+situ	O
+[	O
+9	O
+-	O
+11	O
+]	O
+.	O
+
+Asymmetry	O
+in	O
+ovarian	O
+functions	O
+has	O
+been	O
+explained	O
+by	O
+differences	O
+in	O
+the	O
+ovarian	O
+innervation	O
+participating	O
+in	O
+modulating	O
+the	O
+effects	O
+of	O
+gonadotropin	O
+on	O
+the	O
+ovarian	O
+follicles	O
+[	O
+1	O
+,	O
+6	O
+]	O
+.	O
+
+Kawakami	O
+et	O
+al	O
+[	O
+12	O
+]	O
+showed	O
+that	O
+electrical	O
+stimulation	O
+of	O
+the	O
+medial	O
+basal	O
+pre	O
+-	O
+chiasmatic	O
+area	O
+,	O
+the	O
+ventro	O
+-	O
+medial	O
+hypothalamus	O
+,	O
+and	O
+the	O
+areas	O
+in	O
+the	O
+mesencephalon	O
+of	O
+hypophysectomized	O
+and	O
+adrenalectomized	O
+female	O
+rats	B
+resulted	O
+in	O
+a	O
+significant	O
+increase	O
+of	O
+estradiol	O
+(	O
+E2	O
+)	O
+and	O
+progesterone	O
+(	O
+P4	O
+)	O
+plasma	O
+concentrations	O
+in	O
+the	O
+contra	O
+-	O
+lateral	O
+ovarian	O
+venous	O
+blood	O
+.	O
+
+In	O
+turn	O
+,	O
+stimulating	O
+the	O
+dorsal	O
+hippocampus	O
+,	O
+the	O
+lateral	O
+amygdala	O
+,	O
+and	O
+the	O
+mesencephalic	O
+areas	O
+resulted	O
+in	O
+lower	O
+E2	O
+and	O
+P4	O
+concentrations	O
+.	O
+
+Ovarian	O
+denervation	O
+of	O
+rats	B
+in	O
+proestrus	O
+stage	O
+blocks	O
+E2	O
+secretion	O
+induced	O
+by	O
+stimulating	O
+the	O
+medial	O
+basal	O
+pre	O
+-	O
+chiasmatic	O
+area	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+electrochemical	O
+stimulation	O
+in	O
+proestrus	O
+day	O
+of	O
+the	O
+medial	O
+basal	O
+pre	O
+-	O
+chiasmatic	O
+area	O
+of	O
+untreated	O
+rats	B
+increased	O
+E2	O
+and	O
+P4	O
+concentrations	O
+in	O
+serum	O
+.	O
+
+This	O
+effect	O
+was	O
+not	O
+observed	O
+when	O
+stimulation	O
+was	O
+applied	O
+to	O
+the	O
+pre	O
+-	O
+optic	O
+supra	O
+-	O
+chiasmatic	O
+area	O
+.	O
+
+According	O
+to	O
+the	O
+authors	O
+'	O
+interpretation	O
+of	O
+the	O
+results	O
+,	O
+the	O
+efferent	O
+neural	O
+system	O
+connecting	O
+the	O
+brain	O
+and	O
+the	O
+ovaries	O
+is	O
+supplementary	O
+to	O
+the	O
+brain	O
+-	O
+pituitary	O
+-	O
+ovarian	O
+hormonal	O
+mechanisms	O
+regulating	O
+ovarian	O
+steroid	O
+secretion	O
+,	O
+and	O
+the	O
+system	O
+may	O
+be	O
+required	O
+for	O
+adjusting	O
+ovarian	O
+responsiveness	O
+and	O
+sensitivity	O
+to	O
+gonadotropins	O
+[	O
+12	O
+,	O
+13	O
+]	O
+.	O
+
+Gerendai	O
+et	O
+al	O
+.	O
+
+[	O
+14	O
+]	O
+described	O
+a	O
+multi	O
+-	O
+synaptic	O
+neural	O
+pathway	O
+between	O
+the	O
+central	O
+nervous	O
+system	O
+and	O
+the	O
+ovaries	O
+,	O
+with	O
+the	O
+vagus	O
+nerve	O
+being	O
+one	O
+of	O
+the	O
+main	O
+neural	O
+pathways	O
+.	O
+
+In	O
+ULO	O
+treated	O
+rats	B
+,	O
+bi	O
+-	O
+lateral	O
+sectioning	O
+the	O
+vagus	O
+nerve	O
+(	O
+ventral	O
+or	O
+dorsal	O
+)	O
+results	O
+in	O
+lower	O
+compensatory	O
+ovarian	O
+hypertrophy	O
+.	O
+
+The	O
+effects	O
+of	O
+sectioning	O
+the	O
+left	O
+vagus	O
+nerve	O
+depend	O
+on	O
+the	O
+remaining	O
+ovary	O
+in	O
+situ	O
+:	O
+rats	B
+with	O
+the	O
+left	O
+ovary	O
+in	O
+situ	O
+had	O
+a	O
+larger	O
+proportion	O
+of	O
+ovulating	O
+animals	O
+,	O
+compensatory	O
+ovarian	O
+hypertrophy	O
+and	O
+number	O
+of	O
+ova	O
+shed	O
+.	O
+
+In	O
+turn	O
+,	O
+rats	B
+with	O
+the	O
+right	O
+ovary	O
+in	O
+situ	O
+showed	O
+a	O
+decrease	O
+in	O
+all	O
+parameters	O
+studied	O
+[	O
+15	O
+]	O
+.	O
+
+Based	O
+on	O
+available	O
+information	O
+,	O
+the	O
+present	O
+study	O
+aims	O
+to	O
+analyze	O
+if	O
+changes	O
+in	O
+E2	O
+secretion	O
+by	O
+the	O
+left	O
+and	O
+right	O
+ovaries	O
+vary	O
+during	O
+the	O
+estrous	O
+cycle	O
+,	O
+using	O
+the	O
+unilateral	O
+ovariectomized	O
+animal	O
+as	O
+a	O
+model	O
+of	O
+study	O
+.	O
+
+We	O
+also	O
+investigated	O
+if	O
+,	O
+throughout	O
+estrous	O
+cycle	O
+diestrus	O
+1	O
+(	O
+D1	O
+)	O
+,	O
+diestrus	O
+2	O
+(	O
+D2	O
+)	O
+and	O
+proestrus	O
+(	O
+P	O
+)	O
+,	O
+the	O
+cholinergic	O
+system	O
+modulates	O
+E2	O
+secretion	O
+in	O
+an	O
+asymmetric	O
+way	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+we	O
+analyzed	O
+the	O
+effects	O
+of	O
+injecting	O
+ATR	O
+at	O
+13	O
+.	O
+00	O
+h	O
+to	O
+rats	B
+on	O
+D1	O
+,	O
+D2	O
+or	O
+P	O
+with	O
+or	O
+without	O
+unilateral	O
+or	O
+bilateral	O
+ovariectomy	O
+.	O
+
+Materials	O
+and	O
+methods	O
+
+The	O
+study	O
+was	O
+performed	O
+with	O
+virgin	O
+adult	O
+female	O
+rats	B
+(	O
+195	O
+-	O
+225	O
+-	O
+g	O
+body	O
+weight	O
+)	O
+of	O
+the	O
+CIIZ	O
+-	O
+V	O
+strain	O
+from	O
+our	O
+own	O
+stock	O
+.	O
+
+Animals	O
+were	O
+kept	O
+under	O
+controlled	O
+lighting	O
+conditions	O
+(	O
+lights	O
+on	O
+from	O
+05	O
+:	O
+00	O
+to	O
+19	O
+:	O
+00	O
+h	O
+)	O
+,	O
+with	O
+free	O
+access	O
+to	O
+food	O
+(	O
+Purina	O
+S	O
+.	O
+A	O
+.	O
+,	O
+Mexico	O
+)	O
+and	O
+tap	O
+water	O
+;	O
+following	O
+NIH	O
+Guide	O
+parameters	O
+for	O
+the	O
+care	O
+of	O
+laboratory	O
+animals	O
+.	O
+
+The	O
+Committee	O
+of	O
+the	O
+Facultad	O
+de	O
+Estudios	O
+Superiores	O
+Zaragoza	O
+approved	O
+the	O
+experimental	O
+protocols	O
+.	O
+
+Estrous	O
+cycles	O
+were	O
+monitored	O
+by	O
+daily	O
+vaginal	O
+smears	O
+.	O
+
+Only	O
+rats	B
+showing	O
+at	O
+least	O
+two	O
+consecutive	O
+4	O
+-	O
+day	O
+cycles	O
+were	O
+used	O
+in	O
+the	O
+experiment	O
+.	O
+
+All	O
+surgeries	O
+were	O
+performed	O
+under	O
+ether	O
+anesthesia	O
+,	O
+between	O
+13	O
+:	O
+00	O
+-	O
+13	O
+:	O
+15	O
+hours	O
+.	O
+
+Rats	B
+were	O
+sacrificed	O
+by	O
+decapitation	O
+one	O
+hour	O
+after	O
+treatment	O
+.	O
+
+Experimental	O
+groups	O
+
+Rats	B
+were	O
+randomly	O
+allotted	O
+to	O
+one	O
+of	O
+the	O
+experimental	O
+groups	O
+described	O
+below	O
+.	O
+
+Animals	O
+from	O
+different	O
+experimental	O
+groups	O
+were	O
+treated	O
+simultaneously	O
+and	O
+sacrificed	O
+one	O
+hour	O
+after	O
+surgery	O
+.	O
+
+The	O
+number	O
+of	O
+animals	O
+used	O
+in	O
+each	O
+experimental	O
+group	O
+is	O
+presented	O
+in	O
+Tables	O
+1	O
+,	O
+2	O
+and	O
+3	O
+.	O
+
+Control	O
+group	O
+(	O
+N	O
+=	O
+48	O
+)	O
+.	O
+
+Non	O
+-	O
+treated	O
+cyclic	O
+rats	B
+sacrificed	O
+at	O
+14	O
+:	O
+00	O
+h	O
+on	O
+D1	O
+(	O
+17	O
+rats	B
+)	O
+,	O
+D2	O
+(	O
+19	O
+rats	B
+)	O
+and	O
+P	O
+(	O
+12	O
+rats	B
+)	O
+.	O
+
+Ether	O
+anesthesia	O
+(	O
+N	O
+=	O
+24	O
+)	O
+:	O
+Groups	O
+of	O
+rats	B
+,	O
+on	O
+specific	O
+stages	O
+(	O
+D1	O
+,	O
+D2	O
+or	O
+P	O
+)	O
+of	O
+the	O
+estrous	O
+cycle	O
+,	O
+were	O
+anesthetized	O
+for	O
+10	O
+min	O
+and	O
+sacrificed	O
+one	O
+hour	O
+later	O
+.	O
+
+Unilateral	O
+peritoneal	O
+perforation	O
+(	O
+sham	O
+operation	O
+)	O
+(	O
+N	O
+=	O
+53	O
+)	O
+:	O
+A	O
+unilateral	O
+incision	O
+was	O
+performed	O
+2	O
+-	O
+cm	O
+below	O
+the	O
+last	O
+rib	O
+;	O
+affecting	O
+skin	O
+,	O
+muscle	O
+,	O
+and	O
+peritoneum	O
+.	O
+
+The	O
+ovaries	O
+were	O
+not	O
+injured	O
+or	O
+manipulated	O
+.	O
+
+After	O
+surgical	O
+procedures	O
+the	O
+wound	O
+was	O
+sealed	O
+.	O
+
+Bilateral	O
+peritoneal	O
+perforation	O
+(	O
+sham	O
+operation	O
+2	O
+)	O
+(	O
+N	O
+=	O
+27	O
+)	O
+.	O
+
+A	O
+bilateral	O
+incision	O
+below	O
+the	O
+last	O
+rib	O
+,	O
+including	O
+skin	O
+and	O
+muscle	O
+,	O
+was	O
+performed	O
+.	O
+
+The	O
+ovaries	O
+were	O
+not	O
+injured	O
+or	O
+manipulated	O
+.	O
+
+After	O
+surgical	O
+procedures	O
+the	O
+wound	O
+was	O
+sealed	O
+.	O
+
+Unilateral	O
+ovariectomy	O
+(	O
+ULO	O
+)	O
+(	O
+N	O
+=	O
+50	O
+)	O
+:	O
+A	O
+unilateral	O
+incision	O
+below	O
+the	O
+last	O
+rib	O
+,	O
+including	O
+skin	O
+and	O
+muscle	O
+was	O
+performed	O
+,	O
+and	O
+the	O
+right	O
+or	O
+left	O
+ovary	O
+was	O
+extirpated	O
+.	O
+
+The	O
+wound	O
+was	O
+subsequently	O
+sealed	O
+.	O
+
+Bilateral	O
+ovariectomy	O
+(	O
+N	O
+=	O
+23	O
+)	O
+:	O
+A	O
+bilateral	O
+incision	O
+below	O
+the	O
+last	O
+rib	O
+,	O
+including	O
+skin	O
+and	O
+muscle	O
+was	O
+performed	O
+,	O
+and	O
+the	O
+ovaries	O
+removed	O
+.	O
+
+The	O
+wound	O
+was	O
+subsequently	O
+sealed	O
+.	O
+
+Blocking	O
+the	O
+cholinergic	O
+system	O
+
+To	O
+analyze	O
+the	O
+effects	O
+of	O
+blocking	O
+the	O
+cholinergic	O
+system	O
+,	O
+groups	O
+of	O
+animals	O
+were	O
+injected	O
+with	O
+atropine	O
+sulfate	O
+(	O
+ATR	O
+,	O
+Sigma	O
+Chem	O
+.	O
+Co	O
+.	O
+St	O
+.	O
+Louis	O
+,	O
+Mo	O
+.	O
+)	O
+.	O
+
+ATR	O
+was	O
+injected	O
+one	O
+hour	O
+before	O
+surgery	O
+at	O
+doses	O
+known	O
+to	O
+block	O
+ovulation	O
+:	O
+in	O
+D1	O
+,	O
+100	O
+mg	O
+/	O
+kg	O
+body	O
+weight	O
+(	O
+b	O
+.	O
+w	O
+.	O
+)	O
+;	O
+in	O
+D2	O
+,	O
+300	O
+mg	O
+/	O
+kg	O
+b	O
+.	O
+w	O
+.	O
+;	O
+and	O
+in	O
+P	O
+,	O
+700	O
+mg	O
+/	O
+kg	O
+b	O
+.	O
+w	O
+.	O
+
+[	O
+16	O
+]	O
+.	O
+
+One	O
+hour	O
+after	O
+ATR	O
+treatment	O
+,	O
+rats	B
+were	O
+randomly	O
+allotted	O
+to	O
+one	O
+of	O
+the	O
+following	O
+treatments	O
+:	O
+unilateral	O
+peritoneal	O
+perforation	O
+,	O
+bilateral	O
+peritoneal	O
+perforation	O
+,	O
+ULO	O
+,	O
+or	O
+bilateral	O
+ovariectomy	O
+.	O
+
+All	O
+animals	O
+were	O
+sacrificed	O
+one	O
+hour	O
+after	O
+surgery	O
+.	O
+
+For	O
+control	O
+purposes	O
+,	O
+untreated	O
+rats	B
+,	O
+on	O
+D1	O
+,	O
+D2	O
+or	O
+P	O
+,	O
+were	O
+injected	O
+with	O
+ATR	O
+in	O
+the	O
+same	O
+dose	O
+as	O
+in	O
+their	O
+corresponding	O
+treatment	O
+group	O
+.	O
+
+The	O
+animals	O
+were	O
+sacrificed	O
+two	O
+hours	O
+after	O
+treatment	O
+.	O
+
+Autopsy	O
+procedures	O
+
+Animals	O
+were	O
+sacrificed	O
+by	O
+decapitation	O
+.	O
+
+The	O
+blood	O
+of	O
+the	O
+trunk	O
+was	O
+collected	O
+in	O
+a	O
+test	O
+tube	O
+,	O
+allowed	O
+to	O
+clot	O
+at	O
+room	O
+temperature	O
+for	O
+30	O
+minutes	O
+and	O
+centrifuged	O
+at	O
+3	O
+,	O
+000	O
+rpm	O
+for	O
+15	O
+minutes	O
+.	O
+
+Serum	O
+was	O
+stored	O
+at	O
+-	O
+20	O
+degrees	O
+C	O
+,	O
+until	O
+E2	O
+concentrations	O
+were	O
+measured	O
+.	O
+
+Hormone	O
+assay	O
+
+Concentrations	O
+of	O
+E2	O
+in	O
+serum	O
+were	O
+measured	O
+by	O
+Radio	O
+-	O
+Immuno	O
+-	O
+Assay	O
+(	O
+RIA	O
+)	O
+;	O
+using	O
+kits	O
+purchased	O
+from	O
+Diagnostic	O
+Products	O
+(	O
+Los	O
+Angeles	O
+,	O
+CA	O
+)	O
+.	O
+
+Results	O
+are	O
+expressed	O
+in	O
+pg	O
+/	O
+ml	O
+.	O
+
+The	O
+Intra	O
+-	O
+and	O
+inter	O
+-	O
+assay	O
+variation	O
+coefficients	O
+were	O
+6	O
+.	O
+9	O
+%	O
+and	O
+10	O
+.	O
+8	O
+%	O
+,	O
+respectively	O
+.	O
+
+Statistics	O
+
+Data	O
+on	O
+hormonal	O
+concentrations	O
+in	O
+serum	O
+were	O
+analyzed	O
+using	O
+multivariate	O
+analysis	O
+of	O
+variance	O
+(	O
+MANOVA	O
+)	O
+followed	O
+by	O
+Tukey	O
+'	O
+s	O
+test	O
+.	O
+
+Differences	O
+in	O
+serum	O
+hormone	O
+concentrations	O
+between	O
+two	O
+groups	O
+were	O
+analyzed	O
+by	O
+Student	O
+'	O
+s	O
+t	O
+-	O
+test	O
+.	O
+
+A	O
+probability	O
+value	O
+of	O
+less	O
+than	O
+5	O
+%	O
+was	O
+considered	O
+significant	O
+.	O
+
+Results	O
+
+Effects	O
+of	O
+ether	O
+anesthesia	O
+and	O
+unilateral	O
+or	O
+bilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+
+In	O
+the	O
+control	O
+group	O
+,	O
+animals	O
+sacrificed	O
+on	O
+P	O
+showed	O
+significantly	O
+higher	O
+E2	O
+serum	O
+concentration	O
+than	O
+animals	O
+sacrificed	O
+on	O
+D1	O
+or	O
+D2	O
+(	O
+D1	O
+:	O
+55	O
+.	O
+3	O
++	O
+/	O
+-	O
+8	O
+.	O
+0	O
+;	O
+D2	O
+:	O
+59	O
+.	O
+1	O
++	O
+/	O
+-	O
+7	O
+.	O
+9	O
+;	O
+P	O
+:	O
+158	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+8	O
+)	O
+.	O
+
+Compared	O
+to	O
+the	O
+control	O
+group	O
+,	O
+ether	O
+anesthesia	O
+treatment	O
+did	O
+not	O
+modify	O
+E2	O
+serum	O
+concentrations	O
+(	O
+D1	O
+:	O
+62	O
+.	O
+9	O
++	O
+/	O
+-	O
+8	O
+.	O
+4	O
+;	O
+D2	O
+:	O
+69	O
+.	O
+5	O
++	O
+/	O
+-	O
+12	O
+.	O
+0	O
+;	O
+P	O
+:	O
+164	O
+.	O
+1	O
++	O
+/	O
+-	O
+17	O
+.	O
+6	O
+)	O
+.	O
+
+Since	O
+ether	O
+anesthesia	O
+did	O
+not	O
+modify	O
+E2	O
+serum	O
+concentrations	O
+,	O
+treatment	O
+results	O
+are	O
+compared	O
+to	O
+their	O
+respective	O
+control	O
+group	O
+.	O
+
+The	O
+effects	O
+on	O
+E2	O
+serum	O
+concentrations	O
+of	O
+unilaterally	O
+or	O
+bilaterally	O
+perforating	O
+the	O
+peritoneum	O
+depended	O
+on	O
+the	O
+side	O
+of	O
+the	O
+peritoneum	O
+and	O
+the	O
+stage	O
+of	O
+the	O
+estrous	O
+cycle	O
+when	O
+perforation	O
+surgery	O
+was	O
+performed	O
+.	O
+
+Perforating	O
+the	O
+left	O
+peritoneum	O
+on	O
+D1	O
+resulted	O
+in	O
+lower	O
+E2	O
+serum	O
+concentrations	O
+(	O
+55	O
+%	O
+)	O
+,	O
+while	O
+bilateral	O
+perforation	O
+,	O
+or	O
+perforating	O
+the	O
+right	O
+side	O
+of	O
+the	O
+peritoneum	O
+,	O
+had	O
+no	O
+apparent	O
+effects	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Perforating	O
+the	O
+right	O
+side	O
+of	O
+the	O
+peritoneum	O
+on	O
+D2	O
+day	O
+resulted	O
+in	O
+E2	O
+concentration	O
+increases	O
+(	O
+184	O
+%	O
+)	O
+,	O
+while	O
+perforating	O
+the	O
+left	O
+side	O
+resulted	O
+in	O
+a	O
+decrease	O
+(	O
+51	O
+%	O
+)	O
+of	O
+E2	O
+serum	O
+concentrations	O
+.	O
+
+Bilateral	O
+perforation	O
+had	O
+no	O
+apparent	O
+effects	O
+on	O
+hormone	O
+concentrations	O
+.	O
+
+Perforating	O
+the	O
+peritoneum	O
+on	O
+P	O
+phase	O
+(	O
+left	O
+,	O
+right	O
+or	O
+bilateral	O
+)	O
+resulted	O
+in	O
+hormone	O
+serum	O
+concentration	O
+decreases	O
+(	O
+Left	O
+30	O
+%	O
+;	O
+Right	O
+50	O
+%	O
+;	O
+Bilateral	O
+41	O
+%	O
+)	O
+.	O
+
+Results	O
+are	O
+summarized	O
+in	O
+Table	O
+1	O
+.	O
+
+Effects	O
+of	O
+unilateral	O
+or	O
+bilateral	O
+ovariectomy	O
+
+When	O
+surgery	O
+was	O
+performed	O
+on	O
+D1	O
+,	O
+no	O
+significant	O
+differences	O
+in	O
+E2	O
+serum	O
+concentrations	O
+were	O
+observed	O
+between	O
+rats	B
+with	O
+ULO	O
+(	O
+animals	O
+with	O
+intact	O
+left	O
+or	O
+right	O
+ovary	O
+in	O
+situ	O
+)	O
+or	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Animals	O
+with	O
+the	O
+left	O
+intact	O
+ovary	O
+in	O
+situ	O
+showed	O
+significantly	O
+higher	O
+E2	O
+serum	O
+concentrations	O
+than	O
+animals	O
+with	O
+the	O
+right	O
+intact	O
+ovary	O
+in	O
+situ	O
+(	O
+61	O
+.	O
+5	O
++	O
+/	O
+-	O
+9	O
+.	O
+4	O
+vs	O
+.	O
+17	O
+.	O
+3	O
++	O
+/	O
+-	O
+4	O
+.	O
+3	O
+,	O
+p	O
+<	O
+0	O
+.	O
+05	O
+Student	O
+'	O
+s	O
+t	O
+test	O
+)	O
+.	O
+
+Compared	O
+to	O
+animals	O
+with	O
+unilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+,	O
+animals	O
+with	O
+right	O
+ULO	O
+(	O
+left	O
+ovary	O
+in	O
+situ	O
+)	O
+performed	O
+on	O
+D2	O
+had	O
+lower	O
+E2	O
+serum	O
+concentrations	O
+(	O
+55	O
+%	O
+)	O
+.	O
+
+Such	O
+differences	O
+were	O
+not	O
+observed	O
+in	O
+rats	B
+with	O
+left	O
+ULO	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+As	O
+in	O
+rats	B
+treated	O
+on	O
+D1	O
+,	O
+E2	O
+serum	O
+concentrations	O
+were	O
+significantly	O
+higher	O
+in	O
+animals	O
+treated	O
+on	O
+D2	O
+with	O
+the	O
+left	O
+ovary	O
+in	O
+situ	O
+(	O
+right	O
+ULO	O
+)	O
+than	O
+in	O
+animals	O
+with	O
+the	O
+right	O
+ovary	O
+in	O
+situ	O
+(	O
+49	O
+.	O
+5	O
++	O
+/	O
+-	O
+10	O
+.	O
+8	O
+vs	O
+.	O
+26	O
+.	O
+0	O
++	O
+/	O
+-	O
+6	O
+.	O
+9	O
+)	O
+.	O
+
+In	O
+animals	O
+treated	O
+on	O
+P	O
+,	O
+right	O
+ULO	O
+(	O
+left	O
+ovary	O
+in	O
+situ	O
+)	O
+resulted	O
+in	O
+higher	O
+E2	O
+(	O
+180	O
+%	O
+)	O
+serum	O
+concentrations	O
+than	O
+in	O
+animals	O
+with	O
+unilateral	O
+peritoneum	O
+perforation	O
+.	O
+
+ULO	O
+performed	O
+on	O
+the	O
+left	O
+side	O
+(	O
+right	O
+ovary	O
+in	O
+situ	O
+)	O
+,	O
+resulted	O
+in	O
+significantly	O
+lower	O
+(	O
+45	O
+%	O
+)	O
+E2	O
+serum	O
+concentrations	O
+compared	O
+to	O
+rats	B
+with	O
+a	O
+unilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+As	O
+observed	O
+in	O
+rats	B
+treated	O
+on	O
+D1	O
+or	O
+D2	O
+,	O
+when	O
+the	O
+intact	O
+left	O
+ovary	O
+remains	O
+in	O
+situ	O
+,	O
+estradiol	O
+serum	O
+concentrations	O
+were	O
+significantly	O
+higher	O
+than	O
+in	O
+animals	O
+with	O
+the	O
+intact	O
+right	O
+ovary	O
+in	O
+situ	O
+(	O
+142	O
+.	O
+0	O
++	O
+/	O
+-	O
+14	O
+.	O
+1	O
+vs	O
+.	O
+61	O
+.	O
+5	O
++	O
+/	O
+-	O
+6	O
+.	O
+0	O
+)	O
+.	O
+
+Compared	O
+to	O
+animals	O
+with	O
+a	O
+bilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+,	O
+bilateral	O
+ovariectomy	O
+resulted	O
+in	O
+significantly	O
+lower	O
+E2	O
+serum	O
+concentrations	O
+,	O
+regardless	O
+of	O
+the	O
+stage	O
+of	O
+the	O
+estrous	O
+cycle	O
+surgery	O
+performed	O
+(	O
+D1	O
+74	O
+%	O
+;	O
+D2	O
+73	O
+%	O
+;	O
+P	O
+84	O
+%	O
+)	O
+.	O
+
+Results	O
+are	O
+summarized	O
+in	O
+Table	O
+2	O
+.	O
+
+Effects	O
+of	O
+blocking	O
+the	O
+cholinergic	O
+system	O
+
+Injecting	O
+ATR	O
+on	O
+D1	O
+or	O
+P	O
+resulted	O
+in	O
+E2	O
+serum	O
+concentrations	O
+decreases	O
+(	O
+84	O
+%	O
+and	O
+67	O
+%	O
+,	O
+respectively	O
+)	O
+,	O
+and	O
+had	O
+no	O
+apparent	O
+effects	O
+on	O
+E2	O
+serum	O
+concentrations	O
+when	O
+injected	O
+on	O
+D2	O
+(	O
+Table	O
+3	O
+)	O
+.	O
+
+Figure	O
+2	O
+shows	O
+that	O
+the	O
+effects	O
+of	O
+blocking	O
+the	O
+cholinergic	O
+system	O
+of	O
+rats	B
+with	O
+unilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+depended	O
+on	O
+both	O
+,	O
+the	O
+side	O
+(	O
+left	O
+or	O
+right	O
+)	O
+and	O
+the	O
+phase	O
+of	O
+the	O
+estrous	O
+when	O
+surgery	O
+was	O
+performed	O
+.	O
+
+Injecting	O
+ATR	O
+on	O
+D1	O
+or	O
+D2	O
+resulted	O
+in	O
+a	O
+significant	O
+drop	O
+in	O
+E2	O
+serum	O
+concentrations	O
+in	O
+animals	O
+with	O
+sham	O
+treatment	O
+on	O
+the	O
+right	O
+side	O
+.	O
+
+Blocking	O
+the	O
+cholinergic	O
+system	O
+of	O
+rats	B
+with	O
+left	O
+side	O
+peritoneum	O
+perforation	O
+on	O
+D1	O
+or	O
+P	O
+resulted	O
+in	O
+a	O
+drop	O
+in	O
+E2	O
+serum	O
+concentrations	O
+(	O
+52	O
+%	O
+;	O
+47	O
+%	O
+,	O
+respectively	O
+)	O
+,	O
+while	O
+the	O
+same	O
+treatment	O
+performed	O
+on	O
+D2	O
+resulted	O
+in	O
+a	O
+significant	O
+E2	O
+concentrations	O
+increase	O
+(	O
+157	O
+%	O
+)	O
+.	O
+
+Figure	O
+3	O
+shows	O
+the	O
+effects	O
+of	O
+blocking	O
+the	O
+cholinergic	O
+system	O
+of	O
+rats	B
+with	O
+ULO	O
+.	O
+
+ATR	O
+treatment	O
+on	O
+D1	O
+or	O
+P	O
+stages	O
+performed	O
+on	O
+rats	B
+with	O
+the	O
+left	O
+ovary	O
+in	O
+situ	O
+resulted	O
+in	O
+a	O
+significant	O
+drop	O
+of	O
+E2	O
+serum	O
+concentrations	O
+(	O
+65	O
+%	O
+;	O
+62	O
+%	O
+respectively	O
+)	O
+.	O
+
+Such	O
+effects	O
+were	O
+not	O
+observed	O
+in	O
+rats	B
+treated	O
+on	O
+D2	O
+.	O
+
+When	O
+ATR	O
+treatment	O
+was	O
+performed	O
+on	O
+rats	B
+with	O
+the	O
+right	O
+ovary	O
+in	O
+situ	O
+on	O
+D1	O
+,	O
+E2	O
+serum	O
+concentrations	O
+were	O
+lower	O
+(	O
+48	O
+%	O
+)	O
+than	O
+in	O
+ULO	O
+animals	O
+.	O
+
+Blocking	O
+the	O
+cholinergic	O
+system	O
+on	O
+D2	O
+resulted	O
+in	O
+E2	O
+serum	O
+concentrations	O
+increase	O
+(	O
+159	O
+%	O
+)	O
+.	O
+
+When	O
+the	O
+treatment	O
+was	O
+performed	O
+on	O
+P	O
+,	O
+no	O
+significant	O
+differences	O
+in	O
+E2	O
+serum	O
+concentrations	O
+were	O
+observed	O
+.	O
+
+Compared	O
+to	O
+bilateral	O
+treatment	O
+,	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+or	O
+bilateral	O
+ovariectomy	O
+,	O
+ATR	O
+treatment	O
+on	O
+D1	O
+resulted	O
+in	O
+significant	O
+E2	O
+serum	O
+concentrations	O
+decreases	O
+,	O
+90	O
+%	O
+in	O
+bilateral	O
+peritoneal	O
+perforation	O
+and	O
+60	O
+%	O
+in	O
+bilateral	O
+ovariectomized	O
+animals	O
+.	O
+
+Blocking	O
+the	O
+cholinergic	O
+system	O
+on	O
+D2	O
+,	O
+to	O
+rats	B
+with	O
+bilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+or	O
+bilateral	O
+ovariectomy	O
+resulted	O
+in	O
+E2	O
+serum	O
+concentrations	O
+increases	O
+(	O
+159	O
+%	O
+and	O
+253	O
+%	O
+respectively	O
+)	O
+,	O
+while	O
+injecting	O
+ATR	O
+to	O
+animals	O
+treated	O
+on	O
+P	O
+had	O
+no	O
+apparent	O
+effects	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+Discussion	O
+
+The	O
+results	O
+obtained	O
+in	O
+the	O
+present	O
+study	O
+suggest	O
+that	O
+the	O
+ability	O
+to	O
+compensate	O
+the	O
+secretion	O
+of	O
+E2	O
+by	O
+the	O
+missing	O
+ovary	O
+is	O
+different	O
+between	O
+the	O
+right	O
+and	O
+left	O
+ovaries	O
+and	O
+varies	O
+during	O
+the	O
+estrous	O
+cycle	O
+.	O
+
+Similarly	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+the	O
+cholinergic	O
+system	O
+participates	O
+in	O
+regulating	O
+E2	O
+secretion	O
+by	O
+the	O
+ovary	O
+,	O
+and	O
+that	O
+such	O
+participation	O
+varies	O
+depending	O
+on	O
+the	O
+ovary	O
+remaining	O
+in	O
+situ	O
+and	O
+the	O
+stage	O
+of	O
+the	O
+estrous	O
+cycle	O
+when	O
+the	O
+surgical	O
+procedure	O
+was	O
+performed	O
+.	O
+
+Previously	O
+,	O
+we	O
+suggested	O
+the	O
+existence	O
+of	O
+a	O
+neural	O
+pathway	O
+arising	O
+from	O
+the	O
+peritoneum	O
+that	O
+participates	O
+in	O
+regulating	O
+E2	O
+[	O
+9	O
+]	O
+,	O
+P4	O
+[	O
+10	O
+]	O
+and	O
+testosterone	O
+secretion	O
+[	O
+11	O
+]	O
+.	O
+
+In	O
+the	O
+rat	B
+,	O
+the	O
+sensory	O
+information	O
+arising	O
+from	O
+the	O
+peritoneum	O
+is	O
+sent	O
+to	O
+the	O
+nucleus	O
+tractus	O
+solitarius	O
+and	O
+stimulates	O
+neurokinine	O
+-	O
+B	O
+receptors	O
+[	O
+17	O
+]	O
+.	O
+
+Since	O
+perforating	O
+the	O
+peritoneum	O
+unilaterally	O
+on	O
+each	O
+day	O
+of	O
+the	O
+estrous	O
+cycle	O
+changed	O
+E2	O
+serum	O
+concentrations	O
+,	O
+we	O
+think	O
+that	O
+each	O
+side	O
+of	O
+the	O
+peritoneum	O
+sends	O
+different	O
+neural	O
+information	O
+through	O
+the	O
+superior	O
+ovarian	O
+nerve	O
+(	O
+SON	O
+)	O
+to	O
+the	O
+ovary	O
+and	O
+the	O
+central	O
+nervous	O
+system	O
+,	O
+perhaps	O
+reaching	O
+nuclei	O
+related	O
+to	O
+the	O
+vagus	O
+nerve	O
+.	O
+
+A	O
+study	O
+analyzing	O
+the	O
+distribution	O
+of	O
+sensory	O
+neurons	O
+innervating	O
+the	O
+peritoneum	O
+showed	O
+that	O
+when	O
+tracer	O
+was	O
+placed	O
+on	O
+the	O
+area	O
+where	O
+the	O
+peritoneum	O
+covers	O
+the	O
+abdominal	O
+wall	O
+,	O
+labeled	O
+neurons	O
+were	O
+observed	O
+only	O
+in	O
+the	O
+ipsilateral	O
+dorsal	O
+root	O
+ganglia	O
+[	O
+18	O
+]	O
+.	O
+
+The	O
+authors	O
+suggest	O
+that	O
+most	O
+of	O
+the	O
+parietal	O
+peritoneum	O
+receives	O
+sensory	O
+nerves	O
+from	O
+dorsal	O
+root	O
+ganglia	O
+,	O
+and	O
+visceral	O
+peritoneum	O
+from	O
+both	O
+,	O
+the	O
+spinal	O
+and	O
+vagus	O
+nerves	O
+.	O
+
+According	O
+to	O
+Stener	O
+-	O
+Victorin	O
+et	O
+al	O
+.	O
+
+(	O
+19	O
+)	O
+repeated	O
+electro	O
+-	O
+acupunture	O
+treatments	O
+in	O
+rats	B
+with	O
+polycystic	O
+ovary	O
+syndrome	O
+(	O
+PCO	O
+)	O
+,	O
+induced	O
+by	O
+a	O
+single	O
+injection	O
+of	O
+estradiol	O
+valerate	O
+,	O
+resulted	O
+in	O
+lower	O
+nerve	O
+growth	O
+factor	O
+(	O
+NGF	O
+)	O
+concentrations	O
+at	O
+the	O
+ovarian	O
+level	O
+than	O
+in	O
+non	O
+-	O
+electro	O
+-	O
+acupunture	O
+treated	O
+PCO	O
+rats	B
+.	O
+
+In	O
+our	O
+experiments	O
+,	O
+perforating	O
+the	O
+peritoneum	O
+affected	O
+the	O
+same	O
+somatic	O
+segments	O
+employed	O
+by	O
+Stener	O
+-	O
+Victorin	O
+et	O
+.	O
+
+al	O
+.	O
+
+[	O
+19	O
+]	O
+.	O
+
+We	O
+presume	O
+that	O
+peritoneum	O
+surgery	O
+resulted	O
+in	O
+an	O
+increase	O
+of	O
+NGF	O
+concentrations	O
+at	O
+the	O
+ovarian	O
+level	O
+,	O
+which	O
+in	O
+turn	O
+induced	O
+hyper	O
+-	O
+androgenism	O
+,	O
+as	O
+observed	O
+in	O
+women	O
+with	O
+PCO	O
+[	O
+20	O
+]	O
+.	O
+
+Previously	O
+,	O
+we	O
+showed	O
+that	O
+the	O
+unilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+results	O
+in	O
+a	O
+significant	O
+increase	O
+in	O
+testosterone	O
+serum	O
+concentrations	O
+[	O
+11	O
+]	O
+.	O
+
+Because	O
+E2	O
+serum	O
+concentrations	O
+did	O
+not	O
+increase	O
+after	O
+left	O
+or	O
+bilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+,	O
+we	O
+suppose	O
+that	O
+the	O
+neural	O
+information	O
+originating	O
+from	O
+the	O
+peritoneum	O
+inhibits	O
+the	O
+mechanisms	O
+regulating	O
+aromatase	O
+activity	O
+within	O
+the	O
+follicle	O
+.	O
+
+One	O
+of	O
+the	O
+ovaries	O
+'	O
+sources	O
+of	O
+catecholamines	O
+arrives	O
+through	O
+the	O
+SON	O
+.	O
+
+In	O
+the	O
+ovary	O
+,	O
+the	O
+SON	O
+fibers	O
+are	O
+mainly	O
+distributed	O
+in	O
+the	O
+peri	O
+-	O
+follicular	O
+theca	O
+layer	O
+,	O
+and	O
+in	O
+close	O
+relation	O
+with	O
+the	O
+cells	O
+of	O
+the	O
+theca	O
+interna	O
+[	O
+21	O
+,	O
+22	O
+]	O
+.	O
+
+Sectioning	O
+the	O
+SON	O
+of	O
+rats	B
+in	O
+P	O
+results	O
+in	O
+a	O
+sudden	O
+drop	O
+of	O
+P4	O
+and	O
+E2	O
+concentrations	O
+in	O
+the	O
+ovarian	O
+vein	O
+effluent	O
+[	O
+23	O
+]	O
+,	O
+while	O
+the	O
+same	O
+procedure	O
+on	O
+estrus	O
+did	O
+not	O
+modify	O
+E2	O
+concentrations	O
+[	O
+24	O
+]	O
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+perforating	O
+the	O
+peritoneum	O
+modifies	O
+the	O
+type	O
+and	O
+/	O
+or	O
+rate	O
+of	O
+information	O
+arriving	O
+to	O
+the	O
+ovary	O
+via	O
+the	O
+SON	O
+.	O
+
+Another	O
+possibility	O
+is	O
+that	O
+perforating	O
+the	O
+left	O
+side	O
+of	O
+the	O
+peritoneum	O
+results	O
+in	O
+an	O
+increase	O
+release	O
+of	O
+ovarian	O
+gamma	O
+amino	O
+butyric	O
+acid	O
+(	O
+GABA	O
+)	O
+,	O
+and	O
+a	O
+subsequent	O
+increase	O
+of	O
+E2	O
+concentrations	O
+.	O
+
+According	O
+to	O
+Erd	O
+o	O
+,	O
+et	O
+.	O
+
+al	O
+.	O
+
+[	O
+25	O
+]	O
+and	O
+Laszlo	O
+,	O
+et	O
+.	O
+
+al	O
+.	O
+
+[	O
+26	O
+]	O
+,	O
+injecting	O
+GABA	O
+into	O
+pseudo	O
+-	O
+pregnant	O
+rats	B
+increases	O
+E2	O
+concentration	O
+in	O
+the	O
+blood	O
+.	O
+
+Present	O
+results	O
+indicate	O
+that	O
+injecting	O
+ATR	O
+,	O
+before	O
+unilateral	O
+or	O
+bilateral	O
+perforation	O
+of	O
+the	O
+peritoneum	O
+,	O
+to	O
+rats	B
+in	O
+D1	O
+or	O
+P	O
+,	O
+results	O
+in	O
+lower	O
+E2serum	O
+concentrations	O
+;	O
+leading	O
+us	O
+to	O
+think	O
+that	O
+some	O
+of	O
+the	O
+neural	O
+fibers	O
+present	O
+in	O
+the	O
+peritoneum	O
+are	O
+muscarinic	O
+.	O
+
+It	O
+is	O
+also	O
+possible	O
+that	O
+blocking	O
+the	O
+cholinergic	O
+innervation	O
+,	O
+by	O
+ATR	O
+treatment	O
+,	O
+results	O
+in	O
+lower	O
+adrenaline	O
+and	O
+norepinephrine	O
+release	O
+by	O
+the	O
+adrenal	O
+medulla	O
+.	O
+
+Our	O
+results	O
+,	O
+and	O
+those	O
+of	O
+others	O
+,	O
+suggest	O
+that	O
+stimulating	O
+on	O
+D2	O
+the	O
+sensory	O
+receptors	O
+located	O
+on	O
+the	O
+left	O
+side	O
+of	O
+the	O
+peritoneum	O
+triggers	O
+an	O
+E2	O
+secretion	O
+inhibitory	O
+mechanism	O
+,	O
+that	O
+the	O
+sensory	O
+pathway	O
+arising	O
+from	O
+the	O
+right	O
+side	O
+has	O
+a	O
+stimulatory	O
+effect	O
+,	O
+and	O
+that	O
+both	O
+are	O
+mediated	O
+by	O
+the	O
+cholinergic	O
+muscarinic	O
+system	O
+.	O
+
+Previously	O
+,	O
+we	O
+showed	O
+that	O
+injecting	O
+ATR	O
+to	O
+rats	B
+in	O
+D2	O
+results	O
+in	O
+increases	O
+of	O
+P4	O
+serum	O
+concentrations	O
+originating	O
+from	O
+the	O
+adrenals	O
+[	O
+8	O
+]	O
+,	O
+without	O
+having	O
+apparent	O
+effects	O
+on	O
+testosterone	O
+serum	O
+concentrations	O
+[	O
+11	O
+]	O
+.	O
+
+Since	O
+P4	O
+and	O
+androgens	O
+are	O
+precursors	O
+in	O
+the	O
+synthesis	O
+of	O
+E2	O
+,	O
+we	O
+presume	O
+that	O
+this	O
+mechanism	O
+may	O
+explain	O
+the	O
+increase	O
+in	O
+E2	O
+serum	O
+concentrations	O
+observed	O
+in	O
+rats	B
+with	O
+peritoneum	O
+perforation	O
+previously	O
+injected	O
+with	O
+ATR	O
+.	O
+
+Another	O
+possibility	O
+explaining	O
+the	O
+differences	O
+on	O
+E2	O
+secretion	O
+regulation	O
+during	O
+the	O
+estrous	O
+cycle	O
+is	O
+that	O
+the	O
+effects	O
+of	O
+the	O
+cholinergic	O
+system	O
+take	O
+place	O
+through	O
+changes	O
+at	O
+the	O
+celiac	O
+ganglion	O
+level	O
+.	O
+
+According	O
+to	O
+Aguado	O
+and	O
+Ojeda	O
+[	O
+23	O
+]	O
+,	O
+acetylcholine	O
+inhibits	O
+P4	O
+secretion	O
+in	O
+the	O
+celiac	O
+ganglion	O
+-	O
+SON	O
+-	O
+ovary	O
+preparation	O
+obtained	O
+from	O
+rats	B
+in	O
+D1	O
+or	O
+D2	O
+,	O
+while	O
+the	O
+preparation	O
+obtained	O
+from	O
+rats	B
+in	O
+P	O
+resulted	O
+in	O
+only	O
+a	O
+moderate	O
+stimulation	O
+.	O
+
+Since	O
+there	O
+is	O
+evidence	O
+that	O
+fibers	O
+from	O
+the	O
+vagus	O
+nerve	O
+innervate	O
+neurons	O
+in	O
+the	O
+celiac	O
+ganglion	O
+[	O
+27	O
+]	O
+,	O
+we	O
+presume	O
+that	O
+the	O
+cholinergic	O
+system	O
+modulates	O
+the	O
+sympathetic	O
+post	O
+-	O
+ganglionar	O
+activity	O
+and	O
+the	O
+secretory	O
+ability	O
+of	O
+the	O
+ovaries	O
+through	O
+the	O
+SON	O
+.	O
+
+Conclusion	O
+
+Based	O
+on	O
+the	O
+differences	O
+in	O
+E2	O
+serum	O
+concentrations	O
+in	O
+rats	B
+with	O
+ULO	O
+,	O
+present	O
+results	O
+suggest	O
+that	O
+the	O
+capacity	O
+to	O
+release	O
+E2	O
+by	O
+the	O
+left	O
+and	O
+right	O
+ovaries	O
+varies	O
+during	O
+the	O
+estrous	O
+cycle	O
+.	O
+
+We	O
+presume	O
+that	O
+the	O
+left	O
+ovary	O
+releases	O
+more	O
+E2	O
+than	O
+the	O
+right	O
+one	O
+.	O
+
+As	O
+previously	O
+proposed	O
+,	O
+another	O
+possibility	O
+is	O
+that	O
+neural	O
+communication	O
+between	O
+the	O
+ovaries	O
+modulates	O
+E2	O
+secretion	O
+.	O
+
+Case	O
+report	O
+:	O
+rapidly	O
+fatal	O
+bowel	O
+ischaemia	O
+on	O
+clozapine	O
+treatment	O
+
+Abstract	O
+
+Background	O
+
+There	O
+have	O
+been	O
+previous	O
+reported	O
+deaths	O
+due	O
+to	O
+clozapine	O
+-	O
+induced	O
+constipation	O
+.	O
+
+In	O
+all	O
+these	O
+cases	O
+patients	B
+have	O
+experienced	O
+prior	O
+abdominal	O
+symptoms	O
+over	O
+a	O
+period	O
+of	O
+weeks	O
+or	O
+months	O
+.	O
+
+Case	O
+presentation	O
+
+We	O
+report	O
+the	O
+sudden	O
+death	O
+due	O
+to	O
+constipation	O
+of	O
+a	O
+healthy	O
+young	O
+male	O
+patient	B
+on	O
+clozapine	O
+without	O
+any	O
+known	O
+history	O
+of	O
+prior	O
+abdominal	O
+symptoms	O
+.	O
+
+Conclusion	O
+
+Psychiatrists	O
+need	O
+to	O
+be	O
+alert	O
+to	O
+the	O
+medical	O
+emergencies	O
+which	O
+can	O
+occur	O
+in	O
+the	O
+context	O
+of	O
+clozapine	O
+treatment	O
+and	O
+also	O
+need	O
+to	O
+make	O
+other	O
+clinicians	O
+who	O
+may	O
+have	O
+contact	O
+with	O
+their	O
+patients	B
+aware	O
+of	O
+these	O
+.	O
+
+Background	O
+
+There	O
+have	O
+been	O
+six	O
+previously	O
+published	O
+cases	O
+of	O
+death	O
+secondary	O
+to	O
+clozapine	O
+-	O
+induced	O
+constipation	O
+[	O
+1	O
+-	O
+3	O
+]	O
+.	O
+
+Of	O
+these	O
+,	O
+two	O
+patients	B
+died	O
+from	O
+faecal	O
+peritonitis	O
+,	O
+two	O
+from	O
+aspiration	O
+of	O
+faeculent	O
+vomitus	O
+as	O
+a	O
+result	O
+of	O
+bowel	O
+obstruction	O
+and	O
+two	O
+from	O
+bowel	O
+necrosis	O
+.	O
+
+In	O
+all	O
+these	O
+cases	O
+there	O
+had	O
+been	O
+prior	O
+complaints	O
+of	O
+constipation	O
+and	O
+/	O
+or	O
+other	O
+abdominal	O
+symptoms	O
+for	O
+weeks	O
+to	O
+months	O
+before	O
+the	O
+fatal	O
+event	O
+.	O
+
+Here	O
+we	O
+describe	O
+a	O
+case	O
+of	O
+constipation	O
+,	O
+presumably	O
+clozapine	O
+-	O
+induced	O
+,	O
+where	O
+death	O
+from	O
+bowel	O
+ischaemia	O
+occured	O
+within	O
+2	O
+days	O
+from	O
+the	O
+first	O
+complaint	O
+of	O
+constipation	O
+and	O
+without	O
+any	O
+prior	O
+reported	O
+abdominal	O
+symptoms	O
+which	O
+might	O
+have	O
+provided	O
+a	O
+warning	O
+to	O
+the	O
+clinicians	O
+involved	O
+.	O
+
+Case	O
+presentation	O
+
+A	O
+20	O
+-	O
+year	O
+-	O
+old	O
+male	O
+with	O
+a	O
+year	O
+long	O
+history	O
+of	O
+schizophrenia	O
+which	O
+had	O
+been	O
+unresponsive	O
+to	O
+trials	O
+of	O
+two	O
+atypical	O
+antipsychotic	O
+drugs	O
+was	O
+commenced	O
+on	O
+clozapine	O
+.	O
+
+The	O
+dose	O
+was	O
+titrated	O
+over	O
+the	O
+next	O
+year	O
+to	O
+900	O
+mg	O
+daily	O
+.	O
+
+Due	O
+to	O
+persisting	O
+negative	O
+symptoms	O
+amisulpiride	O
+400	O
+mg	O
+twice	O
+daily	O
+was	O
+added	O
+with	O
+good	O
+response	O
+after	O
+one	O
+month	O
+.	O
+
+The	O
+patient	B
+was	O
+reviewed	O
+regularly	O
+over	O
+the	O
+next	O
+year	O
+,	O
+continued	O
+to	O
+improve	O
+and	O
+did	O
+not	O
+report	O
+any	O
+side	O
+effects	O
+to	O
+members	O
+of	O
+the	O
+multidisciplinary	O
+mental	O
+health	O
+team	O
+working	O
+to	O
+support	O
+him	O
+in	O
+the	O
+community	O
+.	O
+
+He	O
+appeared	O
+to	O
+be	O
+fit	O
+and	O
+healthy	O
+.	O
+
+Although	O
+he	O
+usually	O
+lived	O
+in	O
+supported	O
+accommodation	O
+he	O
+was	O
+staying	O
+temporarily	O
+with	O
+his	O
+family	O
+and	O
+from	O
+their	O
+account	O
+he	O
+complained	O
+of	O
+having	O
+constipation	O
+for	O
+2	O
+days	O
+before	O
+presenting	O
+to	O
+his	O
+GP	O
+with	O
+severe	O
+abdominal	O
+pain	O
+.	O
+
+He	O
+was	O
+prescribed	O
+medication	O
+and	O
+returned	O
+home	O
+but	O
+his	O
+condition	O
+deteriorated	O
+further	O
+and	O
+a	O
+few	O
+hours	O
+later	O
+an	O
+ambulance	O
+was	O
+called	O
+.	O
+
+He	O
+collapsed	O
+and	O
+died	O
+before	O
+reaching	O
+hospital	O
+.	O
+
+Post	O
+mortem	O
+examination	O
+revealed	O
+that	O
+he	O
+had	O
+impacted	O
+faeces	O
+which	O
+had	O
+pressed	O
+against	O
+the	O
+bowel	O
+wall	O
+causing	O
+ischaemia	O
+.	O
+
+This	O
+had	O
+led	O
+to	O
+infarction	O
+of	O
+this	O
+part	O
+of	O
+the	O
+bowel	O
+.	O
+
+Conclusion	O
+
+This	O
+case	O
+demonstrates	O
+that	O
+death	O
+can	O
+occur	O
+over	O
+a	O
+very	O
+short	O
+time	O
+course	O
+from	O
+constipation	O
+,	O
+in	O
+this	O
+case	O
+presumably	O
+induced	O
+by	O
+clozapine	O
+.	O
+
+Death	O
+from	O
+constipation	O
+and	O
+subsequent	O
+bowel	O
+infarction	O
+is	O
+relatively	O
+common	O
+in	O
+elderly	O
+patients	B
+and	O
+infarction	O
+causes	O
+a	O
+far	O
+more	O
+rapid	O
+and	O
+dangerous	O
+deterioration	O
+than	O
+does	O
+intestinal	O
+obstruction	O
+.	O
+
+In	O
+the	O
+present	O
+case	O
+this	O
+meant	O
+that	O
+this	O
+patient	B
+did	O
+not	O
+have	O
+any	O
+contact	O
+with	O
+psychiatric	O
+services	O
+between	O
+the	O
+onset	O
+of	O
+his	O
+symptoms	O
+and	O
+his	O
+rapid	O
+demise	O
+,	O
+in	O
+spite	O
+of	O
+regular	O
+follow	O
+-	O
+up	O
+.	O
+
+Although	O
+the	O
+risk	O
+of	O
+neutropenia	O
+is	O
+relatively	O
+well	O
+-	O
+known	O
+,	O
+it	O
+should	O
+be	O
+borne	O
+in	O
+mind	O
+that	O
+clozapine	O
+is	O
+reported	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+number	O
+of	O
+other	O
+syndromes	O
+which	O
+may	O
+be	O
+rapidly	O
+fatal	O
+including	O
+not	O
+only	O
+constipation	O
+and	O
+obstruction	O
+but	O
+also	O
+cardiovascular	O
+collapse	O
+,	O
+seizures	O
+and	O
+ketoacidosis	O
+.	O
+
+Psychiatrists	O
+working	O
+with	O
+such	O
+patients	B
+should	O
+not	O
+only	O
+themselves	O
+be	O
+vigilant	O
+regarding	O
+such	O
+complications	O
+but	O
+should	O
+take	O
+steps	O
+to	O
+see	O
+that	O
+other	O
+clinicians	O
+to	O
+whom	O
+the	O
+patient	B
+may	O
+present	O
+are	O
+also	O
+aware	O
+of	O
+them	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+Both	O
+authors	O
+were	O
+equally	O
+involved	O
+in	O
+the	O
+preparation	O
+of	O
+this	O
+manuscript	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+A	O
+disease	O
+-	O
+specific	O
+measure	O
+of	O
+health	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+for	O
+use	O
+in	O
+adults	O
+with	O
+immune	O
+thrombocytopenic	O
+purpura	O
+:	O
+Its	O
+development	O
+and	O
+validation	O
+
+Abstract	O
+
+Background	O
+
+No	O
+validated	O
+disease	O
+-	O
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+are	O
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+to	O
+assess	O
+health	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+(	O
+HRQoL	O
+)	O
+in	O
+adult	O
+subjects	O
+with	O
+immune	O
+thrombocytopenic	O
+purpura	O
+(	O
+ITP	O
+)	O
+.	O
+
+Therefore	O
+,	O
+we	O
+sought	O
+to	O
+develop	O
+and	O
+validate	O
+the	O
+ITP	O
+-	O
+Patient	B
+Assessment	O
+Questionnaire	O
+(	O
+ITP	O
+-	O
+PAQ	O
+)	O
+for	O
+adult	O
+subjects	O
+with	O
+ITP	O
+.	O
+
+Methods	O
+
+Information	O
+from	O
+literature	O
+reviews	O
+,	O
+focus	O
+groups	O
+with	O
+subjects	O
+,	O
+and	O
+clinicians	O
+were	O
+used	O
+to	O
+develop	O
+50	O
+ITP	O
+-	O
+PAQ	O
+items	O
+.	O
+
+Factor	O
+analyses	O
+were	O
+conducted	O
+to	O
+develop	O
+the	O
+scale	O
+structure	O
+and	O
+reduce	O
+the	O
+number	O
+of	O
+items	O
+.	O
+
+The	O
+final	O
+44	O
+-	O
+item	O
+ITP	O
+-	O
+PAQ	O
+,	O
+which	O
+includes	O
+ten	O
+scales	O
+[	O
+Symptoms	O
+(	O
+S	O
+)	O
+,	O
+Bother	O
+-	O
+Physical	O
+Health	O
+(	O
+B	O
+)	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+(	O
+FT	O
+)	O
+,	O
+Activity	O
+(	O
+A	O
+)	O
+,	O
+Fear	O
+(	O
+FR	O
+)	O
+,	O
+Psychological	O
+Health	O
+(	O
+PH	O
+)	O
+,	O
+Work	O
+(	O
+W	O
+)	O
+,	O
+Social	O
+Activity	O
+(	O
+SA	O
+)	O
+,	O
+Women	B
+'	O
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+Reproductive	O
+Health	O
+(	O
+RH	O
+)	O
+,	O
+and	O
+Overall	O
+(	O
+QoL	O
+)	O
+]	O
+,	O
+was	O
+self	O
+-	O
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+to	O
+adult	O
+ITP	O
+subjects	O
+at	O
+baseline	O
+and	O
+7	O
+-	O
+10	O
+days	O
+later	O
+.	O
+
+Test	O
+-	O
+retest	O
+reliability	O
+,	O
+internal	O
+consistency	O
+reliability	O
+,	O
+construct	O
+and	O
+known	O
+groups	O
+validity	O
+of	O
+the	O
+final	O
+ITP	O
+-	O
+PAQ	O
+were	O
+evaluated	O
+.	O
+
+Results	O
+
+Seventy	O
+-	O
+three	O
+subjects	O
+with	O
+ITP	O
+completed	O
+the	O
+questionnaire	O
+twice	O
+.	O
+
+Test	O
+-	O
+retest	O
+reliability	O
+,	O
+as	O
+measured	O
+by	O
+the	O
+intra	O
+-	O
+class	O
+correlation	O
+,	O
+ranged	O
+from	O
+0	O
+.	O
+52	O
+-	O
+0	O
+.	O
+90	O
+.	O
+
+Internal	O
+consistency	O
+reliability	O
+was	O
+demonstrated	O
+with	O
+Cronbach	O
+'	O
+s	O
+alpha	O
+for	O
+all	O
+scales	O
+above	O
+the	O
+acceptable	O
+level	O
+of	O
+0	O
+.	O
+70	O
+(	O
+range	O
+:	O
+0	O
+.	O
+71	O
+-	O
+0	O
+.	O
+92	O
+)	O
+,	O
+except	O
+for	O
+RH	O
+(	O
+0	O
+.	O
+66	O
+)	O
+.	O
+
+Construct	O
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+,	O
+assessed	O
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+correlating	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+with	O
+established	O
+measures	O
+(	O
+Short	O
+Form	O
+-	O
+36	O
+v	O
+.	O
+1	O
+,	O
+SF	O
+-	O
+36	O
+and	O
+Center	O
+for	O
+Epidemiologic	O
+Studies	O
+Depression	O
+Scale	O
+,	O
+CES	O
+-	O
+D	O
+)	O
+,	O
+was	O
+demonstrated	O
+through	O
+moderate	O
+correlations	O
+between	O
+the	O
+ITP	O
+-	O
+PAQ	O
+SA	O
+and	O
+SF	O
+-	O
+36	O
+Social	O
+Function	O
+scales	O
+(	O
+r	O
+=	O
+0	O
+.	O
+67	O
+)	O
+,	O
+and	O
+between	O
+ITP	O
+-	O
+PAQ	O
+PH	O
+and	O
+SF	O
+-	O
+36	O
+Mental	O
+Health	O
+Scales	O
+(	O
+r	O
+=	O
+0	O
+.	O
+63	O
+)	O
+.	O
+
+Moderate	O
+to	O
+strong	O
+inter	O
+-	O
+scale	O
+correlations	O
+were	O
+reported	O
+between	O
+ITP	O
+-	O
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+CES	O
+-	O
+D	O
+,	O
+except	O
+for	O
+the	O
+RH	O
+scale	O
+.	O
+
+Known	O
+groups	O
+validity	O
+was	O
+evaluated	O
+by	O
+comparing	O
+mean	O
+scores	O
+for	O
+groups	O
+that	O
+differed	O
+clinically	O
+.	O
+
+Statistically	O
+significant	O
+differences	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+were	O
+observed	O
+when	O
+subjects	O
+were	O
+categorized	O
+by	O
+treatment	O
+status	O
+[	O
+S	O
+,	O
+FT	O
+,	O
+B	O
+,	O
+A	O
+,	O
+PH	O
+,	O
+and	O
+QoL	O
+,	O
+perceived	O
+effectiveness	O
+of	O
+ITP	O
+treatment	O
+[	O
+S	O
+]	O
+,	O
+and	O
+time	O
+elapsed	O
+since	O
+ITP	O
+diagnosis	O
+[	O
+PH	O
+]	O
+.	O
+
+Conclusion	O
+
+Results	O
+provide	O
+preliminary	O
+evidence	O
+of	O
+the	O
+reliability	O
+and	O
+validity	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+in	O
+adult	O
+subjects	O
+with	O
+ITP	O
+.	O
+
+Further	O
+work	O
+should	O
+be	O
+conducted	O
+to	O
+assess	O
+the	O
+responsiveness	O
+and	O
+to	O
+estimate	O
+the	O
+minimal	O
+clinical	O
+important	O
+difference	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+to	O
+more	O
+fully	O
+understand	O
+the	O
+impact	O
+of	O
+ITP	O
+and	O
+its	O
+treatments	O
+on	O
+HRQoL	O
+.	O
+
+Background	O
+
+Immune	O
+thrombocytopenic	O
+purpura	O
+(	O
+ITP	O
+)	O
+is	O
+a	O
+disorder	O
+characterized	O
+by	O
+autoimmune	O
+-	O
+mediated	O
+platelet	O
+destruction	O
+and	O
+suboptimal	O
+platelet	O
+production	O
+[	O
+1	O
+-	O
+3	O
+]	O
+that	O
+results	O
+in	O
+a	O
+decrease	O
+in	O
+the	O
+number	O
+of	O
+circulating	O
+platelets	O
+and	O
+increases	O
+the	O
+risk	O
+of	O
+bleeding	O
+events	O
+.	O
+
+The	O
+estimated	O
+prevalence	O
+rate	O
+for	O
+ITP	O
+in	O
+the	O
+United	O
+States	O
+is	O
+9	O
+.	O
+5	O
+/	O
+100	O
+,	O
+000	O
+[	O
+4	O
+]	O
+.	O
+
+Adult	O
+women	B
+are	O
+disproportionately	O
+affected	O
+by	O
+the	O
+disorder	O
+,	O
+with	O
+a	O
+female	O
+to	O
+male	O
+ratio	O
+of	O
+nearly	O
+two	O
+to	O
+one	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+disorder	O
+rarely	O
+remits	O
+spontaneously	O
+in	O
+adult	O
+subjects	O
+[	O
+1	O
+]	O
+.	O
+
+The	O
+mortality	O
+rate	O
+is	O
+relatively	O
+low	O
+(	O
+<	O
+1	O
+%	O
+)	O
+[	O
+6	O
+]	O
+in	O
+adults	O
+less	O
+than	O
+65	O
+years	O
+of	O
+age	O
+.	O
+
+Morbidity	O
+increases	O
+above	O
+age	O
+65	O
+,	O
+primarily	O
+as	O
+a	O
+result	O
+of	O
+an	O
+increase	O
+in	O
+age	O
+-	O
+related	O
+major	O
+bleeding	O
+events	O
+[	O
+7	O
+]	O
+.	O
+
+Initial	O
+therapy	O
+for	O
+ITP	O
+consists	O
+of	O
+some	O
+combination	O
+of	O
+glucocorticoids	O
+,	O
+intravenous	O
+immune	O
+globulin	O
+(	O
+IVIg	O
+)	O
+or	O
+anti	O
+-	O
+D	O
+[	O
+8	O
+]	O
+.	O
+
+Splenectomy	O
+is	O
+often	O
+considered	O
+if	O
+these	O
+therapies	O
+fail	O
+.	O
+
+Approximately	O
+two	O
+-	O
+thirds	O
+of	O
+patients	B
+treated	O
+with	O
+splenectomy	O
+achieve	O
+a	O
+sustained	O
+remission	O
+[	O
+1	O
+,	O
+5	O
+,	O
+9	O
+]	O
+.	O
+
+Patients	B
+who	O
+fail	O
+splenectomy	O
+are	O
+treated	O
+with	O
+a	O
+wide	O
+variety	O
+of	O
+agents	O
+including	O
+corticosteroids	O
+,	O
+danazol	O
+,	O
+and	O
+chemotherapeutic	O
+agents	O
+.	O
+
+Morbidity	O
+and	O
+mortality	O
+in	O
+these	O
+refractory	O
+patients	B
+are	O
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+[	O
+1	O
+,	O
+6	O
+,	O
+8	O
+]	O
+.	O
+
+Patient	B
+-	O
+reported	O
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+(	O
+PRO	O
+)	O
+,	O
+including	O
+health	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+(	O
+HRQoL	O
+)	O
+measures	O
+,	O
+are	O
+critical	O
+components	O
+for	O
+evaluating	O
+and	O
+understanding	O
+treatment	O
+effects	O
+from	O
+the	O
+subject	O
+'	O
+s	O
+perspective	O
+.	O
+
+The	O
+Food	O
+and	O
+Drug	O
+Administration	O
+(	O
+FDA	O
+)	O
+indicates	O
+that	O
+PRO	O
+measures	O
+are	O
+important	O
+to	O
+assess	O
+because	O
+they	O
+may	O
+:	O
+1	O
+)	O
+detect	O
+treatment	O
+effects	O
+known	O
+only	O
+to	O
+the	O
+subject	O
+;	O
+2	O
+)	O
+understand	O
+the	O
+subject	O
+'	O
+s	O
+perspective	O
+regarding	O
+treatment	O
+effect	O
+;	O
+or	O
+3	O
+)	O
+provide	O
+information	O
+not	O
+included	O
+in	O
+a	O
+clinician	O
+'	O
+s	O
+subject	O
+notes	O
+[	O
+10	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+Committee	O
+for	O
+Medicinal	O
+Products	O
+for	O
+Human	B
+Use	O
+of	O
+the	O
+European	O
+Medicines	O
+Agency	O
+defines	O
+HRQoL	O
+as	O
+"	O
+the	O
+subject	O
+'	O
+s	O
+subjective	O
+perception	O
+of	O
+the	O
+impact	O
+of	O
+his	O
+disease	O
+and	O
+its	O
+treatment	O
+(	O
+s	O
+)	O
+on	O
+his	O
+daily	O
+life	O
+,	O
+physical	O
+,	O
+psychological	O
+and	O
+social	O
+functioning	O
+and	O
+well	O
+-	O
+being	O
+"	O
+[	O
+11	O
+]	O
+.	O
+
+Currently	O
+,	O
+limited	O
+data	O
+are	O
+available	O
+on	O
+the	O
+assessment	O
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+the	O
+impact	O
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+symptoms	O
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+adult	O
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+.	O
+
+Symptoms	O
+of	O
+ITP	O
+,	O
+such	O
+as	O
+spontaneous	O
+bruising	O
+,	O
+menorrhagia	O
+,	O
+mucosal	O
+bleeding	O
+and	O
+prolonged	O
+bleeding	O
+with	O
+injury	O
+,	O
+may	O
+significantly	O
+affect	O
+HRQoL	O
+in	O
+ITP	O
+subjects	O
+[	O
+12	O
+]	O
+.	O
+
+Treatments	O
+for	O
+chronic	O
+ITP	O
+can	O
+also	O
+be	O
+associated	O
+with	O
+substantial	O
+side	O
+effects	O
+[	O
+5	O
+,	O
+8	O
+]	O
+.	O
+
+In	O
+addition	O
+,	O
+subjects	O
+who	O
+are	O
+resistant	O
+to	O
+current	O
+therapies	O
+are	O
+likely	O
+to	O
+experience	O
+an	O
+even	O
+greater	O
+decrement	O
+to	O
+their	O
+HRQoL	O
+than	O
+responders	O
+to	O
+treatment	O
+.	O
+
+Thus	O
+,	O
+restoring	O
+and	O
+/	O
+or	O
+maintaining	O
+quality	O
+of	O
+life	O
+should	O
+be	O
+an	O
+important	O
+goal	O
+of	O
+treatment	O
+.	O
+
+While	O
+the	O
+primary	O
+markers	O
+for	O
+ITP	O
+include	O
+hematologic	O
+measures	O
+such	O
+as	O
+platelet	O
+counts	O
+,	O
+clinical	O
+measures	O
+typically	O
+do	O
+not	O
+assess	O
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+subject	O
+'	O
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+and	O
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+-	O
+being	O
+.	O
+
+Therefore	O
+,	O
+subjects	O
+and	O
+physicians	O
+may	O
+want	O
+to	O
+weigh	O
+the	O
+impact	O
+of	O
+ITP	O
+therapies	O
+on	O
+HRQoL	O
+endpoints	O
+when	O
+making	O
+treatment	O
+decisions	O
+.	O
+
+Previously	O
+,	O
+no	O
+validated	O
+disease	O
+-	O
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+measures	O
+were	O
+available	O
+to	O
+evaluate	O
+quality	O
+of	O
+life	O
+in	O
+adult	O
+ITP	O
+subjects	O
+;	O
+however	O
+,	O
+two	O
+disease	O
+-	O
+specific	O
+HRQoL	O
+questionnaires	O
+have	O
+been	O
+developed	O
+for	O
+use	O
+in	O
+children	B
+with	O
+ITP	O
+[	O
+13	O
+,	O
+14	O
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+
+Thus	O
+,	O
+we	O
+sought	O
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+develop	O
+a	O
+questionnaire	O
+that	O
+would	O
+be	O
+appropriate	O
+to	O
+assess	O
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+impact	O
+of	O
+ITP	O
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+its	O
+treatments	O
+on	O
+HRQoL	O
+in	O
+adult	O
+subjects	O
+.	O
+
+The	O
+objective	O
+of	O
+this	O
+current	O
+manuscript	O
+is	O
+to	O
+describe	O
+the	O
+development	O
+and	O
+initial	O
+validation	O
+of	O
+a	O
+newly	O
+developed	O
+HRQoL	O
+questionnaire	O
+for	O
+use	O
+in	O
+adult	O
+subjects	O
+with	O
+ITP	O
+.	O
+
+Methods	O
+
+Overview	O
+
+A	O
+newly	O
+developed	O
+questionnaire	O
+,	O
+which	O
+assesses	O
+issues	O
+of	O
+importance	O
+to	O
+ITP	O
+subjects	O
+,	O
+was	O
+developed	O
+based	O
+on	O
+available	O
+published	O
+literature	O
+,	O
+existing	O
+questionnaires	O
+,	O
+expert	O
+clinical	O
+opinion	O
+,	O
+and	O
+input	O
+from	O
+subjects	O
+with	O
+ITP	O
+.	O
+
+Subjects	O
+and	O
+Procedures	O
+
+To	O
+develop	O
+the	O
+questionnaire	O
+,	O
+three	O
+focus	O
+groups	O
+with	O
+ITP	O
+subjects	O
+were	O
+conducted	O
+in	O
+geographically	O
+diverse	O
+locations	O
+(	O
+San	O
+Diego	O
+,	O
+CA	O
+,	O
+New	O
+York	O
+,	O
+NY	O
+,	O
+and	O
+Oklahoma	O
+City	O
+,	O
+OK	O
+)	O
+.	O
+
+Each	O
+of	O
+the	O
+three	O
+sites	O
+recruited	O
+a	O
+convenience	O
+sample	O
+of	O
+five	O
+to	O
+eight	O
+ITP	O
+subjects	O
+who	O
+were	O
+being	O
+treated	O
+on	O
+an	O
+outpatient	O
+basis	O
+.	O
+
+To	O
+be	O
+eligible	O
+,	O
+subjects	O
+were	O
+required	O
+to	O
+have	O
+active	O
+disease	O
+and	O
+be	O
+>	O
+=	O
+18	O
+years	O
+of	O
+age	O
+.	O
+
+Although	O
+platelet	O
+count	O
+data	O
+were	O
+not	O
+required	O
+for	O
+participation	O
+in	O
+the	O
+focus	O
+groups	O
+,	O
+clinicians	O
+at	O
+each	O
+site	O
+considered	O
+the	O
+subjects	O
+to	O
+have	O
+active	O
+disease	O
+,	O
+usually	O
+an	O
+indication	O
+that	O
+platelet	O
+levels	O
+have	O
+dropped	O
+below	O
+120	O
+x	O
+109L	O
+and	O
+the	O
+subject	O
+requires	O
+treatment	O
+and	O
+/	O
+or	O
+more	O
+frequent	O
+monitoring	O
+.	O
+
+In	O
+total	O
+,	O
+23	O
+ITP	O
+subjects	O
+participated	O
+in	O
+the	O
+focus	O
+groups	O
+after	O
+providing	O
+their	O
+informed	O
+consent	O
+.	O
+
+To	O
+validate	O
+the	O
+questionnaire	O
+,	O
+a	O
+convenience	O
+sample	O
+of	O
+subjects	O
+was	O
+recruited	O
+from	O
+the	O
+same	O
+three	O
+clinical	O
+sites	O
+in	O
+New	O
+York	O
+,	O
+NY	O
+,	O
+Oklahoma	O
+City	O
+,	O
+OK	O
+,	O
+and	O
+La	O
+Jolla	O
+,	O
+CA	O
+.	O
+
+Subjects	O
+were	O
+eligible	O
+if	O
+they	O
+were	O
+>	O
+=	O
+18	O
+years	O
+of	O
+age	O
+,	O
+had	O
+active	O
+disease	O
+,	O
+and	O
+were	O
+willing	O
+to	O
+complete	O
+a	O
+self	O
+-	O
+administered	O
+questionnaire	O
+at	O
+two	O
+time	O
+points	O
+.	O
+
+Target	O
+enrollment	O
+was	O
+roughly	O
+72	O
+subjects	O
+(	O
+24	O
+subjects	O
+from	O
+each	O
+site	O
+)	O
+.	O
+
+The	O
+study	O
+protocol	O
+was	O
+approved	O
+by	O
+a	O
+local	O
+institutional	O
+review	O
+board	O
+at	O
+each	O
+site	O
+and	O
+was	O
+carried	O
+out	O
+in	O
+accordance	O
+with	O
+Good	O
+Clinical	O
+Practice	O
+and	O
+International	O
+Conference	O
+on	O
+Harmonization	O
+guidelines	O
+and	O
+the	O
+Declaration	O
+of	O
+Helsinki	O
+.	O
+
+Written	O
+informed	O
+consent	O
+was	O
+obtained	O
+from	O
+each	O
+subject	O
+prior	O
+to	O
+enrollment	O
+.	O
+
+Creation	O
+of	O
+Questionnaire	O
+/	O
+Item	O
+Selection	O
+
+A	O
+trained	O
+moderator	O
+led	O
+all	O
+focus	O
+groups	O
+using	O
+a	O
+detailed	O
+discussion	O
+guide	O
+.	O
+
+Subjects	O
+discussed	O
+their	O
+ITP	O
+history	O
+,	O
+treatment	O
+,	O
+ITP	O
+symptoms	O
+,	O
+and	O
+the	O
+impact	O
+of	O
+ITP	O
+on	O
+daily	O
+activities	O
+.	O
+
+Each	O
+focus	O
+group	O
+lasted	O
+approximately	O
+three	O
+hours	O
+,	O
+and	O
+subjects	O
+were	O
+provided	O
+with	O
+an	O
+honorarium	O
+for	O
+their	O
+time	O
+.	O
+
+Following	O
+the	O
+focus	O
+group	O
+session	O
+,	O
+all	O
+subjects	O
+completed	O
+a	O
+questionnaire	O
+which	O
+included	O
+the	O
+SF	O
+-	O
+36	O
+v1	O
+[	O
+15	O
+]	O
+and	O
+ITP	O
+-	O
+specific	O
+questions	O
+.	O
+
+The	O
+ITP	O
+-	O
+specific	O
+items	O
+were	O
+developed	O
+based	O
+on	O
+clinical	O
+input	O
+[	O
+12	O
+,	O
+16	O
+-	O
+18	O
+]	O
+.	O
+
+The	O
+ITP	O
+-	O
+specific	O
+items	O
+assessed	O
+the	O
+impact	O
+of	O
+ITP	O
+on	O
+the	O
+subject	O
+'	O
+s	O
+overall	O
+quality	O
+of	O
+life	O
+,	O
+relationships	O
+,	O
+ability	O
+to	O
+sleep	O
+,	O
+menstruation	O
+/	O
+gynecological	O
+history	O
+,	O
+and	O
+sexual	O
+activity	O
+.	O
+
+The	O
+ITP	O
+-	O
+specific	O
+questions	O
+also	O
+assessed	O
+the	O
+subject	O
+'	O
+s	O
+response	O
+to	O
+ITP	O
+treatments	O
+and	O
+any	O
+side	O
+effects	O
+.	O
+
+Transcripts	O
+of	O
+the	O
+focus	O
+groups	O
+were	O
+summarized	O
+and	O
+reviewed	O
+by	O
+the	O
+study	O
+team	O
+.	O
+
+The	O
+initial	O
+draft	O
+of	O
+the	O
+ITP	O
+Subject	O
+Assessment	O
+Questionnaire	O
+(	O
+ITP	O
+-	O
+PAQ	O
+)	O
+was	O
+developed	O
+after	O
+reviewing	O
+information	O
+from	O
+the	O
+literature	O
+searches	O
+,	O
+existing	O
+questionnaires	O
+,	O
+expert	O
+opinion	O
+,	O
+focus	O
+group	O
+transcripts	O
+,	O
+and	O
+the	O
+questionnaire	O
+responses	O
+from	O
+the	O
+focus	O
+group	O
+subjects	O
+.	O
+
+The	O
+initial	O
+ITP	O
+-	O
+PAQ	O
+consisted	O
+of	O
+50	O
+items	O
+that	O
+assesses	O
+the	O
+impact	O
+of	O
+ITP	O
+in	O
+the	O
+areas	O
+of	O
+physical	O
+health	O
+,	O
+mental	O
+health	O
+,	O
+work	O
+,	O
+social	O
+activity	O
+,	O
+reproductive	O
+health	O
+(	O
+relevant	O
+for	O
+women	B
+only	O
+)	O
+,	O
+and	O
+overall	O
+quality	O
+of	O
+life	O
+.	O
+
+Factor	O
+analyses	O
+were	O
+conducted	O
+which	O
+yielded	O
+six	O
+unique	O
+domains	O
+.	O
+
+The	O
+impact	O
+of	O
+ITP	O
+on	O
+physical	O
+health	O
+was	O
+measured	O
+by	O
+four	O
+scales	O
+that	O
+evaluated	O
+ITP	O
+-	O
+related	O
+symptoms	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+,	O
+Bother	O
+-	O
+Physical	O
+Health	O
+,	O
+and	O
+Activity	O
+.	O
+
+Its	O
+impact	O
+on	O
+mental	O
+health	O
+was	O
+measured	O
+by	O
+two	O
+scales	O
+that	O
+evaluated	O
+psychological	O
+distress	O
+and	O
+fear	O
+.	O
+
+A	O
+copy	O
+of	O
+the	O
+questionnaire	O
+can	O
+be	O
+obtained	O
+by	O
+contacting	O
+Janet	O
+L	O
+.	O
+Nichol	O
+and	O
+sample	O
+items	O
+are	O
+included	O
+Table	O
+2	O
+.	O
+
+Statistical	O
+Analyses	O
+
+A	O
+validation	O
+study	O
+was	O
+conducted	O
+to	O
+evaluate	O
+the	O
+psychometric	O
+properties	O
+of	O
+the	O
+newly	O
+developed	O
+ITP	O
+-	O
+PAQ	O
+questionnaire	O
+so	O
+that	O
+it	O
+could	O
+be	O
+used	O
+to	O
+measure	O
+the	O
+impact	O
+of	O
+ITP	O
+in	O
+adult	O
+subjects	O
+in	O
+future	O
+studies	O
+.	O
+
+Standard	O
+psychometric	O
+methods	O
+were	O
+used	O
+to	O
+evaluate	O
+the	O
+reliability	O
+and	O
+validity	O
+of	O
+the	O
+questionnaire	O
+[	O
+19	O
+,	O
+20	O
+]	O
+.	O
+
+Eligible	O
+subjects	O
+completed	O
+the	O
+baseline	O
+questionnaire	O
+at	O
+the	O
+site	O
+or	O
+by	O
+mail	O
+after	O
+providing	O
+telephone	O
+consent	O
+.	O
+
+An	O
+informed	O
+consent	O
+form	O
+and	O
+baseline	O
+questionnaire	O
+was	O
+mailed	O
+to	O
+those	O
+subjects	O
+who	O
+gave	O
+their	O
+initial	O
+consent	O
+via	O
+telephone	O
+.	O
+
+These	O
+completed	O
+documents	O
+were	O
+returned	O
+by	O
+mail	O
+to	O
+the	O
+investigators	O
+.	O
+
+At	O
+follow	O
+up	O
+,	O
+each	O
+subject	O
+was	O
+mailed	O
+the	O
+same	O
+questionnaire	O
+and	O
+asked	O
+to	O
+complete	O
+it	O
+a	O
+second	O
+time	O
+(	O
+for	O
+evaluating	O
+test	O
+-	O
+retest	O
+reliability	O
+)	O
+approximately	O
+two	O
+weeks	O
+later	O
+.	O
+
+Additionally	O
+,	O
+subjects	O
+completed	O
+the	O
+SF	O
+-	O
+36	O
+and	O
+the	O
+CES	O
+-	O
+D	O
+[	O
+21	O
+]	O
+for	O
+validation	O
+purposes	O
+at	O
+both	O
+assessments	O
+.	O
+
+Demographic	O
+and	O
+clinical	O
+characteristics	O
+were	O
+also	O
+solicited	O
+in	O
+order	O
+to	O
+more	O
+fully	O
+describe	O
+the	O
+study	O
+population	O
+.	O
+
+Each	O
+study	O
+subject	O
+received	O
+an	O
+honorarium	O
+for	O
+completing	O
+the	O
+questionnaires	O
+.	O
+
+Scale	O
+creation	O
+and	O
+confirmatory	O
+factor	O
+analysis	O
+
+Confirmatory	O
+factor	O
+analyses	O
+were	O
+conducted	O
+to	O
+test	O
+the	O
+hypothesized	O
+structure	O
+of	O
+the	O
+scales	O
+.	O
+
+Two	O
+models	O
+using	O
+LISREL	O
+version	O
+8	O
+were	O
+tested	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+first	O
+model	O
+consisted	O
+of	O
+all	O
+50	O
+HRQoL	O
+items	O
+and	O
+10	O
+factors	O
+,	O
+whereas	O
+the	O
+second	O
+model	O
+consisted	O
+of	O
+a	O
+subset	O
+of	O
+the	O
+50	O
+-	O
+item	O
+correlation	O
+matrix	O
+.	O
+
+Only	O
+women	B
+respond	O
+to	O
+the	O
+six	O
+items	O
+comprising	O
+the	O
+Reproductive	O
+Health	O
+scale	O
+,	O
+so	O
+the	O
+items	O
+were	O
+not	O
+included	O
+in	O
+the	O
+second	O
+LISREL	O
+model	O
+to	O
+avoid	O
+estimation	O
+biases	O
+.	O
+
+The	O
+remaining	O
+44	O
+items	O
+were	O
+analyzed	O
+.	O
+
+Model	O
+fit	O
+was	O
+evaluated	O
+using	O
+the	O
+goodness	O
+-	O
+of	O
+-	O
+fit	O
+(	O
+GFI	O
+)	O
+,	O
+the	O
+normed	O
+fit	O
+index	O
+(	O
+NFI	O
+)	O
+,	O
+the	O
+non	O
+-	O
+normed	O
+fit	O
+index	O
+(	O
+NNFI	O
+)	O
+,	O
+the	O
+comparative	O
+fit	O
+index	O
+(	O
+CIF	O
+)	O
+,	O
+and	O
+the	O
+root	O
+mean	O
+square	O
+error	O
+of	O
+approximation	O
+(	O
+RMSEA	O
+)	O
+.	O
+
+For	O
+the	O
+confirmatory	O
+models	O
+,	O
+index	O
+values	O
+greater	O
+than	O
+0	O
+.	O
+95	O
+indicate	O
+better	O
+fit	O
+,	O
+and	O
+RMSEA	O
+values	O
+less	O
+than	O
+0	O
+.	O
+05	O
+are	O
+considered	O
+evidence	O
+of	O
+adequate	O
+fit	O
+[	O
+23	O
+]	O
+.	O
+
+Reliability	O
+and	O
+stability	O
+
+Two	O
+forms	O
+of	O
+reliability	O
+were	O
+assessed	O
+:	O
+test	O
+-	O
+retest	O
+reliability	O
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+internal	O
+consistency	O
+reliability	O
+.	O
+
+Test	O
+-	O
+retest	O
+reliability	O
+,	O
+a	O
+measure	O
+of	O
+the	O
+degree	O
+to	O
+which	O
+the	O
+questionnaire	O
+yields	O
+stable	O
+scores	O
+over	O
+a	O
+short	O
+period	O
+of	O
+time	O
+(	O
+assuming	O
+there	O
+is	O
+no	O
+underlying	O
+change	O
+)	O
+,	O
+was	O
+measured	O
+by	O
+the	O
+intra	O
+-	O
+class	O
+correlation	O
+coefficient	O
+(	O
+ICC	O
+)	O
+[	O
+24	O
+,	O
+25	O
+]	O
+.	O
+
+An	O
+ICC	O
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+>	O
+=	O
+0	O
+.	O
+70	O
+was	O
+considered	O
+acceptable	O
+[	O
+26	O
+]	O
+.	O
+
+Internal	O
+consistency	O
+reliability	O
+,	O
+the	O
+extent	O
+to	O
+which	O
+items	O
+within	O
+each	O
+scale	O
+correlate	O
+with	O
+each	O
+other	O
+to	O
+form	O
+a	O
+multi	O
+-	O
+item	O
+scale	O
+,	O
+was	O
+assessed	O
+using	O
+Cronbach	O
+'	O
+s	O
+alpha	O
+[	O
+25	O
+,	O
+27	O
+]	O
+.	O
+
+Data	O
+from	O
+both	O
+assessments	O
+were	O
+used	O
+to	O
+evaluate	O
+internal	O
+consistency	O
+reliability	O
+.	O
+
+An	O
+alpha	O
+coefficient	O
+of	O
+>	O
+=	O
+0	O
+.	O
+70	O
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+considered	O
+acceptable	O
+,	O
+which	O
+is	O
+the	O
+commonly	O
+accepted	O
+minimal	O
+standard	O
+for	O
+reliability	O
+coefficients	O
+endorsed	O
+by	O
+the	O
+Scientific	O
+Advisory	O
+Committee	O
+of	O
+the	O
+Medical	O
+Outcomes	O
+Trust	O
+[	O
+26	O
+]	O
+.	O
+
+Construct	O
+Validity	O
+
+Construct	O
+validity	O
+was	O
+assessed	O
+by	O
+examining	O
+the	O
+inter	O
+-	O
+scale	O
+correlations	O
+between	O
+the	O
+ITP	O
+-	O
+PAQ	O
+and	O
+the	O
+CES	O
+-	O
+D	O
+and	O
+the	O
+ITP	O
+-	O
+PAQ	O
+with	O
+the	O
+SF	O
+-	O
+36	O
+and	O
+by	O
+examining	O
+the	O
+strength	O
+of	O
+the	O
+within	O
+ITP	O
+-	O
+PAQ	O
+scale	O
+correlations	O
+[	O
+25	O
+,	O
+28	O
+]	O
+.	O
+
+For	O
+both	O
+inter	O
+-	O
+scale	O
+and	O
+intra	O
+-	O
+scale	O
+correlations	O
+,	O
+we	O
+made	O
+a	O
+priori	O
+hypotheses	O
+about	O
+the	O
+directionality	O
+and	O
+magnitude	O
+of	O
+the	O
+correlation	O
+and	O
+observed	O
+the	O
+extent	O
+to	O
+which	O
+hypothesized	O
+relationships	O
+held	O
+.	O
+
+For	O
+example	O
+,	O
+we	O
+hypothesized	O
+that	O
+the	O
+scales	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+would	O
+be	O
+negatively	O
+correlated	O
+with	O
+the	O
+CES	O
+-	O
+D	O
+and	O
+positively	O
+correlated	O
+with	O
+those	O
+of	O
+the	O
+SF	O
+-	O
+36	O
+.	O
+
+We	O
+expected	O
+the	O
+Pearson	O
+correlations	O
+to	O
+be	O
+moderate	O
+in	O
+size	O
+.	O
+
+Known	O
+Groups	O
+
+Known	O
+groups	O
+validity	O
+evaluates	O
+the	O
+ability	O
+of	O
+the	O
+measure	O
+to	O
+discriminate	O
+between	O
+groups	O
+known	O
+to	O
+be	O
+clinically	O
+different	O
+[	O
+28	O
+]	O
+.	O
+
+We	O
+only	O
+collected	O
+patient	B
+-	O
+reported	O
+information	O
+using	O
+the	O
+questionnaire	O
+and	O
+did	O
+not	O
+collect	O
+clinical	O
+information	O
+such	O
+as	O
+platelet	O
+counts	O
+.	O
+
+Therefore	O
+,	O
+the	O
+following	O
+four	O
+criteria	O
+were	O
+identified	O
+as	O
+proxies	O
+for	O
+severity	O
+:	O
+
+*	O
+Currently	O
+on	O
+treatment	O
+
+*	O
+Splenectomy	O
+status	O
+
+*	O
+Subjects	O
+'	O
+self	O
+-	O
+perception	O
+of	O
+the	O
+effectiveness	O
+of	O
+current	O
+medication	O
+
+*	O
+Length	O
+of	O
+time	O
+since	O
+diagnosis	O
+
+It	O
+was	O
+hypothesized	O
+that	O
+subjects	O
+not	O
+being	O
+treated	O
+,	O
+who	O
+did	O
+not	O
+have	O
+a	O
+splenectomy	O
+,	O
+who	O
+perceived	O
+their	O
+medication	O
+to	O
+be	O
+more	O
+effective	O
+,	O
+and	O
+who	O
+had	O
+been	O
+diagnosed	O
+with	O
+ITP	O
+for	O
+a	O
+longer	O
+time	O
+would	O
+be	O
+healthier	O
+and	O
+therefore	O
+report	O
+higher	O
+HRQoL	O
+scores	O
+.	O
+
+In	O
+contrast	O
+,	O
+subjects	O
+on	O
+any	O
+treatment	O
+,	O
+who	O
+had	O
+received	O
+a	O
+splenectomy	O
+,	O
+who	O
+perceived	O
+their	O
+medication	O
+to	O
+be	O
+less	O
+effective	O
+,	O
+and	O
+who	O
+were	O
+diagnosed	O
+more	O
+recently	O
+would	O
+report	O
+worse	O
+HRQoL	O
+.	O
+
+In	O
+addition	O
+,	O
+subjects	O
+were	O
+also	O
+categorized	O
+by	O
+gender	O
+.	O
+
+Subjects	O
+were	O
+categorized	O
+into	O
+two	O
+groups	O
+for	O
+each	O
+of	O
+the	O
+analyses	O
+:	O
+female	O
+vs	O
+.	O
+male	O
+,	O
+intact	O
+spleen	O
+vs	O
+.	O
+removed	O
+spleen	O
+,	O
+currently	O
+on	O
+ITP	O
+treatment	O
+vs	O
+.	O
+not	O
+currently	O
+on	O
+ITP	O
+treatment	O
+,	O
+subject	O
+'	O
+s	O
+perception	O
+of	O
+the	O
+effectiveness	O
+of	O
+their	O
+current	O
+ITP	O
+medication	O
+(	O
+extremely	O
+/	O
+moderately	O
+effective	O
+vs	O
+.	O
+not	O
+at	O
+all	O
+effective	O
+)	O
+,	O
+and	O
+ITP	O
+diagnosis	O
+less	O
+than	O
+one	O
+year	O
+ago	O
+vs	O
+.	O
+ITP	O
+diagnosis	O
+more	O
+than	O
+one	O
+year	O
+ago	O
+.	O
+
+Results	O
+
+Demographics	O
+and	O
+clinical	O
+characteristics	O
+
+Table	O
+1	O
+describes	O
+the	O
+demographic	O
+and	O
+clinical	O
+characteristics	O
+of	O
+the	O
+73	O
+subjects	O
+included	O
+in	O
+the	O
+validation	O
+analyses	O
+.	O
+
+The	O
+majority	O
+were	O
+female	O
+(	O
+77	O
+%	O
+)	O
+and	O
+Caucasian	O
+(	O
+84	O
+%	O
+)	O
+.	O
+
+The	O
+mean	O
+age	O
+was	O
+45	O
+years	O
+(	O
+SD	O
+=	O
+15	O
+.	O
+7	O
+)	O
+,	O
+and	O
+most	O
+of	O
+the	O
+subjects	O
+had	O
+been	O
+diagnosed	O
+with	O
+ITP	O
+for	O
+at	O
+least	O
+five	O
+years	O
+(	O
+57	O
+%	O
+)	O
+.	O
+
+Fifty	O
+-	O
+two	O
+percent	O
+of	O
+the	O
+subjects	O
+reported	O
+that	O
+they	O
+were	O
+currently	O
+taking	O
+medications	O
+for	O
+their	O
+ITP	O
+.	O
+
+Furthermore	O
+,	O
+58	O
+%	O
+indicated	O
+that	O
+they	O
+had	O
+a	O
+splenectomy	O
+.	O
+
+Among	O
+the	O
+42	O
+subjects	O
+who	O
+had	O
+a	O
+splenectomy	O
+,	O
+55	O
+%	O
+reported	O
+that	O
+the	O
+removal	O
+of	O
+their	O
+spleen	O
+did	O
+not	O
+cure	O
+their	O
+ITP	O
+.	O
+
+With	O
+one	O
+exception	O
+,	O
+the	O
+remaining	O
+subjects	O
+did	O
+not	O
+provide	O
+a	O
+response	O
+.	O
+
+Confirmatory	O
+factor	O
+analysis	O
+
+The	O
+first	O
+confirmatory	O
+factor	O
+analysis	O
+of	O
+the	O
+50	O
+-	O
+item	O
+and	O
+ten	O
+factors	O
+model	O
+converged	O
+in	O
+28	O
+iterations	O
+.	O
+
+However	O
+,	O
+neither	O
+the	O
+inter	O
+-	O
+item	O
+correlation	O
+matrix	O
+nor	O
+the	O
+inter	O
+-	O
+factor	O
+correlation	O
+matrix	O
+was	O
+positive	O
+-	O
+definite	O
+,	O
+which	O
+suggests	O
+that	O
+the	O
+proposed	O
+model	O
+is	O
+wrong	O
+for	O
+the	O
+data	O
+or	O
+the	O
+data	O
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+inadequate	O
+for	O
+the	O
+model	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+chi	O
+-	O
+square	O
+value	O
+of	O
+the	O
+model	O
+was	O
+316	O
+.	O
+64	O
+with	O
+1129	O
+degrees	O
+of	O
+freedom	O
+(	O
+p	O
+=	O
+1	O
+.	O
+0	O
+)	O
+,	O
+which	O
+does	O
+not	O
+support	O
+the	O
+hypothesized	O
+scale	O
+structure	O
+of	O
+the	O
+initial	O
+ITP	O
+-	O
+PAQ	O
+.	O
+
+The	O
+confirmatory	O
+analysis	O
+of	O
+this	O
+LISREL	O
+model	O
+indicate	O
+that	O
+computing	O
+domain	O
+scores	O
+for	O
+the	O
+Physical	O
+Health	O
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+Mental	O
+Health	O
+domains	O
+is	O
+not	O
+appropriate	O
+for	O
+the	O
+ITP	O
+-	O
+PAQ	O
+.	O
+
+The	O
+second	O
+LISREL	O
+model	O
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+confirm	O
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+scale	O
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+,	O
+excluding	O
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+Reproductive	O
+Health	O
+scale	O
+.	O
+
+For	O
+this	O
+model	O
+,	O
+126	O
+parameters	O
+were	O
+estimated	O
+:	O
+46	O
+factor	O
+loadings	O
+,	O
+44	O
+error	O
+terms	O
+,	O
+and	O
+36	O
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+-	O
+factor	O
+correlations	O
+.	O
+
+The	O
+model	O
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+39	O
+iterations	O
+,	O
+with	O
+a	O
+chi	O
+-	O
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+1043	O
+.	O
+10	O
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+864	O
+degrees	O
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+freedom	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+The	O
+Goodness	O
+of	O
+Fit	O
+Index	O
+(	O
+GFI	O
+)	O
+,	O
+Normed	O
+Fit	O
+Index	O
+(	O
+NFI	O
+)	O
+,	O
+Non	O
+-	O
+normed	O
+Fit	O
+Index	O
+(	O
+NNFI	O
+)	O
+,	O
+and	O
+Comparative	O
+Fit	O
+Index	O
+(	O
+CFI	O
+)	O
+was	O
+0	O
+.	O
+60	O
+,	O
+0	O
+.	O
+63	O
+,	O
+0	O
+.	O
+91	O
+,	O
+and	O
+0	O
+.	O
+92	O
+,	O
+respectively	O
+,	O
+and	O
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+0	O
+.	O
+05	O
+[	O
+90	O
+%	O
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+,	O
+0	O
+.	O
+04	O
+-	O
+0	O
+.	O
+065	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+inter	O
+-	O
+factor	O
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+ranged	O
+form	O
+0	O
+.	O
+33	O
+between	O
+the	O
+Symptoms	O
+and	O
+Work	O
+scales	O
+to	O
+0	O
+.	O
+96	O
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+the	O
+Bother	O
+-	O
+Physical	O
+Health	O
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+Overall	O
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+.	O
+
+In	O
+addition	O
+to	O
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+factor	O
+analyses	O
+,	O
+Cronbach	O
+'	O
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+and	O
+item	O
+-	O
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+-	O
+total	O
+correlations	O
+were	O
+used	O
+for	O
+item	O
+reduction	O
+.	O
+
+Items	O
+with	O
+low	O
+factor	O
+loadings	O
+and	O
+item	O
+-	O
+to	O
+-	O
+total	O
+correlations	O
+that	O
+reduced	O
+the	O
+internal	O
+consistency	O
+were	O
+eliminated	O
+.	O
+
+Although	O
+initial	O
+factor	O
+analyses	O
+identified	O
+six	O
+domains	O
+for	O
+future	O
+use	O
+,	O
+the	O
+final	O
+version	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+contained	O
+44	O
+items	O
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+included	O
+the	O
+following	O
+ten	O
+scales	O
+:	O
+Symptoms	O
+,	O
+Bother	O
+-	O
+Physical	O
+Health	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+Overall	O
+QoL	O
+.	O
+
+Table	O
+2	O
+provides	O
+information	O
+on	O
+the	O
+number	O
+of	O
+items	O
+,	O
+item	O
+variability	O
+and	O
+sample	O
+items	O
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+each	O
+scale	O
+of	O
+the	O
+questionnaire	O
+.	O
+
+Each	O
+scale	O
+is	O
+scored	O
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+0	O
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+100	O
+,	O
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+higher	O
+scores	O
+representing	O
+better	O
+quality	O
+of	O
+life	O
+.	O
+
+Test	O
+-	O
+retest	O
+reliability	O
+
+Of	O
+the	O
+73	O
+subjects	O
+who	O
+completed	O
+the	O
+first	O
+administration	O
+of	O
+the	O
+questionnaire	O
+,	O
+most	O
+of	O
+the	O
+subjects	O
+completed	O
+the	O
+second	O
+questionnaire	O
+within	O
+a	O
+15	O
+-	O
+day	O
+period	O
+(	O
+75	O
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+)	O
+,	O
+during	O
+which	O
+subjects	O
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+expected	O
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+remain	O
+clinically	O
+stable	O
+.	O
+
+However	O
+,	O
+20	O
+%	O
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+the	O
+73	O
+subjects	O
+completed	O
+the	O
+questionnaire	O
+within	O
+three	O
+weeks	O
+following	O
+the	O
+first	O
+administration	O
+.	O
+
+The	O
+remaining	O
+5	O
+%	O
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+subjects	O
+completed	O
+it	O
+between	O
+four	O
+and	O
+nine	O
+weeks	O
+after	O
+the	O
+first	O
+"	O
+test	O
+.	O
+"	O
+ICC	O
+'	O
+s	O
+were	O
+computed	O
+for	O
+the	O
+entire	O
+sample	O
+(	O
+n	O
+=	O
+73	O
+)	O
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+for	O
+a	O
+sub	O
+-	O
+sample	O
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+respondents	O
+who	O
+completed	O
+the	O
+second	O
+questionnaire	O
+within	O
+three	O
+weeks	O
+(	O
+n	O
+=	O
+69	O
+)	O
+.	O
+
+With	O
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+Bother	O
+-	O
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+Activity	O
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+,	O
+all	O
+scales	O
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+acceptable	O
+test	O
+-	O
+retest	O
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+(	O
+ICC	O
+>	O
+=	O
+0	O
+.	O
+70	O
+)	O
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+by	O
+the	O
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+(	O
+Table	O
+3	O
+)	O
+.	O
+
+For	O
+the	O
+entire	O
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+,	O
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+0	O
+.	O
+52	O
+-	O
+0	O
+.	O
+90	O
+,	O
+while	O
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+for	O
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+-	O
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+from	O
+0	O
+.	O
+56	O
+-	O
+0	O
+.	O
+89	O
+.	O
+
+Internal	O
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+
+Internal	O
+consistency	O
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+,	O
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+by	O
+Cronbach	O
+'	O
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+,	O
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+0	O
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+66	O
+to	O
+0	O
+.	O
+92	O
+(	O
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+)	O
+.	O
+
+With	O
+the	O
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+,	O
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+'	O
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+the	O
+acceptable	O
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+of	O
+0	O
+.	O
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+.	O
+
+Cronbach	O
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+Symptoms	O
+,	O
+Bother	O
+-	O
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+,	O
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+/	O
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+,	O
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+0	O
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+71	O
+-	O
+0	O
+.	O
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+,	O
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+Health	O
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+Fear	O
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+0	O
+.	O
+87	O
+-	O
+0	O
+.	O
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+.	O
+
+Additionally	O
+,	O
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+,	O
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+,	O
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+Health	O
+,	O
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+Overall	O
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+were	O
+0	O
+.	O
+72	O
+,	O
+0	O
+.	O
+86	O
+,	O
+0	O
+.	O
+66	O
+,	O
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+0	O
+.	O
+89	O
+,	O
+respectively	O
+.	O
+
+Construct	O
+validity	O
+
+Table	O
+4	O
+displays	O
+the	O
+results	O
+of	O
+inter	O
+-	O
+scale	O
+Pearson	O
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+coefficients	O
+for	O
+the	O
+initial	O
+test	O
+administration	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+.	O
+
+As	O
+expected	O
+,	O
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+Symptoms	O
+,	O
+Bother	O
+-	O
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+Health	O
+,	O
+Fatigue	O
+/	O
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+,	O
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+to	O
+strongly	O
+inter	O
+-	O
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+on	O
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+data	O
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+the	O
+initial	O
+administration	O
+(	O
+correlation	O
+coefficients	O
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+0	O
+.	O
+56	O
+-	O
+0	O
+.	O
+75	O
+;	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+The	O
+Overall	O
+QoL	O
+scale	O
+was	O
+moderately	O
+to	O
+strongly	O
+correlated	O
+with	O
+the	O
+other	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+,	O
+with	O
+the	O
+exception	O
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+the	O
+Reproductive	O
+Health	O
+scale	O
+.	O
+
+In	O
+addition	O
+to	O
+examining	O
+the	O
+correlations	O
+within	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+,	O
+construct	O
+validity	O
+was	O
+also	O
+assessed	O
+by	O
+comparing	O
+the	O
+ITP	O
+-	O
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+scores	O
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+the	O
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+-	O
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+-	O
+36	O
+.	O
+
+The	O
+CES	O
+-	O
+D	O
+was	O
+negatively	O
+correlated	O
+with	O
+all	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+,	O
+except	O
+for	O
+the	O
+Reproductive	O
+Health	O
+scale	O
+.	O
+
+Other	O
+than	O
+the	O
+Reproductive	O
+Health	O
+scale	O
+,	O
+Pearson	O
+correlations	O
+ranged	O
+from	O
+-	O
+0	O
+.	O
+37	O
+to	O
+-	O
+0	O
+.	O
+70	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Most	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+were	O
+moderately	O
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+the	O
+SF	O
+-	O
+36	O
+scales	O
+;	O
+however	O
+,	O
+the	O
+Reproductive	O
+Health	O
+scale	O
+was	O
+not	O
+significantly	O
+correlated	O
+with	O
+any	O
+of	O
+the	O
+SF	O
+-	O
+36	O
+scales	O
+.	O
+
+The	O
+mean	O
+SF	O
+-	O
+36	O
+scores	O
+of	O
+the	O
+subjects	O
+with	O
+ITP	O
+were	O
+compared	O
+to	O
+those	O
+of	O
+the	O
+general	O
+U	O
+.	O
+S	O
+.	O
+population	O
+norms	O
+[	O
+15	O
+]	O
+.	O
+
+Results	O
+from	O
+t	O
+-	O
+tests	O
+indicate	O
+that	O
+there	O
+were	O
+statistically	O
+significant	O
+differences	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+in	O
+SF	O
+-	O
+36	O
+mean	O
+scores	O
+between	O
+subjects	O
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+ITP	O
+(	O
+range	O
+,	O
+43	O
+.	O
+04	O
+-	O
+72	O
+.	O
+86	O
+)	O
+and	O
+the	O
+general	O
+U	O
+.	O
+S	O
+.	O
+population	O
+(	O
+range	O
+,	O
+60	O
+.	O
+86	O
+-	O
+84	O
+.	O
+15	O
+)	O
+.	O
+
+Subjects	O
+with	O
+ITP	O
+reported	O
+lower	O
+scores	O
+on	O
+each	O
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+-	O
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+scale	O
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+to	O
+the	O
+US	O
+norm	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Known	O
+groups	O
+validity	O
+
+Subjects	O
+were	O
+categorized	O
+into	O
+two	O
+groups	O
+according	O
+to	O
+gender	O
+,	O
+splenectomy	O
+status	O
+,	O
+current	O
+ITP	O
+treatment	O
+status	O
+,	O
+subject	O
+'	O
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+perception	O
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+the	O
+effectiveness	O
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+ITP	O
+treatment	O
+,	O
+and	O
+time	O
+elapsed	O
+since	O
+ITP	O
+diagnosis	O
+.	O
+
+When	O
+subjects	O
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+to	O
+gender	O
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+splenectomy	O
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+,	O
+no	O
+statistically	O
+significant	O
+differences	O
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+any	O
+of	O
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+ITP	O
+-	O
+PAQ	O
+scales	O
+(	O
+data	O
+not	O
+shown	O
+)	O
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+
+Subjects	O
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+receiving	O
+treatment	O
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+ITP	O
+reported	O
+lower	O
+scores	O
+on	O
+all	O
+ITP	O
+-	O
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+to	O
+subjects	O
+who	O
+were	O
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+receiving	O
+treatment	O
+.	O
+
+Statistically	O
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+differences	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
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+reported	O
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+following	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+when	O
+subjects	O
+were	O
+categorized	O
+by	O
+treatment	O
+status	O
+:	O
+Symptoms	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+,	O
+Bother	O
+-	O
+Physical	O
+Health	O
+,	O
+Activity	O
+,	O
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+Health	O
+,	O
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+Overall	O
+QoL	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+When	O
+subjects	O
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+categorized	O
+by	O
+effectiveness	O
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+ITP	O
+treatment	O
+,	O
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+significant	O
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+(	O
+p	O
+<	O
+0	O
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+05	O
+)	O
+were	O
+observed	O
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+Symptoms	O
+and	O
+Activity	O
+scales	O
+(	O
+Figure	O
+1	O
+)	O
+,	O
+while	O
+statistically	O
+significant	O
+differences	O
+were	O
+only	O
+found	O
+for	O
+the	O
+Psychological	O
+Health	O
+scale	O
+when	O
+subjects	O
+were	O
+categorized	O
+according	O
+to	O
+time	O
+elapsed	O
+since	O
+ITP	O
+diagnosis	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Subjects	O
+who	O
+had	O
+been	O
+diagnosed	O
+with	O
+ITP	O
+for	O
+<	O
+1	O
+year	O
+had	O
+a	O
+lower	O
+mean	O
+score	O
+on	O
+the	O
+Psychological	O
+Health	O
+scale	O
+compared	O
+to	O
+subjects	O
+who	O
+had	O
+been	O
+diagnosed	O
+with	O
+ITP	O
+for	O
+at	O
+least	O
+one	O
+year	O
+(	O
+50	O
+.	O
+38	O
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+.	O
+66	O
+.	O
+46	O
+,	O
+respectively	O
+;	O
+p	O
+=	O
+0	O
+.	O
+02	O
+)	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Discussion	O
+
+The	O
+goal	O
+of	O
+this	O
+study	O
+was	O
+to	O
+develop	O
+and	O
+undertake	O
+initial	O
+validation	O
+analyses	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+as	O
+a	O
+tool	O
+for	O
+measuring	O
+HRQoL	O
+specifically	O
+related	O
+to	O
+adult	O
+subjects	O
+with	O
+ITP	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+study	O
+provide	O
+preliminary	O
+evidence	O
+of	O
+the	O
+reliability	O
+and	O
+validity	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+in	O
+this	O
+population	O
+.	O
+
+The	O
+results	O
+indicate	O
+that	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+the	O
+Reproductive	O
+Health	O
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+,	O
+the	O
+questionnaire	O
+has	O
+good	O
+internal	O
+consistency	O
+.	O
+
+The	O
+Reproductive	O
+Health	O
+scale	O
+may	O
+not	O
+have	O
+reached	O
+an	O
+acceptable	O
+level	O
+because	O
+the	O
+items	O
+could	O
+in	O
+fact	O
+be	O
+measuring	O
+slightly	O
+different	O
+concepts	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+Reproductive	O
+Health	O
+scale	O
+includes	O
+items	O
+that	O
+assess	O
+symptom	O
+bother	O
+related	O
+to	O
+menstruation	O
+in	O
+addition	O
+to	O
+items	O
+that	O
+ask	O
+how	O
+ITP	O
+impacts	O
+reproductive	O
+choices	O
+,	O
+such	O
+as	O
+becoming	O
+pregnant	O
+,	O
+giving	O
+birth	O
+,	O
+and	O
+adopting	O
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+.	O
+
+Perhaps	O
+,	O
+the	O
+symptom	O
+bother	O
+items	O
+in	O
+this	O
+scale	O
+may	O
+fit	O
+more	O
+appropriately	O
+with	O
+the	O
+Bother	O
+-	O
+Physical	O
+Health	O
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+,	O
+and	O
+the	O
+reproductive	O
+choice	O
+items	O
+could	O
+comprise	O
+a	O
+separate	O
+scale	O
+.	O
+
+Most	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+also	O
+demonstrated	O
+acceptable	O
+test	O
+-	O
+retest	O
+reliability	O
+,	O
+even	O
+though	O
+the	O
+time	O
+interval	O
+between	O
+test	O
+and	O
+retest	O
+administrations	O
+of	O
+the	O
+questionnaire	O
+exceeded	O
+the	O
+targeted	O
+time	O
+interval	O
+of	O
+seven	O
+to	O
+ten	O
+days	O
+.	O
+
+However	O
+,	O
+two	O
+scales	O
+,	O
+the	O
+Bother	O
+-	O
+Physical	O
+Health	O
+and	O
+Activity	O
+scales	O
+,	O
+reported	O
+ICC	O
+values	O
+below	O
+the	O
+acceptable	O
+value	O
+of	O
+0	O
+.	O
+70	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+lag	O
+between	O
+the	O
+two	O
+administrations	O
+of	O
+the	O
+questionnaire	O
+,	O
+subjects	O
+may	O
+have	O
+experienced	O
+an	O
+increase	O
+in	O
+bother	O
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+/	O
+or	O
+a	O
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+in	O
+activity	O
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+ITP	O
+during	O
+the	O
+extended	O
+time	O
+interval	O
+.	O
+
+Additionally	O
+,	O
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+low	O
+ICC	O
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+the	O
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+-	O
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+Health	O
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+Activity	O
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+be	O
+due	O
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+part	O
+to	O
+the	O
+relatively	O
+low	O
+number	O
+of	O
+items	O
+contained	O
+in	O
+each	O
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+these	O
+scales	O
+(	O
+four	O
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+two	O
+items	O
+,	O
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+)	O
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+to	O
+the	O
+Symptoms	O
+scale	O
+which	O
+contains	O
+six	O
+items	O
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+
+In	O
+general	O
+,	O
+the	O
+construct	O
+validity	O
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+the	O
+questionnaire	O
+was	O
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+by	O
+inter	O
+-	O
+scale	O
+correlations	O
+.	O
+
+As	O
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+,	O
+the	O
+Bother	O
+-	O
+Physical	O
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+,	O
+Symptoms	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+,	O
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+Activity	O
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+
+However	O
+,	O
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+it	O
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+-	O
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+-	O
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+,	O
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+-	O
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+,	O
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+concepts	O
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+by	O
+the	O
+items	O
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+this	O
+scale	O
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+all	O
+-	O
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+.	O
+
+Most	O
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+-	O
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+the	O
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+-	O
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+-	O
+D	O
+;	O
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+,	O
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+some	O
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+the	O
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+<	O
+0	O
+.	O
+40	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+Fear	O
+and	O
+SF	O
+-	O
+36	O
+Mental	O
+Health	O
+,	O
+0	O
+.	O
+30	O
+;	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+This	O
+low	O
+correlation	O
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+due	O
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+the	O
+ITP	O
+-	O
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+fear	O
+associated	O
+with	O
+ITP	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+fear	O
+of	O
+having	O
+a	O
+bleeding	O
+episode	O
+)	O
+,	O
+while	O
+the	O
+SF	O
+-	O
+36	O
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+a	O
+more	O
+general	O
+assessment	O
+of	O
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+health	O
+issues	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+felt	O
+downhearted	O
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+blue	O
+)	O
+.	O
+
+The	O
+known	O
+-	O
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+validity	O
+results	O
+indicate	O
+that	O
+some	O
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+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+(	O
+Symptoms	O
+,	O
+Fatigue	O
+/	O
+Sleep	O
+,	O
+Bother	O
+-	O
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+,	O
+Activity	O
+,	O
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+,	O
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+Overall	O
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+)	O
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+to	O
+differentiate	O
+ITP	O
+subjects	O
+who	O
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+currently	O
+receiving	O
+ITP	O
+treatment	O
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+those	O
+who	O
+were	O
+not	O
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+treatment	O
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+,	O
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+preliminary	O
+evidence	O
+of	O
+the	O
+ITP	O
+-	O
+PAQ	O
+'	O
+s	O
+ability	O
+to	O
+distinguish	O
+between	O
+groups	O
+known	O
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+be	O
+different	O
+.	O
+
+However	O
+,	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+were	O
+generally	O
+unable	O
+to	O
+distinguish	O
+between	O
+subjects	O
+when	O
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+were	O
+grouped	O
+by	O
+gender	O
+,	O
+splenectomy	O
+status	O
+,	O
+perceived	O
+effectiveness	O
+of	O
+treatment	O
+and	O
+length	O
+of	O
+time	O
+since	O
+ITP	O
+diagnosis	O
+.	O
+
+The	O
+ITP	O
+-	O
+PAQ	O
+may	O
+not	O
+be	O
+able	O
+to	O
+differentiate	O
+between	O
+female	O
+and	O
+male	O
+subjects	O
+because	O
+the	O
+disorder	O
+may	O
+affect	O
+females	O
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+males	O
+similarly	O
+.	O
+
+Additionally	O
+,	O
+significant	O
+differences	O
+may	O
+not	O
+have	O
+been	O
+observed	O
+between	O
+subjects	O
+who	O
+have	O
+undergone	O
+splenectomy	O
+and	O
+subjects	O
+who	O
+have	O
+not	O
+because	O
+55	O
+%	O
+of	O
+subjects	O
+who	O
+had	O
+a	O
+splenectomy	O
+indicated	O
+that	O
+it	O
+did	O
+not	O
+cure	O
+their	O
+ITP	O
+.	O
+
+Specifically	O
+,	O
+the	O
+known	O
+-	O
+groups	O
+could	O
+be	O
+defined	O
+as	O
+'	O
+subjects	O
+without	O
+a	O
+splenectomy	O
+'	O
+versus	O
+'	O
+subjects	O
+with	O
+a	O
+failed	O
+splenectomy	O
+'	O
+(	O
+for	O
+whom	O
+QoL	O
+likely	O
+worsened	O
+)	O
+versus	O
+'	O
+subjects	O
+with	O
+a	O
+successful	O
+splenectomy	O
+'	O
+(	O
+for	O
+whom	O
+QoL	O
+may	O
+have	O
+improved	O
+)	O
+.	O
+
+In	O
+the	O
+future	O
+,	O
+to	O
+assess	O
+whether	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+can	O
+differentiate	O
+between	O
+groups	O
+of	O
+subjects	O
+,	O
+it	O
+may	O
+be	O
+worthwhile	O
+to	O
+categorize	O
+subjects	O
+by	O
+a	O
+more	O
+clinically	O
+relevant	O
+measure	O
+,	O
+such	O
+as	O
+platelet	O
+count	O
+.	O
+
+Several	O
+limitations	O
+should	O
+be	O
+considered	O
+when	O
+interpreting	O
+our	O
+findings	O
+.	O
+
+Subjects	O
+were	O
+drawn	O
+from	O
+a	O
+convenience	O
+sample	O
+.	O
+
+The	O
+study	O
+population	O
+was	O
+fairly	O
+homogeneous	O
+,	O
+comprised	O
+primarily	O
+of	O
+Caucasian	O
+female	O
+subjects	O
+.	O
+
+The	O
+data	O
+was	O
+validated	O
+using	O
+only	O
+patient	B
+-	O
+reported	O
+data	O
+collected	O
+via	O
+questionnaire	O
+.	O
+
+The	O
+lack	O
+of	O
+clinical	O
+data	O
+in	O
+this	O
+initial	O
+validation	O
+study	O
+will	O
+be	O
+addressed	O
+in	O
+on	O
+-	O
+going	O
+pivotal	O
+trials	O
+that	O
+will	O
+collect	O
+clinical	O
+data	O
+such	O
+as	O
+platelet	O
+counts	O
+and	O
+platelet	O
+response	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+time	O
+interval	O
+between	O
+the	O
+initial	O
+and	O
+retest	O
+administration	O
+of	O
+the	O
+questionnaire	O
+may	O
+have	O
+been	O
+too	O
+lengthy	O
+to	O
+properly	O
+evaluate	O
+the	O
+test	O
+-	O
+retest	O
+reliability	O
+.	O
+
+Because	O
+25	O
+%	O
+of	O
+subjects	O
+did	O
+not	O
+complete	O
+the	O
+questionnaire	O
+within	O
+the	O
+targeted	O
+fifteen	O
+day	O
+interval	O
+,	O
+those	O
+subjects	O
+may	O
+have	O
+undergone	O
+clinical	O
+changes	O
+that	O
+may	O
+have	O
+affected	O
+their	O
+responses	O
+.	O
+
+In	O
+future	O
+validation	O
+studies	O
+platelet	O
+counts	O
+or	O
+type	O
+of	O
+platelet	O
+response	O
+should	O
+be	O
+used	O
+to	O
+identify	O
+a	O
+stable	O
+cohort	O
+for	O
+the	O
+test	O
+-	O
+retest	O
+analyses	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+criteria	O
+used	O
+to	O
+categorize	O
+the	O
+subjects	O
+for	O
+the	O
+known	O
+groups	O
+validity	O
+evaluation	O
+may	O
+not	O
+have	O
+been	O
+sufficient	O
+to	O
+allow	O
+for	O
+the	O
+ITP	O
+-	O
+PAQ	O
+scales	O
+to	O
+detect	O
+differences	O
+between	O
+groups	O
+.	O
+
+Grouping	O
+the	O
+subjects	O
+by	O
+a	O
+different	O
+criterion	O
+,	O
+such	O
+as	O
+a	O
+relevant	O
+clinical	O
+measure	O
+,	O
+may	O
+bolster	O
+the	O
+findings	O
+for	O
+its	O
+known	O
+groups	O
+validity	O
+.	O
+
+Conclusion	O
+
+The	O
+primary	O
+goal	O
+of	O
+this	O
+manuscript	O
+was	O
+to	O
+describe	O
+the	O
+development	O
+of	O
+a	O
+new	O
+ITP	O
+-	O
+specific	O
+HRQoL	O
+questionnaire	O
+for	O
+adults	O
+with	O
+ITP	O
+and	O
+to	O
+present	O
+our	O
+initial	O
+findings	O
+on	O
+the	O
+psychometric	O
+properties	O
+of	O
+this	O
+questionnaire	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+initial	O
+validation	O
+study	O
+indicate	O
+that	O
+the	O
+questionnaire	O
+generally	O
+has	O
+acceptable	O
+reliability	O
+and	O
+validity	O
+.	O
+
+We	O
+plan	O
+to	O
+conduct	O
+additional	O
+analyses	O
+using	O
+more	O
+objective	O
+clinical	O
+measures	O
+such	O
+as	O
+platelet	O
+counts	O
+as	O
+a	O
+criterion	O
+for	O
+known	O
+groups	O
+validity	O
+.	O
+
+Further	O
+validation	O
+work	O
+should	O
+also	O
+be	O
+conducted	O
+to	O
+assess	O
+its	O
+responsiveness	O
+and	O
+to	O
+estimate	O
+its	O
+minimal	O
+clinical	O
+important	O
+difference	O
+value	O
+so	O
+that	O
+it	O
+can	O
+become	O
+a	O
+more	O
+widely	O
+used	O
+HRQoL	O
+measure	O
+in	O
+the	O
+ITP	O
+population	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+validation	O
+study	O
+design	O
+,	O
+analysis	O
+,	O
+interpretation	O
+of	O
+results	O
+,	O
+and	O
+the	O
+writing	O
+of	O
+the	O
+manuscript	O
+represent	O
+the	O
+joint	O
+collaboration	O
+of	O
+all	O
+authors	O
+of	O
+this	O
+study	O
+,	O
+which	O
+was	O
+funded	O
+solely	O
+by	O
+Amgen	O
+,	O
+Inc	O
+,	O
+Thousand	O
+Oaks	O
+,	O
+California	O
+,	O
+USA	O
+.	O
+
+Ovation	O
+Research	O
+Group	O
+provided	O
+no	O
+additional	O
+funding	O
+for	O
+this	O
+study	O
+.	O
+
+The	O
+decision	O
+to	O
+submit	O
+this	O
+manuscript	O
+for	O
+publication	O
+was	O
+subject	O
+to	O
+the	O
+approval	O
+of	O
+Amgen	O
+,	O
+Inc	O
+.	O
+and	O
+all	O
+authors	O
+.	O
+
+Gary	O
+Okano	O
+and	O
+Janet	O
+Nichol	O
+are	O
+employees	O
+of	O
+Amgen	O
+,	O
+Inc	O
+.	O
+
+James	O
+Bussel	O
+is	O
+an	O
+employee	O
+of	O
+Weill	O
+Cornell	O
+Medical	O
+Center	O
+.	O
+
+James	O
+George	O
+is	O
+employed	O
+by	O
+the	O
+University	O
+of	O
+Oklahoma	O
+Health	O
+Sciences	O
+Center	O
+.	O
+
+Robert	O
+McMillan	O
+is	O
+a	O
+Professor	O
+Emeritus	O
+of	O
+the	O
+Scripps	O
+Research	O
+Institute	O
+.	O
+
+Susan	O
+Mathias	O
+is	O
+an	O
+employee	O
+of	O
+Ovation	O
+Research	O
+Group	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+SDM	O
+supervised	O
+the	O
+interpretation	O
+of	O
+the	O
+results	O
+from	O
+the	O
+validation	O
+study	O
+,	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+JBB	O
+,	O
+JNG	O
+,	O
+RM	O
+,	O
+and	O
+JLN	O
+provided	O
+clinical	O
+expertise	O
+in	O
+the	O
+development	O
+of	O
+the	O
+questionnaire	O
+,	O
+and	O
+participated	O
+in	O
+the	O
+design	O
+and	O
+execution	O
+of	O
+the	O
+study	O
+.	O
+
+GJO	O
+assisted	O
+in	O
+interpreting	O
+the	O
+results	O
+and	O
+drafting	O
+the	O
+manuscript	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Estrogen	O
+receptor	O
+alpha	O
+(	O
+ER	O
+alpha	O
+)	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+immunohistochemicall	O
+ER	O
+alpha	O
+-	O
+positive	O
+-	O
+,	O
+and	O
+negative	O
+breast	O
+cancer	O
+tissues	O
+
+Abstract	O
+
+Background	O
+
+The	O
+presence	O
+of	O
+ER	O
+alpha	O
+is	O
+the	O
+basis	O
+for	O
+treating	O
+breast	O
+cancer	O
+patients	B
+with	O
+targeted	O
+molecular	O
+therapies	O
+that	O
+block	O
+estrogen	O
+stimulation	O
+of	O
+breast	O
+cancer	O
+cell	O
+division	O
+.	O
+
+To	O
+select	O
+patients	B
+for	O
+the	O
+above	O
+therapies	O
+,	O
+currently	O
+,	O
+the	O
+ER	O
+alpha	O
+presence	O
+in	O
+breast	O
+cancer	O
+tissues	O
+is	O
+determined	O
+in	O
+clinical	O
+laboratories	O
+by	O
+microscopically	O
+scoring	O
+the	O
+slides	O
+subjected	O
+to	O
+immunohistochemistry	O
+(	O
+IHC	O
+)	O
+.	O
+
+This	O
+method	O
+is	O
+not	O
+quantitative	O
+,	O
+highly	O
+subjective	O
+and	O
+requires	O
+large	O
+amount	O
+of	O
+tumor	O
+tissue	O
+,	O
+therefore	O
+,	O
+cannot	O
+be	O
+applied	O
+to	O
+sterotactic	O
+and	O
+ultrasound	O
+guided	O
+biopsy	O
+samples	O
+.	O
+
+To	O
+circumvent	O
+these	O
+problems	O
+,	O
+we	O
+previously	O
+developed	O
+quantitative	O
+real	O
+-	O
+time	O
+PCR	O
+based	O
+molecular	O
+assay	O
+that	O
+can	O
+be	O
+applied	O
+to	O
+determine	O
+mRNA	O
+copies	O
+of	O
+ER	O
+alpha	O
+in	O
+picogram	O
+amounts	O
+of	O
+total	O
+RNA	O
+from	O
+tumor	O
+samples	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+not	O
+known	O
+how	O
+the	O
+mRNA	O
+copy	O
+numbers	O
+correlate	O
+to	O
+IHC	O
+positive	O
+and	O
+negative	O
+status	O
+.	O
+
+Methods	O
+
+In	O
+the	O
+current	O
+study	O
+we	O
+determined	O
+the	O
+copy	O
+numbers	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+by	O
+Q	O
+RTPCR	O
+in	O
+breast	O
+cancer	O
+tissues	O
+that	O
+were	O
+graded	O
+as	O
+ER	O
+alpha	O
+-	O
+positive	O
+and	O
+negative	O
+by	O
+1	O
+)	O
+IHC	O
+and	O
+2	O
+)	O
+functional	O
+estrogen	O
+binding	O
+assay	O
+and	O
+statistically	O
+analyzed	O
+the	O
+data	O
+.	O
+
+Results	O
+
+We	O
+demonstrate	O
+here	O
+that	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+are	O
+not	O
+significantly	O
+different	O
+in	O
+tissues	O
+that	O
+are	O
+graded	O
+as	O
+positive	O
+by	O
+IHC	O
+and	O
+ligand	O
+binding	O
+assays	O
+.	O
+
+We	O
+establish	O
+here	O
+a	O
+cut	O
+of	O
+value	O
+of	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+mRNA	O
+copies	O
+of	O
+GAPDH	O
+with	O
+an	O
+Odds	O
+Radio	O
+of	O
+39	O
+.	O
+4	O
+,	O
+Sensitivity	O
+of	O
+0	O
+.	O
+81	O
+and	O
+Specificity	O
+of	O
+0	O
+.	O
+90	O
+in	O
+breast	O
+cancer	O
+tissues	O
+that	O
+are	O
+negative	O
+for	O
+ER	O
+alpha	O
+protein	O
+by	O
+IHC	O
+and	O
+estrogen	O
+binding	O
+assays	O
+.	O
+
+ROC	O
+analysis	O
+of	O
+the	O
+data	O
+gave	O
+an	O
+area	O
+of	O
+0	O
+.	O
+8967	O
+under	O
+the	O
+curve	O
+.	O
+
+Conclusion	O
+
+We	O
+expect	O
+that	O
+the	O
+cut	O
+off	O
+values	O
+determined	O
+here	O
+will	O
+be	O
+highly	O
+significant	O
+for	O
+applying	O
+molecular	O
+assay	O
+in	O
+the	O
+place	O
+of	O
+IHC	O
+in	O
+clinical	O
+laboratories	O
+for	O
+evaluating	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+for	O
+prognostic	O
+and	O
+therapeutic	O
+purposes	O
+.	O
+
+Background	O
+
+Breast	O
+cancer	O
+is	O
+the	O
+most	O
+diagnosed	O
+and	O
+the	O
+second	O
+leading	O
+cause	O
+of	O
+cancer	O
+deaths	O
+for	O
+women	B
+in	O
+the	O
+United	O
+States	O
+striking	O
+about	O
+300	O
+,	O
+000	O
+and	O
+killing	O
+about	O
+40	O
+,	O
+000	O
+women	B
+a	O
+year	O
+[	O
+1	O
+]	O
+.	O
+
+A	O
+substantial	O
+body	O
+of	O
+epidemiological	O
+,	O
+experimental	O
+and	O
+clinical	O
+evidence	O
+indicated	O
+that	O
+unopposed	O
+stimulation	O
+of	O
+breast	O
+epithelial	O
+cells	O
+by	O
+the	O
+natural	O
+hormone	O
+,	O
+estrogen	O
+,	O
+plays	O
+a	O
+major	O
+role	O
+in	O
+the	O
+progression	O
+of	O
+breast	O
+cancers	O
+[	O
+2	O
+]	O
+.	O
+
+Because	O
+endogenous	O
+estrogens	O
+directly	O
+promote	O
+the	O
+growth	O
+of	O
+breast	O
+cancer	O
+cells	O
+,	O
+estrogen	O
+deprivation	O
+either	O
+by	O
+inhibiting	O
+its	O
+biosynthesis	O
+(	O
+aromatase	O
+inhibitors	O
+)	O
+or	O
+blocking	O
+estrogen	O
+-	O
+mediated	O
+gene	O
+transcription	O
+(	O
+tamoxifen	O
+)	O
+through	O
+its	O
+high	O
+affinity	O
+receptor	O
+,	O
+the	O
+estrogen	O
+receptor	O
+alpha	O
+(	O
+ER	O
+alpha	O
+)	O
+,	O
+are	O
+the	O
+primary	O
+lines	O
+of	O
+therapy	O
+for	O
+breast	O
+cancer	O
+patients	B
+.	O
+
+In	O
+most	O
+cases	O
+,	O
+the	O
+efficacy	O
+of	O
+the	O
+above	O
+treatments	O
+has	O
+correlated	O
+with	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+in	O
+the	O
+tumor	O
+tissues	O
+.	O
+
+Currently	O
+,	O
+only	O
+those	O
+patients	B
+who	O
+express	O
+ER	O
+alpha	O
+in	O
+their	O
+tumors	O
+are	O
+chosen	O
+for	O
+aromatase	O
+inhibitor	O
+or	O
+tamoxifen	O
+therapies	O
+.	O
+
+In	O
+addition	O
+to	O
+being	O
+a	O
+therapeutic	O
+target	O
+,	O
+ER	O
+alpha	O
+was	O
+also	O
+shown	O
+to	O
+be	O
+the	O
+most	O
+important	O
+factor	O
+to	O
+predict	O
+breast	O
+cancer	O
+prognosis	O
+.	O
+
+The	O
+patients	B
+who	O
+express	O
+ER	O
+alpha	O
+in	O
+their	O
+tumors	O
+have	O
+an	O
+overall	O
+longer	O
+cancer	O
+-	O
+free	O
+survival	O
+and	O
+lower	O
+recurrence	O
+rates	O
+than	O
+patients	B
+who	O
+do	O
+not	O
+express	O
+this	O
+receptor	O
+[	O
+3	O
+]	O
+.	O
+
+To	O
+predict	O
+prognosis	O
+and	O
+identify	O
+patients	B
+for	O
+the	O
+above	O
+two	O
+anti	O
+-	O
+estrogen	O
+therapies	O
+,	O
+every	O
+breast	O
+cancer	O
+tissue	O
+is	O
+currently	O
+screened	O
+for	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+before	O
+a	O
+treatment	O
+regimen	O
+is	O
+selected	O
+for	O
+any	O
+breast	O
+cancer	O
+patient	B
+.	O
+
+The	O
+presence	O
+of	O
+ER	O
+alpha	O
+in	O
+breast	O
+tumors	O
+was	O
+originally	O
+determined	O
+in	O
+clinical	O
+labs	O
+by	O
+estrogen	O
+binding	O
+assay	O
+for	O
+about	O
+20	O
+years	O
+.	O
+
+However	O
+,	O
+when	O
+the	O
+tumors	O
+were	O
+detected	O
+at	O
+comparatively	O
+smaller	O
+sizes	O
+and	O
+highly	O
+specific	O
+monoclonal	O
+antibodies	O
+were	O
+developed	O
+that	O
+could	O
+detect	O
+ER	O
+alpha	O
+both	O
+in	O
+the	O
+fresh	O
+frozen	O
+as	O
+well	O
+as	O
+formalin	O
+fixed	O
+paraffin	O
+-	O
+embedded	O
+tissues	O
+,	O
+the	O
+clinical	O
+labs	O
+switched	O
+to	O
+immunohistochemistry	O
+(	O
+IHC	O
+)	O
+from	O
+estrogen	O
+binding	O
+assay	O
+for	O
+determining	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+.	O
+
+Currently	O
+ER	O
+alpha	O
+is	O
+determined	O
+in	O
+the	O
+clinical	O
+laboratories	O
+from	O
+rough	O
+estimates	O
+yielded	O
+by	O
+microscopically	O
+scoring	O
+the	O
+slides	O
+subjected	O
+to	O
+IHC	O
+technique	O
+using	O
+antibodies	O
+against	O
+the	O
+N	O
+-	O
+terminal	O
+A	O
+/	O
+B	O
+region	O
+of	O
+ER	O
+alpha	O
+.	O
+
+Although	O
+this	O
+procedure	O
+is	O
+used	O
+for	O
+over	O
+ten	O
+years	O
+,	O
+it	O
+has	O
+several	O
+limitations	O
+including	O
+not	O
+quantitative	O
+,	O
+highly	O
+subjective	O
+,	O
+variations	O
+due	O
+to	O
+antibody	O
+preparations	O
+,	O
+variations	O
+from	O
+one	O
+clinical	O
+lab	O
+to	O
+other	O
+and	O
+comparatively	O
+large	O
+sample	O
+size	O
+requirement	O
+.	O
+
+In	O
+recent	O
+times	O
+,	O
+due	O
+to	O
+increased	O
+awareness	O
+and	O
+substantially	O
+improved	O
+screening	O
+methods	O
+,	O
+breast	O
+cancers	O
+are	O
+detected	O
+at	O
+very	O
+early	O
+stages	O
+and	O
+excised	O
+,	O
+in	O
+a	O
+large	O
+majority	O
+of	O
+cases	O
+,	O
+by	O
+stereotactic	O
+and	O
+ultrasound	O
+guided	O
+techniques	O
+.	O
+
+In	O
+these	O
+cases	O
+the	O
+limited	O
+amount	O
+of	O
+tumor	O
+tissue	O
+that	O
+remains	O
+after	O
+histological	O
+testing	O
+restricts	O
+determining	O
+ER	O
+alpha	O
+status	O
+for	O
+prognostic	O
+and	O
+therapeutic	O
+purposes	O
+by	O
+IHC	O
+.	O
+
+In	O
+many	O
+cases	O
+,	O
+ER	O
+alpha	O
+status	O
+is	O
+not	O
+determined	O
+due	O
+to	O
+insufficient	O
+amount	O
+of	O
+tumor	O
+tissue	O
+.	O
+
+For	O
+these	O
+reasons	O
+there	O
+is	O
+an	O
+urgent	O
+need	O
+to	O
+switch	O
+to	O
+a	O
+procedure	O
+that	O
+can	O
+detect	O
+ER	O
+alpha	O
+in	O
+a	O
+very	O
+small	O
+amount	O
+of	O
+tumor	O
+tissue	O
+obtained	O
+by	O
+the	O
+above	O
+methods	O
+.	O
+
+There	O
+is	O
+a	O
+general	O
+consensus	O
+that	O
+ER	O
+alpha	O
+mRNA	O
+quantification	O
+is	O
+a	O
+more	O
+suited	O
+technique	O
+for	O
+detecting	O
+its	O
+presence	O
+in	O
+tumor	O
+tissues	O
+.	O
+
+Several	O
+PCR	O
+based	O
+approaches	O
+have	O
+been	O
+described	O
+for	O
+detecting	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+in	O
+breast	O
+cancer	O
+tissues	O
+[	O
+4	O
+,	O
+5	O
+]	O
+.	O
+
+We	O
+recently	O
+developed	O
+a	O
+highly	O
+sensitive	O
+real	O
+-	O
+time	O
+PCR	O
+based	O
+quantitative	O
+molecular	O
+assay	O
+that	O
+can	O
+detect	O
+and	O
+quantify	O
+as	O
+low	O
+as	O
+50	O
+-	O
+100	O
+copies	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+from	O
+as	O
+small	O
+as	O
+40	O
+picograms	O
+of	O
+total	O
+RNA	O
+from	O
+breast	O
+cancer	O
+tissues	O
+.	O
+
+Because	O
+quantitative	O
+real	O
+-	O
+time	O
+PCR	O
+is	O
+a	O
+high	O
+through	O
+-	O
+put	O
+method	O
+,	O
+it	O
+could	O
+be	O
+automated	O
+to	O
+apply	O
+in	O
+clinical	O
+laboratories	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+not	O
+known	O
+how	O
+the	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+correlate	O
+to	O
+ER	O
+alpha	O
+positivity	O
+and	O
+negativity	O
+by	O
+IHC	O
+assay	O
+.	O
+
+Establishing	O
+a	O
+cut	O
+off	O
+value	O
+in	O
+IHC	O
+negative	O
+tissues	O
+is	O
+required	O
+for	O
+the	O
+application	O
+of	O
+molecular	O
+assay	O
+in	O
+the	O
+place	O
+of	O
+IHC	O
+assay	O
+.	O
+
+To	O
+determine	O
+the	O
+cut	O
+off	O
+value	O
+,	O
+we	O
+have	O
+profiled	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+breast	O
+cancer	O
+tissues	O
+which	O
+have	O
+been	O
+graded	O
+as	O
+ER	O
+alpha	O
+positive	O
+and	O
+negative	O
+by	O
+IHC	O
+and	O
+estrogen	O
+binding	O
+assays	O
+.	O
+
+We	O
+demonstrate	O
+here	O
+that	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+are	O
+not	O
+significantly	O
+different	O
+in	O
+tissues	O
+that	O
+were	O
+graded	O
+as	O
+positive	O
+by	O
+IHC	O
+and	O
+ligand	O
+binding	O
+assays	O
+.	O
+
+However	O
+,	O
+ER	O
+alpha	O
+positive	O
+tissues	O
+,	O
+either	O
+by	O
+IHC	O
+or	O
+estrogen	O
+binding	O
+assays	O
+,	O
+express	O
+significantly	O
+higher	O
+mRNA	O
+copy	O
+numbers	O
+than	O
+the	O
+negative	O
+tissues	O
+.	O
+
+We	O
+have	O
+determined	O
+the	O
+cut	O
+off	O
+values	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+by	O
+molecular	O
+assay	O
+that	O
+correlate	O
+to	O
+ER	O
+alpha	O
+negativity	O
+by	O
+both	O
+IHC	O
+and	O
+ligand	O
+binding	O
+assays	O
+using	O
+CART	O
+program	O
+(	O
+Classification	O
+And	O
+Regression	O
+Tree	O
+)	O
+.	O
+
+We	O
+expect	O
+that	O
+the	O
+cut	O
+off	O
+values	O
+determined	O
+here	O
+will	O
+be	O
+highly	O
+significant	O
+for	O
+applying	O
+molecular	O
+assay	O
+in	O
+the	O
+place	O
+of	O
+IHC	O
+in	O
+clinical	O
+laboratories	O
+for	O
+determining	O
+the	O
+ER	O
+alpha	O
+status	O
+for	O
+prognostic	O
+and	O
+therapeutic	O
+purposes	O
+.	O
+
+Methods	O
+
+All	O
+the	O
+primers	O
+used	O
+in	O
+the	O
+current	O
+study	O
+were	O
+synthesized	O
+by	O
+Gibco	O
+-	O
+BRL	O
+Life	O
+Technologies	O
+.	O
+
+TaqMan	O
+Universal	O
+PCR	O
+Master	O
+Mix	O
+(	O
+Cat	O
+#	O
+4304437	O
+)	O
+was	O
+from	O
+Applied	O
+Biosystems	O
+.	O
+
+5	O
+'	O
+FAM	O
+and	O
+3	O
+'	O
+TAMARA	O
+labeled	O
+oligonucleotide	O
+probes	O
+were	O
+synthesized	O
+by	O
+Applied	O
+Biosystems	O
+and	O
+available	O
+from	O
+previous	O
+studies	O
+.	O
+
+PCR	O
+quality	O
+water	O
+and	O
+Tris	O
+-	O
+EDTA	O
+buffer	O
+were	O
+from	O
+BioWhittaker	O
+.	O
+
+Breast	O
+tumor	O
+samples	O
+
+Breast	O
+cancer	O
+tissues	O
+with	O
+known	O
+ER	O
+alpha	O
+status	O
+by	O
+IHC	O
+and	O
+ligand	O
+binding	O
+assay	O
+were	O
+available	O
+from	O
+previous	O
+studies	O
+[	O
+6	O
+-	O
+9	O
+]	O
+.	O
+
+Briefly	O
+,	O
+the	O
+tumor	O
+samples	O
+were	O
+collected	O
+from	O
+either	O
+biopsy	O
+or	O
+mastectomies	O
+immediately	O
+after	O
+surgery	O
+and	O
+stored	O
+at	O
+-	O
+80	O
+degrees	O
+C	O
+until	O
+use	O
+.	O
+
+Fresh	O
+tumor	O
+tissue	O
+samples	O
+for	O
+ER	O
+alpha	O
+quantification	O
+were	O
+routinely	O
+harvested	O
+immediately	O
+adjacent	O
+to	O
+the	O
+histologic	O
+/	O
+diagnostic	O
+sections	O
+and	O
+considered	O
+to	O
+be	O
+representative	O
+of	O
+the	O
+tissue	O
+used	O
+for	O
+diagnosis	O
+.	O
+
+All	O
+the	O
+samples	O
+were	O
+examined	O
+by	O
+a	O
+pathologist	O
+and	O
+tissues	O
+containing	O
+>	O
+80	O
+%	O
+cancer	O
+cells	O
+were	O
+excised	O
+and	O
+used	O
+for	O
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+alpha	O
+mRNA	O
+quantification	O
+.	O
+
+The	O
+ER	O
+alpha	O
+-	O
+status	O
+for	O
+the	O
+samples	O
+used	O
+in	O
+this	O
+study	O
+was	O
+determined	O
+either	O
+by	O
+IHC	O
+using	O
+monoclonal	O
+antibodies	O
+against	O
+NH2	O
+-	O
+terminal	O
+portion	O
+of	O
+the	O
+molecule	O
+at	O
+Oncotech	O
+Laboratories	O
+,	O
+Irwine	O
+,	O
+CA	O
+,	O
+or	O
+by	O
+ligand	O
+binding	O
+assay	O
+as	O
+described	O
+[	O
+10	O
+]	O
+.	O
+
+The	O
+tumor	O
+tissues	O
+were	O
+considered	O
+positive	O
+for	O
+ER	O
+alpha	O
+by	O
+IHC	O
+if	O
+>	O
+5	O
+%	O
+of	O
+cancer	O
+cells	O
+showed	O
+positive	O
+nuclear	O
+staining	O
+.	O
+
+The	O
+tumor	O
+tissues	O
+that	O
+were	O
+diagnosed	O
+as	O
+ER	O
+alpha	O
+positive	O
+by	O
+estrogen	O
+binding	O
+assay	O
+had	O
+>	O
+3	O
+fmol	O
+of	O
+ER	O
+/	O
+mg	O
+of	O
+total	O
+tissue	O
+extract	O
+.	O
+
+A	O
+total	O
+of	O
+70	O
+samples	O
+positive	O
+by	O
+IHC	O
+,	O
+33	O
+positive	O
+by	O
+estrogen	O
+binding	O
+assay	O
+,	O
+43	O
+negative	O
+by	O
+IHC	O
+and	O
+20	O
+negative	O
+by	O
+estrogen	O
+binding	O
+assay	O
+were	O
+included	O
+in	O
+the	O
+current	O
+study	O
+(	O
+Tables	O
+1	O
+,	O
+2	O
+,	O
+3	O
+and	O
+4	O
+respectively	O
+)	O
+.	O
+
+The	O
+tumor	O
+tissues	O
+were	O
+processed	O
+to	O
+isolate	O
+total	O
+RNA	O
+and	O
+cDNAs	O
+prepared	O
+as	O
+previously	O
+described	O
+[	O
+6	O
+-	O
+9	O
+]	O
+.	O
+
+Howard	O
+University	O
+Institutional	O
+Review	O
+Board	O
+granted	O
+the	O
+ethical	O
+approval	O
+of	O
+Tumor	O
+collection	O
+procedures	O
+for	O
+the	O
+study	O
+.	O
+
+Absolute	O
+quantification	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+by	O
+quantitative	O
+real	O
+-	O
+time	O
+PCR	O
+
+Absolute	O
+quantification	O
+of	O
+ER	O
+alpha	O
+transcript	O
+copy	O
+numbers	O
+was	O
+achieved	O
+by	O
+quantitative	O
+real	O
+-	O
+time	O
+PCR	O
+in	O
+ABI	O
+Prism	O
+GeneAmp	O
+7900	O
+HT	O
+Sequence	O
+Detection	O
+System	O
+as	O
+described	O
+previously	O
+(	O
+9	O
+)	O
+.	O
+
+Briefly	O
+,	O
+a	O
+typical	O
+real	O
+-	O
+time	O
+PCR	O
+reaction	O
+mixture	O
+contained	O
+cDNA	O
+prepared	O
+from	O
+reverse	O
+transcription	O
+of	O
+0	O
+.	O
+5	O
+-	O
+5	O
+nanograms	O
+of	O
+tumor	O
+tissue	O
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+RNA	O
+,	O
+0	O
+.	O
+04	O
+micromolar	O
+each	O
+of	O
+sense	O
+and	O
+anti	O
+-	O
+sense	O
+primers	O
+,	O
+0	O
+.	O
+05	O
+micromolar	O
+5	O
+'	O
+FAM	O
+and	O
+3	O
+'	O
+TAMARA	O
+labeled	O
+oligonucleotide	O
+probe	O
+and	O
+1	O
+x	O
+Taqman	O
+Universal	O
+PCR	O
+Mix	O
+in	O
+a	O
+total	O
+volume	O
+of	O
+25	O
+mu	O
+l	O
+.	O
+
+PCR	O
+conditions	O
+were	O
+initial	O
+hold	O
+at	O
+50	O
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+for	O
+two	O
+minutes	O
+,	O
+followed	O
+by	O
+denaturation	O
+for	O
+ten	O
+minutes	O
+at	O
+95	O
+degrees	O
+C	O
+,	O
+and	O
+denaturation	O
+for	O
+15	O
+seconds	O
+at	O
+95	O
+degrees	O
+C	O
+in	O
+the	O
+subsequent	O
+cycles	O
+and	O
+annealing	O
+and	O
+extension	O
+for	O
+1	O
+min	O
+at	O
+60	O
+degrees	O
+C	O
+for	O
+40	O
+cycles	O
+.	O
+
+The	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+tumor	O
+tissues	O
+were	O
+determined	O
+in	O
+comparison	O
+with	O
+a	O
+standard	O
+graph	O
+constructed	O
+simultaneously	O
+using	O
+102	O
+,	O
+103	O
+,	O
+104	O
+,	O
+105	O
+,	O
+106	O
+,	O
+107	O
+,	O
+108	O
+,	O
+and	O
+109	O
+copies	O
+of	O
+reverse	O
+transcribed	O
+cRNA	O
+of	O
+ER	O
+alpha	O
+.	O
+
+All	O
+the	O
+samples	O
+were	O
+amplified	O
+in	O
+triplicate	O
+and	O
+real	O
+-	O
+time	O
+PCRs	O
+were	O
+repeated	O
+four	O
+times	O
+.	O
+
+The	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+tumor	O
+tissues	O
+were	O
+normalized	O
+to	O
+mRNA	O
+copy	O
+numbers	O
+of	O
+the	O
+house	O
+keeping	O
+gene	O
+,	O
+glyceraldehyde	O
+3	O
+-	O
+phosphate	O
+dehydrogenase	O
+(	O
+GAPDH	O
+)	O
+.	O
+
+GAPDH	O
+copy	O
+numbers	O
+were	O
+determined	O
+as	O
+previously	O
+described	O
+[	O
+11	O
+,	O
+12	O
+]	O
+.	O
+
+The	O
+sense	O
+,	O
+and	O
+anti	O
+-	O
+sense	O
+primers	O
+and	O
+probe	O
+for	O
+quantifying	O
+the	O
+mRNA	O
+copy	O
+numbers	O
+of	O
+ER	O
+alpha	O
+were	O
+5	O
+'	O
+caagcccgctcatgatcaa	O
+3	O
+'	O
+(	O
+position	O
+,	O
+exon	O
+4	O
+,	O
+bp	O
+1110	O
+-	O
+1128	O
+)	O
+,	O
+5	O
+'	O
+ctgatcatggagggtcaaat	O
+'	O
+(	O
+position	O
+,	O
+exon	O
+5	O
+,	O
+bp	O
+1358	O
+-	O
+1338	O
+)	O
+and	O
+FAM	O
+5	O
+'	O
+agaacagcctggccttgtcc	O
+'	O
+TAMARA	O
+(	O
+position	O
+,	O
+exon	O
+4	O
+,	O
+bp	O
+1140	O
+-	O
+1162	O
+)	O
+respectively	O
+.	O
+
+The	O
+sense	O
+and	O
+anti	O
+-	O
+sense	O
+primers	O
+and	O
+probe	O
+for	O
+quantifying	O
+GAPDH	O
+mRNA	O
+copy	O
+numbers	O
+were	O
+5	O
+'	O
+ttccagg	O
+agcgag	O
+atccct3	O
+'	O
+(	O
+position	O
+,	O
+bp	O
+304	O
+-	O
+322	O
+)	O
+,	O
+5	O
+'	O
+ggctgttgtcatacttctca	O
+'	O
+(	O
+position	O
+,	O
+bp	O
+483	O
+-	O
+505	O
+)	O
+and	O
+FAM	O
+5	O
+'	O
+tgctggcgctgagtacgtcg	O
+'	O
+TAMARA	O
+(	O
+position	O
+,	O
+bp	O
+342	O
+-	O
+363	O
+)	O
+respectively	O
+.	O
+
+Primer	O
+positions	O
+of	O
+ER	O
+alpha	O
+and	O
+GAPDH	O
+nucleotide	O
+sequences	O
+were	O
+as	O
+described	O
+[	O
+13	O
+,	O
+14	O
+]	O
+.	O
+
+Statistical	O
+analysis	O
+
+Wilcoxon	O
+-	O
+rank	O
+-	O
+sum	O
+test	O
+and	O
+standard	O
+two	O
+-	O
+sample	O
+t	O
+-	O
+test	O
+were	O
+used	O
+to	O
+determine	O
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+the	O
+mRNA	O
+copy	O
+numbers	O
+were	O
+significantly	O
+different	O
+in	O
+breast	O
+cancer	O
+tissues	O
+that	O
+were	O
+1	O
+)	O
+ER	O
+alpha	O
+-	O
+positive	O
+and	O
+ER	O
+alpha	O
+-	O
+negative	O
+by	O
+IHC	O
+,	O
+2	O
+)	O
+ER	O
+alpha	O
+-	O
+positive	O
+and	O
+ER	O
+alpha	O
+-	O
+negative	O
+by	O
+estrogen	O
+binding	O
+assays	O
+,	O
+3	O
+)	O
+ER	O
+alpha	O
+positive	O
+by	O
+IHC	O
+and	O
+estrogen	O
+binding	O
+assays	O
+,	O
+and	O
+4	O
+)	O
+ER	O
+alpha	O
+-	O
+negative	O
+by	O
+IHC	O
+and	O
+estrogen	O
+binding	O
+assays	O
+.	O
+
+Test	O
+results	O
+were	O
+considered	O
+significant	O
+if	O
+P	O
+<	O
+=	O
+0	O
+.	O
+
+05	O
+.	O
+
+To	O
+determine	O
+the	O
+cut	O
+-	O
+off	O
+value	O
+/	O
+maximum	O
+level	O
+of	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+the	O
+samples	O
+which	O
+were	O
+negative	O
+by	O
+IHC	O
+and	O
+estrogen	O
+binding	O
+assays	O
+,	O
+we	O
+used	O
+CART	O
+(	O
+Classification	O
+Regression	O
+Tree	O
+)	O
+[	O
+15	O
+,	O
+16	O
+]	O
+program	O
+.	O
+
+The	O
+data	O
+consisting	O
+of	O
+103	O
+ER	O
+alpha	O
+positive	O
+and	O
+63	O
+ER	O
+alpha	O
+negative	O
+samples	O
+which	O
+had	O
+a	O
+predictive	O
+variable	O
+,	O
+mRNA	O
+copy	O
+numbers	O
+,	O
+were	O
+partitioned	O
+into	O
+two	O
+groups	O
+using	O
+CART	O
+program	O
+.	O
+
+This	O
+program	O
+determines	O
+the	O
+best	O
+cut	O
+-	O
+off	O
+value	O
+copy	O
+numbers	O
+in	O
+the	O
+sense	O
+that	O
+the	O
+OR	O
+(	O
+Odds	O
+Ratio	O
+,	O
+ER	O
+alpha	O
+positive	O
+to	O
+ER	O
+alpha	O
+negative	O
+in	O
+our	O
+case	O
+)	O
+of	O
+the	O
+two	O
+groups	O
+(	O
+with	O
+copy	O
+number	O
+greater	O
+than	O
+the	O
+cut	O
+-	O
+off	O
+value	O
+in	O
+one	O
+group	O
+and	O
+less	O
+or	O
+equal	O
+to	O
+the	O
+cut	O
+-	O
+off	O
+value	O
+in	O
+the	O
+other	O
+)	O
+is	O
+maximized	O
+.	O
+
+Receiver	O
+Operating	O
+Characteristic	O
+(	O
+ROC	O
+)	O
+analysis	O
+was	O
+performed	O
+to	O
+determine	O
+the	O
+sensitivity	O
+and	O
+specificity	O
+of	O
+the	O
+RNA	O
+based	O
+molecular	O
+assay	O
+.	O
+
+The	O
+ROC	O
+curves	O
+were	O
+generated	O
+by	O
+connecting	O
+all	O
+the	O
+points	O
+determined	O
+by	O
+the	O
+copy	O
+numbers	O
+in	O
+all	O
+the	O
+samples	O
+in	O
+an	O
+increasing	O
+order	O
+.	O
+
+Since	O
+data	O
+on	O
+IHC	O
+grading	O
+as	O
+percent	O
+positive	O
+cells	O
+were	O
+available	O
+on	O
+some	O
+of	O
+the	O
+samples	O
+,	O
+the	O
+correlation	O
+between	O
+the	O
+IHC	O
+grading	O
+and	O
+the	O
+mRNA	O
+copy	O
+number	O
+was	O
+determined	O
+both	O
+in	O
+the	O
+original	O
+scale	O
+and	O
+in	O
+logarithmic	O
+transformations	O
+scale	O
+using	O
+S	O
+-	O
+PLUS	O
+software	O
+.	O
+
+Results	O
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+We	O
+have	O
+undertaken	O
+the	O
+current	O
+study	O
+to	O
+determine	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+breast	O
+cancer	O
+tissues	O
+that	O
+were	O
+positive	O
+and	O
+negative	O
+by	O
+two	O
+conventional	O
+methods	O
+of	O
+assaying	O
+ER	O
+alpha	O
+protein	O
+,	O
+IHC	O
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+estrogen	O
+binding	O
+.	O
+
+The	O
+rational	O
+for	O
+undertaking	O
+this	O
+study	O
+is	O
+that	O
+once	O
+we	O
+establish	O
+a	O
+threshold	O
+value	O
+in	O
+IHC	O
+negative	O
+tissues	O
+,	O
+then	O
+the	O
+molecular	O
+assay	O
+could	O
+be	O
+applied	O
+in	O
+clinical	O
+laboratories	O
+in	O
+the	O
+place	O
+of	O
+currently	O
+used	O
+IHC	O
+assay	O
+for	O
+determining	O
+the	O
+status	O
+of	O
+ER	O
+alpha	O
+for	O
+prognostic	O
+and	O
+therapeutic	O
+purposes	O
+.	O
+
+Our	O
+rational	O
+for	O
+establishing	O
+a	O
+cut	O
+off	O
+value	O
+is	O
+that	O
+any	O
+patient	B
+who	O
+expresses	O
+above	O
+the	O
+cut	O
+off	O
+level	O
+could	O
+be	O
+selected	O
+as	O
+a	O
+candidate	O
+for	O
+anti	O
+-	O
+estrogen	O
+therapies	O
+and	O
+could	O
+be	O
+considered	O
+to	O
+have	O
+good	O
+prognosis	O
+.	O
+
+We	O
+first	O
+profiled	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+70	O
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+IHC	O
+,	O
+43	O
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+assay	O
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+20	O
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+estrogen	O
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+.	O
+
+The	O
+data	O
+are	O
+presented	O
+in	O
+Tables	O
+1	O
+,	O
+3	O
+,	O
+2	O
+and	O
+4	O
+respectively	O
+.	O
+
+A	O
+box	O
+plot	O
+drawn	O
+for	O
+the	O
+copy	O
+numbers	O
+(	O
+logarithm	O
+base	O
+2	O
+scale	O
+)	O
+in	O
+the	O
+four	O
+groups	O
+(	O
+positive	O
+and	O
+negative	O
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+IHC	O
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+by	O
+estrogen	O
+binding	O
+assay	O
+)	O
+using	O
+S	O
+-	O
+PLUS	O
+software	O
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+shown	O
+in	O
+Figure	O
+1	O
+.	O
+
+We	O
+next	O
+compared	O
+the	O
+quantitative	O
+data	O
+on	O
+mRNA	O
+copy	O
+numbers	O
+among	O
+samples	O
+as	O
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+.	O
+
+1	O
+)	O
+We	O
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+whether	O
+the	O
+two	O
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+,	O
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+,	O
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+terms	O
+of	O
+mRNA	O
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+(	O
+Tables	O
+1	O
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+)	O
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+-	O
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+-	O
+sum	O
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+-	O
+sample	O
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+-	O
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+By	O
+these	O
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+,	O
+we	O
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+in	O
+the	O
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+alpha	O
+mRNA	O
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+numbers	O
+in	O
+samples	O
+that	O
+were	O
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+(	O
+p	O
+>	O
+0	O
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+28	O
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+)	O
+.	O
+
+2	O
+)	O
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+the	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+43	O
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+by	O
+IHC	O
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+20	O
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+by	O
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+binding	O
+assay	O
+and	O
+did	O
+not	O
+find	O
+significant	O
+differences	O
+(	O
+Tables	O
+3	O
+and	O
+4	O
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+)	O
+(	O
+p	O
+>	O
+0	O
+.	O
+25	O
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+.	O
+
+However	O
+,	O
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+)	O
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+found	O
+significant	O
+differences	O
+in	O
+mRNA	O
+copy	O
+numbers	O
+in	O
+the	O
+breast	O
+tumors	O
+that	O
+were	O
+IHC	O
+positive	O
+from	O
+those	O
+which	O
+were	O
+IHC	O
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+(	O
+Tables	O
+1	O
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+)	O
+(	O
+p	O
+=	O
+1	O
+.	O
+3e	O
+-	O
+6	O
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+standard	O
+two	O
+-	O
+sample	O
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+-	O
+test	O
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+p	O
+=	O
+2	O
+.	O
+7e	O
+-	O
+18	O
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+-	O
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+-	O
+sum	O
+test	O
+)	O
+.	O
+
+And	O
+4	O
+)	O
+we	O
+also	O
+found	O
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+differences	O
+in	O
+the	O
+samples	O
+that	O
+were	O
+positive	O
+and	O
+negative	O
+by	O
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+binding	O
+assay	O
+(	O
+Tables	O
+2	O
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+)	O
+(	O
+p	O
+=	O
+7	O
+.	O
+6e	O
+-	O
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+-	O
+sample	O
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+-	O
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+=	O
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+-	O
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+-	O
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+-	O
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+)	O
+.	O
+
+After	O
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+that	O
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+-	O
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+tissues	O
+express	O
+significantly	O
+higher	O
+levels	O
+of	O
+mRNA	O
+copy	O
+numbers	O
+compared	O
+to	O
+negative	O
+tumor	O
+samples	O
+,	O
+we	O
+next	O
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+the	O
+maximum	O
+level	O
+of	O
+expression	O
+in	O
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+-	O
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+program	O
+.	O
+
+By	O
+using	O
+this	O
+program	O
+,	O
+we	O
+found	O
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+maximum	O
+level	O
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+expression	O
+of	O
+mRNA	O
+copy	O
+numbers	O
+/	O
+cut	O
+-	O
+off	O
+value	O
+to	O
+be	O
+5	O
+x	O
+106	O
+per	O
+1010copies	O
+of	O
+GAPDH	O
+mRNA	O
+.	O
+
+Of	O
+the	O
+total	O
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+(	O
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+)	O
+samples	O
+in	O
+our	O
+study	O
+,	O
+83	O
+samples	O
+showed	O
+higher	O
+level	O
+of	O
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+than	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+copies	O
+of	O
+GAPDH	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+the	O
+samples	O
+that	O
+showed	O
+less	O
+than	O
+the	O
+above	O
+cut	O
+off	O
+value	O
+copy	O
+numbers	O
+could	O
+be	O
+due	O
+to	O
+false	O
+positivity	O
+by	O
+the	O
+above	O
+methods	O
+.	O
+
+In	O
+a	O
+total	O
+of	O
+63	O
+negative	O
+samples	O
+(	O
+43	O
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+)	O
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+showed	O
+higher	O
+expression	O
+than	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010GAPDH	O
+copies	O
+.	O
+
+It	O
+is	O
+also	O
+possible	O
+that	O
+the	O
+samples	O
+that	O
+showed	O
+higher	O
+than	O
+the	O
+cut	O
+off	O
+copy	O
+numbers	O
+could	O
+be	O
+false	O
+negative	O
+.	O
+
+The	O
+OR	O
+(	O
+Odds	O
+Ratio	O
+)	O
+in	O
+the	O
+two	O
+groups	O
+is	O
+about	O
+39	O
+.	O
+4	O
+,	O
+an	O
+extremely	O
+high	O
+OR	O
+value	O
+.	O
+
+The	O
+counts	O
+of	O
+the	O
+ER	O
+alpha	O
+-	O
+positive	O
+(	O
+80	O
+,	O
+23	O
+)	O
+and	O
+ER	O
+alpha	O
+-	O
+negative	O
+(	O
+6	O
+,	O
+66	O
+)	O
+in	O
+the	O
+two	O
+groups	O
+produce	O
+a	O
+chi	O
+-	O
+square	O
+value	O
+of	O
+88	O
+.	O
+2544	O
+with	O
+1	O
+degree	O
+of	O
+freedom	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+our	O
+T	O
+-	O
+test	O
+and	O
+Wilcoxon	O
+-	O
+rank	O
+-	O
+sum	O
+test	O
+results	O
+.	O
+
+We	O
+applied	O
+the	O
+above	O
+cut	O
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+value	O
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+the	O
+Sensitivity	O
+(	O
+percentage	O
+of	O
+samples	O
+that	O
+showed	O
+higher	O
+copy	O
+numbers	O
+than	O
+the	O
+cut	O
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+of	O
+5	O
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+106	O
+copies	O
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+1010	O
+GAPDH	O
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+)	O
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+Specificity	O
+(	O
+percentage	O
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+samples	O
+that	O
+showed	O
+less	O
+than	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+GAPDH	O
+copies	O
+in	O
+IHC	O
+negative	O
+tissues	O
+)	O
+and	O
+the	O
+values	O
+obtained	O
+were	O
+0	O
+.	O
+81	O
+and	O
+0	O
+.	O
+90	O
+respectively	O
+.	O
+
+We	O
+also	O
+determined	O
+Receiver	O
+Operating	O
+Characteristics	O
+using	O
+S	O
+-	O
+PLUS	O
+software	O
+and	O
+the	O
+ROC	O
+curve	O
+generated	O
+is	O
+shown	O
+in	O
+Figure	O
+2	O
+.	O
+
+The	O
+area	O
+under	O
+the	O
+ROC	O
+curve	O
+,	O
+0	O
+.	O
+89675	O
+,	O
+shows	O
+that	O
+the	O
+molecular	O
+assay	O
+clearly	O
+distinguishes	O
+the	O
+positives	O
+by	O
+IHC	O
+or	O
+estrogen	O
+binding	O
+from	O
+the	O
+negative	O
+tissues	O
+.	O
+
+Since	O
+we	O
+have	O
+the	O
+grading	O
+score	O
+as	O
+percent	O
+positive	O
+cells	O
+for	O
+about	O
+50	O
+samples	O
+(	O
+Table	O
+1	O
+)	O
+,	O
+we	O
+tested	O
+if	O
+a	O
+correlation	O
+exits	O
+between	O
+the	O
+percent	O
+positive	O
+cells	O
+by	O
+IHC	O
+and	O
+the	O
+mRNA	O
+copy	O
+numbers	O
+using	O
+S	O
+-	O
+PLUS	O
+software	O
+.	O
+
+We	O
+obtained	O
+a	O
+correlation	O
+coefficient	O
+of	O
+0	O
+.	O
+02	O
+.	O
+
+When	O
+we	O
+used	O
+the	O
+logarithmic	O
+transformations	O
+scale	O
+,	O
+we	O
+obtained	O
+a	O
+correlation	O
+coefficient	O
+of	O
+0	O
+.	O
+037	O
+.	O
+
+These	O
+results	O
+indicated	O
+that	O
+there	O
+is	O
+no	O
+correlation	O
+between	O
+the	O
+percent	O
+positive	O
+cells	O
+and	O
+the	O
+level	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+.	O
+
+These	O
+observations	O
+could	O
+be	O
+due	O
+to	O
+qualitative	O
+nature	O
+of	O
+IHC	O
+assay	O
+.	O
+
+The	O
+IHC	O
+data	O
+only	O
+show	O
+the	O
+number	O
+of	O
+positive	O
+cells	O
+but	O
+not	O
+quantitative	O
+to	O
+determine	O
+the	O
+level	O
+of	O
+ER	O
+alpha	O
+expression	O
+.	O
+
+The	O
+molecular	O
+assay	O
+based	O
+on	O
+RNA	O
+is	O
+quantitative	O
+to	O
+determine	O
+the	O
+level	O
+of	O
+ER	O
+alpha	O
+expression	O
+.	O
+
+Discussion	O
+and	O
+conclusion	O
+
+Previously	O
+ER	O
+alpha	O
+mRNA	O
+levels	O
+in	O
+immunohistochemicall	O
+positive	O
+and	O
+negative	O
+tissues	O
+were	O
+evaluated	O
+in	O
+breast	O
+cancer	O
+tissues	O
+by	O
+several	O
+groups	O
+using	O
+conventional	O
+RT	O
+PCR	O
+.	O
+
+Cullen	O
+et	O
+al	O
+[	O
+17	O
+]	O
+determined	O
+mRNA	O
+levels	O
+by	O
+conventional	O
+PCR	O
+in	O
+107	O
+breast	O
+cancer	O
+tissues	O
+.	O
+
+They	O
+reported	O
+that	O
+ER	O
+alpha	O
+mRNA	O
+was	O
+more	O
+frequently	O
+detected	O
+in	O
+ER	O
+alpha	O
+protein	O
+positive	O
+tissues	O
+than	O
+ER	O
+alpha	O
+protein	O
+negative	O
+tissues	O
+.	O
+
+Jarzabek	O
+et	O
+al	O
+[	O
+18	O
+]	O
+studied	O
+ER	O
+alpha	O
+mRNA	O
+levels	O
+and	O
+protein	O
+levels	O
+in	O
+41	O
+primary	O
+breast	O
+cancer	O
+tissues	O
+.	O
+
+They	O
+reported	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+in	O
+all	O
+the	O
+tissues	O
+,	O
+where	O
+as	O
+the	O
+protein	O
+was	O
+present	O
+only	O
+in	O
+70	O
+%	O
+of	O
+tumor	O
+tissues	O
+by	O
+Western	O
+blotting	O
+and	O
+67	O
+%	O
+showed	O
+positive	O
+by	O
+immunohistochemistry	O
+.	O
+
+They	O
+concluded	O
+that	O
+lack	O
+of	O
+ER	O
+alpha	O
+protein	O
+is	O
+not	O
+due	O
+to	O
+lack	O
+of	O
+ER	O
+alpha	O
+gene	O
+expression	O
+or	O
+methylation	O
+of	O
+its	O
+promoter	O
+,	O
+but	O
+may	O
+be	O
+due	O
+to	O
+post	O
+-	O
+transcriptional	O
+or	O
+post	O
+-	O
+translational	O
+mechanisms	O
+.	O
+
+Alkarain	O
+et	O
+al	O
+[	O
+19	O
+]	O
+reported	O
+the	O
+presence	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+in	O
+immunohistochemicall	O
+ER	O
+alpha	O
+-	O
+negative	O
+tissues	O
+.	O
+
+However	O
+,	O
+none	O
+of	O
+the	O
+above	O
+studies	O
+has	O
+evaluated	O
+the	O
+threshold	O
+levels	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+levels	O
+in	O
+immunohistochemicall	O
+negative	O
+tissues	O
+or	O
+those	O
+negative	O
+by	O
+ligand	O
+binding	O
+assays	O
+.	O
+
+Our	O
+quantitative	O
+analysis	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+copy	O
+numbers	O
+demonstrate	O
+that	O
+breast	O
+cancer	O
+tissues	O
+that	O
+are	O
+negative	O
+by	O
+both	O
+IHC	O
+and	O
+ligand	O
+binding	O
+express	O
+significant	O
+levels	O
+of	O
+ER	O
+alpha	O
+mRNA	O
+.	O
+
+The	O
+reasons	O
+why	O
+the	O
+mRNA	O
+is	O
+not	O
+translated	O
+to	O
+detectable	O
+protein	O
+are	O
+not	O
+clear	O
+.	O
+
+Our	O
+previous	O
+studies	O
+on	O
+ER	O
+beta	O
+mRNA	O
+copy	O
+numbers	O
+[	O
+9	O
+]	O
+in	O
+breast	O
+cancer	O
+tissues	O
+have	O
+shown	O
+that	O
+at	O
+the	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+mRNA	O
+copies	O
+of	O
+GAPDH	O
+levels	O
+ER	O
+beta	O
+protein	O
+is	O
+translated	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+either	O
+ER	O
+alpha	O
+mRNA	O
+is	O
+not	O
+translated	O
+or	O
+the	O
+translated	O
+protein	O
+is	O
+degraded	O
+to	O
+undetectable	O
+levels	O
+in	O
+these	O
+tissues	O
+.	O
+
+The	O
+results	O
+and	O
+the	O
+analysis	O
+presented	O
+above	O
+clearly	O
+demonstrate	O
+that	O
+the	O
+ER	O
+alpha	O
+positive	O
+tissues	O
+by	O
+IHC	O
+or	O
+estrogen	O
+binding	O
+assay	O
+express	O
+significantly	O
+higher	O
+mRNA	O
+copy	O
+numbers	O
+than	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+GAPDH	O
+copies	O
+.	O
+
+An	O
+extremely	O
+high	O
+Odds	O
+Ratio	O
+,	O
+high	O
+sensitivity	O
+and	O
+specificity	O
+demonstrate	O
+that	O
+the	O
+molecular	O
+assay	O
+could	O
+be	O
+used	O
+in	O
+the	O
+place	O
+of	O
+currently	O
+used	O
+IHC	O
+in	O
+the	O
+clinical	O
+laboratories	O
+.	O
+
+Based	O
+on	O
+our	O
+data	O
+above	O
+any	O
+patient	B
+who	O
+has	O
+more	O
+than	O
+5	O
+x	O
+106	O
+copies	O
+per	O
+1010	O
+GAPDH	O
+copies	O
+in	O
+her	O
+tumor	O
+tissue	O
+could	O
+be	O
+considered	O
+positive	O
+for	O
+ER	O
+alpha	O
+,	O
+could	O
+be	O
+selected	O
+for	O
+anti	O
+-	O
+estrogen	O
+therapies	O
+and	O
+considered	O
+to	O
+have	O
+good	O
+prognosis	O
+.	O
+
+However	O
+,	O
+the	O
+above	O
+described	O
+approach	O
+has	O
+some	O
+limitations	O
+in	O
+that	O
+it	O
+needs	O
+to	O
+be	O
+verified	O
+on	O
+a	O
+defined	O
+set	O
+of	O
+biopsy	O
+samples	O
+and	O
+with	O
+reference	O
+to	O
+another	O
+house	O
+keeping	O
+gene	O
+.	O
+
+Therefore	O
+,	O
+the	O
+results	O
+should	O
+be	O
+interpreted	O
+with	O
+caution	O
+and	O
+undoubtedly	O
+will	O
+require	O
+confirmation	O
+by	O
+a	O
+larger	O
+prospective	O
+multi	O
+-	O
+centered	O
+clinical	O
+study	O
+with	O
+a	O
+more	O
+accurate	O
+design	O
+to	O
+bring	O
+the	O
+technology	O
+to	O
+the	O
+clinic	O
+.	O
+
+The	O
+current	O
+study	O
+is	O
+a	O
+first	O
+step	O
+in	O
+that	O
+direction	O
+.	O
+
+We	O
+expect	O
+that	O
+the	O
+cost	O
+effective	O
+,	O
+extremely	O
+sensitive	O
+,	O
+high	O
+though	O
+-	O
+put	O
+molecular	O
+assay	O
+which	O
+requires	O
+only	O
+a	O
+few	O
+cancer	O
+cells	O
+could	O
+be	O
+an	O
+assay	O
+of	O
+choice	O
+to	O
+replace	O
+IHC	O
+in	O
+clinical	O
+labs	O
+for	O
+determining	O
+ER	O
+alpha	O
+status	O
+in	O
+breast	O
+cancer	O
+tissues	O
+once	O
+established	O
+in	O
+a	O
+multi	O
+-	O
+centered	O
+prospective	O
+clinical	O
+study	O
+.	O
+
+Abbreviations	O
+
+FAM	O
+,	O
+carboxy	O
+-	O
+fluorescein	O
+;	O
+TAMARA	O
+,	O
+6	O
+-	O
+carboxy	O
+tetraethyl	O
+-	O
+rhodamine	O
+;	O
+GAPDH	O
+,	O
+Glyceraldehyde	O
+-	O
+3	O
+phosphate	O
+dehydrogenase	O
+;	O
+ER	O
+alpha	O
+,	O
+estrogen	O
+receptor	O
+alpha	O
+;	O
+IHC	O
+,	O
+Immunohistochemistry	O
+;	O
+CART	O
+,	O
+Classification	O
+And	O
+Regression	O
+Tree	O
+;	O
+and	O
+OR	O
+,	O
+Odds	O
+Ratio	O
+and	O
+ROC	O
+,	O
+Receiver	O
+Operating	O
+Characteristics	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+I	O
+.	O
+
+P	O
+conceived	O
+the	O
+study	O
+,	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+,	O
+performed	O
+the	O
+real	O
+-	O
+time	O
+PCR	O
+quantifications	O
+of	O
+ERalph	O
+mRNA	O
+copy	O
+numbers	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+Q	O
+.	O
+Y	O
+participated	O
+in	O
+performing	O
+the	O
+statistical	O
+analysis	O
+of	O
+the	O
+data	O
+.	O
+
+Both	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+Molecular	O
+Basis	O
+for	O
+a	O
+Lack	O
+of	O
+Correlation	O
+between	O
+Viral	O
+Fitness	O
+and	O
+Cell	O
+Killing	O
+Capacity	O
+
+Abstract	O
+
+The	O
+relationship	O
+between	O
+parasite	O
+fitness	O
+and	O
+virulence	O
+has	O
+been	O
+the	O
+object	O
+of	O
+experimental	O
+and	O
+theoretical	O
+studies	O
+often	O
+with	O
+conflicting	O
+conclusions	O
+.	O
+
+Here	O
+,	O
+we	O
+provide	O
+direct	O
+experimental	O
+evidence	O
+that	O
+viral	O
+fitness	O
+and	O
+virulence	O
+,	O
+both	O
+measured	O
+in	O
+the	O
+same	O
+biological	O
+environment	O
+provided	O
+by	O
+host	O
+cells	O
+in	O
+culture	O
+,	O
+can	O
+be	O
+two	O
+unrelated	O
+traits	O
+.	O
+
+A	O
+biological	O
+clone	O
+of	O
+foot	B
+-	I
+and	I
+-	I
+mouth	I
+disease	I
+virus	I
+acquired	O
+high	O
+fitness	O
+and	O
+virulence	O
+(	O
+cell	O
+killing	O
+capacity	O
+)	O
+upon	O
+large	O
+population	O
+passages	O
+in	O
+cell	O
+culture	O
+.	O
+
+However	O
+,	O
+subsequent	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+resulted	O
+in	O
+profound	O
+fitness	O
+loss	O
+,	O
+but	O
+only	O
+a	O
+minimal	O
+decrease	O
+of	O
+virulence	O
+.	O
+
+While	O
+fitness	O
+-	O
+decreasing	O
+mutations	O
+have	O
+been	O
+mapped	O
+throughout	O
+the	O
+genome	O
+,	O
+virulence	O
+determinants	O
+-	O
+-	O
+studied	O
+here	O
+with	O
+mutant	O
+and	O
+chimeric	O
+viruses	O
+-	O
+-	O
+were	O
+multigenic	O
+,	O
+but	O
+concentrated	O
+on	O
+some	O
+genomic	O
+regions	O
+.	O
+
+Therefore	O
+,	O
+we	O
+propose	O
+a	O
+model	O
+in	O
+which	O
+viral	O
+virulence	O
+is	O
+more	O
+robust	O
+to	O
+mutation	O
+than	O
+viral	O
+fitness	O
+.	O
+
+As	O
+a	O
+consequence	O
+,	O
+depending	O
+on	O
+the	O
+passage	O
+regime	O
+,	O
+viral	O
+fitness	O
+and	O
+virulence	O
+can	O
+follow	O
+different	O
+evolutionary	O
+trajectories	O
+.	O
+
+This	O
+lack	O
+of	O
+correlation	O
+is	O
+relevant	O
+to	O
+current	O
+models	O
+of	O
+attenuation	O
+and	O
+virulence	O
+in	O
+that	O
+virus	O
+de	O
+-	O
+adaptation	O
+need	O
+not	O
+entail	O
+a	O
+decrease	O
+of	O
+virulence	O
+.	O
+
+Virulence	O
+expresses	O
+the	O
+harm	O
+that	O
+parasites	O
+inflict	O
+upon	O
+their	O
+hosts	O
+.	O
+
+Many	O
+studies	O
+have	O
+addressed	O
+the	O
+basis	O
+of	O
+virulence	O
+and	O
+its	O
+effect	O
+on	O
+host	O
+and	O
+parasite	O
+survival	O
+.	O
+
+It	O
+has	O
+generally	O
+been	O
+accepted	O
+that	O
+one	O
+of	O
+the	O
+components	O
+of	O
+parasite	O
+virulence	O
+is	O
+fitness	O
+,	O
+or	O
+the	O
+capacity	O
+of	O
+the	O
+parasite	O
+to	O
+multiply	O
+in	O
+its	O
+host	O
+.	O
+
+Some	O
+models	O
+have	O
+equated	O
+virulence	O
+with	O
+fitness	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+use	O
+foot	B
+-	I
+and	I
+-	I
+mouth	I
+disease	I
+virus	I
+(	O
+FMDV	B
+)	O
+to	O
+document	O
+that	O
+virulence	O
+and	O
+fitness	O
+-	O
+-	O
+measured	O
+in	O
+the	O
+same	O
+biological	O
+environment	O
+provided	O
+by	O
+cells	O
+in	O
+culture	O
+-	O
+-	O
+can	O
+be	O
+unrelated	O
+traits	O
+.	O
+
+This	O
+has	O
+been	O
+achieved	O
+by	O
+multiplying	O
+the	O
+virus	O
+in	O
+a	O
+manner	O
+that	O
+mutations	O
+accumulated	O
+in	O
+its	O
+genome	O
+.	O
+
+Mutations	O
+decreased	O
+fitness	O
+dramatically	O
+,	O
+but	O
+not	O
+virulence	O
+.	O
+
+Chimeric	O
+and	O
+mutant	O
+viruses	O
+were	O
+constructed	O
+to	O
+show	O
+that	O
+virulence	O
+is	O
+influenced	O
+by	O
+only	O
+some	O
+of	O
+the	O
+FMDV	B
+genes	O
+,	O
+while	O
+fitness	O
+is	O
+influenced	O
+by	O
+the	O
+entire	O
+genome	O
+.	O
+
+For	O
+this	O
+reason	O
+,	O
+virulence	O
+is	O
+more	O
+robust	O
+(	O
+"	O
+resistant	O
+"	O
+)	O
+than	O
+fitness	O
+to	O
+the	O
+effects	O
+of	O
+deleterious	O
+mutations	O
+.	O
+
+The	O
+fact	O
+that	O
+virulence	O
+can	O
+be	O
+unrelated	O
+to	O
+fitness	O
+has	O
+implications	O
+for	O
+the	O
+design	O
+of	O
+anti	O
+-	O
+viral	O
+vaccines	O
+because	O
+it	O
+suggests	O
+that	O
+it	O
+may	O
+be	O
+possible	O
+to	O
+design	O
+high	O
+fitness	O
+,	O
+low	O
+virulence	O
+strains	O
+to	O
+stimulate	O
+the	O
+host	O
+immune	O
+response	O
+.	O
+
+Furthermore	O
+,	O
+in	O
+modelling	O
+studies	O
+it	O
+cannot	O
+be	O
+assumed	O
+that	O
+virulence	O
+is	O
+equal	O
+to	O
+fitness	O
+.	O
+
+Introduction	O
+
+The	O
+relationship	O
+between	O
+fitness	O
+and	O
+virulence	O
+is	O
+an	O
+unsettled	O
+question	O
+,	O
+and	O
+sometimes	O
+fitness	O
+is	O
+considered	O
+a	O
+component	O
+of	O
+the	O
+virulence	O
+phenotype	O
+of	O
+parasites	O
+.	O
+
+RNA	O
+viruses	O
+are	O
+ideal	O
+systems	O
+to	O
+address	O
+this	O
+important	O
+question	O
+because	O
+of	O
+their	O
+high	O
+mutability	O
+and	O
+fecundity	O
+,	O
+which	O
+result	O
+in	O
+a	O
+potential	O
+for	O
+rapid	O
+evolution	O
+,	O
+and	O
+also	O
+because	O
+of	O
+the	O
+availability	O
+of	O
+quantitative	O
+fitness	O
+and	O
+virulence	O
+assays	O
+.	O
+
+RNA	O
+viruses	O
+replicate	O
+as	O
+complex	O
+and	O
+dynamic	O
+mutant	O
+spectra	O
+,	O
+termed	O
+viral	O
+quasispecies	O
+.	O
+
+Key	O
+to	O
+quasispecies	O
+dynamics	O
+are	O
+mutation	O
+rates	O
+in	O
+the	O
+range	O
+of	O
+10	O
+-	O
+3	O
+to	O
+10	O
+-	O
+5	O
+substitutions	O
+per	O
+nucleotide	O
+copied	O
+,	O
+and	O
+competition	O
+among	O
+continuously	O
+arising	O
+variant	O
+genomes	O
+[	O
+1	O
+-	O
+4	O
+]	O
+,	O
+which	O
+prompt	O
+rapid	O
+movements	O
+in	O
+sequence	O
+space	O
+,	O
+with	O
+corresponding	O
+changes	O
+of	O
+position	O
+in	O
+the	O
+fitness	O
+landscape	O
+[	O
+5	O
+]	O
+.	O
+
+Indeed	O
+,	O
+large	O
+population	O
+passages	O
+of	O
+RNA	O
+viruses	O
+in	O
+cell	O
+culture	O
+permit	O
+competitive	O
+optimization	O
+of	O
+mutant	O
+distributions	O
+that	O
+generally	O
+result	O
+in	O
+fitness	O
+gain	O
+[	O
+6	O
+,	O
+7	O
+]	O
+,	O
+while	O
+repeated	O
+bottleneck	O
+events	O
+(	O
+experimentally	O
+realized	O
+as	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+)	O
+lead	O
+to	O
+random	O
+accumulation	O
+of	O
+deleterious	O
+mutations	O
+(	O
+operation	O
+of	O
+Muller	O
+'	O
+s	O
+ratchet	O
+[	O
+8	O
+]	O
+)	O
+and	O
+result	O
+in	O
+average	O
+fitness	O
+decreases	O
+[	O
+9	O
+-	O
+13	O
+]	O
+.	O
+
+Fitness	O
+recovery	O
+of	O
+low	O
+fitness	O
+foot	B
+-	I
+and	I
+-	I
+mouth	I
+disease	I
+virus	I
+(	O
+FMDV	B
+)	O
+clones	O
+occurs	O
+mainly	O
+with	O
+introduction	O
+of	O
+mutations	O
+along	O
+the	O
+genome	O
+,	O
+with	O
+very	O
+few	O
+true	O
+reversions	O
+.	O
+
+An	O
+understanding	O
+of	O
+the	O
+consequences	O
+of	O
+fitness	O
+variation	O
+for	O
+viral	O
+virulence	O
+is	O
+a	O
+key	O
+question	O
+for	O
+viral	O
+pathogenesis	O
+and	O
+evolution	O
+.	O
+
+Here	O
+,	O
+we	O
+approach	O
+this	O
+issue	O
+with	O
+FMDV	B
+,	O
+an	O
+important	O
+viral	O
+pathogen	O
+in	O
+veterinary	O
+medicine	O
+[	O
+14	O
+]	O
+,	O
+and	O
+one	O
+that	O
+fully	O
+participates	O
+of	O
+quasispecies	O
+dynamics	O
+.	O
+
+Our	O
+laboratory	O
+has	O
+characterized	O
+multiple	O
+FMDV	B
+variants	O
+that	O
+derive	O
+from	O
+one	O
+original	O
+biological	O
+clone	O
+,	O
+and	O
+that	O
+occupy	O
+widely	O
+different	O
+fitness	O
+levels	O
+when	O
+replicating	O
+in	O
+a	O
+defined	O
+environment	O
+in	O
+cell	O
+culture	O
+.	O
+
+We	O
+define	O
+fitness	O
+as	O
+the	O
+replication	O
+capacity	O
+of	O
+a	O
+mutant	O
+FMDV	B
+,	O
+relative	O
+to	O
+a	O
+reference	O
+FMDV	B
+,	O
+in	O
+direct	O
+growth	O
+-	O
+competition	O
+upon	O
+coinfection	O
+of	O
+baby	O
+hamster	B
+kidney	O
+21	O
+(	O
+BHK	O
+-	O
+21	O
+)	O
+cells	O
+[	O
+15	O
+-	O
+17	O
+]	O
+.	O
+
+Fitness	O
+of	O
+FMDV	B
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+is	O
+a	O
+multigenic	O
+trait	O
+[	O
+7	O
+]	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+define	O
+virulence	O
+of	O
+FMDV	B
+as	O
+the	O
+capacity	O
+of	O
+the	O
+virus	O
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+under	O
+a	O
+standard	O
+set	O
+of	O
+cell	O
+culture	O
+conditions	O
+[	O
+18	O
+]	O
+.	O
+
+Thus	O
+,	O
+the	O
+FMDV	B
+-	O
+BHK	O
+-	O
+21	O
+system	O
+offered	O
+a	O
+means	O
+to	O
+investigate	O
+in	O
+a	O
+direct	O
+and	O
+comparative	O
+fashion	O
+the	O
+relationship	O
+between	O
+fitness	O
+and	O
+virulence	O
+of	O
+a	O
+virus	O
+,	O
+measured	O
+in	O
+the	O
+same	O
+biological	O
+environment	O
+provided	O
+by	O
+BHK	O
+-	O
+21	O
+cells	O
+.	O
+
+We	O
+describe	O
+the	O
+behavior	O
+of	O
+an	O
+FMDV	B
+clone	O
+(	O
+
+)	O
+,	O
+which	O
+has	O
+a	O
+history	O
+of	O
+repeated	O
+serial	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+[	O
+11	O
+]	O
+,	O
+that	O
+attained	O
+a	O
+very	O
+low	O
+fitness	O
+value	O
+relative	O
+to	O
+its	O
+parental	O
+reference	O
+virus	O
+(	O
+C	O
+-	O
+S8c1	O
+)	O
+,	O
+and	O
+yet	O
+,	O
+its	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+was	O
+significantly	O
+higher	O
+than	O
+that	O
+of	O
+C	O
+-	O
+S8c1	O
+.	O
+
+A	O
+comparative	O
+study	O
+of	O
+the	O
+capacity	O
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+of	O
+chimeric	O
+FMDVs	B
+constructed	O
+with	O
+cDNA	O
+copies	O
+of	O
+the	O
+two	O
+parental	O
+FMDVs	B
+indicates	O
+that	O
+the	O
+enhanced	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+of	O
+the	O
+low	O
+fitness	O
+clone	O
+is	O
+a	O
+polygenic	O
+trait	O
+,	O
+with	O
+participation	O
+of	O
+the	O
+regions	O
+encoding	O
+capsid	O
+proteins	O
+and	O
+non	O
+-	O
+structural	O
+proteins	O
+2A	O
+,	O
+2B	O
+,	O
+and	O
+2C	O
+as	O
+virulence	O
+determinants	O
+.	O
+
+Three	O
+specific	O
+amino	O
+acid	O
+replacements	O
+in	O
+2C	O
+have	O
+been	O
+identified	O
+as	O
+redundant	O
+virulence	O
+determinants	O
+of	O
+FMDV	B
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+.	O
+
+Thus	O
+,	O
+while	O
+large	O
+population	O
+passages	O
+of	O
+the	O
+virus	O
+resulted	O
+in	O
+a	O
+gain	O
+of	O
+both	O
+fitness	O
+and	O
+virulence	O
+,	O
+subsequent	O
+bottleneck	O
+passages	O
+resulted	O
+in	O
+a	O
+decrease	O
+of	O
+fitness	O
+but	O
+not	O
+of	O
+virulence	O
+.	O
+
+The	O
+results	O
+suggest	O
+that	O
+fitness	O
+is	O
+very	O
+vulnerable	O
+to	O
+mutation	O
+in	O
+any	O
+genomic	O
+region	O
+.	O
+
+In	O
+contrast	O
+,	O
+because	O
+of	O
+the	O
+involvement	O
+of	O
+several	O
+(	O
+but	O
+not	O
+all	O
+)	O
+viral	O
+genes	O
+in	O
+virulence	O
+,	O
+and	O
+the	O
+redundant	O
+effect	O
+of	O
+three	O
+2C	O
+substitutions	O
+,	O
+virulence	O
+is	O
+a	O
+more	O
+robust	O
+phenotypic	O
+trait	O
+than	O
+fitness	O
+,	O
+and	O
+less	O
+vulnerable	O
+to	O
+accumulation	O
+of	O
+mutations	O
+.	O
+
+Therefore	O
+,	O
+we	O
+provide	O
+direct	O
+evidence	O
+that	O
+viral	O
+fitness	O
+and	O
+capacity	O
+to	O
+kill	O
+cells	O
+can	O
+(	O
+in	O
+some	O
+cases	O
+)	O
+be	O
+unrelated	O
+traits	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+relationship	O
+between	O
+fitness	O
+and	O
+virulence	O
+,	O
+of	O
+being	O
+either	O
+linked	O
+or	O
+unrelated	O
+traits	O
+,	O
+depends	O
+on	O
+the	O
+evolutionary	O
+history	O
+of	O
+the	O
+virus	O
+.	O
+
+This	O
+observation	O
+has	O
+implications	O
+for	O
+viral	O
+pathogenesis	O
+,	O
+and	O
+sheds	O
+light	O
+on	O
+models	O
+of	O
+virulence	O
+proposed	O
+on	O
+the	O
+basis	O
+of	O
+theoretical	O
+and	O
+experimental	O
+studies	O
+with	O
+cellular	O
+organisms	O
+.	O
+
+Results	O
+
+Inability	O
+of	O
+FMDV	B
+
+to	O
+Establish	O
+a	O
+Persistent	O
+Infection	O
+in	O
+BHK	O
+-	O
+21	O
+Cells	O
+
+Several	O
+biological	O
+clones	O
+and	O
+populations	O
+were	O
+obtained	O
+by	O
+passaging	O
+FMDV	B
+biological	O
+clone	O
+C	O
+-	O
+S8c1	O
+[	O
+19	O
+-	O
+22	O
+]	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+either	O
+as	O
+large	O
+population	O
+passages	O
+or	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+The	O
+biological	O
+clones	O
+and	O
+populations	O
+differed	O
+up	O
+to	O
+236	O
+-	O
+fold	O
+in	O
+relative	O
+fitness	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+The	O
+fitness	O
+differences	O
+found	O
+are	O
+expected	O
+from	O
+previous	O
+results	O
+on	O
+fitness	O
+gain	O
+upon	O
+large	O
+population	O
+passages	O
+of	O
+RNA	O
+viruses	O
+[	O
+6	O
+,	O
+7	O
+]	O
+and	O
+fitness	O
+decrease	O
+upon	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+(	O
+bottleneck	O
+)	O
+transfers	O
+[	O
+9	O
+-	O
+13	O
+]	O
+.	O
+
+The	O
+initial	O
+experiment	O
+was	O
+aimed	O
+at	O
+testing	O
+whether	O
+
+,	O
+because	O
+of	O
+its	O
+low	O
+fitness	O
+(	O
+0	O
+.	O
+11	O
+times	O
+that	O
+of	O
+its	O
+parental	O
+C	O
+-	O
+S8c1	O
+[	O
+12	O
+,	O
+23	O
+,	O
+24	O
+]	O
+[	O
+Table	O
+1	O
+]	O
+)	O
+,	O
+had	O
+an	O
+advantage	O
+in	O
+establishing	O
+a	O
+persistent	O
+non	O
+-	O
+cytopathic	O
+infection	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+as	O
+compared	O
+with	O
+its	O
+parental	O
+clone	O
+,	O
+C	O
+-	O
+S8c1	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+A	O
+persistent	O
+FMDV	B
+infection	O
+is	O
+established	O
+by	O
+growing	O
+the	O
+cells	O
+that	O
+survive	O
+a	O
+standard	O
+cytolytic	O
+infection	O
+with	O
+FMDV	B
+[	O
+25	O
+]	O
+.	O
+
+Confluent	O
+monolayers	O
+of	O
+BHK	O
+-	O
+21	O
+cells	O
+were	O
+infected	O
+either	O
+with	O
+C	O
+-	O
+S8c1	O
+or	O
+with	O
+
+at	O
+a	O
+multiplicity	O
+of	O
+infection	O
+(	O
+MOI	O
+)	O
+of	O
+0	O
+.	O
+02	O
+-	O
+0	O
+.	O
+1	O
+plaque	O
+-	O
+forming	O
+units	O
+(	O
+PFU	O
+)	O
+/	O
+cell	O
+(	O
+2	O
+x	O
+106	O
+cells	O
+infected	O
+with	O
+4	O
+x	O
+104	O
+-	O
+2	O
+x	O
+105	O
+PFU	O
+)	O
+.	O
+
+Unexpectedly	O
+,	O
+at	O
+24	O
+h	O
+postinfection	O
+,	O
+the	O
+cells	O
+infected	O
+with	O
+
+showed	O
+extensive	O
+cytopathology	O
+,	O
+and	O
+at	O
+48	O
+h	O
+postinfection	O
+,	O
+no	O
+surviving	O
+cells	O
+were	O
+observed	O
+.	O
+
+The	O
+frequency	O
+of	O
+surviving	O
+cells	O
+in	O
+parallel	O
+infections	O
+with	O
+C	O
+-	O
+S8c1	O
+was	O
+5	O
+x	O
+10	O
+-	O
+3	O
+-	O
+9	O
+x	O
+10	O
+-	O
+3	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+previous	O
+determinations	O
+[	O
+25	O
+]	O
+.	O
+
+No	O
+persistently	O
+infected	O
+BHK	O
+-	O
+21	O
+cell	O
+cultures	O
+could	O
+be	O
+established	O
+with	O
+
+,	O
+despite	O
+several	O
+attempts	O
+.	O
+
+Thus	O
+,	O
+C	O
+-	O
+S8c1	O
+,	O
+which	O
+displays	O
+a	O
+9	O
+-	O
+fold	O
+higher	O
+relative	O
+fitness	O
+than	O
+
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+showed	O
+a	O
+capacity	O
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+that	O
+was	O
+at	O
+least	O
+103	O
+-	O
+fold	O
+lower	O
+than	O
+the	O
+killing	O
+capacity	O
+of	O
+
+in	O
+the	O
+infectivity	O
+assay	O
+intended	O
+to	O
+establish	O
+a	O
+persistent	O
+FMDV	B
+infection	O
+.	O
+
+FMDV	B
+Fitness	O
+and	O
+Capacity	O
+to	O
+Kill	O
+BHK	O
+-	O
+21	O
+Cells	O
+May	O
+Not	O
+Be	O
+Positively	O
+Correlated	O
+
+The	O
+capacity	O
+of	O
+
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+despite	O
+its	O
+low	O
+fitness	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+led	O
+us	O
+to	O
+quantitatively	O
+examine	O
+the	O
+relationship	O
+between	O
+fitness	O
+of	O
+FMDV	B
+and	O
+its	O
+capacity	O
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+.	O
+
+To	O
+this	O
+aim	O
+,	O
+FMDV	B
+clones	O
+or	O
+populations	O
+were	O
+compared	O
+in	O
+a	O
+cell	O
+killing	O
+assay	O
+,	O
+consisting	O
+in	O
+determining	O
+the	O
+time	O
+required	O
+to	O
+kill	O
+104	O
+BHK	O
+-	O
+21	O
+cells	O
+as	O
+a	O
+function	O
+of	O
+the	O
+PFU	O
+added	O
+(	O
+described	O
+in	O
+Materials	O
+and	O
+Methods	O
+)	O
+.	O
+
+The	O
+results	O
+(	O
+Figure	O
+2A	O
+)	O
+indicate	O
+that	O
+over	O
+the	O
+time	O
+range	O
+of	O
+12	O
+h	O
+to	O
+48	O
+h	O
+postinfection	O
+,	O
+the	O
+number	O
+of	O
+PFUs	O
+needed	O
+to	O
+kill	O
+104	O
+BHK	O
+-	O
+21	O
+cells	O
+varied	O
+logarithmically	O
+as	O
+a	O
+function	O
+of	O
+time	O
+.	O
+
+Similar	O
+quantifications	O
+of	O
+relative	O
+virulence	O
+were	O
+obtained	O
+by	O
+measuring	O
+the	O
+PFU	O
+needed	O
+to	O
+kill	O
+104	O
+cells	O
+in	O
+24	O
+h	O
+,	O
+and	O
+then	O
+by	O
+extrapolating	O
+the	O
+PFU	O
+values	O
+to	O
+0	O
+h	O
+postinfection	O
+(	O
+Tables	O
+1	O
+and	O
+S1	O
+)	O
+.	O
+
+Virulence	O
+of	O
+
+was	O
+29	O
+to	O
+35	O
+times	O
+higher	O
+than	O
+virulence	O
+of	O
+C	O
+-	O
+S8c1	O
+,	O
+despite	O
+the	O
+latter	O
+displaying	O
+a	O
+9	O
+-	O
+fold	O
+higher	O
+fitness	O
+(	O
+Tables	O
+1	O
+and	O
+S1	O
+)	O
+.	O
+
+The	O
+high	O
+virulence	O
+of	O
+
+was	O
+not	O
+due	O
+to	O
+the	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+,	O
+since	O
+a	O
+high	O
+virulence	O
+was	O
+also	O
+quantitated	O
+for	O
+its	O
+parental	O
+clone	O
+,	O
+
+,	O
+and	O
+for	O
+population	O
+C	O
+-	O
+S8p113	O
+(	O
+Figure	O
+2B	O
+;	O
+Tables	O
+1	O
+,	O
+2	O
+,	O
+and	O
+S1	O
+)	O
+.	O
+
+deviated	O
+from	O
+a	O
+line	O
+that	O
+correlated	O
+relative	O
+fitness	O
+of	O
+FMDV	B
+and	O
+the	O
+logarithm	O
+of	O
+cell	O
+killing	O
+capacity	O
+,	O
+as	O
+reflected	O
+in	O
+the	O
+decrease	O
+of	O
+the	O
+regression	O
+coefficient	O
+(	O
+R2	O
+)	O
+(	O
+inset	O
+in	O
+Figure	O
+2A	O
+)	O
+.	O
+
+Probably	O
+,	O
+this	O
+deviation	O
+is	O
+due	O
+to	O
+the	O
+fact	O
+that	O
+
+lost	O
+fitness	O
+due	O
+to	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+,	O
+and	O
+the	O
+other	O
+viruses	O
+were	O
+not	O
+subjected	O
+to	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+virulence	O
+determinants	O
+were	O
+acquired	O
+during	O
+the	O
+large	O
+population	O
+passages	O
+done	O
+between	O
+C	O
+-	O
+S8c1	O
+and	O
+C	O
+-	O
+S8c1p113	O
+.	O
+
+The	O
+29	O
+-	O
+to	O
+35	O
+-	O
+fold	O
+higher	O
+virulence	O
+of	O
+
+with	O
+respect	O
+to	O
+C	O
+-	O
+S8c1	O
+(	O
+Tables	O
+1	O
+and	O
+S1	O
+)	O
+,	O
+despite	O
+its	O
+low	O
+fitness	O
+,	O
+indicates	O
+that	O
+viral	O
+fitness	O
+and	O
+virulence	O
+can	O
+be	O
+two	O
+unrelated	O
+traits	O
+.	O
+
+Mapping	O
+Virulence	O
+Determinants	O
+in	O
+the	O
+
+Genome	O
+
+The	O
+comparison	O
+of	O
+the	O
+consensus	O
+nucleotide	O
+sequence	O
+of	O
+the	O
+
+genome	O
+with	O
+that	O
+of	O
+C	O
+-	O
+S8c1	O
+revealed	O
+a	O
+total	O
+of	O
+47	O
+mutations	O
+(	O
+Table	O
+S2	O
+)	O
+,	O
+leading	O
+to	O
+21	O
+amino	O
+acid	O
+replacements	O
+affecting	O
+structural	O
+and	O
+non	O
+-	O
+structural	O
+proteins	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+To	O
+identify	O
+the	O
+genomic	O
+regions	O
+associated	O
+with	O
+the	O
+increased	O
+virulence	O
+of	O
+
+with	O
+respect	O
+to	O
+C	O
+-	O
+S8c1	O
+,	O
+we	O
+measured	O
+the	O
+BHK	O
+-	O
+21	O
+cell	O
+killing	O
+capacity	O
+of	O
+nine	O
+chimeric	O
+viruses	O
+rescued	O
+from	O
+constructs	O
+obtained	O
+by	O
+introducing	O
+fragments	O
+of	O
+cDNA	O
+of	O
+the	O
+
+genome	O
+into	O
+plasmid	O
+pMT28	O
+,	O
+which	O
+encodes	O
+infectious	O
+C	O
+-	O
+S8c1	O
+RNA	O
+[	O
+21	O
+]	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+The	O
+results	O
+(	O
+Figure	O
+5	O
+;	O
+Tables	O
+2	O
+and	O
+S1	O
+)	O
+show	O
+that	O
+several	O
+genomic	O
+regions	O
+contribute	O
+to	O
+the	O
+virulence	O
+of	O
+
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+and	O
+that	O
+the	O
+major	O
+contributors	O
+map	O
+within	O
+genomic	O
+positions	O
+2046	O
+to	O
+3760	O
+(	O
+residues	O
+encoding	O
+part	O
+of	O
+VP2	O
+,	O
+VP3	O
+,	O
+and	O
+part	O
+of	O
+VP1	O
+,	O
+Figure	O
+5A	O
+)	O
+and	O
+3760	O
+to	O
+5839	O
+(	O
+residues	O
+encoding	O
+2A	O
+,	O
+2B	O
+,	O
+2C	O
+,	O
+and	O
+3A	O
+,	O
+Figure	O
+5B	O
+)	O
+.	O
+
+The	O
+results	O
+exclude	O
+the	O
+internal	O
+ribosome	O
+entry	O
+site	O
+and	O
+the	O
+3C	O
+-	O
+and	O
+3D	O
+-	O
+coding	O
+regions	O
+as	O
+significant	O
+virulence	O
+determinants	O
+of	O
+
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+(	O
+virulence	O
+of	O
+the	O
+relevant	O
+chimeric	O
+viruses	O
+<	O
+=	O
+2	O
+.	O
+5	O
+,	O
+relative	O
+to	O
+C	O
+-	O
+S8c1	O
+;	O
+Tables	O
+2	O
+and	O
+S1	O
+)	O
+.	O
+
+Infectious	O
+progeny	O
+production	O
+by	O
+each	O
+chimeric	O
+virus	O
+was	O
+intermediate	O
+between	O
+the	O
+production	O
+of	O
+the	O
+parental	O
+viruses	O
+pMT28	O
+and	O
+
+,	O
+with	O
+no	O
+significant	O
+differences	O
+that	O
+could	O
+be	O
+correlated	O
+with	O
+virulence	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Non	O
+-	O
+Structural	O
+Protein	O
+2C	O
+Is	O
+a	O
+Determinant	O
+of	O
+the	O
+Virulence	O
+of	O
+FMDV	B
+for	O
+BHK	O
+-	O
+21	O
+Cells	O
+
+Amino	O
+acid	O
+substitutions	O
+in	O
+human	B
+rhinovirus	I
+protein	O
+2C	O
+promoted	O
+cytopathology	O
+for	O
+mouse	B
+L	O
+cells	O
+[	O
+26	O
+]	O
+.	O
+
+Remarkably	O
+,	O
+
+shares	O
+with	O
+other	O
+FMDV	B
+clones	O
+and	O
+populations	O
+,	O
+notably	O
+,	O
+MARLS	O
+and	O
+C	O
+-	O
+S8p260p3d	O
+(	O
+the	O
+two	O
+viruses	O
+showing	O
+the	O
+highest	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+;	O
+Figure	O
+2A	O
+;	O
+Tables	O
+1	O
+and	O
+S1	O
+)	O
+,	O
+three	O
+amino	O
+acid	O
+substitutions	O
+in	O
+2C	O
+:	O
+S80N	O
+,	O
+T256A	O
+,	O
+and	O
+Q263H	O
+.	O
+
+In	O
+addition	O
+,	O
+MARLS	O
+and	O
+CS8p260p3d	O
+include	O
+replacement	O
+M283V	O
+in	O
+2C	O
+,	O
+relative	O
+to	O
+C	O
+-	O
+S8c1	O
+[	O
+27	O
+,	O
+28	O
+]	O
+.	O
+
+To	O
+test	O
+whether	O
+any	O
+(	O
+or	O
+a	O
+combination	O
+)	O
+of	O
+the	O
+three	O
+shared	O
+amino	O
+acid	O
+substitutions	O
+in	O
+2C	O
+contributed	O
+to	O
+the	O
+increased	O
+virulence	O
+of	O
+FMDV	B
+,	O
+each	O
+of	O
+the	O
+mutations	O
+was	O
+introduced	O
+individually	O
+into	O
+plasmid	O
+pMT28	O
+by	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+,	O
+as	O
+described	O
+in	O
+Materials	O
+and	O
+Methods	O
+.	O
+
+Transcripts	O
+of	O
+the	O
+three	O
+mutants	O
+,	O
+termed	O
+pMT28	O
+(	O
+SN	O
+)	O
+,	O
+pMT28	O
+(	O
+TA	O
+)	O
+,	O
+and	O
+pMT28	O
+(	O
+QH	O
+)	O
+(	O
+Figure	O
+4	O
+)	O
+,	O
+were	O
+used	O
+to	O
+transfect	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+and	O
+the	O
+viruses	O
+obtained	O
+were	O
+tested	O
+with	O
+the	O
+BHK	O
+-	O
+21	O
+cell	O
+killing	O
+assay	O
+.	O
+
+Viruses	O
+having	O
+any	O
+of	O
+the	O
+substitutions	O
+in	O
+2C	O
+have	O
+a	O
+virulence	O
+intermediate	O
+between	O
+that	O
+of	O
+C	O
+-	O
+S8c1	O
+and	O
+
+(	O
+Figure	O
+6A	O
+)	O
+.	O
+
+To	O
+test	O
+whether	O
+the	O
+combination	O
+of	O
+the	O
+three	O
+substitutions	O
+in	O
+2C	O
+could	O
+produce	O
+an	O
+additional	O
+increase	O
+of	O
+virulence	O
+,	O
+the	O
+three	O
+mutations	O
+were	O
+introduced	O
+in	O
+pMT28	O
+to	O
+rescue	O
+the	O
+triple	O
+mutant	O
+pMT28	O
+(	O
+SN	O
+,	O
+TA	O
+,	O
+QH	O
+)	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+The	O
+results	O
+(	O
+Figure	O
+6B	O
+)	O
+show	O
+that	O
+the	O
+virulence	O
+of	O
+the	O
+triple	O
+2C	O
+mutant	O
+is	O
+similar	O
+to	O
+the	O
+virulence	O
+of	O
+the	O
+individual	O
+2C	O
+mutants	O
+.	O
+
+The	O
+2C	O
+mutations	O
+did	O
+not	O
+significantly	O
+affect	O
+the	O
+infectious	O
+progeny	O
+production	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+A	O
+testable	O
+prediction	O
+of	O
+this	O
+result	O
+is	O
+that	O
+the	O
+introduction	O
+of	O
+the	O
+wild	O
+-	O
+type	O
+2C	O
+-	O
+3A	O
+-	O
+coding	O
+region	O
+in	O
+the	O
+genetic	O
+background	O
+of	O
+
+should	O
+produce	O
+a	O
+virus	O
+with	O
+lower	O
+virulence	O
+than	O
+
+.	O
+Indeed	O
+,	O
+the	O
+results	O
+with	O
+such	O
+a	O
+chimeric	O
+virus	O
+(	O
+Figure	O
+5D	O
+)	O
+indicate	O
+that	O
+the	O
+presence	O
+of	O
+the	O
+2C	O
+-	O
+and	O
+3A	O
+-	O
+coding	O
+region	O
+as	O
+the	O
+only	O
+genetic	O
+region	O
+of	O
+the	O
+pMT28	O
+in	O
+the	O
+genetic	O
+background	O
+of	O
+
+resulted	O
+in	O
+an	O
+FMDV	B
+with	O
+a	O
+2	O
+.	O
+4	O
+-	O
+to	O
+4	O
+.	O
+8	O
+-	O
+fold	O
+lower	O
+virulence	O
+than	O
+
+.	O
+We	O
+conclude	O
+that	O
+mutations	O
+in	O
+2C	O
+contribute	O
+to	O
+virulence	O
+of	O
+FMDV	B
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+.	O
+
+Thus	O
+,	O
+a	O
+virus	O
+that	O
+evolves	O
+towards	O
+low	O
+fitness	O
+levels	O
+due	O
+to	O
+the	O
+operation	O
+of	O
+Muller	O
+'	O
+s	O
+ratchet	O
+may	O
+nevertheless	O
+maintain	O
+its	O
+capacity	O
+to	O
+kill	O
+the	O
+same	O
+cells	O
+in	O
+which	O
+it	O
+displays	O
+low	O
+fitness	O
+.	O
+
+In	O
+FMDV	B
+,	O
+the	O
+enhanced	O
+capacity	O
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+was	O
+multigenic	O
+,	O
+including	O
+participation	O
+of	O
+non	O
+-	O
+structural	O
+protein	O
+2C	O
+with	O
+three	O
+amino	O
+acid	O
+substitutions	O
+acting	O
+in	O
+a	O
+redundant	O
+fashion	O
+.	O
+
+In	O
+conclusion	O
+,	O
+the	O
+results	O
+provide	O
+a	O
+molecular	O
+interpretation	O
+of	O
+why	O
+fitness	O
+and	O
+virulence	O
+of	O
+an	O
+animal	O
+virus	O
+can	O
+follow	O
+disparate	O
+evolutionary	O
+trajectories	O
+,	O
+culminating	O
+in	O
+two	O
+unrelated	O
+traits	O
+.	O
+
+Discussion	O
+
+The	O
+capacity	O
+of	O
+a	O
+virus	O
+to	O
+kill	O
+cells	O
+is	O
+probably	O
+influenced	O
+by	O
+several	O
+steps	O
+in	O
+the	O
+virus	O
+life	O
+cycle	O
+,	O
+including	O
+receptor	O
+affinity	O
+(	O
+which	O
+may	O
+trigger	O
+signalling	O
+pathways	O
+and	O
+alter	O
+cell	O
+functions	O
+)	O
+and	O
+intracellular	O
+viral	O
+replication	O
+that	O
+may	O
+lead	O
+to	O
+metabolic	O
+alterations	O
+such	O
+as	O
+transcriptional	O
+or	O
+translational	O
+shut	O
+-	O
+off	O
+[	O
+29	O
+]	O
+.	O
+
+A	O
+parallel	O
+increase	O
+of	O
+virulence	O
+and	O
+fitness	O
+as	O
+a	O
+virus	O
+improves	O
+its	O
+adaptation	O
+to	O
+a	O
+host	O
+cell	O
+type	O
+is	O
+expected	O
+,	O
+since	O
+a	O
+key	O
+parameter	O
+that	O
+should	O
+contribute	O
+to	O
+the	O
+fitness	O
+level	O
+of	O
+a	O
+cytophatic	O
+virus	O
+is	O
+the	O
+accumulation	O
+of	O
+infectious	O
+particles	O
+and	O
+its	O
+release	O
+from	O
+cells	O
+,	O
+which	O
+are	O
+events	O
+often	O
+associated	O
+with	O
+cell	O
+killing	O
+.	O
+
+This	O
+expectation	O
+was	O
+fulfilled	O
+in	O
+our	O
+experiments	O
+(	O
+increase	O
+of	O
+both	O
+fitness	O
+and	O
+cell	O
+killing	O
+following	O
+large	O
+population	O
+passages	O
+of	O
+C	O
+-	O
+S8c1	O
+[	O
+Figure	O
+2	O
+]	O
+)	O
+,	O
+and	O
+also	O
+in	O
+other	O
+virus	O
+-	O
+host	O
+systems	O
+.	O
+
+In	O
+a	O
+comparison	O
+of	O
+two	O
+genetically	O
+divergent	O
+isolates	O
+of	O
+the	O
+whispovirus	O
+white	O
+spot	O
+syndrome	O
+virus	O
+,	O
+whose	O
+virulence	O
+for	O
+the	O
+shrimp	B
+host	O
+Penaeus	B
+monodon	I
+was	O
+measured	O
+by	O
+in	O
+vivo	O
+cumulative	O
+mortality	O
+rates	O
+,	O
+virulence	O
+correlated	O
+with	O
+competitive	O
+fitness	O
+in	O
+vivo	O
+[	O
+30	O
+]	O
+.	O
+
+The	O
+onset	O
+of	O
+type	O
+1	O
+diabetes	O
+by	O
+coxsackievirus	O
+B	O
+strains	O
+was	O
+linked	O
+to	O
+the	O
+viral	O
+replication	O
+rate	O
+and	O
+to	O
+the	O
+infectious	O
+dose	O
+[	O
+31	O
+]	O
+.	O
+
+In	O
+engineered	O
+alphavirus	O
+replicons	O
+,	O
+a	O
+direct	O
+correlation	O
+between	O
+the	O
+level	O
+of	O
+RNA	O
+replication	O
+and	O
+cytopathogenicity	O
+was	O
+observed	O
+[	O
+32	O
+]	O
+.	O
+
+At	O
+an	O
+epidemiological	O
+level	O
+,	O
+a	O
+greater	O
+replicative	O
+fitness	O
+of	O
+historical	O
+versus	O
+current	O
+human	B
+immunodeficiency	I
+virus	I
+type	I
+1	I
+(	O
+HIV	B
+-	I
+1	I
+)	O
+isolates	O
+was	O
+taken	O
+as	O
+evidence	O
+of	O
+HIV	B
+-	I
+1	I
+attenuation	O
+over	O
+time	O
+,	O
+assuming	O
+a	O
+direct	O
+connection	O
+between	O
+fitness	O
+and	O
+virulence	O
+[	O
+33	O
+]	O
+.	O
+
+In	O
+vivo	O
+,	O
+viral	O
+fitness	O
+may	O
+vary	O
+among	O
+specific	O
+organs	O
+,	O
+and	O
+virulence	O
+may	O
+be	O
+affected	O
+only	O
+when	O
+fitness	O
+for	O
+some	O
+specific	O
+target	O
+tissues	O
+is	O
+affected	O
+[	O
+34	O
+]	O
+.	O
+
+Replicative	O
+fitness	O
+is	O
+,	O
+however	O
+,	O
+but	O
+one	O
+of	O
+several	O
+factors	O
+which	O
+influence	O
+the	O
+progression	O
+of	O
+a	O
+viral	O
+infection	O
+in	O
+vivo	O
+.	O
+
+In	O
+a	O
+comparative	O
+analysis	O
+,	O
+R5	O
+-	O
+tropic	O
+and	O
+X4	O
+-	O
+tropic	O
+clones	O
+of	O
+HIV	B
+-	I
+1	I
+showed	O
+similar	O
+replication	O
+capacity	O
+in	O
+mitogen	O
+-	O
+activated	O
+T	O
+cells	O
+.	O
+
+However	O
+,	O
+X4	O
+clones	O
+were	O
+transferred	O
+more	O
+efficiently	O
+than	O
+R5	O
+clones	O
+from	O
+dendritic	O
+cells	O
+to	O
+CD4	O
+(	O
++	O
+)	O
+T	O
+cells	O
+,	O
+a	O
+fact	O
+that	O
+can	O
+contribute	O
+to	O
+the	O
+competitive	O
+advantage	O
+of	O
+X4	O
+viruses	O
+in	O
+AIDS	O
+patients	B
+[	O
+35	O
+]	O
+.	O
+
+Simian	B
+immunodeficiency	I
+virus	I
+SIVmac239	B
+infects	O
+both	O
+the	O
+sooty	B
+mangabey	I
+and	O
+the	O
+rhesus	B
+macaque	I
+,	O
+reaching	O
+high	O
+viral	O
+loads	O
+in	O
+both	O
+hosts	O
+,	O
+yet	O
+it	O
+is	O
+only	O
+virulent	O
+for	O
+the	O
+rhesus	B
+macaque	I
+[	O
+36	O
+]	O
+.	O
+
+Deviations	O
+of	O
+a	O
+positive	O
+correlation	O
+between	O
+viral	O
+fitness	O
+and	O
+virulence	O
+were	O
+observed	O
+also	O
+in	O
+the	O
+plant	O
+viruses	O
+cucumber	B
+mosaic	I
+virus	I
+[	O
+37	O
+]	O
+and	O
+barley	B
+stripe	I
+mosaic	I
+virus	I
+[	O
+38	O
+]	O
+.	O
+
+A	O
+study	O
+of	O
+the	O
+effect	O
+of	O
+lysis	O
+timing	O
+on	O
+bacteriophage	B
+fitness	O
+revealed	O
+that	O
+a	O
+strain	O
+with	O
+an	O
+intermediate	O
+lysis	O
+time	O
+had	O
+the	O
+highest	O
+fitness	O
+[	O
+39	O
+]	O
+.	O
+
+The	O
+time	O
+of	O
+transmission	O
+may	O
+also	O
+affect	O
+virulence	O
+.	O
+
+Nuclear	O
+polyhedrosis	O
+virus	O
+transmitted	O
+early	O
+to	O
+its	O
+host	O
+,	O
+the	O
+moth	O
+Lymantria	B
+dispar	I
+,	O
+was	O
+more	O
+virulent	O
+than	O
+virus	O
+transmitted	O
+late	O
+,	O
+although	O
+the	O
+latter	O
+was	O
+more	O
+productive	O
+because	O
+the	O
+virus	O
+could	O
+use	O
+more	O
+host	O
+tissue	O
+for	O
+replication	O
+[	O
+40	O
+]	O
+.	O
+
+In	O
+a	O
+study	O
+of	O
+the	O
+susceptibility	O
+of	O
+North	O
+American	O
+and	O
+non	O
+-	O
+North	O
+American	O
+breeds	O
+of	O
+Lymantria	O
+to	O
+several	O
+isolates	O
+of	O
+the	O
+fungus	O
+Entomaphaga	B
+maimaiga	I
+,	O
+mortality	O
+was	O
+scored	O
+in	O
+all	O
+cases	O
+.	O
+
+However	O
+,	O
+virulence	O
+of	O
+the	O
+fungus	O
+,	O
+quantitated	O
+by	O
+the	O
+time	O
+of	O
+death	O
+of	O
+Lymantria	O
+,	O
+was	O
+,	O
+in	O
+some	O
+cases	O
+,	O
+inversely	O
+proportional	O
+to	O
+fitness	O
+,	O
+quantitated	O
+by	O
+fungal	O
+reproduction	O
+in	O
+the	O
+moth	B
+[	O
+41	O
+]	O
+.	O
+
+In	O
+all	O
+these	O
+cases	O
+,	O
+the	O
+molecular	O
+basis	O
+of	O
+the	O
+lack	O
+of	O
+positive	O
+correlation	O
+between	O
+fitness	O
+and	O
+virulence	O
+is	O
+not	O
+understood	O
+.	O
+
+Model	O
+for	O
+a	O
+Lack	O
+of	O
+Correlation	O
+between	O
+Viral	O
+Fitness	O
+and	O
+Virulence	O
+
+The	O
+results	O
+with	O
+FMDV	B
+clones	O
+H5	O
+have	O
+documented	O
+that	O
+both	O
+fitness	O
+-	O
+enhancing	O
+and	O
+virulence	O
+-	O
+enhancing	O
+mutations	O
+can	O
+be	O
+incorporated	O
+in	O
+the	O
+viral	O
+genome	O
+in	O
+such	O
+a	O
+fashion	O
+that	O
+subsequent	O
+fitness	O
+-	O
+decreasing	O
+mutations	O
+associated	O
+with	O
+bottleneck	O
+(	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+)	O
+transfers	O
+produce	O
+only	O
+minimal	O
+effects	O
+on	O
+virulence	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+The	O
+dissection	O
+of	O
+accompanying	O
+molecular	O
+events	O
+,	O
+achieved	O
+through	O
+quantification	O
+of	O
+virulence	O
+of	O
+recombinant	O
+and	O
+mutant	O
+genomes	O
+(	O
+Tables	O
+2	O
+and	O
+S1	O
+)	O
+,	O
+provides	O
+an	O
+interpretation	O
+of	O
+the	O
+lack	O
+of	O
+positive	O
+correlation	O
+between	O
+virulence	O
+and	O
+fitness	O
+.	O
+
+Multiple	O
+fitness	O
+-	O
+decreasing	O
+mutations	O
+occur	O
+in	O
+the	O
+course	O
+of	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+,	O
+distributed	O
+throughout	O
+the	O
+FMDV	B
+genome	O
+[	O
+11	O
+]	O
+.	O
+
+In	O
+contrast	O
+,	O
+determinants	O
+of	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+are	O
+multigenic	O
+,	O
+but	O
+concentrated	O
+mainly	O
+in	O
+some	O
+FMDV	B
+genomic	O
+regions	O
+.	O
+
+Similar	O
+multigenic	O
+but	O
+discrete	O
+virulence	O
+determinants	O
+have	O
+been	O
+described	O
+also	O
+in	O
+other	O
+virus	O
+-	O
+host	O
+systems	O
+[	O
+42	O
+,	O
+43	O
+]	O
+.	O
+
+To	O
+decrease	O
+virulence	O
+,	O
+mutations	O
+occurring	O
+randomly	O
+in	O
+the	O
+course	O
+of	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+should	O
+affect	O
+specific	O
+genomic	O
+sites	O
+,	O
+and	O
+this	O
+will	O
+occur	O
+with	O
+a	O
+lower	O
+probability	O
+than	O
+fitness	O
+-	O
+decreasing	O
+mutations	O
+,	O
+which	O
+can	O
+hit	O
+any	O
+of	O
+the	O
+multifunctional	O
+picornaviral	O
+proteins	O
+and	O
+regulatory	O
+regions	O
+[	O
+11	O
+]	O
+.	O
+
+This	O
+model	O
+is	O
+reinforced	O
+by	O
+the	O
+observation	O
+that	O
+three	O
+amino	O
+acid	O
+substitutions	O
+in	O
+2C	O
+(	O
+S80N	O
+,	O
+T256A	O
+,	O
+and	O
+Q263H	O
+)	O
+had	O
+a	O
+similar	O
+effect	O
+in	O
+enhancing	O
+FMDV	B
+virulence	O
+,	O
+and	O
+the	O
+three	O
+mutations	O
+in	O
+the	O
+same	O
+genome	O
+had	O
+an	O
+effect	O
+comparable	O
+to	O
+each	O
+mutation	O
+individually	O
+(	O
+Figure	O
+6	O
+;	O
+Tables	O
+2	O
+and	O
+S1	O
+)	O
+.	O
+
+It	O
+is	O
+not	O
+clear	O
+what	O
+the	O
+basis	O
+of	O
+the	O
+contribution	O
+of	O
+2C	O
+to	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+could	O
+be	O
+.	O
+
+2C	O
+is	O
+involved	O
+in	O
+RNA	O
+synthesis	O
+and	O
+contains	O
+a	O
+nucleotide	O
+-	O
+binding	O
+domain	O
+,	O
+although	O
+none	O
+of	O
+the	O
+substitutions	O
+found	O
+in	O
+
+and	O
+
+lie	O
+within	O
+such	O
+a	O
+domain	O
+.	O
+
+An	O
+unlikely	O
+triple	O
+reversion	O
+would	O
+be	O
+required	O
+to	O
+eliminate	O
+the	O
+virulence	O
+-	O
+enhancing	O
+effect	O
+of	O
+the	O
+three	O
+mutations	O
+in	O
+2C	O
+.	O
+
+We	O
+propose	O
+that	O
+a	O
+higher	O
+robustness	O
+of	O
+the	O
+FMDV	B
+genome	O
+with	O
+regard	O
+to	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+rather	O
+than	O
+to	O
+replicative	O
+fitness	O
+in	O
+the	O
+same	O
+cells	O
+,	O
+underlies	O
+the	O
+different	O
+trajectories	O
+followed	O
+by	O
+fitness	O
+and	O
+virulence	O
+upon	O
+subjecting	O
+the	O
+virus	O
+to	O
+repeated	O
+bottleneck	O
+transfers	O
+.	O
+
+Obviously	O
+,	O
+we	O
+cannot	O
+exclude	O
+that	O
+parameters	O
+of	O
+the	O
+virus	O
+life	O
+cycle	O
+,	O
+other	O
+than	O
+fitness	O
+as	O
+measured	O
+in	O
+our	O
+experiments	O
+,	O
+could	O
+correlate	O
+with	O
+virulence	O
+for	O
+BHK	O
+-	O
+21	O
+.	O
+
+The	O
+comparative	O
+analysis	O
+of	O
+FMDV	B
+clones	O
+and	O
+populations	O
+shows	O
+that	O
+shifts	O
+in	O
+virulence	O
+can	O
+occur	O
+even	O
+through	O
+the	O
+evolution	O
+of	O
+a	O
+single	O
+viral	O
+clone	O
+(	O
+C	O
+-	O
+S8c1	O
+)	O
+,	O
+with	O
+its	O
+restricted	O
+genetic	O
+diversity	O
+prompted	O
+by	O
+different	O
+replication	O
+regimes	O
+in	O
+the	O
+same	O
+host	O
+cells	O
+,	O
+which	O
+also	O
+have	O
+a	O
+clonal	O
+origin	O
+(	O
+see	O
+Materials	O
+and	O
+Methods	O
+)	O
+.	O
+
+We	O
+conjecture	O
+that	O
+the	O
+demonstration	O
+that	O
+fitness	O
+and	O
+virulence	O
+can	O
+follow	O
+different	O
+evolutionary	O
+courses	O
+has	O
+been	O
+possible	O
+thanks	O
+to	O
+the	O
+consequences	O
+of	O
+the	O
+extreme	O
+passage	O
+regimes	O
+to	O
+which	O
+the	O
+viral	O
+populations	O
+were	O
+subjected	O
+:	O
+competitive	O
+evolution	O
+of	O
+an	O
+ample	O
+mutant	O
+spectra	O
+during	O
+repeated	O
+large	O
+population	O
+passages	O
+,	O
+and	O
+accumulation	O
+of	O
+deleterious	O
+(	O
+with	O
+regard	O
+to	O
+fitness	O
+,	O
+but	O
+not	O
+with	O
+regard	O
+to	O
+virulence	O
+)	O
+mutations	O
+upon	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+(	O
+predominance	O
+of	O
+genetic	O
+drift	O
+and	O
+operation	O
+of	O
+Muller	O
+'	O
+s	O
+ratchet	O
+)	O
+[	O
+12	O
+,	O
+15	O
+]	O
+.	O
+
+Implications	O
+for	O
+Models	O
+of	O
+Virulence	O
+
+It	O
+must	O
+be	O
+emphasized	O
+that	O
+fitness	O
+and	O
+virulence	O
+are	O
+relative	O
+values	O
+that	O
+pertain	O
+to	O
+a	O
+defined	O
+physical	O
+and	O
+biological	O
+environment	O
+.	O
+
+Virulence	O
+determinants	O
+of	O
+FMDV	B
+,	O
+identified	O
+here	O
+for	O
+BHK	O
+-	O
+21	O
+cells	O
+,	O
+need	O
+not	O
+apply	O
+to	O
+virulence	O
+for	O
+the	O
+natural	O
+animal	O
+hosts	O
+of	O
+FMDV	B
+[	O
+44	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+observation	O
+of	O
+a	O
+lack	O
+of	O
+correlation	O
+between	O
+fitness	O
+and	O
+virulence	O
+in	O
+a	O
+FMDV	B
+clone	O
+is	O
+relevant	O
+to	O
+current	O
+models	O
+of	O
+attenuation	O
+and	O
+virulence	O
+,	O
+since	O
+it	O
+shows	O
+that	O
+more	O
+virulent	O
+forms	O
+of	O
+a	O
+virus	O
+need	O
+not	O
+have	O
+a	O
+reproductive	O
+advantage	O
+,	O
+and	O
+that	O
+viral	O
+virulence	O
+is	O
+not	O
+necessarily	O
+a	O
+byproduct	O
+of	O
+viral	O
+fitness	O
+.	O
+
+Even	O
+if	O
+virulence	O
+is	O
+regarded	O
+as	O
+an	O
+unavoidable	O
+consequence	O
+of	O
+parasite	O
+adaptation	O
+[	O
+45	O
+]	O
+,	O
+virus	O
+de	O
+-	O
+adaptation	O
+(	O
+fitness	O
+loss	O
+)	O
+need	O
+not	O
+entail	O
+a	O
+decrease	O
+of	O
+virulence	O
+.	O
+
+Most	O
+current	O
+definitions	O
+of	O
+virulence	O
+include	O
+both	O
+the	O
+ability	O
+of	O
+the	O
+pathogen	O
+to	O
+multiply	O
+and	O
+to	O
+cause	O
+harm	O
+to	O
+its	O
+host	O
+;	O
+some	O
+authors	O
+,	O
+however	O
+,	O
+assume	O
+a	O
+direct	O
+relationship	O
+between	O
+fitness	O
+and	O
+capacity	O
+to	O
+produce	O
+disease	O
+[	O
+46	O
+-	O
+48	O
+]	O
+.	O
+
+In	O
+relating	O
+the	O
+results	O
+with	O
+FMDV	B
+to	O
+general	O
+models	O
+of	O
+virulence	O
+in	O
+host	O
+-	O
+parasite	O
+systems	O
+,	O
+it	O
+must	O
+be	O
+considered	O
+that	O
+in	O
+the	O
+FMDV	B
+system	O
+,	O
+evolution	O
+of	O
+the	O
+host	O
+BHK	O
+-	O
+21	O
+cells	O
+could	O
+not	O
+influence	O
+FMDV	B
+evolution	O
+,	O
+because	O
+clonal	O
+cell	O
+populations	O
+with	O
+a	O
+controlled	O
+passage	O
+history	O
+were	O
+supplied	O
+in	O
+constant	O
+numbers	O
+at	O
+each	O
+infection	O
+event	O
+(	O
+see	O
+Materials	O
+and	O
+Methods	O
+)	O
+.	O
+
+Therefore	O
+,	O
+changes	O
+in	O
+host	O
+density	O
+,	O
+or	O
+mobility	O
+,	O
+as	O
+well	O
+as	O
+pathogen	O
+survival	O
+in	O
+the	O
+external	O
+environment	O
+,	O
+all	O
+of	O
+which	O
+are	O
+relevant	O
+parameters	O
+in	O
+virulence	O
+models	O
+[	O
+48	O
+,	O
+49	O
+]	O
+,	O
+cannot	O
+play	O
+a	O
+role	O
+in	O
+our	O
+system	O
+.	O
+
+A	O
+consistent	O
+finding	O
+in	O
+serial	O
+passage	O
+experiments	O
+is	O
+that	O
+virulence	O
+of	O
+a	O
+parasite	O
+increases	O
+with	O
+passage	O
+number	O
+in	O
+a	O
+new	O
+host	O
+[	O
+50	O
+]	O
+.	O
+
+The	O
+results	O
+with	O
+FMDV	B
+infecting	O
+BHK	O
+-	O
+21	O
+cells	O
+cytolytically	O
+imply	O
+that	O
+the	O
+increase	O
+of	O
+virulence	O
+can	O
+be	O
+conditioned	O
+to	O
+the	O
+history	O
+of	O
+passage	O
+regimes	O
+undergone	O
+by	O
+a	O
+virus	O
+.	O
+
+The	O
+invariance	O
+of	O
+BHK	O
+-	O
+21	O
+cells	O
+in	O
+the	O
+course	O
+of	O
+serial	O
+cytolytic	O
+passages	O
+of	O
+FMDV	B
+is	O
+in	O
+contrast	O
+with	O
+the	O
+parallel	O
+system	O
+consisting	O
+of	O
+BHK	O
+-	O
+21	O
+cells	O
+persistently	O
+infected	O
+with	O
+FMDV	B
+C	O
+-	O
+S8c1	O
+[	O
+25	O
+]	O
+,	O
+in	O
+which	O
+the	O
+cells	O
+are	O
+passaged	O
+and	O
+coevolve	O
+with	O
+the	O
+resident	O
+virus	O
+[	O
+51	O
+]	O
+.	O
+
+Host	O
+-	O
+virus	O
+coevolution	O
+has	O
+generally	O
+favored	O
+a	O
+decrease	O
+of	O
+viral	O
+virulence	O
+in	O
+the	O
+field	O
+,	O
+a	O
+classical	O
+example	O
+being	O
+myxoma	B
+virus	I
+and	O
+myxomatosis	O
+in	O
+rabbits	B
+[	O
+52	O
+]	O
+.	O
+
+Our	O
+comparison	O
+of	O
+FMDV	B
+clones	O
+did	O
+not	O
+provide	O
+evidence	O
+of	O
+clones	O
+with	O
+high	O
+fitness	O
+and	O
+low	O
+virulence	O
+,	O
+which	O
+,	O
+with	O
+regard	O
+to	O
+natural	O
+hosts	O
+,	O
+is	O
+an	O
+aim	O
+of	O
+biomedicine	O
+to	O
+obtain	O
+vaccine	O
+strains	O
+.	O
+
+Yet	O
+,	O
+the	O
+existence	O
+of	O
+specific	O
+mutations	O
+that	O
+differentially	O
+affect	O
+fitness	O
+and	O
+virulence	O
+opens	O
+the	O
+way	O
+to	O
+engineer	O
+candidate	O
+vaccine	O
+strains	O
+unable	O
+to	O
+kill	O
+the	O
+host	O
+,	O
+while	O
+maintaining	O
+replicative	O
+competence	O
+.	O
+
+Virulence	O
+is	O
+,	O
+however	O
+,	O
+a	O
+feature	O
+of	O
+the	O
+host	O
+-	O
+parasite	O
+relationship	O
+[	O
+46	O
+]	O
+,	O
+and	O
+the	O
+mutations	O
+needed	O
+to	O
+impair	O
+virulence	O
+are	O
+expected	O
+to	O
+be	O
+host	O
+-	O
+dependent	O
+[	O
+53	O
+,	O
+54	O
+]	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Cells	O
+,	O
+viruses	O
+,	O
+and	O
+infections	O
+.	O
+
+The	O
+BHK	O
+-	O
+21	O
+cells	O
+used	O
+in	O
+the	O
+present	O
+study	O
+were	O
+cloned	O
+by	O
+end	O
+-	O
+point	O
+dilution	O
+,	O
+followed	O
+by	O
+preparation	O
+of	O
+a	O
+cell	O
+stock	O
+from	O
+a	O
+single	O
+cell	O
+;	O
+they	O
+were	O
+passaged	O
+a	O
+maximum	O
+of	O
+30	O
+times	O
+before	O
+being	O
+used	O
+for	O
+FMDV	B
+infection	O
+[	O
+25	O
+,	O
+51	O
+]	O
+.	O
+
+Procedures	O
+for	O
+cell	O
+growth	O
+,	O
+infection	O
+of	O
+BHK	O
+-	O
+21	O
+cell	O
+monolayers	O
+with	O
+FMDV	B
+in	O
+liquid	O
+medium	O
+,	O
+and	O
+plaque	O
+assays	O
+in	O
+semi	O
+-	O
+solid	O
+agar	O
+medium	O
+were	O
+carried	O
+out	O
+as	O
+previously	O
+described	O
+[	O
+11	O
+,	O
+19	O
+,	O
+25	O
+,	O
+27	O
+]	O
+.	O
+
+Mock	O
+-	O
+infected	O
+cells	O
+were	O
+handled	O
+in	O
+parallel	O
+in	O
+all	O
+infectivity	O
+and	O
+plaque	O
+assays	O
+to	O
+monitor	O
+absence	O
+of	O
+viral	O
+contamination	O
+.	O
+
+The	O
+FMDVs	B
+used	O
+in	O
+the	O
+present	O
+study	O
+(	O
+Figure	O
+1	O
+)	O
+are	O
+(	O
+i	O
+)	O
+the	O
+reference	O
+clone	O
+C	O
+-	O
+S8c1	O
+,	O
+which	O
+has	O
+been	O
+assigned	O
+a	O
+relative	O
+fitness	O
+of	O
+1	O
+.	O
+0	O
+[	O
+11	O
+]	O
+.	O
+
+(	O
+ii	O
+)	O
+MARLS	O
+,	O
+a	O
+monoclonal	O
+antibody	O
+escape	O
+mutant	O
+isolated	O
+from	O
+population	O
+C	O
+-	O
+S8c1p213	O
+[	O
+55	O
+]	O
+;	O
+MARLS	O
+has	O
+a	O
+fitness	O
+of	O
+25	O
+relative	O
+to	O
+C	O
+-	O
+S8c1	O
+[	O
+24	O
+]	O
+.	O
+
+(	O
+iii	O
+)	O
+C	O
+-	O
+S8p260p3d	O
+,	O
+a	O
+standard	O
+FMDV	B
+virus	O
+rescued	O
+by	O
+low	O
+MOI	O
+passage	O
+of	O
+C	O
+-	O
+S8p260	O
+.	O
+
+The	O
+latter	O
+is	O
+a	O
+virus	O
+that	O
+evolved	O
+by	O
+passage	O
+of	O
+C	O
+-	O
+S8c1	O
+at	O
+a	O
+high	O
+MOI	O
+,	O
+which	O
+resulted	O
+in	O
+dominance	O
+of	O
+two	O
+defective	O
+FMDV	B
+genomes	O
+(	O
+both	O
+including	O
+internal	O
+deletions	O
+)	O
+that	O
+were	O
+infectious	O
+by	O
+complementation	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+standard	O
+virus	O
+[	O
+22	O
+,	O
+24	O
+,	O
+28	O
+]	O
+;	O
+C	O
+-	O
+S8p260p3d	O
+has	O
+a	O
+relative	O
+fitness	O
+of	O
+20	O
+[	O
+24	O
+]	O
+.	O
+
+(	O
+iv	O
+)	O
+REDpt60	O
+,	O
+obtained	O
+after	O
+60	O
+successive	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+of	O
+RED	O
+(	O
+a	O
+monoclonal	O
+antibody	O
+escape	O
+mutant	O
+isolated	O
+from	O
+population	O
+C	O
+-	O
+S8c1p100	O
+)	O
+[	O
+20	O
+]	O
+;	O
+REDpt60	O
+has	O
+a	O
+fitness	O
+of	O
+1	O
+.	O
+9	O
+relative	O
+to	O
+C	O
+-	O
+S8c1	O
+.	O
+
+(	O
+v	O
+)	O
+C	O
+-	O
+S8c1p113	O
+,	O
+a	O
+viral	O
+population	O
+obtained	O
+after	O
+113	O
+serial	O
+cytolytic	O
+passages	O
+of	O
+C	O
+-	O
+S8c1	O
+at	O
+a	O
+high	O
+MOI	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+(	O
+2	O
+x	O
+106	O
+BHK	O
+-	O
+21	O
+cells	O
+infected	O
+with	O
+the	O
+virus	O
+contained	O
+in	O
+200	O
+mu	O
+l	O
+of	O
+the	O
+supernatant	O
+from	O
+the	O
+previous	O
+infection	O
+)	O
+.	O
+
+(	O
+vi	O
+)	O
+Clone	O
+
+,	O
+a	O
+biological	O
+clone	O
+isolated	O
+from	O
+population	O
+C	O
+-	O
+S8c1p113	O
+[	O
+11	O
+]	O
+;	O
+its	O
+relative	O
+fitness	O
+is	O
+26	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+(	O
+vii	O
+)	O
+Clone	O
+
+,	O
+obtained	O
+after	O
+95	O
+successive	O
+plaque	O
+-	O
+to	O
+-	O
+plaque	O
+transfers	O
+of	O
+
+[	O
+11	O
+]	O
+;	O
+its	O
+relative	O
+fitness	O
+is	O
+0	O
+.	O
+11	O
+[	O
+23	O
+]	O
+.	O
+
+Cell	O
+killing	O
+assay	O
+.	O
+
+The	O
+capacity	O
+of	O
+FMDV	B
+to	O
+kill	O
+BHK	O
+-	O
+21	O
+cells	O
+was	O
+measured	O
+as	O
+previously	O
+described	O
+[	O
+18	O
+,	O
+22	O
+]	O
+.	O
+
+The	O
+assay	O
+consists	O
+in	O
+determining	O
+the	O
+minimum	O
+number	O
+of	O
+PFU	O
+required	O
+to	O
+kill	O
+104	O
+BHK	O
+-	O
+21	O
+cells	O
+after	O
+variable	O
+times	O
+of	O
+infection	O
+.	O
+
+The	O
+assay	O
+was	O
+performed	O
+in	O
+M96	O
+multiwell	O
+plates	O
+with	O
+monolayers	O
+of	O
+104	O
+BHK	O
+-	O
+21	O
+cells	O
+per	O
+well	O
+infected	O
+with	O
+serial	O
+dilutions	O
+of	O
+virus	O
+.	O
+
+At	O
+different	O
+times	O
+postinfection	O
+,	O
+cells	O
+were	O
+fixed	O
+with	O
+2	O
+%	O
+formaldehyde	O
+and	O
+stained	O
+with	O
+2	O
+%	O
+crystal	O
+violet	O
+in	O
+2	O
+%	O
+formaldehyde	O
+.	O
+
+Results	O
+are	O
+expressed	O
+as	O
+the	O
+logarithm	O
+of	O
+the	O
+number	O
+of	O
+PFUs	O
+needed	O
+for	O
+complete	O
+cell	O
+killing	O
+(	O
+as	O
+judged	O
+by	O
+cell	O
+staining	O
+with	O
+crystal	O
+violet	O
+,	O
+with	O
+series	O
+of	O
+control	O
+wells	O
+with	O
+known	O
+numbers	O
+of	O
+cells	O
+)	O
+as	O
+a	O
+function	O
+of	O
+time	O
+postinfection	O
+[	O
+18	O
+,	O
+22	O
+]	O
+.	O
+
+Determination	O
+of	O
+relative	O
+fitness	O
+of	O
+
+.	O
+
+The	O
+relative	O
+fitness	O
+of	O
+FMDV	B
+
+was	O
+determined	O
+by	O
+growth	O
+competition	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+as	O
+previously	O
+described	O
+[	O
+7	O
+,	O
+10	O
+,	O
+11	O
+,	O
+24	O
+,	O
+56	O
+]	O
+.	O
+
+FMDV	B
+
+was	O
+mixed	O
+with	O
+appropriate	O
+proportions	O
+of	O
+
+,	O
+which	O
+was	O
+used	O
+as	O
+reference	O
+virus	O
+.	O
+
+This	O
+virus	O
+has	O
+a	O
+fitness	O
+8	O
+.	O
+5	O
+-	O
+fold	O
+higher	O
+than	O
+that	O
+of	O
+the	O
+reference	O
+clone	O
+of	O
+C	O
+-	O
+S8c1	O
+in	O
+BHK	O
+-	O
+21	O
+cells	O
+[	O
+7	O
+,	O
+10	O
+,	O
+11	O
+,	O
+24	O
+,	O
+56	O
+]	O
+.	O
+
+Four	O
+serial	O
+infections	O
+were	O
+carried	O
+out	O
+at	O
+MOI	O
+of	O
+0	O
+.	O
+1	O
+PFU	O
+/	O
+cell	O
+.	O
+
+The	O
+proportion	O
+of	O
+the	O
+two	O
+competing	O
+genomes	O
+at	O
+different	O
+passages	O
+was	O
+determined	O
+by	O
+real	O
+-	O
+time	O
+reverse	O
+transcription	O
+(	O
+RT	O
+)	O
+-	O
+PCR	O
+,	O
+employing	O
+primers	O
+5531wtnew	O
+and	O
+
+,	O
+which	O
+are	O
+able	O
+to	O
+discriminate	O
+FMDV	B
+
+RNA	O
+from	O
+
+RNA	O
+.	O
+
+The	O
+nucleotide	O
+sequences	O
+of	O
+the	O
+primers	O
+will	O
+be	O
+provided	O
+upon	O
+request	O
+.	O
+
+The	O
+fitness	O
+vector	O
+obtained	O
+for	O
+
+corresponded	O
+to	O
+the	O
+equation	O
+y	O
+=	O
+0	O
+,	O
+0206e1	O
+,	O
+1074x	O
+;	O
+R2	O
+=	O
+0	O
+.	O
+9507	O
+.	O
+
+The	O
+antilogarithm	O
+(	O
+base	O
+e	O
+)	O
+of	O
+the	O
+vector	O
+slope	O
+is	O
+the	O
+fitness	O
+of	O
+the	O
+assayed	O
+virus	O
+relative	O
+to	O
+the	O
+reference	O
+virus	O
+[	O
+56	O
+]	O
+.	O
+
+cDNA	O
+synthesis	O
+,	O
+molecular	O
+cloning	O
+,	O
+and	O
+nucleotide	O
+sequencing	O
+.	O
+
+Viral	O
+RNA	O
+was	O
+extracted	O
+by	O
+treatment	O
+with	O
+Trizol	O
+as	O
+previously	O
+described	O
+[	O
+57	O
+]	O
+.	O
+
+Reverse	O
+transcription	O
+of	O
+FMDV	B
+RNA	O
+was	O
+carried	O
+out	O
+with	O
+avian	B
+myeloblastosis	I
+virus	I
+reverse	O
+transcriptase	O
+(	O
+Promega	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+promega	O
+.	O
+com	O
+)	O
+or	O
+Transcriptor	O
+reverse	O
+transcriptase	O
+(	O
+Roche	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+roche	O
+.	O
+com	O
+)	O
+,	O
+and	O
+PCR	O
+amplification	O
+was	O
+performed	O
+by	O
+using	O
+either	O
+Ampli	O
+-	O
+Taq	O
+polymerase	O
+(	O
+PerkinElmer	O
+,	O
+http	O
+:	O
+/	O
+/	O
+las	O
+.	O
+perkinelmer	O
+.	O
+com	O
+)	O
+or	O
+an	O
+Expand	O
+High	O
+Fidelity	O
+polymerase	O
+system	O
+(	O
+Roche	O
+)	O
+,	O
+as	O
+instructed	O
+by	O
+the	O
+manufacturers	O
+.	O
+
+The	O
+FMDV	B
+genome	O
+-	O
+specific	O
+oligonucleotide	O
+primers	O
+used	O
+have	O
+been	O
+previously	O
+described	O
+[	O
+22	O
+,	O
+58	O
+]	O
+.	O
+
+In	O
+all	O
+RT	O
+-	O
+PCR	O
+amplifications	O
+,	O
+negative	O
+amplification	O
+controls	O
+,	O
+including	O
+all	O
+reaction	O
+components	O
+except	O
+template	O
+RNA	O
+,	O
+were	O
+run	O
+in	O
+parallel	O
+to	O
+monitor	O
+absence	O
+of	O
+contamination	O
+.	O
+
+Chimeric	O
+viruses	O
+containing	O
+selected	O
+regions	O
+of	O
+
+in	O
+the	O
+genetic	O
+background	O
+of	O
+C	O
+-	O
+S8c1	O
+(	O
+Figure	O
+4	O
+)	O
+were	O
+obtained	O
+by	O
+replacing	O
+the	O
+corresponding	O
+DNA	O
+fragment	O
+of	O
+pMT28	O
+by	O
+a	O
+cDNA	O
+copy	O
+of	O
+
+RNA	O
+,	O
+using	O
+specific	O
+restriction	O
+sites	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+436	O
+-	O
+2046	O
+)	O
+,	O
+a	O
+chimera	O
+that	O
+included	O
+nucleotides	O
+436	O
+to	O
+2046	O
+of	O
+
+(	O
+the	O
+residue	O
+numbering	O
+of	O
+the	O
+FMDV	B
+genome	O
+is	O
+as	O
+in	O
+[	O
+11	O
+]	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+NR2	O
+and	O
+JH2	O
+,	O
+and	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Hpa	O
+I	O
+(	O
+position	O
+436	O
+)	O
+and	O
+Xba	O
+I	O
+(	O
+2046	O
+)	O
+,	O
+and	O
+ligated	O
+into	O
+pMT28	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+2046	O
+-	O
+3760	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+2R1New	O
+and	O
+pU	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Xba	O
+I	O
+(	O
+2046	O
+)	O
+and	O
+Avr	O
+II	O
+(	O
+3760	O
+)	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+3760	O
+-	O
+5839	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+3R2New	O
+and	O
+3CD1	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Avr	O
+II	O
+(	O
+3760	O
+)	O
+and	O
+Rsr	O
+II	O
+(	O
+5839	O
+)	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+5839	O
+-	O
+7427	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+5531	O
+wt	O
+new	O
+and	O
+C	O
+-	O
+Not	O
+-	O
+Pol	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Rsr	O
+II	O
+(	O
+5839	O
+)	O
+and	O
+Bam	O
+HI	O
+(	O
+7427	O
+)	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+436	O
+-	O
+3760	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+NR2	O
+and	O
+JH2	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Hpa	O
+I	O
+(	O
+position	O
+436	O
+)	O
+and	O
+Xba	O
+I	O
+(	O
+2046	O
+)	O
+,	O
+and	O
+ligated	O
+into	O
+pMT28	O
+/	O
+
+(	O
+2046	O
+-	O
+3760	O
+)	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+3760	O
+-	O
+7427	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+3R2New	O
+and	O
+3CD1	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Avr	O
+II	O
+(	O
+3760	O
+)	O
+and	O
+Rsr	O
+II	O
+(	O
+5839	O
+)	O
+,	O
+and	O
+ligated	O
+into	O
+pMT28	O
+/	O
+
+(	O
+5839	O
+-	O
+7427	O
+)	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+2046	O
+-	O
+7427	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+2R1New	O
+and	O
+pU	O
+,	O
+and	O
+then	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Xba	O
+I	O
+(	O
+2046	O
+)	O
+and	O
+Avr	O
+II	O
+(	O
+3760	O
+)	O
+,	O
+and	O
+ligated	O
+into	O
+pMT28	O
+/	O
+
+(	O
+3760	O
+-	O
+7427	O
+)	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+/	O
+
+(	O
+436	O
+-	O
+7427	O
+)	O
+,	O
+
+RNA	O
+was	O
+amplified	O
+by	O
+RT	O
+-	O
+PCR	O
+using	O
+primers	O
+NR2	O
+and	O
+JH2	O
+;	O
+the	O
+cDNA	O
+was	O
+digested	O
+with	O
+Hpa	O
+I	O
+(	O
+position	O
+436	O
+)	O
+and	O
+Xba	O
+I	O
+(	O
+2046	O
+)	O
+,	O
+and	O
+ligated	O
+into	O
+pMT28	O
+/	O
+
+(	O
+2046	O
+-	O
+7427	O
+)	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+To	O
+obtain	O
+
+/	O
+2C	O
+-	O
+3A	O
+(	O
+pMT28	O
+)	O
+,	O
+pMT28	O
+was	O
+digested	O
+with	O
+Bgl	O
+II	O
+(	O
+4201	O
+)	O
+and	O
+Rsr	O
+II	O
+(	O
+5839	O
+)	O
+,	O
+and	O
+a	O
+DNA	O
+fragment	O
+including	O
+wild	O
+-	O
+type	O
+2C	O
+-	O
+3A	O
+-	O
+coding	O
+region	O
+was	O
+inserted	O
+into	O
+pMT28	O
+/	O
+
+(	O
+436	O
+-	O
+7427	O
+)	O
+DNA	O
+digested	O
+with	O
+the	O
+same	O
+enzymes	O
+.	O
+
+DNA	O
+ligation	O
+,	O
+transformation	O
+of	O
+Escherichia	B
+coli	I
+DH5	O
+alpha	O
+,	O
+isolation	O
+of	O
+DNA	O
+from	O
+bacterial	O
+colonies	O
+,	O
+and	O
+characterization	O
+of	O
+DNA	O
+by	O
+restriction	O
+enzyme	O
+digestion	O
+were	O
+performed	O
+by	O
+standard	O
+procedures	O
+[	O
+59	O
+]	O
+.	O
+
+The	O
+primers	O
+used	O
+for	O
+molecular	O
+cloning	O
+and	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+are	O
+described	O
+in	O
+Table	O
+S3	O
+.	O
+
+To	O
+obtain	O
+FMDV	B
+C	O
+-	O
+S8c1	O
+containing	O
+the	O
+mutations	O
+found	O
+in	O
+gene	O
+2C	O
+of	O
+
+,	O
+plasmid	O
+pMT28	O
+was	O
+subjected	O
+to	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+using	O
+an	O
+oligonucleotide	O
+including	O
+the	O
+required	O
+nucleotide	O
+replacement	O
+,	O
+and	O
+3R2New	O
+or	O
+3CD1	O
+as	O
+external	O
+oligonucleotide	O
+primer	O
+(	O
+Table	O
+S3	O
+;	O
+Figure	O
+4	O
+)	O
+.	O
+
+A	O
+DNA	O
+fragment	O
+termed	O
+A	O
+was	O
+obtained	O
+by	O
+subjecting	O
+plasmid	O
+pMT28	O
+to	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+using	O
+primers	O
+(	O
+reverse	O
+)	O
+mutSNu	O
+,	O
+mutTAu	O
+,	O
+and	O
+mutQHu	O
+(	O
+to	O
+introduce	O
+mutations	O
+S80N	O
+,	O
+T256A	O
+,	O
+and	O
+Q263H	O
+,	O
+respectively	O
+)	O
+and	O
+an	O
+external	O
+oligonucleotide	O
+primer	O
+(	O
+3R2New	O
+,	O
+forward	O
+)	O
+.	O
+
+A	O
+DNA	O
+fragment	O
+termed	O
+B	O
+was	O
+obtained	O
+amplifying	O
+pMT28	O
+with	O
+primers	O
+(	O
+forward	O
+)	O
+mutSNd	O
+,	O
+mutTAd	O
+,	O
+and	O
+mutQHd	O
+(	O
+to	O
+introduce	O
+mutations	O
+S80N	O
+,	O
+T256A	O
+,	O
+and	O
+Q263H	O
+,	O
+respectively	O
+)	O
+and	O
+an	O
+external	O
+oligonucleotide	O
+primer	O
+(	O
+3CD1	O
+,	O
+reverse	O
+)	O
+.	O
+
+DNA	O
+fragments	O
+A	O
+and	O
+B	O
+,	O
+including	O
+the	O
+desired	O
+mutations	O
+,	O
+were	O
+recombined	O
+by	O
+shuffling	O
+PCR	O
+using	O
+equimolar	O
+amounts	O
+of	O
+DNA	O
+fragments	O
+and	O
+two	O
+external	O
+primers	O
+(	O
+3R2New	O
+and	O
+3CD1	O
+)	O
+.	O
+
+The	O
+DNA	O
+with	O
+the	O
+desired	O
+mutation	O
+(	O
+s	O
+)	O
+in	O
+the	O
+2C	O
+gene	O
+was	O
+digested	O
+with	O
+Avr	O
+II	O
+(	O
+genomic	O
+position	O
+3760	O
+)	O
+and	O
+Rsr	O
+II	O
+(	O
+position	O
+5839	O
+)	O
+,	O
+and	O
+cloned	O
+into	O
+pMT28	O
+to	O
+generate	O
+pMT28	O
+(	O
+SN	O
+)	O
+,	O
+pMT28	O
+(	O
+TA	O
+)	O
+,	O
+and	O
+pMT28	O
+(	O
+QH	O
+)	O
+.	O
+
+To	O
+obtain	O
+pMT28	O
+(	O
+SN	O
+,	O
+TA	O
+,	O
+QH	O
+)	O
+,	O
+plasmid	O
+pMT28	O
+(	O
+SN	O
+)	O
+was	O
+subjected	O
+to	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+to	O
+introduce	O
+mutation	O
+T256A	O
+in	O
+a	O
+similar	O
+way	O
+as	O
+described	O
+above	O
+,	O
+and	O
+then	O
+,	O
+plasmid	O
+pMT28	O
+(	O
+SN	O
+,	O
+TA	O
+)	O
+was	O
+subjected	O
+to	O
+site	O
+-	O
+directed	O
+mutagenesis	O
+to	O
+introduce	O
+mutation	O
+Q263H	O
+.	O
+
+All	O
+chimeric	O
+viruses	O
+and	O
+mutants	O
+were	O
+analyzed	O
+by	O
+nucleotide	O
+sequencing	O
+using	O
+Big	O
+Dye	O
+Terminator	O
+Cycle	O
+Sequencing	O
+kit	O
+(	O
+Abi	O
+Prism	O
+;	O
+PerkinElmer	O
+)	O
+and	O
+sequencer	O
+ABI373	O
+as	O
+previously	O
+described	O
+[	O
+58	O
+]	O
+.	O
+
+Sequences	O
+were	O
+analyzed	O
+using	O
+DNASTAR	O
+4	O
+.	O
+0	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+dnastar	O
+.	O
+com	O
+)	O
+,	O
+GeneDoc	O
+,	O
+and	O
+GCC	O
+(	O
+University	O
+of	O
+Wisconsin	O
+)	O
+.	O
+
+Each	O
+sequence	O
+was	O
+determined	O
+at	O
+least	O
+twice	O
+,	O
+with	O
+products	O
+obtained	O
+using	O
+different	O
+oligonucleotide	O
+primers	O
+.	O
+
+DNA	O
+from	O
+pMT28	O
+or	O
+its	O
+recombinant	O
+and	O
+mutant	O
+derivatives	O
+was	O
+linearized	O
+with	O
+Nde	O
+I	O
+and	O
+transcribed	O
+with	O
+SP6	O
+RNA	O
+polymerase	O
+as	O
+previously	O
+described	O
+[	O
+22	O
+,	O
+27	O
+]	O
+.	O
+
+Transcript	O
+RNA	O
+integrity	O
+and	O
+concentration	O
+were	O
+estimated	O
+by	O
+agarose	O
+gel	O
+electrophoresis	O
+,	O
+in	O
+parallel	O
+runs	O
+with	O
+known	O
+amounts	O
+of	O
+standard	O
+C	O
+-	O
+S8c1	O
+RNA	O
+.	O
+
+BHK	O
+-	O
+21	O
+cell	O
+monolayers	O
+(	O
+70	O
+%	O
+confluent	O
+,	O
+about	O
+1	O
+x	O
+106	O
+cells	O
+)	O
+were	O
+transfected	O
+with	O
+RNA	O
+transcripts	O
+(	O
+1	O
+mu	O
+g	O
+RNA	O
+)	O
+using	O
+lipofectin	O
+as	O
+previously	O
+described	O
+[	O
+59	O
+]	O
+.	O
+
+Virus	O
+was	O
+collected	O
+from	O
+the	O
+culture	O
+supernatant	O
+at	O
+72	O
+h	O
+post	O
+-	O
+transfection	O
+.	O
+
+The	O
+virus	O
+obtained	O
+by	O
+transfection	O
+was	O
+passaged	O
+twice	O
+before	O
+using	O
+it	O
+in	O
+biological	O
+studies	O
+.	O
+
+RNA	O
+was	O
+extracted	O
+and	O
+sequenced	O
+to	O
+ascertain	O
+that	O
+the	O
+virus	O
+maintained	O
+the	O
+genomic	O
+structure	O
+and	O
+mutations	O
+of	O
+the	O
+initial	O
+transcript	O
+.	O
+
+Consensus	O
+genomic	O
+nucleotide	O
+sequences	O
+of	O
+FMDV	B
+clones	O
+were	O
+obtained	O
+by	O
+RT	O
+-	O
+PCR	O
+amplification	O
+of	O
+virion	O
+RNA	O
+using	O
+specific	O
+primers	O
+[	O
+7	O
+,	O
+22	O
+,	O
+28	O
+]	O
+.	O
+
+Supporting	O
+Information	O
+
+Accession	O
+Numbers	O
+
+The	O
+GenBank	O
+accession	O
+numbers	O
+for	O
+the	O
+C	O
+-	O
+S8c1	O
+,	O
+
+,	O
+
+,	O
+CS8p260p3d	O
+,	O
+and	O
+MARLS	O
+genomic	O
+sequences	O
+are	O
+AJ133357	O
+,	O
+AM409190	O
+,	O
+AM409325	O
+,	O
+DQ409185	O
+,	O
+and	O
+AF274010	O
+,	O
+respectively	O
+.	O
+
+Nucleotide	O
+and	O
+amino	O
+acid	O
+sequences	O
+for	O
+picornaviruses	O
+can	O
+be	O
+found	O
+at	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+iah	O
+.	O
+bbsrc	O
+.	O
+ac	O
+.	O
+uk	O
+/	O
+virus	O
+/	O
+picornaviridae	O
+/	O
+SequenceDatabase	O
+/	O
+3Ddatabase	O
+/	O
+3D	O
+.	O
+HTM	O
+.	O
+
+Human	B
+growth	O
+hormone	O
+(	O
+GH1	O
+)	O
+gene	O
+polymorphism	O
+map	O
+in	O
+a	O
+normal	O
+-	O
+statured	O
+adult	O
+population	O
+
+Abstract	O
+
+Objective	O
+
+GH1	O
+gene	O
+presents	O
+a	O
+complex	O
+map	O
+of	O
+single	O
+nucleotide	O
+polymorphisms	O
+(	O
+SNPs	O
+)	O
+in	O
+the	O
+entire	O
+promoter	O
+,	O
+coding	O
+and	O
+noncoding	O
+regions	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+study	O
+was	O
+to	O
+establish	O
+the	O
+complete	O
+map	O
+of	O
+GH1	O
+gene	O
+SNPs	O
+in	O
+our	O
+control	O
+normal	O
+population	O
+and	O
+to	O
+analyse	O
+its	O
+association	O
+with	O
+adult	O
+height	O
+.	O
+
+Design	O
+,	O
+subjects	O
+and	O
+measurements	O
+
+A	O
+systematic	O
+GH1	O
+gene	O
+analysis	O
+was	O
+designed	O
+in	O
+a	O
+control	O
+population	O
+of	O
+307	O
+adults	O
+of	O
+both	O
+sexes	O
+with	O
+height	O
+normally	O
+distributed	O
+within	O
+normal	O
+range	O
+for	O
+the	O
+same	O
+population	O
+:	O
+-	O
+2	O
+standard	O
+deviation	O
+scores	O
+(	O
+SDS	O
+)	O
+to	O
++	O
+2	O
+SDS	O
+.	O
+
+An	O
+analysis	O
+was	O
+performed	O
+on	O
+individual	O
+and	O
+combined	O
+genotype	O
+associations	O
+with	O
+adult	O
+height	O
+.	O
+
+Results	O
+
+Twenty	O
+-	O
+five	O
+SNPs	O
+presented	O
+a	O
+frequency	O
+over	O
+1	O
+%	O
+:	O
+11	O
+in	O
+the	O
+promoter	O
+(	O
+P1	O
+to	O
+P11	O
+)	O
+,	O
+three	O
+in	O
+the	O
+5	O
+'	O
+UTR	O
+region	O
+(	O
+P12	O
+to	O
+P14	O
+)	O
+,	O
+one	O
+in	O
+exon	O
+1	O
+(	O
+P15	O
+)	O
+,	O
+three	O
+in	O
+intron	O
+1	O
+(	O
+P16	O
+to	O
+P18	O
+)	O
+,	O
+two	O
+in	O
+intron	O
+2	O
+(	O
+P19	O
+and	O
+P20	O
+)	O
+,	O
+two	O
+in	O
+exon	O
+4	O
+(	O
+P21	O
+and	O
+P22	O
+)	O
+and	O
+three	O
+in	O
+intron	O
+4	O
+(	O
+P23	O
+to	O
+P25	O
+)	O
+.	O
+
+Twenty	O
+-	O
+nine	O
+additional	O
+changes	O
+with	O
+frequencies	O
+under	O
+1	O
+%	O
+were	O
+found	O
+in	O
+29	O
+subjects	O
+.	O
+
+P8	O
+,	O
+P19	O
+,	O
+P20	O
+and	O
+P25	O
+had	O
+not	O
+been	O
+previously	O
+described	O
+.	O
+
+P6	O
+,	O
+P12	O
+,	O
+P17	O
+and	O
+P25	O
+accounted	O
+for	O
+6	O
+.	O
+2	O
+%	O
+of	O
+the	O
+variation	O
+in	O
+adult	O
+height	O
+(	O
+P	O
+=	O
+0	O
+.	O
+0007	O
+)	O
+in	O
+this	O
+population	O
+with	O
+genotypes	O
+A	O
+/	O
+G	O
+at	O
+P6	O
+,	O
+G	O
+/	O
+G	O
+at	O
+P6	O
+and	O
+A	O
+/	O
+G	O
+at	O
+P12	O
+decreasing	O
+height	O
+SDS	O
+(	O
+-	O
+0	O
+.	O
+063	O
++	O
+/	O
+-	O
+0	O
+.	O
+031	O
+,	O
+-	O
+0	O
+.	O
+693	O
++	O
+/	O
+-	O
+0	O
+.	O
+350	O
+and	O
+-	O
+0	O
+.	O
+489	O
++	O
+/	O
+-	O
+0	O
+.	O
+265	O
+,	O
+Mean	O
++	O
+/	O
+-	O
+SE	O
+)	O
+and	O
+genotypes	O
+A	O
+/	O
+T	O
+at	O
+P17	O
+and	O
+T	O
+/	O
+G	O
+at	O
+P25	O
+increasing	O
+height	O
+SDS	O
+(	O
++	O
+1	O
+.	O
+094	O
++	O
+/	O
+-	O
+0	O
+.	O
+456	O
+and	O
++	O
+1	O
+.	O
+184	O
++	O
+/	O
+-	O
+0	O
+.	O
+432	O
+)	O
+.	O
+
+Conclusions	O
+
+This	O
+study	O
+established	O
+the	O
+GH1	O
+gene	O
+sequence	O
+variation	O
+map	O
+in	O
+a	O
+normal	O
+adult	O
+height	O
+control	O
+population	O
+confirming	O
+the	O
+high	O
+density	O
+of	O
+SNPs	O
+in	O
+a	O
+relatively	O
+small	O
+gene	O
+.	O
+
+Our	O
+study	O
+shows	O
+that	O
+the	O
+more	O
+frequent	O
+SNPs	O
+did	O
+not	O
+significantly	O
+contribute	O
+to	O
+height	O
+determination	O
+,	O
+while	O
+only	O
+one	O
+promoter	O
+and	O
+two	O
+intronic	O
+SNPs	O
+contributed	O
+significantly	O
+to	O
+it	O
+.	O
+
+Studies	O
+in	O
+larger	O
+populations	O
+will	O
+have	O
+to	O
+confirm	O
+the	O
+associations	O
+and	O
+in	O
+vitro	O
+functional	O
+studies	O
+will	O
+elucidate	O
+the	O
+mechanisms	O
+involved	O
+.	O
+
+Systematic	O
+GH1	O
+gene	O
+analysis	O
+in	O
+patients	B
+with	O
+growth	O
+delay	O
+and	O
+suspected	O
+GH	O
+deficiency	O
+/	O
+insufficiency	O
+will	O
+clarify	O
+whether	O
+different	O
+SNP	O
+frequencies	O
+and	O
+/	O
+or	O
+the	O
+presence	O
+of	O
+different	O
+sequence	O
+changes	O
+may	O
+be	O
+associated	O
+with	O
+phenotypes	O
+in	O
+them	O
+.	O
+
+Introduction	O
+
+Human	B
+skeletal	O
+growth	O
+and	O
+final	O
+height	O
+attainment	O
+are	O
+a	O
+result	O
+of	O
+a	O
+multifactorial	O
+regulation	O
+involving	O
+systemic	O
+and	O
+local	O
+hormones	O
+,	O
+growth	O
+and	O
+nutritional	O
+factors	O
+,	O
+lifestyle	O
+and	O
+genetic	O
+factors	O
+.	O
+
+Heritability	O
+estimates1	O
+and	O
+genome	O
+-	O
+wide	O
+linkage	O
+analysis2	O
+have	O
+shown	O
+that	O
+genetic	O
+factors	O
+play	O
+a	O
+major	O
+role	O
+in	O
+determining	O
+stature	O
+.	O
+
+Among	O
+these	O
+factors	O
+,	O
+the	O
+GH	O
+-	O
+IGF	O
+-	O
+I	O
+axis	O
+plays	O
+an	O
+important	O
+role	O
+during	O
+postnatal	O
+life	O
+,	O
+and	O
+associations	O
+between	O
+structural	O
+variations	O
+in	O
+its	O
+genes	O
+and	O
+height	O
+are	O
+currently	O
+under	O
+study	O
+.	O
+3	O
+Although	O
+growth	O
+hormone	O
+(	O
+GH	O
+)	O
+deficiency	O
+is	O
+a	O
+well	O
+-	O
+known	O
+cause	O
+of	O
+growth	O
+retardation	O
+,	O
+which	O
+responds	O
+to	O
+GH	O
+replacement	O
+therapy	O
+,	O
+the	O
+diagnosis	O
+and	O
+physiopathological	O
+mechanisms	O
+for	O
+the	O
+so	O
+-	O
+called	O
+'	O
+idiopathic	O
+isolated	O
+GH	O
+deficiency	O
+'	O
+(	O
+IIGHD	O
+)	O
+require	O
+further	O
+clarification	O
+.	O
+
+In	O
+addition	O
+,	O
+GH	O
+secretion	O
+levels	O
+and	O
+markers	O
+of	O
+GH	O
+biological	O
+activity	O
+have	O
+been	O
+demonstrated	O
+to	O
+be	O
+specific	O
+and	O
+sensitive	O
+only	O
+in	O
+major	O
+deficiency	O
+states	O
+.	O
+4	O
+,	O
+5	O
+Genetic	O
+causes	O
+of	O
+GH	O
+deficiency	O
+within	O
+the	O
+GH1	O
+gene	O
+have	O
+been	O
+established	O
+;	O
+however	O
+,	O
+they	O
+are	O
+rarely	O
+recognized	O
+and	O
+only	O
+sought	O
+in	O
+major	O
+GH	O
+deficiency	O
+states	O
+during	O
+childhood	O
+and	O
+in	O
+family	O
+studies	O
+.	O
+3	O
+GH1	O
+gene	O
+,	O
+located	O
+at	O
+17q22	O
+-	O
+24	O
+,	O
+is	O
+a	O
+component	O
+of	O
+the	O
+GH	O
+gene	O
+cluster	O
+in	O
+which	O
+five	O
+genes	O
+evolving	O
+from	O
+a	O
+common	O
+ancestor	O
+are	O
+91	O
+-	O
+99	O
+%	O
+sequence	O
+conserved	O
+(	O
+paralogues	O
+)	O
+.	O
+6	O
+GH1	O
+is	O
+more	O
+abundantly	O
+expressed	O
+in	O
+pituitary	O
+cells	O
+,	O
+while	O
+the	O
+other	O
+four	O
+genes	O
+are	O
+expressed	O
+in	O
+placental	O
+tissue	O
+.	O
+
+Large	O
+deletions	O
+within	O
+the	O
+GH1	O
+gene	O
+cluster	O
+were	O
+described	O
+first	O
+followed	O
+by	O
+point	O
+mutations	O
+,	O
+the	O
+majority	O
+of	O
+which	O
+affect	O
+introns	O
+3	O
+or	O
+4	O
+,	O
+provoke	O
+skipping	O
+of	O
+exon	O
+3	O
+product	O
+and	O
+exert	O
+a	O
+dominant	O
+effect	O
+.	O
+3	O
+,	O
+7	O
+,	O
+8	O
+More	O
+recently	O
+,	O
+the	O
+presence	O
+of	O
+single	O
+nucleotide	O
+polymorphic	O
+points	O
+(	O
+SNPs	O
+)	O
+in	O
+the	O
+promoter	O
+region	O
+or	O
+in	O
+intron	O
+4	O
+of	O
+the	O
+GH1	O
+gene	O
+have	O
+been	O
+described9	O
+-	O
+12	O
+and	O
+associations	O
+with	O
+promoter	O
+allele	O
+activities	O
+or	O
+with	O
+GH	O
+secretion	O
+efficacy	O
+and	O
+circulating	O
+IGF	O
+-	O
+I	O
+levels	O
+in	O
+growth	O
+-	O
+retarded	O
+patients	B
+have	O
+also	O
+been	O
+described	O
+.	O
+11	O
+,	O
+12	O
+Other	O
+studies	O
+have	O
+analysed	O
+several	O
+GH1	O
+gene	O
+SNP	O
+genotypes	O
+as	O
+related	O
+to	O
+the	O
+incidence	O
+of	O
+neoplasia	O
+,	O
+with	O
+a	O
+positive	O
+association	O
+with	O
+colorectal	O
+neoplasia	O
+for	O
+intron	O
+4	O
+SNP	O
+,	O
+13	O
+a	O
+negative	O
+result	O
+for	O
+breast	O
+carcinoma14	O
+,	O
+15	O
+or	O
+a	O
+positive	O
+one	O
+for	O
+breast	O
+cancer	O
+risk	O
+.	O
+16	O
+,	O
+17	O
+In	O
+addition	O
+,	O
+a	O
+recent	O
+study	O
+in	O
+a	O
+cohort	O
+of	O
+adults	O
+over	O
+ages	O
+60	O
+years	O
+detected	O
+a	O
+significant	O
+association	O
+between	O
+genotypes	O
+at	O
+one	O
+SNP	O
+in	O
+the	O
+GH1	O
+gene	O
+promoter	O
+region	O
+and	O
+at	O
+the	O
+intron	O
+4	O
+SNP	O
+described	O
+by	O
+Hasegawa	O
+et	O
+al	O
+.	O
+11	O
+with	O
+baseline	O
+bone	O
+density	O
+and	O
+accelerated	O
+bone	O
+loss	O
+together	O
+with	O
+an	O
+interaction	O
+with	O
+weight	O
+at	O
+1	O
+year	O
+.	O
+18	O
+Intron	O
+4	O
+SNP	O
+described	O
+by	O
+Hasegawa	O
+et	O
+al	O
+.	O
+11	O
+has	O
+also	O
+been	O
+associated	O
+,	O
+in	O
+women	B
+,	O
+with	O
+shorter	O
+body	O
+height	O
+and	O
+reduced	O
+mortality	O
+,	O
+19	O
+whereas	O
+another	O
+intron	O
+4	O
+SNP	O
+(	O
+T1169A	O
+)	O
+has	O
+been	O
+associated	O
+in	O
+both	O
+sexes	O
+with	O
+a	O
+favourable	O
+metabolic	O
+profile	O
+.	O
+20	O
+A	O
+systematic	O
+SNP	O
+study	O
+was	O
+conducted	O
+by	O
+Adkins	O
+et	O
+al	O
+.	O
+21	O
+in	O
+GH1	O
+promoter	O
+,	O
+coding	O
+and	O
+noncoding	O
+regions	O
+in	O
+DNAs	O
+from	O
+placental	O
+tissues	O
+,	O
+and	O
+analysis	O
+of	O
+associations	O
+between	O
+genotypes	O
+and	O
+birth	O
+weight	O
+revealed	O
+an	O
+association	O
+between	O
+an	O
+alternate	O
+nucleotide	O
+at	O
+-	O
+1	O
+and	O
++	O
+3	O
+of	O
+translation	O
+initiation	O
+site	O
+and	O
+fetal	O
+growth	O
+restriction	O
+.	O
+
+However	O
+,	O
+no	O
+systematic	O
+GH1	O
+gene	O
+analysis	O
+in	O
+the	O
+entire	O
+promoter	O
+,	O
+coding	O
+and	O
+noncoding	O
+regions	O
+has	O
+been	O
+conducted	O
+in	O
+adults	O
+to	O
+establish	O
+the	O
+map	O
+of	O
+structural	O
+variation	O
+and	O
+its	O
+possible	O
+association	O
+with	O
+height	O
+.	O
+
+The	O
+relatively	O
+short	O
+size	O
+of	O
+the	O
+entire	O
+gene	O
+permits	O
+a	O
+complete	O
+analysis	O
+which	O
+is	O
+,	O
+nevertheless	O
+,	O
+hampered	O
+by	O
+the	O
+need	O
+to	O
+avoid	O
+amplification	O
+of	O
+any	O
+other	O
+of	O
+the	O
+GH	O
+cluster	O
+genes	O
+(	O
+paralogues	O
+)	O
+and	O
+the	O
+high	O
+density	O
+of	O
+sequence	O
+variations	O
+.	O
+
+To	O
+obtain	O
+normative	O
+data	O
+for	O
+subsequent	O
+analysis	O
+of	O
+GH1	O
+gene	O
+contribution	O
+to	O
+IIGHD	O
+in	O
+children	B
+,	O
+a	O
+systematic	O
+GH1	O
+gene	O
+structural	O
+analysis	O
+was	O
+designed	O
+in	O
+a	O
+normal	O
+adult	O
+control	O
+population	O
+to	O
+establish	O
+the	O
+GH1	O
+gene	O
+SNP	O
+map	O
+in	O
+adults	O
+from	O
+our	O
+population	O
+with	O
+heights	O
+within	O
+the	O
+normal	O
+range	O
+,	O
+determine	O
+the	O
+genotype	O
+frequencies	O
+and	O
+analyse	O
+possible	O
+associations	O
+between	O
+individual	O
+and	O
+combined	O
+SNPs	O
+with	O
+height	O
+.	O
+
+Subjects	O
+and	O
+methods	O
+
+Subjects	O
+
+A	O
+total	O
+of	O
+307	O
+adult	O
+subjects	O
+of	O
+both	O
+sexes	O
+(	O
+164	O
+women	B
+and	O
+143	O
+men	B
+)	O
+were	O
+recruited	O
+from	O
+hospital	O
+personnel	O
+and	O
+parents	O
+of	O
+patients	B
+with	O
+no	O
+history	O
+of	O
+growth	O
+retardation	O
+.	O
+
+Subjects	O
+had	O
+to	O
+fulfil	O
+the	O
+following	O
+criteria	O
+:	O
+Iberian	O
+Peninsular	O
+(	O
+except	O
+Basque	O
+)	O
+family	O
+origin	O
+and	O
+no	O
+family	O
+history	O
+of	O
+pathological	O
+short	O
+stature	O
+.	O
+
+A	O
+single	O
+subject	O
+per	O
+family	O
+was	O
+included	O
+.	O
+
+The	O
+protocol	O
+was	O
+approved	O
+by	O
+the	O
+Hospital	O
+Vall	O
+d	O
+'	O
+Hebron	O
+Ethics	O
+Committee	O
+and	O
+written	O
+informed	O
+consent	O
+was	O
+obtained	O
+from	O
+each	O
+participant	B
+.	O
+
+Height	O
+standard	O
+deviation	O
+scores	O
+(	O
+height	O
+SDS	O
+)	O
+were	O
+calculated	O
+according	O
+to	O
+sex	O
+-	O
+specific	O
+reference	O
+growth	O
+charts	O
+for	O
+the	O
+Spanish	O
+population	O
+(	O
+Carrascosa	O
+et	O
+al	O
+.	O
+22	O
+charts	O
+were	O
+used	O
+for	O
+subjects	O
+under	O
+ages	O
+30	O
+years	O
+and	O
+Hern	O
+a	O
+ndez	O
+et	O
+al	O
+.	O
+23	O
+for	O
+subjects	O
+aged	O
+30	O
+-	O
+50	O
+years	O
+)	O
+.	O
+
+Only	O
+individuals	O
+with	O
+height	O
+SDS	O
+between	O
+-	O
+2	O
+and	O
++	O
+2	O
+SDS	O
+were	O
+included	O
+in	O
+the	O
+study	O
+(	O
+mean	O
+-	O
+0	O
+.	O
+016	O
+;	O
+32	O
+women	B
+and	O
+28	O
+men	B
+between	O
+-	O
+2	O
+.	O
+000	O
+and	O
+-	O
+1	O
+.	O
+010	O
+;	O
+99	O
+women	B
+and	O
+80	O
+men	B
+between	O
+-	O
+1	O
+.	O
+000	O
+and	O
++	O
+0	O
+.	O
+910	O
+;	O
+33	O
+women	B
+and	O
+35	O
+men	B
+between	O
++	O
+1	O
+.	O
+010	O
+and	O
++	O
+1	O
+.	O
+980	O
+)	O
+and	O
+sample	O
+size	O
+was	O
+adjusted	O
+for	O
+normal	O
+sex	O
+and	O
+height	O
+SDS	O
+distribution	O
+.	O
+
+Height	O
+and	O
+weight	O
+were	O
+recorded	O
+in	O
+the	O
+morning	O
+by	O
+a	O
+single	O
+observer	O
+.	O
+
+Height	O
+was	O
+measured	O
+with	O
+a	O
+Harpenden	O
+stadiometer	O
+.	O
+
+Four	O
+millilitres	O
+of	O
+peripheral	O
+venous	O
+blood	O
+were	O
+drawn	O
+into	O
+EDTA	O
+-	O
+containing	O
+tubes	O
+for	O
+molecular	O
+genetic	O
+analysis	O
+.	O
+
+Genomic	O
+DNA	O
+study	O
+
+Genomic	O
+DNA	O
+was	O
+obtained	O
+from	O
+peripheral	O
+blood	O
+following	O
+the	O
+method	O
+described	O
+by	O
+Lahiri	O
+and	O
+Nurnberger	O
+.	O
+24	O
+DNA	O
+was	O
+amplified	O
+by	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+using	O
+a	O
+nested	O
+strategy	O
+.	O
+
+Briefly	O
+,	O
+50	O
+ng	O
+of	O
+genomic	O
+DNA	O
+were	O
+added	O
+to	O
+a	O
+10	O
+micro	O
+l	O
+reaction	O
+mixture	O
+of	O
+1	O
+mm	O
+Mg	O
+(	O
+OAc	O
+)	O
+2	O
+,	O
+0	O
+.	O
+6	O
+mm	O
+dNTPs	O
+,	O
+0	O
+.	O
+3	O
+micro	O
+m	O
+of	O
+each	O
+primer	O
+,	O
+and	O
+0	O
+.	O
+4	O
+U	O
+r	O
+Tth	O
+DNA	O
+polymerase	O
+XL	O
+(	O
+Applied	O
+Biosystems	O
+,	O
+Foster	O
+City	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+The	O
+sense	O
+and	O
+antisense	O
+primers	O
+used	O
+corresponded	O
+to	O
+nucleotides	O
+4156	O
+-	O
+5	O
+'	O
+ACGGTCCGCCACTACGCCCA	O
+-	O
+3	O
+'	O
+and	O
+the	O
+complement	O
+of	O
+6948	O
+-	O
+5	O
+'	O
+TGCAGTGAGCCAAGATTGTG	O
+-	O
+3	O
+'	O
+of	O
+the	O
+GH	O
+gene	O
+cluster	O
+.	O
+6	O
+The	O
+PCR	O
+reaction	O
+mix	O
+was	O
+denatured	O
+for	O
+5	O
+min	O
+at	O
+94	O
+degrees	O
+C	O
+and	O
+cycled	O
+40	O
+times	O
+(	O
+94	O
+degrees	O
+C	O
+,	O
+1	O
+min	O
+;	O
+72	O
+degrees	O
+C	O
+,	O
+3	O
+min	O
+30	O
+s	O
+)	O
+followed	O
+by	O
+a	O
+7	O
+-	O
+min	O
+extension	O
+at	O
+72	O
+degrees	O
+C	O
+.	O
+
+The	O
+resulting	O
+GH1	O
+PCR	O
+products	O
+(	O
+2893	O
+bp	O
+)	O
+were	O
+used	O
+as	O
+templates	O
+for	O
+five	O
+nested	O
+reactions	O
+(	O
+AN	O
+,	O
+BL	O
+,	O
+CK	O
+,	O
+DI	O
+,	O
+FP	O
+)	O
+,	O
+carried	O
+out	O
+as	O
+follows	O
+:	O
+1	O
+micro	O
+l	O
+of	O
+each	O
+GH1	O
+PCR	O
+product	O
+was	O
+added	O
+to	O
+a	O
+20	O
+micro	O
+l	O
+reaction	O
+mixture	O
+of	O
+1	O
+.	O
+5	O
+mm	O
+MgCl2	O
+,	O
+0	O
+.	O
+2	O
+mm	O
+dNTPs	O
+,	O
+0	O
+.	O
+3	O
+micro	O
+m	O
+of	O
+each	O
+primer	O
+and	O
+0	O
+.	O
+4	O
+U	O
+Eco	O
+Taq	O
+DNA	O
+polymerase	O
+(	O
+Ecogen	O
+S	O
+.	O
+R	O
+.	O
+L	O
+.	O
+,	O
+Barcelona	O
+,	O
+Spain	O
+)	O
+.	O
+
+Reaction	O
+mixtures	O
+were	O
+denatured	O
+for	O
+5	O
+min	O
+at	O
+94	O
+degrees	O
+C	O
+,	O
+cycled	O
+40	O
+times	O
+(	O
+94	O
+degrees	O
+C	O
+,	O
+1	O
+min	O
+;	O
+58	O
+degrees	O
+C	O
+,	O
+1	O
+min	O
+;	O
+and	O
+72	O
+degrees	O
+C	O
+,	O
+1	O
+min	O
+)	O
+,	O
+followed	O
+by	O
+a	O
+7	O
+-	O
+min	O
+extension	O
+at	O
+72	O
+degrees	O
+C	O
+.	O
+
+Sense	O
+and	O
+antisense	O
+primers	O
+were	O
+as	O
+follows	O
+:	O
+
+Sequencing	O
+from	O
+both	O
+ends	O
+was	O
+performed	O
+by	O
+the	O
+dideoxy	O
+method	O
+using	O
+ABI	O
+PRISM	O
+BigDye	O
+Terminator	O
+version	O
+3	O
+.	O
+1	O
+Cycle	O
+Sequencing	O
+Kit	O
+(	O
+Applied	O
+Biosystems	O
+,	O
+Foster	O
+City	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+GH1	O
+gene	O
+nucleotide	O
+sequence	O
+published	O
+by	O
+Chen	O
+et	O
+al	O
+.	O
+6	O
+was	O
+used	O
+as	O
+control	O
+.	O
+
+For	O
+each	O
+DNA	O
+,	O
+the	O
+five	O
+segments	O
+from	O
+the	O
+nested	O
+PCR	O
+were	O
+assembled	O
+with	O
+the	O
+SeqEscape	O
+programme	O
+(	O
+Applied	O
+Biosystems	O
+)	O
+and	O
+interpretation	O
+was	O
+made	O
+visually	O
+and	O
+simultaneously	O
+by	O
+two	O
+observers	O
+.	O
+
+Antisense	O
+sequencing	O
+was	O
+performed	O
+to	O
+confirm	O
+each	O
+nucleotide	O
+sequence	O
+change	O
+up	O
+to	O
+the	O
+establishment	O
+of	O
+the	O
+more	O
+frequent	O
+SNP	O
+map	O
+(	O
+frequency	O
+over	O
+1	O
+%	O
+)	O
+,	O
+whereas	O
+less	O
+frequent	O
+single	O
+or	O
+multiple	O
+nucleotide	O
+changes	O
+were	O
+reconfirmed	O
+in	O
+each	O
+DNA	O
+by	O
+antisense	O
+sequence	O
+and	O
+resequencing	O
+after	O
+a	O
+new	O
+nested	O
+PCR	O
+from	O
+original	O
+DNA	O
+was	O
+performed	O
+.	O
+
+Single	O
+nucleotide	O
+polymorphism	O
+(	O
+SNP	O
+)	O
+genotyping	O
+
+The	O
+sequences	O
+for	O
+the	O
+five	O
+genes	O
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+the	O
+GH	O
+cluster	O
+identified	O
+by	O
+Chen	O
+et	O
+al	O
+.	O
+6	O
+and	O
+reported	O
+as	O
+the	O
+GI	O
+sequence	O
+183148	O
+were	O
+aligned	O
+using	O
+the	O
+Multalin	O
+program	O
+.	O
+25	O
+SNPs	O
+and	O
+other	O
+sequence	O
+changes	O
+identified	O
+were	O
+indicated	O
+using	O
+their	O
+position	O
+corresponding	O
+to	O
+GH1	O
+.	O
+
+Genotypes	O
+were	O
+deduced	O
+by	O
+the	O
+combination	O
+of	O
+genetic	O
+variation	O
+at	O
+the	O
+polymorphic	O
+positions	O
+.	O
+
+Statistical	O
+analysis	O
+
+Standardized	O
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+was	O
+investigated	O
+for	O
+normal	O
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+(	O
+Kolmogorov	O
+-	O
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+test	O
+:	O
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+=	O
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+,	O
+P	O
+=	O
+0	O
+.	O
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+)	O
+.	O
+
+Hardy	O
+-	O
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+tested	O
+for	O
+SNPs	O
+presenting	O
+three	O
+alternate	O
+genotypes	O
+according	O
+to	O
+standard	O
+procedures	O
+using	O
+chi	O
+2	O
+-	O
+analysis	O
+.	O
+anova	O
+test	O
+was	O
+applied	O
+to	O
+investigate	O
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+and	O
+combined	O
+SNP	O
+association	O
+with	O
+adult	O
+height	O
+SDS	O
+;	O
+significance	O
+assessment	O
+was	O
+adjusted	O
+for	O
+multiple	O
+testing	O
+using	O
+Fisher	O
+'	O
+s	O
+PLSD	O
+test	O
+setting	O
+Pcritical	O
+=	O
+0	O
+.	O
+05	O
+or	O
+the	O
+Bonferroni	O
+-	O
+Dunn	O
+test	O
+setting	O
+Pcritical	O
+=	O
+0	O
+.	O
+05	O
+/	O
+n	O
+(	O
+n	O
+=	O
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+comparisons	O
+carried	O
+out	O
+)	O
+.	O
+
+Stepwise	O
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+analysis	O
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+applied	O
+to	O
+predict	O
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+contribution	O
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+SNPs	O
+to	O
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+.	O
+
+Statview	O
+4	O
+.	O
+5	O
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+(	O
+Abacus	O
+Concepts	O
+Inc	O
+.	O
+,	O
+Berkeley	O
+,	O
+CA	O
+,	O
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+)	O
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+used	O
+for	O
+statistical	O
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+.	O
+
+Results	O
+
+GH1	O
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+
+GH1	O
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+-	O
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+a	O
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+54	O
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+
+Twenty	O
+-	O
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+
+SNPs	O
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+(	O
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+,	O
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+,	O
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+,	O
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+)	O
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+(	O
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+
+Twenty	O
+-	O
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+(	O
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+
+These	O
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+)	O
+,	O
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+
+GH1	O
+-	O
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+
+A	O
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+paralogues	O
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+-	O
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+(	O
+Fig	O
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+)	O
+.	O
+
+This	O
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+(	O
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+)	O
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+.	O
+
+Among	O
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+(	O
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+,	O
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+(	O
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+=	O
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+=	O
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+=	O
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+
+Equivalence	O
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+Equivalence	O
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+
+The	O
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+,	O
+12	O
+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+,	O
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+
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+Associations	O
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+(	O
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+=	O
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+=	O
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+)	O
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+
+Three	O
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+,	O
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+)	O
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+)	O
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+
+Subjects	O
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+(	O
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+=	O
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+,	O
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+,	O
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+)	O
+.	O
+
+P16	O
+and	O
+P17	O
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+in	O
+linkage	O
+disequilibrium	O
+(	O
+LD	O
+)	O
+(	O
+r2	O
+=	O
+0	O
+.	O
+831	O
+)	O
+,	O
+while	O
+P25	O
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+by	O
+six	O
+subjects	O
+homozygous	O
+at	O
+P16	O
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+P17	O
+.	O
+
+GH1	O
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+genotypes	O
+were	O
+defined	O
+by	O
+genetic	O
+variation	O
+in	O
+the	O
+25	O
+polymorphic	O
+positions	O
+.	O
+
+We	O
+found	O
+163	O
+different	O
+combinations	O
+.	O
+
+Only	O
+two	O
+genotypes	O
+presented	O
+a	O
+frequency	O
+over	O
+5	O
+%	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+Height	O
+SDS	O
+in	O
+the	O
+two	O
+more	O
+frequent	O
+genotypes	O
+did	O
+not	O
+differ	O
+significantly	O
+and	O
+covered	O
+the	O
+whole	O
+height	O
+range	O
+.	O
+
+Genotype	O
+1	O
+presented	O
+four	O
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+variations	O
+and	O
+Genotype	O
+2	O
+was	O
+the	O
+corresponding	O
+homozygous	O
+genotype	O
+.	O
+
+Heterozygous	O
+positions	O
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+to	O
+SNPs	O
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+the	O
+highest	O
+frequency	O
+variation	O
+(	O
+4886	O
+(	O
+P4	O
+)	O
+,	O
+5107	O
+(	O
+P7	O
+)	O
+,	O
+5157	O
+(	O
+P10	O
+)	O
+and	O
+6331	O
+(	O
+P24	O
+)	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+DNAs	O
+exhibited	O
+a	O
+different	O
+genotype	O
+in	O
+each	O
+of	O
+129	O
+subjects	O
+(	O
+46	O
+.	O
+4	O
+%	O
+)	O
+.	O
+
+The	O
+11	O
+SNPs	O
+found	O
+in	O
+the	O
+promoter	O
+region	O
+(	O
+Table	O
+1	O
+)	O
+were	O
+grouped	O
+in	O
+94	O
+genotypes	O
+and	O
+analysed	O
+for	O
+association	O
+with	O
+adult	O
+height	O
+SDS	O
+.	O
+
+The	O
+four	O
+more	O
+frequent	O
+combinations	O
+are	O
+listed	O
+in	O
+Table	O
+4	O
+:	O
+height	O
+SDS	O
+of	O
+these	O
+four	O
+genotypes	O
+did	O
+not	O
+differ	O
+statistically	O
+although	O
+Genotype	O
+3	O
+tended	O
+to	O
+have	O
+a	O
+shorter	O
+height	O
+.	O
+
+Genotype	O
+3	O
+differed	O
+from	O
+Genotype	O
+1	O
+in	O
+the	O
+SNP	O
+located	O
+at	O
+position	O
+5089	O
+(	O
+P6	O
+)	O
+,	O
+corresponding	O
+to	O
+Pit	O
+1	O
+proximal	O
+responsive	O
+element	O
+for	O
+GH1	O
+gene	O
+promoter	O
+.	O
+
+Genotype	O
+4	O
+is	O
+heterozygous	O
+at	O
+positions	O
+4856	O
+(	O
+P2	O
+)	O
+,	O
+4863	O
+(	O
+P3	O
+)	O
+and	O
+5107	O
+(	O
+P7	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+19	O
+%	O
+of	O
+cases	O
+exhibited	O
+a	O
+genotype	O
+in	O
+the	O
+promoter	O
+region	O
+carried	O
+by	O
+only	O
+one	O
+subject	O
+.	O
+
+Combination	O
+of	O
+the	O
+three	O
+SNPs	O
+in	O
+the	O
+5	O
+'	O
+UTR	O
+region	O
+of	O
+GH1	O
+gene	O
+resulted	O
+in	O
+five	O
+different	O
+genotypes	O
+.	O
+
+SNPs	O
+at	O
+positions	O
+5178	O
+(	O
+P12	O
+)	O
+and	O
+5187	O
+(	O
+P13	O
+)	O
+were	O
+in	O
+LD	O
+(	O
+r2	O
+=	O
+0	O
+.	O
+88	O
+)	O
+.	O
+
+Mean	O
+height	O
+SDS	O
+comparison	O
+among	O
+these	O
+genotypes	O
+was	O
+not	O
+statistically	O
+significant	O
+,	O
+although	O
+mean	O
+height	O
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+alternate	O
+nucleotide	O
+carriers	O
+at	O
+position	O
+5178	O
+(	O
+P12	O
+)	O
+tended	O
+to	O
+be	O
+shorter	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+An	O
+anova	O
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+investigate	O
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+.	O
+
+SNPs	O
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+(	O
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+)	O
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+)	O
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+LD	O
+(	O
+r2	O
+=	O
+0	O
+.	O
+83	O
+)	O
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+/	O
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+for	O
+these	O
+SNPs	O
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+associated	O
+with	O
+taller	O
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+(	O
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+above	O
+)	O
+.	O
+
+SNP	O
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+position	O
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+(	O
+P25	O
+)	O
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+the	O
+expected	O
+height	O
+SDS	O
+for	O
+individual	O
+carriers	O
+of	O
+the	O
+G	O
+allele	O
+at	O
+5089	O
+(	O
+P6	O
+)	O
+SNP	O
+as	O
+shown	O
+in	O
+Fig	O
+.	O
+
+2	O
+(	O
+d	O
+)	O
+:	O
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+6358	O
+(	O
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+)	O
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+than	O
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+,	O
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+subjects	O
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+GG	O
+/	O
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+corresponding	O
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+TT	O
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+(	O
+P	O
+=	O
+0	O
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+)	O
+,	O
+suggesting	O
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+
+Analysis	O
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+variant	O
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+
+None	O
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+,	O
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+)	O
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+only	O
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+
+In	O
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+,	O
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+(	O
+0	O
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+000	O
++	O
+/	O
+-	O
+0	O
+.	O
+987	O
+,	O
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+-	O
+1	O
+.	O
+930	O
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++	O
+1	O
+.	O
+870	O
+)	O
+did	O
+not	O
+differ	O
+from	O
+that	O
+of	O
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+278	O
+controls	O
+(	O
+-	O
+0	O
+.	O
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++	O
+/	O
+-	O
+1	O
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+-	O
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++	O
+1	O
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+980	O
+)	O
+.	O
+
+Analysis	O
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+(	O
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+(	O
+Fig	O
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+)	O
+.	O
+
+Only	O
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+sequence	O
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+(	O
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+-	O
+1	O
+.	O
+500	O
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+-	O
+2	O
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+)	O
+(	O
+Table	O
+2	O
+)	O
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+(	O
+4979	O
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+)	O
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+(	O
+5300	O
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+Predicted	O
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+In	O
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+)	O
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+,	O
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+=	O
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+,	O
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+=	O
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+)	O
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+-	O
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++	O
+/	O
+-	O
+0	O
+.	O
+031	O
+,	O
+-	O
+0	O
+.	O
+693	O
++	O
+/	O
+-	O
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+350	O
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+-	O
+0	O
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+489	O
++	O
+/	O
+-	O
+0	O
+.	O
+265	O
+,	O
+respectively	O
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+Mean	O
++	O
+/	O
+-	O
+SE	O
+)	O
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+/	O
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+/	O
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++	O
+1	O
+.	O
+094	O
++	O
+/	O
+-	O
+0	O
+.	O
+456	O
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++	O
+1	O
+.	O
+184	O
++	O
+/	O
+-	O
+0	O
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+,	O
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+)	O
+.	O
+
+Discussion	O
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+Genetic	O
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+-	O
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+,	O
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+-	O
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+,	O
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+-	O
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+patients	B
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+/	O
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+before	O
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+adult	O
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+9	O
+,	O
+11	O
+,	O
+12	O
+Our	O
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+the	O
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+in	O
+individuals	O
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+-	O
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++	O
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+
+Height	O
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+A	O
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+,	O
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+Our	O
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+,	O
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+More	O
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+,	O
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+.	O
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+,	O
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+would	O
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+15	O
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+
+Our	O
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+study	O
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++	O
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+/	O
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+/	O
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+)	O
+.	O
+
+The	O
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+,	O
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+=	O
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+,	O
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+,	O
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+
+These	O
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+
+Three	O
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+
+Only	O
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+,	O
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+.	O
+
+Our	O
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+
+As	O
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+,	O
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+,	O
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+,	O
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+Pit	O
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+,	O
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+/	O
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+/	O
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+(	O
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+.	O
+
+The	O
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+density	O
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+conversion	O
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+any	O
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+(	O
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+)	O
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+.	O
+9	O
+,	O
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+,	O
+28	O
+Alignment	O
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+the	O
+25	O
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+the	O
+other	O
+GH1	O
+gene	O
+paralogues	O
+demonstrated	O
+in	O
+our	O
+results	O
+that	O
+this	O
+mechanism	O
+is	O
+possible	O
+for	O
+64	O
+%	O
+of	O
+SNPs	O
+.	O
+
+Familial	O
+SNP	O
+transmission	O
+pattern	O
+analysis	O
+will	O
+be	O
+of	O
+interest	O
+to	O
+support	O
+the	O
+hypothesis	O
+of	O
+GH	O
+gene	O
+recombination	O
+.	O
+
+In	O
+addition	O
+,	O
+29	O
+of	O
+307	O
+individuals	O
+(	O
+9	O
+.	O
+4	O
+%	O
+)	O
+bore	O
+additional	O
+GH1	O
+sequence	O
+changes	O
+with	O
+frequencies	O
+under	O
+1	O
+%	O
+.	O
+
+As	O
+for	O
+SNPs	O
+,	O
+they	O
+are	O
+located	O
+along	O
+the	O
+whole	O
+gene	O
+with	O
+higher	O
+density	O
+in	O
+the	O
+promoter	O
+and	O
+5	O
+'	O
+UTR	O
+regions	O
+.	O
+
+Interestingly	O
+,	O
+intron	O
+3	O
+and	O
+exon	O
+5	O
+present	O
+several	O
+of	O
+these	O
+less	O
+frequent	O
+changes	O
+.	O
+
+Intron	O
+3	O
+has	O
+been	O
+shown	O
+to	O
+carry	O
+the	O
+majority	O
+of	O
+single	O
+nucleotide	O
+mutations	O
+causing	O
+the	O
+dominant	O
+form	O
+of	O
+GH	O
+deficiency	O
+.	O
+3	O
+The	O
+two	O
+single	O
+nucleotide	O
+changes	O
+detected	O
+in	O
+intron	O
+3	O
+(	O
+R15	O
+at	O
+6056	O
+and	O
+R16	O
+at	O
+6061	O
+)	O
+are	O
+in	O
+perfect	O
+LD	O
+(	O
+r2	O
+=	O
+1	O
+.	O
+0	O
+)	O
+and	O
+located	O
+within	O
+the	O
+enhancer	O
+splice	O
+site	O
+element	O
+(	O
+ESE	O
+)	O
+described	O
+by	O
+Ryther	O
+et	O
+al	O
+.	O
+29	O
+,	O
+30	O
+Studies	O
+in	O
+additional	O
+normal	O
+or	O
+growth	O
+-	O
+retarded	O
+populations	O
+will	O
+permit	O
+description	O
+of	O
+their	O
+possible	O
+clinical	O
+implications	O
+.	O
+
+Five	O
+single	O
+nucleotide	O
+changes	O
+are	O
+located	O
+in	O
+exon	O
+5	O
+;	O
+of	O
+these	O
+five	O
+,	O
+three	O
+predict	O
+an	O
+amino	O
+acid	O
+change	O
+,	O
+and	O
+one	O
+of	O
+the	O
+three	O
+(	O
+Ile179Met	O
+)	O
+has	O
+been	O
+described	O
+by	O
+Lewis	O
+et	O
+al	O
+.	O
+27	O
+in	O
+a	O
+paediatric	O
+patient	B
+with	O
+familial	O
+short	O
+stature	O
+and	O
+the	O
+other	O
+two	O
+,	O
+as	O
+yet	O
+undescribed	O
+,	O
+are	O
+contiguous	O
+in	O
+a	O
+single	O
+individual	O
+(	O
+Pro133Hys	O
+and	O
+Arg134Leu	O
+)	O
+.	O
+
+Polynucleotide	O
+changes	O
+are	O
+mostly	O
+located	O
+in	O
+the	O
+promoter	O
+region	O
+corresponding	O
+to	O
+the	O
+VDR	O
+/	O
+RA	O
+/	O
+T3	O
+response	O
+element	O
+.	O
+
+As	O
+for	O
+frequent	O
+SNPs	O
+,	O
+the	O
+majority	O
+of	O
+the	O
+sequence	O
+changes	O
+with	O
+frequencies	O
+under	O
+1	O
+%	O
+may	O
+have	O
+been	O
+generated	O
+by	O
+recombination	O
+within	O
+the	O
+GH	O
+gene	O
+cluster	O
+as	O
+19	O
+of	O
+24	O
+(	O
+79	O
+%	O
+)	O
+may	O
+correspond	O
+to	O
+one	O
+or	O
+more	O
+of	O
+the	O
+GH1	O
+gene	O
+paralogues	O
+.	O
+
+Our	O
+results	O
+now	O
+show	O
+the	O
+diversity	O
+and	O
+complexity	O
+of	O
+SNP	O
+genotypes	O
+,	O
+as	O
+previously	O
+highlighted	O
+by	O
+other	O
+authors9	O
+,	O
+10	O
+,	O
+12	O
+,	O
+21	O
+in	O
+a	O
+normal	O
+adult	O
+height	O
+control	O
+population	O
+.	O
+
+Our	O
+initial	O
+aim	O
+when	O
+designing	O
+the	O
+present	O
+study	O
+was	O
+to	O
+establish	O
+the	O
+map	O
+of	O
+GH1	O
+gene	O
+SNPs	O
+in	O
+our	O
+adult	O
+control	O
+population	O
+with	O
+heights	O
+normally	O
+distributed	O
+within	O
+the	O
+entire	O
+normal	O
+range	O
+for	O
+further	O
+comparison	O
+with	O
+genotypes	O
+in	O
+our	O
+paediatric	O
+population	O
+with	O
+growth	O
+delay	O
+,	O
+variable	O
+response	O
+to	O
+GH	O
+secretion	O
+tests	O
+and	O
+adequate	O
+response	O
+to	O
+GH	O
+therapy	O
+.	O
+
+Analysis	O
+of	O
+SNP	O
+association	O
+with	O
+adult	O
+height	O
+was	O
+subsequently	O
+performed	O
+to	O
+establish	O
+a	O
+body	O
+of	O
+knowledge	O
+useful	O
+for	O
+comparing	O
+patient	B
+genotypes	O
+and	O
+phenotypes	O
+.	O
+
+This	O
+analysis	O
+was	O
+first	O
+performed	O
+in	O
+controls	O
+bearing	O
+only	O
+frequent	O
+SNPs	O
+(	O
+90	O
+.	O
+5	O
+%	O
+of	O
+the	O
+total	O
+population	O
+)	O
+.	O
+
+We	O
+demonstrate	O
+that	O
+the	O
+four	O
+SNPs	O
+with	O
+the	O
+highest	O
+allelic	O
+variation	O
+frequencies	O
+(	O
+P4	O
+,	O
+P7	O
+,	O
+P10	O
+and	O
+P24	O
+)	O
+do	O
+not	O
+significantly	O
+contribute	O
+to	O
+adult	O
+height	O
+determination	O
+,	O
+with	O
+the	O
+heterozygous	O
+genotype	O
+being	O
+the	O
+most	O
+frequent	O
+followed	O
+by	O
+the	O
+corresponding	O
+homozygous	O
+genotype	O
+in	O
+the	O
+whole	O
+sequence	O
+,	O
+and	O
+heights	O
+are	O
+normally	O
+distributed	O
+over	O
+the	O
+entire	O
+height	O
+range	O
+.	O
+
+The	O
+third	O
+most	O
+frequent	O
+combined	O
+genotype	O
+in	O
+the	O
+promoter	O
+region	O
+in	O
+our	O
+population	O
+presented	O
+,	O
+in	O
+addition	O
+,	O
+in	O
+heterozygosity	O
+,	O
+the	O
+SNP	O
+at	O
+P6	O
+in	O
+the	O
+sequence	O
+regulated	O
+by	O
+Pit	O
+1	O
+and	O
+although	O
+mean	O
+height	O
+of	O
+individuals	O
+(	O
+6	O
+.	O
+1	O
+%	O
+)	O
+bearing	O
+this	O
+genotype	O
+was	O
+around	O
+-	O
+0	O
+.	O
+5	O
+SDS	O
+,	O
+this	O
+was	O
+not	O
+statistically	O
+significant	O
+.	O
+
+Analysis	O
+of	O
+single	O
+SNP	O
+genotype	O
+association	O
+with	O
+adult	O
+height	O
+yielded	O
+few	O
+clues	O
+as	O
+to	O
+the	O
+contribution	O
+of	O
+GH1	O
+gene	O
+variation	O
+to	O
+adult	O
+height	O
+determination	O
+.	O
+
+Only	O
+three	O
+SNPs	O
+(	O
+P16	O
+,	O
+P17	O
+and	O
+P25	O
+)	O
+,	O
+present	O
+with	O
+low	O
+frequency	O
+and	O
+only	O
+in	O
+heterozygous	O
+state	O
+,	O
+were	O
+individually	O
+significantly	O
+associated	O
+with	O
+taller	O
+stature	O
+and	O
+none	O
+was	O
+individually	O
+associated	O
+with	O
+shorter	O
+stature	O
+.	O
+
+P16	O
+and	O
+P17	O
+(	O
+in	O
+LD	O
+,	O
+r2	O
+=	O
+0	O
+.	O
+83	O
+)	O
+are	O
+located	O
+in	O
+intron	O
+1	O
+and	O
+P25	O
+in	O
+intron	O
+4	O
+.	O
+
+The	O
+resulting	O
+sequence	O
+for	O
+the	O
+presence	O
+of	O
+P16	O
+and	O
+P17	O
+corresponded	O
+to	O
+the	O
+paralogue	O
+GH2	O
+and	O
+generated	O
+a	O
+responsive	O
+element	O
+for	O
+a	O
+core	O
+-	O
+binding	O
+protein	O
+(	O
+Matinspector	O
+Programme	O
+,	O
+Geometrix	O
+Software	O
+GmbH	O
+,	O
+M	O
+u	O
+nchen	O
+,	O
+Germany	O
+)	O
+with	O
+three	O
+Kruppel	O
+-	O
+type	O
+zinc	O
+fingers	O
+which	O
+could	O
+increase	O
+the	O
+efficacy	O
+of	O
+GH1	O
+gene	O
+transcription	O
+;	O
+31	O
+,	O
+32	O
+moreover	O
+,	O
+Kruppel	O
+-	O
+like	O
+proteins	O
+have	O
+recently	O
+been	O
+described	O
+in	O
+the	O
+brain	O
+.	O
+33	O
+Stepwise	O
+regression	O
+analysis	O
+demonstrated	O
+that	O
+P17	O
+and	O
+P25	O
+contribute	O
+,	O
+separately	O
+,	O
+to	O
+an	O
+increase	O
+of	O
+almost	O
+1	O
+.	O
+0	O
+height	O
+SDS	O
+.	O
+
+P16	O
+and	O
+P17	O
+had	O
+been	O
+described	O
+by	O
+Adkins	O
+et	O
+al	O
+.	O
+21	O
+although	O
+they	O
+found	O
+no	O
+association	O
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+fetal	O
+growth	O
+,	O
+whereas	O
+P25	O
+had	O
+not	O
+previously	O
+been	O
+described	O
+.	O
+
+The	O
+mechanisms	O
+by	O
+which	O
+they	O
+may	O
+determine	O
+taller	O
+final	O
+height	O
+should	O
+be	O
+established	O
+by	O
+in	O
+vitro	O
+studies	O
+analysing	O
+GH1	O
+gene	O
+transcription	O
+and	O
+GH	O
+protein	O
+translation	O
+efficiencies	O
+.	O
+
+Analysis	O
+of	O
+interaction	O
+effect	O
+between	O
+SNPs	O
+detected	O
+that	O
+variation	O
+at	O
+P25	O
+masked	O
+an	O
+effect	O
+of	O
+P6	O
+.	O
+
+Individuals	O
+homozygous	O
+at	O
+P25	O
+(	O
+TT	O
+)	O
+present	O
+a	O
+significant	O
+association	O
+between	O
+P6	O
+genotype	O
+and	O
+height	O
+with	O
+the	O
+homozygous	O
+alternate	O
+genotype	O
+at	O
+P6	O
+(	O
+GG	O
+)	O
+being	O
+associated	O
+with	O
+shorter	O
+stature	O
+.	O
+
+This	O
+was	O
+further	O
+confirmed	O
+in	O
+the	O
+subpopulation	O
+of	O
+29	O
+individuals	O
+bearing	O
+rare	O
+SNPs	O
+who	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+heterozygous	O
+change	O
+at	O
+P25	O
+,	O
+presented	O
+significantly	O
+shorter	O
+stature	O
+in	O
+the	O
+heterozygous	O
+alternate	O
+nucleotide	O
+change	O
+at	O
+P6	O
+(	O
+AG	O
+)	O
+.	O
+
+P6	O
+,	O
+located	O
+at	O
+Pit	O
+1	O
+proximal	O
+responsive	O
+element	O
+of	O
+the	O
+GH1	O
+gene	O
+promoter	O
+,	O
+was	O
+first	O
+described	O
+by	O
+Wagner	O
+et	O
+al	O
+.	O
+10	O
+and	O
+Giordano	O
+et	O
+al	O
+.	O
+9	O
+and	O
+further	O
+by	O
+Horan	O
+et	O
+al	O
+.	O
+12	O
+Six	O
+of	O
+nine	O
+GH1	O
+gene	O
+promoter	O
+haplotypes	O
+bearing	O
+the	O
+alternate	O
+G	O
+at	O
+P6	O
+presented	O
+lower	O
+transcriptional	O
+activities	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+(	O
+EMSA	O
+)	O
+detected	O
+differential	O
+protein	O
+binding	O
+strength	O
+,	O
+although	O
+in	O
+vitro	O
+studies	O
+were	O
+unable	O
+to	O
+identify	O
+this	O
+SNP	O
+as	O
+a	O
+major	O
+determinant	O
+of	O
+GH1	O
+gene	O
+expression	O
+level	O
+.	O
+12	O
+A	O
+recent	O
+study	O
+from	O
+Giordano	O
+et	O
+al	O
+.	O
+34	O
+has	O
+shown	O
+a	O
+twofold	O
+reduced	O
+luciferase	O
+activity	O
+for	O
+the	O
+G	O
+nucleotide	O
+bearing	O
+promoter	O
+haplotype	O
+in	O
+transfected	O
+rat	B
+pituitary	O
+cells	O
+.	O
+
+Genotypes	O
+at	O
+P6	O
+had	O
+also	O
+been	O
+associated	O
+with	O
+decreased	O
+breast	O
+cancer	O
+risk	O
+through	O
+its	O
+association	O
+with	O
+lower	O
+GH	O
+secretion	O
+and	O
+IGF	O
+-	O
+I	O
+circulating	O
+levels	O
+.	O
+16	O
+,	O
+17	O
+
+In	O
+our	O
+results	O
+,	O
+GH1	O
+gene	O
+polymorphic	O
+structural	O
+variation	O
+accounted	O
+for	O
+only	O
+6	O
+.	O
+2	O
+%	O
+of	O
+adult	O
+height	O
+determination	O
+in	O
+the	O
+entire	O
+adult	O
+population	O
+studied	O
+and	O
+genome	O
+-	O
+wide	O
+linkage	O
+analysis	O
+of	O
+stature	O
+in	O
+multiple	O
+populations	O
+revealed	O
+no	O
+linkage	O
+with	O
+chromosome	O
+17	O
+GH	O
+gene	O
+cluster	O
+.	O
+2	O
+,	O
+35	O
+As	O
+only	O
+some	O
+of	O
+the	O
+less	O
+frequent	O
+SNPs	O
+are	O
+statistically	O
+associated	O
+with	O
+height	O
+,	O
+and	O
+in	O
+view	O
+of	O
+the	O
+high	O
+density	O
+of	O
+SNPs	O
+,	O
+our	O
+study	O
+may	O
+be	O
+hampered	O
+by	O
+selection	O
+bias36	O
+and	O
+would	O
+ideally	O
+have	O
+required	O
+a	O
+wider	O
+sampling	O
+of	O
+some	O
+2	O
+000	O
+individuals	O
+;	O
+however	O
+,	O
+this	O
+was	O
+a	O
+highly	O
+laborious	O
+strategy	O
+when	O
+the	O
+complete	O
+sequencing	O
+technique	O
+is	O
+applied	O
+.	O
+
+The	O
+high	O
+density	O
+of	O
+SNPs	O
+and	O
+their	O
+proximity	O
+hamper	O
+other	O
+genotyping	O
+strategies	O
+for	O
+rapid	O
+determination	O
+of	O
+the	O
+complete	O
+GH1	O
+SNP	O
+map	O
+in	O
+large	O
+control	O
+and	O
+patient	B
+populations	O
+.	O
+
+Individual	O
+SNP	O
+associations	O
+with	O
+height	O
+or	O
+other	O
+GH	O
+secretion	O
+-	O
+related	O
+phenotypic	O
+traits	O
+will	O
+require	O
+further	O
+confirmation	O
+by	O
+studies	O
+in	O
+larger	O
+populations	O
+and	O
+by	O
+in	O
+vitro	O
+functional	O
+studies	O
+.	O
+
+In	O
+conclusion	O
+,	O
+our	O
+study	O
+established	O
+the	O
+GH1	O
+gene	O
+sequence	O
+variation	O
+map	O
+in	O
+an	O
+adult	O
+control	O
+population	O
+with	O
+heights	O
+normally	O
+distributed	O
+within	O
+the	O
+normal	O
+range	O
+.	O
+
+SNPs	O
+and	O
+other	O
+sequence	O
+change	O
+contributions	O
+to	O
+skeletal	O
+growth	O
+as	O
+observed	O
+at	O
+adult	O
+height	O
+demonstrated	O
+that	O
+,	O
+despite	O
+the	O
+high	O
+frequency	O
+of	O
+variation	O
+and	O
+diversity	O
+and	O
+complexity	O
+of	O
+combinations	O
+,	O
+only	O
+some	O
+of	O
+the	O
+less	O
+frequent	O
+SNPs	O
+were	O
+associated	O
+with	O
+taller	O
+stature	O
+(	O
+P17	O
+in	O
+intron	O
+1	O
+and	O
+P25	O
+in	O
+intron	O
+4	O
+)	O
+,	O
+even	O
+masking	O
+the	O
+SNP	O
+contribution	O
+to	O
+a	O
+shorter	O
+one	O
+(	O
+P6	O
+in	O
+the	O
+promoter	O
+and	O
+P12	O
+in	O
+the	O
+5	O
+'	O
+UTR	O
+regions	O
+,	O
+respectively	O
+)	O
+.	O
+
+Systematic	O
+GH1	O
+gene	O
+analysis	O
+in	O
+patients	B
+with	O
+growth	O
+delay	O
+and	O
+suspected	O
+GH	O
+deficiency	O
+/	O
+insufficiency	O
+will	O
+clarify	O
+whether	O
+different	O
+SNP	O
+frequencies	O
+and	O
+/	O
+or	O
+the	O
+presence	O
+of	O
+different	O
+sequence	O
+changes	O
+may	O
+be	O
+associated	O
+with	O
+phenotypes	O
+in	O
+them	O
+.	O
+
+Elevated	O
+Blood	O
+Lead	O
+Levels	O
+of	O
+Children	B
+in	O
+Guiyu	O
+,	O
+an	O
+Electronic	O
+Waste	O
+Recycling	O
+Town	O
+in	O
+China	O
+
+Abstract	O
+
+Background	O
+
+Electronic	O
+waste	O
+(	O
+e	O
+-	O
+waste	O
+)	O
+recycling	O
+has	O
+remained	O
+primitive	O
+in	O
+Guiyu	O
+,	O
+China	O
+,	O
+and	O
+thus	O
+may	O
+contribute	O
+to	O
+the	O
+elevation	O
+of	O
+blood	O
+lead	O
+levels	O
+(	O
+BLLs	O
+)	O
+in	O
+children	B
+living	O
+in	O
+the	O
+local	O
+environment	O
+.	O
+
+Objectives	O
+
+We	O
+compared	O
+the	O
+BLLs	O
+in	O
+children	B
+living	O
+in	O
+the	O
+e	O
+-	O
+waste	O
+recycling	O
+town	O
+of	O
+Guiyu	O
+with	O
+those	O
+living	O
+in	O
+the	O
+neighboring	O
+town	O
+of	O
+Chendian	O
+.	O
+
+Methods	O
+
+We	O
+observed	O
+the	O
+processing	O
+of	O
+e	O
+-	O
+waste	O
+recycling	O
+in	O
+Guiyu	O
+and	O
+studied	O
+BLLs	O
+in	O
+a	O
+cluster	O
+sample	O
+of	O
+226	O
+children	B
+<	O
+6	O
+years	O
+of	O
+age	O
+who	O
+lived	O
+in	O
+Guiyu	O
+and	O
+Chendian	O
+.	O
+
+BLLs	O
+were	O
+determined	O
+with	O
+atomic	O
+absorption	O
+spectrophotometry	O
+.	O
+
+Hemoglobin	O
+(	O
+Hgb	O
+)	O
+and	O
+physical	O
+indexes	O
+(	O
+height	O
+and	O
+weight	O
+,	O
+head	O
+and	O
+chest	O
+circumferences	O
+)	O
+were	O
+also	O
+measured	O
+.	O
+
+Results	O
+
+BLLs	O
+in	O
+165	O
+children	B
+of	O
+Guiyu	O
+ranged	O
+from	O
+4	O
+.	O
+40	O
+to	O
+32	O
+.	O
+67	O
+mu	O
+g	O
+/	O
+dL	O
+with	O
+a	O
+mean	O
+of	O
+15	O
+.	O
+3	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+whereas	O
+BLLs	O
+in	O
+61	O
+children	B
+of	O
+Chendian	O
+were	O
+from	O
+4	O
+.	O
+09	O
+to	O
+23	O
+.	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+with	O
+a	O
+mean	O
+of	O
+9	O
+.	O
+94	O
+mu	O
+g	O
+/	O
+dL	O
+.	O
+
+Statistical	O
+analyses	O
+showed	O
+that	O
+children	B
+living	O
+in	O
+Guiyu	O
+had	O
+significantly	O
+higher	O
+BLLs	O
+compared	O
+with	O
+those	O
+living	O
+in	O
+Chendian	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Of	O
+children	B
+in	O
+Guiyu	O
+,	O
+81	O
+.	O
+8	O
+%	O
+(	O
+135	O
+of	O
+165	O
+)	O
+had	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+compared	O
+with	O
+37	O
+.	O
+7	O
+%	O
+of	O
+children	B
+(	O
+23	O
+of	O
+61	O
+)	O
+in	O
+Chendian	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+observed	O
+a	O
+significant	O
+increasing	O
+trend	O
+in	O
+BLLs	O
+with	O
+increasing	O
+age	O
+in	O
+Guiyu	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+It	O
+appeared	O
+that	O
+there	O
+was	O
+correlation	O
+between	O
+the	O
+BLLs	O
+in	O
+children	B
+and	O
+numbers	O
+of	O
+e	O
+-	O
+waste	O
+workshops	O
+.	O
+
+However	O
+,	O
+no	O
+significant	O
+difference	O
+in	O
+Hgb	O
+level	O
+or	O
+physical	O
+indexes	O
+was	O
+found	O
+between	O
+the	O
+two	O
+towns	O
+.	O
+
+Conclusions	O
+
+The	O
+primitive	O
+e	O
+-	O
+waste	O
+recycling	O
+activities	O
+may	O
+contribute	O
+to	O
+the	O
+elevated	O
+BLLs	O
+in	O
+children	B
+living	O
+in	O
+Guiyu	O
+.	O
+
+Disposal	O
+of	O
+electronic	O
+waste	O
+,	O
+or	O
+e	O
+-	O
+waste	O
+,	O
+is	O
+an	O
+emerging	O
+global	O
+environmental	O
+issue	O
+,	O
+as	O
+these	O
+wastes	O
+have	O
+become	O
+the	O
+most	O
+rapidly	O
+growing	O
+segment	O
+of	O
+the	O
+municipal	O
+waste	O
+stream	O
+in	O
+the	O
+world	O
+[	O
+Dahl	O
+2002	O
+;	O
+Halluite	O
+et	O
+al	O
+.	O
+2005	O
+;	O
+Jang	O
+and	O
+Townsend	O
+2003	O
+;	O
+Schmidt	O
+2002	O
+;	O
+Silicon	O
+Valley	O
+Toxics	O
+Coalition	O
+(	O
+SVTC	O
+)	O
+2001	O
+]	O
+.	O
+
+It	O
+is	O
+reported	O
+that	O
+approximately	O
+500	O
+million	O
+computers	O
+became	O
+obsolete	O
+between	O
+1997	O
+and	O
+2007	O
+in	O
+the	O
+United	O
+States	O
+(	O
+National	O
+Safety	O
+Council	O
+1999	O
+)	O
+.	O
+
+Up	O
+to	O
+80	O
+%	O
+of	O
+e	O
+-	O
+waste	O
+from	O
+the	O
+United	O
+States	O
+has	O
+seeped	O
+into	O
+Asia	O
+and	O
+Africa	O
+(	O
+Johnson	O
+2006	O
+;	O
+Puckett	O
+et	O
+al	O
+.	O
+2002	O
+;	O
+Schmidt	O
+2002	O
+,	O
+2006	O
+;	O
+SVTC	O
+2001	O
+)	O
+.	O
+
+It	O
+is	O
+noteworthy	O
+that	O
+the	O
+United	O
+States	O
+is	O
+the	O
+only	O
+developed	O
+country	O
+today	O
+that	O
+has	O
+not	O
+ratified	O
+the	O
+United	O
+Nations	O
+Basel	O
+Convention	O
+,	O
+which	O
+bans	O
+the	O
+export	O
+of	O
+hazardous	O
+wastes	O
+to	O
+developing	O
+countries	O
+(	O
+United	O
+Nations	O
+Environment	O
+Programme	O
+1992	O
+,	O
+2006	O
+;	O
+USA	O
+Today	O
+2002	O
+)	O
+.	O
+
+Together	O
+with	O
+New	O
+Delhi	O
+in	O
+India	O
+,	O
+Guiyu	O
+in	O
+Shantou	O
+,	O
+Guangdong	O
+Province	O
+,	O
+China	O
+(	O
+Figure	O
+1	O
+)	O
+,	O
+is	O
+one	O
+of	O
+the	O
+popular	O
+destinations	O
+of	O
+e	O
+-	O
+waste	O
+(	O
+Brigden	O
+et	O
+al	O
+.	O
+2005	O
+;	O
+Puckett	O
+et	O
+al	O
+.	O
+2002	O
+)	O
+.	O
+
+Within	O
+a	O
+total	O
+area	O
+of	O
+52	O
+km2	O
+and	O
+local	O
+population	O
+of	O
+132	O
+,	O
+000	O
+(	O
+in	O
+2003	O
+)	O
+,	O
+Guiyu	O
+has	O
+accommodated	O
+millions	O
+of	O
+tons	O
+of	O
+e	O
+-	O
+waste	O
+from	O
+overseas	O
+and	O
+domestic	O
+a	O
+year	O
+.	O
+
+Nearly	O
+60	O
+-	O
+80	O
+%	O
+of	O
+families	O
+in	O
+the	O
+town	O
+have	O
+engaged	O
+in	O
+e	O
+-	O
+waste	O
+recycling	O
+operations	O
+conducted	O
+by	O
+small	O
+scale	O
+family	O
+-	O
+run	O
+workshops	O
+,	O
+with	O
+approximately	O
+100	O
+,	O
+000	O
+migrant	O
+workers	O
+employed	O
+in	O
+processing	O
+e	O
+-	O
+waste	O
+.	O
+
+Because	O
+the	O
+implementation	O
+of	O
+a	O
+clean	O
+and	O
+safe	O
+high	O
+-	O
+tech	O
+recovery	O
+process	O
+was	O
+very	O
+expensive	O
+(	O
+Allsopp	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+,	O
+the	O
+processes	O
+and	O
+techniques	O
+used	O
+during	O
+the	O
+recycling	O
+activities	O
+in	O
+Guiyu	O
+were	O
+very	O
+primitive	O
+.	O
+
+The	O
+result	O
+was	O
+that	O
+many	O
+tons	O
+of	O
+e	O
+-	O
+waste	O
+material	O
+and	O
+process	O
+residues	O
+were	O
+dumped	O
+in	O
+workshops	O
+,	O
+yards	O
+,	O
+roadsides	O
+,	O
+open	O
+fields	O
+,	O
+irrigation	O
+canals	O
+,	O
+riverbanks	O
+,	O
+ponds	O
+,	O
+and	O
+rivers	O
+.	O
+
+Hazardous	O
+chemicals	O
+can	O
+be	O
+released	O
+from	O
+e	O
+-	O
+wastes	O
+through	O
+disposal	O
+or	O
+recycling	O
+processes	O
+,	O
+threatening	O
+the	O
+health	O
+of	O
+local	O
+residents	O
+.	O
+
+Several	O
+studies	O
+have	O
+reported	O
+the	O
+soaring	O
+levels	O
+of	O
+toxic	O
+heavy	O
+metals	O
+and	O
+organic	O
+contaminants	O
+in	O
+samples	O
+of	O
+dust	O
+,	O
+soil	O
+,	O
+river	O
+sediment	O
+,	O
+surface	O
+water	O
+,	O
+and	O
+groundwater	O
+of	O
+Guiyu	O
+(	O
+Brigden	O
+et	O
+al	O
+.	O
+2005	O
+;	O
+Puckett	O
+et	O
+al	O
+.	O
+2002	O
+;	O
+Wang	O
+and	O
+Guo	O
+2006	O
+;	O
+Wang	O
+et	O
+al	O
+.	O
+2005	O
+;	O
+Wong	O
+et	O
+al	O
+.	O
+2006	O
+;	O
+Yu	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Previously	O
+,	O
+we	O
+have	O
+shown	O
+that	O
+the	O
+residents	O
+in	O
+Guiyu	O
+had	O
+high	O
+incidence	O
+of	O
+skin	O
+damage	O
+,	O
+headaches	O
+,	O
+vertigo	O
+,	O
+nausea	O
+,	O
+chronic	O
+gastritis	O
+,	O
+and	O
+gastric	O
+and	O
+duodenal	O
+ulcers	O
+,	O
+all	O
+of	O
+which	O
+may	O
+be	O
+caused	O
+by	O
+the	O
+primitive	O
+recycling	O
+processing	O
+of	O
+e	O
+-	O
+waste	O
+(	O
+Qiu	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Of	O
+many	O
+toxic	O
+heavy	O
+metals	O
+,	O
+lead	O
+is	O
+the	O
+most	O
+widely	O
+used	O
+in	O
+electronic	O
+devices	O
+for	O
+various	O
+purposes	O
+,	O
+resulting	O
+in	O
+a	O
+variety	O
+of	O
+health	O
+hazards	O
+due	O
+to	O
+environmental	O
+contamination	O
+(	O
+Jang	O
+and	O
+Townsend	O
+2003	O
+;	O
+Musson	O
+et	O
+al	O
+.	O
+2006	O
+;	O
+Vann	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Lead	O
+enters	O
+biological	O
+systems	O
+via	O
+food	O
+,	O
+water	O
+,	O
+air	O
+,	O
+and	O
+soil	O
+.	O
+
+Children	B
+are	O
+particularly	O
+vulnerable	O
+to	O
+lead	O
+poisoning	O
+-	O
+-	O
+more	O
+so	O
+than	O
+adults	O
+because	O
+they	O
+absorb	O
+more	O
+lead	O
+from	O
+their	O
+environments	O
+(	O
+Baghurst	O
+et	O
+al	O
+.	O
+1992	O
+;	O
+Grigg	O
+2004	O
+;	O
+Guilarte	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Jain	O
+and	O
+Hu	O
+2006	O
+;	O
+Needleman	O
+2004	O
+;	O
+Safi	O
+et	O
+al	O
+.	O
+2006	O
+;	O
+Wasserman	O
+et	O
+al	O
+.	O
+1998	O
+)	O
+.	O
+
+The	O
+U	O
+.	O
+S	O
+.	O
+
+Centers	O
+for	O
+Disease	O
+Control	O
+and	O
+Prevention	O
+(	O
+CDC	O
+)	O
+defined	O
+elevated	O
+blood	O
+lead	O
+levels	O
+(	O
+BLLs	O
+)	O
+as	O
+those	O
+>	O
+=	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+in	O
+children	B
+<	O
+=	O
+6	O
+years	O
+of	O
+age	O
+(	O
+CDC	O
+1991	O
+)	O
+.	O
+
+Nevertheless	O
+,	O
+studies	O
+have	O
+increasingly	O
+shown	O
+that	O
+low	O
+blood	O
+lead	O
+concentrations	O
+,	O
+even	O
+<	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+were	O
+inversely	O
+associated	O
+with	O
+children	B
+'	O
+s	O
+IQ	O
+scores	O
+and	O
+academic	O
+skills	O
+(	O
+Canfield	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Lanphear	O
+et	O
+al	O
+.	O
+2000	O
+,	O
+2005	O
+;	O
+Nevin	O
+2000	O
+;	O
+Schnaas	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Therefore	O
+,	O
+no	O
+safety	O
+margin	O
+at	O
+existing	O
+exposures	O
+has	O
+been	O
+identified	O
+(	O
+Chiodo	O
+et	O
+al	O
+.	O
+2004	O
+;	O
+Koller	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Considering	O
+the	O
+potential	O
+heavy	O
+metal	O
+contamination	O
+in	O
+the	O
+local	O
+living	O
+environment	O
+of	O
+Guiyu	O
+,	O
+we	O
+hypothesized	O
+that	O
+children	B
+living	O
+in	O
+Guiyu	O
+may	O
+have	O
+elevated	O
+BLLs	O
+and	O
+thus	O
+their	O
+physical	O
+and	O
+mental	O
+development	O
+may	O
+have	O
+been	O
+affected	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+evaluated	O
+the	O
+mean	O
+BLLs	O
+in	O
+children	B
+1	O
+-	O
+6	O
+years	O
+of	O
+age	O
+living	O
+in	O
+Guiyu	O
+and	O
+compared	O
+them	O
+with	O
+those	O
+living	O
+in	O
+the	O
+neighboring	O
+town	O
+of	O
+Chendian	O
+,	O
+where	O
+no	O
+e	O
+-	O
+waste	O
+processing	O
+was	O
+taken	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Geographic	O
+location	O
+and	O
+site	O
+description	O
+
+There	O
+are	O
+28	O
+villages	O
+with	O
+a	O
+total	O
+area	O
+of	O
+52	O
+km2	O
+and	O
+a	O
+resident	O
+population	O
+of	O
+132	O
+,	O
+000	O
+and	O
+around	O
+100	O
+,	O
+000	O
+migrant	O
+workers	O
+in	O
+Guiyu	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+We	O
+chose	O
+four	O
+villages	O
+for	O
+their	O
+differences	O
+in	O
+the	O
+scale	O
+and	O
+type	O
+of	O
+e	O
+-	O
+waste	O
+processing	O
+.	O
+
+Beilin	O
+village	O
+has	O
+dense	O
+e	O
+-	O
+waste	O
+workshops	O
+mainly	O
+involved	O
+in	O
+equipment	O
+dismantling	O
+,	O
+circuit	O
+board	O
+baking	O
+,	O
+and	O
+acid	O
+baths	O
+;	O
+Dutou	O
+village	O
+specializes	O
+in	O
+plastics	O
+sorting	O
+,	O
+including	O
+manually	O
+stripping	O
+plastic	O
+materials	O
+from	O
+electronic	O
+products	O
+and	O
+then	O
+crudely	O
+classifying	O
+them	O
+;	O
+Huamei	O
+village	O
+had	O
+workshops	O
+similar	O
+to	O
+those	O
+of	O
+Beilin	O
+,	O
+but	O
+they	O
+are	O
+fewer	O
+and	O
+scattered	O
+;	O
+and	O
+Longgang	O
+village	O
+was	O
+involved	O
+in	O
+plastic	O
+reprocessing	O
+in	O
+which	O
+plastics	O
+collected	O
+from	O
+Dutou	O
+and	O
+other	O
+villages	O
+were	O
+washed	O
+and	O
+smashed	O
+into	O
+tiny	O
+pieces	O
+of	O
+recycled	O
+plastic	O
+.	O
+
+We	O
+used	O
+the	O
+neighboring	O
+town	O
+of	O
+Chendian	O
+as	O
+a	O
+control	O
+because	O
+the	O
+local	O
+residents	O
+work	O
+mainly	O
+in	O
+the	O
+textiles	O
+industry	O
+,	O
+not	O
+in	O
+e	O
+-	O
+waste	O
+processing	O
+.	O
+
+The	O
+population	O
+,	O
+traffic	O
+density	O
+,	O
+lifestyle	O
+,	O
+and	O
+socioeconomic	O
+status	O
+were	O
+very	O
+similar	O
+to	O
+those	O
+of	O
+Guiyu	O
+.	O
+
+Study	O
+population	O
+
+The	O
+study	O
+population	O
+was	O
+composed	O
+of	O
+children	B
+<	O
+=	O
+6	O
+years	O
+of	O
+age	O
+.	O
+
+No	O
+children	B
+involved	O
+in	O
+the	O
+study	O
+had	O
+any	O
+occupational	O
+exposure	O
+to	O
+e	O
+-	O
+waste	O
+.	O
+
+A	O
+cluster	O
+sample	O
+of	O
+165	O
+children	B
+with	O
+a	O
+median	O
+age	O
+of	O
+5	O
+.	O
+0	O
+years	O
+lived	O
+in	O
+the	O
+four	O
+villages	O
+of	O
+Guiyu	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Sixty	O
+-	O
+one	O
+children	B
+with	O
+a	O
+median	O
+age	O
+of	O
+4	O
+.	O
+0	O
+years	O
+resided	O
+in	O
+Chendian	O
+were	O
+included	O
+in	O
+the	O
+study	O
+for	O
+comparison	O
+.	O
+
+After	O
+written	O
+informed	O
+consent	O
+was	O
+obtained	O
+from	O
+the	O
+parents	O
+or	O
+guardians	O
+,	O
+blood	O
+samples	O
+were	O
+collected	O
+from	O
+the	O
+children	B
+at	O
+village	O
+kindergartens	O
+.	O
+
+To	O
+facilitate	O
+the	O
+counseling	O
+process	O
+,	O
+advice	O
+on	O
+dietary	O
+and	O
+eating	O
+habits	O
+to	O
+minimize	O
+lead	O
+exposure	O
+were	O
+provided	O
+to	O
+the	O
+local	O
+residents	O
+.	O
+
+All	O
+children	B
+found	O
+to	O
+have	O
+high	O
+BLLs	O
+were	O
+advised	O
+to	O
+get	O
+further	O
+hospital	O
+treatment	O
+.	O
+
+The	O
+study	O
+was	O
+approved	O
+by	O
+the	O
+Human	O
+Ethics	O
+Committee	O
+of	O
+Shantou	O
+University	O
+Medical	O
+College	O
+.	O
+
+Measurement	O
+of	O
+BLLs	O
+and	O
+hemoglobin	O
+
+Venipuncture	O
+blood	O
+samples	O
+were	O
+obtained	O
+from	O
+each	O
+volunteer	O
+at	O
+the	O
+kindergarten	O
+,	O
+and	O
+collected	O
+in	O
+lead	O
+-	O
+free	O
+tubes	O
+by	O
+trained	O
+nurses	O
+.	O
+
+Lead	O
+in	O
+total	O
+blood	O
+was	O
+analyzed	O
+by	O
+graphite	O
+furnace	O
+atomic	O
+absorption	O
+spectrometry	O
+(	O
+GFAAS	O
+)	O
+,	O
+which	O
+consisted	O
+of	O
+a	O
+Shimadzu	O
+AA	O
+-	O
+660	O
+AAS	O
+and	O
+GFA	O
+-	O
+4B	O
+graphite	O
+furnace	O
+atomizer	O
+and	O
+an	O
+ACS	O
+-	O
+60G	O
+autosampler	O
+(	O
+Shimadzu	O
+Corporation	O
+,	O
+Kyoto	O
+,	O
+Japan	O
+)	O
+.	O
+
+The	O
+main	O
+parameters	O
+used	O
+for	O
+the	O
+determination	O
+were	O
+a	O
+wavelength	O
+of	O
+283	O
+.	O
+3	O
+nm	O
+,	O
+current	O
+of	O
+8	O
+mA	O
+,	O
+a	O
+slit	O
+width	O
+of	O
+1	O
+.	O
+00	O
+nm	O
+,	O
+drying	O
+at	O
+150	O
+degrees	O
+C	O
+,	O
+ashing	O
+at	O
+325	O
+degrees	O
+C	O
+,	O
+and	O
+atomization	O
+at	O
+1	O
+,	O
+400	O
+degrees	O
+C	O
+.	O
+
+The	O
+accuracy	O
+of	O
+the	O
+method	O
+was	O
+controlled	O
+by	O
+recoveries	O
+between	O
+95	O
+%	O
+and	O
+107	O
+%	O
+from	O
+the	O
+spiked	O
+blood	O
+samples	O
+.	O
+
+Repeated	O
+analyses	O
+of	O
+standard	O
+solutions	O
+confirmed	O
+the	O
+method	O
+'	O
+s	O
+precision	O
+.	O
+
+The	O
+BLLs	O
+were	O
+expressed	O
+in	O
+micrograms	O
+per	O
+deciliter	O
+(	O
+1	O
+mu	O
+g	O
+/	O
+dL	O
+=	O
+0	O
+.	O
+0484	O
+mu	O
+mol	O
+/	O
+L	O
+)	O
+.	O
+
+Meanwhile	O
+,	O
+we	O
+assessed	O
+hemoglobin	O
+(	O
+Hgb	O
+)	O
+levels	O
+by	O
+hemoglobin	O
+cyanide	O
+method	O
+with	O
+hemoglobinometer	O
+(	O
+XK	O
+-	O
+2	O
+,	O
+JiangSu	O
+,	O
+China	O
+)	O
+.	O
+
+Evaluation	O
+of	O
+physical	O
+developmental	O
+indexes	O
+
+Children	B
+'	O
+s	O
+physical	O
+growth	O
+and	O
+development	O
+,	O
+such	O
+as	O
+body	O
+height	O
+,	O
+weight	O
+,	O
+and	O
+head	O
+and	O
+chest	O
+circumferences	O
+were	O
+measured	O
+when	O
+blood	O
+samples	O
+were	O
+collected	O
+.	O
+
+Weight	O
+and	O
+height	O
+were	O
+measured	O
+using	O
+a	O
+weighing	O
+and	O
+height	O
+scale	O
+(	O
+TZ120	O
+;	O
+Yuyao	O
+Balance	O
+Instrument	O
+Factory	O
+,	O
+Yuyao	O
+,	O
+China	O
+)	O
+with	O
+maximum	O
+weight	O
+of	O
+120	O
+kg	O
+(	O
+minimum	O
+scale	O
+,	O
+50	O
+g	O
+)	O
+and	O
+minimum	O
+height	O
+of	O
+70	O
+cm	O
+(	O
+minimum	O
+scale	O
+,	O
+0	O
+.	O
+5	O
+cm	O
+)	O
+.	O
+
+Head	O
+and	O
+chest	O
+circumferences	O
+were	O
+measured	O
+using	O
+graduated	O
+anthropometric	O
+tapes	O
+.	O
+
+Statistical	O
+analyses	O
+
+We	O
+performed	O
+statistical	O
+analyses	O
+using	O
+SPSS	O
+version	O
+10	O
+.	O
+0	O
+software	O
+(	O
+SPSS	O
+,	O
+Chicago	O
+,	O
+IL	O
+,	O
+USA	O
+)	O
+.	O
+
+We	O
+used	O
+independent	O
+sample	O
+t	O
+-	O
+tests	O
+or	O
+covariance	O
+analyses	O
+for	O
+comparisons	O
+of	O
+mean	O
+,	O
+chi	O
+-	O
+square	O
+analyses	O
+for	O
+test	O
+of	O
+frequency	O
+data	O
+,	O
+and	O
+linear	O
+regression	O
+analysis	O
+for	O
+the	O
+association	O
+between	O
+BLLs	O
+and	O
+age	O
+.	O
+
+Differences	O
+were	O
+considered	O
+significant	O
+with	O
+a	O
+p	O
+-	O
+value	O
+<	O
+0	O
+.	O
+05	O
+.	O
+
+Results	O
+
+Observation	O
+of	O
+e	O
+-	O
+waste	O
+processing	O
+
+The	O
+primitive	O
+e	O
+-	O
+waste	O
+recycling	O
+procedures	O
+in	O
+Guiyu	O
+were	O
+mainly	O
+as	O
+follows	O
+:	O
+a	O
+)	O
+Old	O
+electronic	O
+equipment	O
+was	O
+dismantled	O
+(	O
+Figure	O
+2	O
+)	O
+with	O
+electric	O
+drill	O
+,	O
+cutter	O
+,	O
+hammer	O
+,	O
+and	O
+screwdriver	O
+into	O
+component	O
+parts	O
+such	O
+as	O
+monitor	O
+,	O
+hard	O
+drive	O
+,	O
+CD	O
+driver	O
+,	O
+wires	O
+,	O
+cables	O
+,	O
+circuit	O
+boards	O
+,	O
+transformer	O
+,	O
+charger	O
+,	O
+battery	O
+,	O
+and	O
+plastic	O
+or	O
+metal	O
+frame	O
+that	O
+are	O
+sold	O
+for	O
+reuse	O
+or	O
+to	O
+other	O
+workshops	O
+for	O
+further	O
+recycling	O
+.	O
+
+b	O
+)	O
+Circuit	O
+boards	O
+(	O
+Figure	O
+3	O
+)	O
+of	O
+computers	O
+and	O
+other	O
+large	O
+appliances	O
+were	O
+heated	O
+over	O
+coal	O
+fires	O
+to	O
+melt	O
+the	O
+solder	O
+to	O
+release	O
+valuable	O
+electronic	O
+components	O
+,	O
+such	O
+as	O
+diodes	O
+,	O
+resistors	O
+,	O
+and	O
+microchips	O
+.	O
+
+c	O
+)	O
+Circuit	O
+boards	O
+of	O
+cell	O
+phones	O
+and	O
+other	O
+hand	O
+-	O
+held	O
+devices	O
+were	O
+taken	O
+apart	O
+by	O
+a	O
+electrothermal	O
+machine	O
+(	O
+Figure	O
+4	O
+)	O
+,	O
+which	O
+was	O
+a	O
+particular	O
+environmental	O
+and	O
+human	B
+health	O
+concern	O
+in	O
+the	O
+processing	O
+of	O
+e	O
+-	O
+waste	O
+in	O
+Guiyu	O
+.	O
+
+d	O
+)	O
+In	O
+acid	O
+baths	O
+(	O
+Figure	O
+5	O
+)	O
+,	O
+some	O
+microchips	O
+and	O
+computer	O
+parts	O
+were	O
+soaked	O
+to	O
+extract	O
+precious	O
+gold	O
+and	O
+palladium	O
+,	O
+from	O
+which	O
+the	O
+waste	O
+acids	O
+were	O
+discharged	O
+into	O
+nearby	O
+fields	O
+and	O
+streams	O
+.	O
+
+e	O
+)	O
+Wires	O
+and	O
+cables	O
+were	O
+stripped	O
+or	O
+simply	O
+burnt	O
+in	O
+open	O
+air	O
+to	O
+recover	O
+metals	O
+.	O
+
+f	O
+)	O
+Printer	O
+cartridges	O
+were	O
+ripped	O
+apart	O
+for	O
+their	O
+toner	O
+and	O
+recyclable	O
+aluminum	O
+,	O
+steel	O
+,	O
+and	O
+plastic	O
+parts	O
+.	O
+
+g	O
+)	O
+Plastic	O
+[	O
+e	O
+.	O
+g	O
+.	O
+,	O
+polyvinyl	O
+chloride	O
+(	O
+PVC	O
+)	O
+,	O
+acrylonitrile	O
+butadiene	O
+styrene	O
+copolymer	O
+(	O
+ABS	O
+)	O
+,	O
+high	O
+-	O
+density	O
+polyethylene	O
+(	O
+HDPE	O
+)	O
+]	O
+was	O
+sorted	O
+by	O
+workers	O
+according	O
+to	O
+rigidity	O
+,	O
+color	O
+,	O
+and	O
+luster	O
+.	O
+
+Plastic	O
+scraps	O
+that	O
+cannot	O
+be	O
+sorted	O
+visually	O
+must	O
+be	O
+burned	O
+and	O
+classified	O
+by	O
+burning	O
+odor	O
+.	O
+
+Another	O
+way	O
+to	O
+sort	O
+different	O
+plastics	O
+was	O
+gravitational	O
+separation	O
+into	O
+ceramic	O
+jugs	O
+with	O
+brine	O
+(	O
+Figure	O
+6	O
+)	O
+,	O
+after	O
+which	O
+the	O
+pieces	O
+were	O
+spread	O
+on	O
+the	O
+sidewalk	O
+to	O
+dry	O
+;	O
+h	O
+)	O
+For	O
+reprocessing	O
+,	O
+after	O
+sorting	O
+plastic	O
+scraps	O
+were	O
+fed	O
+into	O
+grinders	O
+that	O
+spit	O
+out	O
+tiny	O
+pieces	O
+of	O
+plastic	O
+.	O
+
+i	O
+)	O
+For	O
+metals	O
+sorting	O
+and	O
+reprocessing	O
+,	O
+transformers	O
+,	O
+chargers	O
+,	O
+batteries	O
+,	O
+and	O
+cathode	O
+-	O
+ray	O
+tubes	O
+were	O
+separated	O
+and	O
+hammered	O
+open	O
+for	O
+recycling	O
+metals	O
+such	O
+as	O
+copper	O
+,	O
+steel	O
+,	O
+silver	O
+,	O
+aluminum	O
+,	O
+which	O
+were	O
+then	O
+reprocessed	O
+to	O
+raw	O
+material	O
+.	O
+
+Although	O
+the	O
+methods	O
+for	O
+processing	O
+e	O
+-	O
+waste	O
+were	O
+primitive	O
+,	O
+the	O
+coordination	O
+of	O
+e	O
+-	O
+waste	O
+recycling	O
+in	O
+Guiyu	O
+was	O
+very	O
+well	O
+organized	O
+into	O
+specific	O
+tasks	O
+.	O
+
+Workshops	O
+specializing	O
+in	O
+dismantled	O
+equipment	O
+would	O
+not	O
+conduct	O
+circuit	O
+board	O
+baking	O
+or	O
+plastics	O
+and	O
+metals	O
+reprocessing	O
+.	O
+
+The	O
+chain	O
+of	O
+recycling	O
+components	O
+from	O
+each	O
+type	O
+of	O
+e	O
+-	O
+waste	O
+was	O
+well	O
+established	O
+in	O
+the	O
+town	O
+.	O
+
+BLLs	O
+in	O
+children	B
+
+We	O
+collected	O
+blood	O
+from	O
+165	O
+children	B
+in	O
+Guiyu	O
+and	O
+61	O
+children	B
+in	O
+Chendian	O
+and	O
+measured	O
+the	O
+BLLs	O
+in	O
+these	O
+children	B
+.	O
+
+Table	O
+1	O
+shows	O
+that	O
+the	O
+BLLs	O
+corresponded	O
+to	O
+the	O
+children	B
+'	O
+s	O
+age	O
+,	O
+sex	O
+,	O
+and	O
+town	O
+of	O
+residence	O
+.	O
+
+As	O
+expected	O
+,	O
+BLLs	O
+among	O
+Guiyu	O
+children	B
+were	O
+much	O
+higher	O
+than	O
+those	O
+in	O
+the	O
+children	B
+of	O
+Chendian	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Among	O
+Guiyu	O
+children	B
+,	O
+135	O
+(	O
+81	O
+.	O
+8	O
+%	O
+)	O
+had	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+whereas	O
+23	O
+(	O
+37	O
+.	O
+7	O
+%	O
+)	O
+in	O
+Chendian	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+had	O
+high	O
+levels	O
+.	O
+
+Among	O
+135	O
+(	O
+81	O
+.	O
+8	O
+%	O
+)	O
+Guiyu	O
+children	B
+with	O
+elevated	O
+BLLs	O
+,	O
+61	O
+.	O
+8	O
+%	O
+and	O
+20	O
+%	O
+had	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+and	O
+20	O
+mu	O
+g	O
+/	O
+dL	O
+respectively	O
+,	O
+but	O
+lead	O
+levels	O
+>	O
+45	O
+mu	O
+g	O
+/	O
+dL	O
+were	O
+not	O
+found	O
+.	O
+
+And	O
+BLLs	O
+of	O
+Guiyu	O
+increased	O
+somewhat	O
+with	O
+age	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+;	O
+older	O
+children	B
+tended	O
+to	O
+have	O
+higher	O
+BLLs	O
+than	O
+younger	O
+ones	O
+.	O
+
+We	O
+found	O
+no	O
+evidence	O
+for	O
+the	O
+association	O
+in	O
+lead	O
+concentrations	O
+or	O
+prevalence	O
+of	O
+elevated	O
+BLLs	O
+differentiated	O
+by	O
+sex	O
+(	O
+both	O
+p	O
+>	O
+0	O
+.	O
+05	O
+)	O
+.	O
+
+Table	O
+2	O
+presents	O
+BLLs	O
+for	O
+165	O
+exposed	O
+children	B
+in	O
+the	O
+four	O
+villages	O
+.	O
+
+The	O
+findings	O
+showed	O
+that	O
+BLLs	O
+from	O
+different	O
+villages	O
+were	O
+in	O
+the	O
+following	O
+descending	O
+order	O
+:	O
+Beilin	O
+,	O
+19	O
+.	O
+34	O
+mu	O
+g	O
+/	O
+dL	O
+>	O
+Dutou	O
+,	O
+17	O
+.	O
+86	O
+mu	O
+g	O
+/	O
+dL	O
+>	O
+Huamei	O
+,	O
+14	O
+.	O
+23	O
+mu	O
+g	O
+/	O
+dL	O
+>	O
+Longgang	O
+,	O
+13	O
+.	O
+13	O
+mu	O
+g	O
+/	O
+dL	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Children	B
+living	O
+in	O
+Beilin	O
+,	O
+where	O
+the	O
+number	O
+of	O
+e	O
+-	O
+waste	O
+workshops	O
+specializing	O
+in	O
+equipment	O
+dismantling	O
+,	O
+circuit	O
+board	O
+baking	O
+,	O
+and	O
+acid	O
+baths	O
+,	O
+had	O
+the	O
+highest	O
+BLLs	O
+.	O
+
+Dutou	O
+,	O
+which	O
+had	O
+many	O
+workshops	O
+specializing	O
+in	O
+plastics	O
+sorting	O
+,	O
+including	O
+strip	O
+plastic	O
+materials	O
+from	O
+e	O
+-	O
+waste	O
+,	O
+had	O
+the	O
+second	O
+highest	O
+BLLs	O
+in	O
+children	B
+.	O
+
+Huamei	O
+had	O
+e	O
+-	O
+waste	O
+workshops	O
+similar	O
+to	O
+those	O
+of	O
+Beilin	O
+,	O
+but	O
+fewer	O
+and	O
+less	O
+centralized	O
+;	O
+the	O
+BLLs	O
+of	O
+Huamei	O
+children	B
+were	O
+much	O
+lower	O
+than	O
+those	O
+of	O
+Beilin	O
+and	O
+Dutou	O
+.	O
+
+Longgang	O
+,	O
+a	O
+village	O
+specializing	O
+in	O
+reprocessing	O
+plastics	O
+collected	O
+from	O
+other	O
+villages	O
+that	O
+had	O
+no	O
+workshops	O
+directly	O
+processing	O
+e	O
+-	O
+waste	O
+,	O
+had	O
+the	O
+lowest	O
+BLLs	O
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+difference	O
+in	O
+BLLs	O
+among	O
+the	O
+children	B
+of	O
+the	O
+four	O
+villages	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+In	O
+Beilin	O
+and	O
+Dutou	O
+,	O
+88	O
+.	O
+8	O
+%	O
+and	O
+100	O
+%	O
+children	B
+had	O
+elevated	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+respectively	O
+.	O
+
+As	O
+far	O
+as	O
+physical	O
+indexes	O
+and	O
+Hgb	O
+levels	O
+were	O
+concerned	O
+,	O
+there	O
+was	O
+no	O
+significant	O
+difference	O
+between	O
+Guiyu	O
+and	O
+Chendian	O
+(	O
+p	O
+>	O
+0	O
+.	O
+05	O
+,	O
+Table	O
+3	O
+)	O
+.	O
+
+Discussion	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+observed	O
+that	O
+the	O
+processing	O
+of	O
+e	O
+-	O
+waste	O
+in	O
+Guiyu	O
+was	O
+very	O
+primitive	O
+and	O
+the	O
+recycling	O
+industry	O
+depended	O
+mainly	O
+on	O
+manual	O
+processing	O
+methods	O
+.	O
+
+Despite	O
+the	O
+fact	O
+that	O
+the	O
+coordination	O
+of	O
+the	O
+e	O
+-	O
+waste	O
+recycling	O
+is	O
+well	O
+organized	O
+in	O
+family	O
+-	O
+based	O
+small	O
+business	O
+units	O
+,	O
+the	O
+manual	O
+processing	O
+methods	O
+and	O
+the	O
+deposition	O
+of	O
+the	O
+e	O
+-	O
+waste	O
+have	O
+contributed	O
+to	O
+the	O
+contamination	O
+by	O
+heavy	O
+metals	O
+in	O
+the	O
+living	O
+environment	O
+.	O
+
+Examination	O
+of	O
+the	O
+possible	O
+impact	O
+of	O
+the	O
+e	O
+-	O
+waste	O
+industry	O
+on	O
+the	O
+BLLs	O
+of	O
+children	B
+living	O
+in	O
+Guiyu	O
+revealed	O
+that	O
+Guiyu	O
+children	B
+had	O
+significantly	O
+higher	O
+BLLs	O
+than	O
+Chendian	O
+children	B
+.	O
+
+Of	O
+children	B
+tested	O
+in	O
+Guiyu	O
+,	O
+81	O
+.	O
+8	O
+%	O
+had	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+indicating	O
+a	O
+correlation	O
+between	O
+the	O
+BLLs	O
+in	O
+children	B
+and	O
+the	O
+numbers	O
+of	O
+e	O
+-	O
+waste	O
+workshops	O
+.	O
+
+We	O
+speculated	O
+that	O
+the	O
+elevated	O
+BLLs	O
+in	O
+Guiyu	O
+children	B
+may	O
+be	O
+directly	O
+caused	O
+by	O
+the	O
+contamination	O
+of	O
+the	O
+lead	O
+during	O
+e	O
+-	O
+waste	O
+recycling	O
+.	O
+
+However	O
+,	O
+further	O
+study	O
+should	O
+be	O
+conducted	O
+to	O
+determine	O
+the	O
+relationship	O
+between	O
+BLLs	O
+in	O
+Children	B
+and	O
+the	O
+actual	O
+lead	O
+contamination	O
+in	O
+the	O
+environment	O
+.	O
+
+Lead	O
+is	O
+considered	O
+one	O
+of	O
+the	O
+major	O
+heavy	O
+metal	O
+contaminants	O
+during	O
+the	O
+process	O
+of	O
+e	O
+-	O
+waste	O
+recycling	O
+.	O
+
+A	O
+cathode	O
+ray	O
+tube	O
+inside	O
+a	O
+television	O
+set	O
+or	O
+a	O
+computer	O
+monitor	O
+contains	O
+an	O
+average	O
+of	O
+4	O
+-	O
+8	O
+lb	O
+lead	O
+;	O
+monitor	O
+glass	O
+contains	O
+about	O
+20	O
+%	O
+lead	O
+by	O
+weight	O
+;	O
+a	O
+typical	O
+battery	O
+weighs	O
+36	O
+lb	O
+and	O
+contains	O
+about	O
+18	O
+lb	O
+of	O
+lead	O
+.	O
+
+For	O
+decades	O
+,	O
+lead	O
+as	O
+a	O
+major	O
+component	O
+of	O
+solders	O
+has	O
+been	O
+used	O
+to	O
+attach	O
+electronic	O
+components	O
+to	O
+printed	O
+circuit	O
+boards	O
+.	O
+
+Lead	O
+compounds	O
+have	O
+also	O
+been	O
+used	O
+as	O
+stabilizers	O
+in	O
+some	O
+PVC	O
+cables	O
+and	O
+other	O
+products	O
+.	O
+
+Our	O
+study	O
+demonstrated	O
+in	O
+Guiyu	O
+a	O
+significant	O
+increasing	O
+trend	O
+in	O
+BLLs	O
+with	O
+increasing	O
+age	O
+;	O
+older	O
+children	B
+tended	O
+to	O
+have	O
+higher	O
+BLLs	O
+than	O
+younger	O
+ones	O
+.	O
+
+This	O
+might	O
+be	O
+the	O
+result	O
+of	O
+increasing	O
+exposure	O
+risk	O
+because	O
+older	O
+children	B
+might	O
+have	O
+more	O
+outdoor	O
+activities	O
+.	O
+
+In	O
+addition	O
+,	O
+it	O
+may	O
+also	O
+be	O
+attributed	O
+to	O
+the	O
+fact	O
+that	O
+the	O
+heaviest	O
+lead	O
+-	O
+contaminated	O
+zone	O
+in	O
+air	O
+after	O
+the	O
+burning	O
+of	O
+the	O
+e	O
+-	O
+waste	O
+was	O
+75	O
+-	O
+100	O
+cm	O
+above	O
+the	O
+ground	O
+(	O
+Wang	O
+and	O
+Zhang	O
+2006	O
+)	O
+,	O
+which	O
+was	O
+the	O
+height	O
+range	O
+for	O
+normal	O
+Chinese	O
+children	B
+5	O
+-	O
+6	O
+years	O
+of	O
+age	O
+.	O
+
+In	O
+China	O
+,	O
+the	O
+mean	O
+BLL	O
+of	O
+children	B
+was	O
+9	O
+.	O
+29	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+and	O
+33	O
+.	O
+8	O
+%	O
+of	O
+the	O
+subjects	O
+had	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+;	O
+boys	B
+'	O
+mean	O
+BLL	O
+was	O
+9	O
+.	O
+64	O
+mu	O
+g	O
+/	O
+dL	O
+,	O
+significantly	O
+higher	O
+than	O
+the	O
+girls	B
+'	O
+mean	O
+BLL	O
+of	O
+8	O
+.	O
+94	O
+mu	O
+g	O
+/	O
+dL	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+(	O
+Wang	O
+and	O
+Zhang	O
+2006	O
+)	O
+.	O
+
+Generally	O
+in	O
+China	O
+,	O
+BLLs	O
+of	O
+children	B
+living	O
+in	O
+industrial	O
+and	O
+urban	O
+areas	O
+were	O
+significantly	O
+higher	O
+than	O
+those	O
+of	O
+children	B
+in	O
+suburbs	O
+and	O
+rural	O
+areas	O
+(	O
+Wang	O
+and	O
+Zhang	O
+2006	O
+)	O
+.	O
+
+In	O
+Guiyu	O
+,	O
+the	O
+BLLs	O
+of	O
+children	B
+were	O
+higher	O
+than	O
+the	O
+mean	O
+level	O
+in	O
+China	O
+,	O
+and	O
+there	O
+were	O
+no	O
+significant	O
+different	O
+between	O
+boys	B
+and	O
+girls	B
+.	O
+
+Although	O
+Guiyu	O
+is	O
+rural	O
+,	O
+the	O
+children	B
+'	O
+s	O
+BLLs	O
+were	O
+nearly	O
+double	O
+those	O
+of	O
+a	O
+nearby	O
+urban	O
+area	O
+,	O
+Shantou	O
+City	O
+(	O
+7	O
+.	O
+9	O
+mu	O
+g	O
+/	O
+dL	O
+;	O
+Luo	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Compared	O
+with	O
+results	O
+from	O
+studies	O
+conducted	O
+in	O
+some	O
+other	O
+part	O
+of	O
+Guangdong	O
+province	O
+,	O
+such	O
+as	O
+Zhongshan	O
+City	O
+(	O
+7	O
+.	O
+45	O
+mu	O
+g	O
+/	O
+dL	O
+;	O
+Huang	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+and	O
+Shenzhen	O
+City	O
+(	O
+9	O
+.	O
+06	O
+mu	O
+g	O
+/	O
+dL	O
+;	O
+Wang	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+,	O
+we	O
+observed	O
+higher	O
+BLLs	O
+not	O
+only	O
+in	O
+Guiyu	O
+children	B
+,	O
+but	O
+also	O
+in	O
+Chendian	O
+children	B
+(	O
+9	O
+.	O
+94	O
+mu	O
+g	O
+/	O
+dL	O
+)	O
+.	O
+
+The	O
+lead	O
+contamination	O
+may	O
+have	O
+spread	O
+from	O
+Guiyu	O
+to	O
+nearby	O
+Chendian	O
+by	O
+dust	O
+,	O
+river	O
+,	O
+and	O
+air	O
+and	O
+contributed	O
+to	O
+the	O
+elevation	O
+of	O
+Chendian	O
+children	B
+'	O
+s	O
+BLLs	O
+.	O
+
+In	O
+conclusion	O
+,	O
+elevated	O
+BLLs	O
+in	O
+Guiyu	O
+children	B
+are	O
+common	O
+as	O
+a	O
+result	O
+of	O
+exposure	O
+to	O
+lead	O
+contamination	O
+caused	O
+by	O
+primitive	O
+e	O
+-	O
+waste	O
+recycling	O
+activities	O
+.	O
+
+Lead	O
+contamination	O
+from	O
+e	O
+-	O
+waste	O
+processing	O
+appears	O
+to	O
+have	O
+reached	O
+the	O
+level	O
+considered	O
+to	O
+be	O
+a	O
+serious	O
+threat	O
+to	O
+children	B
+'	O
+s	O
+health	O
+around	O
+the	O
+e	O
+-	O
+waste	O
+recycling	O
+area	O
+.	O
+
+Based	O
+on	O
+these	O
+threats	O
+,	O
+it	O
+is	O
+necessary	O
+to	O
+increase	O
+public	O
+awareness	O
+about	O
+the	O
+effects	O
+of	O
+exposure	O
+to	O
+lead	O
+from	O
+e	O
+-	O
+waste	O
+and	O
+arouse	O
+local	O
+governments	O
+'	O
+interest	O
+in	O
+public	O
+health	O
+and	O
+safety	O
+,	O
+so	O
+that	O
+an	O
+infrastructure	O
+for	O
+safe	O
+management	O
+of	O
+e	O
+-	O
+waste	O
+can	O
+be	O
+established	O
+.	O
+
+More	O
+important	O
+,	O
+responsible	O
+management	O
+strategies	O
+should	O
+be	O
+undertaken	O
+to	O
+minimize	O
+e	O
+-	O
+waste	O
+production	O
+and	O
+make	O
+e	O
+-	O
+waste	O
+components	O
+more	O
+easily	O
+recycled	O
+and	O
+reused	O
+.	O
+
+Correction	O
+
+In	O
+the	O
+Abstract	O
+and	O
+Discussion	O
+,	O
+the	O
+percentage	O
+of	O
+Guiyu	O
+children	B
+with	O
+BLLs	O
+>	O
+10	O
+mu	O
+g	O
+/	O
+dL	O
+has	O
+been	O
+corrected	O
+from	O
+88	O
+%	O
+in	O
+the	O
+original	O
+manuscript	O
+published	O
+online	O
+to	O
+81	O
+.	O
+8	O
+%	O
+.	O
+
+Dynein	O
+Modifiers	O
+in	O
+C	B
+.	I
+elegans	I
+:	O
+Light	O
+Chains	O
+Suppress	O
+Conditional	O
+Heavy	O
+Chain	O
+Mutants	O
+
+Abstract	O
+
+Cytoplasmic	O
+dynein	O
+is	O
+a	O
+microtubule	O
+-	O
+dependent	O
+motor	O
+protein	O
+that	O
+functions	O
+in	O
+mitotic	O
+cells	O
+during	O
+centrosome	O
+separation	O
+,	O
+metaphase	O
+chromosome	O
+congression	O
+,	O
+anaphase	O
+spindle	O
+elongation	O
+,	O
+and	O
+chromosome	O
+segregation	O
+.	O
+
+Dynein	O
+is	O
+also	O
+utilized	O
+during	O
+interphase	O
+for	O
+vesicle	O
+transport	O
+and	O
+organelle	O
+positioning	O
+.	O
+
+While	O
+numerous	O
+cellular	O
+processes	O
+require	O
+cytoplasmic	O
+dynein	O
+,	O
+the	O
+mechanisms	O
+that	O
+target	O
+and	O
+regulate	O
+this	O
+microtubule	O
+motor	O
+remain	O
+largely	O
+unknown	O
+.	O
+
+By	O
+screening	O
+a	O
+conditional	O
+Caenorhabditis	B
+elegans	I
+cytoplasmic	O
+dynein	O
+heavy	O
+chain	O
+mutant	O
+at	O
+a	O
+semipermissive	O
+temperature	O
+with	O
+a	O
+genome	O
+-	O
+wide	O
+RNA	O
+interference	O
+library	O
+to	O
+reduce	O
+gene	O
+functions	O
+,	O
+we	O
+have	O
+isolated	O
+and	O
+characterized	O
+twenty	O
+dynein	O
+-	O
+specific	O
+suppressor	O
+genes	O
+.	O
+
+When	O
+reduced	O
+in	O
+function	O
+,	O
+these	O
+genes	O
+suppress	O
+dynein	O
+mutants	O
+but	O
+not	O
+other	O
+conditionally	O
+mutant	O
+loci	O
+,	O
+and	O
+twelve	O
+of	O
+the	O
+20	O
+specific	O
+suppressors	O
+do	O
+not	O
+exhibit	O
+sterile	O
+or	O
+lethal	O
+phenotypes	O
+when	O
+their	O
+function	O
+is	O
+reduced	O
+in	O
+wild	O
+-	O
+type	O
+worms	B
+.	O
+
+Many	O
+of	O
+the	O
+suppressor	O
+proteins	O
+,	O
+including	O
+two	O
+dynein	O
+light	O
+chains	O
+,	O
+localize	O
+to	O
+subcellular	O
+sites	O
+that	O
+overlap	O
+with	O
+those	O
+reported	O
+by	O
+others	O
+for	O
+the	O
+dynein	O
+heavy	O
+chain	O
+.	O
+
+Furthermore	O
+,	O
+knocking	O
+down	O
+any	O
+one	O
+of	O
+four	O
+putative	O
+dynein	O
+accessory	O
+chains	O
+suppresses	O
+the	O
+conditional	O
+heavy	O
+chain	O
+mutants	O
+,	O
+suggesting	O
+that	O
+some	O
+accessory	O
+chains	O
+negatively	O
+regulate	O
+heavy	O
+chain	O
+function	O
+.	O
+
+We	O
+also	O
+identified	O
+29	O
+additional	O
+genes	O
+that	O
+,	O
+when	O
+reduced	O
+in	O
+function	O
+,	O
+suppress	O
+conditional	O
+mutations	O
+not	O
+only	O
+in	O
+dynein	O
+but	O
+also	O
+in	O
+loci	O
+required	O
+for	O
+unrelated	O
+essential	O
+processes	O
+.	O
+
+In	O
+conclusion	O
+,	O
+we	O
+have	O
+identified	O
+twenty	O
+genes	O
+that	O
+in	O
+many	O
+cases	O
+are	O
+not	O
+essential	O
+themselves	O
+but	O
+are	O
+conserved	O
+and	O
+when	O
+reduced	O
+in	O
+function	O
+can	O
+suppress	O
+conditionally	O
+lethal	O
+C	B
+.	I
+elegans	I
+cytoplasmic	O
+dynein	O
+heavy	O
+chain	O
+mutants	O
+.	O
+
+We	O
+conclude	O
+that	O
+conserved	O
+but	O
+nonessential	O
+genes	O
+contribute	O
+to	O
+dynein	O
+function	O
+during	O
+the	O
+essential	O
+process	O
+of	O
+mitosis	O
+.	O
+
+Microtubules	O
+and	O
+microtubule	O
+-	O
+dependent	O
+motor	O
+proteins	O
+segregate	O
+chromosomes	O
+during	O
+mitosis	O
+and	O
+also	O
+promote	O
+cellular	O
+organization	O
+in	O
+nondividing	O
+cells	O
+.	O
+
+An	O
+essential	O
+motor	O
+protein	O
+complex	O
+called	O
+cytoplasmic	O
+dynein	O
+powers	O
+many	O
+aspects	O
+of	O
+microtubule	O
+-	O
+dependent	O
+transport	O
+,	O
+but	O
+it	O
+is	O
+currently	O
+unclear	O
+how	O
+dynein	O
+is	O
+regulated	O
+such	O
+that	O
+it	O
+can	O
+execute	O
+different	O
+processes	O
+.	O
+
+We	O
+have	O
+performed	O
+a	O
+genome	O
+-	O
+wide	O
+screen	O
+to	O
+isolate	O
+genes	O
+that	O
+are	O
+involved	O
+in	O
+dynein	O
+-	O
+dependent	O
+processes	O
+.	O
+
+We	O
+determined	O
+that	O
+20	O
+of	O
+the	O
+49	O
+genes	O
+we	O
+identified	O
+specifically	O
+influenced	O
+the	O
+viability	O
+of	O
+dynein	O
+mutant	O
+strains	O
+but	O
+not	O
+the	O
+viability	O
+of	O
+other	O
+C	B
+.	I
+elegans	I
+mutants	O
+.	O
+
+Many	O
+of	O
+the	O
+proteins	O
+that	O
+specifically	O
+influence	O
+dynein	O
+localized	O
+to	O
+subcellular	O
+sites	O
+where	O
+the	O
+dynein	O
+heavy	O
+chain	O
+has	O
+been	O
+reported	O
+by	O
+others	O
+to	O
+be	O
+found	O
+.	O
+
+Additionally	O
+,	O
+we	O
+identified	O
+four	O
+dynein	O
+components	O
+that	O
+appear	O
+to	O
+negatively	O
+regulate	O
+the	O
+force	O
+-	O
+generating	O
+dynein	O
+heavy	O
+chain	O
+.	O
+
+The	O
+identification	O
+and	O
+initial	O
+characterization	O
+of	O
+this	O
+group	O
+of	O
+genes	O
+represents	O
+a	O
+route	O
+to	O
+identify	O
+genes	O
+that	O
+are	O
+not	O
+themselves	O
+essential	O
+but	O
+do	O
+participate	O
+in	O
+essential	O
+processes	O
+.	O
+
+Introduction	O
+
+The	O
+microtubule	O
+motor	O
+called	O
+cytoplasmic	O
+dynein	O
+has	O
+roles	O
+in	O
+diverse	O
+cellular	O
+processes	O
+including	O
+meiotic	O
+and	O
+mitotic	O
+spindle	O
+assembly	O
+and	O
+function	O
+,	O
+neuronal	O
+transport	O
+,	O
+and	O
+organelle	O
+positioning	O
+[	O
+1	O
+]	O
+.	O
+
+Cytoplasmic	O
+dynein	O
+is	O
+composed	O
+of	O
+a	O
+dimer	O
+of	O
+heavy	O
+chains	O
+(	O
+HCs	O
+)	O
+,	O
+along	O
+with	O
+several	O
+accessory	O
+chains	O
+(	O
+ACs	O
+:	O
+intermediate	O
+,	O
+light	O
+intermediate	O
+,	O
+and	O
+light	O
+chains	O
+)	O
+.	O
+
+Other	O
+dynein	O
+-	O
+interacting	O
+proteins	O
+,	O
+such	O
+as	O
+dynactin	O
+and	O
+LIS1	O
+,	O
+are	O
+likely	O
+present	O
+at	O
+substoichiometric	O
+levels	O
+and	O
+further	O
+modulate	O
+dynein	O
+function	O
+.	O
+
+The	O
+HCs	O
+contain	O
+both	O
+ATPase	O
+and	O
+microtubule	O
+binding	O
+activities	O
+and	O
+are	O
+sufficient	O
+for	O
+microtubule	O
+-	O
+based	O
+motility	O
+in	O
+vitro	O
+,	O
+moving	O
+toward	O
+the	O
+minus	O
+,	O
+or	O
+slow	O
+-	O
+growing	O
+,	O
+end	O
+of	O
+microtubules	O
+[	O
+2	O
+]	O
+.	O
+
+The	O
+dynein	O
+ACs	O
+provide	O
+cargo	O
+docking	O
+sites	O
+and	O
+often	O
+are	O
+encoded	O
+by	O
+multigene	O
+families	O
+in	O
+any	O
+one	O
+species	O
+[	O
+reviewed	O
+in	O
+1	O
+,	O
+3	O
+]	O
+.	O
+
+In	O
+C	B
+.	I
+elegans	I
+,	O
+a	O
+single	O
+gene	O
+called	O
+dhc	O
+-	O
+1	O
+encodes	O
+a	O
+cytoplasmic	O
+dynein	O
+1	O
+HC	O
+,	O
+while	O
+11	O
+other	O
+genes	O
+encode	O
+five	O
+classes	O
+of	O
+predicted	O
+dynein	O
+ACs	O
+[	O
+3	O
+,	O
+4	O
+]	O
+.	O
+
+The	O
+early	O
+C	B
+.	I
+elegans	I
+embryo	O
+is	O
+an	O
+excellent	O
+system	O
+for	O
+investigating	O
+gene	O
+contributions	O
+for	O
+essential	O
+cellular	O
+processes	O
+,	O
+including	O
+cytoskeletal	O
+functions	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+C	B
+.	I
+elegans	I
+dynein	O
+HC	O
+DHC	O
+-	O
+1	O
+is	O
+essential	O
+and	O
+required	O
+for	O
+multiple	O
+microtubule	O
+-	O
+dependent	O
+events	O
+during	O
+early	O
+embryogenesis	O
+[	O
+6	O
+-	O
+9	O
+]	O
+.	O
+
+Depletion	O
+of	O
+DHC	O
+-	O
+1	O
+by	O
+RNA	O
+interference	O
+(	O
+RNAi	O
+)	O
+in	O
+early	O
+C	B
+.	I
+elegans	I
+embryos	O
+produces	O
+defects	O
+in	O
+female	O
+meiotic	O
+divisions	O
+,	O
+migration	O
+of	O
+the	O
+oocyte	O
+and	O
+sperm	O
+pronuclei	O
+after	O
+fertilization	O
+,	O
+and	O
+centrosome	O
+separation	O
+during	O
+mitotic	O
+spindle	O
+assembly	O
+[	O
+6	O
+]	O
+.	O
+
+Analysis	O
+of	O
+fast	O
+-	O
+acting	O
+dhc	O
+-	O
+1	O
+temperature	O
+-	O
+sensitive	O
+(	O
+ts	O
+)	O
+mutants	O
+has	O
+further	O
+revealed	O
+that	O
+dynein	O
+is	O
+required	O
+for	O
+chromosome	O
+congression	O
+to	O
+the	O
+metaphase	O
+plate	O
+during	O
+mitosis	O
+,	O
+as	O
+well	O
+as	O
+for	O
+mitotic	O
+spindle	O
+positioning	O
+[	O
+10	O
+]	O
+.	O
+
+While	O
+many	O
+requirements	O
+for	O
+cytoplasmic	O
+dynein	O
+are	O
+known	O
+,	O
+our	O
+knowledge	O
+of	O
+the	O
+molecular	O
+mechanisms	O
+that	O
+target	O
+and	O
+regulate	O
+dynein	O
+remains	O
+limited	O
+.	O
+
+Clearly	O
+,	O
+the	O
+multiple	O
+ACs	O
+can	O
+couple	O
+the	O
+dynein	O
+HC	O
+to	O
+particular	O
+substrates	O
+[	O
+11	O
+]	O
+,	O
+including	O
+vesicles	O
+,	O
+nuclei	O
+,	O
+viruses	O
+,	O
+kinetochores	O
+,	O
+and	O
+rhodopsin	O
+[	O
+see	O
+table	O
+in	O
+1	O
+]	O
+.	O
+
+However	O
+,	O
+reducing	O
+the	O
+function	O
+of	O
+only	O
+four	O
+of	O
+the	O
+eleven	O
+dynein	O
+ACs	O
+in	O
+C	B
+.	I
+elegans	I
+produces	O
+lethal	O
+phenotypes	O
+[	O
+12	O
+]	O
+.	O
+
+Thus	O
+,	O
+it	O
+remains	O
+unclear	O
+how	O
+ACs	O
+influence	O
+the	O
+different	O
+essential	O
+requirements	O
+for	O
+dynein	O
+.	O
+
+Another	O
+potential	O
+route	O
+for	O
+dynein	O
+regulation	O
+involves	O
+the	O
+phosphorylation	O
+state	O
+of	O
+the	O
+different	O
+dynein	O
+chains	O
+,	O
+which	O
+in	O
+some	O
+cases	O
+confers	O
+distinctive	O
+functional	O
+properties	O
+to	O
+the	O
+motor	O
+.	O
+
+While	O
+many	O
+examples	O
+of	O
+dynein	O
+phosphorylation	O
+exist	O
+,	O
+and	O
+cell	O
+cycle	O
+dependent	O
+changes	O
+in	O
+phosphorylation	O
+have	O
+been	O
+described	O
+[	O
+13	O
+-	O
+15	O
+]	O
+,	O
+few	O
+if	O
+any	O
+studies	O
+have	O
+demonstrated	O
+a	O
+requirement	O
+for	O
+such	O
+modification	O
+during	O
+mitosis	O
+.	O
+
+Large	O
+-	O
+scale	O
+forward	O
+genetic	O
+screens	O
+have	O
+identified	O
+genes	O
+with	O
+requirements	O
+similar	O
+to	O
+those	O
+for	O
+dynein	O
+,	O
+but	O
+many	O
+of	O
+these	O
+encode	O
+core	O
+components	O
+of	O
+the	O
+microtubule	O
+cytoskeleton	O
+and	O
+few	O
+are	O
+known	O
+to	O
+directly	O
+influence	O
+dynein	O
+itself	O
+[	O
+12	O
+,	O
+16	O
+]	O
+.	O
+
+Genes	O
+that	O
+do	O
+influence	O
+dynein	O
+function	O
+might	O
+also	O
+have	O
+other	O
+essential	O
+roles	O
+,	O
+leading	O
+to	O
+pleiotropic	O
+mutant	O
+phenotypes	O
+that	O
+obscure	O
+their	O
+relationship	O
+to	O
+dynein	O
+[	O
+17	O
+-	O
+19	O
+]	O
+.	O
+
+Moreover	O
+,	O
+redundancy	O
+within	O
+the	O
+multigene	O
+dynein	O
+subunit	O
+families	O
+,	O
+and	O
+also	O
+perhaps	O
+between	O
+the	O
+different	O
+ACs	O
+,	O
+may	O
+complicate	O
+the	O
+identification	O
+of	O
+single	O
+gene	O
+requirements	O
+that	O
+are	O
+important	O
+for	O
+dynein	O
+function	O
+.	O
+
+Thus	O
+far	O
+,	O
+reducing	O
+the	O
+function	O
+of	O
+individual	O
+genes	O
+has	O
+not	O
+provided	O
+substantial	O
+insight	O
+into	O
+the	O
+mechanisms	O
+that	O
+regulate	O
+and	O
+mediate	O
+the	O
+many	O
+different	O
+requirements	O
+for	O
+cytoplasmic	O
+dynein	O
+during	O
+mitosis	O
+.	O
+
+To	O
+identify	O
+potential	O
+regulators	O
+of	O
+cytoplasmic	O
+dynein	O
+,	O
+we	O
+have	O
+used	O
+a	O
+sensitized	O
+genetic	O
+background	O
+to	O
+conduct	O
+a	O
+genome	O
+-	O
+wide	O
+screen	O
+for	O
+modifiers	O
+of	O
+dynein	O
+function	O
+in	O
+C	B
+.	I
+elegans	I
+.	O
+
+Other	O
+groups	O
+have	O
+successfully	O
+used	O
+RNAi	O
+modifier	O
+screens	O
+to	O
+identify	O
+genes	O
+that	O
+function	O
+in	O
+particular	O
+pathways	O
+[	O
+20	O
+-	O
+23	O
+]	O
+;	O
+we	O
+have	O
+used	O
+RNAi	O
+to	O
+screen	O
+for	O
+genes	O
+that	O
+,	O
+when	O
+reduced	O
+in	O
+function	O
+,	O
+suppress	O
+the	O
+embryonic	O
+lethality	O
+associated	O
+with	O
+a	O
+temperature	O
+-	O
+sensitive	O
+(	O
+ts	O
+)	O
+allele	O
+of	O
+the	O
+dhc	O
+-	O
+1	O
+dynein	O
+HC	O
+gene	O
+.	O
+
+Using	O
+the	O
+dhc	O
+-	O
+1ts	O
+genetic	O
+background	O
+,	O
+we	O
+found	O
+49	O
+genes	O
+that	O
+,	O
+when	O
+depleted	O
+,	O
+suppress	O
+the	O
+partial	O
+loss	O
+of	O
+HC	O
+function	O
+.	O
+
+Twenty	O
+of	O
+these	O
+genes	O
+suppress	O
+conditional	O
+dynein	O
+HC	O
+mutants	O
+but	O
+not	O
+other	O
+conditional	O
+mutants	O
+with	O
+unrelated	O
+defects	O
+.	O
+
+Finally	O
+,	O
+we	O
+show	O
+that	O
+some	O
+of	O
+these	O
+dynein	O
+-	O
+specific	O
+suppressors	O
+encode	O
+proteins	O
+that	O
+may	O
+overlap	O
+with	O
+the	O
+dynein	O
+HC	O
+in	O
+subcellular	O
+localization	O
+.	O
+
+Results	O
+
+To	O
+identify	O
+dynein	O
+suppressors	O
+,	O
+we	O
+used	O
+three	O
+different	O
+conditional	O
+and	O
+recessive	O
+dhc	O
+-	O
+1	O
+mutants	O
+that	O
+were	O
+identified	O
+previously	O
+[	O
+7	O
+]	O
+.	O
+
+These	O
+ts	O
+alleles	O
+of	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+,	O
+or283	O
+,	O
+and	O
+or352	O
+)	O
+produce	O
+similar	O
+defects	O
+at	O
+the	O
+restrictive	O
+temperature	O
+of	O
+26	O
+degrees	O
+C	O
+,	O
+including	O
+incomplete	O
+mitotic	O
+spindle	O
+assembly	O
+in	O
+one	O
+-	O
+cell	O
+embryos	O
+and	O
+embryonic	O
+lethality	O
+[	O
+7	O
+]	O
+.	O
+
+We	O
+sequenced	O
+the	O
+dhc	O
+-	O
+1	O
+locus	O
+in	O
+the	O
+three	O
+mutants	O
+.	O
+
+The	O
+independently	O
+isolated	O
+or195	O
+and	O
+or283	O
+alleles	O
+each	O
+change	O
+a	O
+conserved	O
+serine	O
+to	O
+leucine	O
+at	O
+codon	O
+3200	O
+,	O
+within	O
+the	O
+coiled	O
+-	O
+coil	O
+region	O
+of	O
+the	O
+microtubule	O
+-	O
+binding	O
+stalk	O
+domain	O
+(	O
+Figure	O
+1A	O
+and	O
+1C	O
+)	O
+.	O
+
+The	O
+or352	O
+allele	O
+replaces	O
+a	O
+conserved	O
+glycine	O
+with	O
+aspartic	O
+acid	O
+at	O
+codon	O
+2158	O
+,	O
+in	O
+the	O
+ATP	O
+-	O
+binding	O
+walker	O
+A	O
+motif	O
+of	O
+the	O
+second	O
+AAA	O
+ATPase	O
+domain	O
+(	O
+Figure	O
+1B	O
+and	O
+1C	O
+)	O
+.	O
+
+As	O
+both	O
+missense	O
+mutations	O
+affect	O
+conserved	O
+residues	O
+,	O
+they	O
+may	O
+prove	O
+useful	O
+for	O
+engineering	O
+ts	O
+alleles	O
+in	O
+other	O
+organisms	O
+.	O
+
+The	O
+temperature	O
+versus	O
+viability	O
+curves	O
+of	O
+the	O
+dynein	O
+ts	O
+mutants	O
+feature	O
+a	O
+steep	O
+central	O
+transition	O
+zone	O
+ideal	O
+for	O
+modifier	O
+screening	O
+because	O
+subtle	O
+changes	O
+in	O
+temperature	O
+produce	O
+large	O
+changes	O
+in	O
+embryonic	O
+viability	O
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+To	O
+identify	O
+genes	O
+that	O
+,	O
+when	O
+reduced	O
+in	O
+function	O
+,	O
+can	O
+suppress	O
+conditional	O
+dhc	O
+-	O
+1	O
+mutants	O
+,	O
+we	O
+developed	O
+a	O
+high	O
+-	O
+throughput	O
+RNAi	O
+-	O
+based	O
+screen	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+To	O
+reduce	O
+gene	O
+function	O
+we	O
+used	O
+a	O
+library	O
+of	O
+16	O
+,	O
+757	O
+bacterial	O
+strains	O
+that	O
+each	O
+express	O
+a	O
+dsRNA	O
+corresponding	O
+to	O
+exon	O
+-	O
+rich	O
+gene	O
+sequences	O
+[	O
+17	O
+,	O
+19	O
+]	O
+.	O
+
+We	O
+then	O
+tested	O
+over	O
+99	O
+%	O
+of	O
+the	O
+bacterial	O
+strains	O
+in	O
+this	O
+library	O
+for	O
+RNAi	O
+-	O
+mediated	O
+suppression	O
+of	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+embryonic	O
+lethality	O
+at	O
+23	O
+degrees	O
+C	O
+,	O
+after	O
+raising	O
+synchronized	O
+L1	O
+larvae	O
+to	O
+adulthood	O
+on	O
+dsRNA	O
+-	O
+expressing	O
+bacterial	O
+lawns	O
+in	O
+48	O
+-	O
+well	O
+agar	O
+plates	O
+.	O
+
+This	O
+screening	O
+procedure	O
+should	O
+work	O
+to	O
+identify	O
+nonessential	O
+and	O
+essential	O
+suppressor	O
+genes	O
+,	O
+because	O
+RNAi	O
+does	O
+not	O
+always	O
+fully	O
+reduce	O
+gene	O
+function	O
+[	O
+24	O
+,	O
+25	O
+]	O
+,	O
+and	O
+even	O
+if	O
+RNAi	O
+does	O
+produce	O
+lethality	O
+,	O
+cosuppression	O
+could	O
+restore	O
+viability	O
+.	O
+
+Nevertheless	O
+,	O
+essential	O
+genes	O
+may	O
+be	O
+missed	O
+due	O
+to	O
+earlier	O
+requirements	O
+that	O
+produce	O
+strong	O
+larval	O
+arrest	O
+,	O
+sterile	O
+,	O
+or	O
+embryonic	O
+lethal	O
+phenotypes	O
+.	O
+
+Using	O
+this	O
+screening	O
+procedure	O
+,	O
+we	O
+identified	O
+49	O
+bacterial	O
+clones	O
+that	O
+consistently	O
+increased	O
+embryonic	O
+viability	O
+at	O
+the	O
+semipermissive	O
+temperature	O
+.	O
+
+The	O
+dsRNA	O
+-	O
+producing	O
+plasmids	O
+were	O
+then	O
+sequenced	O
+to	O
+verify	O
+gene	O
+identity	O
+.	O
+
+Quantification	O
+of	O
+embryonic	O
+viability	O
+using	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+animals	O
+showed	O
+that	O
+the	O
+RNAi	O
+-	O
+mediated	O
+depletion	O
+of	O
+suppressor	O
+gene	O
+function	O
+increased	O
+viability	O
+to	O
+5	O
+%	O
+-	O
+100	O
+%	O
+,	O
+compared	O
+to	O
+less	O
+than	O
+2	O
+%	O
+in	O
+unsuppressed	O
+controls	O
+(	O
+Figure	O
+3A	O
+;	O
+Table	O
+S1	O
+)	O
+.	O
+
+The	O
+proteins	O
+encoded	O
+by	O
+the	O
+suppressor	O
+genes	O
+we	O
+identified	O
+are	O
+summarized	O
+in	O
+Figure	O
+4	O
+.	O
+
+As	O
+a	O
+more	O
+direct	O
+assay	O
+for	O
+dynein	O
+activity	O
+in	O
+the	O
+suppressed	O
+dhc	O
+-	O
+1	O
+embryos	O
+,	O
+we	O
+measured	O
+spindle	O
+length	O
+and	O
+cytokinesis	O
+success	O
+:	O
+dhc	O
+-	O
+1	O
+mutant	O
+embryos	O
+have	O
+severe	O
+spindle	O
+assembly	O
+defects	O
+and	O
+subsequent	O
+cytokinesis	O
+failures	O
+[	O
+6	O
+,	O
+7	O
+,	O
+10	O
+]	O
+.	O
+
+We	O
+shifted	O
+dhc	O
+-	O
+1	O
+adult	O
+hermaphrodites	O
+from	O
+23	O
+degrees	O
+C	O
+to	O
+the	O
+fully	O
+restrictive	O
+temperature	O
+of	O
+26	O
+degrees	O
+C	O
+for	O
+3	O
+-	O
+5	O
+hours	O
+and	O
+made	O
+time	O
+-	O
+lapse	O
+video	O
+micrographs	O
+using	O
+Nomarski	O
+optics	O
+to	O
+monitor	O
+the	O
+first	O
+embryonic	O
+cell	O
+division	O
+.	O
+
+This	O
+procedure	O
+results	O
+in	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+embryos	O
+with	O
+P0	O
+spindles	O
+30	O
+%	O
+the	O
+length	O
+of	O
+wild	O
+-	O
+type	O
+spindles	O
+(	O
+Figure	O
+S1	O
+)	O
+.	O
+
+In	O
+the	O
+suppressed	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+backgrounds	O
+,	O
+spindle	O
+lengths	O
+ranged	O
+from	O
+30	O
+%	O
+-	O
+83	O
+%	O
+of	O
+wild	O
+-	O
+type	O
+lengths	O
+(	O
+Figure	O
+S1	O
+)	O
+.	O
+
+Similarly	O
+,	O
+cytokinesis	O
+failed	O
+in	O
+unsuppressed	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+embryos	O
+89	O
+%	O
+of	O
+the	O
+time	O
+,	O
+but	O
+most	O
+of	O
+the	O
+suppressors	O
+rescued	O
+this	O
+phenotype	O
+(	O
+Figure	O
+S1	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+most	O
+of	O
+the	O
+suppressors	O
+influence	O
+dynein	O
+-	O
+dependent	O
+cellular	O
+processes	O
+,	O
+as	O
+expected	O
+given	O
+their	O
+ability	O
+to	O
+restore	O
+viability	O
+when	O
+reduced	O
+in	O
+function	O
+.	O
+
+Specificity	O
+of	O
+Suppression	O
+
+Because	O
+RNAi	O
+can	O
+reduce	O
+the	O
+function	O
+of	O
+unintended	O
+targets	O
+(	O
+so	O
+-	O
+called	O
+"	O
+off	O
+-	O
+target	O
+effects	O
+"	O
+[	O
+26	O
+,	O
+27	O
+]	O
+)	O
+,	O
+we	O
+also	O
+used	O
+available	O
+mutations	O
+in	O
+some	O
+of	O
+the	O
+suppressor	O
+genes	O
+we	O
+identified	O
+to	O
+reduce	O
+their	O
+function	O
+.	O
+
+We	O
+constructed	O
+double	O
+mutant	O
+strains	O
+using	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+and	O
+viable	O
+deletion	O
+alleles	O
+for	O
+two	O
+suppressor	O
+genes	O
+,	O
+dylt	O
+-	O
+1	O
+(	O
+ok417	O
+)	O
+and	O
+ufd	O
+-	O
+2	O
+(	O
+tm1380	O
+)	O
+,	O
+and	O
+examined	O
+embryonic	O
+viability	O
+(	O
+Figure	O
+3B	O
+)	O
+.	O
+
+The	O
+deletion	O
+alleles	O
+of	O
+dylt	O
+-	O
+1	O
+(	O
+encoding	O
+a	O
+Tctex1	O
+-	O
+type	O
+dynein	O
+light	O
+chain	O
+)	O
+,	O
+and	O
+ufd	O
+-	O
+2	O
+(	O
+encoding	O
+a	O
+ubiquitin	O
+conjugating	O
+enzyme	O
+)	O
+both	O
+recapitulated	O
+the	O
+suppression	O
+produced	O
+by	O
+RNAi	O
+knockdown	O
+(	O
+Figure	O
+3B	O
+)	O
+.	O
+
+The	O
+dpy	O
+-	O
+3	O
+(	O
+e27	O
+)	O
+and	O
+dpy	O
+-	O
+10	O
+(	O
+e128	O
+)	O
+point	O
+mutation	O
+alleles	O
+[	O
+28	O
+]	O
+also	O
+suppressed	O
+embryonic	O
+lethality	O
+in	O
+double	O
+mutants	O
+(	O
+Figure	O
+3B	O
+)	O
+.	O
+
+Based	O
+on	O
+this	O
+small	O
+sampling	O
+,	O
+and	O
+because	O
+RNAi	O
+in	O
+C	B
+.	I
+elegans	I
+appears	O
+to	O
+be	O
+highly	O
+gene	O
+specific	O
+in	O
+the	O
+absence	O
+of	O
+close	O
+paralogs	O
+[	O
+12	O
+,	O
+19	O
+]	O
+,	O
+we	O
+conclude	O
+that	O
+many	O
+of	O
+the	O
+suppressors	O
+we	O
+have	O
+identified	O
+will	O
+prove	O
+to	O
+be	O
+suppressor	O
+locus	O
+specific	O
+.	O
+
+The	O
+dsRNA	O
+-	O
+expressing	O
+bacterial	O
+clones	O
+we	O
+used	O
+to	O
+deplete	O
+two	O
+of	O
+the	O
+dynein	O
+suppressors	O
+(	O
+tag	O
+-	O
+300	O
+and	O
+ZK1127	O
+.	O
+10	O
+)	O
+probably	O
+also	O
+knock	O
+down	O
+expression	O
+of	O
+one	O
+close	O
+paralog	O
+for	O
+each	O
+locus	O
+[	O
+29	O
+]	O
+.	O
+
+We	O
+next	O
+asked	O
+whether	O
+the	O
+suppressors	O
+are	O
+specific	O
+for	O
+dynein	O
+function	O
+or	O
+if	O
+their	O
+depletion	O
+more	O
+generally	O
+stabilizes	O
+ts	O
+proteins	O
+.	O
+
+We	O
+tested	O
+for	O
+specificity	O
+using	O
+two	O
+conditional	O
+mutants	O
+with	O
+cell	O
+fate	O
+patterning	O
+defects	O
+unrelated	O
+to	O
+dynein	O
+function	O
+,	O
+lit	O
+-	O
+1	O
+(	O
+or131	O
+)	O
+and	O
+spn	O
+-	O
+4	O
+(	O
+or191	O
+)	O
+.	O
+
+The	O
+lit	O
+-	O
+1	O
+gene	O
+encodes	O
+a	O
+MAP	O
+kinase	O
+-	O
+related	O
+protein	O
+[	O
+30	O
+]	O
+,	O
+while	O
+spn	O
+-	O
+4	O
+encodes	O
+a	O
+protein	O
+with	O
+an	O
+RNA	O
+binding	O
+motif	O
+[	O
+31	O
+]	O
+.	O
+
+We	O
+found	O
+that	O
+ten	O
+of	O
+the	O
+dhc	O
+-	O
+1	O
+-	O
+interacting	O
+genes	O
+significantly	O
+increased	O
+embryonic	O
+viability	O
+in	O
+both	O
+lit	O
+-	O
+1	O
+and	O
+spn	O
+-	O
+4	O
+mutants	O
+,	O
+while	O
+18	O
+others	O
+suppressed	O
+one	O
+or	O
+the	O
+other	O
+of	O
+these	O
+two	O
+conditional	O
+mutants	O
+when	O
+reduced	O
+in	O
+function	O
+using	O
+the	O
+same	O
+RNAi	O
+protocol	O
+as	O
+that	O
+used	O
+for	O
+dhc	O
+-	O
+1ts	O
+mutants	O
+(	O
+Figure	O
+4	O
+,	O
+right	O
+two	O
+columns	O
+;	O
+Table	O
+S1	O
+)	O
+.	O
+
+Therefore	O
+,	O
+about	O
+half	O
+of	O
+the	O
+suppressors	O
+appear	O
+to	O
+act	O
+nonspecifically	O
+on	O
+multiple	O
+ts	O
+mutants	O
+to	O
+restore	O
+embryonic	O
+viability	O
+.	O
+
+From	O
+here	O
+on	O
+,	O
+we	O
+will	O
+refer	O
+to	O
+the	O
+suppressors	O
+that	O
+only	O
+acted	O
+on	O
+dhc	O
+-	O
+1	O
+,	O
+and	O
+not	O
+on	O
+lit	O
+-	O
+1	O
+and	O
+spn	O
+-	O
+4	O
+ts	O
+mutants	O
+,	O
+as	O
+dynein	O
+-	O
+specific	O
+suppressors	O
+.	O
+
+Because	O
+many	O
+ts	O
+mutations	O
+exert	O
+their	O
+effect	O
+via	O
+protein	O
+assembly	O
+or	O
+unfolding	O
+mechanisms	O
+[	O
+32	O
+]	O
+,	O
+suppressor	O
+genes	O
+reduced	O
+in	O
+function	O
+by	O
+RNAi	O
+might	O
+not	O
+be	O
+expected	O
+to	O
+exhibit	O
+allele	O
+specificity	O
+with	O
+most	O
+ts	O
+mutations	O
+.	O
+
+To	O
+determine	O
+if	O
+the	O
+dynein	O
+suppressors	O
+are	O
+either	O
+allele	O
+or	O
+strain	O
+specific	O
+,	O
+we	O
+tested	O
+the	O
+two	O
+other	O
+conditional	O
+dhc	O
+-	O
+1	O
+strains	O
+(	O
+containing	O
+the	O
+or283	O
+and	O
+or352	O
+alleles	O
+)	O
+.	O
+
+Although	O
+the	O
+or283	O
+allele	O
+is	O
+identical	O
+to	O
+or195	O
+,	O
+it	O
+provides	O
+a	O
+useful	O
+control	O
+for	O
+the	O
+presence	O
+of	O
+background	O
+mutations	O
+because	O
+the	O
+two	O
+strains	O
+were	O
+isolated	O
+independently	O
+.	O
+
+In	O
+most	O
+cases	O
+,	O
+depletion	O
+of	O
+the	O
+dynein	O
+-	O
+specific	O
+suppressors	O
+also	O
+restored	O
+viability	O
+to	O
+the	O
+other	O
+two	O
+ts	O
+dhc	O
+-	O
+1	O
+alleles	O
+.	O
+
+Y40B1B	O
+.	O
+5	O
+,	O
+a	O
+putative	O
+translation	O
+initiation	O
+factor	O
+,	O
+suppressed	O
+only	O
+one	O
+conditional	O
+dhc	O
+-	O
+1	O
+strain	O
+,	O
+and	O
+we	O
+consider	O
+this	O
+as	O
+an	O
+example	O
+of	O
+a	O
+nonspecific	O
+interaction	O
+(	O
+Figure	O
+4	O
+,	O
+left	O
+three	O
+columns	O
+;	O
+Table	O
+S1	O
+)	O
+.	O
+
+Two	O
+dsRNAs	O
+that	O
+do	O
+not	O
+suppress	O
+lit	O
+-	O
+1	O
+or	O
+spn	O
+-	O
+4	O
+mutants	O
+produced	O
+suppression	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+and	O
+dhc	O
+-	O
+1	O
+(	O
+or283	O
+)	O
+strains	O
+,	O
+but	O
+not	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or352	O
+)	O
+strain	O
+,	O
+perhaps	O
+indicating	O
+allele	O
+specificity	O
+or	O
+variability	O
+in	O
+the	O
+RNAi	O
+treatments	O
+.	O
+
+We	O
+conclude	O
+that	O
+strain	O
+background	O
+differences	O
+are	O
+relatively	O
+rare	O
+,	O
+and	O
+that	O
+the	O
+majority	O
+of	O
+the	O
+suppressors	O
+are	O
+allele	O
+-	O
+independent	O
+.	O
+
+To	O
+summarize	O
+,	O
+we	O
+have	O
+identified	O
+20	O
+genes	O
+that	O
+when	O
+reduced	O
+in	O
+function	O
+specifically	O
+suppress	O
+multiple	O
+dynein	O
+ts	O
+strains	O
+but	O
+not	O
+unrelated	O
+ts	O
+loci	O
+.	O
+
+Survey	O
+of	O
+Putative	O
+Dynein	O
+Accessory	O
+Chains	O
+
+We	O
+were	O
+surprised	O
+to	O
+discover	O
+that	O
+depleting	O
+two	O
+predicted	O
+dynein	O
+ACs	O
+specifically	O
+suppressed	O
+the	O
+partial	O
+loss	O
+of	O
+HC	O
+function	O
+,	O
+because	O
+most	O
+dynein	O
+accessory	O
+subunits	O
+are	O
+presumed	O
+to	O
+promote	O
+dynein	O
+function	O
+by	O
+aiding	O
+dynein	O
+complex	O
+formation	O
+or	O
+mediating	O
+cargo	O
+attachment	O
+[	O
+3	O
+,	O
+11	O
+,	O
+33	O
+]	O
+.	O
+
+Depletion	O
+of	O
+either	O
+dylt	O
+-	O
+1	O
+(	O
+encoding	O
+a	O
+Tctex1	O
+-	O
+type	O
+light	O
+chain	O
+)	O
+or	O
+dyrb	O
+-	O
+1	O
+(	O
+encoding	O
+a	O
+roadblock	O
+-	O
+type	O
+light	O
+chain	O
+)	O
+suppressed	O
+embryonic	O
+lethality	O
+in	O
+all	O
+three	O
+ts	O
+dynein	O
+HC	O
+mutant	O
+strains	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+To	O
+extend	O
+this	O
+observation	O
+,	O
+we	O
+surveyed	O
+all	O
+genes	O
+encoding	O
+predicted	O
+dynein	O
+components	O
+for	O
+suppression	O
+of	O
+the	O
+three	O
+ts	O
+dhc	O
+-	O
+1	O
+mutants	O
+(	O
+Figure	O
+5A	O
+;	O
+Table	O
+S2	O
+)	O
+.	O
+
+We	O
+reasoned	O
+that	O
+some	O
+dynein	O
+subunit	O
+genes	O
+could	O
+have	O
+been	O
+missed	O
+in	O
+the	O
+primary	O
+screening	O
+and	O
+several	O
+dynein	O
+AC	O
+genes	O
+were	O
+not	O
+represented	O
+in	O
+the	O
+E	B
+.	I
+coli	I
+RNAi	O
+library	O
+.	O
+
+After	O
+using	O
+RNAi	O
+to	O
+reduce	O
+their	O
+function	O
+,	O
+we	O
+found	O
+that	O
+one	O
+of	O
+three	O
+Tctex1	O
+homologs	O
+(	O
+dylt	O
+-	O
+1	O
+)	O
+,	O
+one	O
+of	O
+four	O
+LC8	O
+homologs	O
+(	O
+dlc	O
+-	O
+1	O
+)	O
+,	O
+one	O
+of	O
+two	O
+light	O
+intermediate	O
+chains	O
+(	O
+dli	O
+-	O
+1	O
+)	O
+,	O
+as	O
+well	O
+as	O
+the	O
+sole	O
+roadblock	O
+homolog	O
+(	O
+dyrb	O
+-	O
+1	O
+)	O
+each	O
+strongly	O
+suppressed	O
+the	O
+three	O
+conditional	O
+dynein	O
+mutants	O
+.	O
+
+Lower	O
+-	O
+level	O
+suppression	O
+was	O
+also	O
+seen	O
+for	O
+the	O
+second	O
+light	O
+intermediate	O
+chain	O
+,	O
+xbx	O
+-	O
+1	O
+,	O
+when	O
+its	O
+function	O
+was	O
+reduced	O
+.	O
+
+Thus	O
+,	O
+one	O
+gene	O
+of	O
+each	O
+of	O
+four	O
+subunit	O
+classes	O
+restores	O
+viability	O
+to	O
+the	O
+three	O
+dhc	O
+-	O
+1	O
+mutant	O
+strains	O
+when	O
+depleted	O
+by	O
+RNAi	O
+.	O
+
+The	O
+only	O
+subunit	O
+class	O
+not	O
+found	O
+to	O
+suppress	O
+was	O
+the	O
+intermediate	O
+chain	O
+,	O
+encoded	O
+by	O
+a	O
+single	O
+gene	O
+in	O
+C	B
+.	I
+elegans	I
+,	O
+dyci	O
+-	O
+1	O
+.	O
+
+When	O
+reduced	O
+in	O
+function	O
+by	O
+RNAi	O
+,	O
+dyci	O
+-	O
+1	O
+produces	O
+a	O
+larval	O
+arrest	O
+phenotype	O
+like	O
+that	O
+observed	O
+for	O
+dhc	O
+-	O
+1	O
+(	O
+RNAi	O
+)	O
+;	O
+this	O
+phenotype	O
+precludes	O
+any	O
+suppression	O
+of	O
+the	O
+conditional	O
+embryonic	O
+lethality	O
+(	O
+shown	O
+as	O
+"	O
+la	O
+"	O
+in	O
+Figure	O
+5A	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+knockdown	O
+of	O
+either	O
+dlc	O
+-	O
+1	O
+or	O
+dli	O
+-	O
+1	O
+suppresses	O
+embryonic	O
+lethality	O
+in	O
+the	O
+dhc	O
+-	O
+1ts	O
+mutants	O
+,	O
+even	O
+though	O
+reducing	O
+their	O
+function	O
+in	O
+otherwise	O
+wild	O
+-	O
+type	O
+embryos	O
+produces	O
+dhc	O
+-	O
+1	O
+-	O
+like	O
+defects	O
+,	O
+including	O
+embryonic	O
+lethality	O
+[	O
+12	O
+,	O
+34	O
+]	O
+(	O
+see	O
+Figure	O
+5B	O
+and	O
+Discussion	O
+)	O
+.	O
+
+The	O
+suppressing	O
+cytoplasmic	O
+dynein	O
+subunits	O
+and	O
+DYCI	O
+-	O
+1	O
+are	O
+shown	O
+in	O
+a	O
+putative	O
+complex	O
+in	O
+Figure	O
+5E	O
+.	O
+
+We	O
+performed	O
+several	O
+genetic	O
+assays	O
+to	O
+better	O
+understand	O
+how	O
+the	O
+suppressor	O
+genes	O
+may	O
+be	O
+operating	O
+.	O
+
+First	O
+,	O
+suppression	O
+of	O
+dhc	O
+-	O
+1	O
+lethality	O
+by	O
+reducing	O
+AC	O
+function	O
+may	O
+indicate	O
+that	O
+our	O
+dhc	O
+-	O
+1	O
+alleles	O
+express	O
+a	O
+neomorphic	O
+and	O
+toxic	O
+DHC	O
+-	O
+1	O
+protein	O
+:	O
+if	O
+the	O
+suppressor	O
+dynein	O
+AC	O
+subunits	O
+positively	O
+function	O
+in	O
+dynein	O
+processes	O
+,	O
+depleting	O
+them	O
+might	O
+suppress	O
+any	O
+neomorphic	O
+effects	O
+.	O
+
+This	O
+explanation	O
+is	O
+perhaps	O
+unlikely	O
+,	O
+because	O
+the	O
+dhc	O
+-	O
+1ts	O
+alleles	O
+are	O
+all	O
+recessive	O
+,	O
+but	O
+remained	O
+a	O
+possibility	O
+in	O
+dhc	O
+-	O
+1	O
+homozygotes	O
+.	O
+
+We	O
+therefore	O
+reduced	O
+dynein	O
+function	O
+using	O
+RNAi	O
+in	O
+animals	O
+that	O
+had	O
+passed	O
+through	O
+the	O
+larval	O
+arrest	O
+points	O
+for	O
+dhc	O
+-	O
+1	O
+(	O
+RNAi	O
+)	O
+and	O
+dyci	O
+-	O
+1	O
+(	O
+RNAi	O
+)	O
+.	O
+
+Specifically	O
+,	O
+we	O
+transferred	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+L4	O
+hermaphrodites	O
+to	O
+plates	O
+with	O
+bacteria	O
+expressing	O
+dhc	O
+-	O
+1	O
+or	O
+dyci	O
+-	O
+1	O
+dsRNA	O
+.	O
+
+As	O
+control	O
+we	O
+performed	O
+dylt	O
+-	O
+1	O
+(	O
+RNAi	O
+)	O
+using	O
+the	O
+same	O
+procedure	O
+.	O
+
+We	O
+observed	O
+substantial	O
+suppression	O
+with	O
+dylt	O
+-	O
+1	O
+in	O
+this	O
+assay	O
+,	O
+but	O
+we	O
+saw	O
+no	O
+suppression	O
+with	O
+the	O
+heavy	O
+or	O
+intermediate	O
+chains	O
+(	O
+Figure	O
+5C	O
+)	O
+.	O
+
+This	O
+suggests	O
+that	O
+the	O
+DHC	O
+-	O
+1ts	O
+protein	O
+is	O
+not	O
+toxic	O
+and	O
+that	O
+dyci	O
+-	O
+1	O
+acts	O
+more	O
+like	O
+dhc	O
+-	O
+1	O
+than	O
+the	O
+other	O
+suppressing	O
+ACs	O
+because	O
+it	O
+does	O
+not	O
+suppress	O
+the	O
+heavy	O
+chain	O
+mutant	O
+.	O
+
+To	O
+further	O
+examine	O
+the	O
+nature	O
+of	O
+the	O
+AC	O
+suppression	O
+,	O
+we	O
+asked	O
+if	O
+depletion	O
+of	O
+the	O
+suppressor	O
+chains	O
+could	O
+bypass	O
+the	O
+requirement	O
+for	O
+dhc	O
+-	O
+1	O
+.	O
+
+We	O
+transferred	O
+wild	O
+-	O
+type	O
+L4	O
+larvae	O
+to	O
+plates	O
+with	O
+bacteria	O
+expressing	O
+dsRNA	O
+corresponding	O
+to	O
+both	O
+the	O
+suppressor	O
+ACs	O
+and	O
+dhc	O
+-	O
+1	O
+.	O
+
+We	O
+did	O
+not	O
+observe	O
+any	O
+suppression	O
+in	O
+these	O
+double	O
+RNAi	O
+assays	O
+(	O
+Figure	O
+5D	O
+)	O
+,	O
+suggesting	O
+that	O
+dhc	O
+-	O
+1ts	O
+suppression	O
+requires	O
+the	O
+residual	O
+activity	O
+of	O
+the	O
+defective	O
+DHC	O
+-	O
+1	O
+protein	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+dynein	O
+AC	O
+suppressors	O
+inhibit	O
+or	O
+somehow	O
+oppose	O
+the	O
+function	O
+of	O
+the	O
+DHC	O
+-	O
+1ts	O
+protein	O
+,	O
+and	O
+that	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195ts	O
+)	O
+mutation	O
+does	O
+not	O
+produce	O
+a	O
+toxic	O
+gene	O
+product	O
+but	O
+simply	O
+reduces	O
+DHC	O
+-	O
+1	O
+activity	O
+to	O
+a	O
+low	O
+,	O
+but	O
+non	O
+-	O
+null	O
+,	O
+level	O
+.	O
+
+Localization	O
+of	O
+the	O
+Dynein	O
+Suppressor	O
+Proteins	O
+
+To	O
+further	O
+explore	O
+how	O
+the	O
+suppressor	O
+proteins	O
+function	O
+,	O
+we	O
+examined	O
+the	O
+subcellular	O
+localization	O
+of	O
+nine	O
+of	O
+them	O
+as	O
+stably	O
+expressed	O
+N	O
+-	O
+terminal	O
+GFP	O
+:	O
+:	O
+S	O
+fusions	O
+.	O
+
+We	O
+chose	O
+to	O
+first	O
+focus	O
+on	O
+the	O
+suppressor	O
+genes	O
+that	O
+were	O
+conserved	O
+but	O
+poorly	O
+characterized	O
+in	O
+any	O
+system	O
+,	O
+or	O
+were	O
+conserved	O
+but	O
+uncharacterized	O
+during	O
+early	O
+C	B
+.	I
+elegans	I
+embryogenesis	O
+.	O
+
+Prior	O
+dynein	O
+immunocytochemistry	O
+-	O
+based	O
+localization	O
+studies	O
+serve	O
+as	O
+a	O
+comparison	O
+[	O
+6	O
+,	O
+10	O
+,	O
+35	O
+]	O
+.	O
+
+As	O
+in	O
+other	O
+species	O
+,	O
+C	B
+.	I
+elegans	I
+DHC	O
+-	O
+1	O
+is	O
+associated	O
+with	O
+mitotic	O
+spindles	O
+,	O
+centrosomes	O
+,	O
+the	O
+nuclear	O
+envelope	O
+,	O
+the	O
+cell	O
+cortex	O
+,	O
+the	O
+midbody	O
+,	O
+and	O
+throughout	O
+the	O
+cytoplasm	O
+.	O
+
+Most	O
+of	O
+the	O
+suppressor	O
+proteins	O
+we	O
+examined	O
+localized	O
+to	O
+sites	O
+where	O
+DHC	O
+-	O
+1	O
+is	O
+known	O
+to	O
+act	O
+or	O
+localize	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+nearly	O
+ubiquitous	O
+distribution	O
+of	O
+DHC	O
+-	O
+1	O
+in	O
+early	O
+embryonic	O
+cells	O
+makes	O
+colocalization	O
+likely	O
+but	O
+not	O
+necessarily	O
+meaningful	O
+,	O
+and	O
+biochemical	O
+studies	O
+are	O
+needed	O
+to	O
+conclusively	O
+address	O
+any	O
+direct	O
+or	O
+indirect	O
+physical	O
+associations	O
+.	O
+
+Four	O
+suppressor	O
+GFP	O
+fusion	O
+proteins	O
+localized	O
+to	O
+nuclear	O
+membranes	O
+and	O
+to	O
+spindle	O
+poles	O
+or	O
+pericentrosomal	O
+regions	O
+.	O
+
+The	O
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+dynein	O
+light	O
+chains	O
+were	O
+associated	O
+with	O
+nuclear	O
+envelopes	O
+and	O
+centrosomes	O
+,	O
+as	O
+well	O
+as	O
+meiotic	O
+and	O
+mitotic	O
+spindle	O
+poles	O
+(	O
+Figure	O
+6A	O
+-	O
+6H	O
+;	O
+Videos	O
+S1	O
+and	O
+S2	O
+)	O
+.	O
+
+The	O
+potential	O
+coiled	O
+-	O
+coil	O
+protein	O
+K04F10	O
+.	O
+3	O
+was	O
+present	O
+on	O
+the	O
+nuclear	O
+envelope	O
+and	O
+in	O
+a	O
+pericentrosomal	O
+position	O
+during	O
+mitosis	O
+,	O
+similar	O
+to	O
+endoplasmic	O
+reticulum	O
+proteins	O
+[	O
+36	O
+]	O
+(	O
+Figure	O
+6I	O
+-	O
+6L	O
+;	O
+Video	O
+S3	O
+)	O
+.	O
+
+K04F10	O
+.	O
+3	O
+was	O
+also	O
+highly	O
+enriched	O
+at	O
+meiotic	O
+spindle	O
+poles	O
+(	O
+Figure	O
+6I	O
+)	O
+,	O
+which	O
+has	O
+been	O
+observed	O
+for	O
+other	O
+endoplasmic	O
+reticulum	O
+proteins	O
+[	O
+36	O
+]	O
+.	O
+
+The	O
+NPP	O
+-	O
+22	O
+transmembrane	O
+nucleoporin	O
+was	O
+found	O
+at	O
+nuclear	O
+envelopes	O
+(	O
+Figure	O
+6M	O
+-	O
+6P	O
+;	O
+Video	O
+S4	O
+)	O
+,	O
+as	O
+previously	O
+reported	O
+for	O
+later	O
+stage	O
+embryos	O
+[	O
+37	O
+]	O
+,	O
+and	O
+it	O
+also	O
+surrounded	O
+centrosomes	O
+during	O
+mitosis	O
+.	O
+
+Two	O
+splice	O
+isoforms	O
+of	O
+the	O
+pleckstrin	O
+homology	O
+domain	O
+-	O
+containing	O
+EFA	O
+-	O
+6	O
+/	O
+Y55D9A	O
+.	O
+1	O
+,	O
+an	O
+ARF	O
+guanine	O
+nucleotide	O
+exchange	O
+factor	O
+,	O
+were	O
+enriched	O
+cortically	O
+both	O
+in	O
+the	O
+anterior	O
+portion	O
+of	O
+the	O
+one	O
+-	O
+cell	O
+zygote	O
+and	O
+at	O
+the	O
+blastomere	O
+boundary	O
+in	O
+two	O
+-	O
+cell	O
+embryos	O
+(	O
+Figure	O
+6Q	O
+-	O
+6T	O
+;	O
+Videos	O
+S5	O
+and	O
+S6	O
+)	O
+.	O
+
+The	O
+conserved	O
+Mo25	O
+homolog	O
+MOP	O
+-	O
+25	O
+.	O
+2	O
+/	O
+Y53C12A	O
+.	O
+4	O
+was	O
+found	O
+enriched	O
+in	O
+a	O
+single	O
+spot	O
+after	O
+cytokinesis	O
+that	O
+appears	O
+to	O
+correspond	O
+to	O
+the	O
+midbody	O
+(	O
+Figure	O
+6U	O
+-	O
+6X	O
+;	O
+Video	O
+S7	O
+)	O
+.	O
+
+F10E7	O
+.	O
+8	O
+,	O
+a	O
+highly	O
+conserved	O
+ortholog	O
+of	O
+S	B
+.	I
+cerevisiae	I
+Far11	O
+,	O
+appears	O
+nuclear	O
+(	O
+Figure	O
+6Y	O
+-	O
+6B	O
+'	O
+and	O
+Video	O
+S8	O
+)	O
+.	O
+
+Finally	O
+,	O
+the	O
+nonspecific	O
+suppressor	O
+protein	O
+STAR	O
+-	O
+2	O
+,	O
+a	O
+predicted	O
+RNA	O
+binding	O
+protein	O
+,	O
+appears	O
+to	O
+be	O
+associated	O
+with	O
+P	O
+-	O
+granules	O
+(	O
+like	O
+its	O
+homolog	O
+GLD	O
+-	O
+1	O
+)	O
+,	O
+where	O
+dynein	O
+is	O
+neither	O
+localized	O
+nor	O
+known	O
+to	O
+function	O
+(	O
+Figure	O
+6C	O
+'	O
+-	O
+6F	O
+'	O
+)	O
+.	O
+
+DLYT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+:	O
+Dynein	O
+Light	O
+Chain	O
+Localization	O
+
+The	O
+C	B
+.	I
+elegans	I
+dynein	O
+HC	O
+protein	O
+weakly	O
+localizes	O
+to	O
+spindle	O
+poles	O
+during	O
+early	O
+embryonic	O
+cell	O
+cycles	O
+[	O
+6	O
+,	O
+10	O
+]	O
+,	O
+and	O
+so	O
+did	O
+DYRB	O
+-	O
+1	O
+and	O
+DYLT	O
+-	O
+1	O
+(	O
+Videos	O
+S9	O
+and	O
+S10	O
+)	O
+.	O
+
+However	O
+,	O
+ts	O
+mutant	O
+forms	O
+of	O
+the	O
+DHC	O
+-	O
+1	O
+protein	O
+(	O
+including	O
+DHC	O
+-	O
+1	O
+encoded	O
+by	O
+the	O
+or195	O
+allele	O
+)	O
+strongly	O
+localize	O
+to	O
+centrosomes	O
+when	O
+shifted	O
+to	O
+the	O
+non	O
+-	O
+permissive	O
+temperature	O
+[	O
+10	O
+]	O
+.	O
+
+The	O
+mechanism	O
+underlying	O
+this	O
+enhanced	O
+localization	O
+is	O
+not	O
+known	O
+,	O
+but	O
+it	O
+may	O
+represent	O
+trapping	O
+of	O
+the	O
+defective	O
+protein	O
+at	O
+a	O
+normally	O
+transient	O
+location	O
+.	O
+
+We	O
+exploited	O
+this	O
+behavior	O
+of	O
+the	O
+mutant	O
+DHC	O
+-	O
+1	O
+protein	O
+to	O
+determine	O
+whether	O
+redistribution	O
+of	O
+the	O
+putative	O
+DYRB	O
+-	O
+1	O
+and	O
+DYLT	O
+-	O
+1	O
+dynein	O
+light	O
+chains	O
+also	O
+occurred	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+background	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+cellular	O
+distributions	O
+of	O
+DYRB	O
+-	O
+1	O
+and	O
+DYLT	O
+-	O
+1	O
+were	O
+dramatically	O
+altered	O
+in	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+mutant	O
+embryos	O
+.	O
+
+After	O
+shifting	O
+the	O
+parental	O
+worms	B
+to	O
+the	O
+restrictive	O
+temperature	O
+for	O
+3	O
+-	O
+5	O
+h	O
+prior	O
+to	O
+collecting	O
+embryos	O
+,	O
+these	O
+two	O
+proteins	O
+were	O
+prominently	O
+localized	O
+to	O
+centrosomes	O
+and	O
+to	O
+spindle	O
+poles	O
+that	O
+did	O
+not	O
+separate	O
+in	O
+one	O
+-	O
+cell	O
+stage	O
+embryos	O
+(	O
+Figure	O
+7	O
+;	O
+Videos	O
+S11	O
+and	O
+S12	O
+)	O
+.	O
+
+The	O
+spindle	O
+pole	O
+to	O
+cytoplasmic	O
+fluorescence	O
+ratio	O
+during	O
+late	O
+anaphase	O
+was	O
+5	O
+-	O
+fold	O
+higher	O
+in	O
+both	O
+of	O
+the	O
+dhc	O
+-	O
+1	O
+homozygous	O
+mutant	O
+strains	O
+when	O
+compared	O
+to	O
+wild	O
+-	O
+type	O
+embryos	O
+expressing	O
+the	O
+GFP	O
+fusions	O
+.	O
+
+We	O
+also	O
+assayed	O
+localization	O
+of	O
+the	O
+two	O
+putative	O
+dynein	O
+light	O
+chains	O
+after	O
+short	O
+temperature	O
+shifts	O
+to	O
+the	O
+nonpermissive	O
+temperature	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+mutant	O
+background	O
+,	O
+which	O
+yields	O
+mitotic	O
+spindles	O
+with	O
+an	O
+overall	O
+wild	O
+-	O
+type	O
+appearance	O
+and	O
+function	O
+.	O
+
+These	O
+short	O
+temperature	O
+shifts	O
+also	O
+resulted	O
+in	O
+robust	O
+localization	O
+of	O
+these	O
+two	O
+dynein	O
+light	O
+chains	O
+to	O
+centrosomes	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+Finally	O
+,	O
+we	O
+examined	O
+the	O
+localization	O
+of	O
+GFP	O
+:	O
+:	O
+DYRB	O
+-	O
+1	O
+and	O
+GFP	O
+:	O
+:	O
+DYLT	O
+-	O
+1	O
+in	O
+embryos	O
+from	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+-	O
+/	O
++	O
+worms	B
+grown	O
+at	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+permissive	O
+temperature	O
+of	O
+15	O
+degrees	O
+C	O
+.	O
+
+Even	O
+though	O
+embryos	O
+from	O
+mothers	O
+heterozygous	O
+for	O
+this	O
+recessive	O
+mutation	O
+are	O
+viable	O
+and	O
+develop	O
+normally	O
+,	O
+even	O
+at	O
+26	O
+degrees	O
+C	O
+[	O
+7	O
+]	O
+,	O
+we	O
+observed	O
+a	O
+substantial	O
+increase	O
+in	O
+both	O
+GFP	O
+fusion	O
+proteins	O
+at	O
+the	O
+mitotic	O
+spindle	O
+poles	O
+in	O
+early	O
+embryos	O
+(	O
+Figure	O
+7	O
+;	O
+Videos	O
+S13	O
+and	O
+S14	O
+)	O
+.	O
+
+Importantly	O
+,	O
+localization	O
+of	O
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+to	O
+centrosomes	O
+does	O
+not	O
+occur	O
+in	O
+embryos	O
+depleted	O
+for	O
+DHC	O
+-	O
+1	O
+with	O
+RNAi	O
+(	O
+our	O
+unpublished	O
+results	O
+)	O
+,	O
+indicating	O
+that	O
+these	O
+proteins	O
+require	O
+the	O
+mutant	O
+DHC	O
+-	O
+1	O
+polypeptide	O
+for	O
+centrosomal	O
+targeting	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+embryos	O
+.	O
+
+In	O
+summary	O
+,	O
+the	O
+DYRB	O
+-	O
+1	O
+and	O
+DYLT	O
+-	O
+1	O
+proteins	O
+localize	O
+to	O
+sites	O
+where	O
+the	O
+DHC	O
+-	O
+1	O
+HC	O
+is	O
+also	O
+found	O
+in	O
+wild	O
+-	O
+type	O
+embryos	O
+,	O
+and	O
+all	O
+three	O
+proteins	O
+respond	O
+similarly	O
+to	O
+mutational	O
+alterations	O
+in	O
+DHC	O
+-	O
+1	O
+.	O
+
+Genetic	O
+Characterization	O
+of	O
+the	O
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+Dynein	O
+Light	O
+Chains	O
+
+We	O
+obtained	O
+putative	O
+null	O
+alleles	O
+to	O
+determine	O
+if	O
+dylt	O
+-	O
+1	O
+and	O
+dyrb	O
+-	O
+1	O
+function	O
+in	O
+dynein	O
+-	O
+dependent	O
+processes	O
+.	O
+
+DYLT	O
+-	O
+1	O
+is	O
+40	O
+%	O
+identical	O
+to	O
+human	B
+DYNLT3	O
+and	O
+38	O
+%	O
+identical	O
+to	O
+Drosophila	B
+Dlc90F	O
+(	O
+see	O
+alignment	O
+in	O
+Figure	O
+8A	O
+)	O
+.	O
+
+Two	O
+other	O
+C	B
+.	I
+elegans	I
+genes	O
+,	O
+dylt	O
+-	O
+2	O
+and	O
+dylt	O
+-	O
+3	O
+,	O
+encode	O
+more	O
+divergent	O
+members	O
+of	O
+this	O
+protein	O
+family	O
+.	O
+
+DYRB	O
+-	O
+1	O
+is	O
+49	O
+%	O
+identical	O
+to	O
+both	O
+human	B
+DYNLRB1	O
+and	O
+Drosophila	B
+Robl	O
+(	O
+see	O
+alignment	O
+in	O
+Figure	O
+8A	O
+)	O
+.	O
+
+There	O
+do	O
+not	O
+appear	O
+to	O
+be	O
+other	O
+Roadblock	O
+genes	O
+in	O
+the	O
+C	B
+.	I
+elegans	I
+genome	O
+[	O
+3	O
+]	O
+.	O
+
+Deletion	O
+alleles	O
+for	O
+both	O
+dylt	O
+-	O
+1	O
+and	O
+dyrb	O
+-	O
+1	O
+have	O
+been	O
+isolated	O
+(	O
+Figure	O
+8B	O
+)	O
+.	O
+
+The	O
+dylt	O
+-	O
+1	O
+(	O
+ok417	O
+)	O
+deletion	O
+removes	O
+the	O
+entire	O
+DYLT	O
+-	O
+1	O
+open	O
+reading	O
+frame	O
+and	O
+does	O
+not	O
+affect	O
+adjacent	O
+coding	O
+regions	O
+.	O
+
+The	O
+dyrb	O
+-	O
+1	O
+(	O
+tm2645	O
+)	O
+deletion	O
+removes	O
+69	O
+%	O
+of	O
+the	O
+dyrb	O
+-	O
+1	O
+coding	O
+region	O
+,	O
+leaving	O
+29	O
+predicted	O
+N	O
+-	O
+terminal	O
+amino	O
+acids	O
+,	O
+and	O
+does	O
+not	O
+affect	O
+adjacent	O
+coding	O
+regions	O
+.	O
+
+Both	O
+deletions	O
+are	O
+currently	O
+annotated	O
+as	O
+homozygous	O
+viable	O
+[	O
+29	O
+]	O
+.	O
+
+However	O
+,	O
+we	O
+found	O
+that	O
+the	O
+dyrb	O
+-	O
+1	O
+(	O
+tm2645	O
+)	O
+strain	O
+was	O
+in	O
+fact	O
+heterozygous	O
+for	O
+the	O
+deletion	O
+and	O
+that	O
+most	O
+embryos	O
+produced	O
+by	O
+dyrb	O
+-	O
+1	O
+(	O
+tm2645	O
+)	O
+homozygous	O
+animals	O
+failed	O
+to	O
+hatch	O
+(	O
+Figure	O
+8C	O
+)	O
+.	O
+
+Homozygous	O
+dyrb	O
+-	O
+1	O
+(	O
+tm2645	O
+)	O
+worms	B
+also	O
+showed	O
+an	O
+egg	O
+-	O
+laying	O
+defect	O
+and	O
+produced	O
+small	O
+broods	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+To	O
+determine	O
+if	O
+the	O
+dyrb	O
+-	O
+1	O
+deletion	O
+was	O
+responsible	O
+for	O
+the	O
+embryonic	O
+lethality	O
+,	O
+we	O
+crossed	O
+the	O
+GFP	O
+:	O
+:	O
+dyrb	O
+-	O
+1	O
+transgene	O
+into	O
+the	O
+deletion	O
+background	O
+.	O
+
+The	O
+presence	O
+of	O
+the	O
+transgene	O
+fully	O
+rescued	O
+the	O
+embryonic	O
+lethality	O
+(	O
+Figure	O
+8C	O
+)	O
+,	O
+but	O
+not	O
+the	O
+egg	O
+-	O
+laying	O
+defect	O
+:	O
+the	O
+transgene	O
+is	O
+driven	O
+from	O
+a	O
+germline	O
+-	O
+specific	O
+promoter	O
+and	O
+so	O
+would	O
+not	O
+be	O
+expected	O
+to	O
+rescue	O
+zygotic	O
+phenotypes	O
+.	O
+
+The	O
+embryonic	O
+lethality	O
+exhibited	O
+by	O
+dyrb	O
+-	O
+1	O
+(	O
+tm2645	O
+)	O
+mutants	O
+is	O
+consistent	O
+with	O
+RNAi	O
+studies	O
+performed	O
+by	O
+injection	O
+or	O
+soaking	O
+[	O
+12	O
+,	O
+38	O
+]	O
+.	O
+
+In	O
+contrast	O
+,	O
+homozygous	O
+dylt	O
+-	O
+1	O
+deletion	O
+mutants	O
+did	O
+not	O
+exhibit	O
+any	O
+larval	O
+or	O
+embryonic	O
+lethality	O
+(	O
+Figure	O
+8C	O
+)	O
+.	O
+
+To	O
+determine	O
+if	O
+these	O
+dynein	O
+light	O
+chain	O
+mutants	O
+exhibit	O
+dynein	O
+HC	O
+-	O
+like	O
+phenotypes	O
+,	O
+we	O
+observed	O
+the	O
+completion	O
+of	O
+meiotic	O
+polar	O
+body	O
+extrusion	O
+and	O
+the	O
+first	O
+two	O
+mitotic	O
+cell	O
+divisions	O
+in	O
+mutant	O
+embryos	O
+(	O
+Figure	O
+8D	O
+)	O
+.	O
+
+The	O
+dylt	O
+-	O
+1	O
+embryos	O
+appeared	O
+wild	O
+type	O
+for	O
+completion	O
+of	O
+meiosis	O
+,	O
+pronuclear	O
+migration	O
+,	O
+and	O
+spindle	O
+assembly	O
+and	O
+function	O
+.	O
+
+However	O
+,	O
+the	O
+dyrb	O
+-	O
+1	O
+embryos	O
+occasionally	O
+contained	O
+extra	O
+female	O
+pronuclei	O
+(	O
+observed	O
+in	O
+four	O
+of	O
+12	O
+recordings	O
+,	O
+Figure	O
+8D	O
+)	O
+,	O
+suggesting	O
+that	O
+polar	O
+body	O
+extrusion	O
+was	O
+defective	O
+,	O
+and	O
+pronuclear	O
+migration	O
+was	O
+often	O
+slow	O
+compared	O
+to	O
+wild	O
+-	O
+type	O
+embryos	O
+.	O
+
+Once	O
+formed	O
+,	O
+spindles	O
+appeared	O
+functional	O
+using	O
+Nomarski	O
+optics	O
+,	O
+although	O
+they	O
+were	O
+frequently	O
+positioned	O
+improperly	O
+and	O
+had	O
+large	O
+spindle	O
+poles	O
+,	O
+as	O
+has	O
+also	O
+been	O
+observed	O
+after	O
+RNAi	O
+knockdown	O
+[	O
+12	O
+]	O
+.	O
+
+Thus	O
+,	O
+these	O
+two	O
+genes	O
+are	O
+not	O
+strictly	O
+essential	O
+,	O
+but	O
+the	O
+DYRB	O
+-	O
+1	O
+protein	O
+clearly	O
+is	O
+required	O
+for	O
+dynein	O
+-	O
+dependent	O
+processes	O
+.	O
+
+Discussion	O
+
+By	O
+using	O
+the	O
+suppressor	O
+screening	O
+method	O
+outlined	O
+in	O
+Figure	O
+2B	O
+,	O
+we	O
+have	O
+isolated	O
+and	O
+characterized	O
+49	O
+genes	O
+that	O
+when	O
+reduced	O
+in	O
+function	O
+can	O
+suppress	O
+a	O
+partial	O
+loss	O
+of	O
+dynein	O
+HC	O
+function	O
+.	O
+
+This	O
+screening	O
+procedure	O
+takes	O
+advantage	O
+of	O
+sensitized	O
+genetic	O
+backgrounds	O
+using	O
+conditional	O
+mutants	O
+,	O
+can	O
+be	O
+completed	O
+for	O
+one	O
+mutant	O
+in	O
+less	O
+than	O
+5	O
+wk	O
+,	O
+and	O
+is	O
+scalable	O
+so	O
+that	O
+many	O
+mutants	O
+can	O
+be	O
+screened	O
+in	O
+parallel	O
+.	O
+
+In	O
+fact	O
+,	O
+we	O
+have	O
+performed	O
+15	O
+such	O
+screens	O
+in	O
+different	O
+sensitized	O
+backgrounds	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+By	O
+using	O
+three	O
+dhc	O
+-	O
+1ts	O
+mutant	O
+strains	O
+,	O
+we	O
+found	O
+that	O
+strain	O
+background	O
+differences	O
+and	O
+allele	O
+specificity	O
+are	O
+minimal	O
+because	O
+most	O
+of	O
+these	O
+genes	O
+suppress	O
+all	O
+three	O
+dynein	O
+mutants	O
+when	O
+reduced	O
+in	O
+function	O
+using	O
+RNAi	O
+.	O
+
+Furthermore	O
+,	O
+by	O
+using	O
+two	O
+unrelated	O
+ts	O
+mutants	O
+to	O
+assay	O
+for	O
+specificity	O
+,	O
+we	O
+found	O
+that	O
+57	O
+%	O
+of	O
+the	O
+suppressor	O
+genes	O
+suppress	O
+multiple	O
+unrelated	O
+mutant	O
+loci	O
+.	O
+
+Thus	O
+,	O
+it	O
+is	O
+clear	O
+that	O
+assaying	O
+the	O
+specificity	O
+of	O
+suppression	O
+is	O
+critical	O
+for	O
+evaluating	O
+the	O
+functional	O
+significance	O
+of	O
+these	O
+RNAi	O
+interactions	O
+.	O
+
+Eliminating	O
+the	O
+analysis	O
+of	O
+these	O
+nonspecific	O
+genes	O
+in	O
+future	O
+screens	O
+will	O
+save	O
+time	O
+and	O
+resources	O
+.	O
+
+Most	O
+of	O
+the	O
+specific	O
+suppressor	O
+proteins	O
+we	O
+examined	O
+appear	O
+to	O
+overlap	O
+in	O
+subcellular	O
+localization	O
+with	O
+the	O
+dynein	O
+HC	O
+,	O
+based	O
+on	O
+previous	O
+studies	O
+of	O
+DHC	O
+-	O
+1	O
+,	O
+while	O
+one	O
+nonspecific	O
+suppressor	O
+protein	O
+,	O
+STAR	O
+-	O
+2	O
+,	O
+localized	O
+to	O
+germline	O
+P	O
+-	O
+granules	O
+,	O
+where	O
+dynein	O
+is	O
+not	O
+known	O
+to	O
+function	O
+.	O
+
+Many	O
+of	O
+the	O
+20	O
+genes	O
+that	O
+specifically	O
+suppress	O
+multiple	O
+dhc	O
+-	O
+1ts	O
+alleles	O
+are	O
+nonessential	O
+in	O
+C	B
+.	I
+elegans	I
+but	O
+well	O
+conserved	O
+nonetheless	O
+.	O
+
+Six	O
+of	O
+eight	O
+deletion	O
+alleles	O
+available	O
+for	O
+the	O
+20	O
+specific	O
+suppressor	O
+genes	O
+are	O
+homozygous	O
+viable	O
+,	O
+and	O
+six	O
+additional	O
+specific	O
+genes	O
+do	O
+not	O
+display	O
+lethal	O
+phenotypes	O
+when	O
+reduced	O
+in	O
+function	O
+by	O
+RNAi	O
+in	O
+wild	O
+-	O
+type	O
+worms	B
+[	O
+29	O
+]	O
+.	O
+
+Thus	O
+,	O
+our	O
+genetic	O
+screening	O
+has	O
+identified	O
+roles	O
+in	O
+an	O
+essential	O
+process	O
+for	O
+at	O
+least	O
+12	O
+apparently	O
+nonessential	O
+genes	O
+.	O
+
+Fourteen	O
+of	O
+the	O
+specific	O
+dynein	O
+suppressor	O
+genes	O
+have	O
+human	B
+orthologs	O
+as	O
+determined	O
+by	O
+best	O
+reciprocal	O
+BLAST	O
+hits	O
+(	O
+Table	O
+1	O
+)	O
+,	O
+while	O
+mop	O
+-	O
+25	O
+.	O
+2	O
+has	O
+a	O
+conserved	O
+human	B
+homolog	O
+but	O
+also	O
+a	O
+paralog	O
+in	O
+C	B
+.	I
+elegans	I
+.	O
+
+Eleven	O
+of	O
+these	O
+conserved	O
+genes	O
+are	O
+nonessential	O
+in	O
+C	B
+.	I
+elegans	I
+.	O
+
+Interestingly	O
+,	O
+eight	O
+of	O
+the	O
+conserved	O
+genes	O
+in	O
+Table	O
+1	O
+have	O
+been	O
+implicated	O
+in	O
+human	B
+disease	O
+etiology	O
+,	O
+with	O
+three	O
+of	O
+them	O
+identified	O
+as	O
+the	O
+causative	O
+gene	O
+[	O
+39	O
+-	O
+41	O
+]	O
+.	O
+
+Thus	O
+,	O
+using	O
+sensitized	O
+genetic	O
+backgrounds	O
+for	O
+genome	O
+-	O
+wide	O
+modifier	O
+screens	O
+can	O
+identify	O
+roles	O
+for	O
+nonessential	O
+but	O
+conserved	O
+genes	O
+and	O
+thereby	O
+provide	O
+insights	O
+into	O
+human	B
+disease	O
+.	O
+
+Nonspecific	O
+Suppression	O
+of	O
+Conditional	O
+Mutants	O
+
+We	O
+examined	O
+the	O
+predicted	O
+molecular	O
+functions	O
+of	O
+the	O
+suppressor	O
+proteins	O
+to	O
+better	O
+understand	O
+the	O
+basis	O
+for	O
+the	O
+nonspecific	O
+suppression	O
+phenomenon	O
+.	O
+
+Strikingly	O
+,	O
+many	O
+of	O
+the	O
+nonspecific	O
+suppressor	O
+genes	O
+encode	O
+proteins	O
+with	O
+predicted	O
+roles	O
+in	O
+mitochondrial	O
+,	O
+ribosomal	O
+,	O
+and	O
+collagen	O
+function	O
+(	O
+18	O
+of	O
+29	O
+genes	O
+,	O
+or	O
+62	O
+%	O
+)	O
+,	O
+while	O
+only	O
+two	O
+such	O
+genes	O
+appeared	O
+to	O
+specifically	O
+suppress	O
+dhc	O
+-	O
+1	O
+(	O
+2	O
+of	O
+20	O
+genes	O
+or	O
+10	O
+%	O
+)	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+stress	O
+produced	O
+by	O
+RNAi	O
+knockdown	O
+of	O
+these	O
+suppressor	O
+genes	O
+triggers	O
+the	O
+activity	O
+of	O
+molecular	O
+chaperones	O
+that	O
+can	O
+generally	O
+restore	O
+function	O
+to	O
+ts	O
+proteins	O
+.	O
+
+Indeed	O
+,	O
+mutation	O
+of	O
+dpy	O
+-	O
+10	O
+is	O
+known	O
+to	O
+suppress	O
+three	O
+other	O
+ts	O
+mutants	O
+:	O
+glp	O
+-	O
+1	O
+,	O
+emb	O
+-	O
+5	O
+,	O
+and	O
+mup	O
+-	O
+1	O
+[	O
+42	O
+-	O
+44	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+RNAi	O
+reduction	O
+of	O
+dpy	O
+-	O
+10	O
+,	O
+star	O
+-	O
+2	O
+,	O
+osr	O
+-	O
+1	O
+,	O
+or	O
+C50D2	O
+.	O
+1	O
+(	O
+all	O
+suppressors	O
+of	O
+dhc	O
+-	O
+1	O
+,	O
+lit	O
+-	O
+1	O
+,	O
+and	O
+spn	O
+-	O
+4	O
+ts	O
+alleles	O
+)	O
+induces	O
+the	O
+glycerol	O
+biosynthetic	O
+gene	O
+gpdh	O
+-	O
+2	O
+,	O
+while	O
+dpy	O
+-	O
+10	O
+and	O
+osr	O
+-	O
+1	O
+mutants	O
+exhibit	O
+increased	O
+glycerol	O
+levels	O
+,	O
+a	O
+condition	O
+that	O
+promotes	O
+protein	O
+stability	O
+[	O
+45	O
+]	O
+.	O
+
+We	O
+suggest	O
+that	O
+partial	O
+loss	O
+of	O
+central	O
+metabolic	O
+processes	O
+can	O
+invoke	O
+stress	O
+responses	O
+that	O
+nonspecifically	O
+alleviate	O
+protein	O
+-	O
+folding	O
+problems	O
+in	O
+ts	O
+proteins	O
+.	O
+
+Filtering	O
+out	O
+these	O
+nonspecific	O
+interactions	O
+by	O
+testing	O
+unrelated	O
+conditional	O
+mutants	O
+increases	O
+the	O
+likelihood	O
+that	O
+the	O
+remaining	O
+suppressor	O
+genes	O
+are	O
+more	O
+directly	O
+involved	O
+with	O
+dynein	O
+function	O
+.	O
+
+However	O
+,	O
+ts	O
+mutants	O
+likely	O
+differ	O
+in	O
+their	O
+susceptibility	O
+to	O
+nonspecific	O
+suppression	O
+mechanisms	O
+,	O
+and	O
+some	O
+apparently	O
+unrelated	O
+ts	O
+mutants	O
+might	O
+share	O
+common	O
+cofactors	O
+such	O
+that	O
+both	O
+mutants	O
+are	O
+suppressed	O
+by	O
+depletion	O
+of	O
+the	O
+same	O
+cofactor	O
+.	O
+
+Nevertheless	O
+,	O
+we	O
+expect	O
+that	O
+more	O
+extensive	O
+testing	O
+for	O
+specificity	O
+will	O
+prove	O
+very	O
+useful	O
+for	O
+judging	O
+the	O
+significance	O
+of	O
+modifier	O
+interactions	O
+.	O
+
+Possible	O
+Relevance	O
+of	O
+Suppressor	O
+Proteins	O
+to	O
+Dynein	O
+Function	O
+
+We	O
+examined	O
+the	O
+localization	O
+of	O
+a	O
+number	O
+of	O
+GFP	O
+fusions	O
+to	O
+suppressor	O
+proteins	O
+to	O
+gain	O
+insight	O
+into	O
+their	O
+functional	O
+relationship	O
+to	O
+dynein	O
+.	O
+
+In	O
+several	O
+cases	O
+,	O
+the	O
+subcellular	O
+distribution	O
+of	O
+the	O
+suppressor	O
+proteins	O
+overlapped	O
+in	O
+different	O
+ways	O
+with	O
+the	O
+known	O
+and	O
+nearly	O
+ubiquitous	O
+distribution	O
+of	O
+cytoplasmic	O
+dynein	O
+in	O
+the	O
+early	O
+C	B
+.	I
+elegans	I
+embryo	O
+.	O
+
+In	O
+fact	O
+,	O
+the	O
+only	O
+specific	O
+suppressor	O
+that	O
+did	O
+not	O
+display	O
+dynein	O
+-	O
+like	O
+localization	O
+was	O
+F10E7	O
+.	O
+8	O
+,	O
+a	O
+homolog	O
+of	O
+yeast	B
+Far11	O
+of	O
+unknown	O
+function	O
+[	O
+46	O
+]	O
+,	O
+which	O
+was	O
+nuclear	O
+.	O
+
+The	O
+one	O
+nonspecific	O
+suppressor	O
+protein	O
+we	O
+examined	O
+did	O
+not	O
+show	O
+any	O
+dynein	O
+-	O
+like	O
+localization	O
+patterns	O
+.	O
+
+The	O
+subcellular	O
+localizations	O
+of	O
+the	O
+GFP	O
+:	O
+:	O
+suppressor	O
+protein	O
+fusions	O
+are	O
+intriguing	O
+.	O
+
+However	O
+,	O
+given	O
+the	O
+nearly	O
+ubiquitous	O
+distribution	O
+of	O
+dynein	O
+in	O
+early	O
+embryonic	O
+cells	O
+,	O
+biochemical	O
+tests	O
+for	O
+direct	O
+association	O
+are	O
+needed	O
+to	O
+address	O
+the	O
+significance	O
+of	O
+any	O
+colocalization	O
+detected	O
+using	O
+light	O
+microscopy	O
+.	O
+
+We	O
+are	O
+particularly	O
+interested	O
+in	O
+suppressor	O
+proteins	O
+that	O
+localize	O
+to	O
+mitotic	O
+spindle	O
+poles	O
+:	O
+the	O
+association	O
+of	O
+the	O
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+predicted	O
+dynein	O
+light	O
+chains	O
+with	O
+centrosomes	O
+and	O
+spindle	O
+poles	O
+suggests	O
+that	O
+they	O
+may	O
+be	O
+components	O
+of	O
+cytoplasmic	O
+dynein	O
+in	O
+C	B
+.	I
+elegans	I
+.	O
+
+Localization	O
+of	O
+cytoplasmic	O
+dynein	O
+to	O
+centrosomes	O
+and	O
+spindle	O
+poles	O
+is	O
+well	O
+established	O
+[	O
+47	O
+,	O
+48	O
+]	O
+,	O
+and	O
+the	O
+inhibition	O
+of	O
+dynein	O
+function	O
+prevents	O
+centrosome	O
+separation	O
+,	O
+centrosome	O
+attachment	O
+to	O
+nuclei	O
+,	O
+and	O
+the	O
+formation	O
+of	O
+bipolar	O
+spindles	O
+[	O
+6	O
+,	O
+10	O
+,	O
+49	O
+,	O
+50	O
+]	O
+.	O
+
+Moreover	O
+,	O
+the	O
+centrosomal	O
+localization	O
+of	O
+DHC	O
+-	O
+1	O
+,	O
+DYLT	O
+-	O
+1	O
+,	O
+and	O
+DYRB	O
+-	O
+1	O
+are	O
+all	O
+greatly	O
+enhanced	O
+in	O
+dhc	O
+-	O
+1ts	O
+mutant	O
+embryos	O
+:	O
+this	O
+dependence	O
+of	O
+the	O
+light	O
+chain	O
+distribution	O
+on	O
+the	O
+HC	O
+further	O
+suggests	O
+they	O
+reside	O
+in	O
+the	O
+same	O
+motor	O
+complex	O
+(	O
+Figure	O
+7	O
+and	O
+[	O
+10	O
+]	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+roadblock	O
+light	O
+chains	O
+are	O
+well	O
+-	O
+established	O
+components	O
+of	O
+dynein	O
+,	O
+and	O
+all	O
+of	O
+the	O
+roadblock	O
+protein	O
+in	O
+mammalian	O
+liver	O
+extracts	O
+is	O
+dynein	O
+associated	O
+[	O
+51	O
+,	O
+52	O
+]	O
+.	O
+
+Finally	O
+,	O
+a	O
+DYLT	O
+-	O
+1	O
+homolog	O
+in	O
+vertebrates	O
+is	O
+a	O
+stoichiometric	O
+subunit	O
+of	O
+cytoplasmic	O
+dynein	O
+[	O
+53	O
+]	O
+.	O
+
+The	O
+presence	O
+of	O
+these	O
+two	O
+light	O
+chains	O
+in	O
+a	O
+dynein	O
+complex	O
+is	O
+consistent	O
+with	O
+them	O
+having	O
+either	O
+positive	O
+or	O
+negative	O
+roles	O
+in	O
+the	O
+regulation	O
+of	O
+HC	O
+function	O
+(	O
+see	O
+below	O
+)	O
+.	O
+
+Cytoplasmic	O
+dynein	O
+is	O
+found	O
+on	O
+the	O
+nuclear	O
+envelope	O
+where	O
+it	O
+is	O
+thought	O
+to	O
+regulate	O
+nuclear	O
+membrane	O
+breakdown	O
+during	O
+mitosis	O
+[	O
+54	O
+]	O
+,	O
+and	O
+dynein	O
+plays	O
+roles	O
+during	O
+the	O
+trafficking	O
+of	O
+endoplasmic	O
+reticulum	O
+components	O
+[	O
+55	O
+,	O
+56	O
+]	O
+.	O
+
+Therefore	O
+,	O
+the	O
+nuclear	O
+envelope	O
+/	O
+endoplasmic	O
+reticulum	O
+proteins	O
+NPP	O
+-	O
+22	O
+and	O
+K04F10	O
+.	O
+3	O
+could	O
+couple	O
+dynein	O
+activity	O
+to	O
+either	O
+of	O
+these	O
+structures	O
+.	O
+
+The	O
+anc	O
+-	O
+1	O
+gene	O
+was	O
+also	O
+isolated	O
+in	O
+our	O
+screening	O
+and	O
+ANC	O
+-	O
+1	O
+is	O
+localized	O
+to	O
+the	O
+nuclear	O
+envelope	O
+where	O
+it	O
+maintains	O
+nuclear	O
+positioning	O
+in	O
+postembryonic	O
+cells	O
+[	O
+57	O
+]	O
+.	O
+
+Reducing	O
+the	O
+function	O
+of	O
+these	O
+three	O
+genes	O
+may	O
+suppress	O
+partial	O
+loss	O
+of	O
+dynein	O
+HC	O
+mutants	O
+by	O
+reducing	O
+the	O
+need	O
+for	O
+dynein	O
+during	O
+nuclear	O
+envelope	O
+breakdown	O
+,	O
+through	O
+constitutive	O
+partial	O
+destabilization	O
+of	O
+the	O
+nuclear	O
+envelope	O
+.	O
+
+The	O
+distribution	O
+of	O
+the	O
+cytoplasmic	O
+dynein	O
+HC	O
+includes	O
+sites	O
+other	O
+than	O
+spindle	O
+poles	O
+and	O
+nuclear	O
+envelopes	O
+in	O
+C	B
+.	I
+elegans	I
+,	O
+for	O
+example	O
+,	O
+at	O
+the	O
+cell	O
+cortex	O
+and	O
+at	O
+the	O
+cell	O
+division	O
+remnant	O
+called	O
+the	O
+midbody	O
+[	O
+6	O
+,	O
+10	O
+]	O
+.	O
+
+The	O
+MOP	O
+-	O
+25	O
+.	O
+2	O
+protein	O
+was	O
+found	O
+at	O
+the	O
+midbody	O
+and	O
+faintly	O
+at	O
+spindle	O
+poles	O
+.	O
+
+The	O
+MOP	O
+-	O
+25	O
+.	O
+2	O
+ortholog	O
+in	O
+S	B
+.	I
+pombe	I
+,	O
+Pmo25	O
+,	O
+is	O
+also	O
+present	O
+at	O
+the	O
+cell	O
+division	O
+site	O
+and	O
+on	O
+spindle	O
+poles	O
+[	O
+58	O
+]	O
+.	O
+
+Mammalian	O
+MOP	O
+-	O
+25	O
+.	O
+2	O
+homologs	O
+stimulate	O
+the	O
+kinase	O
+activity	O
+of	O
+the	O
+LKB1	O
+tumor	O
+suppressor	O
+(	O
+the	O
+C	B
+.	I
+elegans	I
+ortholog	O
+is	O
+PAR	O
+-	O
+4	O
+)	O
+,	O
+which	O
+in	O
+turn	O
+activates	O
+MARK	O
+microtubule	O
+-	O
+destabilizing	O
+kinases	O
+[	O
+59	O
+,	O
+60	O
+]	O
+.	O
+
+The	O
+C	B
+.	I
+elegans	I
+MARK	O
+ortholog	O
+,	O
+PAR	O
+-	O
+1	O
+,	O
+controls	O
+cell	O
+polarity	O
+during	O
+embryogenesis	O
+,	O
+and	O
+orthologs	O
+have	O
+been	O
+implicated	O
+in	O
+regulation	O
+of	O
+microtubule	O
+dynamics	O
+from	O
+yeast	B
+to	O
+humans	B
+[	O
+61	O
+-	O
+64	O
+]	O
+.	O
+
+Lastly	O
+,	O
+the	O
+two	O
+splice	O
+isoforms	O
+of	O
+EFA	O
+-	O
+6	O
+were	O
+associated	O
+with	O
+the	O
+anterior	O
+cell	O
+cortex	O
+in	O
+late	O
+one	O
+-	O
+cell	O
+embryos	O
+.	O
+
+Cortically	O
+localized	O
+dynein	O
+may	O
+have	O
+important	O
+roles	O
+in	O
+applying	O
+forces	O
+to	O
+astral	O
+microtubules	O
+that	O
+influence	O
+mitotic	O
+spindle	O
+positioning	O
+and	O
+chromosome	O
+separation	O
+during	O
+anaphase	O
+[	O
+10	O
+,	O
+65	O
+,	O
+66	O
+]	O
+.	O
+
+EFA6	O
+ARF	O
+guanine	O
+nucleotide	O
+exchange	O
+factors	O
+require	O
+their	O
+pleckstrin	O
+homology	O
+domain	O
+for	O
+cortical	O
+targeting	O
+,	O
+and	O
+are	O
+known	O
+to	O
+regulate	O
+cortical	O
+actin	O
+dynamics	O
+in	O
+vertebrate	O
+cells	O
+by	O
+promoting	O
+guanine	O
+nucleotide	O
+exchange	O
+on	O
+ARF6	O
+[	O
+67	O
+,	O
+68	O
+]	O
+.	O
+
+Our	O
+results	O
+identifying	O
+efa	O
+-	O
+6	O
+as	O
+a	O
+dynein	O
+HC	O
+suppressor	O
+suggest	O
+a	O
+functional	O
+linkage	O
+of	O
+the	O
+actin	O
+and	O
+microtubule	O
+cytoskeletons	O
+at	O
+the	O
+cell	O
+cortex	O
+.	O
+
+Interestingly	O
+,	O
+two	O
+yeast	B
+pleckstrin	O
+homology	O
+domain	O
+proteins	O
+,	O
+Num1	O
+and	O
+mcp5	O
++	O
+,	O
+localize	O
+to	O
+the	O
+cell	O
+cortex	O
+and	O
+direct	O
+astral	O
+microtubule	O
+and	O
+dynein	O
+function	O
+,	O
+although	O
+they	O
+do	O
+not	O
+contain	O
+a	O
+Sec7	O
+domain	O
+like	O
+EFA	O
+-	O
+6	O
+does	O
+[	O
+69	O
+-	O
+71	O
+]	O
+.	O
+
+Function	O
+of	O
+Dynein	O
+Intermediate	O
+,	O
+Light	O
+Intermediate	O
+,	O
+and	O
+Light	O
+Chains	O
+
+The	O
+dynein	O
+chains	O
+in	O
+C	B
+.	I
+elegans	I
+exhibit	O
+strikingly	O
+different	O
+functional	O
+requirements	O
+.	O
+
+The	O
+DYRB	O
+-	O
+1	O
+roadblock	O
+light	O
+chain	O
+is	O
+required	O
+for	O
+completion	O
+of	O
+meiosis	O
+and	O
+pronuclear	O
+migration	O
+,	O
+but	O
+an	O
+at	O
+least	O
+partially	O
+functional	O
+mitotic	O
+spindle	O
+forms	O
+in	O
+the	O
+absence	O
+of	O
+DYRB	O
+-	O
+1	O
+(	O
+Figure	O
+8	O
+)	O
+.	O
+
+The	O
+DLI	O
+-	O
+1	O
+light	O
+intermediate	O
+chain	O
+is	O
+required	O
+for	O
+multiple	O
+dynein	O
+-	O
+dependent	O
+functions	O
+:	O
+pronuclear	O
+migration	O
+,	O
+centrosome	O
+separation	O
+,	O
+and	O
+meiotic	O
+and	O
+mitotic	O
+spindle	O
+function	O
+[	O
+12	O
+,	O
+34	O
+]	O
+.	O
+
+DLI	O
+-	O
+1	O
+may	O
+promote	O
+nuclear	O
+envelope	O
+targeting	O
+of	O
+both	O
+centrosomes	O
+and	O
+DHC	O
+-	O
+1	O
+by	O
+interacting	O
+with	O
+the	O
+nuclear	O
+envelope	O
+protein	O
+ZYG	O
+-	O
+12	O
+[	O
+35	O
+]	O
+.	O
+
+The	O
+second	O
+worm	O
+light	O
+intermediate	O
+chain	O
+gene	O
+,	O
+xbx	O
+-	O
+1	O
+,	O
+is	O
+required	O
+for	O
+cilia	O
+function	O
+but	O
+not	O
+early	O
+embryonic	O
+development	O
+[	O
+12	O
+,	O
+72	O
+]	O
+.	O
+
+RNAi	O
+knockdown	O
+of	O
+DLC	O
+-	O
+1	O
+,	O
+one	O
+of	O
+three	O
+LC8	O
+proteins	O
+in	O
+C	B
+.	I
+elegans	I
+,	O
+produces	O
+defects	O
+similar	O
+to	O
+dli	O
+-	O
+1	O
+but	O
+knockdown	O
+of	O
+the	O
+other	O
+two	O
+LC8	O
+-	O
+related	O
+genes	O
+does	O
+not	O
+result	O
+in	O
+any	O
+phenotypes	O
+[	O
+12	O
+]	O
+.	O
+
+RNAi	O
+depletion	O
+of	O
+dyci	O
+-	O
+1	O
+results	O
+in	O
+severe	O
+meiotic	O
+,	O
+pronuclear	O
+migration	O
+,	O
+and	O
+mitotic	O
+spindle	O
+assembly	O
+defects	O
+[	O
+12	O
+]	O
+and	O
+in	O
+our	O
+feeding	O
+RNAi	O
+regimen	O
+dyci	O
+-	O
+1	O
+(	O
+RNAi	O
+)	O
+produces	O
+a	O
+larval	O
+arrest	O
+phenotype	O
+similar	O
+to	O
+that	O
+observed	O
+for	O
+dhc	O
+-	O
+1	O
+.	O
+
+Finally	O
+,	O
+the	O
+three	O
+Tctex1	O
+proteins	O
+in	O
+C	B
+.	I
+elegans	I
+,	O
+DYLT	O
+-	O
+1	O
+,	O
+2	O
+,	O
+and	O
+3	O
+,	O
+are	O
+not	O
+essential	O
+for	O
+dynein	O
+-	O
+related	O
+functions	O
+[	O
+12	O
+]	O
+.	O
+
+As	O
+the	O
+dyrb	O
+-	O
+1	O
+,	O
+dlc	O
+-	O
+1	O
+,	O
+and	O
+dli	O
+-	O
+1	O
+dynein	O
+AC	O
+genes	O
+display	O
+some	O
+dhc	O
+-	O
+1	O
+-	O
+like	O
+requirements	O
+,	O
+they	O
+positively	O
+influence	O
+dynein	O
+function	O
+.	O
+
+However	O
+,	O
+because	O
+reducing	O
+their	O
+function	O
+suppresses	O
+dhc	O
+-	O
+1ts	O
+mutants	O
+,	O
+they	O
+may	O
+also	O
+exert	O
+negative	O
+regulation	O
+(	O
+along	O
+with	O
+dylt	O
+-	O
+1	O
+)	O
+on	O
+the	O
+heavy	O
+chain	O
+.	O
+
+Negative	O
+Regulation	O
+of	O
+Dynein	O
+HC	O
+by	O
+Light	O
+Chain	O
+Subunits	O
+
+Finding	O
+that	O
+reducing	O
+the	O
+function	O
+of	O
+light	O
+and	O
+light	O
+intermediate	O
+dynein	O
+chains	O
+suppressed	O
+the	O
+partial	O
+loss	O
+of	O
+HC	O
+function	O
+was	O
+a	O
+striking	O
+result	O
+.	O
+
+One	O
+member	O
+of	O
+each	O
+of	O
+four	O
+subunit	O
+classes	O
+can	O
+suppress	O
+the	O
+embryonic	O
+lethality	O
+associated	O
+with	O
+three	O
+dhc	O
+-	O
+1	O
+ts	O
+mutants	O
+(	O
+Figure	O
+5	O
+)	O
+.	O
+
+We	O
+have	O
+considered	O
+two	O
+different	O
+models	O
+to	O
+explain	O
+how	O
+RNAi	O
+-	O
+mediated	O
+depletion	O
+of	O
+these	O
+dynein	O
+ACs	O
+can	O
+suppress	O
+reduced	O
+HC	O
+function	O
+.	O
+
+First	O
+,	O
+these	O
+dynein	O
+subunits	O
+could	O
+be	O
+in	O
+functional	O
+complexes	O
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+,	O
+and	O
+exert	O
+negative	O
+regulation	O
+on	O
+,	O
+the	O
+DHC	O
+-	O
+1	O
+HC	O
+(	O
+Figure	O
+5B	O
+)	O
+.	O
+
+The	O
+suppression	O
+mechanism	O
+in	O
+this	O
+case	O
+proposes	O
+that	O
+removal	O
+of	O
+the	O
+suppressing	O
+ACs	O
+increases	O
+residual	O
+mutant	O
+DHC	O
+-	O
+1	O
+activity	O
+.	O
+
+The	O
+other	O
+,	O
+nonsuppressing	O
+,	O
+accessory	O
+subunits	O
+might	O
+then	O
+function	O
+in	O
+nonmitotic	O
+cellular	O
+processes	O
+such	O
+as	O
+neuronal	O
+transport	O
+or	O
+organelle	O
+positioning	O
+.	O
+
+In	O
+support	O
+of	O
+this	O
+view	O
+,	O
+physical	O
+removal	O
+of	O
+the	O
+intermediate	O
+chains	O
+of	O
+rat	B
+cytoplasmic	O
+dynein	O
+increased	O
+HC	O
+ATPase	O
+activity	O
+by	O
+about	O
+4	O
+-	O
+fold	O
+(	O
+light	O
+chains	O
+were	O
+not	O
+monitored	O
+in	O
+this	O
+study	O
+but	O
+were	O
+likely	O
+removed	O
+as	O
+well	O
+)	O
+[	O
+73	O
+]	O
+.	O
+
+Thus	O
+,	O
+at	O
+least	O
+with	O
+respect	O
+to	O
+ATPase	O
+activity	O
+,	O
+some	O
+dynein	O
+ACs	O
+do	O
+act	O
+as	O
+biochemical	O
+negative	O
+regulators	O
+of	O
+HC	O
+function	O
+.	O
+
+An	O
+Assortment	O
+of	O
+Essential	O
+and	O
+Nonessential	O
+Dynein	O
+Complexes	O
+
+Alternatively	O
+,	O
+an	O
+assortment	O
+of	O
+dynein	O
+complexes	O
+(	O
+with	O
+different	O
+ACs	O
+)	O
+could	O
+coexist	O
+within	O
+early	O
+embryonic	O
+cells	O
+,	O
+with	O
+only	O
+a	O
+subset	O
+required	O
+for	O
+the	O
+essential	O
+mitotic	O
+functions	O
+that	O
+require	O
+DHC	O
+-	O
+1	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+suppression	O
+might	O
+result	O
+from	O
+the	O
+release	O
+of	O
+DHC	O
+-	O
+1	O
+HCs	O
+from	O
+less	O
+essential	O
+motor	O
+complexes	O
+,	O
+allowing	O
+more	O
+of	O
+the	O
+functionally	O
+compromised	O
+HCs	O
+to	O
+participate	O
+in	O
+the	O
+essential	O
+process	O
+of	O
+mitosis	O
+.	O
+
+We	O
+currently	O
+disfavor	O
+this	O
+hypothesis	O
+because	O
+two	O
+of	O
+the	O
+suppressing	O
+light	O
+chains	O
+(	O
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+)	O
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+indeed	O
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+to	O
+meiotic	O
+and	O
+mitotic	O
+spindles	O
+(	O
+Figures	O
+6	O
+and	O
+7	O
+)	O
+,	O
+sites	O
+where	O
+DHC	O
+-	O
+1	O
+has	O
+been	O
+shown	O
+by	O
+others	O
+to	O
+localize	O
+and	O
+function	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+distribution	O
+of	O
+DYRB	O
+-	O
+1	O
+and	O
+DYLT	O
+-	O
+1	O
+closely	O
+resembles	O
+the	O
+distribution	O
+of	O
+the	O
+HC	O
+in	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+embryos	O
+,	O
+suggesting	O
+that	O
+these	O
+two	O
+light	O
+chains	O
+associate	O
+with	O
+the	O
+HC	O
+during	O
+mitosis	O
+(	O
+Figure	O
+7	O
+and	O
+[	O
+10	O
+]	O
+)	O
+.	O
+
+Finally	O
+,	O
+dhc	O
+-	O
+1	O
+-	O
+like	O
+phenotypes	O
+result	O
+from	O
+mutation	O
+or	O
+RNAi	O
+knockdown	O
+of	O
+three	O
+suppressing	O
+ACs	O
+in	O
+otherwise	O
+wild	O
+-	O
+type	O
+worms	B
+,	O
+indicating	O
+that	O
+they	O
+share	O
+at	O
+least	O
+some	O
+common	O
+and	O
+essential	O
+requirements	O
+.	O
+
+Regardless	O
+of	O
+the	O
+suppression	O
+mechanism	O
+,	O
+our	O
+identification	O
+of	O
+ACs	O
+that	O
+genetically	O
+interact	O
+with	O
+the	O
+DHC	O
+-	O
+1	O
+HC	O
+provides	O
+a	O
+basis	O
+for	O
+functionally	O
+classifying	O
+the	O
+paralogs	O
+of	O
+these	O
+dynein	O
+subunit	O
+gene	O
+families	O
+,	O
+and	O
+for	O
+further	O
+investigation	O
+of	O
+dynein	O
+composition	O
+and	O
+function	O
+.	O
+
+Nonessential	O
+Dynein	O
+Subunits	O
+and	O
+Negative	O
+Regulation	O
+of	O
+the	O
+HC	O
+
+Some	O
+ACs	O
+are	O
+nonessential	O
+,	O
+supporting	O
+the	O
+view	O
+that	O
+some	O
+cytoplasmic	O
+dynein	O
+subunits	O
+could	O
+function	O
+by	O
+exerting	O
+negative	O
+regulation	O
+on	O
+the	O
+HC	O
+,	O
+rather	O
+than	O
+positively	O
+influencing	O
+essential	O
+HC	O
+function	O
+.	O
+
+For	O
+example	O
+,	O
+DYRB	O
+-	O
+1	O
+is	O
+not	O
+absolutely	O
+required	O
+for	O
+viability	O
+because	O
+worms	B
+lacking	O
+this	O
+protein	O
+can	O
+be	O
+propagated	O
+,	O
+although	O
+they	O
+are	O
+extremely	O
+sick	O
+and	O
+do	O
+exhibit	O
+two	O
+dhc	O
+-	O
+1	O
+-	O
+like	O
+phenotypes	O
+(	O
+Figure	O
+8	O
+)	O
+.	O
+
+Also	O
+,	O
+homozygous	O
+dylt	O
+-	O
+1	O
+deletion	O
+mutants	O
+appear	O
+fully	O
+viable	O
+(	O
+Figure	O
+8	O
+)	O
+.	O
+
+The	O
+two	O
+additional	O
+Tctex1	O
+C	B
+.	I
+elegans	I
+genes	O
+could	O
+be	O
+functionally	O
+redundant	O
+with	O
+DYLT	O
+-	O
+1	O
+,	O
+but	O
+simultaneously	O
+reducing	O
+the	O
+function	O
+of	O
+DYLT	O
+-	O
+2	O
+and	O
+DYLT	O
+-	O
+3	O
+by	O
+RNAi	O
+in	O
+the	O
+dylt	O
+-	O
+1	O
+deletion	O
+strain	O
+did	O
+not	O
+cause	O
+lethality	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+Because	O
+RNAi	O
+does	O
+not	O
+always	O
+completely	O
+reduce	O
+function	O
+,	O
+the	O
+question	O
+of	O
+redundancy	O
+in	O
+the	O
+Tctex1	O
+C	B
+.	I
+elegans	I
+gene	O
+family	O
+remains	O
+unresolved	O
+.	O
+
+However	O
+,	O
+Drosophila	B
+contains	O
+only	O
+a	O
+single	O
+Tctex1	O
+gene	O
+,	O
+Dlc90F	O
+[	O
+74	O
+,	O
+75	O
+]	O
+.	O
+
+A	O
+Dlc90F	O
+null	O
+allele	O
+that	O
+deletes	O
+80	O
+%	O
+of	O
+the	O
+open	O
+reading	O
+frame	O
+is	O
+essential	O
+only	O
+for	O
+sperm	O
+production	O
+but	O
+not	O
+for	O
+viability	O
+of	O
+male	O
+or	O
+female	O
+flies	O
+,	O
+despite	O
+the	O
+wild	O
+-	O
+type	O
+protein	O
+being	O
+incorporated	O
+into	O
+dynein	O
+motors	O
+and	O
+expressed	O
+in	O
+various	O
+Drosophila	B
+tissues	O
+[	O
+74	O
+]	O
+.	O
+
+Thus	O
+,	O
+at	O
+least	O
+in	O
+Drosophila	B
+,	O
+the	O
+Tctex1	O
+dynein	O
+light	O
+chain	O
+family	O
+is	O
+not	O
+required	O
+for	O
+cell	O
+division	O
+processes	O
+like	O
+the	O
+HC	O
+is	O
+.	O
+
+Interestingly	O
+,	O
+budding	O
+yeast	B
+does	O
+not	O
+possess	O
+genes	O
+for	O
+the	O
+Tctex1	O
+or	O
+roadblock	O
+ACs	O
+,	O
+indicating	O
+that	O
+functional	O
+cytoplasmic	O
+dynein	O
+does	O
+not	O
+require	O
+these	O
+subunits	O
+that	O
+are	O
+conserved	O
+in	O
+many	O
+other	O
+organisms	O
+.	O
+
+The	O
+AC	O
+genes	O
+that	O
+yeast	B
+does	O
+posses	O
+are	O
+not	O
+required	O
+for	O
+HC	O
+motility	O
+in	O
+vitro	O
+because	O
+dynein	O
+purified	O
+from	O
+yeast	B
+with	O
+mutations	O
+in	O
+these	O
+genes	O
+remains	O
+fully	O
+active	O
+[	O
+2	O
+]	O
+.	O
+
+Thus	O
+,	O
+dynein	O
+function	O
+in	O
+several	O
+contexts	O
+does	O
+not	O
+require	O
+AC	O
+subunits	O
+,	O
+and	O
+we	O
+suggest	O
+that	O
+in	O
+some	O
+cases	O
+they	O
+may	O
+have	O
+negative	O
+regulatory	O
+roles	O
+.	O
+
+Negative	O
+regulation	O
+of	O
+cytoplasmic	O
+dynein	O
+may	O
+be	O
+redundant	O
+with	O
+other	O
+modes	O
+of	O
+HC	O
+regulation	O
+or	O
+only	O
+required	O
+during	O
+special	O
+circumstances	O
+.	O
+
+Further	O
+studies	O
+of	O
+subunit	O
+localization	O
+,	O
+and	O
+in	O
+vitro	O
+studies	O
+of	O
+C	B
+.	I
+elegans	I
+dynein	O
+motility	O
+,	O
+may	O
+provide	O
+further	O
+insight	O
+into	O
+the	O
+modes	O
+of	O
+AC	O
+regulation	O
+and	O
+function	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+C	B
+.	I
+elegans	I
+strains	O
+and	O
+culture	O
+.	O
+
+Strains	O
+were	O
+cultured	O
+according	O
+to	O
+standard	O
+procedures	O
+[	O
+28	O
+]	O
+.	O
+
+ts	O
+mutants	O
+were	O
+maintained	O
+at	O
+15	O
+degrees	O
+C	O
+and	O
+GFP	O
+-	O
+expressing	O
+strains	O
+in	O
+a	O
+wild	O
+-	O
+type	O
+background	O
+were	O
+maintained	O
+in	O
+a	O
+23	O
+degrees	O
+C	O
+incubator	O
+.	O
+
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+was	O
+outcrossed	O
+six	O
+times	O
+to	O
+the	O
+N2	O
+Bristol	O
+wild	O
+-	O
+type	O
+strain	O
+and	O
+the	O
+or283	O
+and	O
+or352	O
+dhc	O
+-	O
+1	O
+mutants	O
+were	O
+each	O
+outcrossed	O
+four	O
+times	O
+with	O
+N2	O
+.	O
+
+For	O
+sequencing	O
+mutant	O
+dhc	O
+-	O
+1	O
+loci	O
+,	O
+genomic	O
+DNA	O
+was	O
+amplified	O
+as	O
+overlapping	O
+~	O
+1	O
+-	O
+kb	O
+fragments	O
+from	O
+the	O
+start	O
+codon	O
+to	O
+the	O
+stop	O
+codon	O
+and	O
+sequenced	O
+at	O
+the	O
+University	O
+of	O
+Oregon	O
+DNA	O
+sequencing	O
+laboratory	O
+.	O
+
+For	O
+double	O
+mutant	O
+constructions	O
+,	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+mutation	O
+was	O
+monitored	O
+by	O
+sequencing	O
+or	O
+by	O
+assaying	O
+a	O
+restriction	O
+fragment	O
+length	O
+polymorphism	O
+caused	O
+by	O
+the	O
+mutation	O
+with	O
+Hpy188I	O
+(	O
+New	O
+England	O
+Biolabs	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+neb	O
+.	O
+com	O
+)	O
+,	O
+following	O
+PCR	O
+amplification	O
+of	O
+the	O
+mutated	O
+region	O
+.	O
+
+The	O
+dylt	O
+-	O
+1	O
+(	O
+ok417	O
+)	O
+and	O
+ufd	O
+-	O
+2	O
+(	O
+tm1380	O
+)	O
+alleles	O
+were	O
+monitored	O
+by	O
+PCR	O
+amplification	O
+of	O
+genomic	O
+sequence	O
+encompassing	O
+the	O
+deletions	O
+and	O
+assaying	O
+product	O
+size	O
+by	O
+agarose	O
+gel	O
+electrophoresis	O
+.	O
+
+GFP	O
+imaging	O
+.	O
+
+Visualization	O
+of	O
+GFP	O
+fusion	O
+protein	O
+localization	O
+was	O
+accomplished	O
+by	O
+mounting	O
+embryos	O
+on	O
+M9	O
++	O
+3	O
+%	O
+agarose	O
+pads	O
+on	O
+microscope	O
+slides	O
+covered	O
+with	O
+a	O
+coverslip	O
+.	O
+
+Time	O
+-	O
+lapse	O
+videos	O
+were	O
+obtained	O
+on	O
+a	O
+spinning	O
+disk	O
+Nikon	O
+Eclipse	O
+TE2000	O
+-	O
+U	O
+microscope	O
+(	O
+Nikon	O
+Instruments	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+nikon	O
+.	O
+com	O
+)	O
+fitted	O
+with	O
+an	O
+ORCA	O
+-	O
+ER	O
+digital	O
+camera	O
+(	O
+Hamamatsu	O
+Photonics	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+hamamatsu	O
+.	O
+com	O
+)	O
+using	O
+a	O
+Nikon	O
+60	O
+x	O
+,	O
+1	O
+.	O
+4	O
+NA	O
+Plan	O
+Apo	O
+oil	O
+objective	O
+lens	O
+.	O
+
+Videos	O
+were	O
+adjusted	O
+for	O
+contrast	O
+in	O
+ImageJ	O
+(	O
+National	O
+Institutes	O
+of	O
+Health	O
+,	O
+http	O
+:	O
+/	O
+/	O
+rsb	O
+.	O
+info	O
+.	O
+nih	O
+.	O
+gov	O
+/	O
+ij	O
+/	O
+)	O
+[	O
+76	O
+]	O
+,	O
+images	O
+were	O
+adjusted	O
+for	O
+levels	O
+in	O
+Adobe	O
+Photoshop	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+adobe	O
+.	O
+com	O
+/	O
+)	O
+.	O
+
+RNAi	O
+screening	O
+.	O
+
+After	O
+obtaining	O
+the	O
+E	B
+.	I
+coli	I
+RNAi	O
+library	O
+from	O
+the	O
+MRC	O
+Geneservice	O
+(	O
+Cambridge	O
+,	O
+UK	O
+)	O
+[	O
+17	O
+,	O
+19	O
+]	O
+,	O
+we	O
+rearrayed	O
+it	O
+into	O
+a	O
+48	O
+-	O
+well	O
+microplate	O
+format	O
+using	O
+a	O
+liquid	O
+-	O
+handling	O
+Qiagen	O
+BioRobot	O
+8000	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+qiagen	O
+.	O
+com	O
+)	O
+.	O
+
+E	B
+.	I
+coli	I
+strains	O
+were	O
+thawed	O
+from	O
+-	O
+80	O
+degrees	O
+C	O
+storage	O
+and	O
+inoculated	O
+into	O
+1	O
+ml	O
+of	O
+LB	O
++	O
+100	O
+mg	O
+/	O
+ml	O
+ampicillin	O
+-	O
+containing	O
+96	O
+-	O
+well	O
+growth	O
+plates	O
+(	O
+Whatman	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+whatman	O
+.	O
+com	O
+)	O
+and	O
+covered	O
+with	O
+microporous	O
+sealing	O
+film	O
+(	O
+USA	O
+Scientific	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+usascientific	O
+.	O
+com	O
+)	O
+.	O
+
+Only	O
+48	O
+wells	O
+of	O
+the	O
+96	O
+-	O
+well	O
+growth	O
+plates	O
+were	O
+filled	O
+with	O
+media	O
+,	O
+corresponding	O
+to	O
+the	O
+rearrayed	O
+E	B
+.	I
+coli	I
+library	O
+.	O
+
+After	O
+overnight	O
+shaking	O
+incubation	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+20	O
+mu	O
+l	O
+of	O
+the	O
+cultures	O
+were	O
+dispensed	O
+with	O
+a	O
+24	O
+-	O
+channel	O
+electronic	O
+repeating	O
+pipette	O
+(	O
+Rainin	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+rainin	O
+.	O
+com	O
+)	O
+onto	O
+48	O
+-	O
+well	O
+plates	O
+(	O
+Nunc	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+nuncbrand	O
+.	O
+com	O
+/	O
+)	O
+containing	O
+NGM	O
+agar	O
+,	O
+100	O
+mu	O
+g	O
+/	O
+ml	O
+ampicillin	O
+,	O
+and	O
+1	O
+mM	O
+IPTG	O
+and	O
+allowed	O
+to	O
+dry	O
+and	O
+induce	O
+dsRNA	O
+at	O
+37	O
+degrees	O
+C	O
+overnight	O
+.	O
+
+The	O
+48	O
+-	O
+well	O
+agar	O
+plates	O
+were	O
+filled	O
+with	O
+a	O
+Wheaton	O
+Unispense	O
+peristaltic	O
+pump	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+wheaton	O
+.	O
+com	O
+)	O
+equipped	O
+with	O
+a	O
+custom	O
+-	O
+made	O
+adaptor	O
+(	O
+University	O
+of	O
+Oregon	O
+Technical	O
+Science	O
+Administration	O
+)	O
+that	O
+allowed	O
+simultaneous	O
+filling	O
+of	O
+eight	O
+wells	O
+with	O
+the	O
+agar	O
+solution	O
+.	O
+
+Approximately	O
+15	O
+hypochlorite	O
+-	O
+synchronized	O
+L1	O
+mutant	O
+larvae	O
+were	O
+pipetted	O
+into	O
+each	O
+well	O
+of	O
+the	O
+48	O
+-	O
+well	O
+plates	O
+with	O
+a	O
+multichannel	O
+pipette	O
+and	O
+allowed	O
+to	O
+produce	O
+broods	O
+.	O
+
+Screening	O
+for	O
+F1	O
+viability	O
+was	O
+performed	O
+by	O
+visual	O
+examination	O
+with	O
+a	O
+dissecting	O
+microscope	O
+.	O
+
+Phenotypes	O
+were	O
+recorded	O
+on	O
+an	O
+Excel	O
+spreadsheet	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+microsoft	O
+.	O
+com	O
+)	O
+and	O
+organized	O
+in	O
+a	O
+FileMaker	O
+Pro	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+filemaker	O
+.	O
+com	O
+)	O
+database	O
+.	O
+
+We	O
+qualitatively	O
+identified	O
+295	O
+initial	O
+positive	O
+suppressing	O
+E	B
+.	I
+coli	I
+strains	O
+,	O
+for	O
+which	O
+we	O
+repeated	O
+the	O
+assay	O
+on	O
+60	O
+-	O
+mm	O
+plates	O
+with	O
+E	B
+.	I
+coli	I
+again	O
+thawed	O
+from	O
+the	O
+library	O
+(	O
+not	O
+streak	O
+purified	O
+)	O
+.	O
+
+If	O
+the	O
+observed	O
+phenotypes	O
+reproduced	O
+,	O
+the	O
+assay	O
+was	O
+performed	O
+with	O
+three	O
+streak	O
+-	O
+purified	O
+E	B
+.	I
+coli	I
+colonies	O
+,	O
+and	O
+a	O
+single	O
+isolate	O
+that	O
+again	O
+displayed	O
+the	O
+interaction	O
+was	O
+kept	O
+for	O
+further	O
+analysis	O
+.	O
+
+Embryonic	O
+viability	O
+quantitation	O
+methods	O
+.	O
+
+To	O
+quantitate	O
+embryonic	O
+viability	O
+we	O
+used	O
+the	O
+following	O
+procedure	O
+.	O
+
+Cultures	O
+of	O
+dsRNA	O
+-	O
+producing	O
+bacteria	O
+were	O
+grown	O
+overnight	O
+in	O
+LB	O
++	O
+100	O
+mu	O
+g	O
+/	O
+ml	O
+ampicillin	O
+.	O
+
+Cultures	O
+(	O
+0	O
+.	O
+2	O
+ml	O
+)	O
+were	O
+seeded	O
+onto	O
+60	O
+-	O
+mm	O
+NGM	O
+agar	O
+plates	O
+containing	O
+100	O
+mu	O
+g	O
+/	O
+ml	O
+ampicillin	O
+and	O
+1	O
+mM	O
+IPTG	O
+and	O
+allowed	O
+to	O
+induce	O
+dsRNAs	O
+overnight	O
+at	O
+room	O
+temperature	O
+.	O
+
+The	O
+L4440	O
+control	O
+vector	O
+-	O
+containing	O
+strain	O
+was	O
+used	O
+as	O
+the	O
+bacterial	O
+lawn	O
+for	O
+the	O
+experiments	O
+shown	O
+in	O
+Figures	O
+2A	O
+and	O
+3B	O
+.	O
+
+Approximately	O
+80	O
+synchronized	O
+L1	O
+larvae	O
+(	O
+obtained	O
+from	O
+hypochlorite	O
+-	O
+treated	O
+worms	B
+)	O
+were	O
+pipetted	O
+onto	O
+the	O
+plates	O
+and	O
+allowed	O
+to	O
+grow	O
+to	O
+young	O
+adulthood	O
+.	O
+
+Five	O
+gravid	O
+worms	B
+were	O
+transferred	O
+to	O
+prepared	O
+NGM	O
+agar	O
+plates	O
+supplemented	O
+with	O
+100	O
+mu	O
+g	O
+/	O
+ml	O
+ampicillin	O
+and	O
+1	O
+mM	O
+IPTG	O
+containing	O
+a	O
+small	O
+RNAi	O
+bacterial	O
+lawn	O
+produced	O
+from	O
+~	O
+5	O
+mu	O
+l	O
+of	O
+overnight	O
+E	B
+.	I
+coli	I
+culture	O
+.	O
+
+After	O
+producing	O
+broods	O
+,	O
+the	O
+adult	O
+worms	B
+were	O
+removed	O
+and	O
+the	O
+embryos	O
+were	O
+allowed	O
+to	O
+develop	O
+for	O
+at	O
+least	O
+24	O
+h	O
+.	O
+
+Embryos	O
+and	O
+larvae	O
+were	O
+then	O
+counted	O
+immediately	O
+or	O
+after	O
+storage	O
+at	O
+4	O
+degrees	O
+C	O
+.	O
+
+We	O
+considered	O
+only	O
+suppressor	O
+dsRNAs	O
+that	O
+increased	O
+embryonic	O
+viability	O
+greater	O
+than	O
+3	O
+-	O
+fold	O
+above	O
+the	O
+background	O
+viability	O
+observed	O
+with	O
+the	O
+L4440	O
+control	O
+vector	O
+(	O
+in	O
+the	O
+dhc	O
+-	O
+1	O
+(	O
+or195	O
+)	O
+)	O
+screen	O
+to	O
+be	O
+significant	O
+enough	O
+for	O
+continued	O
+study	O
+.	O
+
+Molecular	O
+biology	O
+.	O
+
+We	O
+introduced	O
+a	O
+polylinker	O
+site	O
+containing	O
+six	O
+unique	O
+restriction	O
+enzyme	O
+recognition	O
+sites	O
+into	O
+the	O
+pIC26	O
+GFP	O
+-	O
+S	O
+protein	O
+plasmid	O
+by	O
+using	O
+phosphorylated	O
+and	O
+PAGE	O
+-	O
+purified	O
+synthetic	O
+oligonucleotides	O
+[	O
+77	O
+]	O
+.	O
+
+Following	O
+ligation	O
+,	O
+the	O
+new	O
+plasmid	O
+was	O
+sequence	O
+verified	O
+.	O
+
+The	O
+modified	O
+vector	O
+,	O
+pSO26	O
+,	O
+allows	O
+the	O
+use	O
+of	O
+additional	O
+restriction	O
+enzymes	O
+and	O
+directional	O
+cloning	O
+for	O
+inserting	O
+genes	O
+of	O
+interest	O
+(	O
+Figure	O
+S2	O
+)	O
+.	O
+
+The	O
+SpeI	O
+site	O
+was	O
+recreated	O
+at	O
+the	O
+5	O
+'	O
+end	O
+of	O
+the	O
+polylinker	O
+but	O
+not	O
+at	O
+the	O
+3	O
+'	O
+end	O
+.	O
+
+We	O
+amplified	O
+N2	O
+genomic	O
+DNA	O
+or	O
+cDNA	O
+(	O
+Invitrogen	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+invitrogen	O
+.	O
+com	O
+)	O
+with	O
+Pfu	O
+Turbo	O
+polymerase	O
+(	O
+Stratagene	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+stratagene	O
+.	O
+com	O
+)	O
+,	O
+and	O
+cloned	O
+A	O
+-	O
+tailed	O
+PCR	O
+products	O
+into	O
+either	O
+pGEM	O
+-	O
+T	O
+or	O
+pGEM	O
+-	O
+T	O
+-	O
+easy	O
+shuttle	O
+vectors	O
+(	O
+Promega	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+promega	O
+.	O
+com	O
+)	O
+.	O
+
+Inserted	O
+genes	O
+were	O
+sequence	O
+verified	O
+at	O
+the	O
+University	O
+of	O
+Oregon	O
+DNA	O
+sequencing	O
+laboratory	O
+prior	O
+to	O
+cleavage	O
+and	O
+ligation	O
+to	O
+pSO26	O
+(	O
+see	O
+Table	O
+S3	O
+for	O
+restriction	O
+sites	O
+and	O
+primer	O
+sequences	O
+used	O
+)	O
+.	O
+
+All	O
+of	O
+the	O
+constructs	O
+used	O
+in	O
+this	O
+study	O
+were	O
+cloned	O
+as	O
+SpeI	O
+-	O
+AsiSI	O
+or	O
+AscI	O
+-	O
+AsiSI	O
+fragments	O
+,	O
+except	O
+for	O
+the	O
+STAR	O
+-	O
+2	O
+gene	O
+,	O
+which	O
+was	O
+amplified	O
+as	O
+a	O
+SpeI	O
+fragment	O
+and	O
+cloned	O
+into	O
+pIC26	O
+.	O
+
+To	O
+construct	O
+dynein	O
+subunit	O
+dsRNA	O
+-	O
+expressing	O
+plasmids	O
+not	O
+available	O
+in	O
+the	O
+RNAi	O
+library	O
+,	O
+gene	O
+fragments	O
+were	O
+amplified	O
+from	O
+N2	O
+genomic	O
+DNA	O
+with	O
+the	O
+following	O
+primers	O
+:	O
+F41G4	O
+.	O
+1	O
+:	O
+5	O
+'	O
+-	O
+AAGATATCACCCAAAATGGT	O
+-	O
+3	O
+'	O
+and	O
+5	O
+'	O
+-	O
+CGGATATCTCGACTGAAGCT	O
+-	O
+3	O
+'	O
+,	O
+xbx	O
+-	O
+1	O
+:	O
+5	O
+'	O
+-	O
+AAGATATCTACGACGATGGA	O
+-	O
+3	O
+'	O
+and	O
+5	O
+'	O
+-	O
+CGGATATCCGTGCCTCTGCA	O
+-	O
+3	O
+'	O
+,	O
+dlc	O
+-	O
+3	O
+:	O
+5	O
+'	O
+-	O
+AAGATATCAATTTCAGGTGG	O
+-	O
+3	O
+'	O
+and	O
+5	O
+'	O
+-	O
+CGGATATCAGCACACTTGCA	O
+-	O
+3	O
+'	O
+.	O
+
+The	O
+PCR	O
+products	O
+were	O
+cut	O
+with	O
+EcoRV	O
+,	O
+ligated	O
+to	O
+EcoRV	O
+-	O
+digested	O
+L4440	O
+,	O
+and	O
+sequence	O
+verified	O
+.	O
+
+Isolation	O
+of	O
+transgenic	O
+worms	B
+.	O
+
+GFP	O
+fusion	O
+plasmids	O
+were	O
+bombarded	O
+into	O
+unc	O
+-	O
+119	O
+(	O
+ed3	O
+)	O
+worms	B
+as	O
+previously	O
+described	O
+except	O
+with	O
+the	O
+following	O
+two	O
+changes	O
+[	O
+78	O
+]	O
+.	O
+
+Three	O
+milligrams	O
+of	O
+gold	O
+particles	O
+were	O
+used	O
+per	O
+hepta	O
+adaptor	O
+bombardment	O
+.	O
+
+Also	O
+,	O
+we	O
+briefly	O
+sonicated	O
+the	O
+gold	O
+particles	O
+(	O
+prior	O
+to	O
+DNA	O
+coating	O
+and	O
+while	O
+suspended	O
+in	O
+50	O
+%	O
+glycerol	O
+)	O
+with	O
+a	O
+Branson	O
+sonifier	O
+450	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+sonifier	O
+.	O
+com	O
+/	O
+)	O
+fitted	O
+with	O
+a	O
+small	O
+tip	O
+set	O
+to	O
+power	O
+level	O
+1	O
+,	O
+to	O
+disrupt	O
+gold	O
+aggregates	O
+.	O
+
+Non	O
+-	O
+Unc	O
+worms	B
+were	O
+picked	O
+to	O
+new	O
+plates	O
+and	O
+allowed	O
+to	O
+produce	O
+broods	O
+,	O
+which	O
+were	O
+assayed	O
+for	O
+GFP	O
+fluorescence	O
+with	O
+a	O
+Zeiss	O
+axioskop	O
+microscope	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+zeiss	O
+.	O
+com	O
+/	O
+)	O
+fitted	O
+with	O
+an	O
+X	O
+-	O
+Cite	O
+120	O
+illumination	O
+system	O
+(	O
+EXFO	O
+life	O
+sciences	O
+,	O
+Mississauga	O
+,	O
+Ontario	O
+,	O
+Canada	O
+)	O
+.	O
+
+For	O
+each	O
+fluorescent	O
+line	O
+,	O
+12	O
+GFP	O
+-	O
+positive	O
+worms	B
+were	O
+singled	O
+to	O
+new	O
+plates	O
+to	O
+determine	O
+if	O
+the	O
+constructs	O
+were	O
+integrated	O
+or	O
+were	O
+carried	O
+as	O
+extrachromosomal	O
+arrays	O
+.	O
+
+Supporting	O
+Information	O
+
+Accession	O
+Numbers	O
+
+The	O
+National	O
+Center	O
+for	O
+Biotechnology	O
+Information	O
+(	O
+NCBI	O
+)	O
+database	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+ncbi	O
+.	O
+nlm	O
+.	O
+nih	O
+.	O
+gov	O
+/	O
+gquery	O
+/	O
+gquery	O
+.	O
+fcgi	O
+?	O
+itool	O
+=	O
+toolbar	O
+)	O
+accession	O
+numbers	O
+for	O
+the	O
+dhc	O
+-	O
+1	O
+homologs	O
+discussed	O
+in	O
+this	O
+paper	O
+are	O
+C	B
+.	I
+elegans	I
+,	O
+NP	O
+_	O
+491363	O
+;	O
+Dictyostelium	B
+discoideum	I
+,	O
+XP	O
+_	O
+643185	O
+;	O
+Drosophila	B
+melanogaster	I
+,	O
+AAA60323	O
+;	O
+Homo	B
+sapiens	I
+,	O
+NP	O
+_	O
+001367	O
+;	O
+Mus	B
+musculus	I
+,	O
+NP	O
+_	O
+084514	O
+;	O
+Saccharomyces	B
+cerevisiae	I
+,	O
+NP	O
+_	O
+012980	O
+;	O
+and	O
+Schizosaccharomyces	B
+pombe	I
+,	O
+NP	O
+_	O
+001018285	O
+.	O
+
+The	O
+NCBI	O
+accession	O
+numbers	O
+for	O
+the	O
+Drosophila	B
+and	O
+human	B
+DYLT	O
+-	O
+1	O
+and	O
+DYRB	O
+-	O
+1	O
+protein	O
+homologues	O
+,	O
+respectively	O
+,	O
+are	O
+Dlc90F	O
+,	O
+NP	O
+_	O
+477356	O
+;	O
+DYNLT3	O
+,	O
+NP	O
+_	O
+006511	O
+;	O
+DYNLRB1	O
+,	O
+NP	O
+_	O
+054902	O
+;	O
+and	O
+robl	O
+,	O
+NP	O
+_	O
+523771	O
+.	O
+
+Identification	O
+of	O
+Two	O
+Independent	O
+Risk	O
+Factors	O
+for	O
+Lupus	O
+within	O
+the	O
+MHC	O
+in	O
+United	O
+Kingdom	O
+Families	O
+
+Abstract	O
+
+The	O
+association	O
+of	O
+the	O
+major	O
+histocompatibility	O
+complex	O
+(	O
+MHC	O
+)	O
+with	O
+SLE	O
+is	O
+well	O
+established	O
+yet	O
+the	O
+causal	O
+variants	O
+arising	O
+from	O
+this	O
+region	O
+remain	O
+to	O
+be	O
+identified	O
+,	O
+largely	O
+due	O
+to	O
+inadequate	O
+study	O
+design	O
+and	O
+the	O
+strong	O
+linkage	O
+disequilibrium	O
+demonstrated	O
+by	O
+genes	O
+across	O
+this	O
+locus	O
+.	O
+
+The	O
+majority	O
+of	O
+studies	O
+thus	O
+far	O
+have	O
+identified	O
+strong	O
+association	O
+with	O
+classical	O
+class	O
+II	O
+alleles	O
+,	O
+in	O
+particular	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+and	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+.	O
+
+Additional	O
+associations	O
+have	O
+been	O
+reported	O
+with	O
+class	O
+III	O
+alleles	O
+;	O
+specifically	O
+,	O
+complement	O
+C4	O
+null	O
+alleles	O
+and	O
+a	O
+tumor	O
+necrosis	O
+factor	O
+promoter	O
+SNP	O
+(	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+relative	O
+effects	O
+of	O
+these	O
+class	O
+II	O
+and	O
+class	O
+III	O
+variants	O
+have	O
+not	O
+been	O
+determined	O
+.	O
+
+We	O
+have	O
+thus	O
+used	O
+a	O
+family	O
+-	O
+based	O
+approach	O
+to	O
+map	O
+association	O
+signals	O
+across	O
+the	O
+MHC	O
+class	O
+II	O
+and	O
+class	O
+III	O
+regions	O
+in	O
+a	O
+cohort	O
+of	O
+314	O
+complete	O
+United	O
+Kingdom	O
+Caucasian	O
+SLE	O
+trios	O
+by	O
+typing	O
+tagging	O
+SNPs	O
+together	O
+with	O
+classical	O
+typing	O
+of	O
+the	O
+HLA	O
+-	O
+DRB1	O
+locus	O
+.	O
+
+Using	O
+TDT	O
+and	O
+conditional	O
+regression	O
+analyses	O
+,	O
+we	O
+have	O
+demonstrated	O
+the	O
+presence	O
+of	O
+two	O
+distinct	O
+and	O
+independent	O
+association	O
+signals	O
+in	O
+SLE	O
+:	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+(	O
+nominal	O
+p	O
+=	O
+4	O
+.	O
+9	O
+x	O
+10	O
+-	O
+8	O
+,	O
+permuted	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+,	O
+OR	O
+=	O
+2	O
+.	O
+3	O
+)	O
+and	O
+the	O
+T	O
+allele	O
+of	O
+SNP	O
+rs419788	O
+(	O
+nominal	O
+p	O
+=	O
+4	O
+.	O
+3	O
+x	O
+10	O
+-	O
+8	O
+,	O
+permuted	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+,	O
+OR	O
+=	O
+2	O
+.	O
+0	O
+)	O
+in	O
+intron	O
+6	O
+of	O
+the	O
+class	O
+III	O
+region	O
+gene	O
+SKIV2L	O
+.	O
+
+Assessment	O
+of	O
+genotypic	O
+risk	O
+demonstrates	O
+a	O
+likely	O
+dominant	O
+model	O
+of	O
+inheritance	O
+for	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+,	O
+while	O
+rs419788	O
+-	O
+T	O
+confers	O
+susceptibility	O
+in	O
+an	O
+additive	O
+manner	O
+.	O
+
+Furthermore	O
+,	O
+by	O
+comparing	O
+transmitted	O
+and	O
+untransmitted	O
+parental	O
+chromosomes	O
+,	O
+we	O
+have	O
+delimited	O
+our	O
+class	O
+II	O
+signal	O
+to	O
+a	O
+180	O
+kb	O
+region	O
+encompassing	O
+the	O
+alleles	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+HLA	O
+-	O
+DQA1	O
+*	O
+0501	O
+-	O
+HLA	O
+-	O
+DQB1	O
+*	O
+0201	O
+alone	O
+.	O
+
+Our	O
+class	O
+III	O
+signal	O
+importantly	O
+excludes	O
+independent	O
+association	O
+at	O
+the	O
+TNF	O
+promoter	O
+polymorphism	O
+,	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+,	O
+in	O
+our	O
+SLE	O
+cohort	O
+and	O
+provides	O
+a	O
+potentially	O
+novel	O
+locus	O
+for	O
+future	O
+genetic	O
+and	O
+functional	O
+studies	O
+.	O
+
+Systemic	O
+lupus	O
+erythematosus	O
+(	O
+SLE	O
+/	O
+lupus	O
+)	O
+is	O
+a	O
+complex	O
+autoimmune	O
+disease	O
+in	O
+which	O
+the	O
+body	O
+'	O
+s	O
+immune	O
+system	O
+attacks	O
+its	O
+own	O
+tissues	O
+,	O
+causing	O
+inflammation	O
+in	O
+a	O
+variety	O
+of	O
+different	O
+organs	O
+such	O
+as	O
+the	O
+skin	O
+,	O
+joints	O
+,	O
+and	O
+kidneys	O
+.	O
+
+The	O
+cause	O
+of	O
+lupus	O
+is	O
+not	O
+known	O
+,	O
+but	O
+genes	O
+play	O
+a	O
+significant	O
+role	O
+in	O
+the	O
+predisposition	O
+to	O
+disease	O
+.	O
+
+The	O
+major	O
+histocompatibility	O
+complex	O
+(	O
+MHC	O
+)	O
+on	O
+Chromosome	O
+6	O
+contains	O
+at	O
+least	O
+100	O
+different	O
+genes	O
+that	O
+affect	O
+the	O
+immune	O
+system	O
+,	O
+including	O
+the	O
+genes	O
+with	O
+the	O
+strongest	O
+effect	O
+on	O
+lupus	O
+susceptibility	O
+.	O
+
+Despite	O
+the	O
+importance	O
+of	O
+the	O
+MHC	O
+in	O
+SLE	O
+,	O
+the	O
+identity	O
+of	O
+the	O
+actual	O
+genes	O
+in	O
+the	O
+MHC	O
+region	O
+that	O
+cause	O
+SLE	O
+has	O
+remained	O
+elusive	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+used	O
+the	O
+latest	O
+set	O
+of	O
+genetic	O
+markers	O
+present	O
+at	O
+the	O
+MHC	O
+in	O
+lupus	O
+families	O
+to	O
+identify	O
+the	O
+actual	O
+genes	O
+that	O
+affect	O
+the	O
+disease	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+we	O
+have	O
+shown	O
+for	O
+the	O
+first	O
+time	O
+that	O
+two	O
+separate	O
+groups	O
+of	O
+genes	O
+are	O
+involved	O
+in	O
+SLE	O
+.	O
+
+One	O
+group	O
+of	O
+genes	O
+alters	O
+how	O
+the	O
+immune	O
+system	O
+may	O
+inappropriately	O
+target	O
+its	O
+own	O
+tissues	O
+in	O
+the	O
+disease	O
+.	O
+
+How	O
+the	O
+second	O
+set	O
+of	O
+genes	O
+predisposes	O
+to	O
+SLE	O
+is	O
+the	O
+subject	O
+of	O
+ongoing	O
+study	O
+.	O
+
+Introduction	O
+
+Since	O
+the	O
+early	O
+1970s	O
+,	O
+the	O
+human	B
+major	O
+histocompatibility	O
+complex	O
+(	O
+MHC	O
+)	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+associated	O
+with	O
+a	O
+number	O
+of	O
+autoimmune	O
+,	O
+inflammatory	O
+,	O
+and	O
+infectious	O
+diseases	O
+,	O
+and	O
+it	O
+continues	O
+to	O
+be	O
+the	O
+focus	O
+of	O
+intense	O
+research	O
+[	O
+1	O
+]	O
+.	O
+
+The	O
+recently	O
+defined	O
+extended	O
+MHC	O
+(	O
+xMHC	O
+)	O
+encompasses	O
+7	O
+.	O
+6	O
+Mb	O
+of	O
+genome	O
+on	O
+6p21	O
+.	O
+3	O
+and	O
+is	O
+divided	O
+into	O
+five	O
+subregions	O
+from	O
+telomere	O
+to	O
+centromere	O
+:	O
+extended	O
+class	O
+I	O
+,	O
+classical	O
+class	O
+I	O
+,	O
+classical	O
+class	O
+III	O
+,	O
+classical	O
+class	O
+II	O
+,	O
+and	O
+extended	O
+class	O
+II	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+MHC	O
+contains	O
+two	O
+hypervariable	O
+regions	O
+,	O
+the	O
+RCCX	O
+module	O
+in	O
+class	O
+III	O
+(	O
+spanning	O
+complement	O
+C4	O
+)	O
+and	O
+the	O
+HLA	O
+-	O
+DRB	O
+genes	O
+in	O
+class	O
+II	O
+,	O
+that	O
+both	O
+exhibit	O
+copy	O
+number	O
+polymorphism	O
+.	O
+
+Examination	O
+of	O
+the	O
+sequence	O
+across	O
+the	O
+extended	O
+MHC	O
+reveals	O
+the	O
+presence	O
+of	O
+421	O
+genes	O
+,	O
+and	O
+over	O
+252	O
+(	O
+60	O
+%	O
+)	O
+are	O
+thought	O
+to	O
+be	O
+expressed	O
+[	O
+2	O
+]	O
+.	O
+
+Around	O
+40	O
+%	O
+of	O
+genes	O
+expressed	O
+within	O
+the	O
+classical	O
+MHC	O
+encode	O
+proteins	O
+with	O
+putative	O
+immunomodulatory	O
+function	O
+[	O
+3	O
+]	O
+.	O
+
+The	O
+classical	O
+class	O
+I	O
+and	O
+class	O
+II	O
+loci	O
+encode	O
+the	O
+human	B
+leucocyte	O
+antigen	O
+(	O
+HLA	O
+)	O
+proteins	O
+involved	O
+in	O
+antigen	O
+presentation	O
+to	O
+T	O
+cells	O
+,	O
+initiating	O
+the	O
+adaptive	O
+immune	O
+response	O
+.	O
+
+The	O
+class	O
+III	O
+region	O
+contains	O
+the	O
+greatest	O
+density	O
+of	O
+genes	O
+in	O
+the	O
+genome	O
+(	O
+58	O
+expressed	O
+genes	O
+)	O
+,	O
+which	O
+are	O
+often	O
+found	O
+in	O
+functionally	O
+related	O
+clusters	O
+[	O
+2	O
+]	O
+.	O
+
+A	O
+major	O
+obstacle	O
+in	O
+the	O
+identification	O
+of	O
+disease	O
+-	O
+specific	O
+causal	O
+variants	O
+within	O
+the	O
+MHC	O
+has	O
+been	O
+the	O
+strong	O
+linkage	O
+disequilibrium	O
+(	O
+LD	O
+)	O
+exhibited	O
+by	O
+certain	O
+alleles	O
+in	O
+this	O
+region	O
+,	O
+resulting	O
+in	O
+the	O
+existence	O
+of	O
+long	O
+-	O
+range	O
+,	O
+conserved	O
+,	O
+extended	O
+haplotypes	O
+[	O
+4	O
+]	O
+,	O
+also	O
+known	O
+as	O
+ancestral	O
+haplotypes	O
+[	O
+5	O
+]	O
+,	O
+sometimes	O
+spanning	O
+more	O
+than	O
+2	O
+Mb	O
+[	O
+6	O
+]	O
+.	O
+
+Thus	O
+,	O
+for	O
+many	O
+MHC	O
+-	O
+associated	O
+diseases	O
+,	O
+it	O
+has	O
+only	O
+been	O
+possible	O
+to	O
+delimit	O
+association	O
+signals	O
+to	O
+a	O
+particular	O
+extended	O
+haplotype	O
+or	O
+segment	O
+of	O
+one	O
+.	O
+
+Systemic	O
+lupus	O
+erythematosus	O
+(	O
+SLE	O
+/	O
+lupus	O
+,	O
+[	O
+Online	O
+Mendelian	O
+Inheritance	O
+in	O
+Man	B
+152700	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+ncbi	O
+.	O
+nlm	O
+.	O
+nih	O
+.	O
+gov	O
+/	O
+sites	O
+/	O
+entrez	O
+?	O
+db	O
+=	O
+OMIM	O
+&	O
+TabCmd	O
+=	O
+Limits	O
+]	O
+)	O
+is	O
+a	O
+chronic	O
+,	O
+multi	O
+-	O
+system	O
+autoimmune	O
+disease	O
+affecting	O
+young	O
+women	B
+ten	O
+times	O
+more	O
+commonly	O
+than	O
+men	B
+.	O
+
+The	O
+worldwide	O
+prevalence	O
+of	O
+SLE	O
+is	O
+estimated	O
+at	O
+between	O
+12	O
+and	O
+124	O
+cases	O
+per	O
+100	O
+,	O
+000	O
+individuals	O
+[	O
+7	O
+]	O
+.	O
+
+SLE	O
+is	O
+characterized	O
+by	O
+the	O
+presence	O
+of	O
+pathogenic	O
+autoantibodies	O
+to	O
+nuclear	O
+and	O
+cell	O
+-	O
+surface	O
+antigens	O
+that	O
+show	O
+affinity	O
+maturation	O
+.	O
+
+The	O
+consequent	O
+immune	O
+complexes	O
+deposit	O
+in	O
+tissues	O
+,	O
+causing	O
+inflammation	O
+and	O
+damage	O
+.	O
+
+It	O
+is	O
+well	O
+established	O
+that	O
+there	O
+is	O
+a	O
+complex	O
+genetic	O
+component	O
+to	O
+lupus	O
+aetiology	O
+,	O
+with	O
+hormonal	O
+and	O
+environmental	O
+influences	O
+also	O
+contributing	O
+to	O
+disease	O
+susceptibility	O
+[	O
+8	O
+,	O
+9	O
+]	O
+.	O
+
+The	O
+MHC	O
+has	O
+been	O
+the	O
+most	O
+consistently	O
+confirmed	O
+genetic	O
+risk	O
+factor	O
+for	O
+SLE	O
+,	O
+and	O
+multiple	O
+different	O
+genes	O
+within	O
+the	O
+region	O
+have	O
+been	O
+significantly	O
+implicated	O
+with	O
+disease	O
+susceptibility	O
+.	O
+
+For	O
+example	O
+,	O
+hereditary	O
+and	O
+acquired	O
+deficiencies	O
+of	O
+the	O
+early	O
+classical	O
+complement	O
+component	O
+C4	O
+,	O
+located	O
+within	O
+the	O
+MHC	O
+class	O
+III	O
+locus	O
+,	O
+leads	O
+to	O
+a	O
+lupus	O
+-	O
+like	O
+syndrome	O
+.	O
+
+A	O
+role	O
+for	O
+another	O
+class	O
+III	O
+gene	O
+,	O
+tumour	O
+necrosis	O
+factor	O
+alpha	O
+(	O
+TNF	O
+)	O
+,	O
+in	O
+SLE	O
+was	O
+suggested	O
+following	O
+the	O
+observation	O
+that	O
+the	O
+lupus	O
+-	O
+prone	O
+New	O
+Zealand	O
+F1	O
+mouse	B
+hybrid	O
+exhibits	O
+constitutively	O
+low	O
+TNF	O
+expression	O
+[	O
+10	O
+]	O
+.	O
+
+Recently	O
+,	O
+the	O
+development	O
+of	O
+antinuclear	O
+antibodies	O
+in	O
+patients	B
+treated	O
+with	O
+TNF	O
+antagonists	O
+has	O
+also	O
+stimulated	O
+interest	O
+in	O
+the	O
+possible	O
+role	O
+of	O
+TNF	O
+in	O
+SLE	O
+[	O
+11	O
+-	O
+13	O
+]	O
+.	O
+
+Murine	O
+and	O
+human	B
+candidate	O
+gene	O
+studies	O
+,	O
+together	O
+with	O
+genome	O
+-	O
+wide	O
+linkage	O
+screens	O
+,	O
+provide	O
+further	O
+support	O
+that	O
+multiple	O
+genetic	O
+loci	O
+,	O
+including	O
+the	O
+mouse	B
+MHC	O
+complex	O
+H2	O
+and	O
+the	O
+human	B
+MHC	O
+locus	O
+,	O
+contribute	O
+to	O
+disease	O
+susceptibility	O
+[	O
+14	O
+-	O
+17	O
+]	O
+.	O
+
+It	O
+should	O
+be	O
+noted	O
+that	O
+the	O
+human	B
+MHC	O
+was	O
+first	O
+associated	O
+with	O
+SLE	O
+in	O
+1971	O
+,	O
+when	O
+studies	O
+demonstrated	O
+that	O
+lupus	O
+probands	O
+were	O
+enriched	O
+for	O
+the	O
+class	O
+I	O
+alleles	O
+HL	O
+-	O
+A8	O
+(	O
+now	O
+known	O
+as	O
+HLA	O
+-	O
+B8	O
+)	O
+and	O
+HLA	O
+-	O
+W15	O
+(	O
+now	O
+known	O
+as	O
+HLA	O
+-	O
+B15	O
+)	O
+when	O
+compared	O
+with	O
+healthy	O
+controls	O
+[	O
+18	O
+,	O
+19	O
+]	O
+.	O
+
+Further	O
+case	O
+control	O
+association	O
+studies	O
+were	O
+small	O
+,	O
+performed	O
+in	O
+ethnically	O
+diverse	O
+populations	O
+,	O
+and	O
+tested	O
+only	O
+a	O
+small	O
+number	O
+of	O
+the	O
+classical	O
+HLA	O
+and	O
+complement	O
+C4	O
+alleles	O
+.	O
+
+The	O
+most	O
+consistent	O
+findings	O
+reported	O
+to	O
+date	O
+are	O
+associations	O
+with	O
+the	O
+class	O
+II	O
+alleles	O
+HLA	O
+-	O
+DR2	O
+(	O
+DRB1	O
+*	O
+1501	O
+)	O
+and	O
+HLA	O
+-	O
+DR3	O
+(	O
+DRB1	O
+*	O
+0301	O
+)	O
+and	O
+their	O
+respective	O
+haplotypes	O
+in	O
+Caucasian	O
+populations	O
+.	O
+
+The	O
+complement	O
+C4A	O
+null	O
+allele	O
+(	O
+C4A	O
+*	O
+Q0	O
+)	O
+has	O
+shown	O
+inconsistent	O
+association	O
+with	O
+lupus	O
+in	O
+a	O
+number	O
+of	O
+studies	O
+-	O
+-	O
+a	O
+situation	O
+that	O
+may	O
+reflect	O
+genetic	O
+heterogeneity	O
+in	O
+disease	O
+susceptibility	O
+[	O
+20	O
+-	O
+23	O
+]	O
+.	O
+
+In	O
+addition	O
+,	O
+a	O
+recent	O
+study	O
+has	O
+demonstrated	O
+that	O
+low	O
+C4A	O
+copy	O
+number	O
+is	O
+a	O
+risk	O
+factor	O
+for	O
+lupus	O
+in	O
+a	O
+European	O
+American	O
+cohort	O
+[	O
+24	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+C4A	O
+null	O
+allele	O
+lies	O
+on	O
+the	O
+lupus	O
+-	O
+associated	O
+DR3	O
+"	O
+autoimmune	O
+"	O
+extended	O
+haplotype	O
+(	O
+AH8	O
+.	O
+1	O
+)	O
+,	O
+which	O
+exhibits	O
+extremely	O
+strong	O
+LD	O
+[	O
+6	O
+]	O
+.	O
+
+It	O
+therefore	O
+remains	O
+to	O
+be	O
+definitively	O
+established	O
+whether	O
+this	O
+locus	O
+constitutes	O
+a	O
+distinct	O
+susceptibility	O
+allele	O
+to	O
+that	O
+of	O
+the	O
+class	O
+II	O
+association	O
+or	O
+is	O
+merely	O
+in	O
+LD	O
+with	O
+it	O
+.	O
+
+Similarly	O
+,	O
+certain	O
+TNF	O
+promoter	O
+polymorphisms	O
+,	O
+including	O
+the	O
+much	O
+-	O
+studied	O
+SNP	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+,	O
+have	O
+shown	O
+association	O
+with	O
+SLE	O
+;	O
+but	O
+again	O
+,	O
+many	O
+of	O
+these	O
+variants	O
+are	O
+carried	O
+on	O
+the	O
+highly	O
+conserved	O
+8	O
+.	O
+1	O
+ancestral	O
+haplotype	O
+,	O
+thus	O
+restricting	O
+interpretation	O
+of	O
+these	O
+data	O
+.	O
+
+In	O
+2002	O
+,	O
+a	O
+family	O
+-	O
+based	O
+study	O
+employing	O
+microsatellites	O
+as	O
+surrogate	O
+markers	O
+for	O
+HLA	O
+-	O
+DRB1	O
+haplotypes	O
+in	O
+Caucasian	O
+lupus	O
+families	O
+demonstrated	O
+association	O
+with	O
+DR3	O
+-	O
+,	O
+DR2	O
+-	O
+,	O
+and	O
+DR8	O
+(	O
+DRB1	O
+*	O
+0801	O
+)	O
+-	O
+containing	O
+haplotypes	O
+.	O
+
+In	O
+that	O
+study	O
+,	O
+Graham	O
+and	O
+colleagues	O
+reported	O
+that	O
+,	O
+taking	O
+advantage	O
+of	O
+recombinant	O
+chromosomes	O
+,	O
+the	O
+disease	O
+risk	O
+region	O
+could	O
+be	O
+limited	O
+to	O
+a	O
+1	O
+Mb	O
+region	O
+encompassing	O
+classical	O
+class	O
+II	O
+and	O
+class	O
+III	O
+[	O
+25	O
+]	O
+.	O
+
+We	O
+have	O
+performed	O
+a	O
+medium	O
+resolution	O
+association	O
+mapping	O
+study	O
+of	O
+the	O
+MHC	O
+in	O
+lupus	O
+families	O
+,	O
+utilizing	O
+a	O
+combination	O
+of	O
+SNPs	O
+and	O
+four	O
+-	O
+digit	O
+typing	O
+at	O
+the	O
+HLA	O
+-	O
+DRB1	O
+locus	O
+in	O
+order	O
+to	O
+anchor	O
+haplotypes	O
+.	O
+
+Sixty	O
+-	O
+eight	O
+SNPs	O
+were	O
+successfully	O
+genotyped	O
+across	O
+a	O
+2	O
+.	O
+4	O
+Mb	O
+region	O
+of	O
+the	O
+MHC	O
+,	O
+from	O
+the	O
+class	O
+I	O
+locus	O
+KIAA1949	O
+to	O
+the	O
+class	O
+II	O
+gene	O
+HLA	O
+-	O
+DPB2	O
+,	O
+in	O
+314	O
+UK	O
+Caucasian	O
+SLE	O
+trios	O
+.	O
+
+We	O
+used	O
+these	O
+data	O
+to	O
+perform	O
+a	O
+family	O
+-	O
+based	O
+association	O
+study	O
+in	O
+an	O
+attempt	O
+to	O
+distinguish	O
+the	O
+relative	O
+effects	O
+of	O
+the	O
+class	O
+II	O
+and	O
+class	O
+III	O
+regions	O
+of	O
+the	O
+MHC	O
+in	O
+lupus	O
+susceptibility	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+employed	O
+the	O
+long	O
+-	O
+range	O
+haplotype	O
+test	O
+to	O
+search	O
+for	O
+the	O
+presence	O
+of	O
+high	O
+-	O
+frequency	O
+,	O
+extended	O
+haplotypes	O
+indicative	O
+of	O
+recent	O
+positive	O
+selection	O
+[	O
+26	O
+]	O
+.	O
+
+We	O
+have	O
+also	O
+used	O
+family	O
+-	O
+based	O
+and	O
+case	O
+-	O
+control	O
+strategies	O
+to	O
+examine	O
+genotypic	O
+risk	O
+at	O
+HLA	O
+-	O
+DRB1	O
+and	O
+rs419788	O
+.	O
+
+Results	O
+
+Association	O
+Testing	O
+of	O
+HLA	O
+-	O
+DRB1	O
+and	O
+MHC	O
+Region	O
+SNPs	O
+
+In	O
+order	O
+to	O
+define	O
+the	O
+causal	O
+variation	O
+within	O
+the	O
+MHC	O
+region	O
+,	O
+we	O
+typed	O
+314	O
+complete	O
+SLE	O
+trios	O
+for	O
+the	O
+HLA	O
+-	O
+DRB1	O
+gene	O
+as	O
+well	O
+as	O
+for	O
+86	O
+SNPs	O
+across	O
+a	O
+2	O
+.	O
+4	O
+Mb	O
+region	O
+encompassing	O
+the	O
+HLA	O
+class	O
+I	O
+locus	O
+HLA	O
+-	O
+B	O
+to	O
+HLA	O
+-	O
+DPB2	O
+.	O
+
+High	O
+-	O
+quality	O
+genotype	O
+data	O
+was	O
+obtained	O
+for	O
+HLA	O
+-	O
+DRB1	O
+and	O
+68	O
+MHC	O
+SNPs	O
+(	O
+see	O
+Table	O
+S1	O
+for	O
+quality	O
+control	O
+data	O
+)	O
+.	O
+
+Association	O
+testing	O
+of	O
+the	O
+HLA	O
+-	O
+DRB1	O
+gene	O
+revealed	O
+a	O
+significant	O
+association	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+(	O
+nominal	O
+p	O
+=	O
+4	O
+.	O
+9	O
+x	O
+10	O
+-	O
+8	O
+,	O
+permuted	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+,	O
+T	O
+:	O
+U	O
+=	O
+129	O
+:	O
+55	O
+)	O
+in	O
+our	O
+lupus	O
+cohort	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+There	O
+was	O
+also	O
+a	O
+trend	O
+for	O
+under	O
+transmission	O
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+the	O
+HLA	O
+-	O
+DRB1	O
+*	O
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+(	O
+nominal	O
+p	O
+=	O
+0	O
+.	O
+0013	O
+,	O
+T	O
+:	O
+U	O
+42	O
+:	O
+77	O
+)	O
+;	O
+however	O
+,	O
+this	O
+association	O
+was	O
+no	O
+longer	O
+significant	O
+after	O
+correction	O
+for	O
+multiple	O
+testing	O
+as	O
+determined	O
+by	O
+10	O
+,	O
+000	O
+permutations	O
+of	O
+the	O
+dataset	O
+(	O
+permuted	O
+p	O
+=	O
+0	O
+.	O
+09	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+did	O
+not	O
+find	O
+evidence	O
+of	O
+association	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+(	O
+nominal	O
+p	O
+=	O
+1	O
+.	O
+0	O
+,	O
+T	O
+:	O
+U	O
+70	O
+:	O
+70	O
+)	O
+or	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0801	O
+(	O
+nominal	O
+p	O
+=	O
+1	O
+.	O
+0	O
+,	O
+T	O
+:	O
+U	O
+=	O
+11	O
+:	O
+11	O
+)	O
+in	O
+our	O
+cohort	O
+(	O
+see	O
+Table	O
+S2	O
+for	O
+complete	O
+HLA	O
+-	O
+DRB1	O
+association	O
+data	O
+)	O
+;	O
+alleles	O
+previously	O
+suggested	O
+by	O
+microsatellite	O
+typing	O
+of	O
+a	O
+US	O
+lupus	O
+cohort	O
+[	O
+25	O
+]	O
+.	O
+
+Association	O
+testing	O
+of	O
+the	O
+MHC	O
+region	O
+SNPs	O
+also	O
+identified	O
+significant	O
+evidence	O
+of	O
+association	O
+to	O
+SLE	O
+(	O
+Table	O
+1	O
+for	O
+associated	O
+markers	O
+and	O
+Table	O
+S3	O
+for	O
+all	O
+MHC	O
+SNPs	O
+)	O
+.	O
+
+The	O
+SNP	O
+with	O
+the	O
+most	O
+significant	O
+association	O
+,	O
+rs419788	O
+(	O
+nominal	O
+p	O
+=	O
+4	O
+.	O
+3	O
+x	O
+10	O
+-	O
+8	O
+,	O
+permuted	O
+p	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+was	O
+of	O
+similar	O
+strength	O
+to	O
+that	O
+of	O
+the	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+allele	O
+,	O
+with	O
+odds	O
+ratios	O
+(	O
+ORs	O
+)	O
+and	O
+95	O
+%	O
+confidence	O
+intervals	O
+(	O
+CIs	O
+)	O
+of	O
+2	O
+.	O
+0	O
+(	O
+1	O
+.	O
+6	O
+-	O
+2	O
+.	O
+6	O
+)	O
+and	O
+2	O
+.	O
+3	O
+(	O
+1	O
+.	O
+7	O
+-	O
+3	O
+.	O
+2	O
+)	O
+,	O
+respectively	O
+.	O
+
+This	O
+SNP	O
+is	O
+located	O
+within	O
+intron	O
+6	O
+of	O
+the	O
+class	O
+III	O
+gene	O
+,	O
+superkiller	O
+viralicidic	O
+activity	O
+2	O
+-	O
+like	O
+(	O
+Saccharomyces	B
+cerevisiae	I
+)	O
+(	O
+SKIV2L	O
+)	O
+,	O
+and	O
+is	O
+located	O
+approximately	O
+500	O
+kb	O
+telomeric	O
+to	O
+the	O
+HLA	O
+-	O
+DRB1	O
+gene	O
+.	O
+
+Of	O
+the	O
+other	O
+12	O
+SNPs	O
+that	O
+were	O
+significantly	O
+associated	O
+with	O
+SLE	O
+(	O
+nominal	O
+p	O
+=	O
+4	O
+.	O
+0	O
+x	O
+10	O
+-	O
+4	O
+to	O
+2	O
+.	O
+5	O
+x	O
+10	O
+-	O
+7	O
+;	O
+permuted	O
+p	O
+=	O
+0	O
+.	O
+03	O
+to	O
+<	O
+0	O
+.	O
+0001	O
+)	O
+,	O
+one	O
+was	O
+located	O
+in	O
+the	O
+class	O
+I	O
+region	O
+between	O
+HLA	O
+-	O
+B	O
+and	O
+MICA	O
+,	O
+seven	O
+were	O
+located	O
+in	O
+the	O
+class	O
+III	O
+region	O
+,	O
+and	O
+four	O
+were	O
+situated	O
+in	O
+the	O
+class	O
+II	O
+region	O
+(	O
+Table	O
+1	O
+;	O
+Figure	O
+S1	O
+)	O
+.	O
+
+Specifically	O
+,	O
+the	O
+seven	O
+associated	O
+class	O
+III	O
+SNPs	O
+were	O
+located	O
+in	O
+or	O
+close	O
+to	O
+the	O
+following	O
+genes	O
+:	O
+the	O
+TNF	O
+promoter	O
+,	O
+BAT3	O
+,	O
+SLC44A4	O
+,	O
+EHMT2	O
+,	O
+TNXB	O
+,	O
+GPSM3	O
+,	O
+and	O
+NOTCH4	O
+.	O
+
+One	O
+of	O
+the	O
+four	O
+class	O
+II	O
+associated	O
+SNPs	O
+was	O
+close	O
+to	O
+HLA	O
+-	O
+DRA	O
+,	O
+two	O
+were	O
+between	O
+HLA	O
+-	O
+DRB1	O
+and	O
+HLA	O
+-	O
+DQA1	O
+and	O
+one	O
+was	O
+in	O
+intron	O
+1	O
+of	O
+HLA	O
+-	O
+DQA1	O
+.	O
+
+The	O
+correlation	O
+between	O
+all	O
+68	O
+SNPs	O
+and	O
+HLA	O
+-	O
+DRB1	O
+in	O
+our	O
+UK	O
+SLE	O
+cohort	O
+is	O
+illustrated	O
+in	O
+Figure	O
+1	O
+.	O
+
+The	O
+markers	O
+showing	O
+significant	O
+association	O
+are	O
+highlighted	O
+.	O
+
+Conditional	O
+Analyses	O
+Identify	O
+Two	O
+Independent	O
+Association	O
+Signals	O
+in	O
+the	O
+MHC	O
+
+In	O
+order	O
+to	O
+establish	O
+whether	O
+the	O
+two	O
+most	O
+associated	O
+signals	O
+identified	O
+in	O
+this	O
+association	O
+-	O
+mapping	O
+experiment	O
+are	O
+likely	O
+to	O
+represent	O
+a	O
+single	O
+causal	O
+allele	O
+or	O
+independent	O
+risk	O
+factors	O
+,	O
+we	O
+first	O
+examined	O
+the	O
+association	O
+data	O
+conditioned	O
+upon	O
+the	O
+presence	O
+of	O
+the	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+allele	O
+.	O
+
+We	O
+found	O
+that	O
+four	O
+of	O
+the	O
+13	O
+associated	O
+SNPs	O
+showed	O
+evidence	O
+of	O
+signals	O
+independent	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+in	O
+our	O
+dataset	O
+,	O
+the	O
+strongest	O
+of	O
+which	O
+was	O
+rs419788	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+We	O
+therefore	O
+conditioned	O
+the	O
+three	O
+remaining	O
+SNPs	O
+(	O
+rs2523589	O
+,	O
+rs1052486	O
+,	O
+and	O
+rs605203	O
+)	O
+on	O
+rs419788	O
+to	O
+assess	O
+whether	O
+these	O
+signals	O
+are	O
+truly	O
+independent	O
+of	O
+each	O
+other	O
+or	O
+show	O
+association	O
+due	O
+to	O
+LD	O
+with	O
+rs419788	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+included	O
+HLA	O
+-	O
+DRB1	O
+in	O
+stepwise	O
+conditional	O
+regression	O
+analyses	O
+performed	O
+on	O
+the	O
+SNPs	O
+showing	O
+association	O
+independent	O
+of	O
+HLA	O
+-	O
+DRB1	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+These	O
+analyses	O
+demonstrated	O
+that	O
+the	O
+observed	O
+association	O
+signals	O
+at	O
+rs2523589	O
+,	O
+rs1052486	O
+,	O
+and	O
+rs605203	O
+were	O
+predominantly	O
+dependent	O
+upon	O
+the	O
+association	O
+at	O
+rs419788	O
+,	O
+and	O
+suggested	O
+that	O
+there	O
+are	O
+two	O
+major	O
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+association	O
+signals	O
+in	O
+the	O
+MHC	O
+in	O
+UK	O
+SLE	O
+:	O
+HLA	O
+-	O
+DRB1	O
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+rs419788	O
+.	O
+
+The	O
+independence	O
+of	O
+the	O
+association	O
+signals	O
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+HLA	O
+-	O
+DRB1	O
+and	O
+rs419788	O
+is	O
+further	O
+supported	O
+by	O
+the	O
+observation	O
+that	O
+there	O
+is	O
+only	O
+modest	O
+LD	O
+between	O
+these	O
+two	O
+(	O
+r2	O
+=	O
+0	O
+.	O
+24	O
+)	O
+.	O
+
+There	O
+was	O
+no	O
+association	O
+with	O
+any	O
+other	O
+HLA	O
+-	O
+DRB1	O
+allele	O
+and	O
+the	O
+four	O
+SNPs	O
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+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+(	O
+TRANSMIT	O
+,	O
+unpublished	O
+data	O
+)	O
+.	O
+
+The	O
+association	O
+of	O
+the	O
+tumour	O
+necrosis	O
+factor	O
+gene	O
+promoter	O
+SNP	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+with	O
+SLE	O
+is	O
+lost	O
+after	O
+conditioning	O
+for	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+in	O
+our	O
+cohort	O
+.	O
+
+If	O
+we	O
+perform	O
+the	O
+reverse	O
+analysis	O
+and	O
+condition	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+on	O
+the	O
+presence	O
+of	O
+the	O
+TNF	O
+promoter	O
+SNP	O
+,	O
+we	O
+find	O
+that	O
+the	O
+association	O
+remains	O
+,	O
+confirming	O
+that	O
+our	O
+TNF	O
+association	O
+is	O
+secondary	O
+to	O
+that	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+.	O
+
+Genotypic	O
+Risk	O
+for	O
+Class	O
+II	O
+and	O
+Class	O
+III	O
+Association	O
+Signals	O
+
+Having	O
+established	O
+independent	O
+association	O
+at	O
+the	O
+allelic	O
+level	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+and	O
+rs419788	O
+-	O
+T	O
+in	O
+our	O
+UK	O
+SLE	O
+cohort	O
+,	O
+we	O
+wanted	O
+to	O
+further	O
+determine	O
+the	O
+genotypic	O
+risk	O
+conferred	O
+by	O
+these	O
+variants	O
+and	O
+hence	O
+gain	O
+insight	O
+into	O
+their	O
+underlying	O
+mode	O
+of	O
+inheritance	O
+in	O
+lupus	O
+.	O
+
+We	O
+used	O
+case	O
+-	O
+control	O
+and	O
+family	O
+-	O
+based	O
+analyses	O
+to	O
+assess	O
+genotypic	O
+risk	O
+at	O
+HLA	O
+-	O
+DRB1	O
+,	O
+while	O
+the	O
+family	O
+-	O
+based	O
+test	O
+alone	O
+was	O
+used	O
+for	O
+rs419788	O
+.	O
+
+Common	O
+family	O
+-	O
+based	O
+tests	O
+of	O
+LD	O
+,	O
+such	O
+as	O
+those	O
+used	O
+in	O
+this	O
+study	O
+(	O
+Genehunter	O
+)	O
+,	O
+measure	O
+transmission	O
+distortion	O
+based	O
+on	O
+allele	O
+counts	O
+rather	O
+than	O
+genotype	O
+counts	O
+;	O
+the	O
+former	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+more	O
+powerful	O
+under	O
+additive	O
+models	O
+,	O
+while	O
+the	O
+latter	O
+has	O
+greater	O
+power	O
+under	O
+recessive	O
+or	O
+dominant	O
+genetic	O
+models	O
+[	O
+27	O
+]	O
+.	O
+
+The	O
+genotype	O
+-	O
+pedigree	O
+disequilibrium	O
+test	O
+(	O
+geno	O
+-	O
+PDT	O
+)	O
+determines	O
+LD	O
+between	O
+a	O
+locus	O
+genotype	O
+and	O
+disease	O
+by	O
+comparing	O
+genotypes	O
+that	O
+are	O
+transmitted	O
+from	O
+parent	O
+to	O
+proband	O
+with	O
+those	O
+that	O
+are	O
+not	O
+[	O
+27	O
+]	O
+.	O
+
+We	O
+used	O
+the	O
+geno	O
+-	O
+PDT	O
+to	O
+assess	O
+genotypic	O
+risk	O
+for	O
+our	O
+class	O
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+:	O
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+-	O
+DRB1	O
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+.	O
+
+In	O
+the	O
+case	O
+-	O
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+analysis	O
+for	O
+HLA	O
+-	O
+DRB1	O
+,	O
+ORs	O
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+95	O
+%	O
+CI	O
+were	O
+calculated	O
+and	O
+Fisher	O
+'	O
+s	O
+exact	O
+test	O
+employed	O
+to	O
+assess	O
+statistically	O
+significant	O
+differences	O
+between	O
+HLA	O
+-	O
+DRB1	O
+genotypes	O
+in	O
+lupus	O
+probands	O
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+healthy	O
+controls	O
+.	O
+
+For	O
+HLA	O
+-	O
+DRB1	O
+,	O
+the	O
+alleles	O
+were	O
+coded	O
+as	O
+follows	O
+:	O
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+-	O
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+*	O
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+,	O
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+-	O
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+,	O
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+-	O
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+*	O
+X	O
+where	O
+X	O
+represents	O
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+-	O
+DRB1	O
+alleles	O
+other	O
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+-	O
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+,	O
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+HLA	O
+-	O
+DRB1	O
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+.	O
+
+We	O
+included	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+in	O
+the	O
+analysis	O
+,	O
+even	O
+though	O
+we	O
+find	O
+no	O
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+association	O
+in	O
+our	O
+cohort	O
+,	O
+because	O
+previous	O
+studies	O
+have	O
+shown	O
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+greater	O
+risk	O
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+lupus	O
+in	O
+individuals	O
+who	O
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+-	O
+DRB1	O
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+-	O
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+-	O
+DRB1	O
+*	O
+1501	O
+-	O
+containing	O
+haplotypes	O
+[	O
+25	O
+,	O
+28	O
+]	O
+.	O
+
+Overall	O
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+results	O
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+-	O
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+0301	O
+(	O
+Table	O
+2	O
+)	O
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+dose	O
+-	O
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+(	O
+additive	O
+)	O
+effect	O
+from	O
+rs419788	O
+-	O
+T	O
+(	O
+Table	O
+3	O
+)	O
+.	O
+
+Specifically	O
+,	O
+both	O
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+-	O
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+geno	O
+-	O
+PDT	O
+demonstrate	O
+that	O
+there	O
+is	O
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+dose	O
+-	O
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+increase	O
+in	O
+disease	O
+risk	O
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+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+.	O
+
+Rather	O
+,	O
+it	O
+appears	O
+that	O
+the	O
+presence	O
+of	O
+a	O
+single	O
+copy	O
+of	O
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+-	O
+DRB1	O
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+alone	O
+is	O
+sufficient	O
+to	O
+increase	O
+susceptibility	O
+to	O
+disease	O
+.	O
+
+Moreover	O
+the	O
+0301	O
+/	O
+X	O
+genotypes	O
+constitute	O
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+our	O
+cohort	O
+rather	O
+than	O
+the	O
+0301	O
+/	O
+1501	O
+heterozygotes	O
+.	O
+
+Genotypes	O
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+-	O
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+absence	O
+of	O
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+-	O
+DRB1	O
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+revealed	O
+no	O
+significant	O
+association	O
+in	O
+our	O
+cohort	O
+.	O
+
+All	O
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+demonstrated	O
+significant	O
+association	O
+in	O
+our	O
+lupus	O
+families	O
+(	O
+Table	O
+3	O
+)	O
+.	O
+
+The	O
+common	O
+CC	O
+genotype	O
+was	O
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+transmitted	O
+,	O
+while	O
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+rare	O
+T	O
+allele	O
+displayed	O
+dose	O
+-	O
+dependent	O
+over	O
+transmission	O
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+lupus	O
+probands	O
+.	O
+
+Characterization	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+Risk	O
+Haplotype	O
+
+Next	O
+,	O
+we	O
+wanted	O
+to	O
+further	O
+delimit	O
+the	O
+MHC	O
+class	O
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+association	O
+signal	O
+that	O
+we	O
+have	O
+detected	O
+at	O
+HLA	O
+-	O
+DRB1	O
+.	O
+
+We	O
+used	O
+phased	O
+parental	O
+genotype	O
+data	O
+to	O
+compare	O
+the	O
+allelic	O
+composition	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+bearing	O
+haplotypes	O
+that	O
+were	O
+transmitted	O
+(	O
+T	O
+)	O
+to	O
+affected	O
+probands	O
+to	O
+those	O
+that	O
+were	O
+not	O
+transmitted	O
+(	O
+or	O
+untransmitted	O
+,	O
+UT	O
+)	O
+with	O
+the	O
+aim	O
+of	O
+identifying	O
+differences	O
+that	O
+could	O
+delineate	O
+the	O
+lupus	O
+susceptibility	O
+interval	O
+(	O
+s	O
+)	O
+arising	O
+from	O
+this	O
+haplotype	O
+(	O
+summarized	O
+in	O
+Figures	O
+2A	O
+,	O
+2B	O
+,	O
+and	O
+S2	O
+)	O
+.	O
+
+We	O
+observed	O
+a	O
+striking	O
+difference	O
+between	O
+transmitted	O
+and	O
+untransmitted	O
+chromosomes	O
+within	O
+the	O
+class	O
+II	O
+region	O
+:	O
+nearly	O
+all	O
+transmitted	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+haplotypes	O
+(	O
+99	O
+%	O
+)	O
+are	O
+identical	O
+across	O
+a	O
+180	O
+kb	O
+region	O
+defined	O
+by	O
+eight	O
+SNPs	O
+,	O
+whereas	O
+the	O
+corresponding	O
+region	O
+within	O
+untransmitted	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+haplotypes	O
+exhibits	O
+significant	O
+recombination	O
+.	O
+
+These	O
+data	O
+strongly	O
+suggest	O
+the	O
+existence	O
+of	O
+a	O
+risk	O
+haplotype	O
+that	O
+,	O
+interestingly	O
+,	O
+contains	O
+only	O
+three	O
+expressed	O
+genes	O
+:	O
+HLA	O
+-	O
+DRB1	O
+,	O
+HLA	O
+-	O
+DQA1	O
+,	O
+and	O
+HLA	O
+-	O
+DQB1	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+can	O
+confidently	O
+define	O
+the	O
+allelic	O
+composition	O
+of	O
+this	O
+risk	O
+haplotype	O
+,	O
+as	O
+these	O
+three	O
+genes	O
+are	O
+in	O
+strong	O
+LD	O
+and	O
+occur	O
+in	O
+one	O
+common	O
+haplotype	O
+in	O
+Caucasians	O
+:	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+HLA	O
+-	O
+DQA1	O
+*	O
+0501	O
+-	O
+HLA	O
+-	O
+DQB1	O
+*	O
+0201	O
+.	O
+
+Thus	O
+,	O
+we	O
+hypothesize	O
+that	O
+the	O
+specific	O
+combination	O
+of	O
+all	O
+three	O
+alleles	O
+is	O
+required	O
+to	O
+confer	O
+disease	O
+risk	O
+in	O
+lupus	O
+or	O
+that	O
+disease	O
+susceptibility	O
+lies	O
+with	O
+either	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+or	O
+the	O
+HLA	O
+-	O
+DQ	O
+alleles	O
+.	O
+
+We	O
+do	O
+not	O
+have	O
+sufficient	O
+numbers	O
+of	O
+recombinant	O
+chromosomes	O
+in	O
+this	O
+risk	O
+region	O
+to	O
+further	O
+delimit	O
+this	O
+signal	O
+:	O
+2	O
+/	O
+176	O
+(	O
+1	O
+.	O
+1	O
+%	O
+)	O
+transmitted	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+haplotypes	O
+are	O
+recombinant	O
+at	O
+HLA	O
+-	O
+DQA1	O
+-	O
+HLA	O
+-	O
+DQB1	O
+;	O
+3	O
+/	O
+178	O
+(	O
+1	O
+.	O
+7	O
+%	O
+)	O
+transmitted	O
+haplotypes	O
+identical	O
+across	O
+HLA	O
+-	O
+DQA1	O
+-	O
+HLA	O
+-	O
+DQB1	O
+do	O
+not	O
+possess	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+.	O
+
+The	O
+composite	O
+relative	O
+extended	O
+haplotype	O
+homozygosity	O
+(	O
+REHH	O
+)	O
+versus	O
+frequency	O
+plot	O
+for	O
+UK	O
+SLE	O
+;	O
+Utah	O
+residents	O
+with	O
+ancestry	O
+from	O
+northern	O
+and	O
+western	O
+Europe	O
+(	O
+CEPH	O
+)	O
+;	O
+and	O
+Yoruba	O
+in	O
+Ibadan	O
+,	O
+Nigeria	O
+(	O
+Yoruba	O
+)	O
+populations	O
+is	O
+shown	O
+in	O
+Figure	O
+3A	O
+.	O
+
+We	O
+can	O
+only	O
+comment	O
+on	O
+evidence	O
+for	O
+positive	O
+selection	O
+in	O
+CEPH	O
+individuals	O
+,	O
+as	O
+we	O
+have	O
+used	O
+this	O
+population	O
+alone	O
+to	O
+assess	O
+background	O
+variation	O
+on	O
+Chromosome	O
+6	O
+.	O
+
+The	O
+SLE	O
+and	O
+Yoruba	O
+cohorts	O
+are	O
+shown	O
+for	O
+comparative	O
+purposes	O
+.	O
+
+We	O
+find	O
+no	O
+evidence	O
+of	O
+positive	O
+selection	O
+for	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+in	O
+the	O
+CEPH	O
+population	O
+.	O
+
+However	O
+,	O
+this	O
+allele	O
+is	O
+enriched	O
+in	O
+our	O
+lupus	O
+cohort	O
+(	O
+21	O
+%	O
+of	O
+parental	O
+chromosomes	O
+)	O
+and	O
+displays	O
+greater	O
+extended	O
+homozygosity	O
+when	O
+compared	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+bearing	O
+haplotypes	O
+in	O
+CEPH	O
+and	O
+Yoruba	O
+.	O
+
+Hence	O
+,	O
+the	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+allele	O
+in	O
+lupus	O
+is	O
+observed	O
+as	O
+an	O
+outlier	O
+on	O
+the	O
+plot	O
+when	O
+compared	O
+to	O
+background	O
+variation	O
+in	O
+CEPH	O
+.	O
+
+These	O
+data	O
+support	O
+our	O
+previous	O
+observations	O
+(	O
+outlined	O
+above	O
+)	O
+of	O
+the	O
+highly	O
+conserved	O
+nature	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+haplotypes	O
+in	O
+lupus	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+haplotype	O
+bifurcation	O
+plots	O
+centered	O
+on	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+for	O
+UK	O
+SLE	O
+,	O
+CEPH	O
+,	O
+and	O
+Yoruba	O
+populations	O
+in	O
+Figure	O
+3B	O
+illustrate	O
+preservation	O
+of	O
+the	O
+common	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+haplotype	O
+in	O
+CEPH	O
+and	O
+UK	O
+SLE	O
+,	O
+while	O
+that	O
+seen	O
+in	O
+the	O
+Yoruba	O
+is	O
+significantly	O
+different	O
+.	O
+
+The	O
+class	O
+II	O
+regions	O
+of	O
+all	O
+three	O
+populations	O
+are	O
+essentially	O
+identical	O
+across	O
+our	O
+chosen	O
+SNPs	O
+;	O
+the	O
+main	O
+differences	O
+lie	O
+in	O
+class	O
+III	O
+.	O
+
+The	O
+difference	O
+in	O
+African	O
+populations	O
+in	O
+the	O
+class	O
+III	O
+region	O
+is	O
+one	O
+possible	O
+explanation	O
+for	O
+the	O
+lack	O
+of	O
+evidence	O
+for	O
+an	O
+association	O
+between	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+and	O
+SLE	O
+in	O
+African	O
+or	O
+African	O
+American	O
+populations	O
+.	O
+
+However	O
+,	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+has	O
+a	O
+lower	O
+frequency	O
+(	O
+~	O
+7	O
+%	O
+-	O
+10	O
+%	O
+)	O
+in	O
+African	O
+populations	O
+compared	O
+with	O
+Europeans	O
+(	O
+~	O
+13	O
+%	O
+)	O
+,	O
+and	O
+the	O
+number	O
+of	O
+HLA	O
+association	O
+studies	O
+conducted	O
+in	O
+African	O
+populations	O
+is	O
+very	O
+limited	O
+.	O
+
+Characterization	O
+of	O
+Class	O
+III	O
+Region	O
+Risk	O
+Haplotype	O
+
+Our	O
+data	O
+reveal	O
+a	O
+second	O
+independent	O
+signal	O
+at	O
+the	O
+MHC	O
+in	O
+SLE	O
+arising	O
+from	O
+the	O
+T	O
+allele	O
+of	O
+SNP	O
+rs419788	O
+in	O
+intron	O
+6	O
+of	O
+the	O
+class	O
+III	O
+gene	O
+,	O
+SKIV2L	O
+.	O
+
+Further	O
+evidence	O
+supporting	O
+the	O
+independence	O
+of	O
+the	O
+rs419788	O
+-	O
+T	O
+and	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+alleles	O
+is	O
+provided	O
+by	O
+the	O
+moderate	O
+LD	O
+between	O
+these	O
+two	O
+variants	O
+(	O
+r2	O
+=	O
+0	O
+.	O
+24	O
+)	O
+coupled	O
+with	O
+our	O
+data	O
+demonstrating	O
+that	O
+only	O
+47	O
+%	O
+of	O
+rs419788	O
+-	O
+T	O
+allele	O
+-	O
+bearing	O
+haplotypes	O
+contain	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+.	O
+
+The	O
+structure	O
+and	O
+composition	O
+of	O
+T	O
+and	O
+UT	O
+haplotypes	O
+anchored	O
+at	O
+rs419788	O
+-	O
+T	O
+were	O
+essentially	O
+identical	O
+(	O
+Figures	O
+2C	O
+,	O
+2D	O
+,	O
+and	O
+S2	O
+)	O
+,	O
+and	O
+hence	O
+not	O
+informative	O
+in	O
+delimiting	O
+our	O
+class	O
+III	O
+signal	O
+.	O
+
+Therefore	O
+,	O
+we	O
+examined	O
+the	O
+LD	O
+structure	O
+around	O
+our	O
+associated	O
+class	O
+III	O
+SNP	O
+to	O
+better	O
+define	O
+our	O
+disease	O
+risk	O
+interval	O
+.	O
+
+In	O
+our	O
+lupus	O
+dataset	O
+the	O
+rs419788	O
+-	O
+T	O
+allele	O
+resides	O
+on	O
+three	O
+of	O
+seven	O
+haplotypes	O
+present	O
+within	O
+a	O
+large	O
+block	O
+of	O
+six	O
+SNPs	O
+exhibiting	O
+strong	O
+LD	O
+.	O
+
+This	O
+haplotype	O
+block	O
+encompasses	O
+roughly	O
+270	O
+kb	O
+containing	O
+class	O
+III	O
+genes	O
+from	O
+SLC44A4	O
+to	O
+AGER	O
+,	O
+including	O
+the	O
+RCCX	O
+module	O
+.	O
+
+Next	O
+,	O
+we	O
+analyzed	O
+the	O
+haplotype	O
+block	O
+structure	O
+of	O
+this	O
+region	O
+in	O
+CEPH	O
+families	O
+using	O
+SNP	O
+data	O
+dumped	O
+from	O
+the	O
+International	O
+HapMap	O
+Project	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+hapmap	O
+.	O
+org	O
+/	O
+)	O
+.	O
+
+The	O
+greater	O
+density	O
+of	O
+SNP	O
+typing	O
+available	O
+in	O
+the	O
+HapMap	O
+CEPH	O
+population	O
+compared	O
+to	O
+our	O
+current	O
+UK	O
+SLE	O
+map	O
+allowed	O
+us	O
+to	O
+potentially	O
+refine	O
+our	O
+signal	O
+by	O
+exploring	O
+correlations	O
+between	O
+our	O
+associated	O
+SNP	O
+and	O
+those	O
+surrounding	O
+it	O
+.	O
+
+Analysis	O
+of	O
+these	O
+data	O
+(	O
+Figure	O
+4	O
+)	O
+suggests	O
+the	O
+presence	O
+of	O
+short	O
+-	O
+range	O
+LD	O
+around	O
+our	O
+associated	O
+variant	O
+,	O
+rs419788	O
+,	O
+in	O
+CEPH	O
+families	O
+,	O
+encompassing	O
+approximately	O
+40	O
+kb	O
+of	O
+the	O
+genome	O
+which	O
+includes	O
+the	O
+five	O
+genes	O
+:	O
+complement	O
+factor	O
+B	O
+(	O
+CFB	O
+)	O
+,	O
+RD	O
+RNA	O
+binding	O
+protein	O
+(	O
+RDBP	O
+)	O
+,	O
+SKIV2L	O
+,	O
+dom	O
+-	O
+3	O
+homolg	O
+Z	O
+(	O
+C	B
+.	I
+elegans	I
+)	O
+(	O
+DOM3Z	O
+)	O
+,	O
+and	O
+serine	O
+/	O
+threonine	O
+kinase	O
+19	O
+(	O
+STK19	O
+)	O
+,	O
+and	O
+does	O
+not	O
+include	O
+the	O
+complement	O
+C4	O
+locus	O
+.	O
+
+Furthermore	O
+,	O
+assessment	O
+of	O
+marker	O
+association	O
+in	O
+our	O
+lupus	O
+dataset	O
+demonstrates	O
+that	O
+after	O
+conditioning	O
+for	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+,	O
+the	O
+only	O
+markers	O
+that	O
+retain	O
+association	O
+signals	O
+are	O
+telomeric	O
+of	O
+SKIV2L	O
+,	O
+suggesting	O
+that	O
+complement	O
+C4	O
+,	O
+which	O
+is	O
+centromeric	O
+to	O
+this	O
+gene	O
+,	O
+may	O
+not	O
+be	O
+responsible	O
+for	O
+our	O
+independent	O
+class	O
+III	O
+signal	O
+.	O
+
+Subphenotype	O
+Analysis	O
+
+In	O
+order	O
+to	O
+gain	O
+further	O
+insight	O
+into	O
+disease	O
+pathogenesis	O
+,	O
+we	O
+examined	O
+common	O
+lupus	O
+subphenotypes	O
+.	O
+
+Such	O
+subsets	O
+are	O
+more	O
+homogeneous	O
+than	O
+lupus	O
+per	O
+se	O
+and	O
+thus	O
+maybe	O
+enriched	O
+for	O
+specific	O
+predisposing	O
+variants	O
+.	O
+
+In	O
+addition	O
+,	O
+one	O
+might	O
+expect	O
+a	O
+close	O
+association	O
+between	O
+MHC	O
+class	O
+II	O
+alleles	O
+and	O
+autoantibody	O
+subsets	O
+in	O
+lupus	O
+if	O
+these	O
+are	O
+indeed	O
+causal	O
+variants	O
+,	O
+given	O
+their	O
+role	O
+in	O
+antigen	O
+presentation	O
+and	O
+subsequent	O
+humoral	O
+immunity	O
+.	O
+
+We	O
+therefore	O
+tested	O
+our	O
+two	O
+main	O
+MHC	O
+association	O
+signals	O
+,	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+and	O
+rs419788	O
+,	O
+for	O
+association	O
+with	O
+renal	O
+disease	O
+and	O
+autoantibody	O
+subsets	O
+in	O
+our	O
+lupus	O
+cohort	O
+.	O
+
+We	O
+found	O
+that	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+was	O
+associated	O
+with	O
+the	O
+presence	O
+of	O
+anti	O
+-	O
+Ro	O
+and	O
+anti	O
+-	O
+La	O
+antibodies	O
+in	O
+our	O
+UK	O
+SLE	O
+cohort	O
+,	O
+with	O
+the	O
+latter	O
+showing	O
+the	O
+greatest	O
+evidence	O
+of	O
+association	O
+(	O
+anti	O
+-	O
+La	O
+nominal	O
+p	O
+<	O
+0	O
+.	O
+001	O
+compared	O
+with	O
+anti	O
+-	O
+Ro	O
+nominal	O
+p	O
+<	O
+0	O
+.	O
+025	O
+)	O
+.	O
+
+We	O
+found	O
+no	O
+association	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+with	O
+renal	O
+disease	O
+or	O
+any	O
+other	O
+autoantibody	O
+subsets	O
+in	O
+our	O
+dataset	O
+(	O
+see	O
+Table	O
+S4	O
+for	O
+detailed	O
+results	O
+)	O
+.	O
+
+Genotypes	O
+of	O
+the	O
+SNP	O
+rs419788	O
+were	O
+not	O
+associated	O
+with	O
+any	O
+of	O
+the	O
+tested	O
+lupus	O
+subphenotypes	O
+after	O
+controlling	O
+for	O
+the	O
+effect	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+Discussion	O
+
+We	O
+present	O
+the	O
+first	O
+family	O
+-	O
+based	O
+SNP	O
+association	O
+study	O
+of	O
+the	O
+MHC	O
+in	O
+SLE	O
+.	O
+
+We	O
+have	O
+genotyped	O
+69	O
+markers	O
+(	O
+HLA	O
+-	O
+DRB1	O
+and	O
+68	O
+SNPs	O
+)	O
+across	O
+2	O
+.	O
+4	O
+Mb	O
+of	O
+the	O
+MHC	O
+,	O
+encompassing	O
+class	O
+III	O
+and	O
+class	O
+II	O
+,	O
+in	O
+a	O
+cohort	O
+of	O
+314	O
+UK	O
+Caucasian	O
+SLE	O
+trios	O
+.	O
+
+Transmission	O
+disequilibrium	O
+testing	O
+of	O
+these	O
+data	O
+has	O
+shown	O
+predominant	O
+association	O
+with	O
+the	O
+alleles	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+and	O
+rs419788	O
+-	O
+T	O
+,	O
+together	O
+with	O
+12	O
+other	O
+MHC	O
+SNPs	O
+.	O
+
+Moreover	O
+,	O
+using	O
+conditional	O
+analyses	O
+,	O
+we	O
+have	O
+shown	O
+that	O
+the	O
+two	O
+primary	O
+signals	O
+of	O
+association	O
+at	O
+the	O
+MHC	O
+are	O
+independent	O
+of	O
+each	O
+other	O
+.	O
+
+Specifically	O
+,	O
+one	O
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+arises	O
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+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+in	O
+class	O
+II	O
+and	O
+the	O
+other	O
+from	O
+the	O
+T	O
+allele	O
+of	O
+SNP	O
+rs419788	O
+in	O
+the	O
+class	O
+III	O
+gene	O
+SKIV2L	O
+.	O
+
+Examination	O
+of	O
+bifurcation	O
+plots	O
+for	O
+T	O
+and	O
+UT	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+containing	O
+haplotypes	O
+has	O
+enabled	O
+delineation	O
+of	O
+our	O
+class	O
+II	O
+association	O
+signal	O
+to	O
+a	O
+180	O
+kb	O
+region	O
+encompassing	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+HLA	O
+-	O
+DQA1	O
+*	O
+0501	O
+-	O
+HLA	O
+-	O
+DQB1	O
+*	O
+0201	O
+.	O
+
+These	O
+data	O
+substantially	O
+refine	O
+that	O
+previously	O
+published	O
+by	O
+Graham	O
+et	O
+al	O
+.	O
+in	O
+2002	O
+[	O
+25	O
+]	O
+,	O
+where	O
+the	O
+lupus	O
+susceptibility	O
+interval	O
+within	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+containing	O
+haplotypes	O
+could	O
+only	O
+be	O
+delimited	O
+to	O
+a	O
+1	O
+Mb	O
+region	O
+encompassing	O
+class	O
+II	O
+and	O
+class	O
+III	O
+.	O
+
+The	O
+precise	O
+causal	O
+variant	O
+(	O
+s	O
+)	O
+within	O
+this	O
+region	O
+remains	O
+to	O
+be	O
+determined	O
+,	O
+as	O
+the	O
+three	O
+implicated	O
+alleles	O
+exhibit	O
+strong	O
+LD	O
+with	O
+few	O
+recombination	O
+events	O
+separating	O
+them	O
+(	O
+two	O
+out	O
+of	O
+176	O
+transmitted	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+chromosomes	O
+in	O
+our	O
+dataset	O
+)	O
+.	O
+
+However	O
+,	O
+all	O
+three	O
+allelic	O
+variants	O
+represent	O
+attractive	O
+functional	O
+candidates	O
+in	O
+lupus	O
+susceptibility	O
+for	O
+their	O
+role	O
+in	O
+antigen	O
+presentation	O
+and	O
+stimulation	O
+of	O
+the	O
+adaptive	O
+immune	O
+response	O
+.	O
+
+Our	O
+association	O
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+-	O
+DRB1	O
+*	O
+0301	O
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+lupus	O
+concurs	O
+with	O
+published	O
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+Caucasian	O
+cohorts	O
+and	O
+is	O
+well	O
+established	O
+[	O
+16	O
+]	O
+.	O
+
+While	O
+our	O
+lack	O
+of	O
+association	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
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+-	O
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+consistent	O
+with	O
+previous	O
+data	O
+from	O
+the	O
+UK	O
+[	O
+29	O
+]	O
+,	O
+Spain	O
+[	O
+30	O
+]	O
+,	O
+the	O
+Netherlands	O
+[	O
+31	O
+]	O
+,	O
+Sweden	O
+[	O
+32	O
+]	O
+,	O
+Mexico	O
+[	O
+33	O
+]	O
+,	O
+and	O
+the	O
+US	O
+[	O
+34	O
+]	O
+,	O
+it	O
+conflicts	O
+with	O
+that	O
+of	O
+other	O
+US	O
+groups	O
+[	O
+25	O
+,	O
+35	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+we	O
+demonstrate	O
+a	O
+trend	O
+,	O
+though	O
+not	O
+statistically	O
+significant	O
+,	O
+for	O
+undertransmission	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0701	O
+-	O
+-	O
+a	O
+result	O
+also	O
+observed	O
+in	O
+prior	O
+UK	O
+and	O
+Canadian	O
+lupus	O
+studies	O
+[	O
+29	O
+,	O
+36	O
+]	O
+.	O
+
+Moreover	O
+,	O
+a	O
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+association	O
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+HLA	O
+-	O
+DRB1	O
+*	O
+0701	O
+has	O
+been	O
+reported	O
+in	O
+other	O
+autoimmune	O
+diseases	O
+including	O
+Graves	O
+disease	O
+[	O
+37	O
+,	O
+38	O
+]	O
+,	O
+type	O
+1	O
+diabetes	O
+[	O
+39	O
+]	O
+,	O
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+rheumatoid	O
+arthritis	O
+[	O
+40	O
+]	O
+.	O
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+It	O
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+Minnesota	O
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+)	O
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+probands	O
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+The	O
+reason	O
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+A	O
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+-	O
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+In	O
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+There	O
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+/	O
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+Differences	O
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+populations	O
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+
+From	O
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+,	O
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+,	O
+Chi	O
+square	O
+p	O
+value	O
+<	O
+0	O
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+)	O
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+We	O
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+Furthermore	O
+,	O
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+,	O
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+the	O
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+.	O
+
+It	O
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+shows	O
+greater	O
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+comparison	O
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+,	O
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+.	O
+
+Previous	O
+studies	O
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+demonstrated	O
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+lupus	O
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+individuals	O
+carrying	O
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+combinations	O
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+-	O
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+-	O
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+-	O
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+-	O
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+,	O
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+The	O
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+-	O
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+-	O
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+-	O
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+-	O
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+-	O
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+increasing	O
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+[	O
+25	O
+,	O
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+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
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+risk	O
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+classically	O
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+-	O
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+contrast	O
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+
+[	O
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+,	O
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+,	O
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+-	O
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+
+The	O
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+-	O
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+-	O
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+-	O
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+
+Specifically	O
+,	O
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+-	O
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+,	O
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+,	O
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+
+Thus	O
+,	O
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+,	O
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+,	O
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+-	O
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+.	O
+
+Such	O
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+-	O
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++	O
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+,	O
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+.	O
+
+The	O
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+,	O
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+,	O
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+
+Interestingly	O
+,	O
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+,	O
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+,	O
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+greater	O
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+.	O
+
+The	O
+different	O
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+class	O
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+evidence	O
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+.	O
+
+A	O
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+-	O
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+-	O
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+alleles	O
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+been	O
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+autoantibody	O
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+in	O
+ethnically	O
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+lupus	O
+.	O
+
+The	O
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+associations	O
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+anti	O
+-	O
+Ro	O
+and	O
+anti	O
+-	O
+La	O
+antibodies	O
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+HLA	O
+-	O
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+-	O
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+(	O
+HLA	O
+-	O
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+)	O
+,	O
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+LD	O
+[	O
+41	O
+-	O
+45	O
+]	O
+in	O
+case	O
+-	O
+control	O
+studies	O
+.	O
+
+Here	O
+,	O
+we	O
+confirm	O
+the	O
+association	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+with	O
+anti	O
+-	O
+Ro	O
+and	O
+anti	O
+-	O
+La	O
+antibody	O
+production	O
+in	O
+our	O
+family	O
+-	O
+based	O
+cohort	O
+.	O
+
+Examination	O
+of	O
+LD	O
+structure	O
+around	O
+our	O
+second	O
+independent	O
+association	O
+,	O
+rs419788	O
+-	O
+T	O
+in	O
+class	O
+III	O
+,	O
+coupled	O
+with	O
+the	O
+results	O
+of	O
+our	O
+conditional	O
+analysis	O
+,	O
+suggests	O
+that	O
+this	O
+signal	O
+could	O
+also	O
+be	O
+delimited	O
+to	O
+a	O
+relatively	O
+narrow	O
+genomic	O
+interval	O
+of	O
+about	O
+40	O
+kb	O
+given	O
+further	O
+SNP	O
+mapping	O
+in	O
+our	O
+cohort	O
+.	O
+
+This	O
+region	O
+includes	O
+the	O
+genes	O
+CFB	O
+,	O
+RDBP	O
+,	O
+SKIV2L	O
+,	O
+DOM3Z	O
+,	O
+and	O
+STK19	O
+,	O
+but	O
+does	O
+not	O
+include	O
+complement	O
+C4	O
+.	O
+
+Thus	O
+,	O
+complement	O
+C4	O
+null	O
+alleles	O
+,	O
+which	O
+have	O
+been	O
+implicated	O
+in	O
+lupus	O
+pathogenesis	O
+,	O
+may	O
+not	O
+be	O
+responsible	O
+for	O
+our	O
+class	O
+III	O
+signal	O
+.	O
+
+We	O
+conclude	O
+,	O
+therefore	O
+,	O
+that	O
+our	O
+family	O
+-	O
+based	O
+mapping	O
+study	O
+has	O
+potentially	O
+revealed	O
+a	O
+hitherto	O
+unknown	O
+lupus	O
+susceptibility	O
+interval	O
+in	O
+the	O
+class	O
+III	O
+region	O
+of	O
+the	O
+MHC	O
+.	O
+
+However	O
+,	O
+we	O
+cannot	O
+conclusively	O
+exclude	O
+association	O
+at	O
+complement	O
+C4	O
+/	O
+RCCX	O
+without	O
+direct	O
+determination	O
+of	O
+C4	O
+polymorphism	O
+/	O
+copy	O
+number	O
+in	O
+our	O
+cohort	O
+.	O
+
+With	O
+respect	O
+to	O
+the	O
+genes	O
+implicated	O
+in	O
+our	O
+study	O
+,	O
+CFB	O
+is	O
+a	O
+vital	O
+component	O
+of	O
+the	O
+alternate	O
+complement	O
+pathway	O
+and	O
+disregulation	O
+may	O
+clearly	O
+affect	O
+the	O
+inflammatory	O
+response	O
+[	O
+46	O
+]	O
+.	O
+
+RD	O
+and	O
+Skiv2l	O
+are	O
+proteins	O
+potentially	O
+involved	O
+in	O
+RNA	O
+processing	O
+.	O
+
+The	O
+RD	O
+protein	O
+forms	O
+part	O
+of	O
+a	O
+negative	O
+elongation	O
+factor	O
+(	O
+NELF	O
+)	O
+complex	O
+that	O
+represses	O
+RNA	O
+polymerase	O
+II	O
+transcript	O
+elongation	O
+,	O
+while	O
+Skiv2l	O
+is	O
+a	O
+DEAD	O
+box	O
+protein	O
+with	O
+possible	O
+function	O
+as	O
+an	O
+RNA	O
+helicase	O
+.	O
+
+The	O
+function	O
+of	O
+Dom3z	O
+is	O
+currently	O
+unknown	O
+,	O
+although	O
+the	O
+homologous	O
+yeast	B
+protein	O
+binds	O
+nuclear	O
+exoribonuclease	O
+.	O
+
+Moreover	O
+,	O
+its	O
+ubiquitous	O
+expression	O
+suggests	O
+a	O
+housekeeping	O
+role	O
+.	O
+
+STK19	O
+is	O
+a	O
+protein	O
+kinase	O
+of	O
+unknown	O
+function	O
+with	O
+primary	O
+nuclear	O
+localization	O
+[	O
+47	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+RDBP	O
+and	O
+SKIV2L	O
+are	O
+found	O
+to	O
+be	O
+highly	O
+expressed	O
+in	O
+T	O
+lymphocytes	O
+,	O
+B	O
+lymphocytes	O
+,	O
+and	O
+dendritic	O
+cells	O
+(	O
+SymAtlas	O
+,	O
+http	O
+:	O
+/	O
+/	O
+symatlas	O
+.	O
+gnf	O
+.	O
+org	O
+/	O
+SymAtlas	O
+/	O
+)	O
+.	O
+
+A	O
+number	O
+of	O
+studies	O
+have	O
+demonstrated	O
+conflicting	O
+evidence	O
+for	O
+and	O
+against	O
+association	O
+with	O
+various	O
+TNF	O
+locus	O
+polymorphisms	O
+in	O
+SLE	O
+[	O
+48	O
+]	O
+.	O
+
+A	O
+recent	O
+meta	O
+-	O
+analysis	O
+of	O
+the	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+promoter	O
+polymorphism	O
+in	O
+SLE	O
+[	O
+48	O
+]	O
+revealed	O
+evidence	O
+of	O
+association	O
+for	O
+the	O
+minor	O
+allele	O
+(	O
+A	O
+)	O
+in	O
+European	O
+populations	O
+;	O
+however	O
+,	O
+this	O
+study	O
+did	O
+not	O
+account	O
+for	O
+LD	O
+with	O
+class	O
+II	O
+alleles	O
+.	O
+
+On	O
+conditioning	O
+our	O
+dataset	O
+for	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+,	O
+we	O
+find	O
+that	O
+the	O
+TNF	O
+promoter	O
+signal	O
+is	O
+lost	O
+,	O
+suggesting	O
+that	O
+this	O
+association	O
+is	O
+not	O
+independent	O
+and	O
+is	O
+due	O
+to	O
+LD	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+(	O
+or	O
+another	O
+variant	O
+in	O
+LD	O
+with	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+)	O
+.	O
+
+In	O
+summary	O
+,	O
+we	O
+have	O
+found	O
+association	O
+with	O
+two	O
+distinct	O
+and	O
+independent	O
+variants	O
+within	O
+the	O
+class	O
+II	O
+(	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+)	O
+and	O
+class	O
+III	O
+(	O
+SKIV2L	O
+)	O
+regions	O
+of	O
+the	O
+MHC	O
+in	O
+UK	O
+SLE	O
+trios	O
+.	O
+
+We	O
+can	O
+delimit	O
+our	O
+class	O
+II	O
+signal	O
+in	O
+lupus	O
+to	O
+three	O
+genetic	O
+variants	O
+(	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+-	O
+HLA	O
+-	O
+DQA1	O
+*	O
+0501	O
+-	O
+HLA	O
+-	O
+DQB1	O
+*	O
+0201	O
+)	O
+that	O
+may	O
+confer	O
+disease	O
+risk	O
+in	O
+combination	O
+or	O
+as	O
+separate	O
+signals	O
+.	O
+
+Our	O
+class	O
+III	O
+signal	O
+importantly	O
+excludes	O
+independent	O
+association	O
+at	O
+the	O
+TNF	O
+promoter	O
+polymorphism	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+and	O
+potentially	O
+provides	O
+a	O
+novel	O
+locus	O
+for	O
+further	O
+study	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Study	O
+cohorts	O
+.	O
+
+SLE	O
+families	O
+.	O
+
+The	O
+cohort	O
+comprises	O
+314	O
+complete	O
+SLE	O
+trios	O
+(	O
+that	O
+is	O
+,	O
+mother	O
+,	O
+father	O
+,	O
+and	O
+affected	O
+lupus	O
+proband	O
+)	O
+collected	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+All	O
+study	O
+participants	B
+are	O
+European	O
+Caucasian	O
+on	O
+the	O
+basis	O
+of	O
+grandparental	O
+origin	O
+.	O
+
+All	O
+314	O
+lupus	O
+probands	O
+(	O
+288	O
+female	O
+,	O
+26	O
+male	O
+)	O
+fulfill	O
+the	O
+revised	O
+American	O
+College	O
+of	O
+Rheumatology	O
+(	O
+ACR	O
+)	O
+criteria	O
+for	O
+SLE	O
+[	O
+50	O
+]	O
+,	O
+36	O
+%	O
+of	O
+whom	O
+have	O
+a	O
+diagnosis	O
+of	O
+lupus	O
+nephritis	O
+.	O
+
+Written	O
+consent	O
+was	O
+obtained	O
+from	O
+all	O
+study	O
+participants	B
+and	O
+ethical	O
+approval	O
+for	O
+this	O
+study	O
+was	O
+obtained	O
+from	O
+the	O
+Multi	O
+-	O
+Centre	O
+Research	O
+Ethics	O
+Committee	O
+(	O
+MREC	O
+2	O
+June	O
+1998	O
+)	O
+.	O
+
+Healthy	O
+controls	O
+.	O
+
+The	O
+control	O
+population	O
+for	O
+the	O
+HLA	O
+-	O
+DRB1	O
+genotypic	O
+risk	O
+case	O
+-	O
+control	O
+analysis	O
+constitutes	O
+1	O
+,	O
+667	O
+healthy	O
+males	O
+of	O
+Northern	O
+European	O
+origin	O
+.	O
+
+The	O
+individuals	O
+are	O
+potential	O
+hematopoietic	O
+stem	O
+cell	O
+donors	O
+and	O
+were	O
+typed	O
+to	O
+four	O
+digits	O
+for	O
+HLA	O
+-	O
+DRB1	O
+at	O
+the	O
+Anthony	O
+Nolan	O
+Trust	O
+,	O
+UK	O
+for	O
+this	O
+purpose	O
+.	O
+
+The	O
+level	O
+of	O
+resolution	O
+used	O
+for	O
+the	O
+typing	O
+of	O
+HLA	O
+-	O
+DRB1	O
+*	O
+15	O
+alleles	O
+in	O
+these	O
+healthy	O
+controls	O
+resulted	O
+in	O
+the	O
+ambiguous	O
+allele	O
+string	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+/	O
+1502	O
+/	O
+1504	O
+/	O
+1506	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+the	O
+great	O
+majority	O
+are	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+.	O
+
+There	O
+is	O
+no	O
+gender	O
+bias	O
+in	O
+HLA	O
+-	O
+DRB1	O
+allele	O
+frequencies	O
+,	O
+so	O
+although	O
+we	O
+have	O
+used	O
+a	O
+male	O
+control	O
+cohort	O
+,	O
+the	O
+frequencies	O
+would	O
+be	O
+expected	O
+to	O
+be	O
+the	O
+same	O
+in	O
+a	O
+similar	O
+female	O
+cohort	O
+(	O
+Steven	O
+Marsh	O
+,	O
+personal	O
+communication	O
+)	O
+.	O
+
+SNP	O
+genotyping	O
+.	O
+
+Eighty	O
+-	O
+six	O
+SNPs	O
+were	O
+chosen	O
+for	O
+genotyping	O
+in	O
+our	O
+mapping	O
+study	O
+.	O
+
+Specifically	O
+,	O
+we	O
+selected	O
+40	O
+MHC	O
+class	O
+II	O
+and	O
+class	O
+III	O
+haplotype	O
+tagging	O
+SNPs	O
+from	O
+a	O
+preliminary	O
+MHC	O
+SNP	O
+map	O
+[	O
+51	O
+]	O
+that	O
+had	O
+previously	O
+shown	O
+robust	O
+genotyping	O
+efficacy	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+typed	O
+36	O
+MHC	O
+class	O
+II	O
+tag	O
+SNPs	O
+from	O
+a	O
+subsequent	O
+high	O
+-	O
+resolution	O
+MHC	O
+study	O
+[	O
+52	O
+]	O
+.	O
+
+We	O
+also	O
+included	O
+the	O
+TNF	O
+-	O
+308G	O
+/	O
+A	O
+promoter	O
+SNP	O
+,	O
+together	O
+with	O
+nine	O
+further	O
+SNPs	O
+in	O
+the	O
+region	O
+of	O
+HLA	O
+-	O
+B	O
+and	O
+MICA	O
+obtained	O
+from	O
+the	O
+database	O
+,	O
+dbSNP	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+ncbi	O
+.	O
+nlm	O
+.	O
+nih	O
+.	O
+gov	O
+/	O
+projects	O
+/	O
+SNP	O
+/	O
+)	O
+.	O
+
+The	O
+latter	O
+SNPs	O
+had	O
+not	O
+been	O
+well	O
+characterized	O
+.	O
+
+All	O
+variants	O
+were	O
+typed	O
+in	O
+the	O
+entire	O
+cohort	O
+(	O
+n	O
+=	O
+942	O
+)	O
+.	O
+
+The	O
+SNPs	O
+span	O
+approximately	O
+2	O
+.	O
+4	O
+Mb	O
+of	O
+the	O
+MHC	O
+from	O
+the	O
+class	O
+I	O
+gene	O
+,	O
+KIAA1949	O
+to	O
+the	O
+class	O
+II	O
+pseudogene	O
+,	O
+HLA	O
+-	O
+DPB2	O
+and	O
+thus	O
+encompass	O
+MHC	O
+class	O
+III	O
+and	O
+class	O
+II	O
+.	O
+
+SNP	O
+genotyping	O
+was	O
+performed	O
+at	O
+the	O
+Broad	O
+Institute	O
+of	O
+MIT	O
+and	O
+Harvard	O
+and	O
+at	O
+Imperial	O
+College	O
+London	O
+by	O
+matrix	O
+-	O
+assisted	O
+laser	O
+desorption	O
+/	O
+ionisation	O
+time	O
+-	O
+of	O
+-	O
+flight	O
+(	O
+MALDI	O
+-	O
+TOF	O
+)	O
+mass	O
+spectrometry	O
+using	O
+the	O
+Sequenom	O
+MassARRAY	O
+platform	O
+as	O
+previously	O
+described	O
+[	O
+53	O
+]	O
+.	O
+
+SNPs	O
+that	O
+failed	O
+Sequenom	O
+typing	O
+were	O
+retyped	O
+by	O
+KBiosciences	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+kbioscience	O
+.	O
+co	O
+.	O
+uk	O
+/	O
+)	O
+using	O
+their	O
+in	O
+-	O
+house	O
+SNP	O
+genotyping	O
+methodology	O
+,	O
+KASPar	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+kbioscience	O
+.	O
+co	O
+.	O
+uk	O
+/	O
+genotyping	O
+/	O
+index	O
+.	O
+htm	O
+)	O
+,	O
+a	O
+competitive	O
+allele	O
+-	O
+specific	O
+PCR	O
+technique	O
+.	O
+
+HLA	O
+-	O
+DRB1	O
+genotyping	O
+.	O
+
+HLA	O
+-	O
+DRB1	O
+typing	O
+was	O
+performed	O
+at	O
+the	O
+Anthony	O
+Nolan	O
+Trust	O
+,	O
+UK	O
+.	O
+
+All	O
+samples	O
+(	O
+n	O
+=	O
+942	O
+UK	O
+SLE	O
+trios	O
+and	O
+n	O
+=	O
+1	O
+,	O
+667	O
+controls	O
+)	O
+were	O
+genotyped	O
+using	O
+LABType	O
+SSO	O
+(	O
+sequence	O
+-	O
+specific	O
+oligonucleotide	O
+)	O
+typing	O
+technology	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+written	O
+recommendations	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+onelambda	O
+.	O
+com	O
+)	O
+.	O
+
+Briefly	O
+,	O
+a	O
+locus	O
+-	O
+specific	O
+biotinylated	O
+PCR	O
+amplicon	O
+is	O
+produced	O
+,	O
+denatured	O
+,	O
+and	O
+rehybridized	O
+to	O
+complementary	O
+oligonucleotide	O
+probes	O
+conjugated	O
+to	O
+fluorescently	O
+coded	O
+beads	O
+.	O
+
+The	O
+bound	O
+biotinylated	O
+PCR	O
+product	O
+can	O
+be	O
+detected	O
+using	O
+R	O
+-	O
+phycoerythrin	O
+-	O
+conjugated	O
+streptavidin	O
+.	O
+
+A	O
+flow	O
+analyzer	O
+identifies	O
+the	O
+fluorescent	O
+intensity	O
+of	O
+phycoerythrin	O
+on	O
+each	O
+bead	O
+.	O
+
+The	O
+assignment	O
+of	O
+HLA	O
+type	O
+is	O
+based	O
+on	O
+the	O
+reaction	O
+pattern	O
+compared	O
+to	O
+patterns	O
+associated	O
+with	O
+known	O
+sequences	O
+.	O
+
+High	O
+resolution	O
+testing	O
+was	O
+performed	O
+using	O
+the	O
+Dynal	O
+AllSet	O
++	O
+SSP	O
+(	O
+sequence	O
+-	O
+specific	O
+primers	O
+)	O
+DRB1	O
+assay	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+(	O
+Invitrogen	O
+)	O
+for	O
+SLE	O
+families	O
+only	O
+.	O
+
+The	O
+presence	O
+or	O
+absence	O
+of	O
+PCR	O
+amplification	O
+was	O
+detected	O
+in	O
+a	O
+gel	O
+electrophoresis	O
+step	O
+using	O
+visualization	O
+by	O
+ethidium	O
+bromide	O
+incorporation	O
+.	O
+
+Genotypes	O
+were	O
+determined	O
+using	O
+SSPTool	O
+software	O
+.	O
+
+Samples	O
+that	O
+could	O
+not	O
+be	O
+resolved	O
+to	O
+four	O
+digits	O
+using	O
+SSO	O
+and	O
+PCR	O
+-	O
+SSP	O
+were	O
+analyzed	O
+by	O
+DNA	O
+sequencing	O
+of	O
+exon	O
+2	O
+of	O
+HLA	O
+-	O
+DRB1	O
+.	O
+
+Primers	O
+,	O
+reagents	O
+,	O
+and	O
+protocols	O
+were	O
+provided	O
+by	O
+The	O
+Anthony	O
+Nolan	O
+Trust	O
+,	O
+UK	O
+(	O
+primer	O
+sequences	O
+are	O
+available	O
+on	O
+request	O
+)	O
+.	O
+
+Specific	O
+HLA	O
+-	O
+DRB1	O
+alleles	O
+were	O
+assigned	O
+by	O
+comparing	O
+the	O
+resultant	O
+sequence	O
+with	O
+reference	O
+sequence	O
+from	O
+the	O
+IMGT	O
+/	O
+HLA	O
+Database	O
+[	O
+54	O
+]	O
+.	O
+
+Data	O
+analysis	O
+.	O
+
+Mendelian	O
+inconsistencies	O
+were	O
+removed	O
+using	O
+PedCheck	O
+[	O
+55	O
+]	O
+.	O
+
+Families	O
+in	O
+which	O
+more	O
+than	O
+eight	O
+markers	O
+demonstrated	O
+Mendel	O
+errors	O
+were	O
+removed	O
+from	O
+further	O
+analysis	O
+.	O
+
+Markers	O
+with	O
+less	O
+than	O
+80	O
+%	O
+genotyping	O
+efficiency	O
+and	O
+markers	O
+where	O
+more	O
+than	O
+eight	O
+families	O
+showed	O
+Mendel	O
+errors	O
+were	O
+also	O
+excluded	O
+from	O
+analysis	O
+.	O
+
+Two	O
+markers	O
+located	O
+within	O
+the	O
+SLE	O
+associated	O
+class	O
+II	O
+region	O
+(	O
+rs2239802	O
+in	O
+intron	O
+4	O
+of	O
+HLA	O
+-	O
+DRA	O
+and	O
+rs6457594	O
+in	O
+the	O
+region	O
+between	O
+HLA	O
+-	O
+DRB9	O
+and	O
+HLA	O
+-	O
+DRB5	O
+)	O
+show	O
+deviation	O
+from	O
+Hardy	O
+-	O
+Weinberg	O
+equilibrium	O
+(	O
+HWE	O
+)	O
+,	O
+which	O
+may	O
+reflect	O
+an	O
+undetected	O
+SLE	O
+association	O
+or	O
+systematic	O
+genotyping	O
+error	O
+.	O
+
+HWE	O
+was	O
+assessed	O
+in	O
+parental	O
+samples	O
+in	O
+our	O
+cohort	O
+.	O
+
+There	O
+is	O
+currently	O
+no	O
+uniform	O
+opinion	O
+in	O
+the	O
+community	O
+regarding	O
+the	O
+inclusion	O
+or	O
+exclusion	O
+of	O
+SNPs	O
+that	O
+show	O
+deviation	O
+from	O
+HWE	O
+,	O
+hence	O
+we	O
+elected	O
+to	O
+include	O
+these	O
+markers	O
+in	O
+the	O
+final	O
+analysis	O
+.	O
+
+Sixty	O
+-	O
+eight	O
+out	O
+of	O
+the	O
+total	O
+86	O
+SNPs	O
+passed	O
+our	O
+quality	O
+-	O
+control	O
+measures	O
+(	O
+see	O
+Table	O
+S1	O
+for	O
+details	O
+)	O
+.	O
+
+In	O
+summary	O
+,	O
+one	O
+SNP	O
+was	O
+monomorphic	O
+in	O
+our	O
+dataset	O
+,	O
+four	O
+SNPs	O
+yielded	O
+low	O
+genotyping	O
+efficiency	O
+,	O
+and	O
+13	O
+SNPs	O
+were	O
+excluded	O
+for	O
+unacceptable	O
+Mendel	O
+error	O
+rate	O
+.	O
+
+The	O
+mean	O
+call	O
+rate	O
+for	O
+all	O
+markers	O
+post	O
+-	O
+quality	O
+control	O
+was	O
+94	O
+%	O
+(	O
+range	O
+83	O
+%	O
+to	O
+99	O
+%	O
+)	O
+.	O
+
+Family	O
+-	O
+based	O
+association	O
+testing	O
+was	O
+performed	O
+using	O
+Genehunter	O
+TDT	O
+(	O
+version	O
+2	O
+.	O
+1	O
+)	O
+[	O
+56	O
+]	O
+and	O
+TRANSMIT	O
+(	O
+version	O
+2	O
+.	O
+5	O
+)	O
+[	O
+57	O
+]	O
+.	O
+
+Haplotypes	O
+were	O
+constructed	O
+and	O
+permutation	O
+testing	O
+performed	O
+using	O
+Haploview	O
+(	O
+version	O
+3	O
+.	O
+32	O
+)	O
+[	O
+58	O
+]	O
+.	O
+
+Significance	O
+of	O
+association	O
+signals	O
+in	O
+all	O
+analyses	O
+was	O
+based	O
+on	O
+permutation	O
+testing	O
+(	O
+10	O
+,	O
+000	O
+permutations	O
+)	O
+.	O
+
+The	O
+data	O
+are	O
+represented	O
+both	O
+as	O
+nominal	O
+and	O
+permuted	O
+p	O
+values	O
+.	O
+
+ORs	O
+with	O
+95	O
+%	O
+CI	O
+for	O
+family	O
+-	O
+based	O
+analyses	O
+were	O
+calculated	O
+in	O
+PLINK	O
+(	O
+http	O
+:	O
+/	O
+/	O
+pngu	O
+.	O
+mgh	O
+.	O
+harvard	O
+.	O
+edu	O
+/	O
+purcell	O
+/	O
+plink	O
+/	O
+)	O
+[	O
+59	O
+]	O
+.	O
+
+Conditional	O
+regression	O
+analyses	O
+were	O
+undertaken	O
+using	O
+WHAP	O
+[	O
+60	O
+]	O
+.	O
+
+The	O
+geno	O
+-	O
+PDT	O
+was	O
+performed	O
+using	O
+PDT	O
+version	O
+5	O
+.	O
+1	O
+with	O
+default	O
+settings	O
+[	O
+27	O
+]	O
+.	O
+
+The	O
+HLA	O
+-	O
+DRB1	O
+alleles	O
+were	O
+coded	O
+into	O
+three	O
+groups	O
+for	O
+the	O
+geno	O
+-	O
+PDT	O
+and	O
+the	O
+case	O
+-	O
+control	O
+analysis	O
+:	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+,	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+and	O
+HLA	O
+-	O
+DRX	O
+where	O
+HLA	O
+-	O
+DRX	O
+includes	O
+all	O
+HLA	O
+-	O
+DRB1	O
+alleles	O
+other	O
+than	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+or	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+.	O
+
+The	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+code	O
+in	O
+the	O
+healthy	O
+controls	O
+represents	O
+the	O
+allele	O
+string	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+/	O
+1502	O
+/	O
+1504	O
+/	O
+1506	O
+,	O
+as	O
+described	O
+previously	O
+.	O
+
+The	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+code	O
+in	O
+the	O
+lupus	O
+probands	O
+represents	O
+the	O
+alleles	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1501	O
+(	O
+84	O
+out	O
+of	O
+91	O
+*	O
+1501	O
+and	O
+*	O
+1502	O
+alleles	O
+)	O
+and	O
+HLA	O
+-	O
+DRB1	O
+*	O
+1502	O
+(	O
+7	O
+/	O
+91	O
+*	O
+1501	O
+and	O
+*	O
+1502	O
+alleles	O
+)	O
+,	O
+as	O
+*	O
+1504	O
+and	O
+*	O
+1506	O
+were	O
+not	O
+present	O
+in	O
+this	O
+population	O
+.	O
+
+Fisher	O
+'	O
+s	O
+exact	O
+test	O
+was	O
+used	O
+to	O
+assess	O
+significance	O
+of	O
+association	O
+in	O
+the	O
+case	O
+-	O
+control	O
+analysis	O
+.	O
+
+Subphenotype	O
+analysis	O
+.	O
+
+We	O
+looked	O
+for	O
+association	O
+of	O
+the	O
+HLA	O
+-	O
+DRB1	O
+*	O
+0301	O
+allele	O
+with	O
+autoantibody	O
+subsets	O
+and	O
+renal	O
+disease	O
+in	O
+our	O
+cohort	O
+using	O
+the	O
+Chi	O
+-	O
+square	O
+test	O
+.	O
+
+We	O
+compared	O
+cases	O
+with	O
+and	O
+without	O
+the	O
+subphenotype	O
+of	O
+interest	O
+with	O
+DRB1	O
+*	O
+0301	O
+homozygosity	O
+,	O
+heterozygosity	O
+,	O
+combined	O
+homozygosity	O
+and	O
+heterozygosity	O
+,	O
+and	O
+non	O
+-	O
+DRB1	O
+*	O
+0301	O
+status	O
+.	O
+
+We	O
+performed	O
+the	O
+same	O
+analyses	O
+for	O
+homozygous	O
+and	O
+heterozygous	O
+genotypes	O
+of	O
+the	O
+associated	O
+SNP	O
+rs419788	O
+.	O
+
+The	O
+autoantibody	O
+subsets	O
+compared	O
+were	O
+anti	O
+-	O
+C1q	O
+,	O
+IgG	O
+,	O
+and	O
+IgM	O
+anti	O
+-	O
+cardiolipin	O
+antibodies	O
+(	O
+ACLG	O
+and	O
+ACLM	O
+)	O
+,	O
+anti	O
+-	O
+Ro	O
+,	O
+anti	O
+-	O
+La	O
+,	O
+anti	O
+-	O
+RNP	O
+,	O
+anti	O
+-	O
+Sm	O
+,	O
+and	O
+anti	O
+-	O
+dsDNA	O
+.	O
+
+Delineation	O
+of	O
+associated	O
+MHC	O
+haplotypes	O
+and	O
+evidence	O
+for	O
+positive	O
+selection	O
+.	O
+
+We	O
+looked	O
+for	O
+positively	O
+selected	O
+alleles	O
+in	O
+our	O
+dataset	O
+using	O
+the	O
+long	O
+-	O
+range	O
+haplotype	O
+test	O
+as	O
+measured	O
+by	O
+extended	O
+haplotype	O
+homozygosity	O
+(	O
+EHH	O
+)	O
+,	O
+previously	O
+described	O
+by	O
+Sabeti	O
+et	O
+al	O
+.	O
+
+[	O
+26	O
+]	O
+.	O
+
+Essentially	O
+,	O
+such	O
+an	O
+analysis	O
+allows	O
+assessment	O
+of	O
+positive	O
+selection	O
+by	O
+mining	O
+datasets	O
+for	O
+high	O
+frequency	O
+extended	O
+haplotypes	O
+in	O
+comparison	O
+to	O
+the	O
+other	O
+core	O
+haplotypes	O
+at	O
+a	O
+locus	O
+.	O
+
+EHH	O
+is	O
+defined	O
+as	O
+the	O
+probability	O
+that	O
+two	O
+randomly	O
+chosen	O
+chromosomes	O
+carrying	O
+the	O
+core	O
+haplotype	O
+of	O
+interest	O
+will	O
+be	O
+identical	O
+by	O
+descent	O
+(	O
+homozygosity	O
+at	O
+all	O
+SNPs	O
+)	O
+for	O
+the	O
+entire	O
+interval	O
+from	O
+the	O
+core	O
+to	O
+a	O
+distance	O
+x	O
+.	O
+
+The	O
+REHH	O
+is	O
+the	O
+ratio	O
+of	O
+the	O
+EHH	O
+on	O
+the	O
+tested	O
+core	O
+haplotype	O
+compared	O
+with	O
+the	O
+combined	O
+EHH	O
+of	O
+all	O
+the	O
+other	O
+core	O
+haplotypes	O
+at	O
+the	O
+region	O
+excluding	O
+the	O
+tested	O
+core	O
+;	O
+as	O
+such	O
+,	O
+REHH	O
+accounts	O
+for	O
+local	O
+variation	O
+in	O
+recombination	O
+rate	O
+while	O
+EHH	O
+does	O
+not	O
+[	O
+26	O
+]	O
+.	O
+
+The	O
+program	O
+emphase	O
+was	O
+employed	O
+to	O
+assign	O
+the	O
+phase	O
+of	O
+parental	O
+genotype	O
+data	O
+and	O
+reconstruct	O
+missing	O
+information	O
+.	O
+
+Emphase	O
+is	O
+a	O
+simple	O
+phaser	O
+similar	O
+to	O
+the	O
+phaser	O
+of	O
+Excoffier	O
+and	O
+Slatkin	O
+[	O
+61	O
+]	O
+.	O
+
+It	O
+is	O
+very	O
+fast	O
+,	O
+especially	O
+on	O
+large	O
+datasets	O
+,	O
+and	O
+sufficiently	O
+accurate	O
+for	O
+most	O
+genetic	O
+applications	O
+.	O
+
+EHH	O
+analysis	O
+was	O
+performed	O
+on	O
+the	O
+phased	O
+parental	O
+data	O
+using	O
+the	O
+software	O
+program	O
+SWEEP	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+broad	O
+.	O
+mit	O
+.	O
+edu	O
+/	O
+mpg	O
+/	O
+sweep	O
+/	O
+index	O
+.	O
+html	O
+)	O
+.	O
+
+Haplotype	O
+bifurcation	O
+plots	O
+.	O
+
+We	O
+represent	O
+the	O
+breakdown	O
+of	O
+LD	O
+on	O
+core	O
+haplotypes	O
+using	O
+haplotype	O
+bifurcation	O
+diagrams	O
+generated	O
+in	O
+the	O
+program	O
+TREE	O
+[	O
+62	O
+]	O
+(	O
+also	O
+explained	O
+in	O
+[	O
+52	O
+]	O
+)	O
+.	O
+
+REHH	O
+versus	O
+frequency	O
+plots	O
+.	O
+
+Fifty	O
+-	O
+three	O
+SNPs	O
+(	O
+identified	O
+in	O
+Figure	O
+1	O
+)	O
+are	O
+common	O
+to	O
+our	O
+dataset	O
+and	O
+the	O
+CEPH	O
+and	O
+Yoruba	O
+HapMap	O
+[	O
+63	O
+]	O
+populations	O
+.	O
+
+These	O
+three	O
+datasets	O
+,	O
+together	O
+with	O
+CEPH	O
+SNP	O
+data	O
+for	O
+Chromosome	O
+6	O
+in	O
+its	O
+entirety	O
+,	O
+were	O
+used	O
+to	O
+generate	O
+separate	O
+REHH	O
+versus	O
+frequency	O
+plots	O
+in	O
+SWEEP	O
+.	O
+
+The	O
+plots	O
+from	O
+the	O
+four	O
+cohorts	O
+were	O
+combined	O
+for	O
+visual	O
+,	O
+not	O
+statistical	O
+,	O
+comparison	O
+.	O
+
+Evidence	O
+for	O
+positive	O
+selection	O
+was	O
+quantitatively	O
+assessed	O
+in	O
+CEPH	O
+individuals	O
+,	O
+as	O
+this	O
+population	O
+alone	O
+was	O
+used	O
+to	O
+assess	O
+background	O
+variation	O
+on	O
+Chromosome	O
+6	O
+.	O
+
+The	O
+UK	O
+SLE	O
+and	O
+Yoruba	O
+cohort	O
+data	O
+are	O
+shown	O
+for	O
+comparison	O
+.	O
+
+The	O
+95th	O
+percentile	O
+based	O
+on	O
+total	O
+CEPH	O
+Chromosome	O
+6	O
+SNP	O
+data	O
+is	O
+shown	O
+.	O
+
+Supporting	O
+Information	O
+
+Accession	O
+Numbers	O
+
+The	O
+Online	O
+Mendelian	O
+Inheritance	O
+in	O
+Man	B
+(	O
+OMIM	O
+,	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+ncbi	O
+.	O
+nlm	O
+.	O
+nih	O
+.	O
+gov	O
+/	O
+sites	O
+/	O
+entrez	O
+?	O
+db	O
+=	O
+omim	O
+)	O
+accession	O
+numbers	O
+for	O
+the	O
+genes	O
+described	O
+in	O
+this	O
+study	O
+are	O
+as	O
+follows	O
+:	O
+AGER	O
+,	O
+600214	O
+;	O
+BAT3	O
+,	O
+142590	O
+;	O
+C4A	O
+,	O
+120810	O
+;	O
+C4B	O
+,	O
+120820	O
+;	O
+CFB	O
+,	O
+138470	O
+;	O
+DOM3Z	O
+,	O
+605996	O
+;	O
+DOM3Z	O
+,	O
+605996	O
+;	O
+EHMT2	O
+,	O
+604599	O
+;	O
+HLA	O
+-	O
+B	O
+,	O
+142830	O
+;	O
+HLA	O
+-	O
+DPB2	O
+,	O
+120290	O
+;	O
+HLA	O
+-	O
+DQA1	O
+,	O
+146880	O
+;	O
+HLA	O
+-	O
+DQB1	O
+,	O
+604305	O
+;	O
+HLA	O
+-	O
+DRA	O
+,	O
+142860	O
+;	O
+HLA	O
+-	O
+DRB1	O
+,	O
+142857	O
+;	O
+KIAA1949	O
+,	O
+610990	O
+;	O
+MICA	O
+,	O
+600169	O
+;	O
+NOTCH4	O
+,	O
+164951	O
+;	O
+RDBP	O
+,	O
+154040	O
+;	O
+RDBP	O
+,	O
+154040	O
+;	O
+SKIV2L	O
+,	O
+600478	O
+;	O
+SLC44A4	O
+,	O
+606107	O
+;	O
+STK19	O
+,	O
+604977	O
+;	O
+STK19	O
+,	O
+604977	O
+;	O
+TNF	O
+,	O
+191160	O
+;	O
+and	O
+TNXB	O
+,	O
+600985	O
+.	O
+
+SuperCAT	O
+:	O
+a	O
+supertree	O
+database	O
+for	O
+combined	O
+and	O
+integrative	O
+multilocus	O
+sequence	O
+typing	O
+analysis	O
+of	O
+the	O
+Bacillus	B
+cereus	I
+group	I
+of	O
+bacteria	O
+(	O
+including	O
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+,	O
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+.	I
+anthracis	I
+and	O
+B	B
+.	I
+thuringiensis	I
+)	O
+
+Abstract	O
+
+The	O
+Bacillus	B
+cereus	I
+group	I
+of	O
+bacteria	O
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+important	O
+group	O
+including	O
+mammalian	O
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+insect	O
+pathogens	O
+,	O
+such	O
+as	O
+B	B
+.	I
+anthracis	I
+,	O
+the	O
+anthrax	B
+bacterium	O
+,	O
+B	B
+.	I
+thuringiensis	I
+,	O
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+as	O
+a	O
+biological	O
+pesticide	O
+and	O
+B	B
+.	I
+cereus	I
+,	O
+often	O
+involved	O
+in	O
+food	O
+poisoning	O
+incidents	O
+.	O
+
+To	O
+characterize	O
+the	O
+population	O
+structure	O
+and	O
+epidemiology	O
+of	O
+these	O
+bacteria	O
+,	O
+five	O
+separate	O
+multilocus	O
+sequence	O
+typing	O
+(	O
+MLST	O
+)	O
+schemes	O
+have	O
+been	O
+developed	O
+,	O
+which	O
+makes	O
+results	O
+difficult	O
+to	O
+compare	O
+.	O
+
+Therefore	O
+,	O
+we	O
+have	O
+developed	O
+a	O
+database	O
+that	O
+compiles	O
+and	O
+integrates	O
+MLST	O
+data	O
+from	O
+all	O
+five	O
+schemes	O
+for	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+,	O
+accessible	O
+at	O
+http	O
+:	O
+/	O
+/	O
+mlstoslo	O
+.	O
+uio	O
+.	O
+no	O
+/	O
+.	O
+
+Supertree	O
+techniques	O
+were	O
+used	O
+to	O
+combine	O
+the	O
+phylogenetic	O
+information	O
+from	O
+analysis	O
+of	O
+all	O
+schemes	O
+and	O
+datasets	O
+,	O
+in	O
+order	O
+to	O
+produce	O
+an	O
+integrated	O
+view	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+population	O
+.	O
+
+The	O
+database	O
+currently	O
+contains	O
+strain	O
+information	O
+and	O
+sequence	O
+data	O
+for	O
+1029	O
+isolates	O
+and	O
+26	O
+housekeeping	O
+gene	O
+fragments	O
+,	O
+which	O
+can	O
+be	O
+searched	O
+by	O
+keywords	O
+,	O
+MLST	O
+scheme	O
+,	O
+or	O
+sequence	O
+similarity	O
+.	O
+
+Supertrees	O
+can	O
+be	O
+browsed	O
+according	O
+to	O
+various	O
+criteria	O
+such	O
+as	O
+species	O
+,	O
+isolate	O
+source	O
+,	O
+or	O
+genetic	O
+distance	O
+,	O
+and	O
+subtrees	O
+containing	O
+strains	O
+of	O
+interest	O
+can	O
+be	O
+extracted	O
+.	O
+
+Besides	O
+analysis	O
+of	O
+the	O
+available	O
+data	O
+,	O
+the	O
+user	O
+has	O
+the	O
+possibility	O
+to	O
+enter	O
+her	O
+/	O
+his	O
+own	O
+sequences	O
+and	O
+compare	O
+them	O
+to	O
+the	O
+database	O
+and	O
+/	O
+or	O
+include	O
+them	O
+into	O
+the	O
+supertree	O
+reconstructions	O
+.	O
+
+INTRODUCTION	O
+
+Multilocus	O
+sequence	O
+typing	O
+(	O
+MLST	O
+)	O
+is	O
+a	O
+tool	O
+that	O
+is	O
+widely	O
+used	O
+for	O
+phylogenetic	O
+typing	O
+of	O
+bacteria	O
+.	O
+
+MLST	O
+is	O
+based	O
+on	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+amplification	O
+and	O
+sequencing	O
+of	O
+internal	O
+fragments	O
+of	O
+usually	O
+seven	O
+essential	O
+or	O
+housekeeping	O
+genes	O
+spread	O
+around	O
+the	O
+bacterial	O
+chromosome	O
+.	O
+
+The	O
+genetic	O
+relatedness	O
+among	O
+isolates	O
+is	O
+then	O
+determined	O
+by	O
+comparison	O
+of	O
+the	O
+nucleotide	O
+sequence	O
+types	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+MLST	O
+is	O
+thus	O
+a	O
+method	O
+that	O
+is	O
+unambiguous	O
+and	O
+truly	O
+portable	O
+among	O
+laboratories	O
+.	O
+
+Since	O
+the	O
+initial	O
+development	O
+of	O
+this	O
+technique	O
+for	O
+Neisseria	B
+meningitidis	I
+in	O
+1998	O
+,	O
+MLST	O
+schemes	O
+have	O
+been	O
+developed	O
+for	O
+about	O
+30	O
+species	O
+including	O
+some	O
+of	O
+the	O
+most	O
+important	O
+bacterial	O
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+,	O
+e	O
+.	O
+g	O
+.	O
+Streptococcus	B
+pneumoniae	I
+,	O
+Streptococcus	B
+pyogenes	I
+,	O
+Haemophilus	B
+influenzae	I
+,	O
+Staphylococcus	B
+aureus	I
+,	O
+Campylobacter	B
+jejuni	I
+,	O
+Enterococcus	B
+faecium	I
+,	O
+Burkholderia	B
+pseudomallei	I
+,	O
+Escherichia	B
+coli	I
+,	O
+Salmonella	B
+enterica	I
+and	O
+the	O
+Bacillus	B
+cereus	I
+group	I
+(	O
+see	O
+(	O
+1	O
+)	O
+for	O
+a	O
+recent	O
+review	O
+)	O
+.	O
+
+These	O
+MLST	O
+schemes	O
+have	O
+been	O
+used	O
+successfully	O
+to	O
+explore	O
+the	O
+population	O
+structure	O
+of	O
+bacteria	O
+,	O
+to	O
+study	O
+the	O
+evolution	O
+of	O
+their	O
+virulence	O
+properties	O
+,	O
+to	O
+identify	O
+antibiotic	O
+-	O
+resistant	O
+strains	O
+and	O
+epidemic	O
+clones	O
+,	O
+and	O
+for	O
+epidemiological	O
+surveillance	O
+.	O
+
+The	O
+B	B
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+cereus	I
+group	I
+includes	O
+bacterial	O
+species	O
+that	O
+are	O
+of	O
+medical	O
+and	O
+/	O
+or	O
+economic	O
+importance	O
+,	O
+such	O
+as	O
+B	B
+.	I
+anthracis	I
+,	O
+an	O
+obligate	O
+mammalian	O
+pathogen	O
+causing	O
+the	O
+lethal	O
+disease	O
+anthrax	B
+,	O
+B	B
+.	I
+cereus	I
+,	O
+an	O
+opportunistic	O
+human	B
+pathogen	O
+involved	O
+in	O
+food	O
+-	O
+poisoning	O
+incidents	O
+and	O
+contaminations	O
+in	O
+hospitals	O
+,	O
+B	B
+.	I
+thuringiensis	I
+,	O
+an	O
+insect	O
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+and	O
+one	O
+of	O
+the	O
+world	O
+'	O
+s	O
+most	O
+widely	O
+used	O
+biopesticide	O
+and	O
+B	B
+.	I
+weihenstephanensis	I
+,	O
+a	O
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+-	O
+tolerant	O
+species	O
+known	O
+for	O
+contaminating	O
+dairies	O
+.	O
+
+These	O
+species	O
+are	O
+genetically	O
+very	O
+closely	O
+related	O
+and	O
+may	O
+be	O
+considered	O
+as	O
+one	O
+species	O
+based	O
+on	O
+genetic	O
+and	O
+genomic	O
+evidence	O
+(	O
+3	O
+-	O
+5	O
+)	O
+.	O
+
+Unlike	O
+other	O
+bacterial	O
+species	O
+that	O
+are	O
+typed	O
+using	O
+a	O
+single	O
+MLST	O
+scheme	O
+,	O
+five	O
+separate	O
+schemes	O
+have	O
+been	O
+developed	O
+for	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+,	O
+based	O
+on	O
+different	O
+sets	O
+of	O
+genes	O
+and	O
+isolates	O
+(	O
+5	O
+-	O
+10	O
+)	O
+.	O
+
+The	O
+Priest	O
+scheme	O
+(	O
+8	O
+)	O
+is	O
+currently	O
+the	O
+most	O
+widely	O
+used	O
+.	O
+
+Studies	O
+with	O
+the	O
+various	O
+schemes	O
+have	O
+independently	O
+indicated	O
+that	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+population	O
+is	O
+divided	O
+into	O
+three	O
+main	O
+phylogenetic	O
+clusters	O
+and	O
+that	O
+species	O
+are	O
+usually	O
+intermixed	O
+within	O
+the	O
+groups	O
+.	O
+
+One	O
+cluster	O
+contains	O
+the	O
+monomorphic	O
+B	B
+.	I
+anthracis	I
+isolates	O
+and	O
+a	O
+number	O
+of	O
+B	B
+.	I
+cereus	I
+and	O
+B	B
+.	I
+thuringiensis	I
+strains	O
+,	O
+many	O
+of	O
+which	O
+are	O
+from	O
+clinical	O
+sources	O
+.	O
+
+A	O
+second	O
+heterogeneous	O
+cluster	O
+includes	O
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+.	I
+cereus	I
+and	O
+B	B
+.	I
+thuringiensis	I
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+,	O
+while	O
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+-	O
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+and	O
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+.	I
+cereus	I
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+belong	O
+to	O
+the	O
+third	O
+group	O
+.	O
+
+The	O
+separate	O
+MLST	O
+analyses	O
+have	O
+also	O
+revealed	O
+that	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+population	O
+is	O
+weakly	O
+clonal	O
+overall	O
+due	O
+to	O
+numerous	O
+clinical	O
+and	O
+virulent	O
+isolates	O
+emerging	O
+from	O
+different	O
+phylogenetic	O
+positions	O
+(	O
+5	O
+-	O
+8	O
+,	O
+11	O
+-	O
+14	O
+)	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+the	O
+'	O
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+-	O
+tolerant	O
+'	O
+cluster	O
+that	O
+seems	O
+to	O
+exhibit	O
+a	O
+panmictic	O
+(	O
+or	O
+sexual	O
+)	O
+population	O
+structure	O
+,	O
+i	O
+.	O
+e	O
+.	O
+with	O
+frequent	O
+genetic	O
+exchanges	O
+between	O
+strains	O
+(	O
+9	O
+)	O
+.	O
+
+Despite	O
+the	O
+overall	O
+congruence	O
+between	O
+the	O
+various	O
+MLST	O
+studies	O
+,	O
+the	O
+use	O
+of	O
+separate	O
+schemes	O
+with	O
+no	O
+gene	O
+overlap	O
+and	O
+very	O
+little	O
+strain	O
+overlap	O
+has	O
+produced	O
+a	O
+confusing	O
+situation	O
+and	O
+makes	O
+the	O
+results	O
+difficult	O
+to	O
+compare	O
+directly	O
+.	O
+
+Therefore	O
+,	O
+we	O
+recently	O
+proposed	O
+a	O
+combined	O
+scheme	O
+based	O
+on	O
+genes	O
+taken	O
+from	O
+three	O
+of	O
+the	O
+four	O
+schemes	O
+available	O
+by	O
+then	O
+and	O
+for	O
+which	O
+we	O
+created	O
+a	O
+web	O
+-	O
+based	O
+database	O
+accessible	O
+at	O
+the	O
+University	O
+of	O
+Oslo	O
+'	O
+s	O
+MLST	O
+server	O
+,	O
+http	O
+:	O
+/	O
+/	O
+mlstoslo	O
+.	O
+uio	O
+.	O
+no	O
+/	O
+(	O
+5	O
+)	O
+.	O
+
+Here	O
+,	O
+in	O
+order	O
+to	O
+provide	O
+the	O
+B	B
+.	I
+cereus	I
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+research	O
+community	O
+with	O
+a	O
+common	O
+MLST	O
+resource	O
+,	O
+we	O
+have	O
+developed	O
+on	O
+the	O
+same	O
+website	O
+a	O
+database	O
+,	O
+SuperCAT	O
+,	O
+that	O
+compiles	O
+and	O
+integrates	O
+MLST	O
+data	O
+from	O
+all	O
+the	O
+published	O
+B	B
+.	I
+cereus	I
+group	I
+schemes	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+applied	O
+supertree	O
+reconstruction	O
+methods	O
+to	O
+build	O
+an	O
+integrated	O
+view	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+population	O
+and	O
+phylogeny	O
+.	O
+
+Below	O
+we	O
+describe	O
+the	O
+content	O
+and	O
+main	O
+features	O
+of	O
+the	O
+new	O
+database	O
+as	O
+well	O
+as	O
+the	O
+process	O
+of	O
+supertree	O
+building	O
+.	O
+
+DATABASE	O
+CONTENT	O
+AND	O
+IMPLEMENTATION	O
+
+The	O
+SuperCAT	O
+database	O
+provides	O
+information	O
+,	O
+sequence	O
+and	O
+phylogenetic	O
+data	O
+for	O
+all	O
+bacterial	O
+isolates	O
+that	O
+have	O
+been	O
+typed	O
+using	O
+any	O
+of	O
+the	O
+five	O
+published	O
+MLST	O
+schemes	O
+for	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Strain	O
+information	O
+,	O
+when	O
+known	O
+,	O
+includes	O
+isolate	O
+description	O
+,	O
+source	O
+and	O
+geographical	O
+location	O
+of	O
+isolation	O
+,	O
+and	O
+the	O
+scheme	O
+(	O
+s	O
+)	O
+used	O
+for	O
+typing	O
+.	O
+
+The	O
+sequence	O
+data	O
+include	O
+the	O
+nucleotide	O
+sequences	O
+of	O
+the	O
+MLST	O
+loci	O
+examined	O
+in	O
+a	O
+given	O
+strain	O
+.	O
+
+SuperCAT	O
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+contains	O
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+supertree	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
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+reconstructed	O
+by	O
+combining	O
+the	O
+sequence	O
+data	O
+from	O
+all	O
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+schemes	O
+,	O
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+well	O
+as	O
+supertrees	O
+built	O
+for	O
+individual	O
+schemes	O
+.	O
+
+Information	O
+and	O
+sequences	O
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+isolates	O
+typed	O
+by	O
+the	O
+Priest	O
+and	O
+Tourasse	O
+-	O
+Helgason	O
+schemes	O
+were	O
+retrieved	O
+from	O
+the	O
+databases	O
+devoted	O
+to	O
+these	O
+schemes	O
+at	O
+http	O
+:	O
+/	O
+/	O
+pubmlst	O
+.	O
+org	O
+/	O
+bcereus	O
+and	O
+http	O
+:	O
+/	O
+/	O
+mlstoslo	O
+.	O
+uio	O
+.	O
+no	O
+/	O
+,	O
+respectively	O
+.	O
+
+MLST	O
+data	O
+for	O
+additional	O
+strains	O
+not	O
+available	O
+in	O
+the	O
+pubmlst	O
+.	O
+org	O
+repository	O
+(	O
+strains	O
+from	O
+(	O
+15	O
+)	O
+are	O
+missing	O
+therein	O
+)	O
+and	O
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+the	O
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+,	O
+Ko	O
+,	O
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+Candelon	O
+-	O
+Sorokin	O
+schemes	O
+were	O
+taken	O
+from	O
+the	O
+published	O
+literature	O
+and	O
+the	O
+Genbank	O
+nucleotide	O
+sequence	O
+database	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+sequences	O
+of	O
+all	O
+MLST	O
+loci	O
+were	O
+extracted	O
+from	O
+the	O
+complete	O
+genomes	O
+of	O
+the	O
+21	O
+sequenced	O
+B	B
+.	I
+cereus	I
+group	I
+strains	O
+available	O
+in	O
+Genbank	O
+.	O
+
+Altogether	O
+,	O
+SuperCAT	O
+currently	O
+contains	O
+data	O
+for	O
+1029	O
+isolates	O
+and	O
+26	O
+gene	O
+fragments	O
+from	O
+25	O
+different	O
+genes	O
+.	O
+
+However	O
+,	O
+since	O
+most	O
+strains	O
+have	O
+been	O
+typed	O
+using	O
+only	O
+6	O
+or	O
+7	O
+of	O
+the	O
+26	O
+loci	O
+,	O
+about	O
+one	O
+-	O
+third	O
+of	O
+the	O
+complete	O
+set	O
+of	O
+sequences	O
+are	O
+included	O
+.	O
+
+The	O
+26	O
+loci	O
+,	O
+only	O
+available	O
+for	O
+the	O
+completely	O
+sequenced	O
+strains	O
+,	O
+sum	O
+up	O
+to	O
+10	O
+619	O
+bp	O
+.	O
+
+All	O
+these	O
+genes	O
+are	O
+located	O
+on	O
+the	O
+chromosome	O
+,	O
+thus	O
+the	O
+database	O
+provides	O
+no	O
+information	O
+about	O
+extrachromosomal	O
+plasmids	O
+even	O
+though	O
+most	O
+of	O
+the	O
+strains	O
+do	O
+carry	O
+one	O
+or	O
+several	O
+small	O
+and	O
+/	O
+or	O
+large	O
+plasmids	O
+.	O
+
+Unlike	O
+scheme	O
+-	O
+specific	O
+MLST	O
+databases	O
+,	O
+SuperCAT	O
+does	O
+not	O
+contain	O
+allele	O
+and	O
+sequence	O
+type	O
+(	O
+ST	O
+)	O
+numbers	O
+.	O
+
+Since	O
+isolates	O
+in	O
+SuperCAT	O
+have	O
+been	O
+typed	O
+by	O
+different	O
+subsets	O
+of	O
+loci	O
+,	O
+complete	O
+allelic	O
+profiles	O
+are	O
+unavailable	O
+and	O
+therefore	O
+STs	O
+cannot	O
+be	O
+assigned	O
+for	O
+most	O
+strains	O
+,	O
+except	O
+the	O
+fully	O
+sequenced	O
+ones	O
+.	O
+
+Table	O
+1	O
+.	O
+The	O
+five	O
+MLST	O
+schemes	O
+designed	O
+for	O
+typing	O
+bacteria	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
+groupSchemeGenesTota	I
+sequence	O
+length	O
+(	O
+bp	O
+)	O
+Total	O
+number	O
+of	O
+isolateseUsed	O
+in	O
+(	O
+references	O
+)	O
+Helgasonadk	O
+,	O
+ccpA	O
+,	O
+ftsA	O
+,	O
+glpT	O
+,	O
+pyre	O
+,	O
+recF	O
+and	O
+sucC2	O
+938120	O
+(	O
+6	O
+,	O
+12	O
+,	O
+46	O
+)	O
+Candelon	O
+-	O
+Sorokina	O
+,	O
+cclpC	O
+,	O
+dinB	O
+,	O
+gdpD	O
+,	O
+panC	O
+,	O
+purF	O
+and	O
+yhfL2	O
+850149	O
+(	O
+9	O
+,	O
+10	O
+)	O
+Kob	O
+,	O
+cgyrB	O
+,	O
+mbl	O
+,	O
+mdh	O
+,	O
+mutS	O
+,	O
+pycA	O
+(	O
+1	O
+)	O
+and	O
+rpoB2	O
+00265	O
+(	O
+7	O
+)	O
+Priesta	O
+,	O
+bglpF	O
+,	O
+gmk	O
+,	O
+ilvD	O
+,	O
+pta	O
+,	O
+purH	O
+,	O
+pycA	O
+(	O
+2	O
+)	O
+and	O
+tpi2	O
+829721	O
+(	O
+8	O
+,	O
+11	O
+,	O
+13	O
+-	O
+15	O
+,	O
+46	O
+-	O
+48	O
+)	O
+Tourasse	O
+-	O
+Helgasona	O
+,	O
+b	O
+,	O
+dadk	O
+,	O
+ccpA	O
+,	O
+glpF	O
+,	O
+glpT	O
+,	O
+panC	O
+,	O
+pta	O
+and	O
+pycA	O
+(	O
+2	O
+)	O
+2	O
+658172	O
+(	O
+5	O
+)	O
+aSpecific	O
+databases	O
+for	O
+the	O
+Priest	O
+and	O
+Tourasse	O
+-	O
+Helgason	O
+schemes	O
+are	O
+accessible	O
+at	O
+http	O
+:	O
+/	O
+/	O
+pubmlst	O
+.	O
+org	O
+/	O
+bcereus	O
+/	O
+and	O
+http	O
+:	O
+/	O
+/	O
+mlstoslo	O
+.	O
+uio	O
+.	O
+no	O
+/	O
+,	O
+respectively	O
+.	O
+
+A	O
+BLAST	O
+database	O
+for	O
+the	O
+Candelon	O
+-	O
+Sorokin	O
+scheme	O
+is	O
+available	O
+at	O
+http	O
+:	O
+/	O
+/	O
+spock	O
+.	O
+jouy	O
+.	O
+inra	O
+.	O
+fr	O
+/	O
+cgi	O
+-	O
+bin	O
+/	O
+bacilliMLSopen	O
+.	O
+cgi	O
+.	O
+bWhile	O
+the	O
+Tourasse	O
+-	O
+Helgason	O
+and	O
+Priest	O
+schemes	O
+use	O
+the	O
+same	O
+gene	O
+fragment	O
+for	O
+the	O
+pycA	O
+gene	O
+,	O
+the	O
+Ko	O
+scheme	O
+is	O
+based	O
+on	O
+a	O
+different	O
+and	O
+non	O
+-	O
+overlapping	O
+gene	O
+region	O
+.	O
+cThe	O
+B	B
+.	I
+cereus	I
+group	I
+-	O
+specific	O
+transcriptional	O
+regulator	O
+plcR	O
+was	O
+originally	O
+included	O
+in	O
+the	O
+Candelon	O
+-	O
+Sorokin	O
+and	O
+Ko	O
+schemes	O
+.	O
+
+However	O
+,	O
+plcR	O
+follows	O
+a	O
+phylogeny	O
+different	O
+from	O
+the	O
+other	O
+MLST	O
+loci	O
+(	O
+7	O
+,	O
+10	O
+)	O
+and	O
+is	O
+no	O
+longer	O
+used	O
+for	O
+MLST	O
+;	O
+therefore	O
+,	O
+it	O
+is	O
+not	O
+included	O
+in	O
+SuperCAT	O
+.	O
+dThe	O
+Tourasse	O
+-	O
+Helgason	O
+scheme	O
+is	O
+a	O
+combined	O
+scheme	O
+based	O
+on	O
+3	O
+genes	O
+from	O
+the	O
+Helgason	O
+scheme	O
+(	O
+adk	O
+,	O
+ccpA	O
+,	O
+and	O
+glpT	O
+)	O
+,	O
+3	O
+genes	O
+from	O
+the	O
+Priest	O
+scheme	O
+(	O
+glpF	O
+,	O
+pta	O
+and	O
+pycA	O
+(	O
+2	O
+)	O
+)	O
+,	O
+and	O
+the	O
+panC	O
+gene	O
+from	O
+the	O
+Candelon	O
+-	O
+Sorokin	O
+scheme	O
+.	O
+eIncluding	O
+strains	O
+with	O
+fully	O
+sequenced	O
+genomes	O
+.	O
+
+SuperCAT	O
+is	O
+built	O
+as	O
+a	O
+relational	O
+database	O
+using	O
+the	O
+PostgreSQL	O
+management	O
+system	O
+,	O
+and	O
+data	O
+are	O
+accessible	O
+through	O
+a	O
+graphical	O
+web	O
+interface	O
+.	O
+
+User	O
+queries	O
+and	O
+results	O
+pages	O
+are	O
+processed	O
+and	O
+created	O
+on	O
+-	O
+the	O
+-	O
+fly	O
+via	O
+a	O
+highly	O
+modified	O
+version	O
+of	O
+the	O
+mlstdbNet	O
+software	O
+(	O
+16	O
+)	O
+written	O
+in	O
+PERL	O
+and	O
+based	O
+on	O
+the	O
+DataBase	O
+Interface	O
+(	O
+DBI	O
+)	O
+and	O
+Common	O
+Gateway	O
+Interface	O
+(	O
+CGI	O
+)	O
+modules	O
+.	O
+
+The	O
+database	O
+is	O
+implemented	O
+on	O
+a	O
+Linux	O
+Apache	O
+web	O
+server	O
+maintained	O
+through	O
+the	O
+facilities	O
+and	O
+support	O
+provided	O
+by	O
+the	O
+Norwegian	O
+EMBnet	O
+node	O
+.	O
+
+Some	O
+large	O
+supertree	O
+computations	O
+are	O
+run	O
+on	O
+a	O
+Linux	O
+supercomputer	O
+at	O
+the	O
+University	O
+of	O
+Oslo	O
+.	O
+
+The	O
+ATV	O
+(	O
+A	O
+Tree	O
+Viewer	O
+)	O
+Java	O
+applet	O
+is	O
+used	O
+for	O
+phylogenetic	O
+tree	O
+display	O
+(	O
+17	O
+)	O
+.	O
+
+ATV	O
+notably	O
+supports	O
+horizontal	O
+and	O
+vertical	O
+zooming	O
+capabilities	O
+that	O
+are	O
+suitable	O
+for	O
+browsing	O
+large	O
+trees	O
+.	O
+
+The	O
+Jalview	O
+editor	O
+Java	O
+applet	O
+is	O
+also	O
+implemented	O
+in	O
+SuperCAT	O
+for	O
+advanced	O
+multiple	O
+sequence	O
+alignment	O
+display	O
+(	O
+18	O
+)	O
+.	O
+
+SUPERTREE	O
+RECONSTRUCTION	O
+
+Supertree	O
+techniques	O
+allow	O
+to	O
+combine	O
+the	O
+phylogenetic	O
+information	O
+from	O
+different	O
+datasets	O
+into	O
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+phylogenetic	O
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+studies	O
+have	O
+shown	O
+that	O
+meaningful	O
+supertrees	O
+can	O
+be	O
+obtained	O
+even	O
+when	O
+taxon	O
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+is	O
+very	O
+sparse	O
+(	O
+see	O
+(	O
+19	O
+,	O
+20	O
+)	O
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+reviews	O
+)	O
+.	O
+
+Supertree	O
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+has	O
+thus	O
+become	O
+increasingly	O
+popular	O
+for	O
+taking	O
+advantage	O
+and	O
+combining	O
+the	O
+massive	O
+amount	O
+of	O
+sequence	O
+data	O
+available	O
+in	O
+public	O
+databases	O
+for	O
+reconstructing	O
+large	O
+-	O
+scale	O
+organismal	O
+phylogenies	O
+with	O
+the	O
+ultimate	O
+goal	O
+of	O
+building	O
+the	O
+tree	O
+of	O
+life	O
+(	O
+21	O
+-	O
+24	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+the	O
+21	O
+B	B
+.	I
+cereus	I
+group	I
+strains	O
+that	O
+have	O
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+,	O
+and	O
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+which	O
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+sequences	O
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+all	O
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+MLST	O
+loci	O
+are	O
+thus	O
+available	O
+,	O
+can	O
+be	O
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+to	O
+join	O
+all	O
+five	O
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+provide	O
+the	O
+strain	O
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+necessary	O
+for	O
+supertree	O
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+.	O
+
+The	O
+global	O
+B	B
+.	I
+cereus	I
+group	I
+supertree	O
+,	O
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+1029	O
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+,	O
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+reconstructed	O
+according	O
+to	O
+the	O
+widely	O
+used	O
+matrix	O
+representation	O
+by	O
+parsimony	O
+(	O
+MRP	O
+)	O
+procedure	O
+(	O
+Figure	O
+1	O
+;	O
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+19	O
+,	O
+25	O
+,	O
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+)	O
+)	O
+.	O
+
+Scheme	O
+-	O
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+each	O
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+same	O
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+.	O
+
+Briefly	O
+,	O
+a	O
+phylogenetic	O
+tree	O
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+built	O
+for	O
+every	O
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+PHYML	O
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+program	O
+(	O
+27	O
+)	O
+.	O
+
+Then	O
+,	O
+each	O
+gene	O
+tree	O
+is	O
+recoded	O
+into	O
+a	O
+binary	O
+matrix	O
+representing	O
+the	O
+branching	O
+order	O
+(	O
+i	O
+.	O
+e	O
+.	O
+the	O
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+groupings	O
+)	O
+following	O
+standard	O
+MRP	O
+coding	O
+using	O
+the	O
+SuperMRP	O
+.	O
+pl	O
+script	O
+(	O
+28	O
+)	O
+.	O
+
+All	O
+gene	O
+tree	O
+matrices	O
+are	O
+concatenated	O
+into	O
+a	O
+supermatrix	O
+,	O
+in	O
+which	O
+isolates	O
+missing	O
+from	O
+a	O
+particular	O
+tree	O
+are	O
+coded	O
+using	O
+the	O
+'	O
+?	O
+'	O
+character	O
+representing	O
+unknown	O
+data	O
+.	O
+
+In	O
+this	O
+supermatrix	O
+,	O
+the	O
+sequence	O
+of	O
+0	O
+'	O
+s	O
+,	O
+1	O
+'	O
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+'	O
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+defines	O
+the	O
+branching	O
+profile	O
+of	O
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+strain	O
+.	O
+
+Closely	O
+related	O
+strains	O
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+similar	O
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+profiles	O
+.	O
+
+Supertrees	O
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+the	O
+program	O
+MIX	O
+from	O
+the	O
+PHYLIP	O
+package	O
+(	O
+29	O
+)	O
+run	O
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+.	O
+
+The	O
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+number	O
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+,	O
+where	O
+the	O
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+can	O
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+0	O
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+)	O
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+
+As	O
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+,	O
+the	O
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+.	O
+
+In	O
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+,	O
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+-	O
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+(	O
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+)	O
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+-	O
+Hasegawa	O
+-	O
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+(	O
+27	O
+,	O
+30	O
+)	O
+.	O
+
+aLRTs	O
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+requirement	O
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+like	O
+traditional	O
+bootstrap	O
+procedures	O
+.	O
+
+The	O
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+-	O
+1984	O
+nucleotide	O
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+supplemented	O
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+(	O
+F84	O
++	O
+Gamma	O
+)	O
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+(	O
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+)	O
+.	O
+
+This	O
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+,	O
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+/	O
+transversion	O
+rate	O
+bias	O
+,	O
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+-	O
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+rate	O
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+among	O
+sites	O
+.	O
+
+It	O
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+chosen	O
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+exploratory	O
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+ModelTest	O
+(	O
+32	O
+,	O
+33	O
+)	O
+,	O
+which	O
+indicated	O
+that	O
+models	O
+including	O
+these	O
+three	O
+factors	O
+were	O
+most	O
+appropriate	O
+for	O
+the	O
+MLST	O
+loci	O
+studied	O
+,	O
+although	O
+models	O
+for	O
+individual	O
+loci	O
+differed	O
+slightly	O
+.	O
+
+Note	O
+that	O
+the	O
+maximum	O
+likelihood	O
+technique	O
+also	O
+allows	O
+for	O
+uneven	O
+rates	O
+of	O
+nucleotide	O
+substitution	O
+between	O
+strains	O
+,	O
+which	O
+allows	O
+to	O
+accommodate	O
+slow	O
+-	O
+and	O
+fast	O
+-	O
+evolving	O
+isolates	O
+.	O
+
+To	O
+reduce	O
+the	O
+size	O
+of	O
+the	O
+binary	O
+supermatrix	O
+and	O
+speed	O
+up	O
+computations	O
+,	O
+individual	O
+gene	O
+trees	O
+and	O
+the	O
+supertree	O
+were	O
+built	O
+using	O
+only	O
+one	O
+representative	O
+from	O
+a	O
+set	O
+of	O
+strains	O
+having	O
+identical	O
+sequences	O
+.	O
+
+The	O
+remaining	O
+identical	O
+isolates	O
+were	O
+graphically	O
+added	O
+to	O
+the	O
+tree	O
+afterwards	O
+when	O
+drawing	O
+the	O
+final	O
+supertree	O
+.	O
+
+Figure	O
+1	O
+.	O
+Schematic	O
+overview	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+supertree	O
+reconstruction	O
+procedure	O
+using	O
+Matrix	O
+Representation	O
+by	O
+Parsimony	O
+(	O
+MRP	O
+)	O
+.	O
+
+See	O
+text	O
+for	O
+details	O
+.	O
+
+It	O
+should	O
+be	O
+noted	O
+that	O
+the	O
+global	O
+1029	O
+-	O
+strain	O
+supertree	O
+retains	O
+the	O
+phylogenetic	O
+signals	O
+from	O
+the	O
+individual	O
+schemes	O
+and	O
+contains	O
+the	O
+three	O
+main	O
+clusters	O
+of	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+population	O
+described	O
+in	O
+the	O
+section	O
+'	O
+Introduction	O
+'	O
+.	O
+
+The	O
+integrated	O
+SuperCAT	O
+system	O
+may	O
+also	O
+allow	O
+to	O
+infer	O
+new	O
+relationships	O
+between	O
+strains	O
+that	O
+were	O
+analyzed	O
+with	O
+different	O
+gene	O
+sets	O
+.	O
+
+Even	O
+though	O
+the	O
+26	O
+loci	O
+sequences	O
+are	O
+available	O
+for	O
+only	O
+21	O
+isolates	O
+,	O
+they	O
+apparently	O
+provide	O
+enough	O
+overlap	O
+information	O
+for	O
+building	O
+the	O
+main	O
+branches	O
+of	O
+the	O
+supertree	O
+.	O
+
+These	O
+21	O
+isolates	O
+cover	O
+all	O
+three	O
+clusters	O
+,	O
+although	O
+the	O
+majority	O
+of	O
+them	O
+are	O
+B	B
+.	I
+anthracis	I
+strains	O
+or	O
+clinical	O
+strains	O
+closely	O
+related	O
+to	O
+B	B
+.	I
+anthracis	I
+due	O
+to	O
+the	O
+focus	O
+of	O
+genome	O
+sequencing	O
+projects	O
+,	O
+making	O
+the	O
+part	O
+of	O
+the	O
+supertree	O
+containing	O
+these	O
+isolates	O
+likely	O
+to	O
+be	O
+more	O
+accurate	O
+than	O
+the	O
+rest	O
+of	O
+the	O
+tree	O
+.	O
+
+Furthermore	O
+,	O
+111	O
+other	O
+isolates	O
+have	O
+been	O
+typed	O
+by	O
+10	O
+genes	O
+or	O
+more	O
+,	O
+providing	O
+additional	O
+overlap	O
+(	O
+see	O
+the	O
+'	O
+Gene	O
+Distribution	O
+'	O
+page	O
+)	O
+.	O
+
+Although	O
+about	O
+two	O
+-	O
+thirds	O
+of	O
+the	O
+sequence	O
+data	O
+are	O
+missing	O
+overall	O
+,	O
+it	O
+has	O
+been	O
+shown	O
+for	O
+other	O
+organisms	O
+that	O
+relevant	O
+supertrees	O
+could	O
+be	O
+reconstructed	O
+with	O
+datasets	O
+containing	O
+more	O
+than	O
+90	O
+%	O
+of	O
+missing	O
+data	O
+,	O
+especially	O
+when	O
+the	O
+characters	O
+that	O
+are	O
+present	O
+are	O
+informative	O
+(	O
+20	O
+,	O
+22	O
+,	O
+23	O
+,	O
+34	O
+)	O
+.	O
+
+Empirical	O
+and	O
+simulation	O
+studies	O
+have	O
+indicated	O
+that	O
+this	O
+behavior	O
+may	O
+be	O
+due	O
+to	O
+the	O
+fact	O
+that	O
+the	O
+characters	O
+which	O
+are	O
+present	O
+are	O
+more	O
+important	O
+for	O
+the	O
+tree	O
+-	O
+building	O
+process	O
+than	O
+those	O
+which	O
+are	O
+absent	O
+(	O
+see	O
+(	O
+20	O
+,	O
+34	O
+)	O
+and	O
+references	O
+therein	O
+)	O
+.	O
+
+Precise	O
+within	O
+-	O
+cluster	O
+groupings	O
+may	O
+contain	O
+more	O
+uncertainty	O
+,	O
+as	O
+indicated	O
+by	O
+the	O
+large	O
+number	O
+of	O
+unresolved	O
+multifurcations	O
+in	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+supertree	O
+.	O
+
+Finally	O
+,	O
+it	O
+is	O
+also	O
+worth	O
+mentioning	O
+that	O
+the	O
+branching	O
+orders	O
+of	O
+the	O
+scheme	O
+-	O
+specific	O
+MRP	O
+supertrees	O
+are	O
+highly	O
+correlated	O
+to	O
+those	O
+of	O
+the	O
+published	O
+trees	O
+built	O
+with	O
+concatenated	O
+sequences	O
+and	O
+other	O
+phylogenetic	O
+algorithms	O
+.	O
+
+DATA	O
+ACCESS	O
+AND	O
+MANIPULATION	O
+
+The	O
+complete	O
+list	O
+of	O
+isolates	O
+included	O
+in	O
+SuperCAT	O
+(	O
+currently	O
+1029	O
+)	O
+with	O
+strain	O
+description	O
+,	O
+source	O
+and	O
+country	O
+of	O
+origin	O
+is	O
+available	O
+at	O
+the	O
+database	O
+home	O
+page	O
+.	O
+
+By	O
+default	O
+all	O
+isolates	O
+in	O
+the	O
+database	O
+are	O
+used	O
+in	O
+the	O
+analysis	O
+tools	O
+provided	O
+,	O
+but	O
+the	O
+user	O
+can	O
+select	O
+strains	O
+of	O
+interest	O
+by	O
+keywords	O
+,	O
+MLST	O
+scheme	O
+,	O
+entering	O
+a	O
+list	O
+of	O
+strain	O
+identifiers	O
+,	O
+or	O
+choosing	O
+isolates	O
+individually	O
+via	O
+checkboxes	O
+.	O
+
+All	O
+subsequent	O
+analyses	O
+will	O
+be	O
+based	O
+on	O
+the	O
+selected	O
+strain	O
+subset	O
+and	O
+their	O
+loci	O
+.	O
+
+The	O
+keyword	O
+search	O
+will	O
+look	O
+for	O
+matches	O
+in	O
+any	O
+of	O
+the	O
+strain	O
+,	O
+description	O
+,	O
+source	O
+,	O
+location	O
+and	O
+scheme	O
+fields	O
+.	O
+
+Complex	O
+keyword	O
+queries	O
+with	O
+several	O
+logical	O
+operators	O
+can	O
+be	O
+formulated	O
+in	O
+the	O
+'	O
+advanced	O
+search	O
+'	O
+page	O
+.	O
+
+Note	O
+that	O
+many	O
+isolates	O
+were	O
+referred	O
+by	O
+alternative	O
+names	O
+in	O
+different	O
+MLST	O
+schemes	O
+and	O
+publications	O
+,	O
+therefore	O
+synonyms	O
+have	O
+been	O
+included	O
+in	O
+the	O
+strain	O
+descriptions	O
+that	O
+allow	O
+a	O
+particular	O
+isolate	O
+to	O
+be	O
+looked	O
+up	O
+using	O
+any	O
+of	O
+its	O
+alternative	O
+identifiers	O
+.	O
+
+A	O
+sequence	O
+search	O
+is	O
+also	O
+possible	O
+using	O
+BLASTN	O
+(	O
+35	O
+)	O
+,	O
+in	O
+order	O
+to	O
+select	O
+isolates	O
+that	O
+have	O
+allele	O
+sequences	O
+identical	O
+to	O
+user	O
+-	O
+entered	O
+query	O
+sequences	O
+.	O
+
+Throughout	O
+SuperCAT	O
+,	O
+clicking	O
+on	O
+a	O
+strain	O
+name	O
+will	O
+pop	O
+up	O
+an	O
+isolate	O
+-	O
+specific	O
+window	O
+showing	O
+all	O
+relevant	O
+information	O
+and	O
+giving	O
+access	O
+to	O
+the	O
+nucleotide	O
+sequences	O
+of	O
+individual	O
+loci	O
+for	O
+that	O
+isolate	O
+.	O
+
+Detailed	O
+information	O
+about	O
+the	O
+MLST	O
+schemes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+loci	O
+names	O
+and	O
+lengths	O
+,	O
+genomic	O
+coordinates	O
+,	O
+literature	O
+references	O
+)	O
+and	O
+their	O
+overlap	O
+,	O
+the	O
+distribution	O
+of	O
+available	O
+loci	O
+among	O
+the	O
+isolates	O
+,	O
+and	O
+the	O
+supertree	O
+reconstruction	O
+procedure	O
+can	O
+be	O
+obtained	O
+by	O
+clicking	O
+the	O
+relevant	O
+links	O
+in	O
+the	O
+header	O
+line	O
+present	O
+at	O
+the	O
+top	O
+of	O
+every	O
+page	O
+.	O
+
+Apart	O
+from	O
+the	O
+basic	O
+functions	O
+for	O
+selecting	O
+and	O
+accessing	O
+strain	O
+information	O
+and	O
+sequence	O
+data	O
+for	O
+all	O
+five	O
+B	B
+.	I
+cereus	I
+group	I
+MLST	O
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+,	O
+the	O
+main	O
+features	O
+of	O
+SuperCAT	O
+relate	O
+to	O
+the	O
+manipulation	O
+of	O
+the	O
+supertrees	O
+constructed	O
+by	O
+the	O
+MRP	O
+approach	O
+.	O
+
+The	O
+global	O
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+based	O
+on	O
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+combination	O
+of	O
+all	O
+five	O
+B	B
+.	I
+cereus	I
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+scheme	O
+-	O
+specific	O
+supertrees	O
+can	O
+be	O
+browsed	O
+according	O
+to	O
+various	O
+user	O
+-	O
+chosen	O
+criteria	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+Isolates	O
+in	O
+the	O
+supertrees	O
+can	O
+be	O
+colored	O
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+species	O
+or	O
+source	O
+of	O
+isolation	O
+.	O
+
+It	O
+is	O
+also	O
+possible	O
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+specifically	O
+mark	O
+in	O
+red	O
+the	O
+current	O
+subset	O
+of	O
+strains	O
+that	O
+has	O
+been	O
+selected	O
+by	O
+the	O
+user	O
+and	O
+to	O
+extract	O
+from	O
+the	O
+supertrees	O
+the	O
+subtree	O
+containing	O
+only	O
+those	O
+isolates	O
+.	O
+
+In	O
+the	O
+case	O
+of	O
+the	O
+multi	O
+-	O
+scheme	O
+supertree	O
+highlighting	O
+of	O
+the	O
+strains	O
+can	O
+be	O
+based	O
+on	O
+genetic	O
+distance	O
+.	O
+
+With	O
+this	O
+option	O
+the	O
+user	O
+can	O
+mark	O
+on	O
+and	O
+/	O
+or	O
+extract	O
+from	O
+the	O
+tree	O
+the	O
+isolates	O
+that	O
+are	O
+genetically	O
+closely	O
+related	O
+to	O
+strains	O
+of	O
+her	O
+/	O
+his	O
+choice	O
+.	O
+
+The	O
+user	O
+can	O
+either	O
+select	O
+strains	O
+that	O
+share	O
+one	O
+or	O
+several	O
+identical	O
+allele	O
+sequences	O
+with	O
+her	O
+/	O
+his	O
+query	O
+isolate	O
+(	O
+s	O
+)	O
+or	O
+that	O
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+at	O
+a	O
+specified	O
+genetic	O
+distance	O
+.	O
+
+Distances	O
+between	O
+isolates	O
+are	O
+computed	O
+by	O
+summing	O
+up	O
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+lengths	O
+of	O
+the	O
+branches	O
+(	O
+in	O
+average	O
+number	O
+of	O
+nucleotide	O
+substitutions	O
+per	O
+site	O
+)	O
+connecting	O
+the	O
+isolates	O
+in	O
+the	O
+supertree	O
+(	O
+known	O
+as	O
+patristic	O
+distances	O
+;	O
+(	O
+36	O
+)	O
+)	O
+.	O
+
+The	O
+genetic	O
+relatedness	O
+search	O
+functions	O
+are	O
+also	O
+available	O
+in	O
+a	O
+separate	O
+page	O
+for	O
+the	O
+user	O
+to	O
+find	O
+closely	O
+related	O
+isolates	O
+without	O
+tree	O
+manipulation	O
+.	O
+
+SuperCAT	O
+allows	O
+to	O
+compare	O
+the	O
+scheme	O
+-	O
+specific	O
+MLST	O
+supertrees	O
+with	O
+each	O
+other	O
+and	O
+with	O
+the	O
+global	O
+supertree	O
+by	O
+using	O
+the	O
+subset	O
+of	O
+isolates	O
+that	O
+are	O
+common	O
+to	O
+all	O
+selected	O
+schemes	O
+.	O
+
+Common	O
+isolates	O
+can	O
+either	O
+be	O
+highlighted	O
+in	O
+red	O
+or	O
+be	O
+extracted	O
+as	O
+subtrees	O
+from	O
+each	O
+supertree	O
+,	O
+which	O
+can	O
+be	O
+used	O
+for	O
+comparing	O
+the	O
+positions	O
+of	O
+the	O
+common	O
+strains	O
+in	O
+the	O
+various	O
+MLST	O
+trees	O
+.	O
+
+For	O
+all	O
+supertree	O
+-	O
+related	O
+options	O
+,	O
+detailed	O
+tree	O
+navigation	O
+can	O
+be	O
+achieved	O
+using	O
+the	O
+various	O
+functions	O
+in	O
+the	O
+ATV	O
+tree	O
+window	O
+when	O
+the	O
+trees	O
+are	O
+displayed	O
+(	O
+17	O
+)	O
+.	O
+
+Figure	O
+2	O
+.	O
+Examples	O
+of	O
+supertree	O
+browsing	O
+and	O
+manipulation	O
+in	O
+SuperCAT	O
+.	O
+
+A	O
+,	O
+supertree	O
+colored	O
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+species	O
+;	O
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+,	O
+specific	O
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+user	O
+-	O
+selected	O
+strains	O
+(	O
+in	O
+red	O
+)	O
+;	O
+C	O
+,	O
+extracted	O
+subtree	O
+containing	O
+only	O
+the	O
+strains	O
+highlighted	O
+in	O
+B	O
+.	O
+
+Trees	O
+are	O
+displayed	O
+using	O
+ATV	O
+(	O
+17	O
+)	O
+.	O
+
+Besides	O
+the	O
+manipulation	O
+of	O
+the	O
+precomputed	O
+supertrees	O
+,	O
+SuperCAT	O
+offers	O
+the	O
+user	O
+the	O
+possibility	O
+to	O
+compute	O
+new	O
+supertrees	O
+by	O
+MRP	O
+using	O
+any	O
+combination	O
+of	O
+strains	O
+,	O
+schemes	O
+and	O
+genes	O
+.	O
+
+Supertree	O
+computations	O
+may	O
+be	O
+extremely	O
+time	O
+consuming	O
+,	O
+ranging	O
+from	O
+a	O
+few	O
+minutes	O
+to	O
+2	O
+-	O
+3	O
+days	O
+with	O
+the	O
+complete	O
+database	O
+.	O
+
+Users	O
+are	O
+therefore	O
+requested	O
+to	O
+enter	O
+their	O
+e	O
+-	O
+mail	O
+addresses	O
+and	O
+will	O
+receive	O
+a	O
+notification	O
+containing	O
+a	O
+link	O
+to	O
+the	O
+results	O
+page	O
+when	O
+the	O
+supertree	O
+is	O
+ready	O
+.	O
+
+Note	O
+that	O
+when	O
+building	O
+a	O
+supertree	O
+for	O
+a	O
+user	O
+-	O
+selected	O
+subset	O
+of	O
+strains	O
+,	O
+the	O
+computation	O
+will	O
+first	O
+include	O
+all	O
+database	O
+isolates	O
+.	O
+
+A	O
+subtree	O
+containing	O
+only	O
+the	O
+user	O
+-	O
+selected	O
+isolates	O
+will	O
+then	O
+be	O
+extracted	O
+from	O
+the	O
+supertree	O
+of	O
+all	O
+strains	O
+.	O
+
+Although	O
+more	O
+time	O
+consuming	O
+,	O
+this	O
+strategy	O
+allows	O
+:	O
+(	O
+i	O
+)	O
+to	O
+avoid	O
+sampling	O
+artefacts	O
+as	O
+phylogenies	O
+built	O
+with	O
+different	O
+isolate	O
+sets	O
+may	O
+vary	O
+and	O
+(	O
+ii	O
+)	O
+to	O
+obtain	O
+relationships	O
+even	O
+if	O
+the	O
+selected	O
+isolates	O
+have	O
+been	O
+typed	O
+using	O
+non	O
+-	O
+overlapping	O
+gene	O
+sets	O
+,	O
+as	O
+the	O
+supertree	O
+of	O
+all	O
+isolates	O
+can	O
+always	O
+be	O
+built	O
+owing	O
+to	O
+the	O
+completely	O
+sequenced	O
+strains	O
+that	O
+are	O
+common	O
+to	O
+all	O
+schemes	O
+.	O
+
+Another	O
+main	O
+feature	O
+of	O
+the	O
+SuperCAT	O
+database	O
+is	O
+that	O
+the	O
+user	O
+can	O
+enter	O
+her	O
+/	O
+his	O
+own	O
+private	O
+sequences	O
+and	O
+conduct	O
+several	O
+sequence	O
+analyses	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+These	O
+analyses	O
+include	O
+:	O
+(	O
+a	O
+)	O
+building	O
+new	O
+supertrees	O
+containing	O
+user	O
+isolates	O
+and	O
+sequences	O
+;	O
+(	O
+b	O
+)	O
+finding	O
+database	O
+isolates	O
+having	O
+sequences	O
+most	O
+similar	O
+to	O
+the	O
+user	O
+'	O
+s	O
+query	O
+sequences	O
+using	O
+an	O
+on	O
+-	O
+line	O
+BLASTN	O
+(	O
+35	O
+)	O
+service	O
+;	O
+and	O
+(	O
+c	O
+)	O
+aligning	O
+user	O
+sequences	O
+to	O
+database	O
+genes	O
+using	O
+the	O
+multiple	O
+sequence	O
+alignment	O
+program	O
+CLUSTALW	O
+(	O
+37	O
+)	O
+.	O
+
+For	O
+the	O
+last	O
+option	O
+,	O
+the	O
+Jalview	O
+editor	O
+(	O
+18	O
+)	O
+is	O
+provided	O
+for	O
+advanced	O
+multiple	O
+alignment	O
+display	O
+.	O
+
+All	O
+user	O
+-	O
+entered	O
+data	O
+must	O
+be	O
+in	O
+FASTA	O
+format	O
+and	O
+can	O
+be	O
+either	O
+copied	O
+and	O
+pasted	O
+into	O
+the	O
+query	O
+forms	O
+or	O
+uploaded	O
+from	O
+text	O
+files	O
+stored	O
+locally	O
+on	O
+the	O
+user	O
+'	O
+s	O
+computer	O
+.	O
+
+Figure	O
+3	O
+.	O
+Examples	O
+of	O
+query	O
+results	O
+in	O
+SuperCAT	O
+.	O
+
+A	O
+,	O
+multi	O
+-	O
+scheme	O
+BLAST	O
+search	O
+with	O
+sequence	O
+alignment	O
+;	O
+B	O
+,	O
+multi	O
+-	O
+scheme	O
+genetic	O
+search	O
+showing	O
+the	O
+list	O
+of	O
+isolates	O
+sharing	O
+one	O
+or	O
+more	O
+sequences	O
+with	O
+a	O
+query	O
+strain	O
+;	O
+C	O
+,	O
+multiple	O
+sequence	O
+alignment	O
+using	O
+Jalview	O
+(	O
+18	O
+)	O
+.	O
+
+All	O
+strain	O
+information	O
+data	O
+,	O
+sequences	O
+and	O
+phylogenetic	O
+trees	O
+,	O
+including	O
+user	O
+-	O
+made	O
+supertrees	O
+and	O
+extracted	O
+subtrees	O
+,	O
+can	O
+be	O
+saved	O
+and	O
+downloaded	O
+freely	O
+from	O
+the	O
+database	O
+.	O
+
+Users	O
+wishing	O
+to	O
+have	O
+their	O
+MLST	O
+data	O
+included	O
+as	O
+part	O
+of	O
+the	O
+SuperCAT	O
+release	O
+(	O
+and	O
+/	O
+or	O
+the	O
+Tourasse	O
+-	O
+Helgason	O
+scheme	O
+-	O
+specific	O
+database	O
+)	O
+are	O
+welcome	O
+to	O
+contact	O
+N	O
+.	O
+J	O
+.	O
+T	O
+.	O
+or	O
+A	O
+.	O
+-	O
+B	O
+.	O
+K	O
+.	O
+at	O
+the	O
+e	O
+-	O
+mail	O
+addresses	O
+given	O
+on	O
+the	O
+Oslo	O
+MLST	O
+server	O
+front	O
+page	O
+.	O
+
+DISCUSSION	O
+AND	O
+FUTURE	O
+DEVELOPMENTS	O
+
+SuperCAT	O
+is	O
+a	O
+newly	O
+created	O
+database	O
+devoted	O
+to	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+of	O
+bacteria	O
+whose	O
+main	O
+objectives	O
+are	O
+to	O
+provide	O
+a	O
+common	O
+MLST	O
+repository	O
+and	O
+means	O
+for	O
+building	O
+a	O
+comprehensive	O
+genetic	O
+analysis	O
+of	O
+the	O
+group	O
+that	O
+has	O
+been	O
+typed	O
+by	O
+five	O
+separate	O
+schemes	O
+.	O
+
+The	O
+database	O
+is	O
+publicly	O
+and	O
+freely	O
+available	O
+at	O
+http	O
+:	O
+/	O
+/	O
+mlstoslo	O
+.	O
+uio	O
+.	O
+no	O
+/	O
+,	O
+along	O
+with	O
+the	O
+database	O
+specific	O
+for	O
+the	O
+combined	O
+scheme	O
+of	O
+(	O
+5	O
+)	O
+.	O
+
+We	O
+plan	O
+to	O
+update	O
+SuperCAT	O
+quarterly	O
+.	O
+
+Future	O
+developments	O
+of	O
+the	O
+database	O
+may	O
+deal	O
+with	O
+refining	O
+the	O
+supertree	O
+-	O
+building	O
+procedure	O
+.	O
+
+In	O
+particular	O
+,	O
+a	O
+new	O
+improved	O
+method	O
+has	O
+recently	O
+been	O
+developed	O
+for	O
+taking	O
+into	O
+account	O
+both	O
+nucleotide	O
+substitutions	O
+and	O
+recombination	O
+events	O
+in	O
+phylogenies	O
+,	O
+as	O
+part	O
+of	O
+the	O
+ClonalFrame	O
+software	O
+,	O
+which	O
+has	O
+been	O
+applied	O
+to	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+and	O
+the	O
+Priest	O
+scheme	O
+(	O
+38	O
+)	O
+.	O
+
+It	O
+would	O
+therefore	O
+be	O
+of	O
+interest	O
+to	O
+examine	O
+the	O
+suitability	O
+of	O
+ClonalFrame	O
+in	O
+the	O
+supertree	O
+context	O
+.	O
+
+It	O
+is	O
+also	O
+tempting	O
+to	O
+extend	O
+the	O
+supertree	O
+analysis	O
+beyond	O
+MLST	O
+data	O
+,	O
+by	O
+incorporating	O
+the	O
+phylogenies	O
+obtained	O
+previously	O
+from	O
+large	O
+-	O
+scale	O
+multilocus	O
+enzyme	O
+electrophoresis	O
+(	O
+MLEE	O
+;	O
+(	O
+3	O
+,	O
+39	O
+-	O
+41	O
+)	O
+)	O
+and	O
+amplified	O
+fragment	O
+length	O
+polymorphism	O
+(	O
+AFLP	O
+;	O
+(	O
+42	O
+-	O
+45	O
+)	O
+)	O
+studies	O
+.	O
+
+The	O
+MRP	O
+framework	O
+is	O
+ideal	O
+since	O
+it	O
+allows	O
+to	O
+integrate	O
+trees	O
+that	O
+can	O
+be	O
+built	O
+from	O
+different	O
+methods	O
+and	O
+data	O
+.	O
+
+As	O
+MLEE	O
+,	O
+AFLP	O
+and	O
+MLST	O
+have	O
+different	O
+levels	O
+of	O
+resolution	O
+,	O
+one	O
+can	O
+hope	O
+that	O
+combining	O
+them	O
+might	O
+provide	O
+an	O
+even	O
+more	O
+robust	O
+supertree	O
+for	O
+the	O
+B	B
+.	I
+cereus	I
+group	I
+.	O
+
+Discovery	O
+of	O
+genes	O
+implicated	O
+in	O
+whirling	O
+disease	O
+infection	O
+and	O
+resistance	O
+in	O
+rainbow	B
+trout	I
+using	O
+genome	O
+-	O
+wide	O
+expression	O
+profiling	O
+
+Abstract	O
+
+Background	O
+
+Whirling	O
+disease	O
+,	O
+caused	O
+by	O
+the	O
+pathogen	O
+Myxobolus	B
+cerebralis	I
+,	O
+afflicts	O
+several	O
+salmonid	O
+species	O
+.	O
+
+Rainbow	B
+trout	I
+are	O
+particularly	O
+susceptible	O
+and	O
+may	O
+suffer	O
+high	O
+mortality	O
+rates	O
+.	O
+
+The	O
+disease	O
+is	O
+persistent	O
+and	O
+spreading	O
+in	O
+hatcheries	O
+and	O
+natural	O
+waters	O
+of	O
+several	O
+countries	O
+,	O
+including	O
+the	O
+U	O
+.	O
+S	O
+.	O
+A	O
+.	O
+,	O
+and	O
+the	O
+economic	O
+losses	O
+attributed	O
+to	O
+whirling	O
+disease	O
+are	O
+substantial	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+genome	O
+-	O
+wide	O
+expression	O
+profiling	O
+using	O
+cDNA	O
+microarrays	O
+was	O
+conducted	O
+for	O
+resistant	O
+Hofer	O
+and	O
+susceptible	O
+Trout	O
+Lodge	O
+rainbow	B
+trout	I
+strains	O
+following	O
+pathogen	O
+exposure	O
+with	O
+the	O
+primary	O
+objective	O
+of	O
+identifying	O
+specific	O
+genes	O
+implicated	O
+in	O
+whirling	O
+disease	O
+resistance	O
+.	O
+
+Results	O
+
+Several	O
+genes	O
+were	O
+significantly	O
+up	O
+-	O
+regulated	O
+in	O
+skin	O
+following	O
+pathogen	O
+exposure	O
+for	O
+both	O
+the	O
+resistant	O
+and	O
+susceptible	O
+rainbow	B
+trout	I
+strains	O
+.	O
+
+For	O
+both	O
+strains	O
+,	O
+response	O
+to	O
+infection	O
+appears	O
+to	O
+be	O
+linked	O
+with	O
+the	O
+interferon	O
+system	O
+.	O
+
+Expression	O
+profiles	O
+for	O
+three	O
+genes	O
+identified	O
+with	O
+microarrays	O
+were	O
+confirmed	O
+with	O
+qRT	O
+-	O
+PCR	O
+.	O
+
+Ubiquitin	O
+-	O
+like	O
+protein	O
+1	O
+was	O
+up	O
+-	O
+regulated	O
+over	O
+100	O
+fold	O
+and	O
+interferon	O
+regulating	O
+factor	O
+1	O
+was	O
+up	O
+-	O
+regulated	O
+over	O
+15	O
+fold	O
+following	O
+pathogen	O
+exposure	O
+for	O
+both	O
+strains	O
+.	O
+
+Expression	O
+of	O
+metallothionein	O
+B	O
+,	O
+which	O
+has	O
+known	O
+roles	O
+in	O
+inflammation	O
+and	O
+immune	O
+response	O
+,	O
+was	O
+up	O
+-	O
+regulated	O
+over	O
+5	O
+fold	O
+in	O
+the	O
+resistant	O
+Hofer	O
+strain	O
+but	O
+was	O
+unchanged	O
+in	O
+the	O
+susceptible	O
+Trout	O
+Lodge	O
+strain	O
+following	O
+pathogen	O
+exposure	O
+.	O
+
+Conclusion	O
+
+The	O
+present	O
+study	O
+has	O
+provided	O
+an	O
+initial	O
+view	O
+into	O
+the	O
+genetic	O
+basis	O
+underlying	O
+immune	O
+response	O
+and	O
+resistance	O
+of	O
+rainbow	B
+trout	I
+to	O
+the	O
+whirling	O
+disease	O
+parasite	O
+.	O
+
+The	O
+identified	O
+genes	O
+have	O
+allowed	O
+us	O
+to	O
+gain	O
+insight	O
+into	O
+the	O
+molecular	O
+mechanisms	O
+implicated	O
+in	O
+salmonid	O
+immune	O
+response	O
+and	O
+resistance	O
+to	O
+whirling	O
+disease	O
+infection	O
+.	O
+
+Background	O
+
+Whirling	O
+disease	O
+was	O
+first	O
+described	O
+among	O
+farmed	O
+rainbow	B
+trout	I
+(	O
+Oncorhynchus	B
+mykiss	I
+)	O
+,	O
+a	O
+native	O
+North	O
+American	O
+salmonid	O
+species	O
+,	O
+introduced	O
+to	O
+Germany	O
+as	O
+a	O
+food	O
+fish	O
+in	O
+the	O
+late	O
+1800s	O
+[	O
+1	O
+]	O
+.	O
+
+Whirling	O
+disease	O
+is	O
+associated	O
+with	O
+systemic	O
+infections	O
+by	O
+the	O
+myxozoan	O
+Myxobolus	B
+cerebralis	I
+,	O
+a	O
+parasite	O
+with	O
+presumed	O
+origins	O
+among	O
+salmonid	O
+fish	O
+in	O
+Eurasia	O
+[	O
+2	O
+,	O
+3	O
+]	O
+.	O
+
+Rainbow	B
+trout	I
+are	O
+highly	O
+susceptible	O
+to	O
+whirling	O
+disease	O
+and	O
+the	O
+introduction	O
+of	O
+the	O
+parasite	O
+to	O
+the	O
+U	O
+.	O
+S	O
+.	O
+A	O
+.	O
+in	O
+the	O
+1950s	O
+had	O
+immediate	O
+economic	O
+impacts	O
+on	O
+salmonid	O
+hatcheries	O
+in	O
+both	O
+eastern	O
+and	O
+western	O
+states	O
+[	O
+2	O
+]	O
+.	O
+
+The	O
+parasite	O
+has	O
+a	O
+broad	O
+worldwide	O
+distribution	O
+and	O
+has	O
+been	O
+identified	O
+in	O
+25	O
+states	O
+in	O
+the	O
+U	O
+.	O
+S	O
+.	O
+A	O
+.	O
+where	O
+salmonid	O
+fish	O
+are	O
+present	O
+[	O
+4	O
+]	O
+.	O
+
+Salmonid	O
+hatcheries	O
+throughout	O
+the	O
+U	O
+.	O
+S	O
+.	O
+A	O
+have	O
+suffered	O
+drastic	O
+economic	O
+losses	O
+due	O
+to	O
+whirling	O
+disease	O
+outbreaks	O
+.	O
+
+The	O
+disease	O
+has	O
+more	O
+recently	O
+been	O
+recognized	O
+as	O
+the	O
+principal	O
+cause	O
+of	O
+major	O
+population	O
+declines	O
+among	O
+wild	O
+rainbow	B
+trout	I
+populations	O
+in	O
+the	O
+intermountain	O
+region	O
+of	O
+the	O
+U	O
+.	O
+S	O
+.	O
+A	O
+with	O
+serious	O
+negative	O
+impacts	O
+on	O
+sportfishing	O
+and	O
+allied	O
+industries	O
+[	O
+5	O
+-	O
+7	O
+]	O
+.	O
+
+Additionally	O
+,	O
+concerns	O
+continue	O
+over	O
+the	O
+potential	O
+negative	O
+ecologic	O
+impacts	O
+of	O
+whirling	O
+disease	O
+on	O
+wild	O
+salmonid	O
+populations	O
+,	O
+particularly	O
+threatened	O
+or	O
+endangered	O
+salmonids	O
+such	O
+as	O
+bull	B
+trout	I
+(	O
+Salvelinus	B
+confluentus	I
+)	O
+,	O
+cutthroat	B
+trout	I
+(	O
+Oncorhynchus	B
+clarki	I
+)	O
+,	O
+and	O
+steelhead	B
+(	O
+Oncorhynchus	B
+mykiss	I
+)	O
+[	O
+8	O
+,	O
+9	O
+]	O
+.	O
+
+Myxobolus	B
+cerebralis	I
+has	O
+a	O
+complex	O
+life	O
+cycle	O
+that	O
+includes	O
+two	O
+alternate	O
+hosts	O
+,	O
+a	O
+salmonid	O
+fish	O
+and	O
+an	O
+oligochaete	O
+worm	O
+,	O
+Tubifex	B
+tubifex	I
+[	O
+10	O
+,	O
+11	O
+]	O
+.	O
+
+Infection	O
+in	O
+the	O
+salmonid	O
+host	O
+begins	O
+when	O
+microscopic	O
+waterborne	O
+actinospore	O
+stages	O
+of	O
+M	B
+.	I
+cerebralis	I
+are	O
+released	O
+from	O
+the	O
+worm	O
+and	O
+contact	O
+the	O
+skin	O
+of	O
+the	O
+fish	O
+host	O
+.	O
+
+Actinospores	O
+,	O
+also	O
+referred	O
+to	O
+as	O
+triactinomyxons	O
+for	O
+M	B
+.	I
+cerebralis	I
+,	O
+attach	O
+preferentially	O
+to	O
+fins	O
+and	O
+the	O
+buccal	O
+cavity	O
+where	O
+they	O
+release	O
+one	O
+or	O
+more	O
+of	O
+three	O
+coiled	O
+polar	O
+filaments	O
+which	O
+penetrate	O
+and	O
+then	O
+anchor	O
+them	O
+to	O
+the	O
+epidermis	O
+[	O
+12	O
+]	O
+.	O
+
+Within	O
+minutes	O
+the	O
+sporoplasm	O
+,	O
+which	O
+contains	O
+64	O
+internal	O
+cells	O
+,	O
+migrates	O
+from	O
+the	O
+triactinomxyon	O
+to	O
+deeper	O
+layers	O
+of	O
+the	O
+epidermis	O
+,	O
+an	O
+action	O
+that	O
+may	O
+be	O
+facilitated	O
+by	O
+parasite	O
+proteases	O
+[	O
+13	O
+-	O
+15	O
+]	O
+.	O
+
+Aggregates	O
+and	O
+single	O
+cells	O
+from	O
+the	O
+sporoplasm	O
+then	O
+begin	O
+mitotic	O
+replication	O
+within	O
+two	O
+h	O
+of	O
+initial	O
+infection	O
+,	O
+alternating	O
+between	O
+inter	O
+and	O
+intracellular	O
+locations	O
+,	O
+a	O
+process	O
+that	O
+may	O
+also	O
+depend	O
+upon	O
+parasite	O
+coded	O
+protease	O
+activity	O
+[	O
+15	O
+,	O
+16	O
+]	O
+.	O
+
+Over	O
+the	O
+next	O
+10	O
+h	O
+at	O
+water	O
+temperatures	O
+of	O
+15	O
+degrees	O
+C	O
+,	O
+parasites	O
+within	O
+host	O
+epithelial	O
+cells	O
+further	O
+divide	O
+by	O
+the	O
+process	O
+of	O
+endogeny	O
+or	O
+cell	O
+within	O
+cell	O
+replication	O
+prior	O
+to	O
+release	O
+and	O
+then	O
+penetration	O
+of	O
+new	O
+host	O
+cells	O
+.	O
+
+Between	O
+12	O
+and	O
+20	O
+h	O
+post	O
+infection	O
+,	O
+the	O
+number	O
+of	O
+parasite	O
+cells	O
+present	O
+in	O
+the	O
+epidermis	O
+steadily	O
+declines	O
+until	O
+new	O
+stages	O
+are	O
+observed	O
+in	O
+the	O
+subcutis	O
+at	O
+48	O
+h	O
+.	O
+
+Degenerative	O
+stages	O
+observed	O
+in	O
+the	O
+epidermis	O
+between	O
+12	O
+and	O
+20	O
+h	O
+are	O
+suspected	O
+to	O
+be	O
+a	O
+result	O
+of	O
+the	O
+action	O
+of	O
+the	O
+host	O
+immune	O
+response	O
+,	O
+although	O
+the	O
+cellular	O
+and	O
+or	O
+humoral	O
+factors	O
+involved	O
+are	O
+not	O
+currently	O
+known	O
+.	O
+
+After	O
+a	O
+brief	O
+residence	O
+in	O
+the	O
+subcutis	O
+,	O
+parasite	O
+stages	O
+are	O
+presumed	O
+to	O
+migrate	O
+to	O
+proximal	O
+nervous	O
+tissues	O
+,	O
+initially	O
+in	O
+peripheral	O
+and	O
+then	O
+more	O
+central	O
+locations	O
+[	O
+16	O
+]	O
+.	O
+
+Migration	O
+and	O
+potential	O
+replication	O
+of	O
+parasite	O
+stages	O
+in	O
+nervous	O
+tissue	O
+ensues	O
+over	O
+the	O
+next	O
+16	O
+d	O
+with	O
+the	O
+first	O
+parasites	O
+exiting	O
+to	O
+invade	O
+cartilage	O
+observed	O
+at	O
+20	O
+d	O
+post	O
+infection	O
+[	O
+16	O
+]	O
+.	O
+
+Feeding	O
+on	O
+cartilage	O
+may	O
+induce	O
+a	O
+host	O
+inflammatory	O
+response	O
+that	O
+constricts	O
+the	O
+spinal	O
+cord	O
+,	O
+brain	O
+stem	O
+,	O
+and	O
+caudal	O
+nerves	O
+resulting	O
+in	O
+the	O
+erratic	O
+swimming	O
+behavior	O
+(	O
+whirling	O
+)	O
+and	O
+black	O
+tail	O
+observed	O
+among	O
+fish	O
+with	O
+acute	O
+whirling	O
+disease	O
+[	O
+17	O
+]	O
+.	O
+
+An	O
+additional	O
+impact	O
+of	O
+cartilage	O
+destruction	O
+are	O
+permanent	O
+deformities	O
+to	O
+the	O
+skeletal	O
+system	O
+that	O
+may	O
+increase	O
+vulnerability	O
+to	O
+predation	O
+and	O
+impair	O
+ability	O
+to	O
+forage	O
+for	O
+food	O
+[	O
+1	O
+]	O
+.	O
+
+The	O
+final	O
+developmental	O
+stages	O
+of	O
+the	O
+parasite	O
+in	O
+the	O
+fish	O
+are	O
+environmentally	O
+resistant	O
+spore	O
+stages	O
+(	O
+myxospores	O
+)	O
+which	O
+remained	O
+trapped	O
+in	O
+cartilage	O
+or	O
+bone	O
+[	O
+18	O
+]	O
+.	O
+
+Death	O
+of	O
+infected	O
+fish	O
+or	O
+ingestion	O
+by	O
+fish	O
+or	O
+avian	O
+predators	O
+releases	O
+myxospores	O
+from	O
+the	O
+fish	O
+tissues	O
+and	O
+they	O
+may	O
+be	O
+ingested	O
+by	O
+the	O
+second	O
+host	O
+,	O
+the	O
+benthic	O
+dwelling	O
+oligochaete	O
+T	B
+.	I
+tubifex	I
+[	O
+19	O
+]	O
+.	O
+
+A	O
+second	O
+developmental	O
+cycle	O
+then	O
+occurs	O
+under	O
+the	O
+mucosal	O
+lining	O
+of	O
+the	O
+intestine	O
+that	O
+results	O
+in	O
+the	O
+release	O
+of	O
+thousands	O
+of	O
+the	O
+actinospore	O
+(	O
+triactinomyxon	O
+)	O
+stages	O
+potentially	O
+over	O
+the	O
+entire	O
+lifetime	O
+of	O
+the	O
+individual	O
+oligochaete	O
+[	O
+20	O
+]	O
+.	O
+
+Susceptibility	O
+to	O
+whirling	O
+disease	O
+in	O
+U	O
+.	O
+S	O
+.	O
+rainbow	B
+trout	I
+strains	O
+is	O
+pervasive	O
+with	O
+only	O
+two	O
+of	O
+the	O
+tested	O
+native	O
+strains	O
+displaying	O
+any	O
+degree	O
+of	O
+resistance	O
+,	O
+which	O
+may	O
+be	O
+inconsistent	O
+and	O
+relatively	O
+moderate	O
+[	O
+21	O
+,	O
+22	O
+]	O
+.	O
+
+Hatchery	O
+rainbow	B
+trout	I
+in	O
+Germany	O
+(	O
+Hofer	O
+strain	O
+)	O
+,	O
+however	O
+,	O
+have	O
+acquired	O
+a	O
+degree	O
+of	O
+resistance	O
+to	O
+whirling	O
+disease	O
+that	O
+is	O
+consistently	O
+much	O
+higher	O
+than	O
+any	O
+domestic	O
+rainbow	O
+strains	O
+and	O
+comparable	O
+to	O
+that	O
+of	O
+brown	B
+trout	I
+(	O
+Salmon	B
+trutta	I
+)	O
+,	O
+which	O
+are	O
+native	O
+to	O
+Europe	O
+and	O
+typically	O
+asymptomatic	O
+following	O
+infection	O
+[	O
+23	O
+]	O
+.	O
+
+Laboratory	O
+tests	O
+comparing	O
+rainbow	B
+trout	I
+strains	O
+under	O
+the	O
+same	O
+environmental	O
+conditions	O
+and	O
+pathogen	O
+exposure	O
+indicate	O
+that	O
+the	O
+Hofer	O
+strain	O
+'	O
+s	O
+ability	O
+to	O
+combat	O
+M	B
+.	I
+cerebralis	I
+infection	O
+has	O
+a	O
+genetic	O
+basis	O
+.	O
+
+Recently	O
+,	O
+controlled	O
+crosses	O
+of	O
+the	O
+Hofer	O
+strain	O
+and	O
+a	O
+susceptible	O
+strain	O
+(	O
+Colorado	O
+River	O
+rainbow	B
+trout	I
+[	O
+CRR	O
+]	O
+)	O
+demonstrated	O
+that	O
+resistance	O
+to	O
+whirling	O
+disease	O
+was	O
+inherited	O
+by	O
+progeny	O
+[	O
+24	O
+]	O
+and	O
+heritability	O
+estimates	O
+are	O
+currently	O
+underway	O
+.	O
+
+The	O
+discovery	O
+of	O
+the	O
+resistant	O
+Hofer	O
+strain	O
+allowed	O
+us	O
+to	O
+conduct	O
+an	O
+intraspecific	O
+comparison	O
+of	O
+susceptible	O
+and	O
+resistant	O
+rainbow	B
+trout	I
+in	O
+order	O
+to	O
+gain	O
+insight	O
+into	O
+the	O
+genetic	O
+basis	O
+underlying	O
+whirling	O
+disease	O
+susceptibility	O
+for	O
+this	O
+species	O
+.	O
+
+Gene	O
+expression	O
+profiling	O
+,	O
+through	O
+the	O
+use	O
+of	O
+microarrays	O
+,	O
+is	O
+an	O
+extremely	O
+high	O
+-	O
+throughput	O
+method	O
+to	O
+discover	O
+specific	O
+genes	O
+and	O
+pathways	O
+involved	O
+in	O
+a	O
+disease	O
+phenotype	O
+without	O
+the	O
+bias	O
+of	O
+a	O
+candidate	O
+gene	O
+approach	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+microarray	O
+analysis	O
+was	O
+used	O
+to	O
+examine	O
+expression	O
+changes	O
+in	O
+a	O
+resistant	O
+and	O
+susceptible	O
+strain	O
+of	O
+rainbow	B
+trout	I
+following	O
+exposure	O
+to	O
+M	B
+.	I
+cerebralis	I
+,	O
+the	O
+pathogen	O
+causing	O
+whirling	O
+disease	O
+.	O
+
+We	O
+have	O
+found	O
+several	O
+genes	O
+significantly	O
+up	O
+-	O
+regulated	O
+in	O
+both	O
+the	O
+resistant	O
+and	O
+susceptible	O
+strain	O
+that	O
+appear	O
+to	O
+be	O
+involved	O
+in	O
+host	O
+response	O
+to	O
+infection	O
+.	O
+
+We	O
+have	O
+also	O
+found	O
+a	O
+gene	O
+which	O
+is	O
+significantly	O
+up	O
+-	O
+regulated	O
+in	O
+the	O
+resistant	O
+but	O
+remains	O
+unchanged	O
+in	O
+the	O
+susceptible	O
+rainbow	B
+trout	I
+strain	O
+following	O
+pathogen	O
+exposure	O
+that	O
+is	O
+a	O
+likely	O
+candidate	O
+gene	O
+for	O
+involvement	O
+in	O
+conferring	O
+whirling	O
+disease	O
+resistance	O
+.	O
+
+Results	O
+and	O
+Discussion	O
+
+Quantitative	O
+PCR	O
+conducted	O
+on	O
+caudal	O
+fin	O
+tissues	O
+at	O
+two	O
+hours	O
+post	O
+exposure	O
+to	O
+M	B
+.	I
+cerebralis	I
+demonstrated	O
+each	O
+fish	O
+strain	O
+had	O
+similar	O
+initial	O
+pathogen	O
+loads	O
+,	O
+although	O
+there	O
+was	O
+substantial	O
+variation	O
+between	O
+individual	O
+fish	O
+within	O
+each	O
+strain	O
+.	O
+
+The	O
+mean	O
+parasite	O
+copy	O
+numbers	O
+per	O
+host	O
+cell	O
+were	O
+1	O
+.	O
+20	O
+x	O
+106	O
+(	O
+SD	O
+1	O
+.	O
+53	O
+x	O
+106	O
+)	O
+for	O
+the	O
+Hofer	O
+and	O
+1	O
+.	O
+04	O
+x	O
+106	O
+(	O
+SD	O
+0	O
+.	O
+91	O
+x	O
+106	O
+)	O
+for	O
+the	O
+Trout	O
+Lodge	O
+.	O
+
+These	O
+mean	O
+values	O
+and	O
+standard	O
+deviations	O
+are	O
+similar	O
+to	O
+those	O
+obtained	O
+in	O
+additional	O
+studies	O
+of	O
+susceptible	O
+rainbow	B
+trout	I
+when	O
+examined	O
+at	O
+early	O
+time	O
+points	O
+post	O
+TAM	O
+exposure	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+In	O
+order	O
+to	O
+study	O
+genes	O
+involved	O
+in	O
+whirling	O
+disease	O
+response	O
+,	O
+resistant	O
+and	O
+susceptible	O
+rainbow	B
+trout	I
+strains	O
+were	O
+exposed	O
+to	O
+M	B
+.	I
+cerebralis	I
+and	O
+RNA	O
+from	O
+skin	O
+tissue	O
+was	O
+converted	O
+to	O
+cDNA	O
+and	O
+hybridized	O
+onto	O
+microarrays	O
+.	O
+
+Relative	O
+gene	O
+expression	O
+for	O
+exposed	O
+and	O
+unexposed	O
+controls	O
+for	O
+each	O
+strain	O
+was	O
+compared	O
+and	O
+the	O
+list	O
+of	O
+differentially	O
+expressed	O
+genes	O
+for	O
+both	O
+strains	O
+is	O
+found	O
+in	O
+Table	O
+1	O
+.	O
+
+A	O
+combined	O
+total	O
+of	O
+17	O
+genes	O
+or	O
+features	O
+(	O
+14	O
+annotated	O
+genes	O
+,	O
+3	O
+unknown	O
+features	O
+)	O
+were	O
+differentially	O
+expressed	O
+in	O
+one	O
+or	O
+both	O
+strains	O
+following	O
+pathogen	O
+exposure	O
+and	O
+are	O
+involved	O
+with	O
+rainbow	B
+trout	I
+infection	O
+response	O
+to	O
+whirling	O
+disease	O
+exposure	O
+.	O
+
+Several	O
+of	O
+these	O
+genes	O
+were	O
+found	O
+in	O
+different	O
+locations	O
+on	O
+the	O
+array	O
+as	O
+unique	O
+expressed	O
+sequence	O
+tag	O
+(	O
+EST	O
+)	O
+clones	O
+and	O
+their	O
+repeated	O
+presence	O
+on	O
+the	O
+significance	O
+gene	O
+lists	O
+provides	O
+additional	O
+support	O
+for	O
+their	O
+involvement	O
+in	O
+the	O
+whirling	O
+disease	O
+phenotype	O
+.	O
+
+The	O
+small	O
+number	O
+of	O
+genes	O
+found	O
+potentially	O
+indicates	O
+that	O
+only	O
+a	O
+few	O
+genes	O
+contribute	O
+to	O
+the	O
+phenotypic	O
+differences	O
+found	O
+between	O
+resistant	O
+Hofer	O
+and	O
+susceptible	O
+Trout	O
+Lodge	O
+,	O
+at	O
+least	O
+in	O
+terms	O
+of	O
+differential	O
+gene	O
+expression	O
+,	O
+during	O
+early	O
+disease	O
+progression	O
+in	O
+the	O
+skin	O
+.	O
+
+In	O
+the	O
+microarray	O
+statistical	O
+analysis	O
+,	O
+when	O
+the	O
+delta	O
+value	O
+was	O
+adjusted	O
+even	O
+slightly	O
+lower	O
+,	O
+the	O
+FDR	O
+estimate	O
+increases	O
+from	O
+0	O
+%	O
+to	O
+~	O
+78	O
+%	O
+.	O
+
+Since	O
+increasing	O
+the	O
+FDR	O
+cut	O
+-	O
+off	O
+to	O
+such	O
+a	O
+high	O
+percentage	O
+would	O
+dramatically	O
+reduce	O
+power	O
+,	O
+we	O
+chose	O
+to	O
+leave	O
+the	O
+gene	O
+list	O
+small	O
+with	O
+an	O
+estimated	O
+FDR	O
+of	O
+0	O
+%	O
+.	O
+
+This	O
+type	O
+of	O
+dramatic	O
+increase	O
+in	O
+FDR	O
+estimation	O
+is	O
+additional	O
+support	O
+that	O
+there	O
+are	O
+not	O
+many	O
+genes	O
+differentially	O
+expressed	O
+in	O
+response	O
+to	O
+whirling	O
+disease	O
+infection	O
+for	O
+our	O
+chosen	O
+tissue	O
+and	O
+time	O
+points	O
+.	O
+
+Different	O
+salmonid	O
+microarray	O
+platforms	O
+,	O
+such	O
+as	O
+those	O
+available	O
+from	O
+Oregon	O
+State	O
+University	O
+and	O
+Michigan	O
+State	O
+University	O
+,	O
+or	O
+different	O
+tissues	O
+and	O
+time	O
+points	O
+may	O
+produce	O
+additional	O
+candidate	O
+genes	O
+.	O
+
+A	O
+recent	O
+time	O
+course	O
+study	O
+used	O
+a	O
+candidate	O
+gene	O
+approach	O
+to	O
+identify	O
+four	O
+genes	O
+(	O
+TGF	O
+-	O
+beta	O
+,	O
+IL	O
+-	O
+1	O
+beta	O
+1	O
+,	O
+IL	O
+-	O
+1	O
+beta	O
+2	O
+,	O
+and	O
+COX	O
+-	O
+2	O
+)	O
+that	O
+were	O
+significantly	O
+up	O
+-	O
+regulated	O
+by	O
+both	O
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+in	O
+response	O
+to	O
+whirling	O
+disease	O
+infection	O
+[	O
+25	O
+]	O
+.	O
+
+These	O
+genes	O
+and	O
+their	O
+downstream	O
+effectors	O
+were	O
+not	O
+identified	O
+in	O
+the	O
+current	O
+microarray	O
+study	O
+,	O
+likely	O
+due	O
+to	O
+many	O
+differences	O
+in	O
+experimental	O
+design	O
+between	O
+the	O
+two	O
+studies	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+pathogen	O
+exposure	O
+levels	O
+,	O
+tissue	O
+types	O
+,	O
+water	O
+temperatures	O
+,	O
+age	O
+of	O
+fish	O
+at	O
+exposure	O
+,	O
+etc	O
+.	O
+)	O
+.	O
+
+While	O
+downstream	O
+effectors	O
+of	O
+these	O
+genes	O
+were	O
+present	O
+on	O
+the	O
+microarray	O
+,	O
+only	O
+one	O
+of	O
+the	O
+four	O
+genes	O
+(	O
+COX	O
+-	O
+2	O
+)	O
+was	O
+actually	O
+present	O
+on	O
+the	O
+microarray	O
+.	O
+
+It	O
+is	O
+our	O
+hope	O
+that	O
+future	O
+genome	O
+sequencing	O
+will	O
+enable	O
+the	O
+construction	O
+of	O
+more	O
+comprehensive	O
+microarray	O
+platforms	O
+for	O
+economically	O
+important	O
+aquaculture	O
+species	O
+,	O
+such	O
+as	O
+Atlantic	B
+salmon	I
+and	O
+rainbow	B
+trout	I
+.	O
+
+All	O
+significant	O
+genes	O
+identified	O
+by	O
+the	O
+current	O
+microarray	O
+study	O
+were	O
+up	O
+-	O
+regulated	O
+following	O
+pathogen	O
+exposure	O
+for	O
+one	O
+or	O
+both	O
+strains	O
+.	O
+
+Therefore	O
+,	O
+it	O
+appears	O
+that	O
+both	O
+strains	O
+are	O
+undergoing	O
+transcriptional	O
+activation	O
+to	O
+defend	O
+against	O
+whirling	O
+disease	O
+infection	O
+and	O
+thus	O
+,	O
+are	O
+exclusively	O
+employing	O
+positive	O
+regulation	O
+for	O
+the	O
+genes	O
+examined	O
+in	O
+skin	O
+during	O
+early	O
+disease	O
+progression	O
+.	O
+
+The	O
+normal	O
+caveats	O
+that	O
+apply	O
+for	O
+microarray	O
+studies	O
+(	O
+gene	O
+discovery	O
+is	O
+limited	O
+by	O
+transcripts	O
+on	O
+arrays	O
+,	O
+differences	O
+at	O
+transcriptional	O
+level	O
+may	O
+not	O
+cause	O
+phenotypic	O
+differences	O
+,	O
+results	O
+are	O
+dependent	O
+upon	O
+tissue	O
+type	O
+and	O
+time	O
+point	O
+chosen	O
+,	O
+etc	O
+.	O
+)	O
+apply	O
+for	O
+this	O
+study	O
+.	O
+
+Additionally	O
+,	O
+the	O
+comparison	O
+of	O
+two	O
+rainbow	B
+trout	I
+strains	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+resistant	O
+versus	O
+susceptible	O
+)	O
+added	O
+another	O
+layer	O
+of	O
+complexity	O
+to	O
+the	O
+analysis	O
+.	O
+
+We	O
+chose	O
+to	O
+not	O
+directly	O
+compare	O
+the	O
+two	O
+strains	O
+because	O
+there	O
+could	O
+be	O
+expression	O
+differences	O
+between	O
+them	O
+,	O
+due	O
+to	O
+divergence	O
+following	O
+strain	O
+isolation	O
+,	O
+that	O
+are	O
+unrelated	O
+to	O
+the	O
+whirling	O
+disease	O
+phenotype	O
+.	O
+
+With	O
+that	O
+in	O
+mind	O
+,	O
+the	O
+two	O
+strains	O
+were	O
+first	O
+compared	O
+entirely	O
+separately	O
+from	O
+each	O
+other	O
+to	O
+discover	O
+expression	O
+differences	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+for	O
+each	O
+strain	O
+.	O
+
+Only	O
+the	O
+genes	O
+responding	O
+to	O
+infection	O
+,	O
+and	O
+therefore	O
+implicated	O
+in	O
+the	O
+whirling	O
+disease	O
+phenotype	O
+,	O
+were	O
+compared	O
+between	O
+the	O
+two	O
+strains	O
+for	O
+differential	O
+gene	O
+expression	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+A	O
+limitation	O
+of	O
+this	O
+approach	O
+to	O
+our	O
+study	O
+is	O
+that	O
+constitutively	O
+expressed	O
+transcripts	O
+which	O
+are	O
+differentially	O
+expressed	O
+between	O
+the	O
+two	O
+strains	O
+that	O
+contribute	O
+to	O
+the	O
+whirling	O
+disease	O
+phenotype	O
+cannot	O
+be	O
+identified	O
+.	O
+
+Microarray	O
+analysis	O
+of	O
+genes	O
+differentially	O
+expressed	O
+in	O
+the	O
+resistant	O
+Hofer	O
+strain	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+
+A	O
+total	O
+of	O
+16	O
+genes	O
+or	O
+features	O
+(	O
+13	O
+annotated	O
+genes	O
+,	O
+3	O
+unknown	O
+features	O
+)	O
+were	O
+up	O
+-	O
+regulated	O
+in	O
+the	O
+resistant	O
+Hofer	O
+strain	O
+following	O
+pathogen	O
+exposure	O
+.	O
+
+All	O
+13	O
+annotated	O
+genes	O
+have	O
+been	O
+previously	O
+implicated	O
+in	O
+host	O
+immune	O
+response	O
+for	O
+other	O
+infectious	O
+diseases	O
+.	O
+
+Viral	B
+Hemorrhagic	I
+Septicemia	I
+Virus	I
+(	O
+VHSV	B
+)	O
+induced	O
+protein	O
+and	O
+neighbor	O
+of	O
+COX	O
+-	O
+4	O
+are	O
+the	O
+only	O
+annotated	O
+genes	O
+without	O
+known	O
+molecular	O
+functions	O
+.	O
+
+A	O
+common	O
+link	O
+between	O
+the	O
+majority	O
+of	O
+annotated	O
+genes	O
+with	O
+known	O
+molecular	O
+functions	O
+is	O
+an	O
+involvement	O
+in	O
+the	O
+interferon	O
+system	O
+.	O
+
+The	O
+interferon	O
+system	O
+is	O
+one	O
+of	O
+the	O
+first	O
+lines	O
+of	O
+host	O
+defense	O
+against	O
+invading	O
+pathogens	O
+for	O
+vertebrates	O
+(	O
+for	O
+review	O
+see	O
+[	O
+26	O
+]	O
+)	O
+,	O
+including	O
+teleost	B
+fish	I
+(	O
+for	O
+review	O
+see	O
+[	O
+27	O
+]	O
+)	O
+.	O
+
+Other	O
+economically	O
+important	O
+salmonid	O
+pathogens	O
+,	O
+such	O
+as	O
+infectious	B
+pancreatic	I
+necrosis	I
+virus	I
+and	O
+infectious	B
+salmon	I
+anaemia	I
+virus	I
+have	O
+been	O
+found	O
+to	O
+activate	O
+both	O
+type	O
+I	O
+and	O
+type	O
+II	O
+interferon	O
+(	O
+IFN	O
+)	O
+responses	O
+in	O
+the	O
+Atlantic	B
+salmon	I
+host	O
+following	O
+infection	O
+[	O
+28	O
+]	O
+.	O
+
+Interferons	O
+are	O
+cytokine	O
+proteins	O
+that	O
+are	O
+secreted	O
+following	O
+infection	O
+and	O
+play	O
+a	O
+critical	O
+role	O
+in	O
+both	O
+innate	O
+and	O
+adaptive	O
+immunity	O
+.	O
+
+The	O
+IFN	O
+system	O
+has	O
+been	O
+most	O
+widely	O
+researched	O
+in	O
+mammals	O
+and	O
+studies	O
+have	O
+found	O
+that	O
+type	O
+I	O
+IFN	O
+(	O
+mammalian	O
+IFN	O
+-	O
+alpha	O
+/	O
+beta	O
+)	O
+are	O
+secreted	O
+by	O
+the	O
+pathogen	O
+-	O
+infected	O
+cells	O
+as	O
+part	O
+of	O
+a	O
+rapid	O
+initial	O
+immune	O
+response	O
+while	O
+Type	O
+II	O
+IFN	O
+(	O
+mammalian	O
+IFN	O
+-	O
+gamma	O
+)	O
+is	O
+secreted	O
+by	O
+natural	O
+killer	O
+(	O
+NK	O
+)	O
+and	O
+T	O
+cells	O
+and	O
+plays	O
+a	O
+more	O
+central	O
+role	O
+in	O
+the	O
+second	O
+wave	O
+of	O
+immune	O
+response	O
+.	O
+
+To	O
+cope	O
+with	O
+the	O
+myriad	O
+of	O
+host	O
+infections	O
+,	O
+the	O
+interferon	O
+system	O
+is	O
+highly	O
+complex	O
+and	O
+involves	O
+the	O
+regulation	O
+of	O
+hundreds	O
+of	O
+genes	O
+[	O
+29	O
+,	O
+30	O
+]	O
+.	O
+
+Specifically	O
+,	O
+type	O
+I	O
+IFN	O
+acts	O
+to	O
+increase	O
+MHC	O
+class	O
+I	O
+expression	O
+for	O
+antigen	O
+presentation	O
+[	O
+31	O
+]	O
+,	O
+promote	O
+T	O
+cell	O
+survival	O
+[	O
+32	O
+]	O
+,	O
+inhibit	O
+cell	O
+proliferation	O
+[	O
+33	O
+]	O
+,	O
+mediate	O
+apoptosis	O
+[	O
+26	O
+]	O
+,	O
+and	O
+increase	O
+NK	O
+cell	O
+activity	O
+[	O
+34	O
+]	O
+.	O
+
+Type	O
+II	O
+IFN	O
+acts	O
+to	O
+increase	O
+both	O
+MHC	O
+class	O
+I	O
+and	O
+II	O
+expression	O
+for	O
+antigen	O
+presentation	O
+[	O
+29	O
+]	O
+,	O
+stimulate	O
+macrophages	O
+to	O
+kill	O
+engulfed	O
+pathogens	O
+[	O
+35	O
+]	O
+,	O
+induce	O
+apoptosis	O
+[	O
+36	O
+]	O
+,	O
+and	O
+regulate	O
+leukocyte	O
+-	O
+endothelium	O
+interactions	O
+[	O
+37	O
+]	O
+in	O
+addition	O
+to	O
+many	O
+other	O
+immune	O
+-	O
+related	O
+activities	O
+.	O
+
+It	O
+is	O
+informative	O
+to	O
+examine	O
+the	O
+functional	O
+roles	O
+of	O
+each	O
+gene	O
+'	O
+s	O
+encoded	O
+protein	O
+specifically	O
+to	O
+better	O
+understand	O
+the	O
+part	O
+each	O
+plays	O
+,	O
+both	O
+individually	O
+and	O
+as	O
+interconnected	O
+components	O
+,	O
+in	O
+host	O
+immune	O
+response	O
+.	O
+
+Expression	O
+of	O
+the	O
+interferon	O
+-	O
+induced	O
+35	O
+kDa	O
+protein	O
+is	O
+induced	O
+by	O
+IFN	O
+and	O
+it	O
+is	O
+involved	O
+in	O
+cytokine	O
+signalling	O
+[	O
+38	O
+]	O
+.	O
+
+Interferon	O
+regulatory	O
+factor	O
+1	O
+(	O
+IRF	O
+-	O
+1	O
+)	O
+and	O
+interferon	O
+regulatory	O
+factor	O
+7	O
+(	O
+IRF	O
+-	O
+7	O
+)	O
+are	O
+transcription	O
+factors	O
+that	O
+induce	O
+expression	O
+of	O
+IFN	O
+responsive	O
+genes	O
+[	O
+39	O
+,	O
+40	O
+]	O
+.	O
+
+Additionally	O
+,	O
+IRF	O
+-	O
+1	O
+is	O
+involved	O
+in	O
+apoptosis	O
+and	O
+cell	O
+cycle	O
+regulation	O
+related	O
+to	O
+tumor	O
+suppression	O
+[	O
+41	O
+]	O
+.	O
+
+Similarly	O
+,	O
+cyclin	O
+-	O
+dependent	O
+kinase	O
+4	O
+inhibitor	O
+B	O
+(	O
+p15	O
+-	O
+INK4b	O
+)	O
+plays	O
+a	O
+role	O
+in	O
+apoptosis	O
+[	O
+42	O
+]	O
+,	O
+cell	O
+cycle	O
+regulation	O
+[	O
+42	O
+]	O
+,	O
+and	O
+tumor	O
+suppression	O
+[	O
+43	O
+]	O
+and	O
+can	O
+be	O
+induced	O
+by	O
+the	O
+cytokine	O
+TGF	O
+-	O
+beta	O
+[	O
+44	O
+]	O
+.	O
+
+Gig2	O
+is	O
+an	O
+interferon	O
+-	O
+inducible	O
+protein	O
+that	O
+is	O
+likely	O
+part	O
+of	O
+the	O
+JAK	O
+-	O
+STAT	O
+signal	O
+transduction	O
+pathway	O
+[	O
+45	O
+]	O
+.	O
+
+Ubiquitin	O
+and	O
+the	O
+proteasome	O
+subunit	O
+beta	O
+type	O
+8	O
+precursor	O
+are	O
+both	O
+members	O
+of	O
+the	O
+ubiquitin	O
+-	O
+proteasome	O
+system	O
+(	O
+for	O
+review	O
+see	O
+[	O
+26	O
+]	O
+)	O
+,	O
+which	O
+serves	O
+to	O
+degrade	O
+proteins	O
+via	O
+proteolysis	O
+.	O
+
+These	O
+degraded	O
+proteins	O
+can	O
+originate	O
+from	O
+an	O
+invading	O
+pathogen	O
+and	O
+are	O
+displayed	O
+on	O
+MHC	O
+class	O
+I	O
+proteins	O
+.	O
+
+The	O
+beta	O
+-	O
+2	O
+-	O
+microglobulin	O
+is	O
+an	O
+integral	O
+component	O
+of	O
+MHC	O
+class	O
+I	O
+proteins	O
+and	O
+is	O
+therefore	O
+involved	O
+in	O
+antigen	O
+processing	O
+and	O
+presentation	O
+to	O
+cytotoxic	O
+T	O
+cells	O
+[	O
+46	O
+]	O
+.	O
+
+Haptoglobin	O
+binds	O
+hemoglobin	O
+and	O
+limits	O
+its	O
+availability	O
+to	O
+infectious	O
+bacteria	O
+,	O
+thus	O
+preventing	O
+bacterial	O
+proliferation	O
+in	O
+a	O
+wound	O
+[	O
+47	O
+]	O
+.	O
+
+The	O
+PPAR	O
+-	O
+alpha	O
+-	O
+interacting	O
+complex	O
+protein	O
+285	O
+is	O
+a	O
+transcriptional	O
+co	O
+-	O
+activator	O
+with	O
+helicase	O
+activity	O
+[	O
+48	O
+]	O
+and	O
+has	O
+sequence	O
+similarity	O
+to	O
+a	O
+rainbow	B
+trout	I
+VHSV	B
+-	O
+induced	O
+protein	O
+.	O
+
+Gene	O
+expression	O
+of	O
+metallothionein	O
+B	O
+(	O
+MT	O
+-	O
+B	O
+)	O
+is	O
+induced	O
+by	O
+several	O
+metal	O
+ions	O
+[	O
+49	O
+]	O
+,	O
+cytokines	O
+[	O
+50	O
+-	O
+52	O
+]	O
+,	O
+and	O
+stress	O
+hormones	O
+[	O
+53	O
+-	O
+55	O
+]	O
+.	O
+
+MT	O
+proteins	O
+are	O
+believed	O
+to	O
+play	O
+diverse	O
+functional	O
+roles	O
+in	O
+inflammation	O
+,	O
+immune	O
+response	O
+,	O
+apoptosis	O
+,	O
+tumor	O
+suppression	O
+,	O
+and	O
+detoxification	O
+(	O
+for	O
+reviews	O
+see	O
+[	O
+55	O
+,	O
+56	O
+]	O
+)	O
+.	O
+
+Microarray	O
+analysis	O
+of	O
+genes	O
+differentially	O
+expressed	O
+in	O
+the	O
+susceptible	O
+Trout	O
+Lodge	O
+strain	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+
+A	O
+total	O
+of	O
+six	O
+genes	O
+or	O
+features	O
+(	O
+five	O
+annotated	O
+genes	O
+,	O
+one	O
+unknown	O
+feature	O
+)	O
+were	O
+up	O
+-	O
+regulated	O
+in	O
+the	O
+susceptible	O
+Trout	O
+Lodge	O
+strain	O
+following	O
+pathogen	O
+exposure	O
+.	O
+
+Only	O
+one	O
+of	O
+the	O
+significant	O
+genes	O
+for	O
+Trout	O
+Lodge	O
+,	O
+which	O
+has	O
+sequence	O
+similarity	O
+to	O
+CC	O
+chemokine	O
+SCYA113	O
+,	O
+was	O
+not	O
+also	O
+differentially	O
+expressed	O
+in	O
+Hofer	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+.	O
+
+The	O
+CC	O
+chemokine	O
+SCYA113	O
+gene	O
+is	O
+a	O
+member	O
+of	O
+the	O
+CC	O
+chemokine	O
+family	O
+,	O
+which	O
+guides	O
+leukocytes	O
+to	O
+sites	O
+of	O
+infection	O
+and	O
+inflammation	O
+(	O
+for	O
+review	O
+see	O
+[	O
+57	O
+]	O
+)	O
+.	O
+
+The	O
+fewer	O
+number	O
+of	O
+significant	O
+genes	O
+found	O
+for	O
+Trout	O
+Lodge	O
+relative	O
+to	O
+Hofer	O
+may	O
+indicate	O
+a	O
+decrease	O
+in	O
+transcriptional	O
+activation	O
+for	O
+this	O
+susceptible	O
+strain	O
+.	O
+
+There	O
+is	O
+,	O
+however	O
+,	O
+likely	O
+some	O
+degree	O
+of	O
+overlap	O
+in	O
+both	O
+strains	O
+'	O
+response	O
+to	O
+pathogen	O
+exposure	O
+due	O
+to	O
+the	O
+fact	O
+that	O
+several	O
+genes	O
+were	O
+up	O
+-	O
+regulated	O
+in	O
+both	O
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+ubiquitin	O
+-	O
+like	O
+protein	O
+1	O
+,	O
+IRF	O
+-	O
+1	O
+,	O
+and	O
+PPAR	O
+-	O
+alpha	O
+-	O
+interacting	O
+protein	O
+Gig2	O
+)	O
+.	O
+
+A	O
+critical	O
+phase	O
+in	O
+the	O
+early	O
+stages	O
+of	O
+M	B
+.	I
+cerebralis	I
+infection	O
+in	O
+trout	O
+is	O
+invasion	O
+and	O
+intracellular	O
+replication	O
+,	O
+processes	O
+that	O
+begin	O
+as	O
+early	O
+as	O
+one	O
+hour	O
+post	O
+exposure	O
+to	O
+triactinomyxons	O
+[	O
+16	O
+]	O
+.	O
+
+A	O
+role	O
+for	O
+accumulated	O
+ubiquinated	O
+proteins	O
+in	O
+the	O
+lysosome	O
+in	O
+the	O
+killing	O
+of	O
+Mycobacterium	B
+tuberculosis	I
+has	O
+recently	O
+been	O
+described	O
+that	O
+has	O
+implications	O
+for	O
+a	O
+range	O
+of	O
+intracellular	O
+infections	O
+[	O
+58	O
+]	O
+and	O
+some	O
+similar	O
+responses	O
+to	O
+infection	O
+may	O
+be	O
+occurring	O
+for	O
+both	O
+resistant	O
+and	O
+susceptible	O
+strains	O
+.	O
+
+Microarray	O
+analysis	O
+of	O
+genes	O
+differentially	O
+expressed	O
+between	O
+resistant	O
+and	O
+susceptible	O
+strains	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+
+Of	O
+the	O
+genes	O
+differentially	O
+expressed	O
+in	O
+response	O
+to	O
+pathogen	O
+exposure	O
+for	O
+both	O
+strains	O
+,	O
+only	O
+metallothionein	O
+B	O
+shows	O
+a	O
+statistically	O
+significant	O
+difference	O
+in	O
+expression	O
+between	O
+the	O
+two	O
+strains	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+MT	O
+-	O
+B	O
+was	O
+found	O
+to	O
+be	O
+up	O
+-	O
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+in	O
+the	O
+resistant	O
+Hofer	O
+strain	O
+following	O
+pathogen	O
+exposure	O
+but	O
+remained	O
+unchanged	O
+in	O
+the	O
+susceptible	O
+Trout	O
+Lodge	O
+strain	O
+.	O
+
+As	O
+previously	O
+noted	O
+,	O
+metallothionein	O
+has	O
+been	O
+implicated	O
+in	O
+a	O
+broad	O
+range	O
+of	O
+functional	O
+capacities	O
+,	O
+including	O
+inflammatory	O
+and	O
+immune	O
+responses	O
+.	O
+
+Several	O
+cytokines	O
+can	O
+induce	O
+metallothionein	O
+expression	O
+including	O
+IFN	O
+[	O
+59	O
+-	O
+61	O
+]	O
+,	O
+interleukin	O
+-	O
+1	O
+[	O
+50	O
+]	O
+,	O
+interleukin	O
+-	O
+6	O
+[	O
+51	O
+]	O
+,	O
+and	O
+tumor	O
+necrosis	O
+factor	O
+-	O
+alpha	O
+[	O
+52	O
+]	O
+.	O
+
+Metallothionein	O
+has	O
+been	O
+shown	O
+to	O
+mediate	O
+leukocyte	O
+chemotaxis	O
+and	O
+has	O
+been	O
+hypothesized	O
+to	O
+serve	O
+as	O
+an	O
+early	O
+"	O
+danger	O
+signal	O
+"	O
+during	O
+times	O
+of	O
+stress	O
+or	O
+infection	O
+to	O
+activate	O
+an	O
+immune	O
+response	O
+[	O
+62	O
+]	O
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+
+The	O
+functional	O
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+metallothionein	O
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+CC	O
+chemokine	O
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+at	O
+least	O
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+terms	O
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+leukocyte	O
+chemotaxis	O
+,	O
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+certainly	O
+of	O
+interest	O
+since	O
+these	O
+genes	O
+displayed	O
+quite	O
+distinct	O
+expression	O
+profiles	O
+.	O
+
+Metallothionein	O
+was	O
+up	O
+-	O
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+the	O
+resistant	O
+Hofer	O
+strain	O
+and	O
+CC	O
+chemokine	O
+SCYA113	O
+was	O
+up	O
+-	O
+regulated	O
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+the	O
+susceptible	O
+Trout	O
+Lodge	O
+strain	O
+(	O
+although	O
+CC	O
+chemokine	O
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+did	O
+not	O
+pass	O
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+significance	O
+cut	O
+-	O
+off	O
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+be	O
+considered	O
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+
+This	O
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+two	O
+genes	O
+,	O
+capable	O
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+similar	O
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+,	O
+may	O
+indicate	O
+that	O
+leukocyte	O
+movements	O
+to	O
+,	O
+and	O
+their	O
+activities	O
+once	O
+at	O
+,	O
+the	O
+infection	O
+site	O
+are	O
+key	O
+factors	O
+in	O
+determining	O
+resistance	O
+versus	O
+susceptibility	O
+to	O
+whirling	O
+disease	O
+.	O
+
+Evaluations	O
+by	O
+light	O
+microscopy	O
+and	O
+qPCR	O
+for	O
+M	B
+.	I
+cerebralis	I
+genomic	O
+DNA	O
+of	O
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+rainbow	B
+trout	I
+exposed	O
+to	O
+triactinomyxons	O
+demonstrates	O
+Hofer	O
+more	O
+efficiently	O
+eliminates	O
+invading	O
+parasites	O
+in	O
+the	O
+skin	O
+(	O
+M	O
+.	O
+Adkison	O
+,	O
+pers	O
+.	O
+comm	O
+.	O
+)	O
+.	O
+
+While	O
+the	O
+parasite	O
+effectively	O
+penetrates	O
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+epidermis	O
+in	O
+both	O
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+,	O
+significantly	O
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+the	O
+migration	O
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+the	O
+skin	O
+to	O
+the	O
+nerves	O
+as	O
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+at	O
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+d	O
+post	O
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+.	O
+
+A	O
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+host	O
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+invading	O
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+,	O
+even	O
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+susceptible	O
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+,	O
+is	O
+suggested	O
+by	O
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+prior	O
+light	O
+and	O
+electron	O
+microscopy	O
+studies	O
+that	O
+demonstrate	O
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+increase	O
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+in	O
+the	O
+skin	O
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+as	O
+early	O
+as	O
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+h	O
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+then	O
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+24	O
+h	O
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+-	O
+exposure	O
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+[	O
+12	O
+,	O
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+,	O
+63	O
+]	O
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+
+The	O
+difference	O
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+
+For	O
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+'	O
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+a	O
+zinc	O
+-	O
+finger	O
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+[	O
+64	O
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+expression	O
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+.	O
+
+All	O
+biological	O
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+of	O
+this	O
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+protein	O
+should	O
+be	O
+considered	O
+when	O
+examining	O
+the	O
+complexities	O
+of	O
+host	O
+immune	O
+response	O
+.	O
+
+Additionally	O
+,	O
+upstream	O
+regulators	O
+of	O
+metallothionein	O
+expression	O
+could	O
+be	O
+the	O
+true	O
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+cause	O
+of	O
+the	O
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+since	O
+a	O
+gene	O
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+determine	O
+if	O
+a	O
+gene	O
+is	O
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+contributing	O
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+a	O
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+(	O
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+.	O
+e	O
+.	O
+,	O
+cause	O
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+)	O
+.	O
+
+Validation	O
+of	O
+microarray	O
+results	O
+by	O
+qRT	O
+-	O
+PCR	O
+
+Quantitative	O
+RT	O
+-	O
+PCR	O
+(	O
+qRT	O
+-	O
+PCR	O
+)	O
+confirmed	O
+the	O
+microarrays	O
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+the	O
+genes	O
+up	O
+-	O
+regulated	O
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+Trout	O
+Lodge	O
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+,	O
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+-	O
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+(	O
+Figure	O
+2	O
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+
+The	O
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+-	O
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+results	O
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+each	O
+gene	O
+,	O
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+response	O
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+
+MT	O
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+the	O
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+.	O
+
+This	O
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+The	O
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+-	O
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+-	O
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+-	O
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+.	O
+
+Many	O
+other	O
+studies	O
+have	O
+also	O
+observed	O
+this	O
+pattern	O
+of	O
+greater	O
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+-	O
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+(	O
+for	O
+examples	O
+see	O
+[	O
+65	O
+,	O
+66	O
+]	O
+,	O
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+is	O
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+-	O
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+-	O
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+
+Given	O
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+,	O
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+believe	O
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+into	O
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+.	O
+
+Potential	O
+future	O
+studies	O
+
+While	O
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+interferon	O
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+to	O
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+further	O
+study	O
+,	O
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+have	O
+distinct	O
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+functions	O
+in	O
+other	O
+systems	O
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+
+Furthermore	O
+,	O
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+the	O
+interplay	O
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+pathways	O
+/	O
+networks	O
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+classified	O
+as	O
+discrete	O
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+have	O
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+phenotypic	O
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+quantitative	O
+traits	O
+[	O
+67	O
+]	O
+.	O
+
+Multiple	O
+avenues	O
+of	O
+research	O
+should	O
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+future	O
+studies	O
+,	O
+using	O
+the	O
+candidate	O
+genes	O
+presented	O
+here	O
+as	O
+an	O
+initial	O
+guide	O
+,	O
+due	O
+to	O
+the	O
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+relationships	O
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+hosts	O
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+pathogens	O
+.	O
+
+For	O
+instance	O
+,	O
+the	O
+migration	O
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+and	O
+their	O
+subsequent	O
+activity	O
+in	O
+the	O
+skin	O
+are	O
+likely	O
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+critical	O
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+.	O
+
+Additionally	O
+,	O
+it	O
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+feasible	O
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+.	O
+
+For	O
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+,	O
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+-	O
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+rainbow	B
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+.	O
+
+All	O
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+should	O
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+.	O
+
+Finally	O
+,	O
+upstream	O
+regulators	O
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+metallothionein	O
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+could	O
+be	O
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+the	O
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+gene	O
+expression	O
+study	O
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+determine	O
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+is	O
+directly	O
+contributing	O
+to	O
+a	O
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+(	O
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+.	O
+e	O
+.	O
+,	O
+cause	O
+versus	O
+downstream	O
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+)	O
+.	O
+
+The	O
+expression	O
+profiles	O
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+a	O
+variety	O
+of	O
+metallothionein	O
+upstream	O
+regulators	O
+,	O
+such	O
+as	O
+cytokines	O
+and	O
+metal	O
+transcription	O
+factor	O
+(	O
+MTF	O
+-	O
+1	O
+)	O
+,	O
+could	O
+be	O
+evaluated	O
+in	O
+a	O
+time	O
+course	O
+study	O
+during	O
+early	O
+disease	O
+progression	O
+to	O
+identify	O
+additional	O
+candidate	O
+genes	O
+.	O
+
+A	O
+QTL	O
+mapping	O
+approach	O
+could	O
+also	O
+be	O
+used	O
+to	O
+identify	O
+particular	O
+chromosomal	O
+regions	O
+directly	O
+contributing	O
+to	O
+the	O
+disease	O
+phenotype	O
+.	O
+
+Conclusion	O
+
+The	O
+present	O
+study	O
+has	O
+provided	O
+the	O
+first	O
+examination	O
+into	O
+the	O
+genetic	O
+basis	O
+underlying	O
+rainbow	B
+trout	I
+'	O
+s	O
+immune	O
+response	O
+and	O
+resistance	O
+to	O
+the	O
+whirling	O
+disease	O
+pathogen	O
+.	O
+
+Several	O
+genes	O
+were	O
+significantly	O
+up	O
+-	O
+regulated	O
+in	O
+skin	O
+following	O
+pathogen	O
+exposure	O
+for	O
+both	O
+the	O
+resistant	O
+Hofer	O
+and	O
+susceptible	O
+Trout	O
+Lodge	O
+rainbow	B
+trout	I
+strains	O
+.	O
+
+For	O
+both	O
+strains	O
+,	O
+response	O
+to	O
+infection	O
+appears	O
+to	O
+be	O
+linked	O
+with	O
+the	O
+interferon	O
+system	O
+.	O
+
+Metallothionein	O
+B	O
+is	O
+differentially	O
+expressed	O
+between	O
+the	O
+resistant	O
+and	O
+susceptible	O
+strains	O
+and	O
+is	O
+a	O
+good	O
+candidate	O
+for	O
+future	O
+whirling	O
+disease	O
+resistance	O
+studies	O
+.	O
+
+The	O
+identified	O
+genes	O
+have	O
+allowed	O
+us	O
+to	O
+gain	O
+initial	O
+insight	O
+into	O
+the	O
+molecular	O
+mechanisms	O
+involved	O
+in	O
+a	O
+salmonid	O
+host	O
+'	O
+s	O
+immune	O
+response	O
+and	O
+resistance	O
+to	O
+whirling	O
+disease	O
+infection	O
+.	O
+
+Methods	O
+
+Animal	O
+care	O
+,	O
+pathogen	O
+exposure	O
+,	O
+and	O
+RNA	O
+preparation	O
+
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+rainbow	B
+trout	I
+strains	O
+were	O
+reared	O
+in	O
+35	O
+gallon	O
+aquaria	O
+with	O
+15	O
+degrees	O
+C	O
+flow	O
+-	O
+through	O
+well	O
+water	O
+for	O
+nine	O
+weeks	O
+post	O
+-	O
+hatch	O
+,	O
+with	O
+each	O
+fish	O
+weighing	O
+approximately	O
+6	O
+.	O
+5	O
+grams	O
+prior	O
+to	O
+pathogen	O
+exposure	O
+.	O
+
+Individuals	O
+from	O
+each	O
+strain	O
+(	O
+n	O
+=	O
+60	O
+)	O
+were	O
+exposed	O
+to	O
+2	O
+,	O
+000	O
+triactinomyxons	O
+(	O
+TAMs	O
+)	O
+per	O
+fish	O
+for	O
+one	O
+hour	O
+.	O
+
+Additional	O
+fish	O
+(	O
+n	O
+=	O
+60	O
+)	O
+from	O
+both	O
+strains	O
+served	O
+as	O
+unexposed	O
+controls	O
+,	O
+which	O
+were	O
+treated	O
+identically	O
+to	O
+exposed	O
+fish	O
+at	O
+all	O
+experimental	O
+stages	O
+other	O
+than	O
+their	O
+lack	O
+of	O
+pathogen	O
+exposure	O
+.	O
+
+Fish	O
+were	O
+then	O
+kept	O
+under	O
+standard	O
+aquaculture	O
+conditions	O
+until	O
+euthanized	O
+.	O
+
+TaqMan	O
+PCR	O
+for	O
+the	O
+quantitative	O
+evaluation	O
+of	O
+genomic	O
+parasite	O
+DNA	O
+was	O
+employed	O
+to	O
+confirm	O
+that	O
+fish	O
+in	O
+both	O
+the	O
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+groups	O
+received	O
+equal	O
+amounts	O
+of	O
+parasite	O
+exposure	O
+.	O
+
+At	O
+two	O
+hours	O
+post	O
+TAM	O
+exposure	O
+,	O
+6	O
+fish	O
+in	O
+each	O
+exposed	O
+group	O
+were	O
+removed	O
+and	O
+euthanized	O
+with	O
+an	O
+overdose	O
+of	O
+benzocaine	O
+at	O
+a	O
+concentration	O
+of	O
+500	O
+mg	O
+/	O
+L	O
+.	O
+
+Caudal	O
+fins	O
+were	O
+removed	O
+posterior	O
+to	O
+the	O
+peduncle	O
+and	O
+used	O
+as	O
+the	O
+tissue	O
+for	O
+a	O
+quantiative	O
+TaqMan	O
+assay	O
+following	O
+procedures	O
+described	O
+by	O
+Kelley	O
+et	O
+al	O
+.	O
+
+[	O
+68	O
+]	O
+.	O
+
+Microarray	O
+studies	O
+examining	O
+skin	O
+four	O
+hours	O
+after	O
+pathogen	O
+exposure	O
+did	O
+not	O
+identify	O
+any	O
+genes	O
+differentially	O
+expressed	O
+between	O
+Trout	O
+Lodge	O
+and	O
+Hofer	O
+strains	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Therefore	O
+,	O
+we	O
+chose	O
+a	O
+later	O
+time	O
+point	O
+(	O
+24	O
+hours	O
+after	O
+exposure	O
+)	O
+so	O
+that	O
+early	O
+host	O
+immune	O
+response	O
+was	O
+more	O
+likely	O
+to	O
+be	O
+fully	O
+underway	O
+and	O
+significant	O
+expression	O
+changes	O
+could	O
+be	O
+detected	O
+.	O
+
+After	O
+the	O
+24	O
+hour	O
+incubation	O
+period	O
+,	O
+all	O
+fish	O
+were	O
+euthanized	O
+with	O
+an	O
+overdose	O
+of	O
+benzocaine	O
+at	O
+a	O
+concentration	O
+of	O
+500	O
+mg	O
+/	O
+L	O
+.	O
+
+Each	O
+fish	O
+was	O
+euthanized	O
+individually	O
+and	O
+the	O
+caudal	O
+fin	O
+(	O
+largely	O
+comprised	O
+of	O
+skin	O
+tissue	O
+)	O
+was	O
+removed	O
+posterior	O
+to	O
+the	O
+peduncle	O
+.	O
+
+The	O
+fin	O
+was	O
+immediately	O
+placed	O
+into	O
+2	O
+x	O
+Nucleic	O
+Acid	O
+Purification	O
+Lysis	O
+Solution	O
+supplied	O
+with	O
+ABI	O
+'	O
+s	O
+TransPrep	O
+Chemistry	O
+kit	O
+(	O
+Applied	O
+Biosystems	O
+,	O
+Foster	O
+City	O
+,	O
+CA	O
+)	O
+to	O
+stop	O
+further	O
+gene	O
+expression	O
+changes	O
+.	O
+
+Total	O
+RNA	O
+was	O
+extracted	O
+from	O
+the	O
+fin	O
+of	O
+each	O
+individual	O
+using	O
+the	O
+ABI	O
+Prism	O
+(	O
+TM	O
+)	O
+TransPrep	O
+system	O
+with	O
+the	O
+ABI	O
+Prism	O
+(	O
+TM	O
+)	O
+6100	O
+Nucleic	O
+Acid	O
+PrepStation	O
+according	O
+to	O
+manufacturer	O
+instructions	O
+.	O
+
+RNA	O
+quality	O
+was	O
+assessed	O
+by	O
+agarose	O
+gel	O
+electrophoresis	O
+and	O
+RNA	O
+concentrations	O
+were	O
+measured	O
+using	O
+a	O
+ND	O
+-	O
+1000	O
+spectrophotometer	O
+(	O
+NanoDrop	O
+Technologies	O
+,	O
+Wilmington	O
+,	O
+DE	O
+)	O
+.	O
+
+Starting	O
+total	O
+RNA	O
+yields	O
+were	O
+not	O
+sufficient	O
+for	O
+microarray	O
+hybridizations	O
+due	O
+to	O
+the	O
+small	O
+amount	O
+of	O
+caudal	O
+fin	O
+tissue	O
+present	O
+on	O
+these	O
+young	O
+fish	O
+.	O
+
+Therefore	O
+,	O
+250	O
+-	O
+1000	O
+ng	O
+of	O
+total	O
+RNA	O
+was	O
+used	O
+as	O
+the	O
+starting	O
+material	O
+to	O
+create	O
+amplified	O
+RNA	O
+(	O
+aRNA	O
+)	O
+indirectly	O
+labeled	O
+with	O
+Cy3	O
+or	O
+Cy5	O
+fluorescent	O
+dyes	O
+(	O
+GE	O
+Healthcare	O
+,	O
+Buckinghamshire	O
+,	O
+UK	O
+)	O
+using	O
+the	O
+Amino	O
+Allyl	O
+MessageAmp	O
+(	O
+TM	O
+)	O
+II	O
+aRNA	O
+Amplification	O
+kit	O
+according	O
+to	O
+manufacturer	O
+instructions	O
+(	O
+Ambion	O
+,	O
+Austin	O
+,	O
+TX	O
+)	O
+.	O
+
+Microarray	O
+hybridization	O
+and	O
+data	O
+analysis	O
+
+Salmonid	O
+cDNA	O
+microarrays	O
+(	O
+GRASP16k	O
+v2	O
+.	O
+0	O
+)	O
+were	O
+obtained	O
+from	O
+consortium	O
+for	O
+Genomic	O
+Research	O
+on	O
+Atlantic	O
+Salmon	O
+(	O
+cGRASP	O
+)	O
+and	O
+details	O
+of	O
+microarray	O
+development	O
+and	O
+fabrication	O
+can	O
+be	O
+found	O
+in	O
+von	O
+Schalburg	O
+et	O
+al	O
+.	O
+
+[	O
+69	O
+]	O
+.	O
+
+These	O
+arrays	O
+contain	O
+13	O
+,	O
+421	O
+Atlantic	B
+salmon	I
+and	O
+2	O
+,	O
+576	O
+rainbow	B
+trout	I
+cDNA	O
+features	O
+and	O
+have	O
+been	O
+successfully	O
+used	O
+for	O
+several	O
+previous	O
+rainbow	B
+trout	I
+gene	O
+expression	O
+studies	O
+[	O
+70	O
+-	O
+73	O
+]	O
+.	O
+
+For	O
+each	O
+rainbow	B
+trout	I
+strain	O
+,	O
+competitive	O
+hybridization	O
+was	O
+conducted	O
+on	O
+every	O
+array	O
+using	O
+equal	O
+amounts	O
+(	O
+8	O
+mu	O
+g	O
+)	O
+of	O
+differentially	O
+labeled	O
+aRNA	O
+from	O
+one	O
+control	O
+fish	O
+and	O
+one	O
+exposed	O
+fish	O
+.	O
+
+Four	O
+biological	O
+replicates	O
+were	O
+performed	O
+for	O
+each	O
+experimental	O
+condition	O
+and	O
+dye	O
+-	O
+sample	O
+coupling	O
+was	O
+swapped	O
+between	O
+biological	O
+replicates	O
+in	O
+a	O
+balanced	O
+block	O
+design	O
+.	O
+
+Prehybridization	O
+washes	O
+for	O
+all	O
+microarrays	O
+included	O
+:	O
+2	O
+x	O
+5	O
+min	O
+in	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+,	O
+5	O
+x	O
+1	O
+min	O
+in	O
+NANOpure	O
+H2O	O
+with	O
+0	O
+.	O
+5	O
+mM	O
+dithiothreotol	O
+,	O
+1	O
+min	O
+in	O
+near	O
+boiling	O
+nanopure	O
+H2O	O
+,	O
+centrifugation	O
+for	O
+2	O
+min	O
+at	O
+1500	O
+RPM	O
+.	O
+
+To	O
+reduce	O
+background	O
+,	O
+the	O
+microarrays	O
+were	O
+next	O
+incubated	O
+for	O
+90	O
+min	O
+in	O
+5	O
+x	O
+SSC	O
+,	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+,	O
+3	O
+%	O
+BSA	O
+(	O
+Fraction	O
+V	O
+)	O
+at	O
+49	O
+degrees	O
+C	O
+,	O
+washed	O
+3	O
+x	O
+20	O
+s	O
+in	O
+nanopure	O
+H2O	O
+,	O
+and	O
+dried	O
+by	O
+centrifugation	O
+for	O
+5	O
+min	O
+at	O
+1500	O
+RPM	O
+.	O
+
+The	O
+labeled	O
+aRNA	O
+samples	O
+were	O
+competitively	O
+hybridized	O
+to	O
+microarrays	O
+prewarmed	O
+to	O
+49	O
+degrees	O
+C	O
+for	O
+16	O
+hours	O
+in	O
+a	O
+formamide	O
+-	O
+based	O
+buffer	O
+(	O
+Genisphere	O
+,	O
+Hatfield	O
+,	O
+PA	O
+)	O
+with	O
+LNA	O
+dT	O
+blocker	O
+(	O
+Genisphere	O
+)	O
+.	O
+
+Posthybridization	O
+washes	O
+for	O
+all	O
+microarrays	O
+included	O
+:	O
+1	O
+x	O
+10	O
+min	O
+in	O
+2	O
+x	O
+SSC	O
+,	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+prewarmed	O
+to	O
+49	O
+degrees	O
+C	O
+,	O
+2	O
+x	O
+5	O
+min	O
+in	O
+2	O
+x	O
+SSC	O
+,	O
+0	O
+.	O
+1	O
+%	O
+SDS	O
+at	O
+room	O
+temperature	O
+,	O
+2	O
+x	O
+5	O
+min	O
+1	O
+x	O
+SSC	O
+at	O
+room	O
+temperature	O
+,	O
+2	O
+x	O
+5	O
+min	O
+0	O
+.	O
+1	O
+x	O
+SSC	O
+at	O
+room	O
+temperature	O
+.	O
+
+Slides	O
+were	O
+then	O
+dried	O
+by	O
+centrifugation	O
+and	O
+immediately	O
+scanned	O
+using	O
+an	O
+Agilent	O
+G2565BA	O
+Microarray	O
+Scanner	O
+(	O
+Agilent	O
+Technologies	O
+,	O
+Santa	O
+Clara	O
+,	O
+CA	O
+)	O
+.	O
+
+Data	O
+underwent	O
+local	O
+background	O
+subtraction	O
+and	O
+LOWESS	O
+normalization	O
+using	O
+Agilent	O
+'	O
+s	O
+Feature	O
+Extraction	O
+software	O
+.	O
+
+Raw	O
+and	O
+processed	O
+gene	O
+expression	O
+data	O
+have	O
+been	O
+deposited	O
+into	O
+the	O
+NCBI	O
+Gene	O
+Expression	O
+Omnibus	O
+[	O
+74	O
+]	O
+(	O
+series	O
+GSE8631	O
+)	O
+and	O
+are	O
+in	O
+compliance	O
+with	O
+MIAME	O
+guidelines	O
+.	O
+
+The	O
+Significance	O
+Analysis	O
+of	O
+Microarrays	O
+(	O
+SAM	O
+)	O
+software	O
+package	O
+[	O
+75	O
+]	O
+was	O
+used	O
+to	O
+identify	O
+differentially	O
+expressed	O
+genes	O
+between	O
+exposed	O
+and	O
+unexposed	O
+control	O
+fish	O
+for	O
+each	O
+rainbow	B
+trout	I
+strain	O
+.	O
+
+Both	O
+a	O
+Wilcoxon	O
+rank	O
+sum	O
+and	O
+a	O
+modified	O
+t	O
+-	O
+test	O
+were	O
+conducted	O
+with	O
+1	O
+,	O
+000	O
+permutations	O
+and	O
+the	O
+minimum	O
+fold	O
+change	O
+cut	O
+-	O
+off	O
+was	O
+set	O
+to	O
+2	O
+.	O
+0	O
+up	O
+-	O
+or	O
+down	O
+-	O
+regulated	O
+.	O
+
+A	O
+false	O
+discovery	O
+rate	O
+(	O
+FDR	O
+)	O
+of	O
+0	O
+.	O
+00	O
+%	O
+was	O
+estimated	O
+for	O
+both	O
+strains	O
+.	O
+
+To	O
+determine	O
+statistically	O
+significant	O
+differences	O
+between	O
+the	O
+Hofer	O
+and	O
+Trout	O
+Lodge	O
+strains	O
+,	O
+a	O
+Welch	O
+'	O
+s	O
+t	O
+-	O
+test	O
+(	O
+P	O
+-	O
+value	O
+<	O
+0	O
+.	O
+01	O
+)	O
+was	O
+implemented	O
+in	O
+Microsoft	O
+Excel	O
+between	O
+the	O
+log	O
+ratios	O
+(	O
+exposed	O
+/	O
+control	O
+)	O
+for	O
+each	O
+strain	O
+for	O
+all	O
+genes	O
+that	O
+were	O
+significant	O
+for	O
+at	O
+least	O
+one	O
+strain	O
+in	O
+the	O
+SAM	O
+program	O
+.	O
+
+Quantitative	O
+RT	O
+-	O
+PCR	O
+
+Microarray	O
+expression	O
+results	O
+were	O
+validated	O
+by	O
+qRT	O
+-	O
+PCR	O
+for	O
+several	O
+identified	O
+genes	O
+.	O
+
+Prior	O
+to	O
+qRT	O
+-	O
+PCR	O
+,	O
+80	O
+ng	O
+of	O
+total	O
+RNA	O
+was	O
+reverse	O
+transcribed	O
+from	O
+each	O
+biological	O
+replicate	O
+used	O
+for	O
+the	O
+microarray	O
+study	O
+along	O
+with	O
+two	O
+additional	O
+samples	O
+(	O
+total	O
+n	O
+=	O
+6	O
+per	O
+experimental	O
+condition	O
+)	O
+using	O
+the	O
+QuantiScript	O
+Reverse	O
+Transcriptase	O
+kit	O
+(	O
+Qiagen	O
+,	O
+Valencia	O
+,	O
+CA	O
+)	O
+according	O
+to	O
+manufacturer	O
+instructions	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+microarray	O
+experiments	O
+,	O
+the	O
+template	O
+RNA	O
+was	O
+not	O
+amplified	O
+before	O
+cDNA	O
+synthesis	O
+.	O
+
+EST	O
+clone	O
+sequences	O
+from	O
+the	O
+cGRASP	O
+microarray	O
+were	O
+used	O
+to	O
+design	O
+primers	O
+for	O
+genes	O
+undergoing	O
+validation	O
+,	O
+along	O
+with	O
+a	O
+beta	O
+-	O
+actin	O
+reference	O
+gene	O
+used	O
+for	O
+normalization	O
+,	O
+with	O
+Primer3	O
+software	O
+[	O
+76	O
+]	O
+and	O
+the	O
+sequence	O
+for	O
+each	O
+primer	O
+pair	O
+is	O
+shown	O
+in	O
+Table	O
+3	O
+.	O
+
+The	O
+Quantitect	O
+(	O
+TM	O
+)	O
+SYBR	O
+(	O
+R	O
+)	O
+Green	O
+RT	O
+-	O
+PCR	O
+kit	O
+(	O
+Qiagen	O
+)	O
+was	O
+used	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+except	O
+the	O
+final	O
+PCR	O
+volume	O
+was	O
+reduced	O
+to	O
+25	O
+mu	O
+l	O
+.	O
+
+The	O
+PCR	O
+conditions	O
+used	O
+on	O
+a	O
+Chromo4	O
+Real	O
+Time	O
+PCR	O
+Detection	O
+System	O
+(	O
+Bio	O
+-	O
+Rad	O
+,	O
+Hercules	O
+,	O
+CA	O
+)	O
+were	O
+as	O
+follows	O
+:	O
+HotStarTaq	O
+DNA	O
+polymerase	O
+activation	O
+at	O
+95	O
+degrees	O
+C	O
+for	O
+15	O
+min	O
+,	O
+45	O
+cycles	O
+of	O
+15	O
+s	O
+denaturation	O
+at	O
+94	O
+degrees	O
+C	O
+,	O
+30	O
+s	O
+annealing	O
+at	O
+58	O
+degrees	O
+C	O
+,	O
+30	O
+s	O
+extension	O
+at	O
+72	O
+degrees	O
+C	O
+,	O
+followed	O
+by	O
+a	O
+melting	O
+curve	O
+to	O
+ensure	O
+that	O
+a	O
+single	O
+PCR	O
+product	O
+was	O
+produced	O
+for	O
+each	O
+reaction	O
+.	O
+
+For	O
+each	O
+gene	O
+,	O
+the	O
+relative	O
+amount	O
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+gene	O
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+was	O
+calculated	O
+using	O
+the	O
+Delta	O
+Delta	O
+CT	O
+method	O
+[	O
+77	O
+]	O
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+significance	O
+was	O
+determined	O
+using	O
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+nonparametric	O
+Mann	O
+-	O
+Whitney	O
+U	O
+test	O
+and	O
+multiple	O
+linear	O
+regression	O
+in	O
+JMP	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+MRB	O
+participated	O
+in	O
+study	O
+conception	O
+and	O
+design	O
+,	O
+conducted	O
+gene	O
+expression	O
+experiments	O
+and	O
+data	O
+analysis	O
+,	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+ABW	O
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+in	O
+study	O
+design	O
+,	O
+data	O
+analysis	O
+,	O
+and	O
+manuscript	O
+revision	O
+.	O
+
+RPH	O
+and	O
+BPM	O
+participated	O
+in	O
+study	O
+conception	O
+and	O
+design	O
+,	O
+supervision	O
+of	O
+research	O
+activities	O
+,	O
+and	O
+manuscript	O
+revision	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+The	O
+comparative	O
+analysis	O
+of	O
+statistics	O
+,	O
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+on	O
+the	O
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+ratio	O
+criterion	O
+,	O
+in	O
+the	O
+automated	O
+annotation	O
+problem	O
+
+Abstract	O
+
+Background	O
+
+This	O
+paper	O
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+automated	O
+annotation	O
+.	O
+
+It	O
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+continuation	O
+of	O
+the	O
+previous	O
+work	O
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+-	O
+algorithm	O
+(	O
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+algorithm	O
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+automated	O
+annotation	O
+)	O
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+others	O
+.	O
+
+Results	O
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+A	O
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+annotation	O
+of	O
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+sequences	O
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+.	O
+
+All	O
+these	O
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+on	O
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+likelihood	O
+ratio	O
+criterion	O
+.	O
+
+Conclusion	O
+
+Some	O
+of	O
+the	O
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+a	O
+prediction	O
+quality	O
+that	O
+is	O
+significantly	O
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+(	O
+up	O
+to	O
+1	O
+.	O
+5	O
+times	O
+higher	O
+)	O
+in	O
+comparison	O
+with	O
+the	O
+results	O
+obtained	O
+with	O
+the	O
+A4	O
+-	O
+procedure	O
+.	O
+
+Background	O
+
+Many	O
+biological	O
+databanks	O
+,	O
+both	O
+dealing	O
+with	O
+protein	O
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+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+SWISS	O
+-	O
+PROT	O
+)	O
+and	O
+nucleotide	O
+sequences	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+GeneBank	O
+)	O
+,	O
+contain	O
+not	O
+only	O
+primary	O
+structures	O
+of	O
+sequences	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+sequences	O
+of	O
+letters	O
+-	O
+amino	O
+acids	O
+or	O
+nucleotides	O
+)	O
+,	O
+but	O
+also	O
+information	O
+about	O
+functions	O
+and	O
+properties	O
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+these	O
+sequences	O
+.	O
+
+This	O
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+is	O
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+so	O
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+
+There	O
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+-	O
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+(	O
+KeyWords	O
+)	O
+,	O
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+(	O
+Descriptions	O
+)	O
+,	O
+.	O
+.	O
+.	O
+,	O
+FT	O
+(	O
+Feature	O
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+)	O
+,	O
+.	O
+.	O
+.	O
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+.	O
+
+Words	O
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+,	O
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+,	O
+.	O
+.	O
+.	O
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+,	O
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+(	O
+letters	O
+)	O
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+
+The	O
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+
+Consider	O
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+(	O
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+)	O
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+(	O
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+.	O
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+)	O
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+properties	O
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+,	O
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+)	O
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+
+The	O
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+properties	O
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+(	O
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+,	O
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+restore	O
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+)	O
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+
+The	O
+annotation	O
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+
+This	O
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+paper	O
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+
+There	O
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+to	O
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+
+In	O
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+first	O
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+(	O
+it	O
+can	O
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+)	O
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+(	O
+grouping	O
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+/	O
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+)	O
+,	O
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+,	O
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+(	O
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+)	O
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+,	O
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+/	O
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+.	O
+
+An	O
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+.	O
+
+Fleischmann	O
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+.	O
+
+[	O
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+,	O
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+(	O
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+1000	O
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+)	O
+,	O
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+
+The	O
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+(	O
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+)	O
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+Instead	O
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+,	O
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+One	O
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+
+Andrade	O
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+
+[	O
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+
+In	O
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+
+In	O
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+,	O
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+,	O
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+
+The	O
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+
+This	O
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+(	O
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+Algorithm	O
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+
+The	O
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+
+More	O
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+,	O
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+
+Transfer	O
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+)	O
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+
+Transfer	O
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+
+For	O
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+
+In	O
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+
+All	O
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+(	O
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+)	O
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+
+As	O
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+,	O
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+.	O
+
+Two	O
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+
+A	O
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+
+The	O
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+-	O
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+
+The	O
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+
+Of	O
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+,	O
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+
+That	O
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+
+However	O
+,	O
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+"	O
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+"	O
+,	O
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+"	O
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+"	O
+.	O
+
+Obviously	O
+,	O
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+"	O
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+"	O
+
+Results	O
+
+Algorithm	O
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+
+Generation	O
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+a	O
+collection	O
+of	O
+similar	O
+sequences	O
+
+First	O
+,	O
+we	O
+introduce	O
+some	O
+notation	O
+.	O
+
+For	O
+the	O
+sake	O
+of	O
+brevity	O
+we	O
+write	O
+"	O
+a	O
+word	O
+omega	O
+belongs	O
+to	O
+a	O
+sequence	O
+pi	O
+"	O
+instead	O
+of	O
+"	O
+a	O
+word	O
+omega	O
+belongs	O
+to	O
+description	O
+fields	O
+of	O
+a	O
+sequence	O
+pi	O
+"	O
+.	O
+
+If	O
+omega	O
+is	O
+a	O
+KW	O
+-	O
+type	O
+word	O
+(	O
+to	O
+be	O
+definite	O
+,	O
+further	O
+in	O
+the	O
+paper	O
+we	O
+consider	O
+only	O
+amino	O
+-	O
+acid	O
+sequences	O
+and	O
+KW	O
+-	O
+type	O
+words	O
+)	O
+,	O
+we	O
+write	O
+omega	O
+in	O
+KW	O
+[	O
+pi	O
+]	O
+.	O
+
+The	O
+application	O
+of	O
+an	O
+annotation	O
+procedure	O
+to	O
+an	O
+unannotated	O
+amino	O
+-	O
+acid	O
+query	O
+sequence	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+prediction	O
+of	O
+description	O
+fields	O
+)	O
+starts	O
+with	O
+generating	O
+a	O
+collection	O
+of	O
+sequences	O
+similar	O
+to	O
+this	O
+query	O
+sequence	O
+with	O
+known	O
+description	O
+fields	O
+.	O
+
+These	O
+similar	O
+sequences	O
+are	O
+selected	O
+from	O
+a	O
+certain	O
+databank	O
+that	O
+contains	O
+annotated	O
+amino	O
+-	O
+acid	O
+sequences	O
+,	O
+e	O
+.	O
+g	O
+.	O
+,	O
+SWISS	O
+-	O
+PROT	O
+.	O
+
+There	O
+exist	O
+different	O
+approaches	O
+to	O
+the	O
+generation	O
+of	O
+a	O
+collection	O
+of	O
+similar	O
+sequences	O
+(	O
+see	O
+[	O
+7	O
+]	O
+)	O
+.	O
+
+This	O
+collections	O
+can	O
+be	O
+generated	O
+on	O
+the	O
+basis	O
+of	O
+global	O
+alignments	O
+between	O
+a	O
+query	O
+sequence	O
+and	O
+bank	O
+sequences	O
+(	O
+global	O
+alignments	O
+can	O
+be	O
+constructed	O
+,	O
+e	O
+.	O
+g	O
+.	O
+,	O
+by	O
+CLUSTAL	O
+procedure	O
+)	O
+using	O
+an	O
+identity	O
+percentage	O
+or	O
+,	O
+more	O
+generally	O
+,	O
+a	O
+similarity	O
+percentage	O
+as	O
+a	O
+similarity	O
+measure	O
+.	O
+
+Another	O
+variant	O
+is	O
+to	O
+use	O
+local	O
+alignments	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+alignments	O
+of	O
+most	O
+similar	O
+fragments	O
+of	O
+compared	O
+sequences	O
+,	O
+see	O
+[	O
+7	O
+]	O
+)	O
+instead	O
+of	O
+global	O
+alignments	O
+.	O
+
+Local	O
+alignments	O
+can	O
+be	O
+constructed	O
+,	O
+for	O
+example	O
+,	O
+by	O
+a	O
+well	O
+-	O
+known	O
+BLAST	O
+procedure	O
+[	O
+7	O
+,	O
+8	O
+]	O
+,	O
+in	O
+which	O
+sum	O
+of	O
+weights	O
+or	O
+a	O
+corresponding	O
+e	O
+-	O
+value	O
+serves	O
+as	O
+a	O
+measure	O
+of	O
+similarity	O
+between	O
+fragments	O
+(	O
+and	O
+thus	O
+between	O
+compared	O
+sequences	O
+)	O
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+
+Other	O
+alignment	O
+procedures	O
+are	O
+also	O
+acceptable	O
+;	O
+alignment	O
+procedure	O
+selection	O
+does	O
+not	O
+play	O
+a	O
+critical	O
+role	O
+.	O
+
+Since	O
+we	O
+build	O
+on	O
+the	O
+A4	O
+procedure	O
+,	O
+we	O
+briefly	O
+summarize	O
+that	O
+approach	O
+.	O
+
+In	O
+the	O
+A4	O
+procedure	O
+a	O
+collection	O
+of	O
+similar	O
+sequences	O
+is	O
+generated	O
+on	O
+the	O
+basis	O
+of	O
+local	O
+alignments	O
+of	O
+a	O
+special	O
+type	O
+.	O
+
+These	O
+alignments	O
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+constructed	O
+by	O
+the	O
+DotHelix	O
+procedure	O
+(	O
+[	O
+9	O
+]	O
+)	O
+,	O
+in	O
+which	O
+the	O
+"	O
+power	O
+"	O
+(	O
+sum	O
+of	O
+weights	O
+divided	O
+by	O
+the	O
+root	O
+of	O
+the	O
+length	O
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+,	O
+see	O
+[	O
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+.	O
+
+Each	O
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+located	O
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+
+Local	O
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+Each	O
+sequence	O
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+Let	O
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+(	O
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+The	O
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+constitute	O
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+i	O
+can	O
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+We	O
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+The	O
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+,	O
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+The	O
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+Let	O
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+xi	O
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+=	O
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+=	O
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+we	O
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+xi	O
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+=	O
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+Variables	O
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+In	O
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+Measures	O
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+Let	O
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+Statistical	O
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+The	O
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+
+It	O
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+ratio	O
+;	O
+total	O
+number	O
+of	O
+errors	O
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+(	O
+theoretically	O
+)	O
+be	O
+minimal	O
+for	O
+this	O
+threshold	O
+.	O
+
+Surely	O
+,	O
+the	O
+assumption	O
+that	O
+the	O
+ratio	O
+of	O
+a	O
+priori	O
+hypothesis	O
+probabilities	O
+equals	O
+1	O
+does	O
+not	O
+seem	O
+to	O
+be	O
+natural	O
+.	O
+
+Indeed	O
+,	O
+the	O
+number	O
+of	O
+considered	O
+words	O
+that	O
+do	O
+not	O
+belong	O
+to	O
+a	O
+query	O
+sequence	O
+is	O
+much	O
+greater	O
+(	O
+approximately	O
+8	O
+times	O
+greater	O
+)	O
+than	O
+the	O
+number	O
+of	O
+considered	O
+words	O
+that	O
+belong	O
+to	O
+a	O
+query	O
+sequence	O
+.	O
+
+But	O
+statistics	O
+that	O
+are	O
+obtained	O
+from	O
+the	O
+assumption	O
+that	O
+this	O
+a	O
+priori	O
+ratio	O
+equals	O
+1	O
+,	O
+and	O
+the	O
+assumption	O
+that	O
+this	O
+a	O
+priori	O
+ratio	O
+does	O
+not	O
+equal	O
+1	O
+,	O
+but	O
+is	O
+constant	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+it	O
+does	O
+not	O
+depend	O
+on	O
+a	O
+word	O
+omega	O
+)	O
+are	O
+equivalent	O
+.	O
+
+Essentially	O
+these	O
+are	O
+the	O
+same	O
+statistics	O
+(	O
+only	O
+the	O
+threshold	O
+value	O
+should	O
+be	O
+changed	O
+:	O
+a	O
+value	O
+P	O
+{	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+P	O
+{	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+should	O
+be	O
+taken	O
+instead	O
+of	O
+1	O
+;	O
+as	O
+it	O
+was	O
+noted	O
+,	O
+this	O
+value	O
+approximately	O
+equals	O
+8	O
+in	O
+our	O
+data	O
+)	O
+.	O
+
+Therefore	O
+,	O
+we	O
+assume	O
+from	O
+now	O
+on	O
+that	O
+the	O
+ratio	O
+of	O
+a	O
+priori	O
+hypothesis	O
+probabilities	O
+equals	O
+1	O
+.	O
+
+Thus	O
+all	O
+considered	O
+statistics	O
+are	O
+based	O
+on	O
+the	O
+likelihood	O
+ratio	O
+
+(	O
+1	O
+)	O
+P	O
+{	O
+xi	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+P	O
+{	O
+xi	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+
+Assumption	O
+of	O
+independence	O
+of	O
+variables	O
+xi	O
+i	O
+.	O
+
+Transfer	O
+probabilities	O
+
+By	O
+virtue	O
+of	O
+equation	O
+(	O
+1	O
+)	O
+we	O
+need	O
+to	O
+estimate	O
+conditional	O
+probabilities	O
+P	O
+{	O
+xi	O
+|	O
+xi	O
+0	O
+=	O
+epsilon	O
+}	O
+,	O
+where	O
+epsilon	O
+=	O
+1	O
+or	O
+0	O
+in	O
+order	O
+to	O
+calculate	O
+the	O
+likelihood	O
+ratio	O
+.	O
+
+Our	O
+derivation	O
+of	O
+these	O
+estimates	O
+uses	O
+the	O
+assumption	O
+that	O
+variables	O
+xi	O
+i	O
+,	O
+i	O
+=	O
+1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+n	O
+,	O
+are	O
+independent	O
+in	O
+the	O
+aggregate	O
+.	O
+
+Surely	O
+,	O
+this	O
+assumption	O
+is	O
+false	O
+.	O
+
+In	O
+reality	O
+variables	O
+xi	O
+i	O
+are	O
+dependent	O
+,	O
+and	O
+the	O
+dependence	O
+is	O
+considerably	O
+strong	O
+.	O
+
+Nevertheless	O
+,	O
+in	O
+our	O
+definition	O
+of	O
+the	O
+likelihood	O
+ratio	O
+statistic	O
+(	O
+and	O
+the	O
+statistic	O
+that	O
+is	O
+the	O
+logarithm	O
+of	O
+the	O
+likelihood	O
+ratio	O
+)	O
+we	O
+use	O
+the	O
+independence	O
+assumption	O
+.	O
+
+Since	O
+variables	O
+xi	O
+i	O
+are	O
+not	O
+independent	O
+,	O
+one	O
+can	O
+not	O
+assert	O
+that	O
+the	O
+obtained	O
+statistics	O
+are	O
+the	O
+most	O
+powerful	O
+,	O
+but	O
+these	O
+statistics	O
+can	O
+be	O
+still	O
+quite	O
+good	O
+.	O
+
+In	O
+decision	O
+theory	O
+,	O
+this	O
+approach	O
+is	O
+known	O
+as	O
+the	O
+naive	O
+Bayes	O
+procedure	O
+.	O
+
+The	O
+independence	O
+of	O
+variables	O
+xi	O
+i	O
+implies	O
+the	O
+equality	O
+
+(	O
+2	O
+)	O
+P	O
+{	O
+xi	O
+|	O
+xi	O
+0	O
+=	O
+epsilon	O
+}	O
+=	O
+product	O
+i	O
+=	O
+1nP	O
+{	O
+xi	O
+i	O
+|	O
+xi	O
+0	O
+=	O
+epsilon	O
+}	O
+,	O
+epsilon	O
+=	O
+1	O
+,	O
+0	O
+
+Each	O
+variable	O
+xi	O
+i	O
+has	O
+exactly	O
+two	O
+possible	O
+values	O
+:	O
+1	O
+and	O
+0	O
+.	O
+
+Thus	O
+,	O
+everything	O
+is	O
+reduced	O
+to	O
+the	O
+following	O
+four	O
+conditional	O
+probabilities	O
+:	O
+
+(	O
+3	O
+)	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+,	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+0	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+,	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+,	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+0	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+.	O
+
+In	O
+addition	O
+,	O
+it	O
+is	O
+clear	O
+that	O
+
+(	O
+4	O
+)	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
++	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+0	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+=	O
+1	O
+,	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
++	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+0	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+=	O
+1	O
+,	O
+
+so	O
+actually	O
+everything	O
+is	O
+reduced	O
+to	O
+two	O
+conditional	O
+probabilities	O
+
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+,	O
+P	O
+{	O
+xi	O
+i	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+.	O
+
+Conditional	O
+probabilities	O
+(	O
+3	O
+)	O
+are	O
+a	O
+special	O
+case	O
+of	O
+conditional	O
+probabilities	O
+of	O
+the	O
+type	O
+
+P	O
+{	O
+xi	O
+i	O
+=	O
+epsilon	O
+1	O
+|	O
+xi	O
+j	O
+=	O
+epsilon	O
+2	O
+}	O
+,	O
+where	O
+epsilon	O
+1	O
+,	O
+epsilon	O
+2	O
+=	O
+1	O
+or	O
+0	O
+,	O
+i	O
+,	O
+j	O
+=	O
+0	O
+,	O
+1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+n	O
+
+(	O
+above	O
+special	O
+case	O
+corresponds	O
+to	O
+j	O
+=	O
+0	O
+)	O
+.	O
+
+We	O
+call	O
+all	O
+this	O
+conditional	O
+probabilities	O
+transfer	O
+probabilities	O
+and	O
+denote	O
+them	O
+by	O
+
+P	O
+{	O
+xi	O
+i	O
+=	O
+epsilon	O
+1	O
+|	O
+xi	O
+j	O
+=	O
+epsilon	O
+2	O
+}	O
+=	O
+p	O
+epsilon	O
+1	O
+|	O
+epsilon	O
+2	O
+.	O
+
+Transfer	O
+probabilities	O
+depend	O
+on	O
+i	O
+,	O
+j	O
+(	O
+and	O
+certainly	O
+on	O
+the	O
+word	O
+omega	O
+)	O
+:	O
+
+p	O
+epsilon	O
+1	O
+|	O
+epsilon	O
+2	O
+=	O
+p	O
+epsilon	O
+1	O
+|	O
+epsilon	O
+2	O
+(	O
+i	O
+,	O
+j	O
+;	O
+omega	O
+)	O
+.	O
+
+Conditional	O
+probabilities	O
+play	O
+a	O
+central	O
+role	O
+in	O
+our	O
+procedure	O
+.	O
+
+According	O
+to	O
+equation	O
+(	O
+4	O
+)	O
+,	O
+it	O
+suffices	O
+to	O
+explain	O
+how	O
+transfer	O
+probabilities	O
+p1	O
+|	O
+1	O
+,	O
+p1	O
+|	O
+0	O
+are	O
+evaluated	O
+.	O
+
+We	O
+suppose	O
+that	O
+transfer	O
+probabilities	O
+satisfy	O
+the	O
+following	O
+assumptions	O
+(	O
+"	O
+axioms	O
+"	O
+)	O
+(	O
+the	O
+sense	O
+of	O
+these	O
+assumptions	O
+is	O
+obvious	O
+)	O
+.	O
+
+Assumption	O
+1	O
+)	O
+For	O
+a	O
+fixed	O
+word	O
+omega	O
+and	O
+for	O
+sequences	O
+pi	O
+0	O
+,	O
+pi	O
+1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+pi	O
+n	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+for	O
+the	O
+sequence	O
+pi	O
+0	O
+and	O
+sequences	O
+similar	O
+to	O
+pi	O
+0	O
+)	O
+transfer	O
+probabilities	O
+depend	O
+only	O
+on	O
+the	O
+measure	O
+of	O
+similarity	O
+between	O
+sequences	O
+.	O
+
+Thus	O
+,	O
+we	O
+have	O
+:	O
+
+p1	O
+|	O
+1	O
+=	O
+p1	O
+|	O
+1	O
+(	O
+i	O
+,	O
+j	O
+;	O
+omega	O
+)	O
+=	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+ij	O
+;	O
+omega	O
+)	O
+=	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+ij	O
+)	O
+=	O
+1	O
+-	O
+p0	O
+|	O
+1	O
+(	O
+mu	O
+ij	O
+)	O
+,	O
+
+p1	O
+|	O
+0	O
+=	O
+p1	O
+|	O
+0	O
+(	O
+i	O
+,	O
+j	O
+;	O
+omega	O
+)	O
+=	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+ij	O
+;	O
+omega	O
+)	O
+=	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+ij	O
+)	O
+=	O
+1	O
+-	O
+p0	O
+|	O
+0	O
+(	O
+mu	O
+ij	O
+)	O
+,	O
+
+where	O
+mu	O
+ij	O
+is	O
+the	O
+measure	O
+of	O
+similarity	O
+between	O
+sequences	O
+pi	O
+i	O
+,	O
+pi	O
+j	O
+(	O
+i	O
+,	O
+j	O
+=	O
+0	O
+,	O
+1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+n	O
+)	O
+.	O
+
+Particularly	O
+,	O
+if	O
+one	O
+of	O
+these	O
+sequences	O
+is	O
+the	O
+query	O
+sequence	O
+pi	O
+0	O
+and	O
+mu	O
+j	O
+is	O
+the	O
+measure	O
+of	O
+similarity	O
+between	O
+pi	O
+j	O
+,	O
+pi	O
+0	O
+,	O
+we	O
+have	O
+
+(	O
+5	O
+)	O
+P	O
+{	O
+xi	O
+j	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+=	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+j	O
+)	O
+,	O
+P	O
+{	O
+xi	O
+j	O
+=	O
+1	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+=	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+j	O
+)	O
+.	O
+
+Assumption	O
+2	O
+)	O
+Transfer	O
+probabilities	O
+(	O
+for	O
+an	O
+arbitrary	O
+fixed	O
+word	O
+omega	O
+)	O
+depend	O
+on	O
+similarity	O
+measure	O
+mu	O
+monotonically	O
+:	O
+the	O
+probability	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+)	O
+increases	O
+(	O
+does	O
+not	O
+decrease	O
+)	O
+and	O
+the	O
+probability	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+)	O
+decreases	O
+(	O
+does	O
+not	O
+increase	O
+)	O
+as	O
+mu	O
+increases	O
+.	O
+
+Assumption	O
+3	O
+)	O
+The	O
+inequality	O
+
+(	O
+6	O
+)	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+)	O
+>	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+)	O
+
+always	O
+holds	O
+(	O
+if	O
+mu	O
+>	O
+0	O
+)	O
+.	O
+
+Transfer	O
+probabilities	O
+are	O
+evaluated	O
+on	O
+the	O
+basis	O
+of	O
+the	O
+measure	O
+of	O
+similarity	O
+between	O
+similar	O
+sequences	O
+for	O
+which	O
+it	O
+is	O
+known	O
+whether	O
+omega	O
+in	O
+KW	O
+[	O
+pi	O
+i	O
+]	O
+using	O
+the	O
+so	O
+called	O
+isotonic	O
+regression	O
+procedure	O
+(	O
+see	O
+[	O
+11	O
+]	O
+)	O
+.	O
+
+(	O
+In	O
+[	O
+5	O
+]	O
+this	O
+procedure	O
+was	O
+referred	O
+to	O
+as	O
+monotonization	O
+procedure	O
+)	O
+.	O
+
+Results	O
+of	O
+this	O
+procedure	O
+are	O
+piecewise	O
+-	O
+constant	O
+monotonous	O
+functions	O
+of	O
+the	O
+similarity	O
+measure	O
+mu	O
+that	O
+increase	O
+(	O
+do	O
+not	O
+decrease	O
+)	O
+for	O
+probabilities	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+)	O
+and	O
+decrease	O
+(	O
+do	O
+not	O
+increase	O
+)	O
+for	O
+probabilities	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+)	O
+.	O
+
+We	O
+briefly	O
+recall	O
+the	O
+isotonic	O
+regression	O
+problem	O
+.	O
+
+Let	O
+one	O
+have	O
+two	O
+number	O
+sets	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+a	O
+set	O
+of	O
+points	O
+in	O
+the	O
+plain	O
+)	O
+xi	O
+,	O
+yi	O
+,	O
+i	O
+=	O
+1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+n	O
+,	O
+for	O
+which	O
+x1	O
+<	O
+=	O
+x2	O
+<	O
+=	O
+.	O
+.	O
+.	O
+<	O
+=	O
+xn	O
+.	O
+
+The	O
+task	O
+is	O
+to	O
+find	O
+values	O
+z1	O
+,	O
+z2	O
+,	O
+.	O
+.	O
+.	O
+,	O
+zn	O
+,	O
+z1	O
+<	O
+=	O
+z2	O
+<	O
+=	O
+.	O
+.	O
+.	O
+<	O
+=	O
+zn	O
+,	O
+that	O
+minimize	O
+the	O
+deviation	O
+sum	O
+i	O
+=	O
+1n	O
+(	O
+zi	O
+-	O
+yi	O
+)	O
+2	O
+.	O
+
+This	O
+is	O
+the	O
+monotone	O
+-	O
+increasing	O
+isotonic	O
+regression	O
+problem	O
+.	O
+
+The	O
+monotone	O
+-	O
+decreasing	O
+isotonic	O
+regression	O
+problem	O
+is	O
+similar	O
+;	O
+the	O
+only	O
+difference	O
+is	O
+that	O
+here	O
+z1	O
+>	O
+=	O
+z2	O
+>	O
+=	O
+.	O
+.	O
+.	O
+>	O
+=	O
+zn	O
+.	O
+
+The	O
+isotonic	O
+regression	O
+procedure	O
+constructs	O
+a	O
+monotonic	O
+number	O
+sequence	O
+z1	O
+,	O
+.	O
+.	O
+.	O
+,	O
+zn	O
+(	O
+while	O
+in	O
+linear	O
+regression	O
+values	O
+of	O
+zi	O
+are	O
+linearly	O
+expressed	O
+in	O
+terms	O
+of	O
+xi	O
+:	O
+zi	O
+=	O
+alpha	O
+xi	O
++	O
+beta	O
+)	O
+.	O
+
+An	O
+algorithm	O
+for	O
+the	O
+solution	O
+of	O
+isotonic	O
+regression	O
+problem	O
+can	O
+be	O
+easily	O
+constructed	O
+.	O
+
+We	O
+do	O
+not	O
+describe	O
+it	O
+here	O
+.	O
+
+We	O
+only	O
+note	O
+that	O
+each	O
+zi	O
+is	O
+the	O
+mean	O
+value	O
+of	O
+{	O
+yj	O
+}	O
+over	O
+a	O
+window	O
+of	O
+variable	O
+length	O
+:	O
+Li	O
+:	O
+zi	O
+=	O
+(	O
+sum	O
+j	O
+=	O
+t	O
+(	O
+i	O
+)	O
+t	O
+(	O
+i	O
+)	O
++	O
+L	O
+(	O
+i	O
+)	O
+-	O
+1yi	O
+)	O
+/	O
+Li	O
+.	O
+
+For	O
+different	O
+indices	O
+these	O
+windows	O
+either	O
+coincide	O
+or	O
+do	O
+not	O
+overlap	O
+,	O
+and	O
+the	O
+i	O
+-	O
+th	O
+window	O
+contains	O
+i	O
+.	O
+
+We	O
+also	O
+note	O
+that	O
+the	O
+values	O
+of	O
+xi	O
+are	O
+not	O
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+problem	O
+,	O
+only	O
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+order	O
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+values	O
+of	O
+yi	O
+is	O
+essential	O
+.	O
+
+To	O
+obtain	O
+the	O
+transfer	O
+probabilities	O
+using	O
+isotonic	O
+regression	O
+we	O
+proceed	O
+as	O
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+
+For	O
+the	O
+evaluation	O
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+|	O
+1	O
+we	O
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+sequences	O
+pi	O
+i	O
+,	O
+pi	O
+j	O
+that	O
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+the	O
+condition	O
+omega	O
+in	O
+KW	O
+[	O
+pi	O
+i	O
+]	O
+.	O
+
+Let	O
+mu	O
+ij	O
+denote	O
+the	O
+measure	O
+of	O
+similarity	O
+between	O
+sequences	O
+pi	O
+i	O
+,	O
+pi	O
+j	O
+.	O
+
+We	O
+put	O
+xi	O
+ij	O
+=	O
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+if	O
+the	O
+word	O
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+,	O
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+put	O
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+=	O
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+(	O
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+)	O
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+
+Then	O
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+-	O
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+
+The	O
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+|	O
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+(	O
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+)	O
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+
+Similarly	O
+,	O
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+the	O
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+-	O
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+,	O
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+,	O
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+|	O
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+|	O
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+(	O
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+)	O
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+
+Therefore	O
+,	O
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+|	O
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+,	O
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+|	O
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+Hence	O
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+In	O
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+Statistics	O
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+Let	O
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+(	O
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+(	O
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+-	O
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+,	O
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+
+The	O
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+,	O
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+in	O
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+annotation	O
+procedure	O
+,	O
+starts	O
+from	O
+a	O
+linear	O
+combination	O
+eta	O
+=	O
+sum	O
+i	O
+=	O
+1nai	O
+xi	O
+i	O
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+the	O
+xi	O
+i	O
+as	O
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+formula	O
+(	O
+12	O
+)	O
+.	O
+
+Here	O
+coefficients	O
+alpha	O
+i	O
+are	O
+not	O
+necessarily	O
+given	O
+by	O
+(	O
+13	O
+)	O
+,	O
+but	O
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+be	O
+positive	O
+and	O
+satisfy	O
+the	O
+relation	O
+(	O
+14	O
+)	O
+.	O
+
+This	O
+approach	O
+uses	O
+the	O
+assumption	O
+that	O
+eta	O
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+the	O
+normal	O
+distribution	O
+.	O
+
+Certainly	O
+this	O
+assumption	O
+is	O
+not	O
+correct	O
+(	O
+at	O
+least	O
+because	O
+the	O
+inequality	O
+0	O
+<	O
+=	O
+eta	O
+<	O
+=	O
+1	O
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+)	O
+.	O
+
+Nevertheless	O
+,	O
+we	O
+use	O
+this	O
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+(	O
+and	O
+,	O
+similarly	O
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+,	O
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+xi	O
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+(	O
+omega	O
+)	O
+)	O
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+
+(	O
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+the	O
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+continuous	O
+,	O
+this	O
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+"	O
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+"	O
+)	O
+.	O
+
+Thus	O
+,	O
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+
+(	O
+15	O
+)	O
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+=	O
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+i	O
+=	O
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+
+and	O
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+
+Denote	O
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+
+M1	O
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+=	O
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+|	O
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+=	O
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+)	O
+,	O
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+=	O
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+(	O
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+|	O
+xi	O
+0	O
+=	O
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+)	O
+=	O
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+,	O
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+=	O
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+|	O
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+0	O
+=	O
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+)	O
+,	O
+D0	O
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+=	O
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+(	O
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+|	O
+xi	O
+0	O
+=	O
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+)	O
+=	O
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+02	O
+
+the	O
+conditional	O
+expectations	O
+and	O
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+of	O
+eta	O
+given	O
+that	O
+xi	O
+0	O
+=	O
+1	O
+or	O
+0	O
+respectively	O
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+
+We	O
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+
+M1	O
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+=	O
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+(	O
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+|	O
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+=	O
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+)	O
+=	O
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+|	O
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+(	O
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+)	O
+,	O
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+=	O
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+|	O
+0	O
+(	O
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+)	O
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+
+Further	O
+,	O
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+of	O
+xi	O
+i	O
+(	O
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+)	O
+implies	O
+that	O
+
+D1	O
+eta	O
+=	O
+sigma	O
+12	O
+=	O
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+iai2	O
+.	O
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+|	O
+1	O
+(	O
+mu	O
+i	O
+)	O
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+(	O
+1	O
+-	O
+p1	O
+|	O
+1	O
+(	O
+mu	O
+i	O
+)	O
+)	O
+,	O
+D0	O
+eta	O
+=	O
+sigma	O
+02	O
+=	O
+sum	O
+iai2	O
+.	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+i	O
+)	O
+.	O
+(	O
+1	O
+-	O
+p1	O
+|	O
+0	O
+(	O
+mu	O
+i	O
+)	O
+)	O
+.	O
+
+(	O
+We	O
+note	O
+that	O
+it	O
+is	O
+the	O
+only	O
+place	O
+where	O
+the	O
+independence	O
+of	O
+xi	O
+i	O
+is	O
+used	O
+;	O
+therefore	O
+,	O
+the	O
+assumption	O
+of	O
+independence	O
+of	O
+xi	O
+i	O
+is	O
+not	O
+as	O
+essential	O
+in	O
+this	O
+approach	O
+as	O
+it	O
+was	O
+in	O
+the	O
+definition	O
+of	O
+the	O
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+T	O
+(	O
+1	O
+)	O
+)	O
+.	O
+
+It	O
+follows	O
+from	O
+the	O
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+of	O
+a	O
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+that	O
+in	O
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+xi	O
+0	O
+=	O
+1	O
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+0	O
+the	O
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+
+(	O
+16	O
+)	O
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+-	O
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+1	O
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+-	O
+M0	O
+eta	O
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+0	O
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+standard	O
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+distribution	O
+N	O
+(	O
+0	O
+,	O
+1	O
+)	O
+
+As	O
+above	O
+,	O
+we	O
+use	O
+the	O
+logarithm	O
+of	O
+the	O
+likelihood	O
+ratio	O
+as	O
+a	O
+statistic	O
+and	O
+in	O
+addition	O
+assume	O
+that	O
+the	O
+ratio	O
+of	O
+a	O
+priori	O
+hypothesis	O
+probabilities	O
+is	O
+equal	O
+to	O
+1	O
+.	O
+
+Let	O
+us	O
+denote	O
+this	O
+statistic	O
+by	O
+T	O
+(	O
+2	O
+)	O
+.	O
+
+Relation	O
+(	O
+16	O
+)	O
+implies	O
+that	O
+
+T	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+=	O
+ln	O
+P	O
+{	O
+lambda	O
+<	O
+=	O
+eta	O
+<	O
+=	O
+lambda	O
++	O
+d	O
+lambda	O
+|	O
+xi	O
+0	O
+=	O
+1	O
+}	O
+P	O
+{	O
+lambda	O
+<	O
+=	O
+eta	O
+<	O
+=	O
+lambda	O
++	O
+d	O
+lambda	O
+|	O
+xi	O
+0	O
+=	O
+0	O
+}	O
+=	O
+ln	O
+(	O
+1	O
+/	O
+2	O
+pi	O
+.	O
+sigma	O
+1	O
+)	O
+.	O
+exp	O
+{	O
+-	O
+12	O
+.	O
+(	O
+(	O
+lambda	O
+-	O
+M1	O
+eta	O
+)	O
+/	O
+sigma	O
+1	O
+)	O
+2	O
+}	O
+(	O
+1	O
+/	O
+2	O
+pi	O
+.	O
+sigma	O
+0	O
+)	O
+.	O
+exp	O
+{	O
+12	O
+.	O
+(	O
+(	O
+lambda	O
+-	O
+M0	O
+eta	O
+)	O
+/	O
+sigma	O
+0	O
+)	O
+2	O
+}	O
+=	O
+12	O
+.	O
+{	O
+(	O
+(	O
+lambda	O
+-	O
+M0	O
+eta	O
+)	O
+/	O
+sigma	O
+0	O
+)	O
+2	O
+-	O
+(	O
+(	O
+lambda	O
+-	O
+M1	O
+eta	O
+)	O
+/	O
+sigma	O
+1	O
+)	O
+2	O
+}	O
++	O
+ln	O
+(	O
+sigma	O
+0	O
+/	O
+sigma	O
+1	O
+)	O
+.	O
+
+Another	O
+variant	O
+of	O
+this	O
+statistic	O
+-	O
+statistic	O
+T	O
+^	O
+(	O
+2	O
+)	O
+-	O
+was	O
+used	O
+in	O
+the	O
+paper	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+statistic	O
+T	O
+^	O
+(	O
+2	O
+)	O
+is	O
+the	O
+ratio	O
+of	O
+type	O
+1	O
+error	O
+to	O
+type	O
+2	O
+error	O
+:	O
+
+(	O
+17	O
+)	O
+T	O
+^	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+=	O
+ln	O
+P	O
+(	O
+1	O
+)	O
+(	O
+lambda	O
+)	O
+P	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+=	O
+ln	O
+Phi	O
+(	O
+(	O
+lambda	O
+-	O
+M1	O
+eta	O
+)	O
+/	O
+sigma	O
+1	O
+)	O
+1	O
+-	O
+Phi	O
+(	O
+(	O
+lambda	O
+-	O
+M0	O
+eta	O
+)	O
+/	O
+sigma	O
+0	O
+)	O
+,	O
+
+where	O
+Phi	O
+(	O
+x	O
+)	O
+is	O
+the	O
+cumulative	O
+normal	O
+distribution	O
+function	O
+:	O
+Phi	O
+(	O
+x	O
+)	O
+=	O
+12	O
+pi	O
+integral	O
+-	O
+infinity	O
+xe	O
+-	O
+z22dz	O
+.	O
+
+The	O
+statistics	O
+eta	O
+and	O
+T	O
+^	O
+(	O
+2	O
+)	O
+are	O
+equivalent	O
+for	O
+an	O
+arbitrary	O
+fixed	O
+word	O
+omega	O
+(	O
+although	O
+not	O
+equivalent	O
+for	O
+the	O
+whole	O
+totality	O
+of	O
+words	O
+)	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+,	O
+the	O
+statistics	O
+eta	O
+and	O
+T	O
+(	O
+2	O
+)	O
+are	O
+not	O
+necessarily	O
+equivalent	O
+,	O
+as	O
+the	O
+dependence	O
+of	O
+T	O
+(	O
+2	O
+)	O
+on	O
+eta	O
+may	O
+turn	O
+out	O
+to	O
+be	O
+not	O
+monotonic	O
+.	O
+
+Moreover	O
+,	O
+it	O
+is	O
+never	O
+monotonic	O
+for	O
+all	O
+values	O
+of	O
+eta	O
+.	O
+
+However	O
+,	O
+we	O
+are	O
+interested	O
+only	O
+in	O
+values	O
+0	O
+<	O
+=	O
+eta	O
+<	O
+=	O
+1	O
+,	O
+and	O
+usually	O
+(	O
+though	O
+not	O
+always	O
+)	O
+the	O
+dependence	O
+of	O
+T	O
+(	O
+2	O
+)	O
+on	O
+eta	O
+is	O
+monotonous	O
+for	O
+these	O
+values	O
+of	O
+eta	O
+,	O
+and	O
+in	O
+this	O
+case	O
+the	O
+statistics	O
+eta	O
+and	O
+T	O
+(	O
+2	O
+)	O
+are	O
+equivalent	O
+(	O
+for	O
+a	O
+fixed	O
+word	O
+omega	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+even	O
+in	O
+the	O
+case	O
+where	O
+the	O
+dependence	O
+is	O
+not	O
+monotonic	O
+,	O
+the	O
+monotonicity	O
+is	O
+violated	O
+only	O
+for	O
+the	O
+values	O
+of	O
+eta	O
+close	O
+either	O
+to	O
+0	O
+or	O
+to	O
+1	O
+,	O
+and	O
+the	O
+lack	O
+of	O
+monotonicity	O
+can	O
+be	O
+disregarded	O
+.	O
+
+We	O
+still	O
+have	O
+to	O
+discuss	O
+the	O
+question	O
+of	O
+the	O
+choice	O
+of	O
+coefficients	O
+ai	O
+in	O
+(	O
+15	O
+)	O
+.	O
+
+One	O
+of	O
+the	O
+variants	O
+was	O
+described	O
+above	O
+:	O
+formula	O
+(	O
+13	O
+)	O
+can	O
+be	O
+applied	O
+.	O
+
+Another	O
+variant	O
+was	O
+introduced	O
+in	O
+[	O
+5	O
+]	O
+.	O
+
+This	O
+variant	O
+can	O
+be	O
+described	O
+as	O
+follows	O
+.	O
+
+As	O
+above	O
+,	O
+we	O
+assume	O
+that	O
+the	O
+variate	O
+eta	O
+=	O
+sum	O
+ai	O
+xi	O
+i	O
+has	O
+a	O
+normal	O
+distribution	O
+.	O
+
+Each	O
+set	O
+of	O
+coefficients	O
+ai	O
+and	O
+each	O
+threshold	O
+value	O
+lambda	O
+have	O
+corresponding	O
+theoretical	O
+frequencies	O
+of	O
+type	O
+1	O
+and	O
+type	O
+2	O
+errors	O
+P	O
+(	O
+1	O
+)	O
+(	O
+lambda	O
+)	O
+,	O
+P	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+.	O
+
+The	O
+idea	O
+is	O
+to	O
+take	O
+the	O
+set	O
+of	O
+coefficients	O
+{	O
+ai	O
+}	O
+that	O
+gives	O
+the	O
+minimum	O
+sum	O
+P	O
+(	O
+1	O
+)	O
+(	O
+lambda	O
+)	O
++	O
+P	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+,	O
+where	O
+lambda	O
+is	O
+the	O
+best	O
+threshold	O
+value	O
+for	O
+this	O
+coefficient	O
+set	O
+.	O
+
+However	O
+,	O
+analytically	O
+it	O
+is	O
+very	O
+cumbersome	O
+,	O
+so	O
+the	O
+following	O
+simplification	O
+was	O
+implemented	O
+.	O
+
+For	O
+a	O
+fixed	O
+set	O
+of	O
+coefficients	O
+{	O
+ai	O
+}	O
+we	O
+select	O
+the	O
+threshold	O
+value	O
+lambda	O
+such	O
+that	O
+the	O
+frequency	O
+of	O
+type	O
+1	O
+errors	O
+is	O
+equal	O
+to	O
+the	O
+frequency	O
+of	O
+type	O
+2	O
+errors	O
+:	O
+P	O
+(	O
+1	O
+)	O
+(	O
+lambda	O
+)	O
+=	O
+P	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+.	O
+
+Then	O
+we	O
+find	O
+the	O
+set	O
+of	O
+coefficients	O
+that	O
+minimizes	O
+these	O
+frequencies	O
+P	O
+(	O
+1	O
+)	O
+(	O
+lambda	O
+)	O
+=	O
+P	O
+(	O
+2	O
+)	O
+(	O
+lambda	O
+)	O
+.	O
+
+Here	O
+the	O
+search	O
+of	O
+the	O
+coefficient	O
+set	O
+can	O
+be	O
+reduced	O
+to	O
+a	O
+conditional	O
+extremum	O
+problem	O
+.	O
+
+The	O
+A4	O
+algorithm	O
+uses	O
+an	O
+iterated	O
+procedure	O
+for	O
+the	O
+solution	O
+of	O
+this	O
+problem	O
+(	O
+see	O
+[	O
+5	O
+]	O
+)	O
+.	O
+
+In	O
+order	O
+to	O
+optimize	O
+the	O
+automated	O
+annotation	O
+procedure	O
+,	O
+that	O
+is	O
+to	O
+increase	O
+the	O
+prediction	O
+quality	O
+,	O
+certain	O
+modifications	O
+of	O
+the	O
+procedure	O
+were	O
+introduced	O
+.	O
+
+For	O
+each	O
+statistic	O
+(	O
+eta	O
+,	O
+T	O
+(	O
+1	O
+)	O
+,	O
+T	O
+(	O
+2	O
+)	O
+,	O
+T	O
+^	O
+(	O
+2	O
+)	O
+)	O
+many	O
+variants	O
+(	O
+up	O
+to	O
+36	O
+)	O
+,	O
+including	O
+the	O
+variant	O
+that	O
+was	O
+described	O
+above	O
+,	O
+were	O
+considered	O
+-	O
+each	O
+variant	O
+corresponds	O
+to	O
+a	O
+certain	O
+combination	O
+of	O
+these	O
+modifications	O
+.	O
+
+Some	O
+variants	O
+really	O
+turned	O
+out	O
+to	O
+be	O
+better	O
+than	O
+the	O
+variants	O
+described	O
+above	O
+.	O
+
+A	O
+simplified	O
+scheme	O
+of	O
+modifications	O
+(	O
+and	O
+thereby	O
+of	O
+statistic	O
+variants	O
+)	O
+can	O
+be	O
+described	O
+as	O
+follows	O
+.	O
+
+1	O
+)	O
+What	O
+primary	O
+local	O
+alignments	O
+are	O
+considered	O
+?	O
+
+In	O
+the	O
+described	O
+variant	O
+of	O
+statistics	O
+only	O
+one	O
+primary	O
+local	O
+alignment	O
+(	O
+the	O
+one	O
+with	O
+the	O
+maximum	O
+power	O
+)	O
+was	O
+considered	O
+.	O
+
+Meanwhile	O
+,	O
+all	O
+constructed	O
+local	O
+alignments	O
+with	O
+sufficiently	O
+high	O
+power	O
+can	O
+be	O
+considered	O
+,	O
+as	O
+it	O
+was	O
+done	O
+in	O
+[	O
+5	O
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+In	O
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+2	O
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+In	O
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+,	O
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+
+In	O
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+For	O
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+3	O
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+The	O
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+(	O
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+As	O
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+So	O
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+(	O
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+(	O
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+Finally	O
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+A	O
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+Here	O
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+We	O
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+,	O
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+
+Testing	O
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+Testing	O
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+A	O
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+,	O
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+,	O
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+Note	O
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+,	O
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+All	O
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+The	O
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+This	O
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+The	O
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+A	O
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+The	O
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+Then	O
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+All	O
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+
+Hence	O
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+
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+The	O
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+
+Final	O
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+Testing	O
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+The	O
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+Each	O
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+The	O
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+Variants	O
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+
+Recall	O
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+the	O
+statistic	O
+T	O
+^	O
+(	O
+2	O
+)	O
+[	O
+1	O
+,	O
+0	O
+]	O
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+exactly	O
+the	O
+statistic	O
+that	O
+was	O
+considered	O
+in	O
+[	O
+5	O
+]	O
+(	O
+note	O
+that	O
+it	O
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+the	O
+best	O
+variant	O
+for	O
+the	O
+statistic	O
+T	O
+^	O
+(	O
+2	O
+)	O
+)	O
+.	O
+
+The	O
+results	O
+could	O
+also	O
+have	O
+been	O
+presented	O
+as	O
+a	O
+confusion	O
+table	O
+as	O
+laid	O
+out	O
+in	O
+Table	O
+3	O
+,	O
+but	O
+doing	O
+so	O
+for	O
+all	O
+variants	O
+would	O
+take	O
+a	O
+lot	O
+of	O
+space	O
+.	O
+
+The	O
+testing	O
+results	O
+showed	O
+that	O
+the	O
+first	O
+modification	O
+(	O
+consideration	O
+of	O
+all	O
+primary	O
+local	O
+alignments	O
+or	O
+only	O
+one	O
+primary	O
+local	O
+alignment	O
+with	O
+the	O
+maximum	O
+power	O
+)	O
+did	O
+not	O
+significantly	O
+affect	O
+the	O
+prediction	O
+quality	O
+,	O
+so	O
+results	O
+are	O
+only	O
+presented	O
+for	O
+one	O
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+(	O
+all	O
+local	O
+alignments	O
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+considered	O
+,	O
+similarly	O
+to	O
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+5	O
+]	O
+)	O
+.	O
+
+Note	O
+that	O
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+results	O
+presented	O
+in	O
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+Table	O
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+to	O
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+whole	O
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+degenerate	O
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+(	O
+though	O
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+,	O
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+1	O
+)	O
+,	O
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+)	O
+,	O
+T	O
+^	O
+(	O
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+)	O
+,	O
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+)	O
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+non	O
+-	O
+degenerate	O
+words	O
+,	O
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+degenerate	O
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+basis	O
+of	O
+the	O
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+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+on	O
+the	O
+basis	O
+of	O
+word	O
+frequency	O
+)	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+total	O
+number	O
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+errors	O
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+errors	O
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+degenerate	O
+words	O
+.	O
+
+It	O
+is	O
+worth	O
+noticing	O
+that	O
+the	O
+total	O
+number	O
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+degenerate	O
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+case	O
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+choice	O
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+threshold	O
+q0	O
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+the	O
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+(	O
+omega	O
+)	O
+turned	O
+out	O
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+(	O
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+the	O
+whole	O
+totality	O
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+words	O
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+)	O
+;	O
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+included	O
+twelve	O
+type	O
+1	O
+errors	O
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+one	O
+type	O
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+(	O
+recall	O
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+the	O
+prediction	O
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+performed	O
+for	O
+2029	O
+degenerate	O
+words	O
+,	O
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+incorrect	O
+only	O
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+)	O
+.	O
+
+Such	O
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+small	O
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+seemingly	O
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+explained	O
+by	O
+the	O
+fact	O
+that	O
+for	O
+degenerate	O
+words	O
+the	O
+frequency	O
+q	O
+(	O
+omega	O
+)	O
+is	O
+nearly	O
+always	O
+close	O
+either	O
+to	O
+1	O
+or	O
+to	O
+0	O
+,	O
+otherwise	O
+in	O
+almost	O
+all	O
+cases	O
+transfer	O
+probabilities	O
+p1	O
+|	O
+1	O
+,	O
+p1	O
+|	O
+0	O
+can	O
+be	O
+defined	O
+for	O
+at	O
+least	O
+some	O
+values	O
+of	O
+similarity	O
+measure	O
+mu	O
+and	O
+hence	O
+a	O
+word	O
+omega	O
+turns	O
+out	O
+to	O
+be	O
+non	O
+-	O
+degenerate	O
+.	O
+
+We	O
+also	O
+note	O
+that	O
+along	O
+with	O
+type	O
+1	O
+and	O
+type	O
+2	O
+errors	O
+other	O
+errors	O
+can	O
+occur	O
+,	O
+as	O
+it	O
+is	O
+possible	O
+that	O
+some	O
+words	O
+from	O
+description	O
+fields	O
+of	O
+a	O
+query	O
+sequence	O
+do	O
+not	O
+belong	O
+to	O
+description	O
+fields	O
+of	O
+similar	O
+sequences	O
+and	O
+hence	O
+the	O
+prediction	O
+is	O
+not	O
+performed	O
+for	O
+these	O
+words	O
+at	O
+all	O
+.	O
+
+However	O
+,	O
+we	O
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+similar	O
+sequences	O
+(	O
+100	O
+)	O
+for	O
+the	O
+prediction	O
+,	O
+so	O
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+errors	O
+were	O
+extremely	O
+rare	O
+(	O
+only	O
+two	O
+words	O
+for	O
+the	O
+whole	O
+test	O
+set	O
+of	O
+518	O
+sequences	O
+,	O
+whereas	O
+the	O
+number	O
+of	O
+words	O
+for	O
+which	O
+the	O
+prediction	O
+was	O
+performed	O
+equaled	O
+9236	O
+)	O
+.	O
+
+Hence	O
+,	O
+in	O
+our	O
+case	O
+these	O
+errors	O
+can	O
+be	O
+disregarded	O
+.	O
+
+Statistical	O
+analysis	O
+showed	O
+that	O
+the	O
+precision	O
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+evaluation	O
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+,	O
+N2	O
+,	O
+Nall	O
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+reasonable	O
+:	O
+it	O
+can	O
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+checked	O
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+the	O
+relative	O
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+(	O
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+standard	O
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+ln	O
+(	O
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+)	O
+)	O
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+the	O
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+7	O
+-	O
+10	O
+%	O
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+is	O
+in	O
+line	O
+with	O
+the	O
+relative	O
+precision	O
+of	O
+a	O
+Poisson	O
+random	O
+variable	O
+that	O
+is	O
+given	O
+by	O
+1	O
+/	O
+Nall	O
+.	O
+
+However	O
+,	O
+since	O
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+"	O
+methods	O
+"	O
+(	O
+the	O
+statistics	O
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+their	O
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+)	O
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+same	O
+sequences	O
+,	O
+the	O
+standard	O
+error	O
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+the	O
+comparison	O
+between	O
+methods	O
+is	O
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+smaller	O
+due	O
+to	O
+the	O
+high	O
+correlation	O
+of	O
+results	O
+for	O
+the	O
+same	O
+sequence	O
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+is	O
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+the	O
+order	O
+of	O
+2	O
+-	O
+4	O
+%	O
+.	O
+
+This	O
+implies	O
+that	O
+"	O
+methods	O
+"	O
+for	O
+which	O
+Nall	O
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+be	O
+significantly	O
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+.	O
+
+This	O
+shows	O
+that	O
+size	O
+of	O
+the	O
+experiment	O
+with	O
+210	O
+randomly	O
+selected	O
+sequences	O
+in	O
+the	O
+learning	O
+stage	O
+and	O
+308	O
+sequences	O
+in	O
+the	O
+testing	O
+stage	O
+is	O
+large	O
+enough	O
+to	O
+obtain	O
+valid	O
+statements	O
+about	O
+the	O
+accuracy	O
+of	O
+the	O
+proposed	O
+methodology	O
+and	O
+allows	O
+statistical	O
+comparisons	O
+of	O
+different	O
+statistics	O
+and	O
+variants	O
+.	O
+
+When	O
+the	O
+set	O
+of	O
+tested	O
+sequences	O
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+fixed	O
+,	O
+the	O
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+number	O
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+objective	O
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+prediction	O
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+,	O
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+the	O
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+(	O
+selected	O
+during	O
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+"	O
+learning	O
+stage	O
+"	O
+)	O
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+minimum	O
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+total	O
+number	O
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+errors	O
+.	O
+
+However	O
+,	O
+if	O
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+testing	O
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+(	O
+based	O
+on	O
+different	O
+sets	O
+of	O
+query	O
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+)	O
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+compared	O
+,	O
+then	O
+absolute	O
+numbers	O
+of	O
+errors	O
+can	O
+not	O
+be	O
+treated	O
+as	O
+a	O
+procedure	O
+quality	O
+measure	O
+,	O
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+relative	O
+quantities	O
+(	O
+proportions	O
+)	O
+should	O
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+considered	O
+instead	O
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+absolute	O
+quantities	O
+.	O
+
+Usually	O
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+sum	O
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+the	O
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+)	O
++	O
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+(	O
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+)	O
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+presented	O
+in	O
+the	O
+fifth	O
+column	O
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+Table	O
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+.	O
+
+However	O
+,	O
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+-	O
+nq	O
+that	O
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+query	O
+sequences	O
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+larger	O
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+nq	O
+,	O
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+majority	O
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+these	O
+words	O
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+they	O
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+query	O
+sequence	O
+.	O
+
+Consequently	O
+,	O
+in	O
+case	O
+of	O
+optimal	O
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+)	O
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+,	O
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+)	O
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+
+Thus	O
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+(	O
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+)	O
++	O
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+)	O
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+our	O
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+(	O
+see	O
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+)	O
+.	O
+
+The	O
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+(	O
++	O
+)	O
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+the	O
+number	O
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+wrong	O
+positive	O
+predictions	O
+to	O
+the	O
+total	O
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+positive	O
+predictions	O
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+(	O
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+)	O
+.	O
+
+Hence	O
+,	O
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+)	O
++	O
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+(	O
++	O
+)	O
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+
+Exactly	O
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+[	O
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+]	O
+.	O
+
+In	O
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+decision	O
+making	O
+(	O
+diagnostic	O
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+)	O
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+(	O
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+=	O
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+)	O
+)	O
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+=	O
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+-	O
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+)	O
+)	O
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+accuracy	O
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+a	O
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+,	O
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+-	O
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++	O
+)	O
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+known	O
+as	O
+the	O
+positive	O
+predictive	O
+value	O
+.	O
+
+Alternative	O
+terminology	O
+is	O
+discussed	O
+in	O
+[	O
+12	O
+]	O
+.	O
+
+The	O
+ROC	O
+curve	O
+plotting	O
+sens	O
+against	O
+1	O
+-	O
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+is	O
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+popular	O
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+
+It	O
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+,	O
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+.	O
+
+Figure	O
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+.	O
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+,	O
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+variants	O
+that	O
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+Table	O
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+)	O
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+-	O
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+
+Discussion	O
+
+Overall	O
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+Mean	O
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+)	O
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+
+These	O
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+
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+)	O
+,	O
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+)	O
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+.	O
+
+For	O
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+)	O
+,	O
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+)	O
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+,	O
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+which	O
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+calculation	O
+of	O
+coefficients	O
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+(	O
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+)	O
+(	O
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+.	O
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+.	O
+,	O
+variants	O
+[	O
+0	O
+,	O
+0	O
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+[	O
+1	O
+,	O
+0	O
+]	O
+;	O
+recall	O
+that	O
+the	O
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+(	O
+1	O
+)	O
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+)	O
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+shows	O
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+(	O
+1	O
+)	O
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+better	O
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+T	O
+(	O
+2	O
+)	O
+.	O
+
+The	O
+same	O
+conclusion	O
+can	O
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+ROC	O
+curves	O
+presented	O
+in	O
+Fig	O
+.	O
+
+2	O
+.	O
+
+Testing	O
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+(	O
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+(	O
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+)	O
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+,	O
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+)	O
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+
+That	O
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+
+It	O
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+)	O
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+,	O
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+We	O
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+Recall	O
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+These	O
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+
+It	O
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+,	O
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+)	O
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+=	O
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+=	O
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+=	O
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+=	O
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+-	O
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+01	O
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+01	O
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+In	O
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+,	O
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+
+As	O
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+,	O
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+
+The	O
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+
+Since	O
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+,	O
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+(	O
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+.	O
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+,	O
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+(	O
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+)	O
+)	O
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+unrepresentative	O
+.	O
+
+In	O
+the	O
+same	O
+time	O
+,	O
+the	O
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+all	O
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+(	O
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+0	O
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+)	O
+.	O
+
+Consequently	O
+,	O
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+so	O
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+,	O
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+(	O
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+)	O
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+
+From	O
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+)	O
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+)	O
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+
+It	O
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+,	O
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+)	O
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+
+This	O
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+
+Since	O
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+test	O
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+,	O
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+,	O
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+.	O
+
+Effect	O
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+
+The	O
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+
+One	O
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+
+Thus	O
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+
+It	O
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+.	O
+
+At	O
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+
+Currently	O
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+(	O
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+)	O
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+
+Comparison	O
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+
+For	O
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+(	O
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+As	O
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+
+Furthermore	O
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+,	O
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+
+Such	O
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+
+et	O
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+
+[	O
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+
+This	O
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+
+It	O
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+=	O
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+,	O
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+,	O
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+=	O
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+In	O
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+,	O
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+
+That	O
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+
+The	O
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+
+The	O
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+Surprisingly	O
+,	O
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+(	O
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+
+It	O
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+
+We	O
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+
+It	O
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+in	O
+the	O
+literature	O
+.	O
+
+There	O
+is	O
+a	O
+similarity	O
+with	O
+the	O
+approach	O
+of	O
+Kajan	O
+et	O
+al	O
+.	O
+
+[	O
+15	O
+]	O
+.	O
+
+They	O
+also	O
+base	O
+their	O
+procedures	O
+on	O
+the	O
+likelihood	O
+ratio	O
+,	O
+but	O
+use	O
+approximations	O
+based	O
+on	O
+maximal	O
+similarity	O
+(	O
+or	O
+minimal	O
+distance	O
+)	O
+,	O
+while	O
+we	O
+attempt	O
+to	O
+estimate	O
+the	O
+likelihood	O
+ratio	O
+from	O
+pairwise	O
+comparisons	O
+within	O
+the	O
+set	O
+of	O
+similar	O
+sequences	O
+.	O
+
+There	O
+is	O
+also	O
+an	O
+interesting	O
+relation	O
+with	O
+the	O
+GOPET	O
+tool	O
+presented	O
+in	O
+[	O
+16	O
+]	O
+based	O
+on	O
+earlier	O
+work	O
+by	O
+the	O
+same	O
+authors	O
+[	O
+17	O
+]	O
+.	O
+
+These	O
+authors	O
+use	O
+a	O
+number	O
+of	O
+characteristics	O
+of	O
+the	O
+set	O
+of	O
+found	O
+similar	O
+sequences	O
+for	O
+term	O
+(	O
+word	O
+)	O
+,	O
+such	O
+as	O
+maximal	O
+e	O
+-	O
+value	O
+,	O
+frequency	O
+of	O
+the	O
+term	O
+etc	O
+.	O
+,	O
+as	O
+a	O
+coordinates	O
+of	O
+decision	O
+making	O
+space	O
+.	O
+
+They	O
+use	O
+more	O
+features	O
+while	O
+we	O
+concentrate	O
+on	O
+the	O
+similarity	O
+.	O
+
+That	O
+might	O
+be	O
+an	O
+advantage	O
+for	O
+their	O
+method	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+we	O
+try	O
+to	O
+use	O
+the	O
+information	O
+from	O
+all	O
+similar	O
+sequences	O
+in	O
+an	O
+optimal	O
+way	O
+relying	O
+on	O
+statistical	O
+decision	O
+theory	O
+by	O
+means	O
+of	O
+the	O
+use	O
+of	O
+transfer	O
+probabilities	O
+and	O
+the	O
+concept	O
+of	O
+likelihood	O
+ratio	O
+.	O
+
+It	O
+is	O
+an	O
+interesting	O
+topic	O
+of	O
+further	O
+research	O
+to	O
+compare	O
+the	O
+two	O
+methods	O
+.	O
+
+So	O
+far	O
+we	O
+only	O
+predicted	O
+the	O
+presence	O
+of	O
+a	O
+key	O
+word	O
+.	O
+
+It	O
+is	O
+quite	O
+a	O
+challenge	O
+to	O
+obtain	O
+a	O
+true	O
+prediction	O
+of	O
+function	O
+.	O
+
+Conclusion	O
+
+The	O
+main	O
+conclusion	O
+of	O
+the	O
+paper	O
+is	O
+that	O
+the	O
+introduction	O
+of	O
+the	O
+concept	O
+of	O
+likelihood	O
+ratio	O
+coming	O
+from	O
+statistical	O
+decision	O
+theory	O
+is	O
+very	O
+helpful	O
+in	O
+the	O
+development	O
+of	O
+automated	O
+annotation	O
+procedures	O
+.	O
+
+We	O
+obtained	O
+a	O
+substantial	O
+improvement	O
+when	O
+compared	O
+with	O
+our	O
+previous	O
+results	O
+.	O
+
+We	O
+are	O
+sure	O
+that	O
+there	O
+is	O
+room	O
+for	O
+further	O
+improvement	O
+.	O
+
+Issues	O
+for	O
+further	O
+research	O
+are	O
+the	O
+size	O
+of	O
+the	O
+set	O
+of	O
+similar	O
+sequences	O
+and	O
+the	O
+combination	O
+of	O
+different	O
+statistics	O
+into	O
+a	O
+"	O
+super	O
+-	O
+predictor	O
+"	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+A	O
+.	O
+M	O
+.	O
+
+Leontovich	O
+and	O
+H	O
+.	O
+C	O
+.	O
+van	O
+Houwelingen	O
+developed	O
+the	O
+approach	O
+.	O
+
+A	O
+.	O
+M	O
+.	O
+
+Leontovich	O
+developed	O
+the	O
+methodology	O
+and	O
+the	O
+algorithms	O
+in	O
+cooperation	O
+with	O
+K	O
+.	O
+Y	O
+.	O
+
+Tokmachev	O
+and	O
+H	O
+.	O
+C	O
+.	O
+van	O
+Houwelingen	O
+.	O
+
+K	O
+.	O
+Y	O
+.	O
+
+Tokmachev	O
+carried	O
+out	O
+all	O
+computations	O
+.	O
+
+Supplementary	O
+Material	O
+
+Borrelia	B
+burgdorferi	I
+membranes	O
+are	O
+the	O
+primary	O
+targets	O
+of	O
+reactive	O
+oxygen	O
+species	O
+
+Abstract	O
+
+Spirochetes	O
+living	O
+in	O
+an	O
+oxygen	O
+-	O
+rich	O
+environment	O
+or	O
+when	O
+challenged	O
+by	O
+host	O
+immune	O
+cells	O
+are	O
+exposed	O
+to	O
+reactive	O
+oxygen	O
+species	O
+(	O
+ROS	O
+)	O
+.	O
+
+These	O
+species	O
+can	O
+harm	O
+/	O
+destroy	O
+cysteinyl	O
+residues	O
+,	O
+iron	O
+-	O
+sulphur	O
+clusters	O
+,	O
+DNA	O
+and	O
+polyunsaturated	O
+lipids	O
+,	O
+leading	O
+to	O
+inhibition	O
+of	O
+growth	O
+or	O
+cell	O
+death	O
+.	O
+
+Because	O
+Borrelia	B
+burgdorferi	I
+contains	O
+no	O
+intracellular	O
+iron	O
+,	O
+DNA	O
+is	O
+most	O
+likely	O
+not	O
+a	O
+major	O
+target	O
+for	O
+ROS	O
+via	O
+Fenton	O
+reaction	O
+.	O
+
+In	O
+support	O
+of	O
+this	O
+,	O
+growth	O
+of	O
+B	B
+.	I
+burgdorferi	I
+in	O
+the	O
+presence	O
+of	O
+5	O
+mM	O
+H2O2	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+DNA	O
+mutation	O
+rate	O
+(	O
+spontaneous	O
+coumermycin	O
+A1	O
+resistance	O
+)	O
+,	O
+and	O
+cells	O
+treated	O
+with	O
+10	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+or	O
+10	O
+mM	O
+H2O2	O
+show	O
+no	O
+increase	O
+in	O
+DNA	O
+damage	O
+.	O
+
+Unlike	O
+most	O
+bacteria	O
+,	O
+B	B
+.	I
+burgdorferi	I
+incorporates	O
+ROS	O
+-	O
+susceptible	O
+polyunsaturated	O
+fatty	O
+acids	O
+from	O
+the	O
+environment	O
+into	O
+their	O
+membranes	O
+.	O
+
+Analysis	O
+of	O
+lipoxidase	O
+-	O
+treated	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+by	O
+Electron	O
+Microscopy	O
+showed	O
+significant	O
+irregularities	O
+indicative	O
+of	O
+membrane	O
+damage	O
+.	O
+
+Fatty	O
+acid	O
+analysis	O
+of	O
+cells	O
+treated	O
+with	O
+lipoxidase	O
+indicated	O
+that	O
+host	O
+-	O
+derived	O
+linoleic	O
+acid	O
+had	O
+been	O
+dramatically	O
+reduced	O
+(	O
+50	O
+-	O
+fold	O
+)	O
+in	O
+these	O
+cells	O
+,	O
+with	O
+a	O
+corresponding	O
+increase	O
+in	O
+the	O
+levels	O
+of	O
+malondialdehyde	O
+by	O
+-	O
+product	O
+(	O
+fourfold	O
+)	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+B	B
+.	I
+burgdorferi	I
+membrane	O
+lipids	O
+are	O
+targets	O
+for	O
+attack	O
+by	O
+ROS	O
+encountered	O
+in	O
+the	O
+various	O
+stages	O
+of	O
+the	O
+infective	O
+cycle	O
+.	O
+
+Introduction	O
+
+Borrelia	B
+burgdorferi	I
+,	O
+the	O
+causative	O
+agent	O
+of	O
+Lyme	O
+disease	O
+,	O
+survives	O
+and	O
+proliferates	O
+in	O
+distinctly	O
+different	O
+niches	O
+,	O
+including	O
+its	O
+arthropod	O
+vector	O
+and	O
+various	O
+mammalian	O
+hosts	O
+.	O
+
+These	O
+'	O
+micro	O
+'	O
+environments	O
+provide	O
+their	O
+own	O
+distinct	O
+sets	O
+of	O
+advantages	O
+and	O
+challenges	O
+to	O
+B	B
+.	I
+burgdorferi	I
+.	O
+
+For	O
+example	O
+,	O
+during	O
+the	O
+initial	O
+stages	O
+of	O
+infection	O
+of	O
+the	O
+mammalian	O
+host	O
+,	O
+immune	O
+cells	O
+attempt	O
+to	O
+prevent	O
+B	B
+.	I
+burgdorferi	I
+from	O
+establishing	O
+an	O
+infection	O
+using	O
+several	O
+systems	O
+including	O
+those	O
+generating	O
+bacteriocidal	O
+reactive	O
+oxygen	O
+species	O
+(	O
+ROS	O
+)	O
+[	O
+e	O
+.	O
+g	O
+.	O
+superoxide	O
+radicals	O
+(	O
+O2	O
+-	O
+)	O
+,	O
+hydrogen	O
+peroxide	O
+(	O
+H2O2	O
+)	O
+and	O
+hydroxyl	O
+radicals	O
+(	O
+OH	O
+)	O
+]	O
+and	O
+reactive	O
+nitrogen	O
+species	O
+(	O
+RNS	O
+)	O
+[	O
+e	O
+.	O
+g	O
+.	O
+nitric	O
+oxide	O
+(	O
+NO	O
+)	O
+and	O
+peroxynitrite	O
+]	O
+(	O
+Storz	O
+and	O
+Imlay	O
+,	O
+1999	O
+)	O
+.	O
+
+In	O
+order	O
+for	O
+B	B
+.	I
+burgdorferi	I
+to	O
+successfully	O
+colonize	O
+a	O
+new	O
+host	O
+and	O
+cause	O
+disease	O
+,	O
+they	O
+must	O
+overcome	O
+the	O
+challenges	O
+posed	O
+by	O
+the	O
+innate	O
+immune	O
+system	O
+including	O
+the	O
+deleterious	O
+effects	O
+of	O
+ROS	O
+/	O
+RNS	O
+compounds	O
+.	O
+
+The	O
+effects	O
+of	O
+ROS	O
+/	O
+RNS	O
+on	O
+cells	O
+have	O
+been	O
+extensively	O
+investigated	O
+.	O
+
+These	O
+highly	O
+reactive	O
+compounds	O
+have	O
+been	O
+shown	O
+to	O
+damage	O
+cellular	O
+macromolecules	O
+including	O
+DNA	O
+,	O
+proteins	O
+and	O
+cellular	O
+membranes	O
+.	O
+
+The	O
+damage	O
+to	O
+membranes	O
+can	O
+arise	O
+through	O
+either	O
+lipid	O
+or	O
+membrane	O
+protein	O
+damage	O
+.	O
+
+In	O
+eukaryotes	O
+,	O
+membrane	O
+lipids	O
+are	O
+a	O
+major	O
+target	O
+of	O
+ROS	O
+.	O
+
+Free	O
+radicals	O
+attack	O
+polyunsaturated	O
+fatty	O
+acids	O
+in	O
+membranes	O
+and	O
+initiate	O
+lipid	O
+peroxidation	O
+.	O
+
+A	O
+primary	O
+effect	O
+of	O
+this	O
+is	O
+a	O
+decrease	O
+in	O
+membrane	O
+fluidity	O
+which	O
+affects	O
+the	O
+physical	O
+properties	O
+of	O
+the	O
+membrane	O
+altering	O
+the	O
+function	O
+of	O
+membrane	O
+-	O
+associated	O
+proteins	O
+.	O
+
+Once	O
+lipid	O
+peroxides	O
+form	O
+,	O
+they	O
+react	O
+with	O
+adjacent	O
+polyunsaturated	O
+lipids	O
+causing	O
+an	O
+amplification	O
+of	O
+the	O
+damage	O
+.	O
+
+Lipid	O
+peroxides	O
+undergo	O
+further	O
+oxidation	O
+to	O
+a	O
+variety	O
+of	O
+products	O
+,	O
+including	O
+aldehydes	O
+,	O
+which	O
+subsequently	O
+react	O
+with	O
+and	O
+damage	O
+membrane	O
+proteins	O
+.	O
+
+However	O
+,	O
+in	O
+bacteria	O
+,	O
+it	O
+is	O
+assumed	O
+that	O
+lipids	O
+are	O
+not	O
+subject	O
+to	O
+the	O
+oxidative	O
+damage	O
+observed	O
+in	O
+eukaryotic	O
+cells	O
+.	O
+
+Only	O
+certain	O
+polyunsaturated	O
+lipids	O
+,	O
+such	O
+as	O
+linoleic	O
+acid	O
+and	O
+linolenic	O
+acid	O
+,	O
+are	O
+susceptible	O
+to	O
+oxidation	O
+(	O
+Gutteridge	O
+and	O
+Halliwell	O
+,	O
+1990	O
+)	O
+,	O
+and	O
+it	O
+is	O
+clear	O
+that	O
+most	O
+bacteria	O
+do	O
+not	O
+synthesize	O
+or	O
+incorporate	O
+these	O
+types	O
+of	O
+lipids	O
+in	O
+their	O
+cell	O
+membrane	O
+.	O
+
+Two	O
+notable	O
+exceptions	O
+are	O
+the	O
+photosynthetic	O
+bacteria	O
+which	O
+synthesize	O
+and	O
+incorporate	O
+significant	O
+levels	O
+of	O
+linoleic	O
+acid	O
+in	O
+their	O
+membrane	O
+(	O
+Tasaka	O
+et	O
+al	O
+.	O
+,	O
+1996	O
+)	O
+and	O
+Helicobacter	B
+pylori	I
+membranes	O
+which	O
+contain	O
+between	O
+0	O
+.	O
+5	O
+%	O
+and	O
+3	O
+%	O
+linoleic	O
+acid	O
+(	O
+Ursini	O
+and	O
+Bindoli	O
+,	O
+1987	O
+)	O
+.	O
+
+Instead	O
+,	O
+it	O
+has	O
+been	O
+shown	O
+that	O
+the	O
+most	O
+damaging	O
+effects	O
+of	O
+ROS	O
+in	O
+bacteria	O
+result	O
+from	O
+the	O
+interactions	O
+of	O
+H2O2	O
+with	O
+'	O
+free	O
+'	O
+Fe2	O
++	O
+(	O
+Imlay	O
+,	O
+2003	O
+)	O
+,	O
+generating	O
+very	O
+reactive	O
+OH	O
+(	O
+Fenton	O
+reaction	O
+)	O
+.	O
+
+Because	O
+of	O
+this	O
+reactivity	O
+,	O
+the	O
+effect	O
+on	O
+any	O
+given	O
+biomolecule	O
+will	O
+depend	O
+largely	O
+upon	O
+proximity	O
+to	O
+the	O
+target	O
+.	O
+
+Because	O
+Fe2	O
++	O
+localizes	O
+along	O
+the	O
+phosphodiester	O
+backbone	O
+of	O
+nucleic	O
+acid	O
+,	O
+DNA	O
+is	O
+a	O
+major	O
+target	O
+of	O
+OH	O
+.	O
+
+This	O
+reactive	O
+species	O
+can	O
+pull	O
+electrons	O
+from	O
+either	O
+the	O
+base	O
+or	O
+sugar	O
+moieties	O
+,	O
+producing	O
+a	O
+variety	O
+of	O
+lesions	O
+including	O
+single	O
+-	O
+and	O
+double	O
+-	O
+stranded	O
+breaks	O
+in	O
+the	O
+backbone	O
+and	O
+chemical	O
+cross	O
+-	O
+links	O
+to	O
+other	O
+molecules	O
+.	O
+
+These	O
+strand	O
+breaks	O
+and	O
+other	O
+lesions	O
+block	O
+DNA	O
+replication	O
+and	O
+contribute	O
+to	O
+OH	O
+toxicity	O
+and	O
+cell	O
+death	O
+.	O
+
+Other	O
+base	O
+damage	O
+,	O
+which	O
+does	O
+not	O
+hinder	O
+replication	O
+,	O
+may	O
+result	O
+in	O
+a	O
+significant	O
+increase	O
+in	O
+mutation	O
+rates	O
+.	O
+
+The	O
+intracellular	O
+biochemistry	O
+of	O
+B	B
+.	I
+burgdorferi	I
+suggests	O
+that	O
+the	O
+primary	O
+cellular	O
+target	O
+of	O
+ROS	O
+may	O
+be	O
+distinct	O
+from	O
+that	O
+described	O
+in	O
+other	O
+bacteria	O
+such	O
+as	O
+Escherichia	B
+coli	I
+.	O
+
+In	O
+E	B
+.	I
+coli	I
+,	O
+the	O
+extent	O
+of	O
+DNA	O
+damage	O
+due	O
+to	O
+H2O2	O
+and	O
+Fenton	O
+chemistry	O
+is	O
+directly	O
+proportional	O
+to	O
+Fe	O
+metabolism	O
+and	O
+the	O
+free	O
+Fe	O
+concentration	O
+within	O
+the	O
+cell	O
+(	O
+10	O
+micro	O
+M	O
+)	O
+(	O
+Keyer	O
+and	O
+Imlay	O
+,	O
+1996	O
+)	O
+.	O
+
+As	O
+the	O
+intracellular	O
+Fe	O
+concentrations	O
+of	O
+B	B
+.	I
+burgdorferi	I
+are	O
+estimated	O
+to	O
+be	O
+<	O
+10	O
+atoms	O
+per	O
+cell	O
+(	O
+Posey	O
+and	O
+Gherardini	O
+,	O
+2000	O
+)	O
+,	O
+it	O
+seems	O
+unlikely	O
+that	O
+DNA	O
+is	O
+a	O
+primary	O
+target	O
+for	O
+ROS	O
+.	O
+
+Therefore	O
+,	O
+the	O
+purpose	O
+of	O
+this	O
+study	O
+is	O
+to	O
+determine	O
+the	O
+biochemical	O
+effects	O
+of	O
+ROS	O
+on	O
+B	B
+.	I
+burgdorferi	I
+,	O
+including	O
+growth	O
+effects	O
+and	O
+biological	O
+/	O
+physical	O
+damage	O
+.	O
+
+Results	O
+
+Effect	O
+of	O
+ROS	O
+on	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+
+In	O
+order	O
+to	O
+determine	O
+what	O
+the	O
+cellular	O
+targets	O
+of	O
+ROS	O
+in	O
+B	B
+.	I
+burgdorferi	I
+are	O
+,	O
+we	O
+first	O
+needed	O
+to	O
+determine	O
+the	O
+sensitivity	O
+of	O
+Borrelia	O
+cells	O
+to	O
+various	O
+oxidants	O
+.	O
+
+Microaerobic	O
+cultures	O
+of	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+were	O
+grown	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+,	O
+treated	O
+with	O
+varying	O
+concentrations	O
+of	O
+H2O2	O
+(	O
+0	O
+-	O
+50	O
+mM	O
+)	O
+or	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+(	O
+0	O
+-	O
+50	O
+mM	O
+)	O
+and	O
+the	O
+number	O
+of	O
+surviving	O
+cells	O
+determined	O
+by	O
+plating	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Fig	O
+.	O
+
+1	O
+.	O
+
+When	O
+cells	O
+were	O
+exposed	O
+to	O
+10	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+,	O
+approximately	O
+50	O
+%	O
+of	O
+the	O
+cells	O
+survive	O
+(	O
+Fig	O
+.	O
+1A	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+when	O
+E	B
+.	I
+coli	I
+cells	O
+were	O
+exposed	O
+to	O
+1	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+,	O
+approximately	O
+1	O
+%	O
+of	O
+the	O
+cells	O
+survive	O
+.	O
+
+B	B
+.	I
+burgdorferi	I
+cells	O
+were	O
+much	O
+more	O
+resistant	O
+to	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+than	O
+E	B
+.	I
+coli	I
+cells	O
+,	O
+with	O
+a	O
+survival	O
+rate	O
+of	O
+approximately	O
+100	O
+%	O
+at	O
+1	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+.	O
+
+This	O
+trend	O
+was	O
+observed	O
+when	O
+cells	O
+were	O
+exposed	O
+to	O
+H2O2	O
+.	O
+
+E	B
+.	I
+coli	I
+cells	O
+exposed	O
+to	O
+1	O
+mM	O
+H2O2	O
+have	O
+approximately	O
+10	O
+%	O
+survivability	O
+,	O
+while	O
+100	O
+%	O
+of	O
+the	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+survive	O
+at	O
+this	O
+concentration	O
+,	O
+and	O
+approximately	O
+80	O
+%	O
+survive	O
+when	O
+exposed	O
+to	O
+10	O
+mM	O
+H2O2	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+Similar	O
+results	O
+were	O
+obtained	O
+when	O
+cells	O
+were	O
+exposed	O
+in	O
+HN	O
+(	O
+Hepes	O
+-	O
+NaCl	O
+)	O
+buffer	O
+,	O
+suggesting	O
+that	O
+the	O
+high	O
+-	O
+level	O
+resistance	O
+to	O
+ROS	O
+was	O
+not	O
+due	O
+to	O
+the	O
+interaction	O
+of	O
+ROS	O
+with	O
+components	O
+of	O
+Barbour	O
+-	O
+Stoenner	O
+-	O
+Kelly	O
+(	O
+BSK	O
+-	O
+II	O
+)	O
+growth	O
+medium	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+indicated	O
+that	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+highly	O
+resistant	O
+to	O
+exposure	O
+to	O
+both	O
+t	O
+-	O
+butyl	O
+peroxide	O
+and	O
+H2O2	O
+.	O
+
+Borrelia	B
+burgdorferi	I
+DNA	O
+is	O
+not	O
+the	O
+primary	O
+target	O
+of	O
+ROS	O
+
+For	O
+most	O
+bacteria	O
+,	O
+DNA	O
+is	O
+the	O
+major	O
+target	O
+of	O
+ROS	O
+causing	O
+a	O
+wide	O
+variety	O
+of	O
+DNA	O
+lesions	O
+.	O
+
+This	O
+is	O
+in	O
+part	O
+due	O
+to	O
+the	O
+localization	O
+of	O
+'	O
+free	O
+'	O
+Fe2	O
++	O
+along	O
+the	O
+phosphodiester	O
+backbone	O
+of	O
+nucleic	O
+acids	O
+,	O
+putting	O
+the	O
+DNA	O
+in	O
+close	O
+proximity	O
+to	O
+the	O
+active	O
+species	O
+formed	O
+via	O
+the	O
+Fenton	O
+reaction	O
+.	O
+
+However	O
+,	O
+B	B
+.	I
+burgdorferi	I
+has	O
+been	O
+shown	O
+to	O
+harbour	O
+few	O
+genes	O
+encoding	O
+orthologues	O
+of	O
+known	O
+iron	O
+-	O
+containing	O
+proteins	O
+,	O
+does	O
+not	O
+require	O
+Fe	O
+for	O
+growth	O
+and	O
+has	O
+intracellular	O
+Fe	O
+concentrations	O
+estimated	O
+to	O
+be	O
+<	O
+10	O
+atoms	O
+per	O
+cell	O
+(	O
+Posey	O
+and	O
+Gherardini	O
+,	O
+2000	O
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+observations	O
+strongly	O
+suggest	O
+that	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+is	O
+not	O
+a	O
+major	O
+target	O
+for	O
+ROS	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+different	O
+techniques	O
+were	O
+used	O
+to	O
+measure	O
+DNA	O
+damage	O
+in	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+after	O
+exposure	O
+to	O
+ROS	O
+.	O
+
+One	O
+reliable	O
+indicator	O
+of	O
+DNA	O
+damage	O
+by	O
+ROS	O
+in	O
+a	O
+cell	O
+is	O
+an	O
+increase	O
+in	O
+the	O
+spontaneous	O
+mutation	O
+rate	O
+.	O
+
+In	O
+B	B
+.	I
+burgdorferi	I
+,	O
+mutations	O
+that	O
+confer	O
+resistance	O
+to	O
+coumermycin	O
+A1	O
+,	O
+which	O
+targets	O
+the	O
+beta	O
+subunit	O
+of	O
+DNA	O
+gyrase	O
+,	O
+have	O
+been	O
+mapped	O
+to	O
+gyrB	O
+,	O
+the	O
+gene	O
+encoding	O
+DNA	O
+gyrase	O
+B	O
+(	O
+Samuels	O
+et	O
+al	O
+.	O
+,	O
+1994	O
+)	O
+.	O
+
+In	O
+each	O
+case	O
+,	O
+a	O
+single	O
+point	O
+mutation	O
+correlated	O
+with	O
+this	O
+drug	O
+resistance	O
+.	O
+
+To	O
+determine	O
+if	O
+exposure	O
+to	O
+oxidants	O
+increases	O
+DNA	O
+damage	O
+by	O
+increasing	O
+point	O
+mutations	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+were	O
+treated	O
+with	O
+5	O
+mM	O
+H2O2	O
+and	O
+plated	O
+in	O
+the	O
+presence	O
+and	O
+absence	O
+of	O
+250	O
+ng	O
+ml	O
+-	O
+1	O
+coumermycin	O
+A1	O
+.	O
+
+The	O
+mutation	O
+frequency	O
+was	O
+calculated	O
+as	O
+the	O
+number	O
+of	O
+colonies	O
+that	O
+are	O
+CouR	O
+per	O
+total	O
+number	O
+of	O
+cells	O
+plated	O
+.	O
+
+The	O
+spontaneous	O
+resistance	O
+frequency	O
+of	O
+treated	O
+cells	O
+was	O
+approximately	O
+equivalent	O
+to	O
+that	O
+of	O
+untreated	O
+cells	O
+,	O
+8	O
+.	O
+8	O
+x	O
+10	O
+-	O
+8	O
+and	O
+1	O
+.	O
+33	O
+x	O
+10	O
+-	O
+7	O
+,	O
+respectively	O
+,	O
+indicating	O
+no	O
+increase	O
+in	O
+the	O
+number	O
+of	O
+point	O
+mutations	O
+(	O
+Fig	O
+.	O
+2A	O
+)	O
+.	O
+
+Also	O
+,	O
+no	O
+increase	O
+in	O
+point	O
+mutations	O
+was	O
+observed	O
+when	O
+cells	O
+were	O
+treated	O
+with	O
+higher	O
+concentrations	O
+of	O
+H2O2	O
+(	O
+10	O
+mM	O
+)	O
+or	O
+when	O
+treated	O
+with	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+(	O
+5	O
+and	O
+10	O
+mM	O
+)	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Another	O
+effective	O
+way	O
+to	O
+determine	O
+DNA	O
+damage	O
+is	O
+by	O
+measuring	O
+the	O
+number	O
+of	O
+apurinic	O
+/	O
+apyrimidinic	O
+sites	O
+(	O
+AP	O
+)	O
+.	O
+
+AP	O
+sites	O
+in	O
+DNA	O
+,	O
+where	O
+the	O
+DNA	O
+base	O
+is	O
+lost	O
+,	O
+can	O
+be	O
+generated	O
+spontaneously	O
+under	O
+physiological	O
+conditions	O
+by	O
+hydrolysis	O
+of	O
+the	O
+N	O
+-	O
+glycosylic	O
+bond	O
+,	O
+or	O
+can	O
+also	O
+be	O
+formed	O
+by	O
+DNA	O
+-	O
+damaging	O
+agents	O
+(	O
+Lindahl	O
+and	O
+Nyberg	O
+,	O
+1972	O
+)	O
+,	O
+such	O
+as	O
+UV	O
+,	O
+alkylating	O
+agents	O
+or	O
+OH	O
+.	O
+
+They	O
+are	O
+also	O
+intermediates	O
+in	O
+the	O
+base	O
+excision	O
+repair	O
+pathway	O
+(	O
+BER	O
+)	O
+(	O
+Weiss	O
+and	O
+Grossman	O
+,	O
+1987	O
+;	O
+Friedberg	O
+and	O
+Hanawalt	O
+,	O
+1988	O
+;	O
+Wallace	O
+,	O
+1988	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+cellular	O
+steady	O
+state	O
+level	O
+of	O
+AP	O
+sites	O
+would	O
+increase	O
+as	O
+a	O
+consequence	O
+of	O
+base	O
+modifications	O
+and	O
+their	O
+subsequent	O
+repair	O
+.	O
+
+As	O
+AP	O
+sites	O
+are	O
+bypassed	O
+inefficiently	O
+by	O
+DNA	O
+polymerase	O
+in	O
+bacterial	O
+cells	O
+,	O
+DNA	O
+lesions	O
+can	O
+result	O
+in	O
+a	O
+significant	O
+block	O
+in	O
+DNA	O
+replication	O
+.	O
+
+Therefore	O
+,	O
+the	O
+number	O
+of	O
+AP	O
+sites	O
+can	O
+serve	O
+as	O
+a	O
+sensitive	O
+indicator	O
+of	O
+DNA	O
+damage	O
+resulting	O
+from	O
+oxidative	O
+stress	O
+(	O
+Kubo	O
+et	O
+al	O
+.	O
+,	O
+1992	O
+)	O
+.	O
+
+To	O
+determine	O
+whether	O
+ROS	O
+can	O
+damage	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+,	O
+strain	O
+B31A3	O
+cells	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+were	O
+treated	O
+with	O
+H2O2	O
+(	O
+1	O
+or	O
+10	O
+mM	O
+)	O
+,	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+(	O
+1	O
+or	O
+10	O
+mM	O
+)	O
+or	O
+lipoxidase	O
+(	O
+an	O
+enzyme	O
+which	O
+specifically	O
+catalyses	O
+the	O
+hydroperoxidation	O
+of	O
+lipids	O
+containing	O
+a	O
+cis	O
+,	O
+cis	O
+-	O
+pentadiene	O
+structure	O
+,	O
+such	O
+as	O
+linoleic	O
+acid	O
+)	O
+.	O
+
+The	O
+DNA	O
+was	O
+isolated	O
+and	O
+assayed	O
+for	O
+AP	O
+sites	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Fig	O
+.	O
+
+2B	O
+.	O
+
+In	O
+all	O
+cases	O
+,	O
+the	O
+numbers	O
+of	O
+AP	O
+sites	O
+per	O
+105	O
+bp	O
+DNA	O
+were	O
+equivalent	O
+,	O
+indicating	O
+that	O
+the	O
+addition	O
+of	O
+oxidants	O
+did	O
+not	O
+increase	O
+the	O
+number	O
+of	O
+DNA	O
+base	O
+lesions	O
+.	O
+
+In	O
+contrast	O
+,	O
+when	O
+E	B
+.	I
+coli	I
+strain	O
+TA4315	O
+cells	O
+(	O
+ahpCF	O
+)	O
+(	O
+Storz	O
+et	O
+al	O
+.	O
+,	O
+1989	O
+)	O
+were	O
+treated	O
+with	O
+100	O
+micro	O
+M	O
+H2O2	O
+,	O
+the	O
+number	O
+of	O
+AP	O
+sites	O
+increased	O
+~	O
+10	O
+-	O
+fold	O
+over	O
+untreated	O
+cells	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+was	O
+not	O
+a	O
+major	O
+target	O
+for	O
+oxidative	O
+damage	O
+under	O
+these	O
+conditions	O
+.	O
+
+It	O
+is	O
+of	O
+note	O
+to	O
+mention	O
+that	O
+the	O
+total	O
+number	O
+of	O
+AP	O
+sites	O
+per	O
+105	O
+bp	O
+DNA	O
+is	O
+approximately	O
+10	O
+-	O
+fold	O
+higher	O
+in	O
+untreated	O
+Borrelia	O
+B31A3	O
+DNA	O
+than	O
+in	O
+untreated	O
+E	B
+.	I
+coli	I
+DNA	O
+.	O
+
+The	O
+Borrelia	O
+genome	O
+consists	O
+of	O
+a	O
+linear	O
+chromosome	O
+and	O
+multiple	O
+linear	O
+and	O
+circular	O
+plasmids	O
+.	O
+
+Numerous	O
+observations	O
+indicate	O
+that	O
+functional	O
+telomeres	O
+require	O
+interaction	O
+with	O
+DNA	O
+damage	O
+repair	O
+proteins	O
+,	O
+suggesting	O
+that	O
+the	O
+DNA	O
+damage	O
+repair	O
+machinery	O
+,	O
+including	O
+the	O
+BER	O
+,	O
+is	O
+involved	O
+in	O
+replication	O
+of	O
+telomeres	O
+and	O
+protection	O
+of	O
+functional	O
+chromosome	O
+ends	O
+(	O
+Verdun	O
+and	O
+Karlseder	O
+,	O
+2007	O
+)	O
+.	O
+
+An	O
+important	O
+intermediate	O
+in	O
+BER	O
+is	O
+the	O
+apurinic	O
+or	O
+abasic	O
+site	O
+.	O
+
+Therefore	O
+,	O
+it	O
+was	O
+possible	O
+that	O
+the	O
+higher	O
+numbers	O
+of	O
+AP	O
+sites	O
+in	O
+untreated	O
+Borrelia	O
+DNA	O
+was	O
+due	O
+to	O
+the	O
+number	O
+of	O
+telomeres	O
+present	O
+in	O
+the	O
+genome	O
+.	O
+
+The	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+harbours	O
+11	O
+linear	O
+plasmids	O
+and	O
+a	O
+linear	O
+chromosome	O
+with	O
+~	O
+100	O
+unpaired	O
+bases	O
+in	O
+the	O
+telomere	O
+loops	O
+per	O
+genome	O
+or	O
+10	O
+bases	O
+per	O
+105	O
+bp	O
+DNA	O
+(	O
+Hinnebusch	O
+and	O
+Barbour	O
+,	O
+1991	O
+;	O
+Chaconas	O
+,	O
+2005	O
+)	O
+.	O
+
+Untreated	O
+Borrelia	O
+B31A3	O
+contains	O
+11	O
++	O
+/	O
+-	O
+3	O
+.	O
+8	O
+AP	O
+sites	O
+per	O
+105	O
+bp	O
+DNA	O
+,	O
+suggesting	O
+that	O
+the	O
+elevated	O
+number	O
+of	O
+AP	O
+sites	O
+in	O
+Borrelia	O
+was	O
+due	O
+to	O
+the	O
+number	O
+of	O
+telomeres	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+the	O
+AP	O
+sites	O
+were	O
+measured	O
+in	O
+DNA	O
+isolated	O
+from	O
+untreated	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B314	O
+which	O
+harbours	O
+no	O
+linear	O
+plasmids	O
+(	O
+Sadziene	O
+et	O
+al	O
+.	O
+,	O
+1993	O
+)	O
+.	O
+
+The	O
+number	O
+of	O
+unpaired	O
+bases	O
+in	O
+the	O
+telomere	O
+loops	O
+per	O
+genome	O
+was	O
+estimated	O
+to	O
+be	O
+10	O
+,	O
+which	O
+corresponds	O
+to	O
+1	O
+base	O
+per	O
+105	O
+bp	O
+DNA	O
+,	O
+and	O
+only	O
+3	O
+.	O
+6	O
++	O
+/	O
+-	O
+0	O
+.	O
+2	O
+AP	O
+sites	O
+per	O
+105	O
+bp	O
+DNA	O
+were	O
+detected	O
+,	O
+supporting	O
+the	O
+hypothesis	O
+that	O
+the	O
+high	O
+number	O
+of	O
+AP	O
+sites	O
+in	O
+untreated	O
+Borrelia	O
+DNA	O
+was	O
+due	O
+to	O
+the	O
+number	O
+of	O
+unpaired	O
+bases	O
+in	O
+the	O
+telomeres	O
+.	O
+
+The	O
+analyses	O
+of	O
+the	O
+AP	O
+sites	O
+strongly	O
+suggested	O
+that	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+was	O
+not	O
+the	O
+major	O
+target	O
+for	O
+oxidative	O
+damage	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+generation	O
+of	O
+abasic	O
+sites	O
+,	O
+oxygen	O
+radicals	O
+often	O
+damage	O
+DNA	O
+through	O
+the	O
+formation	O
+of	O
+8	O
+-	O
+oxoguanine	O
+lesions	O
+(	O
+Nakamura	O
+et	O
+al	O
+.	O
+,	O
+2000	O
+)	O
+.	O
+
+8	O
+-	O
+Oxoguanine	O
+,	O
+through	O
+its	O
+ability	O
+to	O
+mispair	O
+with	O
+bases	O
+other	O
+than	O
+cytosine	O
+,	O
+likely	O
+plays	O
+a	O
+role	O
+in	O
+DNA	O
+mutagenesis	O
+.	O
+
+Consequently	O
+,	O
+8	O
+-	O
+oxoguanine	O
+is	O
+often	O
+used	O
+as	O
+a	O
+marker	O
+of	O
+oxidized	O
+DNA	O
+damage	O
+.	O
+
+To	O
+determine	O
+whether	O
+ROS	O
+can	O
+damage	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+and	O
+cause	O
+8	O
+-	O
+oxoguanine	O
+lesions	O
+,	O
+strain	O
+B31A3	O
+cells	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+were	O
+treated	O
+with	O
+H2O2	O
+(	O
+5	O
+or	O
+10	O
+mM	O
+)	O
+,	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+(	O
+5	O
+or	O
+10	O
+mM	O
+)	O
+or	O
+lipoxidase	O
+.	O
+
+The	O
+DNA	O
+was	O
+isolated	O
+and	O
+assayed	O
+for	O
+8	O
+-	O
+oxoguanine	O
+using	O
+an	O
+Enzyme	O
+-	O
+Linked	O
+ImmunoSorbent	O
+Assay	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Fig	O
+.	O
+
+2C	O
+.	O
+
+In	O
+all	O
+cases	O
+,	O
+the	O
+amount	O
+of	O
+8	O
+-	O
+oxoguanine	O
+in	O
+Borrelia	O
+cells	O
+was	O
+below	O
+the	O
+detection	O
+limit	O
+of	O
+the	O
+assay	O
+.	O
+
+In	O
+contrast	O
+,	O
+when	O
+a	O
+MutM	O
+(	O
+the	O
+specific	O
+glycosylase	O
+that	O
+removes	O
+the	O
+8	O
+-	O
+oxoguanine	O
+)	O
+-	O
+deficient	O
+E	B
+.	I
+coli	I
+strain	O
+was	O
+treated	O
+with	O
+100	O
+micro	O
+M	O
+H2O2	O
+,	O
+the	O
+amount	O
+of	O
+8	O
+-	O
+oxoguanine	O
+sites	O
+increased	O
+~	O
+fivefold	O
+over	O
+untreated	O
+cells	O
+.	O
+
+It	O
+is	O
+important	O
+to	O
+point	O
+out	O
+that	O
+no	O
+MutM	O
+homologue	O
+has	O
+been	O
+identified	O
+in	O
+the	O
+genome	O
+of	O
+B	B
+.	I
+burgdorferi	I
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+suggested	O
+that	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+was	O
+not	O
+a	O
+major	O
+target	O
+for	O
+oxidative	O
+damage	O
+under	O
+these	O
+conditions	O
+.	O
+
+The	O
+membranes	O
+of	O
+B	B
+.	I
+burgdorferi	I
+are	O
+targeted	O
+during	O
+oxidative	O
+stress	O
+
+In	O
+eukaryotes	O
+,	O
+membrane	O
+lipids	O
+are	O
+a	O
+major	O
+target	O
+of	O
+ROS	O
+.	O
+
+Free	O
+radicals	O
+can	O
+attack	O
+polyunsaturated	O
+fatty	O
+acids	O
+,	O
+such	O
+as	O
+linoleic	O
+acid	O
+and	O
+linolenic	O
+acid	O
+,	O
+in	O
+membranes	O
+and	O
+initiate	O
+lipid	O
+peroxidation	O
+.	O
+
+This	O
+reaction	O
+can	O
+cascade	O
+throughout	O
+the	O
+membrane	O
+to	O
+adjacent	O
+polyunsaturated	O
+fatty	O
+acids	O
+,	O
+decreasing	O
+membrane	O
+fluidity	O
+and	O
+generating	O
+more	O
+toxic	O
+products	O
+such	O
+as	O
+aldehydes	O
+(	O
+Imlay	O
+,	O
+2003	O
+)	O
+.	O
+
+Because	O
+most	O
+bacterial	O
+membranes	O
+contain	O
+saturated	O
+and	O
+monounsaturated	O
+fatty	O
+acids	O
+rather	O
+than	O
+'	O
+reactive	O
+'	O
+polyunsaturated	O
+lipids	O
+,	O
+peroxidation	O
+of	O
+lipids	O
+in	O
+bacterial	O
+membranes	O
+is	O
+not	O
+considered	O
+a	O
+problem	O
+.	O
+
+As	O
+B	B
+.	I
+burgdorferi	I
+cannot	O
+synthesize	O
+their	O
+own	O
+lipids	O
+,	O
+they	O
+must	O
+instead	O
+scavenge	O
+them	O
+.	O
+
+Therefore	O
+,	O
+it	O
+seems	O
+likely	O
+that	O
+their	O
+membrane	O
+composition	O
+would	O
+reflect	O
+the	O
+host	O
+'	O
+s	O
+lipid	O
+profile	O
+or	O
+that	O
+of	O
+their	O
+growth	O
+medium	O
+(	O
+Barbour	O
+,	O
+1984	O
+;	O
+Fraser	O
+et	O
+al	O
+.	O
+,	O
+1997	O
+)	O
+and	O
+would	O
+contain	O
+some	O
+polyunsaturated	O
+fatty	O
+acids	O
+.	O
+
+To	O
+determine	O
+if	O
+B	B
+.	I
+burgdorferi	I
+contains	O
+polyunsaturated	O
+lipids	O
+,	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+grown	O
+under	O
+anaerobic	O
+conditions	O
+and	O
+analysed	O
+for	O
+fatty	O
+acid	O
+composition	O
+by	O
+Lipid	O
+Technologies	O
+(	O
+Austin	O
+,	O
+MN	O
+)	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Table	O
+1	O
+and	O
+are	O
+reported	O
+as	O
+percentage	O
+of	O
+total	O
+fatty	O
+acid	O
+content	O
+.	O
+
+Linoleic	O
+acid	O
+comprised	O
+~	O
+10	O
+%	O
+of	O
+the	O
+total	O
+lipid	O
+content	O
+and	O
+the	O
+linolenic	O
+acid	O
+content	O
+was	O
+measured	O
+to	O
+be	O
+~	O
+1	O
+%	O
+,	O
+indicating	O
+that	O
+Borrelia	O
+cells	O
+do	O
+contain	O
+lipids	O
+that	O
+are	O
+susceptible	O
+to	O
+ROS	O
+damage	O
+.	O
+
+The	O
+amount	O
+of	O
+linoleic	O
+acid	O
+and	O
+linolenic	O
+acid	O
+present	O
+in	O
+Borrelia	O
+reflected	O
+the	O
+amount	O
+present	O
+in	O
+the	O
+media	O
+.	O
+
+Therefore	O
+,	O
+these	O
+results	O
+suggested	O
+that	O
+the	O
+amount	O
+of	O
+these	O
+fatty	O
+acids	O
+in	O
+the	O
+membranes	O
+would	O
+vary	O
+as	O
+availability	O
+varies	O
+.	O
+
+To	O
+determine	O
+if	O
+Borrelia	O
+polyunsaturated	O
+lipids	O
+can	O
+undergo	O
+lipid	O
+peroxidation	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+grown	O
+microaerobically	O
+were	O
+treated	O
+with	O
+1	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+or	O
+250	O
+mg	O
+of	O
+lipoxidase	O
+,	O
+and	O
+the	O
+cell	O
+pellets	O
+were	O
+analysed	O
+for	O
+fatty	O
+acid	O
+composition	O
+(	O
+Industrial	O
+Laboratory	O
+)	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Table	O
+2	O
+and	O
+are	O
+reported	O
+as	O
+the	O
+percentage	O
+of	O
+total	O
+cell	O
+mass	O
+.	O
+
+The	O
+per	O
+cent	O
+of	O
+linoleic	O
+acid	O
+in	O
+the	O
+total	O
+cell	O
+mass	O
+decreased	O
+with	O
+treatment	O
+,	O
+while	O
+the	O
+levels	O
+of	O
+oleic	O
+acid	O
+(	O
+c18	O
+:	O
+1n9	O
+)	O
+and	O
+pentadecanoic	O
+acid	O
+(	O
+c15	O
+:	O
+0	O
+)	O
+remained	O
+relatively	O
+constant	O
+.	O
+
+Untreated	O
+cells	O
+contained	O
+0	O
+.	O
+04	O
+%	O
+linoleic	O
+acid	O
+,	O
+while	O
+cells	O
+treated	O
+with	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+contained	O
+10	O
+-	O
+fold	O
+less	O
+(	O
+0	O
+.	O
+004	O
+%	O
+)	O
+linoleic	O
+acid	O
+and	O
+cells	O
+treated	O
+with	O
+lipoxidase	O
+had	O
+no	O
+detectable	O
+linoleic	O
+acid	O
+present	O
+in	O
+the	O
+sample	O
+.	O
+
+These	O
+data	O
+indicated	O
+that	O
+the	O
+linoleic	O
+acid	O
+present	O
+in	O
+B	B
+.	I
+burgdorferi	I
+membranes	O
+can	O
+be	O
+oxidized	O
+by	O
+ROS	O
+.	O
+
+Malondialdehyde	O
+(	O
+MDA	O
+)	O
+is	O
+generated	O
+as	O
+a	O
+relatively	O
+stable	O
+end	O
+-	O
+product	O
+from	O
+the	O
+oxidative	O
+degradation	O
+of	O
+polyunsaturated	O
+fatty	O
+acids	O
+.	O
+
+MDA	O
+has	O
+thus	O
+been	O
+used	O
+as	O
+an	O
+indicator	O
+of	O
+lipid	O
+peroxidation	O
+(	O
+Gutteridge	O
+and	O
+Halliwell	O
+,	O
+1990	O
+;	O
+Esterbauer	O
+et	O
+al	O
+.	O
+,	O
+1991	O
+)	O
+.	O
+
+To	O
+further	O
+demonstrate	O
+that	O
+Borrelia	O
+lipids	O
+can	O
+undergo	O
+lipid	O
+peroxidation	O
+,	O
+B31A3	O
+cells	O
+grown	O
+microaerobically	O
+were	O
+treated	O
+with	O
+5	O
+mM	O
+AAPH	O
+(	O
+free	O
+radical	O
+generator	O
+)	O
+or	O
+250	O
+mg	O
+of	O
+lipoxidase	O
+and	O
+MDA	O
+measured	O
+(	O
+Seljeskog	O
+et	O
+al	O
+.	O
+,	O
+2006	O
+)	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Fig	O
+.	O
+
+3	O
+.	O
+
+Untreated	O
+cells	O
+contained	O
+~	O
+16	O
+.	O
+5	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+.	O
+
+When	O
+the	O
+cells	O
+were	O
+treated	O
+with	O
+AAPH	O
+or	O
+lipoxidase	O
+,	O
+the	O
+amount	O
+of	O
+MDA	O
+increased	O
+~	O
+1	O
+.	O
+5	O
+-	O
+fold	O
+(	O
+27	O
+.	O
+3	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+and	O
+approximately	O
+twofold	O
+(	O
+33	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+respectively	O
+(	O
+Fig	O
+.	O
+3A	O
+)	O
+.	O
+
+As	O
+a	O
+control	O
+,	O
+eukaryotic	O
+cells	O
+(	O
+mouse	B
+myeloma	O
+cells	O
+SP2	O
+)	O
+were	O
+treated	O
+with	O
+AAPH	O
+and	O
+MDA	O
+measured	O
+(	O
+Fig	O
+.	O
+3B	O
+)	O
+.	O
+
+Mouse	B
+myeloma	O
+cells	O
+have	O
+been	O
+used	O
+as	O
+a	O
+model	O
+system	O
+for	O
+the	O
+determination	O
+of	O
+phospholipid	O
+hydroperoxides	O
+(	O
+Chotimarkorn	O
+et	O
+al	O
+.	O
+,	O
+2005	O
+)	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+the	O
+amount	O
+of	O
+MDA	O
+increased	O
+approximately	O
+threefold	O
+(	O
+36	O
+.	O
+3	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+in	O
+the	O
+treated	O
+cells	O
+versus	O
+untreated	O
+cells	O
+(	O
+11	O
+.	O
+7	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+suggested	O
+that	O
+,	O
+like	O
+eukaryotic	O
+membranes	O
+,	O
+Borrelia	O
+membrane	O
+lipids	O
+were	O
+capable	O
+of	O
+undergoing	O
+lipid	O
+peroxidation	O
+.	O
+
+As	O
+shown	O
+in	O
+Fig	O
+.	O
+
+3A	O
+,	O
+there	O
+is	O
+a	O
+measurable	O
+quantity	O
+of	O
+MDA	O
+present	O
+even	O
+in	O
+untreated	O
+cells	O
+,	O
+suggesting	O
+that	O
+the	O
+membrane	O
+lipids	O
+are	O
+damaged	O
+without	O
+the	O
+addition	O
+of	O
+exogenous	O
+ROS	O
+.	O
+
+Oxidative	O
+damage	O
+is	O
+an	O
+unavoidable	O
+by	O
+-	O
+product	O
+of	O
+growth	O
+in	O
+an	O
+oxygen	O
+environment	O
+because	O
+superoxide	O
+anions	O
+and	O
+H2O2	O
+are	O
+formed	O
+whenever	O
+molecular	O
+oxygen	O
+chemically	O
+oxidizes	O
+electron	O
+carriers	O
+.	O
+
+To	O
+determine	O
+if	O
+the	O
+Borrelia	O
+lipids	O
+are	O
+damaged	O
+from	O
+growth	O
+in	O
+an	O
+oxygen	O
+environment	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+were	O
+grown	O
+under	O
+anaerobic	O
+,	O
+microaerobic	O
+and	O
+aerobic	O
+conditions	O
+and	O
+MDA	O
+measured	O
+.	O
+
+Figure	O
+3C	O
+demonstrates	O
+that	O
+as	O
+the	O
+oxygen	O
+concentration	O
+increased	O
+,	O
+the	O
+amount	O
+of	O
+MDA	O
+increased	O
+.	O
+
+Cells	O
+grown	O
+under	O
+anaerobic	O
+conditions	O
+contained	O
+the	O
+lowest	O
+amount	O
+of	O
+MDA	O
+(	O
+7	O
+.	O
+6	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+,	O
+approximately	O
+twofold	O
+less	O
+than	O
+the	O
+measured	O
+amount	O
+in	O
+microaerobic	O
+cells	O
+(	O
+16	O
+.	O
+5	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+.	O
+
+Aerobically	O
+grown	O
+cells	O
+contained	O
+the	O
+highest	O
+amount	O
+of	O
+MDA	O
+,	O
+~	O
+1	O
+.	O
+5	O
+-	O
+fold	O
+greater	O
+than	O
+that	O
+observed	O
+in	O
+microaerobic	O
+cells	O
+(	O
+28	O
+.	O
+8	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+)	O
+and	O
+~	O
+3	O
+.	O
+7	O
+-	O
+fold	O
+greater	O
+than	O
+that	O
+observed	O
+in	O
+anaerobically	O
+grown	O
+cells	O
+.	O
+
+These	O
+data	O
+suggested	O
+that	O
+Borrelia	O
+lipids	O
+can	O
+be	O
+damaged	O
+during	O
+aerobic	O
+growth	O
+.	O
+
+Our	O
+High	O
+Performance	O
+Liquid	O
+Chromatography	O
+analyses	O
+of	O
+the	O
+MDA	O
+present	O
+in	O
+anaerobically	O
+grown	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+showed	O
+a	O
+small	O
+peak	O
+with	O
+a	O
+retention	O
+time	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+MDA	O
+standard	O
+.	O
+
+This	O
+was	O
+puzzling	O
+as	O
+little	O
+or	O
+no	O
+lipid	O
+peroxidation	O
+should	O
+occur	O
+under	O
+these	O
+conditions	O
+.	O
+
+To	O
+further	O
+characterize	O
+this	O
+'	O
+MDA	O
+'	O
+peak	O
+,	O
+a	O
+three	O
+-	O
+dimensional	O
+diode	O
+array	O
+spectra	O
+was	O
+generated	O
+by	O
+scanning	O
+each	O
+sample	O
+during	O
+the	O
+elution	O
+of	O
+the	O
+peak	O
+(	O
+Fig	O
+.	O
+4	O
+,	O
+lower	O
+sections	O
+)	O
+.	O
+
+An	O
+authentic	O
+MDA	O
+standard	O
+was	O
+also	O
+scanned	O
+as	O
+a	O
+control	O
+(	O
+Fig	O
+.	O
+4A	O
+,	O
+lower	O
+section	O
+)	O
+.	O
+
+In	O
+the	O
+anaerobically	O
+grown	O
+cells	O
+,	O
+the	O
+spectrum	O
+shows	O
+that	O
+two	O
+compounds	O
+with	O
+different	O
+absorbance	O
+maximums	O
+(	O
+Fig	O
+.	O
+4B	O
+,	O
+lower	O
+section	O
+)	O
+comprised	O
+the	O
+single	O
+retention	O
+time	O
+peak	O
+from	O
+the	O
+HPLC	O
+chromatogram	O
+(	O
+Fig	O
+.	O
+4B	O
+,	O
+upper	O
+section	O
+)	O
+.	O
+
+Based	O
+on	O
+this	O
+spectrum	O
+,	O
+the	O
+amount	O
+of	O
+actual	O
+MDA	O
+contributed	O
+<	O
+15	O
+%	O
+of	O
+the	O
+total	O
+amount	O
+of	O
+material	O
+detected	O
+in	O
+the	O
+HPLC	O
+peak	O
+while	O
+the	O
+second	O
+contaminating	O
+peak	O
+contributed	O
+>	O
+85	O
+%	O
+.	O
+
+Therefore	O
+,	O
+the	O
+amount	O
+of	O
+MDA	O
+in	O
+untreated	O
+anaerobically	O
+grown	O
+cells	O
+was	O
+considerably	O
+less	O
+than	O
+the	O
+7	O
+.	O
+6	O
+micro	O
+M	O
+of	O
+MDA	O
+per	O
+mg	O
+of	O
+protein	O
+actually	O
+measured	O
+.	O
+
+However	O
+,	O
+in	O
+cells	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+,	O
+the	O
+MDA	O
+peak	O
+contributed	O
+more	O
+to	O
+the	O
+overall	O
+retention	O
+time	O
+peak	O
+when	O
+compared	O
+with	O
+the	O
+anaerobic	O
+spectrum	O
+,	O
+while	O
+the	O
+second	O
+contaminating	O
+peak	O
+stays	O
+relatively	O
+constant	O
+(	O
+Fig	O
+.	O
+4C	O
+,	O
+lower	O
+section	O
+)	O
+.	O
+
+These	O
+spectra	O
+demonstrated	O
+that	O
+the	O
+increase	O
+in	O
+the	O
+MDA	O
+retention	O
+time	O
+peak	O
+between	O
+anaerobically	O
+and	O
+aerobically	O
+grown	O
+cells	O
+was	O
+due	O
+to	O
+the	O
+increase	O
+in	O
+the	O
+amount	O
+of	O
+authentic	O
+MDA	O
+present	O
+.	O
+
+The	O
+fluorescent	O
+probe	O
+diphenyl	O
+-	O
+1	O
+-	O
+pyrenylphophine	O
+(	O
+DPPP	O
+)	O
+has	O
+been	O
+used	O
+for	O
+detection	O
+of	O
+lipid	O
+hydroperoxides	O
+in	O
+cell	O
+membranes	O
+(	O
+Okimoto	O
+et	O
+al	O
+.	O
+,	O
+2000	O
+;	O
+Takahashi	O
+et	O
+al	O
+.	O
+,	O
+2001	O
+)	O
+.	O
+
+In	O
+this	O
+method	O
+,	O
+the	O
+hydroperoxides	O
+are	O
+reduced	O
+with	O
+DPPP	O
+,	O
+resulting	O
+in	O
+the	O
+formation	O
+of	O
+the	O
+fluorescent	O
+arylphosphine	O
+oxide	O
+.	O
+
+To	O
+visualize	O
+the	O
+lipid	O
+hydroperoxides	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+were	O
+labelled	O
+with	O
+DPPP	O
+and	O
+observed	O
+by	O
+fluorescence	O
+microscopy	O
+(	O
+Fig	O
+.	O
+5B	O
+)	O
+.	O
+
+E	B
+.	I
+coli	I
+Top10	O
+cells	O
+and	O
+mouse	B
+myeloma	O
+SP2	O
+cells	O
+were	O
+also	O
+labelled	O
+and	O
+visualized	O
+to	O
+serve	O
+as	O
+negative	O
+and	O
+positive	O
+controls	O
+respectively	O
+(	O
+Fig	O
+.	O
+5A	O
+and	O
+C	O
+)	O
+.	O
+
+Red	O
+Fluorescent	O
+dye	O
+was	O
+used	O
+to	O
+visualize	O
+the	O
+cell	O
+membranes	O
+.	O
+
+A	O
+strong	O
+fluorescence	O
+of	O
+DPPP	O
+was	O
+observed	O
+for	O
+B31A3	O
+cells	O
+(	O
+Fig	O
+.	O
+5B	O
+)	O
+and	O
+for	O
+the	O
+mouse	B
+myeloma	O
+cells	O
+(	O
+Fig	O
+.	O
+5C	O
+)	O
+,	O
+but	O
+not	O
+for	O
+the	O
+E	B
+.	I
+coli	I
+cells	O
+(	O
+Fig	O
+.	O
+5A	O
+)	O
+.	O
+
+An	O
+overlay	O
+of	O
+the	O
+two	O
+dyes	O
+demonstrates	O
+that	O
+the	O
+DPPP	O
+fluorescence	O
+of	O
+both	O
+the	O
+Borrelia	O
+and	O
+myeloma	O
+cells	O
+corresponds	O
+to	O
+the	O
+areas	O
+of	O
+red	O
+fluorescence	O
+.	O
+
+This	O
+indicated	O
+that	O
+lipid	O
+hydroperoxides	O
+were	O
+present	O
+on	O
+the	O
+Borrelia	O
+cell	O
+membranes	O
+and	O
+suggested	O
+that	O
+the	O
+membranes	O
+were	O
+damaged	O
+.	O
+
+To	O
+further	O
+demonstrate	O
+Borrelia	O
+membrane	O
+damage	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+were	O
+grown	O
+under	O
+anaerobic	O
+and	O
+microaerobic	O
+conditions	O
+and	O
+visualized	O
+by	O
+negative	O
+stain	O
+using	O
+an	O
+electron	O
+microscope	O
+.	O
+
+Additionally	O
+,	O
+cells	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+were	O
+treated	O
+with	O
+250	O
+mg	O
+of	O
+lipoxidase	O
+and	O
+visualized	O
+by	O
+Electron	O
+Microscopy	O
+.	O
+
+Intact	O
+membranes	O
+were	O
+observed	O
+in	O
+cultures	O
+of	O
+B31A3	O
+grown	O
+under	O
+anaerobic	O
+and	O
+microaerobic	O
+conditions	O
+(	O
+Fig	O
+.	O
+6A	O
+and	O
+B	O
+respectively	O
+)	O
+.	O
+
+However	O
+,	O
+in	O
+cultures	O
+treated	O
+with	O
+lipoxidase	O
+(	O
+Fig	O
+.	O
+6C	O
+)	O
+,	O
+a	O
+significant	O
+number	O
+of	O
+membrane	O
+blebs	O
+were	O
+seen	O
+surrounding	O
+the	O
+spirochetes	O
+,	O
+indicating	O
+membrane	O
+damage	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+indicated	O
+that	O
+Borrelia	O
+membranes	O
+were	O
+a	O
+target	O
+for	O
+oxidative	O
+stress	O
+.	O
+
+Discussion	O
+
+Most	O
+bacterial	O
+pathogens	O
+are	O
+faced	O
+with	O
+the	O
+challenge	O
+of	O
+overcoming	O
+ROS	O
+generated	O
+by	O
+the	O
+host	O
+immune	O
+system	O
+.	O
+
+These	O
+radicals	O
+can	O
+cause	O
+a	O
+great	O
+deal	O
+of	O
+damage	O
+to	O
+biological	O
+molecules	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+The	O
+potential	O
+cellular	O
+targets	O
+for	O
+ROS	O
+damage	O
+in	O
+bacteria	O
+include	O
+DNA	O
+,	O
+RNA	O
+,	O
+proteins	O
+and	O
+lipids	O
+,	O
+and	O
+extensive	O
+work	O
+has	O
+been	O
+done	O
+to	O
+determine	O
+the	O
+cellular	O
+targets	O
+of	O
+ROS	O
+that	O
+affect	O
+bacterial	O
+survival	O
+.	O
+
+To	O
+date	O
+,	O
+the	O
+most	O
+definitive	O
+work	O
+has	O
+been	O
+done	O
+on	O
+E	B
+.	I
+coli	I
+.	O
+
+It	O
+seems	O
+clear	O
+from	O
+several	O
+studies	O
+that	O
+the	O
+most	O
+physiologically	O
+relevant	O
+target	O
+of	O
+ROS	O
+in	O
+E	B
+.	I
+coli	I
+is	O
+DNA	O
+.	O
+
+The	O
+exposure	O
+to	O
+micro	O
+M	O
+concentrations	O
+of	O
+ROS	O
+(	O
+i	O
+.	O
+e	O
+.	O
+H2O2	O
+)	O
+is	O
+sufficient	O
+to	O
+cause	O
+DNA	O
+damage	O
+,	O
+inhibit	O
+DNA	O
+replication	O
+,	O
+increase	O
+the	O
+mutation	O
+rate	O
+and	O
+often	O
+lead	O
+to	O
+cell	O
+death	O
+.	O
+
+This	O
+process	O
+leading	O
+to	O
+DNA	O
+damage	O
+begins	O
+with	O
+formation	O
+of	O
+O2	O
+-	O
+and	O
+H2O2	O
+from	O
+the	O
+oxidation	O
+of	O
+flavoproteins	O
+and	O
+/	O
+or	O
+the	O
+diffusion	O
+of	O
+these	O
+reactive	O
+species	O
+from	O
+the	O
+extracellular	O
+milieu	O
+.	O
+
+The	O
+subsequent	O
+oxidation	O
+of	O
+Fe	O
+-	O
+S	O
+proteins	O
+by	O
+ROS	O
+(	O
+e	O
+.	O
+g	O
+.	O
+O2	O
+-	O
+)	O
+leads	O
+to	O
+an	O
+increase	O
+in	O
+intracellular	O
+'	O
+free	O
+'	O
+Fe2	O
++	O
+which	O
+triggers	O
+the	O
+reduction	O
+of	O
+H2O2	O
+to	O
+OH	O
+(	O
+Fenton	O
+reaction	O
+)	O
+.	O
+
+The	O
+highly	O
+reactive	O
+nature	O
+of	O
+OH	O
+limits	O
+its	O
+diffusion	O
+so	O
+that	O
+it	O
+generally	O
+reacts	O
+with	O
+molecules	O
+in	O
+close	O
+proximity	O
+to	O
+its	O
+origin	O
+(	O
+e	O
+.	O
+g	O
+.	O
+the	O
+Fe2	O
++	O
+associated	O
+with	O
+DNA	O
+)	O
+.	O
+
+In	O
+DNA	O
+,	O
+OH	O
+oxidizes	O
+sugar	O
+and	O
+base	O
+moieties	O
+,	O
+producing	O
+radicals	O
+which	O
+ultimately	O
+generate	O
+lesions	O
+,	O
+including	O
+base	O
+modifications	O
+,	O
+strand	O
+breaks	O
+and	O
+chemical	O
+cross	O
+-	O
+links	O
+to	O
+other	O
+molecules	O
+.	O
+
+Base	O
+modifications	O
+lead	O
+to	O
+mismatching	O
+and	O
+increased	O
+mutation	O
+frequencies	O
+while	O
+more	O
+severe	O
+damage	O
+,	O
+such	O
+as	O
+strand	O
+breaks	O
+,	O
+prevents	O
+DNA	O
+replication	O
+,	O
+contributing	O
+to	O
+OH	O
+toxicity	O
+and	O
+cell	O
+death	O
+.	O
+
+Critical	O
+to	O
+this	O
+chemical	O
+process	O
+in	O
+vivo	O
+is	O
+the	O
+presence	O
+of	O
+iron	O
+.	O
+
+No	O
+other	O
+metal	O
+or	O
+non	O
+-	O
+metal	O
+electron	O
+carrier	O
+appears	O
+to	O
+be	O
+able	O
+to	O
+univalently	O
+reduce	O
+H2O2	O
+to	O
+OH	O
+in	O
+vivo	O
+(	O
+Macomber	O
+et	O
+al	O
+.	O
+,	O
+2007	O
+)	O
+.	O
+
+These	O
+observations	O
+are	O
+critical	O
+in	O
+beginning	O
+to	O
+understand	O
+the	O
+oxidative	O
+damage	O
+/	O
+targets	O
+in	O
+B	B
+.	I
+burgdorferi	I
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+in	O
+E	B
+.	I
+coli	I
+that	O
+the	O
+free	O
+-	O
+iron	O
+pool	O
+size	O
+determines	O
+the	O
+rate	O
+of	O
+oxidative	O
+DNA	O
+damage	O
+.	O
+
+For	O
+example	O
+,	O
+in	O
+wild	O
+-	O
+type	O
+E	B
+.	I
+coli	I
+,	O
+free	O
+iron	O
+levels	O
+are	O
+estimated	O
+to	O
+be	O
+10	O
+micro	O
+M	O
+,	O
+yet	O
+H2O2	O
+is	O
+only	O
+mildly	O
+genotoxic	O
+(	O
+Keyer	O
+and	O
+Imlay	O
+,	O
+1996	O
+)	O
+.	O
+
+However	O
+,	O
+in	O
+E	B
+.	I
+coli	I
+Fur	O
+-	O
+mutants	O
+,	O
+intracellular	O
+iron	O
+concentration	O
+increases	O
+eightfold	O
+while	O
+survival	O
+is	O
+10	O
+-	O
+fold	O
+lower	O
+when	O
+cells	O
+are	O
+exposed	O
+to	O
+H2O2	O
+.	O
+
+Because	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+do	O
+not	O
+contain	O
+detectable	O
+levels	O
+of	O
+intracellular	O
+Fe	O
+,	O
+it	O
+seems	O
+unlikely	O
+that	O
+DNA	O
+is	O
+a	O
+major	O
+target	O
+for	O
+damage	O
+via	O
+the	O
+Fenton	O
+reaction	O
+in	O
+this	O
+bacterium	O
+(	O
+Posey	O
+and	O
+Gherardini	O
+,	O
+2000	O
+)	O
+.	O
+
+The	O
+experimental	O
+data	O
+present	O
+in	O
+this	O
+report	O
+suggested	O
+that	O
+this	O
+was	O
+the	O
+case	O
+.	O
+
+When	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+were	O
+exposed	O
+to	O
+high	O
+concentrations	O
+of	O
+ROS	O
+(	O
+e	O
+.	O
+g	O
+.	O
+H2O2	O
+)	O
+,	O
+there	O
+was	O
+no	O
+effect	O
+on	O
+the	O
+spontaneous	O
+mutation	O
+rate	O
+(	O
+Fig	O
+.	O
+2A	O
+)	O
+or	O
+the	O
+number	O
+of	O
+DNA	O
+lesions	O
+(	O
+AP	O
+sites	O
+or	O
+8	O
+-	O
+oxoguanine	O
+)	O
+(	O
+Fig	O
+.	O
+2B	O
+and	O
+C	O
+)	O
+.	O
+
+It	O
+should	O
+be	O
+noted	O
+that	O
+in	O
+these	O
+experiments	O
+,	O
+a	O
+wild	O
+-	O
+type	O
+strain	O
+of	O
+B	B
+.	I
+burgdorferi	I
+was	O
+used	O
+and	O
+presumably	O
+all	O
+of	O
+the	O
+endogenous	O
+oxidative	O
+stress	O
+enzymes	O
+were	O
+expressed	O
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+no	O
+DNA	O
+damage	O
+was	O
+observed	O
+because	O
+these	O
+enzymes	O
+are	O
+capable	O
+of	O
+detoxifying	O
+the	O
+cell	O
+and	O
+protecting	O
+nucleic	O
+acids	O
+from	O
+oxidation	O
+via	O
+the	O
+Fenton	O
+reaction	O
+.	O
+
+However	O
+,	O
+we	O
+do	O
+not	O
+believe	O
+this	O
+to	O
+be	O
+the	O
+case	O
+as	O
+the	O
+concentration	O
+of	O
+oxidants	O
+used	O
+in	O
+these	O
+experiments	O
+were	O
+significantly	O
+higher	O
+than	O
+concentrations	O
+known	O
+to	O
+cause	O
+DNA	O
+damage	O
+in	O
+E	B
+.	I
+coli	I
+and	O
+other	O
+pathogenic	O
+bacteria	O
+.	O
+
+The	O
+lack	O
+of	O
+detectable	O
+DNA	O
+damage	O
+in	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+under	O
+the	O
+conditions	O
+tested	O
+could	O
+be	O
+the	O
+result	O
+of	O
+very	O
+efficient	O
+DNA	O
+repair	O
+systems	O
+.	O
+
+Bacteria	O
+,	O
+such	O
+as	O
+E	B
+.	I
+coli	I
+,	O
+harbour	O
+genes	O
+encoding	O
+repair	O
+enzymes	O
+(	O
+i	O
+.	O
+e	O
+.	O
+MutM	O
+,	O
+MutY	O
+,	O
+Ung	O
+,	O
+AlkA	O
+,	O
+MutS	O
+,	O
+MutL	O
+,	O
+ExoIII	O
+,	O
+EndoVIII	O
+,	O
+PolI	O
+,	O
+RecJ	O
+)	O
+.	O
+
+Key	O
+enzymes	O
+in	O
+the	O
+repair	O
+of	O
+8	O
+-	O
+oxoguanine	O
+lesions	O
+resulting	O
+from	O
+the	O
+oxidation	O
+of	O
+DNA	O
+are	O
+the	O
+bifunctional	O
+glycosylases	O
+,	O
+such	O
+as	O
+MutM	O
+,	O
+MutY	O
+or	O
+EndoVIII	O
+.	O
+
+The	O
+first	O
+activity	O
+of	O
+these	O
+enzymes	O
+is	O
+to	O
+remove	O
+oxidized	O
+or	O
+ring	O
+-	O
+saturated	O
+bases	O
+while	O
+the	O
+second	O
+activity	O
+is	O
+to	O
+remove	O
+the	O
+resulting	O
+deoxyribose	O
+residue	O
+,	O
+generating	O
+a	O
+3	O
+'	O
+-	O
+phosphate	O
+end	O
+(	O
+Krwawicz	O
+et	O
+al	O
+.	O
+,	O
+2007	O
+)	O
+.	O
+
+This	O
+3	O
+'	O
+-	O
+P	O
+is	O
+converted	O
+to	O
+a	O
+3	O
+'	O
+-	O
+OH	O
+by	O
+various	O
+enzymes	O
+/	O
+pathways	O
+and	O
+the	O
+lesion	O
+is	O
+repaired	O
+by	O
+enzymes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+ExoIII	O
+,	O
+PolI	O
+,	O
+LigI	O
+etc	O
+.	O
+)	O
+in	O
+the	O
+short	O
+or	O
+long	O
+BER	O
+pathways	O
+(	O
+S	O
+-	O
+BER	O
+,	O
+L	O
+-	O
+BER	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+B	B
+.	I
+burgdorferi	I
+genome	O
+does	O
+not	O
+contain	O
+genes	O
+encoding	O
+homologues	O
+of	O
+MutM	O
+,	O
+MutY	O
+or	O
+EndoVIII	O
+,	O
+suggesting	O
+that	O
+it	O
+would	O
+be	O
+difficult	O
+for	O
+the	O
+cells	O
+to	O
+efficiently	O
+repair	O
+8	O
+-	O
+oxoguanine	O
+sites	O
+using	O
+this	O
+pathway	O
+.	O
+
+B	B
+.	I
+burgdorferi	I
+does	O
+harbour	O
+the	O
+genes	O
+encoding	O
+the	O
+enzymes	O
+Ung	O
+(	O
+monofunctional	O
+gylcosylase	O
+,	O
+BB0053	O
+)	O
+,	O
+MutS	O
+(	O
+BB0797	O
+,	O
+BB0098	O
+)	O
+,	O
+MutL	O
+(	O
+BB0211	O
+)	O
+,	O
+ExoIII	O
+(	O
+BB0114	O
+)	O
+,	O
+PolI	O
+(	O
+BB0548	O
+)	O
+,	O
+LigI	O
+(	O
+BB0552	O
+)	O
+and	O
+RecJ	O
+(	O
+BB0254	O
+)	O
+(	O
+Fraser	O
+et	O
+al	O
+.	O
+,	O
+1997	O
+)	O
+which	O
+are	O
+involved	O
+in	O
+excision	O
+and	O
+repair	O
+,	O
+via	O
+S	O
+-	O
+BER	O
+or	O
+L	O
+-	O
+BER	O
+,	O
+of	O
+deaminated	O
+,	O
+alkylated	O
+,	O
+methylated	O
+or	O
+mismatched	O
+bases	O
+.	O
+
+Clearly	O
+,	O
+these	O
+repair	O
+systems	O
+in	O
+B	B
+.	I
+burgdorferi	I
+do	O
+not	O
+seem	O
+as	O
+robust	O
+at	O
+defending	O
+against	O
+oxidation	O
+of	O
+DNA	O
+as	O
+those	O
+described	O
+in	O
+E	B
+.	I
+coli	I
+.	O
+
+The	O
+lack	O
+of	O
+key	O
+repair	O
+enzymes	O
+in	O
+this	O
+system	O
+may	O
+indicate	O
+that	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+is	O
+not	O
+subjected	O
+to	O
+the	O
+same	O
+challenge	O
+from	O
+ROS	O
+as	O
+is	O
+E	B
+.	I
+coli	I
+.	O
+
+In	O
+most	O
+bacteria	O
+,	O
+ROS	O
+-	O
+mediated	O
+damage	O
+to	O
+lipids	O
+(	O
+lipid	O
+peroxidation	O
+)	O
+is	O
+very	O
+unlikely	O
+because	O
+of	O
+the	O
+lack	O
+of	O
+polyunsaturated	O
+fatty	O
+acids	O
+(	O
+e	O
+.	O
+g	O
+.	O
+linoleic	O
+acid	O
+)	O
+(	O
+Imlay	O
+,	O
+2003	O
+)	O
+.	O
+
+When	O
+it	O
+does	O
+occur	O
+,	O
+lipid	O
+peroxidation	O
+is	O
+initiated	O
+by	O
+the	O
+attack	O
+of	O
+free	O
+radicals	O
+on	O
+polyunsaturated	O
+fatty	O
+acids	O
+which	O
+decreases	O
+the	O
+membrane	O
+fluidity	O
+and	O
+,	O
+if	O
+these	O
+reactions	O
+propagate	O
+,	O
+lipid	O
+peroxides	O
+and	O
+their	O
+degradation	O
+products	O
+(	O
+e	O
+.	O
+g	O
+.	O
+aldehydes	O
+)	O
+in	O
+turn	O
+could	O
+damage	O
+proteins	O
+(	O
+Gutteridge	O
+and	O
+Halliwell	O
+,	O
+1990	O
+)	O
+.	O
+
+This	O
+would	O
+dramatically	O
+affect	O
+the	O
+function	O
+of	O
+transmembrane	O
+proteins	O
+and	O
+membrane	O
+-	O
+bound	O
+lipoproteins	O
+involved	O
+in	O
+the	O
+maintenance	O
+of	O
+membrane	O
+potential	O
+and	O
+solute	O
+transport	O
+,	O
+decreasing	O
+cell	O
+survivability	O
+.	O
+
+In	O
+contrast	O
+to	O
+most	O
+bacteria	O
+,	O
+B	B
+.	I
+burgdorferi	I
+membranes	O
+contained	O
+significant	O
+levels	O
+of	O
+unsaturated	O
+fatty	O
+acids	O
+,	O
+such	O
+as	O
+linoleic	O
+acid	O
+and	O
+linolenic	O
+acid	O
+,	O
+which	O
+were	O
+derived	O
+from	O
+the	O
+growth	O
+media	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Thus	O
+,	O
+it	O
+seemed	O
+possible	O
+that	O
+lipids	O
+and	O
+/	O
+or	O
+proteins	O
+rather	O
+than	O
+DNA	O
+are	O
+the	O
+primary	O
+targets	O
+of	O
+ROS	O
+in	O
+B	B
+.	I
+burgdorferi	I
+.	O
+
+When	O
+Borrelia	O
+cells	O
+are	O
+treated	O
+with	O
+oxidants	O
+,	O
+the	O
+levels	O
+of	O
+linoleic	O
+acid	O
+decreased	O
+while	O
+other	O
+fatty	O
+acids	O
+remain	O
+unaffected	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+HPLC	O
+-	O
+based	O
+assays	O
+demonstrated	O
+that	O
+,	O
+as	O
+linoleic	O
+acid	O
+concentrations	O
+decrease	O
+,	O
+MDA	O
+(	O
+a	O
+toxic	O
+lipid	O
+peroxide	O
+intermediate	O
+)	O
+increased	O
+(	O
+Fig	O
+.	O
+3	O
+)	O
+.	O
+
+When	O
+these	O
+cells	O
+were	O
+examined	O
+by	O
+electron	O
+microscopy	O
+,	O
+damage	O
+to	O
+the	O
+membranes	O
+(	O
+membrane	O
+'	O
+blebs	O
+'	O
+)	O
+was	O
+observed	O
+(	O
+Fig	O
+.	O
+6	O
+)	O
+.	O
+
+These	O
+data	O
+indicated	O
+that	O
+unlike	O
+most	O
+other	O
+bacteria	O
+,	O
+Borrelia	O
+membranes	O
+were	O
+damaged	O
+by	O
+oxygen	O
+radicals	O
+.	O
+
+As	O
+B	B
+.	I
+burgdorferi	I
+may	O
+be	O
+exposed	O
+to	O
+potentially	O
+harmful	O
+oxygen	O
+species	O
+at	O
+different	O
+stages	O
+of	O
+the	O
+infective	O
+cycle	O
+,	O
+the	O
+ability	O
+to	O
+protect	O
+its	O
+membrane	O
+lipids	O
+from	O
+ROS	O
+should	O
+be	O
+required	O
+for	O
+survival	O
+in	O
+the	O
+different	O
+host	O
+environments	O
+.	O
+
+In	O
+eukaryotic	O
+cells	O
+,	O
+where	O
+lipid	O
+peroxidation	O
+is	O
+a	O
+major	O
+consequence	O
+of	O
+oxidative	O
+attack	O
+,	O
+proteins	O
+which	O
+protect	O
+membranes	O
+have	O
+been	O
+well	O
+studied	O
+.	O
+
+For	O
+example	O
+,	O
+phospholipid	O
+hydroperoxide	O
+glutathione	O
+peroxidase	O
+,	O
+a	O
+member	O
+of	O
+the	O
+glutathione	O
+peroxidase	O
+family	O
+,	O
+has	O
+been	O
+identified	O
+in	O
+a	O
+variety	O
+of	O
+higher	O
+organisms	O
+.	O
+
+These	O
+enzymes	O
+are	O
+capable	O
+of	O
+reducing	O
+an	O
+assortment	O
+of	O
+hydroperoxy	O
+lipids	O
+,	O
+including	O
+oxidized	O
+phospholipids	O
+and	O
+cholesterol	O
+esters	O
+(	O
+Ursini	O
+and	O
+Bindoli	O
+,	O
+1987	O
+)	O
+,	O
+and	O
+protect	O
+complex	O
+membranes	O
+from	O
+oxidative	O
+damage	O
+.	O
+
+Much	O
+less	O
+is	O
+known	O
+about	O
+the	O
+enzyme	O
+(	O
+s	O
+)	O
+responsible	O
+for	O
+protecting	O
+unsaturated	O
+lipids	O
+from	O
+ROS	O
+in	O
+prokaryotes	O
+.	O
+
+In	O
+H	B
+.	I
+pylori	I
+,	O
+lipid	O
+hydroperoxide	O
+levels	O
+in	O
+ahpC	O
+mutants	O
+are	O
+approximately	O
+three	O
+times	O
+higher	O
+than	O
+in	O
+wild	O
+-	O
+type	O
+cells	O
+,	O
+suggesting	O
+a	O
+role	O
+for	O
+AhpC	O
+in	O
+reducing	O
+organic	O
+peroxides	O
+(	O
+Wang	O
+et	O
+al	O
+.	O
+,	O
+2006a	O
+,	O
+b	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+purified	O
+AhpC	O
+has	O
+been	O
+shown	O
+to	O
+reduce	O
+linoleic	O
+acid	O
+hydroperoxide	O
+in	O
+vitro	O
+(	O
+Baker	O
+et	O
+al	O
+.	O
+,	O
+2001	O
+)	O
+.	O
+
+Because	O
+these	O
+antioxidant	O
+enzymes	O
+promote	O
+the	O
+in	O
+vivo	O
+survival	O
+of	O
+cells	O
+when	O
+challenged	O
+with	O
+ROS	O
+,	O
+enzymes	O
+for	O
+the	O
+reduction	O
+of	O
+lipid	O
+peroxides	O
+in	O
+Borrelia	O
+need	O
+to	O
+be	O
+identified	O
+.	O
+
+Interestingly	O
+,	O
+Borrelia	O
+cells	O
+grown	O
+aerobically	O
+showed	O
+signs	O
+of	O
+membrane	O
+damage	O
+similar	O
+to	O
+those	O
+observed	O
+in	O
+cells	O
+exposed	O
+to	O
+various	O
+oxidants	O
+.	O
+
+The	O
+amount	O
+of	O
+MDA	O
+in	O
+untreated	O
+aerobically	O
+grown	O
+cells	O
+was	O
+equivalent	O
+to	O
+that	O
+observed	O
+in	O
+treated	O
+cells	O
+(	O
+Fig	O
+.	O
+3	O
+)	O
+.	O
+
+Also	O
+,	O
+EM	O
+indicated	O
+that	O
+cells	O
+grown	O
+microaerobically	O
+or	O
+aerobically	O
+had	O
+significantly	O
+more	O
+membrane	O
+damage	O
+than	O
+cells	O
+grown	O
+anaerobically	O
+(	O
+Fig	O
+.	O
+6	O
+)	O
+.	O
+
+This	O
+indicated	O
+that	O
+Borrelia	O
+membranes	O
+can	O
+be	O
+damaged	O
+simply	O
+by	O
+exposure	O
+to	O
+physiologically	O
+relevant	O
+concentrations	O
+of	O
+dissolved	O
+oxygen	O
+.	O
+
+In	O
+exponentially	O
+growing	O
+E	B
+.	I
+coli	I
+,	O
+Imlay	O
+and	O
+Fridovich	O
+(	O
+1991	O
+)	O
+have	O
+shown	O
+that	O
+both	O
+O2	O
+-	O
+and	O
+H2O2	O
+are	O
+generated	O
+by	O
+the	O
+autoxidation	O
+of	O
+components	O
+of	O
+the	O
+respiratory	O
+chain	O
+during	O
+oxygen	O
+metabolism	O
+.	O
+
+In	O
+contrast	O
+,	O
+B	B
+.	I
+burgdorferi	I
+is	O
+very	O
+metabolically	O
+limited	O
+and	O
+has	O
+no	O
+enzymes	O
+for	O
+the	O
+TCA	O
+cycle	O
+or	O
+respiration	O
+.	O
+
+Therefore	O
+,	O
+it	O
+seems	O
+more	O
+likely	O
+that	O
+sources	O
+of	O
+ROS	O
+are	O
+exogenous	O
+(	O
+e	O
+.	O
+g	O
+.	O
+innate	O
+immune	O
+response	O
+in	O
+the	O
+mammalian	O
+host	O
+)	O
+rather	O
+than	O
+endogenous	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+current	O
+practice	O
+of	O
+growing	O
+B	B
+.	I
+burgdorferi	I
+under	O
+atmospheric	O
+oxygen	O
+could	O
+itself	O
+be	O
+unintentionally	O
+compromising	O
+cell	O
+integrity	O
+during	O
+in	O
+vitro	O
+manipulations	O
+.	O
+
+Analyses	O
+of	O
+the	O
+B	B
+.	I
+burgdorferi	I
+genome	O
+indicates	O
+that	O
+only	O
+a	O
+few	O
+genes	O
+encoding	O
+putative	O
+oxidative	O
+stress	O
+/	O
+intracellular	O
+redox	O
+proteins	O
+(	O
+SodA	O
+,	O
+NapA	O
+,	O
+BosR	O
+,	O
+CoADR	O
+,	O
+Trx	O
+and	O
+TrxR	O
+)	O
+(	O
+Fraser	O
+et	O
+al	O
+.	O
+,	O
+1997	O
+)	O
+are	O
+present	O
+,	O
+compared	O
+with	O
+other	O
+bacterial	O
+pathogens	O
+,	O
+including	O
+other	O
+pathogenic	O
+spirochetes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+Treponema	O
+,	O
+Leptospira	O
+)	O
+.	O
+
+Despite	O
+this	O
+apparent	O
+'	O
+deficiency	O
+'	O
+in	O
+the	O
+number	O
+of	O
+ROS	O
+-	O
+protective	O
+enzymes	O
+,	O
+B	B
+.	I
+burgdorferi	I
+cells	O
+appear	O
+to	O
+be	O
+able	O
+to	O
+cope	O
+with	O
+physiologically	O
+relevant	O
+levels	O
+of	O
+ROS	O
+.	O
+
+There	O
+are	O
+several	O
+factors	O
+that	O
+would	O
+contribute	O
+to	O
+this	O
+phenomenon	O
+:	O
+(	O
+i	O
+)	O
+as	O
+B	B
+.	I
+burgdorferi	I
+does	O
+not	O
+harbour	O
+the	O
+genes	O
+encoding	O
+respiratory	O
+enzymes	O
+nor	O
+metabolize	O
+oxygen	O
+,	O
+it	O
+seems	O
+unlikely	O
+that	O
+significant	O
+levels	O
+of	O
+ROS	O
+are	O
+generated	O
+via	O
+the	O
+incomplete	O
+reduction	O
+of	O
+O2	O
+during	O
+cellular	O
+metabolism	O
+.	O
+
+This	O
+would	O
+suggest	O
+that	O
+potential	O
+ROS	O
+challenges	O
+to	O
+B	B
+.	I
+burgdorferi	I
+would	O
+come	O
+almost	O
+completely	O
+from	O
+extracellular	O
+sources	O
+with	O
+little	O
+contribution	O
+from	O
+intracellularly	O
+generated	O
+ROS	O
+;	O
+(	O
+ii	O
+)	O
+owing	O
+to	O
+a	O
+lack	O
+of	O
+understanding	O
+of	O
+the	O
+physiological	O
+conditions	O
+in	O
+vector	O
+and	O
+host	O
+tissues	O
+infected	O
+with	O
+B	B
+.	I
+burgdorferi	I
+,	O
+it	O
+is	O
+difficult	O
+to	O
+assess	O
+the	O
+levels	O
+and	O
+/	O
+or	O
+sites	O
+of	O
+the	O
+potential	O
+ROS	O
+challenge	O
+during	O
+the	O
+infective	O
+cycle	O
+and	O
+(	O
+iii	O
+)	O
+most	O
+importantly	O
+,	O
+analyses	O
+of	O
+the	O
+potential	O
+targets	O
+for	O
+ROS	O
+in	O
+B	B
+.	I
+burgdorferi	I
+strongly	O
+suggested	O
+that	O
+the	O
+major	O
+targets	O
+of	O
+oxidative	O
+damage	O
+are	O
+different	O
+and	O
+perhaps	O
+less	O
+extensive	O
+in	O
+this	O
+bacterium	O
+than	O
+in	O
+other	O
+bacterial	O
+pathogens	O
+(	O
+e	O
+.	O
+g	O
+.	O
+E	B
+.	I
+coli	I
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+this	O
+suggests	O
+that	O
+B	B
+.	I
+burgdorferi	I
+would	O
+be	O
+innately	O
+more	O
+resistant	O
+to	O
+ROS	O
+and	O
+require	O
+a	O
+less	O
+extensive	O
+repertoire	O
+of	O
+enzymes	O
+to	O
+protect	O
+the	O
+cells	O
+from	O
+oxidative	O
+damage	O
+.	O
+
+Experimental	O
+procedures	O
+
+Strains	O
+,	O
+growth	O
+conditions	O
+and	O
+reagents	O
+
+Borrelia	B
+burgdorferi	I
+strain	O
+B31A3	O
+and	O
+strain	O
+B314	O
+(	O
+Sadziene	O
+et	O
+al	O
+.	O
+,	O
+1993	O
+)	O
+were	O
+grown	O
+in	O
+modified	O
+BSK	O
+-	O
+II	O
+(	O
+Barbour	O
+,	O
+1984	O
+)	O
+medium	O
+at	O
+34	O
+degrees	O
+C	O
+under	O
+an	O
+atmosphere	O
+of	O
+0	O
+-	O
+20	O
+%	O
+O2	O
+with	O
+5	O
+%	O
+CO2	O
+and	O
+the	O
+balance	O
+N2	O
+.	O
+
+Cells	O
+density	O
+was	O
+determined	O
+using	O
+a	O
+dark	O
+-	O
+field	O
+microscope	O
+.	O
+
+All	O
+reagents	O
+were	O
+purchased	O
+from	O
+Sigma	O
+Chemicals	O
+,	O
+St	O
+.	O
+
+Louis	O
+,	O
+MO	O
+unless	O
+stated	O
+otherwise	O
+.	O
+
+E	B
+.	I
+coli	I
+strain	O
+Top10	O
+,	O
+strain	O
+TA4315	O
+(	O
+ahpCF	O
+)	O
+(	O
+Storz	O
+et	O
+al	O
+.	O
+,	O
+1989	O
+)	O
+and	O
+CM1319	O
+(	O
+mutM	O
+)	O
+(	O
+Bridges	O
+et	O
+al	O
+.	O
+,	O
+1996	O
+)	O
+were	O
+grown	O
+in	O
+Luria	O
+-	O
+Bertani	O
+(	O
+LB	O
+)	O
+at	O
+37	O
+degrees	O
+C	O
+with	O
+shaking	O
+.	O
+
+Per	O
+cent	O
+survivability	O
+assays	O
+
+Borrelia	B
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+grown	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+in	O
+BSK	O
+II	O
+under	O
+microaerobic	O
+(	O
+3	O
+%	O
+O2	O
+)	O
+conditions	O
+,	O
+the	O
+culture	O
+split	O
+and	O
+the	O
+cells	O
+treated	O
+with	O
+varying	O
+concentrations	O
+of	O
+oxidants	O
+(	O
+0	O
+-	O
+50	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+or	O
+H2O2	O
+)	O
+at	O
+34	O
+degrees	O
+C	O
+for	O
+4	O
+h	O
+.	O
+
+After	O
+the	O
+incubation	O
+,	O
+cells	O
+were	O
+diluted	O
+in	O
+fresh	O
+BSK	O
+II	O
+,	O
+plated	O
+on	O
+BSK	O
+plates	O
+and	O
+incubated	O
+7	O
+-	O
+14	O
+days	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+Per	O
+cent	O
+survivability	O
+was	O
+calculated	O
+as	O
+the	O
+number	O
+of	O
+colonies	O
+on	O
+the	O
+treated	O
+plates	O
+versus	O
+the	O
+number	O
+of	O
+colonies	O
+on	O
+the	O
+untreated	O
+plates	O
+.	O
+
+Determination	O
+of	O
+the	O
+spontaneous	O
+mutation	O
+rate	O
+
+To	O
+determine	O
+spontaneous	O
+resistance	O
+to	O
+coumermycin	O
+A1	O
+,	O
+B	B
+.	I
+burgdorferi	I
+B31A3	O
+cells	O
+were	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+and	O
+treated	O
+with	O
+5	O
+mM	O
+H2O2	O
+for	O
+1	O
+h	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+The	O
+cells	O
+were	O
+plated	O
+on	O
+BSK	O
+plates	O
+containing	O
+0	O
+or	O
+250	O
+ng	O
+ml	O
+-	O
+1	O
+coumermycin	O
+A1	O
+and	O
+incubated	O
+7	O
+-	O
+14	O
+days	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+The	O
+resistance	O
+frequency	O
+was	O
+calculated	O
+as	O
+the	O
+number	O
+of	O
+colonies	O
+that	O
+are	O
+CouR	O
+per	O
+total	O
+number	O
+of	O
+cells	O
+plated	O
+.	O
+
+Measurement	O
+of	O
+DNA	O
+base	O
+lesions	O
+
+Borrelia	B
+burgdorferi	I
+B31A3	O
+cells	O
+were	O
+grown	O
+in	O
+BSK	O
+-	O
+II	O
+under	O
+microaerobic	O
+conditions	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+,	O
+treated	O
+with	O
+various	O
+oxidants	O
+(	O
+1	O
+or	O
+10	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+,	O
+1	O
+or	O
+10	O
+mM	O
+H2O2	O
+,	O
+10	O
+mM	O
+paraquat	O
+or	O
+lipoxidase	O
+)	O
+for	O
+4	O
+h	O
+and	O
+total	O
+DNA	O
+was	O
+isolated	O
+using	O
+Wizard	O
+Genomic	O
+DNA	O
+Purification	O
+Kit	O
+(	O
+Promega	O
+Corp	O
+.	O
+,	O
+Madison	O
+,	O
+WI	O
+)	O
+.	O
+
+The	O
+number	O
+of	O
+base	O
+lesions	O
+was	O
+determined	O
+using	O
+the	O
+DNA	O
+Damage	O
+Quantification	O
+Colorimetric	O
+Assay	O
+kit	O
+(	O
+Oxford	O
+Biomedical	O
+Research	O
+,	O
+Oxford	O
+,	O
+MI	O
+)	O
+following	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+Briefly	O
+,	O
+500	O
+ng	O
+of	O
+DNA	O
+was	O
+mixed	O
+with	O
+an	O
+equal	O
+volume	O
+of	O
+10	O
+mM	O
+biotinylated	O
+aldehyde	O
+reactive	O
+probe	O
+(	O
+ARP	O
+)	O
+reagent	O
+and	O
+incubated	O
+for	O
+1	O
+h	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+The	O
+DNA	O
+-	O
+ARP	O
+product	O
+was	O
+ethanol	O
+-	O
+precipitated	O
+using	O
+glycogen	O
+as	O
+a	O
+carrier	O
+,	O
+washed	O
+three	O
+times	O
+with	O
+70	O
+%	O
+ethanol	O
+and	O
+resuspended	O
+in	O
+Tris	O
+-	O
+EDTA	O
+to	O
+give	O
+a	O
+final	O
+concentration	O
+of	O
+0	O
+.	O
+5	O
+micro	O
+g	O
+ml	O
+-	O
+1	O
+.	O
+
+The	O
+DNA	O
+-	O
+ARP	O
+product	O
+was	O
+allowed	O
+to	O
+bind	O
+to	O
+the	O
+wells	O
+of	O
+96	O
+-	O
+well	O
+microplate	O
+overnight	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+After	O
+the	O
+binding	O
+,	O
+the	O
+wells	O
+were	O
+washed	O
+four	O
+times	O
+with	O
+TPBS	O
+(	O
+137	O
+mM	O
+NaCl	O
+,	O
+2	O
+.	O
+7	O
+mM	O
+KCl	O
+,	O
+10	O
+mM	O
+Na3HPO4	O
+,	O
+2	O
+mM	O
+KH2PO4	O
+,	O
+0	O
+.	O
+5	O
+%	O
+Tween	O
+20	O
+,	O
+pH	O
+7	O
+.	O
+4	O
+)	O
+.	O
+
+The	O
+HRP	O
+-	O
+streptavidin	O
+conjugate	O
+was	O
+diluted	O
+to	O
+0	O
+.	O
+5	O
+micro	O
+g	O
+ml	O
+-	O
+1	O
+in	O
+Assay	O
+Buffer	O
+(	O
+0	O
+.	O
+15	O
+M	O
+NaCl	O
+,	O
+10	O
+mM	O
+NasHPO4	O
+,	O
+1	O
+.	O
+5	O
+mM	O
+KH2PO4	O
+,	O
+2	O
+.	O
+5	O
+mM	O
+KCl	O
+,	O
+5	O
+mg	O
+ml	O
+-	O
+1	O
+BSA	O
+,	O
+0	O
+.	O
+1	O
+%	O
+Tween	O
+,	O
+pH	O
+7	O
+.	O
+5	O
+)	O
+,	O
+100	O
+micro	O
+l	O
+was	O
+added	O
+to	O
+each	O
+well	O
+and	O
+the	O
+plate	O
+incubated	O
+at	O
+100	O
+r	O
+.	O
+p	O
+.	O
+m	O
+.	O
+for	O
+1	O
+h	O
+at	O
+room	O
+temperature	O
+(	O
+RT	O
+)	O
+.	O
+
+After	O
+incubation	O
+,	O
+the	O
+wells	O
+were	O
+washed	O
+four	O
+times	O
+with	O
+TPBS	O
+,	O
+100	O
+micro	O
+l	O
+of	O
+substrate	O
+was	O
+added	O
+to	O
+each	O
+well	O
+and	O
+incubated	O
+for	O
+1	O
+h	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+The	O
+reaction	O
+was	O
+then	O
+quenched	O
+with	O
+100	O
+micro	O
+l	O
+of	O
+1	O
+M	O
+sulphuric	O
+acid	O
+and	O
+the	O
+reaction	O
+was	O
+monitored	O
+at	O
+450	O
+nm	O
+.	O
+
+The	O
+number	O
+of	O
+aldehyde	O
+reactive	O
+probe	O
+(	O
+DNA	O
+base	O
+lesions	O
+)	O
+per	O
+105	O
+bp	O
+DNA	O
+was	O
+determined	O
+using	O
+a	O
+standard	O
+curve	O
+.	O
+
+As	O
+a	O
+control	O
+,	O
+E	B
+.	I
+coli	I
+TA4315	O
+cells	O
+were	O
+grown	O
+in	O
+minimal	O
+media	O
+to	O
+OD600	O
+of	O
+0	O
+.	O
+4	O
+,	O
+treated	O
+with	O
+0	O
+or	O
+100	O
+micro	O
+M	O
+H2O2	O
+for	O
+30	O
+min	O
+and	O
+DNA	O
+isolated	O
+.	O
+
+The	O
+number	O
+of	O
+base	O
+lesions	O
+was	O
+determined	O
+as	O
+described	O
+above	O
+.	O
+
+B	B
+.	I
+burgdorferi	I
+strain	O
+B314	O
+cells	O
+were	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+and	O
+DNA	O
+isolated	O
+.	O
+
+The	O
+number	O
+of	O
+DNA	O
+lesions	O
+was	O
+determined	O
+as	O
+described	O
+.	O
+
+To	O
+determine	O
+the	O
+amount	O
+of	O
+8	O
+-	O
+oxoguanine	O
+in	O
+B	B
+.	I
+burgdorferi	I
+DNA	O
+,	O
+cells	O
+were	O
+grown	O
+and	O
+treated	O
+as	O
+described	O
+above	O
+and	O
+DNA	O
+isolated	O
+.	O
+
+The	O
+DNA	O
+was	O
+converted	O
+to	O
+single	O
+-	O
+stranded	O
+DNA	O
+by	O
+boiling	O
+the	O
+sample	O
+for	O
+5	O
+min	O
+followed	O
+by	O
+rapid	O
+chill	O
+on	O
+ice	O
+.	O
+
+The	O
+DNA	O
+was	O
+then	O
+digested	O
+with	O
+nuclease	O
+P1	O
+for	O
+2	O
+h	O
+and	O
+then	O
+treated	O
+with	O
+alkaline	O
+phosphatase	O
+for	O
+1	O
+h	O
+following	O
+manufacturer	O
+'	O
+s	O
+protocols	O
+.	O
+
+The	O
+resultant	O
+mixture	O
+was	O
+then	O
+centrifuged	O
+for	O
+5	O
+min	O
+at	O
+6000	O
+g	O
+and	O
+the	O
+supernatant	O
+used	O
+for	O
+the	O
+8	O
+-	O
+oxoguanine	O
+ELISA	O
+assay	O
+(	O
+Oxford	O
+Biomedical	O
+Research	O
+,	O
+Oxford	O
+,	O
+MI	O
+)	O
+.	O
+
+As	O
+a	O
+control	O
+,	O
+E	B
+.	I
+coli	I
+CM1319	O
+(	O
+mutM	O
+)	O
+cells	O
+were	O
+grown	O
+in	O
+LB	O
+to	O
+OD600	O
+of	O
+0	O
+.	O
+4	O
+,	O
+treated	O
+with	O
+0	O
+or	O
+100	O
+micro	O
+M	O
+H2O2	O
+for	O
+1	O
+h	O
+and	O
+DNA	O
+isolated	O
+.	O
+
+The	O
+concentration	O
+of	O
+8	O
+-	O
+oxoguanine	O
+was	O
+determined	O
+as	O
+above	O
+.	O
+
+Lipid	O
+analyses	O
+
+To	O
+determine	O
+fatty	O
+acid	O
+content	O
+in	O
+B	B
+.	I
+burgdorferi	I
+total	O
+membranes	O
+,	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+grown	O
+under	O
+anaerobic	O
+conditions	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+,	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+5000	O
+g	O
+,	O
+15	O
+min	O
+,	O
+4	O
+degrees	O
+C	O
+)	O
+and	O
+washed	O
+two	O
+times	O
+with	O
+HN	O
+(	O
+20	O
+mM	O
+NaCl	O
+,	O
+50	O
+mM	O
+Hepes	O
+,	O
+pH	O
+7	O
+.	O
+6	O
+)	O
+buffer	O
+.	O
+
+Cell	O
+pellets	O
+were	O
+analysed	O
+for	O
+fatty	O
+acid	O
+composition	O
+by	O
+fatty	O
+acid	O
+methyl	O
+ester	O
+(	O
+FAME	O
+)	O
+gas	O
+chromatography	O
+(	O
+Lipid	O
+Technologies	O
+,	O
+Austin	O
+,	O
+MN	O
+)	O
+and	O
+results	O
+are	O
+reported	O
+as	O
+percentage	O
+of	O
+total	O
+fatty	O
+acid	O
+content	O
+.	O
+
+To	O
+determine	O
+the	O
+effects	O
+of	O
+oxidants	O
+on	O
+fatty	O
+acid	O
+composition	O
+,	O
+a	O
+1	O
+.	O
+5	O
+l	O
+culture	O
+of	O
+B	B
+.	I
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+grown	O
+under	O
+microaerobic	O
+conditions	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+.	O
+
+The	O
+culture	O
+was	O
+split	O
+into	O
+500	O
+ml	O
+aliquots	O
+,	O
+the	O
+first	O
+was	O
+treated	O
+with	O
+1	O
+mM	O
+t	O
+-	O
+butyl	O
+hydroperoxide	O
+,	O
+the	O
+second	O
+with	O
+0	O
+.	O
+25	O
+mg	O
+of	O
+lipoxidase	O
+(	O
+17	O
+700	O
+units	O
+)	O
+and	O
+the	O
+third	O
+was	O
+untreated	O
+.	O
+
+All	O
+cultures	O
+were	O
+incubated	O
+for	O
+12	O
+h	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+Cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+5000	O
+g	O
+,	O
+4	O
+degrees	O
+C	O
+,	O
+15	O
+min	O
+)	O
+and	O
+washed	O
+three	O
+times	O
+with	O
+HN	O
+buffer	O
+.	O
+
+The	O
+fatty	O
+acids	O
+present	O
+in	O
+the	O
+cell	O
+pellets	O
+were	O
+analysed	O
+by	O
+FAME	O
+gas	O
+chromatography	O
+(	O
+Industrial	O
+Laboratory	O
+,	O
+Wheat	O
+Ridge	O
+,	O
+CO	O
+)	O
+.	O
+
+Fatty	O
+acids	O
+were	O
+reported	O
+as	O
+percentage	O
+of	O
+total	O
+cell	O
+mass	O
+.	O
+
+Measurement	O
+of	O
+MDA	O
+
+Borrelia	B
+burgdorferi	I
+strain	O
+B31A3	O
+was	O
+grown	O
+aerobically	O
+,	O
+microaerobically	O
+and	O
+anaerobically	O
+as	O
+described	O
+above	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+.	O
+
+The	O
+microaerobic	O
+culture	O
+was	O
+split	O
+and	O
+treated	O
+with	O
+either	O
+5	O
+mM	O
+AAPH	O
+[	O
+2	O
+,	O
+2	O
+'	O
+-	O
+azobis	O
+(	O
+2	O
+-	O
+methylpropionamidine	O
+)	O
+dihydrochloride	O
+]	O
+or	O
+250	O
+mg	O
+of	O
+lipoxidase	O
+for	O
+4	O
+h	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+To	O
+measure	O
+the	O
+amount	O
+of	O
+MDA	O
+,	O
+the	O
+cells	O
+were	O
+derivatized	O
+with	O
+thiobarbituric	O
+acid	O
+and	O
+analysed	O
+by	O
+HPLC	O
+as	O
+described	O
+by	O
+Seljeskog	O
+et	O
+al	O
+.	O
+
+(	O
+2006	O
+)	O
+.	O
+
+After	O
+the	O
+incubation	O
+,	O
+all	O
+cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+1000	O
+g	O
+,	O
+5	O
+min	O
+,	O
+4	O
+degrees	O
+C	O
+)	O
+and	O
+washed	O
+three	O
+times	O
+with	O
+HN	O
+buffer	O
+.	O
+
+Each	O
+sample	O
+was	O
+resuspended	O
+in	O
+50	O
+micro	O
+l	O
+of	O
+HN	O
+,	O
+mixed	O
+with	O
+150	O
+micro	O
+l	O
+of	O
+0	O
+.	O
+1	O
+N	O
+perchloric	O
+acid	O
+,	O
+150	O
+micro	O
+l	O
+of	O
+40	O
+mM	O
+thiobarbituric	O
+acid	O
+and	O
+35	O
+micro	O
+l	O
+of	O
+20	O
+%	O
+SDS	O
+,	O
+vortexed	O
+and	O
+heated	O
+at	O
+97	O
+degrees	O
+C	O
+for	O
+60	O
+min	O
+.	O
+
+After	O
+cooling	O
+at	O
+-	O
+20	O
+degrees	O
+C	O
+for	O
+20	O
+min	O
+,	O
+300	O
+micro	O
+l	O
+of	O
+methanol	O
+and	O
+100	O
+micro	O
+l	O
+of	O
+20	O
+%	O
+trichloroacetic	O
+acid	O
+was	O
+added	O
+and	O
+the	O
+samples	O
+were	O
+mixed	O
+vigorously	O
+and	O
+centrifuged	O
+(	O
+13	O
+000	O
+g	O
+,	O
+6	O
+min	O
+)	O
+.	O
+
+The	O
+samples	O
+(	O
+10	O
+micro	O
+l	O
+)	O
+were	O
+then	O
+analysed	O
+with	O
+an	O
+Agilent	O
+Technologies	O
+1200	O
+series	O
+HPLC	O
+system	O
+using	O
+a	O
+C18	O
+4	O
+.	O
+6	O
+x	O
+150	O
+mm	O
+column	O
+with	O
+mobile	O
+phase	O
+72	O
+:	O
+17	O
+:	O
+11	O
+(	O
+50	O
+mM	O
+KPO4	O
+,	O
+pH	O
+6	O
+.	O
+8	O
+:	O
+methanol	O
+:	O
+acetonitrile	O
+)	O
+.	O
+
+Absorbance	O
+was	O
+monitored	O
+at	O
+532	O
+nm	O
+.	O
+
+Pure	O
+MDA	O
+standards	O
+(	O
+0	O
+-	O
+10	O
+micro	O
+M	O
+)	O
+were	O
+prepared	O
+in	O
+methanol	O
+for	O
+comparison	O
+.	O
+
+As	O
+a	O
+negative	O
+control	O
+,	O
+E	B
+.	I
+coli	I
+Top10	O
+cells	O
+were	O
+grown	O
+to	O
+OD600	O
+of	O
+0	O
+.	O
+4	O
+,	O
+treated	O
+with	O
+0	O
+or	O
+5	O
+mM	O
+AAPH	O
+for	O
+30	O
+min	O
+and	O
+MDA	O
+measured	O
+as	O
+above	O
+.	O
+
+As	O
+a	O
+positive	O
+control	O
+,	O
+mouse	B
+myeloma	O
+SP2	O
+/	O
+O	O
+cells	O
+were	O
+cultured	O
+with	O
+HYQ	O
+-	O
+CCM1	O
+(	O
+HyClone	O
+)	O
+medium	O
+at	O
+37	O
+degrees	O
+C	O
+in	O
+a	O
+humidified	O
+5	O
+%	O
+CO2	O
+atmosphere	O
+,	O
+treated	O
+with	O
+1	O
+mM	O
+AAPH	O
+at	O
+37	O
+degrees	O
+C	O
+for	O
+4	O
+h	O
+(	O
+Chotimarkorn	O
+et	O
+al	O
+.	O
+,	O
+2005	O
+)	O
+and	O
+MDA	O
+measured	O
+as	O
+above	O
+.	O
+
+Identification	O
+of	O
+lipid	O
+damage	O
+using	O
+Diphenyl	O
+-	O
+1	O
+-	O
+pyrenylphosphine	O
+fluorescent	O
+stain	O
+
+Borrelia	B
+burgdorferi	I
+strain	O
+B31A3	O
+cells	O
+were	O
+grown	O
+microaerobically	O
+as	O
+described	O
+above	O
+until	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+was	O
+obtained	O
+.	O
+
+The	O
+culture	O
+was	O
+divided	O
+into	O
+two	O
+equal	O
+aliquots	O
+and	O
+the	O
+cells	O
+treated	O
+with	O
+5	O
+mM	O
+AAPH	O
+for	O
+4	O
+h	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+After	O
+the	O
+incubation	O
+,	O
+all	O
+cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+1000	O
+g	O
+,	O
+5	O
+min	O
+,	O
+4	O
+degrees	O
+C	O
+)	O
+and	O
+washed	O
+three	O
+times	O
+with	O
+HN	O
+buffer	O
+.	O
+
+To	O
+visualize	O
+Borrelia	O
+cells	O
+,	O
+the	O
+cells	O
+were	O
+stained	O
+with	O
+PKH26	O
+Red	O
+Fluorescent	O
+Cell	O
+Linker	O
+Dye	O
+(	O
+Sigma	O
+Aldrich	O
+)	O
+following	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+To	O
+visualize	O
+the	O
+lipid	O
+hydroperoxides	O
+in	O
+the	O
+cell	O
+membrane	O
+,	O
+the	O
+cells	O
+were	O
+counterstained	O
+with	O
+DPPP	O
+(	O
+Cayman	O
+Chemicals	O
+,	O
+MI	O
+)	O
+(	O
+Okimoto	O
+et	O
+al	O
+.	O
+,	O
+2000	O
+)	O
+.	O
+
+Briefly	O
+,	O
+after	O
+cells	O
+were	O
+stained	O
+with	O
+the	O
+Red	O
+Fluorescent	O
+dye	O
+,	O
+2	O
+ml	O
+of	O
+rabbit	B
+serum	O
+was	O
+added	O
+to	O
+stop	O
+the	O
+reaction	O
+and	O
+the	O
+mixture	O
+incubated	O
+for	O
+1	O
+min	O
+at	O
+RT	O
+.	O
+
+Next	O
+,	O
+4	O
+ml	O
+of	O
+HN	O
+buffer	O
+was	O
+added	O
+,	O
+the	O
+cells	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+1000	O
+g	O
+,	O
+10	O
+min	O
+,	O
+RT	O
+)	O
+and	O
+washed	O
+three	O
+times	O
+with	O
+HN	O
+buffer	O
+.	O
+
+The	O
+cells	O
+were	O
+then	O
+resuspended	O
+in	O
+1	O
+ml	O
+of	O
+HN	O
+buffer	O
+,	O
+incubated	O
+at	O
+34	O
+degrees	O
+C	O
+for	O
+5	O
+min	O
+and	O
+30	O
+micro	O
+l	O
+of	O
+2	O
+.	O
+5	O
+mM	O
+DPPP	O
+was	O
+added	O
+.	O
+
+The	O
+incubation	O
+was	O
+then	O
+continued	O
+at	O
+34	O
+degrees	O
+C	O
+for	O
+5	O
+min	O
+in	O
+the	O
+dark	O
+.	O
+
+After	O
+incubation	O
+,	O
+the	O
+mixture	O
+was	O
+centrifuged	O
+(	O
+1000	O
+g	O
+,	O
+10	O
+min	O
+,	O
+RT	O
+)	O
+and	O
+the	O
+cells	O
+washed	O
+three	O
+times	O
+with	O
+HN	O
+buffer	O
+.	O
+
+The	O
+cells	O
+were	O
+then	O
+resuspended	O
+in	O
+100	O
+micro	O
+l	O
+HN	O
+buffer	O
+and	O
+observed	O
+by	O
+fluorescence	O
+microscopy	O
+with	O
+excitation	O
+wavelengths	O
+551	O
+nm	O
+(	O
+Red	O
+Fluorescent	O
+)	O
+and	O
+351	O
+nm	O
+(	O
+DPPP	O
+)	O
+,	O
+and	O
+emission	O
+wavelengths	O
+567	O
+nm	O
+(	O
+Red	O
+Fluorescent	O
+)	O
+and	O
+380	O
+nm	O
+(	O
+DPPP	O
+)	O
+.	O
+
+As	O
+a	O
+positive	O
+control	O
+,	O
+mouse	B
+myeloma	O
+SP2	O
+/	O
+O	O
+cells	O
+were	O
+cultured	O
+with	O
+HYQ	O
+-	O
+CCM1	O
+(	O
+HyClone	O
+)	O
+medium	O
+at	O
+37	O
+degrees	O
+C	O
+in	O
+a	O
+humidified	O
+5	O
+%	O
+CO2	O
+atmosphere	O
+,	O
+treated	O
+with	O
+1	O
+mM	O
+AAPH	O
+at	O
+37	O
+degrees	O
+C	O
+for	O
+4	O
+h	O
+(	O
+Chotimarkorn	O
+et	O
+al	O
+.	O
+,	O
+2005	O
+)	O
+and	O
+stained	O
+as	O
+described	O
+above	O
+.	O
+
+As	O
+a	O
+negative	O
+control	O
+,	O
+E	B
+.	I
+coli	I
+Top10	O
+cells	O
+were	O
+grown	O
+to	O
+OD600	O
+of	O
+0	O
+.	O
+4	O
+,	O
+treated	O
+with	O
+0	O
+or	O
+5	O
+mM	O
+AAPH	O
+for	O
+30	O
+min	O
+and	O
+stained	O
+as	O
+described	O
+above	O
+.	O
+
+Electron	O
+microscopy	O
+
+Borrelia	B
+burgdorferi	I
+cells	O
+were	O
+grown	O
+under	O
+microaerobic	O
+or	O
+anaerobic	O
+conditions	O
+to	O
+a	O
+cell	O
+density	O
+of	O
+5	O
+x	O
+107	O
+cells	O
+ml	O
+-	O
+1	O
+.	O
+
+The	O
+microaerobic	O
+cultures	O
+were	O
+split	O
+and	O
+treated	O
+with	O
+lipoxidase	O
+for	O
+4	O
+h	O
+at	O
+34	O
+degrees	O
+C	O
+.	O
+
+Cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+(	O
+5000	O
+g	O
+,	O
+10	O
+min	O
+,	O
+4	O
+degrees	O
+C	O
+)	O
+,	O
+washed	O
+and	O
+resuspended	O
+in	O
+HBSS	O
+(	O
+Lonza	O
+Group	O
+Ltd	O
+,	O
+Switzerland	O
+)	O
+.	O
+
+The	O
+cells	O
+were	O
+fixed	O
+with	O
+Karnovsky	O
+'	O
+s	O
+phosphate	O
+for	O
+5	O
+min	O
+at	O
+RT	O
+adsorbed	O
+to	O
+Formvar	O
+/	O
+carbon	O
+-	O
+coated	O
+grids	O
+(	O
+Ted	O
+Pella	O
+,	O
+Redding	O
+,	O
+CA	O
+)	O
+for	O
+5	O
+min	O
+and	O
+washed	O
+three	O
+times	O
+in	O
+H2O	O
+.	O
+
+The	O
+grids	O
+were	O
+stained	O
+with	O
+1	O
+%	O
+ammonium	O
+molybdate	O
+and	O
+allowed	O
+to	O
+air	O
+-	O
+dry	O
+.	O
+
+Samples	O
+were	O
+examined	O
+using	O
+a	O
+Hitachi	O
+H7500	O
+electron	O
+microscope	O
+(	O
+Hitachi	O
+High	O
+Technologies	O
+America	O
+,	O
+Pleasanton	O
+,	O
+CA	O
+)	O
+.	O
+
+Cytotoxic	O
+Activity	O
+of	O
+Silyl	O
+-	O
+and	O
+Germyl	O
+-	O
+Substituted	O
+4	O
+,	O
+4	O
+-	O
+Dioxo	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+Dihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazolines	O
+-	O
+2	O
+
+Abstract	O
+
+The	O
+[	O
+2	O
++	O
+3	O
+]	O
+dipolar	O
+cycloaddition	O
+of	O
+nitrile	O
+oxides	O
+to	O
+the	O
+double	O
+C	O
+=	O
+C	O
+bonds	O
+of	O
+thiophene	O
+-	O
+1	O
+,	O
+1	O
+-	O
+dioxides	O
+leads	O
+to	O
+formation	O
+of	O
+the	O
+fused	O
+isoxazolines	O
+-	O
+2	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+Tumor	O
+growth	O
+inhibition	O
+of	O
+these	O
+compounds	O
+strongly	O
+depends	O
+on	O
+the	O
+nature	O
+of	O
+group	O
+IV	O
+A	O
+element	O
+increasing	O
+from	O
+slightly	O
+active	O
+tert	O
+-	O
+butyl	O
+derivatives	O
+to	O
+silicon	O
+and	O
+germanium	O
+containing	O
+analogues	O
+.	O
+
+The	O
+products	O
+of	O
+benzonitrile	O
+oxide	O
+cycloaddition	O
+have	O
+greater	O
+cytotoxic	O
+effect	O
+than	O
+the	O
+compounds	O
+obtained	O
+from	O
+the	O
+cycloaddition	O
+reaction	O
+of	O
+2	O
+,	O
+5	O
+-	O
+disubstituted	O
+thiophene	O
+-	O
+1	O
+,	O
+1	O
+-	O
+dioxides	O
+with	O
+acetonitrile	O
+oxide	O
+.	O
+
+Fused	O
+silyl	O
+substituted	O
+isoxazolines	O
+-	O
+2	O
+are	O
+stronger	O
+NO	O
+-	O
+inducers	O
+than	O
+their	O
+germyl	O
+and	O
+tert	O
+-	O
+butyl	O
+analogues	O
+.	O
+
+CYTOTOXIC	O
+ACTIVITY	O
+OF	O
+SILYL	O
+-	O
+AND	O
+GERMYL	O
+-	O
+SUBSTITUTED	O
+4	O
+,	O
+4	O
+-	O
+DIOXO	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+DIHYDROTHIENO	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+ISOXAZOLINES	O
+-	O
+2	O
+
+E	O
+.	O
+
+Lukevics	O
+*	O
+,	O
+P	O
+.	O
+
+Arsenyan	O
+,	O
+I	O
+.	O
+
+Shestakova	O
+,	O
+O	O
+.	O
+
+Zharkova	O
+,	O
+I	O
+.	O
+
+Kanepe	O
+,	O
+R	O
+.	O
+
+Mezapuke	O
+,	O
+and	O
+O	O
+.	O
+
+Pudova	O
+Latvian	O
+Institute	O
+of	O
+Organic	O
+Synthesis	O
+,	O
+Aizkraukles	O
+21	O
+,	O
+Riga	O
+,	O
+LV	O
+-	O
+1006	O
+,	O
+Latvia	O
+
+ABSTRACT	O
+The	O
+[	O
+2	O
++	O
+3	O
+]	O
+dipolar	O
+cycloaddition	O
+of	O
+nitrile	O
+oxides	O
+to	O
+the	O
+double	O
+(	O
+3	O
+=	O
+(	O
+3	O
+bonds	O
+of	O
+thiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioides	O
+leads	O
+to	O
+formation	O
+of	O
+the	O
+fused	O
+isoxazolines	O
+-	O
+2	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+Tumor	O
+growth	O
+inhibition	O
+of	O
+these	O
+compounds	O
+strongly	O
+depends	O
+on	O
+the	O
+nature	O
+of	O
+group	O
+IV	O
+A	O
+element	O
+increasing	O
+from	O
+slightly	O
+active	O
+ert	O
+-	O
+butyl	O
+derivatives	O
+to	O
+silicon	O
+and	O
+germanium	O
+containing	O
+analogues	O
+.	O
+
+The	O
+products	O
+of	O
+benzonitdle	O
+oxide	O
+cycloaddition	O
+have	O
+greater	O
+cytotoic	O
+effect	O
+than	O
+the	O
+compounds	O
+obtained	O
+from	O
+he	O
+cycloaddition	O
+reaction	O
+of	O
+2	O
+,	O
+5	O
+-	O
+disubstituted	O
+thiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioxides	O
+with	O
+acetonitrile	O
+oxide	O
+.	O
+
+Fused	O
+silyl	O
+substituted	O
+isoxazolines	O
+-	O
+2	O
+are	O
+stronger	O
+NO	O
+-	O
+inducers	O
+than	O
+their	O
+germyl	O
+and	O
+tert	O
+-	O
+butyl	O
+analogues	O
+.	O
+
+INTRODUCTION	O
+The	O
+interest	O
+in	O
+silyl	O
+substituted	O
+thiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioxides	O
+stems	O
+from	O
+the	O
+fact	O
+that	O
+they	O
+are	O
+useful	O
+synthetic	O
+intermediates	O
+for	O
+the	O
+preparation	O
+of	O
+various	O
+types	O
+of	O
+organic	O
+compounds	O
+by	O
+Diels	O
+-	O
+Alder	O
+cycloaddition	O
+[	O
+1	O
+]	O
+,	O
+amine	O
+induced	O
+ring	O
+-	O
+opening	O
+reaction	O
+[	O
+2	O
+]	O
+,	O
+or	O
+coupling	O
+of	O
+bromothiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioxides	O
+with	O
+thienyl	O
+stannanes	O
+in	O
+the	O
+presence	O
+of	O
+a	O
+palladium	O
+(	O
+0	O
+)	O
+catalyst	O
+[	O
+3	O
+]	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+that	O
+unsubstituted	O
+thiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioxide	O
+prepared	O
+in	O
+situ	O
+is	O
+a	O
+quite	O
+reactive	O
+dipolarophile	O
+in	O
+the	O
+[	O
+2	O
++	O
+3	O
+]	O
+cycloaddition	O
+reactions	O
+with	O
+N	O
+,	O
+o	O
+-	O
+diphenylnitrone	O
+[	O
+4	O
+]	O
+,	O
+benzonitrile	O
+[	O
+4	O
+,	O
+5	O
+]	O
+and	O
+mesitonitrile	O
+[	O
+4	O
+,	O
+5	O
+]	O
+oxides	O
+yielding	O
+mono	O
+-	O
+and	O
+diisoxazolines	O
+-	O
+2	O
+and	O
+N	O
+-	O
+substituted	O
+isoxazolidines	O
+.	O
+
+Moreover	O
+,	O
+our	O
+recent	O
+studies	O
+indicate	O
+that	O
+silyl	O
+-	O
+and	O
+germylcontaining	O
+isoxazolines	O
+have	O
+gained	O
+a	O
+great	O
+deal	O
+of	O
+attention	O
+as	O
+compounds	O
+possessing	O
+a	O
+wide	O
+spectrum	O
+of	O
+the	O
+biological	O
+properties	O
+.	O
+
+The	O
+vasodilating	O
+,	O
+anticoagulant	O
+and	O
+cardioprotective	O
+activity	O
+of	O
+5	O
+-	O
+Si	O
+-	O
+(	O
+Ge	O
+)	O
+substituted	O
+isoxazolines	O
+-	O
+2	O
+has	O
+been	O
+studied	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+[	O
+6	O
+,	O
+7	O
+]	O
+.	O
+
+The	O
+most	O
+active	O
+isoxazoline	O
+-	O
+3	O
+-	O
+(	O
+5	O
+"	O
+-	O
+triethylgermyl	O
+-	O
+3	O
+"	O
+-	O
+isoxazolino	O
+)	O
+pyridine	O
+hydrochloride	O
+protected	O
+the	O
+heart	O
+from	O
+rhythm	O
+disturbances	O
+and	O
+lethality	O
+during	O
+ischemiareperfusion	O
+[	O
+7	O
+]	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+that	O
+silylisoxazolines	O
+-	O
+2	O
+are	O
+more	O
+potent	O
+in	O
+protection	O
+against	O
+hypoxia	O
+and	O
+corazole	O
+convulsions	O
+than	O
+germanium	O
+analogues	O
+.	O
+
+However	O
+,	O
+germylisoxazolines	O
+-	O
+2	O
+are	O
+stronger	O
+tumor	O
+growth	O
+inhibitors	O
+and	O
+NO	O
+-	O
+inducers	O
+than	O
+their	O
+silicon	O
+analogue	O
+[	O
+8	O
+]	O
+.	O
+
+This	O
+work	O
+presents	O
+the	O
+results	O
+of	O
+cytotoxic	O
+activity	O
+for	O
+fused	O
+isoxazolines	O
+-	O
+2	O
+bearing	O
+a	O
+group	O
+14	O
+element	O
+as	O
+substituent	O
+(	O
+1	O
+,	O
+2	O
+)	O
+in	O
+function	O
+of	O
+the	O
+nature	O
+of	O
+the	O
+group	O
+14	O
+element	O
+.	O
+
+M	O
+
+e3M	O
+.	O
+CH3	O
+N	O
+
+-	O
+0	O
+\	O
+R	O
+
+O	O
+\	O
+M	O
+
+e3M	O
+S	O
+
+N	O
+
+02	O
+
+02	O
+2	O
+
+1	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+CHEMISTRY	O
+Seven	O
+tert	O
+-	O
+butyl	O
+-	O
+,	O
+trimethylsilyl	O
+-	O
+,	O
+and	O
+trimethylgermyl	O
+-	O
+substituted	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3a	O
+,	O
+6adihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+1	O
+and	O
+2	O
+(	O
+Table	O
+1	O
+)	O
+were	O
+prepared	O
+by	O
+the	O
+[	O
+2	O
++	O
+3	O
+]	O
+dipolar	O
+63	O
+
+Vol	O
+.	O
+
+7	O
+,	O
+No	O
+.	O
+2	O
+,	O
+2000	O
+
+Cytotoxic	O
+Activity	O
+ofSilyl	O
+-	O
+and	O
+Germyl	O
+-	O
+Substituted	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+Dihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+Isoxazolines	O
+-	O
+2	O
+
+cycloaddition	O
+of	O
+aceto	O
+-	O
+and	O
+benzonitrile	O
+oxides	O
+to	O
+2	O
+,	O
+5	O
+-	O
+disubstituted	O
+thiophene	O
+-	O
+l	O
+,	O
+l	O
+-	O
+dioxides	O
+.	O
+
+Their	O
+synthesis	O
+and	O
+characterization	O
+are	O
+given	O
+in	O
+ref	O
+.	O
+
+[	O
+9	O
+]	O
+.	O
+
+_	O
+,	O
+,	O
+/	O
+0	O
+\	O
+N	O
+Me3M	O
+M	O
+'	O
+Me3	O
+
+Me3M	O
+
+02	O
+M	O
+,	O
+M	O
+'	O
+=	O
+C	O
+,	O
+Si	O
+,	O
+Ge	O
+;	O
+R	O
+=	O
+Me	O
+,	O
+Ph	O
+;	O
+R	O
+'	O
+=	O
+H	O
+,	O
+Me3Ge	O
+Table	O
+1	O
+.	O
+
+Me3C	O
+,	O
+MeSi	O
+,	O
+Investigated	O
+dihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazolines	O
+-	O
+2	O
+
+02	O
+Me3Ge	O
+substituted	O
+
+%	O
+,	O
+\	O
+R	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3a	O
+,	O
+6a	O
+
+Compound	O
+
+'	O
+Type	O
+la	O
+
+M	O
+
+R	O
+H	O
+Me3Ge	O
+Me3Ge	O
+
+Yield	O
+
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3	O
+methyl	O
+"	O
+5	O
+-	O
+tert	O
+-	O
+butyl	O
+-	O
+3a	O
+,	O
+6adihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+
+(	O
+3	O
+'	O
+C	O
+Si	O
+
+(	O
+%	O
+)	O
+80	O
+
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3	O
+-	O
+methyl	O
+-	O
+3a	O
+-	O
+trimethylgermyl	O
+-	O
+5	O
+-	O
+tert	O
+-	O
+butyl3a	O
+,	O
+6a	O
+-	O
+d	O
+ihyd	O
+rothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoli	O
+ne	O
+-	O
+2	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3	O
+-	O
+methyl	O
+-	O
+3a	O
+-	O
+trimethyigermyl	O
+-	O
+5tri	O
+methylsilyl	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+d	O
+hyd	O
+roth	O
+ien	O
+o	O
+[	O
+2	O
+,	O
+3d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+4	O
+,	O
+4	O
+-	O
+d	O
+io	O
+x	O
+o	O
+-	O
+3	O
+-	O
+meth	O
+y	O
+I	O
+-	O
+3a	O
+,	O
+5	O
+-	O
+b	O
+s	O
+tri	O
+m	O
+ethy	O
+Ig	O
+e	O
+rmy	O
+I	O
+)	O
+3a	O
+,	O
+6a	O
+-	O
+d	O
+hyd	O
+rothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazo	O
+ne	O
+-	O
+2	O
+4	O
+,	O
+4	O
+-	O
+d	O
+ioxo	O
+-	O
+3	O
+-	O
+ph	O
+en	O
+y	O
+I	O
+-	O
+5	O
+-	O
+tert	O
+-	O
+b	O
+uty	O
+I	O
+-	O
+3a	O
+,	O
+6adihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+4	O
+,	O
+4	O
+-	O
+d	O
+ioxo	O
+-	O
+3	O
+-	O
+p	O
+h	O
+e	O
+ny	O
+I	O
+-	O
+5	O
+-	O
+tri	O
+meth	O
+y	O
+si	O
+ly	O
+I	O
+-	O
+3a	O
+,	O
+6adihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+4	O
+,	O
+4	O
+-	O
+d	O
+ioxo	O
+-	O
+3	O
+-	O
+p	O
+h	O
+e	O
+n	O
+y	O
+I	O
+-	O
+5	O
+-	O
+tri	O
+methy	O
+Ig	O
+e	O
+rmy	O
+I	O
+-	O
+3a	O
+,	O
+6adi	O
+,	O
+hydr0thieno	O
+[	O
+2	O
+,	O
+3	O
+,	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+
+lb	O
+lc	O
+
+58	O
+45	O
+67	O
+84	O
+
+ld	O
+2a	O
+2b	O
+
+Ge	O
+
+Me3Ge	O
+
+C	O
+Si	O
+
+77	O
+85	O
+
+2c	O
+
+Ge	O
+
+IN	O
+VITRO	O
+CYTOTOXITY	O
+ASSAY	O
+Monolayer	O
+cells	O
+lines	O
+were	O
+cultivated	O
+for	O
+72	O
+h	O
+in	O
+DMEM	O
+standard	O
+medium	O
+without	O
+an	O
+indicator	O
+and	O
+antibiotics	O
+.	O
+
+After	O
+the	O
+ampoule	O
+was	O
+defreezed	O
+not	O
+more	O
+than	O
+four	O
+passa4ges	O
+were	O
+performed	O
+.	O
+
+The	O
+control	O
+cells	O
+and	O
+cells	O
+with	O
+tested	O
+substances	O
+in	O
+the	O
+range	O
+of	O
+2	O
+-	O
+5	O
+10	O
+cell	O
+/	O
+mL	O
+concentration	O
+(	O
+depending	O
+on	O
+line	O
+nature	O
+)	O
+were	O
+placed	O
+on	O
+a	O
+separate	O
+96	O
+wells	O
+plates	O
+.	O
+
+Solutions	O
+containing	O
+test	O
+compounds	O
+were	O
+diluted	O
+and	O
+added	O
+in	O
+wells	O
+to	O
+give	O
+the	O
+final	O
+concentrations	O
+of	O
+50	O
+,	O
+25	O
+,	O
+12	O
+.	O
+5	O
+,	O
+and	O
+6	O
+.	O
+25	O
+#	O
+g	O
+/	O
+mL	O
+Control	O
+cells	O
+were	O
+treated	O
+in	O
+the	O
+same	O
+manner	O
+only	O
+in	O
+the	O
+absence	O
+of	O
+test	O
+compounds	O
+.	O
+
+Plates	O
+were	O
+cultivated	O
+for	O
+72	O
+h	O
+.	O
+
+A	O
+quantity	O
+of	O
+survived	O
+cells	O
+was	O
+determined	O
+using	O
+crystal	O
+violet	O
+(	O
+CV	O
+)	O
+or	O
+3	O
+-	O
+(	O
+4	O
+,	O
+5	O
+-	O
+dimethylthiazol	O
+-	O
+2	O
+-	O
+yl	O
+)	O
+-	O
+2	O
+,	O
+5diphenyltetrazolini	O
+bromide	O
+(	O
+MTT	O
+)	O
+coloration	O
+which	O
+was	O
+assayed	O
+by	O
+multiscan	O
+spectrofotometer	O
+.	O
+
+The	O
+quantity	O
+of	O
+alive	O
+cells	O
+on	O
+control	O
+plate	O
+was	O
+taken	O
+in	O
+calculations	O
+for	O
+100	O
+%	O
+[	O
+10	O
+,	O
+11	O
+]	O
+.	O
+
+Concentration	O
+of	O
+NO	O
+was	O
+determined	O
+according	O
+to	O
+[	O
+10	O
+]	O
+.	O
+
+RESULTS	O
+AND	O
+DISCUSSION	O
+Potential	O
+cytotoxic	O
+activity	O
+of	O
+synthesized	O
+fused	O
+isoxazolines	O
+1	O
+and	O
+2	O
+was	O
+tested	O
+in	O
+vitro	O
+on	O
+four	O
+monolayer	O
+tumor	O
+cell	O
+lines	O
+:	O
+MG	O
+-	O
+22A	O
+(	O
+mouse	B
+hepatoma	O
+)	O
+,	O
+HT	O
+-	O
+1080	O
+(	O
+human	B
+fibroblastoma	O
+)	O
+,	O
+B16	O
+(	O
+mouse	B
+melanoma	O
+)	O
+,	O
+Neuro	O
+2A	O
+(	O
+mouse	B
+neiroblastoma	O
+)	O
+.	O
+
+Concentrations	O
+providing	O
+50	O
+%	O
+of	O
+tumor	O
+death	O
+effect	O
+were	O
+determined	O
+according	O
+to	O
+the	O
+known	O
+procedure	O
+[	O
+12	O
+]	O
+using	O
+96	O
+well	O
+plates	O
+.	O
+
+The	O
+experimental	O
+evaluation	O
+of	O
+cytotoxicity	O
+properties	O
+is	O
+presented	O
+in	O
+Table	O
+2	O
+.	O
+
+A	O
+preliminary	O
+analysis	O
+of	O
+the	O
+structure	O
+-	O
+activity	O
+relationship	O
+for	O
+the	O
+cytotoxic	O
+action	O
+clearly	O
+indicates	O
+the	O
+strong	O
+influence	O
+of	O
+the	O
+MeM	O
+(	O
+M	O
+=	O
+C	O
+,	O
+Si	O
+,	O
+Ge	O
+)	O
+group	O
+in	O
+position	O
+5	O
+of	O
+fused	O
+isoxazolines	O
+1	O
+and	O
+2	O
+.	O
+
+Derivatives	O
+bearing	O
+tert	O
+-	O
+butyl	O
+substituent	O
+(	O
+la	O
+,	O
+b	O
+and	O
+2a	O
+)	O
+have	O
+a	O
+slight	O
+cytotoxic	O
+effect	O
+(	O
+>	O
+10	O
+#	O
+g	O
+/	O
+mL	O
+)	O
+.	O
+
+The	O
+substitution	O
+of	O
+the	O
+tert	O
+-	O
+butyl	O
+group	O
+by	O
+trimethylsilyl	O
+or	O
+64	O
+
+E	O
+.	O
+
+Lukevics	O
+et	O
+al	O
+.	O
+
+Metal	O
+-	O
+Based	O
+Drugs	O
+
+A	O
+
+oO	O
+
+{	O
+D	O
+
+0	O
+
+0	O
+
+65	O
+
+Vol	O
+.	O
+
+7	O
+,	O
+No	O
+.	O
+2	O
+,	O
+2000	O
+
+Cytotoxic	O
+Activity	O
+ofSilyl	O
+-	O
+and	O
+Germyl	O
+-	O
+Substituted	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+Dihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+Isoxazolines	O
+-	O
+2	O
+
+trimethylgermyl	O
+ones	O
+leads	O
+to	O
+considerable	O
+increase	O
+of	O
+cytotoxicity	O
+.	O
+
+It	O
+must	O
+be	O
+noted	O
+that	O
+the	O
+activity	O
+of	O
+silicon	O
+-	O
+and	O
+germanium	O
+-	O
+containing	O
+compounds	O
+(	O
+1	O
+and	O
+l	O
+d	O
+)	O
+depends	O
+on	O
+the	O
+tumor	O
+type	O
+.	O
+
+5	O
+-	O
+Trimethylsilyl	O
+-	O
+substituted	O
+fused	O
+isoxazoline	O
+le	O
+is	O
+more	O
+active	O
+than	O
+the	O
+germanium	O
+analogue	O
+l	O
+d	O
+in	O
+tests	O
+on	O
+HP	O
+-	O
+1080	O
+and	O
+MG	O
+-	O
+22A	O
+cell	O
+lines	O
+.	O
+
+However	O
+,	O
+the	O
+germanium	O
+compound	O
+ld	O
+has	O
+greater	O
+cytotoxic	O
+effect	O
+on	O
+Neuro	O
+2A	O
+and	O
+B16	O
+cell	O
+lines	O
+than	O
+the	O
+silicon	O
+derivative	O
+lc	O
+.	O
+
+Comparison	O
+of	O
+the	O
+tumor	O
+growth	O
+inhibition	O
+for	O
+derivatives	O
+1	O
+and	O
+2	O
+shows	O
+a	O
+higher	O
+activity	O
+of	O
+the	O
+condensed	O
+isoxazolines	O
+2	O
+containing	O
+a	O
+phenyl	O
+group	O
+in	O
+position	O
+3	O
+with	O
+respect	O
+to	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3	O
+-	O
+methyl	O
+-	O
+3a	O
+-	O
+trimethylgermyl	O
+-	O
+5	O
+-	O
+MeM	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+dihyd	O
+rothieno	O
+[	O
+2	O
+,	O
+3d	O
+]	O
+isoxazolines	O
+l	O
+b	O
+-	O
+d	O
+.	O
+
+Silyl	O
+-	O
+and	O
+germyl	O
+-	O
+substituted	O
+fused	O
+isoxazolines	O
+have	O
+a	O
+medium	O
+NOinduction	O
+ability	O
+,	O
+4	O
+,	O
+4	O
+-	O
+dioxo	O
+-	O
+3	O
+-	O
+phenyl	O
+-	O
+5	O
+-	O
+trimethylsilyl	O
+-	O
+3a	O
+,	O
+6a	O
+-	O
+dihydrothieno	O
+[	O
+2	O
+,	O
+3	O
+-	O
+d	O
+]	O
+isoxazoline	O
+-	O
+2	O
+(	O
+2b	O
+)	O
+being	O
+the	O
+most	O
+active	O
+(	O
+250	O
+%	O
+in	O
+the	O
+MG	O
+-	O
+22A	O
+test	O
+)	O
+.	O
+
+ACKNOWLEGMENT	O
+We	O
+are	O
+grateful	O
+to	O
+Latvian	O
+Taiho	O
+Foundation	O
+for	O
+financial	O
+support	O
+.	O
+
+REFERENCES	O
+1	O
+.	O
+
+A	O
+.	O
+
+R	O
+.	O
+
+M	O
+.	O
+
+Donovan	O
+,	O
+M	O
+.	O
+
+K	O
+.	O
+
+Shepherd	O
+,	O
+Tetrahedron	O
+Lett	O
+.	O
+,	O
+35	O
+(	O
+1994	O
+)	O
+4425	O
+.	O
+
+2	O
+.	O
+
+S	O
+.	O
+
+Gronowitz	O
+,	O
+A	O
+.	O
+-	O
+B	O
+.	O
+
+H0rnfeldt	O
+,	O
+E	O
+.	O
+
+Lukevics	O
+,	O
+O	O
+.	O
+
+Pudova	O
+,	O
+Synthesis	O
+,	O
+(	O
+1994	O
+)	O
+40	O
+.	O
+
+3	O
+.	O
+
+G	O
+.	O
+
+Barbarella	O
+,	O
+L	O
+.	O
+
+Favaretto	O
+,	O
+G	O
+.	O
+
+Sotgiu	O
+,	O
+M	O
+.	O
+
+Zambianchi	O
+,	O
+L	O
+.	O
+
+Antolini	O
+,	O
+O	O
+.	O
+
+Pudova	O
+,	O
+A	O
+.	O
+
+Bongini	O
+,	O
+J	O
+.	O
+
+Org	O
+.	O
+
+Chem	O
+.	O
+,	O
+63	O
+(	O
+1998	O
+)	O
+5497	O
+.	O
+
+4	O
+.	O
+
+A	O
+.	O
+
+Bened	O
+,	O
+R	O
+.	O
+
+Durand	O
+,	O
+D	O
+.	O
+
+Pioch	O
+,	O
+P	O
+.	O
+
+Geneste	O
+,	O
+J	O
+.	O
+
+P	O
+.	O
+
+Declerq	O
+,	O
+G	O
+.	O
+
+Germain	O
+,	O
+J	O
+.	O
+
+Rambaud	O
+,	O
+R	O
+.	O
+
+Roques	O
+,	O
+J	O
+.	O
+
+Org	O
+.	O
+
+Chem	O
+.	O
+,	O
+46	O
+(	O
+1981	O
+)	O
+3502	O
+.	O
+
+5	O
+.	O
+
+F	O
+.	O
+
+M	O
+.	O
+
+Albini	O
+,	O
+P	O
+.	O
+
+Ceva	O
+,	O
+A	O
+.	O
+
+Mascherpa	O
+,	O
+E	O
+.	O
+
+Albini	O
+,	O
+P	O
+.	O
+
+Caramella	O
+,	O
+Tetrahedron	O
+,	O
+38	O
+(	O
+1982	O
+)	O
+
+6	O
+.	O
+
+7	O
+.	O
+
+8	O
+.	O
+
+9	O
+.	O
+
+10	O
+.	O
+
+11	O
+.	O
+
+12	O
+.	O
+
+3629	O
+.	O
+
+E	O
+.	O
+
+Lukevics	O
+,	O
+M	O
+.	O
+
+Veveris	O
+,	O
+V	O
+.	O
+
+Dirnens	O
+,	O
+Appl	O
+.	O
+
+Organomet	O
+.	O
+
+Chem	O
+.	O
+,	O
+11	O
+(	O
+1997	O
+)	O
+805	O
+.	O
+
+E	O
+.	O
+
+Lukevics	O
+,	O
+P	O
+.	O
+
+Arsenyan	O
+,	O
+M	O
+.	O
+
+Veveris	O
+,	O
+Metal	O
+Based	O
+Drugs	O
+,	O
+5	O
+(	O
+1998	O
+)	O
+251	O
+.	O
+
+E	O
+.	O
+
+Lukevics	O
+,	O
+P	O
+.	O
+
+Arsenyan	O
+,	O
+S	O
+.	O
+
+Germane	O
+,	O
+I	O
+.	O
+
+Shestakova	O
+,	O
+Applied	O
+Organomet	O
+.	O
+
+Chem	O
+.	O
+,	O
+13	O
+(	O
+1999	O
+)	O
+795	O
+.	O
+
+E	O
+.	O
+
+Lukevics	O
+,	O
+P	O
+.	O
+
+Arsenyan	O
+,	O
+S	O
+.	O
+
+Belyakov	O
+,	O
+J	O
+.	O
+
+Popelis	O
+,	O
+O	O
+.	O
+
+Pudova	O
+,	O
+Organometallics	O
+,	O
+18	O
+(	O
+1999	O
+)	O
+3187	O
+.	O
+
+D	O
+.	O
+J	O
+.	O
+
+Fast	O
+,	O
+R	O
+.	O
+C	O
+.	O
+
+Lynch	O
+,	O
+R	O
+.	O
+W	O
+.	O
+
+Leu	O
+,	O
+J	O
+.	O
+
+Leuckocyt	O
+.	O
+
+Biol	O
+.	O
+,	O
+52	O
+(	O
+1992	O
+)	O
+255	O
+.	O
+
+P	O
+.	O
+J	O
+.	O
+
+Freshney	O
+,	O
+Culture	O
+of	O
+Animal	O
+Cells	O
+(	O
+A	O
+Manual	O
+of	O
+Basic	O
+Technique	O
+)	O
+,	O
+Wiley	O
+-	O
+Liss	O
+,	O
+New	O
+York	O
+,	O
+1994	O
+,	O
+pp	O
+.	O
+
+296	O
+-	O
+297	O
+.	O
+
+R	O
+.	O
+
+J	O
+.	O
+
+Riddell	O
+,	O
+R	O
+.	O
+
+H	O
+.	O
+
+Clothier	O
+,	O
+M	O
+.	O
+
+Fd	O
+.	O
+
+Balls	O
+,	O
+Chem	O
+.	O
+
+Toxicol	O
+.	O
+,	O
+24	O
+(	O
+1986	O
+)	O
+469	O
+.	O
+
+Received	O
+:	O
+January	O
+21	O
+,	O
+2000	O
+Accepted	O
+:	O
+February	O
+1	O
+,	O
+2000	O
+Received	O
+in	O
+revised	O
+camera	O
+-	O
+ready	O
+format	O
+"	O
+February	O
+2	O
+,	O
+2000	O
+
+66	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+from	O
+bone	O
+marrow	O
+to	O
+blood	O
+and	O
+tissues	O
+in	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+visceral	O
+larva	O
+migrans	O
+syndrome	O
+
+Abstract	O
+
+This	O
+study	O
+was	O
+undertaken	O
+to	O
+evaluate	O
+the	O
+role	O
+of	O
+IL	O
+-	O
+5	O
+in	O
+eosinophil	O
+migration	O
+and	O
+in	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+in	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+visceral	O
+larva	O
+migrans	O
+syndrome	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+the	O
+infection	O
+of	O
+animals	O
+with	O
+Toxocara	B
+canis	I
+induced	O
+an	O
+early	O
+increase	O
+in	O
+serum	O
+IL	O
+-	O
+5	O
+levels	O
+that	O
+might	O
+be	O
+essential	O
+for	O
+eosinophil	O
+differentiation	O
+and	O
+proliferation	O
+and	O
+for	O
+the	O
+development	O
+of	O
+eosinophilia	O
+.	O
+
+When	O
+infected	O
+guinea	B
+-	I
+pigs	I
+were	O
+treated	O
+with	O
+mAb	O
+anti	O
+-	O
+IL	O
+-	O
+5	O
+(	O
+TRFK	O
+-	O
+5	O
+)	O
+given	O
+at	O
+the	O
+same	O
+time	O
+or	O
+1	O
+or	O
+3	O
+days	O
+after	O
+infection	O
+,	O
+there	O
+was	O
+a	O
+high	O
+percentage	O
+of	O
+reduction	O
+of	O
+eosinophil	O
+counts	O
+18	O
+days	O
+after	O
+infection	O
+.	O
+
+However	O
+,	O
+when	O
+the	O
+mAb	O
+was	O
+administered	O
+during	O
+the	O
+peak	O
+of	O
+eosinophilia	O
+,	O
+there	O
+was	O
+high	O
+inhibition	O
+in	O
+blood	O
+,	O
+no	O
+inhibition	O
+in	O
+bronchoalveolar	O
+lavage	O
+fluid	O
+(	O
+BALF	O
+)	O
+or	O
+peritoneum	O
+and	O
+an	O
+increase	O
+in	O
+eosinophil	O
+numbers	O
+in	O
+bone	O
+marrow	O
+.	O
+
+Thus	O
+,	O
+a	O
+basic	O
+level	O
+of	O
+IL	O
+-	O
+5	O
+may	O
+be	O
+essential	O
+to	O
+drive	O
+eosinophils	O
+from	O
+bone	O
+marrow	O
+to	O
+blood	O
+and	O
+tissues	O
+,	O
+and	O
+for	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+in	O
+infected	O
+animals	O
+.	O
+
+We	O
+may	O
+also	O
+conclude	O
+that	O
+when	O
+eosinophils	O
+have	O
+already	O
+migrated	O
+to	O
+the	O
+lungs	O
+,	O
+TRFK	O
+-	O
+5	O
+has	O
+no	O
+power	O
+to	O
+inhibit	O
+eosinophilia	O
+,	O
+which	O
+is	O
+also	O
+under	O
+control	O
+of	O
+local	O
+lung	O
+cells	O
+producing	O
+IL	O
+-	O
+5	O
+.	O
+
+In	O
+this	O
+way	O
+,	O
+only	O
+one	O
+later	O
+TRFK	O
+-	O
+5	O
+treatment	O
+may	O
+not	O
+be	O
+sufficient	O
+to	O
+modify	O
+the	O
+lung	O
+parenchyma	O
+microenvironment	O
+,	O
+since	O
+T	B
+.	I
+canis	I
+antigens	O
+had	O
+already	O
+stimulated	O
+some	O
+cell	O
+populations	O
+to	O
+produce	O
+IL	O
+-	O
+5	O
+.	O
+
+Research	O
+Paper	O
+Mediators	O
+of	O
+Inflammation	O
+5	O
+,	O
+24	O
+-	O
+31	O
+(	O
+1996	O
+)	O
+
+Tins	O
+study	O
+was	O
+undertaken	O
+to	O
+evaluate	O
+the	O
+role	O
+of	O
+11	O
+-	O
+5	O
+in	O
+eosinophil	O
+migration	O
+and	O
+in	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+in	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+visceral	O
+larva	O
+migrans	O
+syndrome	O
+.	O
+
+The	O
+results	O
+show	O
+that	O
+the	O
+infection	O
+of	O
+animals	O
+with	O
+Toxocara	B
+canis	I
+induced	O
+an	O
+early	O
+increase	O
+in	O
+serum	O
+11	O
+-	O
+5	O
+levels	O
+that	O
+might	O
+be	O
+essential	O
+for	O
+eosi	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+from	O
+bone	O
+marrow	O
+to	O
+blood	O
+and	O
+tissues	O
+in	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+visceral	O
+larva	O
+migrans	O
+syndrome	O
+L	O
+.	O
+
+H	O
+.	O
+
+Faccioli	O
+,	O
+1	O
+"	O
+cA	O
+V	O
+.	O
+
+F	O
+.	O
+
+Mokwa	O
+,	O
+C	O
+.	O
+
+L	O
+.	O
+
+Silva	O
+,	O
+G	O
+.	O
+
+M	O
+.	O
+
+Rocha	O
+,	O
+J	O
+.	O
+
+I	O
+.	O
+
+Araujo	O
+,	O
+M	O
+.	O
+
+A	O
+.	O
+
+Nahori	O
+2	O
+and	O
+B	O
+.	O
+
+B	O
+.	O
+
+Vargaftig	O
+2	O
+
+nophil	O
+differentiation	O
+and	O
+proliferation	O
+and	O
+for	O
+the	O
+development	O
+of	O
+eosinophilia	O
+.	O
+
+When	O
+infected	O
+guinea	B
+-	I
+pigs	I
+were	O
+treated	O
+with	O
+mAb	O
+anti	O
+-	O
+11	O
+-	O
+5	O
+(	O
+TRFK	O
+-	O
+5	O
+)	O
+given	O
+at	O
+the	O
+same	O
+time	O
+or	O
+1	O
+or	O
+3	O
+days	O
+after	O
+infection	O
+,	O
+there	O
+was	O
+a	O
+high	O
+percentage	O
+of	O
+reduction	O
+of	O
+eosinophil	O
+counts	O
+18	O
+days	O
+after	O
+infection	O
+.	O
+
+However	O
+,	O
+when	O
+the	O
+mAb	O
+was	O
+administered	O
+during	O
+the	O
+peak	O
+of	O
+eosinophilia	O
+,	O
+there	O
+was	O
+high	O
+inhibition	O
+in	O
+blood	O
+,	O
+no	O
+inhibition	O
+in	O
+bronchoalveolar	O
+lavage	O
+fluid	O
+(	O
+BALF	O
+)	O
+or	O
+peritoneum	O
+and	O
+an	O
+increase	O
+in	O
+eosinophil	O
+numbers	O
+in	O
+bone	O
+marrow	O
+.	O
+
+Thus	O
+,	O
+a	O
+basic	O
+level	O
+of	O
+11	O
+-	O
+5	O
+may	O
+be	O
+essential	O
+to	O
+drive	O
+eosinophils	O
+from	O
+bone	O
+marrow	O
+to	O
+blood	O
+and	O
+tissues	O
+,	O
+and	O
+for	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+in	O
+infected	O
+animals	O
+.	O
+
+We	O
+may	O
+also	O
+conclude	O
+that	O
+when	O
+eosinophils	O
+have	O
+already	O
+migrated	O
+to	O
+the	O
+lungs	O
+,	O
+TRFK	O
+-	O
+5	O
+has	O
+no	O
+power	O
+to	O
+inhibit	O
+eosinophilia	O
+,	O
+which	O
+is	O
+also	O
+under	O
+control	O
+of	O
+local	O
+lung	O
+cells	O
+producing	O
+11	O
+-	O
+5	O
+.	O
+
+In	O
+this	O
+way	O
+,	O
+only	O
+one	O
+later	O
+TRFK	O
+-	O
+5	O
+treatment	O
+may	O
+not	O
+be	O
+sufficient	O
+to	O
+modify	O
+the	O
+lung	O
+parenchyma	O
+microenvironment	O
+,	O
+since	O
+T	B
+.	I
+canis	I
+antigens	O
+had	O
+already	O
+stimulated	O
+some	O
+cell	O
+populations	O
+to	O
+produce	O
+11	O
+-	O
+5	O
+.	O
+
+1Department	O
+of	O
+Parasitology	O
+,	O
+Microbiology	O
+and	O
+Immunology	O
+,	O
+School	O
+of	O
+Medicine	O
+of	O
+Ribeir	O
+,	O
+5o	O
+Preto	O
+,	O
+14049	O
+-	O
+900	O
+,	O
+Ribeiro	O
+Preto	O
+,	O
+SP	O
+,	O
+Brazil	O
+.	O
+
+Fax	O
+:	O
+(	O
++	O
+55	O
+)	O
+16	O
+633	O
+6631	O
+2Unit	O
+de	O
+Pharmacologie	O
+Cellulaire	O
+,	O
+Unit	O
+Associe	O
+Institut	O
+Pasteur	O
+/	O
+INSERM	O
+n	O
+.	O
+
+285	O
+,	O
+Paris	O
+,	O
+
+France	O
+.	O
+
+CACorresponding	O
+Author	O
+
+Key	O
+words	O
+:	O
+Eosinophil	O
+,	O
+Eosinophilia	O
+by	O
+Toxocara	B
+canis	I
+,	O
+IL	O
+-	O
+5	O
+in	O
+eosinophilia	O
+,	O
+Toxocara	B
+canis	I
+
+Introduction	O
+
+treatment	O
+in	O
+mice	B
+infected	O
+with	O
+
+Eosinophilia	O
+has	O
+been	O
+associated	O
+with	O
+parasitic	O
+diseases	O
+,	O
+particularly	O
+when	O
+the	O
+parasites	O
+invade	O
+the	O
+tissues	O
+or	O
+injure	O
+the	O
+mucosal	O
+surfaces	O
+.	O
+
+Toxocara	B
+canis	I
+is	O
+an	O
+intestinal	O
+parasite	O
+of	O
+dogs	B
+,	O
+and	O
+is	O
+the	O
+most	O
+common	O
+aetiologic	O
+agent	O
+of	O
+visceral	O
+larva	O
+migrans	O
+syndrome	O
+(	O
+VLMS	O
+)	O
+.	O
+
+In	O
+humans	B
+,	O
+VLMS	O
+results	O
+from	O
+the	O
+ingestion	O
+of	O
+embryonated	O
+eggs	O
+of	O
+T	B
+.	I
+canis	I
+,	O
+that	O
+eclode	O
+in	O
+the	O
+small	O
+intesfine	O
+.	O
+
+The	O
+infective	O
+larvae	O
+invade	O
+the	O
+mucosa	O
+,	O
+move	O
+into	O
+the	O
+liver	O
+via	O
+the	O
+portal	O
+circulation	O
+,	O
+and	O
+from	O
+there	O
+to	O
+the	O
+lungs	O
+.	O
+
+2	O
+Beaver	O
+et	O
+al	O
+.	O
+,	O
+3	O
+who	O
+were	O
+the	O
+first	O
+to	O
+describe	O
+this	O
+syndrome	O
+,	O
+noted	O
+the	O
+intense	O
+eosinophilia	O
+which	O
+reaches	O
+more	O
+than	O
+90	O
+%	O
+of	O
+total	O
+leucocyte	O
+counts	O
+.	O
+
+However	O
+,	O
+there	O
+are	O
+few	O
+studies	O
+regarding	O
+the	O
+mechanisms	O
+involved	O
+in	O
+the	O
+blood	O
+and	O
+tissue	O
+eosinophilia	O
+obseeeed	O
+in	O
+VLMS	O
+.	O
+
+Several	O
+investigators	O
+have	O
+suggested	O
+a	O
+direct	O
+correlation	O
+between	O
+eosinophilia	O
+and	O
+interleukin5	O
+(	O
+IL	O
+-	O
+5	O
+)	O
+in	O
+human	B
+helminth	O
+infections4	O
+'	O
+5	O
+and	O
+in	O
+experimental	O
+animal	O
+models	O
+.	O
+
+67	O
+Inhibition	O
+of	O
+eosinophilia	O
+has	O
+been	O
+demonstrated	O
+by	O
+anti	O
+-	O
+IL	O
+-	O
+5	O
+24	O
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+brasiliensis	O
+,	O
+8	O
+$	O
+chistosoma	O
+mansoni	O
+,	O
+Toxocara	B
+canis7	I
+and	O
+Heligmosomoidespolyg	B
+.	O
+
+1	O
+IL	O
+-	O
+5	O
+has	O
+also	O
+been	O
+shown	O
+to	O
+support	O
+the	O
+terminal	O
+differentiation	O
+,	O
+proliferation	O
+of	O
+eosinophil	O
+precursors	O
+11	O
+'	O
+12	O
+and	O
+eosinophil	O
+activation	O
+.	O
+
+13	O
+Although	O
+IL	O
+-	O
+5	O
+does	O
+not	O
+demonstrate	O
+eosinophil	O
+chemotactic	O
+activity	O
+in	O
+vivo14	O
+there	O
+is	O
+some	O
+evidence	O
+suggesting	O
+that	O
+this	O
+cytokine	O
+may	O
+modulate	O
+a	O
+selective	O
+eosinophil	O
+accumulation	O
+at	O
+the	O
+site	O
+of	O
+inflammation	O
+.	O
+
+Moreover	O
+,	O
+Sehmi	O
+et	O
+a	O
+/	O
+.	O
+15	O
+reported	O
+that	O
+IL	O
+-	O
+5	O
+has	O
+a	O
+selective	O
+priming	O
+effect	O
+on	O
+eosinophil	O
+migratory	O
+response	O
+to	O
+nonselective	O
+chemoattractant	O
+mediators	O
+in	O
+vitro	O
+.	O
+
+Also	O
+,	O
+Moser	O
+et	O
+a	O
+/	O
+.	O
+
+16	O
+have	O
+demonstrated	O
+that	O
+in	O
+order	O
+to	O
+acquire	O
+the	O
+ability	O
+to	O
+transmigrate	O
+,	O
+eosinophils	O
+must	O
+be	O
+primed	O
+with	O
+IL	O
+-	O
+5	O
+,	O
+IL	O
+-	O
+3	O
+and	O
+GM	O
+-	O
+CSF	O
+.	O
+
+Thus	O
+,	O
+the	O
+involvement	O
+of	O
+IL	O
+-	O
+5	O
+in	O
+eosinophilia	O
+is	O
+not	O
+fully	O
+understood	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+we	O
+have	O
+used	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+VLMS	O
+to	O
+investigate	O
+the	O
+involvement	O
+of	O
+IL	O
+-	O
+5	O
+in	O
+eosinophil	O
+migration	O
+and	O
+in	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+in	O
+blood	O
+,	O
+bone	O
+marrow	O
+,	O
+lung	O
+and	O
+peritoneal	O
+cavity	O
+.	O
+
+(	O
+C	O
+)	O
+1996	O
+Rapid	O
+Science	O
+Publishers	O
+
+Nipostrongylus	O
+
+1996	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+in	O
+guinea	B
+-	I
+pig	I
+
+Materials	O
+and	O
+Methods	O
+Animals	O
+:	O
+Outbred	O
+albino	O
+weighing	O
+300	O
+-	O
+400g	O
+at	O
+the	O
+ments	O
+were	O
+obtained	O
+from	O
+the	O
+School	O
+of	O
+Medicine	O
+of	O
+versity	O
+of	O
+So	O
+Paulo	O
+,	O
+Brazil	O
+.	O
+
+female	O
+guinea	B
+-	I
+pigs	I
+start	O
+of	O
+the	O
+experi	O
+
+were	O
+routinely	O
+processed	O
+,	O
+embedded	O
+in	O
+paraffin	O
+,	O
+sectioned	O
+at	O
+4	O
+-	O
+61	O
+.	O
+tm	O
+,	O
+and	O
+stained	O
+with	O
+Chromothope	O
+2R	O
+and	O
+haematoxylin	O
+,	O
+for	O
+examination	O
+by	O
+light	O
+microscopy	O
+.	O
+
+Determination	O
+oflL	O
+-	O
+5	O
+in	O
+serum	O
+:	O
+The	O
+IL	O
+-	O
+5	O
+level	O
+in	O
+the	O
+serum	O
+of	O
+guinea	B
+-	I
+pigs	I
+was	O
+measured	O
+using	O
+an	O
+enzyme	O
+-	O
+linked	O
+immunosorbent	O
+assay	O
+(	O
+ELISA	O
+)	O
+.	O
+
+Briefly	O
+,	O
+ELISA	O
+plates	O
+(	O
+96	O
+-	O
+well	O
+Immunoplate	O
+MaxiSorp	O
+,	O
+Nunc	O
+,	O
+Roskilde	O
+,	O
+Denmark	O
+)	O
+were	O
+coated	O
+with	O
+IL	O
+-	O
+5	O
+-	O
+specific	O
+monoclonal	O
+antibody	O
+(	O
+TRFK	O
+-	O
+5	O
+,	O
+5	O
+lag	O
+/	O
+ml	O
+in	O
+phosphate	O
+buffered	O
+saline	O
+,	O
+pH	O
+7	O
+.	O
+4	O
+,	O
+PBS	O
+,	O
+100	O
+l	O
+.	O
+tl	O
+/	O
+well	O
+)	O
+.	O
+
+After	O
+2	O
+h	O
+of	O
+incubation	O
+at	O
+37C	O
+,	O
+the	O
+wells	O
+were	O
+washed	O
+four	O
+times	O
+with	O
+PBS	O
+containing	O
+0	O
+.	O
+1	O
+%	O
+Tween	O
+20	O
+(	O
+PBS	O
+-	O
+T	O
+)	O
+.	O
+
+Then	O
+,	O
+100	O
+btl	O
+of	O
+samples	O
+or	O
+recombinant	O
+murine	B
+IL	O
+-	O
+5	O
+standards	O
+(	O
+0	O
+.	O
+15	O
+-	O
+200ng	O
+/	O
+ml	O
+)	O
+in	O
+PBS	O
+-	O
+T	O
+and	O
+2	O
+%	O
+BSA	O
+(	O
+PBSTBSA	O
+)	O
+were	O
+added	O
+to	O
+each	O
+well	O
+.	O
+
+After	O
+incubation	O
+for	O
+l	O
+h	O
+at	O
+37C	O
+,	O
+the	O
+wells	O
+were	O
+washed	O
+three	O
+times	O
+and	O
+100	O
+l	O
+.	O
+tl	O
+of	O
+biotinylated	O
+rat	B
+anti	O
+-	O
+murine	B
+IL	O
+-	O
+5	O
+(	O
+biotinylated	O
+-	O
+TRFK	O
+-	O
+5	O
+,	O
+1	O
+lag	O
+/	O
+ml	O
+in	O
+PBS	O
+-	O
+TBSA	O
+)	O
+was	O
+added	O
+.	O
+
+After	O
+incubation	O
+for	O
+1	O
+h	O
+at	O
+37C	O
+,	O
+the	O
+wells	O
+were	O
+washed	O
+again	O
+three	O
+times	O
+and	O
+100	O
+of	O
+peroxidase	O
+-	O
+labelled	O
+streptavidin	O
+(	O
+1	O
+/	O
+1000	O
+,	O
+Kirkegaard	O
+&	O
+Perry	O
+Laboratories	O
+Inc	O
+.	O
+,	O
+Maryland	O
+,	O
+USA	O
+)	O
+were	O
+added	O
+to	O
+each	O
+well	O
+.	O
+
+Following	O
+incubation	O
+for	O
+l	O
+h	O
+at	O
+37C	O
+and	O
+further	O
+washing	O
+,	O
+the	O
+enzyme	O
+was	O
+developed	O
+using	O
+the	O
+TMB	O
+substrate	O
+peroxidase	O
+for	O
+5	O
+min	O
+.	O
+
+The	O
+reaction	O
+was	O
+stopped	O
+by	O
+adding	O
+501	O
+.	O
+tl	O
+of	O
+2	O
+.	O
+0	O
+N	O
+HCl	O
+,	O
+and	O
+the	O
+optical	O
+densities	O
+were	O
+read	O
+at	O
+490nm	O
+using	O
+an	O
+automated	O
+plate	O
+reader	O
+.	O
+
+The	O
+sensitivity	O
+of	O
+the	O
+assay	O
+was	O
+0	O
+.	O
+15	O
+ng	O
+/	O
+ml	O
+and	O
+the	O
+upper	O
+limit	O
+100ng	O
+/	O
+ml	O
+.	O
+
+the	O
+animal	O
+house	O
+of	O
+Ribeiro	O
+Preto	O
+,	O
+Uni	O
+
+Infection	O
+of	O
+animals	O
+:	O
+T	B
+.	I
+canis	I
+eggs	O
+were	O
+obtained	O
+by	O
+the	O
+methods	O
+of	O
+Olson	O
+and	O
+Schulz	O
+,	O
+17	O
+with	O
+minor	O
+modifications	O
+.	O
+
+Briefly	O
+,	O
+gravid	O
+female	O
+worms	O
+were	O
+recovered	O
+from	O
+dogs	B
+,	O
+and	O
+the	O
+eggs	O
+were	O
+rescued	O
+from	O
+the	O
+uterus	O
+,	O
+washed	O
+and	O
+allowed	O
+to	O
+develop	O
+to	O
+the	O
+infective	O
+stage	O
+in	O
+shallow	O
+dishes	O
+containing	O
+0	O
+.	O
+5	O
+%	O
+formalin	O
+at	O
+37C	O
+.	O
+
+Under	O
+light	O
+ether	O
+anaesthesia	O
+,	O
+the	O
+animals	O
+were	O
+infected	O
+with	O
+I	O
+ml	O
+saline	O
+containing	O
+500	O
+T	B
+.	I
+canis	I
+eggs	O
+,	O
+by	O
+gastric	O
+intubation	O
+using	O
+a	O
+metal	O
+cannula	O
+.	O
+
+Blood	O
+cell	O
+counts	O
+:	O
+Guinea	B
+-	I
+pigs	I
+were	O
+anaesthetized	O
+with	O
+sodium	O
+pentobarbitone	O
+(	O
+30mg	O
+/	O
+kg	O
+,	O
+i	O
+.	O
+v	O
+.	O
+)	O
+and	O
+blood	O
+samples	O
+were	O
+collected	O
+by	O
+cardiac	O
+puncture	O
+with	O
+10	O
+%	O
+EDTA	O
+.	O
+
+Total	O
+cell	O
+counts	O
+were	O
+carried	O
+out	O
+using	O
+diluting	O
+fluid	O
+in	O
+a	O
+Neubauer	O
+chamber	O
+.	O
+
+Differential	O
+countings	O
+were	O
+obtained	O
+using	O
+Rosenfeld	O
+-	O
+stained	O
+cytocentrifuge	O
+preparations	O
+,	O
+
+Bronchoalveolar	O
+lavage	O
+fluid	O
+.	O
+
+The	O
+guinea	B
+-	I
+pigs	I
+were	O
+killed	O
+by	O
+an	O
+overdose	O
+of	O
+sodium	O
+pentobarbitone	O
+and	O
+5ml	O
+of	O
+phosphate	O
+-	O
+buffered	O
+saline	O
+(	O
+PBS	O
+)	O
+containing	O
+0	O
+.	O
+5	O
+%	O
+sodium	O
+citrate	O
+(	O
+PBS	O
+/	O
+SC	O
+)	O
+,	O
+at	O
+room	O
+temperature	O
+,	O
+were	O
+instilled	O
+through	O
+a	O
+polyethylene	O
+cannula	O
+introduced	O
+into	O
+the	O
+trachea	O
+.	O
+
+The	O
+cells	O
+present	O
+in	O
+the	O
+bronchoalveolar	O
+lavage	O
+fluid	O
+(	O
+BALF	O
+)	O
+were	O
+recovered	O
+immediately	O
+.	O
+
+The	O
+procedure	O
+was	O
+repeated	O
+once	O
+.	O
+
+The	O
+leucocyte	O
+counts	O
+in	O
+the	O
+BAI	O
+_	O
+were	O
+determined	O
+as	O
+described	O
+above	O
+,	O
+Peritoneal	O
+cells	O
+:	O
+The	O
+cells	O
+from	O
+the	O
+peritoneal	O
+cavities	O
+were	O
+harvested	O
+by	O
+injection	O
+of	O
+10ml	O
+of	O
+PBS	O
+/	O
+SC	O
+into	O
+the	O
+peritoneum	O
+.	O
+
+Only	O
+5	O
+-	O
+8	O
+ml	O
+of	O
+the	O
+
+fluid	O
+was	O
+withdrawn	O
+for	O
+cell	O
+counts	O
+,	O
+as	O
+described	O
+above	O
+,	O
+
+Monoclonal	O
+antibodies	O
+:	O
+The	O
+rat	B
+monoclonal	O
+antibody	O
+TRFK	O
+-	O
+5	O
+was	O
+a	O
+generous	O
+gift	O
+from	O
+Dr	O
+P	O
+.	O
+
+Minoprio	O
+,	O
+Institut	O
+Pasteur	O
+,	O
+Paris	O
+.	O
+
+The	O
+neutralizing	O
+antibody	O
+was	O
+purified	O
+by	O
+precipitation	O
+with	O
+ammonium	O
+sulfate	O
+(	O
+45	O
+%	O
+)	O
+from	O
+ascites	O
+prepared	O
+in	O
+CD1	O
+nude	B
+mice	I
+(	O
+Charles	O
+River	O
+,	O
+St	O
+Aubin	O
+les	O
+Elbeuf	O
+,	O
+France	O
+)	O
+inoculated	O
+1	O
+week	O
+before	O
+the	O
+injection	O
+of	O
+hybridoma	O
+cells	O
+,	O
+with	O
+I	O
+ml	O
+of	O
+pristane	O
+(	O
+Sigma	O
+)	O
+.	O
+
+After	O
+precipitation	O
+and	O
+dialysis	O
+of	O
+the	O
+ascite	O
+fluid	O
+overnight	O
+against	O
+PBS	O
+,	O
+the	O
+dialysate	O
+was	O
+further	O
+purified	O
+on	O
+a	O
+Protein	O
+G1	O
+column	O
+(	O
+HiTrapTM	O
+,	O
+Pharmacia	O
+Upsala	O
+,	O
+Sweden	O
+)	O
+.	O
+
+Bone	O
+marrow	O
+cells	O
+:	O
+Bone	O
+marrow	O
+cells	O
+were	O
+collected	O
+by	O
+flushing	O
+the	O
+contents	O
+of	O
+the	O
+guinea	B
+-	I
+pig	I
+femur	O
+with	O
+10	O
+ml	O
+of	O
+PBS	O
+/	O
+SC	O
+.	O
+
+Total	O
+cell	O
+numbers	O
+were	O
+determined	O
+as	O
+above	O
+.	O
+
+In	O
+the	O
+differential	O
+cell	O
+counts	O
+the	O
+cell	O
+populations	O
+were	O
+divided	O
+into	O
+mature	O
+neutrophils	O
+,	O
+mature	O
+eosinophils	O
+and	O
+others	O
+(	O
+mainly	O
+precursors	O
+and	O
+mononuclear	O
+
+cells	O
+)	O
+,	O
+Histopathological	O
+studies	O
+:	O
+Tissues	O
+were	O
+removed	O
+from	O
+guinea	B
+-	I
+pigs	I
+at	O
+various	O
+times	O
+post	O
+-	O
+infection	O
+and	O
+immediately	O
+fixed	O
+in	O
+10	O
+%	O
+formalin	O
+.	O
+
+Tissues	O
+
+Eosinophil	O
+and	O
+cytokine	O
+depletion	O
+:	O
+Guinea	B
+-	I
+pigs	I
+were	O
+injected	O
+i	O
+.	O
+p	O
+.	O
+with	O
+TRFK	O
+-	O
+5	O
+or	O
+with	O
+the	O
+irrelevant	O
+antibody	O
+(	O
+rat	B
+IgG	O
+against	O
+total	O
+anti	O
+-	O
+human	B
+IgG	O
+)	O
+once	O
+,	O
+2mg	O
+/	O
+animal	O
+,	O
+at	O
+the	O
+time	O
+of	O
+infection	O
+or	O
+at	O
+different	O
+intervals	O
+(	O
+1	O
+,	O
+3	O
+,	O
+12	O
+or	O
+17	O
+days	O
+)	O
+thereafter	O
+.	O
+
+The	O
+animals	O
+in	O
+this	O
+group	O
+were	O
+sacririced	O
+18	O
+days	O
+after	O
+infection	O
+.	O
+liver	O
+:	O
+One	O
+lobule	O
+of	O
+was	O
+used	O
+to	O
+determine	O
+the	O
+larval	O
+each	O
+liver	O
+counts	O
+from	O
+infected	O
+guinea	B
+-	I
+pigs	I
+.	O
+
+Larval	O
+recovery	O
+
+Recovery	O
+
+of	O
+larvae	O
+from	O
+
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+25	O
+
+L	O
+.	O
+
+H	O
+.	O
+
+Faccioli	O
+et	O
+al	O
+.	O
+
+was	O
+evaluated	O
+as	O
+described	O
+by	O
+Kayes	O
+and	O
+Oaks	O
+,	O
+18	O
+with	O
+minor	O
+modifications	O
+.	O
+
+Briefly	O
+,	O
+the	O
+tissue	O
+was	O
+chopped	O
+and	O
+digested	O
+with	O
+pepsin	O
+-	O
+HC1	O
+(	O
+pH	O
+1	O
+.	O
+5	O
+
+1	O
+.	O
+8	O
+)	O
+for	O
+2h	O
+at	O
+37C	O
+.	O
+
+Larval	O
+counts	O
+for	O
+each	O
+sample	O
+were	O
+performed	O
+after	O
+centrifugation	O
+and	O
+examination	O
+of	O
+three	O
+100	O
+-	O
+l	O
+.	O
+tl	O
+samples	O
+under	O
+the	O
+light	O
+microscope	O
+.	O
+
+Statistical	O
+analysis	O
+:	O
+Data	O
+are	O
+presented	O
+as	O
+the	O
+mean	O
+_	O
++	O
+S	O
+.	O
+E	O
+.	O
+M	O
+.	O
+and	O
+were	O
+analysed	O
+statistically	O
+using	O
+the	O
+Mann	O
+-	O
+Whitney	O
+test	O
+for	O
+unpaired	O
+data	O
+.	O
+
+A	O
+p	O
+<	O
+0	O
+.	O
+05	O
+value	O
+was	O
+considered	O
+to	O
+be	O
+statistically	O
+
+significant	O
+.	O
+
+Results	O
+
+of	O
+eosinophil	O
+counts	O
+in	O
+blood	O
+bone	O
+marrow	O
+,	O
+BALF	O
+and	O
+peritoneum	O
+:	O
+Guinea	B
+-	I
+pigs	I
+infected	O
+with	O
+T	B
+.	I
+canis	I
+eggs	O
+showed	O
+a	O
+timedependent	O
+blood	O
+,	O
+bone	O
+-	O
+marrow	O
+,	O
+BAUV	O
+and	O
+peritoneal	O
+eosinophilia	O
+(	O
+Fig	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+results	O
+represent	O
+the	O
+mean	O
+of	O
+nine	O
+animals	O
+obtained	O
+in	O
+three	O
+different	O
+experiments	O
+.	O
+
+The	O
+eosinophil	O
+number	O
+Kinetics	O
+16	O
+
+increased	O
+significantly	O
+from	O
+0	O
+.	O
+55	O
++	O
+_	O
+0	O
+.	O
+37	O
+x	O
+105	O
+at	O
+the	O
+beginning	O
+of	O
+experiment	O
+to	O
+6	O
+.	O
+0	O
++	O
+_	O
+_	O
+1	O
+.	O
+03	O
+x	O
+105	O
+at	O
+6	O
+days	O
+post	O
+-	O
+infection	O
+,	O
+peaked	O
+at	O
+day	O
+18	O
+(	O
+12	O
+.	O
+0	O
+_	O
++	O
+2	O
+.	O
+31	O
+x	O
+105	O
+)	O
+,	O
+and	O
+decreased	O
+by	O
+day	O
+24	O
+(	O
+8	O
+.	O
+11	O
+2	O
+.	O
+85	O
+x	O
+105	O
+)	O
+(	O
+Fig	O
+.	O
+1A	O
+)	O
+.	O
+
+A	O
+rise	O
+in	O
+the	O
+percentage	O
+of	O
+mature	O
+eosinophils	O
+in	O
+bone	O
+marrow	O
+"	O
+was	O
+observed	O
+12	O
+days	O
+after	O
+infection	O
+(	O
+ranging	O
+from	O
+6	O
+2	O
+%	O
+to	O
+14	O
+2	O
+%	O
+)	O
+and	O
+peaked	O
+at	O
+18	O
+days	O
+(	O
+17	O
+2	O
+%	O
+)	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+As	O
+in	O
+blood	O
+,	O
+the	O
+number	O
+of	O
+eosinophils	O
+in	O
+BALF	O
+increased	O
+significantly	O
+from	O
+0	O
+.	O
+14	O
+0	O
+.	O
+06	O
+x	O
+105	O
+to	O
+1	O
+.	O
+37	O
+_	O
++	O
+0	O
+.	O
+35	O
+x	O
+105	O
+at	O
+6	O
+days	O
+after	O
+infection	O
+,	O
+reaching	O
+a	O
+peak	O
+at	O
+18	O
+days	O
+(	O
+10	O
+.	O
+23	O
+2	O
+.	O
+62	O
+x	O
+105	O
+)	O
+with	O
+an	O
+increase	O
+in	O
+relative	O
+number	O
+of	O
+as	O
+much	O
+as	O
+90	O
+%	O
+in	O
+eosinophil	O
+counts	O
+in	O
+relation	O
+to	O
+controls	O
+,	O
+and	O
+was	O
+still	O
+elevated	O
+at	O
+day	O
+24	O
+(	O
+9	O
+.	O
+07	O
+_	O
+_	O
+_	O
+3	O
+.	O
+47	O
+x	O
+10	O
+s	O
+)	O
+(	O
+Fig	O
+.	O
+1C	O
+)	O
+.	O
+
+The	O
+remaining	O
+cells	O
+in	O
+the	O
+BALF	O
+were	O
+alveolar	O
+macrophages	O
+,	O
+lymphocytes	O
+,	O
+mast	O
+cells	O
+and	O
+ciliated	O
+cells	O
+.	O
+
+In	O
+contrast	O
+to	O
+blood	O
+and	O
+BALF	O
+,	O
+the	O
+number	O
+of	O
+eosinophils	O
+in	O
+the	O
+peritoneal	O
+cavity	O
+increased	O
+significantl	O
+only	O
+at	O
+day	O
+12	O
+post	O
+-	O
+infection	O
+(	O
+onset	O
+,	O
+2	O
+.	O
+06	O
+1	O
+.	O
+04	O
+x	O
+105	O
+;	O
+day	O
+6	O
+,	O
+3	O
+.	O
+68	O
+_	O
++	O
+0	O
+.	O
+82	O
+x	O
+105	O
+;	O
+day	O
+12	O
+,	O
+5	O
+.	O
+77	O
++	O
+_	O
+1	O
+.	O
+12	O
+x	O
+10	O
+>	O
+;	O
+and	O
+increased	O
+progres	O
+
+_	O
+_	O
+_	O
+_	O
+_	O
+.	O
+
+(	O
+B	O
+)	O
+
+(	O
+AI	O
+Blood	O
+
+24	O
+20	O
+"	O
+
+Bone	O
+Marrow	O
+
+1612	O
+8	O
+
+4	O
+O0	O
+
+3	O
+
+6	O
+
+9	O
+
+12	O
+
+15	O
+
+111	O
+
+21	O
+
+24	O
+
+16	O
+
+(	O
+c	O
+)	O
+BALF	O
+
+16	O
+
+ID	O
+)	O
+Peritoneum	O
+
+12	O
+
+_	O
+_	O
+o	O
+
+12	O
+
+8	O
+
+4	O
+
+0	O
+3	O
+
+O6	O
+9	O
+
+12	O
+
+15	O
+
+16	O
+
+21	O
+
+24	O
+
+Days	O
+postinfoction	O
+
+FIG	O
+.	O
+
+1	O
+.	O
+
+Number	O
+of	O
+eosinophils	O
+in	O
+blood	O
+,	O
+BALF	O
+and	O
+peritoneal	O
+cavity	O
+,	O
+and	O
+percentage	O
+,	O
+of	O
+eosinophils	O
+in	O
+bone	O
+marrow	O
+of	O
+T	B
+.	I
+canisqnfected	I
+guinea	B
+-	I
+pigs	I
+.	O
+
+Values	O
+are	O
+the	O
+mean	O
+-	O
+t	O
+-	O
+S	O
+.	O
+E	O
+.	O
+M	O
+.	O
+
+(	O
+n	O
+=	O
+8	O
+to	O
+9	O
+)	O
+.	O
+
+Asterisks	O
+indicate	O
+a	O
+significant	O
+difference	O
+between	O
+infected	O
+and	O
+noninfected	O
+animals	O
+(	O
+n	O
+5	O
+6	O
+)	O
+.	O
+
+*	O
+p	O
+<	O
+0	O
+.	O
+05	O
+and	O
+*	O
+*	O
+p	O
+<	O
+0	O
+.	O
+01	O
+.	O
+
+26	O
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+in	O
+guinea	B
+-	I
+pig	I
+
+sively	O
+until	O
+day	O
+24	O
+,	O
+12	O
+.	O
+44	O
+4	O
+-	O
+2	O
+.	O
+72	O
+x	O
+105	O
+)	O
+(	O
+Fig	O
+.	O
+1D	O
+)	O
+.	O
+
+The	O
+percentage	O
+of	O
+eosinophils	O
+in	O
+some	O
+animals	O
+reached	O
+55	O
+%	O
+at	O
+the	O
+peak	O
+of	O
+infection	O
+.	O
+
+No	O
+increase	O
+in	O
+the	O
+number	O
+of	O
+mononuclear	O
+cells	O
+was	O
+seen	O
+in	O
+any	O
+compartment	O
+analysed	O
+.	O
+
+Larval	O
+counts	O
+:	O
+The	O
+percentage	O
+of	O
+inoculated	O
+T	B
+.	I
+canis	I
+larvae	O
+recovered	O
+by	O
+peptic	O
+digestion	O
+of	O
+the	O
+liver	O
+of	O
+experimental	O
+animals	O
+4	O
+h	O
+and	O
+1	O
+,	O
+2	O
+,	O
+3	O
+,	O
+4	O
+,	O
+9	O
+,	O
+12	O
+and	O
+18	O
+days	O
+after	O
+inoculation	O
+of	O
+500	O
+eggs	O
+per	O
+animal	O
+is	O
+shown	O
+in	O
+Fig	O
+.	O
+
+2	O
+.	O
+
+Most	O
+of	O
+the	O
+larvae	O
+were	O
+recovered	O
+2	O
+to	O
+4	O
+days	O
+after	O
+infection	O
+and	O
+10	O
+%	O
+recovery	O
+was	O
+also	O
+observed	O
+on	O
+day	O
+18	O
+in	O
+the	O
+liver	O
+of	O
+the	O
+animals	O
+.	O
+
+150	O
+
+120	O
+
+IL	O
+-	O
+5	O
+level	O
+in	O
+serum	O
+of	O
+infected	O
+animals	O
+:	O
+IL	O
+-	O
+5	O
+was	O
+measured	O
+in	O
+the	O
+serum	O
+of	O
+infected	O
+and	O
+normal	O
+guinea	B
+-	I
+pigs	I
+.	O
+
+Each	O
+time	O
+point	O
+in	O
+Fig	O
+.	O
+
+3	O
+represents	O
+the	O
+mean	O
+of	O
+results	O
+from	O
+three	O
+to	O
+five	O
+infected	O
+animals	O
+,	O
+and	O
+from	O
+six	O
+controls	O
+.	O
+
+Two	O
+peaks	O
+of	O
+IL5	O
+were	O
+present	O
+in	O
+the	O
+serum	O
+of	O
+infected	O
+guineapigs	B
+1	O
+day	O
+after	O
+infection	O
+(	O
+102	O
+_	O
+_	O
++	O
+22	O
+pg	O
+/	O
+ml	O
+)	O
+,	O
+and	O
+18	O
+days	O
+later	O
+(	O
+59	O
+7	O
+pg	O
+/	O
+ml	O
+)	O
+.	O
+
+The	O
+level	O
+of	O
+IL	O
+-	O
+5	O
+in	O
+the	O
+controls	O
+was	O
+31	O
+4	O
+-	O
+4	O
+pg	O
+/	O
+ml	O
+.	O
+
+Eosinophil	O
+numbers	O
+in	O
+infected	O
+animals	O
+treated	O
+with	O
+TRFK	O
+-	O
+5	O
+:	O
+When	O
+guinea	B
+-	I
+pigs	I
+received	O
+an	O
+i	O
+.	O
+p	O
+.	O
+injection	O
+of	O
+TRFK	O
+-	O
+5	O
+,	O
+the	O
+monoclonal	O
+antibody	O
+against	O
+IL	O
+-	O
+5	O
+,	O
+at	O
+the	O
+time	O
+of	O
+egg	O
+administration	O
+or	O
+1	O
+day	O
+later	O
+,	O
+the	O
+number	O
+of	O
+eosinophils	O
+in	O
+blood	O
+,	O
+BALF	O
+,	O
+peritoneal	O
+cavity	O
+and	O
+bone	O
+marrow	O
+was	O
+
+_	O
+
+30	O
+
+0	O
+
+0	O
+
+3	O
+
+6	O
+
+12	O
+
+18	O
+
+Days	O
+postinfection	O
+
+FIG	O
+.	O
+
+3	O
+.	O
+
+IL	O
+-	O
+5	O
+concentration	O
+in	O
+serum	O
+of	O
+T	B
+.	I
+caniinfected	I
+guineapigs	B
+(	O
+n	O
+3	O
+-	O
+5	O
+)	O
+.	O
+
+Basal	O
+IL	O
+-	O
+5	O
+concentrations	O
+were	O
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+31	O
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+pg	O
+/	O
+ml	O
+(	O
+n	O
+=	O
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+)	O
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+
+_	O
+
+24	O
+
+60	O
+
+50	O
+
+40	O
+
+0	O
+
+"	O
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+"	O
+
+1	O
+"	O
+
+0	O
+
+3	O
+
+6	O
+
+9	O
+
+12	O
+
+15	O
+
+18	O
+
+21	O
+
+24	O
+
+Days	O
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+.	O
+
+2	O
+.	O
+
+Percentage	O
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+-	I
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+-	O
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+.	O
+
+Data	O
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+five	O
+animals	O
+.	O
+
+drastically	O
+reduced	O
+,	O
+even	O
+when	O
+determined	O
+18	O
+days	O
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+infection	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+No	O
+inhibition	O
+of	O
+eosinophil	O
+counts	O
+was	O
+observed	O
+when	O
+the	O
+animals	O
+were	O
+inoculated	O
+with	O
+the	O
+irrelevant	O
+antibody	O
+at	O
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+of	O
+infection	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Fig	O
+.	O
+
+4	O
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+the	O
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+results	O
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+eosinophilia	O
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+when	O
+the	O
+antibody	O
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+given	O
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+17	O
+days	O
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+egg	O
+inoculation	O
+.	O
+
+The	O
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+a	O
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+inhibition	O
+in	O
+eosinophil	O
+counts	O
+in	O
+all	O
+the	O
+compartments	O
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+(	O
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+)	O
+.	O
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+However	O
+,	O
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+-	O
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+on	O
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+-	O
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+(	O
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+)	O
+,	O
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+only	O
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+the	O
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+(	O
+p	O
+=	O
+0	O
+.	O
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+)	O
+(	O
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+.	O
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+)	O
+.	O
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+A	O
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+-	O
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+(	O
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+0	O
+.	O
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+)	O
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+(	O
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+=	O
+0	O
+.	O
+222	O
+)	O
+.	O
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+Moreover	O
+,	O
+the	O
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+eosinophils	O
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+by	O
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+(	O
+p	O
+0	O
+.	O
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+)	O
+.	O
+
+As	O
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+Fig	O
+.	O
+
+4B	O
+,	O
+the	O
+behaviour	O
+of	O
+eosinotShilia	O
+in	O
+BALF	O
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+different	O
+from	O
+that	O
+observed	O
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+blood	O
+.	O
+
+Thus	O
+,	O
+to	O
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+the	O
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+infected	O
+animals	O
+,	O
+we	O
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+-	O
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+,	O
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+,	O
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+,	O
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+
+The	O
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+.	O
+
+In	O
+another	O
+group	O
+,	O
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+-	O
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+-	O
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+.	O
+
+When	O
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+1	O
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+of	O
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+(	O
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+.	O
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+)	O
+.	O
+
+These	O
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+of	O
+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+27	O
+
+L	O
+.	O
+
+H	O
+.	O
+
+Faccioli	O
+et	O
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+.	O
+
+Table	O
+1	O
+.	O
+
+Eosinophils	O
+in	O
+T	O
+.	O
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+guinea	B
+-	I
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+treated	O
+or	O
+untreated	O
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+-	O
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+Compartment	O
+
+Time	O
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+
+(	O
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+)	O
+
+Non18	O
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+treated	O
+
+Blood	O
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+12	O
+.	O
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+.	O
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+.	O
+08	O
+-	O
+t	O
+-	O
+2	O
+.	O
+85	O
+16	O
+.	O
+50	O
+4	O
+.	O
+42	O
+6	O
+.	O
+57	O
++	O
+_	O
+_	O
+1	O
+.	O
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+
+BALF	O
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+cavity	O
+
+12	O
+.	O
+31	O
+-	O
+I	O
+-	O
+2	O
+.	O
+35	O
+12	O
+.	O
+44	O
+2	O
+.	O
+33	O
+9	O
+6	O
+
+Bone	O
+marrow	O
+
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+Days	O
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+TRFK	O
+-	O
+5	O
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+egg	O
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+
+Irrelevant	O
+Ab	O
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+the	O
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+of	O
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+0	O
+
+3	O
+
+12	O
+
+17	O
+
+18	O
+
+(	O
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+)	O
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+(	O
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+=	O
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+)	O
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+(	O
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+=	O
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+(	O
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+(	O
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+)	O
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+(	O
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+=	O
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+)	O
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+0	O
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+14	O
+-	O
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+-	O
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+.	O
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+"	O
+
+0	O
+.	O
+26	O
+0	O
+.	O
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+0	O
+.	O
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+0	O
+.	O
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+-	O
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+-	O
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+.	O
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+"	O
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+0	O
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+15	O
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+0	O
+.	O
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+"	O
+
+2	O
+.	O
+59	O
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+0	O
+.	O
+80	O
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+4	O
+.	O
+36	O
+2	O
+.	O
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+
+13	O
+.	O
+32	O
+
+4	O
+.	O
+54	O
+
+O	O
+.	O
+
+15	O
+
+0	O
+.	O
+15	O
+*	O
+
+0	O
+.	O
+36	O
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+0	O
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+"	O
+
+1	O
+.	O
+22	O
+-	O
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+-	O
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+.	O
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+
+7	O
+.	O
+07	O
+-	O
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+-	O
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+.	O
+39	O
+
+15	O
+.	O
+24	O
+
+29	O
+.	O
+31	O
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++	O
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+.	O
+90	O
+16	O
+.	O
+09	O
+
+10	O
+.	O
+33	O
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++	O
+4	O
+.	O
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+.	O
+79	O
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+1	O
+.	O
+47	O
+-	O
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+-	O
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+.	O
+76	O
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+
+0	O
+.	O
+48	O
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+_	O
++	O
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+.	O
+35	O
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+
+0	O
+.	O
+46	O
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+.	O
+6	O
+
+0	O
+.	O
+27	O
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+1	O
+.	O
+3	O
+"	O
+
+2	O
+.	O
+89	O
+
+0	O
+.	O
+94	O
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+
+10	O
+.	O
+42	O
+
+4	O
+.	O
+00	O
+
+1	O
+.	O
+58	O
+"	O
+
+-	O
++	O
+
+1	O
+"	O
+
+1	O
+.	O
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+-	O
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+-	O
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+.	O
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+
++	O
+
+5	O
+
+15	O
+-	O
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+-	O
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+
+9	O
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++	O
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+2	O
+
+0	O
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+7	O
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+
+In	O
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+-	O
+t	O
+-	O
+_	O
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+.	O
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+.	O
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+.	O
+
+x	O
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+.	O
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+*	O
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+0	O
+.	O
+05	O
+.	O
+
+ml	O
+-	O
+1	O
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+and	O
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+-	O
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+-	O
+_	O
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+.	O
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+.	O
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+
+that	O
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+the	O
+first	O
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+of	O
+IL	O
+-	O
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+at	O
+1	O
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+Fig	O
+.	O
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+3	O
+,	O
+is	O
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+the	O
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+.	O
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+However	O
+,	O
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+-	O
+(	O
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+)	O
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+when	O
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+,	O
+17	O
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+(	O
+Fig	O
+.	O
+5	O
+)	O
+,	O
+showing	O
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+,	O
+the	O
+eosi18	O
+
+15x	O
+
+16	O
+
+12	O
+
+.	O
+_	O
+.	O
+
+0	O
+
+12	O
+
+o	O
+
+BIo	O
+o	O
+d	O
+
+BALF	O
+
+P	O
+e	O
+rit	O
+oneum	O
+
+Bone	O
+marrow	O
+
+24	O
+-	O
+(	O
+Is	O
+)	O
+
+1815	O
+
+E	O
+x	O
+
+20	O
+
+16	O
+
+o	O
+
+12	O
+/	O
+/	O
+/	O
+.	O
+
+o	O
+=	O
+o	O
+
+12	O
+
+0	O
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+
+O	O
+"	O
+
+BALF	O
+
+Peritoneum	O
+
+Bone	O
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+.	O
+
+4	O
+.	O
+
+Number	O
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+,	O
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+.	I
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+-	I
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+submitted	O
+or	O
+not	O
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+-	O
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+.	O
+
+(	O
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+)	O
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+/	O
+animal	O
+at	O
+3	O
+days	O
+post	O
+-	O
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+;	O
+(	O
+B	O
+)	O
+2	O
+mg	O
+/	O
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+-	O
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+.	O
+
+The	O
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+.	O
+
+Asterisks	O
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+(	O
+n	O
+=	O
+5	O
+-	O
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+)	O
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+-	O
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+(	O
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+=	O
+4	O
+-	O
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+)	O
+.	O
+
+*	O
+p	O
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+0	O
+.	O
+05	O
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+<	O
+0	O
+.	O
+01	O
+.	O
+
+28	O
+Mediators	O
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+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+in	O
+guinea	B
+-	I
+pig	I
+24	O
+
+E	O
+
+20	O
+
+heart	O
+;	O
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+not	O
+shown	O
+)	O
+and	O
+muscle	O
+,	O
+as	O
+reported	O
+by	O
+other	O
+investigators	O
+,	O
+8	O
+were	O
+infiltrated	O
+.	O
+
+The	O
+factors	O
+responsible	O
+for	O
+in	O
+vivo	O
+eosinophil	O
+accumulation	O
+at	O
+inflammatory	O
+sites	O
+have	O
+been	O
+
+0	O
+
+TRFK	O
+-	O
+5	O
+i	O
+.	O
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+.	O
+
+0	O
+
+3	O
+
+12	O
+17	O
+
+A	O
+
+B	O
+
+FIG	O
+.	O
+
+5	O
+.	O
+
+Number	O
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+eosinophils	O
+in	O
+BALF	O
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+.	O
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+guinea	B
+-	I
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+or	O
+not	O
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+-	O
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+.	O
+
+(	O
+A	O
+)	O
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+-	O
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+(	O
+B	O
+)	O
+24	O
+days	O
+after	O
+infection	O
+.	O
+
+Asterisks	O
+indicate	O
+a	O
+significant	O
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+infected	O
+control	O
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+from	O
+animals	O
+treated	O
+with	O
+TRFK	O
+-	O
+5	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+nophilia	O
+persists	O
+in	O
+lungs	O
+,	O
+probably	O
+by	O
+the	O
+secretion	O
+of	O
+IL	O
+-	O
+5	O
+from	O
+cells	O
+localized	O
+in	O
+the	O
+lung	O
+microenvironment	O
+,	O
+
+Histopathological	O
+analysis	O
+:	O
+The	O
+treatment	O
+of	O
+T	B
+.	I
+canis	I
+-	O
+infected	O
+animals	O
+with	O
+irrelevant	O
+antibody	O
+showed	O
+a	O
+widespread	O
+eosinophilic	O
+infiltration	O
+as	O
+in	O
+untreated	O
+animals	O
+(	O
+Fig	O
+.	O
+6A	O
+,	O
+B	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+treatment	O
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+animals	O
+with	O
+TRFK	O
+-	O
+5	O
+at	O
+the	O
+same	O
+time	O
+of	O
+infection	O
+,	O
+or	O
+1	O
+day	O
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+3	O
+days	O
+later	O
+ted	O
+to	O
+a	O
+complete	O
+inhibition	O
+of	O
+eosinophil	O
+infiltration	O
+in	O
+the	O
+lung	O
+parenchyma	O
+(	O
+Fig	O
+.	O
+6C	O
+)	O
+.	O
+
+By	O
+contrast	O
+,	O
+the	O
+mononuclear	O
+cell	O
+infiltration	O
+in	O
+the	O
+lungs	O
+was	O
+not	O
+modified	O
+.	O
+
+When	O
+the	O
+infected	O
+guinea	B
+-	I
+pigs	I
+received	O
+TRFK	O
+-	O
+5	O
+1	O
+day	O
+before	O
+sacrifice	O
+(	O
+or	O
+17	O
+days	O
+post	O
+-	O
+infection	O
+)	O
+,	O
+eosinophil	O
+infiltration	O
+in	O
+the	O
+lung	O
+parenchyma	O
+was	O
+also	O
+inhibited	O
+(	O
+Fig	O
+.	O
+6D	O
+)	O
+but	O
+not	O
+to	O
+the	O
+same	O
+extent	O
+as	O
+observed	O
+in	O
+the	O
+group	O
+receiving	O
+TRFK	O
+-	O
+5	O
+given	O
+at	O
+the	O
+time	O
+of	O
+infection	O
+or	O
+3	O
+days	O
+later	O
+.	O
+
+Thus	O
+,	O
+the	O
+histological	O
+determination	O
+of	O
+eosinophil	O
+infiltration	O
+in	O
+these	O
+lungs	O
+corroborates	O
+a	O
+reduction	O
+but	O
+not	O
+a	O
+sizeable	O
+inhibition	O
+of	O
+eosinophil	O
+numbers	O
+as	O
+observed	O
+in	O
+the	O
+BALF	O
+of	O
+the	O
+same	O
+infected	O
+animals	O
+,	O
+
+poorly	O
+defined	O
+,	O
+although	O
+T	O
+lymphocytes	O
+and	O
+mast	O
+cells	O
+appear	O
+to	O
+be	O
+involved	O
+in	O
+eosinophilia	O
+.	O
+
+9	O
+'	O
+2	O
+IL	O
+-	O
+5	O
+,	O
+a	O
+T	O
+cell	O
+-	O
+derived	O
+factor	O
+that	O
+regulates	O
+B	O
+cell	O
+functions	O
+,	O
+is	O
+an	O
+eosinophil	O
+differentiation	O
+factor11	O
+as	O
+well	O
+as	O
+a	O
+stimulating	O
+and	O
+survival	O
+-	O
+prolonging	O
+factor	O
+specific	O
+for	O
+eosinophils	O
+in	O
+vitro	O
+.	O
+
+2	O
+Also	O
+,	O
+several	O
+investigators	O
+have	O
+demonstrated	O
+that	O
+sTstemic	O
+eosinophilia	O
+in	O
+mice	B
+infected	O
+with	O
+parasites	O
+is	O
+mediated	O
+by	O
+IL	O
+-	O
+5	O
+produced	O
+in	O
+response	O
+to	O
+the	O
+infection	O
+.	O
+
+2	O
+'	O
+22	O
+In	O
+the	O
+present	O
+study	O
+,	O
+the	O
+i	O
+.	O
+p	O
+.	O
+administration	O
+of	O
+the	O
+TRFK	O
+-	O
+5	O
+antibody	O
+markedly	O
+inhibited	O
+the	O
+widespread	O
+eosinophilia	O
+observed	O
+in	O
+T	B
+.	I
+canis	I
+-	O
+infected	O
+guinea	B
+-	I
+pigs	I
+,	O
+indicating	O
+that	O
+IL5	O
+participated	O
+in	O
+a	O
+guinea	B
+-	I
+pig	I
+model	O
+of	O
+VLMS	O
+eosinophJlia	O
+.	O
+
+Most	O
+of	O
+the	O
+T	B
+.	I
+canis	I
+larvae	O
+which	O
+penetrated	O
+the	O
+intestinal	O
+wall	O
+had	O
+migrated	O
+into	O
+the	O
+liver	O
+within	O
+72h	O
+after	O
+inoculation	O
+as	O
+demonstrated	O
+here	O
+and	O
+elsewhere	O
+.	O
+
+2	O
+It	O
+is	O
+apparently	O
+during	O
+this	O
+interval	O
+that	O
+the	O
+worm	O
+provides	O
+the	O
+signals	O
+to	O
+cytokine	O
+-	O
+producing	O
+cells	O
+,	O
+which	O
+in	O
+turn	O
+trigger	O
+increased	O
+serum	O
+levels	O
+of	O
+specific	O
+cytokine	O
+as	O
+demonstrated	O
+here	O
+for	O
+IL	O
+-	O
+5	O
+,	O
+24	O
+to	O
+72	O
+h	O
+after	O
+infection	O
+.	O
+
+The	O
+signals	O
+may	O
+be	O
+provided	O
+directly	O
+by	O
+the	O
+invading	O
+parasite	O
+or	O
+by	O
+cells	O
+in	O
+response	O
+to	O
+the	O
+parasite	O
+.	O
+
+The	O
+cytokine	O
+pattern	O
+that	O
+develops	O
+at	O
+this	O
+early	O
+stage	O
+,	O
+probably	O
+induced	O
+by	O
+a	O
+T	O
+-	O
+cell	O
+independent	O
+pathway	O
+,	O
+may	O
+also	O
+influence	O
+the	O
+pattern	O
+of	O
+T	O
+cell	O
+differentiation	O
+into	O
+a	O
+Th2	O
+type	O
+,	O
+which	O
+may	O
+be	O
+responsible	O
+for	O
+the	O
+second	O
+peak	O
+of	O
+IL	O
+-	O
+5	O
+observed	O
+in	O
+our	O
+experimental	O
+model	O
+(	O
+Fig	O
+.	O
+3	O
+)	O
+,	O
+although	O
+a	O
+second	O
+cycle	O
+of	O
+larval	O
+invasion	O
+(	O
+Fig	O
+.	O
+2	O
+)	O
+with	O
+a	O
+rapid	O
+peak	O
+of	O
+IL	O
+-	O
+5	O
+liberation	O
+cannot	O
+be	O
+ruled	O
+out	O
+.	O
+
+Discussion	O
+The	O
+results	O
+of	O
+the	O
+present	O
+study	O
+show	O
+that	O
+in	O
+our	O
+experimental	O
+model	O
+widespread	O
+eosinophilia	O
+follows	O
+the	O
+infection	O
+of	O
+guinea	B
+-	I
+pigs	I
+with	O
+second	O
+stage	O
+eggs	O
+from	O
+T	B
+.	I
+canis	I
+,	O
+as	O
+also	O
+noted	O
+in	O
+humans	B
+and	O
+in	O
+other	O
+experimental	O
+animals	O
+.	O
+
+7	O
+'	O
+7	O
+T	B
+.	I
+canis	I
+is	O
+a	O
+potent	O
+stimulus	O
+for	O
+systemic	O
+eosinophilia	O
+,	O
+since	O
+blood	O
+,	O
+BALF	O
+,	O
+peritoneum	O
+and	O
+all	O
+tissues	O
+examined	O
+(	O
+kidney	O
+,	O
+eyes	O
+,	O
+spleen	O
+,	O
+thymus	O
+,	O
+
+Thus	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+the	O
+eosinophilia	O
+against	O
+helminth	O
+larvae	O
+may	O
+be	O
+initiated	O
+by	O
+the	O
+release	O
+of	O
+IL	O
+-	O
+5	O
+when	O
+the	O
+parasites	O
+migrate	O
+from	O
+the	O
+intestine	O
+to	O
+the	O
+liver	O
+by	O
+stimulation	O
+of	O
+specific	O
+cell	O
+populations	O
+.	O
+
+Then	O
+,	O
+an	O
+early	O
+release	O
+of	O
+IL	O
+-	O
+5	O
+quickly	O
+induces	O
+eosinophil	O
+recruitment	O
+,	O
+probably	O
+first	O
+from	O
+the	O
+stored	O
+mature	O
+eosinophil	O
+pool	O
+from	O
+vascular	O
+endothelium	O
+or	O
+by	O
+the	O
+mobilization	O
+of	O
+eosinophils	O
+from	O
+extravascular	O
+sites	O
+to	O
+the	O
+blood	O
+.	O
+
+This	O
+fact	O
+could	O
+explain	O
+why	O
+we	O
+found	O
+increased	O
+eosinophils	O
+first	O
+in	O
+blood	O
+and	O
+later	O
+in	O
+other	O
+compartments	O
+.	O
+
+The	O
+early	O
+IL	O
+-	O
+5	O
+release	O
+may	O
+also	O
+serve	O
+as	O
+a	O
+signal	O
+for	O
+eosinophil	O
+differentiation	O
+and	O
+maturation	O
+in	O
+bone	O
+marrow	O
+.	O
+
+The	O
+time	O
+
+inteeeal	O
+observed	O
+between	O
+the	O
+first	O
+peak	O
+of	O
+IL	O
+-	O
+5	O
+release	O
+and	O
+the	O
+increase	O
+of	O
+eosinophils	O
+in	O
+blood	O
+coincides	O
+with	O
+that	O
+reported	O
+to	O
+be	O
+necessary	O
+for	O
+eosinophil	O
+differentiation	O
+and	O
+maturation	O
+in	O
+vitro	O
+.	O
+
+12Increased	O
+eosinophil	O
+production	O
+and	O
+liberation	O
+into	O
+blood	O
+and	O
+other	O
+tissues	O
+occurs	O
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+29	O
+
+L	O
+.	O
+
+H	O
+.	O
+
+Faccioli	O
+et	O
+al	O
+.	O
+
+FIG	O
+.	O
+
+6	O
+.	O
+
+(	O
+A	O
+)	O
+photomicrographs	O
+of	O
+lung	O
+parenchyma	O
+from	O
+guinea	B
+-	I
+pigs	I
+infected	O
+for	O
+18	O
+days	O
+with	O
+T	B
+.	I
+cani	I
+,	O
+,	O
+(	O
+B	O
+)	O
+infected	O
+animals	O
+which	O
+were	O
+treated	O
+with	O
+irrelevant	O
+antibody	O
+at	O
+the	O
+time	O
+of	O
+infection	O
+;	O
+(	O
+C	O
+)	O
+infected	O
+animals	O
+which	O
+were	O
+treated	O
+with	O
+the	O
+mAb	O
+TRFK	O
+-	O
+5	O
+at	O
+3	O
+days	O
+after	O
+infection	O
+;	O
+(	O
+D	O
+)	O
+mAb	O
+administration	O
+17	O
+days	O
+after	O
+infection	O
+.	O
+
+The	O
+animals	O
+were	O
+sacrificed	O
+18	O
+days	O
+after	O
+infection	O
+.	O
+
+Note	O
+the	O
+intense	O
+eosinophil	O
+infiltration	O
+into	O
+the	O
+lung	O
+in	O
+A	O
+and	O
+B	O
+,	O
+the	O
+inhibition	O
+of	O
+eosinophils	O
+in	O
+C	O
+and	O
+the	O
+reduction	O
+of	O
+eosinophils	O
+in	O
+D	O
+.	O
+
+thereafter	O
+.	O
+
+Thus	O
+,	O
+early	O
+and	O
+later	O
+IL	O
+-	O
+5	O
+release	O
+provides	O
+a	O
+necessary	O
+level	O
+of	O
+this	O
+cytokine	O
+,	O
+which	O
+is	O
+involved	O
+in	O
+the	O
+maintenance	O
+of	O
+eosinophilia	O
+.	O
+
+We	O
+may	O
+assume	O
+that	O
+the	O
+inhibition	O
+of	O
+the	O
+first	O
+peak	O
+of	O
+IL	O
+-	O
+5	O
+release	O
+by	O
+TRFK	O
+-	O
+5	O
+does	O
+not	O
+permit	O
+the	O
+subsequent	O
+T	O
+cell	O
+stimulation	O
+and	O
+differentiation	O
+.	O
+
+This	O
+may	O
+explain	O
+the	O
+long	O
+-	O
+lasting	O
+effect	O
+of	O
+TRFK5	O
+treatment	O
+observed	O
+here	O
+and	O
+also	O
+reported	O
+by	O
+others	O
+.	O
+
+8	O
+In	O
+agreement	O
+with	O
+our	O
+results	O
+,	O
+there	O
+is	O
+an	O
+important	O
+observation	O
+of	O
+Svetic	O
+et	O
+al	O
+.	O
+
+24	O
+showing	O
+that	O
+a	O
+specific	O
+and	O
+highly	O
+reproducible	O
+IL	O
+-	O
+5	O
+gene	O
+expression	O
+pattern	O
+is	O
+detectable	O
+in	O
+Peyer	O
+'	O
+s	O
+patches	O
+by	O
+6	O
+to	O
+12h	O
+after	O
+Heligmosomoides	B
+polygyrus	I
+infection	O
+.	O
+
+The	O
+early	O
+increase	O
+in	O
+IL	O
+-	O
+5	O
+gene	O
+expression	O
+after	O
+infection	O
+was	O
+probably	O
+T	O
+cell	O
+-	O
+independent	O
+,	O
+inasmuch	O
+as	O
+it	O
+was	O
+obseeeed	O
+in	O
+Peyer	O
+'	O
+s	O
+patches	O
+of	O
+congenitally	O
+athymic	O
+mice	B
+and	O
+of	O
+conventional	O
+mice	B
+treated	O
+with	O
+anti	O
+-	O
+CD4	O
+30	O
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+and	O
+anti	O
+-	O
+CD8	O
+mAb	O
+.	O
+
+Moreover	O
+,	O
+Kusama	O
+eta	O
+/	O
+.	O
+
+25	O
+have	O
+observed	O
+two	O
+peaks	O
+of	O
+eosinophilia	O
+in	O
+normal	O
+and	O
+athymic	O
+mice	B
+,	O
+and	O
+suggested	O
+that	O
+IL	O
+-	O
+5	O
+observed	O
+in	O
+the	O
+first	O
+peak	O
+was	O
+produced	O
+by	O
+cells	O
+other	O
+than	O
+CD4	O
+T	O
+cells	O
+,	O
+since	O
+anti	O
+-	O
+CD4	O
+and	O
+anti	O
+-	O
+CD3	O
+mAb	O
+reduced	O
+only	O
+the	O
+second	O
+peak	O
+of	O
+eosinophilia	O
+in	O
+normal	O
+mice	B
+and	O
+slightly	O
+reduced	O
+the	O
+first	O
+peak	O
+of	O
+eosinophilia	O
+in	O
+both	O
+normal	O
+and	O
+nu	O
+/	O
+nu	O
+mice	B
+.	O
+
+The	O
+local	O
+lung	O
+cells	O
+producing	O
+IL	O
+-	O
+5	O
+may	O
+also	O
+help	O
+us	O
+to	O
+explain	O
+the	O
+reason	O
+why	O
+12	O
+,	O
+17	O
+or	O
+18	O
+days	O
+post	O
+-	O
+infection	O
+TRFK	O
+-	O
+5	O
+treatment	O
+only	O
+partially	O
+inhibits	O
+,	O
+or	O
+does	O
+not	O
+inhibit	O
+eosinophil	O
+infiltration	O
+into	O
+the	O
+lungs	O
+,	O
+as	O
+demonstrated	O
+in	O
+Figs	O
+5	O
+and	O
+6	O
+.	O
+
+We	O
+may	O
+suggest	O
+that	O
+when	O
+eosinophils	O
+have	O
+already	O
+migrated	O
+to	O
+the	O
+lungs	O
+,	O
+TRFK	O
+-	O
+5	O
+has	O
+no	O
+power	O
+to	O
+inhibit	O
+eosinophilia	O
+,	O
+which	O
+is	O
+also	O
+under	O
+control	O
+of	O
+local	O
+lung	O
+cells	O
+producing	O
+IL	O
+-	O
+5	O
+.	O
+
+In	O
+this	O
+way	O
+,	O
+only	O
+one	O
+later	O
+TRFK	O
+
+1996	O
+
+IL	O
+-	O
+5	O
+drives	O
+eosinophils	O
+in	O
+guinea	B
+-	I
+pig	I
+
+5	O
+treatment	O
+may	O
+not	O
+be	O
+sufficient	O
+to	O
+modify	O
+the	O
+lung	O
+parenchyma	O
+microenvironment	O
+,	O
+since	O
+T	B
+.	I
+canis	I
+antigens	O
+have	O
+already	O
+stimulated	O
+some	O
+cell	O
+populations	O
+to	O
+produce	O
+IL	O
+-	O
+5	O
+,	O
+as	O
+demonstrated	O
+by	O
+Kusama	O
+et	O
+aL25These	O
+results	O
+suggest	O
+that	O
+eosinophilia	O
+in	O
+lungs	O
+is	O
+under	O
+the	O
+control	O
+of	O
+different	O
+factors	O
+when	O
+compared	O
+to	O
+that	O
+observed	O
+in	O
+blood	O
+and	O
+the	O
+peritoneal	O
+cavity	O
+.	O
+
+One	O
+of	O
+the	O
+most	O
+important	O
+results	O
+obtained	O
+here	O
+was	O
+the	O
+inhibition	O
+of	O
+circulating	O
+eosinophil	O
+numbers	O
+by	O
+the	O
+different	O
+mAb	O
+treatments	O
+,	O
+even	O
+when	O
+the	O
+antibody	O
+was	O
+given	O
+at	O
+the	O
+peak	O
+of	O
+blood	O
+eosinophilia	O
+,	O
+which	O
+was	O
+accompanied	O
+by	O
+an	O
+increase	O
+of	O
+mature	O
+eosinophils	O
+in	O
+bone	O
+marrow	O
+.	O
+
+This	O
+suggests	O
+that	O
+IL	O
+-	O
+5	O
+,	O
+apart	O
+from	O
+being	O
+required	O
+for	O
+the	O
+terminal	O
+differentiation	O
+of	O
+eosinophils	O
+in	O
+bone	O
+marrow	O
+,	O
+26	O
+is	O
+also	O
+likely	O
+to	O
+drive	O
+eosinophils	O
+from	O
+the	O
+bone	O
+marrow	O
+to	O
+the	O
+blood	O
+and	O
+then	O
+to	O
+the	O
+tissues	O
+,	O
+probably	O
+by	O
+upregulating	O
+VLA	O
+-	O
+4	O
+expression	O
+in	O
+eosinophils	O
+.	O
+
+Moser	O
+et	O
+aL	O
+have	O
+demonstrated	O
+that	O
+in	O
+order	O
+to	O
+acquire	O
+the	O
+ability	O
+to	O
+transmigrate	O
+,	O
+eosinophils	O
+must	O
+be	O
+primed	O
+with	O
+cytokines	O
+such	O
+as	O
+IL	O
+-	O
+5	O
+,	O
+IL	O
+-	O
+3	O
+or	O
+GM	O
+-	O
+CSF	O
+for	O
+expression	O
+of	O
+adhesion	O
+molecules	O
+such	O
+as	O
+VI	O
+-	O
+4	O
+.	O
+
+Recently	O
+,	O
+Pretolani	O
+et	O
+al	O
+.	O
+
+27	O
+have	O
+indeed	O
+shown	O
+that	O
+an	O
+anti	O
+-	O
+VLA	O
+-	O
+4	O
+antibody	O
+suppresses	O
+eosinophil	O
+recruitment	O
+to	O
+lung	O
+in	O
+the	O
+guinea	B
+-	I
+pig	I
+and	O
+,	O
+as	O
+a	O
+consequence	O
+,	O
+inhibits	O
+the	O
+accompanying	O
+bronchopulmonary	O
+hyperresponsiveness	O
+.	O
+
+tant	O
+in	O
+protective	O
+immunity	O
+to	O
+a	O
+gastrointestinal	O
+nematode	O
+infection	O
+in	O
+mice	B
+.	O
+
+Proc	O
+Natl	O
+Acad	O
+Sci	O
+USA	O
+1991	O
+;	O
+88	O
+=	O
+5513	O
+-	O
+5517	O
+.	O
+
+11	O
+.	O
+
+Yamaguchi	O
+A	O
+,	O
+Suda	O
+T	O
+,	O
+Suda	O
+J	O
+,	O
+et	O
+al	O
+.	O
+
+Purified	O
+interleukin	O
+(	O
+IL	O
+-	O
+5	O
+)	O
+supports	O
+the	O
+terminal	O
+differentiation	O
+and	O
+proliferation	O
+of	O
+murine	B
+eosinophilic	O
+
+precursors	O
+.	O
+
+J	O
+Exp	O
+Med	O
+1988	O
+;	O
+16	O
+'	O
+7	O
+:	O
+43	O
+-	O
+56	O
+.	O
+
+12	O
+.	O
+
+Yamaguchi	O
+Y	O
+,	O
+Hayashi	O
+Y	O
+,	O
+Sugama	O
+Y	O
+,	O
+et	O
+al	O
+.	O
+
+Highly	O
+purified	O
+murine	B
+interleukin	O
+(	O
+IL	O
+-	O
+5	O
+)	O
+stimulates	O
+eosinophil	O
+function	O
+and	O
+prolongs	O
+in	O
+vitro	O
+survival	O
+.	O
+
+IL	O
+-	O
+5	O
+as	O
+an	O
+eosinophil	O
+chemotactic	O
+factor	O
+.	O
+
+J	O
+Exp	O
+Med	O
+1988	O
+;	O
+16	O
+'	O
+7	O
+:	O
+17371752	O
+.	O
+
+13	O
+.	O
+
+Rothenberg	O
+ME	O
+,	O
+Petersen	O
+J	O
+,	O
+Stevens	O
+RL	O
+,	O
+Silberstein	O
+DS	O
+,	O
+McKenzie	O
+DT	O
+,	O
+Austen	O
+KF	O
+,	O
+Owen	O
+WF	O
+.	O
+
+IL	O
+-	O
+5	O
+-	O
+dependent	O
+conversion	O
+of	O
+normodense	O
+human	B
+eosinophils	O
+to	O
+the	O
+hypodense	O
+phenotype	O
+uses	O
+3T3	O
+fibroblasts	O
+for	O
+enhanced	O
+viability	O
+,	O
+accelerated	O
+hypodensity	O
+,	O
+and	O
+sustained	O
+antibodydependent	O
+cytotoxicity	O
+.	O
+
+J	O
+Immuno11989	O
+;	O
+143	O
+;	O
+2311	O
+-	O
+2316	O
+.	O
+
+14	O
+.	O
+
+Collins	O
+PD	O
+,	O
+Weg	O
+VB	O
+,	O
+Faccioli	O
+LH	O
+,	O
+Watson	O
+ML	O
+,	O
+Moqbel	O
+R	O
+,	O
+Williams	O
+TJ	O
+.	O
+
+Eosinophil	O
+accumulation	O
+induced	O
+by	O
+human	B
+interleukin	O
+-	O
+8	O
+in	O
+the	O
+guinea	B
+pig	I
+in	O
+vivo	O
+.	O
+
+Immunology	O
+1993	O
+;	O
+'	O
+7	O
+}	O
+;	O
+312	O
+-	O
+318	O
+.	O
+
+15	O
+.	O
+
+Sehmi	O
+R	O
+,	O
+Wardlavo	O
+AJ	O
+,	O
+Cromwell	O
+O	O
+,	O
+Kurihara	O
+K	O
+,	O
+Waltmann	O
+P	O
+,	O
+Kay	O
+AB	O
+.	O
+
+Interleukin	O
+-	O
+5	O
+selectively	O
+enhances	O
+the	O
+chemotactic	O
+response	O
+of	O
+eosinophils	O
+obtained	O
+from	O
+normal	O
+but	O
+not	O
+eosinophilic	O
+subjects	O
+.	O
+
+Blood	O
+1992	O
+;	O
+'	O
+79	O
+;	O
+2952	O
+-	O
+2959	O
+.	O
+
+16	O
+.	O
+
+Moser	O
+R	O
+,	O
+Fehr	O
+J	O
+,	O
+Bruijnzeel	O
+PLB	O
+.	O
+
+IL	O
+-	O
+4	O
+controls	O
+the	O
+selective	O
+endotheliumdriven	O
+transmigration	O
+of	O
+eosinophils	O
+from	O
+allergic	O
+individuals	O
+.	O
+
+J	O
+Immunol	O
+1992	O
+;	O
+149	O
+:	O
+1432	O
+-	O
+1438	O
+.	O
+
+17	O
+.	O
+
+Olson	O
+LJ	O
+,	O
+Schulz	O
+CW	O
+.	O
+
+Nematode	O
+induced	O
+hypersensitivity	O
+reactions	O
+in	O
+guinea	B
+pigs	I
+:	O
+onset	O
+of	O
+eosinophilia	O
+and	O
+positive	O
+Schultz	O
+-	O
+Dale	O
+reactions	O
+following	O
+graded	O
+infection	O
+with	O
+Toxocara	B
+canis	I
+.	O
+
+Ann	O
+N	O
+Y	O
+Acad	O
+Sci	O
+1963	O
+;	O
+113	O
+;	O
+440	O
+-	O
+455	O
+.	O
+
+18	O
+.	O
+
+Kayes	O
+SG	O
+,	O
+Oaks	O
+
+JA	O
+.	O
+
+Development	O
+
+of	O
+the	O
+granulomatous	O
+response	O
+in	O
+
+murine	B
+toxocariasis	O
+.	O
+
+I	O
+.	O
+
+Initial	O
+events	O
+.	O
+
+Am	O
+J	O
+Patho11978	O
+;	O
+,	O
+}	O
+3	O
+;	O
+
+277	O
+-	O
+294	O
+.	O
+
+19	O
+.	O
+
+Basten	O
+A	O
+,	O
+Beeson	O
+PB	O
+.	O
+
+Mechanisms	O
+of	O
+eosinophilia	O
+.	O
+
+II	O
+.	O
+
+Role	O
+of	O
+the	O
+lymphocyte	O
+.	O
+
+J	O
+Exp	O
+Med	O
+1970	O
+;	O
+131	O
+;	O
+1288	O
+-	O
+1305	O
+.	O
+
+20	O
+.	O
+
+Plaut	O
+M	O
+,	O
+Pierce	O
+JH	O
+,	O
+Watson	O
+CJ	O
+,	O
+Hanley	O
+-	O
+Hyde	O
+J	O
+,	O
+Nordan	O
+RP	O
+,	O
+Paul	O
+WE	O
+.	O
+
+Mast	O
+cell	O
+lines	O
+produce	O
+lymphokines	O
+in	O
+response	O
+to	O
+cross	O
+-	O
+linkage	O
+of	O
+Fc	O
+epsilon	O
+RI	O
+or	O
+to	O
+calcium	O
+ionophoras	O
+.	O
+
+Nature	O
+1989	O
+;	O
+339	O
+:	O
+64	O
+-	O
+67	O
+.	O
+
+is	O
+21	O
+.	O
+
+Sher	O
+A	O
+,	O
+Coffman	O
+RL	O
+,	O
+Hieny	O
+S	O
+,	O
+Scott	O
+P	O
+,	O
+Cheever	O
+AW	O
+.	O
+
+Interleukin	O
+required	O
+for	O
+the	O
+blood	O
+and	O
+tissue	O
+eosinophilia	O
+but	O
+not	O
+granuloma	O
+formation	O
+induced	O
+by	O
+infection	O
+with	O
+Schistosoma	B
+mansoni	I
+.	O
+
+Proc	O
+Natl	O
+Acad	O
+Sci	O
+USA	O
+1990	O
+;	O
+8	O
+'	O
+7	O
+;	O
+61	O
+-	O
+65	O
+.	O
+
+22	O
+.	O
+
+Herndon	O
+FJ	O
+,	O
+Kayes	O
+SG	O
+.	O
+
+Depletion	O
+of	O
+eosinophils	O
+by	O
+anti	O
+-	O
+IL	O
+-	O
+5	O
+monoclonal	O
+antibody	O
+treatment	O
+of	O
+mice	B
+infected	O
+with	O
+Trichinella	B
+spiralis	I
+does	O
+not	O
+alter	O
+parasite	O
+burden	O
+or	O
+immunologic	O
+resistance	O
+to	O
+reinfection	O
+.	O
+
+J	O
+Immuno11992	O
+;	O
+149	O
+:	O
+3642	O
+-	O
+3647	O
+.	O
+
+23	O
+.	O
+
+Oshima	O
+T	O
+.	O
+Standardization	O
+of	O
+techniques	O
+for	O
+infecting	O
+mice	B
+with	O
+Tox24	O
+.	O
+ocara	O
+canis	O
+and	O
+observations	O
+on	O
+the	O
+normal	O
+migration	O
+routes	O
+of	O
+the	O
+larvae	O
+.	O
+
+J	O
+Parasito11961	O
+;	O
+4	O
+'	O
+7	O
+=	O
+652	O
+.	O
+
+Svetic	O
+A	O
+,	O
+Madden	O
+KB	O
+,	O
+Zhou	O
+XD	O
+,	O
+et	O
+al	O
+.	O
+
+A	O
+primary	O
+intestinal	O
+helminthic	O
+infection	O
+rapidly	O
+induces	O
+a	O
+gut	O
+-	O
+associated	O
+elevation	O
+of	O
+Th2	O
+-	O
+associated	O
+cytokines	O
+and	O
+IL	O
+-	O
+3	O
+.	O
+
+J	O
+Immuno11993	O
+;	O
+150	O
+:	O
+3434	O
+-	O
+3441	O
+.	O
+
+Kusama	O
+Y	O
+,	O
+Takamoto	O
+M	O
+,	O
+Kasahara	O
+T	O
+,	O
+Takatsu	O
+K	O
+,	O
+Nariuchi	O
+H	O
+,	O
+Sugane	O
+K	O
+.	O
+Mechanisms	O
+of	O
+eosinophilia	O
+in	O
+BALB	O
+/	O
+c	O
+-	O
+nu	O
+/	O
++	O
+and	O
+congenitally	O
+athymic	O
+BALB	O
+/	O
+c	O
+-	O
+nu	O
+/	O
+nu	O
+mice	B
+infected	O
+with	O
+Toxocara	B
+canis	I
+.	O
+
+Immunology	O
+1995	O
+;	O
+84	O
+;	O
+461	O
+-	O
+468	O
+.	O
+
+Rennick	O
+DM	O
+,	O
+Thompson	O
+-	O
+Snipes	O
+L	O
+,	O
+Coffman	O
+RL	O
+,	O
+Seymour	O
+BWP	O
+,	O
+Jackson	O
+JD	O
+,	O
+Hudak	O
+S	O
+.	O
+
+In	O
+vivo	O
+administration	O
+of	O
+antibody	O
+to	O
+interleukin	O
+-	O
+5	O
+inhibits	O
+increased	O
+generation	O
+of	O
+eosinophils	O
+and	O
+their	O
+progenitors	O
+in	O
+bone	O
+marrow	O
+of	O
+parasitized	O
+mice	B
+.	O
+
+Blood	O
+1990	O
+;	O
+'	O
+76	O
+:	O
+312	O
+-	O
+316	O
+.	O
+
+Petrolani	O
+M	O
+,	O
+Ruffle	O
+C	O
+,	O
+Lapa	O
+e	O
+Silva	O
+JR	O
+,	O
+Joseph	O
+D	O
+,	O
+Lobb	O
+RR	O
+,	O
+Boris	O
+Vargaftig	O
+B	O
+.	O
+Antibody	O
+to	O
+very	O
+late	O
+activation	O
+antigen	O
+4	O
+prevents	O
+antigen	O
+-	O
+induced	O
+bronchial	O
+hyperreactivity	O
+and	O
+cellular	O
+infiltration	O
+in	O
+guinea	B
+pig	I
+airways	O
+.	O
+
+J	O
+Exp	O
+Med	O
+1994	O
+;	O
+180	O
+=	O
+795	O
+-	O
+805	O
+.	O
+
+References	O
+25	O
+.	O
+
+1	O
+.	O
+
+Nutman	O
+
+2	O
+.	O
+
+3	O
+.	O
+
+4	O
+.	O
+
+5	O
+.	O
+
+6	O
+.	O
+
+7	O
+.	O
+
+8	O
+.	O
+
+9	O
+.	O
+
+TB	O
+,	O
+Ottesen	O
+EA	O
+,	O
+Cohen	O
+SG	O
+.	O
+
+The	O
+eosinophil	O
+,	O
+eosinophilia	O
+,	O
+and	O
+eosinophil	O
+-	O
+related	O
+disorders	O
+.	O
+
+Allergy	O
+Proc	O
+1989	O
+;	O
+10	O
+;	O
+47	O
+-	O
+62	O
+.	O
+
+Glickman	O
+LT	O
+,	O
+Schantz	O
+PM	O
+.	O
+
+Epidemiology	O
+and	O
+pathogenesis	O
+of	O
+zoonotic	O
+toxocariasis	O
+.	O
+
+Epidem	O
+Rev	O
+1981	O
+;	O
+3	O
+=	O
+230	O
+-	O
+250	O
+.	O
+
+Beaver	O
+P	O
+,	O
+Snyder	O
+H	O
+,	O
+Carrera	O
+G	O
+,	O
+Dent	O
+J	O
+,	O
+Lafferty	O
+J	O
+.	O
+Chronic	O
+eosinophilia	O
+due	O
+to	O
+visceral	O
+larva	O
+migrans	O
+.	O
+
+Pediatrics	O
+1952	O
+;	O
+9	O
+:	O
+7	O
+-	O
+19	O
+.	O
+
+Limaye	O
+AP	O
+,	O
+Abrams	O
+JS	O
+,	O
+Silver	O
+JE	O
+,	O
+Ottesen	O
+EA	O
+,	O
+Nutman	O
+TB	O
+.	O
+
+Regulation	O
+of	O
+parasite	O
+-	O
+induced	O
+eosinophilia	O
+:	O
+selectively	O
+increased	O
+interleukin	O
+production	O
+in	O
+helminth	O
+-	O
+infected	O
+patients	B
+.	O
+
+J	O
+Exp	O
+Med	O
+1990	O
+;	O
+l	O
+'	O
+7	O
+:	O
+a	O
+;	O
+399	O
+-	O
+402	O
+.	O
+
+Steel	O
+C	O
+,	O
+Nutman	O
+TB	O
+.	O
+
+Regulation	O
+of	O
+IL	O
+-	O
+5	O
+in	O
+onchocerciasis	O
+:	O
+a	O
+critical	O
+role	O
+for	O
+IL	O
+-	O
+2	O
+.	O
+
+J	O
+Immuno11993	O
+;	O
+15	O
+{	O
+}	O
+;	O
+5511	O
+-	O
+5518	O
+.	O
+
+Yamaguchi	O
+Y	O
+,	O
+Matsui	O
+T	O
+,	O
+Kasahara	O
+T	O
+,	O
+et	O
+al	O
+.	O
+
+In	O
+vivo	O
+changes	O
+of	O
+hemapoietic	O
+progenitors	O
+and	O
+the	O
+expression	O
+of	O
+the	O
+interleukin	O
+gene	O
+in	O
+eosinophilic	O
+mice	B
+infected	O
+with	O
+Toxocara	B
+canis	I
+.	O
+
+Exp	O
+Hemato11990	O
+;	O
+18	O
+;	O
+1152	O
+-	O
+1157	O
+.	O
+
+Parsons	O
+JC	O
+,	O
+Coffman	O
+RL	O
+,	O
+Grieve	O
+RB	O
+.	O
+
+Antibody	O
+to	O
+interleukin	O
+prevents	O
+blood	O
+and	O
+tissue	O
+eosinophilia	O
+but	O
+not	O
+liver	O
+trapping	O
+in	O
+murine	B
+larval	O
+toxocariasis	O
+.	O
+
+Parasite	O
+Immuno11993	O
+;	O
+15	O
+:	O
+501	O
+-	O
+508	O
+.	O
+
+Coffman	O
+RL	O
+,	O
+Seymour	O
+BWP	O
+,	O
+Hudak	O
+S	O
+,	O
+Jackson	O
+J	O
+,	O
+Rennick	O
+D	O
+.	O
+Antibody	O
+to	O
+interleukin	O
+-	O
+5	O
+inhibits	O
+helminth	O
+-	O
+induced	O
+eosinophilia	O
+in	O
+mice	B
+.	O
+
+Science	O
+1989	O
+;	O
+245	O
+;	O
+308	O
+-	O
+310	O
+.	O
+
+Sher	O
+A	O
+,	O
+Coffman	O
+RL	O
+,	O
+Hieny	O
+S	O
+,	O
+Cheever	O
+AW	O
+.	O
+
+Ablation	O
+of	O
+eosinophil	O
+and	O
+IgE	O
+responses	O
+with	O
+anti	O
+-	O
+IL	O
+-	O
+5	O
+or	O
+anti	O
+-	O
+IL	O
+-	O
+4	O
+antibodies	O
+fails	O
+to	O
+affect	O
+immunity	O
+against	O
+Schistosoma	B
+mansoni	I
+in	O
+the	O
+mouse	B
+.	O
+
+J	O
+Immuno11990	O
+;	O
+145	O
+:	O
+3911	O
+
+26	O
+.	O
+
+27	O
+.	O
+
+ACKNOWLEDGEMENTS	O
+.	O
+
+This	O
+work	O
+was	O
+funded	O
+by	O
+grant	O
+300652	O
+/	O
+85	O
+-	O
+2	O
+from	O
+Conselho	O
+Nacional	O
+de	O
+Desenvolvimento	O
+Cientifico	O
+e	O
+Tecnol6gico	O
+(	O
+CNPq	O
+)	O
+and	O
+Grant	O
+92	O
+/	O
+5105	O
+-	O
+7	O
+from	O
+Fundago	O
+de	O
+Amparo	O
+ft	O
+Pesquisa	O
+do	O
+Estado	O
+de	O
+So	O
+Paulo	O
+(	O
+FAPESP	O
+)	O
+.	O
+
+We	O
+wish	O
+to	O
+thank	O
+Mrs	O
+M	O
+.	O
+A	O
+.	O
+
+Fernandes	O
+for	O
+technical	O
+assistance	O
+,	O
+Mrs	O
+M	O
+.	O
+M	O
+.	O
+O	O
+.	O
+
+Rossi	O
+for	O
+the	O
+histological	O
+sections	O
+,	O
+M	O
+.	O
+
+Costa	O
+Gongalves	O
+for	O
+the	O
+photography	O
+artwork	O
+,	O
+and	O
+Dr	O
+P	O
+.	O
+
+Minoprio	O
+,	O
+Institut	O
+Pasteur	O
+,	O
+for	O
+kindly	O
+providing	O
+TRFK	O
+-	O
+5	O
+.	O
+
+3916	O
+.	O
+
+10	O
+.	O
+
+Urban	O
+
+Jr	O
+JF	O
+,	O
+
+Katona	O
+IM	O
+,	O
+Paul	O
+WE	O
+,	O
+Finkelman	O
+FD	O
+.	O
+
+Interleukin	O
+4	O
+is	O
+impor	O
+
+Received	O
+12	O
+October	O
+1995	O
+;	O
+accepted	O
+17	O
+November	O
+1995	O
+
+Mediators	O
+of	O
+Inflammation	O
+Vol	O
+5	O
+
+1996	O
+
+31	O
+
+Modeling	O
+the	O
+effect	O
+of	O
+PTPN22	O
+in	O
+rheumatoid	O
+arthritis	O
+
+Abstract	O
+
+In	O
+order	O
+to	O
+model	O
+the	O
+effect	O
+of	O
+PTPN22	O
+on	O
+rheumatoid	O
+arthritis	O
+(	O
+RA	O
+)	O
+,	O
+we	O
+determined	O
+the	O
+combination	O
+of	O
+single	O
+-	O
+nucleotide	O
+-	O
+polymorphisms	O
+(	O
+SNPs	O
+)	O
+showing	O
+the	O
+strongest	O
+association	O
+with	O
+RA	O
+.	O
+
+Three	O
+SNPs	O
+(	O
+rs2476601	O
+-	O
+rs12730735	O
+-	O
+rs11102685	O
+)	O
+were	O
+selected	O
+for	O
+which	O
+we	O
+estimated	O
+the	O
+genotypic	O
+relative	O
+risks	O
+(	O
+GRRs	O
+)	O
+of	O
+the	O
+corresponding	O
+genotypes	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+these	O
+GRRs	O
+we	O
+defined	O
+four	O
+at	O
+-	O
+risk	O
+genotypic	O
+classes	O
+.	O
+
+Relative	O
+to	O
+the	O
+class	O
+of	O
+reference	O
+risk	O
+,	O
+individuals	O
+had	O
+a	O
+risk	O
+approximately	O
+multiplied	O
+by	O
+two	O
+,	O
+three	O
+,	O
+or	O
+four	O
+.	O
+
+This	O
+classification	O
+was	O
+confirmed	O
+by	O
+the	O
+excess	O
+of	O
+identity	O
+-	O
+by	O
+-	O
+descent	O
+(	O
+IBD	O
+)	O
+sharing	O
+(	O
+IBD	O
+=	O
+2	O
+)	O
+for	O
+the	O
+sibs	O
+of	O
+an	O
+index	O
+in	O
+the	O
+high	O
+-	O
+risk	O
+class	O
+and	O
+by	O
+excess	O
+of	O
+non	O
+-	O
+IBD	O
+sharing	O
+(	O
+IBD	O
+=	O
+0	O
+)	O
+when	O
+the	O
+index	O
+belonged	O
+to	O
+the	O
+low	O
+-	O
+risk	O
+class	O
+.	O
+
+The	O
+observed	O
+data	O
+could	O
+not	O
+be	O
+explained	O
+by	O
+the	O
+role	O
+of	O
+a	O
+single	O
+variant	O
+but	O
+were	O
+compatible	O
+either	O
+with	O
+a	O
+joint	O
+effect	O
+of	O
+the	O
+three	O
+typed	O
+SNPs	O
+of	O
+PTPN22	O
+on	O
+RA	O
+or	O
+with	O
+the	O
+role	O
+of	O
+two	O
+untyped	O
+variants	O
+.	O
+
+Background	O
+
+The	O
+single	O
+-	O
+nucleotide	O
+polymorphism	O
+(	O
+SNP	O
+)	O
+R620W	O
+,	O
+also	O
+denoted	O
+rs2476601	O
+,	O
+is	O
+located	O
+within	O
+the	O
+hematopoietic	O
+-	O
+specific	O
+protein	O
+tyrosine	O
+phosphatase	O
+gene	O
+,	O
+PTPN22	O
+.	O
+
+This	O
+SNP	O
+(	O
+C	O
+/	O
+T	O
+)	O
+codes	O
+for	O
+an	O
+amino	O
+-	O
+acid	O
+change	O
+and	O
+the	O
+frequency	O
+of	O
+its	O
+minor	O
+allele	O
+T	O
+has	O
+been	O
+recently	O
+and	O
+repeatedly	O
+shown	O
+to	O
+be	O
+increased	O
+in	O
+patients	B
+with	O
+rheumatoid	O
+arthritis	O
+(	O
+RA	O
+)	O
+[	O
+1	O
+]	O
+.	O
+
+The	O
+allele	O
+T	O
+confers	O
+1	O
+.	O
+7	O
+-	O
+to	O
+1	O
+.	O
+9	O
+-	O
+fold	O
+increased	O
+risk	O
+to	O
+heterozygote	O
+and	O
+higher	O
+risks	O
+to	O
+homozygote	O
+carriers	O
+[	O
+2	O
+]	O
+compared	O
+to	O
+the	O
+non	O
+-	O
+carrier	O
+individuals	O
+.	O
+
+This	O
+variant	O
+is	O
+also	O
+well	O
+known	O
+to	O
+be	O
+associated	O
+with	O
+several	O
+other	O
+autoimmune	O
+diseases	O
+[	O
+3	O
+]	O
+,	O
+such	O
+as	O
+systemic	O
+lupus	O
+erythematosus	O
+and	O
+type	O
+1	O
+diabetes	O
+.	O
+
+Recently	O
+,	O
+Carlton	O
+et	O
+al	O
+.	O
+
+[	O
+2	O
+]	O
+studied	O
+the	O
+PTPN22	O
+genetic	O
+variations	O
+in	O
+the	O
+North	O
+American	O
+Rheumatoid	O
+Arthritis	O
+Consortium	O
+(	O
+NARAC	O
+)	O
+data	O
+.	O
+
+Using	O
+the	O
+information	O
+on	O
+several	O
+SNPs	O
+typed	O
+in	O
+PTPN22	O
+,	O
+they	O
+compared	O
+the	O
+haplotype	O
+distributions	O
+in	O
+NARAC	O
+patients	B
+and	O
+controls	O
+.	O
+
+They	O
+demonstrated	O
+that	O
+SNP	O
+R620W	O
+does	O
+not	O
+fully	O
+explain	O
+the	O
+association	O
+between	O
+PTPN22	O
+and	O
+RA	O
+and	O
+suggested	O
+the	O
+effect	O
+of	O
+at	O
+least	O
+one	O
+additional	O
+variant	O
+in	O
+the	O
+PTPN22	O
+gene	O
+.	O
+
+We	O
+propose	O
+here	O
+to	O
+reanalyze	O
+the	O
+NARAC	O
+data	O
+using	O
+both	O
+association	O
+and	O
+linkage	O
+information	O
+for	O
+modeling	O
+the	O
+role	O
+of	O
+PTPN22	O
+in	O
+RA	O
+.	O
+
+Methods	O
+
+Data	O
+
+We	O
+selected	O
+from	O
+the	O
+NARAC	O
+data	O
+the	O
+511	O
+families	O
+with	O
+affected	O
+sib	O
+pairs	O
+typed	O
+for	O
+14	O
+SNPs	O
+of	O
+PTPN22	O
+,	O
+and	O
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+unrelated	O
+controls	O
+also	O
+typed	O
+for	O
+all	O
+these	O
+SNPs	O
+.	O
+
+For	O
+each	O
+affected	O
+sib	O
+pair	O
+we	O
+considered	O
+the	O
+proband	O
+as	O
+an	O
+index	O
+RA	O
+patient	B
+.	O
+
+The	O
+R620W	O
+SNP	O
+is	O
+one	O
+of	O
+the	O
+14	O
+SNPs	O
+in	O
+PTPN22	O
+.	O
+
+It	O
+is	O
+located	O
+at	O
+the	O
+ninth	O
+position	O
+,	O
+so	O
+it	O
+will	O
+be	O
+subsequently	O
+denoted	O
+as	O
+SNP	O
+9	O
+.	O
+
+A	O
+preliminary	O
+study	O
+of	O
+linkage	O
+disequilibrium	O
+(	O
+LD	O
+)	O
+among	O
+the	O
+14	O
+SNPs	O
+was	O
+examined	O
+in	O
+the	O
+1404	O
+controls	O
+.	O
+
+The	O
+LD	O
+analysis	O
+lead	O
+us	O
+to	O
+exclude	O
+3	O
+SNPs	O
+(	O
+SNP	O
+2	O
+,	O
+SNP	O
+12	O
+,	O
+SNP	O
+13	O
+)	O
+,	O
+which	O
+are	O
+in	O
+complete	O
+LD	O
+with	O
+one	O
+(	O
+or	O
+more	O
+)	O
+other	O
+SNP	O
+(	O
+s	O
+)	O
+.	O
+
+Selection	O
+of	O
+associated	O
+SNPs	O
+
+The	O
+combination	O
+test	O
+[	O
+4	O
+]	O
+was	O
+used	O
+on	O
+the	O
+11	O
+remaining	O
+SNPs	O
+to	O
+select	O
+the	O
+subset	O
+of	O
+SNPs	O
+showing	O
+a	O
+significant	O
+difference	O
+in	O
+the	O
+genotypic	O
+distribution	O
+between	O
+RA	O
+index	O
+patients	B
+and	O
+controls	O
+.	O
+
+Its	O
+principle	O
+consists	O
+in	O
+testing	O
+all	O
+possible	O
+combinations	O
+of	O
+SNPs	O
+within	O
+a	O
+gene	O
+.	O
+
+Here	O
+,	O
+there	O
+are	O
+(	O
+211	O
+-	O
+1	O
+)	O
+possible	O
+combinations	O
+.	O
+
+Such	O
+a	O
+systematic	O
+testing	O
+of	O
+all	O
+SNPs	O
+and	O
+all	O
+SNP	O
+combinations	O
+raises	O
+the	O
+problem	O
+of	O
+multiple	O
+and	O
+non	O
+-	O
+independent	O
+tests	O
+.	O
+
+This	O
+problem	O
+is	O
+generally	O
+solved	O
+by	O
+the	O
+implementation	O
+of	O
+a	O
+permutation	O
+procedure	O
+that	O
+allows	O
+estimation	O
+of	O
+corrected	O
+p	O
+-	O
+values	O
+.	O
+
+Here	O
+,	O
+associated	O
+combinations	O
+are	O
+very	O
+significant	O
+and	O
+the	O
+number	O
+of	O
+permutations	O
+necessary	O
+to	O
+discriminate	O
+them	O
+would	O
+be	O
+extremely	O
+high	O
+and	O
+almost	O
+unreachable	O
+.	O
+
+Nevertheless	O
+,	O
+the	O
+chi	O
+-	O
+square	O
+values	O
+of	O
+the	O
+genotypic	O
+association	O
+test	O
+are	O
+so	O
+high	O
+that	O
+even	O
+the	O
+conservative	O
+Bonferroni	O
+correction	O
+can	O
+be	O
+used	O
+.	O
+
+We	O
+selected	O
+the	O
+most	O
+associated	O
+and	O
+parsimonious	O
+subset	O
+of	O
+SNPs	O
+by	O
+nested	O
+chi	O
+-	O
+square	O
+tests	O
+(	O
+NCST	O
+)	O
+in	O
+a	O
+forward	O
+procedure	O
+.	O
+
+The	O
+NCST	O
+compares	O
+the	O
+strength	O
+of	O
+association	O
+between	O
+nested	O
+significant	O
+subsets	O
+.	O
+
+Genotypic	O
+relative	O
+-	O
+risk	O
+estimation	O
+
+For	O
+the	O
+selected	O
+subset	O
+of	O
+SNPs	O
+,	O
+we	O
+used	O
+the	O
+marker	O
+association	O
+segregation	O
+chi	O
+-	O
+square	O
+(	O
+MASC	O
+)	O
+method	O
+[	O
+5	O
+]	O
+to	O
+compute	O
+the	O
+genotypic	O
+relative	O
+risk	O
+(	O
+GRR	O
+)	O
+of	O
+each	O
+genotype	O
+.	O
+
+The	O
+genotype	O
+distributions	O
+of	O
+index	O
+and	O
+controls	O
+was	O
+conditional	O
+on	O
+the	O
+fact	O
+that	O
+the	O
+index	O
+has	O
+an	O
+affected	O
+sib	O
+.	O
+
+Stratified	O
+sib	O
+pair	O
+IBD	O
+estimation	O
+
+Conditional	O
+on	O
+each	O
+marker	O
+genotype	O
+of	O
+the	O
+index	O
+cases	O
+,	O
+the	O
+number	O
+of	O
+parental	O
+alleles	O
+identical	O
+by	O
+descent	O
+(	O
+IBD	O
+)	O
+shared	O
+by	O
+the	O
+index	O
+case	O
+and	O
+one	O
+affected	O
+sib	O
+were	O
+estimated	O
+on	O
+PTPN22	O
+with	O
+the	O
+MERLIN	O
+software	O
+[	O
+6	O
+]	O
+.	O
+
+MERLIN	O
+is	O
+able	O
+to	O
+take	O
+into	O
+account	O
+LD	O
+between	O
+SNPs	O
+during	O
+the	O
+IBD	O
+computation	O
+.	O
+
+So	O
+the	O
+estimated	O
+IBD	O
+distributions	O
+are	O
+computed	O
+on	O
+the	O
+overall	O
+set	O
+of	O
+SNPs	O
+even	O
+if	O
+they	O
+are	O
+in	O
+LD	O
+.	O
+
+The	O
+fit	O
+of	O
+a	O
+model	O
+to	O
+the	O
+IBD	O
+distributions	O
+stratified	O
+on	O
+index	O
+marker	O
+genotypes	O
+[	O
+7	O
+]	O
+may	O
+then	O
+be	O
+tested	O
+by	O
+the	O
+MASC	O
+method	O
+.	O
+
+Modeling	O
+PTPN22	O
+effect	O
+
+We	O
+applied	O
+the	O
+MASC	O
+method	O
+[	O
+5	O
+]	O
+to	O
+find	O
+the	O
+most	O
+parsimonious	O
+model	O
+explaining	O
+the	O
+overall	O
+observations	O
+,	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+genotype	O
+and	O
+the	O
+stratified	O
+sib	O
+-	O
+pair	O
+IBD	O
+distributions	O
+.	O
+
+To	O
+do	O
+this	O
+,	O
+MASC	O
+requires	O
+the	O
+haplotype	O
+frequencies	O
+in	O
+the	O
+general	O
+population	O
+,	O
+which	O
+were	O
+estimated	O
+on	O
+the	O
+unrelated	O
+controls	O
+by	O
+the	O
+MERLIN	O
+software	O
+.	O
+
+The	O
+MASC	O
+method	O
+computes	O
+the	O
+expected	O
+genotype	O
+marker	O
+distribution	O
+and	O
+the	O
+expected	O
+sib	O
+-	O
+pair	O
+IBD	O
+distributions	O
+stratified	O
+on	O
+marker	O
+genotypes	O
+for	O
+a	O
+given	O
+genetic	O
+model	O
+.	O
+
+Here	O
+,	O
+the	O
+computation	O
+of	O
+the	O
+genotypic	O
+distribution	O
+is	O
+conditioned	O
+on	O
+the	O
+fact	O
+that	O
+index	O
+cases	O
+have	O
+an	O
+affected	O
+sib	O
+.	O
+
+The	O
+global	O
+expected	O
+likelihood	O
+of	O
+the	O
+genetic	O
+model	O
+given	O
+the	O
+observed	O
+data	O
+is	O
+then	O
+computed	O
+as	O
+the	O
+product	O
+of	O
+the	O
+likelihoods	O
+of	O
+each	O
+expected	O
+distribution	O
+,	O
+and	O
+is	O
+maximized	O
+on	O
+the	O
+model	O
+parameters	O
+.	O
+
+The	O
+fit	O
+of	O
+the	O
+model	O
+to	O
+the	O
+observed	O
+data	O
+is	O
+tested	O
+by	O
+a	O
+likelihood	O
+ratio	O
+test	O
+(	O
+LRT	O
+)	O
+between	O
+global	O
+expected	O
+likelihood	O
+and	O
+the	O
+likelihood	O
+of	O
+the	O
+saturated	O
+model	O
+.	O
+
+Results	O
+
+Selection	O
+of	O
+associated	O
+SNPs	O
+
+Many	O
+subsets	O
+of	O
+SNPs	O
+show	O
+significant	O
+associations	O
+.	O
+
+Table	O
+1	O
+presents	O
+a	O
+selection	O
+of	O
+the	O
+most	O
+associated	O
+combinations	O
+of	O
+one	O
+,	O
+two	O
+,	O
+and	O
+three	O
+SNPs	O
+.	O
+
+When	O
+considering	O
+only	O
+the	O
+effect	O
+of	O
+a	O
+single	O
+SNP	O
+,	O
+the	O
+only	O
+significant	O
+associated	O
+one	O
+after	O
+correction	O
+for	O
+multiple	O
+testing	O
+is	O
+SNP	O
+9	O
+.	O
+
+The	O
+combination	O
+of	O
+SNPs	O
+9	O
+-	O
+10	O
+is	O
+the	O
+one	O
+which	O
+,	O
+among	O
+the	O
+combination	O
+of	O
+two	O
+SNPs	O
+,	O
+best	O
+improves	O
+the	O
+association	O
+shown	O
+by	O
+the	O
+SNP	O
+9	O
+alone	O
+(	O
+p	O
+=	O
+0	O
+.	O
+017	O
+)	O
+.	O
+
+The	O
+subset	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+(	O
+rs2476601	O
+-	O
+rs12730735	O
+-	O
+rs11102685	O
+)	O
+is	O
+the	O
+only	O
+one	O
+that	O
+improves	O
+significantly	O
+the	O
+association	O
+shown	O
+by	O
+the	O
+SNPs	O
+9	O
+-	O
+10	O
+(	O
+p	O
+=	O
+0	O
+.	O
+038	O
+)	O
+.	O
+
+Adding	O
+another	O
+SNP	O
+to	O
+this	O
+subset	O
+does	O
+not	O
+significantly	O
+improve	O
+the	O
+association	O
+.	O
+
+Consequently	O
+,	O
+all	O
+the	O
+subsequent	O
+analyses	O
+have	O
+been	O
+done	O
+considering	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+and	O
+their	O
+ten	O
+corresponding	O
+genotypes	O
+.	O
+
+GRR	O
+estimation	O
+
+Table	O
+2	O
+displays	O
+the	O
+genotypes	O
+and	O
+the	O
+corresponding	O
+GRRs	O
+for	O
+SNP	O
+9	O
+taken	O
+alone	O
+(	O
+columns	O
+1	O
+and	O
+2	O
+)	O
+and	O
+for	O
+the	O
+set	O
+of	O
+the	O
+three	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+(	O
+columns	O
+3	O
+and	O
+4	O
+)	O
+.	O
+
+The	O
+GRRs	O
+vary	O
+from	O
+1	O
+to	O
+2	O
+.	O
+7	O
+when	O
+considering	O
+only	O
+SNP	O
+9	O
+,	O
+whereas	O
+the	O
+variation	O
+ranges	O
+from	O
+1	O
+to	O
+4	O
+.	O
+7	O
+when	O
+the	O
+information	O
+on	O
+the	O
+three	O
+SNPs	O
+is	O
+taken	O
+into	O
+account	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+CC	O
+genotype	O
+of	O
+the	O
+SNP	O
+9	O
+can	O
+be	O
+subdivided	O
+in	O
+several	O
+genotypes	O
+when	O
+taking	O
+into	O
+account	O
+the	O
+genotypes	O
+for	O
+SNPs	O
+10	O
+and	O
+11	O
+(	O
+rows	O
+1	O
+to	O
+6	O
+)	O
+with	O
+GRRs	O
+ranging	O
+from	O
+1	O
+(	O
+CC	O
+-	O
+GG	O
+-	O
+AA	O
+)	O
+to	O
+3	O
+.	O
+6	O
+(	O
+CC	O
+-	O
+AA	O
+-	O
+GG	O
+)	O
+.	O
+
+This	O
+observation	O
+demonstrates	O
+the	O
+importance	O
+of	O
+using	O
+the	O
+additional	O
+information	O
+on	O
+SNPs	O
+10	O
+-	O
+11	O
+.	O
+
+Sib	O
+pair	O
+IBD	O
+estimation	O
+
+The	O
+proportion	O
+of	O
+RA	O
+sibs	O
+sharing	O
+0	O
+,	O
+1	O
+,	O
+or	O
+2	O
+parental	O
+alleles	O
+for	O
+PTPN22	O
+is	O
+0	O
+.	O
+26	O
+(	O
+181	O
+pairs	O
+)	O
+,	O
+0	O
+.	O
+51	O
+(	O
+362	O
+pairs	O
+)	O
+,	O
+and	O
+0	O
+.	O
+23	O
+(	O
+167	O
+pairs	O
+)	O
+,	O
+respectively	O
+,	O
+and	O
+does	O
+not	O
+differ	O
+from	O
+the	O
+IBD	O
+distribution	O
+0	O
+.	O
+25	O
+;	O
+0	O
+.	O
+5	O
+;	O
+0	O
+.	O
+25	O
+expected	O
+under	O
+no	O
+linkage	O
+.	O
+
+However	O
+,	O
+if	O
+our	O
+GRRs	O
+correctly	O
+reflect	O
+the	O
+differential	O
+risk	O
+of	O
+RA	O
+,	O
+we	O
+expect	O
+to	O
+see	O
+differences	O
+in	O
+the	O
+IBD	O
+vectors	O
+stratified	O
+on	O
+the	O
+genotypes	O
+of	O
+the	O
+subset	O
+of	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+[	O
+7	O
+]	O
+.	O
+
+To	O
+avoid	O
+cells	O
+with	O
+small	O
+numbers	O
+of	O
+individuals	O
+we	O
+pooled	O
+sib	O
+pairs	O
+with	O
+the	O
+index	O
+genotypes	O
+(	O
+SNP	O
+9	O
+-	O
+10	O
+-	O
+11	O
+)	O
+that	O
+have	O
+similar	O
+risk	O
+.	O
+
+We	O
+thus	O
+defined	O
+four	O
+arbitrary	O
+at	O
+risk	O
+genotypic	O
+classes	O
+:	O
+the	O
+low	O
+risk	O
+class	O
+(	O
+L	O
+;	O
+GRR	O
+=	O
+1	O
+;	O
+19	O
+pairs	O
+)	O
+,	O
+the	O
+intermediate	O
+risk	O
+class	O
+1	O
+(	O
+I1	O
+;	O
+1	O
+<	O
+GRR	O
+<	O
+=	O
+2	O
+;	O
+295	O
+pairs	O
+)	O
+,	O
+the	O
+intermediate	O
+risk	O
+class	O
+2	O
+(	O
+I2	O
+;	O
+2	O
+<	O
+GRR	O
+<	O
+=	O
+3	O
+;	O
+157	O
+pairs	O
+)	O
+,	O
+and	O
+the	O
+high	O
+risk	O
+class	O
+(	O
+H	O
+;	O
+GRR	O
+>	O
+3	O
+;	O
+34	O
+pairs	O
+)	O
+.	O
+
+Table	O
+3	O
+shows	O
+that	O
+the	O
+proportion	O
+of	O
+IBD	O
+=	O
+0	O
+decreases	O
+from	O
+0	O
+.	O
+47	O
+to	O
+0	O
+.	O
+09	O
+according	O
+to	O
+the	O
+fact	O
+that	O
+the	O
+index	O
+belongs	O
+to	O
+class	O
+L	O
+or	O
+class	O
+H	O
+and	O
+conversely	O
+,	O
+the	O
+proportion	O
+of	O
+IBD	O
+=	O
+2	O
+increases	O
+from	O
+0	O
+.	O
+11	O
+to	O
+0	O
+.	O
+26	O
+.	O
+
+These	O
+stratified	O
+IBD	O
+distributions	O
+are	O
+consistent	O
+with	O
+the	O
+risk	O
+genotypic	O
+classes	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+IBD	O
+sharing	O
+distributions	O
+stratified	O
+only	O
+on	O
+SNP	O
+9	O
+genotypes	O
+are	O
+not	O
+consistent	O
+with	O
+the	O
+GRR	O
+estimates	O
+on	O
+this	O
+SNP	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+Modeling	O
+PTPN22	O
+effect	O
+
+We	O
+apply	O
+the	O
+MASC	O
+method	O
+in	O
+using	O
+the	O
+genotype	O
+distribution	O
+only	O
+on	O
+the	O
+SNP	O
+9	O
+and	O
+the	O
+IBD	O
+stratified	O
+on	O
+the	O
+SNP	O
+9	O
+genotypes	O
+.	O
+
+In	O
+that	O
+case	O
+,	O
+the	O
+single	O
+and	O
+causal	O
+effect	O
+of	O
+the	O
+SNP	O
+9	O
+is	O
+not	O
+rejected	O
+(	O
+p	O
+=	O
+0	O
+.	O
+29	O
+)	O
+.	O
+
+Then	O
+,	O
+we	O
+model	O
+the	O
+effect	O
+of	O
+PTPN22	O
+using	O
+the	O
+four	O
+genotypic	O
+groups	O
+of	O
+risk	O
+defined	O
+on	O
+the	O
+genotypes	O
+of	O
+the	O
+combination	O
+of	O
+the	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+and	O
+the	O
+IBD	O
+information	O
+stratified	O
+on	O
+them	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+we	O
+reject	O
+the	O
+direct	O
+effect	O
+of	O
+SNP	O
+9	O
+(	O
+p	O
+=	O
+0	O
+.	O
+005	O
+)	O
+.	O
+
+We	O
+also	O
+reject	O
+the	O
+effect	O
+of	O
+a	O
+single	O
+untyped	O
+SNP	O
+(	O
+p	O
+=	O
+0	O
+.	O
+04	O
+)	O
+.	O
+
+However	O
+,	O
+we	O
+do	O
+not	O
+reject	O
+the	O
+interactive	O
+effect	O
+of	O
+the	O
+3	O
+SNPs	O
+(	O
+p	O
+=	O
+0	O
+.	O
+53	O
+)	O
+or	O
+the	O
+interactive	O
+effect	O
+of	O
+two	O
+untyped	O
+SNPs	O
+.	O
+
+Discussion	O
+
+The	O
+involvement	O
+of	O
+PTPN22	O
+and	O
+HLA	O
+in	O
+RA	O
+susceptibility	O
+is	O
+no	O
+longer	O
+disputed	O
+.	O
+
+However	O
+,	O
+as	O
+shown	O
+by	O
+Carlton	O
+et	O
+al	O
+.	O
+and	O
+confirmed	O
+in	O
+this	O
+study	O
+,	O
+the	O
+role	O
+of	O
+PTPN22	O
+cannot	O
+be	O
+explained	O
+only	O
+by	O
+the	O
+R620W	O
+SNP	O
+.	O
+
+A	O
+correct	O
+modeling	O
+of	O
+PTPN22	O
+is	O
+important	O
+and	O
+shows	O
+that	O
+the	O
+genotypic	O
+risk	O
+varies	O
+much	O
+more	O
+(	O
+1	O
+to	O
+4	O
+.	O
+7	O
+)	O
+than	O
+reported	O
+in	O
+the	O
+literature	O
+(	O
+1	O
+to	O
+2	O
+.	O
+7	O
+)	O
+[	O
+4	O
+]	O
+.	O
+
+In	O
+this	O
+study	O
+we	O
+proposed	O
+,	O
+for	O
+the	O
+first	O
+time	O
+,	O
+a	O
+model	O
+for	O
+the	O
+effect	O
+of	O
+PTPN22	O
+,	O
+taking	O
+into	O
+account	O
+both	O
+association	O
+and	O
+linkage	O
+information	O
+.	O
+
+Another	O
+method	O
+,	O
+called	O
+LAMP	O
+[	O
+8	O
+]	O
+was	O
+recently	O
+proposed	O
+for	O
+joint	O
+modeling	O
+of	O
+linkage	O
+and	O
+association	O
+[	O
+8	O
+]	O
+.	O
+
+The	O
+linkage	O
+information	O
+used	O
+by	O
+the	O
+LAMP	O
+method	O
+is	O
+the	O
+global	O
+IBD	O
+sharing	O
+of	O
+affected	O
+sib	O
+pairs	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+very	O
+important	O
+to	O
+note	O
+that	O
+the	O
+power	O
+of	O
+model	O
+discrimination	O
+strongly	O
+depends	O
+on	O
+the	O
+association	O
+and	O
+linkage	O
+information	O
+that	O
+is	O
+used	O
+.	O
+
+As	O
+shown	O
+here	O
+,	O
+the	O
+information	O
+on	O
+SNP	O
+9	O
+alone	O
+and	O
+on	O
+the	O
+global	O
+IBD	O
+is	O
+very	O
+poor	O
+as	O
+compared	O
+with	O
+that	O
+of	O
+the	O
+three	O
+SNPs	O
+9	O
+-	O
+10	O
+-	O
+11	O
+and	O
+to	O
+the	O
+stratified	O
+IBD	O
+distributions	O
+on	O
+the	O
+four	O
+at	O
+-	O
+risk	O
+genotype	O
+groups	O
+.	O
+
+In	O
+conclusion	O
+,	O
+we	O
+applied	O
+a	O
+four	O
+-	O
+step	O
+strategy	O
+to	O
+model	O
+the	O
+effect	O
+of	O
+a	O
+candidate	O
+gene	O
+covered	O
+by	O
+several	O
+SNPs	O
+:	O
+1	O
+)	O
+to	O
+select	O
+the	O
+most	O
+associated	O
+set	O
+of	O
+SNPs	O
+;	O
+2	O
+)	O
+to	O
+group	O
+the	O
+corresponding	O
+genotypes	O
+according	O
+their	O
+GRRs	O
+;	O
+3	O
+)	O
+to	O
+stratify	O
+IBD	O
+sharing	O
+information	O
+on	O
+the	O
+at	O
+-	O
+risk	O
+genotype	O
+groups	O
+;	O
+4	O
+)	O
+to	O
+model	O
+the	O
+effect	O
+of	O
+the	O
+candidate	O
+gene	O
+while	O
+taking	O
+into	O
+account	O
+both	O
+linkage	O
+and	O
+association	O
+information	O
+.	O
+
+This	O
+strategy	O
+allowed	O
+better	O
+modeling	O
+of	O
+the	O
+effect	O
+of	O
+PTPN22	O
+in	O
+RA	O
+susceptibility	O
+.	O
+
+Recently	O
+,	O
+du	O
+Montcel	O
+et	O
+al	O
+.	O
+
+[	O
+9	O
+]	O
+refined	O
+the	O
+modeling	O
+of	O
+HLA	O
+in	O
+RA	O
+susceptibility	O
+.	O
+
+A	O
+next	O
+step	O
+will	O
+be	O
+to	O
+use	O
+simultaneously	O
+the	O
+PTPN22	O
+and	O
+HLA	O
+information	O
+to	O
+evaluate	O
+their	O
+joint	O
+effects	O
+while	O
+taking	O
+into	O
+account	O
+important	O
+covariables	O
+such	O
+as	O
+age	O
+and	O
+gender	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Purinergic	O
+signalling	O
+in	O
+the	O
+subretinal	O
+space	O
+:	O
+a	O
+role	O
+in	O
+the	O
+communication	O
+between	O
+the	O
+retina	O
+and	O
+the	O
+RPE	O
+
+Abstract	O
+
+The	O
+retinal	O
+pigment	O
+epithelium	O
+(	O
+RPE	O
+)	O
+is	O
+separated	O
+from	O
+the	O
+photoreceptor	O
+outer	O
+segments	O
+by	O
+the	O
+subretinal	O
+space	O
+.	O
+
+While	O
+the	O
+actual	O
+volume	O
+of	O
+this	O
+space	O
+is	O
+minimal	O
+,	O
+the	O
+communication	O
+that	O
+occurs	O
+across	O
+this	O
+microenvironment	O
+is	O
+important	O
+to	O
+the	O
+visual	O
+process	O
+,	O
+and	O
+accumulating	O
+evidence	O
+suggests	O
+the	O
+purines	O
+ATP	O
+and	O
+adenosine	O
+contribute	O
+to	O
+this	O
+communication	O
+.	O
+
+P1	O
+and	O
+P2	O
+receptors	O
+are	O
+localized	O
+to	O
+membranes	O
+on	O
+both	O
+the	O
+photoreceptor	O
+outer	O
+segments	O
+and	O
+on	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+which	O
+border	O
+subretinal	O
+space	O
+.	O
+
+ATP	O
+is	O
+released	O
+across	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+into	O
+this	O
+space	O
+in	O
+response	O
+to	O
+various	O
+triggers	O
+including	O
+glutamate	O
+and	O
+chemical	O
+ischemia	O
+.	O
+
+This	O
+ATP	O
+is	O
+dephosphorylated	O
+into	O
+adenosine	O
+by	O
+a	O
+series	O
+of	O
+ectoenzymes	O
+on	O
+the	O
+RPE	O
+apical	O
+membrane	O
+.	O
+
+Regulation	O
+of	O
+release	O
+and	O
+ectoenzyme	O
+activity	O
+in	O
+response	O
+to	O
+light	O
+-	O
+sensitive	O
+signals	O
+can	O
+alter	O
+the	O
+balance	O
+of	O
+purines	O
+in	O
+subretinal	O
+space	O
+,	O
+and	O
+thus	O
+coordinate	O
+communication	O
+across	O
+subretinal	O
+space	O
+with	O
+the	O
+visual	O
+process	O
+.	O
+
+Introduction	O
+
+The	O
+retinal	O
+pigment	O
+epithelium	O
+(	O
+RPE	O
+)	O
+lies	O
+between	O
+the	O
+outer	O
+segments	O
+of	O
+the	O
+photoreceptors	O
+and	O
+the	O
+choroidal	O
+blood	O
+supply	O
+(	O
+Fig	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+RPE	O
+combines	O
+the	O
+functions	O
+of	O
+epithelial	O
+and	O
+glial	O
+cells	O
+,	O
+providing	O
+a	O
+barrier	O
+while	O
+also	O
+supporting	O
+the	O
+neural	O
+photoreceptors	O
+and	O
+modulating	O
+their	O
+function	O
+.	O
+
+Tight	O
+communication	O
+between	O
+photoreceptors	O
+and	O
+the	O
+RPE	O
+is	O
+critical	O
+to	O
+coordinate	O
+the	O
+multiple	O
+levels	O
+of	O
+interaction	O
+,	O
+and	O
+the	O
+purinergic	O
+contribution	O
+to	O
+this	O
+communication	O
+is	O
+becoming	O
+apparent	O
+.	O
+
+The	O
+relevance	O
+of	O
+this	O
+purinergic	O
+input	O
+is	O
+emphasized	O
+by	O
+the	O
+many	O
+functional	O
+effects	O
+of	O
+P1	O
+and	O
+P2	O
+receptor	O
+stimulation	O
+and	O
+by	O
+the	O
+multiple	O
+mechanisms	O
+in	O
+place	O
+to	O
+regulate	O
+subretinal	O
+levels	O
+of	O
+purine	O
+agonists	O
+.	O
+
+As	O
+the	O
+dynamics	O
+of	O
+ATP	O
+release	O
+and	O
+extracellular	O
+conversion	O
+into	O
+adenosine	O
+will	O
+modify	O
+agonist	O
+availability	O
+,	O
+the	O
+modulation	O
+of	O
+these	O
+processes	O
+can	O
+exert	O
+a	O
+temporal	O
+control	O
+on	O
+purinergic	O
+signaling	O
+.	O
+
+The	O
+following	O
+review	O
+will	O
+outline	O
+the	O
+main	O
+interactions	O
+between	O
+the	O
+RPE	O
+and	O
+photoreceptors	O
+,	O
+describe	O
+the	O
+effects	O
+of	O
+stimulating	O
+purinergic	O
+receptors	O
+on	O
+both	O
+sides	O
+of	O
+subretinal	O
+space	O
+,	O
+and	O
+summarize	O
+how	O
+levels	O
+of	O
+ATP	O
+,	O
+ADP	O
+,	O
+and	O
+adenosine	O
+are	O
+manipulated	O
+in	O
+this	O
+microenvironment	O
+.	O
+
+Fig	O
+.	O
+1Schematic	O
+illustration	O
+of	O
+the	O
+key	O
+components	O
+of	O
+purinergic	O
+signaling	O
+in	O
+the	O
+subretinal	O
+microenvironment	O
+.	O
+
+Stimulation	O
+of	O
+P2	O
+receptors	O
+on	O
+the	O
+RPE	O
+can	O
+enhance	O
+transepithelial	O
+fluid	O
+absorption	O
+while	O
+P1	O
+receptors	O
+can	O
+modulate	O
+phagocytosis	O
+.	O
+
+ATP	O
+released	O
+through	O
+CFTR	O
+and	O
+other	O
+Cl	O
+-	O
+channels	O
+can	O
+stimulate	O
+P2	O
+receptors	O
+or	O
+be	O
+converted	O
+to	O
+ADP	O
+,	O
+AMP	O
+,	O
+and	O
+adenosine	O
+(	O
+Ado	O
+)	O
+by	O
+a	O
+series	O
+of	O
+ectonucleotidases	O
+present	O
+on	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+.	O
+
+By	O
+controlling	O
+the	O
+balance	O
+of	O
+extracellular	O
+purines	O
+available	O
+to	O
+stimulate	O
+these	O
+receptors	O
+these	O
+mechanisms	O
+can	O
+control	O
+levels	O
+of	O
+endogenous	O
+purines	O
+available	O
+to	O
+activate	O
+the	O
+receptors	O
+.	O
+
+While	O
+theoretically	O
+possible	O
+,	O
+it	O
+remains	O
+to	O
+be	O
+determined	O
+whether	O
+these	O
+subretinal	O
+purines	O
+can	O
+actually	O
+stimulate	O
+photoreceptors	O
+
+Purines	O
+and	O
+subretinal	O
+space	O
+
+RPE	O
+-	O
+photoreceptor	O
+interactions	O
+across	O
+the	O
+subretinal	O
+space	O
+
+The	O
+outer	O
+segments	O
+of	O
+the	O
+rods	O
+and	O
+cones	O
+are	O
+responsible	O
+for	O
+the	O
+initial	O
+stages	O
+of	O
+vision	O
+,	O
+converting	O
+photon	O
+energy	O
+into	O
+a	O
+series	O
+of	O
+enzymatic	O
+reactions	O
+that	O
+close	O
+the	O
+light	O
+-	O
+sensitive	O
+channels	O
+on	O
+the	O
+photoreceptor	O
+plasma	O
+membrane	O
+,	O
+hyperpolarize	O
+the	O
+cells	O
+,	O
+and	O
+reduce	O
+the	O
+release	O
+of	O
+glutamate	O
+from	O
+the	O
+synaptic	O
+terminals	O
+[	O
+1	O
+,	O
+2	O
+]	O
+.	O
+
+Efficient	O
+photoreceptor	O
+function	O
+depends	O
+upon	O
+both	O
+short	O
+-	O
+term	O
+and	O
+long	O
+-	O
+term	O
+support	O
+from	O
+the	O
+RPE	O
+.	O
+
+The	O
+critical	O
+nature	O
+of	O
+these	O
+interactions	O
+is	O
+evident	O
+from	O
+the	O
+rapid	O
+degeneration	O
+of	O
+photoreceptors	O
+in	O
+the	O
+absence	O
+of	O
+a	O
+healthy	O
+RPE	O
+layer	O
+and	O
+by	O
+the	O
+RPE	O
+localization	O
+of	O
+defective	O
+gene	O
+product	O
+in	O
+some	O
+forms	O
+of	O
+hereditary	O
+photoreceptor	O
+degeneration	O
+[	O
+3	O
+]	O
+.	O
+
+The	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+is	O
+separated	O
+from	O
+the	O
+plasma	O
+membrane	O
+of	O
+the	O
+outer	O
+segments	O
+by	O
+an	O
+extracellular	O
+space	O
+of	O
+only	O
+10	O
+-	O
+20	O
+nm	O
+[	O
+4	O
+]	O
+.	O
+
+Although	O
+small	O
+,	O
+this	O
+subretinal	O
+space	O
+contains	O
+a	O
+highly	O
+structured	O
+matrix	O
+which	O
+ensheathes	O
+the	O
+outer	O
+segments	O
+and	O
+extends	O
+to	O
+the	O
+RPE	O
+[	O
+5	O
+,	O
+6	O
+]	O
+.	O
+
+The	O
+presence	O
+of	O
+enzymes	O
+within	O
+this	O
+interphotoreceptor	O
+matrix	O
+emphasizes	O
+that	O
+this	O
+extracellular	O
+space	O
+itself	O
+is	O
+functionally	O
+active	O
+[	O
+7	O
+,	O
+8	O
+]	O
+.	O
+
+This	O
+intimate	O
+anatomical	O
+relationship	O
+between	O
+photoreceptors	O
+and	O
+the	O
+RPE	O
+reflects	O
+multiple	O
+functional	O
+interactions	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+RPE	O
+accepts	O
+,	O
+recycles	O
+,	O
+and	O
+exports	O
+central	O
+components	O
+of	O
+the	O
+phototransduction	O
+process	O
+[	O
+9	O
+]	O
+.	O
+
+The	O
+outer	O
+segments	O
+are	O
+continuously	O
+resynthesized	O
+,	O
+and	O
+the	O
+phagocytosis	O
+,	O
+degradation	O
+,	O
+and	O
+processing	O
+of	O
+shed	O
+outer	O
+segment	O
+tips	O
+by	O
+the	O
+RPE	O
+cells	O
+is	O
+central	O
+to	O
+this	O
+renewal	O
+[	O
+10	O
+]	O
+.	O
+
+The	O
+ion	O
+channels	O
+and	O
+transporters	O
+on	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+help	O
+regulate	O
+the	O
+ionic	O
+composition	O
+of	O
+the	O
+subretinal	O
+space	O
+[	O
+11	O
+]	O
+.	O
+
+As	O
+extracellular	O
+levels	O
+of	O
+ions	O
+can	O
+modify	O
+the	O
+ionic	O
+driving	O
+forces	O
+across	O
+the	O
+photoreceptor	O
+plasma	O
+membrane	O
+,	O
+these	O
+RPE	O
+transporters	O
+can	O
+influence	O
+the	O
+state	O
+of	O
+neural	O
+activity	O
+.	O
+
+The	O
+transport	O
+of	O
+fluid	O
+and	O
+ions	O
+from	O
+the	O
+apical	O
+membrane	O
+to	O
+basolateral	O
+membrane	O
+of	O
+the	O
+RPE	O
+is	O
+also	O
+one	O
+of	O
+the	O
+main	O
+forces	O
+keeping	O
+the	O
+retina	O
+attached	O
+[	O
+12	O
+]	O
+.	O
+
+The	O
+control	O
+of	O
+photoreceptor	O
+activity	O
+by	O
+light	O
+gives	O
+a	O
+rapid	O
+temporal	O
+dependence	O
+to	O
+some	O
+interactions	O
+between	O
+the	O
+photoreceptors	O
+and	O
+the	O
+RPE	O
+.	O
+
+The	O
+volume	O
+of	O
+subretinal	O
+space	O
+increases	O
+in	O
+response	O
+to	O
+light	O
+[	O
+13	O
+]	O
+,	O
+linking	O
+small	O
+changes	O
+in	O
+the	O
+ionic	O
+composition	O
+of	O
+the	O
+subretinal	O
+space	O
+with	O
+activity	O
+of	O
+the	O
+RPE	O
+transport	O
+mechanisms	O
+which	O
+maintain	O
+this	O
+volume	O
+[	O
+14	O
+,	O
+15	O
+]	O
+.	O
+
+Other	O
+processes	O
+are	O
+controlled	O
+on	O
+a	O
+diurnal	O
+cycle	O
+.	O
+
+The	O
+shed	O
+tips	O
+of	O
+the	O
+outer	O
+segments	O
+are	O
+phagocytosed	O
+by	O
+the	O
+RPE	O
+soon	O
+after	O
+the	O
+onset	O
+of	O
+light	O
+[	O
+16	O
+,	O
+17	O
+]	O
+.	O
+
+These	O
+processes	O
+can	O
+both	O
+be	O
+modulated	O
+by	O
+purine	O
+levels	O
+in	O
+subretinal	O
+space	O
+,	O
+indicating	O
+purinergic	O
+regulation	O
+is	O
+important	O
+over	O
+multiple	O
+time	O
+scales	O
+.	O
+
+Purinergic	O
+receptors	O
+on	O
+photoreceptors	O
+
+A2	O
+adenosine	O
+receptors	O
+were	O
+localized	O
+to	O
+both	O
+the	O
+inner	O
+and	O
+outer	O
+segments	O
+of	O
+photoreceptor	O
+outer	O
+segments	O
+over	O
+a	O
+decade	O
+ago	O
+by	O
+Blazynski	O
+and	O
+colleagues	O
+[	O
+18	O
+]	O
+,	O
+with	O
+more	O
+recent	O
+reports	O
+emphasizing	O
+their	O
+functional	O
+role	O
+.	O
+
+A2	O
+agonists	O
+inhibit	O
+the	O
+L	O
+-	O
+type	O
+Ca2	O
++	O
+channel	O
+on	O
+rod	O
+outer	O
+segments	O
+[	O
+19	O
+]	O
+and	O
+can	O
+inhibit	O
+the	O
+synaptic	O
+release	O
+of	O
+glutamate	O
+from	O
+rods	O
+,	O
+suggesting	O
+changes	O
+in	O
+adenosine	O
+levels	O
+in	O
+subretinal	O
+space	O
+could	O
+modulate	O
+light	O
+sensitivity	O
+[	O
+20	O
+]	O
+.	O
+
+The	O
+A2	O
+agonist	O
+DPMA	O
+and	O
+the	O
+adenosine	O
+deaminase	O
+inhibitor	O
+EHNA	O
+reduce	O
+mRNA	O
+for	O
+opsin	O
+in	O
+rods	O
+,	O
+suggesting	O
+that	O
+endogenous	O
+levels	O
+of	O
+adenosine	O
+can	O
+downregulate	O
+opsin	O
+message	O
+at	O
+night	O
+[	O
+21	O
+]	O
+.	O
+
+EHNA	O
+and	O
+the	O
+A2A	O
+receptor	O
+agonist	O
+CGS21680	O
+also	O
+increase	O
+the	O
+survival	O
+of	O
+chick	O
+embryonic	O
+photoreceptors	O
+in	O
+culture	O
+[	O
+22	O
+]	O
+,	O
+indicating	O
+a	O
+long	O
+-	O
+term	O
+neuroprotective	O
+role	O
+for	O
+adenosine	O
+.	O
+
+P2	O
+receptors	O
+are	O
+also	O
+present	O
+in	O
+the	O
+photoreceptors	O
+.	O
+
+mRNA	O
+for	O
+the	O
+P2X2	O
+receptor	O
+is	O
+expressed	O
+in	O
+the	O
+photoreceptor	O
+cell	O
+bodies	O
+,	O
+with	O
+immunohistochemical	O
+localization	O
+of	O
+the	O
+protein	O
+to	O
+outer	O
+segments	O
+[	O
+23	O
+]	O
+.	O
+
+In	O
+situ	O
+hybridization	O
+indicates	O
+the	O
+photoreceptor	O
+layer	O
+has	O
+the	O
+highest	O
+level	O
+of	O
+P2Y2	O
+receptor	O
+of	O
+any	O
+region	O
+in	O
+the	O
+rabbit	B
+retina	O
+,	O
+although	O
+staining	O
+was	O
+not	O
+pronounced	O
+in	O
+monkey	O
+[	O
+24	O
+]	O
+.	O
+
+P2X7	O
+receptors	O
+have	O
+recently	O
+been	O
+localized	O
+to	O
+photoreceptor	O
+synaptic	O
+terminals	O
+,	O
+with	O
+evidence	O
+for	O
+ecto	O
+-	O
+ATPase	O
+activity	O
+in	O
+the	O
+synapse	O
+,	O
+and	O
+functional	O
+evidence	O
+suggesting	O
+ATP	O
+augments	O
+transmission	O
+of	O
+the	O
+light	O
+response	O
+by	O
+rods	O
+[	O
+25	O
+]	O
+.	O
+
+It	O
+was	O
+suggested	O
+that	O
+ATP	O
+might	O
+be	O
+co	O
+-	O
+released	O
+from	O
+photoreceptors	O
+with	O
+glutamate	O
+,	O
+although	O
+this	O
+remains	O
+to	O
+be	O
+tested	O
+directly	O
+.	O
+
+Purinergic	O
+receptors	O
+on	O
+the	O
+RPE	O
+
+Stimulation	O
+of	O
+P1	O
+receptors	O
+can	O
+have	O
+a	O
+considerable	O
+impact	O
+on	O
+RPE	O
+cells	O
+.	O
+
+A2	O
+receptors	O
+have	O
+been	O
+recognized	O
+on	O
+cultured	O
+and	O
+fresh	O
+RPE	O
+cells	O
+for	O
+some	O
+time	O
+[	O
+26	O
+,	O
+27	O
+]	O
+,	O
+with	O
+in	O
+situ	O
+hybridization	O
+confirming	O
+the	O
+presence	O
+of	O
+A2A	O
+receptors	O
+in	O
+rat	B
+RPE	O
+[	O
+28	O
+]	O
+.	O
+
+Stimulation	O
+of	O
+A2	O
+receptors	O
+reduces	O
+the	O
+rate	O
+of	O
+rod	O
+outer	O
+segment	O
+phagocytosis	O
+by	O
+RPE	O
+cells	O
+[	O
+29	O
+]	O
+,	O
+while	O
+application	O
+of	O
+adenosine	O
+to	O
+the	O
+apical	O
+membrane	O
+of	O
+chick	O
+RPE	O
+cells	O
+increases	O
+the	O
+basolateral	O
+Cl	O
+-	O
+conductance	O
+,	O
+the	O
+transepithelial	O
+potential	O
+,	O
+and	O
+the	O
+c	O
+-	O
+wave	O
+,	O
+and	O
+decreases	O
+the	O
+hyperpolarization	O
+of	O
+the	O
+basal	O
+membrane	O
+in	O
+response	O
+to	O
+light	O
+[	O
+30	O
+]	O
+.	O
+
+Although	O
+adenosine	O
+alone	O
+does	O
+not	O
+increase	O
+intracellular	O
+Ca2	O
++	O
+levels	O
+[	O
+31	O
+]	O
+,	O
+adenosine	O
+acts	O
+synergistically	O
+with	O
+ATP	O
+to	O
+elevate	O
+Ca2	O
++	O
+levels	O
+in	O
+human	B
+RPE	O
+cells	O
+by	O
+stimulating	O
+both	O
+A1	O
+and	O
+A2A	O
+receptors	O
+[	O
+32	O
+,	O
+33	O
+]	O
+.	O
+
+Stimulation	O
+of	O
+A1	O
+receptors	O
+with	O
+high	O
+doses	O
+of	O
+NECA	O
+increases	O
+the	O
+active	O
+transport	O
+of	O
+fluorescein	O
+across	O
+the	O
+RPE	O
+,	O
+while	O
+activation	O
+of	O
+A2A	O
+receptors	O
+decreases	O
+this	O
+transport	O
+,	O
+and	O
+by	O
+extension	O
+,	O
+transport	O
+of	O
+the	O
+ions	O
+that	O
+underlie	O
+fluid	O
+movement	O
+[	O
+34	O
+]	O
+.	O
+
+Stimulation	O
+of	O
+A1	O
+and	O
+A2A	O
+receptors	O
+produces	O
+analogous	O
+increases	O
+and	O
+decreases	O
+,	O
+respectively	O
+,	O
+in	O
+the	O
+absorption	O
+of	O
+subretinal	O
+fluid	O
+blebs	O
+.	O
+
+This	O
+is	O
+consistent	O
+with	O
+the	O
+negative	O
+coupling	O
+of	O
+the	O
+A1	O
+receptor	O
+and	O
+the	O
+positive	O
+coupling	O
+of	O
+the	O
+A2	O
+receptors	O
+to	O
+adenylate	O
+cyclase	O
+,	O
+as	O
+increasing	O
+cAMP	O
+inhibits	O
+the	O
+transport	O
+of	O
+fluid	O
+across	O
+the	O
+RPE	O
+towards	O
+the	O
+choroid	O
+[	O
+35	O
+-	O
+37	O
+]	O
+.	O
+
+The	O
+agonist	O
+2	O
+-	O
+Cl	O
+adenosine	O
+reverses	O
+the	O
+deficit	O
+in	O
+phosphoinositide	O
+metabolism	O
+found	O
+in	O
+diabetic	O
+RPE	O
+cells	O
+[	O
+38	O
+]	O
+,	O
+suggesting	O
+effects	O
+on	O
+metabolism	O
+in	O
+addition	O
+to	O
+transport	O
+and	O
+phagocytosis	O
+.	O
+
+Multiple	O
+P2	O
+receptors	O
+have	O
+been	O
+localized	O
+to	O
+the	O
+RPE	O
+.	O
+
+The	O
+P2Y2	O
+receptor	O
+was	O
+initially	O
+characterized	O
+in	O
+cultured	O
+human	B
+RPE	O
+[	O
+31	O
+]	O
+,	O
+with	O
+subsequent	O
+reports	O
+localizing	O
+transcript	O
+for	O
+P2Y1	O
+,	O
+P2Y2	O
+,	O
+P2Y4	O
+,	O
+and	O
+P2Y6	O
+in	O
+the	O
+rat	B
+RPE	O
+/	O
+choroid	O
+[	O
+39	O
+]	O
+and	O
+for	O
+P2Y1	O
+and	O
+P2Y12	O
+receptors	O
+in	O
+ARPE	O
+-	O
+19	O
+cells	O
+[	O
+40	O
+]	O
+,	O
+and	O
+functionally	O
+identifying	O
+a	O
+P2X	O
+receptor	O
+in	O
+rat	B
+RPE	O
+cells	O
+[	O
+41	O
+]	O
+.	O
+
+ATP	O
+,	O
+ADP	O
+,	O
+and	O
+UTP	O
+induce	O
+numerous	O
+effects	O
+on	O
+RPE	O
+physiology	O
+[	O
+32	O
+,	O
+33	O
+,	O
+42	O
+,	O
+43	O
+]	O
+.	O
+
+While	O
+these	O
+effects	O
+likely	O
+involve	O
+multiple	O
+different	O
+receptor	O
+types	O
+,	O
+the	O
+contributions	O
+of	O
+the	O
+P2Y2	O
+receptor	O
+have	O
+been	O
+explored	O
+in	O
+most	O
+detail	O
+to	O
+date	O
+.	O
+
+The	O
+P2Y2	O
+receptor	O
+has	O
+been	O
+specifically	O
+localized	O
+to	O
+the	O
+apical	O
+membrane	O
+of	O
+fresh	O
+bovine	B
+RPE	O
+cells	O
+,	O
+and	O
+addition	O
+of	O
+ATP	O
+to	O
+this	O
+membrane	O
+transiently	O
+elevates	O
+Ca2	O
++	O
+,	O
+activates	O
+a	O
+basolateral	O
+Cl	O
+-	O
+conductance	O
+,	O
+inhibits	O
+an	O
+apical	O
+K	O
++	O
+conductance	O
+,	O
+and	O
+increases	O
+the	O
+apical	O
+to	O
+basolateral	O
+flow	O
+of	O
+fluid	O
+[	O
+43	O
+]	O
+.	O
+
+This	O
+increased	O
+absorption	O
+of	O
+fluid	O
+from	O
+the	O
+subretinal	O
+space	O
+suggests	O
+P2Y2	O
+receptor	O
+stimulation	O
+could	O
+reduce	O
+the	O
+excess	O
+fluid	O
+that	O
+accumulates	O
+in	O
+retinal	O
+edemas	O
+,	O
+and	O
+several	O
+reports	O
+have	O
+supported	O
+this	O
+theory	O
+.	O
+
+ATP	O
+,	O
+UTP	O
+,	O
+and	O
+the	O
+P2Y2	O
+receptor	O
+agonist	O
+INS37217	O
+decrease	O
+the	O
+size	O
+of	O
+subretinal	O
+fluid	O
+blebs	O
+when	O
+injected	O
+into	O
+subretinal	O
+space	O
+of	O
+rats	B
+[	O
+44	O
+]	O
+.	O
+
+In	O
+both	O
+normal	O
+and	O
+rds	O
++	O
+/	O
+-	O
+mice	B
+with	O
+experimentally	O
+induced	O
+detachment	O
+,	O
+INS31217	O
+improves	O
+the	O
+ERG	O
+recovery	O
+and	O
+decreased	O
+cell	O
+death	O
+[	O
+45	O
+]	O
+.	O
+
+INS37217	O
+also	O
+reduces	O
+subretinal	O
+blebs	O
+in	O
+rabbits	B
+[	O
+46	O
+]	O
+.	O
+
+Injection	O
+of	O
+another	O
+P2Y2	O
+agonist	O
+,	O
+INS542	O
+,	O
+increases	O
+the	O
+active	O
+transport	O
+of	O
+fluorescein	O
+across	O
+the	O
+RPE	O
+,	O
+consistent	O
+with	O
+this	O
+upregulation	O
+of	O
+ion	O
+and	O
+fluid	O
+transport	O
+across	O
+the	O
+tissue	O
+[	O
+47	O
+]	O
+.	O
+
+Together	O
+these	O
+experiments	O
+emphasize	O
+the	O
+clinical	O
+potential	O
+of	O
+treating	O
+retinal	O
+edema	O
+with	O
+P2Y2	O
+agonists	O
+.	O
+
+Regulation	O
+of	O
+purine	O
+levels	O
+in	O
+subretinal	O
+space	O
+
+While	O
+synthesized	O
+purinergic	O
+agonists	O
+may	O
+prove	O
+useful	O
+in	O
+treating	O
+some	O
+ocular	O
+disorders	O
+,	O
+the	O
+endogenous	O
+activation	O
+of	O
+P1	O
+and	O
+P2	O
+receptors	O
+in	O
+the	O
+subretinal	O
+microenvironment	O
+will	O
+ultimately	O
+be	O
+determined	O
+by	O
+availability	O
+of	O
+agonists	O
+.	O
+
+These	O
+levels	O
+are	O
+largely	O
+controlled	O
+by	O
+the	O
+release	O
+of	O
+ATP	O
+into	O
+the	O
+subretinal	O
+space	O
+,	O
+its	O
+conversion	O
+into	O
+other	O
+purines	O
+including	O
+adenosine	O
+,	O
+and	O
+the	O
+manipulation	O
+of	O
+adenosine	O
+by	O
+enzymes	O
+or	O
+transporters	O
+.	O
+
+Recent	O
+work	O
+has	O
+increased	O
+our	O
+understanding	O
+of	O
+both	O
+the	O
+stimuli	O
+that	O
+initiate	O
+changes	O
+in	O
+subretinal	O
+purine	O
+levels	O
+and	O
+the	O
+mechanisms	O
+that	O
+mediate	O
+these	O
+changes	O
+.	O
+
+Release	O
+of	O
+ATP	O
+by	O
+the	O
+RPE	O
+
+At	O
+least	O
+some	O
+of	O
+the	O
+ATP	O
+capable	O
+of	O
+stimulating	O
+the	O
+purinergic	O
+receptors	O
+on	O
+RPE	O
+cells	O
+is	O
+released	O
+from	O
+the	O
+RPE	O
+itself	O
+.	O
+
+The	O
+resulting	O
+autocrine	O
+stimulation	O
+ensures	O
+local	O
+delivery	O
+,	O
+and	O
+control	O
+,	O
+of	O
+purines	O
+to	O
+initiate	O
+the	O
+physiologic	O
+changes	O
+in	O
+the	O
+RPE	O
+.	O
+
+The	O
+release	O
+of	O
+ATP	O
+by	O
+RPE	O
+cells	O
+is	O
+triggered	O
+by	O
+multiple	O
+stimuli	O
+including	O
+osmotic	O
+stress	O
+,	O
+bFGF	O
+,	O
+UTP	O
+,	O
+NMDA	O
+,	O
+glutamate	O
+,	O
+and	O
+ATP	O
+[	O
+39	O
+,	O
+40	O
+,	O
+48	O
+-	O
+51	O
+]	O
+.	O
+
+The	O
+ATP	O
+release	O
+following	O
+activation	O
+of	O
+NMDA	O
+receptors	O
+by	O
+glutamate	O
+may	O
+have	O
+the	O
+most	O
+interesting	O
+implications	O
+for	O
+communication	O
+across	O
+subretinal	O
+space	O
+,	O
+given	O
+that	O
+glutamate	O
+confers	O
+the	O
+light	O
+signal	O
+from	O
+photoreceptors	O
+to	O
+the	O
+rest	O
+of	O
+the	O
+visual	O
+system	O
+.	O
+
+Glutamate	O
+and	O
+the	O
+specific	O
+receptor	O
+agonist	O
+NMDA	O
+triggers	O
+ATP	O
+release	O
+from	O
+ARPE	O
+-	O
+19	O
+cells	O
+,	O
+with	O
+the	O
+release	O
+inhibited	O
+by	O
+NMDA	O
+antagonist	O
+MK	O
+-	O
+801	O
+,	O
+and	O
+by	O
+DCKA	O
+,	O
+which	O
+inhibits	O
+the	O
+glycine	O
+B	O
+binding	O
+site	O
+on	O
+NMDA	O
+receptors	O
+[	O
+51	O
+,	O
+52	O
+]	O
+.	O
+
+Although	O
+NMDA	O
+raises	O
+intracellular	O
+Ca2	O
++	O
+levels	O
+,	O
+this	O
+increase	O
+is	O
+prevented	O
+by	O
+eliminating	O
+ATP	O
+with	O
+apyrase	O
+,	O
+indicating	O
+autostimulation	O
+through	O
+released	O
+ATP	O
+is	O
+responsible	O
+for	O
+this	O
+Ca2	O
++	O
+signal	O
+.	O
+
+NMDA	O
+also	O
+triggers	O
+a	O
+release	O
+of	O
+ATP	O
+when	O
+applied	O
+to	O
+the	O
+intact	O
+bovine	B
+RPE	O
+eyecup	O
+[	O
+51	O
+]	O
+.	O
+
+The	O
+NMDA	O
+receptors	O
+and	O
+the	O
+ATP	O
+release	O
+sites	O
+have	O
+been	O
+functionally	O
+identified	O
+to	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+bovine	B
+RPE	O
+,	O
+suggesting	O
+the	O
+neurotransmitter	O
+interactions	O
+could	O
+amplify	O
+the	O
+signal	O
+from	O
+any	O
+glutamate	O
+reaching	O
+subretinal	O
+space	O
+.	O
+
+The	O
+ability	O
+of	O
+both	O
+UTP	O
+and	O
+ATP	O
+to	O
+stimulate	O
+release	O
+of	O
+ATP	O
+from	O
+the	O
+RPE	O
+supports	O
+the	O
+theory	O
+that	O
+the	O
+system	O
+acts	O
+to	O
+amplify	O
+signals	O
+.	O
+
+When	O
+applied	O
+at	O
+greater	O
+than	O
+1	O
+mu	O
+M	O
+,	O
+ATP	O
+triggers	O
+a	O
+secondary	O
+release	O
+of	O
+ATP	O
+peaking	O
+10	O
+min	O
+after	O
+the	O
+initial	O
+stimuli	O
+[	O
+40	O
+]	O
+.	O
+
+UTP	O
+also	O
+initiates	O
+a	O
+release	O
+in	O
+extracellular	O
+ATP	O
+with	O
+a	O
+similar	O
+delay	O
+[	O
+48	O
+]	O
+.	O
+
+The	O
+rise	O
+in	O
+ATP	O
+triggered	O
+by	O
+UTP	O
+is	O
+inhibited	O
+by	O
+the	O
+Cl	O
+-	O
+channel	O
+blocker	O
+NPPB	O
+,	O
+and	O
+UDP	O
+is	O
+much	O
+less	O
+effective	O
+at	O
+triggering	O
+release	O
+than	O
+UTP	O
+;	O
+both	O
+observations	O
+suggest	O
+the	O
+P2Y2	O
+receptor	O
+contributes	O
+to	O
+the	O
+increase	O
+in	O
+ATP	O
+more	O
+than	O
+diphosphokinase	O
+,	O
+although	O
+influence	O
+from	O
+the	O
+enzyme	O
+cannot	O
+be	O
+ruled	O
+out	O
+[	O
+53	O
+]	O
+.	O
+
+Recent	O
+evidence	O
+suggests	O
+that	O
+ischemia	O
+may	O
+lead	O
+to	O
+the	O
+release	O
+of	O
+ATP	O
+from	O
+RPE	O
+cells	O
+.	O
+
+Chemical	O
+ischemia	O
+triggers	O
+a	O
+substantial	O
+ATP	O
+release	O
+from	O
+cardiac	O
+myocytes	O
+[	O
+54	O
+]	O
+,	O
+while	O
+changes	O
+in	O
+oxygen	O
+levels	O
+trigger	O
+ATP	O
+release	O
+in	O
+central	O
+chemoreceptors	O
+[	O
+55	O
+]	O
+.	O
+
+We	O
+found	O
+that	O
+exposure	O
+to	O
+sodium	O
+cyanide	O
+led	O
+to	O
+a	O
+rapid	O
+release	O
+of	O
+ATP	O
+from	O
+ARPE	O
+-	O
+19	O
+cells	O
+(	O
+Fig	O
+.	O
+2	O
+)	O
+.	O
+
+As	O
+hypoxic	O
+and	O
+/	O
+or	O
+ischemic	O
+challenge	O
+may	O
+lead	O
+to	O
+changes	O
+in	O
+the	O
+expression	O
+of	O
+growth	O
+factors	O
+in	O
+RPE	O
+cells	O
+during	O
+certain	O
+ocular	O
+disorders	O
+such	O
+as	O
+macular	O
+degeneration	O
+[	O
+56	O
+]	O
+,	O
+and	O
+as	O
+purines	O
+can	O
+induce	O
+expression	O
+of	O
+VEGF	O
+in	O
+other	O
+cells	O
+[	O
+57	O
+]	O
+,	O
+this	O
+ATP	O
+release	O
+may	O
+contribute	O
+to	O
+growth	O
+factor	O
+signaling	O
+by	O
+the	O
+diseased	O
+RPE	O
+.	O
+
+Fig	O
+.	O
+2Chemical	O
+ischemia	O
+triggers	O
+ATP	O
+release	O
+from	O
+ARPE	O
+-	O
+19	O
+cells	O
+.	O
+
+ATP	O
+release	O
+was	O
+measured	O
+in	O
+the	O
+bath	O
+directly	O
+from	O
+cells	O
+plated	O
+in	O
+96	O
+-	O
+well	O
+plates	O
+to	O
+which	O
+the	O
+luciferin	O
+-	O
+luciferase	O
+reaction	O
+mixture	O
+was	O
+added	O
+[	O
+51	O
+]	O
+.	O
+
+Left	O
+Levels	O
+of	O
+ATP	O
+in	O
+the	O
+bath	O
+after	O
+addition	O
+of	O
+5	O
+mM	O
+NaCN	O
+to	O
+the	O
+cells	O
+.	O
+
+Measurement	O
+began	O
+1	O
+min	O
+after	O
+addition	O
+of	O
+NaCN	O
+or	O
+control	O
+solution	O
+to	O
+wells	O
+.	O
+
+Right	O
+Levels	O
+of	O
+ATP	O
+measured	O
+at	O
+the	O
+peak	O
+,	O
+3	O
+min	O
+after	O
+addition	O
+of	O
+NaCN	O
+(	O
+n	O
+=	O
+12	O
+)	O
+.	O
+
+Levels	O
+were	O
+normalized	O
+to	O
+concurrent	O
+levels	O
+in	O
+control	O
+(	O
+n	O
+=	O
+14	O
+)	O
+.	O
+
+Symbols	O
+and	O
+bars	O
+represent	O
+mean	O
++	O
+/	O
+-	O
+SE	O
+,	O
+*	O
+p	O
+<	O
+0	O
+.	O
+001	O
+
+The	O
+particular	O
+conduit	O
+for	O
+ATP	O
+release	O
+varies	O
+with	O
+the	O
+stimuli	O
+.	O
+
+The	O
+release	O
+in	O
+response	O
+to	O
+hypotonic	O
+challenge	O
+is	O
+largely	O
+dependent	O
+upon	O
+CFTR	O
+,	O
+as	O
+it	O
+was	O
+prevented	O
+by	O
+the	O
+specific	O
+CFTR	O
+inhibitor	O
+CFTR172	O
+in	O
+addition	O
+to	O
+the	O
+more	O
+general	O
+blocker	O
+glybenclamide	O
+[	O
+50	O
+]	O
+.	O
+
+While	O
+the	O
+precise	O
+mechanisms	O
+by	O
+which	O
+CFTR	O
+contributes	O
+to	O
+this	O
+release	O
+are	O
+not	O
+yet	O
+known	O
+,	O
+a	O
+role	O
+for	O
+CFTR	O
+in	O
+ATP	O
+release	O
+into	O
+subretinal	O
+space	O
+is	O
+consistent	O
+with	O
+the	O
+reduction	O
+of	O
+certain	O
+ERG	O
+components	O
+in	O
+cftr	O
+-	O
+/	O
+-	O
+mice	B
+[	O
+58	O
+]	O
+and	O
+with	O
+the	O
+ability	O
+of	O
+apical	O
+ATP	O
+to	O
+activate	O
+conductances	O
+associated	O
+with	O
+these	O
+ERG	O
+components	O
+[	O
+43	O
+]	O
+.	O
+
+The	O
+release	O
+of	O
+ATP	O
+is	O
+also	O
+largely	O
+blocked	O
+by	O
+the	O
+vesicular	O
+transport	O
+inhibitor	O
+brefeldin	O
+A	O
+,	O
+suggesting	O
+the	O
+two	O
+processes	O
+occurred	O
+in	O
+series	O
+whereby	O
+ATP	O
+efflux	O
+follows	O
+the	O
+insertion	O
+of	O
+vesicles	O
+containing	O
+CFTR	O
+into	O
+the	O
+plasma	O
+membrane	O
+.	O
+
+Although	O
+the	O
+Ca2	O
++	O
+chelator	O
+BAPTA	O
+blocks	O
+this	O
+ATP	O
+release	O
+[	O
+50	O
+]	O
+,	O
+raising	O
+Ca2	O
++	O
+alone	O
+with	O
+ionophore	O
+ionomycin	O
+does	O
+not	O
+itself	O
+initiate	O
+release	O
+[	O
+48	O
+]	O
+.	O
+
+This	O
+necessary	O
+but	O
+not	O
+sufficient	O
+contribution	O
+of	O
+Ca2	O
++	O
+also	O
+supports	O
+a	O
+role	O
+for	O
+vesicular	O
+insertion	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+release	O
+following	O
+hypotonic	O
+challenge	O
+,	O
+the	O
+ATP	O
+release	O
+in	O
+response	O
+to	O
+NMDA	O
+does	O
+not	O
+involve	O
+CFTR	O
+[	O
+51	O
+]	O
+.	O
+
+Release	O
+is	O
+blocked	O
+by	O
+NPPB	O
+,	O
+however	O
+,	O
+suggesting	O
+another	O
+type	O
+of	O
+anion	O
+channel	O
+could	O
+serve	O
+as	O
+a	O
+conduit	O
+for	O
+ATP	O
+release	O
+.	O
+
+The	O
+presence	O
+of	O
+parallel	O
+mechanisms	O
+coexisting	O
+on	O
+the	O
+same	O
+cell	O
+for	O
+ATP	O
+release	O
+triggered	O
+by	O
+either	O
+agonists	O
+or	O
+by	O
+cell	O
+swelling	O
+has	O
+also	O
+been	O
+reported	O
+in	O
+astrocytes	O
+[	O
+59	O
+]	O
+and	O
+may	O
+reflect	O
+the	O
+multiple	O
+roles	O
+of	O
+purinergic	O
+signaling	O
+within	O
+a	O
+given	O
+tissue	O
+.	O
+
+As	O
+both	O
+stimuli	O
+lead	O
+to	O
+release	O
+across	O
+the	O
+apical	O
+membrane	O
+into	O
+subretinal	O
+space	O
+,	O
+both	O
+are	O
+expected	O
+to	O
+influence	O
+signaling	O
+in	O
+the	O
+microenvironment	O
+.	O
+
+Interconversion	O
+of	O
+purines	O
+in	O
+subretinal	O
+space	O
+
+The	O
+interconversion	O
+of	O
+nucleotides	O
+and	O
+nucleosides	O
+each	O
+capable	O
+of	O
+stimulating	O
+distinct	O
+receptors	O
+makes	O
+the	O
+purinergic	O
+signaling	O
+system	O
+of	O
+particular	O
+interest	O
+in	O
+a	O
+confined	O
+region	O
+such	O
+as	O
+the	O
+subretinal	O
+space	O
+.	O
+
+The	O
+main	O
+enzymes	O
+responsible	O
+for	O
+dephosphorylating	O
+extracellular	O
+ATP	O
+on	O
+the	O
+RPE	O
+cells	O
+have	O
+been	O
+analyzed	O
+and	O
+a	O
+basic	O
+understanding	O
+of	O
+their	O
+regulation	O
+has	O
+begun	O
+.	O
+
+This	O
+section	O
+first	O
+describes	O
+the	O
+enzymes	O
+that	O
+act	O
+on	O
+ATP	O
+and	O
+ADP	O
+,	O
+followed	O
+by	O
+enzymes	O
+which	O
+convert	O
+AMP	O
+into	O
+adenosine	O
+.	O
+
+The	O
+dephosphorylation	O
+of	O
+extracellular	O
+ATP	O
+by	O
+RPE	O
+cells	O
+involves	O
+enzymes	O
+from	O
+multiple	O
+families	O
+[	O
+40	O
+]	O
+,	O
+as	O
+found	O
+in	O
+airway	O
+epithelial	O
+cells	O
+[	O
+60	O
+]	O
+.	O
+
+Degradation	O
+of	O
+ATP	O
+by	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+fresh	O
+bovine	B
+eyecup	O
+and	O
+by	O
+ARPE	O
+-	O
+19	O
+cells	O
+is	O
+inhibited	O
+by	O
+ARL67156	O
+or	O
+beta	O
+gamma	O
+mATP	O
+.	O
+
+Message	O
+for	O
+eNPP1	O
+,	O
+eNPP2	O
+,	O
+and	O
+eNPP3	O
+is	O
+present	O
+in	O
+ARPE	O
+-	O
+19	O
+cells	O
+,	O
+consistent	O
+with	O
+the	O
+preference	O
+of	O
+beta	O
+gamma	O
+mATP	O
+for	O
+members	O
+of	O
+the	O
+eNPP	O
+family	O
+[	O
+61	O
+]	O
+.	O
+
+The	O
+cells	O
+also	O
+express	O
+NTPDase2	O
+,	O
+and	O
+NTPDase3	O
+,	O
+although	O
+the	O
+intermittent	O
+presence	O
+of	O
+NTPDase1	O
+likely	O
+reflects	O
+a	O
+regulated	O
+process	O
+[	O
+40	O
+]	O
+.	O
+
+Ecto	O
+-	O
+alkaline	O
+phosphatase	O
+has	O
+no	O
+effect	O
+on	O
+ATP	O
+degradation	O
+in	O
+RPE	O
+cells	O
+,	O
+in	O
+contrast	O
+to	O
+its	O
+considerable	O
+contribution	O
+in	O
+airway	O
+epithelium	O
+[	O
+62	O
+]	O
+.	O
+
+The	O
+putative	O
+contribution	O
+from	O
+diphosphokinases	O
+to	O
+interconversion	O
+of	O
+subretinal	O
+purines	O
+is	O
+presently	O
+unknown	O
+.	O
+
+Extracellular	O
+AMP	O
+is	O
+rapidly	O
+dephosphorylated	O
+into	O
+adenosine	O
+in	O
+subretinal	O
+space	O
+.	O
+
+The	O
+production	O
+of	O
+adenosine	O
+from	O
+ATP	O
+at	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+bovine	B
+RPE	O
+eyecup	O
+is	O
+inhibited	O
+by	O
+the	O
+ecto	O
+-	O
+5	O
+'	O
+-	O
+nucleotidase	O
+inhibitor	O
+alpha	O
+beta	O
+mADP	O
+,	O
+confirming	O
+a	O
+role	O
+for	O
+this	O
+enzyme	O
+[	O
+63	O
+]	O
+.	O
+
+The	O
+enzyme	O
+is	O
+localized	O
+to	O
+rat	B
+RPE	O
+and	O
+ARPE	O
+-	O
+19	O
+cells	O
+immunohistochemicall	O
+.	O
+
+Degradation	O
+of	O
+5	O
+'	O
+AMP	O
+is	O
+highest	O
+near	O
+the	O
+subretinal	O
+space	O
+of	O
+rat	B
+retina	O
+[	O
+63	O
+]	O
+,	O
+although	O
+localization	O
+in	O
+mouse	B
+indicated	O
+larger	O
+amounts	O
+of	O
+ecto	O
+-	O
+5	O
+'	O
+-	O
+nucleotidase	O
+at	O
+the	O
+tips	O
+of	O
+adjacent	O
+M	O
+u	O
+ller	O
+cells	O
+[	O
+64	O
+]	O
+.	O
+
+Levamisole	O
+does	O
+not	O
+inhibit	O
+the	O
+dephosphorylation	O
+of	O
+5	O
+'	O
+AMP	O
+by	O
+the	O
+RPE	O
+,	O
+consistent	O
+with	O
+the	O
+absence	O
+of	O
+substantial	O
+ecto	O
+-	O
+alkaline	O
+phosphatase	O
+in	O
+subretinal	O
+space	O
+.	O
+
+The	O
+presence	O
+of	O
+light	O
+may	O
+alter	O
+the	O
+levels	O
+of	O
+adenosine	O
+in	O
+subretinal	O
+space	O
+.	O
+
+Epinephrine	O
+is	O
+released	O
+at	O
+the	O
+onset	O
+of	O
+light	O
+[	O
+65	O
+]	O
+and	O
+stimulation	O
+of	O
+the	O
+RPE	O
+with	O
+epinephrine	O
+can	O
+decrease	O
+activity	O
+of	O
+ecto	O
+-	O
+5	O
+'	O
+-	O
+nucleotidase	O
+[	O
+63	O
+]	O
+.	O
+
+While	O
+norepinephrine	O
+and	O
+phenylephrine	O
+lead	O
+to	O
+similar	O
+decreases	O
+in	O
+enzyme	O
+activity	O
+,	O
+prazosin	O
+and	O
+corynanthine	O
+block	O
+the	O
+effects	O
+of	O
+norepinephrine	O
+,	O
+implicating	O
+the	O
+alpha	O
+1	O
+epinephrine	O
+receptor	O
+in	O
+the	O
+inhibition	O
+of	O
+ecto	O
+-	O
+5	O
+'	O
+-	O
+nucleotidase	O
+[	O
+63	O
+]	O
+.	O
+
+The	O
+kinetics	O
+of	O
+inhibition	O
+are	O
+consistent	O
+with	O
+cleavage	O
+of	O
+the	O
+nucleotidase	O
+from	O
+its	O
+GPI	O
+anchor	O
+.	O
+
+The	O
+phagocytosis	O
+of	O
+rod	O
+outer	O
+segments	O
+is	O
+maximal	O
+shortly	O
+after	O
+light	O
+onset	O
+[	O
+16	O
+]	O
+,	O
+and	O
+this	O
+phagocytosis	O
+is	O
+inhibited	O
+by	O
+adenosine	O
+[	O
+29	O
+]	O
+.	O
+
+The	O
+ability	O
+of	O
+epinephrine	O
+released	O
+by	O
+the	O
+illuminated	O
+retina	O
+to	O
+reduce	O
+ecto	O
+-	O
+5	O
+'	O
+-	O
+nucleotidase	O
+activity	O
+and	O
+consequently	O
+adenosine	O
+levels	O
+may	O
+relieve	O
+this	O
+inhibition	O
+and	O
+enhance	O
+the	O
+rate	O
+of	O
+phagocytosis	O
+at	O
+light	O
+onset	O
+.	O
+
+Physiologic	O
+effects	O
+of	O
+subretinal	O
+purines	O
+on	O
+the	O
+RPE	O
+and	O
+photoreceptors	O
+
+The	O
+number	O
+of	O
+purinergic	O
+receptors	O
+on	O
+both	O
+photoreceptor	O
+and	O
+RPE	O
+membranes	O
+suggests	O
+purines	O
+make	O
+multiple	O
+contributions	O
+to	O
+the	O
+physiology	O
+of	O
+the	O
+outer	O
+retina	O
+.	O
+
+Our	O
+increased	O
+understanding	O
+of	O
+how	O
+agonist	O
+levels	O
+in	O
+subretinal	O
+space	O
+are	O
+controlled	O
+has	O
+begun	O
+to	O
+indicate	O
+how	O
+and	O
+when	O
+this	O
+contribution	O
+may	O
+occur	O
+.	O
+
+Future	O
+research	O
+will	O
+involve	O
+applying	O
+these	O
+findings	O
+from	O
+isolated	O
+systems	O
+to	O
+intact	O
+RPE	O
+-	O
+photoreceptor	O
+models	O
+,	O
+and	O
+pursuing	O
+the	O
+role	O
+of	O
+defective	O
+purinergic	O
+regulation	O
+in	O
+ocular	O
+disease	O
+.	O
+
+While	O
+it	O
+is	O
+unlikely	O
+that	O
+ATP	O
+released	O
+across	O
+the	O
+apical	O
+membrane	O
+of	O
+the	O
+RPE	O
+can	O
+diffuse	O
+to	O
+these	O
+P2	O
+receptors	O
+in	O
+the	O
+outer	O
+plexiform	O
+layer	O
+given	O
+the	O
+ecto	O
+-	O
+ATPase	O
+activity	O
+in	O
+the	O
+synaptic	O
+clef	O
+[	O
+25	O
+]	O
+,	O
+stimulation	O
+of	O
+receptors	O
+elsewhere	O
+on	O
+the	O
+photoreceptor	O
+membrane	O
+is	O
+possible	O
+.	O
+
+It	O
+would	O
+be	O
+interesting	O
+to	O
+determine	O
+whether	O
+ATP	O
+released	O
+from	O
+the	O
+RPE	O
+and	O
+converted	O
+to	O
+adenosine	O
+by	O
+ecto	O
+-	O
+nucleotidases	O
+can	O
+actually	O
+modulate	O
+the	O
+response	O
+to	O
+light	O
+by	O
+stimulating	O
+the	O
+A2A	O
+receptors	O
+on	O
+photoreceptor	O
+outer	O
+segments	O
+.	O
+
+The	O
+impact	O
+of	O
+purinergic	O
+signaling	O
+on	O
+chronic	O
+ocular	O
+diseases	O
+is	O
+also	O
+of	O
+interest	O
+,	O
+such	O
+as	O
+the	O
+role	O
+of	O
+ischemia	O
+-	O
+driven	O
+ATP	O
+release	O
+in	O
+VEGF	O
+production	O
+.	O
+
+While	O
+the	O
+small	O
+size	O
+of	O
+subretinal	O
+space	O
+can	O
+complicate	O
+pharmacologic	O
+manipulation	O
+within	O
+the	O
+intact	O
+RPE	O
+-	O
+photoreceptor	O
+complex	O
+,	O
+molecular	O
+approaches	O
+may	O
+provide	O
+new	O
+insight	O
+into	O
+how	O
+endogenous	O
+purines	O
+in	O
+subretinal	O
+space	O
+affect	O
+the	O
+physiology	O
+,	O
+and	O
+pathophysiology	O
+,	O
+of	O
+both	O
+RPE	O
+and	O
+photoreceptors	O
+.	O
+
+Comparative	O
+Genome	O
+Analysis	O
+of	O
+Filamentous	O
+Fungi	O
+Reveals	O
+Gene	O
+Family	O
+Expansions	O
+Associated	O
+with	O
+Fungal	O
+Pathogenesis	O
+
+Abstract	O
+
+Fungi	O
+and	O
+oomycetes	O
+are	O
+the	O
+causal	O
+agents	O
+of	O
+many	O
+of	O
+the	O
+most	O
+serious	O
+diseases	O
+of	O
+plants	O
+.	O
+
+Here	O
+we	O
+report	O
+a	O
+detailed	O
+comparative	O
+analysis	O
+of	O
+the	O
+genome	O
+sequences	O
+of	O
+thirty	O
+-	O
+six	O
+species	O
+of	O
+fungi	O
+and	O
+oomycetes	O
+,	O
+including	O
+seven	O
+plant	O
+pathogenic	O
+species	O
+,	O
+that	O
+aims	O
+to	O
+explore	O
+the	O
+common	O
+genetic	O
+features	O
+associated	O
+with	O
+plant	O
+disease	O
+-	O
+causing	O
+species	O
+.	O
+
+The	O
+predicted	O
+translational	O
+products	O
+of	O
+each	O
+genome	O
+have	O
+been	O
+clustered	O
+into	O
+groups	O
+of	O
+potential	O
+orthologues	O
+using	O
+Markov	O
+Chain	O
+Clustering	O
+and	O
+the	O
+data	O
+integrated	O
+into	O
+the	O
+e	O
+-	O
+Fungi	O
+object	O
+-	O
+oriented	O
+data	O
+warehouse	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+e	O
+-	O
+fungi	O
+.	O
+org	O
+.	O
+uk	O
+/	O
+)	O
+.	O
+
+Analysis	O
+of	O
+the	O
+species	O
+distribution	O
+of	O
+members	O
+of	O
+these	O
+clusters	O
+has	O
+identified	O
+proteins	O
+that	O
+are	O
+specific	O
+to	O
+filamentous	O
+fungal	O
+species	O
+and	O
+a	O
+group	O
+of	O
+proteins	O
+found	O
+only	O
+in	O
+plant	O
+pathogens	O
+.	O
+
+By	O
+comparing	O
+the	O
+gene	O
+inventories	O
+of	O
+filamentous	O
+,	O
+ascomycetous	O
+phytopathogenic	O
+and	O
+free	O
+-	O
+living	O
+species	O
+of	O
+fungi	O
+,	O
+we	O
+have	O
+identified	O
+a	O
+set	O
+of	O
+gene	O
+families	O
+that	O
+appear	O
+to	O
+have	O
+expanded	O
+during	O
+the	O
+evolution	O
+of	O
+phytopathogens	O
+and	O
+may	O
+therefore	O
+serve	O
+important	O
+roles	O
+in	O
+plant	O
+disease	O
+.	O
+
+We	O
+have	O
+also	O
+characterised	O
+the	O
+predicted	O
+set	O
+of	O
+secreted	O
+proteins	O
+encoded	O
+by	O
+each	O
+genome	O
+and	O
+identified	O
+a	O
+set	O
+of	O
+protein	O
+families	O
+which	O
+are	O
+significantly	O
+over	O
+-	O
+represented	O
+in	O
+the	O
+secretomes	O
+of	O
+plant	O
+pathogenic	O
+fungi	O
+,	O
+including	O
+putative	O
+effector	O
+proteins	O
+that	O
+might	O
+perturb	O
+host	O
+cell	O
+biology	O
+during	O
+plant	O
+infection	O
+.	O
+
+The	O
+results	O
+demonstrate	O
+the	O
+potential	O
+of	O
+comparative	O
+genome	O
+analysis	O
+for	O
+exploring	O
+the	O
+evolution	O
+of	O
+eukaryotic	O
+microbial	O
+pathogenesis	O
+.	O
+
+Introduction	O
+
+Fungi	O
+and	O
+oomycetes	O
+are	O
+responsible	O
+for	O
+many	O
+of	O
+the	O
+world	O
+'	O
+s	O
+most	O
+devastating	O
+plant	O
+diseases	O
+including	O
+late	O
+blight	O
+disease	O
+of	O
+potato	B
+,	O
+caused	O
+by	O
+the	O
+oomycete	O
+pathogen	O
+Phytophthora	B
+infestans	I
+and	O
+rice	B
+blast	O
+disease	O
+caused	O
+by	O
+the	O
+ascomycete	O
+fungus	O
+Magnaporthe	B
+grisea	I
+,	O
+both	O
+of	O
+which	O
+are	O
+responsible	O
+for	O
+very	O
+significant	O
+harvest	O
+losses	O
+each	O
+year	O
+.	O
+
+The	O
+enormous	O
+diversity	O
+of	O
+crop	O
+diseases	O
+caused	O
+by	O
+these	O
+eukaryotic	O
+micro	O
+-	O
+organisms	O
+poses	O
+a	O
+difficult	O
+challenge	O
+to	O
+the	O
+development	O
+of	O
+durable	O
+disease	O
+control	O
+strategies	O
+.	O
+
+Identifying	O
+common	O
+underlying	O
+molecular	O
+mechanisms	O
+necessary	O
+for	O
+pathogenesis	O
+in	O
+a	O
+wide	O
+range	O
+of	O
+pathogenic	O
+species	O
+is	O
+therefore	O
+a	O
+major	O
+goal	O
+of	O
+current	O
+research	O
+.	O
+
+Approximately	O
+100	O
+,	O
+000	O
+species	O
+of	O
+fungi	O
+have	O
+so	O
+far	O
+been	O
+described	O
+,	O
+but	O
+only	O
+a	O
+very	O
+small	O
+proportion	O
+of	O
+these	O
+are	O
+pathogenic	O
+[	O
+1	O
+]	O
+.	O
+
+Phylogenetic	O
+studies	O
+have	O
+,	O
+meanwhile	O
+,	O
+shown	O
+that	O
+disease	O
+-	O
+causing	O
+pathogens	O
+are	O
+not	O
+necessarily	O
+closely	O
+-	O
+related	O
+to	O
+each	O
+other	O
+,	O
+and	O
+in	O
+fact	O
+are	O
+spread	O
+throughout	O
+all	O
+taxonomic	O
+groups	O
+of	O
+fungi	O
+,	O
+often	O
+showing	O
+a	O
+close	O
+evolutionary	O
+relationship	O
+to	O
+non	O
+-	O
+pathogenic	O
+species	O
+[	O
+2	O
+]	O
+,	O
+[	O
+3	O
+]	O
+.	O
+
+It	O
+therefore	O
+seems	O
+likely	O
+that	O
+phytopathogenicity	O
+has	O
+evolved	O
+as	O
+a	O
+trait	O
+many	O
+times	O
+during	O
+fungal	O
+and	O
+oomycete	O
+evolution	O
+[	O
+1	O
+]	O
+and	O
+in	O
+some	O
+groups	O
+may	O
+be	O
+ancestral	O
+to	O
+the	O
+more	O
+recent	O
+emergence	O
+of	O
+saprotrophic	O
+species	O
+.	O
+
+A	O
+significant	O
+effort	O
+has	O
+gone	O
+into	O
+the	O
+identification	O
+of	O
+pathogenicity	O
+determinants	O
+-	O
+individual	O
+genes	O
+that	O
+are	O
+essential	O
+for	O
+a	O
+pathogen	O
+to	O
+invade	O
+a	O
+host	O
+plant	O
+successfully	O
+,	O
+but	O
+which	O
+are	O
+dispensable	O
+for	O
+saprophytic	O
+growth	O
+[	O
+4	O
+]	O
+,	O
+[	O
+5	O
+]	O
+.	O
+
+However	O
+,	O
+far	O
+from	O
+being	O
+novel	O
+proteins	O
+encoded	O
+only	O
+by	O
+the	O
+genomes	O
+of	O
+pathogenic	O
+fungi	O
+,	O
+many	O
+of	O
+the	O
+genes	O
+identified	O
+so	O
+far	O
+encode	O
+components	O
+of	O
+conserved	O
+signalling	O
+pathways	O
+that	O
+are	O
+found	O
+in	O
+all	O
+species	O
+of	O
+fungi	O
+,	O
+such	O
+as	O
+the	O
+mitogen	O
+activated	O
+protein	O
+(	O
+MAP	O
+)	O
+kinases	O
+[	O
+6	O
+]	O
+,	O
+adenylate	O
+cyclase	O
+[	O
+7	O
+]	O
+and	O
+G	O
+-	O
+protein	O
+subunits	O
+[	O
+8	O
+]	O
+.	O
+
+The	O
+MAP	O
+kinase	O
+pathways	O
+,	O
+for	O
+example	O
+,	O
+have	O
+been	O
+studied	O
+extensively	O
+in	O
+the	O
+budding	O
+yeast	B
+Saccharomyces	B
+cerevisiae	I
+and	O
+trigger	O
+morphological	O
+and	O
+biochemical	O
+changes	O
+in	O
+response	O
+to	O
+external	O
+stimuli	O
+such	O
+as	O
+starvation	O
+stress	O
+or	O
+hyperosmotic	O
+conditions	O
+[	O
+9	O
+]	O
+.	O
+
+In	O
+pathogenic	O
+fungi	O
+,	O
+components	O
+of	O
+these	O
+pathways	O
+have	O
+evolved	O
+instead	O
+to	O
+regulate	O
+the	O
+morphological	O
+changes	O
+associated	O
+with	O
+plant	O
+infection	O
+.	O
+
+For	O
+example	O
+,	O
+appressorium	O
+formation	O
+in	O
+the	O
+rice	B
+blast	I
+fungus	I
+Magnaporthe	B
+grisea	I
+,	O
+stimulated	O
+by	O
+hard	O
+,	O
+hydrophobic	O
+surfaces	O
+is	O
+regulated	O
+by	O
+a	O
+MAP	O
+kinase	O
+cascade	O
+[	O
+10	O
+]	O
+.	O
+
+This	O
+pathway	O
+deploys	O
+novel	O
+classes	O
+of	O
+G	O
+-	O
+protein	O
+coupled	O
+receptors	O
+not	O
+found	O
+in	O
+the	O
+genome	O
+of	O
+S	B
+.	I
+cerevisiae	I
+[	O
+11	O
+]	O
+,	O
+but	O
+the	O
+inductive	O
+signal	O
+is	O
+transmitted	O
+via	O
+a	O
+MAP	O
+kinase	O
+,	O
+Pmk1	O
+,	O
+that	O
+is	O
+a	O
+functional	O
+homologue	O
+of	O
+the	O
+yeast	B
+Fus3	O
+MAP	O
+kinase	O
+where	O
+it	O
+serves	O
+a	O
+role	O
+in	O
+pheromone	O
+signalling	O
+[	O
+10	O
+]	O
+.	O
+
+Similarly	O
+,	O
+conserved	O
+metabolic	O
+pathways	O
+such	O
+as	O
+the	O
+glyoxylate	O
+cycle	O
+and	O
+amino	O
+acid	O
+biosynthesis	O
+are	O
+also	O
+important	O
+for	O
+pathogenesis	O
+[	O
+12	O
+]	O
+-	O
+[	O
+14	O
+]	O
+.	O
+
+This	O
+may	O
+in	O
+some	O
+cases	O
+reflect	O
+the	O
+nutritional	O
+environment	O
+the	O
+pathogen	O
+encounters	O
+when	O
+growing	O
+in	O
+the	O
+host	O
+plant	O
+tissue	O
+,	O
+and	O
+in	O
+others	O
+shows	O
+the	O
+importance	O
+of	O
+simple	O
+metabolites	O
+for	O
+pathogenic	O
+processes	O
+,	O
+such	O
+as	O
+the	O
+role	O
+of	O
+glycerol	O
+as	O
+a	O
+compatible	O
+solute	O
+for	O
+generating	O
+turgor	O
+pressure	O
+in	O
+the	O
+appressorium	O
+of	O
+M	B
+.	I
+grisea	I
+[	O
+15	O
+]	O
+.	O
+
+It	O
+is	O
+undoubtedly	O
+the	O
+case	O
+,	O
+however	O
+,	O
+that	O
+identification	O
+of	O
+such	O
+genes	O
+has	O
+also	O
+been	O
+a	O
+consequence	O
+of	O
+the	O
+manner	O
+in	O
+which	O
+these	O
+studies	O
+have	O
+been	O
+carried	O
+out	O
+,	O
+often	O
+using	O
+yeast	B
+as	O
+a	O
+model	O
+organism	O
+to	O
+test	O
+hypotheses	O
+concerning	O
+the	O
+developmental	O
+biology	O
+and	O
+biochemistry	O
+of	O
+plant	O
+pathogenic	O
+species	O
+.	O
+
+Other	O
+pathogenicity	O
+factors	O
+identified	O
+to	O
+date	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+involved	O
+in	O
+functions	O
+associated	O
+with	O
+host	O
+infection	O
+,	O
+such	O
+as	O
+plant	O
+cell	O
+wall	O
+degradation	O
+,	O
+toxin	O
+biosynthesis	O
+and	O
+protection	O
+against	O
+plant	O
+defences	O
+[	O
+reviewed	O
+in	O
+5	O
+]	O
+.	O
+
+Identification	O
+of	O
+a	O
+pathogenicity	O
+factor	O
+generally	O
+involves	O
+making	O
+a	O
+mutant	O
+fungal	O
+strain	O
+with	O
+a	O
+non	O
+-	O
+functioning	O
+version	O
+of	O
+the	O
+gene	O
+by	O
+targeted	O
+gene	O
+deletion	O
+and	O
+assaying	O
+the	O
+ability	O
+of	O
+the	O
+mutant	O
+to	O
+cause	O
+disease	O
+.	O
+
+Therefore	O
+,	O
+most	O
+pathogenicity	O
+factors	O
+identified	O
+so	O
+far	O
+,	O
+have	O
+been	O
+validated	O
+in	O
+only	O
+a	O
+small	O
+number	O
+of	O
+genetically	O
+tractable	O
+pathogenic	O
+fungi	O
+,	O
+such	O
+as	O
+M	B
+.	I
+grisea	I
+and	O
+the	O
+corn	B
+smut	O
+Ustilago	B
+maydis	I
+and	O
+many	O
+of	O
+the	O
+advances	O
+in	O
+understanding	O
+the	O
+developmental	O
+biology	O
+of	O
+plant	O
+infection	O
+have	O
+occurred	O
+in	O
+these	O
+model	O
+pathogens	O
+[	O
+16	O
+]	O
+,	O
+[	O
+17	O
+]	O
+.	O
+
+However	O
+,	O
+there	O
+are	O
+severe	O
+limitations	O
+to	O
+studying	O
+pathogenicity	O
+by	O
+mutating	O
+one	O
+gene	O
+at	O
+a	O
+time	O
+and	O
+working	O
+predominantly	O
+with	O
+a	O
+hypothesis	O
+-	O
+driven	O
+,	O
+reverse	O
+genetics	O
+approach	O
+.	O
+
+Many	O
+virulence	O
+-	O
+associated	O
+processes	O
+,	O
+for	O
+instance	O
+,	O
+such	O
+as	O
+the	O
+development	O
+of	O
+infection	O
+structures	O
+and	O
+haustoria	O
+,	O
+are	O
+likely	O
+to	O
+involve	O
+a	O
+large	O
+number	O
+of	O
+gene	O
+products	O
+and	O
+so	O
+there	O
+is	O
+likely	O
+to	O
+be	O
+redundancy	O
+in	O
+gene	O
+function	O
+.	O
+
+One	O
+example	O
+of	O
+this	O
+is	O
+cutinase	O
+,	O
+a	O
+type	O
+of	O
+methyl	O
+esterase	O
+that	O
+hydrolyses	O
+the	O
+protective	O
+cutin	O
+layer	O
+present	O
+on	O
+the	O
+outside	O
+of	O
+the	O
+plant	O
+epidermis	O
+.	O
+
+Cutinase	O
+was	O
+excluded	O
+as	O
+a	O
+pathogencity	O
+factor	O
+for	O
+M	B
+.	I
+grisea	I
+on	O
+the	O
+basis	O
+that	O
+a	O
+mutant	O
+strain	O
+containing	O
+a	O
+non	O
+-	O
+functional	O
+cutinase	O
+-	O
+encoding	O
+gene	O
+was	O
+still	O
+able	O
+to	O
+cause	O
+rice	B
+blast	O
+disease	O
+[	O
+18	O
+]	O
+.	O
+
+However	O
+,	O
+sequencing	O
+of	O
+the	O
+M	B
+.	I
+grisea	I
+genome	O
+has	O
+shown	O
+the	O
+presence	O
+of	O
+eight	O
+potential	O
+cutinase	O
+-	O
+encoding	O
+genes	O
+implicated	O
+in	O
+virulence	O
+[	O
+19	O
+]	O
+.	O
+
+Additionally	O
+,	O
+targeted	O
+gene	O
+deletion	O
+is	O
+not	O
+feasible	O
+in	O
+many	O
+important	O
+pathogens	O
+and	O
+the	O
+normal	O
+definition	O
+of	O
+fungal	O
+pathogenicity	O
+cannot	O
+be	O
+applied	O
+in	O
+the	O
+case	O
+of	O
+obligate	O
+biotrophs	O
+,	O
+such	O
+as	O
+the	O
+powdery	O
+mildew	O
+fungus	O
+Blumeria	B
+graminis	I
+,	O
+which	O
+cannot	O
+be	O
+cultured	O
+away	O
+from	O
+living	O
+host	O
+plants	O
+.	O
+
+Therefore	O
+,	O
+new	O
+approaches	O
+are	O
+needed	O
+to	O
+identify	O
+genes	O
+that	O
+are	O
+vital	O
+for	O
+the	O
+process	O
+of	O
+pathogenicity	O
+.	O
+
+These	O
+include	O
+high	O
+-	O
+throughput	O
+methods	O
+such	O
+as	O
+microarray	O
+analysis	O
+,	O
+serial	O
+analysis	O
+of	O
+gene	O
+expression	O
+(	O
+SAGE	O
+)	O
+,	O
+insertional	O
+mutagenesis	O
+,	O
+proteomics	O
+and	O
+metabolomics	O
+[	O
+19	O
+]	O
+,	O
+[	O
+20	O
+]	O
+and	O
+are	O
+dependent	O
+on	O
+the	O
+availability	O
+of	O
+genome	O
+sequence	O
+information	O
+.	O
+
+After	O
+the	O
+initial	O
+release	O
+of	O
+the	O
+genome	O
+of	O
+the	O
+budding	O
+yeast	B
+S	B
+.	I
+cerevisiae	I
+in	O
+1996	O
+[	O
+21	O
+]	O
+,	O
+the	O
+number	O
+of	O
+publicly	O
+available	O
+sequenced	O
+fungal	O
+genomes	O
+has	O
+recently	O
+risen	O
+very	O
+quickly	O
+.	O
+
+A	O
+large	O
+number	O
+of	O
+fungal	O
+genome	O
+sequences	O
+are	O
+now	O
+publicly	O
+available	O
+,	O
+including	O
+those	O
+from	O
+several	O
+phytopathogenic	O
+fungi	O
+,	O
+including	O
+M	B
+.	I
+grisea	I
+[	O
+22	O
+]	O
+,	O
+Ustilago	B
+maydis	I
+[	O
+23	O
+]	O
+,	O
+Gibberella	B
+zeae	I
+[	O
+24	O
+]	O
+(	O
+the	O
+causal	O
+agent	O
+of	O
+head	O
+blight	O
+of	O
+wheat	B
+and	O
+barley	B
+)	O
+,	O
+Stagonospora	B
+nodorum	I
+[	O
+25	O
+]	O
+(	O
+the	O
+causal	O
+agent	O
+of	O
+glume	O
+blotch	O
+of	O
+wheat	B
+)	O
+,	O
+the	O
+grey	O
+mould	O
+fungus	O
+Botrytis	B
+cinerea	I
+and	O
+the	O
+white	O
+mould	O
+fungus	O
+Sclerotinia	B
+sclerotiorum	I
+[	O
+reviewed	O
+in	O
+19	O
+]	O
+.	O
+
+Comparison	O
+of	O
+gene	O
+inventories	O
+of	O
+pathogenic	O
+and	O
+non	O
+-	O
+pathogenic	O
+organisms	O
+offers	O
+the	O
+most	O
+direct	O
+means	O
+of	O
+providing	O
+new	O
+information	O
+concerning	O
+the	O
+mechanisms	O
+involved	O
+in	O
+fungal	O
+and	O
+oomycete	O
+pathogenicity	O
+.	O
+
+In	O
+this	O
+report	O
+,	O
+we	O
+have	O
+developed	O
+and	O
+utilized	O
+the	O
+e	O
+-	O
+Fungi	O
+object	O
+-	O
+oriented	O
+data	O
+warehouse	O
+[	O
+26	O
+]	O
+,	O
+which	O
+contains	O
+data	O
+from	O
+36	O
+species	O
+of	O
+fungi	O
+and	O
+oomycetes	O
+and	O
+deploys	O
+a	O
+range	O
+of	O
+querying	O
+tools	O
+to	O
+allow	O
+interrogation	O
+of	O
+a	O
+significant	O
+amount	O
+of	O
+genome	O
+data	O
+in	O
+unparalleled	O
+detail	O
+.	O
+
+We	O
+report	O
+the	O
+identification	O
+of	O
+new	O
+gene	O
+families	O
+that	O
+are	O
+over	O
+represented	O
+in	O
+the	O
+genomes	O
+of	O
+filamentous	O
+ascomycete	O
+phytopathogens	O
+and	O
+define	O
+gene	O
+sets	O
+that	O
+are	O
+specific	O
+to	O
+diverse	O
+fungal	O
+pathogen	O
+species	O
+.	O
+
+We	O
+also	O
+report	O
+the	O
+putatively	O
+secreted	O
+protein	O
+sets	O
+which	O
+are	O
+produced	O
+by	O
+plant	O
+pathogenic	O
+fungi	O
+and	O
+which	O
+may	O
+play	O
+significant	O
+roles	O
+in	O
+plant	O
+infection	O
+.	O
+
+Results	O
+
+Identification	O
+of	O
+orthologous	O
+gene	O
+sets	O
+from	O
+fungal	O
+and	O
+oomcyete	O
+genomes	O
+
+Genome	O
+sequences	O
+and	O
+sets	O
+of	O
+predicted	O
+proteins	O
+were	O
+analysed	O
+from	O
+34	O
+species	O
+of	O
+fungi	O
+and	O
+2	O
+species	O
+of	O
+oomycete	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+In	O
+order	O
+to	O
+compare	O
+such	O
+a	O
+large	O
+number	O
+of	O
+genomes	O
+,	O
+an	O
+object	O
+-	O
+oriented	O
+data	O
+warehouse	O
+has	O
+been	O
+constructed	O
+known	O
+as	O
+e	O
+-	O
+Fungi	O
+[	O
+26	O
+]	O
+which	O
+integrates	O
+genomic	O
+data	O
+with	O
+a	O
+variety	O
+of	O
+functional	O
+data	O
+and	O
+has	O
+a	O
+powerful	O
+set	O
+of	O
+queries	O
+that	O
+enables	O
+sophisticated	O
+,	O
+whole	O
+-	O
+genome	O
+comparisons	O
+to	O
+be	O
+performed	O
+.	O
+
+To	O
+compare	O
+genome	O
+inventories	O
+,	O
+the	O
+entire	O
+set	O
+of	O
+predicted	O
+proteins	O
+from	O
+the	O
+36	O
+species	O
+(	O
+348	O
+,	O
+787	O
+proteins	O
+)	O
+were	O
+clustered	O
+using	O
+Markov	O
+Chain	O
+Clustering	O
+[	O
+27	O
+]	O
+as	O
+described	O
+previously	O
+[	O
+28	O
+]	O
+,	O
+[	O
+29	O
+]	O
+.	O
+
+A	O
+total	O
+of	O
+282	O
+,	O
+061	O
+predicted	O
+proteins	O
+were	O
+grouped	O
+into	O
+23	O
+,	O
+724	O
+clusters	O
+,	O
+each	O
+cluster	O
+representing	O
+a	O
+group	O
+of	O
+putative	O
+orthologues	O
+.	O
+
+The	O
+remaining	O
+66	O
+,	O
+934	O
+sequences	O
+were	O
+singletons	O
+,	O
+the	O
+products	O
+of	O
+unique	O
+genes	O
+.	O
+
+A	O
+total	O
+of	O
+165	O
+clusters	O
+contained	O
+proteins	O
+from	O
+all	O
+36	O
+species	O
+used	O
+in	O
+this	O
+study	O
+(	O
+Table	O
+S1	O
+)	O
+.	O
+
+Not	O
+surprisingly	O
+,	O
+they	O
+included	O
+many	O
+proteins	O
+involved	O
+in	O
+basic	O
+cellular	O
+processes	O
+,	O
+such	O
+as	O
+ribosomal	O
+proteins	O
+,	O
+components	O
+of	O
+transcription	O
+,	O
+translation	O
+and	O
+DNA	O
+replication	O
+apparatus	O
+,	O
+cytoskeletal	O
+proteins	O
+,	O
+histones	O
+,	O
+proteins	O
+involved	O
+in	O
+the	O
+secretory	O
+pathway	O
+,	O
+protein	O
+folding	O
+,	O
+protein	O
+sorting	O
+and	O
+ubiquitin	O
+-	O
+mediated	O
+proteolysis	O
+and	O
+enzymes	O
+involved	O
+in	O
+primary	O
+metabolism	O
+.	O
+
+Only	O
+16	O
+clusters	O
+contained	O
+proteins	O
+that	O
+were	O
+found	O
+in	O
+all	O
+34	O
+species	O
+of	O
+fungi	O
+,	O
+but	O
+which	O
+were	O
+absent	O
+from	O
+the	O
+two	O
+species	O
+of	O
+oomycete	O
+(	O
+Table	O
+S2	O
+)	O
+.	O
+
+This	O
+number	O
+of	O
+fungal	O
+-	O
+specific	O
+clusters	O
+is	O
+surprisingly	O
+low	O
+considering	O
+the	O
+phylogenetic	O
+distance	O
+between	O
+the	O
+oomycetes	O
+and	O
+fungi	O
+[	O
+30	O
+]	O
+.	O
+
+The	O
+list	O
+however	O
+,	O
+is	O
+consistent	O
+with	O
+the	O
+fundamental	O
+differences	O
+in	O
+biology	O
+between	O
+fungi	O
+and	O
+oomycetes	O
+and	O
+included	O
+proteins	O
+involved	O
+in	O
+fungal	O
+septation	O
+,	O
+glycosylation	O
+,	O
+transcriptional	O
+regulation	O
+,	O
+cell	O
+signalling	O
+,	O
+as	O
+well	O
+as	O
+two	O
+amino	O
+-	O
+acyl	O
+tRNA	O
+synthetases	O
+.	O
+
+The	O
+obligate	O
+mammalian	O
+pathogen	O
+Encephalitozoon	B
+cuniculi	I
+,	O
+a	O
+microsporidian	O
+fungus	O
+,	O
+has	O
+a	O
+reduced	O
+genome	O
+that	O
+codes	O
+only	O
+for	O
+1	O
+,	O
+997	O
+proteins	O
+and	O
+lacks	O
+genes	O
+encoding	O
+enzymes	O
+of	O
+many	O
+primary	O
+metabolic	O
+pathways	O
+such	O
+as	O
+the	O
+tricarboxylic	O
+acid	O
+cycle	O
+,	O
+fatty	O
+acid	O
+beta	O
+-	O
+oxidation	O
+,	O
+biosynthetic	O
+enzymes	O
+of	O
+the	O
+vast	O
+majority	O
+of	O
+amino	O
+acids	O
+,	O
+fatty	O
+acids	O
+and	O
+nucleotides	O
+,	O
+as	O
+well	O
+as	O
+components	O
+of	O
+the	O
+respiratory	O
+electron	O
+transport	O
+chain	O
+and	O
+F1	O
+-	O
+F0	O
+ATP	O
+synthase	O
+.	O
+
+It	O
+also	O
+lacks	O
+mitochondria	O
+and	O
+peroxisomes	O
+[	O
+31	O
+]	O
+.	O
+
+Therefore	O
+,	O
+we	O
+reasoned	O
+that	O
+the	O
+inclusion	O
+of	O
+this	O
+species	O
+in	O
+the	O
+analysis	O
+of	O
+MCL	O
+clusters	O
+is	O
+likely	O
+to	O
+result	O
+in	O
+underestimation	O
+of	O
+the	O
+number	O
+of	O
+groups	O
+of	O
+conserved	O
+proteins	O
+.	O
+
+By	O
+discarding	O
+E	B
+.	I
+cuniculi	I
+,	O
+there	O
+are	O
+377	O
+clusters	O
+that	O
+contained	O
+proteins	O
+from	O
+35	O
+species	O
+of	O
+fungi	O
+and	O
+oomycetes	O
+(	O
+Table	O
+S3	O
+)	O
+.	O
+
+This	O
+relatively	O
+small	O
+number	O
+of	O
+fungal	O
+-	O
+conserved	O
+clusters	O
+reflects	O
+the	O
+large	O
+evolutionary	O
+distance	O
+between	O
+members	O
+of	O
+the	O
+fungal	O
+kingdom	O
+,	O
+as	O
+well	O
+as	O
+complex	O
+patterns	O
+of	O
+gene	O
+gains	O
+and	O
+losses	O
+during	O
+the	O
+evolution	O
+of	O
+fungi	O
+.	O
+
+Basidiomycetes	O
+and	O
+ascomycetes	O
+are	O
+thought	O
+to	O
+have	O
+diverged	O
+nearly	O
+1	O
+,	O
+000	O
+million	O
+years	O
+ago	O
+[	O
+32	O
+]	O
+and	O
+the	O
+Saccharomycotina	O
+alone	O
+are	O
+more	O
+evolutionarily	O
+diverged	O
+than	O
+the	O
+Chordate	O
+phylum	O
+of	O
+the	O
+animal	O
+kingdom	O
+[	O
+33	O
+]	O
+.	O
+
+Since	O
+the	O
+divergence	O
+of	O
+Saccharomycotina	O
+(	O
+hemiascomycetes	O
+)	O
+and	O
+Pezizomycotina	O
+(	O
+euascomycetes	O
+)	O
+,	O
+the	O
+genomes	O
+of	O
+the	O
+latter	O
+have	O
+greatly	O
+increased	O
+in	O
+size	O
+,	O
+partly	O
+due	O
+to	O
+the	O
+appearance	O
+of	O
+novel	O
+genes	O
+related	O
+to	O
+the	O
+filamentous	O
+lifestyle	O
+.	O
+
+Lineage	O
+-	O
+specific	O
+gene	O
+losses	O
+have	O
+also	O
+been	O
+shown	O
+in	O
+a	O
+number	O
+of	O
+hemiascomycete	O
+species	O
+[	O
+34	O
+]	O
+.	O
+
+As	O
+well	O
+as	O
+the	O
+groups	O
+of	O
+proteins	O
+mentioned	O
+above	O
+(	O
+Table	O
+S1	O
+)	O
+,	O
+the	O
+fungal	O
+-	O
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+clusters	O
+included	O
+those	O
+containing	O
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+from	O
+primary	O
+metabolic	O
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+not	O
+present	O
+in	O
+E	B
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+cuniculi	I
+,	O
+such	O
+as	O
+the	O
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+,	O
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+acid	O
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+,	O
+fatty	O
+acid	O
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+,	O
+cholesterol	O
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+and	O
+nucleotide	O
+metabolism	O
+,	O
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+the	O
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+electron	O
+transport	O
+chain	O
+and	O
+F1	O
+-	O
+F0	O
+ATP	O
+synthase	O
+.	O
+
+The	O
+conserved	O
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+clusters	O
+also	O
+include	O
+a	O
+number	O
+of	O
+transporters	O
+(	O
+including	O
+mitochondrial	O
+transporters	O
+)	O
+,	O
+enzymes	O
+involved	O
+in	O
+haem	O
+biosynthesis	O
+,	O
+autophagy	O
+-	O
+related	O
+proteins	O
+,	O
+those	O
+involved	O
+in	O
+protein	O
+targeting	O
+to	O
+the	O
+peroxisome	O
+and	O
+vacuole	O
+and	O
+additional	O
+groups	O
+of	O
+proteins	O
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+in	O
+signal	O
+transduction	O
+that	O
+are	O
+not	O
+present	O
+in	O
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+cuniculi	I
+(	O
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+those	O
+involved	O
+in	O
+inosine	O
+triphosphate	O
+and	O
+leukotriene	O
+metabolism	O
+)	O
+.	O
+
+The	O
+analysis	O
+also	O
+showed	O
+there	O
+were	O
+105	O
+clusters	O
+that	O
+contained	O
+proteins	O
+from	O
+33	O
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+fungi	O
+(	O
+excluding	O
+E	B
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+)	O
+,	O
+but	O
+not	O
+from	O
+the	O
+two	O
+species	O
+of	O
+oomycete	O
+(	O
+see	O
+Table	O
+S4	O
+)	O
+.	O
+
+As	O
+well	O
+as	O
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+mentioned	O
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+(	O
+Table	O
+S2	O
+)	O
+,	O
+the	O
+group	O
+includes	O
+a	O
+number	O
+of	O
+clusters	O
+of	O
+transporters	O
+that	O
+are	O
+conserved	O
+in	O
+fungi	O
+but	O
+not	O
+found	O
+in	O
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+,	O
+as	O
+well	O
+as	O
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+in	O
+fungal	O
+cell	O
+wall	O
+synthesis	O
+,	O
+and	O
+lipid	O
+metabolism	O
+.	O
+
+It	O
+may	O
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+the	O
+case	O
+that	O
+the	O
+genomes	O
+of	O
+oomycete	O
+species	O
+do	O
+not	O
+possess	O
+orthologues	O
+of	O
+the	O
+fungal	O
+genes	O
+in	O
+these	O
+clusters	O
+,	O
+or	O
+alternatively	O
+,	O
+the	O
+large	O
+evolutionary	O
+distance	O
+between	O
+the	O
+oomycetes	O
+and	O
+fungi	O
+mean	O
+that	O
+the	O
+corresponding	O
+orthologues	O
+from	O
+each	O
+Kingdom	O
+cluster	O
+separately	O
+.	O
+
+Comparative	O
+analysis	O
+of	O
+yeasts	O
+and	O
+filamentous	O
+fungi	O
+
+One	O
+striking	O
+difference	O
+in	O
+the	O
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+fungi	O
+is	O
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+those	O
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+have	O
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+,	O
+multi	O
+-	O
+cellular	O
+growth	O
+habit	O
+and	O
+those	O
+that	O
+grow	O
+as	O
+single	O
+yeast	B
+cells	O
+.	O
+
+There	O
+is	O
+some	O
+overlap	O
+between	O
+these	O
+two	O
+groups	O
+;	O
+because	O
+some	O
+fungi	O
+are	O
+dimorphic	O
+or	O
+even	O
+pleiomorphic	O
+,	O
+switching	O
+between	O
+different	O
+growth	O
+forms	O
+depending	O
+on	O
+environmental	O
+conditions	O
+or	O
+the	O
+stage	O
+of	O
+their	O
+life	O
+cycle	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+corn	B
+-	O
+smut	O
+fungus	O
+Ustilago	B
+maydis	I
+can	O
+exist	O
+saprophytically	O
+as	O
+haploid	O
+yeast	B
+-	O
+like	O
+cells	O
+,	O
+but	O
+needs	O
+to	O
+form	O
+a	O
+dikaryotic	O
+filamentous	O
+growth	O
+form	O
+in	O
+order	O
+to	O
+infect	O
+the	O
+host	O
+plant	O
+[	O
+23	O
+]	O
+.	O
+
+Generally	O
+the	O
+genomes	O
+of	O
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+fungi	O
+contain	O
+more	O
+protein	O
+-	O
+encoding	O
+genes	O
+(	O
+9	O
+,	O
+000	O
+-	O
+17	O
+,	O
+000	O
+)	O
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+those	O
+from	O
+unicellular	O
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+(	O
+5	O
+,	O
+000	O
+-	O
+7	O
+,	O
+000	O
+)	O
+,	O
+perhaps	O
+reflecting	O
+their	O
+greater	O
+morphological	O
+complexity	O
+and	O
+secondary	O
+metabolic	O
+capacity	O
+.	O
+
+U	B
+.	I
+maydis	I
+,	O
+however	O
+,	O
+has	O
+6	O
+,	O
+522	O
+protein	O
+encoding	O
+genes	O
+,	O
+perhaps	O
+reflecting	O
+its	O
+lack	O
+of	O
+extensive	O
+secondary	O
+metabolic	O
+pathways	O
+and	O
+its	O
+potential	O
+usefulness	O
+in	O
+defining	O
+the	O
+minimal	O
+gene	O
+sets	O
+associated	O
+with	O
+biotrophic	O
+growth	O
+[	O
+23	O
+]	O
+.	O
+
+The	O
+increase	O
+in	O
+proteome	O
+size	O
+in	O
+filamentous	O
+ascomycetes	O
+may	O
+be	O
+due	O
+to	O
+the	O
+expansion	O
+of	O
+certain	O
+gene	O
+families	O
+or	O
+the	O
+presence	O
+of	O
+novel	O
+genes	O
+that	O
+are	O
+essential	O
+for	O
+the	O
+filamentous	O
+lifestyle	O
+.	O
+
+For	O
+the	O
+purposes	O
+of	O
+this	O
+study	O
+,	O
+the	O
+filamentous	O
+fungi	O
+were	O
+defined	O
+as	O
+the	O
+filamentous	O
+ascomycetes	O
+(	O
+subphylum	O
+Pezizomycotina	O
+)	O
+,	O
+basidiomycetes	O
+and	O
+zygomycetes	O
+and	O
+the	O
+unicellular	O
+fungi	O
+were	O
+defined	O
+as	O
+the	O
+budding	O
+yeasts	O
+(	O
+order	O
+Saccharomycetales	O
+)	O
+,	O
+the	O
+archiascomycete	O
+Schizosaccharomyces	B
+pombe	I
+and	O
+the	O
+microsporidian	O
+fungus	O
+Encephalitozoon	B
+cuniculi	I
+.	O
+
+A	O
+total	O
+of	O
+37	O
+MCL	O
+clusters	O
+contained	O
+proteins	O
+from	O
+all	O
+species	O
+of	O
+filamentous	O
+fungi	O
+,	O
+but	O
+no	O
+species	O
+of	O
+unicellular	O
+fungi	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+eight	O
+of	O
+these	O
+clusters	O
+also	O
+contained	O
+proteins	O
+from	O
+both	O
+species	O
+of	O
+oomycete	O
+represented	O
+in	O
+e	O
+-	O
+Fungi	O
+.	O
+
+The	O
+filamentous	O
+-	O
+fungal	O
+specific	O
+clusters	O
+included	O
+a	O
+number	O
+of	O
+proteins	O
+that	O
+are	O
+involved	O
+in	O
+cytoskeletal	O
+rearrangements	O
+(	O
+dedicator	O
+of	O
+cytokinesis	O
+protein	O
+,	O
+integrin	O
+beta	O
+-	O
+1	O
+-	O
+binding	O
+protein	O
+,	O
+dynactin	O
+p62	O
+family	O
+,	O
+dynein	O
+light	O
+intermediate	O
+chain	O
+2	O
+)	O
+,	O
+it	O
+seems	O
+likely	O
+that	O
+these	O
+are	O
+required	O
+for	O
+the	O
+complex	O
+morphological	O
+changes	O
+that	O
+filamentous	O
+fungi	O
+undergo	O
+during	O
+their	O
+lifecycle	O
+and	O
+the	O
+production	O
+of	O
+differentiated	O
+cells	O
+,	O
+such	O
+as	O
+spores	O
+,	O
+fruiting	O
+bodies	O
+and	O
+infection	O
+structures	O
+.	O
+
+The	O
+results	O
+also	O
+suggest	O
+that	O
+filamentous	O
+fungal	O
+species	O
+make	O
+a	O
+greater	O
+use	O
+of	O
+lipids	O
+as	O
+signalling	O
+molecules	O
+than	O
+yeast	B
+species	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+occurrence	O
+of	O
+filamentous	O
+fungal	O
+-	O
+specific	O
+clusters	O
+representing	O
+two	O
+groups	O
+of	O
+lysophospholipases	O
+,	O
+as	O
+well	O
+as	O
+ceramidases	O
+that	O
+are	O
+involved	O
+in	O
+sphingolipid	O
+signalling	O
+[	O
+35	O
+]	O
+and	O
+linoleate	O
+diol	O
+synthases	O
+that	O
+can	O
+catalyse	O
+the	O
+formation	O
+of	O
+leukotrienes	O
+[	O
+36	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+one	O
+of	O
+the	O
+products	O
+of	O
+linoleate	O
+diol	O
+synthase	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+a	O
+sporulation	O
+hormone	O
+in	O
+Aspergillus	B
+nidulans	I
+[	O
+37	O
+]	O
+.	O
+
+There	O
+is	O
+also	O
+a	O
+cluster	O
+that	O
+represents	O
+homologues	O
+of	O
+a	O
+novel	O
+human	B
+gene	O
+(	O
+LRP16	O
+)	O
+that	O
+acts	O
+downstream	O
+of	O
+a	O
+steroid	O
+receptor	O
+and	O
+promotes	O
+cell	O
+proliferation	O
+[	O
+38	O
+]	O
+.	O
+
+Two	O
+clusters	O
+of	O
+filamentous	O
+fungal	O
+-	O
+specific	O
+proteins	O
+represent	O
+enzymes	O
+involved	O
+in	O
+molypterin	O
+biosynthesis	O
+(	O
+MCL2420	O
+,	O
+MCL2581	O
+)	O
+.	O
+
+Molypterin	O
+is	O
+a	O
+molybdenum	O
+-	O
+containing	O
+co	O
+-	O
+factor	O
+for	O
+nitrate	O
+reductase	O
+,	O
+an	O
+enzyme	O
+that	O
+is	O
+known	O
+to	O
+be	O
+absent	O
+from	O
+the	O
+species	O
+of	O
+yeast	B
+used	O
+in	O
+this	O
+study	O
+[	O
+39	O
+]	O
+.	O
+
+Both	O
+these	O
+clusters	O
+are	O
+also	O
+found	O
+in	O
+oomycetes	O
+.	O
+
+There	O
+are	O
+other	O
+clusters	O
+representing	O
+proteins	O
+important	O
+for	O
+activities	O
+specific	O
+to	O
+filamentous	O
+fungi	O
+,	O
+such	O
+as	O
+homologues	O
+of	O
+Pro11	O
+(	O
+striatin	O
+)	O
+which	O
+regulates	O
+fruiting	O
+body	O
+formation	O
+in	O
+Sordaria	B
+macrospora	I
+[	O
+40	O
+]	O
+,	O
+the	O
+vegetatible	O
+incompatibility	O
+protein	O
+HET	O
+-	O
+E	O
+-	O
+1	O
+,	O
+which	O
+prevents	O
+the	O
+formation	O
+of	O
+heterokaryons	O
+between	O
+incompatible	O
+fungal	O
+strains	O
+in	O
+Podospora	B
+anserina	I
+[	O
+41	O
+]	O
+,	O
+anucleate	O
+primary	O
+sterigmata	O
+protein	O
+A	O
+from	O
+Aspergillus	B
+nidulans	I
+,	O
+which	O
+is	O
+essential	O
+for	O
+nuclear	O
+migration	O
+and	O
+conidiophore	O
+development	O
+[	O
+42	O
+]	O
+and	O
+cytochrome	O
+P450	O
+and	O
+polyketide	O
+synthase	O
+-	O
+encoding	O
+genes	O
+,	O
+both	O
+of	O
+which	O
+are	O
+involved	O
+in	O
+a	O
+number	O
+of	O
+secondary	O
+metabolic	O
+pathways	O
+including	O
+toxin	O
+biosynthesis	O
+[	O
+43	O
+]	O
+.	O
+
+Pathogenicity	O
+-	O
+associated	O
+gene	O
+functions	O
+in	O
+fungi	O
+
+As	O
+the	O
+selected	O
+set	O
+of	O
+fungi	O
+includes	O
+both	O
+saprotrophic	O
+and	O
+pathogenic	O
+species	O
+,	O
+this	O
+allows	O
+us	O
+to	O
+compare	O
+the	O
+gene	O
+inventories	O
+of	O
+phytopathogenic	O
+and	O
+closely	O
+related	O
+non	O
+-	O
+pathogenic	O
+fungi	O
+to	O
+look	O
+for	O
+genes	O
+that	O
+are	O
+unique	O
+to	O
+phytopathogens	O
+.	O
+
+Analysis	O
+of	O
+MCL	O
+clusters	O
+showed	O
+that	O
+there	O
+were	O
+no	O
+clusters	O
+that	O
+contained	O
+proteins	O
+from	O
+all	O
+species	O
+of	O
+fungal	O
+phytopathogen	O
+in	O
+e	O
+-	O
+Fungi	O
+(	O
+namely	O
+B	B
+.	I
+cinerea	I
+,	O
+Eremothecium	B
+gossypii	I
+,	O
+G	B
+.	I
+zeae	I
+,	O
+M	B
+.	I
+grisea	I
+,	O
+S	B
+.	I
+sclerotiorum	I
+,	O
+S	B
+.	I
+nodorum	I
+and	O
+U	B
+.	I
+maydis	I
+)	O
+but	O
+did	O
+not	O
+contain	O
+proteins	O
+from	O
+non	O
+-	O
+pathogenic	O
+species	O
+.	O
+
+There	O
+were	O
+,	O
+however	O
+,	O
+four	O
+clusters	O
+that	O
+were	O
+exclusive	O
+to	O
+filamentous	O
+ascomycete	O
+phytopathogens	O
+(	O
+namely	O
+B	B
+.	I
+cinerea	I
+,	O
+G	B
+.	I
+zeae	I
+,	O
+M	B
+.	I
+grisea	I
+,	O
+S	B
+.	I
+sclerotiorum	I
+,	O
+S	B
+.	I
+nodorum	I
+as	O
+shown	O
+in	O
+Table	O
+3	O
+)	O
+.	O
+
+Significantly	O
+,	O
+none	O
+of	O
+the	O
+members	O
+of	O
+these	O
+clusters	O
+had	O
+homology	O
+to	O
+any	O
+known	O
+proteins	O
+or	O
+contained	O
+motifs	O
+from	O
+the	O
+Pfam	O
+database	O
+[	O
+44	O
+]	O
+,	O
+so	O
+we	O
+were	O
+unable	O
+to	O
+predict	O
+their	O
+function	O
+,	O
+although	O
+two	O
+of	O
+the	O
+clusters	O
+(	O
+MCL4854	O
+and	O
+MCL8229	O
+)	O
+consisted	O
+entirely	O
+of	O
+proteins	O
+that	O
+were	O
+predicted	O
+to	O
+be	O
+secreted	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+observations	O
+indicate	O
+that	O
+a	O
+battery	O
+of	O
+completely	O
+novel	O
+secreted	O
+proteins	O
+may	O
+be	O
+associated	O
+with	O
+ascomycete	O
+fungal	O
+pathogens	O
+.	O
+
+Pathogenicity	O
+factors	O
+have	O
+been	O
+defined	O
+as	O
+genes	O
+that	O
+are	O
+essential	O
+for	O
+successful	O
+completion	O
+of	O
+the	O
+pathogen	O
+lifecycle	O
+but	O
+dispensable	O
+for	O
+saprophytic	O
+growth	O
+[	O
+4	O
+]	O
+.	O
+
+This	O
+is	O
+an	O
+experimental	O
+definition	O
+based	O
+on	O
+whether	O
+null	O
+mutations	O
+of	O
+a	O
+given	O
+gene	O
+reduce	O
+the	O
+virulence	O
+of	O
+the	O
+pathogen	O
+on	O
+its	O
+host	O
+.	O
+
+We	O
+wished	O
+to	O
+ascertain	O
+whether	O
+homologues	O
+of	O
+previously	O
+characterised	O
+and	O
+experimentally	O
+-	O
+validated	O
+pathogenicity	O
+factors	O
+were	O
+limited	O
+to	O
+the	O
+genomes	O
+of	O
+pathogenic	O
+species	O
+.	O
+
+A	O
+search	O
+was	O
+therefore	O
+made	O
+for	O
+pathogenicity	O
+factors	O
+that	O
+have	O
+been	O
+identified	O
+experimentally	O
+for	O
+the	O
+species	O
+of	O
+phytopathogens	O
+represented	O
+in	O
+e	O
+-	O
+Fungi	O
+using	O
+PHI	O
+-	O
+base	O
+,	O
+the	O
+plant	O
+-	O
+host	O
+interaction	O
+database	O
+[	O
+45	O
+]	O
+.	O
+
+The	O
+matching	O
+locus	O
+was	O
+identified	O
+for	O
+each	O
+pathogenicity	O
+factor	O
+in	O
+the	O
+corresponding	O
+genome	O
+sequence	O
+by	O
+comparing	O
+a	O
+published	O
+protein	O
+sequence	O
+with	O
+sets	O
+of	O
+predicted	O
+proteins	O
+for	O
+each	O
+genome	O
+using	O
+BLASTP	O
+.	O
+
+This	O
+produced	O
+a	O
+list	O
+of	O
+105	O
+pathogenicity	O
+factors	O
+,	O
+although	O
+corresponding	O
+loci	O
+could	O
+not	O
+be	O
+found	O
+in	O
+genome	O
+sequences	O
+for	O
+all	O
+the	O
+published	O
+genes	O
+(	O
+see	O
+Table	O
+S5	O
+)	O
+.	O
+
+MCL	O
+clusters	O
+containing	O
+these	O
+proteins	O
+were	O
+identified	O
+(	O
+76	O
+unique	O
+clusters	O
+)	O
+and	O
+the	O
+species	O
+distribution	O
+of	O
+members	O
+of	O
+these	O
+clusters	O
+analysed	O
+.	O
+
+In	O
+total	O
+,	O
+29	O
+of	O
+the	O
+MCL	O
+clusters	O
+contained	O
+pathogenicity	O
+factors	O
+with	O
+members	O
+from	O
+at	O
+least	O
+34	O
+of	O
+the	O
+36	O
+species	O
+represented	O
+in	O
+e	O
+-	O
+Fungi	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+Not	O
+surprisingly	O
+,	O
+many	O
+of	O
+these	O
+clusters	O
+contain	O
+conserved	O
+components	O
+of	O
+signalling	O
+pathways	O
+such	O
+as	O
+protein	O
+kinases	O
+,	O
+adenylate	O
+cyclases	O
+,	O
+G	O
+-	O
+proteins	O
+and	O
+cell	O
+cycle	O
+regulators	O
+.	O
+
+Cellular	O
+morphogenesis	O
+is	O
+known	O
+to	O
+be	O
+important	O
+for	O
+infection	O
+of	O
+the	O
+host	O
+plant	O
+by	O
+many	O
+phytopathogens	O
+,	O
+for	O
+example	O
+,	O
+in	O
+appressorium	O
+formation	O
+in	O
+Magnaporthe	B
+grisea	I
+[	O
+46	O
+]	O
+or	O
+the	O
+switch	O
+in	O
+the	O
+growth	O
+form	O
+of	O
+Ustilago	B
+maydis	I
+from	O
+yeast	B
+-	O
+like	O
+growth	O
+to	O
+filamentous	O
+invasive	O
+growth	O
+[	O
+47	O
+]	O
+.	O
+
+Links	O
+between	O
+successful	O
+plant	O
+infection	O
+and	O
+cell	O
+cycle	O
+control	O
+have	O
+also	O
+been	O
+demonstrated	O
+[	O
+48	O
+]	O
+.	O
+
+It	O
+seems	O
+likely	O
+that	O
+conserved	O
+signalling	O
+pathways	O
+that	O
+control	O
+activities	O
+,	O
+such	O
+as	O
+mating	O
+and	O
+morphogenesis	O
+in	O
+all	O
+fungi	O
+,	O
+have	O
+evolved	O
+to	O
+control	O
+processes	O
+essential	O
+for	O
+pathogencity	O
+in	O
+phytopathogens	O
+.	O
+
+Other	O
+conserved	O
+pathogenicity	O
+factors	O
+encode	O
+enzymes	O
+of	O
+metabolic	O
+pathways	O
+that	O
+are	O
+present	O
+in	O
+nearly	O
+all	O
+fungi	O
+,	O
+but	O
+seem	O
+to	O
+be	O
+important	O
+for	O
+the	O
+life	O
+cycle	O
+of	O
+particular	O
+pathogenic	O
+species	O
+,	O
+for	O
+example	O
+,	O
+enzymes	O
+involved	O
+in	O
+beta	O
+-	O
+oxidation	O
+of	O
+fatty	O
+acids	O
+,	O
+the	O
+glyoxylate	O
+shunt	O
+,	O
+amino	O
+acid	O
+metabolism	O
+and	O
+the	O
+utilisation	O
+of	O
+stored	O
+sugars	O
+.	O
+
+When	O
+considered	O
+together	O
+,	O
+this	O
+may	O
+indicate	O
+that	O
+nutritional	O
+conditions	O
+which	O
+fungi	O
+encounter	O
+when	O
+invading	O
+host	O
+plant	O
+tissue	O
+require	O
+mobilisation	O
+of	O
+stored	O
+lipids	O
+prior	O
+to	O
+nutrition	O
+being	O
+extracted	O
+from	O
+the	O
+host	O
+plant	O
+.	O
+
+Seventeen	O
+of	O
+the	O
+MCL	O
+clusters	O
+containing	O
+pathogenicity	O
+factors	O
+were	O
+specific	O
+to	O
+filamentous	O
+ascomycetes	O
+(	O
+Table	O
+5	O
+)	O
+.	O
+
+These	O
+include	O
+a	O
+number	O
+of	O
+enzymes	O
+involved	O
+in	O
+secondary	O
+metabolism	O
+,	O
+such	O
+as	O
+those	O
+involved	O
+in	O
+the	O
+synthesis	O
+of	O
+the	O
+fungal	O
+toxin	O
+trichothecene	O
+in	O
+G	B
+.	I
+zeae	I
+[	O
+43	O
+]	O
+and	O
+those	O
+involved	O
+in	O
+melanin	O
+biosynthesis	O
+[	O
+49	O
+]	O
+,	O
+as	O
+well	O
+as	O
+structural	O
+proteins	O
+,	O
+some	O
+of	O
+which	O
+are	O
+components	O
+of	O
+differentiated	O
+cell	O
+types	O
+not	O
+seen	O
+in	O
+yeasts	O
+,	O
+for	O
+example	O
+,	O
+hydrophobins	O
+which	O
+are	O
+components	O
+of	O
+aerial	O
+structures	O
+such	O
+as	O
+fruiting	O
+bodies	O
+[	O
+50	O
+]	O
+but	O
+are	O
+also	O
+involved	O
+in	O
+pathogenicity	O
+[	O
+16	O
+]	O
+.	O
+
+There	O
+also	O
+seems	O
+to	O
+be	O
+a	O
+number	O
+of	O
+filamentous	O
+ascomycete	O
+specific	O
+receptor	O
+proteins	O
+(	O
+transducin	O
+beta	O
+-	O
+subunit	O
+,	O
+G	O
+-	O
+protein	O
+coupled	O
+receptor	O
+,	O
+tetraspanins	O
+)	O
+that	O
+have	O
+evolved	O
+in	O
+pathogens	O
+to	O
+be	O
+used	O
+in	O
+sensing	O
+environmental	O
+cues	O
+that	O
+are	O
+essential	O
+for	O
+successful	O
+infection	O
+of	O
+the	O
+host	O
+[	O
+51	O
+]	O
+.	O
+
+The	O
+Woronin	O
+body	O
+is	O
+a	O
+structure	O
+found	O
+only	O
+in	O
+filamentous	O
+ascomycetes	O
+,	O
+and	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+essential	O
+for	O
+pathogenicity	O
+in	O
+M	B
+.	I
+grisea	I
+[	O
+52	O
+]	O
+.	O
+
+A	O
+major	O
+constituent	O
+of	O
+the	O
+woronin	O
+body	O
+,	O
+encoded	O
+by	O
+MVP1	O
+,	O
+is	O
+a	O
+pathogenicity	O
+factor	O
+for	O
+M	B
+.	I
+grisea	I
+,	O
+but	O
+also	O
+has	O
+homologues	O
+in	O
+nearly	O
+all	O
+species	O
+of	O
+filamentous	O
+ascomycetes	O
+.	O
+
+Two	O
+proteins	O
+that	O
+were	O
+initially	O
+discovered	O
+as	O
+being	O
+highly	O
+expressed	O
+in	O
+the	O
+appressoria	O
+of	O
+M	B
+.	I
+grisea	I
+and	O
+essential	O
+for	O
+pathogenicity	O
+(	O
+Mas1	O
+and	O
+Mas3	O
+)	O
+[	O
+53	O
+]	O
+also	O
+have	O
+homologues	O
+in	O
+a	O
+number	O
+of	O
+species	O
+of	O
+filamentous	O
+fungi	O
+(	O
+Table	O
+5	O
+)	O
+.	O
+
+Thus	O
+,	O
+many	O
+innovations	O
+that	O
+have	O
+allowed	O
+filamentous	O
+ascomycetes	O
+to	O
+have	O
+a	O
+more	O
+complex	O
+morphology	O
+than	O
+unicellular	O
+yeasts	O
+have	O
+also	O
+evolved	O
+to	O
+be	O
+essential	O
+for	O
+plant	O
+infection	O
+by	O
+phytopathogenic	O
+species	O
+.	O
+
+Interestingly	O
+,	O
+none	O
+of	O
+the	O
+MCL	O
+clusters	O
+containing	O
+known	O
+pathogenicity	O
+factors	O
+contained	O
+members	O
+only	O
+from	O
+phytopathogenic	O
+fungi	O
+,	O
+apart	O
+from	O
+those	O
+that	O
+were	O
+restricted	O
+to	O
+just	O
+one	O
+species	O
+.	O
+
+These	O
+are	O
+therefore	O
+likely	O
+to	O
+represent	O
+highly	O
+-	O
+specialised	O
+proteins	O
+that	O
+have	O
+evolved	O
+for	O
+the	O
+specific	O
+lifecycle	O
+of	O
+just	O
+one	O
+species	O
+of	O
+phytopathogen	O
+,	O
+for	O
+example	O
+the	O
+Pwl	O
+proteins	O
+involved	O
+in	O
+determining	O
+host	O
+range	O
+of	O
+different	O
+strains	O
+of	O
+M	B
+.	I
+grisea	I
+[	O
+54	O
+]	O
+.	O
+
+Two	O
+of	O
+the	O
+proteins	O
+specific	O
+to	O
+M	B
+.	I
+grisea	I
+,	O
+the	O
+metallothionein	O
+Mmt1	O
+[	O
+55	O
+]	O
+and	O
+the	O
+hydrophobin	O
+Mpg1	O
+[	O
+56	O
+]	O
+are	O
+small	O
+polypeptides	O
+and	O
+are	O
+members	O
+of	O
+highly	O
+divergent	O
+gene	O
+families	O
+,	O
+other	O
+members	O
+of	O
+which	O
+do	O
+not	O
+cluster	O
+together	O
+using	O
+BLASTP	O
+.	O
+
+Comparative	O
+analysis	O
+of	O
+plant	O
+-	O
+pathogenic	O
+and	O
+saprotrophic	O
+filamentous	O
+ascomycetes	O
+
+Based	O
+on	O
+the	O
+analysis	O
+reported	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+in	O
+general	O
+there	O
+are	O
+a	O
+large	O
+number	O
+of	O
+differences	O
+in	O
+gene	O
+inventories	O
+between	O
+filamentous	O
+and	O
+yeast	B
+-	O
+like	O
+fungi	O
+.	O
+
+Therefore	O
+,	O
+in	O
+order	O
+to	O
+compare	O
+the	O
+genomes	O
+of	O
+phytopathogens	O
+and	O
+saprotrophs	O
+,	O
+we	O
+focused	O
+on	O
+filamentous	O
+ascomycetes	O
+in	O
+order	O
+to	O
+resolve	O
+in	O
+greater	O
+detail	O
+the	O
+distinct	O
+differences	O
+in	O
+gene	O
+sets	O
+between	O
+these	O
+two	O
+ecologically	O
+separate	O
+groups	O
+of	O
+fungi	O
+.	O
+
+In	O
+this	O
+way	O
+differences	O
+due	O
+to	O
+phylogeny	O
+between	O
+the	O
+species	O
+would	O
+be	O
+minimised	O
+.	O
+
+We	O
+compared	O
+the	O
+gene	O
+inventories	O
+of	O
+the	O
+phytopathogens	O
+B	B
+.	I
+cinerea	I
+,	O
+G	B
+.	I
+zeae	I
+,	O
+M	B
+.	I
+grisea	I
+,	O
+S	B
+.	I
+sclerotiorum	I
+,	O
+S	B
+.	I
+nodorum	I
+with	O
+the	O
+non	O
+-	O
+pathogens	O
+Aspergillus	B
+nidulans	I
+,	O
+Chaetomium	B
+globosum	I
+,	O
+Neurospora	B
+crassa	I
+and	O
+Trichoderma	B
+reesei	I
+.	O
+
+Phylogenetic	O
+analysis	O
+suggests	O
+that	O
+the	O
+phytopathogenic	O
+species	O
+do	O
+not	O
+form	O
+a	O
+separate	O
+clade	O
+from	O
+the	O
+pathogenic	O
+species	O
+(	O
+Figure	O
+1	O
+)	O
+,	O
+[	O
+3	O
+]	O
+and	O
+we	O
+assumed	O
+that	O
+differences	O
+in	O
+gene	O
+inventory	O
+should	O
+therefore	O
+reflect	O
+lifestyle	O
+rather	O
+than	O
+evolutionary	O
+distance	O
+.	O
+
+In	O
+order	O
+for	O
+such	O
+a	O
+comparison	O
+to	O
+be	O
+considered	O
+valid	O
+,	O
+the	O
+completeness	O
+and	O
+quality	O
+of	O
+the	O
+fungal	O
+genome	O
+sequences	O
+used	O
+should	O
+,	O
+however	O
+,	O
+also	O
+be	O
+comparable	O
+.	O
+
+Table	O
+S6	O
+summarises	O
+the	O
+available	O
+data	O
+about	O
+genome	O
+sequence	O
+coverage	O
+,	O
+genome	O
+size	O
+and	O
+the	O
+number	O
+of	O
+predicted	O
+proteins	O
+for	O
+each	O
+species	O
+.	O
+
+This	O
+shows	O
+that	O
+the	O
+genome	O
+coverage	O
+is	O
+greater	O
+than	O
+5x	O
+and	O
+the	O
+number	O
+of	O
+predicted	O
+proteins	O
+in	O
+the	O
+range	O
+of	O
+10	O
+,	O
+000	O
+-	O
+16	O
+,	O
+000	O
+for	O
+all	O
+genomes	O
+used	O
+,	O
+suggesting	O
+a	O
+high	O
+level	O
+of	O
+equivalence	O
+between	O
+species	O
+with	O
+regard	O
+to	O
+sequence	O
+quality	O
+.	O
+
+From	O
+our	O
+work	O
+it	O
+seems	O
+unlikely	O
+that	O
+there	O
+are	O
+pathogenicity	O
+factors	O
+conserved	O
+in	O
+,	O
+and	O
+specific	O
+to	O
+,	O
+all	O
+species	O
+of	O
+phytopathogen	O
+.	O
+
+It	O
+may	O
+,	O
+for	O
+instance	O
+,	O
+be	O
+the	O
+case	O
+that	O
+differences	O
+in	O
+the	O
+gene	O
+inventories	O
+are	O
+due	O
+to	O
+the	O
+expansion	O
+of	O
+certain	O
+gene	O
+families	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogenic	O
+species	O
+associated	O
+with	O
+functions	O
+necessary	O
+for	O
+pathogenesis	O
+.	O
+
+To	O
+define	O
+protein	O
+families	O
+,	O
+we	O
+used	O
+the	O
+Pfam	O
+database	O
+which	O
+contains	O
+protein	O
+family	O
+models	O
+based	O
+on	O
+Hidden	O
+Markov	O
+Models	O
+[	O
+44	O
+]	O
+,	O
+[	O
+57	O
+]	O
+.	O
+
+Sets	O
+of	O
+predicted	O
+proteins	O
+for	O
+each	O
+fungal	O
+species	O
+in	O
+e	O
+-	O
+Fungi	O
+were	O
+analysed	O
+for	O
+the	O
+occurrence	O
+of	O
+Pfam	O
+motifs	O
+and	O
+the	O
+number	O
+of	O
+proteins	O
+containing	O
+each	O
+domain	O
+across	O
+fungal	O
+species	O
+ascertained	O
+.	O
+
+The	O
+sets	O
+of	O
+predicted	O
+protein	O
+sequences	O
+used	O
+in	O
+this	O
+study	O
+have	O
+been	O
+automatically	O
+predicted	O
+as	O
+part	O
+of	O
+each	O
+individual	O
+genome	O
+project	O
+and	O
+are	O
+likely	O
+to	O
+contain	O
+a	O
+number	O
+of	O
+artefactual	O
+sequences	O
+.	O
+
+The	O
+use	O
+of	O
+Pfam	O
+motifs	O
+to	O
+define	O
+gene	O
+families	O
+in	O
+this	O
+study	O
+reduces	O
+the	O
+likelihood	O
+of	O
+such	O
+sequences	O
+affecting	O
+the	O
+data	O
+,	O
+since	O
+Pfam	O
+motifs	O
+are	O
+based	O
+on	O
+multiple	O
+sequence	O
+alignments	O
+of	O
+well	O
+-	O
+studied	O
+proteins	O
+.	O
+
+A	O
+small	O
+number	O
+of	O
+Pfam	O
+motifs	O
+were	O
+not	O
+found	O
+in	O
+the	O
+proteomes	O
+of	O
+the	O
+filamentous	O
+ascomycete	O
+non	O
+-	O
+pathogens	O
+,	O
+but	O
+were	O
+found	O
+in	O
+the	O
+proteomes	O
+of	O
+at	O
+least	O
+three	O
+species	O
+of	O
+filamentous	O
+ascomycete	O
+phytopathogens	O
+(	O
+Table	O
+6	O
+)	O
+.	O
+
+These	O
+include	O
+the	O
+Cas1p	O
+-	O
+like	O
+motif	O
+(	O
+PF07779	O
+)	O
+,	O
+found	O
+in	O
+4	O
+species	O
+of	O
+phytopathogen	O
+,	O
+including	O
+five	O
+copies	O
+in	O
+G	B
+.	I
+zeae	I
+,	O
+and	O
+the	O
+Yeast	B
+cell	O
+wall	O
+synthesis	O
+protein	O
+KRE9	O
+/	O
+KNH1	O
+motif	O
+(	O
+PF05390	O
+)	O
+,	O
+which	O
+was	O
+found	O
+in	O
+three	O
+species	O
+of	O
+phytopathogen	O
+.	O
+
+Cas1p	O
+is	O
+a	O
+membrane	O
+protein	O
+necessary	O
+for	O
+the	O
+O	O
+-	O
+acetylation	O
+of	O
+the	O
+capsular	O
+polysaccharide	O
+of	O
+the	O
+basidiomycete	O
+animal	O
+pathogen	O
+Cryptococcus	B
+neoformans	I
+[	O
+58	O
+]	O
+.	O
+
+KRE9	O
+and	O
+KNH1	O
+are	O
+involved	O
+in	O
+the	O
+synthesis	O
+of	O
+cell	O
+surface	O
+polysaccharides	O
+in	O
+S	B
+.	I
+cerevisiae	I
+[	O
+59	O
+]	O
+.	O
+
+Taken	O
+together	O
+this	O
+suggests	O
+that	O
+synthesis	O
+of	O
+cell	O
+surface	O
+polysaccharides	O
+is	O
+important	O
+for	O
+phytopathogens	O
+,	O
+perhaps	O
+helping	O
+to	O
+shroud	O
+the	O
+fungus	O
+from	O
+plant	O
+defences	O
+.	O
+
+The	O
+function	O
+of	O
+the	O
+YDG	O
+/	O
+SRA	O
+domain	O
+motif	O
+(	O
+PF02182	O
+)	O
+is	O
+unknown	O
+,	O
+but	O
+is	O
+found	O
+in	O
+a	O
+novel	O
+mouse	B
+cell	O
+proliferation	O
+protein	O
+Np95	O
+,	O
+in	O
+which	O
+the	O
+domain	O
+is	O
+important	O
+both	O
+for	O
+the	O
+interaction	O
+with	O
+histones	O
+and	O
+for	O
+chromatin	O
+binding	O
+in	O
+vivo	O
+[	O
+60	O
+]	O
+.	O
+
+As	O
+well	O
+as	O
+domains	O
+of	O
+unknown	O
+function	O
+,	O
+the	O
+list	O
+of	O
+phytopathogen	O
+-	O
+specific	O
+Pfam	O
+motifs	O
+includes	O
+Allophanate	O
+hydrolase	O
+(	O
+PF02682	O
+)	O
+which	O
+is	O
+found	O
+in	O
+an	O
+enzyme	O
+involved	O
+in	O
+the	O
+ATP	O
+-	O
+dependent	O
+urea	O
+degradation	O
+pathway	O
+[	O
+61	O
+]	O
+,	O
+a	O
+peptidase	O
+motif	O
+,	O
+an	O
+opioid	O
+growth	O
+receptor	O
+motif	O
+(	O
+PF04664	O
+)	O
+and	O
+Mnd1	O
+(	O
+PF03962	O
+)	O
+,	O
+which	O
+is	O
+involved	O
+in	O
+recombination	O
+and	O
+meiotic	O
+nuclear	O
+division	O
+[	O
+62	O
+]	O
+.	O
+
+To	O
+detect	O
+potential	O
+gene	O
+family	O
+expansion	O
+,	O
+we	O
+decided	O
+to	O
+identify	O
+Pfam	O
+motifs	O
+that	O
+were	O
+present	O
+in	O
+both	O
+phytopathogenic	O
+and	O
+non	O
+-	O
+pathogenic	O
+species	O
+of	O
+filamentous	O
+ascomycetes	O
+,	O
+but	O
+that	O
+were	O
+more	O
+common	O
+in	O
+the	O
+genomes	O
+of	O
+the	O
+former	O
+.	O
+
+The	O
+Pfam	O
+motifs	O
+were	O
+ranked	O
+on	O
+the	O
+ratio	O
+of	O
+the	O
+mean	O
+number	O
+of	O
+proteins	O
+containing	O
+each	O
+motif	O
+in	O
+phytopathogens	O
+,	O
+when	O
+compared	O
+to	O
+non	O
+-	O
+pathogens	O
+(	O
+Table	O
+7	O
+)	O
+.	O
+
+The	O
+tables	O
+only	O
+show	O
+ratios	O
+of	O
+greater	O
+than	O
+or	O
+equal	O
+to	O
+2	O
+.	O
+5	O
+.	O
+
+Pfam	O
+motifs	O
+that	O
+were	O
+more	O
+common	O
+in	O
+the	O
+proteomes	O
+of	O
+pathogens	O
+,	O
+include	O
+some	O
+found	O
+in	O
+enzymes	O
+involved	O
+in	O
+secondary	O
+metabolic	O
+pathways	O
+.	O
+
+These	O
+include	O
+novel	O
+enzymes	O
+that	O
+have	O
+only	O
+previously	O
+been	O
+studied	O
+in	O
+non	O
+-	O
+fungal	O
+species	O
+,	O
+such	O
+as	O
+the	O
+chalcone	O
+synthases	O
+;	O
+type	O
+III	O
+polyketide	O
+synthases	O
+involved	O
+in	O
+the	O
+biosynthesis	O
+of	O
+flavonoids	O
+in	O
+plants	O
+[	O
+63	O
+]	O
+and	O
+lipoxygenases	O
+;	O
+components	O
+of	O
+metabolic	O
+pathways	O
+resulting	O
+in	O
+the	O
+synthesis	O
+of	O
+physiologically	O
+-	O
+active	O
+compounds	O
+such	O
+as	O
+eicosanoids	O
+in	O
+mammals	O
+[	O
+64	O
+]	O
+and	O
+jasmonic	O
+acid	O
+in	O
+plants	O
+[	O
+65	O
+]	O
+as	O
+well	O
+as	O
+antibiotic	O
+synthesis	O
+monooxygenases	O
+.	O
+
+It	O
+seems	O
+likely	O
+that	O
+secondary	O
+metabolism	O
+is	O
+essential	O
+in	O
+phytopathogenic	O
+species	O
+for	O
+the	O
+synthesis	O
+of	O
+mycotoxins	O
+,	O
+antibiotics	O
+,	O
+siderophores	O
+and	O
+pigments	O
+[	O
+66	O
+]	O
+,	O
+but	O
+it	O
+may	O
+also	O
+offer	O
+fungal	O
+pathogens	O
+a	O
+distinct	O
+alternative	O
+means	O
+of	O
+perturbing	O
+host	O
+metabolism	O
+,	O
+cell	O
+signalling	O
+or	O
+plant	O
+defence	O
+,	O
+in	O
+contrast	O
+to	O
+bacterial	O
+pathogens	O
+that	O
+rely	O
+on	O
+protein	O
+secretion	O
+to	O
+achieve	O
+this	O
+.	O
+
+There	O
+also	O
+seems	O
+to	O
+be	O
+number	O
+of	O
+protease	O
+and	O
+peptidase	O
+domains	O
+that	O
+are	O
+more	O
+common	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogens	O
+as	O
+well	O
+as	O
+domains	O
+from	O
+two	O
+classes	O
+of	O
+cell	O
+-	O
+wall	O
+degrading	O
+enzymes	O
+:	O
+namely	O
+cutinase	O
+(	O
+PF01083	O
+)	O
+and	O
+Glycosyl	O
+hydrolase	O
+family	O
+53	O
+(	O
+PF07745	O
+)	O
+which	O
+is	O
+found	O
+in	O
+arabinogalactan	O
+endo	O
+-	O
+1	O
+,	O
+4	O
+-	O
+beta	O
+-	O
+galactosidases	O
+that	O
+hydrolyze	O
+the	O
+galactan	O
+side	O
+chains	O
+that	O
+form	O
+part	O
+of	O
+the	O
+complex	O
+carbohydrate	O
+structure	O
+of	O
+pectin	O
+[	O
+67	O
+]	O
+.	O
+
+Two	O
+other	O
+domains	O
+found	O
+in	O
+enzymes	O
+involved	O
+in	O
+pectin	O
+degradation	O
+,	O
+pectinesterase	O
+(	O
+PF01095	O
+)	O
+and	O
+Glycosyl	O
+hydrolases	O
+family	O
+28	O
+(	O
+PF00295	O
+)	O
+are	O
+both	O
+more	O
+than	O
+twice	O
+as	O
+common	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogens	O
+than	O
+saprotrophs	O
+.	O
+
+In	O
+contrast	O
+,	O
+domains	O
+found	O
+in	O
+cellulases	O
+have	O
+fairly	O
+equal	O
+distribution	O
+between	O
+the	O
+proteomes	O
+of	O
+phytopathogens	O
+and	O
+non	O
+-	O
+pathogens	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Therefore	O
+,	O
+for	O
+phytopathogens	O
+the	O
+most	O
+essential	O
+enzymes	O
+for	O
+pathogenesis	O
+may	O
+well	O
+be	O
+those	O
+that	O
+allow	O
+the	O
+fungus	O
+to	O
+penetrate	O
+the	O
+protective	O
+cutin	O
+layer	O
+of	O
+the	O
+plant	O
+epidermis	O
+and	O
+disrupt	O
+the	O
+pectin	O
+matrix	O
+of	O
+the	O
+plant	O
+cell	O
+wall	O
+in	O
+which	O
+cellulose	O
+fibrils	O
+are	O
+embedded	O
+.	O
+
+Pectin	O
+-	O
+degrading	O
+enzymes	O
+have	O
+already	O
+been	O
+shown	O
+to	O
+be	O
+pathogenicity	O
+factors	O
+in	O
+a	O
+number	O
+of	O
+fungi	O
+[	O
+68	O
+]	O
+.	O
+
+NPP1	O
+motifs	O
+are	O
+characteristic	O
+of	O
+a	O
+group	O
+of	O
+proteins	O
+called	O
+NLPs	O
+(	O
+Nep1	O
+-	O
+like	O
+proteins	O
+)	O
+that	O
+trigger	O
+defence	O
+responses	O
+,	O
+necrosis	O
+and	O
+cell	O
+death	O
+in	O
+plants	O
+and	O
+may	O
+act	O
+as	O
+virulence	O
+factors	O
+[	O
+69	O
+]	O
+.	O
+
+The	O
+NLPs	O
+are	O
+more	O
+common	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogenic	O
+,	O
+when	O
+compared	O
+to	O
+non	O
+-	O
+pathogenic	O
+ascomycetes	O
+,	O
+but	O
+are	O
+even	O
+more	O
+numerous	O
+in	O
+the	O
+proteomes	O
+of	O
+the	O
+oomycetes	O
+(	O
+64	O
+proteins	O
+in	O
+Phytophthora	B
+ramorum	I
+and	O
+75	O
+in	O
+Phytophthora	B
+sojae	I
+)	O
+.	O
+
+Proteins	O
+containing	O
+the	O
+Chitin	O
+recognition	O
+protein	O
+domain	O
+(	O
+PF00187	O
+)	O
+are	O
+also	O
+very	O
+common	O
+in	O
+the	O
+proteomes	O
+of	O
+phytopathogens	O
+(	O
+18	O
+in	O
+M	B
+.	I
+grisea	I
+and	O
+16	O
+in	O
+S	B
+.	I
+nodorum	I
+)	O
+.	O
+
+A	O
+role	O
+for	O
+chitin	O
+-	O
+binding	O
+proteins	O
+has	O
+been	O
+proposed	O
+in	O
+protecting	O
+the	O
+fungal	O
+cell	O
+wall	O
+from	O
+chitinases	O
+produced	O
+by	O
+host	O
+plants	O
+[	O
+70	O
+]	O
+.	O
+
+There	O
+are	O
+also	O
+two	O
+other	O
+Pfam	O
+motifs	O
+,	O
+which	O
+are	O
+more	O
+common	O
+in	O
+the	O
+proteomes	O
+of	O
+phytopathogens	O
+,	O
+that	O
+are	O
+found	O
+in	O
+enzymes	O
+involved	O
+in	O
+the	O
+catabolism	O
+of	O
+toxic	O
+compounds	O
+,	O
+namely	O
+arylesterase	O
+(	O
+PF01731	O
+)	O
+and	O
+EthD	O
+protein	O
+(	O
+PF07110	O
+)	O
+which	O
+breakdown	O
+organophosphorus	O
+esters	O
+[	O
+71	O
+]	O
+and	O
+ethyl	O
+tert	O
+-	O
+butyl	O
+ether	O
+[	O
+72	O
+]	O
+,	O
+respectively	O
+.	O
+
+Comparative	O
+secretome	O
+analysis	O
+of	O
+phytopathogenic	O
+and	O
+saprotrophic	O
+filamentous	O
+ascomycetes	O
+
+Studies	O
+in	O
+bacterial	O
+pathogens	O
+and	O
+oomycetes	O
+have	O
+shown	O
+that	O
+a	O
+range	O
+of	O
+secreted	O
+proteins	O
+known	O
+as	O
+effectors	O
+are	O
+important	O
+for	O
+establishing	O
+infection	O
+of	O
+the	O
+host	O
+plant	O
+[	O
+73	O
+]	O
+,	O
+[	O
+74	O
+]	O
+.	O
+
+These	O
+secreted	O
+proteins	O
+may	O
+disable	O
+plant	O
+defences	O
+and	O
+subvert	O
+cellular	O
+processes	O
+to	O
+suit	O
+the	O
+needs	O
+of	O
+invading	O
+pathogens	O
+.	O
+
+Therefore	O
+,	O
+we	O
+decided	O
+also	O
+to	O
+compare	O
+gene	O
+family	O
+size	O
+in	O
+the	O
+secretomes	O
+of	O
+phytopathogens	O
+and	O
+non	O
+-	O
+pathogens	O
+.	O
+
+There	O
+are	O
+a	O
+number	O
+of	O
+programs	O
+available	O
+that	O
+predict	O
+whether	O
+a	O
+protein	O
+is	O
+likely	O
+to	O
+be	O
+secreted	O
+,	O
+although	O
+the	O
+predictions	O
+they	O
+give	O
+significantly	O
+differ	O
+from	O
+each	O
+other	O
+.	O
+
+Therefore	O
+we	O
+defined	O
+the	O
+secretome	O
+of	O
+each	O
+fungal	O
+species	O
+based	O
+on	O
+those	O
+proteins	O
+that	O
+are	O
+predicted	O
+to	O
+be	O
+secreted	O
+by	O
+two	O
+different	O
+programs	O
+:	O
+SignalP	O
+3	O
+.	O
+0	O
+[	O
+75	O
+]	O
+and	O
+WoLFPSORT	O
+[	O
+76	O
+]	O
+.	O
+
+The	O
+size	O
+of	O
+each	O
+secretome	O
+is	O
+summarised	O
+in	O
+Figure	O
+2	O
+.	O
+
+Even	O
+when	O
+using	O
+two	O
+programs	O
+,	O
+the	O
+sizes	O
+of	O
+predicted	O
+secretomes	O
+can	O
+vary	O
+greatly	O
+.	O
+
+For	O
+example	O
+,	O
+a	O
+similar	O
+analysis	O
+for	O
+M	B
+.	I
+grisea	I
+using	O
+SignalP	O
+and	O
+ProtComp	O
+(	O
+www	O
+.	O
+Softberry	O
+.	O
+com	O
+)	O
+predicted	O
+only	O
+739	O
+secreted	O
+proteins	O
+(	O
+out	O
+of	O
+a	O
+proteome	O
+of	O
+11	O
+,	O
+109	O
+)	O
+compared	O
+to	O
+our	O
+prediction	O
+of	O
+1	O
+,	O
+546	O
+secreted	O
+proteins	O
+(	O
+out	O
+of	O
+a	O
+proteome	O
+of	O
+12	O
+,	O
+841	O
+)	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+size	O
+of	O
+the	O
+secretomes	O
+for	O
+each	O
+species	O
+varied	O
+from	O
+5	O
+%	O
+-	O
+12	O
+%	O
+of	O
+the	O
+total	O
+proteome	O
+.	O
+
+Overall	O
+,	O
+the	O
+size	O
+of	O
+the	O
+secretomes	O
+from	O
+phytopathogens	O
+did	O
+not	O
+differ	O
+greatly	O
+from	O
+that	O
+of	O
+non	O
+-	O
+pathogens	O
+.	O
+
+Table	O
+8	O
+shows	O
+a	O
+list	O
+of	O
+Pfam	O
+motifs	O
+,	O
+not	O
+found	O
+in	O
+the	O
+secretomes	O
+of	O
+non	O
+-	O
+pathogenic	O
+filamentous	O
+ascomycetes	O
+,	O
+that	O
+were	O
+present	O
+in	O
+at	O
+least	O
+three	O
+phytopathogenic	O
+fungal	O
+species	O
+.	O
+
+The	O
+Isochorismatase	O
+motif	O
+(	O
+PF00857	O
+)	O
+was	O
+found	O
+in	O
+the	O
+secretomes	O
+of	O
+all	O
+five	O
+species	O
+of	O
+phytopathogen	O
+.	O
+
+Isochorismatase	O
+catalyses	O
+the	O
+conversion	O
+of	O
+isochorismate	O
+to	O
+2	O
+,	O
+3	O
+-	O
+dihydroxybenzoate	O
+and	O
+pyruvate	O
+.	O
+
+It	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+synthesis	O
+of	O
+the	O
+anti	O
+-	O
+microbial	O
+compound	O
+phenazine	O
+by	O
+Pseudomonas	B
+aeruginosa	I
+[	O
+77	O
+]	O
+and	O
+the	O
+siderophore	O
+,	O
+enterobactin	O
+,	O
+by	O
+Escherichia	B
+coli	I
+[	O
+78	O
+]	O
+.	O
+
+The	O
+isochorismatase	O
+motif	O
+is	O
+also	O
+found	O
+in	O
+a	O
+number	O
+of	O
+hydrolases	O
+,	O
+such	O
+as	O
+nicotinamidase	O
+that	O
+converts	O
+nicotinamide	O
+to	O
+nicotinic	O
+acid	O
+[	O
+79	O
+]	O
+.	O
+
+Members	O
+of	O
+this	O
+family	O
+are	O
+found	O
+in	O
+all	O
+filamentous	O
+ascomycetes	O
+,	O
+but	O
+interestingly	O
+they	O
+are	O
+only	O
+secreted	O
+in	O
+phytopathogens	O
+.	O
+
+Salicylic	O
+acid	O
+is	O
+synthesised	O
+in	O
+plants	O
+in	O
+response	O
+to	O
+pathogen	O
+attack	O
+and	O
+mediates	O
+plant	O
+defences	O
+.	O
+
+As	O
+isochorismate	O
+is	O
+a	O
+precursor	O
+of	O
+salicyclic	O
+acid	O
+[	O
+80	O
+]	O
+,	O
+it	O
+may	O
+be	O
+worth	O
+speculating	O
+that	O
+isochorismatases	O
+secreted	O
+by	O
+fungi	O
+could	O
+act	O
+to	O
+reduce	O
+salicylic	O
+acid	O
+accumulation	O
+in	O
+response	O
+to	O
+pathogen	O
+attack	O
+and	O
+thus	O
+inhibit	O
+plant	O
+defence	O
+responses	O
+.	O
+
+The	O
+secreted	O
+isochorismatases	O
+(	O
+apart	O
+from	O
+one	O
+of	O
+the	O
+proteins	O
+from	O
+S	B
+.	I
+nodorum	I
+)	O
+all	O
+show	O
+sequence	O
+similarity	O
+to	O
+ycaC	O
+from	O
+E	B
+.	I
+coli	I
+,	O
+an	O
+octameric	O
+hydrolase	O
+of	O
+unknown	O
+function	O
+[	O
+81	O
+]	O
+.	O
+
+Pfam	O
+motifs	O
+found	O
+in	O
+the	O
+secretomes	O
+of	O
+at	O
+least	O
+three	O
+species	O
+of	O
+phytopathogens	O
+,	O
+but	O
+not	O
+in	O
+any	O
+of	O
+the	O
+non	O
+-	O
+pathogens	O
+also	O
+include	O
+those	O
+found	O
+in	O
+enzymes	O
+potentially	O
+involved	O
+in	O
+detoxification	O
+,	O
+such	O
+as	O
+arylesterase	O
+and	O
+amidohydrolase	O
+,	O
+and	O
+also	O
+beta	O
+-	O
+ketoacyl	O
+synthase	O
+,	O
+which	O
+catalyses	O
+the	O
+condensation	O
+of	O
+malonyl	O
+-	O
+ACP	O
+with	O
+a	O
+growing	O
+fatty	O
+acid	O
+chain	O
+and	O
+is	O
+found	O
+as	O
+a	O
+component	O
+of	O
+a	O
+number	O
+of	O
+enzyme	O
+systems	O
+,	O
+including	O
+fatty	O
+acid	O
+synthases	O
+and	O
+polyketide	O
+synthases	O
+[	O
+82	O
+]	O
+,	O
+[	O
+83	O
+]	O
+.	O
+
+Table	O
+9	O
+shows	O
+a	O
+list	O
+of	O
+Pfam	O
+motifs	O
+that	O
+are	O
+more	O
+common	O
+in	O
+the	O
+secretomes	O
+of	O
+phytopathogens	O
+as	O
+compared	O
+to	O
+saprotrophs	O
+.	O
+
+These	O
+include	O
+a	O
+number	O
+of	O
+secreted	O
+proteases	O
+,	O
+transcription	O
+factors	O
+and	O
+components	O
+of	O
+signal	O
+transduction	O
+pathways	O
+.	O
+
+The	O
+Kelch	O
+domain	O
+(	O
+PF01344	O
+)	O
+shows	O
+the	O
+most	O
+striking	O
+difference	O
+in	O
+distribution	O
+between	O
+phytopathogenic	O
+and	O
+non	O
+-	O
+pathogenic	O
+genomes	O
+.	O
+
+This	O
+50	O
+-	O
+residue	O
+domain	O
+is	O
+found	O
+in	O
+a	O
+number	O
+of	O
+actin	O
+-	O
+binding	O
+proteins	O
+[	O
+84	O
+]	O
+,	O
+as	O
+well	O
+as	O
+enzymes	O
+such	O
+as	O
+galactose	O
+oxidase	O
+and	O
+neuraminidase	O
+.	O
+
+The	O
+putative	O
+function	O
+of	O
+each	O
+secreted	O
+Kelch	O
+domain	O
+-	O
+containing	O
+protein	O
+was	O
+ascertained	O
+by	O
+performing	O
+a	O
+BLAST	O
+search	O
+against	O
+the	O
+NCBI	O
+non	O
+-	O
+redundant	O
+protein	O
+database	O
+(	O
+Table	O
+10	O
+)	O
+.	O
+
+A	O
+number	O
+of	O
+these	O
+seem	O
+to	O
+be	O
+galactose	O
+oxidases	O
+,	O
+enzymes	O
+which	O
+catalyse	O
+the	O
+oxidation	O
+of	O
+a	O
+range	O
+of	O
+primary	O
+alcohols	O
+,	O
+including	O
+galactose	O
+,	O
+to	O
+the	O
+corresponding	O
+aldehyde	O
+with	O
+the	O
+concomitant	O
+reduction	O
+of	O
+oxygen	O
+to	O
+hydrogen	O
+peroxide	O
+(	O
+H2O2	O
+)	O
+[	O
+85	O
+]	O
+.	O
+
+Galactose	O
+oxidase	O
+shares	O
+a	O
+copper	O
+radical	O
+oxidase	O
+motif	O
+with	O
+the	O
+hydrogen	O
+peroxide	O
+-	O
+generating	O
+glyoxal	O
+oxidases	O
+involved	O
+in	O
+lignin	O
+-	O
+degradation	O
+in	O
+Phanerochaete	B
+chrysosporium	I
+[	O
+86	O
+]	O
+.	O
+
+H2O2	O
+-	O
+producing	O
+copper	O
+oxidases	O
+have	O
+been	O
+shown	O
+to	O
+have	O
+roles	O
+in	O
+morphogenesis	O
+,	O
+in	O
+the	O
+corn	B
+-	O
+smut	O
+fungus	O
+Ustilago	B
+maydis	I
+for	O
+example	O
+,	O
+a	O
+glyoxal	O
+oxidase	O
+is	O
+required	O
+for	O
+filamentous	O
+growth	O
+and	O
+pathogenicity	O
+[	O
+87	O
+]	O
+and	O
+a	O
+galactose	O
+oxidase	O
+is	O
+involved	O
+in	O
+fruiting	O
+body	O
+formation	O
+in	O
+the	O
+gram	O
+-	O
+negative	O
+bacterium	O
+Stigmatella	B
+aurantiaca	I
+[	O
+88	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+list	O
+of	O
+Pfam	O
+motifs	O
+more	O
+common	O
+in	O
+the	O
+secretomes	O
+of	O
+phytopathogens	O
+also	O
+includes	O
+those	O
+found	O
+in	O
+copper	O
+amine	O
+oxidases	O
+,	O
+H2O2	O
+-	O
+generating	O
+enzymes	O
+that	O
+catalyse	O
+the	O
+oxidative	O
+deamination	O
+of	O
+primary	O
+amines	O
+to	O
+the	O
+corresponding	O
+aldehydes	O
+[	O
+89	O
+]	O
+and	O
+peroxidases	O
+,	O
+haem	O
+-	O
+containing	O
+enzymes	O
+that	O
+use	O
+hydrogen	O
+peroxide	O
+as	O
+the	O
+electron	O
+acceptor	O
+to	O
+catalyse	O
+a	O
+number	O
+of	O
+oxidative	O
+reactions	O
+.	O
+
+Secreted	O
+fungal	O
+peroxidases	O
+include	O
+enzymes	O
+involved	O
+in	O
+lignin	O
+breakdown	O
+by	O
+the	O
+white	O
+rot	O
+fungus	O
+Phanerochaete	B
+chrysosporium	I
+[	O
+90	O
+]	O
+,	O
+but	O
+in	O
+plants	O
+they	O
+generate	O
+reactive	O
+oxygen	O
+species	O
+and	O
+are	O
+involved	O
+in	O
+defence	O
+responses	O
+and	O
+growth	O
+induction	O
+[	O
+91	O
+]	O
+.	O
+
+A	O
+number	O
+of	O
+other	O
+secreted	O
+Kelch	O
+domain	O
+-	O
+containing	O
+proteins	O
+have	O
+similarity	O
+to	O
+proteins	O
+of	O
+unknown	O
+function	O
+from	O
+species	O
+of	O
+the	O
+bacterial	O
+phytopathogen	O
+Xanthomonas	O
+.	O
+
+Many	O
+Kelch	O
+domain	O
+-	O
+containing	O
+proteins	O
+are	O
+involved	O
+in	O
+cytoskeletal	O
+rearrangement	O
+and	O
+cell	O
+morphology	O
+[	O
+92	O
+]	O
+,	O
+[	O
+93	O
+]	O
+.	O
+
+It	O
+may	O
+be	O
+worth	O
+speculating	O
+that	O
+secreted	O
+Kelch	O
+domain	O
+-	O
+containing	O
+proteins	O
+could	O
+act	O
+as	O
+effectors	O
+,	O
+causing	O
+changes	O
+in	O
+the	O
+arrangement	O
+of	O
+the	O
+cytoskeleton	O
+of	O
+infected	O
+plants	O
+to	O
+aid	O
+the	O
+proliferation	O
+of	O
+fungal	O
+hyphae	O
+.	O
+
+It	O
+has	O
+recently	O
+been	O
+shown	O
+,	O
+for	O
+example	O
+,	O
+that	O
+M	B
+.	I
+grisea	I
+co	O
+-	O
+opts	O
+plasmodesmata	O
+to	O
+move	O
+from	O
+cell	O
+to	O
+cell	O
+in	O
+infected	O
+rice	B
+leaves	O
+[	O
+94	O
+]	O
+and	O
+would	O
+therefore	O
+need	O
+to	O
+peturb	O
+cytoskeletal	O
+organisation	O
+in	O
+rice	B
+epidermal	O
+cells	O
+.	O
+
+There	O
+are	O
+other	O
+Pfam	O
+domains	O
+that	O
+are	O
+more	O
+common	O
+in	O
+the	O
+secretomes	O
+of	O
+phytopathogens	O
+that	O
+may	O
+potentially	O
+be	O
+found	O
+in	O
+effectors	O
+such	O
+as	O
+the	O
+PAN	O
+domain	O
+(	O
+PF00024	O
+)	O
+,	O
+that	O
+mediates	O
+protein	O
+-	O
+protein	O
+and	O
+protein	O
+-	O
+carbohydrate	O
+interactions	O
+[	O
+95	O
+]	O
+and	O
+the	O
+F5	O
+/	O
+8	O
+type	O
+C	O
+domain	O
+(	O
+PF00754	O
+)	O
+,	O
+found	O
+in	O
+the	O
+discoidin	O
+family	O
+of	O
+proteins	O
+involved	O
+in	O
+cell	O
+-	O
+adhesion	O
+or	O
+developmental	O
+processes	O
+[	O
+96	O
+]	O
+.	O
+
+Discussion	O
+
+One	O
+of	O
+the	O
+most	O
+fundamental	O
+aims	O
+in	O
+plant	O
+pathology	O
+research	O
+is	O
+to	O
+define	O
+precisely	O
+the	O
+difference	O
+between	O
+pathogenic	O
+and	O
+non	O
+-	O
+pathogenic	O
+microorganisms	O
+.	O
+
+The	O
+answer	O
+cannot	O
+be	O
+one	O
+of	O
+simple	O
+phylogeny	O
+,	O
+because	O
+phytopathogenic	O
+species	O
+are	O
+found	O
+in	O
+all	O
+taxonomic	O
+divisions	O
+of	O
+fungi	O
+and	O
+are	O
+often	O
+closely	O
+related	O
+to	O
+non	O
+-	O
+pathogenic	O
+species	O
+[	O
+3	O
+]	O
+.	O
+
+Before	O
+the	O
+availability	O
+of	O
+genomic	O
+sequences	O
+and	O
+high	O
+throughput	O
+approaches	O
+to	O
+study	O
+gene	O
+function	O
+[	O
+20	O
+]	O
+,	O
+research	O
+was	O
+concentrated	O
+on	O
+the	O
+search	O
+for	O
+single	O
+pathogenicity	O
+factors	O
+;	O
+genes	O
+that	O
+are	O
+dispensable	O
+for	O
+saprophytic	O
+growth	O
+but	O
+essential	O
+for	O
+successful	O
+infection	O
+of	O
+the	O
+host	O
+plant	O
+[	O
+4	O
+]	O
+,	O
+[	O
+97	O
+]	O
+.	O
+
+However	O
+,	O
+rather	O
+than	O
+encoding	O
+novel	O
+proteins	O
+found	O
+only	O
+in	O
+phytopathogens	O
+,	O
+the	O
+majority	O
+of	O
+pathogenicity	O
+factors	O
+discovered	O
+in	O
+this	O
+way	O
+have	O
+been	O
+found	O
+to	O
+be	O
+involved	O
+in	O
+signalling	O
+cascades	O
+and	O
+metabolic	O
+pathways	O
+and	O
+hence	O
+are	O
+conserved	O
+in	O
+most	O
+species	O
+of	O
+fungi	O
+[	O
+5	O
+]	O
+.	O
+
+Components	O
+of	O
+signalling	O
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+that	O
+in	O
+the	O
+budding	O
+yeast	B
+S	B
+.	I
+cerevisiae	I
+are	O
+responsible	O
+for	O
+responses	O
+to	O
+pheromones	O
+,	O
+nutritional	O
+starvation	O
+and	O
+osmotic	O
+stress	O
+[	O
+9	O
+]	O
+have	O
+in	O
+many	O
+cases	O
+evolved	O
+different	O
+roles	O
+in	O
+the	O
+life	O
+cycle	O
+of	O
+pathogens	O
+,	O
+such	O
+as	O
+controlling	O
+appressorium	O
+formation	O
+,	O
+dimorphism	O
+and	O
+growth	O
+[	O
+10	O
+]	O
+.	O
+
+Although	O
+the	O
+central	O
+components	O
+of	O
+signalling	O
+are	O
+conserved	O
+between	O
+phytopathogens	O
+and	O
+S	B
+.	I
+cerevisiae	I
+,	O
+the	O
+receptors	O
+are	O
+often	O
+different	O
+,	O
+reflecting	O
+the	O
+different	O
+environmental	O
+cues	O
+to	O
+which	O
+the	O
+pathogen	O
+needs	O
+to	O
+respond	O
+[	O
+11	O
+]	O
+,	O
+[	O
+98	O
+]	O
+.	O
+
+Analysis	O
+of	O
+all	O
+available	O
+genome	O
+sequences	O
+from	O
+a	O
+wider	O
+range	O
+of	O
+fungal	O
+species	O
+has	O
+for	O
+the	O
+first	O
+time	O
+allowed	O
+us	O
+to	O
+address	O
+the	O
+differences	O
+between	O
+phytopathogens	O
+and	O
+non	O
+-	O
+pathogens	O
+at	O
+a	O
+whole	O
+genome	O
+level	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+the	O
+e	O
+-	O
+Fungi	O
+data	O
+warehouse	O
+provides	O
+a	O
+means	O
+to	O
+interrogate	O
+the	O
+vast	O
+amounts	O
+of	O
+genomic	O
+and	O
+functional	O
+data	O
+available	O
+in	O
+a	O
+simple	O
+integrated	O
+manner	O
+[	O
+26	O
+]	O
+.	O
+
+Previous	O
+research	O
+,	O
+in	O
+which	O
+EST	O
+datasets	O
+were	O
+compared	O
+with	O
+genomic	O
+sequences	O
+,	O
+suggested	O
+that	O
+the	O
+expressed	O
+gene	O
+inventories	O
+of	O
+phytopathogenic	O
+species	O
+were	O
+not	O
+significantly	O
+more	O
+similar	O
+to	O
+one	O
+another	O
+than	O
+to	O
+those	O
+of	O
+saprotrophic	O
+filamentous	O
+fungi	O
+[	O
+99	O
+]	O
+.	O
+
+We	O
+clustered	O
+sets	O
+of	O
+predicted	O
+proteins	O
+from	O
+36	O
+different	O
+species	O
+of	O
+fungi	O
+and	O
+oomycetes	O
+into	O
+groups	O
+of	O
+potential	O
+orthologues	O
+and	O
+the	O
+species	O
+distribution	O
+of	O
+members	O
+of	O
+each	O
+cluster	O
+was	O
+ascertained	O
+.	O
+
+There	O
+were	O
+no	O
+clusters	O
+that	O
+were	O
+completely	O
+specific	O
+to	O
+phytopathogenic	O
+species	O
+across	O
+both	O
+fungi	O
+and	O
+oomycetes	O
+,	O
+suggesting	O
+that	O
+the	O
+presence	O
+of	O
+novel	O
+,	O
+universal	O
+pathogenicity	O
+factors	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogens	O
+is	O
+unlikely	O
+.	O
+
+This	O
+was	O
+confirmed	O
+by	O
+looking	O
+at	O
+clusters	O
+containing	O
+empirically	O
+defined	O
+pathogenicity	O
+factors	O
+,	O
+where	O
+homologues	O
+of	O
+many	O
+of	O
+these	O
+were	O
+found	O
+in	O
+all	O
+species	O
+studied	O
+and	O
+none	O
+were	O
+conserved	O
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+the	O
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+only	O
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+phytopathogens	O
+.	O
+
+A	O
+small	O
+number	O
+were	O
+only	O
+found	O
+in	O
+a	O
+single	O
+species	O
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+fungus	O
+and	O
+probably	O
+represented	O
+proteins	O
+that	O
+are	O
+highly	O
+specialised	O
+for	O
+a	O
+particular	O
+role	O
+in	O
+a	O
+specific	O
+pathogenic	O
+species	O
+,	O
+for	O
+example	O
+in	O
+host	O
+-	O
+plant	O
+recognition	O
+[	O
+54	O
+]	O
+.	O
+
+Previous	O
+research	O
+also	O
+suggested	O
+that	O
+the	O
+gene	O
+inventories	O
+of	O
+filamentous	O
+fungi	O
+were	O
+more	O
+similar	O
+to	O
+each	O
+other	O
+than	O
+to	O
+those	O
+of	O
+unicellular	O
+yeasts	O
+[	O
+99	O
+]	O
+.	O
+
+Analysis	O
+of	O
+the	O
+clusters	O
+of	O
+similar	O
+proteins	O
+show	O
+some	O
+clusters	O
+that	O
+are	O
+found	O
+in	O
+all	O
+species	O
+of	O
+filamentous	O
+fungi	O
+(	O
+including	O
+ascomycetes	O
+,	O
+basidiomycetes	O
+and	O
+zygomycetes	O
+)	O
+but	O
+are	O
+not	O
+present	O
+in	O
+the	O
+genomes	O
+of	O
+yeasts	O
+,	O
+consistent	O
+with	O
+the	O
+original	O
+conclusion	O
+.	O
+
+These	O
+contain	O
+a	O
+number	O
+of	O
+proteins	O
+that	O
+are	O
+likely	O
+to	O
+be	O
+involved	O
+in	O
+morphological	O
+changes	O
+associated	O
+with	O
+the	O
+more	O
+complex	O
+filamentous	O
+lifestyle	O
+,	O
+as	O
+well	O
+those	O
+involved	O
+in	O
+secondary	O
+metabolism	O
+and	O
+signalling	O
+cascades	O
+that	O
+are	O
+not	O
+found	O
+in	O
+yeasts	O
+.	O
+
+In	O
+particular	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+filamentous	O
+fungi	O
+use	O
+a	O
+wider	O
+variety	O
+of	O
+lipid	O
+molecules	O
+for	O
+the	O
+purpose	O
+of	O
+signalling	O
+.	O
+
+Some	O
+of	O
+these	O
+may	O
+act	O
+as	O
+pheromones	O
+,	O
+or	O
+hormones	O
+-	O
+chemical	O
+messengers	O
+diffusing	O
+from	O
+one	O
+cell	O
+to	O
+another	O
+to	O
+elicit	O
+a	O
+physiological	O
+or	O
+developmental	O
+response	O
+[	O
+37	O
+]	O
+.	O
+
+A	O
+number	O
+of	O
+these	O
+innovations	O
+to	O
+the	O
+filamentous	O
+lifestyle	O
+may	O
+serve	O
+important	O
+roles	O
+in	O
+pathogenesis	O
+as	O
+well	O
+,	O
+because	O
+homologues	O
+of	O
+a	O
+number	O
+of	O
+pathogenicity	O
+factors	O
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+found	O
+only	O
+in	O
+filamentous	O
+ascomycetes	O
+.	O
+
+The	O
+distribution	O
+of	O
+filamentous	O
+fungi	O
+-	O
+specific	O
+proteins	O
+,	O
+such	O
+as	O
+involved	O
+in	O
+those	O
+cytoskeletal	O
+rearrangements	O
+and	O
+fruiting	O
+body	O
+formation	O
+,	O
+throughout	O
+the	O
+fungal	O
+kingdom	O
+(	O
+and	O
+in	O
+some	O
+cases	O
+in	O
+oomycetes	O
+as	O
+well	O
+)	O
+,	O
+suggests	O
+that	O
+the	O
+last	O
+common	O
+ancestral	O
+fungus	O
+may	O
+well	O
+have	O
+been	O
+multi	O
+-	O
+cellular	O
+and	O
+the	O
+evolution	O
+of	O
+uni	O
+-	O
+cellular	O
+fungi	O
+was	O
+likely	O
+associated	O
+with	O
+massive	O
+gene	O
+loss	O
+.	O
+
+For	O
+example	O
+,	O
+it	O
+has	O
+been	O
+shown	O
+that	O
+early	O
+in	O
+ascomycete	O
+evolution	O
+there	O
+was	O
+a	O
+proliferation	O
+of	O
+subtilase	O
+-	O
+type	O
+protease	O
+-	O
+encoding	O
+genes	O
+that	O
+have	O
+been	O
+retained	O
+in	O
+some	O
+filamentous	O
+ascomycete	O
+lineages	O
+,	O
+but	O
+lost	O
+in	O
+the	O
+yeast	B
+lineage	O
+[	O
+100	O
+]	O
+.	O
+
+It	O
+has	O
+previously	O
+been	O
+speculated	O
+that	O
+the	O
+evolution	O
+of	O
+phytopathogenesis	O
+was	O
+associated	O
+with	O
+the	O
+expansion	O
+of	O
+certain	O
+gene	O
+families	O
+[	O
+1	O
+]	O
+.	O
+
+Duplication	O
+of	O
+an	O
+ancestral	O
+gene	O
+,	O
+followed	O
+by	O
+mutation	O
+allows	O
+members	O
+of	O
+the	O
+family	O
+to	O
+take	O
+on	O
+new	O
+functions	O
+[	O
+101	O
+]	O
+.	O
+
+For	O
+example	O
+,	O
+genomes	O
+of	O
+the	O
+filamentous	O
+ascomycetes	O
+studied	O
+here	O
+have	O
+between	O
+40	O
+and	O
+140	O
+cytochrome	O
+P450	O
+-	O
+encoding	O
+genes	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+that	O
+are	O
+involved	O
+in	O
+toxin	O
+biosynthesis	O
+,	O
+lipid	O
+metabolism	O
+,	O
+alkane	O
+assimilation	O
+and	O
+detoxification	O
+[	O
+102	O
+]	O
+and	O
+which	O
+probably	O
+arose	O
+via	O
+gene	O
+duplication	O
+and	O
+functional	O
+diversification	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+genome	O
+of	O
+the	O
+budding	O
+yeast	B
+S	B
+.	I
+cerevisiae	I
+has	O
+only	O
+three	O
+cytochrome	O
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+-	O
+encoding	O
+enzymes	O
+.	O
+
+We	O
+have	O
+shown	O
+here	O
+that	O
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+to	O
+be	O
+large	O
+differences	O
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+the	O
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+filamentous	O
+fungi	O
+compared	O
+to	O
+unicellular	O
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+.	O
+
+To	O
+study	O
+the	O
+differences	O
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+phytopathogenic	O
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+,	O
+we	O
+concentrated	O
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+where	O
+there	O
+are	O
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+number	O
+of	O
+phytopathogenic	O
+species	O
+genomes	O
+have	O
+been	O
+sequenced	O
+along	O
+with	O
+closely	O
+related	O
+non	O
+-	O
+pathogens	O
+.	O
+
+Protein	O
+families	O
+were	O
+defined	O
+using	O
+Pfam	O
+motifs	O
+[	O
+57	O
+]	O
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+the	O
+predicted	O
+protein	O
+sets	O
+for	O
+each	O
+species	O
+analysed	O
+in	O
+order	O
+to	O
+identify	O
+domains	O
+that	O
+were	O
+specific	O
+to	O
+or	O
+more	O
+common	O
+in	O
+the	O
+genomes	O
+of	O
+phytopathogens	O
+.	O
+
+Not	O
+surprisingly	O
+,	O
+many	O
+of	O
+the	O
+protein	O
+families	O
+we	O
+identified	O
+are	O
+likely	O
+to	O
+be	O
+associated	O
+with	O
+pathogenic	O
+processes	O
+such	O
+as	O
+plant	O
+cell	O
+wall	O
+degradation	O
+,	O
+toxin	O
+biosynthesis	O
+,	O
+formation	O
+of	O
+reactive	O
+oxygen	O
+species	O
+and	O
+detoxification	O
+[	O
+5	O
+]	O
+.	O
+
+Studies	O
+of	O
+bacterial	O
+phytopathogens	O
+have	O
+shown	O
+the	O
+importance	O
+of	O
+effectors	O
+,	O
+secreted	O
+proteins	O
+that	O
+disable	O
+plant	O
+defences	O
+and	O
+subvert	O
+metabolic	O
+and	O
+morphological	O
+processes	O
+for	O
+the	O
+benefit	O
+of	O
+the	O
+invading	O
+pathogen	O
+and	O
+which	O
+require	O
+delivery	O
+via	O
+a	O
+type	O
+III	O
+secretion	O
+system	O
+that	O
+are	O
+often	O
+deployed	O
+during	O
+pathogenesis	O
+[	O
+73	O
+]	O
+.	O
+
+Bacterial	O
+type	O
+III	O
+secreted	O
+effectors	O
+(	O
+T3SEs	O
+)	O
+have	O
+been	O
+shown	O
+to	O
+target	O
+salicyclic	O
+acid	O
+and	O
+abscisic	O
+acid	O
+-	O
+dependent	O
+defences	O
+,	O
+host	O
+vesicle	O
+trafficking	O
+,	O
+transcription	O
+and	O
+RNA	O
+metabolism	O
+,	O
+and	O
+several	O
+components	O
+of	O
+the	O
+plant	O
+defence	O
+signalling	O
+networks	O
+[	O
+103	O
+]	O
+.	O
+
+Very	O
+recently	O
+,	O
+potential	O
+effector	O
+-	O
+encoding	O
+genes	O
+have	O
+been	O
+identified	O
+in	O
+the	O
+genomes	O
+of	O
+several	O
+species	O
+of	O
+oomycete	O
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+are	O
+defined	O
+by	O
+the	O
+presence	O
+of	O
+a	O
+conserved	O
+RXLR	O
+-	O
+EER	O
+motif	O
+downstream	O
+of	O
+the	O
+signal	O
+peptide	O
+sequence	O
+[	O
+74	O
+]	O
+.	O
+
+The	O
+RXLR	O
+-	O
+EER	O
+motif	O
+is	O
+necessary	O
+for	O
+delivery	O
+of	O
+effector	O
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+into	O
+host	O
+plant	O
+cells	O
+and	O
+is	O
+therefore	O
+critical	O
+to	O
+their	O
+biological	O
+activity	O
+[	O
+74	O
+]	O
+.	O
+
+To	O
+identify	O
+potential	O
+fungal	O
+effectors	O
+,	O
+we	O
+compared	O
+Pfam	O
+motif	O
+frequency	O
+between	O
+the	O
+secretomes	O
+of	O
+phytopathogens	O
+and	O
+non	O
+-	O
+pathogens	O
+.	O
+
+This	O
+analysis	O
+identified	O
+potential	O
+effector	O
+-	O
+encoding	O
+genes	O
+,	O
+including	O
+secreted	O
+proteases	O
+,	O
+transcription	O
+factors	O
+and	O
+proteins	O
+that	O
+may	O
+be	O
+involved	O
+in	O
+cytoskeletal	O
+rearrangements	O
+(	O
+such	O
+as	O
+Kelch	O
+-	O
+domain	O
+containing	O
+proteins	O
+)	O
+and	O
+protein	O
+-	O
+protein	O
+interactions	O
+,	O
+as	O
+well	O
+as	O
+a	O
+group	O
+of	O
+pathogen	O
+-	O
+specific	O
+secreted	O
+isochorisimatases	O
+that	O
+potentially	O
+could	O
+suppress	O
+salicyclic	O
+acid	O
+-	O
+dependent	O
+host	O
+plant	O
+defences	O
+.	O
+
+Bacterial	O
+T3SEs	O
+are	O
+injected	O
+directly	O
+into	O
+the	O
+host	O
+cytoplasm	O
+via	O
+the	O
+type	O
+III	O
+secretion	O
+injection	O
+apparatus	O
+[	O
+73	O
+]	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+potential	O
+fungal	O
+effectors	O
+identified	O
+in	O
+this	O
+study	O
+appear	O
+to	O
+be	O
+secreted	O
+by	O
+the	O
+normal	O
+cellular	O
+secretory	O
+pathway	O
+via	O
+the	O
+endoplasmic	O
+reticulum	O
+and	O
+the	O
+mechanism	O
+by	O
+which	O
+fungal	O
+effectors	O
+might	O
+be	O
+taken	O
+up	O
+by	O
+plant	O
+cells	O
+and	O
+enter	O
+into	O
+the	O
+host	O
+cytoplasm	O
+is	O
+currently	O
+unknown	O
+.	O
+
+Although	O
+the	O
+evolution	O
+of	O
+phytopathogenicity	O
+is	O
+likely	O
+to	O
+have	O
+happened	O
+several	O
+times	O
+and	O
+the	O
+lifestyles	O
+of	O
+these	O
+fungi	O
+are	O
+diverse	O
+,	O
+a	O
+comparison	O
+of	O
+gene	O
+inventories	O
+of	O
+a	O
+number	O
+of	O
+species	O
+using	O
+a	O
+powerful	O
+resource	O
+,	O
+such	O
+as	O
+e	O
+-	O
+Fungi	O
+,	O
+has	O
+allowed	O
+us	O
+to	O
+pinpoint	O
+new	O
+gene	O
+families	O
+that	O
+may	O
+serve	O
+important	O
+roles	O
+in	O
+the	O
+virulence	O
+of	O
+phytopathogens	O
+,	O
+allowing	O
+their	O
+selection	O
+for	O
+gene	O
+functional	O
+studies	O
+,	O
+that	O
+are	O
+currently	O
+in	O
+progress	O
+.	O
+
+The	O
+analyses	O
+deployed	O
+here	O
+may	O
+also	O
+offer	O
+a	O
+blueprint	O
+for	O
+the	O
+types	O
+of	O
+larger	O
+,	O
+more	O
+comprehensive	O
+studies	O
+that	O
+will	O
+be	O
+necessary	O
+to	O
+interpret	O
+the	O
+large	O
+flow	O
+of	O
+genetic	O
+data	O
+that	O
+will	O
+result	O
+from	O
+next	O
+generation	O
+DNA	O
+sequence	O
+analysis	O
+utilizing	O
+both	O
+a	O
+much	O
+wider	O
+variety	O
+of	O
+fungal	O
+pathogen	O
+species	O
+and	O
+also	O
+large	O
+sets	O
+of	O
+individual	O
+isolates	O
+of	O
+existing	O
+species	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Clustering	O
+of	O
+sequences	O
+
+Sets	O
+of	O
+predicted	O
+proteins	O
+were	O
+downloaded	O
+for	O
+each	O
+of	O
+the	O
+36	O
+genomes	O
+from	O
+respective	O
+sequencing	O
+project	O
+websites	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Proteins	O
+less	O
+than	O
+40	O
+amino	O
+acids	O
+in	O
+length	O
+were	O
+not	O
+included	O
+in	O
+this	O
+analysis	O
+.	O
+
+Proteins	O
+were	O
+clustered	O
+using	O
+"	O
+all	O
+against	O
+all	O
+"	O
+BLASTP	O
+[	O
+104	O
+]	O
+followed	O
+by	O
+Markov	O
+Chain	O
+Clustering	O
+(	O
+MCL	O
+)	O
+[	O
+27	O
+]	O
+with	O
+2	O
+.	O
+5	O
+as	O
+a	O
+moderate	O
+inflation	O
+value	O
+and	O
+10	O
+-	O
+10	O
+as	O
+an	O
+E	O
+-	O
+value	O
+cut	O
+-	O
+off	O
+,	O
+as	O
+described	O
+previously	O
+[	O
+28	O
+]	O
+,	O
+[	O
+29	O
+]	O
+.	O
+
+Clusters	O
+were	O
+annotated	O
+based	O
+on	O
+best	O
+hit	O
+against	O
+Swiss	O
+-	O
+Prot	O
+protein	O
+database	O
+[	O
+105	O
+]	O
+of	O
+members	O
+of	O
+that	O
+cluster	O
+(	O
+e	O
+-	O
+value	O
+<	O
+10	O
+-	O
+20	O
+using	O
+BLASTP	O
+)	O
+,	O
+or	O
+Pfam	O
+motifs	O
+contained	O
+in	O
+proteins	O
+from	O
+the	O
+cluster	O
+in	O
+the	O
+absence	O
+of	O
+Swiss	O
+-	O
+Prot	O
+hits	O
+.	O
+
+Identification	O
+of	O
+Pfam	O
+motifs	O
+
+The	O
+Pfam	O
+-	O
+A	O
+library	O
+from	O
+release	O
+18	O
+.	O
+0	O
+of	O
+the	O
+Pfam	O
+database	O
+was	O
+downloaded	O
+from	O
+the	O
+Pfam	O
+website	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+sanger	O
+.	O
+ac	O
+.	O
+uk	O
+/	O
+Software	O
+/	O
+Pfam	O
+/	O
+)	O
+.	O
+
+This	O
+library	O
+contains	O
+7973	O
+protein	O
+models	O
+constructed	O
+from	O
+manually	O
+curated	O
+multiple	O
+alignments	O
+and	O
+covers	O
+75	O
+%	O
+of	O
+proteins	O
+in	O
+UniProt	O
+[	O
+44	O
+]	O
+,	O
+[	O
+57	O
+]	O
+.	O
+
+This	O
+library	O
+was	O
+used	O
+to	O
+analyse	O
+the	O
+sequences	O
+of	O
+predicted	O
+proteins	O
+for	O
+all	O
+36	O
+fungal	O
+genomes	O
+to	O
+identify	O
+the	O
+Pfam	O
+motifs	O
+that	O
+each	O
+protein	O
+contains	O
+.	O
+
+The	O
+analysis	O
+was	O
+performed	O
+using	O
+the	O
+"	O
+pfam	O
+_	O
+scan	O
+"	O
+perl	O
+script	O
+(	O
+version	O
+0	O
+.	O
+5	O
+)	O
+downloaded	O
+from	O
+the	O
+Pfam	O
+website	O
+and	O
+HMMER	O
+software	O
+(	O
+downloaded	O
+from	O
+http	O
+:	O
+/	O
+/	O
+hmmer	O
+.	O
+wustl	O
+.	O
+edu	O
+/	O
+)	O
+.	O
+
+Default	O
+thresholds	O
+were	O
+used	O
+,	O
+which	O
+are	O
+hand	O
+-	O
+curated	O
+for	O
+every	O
+family	O
+and	O
+designed	O
+to	O
+minimise	O
+false	O
+positives	O
+[	O
+44	O
+]	O
+.	O
+
+Identification	O
+of	O
+secreted	O
+proteins	O
+
+The	O
+N	O
+-	O
+terminal	O
+sequence	O
+of	O
+each	O
+predicted	O
+protein	O
+from	O
+the	O
+36	O
+fungal	O
+genomes	O
+used	O
+in	O
+this	O
+study	O
+was	O
+analysed	O
+for	O
+the	O
+presence	O
+of	O
+a	O
+signal	O
+peptide	O
+using	O
+SignalP	O
+3	O
+.	O
+0	O
+[	O
+75	O
+]	O
+and	O
+sub	O
+-	O
+cellular	O
+localisation	O
+was	O
+predicted	O
+using	O
+WoLF	O
+PSORT	O
+[	O
+76	O
+]	O
+.	O
+
+Both	O
+these	O
+programs	O
+were	O
+installed	O
+locally	O
+.	O
+
+SignalP	O
+3	O
+.	O
+0	O
+uses	O
+two	O
+different	O
+algorithms	O
+to	O
+identify	O
+signal	O
+sequences	O
+.	O
+
+The	O
+secretome	O
+for	O
+each	O
+fungal	O
+species	O
+was	O
+defined	O
+as	O
+containing	O
+those	O
+proteins	O
+that	O
+were	O
+predicted	O
+have	O
+a	O
+signal	O
+peptide	O
+by	O
+both	O
+prediction	O
+algorithms	O
+from	O
+SignalP	O
+3	O
+.	O
+0	O
+and	O
+also	O
+predicted	O
+to	O
+be	O
+extracellular	O
+by	O
+WoLF	O
+PSORT	O
+.	O
+
+Data	O
+analysis	O
+
+All	O
+the	O
+data	O
+produced	O
+,	O
+as	O
+described	O
+above	O
+,	O
+was	O
+stored	O
+in	O
+the	O
+e	O
+-	O
+Fungi	O
+data	O
+warehouse	O
+[	O
+26	O
+]	O
+from	O
+which	O
+it	O
+can	O
+be	O
+accessed	O
+via	O
+a	O
+web	O
+-	O
+interface	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+e	O
+-	O
+fungi	O
+.	O
+org	O
+.	O
+uk	O
+/	O
+)	O
+.	O
+
+Analyses	O
+described	O
+in	O
+this	O
+study	O
+were	O
+performed	O
+using	O
+the	O
+e	O
+-	O
+Fungi	O
+database	O
+.	O
+
+Supporting	O
+Information	O
+
+Emergence	O
+of	O
+Delayed	O
+Methylmercury	O
+Toxicity	O
+after	O
+Perinatal	O
+Exposure	O
+in	O
+Metallothionein	O
+-	O
+Null	O
+and	O
+Wild	O
+-	O
+Type	O
+C57BL	O
+Mice	B
+
+Abstract	O
+
+Background	O
+
+Although	O
+a	O
+long	O
+latency	O
+period	O
+of	O
+toxicity	O
+after	O
+exposure	O
+to	O
+methylmercury	O
+(	O
+MeHg	O
+)	O
+is	O
+known	O
+to	O
+exist	O
+in	O
+humans	B
+,	O
+few	O
+animal	O
+studies	O
+have	O
+addressed	O
+this	O
+issue	O
+.	O
+
+Substantiation	O
+of	O
+delayed	O
+MeHg	O
+toxicity	O
+in	O
+animals	O
+would	O
+affect	O
+the	O
+risk	O
+evaluation	O
+of	O
+MeHg	O
+.	O
+
+Objectives	O
+
+Our	O
+goal	O
+in	O
+this	O
+study	O
+was	O
+to	O
+demonstrate	O
+the	O
+existence	O
+of	O
+a	O
+latency	O
+period	O
+in	O
+a	O
+rodent	O
+model	O
+in	O
+which	O
+the	O
+toxicity	O
+of	O
+perinatal	O
+MeHg	O
+exposure	O
+becomes	O
+apparent	O
+only	O
+later	O
+in	O
+life	O
+.	O
+
+Our	O
+study	O
+included	O
+metallothionein	O
+(	O
+MT	O
+)	O
+knockout	O
+mice	B
+because	O
+studies	O
+have	O
+suggested	O
+the	O
+potential	O
+susceptibility	O
+of	O
+this	O
+strain	O
+to	O
+the	O
+neurodevelopmental	O
+toxicity	O
+of	O
+MeHg	O
+.	O
+
+Methods	O
+
+Pregnant	O
+MT	O
+-	O
+null	O
+and	O
+wild	O
+-	O
+type	O
+C57Bl	O
+/	O
+6J	O
+mice	B
+were	O
+exposed	O
+to	O
+MeHg	O
+through	O
+their	O
+diet	O
+containing	O
+5	O
+mu	O
+g	O
+Hg	O
+/	O
+g	O
+during	O
+gestation	O
+and	O
+early	O
+lactation	O
+.	O
+
+We	O
+examined	O
+behavioral	O
+functions	O
+of	O
+the	O
+offspring	O
+using	O
+frequently	O
+used	O
+paradigms	O
+,	O
+including	O
+open	O
+field	O
+behavior	O
+(	O
+OPF	O
+)	O
+,	O
+passive	O
+avoidance	O
+(	O
+PA	O
+)	O
+,	O
+and	O
+the	O
+Morris	O
+water	O
+maze	O
+(	O
+MM	O
+)	O
+,	O
+at	O
+ages	O
+of	O
+12	O
+-	O
+13	O
+and	O
+52	O
+-	O
+53	O
+weeks	O
+.	O
+
+Results	O
+
+At	O
+12	O
+weeks	O
+of	O
+age	O
+,	O
+behavioral	O
+effects	O
+of	O
+MeHg	O
+were	O
+not	O
+detected	O
+,	O
+except	O
+for	O
+OPF	O
+performance	O
+in	O
+MeHg	O
+-	O
+exposed	O
+MT	O
+-	O
+null	O
+females	O
+.	O
+
+At	O
+52	O
+weeks	O
+of	O
+age	O
+,	O
+the	O
+MeHg	O
+-	O
+exposed	O
+groups	O
+showed	O
+poorer	O
+performance	O
+both	O
+in	O
+PA	O
+and	O
+MM	O
+,	O
+and	O
+their	O
+OPF	O
+activity	O
+differed	O
+from	O
+controls	O
+.	O
+
+These	O
+effects	O
+of	O
+MeHg	O
+appeared	O
+exaggerated	O
+in	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+.	O
+
+The	O
+brain	O
+Hg	O
+concentration	O
+had	O
+leveled	O
+off	O
+by	O
+13	O
+weeks	O
+of	O
+age	O
+.	O
+
+Conclusions	O
+
+The	O
+results	O
+suggest	O
+the	O
+existence	O
+of	O
+a	O
+long	O
+latency	O
+period	O
+after	O
+perinatal	O
+exposure	O
+to	O
+low	O
+-	O
+level	O
+MeHg	O
+,	O
+in	O
+which	O
+the	O
+behavioral	O
+effects	O
+emerged	O
+long	O
+after	O
+the	O
+leveling	O
+-	O
+off	O
+of	O
+brain	O
+Hg	O
+levels	O
+.	O
+
+Hence	O
+,	O
+the	O
+initial	O
+toxicologic	O
+event	O
+responsible	O
+for	O
+the	O
+late	O
+effects	O
+should	O
+have	O
+occurred	O
+before	O
+this	O
+leveling	O
+-	O
+off	O
+of	O
+brain	O
+Hg	O
+.	O
+
+Methylmercury	O
+(	O
+MeHg	O
+)	O
+poses	O
+serious	O
+and	O
+practical	O
+concerns	O
+for	O
+human	B
+populations	O
+regarding	O
+perinatal	O
+exposure	O
+.	O
+
+Fish	O
+,	O
+especially	O
+large	O
+predator	O
+(	O
+carnivore	O
+)	O
+fish	O
+species	O
+,	O
+accumulate	O
+high	O
+concentrations	O
+of	O
+MeHg	O
+through	O
+the	O
+marine	O
+food	O
+chain	O
+,	O
+and	O
+exposure	O
+of	O
+pregnant	O
+women	B
+to	O
+MeHg	O
+through	O
+the	O
+consumption	O
+of	O
+fish	O
+has	O
+evoked	O
+widespread	O
+concern	O
+due	O
+to	O
+potential	O
+effects	O
+on	O
+offspring	O
+.	O
+
+Two	O
+large	O
+-	O
+scale	O
+cohort	O
+studies	O
+in	O
+fish	O
+-	O
+eating	O
+populations	O
+of	O
+Seychelles	O
+and	O
+Faroe	O
+islanders	O
+are	O
+being	O
+conducted	O
+;	O
+although	O
+the	O
+former	O
+has	O
+not	O
+found	O
+consistent	O
+adverse	O
+developmental	O
+effects	O
+of	O
+MeHg	O
+(	O
+Myers	O
+et	O
+al	O
+.	O
+2007	O
+)	O
+,	O
+the	O
+latter	O
+has	O
+reported	O
+adverse	O
+effects	O
+(	O
+Debes	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Fundamental	O
+reasons	O
+for	O
+this	O
+discrepancy	O
+have	O
+not	O
+been	O
+completely	O
+elucidated	O
+,	O
+and	O
+many	O
+questions	O
+remain	O
+regarding	O
+the	O
+neurotoxicity	O
+of	O
+MeHg	O
+,	O
+despite	O
+extensive	O
+study	O
+.	O
+
+Among	O
+the	O
+unanswered	O
+questions	O
+is	O
+whether	O
+there	O
+is	O
+a	O
+long	O
+latency	O
+period	O
+for	O
+behavioral	O
+manifestations	O
+after	O
+exposure	O
+to	O
+MeHg	O
+(	O
+Clarkson	O
+and	O
+Magos	O
+2006	O
+;	O
+Landrigan	O
+et	O
+al	O
+.	O
+2005	O
+;	O
+Rice	O
+1996	O
+;	O
+Weiss	O
+et	O
+al	O
+.	O
+2005a	O
+,	O
+2005b	O
+)	O
+.	O
+
+Typical	O
+examples	O
+of	O
+latent	O
+toxicity	O
+in	O
+humans	B
+,	O
+including	O
+both	O
+acute	O
+and	O
+chronic	O
+MeHg	O
+exposures	O
+,	O
+have	O
+been	O
+described	O
+in	O
+detail	O
+elsewhere	O
+(	O
+Weiss	O
+et	O
+al	O
+.	O
+2005a	O
+)	O
+.	O
+
+Davidson	O
+et	O
+al	O
+.	O
+
+(	O
+2006	O
+)	O
+recently	O
+suggested	O
+that	O
+effects	O
+of	O
+perinatal	O
+exposure	O
+to	O
+MeHg	O
+may	O
+emerge	O
+9	O
+years	O
+after	O
+birth	O
+in	O
+the	O
+Seychelles	O
+cohort	O
+.	O
+
+Consequently	O
+,	O
+risk	O
+assessments	O
+of	O
+MeHg	O
+exposure	O
+could	O
+be	O
+inaccurate	O
+because	O
+studies	O
+(	O
+human	B
+or	O
+animal	O
+)	O
+usually	O
+do	O
+not	O
+focus	O
+on	O
+later	O
+stages	O
+of	O
+life	O
+and	O
+therefore	O
+could	O
+miss	O
+delayed	O
+effects	O
+.	O
+
+The	O
+possibility	O
+of	O
+delayed	O
+toxicity	O
+is	O
+exemplified	O
+by	O
+the	O
+expanded	O
+Barker	O
+hypothesis	O
+,	O
+which	O
+posits	O
+that	O
+the	O
+origin	O
+of	O
+some	O
+neurodegenerative	O
+diseases	O
+such	O
+as	O
+Parkinson	O
+and	O
+Alzheimer	O
+diseases	O
+lies	O
+in	O
+early	O
+exposure	O
+to	O
+environmental	O
+chemicals	O
+(	O
+Landrigan	O
+et	O
+al	O
+.	O
+2005	O
+)	O
+.	O
+
+Although	O
+epidemiologic	O
+evidence	O
+would	O
+be	O
+ideal	O
+for	O
+exploring	O
+the	O
+possibility	O
+of	O
+delayed	O
+toxicity	O
+(	O
+and	O
+,	O
+indeed	O
+,	O
+data	O
+from	O
+epidemiologic	O
+studies	O
+form	O
+the	O
+basis	O
+of	O
+current	O
+risk	O
+assessment	O
+for	O
+developmental	O
+toxicity	O
+of	O
+MeHg	O
+)	O
+,	O
+considering	O
+the	O
+complex	O
+effects	O
+of	O
+numerous	O
+potential	O
+confounders	O
+and	O
+the	O
+existence	O
+of	O
+multiple	O
+exposures	O
+in	O
+human	B
+populations	O
+,	O
+animal	O
+models	O
+would	O
+likely	O
+make	O
+important	O
+contributions	O
+to	O
+this	O
+field	O
+.	O
+
+Although	O
+numerous	O
+animal	O
+studies	O
+have	O
+described	O
+the	O
+developmental	O
+neurotoxicity	O
+of	O
+MeHg	O
+(	O
+Watanabe	O
+and	O
+Satoh	O
+,	O
+1996	O
+)	O
+,	O
+few	O
+have	O
+addressed	O
+the	O
+latency	O
+issue	O
+.	O
+
+Few	O
+studies	O
+have	O
+evaluated	O
+the	O
+neurobehavioral	O
+effects	O
+in	O
+rodents	O
+longitudinally	O
+beyond	O
+6	O
+months	O
+after	O
+perinatal	O
+exposure	O
+.	O
+
+Spyker	O
+(	O
+1975	O
+)	O
+addressed	O
+this	O
+issue	O
+in	O
+her	O
+pioneering	O
+work	O
+,	O
+reporting	O
+the	O
+late	O
+development	O
+of	O
+behavioral	O
+toxicity	O
+in	O
+mice	B
+prenatally	O
+exposed	O
+to	O
+MeHg	O
+;	O
+it	O
+appeared	O
+,	O
+however	O
+,	O
+that	O
+the	O
+substantial	O
+mortality	O
+and	O
+retarded	O
+growth	O
+among	O
+the	O
+exposed	O
+mice	B
+were	O
+apparent	O
+before	O
+weaning	O
+,	O
+indicating	O
+that	O
+the	O
+doses	O
+used	O
+(	O
+even	O
+though	O
+some	O
+lower	O
+dose	O
+levels	O
+were	O
+included	O
+)	O
+exerted	O
+severe	O
+toxicity	O
+.	O
+
+Using	O
+a	O
+relatively	O
+complex	O
+schedule	O
+-	O
+controlled	O
+operant	O
+behavior	O
+method	O
+,	O
+rats	B
+whose	O
+parents	O
+were	O
+exposed	O
+to	O
+MeHg	O
+(	O
+0	O
+.	O
+5	O
+or	O
+6	O
+.	O
+4	O
+mg	O
+/	O
+L	O
+)	O
+from	O
+4	O
+weeks	O
+before	O
+mating	O
+and	O
+continuing	O
+to	O
+postnatal	O
+day	O
+(	O
+PND	O
+)	O
+16	O
+were	O
+shown	O
+to	O
+be	O
+less	O
+sensitive	O
+to	O
+a	O
+change	O
+in	O
+the	O
+reinforcement	O
+schedule	O
+than	O
+were	O
+their	O
+nonexposed	O
+counterparts	O
+at	O
+28	O
+-	O
+32	O
+months	O
+of	O
+age	O
+(	O
+Newland	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Mice	B
+that	O
+were	O
+perinatally	O
+exposed	O
+to	O
+1	O
+or	O
+3	O
+mg	O
+/	O
+L	O
+MeHg	O
+in	O
+drinking	O
+water	O
+did	O
+not	O
+show	O
+significant	O
+deviation	O
+from	O
+controls	O
+in	O
+behavioral	O
+performance	O
+(	O
+motor	O
+performance	O
+,	O
+memory	O
+,	O
+and	O
+learning	O
+)	O
+at	O
+5	O
+,	O
+15	O
+,	O
+or	O
+26	O
+months	O
+of	O
+age	O
+,	O
+but	O
+the	O
+lifetime	O
+-	O
+exposed	O
+groups	O
+did	O
+show	O
+a	O
+significant	O
+deviation	O
+(	O
+Weiss	O
+et	O
+al	O
+.	O
+2005c	O
+)	O
+.	O
+
+The	O
+existence	O
+of	O
+a	O
+latency	O
+period	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+the	O
+absence	O
+of	O
+effects	O
+earlier	O
+in	O
+life	O
+followed	O
+by	O
+the	O
+emergence	O
+of	O
+effects	O
+at	O
+a	O
+later	O
+stage	O
+of	O
+life	O
+)	O
+has	O
+not	O
+been	O
+demonstrated	O
+in	O
+any	O
+rodent	O
+study	O
+.	O
+
+In	O
+nonhuman	O
+primates	O
+,	O
+delayed	O
+emergence	O
+of	O
+the	O
+signs	O
+of	O
+neurotoxicity	O
+was	O
+observed	O
+several	O
+years	O
+after	O
+the	O
+cessation	O
+of	O
+a	O
+7	O
+-	O
+year	O
+postnatal	O
+exposure	O
+(	O
+Rice	O
+1996	O
+)	O
+.	O
+
+Metallothionein	O
+(	O
+MT	O
+)	O
+protects	O
+against	O
+the	O
+toxicities	O
+of	O
+a	O
+variety	O
+of	O
+metals	O
+.	O
+
+We	O
+examined	O
+the	O
+neurotoxicity	O
+and	O
+developmental	O
+toxicity	O
+of	O
+metallic	O
+Hg	O
+in	O
+MT	O
+I	O
+/	O
+II	O
+-	O
+knockout	O
+mice	B
+(	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+and	O
+demonstrated	O
+the	O
+susceptibility	O
+of	O
+this	O
+genetically	O
+manipulated	O
+strain	O
+to	O
+the	O
+toxicity	O
+of	O
+metallic	O
+Hg	O
+.	O
+
+In	O
+contrast	O
+to	O
+metallic	O
+Hg	O
+,	O
+MeHg	O
+does	O
+not	O
+induce	O
+MT	O
+,	O
+and	O
+MT	O
+would	O
+not	O
+substantially	O
+influence	O
+the	O
+kinetics	O
+of	O
+MeHg	O
+(	O
+Yasutake	O
+et	O
+al	O
+.	O
+1998	O
+)	O
+.	O
+
+Several	O
+reports	O
+,	O
+however	O
+,	O
+have	O
+demonstrated	O
+protective	O
+effects	O
+of	O
+MT	O
+against	O
+MeHg	O
+toxicity	O
+,	O
+which	O
+was	O
+ascribed	O
+to	O
+the	O
+radical	O
+scavenging	O
+effect	O
+of	O
+MT	O
+(	O
+Yao	O
+et	O
+al	O
+.	O
+2000	O
+)	O
+.	O
+
+We	O
+also	O
+showed	O
+that	O
+perinatal	O
+exposure	O
+to	O
+MeHg	O
+results	O
+in	O
+altered	O
+metabolism	O
+of	O
+thyroid	O
+hormones	O
+in	O
+neonates	O
+that	O
+was	O
+more	O
+distinct	O
+in	O
+MT	O
+-	O
+null	O
+strains	O
+than	O
+their	O
+wild	O
+-	O
+type	O
+counterparts	O
+(	O
+Mori	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+The	O
+vulnerability	O
+of	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+suggests	O
+that	O
+delayed	O
+neurobehavioral	O
+toxicity	O
+due	O
+to	O
+MeHg	O
+,	O
+if	O
+it	O
+does	O
+exist	O
+,	O
+might	O
+be	O
+more	O
+distinctive	O
+in	O
+this	O
+strain	O
+.	O
+
+By	O
+utilizing	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+,	O
+we	O
+aimed	O
+to	O
+answer	O
+the	O
+following	O
+two	O
+questions	O
+:	O
+First	O
+,	O
+could	O
+we	O
+generate	O
+a	O
+model	O
+in	O
+which	O
+the	O
+toxicity	O
+of	O
+MeHg	O
+would	O
+emerge	O
+or	O
+at	O
+least	O
+become	O
+exaggerated	O
+later	O
+in	O
+life	O
+as	O
+opposed	O
+to	O
+earlier	O
+in	O
+life	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+at	O
+3	O
+-	O
+6	O
+months	O
+,	O
+which	O
+was	O
+the	O
+timing	O
+for	O
+most	O
+of	O
+the	O
+earlier	O
+studies	O
+that	O
+used	O
+behavioral	O
+evaluations	O
+)	O
+?	O
+
+Second	O
+,	O
+would	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+be	O
+affected	O
+more	O
+than	O
+its	O
+parent	O
+C57BL	O
+strain	O
+?	O
+
+Answering	O
+either	O
+of	O
+these	O
+questions	O
+not	O
+only	O
+could	O
+influence	O
+the	O
+risk	O
+evaluation	O
+of	O
+MeHg	O
+,	O
+but	O
+it	O
+could	O
+also	O
+lead	O
+to	O
+a	O
+better	O
+understanding	O
+of	O
+the	O
+mechanism	O
+of	O
+toxicity	O
+for	O
+perinatal	O
+MeHg	O
+exposure	O
+.	O
+
+To	O
+address	O
+these	O
+issues	O
+,	O
+we	O
+used	O
+three	O
+behavioral	O
+paradigms	O
+,	O
+the	O
+open	O
+field	O
+(	O
+OPF	O
+)	O
+,	O
+passive	O
+avoidance	O
+(	O
+PA	O
+)	O
+,	O
+and	O
+Morris	O
+(	O
+water	O
+)	O
+maze	O
+(	O
+MM	O
+)	O
+tests	O
+,	O
+which	O
+are	O
+often	O
+used	O
+in	O
+this	O
+field	O
+and	O
+which	O
+we	O
+used	O
+in	O
+our	O
+previous	O
+studies	O
+on	O
+the	O
+effects	O
+of	O
+Hg	O
+vapor	O
+(	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+,	O
+2006	O
+)	O
+.	O
+
+Performances	O
+in	O
+the	O
+MM	O
+and	O
+PA	O
+are	O
+said	O
+to	O
+be	O
+the	O
+most	O
+sensitive	O
+to	O
+aging	O
+(	O
+Gower	O
+and	O
+Lamberty	O
+1993	O
+)	O
+.	O
+
+We	O
+used	O
+a	O
+dose	O
+of	O
+5	O
+mu	O
+g	O
+MeHg	O
+/	O
+g	O
+in	O
+the	O
+diet	O
+,	O
+which	O
+resulted	O
+in	O
+a	O
+brain	O
+Hg	O
+level	O
+relevant	O
+to	O
+human	B
+risk	O
+assessment	O
+.	O
+
+We	O
+evaluated	O
+the	O
+behavioral	O
+end	O
+points	O
+twice	O
+,	O
+once	O
+around	O
+3	O
+months	O
+of	O
+age	O
+and	O
+the	O
+other	O
+time	O
+around	O
+1	O
+year	O
+;	O
+the	O
+latter	O
+time	O
+roughly	O
+corresponds	O
+to	O
+the	O
+period	O
+when	O
+many	O
+behavioral	O
+performances	O
+,	O
+including	O
+OPF	O
+(	O
+Acevedoa	O
+et	O
+al	O
+.	O
+2006	O
+;	O
+Carrie	O
+et	O
+al	O
+.	O
+1999	O
+;	O
+Gower	O
+and	O
+Lamberty	O
+1993	O
+)	O
+,	O
+PA	O
+(	O
+Gower	O
+and	O
+Lamberty	O
+1993	O
+)	O
+,	O
+and	O
+MM	O
+(	O
+Bach	O
+et	O
+al	O
+.	O
+1999	O
+;	O
+Carrie	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+,	O
+show	O
+alterations	O
+in	O
+this	O
+mouse	B
+strain	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Animals	O
+and	O
+MeHg	O
+exposure	O
+
+OLA129	O
+/	O
+C57BL	O
+/	O
+6J	O
+strain	O
+mice	B
+(	O
+wild	O
+type	O
+)	O
+and	O
+MT	O
+I	O
+/	O
+II	O
+-	O
+knockout	O
+mice	B
+(	O
+MT	O
+-	O
+null	O
+)	O
+of	O
+this	O
+strain	O
+were	O
+provided	O
+by	O
+K	O
+.	O
+H	O
+.	O
+
+Choo	O
+of	O
+the	O
+Murdoch	O
+Institute	O
+,	O
+Parkville	O
+,	O
+Australia	O
+(	O
+Michalska	O
+and	O
+Choo	O
+1993	O
+)	O
+and	O
+were	O
+of	O
+a	O
+mixed	O
+genetic	O
+background	O
+of	O
+129	O
+/	O
+Ola	O
+and	O
+C57BL	O
+/	O
+6	O
+strains	O
+.	O
+
+F1	O
+hybrid	O
+mice	B
+were	O
+mated	O
+with	O
+C57BL	O
+/	O
+6	O
+mice	B
+for	O
+six	O
+generations	O
+at	O
+the	O
+National	O
+Institute	O
+for	O
+Environmental	O
+Studies	O
+(	O
+Tsukuba	O
+,	O
+Japan	O
+)	O
+.	O
+
+At	O
+10	O
+weeks	O
+of	O
+age	O
+,	O
+single	O
+male	O
+and	O
+female	O
+mice	B
+were	O
+allowed	O
+to	O
+cohabit	O
+;	O
+every	O
+female	O
+mouse	B
+was	O
+checked	O
+each	O
+morning	O
+for	O
+the	O
+presence	O
+of	O
+a	O
+vaginal	O
+plug	O
+.	O
+
+When	O
+a	O
+plug	O
+was	O
+confirmed	O
+,	O
+the	O
+day	O
+was	O
+designated	O
+as	O
+day	O
+0	O
+of	O
+gestation	O
+(	O
+GD0	O
+)	O
+.	O
+
+The	O
+diet	O
+,	O
+NIH	O
+-	O
+07PLD	O
+formula	O
+(	O
+CLEA	O
+Japan	O
+,	O
+Inc	O
+.	O
+,	O
+Tokyo	O
+,	O
+Japan	O
+)	O
+,	O
+contained	O
+vitamins	O
+and	O
+trace	O
+elements	O
+as	O
+follows	O
+(	O
+per	O
+kilogram	O
+diet	O
+)	O
+:	O
+3	O
+.	O
+2	O
+mg	O
+CuSO4	O
+,	O
+88	O
+mg	O
+FeSO4	O
+,	O
+149	O
+mg	O
+MnSO4	O
+,	O
+25	O
+mg	O
+ZnCO3	O
+,	O
+1	O
+.	O
+6	O
+mg	O
+Ca	O
+(	O
+IO3	O
+)	O
+2	O
+,	O
+11	O
+mg	O
+vitamin	O
+B1	O
+,	O
+4	O
+.	O
+7	O
+mg	O
+vitamin	O
+B2	O
+,	O
+1	O
+.	O
+9	O
+mg	O
+vitamin	O
+B6	O
+,	O
+44	O
+mg	O
+vitamin	O
+E	O
+,	O
+in	O
+addition	O
+to	O
+5	O
+mu	O
+g	O
+MeHg	O
+/	O
+g	O
+.	O
+
+This	O
+diet	O
+was	O
+fed	O
+to	O
+the	O
+pregnant	O
+mice	B
+starting	O
+from	O
+GD0	O
+through	O
+10	O
+days	O
+after	O
+delivery	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+PND10	O
+)	O
+.	O
+
+Thereafter	O
+,	O
+we	O
+switched	O
+mice	B
+to	O
+a	O
+diet	O
+that	O
+did	O
+not	O
+contain	O
+MeHg	O
+.	O
+
+We	O
+chose	O
+GD0	O
+as	O
+the	O
+beginning	O
+of	O
+exposure	O
+because	O
+exposures	O
+that	O
+started	O
+before	O
+conception	O
+often	O
+resulted	O
+in	O
+fairly	O
+high	O
+Hg	O
+concentrations	O
+in	O
+fetal	O
+/	O
+neonatal	O
+brains	O
+(	O
+Kakita	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+,	O
+and	O
+we	O
+chose	O
+PND10	O
+to	O
+cover	O
+the	O
+early	O
+neonatal	O
+period	O
+,	O
+in	O
+which	O
+considerable	O
+brain	O
+growth	O
+occurs	O
+.	O
+
+In	O
+our	O
+experimental	O
+setting	O
+,	O
+the	O
+neonatal	O
+mice	B
+started	O
+to	O
+eat	O
+from	O
+the	O
+diet	O
+bucket	O
+and	O
+drink	O
+from	O
+the	O
+water	O
+bottle	O
+from	O
+PND10	O
+onward	O
+.	O
+
+Control	O
+mice	B
+were	O
+kept	O
+on	O
+the	O
+same	O
+diet	O
+but	O
+without	O
+MeHg	O
+(	O
+<	O
+0	O
+.	O
+01	O
+mu	O
+g	O
+Hg	O
+/	O
+g	O
+)	O
+.	O
+
+On	O
+PND1	O
+,	O
+to	O
+avoid	O
+the	O
+confounding	O
+effects	O
+due	O
+to	O
+different	O
+litter	O
+size	O
+,	O
+we	O
+reduced	O
+each	O
+litter	O
+to	O
+six	O
+pups	O
+(	O
+three	O
+males	O
+and	O
+three	O
+females	O
+when	O
+possible	O
+)	O
+,	O
+and	O
+on	O
+PND10	O
+,	O
+two	O
+males	O
+and	O
+two	O
+females	O
+from	O
+each	O
+litter	O
+were	O
+killed	O
+for	O
+chemical	O
+analyses	O
+.	O
+
+The	O
+remaining	O
+male	O
+and	O
+female	O
+offspring	O
+per	O
+litter	O
+were	O
+weaned	O
+on	O
+PND28	O
+and	O
+used	O
+for	O
+subsequent	O
+behavioral	O
+analyses	O
+(	O
+either	O
+at	O
+12	O
+-	O
+13	O
+weeks	O
+or	O
+52	O
+-	O
+53	O
+weeks	O
+,	O
+depending	O
+on	O
+the	O
+litter	O
+)	O
+as	O
+described	O
+below	O
+.	O
+
+We	O
+measured	O
+body	O
+weights	O
+of	O
+the	O
+weaned	O
+mice	B
+every	O
+2	O
+weeks	O
+.	O
+
+Thus	O
+,	O
+four	O
+experimental	O
+groups	O
+were	O
+used	O
+(	O
+with	O
+or	O
+without	O
+MeHg	O
+exposure	O
+for	O
+two	O
+strains	O
+)	O
+,	O
+and	O
+each	O
+group	O
+consisted	O
+of	O
+12	O
+-	O
+13	O
+litters	O
+.	O
+
+For	O
+half	O
+of	O
+the	O
+litters	O
+,	O
+the	O
+behavioral	O
+analyses	O
+were	O
+conducted	O
+at	O
+12	O
+-	O
+13	O
+weeks	O
+of	O
+age	O
+,	O
+and	O
+upon	O
+completion	O
+of	O
+the	O
+behavioral	O
+analyses	O
+,	O
+the	O
+animals	O
+were	O
+killed	O
+under	O
+ether	O
+anesthesia	O
+.	O
+
+We	O
+then	O
+dissected	O
+the	O
+organs	O
+(	O
+brain	O
+,	O
+liver	O
+,	O
+and	O
+kidneys	O
+)	O
+for	O
+Hg	O
+analyses	O
+.	O
+
+For	O
+the	O
+remaining	O
+half	O
+of	O
+the	O
+litters	O
+,	O
+we	O
+conducted	O
+the	O
+behavioral	O
+tests	O
+at	O
+52	O
+-	O
+53	O
+weeks	O
+of	O
+age	O
+.	O
+
+The	O
+mice	B
+were	O
+treated	O
+humanely	O
+and	O
+with	O
+regard	O
+to	O
+alleviation	O
+of	O
+suffering	O
+according	O
+to	O
+the	O
+National	O
+Institute	O
+for	O
+Environmental	O
+Studies	O
+'	O
+Guidelines	O
+for	O
+Animal	O
+Welfare	O
+and	O
+the	O
+guidelines	O
+of	O
+St	O
+.	O
+
+Marianna	O
+University	O
+.	O
+
+Behavioral	O
+evaluations	O
+
+The	O
+details	O
+of	O
+each	O
+behavioral	O
+procedure	O
+have	O
+been	O
+described	O
+elsewhere	O
+(	O
+Yoshida	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Brief	O
+descriptions	O
+follow	O
+.	O
+
+For	O
+the	O
+OPF	O
+test	O
+,	O
+we	O
+used	O
+an	O
+OPF	O
+apparatus	O
+(	O
+Ohara	O
+Co	O
+.	O
+,	O
+Ltd	O
+.	O
+,	O
+Tokyo	O
+,	O
+Japan	O
+)	O
+with	O
+a	O
+60	O
+x	O
+60	O
+-	O
+cm	O
+floor	O
+surrounded	O
+by	O
+walls	O
+60	O
+cm	O
+high	O
+.	O
+
+The	O
+experimental	O
+room	O
+light	O
+was	O
+turned	O
+off	O
+,	O
+and	O
+a	O
+dim	O
+light	O
+of	O
+80	O
+lux	O
+was	O
+lit	O
+during	O
+the	O
+experiment	O
+.	O
+
+We	O
+placed	O
+a	O
+mouse	B
+in	O
+the	O
+center	O
+of	O
+the	O
+floor	O
+and	O
+monitored	O
+its	O
+behavior	O
+for	O
+10	O
+min	O
+using	O
+a	O
+CCD	O
+camera	O
+connected	O
+to	O
+a	O
+computer	O
+.	O
+
+The	O
+position	O
+of	O
+the	O
+center	O
+of	O
+gravity	O
+was	O
+calculated	O
+by	O
+image	O
+-	O
+analyzing	O
+software	O
+,	O
+which	O
+was	O
+used	O
+to	O
+calculate	O
+the	O
+total	O
+distance	O
+traveled	O
+by	O
+the	O
+mouse	B
+as	O
+well	O
+as	O
+the	O
+positional	O
+preference	O
+(	O
+either	O
+center	O
+or	O
+peripheral	O
+,	O
+where	O
+peripheral	O
+was	O
+defined	O
+as	O
+the	O
+area	O
+within	O
+10	O
+cm	O
+from	O
+the	O
+wall	O
+)	O
+.	O
+
+We	O
+cleaned	O
+the	O
+OPF	O
+apparatus	O
+with	O
+70	O
+%	O
+ethanol	O
+between	O
+trials	O
+.	O
+
+The	O
+apparatus	O
+for	O
+the	O
+PA	O
+test	O
+(	O
+Ohara	O
+Co	O
+.	O
+Ltd	O
+.	O
+)	O
+consisted	O
+of	O
+a	O
+light	O
+compartment	O
+that	O
+illuminated	O
+by	O
+a	O
+400	O
+-	O
+lux	O
+light	O
+and	O
+a	O
+dark	O
+compartment	O
+with	O
+black	O
+opaque	O
+walls	O
+and	O
+lids	O
+.	O
+
+The	O
+two	O
+compartments	O
+were	O
+separated	O
+by	O
+a	O
+mobile	O
+guillotine	O
+door	O
+.	O
+
+On	O
+the	O
+first	O
+day	O
+(	O
+training	O
+trial	O
+)	O
+,	O
+we	O
+placed	O
+each	O
+mouse	B
+in	O
+the	O
+light	O
+compartment	O
+facing	O
+away	O
+from	O
+the	O
+guillotine	O
+door	O
+,	O
+which	O
+was	O
+closed	O
+.	O
+
+After	O
+30	O
+sec	O
+of	O
+introduction	O
+,	O
+the	O
+door	O
+was	O
+opened	O
+;	O
+when	O
+the	O
+mouse	B
+entered	O
+the	O
+dark	O
+compartment	O
+,	O
+a	O
+brief	O
+electric	O
+shock	O
+(	O
+4	O
+mA	O
+for	O
+2	O
+sec	O
+)	O
+was	O
+delivered	O
+through	O
+the	O
+metal	O
+grid	O
+floor	O
+.	O
+
+This	O
+would	O
+force	O
+the	O
+mouse	B
+back	O
+to	O
+the	O
+light	O
+component	O
+.	O
+
+The	O
+interval	O
+between	O
+the	O
+opening	O
+of	O
+the	O
+door	O
+and	O
+the	O
+entry	O
+to	O
+the	O
+dark	O
+room	O
+(	O
+in	O
+seconds	O
+)	O
+was	O
+recorded	O
+and	O
+defined	O
+as	O
+the	O
+latency	O
+.	O
+
+On	O
+the	O
+next	O
+day	O
+,	O
+the	O
+same	O
+procedure	O
+was	O
+repeated	O
+,	O
+but	O
+without	O
+the	O
+electric	O
+shock	O
+(	O
+retaining	O
+trail	O
+)	O
+.	O
+
+In	O
+this	O
+PA	O
+paradigm	O
+,	O
+aversive	O
+learning	O
+was	O
+assumed	O
+to	O
+be	O
+established	O
+in	O
+the	O
+training	O
+trial	O
+,	O
+and	O
+we	O
+used	O
+its	O
+retention	O
+in	O
+the	O
+retaining	O
+trail	O
+as	O
+the	O
+index	O
+of	O
+learning	O
+.	O
+
+Between	O
+each	O
+individual	O
+trial	O
+,	O
+we	O
+cleaned	O
+the	O
+apparatus	O
+with	O
+ethanol	O
+.	O
+
+The	O
+cutoff	O
+time	O
+of	O
+the	O
+retention	O
+session	O
+was	O
+300	O
+sec	O
+.	O
+
+The	O
+MM	O
+test	O
+apparatus	O
+(	O
+Ohara	O
+Co	O
+.	O
+,	O
+Ltd	O
+.	O
+)	O
+was	O
+a	O
+round	O
+-	O
+shaped	O
+water	O
+pool	O
+with	O
+a	O
+diameter	O
+of	O
+120	O
+cm	O
+.	O
+
+A	O
+small	O
+platform	O
+was	O
+submerged	O
+in	O
+the	O
+water	O
+,	O
+which	O
+provided	O
+a	O
+place	O
+for	O
+mice	B
+to	O
+escape	O
+from	O
+the	O
+water	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+an	O
+aversive	O
+stimulus	O
+,	O
+water	O
+temperature	O
+=	O
+23	O
++	O
+/	O
+-	O
+1	O
+degrees	O
+C	O
+)	O
+.	O
+
+The	O
+water	O
+was	O
+made	O
+opaque	O
+by	O
+adding	O
+white	O
+paint	O
+so	O
+that	O
+the	O
+mouse	B
+could	O
+not	O
+see	O
+the	O
+submerged	O
+platform	O
+.	O
+
+In	O
+each	O
+trial	O
+,	O
+we	O
+released	O
+a	O
+mouse	B
+into	O
+the	O
+pool	O
+from	O
+a	O
+determined	O
+position	O
+along	O
+the	O
+wall	O
+,	O
+and	O
+the	O
+performance	O
+of	O
+the	O
+mouse	B
+was	O
+monitored	O
+by	O
+a	O
+CCD	O
+camera	O
+/	O
+image	O
+analyzer	O
+.	O
+
+The	O
+time	O
+required	O
+to	O
+reach	O
+the	O
+platform	O
+was	O
+recorded	O
+.	O
+
+If	O
+a	O
+mouse	B
+could	O
+not	O
+find	O
+the	O
+platform	O
+within	O
+60	O
+sec	O
+after	O
+release	O
+,	O
+it	O
+was	O
+led	O
+to	O
+the	O
+platform	O
+and	O
+placed	O
+on	O
+it	O
+for	O
+20	O
+sec	O
+before	O
+being	O
+removed	O
+.	O
+
+In	O
+these	O
+cases	O
+,	O
+a	O
+latency	O
+of	O
+60	O
+sec	O
+was	O
+recorded	O
+.	O
+
+We	O
+conducted	O
+the	O
+trial	O
+once	O
+a	O
+day	O
+up	O
+to	O
+the	O
+fifth	O
+day	O
+for	O
+each	O
+mouse	B
+,	O
+and	O
+the	O
+order	O
+of	O
+each	O
+mouse	B
+was	O
+counterbalanced	O
+across	O
+the	O
+day	O
+.	O
+
+On	O
+the	O
+sixth	O
+day	O
+,	O
+a	O
+transfer	O
+test	O
+(	O
+or	O
+probe	O
+test	O
+)	O
+,	O
+which	O
+is	O
+a	O
+trial	O
+without	O
+the	O
+platform	O
+,	O
+was	O
+conducted	O
+;	O
+in	O
+this	O
+procedure	O
+,	O
+we	O
+counted	O
+the	O
+number	O
+of	O
+times	O
+that	O
+the	O
+mouse	B
+crossed	O
+the	O
+position	O
+where	O
+the	O
+platform	O
+had	O
+been	O
+.	O
+
+Tissue	O
+Hg	O
+concentration	O
+
+The	O
+tissue	O
+samples	O
+were	O
+homogenized	O
+(	O
+10	O
+%	O
+weight	O
+/	O
+volume	O
+)	O
+in	O
+distilled	O
+water	O
+using	O
+a	O
+Polytron	O
+homogenizer	O
+(	O
+Kinematica	O
+GmbH	O
+,	O
+Littau	O
+,	O
+Switzerland	O
+)	O
+.	O
+
+We	O
+determined	O
+Hg	O
+levels	O
+in	O
+the	O
+homogenates	O
+by	O
+the	O
+oxygen	O
+combustion	O
+-	O
+gold	O
+amalgamation	O
+method	O
+(	O
+Ohkawa	O
+et	O
+al	O
+.	O
+1977	O
+)	O
+using	O
+an	O
+atomic	O
+absorption	O
+Hg	O
+detector	O
+MD	O
+-	O
+1	O
+(	O
+Nippon	O
+Instruments	O
+,	O
+Co	O
+.	O
+Ltd	O
+.	O
+,	O
+Osaka	O
+,	O
+Japan	O
+)	O
+.	O
+
+To	O
+ensure	O
+the	O
+accuracy	O
+of	O
+the	O
+measurement	O
+,	O
+we	O
+included	O
+reference	O
+material	O
+from	O
+a	O
+dogfish	O
+(	O
+DORM	O
+-	O
+2	O
+;	O
+National	O
+Research	O
+Council	O
+of	O
+Canada	O
+,	O
+Ottawa	O
+,	O
+Ontario	O
+,	O
+Canada	O
+)	O
+with	O
+a	O
+certified	O
+value	O
+of	O
+4	O
+.	O
+64	O
++	O
+/	O
+-	O
+0	O
+.	O
+26	O
+mu	O
+g	O
+/	O
+g	O
+in	O
+the	O
+analyses	O
+;	O
+the	O
+observed	O
+values	O
+fell	O
+within	O
+the	O
+certified	O
+range	O
+.	O
+
+The	O
+detection	O
+limit	O
+of	O
+the	O
+measurement	O
+was	O
+0	O
+.	O
+1	O
+ng	O
+Hg	O
+.	O
+
+Statistics	O
+
+We	O
+analyzed	O
+behavioral	O
+data	O
+for	O
+OPF	O
+and	O
+PA	O
+by	O
+analysis	O
+of	O
+variance	O
+(	O
+ANOVA	O
+)	O
+,	O
+taking	O
+sex	O
+,	O
+strain	O
+,	O
+and	O
+MeHg	O
+exposure	O
+as	O
+the	O
+factors	O
+.	O
+
+All	O
+the	O
+interactions	O
+among	O
+these	O
+factors	O
+were	O
+put	O
+into	O
+the	O
+model	O
+.	O
+
+When	O
+any	O
+of	O
+the	O
+interactions	O
+was	O
+highly	O
+significant	O
+,	O
+we	O
+analyzed	O
+the	O
+data	O
+separately	O
+in	O
+an	O
+appropriate	O
+way	O
+;	O
+for	O
+example	O
+,	O
+if	O
+sex	O
+x	O
+Hg	O
+was	O
+significant	O
+,	O
+the	O
+data	O
+for	O
+males	O
+and	O
+females	O
+were	O
+separately	O
+analyzed	O
+for	O
+the	O
+effects	O
+of	O
+strain	O
+and	O
+Hg	O
+.	O
+
+Whenever	O
+appropriate	O
+,	O
+ANOVAs	O
+were	O
+followed	O
+by	O
+Mann	O
+-	O
+Whitney	O
+U	O
+or	O
+Student	O
+'	O
+s	O
+t	O
+-	O
+tests	O
+,	O
+depending	O
+on	O
+the	O
+nature	O
+and	O
+distribution	O
+of	O
+the	O
+variables	O
+.	O
+
+We	O
+analyzed	O
+data	O
+for	O
+the	O
+MM	O
+by	O
+repeated	O
+-	O
+measures	O
+ANOVA	O
+,	O
+taking	O
+the	O
+exposure	O
+as	O
+between	O
+-	O
+group	O
+and	O
+trials	O
+as	O
+within	O
+-	O
+group	O
+variables	O
+.	O
+
+The	O
+test	O
+was	O
+performed	O
+for	O
+each	O
+of	O
+the	O
+four	O
+sex	O
+and	O
+strain	O
+combinations	O
+separately	O
+.	O
+
+The	O
+significance	O
+level	O
+was	O
+set	O
+at	O
+p	O
+<	O
+0	O
+.	O
+05	O
+.	O
+
+Results	O
+
+Body	O
+weight	O
+
+Up	O
+to	O
+20	O
+weeks	O
+of	O
+age	O
+,	O
+the	O
+body	O
+weight	O
+values	O
+of	O
+the	O
+control	O
+and	O
+MeHg	O
+-	O
+exposed	O
+groups	O
+were	O
+not	O
+different	O
+,	O
+regardless	O
+of	O
+strain	O
+or	O
+sex	O
+.	O
+
+After	O
+28	O
+weeks	O
+,	O
+except	O
+for	O
+the	O
+wild	O
+-	O
+type	O
+female	O
+groups	O
+,	O
+the	O
+MeHg	O
+-	O
+exposed	O
+groups	O
+weighed	O
+significantly	O
+less	O
+than	O
+the	O
+controls	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+OPF	O
+
+At	O
+12	O
+weeks	O
+of	O
+age	O
+,	O
+a	O
+three	O
+-	O
+way	O
+ANOVA	O
+of	O
+the	O
+locomotion	O
+distance	O
+revealed	O
+that	O
+only	O
+strain	O
+was	O
+a	O
+significant	O
+factor	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+,	O
+reflecting	O
+the	O
+longer	O
+distance	O
+traveled	O
+by	O
+the	O
+MT	O
+-	O
+null	O
+mice	B
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+Strain	O
+was	O
+also	O
+a	O
+significant	O
+factor	O
+for	O
+the	O
+proportion	O
+of	O
+the	O
+central	O
+-	O
+area	O
+locomotion	O
+(	O
+Figure	O
+3A	O
+)	O
+,	O
+and	O
+Hg	O
+exposure	O
+marginally	O
+affected	O
+this	O
+outcome	O
+.	O
+
+In	O
+MT	O
+-	O
+null	O
+females	O
+,	O
+the	O
+proportion	O
+of	O
+central	O
+-	O
+area	O
+locomotion	O
+was	O
+higher	O
+in	O
+MeHg	O
+-	O
+exposed	O
+mice	B
+than	O
+in	O
+the	O
+controls	O
+;	O
+this	O
+difference	O
+was	O
+not	O
+observed	O
+in	O
+any	O
+other	O
+strain	O
+-	O
+sex	O
+combination	O
+.	O
+
+At	O
+52	O
+weeks	O
+of	O
+age	O
+,	O
+the	O
+strain	O
+x	O
+Hg	O
+interaction	O
+was	O
+highly	O
+significant	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+an	O
+ANOVA	O
+of	O
+locomotion	O
+distance	O
+(	O
+Figure	O
+2B	O
+)	O
+;	O
+MeHg	O
+exposure	O
+was	O
+associated	O
+with	O
+decreased	O
+locomotion	O
+distance	O
+in	O
+wild	O
+-	O
+type	O
+mice	B
+and	O
+with	O
+increased	O
+distance	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+.	O
+
+A	O
+strain	O
+-	O
+wise	O
+two	O
+-	O
+way	O
+ANOVA	O
+(	O
+with	O
+sex	O
+and	O
+Hg	O
+as	O
+the	O
+factors	O
+)	O
+revealed	O
+that	O
+only	O
+Hg	O
+was	O
+significant	O
+in	O
+both	O
+strains	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+.	O
+
+Regarding	O
+the	O
+proportion	O
+of	O
+the	O
+central	O
+-	O
+area	O
+locomotion	O
+,	O
+the	O
+effects	O
+of	O
+MeHg	O
+appeared	O
+to	O
+depend	O
+on	O
+sex	O
+[	O
+i	O
+.	O
+e	O
+.	O
+,	O
+sex	O
+x	O
+Hg	O
+was	O
+highly	O
+significant	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+the	O
+three	O
+-	O
+way	O
+ANOVA	O
+;	O
+Figure	O
+3B	O
+]	O
+.	O
+
+Indeed	O
+,	O
+a	O
+sex	O
+-	O
+wise	O
+two	O
+-	O
+way	O
+ANOVA	O
+showed	O
+significant	O
+effects	O
+of	O
+Hg	O
+only	O
+in	O
+females	O
+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+PA	O
+
+At	O
+12	O
+weeks	O
+of	O
+age	O
+,	O
+all	O
+the	O
+groups	O
+showed	O
+prolonged	O
+latency	O
+in	O
+the	O
+second	O
+(	O
+retention	O
+)	O
+trial	O
+,	O
+and	O
+no	O
+consistent	O
+effect	O
+of	O
+MeHg	O
+was	O
+recognized	O
+regardless	O
+of	O
+strain	O
+or	O
+sex	O
+(	O
+Figure	O
+4A	O
+)	O
+.	O
+
+At	O
+52	O
+weeks	O
+of	O
+age	O
+,	O
+a	O
+three	O
+-	O
+way	O
+ANOVA	O
+revealed	O
+a	O
+significant	O
+interaction	O
+between	O
+strain	O
+and	O
+Hg	O
+(	O
+p	O
+<	O
+0	O
+.	O
+05	O
+)	O
+;	O
+strain	O
+-	O
+wise	O
+two	O
+-	O
+way	O
+ANOVAs	O
+revealed	O
+a	O
+significant	O
+effect	O
+of	O
+Hg	O
+on	O
+learning	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+of	O
+both	O
+sexes	O
+;	O
+these	O
+groups	O
+of	O
+mice	B
+showed	O
+significantly	O
+shorter	O
+(	O
+less	O
+than	O
+half	O
+)	O
+latency	O
+times	O
+compared	O
+to	O
+control	O
+mice	B
+(	O
+Figure	O
+4B	O
+)	O
+.	O
+
+A	O
+notable	O
+difference	O
+between	O
+the	O
+results	O
+at	O
+52	O
+weeks	O
+of	O
+age	O
+and	O
+those	O
+at	O
+12	O
+weeks	O
+was	O
+that	O
+many	O
+of	O
+the	O
+tested	O
+mice	B
+exceeded	O
+the	O
+cutoff	O
+time	O
+in	O
+the	O
+retention	O
+trials	O
+at	O
+52	O
+weeks	O
+,	O
+except	O
+for	O
+the	O
+MT	O
+-	O
+null	O
+groups	O
+.	O
+
+MM	O
+
+At	O
+13	O
+weeks	O
+of	O
+age	O
+,	O
+repeated	O
+-	O
+measures	O
+ANOVA	O
+did	O
+not	O
+indicate	O
+any	O
+effects	O
+of	O
+MeHg	O
+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+At	O
+52	O
+weeks	O
+of	O
+age	O
+(	O
+Figure	O
+5B	O
+)	O
+,	O
+wild	O
+-	O
+type	O
+males	O
+and	O
+MT	O
+-	O
+null	O
+females	O
+shared	O
+the	O
+same	O
+statistical	O
+results	O
+;	O
+Hg	O
+as	O
+well	O
+as	O
+the	O
+Hg	O
+x	O
+trial	O
+interaction	O
+were	O
+statistically	O
+significant	O
+.	O
+
+Thus	O
+,	O
+in	O
+both	O
+cases	O
+,	O
+the	O
+MeHg	O
+groups	O
+showed	O
+a	O
+longer	O
+latency	O
+,	O
+hampering	O
+learning	O
+performance	O
+.	O
+
+Tissue	O
+Hg	O
+concentration	O
+
+At	O
+PND10	O
+,	O
+which	O
+was	O
+immediately	O
+after	O
+the	O
+exposure	O
+,	O
+brain	O
+Hg	O
+concentrations	O
+of	O
+the	O
+neonatal	O
+mice	B
+were	O
+approximately	O
+<	O
+=	O
+0	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Although	O
+the	O
+MT	O
+-	O
+null	O
+mice	B
+and	O
+females	O
+showed	O
+slightly	O
+higher	O
+brain	O
+Hg	O
+concentrations	O
+than	O
+the	O
+corresponding	O
+wild	O
+-	O
+type	O
+group	O
+and	O
+males	O
+,	O
+respectively	O
+,	O
+neither	O
+of	O
+these	O
+differences	O
+was	O
+significant	O
+.	O
+
+At	O
+13	O
+weeks	O
+,	O
+when	O
+the	O
+behavioral	O
+tests	O
+were	O
+completed	O
+,	O
+the	O
+brain	O
+Hg	O
+concentration	O
+was	O
+comparable	O
+to	O
+the	O
+control	O
+(	O
+nonexposed	O
+)	O
+level	O
+(	O
+approximately	O
+5	O
+ng	O
+/	O
+g	O
+in	O
+both	O
+the	O
+exposed	O
+and	O
+control	O
+brains	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+MT	O
+-	O
+null	O
+mice	B
+had	O
+a	O
+significantly	O
+lower	O
+brain	O
+Hg	O
+concentration	O
+than	O
+the	O
+corresponding	O
+wild	O
+-	O
+type	O
+groups	O
+.	O
+
+Discussion	O
+
+Results	O
+of	O
+the	O
+present	O
+study	O
+demonstrate	O
+the	O
+delayed	O
+emergence	O
+of	O
+neurobehavioral	O
+toxicity	O
+due	O
+to	O
+perinatal	O
+MeHg	O
+exposure	O
+,	O
+which	O
+presumably	O
+developed	O
+after	O
+brain	O
+MeHg	O
+concentrations	O
+had	O
+leveled	O
+off	O
+.	O
+
+This	O
+emergent	O
+toxicity	O
+was	O
+exaggerated	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+and	O
+was	O
+more	O
+distinct	O
+in	O
+females	O
+.	O
+
+To	O
+our	O
+knowledge	O
+,	O
+our	O
+findings	O
+show	O
+the	O
+first	O
+clear	O
+-	O
+cut	O
+demonstrations	O
+of	O
+a	O
+long	O
+latency	O
+period	O
+of	O
+MeHg	O
+neurobehavioral	O
+toxicity	O
+in	O
+rodents	O
+and	O
+possible	O
+genetic	O
+susceptibility	O
+for	O
+the	O
+emergent	O
+toxicity	O
+.	O
+
+The	O
+exposure	O
+level	O
+should	O
+be	O
+considered	O
+before	O
+discussing	O
+the	O
+end	O
+points	O
+.	O
+
+On	O
+PND10	O
+,	O
+immediately	O
+after	O
+the	O
+cessation	O
+of	O
+MeHg	O
+exposure	O
+,	O
+the	O
+brain	O
+Hg	O
+concentration	O
+was	O
+approximately	O
+0	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+,	O
+regardless	O
+of	O
+the	O
+strain	O
+or	O
+sex	O
+.	O
+
+In	O
+a	O
+previous	O
+study	O
+,	O
+the	O
+brain	O
+Hg	O
+concentration	O
+in	O
+mice	B
+perinatally	O
+exposed	O
+to	O
+6	O
+mg	O
+MeHg	O
+/	O
+L	O
+(	O
+via	O
+water	O
+)	O
+peaked	O
+between	O
+PND0	O
+and	O
+PND4	O
+and	O
+was	O
+approximately	O
+three	O
+times	O
+higher	O
+than	O
+on	O
+PND21	O
+(	O
+Goulet	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Therefore	O
+,	O
+the	O
+peak	O
+brain	O
+Hg	O
+concentration	O
+,	O
+which	O
+is	O
+presumably	O
+observed	O
+around	O
+birth	O
+,	O
+can	O
+be	O
+estimated	O
+as	O
+about	O
+3	O
+-	O
+fold	O
+higher	O
+than	O
+that	O
+on	O
+PND10	O
+and	O
+would	O
+be	O
+approximately	O
+1	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+(	O
+0	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+x	O
+3	O
+)	O
+,	O
+which	O
+is	O
+one	O
+of	O
+the	O
+lowest	O
+levels	O
+among	O
+recent	O
+rodent	O
+studies	O
+.	O
+
+As	O
+shown	O
+by	O
+Sakamoto	O
+et	O
+al	O
+.	O
+
+(	O
+2002	O
+)	O
+in	O
+their	O
+Figure	O
+2	O
+,	O
+prenatal	O
+exposure	O
+of	O
+rats	B
+to	O
+MeHg	O
+showed	O
+a	O
+peak	O
+brain	O
+Hg	O
+concentration	O
+around	O
+PND1	O
+that	O
+was	O
+four	O
+to	O
+five	O
+times	O
+greater	O
+than	O
+the	O
+level	O
+on	O
+PND10	O
+.	O
+
+Also	O
+,	O
+Newland	O
+and	O
+Rasmussen	O
+(	O
+2000	O
+)	O
+reported	O
+a	O
+slight	O
+alteration	O
+of	O
+a	O
+complex	O
+operant	O
+behavior	O
+in	O
+rats	B
+at	O
+ages	O
+<	O
+2	O
+years	O
+at	O
+brain	O
+Hg	O
+concentrations	O
+as	O
+low	O
+as	O
+0	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+at	O
+birth	O
+,	O
+although	O
+statistical	O
+significance	O
+of	O
+this	O
+particular	O
+effect	O
+was	O
+not	O
+clear	O
+.	O
+
+It	O
+should	O
+be	O
+noted	O
+that	O
+rats	B
+have	O
+different	O
+Hg	O
+kinetics	O
+(	O
+Hirayama	O
+and	O
+Yasutake	O
+1986	O
+;	O
+Yasutake	O
+and	O
+Hirayama	O
+1990	O
+)	O
+due	O
+to	O
+the	O
+high	O
+affinity	O
+of	O
+rat	O
+hemoglobin	O
+for	O
+MeHg	O
+(	O
+Clarkson	O
+and	O
+Magos	O
+2006	O
+)	O
+.	O
+
+The	O
+most	O
+important	O
+observation	O
+of	O
+the	O
+present	O
+study	O
+was	O
+that	O
+the	O
+effects	O
+of	O
+low	O
+-	O
+level	O
+MeHg	O
+exposure	O
+were	O
+detected	O
+only	O
+at	O
+later	O
+stages	O
+in	O
+the	O
+lives	O
+of	O
+the	O
+mice	B
+.	O
+
+Except	O
+for	O
+the	O
+central	O
+-	O
+area	O
+occupancy	O
+in	O
+OPF	O
+in	O
+MT	O
+-	O
+null	O
+females	O
+,	O
+no	O
+statistically	O
+significant	O
+effects	O
+of	O
+MeHg	O
+were	O
+observed	O
+in	O
+any	O
+of	O
+the	O
+three	O
+behavioral	O
+tests	O
+at	O
+12	O
+weeks	O
+of	O
+age	O
+.	O
+
+In	O
+contrast	O
+,	O
+significant	O
+effects	O
+were	O
+observed	O
+in	O
+all	O
+three	O
+tests	O
+at	O
+52	O
+weeks	O
+of	O
+age	O
+.	O
+
+The	O
+brain	O
+Hg	O
+concentration	O
+of	O
+the	O
+exposed	O
+groups	O
+had	O
+leveled	O
+off	O
+and	O
+was	O
+not	O
+distinguishable	O
+from	O
+the	O
+non	O
+-	O
+exposed	O
+group	O
+at	O
+13	O
+weeks	O
+of	O
+age	O
+,	O
+immediately	O
+after	O
+the	O
+first	O
+phase	O
+of	O
+the	O
+behavioral	O
+testing	O
+.	O
+
+Therefore	O
+,	O
+in	O
+the	O
+present	O
+study	O
+,	O
+there	O
+was	O
+a	O
+latency	O
+period	O
+in	O
+which	O
+the	O
+dose	O
+and	O
+effects	O
+could	O
+not	O
+be	O
+detected	O
+,	O
+although	O
+effects	O
+were	O
+observed	O
+9	O
+months	O
+later	O
+.	O
+
+Another	O
+notable	O
+observation	O
+was	O
+that	O
+the	O
+emergent	O
+manifestation	O
+of	O
+toxicity	O
+was	O
+also	O
+recognized	O
+in	O
+the	O
+suppression	O
+of	O
+body	O
+weight	O
+(	O
+except	O
+for	O
+wild	O
+-	O
+type	O
+females	O
+)	O
+,	O
+which	O
+only	O
+became	O
+apparent	O
+on	O
+or	O
+after	O
+28	O
+weeks	O
+of	O
+age	O
+.	O
+
+The	O
+existence	O
+of	O
+a	O
+latency	O
+period	O
+of	O
+as	O
+long	O
+as	O
+several	O
+years	O
+after	O
+chronic	O
+(	O
+7	O
+years	O
+from	O
+birth	O
+)	O
+,	O
+low	O
+-	O
+level	O
+exposure	O
+to	O
+MeHg	O
+has	O
+been	O
+described	O
+in	O
+nonhuman	O
+primates	O
+(	O
+Rice	O
+1996	O
+)	O
+.	O
+
+In	O
+that	O
+case	O
+,	O
+however	O
+,	O
+the	O
+Hg	O
+concentration	O
+in	O
+the	O
+brain	O
+remained	O
+elevated	O
+,	O
+presumably	O
+as	O
+a	O
+result	O
+of	O
+the	O
+long	O
+exposure	O
+.	O
+
+Indeed	O
+,	O
+Rice	O
+(	O
+1996	O
+)	O
+argued	O
+that	O
+the	O
+minute	O
+amount	O
+of	O
+residual	O
+brain	O
+Hg	O
+could	O
+have	O
+caused	O
+the	O
+delayed	O
+toxicity	O
+.	O
+
+This	O
+was	O
+clearly	O
+not	O
+the	O
+case	O
+in	O
+the	O
+present	O
+study	O
+because	O
+the	O
+Hg	O
+concentration	O
+leveled	O
+off	O
+around	O
+the	O
+time	O
+of	O
+the	O
+first	O
+phase	O
+of	O
+the	O
+behavioral	O
+study	O
+.	O
+
+The	O
+absence	O
+of	O
+behavioral	O
+effects	O
+at	O
+12	O
+weeks	O
+of	O
+age	O
+ruled	O
+out	O
+the	O
+possibility	O
+that	O
+the	O
+residual	O
+behavioral	O
+effects	O
+were	O
+due	O
+to	O
+elevated	O
+Hg	O
+early	O
+in	O
+life	O
+.	O
+
+Therefore	O
+,	O
+the	O
+behavioral	O
+toxicity	O
+that	O
+surfaced	O
+at	O
+52	O
+weeks	O
+of	O
+age	O
+must	O
+have	O
+had	O
+its	O
+origin	O
+before	O
+the	O
+brain	O
+Hg	O
+concentration	O
+leveled	O
+off	O
+(	O
+at	O
+or	O
+before	O
+13	O
+weeks	O
+of	O
+age	O
+)	O
+,	O
+although	O
+the	O
+redistribution	O
+of	O
+Hg	O
+to	O
+the	O
+brain	O
+from	O
+other	O
+sites	O
+of	O
+deposition	O
+,	O
+such	O
+as	O
+the	O
+liver	O
+,	O
+cannot	O
+be	O
+completely	O
+excluded	O
+.	O
+
+The	O
+long	O
+silent	O
+period	O
+before	O
+the	O
+manifestations	O
+of	O
+toxicity	O
+emerged	O
+suggests	O
+that	O
+a	O
+slow	O
+process	O
+plays	O
+a	O
+role	O
+in	O
+this	O
+latent	O
+toxicity	O
+.	O
+
+Although	O
+an	O
+example	O
+of	O
+a	O
+slow	O
+process	O
+is	O
+aging	O
+,	O
+52	O
+weeks	O
+of	O
+age	O
+might	O
+not	O
+be	O
+sufficiently	O
+old	O
+for	O
+a	O
+mouse	B
+to	O
+be	O
+considered	O
+aged	O
+in	O
+the	O
+physiologic	O
+sense	O
+because	O
+C57BL	O
+/	O
+6	O
+mice	B
+have	O
+a	O
+relatively	O
+long	O
+life	O
+span	O
+among	O
+mouse	B
+strains	O
+[	O
+median	O
+survival	O
+of	O
+27	O
+-	O
+31	O
+months	O
+(	O
+Gower	O
+and	O
+Lamberty	O
+1993	O
+)	O
+]	O
+and	O
+a	O
+survival	O
+rate	O
+at	O
+18	O
+-	O
+19	O
+months	O
+as	O
+high	O
+as	O
+90	O
+%	O
+(	O
+Institute	O
+on	O
+Aging	O
+HP	O
+)	O
+(	O
+National	O
+Institute	O
+on	O
+Aging	O
+2008	O
+)	O
+.	O
+
+Nevertheless	O
+,	O
+various	O
+behavioral	O
+examinations	O
+have	O
+shown	O
+age	O
+-	O
+related	O
+changes	O
+in	O
+the	O
+performance	O
+of	O
+mice	B
+at	O
+approximately	O
+1	O
+year	O
+of	O
+age	O
+in	O
+the	O
+OPF	O
+(	O
+Acevedoa	O
+et	O
+al	O
+.	O
+2006	O
+;	O
+Carrie	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+,	O
+MM	O
+(	O
+Bach	O
+et	O
+al	O
+.	O
+1999	O
+;	O
+Carrie	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+,	O
+and	O
+PA	O
+(	O
+Gower	O
+and	O
+Lamberty	O
+1993	O
+)	O
+tests	O
+.	O
+
+The	O
+observed	O
+effects	O
+of	O
+MeHg	O
+,	O
+including	O
+the	O
+deterioration	O
+in	O
+the	O
+PA	O
+and	O
+MM	O
+and	O
+suppression	O
+in	O
+the	O
+OPF	O
+(	O
+in	O
+wild	O
+-	O
+type	O
+mice	B
+)	O
+,	O
+were	O
+consistent	O
+with	O
+these	O
+reported	O
+effects	O
+of	O
+aging	O
+on	O
+behavioral	O
+function	O
+(	O
+in	O
+the	O
+sense	O
+described	O
+above	O
+)	O
+,	O
+except	O
+for	O
+the	O
+increased	O
+OPF	O
+activity	O
+in	O
+the	O
+MT	O
+-	O
+null	O
+mice	B
+.	O
+
+Regardless	O
+of	O
+its	O
+neural	O
+basis	O
+,	O
+the	O
+basis	O
+of	O
+neurobehavioral	O
+toxicity	O
+should	O
+be	O
+sought	O
+in	O
+early	O
+life	O
+stages	O
+when	O
+the	O
+brain	O
+Hg	O
+concentration	O
+is	O
+highly	O
+elevated	O
+(	O
+approximately	O
+1	O
+.	O
+5	O
+mu	O
+g	O
+/	O
+g	O
+at	O
+its	O
+peak	O
+)	O
+.	O
+
+Some	O
+in	O
+vivo	O
+experiments	O
+have	O
+demonstrated	O
+several	O
+candidate	O
+mechanisms	O
+of	O
+perinatal	O
+exposure	O
+to	O
+MeHg	O
+,	O
+including	O
+abnormal	O
+migration	O
+of	O
+neurons	O
+and	O
+/	O
+or	O
+glias	O
+(	O
+Kakita	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Rodier	O
+et	O
+al	O
+.	O
+1984	O
+)	O
+,	O
+but	O
+at	O
+higher	O
+Hg	O
+concentrations	O
+.	O
+
+Using	O
+exactly	O
+the	O
+same	O
+exposure	O
+protocol	O
+as	O
+the	O
+present	O
+study	O
+,	O
+we	O
+found	O
+suppressed	O
+activity	O
+of	O
+type	O
+III	O
+iodo	O
+-	O
+thyronine	O
+deiodinase	O
+,	O
+a	O
+thyroid	O
+hormone	O
+-	O
+metabolizing	O
+enzyme	O
+,	O
+in	O
+the	O
+brains	O
+of	O
+PND10	O
+mouse	B
+neonates	O
+(	O
+Mori	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+,	O
+consistent	O
+with	O
+our	O
+previous	O
+study	O
+of	O
+higher	O
+MeHg	O
+doses	O
+(	O
+Watanabe	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+.	O
+
+This	O
+perturbation	O
+could	O
+be	O
+one	O
+of	O
+the	O
+candidate	O
+mechanisms	O
+responsible	O
+for	O
+the	O
+later	O
+anomalous	O
+behaviors	O
+because	O
+even	O
+a	O
+transient	O
+change	O
+in	O
+thyroid	O
+hormones	O
+during	O
+the	O
+critical	O
+period	O
+of	O
+perinatal	O
+life	O
+exerts	O
+long	O
+-	O
+term	O
+consequences	O
+(	O
+Auso	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+The	O
+effects	O
+of	O
+MeHg	O
+at	O
+52	O
+weeks	O
+of	O
+age	O
+were	O
+influenced	O
+by	O
+two	O
+potential	O
+modifying	O
+factors	O
+,	O
+sex	O
+and	O
+strain	O
+.	O
+
+In	O
+the	O
+OPF	O
+,	O
+while	O
+the	O
+locomotion	O
+was	O
+affected	O
+in	O
+both	O
+strains	O
+(	O
+although	O
+the	O
+direction	O
+was	O
+opposite	O
+)	O
+,	O
+center	O
+occupancy	O
+was	O
+significantly	O
+increased	O
+only	O
+in	O
+the	O
+MT	O
+-	O
+null	O
+mice	B
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+effects	O
+on	O
+PA	O
+were	O
+significant	O
+only	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+,	O
+whereas	O
+MeHg	O
+at	O
+a	O
+higher	O
+dose	O
+was	O
+reported	O
+to	O
+worsen	O
+PA	O
+performance	O
+in	O
+rats	B
+(	O
+6	O
+-	O
+8	O
+weeks	O
+of	O
+age	O
+;	O
+Sakamoto	O
+et	O
+al	O
+.	O
+2002	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+body	O
+weight	O
+gain	O
+was	O
+suppressed	O
+in	O
+both	O
+male	O
+and	O
+female	O
+MT	O
+-	O
+null	O
+mice	B
+,	O
+whereas	O
+in	O
+wild	O
+-	O
+type	O
+mice	B
+the	O
+suppression	O
+was	O
+observed	O
+only	O
+in	O
+males	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+appeared	O
+to	O
+be	O
+slightly	O
+more	O
+susceptible	O
+to	O
+the	O
+late	O
+-	O
+emergent	O
+effects	O
+of	O
+MeHg	O
+.	O
+
+Several	O
+lines	O
+of	O
+evidence	O
+have	O
+shown	O
+that	O
+MT	O
+-	O
+I	O
+,	O
+II	O
+is	O
+protective	O
+against	O
+the	O
+toxicity	O
+of	O
+MeHg	O
+(	O
+Leiva	O
+-	O
+Presa	O
+et	O
+al	O
+.	O
+2004	O
+;	O
+Yao	O
+et	O
+al	O
+.	O
+2000	O
+)	O
+,	O
+and	O
+the	O
+present	O
+results	O
+were	O
+basically	O
+consistent	O
+with	O
+these	O
+reports	O
+.	O
+
+We	O
+have	O
+also	O
+reported	O
+the	O
+susceptibility	O
+of	O
+the	O
+MT	O
+-	O
+null	O
+strain	O
+to	O
+the	O
+neurotoxic	O
+effects	O
+of	O
+metallic	O
+Hg	O
+(	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+,	O
+2006	O
+)	O
+.	O
+
+The	O
+difference	O
+in	O
+the	O
+susceptibility	O
+to	O
+MeHg	O
+between	O
+sexes	O
+is	O
+still	O
+debated	O
+(	O
+Clarkson	O
+and	O
+Magos	O
+2006	O
+;	O
+National	O
+Research	O
+Council	O
+2000	O
+;	O
+Vahter	O
+2007	O
+)	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+some	O
+responses	O
+to	O
+MeHg	O
+were	O
+different	O
+between	O
+the	O
+sexes	O
+,	O
+including	O
+OPF	O
+performance	O
+at	O
+12	O
+and	O
+52	O
+weeks	O
+of	O
+age	O
+and	O
+MM	O
+performance	O
+at	O
+52	O
+weeks	O
+.	O
+
+The	O
+fact	O
+that	O
+the	O
+MT	O
+-	O
+null	O
+female	O
+group	O
+was	O
+the	O
+only	O
+group	O
+affected	O
+by	O
+MeHg	O
+at	O
+12	O
+weeks	O
+may	O
+suggest	O
+the	O
+particular	O
+susceptibility	O
+of	O
+females	O
+in	O
+this	O
+strain	O
+.	O
+
+This	O
+point	O
+needs	O
+to	O
+be	O
+clarified	O
+in	O
+further	O
+experiments	O
+.	O
+
+The	O
+question	O
+remains	O
+of	O
+why	O
+MT	O
+-	O
+null	O
+mice	B
+are	O
+susceptible	O
+to	O
+the	O
+delayed	O
+neurotoxicity	O
+of	O
+perinatal	O
+MeHg	O
+.	O
+
+Apparently	O
+kinetics	O
+play	O
+only	O
+a	O
+minor	O
+role	O
+because	O
+the	O
+strain	O
+did	O
+not	O
+show	O
+distinct	O
+effects	O
+on	O
+the	O
+brain	O
+Hg	O
+concentration	O
+at	O
+PND10	O
+.	O
+
+The	O
+significantly	O
+lower	O
+brain	O
+Hg	O
+concentration	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+compared	O
+with	O
+corresponding	O
+wild	O
+-	O
+type	O
+mice	B
+at	O
+13	O
+weeks	O
+of	O
+age	O
+indicated	O
+that	O
+MT	O
+-	O
+I	O
+,	O
+II	O
+might	O
+play	O
+a	O
+significant	O
+role	O
+in	O
+the	O
+retention	O
+of	O
+Hg	O
+(	O
+or	O
+MeHg	O
+)	O
+.	O
+
+This	O
+is	O
+consistent	O
+with	O
+the	O
+results	O
+of	O
+studies	O
+of	O
+metallic	O
+Hg	O
+exposure	O
+(	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+,	O
+2005	O
+)	O
+;	O
+a	O
+lower	O
+brain	O
+Hg	O
+concentration	O
+may	O
+not	O
+guarantee	O
+lower	O
+toxicity	O
+,	O
+supporting	O
+the	O
+protective	O
+role	O
+of	O
+the	O
+protein	O
+.	O
+
+Earlier	O
+studies	O
+suggest	O
+that	O
+brain	O
+MT	O
+-	O
+I	O
+,	O
+II	O
+has	O
+an	O
+important	O
+role	O
+both	O
+in	O
+the	O
+response	O
+to	O
+oxidative	O
+injury	O
+(	O
+Potter	O
+et	O
+al	O
+.	O
+2007	O
+)	O
+and	O
+in	O
+the	O
+process	O
+of	O
+aging	O
+(	O
+Kojima	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+.	O
+
+Therefore	O
+,	O
+the	O
+lack	O
+of	O
+MT	O
+can	O
+exaggerate	O
+the	O
+toxicity	O
+of	O
+MeHg	O
+by	O
+enhancing	O
+the	O
+initial	O
+effects	O
+due	O
+to	O
+oxygen	O
+radicals	O
+and	O
+/	O
+or	O
+by	O
+accelerating	O
+functional	O
+aging	O
+.	O
+
+Apart	O
+from	O
+this	O
+,	O
+an	O
+intriguing	O
+possibility	O
+is	O
+that	O
+the	O
+brain	O
+-	O
+specific	O
+isoform	O
+,	O
+MT	O
+-	O
+III	O
+,	O
+might	O
+contribute	O
+to	O
+the	O
+results	O
+we	O
+obtained	O
+because	O
+the	O
+expression	O
+of	O
+MT	O
+-	O
+III	O
+,	O
+together	O
+with	O
+MT	O
+-	O
+I	O
+,	O
+is	O
+increased	O
+in	O
+the	O
+brain	O
+of	O
+old	O
+rats	B
+,	O
+resulting	O
+in	O
+the	O
+low	O
+availability	O
+of	O
+free	O
+zinc	O
+for	O
+synapses	O
+(	O
+Mocchegiani	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+The	O
+age	O
+-	O
+dependent	O
+expressions	O
+of	O
+MT	O
+isoforms	O
+might	O
+be	O
+modified	O
+in	O
+MT	O
+-	O
+null	O
+mice	B
+.	O
+
+Results	O
+of	O
+the	O
+present	O
+study	O
+might	O
+allow	O
+the	O
+possibility	O
+of	O
+alternative	O
+interpretations	O
+due	O
+to	O
+some	O
+potentially	O
+confounding	O
+factors	O
+.	O
+
+For	O
+example	O
+,	O
+except	O
+for	O
+the	O
+wild	O
+-	O
+type	O
+females	O
+,	O
+we	O
+observed	O
+significant	O
+differences	O
+in	O
+body	O
+weight	O
+between	O
+MeHg	O
+-	O
+exposed	O
+and	O
+non	O
+-	O
+exposed	O
+groups	O
+.	O
+
+Because	O
+these	O
+differences	O
+only	O
+became	O
+clear	O
+later	O
+in	O
+life	O
+,	O
+they	O
+might	O
+be	O
+associated	O
+with	O
+the	O
+toxicity	O
+that	O
+also	O
+emerged	O
+later	O
+in	O
+life	O
+.	O
+
+Manipulation	O
+of	O
+body	O
+weight	O
+in	O
+rodents	O
+alters	O
+activity	O
+levels	O
+,	O
+although	O
+the	O
+reported	O
+results	O
+are	O
+not	O
+always	O
+consistent	O
+with	O
+each	O
+other	O
+(	O
+Harrison	O
+and	O
+Archer	O
+1987	O
+;	O
+Samuelsson	O
+et	O
+al	O
+.	O
+2008	O
+)	O
+.	O
+
+Also	O
+,	O
+the	O
+differential	O
+performance	O
+in	O
+PA	O
+could	O
+be	O
+related	O
+with	O
+the	O
+potential	O
+effects	O
+of	O
+MeHg	O
+on	O
+(	O
+electric	O
+)	O
+shock	O
+sensitivity	O
+,	O
+which	O
+we	O
+did	O
+not	O
+examine	O
+.	O
+
+At	O
+least	O
+one	O
+high	O
+-	O
+dose	O
+study	O
+with	O
+adult	O
+rats	B
+showed	O
+reduced	O
+electric	O
+sensitivity	O
+due	O
+to	O
+mercury	O
+exposure	O
+(	O
+Wu	O
+et	O
+al	O
+.	O
+1985	O
+)	O
+.	O
+
+These	O
+possibilities	O
+need	O
+to	O
+be	O
+addressed	O
+in	O
+future	O
+studies	O
+.	O
+
+To	O
+summarize	O
+,	O
+the	O
+present	O
+results	O
+suggest	O
+that	O
+an	O
+initial	O
+(	O
+or	O
+triggering	O
+)	O
+toxicologic	O
+event	O
+occurs	O
+before	O
+the	O
+brain	O
+Hg	O
+concentration	O
+stabilizes	O
+and	O
+that	O
+the	O
+nature	O
+of	O
+this	O
+event	O
+should	O
+be	O
+either	O
+an	O
+acceleration	O
+of	O
+the	O
+aging	O
+process	O
+or	O
+interaction	O
+with	O
+the	O
+aging	O
+process	O
+.	O
+
+Thus	O
+,	O
+by	O
+identifying	O
+the	O
+physiologic	O
+events	O
+associated	O
+with	O
+the	O
+functional	O
+aging	O
+of	O
+the	O
+examined	O
+behavioral	O
+tasks	O
+,	O
+the	O
+fundamental	O
+toxicologic	O
+scar	O
+might	O
+be	O
+revealed	O
+.	O
+
+A	O
+Novel	O
+Role	O
+of	O
+the	O
+NRF2	O
+Transcription	O
+Factor	O
+in	O
+the	O
+Regulation	O
+of	O
+Arsenite	O
+-	O
+Mediated	O
+Keratin	O
+16	O
+Gene	O
+Expression	O
+in	O
+Human	B
+Keratinocytes	O
+
+Abstract	O
+
+Background	O
+
+Inorganic	O
+sodium	O
+arsenite	O
+(	O
+iAs	O
+)	O
+is	O
+a	O
+ubiquitous	O
+environmental	O
+contaminant	O
+and	O
+is	O
+associated	O
+with	O
+an	O
+increased	O
+risk	O
+of	O
+skin	O
+hyperkeratosis	O
+and	O
+cancer	O
+.	O
+
+Objectives	O
+
+We	O
+investigated	O
+the	O
+molecular	O
+mechanisms	O
+underlying	O
+the	O
+regulation	O
+of	O
+the	O
+keratin	O
+16	O
+(	O
+K16	O
+)	O
+gene	O
+by	O
+iAs	O
+in	O
+the	O
+human	B
+keratinocyte	O
+cell	O
+line	O
+HaCaT	O
+.	O
+
+Methods	O
+
+We	O
+performed	O
+reverse	O
+transcriptase	O
+polymerase	O
+chain	O
+reaction	O
+,	O
+luciferase	O
+assays	O
+,	O
+Western	O
+blots	O
+,	O
+and	O
+electrophoretic	O
+mobility	O
+shift	O
+assays	O
+to	O
+determine	O
+the	O
+transcriptional	O
+regulation	O
+of	O
+the	O
+K16	O
+gene	O
+by	O
+iAs	O
+.	O
+
+We	O
+used	O
+gene	O
+overexpression	O
+approaches	O
+to	O
+elucidate	O
+the	O
+nuclear	O
+factor	O
+erythroid	O
+-	O
+derived	O
+2	O
+related	O
+factor	O
+2	O
+(	O
+NRF2	O
+)	O
+involved	O
+in	O
+the	O
+K16	O
+induction	O
+.	O
+
+Results	O
+
+iAs	O
+induced	O
+the	O
+mRNA	O
+and	O
+protein	O
+expression	O
+of	O
+K16	O
+.	O
+
+We	O
+also	O
+found	O
+that	O
+the	O
+expression	O
+of	O
+K16	O
+was	O
+transcriptionally	O
+induced	O
+by	O
+iAs	O
+through	O
+activator	O
+protein	O
+-	O
+1	O
+-	O
+like	O
+sites	O
+and	O
+an	O
+antioxidant	O
+response	O
+element	O
+(	O
+ARE	O
+)	O
+in	O
+its	O
+gene	O
+promoter	O
+region	O
+.	O
+
+Treatment	O
+with	O
+iAs	O
+also	O
+enhanced	O
+the	O
+production	O
+and	O
+translocation	O
+of	O
+the	O
+NRF2	O
+transcription	O
+factor	O
+,	O
+an	O
+ARE	O
+-	O
+binding	O
+protein	O
+,	O
+into	O
+the	O
+nucleus	O
+without	O
+modification	O
+of	O
+its	O
+mRNA	O
+expression	O
+.	O
+
+In	O
+addition	O
+,	O
+iAs	O
+elongated	O
+the	O
+half	O
+-	O
+life	O
+of	O
+the	O
+NRF2	O
+protein	O
+.	O
+
+When	O
+overexpressed	O
+in	O
+HaCaT	O
+cells	O
+,	O
+NRF2	O
+was	O
+also	O
+directly	O
+involved	O
+in	O
+not	O
+only	O
+the	O
+up	O
+-	O
+regulation	O
+of	O
+the	O
+detoxification	O
+gene	O
+thioredoxin	O
+but	O
+also	O
+K16	O
+gene	O
+expression	O
+.	O
+
+Conclusions	O
+
+Our	O
+data	O
+clearly	O
+indicate	O
+that	O
+the	O
+K16	O
+gene	O
+is	O
+a	O
+novel	O
+target	O
+of	O
+NRF2	O
+.	O
+
+Furthermore	O
+,	O
+our	O
+findings	O
+also	O
+suggest	O
+that	O
+NRF2	O
+has	O
+opposing	O
+roles	O
+in	O
+the	O
+cell	O
+-	O
+-	O
+in	O
+the	O
+activation	O
+of	O
+detoxification	O
+pathways	O
+and	O
+in	O
+promoting	O
+the	O
+development	O
+of	O
+skin	O
+disorders	O
+.	O
+
+Inorganic	O
+sodium	O
+arsenite	O
+(	O
+iAs	O
+)	O
+,	O
+a	O
+ubiquitous	O
+element	O
+,	O
+is	O
+one	O
+of	O
+the	O
+most	O
+toxic	O
+metals	O
+present	O
+in	O
+the	O
+natural	O
+environment	O
+(	O
+Bagla	O
+and	O
+Kaiser	O
+1996	O
+)	O
+.	O
+
+Arsenicals	O
+are	O
+found	O
+as	O
+naturally	O
+occurring	O
+constituents	O
+of	O
+soil	O
+,	O
+food	O
+,	O
+and	O
+drinking	O
+water	O
+(	O
+Wu	O
+et	O
+al	O
+.	O
+1989	O
+;	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+,	O
+and	O
+exposure	O
+to	O
+iAs	O
+has	O
+been	O
+associated	O
+with	O
+a	O
+variety	O
+of	O
+disease	O
+outcomes	O
+,	O
+including	O
+disorders	O
+of	O
+the	O
+skin	O
+,	O
+urinary	O
+bladder	O
+,	O
+liver	O
+,	O
+and	O
+lung	O
+(	O
+Tchounwou	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+In	O
+particular	O
+,	O
+skin	O
+hyperkeratosis	O
+is	O
+a	O
+characteristic	O
+dermatologic	O
+lesion	O
+associated	O
+with	O
+ingestion	O
+of	O
+arsenic	O
+from	O
+contaminated	O
+groundwater	O
+(	O
+McLellan	O
+2002	O
+;	O
+Yoshida	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+There	O
+is	O
+also	O
+a	O
+significant	O
+association	O
+between	O
+hyperkeratosis	O
+,	O
+nonmelanoma	O
+skin	O
+cancer	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+basal	O
+cell	O
+carcinoma	O
+and	O
+squamous	O
+cell	O
+carcinoma	O
+)	O
+,	O
+and	O
+Bowen	O
+disease	O
+(	O
+Col	O
+et	O
+al	O
+.	O
+1999	O
+;	O
+Rossman	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+pathologic	O
+features	O
+associated	O
+with	O
+arsenic	O
+-	O
+induced	O
+hyperkeratosis	O
+present	O
+as	O
+typical	O
+acanthotic	O
+types	O
+of	O
+psoriasis	O
+-	O
+like	O
+keratosis	O
+,	O
+characterized	O
+by	O
+the	O
+aberrant	O
+proliferation	O
+and	O
+terminal	O
+differentiation	O
+of	O
+epidermal	O
+keratinocytes	O
+(	O
+Lee	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Many	O
+epidemiologic	O
+studies	O
+have	O
+shown	O
+that	O
+hyperkeratoses	O
+are	O
+the	O
+most	O
+frequent	O
+precursor	O
+lesions	O
+of	O
+some	O
+skin	O
+cancers	O
+(	O
+Bagla	O
+and	O
+Kaiser	O
+1996	O
+;	O
+Col	O
+et	O
+al	O
+.	O
+1999	O
+)	O
+.	O
+
+The	O
+keratins	O
+are	O
+the	O
+most	O
+prominent	O
+cytoskeletal	O
+proteins	O
+in	O
+keratinocytes	O
+and	O
+comprise	O
+a	O
+large	O
+family	O
+of	O
+proteins	O
+that	O
+form	O
+intermediate	O
+filament	O
+networks	O
+in	O
+all	O
+epithelial	O
+cell	O
+types	O
+(	O
+Moll	O
+et	O
+al	O
+.	O
+1982	O
+)	O
+.	O
+
+Keratin	O
+16	O
+(	O
+K16	O
+)	O
+and	O
+keratin	O
+6	O
+(	O
+K6	O
+)	O
+genes	O
+are	O
+constitutively	O
+expressed	O
+in	O
+a	O
+number	O
+of	O
+stratified	O
+epithelial	O
+levels	O
+,	O
+including	O
+the	O
+palmar	O
+and	O
+plantar	O
+epidermis	O
+(	O
+Moll	O
+et	O
+al	O
+.	O
+1982	O
+)	O
+.	O
+
+In	O
+skin	O
+diseases	O
+characterized	O
+by	O
+aberrant	O
+proliferation	O
+and	O
+differentiation	O
+,	O
+such	O
+as	O
+psoriasis	O
+and	O
+cancer	O
+,	O
+K16	O
+is	O
+detectable	O
+at	O
+higher	O
+levels	O
+compared	O
+with	O
+normal	O
+tissue	O
+(	O
+Haider	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+tissue	O
+-	O
+specific	O
+overexpression	O
+of	O
+wild	O
+-	O
+type	O
+K16	O
+in	O
+the	O
+epidermis	O
+of	O
+transgenic	O
+mice	B
+results	O
+in	O
+the	O
+hyperproliferation	O
+of	O
+keratinocytes	O
+and	O
+aberrant	O
+keratinization	O
+of	O
+cornified	O
+layers	O
+,	O
+leading	O
+to	O
+hyperkeratosis	O
+of	O
+the	O
+skin	O
+(	O
+Takahashi	O
+et	O
+al	O
+.	O
+1994	O
+)	O
+.	O
+
+Nuclear	O
+factor	O
+erythoid	O
+-	O
+derived	O
+2	O
+related	O
+factor	O
+2	O
+(	O
+NRF2	O
+)	O
+,	O
+a	O
+"	O
+cap	O
+'	O
+n	O
+'	O
+collar	O
+"	O
+basic	O
+leucine	O
+zipper	O
+transcription	O
+factor	O
+,	O
+regulates	O
+a	O
+transcriptional	O
+program	O
+that	O
+maintains	O
+cellular	O
+redox	O
+homeostasis	O
+and	O
+protects	O
+cells	O
+from	O
+oxidative	O
+stress	O
+and	O
+xenobiotic	O
+agents	O
+(	O
+Ishii	O
+et	O
+al	O
+.	O
+2000	O
+;	O
+Moi	O
+et	O
+al	O
+.	O
+1994	O
+)	O
+.	O
+
+Several	O
+detoxifying	O
+and	O
+antioxidant	O
+genes	O
+,	O
+including	O
+glutathione	O
+-	O
+S	O
+-	O
+transferases	O
+(	O
+GSTs	O
+)	O
+,	O
+heme	O
+oxygenase	O
+-	O
+1	O
+(	O
+HMOX1	O
+)	O
+,	O
+and	O
+thioredoxin	O
+(	O
+TXN	O
+)	O
+,	O
+are	O
+regulated	O
+by	O
+NRF2	O
+through	O
+the	O
+antioxidant	O
+responsive	O
+element	O
+(	O
+ARE	O
+)	O
+in	O
+the	O
+respective	O
+promoter	O
+regions	O
+of	O
+these	O
+genes	O
+(	O
+McMahon	O
+et	O
+al	O
+.	O
+2001	O
+;	O
+Wakabayashi	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+NRF2	O
+is	O
+held	O
+in	O
+the	O
+cytoplasm	O
+by	O
+a	O
+cytoskeletal	O
+-	O
+associated	O
+specific	O
+inhibitory	O
+protein	O
+(	O
+kelch	O
+-	O
+like	O
+ECH	O
+-	O
+associated	O
+protein	O
+1	O
+;	O
+KEAP1	O
+)	O
+under	O
+normal	O
+cellular	O
+redox	O
+state	O
+conditions	O
+,	O
+where	O
+it	O
+is	O
+continuously	O
+targeted	O
+by	O
+the	O
+proteasomal	O
+degradation	O
+pathway	O
+(	O
+McMahon	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Upon	O
+exposure	O
+of	O
+the	O
+cell	O
+to	O
+oxidative	O
+stress	O
+or	O
+electrophiles	O
+,	O
+NRF2	O
+can	O
+escape	O
+this	O
+KEAP1	O
+-	O
+mediated	O
+repression	O
+,	O
+translocate	O
+to	O
+the	O
+nucleus	O
+,	O
+and	O
+activate	O
+the	O
+expression	O
+of	O
+its	O
+target	O
+genes	O
+(	O
+Dinkova	O
+-	O
+Kostova	O
+et	O
+al	O
+.	O
+2002	O
+;	O
+McMahon	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Recently	O
+,	O
+studies	O
+of	O
+Keap1	O
+-	O
+/	O
+-	O
+mice	B
+have	O
+shown	O
+that	O
+NRF2	O
+accumulates	O
+in	O
+the	O
+nucleus	O
+and	O
+constitutively	O
+activates	O
+the	O
+transcription	O
+of	O
+its	O
+target	O
+genes	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+stress	O
+signals	O
+(	O
+Wakabayashi	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Most	O
+interestingly	O
+,	O
+however	O
+,	O
+the	O
+skin	O
+,	O
+esophagus	O
+,	O
+and	O
+forestomach	O
+of	O
+Keap1	O
+-	O
+deficient	O
+mice	B
+show	O
+cornified	O
+layer	O
+and	O
+hyperkeratosis	O
+phenotypes	O
+.	O
+
+In	O
+addition	O
+,	O
+previous	O
+studies	O
+have	O
+also	O
+shown	O
+that	O
+the	O
+expression	O
+of	O
+NRF2	O
+and	O
+ARE	O
+-	O
+controlled	O
+genes	O
+is	O
+induced	O
+by	O
+iAs	O
+in	O
+some	O
+cell	O
+types	O
+(	O
+Pi	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Sakurai	O
+et	O
+al	O
+.	O
+2005	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+histochemical	O
+analyses	O
+have	O
+indicated	O
+that	O
+the	O
+expression	O
+of	O
+K16	O
+is	O
+increased	O
+in	O
+Bowen	O
+disease	O
+,	O
+basal	O
+cell	O
+carcinoma	O
+,	O
+and	O
+squamous	O
+cell	O
+carcinoma	O
+induced	O
+by	O
+arsenicals	O
+(	O
+Yu	O
+et	O
+al	O
+.	O
+1993	O
+)	O
+.	O
+
+However	O
+,	O
+it	O
+remains	O
+to	O
+be	O
+determined	O
+whether	O
+NRF2	O
+can	O
+regulate	O
+the	O
+transcriptional	O
+activation	O
+of	O
+K16	O
+upon	O
+iAs	O
+exposure	O
+in	O
+human	B
+keratinocytes	O
+.	O
+
+Hence	O
+,	O
+these	O
+findings	O
+prompted	O
+us	O
+to	O
+investigate	O
+the	O
+molecular	O
+mechanisms	O
+underlying	O
+the	O
+regulation	O
+of	O
+the	O
+K16	O
+gene	O
+by	O
+iAs	O
+-	O
+induced	O
+NRF2	O
+mediation	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Chemicals	O
+and	O
+reagents	O
+
+A	O
+purified	O
+preparation	O
+of	O
+inorganic	O
+sodium	O
+arsenite	O
+(	O
+iAs	O
+;	O
+NaAsO2	O
+;	O
+Merck	O
+,	O
+Darmstadt	O
+,	O
+Germany	O
+)	O
+was	O
+dissolved	O
+in	O
+phosphate	O
+-	O
+buffered	O
+saline	O
+(	O
+PBS	O
+)	O
+and	O
+added	O
+directly	O
+to	O
+the	O
+culture	O
+medium	O
+.	O
+
+A	O
+fresh	O
+iAs	O
+solution	O
+was	O
+prepared	O
+for	O
+each	O
+new	O
+experiment	O
+.	O
+
+Cycloheximide	O
+(	O
+CHX	O
+)	O
+,	O
+dimethyl	O
+-	O
+sulfoxide	O
+(	O
+DMSO	O
+)	O
+,	O
+and	O
+a	O
+protease	O
+inhibitor	O
+cocktail	O
+were	O
+purchased	O
+from	O
+Sigma	O
+(	O
+St	O
+.	O
+Louis	O
+,	O
+MO	O
+,	O
+USA	O
+)	O
+.	O
+
+CHX	O
+was	O
+dissolved	O
+in	O
+DMSO	O
+and	O
+stored	O
+-	O
+20	O
+degrees	O
+C	O
+until	O
+use	O
+.	O
+
+Cells	O
+and	O
+culture	O
+conditions	O
+
+The	O
+human	B
+keratinocyte	O
+HaCaT	O
+cell	O
+line	O
+was	O
+obtained	O
+from	O
+N	O
+.	O
+E	O
+.	O
+
+Fusenig	O
+(	O
+German	O
+Cancer	O
+Research	O
+Center	O
+,	O
+Heidelberg	O
+,	O
+Germany	O
+)	O
+.	O
+
+Cells	O
+were	O
+maintained	O
+in	O
+monolayer	O
+cultures	O
+in	O
+95	O
+%	O
+air	O
+and	O
+5	O
+%	O
+CO2	O
+at	O
+37	O
+degrees	O
+C	O
+in	O
+Dulbecco	O
+'	O
+s	O
+modified	O
+Eagles	O
+medium	O
+(	O
+DMEM	O
+)	O
+supplemented	O
+with	O
+10	O
+%	O
+fetal	O
+bovine	O
+serum	O
+(	O
+FBS	O
+)	O
+,	O
+50	O
+U	O
+/	O
+mL	O
+penicillin	O
+and	O
+50	O
+mg	O
+/	O
+mL	O
+streptomycin	O
+and	O
+nonessential	O
+amino	O
+acids	O
+(	O
+Gibco	O
+BRL	O
+,	O
+Paisley	O
+,	O
+UK	O
+)	O
+.	O
+
+RNA	O
+preparation	O
+and	O
+semiquantitative	O
+reverse	O
+transcriptase	O
+-	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+RT	O
+-	O
+PCR	O
+)	O
+analysis	O
+
+We	O
+determined	O
+RNA	O
+expression	O
+levels	O
+by	O
+semiquantitative	O
+RT	O
+-	O
+PCR	O
+analysis	O
+as	O
+described	O
+previously	O
+(	O
+Sugioka	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Total	O
+RNA	O
+was	O
+isolated	O
+from	O
+HaCaT	O
+cells	O
+using	O
+the	O
+GeneElute	O
+Mammalian	O
+Total	O
+RNA	O
+Kit	O
+(	O
+Sigma	O
+)	O
+.	O
+
+The	O
+specific	O
+primers	O
+used	O
+for	O
+first	O
+-	O
+strand	O
+cDNA	O
+synthesis	O
+and	O
+PCR	O
+were	O
+as	O
+follows	O
+:	O
+K16	O
+[	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+GAT	O
+GCT	O
+TGC	O
+TCT	O
+GAG	O
+AGG	O
+TC	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+CCA	O
+GCA	O
+AGA	O
+TCT	O
+GGT	O
+ACT	O
+CC	O
+-	O
+3	O
+'	O
+;	O
+Gene	O
+Bank	O
+accession	O
+no	O
+.	O
+NM	O
+_	O
+005557	O
+(	O
+National	O
+Center	O
+for	O
+Biotechnology	O
+Information	O
+2007	O
+)	O
+]	O
+;	O
+c	O
+-	O
+Jun	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+CCT	O
+GTT	O
+GCG	O
+GCC	O
+CCG	O
+AAA	O
+CT	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+ACC	O
+ATG	O
+CCT	O
+GCC	O
+CCG	O
+TTG	O
+AC	O
+-	O
+3	O
+'	O
+;	O
+NM	O
+_	O
+002228	O
+)	O
+;	O
+c	O
+-	O
+Fos	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+TTT	O
+GCC	O
+TAA	O
+CCG	O
+CCA	O
+CGA	O
+TGA	O
+T	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+TTG	O
+CCG	O
+CTT	O
+TCT	O
+GCC	O
+ACC	O
+TC	O
+-	O
+3	O
+'	O
+;	O
+NM	O
+_	O
+005252	O
+)	O
+;	O
+NRF2	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+AGA	O
+TTC	O
+ACA	O
+GGC	O
+CTT	O
+TCT	O
+CG	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+CAG	O
+CTC	O
+TCC	O
+CTA	O
+CCG	O
+TTG	O
+GA	O
+-	O
+3	O
+'	O
+;	O
+AF323119	O
+)	O
+;	O
+KEAP1	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+CAG	O
+AGG	O
+TGG	O
+TGG	O
+TGT	O
+TGC	O
+TTA	O
+T	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+AGC	O
+TCG	O
+TTC	O
+ATG	O
+ATG	O
+CCA	O
+AAG	O
+-	O
+3	O
+'	O
+;	O
+NM	O
+_	O
+012289	O
+)	O
+;	O
+TXN	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+CAG	O
+GGG	O
+AAT	O
+GAA	O
+AGA	O
+AAG	O
+G	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+CAA	O
+GGT	O
+GAA	O
+GCA	O
+GAT	O
+CG	O
+-	O
+3	O
+'	O
+;	O
+NM	O
+_	O
+003329	O
+)	O
+,	O
+and	O
+glyceraldehyde	O
+3	O
+-	O
+phosphate	O
+dehydrogenase	O
+(	O
+GAPDH	O
+)	O
+as	O
+a	O
+loading	O
+control	O
+(	O
+forward	O
+,	O
+5	O
+'	O
+-	O
+ACC	O
+ACA	O
+GTC	O
+CAT	O
+GCC	O
+ATC	O
+AC	O
+-	O
+3	O
+'	O
+,	O
+and	O
+reverse	O
+,	O
+5	O
+'	O
+-	O
+TCC	O
+ACC	O
+ACC	O
+CTG	O
+TTG	O
+CTG	O
+TA	O
+-	O
+3	O
+'	O
+,	O
+NM	O
+_	O
+002046	O
+)	O
+.	O
+
+PCR	O
+products	O
+were	O
+separated	O
+on	O
+a	O
+1	O
+.	O
+8	O
+%	O
+agarose	O
+gel	O
+and	O
+stained	O
+with	O
+ethidium	O
+bromide	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+
+We	O
+performed	O
+Western	O
+blot	O
+analysis	O
+as	O
+described	O
+previously	O
+(	O
+Sugioka	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+Briefly	O
+,	O
+nuclear	O
+and	O
+cytoplasmic	O
+proteins	O
+were	O
+extracted	O
+using	O
+the	O
+NE	O
+-	O
+PER	O
+nuclear	O
+and	O
+cytoplasmic	O
+extraction	O
+kit	O
+(	O
+Pierce	O
+,	O
+Rockford	O
+,	O
+IL	O
+,	O
+USA	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+For	O
+protein	O
+extraction	O
+,	O
+the	O
+cells	O
+were	O
+lysed	O
+in	O
+a	O
+buffer	O
+containing	O
+complete	O
+protease	O
+inhibitor	O
+cocktail	O
+.	O
+
+We	O
+measured	O
+protein	O
+concentrations	O
+using	O
+the	O
+DC	O
+Protein	O
+Assay	O
+Kit	O
+(	O
+Bio	O
+-	O
+Rad	O
+,	O
+Richmond	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+Equal	O
+amounts	O
+of	O
+protein	O
+were	O
+then	O
+resolved	O
+by	O
+sodium	O
+dodecyl	O
+sulfate	O
+-	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+(	O
+SDS	O
+-	O
+PAGE	O
+)	O
+and	O
+transferred	O
+to	O
+a	O
+polyvinylidene	O
+fluoride	O
+membrane	O
+(	O
+Amersham	O
+Biosciences	O
+,	O
+Bucks	O
+,	O
+UK	O
+)	O
+.	O
+
+Immunoblotting	O
+was	O
+carried	O
+out	O
+with	O
+specific	O
+antibodies	O
+in	O
+Tris	O
+-	O
+buffered	O
+saline	O
+with	O
+0	O
+.	O
+05	O
+%	O
+Tween	O
+20	O
+.	O
+
+The	O
+primary	O
+antibodies	O
+were	O
+as	O
+follows	O
+:	O
+K16	O
+(	O
+Neomarkers	O
+,	O
+Fremont	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+,	O
+NRF2	O
+and	O
+KEAP1	O
+(	O
+Santa	O
+Cruz	O
+Biotechnology	O
+,	O
+Santa	O
+Cruz	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+,	O
+c	O
+-	O
+Jun	O
+(	O
+Cell	O
+Signaling	O
+,	O
+Beverly	O
+,	O
+MA	O
+,	O
+USA	O
+)	O
+,	O
+and	O
+beta	O
+-	O
+actin	O
+(	O
+Sigma	O
+)	O
+.	O
+
+After	O
+washing	O
+,	O
+the	O
+membranes	O
+were	O
+probed	O
+with	O
+horseradish	B
+peroxidase	O
+-	O
+conjugated	O
+secondary	O
+antibodies	O
+and	O
+developed	O
+by	O
+chemiluminescence	O
+using	O
+the	O
+ECL	O
+Plus	O
+Detection	O
+Kit	O
+(	O
+Amersham	O
+Biosciences	O
+)	O
+.	O
+
+Plasmids	O
+,	O
+transfections	O
+,	O
+and	O
+luciferase	O
+assays	O
+
+Human	B
+K16	O
+promoter	O
+regions	O
+of	O
+varying	O
+lengths	O
+(	O
+pXK	O
+-	O
+1	O
+,	O
+3	O
+,	O
+4	O
+,	O
+5	O
+-	O
+1	O
+,	O
+and	O
+5	O
+-	O
+2	O
+)	O
+were	O
+provided	O
+by	O
+Y	O
+-	O
+N	O
+Wang	O
+(	O
+National	O
+Cheng	O
+Kung	O
+University	O
+,	O
+Taiwan	O
+)	O
+.	O
+
+These	O
+DNA	O
+fragments	O
+were	O
+prepared	O
+from	O
+HaCaT	O
+cells	O
+and	O
+were	O
+ligated	O
+into	O
+the	O
+pXP	O
+-	O
+1	O
+luciferase	O
+vector	O
+(	O
+Wang	O
+and	O
+Chang	O
+2003	O
+)	O
+.	O
+
+The	O
+p3xARE	O
+/	O
+Luc	O
+vector	O
+,	O
+harboring	O
+three	O
+tandem	O
+repeats	O
+of	O
+ARE	O
+,	O
+was	O
+donated	O
+by	O
+X	O
+.	O
+L	O
+.	O
+
+Chen	O
+(	O
+Discovery	O
+Research	O
+,	O
+AtheroGenics	O
+Inc	O
+.	O
+,	O
+Alpharetta	O
+,	O
+GA	O
+,	O
+USA	O
+)	O
+(	O
+Chen	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+The	O
+wild	O
+-	O
+type	O
+NRF2	O
+expression	O
+vector	O
+(	O
+WT	O
+-	O
+NRF2	O
+)	O
+was	O
+a	O
+gift	O
+from	O
+H	O
+.	O
+S	O
+.	O
+
+So	O
+(	O
+Wonkwang	O
+University	O
+School	O
+of	O
+Medicine	O
+,	O
+Korea	O
+)	O
+(	O
+So	O
+et	O
+al	O
+.	O
+2006	O
+)	O
+.	O
+
+NRF2	O
+cDNA	O
+was	O
+subcloned	O
+into	O
+a	O
+pcDNA3	O
+.	O
+1	O
+(	O
++	O
+)	O
+vector	O
+(	O
+Invitrogen	O
+,	O
+San	O
+Diego	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+For	O
+the	O
+transfection	O
+of	O
+reporter	O
+plasmids	O
+,	O
+we	O
+seeded	O
+HaCaT	O
+cells	O
+into	O
+six	O
+-	O
+well	O
+plates	O
+at	O
+a	O
+density	O
+of	O
+80	O
+%	O
+the	O
+previous	O
+day	O
+.	O
+
+Cells	O
+were	O
+then	O
+transfected	O
+with	O
+a	O
+total	O
+of	O
+each	O
+luciferase	O
+reporter	O
+construct	O
+(	O
+2	O
+.	O
+5	O
+mu	O
+g	O
+)	O
+using	O
+LipofectAMINE	O
+plus	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+To	O
+control	O
+for	O
+the	O
+efficiency	O
+of	O
+transfection	O
+,	O
+Renilla	O
+luciferase	O
+gene	O
+expression	O
+was	O
+monitored	O
+using	O
+either	O
+the	O
+pRL	O
+-	O
+CMV	O
+or	O
+pRL	O
+-	O
+TK	O
+vectors	O
+(	O
+Promega	O
+,	O
+Madison	O
+,	O
+WI	O
+,	O
+USA	O
+)	O
+.	O
+
+For	O
+overexpression	O
+of	O
+WT	O
+-	O
+NRF2	O
+,	O
+we	O
+normalized	O
+the	O
+total	O
+plasmid	O
+concentration	O
+using	O
+the	O
+pcDNA3	O
+.	O
+1	O
+(	O
++	O
+)	O
+empty	O
+vector	O
+.	O
+
+Thirty	O
+-	O
+six	O
+hours	O
+after	O
+transfection	O
+,	O
+the	O
+medium	O
+was	O
+replaced	O
+with	O
+fresh	O
+medium	O
+containing	O
+either	O
+vehicle	O
+(	O
+PBS	O
+)	O
+or	O
+iAs	O
+for	O
+6	O
+hr	O
+.	O
+
+After	O
+iAs	O
+exposure	O
+,	O
+we	O
+harvested	O
+cells	O
+and	O
+analyzed	O
+them	O
+for	O
+luciferase	O
+activity	O
+using	O
+a	O
+Dual	O
+-	O
+Luciferase	O
+Reporter	O
+Assay	O
+System	O
+(	O
+Promega	O
+)	O
+.	O
+
+For	O
+the	O
+investigation	O
+of	O
+the	O
+role	O
+of	O
+NRF2	O
+in	O
+regulating	O
+K16	O
+gene	O
+expression	O
+,	O
+transfection	O
+of	O
+an	O
+NRF2	O
+expression	O
+plasmid	O
+into	O
+HaCaT	O
+cells	O
+was	O
+carried	O
+out	O
+using	O
+LipofectAMINE	O
+2000	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+Cells	O
+were	O
+cultured	O
+in	O
+100	O
+-	O
+mm	O
+plates	O
+24	O
+hr	O
+before	O
+transfection	O
+.	O
+
+The	O
+expression	O
+plasmid	O
+WT	O
+-	O
+NRF2	O
+(	O
+15	O
+mu	O
+g	O
+)	O
+was	O
+then	O
+transfected	O
+into	O
+the	O
+cells	O
+for	O
+48	O
+-	O
+60	O
+hr	O
+.	O
+
+As	O
+a	O
+negative	O
+control	O
+,	O
+we	O
+used	O
+15	O
+mu	O
+g	O
+of	O
+the	O
+pcDNA3	O
+.	O
+1	O
+(	O
++	O
+)	O
+empty	O
+vector	O
+.	O
+
+Electrophoretic	O
+mobility	O
+-	O
+shift	O
+assays	O
+(	O
+EMSA	O
+)	O
+
+We	O
+extracted	O
+and	O
+measured	O
+nuclear	O
+proteins	O
+as	O
+described	O
+above	O
+.	O
+
+Nuclear	O
+protein	O
+/	O
+DNA	O
+complexes	O
+were	O
+subjected	O
+to	O
+electrophoresis	O
+in	O
+nondenaturing	O
+5	O
+%	O
+polyacrylamide	O
+gels	O
+containing	O
+2	O
+%	O
+glycerol	O
+in	O
+0	O
+.	O
+25	O
+%	O
+Tris	O
+-	O
+borate	O
+/	O
+EDTA	O
+buffer	O
+and	O
+transferred	O
+to	O
+Hybond	O
+-	O
+N	O
++	O
+nylon	O
+transfer	O
+membranes	O
+(	O
+Amersham	O
+Biosciences	O
+)	O
+for	O
+detection	O
+using	O
+the	O
+Light	O
+-	O
+Shift	O
+EMSA	O
+kit	O
+(	O
+Pierce	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+,	O
+with	O
+minor	O
+modifications	O
+.	O
+
+We	O
+incubated	O
+10	O
+-	O
+mu	O
+g	O
+aliquots	O
+of	O
+nuclear	O
+extract	O
+with	O
+the	O
+DNA	O
+probe	O
+in	O
+a	O
+binding	O
+reaction	O
+buffer	O
+containing	O
+10	O
+mM	O
+Tris	O
+/	O
+HCl	O
+(	O
+pH	O
+7	O
+.	O
+6	O
+)	O
+,	O
+50	O
+mM	O
+KCl	O
+,	O
+0	O
+.	O
+5	O
+mM	O
+dithiothreitol	O
+,	O
+0	O
+.	O
+25	O
+mM	O
+EDTA	O
+,	O
+5	O
+%	O
+glycerol	O
+,	O
+2	O
+.	O
+5	O
+mM	O
+MgCl2	O
+,	O
+0	O
+.	O
+05	O
+%	O
+NP	O
+-	O
+40	O
+detergent	O
+,	O
+and	O
+2	O
+mu	O
+g	O
+of	O
+poly	O
+(	O
+dI	O
+-	O
+dC	O
+)	O
+.	O
+poly	O
+(	O
+dI	O
+-	O
+dC	O
+)	O
+for	O
+30	O
+min	O
+at	O
+room	O
+temperature	O
+.	O
+
+For	O
+supershift	O
+assays	O
+,	O
+2	O
+mu	O
+g	O
+of	O
+either	O
+a	O
+polyclonal	O
+anti	O
+-	O
+NRF2	O
+or	O
+an	O
+anti	O
+-	O
+c	O
+-	O
+Jun	O
+antibody	O
+(	O
+Santa	O
+Cruz	O
+Biotechnology	O
+)	O
+was	O
+added	O
+with	O
+the	O
+nuclear	O
+protein	O
+for	O
+2	O
+hr	O
+at	O
+4	O
+degrees	O
+C	O
+before	O
+the	O
+labeled	O
+oligonucleotide	O
+probe	O
+was	O
+added	O
+.	O
+
+Biotin	O
+-	O
+labeled	O
+,	O
+double	O
+-	O
+stranded	O
+oligonucleotides	O
+WT	O
+-	O
+K16ARE	O
+(	O
+-	O
+157	O
+/	O
+-	O
+132	O
+,	O
+5	O
+'	O
+-	O
+GGGGAACCTGGAGTCAGCAG	O
+-	O
+TAGGA	O
+-	O
+3	O
+'	O
+)	O
+,	O
+containing	O
+an	O
+ARE	O
+site	O
+(	O
+-	O
+148	O
+/	O
+-	O
+140	O
+,	O
+underlined	O
+)	O
+in	O
+the	O
+human	B
+K16	O
+promoter	O
+region	O
+,	O
+and	O
+Mut	O
+-	O
+K16ARE	O
+(	O
+5	O
+'	O
+-	O
+GGGGAA	O
+-	O
+CCTGGAGTCAaaAGTTAGGA	O
+-	O
+3	O
+'	O
+,	O
+mutated	O
+GC	O
+box	O
+in	O
+the	O
+ARE	O
+)	O
+were	O
+prepared	O
+by	O
+Fasmac	O
+(	O
+Kanagawa	O
+,	O
+Japan	O
+)	O
+.	O
+
+A	O
+consensus	O
+ARE	O
+probe	O
+was	O
+purchased	O
+from	O
+Panomics	O
+,	O
+Inc	O
+.	O
+
+(	O
+Redwood	O
+City	O
+,	O
+CA	O
+,	O
+USA	O
+)	O
+.	O
+
+For	O
+competition	O
+binding	O
+of	O
+the	O
+K16	O
+ARE	O
+-	O
+complexes	O
+,	O
+we	O
+used	O
+an	O
+unlabeled	O
+AP	O
+-	O
+1	O
+consensus	O
+oligonucleotide	O
+(	O
+5	O
+'	O
+-	O
+TATC	O
+-	O
+GATAAGCTATGAGTCATCCG	O
+-	O
+3	O
+'	O
+)	O
+.	O
+
+The	O
+binding	O
+specificity	O
+was	O
+confirmed	O
+in	O
+each	O
+case	O
+by	O
+the	O
+addition	O
+of	O
+a	O
+100	O
+-	O
+fold	O
+molar	O
+excess	O
+of	O
+unlabeled	O
+oligonucleotide	O
+.	O
+
+CHX	O
+chase	O
+experiment	O
+
+We	O
+investigated	O
+the	O
+posttranscriptional	O
+regulation	O
+of	O
+both	O
+the	O
+steady	O
+-	O
+state	O
+levels	O
+and	O
+half	O
+-	O
+life	O
+of	O
+the	O
+NRF2	O
+protein	O
+by	O
+CHX	O
+chase	O
+analysis	O
+.	O
+
+Cells	O
+were	O
+incubated	O
+in	O
+serum	O
+-	O
+free	O
+medium	O
+in	O
+the	O
+absence	O
+or	O
+presence	O
+of	O
+iAs	O
+for	O
+6	O
+hr	O
+.	O
+
+The	O
+culture	O
+medium	O
+was	O
+then	O
+replaced	O
+with	O
+serum	O
+-	O
+free	O
+medium	O
+containing	O
+CHX	O
+(	O
+100	O
+mu	O
+g	O
+/	O
+mL	O
+)	O
+.	O
+
+We	O
+prepared	O
+cell	O
+lysates	O
+at	O
+0	O
+,	O
+10	O
+,	O
+30	O
+,	O
+60	O
+,	O
+120	O
+,	O
+and	O
+240	O
+min	O
+after	O
+iAs	O
+treatment	O
+.	O
+
+Whole	O
+-	O
+cell	O
+lysates	O
+were	O
+resolved	O
+by	O
+SDS	O
+-	O
+PAGE	O
+and	O
+immunoblotted	O
+with	O
+antibodies	O
+against	O
+NRF2	O
+.	O
+
+Statistics	O
+
+All	O
+the	O
+data	O
+generated	O
+from	O
+at	O
+least	O
+three	O
+independent	O
+experiments	O
+and	O
+expressed	O
+as	O
+the	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+were	O
+analyzed	O
+by	O
+the	O
+Student	O
+'	O
+s	O
+t	O
+-	O
+test	O
+.	O
+
+Statistical	O
+comparisons	O
+were	O
+made	O
+by	O
+logarithmic	O
+transformation	O
+of	O
+the	O
+normalized	O
+values	O
+.	O
+
+We	O
+considered	O
+p	O
+-	O
+values	O
+<	O
+0	O
+.	O
+01	O
+to	O
+be	O
+statistically	O
+significant	O
+.	O
+
+Results	O
+
+K16	O
+expression	O
+is	O
+induced	O
+by	O
+iAs	O
+in	O
+HaCaT	O
+cells	O
+
+We	O
+wanted	O
+to	O
+determine	O
+whether	O
+the	O
+K16	O
+mRNA	O
+is	O
+transcriptionally	O
+regulated	O
+by	O
+iAs	O
+,	O
+and	O
+treated	O
+HaCaT	O
+cells	O
+with	O
+this	O
+compound	O
+for	O
+various	O
+time	O
+periods	O
+over	O
+a	O
+range	O
+of	O
+doses	O
+.	O
+
+After	O
+treatment	O
+of	O
+HaCaT	O
+cells	O
+with	O
+1	O
+-	O
+20	O
+mu	O
+M	O
+iAs	O
+,	O
+the	O
+expression	O
+of	O
+K16	O
+mRNA	O
+was	O
+increased	O
+compared	O
+with	O
+the	O
+control	O
+at	O
+6	O
+hr	O
+(	O
+Figure	O
+1A	O
+)	O
+but	O
+had	O
+declined	O
+to	O
+basal	O
+levels	O
+at	O
+24	O
+hr	O
+.	O
+
+The	O
+increase	O
+in	O
+the	O
+K16	O
+protein	O
+levels	O
+after	O
+6	O
+hr	O
+of	O
+iAs	O
+exposure	O
+was	O
+just	O
+detectable	O
+at	O
+10	O
+-	O
+20	O
+mu	O
+M	O
+,	O
+but	O
+a	O
+dose	O
+-	O
+dependent	O
+increase	O
+was	O
+more	O
+evident	O
+at	O
+10	O
+hr	O
+(	O
+Figure	O
+1B	O
+)	O
+.	O
+
+This	O
+enhancement	O
+of	O
+K16	O
+expression	O
+had	O
+declined	O
+to	O
+basal	O
+levels	O
+at	O
+24	O
+hr	O
+.	O
+
+Identification	O
+of	O
+the	O
+iAs	O
+responsive	O
+region	O
+in	O
+the	O
+K16	O
+gene	O
+promoter	O
+
+To	O
+investigate	O
+the	O
+mechanisms	O
+underlying	O
+the	O
+transactivation	O
+of	O
+the	O
+K16	O
+gene	O
+by	O
+iAs	O
+,	O
+we	O
+first	O
+examined	O
+the	O
+response	O
+of	O
+the	O
+K16	O
+regulatory	O
+region	O
+to	O
+this	O
+compound	O
+using	O
+a	O
+luciferase	O
+reporter	O
+gene	O
+assay	O
+.	O
+
+The	O
+dose	O
+-	O
+dependent	O
+activation	O
+of	O
+K16	O
+transcription	O
+after	O
+iAs	O
+treatment	O
+was	O
+observed	O
+with	O
+a	O
+construct	O
+containing	O
+a	O
+515	O
+-	O
+bp	O
+fragment	O
+of	O
+the	O
+K16	O
+promoter	O
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+To	O
+further	O
+elucidate	O
+the	O
+region	O
+containing	O
+the	O
+iAs	O
+responsive	O
+element	O
+,	O
+we	O
+examined	O
+a	O
+series	O
+of	O
+deletions	O
+of	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+K16	O
+gene	O
+.	O
+
+The	O
+ARE	O
+sequence	O
+in	O
+the	O
+pXK	O
+-	O
+5	O
+-	O
+1	O
+vector	O
+contains	O
+an	O
+activator	O
+protein	O
+-	O
+1	O
+(	O
+AP	O
+-	O
+1	O
+)	O
+-	O
+like	O
+element	O
+followed	O
+by	O
+a	O
+GC	O
+box	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+2B	O
+,	O
+an	O
+enhancement	O
+in	O
+the	O
+reporter	O
+activity	O
+levels	O
+was	O
+observed	O
+for	O
+the	O
+promoter	O
+constructs	O
+,	O
+pXK	O
+-	O
+1	O
+,	O
+3	O
+,	O
+4	O
+,	O
+and	O
+5	O
+-	O
+1	O
+,	O
+in	O
+response	O
+to	O
+20	O
+mu	O
+M	O
+iAs	O
+.	O
+
+A	O
+decline	O
+in	O
+reporter	O
+activity	O
+,	O
+however	O
+,	O
+depended	O
+on	O
+the	O
+number	O
+of	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+sites	O
+,	O
+and	O
+the	O
+results	O
+for	O
+the	O
+pXK	O
+-	O
+5	O
+-	O
+1	O
+construct	O
+show	O
+also	O
+that	O
+ARE	O
+is	O
+activated	O
+by	O
+iAs	O
+.	O
+
+In	O
+contrast	O
+,	O
+no	O
+significant	O
+activation	O
+was	O
+observed	O
+using	O
+a	O
+pXK	O
+-	O
+5	O
+-	O
+2	O
+construct	O
+in	O
+response	O
+to	O
+20	O
+mu	O
+M	O
+iAs	O
+.	O
+
+Expression	O
+of	O
+AP	O
+-	O
+1	O
+transcriptions	O
+factor	O
+and	O
+c	O
+-	O
+Jun	O
+production	O
+following	O
+iAs	O
+treatment	O
+
+We	O
+examined	O
+AP	O
+-	O
+1	O
+transcription	O
+factors	O
+c	O
+-	O
+Jun	O
+and	O
+c	O
+-	O
+Fos	O
+expression	O
+in	O
+iAs	O
+-	O
+treated	O
+HaCaT	O
+cells	O
+by	O
+semiquantitative	O
+RT	O
+-	O
+PCR	O
+.	O
+
+iAs	O
+-	O
+induced	O
+c	O
+-	O
+Jun	O
+expression	O
+was	O
+observed	O
+during	O
+the	O
+first	O
+3	O
+hr	O
+after	O
+treatment	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+An	O
+appreciable	O
+induction	O
+of	O
+c	O
+-	O
+Jun	O
+was	O
+also	O
+confirmed	O
+after	O
+6	O
+hr	O
+,	O
+but	O
+this	O
+was	O
+down	O
+-	O
+regulated	O
+by	O
+24	O
+hr	O
+after	O
+iAs	O
+treatment	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+expression	O
+of	O
+c	O
+-	O
+Fos	O
+was	O
+only	O
+transiently	O
+detectable	O
+at	O
+3	O
+hr	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+but	O
+was	O
+not	O
+observed	O
+during	O
+the	O
+6	O
+-	O
+24	O
+hr	O
+period	O
+of	O
+this	O
+experiment	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+3B	O
+,	O
+iAs	O
+-	O
+enhanced	O
+c	O
+-	O
+Jun	O
+production	O
+can	O
+be	O
+observed	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+at	O
+6	O
+hr	O
+,	O
+but	O
+it	O
+declines	O
+from	O
+10	O
+to	O
+24	O
+hr	O
+.	O
+
+iAs	O
+potently	O
+induces	O
+the	O
+translocation	O
+of	O
+NRF2	O
+and	O
+activates	O
+the	O
+ARE	O
+of	O
+the	O
+K16	O
+promoter	O
+
+The	O
+results	O
+of	O
+our	O
+reporter	O
+assays	O
+suggested	O
+that	O
+iAs	O
+stimulates	O
+not	O
+only	O
+the	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+sites	O
+but	O
+also	O
+the	O
+ARE	O
+site	O
+within	O
+the	O
+K16	O
+gene	O
+promoter	O
+in	O
+HaCaT	O
+cells	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+several	O
+oxidative	O
+stress	O
+agents	O
+and	O
+toxic	O
+chemicals	O
+,	O
+including	O
+iAs	O
+,	O
+have	O
+been	O
+reported	O
+to	O
+induce	O
+the	O
+expression	O
+of	O
+ARE	O
+-	O
+dependent	O
+genes	O
+in	O
+several	O
+cell	O
+types	O
+(	O
+Pi	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Sakurai	O
+et	O
+al	O
+.	O
+2005	O
+)	O
+.	O
+
+On	O
+the	O
+basis	O
+of	O
+our	O
+observations	O
+and	O
+some	O
+recent	O
+reports	O
+,	O
+we	O
+thus	O
+hypothesized	O
+that	O
+iAs	O
+would	O
+have	O
+the	O
+ability	O
+to	O
+activate	O
+the	O
+ARE	O
+of	O
+the	O
+K16	O
+gene	O
+promoter	O
+directly	O
+,	O
+resulting	O
+in	O
+the	O
+induction	O
+of	O
+K16	O
+expression	O
+in	O
+HaCaT	O
+cells	O
+.	O
+
+To	O
+confirm	O
+that	O
+the	O
+K16	O
+ARE	O
+indeed	O
+functions	O
+as	O
+an	O
+iAs	O
+-	O
+responsive	O
+transcriptional	O
+control	O
+element	O
+,	O
+we	O
+performed	O
+transient	O
+transfections	O
+of	O
+HaCaT	O
+cells	O
+with	O
+a	O
+p3xARE	O
+/	O
+Luc	O
+construct	O
+and	O
+then	O
+subjected	O
+these	O
+cells	O
+to	O
+iAs	O
+for	O
+6	O
+hr	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+4A	O
+,	O
+treatment	O
+of	O
+HaCaT	O
+cells	O
+with	O
+iAs	O
+results	O
+in	O
+a	O
+dramatic	O
+increase	O
+in	O
+ARE	O
+-	O
+driven	O
+promoter	O
+activity	O
+.	O
+
+Likewise	O
+,	O
+EMSA	O
+using	O
+a	O
+consensus	O
+ARE	O
+probe	O
+show	O
+that	O
+iAs	O
+-	O
+induced	O
+ARE	O
+-	O
+binding	O
+complexes	O
+increase	O
+markedly	O
+,	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+fashion	O
+(	O
+Figure	O
+4B	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+iAs	O
+has	O
+the	O
+ability	O
+to	O
+activate	O
+the	O
+ARE	O
+-	O
+driven	O
+genes	O
+.	O
+
+We	O
+performed	O
+further	O
+EMSA	O
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+using	O
+an	O
+ARE	O
+probe	O
+specific	O
+to	O
+the	O
+K16	O
+proximal	O
+promoter	O
+region	O
+(	O
+WT	O
+-	O
+K16ARE	O
+)	O
+and	O
+found	O
+that	O
+K16ARE	O
+-	O
+nuclear	O
+protein	O
+complexes	O
+formation	O
+is	O
+augmented	O
+by	O
+iAs	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+(	O
+Figure	O
+4C	O
+)	O
+.	O
+
+Moreover	O
+,	O
+the	O
+formation	O
+of	O
+these	O
+complexes	O
+is	O
+specifically	O
+inhibited	O
+by	O
+the	O
+addition	O
+of	O
+excess	O
+unlabeled	O
+oligonucleotide	O
+competitor	O
+(	O
+Figure	O
+4B	O
+,	O
+C	O
+)	O
+,	O
+whereas	O
+an	O
+excess	O
+of	O
+an	O
+unlabeled	O
+AP	O
+-	O
+1	O
+probe	O
+competes	O
+only	O
+marginally	O
+for	O
+K16ARE	O
+binding	O
+(	O
+Figure	O
+4C	O
+)	O
+.	O
+
+The	O
+NRF2	O
+transcription	O
+factor	O
+has	O
+been	O
+shown	O
+to	O
+bind	O
+to	O
+AREs	O
+upon	O
+translocation	O
+into	O
+the	O
+nucleus	O
+,	O
+resulting	O
+in	O
+the	O
+induction	O
+of	O
+ARE	O
+-	O
+mediated	O
+genes	O
+(	O
+Wakabayashi	O
+et	O
+al	O
+.	O
+2004	O
+)	O
+.	O
+
+To	O
+examine	O
+whether	O
+iAs	O
+induces	O
+and	O
+translocates	O
+NRF2	O
+into	O
+the	O
+nucleus	O
+in	O
+HaCaT	O
+cells	O
+,	O
+we	O
+treated	O
+these	O
+cells	O
+with	O
+iAs	O
+for	O
+either	O
+3	O
+or	O
+6	O
+hr	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+4D	O
+,	O
+a	O
+dose	O
+-	O
+dependent	O
+accumulation	O
+of	O
+NRF2	O
+protein	O
+was	O
+observed	O
+in	O
+the	O
+nucleus	O
+upon	O
+treatment	O
+with	O
+iAs	O
+for	O
+6	O
+hr	O
+.	O
+
+This	O
+was	O
+not	O
+observed	O
+in	O
+the	O
+parallel	O
+experiment	O
+performed	O
+over	O
+the	O
+3	O
+-	O
+hr	O
+time	O
+course	O
+.	O
+
+Supershift	O
+EMSA	O
+analysis	O
+using	O
+an	O
+NRF2	O
+antibody	O
+showed	O
+that	O
+the	O
+iAs	O
+-	O
+induced	O
+and	O
+iAs	O
+-	O
+translocated	O
+NRF2	O
+protein	O
+binds	O
+to	O
+the	O
+WT	O
+-	O
+K16ARE	O
+probe	O
+containing	O
+the	O
+ARE	O
+sequence	O
+of	O
+the	O
+K16	O
+proximal	O
+promoter	O
+region	O
+(	O
+5	O
+'	O
+-	O
+GGAGTCAGC	O
+-	O
+3	O
+'	O
+)	O
+that	O
+comprises	O
+an	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+site	O
+and	O
+a	O
+GC	O
+box	O
+,	O
+whereas	O
+the	O
+supershift	O
+of	O
+c	O
+-	O
+Jun	O
+was	O
+not	O
+observed	O
+(	O
+Figure	O
+4E	O
+)	O
+.	O
+
+To	O
+identify	O
+whether	O
+the	O
+GC	O
+box	O
+is	O
+dispensable	O
+for	O
+the	O
+iAs	O
+-	O
+stimulated	O
+binding	O
+activity	O
+of	O
+NRF2	O
+,	O
+we	O
+next	O
+performed	O
+EMSA	O
+analyses	O
+with	O
+either	O
+WT	O
+-	O
+or	O
+a	O
+Mut	O
+-	O
+K16ARE	O
+probe	O
+containing	O
+an	O
+intact	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+element	O
+but	O
+a	O
+mutated	O
+GC	O
+box	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+4F	O
+,	O
+the	O
+K16ARE	O
+-	O
+nuclear	O
+protein	O
+complexes	O
+and	O
+supershifted	O
+bands	O
+that	O
+were	O
+enhanced	O
+by	O
+iAs	O
+treatment	O
+were	O
+largely	O
+abolished	O
+by	O
+the	O
+addition	O
+of	O
+the	O
+Mut	O
+-	O
+K16ARE	O
+probe	O
+.	O
+
+iAs	O
+stabilizes	O
+the	O
+NRF2	O
+protein	O
+
+We	O
+examined	O
+the	O
+effects	O
+of	O
+iAs	O
+treatment	O
+on	O
+the	O
+function	O
+of	O
+KEAP1	O
+in	O
+HaCaT	O
+cells	O
+.	O
+
+Treatment	O
+with	O
+iAs	O
+did	O
+not	O
+alter	O
+the	O
+expression	O
+levels	O
+of	O
+KEAP1	O
+mRNA	O
+or	O
+protein	O
+over	O
+either	O
+a	O
+3	O
+or	O
+6	O
+hr	O
+time	O
+course	O
+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+Next	O
+,	O
+we	O
+examined	O
+the	O
+effects	O
+of	O
+iAs	O
+on	O
+the	O
+expression	O
+of	O
+NRF2	O
+mRNA	O
+in	O
+HaCaT	O
+cells	O
+.	O
+
+Exposure	O
+to	O
+iAs	O
+did	O
+not	O
+significantly	O
+alter	O
+the	O
+steady	O
+-	O
+state	O
+levels	O
+of	O
+NRF2	O
+mRNA	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Production	O
+of	O
+NRF2	O
+protein	O
+,	O
+however	O
+,	O
+was	O
+observed	O
+to	O
+increase	O
+in	O
+both	O
+a	O
+dose	O
+-	O
+and	O
+time	O
+-	O
+dependent	O
+manner	O
+(	O
+Figure	O
+4D	O
+)	O
+.	O
+
+To	O
+further	O
+examine	O
+the	O
+stabilization	O
+of	O
+NRF2	O
+protein	O
+by	O
+iAs	O
+,	O
+we	O
+monitored	O
+the	O
+decay	O
+of	O
+basal	O
+and	O
+iAs	O
+-	O
+induced	O
+NRF2	O
+proteins	O
+after	O
+inhibition	O
+of	O
+protein	O
+synthesis	O
+by	O
+CHX	O
+(	O
+Figure	O
+5B	O
+)	O
+.	O
+
+The	O
+results	O
+of	O
+this	O
+analysis	O
+revealed	O
+that	O
+the	O
+NRF2	O
+protein	O
+levels	O
+decrease	O
+by	O
+approximately	O
+50	O
+%	O
+within	O
+30	O
+min	O
+of	O
+treatment	O
+with	O
+CHX	O
+in	O
+cells	O
+that	O
+had	O
+not	O
+been	O
+exposed	O
+to	O
+iAs	O
+.	O
+
+Only	O
+trace	O
+amounts	O
+of	O
+NRF2	O
+are	O
+then	O
+detectable	O
+after	O
+60	O
+min	O
+of	O
+exposure	O
+to	O
+CHX	O
+in	O
+these	O
+cells	O
+.	O
+
+The	O
+HaCaT	O
+cells	O
+were	O
+then	O
+pretreated	O
+with	O
+iAs	O
+for	O
+6	O
+hr	O
+before	O
+their	O
+exposure	O
+to	O
+CHX	O
+in	O
+a	O
+similar	O
+timecourse	O
+experiment	O
+.	O
+
+The	O
+levels	O
+of	O
+NRF2	O
+in	O
+these	O
+iAs	O
+-	O
+treated	O
+cells	O
+were	O
+again	O
+found	O
+to	O
+decrease	O
+by	O
+about	O
+50	O
+%	O
+,	O
+but	O
+only	O
+after	O
+120	O
+min	O
+of	O
+CHX	O
+exposure	O
+.	O
+
+NRF2	O
+plays	O
+a	O
+crucial	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+K16	O
+gene	O
+expression	O
+in	O
+HaCaT	O
+cells	O
+
+To	O
+confirm	O
+the	O
+functional	O
+role	O
+of	O
+NRF2	O
+in	O
+the	O
+induction	O
+of	O
+K16	O
+gene	O
+expression	O
+by	O
+iAs	O
+,	O
+we	O
+investigated	O
+whether	O
+the	O
+expression	O
+of	O
+K16	O
+mRNA	O
+is	O
+induced	O
+by	O
+the	O
+overexpression	O
+of	O
+NRF2	O
+(	O
+WT	O
+-	O
+NRF2	O
+)	O
+in	O
+HaCaT	O
+cells	O
+.	O
+
+We	O
+also	O
+investigated	O
+the	O
+expression	O
+of	O
+the	O
+detoxification	O
+gene	O
+TXN	O
+,	O
+which	O
+is	O
+highly	O
+induced	O
+by	O
+a	O
+variety	O
+of	O
+oxidative	O
+stimuli	O
+through	O
+NRF2	O
+-	O
+mediated	O
+ARE	O
+transactivation	O
+(	O
+Kim	O
+et	O
+al	O
+.	O
+2001	O
+)	O
+.	O
+
+The	O
+expression	O
+of	O
+TXN	O
+gene	O
+in	O
+untransfected	O
+cells	O
+after	O
+treatment	O
+with	O
+iAs	O
+was	O
+stronger	O
+than	O
+that	O
+of	O
+the	O
+control	O
+cells	O
+(	O
+Figure	O
+6A	O
+)	O
+.	O
+
+When	O
+the	O
+cells	O
+were	O
+transfected	O
+with	O
+WT	O
+-	O
+NRF2	O
+and	O
+then	O
+treated	O
+with	O
+or	O
+without	O
+iAs	O
+,	O
+the	O
+expression	O
+of	O
+TXN	O
+mRNA	O
+was	O
+augmented	O
+markedly	O
+compared	O
+with	O
+the	O
+empty	O
+-	O
+vector	O
+control	O
+.	O
+
+Similarly	O
+,	O
+the	O
+expression	O
+of	O
+K16	O
+mRNA	O
+was	O
+also	O
+induced	O
+in	O
+cells	O
+transfected	O
+with	O
+WT	O
+-	O
+NRF2	O
+in	O
+the	O
+absence	O
+or	O
+presence	O
+of	O
+iAs	O
+.	O
+
+We	O
+next	O
+performed	O
+a	O
+transient	O
+transfection	O
+of	O
+HaCaT	O
+cells	O
+with	O
+the	O
+pXK	O
+-	O
+5	O
+-	O
+1	O
+luciferase	O
+vector	O
+together	O
+with	O
+the	O
+WT	O
+-	O
+NRF2	O
+vector	O
+.	O
+
+The	O
+overexpression	O
+of	O
+NRF2	O
+in	O
+increasing	O
+concentrations	O
+resulted	O
+in	O
+significant	O
+enhancement	O
+of	O
+the	O
+ARE	O
+-	O
+mediated	O
+K16	O
+promoter	O
+activation	O
+(	O
+Figure	O
+6B	O
+)	O
+.	O
+
+Discussion	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+showed	O
+for	O
+the	O
+first	O
+time	O
+that	O
+iAs	O
+induces	O
+the	O
+transcriptional	O
+activation	O
+of	O
+K16	O
+in	O
+the	O
+human	B
+keratinocyte	O
+cell	O
+line	O
+,	O
+HaCaT	O
+,	O
+through	O
+the	O
+ARE	O
+present	O
+in	O
+its	O
+gene	O
+promoter	O
+.	O
+
+It	O
+has	O
+been	O
+reported	O
+previously	O
+that	O
+treatment	O
+with	O
+iAs	O
+enhances	O
+the	O
+production	O
+and	O
+translocation	O
+of	O
+NRF2	O
+into	O
+the	O
+nucleus	O
+in	O
+several	O
+cell	O
+types	O
+.	O
+
+However	O
+,	O
+until	O
+now	O
+it	O
+has	O
+remained	O
+uncertain	O
+whether	O
+the	O
+induction	O
+of	O
+NRF2	O
+by	O
+iAs	O
+mediates	O
+the	O
+transcriptional	O
+activation	O
+of	O
+the	O
+K16	O
+gene	O
+in	O
+keratinocytes	O
+.	O
+
+In	O
+our	O
+current	O
+experiments	O
+,	O
+we	O
+demonstrated	O
+that	O
+iAs	O
+elongates	O
+the	O
+half	O
+-	O
+life	O
+of	O
+the	O
+NRF2	O
+protein	O
+,	O
+which	O
+results	O
+in	O
+its	O
+increased	O
+expression	O
+levels	O
+.	O
+
+Furthermore	O
+,	O
+this	O
+iAs	O
+-	O
+induced	O
+NRF2	O
+protein	O
+was	O
+shown	O
+to	O
+bind	O
+to	O
+the	O
+ARE	O
+sequences	O
+in	O
+the	O
+promoter	O
+region	O
+of	O
+the	O
+K16	O
+gene	O
+.	O
+
+Finally	O
+,	O
+by	O
+overexpressing	O
+NRF2	O
+,	O
+we	O
+have	O
+clarified	O
+that	O
+its	O
+induction	O
+is	O
+involved	O
+in	O
+not	O
+only	O
+the	O
+gene	O
+expression	O
+of	O
+the	O
+detoxification	O
+gene	O
+TXN	O
+,	O
+but	O
+also	O
+in	O
+the	O
+upregulation	O
+of	O
+K16	O
+expression	O
+in	O
+HaCaT	O
+cells	O
+through	O
+the	O
+ARE	O
+in	O
+the	O
+K16	O
+gene	O
+promoter	O
+.	O
+
+These	O
+experiments	O
+indicate	O
+an	O
+important	O
+and	O
+novel	O
+function	O
+for	O
+NRF2	O
+in	O
+the	O
+regulation	O
+of	O
+K16	O
+in	O
+keratinocytes	O
+and	O
+also	O
+help	O
+to	O
+further	O
+explain	O
+the	O
+molecular	O
+mechanisms	O
+underlying	O
+arsenic	O
+-	O
+mediated	O
+epidermal	O
+hyperkeratosis	O
+.	O
+
+In	O
+our	O
+present	O
+experiments	O
+,	O
+the	O
+expression	O
+levels	O
+of	O
+K16	O
+mRNA	O
+and	O
+protein	O
+were	O
+indeed	O
+found	O
+to	O
+be	O
+enhanced	O
+by	O
+iAs	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+manner	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+luciferase	O
+assays	O
+of	O
+the	O
+K16	O
+promoter	O
+revealed	O
+that	O
+iAs	O
+enhances	O
+its	O
+activity	O
+in	O
+a	O
+dose	O
+-	O
+dependent	O
+fashion	O
+,	O
+which	O
+is	O
+stimulated	O
+by	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+sites	O
+and	O
+an	O
+ARE	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+The	O
+promoter	O
+of	O
+the	O
+human	B
+K16	O
+gene	O
+was	O
+recently	O
+cloned	O
+and	O
+sequenced	O
+,	O
+and	O
+several	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+sites	O
+were	O
+found	O
+within	O
+the	O
+-	O
+515	O
+-	O
+bp	O
+region	O
+of	O
+the	O
+gene	O
+(	O
+Wang	O
+and	O
+Chang	O
+2003	O
+)	O
+.	O
+
+AP	O
+-	O
+1	O
+transcription	O
+factor	O
+can	O
+be	O
+formed	O
+by	O
+the	O
+dimerization	O
+of	O
+either	O
+Jun	O
+or	O
+Jun	O
+/	O
+Fos	O
+family	O
+members	O
+(	O
+Eferl	O
+and	O
+Wagner	O
+2003	O
+)	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+the	O
+increased	O
+expression	O
+of	O
+c	O
+-	O
+Jun	O
+,	O
+but	O
+not	O
+c	O
+-	O
+Fos	O
+was	O
+evident	O
+in	O
+the	O
+nuclei	O
+of	O
+HaCaT	O
+cells	O
+after	O
+iAs	O
+treatment	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+Our	O
+findings	O
+thus	O
+suggest	O
+that	O
+the	O
+activation	O
+of	O
+c	O
+-	O
+Jun	O
+/	O
+AP	O
+-	O
+1	O
+is	O
+one	O
+of	O
+the	O
+essential	O
+steps	O
+in	O
+the	O
+regulation	O
+of	O
+K16	O
+gene	O
+expression	O
+by	O
+iAs	O
+exposure	O
+in	O
+HaCaT	O
+cells	O
+.	O
+
+It	O
+has	O
+been	O
+well	O
+documented	O
+that	O
+the	O
+ARE	O
+core	O
+sequence	O
+includes	O
+an	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+binding	O
+site	O
+(	O
+TGAC	O
+/	O
+GTCA	O
+)	O
+,	O
+followed	O
+by	O
+a	O
+GC	O
+box	O
+(	O
+Rushmore	O
+et	O
+al	O
+.	O
+1991	O
+;	O
+Xie	O
+et	O
+al	O
+.	O
+1995	O
+)	O
+.	O
+
+We	O
+have	O
+found	O
+in	O
+our	O
+current	O
+analyses	O
+that	O
+the	O
+AP	O
+-	O
+1	O
+-	O
+like	O
+site	O
+within	O
+the	O
+K16	O
+promoter	O
+region	O
+from	O
+-	O
+148	O
+to	O
+-	O
+140	O
+bp	O
+(	O
+5	O
+'	O
+-	O
+GGAGTCAGC	O
+-	O
+3	O
+'	O
+)	O
+resembles	O
+a	O
+consensus	O
+ARE	O
+sequence	O
+.	O
+
+Recent	O
+studies	O
+have	O
+shown	O
+that	O
+AREs	O
+can	O
+be	O
+specifically	O
+bound	O
+by	O
+complexes	O
+of	O
+several	O
+basic	O
+-	O
+leucine	O
+zipper	O
+transcription	O
+factors	O
+,	O
+including	O
+NRF2	O
+(	O
+Ishii	O
+et	O
+al	O
+.	O
+2000	O
+;	O
+Moi	O
+et	O
+al	O
+.	O
+1994	O
+)	O
+.	O
+
+NRF2	O
+heterodimerizes	O
+with	O
+either	O
+AP	O
+-	O
+1	O
+or	O
+small	O
+MAF	O
+(	O
+MAFG	O
+,	O
+MAFK	O
+,	O
+and	O
+MAFF	O
+)	O
+proteins	O
+(	O
+MAF	O
+,	O
+v	O
+-	O
+maf	O
+musculoaponeurotic	O
+fibrosarcoma	O
+oncogene	O
+homolog	O
+)	O
+and	O
+binds	O
+to	O
+the	O
+ARE	O
+to	O
+induce	O
+the	O
+transcription	O
+of	O
+ARE	O
+-	O
+mediated	O
+genes	O
+(	O
+Motohashi	O
+et	O
+al	O
+.	O
+2002	O
+)	O
+.	O
+
+In	O
+the	O
+present	O
+investigation	O
+,	O
+EMSA	O
+and	O
+supershift	O
+assays	O
+showed	O
+that	O
+the	O
+NRF2	O
+proteins	O
+in	O
+the	O
+nuclei	O
+bind	O
+to	O
+the	O
+ARE	O
+sequences	O
+of	O
+K16	O
+promoter	O
+region	O
+after	O
+iAs	O
+exposure	O
+.	O
+
+iAs	O
+-	O
+induced	O
+c	O
+-	O
+Jun	O
+,	O
+however	O
+,	O
+does	O
+not	O
+bind	O
+to	O
+this	O
+ARE	O
+(	O
+Figure	O
+4E	O
+)	O
+.	O
+
+c	O
+-	O
+Jun	O
+may	O
+thus	O
+act	O
+on	O
+other	O
+AP	O
+-	O
+1	O
+sites	O
+within	O
+the	O
+K16	O
+promoter	O
+region	O
+.	O
+
+These	O
+results	O
+also	O
+suggest	O
+that	O
+other	O
+heterodimer	O
+partners	O
+of	O
+NRF2	O
+are	O
+involved	O
+in	O
+the	O
+ARE	O
+regulation	O
+of	O
+K16	O
+promoter	O
+region	O
+underlying	O
+iAs	O
+-	O
+mediated	O
+the	O
+K16	O
+gene	O
+expression	O
+.	O
+
+Gel	O
+shifts	O
+with	O
+an	O
+K16Mut	O
+-	O
+ARE	O
+probe	O
+(	O
+harboring	O
+a	O
+mutation	O
+in	O
+the	O
+ARE	O
+GC	O
+box	O
+)	O
+clearly	O
+show	O
+that	O
+the	O
+ARE	O
+sequence	O
+in	O
+the	O
+K16	O
+promoter	O
+,	O
+particularly	O
+the	O
+terminal	O
+GC	O
+dinucleotide	O
+,	O
+is	O
+essential	O
+for	O
+mediating	O
+iAs	O
+-	O
+induced	O
+K16	O
+transactivation	O
+and	O
+NRF2	O
+binding	O
+(	O
+Figure	O
+4F	O
+)	O
+.	O
+
+Several	O
+investigations	O
+have	O
+suggested	O
+that	O
+the	O
+GC	O
+nucleotides	O
+within	O
+the	O
+ARE	O
+are	O
+essential	O
+for	O
+both	O
+the	O
+basal	O
+and	O
+oxidative	O
+stress	O
+-	O
+induced	O
+activities	O
+of	O
+the	O
+ARE	O
+-	O
+related	O
+genes	O
+,	O
+NAD	O
+(	O
+P	O
+)	O
+H	O
+dehydrogenase	O
+quinone	O
+1	O
+(	O
+NQO1	O
+)	O
+and	O
+glutamate	O
+-	O
+cysteine	O
+ligase	O
+catalytic	O
+subunit	O
+(	O
+GCLC	O
+)	O
+(	O
+Wasserman	O
+and	O
+Fahl	O
+1997	O
+;	O
+Wild	O
+et	O
+al	O
+.	O
+1998	O
+)	O
+.	O
+
+Our	O
+current	O
+results	O
+are	O
+consistent	O
+with	O
+these	O
+earlier	O
+studies	O
+in	O
+showing	O
+that	O
+the	O
+formation	O
+of	O
+the	O
+iAs	O
+-	O
+responsive	O
+NRF2	O
+/	O
+ARE	O
+complexes	O
+is	O
+reduced	O
+by	O
+a	O
+mutation	O
+in	O
+the	O
+GC	O
+box	O
+.	O
+
+Collectively	O
+,	O
+our	O
+present	O
+observations	O
+reveal	O
+a	O
+new	O
+molecular	O
+mechanism	O
+in	O
+which	O
+iAs	O
+-	O
+induced	O
+K16	O
+gene	O
+expression	O
+is	O
+also	O
+regulated	O
+by	O
+activation	O
+NRF2	O
+/	O
+ARE	O
+pathways	O
+.	O
+
+It	O
+has	O
+been	O
+widely	O
+accepted	O
+that	O
+oxidative	O
+stress	O
+disrupts	O
+sequestration	O
+of	O
+NRF2	O
+by	O
+KEAP1	O
+,	O
+permits	O
+NRF2	O
+translocation	O
+to	O
+the	O
+nucleus	O
+,	O
+and	O
+transactivates	O
+the	O
+expression	O
+of	O
+various	O
+NRF2	O
+-	O
+mediated	O
+genes	O
+(	O
+Dinkova	O
+-	O
+Kostova	O
+et	O
+al	O
+.	O
+2002	O
+;	O
+McMahon	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Our	O
+present	O
+study	O
+showed	O
+that	O
+iAs	O
+elongates	O
+the	O
+half	O
+-	O
+life	O
+of	O
+the	O
+NRF2	O
+protein	O
+but	O
+has	O
+no	O
+effects	O
+upon	O
+KEAP1	O
+expression	O
+(	O
+Figure	O
+5	O
+)	O
+.	O
+
+Other	O
+studies	O
+have	O
+also	O
+demonstrated	O
+that	O
+the	O
+production	O
+of	O
+NRF2	O
+is	O
+increased	O
+by	O
+various	O
+inducers	O
+via	O
+posttranscriptional	O
+control	O
+(	O
+Nguyen	O
+et	O
+al	O
+.	O
+2003	O
+;	O
+Stewart	O
+et	O
+al	O
+.	O
+2003	O
+)	O
+.	O
+
+Several	O
+earlier	O
+reports	O
+also	O
+indicated	O
+that	O
+either	O
+oxidative	O
+stress	O
+or	O
+antioxidant	O
+substances	O
+stabilize	O
+the	O
+expression	O
+of	O
+the	O
+NRF2	O
+protein	O
+,	O
+either	O
+by	O
+directly	O
+modifying	O
+the	O
+cysteine	O
+residues	O
+on	O
+KEAP1	O
+to	O
+disrupt	O
+the	O
+NRF2	O
+/	O
+KEAP1	O
+complex	O
+(	O
+Dinkova	O
+-	O
+Kostova	O
+et	O
+al	O
+.	O
+2002	O
+)	O
+or	O
+by	O
+facilitating	O
+the	O
+release	O
+of	O
+NRF2	O
+through	O
+the	O
+phosphorylation	O
+of	O
+the	O
+NRF2	O
+/	O
+KEAP1	O
+complex	O
+(	O
+Bloom	O
+and	O
+Jaiswal	O
+2003	O
+)	O
+.	O
+
+These	O
+findings	O
+are	O
+largely	O
+consistent	O
+with	O
+our	O
+present	O
+finding	O
+that	O
+iAs	O
+stabilizes	O
+the	O
+expression	O
+of	O
+NRF2	O
+in	O
+HaCaT	O
+cells	O
+by	O
+elongating	O
+the	O
+protein	O
+half	O
+-	O
+life	O
+.	O
+
+Recently	O
+,	O
+Wakabayashi	O
+et	O
+al	O
+.	O
+
+(	O
+2003	O
+)	O
+demonstrated	O
+that	O
+NRF2	O
+accumulates	O
+in	O
+the	O
+nucleus	O
+at	O
+constitutively	O
+high	O
+levels	O
+and	O
+produces	O
+various	O
+cytoprotective	O
+genes	O
+in	O
+embryonic	O
+fibroblast	O
+-	O
+and	O
+liver	O
+-	O
+derived	O
+Keap1	O
+-	O
+null	O
+mice	B
+.	O
+
+Surprisingly	O
+,	O
+these	O
+Keap1	O
+-	O
+deficient	O
+mice	B
+also	O
+show	O
+a	O
+thicker	O
+stratum	O
+corneum	O
+epidermis	O
+,	O
+abnormal	O
+keratinization	O
+,	O
+and	O
+cornification	O
+in	O
+the	O
+esophagus	O
+and	O
+forestomach	O
+(	O
+hyperkeratosis	O
+)	O
+.	O
+
+K6	O
+was	O
+found	O
+to	O
+be	O
+strongly	O
+expressed	O
+in	O
+the	O
+esophageal	O
+epithelium	O
+of	O
+these	O
+mice	B
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+K6	O
+is	O
+also	O
+a	O
+target	O
+gene	O
+of	O
+NRF2	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+promoter	O
+of	O
+the	O
+K6	O
+gene	O
+bears	O
+a	O
+remarkable	O
+sequence	O
+similarity	O
+to	O
+the	O
+K16	O
+promoter	O
+(	O
+Jiang	O
+et	O
+al	O
+.	O
+1993	O
+)	O
+.	O
+
+Therefore	O
+,	O
+we	O
+examined	O
+whether	O
+K16	O
+gene	O
+expression	O
+is	O
+also	O
+regulated	O
+by	O
+NRF2	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+the	O
+gene	O
+expression	O
+and	O
+transactivation	O
+of	O
+K16	O
+were	O
+dramatically	O
+induced	O
+by	O
+transfection	O
+with	O
+WT	O
+-	O
+NRF2	O
+via	O
+in	O
+HaCaT	O
+cells	O
+,	O
+clearly	O
+demonstrating	O
+that	O
+NRF2	O
+acts	O
+as	O
+a	O
+direct	O
+transcriptional	O
+regulator	O
+of	O
+the	O
+K16	O
+gene	O
+(	O
+Figure	O
+6	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+also	O
+showed	O
+that	O
+transfection	O
+of	O
+HaCaT	O
+cells	O
+with	O
+WT	O
+-	O
+NRF2	O
+induces	O
+the	O
+expression	O
+of	O
+detoxification	O
+gene	O
+TXN	O
+(	O
+Figure	O
+6A	O
+)	O
+.	O
+
+NRF2	O
+may	O
+thus	O
+have	O
+a	O
+major	O
+role	O
+to	O
+play	O
+in	O
+the	O
+development	O
+of	O
+hyperkeratosis	O
+,	O
+whereas	O
+the	O
+expression	O
+and	O
+induction	O
+of	O
+NRF2	O
+is	O
+implicated	O
+in	O
+cell	O
+protection	O
+against	O
+a	O
+variety	O
+of	O
+genotoxic	O
+and	O
+cytotoxic	O
+effects	O
+.	O
+
+Hence	O
+,	O
+based	O
+on	O
+these	O
+results	O
+and	O
+on	O
+the	O
+findings	O
+from	O
+studies	O
+of	O
+Keap1	O
+knockout	O
+mice	B
+,	O
+iAs	O
+may	O
+both	O
+cause	O
+hyperkeratosis	O
+and	O
+induce	O
+detoxification	O
+enzymes	O
+via	O
+the	O
+modification	O
+of	O
+NRF2	O
+.	O
+
+Given	O
+that	O
+there	O
+are	O
+both	O
+beneficial	O
+and	O
+adverse	O
+effects	O
+of	O
+NRF2	O
+activity	O
+,	O
+caution	O
+will	O
+therefore	O
+be	O
+needed	O
+when	O
+using	O
+antioxidants	O
+for	O
+prevention	O
+and	O
+therapy	O
+.	O
+
+Although	O
+further	O
+investigations	O
+are	O
+needed	O
+,	O
+we	O
+believe	O
+that	O
+our	O
+findings	O
+provide	O
+important	O
+clues	O
+for	O
+the	O
+design	O
+of	O
+future	O
+therapies	O
+for	O
+arsenic	O
+-	O
+mediated	O
+hyperkeratosis	O
+and	O
+for	O
+treatments	O
+involving	O
+the	O
+molecular	O
+targeting	O
+of	O
+NRF2	O
+.	O
+
+Conclusion	O
+
+Our	O
+findings	O
+clearly	O
+demonstrate	O
+that	O
+the	O
+induction	O
+of	O
+the	O
+K16	O
+gene	O
+in	O
+human	B
+keratinocytes	O
+by	O
+iAs	O
+depends	O
+on	O
+NRF2	O
+activation	O
+.	O
+
+Our	O
+results	O
+thus	O
+represent	O
+a	O
+valuable	O
+initial	O
+effort	O
+to	O
+elucidate	O
+the	O
+relationship	O
+between	O
+the	O
+K16	O
+gene	O
+and	O
+the	O
+NRF2	O
+transcription	O
+factor	O
+,	O
+which	O
+may	O
+be	O
+responsible	O
+for	O
+hyperkeratosis	O
+.	O
+
+Identification	O
+and	O
+Analysis	O
+of	O
+Co	O
+-	O
+Occurrence	O
+Networks	O
+with	O
+NetCutter	O
+
+Abstract	O
+
+Background	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+is	O
+a	O
+technique	O
+often	O
+applied	O
+in	O
+text	O
+mining	O
+,	O
+comparative	O
+genomics	O
+,	O
+and	O
+promoter	O
+analysis	O
+.	O
+
+The	O
+methodologies	O
+and	O
+statistical	O
+models	O
+used	O
+to	O
+evaluate	O
+the	O
+significance	O
+of	O
+association	O
+between	O
+co	O
+-	O
+occurring	O
+entities	O
+are	O
+quite	O
+diverse	O
+,	O
+however	O
+.	O
+
+Methodology	O
+/	O
+Principal	O
+Findings	O
+
+We	O
+present	O
+a	O
+general	O
+framework	O
+for	O
+co	O
+-	O
+occurrence	O
+analysis	O
+based	O
+on	O
+a	O
+bipartite	O
+graph	O
+representation	O
+of	O
+the	O
+data	O
+,	O
+a	O
+novel	O
+co	O
+-	O
+occurrence	O
+statistic	O
+,	O
+and	O
+software	O
+performing	O
+co	O
+-	O
+occurrence	O
+analysis	O
+as	O
+well	O
+as	O
+generation	O
+and	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+.	O
+
+We	O
+show	O
+that	O
+the	O
+overall	O
+stringency	O
+of	O
+co	O
+-	O
+occurrence	O
+analysis	O
+depends	O
+critically	O
+on	O
+the	O
+choice	O
+of	O
+the	O
+null	O
+-	O
+model	O
+used	O
+to	O
+evaluate	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrence	O
+and	O
+find	O
+that	O
+random	O
+sampling	O
+from	O
+a	O
+complete	O
+permutation	O
+set	O
+of	O
+the	O
+bipartite	O
+graph	O
+permits	O
+co	O
+-	O
+occurrence	O
+analysis	O
+with	O
+optimal	O
+stringency	O
+.	O
+
+We	O
+show	O
+that	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+is	O
+the	O
+most	O
+natural	O
+co	O
+-	O
+occurrence	O
+probability	O
+distribution	O
+when	O
+vertex	O
+degrees	O
+of	O
+the	O
+bipartite	O
+graph	O
+are	O
+variable	O
+,	O
+which	O
+is	O
+usually	O
+the	O
+case	O
+.	O
+
+Calculation	O
+of	O
+Poisson	O
+-	O
+binomial	O
+P	O
+-	O
+values	O
+is	O
+difficult	O
+,	O
+however	O
+.	O
+
+Therefore	O
+,	O
+we	O
+propose	O
+a	O
+fast	O
+bi	O
+-	O
+binomial	O
+approximation	O
+for	O
+calculation	O
+of	O
+P	O
+-	O
+values	O
+and	O
+show	O
+that	O
+this	O
+statistic	O
+is	O
+superior	O
+to	O
+other	O
+measures	O
+of	O
+association	O
+such	O
+as	O
+the	O
+Jaccard	O
+coefficient	O
+and	O
+the	O
+uncertainty	O
+coefficient	O
+.	O
+
+Furthermore	O
+,	O
+co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+more	O
+than	O
+two	O
+entities	O
+can	O
+be	O
+performed	O
+using	O
+the	O
+same	O
+statistical	O
+model	O
+,	O
+which	O
+leads	O
+to	O
+increased	O
+signal	O
+-	O
+to	O
+-	O
+noise	O
+ratios	O
+,	O
+robustness	O
+towards	O
+noise	O
+,	O
+and	O
+the	O
+identification	O
+of	O
+implicit	O
+relationships	O
+between	O
+co	O
+-	O
+occurring	O
+entities	O
+.	O
+
+Using	O
+NetCutter	O
+,	O
+we	O
+identify	O
+a	O
+novel	O
+protein	O
+biosynthesis	O
+related	O
+set	O
+of	O
+genes	O
+that	O
+are	O
+frequently	O
+coordinately	O
+deregulated	O
+in	O
+human	B
+cancer	O
+related	O
+gene	O
+expression	O
+studies	O
+.	O
+
+NetCutter	O
+is	O
+available	O
+at	O
+http	O
+:	O
+/	O
+/	O
+bio	O
+.	O
+ifom	O
+-	O
+ieo	O
+-	O
+campus	O
+.	O
+it	O
+/	O
+NetCutter	O
+/	O
+)	O
+.	O
+
+Conclusion	O
+
+Our	O
+approach	O
+can	O
+be	O
+applied	O
+to	O
+any	O
+set	O
+of	O
+categorical	O
+data	O
+where	O
+co	O
+-	O
+occurrence	O
+analysis	O
+might	O
+reveal	O
+functional	O
+relationships	O
+such	O
+as	O
+clinical	O
+parameters	O
+associated	O
+with	O
+cancer	O
+subtypes	O
+or	O
+SNPs	O
+associated	O
+with	O
+disease	O
+phenotypes	O
+.	O
+
+The	O
+stringency	O
+of	O
+our	O
+approach	O
+is	O
+expected	O
+to	O
+offer	O
+an	O
+advantage	O
+in	O
+a	O
+variety	O
+of	O
+applications	O
+.	O
+
+Introduction	O
+
+Biological	O
+research	O
+has	O
+experienced	O
+a	O
+paradigm	O
+shift	O
+in	O
+the	O
+last	O
+decade	O
+catalyzed	O
+by	O
+the	O
+availability	O
+of	O
+genome	O
+sequences	O
+and	O
+the	O
+resulting	O
+development	O
+of	O
+high	O
+-	O
+throughput	O
+technologies	O
+.	O
+
+The	O
+large	O
+data	O
+volumes	O
+produced	O
+by	O
+these	O
+novel	O
+technologies	O
+are	O
+often	O
+published	O
+as	O
+supplementary	O
+material	O
+and	O
+/	O
+or	O
+stored	O
+in	O
+extensive	O
+data	O
+repositories	O
+[	O
+1	O
+]	O
+.	O
+
+Functional	O
+interpretation	O
+of	O
+these	O
+data	O
+is	O
+an	O
+ongoing	O
+challenge	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+,	O
+based	O
+on	O
+the	O
+hypothesis	O
+that	O
+co	O
+-	O
+occurring	O
+entities	O
+are	O
+functionally	O
+linked	O
+,	O
+is	O
+a	O
+technique	O
+that	O
+has	O
+been	O
+used	O
+in	O
+three	O
+main	O
+areas	O
+of	O
+biological	O
+research	O
+:	O
+
+Co	O
+-	O
+occurrence	O
+of	O
+genes	O
+in	O
+sequenced	O
+genomes	O
+relies	O
+on	O
+the	O
+fact	O
+that	O
+proteins	O
+do	O
+not	O
+function	O
+in	O
+isolation	O
+and	O
+are	O
+dependent	O
+on	O
+other	O
+proteins	O
+,	O
+either	O
+as	O
+direct	O
+binding	O
+partners	O
+,	O
+or	O
+as	O
+catalysts	O
+of	O
+substrates	O
+.	O
+
+Thus	O
+,	O
+when	O
+two	O
+proteins	O
+significantly	O
+co	O
+-	O
+occur	O
+in	O
+a	O
+large	O
+number	O
+of	O
+genomes	O
+or	O
+can	O
+be	O
+observed	O
+as	O
+fusion	O
+proteins	O
+in	O
+a	O
+subset	O
+of	O
+genomes	O
+,	O
+they	O
+are	O
+likely	O
+to	O
+be	O
+binding	O
+partners	O
+or	O
+enzymes	O
+needed	O
+for	O
+a	O
+specific	O
+metabolic	O
+pathway	O
+.	O
+
+Examples	O
+of	O
+those	O
+studies	O
+have	O
+been	O
+reported	O
+by	O
+[	O
+2	O
+]	O
+-	O
+[	O
+7	O
+]	O
+.	O
+
+Text	O
+mining	O
+is	O
+a	O
+quickly	O
+evolving	O
+field	O
+that	O
+aims	O
+at	O
+developing	O
+technologies	O
+helping	O
+to	O
+cope	O
+with	O
+the	O
+functional	O
+interpretation	O
+of	O
+large	O
+volumes	O
+of	O
+publications	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+of	O
+gene	O
+names	O
+in	O
+publication	O
+abstracts	O
+,	O
+entire	O
+publications	O
+,	O
+or	O
+other	O
+gene	O
+-	O
+related	O
+databases	O
+has	O
+been	O
+used	O
+to	O
+derive	O
+co	O
+-	O
+occurrence	O
+networks	O
+with	O
+clear	O
+evidence	O
+that	O
+edges	O
+in	O
+those	O
+networks	O
+are	O
+reflecting	O
+functionally	O
+relevant	O
+relationships	O
+[	O
+8	O
+]	O
+-	O
+[	O
+11	O
+]	O
+.	O
+
+Gene	O
+names	O
+have	O
+also	O
+been	O
+analyzed	O
+for	O
+co	O
+-	O
+occurrence	O
+with	O
+other	O
+entities	O
+such	O
+as	O
+mutations	O
+[	O
+12	O
+]	O
+,	O
+chemical	O
+compounds	O
+[	O
+13	O
+]	O
+,	O
+and	O
+disease	O
+related	O
+keywords	O
+[	O
+14	O
+]	O
+.	O
+
+From	O
+the	O
+resulting	O
+networks	O
+,	O
+hypotheses	O
+about	O
+candidate	O
+genes	O
+involved	O
+in	O
+inherited	O
+diseases	O
+and	O
+drug	O
+targets	O
+can	O
+be	O
+derived	O
+.	O
+
+Clustering	O
+of	O
+gene	O
+related	O
+publications	O
+using	O
+keywords	O
+has	O
+been	O
+applied	O
+to	O
+enhance	O
+the	O
+quality	O
+of	O
+gene	O
+expression	O
+clusters	O
+[	O
+15	O
+]	O
+,	O
+[	O
+16	O
+]	O
+.	O
+
+More	O
+general	O
+(	O
+non	O
+gene	O
+-	O
+centric	O
+)	O
+approaches	O
+try	O
+to	O
+organize	O
+the	O
+literature	O
+into	O
+functional	O
+areas	O
+based	O
+on	O
+co	O
+-	O
+occurrence	O
+of	O
+MeSH	O
+terms	O
+,	O
+keywords	O
+,	O
+diseases	O
+,	O
+phenotypes	O
+,	O
+chemicals	O
+,	O
+and	O
+similar	O
+objects	O
+of	O
+biomedical	O
+research	O
+interest	O
+[	O
+17	O
+]	O
+-	O
+[	O
+21	O
+]	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+transcription	O
+factor	O
+binding	O
+motifs	O
+has	O
+been	O
+carried	O
+out	O
+in	O
+a	O
+variety	O
+of	O
+slightly	O
+differing	O
+ways	O
+in	O
+a	O
+wide	O
+range	O
+of	O
+organisms	O
+,	O
+including	O
+humans	B
+.	O
+
+[	O
+22	O
+]	O
+-	O
+[	O
+33	O
+]	O
+.	O
+
+The	O
+underlying	O
+hypothesis	O
+is	O
+that	O
+co	O
+-	O
+regulated	O
+genes	O
+,	O
+identified	O
+usually	O
+by	O
+gene	O
+expression	O
+studies	O
+,	O
+should	O
+contain	O
+specific	O
+combinations	O
+of	O
+transcription	O
+factor	O
+binding	O
+motifs	O
+in	O
+their	O
+upstream	O
+regulatory	O
+regions	O
+,	O
+the	O
+identification	O
+of	O
+which	O
+would	O
+allow	O
+the	O
+reverse	O
+-	O
+engineering	O
+of	O
+transcription	O
+regulatory	O
+networks	O
+[	O
+34	O
+]	O
+.	O
+
+We	O
+have	O
+recently	O
+applied	O
+co	O
+-	O
+occurrence	O
+analysis	O
+to	O
+studying	O
+published	O
+gene	O
+expression	O
+signatures	O
+and	O
+showed	O
+that	O
+co	O
+-	O
+occurrence	O
+patterns	O
+of	O
+genes	O
+reflect	O
+cancer	O
+signaling	O
+pathways	O
+[	O
+35	O
+]	O
+.	O
+
+Although	O
+co	O
+-	O
+occurrence	O
+analysis	O
+has	O
+a	O
+respectable	O
+history	O
+,	O
+the	O
+methodologies	O
+used	O
+in	O
+the	O
+studies	O
+mentioned	O
+above	O
+could	O
+not	O
+be	O
+easily	O
+applied	O
+to	O
+studying	O
+gene	O
+expression	O
+signatures	O
+.	O
+
+There	O
+are	O
+three	O
+main	O
+reasons	O
+that	O
+dictated	O
+the	O
+use	O
+of	O
+a	O
+different	O
+approach	O
+.	O
+
+First	O
+,	O
+gene	O
+expression	O
+signatures	O
+can	O
+vary	O
+in	O
+size	O
+by	O
+orders	O
+of	O
+magnitude	O
+.	O
+
+Obviously	O
+,	O
+the	O
+larger	O
+a	O
+signature	O
+the	O
+more	O
+likely	O
+it	O
+is	O
+to	O
+find	O
+two	O
+or	O
+more	O
+genes	O
+co	O
+-	O
+occurring	O
+in	O
+that	O
+signature	O
+.	O
+
+Thus	O
+,	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrences	O
+must	O
+be	O
+evaluated	O
+in	O
+the	O
+presence	O
+of	O
+considerable	O
+heterogeneity	O
+of	O
+co	O
+-	O
+occurrence	O
+probabilities	O
+among	O
+gene	O
+lists	O
+.	O
+
+As	O
+a	O
+consequence	O
+,	O
+the	O
+statistics	O
+used	O
+to	O
+evaluate	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrence	O
+events	O
+must	O
+reflect	O
+this	O
+heterogeneity	O
+.	O
+
+In	O
+particular	O
+,	O
+it	O
+must	O
+be	O
+based	O
+on	O
+list	O
+-	O
+specific	O
+co	O
+-	O
+occurrence	O
+probabilities	O
+.	O
+
+Second	O
+,	O
+in	O
+the	O
+vast	O
+majority	O
+of	O
+previous	O
+studies	O
+,	O
+co	O
+-	O
+occurrence	O
+is	O
+analyzed	O
+for	O
+pair	O
+-	O
+wise	O
+combinations	O
+of	O
+co	O
+-	O
+occurring	O
+entities	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+resulting	O
+stringency	O
+of	O
+this	O
+approach	O
+is	O
+not	O
+adequate	O
+for	O
+the	O
+analysis	O
+of	O
+published	O
+gene	O
+expression	O
+signatures	O
+[	O
+35	O
+]	O
+.	O
+
+Third	O
+,	O
+the	O
+null	O
+-	O
+model	O
+against	O
+which	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrences	O
+is	O
+tested	O
+does	O
+not	O
+work	O
+well	O
+for	O
+gene	O
+expression	O
+signatures	O
+.	O
+
+A	O
+common	O
+procedure	O
+is	O
+to	O
+use	O
+generic	O
+randomization	O
+of	O
+the	O
+entire	O
+data	O
+set	O
+under	O
+analysis	O
+or	O
+to	O
+select	O
+subsets	O
+of	O
+data	O
+entries	O
+randomly	O
+for	O
+comparison	O
+purposes	O
+.	O
+
+However	O
+,	O
+gene	O
+expression	O
+signatures	O
+are	O
+composed	O
+of	O
+distinct	O
+gene	O
+sets	O
+and	O
+the	O
+null	O
+-	O
+model	O
+must	O
+maintain	O
+this	O
+property	O
+,	O
+which	O
+is	O
+not	O
+guaranteed	O
+using	O
+these	O
+approaches	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+list	O
+-	O
+specific	O
+nature	O
+of	O
+co	O
+-	O
+occurrence	O
+probabilities	O
+cannot	O
+be	O
+dealt	O
+with	O
+properly	O
+.	O
+
+NetCutter	O
+was	O
+developed	O
+to	O
+address	O
+these	O
+challenges	O
+and	O
+to	O
+provide	O
+a	O
+generic	O
+tool	O
+for	O
+generating	O
+and	O
+analyzing	O
+co	O
+-	O
+occurrence	O
+networks	O
+.	O
+
+Although	O
+NetCutter	O
+has	O
+been	O
+developed	O
+for	O
+the	O
+analysis	O
+of	O
+gene	O
+expression	O
+signatures	O
+,	O
+it	O
+is	O
+based	O
+on	O
+abstract	O
+concepts	O
+that	O
+make	O
+it	O
+applicable	O
+to	O
+a	O
+wide	O
+variety	O
+of	O
+problems	O
+.	O
+
+The	O
+input	O
+is	O
+represented	O
+by	O
+a	O
+bipartite	O
+graph	O
+that	O
+is	O
+composed	O
+of	O
+list	O
+-	O
+entry	O
+pairs	O
+,	O
+which	O
+are	O
+stored	O
+in	O
+tab	O
+-	O
+separated	O
+text	O
+format	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+of	O
+entries	O
+in	O
+lists	O
+is	O
+analyzed	O
+using	O
+pair	O
+-	O
+wise	O
+or	O
+higher	O
+order	O
+combinations	O
+of	O
+entries	O
+.	O
+
+The	O
+significance	O
+of	O
+co	O
+-	O
+occurrence	O
+is	O
+tested	O
+using	O
+a	O
+novel	O
+bi	O
+-	O
+binomial	O
+approximation	O
+of	O
+Poisson	O
+-	O
+binomial	O
+statistics	O
+(	O
+which	O
+is	O
+a	O
+binomial	O
+distribution	O
+with	O
+trial	O
+specific	O
+probabilities	O
+)	O
+that	O
+handles	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+properly	O
+and	O
+provides	O
+a	O
+novel	O
+measure	O
+of	O
+association	O
+that	O
+is	O
+found	O
+to	O
+be	O
+superior	O
+to	O
+the	O
+Jaccard	O
+and	O
+the	O
+uncertainty	O
+coefficients	O
+.	O
+
+Occurrence	O
+probabilities	O
+are	O
+obtained	O
+from	O
+an	O
+edge	O
+-	O
+swapping	O
+procedure	O
+that	O
+maintains	O
+vertex	O
+degrees	O
+in	O
+the	O
+underlying	O
+bipartite	O
+graph	O
+and	O
+distinct	O
+sets	O
+of	O
+entries	O
+per	O
+list	O
+.	O
+
+As	O
+we	O
+shall	O
+see	O
+below	O
+,	O
+this	O
+procedure	O
+has	O
+a	O
+number	O
+of	O
+advantages	O
+over	O
+other	O
+possible	O
+null	O
+-	O
+models	O
+and	O
+permits	O
+co	O
+-	O
+occurrence	O
+analysis	O
+with	O
+near	O
+maximum	O
+stringency	O
+.	O
+
+Last	O
+but	O
+not	O
+least	O
+,	O
+NetCutter	O
+is	O
+equipped	O
+with	O
+a	O
+number	O
+of	O
+algorithms	O
+for	O
+the	O
+identification	O
+of	O
+network	O
+communities	O
+,	O
+vertex	O
+ranking	O
+,	O
+and	O
+convenience	O
+tools	O
+needed	O
+in	O
+the	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+,	O
+or	O
+any	O
+undirected	O
+graph	O
+.	O
+
+We	O
+illustrate	O
+the	O
+utility	O
+of	O
+NetCutter	O
+in	O
+the	O
+identification	O
+of	O
+corresponding	O
+clusters	O
+of	O
+genes	O
+and	O
+publications	O
+from	O
+the	O
+PubLiME	O
+data	O
+set	O
+.	O
+
+PubLiME	O
+(	O
+Published	O
+Lists	O
+of	O
+Microarray	O
+Experiments	O
+)	O
+is	O
+a	O
+repository	O
+of	O
+published	O
+cancer	O
+related	O
+gene	O
+expression	O
+signatures	O
+(	O
+http	O
+:	O
+/	O
+/	O
+bio	O
+.	O
+ifom	O
+-	O
+ieo	O
+-	O
+campus	O
+.	O
+it	O
+/	O
+Publime	O
+)	O
+.	O
+
+The	O
+concept	O
+of	O
+cluster	O
+correspondence	O
+follows	O
+from	O
+the	O
+bipartite	O
+graph	O
+representation	O
+of	O
+the	O
+data	O
+.	O
+
+Reversing	O
+the	O
+list	O
+-	O
+entry	O
+order	O
+in	O
+the	O
+bipartite	O
+graph	O
+permits	O
+identifying	O
+communities	O
+of	O
+entries	O
+as	O
+well	O
+as	O
+communities	O
+of	O
+lists	O
+.	O
+
+We	O
+show	O
+that	O
+communities	O
+of	O
+publications	O
+corresponding	O
+to	O
+communities	O
+of	O
+genes	O
+in	O
+the	O
+PubLiME	O
+data	O
+set	O
+can	O
+be	O
+used	O
+to	O
+generate	O
+hypotheses	O
+about	O
+the	O
+putative	O
+function	O
+of	O
+gene	O
+communities	O
+.	O
+
+Results	O
+
+The	O
+bipartite	O
+graph	O
+model	O
+of	O
+co	O
+-	O
+occurrence	O
+analysis	O
+
+Co	O
+-	O
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+using	O
+NetCutter	O
+is	O
+based	O
+on	O
+the	O
+abstraction	O
+of	O
+list	O
+-	O
+entry	O
+pairs	O
+.	O
+
+Any	O
+entity	O
+that	O
+co	O
+-	O
+occurs	O
+with	O
+some	O
+other	O
+entity	O
+must	O
+be	O
+confined	O
+to	O
+some	O
+sort	O
+of	O
+container	O
+where	O
+co	O
+-	O
+occurrence	O
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+observed	O
+.	O
+
+For	O
+example	O
+,	O
+in	O
+the	O
+case	O
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+gene	O
+name	O
+co	O
+-	O
+occurrence	O
+in	O
+PubMed	O
+abstracts	O
+,	O
+the	O
+abstract	O
+is	O
+the	O
+container	O
+and	O
+the	O
+gene	O
+names	O
+are	O
+the	O
+co	O
+-	O
+occurring	O
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+.	O
+
+Similarly	O
+,	O
+co	O
+-	O
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+binding	O
+motifs	O
+is	O
+observed	O
+in	O
+gene	O
+promoters	O
+.	O
+
+The	O
+promoters	O
+are	O
+the	O
+containers	O
+where	O
+motif	O
+entities	O
+co	O
+-	O
+occur	O
+.	O
+
+The	O
+containers	O
+generally	O
+host	O
+more	O
+than	O
+one	O
+entity	O
+(	O
+otherwise	O
+co	O
+-	O
+occurrence	O
+would	O
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+)	O
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+can	O
+be	O
+conveniently	O
+interpreted	O
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+
+The	O
+co	O
+-	O
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+list	O
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+.	O
+
+Lists	O
+and	O
+entries	O
+form	O
+a	O
+bipartite	O
+graph	O
+with	O
+one	O
+part	O
+of	O
+the	O
+graph	O
+representing	O
+lists	O
+and	O
+the	O
+other	O
+part	O
+representing	O
+entries	O
+.	O
+
+The	O
+presence	O
+of	O
+a	O
+given	O
+entry	O
+in	O
+a	O
+given	O
+list	O
+is	O
+indicated	O
+by	O
+an	O
+edge	O
+between	O
+the	O
+corresponding	O
+list	O
+and	O
+entry	O
+vertices	O
+.	O
+
+It	O
+is	O
+required	O
+that	O
+each	O
+entry	O
+can	O
+be	O
+linked	O
+to	O
+the	O
+same	O
+list	O
+only	O
+once	O
+.	O
+
+Without	O
+loss	O
+of	O
+generality	O
+,	O
+let	O
+'	O
+s	O
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+genes	O
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+
+This	O
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+-	O
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+Occurrence	O
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+
+The	O
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+A	O
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+This	O
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+The	O
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+First	O
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+Second	O
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+Calculating	O
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+.	O
+
+In	O
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+,	O
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+both	O
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+
+In	O
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+,	O
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+.	O
+
+From	O
+these	O
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+,	O
+it	O
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+to	O
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+-	O
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+
+A	O
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+,	O
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+
+Gene1	O
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+
+Therefore	O
+,	O
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+-	O
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+,	O
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+,	O
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+
+In	O
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+,	O
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+0	O
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+
+Only	O
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+
+Since	O
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+,	O
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+
+Expected	O
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+As	O
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+comparing	O
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+-	O
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+-	O
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+
+The	O
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+If	O
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+
+The	O
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+
+If	O
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+
+Larger	O
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+-	O
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+The	O
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+
+A	O
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+-	O
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+-	O
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+
+The	O
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+-	O
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+
+Thus	O
+,	O
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+-	O
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+-	O
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+-	O
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+
+Nl	O
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+We	O
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+The	O
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+The	O
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+The	O
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+2A	O
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+However	O
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+The	O
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+However	O
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+-	O
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+In	O
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+As	O
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+In	O
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+The	O
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+More	O
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+
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+
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+
+Since	O
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+
+By	O
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+criteria	O
+,	O
+the	O
+ES	O
+model	O
+is	O
+the	O
+most	O
+stringent	O
+of	O
+all	O
+models	O
+tested	O
+.	O
+
+The	O
+ES	O
+model	O
+as	O
+an	O
+approximation	O
+of	O
+the	O
+permutation	O
+null	O
+-	O
+model	O
+
+The	O
+data	O
+shown	O
+above	O
+have	O
+revealed	O
+that	O
+the	O
+ES	O
+model	O
+is	O
+the	O
+best	O
+of	O
+the	O
+models	O
+tested	O
+.	O
+
+One	O
+may	O
+wonder	O
+,	O
+however	O
+,	O
+whether	O
+yet	O
+more	O
+effective	O
+null	O
+-	O
+models	O
+can	O
+be	O
+found	O
+.	O
+
+An	O
+obvious	O
+choice	O
+would	O
+be	O
+the	O
+permutation	O
+model	O
+.	O
+
+In	O
+the	O
+permutation	O
+model	O
+,	O
+a	O
+complete	O
+permutation	O
+set	O
+of	O
+the	O
+bipartite	O
+graph	O
+is	O
+created	O
+such	O
+that	O
+each	O
+list	O
+is	O
+composed	O
+of	O
+distinct	O
+sets	O
+of	O
+genes	O
+.	O
+
+The	O
+number	O
+of	O
+graphs	O
+where	O
+a	O
+gene	O
+is	O
+present	O
+in	O
+a	O
+given	O
+list	O
+divided	O
+by	O
+the	O
+total	O
+number	O
+of	O
+permutations	O
+then	O
+provides	O
+the	O
+occurrence	O
+probability	O
+estimate	O
+.	O
+
+The	O
+permutation	O
+model	O
+is	O
+the	O
+ideal	O
+null	O
+-	O
+model	O
+because	O
+it	O
+is	O
+exhaustive	O
+.	O
+
+The	O
+problem	O
+is	O
+that	O
+a	O
+complete	O
+permutation	O
+set	O
+of	O
+bipartite	O
+graphs	O
+of	O
+some	O
+complexity	O
+is	O
+very	O
+time	O
+consuming	O
+to	O
+calculate	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+simple	O
+bipartite	O
+graph	O
+from	O
+Fig	O
+.	O
+
+1A	O
+is	O
+part	O
+of	O
+a	O
+permutation	O
+set	O
+of	O
+455	O
+graphs	O
+.	O
+
+The	O
+number	O
+of	O
+permutations	O
+is	O
+increasing	O
+quickly	O
+as	O
+the	O
+numbers	O
+of	O
+genes	O
+and	O
+lists	O
+grow	O
+.	O
+
+However	O
+,	O
+since	O
+edge	O
+-	O
+swapping	O
+ensures	O
+that	O
+gene	O
+lists	O
+are	O
+composed	O
+of	O
+distinct	O
+sets	O
+of	O
+genes	O
+,	O
+each	O
+edge	O
+-	O
+swap	O
+produces	O
+a	O
+graph	O
+that	O
+is	O
+part	O
+of	O
+the	O
+permutation	O
+set	O
+of	O
+the	O
+bipartite	O
+graph	O
+.	O
+
+Edge	O
+-	O
+swapping	O
+can	O
+thus	O
+be	O
+viewed	O
+as	O
+a	O
+random	O
+sampling	O
+procedure	O
+from	O
+the	O
+permutation	O
+set	O
+of	O
+the	O
+bipartite	O
+graph	O
+.	O
+
+Therefore	O
+,	O
+occurrence	O
+probability	O
+estimates	O
+derived	O
+by	O
+edge	O
+-	O
+swapping	O
+should	O
+approximate	O
+those	O
+obtained	O
+from	O
+the	O
+permutation	O
+model	O
+.	O
+
+We	O
+generated	O
+a	O
+complete	O
+permutation	O
+set	O
+of	O
+the	O
+graph	O
+shown	O
+in	O
+Fig	O
+.	O
+
+1A	O
+to	O
+verify	O
+this	O
+hypothesis	O
+.	O
+
+The	O
+results	O
+are	O
+shown	O
+in	O
+Fig	O
+.	O
+
+3	O
+.	O
+
+Fig	O
+.	O
+
+3A	O
+shows	O
+how	O
+the	O
+number	O
+of	O
+possible	O
+permutations	O
+can	O
+be	O
+calculated	O
+.	O
+
+Gene1	O
+is	O
+present	O
+in	O
+all	O
+lists	O
+and	O
+does	O
+not	O
+have	O
+an	O
+impact	O
+on	O
+the	O
+total	O
+number	O
+of	O
+permutations	O
+.	O
+
+Gene2	O
+,	O
+having	O
+vertex	O
+degree	O
+two	O
+,	O
+is	O
+present	O
+in	O
+two	O
+out	O
+of	O
+three	O
+lists	O
+in	O
+one	O
+out	O
+of	O
+three	O
+possible	O
+ways	O
+.	O
+
+The	O
+remaining	O
+genes	O
+have	O
+vertex	O
+degree	O
+1	O
+and	O
+can	O
+be	O
+freely	O
+chosen	O
+to	O
+fill	O
+the	O
+empty	O
+slots	O
+.	O
+
+We	O
+can	O
+now	O
+count	O
+exactly	O
+how	O
+many	O
+times	O
+a	O
+gene	O
+is	O
+linked	O
+to	O
+a	O
+list	O
+and	O
+divide	O
+these	O
+counts	O
+by	O
+455	O
+,	O
+the	O
+size	O
+of	O
+the	O
+permutation	O
+set	O
+,	O
+to	O
+obtain	O
+exact	O
+occurrence	O
+probabilities	O
+.	O
+
+These	O
+numbers	O
+are	O
+shown	O
+in	O
+graphical	O
+form	O
+in	O
+Fig	O
+.	O
+
+3B	O
+and	O
+in	O
+numerical	O
+form	O
+in	O
+Fig	O
+.	O
+
+3C	O
+.	O
+
+Fig	O
+.	O
+
+3B	O
+also	O
+shows	O
+the	O
+occurrence	O
+probability	O
+estimates	O
+obtained	O
+by	O
+edge	O
+-	O
+swapping	O
+side	O
+-	O
+by	O
+-	O
+side	O
+to	O
+the	O
+exact	O
+occurrence	O
+probabilities	O
+.	O
+
+The	O
+graph	O
+in	O
+Fig	O
+.	O
+
+1A	O
+was	O
+subjected	O
+to	O
+edge	O
+-	O
+swapping	O
+1000	O
+times	O
+and	O
+the	O
+number	O
+of	O
+times	O
+a	O
+gene	O
+was	O
+found	O
+present	O
+in	O
+a	O
+list	O
+was	O
+divided	O
+by	O
+1000	O
+to	O
+obtain	O
+the	O
+occurrence	O
+probability	O
+.	O
+
+At	O
+each	O
+run	O
+,	O
+100	O
+random	O
+edge	O
+swaps	O
+were	O
+performed	O
+to	O
+ensure	O
+complete	O
+randomization	O
+of	O
+the	O
+graph	O
+.	O
+
+This	O
+procedure	O
+was	O
+repeated	O
+10	O
+times	O
+and	O
+the	O
+mean	O
+and	O
+standard	O
+deviation	O
+of	O
+occurrence	O
+probability	O
+estimates	O
+for	O
+each	O
+gene	O
+in	O
+each	O
+list	O
+are	O
+shown	O
+.	O
+
+In	O
+all	O
+cases	O
+,	O
+the	O
+mean	O
+differs	O
+from	O
+the	O
+real	O
+probability	O
+by	O
+less	O
+than	O
+two	O
+standard	O
+deviations	O
+,	O
+in	O
+most	O
+cases	O
+by	O
+less	O
+than	O
+one	O
+standard	O
+deviation	O
+.	O
+
+Thus	O
+,	O
+edge	O
+-	O
+swapping	O
+provides	O
+reliable	O
+estimates	O
+of	O
+exact	O
+occurrence	O
+probabilities	O
+as	O
+determined	O
+from	O
+a	O
+complete	O
+permutation	O
+set	O
+.	O
+
+As	O
+an	O
+interesting	O
+observation	O
+,	O
+we	O
+provide	O
+evidence	O
+that	O
+occurrence	O
+probabilities	O
+are	O
+non	O
+-	O
+linear	O
+functions	O
+of	O
+vertex	O
+degrees	O
+in	O
+the	O
+edge	O
+-	O
+swapping	O
+model	O
+.	O
+
+This	O
+is	O
+illustrated	O
+in	O
+Fig	O
+.	O
+
+3C	O
+.	O
+
+Individual	O
+and	O
+average	O
+occurrence	O
+probabilities	O
+are	O
+shown	O
+as	O
+a	O
+function	O
+of	O
+gene	O
+and	O
+list	O
+vertex	O
+degrees	O
+.	O
+
+Non	O
+-	O
+linearity	O
+of	O
+individual	O
+occurrence	O
+probabilities	O
+can	O
+be	O
+verified	O
+from	O
+the	O
+counts	O
+table	O
+underneath	O
+the	O
+plots	O
+.	O
+
+However	O
+,	O
+the	O
+average	O
+occurrence	O
+probability	O
+is	O
+found	O
+to	O
+depend	O
+on	O
+vertex	O
+degrees	O
+in	O
+a	O
+linear	O
+fashion	O
+instead	O
+.	O
+
+This	O
+is	O
+a	O
+consequence	O
+of	O
+the	O
+fact	O
+that	O
+occurrence	O
+probabilities	O
+of	O
+a	O
+gene	O
+over	O
+all	O
+lists	O
+add	O
+up	O
+to	O
+the	O
+gene	O
+vertex	O
+degree	O
+and	O
+that	O
+the	O
+occurrence	O
+probabilities	O
+of	O
+all	O
+genes	O
+for	O
+a	O
+given	O
+list	O
+add	O
+up	O
+to	O
+the	O
+list	O
+vertex	O
+degree	O
+.	O
+
+At	O
+the	O
+same	O
+time	O
+,	O
+since	O
+the	O
+most	O
+stringent	O
+permutation	O
+based	O
+null	O
+-	O
+model	O
+predicts	O
+non	O
+-	O
+linear	O
+dependencies	O
+of	O
+individual	O
+occurrence	O
+probabilities	O
+on	O
+vertex	O
+degrees	O
+,	O
+assuming	O
+such	O
+linearity	O
+in	O
+statistical	O
+models	O
+of	O
+co	O
+-	O
+occurrence	O
+will	O
+be	O
+linked	O
+to	O
+loss	O
+of	O
+stringency	O
+.	O
+
+We	O
+conclude	O
+that	O
+the	O
+ES	O
+null	O
+-	O
+model	O
+is	O
+the	O
+null	O
+-	O
+model	O
+that	O
+permits	O
+co	O
+-	O
+occurrence	O
+analysis	O
+with	O
+the	O
+highest	O
+stringency	O
+among	O
+the	O
+models	O
+tested	O
+and	O
+that	O
+it	O
+closely	O
+approximates	O
+occurrence	O
+probabilities	O
+derived	O
+from	O
+an	O
+ideal	O
+permutation	O
+model	O
+.	O
+
+The	O
+increased	O
+stringency	O
+of	O
+the	O
+ES	O
+model	O
+over	O
+other	O
+models	O
+is	O
+a	O
+consequence	O
+of	O
+higher	O
+occurrence	O
+probabilities	O
+for	O
+genes	O
+and	O
+list	O
+with	O
+high	O
+vertex	O
+degrees	O
+,	O
+which	O
+are	O
+giving	O
+rise	O
+to	O
+a	O
+large	O
+part	O
+of	O
+all	O
+co	O
+-	O
+occurrences	O
+in	O
+the	O
+bipartite	O
+graph	O
+.	O
+
+Since	O
+large	O
+occurrence	O
+probabilities	O
+make	O
+co	O
+-	O
+occurrence	O
+more	O
+likely	O
+,	O
+the	O
+analysis	O
+becomes	O
+more	O
+stringent	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+probabilities	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+can	O
+be	O
+thought	O
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+as	O
+a	O
+Bernoulli	O
+experiment	O
+with	O
+a	O
+binomial	O
+outcome	O
+(	O
+a	O
+given	O
+combination	O
+of	O
+entries	O
+is	O
+either	O
+present	O
+or	O
+not	O
+present	O
+in	O
+a	O
+given	O
+list	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+Binomial	O
+distribution	O
+(	O
+BD	O
+)	O
+is	O
+a	O
+natural	O
+choice	O
+for	O
+judging	O
+the	O
+significance	O
+of	O
+the	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+.	O
+
+However	O
+,	O
+the	O
+BD	O
+is	O
+defined	O
+for	O
+a	O
+probability	O
+of	O
+success	O
+which	O
+is	O
+equal	O
+in	O
+all	O
+trials	O
+.	O
+
+The	O
+list	O
+-	O
+specific	O
+nature	O
+of	O
+occurrence	O
+probabilities	O
+is	O
+not	O
+compatible	O
+with	O
+this	O
+condition	O
+(	O
+analysis	O
+of	O
+each	O
+list	O
+represents	O
+one	O
+trial	O
+)	O
+,	O
+which	O
+means	O
+that	O
+co	O
+-	O
+occurrence	O
+analysis	O
+in	O
+the	O
+presence	O
+of	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+is	O
+better	O
+described	O
+as	O
+a	O
+series	O
+of	O
+Poisson	O
+trials	O
+,	O
+where	O
+the	O
+probability	O
+of	O
+success	O
+varies	O
+from	O
+trial	O
+to	O
+trial	O
+.	O
+
+Therefore	O
+,	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrences	O
+must	O
+be	O
+evaluated	O
+using	O
+a	O
+binomial	O
+distribution	O
+with	O
+trial	O
+-	O
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+probabilities	O
+,	O
+i	O
+.	O
+e	O
+.	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+(	O
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+)	O
+.	O
+
+The	O
+probability	O
+of	O
+success	O
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+-	O
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+probabilities	O
+for	O
+the	O
+combination	O
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+study	O
+.	O
+
+The	O
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+need	O
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+is	O
+equal	O
+to	O
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+module	O
+size	O
+,	O
+i	O
+.	O
+e	O
+.	O
+the	O
+number	O
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+genes	O
+whose	O
+combination	O
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+studied	O
+.	O
+
+An	O
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+number	O
+of	O
+co	O
+-	O
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+a	O
+combination	O
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+genes	O
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+then	O
+be	O
+evaluated	O
+using	O
+the	O
+PBD	O
+,	O
+which	O
+is	O
+given	O
+by	O
+the	O
+formula	O
+[	O
+36	O
+]	O
+:	O
+(	O
+18	O
+)	O
+
+The	O
+structure	O
+of	O
+this	O
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+formula	O
+used	O
+to	O
+calculate	O
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+,	O
+except	O
+that	O
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+replaced	O
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+summation	O
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+terms	O
+,	O
+which	O
+makes	O
+calculation	O
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+P	O
+-	O
+values	O
+using	O
+(	O
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+)	O
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+(	O
+note	O
+that	O
+equation	O
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+starts	O
+in	O
+the	O
+Materials	O
+and	O
+Methods	O
+section	O
+)	O
+.	O
+
+Here	O
+,	O
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+the	O
+kth	O
+set	O
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+indices	O
+of	O
+the	O
+i	O
+lists	O
+where	O
+genes	O
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+-	O
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+(	O
+"	O
+success	O
+"	O
+)	O
+.	O
+
+There	O
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+carried	O
+out	O
+accordingly	O
+.	O
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+indices	O
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+N	O
+-	O
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+where	O
+genes	O
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+not	O
+co	O
+-	O
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+(	O
+"	O
+failure	O
+"	O
+)	O
+.	O
+
+[	O
+36	O
+]	O
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+reported	O
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+procedures	O
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+calculating	O
+exact	O
+PBD	O
+P	O
+-	O
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+.	O
+
+However	O
+,	O
+both	O
+procedures	O
+work	O
+with	O
+probability	O
+ratios	O
+and	O
+suffer	O
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+numerical	O
+overflow	O
+/	O
+underflow	O
+problems	O
+for	O
+large	O
+numbers	O
+of	O
+trials	O
+.	O
+
+NetCutter	O
+uses	O
+two	O
+workarounds	O
+to	O
+circumvent	O
+this	O
+problem	O
+.	O
+
+One	O
+is	O
+based	O
+on	O
+using	O
+Poisson	O
+-	O
+binomial	O
+Z	O
+-	O
+scores	O
+,	O
+which	O
+can	O
+be	O
+calculated	O
+very	O
+easily	O
+instead	O
+(	O
+see	O
+below	O
+)	O
+.	O
+
+The	O
+other	O
+relies	O
+on	O
+a	O
+fast	O
+approximation	O
+procedure	O
+for	O
+calculating	O
+Poisson	O
+-	O
+binomial	O
+P	O
+-	O
+values	O
+,	O
+which	O
+we	O
+call	O
+bi	O
+-	O
+binomial	O
+approximation	O
+(	O
+BBA	O
+)	O
+or	O
+bi	O
+-	O
+binomial	O
+distribution	O
+(	O
+BBD	O
+)	O
+.	O
+
+Z	O
+-	O
+scores	O
+and	O
+P	O
+-	O
+values	O
+of	O
+BBD	O
+
+Given	O
+the	O
+mean	O
+mu	O
+(	O
+1	O
+)	O
+and	O
+variance	O
+sigma	O
+2	O
+(	O
+2	O
+)	O
+of	O
+PBD	O
+(	O
+see	O
+Materials	O
+and	O
+Methods	O
+)	O
+,	O
+the	O
+Z	O
+-	O
+score	O
+associated	O
+with	O
+a	O
+given	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+x	O
+is	O
+obtained	O
+as	O
+:	O
+(	O
+19	O
+)	O
+
+Considering	O
+the	O
+structure	O
+of	O
+formulae	O
+(	O
+1	O
+)	O
+and	O
+(	O
+2	O
+)	O
+(	O
+Materials	O
+and	O
+Methods	O
+section	O
+)	O
+,	O
+PBD	O
+Z	O
+-	O
+scores	O
+can	O
+be	O
+calculated	O
+very	O
+easily	O
+and	O
+provide	O
+a	O
+simple	O
+estimate	O
+of	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrence	O
+modules	O
+.	O
+
+However	O
+,	O
+in	O
+contrast	O
+to	O
+normally	O
+distributed	O
+Z	O
+-	O
+scores	O
+,	O
+binomial	O
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+Poisson	O
+-	O
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+Z	O
+-	O
+scores	O
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+not	O
+correspond	O
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+-	O
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+probabilities	O
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+success	O
+.	O
+
+To	O
+see	O
+this	O
+,	O
+calculate	O
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+example	O
+the	O
+probability	O
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+success	O
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+a	O
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+100	O
+Bernoulli	O
+trials	O
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+success	O
+probability	O
+0	O
+.	O
+1	O
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+0	O
+.	O
+9	O
+for	O
+the	O
+expectation	O
+of	O
+10	O
+and	O
+90	O
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+,	O
+respectively	O
+.	O
+
+The	O
+Z	O
+-	O
+score	O
+will	O
+be	O
+0	O
+in	O
+both	O
+cases	O
+but	O
+the	O
+corresponding	O
+cumulative	O
+P	O
+-	O
+values	O
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+0	O
+.	O
+5832	O
+and	O
+0	O
+.	O
+5487	O
+.	O
+
+Therefore	O
+,	O
+exact	O
+levels	O
+of	O
+significance	O
+cannot	O
+be	O
+derived	O
+from	O
+Z	O
+-	O
+scores	O
+alone	O
+.	O
+
+Thus	O
+,	O
+a	O
+fast	O
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+procedure	O
+for	O
+calculating	O
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+-	O
+binomial	O
+P	O
+-	O
+values	O
+is	O
+needed	O
+.	O
+
+The	O
+BBD	O
+approximation	O
+was	O
+developed	O
+to	O
+solve	O
+this	O
+problem	O
+.	O
+
+The	O
+BBD	O
+approximation	O
+of	O
+PBD	O
+P	O
+-	O
+values	O
+follows	O
+from	O
+the	O
+relationship	O
+between	O
+the	O
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+PBD	O
+and	O
+the	O
+population	O
+variance	O
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+trial	O
+-	O
+specific	O
+probabilities	O
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+success	O
+.	O
+
+This	O
+relationship	O
+is	O
+shown	O
+in	O
+Materials	O
+and	O
+Methods	O
+to	O
+be	O
+described	O
+by	O
+(	O
+4	O
+)	O
+:	O
+(	O
+4	O
+)	O
+
+This	O
+equation	O
+shows	O
+that	O
+there	O
+is	O
+an	O
+inverse	O
+linear	O
+relationship	O
+between	O
+the	O
+population	O
+variance	O
+S2	O
+of	O
+the	O
+N	O
+trial	O
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+the	O
+variance	O
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+2	O
+,	O
+which	O
+means	O
+that	O
+PBD	O
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+increasingly	O
+narrow	O
+as	O
+the	O
+variance	O
+of	O
+trial	O
+probabilities	O
+grows	O
+.	O
+
+It	O
+also	O
+shows	O
+that	O
+,	O
+for	O
+constant	O
+mean	O
+mu	O
+and	O
+number	O
+of	O
+trials	O
+N	O
+,	O
+the	O
+shape	O
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+PBD	O
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+only	O
+on	O
+the	O
+variance	O
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+trial	O
+probabilities	O
+.	O
+
+Therefore	O
+,	O
+relationship	O
+(	O
+4	O
+)	O
+suggests	O
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+easy	O
+way	O
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+-	O
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+.	O
+
+The	O
+P	O
+-	O
+value	O
+can	O
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+trial	O
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+trial	O
+probabilities	O
+,	O
+which	O
+,	O
+however	O
+,	O
+are	O
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+.	O
+
+In	O
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+words	O
+,	O
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+Poisson	O
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+Bernoulli	O
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+such	O
+that	O
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+trial	O
+probabilities	O
+.	O
+
+This	O
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+illustrated	O
+in	O
+Fig	O
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+
+4	O
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+why	O
+this	O
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+-	O
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+
+The	O
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+on	O
+how	O
+to	O
+obtain	O
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+Materials	O
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+
+The	O
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+is	O
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+in	O
+supplementary	O
+material	O
+Simulation	O
+S1	O
+.	O
+
+In	O
+order	O
+to	O
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+-	O
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+significance	O
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+-	O
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+an	O
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+uncertainty	O
+coefficient	O
+,	O
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+-	O
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+-	O
+occurrence	O
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+-	O
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+-	O
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+studied	O
+(	O
+Fig	O
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+5	O
+)	O
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+
+Each	O
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+
+Therefore	O
+,	O
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+,	O
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+-	O
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+
+For	O
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+,	O
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+
+The	O
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+-	O
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+For	O
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+-	O
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+,	O
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+the	O
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+
+In	O
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+,	O
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+-	O
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+-	O
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+
+To	O
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+
+These	O
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+
+Three	O
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+
+5	O
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+
+The	O
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+
+This	O
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+,	O
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+,	O
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+
+In	O
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+
+The	O
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+
+When	O
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+
+This	O
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+
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+
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+
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+
+With	O
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+,	O
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+.	O
+
+In	O
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+-	O
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+,	O
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+-	O
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+J	O
+=	O
+0	O
+.	O
+69	O
+and	O
+UC	O
+=	O
+0	O
+.	O
+32	O
+.	O
+
+Taken	O
+together	O
+,	O
+these	O
+data	O
+show	O
+that	O
+the	O
+expected	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+varies	O
+strongly	O
+with	O
+the	O
+level	O
+of	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+and	O
+that	O
+the	O
+expected	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+is	O
+associated	O
+with	O
+different	O
+values	O
+of	O
+UC	O
+and	O
+J	O
+.	O
+
+To	O
+complicate	O
+matters	O
+further	O
+,	O
+66	O
+co	O
+-	O
+occurrences	O
+(	O
+J	O
+=	O
+0	O
+.	O
+49	O
+,	O
+UC	O
+=	O
+0	O
+.	O
+075	O
+)	O
+represent	O
+significant	O
+positive	O
+association	O
+(	O
+PBBD	O
+=	O
+0	O
+.	O
+996	O
+)	O
+with	O
+equal	O
+list	O
+lengths	O
+,	O
+no	O
+significant	O
+association	O
+with	O
+modest	O
+differences	O
+in	O
+list	O
+length	O
+(	O
+PBBD	O
+=	O
+0	O
+.	O
+536	O
+)	O
+and	O
+strongly	O
+negative	O
+association	O
+(	O
+meaning	O
+one	O
+gene	O
+excludes	O
+the	O
+other	O
+)	O
+with	O
+strong	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+(	O
+PBBD	O
+=	O
+0	O
+.	O
+00016	O
+)	O
+.	O
+
+Thus	O
+,	O
+the	O
+same	O
+J	O
+and	O
+UC	O
+association	O
+measure	O
+is	O
+obtained	O
+for	O
+positive	O
+,	O
+negative	O
+,	O
+and	O
+absence	O
+of	O
+association	O
+.	O
+
+Therefore	O
+,	O
+the	O
+meaning	O
+of	O
+these	O
+measures	O
+cannot	O
+be	O
+interpreted	O
+properly	O
+in	O
+the	O
+absence	O
+of	O
+knowledge	O
+about	O
+the	O
+occurrence	O
+probabilities	O
+of	O
+the	O
+co	O
+-	O
+occurring	O
+entities	O
+.	O
+
+Furthermore	O
+,	O
+the	O
+data	O
+in	O
+Fig	O
+.	O
+
+5	O
+also	O
+show	O
+that	O
+neither	O
+J	O
+nor	O
+UC	O
+can	O
+distinguish	O
+between	O
+positive	O
+and	O
+negative	O
+association	O
+while	O
+this	O
+is	O
+easy	O
+with	O
+cumulative	O
+BBD	O
+P	O
+-	O
+values	O
+:	O
+Large	O
+P	O
+-	O
+values	O
+mean	O
+positive	O
+association	O
+and	O
+low	O
+P	O
+-	O
+values	O
+mean	O
+negative	O
+association	O
+.	O
+
+In	O
+summary	O
+,	O
+we	O
+conclude	O
+that	O
+BBD	O
+provides	O
+a	O
+novel	O
+association	O
+measure	O
+that	O
+offers	O
+a	O
+number	O
+of	O
+advantages	O
+over	O
+the	O
+existing	O
+contingency	O
+table	O
+based	O
+association	O
+measures	O
+Jaccard	O
+coefficient	O
+and	O
+uncertainty	O
+coefficient	O
+.	O
+
+The	O
+results	O
+in	O
+Fig	O
+.	O
+
+5	O
+also	O
+show	O
+that	O
+significance	O
+of	O
+association	O
+depends	O
+critically	O
+on	O
+the	O
+specific	O
+distribution	O
+of	O
+co	O
+-	O
+occurring	O
+entities	O
+over	O
+lists	O
+of	O
+varying	O
+length	O
+(	O
+because	O
+this	O
+distribution	O
+determines	O
+the	O
+occurrence	O
+probabilities	O
+)	O
+and	O
+that	O
+contingency	O
+table	O
+based	O
+methods	O
+(	O
+which	O
+cannot	O
+capture	O
+this	O
+distribution	O
+)	O
+should	O
+be	O
+avoided	O
+in	O
+the	O
+presence	O
+of	O
+significant	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+.	O
+
+Generation	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+and	O
+the	O
+identification	O
+of	O
+communities	O
+
+The	O
+procedures	O
+outlined	O
+above	O
+allow	O
+the	O
+identification	O
+of	O
+significant	O
+co	O
+-	O
+occurrence	O
+modules	O
+in	O
+any	O
+type	O
+of	O
+bipartite	O
+graph	O
+.	O
+
+Three	O
+user	O
+defined	O
+parameters	O
+have	O
+an	O
+impact	O
+on	O
+the	O
+stringency	O
+of	O
+co	O
+-	O
+occurrence	O
+analysis	O
+:	O
+The	O
+module	O
+size	O
+,	O
+the	O
+support	O
+,	O
+and	O
+the	O
+Z	O
+-	O
+score	O
+/	O
+P	O
+-	O
+value	O
+cutoff	O
+.	O
+
+The	O
+module	O
+size	O
+determines	O
+how	O
+many	O
+entries	O
+will	O
+be	O
+tested	O
+for	O
+co	O
+-	O
+occurrence	O
+,	O
+the	O
+support	O
+sets	O
+a	O
+lower	O
+boundary	O
+on	O
+the	O
+required	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+,	O
+and	O
+the	O
+Z	O
+-	O
+score	O
+/	O
+P	O
+-	O
+value	O
+cutoff	O
+sets	O
+the	O
+significance	O
+threshold	O
+.	O
+
+In	O
+general	O
+,	O
+higher	O
+module	O
+size	O
+leads	O
+to	O
+more	O
+stringent	O
+co	O
+-	O
+occurrence	O
+analysis	O
+at	O
+the	O
+cost	O
+of	O
+computational	O
+complexity	O
+.	O
+
+The	O
+support	O
+parameter	O
+allows	O
+limiting	O
+this	O
+complexity	O
+by	O
+filtering	O
+out	O
+co	O
+-	O
+occurrence	O
+modules	O
+which	O
+co	O
+-	O
+occur	O
+less	O
+frequently	O
+than	O
+required	O
+by	O
+the	O
+support	O
+.	O
+
+The	O
+significance	O
+cutoff	O
+permits	O
+adjusting	O
+the	O
+signal	O
+-	O
+to	O
+-	O
+noise	O
+ratio	O
+,	O
+which	O
+is	O
+calculated	O
+as	O
+the	O
+number	O
+of	O
+co	O
+-	O
+occurrence	O
+modules	O
+observed	O
+in	O
+the	O
+real	O
+versus	O
+a	O
+randomized	O
+bipartite	O
+graph	O
+.	O
+
+The	O
+impact	O
+of	O
+these	O
+parameters	O
+on	O
+the	O
+stringency	O
+of	O
+co	O
+-	O
+occurrence	O
+analysis	O
+has	O
+been	O
+reported	O
+previously	O
+for	O
+the	O
+PubLiME	O
+data	O
+set	O
+[	O
+35	O
+]	O
+and	O
+is	O
+illustrated	O
+in	O
+a	O
+simulation	O
+study	O
+provided	O
+as	O
+supplementary	O
+material	O
+Simulation	O
+S1	O
+.	O
+
+From	O
+the	O
+set	O
+of	O
+significant	O
+co	O
+-	O
+occurrence	O
+modules	O
+,	O
+a	O
+co	O
+-	O
+occurrence	O
+network	O
+is	O
+generated	O
+by	O
+considering	O
+each	O
+entry	O
+a	O
+vertex	O
+and	O
+drawing	O
+an	O
+edge	O
+between	O
+any	O
+two	O
+vertices	O
+,	O
+which	O
+have	O
+been	O
+part	O
+of	O
+the	O
+same	O
+significant	O
+co	O
+-	O
+occurrence	O
+module	O
+[	O
+35	O
+]	O
+.	O
+
+An	O
+important	O
+question	O
+in	O
+the	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+regards	O
+the	O
+presence	O
+of	O
+network	O
+communities	O
+.	O
+
+Communities	O
+can	O
+be	O
+understood	O
+as	O
+groups	O
+of	O
+vertices	O
+with	O
+the	O
+property	O
+that	O
+the	O
+number	O
+of	O
+edges	O
+running	O
+within	O
+groups	O
+is	O
+larger	O
+than	O
+expected	O
+by	O
+chance	O
+and	O
+that	O
+the	O
+number	O
+of	O
+edges	O
+running	O
+between	O
+groups	O
+is	O
+lower	O
+than	O
+expected	O
+by	O
+chance	O
+[	O
+37	O
+]	O
+.	O
+
+This	O
+problem	O
+of	O
+partitioning	O
+a	O
+graph	O
+is	O
+often	O
+referred	O
+to	O
+as	O
+the	O
+graph	O
+-	O
+cut	O
+problem	O
+(	O
+hence	O
+the	O
+name	O
+NetCutter	O
+)	O
+.	O
+
+NetCutter	O
+is	O
+built	O
+on	O
+the	O
+Java	O
+Universal	O
+Network	O
+and	O
+Graph	O
+framework	O
+(	O
+JUNG	O
+)	O
+software	O
+package	O
+(	O
+http	O
+:	O
+/	O
+/	O
+jung	O
+.	O
+sourceforge	O
+.	O
+net	O
+)	O
+,	O
+which	O
+provides	O
+algorithms	O
+for	O
+solving	O
+this	O
+problem	O
+.	O
+
+In	O
+particular	O
+,	O
+NetCutter	O
+implements	O
+the	O
+Bicomponent	O
+clustering	O
+algorithm	O
+[	O
+38	O
+]	O
+,	O
+the	O
+Edge	O
+-	O
+Betweenness	O
+clustering	O
+algorithm	O
+[	O
+39	O
+]	O
+,	O
+and	O
+the	O
+Exact	O
+Flow	O
+Community	O
+algorithm	O
+[	O
+40	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+there	O
+is	O
+a	O
+clustering	O
+tool	O
+that	O
+is	O
+not	O
+part	O
+of	O
+the	O
+JUNG	O
+package	O
+,	O
+namely	O
+an	O
+algorithm	O
+identifying	O
+communities	O
+using	O
+eigenvectors	O
+of	O
+the	O
+modularity	O
+matrix	O
+[	O
+37	O
+]	O
+.	O
+
+The	O
+code	O
+for	O
+this	O
+algorithm	O
+was	O
+kindly	O
+provided	O
+by	O
+Mark	O
+Newman	O
+in	O
+C	O
++	O
++	O
+and	O
+ported	O
+to	O
+Java	O
+.	O
+
+In	O
+addition	O
+to	O
+these	O
+tools	O
+,	O
+NetCutter	O
+provides	O
+a	O
+number	O
+of	O
+convenience	O
+functions	O
+for	O
+the	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+,	O
+such	O
+as	O
+testing	O
+the	O
+significance	O
+of	O
+lists	O
+reporting	O
+a	O
+set	O
+of	O
+entries	O
+making	O
+up	O
+a	O
+network	O
+community	O
+,	O
+ranking	O
+of	O
+vertices	O
+,	O
+random	O
+graph	O
+generators	O
+for	O
+topological	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+,	O
+and	O
+others	O
+.	O
+
+Details	O
+on	O
+all	O
+functions	O
+are	O
+provided	O
+in	O
+the	O
+NetCutter	O
+software	O
+documentation	O
+.	O
+
+One	O
+of	O
+the	O
+possible	O
+applications	O
+of	O
+NetCutter	O
+is	O
+illustrated	O
+below	O
+.	O
+
+This	O
+application	O
+is	O
+tightly	O
+linked	O
+to	O
+the	O
+bipartite	O
+graph	O
+representation	O
+of	O
+the	O
+data	O
+.	O
+
+Namely	O
+,	O
+NetCutter	O
+can	O
+be	O
+used	O
+to	O
+perform	O
+co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+genes	O
+or	O
+list	O
+derived	O
+from	O
+the	O
+same	O
+bipartite	O
+graph	O
+.	O
+
+The	O
+network	O
+communities	O
+identified	O
+in	O
+each	O
+both	O
+reflect	O
+the	O
+same	O
+underlying	O
+structure	O
+of	O
+the	O
+bipartite	O
+graph	O
+.	O
+
+In	O
+the	O
+case	O
+of	O
+gene	O
+expression	O
+signatures	O
+stored	O
+in	O
+PubLiME	O
+,	O
+clusters	O
+of	O
+genes	O
+correspond	O
+to	O
+clusters	O
+of	O
+publications	O
+,	O
+which	O
+can	O
+reveal	O
+possible	O
+functions	O
+of	O
+gene	O
+clusters	O
+.	O
+
+Cluster	O
+correspondence	O
+and	O
+association	O
+studies	O
+
+The	O
+co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+the	O
+PubLiME	O
+data	O
+set	O
+published	O
+previously	O
+[	O
+35	O
+]	O
+identified	O
+5	O
+major	O
+network	O
+communities	O
+of	O
+genes	O
+with	O
+consistent	O
+functional	O
+annotations	O
+that	O
+are	O
+deregulated	O
+in	O
+cancer	O
+related	O
+gene	O
+expression	O
+signatures	O
+.	O
+
+This	O
+analysis	O
+was	O
+performed	O
+by	O
+considering	O
+all	O
+genes	O
+mentioned	O
+in	O
+a	O
+particular	O
+publication	O
+as	O
+a	O
+single	O
+signature	O
+,	O
+even	O
+though	O
+they	O
+might	O
+have	O
+been	O
+part	O
+of	O
+different	O
+tables	O
+and	O
+cluster	O
+analyses	O
+.	O
+
+Here	O
+we	O
+present	O
+an	O
+advanced	O
+analysis	O
+of	O
+the	O
+PubLiME	O
+data	O
+set	O
+where	O
+each	O
+table	O
+and	O
+/	O
+or	O
+cluster	O
+identified	O
+in	O
+a	O
+given	O
+publication	O
+is	O
+considered	O
+as	O
+a	O
+separate	O
+signature	O
+.	O
+
+This	O
+brings	O
+the	O
+total	O
+number	O
+of	O
+signatures	O
+to	O
+be	O
+analyzed	O
+to	O
+1015	O
+comprising	O
+a	O
+total	O
+of	O
+7358	O
+differentially	O
+regulated	O
+genes	O
+derived	O
+from	O
+233	O
+publications	O
+reporting	O
+cancer	O
+related	O
+signatures	O
+derived	O
+from	O
+human	B
+samples	O
+.	O
+
+We	O
+use	O
+this	O
+analysis	O
+to	O
+illustrate	O
+three	O
+major	O
+points	O
+:	O
+First	O
+,	O
+the	O
+set	O
+of	O
+communities	O
+reported	O
+previously	O
+is	O
+reproduced	O
+by	O
+this	O
+more	O
+fine	O
+-	O
+grained	O
+analysis	O
+.	O
+
+Second	O
+,	O
+the	O
+set	O
+of	O
+gene	O
+communities	O
+corresponds	O
+to	O
+a	O
+set	O
+of	O
+publication	O
+communities	O
+.	O
+
+Third	O
+,	O
+associations	O
+between	O
+publications	O
+and	O
+gene	O
+communities	O
+can	O
+be	O
+calculated	O
+with	O
+higher	O
+stringency	O
+using	O
+the	O
+edge	O
+-	O
+swapping	O
+null	O
+-	O
+model	O
+in	O
+conjunction	O
+with	O
+bi	O
+-	O
+binomial	O
+P	O
+-	O
+values	O
+as	O
+compared	O
+to	O
+binomial	O
+or	O
+hypergeometric	O
+statistics	O
+.	O
+
+The	O
+bipartite	O
+graph	O
+to	O
+be	O
+analyzed	O
+is	O
+composed	O
+of	O
+PubMedID	O
+_	O
+listID	O
+-	O
+gene	O
+pairs	O
+(	O
+see	O
+supplementary	O
+material	O
+Table	O
+S1	O
+)	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+was	O
+carried	O
+out	O
+in	O
+two	O
+ways	O
+:	O
+First	O
+,	O
+gene	O
+co	O
+-	O
+occurrence	O
+was	O
+analyzed	O
+and	O
+communities	O
+of	O
+co	O
+-	O
+occurring	O
+genes	O
+were	O
+defined	O
+by	O
+edge	O
+-	O
+betweenness	O
+clustering	O
+as	O
+described	O
+in	O
+Materials	O
+and	O
+Methods	O
+.	O
+
+Second	O
+,	O
+co	O
+-	O
+occurrence	O
+of	O
+PubMedID	O
+_	O
+listIDs	O
+was	O
+analyzed	O
+.	O
+
+To	O
+this	O
+end	O
+,	O
+the	O
+order	O
+of	O
+PubMedID	O
+_	O
+listID	O
+-	O
+gene	O
+pairs	O
+was	O
+reversed	O
+to	O
+form	O
+GENE	O
+-	O
+PUBMEDID	O
+_	O
+LISTID	O
+pairs	O
+.	O
+
+Thus	O
+,	O
+the	O
+lists	O
+in	O
+the	O
+resulting	O
+bipartite	O
+graph	O
+are	O
+formed	O
+by	O
+genes	O
+and	O
+the	O
+entries	O
+are	O
+the	O
+PubMedID	O
+_	O
+listIDs	O
+where	O
+the	O
+genes	O
+are	O
+reported	O
+as	O
+differentially	O
+regulated	O
+.	O
+
+Occurrence	O
+probabilities	O
+for	O
+the	O
+reversed	O
+bipartite	O
+graph	O
+can	O
+be	O
+obtained	O
+by	O
+transposing	O
+the	O
+occurrence	O
+probability	O
+matrix	O
+of	O
+the	O
+original	O
+bipartite	O
+graph	O
+.	O
+
+Since	O
+the	O
+gene	O
+communities	O
+identified	O
+in	O
+gene	O
+co	O
+-	O
+occurrence	O
+analysis	O
+reflect	O
+the	O
+structure	O
+inherent	O
+in	O
+the	O
+bipartite	O
+graph	O
+(	O
+which	O
+is	O
+not	O
+affected	O
+by	O
+reversing	O
+the	O
+list	O
+-	O
+entry	O
+order	O
+)	O
+,	O
+co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+the	O
+reversed	O
+bipartite	O
+graph	O
+will	O
+result	O
+in	O
+PubMedID	O
+_	O
+listID	O
+communities	O
+that	O
+reflect	O
+the	O
+same	O
+underlying	O
+structure	O
+in	O
+the	O
+bipartite	O
+graph	O
+.	O
+
+In	O
+other	O
+words	O
+,	O
+PubMedID	O
+_	O
+listID	O
+communities	O
+correspond	O
+to	O
+gene	O
+communities	O
+.	O
+
+In	O
+less	O
+abstract	O
+terms	O
+,	O
+the	O
+PubMedID	O
+_	O
+listID	O
+communities	O
+should	O
+correspond	O
+to	O
+sets	O
+of	O
+publications	O
+that	O
+report	O
+similar	O
+sets	O
+of	O
+genes	O
+as	O
+differentially	O
+regulated	O
+.	O
+
+The	O
+identification	O
+of	O
+communities	O
+of	O
+publications	O
+can	O
+help	O
+the	O
+researcher	O
+to	O
+easily	O
+identify	O
+publications	O
+studying	O
+genes	O
+in	O
+a	O
+gene	O
+community	O
+that	O
+is	O
+of	O
+interest	O
+to	O
+the	O
+researcher	O
+.	O
+
+The	O
+results	O
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+both	O
+types	O
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+co	O
+-	O
+occurrence	O
+analysis	O
+are	O
+displayed	O
+in	O
+Fig	O
+.	O
+
+6	O
+.	O
+
+Fig	O
+.	O
+
+6A	O
+shows	O
+the	O
+gene	O
+clusters	O
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+.	O
+
+The	O
+clusters	O
+are	O
+named	O
+after	O
+significant	O
+enrichments	O
+of	O
+gene	O
+categories	O
+as	O
+determined	O
+by	O
+functional	O
+category	O
+enrichment	O
+using	O
+DAVID	O
+[	O
+41	O
+]	O
+.	O
+
+The	O
+P	O
+-	O
+values	O
+shown	O
+are	O
+Benjamini	O
+corrected	O
+for	O
+multiple	O
+testing	O
+as	O
+reported	O
+by	O
+DAVID	O
+.	O
+
+The	O
+clusters	O
+are	O
+very	O
+similar	O
+to	O
+the	O
+clusters	O
+published	O
+previously	O
+[	O
+35	O
+]	O
+.	O
+
+There	O
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+one	O
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+cluster	O
+that	O
+is	O
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+for	O
+ribosomal	O
+proteins	O
+(	O
+"	O
+protein	O
+biosynthesis	O
+"	O
+cluster	O
+)	O
+,	O
+which	O
+has	O
+not	O
+reached	O
+significance	O
+in	O
+our	O
+previous	O
+analysis	O
+.	O
+
+The	O
+"	O
+surface	O
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+"	O
+cluster	O
+contains	O
+many	O
+genes	O
+that	O
+had	O
+been	O
+reported	O
+as	O
+part	O
+of	O
+the	O
+"	O
+signal	O
+transduction	O
+"	O
+cluster	O
+.	O
+
+Altogether	O
+,	O
+however	O
+,	O
+these	O
+results	O
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+support	O
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+notion	O
+that	O
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+gene	O
+clusters	O
+in	O
+the	O
+PubLiME	O
+data	O
+set	O
+can	O
+be	O
+reproduced	O
+by	O
+the	O
+more	O
+fine	O
+-	O
+grained	O
+analysis	O
+that	O
+considers	O
+sublists	O
+in	O
+each	O
+publication	O
+as	O
+separate	O
+signatures	O
+.	O
+
+The	O
+corresponding	O
+clusters	O
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+PubMedID	O
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+in	O
+Fig	O
+.	O
+
+6B	O
+.	O
+
+There	O
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+clusters	O
+,	O
+which	O
+have	O
+been	O
+named	O
+after	O
+their	O
+corresponding	O
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+.	O
+
+Only	O
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+cluster	O
+(	O
+the	O
+"	O
+extracellular	O
+matrix	O
+-	O
+immune	O
+response	O
+cluster	O
+"	O
+)	O
+cannot	O
+be	O
+separated	O
+by	O
+edge	O
+-	O
+betweenness	O
+clustering	O
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+point	O
+of	O
+maximal	O
+graph	O
+modularity	O
+.	O
+
+To	O
+see	O
+that	O
+this	O
+naming	O
+is	O
+indeed	O
+justified	O
+,	O
+we	O
+needed	O
+to	O
+investigate	O
+how	O
+strongly	O
+a	O
+given	O
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+,	O
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+.	O
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+.	O
+how	O
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+in	O
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+genes	O
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+_	O
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+.	O
+
+Binomial	O
+or	O
+hypergemetric	O
+statistics	O
+are	O
+generally	O
+used	O
+to	O
+calculate	O
+this	O
+significance	O
+.	O
+
+However	O
+,	O
+the	O
+bipartite	O
+graph	O
+model	O
+in	O
+conjunction	O
+with	O
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+edge	O
+-	O
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+null	O
+-	O
+model	O
+offers	O
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+-	O
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+approach	O
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+-	O
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+statistics	O
+.	O
+
+The	O
+edge	O
+-	O
+swapping	O
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+-	O
+model	O
+determines	O
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+such	O
+a	O
+way	O
+that	O
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+insignificant	O
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+-	O
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+context	O
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+graph	O
+.	O
+
+However	O
+,	O
+when	O
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+subset	O
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+,	O
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+g	O
+.	O
+all	O
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+genes	O
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+,	O
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+number	O
+of	O
+genes	O
+contained	O
+in	O
+this	O
+list	O
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+significant	O
+according	O
+to	O
+how	O
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+is	O
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+obtain	O
+all	O
+the	O
+genes	O
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+random	O
+draw	O
+from	O
+all	O
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+Thus	O
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+can	O
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+in	O
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+to	O
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+is	O
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+extract	O
+a	O
+subgraph	O
+from	O
+the	O
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+each	O
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+-	O
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+(	O
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+The	O
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+
+From	O
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+
+In	O
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+7	O
+,	O
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+For	O
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+
+The	O
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+
+The	O
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+
+6B	O
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+
+6A	O
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+
+First	O
+,	O
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+=	O
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+)	O
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+
+Second	O
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+
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+
+The	O
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+Table	O
+1	O
+.	O
+
+Negative	O
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+-	O
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+
+It	O
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+,	O
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+-	O
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+,	O
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+.	O
+
+The	O
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+that	O
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+representing	O
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+PubLiME	O
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+.	O
+
+Details	O
+about	O
+all	O
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+lists	O
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+supplementary	O
+material	O
+Table	O
+S2	O
+.	O
+
+Looking	O
+at	O
+these	O
+lists	O
+,	O
+some	O
+general	O
+conclusions	O
+about	O
+the	O
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+clusters	O
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+drawn	O
+.	O
+
+Cell	O
+cycle	O
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+have	O
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+found	O
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+in	O
+a	O
+wide	O
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+of	O
+tumor	O
+types	O
+such	O
+as	O
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+cancer	O
+,	O
+breast	O
+cancer	O
+,	O
+in	O
+biliary	O
+tract	O
+cancer	O
+,	O
+pancreatic	O
+cancer	O
+,	O
+gastric	O
+cancer	O
+,	O
+prostate	O
+cancer	O
+,	O
+T	O
+-	O
+cell	O
+leukemia	O
+,	O
+glioma	O
+,	O
+acute	O
+lymphoblastic	O
+and	O
+myeloblastic	O
+leukemias	O
+,	O
+soft	O
+tissue	O
+sarcoma	O
+,	O
+neuroblastoma	O
+,	O
+as	O
+well	O
+as	O
+in	O
+a	O
+number	O
+of	O
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+model	O
+systems	O
+in	O
+response	O
+to	O
+different	O
+stimuli	O
+.	O
+
+Thus	O
+,	O
+the	O
+cell	O
+cycle	O
+cluster	O
+seems	O
+to	O
+consist	O
+of	O
+genes	O
+with	O
+a	O
+general	O
+role	O
+in	O
+oncogenesis	O
+.	O
+
+The	O
+surface	O
+antigen	O
+cluster	O
+instead	O
+seems	O
+to	O
+be	O
+derived	O
+preferentially	O
+from	O
+studies	O
+on	O
+leukemia	O
+.	O
+
+The	O
+interferon	O
+cluster	O
+genes	O
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+found	O
+deregulated	O
+in	O
+virus	O
+induced	O
+pathologies	O
+such	O
+as	O
+papilloma	O
+virus	O
+induced	O
+cervical	O
+cancer	O
+,	O
+and	O
+viral	O
+hepatitis	O
+.	O
+
+Immune	O
+response	O
+cluster	O
+genes	O
+were	O
+reported	O
+as	O
+differentially	O
+regulated	O
+in	O
+inflammatory	O
+conditions	O
+such	O
+as	O
+ulcerative	O
+colitis	O
+,	O
+Crohn	O
+'	O
+s	O
+disease	O
+,	O
+and	O
+Helicobacter	B
+pylori	I
+infections	O
+.	O
+
+Genes	O
+of	O
+the	O
+extracellular	O
+matrix	O
+cluster	O
+seem	O
+to	O
+be	O
+associated	O
+with	O
+cancer	O
+progression	O
+studies	O
+and	O
+metastatic	O
+potential	O
+.	O
+
+For	O
+the	O
+protein	O
+biosynthesis	O
+cluster	O
+,	O
+there	O
+are	O
+15	O
+signatures	O
+that	O
+are	O
+significantly	O
+enriched	O
+for	O
+those	O
+genes	O
+.	O
+
+The	O
+cancers	O
+studied	O
+comprise	O
+medulloblastoma	O
+,	O
+glioblastoma	O
+,	O
+pancreatic	O
+cancer	O
+,	O
+soft	O
+tissue	O
+sarcoma	O
+,	O
+lung	O
+carcinoma	O
+,	O
+breast	O
+carcinoma	O
+,	O
+prostate	O
+carcinoma	O
+,	O
+multiple	O
+myeloma	O
+,	O
+and	O
+lymphocytic	O
+leukemia	O
+.	O
+
+The	O
+genes	O
+are	O
+also	O
+found	O
+deregulated	O
+in	O
+response	O
+to	O
+DNA	O
+damage	O
+.	O
+
+Although	O
+the	O
+number	O
+of	O
+signatures	O
+is	O
+limited	O
+,	O
+the	O
+variation	O
+in	O
+conditions	O
+where	O
+the	O
+genes	O
+are	O
+deregulated	O
+is	O
+compatible	O
+with	O
+the	O
+hypothesis	O
+that	O
+protein	O
+biosynthesis	O
+genes	O
+,	O
+as	O
+cell	O
+cycle	O
+genes	O
+,	O
+are	O
+deregulated	O
+in	O
+many	O
+cancer	O
+types	O
+,	O
+which	O
+might	O
+reflect	O
+the	O
+general	O
+property	O
+of	O
+cancer	O
+cells	O
+to	O
+divide	O
+and	O
+grow	O
+in	O
+an	O
+uncontrolled	O
+fashion	O
+.	O
+
+Discussion	O
+
+Here	O
+we	O
+have	O
+investigated	O
+basic	O
+aspects	O
+of	O
+co	O
+-	O
+occurrence	O
+analysis	O
+and	O
+present	O
+a	O
+software	O
+tool	O
+,	O
+NetCutter	O
+,	O
+which	O
+can	O
+be	O
+used	O
+to	O
+identify	O
+and	O
+analyze	O
+generic	O
+co	O
+-	O
+occurrence	O
+networks	O
+.	O
+
+In	O
+NetCutter	O
+,	O
+a	O
+co	O
+-	O
+occurrence	O
+data	O
+set	O
+is	O
+represented	O
+as	O
+a	O
+bipartite	O
+graph	O
+with	O
+one	O
+part	O
+representing	O
+lists	O
+and	O
+the	O
+other	O
+part	O
+list	O
+entries	O
+whose	O
+co	O
+-	O
+occurrence	O
+patterns	O
+are	O
+studied	O
+.	O
+
+The	O
+bipartite	O
+graph	O
+representation	O
+of	O
+co	O
+-	O
+occurrence	O
+data	O
+sets	O
+allows	O
+the	O
+efficacy	O
+of	O
+different	O
+null	O
+-	O
+models	O
+to	O
+be	O
+tested	O
+systematically	O
+.	O
+
+We	O
+have	O
+shown	O
+that	O
+an	O
+edge	O
+-	O
+swapping	O
+procedure	O
+used	O
+to	O
+randomize	O
+the	O
+bipartite	O
+graph	O
+generates	O
+a	O
+null	O
+-	O
+model	O
+that	O
+allows	O
+co	O
+-	O
+occurrence	O
+analysis	O
+with	O
+the	O
+highest	O
+stringency	O
+.	O
+
+The	O
+other	O
+null	O
+-	O
+models	O
+tested	O
+here	O
+tend	O
+to	O
+underestimate	O
+occurrence	O
+probabilities	O
+of	O
+entries	O
+per	O
+list	O
+for	O
+lists	O
+and	O
+genes	O
+with	O
+high	O
+vertex	O
+degrees	O
+,	O
+i	O
+.	O
+e	O
+.	O
+for	O
+lists	O
+and	O
+genes	O
+where	O
+most	O
+co	O
+-	O
+occurrences	O
+are	O
+observed	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+co	O
+-	O
+occurrences	O
+are	O
+judged	O
+more	O
+significant	O
+than	O
+they	O
+really	O
+are	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+data	O
+sets	O
+with	O
+exactly	O
+equal	O
+lists	O
+lengths	O
+are	O
+likely	O
+to	O
+be	O
+the	O
+exception	O
+from	O
+the	O
+rule	O
+.	O
+
+It	O
+can	O
+be	O
+assumed	O
+that	O
+some	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+will	O
+be	O
+present	O
+in	O
+most	O
+circumstances	O
+.	O
+
+An	O
+important	O
+consequence	O
+of	O
+list	O
+-	O
+length	O
+-	O
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+regards	O
+the	O
+co	O
+-	O
+occurrence	O
+probability	O
+distribution	O
+used	O
+to	O
+evaluate	O
+the	O
+significance	O
+of	O
+the	O
+observed	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+in	O
+the	O
+presence	O
+of	O
+list	O
+-	O
+length	O
+-	O
+heterogeneity	O
+is	O
+best	O
+performed	O
+using	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+(	O
+a	O
+binomial	O
+distribution	O
+with	O
+trial	O
+specific	O
+probabilities	O
+)	O
+.	O
+
+However	O
+,	O
+calculating	O
+Poisson	O
+-	O
+binomial	O
+P	O
+-	O
+values	O
+for	O
+large	O
+numbers	O
+of	O
+lists	O
+is	O
+difficult	O
+using	O
+existing	O
+procedures	O
+[	O
+36	O
+]	O
+.	O
+
+We	O
+have	O
+presented	O
+an	O
+approximation	O
+to	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+,	O
+called	O
+bi	O
+-	O
+binomial	O
+distribution	O
+,	O
+which	O
+is	O
+based	O
+on	O
+replacing	O
+the	O
+set	O
+of	O
+Poisson	O
+trials	O
+by	O
+two	O
+sets	O
+of	O
+Bernoulli	O
+trials	O
+.	O
+
+The	O
+resulting	O
+distribution	O
+reproduces	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+nearly	O
+exactly	O
+and	O
+its	O
+P	O
+-	O
+values	O
+can	O
+be	O
+calculated	O
+with	O
+ease	O
+even	O
+for	O
+thousands	O
+of	O
+lists	O
+(	O
+see	O
+also	O
+supplementary	O
+material	O
+Simulation	O
+S1	O
+for	O
+details	O
+on	O
+the	O
+precision	O
+of	O
+BBD	O
+)	O
+.	O
+
+Importantly	O
+,	O
+BBD	O
+provides	O
+a	O
+novel	O
+measure	O
+of	O
+association	O
+,	O
+which	O
+is	O
+shown	O
+to	O
+be	O
+superior	O
+to	O
+existing	O
+measures	O
+such	O
+as	O
+the	O
+Jaccard	O
+coefficient	O
+and	O
+the	O
+uncertainty	O
+coefficient	O
+,	O
+whose	O
+values	O
+cannot	O
+be	O
+interpreted	O
+properly	O
+in	O
+the	O
+absence	O
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+knowledge	O
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+occurrence	O
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+co	O
+-	O
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+.	O
+
+It	O
+is	O
+worth	O
+noting	O
+that	O
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+-	O
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+-	O
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+distinguished	O
+from	O
+Gaussian	O
+Z	O
+-	O
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+the	O
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+-	O
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+,	O
+BBDs	O
+,	O
+and	O
+even	O
+BDs	O
+.	O
+
+This	O
+is	O
+because	O
+the	O
+Z	O
+-	O
+score	O
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+part	O
+of	O
+the	O
+function	O
+defining	O
+the	O
+normal	O
+probability	O
+density	O
+while	O
+it	O
+is	O
+not	O
+part	O
+of	O
+the	O
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+of	O
+BD	O
+,	O
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+,	O
+and	O
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+
+As	O
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+consequence	O
+,	O
+the	O
+simple	O
+Poisson	O
+-	O
+binomial	O
+Z	O
+-	O
+score	O
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+approach	O
+to	O
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+co	O
+-	O
+occurrence	O
+must	O
+be	O
+complemented	O
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+the	O
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+Poisson	O
+-	O
+binomial	O
+P	O
+-	O
+values	O
+in	O
+order	O
+to	O
+enable	O
+multiple	O
+testing	O
+corrections	O
+and	O
+to	O
+allow	O
+calculation	O
+of	O
+confidence	O
+levels	O
+in	O
+association	O
+studies	O
+precisely	O
+.	O
+
+However	O
+,	O
+NetCutter	O
+is	O
+equipped	O
+with	O
+a	O
+bipartite	O
+graph	O
+randomization	O
+tool	O
+that	O
+permits	O
+measuring	O
+the	O
+number	O
+of	O
+false	O
+positives	O
+due	O
+to	O
+multiple	O
+testing	O
+directly	O
+by	O
+comparing	O
+the	O
+number	O
+of	O
+significant	O
+co	O
+-	O
+occurrence	O
+modules	O
+in	O
+the	O
+real	O
+bipartite	O
+graph	O
+to	O
+the	O
+corresponding	O
+number	O
+in	O
+a	O
+randomized	O
+version	O
+thereof	O
+.	O
+
+Randomization	O
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+performed	O
+by	O
+edge	O
+-	O
+swapping	O
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+order	O
+to	O
+preserve	O
+vertex	O
+degrees	O
+.	O
+
+The	O
+resulting	O
+signal	O
+-	O
+to	O
+-	O
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+ratios	O
+that	O
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+plotted	O
+for	O
+each	O
+Z	O
+-	O
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+/	O
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+-	O
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+mechanism	O
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+false	O
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+(	O
+see	O
+also	O
+supplementary	O
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+Simulation	O
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+)	O
+.	O
+
+In	O
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+co	O
+-	O
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+,	O
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+-	O
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+-	O
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+been	O
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+
+We	O
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+-	O
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+-	O
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+-	O
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+order	O
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+-	O
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+[	O
+35	O
+]	O
+.	O
+
+In	O
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+,	O
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+-	O
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+by	O
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+,	O
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+.	O
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+.	O
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+each	O
+entry	O
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+each	O
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+.	O
+
+Starting	O
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+,	O
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+-	O
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+size	O
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+-	O
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+-	O
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+
+Given	O
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+-	O
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+-	O
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+,	O
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+-	O
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+-	O
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+
+As	O
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+,	O
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+-	O
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+-	O
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+(	O
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+.	O
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+.	O
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+)	O
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+same	O
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+model	O
+.	O
+
+One	O
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+the	O
+benefits	O
+of	O
+using	O
+higher	O
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+robustness	O
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+the	O
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+in	O
+the	O
+presence	O
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+noise	O
+.	O
+
+This	O
+is	O
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+each	O
+edge	O
+in	O
+the	O
+resulting	O
+co	O
+-	O
+occurrence	O
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+is	O
+evaluated	O
+many	O
+times	O
+since	O
+every	O
+pair	O
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+co	O
+-	O
+occurring	O
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+part	O
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+higher	O
+order	O
+co	O
+-	O
+occurrence	O
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+[	O
+35	O
+]	O
+.	O
+
+Another	O
+advantage	O
+is	O
+that	O
+implicit	O
+relationships	O
+between	O
+entries	O
+,	O
+which	O
+have	O
+never	O
+occurred	O
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+,	O
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+-	O
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+.	O
+
+As	O
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+(	O
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+Simulation	O
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+)	O
+,	O
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+.	O
+
+NetCutter	O
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+lists	O
+reporting	O
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+.	O
+
+In	O
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+case	O
+,	O
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+the	O
+original	O
+bipartite	O
+graph	O
+.	O
+
+The	O
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+communities	O
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+-	O
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+,	O
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+
+NetCutter	O
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+-	O
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+.	O
+
+This	O
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+(	O
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+.	O
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+.	O
+list	O
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+)	O
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+-	O
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+.	O
+
+As	O
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+,	O
+association	O
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+performed	O
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+higher	O
+stringency	O
+.	O
+
+This	O
+result	O
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+examining	O
+the	O
+occurrence	O
+probability	O
+matrix	O
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+is	O
+implicitly	O
+assumed	O
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+or	O
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+the	O
+significance	O
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+overlaps	O
+.	O
+
+In	O
+both	O
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+,	O
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+equal	O
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+present	O
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+.	O
+
+Therefore	O
+,	O
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+success	O
+for	O
+a	O
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+a	O
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+by	O
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+total	O
+number	O
+of	O
+genes	O
+.	O
+
+In	O
+other	O
+words	O
+,	O
+both	O
+tests	O
+are	O
+implicitly	O
+based	O
+on	O
+the	O
+list	O
+vertex	O
+degree	O
+model	O
+,	O
+which	O
+has	O
+been	O
+shown	O
+previously	O
+to	O
+underestimate	O
+the	O
+occurrence	O
+probability	O
+and	O
+the	O
+expected	O
+number	O
+of	O
+co	O
+-	O
+occurrences	O
+for	O
+genes	O
+with	O
+high	O
+vertex	O
+degree	O
+(	O
+see	O
+Fig	O
+.	O
+2A	O
+)	O
+.	O
+
+Since	O
+the	O
+BBD	O
+P	O
+-	O
+values	O
+are	O
+calculated	O
+from	O
+the	O
+ES	O
+-	O
+model	O
+,	O
+which	O
+assigns	O
+higher	O
+occurrence	O
+probabilities	O
+to	O
+genes	O
+with	O
+higher	O
+vertex	O
+degree	O
+and	O
+more	O
+expected	O
+co	O
+-	O
+occurrences	O
+,	O
+the	O
+observed	O
+number	O
+of	O
+overlaps	O
+between	O
+a	O
+set	O
+of	O
+genes	O
+of	O
+interest	O
+and	O
+the	O
+content	O
+of	O
+a	O
+given	O
+list	O
+(	O
+which	O
+can	O
+be	O
+viewed	O
+as	O
+co	O
+-	O
+occurrence	O
+of	O
+the	O
+overlapping	O
+genes	O
+in	O
+that	O
+list	O
+)	O
+will	O
+be	O
+judged	O
+less	O
+significant	O
+when	O
+the	O
+overlapping	O
+genes	O
+are	O
+of	O
+high	O
+vertex	O
+degree	O
+(	O
+and	O
+vice	O
+versa	O
+when	O
+the	O
+overlapping	O
+genes	O
+are	O
+of	O
+low	O
+vertex	O
+degree	O
+)	O
+as	O
+compared	O
+to	O
+binomial	O
+or	O
+hypergeometric	O
+tests	O
+.	O
+
+Since	O
+the	O
+BBD	O
+P	O
+-	O
+values	O
+are	O
+derived	O
+from	O
+the	O
+most	O
+stringent	O
+ES	O
+null	O
+-	O
+model	O
+,	O
+BBD	O
+P	O
+-	O
+values	O
+provide	O
+a	O
+more	O
+reliable	O
+estimate	O
+for	O
+the	O
+significance	O
+of	O
+overlap	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
+of	O
+data	O
+represented	O
+as	O
+bipartite	O
+graphs	O
+permits	O
+visualizing	O
+the	O
+structure	O
+of	O
+the	O
+bipartite	O
+graph	O
+either	O
+as	O
+communities	O
+of	O
+list	O
+entries	O
+(	O
+genes	O
+)	O
+or	O
+as	O
+communities	O
+of	O
+lists	O
+(	O
+PubMedID	O
+_	O
+ListID	O
+)	O
+in	O
+co	O
+-	O
+occurrence	O
+networks	O
+.	O
+
+We	O
+have	O
+analyzed	O
+the	O
+PubLiME	O
+data	O
+set	O
+for	O
+the	O
+presence	O
+of	O
+corresponding	O
+gene	O
+and	O
+list	O
+clusters	O
+.	O
+
+In	O
+addition	O
+to	O
+previously	O
+published	O
+clusters	O
+of	O
+genes	O
+,	O
+we	O
+describe	O
+a	O
+novel	O
+gene	O
+cluster	O
+that	O
+is	O
+composed	O
+of	O
+protein	O
+biosynthesis	O
+associated	O
+genes	O
+[	O
+35	O
+]	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+corresponding	O
+clusters	O
+of	O
+PubMedID	O
+_	O
+ListID	O
+(	O
+gene	O
+expression	O
+signatures	O
+)	O
+are	O
+in	O
+general	O
+strongly	O
+enriched	O
+for	O
+genes	O
+reported	O
+in	O
+the	O
+corresponding	O
+gene	O
+cluster	O
+and	O
+that	O
+interrogation	O
+of	O
+corresponding	O
+clusters	O
+can	O
+be	O
+used	O
+to	O
+deduct	O
+hypotheses	O
+about	O
+the	O
+putative	O
+function	O
+of	O
+gene	O
+clusters	O
+.	O
+
+In	O
+addition	O
+to	O
+co	O
+-	O
+occurrence	O
+analysis	O
+,	O
+NetCutter	O
+offers	O
+a	O
+number	O
+of	O
+tools	O
+for	O
+the	O
+analysis	O
+of	O
+co	O
+-	O
+occurrence	O
+networks	O
+,	O
+or	O
+any	O
+undirected	O
+graph	O
+.	O
+
+In	O
+particular	O
+,	O
+community	O
+identification	O
+is	O
+supported	O
+by	O
+four	O
+different	O
+community	O
+identification	O
+algorithms	O
+.	O
+
+NetCutter	O
+also	O
+offers	O
+a	O
+range	O
+of	O
+convenience	O
+functions	O
+that	O
+are	O
+of	O
+help	O
+in	O
+network	O
+analysis	O
+.	O
+
+Worthy	O
+of	O
+mentioning	O
+are	O
+the	O
+random	O
+graph	O
+generators	O
+that	O
+can	O
+provide	O
+control	O
+graphs	O
+for	O
+topological	O
+studies	O
+.	O
+
+The	O
+complete	O
+set	O
+of	O
+options	O
+is	O
+described	O
+in	O
+the	O
+software	O
+documentation	O
+.	O
+
+In	O
+summary	O
+,	O
+we	O
+present	O
+a	O
+general	O
+framework	O
+for	O
+co	O
+-	O
+occurrence	O
+analysis	O
+with	O
+many	O
+potential	O
+applications	O
+.	O
+
+We	O
+illustrate	O
+a	O
+number	O
+of	O
+advantages	O
+of	O
+using	O
+the	O
+bipartite	O
+graph	O
+representation	O
+of	O
+data	O
+and	O
+the	O
+associated	O
+statistics	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+identification	O
+of	O
+corresponding	O
+clusters	O
+permits	O
+the	O
+identification	O
+of	O
+functional	O
+subunits	O
+such	O
+as	O
+gene	O
+clusters	O
+on	O
+the	O
+one	O
+hand	O
+,	O
+and	O
+the	O
+generation	O
+of	O
+hypotheses	O
+about	O
+the	O
+function	O
+of	O
+those	O
+units	O
+by	O
+analyzing	O
+the	O
+corresponding	O
+list	O
+clusters	O
+on	O
+the	O
+other	O
+hand	O
+.	O
+
+Future	O
+developments	O
+will	O
+be	O
+directed	O
+towards	O
+the	O
+analysis	O
+of	O
+data	O
+sets	O
+that	O
+are	O
+considerably	O
+larger	O
+than	O
+the	O
+data	O
+sets	O
+analyzed	O
+so	O
+far	O
+.	O
+
+For	O
+example	O
+,	O
+co	O
+-	O
+occurrence	O
+analysis	O
+might	O
+be	O
+of	O
+interest	O
+for	O
+the	O
+analysis	O
+of	O
+single	O
+nucleotide	O
+polymorphism	O
+(	O
+SNP	O
+)	O
+data	O
+sets	O
+and	O
+association	O
+studies	O
+of	O
+genome	O
+variability	O
+with	O
+disease	O
+.	O
+
+Each	O
+patient	B
+is	O
+characterized	O
+by	O
+a	O
+specific	O
+range	O
+of	O
+SNPs	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+patterns	O
+of	O
+patients	B
+according	O
+to	O
+their	O
+SNPs	O
+could	O
+be	O
+compared	O
+to	O
+clinical	O
+parameters	O
+with	O
+the	O
+aim	O
+of	O
+identifying	O
+genomic	O
+regions	O
+associated	O
+with	O
+disease	O
+.	O
+
+The	O
+increased	O
+stringency	O
+of	O
+association	O
+studies	O
+offered	O
+by	O
+NetCutter	O
+may	O
+be	O
+of	O
+use	O
+in	O
+the	O
+analysis	O
+of	O
+polygenic	O
+diseases	O
+where	O
+conventional	O
+methods	O
+fail	O
+.	O
+
+For	O
+being	O
+useful	O
+in	O
+this	O
+setting	O
+,	O
+NetCutter	O
+must	O
+be	O
+capable	O
+of	O
+analyzing	O
+bipartite	O
+graphs	O
+with	O
+millions	O
+instead	O
+of	O
+thousands	O
+of	O
+vertices	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Implementation	O
+of	O
+NetCutter	O
+
+NetCutter	O
+is	O
+written	O
+in	O
+Java	O
+using	O
+NetBeans6	O
+software	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+netbeans	O
+.	O
+info	O
+/	O
+)	O
+and	O
+tested	O
+on	O
+the	O
+Java	O
+Runtime	O
+environment	O
+1	O
+.	O
+6	O
+.	O
+0	O
+.	O
+0	O
+.	O
+on	O
+a	O
+Windows	O
+XP	O
+Professional	O
+computer	O
+.	O
+
+The	O
+Java	O
+Runtime	O
+environment	O
+,	O
+which	O
+can	O
+be	O
+downloaded	O
+from	O
+http	O
+:	O
+/	O
+/	O
+java	O
+.	O
+sun	O
+.	O
+com	O
+/	O
+,	O
+must	O
+be	O
+installed	O
+on	O
+a	O
+computer	O
+that	O
+is	O
+intended	O
+to	O
+run	O
+NetCutter	O
+.	O
+
+NetCutter	O
+is	O
+provided	O
+as	O
+a	O
+single	O
+jar	O
+file	O
+and	O
+should	O
+run	O
+by	O
+double	O
+clicking	O
+the	O
+jar	O
+file	O
+,	O
+provided	O
+that	O
+the	O
+Java	O
+runtime	O
+environment	O
+is	O
+properly	O
+installed	O
+.	O
+
+NetCutter	O
+makes	O
+use	O
+of	O
+the	O
+following	O
+software	O
+packages	O
+and	O
+classes	O
+:	O
+JUNG	O
+version	O
+1	O
+.	O
+3	O
+(	O
+http	O
+:	O
+/	O
+/	O
+jung	O
+.	O
+sourceforge	O
+.	O
+net	O
+/	O
+download	O
+.	O
+html	O
+)	O
+,	O
+Apache	O
+Jakarta	O
+Commons	O
+Collections	O
+3	O
+.	O
+1	O
+(	O
+http	O
+:	O
+/	O
+/	O
+jakarta	O
+.	O
+apache	O
+.	O
+org	O
+/	O
+commons	O
+/	O
+collections	O
+/	O
+)	O
+,	O
+Cern	O
+Colt	O
+Scientific	O
+Library	O
+1	O
+.	O
+2	O
+.	O
+0	O
+(	O
+http	O
+:	O
+/	O
+/	O
+dsd	O
+.	O
+lbl	O
+.	O
+gov	O
+/	O
+hoschek	O
+/	O
+colt	O
+/	O
+)	O
+,	O
+Xerces	O
+(	O
+http	O
+:	O
+/	O
+/	O
+xerces	O
+.	O
+apache	O
+.	O
+org	O
+/	O
+xerces2	O
+-	O
+j	O
+/	O
+index	O
+.	O
+html	O
+)	O
+,	O
+Jama	O
+(	O
+http	O
+:	O
+/	O
+/	O
+math	O
+.	O
+nist	O
+.	O
+gov	O
+/	O
+javanumerics	O
+/	O
+jama	O
+/	O
+)	O
+,	O
+Netlib	O
+Java	O
+LAPACK	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+netlib	O
+.	O
+org	O
+/	O
+lapack	O
+/	O
+)	O
+,	O
+JFreeChart	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+jfree	O
+.	O
+org	O
+/	O
+jfreechart	O
+/	O
+)	O
+,	O
+partition	O
+.	O
+java	O
+(	O
+http	O
+:	O
+/	O
+/	O
+astro	O
+.	O
+u	O
+-	O
+strasbg	O
+.	O
+fr	O
+/	O
+fmurtagh	O
+/	O
+mda	O
+-	O
+sw	O
+/	O
+java	O
+/	O
+partition	O
+.	O
+java	O
+)	O
+.	O
+
+Bi	O
+-	O
+binomial	O
+approximation	O
+of	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+
+The	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+(	O
+binomial	O
+distribution	O
+with	O
+trial	O
+specific	O
+probabilities	O
+)	O
+has	O
+recently	O
+been	O
+proposed	O
+as	O
+a	O
+statistic	O
+that	O
+properly	O
+handles	O
+largely	O
+differing	O
+sizes	O
+of	O
+gene	O
+expression	O
+signatures	O
+in	O
+meta	O
+-	O
+analysis	O
+of	O
+gene	O
+expression	O
+data	O
+[	O
+35	O
+]	O
+.	O
+
+Z	O
+-	O
+scores	O
+have	O
+been	O
+used	O
+to	O
+estimate	O
+the	O
+significance	O
+of	O
+co	O
+-	O
+occurrence	O
+because	O
+P	O
+-	O
+value	O
+calculation	O
+is	O
+cumbersome	O
+and	O
+error	O
+prone	O
+.	O
+
+Two	O
+methods	O
+reported	O
+by	O
+[	O
+36	O
+]	O
+suffer	O
+from	O
+numerical	O
+overflow	O
+/	O
+underflow	O
+problems	O
+when	O
+large	O
+numbers	O
+of	O
+Poisson	O
+trials	O
+with	O
+probabilities	O
+deviating	O
+significantly	O
+from	O
+0	O
+.	O
+5	O
+are	O
+being	O
+analyzed	O
+.	O
+
+Therefore	O
+,	O
+we	O
+propose	O
+a	O
+fast	O
+approximation	O
+of	O
+P	O
+-	O
+values	O
+based	O
+on	O
+a	O
+bi	O
+-	O
+binomial	O
+distribution	O
+.	O
+
+The	O
+bi	O
+-	O
+binomial	O
+distribution	O
+is	O
+a	O
+special	O
+case	O
+of	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+where	O
+the	O
+probability	O
+of	O
+success	O
+can	O
+assume	O
+only	O
+two	O
+values	O
+.	O
+
+In	O
+order	O
+to	O
+achieve	O
+a	O
+good	O
+approximation	O
+of	O
+the	O
+underlying	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+,	O
+the	O
+values	O
+of	O
+these	O
+two	O
+probabilities	O
+and	O
+the	O
+number	O
+of	O
+trials	O
+where	O
+they	O
+are	O
+assumed	O
+must	O
+be	O
+determined	O
+carefully	O
+.	O
+
+As	O
+is	O
+shown	O
+in	O
+the	O
+following	O
+,	O
+the	O
+values	O
+of	O
+the	O
+two	O
+trial	O
+probabilities	O
+and	O
+their	O
+number	O
+of	O
+occurrences	O
+follow	O
+from	O
+the	O
+formula	O
+used	O
+to	O
+calculate	O
+the	O
+variance	O
+of	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+and	O
+from	O
+the	O
+formula	O
+yielding	O
+the	O
+population	O
+variance	O
+of	O
+trial	O
+probabilities	O
+of	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+to	O
+be	O
+approximated	O
+.	O
+
+The	O
+mean	O
+mu	O
+and	O
+the	O
+variance	O
+sigma	O
+2	O
+of	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+are	O
+given	O
+by	O
+equation	O
+(	O
+1	O
+)	O
+and	O
+(	O
+2	O
+)	O
+,	O
+respectively	O
+.	O
+(	O
+1	O
+)	O
+(	O
+2	O
+)	O
+pi	O
+is	O
+the	O
+trial	O
+-	O
+specific	O
+probability	O
+of	O
+success	O
+and	O
+N	O
+is	O
+the	O
+total	O
+number	O
+of	O
+trials	O
+.	O
+
+For	O
+the	O
+sake	O
+of	O
+completeness	O
+,	O
+a	O
+formal	O
+proof	O
+of	O
+equation	O
+(	O
+1	O
+)	O
+is	O
+reported	O
+as	O
+supplementary	O
+material	O
+Proof	O
+S1	O
+and	O
+the	O
+proof	O
+of	O
+equation	O
+(	O
+2	O
+)	O
+can	O
+be	O
+obtained	O
+in	O
+an	O
+analogous	O
+fashion	O
+.	O
+
+The	O
+population	O
+variance	O
+S2	O
+of	O
+trial	O
+probabilities	O
+pi	O
+is	O
+given	O
+by	O
+equation	O
+(	O
+3	O
+)	O
+.	O
+(	O
+3	O
+)	O
+
+Rearranging	O
+equation	O
+(	O
+3	O
+)	O
+considering	O
+(	O
+1	O
+)	O
+and	O
+(	O
+2	O
+)	O
+leads	O
+to	O
+(	O
+4	O
+)	O
+and	O
+(	O
+5	O
+)	O
+,	O
+where	O
+pa	O
+denotes	O
+the	O
+average	O
+trial	O
+probability	O
+of	O
+success	O
+and	O
+qa	O
+its	O
+complement	O
+.	O
+(	O
+4	O
+)	O
+(	O
+5	O
+)	O
+Now	O
+let	O
+'	O
+s	O
+define	O
+two	O
+trial	O
+probabilities	O
+p1	O
+and	O
+p2	O
+,	O
+which	O
+are	O
+used	O
+N1	O
+and	O
+N2	O
+times	O
+during	O
+the	O
+Poisson	O
+trials	O
+,	O
+respectively	O
+.	O
+
+Thus	O
+,	O
+N1	O
+and	O
+N2	O
+add	O
+up	O
+to	O
+N	O
+.	O
+(	O
+6	O
+)	O
+
+Considering	O
+(	O
+1	O
+)	O
+,	O
+the	O
+average	O
+trial	O
+probability	O
+pa	O
+can	O
+then	O
+be	O
+obtained	O
+from	O
+(	O
+7	O
+)	O
+.	O
+(	O
+7	O
+)	O
+
+Using	O
+(	O
+7	O
+)	O
+,	O
+p1	O
+can	O
+thus	O
+be	O
+calculated	O
+as	O
+(	O
+8	O
+)	O
+.	O
+(	O
+8	O
+)	O
+
+Similarly	O
+,	O
+considering	O
+(	O
+2	O
+)	O
+,	O
+the	O
+variance	O
+sigma	O
+2	O
+is	O
+given	O
+by	O
+(	O
+9	O
+)	O
+.	O
+(	O
+9	O
+)	O
+
+Substituting	O
+p1	O
+in	O
+(	O
+9	O
+)	O
+using	O
+(	O
+8	O
+)	O
+followed	O
+by	O
+substituting	O
+sigma	O
+2	O
+in	O
+(	O
+5	O
+)	O
+by	O
+(	O
+9	O
+)	O
+leads	O
+to	O
+a	O
+quadratic	O
+equation	O
+for	O
+p2	O
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+a	O
+function	O
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+pa	O
+,	O
+N	O
+,	O
+and	O
+S2	O
+,	O
+as	O
+shown	O
+in	O
+equation	O
+(	O
+10	O
+)	O
+.	O
+(	O
+10	O
+)	O
+
+The	O
+solution	O
+to	O
+(	O
+10	O
+)	O
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+given	O
+by	O
+(	O
+11	O
+)	O
+.	O
+(	O
+11	O
+)	O
+
+Setting	O
+p2	O
+to	O
+(	O
+12	O
+)	O
+p1	O
+can	O
+be	O
+obtained	O
+from	O
+(	O
+8	O
+)	O
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+shown	O
+to	O
+be	O
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+by	O
+formula	O
+(	O
+13	O
+)	O
+:	O
+(	O
+13	O
+)	O
+Choosing	O
+p2	O
+as	O
+(	O
+12a	O
+)	O
+leads	O
+to	O
+p1	O
+(	O
+13a	O
+)	O
+
+Comparing	O
+(	O
+13a	O
+)	O
+to	O
+(	O
+12	O
+)	O
+and	O
+(	O
+12a	O
+)	O
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+(	O
+13	O
+)	O
+,	O
+it	O
+can	O
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+seen	O
+that	O
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+the	O
+fact	O
+that	O
+N1	O
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+N2	O
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+.	O
+
+Since	O
+the	O
+assignment	O
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+set	O
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+trials	O
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+trials	O
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+N2	O
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+arbitrary	O
+,	O
+we	O
+can	O
+limit	O
+the	O
+remaining	O
+analysis	O
+on	O
+(	O
+12	O
+)	O
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+(	O
+13	O
+)	O
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+loss	O
+of	O
+generality	O
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+
+Note	O
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+(	O
+12	O
+)	O
+and	O
+(	O
+13	O
+)	O
+do	O
+not	O
+guarantee	O
+that	O
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+always	O
+confined	O
+between	O
+0	O
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+1	O
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+any	O
+combination	O
+of	O
+N1	O
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+N2	O
+.	O
+
+While	O
+probabilities	O
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+0	O
+or	O
+bigger	O
+than	O
+1	O
+would	O
+still	O
+result	O
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+a	O
+distribution	O
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+same	O
+overall	O
+variance	O
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+distribution	O
+,	O
+P	O
+-	O
+value	O
+calculation	O
+will	O
+be	O
+imprecise	O
+because	O
+the	O
+tails	O
+of	O
+the	O
+distribution	O
+will	O
+deviate	O
+significantly	O
+from	O
+the	O
+original	O
+distribution	O
+.	O
+
+Thus	O
+,	O
+we	O
+need	O
+to	O
+define	O
+the	O
+values	O
+N1	O
+and	O
+N2	O
+in	O
+such	O
+a	O
+way	O
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+<	O
+=	O
+1	O
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+p1	O
+>	O
+=	O
+0	O
+.	O
+
+This	O
+can	O
+be	O
+achieved	O
+by	O
+evaluating	O
+(	O
+12	O
+)	O
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+(	O
+13	O
+)	O
+.	O
+
+Evaluating	O
+(	O
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+)	O
+for	O
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+condition	O
+that	O
+p2	O
+<	O
+=	O
+1	O
+,	O
+solving	O
+the	O
+resulting	O
+inequality	O
+for	O
+N2	O
+,	O
+and	O
+considering	O
+(	O
+5	O
+)	O
+,	O
+which	O
+relates	O
+S2	O
+and	O
+sigma	O
+2	O
+,	O
+we	O
+obtain	O
+(	O
+14	O
+)	O
+.	O
+(	O
+14	O
+)	O
+
+Similarly	O
+,	O
+evaluating	O
+(	O
+13	O
+)	O
+for	O
+the	O
+condition	O
+p1	O
+>	O
+=	O
+0	O
+,	O
+solving	O
+the	O
+resulting	O
+inequality	O
+for	O
+N2	O
+,	O
+considering	O
+(	O
+5	O
+)	O
+,	O
+which	O
+relates	O
+S2	O
+and	O
+sigma	O
+2	O
+,	O
+and	O
+defining	O
+mu	O
+f	O
+the	O
+expected	O
+number	O
+of	O
+failures	O
+as	O
+N	O
+*	O
+(	O
+1	O
+-	O
+pa	O
+)	O
+(	O
+15	O
+)	O
+,	O
+(	O
+15	O
+)	O
+we	O
+obtain	O
+(	O
+16	O
+)	O
+(	O
+16	O
+)	O
+
+The	O
+meaning	O
+of	O
+these	O
+boundaries	O
+is	O
+best	O
+illustrated	O
+by	O
+considering	O
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+Poisson	O
+-	O
+binomial	O
+distribution	O
+whose	O
+variance	O
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+0	O
+,	O
+i	O
+.	O
+e	O
+.	O
+that	O
+assumes	O
+1	O
+at	O
+X	O
+=	O
+mu	O
+and	O
+0	O
+otherwise	O
+.	O
+
+In	O
+this	O
+case	O
+(	O
+14	O
+)	O
+requires	O
+N2	O
+<	O
+=	O
+mu	O
+while	O
+(	O
+16	O
+)	O
+requires	O
+N2	O
+>	O
+=	O
+mu	O
+.	O
+
+These	O
+conditions	O
+can	O
+only	O
+be	O
+fulfilled	O
+contemporaneously	O
+when	O
+N2	O
+is	O
+set	O
+to	O
+mu	O
+.	O
+
+Intuitively	O
+,	O
+this	O
+means	O
+that	O
+there	O
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+success	O
+1	O
+and	O
+N	O
+-	O
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+trials	O
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+probability	O
+of	O
+0	O
+,	O
+resulting	O
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+a	O
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+-	O
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+distribution	O
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+variance	O
+sigma	O
+2	O
+=	O
+0	O
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+mean	O
+mu	O
+.	O
+
+When	O
+sigma	O
+2	O
+is	O
+larger	O
+than	O
+0	O
+,	O
+the	O
+choice	O
+of	O
+N1	O
+and	O
+N2	O
+is	O
+more	O
+flexible	O
+.	O
+
+However	O
+,	O
+since	O
+the	O
+choice	O
+of	O
+N2	O
+=	O
+mu	O
+is	O
+valid	O
+for	O
+all	O
+possible	O
+values	O
+of	O
+sigma	O
+2	O
+,	O
+this	O
+is	O
+how	O
+NetCutter	O
+determines	O
+N1	O
+and	O
+N2	O
+.	O
+
+When	O
+mu	O
+is	O
+not	O
+an	O
+integer	O
+,	O
+N2	O
+is	O
+set	O
+to	O
+the	O
+integer	O
+closest	O
+to	O
+mu	O
+.	O
+
+Having	O
+determined	O
+p2	O
+(	O
+12	O
+)	O
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+p1	O
+(	O
+13	O
+)	O
+as	O
+well	O
+a	O
+N1	O
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+N2	O
+(	O
+14	O
+,	O
+16	O
+,	O
+6	O
+)	O
+,	O
+we	O
+can	O
+now	O
+calculate	O
+the	O
+bi	O
+-	O
+binomial	O
+approximation	O
+of	O
+the	O
+Poisson	O
+-	O
+binomial	O
+distribution	O
+in	O
+a	O
+fashion	O
+that	O
+is	O
+very	O
+similar	O
+to	O
+calculate	O
+the	O
+binomial	O
+P	O
+-	O
+value	O
+.	O
+
+With	O
+q1	O
+=	O
+1	O
+-	O
+p1	O
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+q2	O
+=	O
+1	O
+-	O
+p2	O
+we	O
+obtain	O
+:	O
+(	O
+17	O
+)	O
+
+The	O
+summation	O
+is	O
+necessary	O
+because	O
+i	O
+successes	O
+can	O
+be	O
+obtained	O
+from	O
+any	O
+combination	O
+of	O
+j	O
+p1	O
+and	O
+i	O
+-	O
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+p2	O
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+,	O
+where	O
+j	O
+can	O
+assume	O
+any	O
+value	O
+from	O
+0	O
+to	O
+i	O
+.	O
+
+Calculating	O
+Jaccard	O
+and	O
+uncertainty	O
+coefficients	O
+
+For	O
+the	O
+purpose	O
+of	O
+comparing	O
+the	O
+efficacy	O
+of	O
+the	O
+bi	O
+-	O
+binomial	O
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+as	O
+a	O
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+measure	O
+of	O
+co	O
+-	O
+occurrence	O
+,	O
+Jaccard	O
+and	O
+uncertainty	O
+coefficients	O
+(	O
+which	O
+are	O
+also	O
+called	O
+measures	O
+of	O
+association	O
+)	O
+were	O
+calculated	O
+using	O
+the	O
+formulae	O
+:	O
+
+The	O
+Jaccard	O
+coefficient	O
+J	O
+is	O
+calculated	O
+as	O
+the	O
+number	O
+of	O
+times	O
+A	O
+and	O
+B	O
+occur	O
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+divided	O
+by	O
+the	O
+number	O
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+times	O
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+plus	O
+the	O
+number	O
+of	O
+times	O
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+occurs	O
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+plus	O
+the	O
+number	O
+of	O
+times	O
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+and	O
+B	O
+occur	O
+together	O
+[	O
+42	O
+]	O
+.	O
+
+The	O
+uncertainty	O
+coefficient	O
+[	O
+42	O
+]	O
+is	O
+calculated	O
+as	O
+:	O
+H	O
+is	O
+the	O
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+associated	O
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+,	O
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+,	O
+and	O
+AB	O
+.	O
+
+For	O
+A	O
+,	O
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+n1	O
+out	O
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+lists	O
+(	O
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+/	O
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+)	O
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+n2	O
+out	O
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+lists	O
+(	O
+n2	O
+/	O
+N	O
+)	O
+.	O
+
+Analogous	O
+calculations	O
+lead	O
+to	O
+the	O
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+associated	O
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+.	O
+
+For	O
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+(	O
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+,	O
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+)	O
+,	O
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+,	O
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+,	O
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+,	O
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+neither	O
+A	O
+nor	O
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+occurring	O
+in	O
+the	O
+lists	O
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+used	O
+.	O
+
+Co	O
+-	O
+occurrence	O
+analysis	O
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+the	O
+PubLiME	O
+data	O
+set	O
+
+The	O
+bipartite	O
+graph	O
+to	O
+be	O
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+is	O
+composed	O
+of	O
+27619	O
+PubMedID	O
+_	O
+listID	O
+-	O
+gene	O
+pairs	O
+(	O
+see	O
+supplementary	O
+material	O
+Table	O
+S1	O
+)	O
+.	O
+
+Edge	O
+-	O
+swapping	O
+(	O
+1000	O
+simulations	O
+,	O
+see	O
+above	O
+)	O
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+used	O
+to	O
+determine	O
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+probabilities	O
+and	O
+gene	O
+co	O
+-	O
+occurrence	O
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+using	O
+module	O
+size	O
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+(	O
+co	O
+-	O
+occurrence	O
+of	O
+three	O
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+)	O
+,	O
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+-	O
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+Z	O
+-	O
+score	O
+cutoff	O
+6	O
+,	O
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+-	O
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+-	O
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+1	O
+.	O
+0E	O
+-	O
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+,	O
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+support	O
+5	O
+.	O
+
+Supplementary	O
+material	O
+Simulation	O
+S1	O
+provides	O
+details	O
+on	O
+why	O
+module	O
+size	O
+3	O
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+chosen	O
+.	O
+
+The	O
+support	O
+parameter	O
+ensures	O
+that	O
+each	O
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+-	O
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+-	O
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+present	O
+in	O
+at	O
+least	O
+5	O
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+.	O
+
+We	O
+identified	O
+1654	O
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+in	O
+the	O
+test	O
+data	O
+compared	O
+to	O
+5	O
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+in	O
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+randomized	O
+bipartite	O
+graph	O
+,	O
+corresponding	O
+to	O
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+signal	O
+-	O
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+-	O
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+of	O
+331	O
+.	O
+
+The	O
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+-	O
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+-	O
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+-	O
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+.	O
+
+Gene	O
+communities	O
+were	O
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+-	O
+betweenness	O
+clustering	O
+removing	O
+4	O
+edges	O
+,	O
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+maximal	O
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+modularity	O
+of	O
+0	O
+.	O
+63	O
+.	O
+
+Modularity	O
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+described	O
+by	O
+[	O
+43	O
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+.	O
+
+For	O
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+,	O
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+-	O
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+in	O
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+original	O
+bipartite	O
+graph	O
+were	O
+reversed	O
+to	O
+form	O
+gene	O
+-	O
+PubMedID	O
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+.	O
+
+Occurrence	O
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+original	O
+occurrence	O
+probability	O
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+-	O
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+.	O
+
+PubMedID	O
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+-	O
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+,	O
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+-	O
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+,	O
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+-	O
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+-	O
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+-	O
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+,	O
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+.	O
+
+Please	O
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+of	O
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+parameters	O
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+-	O
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+.	O
+
+The	O
+reversal	O
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+necessitates	O
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+in	O
+gene	O
+co	O
+-	O
+occurrence	O
+analysis	O
+(	O
+5	O
+)	O
+to	O
+be	O
+used	O
+as	O
+module	O
+size	O
+in	O
+PubMedID	O
+_	O
+listID	O
+co	O
+-	O
+occurrence	O
+analysis	O
+and	O
+the	O
+module	O
+size	O
+used	O
+in	O
+gene	O
+co	O
+-	O
+occurrence	O
+analysis	O
+(	O
+3	O
+)	O
+to	O
+be	O
+used	O
+as	O
+the	O
+support	O
+parameter	O
+in	O
+PubMedID	O
+_	O
+listID	O
+co	O
+-	O
+occurrence	O
+analysis	O
+if	O
+the	O
+scope	O
+of	O
+the	O
+analysis	O
+is	O
+the	O
+identification	O
+of	O
+PubMedID	O
+_	O
+listID	O
+clusters	O
+that	O
+correspond	O
+to	O
+gene	O
+clusters	O
+identified	O
+before	O
+.	O
+
+The	O
+significance	O
+cutoffs	O
+remain	O
+unchanged	O
+.	O
+
+PubMedID	O
+_	O
+listID	O
+co	O
+-	O
+occurrence	O
+analysis	O
+revealed	O
+448	O
+significant	O
+co	O
+-	O
+occurrence	O
+modules	O
+in	O
+the	O
+real	O
+bipartite	O
+graph	O
+and	O
+6	O
+significant	O
+co	O
+-	O
+occurrence	O
+modules	O
+in	O
+the	O
+randomized	O
+bipartite	O
+graph	O
+with	O
+a	O
+signal	O
+-	O
+to	O
+-	O
+noise	O
+ratio	O
+of	O
+75	O
+.	O
+
+Communities	O
+in	O
+the	O
+resulting	O
+co	O
+-	O
+occurrence	O
+network	O
+were	O
+identified	O
+by	O
+edge	O
+-	O
+betweenness	O
+clustering	O
+removing	O
+130	O
+edges	O
+.	O
+
+The	O
+resulting	O
+maximal	O
+network	O
+modularity	O
+was	O
+found	O
+to	O
+be	O
+0	O
+.	O
+47	O
+.	O
+
+Supporting	O
+Information	O
+
+Personal	O
+and	O
+environmental	O
+correlates	O
+of	O
+active	O
+travel	O
+and	O
+physical	O
+activity	O
+in	O
+a	O
+deprived	O
+urban	O
+population	O
+
+Abstract	O
+
+Background	O
+
+Environmental	O
+characteristics	O
+may	O
+be	O
+associated	O
+with	O
+patterns	O
+of	O
+physical	O
+activity	O
+in	O
+general	O
+or	O
+with	O
+particular	O
+types	O
+of	O
+physical	O
+activity	O
+such	O
+as	O
+active	O
+travel	O
+(	O
+walking	O
+or	O
+cycling	O
+for	O
+transport	O
+)	O
+.	O
+
+However	O
+,	O
+most	O
+studies	O
+in	O
+this	O
+field	O
+have	O
+been	O
+conducted	O
+in	O
+North	O
+America	O
+and	O
+Australia	O
+,	O
+and	O
+hypotheses	O
+about	O
+putative	O
+correlates	O
+should	O
+be	O
+tested	O
+in	O
+a	O
+wider	O
+range	O
+of	O
+sociospatial	O
+contexts	O
+.	O
+
+We	O
+therefore	O
+examined	O
+the	O
+contribution	O
+of	O
+putative	O
+personal	O
+and	O
+environmental	O
+correlates	O
+of	O
+active	O
+travel	O
+and	O
+overall	O
+physical	O
+activity	O
+in	O
+deprived	O
+urban	O
+neighbourhoods	O
+in	O
+Glasgow	O
+,	O
+Scotland	O
+as	O
+part	O
+of	O
+the	O
+baseline	O
+for	O
+a	O
+longitudinal	O
+study	O
+of	O
+the	O
+effects	O
+of	O
+opening	O
+a	O
+new	O
+urban	O
+motorway	O
+(	O
+freeway	O
+)	O
+.	O
+
+Methods	O
+
+We	O
+conducted	O
+a	O
+postal	O
+survey	O
+of	O
+a	O
+random	O
+sample	O
+of	O
+residents	O
+(	O
+n	O
+=	O
+1322	O
+)	O
+,	O
+collecting	O
+data	O
+on	O
+socioeconomic	O
+status	O
+,	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+,	O
+travel	O
+behaviour	O
+,	O
+physical	O
+activity	O
+and	O
+general	O
+health	O
+and	O
+wellbeing	O
+using	O
+a	O
+new	O
+14	O
+-	O
+item	O
+neighbourhood	O
+rating	O
+scale	O
+,	O
+a	O
+travel	O
+diary	O
+,	O
+the	O
+short	O
+form	O
+of	O
+the	O
+International	O
+Physical	O
+Activity	O
+Questionnaire	O
+(	O
+IPAQ	O
+)	O
+and	O
+the	O
+SF	O
+-	O
+8	O
+.	O
+
+We	O
+analysed	O
+the	O
+correlates	O
+of	O
+active	O
+travel	O
+and	O
+overall	O
+physical	O
+activity	O
+using	O
+multivariate	O
+logistic	O
+regression	O
+,	O
+first	O
+building	O
+models	O
+using	O
+personal	O
+(	O
+individual	O
+and	O
+household	O
+)	O
+explanatory	O
+variables	O
+and	O
+then	O
+adding	O
+environmental	O
+variables	O
+.	O
+
+Results	O
+
+Active	O
+travel	O
+was	O
+associated	O
+with	O
+being	O
+younger	O
+,	O
+living	O
+in	O
+owner	O
+-	O
+occupied	O
+accommodation	O
+,	O
+not	O
+having	O
+to	O
+travel	O
+a	O
+long	O
+distance	O
+to	O
+work	O
+and	O
+not	O
+having	O
+access	O
+to	O
+a	O
+car	O
+,	O
+whereas	O
+overall	O
+physical	O
+activity	O
+was	O
+associated	O
+with	O
+living	O
+in	O
+social	O
+rented	O
+accommodation	O
+and	O
+not	O
+being	O
+overweight	O
+.	O
+
+After	O
+adjusting	O
+for	O
+personal	O
+characteristics	O
+,	O
+neither	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+nor	O
+the	O
+objective	O
+proximity	O
+of	O
+respondents	O
+'	O
+homes	O
+to	O
+motorway	O
+or	O
+major	O
+road	O
+infrastructure	O
+explained	O
+much	O
+of	O
+the	O
+variance	O
+in	O
+active	O
+travel	O
+or	O
+overall	O
+physical	O
+activity	O
+,	O
+although	O
+we	O
+did	O
+identify	O
+a	O
+significant	O
+positive	O
+association	O
+between	O
+active	O
+travel	O
+and	O
+perceived	O
+proximity	O
+to	O
+shops	O
+.	O
+
+Conclusion	O
+
+Apart	O
+from	O
+access	O
+to	O
+local	O
+amenities	O
+,	O
+environmental	O
+characteristics	O
+may	O
+have	O
+limited	O
+influence	O
+on	O
+active	O
+travel	O
+in	O
+deprived	O
+urban	O
+populations	O
+characterised	O
+by	O
+a	O
+low	O
+level	O
+of	O
+car	O
+ownership	O
+,	O
+in	O
+which	O
+people	B
+may	O
+have	O
+less	O
+capacity	O
+for	O
+making	O
+discretionary	O
+travel	O
+choices	O
+than	O
+the	O
+populations	O
+studied	O
+in	O
+most	O
+published	O
+research	O
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+the	O
+environmental	O
+correlates	O
+of	O
+physical	O
+activity	O
+.	O
+
+Background	O
+
+Until	O
+recently	O
+,	O
+research	O
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+correlates	O
+of	O
+physical	O
+activity	O
+was	O
+dominated	O
+by	O
+studies	O
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+individual	O
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+and	O
+psychosocial	O
+characteristics	O
+[	O
+1	O
+]	O
+.	O
+
+This	O
+reflected	O
+an	O
+emphasis	O
+on	O
+promoting	O
+sport	O
+,	O
+recreation	O
+or	O
+health	O
+-	O
+directed	O
+exercise	O
+using	O
+techniques	O
+to	O
+encourage	O
+individual	O
+behaviour	O
+change	O
+[	O
+2	O
+]	O
+.	O
+
+However	O
+,	O
+there	O
+is	O
+little	O
+evidence	O
+that	O
+such	O
+approaches	O
+are	O
+effective	O
+in	O
+increasing	O
+physical	O
+activity	O
+in	O
+the	O
+medium	O
+-	O
+to	O
+-	O
+long	O
+term	O
+[	O
+3	O
+]	O
+.	O
+
+If	O
+habitual	O
+patterns	O
+of	O
+behaviour	O
+are	O
+environmentally	O
+cued	O
+,	O
+sustained	O
+change	O
+is	O
+likely	O
+to	O
+require	O
+a	O
+supportive	O
+environment	O
+in	O
+which	O
+people	B
+can	O
+be	O
+active	O
+[	O
+4	O
+,	O
+5	O
+]	O
+.	O
+
+There	O
+is	O
+therefore	O
+increasing	O
+interest	O
+in	O
+the	O
+influence	O
+of	O
+the	O
+social	O
+and	O
+physical	O
+environment	O
+on	O
+physical	O
+activity	O
+.	O
+
+With	O
+respect	O
+to	O
+the	O
+physical	O
+(	O
+natural	O
+or	O
+built	O
+)	O
+environment	O
+,	O
+a	O
+growing	O
+body	O
+of	O
+evidence	O
+suggests	O
+that	O
+certain	O
+environmental	O
+characteristics	O
+may	O
+be	O
+associated	O
+with	O
+patterns	O
+of	O
+physical	O
+activity	O
+in	O
+general	O
+or	O
+with	O
+particular	O
+types	O
+of	O
+physical	O
+activity	O
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+as	O
+walking	O
+or	O
+cycling	O
+as	O
+modes	O
+of	O
+transport	O
+[	O
+4	O
+-	O
+10	O
+]	O
+.	O
+
+Among	O
+the	O
+correlates	O
+most	O
+frequently	O
+identified	O
+in	O
+such	O
+reviews	O
+-	O
+some	O
+ascertained	O
+using	O
+'	O
+objective	O
+'	O
+measures	O
+,	O
+and	O
+others	O
+in	O
+terms	O
+of	O
+people	B
+'	O
+s	O
+perceptions	O
+-	O
+are	O
+the	O
+aesthetic	O
+quality	O
+of	O
+the	O
+surroundings	O
+,	O
+the	O
+presence	O
+of	O
+pavements	O
+(	O
+sidewalks	O
+)	O
+,	O
+the	O
+convenience	O
+of	O
+facilities	O
+for	O
+being	O
+active	O
+,	O
+the	O
+availability	O
+of	O
+green	O
+space	O
+,	O
+access	O
+to	O
+amenities	O
+(	O
+destinations	O
+)	O
+within	O
+walking	O
+or	O
+cycling	O
+distance	O
+,	O
+safety	O
+from	O
+traffic	O
+and	O
+personal	O
+attack	O
+,	O
+and	O
+the	O
+lack	O
+of	O
+heavy	O
+traffic	O
+.	O
+
+Some	O
+of	O
+these	O
+local	O
+characteristics	O
+reflect	O
+higher	O
+-	O
+order	O
+aspects	O
+of	O
+urban	O
+design	O
+and	O
+spatial	O
+policy	O
+such	O
+as	O
+population	O
+density	O
+,	O
+connectivity	O
+and	O
+mixed	O
+land	O
+use	O
+[	O
+6	O
+,	O
+8	O
+]	O
+.	O
+
+Importantly	O
+,	O
+different	O
+characteristics	O
+may	O
+be	O
+associated	O
+with	O
+different	O
+types	O
+of	O
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+activity	O
+;	O
+for	O
+example	O
+,	O
+Owen	O
+and	O
+colleagues	O
+found	O
+that	O
+the	O
+aesthetic	O
+quality	O
+of	O
+the	O
+surroundings	O
+was	O
+associated	O
+with	O
+walking	O
+for	O
+exercise	O
+or	O
+recreation	O
+and	O
+with	O
+walking	O
+in	O
+general	O
+,	O
+but	O
+not	O
+with	O
+walking	O
+for	O
+transport	O
+,	O
+whereas	O
+perceptions	O
+of	O
+traffic	O
+were	O
+associated	O
+with	O
+walking	O
+for	O
+transport	O
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+walking	O
+in	O
+general	O
+,	O
+but	O
+not	O
+with	O
+walking	O
+for	O
+exercise	O
+or	O
+recreation	O
+[	O
+5	O
+]	O
+.	O
+
+Despite	O
+the	O
+growing	O
+volume	O
+of	O
+published	O
+studies	O
+in	O
+this	O
+field	O
+,	O
+many	O
+authors	O
+remain	O
+circumspect	O
+in	O
+their	O
+interpretation	O
+of	O
+the	O
+available	O
+evidence	O
+.	O
+
+Giles	O
+-	O
+Corti	O
+and	O
+Donovan	O
+have	O
+described	O
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+to	O
+a	O
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+physical	O
+environment	O
+as	O
+a	O
+necessary	O
+,	O
+but	O
+insufficient	O
+,	O
+condition	O
+for	O
+an	O
+increase	O
+in	O
+physical	O
+activity	O
+in	O
+the	O
+population	O
+[	O
+11	O
+]	O
+,	O
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+Handy	O
+found	O
+'	O
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+'	O
+evidence	O
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+an	O
+association	O
+between	O
+physical	O
+activity	O
+and	O
+the	O
+built	O
+environment	O
+in	O
+general	O
+but	O
+'	O
+less	O
+convincing	O
+'	O
+evidence	O
+as	O
+to	O
+which	O
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+environmental	O
+characteristics	O
+were	O
+most	O
+strongly	O
+associated	O
+[	O
+7	O
+]	O
+.	O
+
+One	O
+limitation	O
+of	O
+the	O
+available	O
+evidence	O
+is	O
+that	O
+most	O
+research	O
+has	O
+been	O
+conducted	O
+in	O
+North	O
+America	O
+and	O
+Australia	O
+[	O
+9	O
+,	O
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+]	O
+,	O
+and	O
+it	O
+is	O
+not	O
+clear	O
+whether	O
+associations	O
+observed	O
+in	O
+those	O
+countries	O
+are	O
+generalisable	O
+to	O
+other	O
+settings	O
+with	O
+different	O
+aggregate	O
+socioeconomic	O
+characteristics	O
+(	O
+e	O
+.	O
+g	O
+.	O
+wealth	O
+or	O
+access	O
+to	O
+private	O
+cars	O
+)	O
+or	O
+environmental	O
+characteristics	O
+(	O
+e	O
+.	O
+g	O
+.	O
+climate	O
+,	O
+patterns	O
+of	O
+land	O
+use	O
+,	O
+or	O
+availability	O
+of	O
+public	O
+transport	O
+)	O
+.	O
+
+For	O
+example	O
+,	O
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+American	O
+researchers	O
+are	O
+often	O
+interested	O
+in	O
+the	O
+presence	O
+or	O
+absence	O
+of	O
+pavements	O
+(	O
+sidewalks	O
+)	O
+,	O
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+streets	O
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+(	O
+UK	O
+)	O
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+footpath	O
+beside	O
+them	O
+.	O
+
+Hypotheses	O
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+putative	O
+environmental	O
+correlates	O
+of	O
+physical	O
+activity	O
+therefore	O
+need	O
+to	O
+be	O
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+a	O
+wider	O
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+.	O
+
+A	O
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+limitation	O
+of	O
+the	O
+available	O
+evidence	O
+is	O
+that	O
+identifying	O
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+relationship	O
+between	O
+,	O
+for	O
+example	O
+,	O
+urban	O
+form	O
+and	O
+walking	O
+for	O
+transport	O
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+not	O
+the	O
+same	O
+thing	O
+as	O
+showing	O
+that	O
+changing	O
+the	O
+built	O
+environment	O
+will	O
+lead	O
+to	O
+a	O
+change	O
+in	O
+behaviour	O
+[	O
+13	O
+]	O
+.	O
+
+Few	O
+researchers	O
+have	O
+taken	O
+up	O
+the	O
+opportunity	O
+(	O
+or	O
+challenge	O
+)	O
+presented	O
+by	O
+'	O
+natural	O
+experiments	O
+'	O
+to	O
+investigate	O
+the	O
+effects	O
+of	O
+environmental	O
+interventions	O
+on	O
+physical	O
+activity	O
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+14	O
+]	O
+.	O
+
+We	O
+therefore	O
+established	O
+a	O
+longitudinal	O
+study	O
+to	O
+examine	O
+changes	O
+associated	O
+with	O
+the	O
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+of	O
+a	O
+new	O
+urban	O
+section	O
+of	O
+the	O
+M74	O
+motorway	O
+(	O
+freeway	O
+)	O
+currently	O
+under	O
+construction	O
+in	O
+Glasgow	O
+,	O
+Scotland	O
+.	O
+
+The	O
+rationale	O
+and	O
+design	O
+for	O
+this	O
+study	O
+have	O
+been	O
+described	O
+previously	O
+[	O
+15	O
+]	O
+.	O
+
+It	O
+is	O
+claimed	O
+that	O
+the	O
+new	O
+motorway	O
+,	O
+which	O
+will	O
+mostly	O
+pass	O
+through	O
+or	O
+close	O
+to	O
+densely	O
+-	O
+populated	O
+urban	O
+neighbourhoods	O
+,	O
+will	O
+contribute	O
+to	O
+the	O
+regeneration	O
+of	O
+a	O
+region	O
+which	O
+includes	O
+some	O
+of	O
+the	O
+most	O
+deprived	O
+and	O
+least	O
+healthy	O
+working	O
+-	O
+class	O
+communities	O
+in	O
+Europe	O
+[	O
+16	O
+]	O
+.	O
+
+It	O
+is	O
+also	O
+claimed	O
+that	O
+the	O
+new	O
+motorway	O
+will	O
+divert	O
+traffic	O
+from	O
+local	O
+streets	O
+,	O
+reduce	O
+traffic	O
+noise	O
+and	O
+bring	O
+new	O
+local	O
+employment	O
+opportunities	O
+,	O
+thereby	O
+improving	O
+characteristics	O
+of	O
+the	O
+local	O
+environment	O
+held	O
+to	O
+be	O
+associated	O
+with	O
+active	O
+travel	O
+.	O
+
+Others	O
+claim	O
+that	O
+the	O
+new	O
+motorway	O
+will	O
+encourage	O
+car	O
+use	O
+,	O
+degrade	O
+the	O
+aesthetic	O
+quality	O
+of	O
+the	O
+surroundings	O
+and	O
+reduce	O
+the	O
+safety	O
+and	O
+attractiveness	O
+of	O
+routes	O
+for	O
+pedestrians	O
+and	O
+cyclists	O
+across	O
+the	O
+line	O
+of	O
+the	O
+motorway	O
+-	O
+all	O
+changes	O
+which	O
+may	O
+be	O
+expected	O
+to	O
+discourage	O
+active	O
+travel	O
+[	O
+15	O
+]	O
+.	O
+
+The	O
+eventual	O
+aim	O
+of	O
+the	O
+M74	O
+study	O
+will	O
+be	O
+to	O
+assess	O
+the	O
+effects	O
+of	O
+this	O
+major	O
+modification	O
+to	O
+the	O
+urban	O
+built	O
+environment	O
+and	O
+transport	O
+infrastructure	O
+on	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+and	O
+on	O
+population	O
+health	O
+and	O
+health	O
+-	O
+related	O
+behaviour	O
+,	O
+the	O
+primary	O
+outcome	O
+of	O
+interest	O
+being	O
+a	O
+change	O
+in	O
+the	O
+quantity	O
+of	O
+'	O
+active	O
+travel	O
+'	O
+(	O
+walking	O
+and	O
+cycling	O
+for	O
+transport	O
+)	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+report	O
+findings	O
+from	O
+the	O
+cross	O
+-	O
+sectional	O
+(	O
+baseline	O
+)	O
+phase	O
+of	O
+the	O
+study	O
+which	O
+contribute	O
+evidence	O
+on	O
+the	O
+environmental	O
+correlates	O
+of	O
+physical	O
+activity	O
+in	O
+this	O
+comparatively	O
+deprived	O
+urban	O
+population	O
+.	O
+
+We	O
+focus	O
+on	O
+two	O
+specific	O
+hypotheses	O
+:	O
+first	O
+,	O
+that	O
+levels	O
+of	O
+active	O
+travel	O
+and	O
+overall	O
+physical	O
+activity	O
+vary	O
+with	O
+demographic	O
+and	O
+socioeconomic	O
+characteristics	O
+,	O
+but	O
+not	O
+necessarily	O
+in	O
+the	O
+same	O
+way	O
+;	O
+second	O
+,	O
+that	O
+these	O
+relationships	O
+may	O
+be	O
+partly	O
+explained	O
+by	O
+the	O
+perceived	O
+characteristics	O
+of	O
+the	O
+local	O
+environment	O
+in	O
+which	O
+people	B
+live	O
+and	O
+by	O
+their	O
+objectively	O
+-	O
+assessed	O
+proximity	O
+to	O
+motorway	O
+and	O
+major	O
+road	O
+infrastructure	O
+.	O
+
+Methods	O
+
+Delineation	O
+of	O
+study	O
+areas	O
+
+We	O
+used	O
+spatially	O
+referenced	O
+census	O
+and	O
+transport	O
+infrastructure	O
+data	O
+held	O
+and	O
+analysed	O
+in	O
+a	O
+geographical	O
+information	O
+system	O
+(	O
+GIS	O
+)	O
+,	O
+combined	O
+with	O
+field	O
+visits	O
+,	O
+to	O
+delineate	O
+three	O
+study	O
+areas	O
+in	O
+Glasgow	O
+with	O
+similar	O
+aggregate	O
+socioeconomic	O
+characteristics	O
+and	O
+broadly	O
+similar	O
+topographical	O
+characteristics	O
+apart	O
+from	O
+their	O
+proximity	O
+to	O
+urban	O
+motorway	O
+infrastructure	O
+(	O
+Table	O
+1	O
+,	O
+Figure	O
+1	O
+)	O
+.	O
+
+All	O
+three	O
+study	O
+areas	O
+extended	O
+from	O
+inner	O
+mixed	O
+-	O
+use	O
+districts	O
+close	O
+to	O
+the	O
+city	O
+centre	O
+to	O
+residential	O
+suburbs	O
+,	O
+contained	O
+major	O
+arterial	O
+roads	O
+other	O
+than	O
+motorways	O
+,	O
+and	O
+contained	O
+a	O
+mixture	O
+of	O
+housing	O
+stock	O
+including	O
+traditional	O
+high	O
+-	O
+density	O
+tenements	O
+,	O
+high	O
+-	O
+rise	O
+flats	O
+and	O
+new	O
+housing	O
+developments	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+Sampling	O
+and	O
+survey	O
+administration	O
+
+We	O
+used	O
+the	O
+Royal	O
+Mail	O
+Postcode	O
+Address	O
+File	O
+(	O
+PAF	O
+)	O
+(	O
+version	O
+2005	O
+.	O
+3	O
+)	O
+to	O
+identify	O
+all	O
+residential	O
+addresses	O
+whose	O
+unit	O
+postcode	O
+(	O
+zip	O
+code	O
+)	O
+was	O
+within	O
+one	O
+of	O
+the	O
+study	O
+areas	O
+(	O
+total	O
+n	O
+=	O
+35601	O
+)	O
+and	O
+drew	O
+a	O
+random	O
+sample	O
+of	O
+3000	O
+households	O
+from	O
+each	O
+area	O
+.	O
+
+Unit	O
+postcodes	O
+(	O
+e	O
+.	O
+g	O
+.	O
+G12	O
+8RZ	O
+)	O
+are	O
+the	O
+smallest	O
+available	O
+unit	O
+of	O
+postal	O
+geography	O
+in	O
+the	O
+UK	O
+;	O
+residential	O
+unit	O
+postcodes	O
+cover	O
+about	O
+15	O
+addresses	O
+on	O
+average	O
+.	O
+
+We	O
+sent	O
+the	O
+survey	O
+to	O
+all	O
+households	O
+(	O
+total	O
+n	O
+=	O
+9000	O
+)	O
+between	O
+28	O
+September	O
+and	O
+4	O
+October	O
+2005	O
+and	O
+resent	O
+the	O
+survey	O
+to	O
+all	O
+non	O
+-	O
+responding	O
+households	O
+between	O
+26	O
+and	O
+31	O
+October	O
+2005	O
+.	O
+
+We	O
+alerted	O
+households	O
+to	O
+the	O
+survey	O
+by	O
+means	O
+of	O
+a	O
+postcard	O
+sent	O
+a	O
+few	O
+days	O
+in	O
+advance	O
+,	O
+used	O
+coloured	O
+paper	O
+for	O
+some	O
+of	O
+the	O
+survey	O
+materials	O
+,	O
+and	O
+posted	O
+survey	O
+packs	O
+in	O
+white	O
+envelopes	O
+printed	O
+with	O
+the	O
+university	O
+crest	O
+;	O
+these	O
+techniques	O
+have	O
+been	O
+shown	O
+in	O
+a	O
+meta	O
+-	O
+analysis	O
+to	O
+be	O
+associated	O
+with	O
+increased	O
+response	O
+rates	O
+to	O
+postal	O
+surveys	O
+[	O
+17	O
+]	O
+.	O
+
+We	O
+asked	O
+householders	O
+to	O
+ensure	O
+that	O
+the	O
+questionnaire	O
+was	O
+completed	O
+by	O
+a	O
+resident	O
+aged	O
+16	O
+or	O
+over	O
+;	O
+if	O
+more	O
+than	O
+one	O
+resident	O
+was	O
+eligible	O
+,	O
+we	O
+asked	O
+householders	O
+to	O
+select	O
+the	O
+person	B
+with	O
+the	O
+most	O
+recent	O
+birthday	O
+.	O
+
+Respondents	O
+who	O
+consented	O
+to	O
+follow	O
+-	O
+up	O
+were	O
+entered	O
+into	O
+a	O
+prize	O
+draw	O
+to	O
+win	O
+a	O
+pound	O
+50	O
+(	O
+euro	O
+63	O
+;	O
+US	O
+$	O
+92	O
+)	O
+gift	O
+voucher	O
+.	O
+
+Responses	O
+received	O
+more	O
+than	O
+three	O
+months	O
+after	O
+the	O
+first	O
+mailing	O
+wave	O
+were	O
+disregarded	O
+in	O
+analysis	O
+.	O
+
+Data	O
+collection	O
+
+The	O
+questionnaire	O
+included	O
+items	O
+on	O
+demographic	O
+and	O
+socioeconomic	O
+characteristics	O
+,	O
+health	O
+and	O
+wellbeing	O
+(	O
+including	O
+the	O
+the	O
+SF	O
+-	O
+8	O
+scale	O
+)	O
+,	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+,	O
+travel	O
+behaviour	O
+and	O
+the	O
+short	O
+form	O
+of	O
+the	O
+International	O
+Physical	O
+Activity	O
+Questionnaire	O
+(	O
+IPAQ	O
+)	O
+(	O
+Additional	O
+file	O
+1	O
+)	O
+.	O
+
+We	O
+developed	O
+a	O
+new	O
+'	O
+neighbourhood	O
+scale	O
+'	O
+to	O
+assess	O
+perceptions	O
+of	O
+relevant	O
+characteristics	O
+of	O
+the	O
+local	O
+environment	O
+(	O
+aesthetics	O
+,	O
+green	O
+space	O
+,	O
+access	O
+to	O
+amenities	O
+,	O
+convenience	O
+of	O
+routes	O
+,	O
+traffic	O
+,	O
+road	O
+safety	O
+and	O
+personal	O
+safety	O
+)	O
+.	O
+
+The	O
+development	O
+,	O
+principal	O
+components	O
+analysis	O
+and	O
+reliability	O
+of	O
+the	O
+items	O
+in	O
+this	O
+scale	O
+and	O
+the	O
+derivation	O
+and	O
+reliability	O
+of	O
+summary	O
+variables	O
+are	O
+reported	O
+in	O
+an	O
+accompanying	O
+paper	O
+[	O
+18	O
+]	O
+.	O
+
+Data	O
+cleaning	O
+and	O
+derivation	O
+of	O
+variables	O
+
+Demographic	O
+and	O
+socioeconomic	O
+characteristics	O
+
+We	O
+excluded	O
+from	O
+analysis	O
+all	O
+respondents	O
+who	O
+failed	O
+to	O
+enter	O
+their	O
+age	O
+or	O
+sex	O
+.	O
+
+We	O
+then	O
+examined	O
+the	O
+distributions	O
+of	O
+all	O
+raw	O
+variables	O
+and	O
+carried	O
+out	O
+range	O
+and	O
+consistency	O
+checks	O
+to	O
+identify	O
+any	O
+anomalous	O
+values	O
+or	O
+variables	O
+with	O
+a	O
+high	O
+proportion	O
+of	O
+missing	O
+responses	O
+.	O
+
+As	O
+a	O
+consequence	O
+,	O
+we	O
+collapsed	O
+responses	O
+on	O
+distance	O
+to	O
+place	O
+of	O
+work	O
+or	O
+study	O
+,	O
+housing	O
+tenure	O
+,	O
+car	O
+access	O
+and	O
+working	O
+situation	O
+into	O
+fewer	O
+categories	O
+by	O
+merging	O
+categories	O
+with	O
+small	O
+numbers	O
+of	O
+responses	O
+;	O
+we	O
+also	O
+disregarded	O
+household	O
+composition	O
+and	O
+working	O
+situation	O
+of	O
+spouse	O
+or	O
+partner	O
+in	O
+analysis	O
+because	O
+of	O
+the	O
+large	O
+numbers	O
+of	O
+missing	O
+values	O
+for	O
+these	O
+variables	O
+.	O
+
+Health	O
+and	O
+wellbeing	O
+
+We	O
+calculated	O
+body	O
+mass	O
+index	O
+(	O
+BMI	O
+)	O
+by	O
+converting	O
+,	O
+where	O
+necessary	O
+,	O
+self	O
+-	O
+reported	O
+heights	O
+and	O
+weights	O
+from	O
+imperial	O
+to	O
+metric	O
+units	O
+and	O
+dividing	O
+the	O
+height	O
+in	O
+metres	O
+by	O
+the	O
+square	O
+of	O
+the	O
+weight	O
+in	O
+kilograms	O
+;	O
+we	O
+also	O
+categorised	O
+respondents	O
+into	O
+quintiles	O
+of	O
+BMI	O
+.	O
+
+We	O
+calculated	O
+physical	O
+(	O
+PCS	O
+-	O
+8	O
+)	O
+and	O
+mental	O
+(	O
+MCS	O
+-	O
+8	O
+)	O
+health	O
+summary	O
+scores	O
+from	O
+the	O
+SF	O
+-	O
+8	O
+data	O
+and	O
+scaled	O
+these	O
+to	O
+population	O
+norms	O
+using	O
+the	O
+method	O
+and	O
+coefficients	O
+given	O
+in	O
+the	O
+SF	O
+-	O
+8	O
+manual	O
+[	O
+19	O
+]	O
+.	O
+
+Objective	O
+environmental	O
+characteristics	O
+
+We	O
+linked	O
+each	O
+record	O
+to	O
+the	O
+unit	O
+postcode	O
+of	O
+residence	O
+.	O
+
+We	O
+then	O
+constructed	O
+concentric	O
+buffers	O
+at	O
+100	O
+-	O
+metre	O
+intervals	O
+up	O
+to	O
+500	O
+metres	O
+around	O
+the	O
+routes	O
+and	O
+access	O
+points	O
+of	O
+existing	O
+and	O
+planned	O
+motorways	O
+and	O
+around	O
+the	O
+network	O
+of	O
+other	O
+major	O
+(	O
+A	O
+-	O
+and	O
+B	O
+-	O
+class	O
+)	O
+roads	O
+,	O
+and	O
+assigned	O
+each	O
+respondent	O
+to	O
+a	O
+category	O
+of	O
+proximity	O
+to	O
+each	O
+type	O
+of	O
+road	O
+infrastructure	O
+(	O
+within	O
+100	O
+metres	O
+,	O
+101	O
+-	O
+200	O
+metres	O
+,	O
+etc	O
+.	O
+)	O
+based	O
+on	O
+the	O
+location	O
+of	O
+the	O
+centroid	O
+of	O
+their	O
+unit	O
+postcode	O
+.	O
+
+Travel	O
+behaviour	O
+
+For	O
+travel	O
+time	O
+analysis	O
+we	O
+included	O
+travel	O
+diaries	O
+which	O
+recorded	O
+no	O
+travel	O
+at	O
+all	O
+,	O
+but	O
+we	O
+disregarded	O
+travel	O
+data	O
+from	O
+respondents	O
+who	O
+had	O
+not	O
+been	O
+at	O
+home	O
+on	O
+the	O
+day	O
+of	O
+the	O
+travel	O
+diary	O
+,	O
+whose	O
+questionnaire	O
+had	O
+been	O
+misprinted	O
+such	O
+that	O
+the	O
+travel	O
+diary	O
+pages	O
+were	O
+unusable	O
+,	O
+who	O
+had	O
+recorded	O
+journeys	O
+without	O
+reporting	O
+valid	O
+quantitative	O
+data	O
+on	O
+the	O
+durations	O
+of	O
+those	O
+journeys	O
+,	O
+or	O
+whose	O
+completed	O
+travel	O
+diary	O
+appeared	O
+implausible	O
+.	O
+
+We	O
+also	O
+disregarded	O
+journeys	O
+whose	O
+purpose	O
+was	O
+not	O
+stated	O
+or	O
+was	O
+beyond	O
+the	O
+scope	O
+of	O
+the	O
+travel	O
+diary	O
+(	O
+Additional	O
+file	O
+1	O
+,	O
+page	O
+8	O
+)	O
+.	O
+
+We	O
+summed	O
+the	O
+reported	O
+travel	O
+time	O
+for	O
+each	O
+mode	O
+of	O
+transport	O
+,	O
+calculated	O
+a	O
+total	O
+travel	O
+time	O
+by	O
+active	O
+modes	O
+(	O
+walking	O
+plus	O
+cycling	O
+)	O
+and	O
+by	O
+all	O
+modes	O
+combined	O
+,	O
+and	O
+calculated	O
+the	O
+proportion	O
+of	O
+total	O
+travel	O
+time	O
+contributed	O
+by	O
+each	O
+mode	O
+of	O
+transport	O
+.	O
+
+Physical	O
+activity	O
+
+We	O
+cleaned	O
+and	O
+analysed	O
+IPAQ	O
+data	O
+in	O
+accordance	O
+with	O
+the	O
+IPAQ	O
+scoring	O
+protocol	O
+.	O
+
+We	O
+therefore	O
+disregarded	O
+physical	O
+activity	O
+data	O
+from	O
+respondents	O
+who	O
+had	O
+reported	O
+more	O
+than	O
+16	O
+hours	O
+of	O
+physical	O
+activity	O
+per	O
+day	O
+or	O
+who	O
+had	O
+missing	O
+or	O
+internally	O
+inconsistent	O
+data	O
+on	O
+the	O
+frequency	O
+or	O
+duration	O
+of	O
+any	O
+of	O
+the	O
+three	O
+categories	O
+of	O
+physical	O
+activity	O
+(	O
+walking	O
+,	O
+moderate	O
+-	O
+intensity	O
+activity	O
+or	O
+vigorous	O
+activity	O
+)	O
+.	O
+
+We	O
+also	O
+recoded	O
+reported	O
+durations	O
+of	O
+activity	O
+of	O
+less	O
+than	O
+ten	O
+minutes	O
+to	O
+zero	O
+,	O
+and	O
+of	O
+greater	O
+than	O
+180	O
+minutes	O
+to	O
+180	O
+minutes	O
+.	O
+
+We	O
+calculated	O
+the	O
+estimated	O
+total	O
+physical	O
+activity	O
+energy	O
+expenditure	O
+for	O
+each	O
+respondent	O
+(	O
+MET	O
+-	O
+min	O
+/	O
+week	O
+)	O
+and	O
+used	O
+a	O
+combination	O
+of	O
+frequency	O
+,	O
+duration	O
+and	O
+total	O
+energy	O
+expenditure	O
+to	O
+assign	O
+each	O
+respondent	O
+to	O
+a	O
+'	O
+high	O
+'	O
+,	O
+'	O
+moderate	O
+'	O
+or	O
+'	O
+low	O
+'	O
+category	O
+of	O
+overall	O
+physical	O
+activity	O
+in	O
+accordance	O
+with	O
+the	O
+prescribed	O
+IPAQ	O
+algorithm	O
+.	O
+
+The	O
+'	O
+high	O
+'	O
+category	O
+corresponds	O
+to	O
+a	O
+sufficient	O
+level	O
+of	O
+physical	O
+activity	O
+to	O
+meet	O
+current	O
+public	O
+health	O
+recommendations	O
+for	O
+adults	O
+[	O
+20	O
+]	O
+.	O
+
+Analysis	O
+
+We	O
+considered	O
+it	O
+unlikely	O
+that	O
+the	O
+statistical	O
+assumptions	O
+required	O
+for	O
+linear	O
+regression	O
+could	O
+be	O
+met	O
+because	O
+the	O
+distributions	O
+of	O
+time	O
+spent	O
+walking	O
+and	O
+cycling	O
+and	O
+of	O
+estimated	O
+total	O
+physical	O
+activity	O
+energy	O
+expenditure	O
+were	O
+both	O
+strongly	O
+positively	O
+skewed	O
+and	O
+dominated	O
+by	O
+a	O
+large	O
+number	O
+of	O
+zero	O
+values	O
+which	O
+meant	O
+that	O
+the	O
+data	O
+were	O
+not	O
+amenable	O
+to	O
+log	O
+-	O
+transformation	O
+.	O
+
+We	O
+therefore	O
+modelled	O
+the	O
+correlates	O
+of	O
+active	O
+travel	O
+and	O
+physical	O
+activity	O
+using	O
+multivariate	O
+logistic	O
+regression	O
+.	O
+
+We	O
+defined	O
+'	O
+active	O
+travel	O
+'	O
+as	O
+a	O
+binary	O
+condition	O
+achieved	O
+by	O
+any	O
+respondent	O
+who	O
+had	O
+reported	O
+at	O
+least	O
+30	O
+minutes	O
+of	O
+travel	O
+by	O
+walking	O
+,	O
+cycling	O
+or	O
+both	O
+in	O
+their	O
+travel	O
+diary	O
+,	O
+reflecting	O
+the	O
+current	O
+recommendation	O
+that	O
+adults	O
+should	O
+accumulate	O
+at	O
+least	O
+30	O
+minutes	O
+of	O
+moderate	O
+-	O
+intensity	O
+physical	O
+activity	O
+on	O
+most	O
+days	O
+of	O
+the	O
+week	O
+[	O
+20	O
+]	O
+,	O
+and	O
+we	O
+defined	O
+'	O
+physical	O
+activity	O
+'	O
+as	O
+a	O
+binary	O
+condition	O
+achieved	O
+by	O
+any	O
+respondent	O
+whose	O
+overall	O
+physical	O
+activity	O
+was	O
+categorised	O
+as	O
+'	O
+high	O
+'	O
+using	O
+IPAQ	O
+.	O
+
+We	O
+then	O
+built	O
+separate	O
+multivariate	O
+models	O
+for	O
+active	O
+travel	O
+and	O
+physical	O
+activity	O
+following	O
+the	O
+method	O
+of	O
+Hosmer	O
+and	O
+Lemeshow	O
+[	O
+21	O
+]	O
+,	O
+first	O
+including	O
+only	O
+'	O
+personal	O
+'	O
+(	O
+individual	O
+or	O
+household	O
+)	O
+variables	O
+and	O
+then	O
+adding	O
+'	O
+environmental	O
+'	O
+variables	O
+(	O
+Additional	O
+file	O
+2	O
+)	O
+.	O
+
+Results	O
+
+Response	O
+
+We	O
+received	O
+1345	O
+completed	O
+questionnaires	O
+.	O
+
+After	O
+subtracting	O
+from	O
+the	O
+numerator	O
+23	O
+completed	O
+questionnaires	O
+with	O
+missing	O
+critical	O
+demographic	O
+data	O
+(	O
+age	O
+or	O
+sex	O
+)	O
+,	O
+and	O
+after	O
+subtracting	O
+from	O
+the	O
+denominator	O
+676	O
+addresses	O
+from	O
+which	O
+survey	O
+packs	O
+were	O
+returned	O
+as	O
+undeliverable	O
+,	O
+this	O
+left	O
+1322	O
+valid	O
+responses	O
+to	O
+be	O
+entered	O
+into	O
+analysis	O
+-	O
+a	O
+response	O
+rate	O
+of	O
+1322	O
+/	O
+(	O
+9000	O
+-	O
+676	O
+)	O
+=	O
+15	O
+.	O
+9	O
+%	O
+.	O
+
+Characteristics	O
+of	O
+study	O
+participants	B
+
+Demographic	O
+and	O
+socioeconomic	O
+characteristics	O
+
+Respondents	O
+were	O
+aged	O
+between	O
+16	O
+and	O
+89	O
+years	O
+(	O
+median	O
+age	O
+48	O
+years	O
+)	O
+.	O
+
+804	O
+(	O
+61	O
+%	O
+)	O
+were	O
+women	B
+.	O
+
+Only	O
+136	O
+(	O
+26	O
+%	O
+)	O
+of	O
+the	O
+men	B
+and	O
+145	O
+(	O
+18	O
+%	O
+)	O
+of	O
+the	O
+women	B
+reported	O
+having	O
+access	O
+to	O
+a	O
+bicycle	O
+.	O
+
+For	O
+those	O
+who	O
+usually	O
+travelled	O
+to	O
+a	O
+place	O
+of	O
+work	O
+or	O
+study	O
+,	O
+the	O
+median	O
+reported	O
+distance	O
+was	O
+3	O
+.	O
+5	O
+miles	O
+(	O
+about	O
+5	O
+.	O
+5	O
+kilometres	O
+)	O
+.	O
+
+Other	O
+characteristics	O
+of	O
+study	O
+participants	B
+are	O
+summarised	O
+in	O
+Table	O
+2	O
+.	O
+
+Health	O
+and	O
+wellbeing	O
+
+25	O
+%	O
+of	O
+respondents	O
+reported	O
+difficulty	O
+walking	O
+for	O
+a	O
+quarter	O
+of	O
+a	O
+mile	O
+,	O
+39	O
+%	O
+reported	O
+a	O
+long	O
+-	O
+term	O
+health	O
+problem	O
+or	O
+disability	O
+,	O
+and	O
+50	O
+%	O
+were	O
+overweight	O
+(	O
+median	O
+BMI	O
+25	O
+.	O
+1	O
+kg	O
+/	O
+m2	O
+)	O
+.	O
+
+The	O
+median	O
+mental	O
+health	O
+summary	O
+score	O
+(	O
+MCS	O
+-	O
+8	O
+)	O
+was	O
+significantly	O
+lower	O
+(	O
+i	O
+.	O
+e	O
+.	O
+poorer	O
+)	O
+than	O
+the	O
+population	O
+norm	O
+(	O
+median	O
+47	O
+.	O
+3	O
+,	O
+95	O
+%	O
+CI	O
+46	O
+.	O
+4	O
+to	O
+48	O
+.	O
+1	O
+)	O
+;	O
+the	O
+median	O
+physical	O
+health	O
+summary	O
+score	O
+(	O
+PCS	O
+-	O
+8	O
+)	O
+was	O
+not	O
+significantly	O
+different	O
+from	O
+the	O
+population	O
+norm	O
+(	O
+median	O
+50	O
+.	O
+9	O
+,	O
+95	O
+%	O
+CI	O
+49	O
+.	O
+6	O
+to	O
+51	O
+.	O
+7	O
+)	O
+.	O
+
+Descriptive	O
+data	O
+on	O
+travel	O
+behaviour	O
+and	O
+physical	O
+activity	O
+
+Travel	O
+behaviour	O
+
+1099	O
+travel	O
+diaries	O
+were	O
+suitable	O
+for	O
+travel	O
+time	O
+analysis	O
+.	O
+
+Men	B
+and	O
+women	B
+were	O
+equally	O
+likely	O
+to	O
+have	O
+returned	O
+usable	O
+travel	O
+time	O
+data	O
+,	O
+but	O
+respondents	O
+who	O
+were	O
+older	O
+,	O
+retired	O
+,	O
+or	O
+living	O
+in	O
+social	O
+rented	O
+accommodation	O
+or	O
+who	O
+did	O
+not	O
+have	O
+access	O
+to	O
+a	O
+car	O
+were	O
+less	O
+likely	O
+to	O
+have	O
+returned	O
+usable	O
+data	O
+.	O
+
+On	O
+average	O
+,	O
+respondents	O
+recorded	O
+about	O
+an	O
+hour	O
+'	O
+s	O
+travel	O
+per	O
+day	O
+(	O
+mean	O
+61	O
+.	O
+5	O
+minutes	O
+,	O
+median	O
+50	O
+.	O
+0	O
+minutes	O
+)	O
+,	O
+of	O
+which	O
+a	O
+minority	O
+was	O
+spent	O
+using	O
+active	O
+modes	O
+of	O
+transport	O
+(	O
+walking	O
+or	O
+cycling	O
+:	O
+mean	O
+20	O
+.	O
+0	O
+minutes	O
+,	O
+median	O
+10	O
+.	O
+0	O
+minutes	O
+)	O
+(	O
+Table	O
+3	O
+)	O
+.	O
+
+304	O
+respondents	O
+(	O
+28	O
+%	O
+)	O
+recorded	O
+at	O
+least	O
+30	O
+minutes	O
+of	O
+active	O
+travel	O
+,	O
+of	O
+whom	O
+294	O
+(	O
+97	O
+%	O
+)	O
+recorded	O
+at	O
+least	O
+30	O
+minutes	O
+of	O
+walking	O
+.	O
+
+Physical	O
+activity	O
+
+833	O
+respondents	O
+returned	O
+complete	O
+physical	O
+activity	O
+data	O
+suitable	O
+for	O
+analysis	O
+.	O
+
+Women	B
+and	O
+respondents	O
+who	O
+were	O
+older	O
+,	O
+retired	O
+,	O
+or	O
+living	O
+in	O
+social	O
+rented	O
+accommodation	O
+or	O
+who	O
+did	O
+not	O
+have	O
+access	O
+to	O
+a	O
+car	O
+were	O
+less	O
+likely	O
+to	O
+have	O
+returned	O
+usable	O
+data	O
+.	O
+
+Respondents	O
+reported	O
+a	O
+mean	O
+of	O
+318	O
+minutes	O
+'	O
+walking	O
+per	O
+week	O
+and	O
+a	O
+mean	O
+estimated	O
+total	O
+physical	O
+activity	O
+energy	O
+expenditure	O
+of	O
+3000	O
+MET	O
+-	O
+minutes	O
+per	O
+week	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+Only	O
+316	O
+respondents	O
+(	O
+38	O
+%	O
+)	O
+were	O
+categorised	O
+as	O
+having	O
+achieved	O
+a	O
+'	O
+high	O
+'	O
+(	O
+i	O
+.	O
+e	O
+.	O
+sufficient	O
+)	O
+level	O
+of	O
+physical	O
+activity	O
+.	O
+
+Correlates	O
+of	O
+active	O
+travel	O
+
+Active	O
+travel	O
+was	O
+significantly	O
+associated	O
+with	O
+being	O
+younger	O
+,	O
+living	O
+in	O
+owner	O
+-	O
+occupied	O
+accommodation	O
+,	O
+not	O
+having	O
+to	O
+travel	O
+more	O
+than	O
+four	O
+miles	O
+to	O
+work	O
+,	O
+having	O
+access	O
+to	O
+a	O
+bicycle	O
+,	O
+not	O
+having	O
+access	O
+to	O
+a	O
+car	O
+,	O
+and	O
+the	O
+absence	O
+of	O
+any	O
+difficulty	O
+walking	O
+.	O
+
+The	O
+final	O
+best	O
+model	O
+of	O
+the	O
+'	O
+personal	O
+'	O
+correlates	O
+of	O
+active	O
+travel	O
+provided	O
+satisfactory	O
+goodness	O
+-	O
+of	O
+-	O
+fit	O
+(	O
+Hosmer	O
+and	O
+Lemeshow	O
+test	O
+:	O
+chi	O
+2	O
+=	O
+13	O
+.	O
+04	O
+,	O
+df	O
+=	O
+8	O
+;	O
+P	O
+=	O
+0	O
+.	O
+11	O
+)	O
+and	O
+explained	O
+nearly	O
+one	O
+-	O
+fifth	O
+of	O
+the	O
+total	O
+variance	O
+in	O
+active	O
+travel	O
+(	O
+Nagelkerke	O
+'	O
+s	O
+R2	O
+=	O
+18	O
+.	O
+7	O
+%	O
+)	O
+(	O
+Table	O
+5	O
+)	O
+.	O
+
+Adding	O
+'	O
+environmental	O
+'	O
+variables	O
+to	O
+the	O
+model	O
+showed	O
+an	O
+additional	O
+significant	O
+positive	O
+association	O
+between	O
+active	O
+travel	O
+and	O
+perceived	O
+proximity	O
+to	O
+shops	O
+,	O
+and	O
+an	O
+additional	O
+significant	O
+negative	O
+association	O
+between	O
+active	O
+travel	O
+and	O
+perceived	O
+road	O
+safety	O
+for	O
+cyclists	O
+.	O
+
+The	O
+final	O
+best	O
+model	O
+of	O
+the	O
+personal	O
+and	O
+environmental	O
+correlates	O
+of	O
+active	O
+travel	O
+also	O
+provided	O
+satisfactory	O
+goodness	O
+-	O
+of	O
+-	O
+fit	O
+(	O
+Hosmer	O
+and	O
+Lemeshow	O
+test	O
+:	O
+chi	O
+2	O
+=	O
+10	O
+.	O
+61	O
+,	O
+df	O
+=	O
+8	O
+;	O
+P	O
+=	O
+0	O
+.	O
+23	O
+)	O
+and	O
+explained	O
+slightly	O
+more	O
+of	O
+the	O
+total	O
+variance	O
+in	O
+active	O
+travel	O
+than	O
+did	O
+the	O
+personal	O
+model	O
+alone	O
+(	O
+Nagelkerke	O
+'	O
+s	O
+R2	O
+=	O
+20	O
+.	O
+1	O
+%	O
+)	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+In	O
+order	O
+to	O
+aid	O
+interpretation	O
+,	O
+we	O
+also	O
+partitioned	O
+the	O
+dataset	O
+into	O
+two	O
+strata	O
+(	O
+'	O
+No	O
+car	O
+available	O
+'	O
+and	O
+'	O
+Car	O
+available	O
+'	O
+)	O
+and	O
+refitted	O
+the	O
+final	O
+model	O
+separately	O
+to	O
+each	O
+stratum	O
+of	O
+the	O
+dataset	O
+(	O
+Table	O
+6	O
+)	O
+.	O
+
+This	O
+showed	O
+that	O
+the	O
+subset	O
+of	O
+respondents	O
+with	O
+no	O
+access	O
+to	O
+a	O
+car	O
+accounted	O
+for	O
+the	O
+significant	O
+overall	O
+relationship	O
+between	O
+active	O
+travel	O
+and	O
+access	O
+to	O
+a	O
+bicycle	O
+,	O
+whereas	O
+those	O
+with	O
+access	O
+to	O
+a	O
+car	O
+accounted	O
+for	O
+the	O
+significant	O
+overall	O
+relationships	O
+with	O
+distance	O
+to	O
+place	O
+of	O
+work	O
+or	O
+study	O
+and	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+.	O
+
+The	O
+relationship	O
+with	O
+difficulty	O
+walking	O
+was	O
+also	O
+stronger	O
+in	O
+this	O
+group	O
+than	O
+in	O
+those	O
+without	O
+access	O
+to	O
+a	O
+car	O
+.	O
+
+Correlates	O
+of	O
+physical	O
+activity	O
+
+Physical	O
+activity	O
+was	O
+significantly	O
+associated	O
+with	O
+living	O
+in	O
+social	O
+-	O
+rented	O
+accommodation	O
+,	O
+not	O
+being	O
+overweight	O
+,	O
+and	O
+the	O
+absence	O
+of	O
+any	O
+difficulty	O
+walking	O
+.	O
+
+The	O
+final	O
+best	O
+model	O
+of	O
+the	O
+'	O
+personal	O
+'	O
+correlates	O
+of	O
+physical	O
+activity	O
+provided	O
+satisfactory	O
+goodness	O
+-	O
+of	O
+-	O
+fit	O
+(	O
+Hosmer	O
+and	O
+Lemeshow	O
+test	O
+:	O
+chi	O
+2	O
+=	O
+3	O
+.	O
+89	O
+,	O
+df	O
+=	O
+7	O
+;	O
+P	O
+=	O
+0	O
+.	O
+89	O
+)	O
+and	O
+explained	O
+about	O
+one	O
+-	O
+sixth	O
+of	O
+the	O
+total	O
+variance	O
+in	O
+physical	O
+activity	O
+(	O
+Nagelkerke	O
+'	O
+s	O
+R2	O
+=	O
+15	O
+.	O
+9	O
+%	O
+)	O
+(	O
+Table	O
+7	O
+)	O
+.	O
+
+Adding	O
+'	O
+environmental	O
+'	O
+variables	O
+to	O
+the	O
+model	O
+showed	O
+an	O
+additional	O
+significant	O
+negative	O
+association	O
+between	O
+physical	O
+activity	O
+and	O
+perception	O
+of	O
+traffic	O
+volume	O
+(	O
+i	O
+.	O
+e	O
+.	O
+respondents	O
+who	O
+perceived	O
+there	O
+to	O
+be	O
+a	O
+higher	O
+volume	O
+of	O
+traffic	O
+were	O
+more	O
+likely	O
+to	O
+report	O
+physical	O
+activity	O
+)	O
+.	O
+
+The	O
+final	O
+best	O
+model	O
+of	O
+the	O
+personal	O
+and	O
+environmental	O
+correlates	O
+of	O
+physical	O
+activity	O
+also	O
+provided	O
+satisfactory	O
+goodness	O
+-	O
+of	O
+-	O
+fit	O
+(	O
+Hosmer	O
+and	O
+Lemeshow	O
+test	O
+:	O
+chi	O
+2	O
+=	O
+3	O
+.	O
+86	O
+,	O
+df	O
+=	O
+8	O
+;	O
+P	O
+=	O
+0	O
+.	O
+87	O
+)	O
+and	O
+explained	O
+slightly	O
+more	O
+of	O
+the	O
+total	O
+variance	O
+in	O
+physical	O
+activity	O
+than	O
+did	O
+the	O
+personal	O
+model	O
+alone	O
+(	O
+Nagelkerke	O
+'	O
+s	O
+16	O
+.	O
+6	O
+%	O
+)	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+Discussion	O
+
+Principal	O
+findings	O
+
+In	O
+this	O
+deprived	O
+urban	O
+population	O
+,	O
+the	O
+likelihood	O
+of	O
+reporting	O
+active	O
+travel	O
+was	O
+associated	O
+with	O
+being	O
+younger	O
+,	O
+living	O
+in	O
+owner	O
+-	O
+occupied	O
+accommodation	O
+,	O
+not	O
+having	O
+to	O
+travel	O
+a	O
+long	O
+distance	O
+to	O
+work	O
+and	O
+not	O
+having	O
+access	O
+to	O
+a	O
+car	O
+,	O
+whereas	O
+overall	O
+physical	O
+activity	O
+was	O
+associated	O
+with	O
+living	O
+in	O
+social	O
+-	O
+rented	O
+accommodation	O
+and	O
+not	O
+being	O
+overweight	O
+.	O
+
+After	O
+adjusting	O
+for	O
+individual	O
+and	O
+household	O
+characteristics	O
+,	O
+neither	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+nor	O
+the	O
+objective	O
+proximity	O
+of	O
+respondents	O
+'	O
+homes	O
+to	O
+motorway	O
+or	O
+major	O
+road	O
+infrastructure	O
+appeared	O
+to	O
+explain	O
+much	O
+of	O
+the	O
+variance	O
+in	O
+active	O
+travel	O
+or	O
+overall	O
+physical	O
+activity	O
+,	O
+although	O
+we	O
+did	O
+find	O
+a	O
+significant	O
+positive	O
+association	O
+between	O
+active	O
+travel	O
+and	O
+perceived	O
+proximity	O
+to	O
+shops	O
+.	O
+
+Representativeness	O
+and	O
+completeness	O
+of	O
+survey	O
+data	O
+
+Our	O
+difficulty	O
+in	O
+obtaining	O
+a	O
+representative	O
+sample	O
+of	O
+the	O
+resident	O
+population	O
+is	O
+not	O
+unique	O
+to	O
+our	O
+study	O
+.	O
+
+Although	O
+our	O
+final	O
+response	O
+rate	O
+was	O
+low	O
+,	O
+it	O
+was	O
+almost	O
+identical	O
+to	O
+that	O
+achieved	O
+in	O
+a	O
+recent	O
+population	O
+-	O
+based	O
+intervention	O
+study	O
+elsewhere	O
+in	O
+Glasgow	O
+[	O
+22	O
+]	O
+.	O
+
+Some	O
+of	O
+the	O
+challenges	O
+of	O
+recruiting	O
+research	O
+participants	B
+in	O
+areas	O
+of	O
+deprivation	O
+have	O
+been	O
+described	O
+elsewhere	O
+[	O
+23	O
+]	O
+;	O
+these	O
+are	O
+superimposed	O
+on	O
+a	O
+downward	O
+trend	O
+in	O
+participation	O
+in	O
+even	O
+the	O
+best	O
+-	O
+resourced	O
+national	O
+population	O
+surveys	O
+[	O
+24	O
+]	O
+and	O
+an	O
+upward	O
+(	O
+and	O
+socially	O
+biased	O
+)	O
+trend	O
+in	O
+opt	O
+-	O
+outs	O
+from	O
+the	O
+main	O
+alternative	O
+sampling	O
+frame	O
+,	O
+the	O
+edited	O
+electoral	O
+register	O
+[	O
+25	O
+]	O
+.	O
+
+Although	O
+our	O
+achieved	O
+sample	O
+contained	O
+a	O
+higher	O
+proportion	O
+of	O
+respondents	O
+from	O
+owner	O
+-	O
+occupied	O
+and	O
+car	O
+-	O
+owning	O
+households	O
+than	O
+predicted	O
+from	O
+2001	O
+census	O
+data	O
+for	O
+the	O
+same	O
+census	O
+output	O
+areas	O
+,	O
+these	O
+differences	O
+may	O
+be	O
+partly	O
+accounted	O
+for	O
+by	O
+an	O
+upward	O
+background	O
+trend	O
+in	O
+owner	O
+occupation	O
+and	O
+car	O
+access	O
+between	O
+2001	O
+and	O
+2005	O
+.	O
+
+Our	O
+achieved	O
+sample	O
+is	O
+still	O
+clearly	O
+disadvantaged	O
+overall	O
+,	O
+in	O
+terms	O
+of	O
+socioeconomic	O
+and	O
+health	O
+status	O
+,	O
+compared	O
+with	O
+the	O
+country	O
+as	O
+a	O
+whole	O
+.	O
+
+It	O
+also	O
+contains	O
+sufficient	O
+heterogeneity	O
+to	O
+enable	O
+us	O
+to	O
+examine	O
+,	O
+in	O
+time	O
+,	O
+how	O
+the	O
+effects	O
+of	O
+the	O
+intervention	O
+are	O
+distributed	O
+between	O
+socioeconomic	O
+groups	O
+.	O
+
+We	O
+therefore	O
+consider	O
+our	O
+achieved	O
+sample	O
+fit	O
+for	O
+purpose	O
+.	O
+
+We	O
+had	O
+to	O
+disregard	O
+a	O
+substantial	O
+proportion	O
+of	O
+cases	O
+in	O
+analysis	O
+because	O
+respondents	O
+had	O
+returned	O
+unusable	O
+travel	O
+time	O
+data	O
+or	O
+had	O
+returned	O
+physical	O
+activity	O
+data	O
+that	O
+were	O
+incomplete	O
+,	O
+internally	O
+inconsistent	O
+or	O
+included	O
+a	O
+'	O
+Don	O
+'	O
+t	O
+know	O
+'	O
+response	O
+and	O
+were	O
+therefore	O
+unacceptable	O
+according	O
+to	O
+the	O
+IPAQ	O
+scoring	O
+protocol	O
+.	O
+
+Most	O
+published	O
+studies	O
+using	O
+the	O
+same	O
+,	O
+short	O
+form	O
+of	O
+IPAQ	O
+have	O
+either	O
+not	O
+reported	O
+the	O
+distribution	O
+of	O
+the	O
+continuous	O
+summary	O
+measures	O
+or	O
+have	O
+not	O
+reported	O
+data	O
+for	O
+the	O
+UK	O
+separately	O
+from	O
+those	O
+for	O
+other	O
+countries	O
+where	O
+higher	O
+levels	O
+of	O
+physical	O
+activity	O
+are	O
+reported	O
+.	O
+
+Despite	O
+the	O
+high	O
+proportion	O
+of	O
+missing	O
+physical	O
+activity	O
+data	O
+in	O
+our	O
+dataset	O
+,	O
+however	O
+,	O
+the	O
+aggregate	O
+continuous	O
+data	O
+we	O
+obtained	O
+were	O
+broadly	O
+comparable	O
+to	O
+those	O
+reported	O
+in	O
+R	O
+u	O
+tten	O
+and	O
+colleagues	O
+'	O
+study	O
+of	O
+a	O
+random	O
+sample	O
+of	O
+UK	O
+adults	O
+[	O
+26	O
+]	O
+.	O
+
+We	O
+could	O
+have	O
+included	O
+more	O
+cases	O
+in	O
+physical	O
+activity	O
+analysis	O
+by	O
+,	O
+for	O
+example	O
+,	O
+imputing	O
+missing	O
+values	O
+,	O
+but	O
+the	O
+results	O
+would	O
+not	O
+have	O
+been	O
+comparable	O
+with	O
+others	O
+'	O
+owing	O
+to	O
+the	O
+substantial	O
+deviations	O
+from	O
+the	O
+scoring	O
+protocol	O
+which	O
+would	O
+have	O
+been	O
+required	O
+.	O
+
+The	O
+frequency	O
+of	O
+unusable	O
+responses	O
+was	O
+not	O
+reported	O
+in	O
+the	O
+international	O
+multi	O
+-	O
+centre	O
+study	O
+which	O
+originally	O
+established	O
+the	O
+validity	O
+and	O
+reliability	O
+of	O
+IPAQ	O
+[	O
+27	O
+]	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+offering	O
+a	O
+'	O
+Don	O
+'	O
+t	O
+know	O
+'	O
+option	O
+in	O
+the	O
+self	O
+-	O
+completed	O
+IPAQ	O
+questionnaire	O
+encourages	O
+respondents	O
+to	O
+select	O
+this	O
+rather	O
+than	O
+to	O
+enter	O
+what	O
+may	O
+be	O
+a	O
+reasonably	O
+precise	O
+estimate	O
+of	O
+the	O
+actual	O
+time	O
+spent	O
+in	O
+physical	O
+activity	O
+;	O
+the	O
+respondent	O
+has	O
+no	O
+way	O
+of	O
+knowing	O
+that	O
+a	O
+single	O
+'	O
+Don	O
+'	O
+t	O
+know	O
+'	O
+response	O
+will	O
+result	O
+in	O
+all	O
+of	O
+their	O
+physical	O
+activity	O
+data	O
+being	O
+disregarded	O
+in	O
+analysis	O
+.	O
+
+This	O
+should	O
+be	O
+considered	O
+in	O
+any	O
+future	O
+revision	O
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+the	O
+IPAQ	O
+questionnaire	O
+and	O
+scoring	O
+protocol	O
+.	O
+
+Contribution	O
+of	O
+active	O
+travel	O
+to	O
+overall	O
+physical	O
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+
+The	O
+explanatory	O
+variables	O
+that	O
+were	O
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+associated	O
+with	O
+active	O
+travel	O
+but	O
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+(	O
+distance	O
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+place	O
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+work	O
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+study	O
+,	O
+access	O
+to	O
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+bicycle	O
+,	O
+access	O
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+,	O
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+to	O
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+,	O
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+perceived	O
+road	O
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+for	O
+cyclists	O
+)	O
+all	O
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+an	O
+obvious	O
+intuitive	O
+relationship	O
+with	O
+the	O
+use	O
+of	O
+walking	O
+or	O
+cycling	O
+as	O
+modes	O
+of	O
+transport	O
+.	O
+
+That	O
+they	O
+were	O
+not	O
+significantly	O
+associated	O
+with	O
+overall	O
+physical	O
+activity	O
+suggests	O
+either	O
+that	O
+active	O
+travel	O
+contributes	O
+only	O
+a	O
+minority	O
+of	O
+respondents	O
+'	O
+overall	O
+physical	O
+activity	O
+or	O
+that	O
+other	O
+factors	O
+not	O
+measured	O
+in	O
+this	O
+study	O
+are	O
+more	O
+important	O
+correlates	O
+of	O
+overall	O
+physical	O
+activity	O
+than	O
+those	O
+which	O
+determine	O
+active	O
+travel	O
+.	O
+
+A	O
+crude	O
+comparision	O
+of	O
+the	O
+quantity	O
+of	O
+active	O
+travel	O
+reported	O
+in	O
+the	O
+one	O
+-	O
+day	O
+travel	O
+diaries	O
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+the	O
+quantities	O
+of	O
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+using	O
+IPAQ	O
+suggests	O
+that	O
+on	O
+average	O
+,	O
+active	O
+travel	O
+may	O
+indeed	O
+make	O
+only	O
+a	O
+small	O
+(	O
+~	O
+15	O
+%	O
+)	O
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+to	O
+overall	O
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+activity	O
+in	O
+this	O
+study	O
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+.	O
+
+However	O
+,	O
+the	O
+real	O
+contribution	O
+may	O
+be	O
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+greater	O
+than	O
+this	O
+if	O
+,	O
+as	O
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+,	O
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+to	O
+over	O
+-	O
+report	O
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+IPAQ	O
+[	O
+28	O
+]	O
+.	O
+
+There	O
+can	O
+be	O
+little	O
+doubt	O
+that	O
+active	O
+travel	O
+makes	O
+a	O
+substantial	O
+contribution	O
+to	O
+the	O
+total	O
+quantity	O
+of	O
+walking	O
+reported	O
+in	O
+this	O
+study	O
+population	O
+.	O
+
+Irrespective	O
+of	O
+the	O
+true	O
+contribution	O
+of	O
+active	O
+travel	O
+to	O
+overall	O
+physical	O
+activity	O
+,	O
+however	O
+,	O
+it	O
+remains	O
+likely	O
+that	O
+other	O
+unmeasured	O
+personal	O
+and	O
+social	O
+factors	O
+beyond	O
+the	O
+scope	O
+of	O
+this	O
+study	O
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+more	O
+important	O
+correlates	O
+of	O
+overall	O
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+.	O
+
+Socio	O
+-	O
+spatial	O
+patterning	O
+of	O
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+
+Respondents	O
+living	O
+in	O
+owner	O
+-	O
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+report	O
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+travel	O
+than	O
+those	O
+living	O
+in	O
+social	O
+-	O
+rented	O
+accommodation	O
+,	O
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+less	O
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+report	O
+sufficient	O
+overall	O
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+activity	O
+.	O
+
+Since	O
+neither	O
+working	O
+situation	O
+nor	O
+perceived	O
+financial	O
+situation	O
+emerged	O
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+significantly	O
+associated	O
+with	O
+active	O
+travel	O
+or	O
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+,	O
+housing	O
+tenure	O
+and	O
+car	O
+access	O
+are	O
+the	O
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+explanatory	O
+variables	O
+in	O
+this	O
+dataset	O
+which	O
+can	O
+be	O
+interpreted	O
+as	O
+markers	O
+of	O
+socioeconomic	O
+status	O
+.	O
+
+Although	O
+having	O
+access	O
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+a	O
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+reflects	O
+the	O
+possession	O
+of	O
+a	O
+material	O
+asset	O
+,	O
+it	O
+has	O
+been	O
+argued	O
+that	O
+this	O
+is	O
+a	O
+less	O
+direct	O
+marker	O
+of	O
+socioeconomic	O
+status	O
+than	O
+some	O
+other	O
+markers	O
+because	O
+,	O
+in	O
+Scotland	O
+at	O
+least	O
+,	O
+access	O
+to	O
+a	O
+car	O
+is	O
+a	O
+more	O
+-	O
+or	O
+-	O
+less	O
+essential	O
+requirement	O
+for	O
+living	O
+in	O
+many	O
+rural	O
+areas	O
+,	O
+whereas	O
+it	O
+is	O
+possible	O
+to	O
+live	O
+in	O
+a	O
+dense	O
+urban	O
+settlement	O
+such	O
+as	O
+Glasgow	O
+without	O
+using	O
+a	O
+car	O
+.	O
+
+In	O
+the	O
+final	O
+models	O
+in	O
+this	O
+study	O
+,	O
+therefore	O
+,	O
+housing	O
+tenure	O
+may	O
+be	O
+regarded	O
+as	O
+the	O
+primary	O
+marker	O
+of	O
+socioeconomic	O
+status	O
+.	O
+
+The	O
+findings	O
+consequently	O
+suggest	O
+conflicting	O
+socioeconomic	O
+gradients	O
+in	O
+prevalence	O
+:	O
+more	O
+advantaged	O
+respondents	O
+were	O
+more	O
+likely	O
+to	O
+report	O
+active	O
+travel	O
+,	O
+but	O
+more	O
+disadvantaged	O
+respondents	O
+were	O
+more	O
+likely	O
+to	O
+report	O
+sufficient	O
+overall	O
+physical	O
+activity	O
+.	O
+
+The	O
+higher	O
+prevalence	O
+of	O
+sufficient	O
+overall	O
+physical	O
+activity	O
+among	O
+the	O
+more	O
+disadvantaged	O
+despite	O
+their	O
+lower	O
+propensity	O
+for	O
+active	O
+travel	O
+is	O
+likely	O
+to	O
+reflect	O
+higher	O
+quantities	O
+of	O
+physical	O
+activity	O
+in	O
+other	O
+domains	O
+,	O
+particularly	O
+occupational	O
+and	O
+domestic	O
+activities	O
+,	O
+since	O
+leisure	O
+-	O
+time	O
+physical	O
+activity	O
+tends	O
+to	O
+be	O
+higher	O
+among	O
+more	O
+advantaged	O
+groups	O
+[	O
+29	O
+]	O
+.	O
+
+Environmental	O
+characteristics	O
+:	O
+paradoxical	O
+,	O
+unmeasured	O
+,	O
+or	O
+irrelevant	O
+?	O
+
+The	O
+two	O
+environmental	O
+variables	O
+that	O
+emerged	O
+as	O
+significantly	O
+associated	O
+with	O
+active	O
+travel	O
+,	O
+particularly	O
+among	O
+those	O
+without	O
+access	O
+to	O
+a	O
+car	O
+,	O
+were	O
+perceived	O
+proximity	O
+to	O
+shops	O
+and	O
+perceived	O
+road	O
+safety	O
+for	O
+cyclists	O
+.	O
+
+The	O
+positive	O
+association	O
+with	O
+perceived	O
+proximity	O
+to	O
+shops	O
+suggests	O
+that	O
+for	O
+active	O
+travel	O
+to	O
+be	O
+undertaken	O
+in	O
+this	O
+population	O
+,	O
+it	O
+may	O
+be	O
+more	O
+important	O
+that	O
+people	B
+live	O
+close	O
+to	O
+the	O
+amenities	O
+they	O
+need	O
+than	O
+that	O
+they	O
+live	O
+in	O
+an	O
+environment	O
+with	O
+more	O
+favourable	O
+subjective	O
+or	O
+discretionary	O
+considerations	O
+such	O
+as	O
+attractiveness	O
+or	O
+noise	O
+.	O
+
+This	O
+would	O
+be	O
+consistent	O
+with	O
+an	O
+understanding	O
+that	O
+walking	O
+as	O
+a	O
+mode	O
+of	O
+transport	O
+is	O
+primarily	O
+a	O
+way	O
+of	O
+undertaking	O
+journeys	O
+which	O
+have	O
+to	O
+be	O
+made	O
+anyway	O
+,	O
+as	O
+opposed	O
+to	O
+more	O
+discretionary	O
+(	O
+recreational	O
+)	O
+forms	O
+of	O
+walking	O
+which	O
+may	O
+be	O
+more	O
+susceptible	O
+to	O
+the	O
+influence	O
+of	O
+less	O
+-	O
+structural	O
+characteristics	O
+.	O
+
+Although	O
+the	O
+negative	O
+association	O
+with	O
+perceived	O
+road	O
+safety	O
+for	O
+cyclists	O
+appears	O
+counter	O
+-	O
+intuitive	O
+,	O
+similar	O
+'	O
+paradoxical	O
+inverse	O
+relationships	O
+'	O
+have	O
+been	O
+reported	O
+elsewhere	O
+,	O
+for	O
+example	O
+by	O
+Titze	O
+and	O
+colleagues	O
+in	O
+a	O
+study	O
+of	O
+the	O
+correlates	O
+of	O
+cycling	O
+among	O
+students	O
+[	O
+30	O
+]	O
+and	O
+by	O
+Humpel	O
+and	O
+colleagues	O
+in	O
+a	O
+study	O
+of	O
+correlates	O
+of	O
+walking	O
+for	O
+pleasure	O
+[	O
+31	O
+]	O
+.	O
+
+Titze	O
+and	O
+colleagues	O
+suggest	O
+that	O
+respondents	O
+who	O
+cycle	O
+regularly	O
+are	O
+more	O
+likely	O
+to	O
+be	O
+aware	O
+of	O
+,	O
+and	O
+report	O
+,	O
+the	O
+danger	O
+posed	O
+by	O
+traffic	O
+than	O
+non	O
+-	O
+cyclists	O
+or	O
+infrequent	O
+cyclists	O
+.	O
+
+A	O
+similar	O
+phenomenon	O
+could	O
+explain	O
+the	O
+negative	O
+association	O
+between	O
+physical	O
+activity	O
+and	O
+perception	O
+of	O
+traffic	O
+volume	O
+.	O
+
+Overall	O
+,	O
+the	O
+influence	O
+of	O
+the	O
+putative	O
+environmental	O
+characteristics	O
+examined	O
+in	O
+this	O
+study	O
+on	O
+active	O
+travel	O
+and	O
+physical	O
+activity	O
+appeared	O
+small	O
+compared	O
+with	O
+that	O
+of	O
+the	O
+personal	O
+characteristics	O
+found	O
+to	O
+be	O
+significant	O
+,	O
+and	O
+including	O
+environmental	O
+characteristics	O
+in	O
+the	O
+models	O
+did	O
+not	O
+substantially	O
+modify	O
+the	O
+influence	O
+of	O
+personal	O
+characteristics	O
+.	O
+
+On	O
+the	O
+one	O
+hand	O
+,	O
+this	O
+could	O
+reflect	O
+an	O
+artefact	O
+of	O
+the	O
+research	O
+methods	O
+(	O
+a	O
+false	O
+negative	O
+error	O
+)	O
+,	O
+which	O
+could	O
+have	O
+arisen	O
+in	O
+various	O
+ways	O
+.	O
+
+In	O
+particular	O
+,	O
+the	O
+'	O
+wrong	O
+'	O
+environmental	O
+exposure	O
+may	O
+have	O
+been	O
+measured	O
+,	O
+in	O
+that	O
+the	O
+environmental	O
+characteristics	O
+examined	O
+were	O
+those	O
+of	O
+the	O
+immediate	O
+surroundings	O
+of	O
+respondents	O
+'	O
+homes	O
+,	O
+whereas	O
+the	O
+propensity	O
+to	O
+choose	O
+active	O
+modes	O
+of	O
+transport	O
+may	O
+be	O
+more	O
+strongly	O
+influenced	O
+by	O
+the	O
+characteristics	O
+of	O
+the	O
+environment	O
+elsewhere	O
+on	O
+their	O
+routes	O
+[	O
+30	O
+]	O
+,	O
+for	O
+example	O
+the	O
+perceived	O
+danger	O
+of	O
+cycling	O
+in	O
+the	O
+city	O
+centre	O
+-	O
+an	O
+association	O
+which	O
+may	O
+be	O
+absent	O
+,	O
+or	O
+at	O
+least	O
+diluted	O
+,	O
+when	O
+the	O
+'	O
+exposure	O
+'	O
+examined	O
+is	O
+limited	O
+to	O
+the	O
+residential	O
+environment	O
+.	O
+
+It	O
+could	O
+also	O
+be	O
+argued	O
+that	O
+the	O
+apparently	O
+weak	O
+influence	O
+of	O
+environmental	O
+characteristics	O
+in	O
+this	O
+study	O
+reflects	O
+a	O
+reliance	O
+on	O
+respondents	O
+'	O
+perceptions	O
+which	O
+have	O
+not	O
+been	O
+objectively	O
+verified	O
+and	O
+may	O
+therefore	O
+be	O
+a	O
+weak	O
+proxy	O
+for	O
+the	O
+'	O
+true	O
+'	O
+objectively	O
+-	O
+measured	O
+characteristics	O
+of	O
+their	O
+surroundings	O
+.	O
+
+However	O
+,	O
+as	O
+recent	O
+reviews	O
+have	O
+pointed	O
+out	O
+,	O
+the	O
+current	O
+weight	O
+of	O
+evidence	O
+for	O
+objective	O
+environmental	O
+correlates	O
+of	O
+walking	O
+is	O
+no	O
+greater	O
+than	O
+that	O
+for	O
+subjective	O
+environmental	O
+correlates	O
+[	O
+5	O
+]	O
+and	O
+it	O
+is	O
+entirely	O
+plausible	O
+that	O
+people	B
+'	O
+s	O
+perceptions	O
+of	O
+their	O
+environment	O
+may	O
+be	O
+at	O
+least	O
+as	O
+important	O
+as	O
+their	O
+objective	O
+conditions	O
+in	O
+influencing	O
+their	O
+behaviour	O
+[	O
+6	O
+]	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+we	O
+may	O
+have	O
+demonstrated	O
+a	O
+real	O
+absence	O
+of	O
+any	O
+major	O
+association	O
+.	O
+
+Although	O
+at	O
+first	O
+sight	O
+this	O
+appears	O
+at	O
+odds	O
+with	O
+the	O
+growing	O
+body	O
+of	O
+review	O
+-	O
+level	O
+evidence	O
+for	O
+environmental	O
+correlates	O
+of	O
+physical	O
+activity	O
+,	O
+Wendel	O
+-	O
+Vos	O
+and	O
+colleagues	O
+noted	O
+that	O
+of	O
+all	O
+the	O
+environmental	O
+factors	O
+examined	O
+in	O
+all	O
+the	O
+studies	O
+included	O
+in	O
+their	O
+review	O
+,	O
+analysis	O
+showed	O
+a	O
+'	O
+null	O
+association	O
+'	O
+in	O
+76	O
+%	O
+of	O
+cases	O
+[	O
+9	O
+]	O
+,	O
+and	O
+our	O
+finding	O
+that	O
+personal	O
+factors	O
+account	O
+for	O
+a	O
+much	O
+larger	O
+proportion	O
+of	O
+the	O
+variance	O
+in	O
+active	O
+travel	O
+or	O
+physical	O
+activity	O
+than	O
+is	O
+accounted	O
+for	O
+by	O
+environmental	O
+factors	O
+is	O
+consistent	O
+with	O
+those	O
+of	O
+some	O
+other	O
+European	O
+studies	O
+[	O
+32	O
+,	O
+33	O
+]	O
+.	O
+
+In	O
+the	O
+particular	O
+context	O
+of	O
+this	O
+study	O
+,	O
+residents	O
+may	O
+simply	O
+have	O
+adapted	O
+to	O
+adverse	O
+conditions	O
+in	O
+their	O
+local	O
+environment	O
+in	O
+the	O
+ways	O
+identified	O
+by	O
+Hedges	O
+in	O
+a	O
+qualitative	O
+study	O
+of	O
+people	B
+living	O
+close	O
+to	O
+new	O
+roads	O
+built	O
+in	O
+the	O
+UK	O
+in	O
+the	O
+1970s	O
+[	O
+34	O
+]	O
+-	O
+particularly	O
+by	O
+attitudinal	O
+adaptation	O
+,	O
+which	O
+Hedges	O
+characterises	O
+as	O
+developing	O
+an	O
+attitude	O
+that	O
+it	O
+is	O
+futile	O
+to	O
+resist	O
+.	O
+
+One	O
+can	O
+imagine	O
+that	O
+in	O
+the	O
+most	O
+deprived	O
+areas	O
+of	O
+Glasgow	O
+,	O
+people	B
+may	O
+have	O
+become	O
+resigned	O
+to	O
+the	O
+nature	O
+of	O
+their	O
+surroundings	O
+,	O
+seeing	O
+them	O
+as	O
+inevitable	O
+and	O
+not	O
+amenable	O
+to	O
+change	O
+either	O
+through	O
+environmental	O
+improvement	O
+or	O
+through	O
+their	O
+moving	O
+to	O
+another	O
+area	O
+.	O
+
+Conclusion	O
+
+After	O
+demographic	O
+and	O
+socioeconomic	O
+characteristics	O
+were	O
+taken	O
+into	O
+account	O
+,	O
+neither	O
+perceptions	O
+of	O
+the	O
+local	O
+environment	O
+nor	O
+objective	O
+proximity	O
+to	O
+major	O
+road	O
+infrastructure	O
+appeared	O
+to	O
+explain	O
+much	O
+of	O
+the	O
+variance	O
+in	O
+active	O
+travel	O
+or	O
+overall	O
+physical	O
+activity	O
+in	O
+this	O
+study	O
+.	O
+
+Our	O
+study	O
+population	O
+may	O
+be	O
+both	O
+objectively	O
+constrained	O
+by	O
+their	O
+socioeconomic	O
+circumstances	O
+(	O
+including	O
+comparatively	O
+limited	O
+access	O
+to	O
+private	O
+cars	O
+)	O
+and	O
+adapted	O
+to	O
+living	O
+in	O
+conditions	O
+which	O
+others	O
+would	O
+consider	O
+to	O
+pose	O
+a	O
+barrier	O
+to	O
+active	O
+travel	O
+.	O
+
+Under	O
+these	O
+circumstances	O
+,	O
+environmental	O
+characteristics	O
+which	O
+have	O
+been	O
+found	O
+to	O
+influence	O
+discretionary	O
+active	O
+travel	O
+in	O
+studies	O
+in	O
+other	O
+,	O
+more	O
+affluent	O
+populations	O
+may	O
+simply	O
+be	O
+irrelevant	O
+in	O
+a	O
+population	O
+which	O
+is	O
+more	O
+captive	O
+in	O
+its	O
+travel	O
+choices	O
+.	O
+
+Environmental	O
+correlates	O
+of	O
+active	O
+travel	O
+should	O
+not	O
+be	O
+assumed	O
+to	O
+be	O
+generalisable	O
+between	O
+populations	O
+;	O
+researchers	O
+should	O
+continue	O
+to	O
+test	O
+hypotheses	O
+about	O
+putative	O
+environmental	O
+correlates	O
+in	O
+different	O
+settings	O
+,	O
+and	O
+policymakers	O
+should	O
+recognise	O
+that	O
+the	O
+effects	O
+of	O
+interventions	O
+to	O
+change	O
+the	O
+environment	O
+are	O
+likely	O
+to	O
+vary	O
+between	O
+populations	O
+and	O
+between	O
+socioeconomic	O
+groups	O
+within	O
+populations	O
+.	O
+
+Competing	O
+interests	O
+
+This	O
+paper	O
+is	O
+based	O
+on	O
+material	O
+contained	O
+in	O
+the	O
+first	O
+author	O
+'	O
+s	O
+PhD	O
+thesis	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+DO	O
+had	O
+the	O
+original	O
+idea	O
+for	O
+the	O
+study	O
+,	O
+designed	O
+the	O
+study	O
+and	O
+the	O
+survey	O
+materials	O
+,	O
+applied	O
+for	O
+ethical	O
+approval	O
+,	O
+cleaned	O
+and	O
+coded	O
+the	O
+survey	O
+data	O
+,	O
+carried	O
+out	O
+all	O
+the	O
+geographical	O
+and	O
+statistical	O
+analyses	O
+and	O
+wrote	O
+the	O
+paper	O
+.	O
+
+MP	O
+was	O
+DO	O
+'	O
+s	O
+PhD	O
+supervisor	O
+.	O
+
+RM	O
+,	O
+NM	O
+,	O
+MP	O
+and	O
+SP	O
+constituted	O
+the	O
+steering	O
+group	O
+for	O
+the	O
+study	O
+,	O
+contributed	O
+to	O
+and	O
+advised	O
+on	O
+the	O
+design	O
+of	O
+the	O
+study	O
+and	O
+the	O
+interpretation	O
+of	O
+the	O
+emerging	O
+findings	O
+,	O
+and	O
+contributed	O
+to	O
+the	O
+critical	O
+revision	O
+of	O
+the	O
+paper	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Supplementary	O
+Material	O
+
+Foamy	O
+Macrophages	O
+from	O
+Tuberculous	O
+Patients	B
+'	O
+Granulomas	O
+Constitute	O
+a	O
+Nutrient	O
+-	O
+Rich	O
+Reservoir	O
+for	O
+M	B
+.	I
+tuberculosis	I
+Persistence	O
+
+Abstract	O
+
+Tuberculosis	O
+(	O
+TB	O
+)	O
+is	O
+characterized	O
+by	O
+a	O
+tight	O
+interplay	O
+between	O
+Mycobacterium	B
+tuberculosis	I
+and	O
+host	O
+cells	O
+within	O
+granulomas	O
+.	O
+
+These	O
+cellular	O
+aggregates	O
+restrict	O
+bacterial	O
+spreading	O
+,	O
+but	O
+do	O
+not	O
+kill	O
+all	O
+the	O
+bacilli	O
+,	O
+which	O
+can	O
+persist	O
+for	O
+years	O
+.	O
+
+In	O
+-	O
+depth	O
+investigation	O
+of	O
+M	B
+.	I
+tuberculosis	I
+interactions	O
+with	O
+granuloma	O
+-	O
+specific	O
+cell	O
+populations	O
+are	O
+needed	O
+to	O
+gain	O
+insight	O
+into	O
+mycobacterial	O
+persistence	O
+,	O
+and	O
+to	O
+better	O
+understand	O
+the	O
+physiopathology	O
+of	O
+the	O
+disease	O
+.	O
+
+We	O
+have	O
+analyzed	O
+the	O
+formation	O
+of	O
+foamy	O
+macrophages	O
+(	O
+FMs	O
+)	O
+,	O
+a	O
+granuloma	O
+-	O
+specific	O
+cell	O
+population	O
+characterized	O
+by	O
+its	O
+high	O
+lipid	O
+content	O
+,	O
+and	O
+studied	O
+their	O
+interaction	O
+with	O
+the	O
+tubercle	O
+bacillus	O
+.	O
+
+Within	O
+our	O
+in	O
+vitro	O
+human	B
+granuloma	O
+model	O
+,	O
+M	B
+.	I
+tuberculosis	I
+long	O
+chain	O
+fatty	O
+acids	O
+,	O
+namely	O
+oxygenated	O
+mycolic	O
+acids	O
+(	O
+MA	O
+)	O
+,	O
+triggered	O
+the	O
+differentiation	O
+of	O
+human	B
+monocyte	O
+-	O
+derived	O
+macrophages	O
+into	O
+FMs	O
+.	O
+
+In	O
+these	O
+cells	O
+,	O
+mycobacteria	O
+no	O
+longer	O
+replicated	O
+and	O
+switched	O
+to	O
+a	O
+dormant	O
+non	O
+-	O
+replicative	O
+state	O
+.	O
+
+Electron	O
+microscopy	O
+observation	O
+of	O
+M	B
+.	I
+tuberculosis	I
+-	O
+infected	O
+FMs	O
+showed	O
+that	O
+the	O
+mycobacteria	O
+-	O
+containing	O
+phagosomes	O
+migrate	O
+towards	O
+host	O
+cell	O
+lipid	O
+bodies	O
+(	O
+LB	O
+)	O
+,	O
+a	O
+process	O
+which	O
+culminates	O
+with	O
+the	O
+engulfment	O
+of	O
+the	O
+bacillus	O
+into	O
+the	O
+lipid	O
+droplets	O
+and	O
+with	O
+the	O
+accumulation	O
+of	O
+lipids	O
+within	O
+the	O
+microbe	O
+.	O
+
+Altogether	O
+,	O
+our	O
+results	O
+suggest	O
+that	O
+oxygenated	O
+mycolic	O
+acids	O
+from	O
+M	B
+.	I
+tuberculosis	I
+play	O
+a	O
+crucial	O
+role	O
+in	O
+the	O
+differentiation	O
+of	O
+macrophages	O
+into	O
+FMs	O
+.	O
+
+These	O
+cells	O
+might	O
+constitute	O
+a	O
+reservoir	O
+used	O
+by	O
+the	O
+tubercle	O
+bacillus	O
+for	O
+long	O
+-	O
+term	O
+persistence	O
+within	O
+its	O
+human	B
+host	O
+,	O
+and	O
+could	O
+provide	O
+a	O
+relevant	O
+model	O
+for	O
+the	O
+screening	O
+of	O
+new	O
+antimicrobials	O
+against	O
+non	O
+-	O
+replicating	O
+persistent	O
+mycobacteria	O
+.	O
+
+Introduction	O
+
+Tuberculosis	O
+caused	O
+by	O
+Mycobacterium	B
+tuberculosis	I
+(	O
+M	B
+.	I
+tb	I
+)	O
+remains	O
+one	O
+of	O
+the	O
+leading	O
+causes	O
+of	O
+mortality	O
+in	O
+the	O
+world	O
+,	O
+with	O
+around	O
+2	O
+million	O
+deaths	O
+each	O
+year	O
+[	O
+1	O
+]	O
+.	O
+
+Most	O
+individuals	O
+remain	O
+asymptomatic	O
+after	O
+the	O
+primary	O
+infection	O
+with	O
+only	O
+10	O
+%	O
+at	O
+risk	O
+of	O
+developing	O
+an	O
+active	O
+disease	O
+during	O
+their	O
+life	O
+[	O
+2	O
+]	O
+.	O
+
+In	O
+asymptomatic	O
+individuals	O
+,	O
+the	O
+bacilli	O
+are	O
+not	O
+cleared	O
+but	O
+rather	O
+persist	O
+in	O
+a	O
+dormant	O
+state	O
+,	O
+from	O
+which	O
+they	O
+may	O
+reactivate	O
+and	O
+induce	O
+clinical	O
+disease	O
+at	O
+later	O
+stages	O
+[	O
+3	O
+]	O
+.	O
+
+The	O
+prognosis	O
+of	O
+the	O
+disease	O
+depends	O
+on	O
+the	O
+host	O
+'	O
+s	O
+efficiency	O
+to	O
+constrain	O
+the	O
+bacilli	O
+at	O
+the	O
+site	O
+of	O
+infection	O
+.	O
+
+When	O
+inhaled	O
+M	B
+.	I
+tb	I
+reach	O
+the	O
+lungs	O
+,	O
+they	O
+are	O
+internalized	O
+by	O
+lung	O
+macrophages	O
+.	O
+
+The	O
+latter	O
+trigger	O
+the	O
+accumulation	O
+at	O
+the	O
+infectious	O
+site	O
+of	O
+macrophages	O
+,	O
+lymphocytes	O
+and	O
+dendritic	O
+cells	O
+,	O
+to	O
+form	O
+a	O
+granuloma	O
+,	O
+which	O
+is	O
+a	O
+major	O
+histo	O
+-	O
+pathological	O
+feature	O
+of	O
+TB	O
+.	O
+
+Within	O
+granulomas	O
+,	O
+macrophages	O
+differentiate	O
+into	O
+epithelio	O
+i	O
+d	O
+cells	O
+(	O
+differentiated	O
+macrophages	O
+)	O
+,	O
+and	O
+/	O
+or	O
+fuse	O
+to	O
+form	O
+multinucleated	O
+giant	O
+cells	O
+(	O
+MGC	O
+)	O
+.	O
+
+Macrophages	O
+with	O
+large	O
+numbers	O
+of	O
+lipid	O
+-	O
+free	O
+vacuoles	O
+,	O
+as	O
+well	O
+as	O
+macrophages	O
+filled	O
+with	O
+lipid	O
+-	O
+containing	O
+bodies	O
+,	O
+also	O
+called	O
+foamy	O
+macrophages	O
+(	O
+FM	O
+)	O
+are	O
+also	O
+found	O
+within	O
+granulomatous	O
+structures	O
+in	O
+both	O
+experimental	O
+animal	O
+models	O
+and	O
+human	B
+disease	O
+[	O
+4	O
+]	O
+,	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+above	O
+cells	O
+are	O
+surrounded	O
+by	O
+a	O
+rim	O
+of	O
+lymphocytes	O
+,	O
+and	O
+at	O
+later	O
+stages	O
+,	O
+a	O
+tight	O
+coat	O
+of	O
+fibroblasts	O
+encloses	O
+the	O
+structure	O
+[	O
+6	O
+]	O
+.	O
+
+Although	O
+the	O
+structure	O
+and	O
+cell	O
+composition	O
+of	O
+granulomas	O
+are	O
+well	O
+known	O
+,	O
+the	O
+biology	O
+of	O
+these	O
+inflammatory	O
+structures	O
+and	O
+,	O
+more	O
+specifically	O
+,	O
+the	O
+role	O
+of	O
+granuloma	O
+-	O
+specific	O
+cell	O
+types	O
+,	O
+remain	O
+largely	O
+unknown	O
+.	O
+
+We	O
+have	O
+previously	O
+developed	O
+an	O
+in	O
+vitro	O
+model	O
+of	O
+human	B
+tuberculous	O
+granulomas	O
+to	O
+gain	O
+insight	O
+into	O
+the	O
+survival	O
+strategies	O
+of	O
+the	O
+tubercle	O
+bacillus	O
+within	O
+its	O
+human	B
+host	O
+.	O
+
+This	O
+model	O
+now	O
+enables	O
+the	O
+characterization	O
+of	O
+granuloma	O
+-	O
+specific	O
+cell	O
+types	O
+,	O
+and	O
+their	O
+modulation	O
+by	O
+M	B
+.	I
+tb	I
+[	O
+7	O
+]	O
+.	O
+
+The	O
+main	O
+advantage	O
+of	O
+this	O
+model	O
+over	O
+in	O
+vivo	O
+animal	O
+models	O
+or	O
+ex	O
+vivo	O
+human	B
+biopsy	O
+samples	O
+,	O
+is	O
+the	O
+availability	O
+of	O
+live	O
+granuloma	O
+cells	O
+which	O
+facilitates	O
+analysis	O
+of	O
+their	O
+cell	O
+biology	O
+.	O
+
+Using	O
+this	O
+model	O
+we	O
+have	O
+recently	O
+shown	O
+that	O
+,	O
+within	O
+granulomas	O
+,	O
+large	O
+multinucleated	O
+giant	O
+cells	O
+,	O
+also	O
+known	O
+as	O
+Langhans	O
+giant	O
+cells	O
+,	O
+result	O
+from	O
+the	O
+induction	O
+of	O
+granuloma	O
+macrophage	O
+fusion	O
+by	O
+M	B
+.	I
+tb	I
+glycolipids	O
+[	O
+8	O
+]	O
+.	O
+
+We	O
+have	O
+shown	O
+that	O
+these	O
+cells	O
+have	O
+lost	O
+the	O
+ability	O
+to	O
+mediate	O
+bacterial	O
+uptake	O
+upon	O
+maturation	O
+,	O
+but	O
+have	O
+conserved	O
+their	O
+ability	O
+to	O
+mediate	O
+antigen	O
+presentation	O
+[	O
+9	O
+]	O
+.	O
+
+The	O
+differentiation	O
+of	O
+macrophages	O
+into	O
+FMs	O
+has	O
+been	O
+particularly	O
+well	O
+described	O
+in	O
+individuals	O
+developing	O
+a	O
+postprimary	O
+,	O
+also	O
+known	O
+as	O
+secondary	O
+or	O
+adult	O
+,	O
+TB	O
+.	O
+
+These	O
+postprimary	O
+infections	O
+are	O
+considered	O
+to	O
+be	O
+the	O
+result	O
+of	O
+re	O
+-	O
+infection	O
+or	O
+reactivation	O
+of	O
+a	O
+primary	O
+TB	O
+[	O
+10	O
+]	O
+.	O
+
+FMs	O
+have	O
+been	O
+described	O
+in	O
+leprosy	O
+patients	B
+or	O
+M	B
+.	I
+avium	I
+-	O
+infected	O
+AIDS	O
+(	O
+Acquired	O
+ImmunoDeficiency	O
+Syndrome	O
+)	O
+patients	B
+,	O
+and	O
+in	O
+chronic	O
+stages	O
+of	O
+M	B
+.	I
+tb	I
+infection	O
+in	O
+mice	B
+[	O
+4	O
+]	O
+,	O
+[	O
+11	O
+]	O
+,	O
+[	O
+12	O
+]	O
+.	O
+
+The	O
+foamy	O
+aspect	O
+of	O
+these	O
+macrophages	O
+is	O
+the	O
+result	O
+of	O
+intracellular	O
+lipid	O
+accumulation	O
+within	O
+lipid	O
+bodies	O
+,	O
+also	O
+called	O
+lipid	O
+droplets	O
+or	O
+lipid	O
+vacuoles	O
+[	O
+13	O
+]	O
+,	O
+[	O
+14	O
+]	O
+,	O
+[	O
+15	O
+]	O
+.	O
+
+In	O
+an	O
+experimental	O
+model	O
+of	O
+leukocyte	O
+infection	O
+,	O
+it	O
+was	O
+recently	O
+suggested	O
+that	O
+BCG	O
+(	O
+Bacille	O
+Calmette	O
+Guerin	O
+)	O
+infection	O
+can	O
+induce	O
+,	O
+in	O
+a	O
+TLR2	O
+-	O
+dependent	O
+fashion	O
+,	O
+the	O
+rapid	O
+formation	O
+of	O
+lipid	O
+bodies	O
+carrying	O
+out	O
+part	O
+of	O
+the	O
+eicosano	O
+i	O
+d	O
+biosynthesis	O
+that	O
+usually	O
+accompanies	O
+the	O
+infection	O
+,	O
+thus	O
+pointing	O
+to	O
+an	O
+active	O
+role	O
+for	O
+lipid	O
+bodies	O
+during	O
+the	O
+course	O
+of	O
+infection	O
+[	O
+16	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+mechanisms	O
+regulating	O
+this	O
+lipid	O
+accumulation	O
+during	O
+mycobacterial	O
+infection	O
+and	O
+their	O
+significance	O
+in	O
+the	O
+physiopathology	O
+of	O
+tuberculosis	O
+are	O
+not	O
+understood	O
+.	O
+
+Most	O
+of	O
+the	O
+studies	O
+on	O
+TB	O
+granulomas	O
+have	O
+focused	O
+on	O
+the	O
+contribution	O
+of	O
+host	O
+components	O
+,	O
+but	O
+very	O
+little	O
+is	O
+known	O
+about	O
+the	O
+role	O
+played	O
+by	O
+bacterial	O
+constituents	O
+in	O
+terms	O
+of	O
+granuloma	O
+formation	O
+and	O
+progression	O
+.	O
+
+The	O
+present	O
+work	O
+was	O
+aimed	O
+at	O
+deciphering	O
+the	O
+role	O
+of	O
+FMs	O
+in	O
+M	B
+.	I
+tb	I
+survival	O
+within	O
+human	B
+granulomas	O
+.	O
+
+To	O
+test	O
+our	O
+working	O
+hypothesis	O
+according	O
+to	O
+which	O
+FMs	O
+constitute	O
+a	O
+nutrient	O
+-	O
+rich	O
+reservoir	O
+for	O
+M	B
+.	I
+tb	I
+persistence	O
+,	O
+we	O
+used	O
+our	O
+in	O
+vitro	O
+model	O
+of	O
+human	B
+granulomas	O
+to	O
+analyze	O
+the	O
+formation	O
+of	O
+FMs	O
+and	O
+their	O
+role	O
+during	O
+M	B
+.	I
+tb	I
+infection	O
+.	O
+
+We	O
+showed	O
+that	O
+only	O
+highly	O
+virulent	O
+mycobacteria	O
+(	O
+M	B
+.	I
+tb	I
+,	O
+M	B
+.	I
+avium	I
+)	O
+and	O
+not	O
+saprophytic	O
+ones	O
+(	O
+M	B
+.	I
+smegmatis	I
+)	O
+could	O
+induce	O
+the	O
+formation	O
+of	O
+FMs	O
+in	O
+mature	O
+granulomas	O
+.	O
+
+Moreover	O
+,	O
+we	O
+demonstrated	O
+that	O
+oxygenated	O
+mycolic	O
+acids	O
+specifically	O
+produced	O
+by	O
+the	O
+above	O
+pathogenic	O
+species	O
+were	O
+responsible	O
+for	O
+FMs	O
+formation	O
+.	O
+
+Once	O
+differentiated	O
+,	O
+FMs	O
+were	O
+unable	O
+to	O
+mediate	O
+phagocytosis	O
+of	O
+new	O
+bacilli	O
+and	O
+their	O
+microbicidal	O
+activity	O
+was	O
+reduced	O
+.	O
+
+M	B
+.	I
+tb	I
+was	O
+not	O
+killed	O
+in	O
+FMs	O
+but	O
+instead	O
+persisted	O
+in	O
+a	O
+non	O
+-	O
+replicating	O
+state	O
+,	O
+and	O
+over	O
+-	O
+expressed	O
+dormancy	O
+genes	O
+.	O
+
+Noteworthy	O
+,	O
+in	O
+foamy	O
+macrophages	O
+,	O
+M	B
+.	I
+tb	I
+-	O
+containing	O
+phagosomes	O
+were	O
+shown	O
+to	O
+migrate	O
+towards	O
+lipid	O
+bodies	O
+which	O
+they	O
+progressively	O
+surrounded	O
+and	O
+engulfed	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+bacteria	O
+were	O
+freed	O
+into	O
+lipid	O
+bodies	O
+,	O
+thus	O
+favoring	O
+the	O
+bacilli	O
+'	O
+s	O
+access	O
+to	O
+nutrients	O
+.	O
+
+From	O
+these	O
+data	O
+,	O
+we	O
+propose	O
+that	O
+FMs	O
+could	O
+form	O
+a	O
+secure	O
+reservoir	O
+for	O
+the	O
+tubercle	O
+bacilli	O
+.	O
+
+Methods	O
+
+Human	B
+samples	O
+
+Human	B
+blood	O
+samples	O
+,	O
+purchased	O
+from	O
+the	O
+French	O
+National	O
+Blood	O
+provider	O
+of	O
+Toulouse	O
+,	O
+were	O
+collected	O
+from	O
+fully	O
+anonymized	O
+non	O
+-	O
+tuberculous	O
+control	O
+donors	O
+,	O
+an	O
+ethical	O
+committee	O
+approval	O
+was	O
+,	O
+therefore	O
+,	O
+not	O
+necessary	O
+.	O
+
+This	O
+study	O
+was	O
+conducted	O
+according	O
+to	O
+the	O
+principles	O
+expressed	O
+in	O
+the	O
+Helsinki	O
+Declaration	O
+,	O
+with	O
+informed	O
+consent	O
+obtained	O
+from	O
+each	O
+donor	O
+.	O
+
+We	O
+chose	O
+to	O
+work	O
+on	O
+lymph	O
+node	O
+samples	O
+rather	O
+than	O
+lung	O
+biopsies	O
+,	O
+which	O
+are	O
+usually	O
+only	O
+paraffin	O
+-	O
+embedded	O
+,	O
+because	O
+staining	O
+for	O
+lipids	O
+can	O
+only	O
+be	O
+performed	O
+on	O
+frozen	O
+samples	O
+.	O
+
+Lymph	O
+node	O
+biopsies	O
+were	O
+taken	O
+for	O
+diagnosis	O
+purposes	O
+,	O
+in	O
+ten	O
+non	O
+-	O
+HIV	B
+patients	B
+.	O
+
+For	O
+each	O
+biopsy	O
+,	O
+a	O
+fragment	O
+was	O
+sent	O
+to	O
+the	O
+microbiology	O
+laboratory	O
+,	O
+another	O
+was	O
+frozen	O
+in	O
+liquid	O
+nitrogen	O
+and	O
+the	O
+main	O
+part	O
+was	O
+fixed	O
+in	O
+formalin	O
+and	O
+paraffin	O
+-	O
+embedded	O
+for	O
+histological	O
+examination	O
+.	O
+
+M	B
+.	I
+tb	I
+was	O
+identified	O
+in	O
+9	O
+lymph	O
+node	O
+biopsies	O
+and	O
+from	O
+the	O
+lung	O
+aspiration	O
+in	O
+the	O
+last	O
+patient	B
+.	O
+
+This	O
+latter	O
+case	O
+showed	O
+no	O
+signs	O
+of	O
+necrosis	O
+,	O
+and	O
+no	O
+FMs	O
+were	O
+found	O
+in	O
+the	O
+lymph	O
+node	O
+biopsy	O
+.	O
+
+This	O
+study	O
+complies	O
+with	O
+the	O
+guidelines	O
+of	O
+the	O
+declaration	O
+of	O
+Helsinki	O
+.	O
+
+Bacterial	O
+strains	O
+and	O
+culture	O
+conditions	O
+
+Wild	O
+-	O
+type	O
+M	B
+.	I
+smegmatis	I
+and	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+strains	O
+were	O
+previously	O
+described	O
+[	O
+17	O
+]	O
+,	O
+M	B
+.	I
+tuberculosis	I
+-	O
+GFP	O
+were	O
+a	O
+kind	O
+gift	O
+from	O
+Dr	O
+.	O
+C	O
+.	O
+
+Guilhot	O
+(	O
+CNRS	O
+-	O
+IPBS	O
+,	O
+Toulouse	O
+France	O
+)	O
+.	O
+
+Bacilli	O
+were	O
+grown	O
+in	O
+Middlebrook	O
+7H9	O
+medium	O
+(	O
+Difco	O
+)	O
+supplemented	O
+with	O
+10	O
+%	O
+albumin	O
+-	O
+dextrose	O
+-	O
+catalase	O
+(	O
+Difco	O
+)	O
+.	O
+
+Fluorescent	O
+M	B
+.	I
+smegmatis	I
+and	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+were	O
+obtained	O
+by	O
+FITC	O
+labelling	O
+as	O
+described	O
+in	O
+[	O
+18	O
+]	O
+.	O
+
+Isolation	O
+of	O
+RNA	O
+from	O
+intraphagosomal	O
+M	B
+.	I
+tb	I
+
+Six	O
+and	O
+12	O
+days	O
+post	O
+-	O
+infection	O
+(	O
+MOI	O
+10	O
+)	O
+,	O
+macrophages	O
+and	O
+FMs	O
+(	O
+5	O
+x	O
+106	O
+)	O
+were	O
+washed	O
+twice	O
+with	O
+PBS	O
+,	O
+scraped	O
+off	O
+the	O
+cell	O
+dishes	O
+and	O
+recovered	O
+by	O
+centrifugation	O
+.	O
+
+The	O
+cell	O
+pellets	O
+were	O
+lysed	O
+with	O
+lysis	O
+buffer	O
+(	O
+RNEasy	O
+mini	O
+kit	O
+,	O
+Quiagen	O
+)	O
+and	O
+transferred	O
+to	O
+2	O
+ml	O
+Eppendorf	O
+-	O
+tubes	O
+containing	O
+a	O
+0	O
+.	O
+5	O
+ml	O
+suspension	O
+of	O
+0	O
+.	O
+1	O
+mm	O
+-	O
+diameter	O
+glass	O
+beads	O
+(	O
+Biospec	O
+)	O
+.	O
+
+Mycobacteria	O
+were	O
+disrupted	O
+using	O
+a	O
+bead	O
+beater	O
+(	O
+Retsch	O
+)	O
+followed	O
+by	O
+a	O
+5	O
+min	O
+centrifugation	O
+at	O
+14	O
+000g	O
+.	O
+
+RNA	O
+contained	O
+in	O
+the	O
+supernatant	O
+was	O
+then	O
+column	O
+-	O
+purified	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+conditions	O
+using	O
+the	O
+RNEasy	O
+mini	O
+kit	O
+(	O
+Qiagen	O
+)	O
+and	O
+quantified	O
+.	O
+
+Quantitative	O
+Real	O
+-	O
+Time	O
+RT	O
+-	O
+PCR	O
+
+In	O
+RNA	O
+samples	O
+DNA	O
+contamination	O
+was	O
+excluded	O
+by	O
+DNAse	O
+I	O
+treatment	O
+(	O
+Ambion	O
+)	O
+.	O
+
+1	O
+micro	O
+g	O
+total	O
+RNA	O
+was	O
+reverse	O
+-	O
+transcribed	O
+using	O
+random	O
+hexamer	O
+primers	O
+(	O
+Ambion	O
+)	O
+and	O
+Superscript	O
+III	O
+reverse	O
+transcriptase	O
+(	O
+Invitrogen	O
+)	O
+.	O
+
+Real	O
+-	O
+time	O
+PCR	O
+was	O
+performed	O
+on	O
+cDNA	O
+using	O
+the	O
+SYBR	O
+green	O
+essay	O
+(	O
+Applied	O
+Biosystems	O
+)	O
+.	O
+
+Reverse	O
+and	O
+forward	O
+primers	O
+used	O
+are	O
+listed	O
+below	O
+in	O
+Table	O
+1	O
+.	O
+
+Fluorescence	O
+was	O
+measured	O
+by	O
+ABIPrism	O
+7300	O
+(	O
+Applied	O
+Biosystems	O
+)	O
+.	O
+
+The	O
+calculated	O
+threshold	O
+cycle	O
+(	O
+Ct	O
+)	O
+value	O
+for	O
+each	O
+gene	O
+of	O
+interest	O
+was	O
+normalized	O
+to	O
+the	O
+Ct	O
+value	O
+for	O
+16S	O
+and	O
+the	O
+fold	O
+expression	O
+was	O
+calculated	O
+using	O
+the	O
+formula	O
+:	O
+fold	O
+change	O
+=	O
+2	O
+-	O
+Delta	O
+.	O
+(	O
+Delta	O
+Ct	O
+)	O
+[	O
+19	O
+]	O
+.	O
+
+Real	O
+-	O
+time	O
+PCR	O
+conditions	O
+include	O
+initial	O
+activation	O
+at	O
+94	O
+degrees	O
+C	O
+for	O
+5	O
+min	O
+,	O
+followed	O
+by	O
+40	O
+cycles	O
+of	O
+denaturation	O
+at	O
+94	O
+degrees	O
+C	O
+for	O
+30	O
+sec	O
+,	O
+annealing	O
+and	O
+extension	O
+at	O
+65	O
+degrees	O
+C	O
+for	O
+1	O
+min	O
+.	O
+
+The	O
+gene	O
+induction	O
+ratios	O
+were	O
+obtained	O
+by	O
+comparing	O
+gene	O
+expression	O
+levels	O
+in	O
+intracellular	O
+bacilli	O
+with	O
+those	O
+of	O
+log	O
+-	O
+phase	O
+in	O
+vitro	O
+-	O
+grown	O
+bacilli	O
+.	O
+
+RNAs	O
+were	O
+isolated	O
+from	O
+two	O
+independent	O
+macrophage	O
+infections	O
+.	O
+
+In	O
+vitro	O
+human	B
+granuloma	O
+formation	O
+
+In	O
+vitro	O
+granulomas	O
+were	O
+obtained	O
+as	O
+previously	O
+described	O
+[	O
+7	O
+]	O
+.	O
+
+Briefly	O
+,	O
+1	O
+x	O
+106	O
+freshly	O
+isolated	O
+Peripheral	O
+Blood	O
+Mononuclear	O
+Cells	O
+(	O
+PBMCs	O
+)	O
+were	O
+incubated	O
+with	O
+1	O
+x	O
+104	O
+viable	O
+M	B
+.	I
+tb	I
+,	O
+or	O
+1	O
+x	O
+103	O
+viable	O
+M	B
+.	I
+smegmatis	I
+or	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+.	O
+
+The	O
+culture	O
+medium	O
+was	O
+RPMI	O
+-	O
+1640	O
++	O
+Glutamax	O
+(	O
+Difco	O
+)	O
+,	O
+containing	O
+7	O
+.	O
+5	O
+%	O
+human	B
+AB	O
+serum	O
+(	O
+Sigma	O
+-	O
+Aldrich	O
+)	O
+.	O
+
+Macrophage	O
+differentiation	O
+
+2	O
+.	O
+5	O
+x	O
+106	O
+PBMCs	O
+prepared	O
+in	O
+RPMI	O
+-	O
+1640	O
++	O
+Glutamax	O
+(	O
+Difco	O
+)	O
+were	O
+plated	O
+over	O
+coverslips	O
+in	O
+24	O
+-	O
+well	O
+plates	O
+.	O
+
+After	O
+2	O
+h	O
+culture	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+cells	O
+were	O
+washed	O
+3	O
+times	O
+with	O
+PBS	O
+and	O
+then	O
+refed	O
+with	O
+RPMI	O
+-	O
+1640	O
++	O
+Glutamax	O
+(	O
+Difco	O
+)	O
+,	O
+containing	O
+7	O
+.	O
+5	O
+%	O
+human	B
+AB	O
+serum	O
+.	O
+
+After	O
+6	O
+days	O
+of	O
+culturing	O
+,	O
+macrophages	O
+were	O
+differentiated	O
+.	O
+
+Respiratory	O
+burst	O
+assay	O
+with	O
+Nitroblue	O
+tetrazolium	O
+(	O
+NBT	O
+)	O
+
+Human	B
+monocyte	O
+derived	O
+macrophages	O
+were	O
+stimulated	O
+with	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+for	O
+2	O
+h	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+washed	O
+and	O
+reincubated	O
+in	O
+mycobacterium	O
+-	O
+free	O
+medium	O
+.	O
+
+After	O
+2	O
+days	O
+of	O
+differentiation	O
+into	O
+FMs	O
+,	O
+macrophages	O
+were	O
+co	O
+-	O
+stained	O
+with	O
+NBT	O
+(	O
+2	O
+mg	O
+/	O
+ml	O
+Sigma	O
+-	O
+Aldrich	O
+)	O
+and	O
+Nile	O
+red	O
+(	O
+Sigma	O
+-	O
+Aldrich	O
+)	O
+for	O
+30	O
+min	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+Stained	O
+cells	O
+were	O
+fixed	O
+and	O
+then	O
+analysed	O
+with	O
+an	O
+inverted	O
+microscope	O
+(	O
+Nikon	O
+TE	O
+300	O
+)	O
+.	O
+
+Phagocytosis	O
+and	O
+Survival	O
+test	O
+
+For	O
+phagocytosis	O
+assays	O
+,	O
+differentiated	O
+macrophages	O
+were	O
+incubated	O
+with	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+mycolic	O
+acids	O
+for	O
+2	O
+days	O
+and	O
+then	O
+infected	O
+with	O
+1	O
+x	O
+108	O
+labeled	O
+mycobacteria	O
+per	O
+well	O
+for	O
+90	O
+min	O
+,	O
+washed	O
+3	O
+times	O
+with	O
+PBS	O
+and	O
+chased	O
+for	O
+3	O
+h	O
+in	O
+fresh	O
+culture	O
+medium	O
+.	O
+
+For	O
+survival	O
+experiments	O
+,	O
+macrophages	O
+were	O
+infected	O
+with	O
+M	B
+.	I
+tuberculosis	I
+-	O
+GFP	O
+(	O
+10	O
+bacteria	O
+/	O
+cell	O
+)	O
+,	O
+washed	O
+3	O
+times	O
+with	O
+PBS	O
+(	O
+Gibco	O
+)	O
+and	O
+re	O
+-	O
+incubated	O
+in	O
+fresh	O
+culture	O
+medium	O
+.	O
+
+At	O
+selected	O
+time	O
+points	O
+thereafter	O
+(	O
+1	O
+,	O
+3	O
+,	O
+6	O
+,	O
+10	O
+and	O
+14	O
+days	O
+)	O
+cells	O
+were	O
+labeled	O
+with	O
+Nile	O
+red	O
+(	O
+Sigma	O
+-	O
+Aldrich	O
+)	O
+,	O
+fixed	O
+and	O
+observed	O
+under	O
+a	O
+confocal	O
+microscope	O
+.	O
+
+The	O
+amount	O
+of	O
+mycobacteria	O
+per	O
+cells	O
+was	O
+evaluated	O
+.	O
+
+(	O
+100	O
+cells	O
+were	O
+analyzed	O
+for	O
+each	O
+time	O
+point	O
+)	O
+.	O
+
+Lipid	O
+body	O
+staining	O
+and	O
+immunostaining	O
+
+Granuloma	O
+cells	O
+were	O
+collected	O
+and	O
+plated	O
+onto	O
+glass	O
+coverslips	O
+with	O
+a	O
+cytospin	O
+(	O
+Thermo	O
+Shandon	O
+)	O
+fixed	O
+for	O
+30	O
+min	O
+in	O
+PBS	O
+-	O
+PFA	O
+4	O
+%	O
+and	O
+stained	O
+with	O
+Oil	O
+red	O
+-	O
+O	O
+(	O
+Sigma	O
+-	O
+Aldrich	O
+)	O
+as	O
+described	O
+[	O
+20	O
+]	O
+.	O
+
+The	O
+slides	O
+were	O
+then	O
+counterstained	O
+with	O
+haematoxylin	O
+(	O
+Dako	O
+Cytomation	O
+)	O
+and	O
+observed	O
+under	O
+an	O
+inverted	O
+microscope	O
+(	O
+Nikon	O
+TE	O
+300	O
+)	O
+.	O
+
+For	O
+fluorescence	O
+analysis	O
+,	O
+granuloma	O
+cells	O
+or	O
+macrophages	O
+were	O
+collected	O
+in	O
+PBS	O
+,	O
+lipid	O
+bodies	O
+were	O
+stained	O
+with	O
+Nile	O
+red	O
+(	O
+Sigma	O
+-	O
+Aldrich	O
+,	O
+0	O
+.	O
+1	O
+micro	O
+g	O
+/	O
+ml	O
+,	O
+from	O
+a	O
+stock	O
+solution	O
+in	O
+methanol	O
+)	O
+for	O
+15	O
+min	O
+washed	O
+with	O
+PBS	O
+,	O
+fixed	O
+for	O
+30	O
+min	O
+in	O
+PBS	O
+-	O
+PFA	O
+4	O
+%	O
+,	O
+mounted	O
+with	O
+the	O
+fluorescent	O
+mounting	O
+medium	O
+(	O
+Dako	O
+Cytomation	O
+)	O
+and	O
+observed	O
+under	O
+a	O
+confocal	O
+microscope	O
+.	O
+
+In	O
+order	O
+to	O
+distinguish	O
+the	O
+lipids	O
+contained	O
+within	O
+lipid	O
+bodies	O
+,	O
+from	O
+those	O
+of	O
+the	O
+cell	O
+membrane	O
+,	O
+we	O
+used	O
+the	O
+fluorescent	O
+emission	O
+spectrum	O
+properties	O
+of	O
+Nile	O
+red	O
+which	O
+depend	O
+upon	O
+the	O
+kind	O
+of	O
+lipid	O
+associated	O
+with	O
+Nile	O
+red	O
+,	O
+i	O
+.	O
+e	O
+.	O
+for	O
+triacylglycerol	O
+:	O
+lambda	O
+max	O
+em	O
+=	O
+590	O
+nm	O
+,	O
+for	O
+phospholipids	O
+:	O
+lambda	O
+max	O
+em	O
+=	O
+640	O
+nm	O
+(	O
+Molecular	O
+Probes	O
+handbook	O
+)	O
+.	O
+
+On	O
+confocal	O
+microscopy	O
+pictures	O
+,	O
+the	O
+phospholipid	O
+background	O
+of	O
+both	O
+macrophages	O
+and	O
+FM	O
+appears	O
+in	O
+red	O
+and	O
+the	O
+triacylglycerol	O
+-	O
+rich	O
+lipid	O
+bodies	O
+appear	O
+in	O
+white	O
+.	O
+
+Cells	O
+were	O
+considered	O
+to	O
+be	O
+positive	O
+for	O
+Nile	O
+red	O
+staining	O
+when	O
+more	O
+than	O
+50	O
+%	O
+of	O
+the	O
+cell	O
+surface	O
+was	O
+stained	O
+(	O
+see	O
+Figure	O
+S2	O
+)	O
+.	O
+
+Mycolic	O
+acid	O
+isolation	O
+
+Bacterial	O
+residues	O
+obtained	O
+after	O
+lipid	O
+extraction	O
+with	O
+organic	O
+solvents	O
+[	O
+17	O
+]	O
+were	O
+saponified	O
+with	O
+a	O
+mixture	O
+of	O
+40	O
+%	O
+KOH	O
+aqueous	O
+solution	O
+and	O
+methoxyethanol	O
+(	O
+1	O
+:	O
+7	O
+,	O
+v	O
+/	O
+v	O
+)	O
+at	O
+110	O
+degrees	O
+C	O
+for	O
+3	O
+hours	O
+in	O
+a	O
+screw	O
+-	O
+capped	O
+tube	O
+.	O
+
+After	O
+acidification	O
+,	O
+fatty	O
+acids	O
+were	O
+extracted	O
+with	O
+diethylether	O
+,	O
+derivatised	O
+into	O
+methyl	O
+esters	O
+with	O
+diazomethane	O
+and	O
+analyzed	O
+by	O
+analytical	O
+thin	O
+-	O
+layer	O
+chromatography	O
+on	O
+silica	O
+Gel	O
+60	O
+(	O
+Silica	O
+Gel	O
+60	O
+Macherey	O
+-	O
+Nagel	O
+)	O
+using	O
+either	O
+dicholoromethane	O
+or	O
+petroleum	O
+ether	O
+/	O
+diethylether	O
+(	O
+9	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+,	O
+five	O
+runs	O
+)	O
+.	O
+
+Visualization	O
+of	O
+lipid	O
+spots	O
+was	O
+performed	O
+by	O
+spraying	O
+the	O
+plates	O
+with	O
+molybdophosphoric	O
+acid	O
+(	O
+10	O
+%	O
+in	O
+ethanol	O
+)	O
+,	O
+followed	O
+by	O
+charring	O
+.	O
+
+Processing	O
+for	O
+electron	O
+microscopy	O
+
+Granulomas	O
+were	O
+fixed	O
+for	O
+1	O
+hour	O
+at	O
+room	O
+temperature	O
+with	O
+2	O
+.	O
+5	O
+%	O
+glutaraldehyde	O
+in	O
+0	O
+.	O
+1	O
+M	O
+cacodylate	O
+buffer	O
+,	O
+pH	O
+7	O
+.	O
+2	O
+,	O
+containing	O
+0	O
+.	O
+1	O
+M	O
+sucrose	O
+,	O
+5	O
+mM	O
+CaCl2	O
+and	O
+5	O
+mM	O
+MgCl2	O
+.	O
+
+After	O
+two	O
+successive	O
+15	O
+-	O
+min	O
+washes	O
+with	O
+the	O
+same	O
+buffer	O
+,	O
+the	O
+granulomas	O
+were	O
+postfixed	O
+for	O
+1	O
+hour	O
+at	O
+RT	O
+with	O
+1	O
+%	O
+osmium	O
+tetroxide	O
+(	O
+Electron	O
+Microscopy	O
+Science	O
+)	O
+in	O
+the	O
+same	O
+buffer	O
+devoid	O
+of	O
+sucrose	O
+.	O
+
+The	O
+granulomas	O
+were	O
+scraped	O
+off	O
+the	O
+culture	O
+dishes	O
+with	O
+a	O
+rubber	O
+policeman	O
+and	O
+concentrated	O
+in	O
+1	O
+%	O
+agarose	O
+in	O
+the	O
+same	O
+buffer	O
+.	O
+
+After	O
+a	O
+one	O
+hour	O
+treatment	O
+at	O
+room	O
+temperature	O
+with	O
+1	O
+%	O
+uranyl	O
+acetate	O
+in	O
+Veronal	O
+buffer	O
+,	O
+the	O
+samples	O
+were	O
+dehydrated	O
+in	O
+a	O
+graded	O
+series	O
+of	O
+ethanol	O
+and	O
+embedded	O
+in	O
+Spurr	O
+resin	O
+.	O
+
+Thin	O
+sections	O
+were	O
+stained	O
+with	O
+uranyl	O
+acetate	O
+and	O
+lead	O
+citrate	O
+.	O
+
+Image	O
+acquisition	O
+in	O
+confocal	O
+microscopy	O
+
+The	O
+images	O
+were	O
+obtained	O
+using	O
+a	O
+Leica	O
+confocal	O
+fluorescence	O
+microscope	O
+(	O
+SP2	O
+)	O
+equipped	O
+with	O
+a	O
+Plan	O
+Apo	O
+40	O
+x	O
+1	O
+.	O
+4	O
+Ph	O
+6	O
+objective	O
+(	O
+Olympus	O
+Optical	O
+)	O
+and	O
+CoolSNAP	O
+-	O
+Pro	O
+CF	O
+digital	O
+camera	O
+in	O
+conjunction	O
+with	O
+Image	O
+-	O
+Pro	O
+Plus	O
+version	O
+4	O
+.	O
+5	O
+.	O
+1	O
+.	O
+3	O
+software	O
+(	O
+Media	O
+Cybernetics	O
+)	O
+.	O
+
+The	O
+images	O
+were	O
+edited	O
+using	O
+Adobe	O
+Photoshop	O
+CS2	O
+9	O
+software	O
+(	O
+Adobe	O
+Systems	O
+)	O
+.	O
+
+Results	O
+
+Foamy	O
+macrophages	O
+are	O
+strongly	O
+associated	O
+with	O
+necrotic	O
+lesions	O
+and	O
+often	O
+contain	O
+M	B
+.	I
+tuberculosis	I
+
+We	O
+analyzed	O
+lymph	O
+node	O
+biopsies	O
+from	O
+10	O
+tuberculous	O
+patients	B
+as	O
+a	O
+first	O
+step	O
+for	O
+evaluating	O
+the	O
+role	O
+of	O
+FMs	O
+within	O
+tuberculous	O
+granulomas	O
+.	O
+
+A	O
+section	O
+through	O
+a	O
+representative	O
+biopsy	O
+is	O
+shown	O
+in	O
+Figure	O
+1	O
+.	O
+
+Well	O
+-	O
+circumscribed	O
+and	O
+-	O
+differentiated	O
+granulomatous	O
+structures	O
+were	O
+observed	O
+in	O
+all	O
+the	O
+samples	O
+(	O
+Figure	O
+1A	O
+)	O
+.	O
+
+Classically	O
+,	O
+lesions	O
+display	O
+a	O
+necrotic	O
+center	O
+(	O
+N	O
+)	O
+,	O
+an	O
+interface	O
+area	O
+between	O
+the	O
+necrotic	O
+center	O
+and	O
+the	O
+histiocytes	O
+(	O
+I	O
+)	O
+,	O
+and	O
+some	O
+peripheral	O
+granulomas	O
+(	O
+G	O
+)	O
+.	O
+
+Only	O
+seven	O
+out	O
+of	O
+ten	O
+patients	B
+presented	O
+lesions	O
+displaying	O
+central	O
+necrosis	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Staining	O
+of	O
+the	O
+histology	O
+samples	O
+with	O
+Oil	O
+red	O
+-	O
+O	O
+,	O
+a	O
+classic	O
+lipid	O
+stain	O
+,	O
+confirmed	O
+the	O
+presence	O
+of	O
+FMs	O
+within	O
+the	O
+granulomatous	O
+structures	O
+in	O
+six	O
+out	O
+of	O
+seven	O
+samples	O
+presenting	O
+necrosis	O
+(	O
+Figure	O
+1B	O
+)	O
+,	O
+whereas	O
+no	O
+FMs	O
+were	O
+found	O
+in	O
+the	O
+three	O
+non	O
+-	O
+necrotic	O
+lesions	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Noteworthy	O
+,	O
+in	O
+samples	O
+with	O
+necrotic	O
+areas	O
+,	O
+FMs	O
+were	O
+always	O
+found	O
+in	O
+the	O
+interface	O
+region	O
+flanking	O
+the	O
+central	O
+necrosis	O
+(	O
+Figure	O
+1B	O
+)	O
+.	O
+
+These	O
+observations	O
+firstly	O
+confirmed	O
+the	O
+presence	O
+of	O
+FMs	O
+in	O
+most	O
+TB	O
+patients	B
+'	O
+lesions	O
+thereby	O
+suggesting	O
+that	O
+these	O
+cells	O
+play	O
+an	O
+important	O
+role	O
+in	O
+the	O
+formation	O
+/	O
+maintenance	O
+of	O
+such	O
+lesions	O
+.	O
+
+Second	O
+,	O
+FMs	O
+seem	O
+to	O
+be	O
+associated	O
+with	O
+necrosis	O
+,	O
+which	O
+is	O
+a	O
+hallmark	O
+of	O
+TB	O
+lesions	O
+,	O
+since	O
+they	O
+were	O
+observed	O
+only	O
+in	O
+lesions	O
+with	O
+a	O
+necrotic	O
+center	O
+and	O
+preferentially	O
+located	O
+around	O
+the	O
+necrotic	O
+area	O
+.	O
+
+Interestingly	O
+,	O
+staining	O
+,	O
+in	O
+parallel	O
+,	O
+of	O
+serial	O
+thin	O
+sections	O
+from	O
+a	O
+patient	B
+'	O
+s	O
+lesion	O
+biopsy	O
+with	O
+Oil	O
+red	O
+-	O
+O	O
+(	O
+Figure	O
+1C	O
+)	O
+and	O
+Ziehl	O
+Nielsen	O
+(	O
+Figure	O
+1D	O
+)	O
+,	O
+showed	O
+that	O
+most	O
+of	O
+the	O
+bacilli	O
+(	O
+arrow	O
+)	O
+were	O
+located	O
+in	O
+the	O
+same	O
+area	O
+as	O
+FMs	O
+,	O
+thus	O
+suggesting	O
+a	O
+strong	O
+association	O
+between	O
+the	O
+persisting	O
+tubercle	O
+bacilli	O
+and	O
+FMs	O
+within	O
+granulomas	O
+.	O
+
+M	B
+.	I
+tuberculosis	I
+induces	O
+the	O
+formation	O
+of	O
+FMs	O
+within	O
+in	O
+vitro	O
+human	B
+tuberculous	O
+granulomas	O
+
+To	O
+further	O
+characterize	O
+the	O
+role	O
+of	O
+FMs	O
+in	O
+the	O
+granulomatous	O
+response	O
+,	O
+we	O
+assessed	O
+whether	O
+FM	O
+formation	O
+in	O
+granulomatous	O
+structures	O
+was	O
+triggered	O
+only	O
+by	O
+pathogenic	O
+mycobacterial	O
+species	O
+(	O
+M	B
+.	I
+tb	I
+)	O
+,	O
+or	O
+by	O
+low	O
+virulent	O
+ones	O
+(	O
+M	B
+.	I
+smegmatis	I
+)	O
+as	O
+well	O
+.	O
+
+PBMCs	O
+from	O
+non	O
+-	O
+tuberculous	O
+control	O
+individuals	O
+were	O
+infected	O
+with	O
+M	B
+.	I
+tb	I
+or	O
+M	B
+.	I
+smegmatis	I
+,	O
+following	O
+the	O
+procedure	O
+previously	O
+described	O
+for	O
+the	O
+induction	O
+of	O
+granulomatous	O
+structures	O
+(	O
+[	O
+7	O
+]	O
+,	O
+[	O
+9	O
+]	O
+and	O
+Figure	O
+S1	O
+)	O
+.	O
+
+Granuloma	O
+cells	O
+collected	O
+at	O
+days	O
+3	O
+and	O
+11	O
+were	O
+stained	O
+with	O
+Oil	O
+red	O
+-	O
+O	O
+to	O
+visualize	O
+the	O
+lipid	O
+droplets	O
+within	O
+FMs	O
+under	O
+the	O
+light	O
+microscope	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+At	O
+day	O
+3	O
+,	O
+several	O
+M	B
+.	I
+tb	I
+-	O
+induced	O
+granuloma	O
+cells	O
+already	O
+showed	O
+lipid	O
+bodies	O
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+the	O
+cells	O
+collected	O
+from	O
+M	B
+.	I
+smegmatis	I
+-	O
+induced	O
+granulomas	O
+were	O
+seldom	O
+(	O
+5	O
+%	O
+)	O
+positively	O
+stained	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+M	B
+.	I
+avium	I
+induced	O
+FM	O
+formation	O
+in	O
+a	O
+similar	O
+way	O
+to	O
+M	B
+.	I
+tb	I
+(	O
+not	O
+shown	O
+)	O
+.	O
+
+By	O
+day	O
+11	O
+,	O
+the	O
+amount	O
+of	O
+positively	O
+stained	O
+cells	O
+had	O
+increased	O
+in	O
+M	B
+.	I
+tb	I
+-	O
+induced	O
+granulomas	O
+,	O
+but	O
+not	O
+in	O
+M	B
+.	I
+smegmatis	I
+-	O
+induced	O
+ones	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+number	O
+of	O
+lipid	O
+bodies	O
+per	O
+cell	O
+increased	O
+dramatically	O
+with	O
+time	O
+,	O
+as	O
+depited	O
+in	O
+the	O
+enlarged	O
+views	O
+(	O
+Figures	O
+2A	O
+,	O
+C	O
+)	O
+.	O
+
+The	O
+quantitative	O
+evaluation	O
+of	O
+the	O
+percentage	O
+of	O
+FMs	O
+within	O
+granulomas	O
+induced	O
+by	O
+both	O
+strains	O
+confirmed	O
+the	O
+differences	O
+observed	O
+under	O
+the	O
+light	O
+microscope	O
+,	O
+and	O
+showed	O
+a	O
+seven	O
+-	O
+fold	O
+difference	O
+(	O
+44	O
+%	O
+vs	O
+6	O
+%	O
+respectively	O
+)	O
+between	O
+M	B
+.	I
+tb	I
+and	O
+M	B
+.	I
+smegmatis	I
+in	O
+terms	O
+of	O
+their	O
+ability	O
+to	O
+induce	O
+FM	O
+formation	O
+(	O
+Figure	O
+2D	O
+)	O
+.	O
+
+Our	O
+results	O
+therefore	O
+show	O
+that	O
+virulent	O
+species	O
+such	O
+as	O
+M	B
+.	I
+tb	I
+and	O
+M	B
+.	I
+avium	I
+,	O
+contrary	O
+to	O
+poorly	O
+or	O
+avirulent	O
+ones	O
+such	O
+as	O
+M	B
+.	I
+smegmatis	I
+,	O
+are	O
+able	O
+to	O
+induce	O
+the	O
+formation	O
+of	O
+FMs	O
+within	O
+our	O
+experimental	O
+model	O
+.	O
+
+Oxygenated	O
+mycolic	O
+acids	O
+induce	O
+the	O
+maturation	O
+of	O
+macrophages	O
+into	O
+FMs	O
+
+Mycolic	O
+acids	O
+from	O
+M	B
+.	I
+tb	I
+incorporated	O
+into	O
+liposomes	O
+were	O
+recently	O
+shown	O
+to	O
+trigger	O
+the	O
+differentiation	O
+of	O
+mice	B
+peritoneal	O
+macrophages	O
+into	O
+foamy	O
+-	O
+like	O
+cells	O
+[	O
+21	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+both	O
+M	B
+.	I
+tb	I
+and	O
+M	B
+.	I
+avium	I
+,	O
+which	O
+induce	O
+FM	O
+formation	O
+,	O
+express	O
+a	O
+family	O
+of	O
+oxygenated	O
+mycolic	O
+acids	O
+,	O
+especially	O
+ketomycolic	O
+acids	O
+,	O
+which	O
+are	O
+not	O
+produced	O
+by	O
+M	B
+.	I
+smegmatis	I
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+In	O
+this	O
+context	O
+,	O
+inactivation	O
+of	O
+the	O
+M	B
+.	I
+tb	I
+hma	O
+gene	O
+(	O
+mmaA4	O
+-	O
+Rv0642c	O
+)	O
+was	O
+shown	O
+to	O
+abolish	O
+the	O
+synthesis	O
+of	O
+oxygenated	O
+keto	O
+-	O
+and	O
+hydroxyl	O
+-	O
+mycolic	O
+acid	O
+in	O
+the	O
+mutant	O
+strain	O
+[	O
+17	O
+]	O
+.	O
+
+Conversely	O
+,	O
+transforming	O
+M	B
+.	I
+smegmatis	I
+with	O
+the	O
+hma	O
+gene	O
+induced	O
+the	O
+production	O
+of	O
+both	O
+keto	O
+-	O
+and	O
+hydroxyl	O
+-	O
+mycolic	O
+acids	O
+[	O
+22	O
+]	O
+,	O
+(	O
+Figures	O
+3B	O
+,	O
+C	O
+)	O
+.	O
+
+In	O
+the	O
+light	O
+of	O
+both	O
+data	O
+,	O
+we	O
+anticipated	O
+that	O
+oxygenated	O
+mycolic	O
+acids	O
+specifically	O
+produced	O
+by	O
+M	B
+.	I
+tb	I
+and	O
+M	B
+.	I
+avium	I
+,	O
+under	O
+the	O
+control	O
+of	O
+hma	O
+,	O
+are	O
+responsible	O
+for	O
+FM	O
+formation	O
+within	O
+human	B
+granulomas	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+we	O
+compared	O
+FM	O
+formation	O
+after	O
+infection	O
+of	O
+PBMCs	O
+with	O
+either	O
+the	O
+wild	O
+-	O
+type	O
+,	O
+or	O
+the	O
+hma	O
+-	O
+expressing	O
+M	B
+.	I
+smegmatis	I
+strain	O
+(	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+)	O
+.	O
+
+Granulomas	O
+cells	O
+were	O
+collected	O
+3	O
+days	O
+later	O
+and	O
+stained	O
+with	O
+Oil	O
+red	O
+-	O
+O	O
+to	O
+visualize	O
+lipid	O
+bodies	O
+.	O
+
+Wild	O
+-	O
+type	O
+M	B
+.	I
+smegmatis	I
+-	O
+induced	O
+granulomas	O
+displayed	O
+only	O
+5	O
+.	O
+5	O
+%	O
+of	O
+FM	O
+,	O
+whereas	O
+the	O
+hma	O
+gene	O
+-	O
+expressing	O
+strain	O
+induced	O
+granulomas	O
+bearing	O
+a	O
+majority	O
+(	O
+67	O
+%	O
+)	O
+of	O
+brightly	O
+stained	O
+Oil	O
+red	O
+-	O
+O	O
+positive	O
+cells	O
+(	O
+Figures	O
+4A	O
+,	O
+B	O
+,	O
+C	O
+)	O
+.	O
+
+Induction	O
+of	O
+FM	O
+formation	O
+was	O
+even	O
+greater	O
+if	O
+isolated	O
+macrophages	O
+were	O
+directly	O
+infected	O
+with	O
+either	O
+strain	O
+.	O
+
+After	O
+only	O
+4	O
+hours	O
+of	O
+infection	O
+,	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+had	O
+already	O
+transformed	O
+64	O
+%	O
+of	O
+the	O
+infected	O
+macrophages	O
+into	O
+lipid	O
+body	O
+-	O
+positive	O
+cells	O
+(	O
+see	O
+Figure	O
+S2	O
+for	O
+Nile	O
+red	O
+positive	O
+cells	O
+)	O
+,	O
+whereas	O
+only	O
+9	O
+%	O
+of	O
+the	O
+cells	O
+contained	O
+lipid	O
+bodies	O
+after	O
+infection	O
+with	O
+the	O
+wild	O
+-	O
+type	O
+strain	O
+(	O
+Figures	O
+4D	O
+,	O
+E	O
+,	O
+F	O
+)	O
+.	O
+
+To	O
+confirm	O
+the	O
+specific	O
+role	O
+of	O
+hma	O
+-	O
+dependent	O
+oxygenated	O
+mycolic	O
+acids	O
+in	O
+FM	O
+formation	O
+,	O
+and	O
+to	O
+rule	O
+out	O
+a	O
+possible	O
+combined	O
+effect	O
+of	O
+oxygenated	O
+mycolic	O
+-	O
+acids	O
+with	O
+other	O
+mycobacterial	O
+components	O
+,	O
+mycolic	O
+acids	O
+isolated	O
+from	O
+wild	O
+-	O
+type	O
+M	B
+.	I
+smegmatis	I
+or	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+were	O
+incubated	O
+with	O
+isolated	O
+macrophages	O
+.	O
+
+With	O
+mycolic	O
+acids	O
+isolated	O
+from	O
+the	O
+wild	O
+-	O
+type	O
+strain	O
+,	O
+only	O
+13	O
+%	O
+of	O
+the	O
+macrophages	O
+were	O
+transformed	O
+into	O
+FM	O
+whereas	O
+66	O
+%	O
+of	O
+the	O
+macrophages	O
+incubated	O
+with	O
+mycolic	O
+acids	O
+isolated	O
+from	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+were	O
+strongly	O
+stained	O
+for	O
+lipid	O
+bodies	O
+(	O
+Figures	O
+4G	O
+,	O
+H	O
+,	O
+I	O
+)	O
+.	O
+
+These	O
+results	O
+therefore	O
+indicate	O
+that	O
+oxygenated	O
+mycolic	O
+acids	O
+play	O
+a	O
+leading	O
+role	O
+in	O
+M	B
+.	I
+tb	I
+-	O
+induced	O
+FM	O
+formation	O
+.	O
+
+The	O
+phagocytic	O
+and	O
+bactericidal	O
+activities	O
+are	O
+arrested	O
+in	O
+FMs	O
+
+To	O
+assess	O
+the	O
+function	O
+of	O
+granuloma	O
+FM	O
+,	O
+we	O
+first	O
+evaluated	O
+the	O
+ability	O
+of	O
+such	O
+cells	O
+to	O
+mediate	O
+phagocytosis	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+macrophages	O
+isolated	O
+from	O
+PBMCs	O
+were	O
+exposed	O
+to	O
+M	B
+.	I
+smegmatis	I
+/	O
+hma	O
+-	O
+derived	O
+mycolic	O
+acids	O
+to	O
+induce	O
+FM	O
+formation	O
+.	O
+
+Two	O
+days	O
+later	O
+,	O
+the	O
+cell	O
+population	O
+contained	O
+a	O
+mixture	O
+of	O
+FM	O
+(	O
+50	O
+-	O
+70	O
+%	O
+)	O
+and	O
+macrophages	O
+(	O
+30	O
+-	O
+50	O
+%	O
+)	O
+,	O
+as	O
+assessed	O
+by	O
+Nile	O
+red	O
+staining	O
+(	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+mixed	O
+cell	O
+population	O
+was	O
+infected	O
+with	O
+FITC	O
+-	O
+labelled	O
+M	B
+.	I
+smegmatis	I
+.	O
+
+Intracellular	O
+bacilli	O
+were	O
+found	O
+only	O
+within	O
+Nile	O
+red	O
+-	O
+negative	O
+macrophages	O
+thereby	O
+indicating	O
+that	O
+FMs	O
+are	O
+unable	O
+to	O
+ingest	O
+bacteria	O
+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+This	O
+result	O
+was	O
+reproduced	O
+using	O
+other	O
+mycobacterial	O
+strains	O
+,	O
+such	O
+as	O
+M	B
+.	I
+tb	I
+and	O
+M	B
+.	I
+bovis	I
+BCG	I
+,	O
+for	O
+infection	O
+(	O
+not	O
+shown	O
+)	O
+.	O
+
+These	O
+results	O
+further	O
+suggest	O
+that	O
+the	O
+bacilli	O
+found	O
+in	O
+granuloma	O
+FMs	O
+were	O
+internalized	O
+by	O
+macrophages	O
+prior	O
+to	O
+their	O
+transformation	O
+into	O
+FMs	O
+.	O
+
+To	O
+assess	O
+whether	O
+FMs	O
+are	O
+able	O
+to	O
+develop	O
+a	O
+respiratory	O
+burst	O
+,	O
+which	O
+is	O
+a	O
+major	O
+intracellular	O
+bactericidal	O
+activity	O
+,	O
+the	O
+ability	O
+of	O
+Nile	O
+red	O
+positive	O
+cells	O
+(	O
+i	O
+.	O
+e	O
+.	O
+FMs	O
+)	O
+to	O
+mediate	O
+NBT	O
+reduction	O
+was	O
+determined	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+5D	O
+,	O
+only	O
+8	O
+%	O
+of	O
+the	O
+NBT	O
+-	O
+positive	O
+cells	O
+(	O
+Figure	O
+5B	O
+)	O
+were	O
+Nile	O
+red	O
+positive	O
+FMs	O
+(	O
+Figure	O
+5C	O
+)	O
+.	O
+
+This	O
+strongly	O
+suggests	O
+that	O
+once	O
+macrophages	O
+have	O
+differentiated	O
+into	O
+FMs	O
+,	O
+they	O
+lose	O
+the	O
+ability	O
+to	O
+mediate	O
+intracellular	O
+bactericidal	O
+activity	O
+.	O
+
+We	O
+postulate	O
+that	O
+FMs	O
+could	O
+,	O
+therefore	O
+,	O
+form	O
+a	O
+secure	O
+reservoir	O
+for	O
+the	O
+tubercle	O
+bacilli	O
+.	O
+
+M	B
+.	I
+tuberculosis	I
+persists	O
+in	O
+a	O
+dormant	O
+non	O
+-	O
+replicative	O
+state	O
+in	O
+FMs	O
+
+To	O
+evaluate	O
+the	O
+validity	O
+of	O
+the	O
+above	O
+hypothesis	O
+,	O
+we	O
+analyzed	O
+the	O
+ability	O
+of	O
+M	B
+.	I
+tb	I
+to	O
+replicate	O
+within	O
+FMs	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+isolated	O
+macrophages	O
+were	O
+infected	O
+with	O
+M	B
+.	I
+tb	I
+.	O
+
+At	O
+selected	O
+intervals	O
+post	O
+-	O
+infection	O
+,	O
+the	O
+amount	O
+of	O
+bacilli	O
+per	O
+cell	O
+was	O
+compared	O
+in	O
+both	O
+non	O
+-	O
+differentiated	O
+macrophages	O
+and	O
+FMs	O
+(	O
+Figure	O
+5E	O
+)	O
+.	O
+
+Until	O
+day	O
+6	O
+,	O
+M	B
+.	I
+tb	I
+replicated	O
+in	O
+a	O
+similar	O
+fashion	O
+in	O
+both	O
+cell	O
+types	O
+.	O
+
+In	O
+contrast	O
+,	O
+after	O
+day	O
+6	O
+post	O
+-	O
+infection	O
+,	O
+the	O
+amount	O
+of	O
+bacilli	O
+remained	O
+stationary	O
+in	O
+FMs	O
+,	O
+whereas	O
+it	O
+continued	O
+to	O
+increase	O
+in	O
+macrophages	O
+.	O
+
+It	O
+is	O
+interesting	O
+to	O
+note	O
+that	O
+arrest	O
+of	O
+bacterial	O
+replication	O
+coincided	O
+with	O
+completion	O
+of	O
+macrophage	O
+differentiation	O
+into	O
+FM	O
+,	O
+i	O
+.	O
+e	O
+.	O
+starting	O
+from	O
+day	O
+3	O
+post	O
+-	O
+infection	O
+.	O
+
+Our	O
+data	O
+suggest	O
+,	O
+that	O
+the	O
+bacilli	O
+found	O
+in	O
+granuloma	O
+FMs	O
+were	O
+internalized	O
+by	O
+macrophages	O
+prior	O
+to	O
+their	O
+differentiation	O
+into	O
+FMs	O
+and	O
+also	O
+that	O
+bacilli	O
+can	O
+terminate	O
+their	O
+replication	O
+cycle	O
+while	O
+macrophages	O
+are	O
+being	O
+transformed	O
+into	O
+FM	O
+,	O
+but	O
+that	O
+replication	O
+comes	O
+to	O
+a	O
+halt	O
+as	O
+soon	O
+as	O
+the	O
+maturation	O
+process	O
+is	O
+complete	O
+.	O
+
+We	O
+next	O
+determined	O
+whether	O
+the	O
+non	O
+-	O
+replicative	O
+bacilli	O
+observed	O
+in	O
+FMs	O
+were	O
+still	O
+alive	O
+.	O
+
+For	O
+this	O
+purpose	O
+,	O
+we	O
+analyzed	O
+the	O
+expression	O
+of	O
+a	O
+series	O
+of	O
+genes	O
+known	O
+to	O
+be	O
+up	O
+-	O
+regulated	O
+when	O
+bacilli	O
+are	O
+in	O
+a	O
+persistent	O
+non	O
+-	O
+replicating	O
+state	O
+[	O
+23	O
+]	O
+,	O
+[	O
+24	O
+]	O
+.	O
+
+RNA	O
+was	O
+,	O
+therefore	O
+,	O
+prepared	O
+from	O
+both	O
+in	O
+vitro	O
+-	O
+grown	O
+M	B
+.	I
+tb	I
+and	O
+intracellular	O
+bacilli	O
+at	O
+day	O
+6	O
+and	O
+12	O
+post	O
+-	O
+infection	O
+.	O
+
+The	O
+respective	O
+amounts	O
+of	O
+RNA	O
+corresponding	O
+to	O
+isocitrate	O
+lyase	O
+,	O
+alpha	O
+-	O
+cristallin	O
+,	O
+a	O
+very	O
+hypothetical	O
+7	O
+.	O
+6	O
+kDa	O
+protein	O
+,	O
+CHP	O
+and	O
+DosR	O
+proteins	O
+were	O
+then	O
+quantified	O
+by	O
+RT	O
+-	O
+PCR	O
+.	O
+
+As	O
+shown	O
+in	O
+Table	O
+3	O
+,	O
+the	O
+dormancy	O
+genes	O
+were	O
+all	O
+strongly	O
+up	O
+-	O
+regulated	O
+in	O
+intracellular	O
+bacilli	O
+at	O
+day	O
+12	O
+post	O
+-	O
+infection	O
+.	O
+
+These	O
+results	O
+further	O
+demonstrate	O
+that	O
+the	O
+bacilli	O
+are	O
+not	O
+killed	O
+in	O
+FMs	O
+,	O
+but	O
+rather	O
+persist	O
+in	O
+a	O
+dormant	O
+,	O
+and	O
+therefore	O
+non	O
+-	O
+replicative	O
+stage	O
+[	O
+25	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+dormancy	O
+genes	O
+were	O
+not	O
+as	O
+strongly	O
+expressed	O
+at	O
+day	O
+6	O
+,	O
+time	O
+at	O
+which	O
+bacteria	O
+were	O
+still	O
+able	O
+to	O
+replicate	O
+in	O
+macrophages	O
+undergoing	O
+differentiation	O
+into	O
+FMs	O
+.	O
+
+Characterization	O
+of	O
+M	B
+.	I
+tb	I
+survival	O
+within	O
+FMs	O
+and	O
+interaction	O
+with	O
+lipid	O
+bodies	O
+
+To	O
+gain	O
+further	O
+insight	O
+into	O
+the	O
+morphological	O
+appearance	O
+of	O
+M	B
+.	I
+tb	I
+within	O
+FM	O
+and	O
+into	O
+the	O
+interactions	O
+between	O
+FM	O
+lipid	O
+bodies	O
+(	O
+LB	O
+)	O
+and	O
+M	B
+.	I
+tb	I
+-	O
+containing	O
+phagosomes	O
+,	O
+granulomas	O
+were	O
+fixed	O
+and	O
+processed	O
+for	O
+conventional	O
+electron	O
+microscopy	O
+at	O
+days	O
+3	O
+and	O
+11	O
+post	O
+-	O
+infection	O
+.	O
+
+Whatever	O
+the	O
+time	O
+point	O
+at	O
+which	O
+granuloma	O
+cells	O
+were	O
+observed	O
+,	O
+bacteria	O
+were	O
+all	O
+enclosed	O
+in	O
+phagosomes	O
+,	O
+most	O
+of	O
+which	O
+contained	O
+a	O
+single	O
+bacterium	O
+.	O
+
+None	O
+of	O
+them	O
+(	O
+over	O
+a	O
+thousand	O
+which	O
+were	O
+examined	O
+under	O
+the	O
+electron	O
+microscope	O
+)	O
+were	O
+free	O
+in	O
+the	O
+cytoplasm	O
+and	O
+only	O
+one	O
+was	O
+enclosed	O
+in	O
+a	O
+classical	O
+autophagic	O
+vacuole	O
+.	O
+
+At	O
+day	O
+3	O
+post	O
+-	O
+infection	O
+,	O
+FMs	O
+profiles	O
+(	O
+thin	O
+sections	O
+)	O
+were	O
+scarce	O
+,	O
+representing	O
+at	O
+most	O
+9	O
+%	O
+of	O
+the	O
+total	O
+population	O
+of	O
+macrophage	O
+profiles	O
+observed	O
+under	O
+the	O
+electron	O
+microscope	O
+(	O
+Figure	O
+6A	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+86	O
+%	O
+of	O
+the	O
+FM	O
+profiles	O
+displayed	O
+at	O
+most	O
+5	O
+small	O
+LBs	O
+(	O
+Figure	O
+6B	O
+)	O
+.	O
+
+At	O
+this	O
+stage	O
+of	O
+granuloma	O
+formation	O
+,	O
+bacteria	O
+were	O
+infrequent	O
+in	O
+FM	O
+,	O
+but	O
+were	O
+found	O
+in	O
+other	O
+types	O
+of	O
+macrophages	O
+.	O
+
+One	O
+of	O
+these	O
+displayed	O
+large	O
+numbers	O
+of	O
+vacuoles	O
+containing	O
+flocculent	O
+material	O
+and	O
+often	O
+one	O
+or	O
+two	O
+LBs	O
+.	O
+
+Over	O
+95	O
+%	O
+of	O
+the	O
+bacteria	O
+located	O
+in	O
+the	O
+different	O
+granuloma	O
+macrophages	O
+were	O
+morphologically	O
+intact	O
+,	O
+and	O
+therefore	O
+alive	O
+[	O
+26	O
+]	O
+.	O
+
+Intact	O
+bacteria	O
+present	O
+no	O
+breaks	O
+in	O
+the	O
+cell	O
+wall	O
+or	O
+cytoplasmic	O
+membrane	O
+and	O
+their	O
+cytoplasm	O
+has	O
+preserved	O
+its	O
+ultrastructural	O
+organization	O
+and	O
+electron	O
+opacity	O
+.	O
+
+Furthermore	O
+,	O
+they	O
+display	O
+no	O
+electron	O
+translucent	O
+intracytoplasmic	O
+lipid	O
+inclusions	O
+(	O
+ILI	O
+)	O
+.	O
+
+Bacteria	O
+were	O
+also	O
+observed	O
+in	O
+between	O
+cells	O
+,	O
+probably	O
+as	O
+a	O
+result	O
+of	O
+cell	O
+lysis	O
+within	O
+granulomas	O
+.	O
+
+These	O
+bacteria	O
+were	O
+also	O
+morphologically	O
+intact	O
+and	O
+devoid	O
+of	O
+ILI	O
+(	O
+not	O
+shown	O
+)	O
+.	O
+
+At	O
+day	O
+11	O
+post	O
+-	O
+infection	O
+,	O
+M	B
+.	I
+tb	I
+-	O
+containing	O
+macrophages	O
+displaying	O
+large	O
+numbers	O
+of	O
+vacuoles	O
+with	O
+flocculent	O
+material	O
+were	O
+less	O
+frequently	O
+observed	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+amount	O
+of	O
+such	O
+vacuoles	O
+had	O
+strongly	O
+decreased	O
+in	O
+most	O
+of	O
+these	O
+cells	O
+while	O
+the	O
+number	O
+of	O
+LBs	O
+had	O
+increased	O
+.	O
+
+The	O
+percentage	O
+of	O
+FM	O
+had	O
+increased	O
+to	O
+reach	O
+41	O
+%	O
+of	O
+the	O
+total	O
+population	O
+of	O
+macrophage	O
+profiles	O
+within	O
+the	O
+granulomas	O
+(	O
+Figure	O
+6A	O
+)	O
+.	O
+
+From	O
+these	O
+observations	O
+,	O
+it	O
+is	O
+tempting	O
+to	O
+assume	O
+that	O
+the	O
+highly	O
+vesiculated	O
+macrophages	O
+give	O
+rise	O
+to	O
+FMs	O
+.	O
+
+Within	O
+FMs	O
+,	O
+the	O
+size	O
+and	O
+amount	O
+of	O
+LBs	O
+had	O
+also	O
+increased	O
+with	O
+time	O
+since	O
+48	O
+%	O
+of	O
+the	O
+FM	O
+profiles	O
+now	O
+displayed	O
+more	O
+than	O
+5	O
+LB	O
+per	O
+FM	O
+thin	O
+section	O
+(	O
+Figure	O
+6B	O
+)	O
+,	O
+randomly	O
+distributed	O
+within	O
+the	O
+cells	O
+(	O
+Figure	O
+6C	O
+)	O
+.	O
+
+About	O
+30	O
+%	O
+of	O
+the	O
+FM	O
+profiles	O
+displayed	O
+between	O
+1	O
+and	O
+20	O
+bacteria	O
+,	O
+which	O
+were	O
+morphologically	O
+intact	O
+and	O
+enclosed	O
+within	O
+phagosomes	O
+(	O
+Figure	O
+6C	O
+,	O
+enlarged	O
+view	O
+)	O
+.	O
+
+The	O
+interaction	O
+between	O
+these	O
+bacteria	O
+and	O
+the	O
+cellular	O
+LBs	O
+was	O
+next	O
+examined	O
+at	O
+day	O
+11	O
+.	O
+
+Sixty	O
+percent	O
+of	O
+the	O
+bacilli	O
+were	O
+scattered	O
+throughout	O
+the	O
+FMs	O
+and	O
+displayed	O
+no	O
+obvious	O
+signs	O
+of	O
+interaction	O
+with	O
+the	O
+cellular	O
+LBs	O
+.	O
+
+A	O
+small	O
+fraction	O
+of	O
+the	O
+bacteria	O
+(	O
+21	O
+%	O
+)	O
+,	O
+however	O
+,	O
+were	O
+observed	O
+in	O
+the	O
+close	O
+vicinity	O
+of	O
+cellular	O
+LBs	O
+.	O
+
+The	O
+membrane	O
+of	O
+the	O
+phagosomes	O
+in	O
+which	O
+they	O
+were	O
+enclosed	O
+clearly	O
+interacted	O
+with	O
+cellular	O
+LBs	O
+(	O
+Figures	O
+6C	O
+,	O
+7A	O
+,	O
+7B	O
+,	O
+arrows	O
+)	O
+and	O
+became	O
+tightly	O
+apposed	O
+to	O
+an	O
+increasingly	O
+larger	O
+surface	O
+area	O
+of	O
+the	O
+LB	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+the	O
+phagosomes	O
+started	O
+to	O
+surround	O
+LBs	O
+in	O
+a	O
+zippering	O
+fashion	O
+(	O
+Figures	O
+7E	O
+,	O
+F	O
+)	O
+.	O
+
+Ultimately	O
+,	O
+bacilli	O
+(	O
+19	O
+%	O
+)	O
+were	O
+translocated	O
+to	O
+cellular	O
+LBs	O
+(	O
+Figure	O
+7C	O
+)	O
+.	O
+
+From	O
+these	O
+observations	O
+,	O
+it	O
+is	O
+tempting	O
+to	O
+assume	O
+that	O
+M	B
+.	I
+tb	I
+-	O
+containing	O
+phagosomes	O
+engulf	O
+cellular	O
+LBs	O
+rather	O
+than	O
+fusing	O
+with	O
+them	O
+.	O
+
+This	O
+process	O
+,	O
+which	O
+is	O
+reminiscent	O
+of	O
+autophagy	O
+,	O
+resulted	O
+in	O
+the	O
+transfer	O
+of	O
+free	O
+bacteria	O
+into	O
+the	O
+lumen	O
+of	O
+cellular	O
+LBs	O
+(	O
+Figure	O
+7C	O
+)	O
+,	O
+some	O
+of	O
+which	O
+displayed	O
+up	O
+to	O
+21	O
+bacteria	O
+(	O
+Figure	O
+7G	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+only	O
+altered	O
+M	B
+.	I
+tb	I
+found	O
+within	O
+FM	O
+lipid	O
+bodies	O
+exhibited	O
+electron	O
+translucent	O
+ILIs	O
+(	O
+Figures	O
+7D	O
+,	O
+G	O
+)	O
+,	O
+thereby	O
+suggesting	O
+that	O
+they	O
+are	O
+able	O
+to	O
+accumulate	O
+host	O
+cell	O
+lipids	O
+.	O
+
+In	O
+previous	O
+work	O
+,	O
+the	O
+term	O
+altered	O
+bacteria	O
+had	O
+been	O
+used	O
+to	O
+define	O
+live	O
+bacteria	O
+that	O
+had	O
+acquired	O
+ILIs	O
+[	O
+26	O
+]	O
+.	O
+
+Since	O
+the	O
+presence	O
+of	O
+ILIs	O
+within	O
+the	O
+cytoplasm	O
+of	O
+M	B
+.	I
+tb	I
+is	O
+typical	O
+for	O
+non	O
+-	O
+replicating	O
+bacteria	O
+in	O
+a	O
+state	O
+of	O
+dormancy	O
+[	O
+27	O
+]	O
+,	O
+this	O
+further	O
+confirms	O
+that	O
+these	O
+bacteria	O
+are	O
+dormant	O
+.	O
+
+Discussion	O
+
+Studies	O
+carried	O
+out	O
+several	O
+decades	O
+ago	O
+suggested	O
+that	O
+postprimary	O
+tuberculosis	O
+starts	O
+as	O
+a	O
+lipid	O
+pneumonia	O
+[	O
+28	O
+]	O
+,	O
+[	O
+29	O
+]	O
+.	O
+
+Indeed	O
+,	O
+following	O
+a	O
+first	O
+inflammatory	O
+process	O
+leading	O
+to	O
+exudates	O
+of	O
+mononuclear	O
+cells	O
+within	O
+alveolar	O
+spaces	O
+,	O
+early	O
+pathologists	O
+observed	O
+an	O
+accumulation	O
+of	O
+lipid	O
+droplets	O
+in	O
+alveolar	O
+macrophages	O
+of	O
+TB	O
+patients	B
+.	O
+
+Tubercle	O
+bacilli	O
+were	O
+shown	O
+to	O
+reside	O
+in	O
+these	O
+lipid	O
+-	O
+rich	O
+macrophages	O
+which	O
+were	O
+named	O
+foamy	O
+macrophages	O
+(	O
+FMs	O
+)	O
+[	O
+30	O
+]	O
+.	O
+
+Recently	O
+,	O
+histo	O
+-	O
+pathological	O
+analysis	O
+of	O
+biopsies	O
+from	O
+patients	B
+with	O
+untreated	O
+tuberculosis	O
+confirmed	O
+the	O
+century	O
+-	O
+old	O
+histological	O
+descriptions	O
+of	O
+postprimary	O
+tuberculosis	O
+[	O
+10	O
+]	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+Hunter	O
+et	O
+al	O
+showed	O
+that	O
+postprimary	O
+tuberculosis	O
+begins	O
+as	O
+a	O
+lipid	O
+pneumonia	O
+with	O
+the	O
+accumulation	O
+of	O
+large	O
+amounts	O
+of	O
+lipid	O
+-	O
+rich	O
+FMs	O
+,	O
+accompanied	O
+by	O
+bronchial	O
+obstruction	O
+.	O
+
+It	O
+was	O
+also	O
+shown	O
+that	O
+in	O
+alveolar	O
+foamy	O
+macrophages	O
+,	O
+the	O
+bacilli	O
+were	O
+mainly	O
+found	O
+within	O
+lipid	O
+droplets	O
+.	O
+
+All	O
+these	O
+observations	O
+underline	O
+the	O
+important	O
+,	O
+yet	O
+often	O
+neglected	O
+,	O
+role	O
+of	O
+lipid	O
+accumulation	O
+,	O
+and	O
+more	O
+precisely	O
+FM	O
+formation	O
+,	O
+at	O
+the	O
+infectious	O
+site	O
+in	O
+the	O
+physiopathology	O
+of	O
+TB	O
+.	O
+
+In	O
+murine	O
+experimental	O
+models	O
+,	O
+FMs	O
+accumulate	O
+within	O
+the	O
+outermost	O
+layer	O
+of	O
+granulomatous	O
+structures	O
+occupying	O
+the	O
+alveolar	O
+spaces	O
+during	O
+the	O
+chronic	O
+phase	O
+of	O
+infection	O
+.	O
+
+This	O
+strongly	O
+suggests	O
+that	O
+FMs	O
+could	O
+be	O
+involved	O
+in	O
+lesion	O
+cleaning	O
+via	O
+phagocytic	O
+uptake	O
+of	O
+cellular	O
+debris	O
+generated	O
+by	O
+the	O
+local	O
+inflammatory	O
+response	O
+.	O
+
+Once	O
+filled	O
+with	O
+debris	O
+,	O
+FMs	O
+would	O
+leave	O
+the	O
+parenchyma	O
+through	O
+the	O
+alveolar	O
+spaces	O
+up	O
+to	O
+the	O
+superior	O
+bronchial	O
+tree	O
+,	O
+to	O
+be	O
+finally	O
+swallowed	O
+and	O
+digested	O
+in	O
+the	O
+stomach	O
+[	O
+31	O
+]	O
+.	O
+
+In	O
+fact	O
+,	O
+this	O
+process	O
+is	O
+very	O
+well	O
+known	O
+,	O
+and	O
+is	O
+a	O
+crucial	O
+factor	O
+for	O
+TB	O
+diagnosis	O
+in	O
+children	B
+.	O
+
+As	O
+infants	B
+do	O
+not	O
+usually	O
+generate	O
+cavitary	O
+lesions	O
+,	O
+and	O
+because	O
+it	O
+is	O
+difficult	O
+to	O
+detect	O
+bacilli	O
+in	O
+the	O
+sputum	O
+,	O
+the	O
+diagnosis	O
+is	O
+linked	O
+to	O
+the	O
+detection	O
+of	O
+bacilli	O
+in	O
+the	O
+gastrointestinal	O
+lavage	O
+[	O
+32	O
+]	O
+.	O
+
+We	O
+show	O
+that	O
+M	B
+.	I
+tb	I
+-	O
+induced	O
+the	O
+transformation	O
+of	O
+in	O
+vitro	O
+-	O
+grown	O
+human	B
+granuloma	O
+macrophages	O
+into	O
+FMs	O
+within	O
+6	O
+days	O
+,	O
+and	O
+even	O
+more	O
+rapidly	O
+(	O
+3	O
+-	O
+4	O
+hours	O
+)	O
+in	O
+cultured	O
+macrophages	O
+.	O
+
+Although	O
+this	O
+event	O
+occurs	O
+more	O
+quickly	O
+than	O
+in	O
+vivo	O
+,	O
+or	O
+in	O
+animal	O
+models	O
+,	O
+our	O
+data	O
+are	O
+consistent	O
+with	O
+the	O
+above	O
+in	O
+vivo	O
+observations	O
+.	O
+
+Within	O
+FMs	O
+,	O
+bacilli	O
+and	O
+LBs	O
+were	O
+often	O
+tightly	O
+linked	O
+,	O
+to	O
+the	O
+point	O
+that	O
+a	O
+non	O
+-	O
+negligible	O
+amount	O
+of	O
+bacteria	O
+were	O
+ultimately	O
+observed	O
+within	O
+LBs	O
+.	O
+
+Interestingly	O
+,	O
+some	O
+of	O
+the	O
+bacilli	O
+transferred	O
+into	O
+lipid	O
+bodies	O
+displayed	O
+their	O
+own	O
+intracytoplasmic	O
+lipid	O
+inclusions	O
+,	O
+which	O
+are	O
+considered	O
+to	O
+be	O
+one	O
+of	O
+the	O
+hallmarks	O
+of	O
+non	O
+-	O
+replicating	O
+(	O
+dormant	O
+)	O
+M	B
+.	I
+tb	I
+[	O
+27	O
+]	O
+.	O
+
+The	O
+recent	O
+observation	O
+of	O
+persistent	O
+ILI	O
+-	O
+containing	O
+tubercle	O
+bacilli	O
+within	O
+adipocyte	O
+LBs	O
+[	O
+33	O
+]	O
+is	O
+in	O
+good	O
+agreement	O
+with	O
+our	O
+observations	O
+.	O
+
+Since	O
+bacilli	O
+residing	O
+in	O
+phagosomes	O
+that	O
+do	O
+not	O
+interact	O
+with	O
+cellular	O
+lipid	O
+bodies	O
+do	O
+not	O
+display	O
+ILIs	O
+,	O
+it	O
+is	O
+tempting	O
+to	O
+assume	O
+that	O
+lipids	O
+within	O
+ILIs	O
+are	O
+of	O
+cellular	O
+origin	O
+.	O
+
+The	O
+accumulation	O
+of	O
+lipids	O
+within	O
+bacilli	O
+[	O
+47	O
+]	O
+,	O
+via	O
+interaction	O
+with	O
+FM	O
+lipid	O
+bodies	O
+could	O
+,	O
+therefore	O
+,	O
+be	O
+crucial	O
+to	O
+M	B
+.	I
+tb	I
+persistence	O
+.	O
+
+It	O
+is	O
+indeed	O
+known	O
+that	O
+M	B
+.	I
+tb	I
+accumulates	O
+lipids	O
+,	O
+and	O
+more	O
+precisely	O
+triacylglycerols	O
+,	O
+during	O
+dormancy	O
+[	O
+34	O
+]	O
+,	O
+[	O
+35	O
+]	O
+from	O
+which	O
+it	O
+derives	O
+both	O
+carbon	O
+and	O
+energy	O
+for	O
+its	O
+own	O
+metabolism	O
+.	O
+
+Intracellular	O
+persistence	O
+of	O
+M	B
+.	I
+tb	I
+is	O
+also	O
+critically	O
+linked	O
+to	O
+the	O
+acquisition	O
+of	O
+host	O
+cholesterol	O
+through	O
+the	O
+Mce4	O
+transporter	O
+system	O
+[	O
+36	O
+]	O
+.	O
+
+The	O
+question	O
+that	O
+arises	O
+is	O
+how	O
+do	O
+bacteria	O
+gain	O
+access	O
+to	O
+lipids	O
+from	O
+LB	O
+?	O
+
+Direct	O
+fusion	O
+of	O
+phagosomes	O
+with	O
+FM	O
+lipid	O
+bodies	O
+seems	O
+unlikely	O
+as	O
+the	O
+membranes	O
+of	O
+both	O
+structures	O
+are	O
+quite	O
+different	O
+from	O
+one	O
+another	O
+.	O
+
+Our	O
+observations	O
+suggest	O
+instead	O
+that	O
+once	O
+M	B
+.	I
+tb	I
+-	O
+containing	O
+phagosomes	O
+have	O
+established	O
+close	O
+contact	O
+with	O
+a	O
+lipid	O
+body	O
+,	O
+they	O
+surround	O
+and	O
+engulf	O
+the	O
+latter	O
+by	O
+a	O
+process	O
+that	O
+remains	O
+to	O
+be	O
+deciphered	O
+.	O
+
+This	O
+phenomenon	O
+is	O
+somewhat	O
+reminiscent	O
+of	O
+autophagy	O
+,	O
+as	O
+observed	O
+under	O
+conditions	O
+of	O
+cholesterol	O
+depletion	O
+in	O
+macrophages	O
+infected	O
+with	O
+M	B
+.	I
+avium	I
+[	O
+37	O
+]	O
+.	O
+
+After	O
+degradation	O
+of	O
+the	O
+resulting	O
+inner	O
+membrane	O
+,	O
+bacteria	O
+would	O
+be	O
+freed	O
+within	O
+the	O
+lipids	O
+of	O
+the	O
+engulfed	O
+LB	O
+,	O
+and	O
+therefore	O
+be	O
+in	O
+direct	O
+contact	O
+with	O
+cellular	O
+lipids	O
+.	O
+
+How	O
+bacilli	O
+translocate	O
+the	O
+cellular	O
+lipids	O
+to	O
+their	O
+own	O
+cytoplasm	O
+remains	O
+to	O
+be	O
+established	O
+.	O
+
+Another	O
+important	O
+phenomenon	O
+underlined	O
+by	O
+our	O
+study	O
+is	O
+the	O
+strong	O
+correlation	O
+between	O
+the	O
+presence	O
+of	O
+FMs	O
+in	O
+the	O
+granulomatous	O
+structures	O
+and	O
+the	O
+development	O
+of	O
+necrosis	O
+within	O
+the	O
+lesion	O
+,	O
+as	O
+suggested	O
+by	O
+Pagel	O
+over	O
+80	O
+years	O
+ago	O
+[	O
+29	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+FMs	O
+were	O
+systematically	O
+located	O
+at	O
+the	O
+interface	O
+region	O
+between	O
+the	O
+histiocytes	O
+and	O
+the	O
+central	O
+necrosis	O
+area	O
+of	O
+the	O
+biopsied	O
+lesions	O
+.	O
+
+Although	O
+necrosis	O
+formation	O
+could	O
+depend	O
+on	O
+an	O
+indirect	O
+effect	O
+of	O
+the	O
+global	O
+immune	O
+response	O
+,	O
+our	O
+data	O
+indicate	O
+that	O
+the	O
+formation	O
+of	O
+FMs	O
+is	O
+an	O
+important	O
+factor	O
+favoring	O
+the	O
+appearance	O
+of	O
+necrosis	O
+.	O
+
+Analysis	O
+of	O
+larger	O
+series	O
+of	O
+biopsy	O
+samples	O
+are	O
+,	O
+however	O
+,	O
+needed	O
+to	O
+definitely	O
+demonstrate	O
+our	O
+actual	O
+hypothesis	O
+according	O
+to	O
+which	O
+FMs	O
+play	O
+a	O
+direct	O
+and	O
+unique	O
+role	O
+in	O
+necrosis	O
+formation	O
+.	O
+
+Consistent	O
+with	O
+this	O
+hypothesis	O
+,	O
+we	O
+observed	O
+that	O
+FMs	O
+induced	O
+from	O
+M	B
+.	I
+tb	I
+-	O
+infected	O
+macrophages	O
+displayed	O
+permanent	O
+TNF	O
+-	O
+alpha	O
+secretion	O
+,	O
+a	O
+potent	O
+pro	O
+-	O
+necrotic	O
+factor	O
+,	O
+whereas	O
+M	B
+.	I
+smegmatis	I
+-	O
+infected	O
+macrophages	O
+were	O
+poor	O
+producers	O
+of	O
+TNF	O
+-	O
+alpha	O
+.	O
+
+At	O
+day	O
+4	O
+post	O
+-	O
+infection	O
+,	O
+TNF	O
+-	O
+alpha	O
+secretion	O
+was	O
+indeed	O
+twofold	O
+higher	O
+in	O
+macrophages	O
+(	O
+of	O
+which	O
+70	O
+%	O
+had	O
+differentiated	O
+into	O
+FMs	O
+)	O
+infected	O
+with	O
+M	B
+.	I
+tb	I
+than	O
+in	O
+those	O
+infected	O
+with	O
+M	B
+.	I
+smegmatis	I
+,	O
+as	O
+measured	O
+both	O
+by	O
+ELISA	O
+and	O
+RNA	O
+quantification	O
+(	O
+Peyron	O
+,	O
+unpublished	O
+observations	O
+)	O
+.	O
+
+However	O
+,	O
+one	O
+must	O
+keep	O
+in	O
+mind	O
+that	O
+the	O
+association	O
+of	O
+FMs	O
+and	O
+necrosis	O
+may	O
+be	O
+the	O
+consequence	O
+of	O
+the	O
+FM	O
+cleaning	O
+process	O
+of	O
+lipoproteins	O
+released	O
+into	O
+the	O
+necrotic	O
+tissue	O
+,	O
+as	O
+observed	O
+in	O
+atherosclerosis	O
+lesions	O
+[	O
+38	O
+]	O
+.	O
+
+It	O
+is	O
+thus	O
+tempting	O
+to	O
+propose	O
+that	O
+M	B
+.	I
+tb	I
+mycolic	O
+acids	O
+may	O
+be	O
+responsible	O
+for	O
+the	O
+development	O
+of	O
+necrotic	O
+lesions	O
+,	O
+due	O
+to	O
+their	O
+ability	O
+to	O
+induce	O
+TNF	O
+-	O
+alpha	O
+production	O
+by	O
+FMs	O
+.	O
+
+Whether	O
+mycolic	O
+acids	O
+are	O
+directly	O
+involved	O
+in	O
+TNF	O
+-	O
+alpha	O
+production	O
+,	O
+or	O
+only	O
+indirectly	O
+by	O
+inducing	O
+FM	O
+formation	O
+,	O
+remains	O
+a	O
+matter	O
+of	O
+debate	O
+currently	O
+under	O
+study	O
+.	O
+
+Our	O
+observations	O
+are	O
+strikingly	O
+similar	O
+to	O
+the	O
+phenomena	O
+described	O
+for	O
+postprimary	O
+tuberculosis	O
+,	O
+that	O
+seems	O
+to	O
+begin	O
+as	O
+localized	O
+foci	O
+of	O
+pneumonia	O
+followed	O
+by	O
+massive	O
+necrosis	O
+leading	O
+to	O
+the	O
+formation	O
+of	O
+pulmonary	O
+cavities	O
+[	O
+10	O
+]	O
+.	O
+
+If	O
+this	O
+proves	O
+to	O
+be	O
+the	O
+case	O
+,	O
+then	O
+the	O
+traditionally	O
+admitted	O
+phenomenon	O
+of	O
+cavitation	O
+arising	O
+from	O
+the	O
+erosion	O
+of	O
+caseating	O
+granulomatous	O
+structures	O
+from	O
+bronchi	O
+can	O
+be	O
+ruled	O
+out	O
+[	O
+39	O
+]	O
+.	O
+
+In	O
+our	O
+study	O
+,	O
+we	O
+successfully	O
+induced	O
+FM	O
+formation	O
+from	O
+isolated	O
+macrophages	O
+infected	O
+with	O
+M	B
+.	I
+tb	I
+,	O
+i	O
+.	O
+e	O
+.	O
+outside	O
+a	O
+granulomatous	O
+structure	O
+,	O
+which	O
+is	O
+consistent	O
+with	O
+Hunter	O
+'	O
+s	O
+recent	O
+proposal	O
+.	O
+
+Until	O
+now	O
+,	O
+mycolic	O
+acids	O
+have	O
+been	O
+considered	O
+to	O
+be	O
+indirectly	O
+involved	O
+in	O
+virulence	O
+mechanisms	O
+as	O
+being	O
+part	O
+of	O
+complex	O
+molecules	O
+of	O
+the	O
+mycobacterial	O
+envelope	O
+.	O
+
+The	O
+most	O
+widely	O
+studied	O
+mycolic	O
+acid	O
+-	O
+containing	O
+mycobacterial	O
+compound	O
+trehalose	O
+6	O
+,	O
+6	O
+'	O
+dimycolate	O
+(	O
+TDM	O
+)	O
+,	O
+has	O
+been	O
+extensively	O
+analyzed	O
+for	O
+its	O
+role	O
+in	O
+virulence	O
+since	O
+the	O
+mid	O
+-	O
+fifties	O
+[	O
+40	O
+]	O
+.	O
+
+Recently	O
+,	O
+it	O
+was	O
+shown	O
+to	O
+interfere	O
+with	O
+the	O
+host	O
+granulomatous	O
+response	O
+[	O
+41	O
+]	O
+.	O
+
+Overall	O
+,	O
+TDM	O
+was	O
+mainly	O
+shown	O
+to	O
+mediate	O
+macrophage	O
+activation	O
+and	O
+a	O
+Th1	O
+-	O
+type	O
+response	O
+to	O
+M	B
+.	I
+tb	I
+infection	O
+(	O
+for	O
+review	O
+,	O
+see	O
+[	O
+25	O
+]	O
+)	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+a	O
+direct	O
+role	O
+of	O
+oxygenated	O
+mycolic	O
+acids	O
+for	O
+FM	O
+formation	O
+,	O
+independently	O
+from	O
+the	O
+appearance	O
+and	O
+stage	O
+of	O
+the	O
+disease	O
+.	O
+
+M	B
+.	I
+tb	I
+-	O
+specific	O
+mycolic	O
+acids	O
+indeed	O
+trigger	O
+the	O
+transformation	O
+of	O
+both	O
+isolated	O
+and	O
+granuloma	O
+macrophages	O
+,	O
+into	O
+FM	O
+.	O
+
+Given	O
+the	O
+absence	O
+of	O
+FM	O
+formation	O
+in	O
+M	B
+.	I
+smegmatis	I
+-	O
+induced	O
+granulomas	O
+,	O
+despite	O
+the	O
+induction	O
+of	O
+a	O
+comparative	O
+inflammatory	O
+response	O
+,	O
+ascertained	O
+by	O
+the	O
+similar	O
+induction	O
+of	O
+granulomas	O
+,	O
+this	O
+phenomenon	O
+clearly	O
+depends	O
+upon	O
+a	O
+direct	O
+contact	O
+with	O
+the	O
+bacilli	O
+,	O
+and	O
+not	O
+to	O
+the	O
+inflammatory	O
+response	O
+.	O
+
+Mycolic	O
+acids	O
+are	O
+major	O
+and	O
+hallmark	O
+components	O
+of	O
+the	O
+mycobacterial	O
+cell	O
+wall	O
+.	O
+
+They	O
+constitute	O
+40	O
+-	O
+60	O
+%	O
+of	O
+dry	O
+weight	O
+of	O
+the	O
+envelope	O
+[	O
+42	O
+]	O
+.	O
+
+All	O
+members	O
+of	O
+the	O
+complex	O
+(	O
+e	O
+.	O
+g	O
+.	O
+M	B
+.	I
+tb	I
+,	O
+Mycobacterium	B
+africanum	I
+,	O
+Mycobacterium	B
+bovis	I
+and	O
+Mycobacterium	B
+microti	I
+)	O
+are	O
+able	O
+to	O
+synthesize	O
+the	O
+same	O
+combination	O
+of	O
+mycolic	O
+acids	O
+,	O
+i	O
+.	O
+e	O
+.	O
+cyclopropanated	O
+alpha	O
+-	O
+mycolic	O
+acids	O
+,	O
+ketomycolic	O
+and	O
+methoxymycolic	O
+acids	O
+[	O
+17	O
+]	O
+,	O
+which	O
+are	O
+not	O
+synthesized	O
+by	O
+non	O
+-	O
+pathogenic	O
+mycobacterial	O
+species	O
+[	O
+43	O
+]	O
+.	O
+
+These	O
+structural	O
+specificities	O
+probably	O
+account	O
+for	O
+part	O
+of	O
+the	O
+pathogenicity	O
+of	O
+these	O
+species	O
+,	O
+as	O
+shown	O
+by	O
+the	O
+impaired	O
+virulence	O
+of	O
+mutant	O
+strains	O
+deprived	O
+of	O
+keto	O
+and	O
+methoxyl	O
+groups	O
+in	O
+experimental	O
+infections	O
+[	O
+17	O
+]	O
+,	O
+[	O
+44	O
+]	O
+,	O
+[	O
+45	O
+]	O
+.	O
+
+Our	O
+study	O
+,	O
+therefore	O
+,	O
+gives	O
+the	O
+first	O
+proof	O
+of	O
+a	O
+direct	O
+role	O
+of	O
+isolated	O
+mycolic	O
+acids	O
+in	O
+the	O
+interplay	O
+between	O
+M	B
+.	I
+tb	I
+and	O
+host	O
+cells	O
+.	O
+
+Interestingly	O
+,	O
+this	O
+effect	O
+is	O
+expressed	O
+both	O
+by	O
+whole	O
+bacilli	O
+and	O
+isolated	O
+lipids	O
+,	O
+suggesting	O
+that	O
+oxygenated	O
+mycolic	O
+acids	O
+are	O
+either	O
+secreted	O
+by	O
+the	O
+bacilli	O
+,	O
+or	O
+exposed	O
+at	O
+the	O
+cell	O
+wall	O
+surface	O
+in	O
+a	O
+manner	O
+enabling	O
+their	O
+bioactivity	O
+.	O
+
+According	O
+to	O
+our	O
+results	O
+,	O
+mycolic	O
+acids	O
+trigger	O
+the	O
+formation	O
+,	O
+within	O
+granulomas	O
+,	O
+of	O
+FMs	O
+in	O
+which	O
+bacilli	O
+can	O
+hide	O
+and	O
+survive	O
+.	O
+
+Oxygenated	O
+mycolic	O
+acids	O
+,	O
+either	O
+free	O
+,	O
+as	O
+constituents	O
+of	O
+TDM	O
+[	O
+44	O
+]	O
+,	O
+or	O
+linked	O
+to	O
+the	O
+cell	O
+wall	O
+arabinogalactan	O
+[	O
+46	O
+]	O
+,	O
+[	O
+47	O
+]	O
+,	O
+should	O
+,	O
+therefore	O
+,	O
+be	O
+considered	O
+as	O
+major	O
+virulence	O
+factors	O
+enabling	O
+M	B
+.	I
+tb	I
+survival	O
+for	O
+long	O
+periods	O
+of	O
+time	O
+in	O
+a	O
+persistent	O
+state	O
+.	O
+
+Being	O
+an	O
+inducer	O
+of	O
+host	O
+lipid	O
+accumulation	O
+,	O
+and	O
+FM	O
+formation	O
+at	O
+the	O
+site	O
+of	O
+infection	O
+,	O
+these	O
+oxygenated	O
+mycolic	O
+acids	O
+could	O
+,	O
+therefore	O
+,	O
+also	O
+be	O
+responsible	O
+for	O
+the	O
+induction	O
+of	O
+necrosis	O
+within	O
+lesions	O
+,	O
+thus	O
+favoring	O
+M	B
+.	I
+tb	I
+dissemination	O
+.	O
+
+Interestingly	O
+,	O
+deletion	O
+of	O
+the	O
+mmaA4	O
+(	O
+Rv0642c	O
+)	O
+gene	O
+also	O
+drastically	O
+decreased	O
+the	O
+ability	O
+of	O
+M	B
+.	I
+tb	I
+to	O
+induce	O
+the	O
+differentiation	O
+of	O
+macrophages	O
+into	O
+FMs	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+residual	O
+ability	O
+of	O
+this	O
+mutant	O
+to	O
+induce	O
+FMs	O
+suggests	O
+that	O
+other	O
+mycobacterial	O
+factors	O
+might	O
+partially	O
+trigger	O
+the	O
+formation	O
+of	O
+FM	O
+.	O
+
+With	O
+regard	O
+to	O
+the	O
+mycolic	O
+acid	O
+methyltransferases	O
+,	O
+given	O
+that	O
+(	O
+i	O
+)	O
+mmaA2	O
+(	O
+Rv0644c	O
+)	O
+and	O
+mmaA3	O
+(	O
+Rv0643c	O
+)	O
+are	O
+pseudogenes	O
+in	O
+M	B
+.	I
+leprae	I
+and	O
+(	O
+ii	O
+)	O
+mmaA4	O
+KO	O
+present	O
+no	O
+trans	O
+cyclopropanation	O
+[	O
+45	O
+]	O
+,	O
+thus	O
+excluding	O
+the	O
+involvement	O
+of	O
+the	O
+cmaA2	O
+(	O
+Rv0503c	O
+)	O
+gene	O
+,	O
+we	O
+expect	O
+that	O
+at	O
+least	O
+pcaA	O
+(	O
+Rv0470c	O
+)	O
+,	O
+which	O
+introduces	O
+cis	O
+-	O
+cyclopropane	O
+,	O
+may	O
+play	O
+the	O
+same	O
+role	O
+.	O
+
+Consistent	O
+with	O
+this	O
+hypothesis	O
+,	O
+a	O
+pcaA	O
+null	O
+mutant	O
+is	O
+unable	O
+to	O
+persist	O
+within	O
+infected	O
+mice	B
+[	O
+46	O
+]	O
+,	O
+thus	O
+demonstrating	O
+the	O
+role	O
+of	O
+a	O
+mycolic	O
+acid	O
+methyltransferase	O
+in	O
+the	O
+chronic	O
+stage	O
+of	O
+infection	O
+.	O
+
+Overall	O
+,	O
+our	O
+study	O
+has	O
+shed	O
+light	O
+on	O
+a	O
+previously	O
+uncharacterized	O
+cell	O
+population	O
+participating	O
+in	O
+human	B
+tuberculous	O
+granulomas	O
+,	O
+namely	O
+foamy	O
+macrophages	O
+.	O
+
+We	O
+propose	O
+that	O
+the	O
+specific	O
+induction	O
+of	O
+FM	O
+by	O
+M	B
+.	I
+tb	I
+would	O
+create	O
+a	O
+favourable	O
+environment	O
+for	O
+persistent	O
+bacteria	O
+.	O
+
+In	O
+our	O
+opinion	O
+,	O
+FMs	O
+could	O
+be	O
+a	O
+safe	O
+shelter	O
+because	O
+they	O
+preserve	O
+bacilli	O
+from	O
+a	O
+direct	O
+contact	O
+with	O
+granuloma	O
+lymphocytes	O
+and	O
+histiocytes	O
+,	O
+they	O
+lose	O
+one	O
+of	O
+the	O
+major	O
+macrophage	O
+bactericidal	O
+activities	O
+and	O
+they	O
+constitute	O
+an	O
+important	O
+source	O
+of	O
+nutrients	O
+for	O
+the	O
+bacilli	O
+thanks	O
+to	O
+the	O
+fatty	O
+acids	O
+accumulated	O
+in	O
+their	O
+lipid	O
+granules	O
+.	O
+
+Supporting	O
+Information	O
+
+A	O
+Case	O
+-	O
+Control	O
+Study	O
+to	O
+Assess	O
+the	O
+Relationship	O
+between	O
+Poverty	O
+and	O
+Visual	O
+Impairment	O
+from	O
+Cataract	O
+in	O
+Kenya	O
+,	O
+the	O
+Philippines	O
+,	O
+and	O
+Bangladesh	O
+
+Abstract	O
+
+Background	O
+
+The	O
+link	O
+between	O
+poverty	O
+and	O
+health	O
+is	O
+central	O
+to	O
+the	O
+Millennium	O
+Development	O
+Goals	O
+(	O
+MDGs	O
+)	O
+.	O
+
+Poverty	O
+can	O
+be	O
+both	O
+a	O
+cause	O
+and	O
+consequence	O
+of	O
+poor	O
+health	O
+,	O
+but	O
+there	O
+are	O
+few	O
+epidemiological	O
+studies	O
+exploring	O
+this	O
+complex	O
+relationship	O
+.	O
+
+The	O
+aim	O
+of	O
+this	O
+study	O
+was	O
+to	O
+examine	O
+the	O
+association	O
+between	O
+visual	O
+impairment	O
+from	O
+cataract	O
+and	O
+poverty	O
+in	O
+adults	O
+in	O
+Kenya	O
+,	O
+Bangladesh	O
+,	O
+and	O
+the	O
+Philippines	O
+.	O
+
+Methods	O
+and	O
+Findings	O
+
+A	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+was	O
+conducted	O
+in	O
+three	O
+countries	O
+during	O
+2005	O
+-	O
+2006	O
+.	O
+
+Cases	O
+were	O
+persons	B
+aged	O
+50	O
+y	O
+or	O
+older	O
+and	O
+visually	O
+impaired	O
+due	O
+to	O
+cataract	O
+(	O
+visual	O
+acuity	O
+<	O
+6	O
+/	O
+24	O
+in	O
+the	O
+better	O
+eye	O
+)	O
+.	O
+
+Controls	O
+were	O
+persons	B
+age	O
+-	O
+and	O
+sex	O
+-	O
+matched	O
+to	O
+the	O
+case	O
+participants	B
+with	O
+normal	O
+vision	O
+selected	O
+from	O
+the	O
+same	O
+cluster	O
+.	O
+
+Household	O
+expenditure	O
+was	O
+assessed	O
+through	O
+the	O
+collection	O
+of	O
+detailed	O
+consumption	O
+data	O
+,	O
+and	O
+asset	O
+ownership	O
+and	O
+self	O
+-	O
+rated	O
+wealth	O
+were	O
+also	O
+measured	O
+.	O
+
+In	O
+total	O
+,	O
+596	O
+cases	O
+and	O
+535	O
+controls	O
+were	O
+included	O
+in	O
+these	O
+analyses	O
+(	O
+Kenya	O
+142	O
+cases	O
+,	O
+75	O
+controls	O
+;	O
+Bangladesh	O
+216	O
+cases	O
+,	O
+279	O
+controls	O
+;	O
+Philippines	O
+238	O
+cases	O
+,	O
+180	O
+controls	O
+)	O
+.	O
+
+Case	O
+participants	B
+were	O
+more	O
+likely	O
+to	O
+be	O
+in	O
+the	O
+lowest	O
+quartile	O
+of	O
+per	O
+capita	O
+expenditure	O
+(	O
+PCE	O
+)	O
+compared	O
+to	O
+controls	O
+in	O
+Kenya	O
+(	O
+odds	O
+ratio	O
+=	O
+2	O
+.	O
+3	O
+,	O
+95	O
+%	O
+confidence	O
+interval	O
+0	O
+.	O
+9	O
+-	O
+5	O
+.	O
+5	O
+)	O
+,	O
+Bangladesh	O
+(	O
+1	O
+.	O
+9	O
+,	O
+1	O
+.	O
+1	O
+-	O
+3	O
+.	O
+2	O
+)	O
+,	O
+and	O
+the	O
+Philippines	O
+(	O
+3	O
+.	O
+1	O
+,	O
+1	O
+.	O
+7	O
+-	O
+5	O
+.	O
+7	O
+)	O
+,	O
+and	O
+there	O
+was	O
+significant	O
+dose	O
+-	O
+response	O
+relationship	O
+across	O
+quartiles	O
+of	O
+PCE	O
+.	O
+
+These	O
+associations	O
+persisted	O
+after	O
+adjustment	O
+for	O
+self	O
+-	O
+rated	O
+health	O
+and	O
+social	O
+support	O
+indicators	O
+.	O
+
+A	O
+similar	O
+pattern	O
+was	O
+observed	O
+for	O
+the	O
+relationship	O
+between	O
+cataract	O
+visual	O
+impairment	O
+with	O
+asset	O
+ownership	O
+and	O
+self	O
+-	O
+rated	O
+wealth	O
+.	O
+
+There	O
+was	O
+no	O
+consistent	O
+pattern	O
+of	O
+association	O
+between	O
+PCE	O
+and	O
+level	O
+of	O
+visual	O
+impairment	O
+due	O
+to	O
+cataract	O
+,	O
+sex	O
+,	O
+or	O
+age	O
+among	O
+the	O
+three	O
+countries	O
+.	O
+
+Conclusions	O
+
+Our	O
+data	O
+show	O
+that	O
+people	B
+with	O
+visual	O
+impairment	O
+due	O
+to	O
+cataract	O
+were	O
+poorer	O
+than	O
+those	O
+with	O
+normal	O
+sight	O
+in	O
+all	O
+three	O
+low	O
+-	O
+income	O
+countries	O
+studied	O
+.	O
+
+The	O
+MDGs	O
+are	O
+committed	O
+to	O
+the	O
+eradication	O
+of	O
+extreme	O
+poverty	O
+and	O
+provision	O
+of	O
+health	O
+care	O
+to	O
+poor	O
+people	B
+,	O
+and	O
+this	O
+study	O
+highlights	O
+the	O
+need	O
+for	O
+increased	O
+provision	O
+of	O
+cataract	O
+surgery	O
+to	O
+poor	O
+people	B
+,	O
+as	O
+they	O
+are	O
+particularly	O
+vulnerable	O
+to	O
+visual	O
+impairment	O
+from	O
+cataract	O
+.	O
+
+Background	O
+.	O
+
+Globally	O
+,	O
+about	O
+45	O
+million	O
+people	B
+are	O
+blind	O
+.	O
+
+As	O
+with	O
+many	O
+other	O
+conditions	O
+,	O
+avoidable	O
+blindness	O
+(	O
+preventable	O
+or	O
+curable	O
+blindness	O
+)	O
+is	O
+a	O
+particular	O
+problem	O
+for	O
+people	B
+in	O
+developing	O
+countries	O
+-	O
+-	O
+90	O
+%	O
+of	O
+blind	O
+people	B
+live	O
+in	O
+poor	O
+regions	O
+of	O
+the	O
+world	O
+.	O
+
+Although	O
+various	O
+infections	O
+and	O
+disorders	O
+can	O
+cause	O
+blindness	O
+,	O
+cataract	O
+is	O
+the	O
+most	O
+common	O
+cause	O
+.	O
+
+In	O
+cataract	O
+,	O
+which	O
+is	O
+responsible	O
+for	O
+half	O
+of	O
+all	O
+cases	O
+of	O
+blindness	O
+in	O
+the	O
+world	O
+,	O
+the	O
+lens	O
+of	O
+the	O
+eye	O
+gradually	O
+becomes	O
+cloudy	O
+.	O
+
+Because	O
+the	O
+lens	O
+focuses	O
+light	O
+to	O
+produce	O
+clear	O
+,	O
+sharp	O
+images	O
+,	O
+as	O
+cataract	O
+develops	O
+,	O
+vision	O
+becomes	O
+increasingly	O
+foggy	O
+or	O
+fuzzy	O
+,	O
+colors	O
+become	O
+less	O
+intense	O
+,	O
+and	O
+the	O
+ability	O
+to	O
+see	O
+shapes	O
+against	O
+a	O
+background	O
+declines	O
+.	O
+
+Eventually	O
+,	O
+vision	O
+may	O
+be	O
+lost	O
+completely	O
+.	O
+
+Cataract	O
+can	O
+be	O
+treated	O
+with	O
+an	O
+inexpensive	O
+,	O
+simple	O
+operation	O
+in	O
+which	O
+the	O
+cloudy	O
+lens	O
+is	O
+surgically	O
+removed	O
+and	O
+an	O
+artificial	O
+lens	O
+is	O
+inserted	O
+into	O
+the	O
+eye	O
+to	O
+restore	O
+vision	O
+.	O
+
+In	O
+developed	O
+countries	O
+,	O
+this	O
+operation	O
+is	O
+common	O
+and	O
+easily	O
+accessible	O
+but	O
+many	O
+poor	O
+countries	O
+lack	O
+the	O
+resources	O
+to	O
+provide	O
+the	O
+operation	O
+to	O
+everyone	O
+who	O
+needs	O
+it	O
+.	O
+
+In	O
+addition	O
+,	O
+blind	O
+people	B
+often	O
+cannot	O
+afford	O
+to	O
+travel	O
+to	O
+the	O
+hospitals	O
+where	O
+the	O
+operation	O
+,	O
+which	O
+also	O
+may	O
+come	O
+with	O
+a	O
+fee	O
+,	O
+is	O
+done	O
+.	O
+
+Why	O
+Was	O
+This	O
+Study	O
+Done	O
+?	O
+
+Because	O
+blindness	O
+may	O
+reduce	O
+earning	O
+potential	O
+,	O
+many	O
+experts	O
+believe	O
+that	O
+poverty	O
+and	O
+blindness	O
+(	O
+and	O
+,	O
+more	O
+generally	O
+,	O
+poor	O
+health	O
+)	O
+are	O
+inextricably	O
+linked	O
+.	O
+
+People	B
+become	O
+ill	O
+more	O
+often	O
+in	O
+poor	O
+countries	O
+than	O
+in	O
+wealthy	O
+countries	O
+because	O
+they	O
+have	O
+insufficient	O
+food	O
+,	O
+live	O
+in	O
+substandard	O
+housing	O
+,	O
+and	O
+have	O
+limited	O
+access	O
+to	O
+health	O
+care	O
+,	O
+education	O
+,	O
+water	O
+,	O
+and	O
+sanitation	O
+.	O
+
+Once	O
+they	O
+are	O
+ill	O
+,	O
+their	O
+ability	O
+to	O
+earn	O
+money	O
+may	O
+be	O
+reduced	O
+,	O
+which	O
+increases	O
+their	O
+personal	O
+poverty	O
+and	O
+slows	O
+the	O
+economic	O
+development	O
+of	O
+the	O
+whole	O
+country	O
+.	O
+
+Because	O
+of	O
+this	O
+potential	O
+link	O
+between	O
+health	O
+and	O
+poverty	O
+,	O
+improvements	O
+in	O
+health	O
+are	O
+at	O
+the	O
+heart	O
+of	O
+the	O
+United	O
+Nations	O
+Millennium	O
+Development	O
+Goals	O
+,	O
+a	O
+set	O
+of	O
+eight	O
+goals	O
+established	O
+in	O
+2000	O
+with	O
+the	O
+primary	O
+aim	O
+of	O
+reducing	O
+world	O
+poverty	O
+.	O
+
+However	O
+,	O
+few	O
+studies	O
+have	O
+actually	O
+investigated	O
+the	O
+complex	O
+relationship	O
+between	O
+poverty	O
+and	O
+health	O
+.	O
+
+Here	O
+,	O
+the	O
+researchers	O
+investigate	O
+the	O
+association	O
+between	O
+visual	O
+impairment	O
+from	O
+cataract	O
+and	O
+poverty	O
+among	O
+adults	O
+living	O
+in	O
+three	O
+low	O
+-	O
+income	O
+countries	O
+.	O
+
+What	O
+Did	O
+the	O
+Researchers	O
+Do	O
+and	O
+Find	O
+?	O
+
+The	O
+researchers	O
+identified	O
+nearly	O
+600	O
+people	B
+aged	O
+50	O
+y	O
+or	O
+more	O
+with	O
+severe	O
+cataract	O
+-	O
+induced	O
+visual	O
+impairment	O
+(	O
+"	O
+cases	O
+"	O
+)	O
+primarily	O
+through	O
+a	O
+survey	O
+of	O
+the	O
+population	O
+in	O
+Kenya	O
+,	O
+Bangladesh	O
+,	O
+and	O
+the	O
+Philippines	O
+.	O
+
+They	O
+matched	O
+each	O
+case	O
+to	O
+a	O
+normally	O
+sighted	O
+(	O
+"	O
+control	O
+"	O
+)	O
+person	B
+of	O
+similar	O
+age	O
+and	O
+sex	O
+living	O
+nearby	O
+.	O
+
+They	O
+then	O
+assessed	O
+a	O
+proxy	O
+for	O
+the	O
+income	O
+level	O
+,	O
+measured	O
+as	O
+"	O
+per	O
+capita	O
+expenditure	O
+"	O
+(	O
+PCE	O
+)	O
+,	O
+of	O
+all	O
+the	O
+study	O
+participants	B
+(	O
+people	B
+with	O
+cataracts	O
+and	O
+controls	O
+)	O
+by	O
+collecting	O
+information	O
+about	O
+what	O
+their	O
+households	O
+consumed	O
+.	O
+
+The	O
+participants	B
+'	O
+housing	O
+conditions	O
+and	O
+other	O
+assets	O
+and	O
+their	O
+self	O
+-	O
+rated	O
+wealth	O
+were	O
+also	O
+measured	O
+.	O
+
+In	O
+all	O
+three	O
+countries	O
+,	O
+cases	O
+were	O
+more	O
+likely	O
+to	O
+be	O
+in	O
+the	O
+lowest	O
+quarter	O
+(	O
+quartile	O
+)	O
+of	O
+the	O
+range	O
+of	O
+PCEs	O
+for	O
+that	O
+country	O
+than	O
+controls	O
+.	O
+
+In	O
+the	O
+Philippines	O
+,	O
+for	O
+example	O
+,	O
+people	B
+with	O
+cataract	O
+-	O
+affected	O
+vision	O
+were	O
+three	O
+times	O
+more	O
+likely	O
+than	O
+normally	O
+sighted	O
+controls	O
+to	O
+have	O
+a	O
+PCE	O
+in	O
+the	O
+lowest	O
+quartile	O
+than	O
+in	O
+the	O
+highest	O
+quartile	O
+.	O
+
+The	O
+risk	O
+of	O
+cataract	O
+-	O
+related	O
+visual	O
+impairment	O
+increased	O
+as	O
+PCE	O
+decreased	O
+in	O
+all	O
+three	O
+countries	O
+.	O
+
+Similarly	O
+,	O
+severe	O
+cataract	O
+-	O
+induced	O
+visual	O
+impairment	O
+was	O
+more	O
+common	O
+in	O
+those	O
+who	O
+owned	O
+fewer	O
+assets	O
+and	O
+those	O
+with	O
+lower	O
+self	O
+-	O
+rated	O
+wealth	O
+.	O
+
+However	O
+,	O
+there	O
+was	O
+no	O
+consistent	O
+association	O
+between	O
+PCE	O
+and	O
+the	O
+level	O
+of	O
+cataract	O
+-	O
+induced	O
+visual	O
+impairment	O
+.	O
+
+What	O
+Do	O
+These	O
+Findings	O
+Mean	O
+?	O
+
+These	O
+findings	O
+show	O
+that	O
+there	O
+is	O
+an	O
+association	O
+between	O
+visual	O
+impairment	O
+caused	O
+by	O
+cataract	O
+and	O
+poverty	O
+in	O
+Kenya	O
+,	O
+Bangladesh	O
+,	O
+and	O
+the	O
+Philippines	O
+.	O
+
+However	O
+,	O
+because	O
+the	O
+financial	O
+circumstances	O
+of	O
+the	O
+people	B
+in	O
+this	O
+study	O
+were	O
+assessed	O
+after	O
+cataracts	O
+had	O
+impaired	O
+their	O
+sight	O
+,	O
+this	O
+study	O
+does	O
+not	O
+prove	O
+that	O
+poverty	O
+is	O
+a	O
+cause	O
+of	O
+visual	O
+impairment	O
+.	O
+
+A	O
+causal	O
+connection	O
+between	O
+poverty	O
+and	O
+cataract	O
+can	O
+only	O
+be	O
+shown	O
+by	O
+determining	O
+the	O
+PCEs	O
+of	O
+normally	O
+sighted	O
+people	B
+and	O
+following	O
+them	O
+for	O
+several	O
+years	O
+to	O
+see	O
+who	O
+develops	O
+cataract	O
+.	O
+
+Nevertheless	O
+,	O
+by	O
+confirming	O
+an	O
+association	O
+between	O
+poverty	O
+and	O
+blindness	O
+,	O
+these	O
+findings	O
+highlight	O
+the	O
+need	O
+for	O
+increased	O
+provision	O
+of	O
+cataract	O
+surgery	O
+to	O
+poor	O
+people	B
+,	O
+particularly	O
+since	O
+cataract	O
+surgery	O
+has	O
+the	O
+potential	O
+to	O
+improve	O
+the	O
+quality	O
+of	O
+life	O
+for	O
+many	O
+people	B
+in	O
+developing	O
+countries	O
+at	O
+a	O
+relatively	O
+low	O
+cost	O
+.	O
+
+Additional	O
+Information	O
+.	O
+
+Please	O
+access	O
+these	O
+Web	O
+sites	O
+via	O
+the	O
+online	O
+version	O
+of	O
+this	O
+summary	O
+at	O
+http	O
+:	O
+/	O
+/	O
+dx	O
+.	O
+doi	O
+.	O
+org	O
+/	O
+10	O
+.	O
+1371	O
+/	O
+journal	O
+.	O
+pmed	O
+.	O
+0050244	O
+.	O
+
+Introduction	O
+
+Improvements	O
+in	O
+health	O
+are	O
+at	O
+the	O
+heart	O
+of	O
+the	O
+Millennium	O
+Development	O
+Goals	O
+,	O
+with	O
+the	O
+recognition	O
+that	O
+better	O
+health	O
+is	O
+central	O
+to	O
+the	O
+primary	O
+aim	O
+of	O
+reducing	O
+poverty	O
+as	O
+well	O
+as	O
+important	O
+in	O
+its	O
+own	O
+right	O
+.	O
+
+Empirical	O
+data	O
+are	O
+needed	O
+to	O
+back	O
+up	O
+this	O
+claim	O
+.	O
+
+Unravelling	O
+the	O
+relationship	O
+between	O
+blindness	O
+and	O
+poverty	O
+therefore	O
+has	O
+important	O
+implications	O
+,	O
+and	O
+may	O
+also	O
+be	O
+informative	O
+for	O
+the	O
+association	O
+between	O
+poverty	O
+and	O
+other	O
+disabilities	O
+.	O
+
+Blindness	O
+is	O
+a	O
+common	O
+condition	O
+globally	O
+,	O
+affecting	O
+approximately	O
+45	O
+million	O
+people	B
+,	O
+and	O
+more	O
+than	O
+a	O
+third	O
+of	O
+blindness	O
+is	O
+caused	O
+by	O
+cataract	O
+[	O
+1	O
+,	O
+2	O
+]	O
+.	O
+
+Globally	O
+,	O
+the	O
+prevalence	O
+of	O
+blindness	O
+is	O
+five	O
+-	O
+fold	O
+higher	O
+in	O
+poor	O
+than	O
+rich	O
+countries	O
+[	O
+2	O
+]	O
+.	O
+
+Limited	O
+data	O
+show	O
+that	O
+within	O
+countries	O
+the	O
+poor	O
+are	O
+also	O
+more	O
+likely	O
+to	O
+be	O
+blind	O
+[	O
+3	O
+,	O
+4	O
+]	O
+.	O
+
+It	O
+is	O
+frequently	O
+asserted	O
+that	O
+blindness	O
+is	O
+both	O
+a	O
+cause	O
+and	O
+consequence	O
+of	O
+poverty	O
+,	O
+but	O
+there	O
+are	O
+few	O
+empirical	O
+data	O
+to	O
+support	O
+this	O
+claim	O
+.	O
+
+Poverty	O
+may	O
+cause	O
+cataract	O
+blindness	O
+,	O
+because	O
+access	O
+to	O
+cataract	O
+surgery	O
+is	O
+limited	O
+in	O
+low	O
+-	O
+income	O
+countries	O
+[	O
+5	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+within	O
+poor	O
+countries	O
+some	O
+evidence	O
+suggests	O
+that	O
+lack	O
+of	O
+money	O
+is	O
+a	O
+major	O
+barrier	O
+to	O
+uptake	O
+of	O
+cataract	O
+surgery	O
+by	O
+individuals	O
+[	O
+6	O
+-	O
+8	O
+]	O
+.	O
+
+Blindness	O
+may	O
+also	O
+cause	O
+poverty	O
+,	O
+as	O
+the	O
+blind	O
+individual	O
+,	O
+or	O
+the	O
+household	O
+members	O
+who	O
+care	O
+for	O
+them	O
+,	O
+have	O
+a	O
+reduced	O
+earning	O
+potential	O
+[	O
+4	O
+,	O
+9	O
+]	O
+.	O
+
+This	O
+complex	O
+problem	O
+could	O
+have	O
+serious	O
+implications	O
+;	O
+estimates	O
+from	O
+The	O
+Gambia	O
+suggest	O
+that	O
+there	O
+is	O
+a	O
+substantial	O
+economic	O
+burden	O
+from	O
+lost	O
+productivity	O
+among	O
+blind	O
+people	B
+[	O
+10	O
+]	O
+.	O
+
+Therefore	O
+,	O
+blindness	O
+prevention	O
+may	O
+ultimately	O
+be	O
+cost	O
+saving	O
+[	O
+11	O
+]	O
+.	O
+
+Extrapolations	O
+on	O
+a	O
+global	O
+level	O
+indicate	O
+that	O
+a	O
+successful	O
+eye	O
+care	O
+programme	O
+could	O
+prevent	O
+more	O
+than	O
+100	O
+million	O
+cases	O
+of	O
+blindness	O
+between	O
+2000	O
+and	O
+2020	O
+,	O
+and	O
+consequently	O
+save	O
+at	O
+least	O
+US	O
+$	O
+102	O
+billion	O
+,	O
+which	O
+would	O
+otherwise	O
+be	O
+lost	O
+to	O
+reductions	O
+in	O
+productivity	O
+associated	O
+with	O
+blindness	O
+[	O
+12	O
+]	O
+.	O
+
+However	O
+,	O
+these	O
+estimates	O
+are	O
+based	O
+on	O
+extrapolations	O
+from	O
+limited	O
+data	O
+and	O
+were	O
+not	O
+based	O
+on	O
+individual	O
+-	O
+level	O
+data	O
+.	O
+
+It	O
+is	O
+also	O
+difficult	O
+to	O
+identify	O
+the	O
+component	O
+of	O
+productivity	O
+loss	O
+that	O
+is	O
+due	O
+to	O
+blindness	O
+,	O
+as	O
+this	O
+condition	O
+mainly	O
+affects	O
+older	O
+people	B
+,	O
+who	O
+may	O
+suffer	O
+from	O
+other	O
+comorbidities	O
+that	O
+restrict	O
+their	O
+employment	O
+opportunities	O
+or	O
+make	O
+them	O
+dependent	O
+on	O
+the	O
+care	O
+of	O
+others	O
+.	O
+
+The	O
+Cataract	O
+Impact	O
+Study	O
+was	O
+undertaken	O
+to	O
+assess	O
+the	O
+relationship	O
+between	O
+cataract	O
+visual	O
+impairment	O
+and	O
+"	O
+economic	O
+poverty	O
+"	O
+and	O
+quality	O
+of	O
+life	O
+,	O
+and	O
+to	O
+estimate	O
+the	O
+impact	O
+of	O
+cataract	O
+surgery	O
+on	O
+these	O
+factors	O
+in	O
+three	O
+low	O
+-	O
+income	O
+countries	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+current	O
+paper	O
+is	O
+to	O
+assess	O
+the	O
+association	O
+at	O
+baseline	O
+between	O
+visual	O
+impairment	O
+from	O
+cataract	O
+and	O
+household	O
+poverty	O
+(	O
+measured	O
+through	O
+consumption	O
+,	O
+asset	O
+ownership	O
+,	O
+and	O
+self	O
+-	O
+rated	O
+wealth	O
+)	O
+in	O
+a	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+in	O
+Kenya	O
+,	O
+the	O
+Philippines	O
+,	O
+and	O
+Bangladesh	O
+.	O
+
+Methods	O
+
+Setting	O
+
+Case	O
+and	O
+control	O
+participants	B
+were	O
+recruited	O
+from	O
+Nakuru	O
+district	O
+,	O
+Kenya	O
+(	O
+January	O
+-	O
+February	O
+,	O
+2005	O
+)	O
+;	O
+Negros	O
+island	O
+(	O
+May	O
+-	O
+June	O
+,	O
+2005	O
+)	O
+and	O
+Antique	O
+district	O
+(	O
+April	O
+-	O
+May	O
+,	O
+2006	O
+)	O
+,	O
+Philippines	O
+;	O
+and	O
+Satkhira	O
+district	O
+,	O
+Bangladesh	O
+(	O
+November	O
+-	O
+December	O
+,	O
+2005	O
+)	O
+.	O
+
+Selection	O
+of	O
+Cases	O
+and	O
+Controls	O
+
+Persons	B
+with	O
+cataract	O
+visual	O
+impairment	O
+(	O
+cases	O
+)	O
+and	O
+persons	B
+without	O
+(	O
+controls	O
+)	O
+were	O
+primarily	O
+recruited	O
+through	O
+a	O
+population	O
+-	O
+based	O
+survey	O
+of	O
+adults	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+[	O
+6	O
+-	O
+8	O
+]	O
+.	O
+
+Clusters	O
+of	O
+50	O
+people	B
+(	O
+regardless	O
+of	O
+visual	O
+impairment	O
+)	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+were	O
+selected	O
+through	O
+probability	O
+-	O
+proportionate	O
+to	O
+size	O
+sampling	O
+,	O
+using	O
+either	O
+the	O
+census	O
+(	O
+Philippines	O
+and	O
+Bangladesh	O
+)	O
+or	O
+electoral	O
+role	O
+(	O
+Kenya	O
+)	O
+as	O
+the	O
+sampling	O
+frame	O
+.	O
+
+Households	O
+within	O
+clusters	O
+were	O
+selected	O
+through	O
+a	O
+modification	O
+of	O
+compact	O
+segment	O
+sampling	O
+,	O
+whereby	O
+a	O
+map	O
+was	O
+drawn	O
+of	O
+the	O
+enumeration	O
+area	O
+that	O
+was	O
+divided	O
+into	O
+segments	O
+,	O
+each	O
+including	O
+approximately	O
+50	O
+people	B
+aged	O
+>	O
+=	O
+50	O
+y	O
+,	O
+and	O
+one	O
+segment	O
+was	O
+chosen	O
+at	O
+random	O
+[	O
+13	O
+]	O
+.	O
+
+Households	O
+in	O
+the	O
+segment	O
+were	O
+included	O
+sequentially	O
+until	O
+50	O
+people	B
+aged	O
+>	O
+=	O
+50	O
+y	O
+were	O
+identified	O
+.	O
+
+The	O
+surveys	O
+included	O
+3	O
+,	O
+503	O
+(	O
+93	O
+%	O
+response	O
+rate	O
+)	O
+people	B
+aged	O
+>	O
+=	O
+50	O
+y	O
+in	O
+Kenya	O
+,	O
+4	O
+,	O
+868	O
+(	O
+92	O
+%	O
+)	O
+in	O
+Bangladesh	O
+,	O
+2	O
+,	O
+774	O
+(	O
+76	O
+%	O
+)	O
+in	O
+Negros	O
+,	O
+and	O
+3	O
+,	O
+177	O
+(	O
+83	O
+%	O
+)	O
+in	O
+Antique	O
+.	O
+
+All	O
+people	B
+in	O
+the	O
+survey	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+underwent	O
+visual	O
+acuity	O
+(	O
+VA	O
+)	O
+testing	O
+and	O
+ophthalmic	O
+examination	O
+.	O
+
+VA	O
+was	O
+measured	O
+in	O
+full	O
+daylight	O
+with	O
+available	O
+spectacle	O
+correction	O
+with	O
+a	O
+Snellen	O
+tumbling	O
+"	O
+E	O
+"	O
+chart	O
+using	O
+optotype	O
+size	O
+6	O
+/	O
+18	O
+(	O
+20	O
+/	O
+60	O
+)	O
+on	O
+one	O
+side	O
+and	O
+size	O
+6	O
+/	O
+60	O
+(	O
+20	O
+/	O
+200	O
+)	O
+on	O
+the	O
+other	O
+side	O
+at	O
+6	O
+or	O
+3	O
+metres	O
+.	O
+
+If	O
+the	O
+VA	O
+was	O
+<	O
+6	O
+/	O
+18	O
+in	O
+either	O
+eye	O
+then	O
+pinhole	O
+vision	O
+was	O
+also	O
+measured	O
+.	O
+
+Participants	B
+with	O
+pinhole	O
+vision	O
+<	O
+6	O
+/	O
+18	O
+but	O
+>	O
+6	O
+/	O
+60	O
+in	O
+the	O
+better	O
+eye	O
+due	O
+to	O
+age	O
+-	O
+related	O
+cataract	O
+were	O
+given	O
+a	O
+second	O
+VA	O
+test	O
+using	O
+an	O
+"	O
+E	O
+"	O
+of	O
+size	O
+6	O
+/	O
+24	O
+.	O
+
+The	O
+ophthalmologist	O
+examined	O
+all	O
+eyes	O
+with	O
+a	O
+presenting	O
+VA	O
+<	O
+6	O
+/	O
+18	O
+with	O
+a	O
+torch	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+flashlight	O
+)	O
+,	O
+direct	O
+ophthalmoscope	O
+,	O
+and	O
+/	O
+or	O
+portable	O
+slit	O
+lamp	O
+.	O
+
+The	O
+principal	O
+cause	O
+of	O
+blindness	O
+or	O
+visual	O
+impairment	O
+was	O
+recorded	O
+,	O
+according	O
+to	O
+the	O
+WHO	O
+convention	O
+in	O
+which	O
+the	O
+major	O
+cause	O
+is	O
+assigned	O
+to	O
+the	O
+primary	O
+disorder	O
+or	O
+,	O
+if	O
+there	O
+are	O
+two	O
+existing	O
+primary	O
+disorders	O
+,	O
+to	O
+the	O
+one	O
+that	O
+is	O
+easiest	O
+to	O
+treat	O
+[	O
+14	O
+]	O
+.	O
+
+Survey	O
+participants	B
+were	O
+eligible	O
+for	O
+inclusion	O
+as	O
+cases	O
+if	O
+they	O
+were	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+with	O
+best	O
+corrected	O
+visual	O
+acuity	O
+<	O
+6	O
+/	O
+24	O
+in	O
+the	O
+better	O
+eye	O
+due	O
+to	O
+cataract	O
+,	O
+as	O
+diagnosed	O
+by	O
+an	O
+ophthalmologist	O
+.	O
+
+All	O
+eligible	O
+cases	O
+identified	O
+from	O
+these	O
+surveys	O
+were	O
+invited	O
+to	O
+participate	O
+in	O
+the	O
+study	O
+.	O
+
+Participants	B
+were	O
+eligible	O
+to	O
+be	O
+controls	O
+if	O
+they	O
+were	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+,	O
+did	O
+not	O
+have	O
+VA	O
+<	O
+6	O
+/	O
+24	O
+in	O
+the	O
+better	O
+eye	O
+due	O
+to	O
+cataract	O
+and	O
+did	O
+not	O
+live	O
+in	O
+the	O
+same	O
+household	O
+as	O
+a	O
+case	O
+.	O
+
+During	O
+the	O
+survey	O
+a	O
+list	O
+was	O
+maintained	O
+of	O
+all	O
+eligible	O
+controls	O
+,	O
+by	O
+age	O
+group	O
+(	O
+50	O
+-	O
+54	O
+,	O
+55	O
+-	O
+59	O
+,	O
+60	O
+-	O
+64	O
+,	O
+65	O
+-	O
+69	O
+,	O
+and	O
+>	O
+70	O
+)	O
+and	O
+sex	O
+.	O
+
+Whenever	O
+a	O
+case	O
+was	O
+identified	O
+,	O
+one	O
+age	O
+-	O
+and	O
+sex	O
+-	O
+matched	O
+control	O
+was	O
+randomly	O
+selected	O
+from	O
+the	O
+list	O
+for	O
+inclusion	O
+(	O
+or	O
+up	O
+to	O
+two	O
+controls	O
+in	O
+Bangladesh	O
+)	O
+.	O
+
+If	O
+no	O
+matching	O
+eligible	O
+controls	O
+had	O
+been	O
+identified	O
+in	O
+that	O
+cluster	O
+at	O
+that	O
+stage	O
+of	O
+the	O
+survey	O
+,	O
+then	O
+the	O
+next	O
+eligible	O
+control	O
+in	O
+the	O
+cluster	O
+was	O
+recruited	O
+.	O
+
+Because	O
+of	O
+logistical	O
+and	O
+time	O
+constraints	O
+,	O
+additional	O
+cases	O
+were	O
+also	O
+included	O
+through	O
+community	O
+-	O
+based	O
+case	O
+detection	O
+.	O
+
+In	O
+Kenya	O
+and	O
+Negros	O
+(	O
+Philippines	O
+)	O
+,	O
+clusters	O
+were	O
+randomly	O
+selected	O
+through	O
+probability	O
+proportionate	O
+to	O
+size	O
+using	O
+the	O
+same	O
+cluster	O
+sampling	O
+procedure	O
+after	O
+completion	O
+of	O
+the	O
+population	O
+-	O
+based	O
+survey	O
+.	O
+
+Clusters	O
+were	O
+visited	O
+in	O
+advance	O
+and	O
+asked	O
+that	O
+all	O
+people	B
+>	O
+=	O
+50	O
+y	O
+with	O
+vision	O
+problems	O
+come	O
+to	O
+a	O
+central	O
+point	O
+on	O
+a	O
+specified	O
+day	O
+,	O
+and	O
+that	O
+a	O
+list	O
+be	O
+made	O
+of	O
+people	B
+unable	O
+to	O
+attend	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+due	O
+to	O
+blindness	O
+or	O
+other	O
+physical	O
+disability	O
+)	O
+.	O
+
+After	O
+examining	O
+patients	B
+at	O
+the	O
+central	O
+point	O
+,	O
+the	O
+survey	O
+team	O
+then	O
+visited	O
+those	O
+unable	O
+to	O
+leave	O
+their	O
+houses	O
+.	O
+
+Any	O
+identified	O
+eligible	O
+cases	O
+that	O
+agreed	O
+to	O
+be	O
+part	O
+of	O
+the	O
+study	O
+were	O
+interviewed	O
+in	O
+their	O
+homes	O
+.	O
+
+In	O
+Bangladesh	O
+and	O
+Antique	O
+(	O
+Philippines	O
+)	O
+,	O
+community	O
+case	O
+detection	O
+was	O
+carried	O
+out	O
+simultaneously	O
+with	O
+the	O
+survey	O
+by	O
+two	O
+of	O
+the	O
+four	O
+teams	O
+,	O
+so	O
+that	O
+controls	O
+were	O
+included	O
+for	O
+these	O
+cases	O
+.	O
+
+Within	O
+each	O
+cluster	O
+from	O
+the	O
+survey	O
+,	O
+one	O
+interviewer	O
+was	O
+asked	O
+to	O
+be	O
+taken	O
+to	O
+two	O
+community	O
+members	O
+aged	O
+>	O
+=	O
+50	O
+y	O
+with	O
+eye	O
+problems	O
+,	O
+living	O
+within	O
+the	O
+cluster	O
+boundaries	O
+but	O
+not	O
+from	O
+the	O
+segments	O
+selected	O
+for	O
+the	O
+survey	O
+.	O
+
+If	O
+VA	O
+was	O
+<	O
+6	O
+/	O
+24	O
+with	O
+pinhole	O
+in	O
+the	O
+better	O
+eye	O
+,	O
+the	O
+ophthalmologist	O
+was	O
+called	O
+to	O
+carry	O
+out	O
+the	O
+full	O
+eye	O
+examination	O
+,	O
+and	O
+eligible	O
+cases	O
+were	O
+included	O
+in	O
+the	O
+study	O
+.	O
+
+For	O
+the	O
+purposes	O
+of	O
+the	O
+present	O
+analyses	O
+,	O
+control	O
+individuals	O
+with	O
+any	O
+visual	O
+impairment	O
+(	O
+VA	O
+<	O
+6	O
+/	O
+18	O
+in	O
+the	O
+better	O
+eye	O
+)	O
+were	O
+excluded	O
+(	O
+n	O
+=	O
+14	O
+in	O
+Kenya	O
+,	O
+n	O
+=	O
+53	O
+in	O
+Bangladesh	O
+,	O
+n	O
+=	O
+24	O
+in	O
+the	O
+Philippines	O
+)	O
+.	O
+
+Case	O
+and	O
+control	O
+participants	B
+who	O
+were	O
+significantly	O
+communication	O
+impaired	O
+(	O
+e	O
+.	O
+g	O
+.	O
+deafness	O
+,	O
+dementia	O
+,	O
+or	O
+psychiatric	O
+disease	O
+)	O
+were	O
+excluded	O
+(	O
+fewer	O
+than	O
+five	O
+per	O
+country	O
+)	O
+,	O
+and	O
+one	O
+case	O
+was	O
+excluded	O
+in	O
+the	O
+Philippines	O
+because	O
+of	O
+missing	O
+age	O
+data	O
+.	O
+
+One	O
+household	O
+had	O
+two	O
+eligible	O
+cases	O
+(	O
+Kenya	O
+)	O
+,	O
+and	O
+one	O
+of	O
+these	O
+participants	B
+was	O
+excluded	O
+for	O
+the	O
+poverty	O
+analyses	O
+as	O
+poverty	O
+was	O
+assessed	O
+through	O
+household	O
+level	O
+indicators	O
+(	O
+see	O
+below	O
+)	O
+.	O
+
+In	O
+total	O
+,	O
+147	O
+cases	O
+(	O
+82	O
+from	O
+the	O
+survey	O
+and	O
+65	O
+from	O
+case	O
+detection	O
+)	O
+and	O
+79	O
+controls	O
+were	O
+included	O
+in	O
+Kenya	O
+;	O
+217	O
+cases	O
+(	O
+162	O
+from	O
+survey	O
+and	O
+55	O
+from	O
+case	O
+detection	O
+)	O
+and	O
+280	O
+controls	O
+in	O
+Bangladesh	O
+;	O
+and	O
+238	O
+cases	O
+(	O
+146	O
+survey	O
+and	O
+92	O
+case	O
+detection	O
+)	O
+and	O
+180	O
+controls	O
+in	O
+the	O
+Philippines	O
+.	O
+
+Data	O
+Collection	O
+
+All	O
+case	O
+and	O
+control	O
+participants	B
+were	O
+interviewed	O
+in	O
+their	O
+homes	O
+by	O
+trained	O
+interviewers	O
+in	O
+the	O
+local	O
+language	O
+.	O
+
+Each	O
+interview	O
+lasted	O
+approximately	O
+1	O
+h	O
+.	O
+
+Measures	O
+of	O
+poverty	O
+.	O
+
+Poverty	O
+was	O
+measured	O
+through	O
+(	O
+a	O
+)	O
+monthly	O
+per	O
+capita	O
+expenditure	O
+(	O
+PCE	O
+)	O
+to	O
+indicate	O
+consumption	O
+,	O
+(	O
+b	O
+)	O
+asset	O
+ownership	O
+,	O
+and	O
+(	O
+c	O
+)	O
+self	O
+-	O
+rated	O
+wealth	O
+.	O
+
+The	O
+economic	O
+part	O
+of	O
+the	O
+questionnaires	O
+was	O
+adapted	O
+through	O
+interviews	O
+,	O
+focus	O
+group	O
+discussions	O
+,	O
+and	O
+pilot	O
+testing	O
+in	O
+each	O
+country	O
+to	O
+ensure	O
+local	O
+relevance	O
+.	O
+
+The	O
+person	B
+primarily	O
+responsible	O
+for	O
+household	O
+finances	O
+(	O
+which	O
+may	O
+have	O
+been	O
+the	O
+case	O
+/	O
+control	O
+or	O
+another	O
+household	O
+member	O
+)	O
+was	O
+interviewed	O
+to	O
+assess	O
+PCE	O
+and	O
+assets	O
+.	O
+
+PCE	O
+was	O
+measured	O
+using	O
+methods	O
+based	O
+on	O
+the	O
+World	O
+Bank	O
+'	O
+s	O
+Living	O
+Standards	O
+Measurement	O
+Study	O
+[	O
+15	O
+]	O
+.	O
+
+Items	O
+were	O
+included	O
+on	O
+food	O
+(	O
+42	O
+-	O
+52	O
+items	O
+per	O
+country	O
+)	O
+,	O
+education	O
+(	O
+three	O
+items	O
+)	O
+,	O
+health	O
+(	O
+five	O
+items	O
+)	O
+,	O
+household	O
+expenses	O
+(	O
+nine	O
+items	O
+)	O
+,	O
+and	O
+personal	O
+expenses	O
+(	O
+21	O
+or	O
+22	O
+items	O
+)	O
+.	O
+
+In	O
+total	O
+,	O
+85	O
+items	O
+were	O
+included	O
+in	O
+the	O
+questionnaire	O
+in	O
+Kenya	O
+,	O
+90	O
+in	O
+the	O
+Philippines	O
+,	O
+and	O
+79	O
+in	O
+Bangladesh	O
+.	O
+
+The	O
+informant	O
+was	O
+asked	O
+to	O
+recall	O
+the	O
+monetary	O
+value	O
+of	O
+food	O
+that	O
+was	O
+purchased	O
+,	O
+consumed	O
+from	O
+home	O
+production	O
+,	O
+or	O
+received	O
+as	O
+payment	O
+in	O
+kind	O
+or	O
+as	O
+gifts	O
+.	O
+
+Consumption	O
+was	O
+assessed	O
+over	O
+a	O
+1	O
+-	O
+wk	O
+period	O
+for	O
+frequently	O
+consumed	O
+items	O
+,	O
+and	O
+this	O
+was	O
+scaled	O
+up	O
+to	O
+estimate	O
+monthly	O
+consumption	O
+.	O
+
+The	O
+amount	O
+consumed	O
+monthly	O
+was	O
+assessed	O
+for	O
+items	O
+that	O
+were	O
+consumed	O
+more	O
+rarely	O
+.	O
+
+Monthly	O
+rent	O
+was	O
+recorded	O
+among	O
+households	O
+who	O
+rented	O
+,	O
+and	O
+households	O
+who	O
+owned	O
+their	O
+property	O
+were	O
+asked	O
+to	O
+estimate	O
+the	O
+amount	O
+that	O
+they	O
+could	O
+charge	O
+in	O
+rent	O
+per	O
+month	O
+.	O
+
+The	O
+consumption	O
+on	O
+all	O
+items	O
+was	O
+summed	O
+to	O
+calculate	O
+total	O
+monthly	O
+household	O
+consumption	O
+,	O
+and	O
+this	O
+was	O
+converted	O
+to	O
+United	O
+States	O
+dollars	O
+(	O
+US	O
+$	O
+)	O
+at	O
+the	O
+2005	O
+exchange	O
+rate	O
+(	O
+$	O
+1	O
+=	O
+76	O
+Kenya	O
+shillings	O
+,	O
+64	O
+Bangladesh	O
+taka	O
+,	O
+55	O
+Philippine	O
+pesos	O
+)	O
+.	O
+
+Total	O
+monthly	O
+household	O
+consumption	O
+was	O
+divided	O
+by	O
+the	O
+number	O
+of	O
+household	O
+members	O
+to	O
+calculate	O
+monthly	O
+PCE	O
+for	O
+the	O
+household	O
+.	O
+
+The	O
+household	O
+informant	O
+was	O
+also	O
+asked	O
+about	O
+the	O
+number	O
+and	O
+type	O
+of	O
+context	O
+-	O
+specific	O
+assets	O
+owned	O
+by	O
+the	O
+household	O
+,	O
+including	O
+different	O
+types	O
+of	O
+furniture	O
+,	O
+electrical	O
+equipment	O
+,	O
+cattle	B
+,	O
+and	O
+vehicles	O
+.	O
+
+Information	O
+was	O
+collected	O
+on	O
+household	O
+characteristics	O
+,	O
+including	O
+the	O
+building	O
+material	O
+of	O
+the	O
+floor	O
+,	O
+roof	O
+,	O
+and	O
+walls	O
+;	O
+type	O
+of	O
+toilet	O
+;	O
+and	O
+the	O
+number	O
+of	O
+rooms	O
+.	O
+
+Self	O
+-	O
+rated	O
+wealth	O
+was	O
+assessed	O
+by	O
+asking	O
+the	O
+household	O
+informant	O
+to	O
+rank	O
+the	O
+household	O
+'	O
+s	O
+wealth	O
+relative	O
+to	O
+others	O
+in	O
+the	O
+community	O
+on	O
+a	O
+scale	O
+from	O
+1	O
+(	O
+poorest	O
+)	O
+to	O
+10	O
+(	O
+richest	O
+)	O
+.	O
+
+Covariates	O
+.	O
+
+Case	O
+and	O
+control	O
+individuals	O
+were	O
+interviewed	O
+about	O
+standard	O
+sociodemographic	O
+indicators	O
+,	O
+including	O
+household	O
+composition	O
+,	O
+education	O
+,	O
+and	O
+employment	O
+.	O
+
+Information	O
+was	O
+collected	O
+on	O
+vision	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+using	O
+the	O
+World	O
+Health	O
+Organization	O
+Prevention	O
+of	O
+Blindness	O
+and	O
+Deafness	O
+20	O
+-	O
+item	O
+Visual	O
+Functioning	O
+Questionnaire	O
+[	O
+16	O
+,	O
+17	O
+]	O
+,	O
+and	O
+health	O
+-	O
+related	O
+quality	O
+of	O
+life	O
+was	O
+assessed	O
+using	O
+items	O
+from	O
+the	O
+European	O
+Quality	O
+of	O
+Life	O
+Questionnaire	O
+[	O
+18	O
+]	O
+.	O
+
+Detailed	O
+time	O
+-	O
+use	O
+data	O
+were	O
+collected	O
+using	O
+methods	O
+based	O
+on	O
+the	O
+World	O
+Bank	O
+'	O
+s	O
+Living	O
+Standards	O
+Measurement	O
+Study	O
+[	O
+15	O
+]	O
+.	O
+
+Training	O
+and	O
+Fieldwork	O
+
+Interviewers	O
+were	O
+trained	O
+for	O
+1	O
+wk	O
+,	O
+including	O
+2	O
+d	O
+of	O
+pilot	O
+testing	O
+.	O
+
+Attempts	O
+were	O
+made	O
+to	O
+minimise	O
+measurement	O
+bias	O
+by	O
+emphasising	O
+the	O
+need	O
+for	O
+consistency	O
+in	O
+data	O
+collection	O
+among	O
+cases	O
+and	O
+controls	O
+.	O
+
+The	O
+questionnaires	O
+were	O
+translated	O
+into	O
+the	O
+local	O
+languages	O
+(	O
+three	O
+in	O
+Kenya	O
+,	O
+three	O
+in	O
+the	O
+Philippines	O
+,	O
+and	O
+one	O
+in	O
+Bangladesh	O
+)	O
+and	O
+back	O
+-	O
+translated	O
+by	O
+independent	O
+translators	O
+(	O
+one	O
+for	O
+each	O
+language	O
+)	O
+who	O
+were	O
+also	O
+asked	O
+to	O
+comment	O
+on	O
+appropriateness	O
+of	O
+language	O
+used	O
+for	O
+the	O
+target	O
+population	O
+.	O
+
+A	O
+review	O
+was	O
+held	O
+to	O
+discuss	O
+differences	O
+in	O
+translation	O
+and	O
+modify	O
+accordingly	O
+.	O
+
+The	O
+questionnaire	O
+was	O
+piloted	O
+in	O
+each	O
+setting	O
+and	O
+small	O
+modifications	O
+to	O
+wording	O
+of	O
+some	O
+items	O
+were	O
+made	O
+,	O
+where	O
+appropriate	O
+,	O
+to	O
+ensure	O
+local	O
+understanding	O
+.	O
+
+Teams	O
+were	O
+accompanied	O
+by	O
+a	O
+field	O
+supervisor	O
+at	O
+least	O
+1	O
+d	O
+per	O
+wk	O
+to	O
+ensure	O
+that	O
+high	O
+quality	O
+was	O
+maintained	O
+and	O
+interviews	O
+were	O
+observed	O
+randomly	O
+throughout	O
+the	O
+study	O
+.	O
+
+Statistical	O
+Analysis	O
+
+Microsoft	O
+Access	O
+was	O
+used	O
+for	O
+data	O
+entry	O
+,	O
+and	O
+all	O
+data	O
+were	O
+double	O
+entered	O
+and	O
+validated	O
+.	O
+
+Analyses	O
+were	O
+undertaken	O
+in	O
+SAS	O
+version	O
+8	O
+.	O
+2	O
+.	O
+
+The	O
+mean	O
+and	O
+range	O
+of	O
+each	O
+expenditure	O
+item	O
+was	O
+calculated	O
+to	O
+assess	O
+whether	O
+answers	O
+were	O
+plausible	O
+,	O
+and	O
+to	O
+identify	O
+and	O
+exclude	O
+gross	O
+outliers	O
+(	O
+none	O
+identified	O
+)	O
+.	O
+
+Rental	O
+equivalents	O
+were	O
+imputed	O
+based	O
+on	O
+household	O
+characteristics	O
+and	O
+non	O
+-	O
+rent	O
+expenditure	O
+for	O
+households	O
+where	O
+these	O
+estimates	O
+were	O
+missing	O
+or	O
+unreasonably	O
+low	O
+(	O
+<	O
+$	O
+1	O
+per	O
+mo	O
+)	O
+(	O
+four	O
+in	O
+Kenya	O
+,	O
+three	O
+in	O
+Bangladesh	O
+,	O
+18	O
+in	O
+the	O
+Philippines	O
+)	O
+.	O
+
+Total	O
+monthly	O
+household	O
+consumption	O
+was	O
+divided	O
+by	O
+the	O
+number	O
+of	O
+household	O
+members	O
+to	O
+calculate	O
+per	O
+capita	O
+household	O
+expenditure	O
+.	O
+
+Per	O
+capita	O
+household	O
+expenditure	O
+was	O
+divided	O
+into	O
+quartiles	O
+,	O
+separately	O
+for	O
+each	O
+country	O
+,	O
+based	O
+on	O
+the	O
+distribution	O
+of	O
+the	O
+data	O
+for	O
+the	O
+case	O
+and	O
+control	O
+participants	B
+combined	O
+.	O
+
+Households	O
+with	O
+incomplete	O
+expenditure	O
+data	O
+were	O
+excluded	O
+from	O
+analyses	O
+(	O
+five	O
+cases	O
+and	O
+four	O
+controls	O
+in	O
+Kenya	O
+;	O
+one	O
+case	O
+and	O
+one	O
+control	O
+in	O
+Bangladesh	O
+)	O
+.	O
+
+A	O
+relative	O
+index	O
+of	O
+household	O
+assets	O
+was	O
+derived	O
+using	O
+principal	O
+components	O
+analysis	O
+(	O
+PCA	O
+)	O
+to	O
+determine	O
+weights	O
+for	O
+a	O
+list	O
+of	O
+assets	O
+and	O
+wealth	O
+indicators	O
+[	O
+19	O
+]	O
+.	O
+
+Variables	O
+entered	O
+into	O
+the	O
+PCA	O
+included	O
+building	O
+materials	O
+of	O
+the	O
+house	O
+,	O
+ownership	O
+of	O
+ten	O
+household	O
+assets	O
+,	O
+animal	O
+ownership	O
+,	O
+and	O
+education	O
+of	O
+the	O
+head	O
+of	O
+the	O
+household	O
+.	O
+
+The	O
+derived	O
+index	O
+was	O
+divided	O
+into	O
+quartiles	O
+from	O
+poorest	O
+(	O
+lowest	O
+socioeconomic	O
+status	O
+[	O
+SES	O
+]	O
+index	O
+)	O
+to	O
+least	O
+poor	O
+(	O
+highest	O
+SES	O
+index	O
+)	O
+.	O
+
+PCA	O
+analyses	O
+were	O
+undertaken	O
+separately	O
+for	O
+each	O
+country	O
+.	O
+
+The	O
+means	O
+of	O
+the	O
+poverty	O
+variables	O
+were	O
+first	O
+compared	O
+for	O
+cases	O
+recruited	O
+through	O
+the	O
+two	O
+different	O
+methods	O
+,	O
+and	O
+then	O
+from	O
+cases	O
+and	O
+controls	O
+using	O
+t	O
+-	O
+tests	O
+for	O
+continuous	O
+variables	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+PCE	O
+and	O
+assets	O
+)	O
+.	O
+
+For	O
+categorical	O
+variables	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+household	O
+rank	O
+)	O
+we	O
+used	O
+the	O
+Mann	O
+-	O
+Whitney	O
+test	O
+and	O
+presented	O
+medians	O
+and	O
+interquartile	O
+ranges	O
+.	O
+
+PCE	O
+was	O
+highly	O
+skewed	O
+and	O
+therefore	O
+was	O
+log	O
+transformed	O
+for	O
+the	O
+t	O
+-	O
+tests	O
+.	O
+
+The	O
+two	O
+-	O
+way	O
+correlations	O
+were	O
+calculated	O
+between	O
+PCE	O
+,	O
+assets	O
+,	O
+and	O
+household	O
+rank	O
+,	O
+in	O
+turn	O
+.	O
+
+Logistic	O
+regression	O
+analyses	O
+were	O
+undertaken	O
+separately	O
+for	O
+each	O
+country	O
+,	O
+assessing	O
+the	O
+association	O
+between	O
+case	O
+/	O
+control	O
+status	O
+and	O
+sociodemographic	O
+and	O
+poverty	O
+variables	O
+.	O
+
+Conditional	O
+logistic	O
+regression	O
+was	O
+not	O
+undertaken	O
+,	O
+since	O
+the	O
+matching	O
+was	O
+incomplete	O
+,	O
+so	O
+all	O
+analyses	O
+were	O
+adjusted	O
+for	O
+the	O
+matching	O
+variables	O
+(	O
+age	O
+,	O
+sex	O
+,	O
+and	O
+rural	O
+/	O
+urban	O
+location	O
+)	O
+.	O
+
+Likelihood	O
+ratio	O
+tests	O
+were	O
+undertaken	O
+to	O
+assess	O
+the	O
+significance	O
+of	O
+adding	O
+covariates	O
+with	O
+more	O
+than	O
+two	O
+levels	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+age	O
+groups	O
+,	O
+self	O
+-	O
+rated	O
+health	O
+groups	O
+)	O
+to	O
+the	O
+model	O
+.	O
+
+Tests	O
+for	O
+trend	O
+were	O
+undertaken	O
+across	O
+quartiles	O
+of	O
+the	O
+poverty	O
+variables	O
+and	O
+assessed	O
+using	O
+the	O
+p	O
+-	O
+value	O
+for	O
+trend	O
+.	O
+
+Analyses	O
+were	O
+also	O
+conducted	O
+adjusting	O
+for	O
+the	O
+logistic	O
+regression	O
+analyses	O
+for	O
+poverty	O
+by	O
+social	O
+support	O
+indicators	O
+(	O
+marital	O
+status	O
+and	O
+household	O
+size	O
+)	O
+and	O
+self	O
+-	O
+rated	O
+health	O
+,	O
+since	O
+these	O
+variables	O
+may	O
+confound	O
+the	O
+association	O
+between	O
+cataract	O
+visual	O
+impairment	O
+and	O
+poverty	O
+.	O
+
+Analyses	O
+from	O
+the	O
+Philippines	O
+were	O
+also	O
+adjusted	O
+for	O
+study	O
+site	O
+,	O
+since	O
+data	O
+were	O
+obtained	O
+from	O
+two	O
+settings	O
+(	O
+Negros	O
+and	O
+Antique	O
+)	O
+.	O
+
+An	O
+attempt	O
+was	O
+made	O
+to	O
+disentangle	O
+the	O
+relationship	O
+between	O
+poverty	O
+and	O
+cataract	O
+by	O
+stratifying	O
+the	O
+analyses	O
+by	O
+age	O
+,	O
+sex	O
+,	O
+and	O
+level	O
+of	O
+visual	O
+impairment	O
+among	O
+the	O
+cases	O
+.	O
+
+Ethical	O
+Approval	O
+
+Informed	O
+signed	O
+or	O
+thumb	O
+-	O
+printed	O
+consent	O
+was	O
+obtained	O
+from	O
+all	O
+cases	O
+and	O
+controls	O
+.	O
+
+In	O
+Kenya	O
+and	O
+Bangladesh	O
+all	O
+cases	O
+were	O
+offered	O
+free	O
+cataract	O
+surgery	O
+at	O
+the	O
+local	O
+hospital	O
+,	O
+with	O
+free	O
+transport	O
+.	O
+
+In	O
+the	O
+Philippines	O
+,	O
+patients	B
+were	O
+referred	O
+for	O
+surgery	O
+,	O
+which	O
+was	O
+subsidised	O
+for	O
+patients	B
+who	O
+could	O
+not	O
+afford	O
+the	O
+fee	O
+.	O
+
+Ethical	O
+approval	O
+for	O
+this	O
+study	O
+was	O
+obtained	O
+from	O
+the	O
+ethics	O
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+La	O
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+,	O
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+,	O
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+
+This	O
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+
+Results	O
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+Sociodemographic	O
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+Case	O
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+However	O
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+Cases	O
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+Cases	O
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+,	O
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+)	O
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+6	O
+,	O
+1	O
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+1	O
+-	O
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+)	O
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+3	O
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+3	O
+,	O
+2	O
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+3	O
+)	O
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+
+Summary	O
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+All	O
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+The	O
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+$	O
+1	O
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+26	O
+.	O
+4	O
+(	O
+standard	O
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+[	O
+SD	O
+]	O
+=	O
+US	O
+$	O
+34	O
+.	O
+9	O
+)	O
+in	O
+Kenya	O
+,	O
+US	O
+$	O
+21	O
+.	O
+7	O
+(	O
+US	O
+$	O
+48	O
+.	O
+0	O
+)	O
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+US	O
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+26	O
+.	O
+1	O
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+5	O
+)	O
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+The	O
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+47	O
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+The	O
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+,	O
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+77	O
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+An	O
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+The	O
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+,	O
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+24	O
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+Self	O
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+)	O
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+(	O
+43	O
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+)	O
+,	O
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+(	O
+64	O
+%	O
+)	O
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+4	O
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+1	O
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+,	O
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+terms	O
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+
+The	O
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+,	O
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+(	O
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+0	O
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+)	O
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+the	O
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+
+Economic	O
+and	O
+Household	O
+Characteristics	O
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+Cases	O
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+
+There	O
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+no	O
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+,	O
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+,	O
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+-	O
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+Consequently	O
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+Cases	O
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+,	O
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+The	O
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+=	O
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+The	O
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+Self	O
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+4	O
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+)	O
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+)	O
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+
+There	O
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+The	O
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+.	O
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+,	O
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+<	O
+15	O
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+=	O
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+)	O
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+
+Patterns	O
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+Cases	O
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+
+Figure	O
+1	O
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+Monthly	O
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+There	O
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+
+Substantial	O
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+
+Similar	O
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+
+These	O
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+
+Multivariate	O
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+Impairment	O
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+Multivariate	O
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+
+Cases	O
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+-	O
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+,	O
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+,	O
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+7	O
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+
+In	O
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+-	O
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+,	O
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+after	O
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+-	O
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+and	O
+social	O
+support	O
+indicators	O
+.	O
+
+A	O
+similar	O
+pattern	O
+was	O
+observed	O
+for	O
+the	O
+relationship	O
+between	O
+case	O
+-	O
+control	O
+status	O
+and	O
+asset	O
+ownership	O
+.	O
+
+Cases	O
+were	O
+significantly	O
+more	O
+likely	O
+to	O
+be	O
+in	O
+the	O
+lowest	O
+quartile	O
+of	O
+asset	O
+ownership	O
+rather	O
+than	O
+the	O
+highest	O
+quartile	O
+compared	O
+to	O
+controls	O
+in	O
+Kenya	O
+(	O
+3	O
+.	O
+7	O
+,	O
+1	O
+.	O
+4	O
+-	O
+9	O
+.	O
+6	O
+)	O
+,	O
+Bangladesh	O
+(	O
+2	O
+.	O
+6	O
+,	O
+1	O
+.	O
+5	O
+-	O
+4	O
+.	O
+4	O
+)	O
+,	O
+and	O
+the	O
+Philippines	O
+(	O
+2	O
+.	O
+1	O
+,	O
+1	O
+.	O
+1	O
+-	O
+3	O
+.	O
+8	O
+)	O
+.	O
+
+Cases	O
+were	O
+also	O
+significantly	O
+more	O
+likely	O
+to	O
+be	O
+in	O
+the	O
+lowest	O
+quartile	O
+of	O
+household	O
+rank	O
+rather	O
+than	O
+the	O
+highest	O
+,	O
+compared	O
+to	O
+controls	O
+in	O
+Kenya	O
+(	O
+3	O
+.	O
+5	O
+,	O
+1	O
+.	O
+5	O
+-	O
+8	O
+.	O
+0	O
+)	O
+,	O
+Bangladesh	O
+(	O
+2	O
+.	O
+7	O
+,	O
+1	O
+.	O
+6	O
+-	O
+4	O
+.	O
+7	O
+)	O
+and	O
+the	O
+Philippines	O
+(	O
+2	O
+.	O
+3	O
+,	O
+1	O
+.	O
+1	O
+-	O
+4	O
+.	O
+8	O
+)	O
+.	O
+
+The	O
+associations	O
+with	O
+assets	O
+and	O
+household	O
+rank	O
+also	O
+showed	O
+a	O
+significant	O
+dose	O
+-	O
+response	O
+relationship	O
+,	O
+and	O
+the	O
+associations	O
+were	O
+largely	O
+unchanged	O
+after	O
+adjustment	O
+for	O
+self	O
+-	O
+rated	O
+health	O
+and	O
+social	O
+support	O
+indicators	O
+.	O
+
+In	O
+Kenya	O
+and	O
+Bangladesh	O
+the	O
+relationship	O
+between	O
+PCE	O
+and	O
+case	O
+status	O
+was	O
+somewhat	O
+weaker	O
+than	O
+for	O
+the	O
+other	O
+measures	O
+of	O
+poverty	O
+,	O
+while	O
+the	O
+reverse	O
+was	O
+true	O
+in	O
+the	O
+Philippines	O
+.	O
+
+Stratifying	O
+the	O
+association	O
+between	O
+PCE	O
+and	O
+cataract	O
+visual	O
+impairment	O
+by	O
+level	O
+of	O
+visual	O
+impairment	O
+showed	O
+an	O
+inconsistent	O
+pattern	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+In	O
+Kenya	O
+,	O
+the	O
+association	O
+with	O
+low	O
+PCE	O
+was	O
+somewhat	O
+stronger	O
+comparing	O
+cataract	O
+blind	O
+cases	O
+to	O
+controls	O
+(	O
+OR	O
+3	O
+.	O
+1	O
+,	O
+95	O
+%	O
+CI	O
+0	O
+.	O
+9	O
+-	O
+10	O
+.	O
+8	O
+)	O
+than	O
+comparing	O
+moderate	O
+visually	O
+impaired	O
+cases	O
+to	O
+controls	O
+(	O
+1	O
+.	O
+8	O
+,	O
+0	O
+.	O
+6	O
+-	O
+5	O
+.	O
+4	O
+)	O
+,	O
+while	O
+this	O
+pattern	O
+was	O
+reversed	O
+in	O
+Bangladesh	O
+(	O
+blind	O
+cases	O
+versus	O
+controls	O
+:	O
+1	O
+.	O
+8	O
+,	O
+1	O
+.	O
+0	O
+-	O
+3	O
+.	O
+4	O
+;	O
+moderately	O
+visually	O
+impaired	O
+cases	O
+versus	O
+controls	O
+:	O
+3	O
+.	O
+1	O
+,	O
+1	O
+.	O
+3	O
+-	O
+7	O
+.	O
+2	O
+)	O
+.	O
+
+In	O
+the	O
+Philippines	O
+the	O
+association	O
+with	O
+low	O
+PCE	O
+was	O
+strongest	O
+comparing	O
+severely	O
+visually	O
+impaired	O
+cases	O
+to	O
+controls	O
+(	O
+5	O
+.	O
+9	O
+,	O
+2	O
+.	O
+0	O
+-	O
+17	O
+.	O
+6	O
+)	O
+.	O
+
+The	O
+association	O
+between	O
+cataract	O
+visual	O
+impairment	O
+and	O
+PCE	O
+was	O
+stronger	O
+among	O
+men	B
+than	O
+women	B
+in	O
+Bangladesh	O
+and	O
+the	O
+Philippines	O
+,	O
+while	O
+the	O
+reverse	O
+was	O
+true	O
+in	O
+Kenya	O
+(	O
+Table	O
+5	O
+)	O
+.	O
+
+In	O
+Kenya	O
+and	O
+the	O
+Philippines	O
+the	O
+strongest	O
+association	O
+between	O
+cataract	O
+and	O
+PCE	O
+was	O
+among	O
+people	B
+aged	O
+70	O
+-	O
+79	O
+y	O
+,	O
+while	O
+in	O
+Bangladesh	O
+the	O
+strongest	O
+effect	O
+was	O
+in	O
+people	B
+aged	O
+over	O
+80	O
+y	O
+.	O
+
+Stratifying	O
+the	O
+association	O
+between	O
+assets	O
+and	O
+household	O
+rank	O
+with	O
+cataract	O
+by	O
+level	O
+of	O
+visual	O
+impairment	O
+,	O
+sex	O
+,	O
+or	O
+age	O
+broadly	O
+repeated	O
+these	O
+findings	O
+,	O
+and	O
+generally	O
+supported	O
+the	O
+lack	O
+of	O
+consistent	O
+pattern	O
+(	O
+unpublished	O
+data	O
+)	O
+.	O
+
+Discussion	O
+
+This	O
+large	O
+,	O
+multicentre	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+provides	O
+evidence	O
+that	O
+people	B
+with	O
+visual	O
+impairment	O
+from	O
+cataract	O
+are	O
+poorer	O
+than	O
+control	O
+participants	B
+with	O
+normal	O
+vision	O
+matched	O
+for	O
+age	O
+and	O
+sex	O
+.	O
+
+This	O
+pattern	O
+was	O
+evident	O
+whether	O
+poverty	O
+was	O
+measured	O
+in	O
+terms	O
+of	O
+PCE	O
+,	O
+assets	O
+,	O
+or	O
+self	O
+-	O
+rated	O
+wealth	O
+.	O
+
+Marital	O
+status	O
+seemed	O
+to	O
+be	O
+protective	O
+for	O
+cataract	O
+visual	O
+impairment	O
+,	O
+possibly	O
+indicating	O
+the	O
+role	O
+of	O
+social	O
+support	O
+in	O
+health	O
+-	O
+seeking	O
+behaviour	O
+.	O
+
+Reduced	O
+self	O
+-	O
+rated	O
+health	O
+was	O
+also	O
+strongly	O
+related	O
+to	O
+cataract	O
+visual	O
+impairment	O
+.	O
+
+This	O
+demonstrates	O
+the	O
+impact	O
+of	O
+poor	O
+vision	O
+on	O
+overall	O
+assessments	O
+of	O
+health	O
+and	O
+supports	O
+our	O
+previous	O
+finding	O
+of	O
+a	O
+relationship	O
+between	O
+cataract	O
+and	O
+quality	O
+of	O
+life	O
+[	O
+17	O
+]	O
+.	O
+
+Adjustment	O
+for	O
+marital	O
+status	O
+and	O
+self	O
+-	O
+rated	O
+health	O
+did	O
+not	O
+entirely	O
+explain	O
+the	O
+association	O
+between	O
+poverty	O
+and	O
+cataract	O
+visual	O
+impairment	O
+,	O
+suggesting	O
+that	O
+it	O
+operated	O
+through	O
+other	O
+pathways	O
+.	O
+
+Visual	O
+impairment	O
+could	O
+cause	O
+poverty	O
+through	O
+reduced	O
+employment	O
+opportunities	O
+.	O
+
+We	O
+might	O
+therefore	O
+expect	O
+to	O
+see	O
+a	O
+stronger	O
+relationship	O
+between	O
+cataract	O
+and	O
+poverty	O
+among	O
+the	O
+blind	O
+case	O
+participants	B
+who	O
+may	O
+have	O
+fewer	O
+employment	O
+opportunities	O
+than	O
+among	O
+those	O
+less	O
+impaired	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+moderate	O
+visual	O
+impairment	O
+)	O
+.	O
+
+Poverty	O
+may	O
+also	O
+cause	O
+visual	O
+impairment	O
+through	O
+restricted	O
+access	O
+to	O
+cataract	O
+surgery	O
+.	O
+
+In	O
+this	O
+case	O
+we	O
+would	O
+expect	O
+to	O
+see	O
+a	O
+stronger	O
+relationship	O
+between	O
+poverty	O
+and	O
+less	O
+severely	O
+affected	O
+cases	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+moderate	O
+visual	O
+impairment	O
+)	O
+,	O
+as	O
+poor	O
+families	O
+may	O
+allocate	O
+money	O
+for	O
+surgery	O
+on	O
+members	O
+who	O
+are	O
+blind	O
+from	O
+cataract	O
+,	O
+so	O
+that	O
+poverty	O
+mainly	O
+restricts	O
+access	O
+to	O
+surgery	O
+among	O
+people	B
+who	O
+are	O
+moderately	O
+visually	O
+impaired	O
+.	O
+
+The	O
+relationships	O
+that	O
+we	O
+observed	O
+between	O
+level	O
+of	O
+visual	O
+impairment	O
+and	O
+cataract	O
+were	O
+inconsistent	O
+across	O
+the	O
+three	O
+settings	O
+.	O
+
+Perhaps	O
+this	O
+shows	O
+that	O
+both	O
+pathways	O
+were	O
+operating	O
+or	O
+that	O
+the	O
+dynamics	O
+of	O
+the	O
+relationship	O
+between	O
+poverty	O
+and	O
+blindness	O
+vary	O
+in	O
+different	O
+settings	O
+.	O
+
+Levels	O
+of	O
+literacy	O
+and	O
+education	O
+were	O
+lower	O
+among	O
+cases	O
+than	O
+controls	O
+.	O
+
+These	O
+long	O
+-	O
+term	O
+indicators	O
+of	O
+disadvantage	O
+are	O
+unlikely	O
+to	O
+have	O
+changed	O
+after	O
+the	O
+onset	O
+of	O
+cataract	O
+.	O
+
+This	O
+observation	O
+provides	O
+some	O
+evidence	O
+that	O
+poverty	O
+preceded	O
+blindness	O
+in	O
+our	O
+study	O
+participants	B
+.	O
+
+It	O
+is	O
+frequently	O
+asserted	O
+that	O
+blindness	O
+is	O
+both	O
+a	O
+cause	O
+and	O
+consequence	O
+of	O
+poverty	O
+,	O
+but	O
+there	O
+are	O
+few	O
+empirical	O
+data	O
+to	O
+support	O
+this	O
+claim	O
+.	O
+
+Globally	O
+,	O
+the	O
+prevalence	O
+of	O
+blindness	O
+is	O
+five	O
+-	O
+fold	O
+higher	O
+in	O
+poor	O
+than	O
+rich	O
+countries	O
+[	O
+2	O
+]	O
+,	O
+and	O
+data	O
+from	O
+Pakistan	O
+and	O
+India	O
+suggest	O
+that	O
+within	O
+countries	O
+the	O
+poor	O
+are	O
+more	O
+likely	O
+to	O
+be	O
+blind	O
+[	O
+3	O
+,	O
+4	O
+]	O
+.	O
+
+Some	O
+blinding	O
+conditions	O
+are	O
+a	O
+direct	O
+consequence	O
+of	O
+poverty	O
+,	O
+notably	O
+trachoma	O
+,	O
+which	O
+thrives	O
+in	O
+poor	O
+areas	O
+lacking	O
+water	O
+and	O
+sanitation	O
+[	O
+20	O
+]	O
+.	O
+
+Other	O
+blinding	O
+diseases	O
+clearly	O
+contribute	O
+to	O
+poverty	O
+,	O
+such	O
+as	O
+onchocerciasis	O
+,	O
+which	O
+results	O
+in	O
+the	O
+abandonment	O
+of	O
+the	O
+fertile	O
+areas	O
+near	O
+to	O
+the	O
+rivers	O
+where	O
+the	O
+disease	O
+vector	O
+thrives	O
+[	O
+9	O
+]	O
+.	O
+
+A	O
+larger	O
+literature	O
+shows	O
+that	O
+poor	O
+people	B
+are	O
+more	O
+likely	O
+to	O
+be	O
+ill	O
+or	O
+disabled	O
+than	O
+their	O
+richer	O
+compatriots	O
+,	O
+ranging	O
+from	O
+general	O
+disability	O
+in	O
+India	O
+,	O
+Bulgaria	O
+,	O
+and	O
+Ghana	O
+[	O
+21	O
+]	O
+;	O
+common	O
+mental	O
+disorders	O
+in	O
+Brazil	O
+,	O
+Chile	O
+,	O
+India	O
+,	O
+and	O
+Zimbabwe	O
+[	O
+22	O
+]	O
+;	O
+deafness	O
+in	O
+Brazil	O
+[	O
+23	O
+]	O
+;	O
+and	O
+tuberculosis	O
+in	O
+China	O
+[	O
+24	O
+]	O
+.	O
+
+There	O
+are	O
+also	O
+some	O
+exceptions	O
+such	O
+as	O
+a	O
+case	O
+-	O
+control	O
+study	O
+in	O
+Rwanda	O
+which	O
+failed	O
+to	O
+show	O
+an	O
+association	O
+between	O
+PCE	O
+and	O
+musculoskeletal	O
+impairment	O
+,	O
+perhaps	O
+because	O
+the	O
+population	O
+was	O
+almost	O
+universally	O
+poor	O
+[	O
+25	O
+]	O
+.	O
+
+Poverty	O
+may	O
+increase	O
+the	O
+incidence	O
+of	O
+disease	O
+,	O
+particularly	O
+preventable	O
+diseases	O
+such	O
+as	O
+tuberculosis	O
+.	O
+
+Poverty	O
+may	O
+also	O
+restrict	O
+access	O
+to	O
+appropriate	O
+health	O
+care	O
+and	O
+so	O
+prolong	O
+the	O
+duration	O
+of	O
+disease	O
+.	O
+
+A	O
+study	O
+in	O
+rural	O
+Tanzania	O
+showed	O
+that	O
+care	O
+-	O
+seeking	O
+behaviour	O
+for	O
+childhood	O
+illness	O
+is	O
+worse	O
+among	O
+poorer	O
+families	O
+than	O
+among	O
+the	O
+relatively	O
+rich	O
+families	O
+[	O
+26	O
+]	O
+.	O
+
+Another	O
+Tanzanian	O
+study	O
+found	O
+that	O
+people	B
+with	O
+higher	O
+levels	O
+of	O
+asset	O
+ownership	O
+were	O
+more	O
+likely	O
+to	O
+obtain	O
+antimalarials	O
+even	O
+though	O
+they	O
+were	O
+less	O
+likely	O
+to	O
+be	O
+parasitaemic	O
+[	O
+27	O
+]	O
+.	O
+
+With	O
+respect	O
+to	O
+cataract	O
+,	O
+there	O
+is	O
+little	O
+evidence	O
+that	O
+prevention	O
+is	O
+possible	O
+,	O
+and	O
+so	O
+the	O
+main	O
+pathway	O
+from	O
+poverty	O
+to	O
+blindness	O
+is	O
+likely	O
+to	O
+be	O
+through	O
+reduced	O
+access	O
+to	O
+cataract	O
+surgical	O
+services	O
+.	O
+
+High	O
+health	O
+care	O
+costs	O
+may	O
+also	O
+exacerbate	O
+poverty	O
+.	O
+
+A	O
+study	O
+in	O
+rural	O
+China	O
+showed	O
+that	O
+ill	O
+health	O
+increases	O
+medical	O
+expenditure	O
+significantly	O
+,	O
+which	O
+detracts	O
+from	O
+expenditure	O
+on	O
+food	O
+,	O
+education	O
+,	O
+investment	O
+in	O
+farming	O
+,	O
+and	O
+participation	O
+in	O
+social	O
+activities	O
+[	O
+28	O
+]	O
+.	O
+
+Inability	O
+to	O
+afford	O
+cataract	O
+surgery	O
+is	O
+cited	O
+as	O
+the	O
+major	O
+barrier	O
+to	O
+the	O
+uptake	O
+of	O
+surgery	O
+in	O
+the	O
+surveys	O
+conducted	O
+in	O
+Kenya	O
+,	O
+the	O
+Philippines	O
+,	O
+and	O
+Bangladesh	O
+[	O
+6	O
+-	O
+8	O
+]	O
+.	O
+
+This	O
+indicates	O
+that	O
+the	O
+cost	O
+of	O
+surgery	O
+is	O
+perceived	O
+as	O
+substantial	O
+by	O
+many	O
+households	O
+,	O
+notwithstanding	O
+the	O
+problems	O
+of	O
+assessing	O
+the	O
+complex	O
+issue	O
+of	O
+barriers	O
+in	O
+the	O
+absence	O
+of	O
+in	O
+-	O
+depth	O
+qualitative	O
+interviews	O
+.	O
+
+Consequently	O
+,	O
+there	O
+are	O
+lower	O
+rates	O
+of	O
+cataract	O
+surgery	O
+among	O
+the	O
+poor	O
+[	O
+3	O
+]	O
+.	O
+
+Poverty	O
+may	O
+also	O
+limit	O
+the	O
+employment	O
+opportunities	O
+of	O
+the	O
+person	B
+with	O
+disability	O
+or	O
+their	O
+household	O
+members	O
+.	O
+
+This	O
+pattern	O
+has	O
+been	O
+demonstrated	O
+for	O
+people	B
+with	O
+HIV	B
+in	O
+South	O
+Africa	O
+[	O
+29	O
+]	O
+,	O
+tuberculosis	O
+in	O
+China	O
+[	O
+24	O
+]	O
+,	O
+or	O
+disability	O
+in	O
+Sri	O
+Lanka	O
+[	O
+22	O
+]	O
+.	O
+
+An	O
+impact	O
+of	O
+blindness	O
+on	O
+reduced	O
+employment	O
+or	O
+income	O
+has	O
+been	O
+observed	O
+in	O
+Guinea	O
+[	O
+9	O
+]	O
+and	O
+India	O
+[	O
+4	O
+]	O
+.	O
+
+A	O
+belief	O
+that	O
+blindness	O
+reduces	O
+the	O
+employment	O
+opportunities	O
+of	O
+household	O
+members	O
+is	O
+widespread	O
+,	O
+but	O
+so	O
+far	O
+there	O
+is	O
+limited	O
+supportive	O
+evidence	O
+.	O
+
+There	O
+is	O
+a	O
+further	O
+complication	O
+to	O
+investigations	O
+of	O
+the	O
+relationship	O
+between	O
+cataract	O
+and	O
+poverty	O
+,	O
+as	O
+the	O
+individuals	O
+with	O
+cataract	O
+are	O
+likely	O
+to	O
+be	O
+elderly	O
+and	O
+facing	O
+multiple	O
+disabilities	O
+.	O
+
+Our	O
+study	O
+took	O
+account	O
+of	O
+the	O
+potential	O
+impact	O
+of	O
+multiple	O
+disabilities	O
+,	O
+as	O
+we	O
+adjusted	O
+for	O
+self	O
+-	O
+rated	O
+health	O
+,	O
+which	O
+is	O
+closely	O
+related	O
+to	O
+overall	O
+health	O
+,	O
+and	O
+this	O
+adjustment	O
+had	O
+no	O
+overall	O
+impact	O
+on	O
+our	O
+results	O
+[	O
+30	O
+]	O
+.	O
+
+Study	O
+Strengths	O
+
+This	O
+was	O
+a	O
+large	O
+population	O
+-	O
+based	O
+case	O
+-	O
+control	O
+study	O
+,	O
+conducted	O
+in	O
+three	O
+countries	O
+,	O
+allowing	O
+international	O
+comparisons	O
+.	O
+
+This	O
+was	O
+the	O
+first	O
+study	O
+,	O
+to	O
+our	O
+knowledge	O
+,	O
+to	O
+relate	O
+PCE	O
+to	O
+visual	O
+impairment	O
+.	O
+
+We	O
+also	O
+measured	O
+assets	O
+,	O
+which	O
+reflects	O
+long	O
+-	O
+term	O
+access	O
+to	O
+resources	O
+,	O
+and	O
+self	O
+-	O
+rated	O
+wealth	O
+.	O
+
+We	O
+used	O
+expenditure	O
+as	O
+a	O
+proxy	O
+for	O
+income	O
+,	O
+which	O
+has	O
+aided	O
+both	O
+academic	O
+and	O
+nonacademic	O
+investigations	O
+.	O
+
+As	O
+one	O
+example	O
+,	O
+the	O
+notorious	O
+Chicago	O
+gangster	O
+Al	O
+Capone	O
+managed	O
+to	O
+escape	O
+prosecution	O
+for	O
+smuggling	O
+,	O
+gambling	O
+,	O
+bootlegging	O
+,	O
+and	O
+murder	O
+for	O
+years	O
+,	O
+but	O
+was	O
+eventually	O
+convicted	O
+of	O
+tax	O
+evasion	O
+,	O
+because	O
+the	O
+jury	O
+was	O
+convinced	O
+that	O
+his	O
+exorbitant	O
+expenses	O
+on	O
+clothes	O
+,	O
+furnishing	O
+,	O
+foods	O
+,	O
+and	O
+gifts	O
+were	O
+inconsistent	O
+with	O
+his	O
+claim	O
+that	O
+he	O
+had	O
+no	O
+income	O
+.	O
+
+Expenditure	O
+often	O
+provides	O
+a	O
+better	O
+measure	O
+of	O
+poverty	O
+than	O
+income	O
+for	O
+a	O
+number	O
+of	O
+reasons	O
+.	O
+
+Income	O
+may	O
+be	O
+variable	O
+by	O
+season	O
+,	O
+whereas	O
+households	O
+attempt	O
+to	O
+smooth	O
+expenditure	O
+over	O
+the	O
+year	O
+.	O
+
+People	B
+are	O
+more	O
+comfortable	O
+sharing	O
+information	O
+about	O
+expenditure	O
+than	O
+income	O
+,	O
+and	O
+it	O
+may	O
+be	O
+a	O
+more	O
+meaningful	O
+measure	O
+than	O
+income	O
+in	O
+an	O
+agrarian	O
+society	O
+as	O
+it	O
+reflects	O
+what	O
+the	O
+household	O
+is	O
+able	O
+to	O
+command	O
+based	O
+on	O
+its	O
+current	O
+income	O
+,	O
+borrowing	O
+ability	O
+,	O
+or	O
+household	O
+savings	O
+[	O
+31	O
+]	O
+.	O
+
+PCE	O
+also	O
+has	O
+advantages	O
+over	O
+assets	O
+,	O
+as	O
+it	O
+may	O
+be	O
+more	O
+responsive	O
+to	O
+change	O
+,	O
+which	O
+will	O
+be	O
+important	O
+for	O
+the	O
+follow	O
+-	O
+up	O
+analyses	O
+of	O
+the	O
+study	O
+participants	B
+after	O
+they	O
+have	O
+undergone	O
+cataract	O
+surgery	O
+.	O
+
+Study	O
+Limitations	O
+
+There	O
+are	O
+a	O
+number	O
+of	O
+limitations	O
+relating	O
+to	O
+the	O
+measurement	O
+of	O
+poverty	O
+in	O
+this	O
+study	O
+.	O
+
+Our	O
+analyses	O
+focus	O
+on	O
+monetary	O
+indicators	O
+of	O
+poverty	O
+,	O
+while	O
+we	O
+acknowledge	O
+that	O
+health	O
+,	O
+education	O
+,	O
+and	O
+housing	O
+are	O
+also	O
+important	O
+.	O
+
+We	O
+concede	O
+that	O
+it	O
+is	O
+difficult	O
+to	O
+measure	O
+expenditure	O
+accurately	O
+[	O
+32	O
+,	O
+33	O
+]	O
+,	O
+but	O
+this	O
+also	O
+true	O
+for	O
+the	O
+measurement	O
+of	O
+diet	O
+and	O
+other	O
+variables	O
+,	O
+which	O
+is	O
+standard	O
+practise	O
+in	O
+many	O
+epidemiological	O
+studies	O
+.	O
+
+Furthermore	O
+,	O
+a	O
+large	O
+number	O
+of	O
+items	O
+were	O
+included	O
+in	O
+our	O
+measure	O
+of	O
+expenditure	O
+so	O
+that	O
+the	O
+measure	O
+was	O
+comprehensive	O
+[	O
+33	O
+]	O
+.	O
+
+Expenditure	O
+data	O
+were	O
+not	O
+validated	O
+through	O
+diaries	O
+or	O
+other	O
+means	O
+,	O
+although	O
+assets	O
+and	O
+self	O
+-	O
+rated	O
+wealth	O
+correlated	O
+highly	O
+with	O
+PCE	O
+.	O
+
+Other	O
+recent	O
+estimates	O
+of	O
+expenditure	O
+are	O
+not	O
+available	O
+from	O
+surveys	O
+conducted	O
+in	O
+these	O
+countries	O
+to	O
+allow	O
+comparison	O
+.	O
+
+The	O
+per	O
+capita	O
+estimates	O
+of	O
+monthly	O
+gross	O
+national	O
+income	O
+from	O
+the	O
+World	O
+Development	O
+Indicators	O
+database	O
+show	O
+somewhat	O
+higher	O
+estimates	O
+in	O
+Kenya	O
+(	O
+US	O
+$	O
+48	O
+)	O
+and	O
+Bangladesh	O
+(	O
+US	O
+$	O
+40	O
+)	O
+than	O
+our	O
+PCE	O
+derived	O
+estimates	O
+,	O
+and	O
+far	O
+higher	O
+estimates	O
+for	O
+the	O
+Philippines	O
+(	O
+US	O
+$	O
+108	O
+)	O
+.	O
+
+This	O
+discrepancy	O
+may	O
+be	O
+reasonable	O
+,	O
+as	O
+the	O
+World	O
+Development	O
+Indicators	O
+reflect	O
+national	O
+averages	O
+,	O
+while	O
+we	O
+sampled	O
+the	O
+households	O
+with	O
+elderly	O
+people	B
+in	O
+poor	O
+regions	O
+of	O
+the	O
+country	O
+,	O
+many	O
+of	O
+whom	O
+were	O
+visually	O
+impaired	O
+from	O
+cataract	O
+.	O
+
+PCE	O
+was	O
+calculated	O
+simply	O
+by	O
+dividing	O
+the	O
+total	O
+household	O
+expenditure	O
+by	O
+the	O
+number	O
+of	O
+household	O
+members	O
+,	O
+without	O
+inclusion	O
+of	O
+economies	O
+of	O
+scale	O
+or	O
+equivalence	O
+scales	O
+.	O
+
+There	O
+is	O
+no	O
+widely	O
+accepted	O
+alternative	O
+to	O
+the	O
+simple	O
+equal	O
+-	O
+sharing	O
+convention	O
+,	O
+and	O
+the	O
+majority	O
+of	O
+expenditure	O
+was	O
+on	O
+food	O
+which	O
+does	O
+not	O
+allow	O
+for	O
+economies	O
+of	O
+scale	O
+.	O
+
+Furthermore	O
+,	O
+there	O
+were	O
+slightly	O
+fewer	O
+people	B
+of	O
+working	O
+age	O
+in	O
+the	O
+control	O
+households	O
+in	O
+Kenya	O
+and	O
+the	O
+Philippines	O
+,	O
+so	O
+adjustment	O
+for	O
+equivalence	O
+scores	O
+would	O
+be	O
+unlikely	O
+to	O
+explain	O
+the	O
+higher	O
+poverty	O
+among	O
+cases	O
+.	O
+
+The	O
+case	O
+and	O
+control	O
+households	O
+were	O
+of	O
+similar	O
+sizes	O
+in	O
+the	O
+three	O
+settings	O
+,	O
+so	O
+economies	O
+of	O
+scales	O
+are	O
+unlikely	O
+to	O
+have	O
+explained	O
+the	O
+differences	O
+.	O
+
+There	O
+were	O
+a	O
+number	O
+of	O
+limitations	O
+relating	O
+to	O
+study	O
+design	O
+.	O
+
+Unfortunately	O
+,	O
+we	O
+did	O
+not	O
+record	O
+the	O
+exact	O
+numbers	O
+of	O
+cases	O
+and	O
+controls	O
+who	O
+refused	O
+to	O
+participate	O
+or	O
+were	O
+unable	O
+to	O
+communicate	O
+(	O
+believed	O
+to	O
+be	O
+fewer	O
+than	O
+five	O
+in	O
+each	O
+country	O
+)	O
+,	O
+so	O
+the	O
+response	O
+rate	O
+is	O
+unknown	O
+,	O
+but	O
+was	O
+believed	O
+to	O
+be	O
+high	O
+.	O
+
+A	O
+variety	O
+of	O
+methods	O
+were	O
+used	O
+for	O
+case	O
+recruitment	O
+,	O
+as	O
+we	O
+were	O
+not	O
+able	O
+to	O
+obtain	O
+enough	O
+cases	O
+through	O
+the	O
+survey	O
+alone	O
+.	O
+
+However	O
+,	O
+cases	O
+recruited	O
+through	O
+the	O
+population	O
+-	O
+based	O
+survey	O
+and	O
+through	O
+case	O
+detection	O
+had	O
+similar	O
+poverty	O
+characteristics	O
+.	O
+
+Conclusions	O
+
+Our	O
+data	O
+show	O
+that	O
+people	B
+with	O
+visual	O
+impairment	O
+due	O
+to	O
+cataract	O
+were	O
+poorer	O
+than	O
+controls	O
+in	O
+three	O
+low	O
+income	O
+countries	O
+,	O
+Bangladesh	O
+,	O
+Kenya	O
+,	O
+and	O
+the	O
+Philippines	O
+.	O
+
+The	O
+Millennium	O
+Development	O
+Goals	O
+are	O
+committed	O
+to	O
+the	O
+eradication	O
+of	O
+extreme	O
+poverty	O
+and	O
+provision	O
+of	O
+health	O
+care	O
+to	O
+poor	O
+people	B
+.	O
+
+This	O
+study	O
+confirms	O
+an	O
+association	O
+between	O
+poverty	O
+and	O
+blindness	O
+and	O
+highlights	O
+the	O
+need	O
+for	O
+increased	O
+provision	O
+of	O
+cataract	O
+surgery	O
+to	O
+poor	O
+people	B
+,	O
+particularly	O
+since	O
+cataract	O
+surgery	O
+is	O
+a	O
+highly	O
+cost	O
+-	O
+effective	O
+intervention	O
+in	O
+these	O
+settings	O
+[	O
+34	O
+]	O
+.	O
+
+Human	B
+genetic	O
+selection	O
+on	O
+the	O
+MTHFR	O
+677C	O
+>	O
+T	O
+polymorphism	O
+
+Abstract	O
+
+Background	O
+
+The	O
+prevalence	O
+of	O
+genotypes	O
+of	O
+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
+for	O
+the	O
+MTHFR	O
+gene	O
+varies	O
+among	O
+humans	B
+.	O
+
+In	O
+previous	O
+studies	O
+,	O
+we	O
+found	O
+changes	O
+in	O
+the	O
+genotypic	O
+frequencies	O
+of	O
+this	O
+polymorphism	O
+in	O
+populations	O
+of	O
+different	O
+ages	O
+,	O
+suggesting	O
+that	O
+this	O
+could	O
+be	O
+caused	O
+by	O
+an	O
+increase	O
+in	O
+the	O
+intake	O
+of	O
+folate	O
+and	O
+multivitamins	O
+by	O
+women	B
+during	O
+the	O
+periconceptional	O
+period	O
+.	O
+
+The	O
+aim	O
+was	O
+to	O
+analyze	O
+changes	O
+in	O
+the	O
+allelic	O
+frequencies	O
+of	O
+this	O
+polymorphism	O
+in	O
+a	O
+Spanish	O
+population	O
+,	O
+including	O
+samples	O
+from	O
+spontaneous	O
+abortions	O
+(	O
+SA	O
+)	O
+.	O
+
+Methods	O
+
+A	O
+total	O
+of	O
+1305	O
+subjects	O
+born	O
+in	O
+the	O
+20th	O
+century	O
+were	O
+genotyped	O
+for	O
+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
+using	O
+allele	O
+specific	O
+real	O
+-	O
+time	O
+PCR	O
+with	O
+Taqman	O
+(	O
+R	O
+)	O
+probes	O
+.	O
+
+A	O
+section	O
+of	O
+our	O
+population	O
+(	O
+n	O
+=	O
+276	O
+)	O
+born	O
+in	O
+1980	O
+-	O
+1989	O
+was	O
+compared	O
+with	O
+fetal	O
+samples	O
+(	O
+n	O
+=	O
+344	O
+)	O
+from	O
+SA	O
+of	O
+unknown	O
+etiology	O
+from	O
+the	O
+same	O
+period	O
+.	O
+
+Results	O
+
+An	O
+increase	O
+in	O
+the	O
+frequency	O
+of	O
+the	O
+T	O
+allele	O
+(	O
+0	O
+.	O
+38	O
+vs	O
+0	O
+.	O
+47	O
+;	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+of	O
+the	O
+TT	O
+genotype	O
+(	O
+0	O
+.	O
+14	O
+vs	O
+0	O
+.	O
+24	O
+;	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+in	O
+subjects	O
+born	O
+in	O
+the	O
+last	O
+quarter	O
+of	O
+the	O
+century	O
+was	O
+observed	O
+.	O
+
+In	O
+the	O
+1980	O
+-	O
+1989	O
+period	O
+,	O
+the	O
+results	O
+show	O
+that	O
+the	O
+frequency	O
+of	O
+the	O
+wild	O
+type	O
+genotype	O
+(	O
+CC	O
+)	O
+is	O
+about	O
+tenfold	O
+lower	O
+in	O
+the	O
+SA	O
+samples	O
+than	O
+in	O
+the	O
+controls	O
+(	O
+0	O
+.	O
+03	O
+vs	O
+0	O
+.	O
+33	O
+;	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+and	O
+that	O
+the	O
+frequency	O
+of	O
+the	O
+TT	O
+genotype	O
+increases	O
+in	O
+the	O
+controls	O
+(	O
+0	O
+.	O
+19	O
+to	O
+0	O
+.	O
+27	O
+)	O
+and	O
+in	O
+the	O
+SA	O
+samples	O
+(	O
+0	O
+.	O
+20	O
+to	O
+0	O
+.	O
+33	O
+(	O
+p	O
+<	O
+0	O
+.	O
+01	O
+)	O
+)	O
+;	O
+r	O
+=	O
+0	O
+.	O
+98	O
+.	O
+
+Conclusion	O
+
+Selection	O
+in	O
+favor	O
+of	O
+the	O
+T	O
+allele	O
+has	O
+been	O
+detected	O
+.	O
+
+This	O
+selection	O
+could	O
+be	O
+due	O
+to	O
+the	O
+increased	O
+fetal	O
+viability	O
+in	O
+early	O
+stages	O
+of	O
+embryonic	O
+development	O
+,	O
+as	O
+is	O
+deduced	O
+by	O
+the	O
+increase	O
+of	O
+mutants	O
+in	O
+both	O
+living	O
+and	O
+SA	O
+populations	O
+.	O
+
+Background	O
+
+The	O
+methylenetetrahydrof	O
+reductase	O
+enzyme	O
+(	O
+MTHFR	O
+)	O
+catalyzes	O
+a	O
+reaction	O
+that	O
+produces	O
+5	O
+-	O
+methyltetrahydrofola	O
+(	O
+5	O
+-	O
+methylTHF	O
+)	O
+,	O
+the	O
+methyl	O
+donor	O
+for	O
+homocysteine	O
+in	O
+the	O
+synthesis	O
+of	O
+methionine	O
+.	O
+
+The	O
+677C	O
+>	O
+T	O
+mutation	O
+of	O
+the	O
+MTHFR	O
+gene	O
+has	O
+been	O
+associated	O
+with	O
+a	O
+thermolabile	O
+enzyme	O
+with	O
+decreased	O
+activity	O
+that	O
+may	O
+cause	O
+an	O
+increase	O
+in	O
+plasma	O
+homocysteine	O
+concentrations	O
+[	O
+1	O
+]	O
+when	O
+folate	O
+status	O
+is	O
+poor	O
+.	O
+
+This	O
+polymorphism	O
+is	O
+one	O
+of	O
+the	O
+most	O
+widely	O
+studied	O
+clinically	O
+relevant	O
+polymorphisms	O
+in	O
+humans	B
+,	O
+as	O
+it	O
+is	O
+related	O
+to	O
+cardiovascular	O
+disease	O
+[	O
+2	O
+]	O
+and	O
+neural	O
+tube	O
+defects	O
+(	O
+NTD	O
+;	O
+601634	O
+)	O
+[	O
+3	O
+]	O
+.	O
+
+A	O
+large	O
+number	O
+of	O
+studies	O
+have	O
+provided	O
+a	O
+broad	O
+overview	O
+of	O
+the	O
+prevalence	O
+of	O
+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
+in	O
+different	O
+human	B
+populations	O
+,	O
+showing	O
+that	O
+the	O
+distribution	O
+of	O
+frequencies	O
+is	O
+diverse	O
+[	O
+4	O
+]	O
+.	O
+
+These	O
+differences	O
+have	O
+been	O
+also	O
+observed	O
+between	O
+groups	O
+of	O
+different	O
+ages	O
+in	O
+the	O
+same	O
+Spanish	O
+population	O
+(	O
+older	O
+and	O
+younger	O
+than	O
+24	O
+years	O
+)	O
+[	O
+5	O
+]	O
+and	O
+in	O
+a	O
+Swiss	O
+population	O
+(	O
+older	O
+and	O
+younger	O
+than	O
+60	O
+years	O
+)	O
+[	O
+6	O
+]	O
+,	O
+as	O
+well	O
+as	O
+in	O
+a	O
+Japanese	O
+population	O
+[	O
+7	O
+]	O
+.	O
+
+In	O
+some	O
+populations	O
+,	O
+such	O
+the	O
+Toscanians	O
+in	O
+Italy	O
+[	O
+8	O
+]	O
+and	O
+Mexicans	O
+[	O
+9	O
+]	O
+,	O
+the	O
+homozygous	O
+mutated	O
+genotype	O
+(	O
+TT	O
+)	O
+has	O
+reached	O
+frequencies	O
+greater	O
+than	O
+30	O
+%	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+in	O
+Africans	O
+the	O
+frequency	O
+of	O
+the	O
+TT	O
+genotype	O
+is	O
+very	O
+low	O
+(	O
+less	O
+than	O
+1	O
+%	O
+)	O
+[	O
+10	O
+,	O
+11	O
+]	O
+,	O
+but	O
+,	O
+in	O
+African	O
+-	O
+Americans	O
+,	O
+it	O
+has	O
+already	O
+reached	O
+2	O
+%	O
+[	O
+12	O
+]	O
+.	O
+
+Studies	O
+based	O
+on	O
+the	O
+distribution	O
+of	O
+genotypic	O
+and	O
+allelic	O
+frequencies	O
+of	O
+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
+and	O
+the	O
+1298A	O
+>	O
+C	O
+polymorphism	O
+in	O
+the	O
+MTHFR	O
+gene	O
+in	O
+Israeli	O
+,	O
+Japanese	O
+and	O
+Ghanaian	O
+Africans	O
+populations	O
+[	O
+13	O
+]	O
+concluded	O
+that	O
+the	O
+677T	O
+mutation	O
+in	O
+the	O
+MTHFR	O
+gene	O
+emerged	O
+as	O
+a	O
+founder	O
+haplotype	O
+with	O
+some	O
+selective	O
+advantage	O
+.	O
+
+Recently	O
+,	O
+preliminary	O
+evidence	O
+of	O
+genetic	O
+selection	O
+of	O
+this	O
+polymorphism	O
+related	O
+to	O
+folate	O
+intake	O
+has	O
+been	O
+reported	O
+[	O
+14	O
+]	O
+.	O
+
+The	O
+aim	O
+of	O
+the	O
+present	O
+study	O
+is	O
+to	O
+analyze	O
+the	O
+changes	O
+in	O
+frequencies	O
+of	O
+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
+during	O
+the	O
+20th	O
+century	O
+and	O
+particularly	O
+the	O
+evolution	O
+of	O
+the	O
+frequencies	O
+during	O
+the	O
+decade	O
+of	O
+1980	O
+-	O
+1989	O
+,	O
+by	O
+comparing	O
+the	O
+genotype	O
+frequencies	O
+between	O
+living	O
+subjects	O
+born	O
+in	O
+this	O
+period	O
+versus	O
+samples	O
+of	O
+spontaneous	O
+abortions	O
+(	O
+SA	O
+)	O
+that	O
+occurred	O
+during	O
+in	O
+the	O
+same	O
+time	O
+period	O
+.	O
+
+Methods	O
+
+Subjects	O
+
+This	O
+study	O
+was	O
+approved	O
+by	O
+the	O
+Ethics	O
+Committee	O
+at	O
+the	O
+University	O
+Hospital	O
+"	O
+Virgen	O
+de	O
+la	O
+Victoria	O
+"	O
+(	O
+M	O
+a	O
+laga	O
+)	O
+.	O
+
+One	O
+of	O
+the	O
+study	O
+groups	O
+consisted	O
+of	O
+344	O
+fetal	O
+tissue	O
+samples	O
+from	O
+SA	O
+,	O
+obtained	O
+from	O
+the	O
+Department	O
+of	O
+Pathology	O
+of	O
+the	O
+University	O
+Hospital	O
+Carlos	O
+Haya	O
+(	O
+M	O
+a	O
+laga	O
+)	O
+.	O
+
+These	O
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+were	O
+selected	O
+after	O
+checking	O
+the	O
+clinical	O
+history	O
+and	O
+by	O
+the	O
+inclusion	O
+criteria	O
+of	O
+containing	O
+histologically	O
+confirmed	O
+fetal	O
+tissue	O
+collected	O
+in	O
+the	O
+1980s	O
+from	O
+SA	O
+at	O
+less	O
+than	O
+3	O
+months	O
+(	O
+11	O
++	O
+/	O
+-	O
+1	O
+.	O
+70	O
+week	O
+)	O
+and	O
+of	O
+unknown	O
+etiology	O
+.	O
+
+These	O
+fetal	O
+samples	O
+were	O
+compared	O
+with	O
+a	O
+control	O
+population	O
+of	O
+276	O
+subjects	O
+born	O
+in	O
+the	O
+1980s	O
+with	O
+an	O
+average	O
+age	O
+of	O
+22	O
++	O
+/	O
+-	O
+4	O
+.	O
+58	O
+.	O
+
+Another	O
+population	O
+of	O
+subjects	O
+born	O
+in	O
+the	O
+south	O
+of	O
+Spain	O
+in	O
+the	O
+20th	O
+century	O
+were	O
+genotyped	O
+(	O
+1305	O
+subjects	O
+,	O
+697	O
+women	B
+and	O
+608	O
+men	B
+)	O
+and	O
+divided	O
+into	O
+four	O
+groups	O
+according	O
+to	O
+birth	O
+date	O
+:	O
+1900	O
+to	O
+1925	O
+(	O
+n	O
+=	O
+206	O
+)	O
+;	O
+1926	O
+to	O
+1950	O
+(	O
+n	O
+=	O
+320	O
+)	O
+,	O
+1951	O
+to	O
+1975	O
+(	O
+n	O
+=	O
+408	O
+)	O
+,	O
+1976	O
+to	O
+2000	O
+(	O
+n	O
+=	O
+371	O
+)	O
+.	O
+
+Individuals	O
+were	O
+selected	O
+randomly	O
+from	O
+different	O
+areas	O
+of	O
+the	O
+province	O
+of	O
+Malaga	O
+,	O
+in	O
+southern	O
+Spain	O
+,	O
+and	O
+from	O
+different	O
+social	O
+statuses	O
+to	O
+avoid	O
+a	O
+selection	O
+bias	O
+.	O
+
+All	O
+the	O
+selected	O
+individuals	O
+were	O
+Caucasian	O
+and	O
+residents	O
+of	O
+the	O
+study	O
+area	O
+.	O
+
+The	O
+parents	O
+of	O
+all	O
+subjects	O
+included	O
+in	O
+the	O
+study	O
+were	O
+also	O
+Caucasian	O
+and	O
+born	O
+in	O
+Spain	O
+.	O
+
+The	O
+possibility	O
+of	O
+a	O
+founder	O
+effect	O
+or	O
+genetic	O
+drift	O
+was	O
+investigated	O
+and	O
+rejected	O
+.	O
+
+All	O
+the	O
+selected	O
+individuals	O
+were	O
+also	O
+genotyped	O
+for	O
+an	O
+insertion	O
+/	O
+deletion	O
+polymorphism	O
+in	O
+the	O
+angiotensin	O
+converting	O
+enzyme	O
+(	O
+ACE	O
+)	O
+gene	O
+and	O
+/	O
+or	O
+the	O
+2756A	O
+>	O
+G	O
+polymorphism	O
+in	O
+the	O
+methionine	O
+synthase	O
+gene	O
+(	O
+MTR	O
+)	O
+,	O
+in	O
+order	O
+to	O
+determine	O
+whether	O
+or	O
+not	O
+our	O
+adult	O
+and	O
+young	O
+populations	O
+were	O
+genetically	O
+homogeneous	O
+.	O
+
+No	O
+significant	O
+differences	O
+were	O
+observed	O
+in	O
+allelic	O
+or	O
+genotypic	O
+frequencies	O
+for	O
+these	O
+genes	O
+between	O
+the	O
+different	O
+groups	O
+.	O
+
+The	O
+population	O
+studied	O
+was	O
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+selected	O
+according	O
+to	O
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+.	O
+
+Subjects	O
+0	O
+-	O
+12	O
+years	O
+old	O
+were	O
+selected	O
+from	O
+dried	O
+blood	O
+spots	O
+from	O
+neonatal	O
+screening	O
+papers	O
+;	O
+subjects	O
+10	O
+-	O
+24	O
+years	O
+old	O
+were	O
+recruited	O
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+students	O
+in	O
+primary	O
+and	O
+secondary	O
+schools	O
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+in	O
+university	O
+;	O
+subjects	O
+25	O
+-	O
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+and	O
+>	O
+51	O
+years	O
+old	O
+were	O
+recruited	O
+using	O
+their	O
+Andalusia	O
+Health	O
+Service	O
+identity	O
+cards	O
+.	O
+
+After	O
+approval	O
+by	O
+the	O
+University	O
+Hospital	O
+Ethical	O
+Committee	O
+,	O
+all	O
+the	O
+subjects	O
+were	O
+contacted	O
+,	O
+and	O
+,	O
+from	O
+those	O
+whose	O
+written	O
+consent	O
+was	O
+obtained	O
+,	O
+10	O
+ml	O
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+blood	O
+was	O
+taken	O
+.	O
+
+The	O
+investigation	O
+in	O
+this	O
+study	O
+conforms	O
+to	O
+the	O
+principles	O
+outlined	O
+in	O
+the	O
+Declaration	O
+of	O
+Helsinki	O
+.	O
+
+Genetic	O
+analysis	O
+
+The	O
+fetal	O
+samples	O
+were	O
+extracted	O
+from	O
+the	O
+archived	O
+formalin	O
+-	O
+fixed	O
+,	O
+paraffin	O
+-	O
+embedded	O
+tissue	O
+sections	O
+.	O
+
+Genomic	O
+DNA	O
+was	O
+extracted	O
+from	O
+fetal	O
+tissue	O
+using	O
+the	O
+method	O
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+Coombs	O
+et	O
+al	O
+.	O
+
+(	O
+1999	O
+)	O
+[	O
+15	O
+]	O
+.	O
+
+Genomic	O
+DNA	O
+of	O
+the	O
+second	O
+and	O
+third	O
+groups	O
+was	O
+extracted	O
+from	O
+peripheral	O
+leukocytes	O
+using	O
+the	O
+AquaPure	O
+Genomic	O
+DNA	O
+Blood	O
+Kit	O
+(	O
+Bio	O
+-	O
+Rad	O
+)	O
+.	O
+
+Genotyping	O
+was	O
+performed	O
+using	O
+Real	O
+Time	O
+PCR	O
+with	O
+allele	O
+specific	O
+Taqman	O
+(	O
+R	O
+)	O
+probes	O
+and	O
+primers	O
+described	O
+by	O
+Ulvik	O
+et	O
+al	O
+.	O
+
+(	O
+2001	O
+)	O
+[	O
+16	O
+]	O
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+protocol	O
+for	O
+45	O
+cycles	O
+:	O
+10	O
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+-	O
+94	O
+degrees	O
+C	O
+,	O
+40	O
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+-	O
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+C	O
+,	O
+15	O
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+-	O
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+C	O
+.	O
+
+The	O
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+mix	O
+(	O
+25	O
+mu	O
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+volume	O
+)	O
+consisted	O
+of	O
+5	O
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+DNA	O
+,	O
+0	O
+.	O
+5	O
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+of	O
+sense	O
+primer	O
+,	O
+0	O
+.	O
+62	O
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+anti	O
+-	O
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+primer	O
+,	O
+0	O
+.	O
+85	O
+mu	O
+l	O
+Taqman	O
+(	O
+R	O
+)	O
+probe	O
+FAM	O
+,	O
+0	O
+.	O
+43	O
+mu	O
+l	O
+Taqman	O
+(	O
+R	O
+)	O
+probe	O
+TET	O
+,	O
+20	O
+mu	O
+l	O
+PCR	O
+-	O
+buffer	O
+iQ	O
+-	O
+SupermixTM	O
+(	O
+Bio	O
+-	O
+Rad	O
+)	O
+(	O
+containing	O
+100	O
+mM	O
+KCl	O
+,	O
+40	O
+mM	O
+Tris	O
+-	O
+HCl	O
+,	O
+(	O
+pH	O
+8	O
+.	O
+4	O
+)	O
+1	O
+.	O
+6	O
+mM	O
+dNTP	O
+(	O
+dATP	O
+,	O
+dCTP	O
+,	O
+dGTP	O
+and	O
+dTTP	O
+)	O
+,	O
+iTaq	O
+(	O
+R	O
+)	O
+polymerase	O
+(	O
+50	O
+units	O
+/	O
+mL	O
+)	O
+and	O
+6	O
+mM	O
+MgCl2	O
+)	O
+and	O
+17	O
+.	O
+75	O
+mu	O
+l	O
+H2O	O
+.	O
+
+Statistical	O
+and	O
+mathematical	O
+analysis	O
+
+All	O
+samples	O
+were	O
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+,	O
+and	O
+the	O
+allelic	O
+and	O
+genotypic	O
+frequencies	O
+were	O
+compared	O
+.	O
+
+Differences	O
+were	O
+analyzed	O
+statistically	O
+using	O
+the	O
+chi	O
+-	O
+square	O
+test	O
+or	O
+Fisher	O
+'	O
+s	O
+exact	O
+test	O
+.	O
+
+Correlations	O
+are	O
+expressed	O
+using	O
+Pearson	O
+'	O
+s	O
+coefficient	O
+(	O
+r	O
+)	O
+.	O
+
+Compliance	O
+of	O
+genotype	O
+distributions	O
+with	O
+Hardy	O
+-	O
+Weinberg	O
+(	O
+HW	O
+)	O
+equilibrium	O
+was	O
+evaluated	O
+by	O
+chi	O
+-	O
+square	O
+analysis	O
+.	O
+
+For	O
+all	O
+tests	O
+,	O
+a	O
+p	O
+-	O
+value	O
+<	O
+0	O
+.	O
+05	O
+was	O
+considered	O
+to	O
+be	O
+statistically	O
+significant	O
+.	O
+
+Values	O
+are	O
+expressed	O
+as	O
+the	O
+mean	O
++	O
+/	O
+-	O
+SD	O
+.	O
+
+The	O
+genetic	O
+selection	O
+model	O
+was	O
+calculated	O
+for	O
+the	O
+evolution	O
+of	O
+the	O
+677C	O
+>	O
+T	O
+genotypes	O
+.	O
+
+The	O
+genetic	O
+selection	O
+could	O
+be	O
+classified	O
+as	O
+codominant	O
+or	O
+incompletely	O
+dominant	O
+and	O
+directional	O
+with	O
+the	O
+heterozygous	O
+genotype	O
+having	O
+an	O
+intermediate	O
+fitness	O
+.	O
+
+For	O
+this	O
+kind	O
+of	O
+selection	O
+,	O
+the	O
+most	O
+appropriate	O
+mathematical	O
+model	O
+is	O
+dq	O
+=	O
+[	O
+spq	O
+(	O
+2hp	O
++	O
+q	O
+-	O
+h	O
+)	O
+]	O
+/	O
+[	O
+p2	O
++	O
+2pq	O
+(	O
+1	O
+-	O
+hs	O
+)	O
++	O
+q2	O
+x	O
+(	O
+1	O
+-	O
+s	O
+)	O
+]	O
+,	O
+where	O
+dq	O
+is	O
+the	O
+change	O
+of	O
+frequency	O
+of	O
+the	O
+allele	O
+with	O
+lower	O
+fitness	O
+,	O
+s	O
+is	O
+the	O
+fraction	O
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+that	O
+genotype	O
+lost	O
+to	O
+selection	O
+,	O
+h	O
+is	O
+the	O
+degree	O
+of	O
+dominance	O
+(	O
+between	O
+0	O
+,	O
+for	O
+no	O
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+1	O
+,	O
+for	O
+complete	O
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+)	O
+,	O
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+with	O
+higher	O
+fitness	O
+.	O
+
+Results	O
+
+We	O
+analyzed	O
+the	O
+genotype	O
+frequencies	O
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+the	O
+677C	O
+>	O
+T	O
+polymorphism	O
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+a	O
+population	O
+born	O
+during	O
+the	O
+20th	O
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+.	O
+
+A	O
+total	O
+of	O
+1305	O
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+divided	O
+into	O
+four	O
+groups	O
+of	O
+25	O
+years	O
+according	O
+to	O
+birth	O
+date	O
+.	O
+
+The	O
+genotype	O
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+(	O
+p	O
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+0	O
+.	O
+001	O
+)	O
+in	O
+the	O
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+in	O
+the	O
+last	O
+quarter	O
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+the	O
+20th	O
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+(	O
+1976	O
+-	O
+2000	O
+)	O
+,	O
+when	O
+compared	O
+to	O
+any	O
+of	O
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+other	O
+groups	O
+.	O
+
+The	O
+changes	O
+show	O
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+the	O
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+genotype	O
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+genotype	O
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+last	O
+25	O
+years	O
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+.	O
+
+(	O
+Table	O
+1	O
+)	O
+
+Considering	O
+that	O
+each	O
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+,	O
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+not	O
+change	O
+during	O
+the	O
+first	O
+75	O
+years	O
+of	O
+the	O
+century	O
+(	O
+HW	O
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+)	O
+.	O
+
+However	O
+,	O
+we	O
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+that	O
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+and	O
+genotypic	O
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+for	O
+the	O
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+>	O
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+last	O
+quarter	O
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+to	O
+the	O
+previous	O
+generation	O
+(	O
+1951	O
+-	O
+1975	O
+)	O
+.	O
+
+The	O
+genotype	O
+frequencies	O
+in	O
+the	O
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+quarter	O
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+the	O
+century	O
+are	O
+not	O
+the	O
+expected	O
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+a	O
+HW	O
+calculation	O
+using	O
+the	O
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+frequencies	O
+of	O
+the	O
+previous	O
+generation	O
+.	O
+
+This	O
+could	O
+be	O
+described	O
+as	O
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+consequence	O
+of	O
+genetic	O
+selection	O
+found	O
+in	O
+this	O
+population	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+other	O
+causes	O
+.	O
+
+Applying	O
+the	O
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+above	O
+to	O
+our	O
+population	O
+,	O
+the	O
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+fitness	O
+(	O
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+)	O
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+0	O
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+5	O
+,	O
+and	O
+it	O
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+that	O
+both	O
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+a	O
+frequency	O
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+50	O
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+the	O
+next	O
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+be	O
+at	O
+90	O
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+(	O
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+)	O
+.	O
+
+Another	O
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+which	O
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+of	O
+about	O
+50	O
+%	O
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+the	O
+next	O
+generation	O
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+that	O
+they	O
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+this	O
+stability	O
+while	O
+conditions	O
+remain	O
+unchanged	O
+.	O
+
+(	O
+Figure	O
+1B	O
+)	O
+
+The	O
+comparison	O
+of	O
+the	O
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+group	O
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+fetal	O
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+SA	O
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+occurred	O
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+-	O
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+(	O
+p	O
+<	O
+0	O
+.	O
+001	O
+)	O
+.	O
+
+CC	O
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+were	O
+almost	O
+absent	O
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+abortion	O
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+to	O
+living	O
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+(	O
+0	O
+.	O
+03	O
+vs	O
+0	O
+.	O
+33	O
+)	O
+,	O
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+the	O
+same	O
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+
+When	O
+3	O
+-	O
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+,	O
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+(	O
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+0	O
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+0	O
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+01	O
+)	O
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+
+Allele	O
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+(	O
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+0	O
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+)	O
+.	O
+
+Controls	O
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+.	O
+
+(	O
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+)	O
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+The	O
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+-	O
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+r	O
+=	O
+0	O
+.	O
+98	O
+(	O
+p	O
+=	O
+0	O
+.	O
+11	O
+)	O
+.	O
+
+Discussion	O
+
+Different	O
+reports	O
+show	O
+that	O
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+the	O
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+.	O
+
+Evidence	O
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+this	O
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+can	O
+be	O
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+many	O
+reports	O
+:	O
+frequency	O
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+that	O
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+very	O
+close	O
+,	O
+even	O
+in	O
+the	O
+same	O
+country	O
+[	O
+8	O
+]	O
+;	O
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+the	O
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+race	O
+or	O
+ethnic	O
+group	O
+such	O
+as	O
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+[	O
+10	O
+,	O
+11	O
+]	O
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+African	O
+-	O
+Americans	O
+[	O
+12	O
+]	O
+;	O
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+the	O
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+such	O
+as	O
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+[	O
+9	O
+]	O
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+[	O
+13	O
+]	O
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+Spain	O
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+,	O
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+[	O
+6	O
+]	O
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+[	O
+7	O
+]	O
+.	O
+
+There	O
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+this	O
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+,	O
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+as	O
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+status	O
+.	O
+
+Dependence	O
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+,	O
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+.	O
+
+Definitely	O
+,	O
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+,	O
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+certain	O
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+
+In	O
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+,	O
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+fetuses	O
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+.	O
+
+This	O
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+mid	O
+-	O
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+[	O
+5	O
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+in	O
+Spain	O
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+18	O
+,	O
+19	O
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+.	O
+
+In	O
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+,	O
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+new	O
+study	O
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+the	O
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+>	O
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+>	O
+C	O
+polymorphisms	O
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+age	O
+groups	O
+.	O
+
+Total	O
+homocysteine	O
+(	O
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+)	O
+levels	O
+in	O
+plasma	O
+were	O
+also	O
+analyzed	O
+according	O
+to	O
+the	O
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+interactions	O
+[	O
+20	O
+]	O
+.	O
+
+That	O
+study	O
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+of	O
+non	O
+-	O
+linkage	O
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+.	O
+
+Recently	O
+,	O
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+,	O
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+,	O
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+abortion	O
+[	O
+21	O
+]	O
+.	O
+
+In	O
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+present	O
+study	O
+,	O
+significant	O
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+allelic	O
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+genotypic	O
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+,	O
+as	O
+is	O
+Hardy	O
+-	O
+Weinberg	O
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+,	O
+at	O
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+677C	O
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+.	O
+
+We	O
+hypothesize	O
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+dynamic	O
+process	O
+of	O
+genetic	O
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+favors	O
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+.	O
+
+This	O
+process	O
+of	O
+selection	O
+started	O
+during	O
+the	O
+last	O
+quarter	O
+of	O
+the	O
+20th	O
+century	O
+,	O
+during	O
+which	O
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+frequency	O
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+(	O
+TT	O
+)	O
+rose	O
+significantly	O
+from	O
+14	O
+%	O
+to	O
+24	O
+%	O
+.	O
+
+We	O
+propose	O
+that	O
+this	O
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+due	O
+to	O
+the	O
+inclusion	O
+of	O
+an	O
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+factor	O
+that	O
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+.	O
+
+If	O
+we	O
+apply	O
+the	O
+mathematical	O
+model	O
+for	O
+dynamic	O
+selection	O
+developed	O
+for	O
+diploid	O
+organisms	O
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+sexual	O
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+,	O
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+T	O
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+could	O
+reach	O
+to	O
+90	O
+%	O
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+seven	O
+generations	O
+in	O
+our	O
+population	O
+(	O
+Figure	O
+1A	O
+)	O
+.	O
+
+However	O
+,	O
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+that	O
+applies	O
+to	O
+all	O
+individuals	O
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+the	O
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+.	O
+
+In	O
+our	O
+case	O
+,	O
+we	O
+suggest	O
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+factor	O
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+folate	O
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+intake	O
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+in	O
+periconceptional	O
+period	O
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+not	O
+affect	O
+to	O
+all	O
+individuals	O
+[	O
+18	O
+,	O
+19	O
+]	O
+.	O
+
+We	O
+assume	O
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+classic	O
+selection	O
+model	O
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+this	O
+case	O
+is	O
+only	O
+theoretical	O
+.	O
+
+On	O
+the	O
+basis	O
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+a	O
+competition	O
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+alleles	O
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+which	O
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+environmental	O
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+allele	O
+versus	O
+the	O
+other	O
+,	O
+the	O
+final	O
+result	O
+would	O
+be	O
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+by	O
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+previous	O
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+model	O
+.	O
+
+However	O
+in	O
+this	O
+case	O
+,	O
+the	O
+environment	O
+is	O
+not	O
+selecting	O
+against	O
+the	O
+wild	O
+type	O
+allele	O
+but	O
+rather	O
+allowing	O
+the	O
+survival	O
+of	O
+more	O
+mutated	O
+alleles	O
+.	O
+
+Therefore	O
+,	O
+the	O
+expected	O
+result	O
+would	O
+be	O
+not	O
+a	O
+systematic	O
+increase	O
+of	O
+the	O
+mutated	O
+allele	O
+but	O
+the	O
+creation	O
+of	O
+an	O
+allelic	O
+balance	O
+dependent	O
+on	O
+vitamin	O
+and	O
+folate	O
+abundance	O
+conditions	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+the	O
+mutation	O
+would	O
+have	O
+a	O
+lower	O
+influence	O
+on	O
+fetal	O
+viability	O
+(	O
+Figure	O
+1B	O
+)	O
+.	O
+
+The	O
+results	O
+showed	O
+an	O
+increase	O
+in	O
+mutated	O
+genotypes	O
+(	O
+CT	O
+and	O
+TT	O
+)	O
+and	O
+a	O
+strong	O
+protection	O
+against	O
+abortion	O
+by	O
+the	O
+wild	O
+type	O
+genotype	O
+(	O
+CC	O
+)	O
+,	O
+which	O
+is	O
+practically	O
+non	O
+-	O
+existent	O
+in	O
+the	O
+SA	O
+group	O
+.	O
+
+The	O
+frequency	O
+of	O
+the	O
+CC	O
+genotype	O
+shows	O
+no	O
+change	O
+over	O
+the	O
+decade	O
+studied	O
+(	O
+1980	O
+-	O
+1989	O
+)	O
+,	O
+which	O
+indicates	O
+that	O
+folate	O
+does	O
+not	O
+exert	O
+a	O
+visible	O
+effect	O
+on	O
+this	O
+genotype	O
+.	O
+
+However	O
+,	O
+the	O
+frequency	O
+of	O
+the	O
+mutated	O
+allele	O
+increases	O
+during	O
+this	O
+decade	O
+,	O
+especially	O
+in	O
+fetuses	O
+from	O
+abortions	O
+,	O
+and	O
+this	O
+increase	O
+correlated	O
+with	O
+the	O
+increase	O
+of	O
+the	O
+T	O
+allele	O
+in	O
+the	O
+control	O
+population	O
+.	O
+
+This	O
+finding	O
+suggests	O
+that	O
+the	O
+effect	O
+of	O
+folate	O
+is	O
+crucial	O
+to	O
+viability	O
+during	O
+the	O
+early	O
+stages	O
+of	O
+embryonic	O
+development	O
+,	O
+but	O
+,	O
+even	O
+with	O
+folate	O
+,	O
+not	O
+all	O
+embryos	O
+will	O
+survive	O
+until	O
+birth	O
+.	O
+
+In	O
+this	O
+population	O
+,	O
+the	O
+mutant	O
+allele	O
+with	O
+lower	O
+enzymatic	O
+activity	O
+has	O
+higher	O
+fitness	O
+than	O
+the	O
+wild	O
+type	O
+.	O
+
+In	O
+the	O
+folate	O
+cycle	O
+,	O
+it	O
+can	O
+be	O
+observed	O
+that	O
+5	O
+,	O
+10	O
+-	O
+methyleneTHF	O
+availability	O
+may	O
+be	O
+important	O
+.	O
+
+5	O
+,	O
+10	O
+-	O
+methyleneTHF	O
+is	O
+the	O
+substrate	O
+for	O
+several	O
+reactions	O
+in	O
+the	O
+cycle	O
+,	O
+but	O
+two	O
+of	O
+them	O
+(	O
+5	O
+-	O
+methylTHF	O
+and	O
+thymidilate	O
+synthesis	O
+)	O
+might	O
+be	O
+essential	O
+for	O
+embryo	O
+development	O
+in	O
+folate	O
+deficiency	O
+conditions	O
+.	O
+
+In	O
+both	O
+cases	O
+,	O
+complete	O
+or	O
+limited	O
+MTHFR	O
+activity	O
+will	O
+produce	O
+higher	O
+or	O
+lower	O
+5	O
+,	O
+10	O
+-	O
+methyleneTHF	O
+availability	O
+,	O
+which	O
+might	O
+be	O
+an	O
+essential	O
+factor	O
+for	O
+embryo	O
+development	O
+,	O
+such	O
+that	O
+a	O
+greater	O
+folate	O
+levels	O
+can	O
+compensate	O
+the	O
+lower	O
+enzymatic	O
+activity	O
+of	O
+the	O
+mutant	O
+.	O
+
+The	O
+implications	O
+of	O
+this	O
+polymorphism	O
+in	O
+nucleotide	O
+synthesis	O
+have	O
+not	O
+yet	O
+been	O
+determined	O
+,	O
+but	O
+certain	O
+data	O
+,	O
+such	O
+as	O
+high	O
+levels	O
+of	O
+uric	O
+acid	O
+found	O
+in	O
+mutated	O
+subjects	O
+[	O
+22	O
+,	O
+23	O
+]	O
+,	O
+suggest	O
+that	O
+there	O
+are	O
+different	O
+turnover	O
+rates	O
+associated	O
+with	O
+different	O
+polymorphisms	O
+.	O
+
+Conclusion	O
+
+We	O
+suggest	O
+that	O
+there	O
+is	O
+genetic	O
+selection	O
+in	O
+our	O
+population	O
+for	O
+the	O
+T	O
+allele	O
+of	O
+the	O
+MTHFR	O
+-	O
+677C	O
+>	O
+T	O
+polymorphism	O
+,	O
+whose	O
+origin	O
+could	O
+be	O
+an	O
+increase	O
+in	O
+fetal	O
+viability	O
+during	O
+the	O
+early	O
+stages	O
+of	O
+embryonic	O
+development	O
+because	O
+of	O
+an	O
+increase	O
+in	O
+folate	O
+and	O
+vitamin	O
+intake	O
+by	O
+women	B
+in	O
+the	O
+periconceptional	O
+period	O
+that	O
+began	O
+to	O
+be	O
+established	O
+in	O
+Spain	O
+in	O
+the	O
+last	O
+quarter	O
+of	O
+the	O
+20th	O
+century	O
+[	O
+18	O
+,	O
+19	O
+]	O
+.	O
+
+Higher	O
+frequencies	O
+for	O
+the	O
+T	O
+allele	O
+and	O
+TT	O
+genotype	O
+in	O
+our	O
+population	O
+are	O
+observed	O
+in	O
+the	O
+living	O
+and	O
+SA	O
+populations	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+authors	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+AMO	O
+performed	O
+the	O
+statistical	O
+analysis	O
+,	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+and	O
+revised	O
+it	O
+for	O
+publication	O
+.	O
+
+GC	O
+is	O
+the	O
+corresponding	O
+author	O
+,	O
+participated	O
+in	O
+the	O
+acquisition	O
+of	O
+samples	O
+and	O
+carried	O
+out	O
+the	O
+genotyping	O
+.	O
+
+ARP	O
+carried	O
+out	O
+the	O
+bibliographic	O
+search	O
+and	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+.	O
+
+AJJ	O
+participated	O
+in	O
+the	O
+selection	O
+and	O
+the	O
+processing	O
+of	O
+samples	O
+.	O
+
+MJG	O
+coordinated	O
+the	O
+laboratory	O
+work	O
+and	O
+selected	O
+the	O
+genotyping	O
+method	O
+.	O
+
+AR	O
+selected	O
+the	O
+control	O
+subjects	O
+and	O
+designed	O
+the	O
+consent	O
+form	O
+.	O
+
+MR	O
+helped	O
+in	O
+the	O
+interpretation	O
+of	O
+data	O
+and	O
+tables	O
+performance	O
+.	O
+
+ARE	O
+conceived	O
+the	O
+study	O
+and	O
+is	O
+the	O
+guarantor	O
+of	O
+this	O
+work	O
+and	O
+the	O
+general	O
+coordinator	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+Protein	O
+subfamily	O
+assignment	O
+using	O
+the	O
+Conserved	O
+Domain	O
+Database	O
+
+Abstract	O
+
+Background	O
+
+Domains	O
+,	O
+evolutionarily	O
+conserved	O
+units	O
+of	O
+proteins	O
+,	O
+are	O
+widely	O
+used	O
+to	O
+classify	O
+protein	O
+sequences	O
+and	O
+infer	O
+protein	O
+function	O
+.	O
+
+Often	O
+,	O
+two	O
+or	O
+more	O
+overlapping	O
+domain	O
+models	O
+match	O
+a	O
+region	O
+of	O
+a	O
+protein	O
+sequence	O
+.	O
+
+Therefore	O
+,	O
+procedures	O
+are	O
+required	O
+to	O
+choose	O
+appropriate	O
+domain	O
+annotations	O
+for	O
+the	O
+protein	O
+.	O
+
+Here	O
+,	O
+we	O
+propose	O
+a	O
+method	O
+for	O
+assigning	O
+NCBI	O
+-	O
+curated	O
+domains	O
+from	O
+the	O
+Curated	O
+Domain	O
+Database	O
+(	O
+CDD	O
+)	O
+that	O
+takes	O
+into	O
+account	O
+the	O
+organization	O
+of	O
+the	O
+domains	O
+into	O
+hierarchies	O
+of	O
+homologous	O
+domain	O
+models	O
+.	O
+
+Findings	O
+
+Our	O
+analysis	O
+of	O
+alignment	O
+scores	O
+from	O
+NCBI	O
+-	O
+curated	O
+domain	O
+assignments	O
+suggests	O
+that	O
+identifying	O
+the	O
+correct	O
+model	O
+among	O
+closely	O
+related	O
+models	O
+is	O
+more	O
+difficult	O
+than	O
+choosing	O
+between	O
+non	O
+-	O
+overlapping	O
+domain	O
+models	O
+.	O
+
+We	O
+find	O
+that	O
+simple	O
+heuristics	O
+based	O
+on	O
+sorting	O
+scores	O
+and	O
+domain	O
+-	O
+specific	O
+thresholds	O
+are	O
+effective	O
+at	O
+reducing	O
+classification	O
+error	O
+.	O
+
+In	O
+fact	O
+,	O
+in	O
+our	O
+test	O
+set	O
+,	O
+the	O
+heuristics	O
+result	O
+in	O
+almost	O
+90	O
+%	O
+of	O
+current	O
+misclassifications	O
+due	O
+to	O
+missing	O
+domain	O
+subfamilies	O
+being	O
+replaced	O
+by	O
+more	O
+generic	O
+domain	O
+assignments	O
+,	O
+thereby	O
+eliminating	O
+a	O
+significant	O
+amount	O
+of	O
+error	O
+within	O
+the	O
+database	O
+.	O
+
+Conclusion	O
+
+Our	O
+proposed	O
+domain	O
+subfamily	O
+assignment	O
+rule	O
+has	O
+been	O
+incorporated	O
+into	O
+the	O
+CD	O
+-	O
+Search	O
+software	O
+for	O
+assigning	O
+CDD	O
+domains	O
+to	O
+query	O
+protein	O
+sequences	O
+and	O
+has	O
+significantly	O
+improved	O
+pre	O
+-	O
+calculated	O
+domain	O
+annotations	O
+on	O
+protein	O
+sequences	O
+in	O
+NCBI	O
+'	O
+s	O
+Entrez	O
+resource	O
+.	O
+
+Background	O
+
+A	O
+major	O
+goal	O
+in	O
+the	O
+post	O
+-	O
+genomic	O
+world	O
+is	O
+to	O
+infer	O
+protein	O
+function	O
+from	O
+sequence	O
+information	O
+.	O
+
+One	O
+popular	O
+approach	O
+is	O
+to	O
+classify	O
+protein	O
+families	O
+or	O
+domains	O
+by	O
+grouping	O
+homologous	O
+sequences	O
+and	O
+annotating	O
+the	O
+groups	O
+with	O
+properties	O
+such	O
+as	O
+general	O
+function	O
+,	O
+intracellular	O
+location	O
+,	O
+three	O
+-	O
+dimensional	O
+structure	O
+,	O
+conserved	O
+sequence	O
+patterns	O
+or	O
+motifs	O
+,	O
+evolutionary	O
+origin	O
+,	O
+and	O
+binding	O
+and	O
+active	O
+sites	O
+.	O
+
+Novel	O
+proteins	O
+can	O
+be	O
+characterized	O
+quickly	O
+by	O
+assigning	O
+a	O
+group	O
+via	O
+profile	O
+search	O
+methods	O
+.	O
+
+However	O
+,	O
+more	O
+than	O
+one	O
+family	O
+or	O
+subfamily	O
+may	O
+exhibit	O
+similarity	O
+to	O
+overlapping	O
+sequence	O
+intervals	O
+and	O
+to	O
+a	O
+degree	O
+that	O
+seems	O
+convincing	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Assigning	O
+the	O
+protein	O
+to	O
+the	O
+correct	O
+group	O
+not	O
+only	O
+yields	O
+the	O
+correct	O
+annotations	O
+,	O
+but	O
+may	O
+also	O
+help	O
+to	O
+avoid	O
+propagating	O
+annotation	O
+errors	O
+and	O
+alleviate	O
+current	O
+issues	O
+with	O
+mislabelling	O
+in	O
+protein	O
+sequence	O
+databases	O
+[	O
+1	O
+,	O
+2	O
+]	O
+.	O
+
+Here	O
+,	O
+we	O
+examine	O
+the	O
+problem	O
+of	O
+making	O
+correct	O
+domain	O
+assignments	O
+from	O
+the	O
+Conserved	O
+Domain	O
+Database	O
+[	O
+3	O
+,	O
+4	O
+]	O
+.	O
+
+Domains	O
+are	O
+evolutionarily	O
+conserved	O
+units	O
+in	O
+proteins	O
+and	O
+frequently	O
+correspond	O
+to	O
+recurrent	O
+structural	O
+and	O
+functional	O
+units	O
+.	O
+
+The	O
+particular	O
+function	O
+of	O
+a	O
+protein	O
+depends	O
+on	O
+its	O
+combination	O
+of	O
+domains	O
+;	O
+two	O
+-	O
+thirds	O
+of	O
+prokaryotic	O
+proteins	O
+and	O
+80	O
+%	O
+of	O
+eukaryotic	O
+proteins	O
+have	O
+more	O
+than	O
+one	O
+domain	O
+.	O
+
+To	O
+create	O
+new	O
+protein	O
+functions	O
+,	O
+novel	O
+domain	O
+architectures	O
+arise	O
+through	O
+domain	O
+rearrangement	O
+and	O
+recombination	O
+,	O
+frequently	O
+through	O
+gene	O
+duplication	O
+and	O
+fission	O
+or	O
+fusion	O
+events	O
+[	O
+5	O
+,	O
+6	O
+]	O
+.	O
+
+A	O
+domain	O
+may	O
+be	O
+represented	O
+as	O
+a	O
+multiple	O
+sequence	O
+alignment	O
+(	O
+MSA	O
+)	O
+of	O
+homologous	O
+sequence	O
+fragments	O
+.	O
+
+To	O
+identify	O
+the	O
+domains	O
+in	O
+a	O
+query	O
+protein	O
+sequence	O
+,	O
+the	O
+MSAs	O
+are	O
+converted	O
+into	O
+scoring	O
+models	O
+such	O
+as	O
+hidden	O
+Markov	O
+model	O
+or	O
+position	O
+-	O
+specific	O
+scoring	O
+matrix	O
+for	O
+use	O
+with	O
+database	O
+search	O
+algorithms	O
+such	O
+HMMER	O
+[	O
+7	O
+]	O
+and	O
+RPS	O
+-	O
+BLAST	O
+[	O
+8	O
+]	O
+.	O
+
+To	O
+refine	O
+protein	O
+annotation	O
+,	O
+domains	O
+models	O
+may	O
+be	O
+subdivided	O
+to	O
+represent	O
+more	O
+specific	O
+functions	O
+or	O
+conserved	O
+features	O
+.	O
+
+CDD	O
+curators	O
+apply	O
+phylogenetic	O
+and	O
+structural	O
+analysis	O
+to	O
+construct	O
+hierarchies	O
+of	O
+homologous	O
+domain	O
+models	O
+,	O
+related	O
+by	O
+common	O
+descent	O
+,	O
+to	O
+reflect	O
+aspects	O
+of	O
+their	O
+evolutionary	O
+histories	O
+[	O
+3	O
+,	O
+4	O
+]	O
+.	O
+
+Curation	O
+follows	O
+an	O
+iterative	O
+procedure	O
+to	O
+split	O
+domain	O
+models	O
+into	O
+subfamilies	O
+that	O
+redistributes	O
+sequences	O
+into	O
+more	O
+narrowly	O
+defined	O
+models	O
+.	O
+
+In	O
+the	O
+hierarchy	O
+tree	O
+structure	O
+,	O
+the	O
+leaf	O
+domains	O
+represent	O
+highly	O
+conserved	O
+and	O
+often	O
+orthologous	O
+protein	O
+subgroups	O
+.	O
+
+Their	O
+precursor	O
+(	O
+internal	O
+)	O
+domains	O
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+reflect	O
+ancient	O
+gene	O
+duplication	O
+events	O
+,	O
+as	O
+CDD	O
+aims	O
+to	O
+categorize	O
+ancient	O
+conserved	O
+domain	O
+families	O
+.	O
+
+It	O
+may	O
+seem	O
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+that	O
+once	O
+the	O
+profiles	O
+have	O
+been	O
+defined	O
+,	O
+the	O
+most	O
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+match	O
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+a	O
+query	O
+sequence	O
+is	O
+the	O
+correct	O
+one	O
+.	O
+
+Indeed	O
+,	O
+domains	O
+from	O
+Pfam	O
+[	O
+9	O
+,	O
+10	O
+]	O
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+SMART	O
+[	O
+11	O
+]	O
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+the	O
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+-	O
+value	O
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+exceeds	O
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+-	O
+specific	O
+cutoff	O
+[	O
+12	O
+,	O
+13	O
+]	O
+.	O
+
+This	O
+straightforward	O
+approach	O
+works	O
+well	O
+when	O
+the	O
+candidate	O
+domains	O
+are	O
+disjoint	O
+.	O
+
+Domain	O
+subfamilies	O
+may	O
+be	O
+obtained	O
+through	O
+automated	O
+methods	O
+such	O
+as	O
+the	O
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+-	O
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+for	O
+identifying	O
+functional	O
+subtypes	O
+of	O
+known	O
+domain	O
+families	O
+[	O
+14	O
+,	O
+15	O
+]	O
+or	O
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+mirroring	O
+other	O
+hierarchical	O
+domain	O
+classifications	O
+such	O
+as	O
+SCOP	O
+[	O
+16	O
+]	O
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+CATH	O
+[	O
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+]	O
+.	O
+
+However	O
+,	O
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+generally	O
+attempt	O
+to	O
+classify	O
+a	O
+member	O
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+a	O
+family	O
+at	O
+the	O
+subfamily	O
+level	O
+given	O
+that	O
+the	O
+family	O
+is	O
+known	O
+,	O
+as	O
+in	O
+a	O
+statistical	O
+pairwise	O
+/	O
+profile	O
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+proposed	O
+for	O
+SUPERFAMILY	O
+[	O
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+-	O
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+
+The	O
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+CDD	O
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+identifying	O
+the	O
+most	O
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+level	O
+of	O
+resolution	O
+among	O
+domain	O
+models	O
+that	O
+offer	O
+more	O
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+-	O
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+descriptions	O
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+protein	O
+.	O
+
+We	O
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+the	O
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+subgroup	O
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+,	O
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+model	O
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+
+Consequently	O
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+,	O
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+,	O
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+
+Here	O
+,	O
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+
+The	O
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+,	O
+as	O
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+is	O
+efficient	O
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+makes	O
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+
+Constructing	O
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+set	O
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+To	O
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+heuristics	O
+,	O
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+-	O
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+.	O
+
+2	O
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+
+This	O
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+.	O
+
+The	O
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+-	O
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+distributions	O
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+representative	O
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+.	O
+
+The	O
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+.	O
+
+Two	O
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+one	O
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+%	O
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+.	O
+
+While	O
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+sequence	O
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+placed	O
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+model	O
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+characterizes	O
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+,	O
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+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Sequences	O
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+
+Non	O
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+.	O
+
+Alignments	O
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+-	O
+curated	O
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+in	O
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+time	O
+of	O
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+(	O
+September	O
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+)	O
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+-	O
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+RPS	O
+-	O
+BLAST	O
+.	O
+
+In	O
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+analysis	O
+,	O
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+to	O
+the	O
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+,	O
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+of	O
+the	O
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+,	O
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+allows	O
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+compared	O
+.	O
+
+The	O
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+roughly	O
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+-	O
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+.	O
+
+A	O
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+-	O
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+,	O
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+
+We	O
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+.	O
+
+Other	O
+hits	O
+to	O
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+the	O
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+
+CDD	O
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+-	O
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+,	O
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+-	O
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+"	O
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+
+Many	O
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+Among	O
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+,	O
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+
+This	O
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+
+Performance	O
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+We	O
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+
+The	O
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+-	O
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+
+Analysis	O
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+
+Further	O
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+-	O
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+
+For	O
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+-	O
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+some	O
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+/	O
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+/	O
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+
+Child	O
+/	O
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+
+These	O
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+,	O
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+,	O
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+
+In	O
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+,	O
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+/	O
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+.	O
+
+For	O
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+,	O
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+
+We	O
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+
+This	O
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+,	O
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+,	O
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+
+The	O
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+-	O
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+,	O
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+,	O
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+
+The	O
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+,	O
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+,	O
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+-	O
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+
+Proposed	O
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+
+We	O
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+-	O
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+,	O
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+.	O
+
+Sequence	O
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+following	O
+this	O
+rule	O
+may	O
+receive	O
+only	O
+generic	O
+domain	O
+assignments	O
+.	O
+
+Assuming	O
+that	O
+the	O
+set	O
+of	O
+overlapping	O
+domains	O
+represents	O
+an	O
+ancient	O
+domain	O
+superfamily	O
+,	O
+such	O
+a	O
+generic	O
+assignment	O
+would	O
+be	O
+characterized	O
+as	O
+membership	O
+with	O
+the	O
+respective	O
+superfamily	O
+.	O
+
+Reducing	O
+misclassifications	O
+and	O
+errors	O
+due	O
+to	O
+missing	O
+subfamilies	O
+
+A	O
+more	O
+concrete	O
+picture	O
+of	O
+the	O
+effect	O
+of	O
+the	O
+proposed	O
+rule	O
+may	O
+be	O
+gleaned	O
+by	O
+quantifying	O
+misclassifications	O
+,	O
+defined	O
+to	O
+be	O
+either	O
+descendants	O
+of	O
+the	O
+correct	O
+domain	O
+or	O
+domains	O
+that	O
+lie	O
+in	O
+other	O
+branches	O
+of	O
+the	O
+correct	O
+hierarchy	O
+.	O
+
+Averaged	O
+over	O
+domains	O
+in	O
+multi	O
+-	O
+domain	O
+hierarchies	O
+and	O
+counting	O
+only	O
+sequences	O
+with	O
+self	O
+hits	O
+,	O
+the	O
+misclassification	O
+rate	O
+using	O
+high	O
+scores	O
+only	O
+is	O
+2	O
+.	O
+6	O
+%	O
+.	O
+
+Incorporating	O
+score	O
+thresholds	O
+to	O
+eliminate	O
+low	O
+-	O
+scoring	O
+best	O
+hits	O
+reduces	O
+the	O
+misclassification	O
+rate	O
+to	O
+0	O
+.	O
+85	O
+%	O
+.	O
+
+Misclassifications	O
+may	O
+also	O
+be	O
+used	O
+to	O
+estimate	O
+error	O
+due	O
+to	O
+missing	O
+subfamilies	O
+.	O
+
+Not	O
+all	O
+subclasses	O
+in	O
+a	O
+domain	O
+hierarchy	O
+may	O
+have	O
+been	O
+identified	O
+as	O
+the	O
+available	O
+sequence	O
+databases	O
+only	O
+provide	O
+a	O
+terse	O
+snapshot	O
+of	O
+protein	O
+domain	O
+diversity	O
+.	O
+
+We	O
+simulate	O
+a	O
+cross	O
+-	O
+validation	O
+experiment	O
+to	O
+ask	O
+,	O
+if	O
+an	O
+existing	O
+domain	O
+model	O
+were	O
+missing	O
+from	O
+a	O
+hierarchy	O
+,	O
+what	O
+fraction	O
+of	O
+its	O
+sequence	O
+intervals	O
+have	O
+best	O
+hits	O
+to	O
+other	O
+models	O
+in	O
+the	O
+hierarchy	O
+that	O
+are	O
+not	O
+ancestors	O
+of	O
+the	O
+correct	O
+model	O
+?	O
+
+Averaged	O
+over	O
+leaf	O
+domains	O
+,	O
+50	O
+.	O
+9	O
+%	O
+of	O
+domain	O
+assignments	O
+made	O
+from	O
+high	O
+alignment	O
+score	O
+alone	O
+are	O
+misclassifications	O
+,	O
+compared	O
+to	O
+6	O
+.	O
+0	O
+%	O
+of	O
+domain	O
+assignments	O
+after	O
+thresholds	O
+are	O
+used	O
+to	O
+screen	O
+hits	O
+.	O
+
+Function	O
+and	O
+classification	O
+through	O
+specific	O
+domain	O
+assignments	O
+:	O
+Glycyl	O
+radical	O
+enzymes	O
+
+To	O
+illustrate	O
+the	O
+effect	O
+of	O
+our	O
+proposed	O
+method	O
+,	O
+we	O
+examine	O
+domain	O
+assignments	O
+from	O
+the	O
+glycyl	O
+radical	O
+enzymes	O
+(	O
+RNR	O
+_	O
+PFL	O
+hierarchy	O
+)	O
+.	O
+
+Its	O
+subgroups	O
+have	O
+distinct	O
+and	O
+important	O
+functions	O
+,	O
+including	O
+ribonucleotide	O
+reductases	O
+(	O
+RNRs	O
+)	O
+,	O
+which	O
+synthesize	O
+deoxyribonucleotides	O
+,	O
+and	O
+pyruvate	O
+-	O
+formate	O
+lysases	O
+(	O
+PFLs	O
+)	O
+,	O
+a	O
+family	O
+of	O
+catabolic	O
+enzymes	O
+.	O
+
+The	O
+proposed	O
+method	O
+places	O
+the	O
+sequence	O
+[	O
+Entrez	O
+:	O
+CAA42118	O
+]	O
+into	O
+RNR	O
+class	O
+1	O
+and	O
+places	O
+[	O
+Entrez	O
+:	O
+AAZ61477	O
+]	O
+into	O
+RNR	O
+class	O
+-	O
+1	O
+-	O
+like	O
+domain	O
+.	O
+
+The	O
+functions	O
+of	O
+these	O
+proteins	O
+are	O
+inferred	O
+by	O
+their	O
+subclass	O
+.	O
+
+Other	O
+proteins	O
+receive	O
+generic	O
+assignments	O
+to	O
+this	O
+family	O
+.	O
+
+For	O
+example	O
+,	O
+PFL2	O
+(	O
+cd01677	O
+)	O
+is	O
+the	O
+best	O
+match	O
+to	O
+[	O
+Entrez	O
+:	O
+ABX41552	O
+]	O
+and	O
+[	O
+Entrez	O
+:	O
+EDQ26237	O
+]	O
+with	O
+alignment	O
+scores	O
+that	O
+fall	O
+short	O
+of	O
+the	O
+PFL2	O
+threshold	O
+.	O
+
+The	O
+first	O
+alignment	O
+includes	O
+a	O
+long	O
+insertion	O
+(	O
+gap	O
+)	O
+,	O
+and	O
+the	O
+latter	O
+exhibits	O
+weak	O
+sequence	O
+similarity	O
+;	O
+in	O
+both	O
+of	O
+these	O
+scenarios	O
+the	O
+transfer	O
+of	O
+functional	O
+annotation	O
+may	O
+not	O
+be	O
+straightforward	O
+.	O
+
+Domain	O
+assignments	O
+also	O
+help	O
+to	O
+make	O
+biological	O
+insights	O
+.	O
+
+RNRs	O
+fall	O
+into	O
+classes	O
+that	O
+use	O
+different	O
+mechanisms	O
+and	O
+/	O
+or	O
+cofactors	O
+.	O
+
+Class	O
+1	O
+is	O
+oxygen	O
+dependent	O
+and	O
+class	O
+3	O
+is	O
+used	O
+by	O
+strictly	O
+or	O
+facultative	O
+anaerobic	O
+organisms	O
+.	O
+
+RNR	O
+_	O
+1	O
+_	O
+like	O
+has	O
+a	O
+similar	O
+active	O
+site	O
+to	O
+class	O
+1	O
+and	O
+at	O
+the	O
+time	O
+of	O
+curation	O
+,	O
+no	O
+specific	O
+literature	O
+was	O
+available	O
+about	O
+this	O
+subclass	O
+.	O
+
+We	O
+observed	O
+that	O
+the	O
+strictly	O
+anaerobic	O
+organism	O
+Chlorobium	B
+limicola	I
+DSM	O
+24	O
+has	O
+RNR	O
+_	O
+3	O
+proteins	O
+(	O
+e	O
+.	O
+g	O
+.	O
+[	O
+Entrez	O
+:	O
+ZP	O
+_	O
+00512827	O
+]	O
+)	O
+as	O
+well	O
+as	O
+an	O
+enzyme	O
+(	O
+[	O
+Entrez	O
+:	O
+ZP	O
+_	O
+00512727	O
+]	O
+)	O
+that	O
+matches	O
+RNR	O
+_	O
+1	O
+_	O
+like	O
+,	O
+suggesting	O
+that	O
+RNR	O
+_	O
+1	O
+_	O
+like	O
+,	O
+a	O
+subfamily	O
+lacking	O
+experimental	O
+characterization	O
+,	O
+may	O
+contain	O
+non	O
+-	O
+oxygen	O
+dependent	O
+versions	O
+of	O
+RNR	O
+_	O
+1	O
+.	O
+
+Discussion	O
+
+While	O
+many	O
+sequences	O
+can	O
+be	O
+classified	O
+by	O
+sequence	O
+similarity	O
+,	O
+profiles	O
+of	O
+protein	O
+domain	O
+families	O
+make	O
+it	O
+possible	O
+to	O
+quickly	O
+classify	O
+more	O
+distant	O
+homologs	O
+[	O
+23	O
+]	O
+and	O
+can	O
+better	O
+handle	O
+multi	O
+-	O
+domain	O
+proteins	O
+.	O
+
+An	O
+important	O
+step	O
+in	O
+transferring	O
+annotations	O
+from	O
+known	O
+protein	O
+families	O
+is	O
+identifying	O
+the	O
+subclass	O
+that	O
+provides	O
+the	O
+best	O
+characterization	O
+for	O
+the	O
+protein	O
+.	O
+
+Here	O
+,	O
+we	O
+conducted	O
+the	O
+first	O
+focused	O
+analysis	O
+of	O
+domain	O
+assignments	O
+from	O
+CDD	O
+in	O
+order	O
+to	O
+assess	O
+existing	O
+methods	O
+for	O
+domain	O
+and	O
+domain	O
+subfamily	O
+assignment	O
+and	O
+identify	O
+ways	O
+to	O
+improve	O
+the	O
+quality	O
+of	O
+assignments	O
+.	O
+
+We	O
+find	O
+that	O
+best	O
+-	O
+scoring	O
+hits	O
+are	O
+sometimes	O
+too	O
+specific	O
+,	O
+causing	O
+a	O
+sequence	O
+to	O
+be	O
+mislabelled	O
+by	O
+a	O
+subfamily	O
+of	O
+the	O
+correct	O
+domain	O
+.	O
+
+We	O
+propose	O
+a	O
+subclass	O
+assignment	O
+procedure	O
+that	O
+enables	O
+concrete	O
+assignments	O
+,	O
+computed	O
+quickly	O
+using	O
+existing	O
+data	O
+,	O
+and	O
+demonstrate	O
+that	O
+this	O
+procedure	O
+largely	O
+avoids	O
+over	O
+-	O
+predictions	O
+or	O
+false	O
+positive	O
+assignments	O
+and	O
+is	O
+robust	O
+enough	O
+to	O
+deal	O
+with	O
+situations	O
+such	O
+as	O
+incomplete	O
+hierarchies	O
+in	O
+which	O
+not	O
+all	O
+subfamilies	O
+have	O
+been	O
+identified	O
+.	O
+
+We	O
+elected	O
+to	O
+not	O
+employ	O
+standard	O
+jack	O
+-	O
+knife	O
+or	O
+cross	O
+-	O
+validation	O
+testing	O
+for	O
+a	O
+sequence	O
+against	O
+its	O
+correct	O
+domain	O
+,	O
+as	O
+the	O
+task	O
+is	O
+to	O
+classify	O
+sequence	O
+fragments	O
+that	O
+are	O
+very	O
+similar	O
+to	O
+a	O
+subfamily	O
+,	O
+where	O
+the	O
+subfamily	O
+model	O
+is	O
+also	O
+constructed	O
+from	O
+very	O
+similar	O
+sequences	O
+.	O
+
+Although	O
+the	O
+sequence	O
+and	O
+domain	O
+databases	O
+evolve	O
+rapidly	O
+,	O
+we	O
+expect	O
+our	O
+findings	O
+to	O
+provide	O
+an	O
+accurate	O
+snapshot	O
+for	O
+some	O
+time	O
+.	O
+
+A	O
+version	O
+of	O
+our	O
+proposed	O
+method	O
+has	O
+been	O
+incorporated	O
+into	O
+the	O
+current	O
+version	O
+of	O
+the	O
+CD	O
+-	O
+Search	O
+program	O
+and	O
+the	O
+pre	O
+-	O
+calculated	O
+annotation	O
+of	O
+proteins	O
+with	O
+domains	O
+in	O
+NCBI	O
+'	O
+s	O
+Entrez	O
+system	O
+.	O
+
+Domain	O
+assignments	O
+to	O
+specific	O
+orthologous	O
+subfamilies	O
+or	O
+ancient	O
+subfamilies	O
+are	O
+distinguished	O
+from	O
+non	O
+-	O
+specific	O
+assignments	O
+to	O
+a	O
+domain	O
+superfamily	O
+.	O
+
+High	O
+-	O
+confidence	O
+annotation	O
+of	O
+functional	O
+sites	O
+is	O
+also	O
+provided	O
+following	O
+these	O
+results	O
+.	O
+
+We	O
+hope	O
+the	O
+improved	O
+ability	O
+to	O
+quickly	O
+and	O
+accurately	O
+classify	O
+proteins	O
+will	O
+be	O
+a	O
+valuable	O
+step	O
+toward	O
+simplifying	O
+protein	O
+sequence	O
+analysis	O
+and	O
+the	O
+computational	O
+annotation	O
+of	O
+genomes	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+authors	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+JF	O
+carried	O
+out	O
+the	O
+experiments	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+AMB	O
+conceived	O
+the	O
+study	O
+,	O
+participated	O
+in	O
+its	O
+design	O
+,	O
+and	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+.	O
+
+Supplementary	O
+Material	O
+
+Identification	O
+of	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+for	O
+rehabilitation	O
+professionals	O
+in	O
+Ontario	O
+,	O
+Canada	O
+:	O
+results	O
+from	O
+expert	O
+panels	O
+
+Abstract	O
+
+Background	O
+
+Demand	O
+for	O
+rehabilitation	O
+services	O
+is	O
+expected	O
+to	O
+increase	O
+due	O
+to	O
+factors	O
+such	O
+as	O
+an	O
+aging	O
+population	O
+,	O
+workforce	O
+pressures	O
+,	O
+rise	O
+in	O
+chronic	O
+and	O
+complex	O
+multi	O
+-	O
+system	O
+disorders	O
+,	O
+advances	O
+in	O
+technology	O
+,	O
+and	O
+changes	O
+in	O
+interprofessional	O
+health	O
+service	O
+delivery	O
+models	O
+.	O
+
+However	O
+,	O
+health	O
+human	B
+resource	O
+(	O
+HHR	O
+)	O
+strategies	O
+for	O
+Canadian	O
+rehabilitation	O
+professionals	O
+are	O
+lagging	O
+behind	O
+other	O
+professional	O
+groups	O
+such	O
+as	O
+physicians	O
+and	O
+nurses	O
+.	O
+
+The	O
+objectives	O
+of	O
+this	O
+study	O
+were	O
+:	O
+1	O
+)	O
+to	O
+identify	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+of	O
+rehabilitation	O
+professionals	O
+including	O
+occupational	O
+therapists	O
+,	O
+physical	O
+therapists	O
+and	O
+speech	O
+language	O
+pathologists	O
+from	O
+the	O
+literature	O
+;	O
+and	O
+2	O
+)	O
+to	O
+investigate	O
+both	O
+the	O
+importance	O
+and	O
+feasibility	O
+of	O
+the	O
+identified	O
+strategies	O
+using	O
+expert	O
+panels	O
+amongst	O
+HHR	O
+and	O
+education	O
+experts	O
+.	O
+
+Methods	O
+
+A	O
+review	O
+of	O
+the	O
+literature	O
+was	O
+conducted	O
+to	O
+identify	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+for	O
+rehabilitation	O
+professionals	O
+.	O
+
+Two	O
+expert	O
+panels	O
+,	O
+one	O
+on	O
+Recruitment	O
+and	O
+Retention	O
+and	O
+the	O
+other	O
+on	O
+Education	O
+were	O
+convened	O
+to	O
+determine	O
+the	O
+importance	O
+and	O
+feasibility	O
+of	O
+the	O
+identified	O
+strategies	O
+.	O
+
+A	O
+modified	O
+-	O
+delphi	O
+process	O
+was	O
+used	O
+to	O
+gain	O
+consensus	O
+and	O
+to	O
+rate	O
+the	O
+identified	O
+strategies	O
+along	O
+these	O
+two	O
+dimensions	O
+.	O
+
+Results	O
+
+A	O
+total	O
+of	O
+34	O
+strategies	O
+were	O
+identified	O
+by	O
+the	O
+Recruitment	O
+and	O
+Retention	O
+and	O
+Education	O
+expert	O
+panels	O
+as	O
+being	O
+important	O
+and	O
+feasible	O
+for	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
+for	O
+recruitment	O
+and	O
+retention	O
+of	O
+rehabilitation	O
+professionals	O
+.	O
+
+Seven	O
+were	O
+categorized	O
+under	O
+the	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+theme	O
+,	O
+another	O
+seven	O
+in	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+,	O
+two	O
+in	O
+Workload	O
+and	O
+Skill	O
+Mix	O
+,	O
+thirteen	O
+in	O
+Professional	O
+Development	O
+and	O
+five	O
+in	O
+Education	O
+and	O
+Training	O
+.	O
+
+Conclusion	O
+
+Based	O
+on	O
+the	O
+results	O
+from	O
+the	O
+expert	O
+panels	O
+,	O
+the	O
+three	O
+major	O
+areas	O
+of	O
+focus	O
+for	O
+HHR	O
+planning	O
+in	O
+the	O
+rehabilitation	O
+sector	O
+should	O
+include	O
+strategies	O
+addressing	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+,	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+and	O
+Professional	O
+Development	O
+.	O
+
+Background	O
+
+Demand	O
+for	O
+rehabilitation	O
+services	O
+is	O
+expected	O
+to	O
+increase	O
+within	O
+the	O
+next	O
+decade	O
+primarily	O
+due	O
+to	O
+factors	O
+such	O
+as	O
+an	O
+aging	O
+population	O
+,	O
+workforce	O
+pressures	O
+,	O
+rise	O
+in	O
+chronic	O
+and	O
+complex	O
+multi	O
+-	O
+system	O
+disorders	O
+,	O
+advances	O
+in	O
+technology	O
+,	O
+and	O
+changes	O
+in	O
+health	O
+service	O
+delivery	O
+models	O
+[	O
+1	O
+-	O
+4	O
+]	O
+.	O
+
+In	O
+Canada	O
+,	O
+rehabilitation	O
+personnel	O
+constitute	O
+the	O
+third	O
+largest	O
+health	O
+professional	O
+group	O
+after	O
+nurses	O
+and	O
+physicians	O
+.	O
+
+Despite	O
+the	O
+size	O
+of	O
+this	O
+workforce	O
+,	O
+studies	O
+have	O
+consistently	O
+reported	O
+ongoing	O
+shortages	O
+of	O
+physiotherapists	O
+(	O
+PTs	O
+)	O
+,	O
+occupational	O
+therapists	O
+(	O
+OTs	O
+)	O
+and	O
+speech	O
+-	O
+language	O
+pathologists	O
+(	O
+SLPs	O
+)	O
+across	O
+all	O
+jurisdictions	O
+[	O
+5	O
+-	O
+7	O
+]	O
+.	O
+
+Similarly	O
+,	O
+recruitment	O
+and	O
+retention	O
+of	O
+rehabilitation	O
+professionals	O
+has	O
+been	O
+considered	O
+a	O
+challenge	O
+internationally	O
+,	O
+nationally	O
+and	O
+provincially	O
+.	O
+
+At	O
+the	O
+international	O
+level	O
+,	O
+the	O
+literature	O
+reports	O
+recruitment	O
+and	O
+retention	O
+difficulties	O
+of	O
+rehabilitation	O
+therapists	O
+in	O
+countries	O
+such	O
+as	O
+Australia	O
+,	O
+New	O
+Zealand	O
+,	O
+United	O
+Kingdom	O
+and	O
+the	O
+United	O
+States	O
+[	O
+8	O
+-	O
+13	O
+]	O
+.	O
+
+Provinces	O
+across	O
+Canada	O
+face	O
+similar	O
+issues	O
+;	O
+with	O
+Ontario	O
+projected	O
+to	O
+face	O
+the	O
+most	O
+difficulty	O
+due	O
+to	O
+its	O
+population	O
+growth	O
+rate	O
+[	O
+14	O
+]	O
+.	O
+
+Based	O
+on	O
+the	O
+Canadian	O
+Institute	O
+for	O
+Health	O
+Information	O
+'	O
+s	O
+Health	O
+Personnel	O
+Trends	O
+in	O
+Canada	O
+from	O
+1993	O
+to	O
+2002	O
+report	O
+,	O
+numerous	O
+factors	O
+have	O
+been	O
+suggested	O
+to	O
+influence	O
+demand	O
+for	O
+physiotherapy	O
+and	O
+occupational	O
+therapy	O
+services	O
+.	O
+
+Factors	O
+that	O
+may	O
+influence	O
+increase	O
+demand	O
+for	O
+physiotherapy	O
+include	O
+:	O
+shift	O
+in	O
+health	O
+service	O
+delivery	O
+models	O
+from	O
+hospital	O
+to	O
+community	O
+care	O
+;	O
+earlier	O
+patient	B
+discharge	O
+;	O
+increased	O
+expectations	O
+from	O
+aging	O
+Canadians	O
+concerning	O
+more	O
+active	O
+lifestyles	O
+;	O
+growing	O
+private	O
+practice	O
+sector	O
+and	O
+continued	O
+shortages	O
+for	O
+PTs	O
+in	O
+both	O
+private	O
+and	O
+public	O
+sectors	O
+in	O
+rural	O
+,	O
+remote	O
+and	O
+urban	O
+settings	O
+across	O
+Canada	O
+[	O
+2	O
+]	O
+.	O
+
+In	O
+1993	O
+,	O
+an	O
+Ontario	O
+study	O
+stated	O
+that	O
+in	O
+order	O
+to	O
+meet	O
+demands	O
+of	O
+changing	O
+health	O
+care	O
+policy	O
+,	O
+medical	O
+technology	O
+and	O
+demographic	O
+changes	O
+in	O
+the	O
+population	O
+,	O
+the	O
+PT	O
+profession	O
+required	O
+an	O
+annual	O
+growth	O
+rate	O
+of	O
+4	O
+.	O
+4	O
+%	O
+until	O
+the	O
+year	O
+2000	O
+[	O
+5	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+national	O
+health	O
+personnel	O
+databases	O
+revealed	O
+that	O
+the	O
+actual	O
+average	O
+annual	O
+growth	O
+rate	O
+of	O
+active	O
+PTs	O
+in	O
+Canada	O
+from	O
+1995	O
+to	O
+2004	O
+was	O
+only	O
+2	O
+.	O
+5	O
+%	O
+,	O
+approximately	O
+half	O
+of	O
+the	O
+projected	O
+requirement	O
+suggested	O
+to	O
+meet	O
+demand	O
+[	O
+15	O
+]	O
+.	O
+
+Similarly	O
+,	O
+in	O
+Ontario	O
+in	O
+the	O
+early	O
+1990s	O
+an	O
+increase	O
+in	O
+demand	O
+for	O
+OTs	O
+was	O
+projected	O
+because	O
+of	O
+the	O
+reported	O
+shortage	O
+in	O
+OTs	O
+and	O
+high	O
+attrition	O
+rate	O
+[	O
+16	O
+]	O
+.	O
+
+The	O
+shortage	O
+of	O
+OTs	O
+was	O
+explained	O
+by	O
+another	O
+Ontario	O
+study	O
+to	O
+be	O
+the	O
+result	O
+of	O
+the	O
+changing	O
+philosophies	O
+of	O
+care	O
+and	O
+management	O
+for	O
+the	O
+disabled	O
+,	O
+and	O
+a	O
+clearer	O
+understanding	O
+of	O
+the	O
+role	O
+of	O
+OT	O
+in	O
+the	O
+physical	O
+and	O
+mental	O
+well	O
+-	O
+being	O
+of	O
+the	O
+disabled	O
+[	O
+17	O
+]	O
+.	O
+
+In	O
+terms	O
+of	O
+actual	O
+shortages	O
+,	O
+some	O
+authors	O
+have	O
+reported	O
+ongoing	O
+vacancies	O
+and	O
+recruitment	O
+difficulties	O
+for	O
+OTs	O
+[	O
+11	O
+,	O
+18	O
+]	O
+while	O
+others	O
+have	O
+reported	O
+an	O
+increase	O
+in	O
+demand	O
+for	O
+both	O
+PTs	O
+[	O
+19	O
+]	O
+and	O
+OTs	O
+[	O
+20	O
+]	O
+.	O
+
+Speech	O
+language	O
+pathology	O
+is	O
+facing	O
+similar	O
+service	O
+demands	O
+.	O
+
+A	O
+report	O
+released	O
+in	O
+March	O
+2003	O
+by	O
+the	O
+College	O
+of	O
+Audiologists	O
+and	O
+Speech	O
+-	O
+Language	O
+Pathologists	O
+of	O
+Ontario	O
+(	O
+CASLPO	O
+)	O
+concluded	O
+that	O
+based	O
+on	O
+prevalence	O
+rates	O
+for	O
+Ontario	O
+residents	O
+with	O
+speech	O
+,	O
+language	O
+and	O
+related	O
+disorders	O
+,	O
+the	O
+demand	O
+for	O
+service	O
+would	O
+increase	O
+by	O
+13	O
+%	O
+while	O
+the	O
+number	O
+of	O
+SLPs	O
+would	O
+decrease	O
+by	O
+4	O
+%	O
+resulting	O
+in	O
+an	O
+overall	O
+reduction	O
+in	O
+service	O
+of	O
+15	O
+%	O
+[	O
+21	O
+]	O
+.	O
+
+The	O
+American	O
+Speech	O
+-	O
+Language	O
+-	O
+Hearing	O
+Association	O
+(	O
+ASHA	O
+)	O
+has	O
+been	O
+tracking	O
+SLP	O
+vacancies	O
+.	O
+
+In	O
+their	O
+2005	O
+ASHA	O
+Speech	O
+-	O
+Language	O
+Pathology	O
+Health	O
+Care	O
+survey	O
+,	O
+48	O
+%	O
+of	O
+respondents	O
+indicated	O
+that	O
+they	O
+had	O
+funded	O
+unfilled	O
+positions	O
+for	O
+SLPS	O
+in	O
+their	O
+agency	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+same	O
+survey	O
+also	O
+reported	O
+that	O
+65	O
+%	O
+of	O
+respondents	O
+in	O
+home	O
+care	O
+indicated	O
+that	O
+job	O
+openings	O
+were	O
+more	O
+numerous	O
+than	O
+job	O
+seekers	O
+in	O
+their	O
+geographic	O
+area	O
+.	O
+
+While	O
+labour	O
+market	O
+demand	O
+and	O
+supply	O
+are	O
+influential	O
+factors	O
+on	O
+recruitment	O
+and	O
+retention	O
+decisions	O
+,	O
+the	O
+development	O
+of	O
+strategies	O
+requires	O
+an	O
+understanding	O
+of	O
+conceptual	O
+frameworks	O
+or	O
+theories	O
+to	O
+categorise	O
+and	O
+explain	O
+how	O
+other	O
+underlying	O
+factors	O
+impact	O
+health	O
+worker	O
+'	O
+s	O
+mobility	O
+.	O
+
+For	O
+example	O
+,	O
+Lehmann	O
+et	O
+al	O
+.	O
+'	O
+s	O
+model	O
+described	O
+that	O
+health	O
+worker	O
+'	O
+s	O
+decisions	O
+to	O
+accept	O
+and	O
+stay	O
+in	O
+remote	O
+areas	O
+in	O
+the	O
+public	O
+sector	O
+depends	O
+on	O
+two	O
+interrelated	O
+aspects	O
+:	O
+the	O
+impact	O
+of	O
+the	O
+different	O
+environments	O
+(	O
+i	O
+.	O
+e	O
+.	O
+individual	O
+,	O
+local	O
+,	O
+work	O
+,	O
+national	O
+and	O
+international	O
+)	O
+and	O
+the	O
+location	O
+of	O
+decision	O
+-	O
+makers	O
+(	O
+i	O
+.	O
+e	O
+.	O
+local	O
+government	O
+,	O
+Ministry	O
+of	O
+Health	O
+,	O
+HR	O
+directorate	O
+,	O
+public	O
+service	O
+and	O
+other	O
+ministries	O
+)	O
+[	O
+23	O
+]	O
+.	O
+
+Behavioural	O
+and	O
+social	O
+science	O
+theories	O
+,	O
+such	O
+as	O
+those	O
+explained	O
+by	O
+Tett	O
+and	O
+Meyer	O
+,	O
+found	O
+that	O
+job	O
+satisfaction	O
+and	O
+organizational	O
+commitment	O
+each	O
+contribute	O
+independently	O
+to	O
+the	O
+prediction	O
+of	O
+the	O
+intention	O
+to	O
+resign	O
+(	O
+turnover	O
+)	O
+,	O
+however	O
+job	O
+satisfaction	O
+was	O
+a	O
+stronger	O
+predictor	O
+than	O
+organizational	O
+commitment	O
+[	O
+24	O
+]	O
+.	O
+
+Based	O
+on	O
+this	O
+notion	O
+,	O
+considerable	O
+research	O
+has	O
+been	O
+devoted	O
+to	O
+identifying	O
+factors	O
+that	O
+affect	O
+job	O
+satisfaction	O
+among	O
+rehabilitation	O
+professionals	O
+.	O
+
+While	O
+there	O
+is	O
+no	O
+single	O
+,	O
+agreed	O
+upon	O
+model	O
+of	O
+job	O
+satisfaction	O
+,	O
+a	O
+variety	O
+of	O
+theoretical	O
+models	O
+have	O
+been	O
+studied	O
+to	O
+explain	O
+concepts	O
+and	O
+relationships	O
+associated	O
+with	O
+overall	O
+job	O
+satisfaction	O
+.	O
+
+The	O
+two	O
+most	O
+commonly	O
+used	O
+theories	O
+of	O
+job	O
+satisfaction	O
+for	O
+rehabilitation	O
+professionals	O
+are	O
+the	O
+Herzberg	O
+'	O
+s	O
+Motivation	O
+-	O
+Hygiene	O
+Theory	O
+[	O
+25	O
+]	O
+and	O
+Mottaz	O
+'	O
+s	O
+concepts	O
+of	O
+work	O
+values	O
+and	O
+work	O
+rewards	O
+[	O
+26	O
+]	O
+.	O
+
+A	O
+number	O
+of	O
+rehabilitation	O
+studies	O
+have	O
+used	O
+the	O
+Herzberg	O
+'	O
+s	O
+Motivation	O
+-	O
+Hygiene	O
+Theory	O
+,	O
+also	O
+known	O
+as	O
+the	O
+two	O
+-	O
+factor	O
+theory	O
+of	O
+motivation	O
+to	O
+explain	O
+associations	O
+between	O
+motivation	O
+,	O
+job	O
+satisfaction	O
+and	O
+retention	O
+factors	O
+among	O
+OTs	O
+,	O
+PTs	O
+and	O
+SLPs	O
+[	O
+27	O
+-	O
+31	O
+]	O
+.	O
+
+Frederick	O
+Herzberg	O
+et	O
+al	O
+.	O
+explained	O
+that	O
+there	O
+were	O
+two	O
+independent	O
+incidents	O
+occurring	O
+at	O
+peoples	B
+'	O
+jobs	O
+:	O
+one	O
+that	O
+made	O
+them	O
+feel	O
+good	O
+or	O
+satisfied	O
+,	O
+and	O
+another	O
+that	O
+made	O
+them	O
+feel	O
+bad	O
+or	O
+dissatisfied	O
+at	O
+work	O
+[	O
+25	O
+]	O
+.	O
+
+Intrinsic	O
+factors	O
+that	O
+motivate	O
+people	B
+such	O
+as	O
+achievement	O
+,	O
+recognition	O
+,	O
+work	O
+itself	O
+,	O
+responsibility	O
+,	O
+advancement	O
+and	O
+personal	O
+growth	O
+were	O
+called	O
+the	O
+"	O
+motivators	O
+"	O
+which	O
+lead	O
+to	O
+feelings	O
+of	O
+satisfaction	O
+.	O
+
+Extrinsic	O
+factors	O
+such	O
+as	O
+work	O
+conditions	O
+,	O
+company	O
+policies	O
+,	O
+supervision	O
+,	O
+interpersonal	O
+work	O
+relations	O
+,	O
+salary	O
+and	O
+job	O
+security	O
+,	O
+known	O
+as	O
+"	O
+hygiene	O
+"	O
+factors	O
+,	O
+were	O
+claimed	O
+to	O
+prevent	O
+dissatisfaction	O
+.	O
+
+"	O
+Motivators	O
+"	O
+directly	O
+affect	O
+a	O
+person	B
+'	O
+s	O
+motivational	O
+drive	O
+to	O
+do	O
+a	O
+good	O
+job	O
+,	O
+therefore	O
+they	O
+are	O
+believed	O
+to	O
+be	O
+more	O
+important	O
+than	O
+hygiene	O
+factors	O
+.	O
+
+Mottaz	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+accounted	O
+for	O
+individual	O
+differences	O
+in	O
+job	O
+satisfaction	O
+among	O
+workers	O
+and	O
+based	O
+his	O
+study	O
+on	O
+two	O
+dimensions	O
+:	O
+"	O
+work	O
+rewards	O
+"	O
+and	O
+"	O
+work	O
+values	O
+"	O
+[	O
+26	O
+]	O
+.	O
+
+"	O
+Work	O
+rewards	O
+"	O
+are	O
+perceived	O
+characteristics	O
+of	O
+the	O
+job	O
+and	O
+have	O
+three	O
+conceptual	O
+clusters	O
+which	O
+include	O
+task	O
+,	O
+social	O
+and	O
+organizational	O
+rewards	O
+[	O
+26	O
+]	O
+.	O
+
+Mottaz	O
+describes	O
+"	O
+task	O
+rewards	O
+"	O
+(	O
+intrinsic	O
+)	O
+as	O
+having	O
+five	O
+independent	O
+characteristics	O
+including	O
+:	O
+skill	O
+variety	O
+,	O
+task	O
+identity	O
+,	O
+task	O
+significance	O
+,	O
+autonomy	O
+and	O
+feedback	O
+.	O
+
+Examples	O
+include	O
+interesting	O
+and	O
+challenging	O
+work	O
+,	O
+self	O
+-	O
+direction	O
+and	O
+responsibility	O
+,	O
+creativity	O
+,	O
+opportunities	O
+to	O
+use	O
+one	O
+'	O
+s	O
+skills	O
+and	O
+feedback	O
+.	O
+
+In	O
+the	O
+same	O
+study	O
+,	O
+Mottaz	O
+stated	O
+that	O
+"	O
+social	O
+rewards	O
+"	O
+(	O
+extrinsic	O
+)	O
+are	O
+derived	O
+from	O
+the	O
+interpersonal	O
+relationships	O
+established	O
+with	O
+others	O
+at	O
+work	O
+.	O
+
+Having	O
+supportive	O
+colleagues	O
+and	O
+supervisors	O
+is	O
+an	O
+example	O
+of	O
+this	O
+dimension	O
+.	O
+
+Lastly	O
+,	O
+"	O
+organizational	O
+rewards	O
+"	O
+(	O
+extrinsic	O
+)	O
+are	O
+tangible	O
+rewards	O
+that	O
+are	O
+provided	O
+by	O
+the	O
+employer	O
+/	O
+organization	O
+to	O
+facilitate	O
+performance	O
+.	O
+
+Such	O
+factors	O
+include	O
+working	O
+conditions	O
+,	O
+pay	O
+and	O
+fringe	O
+benefits	O
+,	O
+career	O
+advancement	O
+and	O
+security	O
+.	O
+
+The	O
+second	O
+dimension	O
+of	O
+job	O
+satisfaction	O
+is	O
+based	O
+on	O
+"	O
+work	O
+values	O
+"	O
+,	O
+which	O
+is	O
+the	O
+importance	O
+that	O
+individuals	O
+place	O
+on	O
+their	O
+work	O
+rewards	O
+[	O
+26	O
+]	O
+.	O
+
+For	O
+example	O
+,	O
+some	O
+rehabilitation	O
+therapists	O
+may	O
+value	O
+extrinsic	O
+rewards	O
+such	O
+as	O
+pay	O
+and	O
+benefits	O
+as	O
+more	O
+important	O
+than	O
+intrinsic	O
+factors	O
+like	O
+clinical	O
+autonomy	O
+and	O
+challenging	O
+work	O
+.	O
+
+Although	O
+the	O
+Herzberg	O
+and	O
+Mottaz	O
+conceptual	O
+frameworks	O
+are	O
+organized	O
+differently	O
+,	O
+their	O
+job	O
+satisfaction	O
+variables	O
+are	O
+very	O
+similar	O
+(	O
+i	O
+.	O
+e	O
+.	O
+work	O
+conditions	O
+,	O
+pay	O
+,	O
+interpersonal	O
+relationships	O
+,	O
+etc	O
+.	O
+)	O
+and	O
+they	O
+both	O
+classify	O
+these	O
+factors	O
+as	O
+having	O
+intrinsic	O
+or	O
+extrinsic	O
+elements	O
+.	O
+
+Despite	O
+the	O
+growing	O
+body	O
+of	O
+literature	O
+on	O
+recruitment	O
+and	O
+retention	O
+factors	O
+in	O
+various	O
+industries	O
+,	O
+there	O
+is	O
+a	O
+minimal	O
+amount	O
+of	O
+research	O
+studying	O
+these	O
+factors	O
+specifically	O
+among	O
+rehabilitation	O
+professionals	O
+.	O
+
+One	O
+published	O
+study	O
+however	O
+,	O
+did	O
+look	O
+at	O
+extrinsic	O
+and	O
+intrinsic	O
+job	O
+satisfaction	O
+factors	O
+on	O
+recruitment	O
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+retention	O
+of	O
+rehabilitation	O
+professionals	O
+(	O
+OTs	O
+,	O
+PTs	O
+and	O
+SLPs	O
+)	O
+[	O
+32	O
+]	O
+.	O
+
+Results	O
+from	O
+this	O
+study	O
+showed	O
+that	O
+intrinsic	O
+factors	O
+such	O
+as	O
+professional	O
+growth	O
+and	O
+having	O
+a	O
+work	O
+environment	O
+in	O
+line	O
+with	O
+personal	O
+values	O
+are	O
+more	O
+significant	O
+in	O
+predicting	O
+career	O
+satisfaction	O
+than	O
+extrinsic	O
+factors	O
+such	O
+as	O
+pay	O
+and	O
+continuing	O
+education	O
+.	O
+
+These	O
+same	O
+intrinsic	O
+factors	O
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+significant	O
+in	O
+predicting	O
+retention	O
+in	O
+rehabilitation	O
+professionals	O
+.	O
+
+Another	O
+study	O
+looking	O
+at	O
+recruitment	O
+and	O
+retention	O
+of	O
+allied	O
+health	O
+professionals	O
+in	O
+the	O
+rural	O
+areas	O
+in	O
+New	O
+South	O
+Wales	O
+identified	O
+that	O
+the	O
+main	O
+reasons	O
+why	O
+people	B
+liked	O
+working	O
+in	O
+rural	O
+areas	O
+were	O
+because	O
+of	O
+the	O
+attractive	O
+environment	O
+and	O
+helpful	O
+team	O
+members	O
+[	O
+33	O
+]	O
+.	O
+
+However	O
+82	O
+%	O
+of	O
+employees	O
+reported	O
+that	O
+having	O
+their	O
+partner	O
+move	O
+away	O
+was	O
+the	O
+number	O
+one	O
+reason	O
+for	O
+leaving	O
+a	O
+rural	O
+job	O
+.	O
+
+A	O
+similar	O
+study	O
+was	O
+conducted	O
+among	O
+OTs	O
+and	O
+PTs	O
+in	O
+Northwestern	O
+Ontario	O
+[	O
+34	O
+]	O
+.	O
+
+Findings	O
+from	O
+this	O
+study	O
+indicated	O
+that	O
+factors	O
+contributing	O
+to	O
+initial	O
+decision	O
+on	O
+location	O
+of	O
+practice	O
+include	O
+availability	O
+of	O
+leisure	O
+/	O
+recreation	O
+activities	O
+,	O
+proximity	O
+of	O
+family	O
+origin	O
+and	O
+influences	O
+of	O
+spouse	O
+/	O
+partners	O
+.	O
+
+Study	O
+results	O
+also	O
+showed	O
+that	O
+the	O
+main	O
+reasons	O
+therapists	O
+left	O
+their	O
+job	O
+were	O
+to	O
+be	O
+closer	O
+to	O
+their	O
+family	O
+,	O
+lack	O
+of	O
+job	O
+opportunity	O
+and	O
+spousal	O
+influence	O
+.	O
+
+Solely	O
+understanding	O
+factors	O
+that	O
+influence	O
+recruitment	O
+and	O
+retention	O
+decisions	O
+is	O
+not	O
+sufficient	O
+in	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
+for	O
+rehabilitation	O
+professionals	O
+.	O
+
+In	O
+order	O
+for	O
+the	O
+plan	O
+to	O
+be	O
+effective	O
+and	O
+sustainable	O
+in	O
+addressing	O
+these	O
+factors	O
+,	O
+the	O
+most	O
+important	O
+and	O
+feasible	O
+workforce	O
+strategies	O
+needs	O
+to	O
+be	O
+identified	O
+.	O
+
+There	O
+have	O
+been	O
+a	O
+number	O
+of	O
+reports	O
+on	O
+health	O
+human	B
+resources	O
+(	O
+HHR	O
+)	O
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+,	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+for	O
+physicians	O
+[	O
+35	O
+,	O
+36	O
+]	O
+and	O
+nurses	O
+[	O
+37	O
+]	O
+,	O
+however	O
+information	O
+regarding	O
+rehabilitation	O
+professionals	O
+is	O
+lacking	O
+.	O
+
+Canadian	O
+reports	O
+indicate	O
+that	O
+the	O
+main	O
+reason	O
+for	O
+significant	O
+gaps	O
+in	O
+this	O
+field	O
+is	O
+the	O
+absence	O
+of	O
+current	O
+and	O
+reliable	O
+data	O
+available	O
+on	O
+supply	O
+,	O
+demand	O
+and	O
+labour	O
+force	O
+participation	O
+trends	O
+for	O
+rehabilitation	O
+therapists	O
+[	O
+38	O
+-	O
+40	O
+]	O
+.	O
+
+There	O
+is	O
+some	O
+research	O
+that	O
+has	O
+investigated	O
+theoretical	O
+models	O
+of	O
+job	O
+satisfaction	O
+on	O
+recruitment	O
+and	O
+retention	O
+[	O
+28	O
+,	O
+32	O
+]	O
+;	O
+however	O
+few	O
+studies	O
+have	O
+looked	O
+at	O
+how	O
+these	O
+models	O
+have	O
+been	O
+implemented	O
+.	O
+
+Other	O
+studies	O
+have	O
+examined	O
+the	O
+relationship	O
+of	O
+gender	O
+,	O
+workplace	O
+setting	O
+(	O
+i	O
+.	O
+e	O
+.	O
+hospital	O
+,	O
+ambulatory	O
+,	O
+rehabilitation	O
+,	O
+acute	O
+and	O
+long	O
+-	O
+term	O
+care	O
+)	O
+and	O
+geographical	O
+location	O
+(	O
+i	O
+.	O
+e	O
+.	O
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+or	O
+urban	O
+)	O
+on	O
+job	O
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+retention	O
+among	O
+rehabilitation	O
+professionals	O
+[	O
+41	O
+-	O
+43	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+no	O
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+studies	O
+have	O
+examined	O
+conceptual	O
+frameworks	O
+for	O
+organizing	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+for	O
+rehabilitation	O
+therapists	O
+.	O
+
+To	O
+address	O
+this	O
+gap	O
+,	O
+this	O
+research	O
+identified	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+from	O
+the	O
+literature	O
+for	O
+rehabilitation	O
+professionals	O
+and	O
+determined	O
+their	O
+importance	O
+and	O
+feasibility	O
+using	O
+expert	O
+panels	O
+.	O
+
+Methods	O
+
+Phase	O
+1	O
+:	O
+Literature	O
+Review	O
+
+Identification	O
+of	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+
+A	O
+review	O
+of	O
+the	O
+literature	O
+was	O
+conducted	O
+to	O
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+recruitment	O
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+retention	O
+strategies	O
+for	O
+rehabilitation	O
+therapists	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+rehabilitation	O
+professionals	O
+were	O
+defined	O
+as	O
+physical	O
+therapists	O
+(	O
+PTs	O
+)	O
+,	O
+occupational	O
+therapists	O
+(	O
+OTs	O
+)	O
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+speech	O
+-	O
+language	O
+pathologists	O
+(	O
+SLPs	O
+)	O
+.	O
+
+Both	O
+published	O
+and	O
+non	O
+-	O
+empirical	O
+literature	O
+was	O
+accessed	O
+in	O
+this	O
+review	O
+.	O
+
+Keywords	O
+used	O
+to	O
+search	O
+for	O
+relevant	O
+published	O
+studies	O
+in	O
+the	O
+Consolidated	O
+International	O
+Nursing	O
+and	O
+Allied	O
+Health	O
+Sciences	O
+Library	O
+(	O
+CINAHL	O
+)	O
+(	O
+1982	O
+to	O
+2005	O
+)	O
+and	O
+Medline	O
+(	O
+1996	O
+to	O
+2005	O
+)	O
+included	O
+:	O
+"	O
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+resources	O
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+"	O
+,	O
+"	O
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+vocational	O
+"	O
+,	O
+"	O
+allied	O
+health	O
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+or	O
+personnel	O
+"	O
+,	O
+"	O
+recruitment	O
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+"	O
+,	O
+"	O
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+"	O
+,	O
+"	O
+physical	O
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+or	O
+physiotherapist	O
+"	O
+,	O
+"	O
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+therapy	O
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+occupational	O
+therapist	O
+"	O
+,	O
+"	O
+speech	O
+-	O
+language	O
+pathologist	O
+or	O
+speech	O
+-	O
+language	O
+pathology	O
+"	O
+.	O
+
+Non	O
+-	O
+empirical	O
+literature	O
+searches	O
+were	O
+made	O
+on	O
+international	O
+and	O
+national	O
+on	O
+-	O
+line	O
+catalogues	O
+and	O
+publications	O
+from	O
+health	O
+organizations	O
+,	O
+professional	O
+associations	O
+,	O
+and	O
+hospital	O
+and	O
+home	O
+care	O
+organizations	O
+.	O
+
+International	O
+reports	O
+were	O
+limited	O
+to	O
+developed	O
+countries	O
+since	O
+the	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+identify	O
+strategies	O
+appropriate	O
+to	O
+the	O
+Ontario	O
+setting	O
+.	O
+
+Organization	O
+and	O
+consolidation	O
+of	O
+strategies	O
+
+There	O
+was	O
+a	O
+paucity	O
+of	O
+peer	O
+-	O
+reviewed	O
+studies	O
+obtained	O
+exploring	O
+rehabilitation	O
+HHR	O
+strategies	O
+,	O
+therefore	O
+the	O
+majority	O
+of	O
+strategies	O
+were	O
+selected	O
+from	O
+grey	O
+literature	O
+reports	O
+from	O
+international	O
+,	O
+national	O
+and	O
+provincial	O
+health	O
+organizations	O
+.	O
+
+From	O
+the	O
+literature	O
+review	O
+,	O
+107	O
+potential	O
+strategies	O
+were	O
+identified	O
+according	O
+to	O
+their	O
+relevance	O
+to	O
+HHR	O
+issues	O
+for	O
+rehabilitation	O
+in	O
+Ontario	O
+.	O
+
+These	O
+strategies	O
+were	O
+then	O
+categorized	O
+into	O
+two	O
+broad	O
+groups	O
+:	O
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+)	O
+Recruitment	O
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+Retention	O
+(	O
+n	O
+=	O
+73	O
+)	O
+,	O
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+B	O
+)	O
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+(	O
+n	O
+=	O
+34	O
+)	O
+.	O
+
+The	O
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+to	O
+rehabilitation	O
+professionals	O
+and	O
+they	O
+were	O
+reviewed	O
+by	O
+a	O
+group	O
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+three	O
+individuals	O
+collectively	O
+(	O
+rehabilitation	O
+researcher	O
+,	O
+manager	O
+,	O
+and	O
+clinician	O
+)	O
+for	O
+duplication	O
+,	O
+clarity	O
+,	O
+action	O
+focused	O
+properties	O
+and	O
+appropriateness	O
+to	O
+the	O
+Canadian	O
+or	O
+Ontario	O
+setting	O
+.	O
+
+When	O
+necessary	O
+,	O
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+small	O
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+-	O
+worded	O
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+a	O
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+.	O
+
+This	O
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+in	O
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+of	O
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+Recruitment	O
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+Retention	O
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+24	O
+Education	O
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+.	O
+
+Only	O
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+six	O
+education	O
+strategies	O
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+from	O
+peer	O
+-	O
+reviewed	O
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+.	O
+
+Since	O
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+,	O
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+-	O
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+conceptual	O
+framework	O
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+the	O
+breadth	O
+of	O
+the	O
+strategies	O
+obtained	O
+from	O
+the	O
+literature	O
+review	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
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+Services	O
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+.	O
+
+Each	O
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+(	O
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+)	O
+.	O
+
+The	O
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+were	O
+:	O
+(	O
+1	O
+)	O
+Quality	O
+of	O
+Worklife	O
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+[	O
+n	O
+=	O
+19	O
+]	O
+;	O
+(	O
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+)	O
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+Skill	O
+Mix	O
+[	O
+n	O
+=	O
+6	O
+]	O
+;	O
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+(	O
+3	O
+)	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+[	O
+n	O
+=	O
+15	O
+]	O
+.	O
+
+The	O
+two	O
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+(	O
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+)	O
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+Training	O
+[	O
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+=	O
+11	O
+]	O
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+(	O
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+)	O
+Professional	O
+Development	O
+(	O
+n	O
+=	O
+13	O
+)	O
+.	O
+
+Phase	O
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+Panel	O
+
+Participant	B
+Selection	O
+
+Once	O
+this	O
+study	O
+was	O
+approved	O
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+Research	O
+Ethics	O
+Board	O
+at	O
+the	O
+University	O
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+Toronto	O
+,	O
+key	O
+informants	O
+who	O
+participated	O
+in	O
+a	O
+previous	O
+study	O
+regarding	O
+rehabilitation	O
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+and	O
+demand	O
+at	O
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+University	O
+of	O
+Toronto	O
+[	O
+21	O
+]	O
+were	O
+asked	O
+to	O
+nominate	O
+potential	O
+participants	B
+for	O
+the	O
+panels	O
+.	O
+
+The	O
+selection	O
+criteria	O
+considered	O
+were	O
+acknowledged	O
+leadership	O
+in	O
+the	O
+panel	O
+member	O
+'	O
+s	O
+specialty	O
+,	O
+expertise	O
+in	O
+recruitment	O
+and	O
+retention	O
+or	O
+education	O
+and	O
+training	O
+of	O
+rehabilitation	O
+professionals	O
+.	O
+
+Absence	O
+of	O
+conflicts	O
+of	O
+interest	O
+,	O
+geographic	O
+diversity	O
+,	O
+and	O
+diversity	O
+of	O
+practice	O
+setting	O
+were	O
+also	O
+considered	O
+.	O
+
+After	O
+purposefully	O
+selecting	O
+the	O
+initial	O
+list	O
+of	O
+candidates	O
+from	O
+among	O
+the	O
+nominations	O
+,	O
+each	O
+nominee	O
+was	O
+contacted	O
+to	O
+establish	O
+their	O
+interest	O
+and	O
+availability	O
+.	O
+
+Those	O
+who	O
+expressed	O
+an	O
+interest	O
+in	O
+participating	O
+were	O
+asked	O
+to	O
+send	O
+their	O
+curriculum	O
+vitae	O
+to	O
+help	O
+the	O
+research	O
+team	O
+evaluate	O
+their	O
+contributions	O
+to	O
+their	O
+field	O
+of	O
+expertise	O
+.	O
+
+Once	O
+candidate	O
+panelists	O
+were	O
+selected	O
+,	O
+each	O
+received	O
+a	O
+letter	O
+explaining	O
+the	O
+expert	O
+panel	O
+process	O
+and	O
+consent	O
+form	O
+.	O
+
+Two	O
+separate	O
+panels	O
+were	O
+constructed	O
+:	O
+one	O
+for	O
+Recruitment	O
+and	O
+Retention	O
+(	O
+n	O
+=	O
+8	O
+)	O
+and	O
+the	O
+other	O
+for	O
+Education	O
+(	O
+n	O
+=	O
+9	O
+)	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+The	O
+size	O
+of	O
+the	O
+panel	O
+was	O
+large	O
+enough	O
+to	O
+permit	O
+diversity	O
+of	O
+representation	O
+while	O
+still	O
+being	O
+small	O
+enough	O
+to	O
+allow	O
+all	O
+participants	B
+to	O
+be	O
+involved	O
+in	O
+the	O
+group	O
+discussion	O
+[	O
+45	O
+]	O
+.	O
+
+Expert	O
+Panel	O
+Process	O
+:	O
+Round	O
+1	O
+Survey	O
+
+A	O
+modified	O
+-	O
+delphi	O
+technique	O
+was	O
+then	O
+used	O
+for	O
+the	O
+expert	O
+panel	O
+process	O
+,	O
+[	O
+46	O
+,	O
+47	O
+]	O
+based	O
+on	O
+the	O
+RAND	O
+/	O
+UCLA	O
+appropriateness	O
+method	O
+[	O
+45	O
+]	O
+.	O
+
+In	O
+round	O
+1	O
+,	O
+members	O
+of	O
+the	O
+Recruitment	O
+and	O
+Retention	O
+panel	O
+were	O
+sent	O
+an	O
+electronic	O
+survey	O
+containing	O
+the	O
+40	O
+strategies	O
+identified	O
+from	O
+the	O
+literature	O
+review	O
+and	O
+the	O
+Education	O
+panelists	O
+were	O
+also	O
+sent	O
+an	O
+electronic	O
+survey	O
+with	O
+24	O
+strategies	O
+.	O
+
+For	O
+Round	O
+1	O
+,	O
+each	O
+panel	O
+was	O
+asked	O
+to	O
+rate	O
+the	O
+strategies	O
+using	O
+a	O
+nine	O
+-	O
+point	O
+Likert	O
+-	O
+type	O
+rating	O
+scale	O
+that	O
+ranged	O
+from	O
+"	O
+none	O
+"	O
+(	O
+1	O
+)	O
+to	O
+"	O
+maximum	O
+"	O
+(	O
+9	O
+)	O
+,	O
+on	O
+two	O
+key	O
+dimensions	O
+:	O
+Feasibility	O
+and	O
+Importance	O
+.	O
+
+Feasibility	O
+was	O
+defined	O
+as	O
+the	O
+practicality	O
+and	O
+cost	O
+implications	O
+of	O
+the	O
+strategy	O
+and	O
+was	O
+rated	O
+from	O
+the	O
+respondents	O
+'	O
+perspective	O
+.	O
+
+Importance	O
+was	O
+defined	O
+as	O
+how	O
+valuable	O
+,	O
+appropriate	O
+and	O
+useful	O
+the	O
+strategy	O
+could	O
+be	O
+for	O
+rehabilitation	O
+HHR	O
+planning	O
+in	O
+Ontario	O
+.	O
+
+At	O
+the	O
+end	O
+of	O
+the	O
+survey	O
+,	O
+panelists	O
+were	O
+given	O
+the	O
+opportunity	O
+to	O
+suggest	O
+additional	O
+strategies	O
+that	O
+they	O
+felt	O
+were	O
+appropriate	O
+to	O
+consider	O
+.	O
+
+Once	O
+completed	O
+,	O
+panelists	O
+were	O
+asked	O
+to	O
+return	O
+the	O
+survey	O
+to	O
+the	O
+study	O
+office	O
+by	O
+email	O
+or	O
+fax	O
+prior	O
+to	O
+the	O
+expert	O
+panel	O
+meeting	O
+in	O
+Round	O
+2	O
+.	O
+
+Data	O
+from	O
+each	O
+questionnaire	O
+were	O
+entered	O
+into	O
+a	O
+spreadsheet	O
+and	O
+tabulated	O
+.	O
+
+Descriptive	O
+statistics	O
+were	O
+calculated	O
+for	O
+each	O
+strategy	O
+using	O
+frequency	O
+distributions	O
+and	O
+proportional	O
+percentages	O
+of	O
+respondents	O
+.	O
+
+Importance	O
+and	O
+feasibility	O
+rankings	O
+were	O
+based	O
+on	O
+the	O
+percentage	O
+of	O
+expert	O
+panelists	O
+'	O
+low	O
+,	O
+medium	O
+and	O
+high	O
+ratings	O
+.	O
+
+Expert	O
+Panel	O
+Process	O
+Round	O
+2	O
+:	O
+Expert	O
+Panel	O
+one	O
+-	O
+day	O
+meeting	O
+
+After	O
+the	O
+independent	O
+completion	O
+of	O
+the	O
+survey	O
+,	O
+each	O
+panel	O
+was	O
+convened	O
+separately	O
+for	O
+a	O
+one	O
+-	O
+day	O
+meeting	O
+for	O
+final	O
+discussions	O
+,	O
+debates	O
+and	O
+consensus	O
+voting	O
+to	O
+decide	O
+on	O
+strategies	O
+[	O
+48	O
+]	O
+.	O
+
+A	O
+strategy	O
+that	O
+had	O
+been	O
+scored	O
+7	O
+,	O
+8	O
+or	O
+9	O
+for	O
+both	O
+feasibility	O
+and	O
+importance	O
+by	O
+two	O
+-	O
+thirds	O
+of	O
+the	O
+panel	O
+was	O
+considered	O
+a	O
+high	O
+rating	O
+.	O
+
+Strategies	O
+that	O
+had	O
+a	O
+combination	O
+of	O
+medium	O
+and	O
+high	O
+scores	O
+between	O
+4	O
+and	O
+9	O
+in	O
+either	O
+of	O
+the	O
+two	O
+dimensions	O
+were	O
+considered	O
+medium	O
+rated	O
+strategies	O
+,	O
+while	O
+low	O
+rated	O
+strategies	O
+had	O
+scores	O
+between	O
+1	O
+and	O
+3	O
+for	O
+both	O
+dimensions	O
+.	O
+
+On	O
+the	O
+day	O
+of	O
+the	O
+meeting	O
+,	O
+the	O
+panelists	O
+were	O
+given	O
+a	O
+copy	O
+of	O
+the	O
+aggregated	O
+survey	O
+results	O
+indicating	O
+the	O
+ratings	O
+of	O
+all	O
+of	O
+the	O
+strategies	O
+.	O
+
+High	O
+and	O
+low	O
+rated	O
+strategies	O
+were	O
+not	O
+discussed	O
+as	O
+there	O
+was	O
+already	O
+consensus	O
+,	O
+whereas	O
+all	O
+medium	O
+rated	O
+strategies	O
+were	O
+subject	O
+to	O
+discussion	O
+.	O
+
+Using	O
+a	O
+nominal	O
+group	O
+process	O
+[	O
+47	O
+]	O
+,	O
+each	O
+strategy	O
+was	O
+discussed	O
+in	O
+turn	O
+,	O
+and	O
+panelists	O
+were	O
+given	O
+an	O
+opportunity	O
+to	O
+raise	O
+any	O
+issues	O
+or	O
+concerns	O
+regarding	O
+the	O
+clarity	O
+and	O
+wording	O
+of	O
+each	O
+strategy	O
+.	O
+
+Each	O
+of	O
+the	O
+strategies	O
+discussed	O
+were	O
+then	O
+individually	O
+rated	O
+a	O
+second	O
+time	O
+by	O
+each	O
+panelist	O
+in	O
+an	O
+attempt	O
+to	O
+reach	O
+further	O
+consensus	O
+.	O
+
+Results	O
+
+Selection	O
+of	O
+strategies	O
+for	O
+Round	O
+1	O
+:	O
+Modified	O
+Delphi	O
+process	O
+
+Following	O
+Round	O
+1	O
+rating	O
+of	O
+the	O
+40	O
+identified	O
+strategies	O
+,	O
+the	O
+Recruitment	O
+and	O
+Retention	O
+panel	O
+reached	O
+consensus	O
+on	O
+12	O
+strategies	O
+.	O
+
+However	O
+,	O
+14	O
+had	O
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+combination	O
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+high	O
+/	O
+medium	O
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+feasibility	O
+ratings	O
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+14	O
+had	O
+medium	O
+ratings	O
+on	O
+both	O
+dimensions	O
+,	O
+therefore	O
+it	O
+required	O
+further	O
+discussion	O
+.	O
+
+An	O
+additional	O
+strategy	O
+regarding	O
+family	O
+relocation	O
+programs	O
+was	O
+added	O
+by	O
+this	O
+panel	O
+.	O
+
+The	O
+Education	O
+Panel	O
+ranked	O
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+high	O
+importance	O
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+feasibility	O
+after	O
+Round	O
+1	O
+.	O
+
+Since	O
+there	O
+were	O
+only	O
+eight	O
+strategies	O
+with	O
+medium	O
+ratings	O
+,	O
+this	O
+expert	O
+panel	O
+decided	O
+to	O
+review	O
+all	O
+the	O
+strategies	O
+at	O
+the	O
+face	O
+-	O
+to	O
+-	O
+face	O
+meeting	O
+to	O
+discuss	O
+the	O
+rationale	O
+that	O
+would	O
+explain	O
+why	O
+some	O
+of	O
+the	O
+highly	O
+rated	O
+strategies	O
+were	O
+not	O
+already	O
+implemented	O
+and	O
+to	O
+come	O
+to	O
+a	O
+consensus	O
+on	O
+the	O
+other	O
+eight	O
+medium	O
+rated	O
+strategies	O
+.	O
+
+They	O
+also	O
+added	O
+an	O
+additional	O
+strategy	O
+for	O
+career	O
+paths	O
+.	O
+
+Selection	O
+of	O
+strategies	O
+for	O
+Round	O
+2	O
+:	O
+Face	O
+-	O
+to	O
+-	O
+face	O
+meeting	O
+
+A	O
+total	O
+of	O
+34	O
+strategies	O
+were	O
+identified	O
+by	O
+both	O
+the	O
+Recruitment	O
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+Retention	O
+and	O
+Education	O
+expert	O
+panels	O
+as	O
+being	O
+important	O
+and	O
+feasible	O
+for	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
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+recruitment	O
+and	O
+retention	O
+of	O
+rehabilitation	O
+professionals	O
+.	O
+
+Under	O
+the	O
+Recruitment	O
+and	O
+Retention	O
+theme	O
+,	O
+seven	O
+were	O
+categorized	O
+as	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+;	O
+two	O
+were	O
+Workload	O
+and	O
+Skill	O
+Mix	O
+,	O
+and	O
+another	O
+seven	O
+were	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+.	O
+
+As	O
+for	O
+the	O
+Education	O
+panel	O
+,	O
+five	O
+were	O
+categorized	O
+as	O
+Education	O
+and	O
+Training	O
+strategies	O
+while	O
+the	O
+other	O
+thirteen	O
+were	O
+related	O
+to	O
+Professional	O
+Development	O
+.	O
+
+As	O
+indicated	O
+in	O
+Table	O
+2	O
+,	O
+at	O
+the	O
+end	O
+of	O
+the	O
+second	O
+round	O
+of	O
+voting	O
+,	O
+the	O
+Recruitment	O
+and	O
+Retention	O
+panel	O
+had	O
+a	O
+total	O
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+strategies	O
+,	O
+8	O
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+/	O
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+,	O
+8	O
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+9	O
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+ratings	O
+for	O
+both	O
+dimensions	O
+.	O
+
+The	O
+Education	O
+panel	O
+on	O
+the	O
+other	O
+hand	O
+had	O
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+total	O
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+18	O
+high	O
+,	O
+1	O
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+/	O
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+,	O
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+.	O
+
+Recruitment	O
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+Retention	O
+Strategy	O
+Rankings	O
+
+Table	O
+3	O
+provides	O
+a	O
+detailed	O
+description	O
+and	O
+ranking	O
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+each	O
+of	O
+the	O
+recruitment	O
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+retention	O
+strategies	O
+that	O
+were	O
+rated	O
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+and	O
+feasible	O
+.	O
+
+The	O
+importance	O
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+feasibility	O
+rankings	O
+were	O
+based	O
+on	O
+the	O
+largest	O
+proportion	O
+of	O
+panel	O
+members	O
+rating	O
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+strategy	O
+a	O
+7	O
+,	O
+8	O
+or	O
+9	O
+.	O
+
+The	O
+overall	O
+combined	O
+ranking	O
+was	O
+based	O
+on	O
+the	O
+average	O
+of	O
+the	O
+proportion	O
+of	O
+these	O
+two	O
+dimensions	O
+.	O
+
+Among	O
+these	O
+selected	O
+strategies	O
+,	O
+the	O
+majority	O
+were	O
+classified	O
+under	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+(	O
+44	O
+%	O
+)	O
+and	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+(	O
+44	O
+%	O
+)	O
+,	O
+followed	O
+by	O
+Workload	O
+and	O
+Skill	O
+Mix	O
+(	O
+12	O
+%	O
+)	O
+.	O
+
+It	O
+should	O
+be	O
+noted	O
+that	O
+some	O
+strategies	O
+had	O
+equal	O
+rankings	O
+;	O
+therefore	O
+the	O
+total	O
+number	O
+of	O
+rankings	O
+did	O
+not	O
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+the	O
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+number	O
+of	O
+strategies	O
+.	O
+
+Recruitment	O
+and	O
+retention	O
+strategies	O
+that	O
+had	O
+a	O
+combination	O
+of	O
+high	O
+and	O
+medium	O
+ratings	O
+in	O
+either	O
+of	O
+the	O
+two	O
+dimensions	O
+included	O
+:	O
+sense	O
+of	O
+empowerment	O
+in	O
+promoting	O
+healthy	O
+work	O
+environments	O
+;	O
+team	O
+-	O
+building	O
+exercises	O
+;	O
+developing	O
+participatory	O
+decision	O
+-	O
+making	O
+systems	O
+;	O
+improving	O
+rural	O
+working	O
+conditions	O
+;	O
+recognizing	O
+work	O
+-	O
+life	O
+balance	O
+;	O
+creating	O
+an	O
+environment	O
+where	O
+staff	O
+are	O
+valued	O
+;	O
+optimizing	O
+scope	O
+of	O
+practice	O
+and	O
+work	O
+-	O
+management	O
+autonomy	O
+.	O
+
+Strategies	O
+that	O
+had	O
+medium	O
+importance	O
+and	O
+feasibility	O
+ratings	O
+included	O
+:	O
+resolving	O
+concerns	O
+about	O
+liability	O
+and	O
+accountability	O
+in	O
+collaborative	O
+practice	O
+;	O
+recruiting	O
+international	O
+trained	O
+therapists	O
+;	O
+opportunity	O
+to	O
+work	O
+in	O
+different	O
+settings	O
+;	O
+interprofessional	O
+payment	O
+schemes	O
+;	O
+family	O
+leave	O
+;	O
+staff	O
+recognition	O
+and	O
+creating	O
+a	O
+position	O
+for	O
+a	O
+provincial	O
+health	O
+professional	O
+recruiter	O
+.	O
+
+Low	O
+importance	O
+and	O
+feasibility	O
+strategies	O
+included	O
+:	O
+word	O
+of	O
+mouth	O
+references	O
+;	O
+bursaries	O
+and	O
+retention	O
+bonuses	O
+;	O
+exchange	O
+employment	O
+opportunities	O
+;	O
+health	O
+promotion	O
+;	O
+retention	O
+workshop	O
+;	O
+80	O
+-	O
+20	O
+staffing	O
+model	O
+(	O
+80	O
+%	O
+clinical	O
+and	O
+20	O
+%	O
+learning	O
+new	O
+skills	O
+or	O
+training	O
+others	O
+)	O
+;	O
+using	O
+recruitment	O
+agencies	O
+and	O
+providing	O
+recruitment	O
+bonuses	O
+(	O
+Table	O
+4	O
+)	O
+.	O
+
+Education	O
+Strategy	O
+Rankings	O
+
+Education	O
+strategies	O
+that	O
+were	O
+rated	O
+highly	O
+important	O
+and	O
+feasible	O
+are	O
+described	O
+in	O
+Table	O
+5	O
+.	O
+
+The	O
+majority	O
+of	O
+strategies	O
+in	O
+this	O
+group	O
+tend	O
+to	O
+be	O
+in	O
+the	O
+area	O
+of	O
+Professional	O
+Development	O
+(	O
+72	O
+%	O
+)	O
+,	O
+more	O
+so	O
+than	O
+Education	O
+and	O
+Training	O
+(	O
+28	O
+%	O
+)	O
+.	O
+
+The	O
+medium	O
+rated	O
+education	O
+strategies	O
+included	O
+:	O
+expand	O
+interprofessional	O
+education	O
+;	O
+provide	O
+incentives	O
+for	O
+students	O
+interested	O
+in	O
+rural	O
+practice	O
+;	O
+summer	O
+mentorship	O
+programs	O
+for	O
+high	O
+school	O
+students	O
+;	O
+and	O
+aboriginal	O
+student	O
+support	O
+program	O
+.	O
+
+The	O
+strategies	O
+that	O
+were	O
+considered	O
+neither	O
+feasible	O
+nor	O
+important	O
+included	O
+:	O
+using	O
+return	O
+of	O
+service	O
+contracts	O
+after	O
+professional	O
+development	O
+;	O
+create	O
+a	O
+tiered	O
+pathway	O
+approach	O
+through	O
+modular	O
+education	O
+and	O
+laddered	O
+credentialing	O
+and	O
+in	O
+accreditation	O
+standards	O
+allow	O
+greater	O
+use	O
+of	O
+rural	O
+practice	O
+sites	O
+(	O
+Table	O
+6	O
+)	O
+.	O
+
+Since	O
+the	O
+purpose	O
+of	O
+the	O
+panel	O
+was	O
+to	O
+identify	O
+recruitment	O
+and	O
+retention	O
+and	O
+education	O
+strategies	O
+that	O
+could	O
+inform	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
+for	O
+rehabilitation	O
+professionals	O
+,	O
+there	O
+was	O
+also	O
+discussion	O
+about	O
+contextual	O
+factors	O
+that	O
+would	O
+influence	O
+a	O
+plan	O
+.	O
+
+Panelists	O
+commented	O
+that	O
+key	O
+factors	O
+to	O
+consider	O
+prior	O
+to	O
+implementation	O
+of	O
+these	O
+strategies	O
+should	O
+include	O
+workplace	O
+setting	O
+,	O
+geographical	O
+location	O
+(	O
+i	O
+.	O
+e	O
+.	O
+urban	O
+and	O
+rural	O
+)	O
+and	O
+gender	O
+issues	O
+.	O
+
+Discussion	O
+
+The	O
+purpose	O
+of	O
+this	O
+study	O
+was	O
+to	O
+identify	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+to	O
+inform	O
+the	O
+development	O
+of	O
+HHR	O
+planning	O
+for	O
+rehabilitation	O
+professionals	O
+in	O
+Ontario	O
+.	O
+
+This	O
+study	O
+highlights	O
+that	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+,	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+and	O
+Professional	O
+Development	O
+are	O
+the	O
+three	O
+major	O
+areas	O
+of	O
+focus	O
+when	O
+developing	O
+a	O
+competitive	O
+HR	O
+plan	O
+in	O
+the	O
+rehabilitation	O
+sector	O
+.	O
+
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+strategies	O
+ranked	O
+among	O
+the	O
+top	O
+category	O
+for	O
+recruitment	O
+and	O
+retention	O
+of	O
+rehabilitation	O
+therapists	O
+.	O
+
+This	O
+has	O
+also	O
+been	O
+found	O
+among	O
+nurses	O
+[	O
+44	O
+]	O
+where	O
+it	O
+was	O
+reported	O
+that	O
+addressing	O
+such	O
+factors	O
+can	O
+affect	O
+the	O
+overall	O
+success	O
+of	O
+the	O
+program	O
+[	O
+49	O
+]	O
+.	O
+
+Specifically	O
+,	O
+our	O
+findings	O
+showed	O
+that	O
+the	O
+top	O
+ranked	O
+strategy	O
+for	O
+both	O
+importance	O
+and	O
+feasibility	O
+was	O
+improving	O
+and	O
+maintaining	O
+the	O
+safety	O
+of	O
+rehabilitation	O
+professionals	O
+in	O
+the	O
+workplace	O
+.	O
+
+Specific	O
+strategies	O
+that	O
+could	O
+reduce	O
+aggression	O
+,	O
+abuse	O
+and	O
+violence	O
+in	O
+the	O
+workplace	O
+include	O
+:	O
+zero	O
+tolerance	O
+policies	O
+,	O
+access	O
+to	O
+employee	O
+support	O
+programs	O
+and	O
+providing	O
+assistance	O
+to	O
+rehabilitation	O
+professionals	O
+who	O
+work	O
+alone	O
+(	O
+i	O
+.	O
+e	O
+.	O
+home	O
+care	O
+and	O
+rural	O
+and	O
+remote	O
+areas	O
+)	O
+.	O
+
+Since	O
+there	O
+is	O
+less	O
+control	O
+over	O
+the	O
+environment	O
+in	O
+the	O
+home	O
+care	O
+setting	O
+,	O
+safety	O
+may	O
+become	O
+a	O
+greater	O
+concern	O
+in	O
+one	O
+practice	O
+setting	O
+over	O
+another	O
+.	O
+
+This	O
+might	O
+suggest	O
+that	O
+because	O
+there	O
+is	O
+less	O
+control	O
+in	O
+environments	O
+such	O
+as	O
+home	O
+care	O
+,	O
+remote	O
+areas	O
+,	O
+and	O
+psychiatric	O
+settings	O
+,	O
+maintaining	O
+safety	O
+will	O
+be	O
+more	O
+difficult	O
+and	O
+that	O
+solutions	O
+will	O
+need	O
+to	O
+be	O
+tailored	O
+to	O
+these	O
+settings	O
+in	O
+order	O
+to	O
+ensure	O
+retention	O
+of	O
+providers	O
+.	O
+
+Although	O
+no	O
+studies	O
+have	O
+looked	O
+at	O
+implementing	O
+personal	O
+safety	O
+strategies	O
+for	O
+home	O
+care	O
+therapists	O
+,	O
+written	O
+policies	O
+and	O
+procedures	O
+for	O
+home	O
+care	O
+nurses	O
+during	O
+inclement	O
+weather	O
+and	O
+for	O
+dealing	O
+with	O
+abusive	O
+or	O
+dangerous	O
+patients	B
+,	O
+families	O
+and	O
+neighbourhoods	O
+have	O
+been	O
+reported	O
+[	O
+50	O
+]	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+above	O
+,	O
+ensuring	O
+open	O
+and	O
+timely	O
+communication	O
+between	O
+employer	O
+and	O
+worker	O
+was	O
+also	O
+ranked	O
+highly	O
+among	O
+the	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+.	O
+
+Examples	O
+of	O
+strategies	O
+include	O
+:	O
+open	O
+door	O
+policies	O
+,	O
+employee	O
+advisory	O
+committees	O
+and	O
+regular	O
+staff	O
+meetings	O
+and	O
+evaluations	O
+.	O
+
+Although	O
+these	O
+strategies	O
+were	O
+reported	O
+to	O
+be	O
+used	O
+among	O
+organizations	O
+providing	O
+services	O
+to	O
+persons	B
+with	O
+developmental	O
+disabilities	O
+in	O
+Alberta	O
+,	O
+there	O
+was	O
+no	O
+description	O
+of	O
+the	O
+organizations	O
+,	O
+sample	O
+size	O
+or	O
+methodology	O
+[	O
+51	O
+]	O
+.	O
+
+Similar	O
+findings	O
+were	O
+found	O
+in	O
+a	O
+qualitative	O
+study	O
+among	O
+16	O
+nurses	O
+working	O
+from	O
+diverse	O
+practice	O
+settings	O
+(	O
+acute	O
+,	O
+long	O
+-	O
+term	O
+care	O
+,	O
+rehabilitation	O
+and	O
+community	O
+;	O
+from	O
+both	O
+urban	O
+and	O
+rural	O
+areas	O
+)	O
+in	O
+a	O
+health	O
+region	O
+in	O
+western	O
+Canada	O
+.	O
+
+From	O
+the	O
+semi	O
+-	O
+structured	O
+interviews	O
+,	O
+study	O
+participants	B
+expressed	O
+a	O
+desire	O
+for	O
+improved	O
+consultation	O
+and	O
+communication	O
+with	O
+nurses	O
+regarding	O
+changes	O
+to	O
+the	O
+health	O
+care	O
+system	O
+[	O
+52	O
+]	O
+.	O
+
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+
+Another	O
+area	O
+that	O
+was	O
+ranked	O
+highly	O
+was	O
+marketing	O
+strategies	O
+to	O
+increase	O
+high	O
+school	O
+student	O
+and	O
+public	O
+awareness	O
+of	O
+rehabilitation	O
+careers	O
+.	O
+
+These	O
+specific	O
+strategies	O
+were	O
+also	O
+recommended	O
+by	O
+the	O
+Ontario	O
+Hospital	O
+Association	O
+(	O
+OHA	O
+)	O
+in	O
+order	O
+to	O
+establish	O
+a	O
+competitive	O
+position	O
+for	O
+Ontario	O
+hospitals	O
+in	O
+respect	O
+of	O
+recruitment	O
+and	O
+retention	O
+of	O
+health	O
+care	O
+professionals	O
+[	O
+53	O
+]	O
+.	O
+
+Similar	O
+strategies	O
+have	O
+been	O
+developed	O
+by	O
+the	O
+American	O
+Physical	O
+Therapy	O
+Association	O
+(	O
+APTA	O
+)	O
+in	O
+response	O
+to	O
+the	O
+declining	O
+number	O
+of	O
+students	O
+applying	O
+to	O
+Physical	O
+Therapy	O
+Education	O
+Programs	O
+[	O
+54	O
+]	O
+.	O
+
+To	O
+address	O
+this	O
+trend	O
+,	O
+APTA	O
+developed	O
+a	O
+campaign	O
+to	O
+promote	O
+Physical	O
+Therapy	O
+as	O
+the	O
+profession	O
+of	O
+choice	O
+to	O
+high	O
+school	O
+and	O
+college	O
+students	O
+across	O
+the	O
+United	O
+States	O
+.	O
+
+The	O
+potential	O
+components	O
+of	O
+their	O
+plan	O
+included	O
+:	O
+developing	O
+a	O
+"	O
+Recruiting	O
+Kit	O
+"	O
+for	O
+educators	O
+,	O
+students	O
+and	O
+various	O
+APTA	O
+members	O
+to	O
+be	O
+used	O
+in	O
+the	O
+high	O
+school	O
+and	O
+college	O
+settings	O
+to	O
+introduce	O
+Physical	O
+Therapy	O
+as	O
+a	O
+career	O
+;	O
+establishing	O
+public	O
+relations	O
+initiatives	O
+that	O
+demonstrate	O
+the	O
+role	O
+of	O
+Physical	O
+Therapy	O
+in	O
+the	O
+public	O
+arena	O
+targeting	O
+minority	O
+groups	O
+that	O
+are	O
+underrepresented	O
+in	O
+the	O
+profession	O
+;	O
+and	O
+creating	O
+alliances	O
+with	O
+professional	O
+associations	O
+of	O
+high	O
+school	O
+guidance	O
+counsellors	O
+and	O
+educators	O
+.	O
+
+Based	O
+on	O
+our	O
+finding	O
+,	O
+the	O
+APTA	O
+model	O
+may	O
+have	O
+applicability	O
+in	O
+Ontario	O
+.	O
+
+Workload	O
+and	O
+Skill	O
+Mix	O
+
+Of	O
+the	O
+six	O
+Workload	O
+and	O
+Skill	O
+Mix	O
+strategies	O
+only	O
+two	O
+were	O
+highly	O
+rated	O
+:	O
+implementing	O
+a	O
+caseload	O
+management	O
+database	O
+and	O
+using	O
+support	O
+personnel	O
+.	O
+
+Caseload	O
+management	O
+has	O
+been	O
+identified	O
+in	O
+the	O
+literature	O
+as	O
+an	O
+issue	O
+affecting	O
+all	O
+three	O
+rehabilitation	O
+professions	O
+.	O
+
+For	O
+example	O
+,	O
+in	O
+physiotherapy	O
+,	O
+Christie	O
+'	O
+s	O
+study	O
+[	O
+55	O
+]	O
+found	O
+that	O
+caseload	O
+expectations	O
+tended	O
+to	O
+be	O
+significantly	O
+higher	O
+than	O
+the	O
+reality	O
+and	O
+that	O
+caseload	O
+varies	O
+across	O
+different	O
+programs	O
+.	O
+
+Similarly	O
+,	O
+the	O
+Canadian	O
+Association	O
+of	O
+Speech	O
+-	O
+Language	O
+Pathologists	O
+and	O
+Audiologists	O
+(	O
+CASPLA	O
+)	O
+survey	O
+indicated	O
+that	O
+factors	O
+affecting	O
+the	O
+workload	O
+of	O
+SLPs	O
+include	O
+delivery	O
+models	O
+,	O
+client	O
+disorder	O
+,	O
+severity	O
+and	O
+work	O
+setting	O
+[	O
+56	O
+]	O
+.	O
+
+A	O
+literature	O
+review	O
+and	O
+environmental	O
+scan	O
+undertaken	O
+by	O
+the	O
+Canadian	O
+Association	O
+of	O
+Occupational	O
+Therapists	O
+(	O
+CAOT	O
+)	O
+proposed	O
+that	O
+guiding	O
+principles	O
+for	O
+caseload	O
+management	O
+should	O
+include	O
+:	O
+evidence	O
+-	O
+based	O
+occupational	O
+therapy	O
+,	O
+cost	O
+-	O
+effectiveness	O
+,	O
+accountability	O
+,	O
+professional	O
+leadership	O
+and	O
+expert	O
+judgment	O
+,	O
+comprehensiveness	O
+and	O
+flexibility	O
+[	O
+57	O
+]	O
+.	O
+
+Therefore	O
+,	O
+upon	O
+implementation	O
+of	O
+a	O
+caseload	O
+management	O
+database	O
+for	O
+rehabilitation	O
+,	O
+key	O
+factors	O
+to	O
+consider	O
+include	O
+workplace	O
+setting	O
+and	O
+client	O
+service	O
+delivery	O
+models	O
+.	O
+
+The	O
+other	O
+highly	O
+rated	O
+Workload	O
+and	O
+Skill	O
+Mix	O
+strategy	O
+was	O
+the	O
+use	O
+of	O
+support	O
+personnel	O
+(	O
+i	O
+.	O
+e	O
+.	O
+physiotherapy	O
+assistants	O
+or	O
+exercise	O
+therapists	O
+)	O
+to	O
+increase	O
+efficiency	O
+of	O
+utilization	O
+of	O
+scarcer	O
+and	O
+higher	O
+order	O
+rehabilitation	O
+competencies	O
+.	O
+
+Considerations	O
+for	O
+implementing	O
+this	O
+strategy	O
+include	O
+addressing	O
+key	O
+issues	O
+such	O
+supply	O
+,	O
+standards	O
+of	O
+education	O
+,	O
+standards	O
+of	O
+practice	O
+and	O
+accreditation	O
+.	O
+
+These	O
+are	O
+highlighted	O
+in	O
+an	O
+article	O
+by	O
+Salvatori	O
+[	O
+58	O
+]	O
+who	O
+reported	O
+that	O
+the	O
+actual	O
+number	O
+of	O
+OT	O
+personnel	O
+delivering	O
+OT	O
+services	O
+in	O
+Canada	O
+remains	O
+unknown	O
+and	O
+that	O
+there	O
+are	O
+no	O
+national	O
+standards	O
+of	O
+education	O
+nor	O
+accreditation	O
+process	O
+for	O
+OT	O
+assistants	O
+.	O
+
+CAOT	O
+believes	O
+that	O
+in	O
+order	O
+to	O
+utilize	O
+support	O
+personnel	O
+appropriately	O
+,	O
+studies	O
+on	O
+human	B
+resource	O
+needs	O
+for	O
+occupational	O
+therapy	O
+and	O
+support	O
+personnel	O
+are	O
+first	O
+needed	O
+with	O
+input	O
+from	O
+OTs	O
+,	O
+stakeholders	O
+,	O
+funders	O
+,	O
+decision	O
+makers	O
+and	O
+health	O
+policy	O
+planners	O
+[	O
+59	O
+]	O
+.	O
+
+Since	O
+there	O
+is	O
+a	O
+lack	O
+of	O
+competency	O
+profiles	O
+related	O
+to	O
+the	O
+role	O
+,	O
+responsibilities	O
+,	O
+and	O
+supervision	O
+of	O
+assistants	O
+,	O
+particularly	O
+with	O
+regards	O
+to	O
+delivering	O
+services	O
+in	O
+unsupervised	O
+community	O
+-	O
+based	O
+settings	O
+,	O
+the	O
+type	O
+of	O
+workplace	O
+setting	O
+where	O
+this	O
+strategy	O
+may	O
+be	O
+implemented	O
+should	O
+be	O
+considered	O
+[	O
+58	O
+]	O
+.	O
+
+Education	O
+and	O
+Training	O
+
+Given	O
+that	O
+60	O
+%	O
+of	O
+highly	O
+rated	O
+Education	O
+and	O
+Training	O
+strategies	O
+targeted	O
+rural	O
+and	O
+remote	O
+practices	O
+underscores	O
+the	O
+importance	O
+of	O
+specific	O
+strategies	O
+for	O
+rural	O
+and	O
+remote	O
+areas	O
+in	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
+.	O
+
+The	O
+need	O
+to	O
+build	O
+on	O
+existing	O
+mechanisms	O
+to	O
+expand	O
+the	O
+availability	O
+of	O
+rural	O
+and	O
+remote	O
+clinical	O
+placements	O
+by	O
+providing	O
+financial	O
+and	O
+accommodation	O
+support	O
+was	O
+ranked	O
+among	O
+the	O
+top	O
+two	O
+most	O
+important	O
+and	O
+feasible	O
+education	O
+strategies	O
+for	O
+rehabilitation	O
+professionals	O
+.	O
+
+Not	O
+only	O
+has	O
+this	O
+strategy	O
+been	O
+used	O
+as	O
+a	O
+recruitment	O
+tool	O
+for	O
+rehabilitation	O
+students	O
+,	O
+it	O
+has	O
+also	O
+been	O
+reported	O
+by	O
+Solomon	O
+et	O
+al	O
+.	O
+
+[	O
+34	O
+]	O
+to	O
+be	O
+effective	O
+in	O
+retaining	O
+OTs	O
+and	O
+PTs	O
+in	O
+underserviced	O
+Northwestern	O
+Ontario	O
+communities	O
+.	O
+
+Respondents	O
+from	O
+Solomon	O
+et	O
+al	O
+.	O
+'	O
+s	O
+study	O
+reported	O
+that	O
+the	O
+top	O
+three	O
+benefits	O
+of	O
+supervising	O
+students	O
+were	O
+that	O
+it	O
+stimulates	O
+thinking	O
+,	O
+it	O
+provides	O
+opportunity	O
+to	O
+contribute	O
+to	O
+the	O
+profession	O
+and	O
+that	O
+it	O
+provides	O
+access	O
+to	O
+current	O
+information	O
+.	O
+
+The	O
+reported	O
+disadvantages	O
+however	O
+was	O
+that	O
+it	O
+was	O
+time	O
+-	O
+consuming	O
+and	O
+students	O
+contributed	O
+stress	O
+to	O
+the	O
+working	O
+environment	O
+.	O
+
+Similarly	O
+,	O
+a	O
+two	O
+-	O
+part	O
+study	O
+found	O
+substantial	O
+gaps	O
+between	O
+financial	O
+incentives	O
+students	O
+deem	O
+important	O
+in	O
+the	O
+creation	O
+of	O
+an	O
+appealing	O
+clinical	O
+placement	O
+opportunity	O
+and	O
+the	O
+actual	O
+provisions	O
+offered	O
+to	O
+them	O
+by	O
+Southeastern	O
+Ontario	O
+communities	O
+[	O
+60	O
+,	O
+61	O
+]	O
+.	O
+
+Although	O
+OT	O
+and	O
+PT	O
+students	O
+reported	O
+that	O
+they	O
+were	O
+more	O
+willing	O
+to	O
+complete	O
+a	O
+clinical	O
+placement	O
+in	O
+an	O
+underserviced	O
+community	O
+if	O
+provided	O
+travel	O
+stipends	O
+,	O
+rent	O
+-	O
+free	O
+housing	O
+and	O
+interprofessional	O
+education	O
+opportunities	O
+,	O
+the	O
+majority	O
+of	O
+these	O
+incentives	O
+were	O
+only	O
+available	O
+to	O
+medical	O
+students	O
+.	O
+
+In	O
+addition	O
+to	O
+training	O
+students	O
+for	O
+rural	O
+and	O
+remote	O
+practice	O
+,	O
+a	O
+longitudinal	O
+study	O
+reported	O
+that	O
+perceived	O
+opportunity	O
+for	O
+career	O
+development	O
+was	O
+the	O
+most	O
+significant	O
+factor	O
+related	O
+to	O
+job	O
+turnover	O
+and	O
+regional	O
+attrition	O
+among	O
+physiotherapists	O
+working	O
+in	O
+Northern	O
+Ontario	O
+[	O
+5	O
+]	O
+.	O
+
+Therefore	O
+developing	O
+workforce	O
+strategies	O
+for	O
+rehabilitation	O
+therapists	O
+working	O
+in	O
+these	O
+areas	O
+should	O
+be	O
+among	O
+one	O
+of	O
+the	O
+priority	O
+areas	O
+in	O
+HHR	O
+planning	O
+.	O
+
+Professional	O
+Development	O
+
+Our	O
+findings	O
+indicate	O
+that	O
+the	O
+theme	O
+with	O
+the	O
+largest	O
+number	O
+of	O
+strategies	O
+that	O
+were	O
+considered	O
+important	O
+and	O
+feasible	O
+to	O
+implement	O
+as	O
+part	O
+of	O
+HHR	O
+planning	O
+was	O
+professional	O
+development	O
+.	O
+
+Many	O
+were	O
+specific	O
+to	O
+rural	O
+and	O
+remote	O
+areas	O
+.	O
+
+Although	O
+the	O
+importance	O
+of	O
+continuous	O
+professional	O
+development	O
+(	O
+CPD	O
+)	O
+in	O
+recruitment	O
+and	O
+retention	O
+is	O
+well	O
+recognized	O
+,	O
+a	O
+Canadian	O
+study	O
+reported	O
+several	O
+barriers	O
+to	O
+its	O
+implementation	O
+[	O
+62	O
+]	O
+.	O
+
+In	O
+the	O
+case	O
+of	O
+OTs	O
+employed	O
+in	O
+public	O
+settings	O
+in	O
+Nova	O
+Scotia	O
+,	O
+Townsend	O
+et	O
+al	O
+.	O
+
+(	O
+2006	O
+)	O
+found	O
+that	O
+the	O
+most	O
+powerful	O
+deterrent	O
+for	O
+CPD	O
+was	O
+the	O
+lack	O
+of	O
+support	O
+from	O
+workplace	O
+policies	O
+.	O
+
+Based	O
+on	O
+their	O
+study	O
+results	O
+,	O
+the	O
+use	O
+of	O
+CPD	O
+as	O
+a	O
+recruitment	O
+and	O
+retention	O
+strategy	O
+was	O
+highly	O
+influenced	O
+by	O
+gender	O
+issues	O
+,	O
+work	O
+-	O
+life	O
+balance	O
+,	O
+career	O
+advancement	O
+,	O
+working	O
+conditions	O
+,	O
+geographical	O
+location	O
+,	O
+professional	O
+versus	O
+employer	O
+responsibility	O
+,	O
+and	O
+employee	O
+benefits	O
+.	O
+
+Although	O
+occupational	O
+therapy	O
+is	O
+a	O
+female	O
+-	O
+dominated	O
+profession	O
+,	O
+workplace	O
+policies	O
+did	O
+not	O
+address	O
+issues	O
+of	O
+gender	O
+.	O
+
+For	O
+example	O
+,	O
+therapists	O
+in	O
+this	O
+study	O
+indicated	O
+that	O
+CPD	O
+competes	O
+with	O
+family	O
+commitments	O
+,	O
+therefore	O
+these	O
+activities	O
+are	O
+"	O
+done	O
+largely	O
+during	O
+personal	O
+time	O
+,	O
+mainly	O
+at	O
+their	O
+own	O
+cost	O
+,	O
+and	O
+on	O
+top	O
+of	O
+childcare	O
+,	O
+eldercare	O
+,	O
+homemaking	O
+and	O
+other	O
+family	O
+responsibilities	O
+"	O
+[	O
+62	O
+]	O
+.	O
+
+In	O
+addition	O
+,	O
+heavy	O
+workloads	O
+,	O
+lack	O
+of	O
+salary	O
+and	O
+career	O
+incentives	O
+,	O
+and	O
+lack	O
+of	O
+policy	O
+and	O
+funding	O
+support	O
+are	O
+all	O
+barriers	O
+to	O
+CPD	O
+.	O
+
+These	O
+issues	O
+become	O
+more	O
+pronounced	O
+in	O
+rural	O
+and	O
+remote	O
+settings	O
+because	O
+smaller	O
+communities	O
+often	O
+only	O
+have	O
+one	O
+therapist	O
+;	O
+hence	O
+the	O
+systemic	O
+pressure	O
+of	O
+workload	O
+demands	O
+makes	O
+it	O
+difficult	O
+for	O
+the	O
+therapist	O
+to	O
+leave	O
+patient	B
+care	O
+.	O
+
+OTs	O
+from	O
+this	O
+study	O
+also	O
+questioned	O
+who	O
+was	O
+responsible	O
+for	O
+CPD	O
+.	O
+
+Some	O
+felt	O
+that	O
+it	O
+was	O
+the	O
+professional	O
+'	O
+s	O
+responsibility	O
+while	O
+others	O
+felt	O
+that	O
+it	O
+was	O
+the	O
+responsibility	O
+of	O
+the	O
+employer	O
+to	O
+provide	O
+CPD	O
+opportunities	O
+.	O
+
+The	O
+primary	O
+limitation	O
+employers	O
+faced	O
+was	O
+the	O
+lack	O
+of	O
+financial	O
+resources	O
+,	O
+however	O
+giving	O
+employees	O
+time	O
+off	O
+without	O
+pay	O
+was	O
+an	O
+alternative	O
+strategy	O
+utilized	O
+instead	O
+of	O
+funding	O
+professional	O
+development	O
+activities	O
+.	O
+
+Although	O
+there	O
+are	O
+professional	O
+and	O
+provincial	O
+variations	O
+in	O
+funding	O
+for	O
+CPD	O
+across	O
+Canada	O
+,	O
+these	O
+results	O
+are	O
+informative	O
+in	O
+that	O
+it	O
+highlights	O
+the	O
+need	O
+for	O
+employers	O
+to	O
+consider	O
+how	O
+workplace	O
+policies	O
+can	O
+affect	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+.	O
+
+Limitations	O
+of	O
+this	O
+study	O
+should	O
+be	O
+noted	O
+.	O
+
+First	O
+,	O
+the	O
+majority	O
+of	O
+the	O
+strategies	O
+were	O
+obtained	O
+from	O
+the	O
+grey	O
+literature	O
+that	O
+is	O
+not	O
+subject	O
+to	O
+the	O
+same	O
+scrutiny	O
+as	O
+the	O
+peer	O
+-	O
+reviewed	O
+literature	O
+.	O
+
+Second	O
+,	O
+almost	O
+none	O
+of	O
+the	O
+strategies	O
+were	O
+specifically	O
+developed	O
+for	O
+rehabilitation	O
+professionals	O
+and	O
+in	O
+many	O
+cases	O
+had	O
+to	O
+be	O
+re	O
+-	O
+worded	O
+to	O
+fit	O
+the	O
+rehabilitation	O
+context	O
+.	O
+
+There	O
+is	O
+a	O
+lack	O
+of	O
+research	O
+on	O
+rehabilitation	O
+clinicians	O
+'	O
+perspectives	O
+on	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+;	O
+therefore	O
+future	O
+research	O
+should	O
+focus	O
+on	O
+investigating	O
+this	O
+area	O
+.	O
+
+Third	O
+,	O
+during	O
+the	O
+face	O
+-	O
+to	O
+-	O
+face	O
+meeting	O
+,	O
+bias	O
+could	O
+have	O
+resulted	O
+from	O
+panelists	O
+whose	O
+opinion	O
+may	O
+have	O
+influenced	O
+others	O
+significantly	O
+,	O
+especially	O
+if	O
+members	O
+came	O
+from	O
+similar	O
+workplace	O
+settings	O
+.	O
+
+The	O
+facilitator	O
+of	O
+the	O
+expert	O
+panels	O
+however	O
+,	O
+followed	O
+a	O
+strict	O
+process	O
+for	O
+managing	O
+the	O
+discussion	O
+and	O
+ensured	O
+that	O
+all	O
+panelists	O
+were	O
+given	O
+the	O
+opportunity	O
+to	O
+express	O
+their	O
+opinions	O
+.	O
+
+Finally	O
+,	O
+although	O
+some	O
+strategies	O
+such	O
+as	O
+competitive	O
+wage	O
+packages	O
+,	O
+training	O
+/	O
+growth	O
+opportunities	O
+and	O
+professional	O
+development	O
+are	O
+viewed	O
+as	O
+both	O
+a	O
+recruitment	O
+and	O
+retention	O
+incentive	O
+,	O
+other	O
+strategies	O
+do	O
+not	O
+overlap	O
+and	O
+are	O
+appropriate	O
+for	O
+only	O
+one	O
+of	O
+the	O
+two	O
+tasks	O
+.	O
+
+For	O
+example	O
+,	O
+increasing	O
+public	O
+awareness	O
+of	O
+rehabilitation	O
+careers	O
+,	O
+providing	O
+rural	O
+and	O
+remote	O
+orientation	O
+packages	O
+and	O
+family	O
+relocation	O
+programs	O
+are	O
+only	O
+appropriate	O
+for	O
+attracting	O
+a	O
+worker	O
+while	O
+ensuring	O
+open	O
+and	O
+timely	O
+communication	O
+may	O
+be	O
+seen	O
+as	O
+a	O
+strategy	O
+only	O
+for	O
+retention	O
+.	O
+
+Future	O
+research	O
+should	O
+therefore	O
+consider	O
+studying	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+separately	O
+so	O
+that	O
+a	O
+distinction	O
+between	O
+the	O
+two	O
+can	O
+be	O
+made	O
+.	O
+
+Conclusion	O
+
+This	O
+study	O
+identified	O
+34	O
+strategies	O
+that	O
+should	O
+be	O
+considered	O
+as	O
+important	O
+and	O
+feasible	O
+for	O
+implementation	O
+as	O
+part	O
+of	O
+HHR	O
+planning	O
+for	O
+rehabilitation	O
+professionals	O
+.	O
+
+Although	O
+the	O
+highest	O
+ranked	O
+strategies	O
+focused	O
+on	O
+areas	O
+of	O
+Quality	O
+of	O
+Worklife	O
+and	O
+Work	O
+Environment	O
+,	O
+Financial	O
+Incentives	O
+and	O
+Marketing	O
+and	O
+Professional	O
+Development	O
+,	O
+key	O
+factors	O
+that	O
+need	O
+to	O
+be	O
+considered	O
+in	O
+the	O
+context	O
+of	O
+implementation	O
+include	O
+:	O
+workplace	O
+setting	O
+,	O
+geographical	O
+location	O
+and	O
+gender	O
+issues	O
+.	O
+
+While	O
+this	O
+is	O
+the	O
+first	O
+study	O
+to	O
+our	O
+knowledge	O
+that	O
+provides	O
+a	O
+comprehensive	O
+list	O
+of	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+relevant	O
+to	O
+rehabilitation	O
+professionals	O
+,	O
+more	O
+information	O
+is	O
+needed	O
+for	O
+the	O
+development	O
+of	O
+a	O
+HHR	O
+plan	O
+.	O
+
+Information	O
+on	O
+trends	O
+in	O
+labour	O
+force	O
+participation	O
+as	O
+well	O
+as	O
+knowledge	O
+regarding	O
+the	O
+use	O
+and	O
+effectiveness	O
+of	O
+recruitment	O
+and	O
+retention	O
+strategies	O
+for	O
+rehabilitation	O
+professionals	O
+is	O
+needed	O
+.	O
+
+More	O
+importantly	O
+,	O
+the	O
+success	O
+of	O
+implementing	O
+and	O
+sustaining	O
+such	O
+strategies	O
+requires	O
+future	O
+research	O
+to	O
+validate	O
+these	O
+strategies	O
+from	O
+the	O
+perspective	O
+of	O
+rehabilitation	O
+clinicians	O
+and	O
+human	B
+resource	O
+decisions	O
+makers	O
+(	O
+i	O
+.	O
+e	O
+.	O
+local	O
+government	O
+,	O
+stakeholders	O
+,	O
+etc	O
+.	O
+)	O
+so	O
+that	O
+specific	O
+barriers	O
+and	O
+challenges	O
+can	O
+be	O
+identified	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+authors	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+DT	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+,	O
+conducted	O
+the	O
+literature	O
+review	O
+,	O
+analyzed	O
+and	O
+interpreted	O
+the	O
+results	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+LMH	O
+,	O
+AD	O
+,	O
+DB	O
+and	O
+KB	O
+were	O
+involved	O
+in	O
+providing	O
+feedback	O
+and	O
+editing	O
+the	O
+content	O
+of	O
+the	O
+manuscript	O
+.	O
+
+MDL	O
+recommended	O
+participants	B
+for	O
+the	O
+expert	O
+panel	O
+and	O
+was	O
+involved	O
+in	O
+providing	O
+feedback	O
+and	O
+editing	O
+the	O
+content	O
+of	O
+the	O
+manuscript	O
+.	O
+
+SJ	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+,	O
+recommended	O
+participants	B
+for	O
+the	O
+expert	O
+panel	O
+,	O
+organized	O
+and	O
+consolidated	O
+strategies	O
+,	O
+interpreted	O
+the	O
+data	O
+and	O
+edited	O
+the	O
+content	O
+of	O
+the	O
+manuscript	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+A	O
+life	O
+threatening	O
+uterine	O
+inversion	O
+and	O
+massive	O
+post	O
+partum	O
+hemorrhage	O
+caused	O
+by	O
+placenta	O
+accrete	O
+during	O
+Caesarean	O
+section	O
+in	O
+a	O
+primigravida	O
+:	O
+a	O
+case	O
+report	O
+
+Abstract	O
+
+Background	O
+
+A	O
+32	O
+-	O
+year	O
+-	O
+old	O
+Caucasian	O
+primigravida	O
+was	O
+admitted	O
+for	O
+elective	O
+Caesarean	O
+Section	O
+at	O
+36	O
+weeks	O
+and	O
+6	O
+days	O
+with	O
+the	O
+diagnosis	O
+of	O
+preeclampsia	O
+.	O
+
+Case	O
+presentation	O
+
+Traction	O
+of	O
+the	O
+umbilical	O
+cord	O
+after	O
+delivery	O
+of	O
+a	O
+healthy	O
+baby	O
+resulted	O
+in	O
+uterine	O
+inversion	O
+.	O
+
+The	O
+placenta	O
+was	O
+found	O
+to	O
+be	O
+densely	O
+adherent	O
+to	O
+the	O
+posterior	O
+uterine	O
+wall	O
+.	O
+
+Piecemeal	O
+excision	O
+of	O
+the	O
+placenta	O
+as	O
+close	O
+as	O
+possible	O
+to	O
+the	O
+uterine	O
+lining	O
+was	O
+then	O
+performed	O
+.	O
+
+Conclusion	O
+
+In	O
+this	O
+way	O
+we	O
+were	O
+able	O
+to	O
+control	O
+a	O
+massive	O
+post	O
+partum	O
+hemorrhage	O
+and	O
+preserve	O
+the	O
+fertility	O
+of	O
+the	O
+patient	B
+.	O
+
+Background	O
+
+Placenta	O
+accreta	O
+is	O
+defined	O
+as	O
+abnormal	O
+adherence	O
+,	O
+either	O
+in	O
+whole	O
+or	O
+in	O
+part	O
+of	O
+the	O
+afterbirth	O
+to	O
+the	O
+underlying	O
+uterine	O
+wall	O
+.	O
+
+Placenta	O
+accreta	O
+and	O
+other	O
+pathological	O
+placentations	O
+(	O
+such	O
+as	O
+increta	O
+,	O
+percreta	O
+)	O
+are	O
+rare	O
+complications	O
+of	O
+pregnancy	O
+with	O
+potential	O
+life	O
+threatening	O
+and	O
+fertility	O
+threatening	O
+consequences	O
+.	O
+
+The	O
+incidence	O
+of	O
+placenta	O
+accreta	O
+has	O
+increased	O
+ten	O
+times	O
+over	O
+the	O
+last	O
+fifteen	O
+years	O
+,	O
+which	O
+reflects	O
+the	O
+increase	O
+in	O
+the	O
+rate	O
+of	O
+Caesarean	O
+Sections	O
+(	O
+CS	O
+)	O
+[	O
+1	O
+]	O
+.	O
+
+Placenta	O
+accreta	O
+has	O
+become	O
+the	O
+most	O
+important	O
+cause	O
+of	O
+peripartum	O
+hysterectomy	O
+.	O
+
+A	O
+life	O
+threatening	O
+acute	O
+uterine	O
+inversion	O
+and	O
+massive	O
+PPH	O
+can	O
+be	O
+caused	O
+by	O
+placenta	O
+accreta	O
+during	O
+CS	O
+but	O
+seldom	O
+in	O
+a	O
+primigravida	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+Case	O
+presentation	O
+
+A	O
+32	O
+year	O
+old	O
+,	O
+primigravida	O
+,	O
+was	O
+admitted	O
+in	O
+a	O
+District	O
+General	O
+Hospital	O
+for	O
+elective	O
+Caesarean	O
+section	O
+at	O
+36	O
+weeks	O
+and	O
+6	O
+days	O
+with	O
+the	O
+diagnosis	O
+of	O
+preeclampsia	O
+.	O
+
+She	O
+had	O
+two	O
+antenatal	O
+ultrasound	O
+examinations	O
+showing	O
+a	O
+healthy	O
+fetus	O
+and	O
+posterior	O
+fundal	O
+placenta	O
+.	O
+
+The	O
+patient	B
+had	O
+lower	O
+segment	O
+CS	O
+of	O
+a	O
+healthy	O
+male	O
+infant	B
+under	O
+spinal	O
+anesthesia	O
+.	O
+
+The	O
+placenta	O
+was	O
+found	O
+to	O
+be	O
+densely	O
+adherent	O
+to	O
+the	O
+posterior	O
+uterine	O
+wall	O
+.	O
+
+Traction	O
+of	O
+the	O
+umbilical	O
+cord	O
+was	O
+applied	O
+and	O
+subsequently	O
+resulted	O
+in	O
+uterine	O
+inversion	O
+.	O
+
+The	O
+placenta	O
+was	O
+removed	O
+by	O
+'	O
+piecemeal	O
+'	O
+excising	O
+as	O
+close	O
+as	O
+possible	O
+to	O
+the	O
+uterine	O
+lining	O
+.	O
+
+About	O
+80	O
+%	O
+of	O
+the	O
+placental	O
+tissue	O
+was	O
+removed	O
+until	O
+the	O
+uterine	O
+inversion	O
+was	O
+corrected	O
+.	O
+
+The	O
+uterus	O
+was	O
+closed	O
+in	O
+two	O
+layers	O
+.	O
+
+Two	O
+intra	O
+-	O
+abdominal	O
+drains	O
+were	O
+sited	O
+.	O
+
+The	O
+estimated	O
+blood	O
+loss	O
+was	O
+2	O
+.	O
+5	O
+litres	O
+and	O
+five	O
+units	O
+of	O
+blood	O
+were	O
+transfused	O
+together	O
+with	O
+2	O
+units	O
+of	O
+FFP	O
+during	O
+intra	O
+-	O
+operative	O
+and	O
+post	O
+-	O
+operative	O
+period	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+patient	B
+was	O
+treated	O
+with	O
+intravenous	O
+oxytocin	O
+infusion	O
+,	O
+pr	O
+misoprostol	O
+and	O
+antibiotics	O
+.	O
+
+On	O
+the	O
+second	O
+post	O
+partum	O
+day	O
+,	O
+vaginal	O
+Doppler	O
+ultrasound	O
+scan	O
+showed	O
+significant	O
+amount	O
+of	O
+placental	O
+tissues	O
+with	O
+increased	O
+vascularity	O
+measuring	O
+2	O
+.	O
+7	O
+x	O
+6	O
+.	O
+6	O
+x	O
+6	O
+.	O
+8	O
+cms	O
+within	O
+the	O
+endometrial	O
+cavity	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+The	O
+patient	B
+was	O
+discharged	O
+on	O
+the	O
+fifth	O
+post	O
+-	O
+operative	O
+day	O
+with	O
+a	O
+conservative	O
+management	O
+.	O
+
+A	O
+follow	O
+up	O
+Ultrasound	O
+scan	O
+after	O
+two	O
+weeks	O
+showed	O
+reduction	O
+of	O
+placental	O
+mass	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+there	O
+was	O
+significant	O
+decrease	O
+in	O
+serum	O
+beta	O
+HCG	O
+levels	O
+from	O
+2300	O
+u	O
+/	O
+L	O
+on	O
+day	O
+1	O
+to	O
+13	O
+u	O
+/	O
+L	O
+at	O
+four	O
+weeks	O
+post	O
+operatively	O
+.	O
+
+The	O
+patient	B
+remained	O
+with	O
+minimal	O
+vaginal	O
+bleeding	O
+without	O
+abdominal	O
+pain	O
+.	O
+
+She	O
+had	O
+two	O
+normal	O
+periods	O
+after	O
+stopping	O
+breastfeeding	O
+and	O
+was	O
+feeling	O
+well	O
+.	O
+
+She	O
+was	O
+discharged	O
+from	O
+the	O
+early	O
+pregnancy	O
+unit	O
+.	O
+
+Discussion	O
+
+A	O
+life	O
+-	O
+threatening	O
+uterine	O
+inversion	O
+can	O
+be	O
+rarely	O
+caused	O
+by	O
+placenta	O
+accreta	O
+[	O
+2	O
+]	O
+.	O
+
+Placenta	O
+accreta	O
+classically	O
+presents	O
+with	O
+retained	O
+placenta	O
+and	O
+hemorrhage	O
+.	O
+
+The	O
+association	O
+between	O
+uterine	O
+inversion	O
+and	O
+placenta	O
+accreta	O
+is	O
+unclear	O
+,	O
+however	O
+,	O
+strong	O
+traction	O
+on	O
+the	O
+umbilical	O
+cord	O
+with	O
+fundal	O
+placenta	O
+,	O
+excessive	O
+fundal	O
+pressure	O
+,	O
+relaxed	O
+uterus	O
+,	O
+short	O
+umbilical	O
+cord	O
+,	O
+uterine	O
+anomalies	O
+and	O
+antepartum	O
+use	O
+of	O
+magnesium	O
+sulphate	O
+are	O
+known	O
+associated	O
+factors	O
+[	O
+2	O
+]	O
+.	O
+
+Uterine	O
+inversion	O
+and	O
+retain	O
+placenta	O
+accreta	O
+can	O
+both	O
+be	O
+fatal	O
+complications	O
+[	O
+3	O
+]	O
+.	O
+
+In	O
+the	O
+case	O
+described	O
+the	O
+placenta	O
+accreta	O
+was	O
+complicated	O
+by	O
+uterine	O
+inversion	O
+and	O
+subsequent	O
+massive	O
+post	O
+partum	O
+hemorrhage	O
+,	O
+significantly	O
+increasing	O
+the	O
+risk	O
+of	O
+maternal	O
+mortality	O
+.	O
+
+Massive	O
+post	O
+partum	O
+hemorrhage	O
+is	O
+a	O
+major	O
+cause	O
+of	O
+maternal	O
+mortality	O
+in	O
+the	O
+United	O
+Kingdom	O
+(	O
+why	O
+women	B
+die	O
+latest	O
+report	O
+)	O
+[	O
+4	O
+]	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+the	O
+placenta	O
+was	O
+clamped	O
+as	O
+close	O
+to	O
+the	O
+uterine	O
+cavity	O
+as	O
+possible	O
+and	O
+cut	O
+.	O
+
+The	O
+base	O
+of	O
+the	O
+placenta	O
+was	O
+overrun	O
+with	O
+haemostatic	O
+sutures	O
+and	O
+this	O
+was	O
+repeated	O
+until	O
+as	O
+much	O
+of	O
+the	O
+placenta	O
+as	O
+possible	O
+was	O
+removed	O
+(	O
+Figure	O
+4	O
+)	O
+.	O
+
+Placental	O
+removal	O
+enabled	O
+correction	O
+of	O
+uterine	O
+inversion	O
+.	O
+
+Despite	O
+the	O
+many	O
+conditions	O
+associated	O
+with	O
+uterine	O
+inversion	O
+risk	O
+assessment	O
+is	O
+often	O
+lacking	O
+making	O
+the	O
+condition	O
+usually	O
+unexpected	O
+at	O
+the	O
+time	O
+of	O
+presentation	O
+.	O
+
+The	O
+association	O
+between	O
+abnormal	O
+placentation	O
+such	O
+as	O
+placenta	O
+accreta	O
+and	O
+uterine	O
+inversion	O
+is	O
+well	O
+supported	O
+[	O
+2	O
+]	O
+.	O
+
+Therefore	O
+,	O
+we	O
+advocate	O
+antenatal	O
+evaluation	O
+and	O
+risk	O
+assessment	O
+for	O
+placenta	O
+accreta	O
+[	O
+5	O
+]	O
+.	O
+
+Prenatal	O
+Ultrasound	O
+reported	O
+sensitivity	O
+of	O
+94	O
+%	O
+and	O
+specificity	O
+of	O
+79	O
+%	O
+for	O
+placenta	O
+accreta	O
+,	O
+but	O
+offer	O
+no	O
+more	O
+than	O
+provisional	O
+diagnostic	O
+probability	O
+statement	O
+[	O
+6	O
+]	O
+.	O
+
+Moreover	O
+,	O
+because	O
+45	O
+%	O
+of	O
+placenta	O
+accreta	O
+cases	O
+were	O
+not	O
+detected	O
+by	O
+ultrasound	O
+,	O
+it	O
+is	O
+important	O
+to	O
+consider	O
+avoiding	O
+manual	O
+removal	O
+of	O
+placenta	O
+if	O
+there	O
+were	O
+intraoperative	O
+signs	O
+of	O
+accreta	O
+[	O
+6	O
+]	O
+.	O
+
+If	O
+clinically	O
+or	O
+sonographically	O
+the	O
+patient	B
+is	O
+suspected	O
+antenatally	O
+to	O
+be	O
+at	O
+risk	O
+of	O
+placenta	O
+accreta	O
+,	O
+appropriate	O
+management	O
+options	O
+should	O
+be	O
+considered	O
+,	O
+such	O
+as	O
+attempted	O
+conservative	O
+management	O
+or	O
+hysterectomy	O
+and	O
+counseling	O
+provided	O
+about	O
+potential	O
+sequelae	O
+[	O
+6	O
+]	O
+.	O
+
+The	O
+traditional	O
+management	O
+is	O
+abdominal	O
+hysterectomy	O
+,	O
+but	O
+this	O
+operation	O
+terminates	O
+fertility	O
+and	O
+may	O
+have	O
+devastating	O
+psychological	O
+effects	O
+.	O
+
+However	O
+,	O
+in	O
+correct	O
+circumstances	O
+,	O
+a	O
+conservative	O
+approach	O
+may	O
+be	O
+suitable	O
+.	O
+
+Conservative	O
+management	O
+of	O
+abnormally	O
+invasive	O
+placentation	O
+can	O
+be	O
+effective	O
+and	O
+fertility	O
+can	O
+be	O
+preserved	O
+.	O
+
+It	O
+should	O
+be	O
+only	O
+considered	O
+in	O
+highly	O
+selected	O
+cases	O
+when	O
+blood	O
+loss	O
+is	O
+minimal	O
+and	O
+there	O
+is	O
+wish	O
+for	O
+fertility	O
+preservation	O
+[	O
+7	O
+]	O
+.	O
+
+For	O
+women	B
+who	O
+want	O
+to	O
+preserve	O
+their	O
+fertility	O
+the	O
+placenta	O
+should	O
+be	O
+left	O
+intact	O
+if	O
+possible	O
+after	O
+caesarean	O
+delivery	O
+as	O
+this	O
+approach	O
+lowers	O
+the	O
+risk	O
+of	O
+subsequent	O
+hysterectomy	O
+from	O
+85	O
+%	O
+to	O
+15	O
+%	O
+.	O
+
+For	O
+women	B
+who	O
+have	O
+completed	O
+their	O
+family	O
+,	O
+hysterectomy	O
+with	O
+placenta	O
+left	O
+in	O
+situ	O
+is	O
+preferable	O
+to	O
+lower	O
+the	O
+maternal	O
+morbidity	O
+rates	O
+[	O
+6	O
+]	O
+.	O
+
+This	O
+case	O
+report	O
+involved	O
+conservative	O
+management	O
+.	O
+
+Peripartum	O
+hysterectomy	O
+was	O
+avoided	O
+and	O
+the	O
+aim	O
+was	O
+to	O
+preserve	O
+fertility	O
+.	O
+
+Prophylactic	O
+antibiotics	O
+,	O
+post	O
+partum	O
+oxytocics	O
+and	O
+the	O
+use	O
+of	O
+misoprostol	O
+post	O
+operatively	O
+helped	O
+to	O
+prevent	O
+further	O
+post	O
+partum	O
+hemorrhage	O
+.	O
+
+When	O
+a	O
+patient	B
+isinitially	O
+opted	O
+for	O
+conservative	O
+management	O
+,	O
+the	O
+possibility	O
+of	O
+recurrence	O
+should	O
+be	O
+discussed	O
+[	O
+8	O
+]	O
+.	O
+
+Furthermore	O
+,	O
+placentation	O
+should	O
+be	O
+carefully	O
+monitored	O
+for	O
+recurrence	O
+in	O
+any	O
+subsequent	O
+pregnancy	O
+,	O
+particularly	O
+if	O
+the	O
+placenta	O
+is	O
+located	O
+at	O
+the	O
+same	O
+site	O
+as	O
+the	O
+previous	O
+placenta	O
+accreta	O
+.	O
+
+Conservative	O
+treatment	O
+for	O
+placenta	O
+accreta	O
+may	O
+be	O
+an	O
+alternative	O
+procedure	O
+in	O
+some	O
+selected	O
+cases	O
+.	O
+
+Conclusion	O
+
+We	O
+suggest	O
+an	O
+alternative	O
+approach	O
+for	O
+managing	O
+uterine	O
+inversion	O
+caused	O
+by	O
+placenta	O
+accreta	O
+that	O
+involved	O
+conservative	O
+management	O
+.	O
+
+This	O
+way	O
+hysterectomy	O
+was	O
+avoided	O
+and	O
+fertility	O
+was	O
+preserved	O
+.	O
+
+Abbreviations	O
+
+CS	O
+:	O
+Caesarean	O
+Section	O
+;	O
+FFP	O
+:	O
+Fresh	O
+Frozen	O
+Plasma	O
+
+Consent	O
+
+Written	O
+informed	O
+consent	O
+was	O
+obtained	O
+from	O
+the	O
+patient	B
+for	O
+publication	O
+of	O
+this	O
+case	O
+report	O
+and	O
+accompanying	O
+images	O
+.	O
+
+A	O
+copy	O
+of	O
+the	O
+written	O
+consent	O
+is	O
+available	O
+for	O
+review	O
+by	O
+the	O
+Editor	O
+-	O
+in	O
+Chief	O
+of	O
+this	O
+journal	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+authors	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+All	O
+authors	O
+have	O
+made	O
+substantial	O
+contribution	O
+to	O
+concept	O
+this	O
+case	O
+report	O
+.	O
+
+Neurogenin2	O
+Directs	O
+Granule	O
+Neuroblast	O
+Production	O
+and	O
+Amplification	O
+while	O
+NeuroD1	O
+Specifies	O
+Neuronal	O
+Fate	O
+during	O
+Hippocampal	O
+Neurogenesis	O
+
+Abstract	O
+
+The	O
+specification	O
+and	O
+differentiation	O
+of	O
+dentate	O
+gyrus	O
+granule	O
+neurons	O
+in	O
+the	O
+hippocampus	O
+require	O
+temporally	O
+and	O
+spatially	O
+coordinated	O
+actions	O
+of	O
+both	O
+intrinsic	O
+and	O
+extrinsic	O
+molecules	O
+.	O
+
+The	O
+basic	O
+helix	O
+-	O
+loop	O
+-	O
+helix	O
+transcription	O
+factor	O
+Neurogenin2	O
+(	O
+Ngn2	O
+)	O
+and	O
+NeuroD1	O
+are	O
+key	O
+regulators	O
+in	O
+these	O
+processes	O
+.	O
+
+Based	O
+on	O
+existing	O
+classification	O
+,	O
+we	O
+analyzed	O
+the	O
+molecular	O
+events	O
+occurring	O
+during	O
+hippocampal	O
+neurogenesis	O
+,	O
+primarily	O
+focusing	O
+on	O
+juvenile	O
+animals	O
+.	O
+
+We	O
+found	O
+that	O
+Ngn2	O
+is	O
+transiently	O
+expressed	O
+by	O
+late	O
+type	O
+-	O
+2a	O
+amplifying	O
+progenitors	O
+.	O
+
+The	O
+Ngn2	O
+progenies	O
+mature	O
+into	O
+hippocampal	O
+granule	O
+neurons	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+loss	O
+of	O
+Ngn2	O
+at	O
+early	O
+stages	O
+of	O
+development	O
+leads	O
+to	O
+a	O
+robust	O
+reduction	O
+in	O
+neurogenesis	O
+,	O
+but	O
+does	O
+not	O
+disturb	O
+granule	O
+neuron	O
+maturation	O
+per	O
+se	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+role	O
+of	O
+Ngn2	O
+is	O
+to	O
+maintain	O
+progenitors	O
+in	O
+an	O
+undifferentiated	O
+state	O
+,	O
+allowing	O
+them	O
+to	O
+amplify	O
+prior	O
+to	O
+their	O
+maturation	O
+into	O
+granule	O
+neurons	O
+upon	O
+NeuroD1	O
+induction	O
+.	O
+
+When	O
+we	O
+overexpressed	O
+Ngn2	O
+and	O
+NeuroD1	O
+in	O
+vivo	O
+,	O
+we	O
+found	O
+NeuroD1	O
+to	O
+exhibit	O
+a	O
+more	O
+pronounced	O
+neuron	O
+-	O
+inductive	O
+effect	O
+,	O
+leading	O
+to	O
+granule	O
+neuron	O
+commitment	O
+,	O
+than	O
+that	O
+displayed	O
+by	O
+Ngn2	O
+.	O
+
+Finally	O
+,	O
+we	O
+observed	O
+that	O
+all	O
+markers	O
+expressed	O
+during	O
+the	O
+transcriptional	O
+control	O
+of	O
+hippocampal	O
+neurogenesis	O
+in	O
+rodents	O
+are	O
+also	O
+present	O
+in	O
+the	O
+human	B
+hippocampus	O
+.	O
+
+Taken	O
+together	O
+,	O
+we	O
+demonstrate	O
+a	O
+critical	O
+role	O
+of	O
+for	O
+Ngn2	O
+and	O
+NeuroD1	O
+in	O
+controlling	O
+neuronal	O
+commitment	O
+and	O
+hippocampal	O
+granule	O
+neuroblast	O
+formation	O
+,	O
+both	O
+during	O
+embryonic	O
+development	O
+and	O
+in	O
+post	O
+-	O
+natal	O
+hippocampal	O
+granule	O
+neurogenesis	O
+.	O
+
+Introduction	O
+
+Neurons	O
+are	O
+born	O
+not	O
+only	O
+during	O
+development	O
+of	O
+the	O
+central	O
+nervous	O
+system	O
+,	O
+but	O
+neurogenesis	O
+also	O
+continues	O
+into	O
+adulthood	O
+.	O
+
+In	O
+both	O
+rodent	B
+and	O
+human	B
+adult	O
+brain	O
+,	O
+neurogenesis	O
+is	O
+active	O
+in	O
+two	O
+distinct	O
+zones	O
+of	O
+the	O
+forebrain	O
+:	O
+the	O
+subventricular	O
+zone	O
+(	O
+SVZ	O
+)	O
+of	O
+the	O
+lateral	O
+ventricle	O
+and	O
+the	O
+subgranular	O
+zone	O
+(	O
+SGZ	O
+)	O
+of	O
+the	O
+hippocampal	O
+dentate	O
+gyrus	O
+(	O
+DG	O
+)	O
+[	O
+1	O
+]	O
+-	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+molecular	O
+mechanism	O
+underlying	O
+neurogenesis	O
+in	O
+the	O
+DG	O
+is	O
+not	O
+fully	O
+understood	O
+.	O
+
+Clearly	O
+,	O
+a	O
+cascade	O
+of	O
+transcriptional	O
+events	O
+controls	O
+the	O
+specification	O
+of	O
+neuronal	O
+identity	O
+in	O
+the	O
+DG	O
+[	O
+3	O
+]	O
+,	O
+[	O
+6	O
+]	O
+-	O
+[	O
+8	O
+]	O
+,	O
+but	O
+details	O
+of	O
+the	O
+expression	O
+pattern	O
+and	O
+function	O
+of	O
+each	O
+transcription	O
+factor	O
+remain	O
+elusive	O
+.	O
+
+The	O
+paired	O
+-	O
+box	O
+homeodomain	O
+transcription	O
+factor	O
+Pax6	O
+and	O
+the	O
+bHLH	O
+transcription	O
+factors	O
+Ngn2	O
+and	O
+NeuroD1	O
+are	O
+important	O
+when	O
+cells	O
+acquire	O
+a	O
+pan	O
+-	O
+neuronal	O
+character	O
+and	O
+a	O
+specific	O
+neuronal	O
+subtype	O
+[	O
+9	O
+]	O
+,	O
+[	O
+10	O
+]	O
+.	O
+
+In	O
+the	O
+developing	O
+neocortex	O
+,	O
+Pax6	O
+is	O
+expressed	O
+in	O
+dividing	O
+radial	O
+glial	O
+cells	O
+at	O
+the	O
+ventricular	O
+surface	O
+[	O
+9	O
+]	O
+.	O
+
+In	O
+the	O
+adult	O
+hippocampus	O
+,	O
+Pax6	O
+is	O
+expressed	O
+in	O
+astrocytes	O
+in	O
+the	O
+SGZ	O
+and	O
+are	O
+considered	O
+to	O
+be	O
+the	O
+true	O
+stem	O
+cells	O
+[	O
+9	O
+]	O
+,	O
+[	O
+11	O
+]	O
+.	O
+
+Loss	O
+-	O
+and	O
+gain	O
+-	O
+of	O
+-	O
+function	O
+studies	O
+indicate	O
+that	O
+Pax6	O
+is	O
+involved	O
+in	O
+regulating	O
+the	O
+proliferation	O
+of	O
+neocortical	O
+and	O
+hippocampal	O
+progenitors	O
+[	O
+9	O
+]	O
+,	O
+[	O
+12	O
+]	O
+-	O
+[	O
+16	O
+]	O
+.	O
+
+During	O
+neocorticogenesis	O
+,	O
+high	O
+concentrations	O
+of	O
+Pax6	O
+induce	O
+the	O
+expression	O
+of	O
+the	O
+bHLH	O
+transcription	O
+factor	O
+Neurogenin2	O
+(	O
+Ngn2	O
+)	O
+[	O
+17	O
+]	O
+.	O
+
+In	O
+turn	O
+,	O
+Ngn2	O
+causes	O
+cell	O
+cycle	O
+exit	O
+[	O
+18	O
+]	O
+,	O
+an	O
+event	O
+that	O
+takes	O
+place	O
+when	O
+NeuroD1	O
+starts	O
+to	O
+be	O
+expressed	O
+[	O
+19	O
+]	O
+.	O
+
+In	O
+the	O
+developing	O
+hippocampus	O
+,	O
+the	O
+absence	O
+of	O
+Ngn2	O
+leads	O
+to	O
+a	O
+reduced	O
+number	O
+of	O
+granule	O
+neurons	O
+[	O
+20	O
+]	O
+.	O
+
+NeuroD1	O
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+is	O
+essential	O
+for	O
+the	O
+differentiation	O
+and	O
+survival	O
+of	O
+hippocampal	O
+granule	O
+neurons	O
+[	O
+10	O
+]	O
+.	O
+
+Interestingly	O
+,	O
+in	O
+the	O
+absence	O
+of	O
+Ngn2	O
+,	O
+NeuroD1	O
+can	O
+still	O
+be	O
+activated	O
+and	O
+neuronal	O
+differentiation	O
+can	O
+still	O
+take	O
+place	O
+[	O
+20	O
+]	O
+.	O
+
+This	O
+has	O
+led	O
+to	O
+the	O
+idea	O
+that	O
+the	O
+primary	O
+role	O
+of	O
+Ngn2	O
+is	O
+not	O
+to	O
+direct	O
+neuronal	O
+differentiation	O
+.	O
+
+Only	O
+a	O
+small	O
+number	O
+of	O
+studies	O
+have	O
+addressed	O
+the	O
+role	O
+of	O
+Ngn2	O
+and	O
+NeuroD1	O
+in	O
+hippocampal	O
+neurogenesis	O
+[	O
+10	O
+]	O
+,	O
+[	O
+20	O
+]	O
+,	O
+[	O
+21	O
+]	O
+.	O
+
+Therefore	O
+,	O
+we	O
+now	O
+re	O
+-	O
+examine	O
+their	O
+roles	O
+in	O
+hippocampal	O
+neurogenesis	O
+in	O
+detail	O
+,	O
+using	O
+gain	O
+-	O
+and	O
+loss	O
+-	O
+of	O
+-	O
+function	O
+experiments	O
+.	O
+
+We	O
+first	O
+establish	O
+a	O
+hierarchy	O
+of	O
+transcriptional	O
+events	O
+that	O
+occur	O
+during	O
+neurogenesis	O
+in	O
+the	O
+DG	O
+and	O
+then	O
+define	O
+the	O
+place	O
+that	O
+Ngn2	O
+,	O
+NeuroD1	O
+and	O
+other	O
+transcription	O
+factors	O
+have	O
+in	O
+this	O
+cascade	O
+.	O
+
+We	O
+find	O
+that	O
+a	O
+lack	O
+of	O
+Ngn2	O
+expression	O
+result	O
+in	O
+a	O
+markedly	O
+smaller	O
+hippocampus	O
+and	O
+an	O
+almost	O
+complete	O
+absence	O
+of	O
+the	O
+DG	O
+.	O
+
+We	O
+show	O
+that	O
+Ngn2	O
+is	O
+required	O
+for	O
+granule	O
+neuroblasts	O
+production	O
+/	O
+amplification	O
+.	O
+
+Gain	O
+-	O
+of	O
+-	O
+function	O
+of	O
+NeuroD1	O
+during	O
+development	O
+of	O
+the	O
+DG	O
+results	O
+in	O
+an	O
+efficient	O
+generation	O
+of	O
+granule	O
+neuroblasts	O
+,	O
+an	O
+effect	O
+that	O
+we	O
+do	O
+not	O
+observe	O
+when	O
+we	O
+overexpress	O
+Ngn2	O
+.	O
+
+Finally	O
+,	O
+we	O
+demonstrate	O
+that	O
+the	O
+same	O
+transcription	O
+factors	O
+and	O
+cellular	O
+markers	O
+seen	O
+in	O
+mouse	B
+and	O
+rat	B
+tissue	O
+are	O
+also	O
+present	O
+in	O
+the	O
+human	B
+hippocampus	O
+.	O
+
+Results	O
+
+Expression	O
+of	O
+transcription	O
+factors	O
+and	O
+cellular	O
+markers	O
+define	O
+different	O
+phases	O
+of	O
+postnatal	O
+hippocampal	O
+granule	O
+neuron	O
+maturation	O
+
+We	O
+first	O
+analyzed	O
+in	O
+detail	O
+the	O
+chronology	O
+of	O
+expression	O
+of	O
+different	O
+transcription	O
+factors	O
+and	O
+cell	O
+-	O
+specific	O
+markers	O
+during	O
+DG	O
+granule	O
+neuron	O
+formation	O
+and	O
+correlated	O
+our	O
+findings	O
+to	O
+the	O
+previously	O
+established	O
+classification	O
+of	O
+adult	O
+hippocampal	O
+neurogenesis	O
+[	O
+3	O
+]	O
+.	O
+
+The	O
+current	O
+classification	O
+describes	O
+hippocampal	O
+stem	O
+cells	O
+and	O
+progenies	O
+into	O
+three	O
+categories	O
+(	O
+type	O
+-	O
+1	O
+,	O
+-	O
+2	O
+and	O
+-	O
+3	O
+cells	O
+)	O
+depending	O
+on	O
+the	O
+markers	O
+they	O
+express	O
+as	O
+they	O
+mature	O
+.	O
+
+In	O
+the	O
+adult	O
+mouse	B
+DG	O
+,	O
+only	O
+a	O
+very	O
+small	O
+proportion	O
+of	O
+cells	O
+undergo	O
+mitosis	O
+at	O
+any	O
+one	O
+given	O
+time	O
+[	O
+22	O
+]	O
+.	O
+
+Consequently	O
+,	O
+in	O
+adult	O
+animals	O
+it	O
+is	O
+difficult	O
+to	O
+analyze	O
+which	O
+transcription	O
+factors	O
+are	O
+involved	O
+in	O
+the	O
+transition	O
+phase	O
+from	O
+one	O
+cell	O
+category	O
+to	O
+the	O
+next	O
+.	O
+
+Therefore	O
+,	O
+we	O
+studied	O
+2	O
+week	O
+-	O
+old	O
+rodents	O
+which	O
+have	O
+higher	O
+numbers	O
+of	O
+maturing	O
+granule	O
+neurons	O
+in	O
+the	O
+DG	O
+.	O
+
+We	O
+performed	O
+triple	O
+immunohistochemistry	O
+for	O
+all	O
+markers	O
+of	O
+interest	O
+and	O
+compared	O
+results	O
+from	O
+2	O
+week	O
+-	O
+and	O
+2	O
+month	O
+-	O
+old	O
+mice	B
+(	O
+Figure	O
+1	O
+and	O
+figure	O
+S1	O
+)	O
+.	O
+
+We	O
+first	O
+confirmed	O
+that	O
+stem	O
+cells	O
+in	O
+the	O
+SGZ	O
+exhibit	O
+characteristics	O
+of	O
+radial	O
+glia	O
+[	O
+3	O
+]	O
+,	O
+[	O
+11	O
+]	O
+,	O
+[	O
+16	O
+]	O
+.	O
+
+They	O
+extend	O
+radial	O
+processes	O
+from	O
+the	O
+SGZ	O
+to	O
+the	O
+apex	O
+of	O
+the	O
+subgranular	O
+layer	O
+(	O
+SGL	O
+)	O
+and	O
+the	O
+basal	O
+molecular	O
+layer	O
+.	O
+
+Moreover	O
+,	O
+they	O
+express	O
+the	O
+intermediate	O
+filament	O
+protein	O
+nestin	O
+,	O
+glial	O
+fibrillary	O
+acidic	O
+protein	O
+(	O
+GFAP	O
+)	O
+and	O
+glial	O
+glutamate	O
+transporter	O
+(	O
+GLAST	O
+)	O
+[	O
+16	O
+]	O
+(	O
+Figure	O
+1A	O
+and	O
+B	O
+and	O
+figure	O
+S1A	O
+and	O
+S1B	O
+)	O
+.	O
+
+The	O
+GFAP	O
+-	O
+and	O
+GLAST	O
++	O
+cells	O
+are	O
+defined	O
+as	O
+type	O
+-	O
+1	O
+cells	O
+[	O
+3	O
+]	O
+.	O
+
+They	O
+also	O
+express	O
+the	O
+paired	O
+-	O
+homeodomain	O
+transcription	O
+factor	O
+Pax6	O
+(	O
+Figure	O
+1B	O
+)	O
+.	O
+
+These	O
+radial	O
+glia	O
+-	O
+like	O
+stem	O
+cells	O
+divide	O
+relatively	O
+infrequently	O
+,	O
+and	O
+are	O
+believed	O
+to	O
+undergo	O
+symmetric	O
+division	O
+(	O
+giving	O
+rise	O
+to	O
+two	O
+identical	O
+stem	O
+cells	O
+)	O
+under	O
+some	O
+conditions	O
+.	O
+
+They	O
+can	O
+also	O
+divide	O
+asymmetrically	O
+and	O
+give	O
+rise	O
+to	O
+a	O
+new	O
+stem	O
+cell	O
+and	O
+one	O
+neuronal	O
+progenitor	O
+,	O
+which	O
+usually	O
+is	O
+defined	O
+as	O
+a	O
+type	O
+-	O
+2	O
+cell	O
+(	O
+Figure	O
+2B	O
+)	O
+[	O
+3	O
+]	O
+.	O
+
+Type	O
+-	O
+2	O
+cells	O
+are	O
+divided	O
+into	O
+two	O
+different	O
+populations	O
+:	O
+type	O
+-	O
+2a	O
+expressing	O
+nestin	O
+and	O
+type	O
+-	O
+2b	O
+co	O
+-	O
+expressing	O
+nestin	O
+and	O
+doublecortin	O
+(	O
+Dcx	O
+)	O
+[	O
+23	O
+]	O
+.	O
+
+Based	O
+on	O
+a	O
+previous	O
+report	O
+[	O
+24	O
+]	O
+,	O
+we	O
+examined	O
+the	O
+expression	O
+pattern	O
+of	O
+the	O
+T	O
+-	O
+domain	O
+transcription	O
+factors	O
+Tbr1	O
+and	O
+Tbr2	O
+.	O
+
+We	O
+found	O
+that	O
+Tbr2	O
+is	O
+expressed	O
+in	O
+type	O
+-	O
+2a	O
+cells	O
+,	O
+in	O
+agreement	O
+with	O
+a	O
+recent	O
+report	O
+[	O
+25	O
+]	O
+.	O
+
+In	O
+the	O
+SGZ	O
+of	O
+2	O
+week	O
+-	O
+old	O
+mice	B
+,	O
+we	O
+found	O
+an	O
+average	O
+of	O
+50	O
+-	O
+70	O
+Tbr2	O
++	O
+cells	O
+per	O
+30	O
+micro	O
+m	O
+-	O
+thick	O
+section	O
+throughout	O
+the	O
+rostro	O
+-	O
+caudal	O
+axis	O
+of	O
+the	O
+dorsal	O
+hippocampus	O
+.	O
+
+This	O
+number	O
+was	O
+reduced	O
+by	O
+35	O
+%	O
+in	O
+2	O
+month	O
+-	O
+old	O
+mice	B
+(	O
+Figure	O
+1C	O
+with	O
+figure	O
+S1C	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+As	O
+opposed	O
+to	O
+Tbr1	O
+(	O
+Figure	O
+1D	O
+and	O
+figure	O
+S1D	O
+)	O
+,	O
+Tbr2	O
++	O
+cells	O
+did	O
+not	O
+co	O
+-	O
+express	O
+Dcx	O
+or	O
+PSA	O
+-	O
+NCAM	O
+(	O
+Figure	O
+1C	O
+and	O
+figure	O
+S1C	O
+)	O
+.	O
+
+We	O
+observed	O
+that	O
+Tbr1	O
+-	O
+immuoreactivity	O
+gradually	O
+decreased	O
+as	O
+neurons	O
+matured	O
+and	O
+started	O
+to	O
+express	O
+NeuN	O
+(	O
+Figure	O
+1H	O
+and	O
+figure	O
+S1H	O
+)	O
+.	O
+
+Thus	O
+,	O
+Tbr2	O
+labels	O
+type	O
+-	O
+2	O
+cells	O
+,	O
+while	O
+Tbr1	O
+is	O
+expressed	O
+by	O
+immature	O
+granule	O
+neurons	O
+.	O
+
+We	O
+then	O
+examined	O
+the	O
+molecular	O
+phenotype	O
+of	O
+type	O
+-	O
+3	O
+cells	O
+,	O
+a	O
+cell	O
+type	O
+that	O
+transiently	O
+expresses	O
+Calretinin	O
+[	O
+26	O
+]	O
+.	O
+
+We	O
+hypothesized	O
+that	O
+hippocampal	O
+type	O
+-	O
+3	O
+cells	O
+might	O
+also	O
+express	O
+the	O
+bHLH	O
+transcription	O
+factor	O
+NeuroD1	O
+,	O
+known	O
+to	O
+partially	O
+overlap	O
+with	O
+Tbr2	O
+and	O
+Tbr1	O
+in	O
+different	O
+brain	O
+regions	O
+[	O
+24	O
+]	O
+.	O
+
+We	O
+found	O
+that	O
+NeuroD1	O
+expression	O
+in	O
+the	O
+hippocampus	O
+starts	O
+in	O
+Tbr2	O
++	O
+cells	O
+and	O
+extends	O
+to	O
+post	O
+-	O
+mitotic	O
+Tbr1	O
++	O
+cells	O
+,	O
+which	O
+also	O
+express	O
+the	O
+hippocampal	O
+granule	O
+identity	O
+transcription	O
+factor	O
+Prox1	O
+(	O
+Figure	O
+1G	O
+and	O
+1I	O
+and	O
+figure	O
+S1G	O
+and	O
+S1I	O
+)	O
+.	O
+
+While	O
+Tbr1	O
+expression	O
+ceases	O
+during	O
+granule	O
+maturation	O
+,	O
+that	O
+of	O
+NeuroD1	O
+is	O
+weakly	O
+maintained	O
+when	O
+NeuN	O
+expression	O
+starts	O
+(	O
+Figure	O
+1G	O
+and	O
+1H	O
+and	O
+figure	O
+S1G	O
+and	O
+S1H	O
+)	O
+.	O
+
+We	O
+found	O
+that	O
+calretinin	O
+expression	O
+decreased	O
+during	O
+granule	O
+neuron	O
+maturation	O
+,	O
+before	O
+NeuroD1	O
+was	O
+reduced	O
+(	O
+Figure	O
+1F	O
+)	O
+.	O
+
+Thus	O
+NeuroD1	O
+is	O
+expressed	O
+in	O
+type	O
+-	O
+2b	O
+and	O
+type	O
+-	O
+3	O
+cells	O
+,	O
+as	O
+well	O
+as	O
+immature	O
+granule	O
+neurons	O
+.	O
+
+Finally	O
+,	O
+we	O
+found	O
+that	O
+NeuroD2	O
+starts	O
+to	O
+be	O
+expressed	O
+just	O
+after	O
+NeuroD1	O
+and	O
+,	O
+unlike	O
+NeuroD1	O
+,	O
+continues	O
+to	O
+be	O
+highly	O
+expressed	O
+in	O
+mature	O
+neurons	O
+(	O
+Figure	O
+1J	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Mash1	O
+and	O
+Ngn2	O
+define	O
+the	O
+early	O
+versus	O
+late	O
+type	O
+-	O
+2a	O
+stage	O
+in	O
+2	O
+weeks	O
+old	O
+mice	B
+
+Having	O
+established	O
+the	O
+hierarchy	O
+of	O
+transcription	O
+factors	O
+and	O
+cellular	O
+markers	O
+appearing	O
+during	O
+hippocampal	O
+neurogenesis	O
+,	O
+we	O
+set	O
+out	O
+to	O
+clarify	O
+the	O
+position	O
+of	O
+the	O
+two	O
+bHLH	O
+transcription	O
+factors	O
+Ngn2	O
+and	O
+Mash1	O
+,	O
+in	O
+this	O
+process	O
+.	O
+
+We	O
+found	O
+that	O
+more	O
+than	O
+90	O
+%	O
+of	O
+Ngn2	O
+-	O
+immunoreactive	O
+cells	O
+are	O
+Pax6	O
+positive	O
+(	O
+Figure	O
+2A	O
+)	O
+,	O
+and	O
+almost	O
+all	O
+co	O
+-	O
+express	O
+Tbr2	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+Thus	O
+,	O
+Ngn2	O
+appears	O
+to	O
+be	O
+expressed	O
+by	O
+type	O
+-	O
+2a	O
+cells	O
+.	O
+
+As	O
+our	O
+antibodies	O
+against	O
+Ngn2	O
+and	O
+NeuroD1	O
+were	O
+made	O
+in	O
+the	O
+same	O
+species	O
+,	O
+we	O
+could	O
+not	O
+determine	O
+if	O
+there	O
+was	O
+an	O
+overlap	O
+between	O
+these	O
+two	O
+proteins	O
+.	O
+
+However	O
+,	O
+by	O
+comparing	O
+their	O
+overlapping	O
+expression	O
+pattern	O
+with	O
+that	O
+of	O
+Tbr2	O
+,	O
+we	O
+propose	O
+that	O
+some	O
+Ngn2	O
++	O
+cells	O
+co	O
+-	O
+express	O
+NeuroD1	O
+,	O
+and	O
+that	O
+they	O
+appear	O
+at	O
+the	O
+onset	O
+of	O
+NeuroD1	O
+expression	O
+and	O
+downregulation	O
+of	O
+Ngn2	O
+.	O
+
+We	O
+base	O
+this	O
+assumption	O
+on	O
+the	O
+facts	O
+that	O
+more	O
+than	O
+50	O
+%	O
+of	O
+the	O
+Tbr2	O
++	O
+cells	O
+are	O
+Ngn2	O
++	O
+and	O
+more	O
+than	O
+50	O
+%	O
+of	O
+Tbr2	O
++	O
+cells	O
+also	O
+express	O
+NeuroD1	O
+.	O
+
+The	O
+expression	O
+of	O
+Ngn2	O
+in	O
+adult	O
+hippocampus	O
+was	O
+hard	O
+to	O
+detect	O
+using	O
+immunohistochemistry	O
+due	O
+to	O
+the	O
+low	O
+expression	O
+of	O
+the	O
+protein	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+present	O
+,	O
+as	O
+previously	O
+described	O
+using	O
+reporter	O
+mice	B
+and	O
+as	O
+revealed	O
+by	O
+in	O
+situ	O
+hybridization	O
+[	O
+21	O
+]	O
+.	O
+
+We	O
+next	O
+examined	O
+the	O
+expression	O
+of	O
+Mash1	O
+and	O
+compared	O
+it	O
+with	O
+that	O
+of	O
+Ngn2	O
+,	O
+Pax6	O
+and	O
+Tbr2	O
+.	O
+
+We	O
+found	O
+some	O
+Mash1	O
++	O
+cells	O
+(	O
+10	O
+-	O
+20	O
+cells	O
+per	O
+section	O
+)	O
+in	O
+the	O
+dorsal	O
+hippocampus	O
+.	O
+
+Almost	O
+all	O
+of	O
+them	O
+co	O
+-	O
+expressed	O
+Pax6	O
+(	O
+Figure	O
+2C	O
+)	O
+.	O
+
+Only	O
+few	O
+cells	O
+co	O
+-	O
+expressed	O
+Tbr2	O
+(	O
+Figure	O
+2D	O
+)	O
+or	O
+Ngn2	O
+(	O
+Figure	O
+2E	O
+)	O
+,	O
+suggesting	O
+that	O
+Mash1	O
+is	O
+downregulated	O
+when	O
+these	O
+two	O
+proteins	O
+are	O
+expressed	O
+.	O
+
+None	O
+of	O
+the	O
+Mash1	O
+-	O
+expressing	O
+cells	O
+were	O
+positive	O
+for	O
+NeuroD1	O
+(	O
+Figure	O
+2F	O
+)	O
+.	O
+
+Mash1	O
++	O
+cells	O
+were	O
+still	O
+undergoing	O
+mitosis	O
+(	O
+Figure	O
+2C	O
+)	O
+and	O
+consequently	O
+over	O
+90	O
+%	O
+of	O
+them	O
+co	O
+-	O
+labeled	O
+with	O
+the	O
+cell	O
+-	O
+cycle	O
+marker	O
+Ki67	O
+(	O
+Figure	O
+S1J	O
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+we	O
+show	O
+that	O
+Mash1	O
+and	O
+Ngn2	O
+are	O
+expressed	O
+in	O
+early	O
+and	O
+late	O
+stages	O
+of	O
+maturation	O
+of	O
+type2a	O
+progenitors	O
+,	O
+respectively	O
+,	O
+and	O
+that	O
+both	O
+transcription	O
+factors	O
+are	O
+co	O
+-	O
+expressed	O
+briefly	O
+when	O
+cells	O
+transit	O
+from	O
+early	O
+to	O
+late	O
+phase	O
+type2a	O
+cells	O
+.	O
+
+Ngn2	O
+progenies	O
+become	O
+hippocampal	O
+granule	O
+neurons	O
+
+Previous	O
+work	O
+has	O
+shown	O
+that	O
+in	O
+Mash1	O
+null	O
+mutant	O
+mice	B
+hippocampal	O
+neurogenesis	O
+is	O
+not	O
+reduced	O
+and	O
+the	O
+hippocampus	O
+is	O
+not	O
+malformed	O
+[	O
+20	O
+]	O
+.	O
+
+Therefore	O
+we	O
+focused	O
+our	O
+initial	O
+analysis	O
+on	O
+the	O
+role	O
+of	O
+Ngn2	O
+in	O
+hippocampal	O
+neurogenesis	O
+.	O
+
+We	O
+characterized	O
+the	O
+fate	O
+of	O
+Ngn2	O
+-	O
+expressing	O
+cells	O
+using	O
+Ngn2	O
+Knock	O
+-	O
+in	O
+green	O
+fluorescent	O
+protein	O
+(	O
+GFP	O
+)	O
+mice	B
+(	O
+Ngn2	O
++	O
+/	O
+GFP	O
+)	O
+[	O
+27	O
+]	O
+.	O
+
+In	O
+the	O
+SGZ	O
+of	O
+2	O
+week	O
+-	O
+old	O
+hippocampi	O
+,	O
+we	O
+found	O
+bright	O
+GFP	O
+-	O
+expressing	O
+cells	O
+that	O
+were	O
+positive	O
+for	O
+Tbr2	O
+(	O
+Figure	O
+2H	O
+)	O
+,	O
+the	O
+immature	O
+neuronal	O
+marker	O
+PSA	O
+-	O
+NCAM	O
+(	O
+Figure	O
+2I	O
+)	O
+and	O
+NeuroD1	O
+(	O
+Figure	O
+2J	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+Prox1	O
++	O
+,	O
+NeuroD2	O
++	O
+and	O
+calretinin	O
++	O
+cells	O
+were	O
+also	O
+weakly	O
+positive	O
+for	O
+GFP	O
+.	O
+
+We	O
+made	O
+similar	O
+observations	O
+in	O
+2	O
+month	O
+-	O
+old	O
+mice	B
+(	O
+data	O
+not	O
+shown	O
+)	O
+confirming	O
+earlier	O
+published	O
+results	O
+[	O
+21	O
+]	O
+)	O
+.	O
+
+We	O
+did	O
+not	O
+observe	O
+Mash1	O
++	O
+/	O
+GFP	O
++	O
+and	O
+NeuN	O
++	O
+/	O
+GFP	O
++	O
+cells	O
+(	O
+Figure	O
+2G	O
+)	O
+.	O
+
+These	O
+data	O
+from	O
+Ngn2	O
++	O
+/	O
+GFP	O
+mice	B
+are	O
+entirely	O
+consistent	O
+with	O
+our	O
+earlier	O
+observations	O
+using	O
+immunocytochemistry	O
+to	O
+label	O
+Ngn2	O
+-	O
+expressing	O
+cells	O
+and	O
+with	O
+GFP	O
+undergoing	O
+slow	O
+degradation	O
+after	O
+the	O
+expression	O
+of	O
+Ngn2	O
+has	O
+ceased	O
+.	O
+
+Importantly	O
+,	O
+none	O
+of	O
+the	O
+GFP	O
+-	O
+expressing	O
+cells	O
+,	O
+including	O
+those	O
+only	O
+weakly	O
+fluorescent	O
+,	O
+residing	O
+in	O
+the	O
+SGL	O
+expressed	O
+the	O
+astrocytic	O
+marker	O
+GFAP	O
+or	O
+the	O
+oligodendrocytic	O
+markers	O
+CNPase	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+data	O
+show	O
+that	O
+Ngn2	O
+progenies	O
+become	O
+neurons	O
+and	O
+never	O
+generate	O
+astrocytes	O
+or	O
+oligodendrocytes	O
+.	O
+
+Marked	O
+reduction	O
+of	O
+hippocampal	O
+granule	O
+neurons	O
+in	O
+absence	O
+of	O
+Ngn2	O
+
+To	O
+determine	O
+the	O
+role	O
+of	O
+Ngn2	O
+during	O
+the	O
+initiation	O
+of	O
+hippocampal	O
+granule	O
+neurogenesis	O
+,	O
+we	O
+analyzed	O
+the	O
+hippocampus	O
+of	O
+mice	B
+lacking	O
+Ngn2	O
+(	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+mice	B
+use	O
+by	O
+Galichet	O
+and	O
+coworkers	O
+,	O
+our	O
+mice	B
+have	O
+a	O
+lifespan	O
+of	O
+only	O
+2	O
+weeks	O
+after	O
+birth	O
+.	O
+
+Therefore	O
+,	O
+we	O
+analyzed	O
+2	O
+week	O
+-	O
+old	O
+and	O
+younger	O
+mice	B
+.	O
+
+Consistent	O
+with	O
+previous	O
+observations	O
+[	O
+20	O
+]	O
+,	O
+the	O
+hippocampus	O
+in	O
+Ngn2GFP	O
+/	O
+GFP	O
+mutants	O
+is	O
+clearly	O
+malformed	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+In	O
+two	O
+week	O
+-	O
+old	O
+Ngn2GFP	O
+/	O
+GFP	O
+mice	B
+,	O
+the	O
+ventral	O
+blade	O
+of	O
+the	O
+DG	O
+is	O
+completely	O
+absent	O
+.	O
+
+Already	O
+on	O
+postnatal	O
+day	O
+1	O
+-	O
+2	O
+,	O
+the	O
+ventral	O
+blade	O
+of	O
+the	O
+DG	O
+is	O
+malformed	O
+along	O
+its	O
+whole	O
+rostro	O
+-	O
+caudal	O
+axis	O
+(	O
+Figure	O
+3B	O
+)	O
+.	O
+
+As	O
+neither	O
+migration	O
+defects	O
+nor	O
+cell	O
+death	O
+cause	O
+the	O
+reduced	O
+number	O
+of	O
+hippocampal	O
+neurons	O
+in	O
+Ngn2	O
+null	O
+mice	B
+[	O
+20	O
+]	O
+,	O
+we	O
+asked	O
+if	O
+Ngn2	O
+is	O
+necessary	O
+for	O
+production	O
+of	O
+hippocampal	O
+granule	O
+neuroblasts	O
+.	O
+
+We	O
+first	O
+injected	O
+2	O
+day	O
+-	O
+old	O
+mouse	B
+pups	O
+with	O
+BrdU	O
+2	O
+hours	O
+prior	O
+to	O
+sacrifice	O
+,	O
+allowing	O
+us	O
+to	O
+evaluate	O
+cell	O
+proliferation	O
+and	O
+ongoing	O
+neurogenesis	O
+.	O
+
+We	O
+also	O
+injected	O
+BrdU	O
+into	O
+female	O
+mice	B
+on	O
+their	O
+final	O
+day	O
+of	O
+pregnancy	O
+and	O
+examined	O
+the	O
+brains	O
+of	O
+their	O
+pups	O
+48	O
+hours	O
+later	O
+(	O
+corresponding	O
+to	O
+P1	O
+-	O
+P2	O
+old	O
+pups	O
+)	O
+.	O
+
+This	O
+allowed	O
+us	O
+to	O
+assess	O
+the	O
+number	O
+of	O
+neurons	O
+derived	O
+from	O
+the	O
+last	O
+day	O
+of	O
+intrauterine	O
+development	O
+.	O
+
+Regardless	O
+of	O
+whether	O
+the	O
+mice	B
+were	O
+WT	O
+or	O
+hetero	O
+/	O
+homozygous	O
+mutant	O
+pups	O
+,	O
+we	O
+found	O
+cells	O
+that	O
+had	O
+incorporated	O
+BrdU	O
+in	O
+the	O
+hippocampal	O
+subventricular	O
+zone	O
+(	O
+hSVZ	O
+)	O
+,	O
+fimbria	O
+and	O
+the	O
+DG	O
+(	O
+Figure	O
+4A	O
+and	O
+B	O
+;	O
+[	O
+28	O
+]	O
+)	O
+,	O
+suggesting	O
+that	O
+progenitors	O
+originating	O
+in	O
+the	O
+hSVZ	O
+divide	O
+while	O
+migrating	O
+towards	O
+the	O
+DG	O
+.	O
+
+Most	O
+of	O
+them	O
+were	O
+organized	O
+in	O
+chains	O
+typical	O
+of	O
+migrating	O
+cells	O
+(	O
+Figure	O
+4A	O
+and	O
+B	O
+and	O
+figure	O
+S2	O
+)	O
+.	O
+
+In	O
+Ngn2GFP	O
+/	O
+GFP	O
+mutant	O
+mice	B
+injected	O
+with	O
+BrdU	O
+2	O
+hours	O
+prior	O
+to	O
+sacrifice	O
+,	O
+we	O
+observed	O
+a	O
+decrease	O
+in	O
+the	O
+number	O
+of	O
+BrdU	O
++	O
+cells	O
+compared	O
+to	O
+heterozygous	O
+littermates	O
+.	O
+
+Thus	O
+,	O
+the	O
+numbers	O
+of	O
+newborn	O
+cells	O
+were	O
+reduced	O
+in	O
+the	O
+hSVZ	O
+/	O
+fimbria	O
+(	O
+133	O
+.	O
+3	O
++	O
+/	O
+-	O
+7	O
+.	O
+5	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+69	O
+.	O
+7	O
++	O
+/	O
+-	O
+5	O
+.	O
+0	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+and	O
+DG	O
+(	O
+132	O
+.	O
+0	O
++	O
+/	O
+-	O
+9	O
+.	O
+1	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+42	O
+.	O
+6	O
++	O
+/	O
+-	O
+2	O
+.	O
+2	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+(	O
+Figure	O
+4C	O
+and	O
+D	O
+)	O
+.	O
+
+We	O
+also	O
+examined	O
+the	O
+number	O
+of	O
+newborn	O
+cells	O
+differentiating	O
+into	O
+neurons	O
+,	O
+and	O
+identified	O
+them	O
+by	O
+the	O
+co	O
+-	O
+expression	O
+of	O
+BrdU	O
+and	O
+NeuroD1	O
+.	O
+
+As	O
+expected	O
+,	O
+they	O
+were	O
+relatively	O
+few	O
+in	O
+numbers	O
+because	O
+the	O
+short	O
+delay	O
+(	O
+2	O
+hours	O
+)	O
+between	O
+BrdU	O
+administration	O
+and	O
+sacrifice	O
+in	O
+this	O
+first	O
+experimental	O
+paradigm	O
+.	O
+
+In	O
+Ngn2GFP	O
+/	O
+GFP	O
+null	O
+mutants	O
+,	O
+we	O
+found	O
+the	O
+number	O
+of	O
+cells	O
+differentiating	O
+into	O
+neurons	O
+to	O
+be	O
+reduced	O
+by	O
+60	O
+%	O
+and	O
+71	O
+%	O
+in	O
+the	O
+hSVZ	O
+/	O
+fimbria	O
+(	O
+8	O
+.	O
+6	O
++	O
+/	O
+-	O
+1	O
+.	O
+4	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+3	O
+.	O
+4	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+and	O
+DG	O
+(	O
+9	O
+.	O
+7	O
++	O
+/	O
+-	O
+1	O
+.	O
+1	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+2	O
+.	O
+8	O
++	O
+/	O
+-	O
+0	O
+.	O
+6	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+,	O
+respectively	O
+,	O
+(	O
+Figure	O
+4E	O
+and	O
+F	O
+)	O
+.	O
+
+As	O
+a	O
+result	O
+,	O
+the	O
+number	O
+of	O
+NeuroD1	O
++	O
+cells	O
+in	O
+the	O
+DG	O
+was	O
+reduced	O
+by	O
+80	O
+%	O
+(	O
+580	O
+.	O
+3	O
++	O
+/	O
+-	O
+27	O
+.	O
+7	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+116	O
+.	O
+2	O
++	O
+/	O
+-	O
+7	O
+.	O
+3	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+;	O
+Figure	O
+4G	O
+)	O
+.	O
+
+We	O
+obtained	O
+similar	O
+results	O
+in	O
+the	O
+second	O
+paradigm	O
+,	O
+i	O
+.	O
+e	O
+.	O
+in	O
+mice	B
+that	O
+we	O
+sacrificed	O
+48	O
+hours	O
+after	O
+BrdU	O
+administration	O
+and	O
+in	O
+which	O
+a	O
+larger	O
+number	O
+of	O
+the	O
+newborn	O
+cells	O
+had	O
+time	O
+to	O
+mature	O
+into	O
+neurons	O
+.	O
+
+In	O
+this	O
+case	O
+,	O
+the	O
+number	O
+of	O
+BrdU	O
++	O
+/	O
+NeuroD1	O
++	O
+cells	O
+in	O
+the	O
+DG	O
+was	O
+reduced	O
+by	O
+73	O
+%	O
+of	O
+Ngn2GFP	O
+/	O
+GFP	O
+mutant	O
+animals	O
+(	O
+91	O
+.	O
+5	O
++	O
+/	O
+-	O
+24	O
+.	O
+1	O
+for	O
+Ngn2	O
++	O
+/	O
+GFP	O
+vs	O
+26	O
+.	O
+4	O
++	O
+/	O
+-	O
+3	O
+.	O
+3	O
+for	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+(	O
+Figure	O
+4J	O
+)	O
+.	O
+
+We	O
+found	O
+no	O
+differences	O
+in	O
+the	O
+proportion	O
+of	O
+BrdU	O
++	O
+cells	O
+that	O
+expressed	O
+NeuroD1	O
+in	O
+Ngn2	O
++	O
+/	O
+GFP	O
+and	O
+Ngn2GFP	O
+/	O
+GFP	O
+mice	B
+(	O
+14	O
+.	O
+2	O
++	O
+/	O
+-	O
+1	O
+.	O
+0	O
+%	O
+and	O
+17	O
+.	O
+4	O
++	O
+/	O
+-	O
+1	O
+.	O
+8	O
+%	O
+respectively	O
+;	O
+Figure	O
+4K	O
+)	O
+.	O
+
+This	O
+shows	O
+that	O
+the	O
+few	O
+cells	O
+that	O
+manage	O
+to	O
+proliferate	O
+in	O
+the	O
+Ngn2	O
+null	O
+mice	B
+have	O
+the	O
+same	O
+ability	O
+to	O
+differentiate	O
+into	O
+neurons	O
+as	O
+those	O
+in	O
+mice	B
+with	O
+one	O
+Ngn2	O
+allele	O
+.	O
+
+Interestingly	O
+,	O
+the	O
+absence	O
+of	O
+Ngn2	O
+did	O
+not	O
+alter	O
+the	O
+identity	O
+of	O
+neurons	O
+in	O
+the	O
+DG	O
+granule	O
+layer	O
+in	O
+2	O
+week	O
+-	O
+old	O
+Ngn2	O
+null	O
+mice	B
+.	O
+
+The	O
+maturing	O
+granule	O
+progenitors	O
+sequentially	O
+expressed	O
+Pax6	O
+,	O
+Tbr2	O
+(	O
+Figure	O
+S3A	O
+and	O
+S3B	O
+)	O
+,	O
+NeuroD1	O
+and	O
+Calretinin	O
+(	O
+Figure	O
+4L	O
+)	O
+,	O
+PSA	O
+-	O
+NCAM	O
+(	O
+Figure	O
+4N	O
+)	O
+,	O
+Tbr1	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+and	O
+Prox1	O
+(	O
+Figure	O
+4M	O
+)	O
+.	O
+
+We	O
+confirmed	O
+that	O
+the	O
+same	O
+transcriptional	O
+cascade	O
+is	O
+active	O
+in	O
+the	O
+20	O
+%	O
+(	O
+compared	O
+to	O
+mice	B
+with	O
+one	O
+Ngn2	O
+allele	O
+)	O
+residual	O
+granule	O
+neurons	O
+that	O
+are	O
+formed	O
+two	O
+day	O
+-	O
+old	O
+in	O
+Ngn2GFP	O
+/	O
+GFP	O
+mice	B
+(	O
+Figure	O
+S3D	O
+-	O
+G	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+We	O
+next	O
+investigated	O
+if	O
+the	O
+cells	O
+that	O
+failed	O
+to	O
+develop	O
+into	O
+neurons	O
+in	O
+Ngn2GFP	O
+/	O
+GFP	O
+mutant	O
+mice	B
+,	O
+became	O
+glial	O
+cells	O
+.	O
+
+We	O
+found	O
+that	O
+cells	O
+expressing	O
+GFP	O
+never	O
+co	O
+-	O
+labeled	O
+with	O
+the	O
+astrocyte	O
+marker	O
+GFAP	O
+(	O
+Figure	O
+4N	O
+)	O
+or	O
+the	O
+oligodendrocyte	O
+marker	O
+CNPase	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Altogether	O
+,	O
+our	O
+results	O
+show	O
+that	O
+Ngn2	O
+plays	O
+an	O
+important	O
+role	O
+during	O
+the	O
+production	O
+/	O
+amplification	O
+of	O
+hippocampal	O
+granule	O
+neuroblasts	O
+,	O
+but	O
+not	O
+the	O
+acquisition	O
+of	O
+the	O
+granule	O
+neuron	O
+identity	O
+(	O
+Figure	O
+S7	O
+)	O
+.	O
+
+Ngn2	O
+controls	O
+the	O
+amplification	O
+of	O
+granule	O
+neuron	O
+progenitors	O
+
+We	O
+next	O
+monitored	O
+the	O
+mitogenic	O
+activity	O
+of	O
+Ngn2	O
++	O
+cells	O
+in	O
+the	O
+DG	O
+of	O
+2	O
+week	O
+-	O
+old	O
+WT	O
+mice	B
+.	O
+
+We	O
+observed	O
+that	O
+over	O
+50	O
+%	O
+of	O
+Ngn2	O
++	O
+cells	O
+in	O
+the	O
+DG	O
+of	O
+WT	O
+mice	B
+co	O
+-	O
+expressed	O
+the	O
+mitosis	O
+marker	O
+Ki67	O
+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+Inspired	O
+by	O
+this	O
+finding	O
+,	O
+we	O
+injected	O
+BrdU	O
+into	O
+2	O
+week	O
+-	O
+old	O
+WT	O
+and	O
+Ngn2GFP	O
+/	O
+GFP	O
+mice	B
+and	O
+compared	O
+cell	O
+proliferation	O
+in	O
+the	O
+DG	O
+.	O
+
+We	O
+observed	O
+92	O
+%	O
+reduction	O
+in	O
+number	O
+of	O
+proliferating	O
+cells	O
+in	O
+the	O
+SGZ	O
+of	O
+Ngn2	O
+null	O
+mutant	O
+mice	B
+(	O
+6	O
+.	O
+7	O
++	O
+/	O
+-	O
+0	O
+.	O
+5	O
+)	O
+compared	O
+to	O
+WT	O
+(	O
+83	O
+.	O
+6	O
++	O
+/	O
+-	O
+1	O
+.	O
+2	O
+)	O
+and	O
+heterozygotic	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+littermates	O
+(	O
+Figure	O
+5B	O
+-	O
+C	O
+)	O
+.	O
+
+This	O
+data	O
+confirm	O
+the	O
+importance	O
+of	O
+Ngn2	O
+during	O
+the	O
+amplification	O
+of	O
+granule	O
+progenitor	O
+.	O
+s	O
+.	O
+
+To	O
+further	O
+explore	O
+whether	O
+Ngn2	O
++	O
+cells	O
+become	O
+post	O
+-	O
+mitotic	O
+or	O
+still	O
+proliferate	O
+after	O
+Ngn2	O
+is	O
+downregulated	O
+,	O
+we	O
+performed	O
+immunohistochemistry	O
+on	O
+sections	O
+through	O
+the	O
+DG	O
+of	O
+Ngn2	O
++	O
+/	O
+GFP	O
+mice	B
+.	O
+
+We	O
+stained	O
+them	O
+with	O
+the	O
+mitosis	O
+marker	O
+Phospho	O
+-	O
+histone	O
+3	O
+(	O
+PH3	O
+)	O
+and	O
+NeuroD1	O
+,	O
+which	O
+is	O
+downstream	O
+of	O
+Ngn2	O
+in	O
+the	O
+transcriptional	O
+cascade	O
+controlling	O
+neurogenesis	O
+.	O
+
+Thus	O
+,	O
+in	O
+the	O
+same	O
+sections	O
+we	O
+could	O
+identify	O
+whether	O
+cells	O
+that	O
+had	O
+initiated	O
+Ngn2	O
+expression	O
+(	O
+GFP	O
+labeled	O
+)	O
+,	O
+continued	O
+to	O
+divide	O
+(	O
+PH3	O
++	O
+)	O
+or	O
+committed	O
+to	O
+neuronal	O
+differentiation	O
+(	O
+NeuroD1	O
++	O
+)	O
+.	O
+
+We	O
+observed	O
+some	O
+GFP	O
++	O
+cells	O
+that	O
+co	O
+-	O
+expressed	O
+PH3	O
+.	O
+
+They	O
+all	O
+exhibited	O
+morphological	O
+characteristics	O
+of	O
+one	O
+of	O
+the	O
+five	O
+mitotic	O
+phases	O
+:	O
+prophase	O
+,	O
+metaphase	O
+,	O
+anaphase	O
+,	O
+telophase	O
+and	O
+cytokinesis	O
+(	O
+Figure	O
+5D	O
+and	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Unexpectedly	O
+,	O
+cells	O
+that	O
+colabeled	O
+for	O
+GFP	O
+,	O
+PH3	O
+and	O
+NeuroD1	O
+(	O
+Figure	O
+5E	O
+and	O
+figure	O
+S4A	O
+and	O
+S4B	O
+)	O
+were	O
+rare	O
+.	O
+
+This	O
+indicates	O
+that	O
+Ngn2	O
++	O
+cells	O
+undergo	O
+division	O
+/	O
+amplification	O
+and	O
+that	O
+they	O
+mature	O
+into	O
+post	O
+-	O
+mitotic	O
+neurons	O
+upon	O
+NeuroD1	O
+expression	O
+.	O
+
+In	O
+mice	B
+lacking	O
+Ngn2	O
+,	O
+we	O
+found	O
+the	O
+cells	O
+expressing	O
+GFP	O
+localized	O
+to	O
+the	O
+malformed	O
+ventral	O
+blade	O
+of	O
+the	O
+DG	O
+(	O
+Figure	O
+5F	O
+and	O
+G	O
+)	O
+.	O
+
+All	O
+of	O
+these	O
+cells	O
+were	O
+Ki67	O
++	O
+and	O
+they	O
+only	O
+very	O
+rarely	O
+expressed	O
+PH3	O
+(	O
+Figure	O
+5F	O
+and	O
+G	O
+,	O
+and	O
+figure	O
+S4C	O
+)	O
+in	O
+the	O
+absence	O
+of	O
+Ngn2	O
+most	O
+of	O
+the	O
+cells	O
+are	O
+arrested	O
+in	O
+the	O
+cell	O
+cycle	O
+prior	O
+to	O
+entering	O
+the	O
+M	O
+phase	O
+and	O
+their	O
+mitosis	O
+is	O
+impaired	O
+.	O
+
+These	O
+data	O
+suggest	O
+that	O
+the	O
+mechanism	O
+of	O
+action	O
+of	O
+Ngn2	O
+is	O
+conserved	O
+from	O
+development	O
+of	O
+the	O
+DG	O
+to	O
+postnatal	O
+hippocampal	O
+neurogenesis	O
+.	O
+
+Our	O
+findings	O
+suggest	O
+that	O
+Ngn2	O
+regulates	O
+amplification	O
+and	O
+cell	O
+cycle	O
+exit	O
+of	O
+DG	O
+granule	O
+progenitors	O
+.	O
+
+To	O
+examine	O
+this	O
+hypothesis	O
+,	O
+we	O
+compared	O
+the	O
+effects	O
+of	O
+Ngn2	O
+and	O
+NeuroD1	O
+on	O
+mitotic	O
+activity	O
+in	O
+embryonic	O
+cortico	O
+-	O
+hippocampal	O
+neurosphere	O
+-	O
+derived	O
+progenitors	O
+,	O
+5	O
+days	O
+upon	O
+transduction	O
+,	O
+in	O
+vitro	O
+.	O
+
+In	O
+cultures	O
+transduced	O
+with	O
+Ngn2	O
+retrovirus	O
+,	O
+we	O
+found	O
+that	O
+27	O
+.	O
+2	O
+%	O
+(	O
++	O
+/	O
+-	O
+4	O
+.	O
+1	O
+%	O
+)	O
+of	O
+the	O
+PH3	O
++	O
+cells	O
+had	O
+been	O
+transduced	O
+(	O
+Figure	O
+I1	O
+-	O
+J	O
+)	O
+.	O
+
+These	O
+cells	O
+were	O
+immunopositive	O
+for	O
+MAP2	O
+(	O
+Figure	O
+5I1	O
+and	O
+I2	O
+)	O
+and	O
+therefore	O
+represented	O
+dividing	O
+neuroblasts	O
+.	O
+
+By	O
+contrast	O
+,	O
+in	O
+NeuroD1	O
+transduced	O
+cultures	O
+,	O
+only	O
+7	O
+.	O
+3	O
+%	O
+of	O
+PH3	O
++	O
+cells	O
+were	O
+GFP	O
++	O
+(	O
+Figure	O
+5H1	O
+,	O
+H2	O
+and	O
+J	O
+)	O
+.	O
+
+All	O
+of	O
+the	O
+NeuroD1	O
+-	O
+transduced	O
+cells	O
+became	O
+MAP2	O
++	O
+(	O
+Figure	O
+5H	O
+)	O
+.	O
+
+To	O
+confirm	O
+this	O
+data	O
+we	O
+pulse	O
+-	O
+labeled	O
+transduced	O
+cultures	O
+with	O
+chlorodeoxyuridine	O
+(	O
+CldU	O
+)	O
+for	O
+48	O
+hours	O
+,	O
+five	O
+days	O
+after	O
+differentiation	O
+.	O
+
+In	O
+contrast	O
+to	O
+NeuroD1	O
+-	O
+transduced	O
+cultures	O
+,	O
+we	O
+observed	O
+dividing	O
+cells	O
+transduced	O
+with	O
+Ngn2	O
+retrovirus	O
+that	O
+were	O
+positive	O
+for	O
+PH3	O
+and	O
+that	O
+had	O
+incorporated	O
+CldU	O
+(	O
+Figure	O
+5K	O
+-	O
+L2	O
+)	O
+.	O
+
+As	O
+the	O
+number	O
+of	O
+cells	O
+PH3	O
++	O
+/	O
+CldU	O
++	O
+/	O
+GFP	O
++	O
+we	O
+observed	O
+was	O
+low	O
+,	O
+we	O
+did	O
+not	O
+quantify	O
+this	O
+finding	O
+.	O
+
+Collectively	O
+,	O
+we	O
+have	O
+shown	O
+that	O
+Ngn2	O
+is	O
+required	O
+for	O
+granule	O
+neuroblast	O
+production	O
+and	O
+amplification	O
+and	O
+that	O
+in	O
+the	O
+absence	O
+of	O
+Ngn2	O
+the	O
+progenitors	O
+arrest	O
+in	O
+the	O
+cell	O
+cycle	O
+.	O
+
+NeuroD1	O
+,	O
+on	O
+the	O
+other	O
+hand	O
+,	O
+induces	O
+cell	O
+cycle	O
+exit	O
+and	O
+promotes	O
+rapid	O
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+.	O
+
+NeuroD1	O
+directs	O
+neuronal	O
+differentiation	O
+and	O
+maturation	O
+
+Based	O
+on	O
+our	O
+previous	O
+observations	O
+we	O
+proposed	O
+that	O
+Ngn2	O
+primarily	O
+controls	O
+amplification	O
+of	O
+granule	O
+neuroblasts	O
+and	O
+NeuroD1	O
+directs	O
+neuronal	O
+differentiation	O
+.	O
+
+To	O
+test	O
+this	O
+hypothesis	O
+,	O
+we	O
+overexpressed	O
+Ngn2	O
+or	O
+NeuroD1	O
+in	O
+E14	O
+.	O
+5	O
+cortico	O
+-	O
+hippocampal	O
+neurospheres	O
+and	O
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+effects	O
+after	O
+5	O
+days	O
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+differentiation	O
+of	O
+the	O
+progenitors	O
+.	O
+
+All	O
+cortico	O
+-	O
+hippocampal	O
+progenitors	O
+expressed	O
+Pax6	O
+prior	O
+to	O
+differentiation	O
+(	O
+Figure	O
+S5	O
+)	O
+.	O
+
+After	O
+5	O
+days	O
+,	O
+both	O
+factors	O
+suppressed	O
+Pax6	O
+and	O
+Sox2	O
+(	O
+Figure	O
+S5	O
+,	O
+figure	O
+6C	O
+)	O
+and	O
+induced	O
+expression	O
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+Tbr1	O
+,	O
+Map2	O
+,	O
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+-	O
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+(	O
+Figure	O
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+E	O
+)	O
+.	O
+
+Interestingly	O
+,	O
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+-	O
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+cells	O
+co	O
+-	O
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+NeuroD1	O
+.	O
+
+Based	O
+on	O
+these	O
+findings	O
+,	O
+we	O
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+induces	O
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+,	O
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+.	O
+
+We	O
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+both	O
+transcription	O
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+either	O
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+Thus	O
+,	O
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+E14	O
+.	O
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+three	O
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+/	O
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+,	O
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+eminence	O
+(	O
+LGE	O
+)	O
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+mesencephalon	O
+(	O
+VM	O
+)	O
+.	O
+
+Ngn2	O
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+normally	O
+limited	O
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+,	O
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+it	O
+does	O
+not	O
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+LGE	O
+tissue	O
+[	O
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+In	O
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+,	O
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+,	O
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+,	O
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+]	O
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+In	O
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+,	O
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+-	O
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+,	O
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+(	O
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+)	O
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+
+When	O
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+,	O
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+-	O
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+(	O
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+)	O
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+
+We	O
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+-	O
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+(	O
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+)	O
+.	O
+
+Thus	O
+,	O
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+-	O
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+-	O
+,	O
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+-	O
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+-	O
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+progenitors	O
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+
+Our	O
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+-	O
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+As	O
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+next	O
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+,	O
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+vivo	O
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+them	O
+with	O
+those	O
+of	O
+Ngn2	O
+.	O
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+We	O
+injected	O
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+33	O
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+,	O
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+eGFP	O
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+ventricles	O
+E15	O
+.	O
+5	O
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+,	O
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+7A	O
+)	O
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+
+Three	O
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+,	O
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+analyzed	O
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++	O
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+The	O
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++	O
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+-	O
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++	O
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++	O
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+
+In	O
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++	O
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+The	O
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+-	O
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+-	O
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+)	O
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+In	O
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+,	O
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+-	O
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++	O
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+-	O
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+.	O
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+)	O
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+
+None	O
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+these	O
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+stained	O
+for	O
+GFAP	O
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+Figure	O
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+)	O
+.	O
+
+They	O
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+in	O
+the	O
+external	O
+layers	O
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+both	O
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+and	O
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+blades	O
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+,	O
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+I	O
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+)	O
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+
+When	O
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+Ngn2	O
+-	O
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+-	O
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+few	O
+of	O
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+(	O
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+1	O
++	O
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+-	O
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+Figure	O
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+)	O
+.	O
+
+They	O
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+,	O
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+,	O
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+the	O
+ventral	O
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+dorsal	O
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+
+In	O
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+,	O
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+greater	O
+proportion	O
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+.	O
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++	O
+/	O
+-	O
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+.	O
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+Figure	O
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+)	O
+,	O
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+vast	O
+majority	O
+of	O
+the	O
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+-	O
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+.	O
+
+Immunohistochemistry	O
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+,	O
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+)	O
+.	O
+
+Indeed	O
+,	O
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+proportion	O
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+progenitors	O
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+became	O
+NeuN	O
++	O
+was	O
+no	O
+greater	O
+than	O
+in	O
+rats	B
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+with	O
+the	O
+control	O
+virus	O
+(	O
+Figure	O
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+)	O
+.	O
+
+As	O
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+,	O
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+in	O
+utero	O
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+experiments	O
+confirm	O
+that	O
+NeuroD1	O
+has	O
+a	O
+stronger	O
+neuron	O
+-	O
+inducing	O
+effect	O
+than	O
+Ngn2	O
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+in	O
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+.	O
+
+Involvement	O
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+Mash1	O
+,	O
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+,	O
+Tbr	O
+and	O
+NeuroD	O
+proteins	O
+during	O
+human	B
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+neurogenesis	O
+
+Finally	O
+,	O
+we	O
+examined	O
+whether	O
+the	O
+transcription	O
+factors	O
+and	O
+cellular	O
+markers	O
+that	O
+are	O
+expressed	O
+in	O
+rodents	O
+are	O
+also	O
+expressed	O
+in	O
+human	B
+hippocampus	O
+.	O
+
+We	O
+performed	O
+immunohistochemistry	O
+on	O
+aged	O
+human	B
+hippocampal	O
+DG	O
+and	O
+found	O
+GFAP	O
+-	O
+,	O
+Sox2	O
+-	O
+,	O
+Pax6	O
+-	O
+,	O
+Nestin	O
+-	O
+,	O
+Prox1	O
+-	O
+and	O
+NeuN	O
+-	O
+immunopositive	O
+cells	O
+.	O
+
+This	O
+indicates	O
+that	O
+radial	O
+glia	O
+-	O
+like	O
+stem	O
+cells	O
+,	O
+neural	O
+progenitors	O
+and	O
+mature	O
+granule	O
+neurons	O
+are	O
+present	O
+in	O
+the	O
+aged	O
+human	B
+hippocampus	O
+(	O
+Figure	O
+8A	O
+-	O
+E	O
+)	O
+.	O
+
+While	O
+Prox1	O
+is	O
+found	O
+mainly	O
+in	O
+granule	O
+neurons	O
+,	O
+Sox2	O
+and	O
+Pax6	O
+are	O
+exclusively	O
+localized	O
+to	O
+cells	O
+in	O
+the	O
+SGZ	O
+(	O
+Figure	O
+8D	O
+and	O
+E	O
+)	O
+.	O
+
+As	O
+for	O
+aged	O
+rodents	O
+,	O
+we	O
+did	O
+not	O
+observe	O
+the	O
+presence	O
+of	O
+Mash1	O
+,	O
+Ngn2	O
+,	O
+Tbr2	O
+,	O
+Tbr1	O
+and	O
+NeuroD1	O
+proteins	O
+in	O
+aged	O
+human	B
+hippocampus	O
+,	O
+using	O
+immunohistochemistry	O
+.	O
+
+However	O
+,	O
+we	O
+could	O
+identify	O
+the	O
+presence	O
+of	O
+the	O
+transcripts	O
+,	O
+using	O
+RT	O
+-	O
+PCR	O
+(	O
+Figure	O
+8F	O
+)	O
+.	O
+
+In	O
+addition	O
+,	O
+we	O
+detected	O
+mRNA	O
+for	O
+Prox1	O
+,	O
+Calbindin1	O
+and	O
+Calbindin2	O
+/	O
+Calretinin	O
+(	O
+Figure	O
+8F	O
+)	O
+.	O
+
+Interestingly	O
+,	O
+we	O
+also	O
+observed	O
+Sonic	O
+Hedgehog	O
+and	O
+Wnt	O
+-	O
+3A	O
+transcripts	O
+,	O
+indicating	O
+that	O
+they	O
+are	O
+present	O
+in	O
+the	O
+human	B
+DG	O
+and	O
+supporting	O
+previous	O
+claims	O
+that	O
+they	O
+are	O
+important	O
+for	O
+the	O
+regulation	O
+of	O
+adult	O
+hippocampal	O
+neurogenesis	O
+(	O
+Figure	O
+8F	O
+;	O
+[	O
+34	O
+]	O
+,	O
+[	O
+35	O
+]	O
+)	O
+.	O
+
+Finally	O
+,	O
+we	O
+also	O
+found	O
+mRNA	O
+for	O
+GLAST	O
+,	O
+Pax6	O
+and	O
+GFAP	O
+which	O
+suggests	O
+that	O
+radial	O
+glia	O
+-	O
+like	O
+stem	O
+cells	O
+are	O
+present	O
+in	O
+the	O
+adult	O
+human	B
+hippocampus	O
+,	O
+and	O
+may	O
+play	O
+a	O
+role	O
+in	O
+adult	O
+human	B
+hippocampal	O
+neurogenesis	O
+(	O
+Figure	O
+8F	O
+;	O
+[	O
+8	O
+]	O
+)	O
+.	O
+
+Overall	O
+,	O
+our	O
+data	O
+show	O
+that	O
+different	O
+proteins	O
+known	O
+to	O
+play	O
+key	O
+roles	O
+in	O
+rodent	B
+hippocampal	O
+granule	O
+neurogenesis	O
+are	O
+present	O
+in	O
+the	O
+adult	O
+human	B
+hippocampus	O
+.	O
+
+Discussion	O
+
+In	O
+this	O
+study	O
+we	O
+determine	O
+the	O
+functions	O
+of	O
+Ngn2	O
+and	O
+NeuroD1	O
+during	O
+hippocampal	O
+neurogenesis	O
+.	O
+
+First	O
+,	O
+we	O
+map	O
+the	O
+hierarchy	O
+of	O
+molecular	O
+markers	O
+of	O
+neurogenesis	O
+in	O
+the	O
+DG	O
+.	O
+
+Second	O
+,	O
+we	O
+describe	O
+that	O
+Ngn2	O
+is	O
+necessary	O
+for	O
+granule	O
+progenitor	O
+production	O
+/	O
+amplification	O
+.	O
+
+Third	O
+,	O
+we	O
+demonstrate	O
+that	O
+NeuroD1	O
+directs	O
+neuronal	O
+differentiation	O
+of	O
+granule	O
+progenitors	O
+.	O
+
+Finally	O
+,	O
+we	O
+show	O
+that	O
+different	O
+cellular	O
+markers	O
+expressed	O
+during	O
+hippocampal	O
+neurogenesis	O
+in	O
+rodents	O
+are	O
+present	O
+in	O
+human	B
+.	O
+
+Sequential	O
+expression	O
+of	O
+different	O
+transcription	O
+factors	O
+and	O
+cellular	O
+markers	O
+during	O
+hippocampal	O
+neurogenesis	O
+
+We	O
+clarified	O
+the	O
+pattern	O
+of	O
+expression	O
+of	O
+various	O
+markers	O
+expressed	O
+during	O
+postnatal	O
+and	O
+adult	O
+hippocampal	O
+granule	O
+neurogenesis	O
+in	O
+detail	O
+.	O
+
+We	O
+found	O
+that	O
+the	O
+transcription	O
+factor	O
+Pax6	O
+is	O
+initially	O
+expressed	O
+by	O
+both	O
+radial	O
+glia	O
+stem	O
+cells	O
+(	O
+type	O
+-	O
+1	O
+)	O
+and	O
+early	O
+amplifying	O
+progenitors	O
+(	O
+type	O
+-	O
+2a	O
+)	O
+.	O
+
+The	O
+next	O
+transcription	O
+factor	O
+to	O
+appear	O
+in	O
+chronology	O
+is	O
+Mash1	O
+.	O
+
+Mash1	O
+expression	O
+characterizes	O
+the	O
+early	O
+stage	O
+of	O
+hippocampal	O
+progenitor	O
+amplification	O
+(	O
+early	O
+type	O
+-	O
+2a	O
+)	O
+.	O
+
+The	O
+role	O
+of	O
+Mash1	O
+during	O
+hippocampal	O
+granule	O
+neurogenesis	O
+is	O
+still	O
+unclear	O
+.	O
+
+Mash1	O
+null	O
+mutant	O
+mice	B
+do	O
+not	O
+display	O
+any	O
+clear	O
+malformation	O
+of	O
+the	O
+DG	O
+[	O
+20	O
+]	O
+.	O
+
+However	O
+,	O
+overexpression	O
+of	O
+Mash1	O
+alone	O
+in	O
+the	O
+DG	O
+leads	O
+to	O
+the	O
+generation	O
+of	O
+oligodendrocytes	O
+[	O
+36	O
+]	O
+.	O
+
+Based	O
+on	O
+these	O
+observations	O
+,	O
+we	O
+hypothesize	O
+that	O
+Mash1	O
+-	O
+expressing	O
+cells	O
+are	O
+not	O
+yet	O
+committed	O
+towards	O
+a	O
+granule	O
+cell	O
+fate	O
+.	O
+
+They	O
+may	O
+still	O
+have	O
+the	O
+potential	O
+to	O
+generate	O
+both	O
+neurons	O
+and	O
+oligodendrocytes	O
+,	O
+as	O
+is	O
+the	O
+case	O
+in	O
+the	O
+SVZ	O
+[	O
+37	O
+]	O
+.	O
+
+In	O
+agreement	O
+with	O
+different	O
+developing	O
+brain	O
+regions	O
+,	O
+we	O
+found	O
+that	O
+Ngn2	O
+starts	O
+to	O
+be	O
+expressed	O
+in	O
+Mash1	O
+-	O
+positive	O
+transiently	O
+amplifying	O
+progenitors	O
+,	O
+i	O
+.	O
+e	O
+.	O
+"	O
+late	O
+type	O
+-	O
+2a	O
+cells	O
+"	O
+according	O
+to	O
+the	O
+classification	O
+we	O
+propose	O
+.	O
+
+We	O
+observed	O
+that	O
+Pax6	O
+expression	O
+persisted	O
+longer	O
+than	O
+that	O
+of	O
+Mash1	O
+,	O
+in	O
+Ngn2	O
+-	O
+expressing	O
+cells	O
+(	O
+late	O
+type	O
+-	O
+2a	O
+cells	O
+)	O
+,	O
+in	O
+juvenile	O
+but	O
+not	O
+adult	O
+DG	O
+(	O
+Fig	O
+.	O
+1	O
+and	O
+figure	O
+S1	O
+)	O
+.	O
+
+Later	O
+on	O
+,	O
+Ngn2	O
+is	O
+downregulated	O
+,	O
+whilst	O
+Tbr2	O
+expression	O
+persists	O
+(	O
+type	O
+-	O
+2b	O
+cells	O
+)	O
+.	O
+
+The	O
+transition	O
+from	O
+amplifying	O
+progenitor	O
+to	O
+neuroblast	O
+is	O
+defined	O
+by	O
+the	O
+expression	O
+of	O
+NeuroD1	O
+.	O
+
+Thus	O
+,	O
+Ngn2	O
+is	O
+expressed	O
+at	O
+the	O
+beginning	O
+of	O
+the	O
+transiently	O
+amplifying	O
+progenitor	O
+phase	O
+while	O
+NeuroD1	O
+marks	O
+the	O
+end	O
+of	O
+that	O
+period	O
+.	O
+
+This	O
+applies	O
+both	O
+to	O
+the	O
+juvenile	O
+and	O
+adult	O
+rat	B
+brain	O
+[	O
+21	O
+]	O
+,	O
+[	O
+25	O
+]	O
+.	O
+
+After	O
+NeuroD1	O
+is	O
+turned	O
+on	O
+the	O
+progenitors	O
+leave	O
+the	O
+cell	O
+cycle	O
+,	O
+gradually	O
+mature	O
+,	O
+express	O
+PSA	O
+-	O
+NCAM	O
+,	O
+NeuroD2	O
+,	O
+Calretinin	O
+,	O
+Prox1	O
+,	O
+Tbr1	O
+and	O
+,	O
+finally	O
+,	O
+NeuN	O
+.	O
+
+NeuroD1	O
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+persists	O
+at	O
+low	O
+levels	O
+in	O
+mature	O
+neurons	O
+(	O
+Figure	O
+9	O
+;	O
+[	O
+10	O
+]	O
+)	O
+.	O
+
+We	O
+found	O
+the	O
+sequential	O
+expression	O
+of	O
+these	O
+markers	O
+conserved	O
+in	O
+juvenile	O
+(	O
+P2	O
+and	O
+2	O
+weeks	O
+)	O
+and	O
+adult	O
+rodent	B
+brains	O
+.	O
+
+Importantly	O
+,	O
+we	O
+observed	O
+that	O
+the	O
+same	O
+transcription	O
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+and	O
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+markers	O
+are	O
+also	O
+present	O
+in	O
+the	O
+adult	O
+human	B
+hippocampus	O
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+spatially	O
+in	O
+a	O
+manner	O
+reminiscent	O
+with	O
+what	O
+we	O
+saw	O
+in	O
+rodents	O
+.	O
+
+It	O
+is	O
+possible	O
+,	O
+however	O
+,	O
+that	O
+some	O
+of	O
+these	O
+markers	O
+are	O
+expressed	O
+for	O
+longer	O
+or	O
+shorter	O
+periods	O
+at	O
+postnatal	O
+and	O
+adult	O
+stages	O
+of	O
+hippocampal	O
+progenitor	O
+maturation	O
+.	O
+
+Moreover	O
+,	O
+one	O
+can	O
+ask	O
+to	O
+which	O
+extent	O
+the	O
+number	O
+of	O
+divisions	O
+occurring	O
+during	O
+neuroblasts	O
+maturation	O
+is	O
+conserved	O
+at	O
+postnatal	O
+and	O
+adult	O
+stages	O
+of	O
+neurogenesis	O
+.	O
+
+A	O
+new	O
+function	O
+for	O
+Ngn2	O
+in	O
+maintenance	O
+of	O
+a	O
+progenitor	O
+state	O
+for	O
+granule	O
+neuron	O
+production	O
+/	O
+amplification	O
+during	O
+embryonic	O
+and	O
+postnatal	O
+hippocampal	O
+neurogenesis	O
+
+In	O
+agreement	O
+with	O
+earlier	O
+work	O
+,	O
+we	O
+confirm	O
+that	O
+Ngn2	O
+is	O
+indispensable	O
+for	O
+hippocampal	O
+development	O
+and	O
+plays	O
+a	O
+vital	O
+role	O
+in	O
+postnatal	O
+hippocampal	O
+granule	O
+neurogenesis	O
+.	O
+
+Ngn2	O
+null	O
+mutant	O
+animals	O
+display	O
+a	O
+reduced	O
+size	O
+of	O
+the	O
+cornu	O
+ammonis	O
+and	O
+a	O
+malformed	O
+DG	O
+(	O
+Figure	O
+3	O
+and	O
+4	O
+;	O
+[	O
+20	O
+]	O
+)	O
+.	O
+
+We	O
+show	O
+that	O
+the	O
+number	O
+of	O
+newborn	O
+neurons	O
+(	O
+incorporated	O
+BrdU	O
+)	O
+is	O
+decreased	O
+in	O
+absence	O
+of	O
+Ngn2	O
+,	O
+but	O
+hippocampal	O
+granule	O
+neuron	O
+subtype	O
+specification	O
+is	O
+not	O
+affected	O
+,	O
+post	O
+-	O
+nataly	O
+.	O
+
+Likewise	O
+,	O
+neurons	O
+from	O
+other	O
+brain	O
+regions	O
+,	O
+e	O
+.	O
+g	O
+.	O
+ventral	O
+midbrain	O
+dopamine	O
+neurons	O
+,	O
+can	O
+be	O
+generated	O
+in	O
+the	O
+absence	O
+of	O
+Ngn2	O
+[	O
+30	O
+]	O
+,	O
+[	O
+31	O
+]	O
+.	O
+
+The	O
+reduced	O
+numbers	O
+of	O
+mature	O
+neurons	O
+in	O
+the	O
+hippocampus	O
+and	O
+ventral	O
+midbrain	O
+of	O
+Ngn2	O
+null	O
+mutant	O
+animals	O
+does	O
+not	O
+appear	O
+to	O
+be	O
+due	O
+to	O
+cell	O
+death	O
+or	O
+migration	O
+defects	O
+[	O
+20	O
+]	O
+,	O
+[	O
+31	O
+]	O
+.	O
+
+Instead	O
+it	O
+may	O
+be	O
+due	O
+to	O
+a	O
+defect	O
+in	O
+the	O
+generation	O
+and	O
+/	O
+or	O
+amplification	O
+of	O
+neuronal	O
+progenitors	O
+.	O
+
+Indeed	O
+,	O
+in	O
+the	O
+hippocampus	O
+of	O
+postnatal	O
+animals	O
+,	O
+we	O
+observed	O
+that	O
+cells	O
+lacking	O
+Ngn2	O
+arrest	O
+in	O
+the	O
+cell	O
+cycle	O
+,	O
+maintain	O
+Pax6	O
+expression	O
+and	O
+cease	O
+to	O
+proliferate	O
+.	O
+
+When	O
+overexpressed	O
+in	O
+neural	O
+progenitors	O
+in	O
+vitro	O
+,	O
+Ngn2	O
+lead	O
+to	O
+up	O
+-	O
+regulation	O
+of	O
+NeuroD1	O
+and	O
+caused	O
+neuronal	O
+differentiation	O
+(	O
+Figure	O
+6	O
+)	O
+,	O
+which	O
+was	O
+not	O
+always	O
+the	O
+case	O
+when	O
+we	O
+overexpressed	O
+the	O
+same	O
+factor	O
+in	O
+vivo	O
+(	O
+Figure	O
+7L	O
+,	O
+N	O
+and	O
+O	O
+)	O
+.	O
+
+We	O
+also	O
+saw	O
+that	O
+Ngn2	O
+does	O
+not	O
+always	O
+efficiently	O
+induce	O
+cell	O
+cycle	O
+exit	O
+.	O
+
+Typically	O
+some	O
+mitotically	O
+active	O
+eGFP	O
++	O
+cells	O
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+present	O
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+rats	B
+injected	O
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+Ngn2	O
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+(	O
+Figure	O
+7P	O
+)	O
+,	O
+and	O
+we	O
+observed	O
+that	O
+cultured	O
+Ngn2	O
+-	O
+transduced	O
+cells	O
+are	O
+still	O
+capable	O
+of	O
+dividing	O
+.	O
+
+Thus	O
+,	O
+Ngn2	O
+does	O
+not	O
+always	O
+promote	O
+cell	O
+cycle	O
+exit	O
+and	O
+neuronal	O
+commitment	O
+,	O
+but	O
+depending	O
+on	O
+the	O
+state	O
+of	O
+the	O
+cells	O
+,	O
+Ngn2	O
+may	O
+instead	O
+promote	O
+alternate	O
+cellular	O
+fates	O
+[	O
+38	O
+]	O
+-	O
+[	O
+40	O
+]	O
+.	O
+
+Indeed	O
+,	O
+an	O
+earlier	O
+study	O
+has	O
+shown	O
+that	O
+Ngn2	O
+-	O
+overexpressing	O
+progenitors	O
+generate	O
+oligodendrocytes	O
+when	O
+grafted	O
+to	O
+the	O
+adult	O
+spinal	O
+cord	O
+[	O
+40	O
+]	O
+.	O
+
+We	O
+have	O
+also	O
+seen	O
+that	O
+Ngn2	O
+-	O
+overexpressing	O
+neural	O
+progenitors	O
+from	O
+the	O
+embryonic	O
+midbrain	O
+form	O
+astrocytes	O
+when	O
+grafted	O
+to	O
+the	O
+striatum	O
+(	O
+unpublished	O
+observations	O
+)	O
+.	O
+
+Probably	O
+,	O
+Ngn2	O
+cannot	O
+influence	O
+already	O
+committed	O
+cells	O
+,	O
+but	O
+rather	O
+would	O
+control	O
+neuroblasts	O
+production	O
+.	O
+
+One	O
+could	O
+speculate	O
+that	O
+Ngn2	O
+oscillates	O
+during	O
+granule	O
+neuron	O
+formation	O
+,	O
+as	O
+recently	O
+demonstrated	O
+during	O
+neocorticogenesis	O
+[	O
+41	O
+]	O
+,	O
+[	O
+42	O
+]	O
+.	O
+
+NeuroD1	O
+,	O
+but	O
+not	O
+Ngn2	O
+,	O
+is	O
+obligatory	O
+for	O
+granule	O
+neuron	O
+progenitor	O
+differentiation	O
+
+Hippocampal	O
+granule	O
+progenitors	O
+can	O
+mature	O
+and	O
+express	O
+Tbr1	O
+and	O
+Prox1	O
+,	O
+both	O
+during	O
+the	O
+development	O
+and	O
+postnatally	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+Ngn2	O
+.	O
+
+Because	O
+neuronal	O
+differentiation	O
+still	O
+occurs	O
+in	O
+Ngn2	O
+null	O
+mice	B
+,	O
+it	O
+is	O
+clear	O
+that	O
+compensatory	O
+,	O
+Ngn2	O
+-	O
+independent	O
+mechanisms	O
+induce	O
+NeuroD1	O
+expression	O
+.	O
+
+One	O
+candidate	O
+is	O
+Ngn1	O
+,	O
+which	O
+is	O
+expressed	O
+during	O
+neocorticogenesis	O
+,	O
+the	O
+specification	O
+of	O
+olfactory	O
+sensory	O
+neurons	O
+and	O
+during	O
+embryonic	O
+rat	B
+hippocampal	O
+development	O
+[	O
+43	O
+]	O
+-	O
+[	O
+47	O
+]	O
+.	O
+
+Both	O
+Ngn1	O
+and	O
+Ngn2	O
+regulate	O
+NeuroD1	O
+[	O
+19	O
+]	O
+,	O
+[	O
+48	O
+]	O
+.	O
+
+The	O
+introduction	O
+of	O
+two	O
+mutant	O
+forms	O
+of	O
+Ngn1	O
+,	O
+a	O
+deletion	O
+of	O
+the	O
+basic	O
+region	O
+of	O
+Ngn1	O
+and	O
+a	O
+substitution	O
+of	O
+two	O
+amino	O
+acids	O
+in	O
+the	O
+C	O
+-	O
+terminal	O
+basic	O
+region	O
+,	O
+prevents	O
+NeuroD1	O
+expression	O
+and	O
+neuronal	O
+differentiation	O
+[	O
+48	O
+]	O
+.	O
+
+The	O
+double	O
+null	O
+Ngn1	O
+/	O
+Ngn2	O
+mutant	O
+displays	O
+a	O
+more	O
+severe	O
+phenotype	O
+than	O
+single	O
+gene	O
+(	O
+Ngn1	O
+or	O
+Ngn2	O
+)	O
+mutant	O
+mice	B
+.	O
+
+For	O
+example	O
+,	O
+the	O
+total	O
+brain	O
+size	O
+of	O
+the	O
+double	O
+mutants	O
+is	O
+much	O
+smaller	O
+[	O
+10	O
+]	O
+,	O
+[	O
+32	O
+]	O
+.	O
+
+If	O
+the	O
+role	O
+of	O
+Ngn1	O
+during	O
+hippocampal	O
+neurogenesis	O
+is	O
+to	O
+activate	O
+NeuroD1	O
+and	O
+that	O
+of	O
+Ngn2	O
+is	O
+to	O
+control	O
+granule	O
+neuroblasts	O
+production	O
+/	O
+amplification	O
+,	O
+the	O
+DG	O
+of	O
+double	O
+Ngn1	O
+/	O
+Ngn2	O
+knockout	O
+mice	B
+should	O
+resemble	O
+that	O
+of	O
+NeuroD1	O
+null	O
+mutant	O
+mice	B
+.	O
+
+We	O
+demonstrated	O
+that	O
+NeuroD1	O
+directs	O
+neuronal	O
+differentiation	O
+both	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+.	O
+
+In	O
+progenitors	O
+isolated	O
+from	O
+different	O
+embryonic	O
+brain	O
+regions	O
+and	O
+cultured	O
+in	O
+vitro	O
+,	O
+we	O
+found	O
+that	O
+overexpression	O
+of	O
+NeuroD1	O
+induced	O
+neuronal	O
+differentiation	O
+.	O
+
+The	O
+neurons	O
+generated	O
+expressed	O
+PSA	O
+-	O
+NCAM	O
+,	O
+Dcx	O
+and	O
+MAP2	O
+.	O
+
+After	O
+in	O
+utero	O
+retroviral	O
+vector	O
+-	O
+mediated	O
+gene	O
+delivery	O
+,	O
+virtually	O
+all	O
+cells	O
+transduced	O
+with	O
+NeuroD1	O
+became	O
+neurons	O
+.	O
+
+In	O
+contrast	O
+,	O
+progenitors	O
+transduced	O
+with	O
+Ngn2	O
+or	O
+control	O
+retroviruses	O
+adopted	O
+a	O
+neuron	O
+-	O
+like	O
+morphology	O
+in	O
+only	O
+70	O
+-	O
+85	O
+%	O
+of	O
+cases	O
+.	O
+
+Under	O
+in	O
+vitro	O
+cell	O
+culture	O
+conditions	O
+,	O
+when	O
+we	O
+overexpressed	O
+Ngn2	O
+in	O
+progenitors	O
+derived	O
+from	O
+the	O
+LGE	O
+we	O
+observed	O
+robust	O
+expression	O
+of	O
+NeuroD1	O
+and	O
+neuronal	O
+differentiation	O
+.	O
+
+These	O
+in	O
+vitro	O
+results	O
+differ	O
+from	O
+those	O
+we	O
+obtained	O
+when	O
+we	O
+transduced	O
+the	O
+embryonic	O
+brain	O
+with	O
+a	O
+viral	O
+vector	O
+expressing	O
+Ngn2	O
+.	O
+
+In	O
+this	O
+latter	O
+case	O
+,	O
+Ngn2	O
+did	O
+not	O
+induce	O
+neurons	O
+and	O
+the	O
+transduced	O
+cells	O
+did	O
+not	O
+express	O
+NeuroD1	O
+.	O
+
+Therefore	O
+,	O
+Ngn2	O
+appears	O
+to	O
+direct	O
+non	O
+-	O
+neuronal	O
+cell	O
+type	O
+specification	O
+in	O
+vivo	O
+[	O
+38	O
+]	O
+-	O
+[	O
+40	O
+]	O
+.	O
+
+Taken	O
+together	O
+,	O
+we	O
+have	O
+confirmed	O
+that	O
+NeuroD1	O
+plays	O
+a	O
+key	O
+role	O
+in	O
+neuronal	O
+differentiation	O
+in	O
+the	O
+hippocampus	O
+,	O
+both	O
+during	O
+development	O
+and	O
+in	O
+the	O
+adult	O
+brain	O
+.	O
+
+Concluding	O
+remark	O
+
+We	O
+present	O
+a	O
+detailed	O
+classification	O
+of	O
+different	O
+stages	O
+in	O
+hippocampal	O
+neurogenesis	O
+.	O
+
+Our	O
+detailed	O
+molecular	O
+mapping	O
+of	O
+hippocampal	O
+neurogenesis	O
+allows	O
+for	O
+a	O
+more	O
+accurate	O
+analysis	O
+of	O
+how	O
+new	O
+factors	O
+stimulate	O
+neurogenesis	O
+at	O
+different	O
+steps	O
+in	O
+the	O
+development	O
+of	O
+granule	O
+neurons	O
+.	O
+
+Thereby	O
+we	O
+hope	O
+to	O
+facilitate	O
+the	O
+development	O
+of	O
+new	O
+agents	O
+,	O
+which	O
+stimulate	O
+endogenous	O
+progenitors	O
+in	O
+the	O
+treatment	O
+of	O
+diseases	O
+.	O
+
+Materials	O
+and	O
+Methods	O
+
+Animal	O
+tissue	O
+preparation	O
+
+The	O
+creation	O
+of	O
+the	O
+Ngn2	O
+transgenic	O
+mice	B
+was	O
+reported	O
+elsewhere	O
+(	O
+ref	O
+guillemot	O
+)	O
+.	O
+
+Heterozygote	O
+male	O
+and	O
+female	O
+mice	B
+were	O
+crossed	O
+to	O
+obtain	O
+WT	O
+,	O
+heterozygote	O
+(	O
+Ngn2	O
++	O
+/	O
+GFP	O
+)	O
+and	O
+null	O
+mutant	O
+(	O
+Ngn2GFP	O
+/	O
+GFP	O
+)	O
+animals	O
+.	O
+
+Tails	O
+of	O
+the	O
+Ngn2	O
+offspring	O
+were	O
+used	O
+to	O
+obtain	O
+DNA	O
+for	O
+determination	O
+of	O
+the	O
+genotype	O
+using	O
+a	O
+polymerase	O
+chain	O
+reaction	O
+(	O
+PCR	O
+)	O
+assay	O
+as	O
+previously	O
+reported	O
+[	O
+31	O
+]	O
+.	O
+
+As	O
+null	O
+mutant	O
+Ngn2GFP	O
+/	O
+GFP	O
+do	O
+not	O
+survive	O
+longer	O
+than	O
+2	O
+.	O
+5	O
+-	O
+3	O
+weeks	O
+after	O
+birth	O
+,	O
+Ngn2GFP	O
+/	O
+GFP	O
+and	O
+their	O
+littermates	O
+were	O
+sacrificed	O
+at	O
+the	O
+postnatal	O
+ages	O
+of	O
+two	O
+days	O
+(	O
+P2	O
+)	O
+or	O
+two	O
+weeks	O
+for	O
+this	O
+study	O
+.	O
+
+Neurogenesis	O
+was	O
+assessed	O
+in	O
+two	O
+weeks	O
+or	O
+two	O
+months	O
+old	O
+WT	O
+mice	B
+.	O
+
+Sprague	O
+Dawley	O
+pregnant	O
+rats	B
+were	O
+ordered	O
+from	O
+B	O
+&	O
+K	O
+Universal	O
+Ltd	O
+,	O
+Sollentuna	O
+,	O
+Sweden	O
+(	O
+hppt	O
+:	O
+/	O
+/	O
+www	O
+.	O
+bku	O
+.	O
+com	O
+)	O
+.	O
+
+All	O
+animals	O
+were	O
+housed	O
+in	O
+groups	O
+with	O
+ad	O
+libitum	O
+access	O
+to	O
+food	O
+and	O
+water	O
+at	O
+a	O
+12	O
+-	O
+h	O
+light	O
+/	O
+dark	O
+cycle	O
+.	O
+
+All	O
+experimental	O
+procedures	O
+conducted	O
+in	O
+this	O
+study	O
+had	O
+been	O
+approved	O
+by	O
+the	O
+Ethical	O
+Committee	O
+at	O
+Lund	O
+University	O
+.	O
+
+For	O
+immunohistochemical	O
+analysis	O
+,	O
+mice	B
+(	O
+from	O
+two	O
+weeks	O
+old	O
+and	O
+adult	O
+stage	O
+)	O
+and	O
+juvenile	O
+rats	B
+were	O
+sacrificed	O
+by	O
+transcardial	O
+perfusion	O
+with	O
+saline	O
+for	O
+5	O
+-	O
+10	O
+minutes	O
+,	O
+followed	O
+by	O
+4	O
+%	O
+paraformaldehyde	O
+(	O
+PFA	O
+)	O
+for	O
+10	O
+minutes	O
+.	O
+
+Brains	O
+were	O
+kept	O
+in	O
+PFA	O
+overnight	O
+at	O
+4	O
+degrees	O
+C	O
+and	O
+subsequently	O
+cryopreserved	O
+in	O
+a	O
+20	O
+-	O
+30	O
+%	O
+sucrose	O
+/	O
+0	O
+.	O
+1	O
+M	O
+phosphate	O
+buffer	O
+solution	O
+until	O
+sectioning	O
+on	O
+a	O
+microtome	O
+apparatus	O
+(	O
+30	O
+micro	O
+m	O
+thickness	O
+sections	O
+,	O
+Microm	O
+Zeiss	O
+)	O
+.	O
+
+Seven	O
+series	O
+of	O
+coronal	O
+sections	O
+were	O
+cut	O
+throughout	O
+the	O
+brain	O
+.	O
+
+Free	O
+-	O
+floating	O
+sections	O
+were	O
+preserved	O
+in	O
+antifreeze	O
+solution	O
+until	O
+immunohistochemistry	O
+was	O
+performed	O
+.	O
+
+Heads	O
+of	O
+postanatal	O
+two	O
+days	O
+old	O
+mice	B
+were	O
+decapitated	O
+and	O
+soaked	O
+in	O
+PFA	O
+4	O
+%	O
+for	O
+24	O
+hours	O
+,	O
+at	O
+4	O
+degrees	O
+C	O
+and	O
+transferred	O
+into	O
+sucrose	O
+solution	O
+until	O
+sectioning	O
+on	O
+cryostat	O
+apparatus	O
+(	O
+16	O
+micro	O
+m	O
+thickness	O
+;	O
+Leica	O
+CM3000	O
+)	O
+.	O
+
+Sections	O
+were	O
+mounted	O
+on	O
+Superfrost	O
+glass	O
+slides	O
+and	O
+stored	O
+at	O
+-	O
+80	O
+degrees	O
+C	O
+until	O
+immunohistochemistry	O
+was	O
+performed	O
+.	O
+
+Cloning	O
+,	O
+subcloning	O
+,	O
+virus	O
+production	O
+and	O
+titer	O
+measurement	O
+
+The	O
+Moloney	O
+leukemia	O
+-	O
+derived	O
+retroviral	O
+vectors	O
+used	O
+in	O
+this	O
+study	O
+,	O
+pCMMP	O
+-	O
+IRES2eGFP	O
+-	O
+WPRE	O
+and	O
+pCMMP	O
+-	O
+Ngn2	O
+-	O
+IRES2eGFP	O
+-	O
+WPRE	O
+were	O
+previously	O
+described	O
+[	O
+40	O
+]	O
+,	O
+[	O
+49	O
+]	O
+.	O
+
+To	O
+generate	O
+the	O
+construct	O
+pCMMP	O
+-	O
+NeuroD1	O
+-	O
+IRES2eGFP	O
+-	O
+WPRE	O
+,	O
+mouse	B
+NeuroD1	O
+cDNA	O
+was	O
+amplified	O
+from	O
+a	O
+pCS2	O
++	O
+mtNeuroD1	O
+plasmid	O
+(	O
+kindly	O
+provided	O
+by	O
+Professor	O
+Jackie	O
+Lee	O
+,	O
+Denver	O
+university	O
+,	O
+Boulder	O
+,	O
+USA	O
+)	O
+by	O
+PCR	O
+to	O
+introduce	O
+the	O
+restriction	O
+sites	O
+PmeI	O
+in	O
+5	O
+'	O
+and	O
+XhoI	O
+in	O
+3	O
+'	O
+.	O
+
+Amplification	O
+of	O
+cDNA	O
+was	O
+performed	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+The	O
+construction	O
+was	O
+verified	O
+by	O
+enzymatic	O
+restriction	O
+and	O
+by	O
+DNA	O
+sequencing	O
+using	O
+BigDye	O
+3	O
+.	O
+1	O
+(	O
+ABI	O
+)	O
+.	O
+
+All	O
+infectious	O
+particles	O
+were	O
+produced	O
+using	O
+the	O
+producer	O
+cell	O
+line	O
+293VSV	O
+-	O
+G	O
+and	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+The	O
+titer	O
+of	O
+each	O
+retrovirus	O
+was	O
+measured	O
+by	O
+flow	O
+-	O
+cytometry	O
+based	O
+on	O
+eGFP	O
+expression	O
+,	O
+four	O
+days	O
+following	O
+infection	O
+of	O
+HT1080	O
+cells	O
+and	O
+ranged	O
+from	O
+0	O
+.	O
+5	O
+x	O
+109	O
+-	O
+2	O
+.	O
+1	O
+x	O
+109	O
+TU	O
+/	O
+ml	O
+(	O
+All	O
+details	O
+on	O
+how	O
+to	O
+produce	O
+infectious	O
+particles	O
+can	O
+be	O
+provided	O
+upon	O
+request	O
+)	O
+.	O
+
+Neurosphere	O
+generation	O
+,	O
+transduction	O
+and	O
+differentiation	O
+
+Pregnant	O
+female	O
+Sprague	B
+-	I
+Dawley	I
+rats	I
+(	O
+B	O
+&	O
+K	O
+Universal	O
+,	O
+Sollentuna	O
+,	O
+Sweden	O
+)	O
+were	O
+terminally	O
+anesthetized	O
+by	O
+an	O
+overdose	O
+of	O
+sodium	O
+pentobarbital	O
+(	O
+i	O
+.	O
+p	O
+.	O
+,	O
+60	O
+ng	O
+/	O
+ml	O
+)	O
+.	O
+
+Embryos	O
+at	O
+stage	O
+embryonic	O
+day	O
+E14	O
+.	O
+5	O
+(	O
+Plug	O
+day	O
+as	O
+day	O
+0	O
+)	O
+were	O
+collected	O
+and	O
+cortical	O
+-	O
+hippocampal	O
+neurospheres	O
+were	O
+generated	O
+following	O
+dissection	O
+of	O
+the	O
+dorso	O
+-	O
+posterior	O
+part	O
+of	O
+the	O
+cortical	O
+tissue	O
+,	O
+and	O
+generated	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+second	O
+passage	O
+(	O
+P2	O
+)	O
+neurospheres	O
+were	O
+used	O
+to	O
+study	O
+the	O
+effect	O
+of	O
+the	O
+overexpression	O
+of	O
+Ngn2	O
+and	O
+NeuroD1	O
+on	O
+neuronal	O
+differentiation	O
+.	O
+
+Each	O
+well	O
+,	O
+containing	O
+an	O
+equal	O
+starting	O
+population	O
+of	O
+200	O
+,	O
+000	O
+cells	O
+/	O
+ml	O
+,	O
+corresponding	O
+to	O
+15	O
+-	O
+25	O
+neurospheres	O
+,	O
+was	O
+transduced	O
+independently	O
+with	O
+each	O
+retrovirus	O
+at	O
+a	O
+multiplicity	O
+of	O
+infection	O
+(	O
+MOI	O
+)	O
+of	O
+1	O
+,	O
+in	O
+proliferation	O
+medium	O
+supplemented	O
+by	O
+protamine	O
+-	O
+sulfate	O
+(	O
+4	O
+mg	O
+/	O
+ml	O
+,	O
+Sigma	O
+)	O
+.	O
+
+To	O
+induce	O
+differentiation	O
+,	O
+the	O
+medium	O
+was	O
+replaced	O
+with	O
+normal	O
+basic	O
+differentiation	O
+medium	O
+two	O
+days	O
+post	O
+-	O
+transduction	O
+and	O
+subsequently	O
+changed	O
+every	O
+other	O
+day	O
+until	O
+fixation	O
+.	O
+
+Immunocytochemistry	O
+,	O
+immunohistochemistry	O
+and	O
+microscopy	O
+
+The	O
+antibodies	O
+used	O
+in	O
+this	O
+study	O
+are	O
+:	O
+rabbit	B
+anti	O
+-	O
+GFAP	O
+(	O
+1	O
+:	O
+1000	O
+;	O
+DAKO	O
+)	O
+,	O
+mouse	B
+anti	O
+-	O
+Nestin	O
+(	O
+1	O
+:	O
+100	O
+;	O
+BD	O
+PharMingen	O
+)	O
+,	O
+guinea	B
+pig	I
+anti	O
+-	O
+Glast	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Chemicon	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Prox1	O
+(	O
+1	O
+:	O
+1000	O
+;	O
+Covance	O
+)	O
+,	O
+goat	B
+anti	O
+-	O
+Ngn2	O
+(	O
+1	O
+:	O
+20	O
+;	O
+Santa	O
+Cruz	O
+)	O
+,	O
+goat	B
+anti	O
+-	O
+NeuroD1	O
+(	O
+1	O
+:	O
+200	O
+;	O
+Santa	O
+Cruz	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Pax6	O
+(	O
+1	O
+:	O
+150	O
+;	O
+Covance	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Trb2	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Chemicon	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Trb1	O
+:	O
+(	O
+1	O
+:	O
+1000	O
+;	O
+Chemicon	O
+)	O
+,	O
+goat	B
+anti	O
+-	O
+Dcx	O
+:	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Santa	O
+Cruz	O
+)	O
+,	O
+mouse	B
+anti	O
+-	O
+PSA	O
+-	O
+NCAM	O
+:	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Chemicon	O
+)	O
+,	O
+mouse	B
+anti	O
+-	O
+NeuN	O
+(	O
+1	O
+:	O
+300	O
+;	O
+Chemicon	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Calretinin	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Swant	O
+)	O
+;	O
+mouse	B
+anti	O
+-	O
+Sox2	O
+(	O
+1	O
+:	O
+100	O
+;	O
+R	O
+&	O
+D	O
+systems	O
+)	O
+,	O
+mouse	B
+anti	O
+-	O
+Mash1	O
+(	O
+1	O
+:	O
+100	O
+;	O
+BD	O
+PharMingen	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+NeuroD2	O
+(	O
+1	O
+:	O
+300	O
+;	O
+ABCAM	O
+)	O
+,	O
+mouse	B
+anti	O
+-	O
+MAP2	O
+(	O
+1	O
+:	O
+500	O
+;	O
+Sigma	O
+)	O
+,	O
+rabbit	B
+anti	O
+-	O
+Ki67	O
+(	O
+1	O
+:	O
+150	O
+;	O
+NovaCastra	O
+)	O
+and	O
+rabbit	B
+anti	O
+-	O
+phospho	O
+-	O
+Histone	O
+H3	O
+.	O
+
+The	O
+secondary	O
+antibodies	O
+(	O
+1	O
+:	O
+200	O
+)	O
+Cy2	O
+,	O
+FITC	O
+,	O
+Cy3	O
+and	O
+Cy5	O
+were	O
+from	O
+Jackson	O
+IR	O
+laboratories	O
+,	O
+Alexa	O
+-	O
+fluor	O
+488	O
+,	O
+568	O
+,	O
+595	O
+and	O
+647	O
+from	O
+Invitrogen	O
+-	O
+Molecular	O
+Probes	O
+.	O
+
+DAPI	O
+(	O
+1	O
+:	O
+1000	O
+)	O
+was	O
+purchased	O
+from	O
+Sigma	O
+.	O
+
+For	O
+immunocytochemistry	O
+,	O
+cultures	O
+were	O
+fixed	O
+in	O
+4	O
+%	O
+paraformaldehyde	O
+at	O
+day	O
+five	O
+,	O
+rinsed	O
+with	O
+PBS	O
+three	O
+times	O
+prior	O
+to	O
+pre	O
+-	O
+incubation	O
+with	O
+a	O
+blocking	O
+solution	O
+(	O
+10	O
+%	O
+donkey	B
+serum	O
+,	O
+0	O
+.	O
+25	O
+%	O
+TritonX100	O
+in	O
+PBS	O
+)	O
+for	O
+1	O
+hour	O
+.	O
+
+The	O
+remainder	O
+of	O
+the	O
+procedure	O
+was	O
+performed	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+Specimen	O
+analyses	O
+were	O
+performed	O
+using	O
+a	O
+Leica	O
+confocal	O
+microscope	O
+(	O
+Leica	O
+software	O
+,	O
+equipped	O
+with	O
+a	O
+GreNe	O
+and	O
+a	O
+HeNe	O
+laser	O
+,	O
+using	O
+the	O
+following	O
+lines	O
+of	O
+excitation	O
+:	O
+488	O
+nm	O
+,	O
+594	O
+nm	O
+and	O
+647	O
+nm	O
+)	O
+.	O
+
+Samples	O
+were	O
+analyzed	O
+using	O
+20	O
+x	O
+,	O
+40	O
+x	O
+and	O
+63	O
+x	O
+objectives	O
+,	O
+sometimes	O
+zoomed	O
+.	O
+
+Figures	O
+were	O
+composed	O
+in	O
+CANVAS	O
+-	O
+X	O
+software	O
+.	O
+
+Bromo	O
+-	O
+deoxyuridine	O
+(	O
+BrdU	O
+)	O
+and	O
+Cloro	O
+-	O
+deoxyuridine	O
+(	O
+CldU	O
+)	O
+pulse	O
+labeling	O
+and	O
+immunohisto	O
+-	O
+and	O
+immunocyto	O
+-	O
+chemistry	O
+
+To	O
+assess	O
+cell	O
+proliferation	O
+and	O
+ongoing	O
+neurogenesis	O
+in	O
+vivo	O
+,	O
+animals	O
+were	O
+injected	O
+with	O
+BrdU	O
+(	O
+100	O
+mg	O
+/	O
+kg	O
+,	O
+Sigma	O
+)	O
+,	O
+two	O
+hours	O
+prior	O
+to	O
+sacrifice	O
+(	O
+for	O
+both	O
+P2	O
+and	O
+two	O
+weeks	O
+old	O
+Ngn2	O
+mice	B
+)	O
+.	O
+
+To	O
+assess	O
+neurogenesis	O
+,	O
+BrdU	O
+(	O
+100	O
+mg	O
+/	O
+kg	O
+)	O
+was	O
+injected	O
+48	O
+hours	O
+prior	O
+to	O
+sacrifice	O
+(	O
+for	O
+P2	O
+animals	O
+,	O
+BrdU	O
+was	O
+injected	O
+in	O
+pregnant	O
+dams	O
+half	O
+day	O
+prior	O
+to	O
+give	O
+birth	O
+)	O
+.	O
+
+Immunohistochemistry	O
+was	O
+carried	O
+on	O
+as	O
+described	O
+above	O
+using	O
+a	O
+rat	B
+anti	O
+-	O
+CldU	O
+/	O
+BrdU	O
+primary	O
+antibody	O
+(	O
+1	O
+:	O
+200	O
+,	O
+monoclonal	O
+,	O
+Immunologicalsdirect	O
+,	O
+Oxfordshire	O
+,	O
+UK	O
+)	O
+,	O
+with	O
+an	O
+additional	O
+denaturation	O
+in	O
+1	O
+M	O
+HCl	O
+for	O
+30	O
+minutes	O
+prior	O
+to	O
+pre	O
+-	O
+incubation	O
+with	O
+serum	O
+.	O
+
+To	O
+assess	O
+the	O
+neuronal	O
+-	O
+inducing	O
+activity	O
+of	O
+Ngn2	O
+and	O
+NeuroD1	O
+,	O
+transduced	O
+cultures	O
+were	O
+incubated	O
+with	O
+CldU	O
+(	O
+20	O
+micro	O
+M	O
+,	O
+Sigma	O
+)	O
+for	O
+2	O
+days	O
+,	O
+after	O
+a	O
+period	O
+of	O
+differentiation	O
+of	O
+five	O
+days	O
+.	O
+
+For	O
+immunocytochemistry	O
+,	O
+cultures	O
+were	O
+fixed	O
+with	O
+4	O
+%	O
+paraformaldehyde	O
+at	O
+day	O
+7	O
+,	O
+rinsed	O
+with	O
+PBS	O
+three	O
+times	O
+,	O
+treated	O
+with	O
+1	O
+M	O
+HCl	O
+at	O
+65	O
+degrees	O
+C	O
+for	O
+5	O
+-	O
+10	O
+min	O
+,	O
+pre	O
+-	O
+incubated	O
+and	O
+then	O
+incubated	O
+with	O
+a	O
+rat	B
+anti	O
+-	O
+CldU	O
+/	O
+BrdU	O
+antibody	O
+and	O
+other	O
+primary	O
+antibodies	O
+.	O
+
+The	O
+remainder	O
+of	O
+the	O
+procedure	O
+was	O
+performed	O
+according	O
+to	O
+the	O
+protocol	O
+for	O
+immunohistochemistry	O
+already	O
+mentioned	O
+.	O
+
+In	O
+utero	O
+surgery	O
+
+Timed	O
+pregnant	O
+female	O
+Sprague	B
+Dawley	I
+rats	I
+with	O
+embryos	O
+at	O
+gestational	O
+age	O
+E15	O
+.	O
+5	O
+were	O
+anesthetized	O
+with	O
+halothane	O
+.	O
+
+The	O
+mother	O
+was	O
+placed	O
+in	O
+the	O
+lower	O
+level	O
+of	O
+a	O
+two	O
+-	O
+level	O
+wooden	O
+stage	O
+.	O
+
+The	O
+abdomen	O
+was	O
+shaved	O
+with	O
+an	O
+electric	O
+razor	O
+and	O
+then	O
+cleaned	O
+with	O
+70	O
+%	O
+alcohol	O
+.	O
+
+A	O
+2	O
+-	O
+3	O
+cm	O
+midline	O
+laparotomy	O
+was	O
+performed	O
+.	O
+
+Each	O
+uterine	O
+horn	O
+was	O
+carefully	O
+taken	O
+out	O
+individually	O
+and	O
+the	O
+number	O
+of	O
+embryos	O
+recorded	O
+.	O
+
+One	O
+horn	O
+was	O
+then	O
+placed	O
+back	O
+inside	O
+the	O
+mother	O
+,	O
+whilst	O
+the	O
+other	O
+horn	O
+was	O
+prepared	O
+for	O
+injection	O
+.	O
+
+The	O
+embryos	O
+were	O
+kept	O
+moist	O
+with	O
+constant	O
+application	O
+of	O
+warm	O
+saline	O
+to	O
+prevent	O
+dehydration	O
+.	O
+
+Approximately	O
+2	O
+micro	O
+l	O
+of	O
+viral	O
+suspension	O
+(	O
+1	O
+x	O
+10	O
+^	O
+9TU	O
+/	O
+ml	O
+)	O
+was	O
+injected	O
+into	O
+the	O
+lateral	O
+ventricle	O
+of	O
+each	O
+embryo	O
+,	O
+except	O
+for	O
+the	O
+embryo	O
+closest	O
+to	O
+the	O
+vagina	O
+.	O
+
+After	O
+the	O
+injections	O
+,	O
+the	O
+uterine	O
+horns	O
+were	O
+placed	O
+back	O
+into	O
+the	O
+abdomen	O
+.	O
+
+The	O
+abdominal	O
+wall	O
+and	O
+the	O
+overlying	O
+skin	O
+were	O
+then	O
+sutured	O
+.	O
+
+Care	O
+was	O
+taken	O
+not	O
+to	O
+damage	O
+abdominal	O
+muscles	O
+so	O
+that	O
+normal	O
+delivery	O
+of	O
+the	O
+pups	O
+was	O
+possible	O
+at	O
+term	O
+.	O
+
+The	O
+entire	O
+surgery	O
+generally	O
+took	O
+about	O
+45	O
+minutes	O
+to	O
+one	O
+hour	O
+.	O
+
+Each	O
+mother	O
+was	O
+allowed	O
+to	O
+recover	O
+in	O
+her	O
+cage	O
+before	O
+being	O
+returned	O
+to	O
+the	O
+animal	O
+stable	O
+.	O
+
+Shredded	O
+paper	O
+was	O
+added	O
+to	O
+each	O
+cage	O
+to	O
+encourage	O
+nesting	O
+and	O
+special	O
+care	O
+was	O
+taken	O
+not	O
+to	O
+stress	O
+the	O
+mothers	O
+.	O
+
+Following	O
+normal	O
+delivery	O
+,	O
+the	O
+pups	O
+were	O
+allowed	O
+to	O
+develop	O
+to	O
+adulthood	O
+up	O
+to	O
+two	O
+weeks	O
+.	O
+
+Quantification	O
+
+For	O
+the	O
+in	O
+vivo	O
+experiment	O
+,	O
+manual	O
+cell	O
+counting	O
+was	O
+performed	O
+on	O
+18	O
+and	O
+30	O
+micro	O
+m	O
+thick	O
+brain	O
+sections	O
+for	O
+two	O
+days	O
+and	O
+two	O
+weeks	O
+old	O
+animals	O
+,	O
+respectively	O
+.	O
+
+The	O
+brain	O
+of	O
+P2	O
+animals	O
+was	O
+cut	O
+into	O
+10	O
+series	O
+of	O
+coronal	O
+sections	O
+;	O
+the	O
+brain	O
+of	O
+two	O
+-	O
+weeks	O
+old	O
+animals	O
+was	O
+cut	O
+into	O
+7	O
+-	O
+8	O
+series	O
+of	O
+coronal	O
+sections	O
+.	O
+
+For	O
+each	O
+staining	O
+,	O
+one	O
+-	O
+two	O
+series	O
+from	O
+three	O
+to	O
+five	O
+different	O
+individuals	O
+were	O
+analyzed	O
+per	O
+genotype	O
+using	O
+a	O
+confocal	O
+microscope	O
+with	O
+1	O
+,	O
+2	O
+or	O
+3	O
+lines	O
+of	O
+excitation	O
+,	O
+in	O
+sequential	O
+scanning	O
+in	O
+order	O
+to	O
+avoid	O
+false	O
+positives	O
+.	O
+
+When	O
+two	O
+series	O
+were	O
+analyzed	O
+,	O
+only	O
+one	O
+series	O
+was	O
+counted	O
+.	O
+
+The	O
+mean	O
+number	O
+of	O
+cells	O
+per	O
+hippocampus	O
+expressing	O
+the	O
+markers	O
+of	O
+interest	O
+,	O
+was	O
+calculated	O
+for	O
+each	O
+brain	O
+,	O
+based	O
+on	O
+the	O
+analysis	O
+of	O
+6	O
+-	O
+8	O
+consecutive	O
+dorsal	O
+hippocampal	O
+sections	O
+.	O
+
+The	O
+final	O
+mean	O
+number	O
+of	O
+cells	O
+per	O
+section	O
+was	O
+calculated	O
+by	O
+adding	O
+the	O
+mean	O
+number	O
+from	O
+each	O
+individual	O
+.	O
+
+We	O
+expressed	O
+the	O
+data	O
+as	O
+the	O
+mean	O
+number	O
+of	O
+positive	O
+cells	O
++	O
+/	O
+-	O
+standard	O
+error	O
+of	O
+the	O
+mean	O
+(	O
+SEM	O
+)	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+more	O
+than	O
+25	O
+Ngn2	O
+null	O
+,	O
+>	O
+45	O
+Ngn2	O
+heterozygotes	O
+,	O
+and	O
+>	O
+60	O
+WT	O
+individuals	O
+(	O
+including	O
+rats	B
+injected	O
+with	O
+retroviruses	O
+)	O
+were	O
+analyzed	O
+,	O
+in	O
+total	O
+.	O
+
+Statistical	O
+comparison	O
+was	O
+performed	O
+using	O
+one	O
+-	O
+factor	O
+analysis	O
+of	O
+variance	O
+(	O
+ANOVA	O
+)	O
+with	O
+transcription	O
+factor	O
+,	O
+cellular	O
+marker	O
+,	O
+genotype	O
+or	O
+time	O
+as	O
+variables	O
+,	O
+followed	O
+by	O
+post	O
+-	O
+hoc	O
+analysis	O
+when	O
+significant	O
+differences	O
+were	O
+observed	O
+,	O
+using	O
+Statview	O
+5	O
+.	O
+0	O
+software	O
+(	O
+SAS	O
+institute	O
+Inc	O
+.	O
+)	O
+.	O
+
+For	O
+cell	O
+culture	O
+experiments	O
+,	O
+three	O
+independent	O
+experiments	O
+were	O
+performed	O
+,	O
+each	O
+in	O
+duplicate	O
+.	O
+
+The	O
+counting	O
+was	O
+based	O
+on	O
+seven	O
+randomly	O
+chosen	O
+different	O
+fields	O
+of	O
+view	O
+.	O
+
+For	O
+each	O
+diagram	O
+,	O
+the	O
+level	O
+of	O
+significance	O
+(	O
+p	O
+-	O
+value	O
+)	O
+is	O
+represented	O
+as	O
+follows	O
+:	O
+P	O
+<	O
+0	O
+.	O
+05	O
+=	O
+*	O
+;	O
+P	O
+<	O
+0	O
+.	O
+001	O
+=	O
+*	O
+*	O
+;	O
+P	O
+<	O
+0	O
+.	O
+0001	O
+=	O
+*	O
+*	O
+*	O
+.	O
+
+All	O
+data	O
+are	O
+expressed	O
+as	O
++	O
+/	O
+-	O
+standard	O
+error	O
+of	O
+the	O
+mean	O
+(	O
+SEM	O
+)	O
+.	O
+
+Human	B
+sample	O
+and	O
+RT	O
+-	O
+PCR	O
+
+The	O
+brain	O
+from	O
+a	O
+64	O
+year	O
+-	O
+old	O
+male	O
+was	O
+provided	O
+by	O
+the	O
+Harvard	O
+Brain	O
+Tissue	O
+Resource	O
+Center	O
+.	O
+
+The	O
+individual	O
+whose	O
+brain	O
+tissue	O
+was	O
+being	O
+analyzed	O
+gave	O
+written	O
+consent	O
+for	O
+storage	O
+and	O
+use	O
+of	O
+his	O
+tissue	O
+for	O
+research	O
+.	O
+
+Five	O
+millimeters	O
+thick	O
+fresh	O
+human	B
+hippocampal	O
+tissue	O
+sample	O
+was	O
+snap	O
+frozen	O
+.	O
+
+The	O
+frozen	O
+tissue	O
+block	O
+was	O
+cut	O
+into	O
+20	O
+series	O
+of	O
+coronal	O
+sections	O
+,	O
+using	O
+a	O
+cryostat	O
+.	O
+
+Every	O
+10	O
+sections	O
+,	O
+one	O
+section	O
+was	O
+placed	O
+in	O
+an	O
+Eppendorf	O
+tube	O
+,	O
+on	O
+dry	O
+ice	O
+.	O
+
+Pooled	O
+sections	O
+were	O
+used	O
+for	O
+RT	O
+-	O
+PCR	O
+.	O
+
+Total	O
+RNA	O
+was	O
+prepared	O
+using	O
+Trizol	O
+and	O
+RNAeasy	O
+,	O
+supplemented	O
+with	O
+RNAGuard	O
+as	O
+previously	O
+described	O
+[	O
+49	O
+]	O
+.	O
+
+The	O
+RNA	O
+was	O
+digested	O
+with	O
+shrimp	O
+DNAse	O
+before	O
+cDNA	O
+synthesis	O
+,	O
+which	O
+was	O
+performed	O
+using	O
+a	O
+mix	O
+of	O
+oligo	O
+-	O
+dT	O
+and	O
+random	O
+hexamer	O
+primers	O
+and	O
+SuperscriptII	O
+reverse	O
+transcriptase	O
+.	O
+
+Advantage2	O
+polymerase	O
+mix	O
+(	O
+Clontech	O
+/	O
+BRL	O
+)	O
+was	O
+used	O
+for	O
+PCR	O
+,	O
+with	O
+the	O
+following	O
+cycling	O
+conditions	O
+:	O
+10	O
+cycles	O
+of	O
+94	O
+degrees	O
+C	O
+for	O
+30	O
+seconds	O
+,	O
+68	O
+degrees	O
+C	O
+for	O
+2	O
+minutes	O
+,	O
+30	O
+cycles	O
+of	O
+94	O
+degrees	O
+C	O
+for	O
+30	O
+seconds	O
+,	O
+60	O
+degrees	O
+C	O
+for	O
+1	O
+minute	O
+,	O
+68	O
+degrees	O
+C	O
+for	O
+1	O
+minute	O
+and	O
+30	O
+seconds	O
+,	O
+one	O
+cycle	O
+of	O
+68	O
+degrees	O
+C	O
+for	O
+2	O
+minutes	O
+,	O
+soak	O
+at	O
+16	O
+degrees	O
+C	O
+.	O
+
+Primers	O
+marked	O
+*	O
+were	O
+designed	O
+by	O
+PrimerBank	O
+.	O
+
+hRPS18	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GCCTTTGCCATCACTGCCAT	O
+and	O
+hRPS18	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+GCCAGTGGTCTTGGTGTGCT	O
+,	O
+hPAX6	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GCCCTGGAGAAAGAGTTTGA	O
+hPAX6	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+GGGGAAATGAGTCCTGTTGA	O
+,	O
+hTBR1	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GCGGACACCAATGTGCAAGG	O
+and	O
+hTBR1	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CGAGGGGGTCAGGCGGTCCA	O
+,	O
+hTBR2	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GACCTGTGGCAAAGCCGACA	O
+and	O
+hTBR2	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+GGGGGTGTCTCTATCCAAGA	O
+,	O
+hPDHX	O
+(	O
+=	O
+PROX1	O
+)	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GGGACACTACGGTTCCGTTT	O
+and	O
+hPDHX	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CTCTCCATCCCAGCTTACAT	O
+,	O
+hNGN2	O
+(	O
+sense	O
+)	O
+*	O
+5	O
+'	O
+-	O
+CATCAAGAAGACCCGTAGAC	O
+and	O
+hNGN2	O
+(	O
+antisense	O
+)	O
+*	O
+5	O
+'	O
+-	O
+CAACACTGCCTCGGAGAAG	O
+,	O
+hMASH1	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+CCTGGATCCGCATGGAAAGC	O
+and	O
+hMASH1	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CCTGGATCCCCCCTCAGAAC	O
+,	O
+hNEUROD1	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GCTCAGGACCTACTAACAAC	O
+and	O
+hNEUROD1	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CAAAGCGTCTGAACGAAGGA	O
+,	O
+hGLAST	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+CATCAGGGAAGATGGGAATG	O
+and	O
+hGLAST	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CCACGGGGGCATACCACATT	O
+,	O
+hNEST	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+CAGGAGCGGCTGCGGGCTAC	O
+and	O
+hNEST	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CAGGGCTGAGGGGTGGTGCC	O
+,	O
+hGFAP	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+CCACGAGGAGGAGGTTCGGG	O
+and	O
+hGFAP	O
+(	O
+antisense	O
+)	O
+5	O
+-	O
+GGAATGGTGATCCGGTTCTC	O
+,	O
+hCALB2	O
+(	O
+=	O
+Calretinin	O
+)	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GGCTCTGGCATGATGTCAAA	O
+and	O
+hCALB2	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+GGGCATCCAGCTCATGCTCG	O
+,	O
+hCALB1	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GCGAAAGAAGGCTGGATTGG	O
+and	O
+hCALB1	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CCCTCCATCCGACAAAGCCA	O
+,	O
+hSOX2	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+GGAGAACCCCAAGATGCACA	O
+and	O
+hSOX2	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+GAGGAAGAGGTAACCACAGG	O
+,	O
+hWNT3A	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+CCGAGGGCATCAAGATTGGC	O
+and	O
+hWNT3A	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+TCGGGTTGCGACCACCAGCA	O
+,	O
+hSHH	O
+*	O
+(	O
+sense	O
+)	O
+5	O
+'	O
+-	O
+ACTCCGAGCGATTTAAGGAA	O
+and	O
+hSHH	O
+*	O
+(	O
+antisense	O
+)	O
+5	O
+'	O
+-	O
+CAGACGTGGTGATGTCCACT	O
+.	O
+
+Supporting	O
+Information	O
+
+A	O
+novel	O
+DNA	O
+-	O
+binding	O
+protein	O
+modulating	O
+methicillin	O
+resistance	O
+in	O
+Staphylococcus	B
+aureus	I
+
+Abstract	O
+
+Background	O
+
+Methicillin	O
+resistance	O
+in	O
+Staphylococcus	B
+aureus	I
+is	O
+conferred	O
+by	O
+the	O
+mecA	O
+-	O
+encoded	O
+penicillin	O
+-	O
+binding	O
+protein	O
+PBP2a	O
+.	O
+
+Additional	O
+genomic	O
+factors	O
+are	O
+also	O
+known	O
+to	O
+influence	O
+resistance	O
+levels	O
+in	O
+strain	O
+specific	O
+ways	O
+,	O
+although	O
+little	O
+is	O
+known	O
+about	O
+their	O
+contribution	O
+to	O
+resistance	O
+phenotypes	O
+in	O
+clinical	O
+isolates	O
+.	O
+
+Here	O
+we	O
+searched	O
+for	O
+novel	O
+proteins	O
+binding	O
+to	O
+the	O
+mec	O
+operator	O
+,	O
+in	O
+an	O
+attempt	O
+to	O
+identify	O
+new	O
+factor	O
+(	O
+s	O
+)	O
+controlling	O
+methicillin	O
+resistance	O
+phenotypes	O
+.	O
+
+Results	O
+
+Analysis	O
+of	O
+proteins	O
+binding	O
+to	O
+a	O
+DNA	O
+fragment	O
+containing	O
+the	O
+mec	O
+operator	O
+region	O
+identified	O
+a	O
+novel	O
+,	O
+putative	O
+helix	O
+-	O
+turn	O
+-	O
+helix	O
+DNA	O
+-	O
+binding	O
+protein	O
+,	O
+SA1665	O
+.	O
+
+Nonpolar	O
+deletion	O
+of	O
+SA1665	O
+,	O
+in	O
+heterogeneously	O
+methicillin	O
+resistant	O
+S	B
+.	I
+aureus	I
+(	O
+MRSA	B
+)	O
+of	O
+different	O
+genetic	O
+backgrounds	O
+,	O
+increased	O
+methicillin	O
+resistance	O
+levels	O
+in	O
+a	O
+strain	O
+dependent	O
+manner	O
+.	O
+
+This	O
+phenotype	O
+could	O
+be	O
+fully	O
+complemented	O
+by	O
+reintroducing	O
+SA1665	O
+in	O
+trans	O
+.	O
+
+Northern	O
+and	O
+Western	O
+blot	O
+analyses	O
+,	O
+however	O
+,	O
+revealed	O
+that	O
+SA1665	O
+had	O
+no	O
+visible	O
+influence	O
+on	O
+mecA	O
+transcription	O
+or	O
+amounts	O
+of	O
+PBP2a	O
+produced	O
+.	O
+
+Conclusion	O
+
+SA1665	O
+is	O
+a	O
+new	O
+chromosomal	O
+factor	O
+which	O
+influences	O
+methicillin	O
+resistance	O
+in	O
+MRSA	B
+.	O
+
+Although	O
+SA1665	O
+bound	O
+to	O
+the	O
+mecA	O
+promoter	O
+region	O
+,	O
+it	O
+had	O
+no	O
+apparent	O
+influence	O
+on	O
+mecA	O
+transcription	O
+or	O
+translation	O
+,	O
+suggesting	O
+that	O
+this	O
+predicted	O
+DNA	O
+-	O
+binding	O
+protein	O
+modulates	O
+resistance	O
+indirectly	O
+,	O
+most	O
+likely	O
+through	O
+the	O
+control	O
+of	O
+other	O
+genomic	O
+factors	O
+which	O
+contribute	O
+to	O
+resistance	O
+.	O
+
+Background	O
+
+Methicillin	O
+resistant	O
+S	B
+.	I
+aureus	I
+(	O
+MRSA	B
+)	O
+are	O
+an	O
+ever	O
+increasing	O
+threat	O
+,	O
+both	O
+in	O
+clinical	O
+settings	O
+and	O
+more	O
+recently	O
+as	O
+an	O
+emerging	O
+community	O
+acquired	O
+pathogen	O
+.	O
+
+Their	O
+invasiveness	O
+and	O
+pathogenesis	O
+relies	O
+on	O
+a	O
+variable	O
+arsenal	O
+of	O
+virulence	O
+factors	O
+,	O
+paired	O
+with	O
+resistance	O
+to	O
+virtually	O
+all	O
+beta	O
+-	O
+lactams	O
+and	O
+their	O
+derivatives	O
+.	O
+
+Their	O
+ability	O
+to	O
+rapidly	O
+generate	O
+resistance	O
+to	O
+other	O
+unrelated	O
+classes	O
+of	O
+antibiotics	O
+,	O
+or	O
+to	O
+take	O
+up	O
+additional	O
+resistance	O
+determinants	O
+,	O
+severely	O
+hampers	O
+therapy	O
+and	O
+eradication	O
+.	O
+
+In	O
+S	B
+.	I
+aureus	I
+,	O
+methicillin	O
+resistance	O
+is	O
+conferred	O
+by	O
+an	O
+acquired	O
+,	O
+beta	O
+-	O
+lactam	O
+-	O
+insensitive	O
+penicillin	O
+-	O
+binding	O
+protein	O
+(	O
+PBP	O
+)	O
+,	O
+PBP2a	O
+[	O
+1	O
+-	O
+4	O
+]	O
+.	O
+
+PBP2a	O
+is	O
+encoded	O
+by	O
+mecA	O
+,	O
+which	O
+is	O
+divergently	O
+transcribed	O
+from	O
+its	O
+cognate	O
+regulators	O
+,	O
+mecR1	O
+(	O
+sensor	O
+/	O
+signal	O
+transducer	O
+)	O
+and	O
+mecI	O
+(	O
+repressor	O
+)	O
+.	O
+
+If	O
+mecR1	O
+-	O
+mecI	O
+are	O
+absent	O
+or	O
+truncated	O
+,	O
+transcriptional	O
+control	O
+of	O
+mecA	O
+is	O
+taken	O
+over	O
+by	O
+the	O
+structurally	O
+similar	O
+blaZ	O
+(	O
+penicillinase	O
+)	O
+regulatory	O
+elements	O
+blaR1	O
+/	O
+blaI	O
+,	O
+if	O
+present	O
+.	O
+
+In	O
+the	O
+absence	O
+of	O
+both	O
+regulatory	O
+loci	O
+,	O
+mecA	O
+is	O
+constitutively	O
+transcribed	O
+[	O
+5	O
+,	O
+6	O
+]	O
+.	O
+
+In	O
+the	O
+presence	O
+of	O
+beta	O
+-	O
+lactams	O
+,	O
+the	O
+transmembrane	O
+sensor	O
+/	O
+signal	O
+transducers	O
+BlaR1	O
+/	O
+MecR1	O
+,	O
+undergo	O
+a	O
+conformational	O
+change	O
+,	O
+followed	O
+by	O
+autoproteolytic	O
+cleavage	O
+of	O
+the	O
+n	O
+-	O
+terminal	O
+cytoplasmic	O
+domain	O
+,	O
+leading	O
+to	O
+the	O
+activation	O
+of	O
+the	O
+cytoplasmic	O
+peptidase	O
+and	O
+subsequent	O
+dissociation	O
+of	O
+the	O
+repressor	O
+due	O
+to	O
+proteolytic	O
+degradation	O
+[	O
+7	O
+-	O
+9	O
+]	O
+.	O
+
+However	O
+,	O
+the	O
+signal	O
+transduction	O
+cascade	O
+of	O
+this	O
+regulatory	O
+system	O
+has	O
+still	O
+not	O
+been	O
+completely	O
+elucidated	O
+.	O
+
+Oxacillin	O
+resistance	O
+levels	O
+conferred	O
+by	O
+mecA	O
+are	O
+strain	O
+specific	O
+and	O
+can	O
+vary	O
+greatly	O
+,	O
+with	O
+oxacillin	O
+minimal	O
+inhibitory	O
+concentrations	O
+(	O
+MICs	O
+)	O
+of	O
+different	O
+strains	O
+ranging	O
+from	O
+phenotypically	O
+susceptible	O
+levels	O
+,	O
+as	O
+low	O
+as	O
+1	O
+mu	O
+g	O
+/	O
+ml	O
+up	O
+to	O
+extremely	O
+high	O
+values	O
+of	O
+>	O
+500	O
+mu	O
+g	O
+/	O
+ml	O
+.	O
+
+Methicillin	O
+resistance	O
+is	O
+also	O
+generally	O
+expressed	O
+heterogeneously	O
+.	O
+
+Heterogeneously	O
+resistant	O
+MRSA	B
+,	O
+when	O
+exposed	O
+to	O
+beta	O
+-	O
+lactam	O
+antibiotics	O
+,	O
+segregate	O
+highly	O
+resistant	O
+subpopulations	O
+,	O
+which	O
+are	O
+much	O
+more	O
+resistant	O
+than	O
+the	O
+majority	O
+of	O
+the	O
+cells	O
+[	O
+10	O
+]	O
+.	O
+
+The	O
+frequency	O
+of	O
+highly	O
+resistant	O
+subclones	O
+generated	O
+is	O
+often	O
+well	O
+above	O
+the	O
+spontaneous	O
+mutation	O
+frequency	O
+,	O
+and	O
+once	O
+selected	O
+high	O
+level	O
+resistance	O
+often	O
+remains	O
+stable	O
+,	O
+even	O
+in	O
+the	O
+absence	O
+of	O
+selective	O
+pressure	O
+.	O
+
+There	O
+is	O
+currently	O
+no	O
+satisfactory	O
+genetic	O
+model	O
+which	O
+explains	O
+how	O
+these	O
+higher	O
+resistance	O
+levels	O
+are	O
+triggered	O
+or	O
+selected	O
+and	O
+exactly	O
+what	O
+factors	O
+are	O
+functionally	O
+responsible	O
+for	O
+the	O
+increased	O
+resistance	O
+in	O
+clinical	O
+isolates	O
+.	O
+
+Methicillin	O
+resistance	O
+levels	O
+are	O
+known	O
+to	O
+not	O
+directly	O
+correlate	O
+with	O
+mecA	O
+transcription	O
+or	O
+levels	O
+of	O
+PBP2a	O
+produced	O
+[	O
+11	O
+,	O
+12	O
+]	O
+.	O
+
+However	O
+,	O
+resistance	O
+levels	O
+can	O
+be	O
+manipulated	O
+by	O
+environmental	O
+conditions	O
+,	O
+such	O
+as	O
+temperature	O
+,	O
+pH	O
+,	O
+osmolarity	O
+,	O
+and	O
+medium	O
+composition	O
+[	O
+13	O
+,	O
+14	O
+]	O
+.	O
+
+It	O
+has	O
+been	O
+shown	O
+experimentally	O
+,	O
+that	O
+in	O
+addition	O
+to	O
+mecA	O
+,	O
+methicillin	O
+resistance	O
+depends	O
+on	O
+the	O
+correct	O
+interplay	O
+of	O
+a	O
+multitude	O
+of	O
+genomic	O
+factors	O
+,	O
+termed	O
+fem	O
+/	O
+aux	O
+factors	O
+,	O
+including	O
+genes	O
+involved	O
+in	O
+peptidoglycan	O
+precursor	O
+formation	O
+,	O
+composition	O
+and	O
+turnover	O
+;	O
+teichoic	O
+acid	O
+synthesis	O
+;	O
+and	O
+genes	O
+of	O
+unknown	O
+or	O
+poorly	O
+characterised	O
+functions	O
+[	O
+15	O
+-	O
+18	O
+]	O
+.	O
+
+In	O
+addition	O
+to	O
+structural	O
+genes	O
+,	O
+many	O
+regulatory	O
+loci	O
+have	O
+also	O
+been	O
+shown	O
+to	O
+influence	O
+resistance	O
+levels	O
+,	O
+including	O
+global	O
+regulators	O
+of	O
+virulence	O
+factor	O
+production	O
+such	O
+as	O
+the	O
+quorum	O
+sensing	O
+agr	O
+system	O
+,	O
+the	O
+staphylococcal	O
+accessory	O
+regulator	O
+SarA	O
+and	O
+the	O
+alternate	O
+sigma	O
+factor	O
+sigma	O
+B	O
+[	O
+19	O
+,	O
+20	O
+]	O
+;	O
+regulators	O
+of	O
+metabolism	O
+,	O
+such	O
+as	O
+the	O
+catabolite	O
+control	O
+protein	O
+A	O
+(	O
+CcpA	O
+)	O
+[	O
+21	O
+]	O
+;	O
+and	O
+the	O
+VraSR	O
+two	O
+-	O
+component	O
+sensor	O
+transducer	O
+,	O
+which	O
+induces	O
+the	O
+cell	O
+wall	O
+stress	O
+stimulon	O
+in	O
+response	O
+to	O
+cell	O
+wall	O
+active	O
+antibiotic	O
+challenge	O
+[	O
+22	O
+]	O
+.	O
+
+The	O
+vast	O
+MIC	O
+differences	O
+between	O
+MRSA	B
+strains	O
+,	O
+the	O
+population	O
+heterogeneity	O
+within	O
+single	O
+strains	O
+and	O
+the	O
+dependence	O
+of	O
+resistance	O
+levels	O
+on	O
+external	O
+factors	O
+are	O
+reflected	O
+in	O
+these	O
+many	O
+structural	O
+genes	O
+and	O
+global	O
+regulators	O
+,	O
+which	O
+can	O
+influence	O
+resistance	O
+levels	O
+.	O
+
+While	O
+typically	O
+considered	O
+nosocomial	O
+pathogens	O
+,	O
+new	O
+faster	O
+growing	O
+and	O
+apparently	O
+more	O
+virulent	O
+MRSA	B
+have	O
+begun	O
+spreading	O
+in	O
+the	O
+community	O
+.	O
+
+Interestingly	O
+,	O
+these	O
+emerging	O
+strains	O
+often	O
+express	O
+very	O
+low	O
+methicillin	O
+resistance	O
+,	O
+e	O
+.	O
+g	O
+.	O
+the	O
+MRSA	B
+clone	O
+spreading	O
+amongst	O
+intravenous	O
+drug	O
+users	O
+in	O
+the	O
+Zurich	O
+area	O
+,	O
+which	O
+has	O
+an	O
+in	O
+vitro	O
+doubling	O
+time	O
+of	O
+25	O
+min	O
+,	O
+but	O
+oxacillin	O
+MICs	O
+of	O
+only	O
+0	O
+.	O
+5	O
+to	O
+4	O
+mu	O
+g	O
+/	O
+ml	O
+[	O
+23	O
+]	O
+.	O
+
+This	O
+particular	O
+clone	O
+'	O
+s	O
+low	O
+-	O
+level	O
+resistance	O
+is	O
+partially	O
+due	O
+to	O
+a	O
+promoter	O
+mutation	O
+,	O
+leading	O
+to	O
+tight	O
+repression	O
+of	O
+mecA	O
+,	O
+but	O
+resistance	O
+levels	O
+appear	O
+to	O
+be	O
+mainly	O
+restricted	O
+by	O
+unknown	O
+factors	O
+within	O
+its	O
+genomic	O
+background	O
+[	O
+12	O
+]	O
+.	O
+
+To	O
+identify	O
+potential	O
+factors	O
+involved	O
+in	O
+mecA	O
+regulation	O
+or	O
+methicillin	O
+resistance	O
+levels	O
+in	O
+such	O
+an	O
+extremely	O
+low	O
+level	O
+resistant	O
+MRSA	B
+,	O
+we	O
+performed	O
+DNA	O
+-	O
+binding	O
+protein	O
+purification	O
+assays	O
+,	O
+using	O
+the	O
+mecA	O
+operator	O
+region	O
+as	O
+bait	O
+.	O
+
+A	O
+novel	O
+,	O
+uncharacterized	O
+protein	O
+,	O
+SA1665	O
+,	O
+was	O
+found	O
+to	O
+bind	O
+to	O
+this	O
+DNA	O
+fragment	O
+,	O
+and	O
+shown	O
+to	O
+increase	O
+methicillin	O
+resistance	O
+levels	O
+when	O
+deleted	O
+.	O
+
+Results	O
+
+Identification	O
+of	O
+SA1665	O
+
+MRSA	B
+strain	O
+CHE482	O
+is	O
+the	O
+type	O
+strain	O
+for	O
+the	O
+so	O
+-	O
+called	O
+"	O
+drug	O
+clone	O
+"	O
+spreading	O
+amongst	O
+intravenous	O
+drug	O
+users	O
+in	O
+the	O
+Zurich	O
+area	O
+[	O
+12	O
+,	O
+23	O
+]	O
+.	O
+
+This	O
+strain	O
+carries	O
+mecA	O
+and	O
+expresses	O
+PBP2a	O
+,	O
+but	O
+appears	O
+phenotypically	O
+methicillin	O
+susceptible	O
+by	O
+conventional	O
+phenotypic	O
+tests	O
+.	O
+
+However	O
+,	O
+like	O
+most	O
+other	O
+low	O
+-	O
+level	O
+resistant	O
+MRSA	B
+,	O
+it	O
+can	O
+segregate	O
+a	O
+small	O
+proportion	O
+of	O
+higher	O
+resistant	O
+subclones	O
+in	O
+the	O
+presence	O
+of	O
+beta	O
+-	O
+lactams	O
+.	O
+
+We	O
+hypothesized	O
+that	O
+regulation	O
+of	O
+methicillin	O
+resistance	O
+in	O
+such	O
+low	O
+-	O
+level	O
+resistant	O
+clonal	O
+lineages	O
+may	O
+differ	O
+qualitatively	O
+from	O
+classical	O
+heterogeneously	O
+-	O
+or	O
+highly	O
+-	O
+resistant	O
+MRSA	B
+.	O
+
+A	O
+DNA	O
+-	O
+binding	O
+protein	O
+purification	O
+assay	O
+was	O
+performed	O
+to	O
+identify	O
+new	O
+potential	O
+factors	O
+involved	O
+in	O
+the	O
+regulation	O
+of	O
+mecA	O
+/	O
+PBP2a	O
+.	O
+
+The	O
+mecA	O
+/	O
+mecR1	O
+intergenic	O
+DNA	O
+region	O
+,	O
+including	O
+the	O
+5	O
+'	O
+9	O
+bp	O
+of	O
+mecR1	O
+and	O
+the	O
+first	O
+52	O
+bp	O
+of	O
+mecA	O
+,	O
+was	O
+used	O
+as	O
+bait	O
+against	O
+crude	O
+protein	O
+extract	O
+from	O
+strain	O
+CHE482	O
+.	O
+
+Proteins	O
+binding	O
+to	O
+this	O
+DNA	O
+fragment	O
+were	O
+analysed	O
+by	O
+SDS	O
+-	O
+PAGE	O
+.	O
+
+Even	O
+though	O
+CHE482	O
+contained	O
+BlaI	O
+,	O
+which	O
+is	O
+known	O
+to	O
+bind	O
+to	O
+the	O
+mec	O
+operator	O
+,	O
+this	O
+band	O
+could	O
+not	O
+be	O
+identified	O
+on	O
+gels	O
+due	O
+to	O
+co	O
+-	O
+migrating	O
+,	O
+non	O
+-	O
+specific	O
+bands	O
+the	O
+same	O
+size	O
+as	O
+BlaI	O
+(	O
+14	O
+.	O
+9	O
+KDa	O
+)	O
+that	O
+bound	O
+to	O
+both	O
+the	O
+DNA	O
+-	O
+coated	O
+and	O
+uncoated	O
+control	O
+beads	O
+.	O
+
+The	O
+most	O
+prominent	O
+protein	O
+band	O
+of	O
+~	O
+16	O
+-	O
+20	O
+kDa	O
+,	O
+isolated	O
+from	O
+DNA	O
+-	O
+labelled	O
+but	O
+not	O
+from	O
+control	O
+beads	O
+,	O
+was	O
+identified	O
+as	O
+the	O
+hypothetical	O
+protein	O
+SA1665	O
+(	O
+N315	O
+genome	O
+annotation	O
+[	O
+BA000018	O
+]	O
+)	O
+(	O
+Figure	O
+1A	O
+)	O
+.	O
+
+SA1665	O
+encodes	O
+a	O
+predicted	O
+17	O
+-	O
+kDa	O
+protein	O
+with	O
+an	O
+n	O
+-	O
+terminal	O
+helix	O
+-	O
+turn	O
+-	O
+helix	O
+(	O
+HTH	O
+)	O
+motif	O
+characteristic	O
+of	O
+DNA	O
+-	O
+binding	O
+transcriptional	O
+regulators	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequence	O
+of	O
+SA1665	O
+showed	O
+100	O
+%	O
+identity	O
+amongst	O
+S	B
+.	I
+aureus	I
+database	O
+sequences	O
+and	O
+97	O
+-	O
+98	O
+%	O
+identity	O
+amongst	O
+other	O
+staphylococci	O
+,	O
+including	O
+S	B
+.	I
+haemolyticus	I
+,	O
+S	B
+.	I
+epidermidis	I
+and	O
+S	B
+.	I
+saprophyticus	I
+,	O
+indicating	O
+that	O
+SA1665	O
+is	O
+highly	O
+conserved	O
+.	O
+
+Conversely	O
+,	O
+there	O
+were	O
+no	O
+orfs	O
+highly	O
+similar	O
+to	O
+SA1665	O
+found	O
+in	O
+other	O
+bacterial	O
+species	O
+,	O
+with	O
+the	O
+most	O
+similar	O
+sequences	O
+found	O
+in	O
+Bacillus	B
+licheniformis	I
+DSM13	O
+and	O
+Desulfitobacterium	B
+hafniense	I
+Y51	I
+,	O
+which	O
+shared	O
+only	O
+64	O
+%	O
+and	O
+59	O
+%	O
+similarity	O
+,	O
+respectively	O
+.	O
+
+Electro	O
+mobility	O
+shift	O
+assays	O
+(	O
+EMSA	O
+)	O
+
+EMSA	O
+was	O
+used	O
+to	O
+confirm	O
+binding	O
+of	O
+SA1665	O
+to	O
+the	O
+mec	O
+operator	O
+region	O
+.	O
+
+Crude	O
+protein	O
+extracts	O
+of	O
+E	B
+.	I
+coli	I
+strain	I
+BL21	I
+,	O
+carrying	O
+the	O
+empty	O
+plasmid	O
+(	O
+pET28nHis6	O
+)	O
+or	O
+pME20	O
+(	O
+pET28nHis6	O
+-	O
+SA1665	O
+)	O
+which	O
+expressed	O
+nHis6	O
+-	O
+SA1665	O
+upon	O
+induction	O
+with	O
+IPTG	O
+,	O
+were	O
+incubated	O
+with	O
+the	O
+161	O
+-	O
+bp	O
+biotinylated	O
+-	O
+DNA	O
+fragment	O
+previously	O
+used	O
+as	O
+bait	O
+in	O
+the	O
+DNA	O
+-	O
+binding	O
+protein	O
+assay	O
+.	O
+
+A	O
+band	O
+shift	O
+was	O
+observed	O
+with	O
+extracts	O
+from	O
+the	O
+strain	O
+expressing	O
+recombinant	O
+nHis6	O
+-	O
+SA1665	O
+but	O
+not	O
+from	O
+the	O
+control	O
+strain	O
+carrying	O
+the	O
+empty	O
+plasmid	O
+.	O
+
+Several	O
+bands	O
+resulted	O
+from	O
+the	O
+shift	O
+,	O
+which	O
+is	O
+most	O
+likely	O
+due	O
+to	O
+protein	O
+oligomerisation	O
+(	O
+Figure	O
+2A	O
+)	O
+.	O
+
+The	O
+specificity	O
+of	O
+the	O
+gel	O
+shift	O
+was	O
+also	O
+demonstrated	O
+by	O
+the	O
+addition	O
+of	O
+increasing	O
+concentrations	O
+of	O
+purified	O
+nHis6	O
+-	O
+SA1665	O
+protein	O
+to	O
+the	O
+biotinylated	O
+-	O
+DNA	O
+fragment	O
+(	O
+Figure	O
+2B	O
+)	O
+.	O
+
+Band	O
+-	O
+shift	O
+of	O
+the	O
+biotinylated	O
+DNA	O
+was	O
+inhibited	O
+in	O
+the	O
+presence	O
+of	O
+specific	O
+competitor	O
+DNA	O
+but	O
+not	O
+by	O
+the	O
+presence	O
+of	O
+the	O
+non	O
+-	O
+specific	O
+competitor	O
+DNA	O
+,	O
+confirming	O
+that	O
+nHis6	O
+-	O
+SA1665	O
+had	O
+a	O
+specific	O
+binding	O
+affinity	O
+for	O
+the	O
+161	O
+-	O
+bp	O
+DNA	O
+fragment	O
+.	O
+
+Effect	O
+of	O
+SA1665	O
+deletion	O
+on	O
+beta	O
+-	O
+lactam	O
+resistance	O
+
+To	O
+analyse	O
+the	O
+effect	O
+of	O
+SA1665	O
+inactivation	O
+on	O
+methicillin	O
+resistance	O
+,	O
+nonpolar	O
+markerless	O
+deletions	O
+of	O
+SA1665	O
+(	O
+Figure	O
+1B	O
+)	O
+were	O
+constructed	O
+in	O
+a	O
+selection	O
+of	O
+clinical	O
+MRSA	B
+isolates	O
+,	O
+which	O
+varied	O
+in	O
+their	O
+genetic	O
+background	O
+,	O
+SCCmec	O
+type	O
+,	O
+and	O
+mecA	O
+regulation	O
+[	O
+24	O
+]	O
+.	O
+
+Strain	O
+CHE482	O
+,	O
+belongs	O
+to	O
+clonal	O
+complex	O
+CC45	O
+and	O
+sequence	O
+type	O
+ST45	O
+,	O
+and	O
+contains	O
+a	O
+novel	O
+SCCmec	O
+(	O
+SCCmecN1	O
+[	O
+23	O
+]	O
+)	O
+;	O
+while	O
+strains	O
+ZH37	O
+(	O
+CC45	O
+/	O
+ST45	O
+)	O
+and	O
+ZH73	O
+(	O
+CC22	O
+/	O
+ST22	O
+)	O
+contain	O
+type	O
+IV	O
+SCCmecs	O
+.	O
+
+All	O
+three	O
+of	O
+these	O
+strains	O
+have	O
+truncated	O
+mecI	O
+/	O
+mecR1	O
+regulatory	O
+loci	O
+but	O
+intact	O
+BlaI	O
+/	O
+BlaR1	O
+loci	O
+controlling	O
+mecA	O
+expression	O
+.	O
+
+Strain	O
+ZH44	O
+(	O
+CCT8	O
+/	O
+ST8	O
+)	O
+contained	O
+a	O
+type	O
+A	O
+mec	O
+complex	O
+(	O
+mecI	O
+-	O
+mecR1	O
+-	O
+mecA	O
+)	O
+within	O
+a	O
+type	O
+II	O
+SCCmec	O
+,	O
+and	O
+had	O
+no	O
+beta	O
+-	O
+lactamase	O
+locus	O
+;	O
+so	O
+mecA	O
+was	O
+only	O
+under	O
+the	O
+control	O
+of	O
+its	O
+cognate	O
+regulators	O
+MecI	O
+/	O
+MecR1	O
+.	O
+
+Deletion	O
+of	O
+SA1665	O
+increased	O
+oxacillin	O
+resistance	O
+in	O
+all	O
+mutants	O
+compared	O
+to	O
+their	O
+corresponding	O
+parent	O
+strains	O
+,	O
+as	O
+demonstrated	O
+on	O
+oxacillin	O
+gradient	O
+plates	O
+(	O
+Figure	O
+3A	O
+)	O
+;	O
+with	O
+mutants	O
+Delta	O
+CHE482	O
+and	O
+Delta	O
+ZH37	O
+approximately	O
+doubling	O
+in	O
+resistance	O
+and	O
+Delta	O
+ZH44	O
+and	O
+Delta	O
+ZH73	O
+expressing	O
+considerably	O
+higher	O
+resistance	O
+.	O
+
+Population	O
+analysis	O
+resistance	O
+profiles	O
+of	O
+the	O
+mutants	O
+showed	O
+a	O
+distinct	O
+shift	O
+at	O
+the	O
+top	O
+of	O
+the	O
+curve	O
+,	O
+indicating	O
+that	O
+the	O
+higher	O
+resistance	O
+was	O
+due	O
+to	O
+increased	O
+basal	O
+oxacillin	O
+resistance	O
+levels	O
+(	O
+Figure	O
+3B	O
+)	O
+.	O
+
+Strains	O
+CHE482	O
+/	O
+Delta	O
+CHE482	O
+and	O
+ZH37	O
+/	O
+Delta	O
+ZH37	O
+had	O
+very	O
+similar	O
+resistance	O
+profiles	O
+,	O
+despite	O
+having	O
+different	O
+SCCmec	O
+elements	O
+,	O
+suggesting	O
+that	O
+it	O
+was	O
+their	O
+common	O
+clonal	O
+background	O
+(	O
+CC45	O
+)	O
+that	O
+determined	O
+their	O
+resistance	O
+levels	O
+and	O
+the	O
+extent	O
+of	O
+resistance	O
+increase	O
+upon	O
+SA1665	O
+deletion	O
+.	O
+
+Growth	O
+curve	O
+analyses	O
+showed	O
+that	O
+deletion	O
+of	O
+SA1665	O
+slightly	O
+reduced	O
+the	O
+growth	O
+rate	O
+of	O
+all	O
+strains	O
+tested	O
+(	O
+Figure	O
+3C	O
+)	O
+.	O
+
+Wild	O
+type	O
+growth	O
+rates	O
+were	O
+restored	O
+upon	O
+complementation	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Resistance	O
+complementation	O
+
+Plasmids	O
+pME26	O
+and	O
+pME27	O
+were	O
+constructed	O
+for	O
+complementation	O
+of	O
+the	O
+deletion	O
+mutants	O
+.	O
+
+Both	O
+plasmids	O
+contained	O
+the	O
+SA1665	O
+orf	O
+along	O
+with	O
+its	O
+own	O
+promoter	O
+and	O
+transcriptional	O
+terminator	O
+.	O
+
+Strains	O
+Delta	O
+CHE482	O
+,	O
+Delta	O
+ZH37	O
+,	O
+and	O
+Delta	O
+ZH73	O
+were	O
+complemented	O
+with	O
+pME26	O
+,	O
+and	O
+intrinsically	O
+kanamycin	O
+resistant	O
+strain	O
+Delta	O
+ZH44	O
+was	O
+complemented	O
+with	O
+pME27	O
+.	O
+
+Wild	O
+type	O
+-	O
+like	O
+resistance	O
+levels	O
+were	O
+restored	O
+in	O
+all	O
+mutants	O
+by	O
+introduction	O
+of	O
+the	O
+complementing	O
+plasmids	O
+,	O
+as	O
+shown	O
+by	O
+gradient	O
+plates	O
+(	O
+Figure	O
+3A	O
+)	O
+.	O
+
+Transcriptional	O
+analyses	O
+
+Primer	O
+extension	O
+,	O
+using	O
+the	O
+5	O
+'	O
+-	O
+biotinylated	O
+primer	O
+me97	O
+,	O
+identified	O
+two	O
+potential	O
+SA1665	O
+transcriptional	O
+start	O
+sites	O
+(	O
+TSS	O
+)	O
+,	O
+76	O
+-	O
+nt	O
+and	O
+139	O
+-	O
+nt	O
+upstream	O
+of	O
+the	O
+SA1665	O
+ATG	O
+start	O
+codon	O
+(	O
+Figure	O
+4A	O
+)	O
+.	O
+
+Predicted	O
+sigma	O
+A	O
+promoter	O
+consensus	O
+-	O
+10	O
+/	O
+-	O
+35	O
+box	O
+sequences	O
+were	O
+located	O
+upstream	O
+of	O
+both	O
+TSS	O
+(	O
+Figure	O
+4B	O
+)	O
+.	O
+
+Identical	O
+TSS	O
+were	O
+also	O
+identified	O
+using	O
+the	O
+downstream	O
+primer	O
+me98	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+was	O
+used	O
+to	O
+investigate	O
+SA1665	O
+expression	O
+and	O
+the	O
+influence	O
+of	O
+SA1665	O
+deletion	O
+on	O
+mecA	O
+and	O
+mecR1	O
+transcription	O
+.	O
+
+RNA	O
+samples	O
+taken	O
+from	O
+different	O
+time	O
+points	O
+over	O
+the	O
+growth	O
+curve	O
+of	O
+CHE482	O
+showed	O
+that	O
+SA1665	O
+was	O
+expressed	O
+strongly	O
+in	O
+early	O
+exponential	O
+phase	O
+at	O
+OD600	O
+nm	O
+0	O
+.	O
+25	O
+and	O
+0	O
+.	O
+5	O
+,	O
+then	O
+transcript	O
+levels	O
+decreased	O
+and	O
+were	O
+almost	O
+undetectable	O
+in	O
+early	O
+stationary	O
+phase	O
+at	O
+OD600	O
+nm	O
+4	O
+.	O
+0	O
+(	O
+Figure	O
+5A	O
+)	O
+.	O
+
+In	O
+addition	O
+to	O
+the	O
+main	O
+transcript	O
+of	O
+~	O
+0	O
+.	O
+46	O
+kb	O
+,	O
+a	O
+weaker	O
+,	O
+larger	O
+transcript	O
+of	O
+~	O
+0	O
+.	O
+6	O
+kb	O
+was	O
+also	O
+visible	O
+,	O
+especially	O
+at	O
+later	O
+growth	O
+stages	O
+.	O
+
+Figure	O
+5B	O
+shows	O
+the	O
+transcriptional	O
+behaviour	O
+of	O
+SA1665	O
+when	O
+CHE482	O
+cells	O
+were	O
+challenged	O
+with	O
+sub	O
+-	O
+inhibitory	O
+(	O
+4	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+and	O
+inhibitory	O
+(	O
+120	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+concentrations	O
+of	O
+cefoxitin	O
+.	O
+
+These	O
+results	O
+showed	O
+that	O
+low	O
+levels	O
+of	O
+cefoxitin	O
+,	O
+such	O
+as	O
+those	O
+used	O
+to	O
+induce	O
+mecA	O
+/	O
+mecR1	O
+transcription	O
+,	O
+appeared	O
+to	O
+slightly	O
+decrease	O
+SA1665	O
+transcription	O
+after	O
+30	O
+min	O
+exposure	O
+,	O
+while	O
+larger	O
+,	O
+inhibitory	O
+concentrations	O
+caused	O
+even	O
+more	O
+significant	O
+alterations	O
+in	O
+the	O
+SA1665	O
+transcriptional	O
+profile	O
+,	O
+making	O
+it	O
+similar	O
+to	O
+that	O
+normally	O
+seen	O
+in	O
+stationary	O
+phase	O
+growth	O
+.	O
+
+These	O
+results	O
+indicate	O
+that	O
+transcription	O
+of	O
+SA1665	O
+may	O
+respond	O
+in	O
+some	O
+way	O
+to	O
+cell	O
+wall	O
+stress	O
+,	O
+rather	O
+than	O
+in	O
+direct	O
+response	O
+to	O
+the	O
+presence	O
+of	O
+beta	O
+-	O
+lactams	O
+.	O
+
+This	O
+observation	O
+is	O
+based	O
+on	O
+relatively	O
+subtle	O
+changes	O
+in	O
+SA1665	O
+transcription	O
+,	O
+especially	O
+at	O
+low	O
+concentrations	O
+of	O
+cefoxitin	O
+such	O
+as	O
+those	O
+required	O
+for	O
+mecA	O
+/	O
+mecR1	O
+induction	O
+.	O
+
+Since	O
+deletion	O
+of	O
+SA1665	O
+has	O
+been	O
+shown	O
+to	O
+increase	O
+beta	O
+-	O
+lactam	O
+resistance	O
+,	O
+reduced	O
+SA1665	O
+transcription	O
+in	O
+the	O
+presence	O
+of	O
+beta	O
+-	O
+lactams	O
+may	O
+also	O
+provide	O
+some	O
+protection	O
+against	O
+beta	O
+-	O
+lactam	O
+exposure	O
+.	O
+
+Northerns	O
+also	O
+showed	O
+that	O
+,	O
+as	O
+expected	O
+,	O
+the	O
+SA1665	O
+transcripts	O
+were	O
+absent	O
+from	O
+the	O
+deletion	O
+mutant	O
+(	O
+Figure	O
+5C	O
+)	O
+,	O
+and	O
+additional	O
+experiments	O
+demonstrated	O
+that	O
+wild	O
+type	O
+SA1665	O
+transcription	O
+patterns	O
+were	O
+restored	O
+by	O
+complementation	O
+of	O
+Delta	O
+CHE482	O
+with	O
+pME26	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+The	O
+effects	O
+of	O
+SA1665	O
+deletion	O
+on	O
+directly	O
+up	O
+-	O
+and	O
+down	O
+-	O
+stream	O
+genes	O
+were	O
+also	O
+investigated	O
+.	O
+
+Northern	O
+blots	O
+of	O
+the	O
+neighbouring	O
+genes	O
+SA1664	O
+,	O
+SA1666	O
+and	O
+SA1667	O
+,	O
+showed	O
+that	O
+expression	O
+of	O
+all	O
+three	O
+genes	O
+was	O
+very	O
+weak	O
+compared	O
+to	O
+that	O
+of	O
+SA1665	O
+.	O
+
+A	O
+weak	O
+transcript	O
+of	O
+about	O
+3	O
+kb	O
+was	O
+present	O
+in	O
+hybridizations	O
+probed	O
+with	O
+orfs	O
+SA1665	O
+-	O
+SA1667	O
+.	O
+
+This	O
+band	O
+decreased	O
+in	O
+size	O
+in	O
+the	O
+SA1665	O
+mutant	O
+when	O
+probed	O
+with	O
+SA1666	O
+and	O
+SA1667	O
+.	O
+
+One	O
+of	O
+the	O
+transcripts	O
+hybridising	O
+to	O
+the	O
+SA1664	O
+probe	O
+also	O
+decreased	O
+in	O
+size	O
+by	O
+~	O
+0	O
+.	O
+5	O
+kb	O
+in	O
+the	O
+SA1665	O
+mutant	O
+,	O
+suggesting	O
+that	O
+SA1665	O
+was	O
+present	O
+on	O
+several	O
+transcripts	O
+of	O
+different	O
+lengths	O
+,	O
+including	O
+a	O
+high	O
+abundance	O
+monocistronic	O
+transcript	O
+and	O
+low	O
+abundance	O
+polycistronic	O
+transcripts	O
+(	O
+Figure	O
+5C	O
+)	O
+.	O
+
+Transcript	O
+abundance	O
+of	O
+both	O
+the	O
+upstream	O
+SA1666	O
+-	O
+SA1667	O
+operon	O
+and	O
+the	O
+downstream	O
+SA1664	O
+-	O
+specific	O
+transcript	O
+all	O
+appeared	O
+to	O
+increase	O
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+in	O
+Delta	O
+CHE482	O
+.	O
+
+The	O
+significance	O
+of	O
+these	O
+subtle	O
+increases	O
+in	O
+transcription	O
+are	O
+unknown	O
+,	O
+however	O
+,	O
+polar	O
+effects	O
+from	O
+SA1665	O
+deletion	O
+seem	O
+unlikely	O
+,	O
+based	O
+on	O
+the	O
+facts	O
+that	O
+all	O
+genes	O
+were	O
+still	O
+transcribed	O
+,	O
+their	O
+transcription	O
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+all	O
+remained	O
+extremely	O
+low	O
+and	O
+the	O
+transcriptional	O
+terminator	O
+of	O
+SA1665	O
+remained	O
+intact	O
+in	O
+the	O
+deletion	O
+mutant	O
+(	O
+Figure	O
+1B	O
+)	O
+.	O
+
+Expression	O
+of	O
+mecR1	O
+and	O
+mecA	O
+were	O
+analysed	O
+from	O
+RNA	O
+of	O
+uninduced	O
+and	O
+induced	O
+cultures	O
+of	O
+CHE482	O
+and	O
+Delta	O
+CHE482	O
+.	O
+
+Cells	O
+were	O
+induced	O
+at	O
+OD600	O
+nm	O
+0	O
+.	O
+25	O
+(	O
+Figure	O
+5D	O
+)	O
+and	O
+1	O
+.	O
+0	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+with	O
+sub	O
+-	O
+inhibitory	O
+concentrations	O
+of	O
+cefoxitin	O
+,	O
+to	O
+relieve	O
+BlaI	O
+-	O
+repression	O
+of	O
+mecA	O
+.	O
+
+mecR1	O
+,	O
+although	O
+truncated	O
+in	O
+CHE482	O
+,	O
+was	O
+still	O
+transcribed	O
+and	O
+had	O
+the	O
+same	O
+expression	O
+pattern	O
+as	O
+mecA	O
+,	O
+as	O
+both	O
+became	O
+derepressed	O
+over	O
+time	O
+and	O
+had	O
+the	O
+highest	O
+transcript	O
+levels	O
+after	O
+30	O
+min	O
+of	O
+induction	O
+.	O
+
+In	O
+the	O
+mutant	O
+Delta	O
+CHE482	O
+,	O
+transcripts	O
+of	O
+both	O
+mecA	O
+and	O
+mecR1	O
+'	O
+were	O
+unaffected	O
+by	O
+SA1665	O
+deletion	O
+,	O
+indicating	O
+that	O
+SA1665	O
+had	O
+no	O
+influence	O
+on	O
+their	O
+expression	O
+at	O
+either	O
+OD	O
+0	O
+.	O
+25	O
+(	O
+Figure	O
+5D	O
+)	O
+or	O
+OD	O
+1	O
+.	O
+0	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+SA1665	O
+deletion	O
+also	O
+had	O
+no	O
+effect	O
+on	O
+mecA	O
+transcription	O
+or	O
+induction	O
+in	O
+strains	O
+ZH37	O
+,	O
+ZH44	O
+and	O
+ZH73	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+
+Mutants	O
+of	O
+CHE482	O
+and	O
+of	O
+ZH44	O
+and	O
+ZH73	O
+,	O
+which	O
+had	O
+the	O
+largest	O
+differences	O
+in	O
+oxacillin	O
+resistance	O
+levels	O
+,	O
+were	O
+analysed	O
+by	O
+Western	O
+blot	O
+analysis	O
+to	O
+determine	O
+if	O
+SA1665	O
+affected	O
+production	O
+of	O
+PBP2a	O
+from	O
+mecA	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+5E	O
+,	O
+all	O
+pairs	O
+of	O
+wild	O
+type	O
+and	O
+mutant	O
+strains	O
+had	O
+similar	O
+amounts	O
+of	O
+PBP2a	O
+present	O
+both	O
+before	O
+and	O
+after	O
+induction	O
+with	O
+cefoxitin	O
+,	O
+indicating	O
+that	O
+SA1665	O
+deletion	O
+did	O
+not	O
+alter	O
+amounts	O
+of	O
+PBP2a	O
+produced	O
+.	O
+
+Therefore	O
+it	O
+seems	O
+that	O
+SA1665	O
+exerts	O
+no	O
+direct	O
+control	O
+over	O
+mecA	O
+or	O
+PBP2a	O
+expression	O
+.	O
+
+Discussion	O
+
+Methicillin	O
+resistance	O
+in	O
+MRSA	B
+is	O
+primarily	O
+dependent	O
+on	O
+the	O
+presence	O
+of	O
+the	O
+mecA	O
+gene	O
+,	O
+however	O
+,	O
+resistance	O
+levels	O
+are	O
+generally	O
+governed	O
+by	O
+strain	O
+-	O
+specific	O
+factors	O
+including	O
+mecA	O
+regulatory	O
+elements	O
+and	O
+other	O
+chromosomal	O
+fem	O
+/	O
+aux	O
+factors	O
+which	O
+either	O
+enhance	O
+or	O
+repress	O
+the	O
+expression	O
+of	O
+resistance	O
+.	O
+
+For	O
+instance	O
+,	O
+the	O
+very	O
+low	O
+-	O
+level	O
+methicillin	O
+resistance	O
+of	O
+the	O
+Zurich	O
+drug	O
+clone	O
+CHE482	O
+,	O
+was	O
+shown	O
+to	O
+be	O
+controlled	O
+by	O
+its	O
+genetic	O
+background	O
+[	O
+12	O
+]	O
+suggesting	O
+that	O
+it	O
+either	O
+contained	O
+or	O
+lacked	O
+certain	O
+fem	O
+/	O
+aux	O
+factors	O
+involved	O
+in	O
+controlling	O
+resistance	O
+expression	O
+.	O
+
+Many	O
+of	O
+the	O
+currently	O
+known	O
+fem	O
+/	O
+aux	O
+factors	O
+are	O
+directly	O
+or	O
+indirectly	O
+involved	O
+in	O
+cell	O
+wall	O
+synthesis	O
+and	O
+turnover	O
+,	O
+or	O
+envelope	O
+biogenesis	O
+,	O
+however	O
+there	O
+still	O
+remain	O
+factors	O
+of	O
+unknown	O
+function	O
+.	O
+
+Most	O
+of	O
+the	O
+currently	O
+known	O
+fem	O
+/	O
+aux	O
+factors	O
+reduce	O
+methicillin	O
+resistance	O
+levels	O
+when	O
+inactivated	O
+.	O
+
+A	O
+few	O
+genes	O
+,	O
+such	O
+as	O
+lytH	O
+,	O
+dlt	O
+,	O
+norG	O
+,	O
+sarV	O
+and	O
+cidA	O
+increase	O
+resistance	O
+levels	O
+upon	O
+inactivation	O
+or	O
+mutation	O
+.	O
+
+All	O
+of	O
+these	O
+genes	O
+,	O
+except	O
+norG	O
+,	O
+which	O
+is	O
+an	O
+efflux	O
+pump	O
+regulator	O
+,	O
+play	O
+a	O
+role	O
+in	O
+either	O
+autolysis	O
+or	O
+are	O
+important	O
+for	O
+cell	O
+physiology	O
+and	O
+growth	O
+[	O
+25	O
+-	O
+30	O
+]	O
+.	O
+
+Other	O
+genes	O
+increase	O
+beta	O
+-	O
+lactam	O
+resistance	O
+upon	O
+overexpression	O
+,	O
+such	O
+as	O
+hmrA	O
+coding	O
+for	O
+a	O
+putative	O
+amidohydrolase	O
+,	O
+hmrB	O
+coding	O
+for	O
+a	O
+putative	O
+acyl	O
+carrier	O
+protein	O
+[	O
+31	O
+]	O
+,	O
+or	O
+the	O
+NorG	O
+-	O
+controlled	O
+abcA	O
+multidrug	O
+efflux	O
+pump	O
+[	O
+28	O
+]	O
+.	O
+
+SA1665	O
+,	O
+a	O
+predicted	O
+DNA	O
+-	O
+binding	O
+transcriptional	O
+regulator	O
+,	O
+was	O
+found	O
+to	O
+bind	O
+to	O
+a	O
+DNA	O
+fragment	O
+containing	O
+the	O
+mecA	O
+promoter	O
+region	O
+.	O
+
+However	O
+,	O
+although	O
+this	O
+protein	O
+shifted	O
+the	O
+mecA	O
+operator	O
+/	O
+5	O
+'	O
+coding	O
+sequence	O
+,	O
+it	O
+did	O
+not	O
+appear	O
+to	O
+directly	O
+control	O
+mecA	O
+or	O
+mecR1	O
+transcription	O
+or	O
+PBP2a	O
+production	O
+.	O
+
+Therefore	O
+its	O
+binding	O
+to	O
+the	O
+mecA	O
+region	O
+may	O
+have	O
+no	O
+specific	O
+regulatory	O
+function	O
+.	O
+
+Such	O
+interactions	O
+have	O
+been	O
+noted	O
+before	O
+,	O
+such	O
+as	O
+the	O
+HTH	O
+protein	O
+NorG	O
+,	O
+which	O
+was	O
+shown	O
+to	O
+bind	O
+specifically	O
+to	O
+norA	O
+,	O
+norB	O
+and	O
+norC	O
+promoters	O
+,	O
+but	O
+only	O
+transcription	O
+of	O
+norB	O
+was	O
+increased	O
+when	O
+NorG	O
+was	O
+overexpressed	O
+[	O
+28	O
+]	O
+.	O
+
+We	O
+have	O
+to	O
+postulate	O
+therefore	O
+that	O
+SA1665	O
+may	O
+modulate	O
+beta	O
+-	O
+lactam	O
+resistance	O
+in	O
+a	O
+mecA	O
+-	O
+independent	O
+manner	O
+,	O
+by	O
+controlling	O
+cellular	O
+functions	O
+affecting	O
+resistance	O
+levels	O
+.	O
+
+Experiments	O
+to	O
+determine	O
+the	O
+SA1665	O
+regulon	O
+are	O
+ongoing	O
+.	O
+
+The	O
+impact	O
+of	O
+deleting	O
+SA1665	O
+in	O
+MRSA	B
+was	O
+extremely	O
+strain	O
+specific	O
+,	O
+underlining	O
+the	O
+importance	O
+of	O
+the	O
+genetic	O
+background	O
+in	O
+governing	O
+the	O
+final	O
+methicillin	O
+resistance	O
+levels	O
+of	O
+MRSA	B
+,	O
+and	O
+demonstrating	O
+the	O
+large	O
+genomic	O
+variability	O
+between	O
+different	O
+strain	O
+lineages	O
+.	O
+
+Conclusion	O
+
+SA1665	O
+is	O
+a	O
+previously	O
+uncharacterised	O
+DNA	O
+-	O
+binding	O
+protein	O
+that	O
+has	O
+a	O
+negative	O
+effect	O
+on	O
+beta	O
+-	O
+lactam	O
+resistance	O
+in	O
+MRSA	B
+.	O
+
+The	O
+SA1665	O
+protein	O
+was	O
+identified	O
+in	O
+a	O
+DNA	O
+-	O
+binding	O
+protein	O
+purification	O
+assay	O
+,	O
+in	O
+which	O
+it	O
+bound	O
+to	O
+a	O
+DNA	O
+fragment	O
+covering	O
+the	O
+mec	O
+operator	O
+region	O
+.	O
+
+However	O
+,	O
+while	O
+nonpolar	O
+deletion	O
+of	O
+SA1665	O
+was	O
+shown	O
+to	O
+increase	O
+oxacillin	O
+resistance	O
+levels	O
+in	O
+several	O
+heterogeneously	O
+resistant	O
+MRSA	B
+,	O
+its	O
+deletion	O
+had	O
+no	O
+effect	O
+on	O
+mecA	O
+transcription	O
+or	O
+PBP2a	O
+production	O
+.	O
+
+Therefore	O
+the	O
+negative	O
+impact	O
+of	O
+SA1665	O
+on	O
+methicillin	O
+resistance	O
+is	O
+most	O
+likely	O
+to	O
+be	O
+through	O
+the	O
+regulation	O
+of	O
+other	O
+chromosomal	O
+factors	O
+or	O
+cellular	O
+functions	O
+required	O
+for	O
+methicllin	O
+resistance	O
+.	O
+
+Methods	O
+
+Strains	O
+and	O
+growth	O
+conditions	O
+
+Strains	O
+and	O
+plasmids	O
+used	O
+in	O
+this	O
+study	O
+are	O
+listed	O
+in	O
+Table	O
+1	O
+.	O
+
+Clinical	O
+isolates	O
+are	O
+from	O
+the	O
+IMM	O
+collection	O
+in	O
+Zurich	O
+,	O
+Switzerland	O
+.	O
+
+Strains	O
+were	O
+grown	O
+at	O
+37	O
+degrees	O
+C	O
+in	O
+Luria	O
+Bertani	O
+(	O
+LB	O
+)	O
+broth	O
+,	O
+shaking	O
+at	O
+180	O
+rpm	O
+,	O
+or	O
+on	O
+LB	O
+agar	O
+.	O
+
+Media	O
+were	O
+supplemented	O
+with	O
+the	O
+following	O
+antibiotics	O
+when	O
+appropriate	O
+:	O
+25	O
+or	O
+50	O
+mu	O
+g	O
+/	O
+ml	O
+kanamycin	O
+,	O
+10	O
+mu	O
+g	O
+/	O
+ml	O
+chloramphenicol	O
+,	O
+5	O
+or	O
+10	O
+mu	O
+g	O
+/	O
+ml	O
+tetracycline	O
+,	O
+100	O
+mu	O
+g	O
+/	O
+ml	O
+ampicillin	O
+.	O
+
+Concentrations	O
+of	O
+cefoxitin	O
+used	O
+for	O
+transcriptional	O
+induction	O
+were	O
+either	O
+sub	O
+-	O
+inhibitory	O
+(	O
+4	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+or	O
+inhibitory	O
+(	O
+120	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+.	O
+
+Susceptibility	O
+testing	O
+
+Oxacillin	O
+resistance	O
+levels	O
+were	O
+compared	O
+by	O
+swabbing	O
+0	O
+.	O
+5	O
+McFarland	O
+cell	O
+suspensions	O
+across	O
+agar	O
+plates	O
+containing	O
+appropriate	O
+concentration	O
+gradients	O
+of	O
+oxacillin	O
+.	O
+
+For	O
+population	O
+analysis	O
+profiles	O
+,	O
+appropriate	O
+dilutions	O
+of	O
+an	O
+overnight	O
+culture	O
+,	O
+ranging	O
+from	O
+100	O
+to	O
+108	O
+,	O
+were	O
+plated	O
+on	O
+increasing	O
+concentrations	O
+of	O
+oxacillin	O
+.	O
+
+Plates	O
+were	O
+incubated	O
+at	O
+35	O
+degrees	O
+C	O
+and	O
+colony	O
+forming	O
+units	O
+per	O
+ml	O
+(	O
+cfu	O
+/	O
+ml	O
+)	O
+were	O
+determined	O
+after	O
+48	O
+h	O
+.	O
+
+Binding	O
+-	O
+protein	O
+purification	O
+
+Crude	O
+protein	O
+extracts	O
+were	O
+isolated	O
+from	O
+CHE482	O
+,	O
+grown	O
+under	O
+normal	O
+culture	O
+conditions	O
+until	O
+OD600	O
+nm	O
+1	O
+.	O
+5	O
+.	O
+
+Cells	O
+were	O
+harvested	O
+,	O
+resuspended	O
+in	O
+PBS	O
+(	O
+pH	O
+7	O
+.	O
+4	O
+)	O
+and	O
+mechanically	O
+lysed	O
+using	O
+Lysing	O
+Matrix	O
+B	O
+(	O
+BIO	O
+101	O
+Systems	O
+)	O
+tubes	O
+and	O
+a	O
+FastPrep	O
+FP120	O
+(	O
+BIO	O
+101	O
+Systems	O
+)	O
+.	O
+
+Suspensions	O
+were	O
+clarified	O
+by	O
+centrifugation	O
+and	O
+supernatants	O
+,	O
+containing	O
+soluble	O
+cytoplasmic	O
+proteins	O
+,	O
+were	O
+transferred	O
+to	O
+Amicon	O
+Ultra	O
+centrifugal	O
+filter	O
+devices	O
+(	O
+Millipore	O
+)	O
+with	O
+a	O
+pore	O
+cut	O
+-	O
+off	O
+size	O
+of	O
+10	O
+kDa	O
+.	O
+
+Proteins	O
+were	O
+then	O
+washed	O
+and	O
+concentrated	O
+in	O
+1	O
+x	O
+binding	O
+buffer	O
+(	O
+10	O
+mM	O
+Tris	O
+-	O
+HCl	O
+,	O
+pH	O
+7	O
+.	O
+5	O
+,	O
+1	O
+mM	O
+EDTA	O
+,	O
+and	O
+1	O
+mM	O
+DTT	O
+,	O
+0	O
+.	O
+5	O
+M	O
+NaCl	O
+)	O
+.	O
+
+Protein	O
+concentrations	O
+were	O
+measured	O
+by	O
+Bradford	O
+assay	O
+(	O
+BioRad	O
+Laboratories	O
+GmbH	O
+)	O
+[	O
+32	O
+]	O
+.	O
+
+Primer	O
+pair	O
+me36F	O
+/	O
+me36Rbiot	O
+(	O
+Table	O
+2	O
+)	O
+were	O
+used	O
+to	O
+amplify	O
+a	O
+biotinylated	O
+mecA	O
+promoter	O
+/	O
+operator	O
+fragment	O
+,	O
+which	O
+was	O
+bound	O
+to	O
+streptavidin	O
+coated	O
+magnetic	O
+beads	O
+(	O
+Dynabeads	O
+M	O
+-	O
+280	O
+Streptavidin	O
+,	O
+DYNAL	O
+BIOTECH	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+.	O
+
+Binding	O
+reactions	O
+,	O
+containing	O
+DNA	O
+-	O
+coated	O
+beads	O
+mixed	O
+with	O
+100	O
+mu	O
+g	O
+of	O
+crude	O
+protein	O
+extract	O
+in	O
+1	O
+x	O
+protein	O
+binding	O
+buffer	O
+(	O
+20	O
+mM	O
+Hepes	O
+,	O
+pH	O
+7	O
+.	O
+6	O
+,	O
+1	O
+mM	O
+EDTA	O
+,	O
+10	O
+mM	O
+(	O
+NH4	O
+)	O
+2SO4	O
+,	O
+1	O
+mM	O
+DTT	O
+,	O
+0	O
+.	O
+2	O
+%	O
+Tween	O
+20	O
+(	O
+w	O
+/	O
+v	O
+)	O
+,	O
+30	O
+mM	O
+KCl	O
+)	O
+,	O
+0	O
+.	O
+02	O
+mu	O
+g	O
+/	O
+mu	O
+l	O
+poly	O
+d	O
+(	O
+I	O
+-	O
+C	O
+)	O
+and	O
+2	O
+ng	O
+/	O
+mu	O
+l	O
+poly	O
+L	O
+-	O
+lysine	O
+,	O
+were	O
+incubated	O
+at	O
+room	O
+temperature	O
+for	O
+30	O
+min	O
+with	O
+constant	O
+rotation	O
+.	O
+
+Beads	O
+were	O
+then	O
+washed	O
+and	O
+binding	O
+-	O
+proteins	O
+eluted	O
+in	O
+elution	O
+buffer	O
+(	O
+1	O
+x	O
+protein	O
+binding	O
+buffer	O
+containing	O
+2	O
+M	O
+KCl	O
+)	O
+.	O
+
+Eluted	O
+proteins	O
+were	O
+dialysed	O
+against	O
+water	O
+,	O
+concentrated	O
+by	O
+evaporation	O
+,	O
+and	O
+run	O
+on	O
+15	O
+%	O
+SDS	O
+polyacrylamide	O
+gels	O
+.	O
+
+Gels	O
+were	O
+silver	O
+stained	O
+using	O
+the	O
+Protein	O
+Silver	O
+Staining	O
+kit	O
+(	O
+Amersham	O
+Biosciences	O
+AB	O
+)	O
+without	O
+the	O
+addition	O
+of	O
+glutaraldehyde	O
+.	O
+
+Protein	O
+bands	O
+were	O
+excised	O
+from	O
+gels	O
+and	O
+analysed	O
+by	O
+mass	O
+spectrometry	O
+(	O
+LC	O
+/	O
+ESI	O
+/	O
+MS	O
+/	O
+MS	O
+)	O
+at	O
+the	O
+Functional	O
+Genomics	O
+Centre	O
+,	O
+Zurich	O
+.	O
+
+The	O
+SA1665	O
+protein	O
+sequence	O
+[	O
+BAB42933	O
+]	O
+was	O
+analysed	O
+by	O
+Blast	O
+search	O
+and	O
+motif	O
+scan	O
+.	O
+
+Expression	O
+of	O
+recombinant	O
+SA1665	O
+protein	O
+
+SA1665	O
+was	O
+amplified	O
+using	O
+primer	O
+pair	O
+me65BamHI	O
+/	O
+me65XhoI	O
+(	O
+Table	O
+2	O
+)	O
+and	O
+cloned	O
+in	O
+-	O
+frame	O
+into	O
+pET28nHis6	O
+(	O
+unpublished	O
+,	O
+D	O
+.	O
+Frey	O
+)	O
+.	O
+
+The	O
+resulting	O
+plasmid	O
+,	O
+pME20	O
+,	O
+was	O
+transformed	O
+into	O
+E	B
+.	I
+coli	I
+BL21	I
+for	O
+expression	O
+of	O
+recombinant	O
+nHis6	O
+-	O
+SA1665	O
+protein	O
+.	O
+
+To	O
+maximise	O
+the	O
+abundance	O
+of	O
+soluble	O
+protein	O
+produced	O
+,	O
+cultures	O
+were	O
+grown	O
+in	O
+osmotic	O
+shock	O
+medium	O
+at	O
+37	O
+degrees	O
+C	O
+(	O
+1	O
+g	O
+/	O
+l	O
+NaCl	O
+,	O
+16	O
+g	O
+/	O
+l	O
+tryptone	O
+,	O
+10	O
+g	O
+/	O
+l	O
+yeast	B
+,	O
+1	O
+M	O
+sorbitol	O
+,	O
+10	O
+mM	O
+betaine	O
+,	O
+modified	O
+from	O
+[	O
+33	O
+]	O
+)	O
+to	O
+an	O
+OD600	O
+nm	O
+of	O
+0	O
+.	O
+5	O
+,	O
+cooled	O
+briefly	O
+on	O
+ice	O
+,	O
+then	O
+induced	O
+by	O
+adding	O
+100	O
+mu	O
+M	O
+IPTG	O
+and	O
+growing	O
+overnight	O
+at	O
+22	O
+degrees	O
+C	O
+.	O
+
+Crude	O
+soluble	O
+proteins	O
+were	O
+extracted	O
+using	O
+CelLyticB	O
+2	O
+x	O
+cell	O
+lysis	O
+reagent	O
+(	O
+SIGMA	O
+)	O
+.	O
+
+HIS	O
+-	O
+Select	O
+Cobalt	O
+Affinity	O
+Gel	O
+(	O
+SIGMA	O
+)	O
+was	O
+used	O
+to	O
+purify	O
+recombinant	O
+nHis6	O
+-	O
+SA1665	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+instructions	O
+.	O
+
+Electro	O
+mobility	O
+shift	O
+assay	O
+
+For	O
+gel	O
+shift	O
+assays	O
+,	O
+6	O
+ng	O
+aliquots	O
+of	O
+the	O
+biotinylated	O
+-	O
+DNA	O
+fragment	O
+used	O
+for	O
+binding	O
+-	O
+protein	O
+purification	O
+were	O
+incubated	O
+with	O
+0	O
+-	O
+250	O
+ng	O
+of	O
+purified	O
+nHis6	O
+-	O
+SA1665	O
+protein	O
+in	O
+1	O
+x	O
+binding	O
+buffer	O
+(	O
+20	O
+mM	O
+Hepes	O
+pH	O
+7	O
+.	O
+6	O
+,	O
+1	O
+mM	O
+EDTA	O
+,	O
+10	O
+mM	O
+(	O
+NH4	O
+)	O
+2SO4	O
+,	O
+1	O
+mM	O
+DTT	O
+,	O
+0	O
+.	O
+2	O
+%	O
+Tween	O
+20	O
+(	O
+w	O
+/	O
+v	O
+)	O
+,	O
+30	O
+mM	O
+KCl	O
+)	O
+containing	O
+0	O
+.	O
+05	O
+mu	O
+g	O
+/	O
+mu	O
+l	O
+poly	O
+d	O
+(	O
+I	O
+-	O
+C	O
+)	O
+(	O
+Roche	O
+)	O
+and	O
+5	O
+ng	O
+/	O
+mu	O
+l	O
+poly	O
+L	O
+-	O
+lysine	O
+(	O
+Roche	O
+)	O
+.	O
+
+For	O
+control	O
+binding	O
+reactions	O
+,	O
+130	O
+x	O
+unlabelled	O
+mec	O
+operator	O
+DNA	O
+(	O
+amplified	O
+using	O
+primers	O
+me36F	O
+/	O
+me36R	O
+,	O
+Table	O
+2	O
+)	O
+was	O
+used	O
+as	O
+a	O
+specific	O
+binding	O
+competitor	O
+and	O
+6	O
+ng	O
+of	O
+herring	O
+sperm	O
+DNA	O
+was	O
+used	O
+as	O
+unspecific	O
+competitor	O
+DNA	O
+.	O
+
+Binding	O
+was	O
+carried	O
+out	O
+at	O
+22	O
+degrees	O
+C	O
+for	O
+30	O
+min	O
+.	O
+
+Samples	O
+were	O
+run	O
+on	O
+6	O
+%	O
+native	O
+polyacrylamide	O
+gels	O
+,	O
+contact	O
+blotted	O
+onto	O
+positively	O
+charged	O
+nylon	O
+membrane	O
+and	O
+detected	O
+with	O
+the	O
+Biotin	O
+Chromogenic	O
+Detection	O
+Kit	O
+(	O
+Fermentas	O
+)	O
+.	O
+
+Primer	O
+extension	O
+
+RNA	O
+was	O
+extracted	O
+from	O
+CHE482	O
+cultures	O
+that	O
+were	O
+grown	O
+to	O
+OD600	O
+nm	O
+0	O
+.	O
+5	O
+,	O
+as	O
+previously	O
+described	O
+[	O
+12	O
+]	O
+.	O
+
+Primer	O
+extension	O
+reactions	O
+were	O
+performed	O
+using	O
+20	O
+mu	O
+g	O
+of	O
+total	O
+RNA	O
+and	O
+3	O
+pmol	O
+of	O
+the	O
+5	O
+'	O
+-	O
+biotin	O
+-	O
+labelled	O
+primers	O
+me97	O
+and	O
+me98	O
+(	O
+Table	O
+2	O
+)	O
+using	O
+Superscript	O
+II	O
+reverse	O
+transcriptase	O
+(	O
+Invitrogen	O
+)	O
+,	O
+according	O
+to	O
+the	O
+manufacturers	O
+instructions	O
+.	O
+
+Sequencing	O
+reactions	O
+were	O
+performed	O
+using	O
+the	O
+Thermo	O
+Sequenase	O
+cycle	O
+sequencing	O
+kit	O
+(	O
+U	O
+.	O
+S	O
+.	O
+Biochemicals	O
+)	O
+.	O
+
+The	O
+Biotin	O
+Chromogenic	O
+Detection	O
+Kit	O
+(	O
+Fermentas	O
+)	O
+was	O
+used	O
+for	O
+biotin	O
+detection	O
+.	O
+
+Markerless	O
+deletion	O
+of	O
+SA1665	O
+
+In	O
+frame	O
+markerless	O
+deletions	O
+of	O
+SA1665	O
+,	O
+from	O
+the	O
+chromosomes	O
+of	O
+CHE482	O
+,	O
+ZH37	O
+,	O
+ZH44	O
+,	O
+and	O
+ZH73	O
+,	O
+were	O
+constructed	O
+using	O
+the	O
+pKOR1	O
+allelic	O
+replacement	O
+system	O
+,	O
+as	O
+described	O
+by	O
+Bae	O
+et	O
+al	O
+.	O
+
+[	O
+34	O
+]	O
+.	O
+
+Primer	O
+pairs	O
+used	O
+to	O
+amplify	O
+the	O
+DNA	O
+fragments	O
+flanking	O
+SA1665	O
+,	O
+for	O
+recombination	O
+into	O
+pKOR1	O
+were	O
+:	O
+me62attB1	O
+/	O
+me51BamHI	O
+and	O
+me62BamHI	O
+/	O
+me62attB2	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+All	O
+deletion	O
+mutants	O
+were	O
+confirmed	O
+by	O
+nucleotide	O
+sequencing	O
+over	O
+the	O
+deleted	O
+region	O
+,	O
+as	O
+well	O
+as	O
+by	O
+Southern	O
+blot	O
+analysis	O
+[	O
+35	O
+]	O
+and	O
+pulsed	O
+field	O
+gel	O
+electrophoresis	O
+(	O
+PFGE	O
+)	O
+[	O
+36	O
+]	O
+.	O
+
+Cloning	O
+of	O
+SA1665	O
+for	O
+complementation	O
+
+A	O
+1533	O
+-	O
+bp	O
+DNA	O
+fragment	O
+,	O
+containing	O
+SA1665	O
+together	O
+with	O
+690	O
+-	O
+bp	O
+of	O
+upstream	O
+and	O
+379	O
+-	O
+bp	O
+of	O
+downstream	O
+DNA	O
+,	O
+was	O
+amplified	O
+from	O
+strain	O
+CHE482	O
+using	O
+primers	O
+me94BamHI	O
+/	O
+me94Asp718	O
+(	O
+Table	O
+2	O
+)	O
+and	O
+cloned	O
+into	O
+the	O
+E	B
+.	I
+coli	I
+/	O
+S	B
+.	I
+aureus	I
+shuttle	O
+vectors	O
+pAW17	O
+and	O
+pBUS1	O
+[	O
+37	O
+]	O
+,	O
+creating	O
+the	O
+complementing	O
+plasmids	O
+pME26	O
+and	O
+pME27	O
+,	O
+respectively	O
+.	O
+
+Plasmids	O
+were	O
+electroporated	O
+into	O
+RN4220	O
+[	O
+38	O
+]	O
+and	O
+then	O
+transduced	O
+into	O
+different	O
+strains	O
+using	O
+phage	O
+80	O
+alpha	O
+.	O
+
+Northern	O
+blot	O
+analysis	O
+
+Strains	O
+were	O
+grown	O
+overnight	O
+in	O
+LB	O
+(	O
+Difco	O
+)	O
+,	O
+diluted	O
+1	O
+:	O
+200	O
+and	O
+grown	O
+for	O
+another	O
+3	O
+h	O
+.	O
+
+This	O
+preculture	O
+was	O
+used	O
+to	O
+inoculate	O
+150	O
+ml	O
+(	O
+1	O
+:	O
+1000	O
+)	O
+of	O
+fresh	O
+prewarmed	O
+LB	O
+.	O
+
+Cells	O
+were	O
+then	O
+grown	O
+to	O
+OD600	O
+nm	O
+0	O
+.	O
+25	O
+or	O
+1	O
+.	O
+0	O
+and	O
+either	O
+left	O
+uninduced	O
+or	O
+induced	O
+with	O
+cefoxitin	O
+4	O
+or	O
+120	O
+mu	O
+g	O
+/	O
+ml	O
+.	O
+
+Cultures	O
+were	O
+sampled	O
+from	O
+both	O
+uninduced	O
+and	O
+induced	O
+cells	O
+at	O
+time	O
+point	O
+0	O
+'	O
+before	O
+induction	O
+and	O
+at	O
+10	O
+'	O
+and	O
+30	O
+'	O
+(	O
+min	O
+)	O
+after	O
+induction	O
+.	O
+
+To	O
+monitor	O
+SA1665	O
+expression	O
+over	O
+growth	O
+,	O
+separate	O
+cultures	O
+were	O
+also	O
+sampled	O
+at	O
+different	O
+growth	O
+stages	O
+corresponding	O
+to	O
+OD600	O
+nm	O
+0	O
+.	O
+25	O
+,	O
+0	O
+.	O
+5	O
+,	O
+1	O
+,	O
+2	O
+,	O
+and	O
+4	O
+.	O
+
+Total	O
+RNA	O
+was	O
+extracted	O
+as	O
+described	O
+by	O
+Cheung	O
+et	O
+al	O
+.	O
+
+[	O
+39	O
+]	O
+.	O
+
+RNA	O
+samples	O
+(	O
+10	O
+mu	O
+g	O
+)	O
+were	O
+separated	O
+in	O
+a	O
+1	O
+.	O
+5	O
+%	O
+agarose	O
+-	O
+20	O
+mM	O
+guanidine	O
+thiocyanate	O
+gel	O
+in	O
+1	O
+x	O
+TBE	O
+running	O
+buffer	O
+[	O
+40	O
+]	O
+,	O
+then	O
+transferred	O
+and	O
+detected	O
+as	O
+described	O
+previously	O
+[	O
+41	O
+]	O
+.	O
+
+Digoxigenin	O
+(	O
+DIG	O
+)	O
+labelled	O
+-	O
+probes	O
+were	O
+amplified	O
+using	O
+the	O
+PCR	O
+DIG	O
+Probe	O
+synthesis	O
+kit	O
+(	O
+Roche	O
+)	O
+.	O
+
+Table	O
+2	O
+contains	O
+the	O
+list	O
+of	O
+primer	O
+pairs	O
+used	O
+for	O
+the	O
+amplification	O
+of	O
+SA1664	O
+,	O
+SA1665	O
+,	O
+SA1666	O
+,	O
+SA1667	O
+,	O
+mecR1	O
+and	O
+mecA	O
+[	O
+42	O
+]	O
+probes	O
+.	O
+
+All	O
+Northern	O
+'	O
+s	O
+were	O
+repeated	O
+at	O
+least	O
+two	O
+times	O
+,	O
+using	O
+independently	O
+isolated	O
+RNA	O
+samples	O
+.	O
+
+Western	O
+blot	O
+analysis	O
+
+Cells	O
+were	O
+cultured	O
+,	O
+as	O
+described	O
+for	O
+Northern	O
+blot	O
+analysis	O
+,	O
+to	O
+OD600	O
+nm	O
+1	O
+.	O
+0	O
+,	O
+then	O
+induced	O
+with	O
+cefoxitin	O
+4	O
+mu	O
+g	O
+/	O
+ml	O
+.	O
+
+Samples	O
+were	O
+collected	O
+at	O
+time	O
+0	O
+(	O
+before	O
+induction	O
+)	O
+,	O
+10	O
+and	O
+30	O
+min	O
+(	O
+after	O
+induction	O
+)	O
+.	O
+
+Cells	O
+were	O
+harvested	O
+by	O
+centrifugation	O
+,	O
+resuspended	O
+in	O
+PBS	O
+pH	O
+7	O
+.	O
+4	O
+containing	O
+DNase	O
+,	O
+lysostaphin	O
+and	O
+lysozyme	O
+(	O
+150	O
+mu	O
+g	O
+/	O
+ml	O
+of	O
+each	O
+)	O
+and	O
+incubated	O
+for	O
+1	O
+h	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+Suspensions	O
+were	O
+then	O
+sonicated	O
+and	O
+protein	O
+aliquots	O
+(	O
+15	O
+mu	O
+g	O
+)	O
+were	O
+separated	O
+on	O
+7	O
+.	O
+5	O
+%	O
+SDS	O
+-	O
+polyacrylamide	O
+gels	O
+,	O
+blotted	O
+onto	O
+nitrocellulose	O
+membranes	O
+(	O
+Hybond	O
+)	O
+and	O
+stained	O
+with	O
+Ponceau	O
+to	O
+confirm	O
+equal	O
+protein	O
+loading	O
+.	O
+
+PBP2a	O
+detection	O
+was	O
+performed	O
+using	O
+monoclonal	O
+PBP2a	O
+antibody	O
+(	O
+1	O
+:	O
+20000	O
+)	O
+from	O
+the	O
+MRSA	B
+-	O
+screen	O
+kit	O
+(	O
+Denka	O
+Seiken	O
+)	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+ME	O
+carried	O
+out	O
+molecular	O
+genetic	O
+and	O
+microbiological	O
+studies	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+BB	O
+participated	O
+in	O
+the	O
+design	O
+of	O
+the	O
+study	O
+and	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+.	O
+
+NM	O
+participated	O
+in	O
+the	O
+design	O
+and	O
+coordination	O
+of	O
+the	O
+study	O
+,	O
+carried	O
+out	O
+molecular	O
+biological	O
+studies	O
+and	O
+helped	O
+to	O
+draft	O
+the	O
+manuscript	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Organization	O
+and	O
+structure	O
+of	O
+the	O
+mouse	B
+interleukin	O
+-	O
+2	O
+gene	O
+.	O
+
+Abstract	O
+
+We	O
+have	O
+cloned	O
+a	O
+chromosomal	O
+DNA	O
+segment	O
+which	O
+covers	O
+the	O
+entire	O
+sequence	O
+for	O
+the	O
+murine	B
+interleukin	O
+-	O
+2	O
+gene	O
+and	O
+analysed	O
+the	O
+structure	O
+of	O
+the	O
+gene	O
+.	O
+
+The	O
+coding	O
+regions	O
+are	O
+separated	O
+into	O
+four	O
+blocks	O
+by	O
+three	O
+introns	O
+each	O
+of	O
+which	O
+is	O
+located	O
+similarly	O
+to	O
+the	O
+corresponding	O
+human	B
+gene	O
+.	O
+
+The	O
+exon	O
+sequences	O
+can	O
+be	O
+aligned	O
+perfectly	O
+with	O
+the	O
+previously	O
+cloned	O
+cDNA	O
+sequence	O
+.	O
+
+Of	O
+particular	O
+interests	O
+is	O
+the	O
+presence	O
+of	O
+sequences	O
+within	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+which	O
+are	O
+highly	O
+conserved	O
+between	O
+mouse	B
+and	O
+man	B
+.	O
+
+The	O
+conserved	O
+region	O
+which	O
+spans	O
+more	O
+than	O
+400	O
+base	O
+pairs	O
+may	O
+play	O
+a	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+IL	O
+-	O
+2	O
+gene	O
+expression	O
+.	O
+Images	O
+
+Volume	O
+12	O
+Number	O
+24	O
+1984	O
+Nucleic	O
+Acids	O
+Research	O
+
+Organization	O
+and	O
+structure	O
+of	O
+the	O
+mouse	B
+interleukin	O
+-	O
+2	O
+gene	O
+
+Akira	O
+Fuse	O
+*	O
+,	O
+Takashi	O
+Fujita	O
+,	O
+Hidetaro	O
+Yasumitsu	O
+,	O
+Nobukazu	O
+Kashima	O
++	O
+,	O
+Katsushige	O
+Hasegawa	O
+and	O
+Tadatsugu	O
+Taniguchi	O
+?	O
+
+Department	O
+of	O
+Biochemistry	O
+,	O
+Cancer	O
+Institute	O
+,	O
+Japanese	O
+Foundation	O
+for	O
+Cancer	O
+Research	O
+,	O
+Toshimaku	O
+,	O
+Tokyo	O
+170	O
+and	O
+Institute	O
+for	O
+Molecular	O
+and	O
+Cellular	O
+Biology	O
+,	O
+Osaka	O
+University	O
+,	O
+Suita	O
+-	O
+shi	O
+,	O
+Osaka	O
+565	O
+,	O
+Japan	O
+
+Received	O
+10	O
+October	O
+1984	O
+;	O
+Revised	O
+and	O
+Accepted	O
+20	O
+November	O
+1984	O
+
+ABSTRACT	O
+
+We	O
+have	O
+cloned	O
+a	O
+chromosomal	O
+DNA	O
+segment	O
+which	O
+covers	O
+the	O
+entire	O
+sequence	O
+for	O
+the	O
+murine	B
+interleukin	O
+-	O
+2	O
+gene	O
+and	O
+analysed	O
+the	O
+structure	O
+of	O
+the	O
+gene	O
+.	O
+
+The	O
+coding	O
+regions	O
+are	O
+separated	O
+into	O
+four	O
+blocks	O
+by	O
+three	O
+introns	O
+each	O
+of	O
+which	O
+is	O
+located	O
+similarly	O
+to	O
+the	O
+corresponding	O
+human	B
+gene	O
+.	O
+
+The	O
+exon	O
+sequences	O
+can	O
+be	O
+aligned	O
+perfectly	O
+with	O
+the	O
+previously	O
+cloned	O
+cDNA	O
+sequence	O
+.	O
+
+Of	O
+particular	O
+interests	O
+is	O
+the	O
+presence	O
+of	O
+sequences	O
+within	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+which	O
+are	O
+highly	O
+conserved	O
+between	O
+mouse	B
+and	O
+man	B
+.	O
+
+The	O
+conserved	O
+region	O
+which	O
+spans	O
+more	O
+than	O
+400	O
+base	O
+pairs	O
+may	O
+play	O
+a	O
+role	O
+in	O
+the	O
+regulation	O
+of	O
+IL	O
+-	O
+2	O
+gene	O
+expression	O
+.	O
+
+INTRODUCTION	O
+
+Interleukin	O
+-	O
+2	O
+(	O
+IL	O
+-	O
+2	O
+)	O
+is	O
+a	O
+lymphokine	O
+produced	O
+by	O
+T	O
+cells	O
+upon	O
+antigenic	O
+or	O
+mitogenic	O
+stimulation	O
+and	O
+is	O
+required	O
+for	O
+the	O
+proliferation	O
+of	O
+T	O
+cells	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+Several	O
+other	O
+biological	O
+activities	O
+of	O
+IL	O
+-	O
+2	O
+which	O
+appear	O
+to	O
+be	O
+crucial	O
+in	O
+the	O
+immune	O
+regulation	O
+have	O
+also	O
+been	O
+reported	O
+(	O
+3	O
+,	O
+4	O
+.	O
+5	O
+.	O
+6	O
+.	O
+7	O
+.	O
+)	O
+.	O
+
+We	O
+previously	O
+reported	O
+isolation	O
+and	O
+sequence	O
+analysis	O
+of	O
+the	O
+cDNA	O
+for	O
+human	B
+IL	O
+-	O
+2	O
+(	O
+8	O
+)	O
+,	O
+as	O
+well	O
+as	O
+the	O
+chromosomal	O
+gene	O
+(	O
+9	O
+)	O
+.	O
+
+More	O
+recently	O
+,	O
+we	O
+have	O
+isolated	O
+a	O
+cDNA	O
+which	O
+encodes	O
+murine	B
+IL	O
+-	O
+2	O
+(	O
+Kashima	O
+et	O
+al	O
+.	O
+,	O
+submitted	O
+for	O
+publication	O
+)	O
+.	O
+
+The	O
+cDNA	O
+contains	O
+a	O
+unique	O
+tandem	O
+repeat	O
+of	O
+CAG	O
+sequence	O
+which	O
+would	O
+encode	O
+12	O
+consecutive	O
+glutamine	O
+residues	O
+in	O
+the	O
+active	O
+IL	O
+-	O
+2	O
+molecule	O
+.	O
+
+In	O
+order	O
+to	O
+study	O
+the	O
+structure	O
+of	O
+the	O
+murine	B
+IL	O
+-	O
+2	O
+chromosomal	O
+gene	O
+and	O
+its	O
+controlling	O
+region	O
+,	O
+we	O
+isolated	O
+and	O
+analysed	O
+a	O
+A	O
+phage	O
+clone	O
+containing	O
+the	O
+gene	O
+and	O
+its	O
+flanking	O
+sequences	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+
+Southern	O
+blotting	O
+of	O
+total	O
+mouse	B
+DNA	O
+
+Mouse	B
+chromosomal	O
+DNA	O
+was	O
+extracted	O
+from	O
+liver	O
+of	O
+BALB	O
+/	O
+c6	O
+
+?	O
+I	O
+R	O
+L	O
+Press	O
+Limited	O
+,	O
+Oxford	O
+,	O
+England	O
+.	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Volume	O
+12	O
+Number	O
+24	O
+1984	O
+
+9323	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+mouse	B
+as	O
+described	O
+before	O
+(	O
+10	O
+)	O
+.	O
+
+High	O
+molecular	O
+genomic	O
+DNA	O
+was	O
+digested	O
+with	O
+various	O
+restriction	O
+enzymes	O
+and	O
+electrophoresed	O
+on	O
+0	O
+.	O
+8	O
+%	O
+agarose	O
+gel	O
+.	O
+
+Blotting	O
+analysis	O
+of	O
+DNA	O
+was	O
+carried	O
+out	O
+by	O
+the	O
+method	O
+of	O
+Southern	O
+(	O
+11	O
+)	O
+.	O
+
+Hybridization	O
+was	O
+carried	O
+out	O
+as	O
+described	O
+previously	O
+and	O
+filters	O
+were	O
+washed	O
+either	O
+in	O
+3	O
+x	O
+SSC	O
+at	O
+650C	O
+(	O
+lower	O
+stringent	O
+condition	O
+)	O
+or	O
+in	O
+0	O
+.	O
+1	O
+x	O
+SSC	O
+at	O
+650C	O
+(	O
+higher	O
+stringent	O
+condition	O
+)	O
+.	O
+
+Screening	O
+of	O
+genomic	O
+DNA	O
+library	O
+
+A	O
+bacteriophage	O
+XCharon	O
+4A	O
+/	O
+mouse	B
+genomic	O
+DNA	O
+library	O
+prepared	O
+with	O
+partial	O
+EcoRI	O
+digests	O
+of	O
+mouse	B
+DNA	O
+from	O
+MPC	O
+11	O
+plasmacytoma	O
+cells	O
+was	O
+kindly	O
+provided	O
+by	O
+Dr	O
+.	O
+T	O
+.	O
+
+Honjo	O
+.	O
+
+Mouse	B
+IL	O
+-	O
+2	O
+-	O
+specific	O
+clones	O
+were	O
+screened	O
+by	O
+the	O
+method	O
+of	O
+Benton	O
+and	O
+Davis	O
+(	O
+12	O
+)	O
+,	O
+using	O
+700	O
+bp	O
+PstI	O
+-	O
+AccI	O
+fragment	O
+of	O
+a	O
+cDNA	O
+clone	O
+,	O
+pMIL2	O
+-	O
+45	O
+as	O
+the	O
+probe	O
+(	O
+Kashima	O
+et	O
+al	O
+.	O
+,	O
+submitted	O
+for	O
+publication	O
+)	O
+.	O
+
+Hybridization	O
+was	O
+performed	O
+as	O
+described	O
+previously	O
+(	O
+13	O
+)	O
+.	O
+
+Positive	O
+clones	O
+were	O
+rescreened	O
+at	O
+least	O
+twice	O
+.	O
+
+Subcloninq	O
+and	O
+sequencing	O
+of	O
+the	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+
+Two	O
+EcoRI	O
+fragments	O
+of	O
+3	O
+.	O
+3	O
+Kbp	O
+and	O
+2	O
+.	O
+8	O
+Kbp	O
+from	O
+the	O
+positive	O
+recombinant	O
+X	O
+phage	O
+were	O
+subcloned	O
+into	O
+EcoRI	O
+site	O
+of	O
+plasmid	O
+pBR322	O
+.	O
+
+DNA	O
+segments	O
+derived	O
+from	O
+subcloned	O
+3	O
+.	O
+3	O
+Kbp	O
+and	O
+2	O
+.	O
+8	O
+Kbp	O
+fragments	O
+were	O
+labelled	O
+at	O
+either	O
+3	O
+'	O
+end	O
+or	O
+5	O
+'	O
+end	O
+,	O
+and	O
+subjected	O
+to	O
+sequence	O
+analysis	O
+by	O
+the	O
+chemical	O
+degradation	O
+method	O
+(	O
+14	O
+)	O
+.	O
+
+The	O
+0	O
+.	O
+8	O
+Kbp	O
+EcoRI	O
+fragment	O
+from	O
+the	O
+same	O
+X	O
+phage	O
+clone	O
+was	O
+directly	O
+subjected	O
+to	O
+sequence	O
+analysis	O
+by	O
+the	O
+dideoxy	O
+chain	O
+termination	O
+method	O
+(	O
+15	O
+)	O
+.	O
+
+RESULTS	O
+
+Total	O
+DNA	O
+blotting	O
+analysis	O
+
+In	O
+order	O
+to	O
+study	O
+structural	O
+organization	O
+of	O
+the	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+,	O
+we	O
+first	O
+subjected	O
+total	O
+mouse	B
+DNA	O
+to	O
+the	O
+blotting	O
+analysis	O
+by	O
+using	O
+various	O
+probes	O
+specific	O
+for	O
+IL	O
+-	O
+2	O
+gene	O
+.	O
+
+When	O
+mouse	B
+DNA	O
+was	O
+digested	O
+with	O
+various	O
+restriction	O
+endonucleases	O
+and	O
+then	O
+probed	O
+with	O
+a	O
+7	O
+kb	O
+human	B
+chromosomal	O
+DNA	O
+segment	O
+which	O
+contains	O
+the	O
+human	B
+IL	O
+-	O
+2	O
+gene	O
+and	O
+its	O
+flanking	O
+region	O
+(	O
+Fig	O
+.	O
+1	O
+lane	O
+1	O
+-	O
+8	O
+,	O
+ref	O
+.	O
+9	O
+.	O
+)	O
+,	O
+single	O
+positive	O
+band	O
+appeared	O
+at	O
+lower	O
+but	O
+not	O
+at	O
+higher	O
+stringent	O
+condition	O
+for	O
+washing	O
+the	O
+filters	O
+(	O
+see	O
+Figure	O
+legend	O
+)	O
+.	O
+
+Additional	O
+bands	O
+corresponding	O
+to	O
+those	O
+observed	O
+by	O
+using	O
+mouse	B
+IL	O
+-	O
+2	O
+cDNA	O
+probes	O
+(	O
+lane	O
+13	O
+-	O
+17	O
+)	O
+also	O
+appeared	O
+by	O
+longer	O
+
+9324	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+M	O
+1	O
+2	O
+3	O
+4	O
+M	O
+5	O
+6	O
+7	O
+8	O
+M	O
+9	O
+101112	O
+M	O
+13	O
+141516	O
+17	O
+
+a	O
+~	O
+~	O
+3	O
+.	O
+.	O
+
+I	O
+pMIL2	O
+-	O
+45	O
+SacI	O
+Acc	O
+I	O
+
+CZI	O
+~	O
+~	O
+1	O
+1t	O
+L2	O
+-	O
+20	O
+
+Acc	O
+I	O
+
+1	O
+00	O
+tp	O
+lX	O
+i	O
+
+Fig	O
+.	O
+
+1	O
+.	O
+
+Blot	O
+hybridization	O
+analysis	O
+of	O
+mouse	B
+chromosomal	O
+DNA	O
+.	O
+
+High	O
+molecular	O
+DNA	O
+prepared	O
+from	O
+Liver	O
+BALB	O
+/	O
+C6	O
+mouse	B
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+digested	O
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+restriction	O
+endonucleases	O
+(	O
+BamHI	O
+for	O
+lanes	O
+1	O
+,	O
+5	O
+,	O
+9	O
+,	O
+13	O
+;	O
+EcoRI	O
+for	O
+lanes	O
+2	O
+,	O
+6	O
+,	O
+10	O
+,	O
+14	O
+,	O
+17	O
+;	O
+HindIII	O
+for	O
+lanes	O
+3	O
+,	O
+7	O
+,	O
+11	O
+,	O
+15	O
+;	O
+XbaI	O
+for	O
+lanes	O
+4	O
+,	O
+8	O
+,	O
+12	O
+,	O
+16	O
+)	O
+.	O
+
+The	O
+resulting	O
+digests	O
+were	O
+fractionated	O
+on	O
+0	O
+.	O
+8	O
+%	O
+agarose	O
+gel	O
+and	O
+transferred	O
+to	O
+a	O
+nitrocellulose	O
+filter	O
+.	O
+
+Filters	O
+were	O
+hybridized	O
+by	O
+the	O
+published	O
+procedure	O
+(	O
+13	O
+)	O
+either	O
+with	O
+the	O
+nick	O
+-	O
+translated	O
+chromosomal	O
+DNA	O
+containing	O
+human	B
+IL	O
+-	O
+2	O
+gene	O
+and	O
+its	O
+flanking	O
+region	O
+(	O
+total	O
+length	O
+,	O
+7	O
+.	O
+0	O
+kb	O
+,	O
+ref	O
+.	O
+9	O
+)	O
+(	O
+lane	O
+1	O
+-	O
+8	O
+)	O
+or	O
+with	O
+the	O
+nick	O
+-	O
+translated	O
+cDNA	O
+for	O
+mouse	B
+IL	O
+-	O
+2	O
+(	O
+see	O
+figure	O
+)	O
+.	O
+
+Filters	O
+were	O
+then	O
+washed	O
+either	O
+in	O
+3	O
+x	O
+SSC	O
+at	O
+65	O
+%	O
+(	O
+lower	O
+stringent	O
+condition	O
+)	O
+(	O
+lane	O
+1	O
+-	O
+4	O
+,	O
+9	O
+-	O
+12	O
+)	O
+or	O
+0	O
+.	O
+1	O
+x	O
+SSC	O
+at	O
+65	O
+OC	O
+(	O
+higher	O
+stringent	O
+condition	O
+)	O
+(	O
+lane	O
+5	O
+-	O
+8	O
+,	O
+13	O
+-	O
+17	O
+)	O
+.	O
+
+Lane	O
+M	O
+each	O
+contains	O
+7	O
+size	O
+markers	O
+with	O
+their	O
+size	O
+being	O
+23	O
+.	O
+7	O
+kb	O
+,	O
+9	O
+.	O
+5	O
+kb	O
+,	O
+6	O
+.	O
+7	O
+kb	O
+,	O
+4	O
+.	O
+3	O
+kb	O
+,	O
+2	O
+.	O
+3	O
+kb	O
+,	O
+2	O
+.	O
+0	O
+kb	O
+and	O
+0	O
+.	O
+6	O
+kb	O
+,	O
+respectively	O
+.	O
+
+Brief	O
+restriction	O
+endonuclease	O
+cleavage	O
+map	O
+for	O
+the	O
+mouse	B
+IL	O
+-	O
+2	O
+cDNAs	O
+is	O
+presented	O
+in	O
+the	O
+lower	O
+part	O
+of	O
+the	O
+figure	O
+.	O
+
+exposure	O
+of	O
+the	O
+film	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+Those	O
+results	O
+suggest	O
+the	O
+presence	O
+of	O
+highly	O
+conserved	O
+sequences	O
+between	O
+human	B
+and	O
+mouse	B
+DNA	O
+either	O
+in	O
+the	O
+flanking	O
+regions	O
+or	O
+in	O
+the	O
+introns	O
+of	O
+the	O
+IL	O
+-	O
+2	O
+gene	O
+,	O
+since	O
+the	O
+coding	O
+regions	O
+apparently	O
+show	O
+lower	O
+degree	O
+of	O
+sequence	O
+homology	O
+as	O
+evidenced	O
+in	O
+this	O
+series	O
+of	O
+blotting	O
+analysis	O
+(	O
+see	O
+below	O
+)	O
+.	O
+
+When	O
+the	O
+PstI	O
+insert	O
+of	O
+a	O
+mouse	B
+IL	O
+-	O
+2	O
+cDNA	O
+clone	O
+,	O
+pMIL2	O
+-	O
+20	O
+,	O
+was	O
+used	O
+as	O
+the	O
+probe	O
+,	O
+a	O
+simple	O
+pattern	O
+was	O
+
+9325	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+obtained	O
+at	O
+higher	O
+stringent	O
+condition	O
+(	O
+lane	O
+13	O
+-	O
+17	O
+)	O
+.	O
+
+While	O
+the	O
+EcoRI	O
+-	O
+digested	O
+DNA	O
+gave	O
+rise	O
+to	O
+two	O
+positive	O
+bands	O
+(	O
+2	O
+.	O
+8	O
+kb	O
+and	O
+0	O
+.	O
+8	O
+kb	O
+)	O
+(	O
+Fig	O
+.	O
+1	O
+,	O
+lane	O
+14	O
+)	O
+by	O
+this	O
+analysis	O
+,	O
+one	O
+additional	O
+band	O
+of	O
+3	O
+.	O
+3	O
+kb	O
+also	O
+appeared	O
+when	O
+the	O
+same	O
+DNA	O
+was	O
+probed	O
+with	O
+a	O
+longer	O
+cDNA	O
+insert	O
+from	O
+another	O
+clone	O
+,	O
+pMIL2	O
+-	O
+45	O
+(	O
+Fig	O
+.	O
+1	O
+,	O
+lane	O
+17	O
+)	O
+.	O
+
+The	O
+3	O
+.	O
+3	O
+kb	O
+band	O
+was	O
+similar	O
+in	O
+its	O
+size	O
+with	O
+the	O
+positive	O
+band	O
+which	O
+became	O
+detectable	O
+by	O
+probing	O
+the	O
+same	O
+DNA	O
+with	O
+the	O
+7	O
+.	O
+0	O
+kb	O
+human	B
+DNA	O
+probe	O
+(	O
+Fig	O
+.	O
+1	O
+,	O
+lane	O
+2	O
+)	O
+.	O
+
+Since	O
+this	O
+band	O
+appeared	O
+with	O
+the	O
+cDNA	O
+probe	O
+extending	O
+further	O
+upstream	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+the	O
+5	O
+'	O
+region	O
+of	O
+the	O
+gene	O
+is	O
+located	O
+within	O
+this	O
+DNA	O
+segment	O
+(	O
+see	O
+below	O
+)	O
+.	O
+
+Indeed	O
+,	O
+this	O
+3	O
+.	O
+3	O
+kb	O
+band	O
+did	O
+not	O
+appear	O
+even	O
+after	O
+longer	O
+exposure	O
+of	O
+lane	O
+14	O
+(	O
+result	O
+not	O
+shown	O
+)	O
+.	O
+
+BamHI	O
+digest	O
+of	O
+the	O
+mouse	B
+DNA	O
+(	O
+Fig	O
+.	O
+1	O
+,	O
+lane	O
+1	O
+,	O
+13	O
+)	O
+constantly	O
+gave	O
+a	O
+very	O
+faint	O
+signal	O
+which	O
+would	O
+correspond	O
+to	O
+a	O
+DNA	O
+larger	O
+than	O
+15	O
+kb	O
+.	O
+
+Taken	O
+together	O
+,	O
+the	O
+results	O
+suggested	O
+the	O
+presence	O
+of	O
+a	O
+single	O
+copy	O
+gene	O
+for	O
+murine	B
+IL	O
+-	O
+2	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+appearance	O
+of	O
+the	O
+multiple	O
+positive	O
+bands	O
+at	O
+lower	O
+stringent	O
+washing	O
+condition	O
+(	O
+lane	O
+9	O
+-	O
+12	O
+)	O
+indicates	O
+the	O
+presence	O
+of	O
+IL	O
+-	O
+2	O
+related	O
+sequences	O
+within	O
+the	O
+mouse	B
+genome	O
+.	O
+
+Screening	O
+of	O
+recombinant	O
+phaqe	O
+libraries	O
+
+We	O
+next	O
+screened	O
+a	O
+gene	O
+library	O
+from	O
+partial	O
+EcoRIdigested	O
+DNA	O
+from	O
+MPC	O
+11	O
+cells	O
+and	O
+by	O
+using	O
+0	O
+.	O
+8	O
+Kbp	O
+SacI	O
+-	O
+AccI	O
+cDNA	O
+fragment	O
+as	O
+the	O
+probe	O
+and	O
+isolated	O
+14	O
+positive	O
+clones	O
+containing	O
+sequences	O
+specific	O
+to	O
+the	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+.	O
+
+Three	O
+of	O
+the	O
+clones	O
+analysed	O
+all	O
+contained	O
+three	O
+EcoRI	O
+fragments	O
+whose	O
+size	O
+is	O
+in	O
+agreement	O
+with	O
+the	O
+result	O
+of	O
+blotting	O
+analysis	O
+of	O
+the	O
+chromosomal	O
+DNA	O
+as	O
+shown	O
+in	O
+Fig	O
+.	O
+
+1	O
+(	O
+lane	O
+17	O
+)	O
+.	O
+
+One	O
+of	O
+these	O
+is	O
+designated	O
+MIL	O
+-	O
+2G70	O
+.	O
+
+Nucleotide	O
+sequence	O
+analysis	O
+
+Two	O
+DNA	O
+fragments	O
+of	O
+3	O
+.	O
+3	O
+Kbp	O
+and	O
+2	O
+.	O
+8	O
+Kbp	O
+were	O
+excised	O
+from	O
+the	O
+phage	O
+clone	O
+MIL	O
+-	O
+2G70	O
+by	O
+EcoRI	O
+digestion	O
+and	O
+they	O
+were	O
+subcloned	O
+into	O
+pBR322	O
+.	O
+
+DNA	O
+sequences	O
+were	O
+determined	O
+for	O
+selected	O
+regions	O
+of	O
+both	O
+inserts	O
+and	O
+compared	O
+to	O
+the	O
+known	O
+cDNA	O
+sequences	O
+(	O
+Kashima	O
+et	O
+al	O
+.	O
+,	O
+submitted	O
+for	O
+publication	O
+)	O
+.	O
+
+The	O
+strategy	O
+used	O
+for	O
+sequence	O
+analysis	O
+of	O
+the	O
+genomic	O
+DNA	O
+is	O
+presented	O
+in	O
+Fig	O
+.	O
+
+2	O
+.	O
+
+Comparison	O
+of	O
+the	O
+mouse	B
+genomic	O
+IL	O
+-	O
+2	O
+sequence	O
+with	O
+mouse	B
+IL	O
+-	O
+2	O
+cDNA	O
+sequence	O
+revealed	O
+that	O
+,	O
+like	O
+the	O
+human	B
+gene	O
+,	O
+the	O
+gene	O
+is	O
+divided	O
+into	O
+four	O
+exons	O
+.	O
+
+A	O
+putative	O
+
+9326	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+E	O
+E	O
+E	O
+E	O
+E	O
+
+500bp	O
+s	O
+7S	O
+P	O
+HBH	O
+H	O
+\	O
+A	O
+
+200	O
+bp	O
+*	O
+,	O
+-	O
+4	O
+
+I	O
+4	O
+-	O
+4	O
+-	O
+-	O
+-	O
+-	O
+*	O
+*	O
+-	O
+-	O
+-	O
+4	O
+
+Fig	O
+.	O
+
+2	O
+.	O
+
+Restriction	O
+map	O
+and	O
+sequencing	O
+strategy	O
+of	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+.	O
+
+Horizontal	O
+lines	O
+indicate	O
+the	O
+length	O
+of	O
+mouse	B
+DNA	O
+inserted	O
+into	O
+the	O
+X	O
+phage	O
+Charon	O
+4A	O
+or	O
+plasmid	O
+subclones	O
+.	O
+
+Filled	O
+blocks	O
+,	O
+dashed	O
+blocks	O
+and	O
+open	O
+blocks	O
+indicate	O
+protein	O
+coding	O
+regions	O
+,	O
+untranslated	O
+regions	O
+and	O
+introns	O
+,	O
+respectively	O
+.	O
+
+Horizontal	O
+arrows	O
+indicate	O
+the	O
+direction	O
+and	O
+extent	O
+of	O
+sequence	O
+determination	O
+without	O
+ambiguity	O
+.	O
+
+Dashed	O
+arrows	O
+:	O
+determination	O
+was	O
+done	O
+by	O
+the	O
+chain	O
+termination	O
+method	O
+(	O
+15	O
+)	O
+after	O
+subcloning	O
+the	O
+0	O
+.	O
+8	O
+kb	O
+fragment	O
+into	O
+M13	O
+.	O
+
+Rest	O
+of	O
+the	O
+sequence	O
+determination	O
+was	O
+carried	O
+out	O
+by	O
+the	O
+method	O
+of	O
+Maxam	O
+and	O
+Gilbert	O
+(	O
+14	O
+)	O
+.	O
+
+A	O
+AccI	O
+site	O
+,	O
+B	O
+;	O
+BamHI	O
+site	O
+,	O
+E	O
+;	O
+EcoRI	O
+site	O
+,	O
+H	O
+;	O
+HindIII	O
+site	O
+,	O
+P	O
+;	O
+PstI	O
+site	O
+,	O
+S	O
+;	O
+SacI	O
+site	O
+.	O
+
+capping	O
+site	O
+or	O
+the	O
+transcription	O
+initiation	O
+site	O
+was	O
+located	O
+32	O
+bp	O
+downstream	O
+from	O
+a	O
+TATAAA	O
+consensus	O
+promotor	O
+sequence	O
+(	O
+Fig	O
+.	O
+
+3	O
+)	O
+.	O
+The	O
+first	O
+ATG	O
+triplet	O
+was	O
+located	O
+79	O
+bp	O
+downstream	O
+from	O
+the	O
+TATA	O
+box	O
+.	O
+
+As	O
+seen	O
+also	O
+in	O
+the	O
+murine	B
+IL	O
+-	O
+2	O
+cDNA	O
+,	O
+there	O
+is	O
+an	O
+unusual	O
+repeat	O
+of	O
+CAG	O
+triplet	O
+coding	O
+for	O
+12	O
+glutamine	O
+residues	O
+in	O
+a	O
+row	O
+in	O
+the	O
+first	O
+exon	O
+.	O
+
+The	O
+second	O
+exon	O
+(	O
+60	O
+bp	O
+)	O
+is	O
+separated	O
+from	O
+the	O
+first	O
+exon	O
+by	O
+a	O
+short	O
+intron	O
+consisting	O
+of	O
+97	O
+bp	O
+.	O
+
+The	O
+second	O
+,	O
+the	O
+third	O
+and	O
+the	O
+fourth	O
+exons	O
+are	O
+interrupted	O
+by	O
+longer	O
+introns	O
+whose	O
+size	O
+is	O
+about	O
+2	O
+.	O
+3	O
+Kbp	O
+and	O
+1	O
+.	O
+6	O
+Kbp	O
+,	O
+respectively	O
+.	O
+
+As	O
+far	O
+as	O
+the	O
+available	O
+sequence	O
+data	O
+are	O
+concerned	O
+,	O
+it	O
+seems	O
+that	O
+,	O
+despite	O
+their	O
+identical	O
+location	O
+,	O
+intron	O
+sequences	O
+are	O
+distinctly	O
+dissimilar	O
+except	O
+for	O
+the	O
+junction	O
+regions	O
+between	O
+the	O
+human	B
+and	O
+mouse	B
+IL	O
+-	O
+2	O
+genes	O
+.	O
+
+There	O
+are	O
+two	O
+potential	O
+poly	O
+(	O
+A	O
+)	O
+addition	O
+signals	O
+within	O
+the	O
+mouse	B
+gene	O
+(	O
+nucleotide	O
+positions	O
+793	O
+-	O
+798	O
+and	O
+924	O
+-	O
+929	O
+in	O
+Fig	O
+.	O
+3	O
+)	O
+and	O
+,	O
+based	O
+on	O
+our	O
+sequence	O
+data	O
+for	O
+various	O
+cDNA	O
+clones	O
+,	O
+both	O
+signals	O
+seem	O
+to	O
+function	O
+and	O
+give	O
+rise	O
+to	O
+heterogeneous	O
+termini	O
+of	O
+the	O
+mRNA	O
+in	O
+the	O
+LBRM	O
+-	O
+33	O
+cells	O
+(	O
+16	O
+)	O
+.	O
+
+We	O
+have	O
+also	O
+determined	O
+the	O
+sequence	O
+of	O
+about	O
+500	O
+bp	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+,	O
+since	O
+(	O
+i	O
+)	O
+promoter	O
+/	O
+regulatory	O
+sequences	O
+are	O
+located	O
+in	O
+this	O
+region	O
+in	O
+many	O
+other	O
+genes	O
+of	O
+eukaryotes	O
+and	O
+(	O
+ii	O
+)	O
+this	O
+region	O
+appeared	O
+to	O
+contain	O
+sequences	O
+which	O
+show	O
+strongest	O
+cross	O
+-	O
+hybridization	O
+between	O
+human	B
+and	O
+mouse	B
+DNA	O
+around	O
+the	O
+IL	O
+-	O
+2	O
+gene	O
+(	O
+Fig	O
+.	O
+1	O
+)	O
+.	O
+
+Comparison	O
+of	O
+the	O
+nucleotide	O
+sequences	O
+for	O
+the	O
+5	O
+'	O
+flanking	O
+region	O
+
+9327	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+-	O
+4	O
+.	O
+0	O
+
+TAGGAGGTAAACCATCTCGA	O
+-	O
+400	O
+-	O
+350	O
+
+GATTTATTCTTTTCATCTAT	O
+
+-	O
+300	O
+-	O
+250	O
+
+CATGAGTTACTTTTGTGTCT	O
+
+-	O
+200	O
+-	O
+150	O
+
+TGGGCTAACCCGACCAAGAG	O
+
+-	O
+100	O
+-	O
+50	O
+
+AAACAAAGGTAATACTTTCT	O
+CAGCATTAACAGTATAAATT	O
+TCACCCTTGCTAATCACTCC	O
+
+50	O
+100	O
+
+ATG	O
+TAC	O
+AGC	O
+ATG	O
+CAG	O
+CTC	O
+GCA	O
+TCC	O
+TGT	O
+GTC	O
+ACA	O
+TTG	O
+ACA	O
+CTT	O
+GTG	O
+CTC	O
+CTT	O
+GTC	O
+AAC	O
+AGC	O
+GCA	O
+CCC	O
+ACT	O
+Met	O
+Tyr	O
+Ser	O
+Met	O
+Gln	O
+Leu	O
+Ala	O
+Ser	O
+Cys	O
+Val	O
+Thr	O
+Leu	O
+Thr	O
+Leu	O
+Val	O
+Leu	O
+Leu	O
+Val	O
+Asn	O
+Ser	O
+Ala	O
+Pro	O
+Thr	O
+
+150	O
+
+TCA	O
+AGC	O
+TCC	O
+ACT	O
+TCA	O
+AGC	O
+TCT	O
+ACA	O
+GCG	O
+GAA	O
+GCA	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+CAG	O
+Ser	O
+Ser	O
+Ser	O
+Thr	O
+Ser	O
+Ser	O
+Ser	O
+Thr	O
+Ala	O
+Glu	O
+Ala	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+Gln	O
+
+200	O
+
+CAC	O
+CTG	O
+GAG	O
+CAG	O
+CTG	O
+TTG	O
+ATG	O
+GAC	O
+CTA	O
+CAG	O
+GAG	O
+CTC	O
+CTG	O
+AGC	O
+AGG	O
+ATG	O
+GAG	O
+GTAAGTGCACAGCCATCCCA	O
+His	O
+Leu	O
+Glu	O
+Gln	O
+Leu	O
+Leu	O
+Met	O
+Asp	O
+Leu	O
+Gln	O
+Glu	O
+Leu	O
+Leu	O
+Ser	O
+Arg	O
+Met	O
+Glu	O
+
+TATAGGCAATACCTTTAGCT	O
+AAT	O
+TAC	O
+AGG	O
+AAC	O
+
+lAsn	O
+Tyr	O
+Arg	O
+Asn	O
+250	O
+
+CTG	O
+AAA	O
+CTC	O
+CCC	O
+AGG	O
+ATG	O
+CTC	O
+ACC	O
+TTC	O
+AAA	O
+TTT	O
+TAC	O
+TTG	O
+CCC	O
+AAG	O
+CAG	O
+GTGAGTGAGTTTCTGTTTAA	O
+Leu	O
+Lys	O
+Leu	O
+Pro	O
+Arg	O
+Met	O
+Leu	O
+Thr	O
+Phe	O
+Lys	O
+Phe	O
+Tyr	O
+Leu	O
+Pro	O
+Lys	O
+Gln	O
+
+TCTAATG	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+_	O
+_	O
+
+?	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+_	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+2000	O
+bp	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+?	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+AATGTGAACCTTGTAGTTTC	O
+TATGCATTGGTAGAGAAACA	O
+TGGTTGTGAGCTCTTGCTCT	O
+CCTTCTCTTGATTAGAGAGA	O
+
+300	O
+350	O
+
+GCC	O
+ACA	O
+GAA	O
+TTG	O
+AAA	O
+GAT	O
+CTT	O
+CAG	O
+TGC	O
+CTA	O
+GAA	O
+GAT	O
+GAA	O
+CTT	O
+GGA	O
+CCT	O
+CTG	O
+CGG	O
+CAT	O
+GTT	O
+CTG	O
+GAT	O
+TTG	O
+Ala	O
+Thr	O
+Glu	O
+Leu	O
+Lys	O
+Asp	O
+Leu	O
+Gln	O
+Cys	O
+Leu	O
+Glu	O
+Asp	O
+Glu	O
+Leu	O
+Gly	O
+Pro	O
+Leu	O
+Arg	O
+His	O
+Val	O
+Leu	O
+Asp	O
+Leu	O
+
+490	O
+
+ACT	O
+CAA	O
+AGC	O
+AAA	O
+AGC	O
+TTT	O
+CAA	O
+TTG	O
+GAA	O
+GAT	O
+GCT	O
+GAG	O
+AAT	O
+TTC	O
+ATC	O
+AGC	O
+AAT	O
+ATC	O
+AGA	O
+GTA	O
+ACT	O
+GTT	O
+GTA	O
+Thr	O
+Gln	O
+Ser	O
+Lys	O
+Ser	O
+Phe	O
+Gln	O
+Leu	O
+Glu	O
+Asp	O
+Ala	O
+Glu	O
+Asn	O
+Phe	O
+Ile	O
+Ser	O
+Asn	O
+Ile	O
+Arg	O
+Val	O
+Thr	O
+Val	O
+Val	O
+AAA	O
+CTA	O
+AAG	O
+GTAAGGTGTTGCTTTATTTG	O
+Lys	O
+Leu	O
+Lys	O
+
+CTTTGATGGGTTCTGTGCAT	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+1000	O
+bp	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+GAATTCTACAGAAGTGTTCA	O
+TATTTTTTATGCTTTACCAT	O
+
+CAGTGTTAAAATAAATGCCT	O
+
+450	O
+500	O
+
+GGC	O
+TCT	O
+GAC	O
+AAC	O
+ACA	O
+TTT	O
+GAG	O
+TGC	O
+CAA	O
+TTC	O
+GAT	O
+GAT	O
+GAG	O
+TCA	O
+GCA	O
+ACT	O
+GTG	O
+GTG	O
+GAC	O
+TTT	O
+CTG	O
+AGG	O
+AGA	O
+Gly	O
+Ser	O
+Asp	O
+Asn	O
+Thr	O
+Phe	O
+Glu	O
+Cys	O
+Gln	O
+Phe	O
+Asp	O
+Asp	O
+GlU	O
+Ser	O
+Ala	O
+Thr	O
+Val	O
+Val	O
+Asp	O
+Phe	O
+Leu	O
+Arg	O
+Arg	O
+
+550	O
+
+TGG	O
+ATA	O
+GCC	O
+TTC	O
+TGT	O
+CAA	O
+AGC	O
+ATC	O
+ATC	O
+TCA	O
+ACA	O
+AGC	O
+CCT	O
+CAA	O
+TAACTATGTACCTCCTGCTT	O
+Trp	O
+Ile	O
+Ala	O
+Phe	O
+Cys	O
+Gln	O
+Ser	O
+Ile	O
+Ile	O
+Ser	O
+Thr	O
+Ser	O
+Pro	O
+Gln	O
+
+600	O
+650	O
+
+TCTCTATTTAT4TAAATATT	O
+
+700	O
+750	O
+
+GATCTTTAAAGATTCTTTTT	O
++	O
+ATTATATTGAATTGTTAAAT	O
+
+<	O
+4	O
+>	O
+800	O
+850	O
+
+ATCATGTGTAGGTAGACTcA	O
+TAAAAGTAmAGATGATTCAA	O
+
+900	O
+0	O
+"	O
+
+TAAGCGCTAAAATAACTTCT	O
+AAA	O
+GATGGCTTGTGGGAAAAGAT	O
+
+Fig	O
+.	O
+
+3	O
+.	O
+
+Nucleotide	O
+sequence	O
+of	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+.	O
+
+Four	O
+exons	O
+are	O
+framed	O
+.	O
+
+Numbers	O
+refer	O
+to	O
+nucleotide	O
+positions	O
+of	O
+exons	O
+from	O
+the	O
+presumed	O
+cap	O
+site	O
+.	O
+
+Dots	O
+and	O
+open	O
+circles	O
+indicate	O
+TATA	O
+box	O
+and	O
+poly	O
+A	O
+additional	O
+signals	O
+,	O
+respectively	O
+.	O
+
+9328	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+-	O
+4	O
+5	O
+0	O
+-	O
+400	O
+
+TAGGAGGT	O
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+T	O
+CTCGAAAC	O
+GGAAACCAATATCCTTCCTG	O
+
+.	O
+0	O
+*	O
+.	O
+0	O
+.	O
+-	O
+*	O
+.	O
+
+*	O
+.	O
+.	O
+*	O
+-	O
+-	O
+.	O
+
+-	O
+-	O
+.	O
+*	O
+-	O
+@	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+.	O
+
+-	O
+-	O
+-	O
+*	O
+-	O
+*	O
+*	O
+
+TAAAAAGGTAAAACCAGTTC	O
+GAAACAGGAAACCAATACAC	O
+CATTTATTCTTTTCATCTGT	O
+
+-	O
+350	O
+-	O
+300	O
+
+TCTTGCGCCCGTCCACCACA	O
+T	O
+ACAGGTTCAGGATGGTTTTG	O
+TCTTGCTCTTGTTCACCACA	O
+TGCTATTCACATGTTCAGTG	O
+TGAGTTACTTTTGTATCCC	O
+
+-	O
+250	O
+
+CA	O
+CCCC	O
+AAAG	O
+AGGAAAATTTGTTTCATACG	O
+CCACCTAAGAGTGGGCTAAC	O
+
+*	O
+~	O
+~	O
+~	O
+~	O
+~	O
+.	O
+.	O
+.	O
+.	O
+.	O
+
+*	O
+.	O
+-	O
+-	O
+*	O
+.	O
+.	O
+-	O
+*	O
+.	O
+-	O
+-	O
+.	O
+*	O
+*	O
+.	O
+
+*	O
+-	O
+.	O
+
+-	O
+-	O
+.	O
+
+*	O
+-	O
+*	O
+-	O
+-	O
+-	O
+*	O
+-	O
+0	O
+@	O
+*	O
+-	O
+-	O
+0	O
+.	O
+.	O
+
+.	O
+
+CACCCCCTTAAAGAAAGGAG	O
+
+-	O
+200	O
+-	O
+150	O
+
+CCAAGAGGGATTTCACCTAA	O
+GGGGTTTAAACAAATTCCAG	O
+CAAAGAGGGATTTCACCTAC	O
+AAATTCCAAAGAGTCATCAG	O
+
+-	O
+100	O
+-	O
+50	O
+
+TACTTTCTGCCACACAGGTA	O
+TGTTTTTT	O
+CAGACAGGTAAAGTC	O
+TTTGAAAATATGTGTAATAT	O
+ATAAGCCTCCCATGCTGAAG	O
+Mouse	B
+rTATGCATCTCTTGTTCAAG	O
+Human	B
+
+Fig	O
+.	O
+
+4	O
+.	O
+
+Comparison	O
+of	O
+5	O
+'	O
+-	O
+flanking	O
+regions	O
+of	O
+mouse	B
+and	O
+human	B
+IL	O
+-	O
+2	O
+genes	O
+.	O
+
+In	O
+aligning	O
+the	O
+sequences	O
+for	O
+both	O
+genes	O
+,	O
+gaps	O
+were	O
+introduced	O
+to	O
+maximize	O
+homology	O
+.	O
+
+Dots	O
+indicate	O
+identical	O
+nucleotide	O
+sequences	O
+.	O
+
+Number	O
+1	O
+indicates	O
+putative	O
+transcription	O
+initiation	O
+site	O
+.	O
+
+Inverted	O
+repeats	O
+are	O
+indicated	O
+by	O
+bars	O
+and	O
+dashed	O
+lines	O
+.	O
+
+TATA	O
+box	O
+is	O
+framed	O
+.	O
+
+of	O
+both	O
+genes	O
+is	O
+illustrated	O
+in	O
+Fig	O
+.	O
+
+4	O
+.	O
+
+The	O
+nucleotide	O
+sequence	O
+homology	O
+from	O
+the	O
+TATA	O
+box	O
+to	O
+-	O
+470	O
+is	O
+85	O
+%	O
+.	O
+
+The	O
+highest	O
+region	O
+of	O
+homology	O
+was	O
+observed	O
+between	O
+the	O
+TATA	O
+box	O
+and	O
+position	O
+-	O
+97	O
+(	O
+60	O
+bp	O
+matches	O
+out	O
+of	O
+64	O
+bp	O
+)	O
+of	O
+both	O
+genes	O
+.	O
+
+DISCUSSION	O
+
+We	O
+have	O
+isolated	O
+recombinant	O
+clones	O
+for	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+from	O
+a	O
+phage	O
+Charon	O
+4A	O
+/	O
+mouse	B
+genomic	O
+DNA	O
+library	O
+and	O
+determined	O
+the	O
+entire	O
+sequence	O
+of	O
+the	O
+gene	O
+except	O
+for	O
+the	O
+sequence	O
+of	O
+the	O
+internal	O
+portion	O
+of	O
+the	O
+second	O
+and	O
+third	O
+introns	O
+.	O
+
+The	O
+mouse	B
+IL	O
+-	O
+2	O
+cDNA	O
+sequence	O
+was	O
+aligned	O
+with	O
+the	O
+genomic	O
+sequence	O
+and	O
+both	O
+sequences	O
+matched	O
+completely	O
+each	O
+other	O
+.	O
+
+The	O
+unusual	O
+CAG	O
+repeats	O
+encoding	O
+12	O
+glutamines	O
+which	O
+was	O
+found	O
+previously	O
+in	O
+the	O
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+cDNA	O
+was	O
+shown	O
+to	O
+be	O
+present	O
+also	O
+in	O
+the	O
+chromosomal	O
+gene	O
+.	O
+
+This	O
+finding	O
+further	O
+excludes	O
+the	O
+possibility	O
+that	O
+the	O
+unique	O
+repeat	O
+is	O
+generated	O
+by	O
+artifacts	O
+during	O
+the	O
+cDNA	O
+cloning	O
+process	O
+.	O
+
+Although	O
+we	O
+can	O
+not	O
+rule	O
+out	O
+the	O
+possibility	O
+for	O
+the	O
+deletion	O
+of	O
+this	O
+sequence	O
+in	O
+the	O
+human	B
+IL	O
+-	O
+2	O
+gene	O
+,	O
+it	O
+is	O
+more	O
+likely	O
+that	O
+the	O
+CAG	O
+repeat	O
+has	O
+been	O
+generated	O
+in	O
+the	O
+mouse	B
+genome	O
+rather	O
+recently	O
+.	O
+
+The	O
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+could	O
+have	O
+been	O
+generated	O
+either	O
+by	O
+a	O
+direct	O
+insertion	O
+of	O
+the	O
+sequence	O
+or	O
+by	O
+the	O
+duplication	O
+after	O
+insertion	O
+of	O
+a	O
+unit	O
+sequence	O
+.	O
+
+9329	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Organization	O
+of	O
+the	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+resembles	O
+to	O
+that	O
+of	O
+the	O
+human	B
+gene	O
+(	O
+Fig	O
+.	O
+2	O
+.	O
+,	O
+ref	O
+.	O
+9	O
+)	O
+.	O
+
+There	O
+seems	O
+to	O
+be	O
+little	O
+sequence	O
+homology	O
+between	O
+corresponding	O
+introns	O
+of	O
+mouse	B
+and	O
+human	B
+IL	O
+-	O
+2	O
+genes	O
+,	O
+except	O
+for	O
+the	O
+intron	O
+-	O
+exon	O
+junctions	O
+part	O
+of	O
+which	O
+is	O
+thought	O
+to	O
+be	O
+necessary	O
+for	O
+the	O
+RNA	O
+splicing	O
+(	O
+17	O
+,	O
+18	O
+)	O
+.	O
+
+Dissimilarity	O
+of	O
+the	O
+intron	O
+sequences	O
+among	O
+the	O
+genes	O
+which	O
+are	O
+derived	O
+from	O
+a	O
+common	O
+ancestor	O
+has	O
+been	O
+reported	O
+in	O
+other	O
+genes	O
+(	O
+19	O
+,	O
+20	O
+)	O
+.	O
+
+In	O
+spite	O
+of	O
+the	O
+divergence	O
+in	O
+sequence	O
+of	O
+introns	O
+,	O
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+the	O
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+very	O
+similar	O
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+the	O
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+and	O
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+IL	O
+-	O
+2	O
+genes	O
+.	O
+
+Of	O
+particular	O
+interests	O
+is	O
+the	O
+presence	O
+of	O
+highly	O
+conserved	O
+sequences	O
+in	O
+the	O
+5	O
+'	O
+-	O
+flanking	O
+region	O
+of	O
+the	O
+human	B
+and	O
+mouse	B
+IL	O
+-	O
+2	O
+gene	O
+(	O
+Fig	O
+.	O
+4	O
+)	O
+.	O
+
+Whereas	O
+the	O
+coding	O
+region	O
+shows	O
+nucleotide	O
+sequence	O
+homology	O
+of	O
+72	O
+%	O
+between	O
+the	O
+two	O
+genes	O
+,	O
+the	O
+5	O
+'	O
+upstream	O
+region	O
+spanning	O
+about	O
+500	O
+bp	O
+(	O
+Fig	O
+.	O
+4	O
+)	O
+shows	O
+85	O
+%	O
+homology	O
+which	O
+was	O
+readily	O
+detectable	O
+by	O
+the	O
+blotting	O
+analysis	O
+(	O
+Fig	O
+.	O
+1	O
+,	O
+lane	O
+1	O
+-	O
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+)	O
+.	O
+
+Since	O
+we	O
+have	O
+not	O
+yet	O
+determined	O
+the	O
+nucleotide	O
+sequence	O
+further	O
+upstream	O
+of	O
+the	O
+mouse	B
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+,	O
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+do	O
+not	O
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+not	O
+this	O
+similarity	O
+extends	O
+further	O
+.	O
+
+It	O
+is	O
+likely	O
+that	O
+such	O
+sequences	O
+are	O
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+in	O
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+of	O
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+-	O
+2	O
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+-	O
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+.	O
+
+Work	O
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+in	O
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+into	O
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+.	O
+
+Our	O
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+-	O
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+T	O
+-	O
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+Fujita	O
+&	O
+Taniguchi	O
+,	O
+unpublished	O
+observation	O
+)	O
+.	O
+
+ACKNOWLEDGEMENTS	O
+
+We	O
+thank	O
+Dr	O
+.	O
+T	O
+.	O
+
+Honjo	O
+for	O
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+.	O
+
+We	O
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+to	O
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+
+Nagatsuka	O
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+This	O
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+-	O
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+,	O
+Cancer	O
+-	O
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+Ministry	O
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+Education	O
+,	O
+Science	O
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+Culture	O
+,	O
+Japan	O
+.	O
+
+?	O
+To	O
+whom	O
+correspondence	O
+should	O
+be	O
+addressed	O
+
+*	O
+Present	O
+address	O
+:	O
+Department	O
+of	O
+Microbiology	O
+,	O
+School	O
+of	O
+Medicine	O
+,	O
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+University	O
+,	O
+Chiba	O
+280	O
+,	O
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+
++	O
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+address	O
+:	O
+Central	O
+Research	O
+Laboratory	O
+,	O
+Ajinomoto	O
+Co	O
+.	O
+Inc	O
+.	O
+,	O
+Totsuka	O
+-	O
+ku	O
+,	O
+Yokohama	O
+244	O
+,	O
+Japan	O
+
+9330	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+REFERENCES	O
+
+1	O
+.	O
+
+Morgan	O
+,	O
+D	O
+.	O
+
+A	O
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+,	O
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+
+W	O
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+,	O
+R	O
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+
+(	O
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+,	O
+
+193	O
+,	O
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+2	O
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+Gil	O
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+
+Ferm	O
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+
+M	O
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+,	O
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+,	O
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+(	O
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+
+Immunol	O
+.	O
+,	O
+120	O
+,	O
+2023	O
+-	O
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+
+3	O
+.	O
+
+Chen	O
+,	O
+B	O
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+
+M	O
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+,	O
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+
+(	O
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+)	O
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+
+Immunol	O
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+,	O
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+,	O
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+
+224	O
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+
+4	O
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+
+Henney	O
+,	O
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+.	O
+
+S	O
+.	O
+,	O
+Kuribayashi	O
+,	O
+K	O
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+,	O
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+,	O
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+.	O
+
+E	O
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+Gillis	O
+,	O
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+
+(	O
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+)	O
+Nature	O
+,	O
+291	O
+,	O
+335	O
+-	O
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+
+5	O
+.	O
+
+Wagner	O
+,	O
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+,	O
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+,	O
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+,	O
+Heeg	O
+,	O
+K	O
+.	O
+,	O
+Rollinghoff	O
+,	O
+M	O
+.	O
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+
+Pfizenmaier	O
+,	O
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+
+(	O
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+)	O
+Nature	O
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+284	O
+,	O
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+-	O
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+
+6	O
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+
+Farrar	O
+,	O
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+
+J	O
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+,	O
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+,	O
+W	O
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+
+R	O
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+,	O
+Hilfikr	O
+M	O
+.	O
+
+L	O
+.	O
+,	O
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+,	O
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+.	O
+,	O
+
+Farrar	O
+,	O
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+
+L	O
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+,	O
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+
+(	O
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+)	O
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+
+Rev	O
+.	O
+
+63	O
+,	O
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+-	O
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+
+7	O
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+
+Pearlstein	O
+,	O
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+,	O
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+,	O
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+
+A	O
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+,	O
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+,	O
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+,	O
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+
+(	O
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+)	O
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+
+Immunol	O
+.	O
+,	O
+80	O
+,	O
+1	O
+-	O
+9	O
+.	O
+
+8	O
+.	O
+
+Taniguchi	O
+,	O
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+,	O
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+,	O
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+,	O
+Fujita	O
+,	O
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+,	O
+Takaoka	O
+,	O
+C	O
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+,	O
+Kashima	O
+,	O
+
+N	O
+.	O
+,	O
+Yoshimoto	O
+,	O
+R	O
+.	O
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+Hamuro	O
+,	O
+J	O
+.	O
+
+(	O
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+)	O
+Nature	O
+302	O
+,	O
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+-	O
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+.	O
+
+9	O
+.	O
+
+Fujita	O
+,	O
+T	O
+.	O
+,	O
+Takaoka	O
+,	O
+C	O
+.	O
+,	O
+Matsui	O
+,	O
+H	O
+.	O
+and	O
+Taniguchi	O
+T	O
+.	O
+
+(	O
+1983	O
+)	O
+
+Proc	O
+.	O
+
+Natl	O
+.	O
+
+Acad	O
+.	O
+
+Sci	O
+.	O
+
+USA	O
+80	O
+,	O
+7437	O
+-	O
+7411	O
+.	O
+
+10	O
+.	O
+
+Ohno	O
+,	O
+S	O
+.	O
+and	O
+Taniguchi	O
+,	O
+T	O
+.	O
+
+(	O
+1982	O
+)	O
+Nucleic	O
+Acids	O
+Res	O
+.	O
+
+10	O
+,	O
+967	O
+
+977	O
+.	O
+
+11	O
+.	O
+
+Southern	O
+,	O
+E	O
+.	O
+
+M	O
+.	O
+
+(	O
+1975	O
+)	O
+J	O
+.	O
+
+Mol	O
+.	O
+
+Biol	O
+.	O
+
+98	O
+,	O
+503	O
+-	O
+517	O
+.	O
+
+12	O
+.	O
+
+Benton	O
+,	O
+W	O
+.	O
+
+D	O
+.	O
+and	O
+Davis	O
+,	O
+R	O
+.	O
+
+W	O
+.	O
+
+(	O
+1977	O
+)	O
+Science	O
+196	O
+,	O
+180	O
+-	O
+182	O
+.	O
+
+13	O
+.	O
+
+Ohno	O
+,	O
+S	O
+.	O
+and	O
+Taniguchi	O
+,	O
+T	O
+.	O
+
+(	O
+1981	O
+)	O
+Proc	O
+.	O
+
+Natl	O
+.	O
+
+Acad	O
+.	O
+
+Sci	O
+.	O
+
+USA	O
+
+78	O
+,	O
+5305	O
+-	O
+5309	O
+.	O
+
+14	O
+.	O
+
+Maxam	O
+,	O
+A	O
+.	O
+
+M	O
+.	O
+and	O
+Gilbert	O
+,	O
+W	O
+.	O
+
+(	O
+1980	O
+)	O
+Meth	O
+.	O
+
+Enzymol	O
+.	O
+
+65	O
+,	O
+560	O
+
+580	O
+.	O
+
+15	O
+.	O
+
+Sanger	O
+,	O
+F	O
+.	O
+,	O
+Nicklen	O
+,	O
+S	O
+.	O
+and	O
+Coulson	O
+,	O
+A	O
+.	O
+
+R	O
+.	O
+
+(	O
+1977	O
+)	O
+Proc	O
+.	O
+
+Natl	O
+.	O
+
+Acad	O
+.	O
+
+Sci	O
+.	O
+
+USA	O
+,	O
+74	O
+,	O
+5463	O
+-	O
+5467	O
+.	O
+
+16	O
+.	O
+
+Gillis	O
+,	O
+S	O
+.	O
+,	O
+Scheid	O
+,	O
+M	O
+.	O
+and	O
+Watson	O
+,	O
+J	O
+.	O
+
+D	O
+.	O
+(	O
+1980	O
+)	O
+J	O
+.	O
+
+Immunol	O
+.	O
+
+,	O
+125	O
+,	O
+2570	O
+-	O
+2580	O
+.	O
+
+17	O
+.	O
+
+Breathnach	O
+,	O
+R	O
+.	O
+,	O
+Benoist	O
+,	O
+C	O
+.	O
+,	O
+O	O
+'	O
+Hare	O
+,	O
+K	O
+.	O
+,	O
+Gannon	O
+,	O
+F	O
+.	O
+and	O
+
+Chambon	O
+,	O
+P	O
+.	O
+(	O
+1978	O
+)	O
+Proc	O
+.	O
+
+Natl	O
+.	O
+
+Acad	O
+.	O
+
+Sci	O
+.	O
+
+USA	O
+,	O
+75	O
+,	O
+4853	O
+-	O
+4857	O
+.	O
+
+18	O
+.	O
+
+Lerner	O
+,	O
+M	O
+.	O
+
+R	O
+.	O
+,	O
+Boyle	O
+,	O
+J	O
+.	O
+
+A	O
+.	O
+,	O
+Mount	O
+,	O
+S	O
+.	O
+
+M	O
+.	O
+,	O
+Wolin	O
+,	O
+S	O
+.	O
+
+L	O
+.	O
+and	O
+
+Steitz	O
+,	O
+J	O
+.	O
+
+A	O
+.	O
+
+(	O
+1980	O
+)	O
+Nature	O
+,	O
+283	O
+,	O
+220	O
+-	O
+224	O
+.	O
+
+19	O
+.	O
+
+Van	O
+Ooyen	O
+,	O
+A	O
+.	O
+,	O
+Van	O
+den	O
+Berg	O
+,	O
+J	O
+.	O
+,	O
+Mantei	O
+,	O
+N	O
+.	O
+and	O
+Weissmann	O
+,	O
+
+C	O
+.	O
+(	O
+1979	O
+)	O
+Science	O
+,	O
+206	O
+,	O
+337	O
+-	O
+344	O
+.	O
+
+20	O
+.	O
+
+Searle	O
+,	O
+P	O
+.	O
+
+F	O
+.	O
+,	O
+Davison	O
+,	O
+B	O
+.	O
+
+L	O
+.	O
+,	O
+Stuart	O
+,	O
+G	O
+.	O
+
+W	O
+.	O
+,	O
+Wilkie	O
+,	O
+T	O
+.	O
+
+M	O
+.	O
+,	O
+
+Norstedt	O
+,	O
+G	O
+.	O
+and	O
+Palmiter	O
+,	O
+R	O
+.	O
+
+D	O
+.	O
+
+(	O
+1984	O
+)	O
+Mol	O
+.	O
+
+Cell	O
+.	O
+
+Biol	O
+.	O
+
+4	O
+,	O
+1221	O
+-	O
+1230	O
+.	O
+
+9331	O
+
+Preparation	O
+of	O
+oligodeoxyribonucleo	O
+methylphosphonates	O
+on	O
+a	O
+polystyrene	O
+support	O
+.	O
+
+Abstract	O
+
+An	O
+efficient	O
+procedure	O
+is	O
+described	O
+for	O
+synthesizing	O
+deoxyribonucleoside	O
+methylphosphonates	O
+on	O
+polystyrene	O
+polymer	O
+supports	O
+which	O
+involves	O
+condensing	O
+5	O
+'	O
+-	O
+dimethoxytrityldeoxy	O
+3	O
+'	O
+-	O
+methylphosphonates	O
+.	O
+
+The	O
+oligomers	O
+are	O
+removed	O
+from	O
+the	O
+support	O
+and	O
+the	O
+base	O
+protecting	O
+groups	O
+hydrolyzed	O
+by	O
+treatment	O
+with	O
+ethylenediamine	O
+in	O
+ethanol	O
+,	O
+which	O
+avoids	O
+hydrolysis	O
+of	O
+the	O
+methylphosphonate	O
+linkages	O
+.	O
+
+Two	O
+types	O
+of	O
+oligomers	O
+were	O
+synthesized	O
+:	O
+those	O
+containing	O
+only	O
+methylphosphonate	O
+linkages	O
+,	O
+d	O
+-	O
+Np	O
+(	O
+Np	O
+)	O
+nN	O
+,	O
+and	O
+those	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+nucleotide	O
+residue	O
+,	O
+dNp	O
+(	O
+Np	O
+)	O
+nN	O
+.	O
+
+The	O
+latter	O
+oligomers	O
+can	O
+be	O
+phosphorylated	O
+by	O
+polynucleotide	O
+kinase	O
+,	O
+and	O
+are	O
+separated	O
+by	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+according	O
+to	O
+their	O
+chain	O
+length	O
+.	O
+
+Piperdine	O
+randomly	O
+cleaves	O
+the	O
+oligomer	O
+methylphosphonate	O
+linkages	O
+and	O
+generates	O
+a	O
+series	O
+of	O
+shorter	O
+oligomers	O
+whose	O
+number	O
+corresponds	O
+to	O
+the	O
+length	O
+of	O
+the	O
+original	O
+oligomer	O
+.	O
+
+Apurinic	O
+sites	O
+introduced	O
+by	O
+acid	O
+treatment	O
+spontaneously	O
+hydrolyze	O
+to	O
+give	O
+oligomers	O
+which	O
+terminate	O
+with	O
+free	O
+3	O
+'	O
+and	O
+5	O
+'	O
+OH	O
+groups	O
+.	O
+
+These	O
+reactions	O
+may	O
+be	O
+used	O
+to	O
+characterize	O
+the	O
+oligomers	O
+.	O
+Images	O
+
+Vlue1Nubr1193NcecAis	O
+
+Preparation	O
+of	O
+oligodeoxyribonucleo	O
+methylphosphonates	O
+on	O
+a	O
+polystyrene	O
+support	O
+P	O
+.	O
+S	O
+.	O
+Miller	O
+,	O
+C	O
+.	O
+H	O
+.	O
+Agris	O
+,	O
+A	O
+.	O
+Murakami	O
+,	O
+P	O
+.	O
+M	O
+.	O
+Reddy	O
+,	O
+S	O
+.	O
+A	O
+.	O
+Spitz	O
+and	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+Ts	O
+'	O
+o	O
+
+Division	O
+of	O
+Biophysics	O
+,	O
+Johns	O
+Hopkins	O
+University	O
+,	O
+School	O
+of	O
+Hygiene	O
+and	O
+Public	O
+Health	O
+,	O
+Baltimore	O
+,	O
+MD	O
+21205	O
+,	O
+USA	O
+
+Received	O
+26	O
+July	O
+1983	O
+;	O
+Accepted	O
+5	O
+September	O
+1983	O
+
+ABSTRACT	O
+
+An	O
+efficient	O
+procedure	O
+is	O
+described	O
+for	O
+synthesizing	O
+deoxyribonucleoside	O
+methylphosphonates	O
+on	O
+polystyrene	O
+polyner	O
+supports	O
+which	O
+involves	O
+condensing	O
+5	O
+'	O
+-	O
+dimethoxytrityldeoxy	O
+3	O
+'	O
+-	O
+methylphosphonates	O
+.	O
+
+The	O
+oligomers	O
+are	O
+removed	O
+from	O
+the	O
+support	O
+and	O
+the	O
+base	O
+protecting	O
+groups	O
+hydrolyzed	O
+by	O
+
+treatment	O
+with	O
+ethylenediamine	O
+in	O
+ethanol	O
+,	O
+which	O
+avoids	O
+hydrolysis	O
+of	O
+the	O
+
+methylphosphonate	O
+linkages	O
+.	O
+
+Two	O
+types	O
+of	O
+oligomers	O
+were	O
+synthesized	O
+:	O
+those	O
+containing	O
+only	O
+methylphosphonate	O
+linkages	O
+,	O
+d	O
+-	O
+Np	O
+(	O
+Np	O
+)	O
+N	O
+,	O
+and	O
+those	O
+which	O
+
+terminate	O
+with	O
+a	O
+5	O
+'	O
+nucleotide	O
+residue	O
+,	O
+dNp	O
+(	O
+Np	O
+)	O
+N	O
+.	O
+-	O
+J	O
+he	O
+latter	O
+oligomers	O
+can	O
+be	O
+phosphorylated	O
+by	O
+polynucleotide	O
+kinase	O
+,	O
+and	O
+are	O
+separated	O
+by	O
+
+polyacrylamide	O
+gel	O
+electrophoresis	O
+according	O
+to	O
+their	O
+chain	O
+length	O
+.	O
+
+Piperdine	O
+randomly	O
+cleaves	O
+the	O
+oligomer	O
+methylphosphonate	O
+linkages	O
+and	O
+generates	O
+a	O
+
+series	O
+of	O
+shorter	O
+oligomers	O
+whose	O
+number	O
+corresponds	O
+to	O
+the	O
+length	O
+of	O
+the	O
+
+original	O
+oligomer	O
+.	O
+
+Apurinic	O
+sites	O
+introduced	O
+by	O
+acid	O
+treatment	O
+spontaneously	O
+hydrolyze	O
+to	O
+give	O
+oligomers	O
+which	O
+terminate	O
+with	O
+free	O
+3	O
+'	O
+and	O
+5	O
+'	O
+OH	O
+groups	O
+.	O
+
+These	O
+reactions	O
+may	O
+be	O
+used	O
+to	O
+characterize	O
+the	O
+oligomers	O
+.	O
+
+INTRODUCTION	O
+
+Oligonucleoside	O
+methylphosphonates	O
+have	O
+been	O
+used	O
+to	O
+st	O
+-	O
+udy	O
+the	O
+function	O
+of	O
+specific	O
+RNA	O
+sequences	O
+in	O
+biochemical	O
+and	O
+intact	O
+cellular	O
+systems	O
+(	O
+1	O
+,	O
+2	O
+)	O
+.	O
+
+Since	O
+these	O
+nonionic	O
+nucleic	O
+acid	O
+analogs	O
+can	O
+be	O
+taken	O
+up	O
+intact	O
+by	O
+mammalian	O
+cells	O
+and	O
+certain	O
+bacterial	O
+cells	O
+in	O
+culture	O
+,	O
+these	O
+compounds	O
+promise	O
+to	O
+be	O
+useful	O
+reagents	O
+for	O
+exploring	O
+and	O
+regulating	O
+the	O
+function	O
+of	O
+nucleic	O
+acids	O
+within	O
+living	O
+cells	O
+.	O
+
+In	O
+order	O
+to	O
+carry	O
+out	O
+more	O
+extensive	O
+biochemical	O
+and	O
+biological	O
+studies	O
+,	O
+an	O
+efficient	O
+method	O
+for	O
+synthesis	O
+of	O
+oligonucleoside	O
+methylphosphonates	O
+of	O
+defined	O
+sequence	O
+is	O
+needed	O
+.	O
+
+Previously	O
+we	O
+described	O
+the	O
+synthesis	O
+of	O
+
+methylphosphonate	O
+analogs	O
+on	O
+a	O
+silica	O
+gel	O
+support	O
+(	O
+3	O
+)	O
+.	O
+
+Protected	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphonic	O
+chlorides	O
+or	O
+tetrazolides	O
+were	O
+used	O
+as	O
+synthetic	O
+
+intermediates	O
+.	O
+
+While	O
+oligothymidine	O
+methylphosphonates	O
+could	O
+be	O
+efficiently	O
+synthesized	O
+by	O
+this	O
+procedure	O
+,	O
+low	O
+yields	O
+were	O
+encountered	O
+when	O
+other	O
+
+nucleosides	O
+,	O
+particularly	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ibuG	O
+were	O
+used	O
+.	O
+
+Recently	O
+Sinha	O
+et	O
+al	O
+.	O
+
+?	O
+)	O
+I	O
+RL	O
+Press	O
+Limited	O
+,	O
+Oxford	O
+,	O
+England	O
+.	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Volume	O
+1	O
+1	O
+Number	O
+18	O
+1983	O
+
+6225	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+described	O
+the	O
+preparation	O
+of	O
+oligonucleoside	O
+methylphosphophonate	O
+on	O
+a	O
+glass	O
+support	O
+using	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphine	O
+chlorides	O
+as	O
+reactive	O
+intermediates	O
+(	O
+4	O
+)	O
+.	O
+
+In	O
+this	O
+paper	O
+we	O
+describe	O
+a	O
+set	O
+of	O
+useful	O
+methods	O
+for	O
+the	O
+synthesis	O
+and	O
+analysis	O
+of	O
+these	O
+analogs	O
+.	O
+
+The	O
+synthesis	O
+involves	O
+condensation	O
+of	O
+protected	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphonate	O
+triethylammonium	O
+salts	O
+with	O
+nucleosides	O
+or	O
+
+oligomers	O
+linked	O
+to	O
+a	O
+polystyrene	O
+support	O
+.	O
+
+This	O
+method	O
+has	O
+proven	O
+to	O
+be	O
+easy	O
+to	O
+use	O
+and	O
+allows	O
+relatively	O
+rapid	O
+synthesis	O
+of	O
+oligomers	O
+of	O
+defined	O
+sequence	O
+up	O
+to	O
+nine	O
+nucleosides	O
+in	O
+length	O
+.	O
+
+We	O
+have	O
+also	O
+developed	O
+conditions	O
+for	O
+the	O
+
+efficient	O
+removal	O
+of	O
+base	O
+protecting	O
+groups	O
+and	O
+subsequent	O
+purification	O
+of	O
+the	O
+oligomers	O
+.	O
+
+A	O
+novel	O
+hydrolysis	O
+reaction	O
+which	O
+can	O
+be	O
+used	O
+as	O
+a	O
+basis	O
+for	O
+
+characterizing	O
+and	O
+sequencing	O
+these	O
+oligonucleotide	O
+analogs	O
+occurs	O
+at	O
+apurinic	O
+sites	O
+created	O
+by	O
+acid	O
+treatment	O
+of	O
+the	O
+oligomers	O
+.	O
+
+EXPERIMENTAL	O
+
+Materials	O
+and	O
+Methods	O
+
+Protected	O
+nucleosides	O
+,	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+N	O
+,	O
+were	O
+purchased	O
+from	O
+P	O
+.	O
+L	O
+.	O
+
+Biochemicals	O
+and	O
+were	O
+used	O
+without	O
+further	O
+purification	O
+.	O
+
+Protected	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphonate	O
+triethylammoni	O
+um	O
+salts	O
+,	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+Np	O
+*	O
+Et3NH	O
+,	O
+were	O
+
+prepared	O
+as	O
+previously	O
+described	O
+(	O
+3	O
+)	O
+.	O
+
+5	O
+-	O
+Dimethoxytrityl	O
+protected	O
+nucleosides	O
+esterified	O
+to	O
+1	O
+%	O
+or	O
+2	O
+%	O
+crosslinked	O
+polystyrene	O
+were	O
+purchased	O
+from	O
+Chem	O
+Genes	O
+Inc	O
+.	O
+
+The	O
+nucleoside	O
+loading	O
+level	O
+was	O
+40	O
+to	O
+120	O
+pmol	O
+of	O
+
+nucleoside	O
+/	O
+g	O
+of	O
+support	O
+.	O
+
+Mesitylenesulfonyl	O
+-	O
+3	O
+-	O
+nitrotriazole	O
+(	O
+MSNT	O
+)	O
+was	O
+purchased	O
+from	O
+Vega	O
+Biochemicals	O
+.	O
+
+Anhydrous	O
+pyridine	O
+was	O
+prepared	O
+by	O
+
+refluxing	O
+previously	O
+purified	O
+pyridine	O
+(	O
+5	O
+)	O
+over	O
+calcium	O
+hydride	O
+chips	O
+for	O
+several	O
+hours	O
+followed	O
+by	O
+distillation	O
+onto	O
+calcium	O
+hydride	O
+chips	O
+in	O
+5	O
+ml	O
+V	O
+-	O
+vials	O
+fitted	O
+with	O
+Teflon	O
+-	O
+lined	O
+septum	O
+caps	O
+(	O
+Wheaton	O
+Scientific	O
+)	O
+.	O
+
+Lyophilized	O
+spleen	O
+phosphodiesterase	O
+was	O
+obtained	O
+from	O
+P	O
+.	O
+L	O
+.	O
+
+Biochemicals	O
+.	O
+
+T	O
+-	O
+4	O
+polynucleotide	O
+kinase	O
+and	O
+[	O
+y	O
+-	O
+32P	O
+]	O
+-	O
+ATP	O
+were	O
+obtained	O
+from	O
+New	O
+England	O
+Nuclear	O
+.	O
+
+Reversed	O
+phase	O
+high	O
+performance	O
+liquid	O
+chromatography	O
+(	O
+HPLC	O
+)	O
+was	O
+carried	O
+out	O
+on	O
+Whatman	O
+Inc	O
+.	O
+
+C	O
+-	O
+18	O
+(	O
+ODS	O
+-	O
+3	O
+)	O
+columns	O
+(	O
+0	O
+.	O
+4	O
+x	O
+25	O
+cm	O
+)	O
+.	O
+
+Analytical	O
+columns	O
+were	O
+
+eluted	O
+with	O
+50	O
+ml	O
+linear	O
+gradients	O
+of	O
+acetonitrile	O
+in	O
+water	O
+or	O
+acetonitrile	O
+in	O
+0	O
+.	O
+1	O
+M	O
+ammonium	O
+acetate	O
+(	O
+pH	O
+5	O
+.	O
+8	O
+)	O
+at	O
+a	O
+flow	O
+rate	O
+of	O
+2	O
+.	O
+5	O
+ml	O
+/	O
+min	O
+.	O
+
+The	O
+eluate	O
+was	O
+
+monitored	O
+at	O
+254	O
+nm	O
+.	O
+
+The	O
+following	O
+molar	O
+extinction	O
+coefficients	O
+were	O
+used	O
+at	O
+254	O
+nm	O
+:	O
+d	O
+-	O
+T	O
+7	O
+,	O
+250	O
+,	O
+dA	O
+13	O
+,	O
+270	O
+,	O
+dC	O
+6	O
+,	O
+260	O
+,	O
+dG	O
+13	O
+,	O
+700	O
+.	O
+
+Unless	O
+otherwise	O
+noted	O
+,	O
+all	O
+reactions	O
+and	O
+operations	O
+were	O
+carried	O
+out	O
+at	O
+room	O
+temperature	O
+.	O
+
+General	O
+Procedure	O
+for	O
+Preparing	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+The	O
+
+following	O
+procedure	O
+represents	O
+the	O
+current	O
+method	O
+used	O
+in	O
+our	O
+laboratory	O
+to	O
+
+6226	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+synthesize	O
+methylphosphonate	O
+oligomers	O
+.	O
+
+Table	O
+I	O
+lists	O
+some	O
+of	O
+the	O
+oligomers	O
+which	O
+have	O
+been	O
+synthesized	O
+on	O
+polystyrene	O
+supports	O
+.	O
+
+Oligomers	O
+7	O
+,	O
+8	O
+,	O
+and	O
+10	O
+were	O
+synthesized	O
+as	O
+described	O
+below	O
+.	O
+
+The	O
+other	O
+oligomers	O
+were	O
+synthesized	O
+in	O
+essentially	O
+the	O
+same	O
+manner	O
+except	O
+the	O
+condensation	O
+reactions	O
+were	O
+run	O
+in	O
+1	O
+ml	O
+V	O
+-	O
+vials	O
+or	O
+in	O
+glass	O
+reaction	O
+columns	O
+purchased	O
+from	O
+Bachem	O
+Inc	O
+.	O
+
+When	O
+the	O
+
+reactions	O
+were	O
+run	O
+in	O
+V	O
+-	O
+vials	O
+,	O
+the	O
+support	O
+was	O
+dried	O
+by	O
+several	O
+evaporations	O
+
+with	O
+anhydrous	O
+pyridine	O
+in	O
+the	O
+V	O
+-	O
+vial	O
+(	O
+3	O
+)	O
+.	O
+
+When	O
+the	O
+reactions	O
+were	O
+run	O
+in	O
+the	O
+glass	O
+reaction	O
+column	O
+,	O
+the	O
+support	O
+was	O
+dried	O
+by	O
+a	O
+single	O
+evaporation	O
+with	O
+anhydrous	O
+pyridine	O
+overnight	O
+at	O
+room	O
+temperature	O
+.	O
+
+Synthesis	O
+of	O
+Protected	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+The	O
+synthetic	O
+
+reactions	O
+are	O
+most	O
+conveniently	O
+carried	O
+out	O
+in	O
+a	O
+polypropylene	O
+col	O
+umn	O
+(	O
+Bio	O
+Rad	O
+Econo	O
+column	O
+)	O
+fitted	O
+with	O
+a	O
+Teflon	O
+3	O
+-	O
+way	O
+valve	O
+(	O
+Bio	O
+Rad	O
+)	O
+and	O
+a	O
+rubber	O
+septum	O
+cap	O
+(	O
+Wheaton	O
+Scientific	O
+)	O
+.	O
+
+During	O
+washing	O
+operations	O
+,	O
+the	O
+septum	O
+cap	O
+is	O
+removed	O
+and	O
+the	O
+3	O
+-	O
+way	O
+valve	O
+is	O
+connected	O
+to	O
+a	O
+filter	O
+flask	O
+via	O
+a	O
+Luerer	O
+
+adaptor	O
+and	O
+tubing	O
+set	O
+(	O
+Bio	O
+Rad	O
+)	O
+.	O
+
+Generally	O
+vacuum	O
+is	O
+not	O
+required	O
+to	O
+wash	O
+
+the	O
+support	O
+.	O
+
+During	O
+the	O
+drying	O
+step	O
+,	O
+one	O
+port	O
+of	O
+the	O
+3	O
+-	O
+way	O
+valve	O
+is	O
+connected	O
+to	O
+a	O
+cold	O
+trap	O
+and	O
+vacuum	O
+pump	O
+via	O
+the	O
+barrel	O
+of	O
+a	O
+1	O
+ml	O
+plastic	O
+syringe	O
+.	O
+
+The	O
+other	O
+port	O
+is	O
+connected	O
+to	O
+a	O
+Drierite	O
+column	O
+filled	O
+with	O
+dry	O
+argon	O
+.	O
+
+A	O
+reaction	O
+cycle	O
+consists	O
+of	O
+the	O
+following	O
+10	O
+steps	O
+:	O
+1	O
+)	O
+The	O
+support	O
+(	O
+60	O
+mg	O
+,	O
+1	O
+%	O
+crosslinked	O
+)	O
+in	O
+the	O
+column	O
+is	O
+washed	O
+with	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+
+methylene	O
+chloride	O
+/	O
+isopropanol	O
+(	O
+85	O
+:	O
+15	O
+,	O
+v	O
+/	O
+v	O
+)	O
+.	O
+
+2	O
+)	O
+The	O
+support	O
+is	O
+treated	O
+with	O
+2	O
+ml	O
+of	O
+1	O
+M	O
+zinc	O
+bromide	O
+in	O
+methylene	O
+chloride	O
+/	O
+isopropanol	O
+solution	O
+.	O
+
+Two	O
+fiveminute	O
+treatments	O
+are	O
+used	O
+when	O
+the	O
+support	O
+-	O
+bound	O
+nucleoside	O
+is	O
+
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzA	O
+or	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ibuG	O
+,	O
+while	O
+four	O
+treatments	O
+are	O
+used	O
+when	O
+the	O
+nucleoside	O
+is	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+T	O
+or	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzC	O
+.	O
+
+After	O
+each	O
+treatment	O
+the	O
+
+orange	O
+solution	O
+is	O
+collected	O
+in	O
+a	O
+clean	O
+flask	O
+.	O
+
+3	O
+)	O
+The	O
+support	O
+is	O
+washed	O
+with	O
+two	O
+2	O
+ml	O
+portions	O
+of	O
+methylene	O
+chloride	O
+/	O
+isopropanol	O
+and	O
+the	O
+washings	O
+are	O
+
+collected	O
+in	O
+same	O
+flask	O
+used	O
+in	O
+step	O
+2	O
+)	O
+.	O
+
+The	O
+solution	O
+is	O
+diluted	O
+to	O
+50	O
+ml	O
+and	O
+a	O
+0	O
+.	O
+20	O
+ml	O
+aliquot	O
+is	O
+dissolved	O
+in	O
+0	O
+.	O
+80	O
+ml	O
+of	O
+perchloric	O
+acid	O
+/	O
+ethanol	O
+(	O
+3	O
+:	O
+2	O
+,	O
+
+v	O
+/	O
+v	O
+)	O
+.	O
+
+The	O
+absorbance	O
+is	O
+determined	O
+at	O
+500	O
+nm	O
+and	O
+the	O
+amount	O
+of	O
+trityl	O
+cation	O
+is	O
+determined	O
+using	O
+a	O
+molar	O
+extinction	O
+coefficient	O
+of	O
+89	O
+,	O
+000	O
+.	O
+
+4	O
+)	O
+The	O
+column	O
+is	O
+attached	O
+to	O
+a	O
+waste	O
+flask	O
+and	O
+the	O
+support	O
+is	O
+washed	O
+with	O
+three	O
+2	O
+ml	O
+
+portions	O
+of	O
+0	O
+.	O
+5	O
+M	O
+triethylammonium	O
+acetate	O
+in	O
+dimethylformamide	O
+;	O
+three	O
+2	O
+ml	O
+
+portions	O
+of	O
+anhydrous	O
+pyridine	O
+and	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+diethyl	O
+ether	O
+.	O
+
+5	O
+)	O
+The	O
+column	O
+is	O
+fitted	O
+with	O
+the	O
+septum	O
+cap	O
+and	O
+set	O
+up	O
+in	O
+the	O
+drying	O
+mode	O
+under	O
+
+house	O
+vacuum	O
+for	O
+at	O
+least	O
+5	O
+min	O
+.	O
+
+6	O
+)	O
+The	O
+support	O
+is	O
+dried	O
+by	O
+adding	O
+300	O
+jl	O
+of	O
+anhydrous	O
+pyridine	O
+via	O
+a	O
+gas	O
+tight	O
+syringe	O
+(	O
+Hamilton	O
+)	O
+.	O
+
+After	O
+the	O
+support	O
+has	O
+swollen	O
+,	O
+the	O
+vacuum	O
+(	O
+oil	O
+pump	O
+)	O
+is	O
+applied	O
+and	O
+the	O
+support	O
+is	O
+warmed	O
+with	O
+a	O
+
+6227	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+stream	O
+of	O
+air	O
+from	O
+a	O
+hair	O
+dryer	O
+.	O
+
+Evaporation	O
+is	O
+continued	O
+for	O
+10	O
+min	O
+.	O
+
+Dry	O
+argon	O
+is	O
+then	O
+admitted	O
+and	O
+the	O
+drying	O
+operation	O
+is	O
+repeated	O
+two	O
+more	O
+times	O
+.	O
+
+7	O
+)	O
+The	O
+coupling	O
+mixture	O
+is	O
+prepared	O
+by	O
+dissolving	O
+0	O
+.	O
+20	O
+mmol	O
+of	O
+MSNT	O
+in	O
+320	O
+pl	O
+of	O
+anhydrous	O
+pyridine	O
+.	O
+
+The	O
+solution	O
+is	O
+then	O
+transferred	O
+to	O
+the	O
+vial	O
+
+containing	O
+0	O
+.	O
+06	O
+mmol	O
+of	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+Np	O
+-	O
+Et3NH	O
+.	O
+
+The	O
+nucleotide	O
+is	O
+dissolved	O
+by	O
+vortexing	O
+and	O
+the	O
+coupling	O
+solution	O
+is	O
+then	O
+added	O
+dropwise	O
+to	O
+the	O
+support	O
+.	O
+
+It	O
+is	O
+important	O
+to	O
+add	O
+the	O
+solution	O
+slowly	O
+and	O
+to	O
+allow	O
+the	O
+support	O
+to	O
+swell	O
+.	O
+
+Trapped	O
+gas	O
+bubbles	O
+may	O
+be	O
+removed	O
+by	O
+gently	O
+tapping	O
+the	O
+column	O
+.	O
+
+This	O
+entire	O
+operation	O
+is	O
+carried	O
+out	O
+using	O
+one	O
+predried	O
+syringe	O
+.	O
+
+The	O
+syringe	O
+is	O
+left	O
+in	O
+
+the	O
+V	O
+-	O
+vial	O
+while	O
+the	O
+reagents	O
+are	O
+being	O
+dissolved	O
+.	O
+
+8	O
+)	O
+The	O
+reaction	O
+mixture	O
+is	O
+kept	O
+at	O
+room	O
+temperature	O
+for	O
+two	O
+hrs	O
+.	O
+
+9	O
+)	O
+The	O
+column	O
+is	O
+set	O
+up	O
+in	O
+the	O
+
+washing	O
+mode	O
+and	O
+the	O
+support	O
+is	O
+washed	O
+with	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+anhydrous	O
+pyridine	O
+.	O
+
+The	O
+solution	O
+,	O
+which	O
+contains	O
+unreacted	O
+nucleoside	O
+
+3	O
+'	O
+-	O
+methylphosphonate	O
+and	O
+MSNT	O
+,	O
+is	O
+collected	O
+in	O
+a	O
+separate	O
+flask	O
+.	O
+
+A	O
+50	O
+%	O
+
+aqueous	O
+pyridine	O
+solution	O
+(	O
+1	O
+ml	O
+)	O
+is	O
+added	O
+and	O
+the	O
+solution	O
+is	O
+kept	O
+at	O
+40C	O
+for	O
+
+later	O
+purification	O
+and	O
+recovery	O
+of	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+Np	O
+.	O
+
+10	O
+)	O
+The	O
+support	O
+is	O
+treated	O
+with	O
+a	O
+solution	O
+containing	O
+2	O
+ml	O
+of	O
+anhydrous	O
+pyridine	O
+,	O
+1	O
+ml	O
+of	O
+acetic	O
+
+anhydride	O
+and	O
+20	O
+mg	O
+of	O
+dimethylaminopyridin	O
+for	O
+30	O
+min	O
+.	O
+
+(	O
+This	O
+step	O
+was	O
+not	O
+included	O
+for	O
+the	O
+synthesis	O
+of	O
+oligomer	O
+10	O
+)	O
+.	O
+
+11	O
+)	O
+Return	O
+to	O
+step	O
+1	O
+,	O
+for	O
+the	O
+next	O
+cycle	O
+.	O
+
+Removal	O
+of	O
+Base	O
+Protecting	O
+Groups	O
+.	O
+
+The	O
+following	O
+general	O
+procedure	O
+was	O
+found	O
+to	O
+be	O
+the	O
+most	O
+effective	O
+method	O
+for	O
+cleaving	O
+the	O
+oligonucleotide	O
+from	O
+the	O
+1	O
+%	O
+crosslinked	O
+support	O
+and	O
+for	O
+removing	O
+the	O
+base	O
+protecting	O
+groups	O
+with	O
+minimal	O
+hydrolysis	O
+of	O
+the	O
+phosphonate	O
+backbone	O
+.	O
+
+The	O
+following	O
+steps	O
+were	O
+used	O
+for	O
+
+deprotecting	O
+oligomers	O
+7	O
+,	O
+8	O
+and	O
+10	O
+.	O
+
+Oligomer	O
+9	O
+was	O
+deprotected	O
+in	O
+a	O
+similar	O
+
+fashion	O
+except	O
+step	O
+4	O
+)	O
+was	O
+carried	O
+out	O
+at	O
+650C	O
+for	O
+3	O
+hrs	O
+.	O
+
+For	O
+oligomers	O
+1	O
+-	O
+6	O
+,	O
+step	O
+3	O
+)	O
+was	O
+not	O
+included	O
+and	O
+step	O
+4	O
+)	O
+was	O
+carried	O
+out	O
+at	O
+650	O
+for	O
+3	O
+hrs	O
+.	O
+
+1	O
+)	O
+After	O
+the	O
+final	O
+condensation	O
+step	O
+the	O
+support	O
+(	O
+60	O
+mg	O
+)	O
+is	O
+washed	O
+with	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+anhydrous	O
+pyridine	O
+;	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+methylene	O
+
+chloride	O
+/	O
+isopropanol	O
+and	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+diethyl	O
+ether	O
+.	O
+
+The	O
+support	O
+is	O
+then	O
+dried	O
+under	O
+house	O
+vacuum	O
+.	O
+
+2	O
+)	O
+The	O
+support	O
+is	O
+swollen	O
+by	O
+addition	O
+of	O
+2	O
+ml	O
+of	O
+pyridine	O
+and	O
+the	O
+excess	O
+is	O
+removed	O
+under	O
+house	O
+vacuum	O
+.	O
+
+3	O
+)	O
+The	O
+support	O
+is	O
+treated	O
+with	O
+3	O
+ml	O
+of	O
+0	O
+.	O
+017	O
+M	O
+tetra	O
+-	O
+n	O
+-	O
+butylammonium	O
+fluoride	O
+in	O
+
+tetrahydrofuran	O
+/	O
+pyridine	O
+/	O
+water	O
+(	O
+8	O
+:	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+for	O
+40	O
+hrs	O
+at	O
+room	O
+temperature	O
+.	O
+
+No	O
+shaking	O
+is	O
+required	O
+.	O
+
+The	O
+support	O
+is	O
+then	O
+washed	O
+with	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+50	O
+%	O
+pyridine	O
+/	O
+water	O
+;	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+pyridine	O
+;	O
+and	O
+three	O
+2	O
+ml	O
+
+portions	O
+of	O
+methylene	O
+chloride	O
+/	O
+isopropanol	O
+.	O
+
+4	O
+)	O
+The	O
+support	O
+is	O
+treated	O
+with	O
+3	O
+ml	O
+of	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+for	O
+7	O
+hrs	O
+at	O
+room	O
+temperature	O
+
+6228	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+without	O
+shaking	O
+.	O
+
+The	O
+solution	O
+is	O
+collected	O
+and	O
+the	O
+support	O
+is	O
+washed	O
+with	O
+
+four	O
+2	O
+ml	O
+portions	O
+of	O
+pyridine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+and	O
+four	O
+2	O
+ml	O
+portions	O
+of	O
+N	O
+,	O
+N	O
+-	O
+dimethylformamide	O
+.	O
+
+The	O
+combined	O
+eluate	O
+and	O
+washings	O
+are	O
+evaporated	O
+at	O
+250C	O
+and	O
+the	O
+oily	O
+residue	O
+is	O
+co	O
+-	O
+evaporated	O
+several	O
+time	O
+with	O
+50	O
+%	O
+aqueous	O
+ethanol	O
+.	O
+
+Purification	O
+of	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+For	O
+oligomers	O
+which	O
+
+contain	O
+only	O
+methylphosphonate	O
+linkages	O
+(	O
+1	O
+-	O
+6	O
+)	O
+,	O
+the	O
+residue	O
+from	O
+step	O
+4	O
+)	O
+of	O
+the	O
+previous	O
+section	O
+is	O
+dissolved	O
+in	O
+a	O
+small	O
+volume	O
+of	O
+50	O
+%	O
+aqueous	O
+ethanol	O
+.	O
+
+The	O
+solution	O
+is	O
+chromatographed	O
+on	O
+a	O
+C	O
+-	O
+18	O
+reversed	O
+phase	O
+column	O
+(	O
+0	O
+.	O
+46	O
+cm	O
+x	O
+25	O
+cm	O
+
+for	O
+100	O
+A254	O
+units	O
+or	O
+less	O
+;	O
+0	O
+.	O
+9	O
+cm	O
+x	O
+50	O
+cm	O
+for	O
+more	O
+than	O
+100	O
+A254	O
+units	O
+)	O
+using	O
+a	O
+linear	O
+gradient	O
+of	O
+0	O
+%	O
+to	O
+25	O
+%	O
+(	O
+8	O
+-	O
+mer	O
+or	O
+less	O
+)	O
+or	O
+0	O
+%	O
+to	O
+35	O
+%	O
+(	O
+9	O
+mer	O
+)	O
+
+acetonitrile	O
+in	O
+water	O
+to	O
+remove	O
+non	O
+-	O
+tritylated	O
+oligomers	O
+.	O
+
+The	O
+desired	O
+
+tritylated	O
+oligomer	O
+is	O
+eluted	O
+with	O
+50	O
+%	O
+acetonitrile	O
+in	O
+water	O
+.	O
+
+The	O
+solvents	O
+are	O
+evaporated	O
+and	O
+the	O
+residue	O
+is	O
+treated	O
+with	O
+1	O
+ml	O
+of	O
+80	O
+%	O
+acetic	O
+acid	O
+in	O
+water	O
+for	O
+1	O
+hr	O
+at	O
+room	O
+temperature	O
+.	O
+
+The	O
+solvents	O
+are	O
+evaporated	O
+and	O
+the	O
+
+residue	O
+is	O
+repeatedly	O
+evaporated	O
+with	O
+ethanol	O
+to	O
+ensure	O
+complete	O
+removal	O
+of	O
+
+acetic	O
+acid	O
+.	O
+
+The	O
+oligomer	O
+is	O
+then	O
+purified	O
+by	O
+C	O
+-	O
+18	O
+reversed	O
+phase	O
+HPLC	O
+using	O
+a	O
+0	O
+%	O
+to	O
+25	O
+%	O
+or	O
+30	O
+%	O
+acetonitrile	O
+in	O
+water	O
+gradient	O
+.	O
+
+For	O
+oligomers	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+-	O
+nucleoside	O
+phosphodiester	O
+linkage	O
+(	O
+7	O
+-	O
+10	O
+)	O
+the	O
+residue	O
+from	O
+step	O
+4	O
+)	O
+described	O
+in	O
+the	O
+preceeding	O
+section	O
+is	O
+treated	O
+with	O
+80	O
+%	O
+acetic	O
+acid	O
+in	O
+water	O
+for	O
+15	O
+min	O
+at	O
+room	O
+temperature	O
+.	O
+
+After	O
+removal	O
+of	O
+the	O
+acetic	O
+acid	O
+by	O
+evaporation	O
+,	O
+the	O
+residue	O
+is	O
+dissolved	O
+in	O
+20	O
+ml	O
+of	O
+50	O
+%	O
+aqueous	O
+ethanol	O
+and	O
+the	O
+solution	O
+is	O
+passed	O
+through	O
+a	O
+DEAE	O
+cellulose	O
+column	O
+(	O
+2	O
+.	O
+5	O
+x	O
+8	O
+cm	O
+,	O
+bicarbonate	O
+form	O
+)	O
+which	O
+has	O
+been	O
+previously	O
+washed	O
+with	O
+50	O
+%	O
+aqueous	O
+ethanol	O
+.	O
+
+The	O
+column	O
+is	O
+monitored	O
+at	O
+254	O
+nm	O
+and	O
+washed	O
+with	O
+50	O
+%	O
+
+aqueous	O
+ethanol	O
+until	O
+the	O
+pen	O
+returns	O
+to	O
+the	O
+baseline	O
+.	O
+
+The	O
+desired	O
+oligomer	O
+is	O
+then	O
+eluted	O
+with	O
+0	O
+.	O
+15	O
+M	O
+triethylammonium	O
+bicarbonate	O
+in	O
+50	O
+%	O
+aqueous	O
+
+ethanol	O
+.	O
+
+The	O
+buffer	O
+is	O
+removed	O
+by	O
+evaporation	O
+and	O
+co	O
+-	O
+evaporated	O
+with	O
+50	O
+%	O
+
+aqueous	O
+ethanol	O
+.	O
+
+The	O
+oligomer	O
+is	O
+then	O
+further	O
+purified	O
+by	O
+C	O
+-	O
+18	O
+reversed	O
+phase	O
+HPLC	O
+using	O
+a	O
+0	O
+%	O
+to	O
+30	O
+%	O
+acetonitrile	O
+in	O
+0	O
+.	O
+10	O
+M	O
+ammonium	O
+acetate	O
+(	O
+pH	O
+5	O
+.	O
+8	O
+)	O
+
+gradient	O
+.	O
+
+The	O
+oligomer	O
+is	O
+freed	O
+of	O
+ammonium	O
+acetate	O
+by	O
+desalting	O
+on	O
+a	O
+Bio	O
+-	O
+Gel	O
+P	O
+-	O
+2	O
+column	O
+(	O
+1	O
+.	O
+5	O
+x	O
+20	O
+cm	O
+)	O
+.	O
+
+Removal	O
+of	O
+the	O
+5	O
+'	O
+-	O
+Terminal	O
+Nucleotide	O
+Unit	O
+.	O
+
+Oligomers	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+-	O
+nucleotide	O
+phosphodiester	O
+may	O
+be	O
+converted	O
+to	O
+the	O
+oligonucleoside	O
+
+methylphosphonate	O
+by	O
+the	O
+following	O
+procedure	O
+.	O
+
+The	O
+oligomer	O
+(	O
+3	O
+A254	O
+units	O
+)	O
+is	O
+dissolved	O
+in	O
+40	O
+pl	O
+of	O
+water	O
+and	O
+treated	O
+at	O
+370C	O
+for	O
+2	O
+hrs	O
+with	O
+10	O
+PI	O
+(	O
+1	O
+-	O
+2	O
+
+units	O
+)	O
+of	O
+spleen	O
+phosphodiesterase	O
+dissolved	O
+in	O
+water	O
+.	O
+
+The	O
+completeness	O
+of	O
+the	O
+reaction	O
+is	O
+determined	O
+by	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+The	O
+solution	O
+is	O
+then	O
+
+6229	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+diluted	O
+with	O
+50	O
+ul	O
+of	O
+water	O
+and	O
+passed	O
+through	O
+a	O
+DEAE	O
+cellulose	O
+column	O
+(	O
+0	O
+.	O
+5	O
+x	O
+1	O
+cm	O
+)	O
+.	O
+
+The	O
+column	O
+is	O
+washed	O
+with	O
+500	O
+Pl	O
+of	O
+water	O
+and	O
+the	O
+oligomer	O
+is	O
+recovered	O
+by	O
+lyophilization	O
+.	O
+
+Recovery	O
+of	O
+Protected	O
+Nucleoside	O
+3	O
+'	O
+-	O
+Methylphosphonates	O
+.	O
+
+The	O
+aqueous	O
+pyridine	O
+solution	O
+from	O
+step	O
+9	O
+)	O
+described	O
+in	O
+General	O
+Procedure	O
+for	O
+Preparing	O
+
+Oligonucleoside	O
+Methylphosphonates	O
+,	O
+is	O
+evaporated	O
+after	O
+addition	O
+of	O
+0	O
+.	O
+1	O
+ml	O
+of	O
+triethylamine	O
+.	O
+
+The	O
+residue	O
+is	O
+dissolved	O
+in	O
+50	O
+ml	O
+of	O
+chloroform	O
+and	O
+the	O
+
+solution	O
+is	O
+extracted	O
+twice	O
+with	O
+50	O
+ml	O
+of	O
+1	O
+M	O
+ammonium	O
+bicarbonate	O
+.	O
+
+The	O
+
+chloroform	O
+layer	O
+is	O
+dried	O
+over	O
+anhydrous	O
+sodium	O
+sulfate	O
+.	O
+
+Several	O
+drops	O
+of	O
+triethylamine	O
+are	O
+added	O
+to	O
+clarify	O
+the	O
+solution	O
+.	O
+
+After	O
+filtration	O
+the	O
+
+solvents	O
+are	O
+evaporated	O
+and	O
+the	O
+residue	O
+is	O
+evaporated	O
+with	O
+three	O
+2	O
+ml	O
+portions	O
+of	O
+anhydrous	O
+pyridine	O
+on	O
+an	O
+oil	O
+pump	O
+.	O
+
+The	O
+foamy	O
+residue	O
+is	O
+dissolved	O
+in	O
+2	O
+ml	O
+of	O
+dry	O
+methylene	O
+chloride	O
+and	O
+the	O
+solution	O
+is	O
+added	O
+dropwise	O
+to	O
+a	O
+stirred	O
+solution	O
+of	O
+1	O
+%	O
+triethylamine	O
+in	O
+hexane	O
+.	O
+
+The	O
+resulting	O
+precipitate	O
+is	O
+
+collected	O
+via	O
+filtration	O
+on	O
+a	O
+sintered	O
+glass	O
+filter	O
+,	O
+washed	O
+with	O
+hexane	O
+and	O
+dried	O
+in	O
+a	O
+vacuum	O
+desiccator	O
+.	O
+
+Removal	O
+of	O
+Base	O
+Protecting	O
+Groups	O
+with	O
+Ethylenediamine	O
+.	O
+
+Several	O
+mg	O
+of	O
+
+d	O
+-	O
+I	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzA	O
+,	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzC	O
+and	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ibu	O
+G	O
+were	O
+each	O
+dissolved	O
+in	O
+250	O
+pl	O
+of	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+.	O
+
+The	O
+solutions	O
+were	O
+incubated	O
+at	O
+room	O
+temperature	O
+.	O
+
+At	O
+various	O
+times	O
+aliquots	O
+were	O
+chromatographed	O
+on	O
+silica	O
+gel	O
+TLC	O
+plates	O
+which	O
+were	O
+eluted	O
+with	O
+10	O
+%	O
+methanol	O
+in	O
+chloroform	O
+.	O
+
+The	O
+spots	O
+corresponding	O
+to	O
+the	O
+starting	O
+material	O
+and	O
+the	O
+product	O
+were	O
+cut	O
+out	O
+and	O
+
+treated	O
+with	O
+1	O
+.	O
+5	O
+ml	O
+of	O
+perchloric	O
+acid	O
+/	O
+ethanol	O
+(	O
+3	O
+:	O
+2	O
+,	O
+v	O
+/	O
+v	O
+)	O
+for	O
+30	O
+min	O
+.	O
+
+The	O
+
+absorbance	O
+of	O
+each	O
+solution	O
+was	O
+measured	O
+at	O
+500	O
+nm	O
+and	O
+the	O
+percent	O
+reaction	O
+was	O
+determined	O
+.	O
+
+The	O
+half	O
+-	O
+lives	O
+of	O
+the	O
+reactions	O
+are	O
+given	O
+in	O
+Table	O
+II	O
+.	O
+
+Removal	O
+of	O
+Protected	O
+-	O
+Nucleosides	O
+from	O
+Polystyrene	O
+Support	O
+.	O
+
+Five	O
+mg	O
+of	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+T	O
+(	O
+ED	O
+(	O
+1	O
+%	O
+crosslinked	O
+)	O
+,	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzA	O
+O	O
+?	O
+(	O
+1	O
+%	O
+crosslinked	O
+)	O
+,	O
+
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzC	O
+(	O
+?	O
+)	O
+(	O
+1	O
+%	O
+and	O
+2	O
+%	O
+crosslinked	O
+)	O
+and	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ibuGcD	O
+(	O
+1	O
+%	O
+and	O
+2	O
+%	O
+crosslinked	O
+)	O
+were	O
+each	O
+treated	O
+with	O
+500	O
+ul	O
+of	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+solution	O
+at	O
+room	O
+temperature	O
+.	O
+
+At	O
+various	O
+times	O
+,	O
+10	O
+pl	O
+aliquots	O
+were	O
+
+removed	O
+,	O
+the	O
+solvent	O
+was	O
+evaporated	O
+and	O
+the	O
+residue	O
+was	O
+dissolved	O
+in	O
+1	O
+ml	O
+of	O
+perchloric	O
+acid	O
+/	O
+ethanol	O
+solution	O
+(	O
+3	O
+:	O
+2	O
+,	O
+v	O
+/	O
+v	O
+)	O
+.	O
+
+The	O
+amount	O
+of	O
+dimethoxytrityl	O
+cation	O
+and	O
+hence	O
+the	O
+amount	O
+of	O
+nucleoside	O
+cleaved	O
+from	O
+the	O
+support	O
+was	O
+
+determined	O
+by	O
+measuring	O
+the	O
+absorbance	O
+at	O
+500	O
+nm	O
+.	O
+
+The	O
+half	O
+lives	O
+of	O
+the	O
+cleavage	O
+reactions	O
+are	O
+given	O
+in	O
+Table	O
+II	O
+.	O
+
+Hydrolysis	O
+of	O
+the	O
+Methylphosphonate	O
+Linkage	O
+by	O
+Ethylenediamine	O
+.	O
+
+Oligonucleoside	O
+methylphosphonates	O
+(	O
+1	O
+.	O
+25	O
+A254	O
+units	O
+each	O
+)	O
+were	O
+treated	O
+with	O
+50	O
+il	O
+of	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+at	O
+room	O
+temperature	O
+.	O
+
+Aliquots	O
+
+6230	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+(	O
+10	O
+pl	O
+)	O
+were	O
+withdrawn	O
+at	O
+various	O
+times	O
+and	O
+the	O
+solvents	O
+were	O
+evaporated	O
+.	O
+
+The	O
+residue	O
+was	O
+dissolved	O
+in	O
+20	O
+PI	O
+of	O
+50	O
+%	O
+aqueous	O
+ethanol	O
+and	O
+the	O
+solution	O
+
+examined	O
+by	O
+C	O
+-	O
+18	O
+reversed	O
+phase	O
+HPLC	O
+using	O
+a	O
+0	O
+%	O
+to	O
+25	O
+%	O
+acetonitrile	O
+in	O
+water	O
+gradient	O
+.	O
+
+The	O
+mole	O
+percent	O
+of	O
+starting	O
+oligomer	O
+remaining	O
+after	O
+100	O
+hrs	O
+of	O
+treatment	O
+is	O
+given	O
+in	O
+Table	O
+III	O
+.	O
+
+Hydrolysis	O
+of	O
+Oligonucleoside	O
+Methylphosphonates	O
+in	O
+Acid	O
+.	O
+
+Six	O
+A254	O
+units	O
+of	O
+oligomer	O
+were	O
+dissolved	O
+in	O
+100	O
+pl	O
+of	O
+0	O
+.	O
+01	O
+M	O
+hydrochloric	O
+acid	O
+solution	O
+.	O
+
+The	O
+
+solution	O
+was	O
+heated	O
+at	O
+either	O
+450	O
+or	O
+650C	O
+.	O
+
+Aliquots	O
+(	O
+10	O
+Pil	O
+)	O
+were	O
+withdrawn	O
+at	O
+various	O
+times	O
+and	O
+added	O
+to	O
+10	O
+pl	O
+of	O
+0	O
+.	O
+015	O
+M	O
+ammonium	O
+hydroxide	O
+at	O
+0	O
+?	O
+C	O
+.	O
+
+The	O
+samples	O
+were	O
+then	O
+injected	O
+directly	O
+onto	O
+a	O
+C	O
+-	O
+18	O
+reversed	O
+phase	O
+column	O
+which	O
+
+was	O
+eluted	O
+with	O
+50	O
+ml	O
+of	O
+a	O
+linear	O
+gradient	O
+of	O
+0	O
+%	O
+to	O
+25	O
+%	O
+acetonitrile	O
+in	O
+water	O
+
+at	O
+a	O
+flow	O
+rate	O
+of	O
+2	O
+.	O
+5	O
+ml	O
+/	O
+min	O
+.	O
+
+The	O
+products	O
+of	O
+the	O
+reaction	O
+were	O
+determined	O
+by	O
+comparison	O
+with	O
+authentic	O
+samples	O
+.	O
+
+Labeling	O
+5	O
+'	O
+-	O
+End	O
+of	O
+Oligonucleoside	O
+Methylphosphonates	O
+with	O
+T4	O
+-	O
+Polynucleotide	O
+Kinase	O
+.	O
+
+Oligonucleoside	O
+methylphosphonates	O
+(	O
+2	O
+nmol	O
+)	O
+were	O
+dissolved	O
+in	O
+a	O
+buffer	O
+solution	O
+containing	O
+50	O
+mM	O
+Tris	O
+-	O
+HC1	O
+(	O
+pH	O
+9	O
+.	O
+0	O
+)	O
+,	O
+10	O
+mM	O
+MgCl2	O
+,	O
+5	O
+mM	O
+dithiothreitol	O
+,	O
+20	O
+pM	O
+spermidine	O
+,	O
+and	O
+[	O
+y	O
+-	O
+32P	O
+]	O
+ATP	O
+(	O
+8	O
+ljCi	O
+,	O
+4Ci	O
+/	O
+mmol	O
+)	O
+.	O
+
+T4	O
+-	O
+polynucleotide	O
+kinase	O
+(	O
+4	O
+units	O
+)	O
+was	O
+added	O
+to	O
+the	O
+solution	O
+,	O
+which	O
+was	O
+made	O
+up	O
+to	O
+50	O
+ul	O
+by	O
+adding	O
+water	O
+.	O
+
+The	O
+solutions	O
+were	O
+incubated	O
+at	O
+370C	O
+for	O
+2	O
+hrs	O
+.	O
+
+The	O
+reaction	O
+was	O
+checked	O
+by	O
+PEI	O
+-	O
+cellulose	O
+TLC	O
+.	O
+
+The	O
+PEI	O
+-	O
+cellulose	O
+plate	O
+
+(	O
+12x2Ocm	O
+,	O
+Merck	O
+)	O
+was	O
+preactivated	O
+by	O
+elution	O
+with	O
+1	O
+.	O
+2	O
+M	O
+pyridinium	O
+formate	O
+(	O
+pH	O
+3	O
+.	O
+5	O
+)	O
+.	O
+
+Small	O
+aliquots	O
+(	O
+0	O
+.	O
+1	O
+pl	O
+)	O
+of	O
+PNK	O
+reaction	O
+solutions	O
+were	O
+applied	O
+and	O
+
+developed	O
+with	O
+1	O
+.	O
+5	O
+M	O
+pyridinium	O
+formate	O
+(	O
+pH	O
+3	O
+.	O
+5	O
+)	O
+.	O
+
+The	O
+TLC	O
+plate	O
+was	O
+dried	O
+and	O
+autoradiographed	O
+using	O
+an	O
+intensifying	O
+screen	O
+at	O
+room	O
+temperature	O
+.	O
+
+Gel	O
+Electrophoresis	O
+of	O
+5	O
+'	O
+-	O
+Labeled	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+Polyacrylamide	O
+gels	O
+were	O
+prepared	O
+by	O
+polymerizing	O
+a	O
+solution	O
+containing	O
+18	O
+%	O
+(	O
+w	O
+/	O
+v	O
+)	O
+acrylamide	O
+,	O
+0	O
+.	O
+8	O
+%	O
+(	O
+w	O
+/	O
+v	O
+)	O
+N	O
+,	O
+N	O
+'	O
+-	O
+methylenebisacrylami	O
+.	O
+
+7M	O
+urea	O
+,	O
+89	O
+mM	O
+Tris	O
+-	O
+borate	O
+(	O
+pH	O
+8	O
+.	O
+2	O
+)	O
+,	O
+2	O
+mM	O
+EDTA	O
+,	O
+0	O
+.	O
+07	O
+%	O
+(	O
+w	O
+/	O
+v	O
+)	O
+ammonium	O
+persulfate	O
+,	O
+in	O
+the	O
+
+presence	O
+of	O
+N	O
+,	O
+N	O
+,	O
+N	O
+'	O
+,	O
+N	O
+'	O
+-	O
+tetramethylethylened	O
+(	O
+20	O
+Pil	O
+/	O
+20	O
+ml	O
+solution	O
+)	O
+.	O
+
+The	O
+
+solution	O
+was	O
+poured	O
+into	O
+a	O
+0	O
+.	O
+75	O
+x	O
+140	O
+x	O
+150	O
+mm	O
+mold	O
+and	O
+allowed	O
+to	O
+polymerize	O
+for	O
+2	O
+hrs	O
+at	O
+room	O
+temperature	O
+.	O
+
+5	O
+'	O
+-	O
+Labeled	O
+oligonucleoside	O
+methylphosphonates	O
+were	O
+dissolved	O
+in	O
+10	O
+%	O
+aqueous	O
+glycerol	O
+solution	O
+containing	O
+0	O
+.	O
+04	O
+%	O
+bromophenol	O
+blue	O
+and	O
+applied	O
+to	O
+the	O
+gel	O
+.	O
+
+The	O
+electrophoresis	O
+was	O
+run	O
+using	O
+89	O
+mM	O
+
+Tris	O
+-	O
+Borate	O
+buffer	O
+containing	O
+10	O
+mM	O
+EDTA	O
+.	O
+
+After	O
+electrophoresis	O
+the	O
+gel	O
+was	O
+dried	O
+using	O
+a	O
+gel	O
+-	O
+dryer	O
+and	O
+autoradiographed	O
+using	O
+intensifying	O
+screens	O
+at	O
+room	O
+temperature	O
+.	O
+
+Pa	O
+rti	O
+al	O
+Cl	O
+eavage	O
+of	O
+01	O
+i	O
+gonucl	O
+eosi	O
+de	O
+Methyl	O
+phosphonates	O
+wi	O
+th	O
+Hydrochl	O
+ori	O
+c	O
+Aci	O
+d	O
+or	O
+Piperidine	O
+.	O
+
+Aliquots	O
+(	O
+1	O
+,	O
+jl	O
+)	O
+from	O
+the	O
+polynucleotide	O
+kinase	O
+reaction	O
+
+6231	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+mixture	O
+were	O
+incubated	O
+with	O
+1	O
+il	O
+of	O
+1	O
+M	O
+hydrochloric	O
+acid	O
+at	O
+37	O
+?	O
+C	O
+for	O
+30	O
+min	O
+.	O
+
+After	O
+incubation	O
+the	O
+solution	O
+was	O
+neutralized	O
+with	O
+1	O
+Pl	O
+of	O
+1	O
+M	O
+ammonium	O
+
+hydroxide	O
+and	O
+then	O
+allowed	O
+to	O
+stand	O
+at	O
+room	O
+temperature	O
+for	O
+10	O
+min	O
+before	O
+cooling	O
+to	O
+00	O
+.	O
+
+Alternatively	O
+,	O
+aliquots	O
+(	O
+1	O
+pl	O
+)	O
+from	O
+the	O
+phosphorylation	O
+
+reaction	O
+were	O
+incubated	O
+with	O
+1	O
+ul	O
+of	O
+1	O
+M	O
+aqueous	O
+piperidine	O
+at	O
+370C	O
+for	O
+10	O
+min	O
+after	O
+which	O
+the	O
+solution	O
+was	O
+cooled	O
+to	O
+0	O
+?	O
+and	O
+evaporated	O
+.	O
+
+The	O
+treated	O
+
+samples	O
+were	O
+then	O
+subjected	O
+to	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+as	O
+described	O
+above	O
+without	O
+further	O
+purification	O
+.	O
+
+RESULTS	O
+AND	O
+DISCUSSION	O
+
+Synthesis	O
+of	O
+Protected	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+Table	O
+I	O
+shows	O
+some	O
+of	O
+the	O
+protected	O
+oligonucleoside	O
+methylphosphonates	O
+which	O
+have	O
+been	O
+
+synthesized	O
+on	O
+aminomethyl	O
+succinyl	O
+-	O
+derivatized	O
+polystyrene	O
+supports	O
+.	O
+
+The	O
+basic	O
+synthetic	O
+steps	O
+which	O
+are	O
+shown	O
+in	O
+Figure	O
+1	O
+are	O
+described	O
+in	O
+detail	O
+in	O
+the	O
+Experimental	O
+section	O
+.	O
+
+These	O
+steps	O
+are	O
+:	O
+(	O
+1	O
+)	O
+removal	O
+of	O
+the	O
+
+dimethoxytrityl	O
+group	O
+with	O
+1	O
+M	O
+zinc	O
+bromide	O
+solution	O
+;	O
+(	O
+2	O
+)	O
+drying	O
+the	O
+support	O
+
+via	O
+co	O
+-	O
+evaporation	O
+with	O
+anhydrous	O
+pyridine	O
+;	O
+(	O
+3	O
+)	O
+reaction	O
+of	O
+the	O
+support	O
+-	O
+bound	O
+
+nucleoside	O
+or	O
+oligonucleotide	O
+with	O
+a	O
+coupling	O
+mixture	O
+containing	O
+0	O
+.	O
+15	O
+to	O
+0	O
+.	O
+2	O
+M	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+)	O
+-	O
+NpjEt3NH	O
+and	O
+0	O
+.	O
+3	O
+to	O
+0	O
+.	O
+6	O
+M	O
+mesitylenesulfonyl	O
+-	O
+3	O
+-	O
+nitrotriazole	O
+in	O
+anhydrous	O
+pyridine	O
+and	O
+(	O
+4	O
+)	O
+acetylation	O
+of	O
+unreacted	O
+5	O
+'	O
+-	O
+OH	O
+groups	O
+with	O
+acetic	O
+
+anhydride	O
+.	O
+
+The	O
+reactions	O
+and	O
+washing	O
+steps	O
+were	O
+most	O
+conveniently	O
+carried	O
+out	O
+in	O
+a	O
+polypropylene	O
+Econo	O
+Column	O
+fitted	O
+with	O
+a	O
+septum	O
+cap	O
+and	O
+a	O
+3	O
+-	O
+way	O
+Teflon	O
+
+DMTrO	O
+,	O
+O	O
+Figure	O
+1	O
+:	O
+Preparation	O
+of	O
+Protected	O
+
+Oligonucleoside	O
+Methylphosphonates	O
+on	O
+a	O
+1	O
+T	O
+o	O
+w	O
+Polystyrene	O
+Support	O
+
+0	O
+
+H	O
+BFvON	O
+DlDTrOjO4B	O
+
+U	O
+)	O
+I	O
+CH3	O
+-	O
+gd	O
+-	O
+OEt	O
+3NH	O
+
+0	O
+
+6232	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+stopcock	O
+.	O
+
+Thus	O
+no	O
+transfers	O
+of	O
+the	O
+support	O
+are	O
+required	O
+using	O
+this	O
+apparatus	O
+.	O
+
+The	O
+synthetic	O
+procedure	O
+is	O
+analogous	O
+to	O
+the	O
+phosphotriester	O
+approach	O
+used	O
+to	O
+prepared	O
+protected	O
+oligonucleotide	O
+phosphotriesters	O
+on	O
+polystyrene	O
+supports	O
+(	O
+6	O
+)	O
+.	O
+
+However	O
+,	O
+we	O
+found	O
+the	O
+methylphosrhonate	O
+coupling	O
+reaction	O
+to	O
+be	O
+
+extremely	O
+sensitive	O
+to	O
+moisture	O
+.	O
+
+Drying	O
+procedures	O
+such	O
+as	O
+washing	O
+with	O
+
+anhydrous	O
+solvent	O
+or	O
+blowing	O
+dry	O
+nitrogen	O
+gas	O
+through	O
+the	O
+support	O
+which	O
+are	O
+satisfactory	O
+for	O
+phosphotriester	O
+synthesis	O
+resulted	O
+in	O
+low	O
+yields	O
+of	O
+the	O
+methylphosphonates	O
+.	O
+
+The	O
+best	O
+yields	O
+were	O
+obtained	O
+when	O
+the	O
+support	O
+was	O
+
+co	O
+-	O
+evaporated	O
+with	O
+anhydrous	O
+pyridine	O
+by	O
+directly	O
+attaching	O
+the	O
+reaction	O
+
+column	O
+to	O
+a	O
+vacuum	O
+pump	O
+and	O
+dry	O
+-	O
+ice	O
+trap	O
+.	O
+
+Three	O
+10	O
+min	O
+co	O
+-	O
+evaporations	O
+were	O
+sufficient	O
+to	O
+render	O
+the	O
+support	O
+anhydrous	O
+.	O
+
+The	O
+protected	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphonate	O
+triethylammonium	O
+salts	O
+used	O
+in	O
+the	O
+coupling	O
+reactions	O
+were	O
+prepared	O
+from	O
+their	O
+cyanoethyl	O
+ester	O
+
+derivatives	O
+(	O
+3	O
+)	O
+.	O
+
+These	O
+monomers	O
+were	O
+recovered	O
+after	O
+each	O
+coupling	O
+step	O
+and	O
+
+were	O
+freed	O
+of	O
+unreacted	O
+MSNT	O
+by	O
+a	O
+simple	O
+extraction	O
+step	O
+.	O
+
+After	O
+precipitation	O
+and	O
+drying	O
+,	O
+the	O
+monomers	O
+could	O
+be	O
+reused	O
+for	O
+other	O
+syntheses	O
+.	O
+
+The	O
+ability	O
+to	O
+recover	O
+the	O
+unreacted	O
+monomers	O
+is	O
+particularly	O
+important	O
+for	O
+large	O
+scale	O
+
+synthesis	O
+since	O
+large	O
+excesses	O
+of	O
+these	O
+materials	O
+are	O
+employed	O
+in	O
+the	O
+coupling	O
+step	O
+.	O
+
+This	O
+recovery	O
+step	O
+represents	O
+a	O
+potential	O
+advantage	O
+over	O
+the	O
+phosphine	O
+synthetic	O
+method	O
+(	O
+4	O
+)	O
+,	O
+since	O
+it	O
+is	O
+not	O
+clear	O
+that	O
+nucleoside	O
+3	O
+'	O
+-	O
+methylphosphine	O
+chlorides	O
+can	O
+be	O
+recovered	O
+after	O
+reaction	O
+.	O
+
+Two	O
+types	O
+of	O
+methylphosphonate	O
+oligomers	O
+were	O
+prepared	O
+;	O
+those	O
+which	O
+contain	O
+only	O
+methylphosphonate	O
+linkages	O
+,	O
+oligomers	O
+1	O
+-	O
+6	O
+,	O
+and	O
+those	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+-	O
+nucleoside	O
+3	O
+'	O
+-	O
+p	O
+-	O
+chlorophenyl	O
+phosphotriester	O
+moiety	O
+,	O
+
+oligomers	O
+7	O
+-	O
+10	O
+.	O
+
+Oligomers	O
+were	O
+synthesized	O
+on	O
+both	O
+1	O
+%	O
+and	O
+2	O
+%	O
+crosslinked	O
+
+supports	O
+.	O
+
+As	O
+shown	O
+in	O
+Table	O
+I	O
+,	O
+the	O
+average	O
+yield	O
+per	O
+coupling	O
+step	O
+which	O
+was	O
+determined	O
+by	O
+trityl	O
+group	O
+analysis	O
+was	O
+approximately	O
+82	O
+%	O
+,	O
+for	O
+both	O
+types	O
+of	O
+
+support	O
+.	O
+
+This	O
+yield	O
+is	O
+adequate	O
+to	O
+allow	O
+preparation	O
+of	O
+protected	O
+octamers	O
+or	O
+nonamers	O
+in	O
+25	O
+%	O
+and	O
+20	O
+%	O
+overall	O
+yield	O
+,	O
+respectively	O
+.	O
+
+Deprotection	O
+.	O
+
+Our	O
+previous	O
+studies	O
+(	O
+1	O
+)	O
+and	O
+those	O
+of	O
+Sinha	O
+et	O
+al	O
+.	O
+
+(	O
+4	O
+)	O
+show	O
+
+that	O
+methylphosphonate	O
+linkages	O
+are	O
+cleaved	O
+by	O
+base	O
+.	O
+
+We	O
+found	O
+this	O
+hydrolysis	O
+reaction	O
+to	O
+depend	O
+to	O
+some	O
+extent	O
+upon	O
+the	O
+nucleoside	O
+sequence	O
+of	O
+the	O
+
+oligomer	O
+.	O
+
+Hydrolysis	O
+of	O
+methylphosphonate	O
+linkages	O
+by	O
+concentrated	O
+ammonium	O
+hydroxide	O
+in	O
+pyridine	O
+(	O
+1	O
+:	O
+1	O
+v	O
+/	O
+v	O
+)	O
+,	O
+the	O
+reagent	O
+commonly	O
+used	O
+to	O
+remove	O
+
+oligonucleotide	O
+base	O
+protecting	O
+groups	O
+,	O
+can	O
+be	O
+largely	O
+suppressed	O
+if	O
+the	O
+
+reactions	O
+are	O
+run	O
+at	O
+0	O
+?	O
+C	O
+(	O
+1	O
+)	O
+.	O
+
+However	O
+,	O
+these	O
+conditions	O
+are	O
+unsatisfactory	O
+for	O
+removal	O
+of	O
+oligonucleoside	O
+methylphosphonates	O
+from	O
+the	O
+polystyrene	O
+
+6233	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Table	O
+I	O
+.	O
+Syntheses	O
+of	O
+Protected	O
+Oligonucleoside	O
+Methylphosphonates	O
+on	O
+
+Polystyrene	O
+Supports	O
+
+Support	O
+Average	O
+cross	O
+-	O
+yield	O
+Protected	O
+oligomer	O
+(	O
+a	O
+)	O
+linking	O
+per	O
+
+(	O
+%	O
+)	O
+coupling	O
+
+step	O
+(	O
+%	O
+)	O
+
+1	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzCpbzCpbzApT	O
+-	O
+O	O
+1	O
+81	O
+2	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ibuGpbzCpbzCpbzApT	O
+-	O
+1	O
+82	O
+3	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzCpbzApi	O
+buGpi	O
+buGpTpbzApbzA	O
+-	O
+G1i	O
+2	O
+83	O
+4	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzCLpTpT	O
+bzApbzCpbzCpTpibuG	O
+-	O
+?	O
+
+2	O
+85	O
+5	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+TpbzCpbzCpTpbzCpbzCp	O
+-	O
+(	O
+?	O
+
+2	O
+86	O
+6	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+TpTpTpbzApbzCpbzCpTp	O
+-	O
+?	O
+
+1	O
+83	O
+7	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzApbzApbzA	O
+-	O
+?	O
+
+1	O
+83	O
+8	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzA4bzCpbzCpbzApT	O
+-	O
+?	O
+
+1	O
+81	O
+9	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzApibuGpbzCpbzApbzA	O
+-	O
+(	O
+2	O
+74	O
+10	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+bzApbzApbzApbzApibuG	O
+-	O
+(	O
+Q	O
+1	O
+86	O
+
+(	O
+a	O
+)	O
+p	O
+=	O
+methylphosphonate	O
+linkage	O
+
+T	O
+=	O
+p	O
+-	O
+chlorophenyl	O
+phosphotriester	O
+linkage	O
+(	O
+Q	O
+=	O
+polystyrene	O
+support	O
+
+(	O
+b	O
+)	O
+Determined	O
+by	O
+analysis	O
+of	O
+the	O
+dimethoxytrityl	O
+group	O
+after	O
+each	O
+
+coupling	O
+step	O
+.	O
+
+support	O
+.	O
+
+We	O
+therefore	O
+examined	O
+other	O
+deprotection	O
+procedures	O
+.	O
+
+Recently	O
+Barnett	O
+and	O
+Letsinger	O
+described	O
+removal	O
+of	O
+base	O
+protecting	O
+groups	O
+from	O
+oligonucleotide	O
+B	O
+,	O
+B	O
+,	O
+0	O
+-	O
+trichloroethylphosph	O
+using	O
+a	O
+
+mixture	O
+of	O
+ethylenediamine	O
+in	O
+phenol	O
+(	O
+7	O
+)	O
+.	O
+
+We	O
+have	O
+found	O
+ethylenediamine	O
+in	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+rapidly	O
+and	O
+cleanly	O
+removes	O
+benzoyl	O
+and	O
+isobutyryl	O
+protecting	O
+groups	O
+from	O
+dA	O
+,	O
+dC	O
+and	O
+dG	O
+nucleosides	O
+.	O
+
+This	O
+reagent	O
+is	O
+
+particularly	O
+attractive	O
+since	O
+it	O
+can	O
+be	O
+easily	O
+removed	O
+by	O
+evaporation	O
+.	O
+
+In	O
+our	O
+initial	O
+investigations	O
+,	O
+ol	O
+igonucleoside	O
+methylphosphonates	O
+were	O
+
+cleaved	O
+from	O
+the	O
+support	O
+and	O
+base	O
+protecting	O
+groups	O
+were	O
+removed	O
+by	O
+treatment	O
+with	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+at	O
+65	O
+?	O
+C	O
+for	O
+3	O
+hrs	O
+.	O
+
+Although	O
+
+preliminary	O
+results	O
+indicated	O
+the	O
+methylphosphonate	O
+linkages	O
+of	O
+several	O
+dimers	O
+were	O
+stable	O
+to	O
+these	O
+conditions	O
+,	O
+we	O
+later	O
+found	O
+that	O
+the	O
+linkages	O
+of	O
+onger	O
+
+6234	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Table	O
+II	O
+.	O
+
+Hydrolysis	O
+of	O
+Protected	O
+Nucleosides	O
+by	O
+Ethylenediamine	O
+at	O
+220C	O
+
+Protected	O
+Time	O
+required	O
+to	O
+Time	O
+required	O
+to	O
+nucleoside	O
+remove	O
+50	O
+%	O
+of	O
+the	O
+cleave	O
+50	O
+%	O
+of	O
+the	O
+
+base	O
+protecting	O
+nucleoside	O
+from	O
+the	O
+groups	O
+(	O
+min	O
+)	O
+1	O
+%	O
+crosslinked	O
+
+support	O
+(	O
+min	O
+)	O
+
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+)	O
+bzA	O
+10	O
+105	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+bzC	O
+20	O
+105	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+i	O
+buG	O
+40	O
+54	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+T	O
+_	O
+105	O
+
+oligomers	O
+were	O
+hydrolyzed	O
+to	O
+various	O
+extents	O
+by	O
+this	O
+procedure	O
+.	O
+
+This	O
+of	O
+
+course	O
+resulted	O
+in	O
+loss	O
+of	O
+product	O
+as	O
+was	O
+evidenced	O
+by	O
+the	O
+presence	O
+of	O
+shorter	O
+oligomers	O
+in	O
+amounts	O
+greater	O
+than	O
+expected	O
+based	O
+upon	O
+the	O
+coupling	O
+yields	O
+.	O
+
+To	O
+circumvent	O
+this	O
+problem	O
+we	O
+examined	O
+the	O
+deprotection	O
+reactions	O
+at	O
+lower	O
+temperatures	O
+and	O
+found	O
+they	O
+could	O
+be	O
+run	O
+effectively	O
+at	O
+room	O
+
+temperature	O
+.	O
+
+Table	O
+II	O
+shows	O
+the	O
+half	O
+-	O
+lives	O
+for	O
+removing	O
+the	O
+base	O
+protecting	O
+groups	O
+from	O
+nucleosides	O
+at	O
+room	O
+temperature	O
+.	O
+
+While	O
+the	O
+isobutryl	O
+protecting	O
+group	O
+is	O
+removed	O
+at	O
+the	O
+slowest	O
+rate	O
+,	O
+all	O
+the	O
+groups	O
+are	O
+completely	O
+removed	O
+within	O
+240	O
+min	O
+.	O
+
+The	O
+sole	O
+product	O
+of	O
+each	O
+reaction	O
+is	O
+the	O
+5	O
+'	O
+-	O
+O	O
+-	O
+dimethoxytritylnucle	O
+as	O
+shown	O
+by	O
+TLC	O
+.	O
+
+Table	O
+II	O
+also	O
+shows	O
+the	O
+half	O
+-	O
+lives	O
+for	O
+cleavage	O
+of	O
+protected	O
+nucleosides	O
+from	O
+the	O
+1	O
+%	O
+crosslinked	O
+support	O
+.	O
+
+The	O
+deoxyguanosine	O
+nucleoside	O
+is	O
+cleaved	O
+
+most	O
+rapidly	O
+while	O
+the	O
+other	O
+three	O
+nucleosides	O
+have	O
+essentially	O
+the	O
+same	O
+rates	O
+of	O
+hydrolysis	O
+.	O
+
+All	O
+the	O
+nucleosides	O
+are	O
+completely	O
+removed	O
+from	O
+the	O
+support	O
+within	O
+7	O
+hrs	O
+.	O
+
+In	O
+contrast	O
+,	O
+very	O
+different	O
+rates	O
+were	O
+observed	O
+for	O
+the	O
+2	O
+%	O
+
+crosslinked	O
+supports	O
+.	O
+
+In	O
+these	O
+cases	O
+,	O
+very	O
+little	O
+cleavage	O
+occurred	O
+during	O
+the	O
+first	O
+4	O
+hrs	O
+of	O
+incubation	O
+after	O
+which	O
+increasing	O
+amounts	O
+of	O
+nucleoside	O
+were	O
+released	O
+over	O
+a	O
+24	O
+hr	O
+period	O
+.	O
+
+This	O
+effect	O
+may	O
+be	O
+due	O
+to	O
+the	O
+slower	O
+swelling	O
+rate	O
+of	O
+the	O
+2	O
+%	O
+crosslinked	O
+support	O
+versus	O
+the	O
+1	O
+%	O
+support	O
+.	O
+
+The	O
+
+results	O
+of	O
+these	O
+experiments	O
+suggest	O
+that	O
+,	O
+although	O
+condensation	O
+reactions	O
+
+occur	O
+with	O
+equal	O
+efficiencies	O
+on	O
+both	O
+the	O
+1	O
+%	O
+and	O
+2	O
+%	O
+crosslinked	O
+supports	O
+,	O
+the	O
+1	O
+%	O
+support	O
+is	O
+preferred	O
+for	O
+syntheses	O
+since	O
+the	O
+oligomers	O
+can	O
+be	O
+removed	O
+more	O
+readily	O
+under	O
+mild	O
+conditions	O
+.	O
+
+The	O
+stability	O
+of	O
+the	O
+methylphosphonate	O
+linkage	O
+in	O
+a	O
+number	O
+of	O
+oligomers	O
+
+of	O
+varying	O
+chain	O
+length	O
+and	O
+base	O
+composition	O
+was	O
+examined	O
+following	O
+prolonged	O
+exposure	O
+to	O
+ethylenediamine	O
+/	O
+ethanol	O
+at	O
+room	O
+temperature	O
+.	O
+
+As	O
+shown	O
+in	O
+Table	O
+III	O
+,	O
+some	O
+of	O
+these	O
+oligomers	O
+,	O
+most	O
+notably	O
+the	O
+dimer	O
+and	O
+d	O
+-	O
+GpGpT	O
+,	O
+were	O
+
+6235	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Table	O
+III	O
+.	O
+
+Hydrolysis	O
+of	O
+Oligonucleoside	O
+Methylphosphonates	O
+by	O
+
+Ethylenediamine	O
+at	O
+22	O
+?	O
+C	O
+
+|	O
+Oligomer	O
+Mole	O
+percent	O
+of	O
+oligomer	O
+remaining	O
+after	O
+treatment	O
+for	O
+
+24	O
+hrs	O
+48	O
+hrs	O
+96	O
+hrs	O
+
+d	O
+-	O
+T	O
+A	O
+100	O
+100	O
+100	O
+d	O
+-	O
+A5r	O
+100	O
+100	O
+100	O
+d	O
+-	O
+TpT	O
+100	O
+100	O
+100	O
+d	O
+-	O
+l	O
+pT	O
+95	O
+97	O
+91	O
+d	O
+-	O
+qgG	O
+{	O
+T	O
+100	O
+100	O
+100	O
+d	O
+-	O
+ApApA	O
+93	O
+87	O
+75	O
+d	O
+-	O
+C	O
+pC	O
+ApT	O
+92	O
+83	O
+67	O
+
+completely	O
+stable	O
+over	O
+a	O
+96	O
+hr	O
+period	O
+.	O
+
+The	O
+maximum	O
+rate	O
+of	O
+hydrolysis	O
+for	O
+a	O
+methylphosphonate	O
+linkage	O
+in	O
+those	O
+oligomers	O
+which	O
+were	O
+hydrolyzed	O
+is	O
+
+estimated	O
+to	O
+be	O
+0	O
+.	O
+13	O
+mole	O
+%	O
+/	O
+hr	O
+.	O
+
+The	O
+results	O
+of	O
+these	O
+studies	O
+show	O
+that	O
+the	O
+oligonucleoside	O
+methylphosphonates	O
+could	O
+be	O
+cleaved	O
+from	O
+the	O
+1	O
+%	O
+crosslinked	O
+support	O
+and	O
+completely	O
+freed	O
+of	O
+base	O
+protecting	O
+groups	O
+with	O
+little	O
+or	O
+no	O
+hydrolysis	O
+of	O
+the	O
+methylphosphonate	O
+linkage	O
+by	O
+treatment	O
+with	O
+
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+at	O
+room	O
+temperature	O
+for	O
+7	O
+hrs	O
+.	O
+
+These	O
+conditions	O
+were	O
+subsequently	O
+adopted	O
+for	O
+the	O
+deprotection	O
+step	O
+.	O
+
+Purification	O
+of	O
+Oligonucleoside	O
+Methylphosphonates	O
+.	O
+
+Two	O
+methods	O
+were	O
+employed	O
+to	O
+purify	O
+oligomers	O
+following	O
+cleavage	O
+from	O
+the	O
+support	O
+.	O
+
+For	O
+oligomers	O
+which	O
+contain	O
+only	O
+methylphosphonate	O
+linkages	O
+,	O
+the	O
+tritylated	O
+oligomer	O
+was	O
+isolated	O
+
+by	O
+preparative	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+This	O
+separation	O
+is	O
+based	O
+upon	O
+the	O
+greater	O
+affinity	O
+of	O
+the	O
+tritylated	O
+oligomer	O
+for	O
+the	O
+hydrophobic	O
+C	O
+-	O
+18	O
+matrix	O
+of	O
+the	O
+
+column	O
+.	O
+
+Shorter	O
+,	O
+non	O
+-	O
+tritylated	O
+oligomers	O
+were	O
+first	O
+eluted	O
+with	O
+a	O
+0	O
+%	O
+to	O
+25	O
+%	O
+or	O
+0	O
+%	O
+to	O
+30	O
+%	O
+acetonitrile	O
+in	O
+water	O
+gradient	O
+.	O
+
+The	O
+tritylated	O
+product	O
+was	O
+then	O
+eluted	O
+with	O
+a	O
+step	O
+gradient	O
+of	O
+50	O
+%	O
+acetonitrile	O
+in	O
+water	O
+.	O
+
+The	O
+dimethoxytrityl	O
+group	O
+was	O
+removed	O
+from	O
+the	O
+material	O
+in	O
+the	O
+50	O
+%	O
+
+acetonitrile	O
+fraction	O
+by	O
+treatment	O
+with	O
+80	O
+%	O
+acetic	O
+acid	O
+at	O
+room	O
+temperature	O
+.	O
+
+Because	O
+these	O
+oligomers	O
+were	O
+originally	O
+cleaved	O
+from	O
+the	O
+support	O
+by	O
+
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+at	O
+65	O
+?	O
+C	O
+,	O
+we	O
+usually	O
+found	O
+that	O
+the	O
+
+tritylated	O
+oligomer	O
+fraction	O
+contained	O
+shorter	O
+oligomers	O
+in	O
+addition	O
+to	O
+the	O
+desired	O
+product	O
+.	O
+
+These	O
+were	O
+easily	O
+separated	O
+by	O
+preparative	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+While	O
+this	O
+purification	O
+procedure	O
+is	O
+qualitatively	O
+satisfactory	O
+,	O
+
+recoveries	O
+from	O
+the	O
+reversed	O
+phase	O
+columns	O
+varied	O
+from	O
+50	O
+%	O
+to	O
+90	O
+%	O
+.	O
+
+These	O
+
+losses	O
+which	O
+appeared	O
+to	O
+be	O
+due	O
+to	O
+irreverisble	O
+absorption	O
+of	O
+the	O
+oligomers	O
+to	O
+the	O
+column	O
+varied	O
+depending	O
+on	O
+the	O
+base	O
+composition	O
+of	O
+the	O
+oligomers	O
+.	O
+
+6236	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Figure	O
+2	O
+:	O
+Purification	O
+of	O
+
+d	O
+-	O
+ApApApApGpCpApApG	O
+.	O
+
+(	O
+a	O
+)	O
+Ol	O
+igomers	O
+obtained	O
+after	O
+treatment	O
+of	O
+support	O
+wi	O
+th	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+
+v	O
+/	O
+v	O
+)	O
+.	O
+
+(	O
+b	O
+)	O
+Ol	O
+igomers	O
+obtained	O
+after	O
+treatment	O
+of	O
+the	O
+mixture	O
+in	O
+(	O
+a	O
+)	O
+with	O
+80	O
+%	O
+acetic	O
+acid	O
+.	O
+
+(	O
+c	O
+)	O
+Oligomers	O
+eluted	O
+from	O
+DEAE	O
+cellulose	O
+column	O
+with	O
+
+0	O
+.	O
+15	O
+M	O
+triethylammonium	O
+bicarbonate	O
+.	O
+
+(	O
+d	O
+)	O
+Nonamer	O
+obtained	O
+after	O
+preparative	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+Peaks	O
+marked	O
+
+with	O
+the	O
+symbol	O
+(	O
+X	O
+)	O
+are	O
+derived	O
+from	O
+impurities	O
+in	O
+the	O
+solvents	O
+used	O
+to	O
+elute	O
+the	O
+oligomer	O
+from	O
+the	O
+polystyrene	O
+support	O
+.	O
+
+d	O
+"	O
+AAAGCAAGc	O
+
+O	O
+I	O
+t10	O
+15	O
+20	O
+25	O
+
+Time	O
+(	O
+min	O
+)	O
+
+For	O
+the	O
+oligomers	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+-	O
+nucleoside	O
+phosphotriester	O
+group	O
+,	O
+the	O
+support	O
+was	O
+first	O
+treated	O
+for	O
+40	O
+hrs	O
+with	O
+tetra	O
+-	O
+n	O
+-	O
+butylammonium	O
+
+fluoride	O
+(	O
+8	O
+)	O
+to	O
+remove	O
+the	O
+p	O
+-	O
+chlorophenyl	O
+protecting	O
+group	O
+.	O
+
+These	O
+oligomers	O
+
+6237	O
+
+b	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+were	O
+then	O
+cleaved	O
+from	O
+the	O
+support	O
+and	O
+the	O
+base	O
+protecting	O
+groups	O
+were	O
+removed	O
+by	O
+treatment	O
+with	O
+ethylenediamine	O
+/	O
+ethanol	O
+(	O
+1	O
+:	O
+1	O
+,	O
+v	O
+/	O
+v	O
+)	O
+for	O
+7	O
+hrs	O
+at	O
+room	O
+temperature	O
+.	O
+
+For	O
+example	O
+,	O
+the	O
+reversed	O
+phase	O
+HPLC	O
+profile	O
+for	O
+products	O
+
+obtained	O
+after	O
+cleavage	O
+of	O
+the	O
+nonamer	O
+,	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+ApAjApApGpCpApApG	O
+,	O
+is	O
+shown	O
+in	O
+Figure	O
+2a	O
+.	O
+
+The	O
+peaks	O
+marked	O
+with	O
+(	O
+X	O
+)	O
+are	O
+from	O
+impurities	O
+in	O
+the	O
+
+solvents	O
+used	O
+to	O
+elute	O
+the	O
+oligomer	O
+from	O
+the	O
+support	O
+.	O
+
+The	O
+tritylated	O
+nonamer	O
+appears	O
+at	O
+22	O
+min	O
+in	O
+the	O
+chromatogram	O
+and	O
+is	O
+eluted	O
+with	O
+50	O
+%	O
+aqueous	O
+
+acetonitrile	O
+.	O
+
+After	O
+removal	O
+of	O
+the	O
+dimethoxytrityl	O
+group	O
+,	O
+the	O
+nonamer	O
+elutes	O
+at	O
+15	O
+.	O
+2	O
+min	O
+(	O
+Figure	O
+2b	O
+)	O
+.	O
+
+The	O
+peaks	O
+which	O
+appear	O
+between	O
+19	O
+and	O
+25	O
+min	O
+are	O
+shorter	O
+oligomers	O
+which	O
+contain	O
+a	O
+5	O
+'	O
+-	O
+mesitylenesulfonate	O
+group	O
+.	O
+
+At	O
+this	O
+stage	O
+,	O
+the	O
+nonamer	O
+was	O
+partially	O
+purified	O
+by	O
+ion	O
+exchange	O
+
+chromatography	O
+on	O
+a	O
+DEAE	O
+cellulose	O
+column	O
+.	O
+
+This	O
+step	O
+,	O
+which	O
+resulted	O
+in	O
+84	O
+%	O
+recovery	O
+of	O
+material	O
+loaded	O
+onto	O
+the	O
+column	O
+,	O
+removed	O
+most	O
+of	O
+the	O
+shorter	O
+
+oligomers	O
+as	O
+shown	O
+in	O
+Figure	O
+2c	O
+.	O
+
+After	O
+removal	O
+of	O
+the	O
+buffer	O
+,	O
+the	O
+nonamer	O
+was	O
+purified	O
+by	O
+preparative	O
+reversed	O
+phase	O
+HPLC	O
+using	O
+a	O
+0	O
+%	O
+to	O
+30	O
+%	O
+acetonitrile	O
+in	O
+0	O
+.	O
+1	O
+M	O
+ammonium	O
+acetate	O
+gradient	O
+.	O
+
+The	O
+recovery	O
+of	O
+material	O
+from	O
+the	O
+column	O
+
+(	O
+84	O
+%	O
+)	O
+appears	O
+to	O
+be	O
+higher	O
+when	O
+ammonium	O
+acetate	O
+is	O
+used	O
+.	O
+
+The	O
+pure	O
+nonamer	O
+
+(	O
+Figure	O
+2d	O
+)	O
+was	O
+obtained	O
+in	O
+10	O
+%	O
+overall	O
+yield	O
+based	O
+on	O
+the	O
+amount	O
+of	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2	O
+Tr	O
+]	O
+ibuG	O
+originally	O
+bound	O
+to	O
+the	O
+polystyrene	O
+support	O
+.	O
+
+The	O
+oligomer	O
+was	O
+desalted	O
+on	O
+a	O
+Bio	O
+-	O
+Gel	O
+P	O
+-	O
+2	O
+gel	O
+filtration	O
+column	O
+.	O
+
+Similar	O
+results	O
+were	O
+
+obtained	O
+for	O
+the	O
+other	O
+oligomers	O
+purified	O
+by	O
+this	O
+method	O
+.	O
+
+Thus	O
+,	O
+for	O
+example	O
+dApApA	O
+and	O
+d	O
+-	O
+ApCpCpApT	O
+were	O
+obtained	O
+in	O
+44	O
+%	O
+and	O
+22	O
+%	O
+isolated	O
+yields	O
+respectively	O
+based	O
+upon	O
+the	O
+amount	O
+of	O
+d	O
+-	O
+[	O
+(	O
+MeO	O
+)	O
+2Tr	O
+]	O
+N	O
+.	O
+
+The	O
+5	O
+'	O
+-	O
+terminal	O
+nucleotide	O
+may	O
+be	O
+removed	O
+enzynatically	O
+to	O
+give	O
+an	O
+
+oligomer	O
+which	O
+contains	O
+only	O
+methylphosphonate	O
+linkages	O
+.	O
+
+Thus	O
+treatment	O
+of	O
+
+the	O
+nonamer	O
+,	O
+d	O
+-	O
+ApApApApGpCpApApG	O
+,	O
+with	O
+spleen	O
+phosphodiesterase	O
+gave	O
+d	O
+-	O
+Ap	O
+and	O
+
+the	O
+octamer	O
+d	O
+-	O
+ApApApGpCpApApG	O
+whose	O
+retention	O
+time	O
+is	O
+16	O
+.	O
+4	O
+min	O
+on	O
+the	O
+reversed	O
+phase	O
+column	O
+.	O
+
+The	O
+noncharged	O
+octamer	O
+was	O
+freed	O
+of	O
+d	O
+-	O
+Ap	O
+and	O
+enzyne	O
+by	O
+simply	O
+passing	O
+it	O
+through	O
+a	O
+small	O
+DEAE	O
+cellulose	O
+column	O
+.	O
+
+Characterization	O
+.	O
+
+Methylphosphonate	O
+linkages	O
+are	O
+cleaved	O
+by	O
+base	O
+.	O
+
+We	O
+have	O
+found	O
+piperdine	O
+is	O
+particularly	O
+effective	O
+.	O
+
+The	O
+cleavage	O
+occurs	O
+in	O
+a	O
+random	O
+manner	O
+giving	O
+nucleosides	O
+,	O
+nucleoside	O
+3	O
+'	O
+-	O
+or	O
+5	O
+'	O
+-	O
+methylphosphonates	O
+and	O
+
+nucleoside	O
+3	O
+'	O
+,	O
+5	O
+'	O
+-	O
+bis	O
+-	O
+methylphosphonates	O
+.	O
+
+This	O
+hydrolysis	O
+reaction	O
+may	O
+be	O
+used	O
+to	O
+characterize	O
+dimers	O
+,	O
+since	O
+the	O
+identity	O
+and	O
+ratio	O
+of	O
+the	O
+products	O
+formed	O
+are	O
+easily	O
+determined	O
+by	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+However	O
+,	O
+the	O
+method	O
+becomes	O
+less	O
+satisfactory	O
+for	O
+longer	O
+oligomers	O
+.	O
+
+Purine	O
+-	O
+containing	O
+oligonucleoside	O
+methylphosphonates	O
+may	O
+be	O
+depurinated	O
+by	O
+treatment	O
+with	O
+hydrochloric	O
+acid	O
+at	O
+650	O
+.	O
+
+The	O
+methylphosphonate	O
+linkage	O
+is	O
+
+6238	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+9	O
+0	O
+OH	O
+cH3P	O
+:	O
+O	O
+cH	O
+CH3P	O
+
+9	O
+9	O
+
+CH	O
+-	O
+P	O
+:	O
+O	O
+C	O
+cH	O
+:	O
+0pO	O
+
+O	O
+~	O
+~	O
+~	O
+j4	O
+HO	O
+OP	O
+3	O
+0	O
+H	O
+0	O
+0OH0	O
+
+9	O
+S	O
+S	O
+
+Figure	O
+3	O
+:	O
+Hydrolysis	O
+of	O
+the	O
+internucleoside	O
+methylphsophonate	O
+linkages	O
+at	O
+an	O
+
+apurinic	O
+site	O
+produced	O
+by	O
+treatment	O
+of	O
+the	O
+oligomer	O
+with	O
+hydrochloric	O
+acid	O
+at	O
+pH	O
+2	O
+.	O
+
+resistant	O
+to	O
+hydrolysis	O
+by	O
+these	O
+conditions	O
+as	O
+shown	O
+by	O
+the	O
+stability	O
+of	O
+d	O
+-	O
+TpT	O
+and	O
+d	O
+-	O
+TpTpT	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+dimers	O
+or	O
+trimers	O
+containing	O
+purine	O
+bases	O
+
+such	O
+as	O
+d	O
+-	O
+ApA	O
+,	O
+dApT	O
+,	O
+dTpA	O
+or	O
+d	O
+-	O
+ApApA	O
+have	O
+half	O
+-	O
+lives	O
+between	O
+92	O
+and	O
+144	O
+min	O
+in	O
+0	O
+.	O
+01	O
+M	O
+hydrochloric	O
+acid	O
+.	O
+
+Following	O
+neutralization	O
+with	O
+ammonium	O
+hydroxide	O
+,	O
+the	O
+products	O
+of	O
+these	O
+reactions	O
+were	O
+characterized	O
+by	O
+reversed	O
+phase	O
+HPLC	O
+.	O
+
+d	O
+-	O
+ApA	O
+gave	O
+adenine	O
+,	O
+while	O
+both	O
+d	O
+-	O
+ApT	O
+and	O
+d	O
+-	O
+TpA	O
+gave	O
+adenine	O
+and	O
+thymidine	O
+as	O
+the	O
+sole	O
+products	O
+of	O
+the	O
+reaction	O
+.	O
+
+Adenine	O
+and	O
+d	O
+-	O
+ApA	O
+were	O
+the	O
+only	O
+products	O
+
+observed	O
+when	O
+d	O
+-	O
+ApApA	O
+was	O
+partially	O
+hydrolyzed	O
+.	O
+
+When	O
+d	O
+-	O
+CpCpApT	O
+was	O
+completely	O
+hydrolyzed	O
+in	O
+acid	O
+three	O
+products	O
+,	O
+d	O
+-	O
+CpC	O
+,	O
+adenine	O
+and	O
+thynidine	O
+,	O
+were	O
+observed	O
+in	O
+a	O
+molar	O
+ratio	O
+of	O
+1	O
+:	O
+1	O
+:	O
+1	O
+.	O
+
+In	O
+contrast	O
+to	O
+the	O
+base	O
+hydrolysis	O
+of	O
+the	O
+methylphosphonate	O
+group	O
+,	O
+apurinic	O
+sites	O
+produced	O
+by	O
+acid	O
+treatment	O
+are	O
+further	O
+hydrolyzed	O
+to	O
+
+nucleosides	O
+or	O
+oligomers	O
+with	O
+free	O
+5	O
+'	O
+-	O
+and	O
+3	O
+'	O
+-	O
+OH	O
+groups	O
+.	O
+
+The	O
+absence	O
+of	O
+
+terminal	O
+phosphonate	O
+residues	O
+suggests	O
+hydrolysis	O
+occurs	O
+as	O
+shown	O
+in	O
+Figure	O
+3	O
+.	O
+
+The	O
+OH	O
+group	O
+on	O
+the	O
+4	O
+'	O
+-	O
+carbon	O
+generated	O
+by	O
+opening	O
+the	O
+ribose	O
+at	O
+the	O
+apurinic	O
+site	O
+may	O
+participate	O
+in	O
+an	O
+intramolecular	O
+attack	O
+on	O
+the	O
+adjacent	O
+phosphonate	O
+linkages	O
+which	O
+results	O
+in	O
+removal	O
+of	O
+the	O
+phosphonate	O
+residues	O
+from	O
+the	O
+neighboring	O
+nucleoside	O
+hydroxyls	O
+.	O
+
+Previous	O
+studies	O
+by	O
+Agarwal	O
+and	O
+Riftina	O
+indicated	O
+dithymidine	O
+methyl	O
+-	O
+or	O
+phenylphosphonates	O
+can	O
+be	O
+phosphorylated	O
+by	O
+polynucleotide	O
+kinase	O
+(	O
+9	O
+)	O
+.	O
+
+Sinha	O
+et	O
+al	O
+.	O
+reported	O
+that	O
+dimers	O
+but	O
+not	O
+trimers	O
+or	O
+tetramers	O
+served	O
+as	O
+
+substrates	O
+for	O
+this	O
+enzyme	O
+(	O
+4	O
+)	O
+.	O
+
+We	O
+were	O
+unable	O
+to	O
+phosphorylate	O
+tetramers	O
+or	O
+longer	O
+oligomers	O
+which	O
+contain	O
+only	O
+methylphosphonate	O
+linkages	O
+.	O
+
+However	O
+,	O
+those	O
+oligomers	O
+which	O
+terminate	O
+with	O
+a	O
+5	O
+'	O
+-	O
+dAp	O
+-	O
+residue	O
+are	O
+readily	O
+
+6239	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+a	O
+
+ATP	O
+1	O
+
+1	O
+2	O
+3	O
+4	O
+
+b	O
+
+6	O
+mer	O
+Mik	O
+
+6	O
+mer	O
+go	O
+
+3mer	O
+a	O
+a	O
+a	O
+X	O
+2mer	O
+do	O
+ATP	O
+411	O
+
+12	O
+w	O
+34	O
+
+1	O
+2	O
+3	O
+4	O
+5	O
+6	O
+
+Figure	O
+4	O
+:	O
+(	O
+a	O
+)	O
+PEI	O
+-	O
+cellulose	O
+TLC	O
+of	O
+T4	O
+polynucleotide	O
+kinase	O
+reactions	O
+.	O
+
+1	O
+)	O
+[	O
+y	O
+-	O
+32p	O
+]	O
+ATP	O
+;	O
+2	O
+)	O
+d	O
+-	O
+ApApA	O
+reaction	O
+mixture	O
+;	O
+3	O
+)	O
+d	O
+-	O
+ApGpCpApApG	O
+
+reaction	O
+mixture	O
+;	O
+4	O
+)	O
+d	O
+-	O
+ApApApApG	O
+_	O
+pCpApAeG	O
+reaction	O
+mixture	O
+.	O
+
+The	O
+chromatogram	O
+was	O
+eluted	O
+wi	O
+th1	O
+.	O
+5	O
+M	O
+pyridinium	O
+formate	O
+,	O
+pH	O
+3	O
+.	O
+5	O
+.	O
+
+(	O
+b	O
+)	O
+Polyacrylamide	O
+gel	O
+electrophoresis	O
+of	O
+phosphoryljted	O
+
+olihonucleoside	O
+methylghosphonates	O
+.	O
+
+1	O
+)	O
+markers	O
+:	O
+d	O
+-	O
+pTpT	O
+(	O
+2	O
+mer	O
+)	O
+;	O
+d	O
+-	O
+,	O
+3pApApA	O
+(	O
+3	O
+mer	O
+)	O
+;	O
+d	O
+-	O
+2pApGpCpApApG	O
+(	O
+6	O
+mer	O
+)	O
+;	O
+
+d	O
+-	O
+32pApApApApGpCpApApG	O
+(	O
+9	O
+mer	O
+.	O
+
+Lanes	O
+2	O
+-	O
+4	O
+:	O
+products	O
+obtained	O
+
+after	O
+partTaT	O
+fy	O
+?	O
+rlysis	O
+of	O
+dl2pApApA	O
+(	O
+2	O
+)	O
+;	O
+d	O
+-	O
+2pApGpCpApApG	O
+(	O
+3	O
+)	O
+and	O
+d	O
+-	O
+32pApARApApGpCpAZARG	O
+;	O
+(	O
+4	O
+)	O
+with	O
+0	O
+.	O
+5	O
+M	O
+piperidine	O
+at	O
+377C	O
+for	O
+10	O
+min	O
+Lanel	O
+t	O
+:	O
+products	O
+obtained	O
+Wfter	O
+partial	O
+hydrolysis	O
+of	O
+d	O
+-	O
+3Kp	O
+-	O
+ApGRCpApApG	O
+(	O
+5	O
+)	O
+and	O
+d	O
+-	O
+32p	O
+-	O
+ApApAppGpjCppAjG	O
+(	O
+6	O
+)	O
+with	O
+0	O
+.	O
+5	O
+M	O
+HC1	O
+at	O
+371C	O
+fCor30	O
+min	O
+.	O
+
+Electrophoresis	O
+was	O
+carried	O
+out	O
+at	O
+
+constant	O
+voltage	O
+(	O
+800	O
+v	O
+)	O
+until	O
+the	O
+bromphenol	O
+blue	O
+marker	O
+dye	O
+had	O
+migrated	O
+halfway	O
+down	O
+the	O
+gel	O
+.	O
+
+phosphorylated	O
+by	O
+polynucleotide	O
+kinase	O
+.	O
+
+The	O
+phosphorylation	O
+reaction	O
+is	O
+easily	O
+followed	O
+by	O
+PEI	O
+-	O
+cellulose	O
+TLC	O
+.	O
+
+As	O
+shown	O
+in	O
+Figure	O
+4a	O
+,	O
+the	O
+phosphorylated	O
+oligomers	O
+have	O
+a	O
+higher	O
+Rf	O
+values	O
+than	O
+does	O
+d	O
+-	O
+ATP	O
+.	O
+
+The	O
+phosphorylated	O
+methylphosphonate	O
+oligomers	O
+can	O
+be	O
+separated	O
+according	O
+to	O
+their	O
+chain	O
+lengths	O
+by	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+on	O
+an	O
+18	O
+%	O
+gel	O
+
+containing	O
+7	O
+M	O
+urea	O
+as	O
+shown	O
+in	O
+Figure	O
+4	O
+(	O
+b	O
+)	O
+.	O
+
+Lane	O
+1	O
+shows	O
+the	O
+separation	O
+of	O
+a	O
+trimer	O
+,	O
+hexamer	O
+and	O
+nonamer	O
+.	O
+
+The	O
+band	O
+which	O
+appears	O
+directly	O
+below	O
+the	O
+
+nonamer	O
+may	O
+arise	O
+from	O
+traces	O
+of	O
+contaminating	O
+octamer	O
+which	O
+were	O
+not	O
+removed	O
+during	O
+the	O
+purification	O
+of	O
+d	O
+-	O
+ApApApApGpCpApApG	O
+.	O
+
+6240	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+When	O
+the	O
+oligomers	O
+were	O
+partially	O
+hydrolyzed	O
+with	O
+piperidine	O
+,	O
+a	O
+series	O
+of	O
+new	O
+bands	O
+appears	O
+corresponding	O
+to	O
+shorter	O
+oligomers	O
+produced	O
+via	O
+hydrolysis	O
+of	O
+the	O
+methylphosphonate	O
+linkages	O
+(	O
+Lanes	O
+2	O
+-	O
+4	O
+)	O
+.	O
+
+Because	O
+of	O
+the	O
+random	O
+nature	O
+of	O
+this	O
+cleavage	O
+reaction	O
+,	O
+the	O
+oligomers	O
+should	O
+terminate	O
+with	O
+either	O
+a	O
+3	O
+'	O
+-	O
+OH	O
+or	O
+a	O
+3	O
+'	O
+-	O
+methylphosphonate	O
+group	O
+.	O
+
+In	O
+the	O
+case	O
+of	O
+the	O
+trimer	O
+,	O
+32pApApA	O
+,	O
+
+hydrolysis	O
+gives	O
+two	O
+bands	O
+which	O
+correspond	O
+to	O
+d	O
+-	O
+32pApA	O
+and	O
+d	O
+-	O
+32pApAp	O
+(	O
+Lane	O
+2	O
+)	O
+.	O
+
+The	O
+same	O
+products	O
+are	O
+observed	O
+for	O
+hydrolysis	O
+of	O
+the	O
+nonamer	O
+,	O
+
+d	O
+-	O
+32pApApApApGpCpApApG	O
+(	O
+Lane	O
+4	O
+)	O
+.	O
+
+A	O
+similar	O
+situation	O
+is	O
+observed	O
+for	O
+
+d32pApGpCpApApG	O
+although	O
+the	O
+dimers	O
+d	O
+-	O
+32pApG	O
+and	O
+d	O
+-	O
+32pApGp	O
+have	O
+somewhat	O
+
+different	O
+mobilities	O
+(	O
+Lane	O
+3	O
+)	O
+.	O
+
+These	O
+dimers	O
+cannot	O
+be	O
+separated	O
+when	O
+the	O
+gel	O
+is	O
+run	O
+in	O
+the	O
+absence	O
+of	O
+urea	O
+.	O
+
+It	O
+is	O
+possible	O
+to	O
+determine	O
+the	O
+chain	O
+lengths	O
+of	O
+the	O
+original	O
+oligomers	O
+
+by	O
+counting	O
+the	O
+number	O
+of	O
+oligomers	O
+produced	O
+by	O
+partial	O
+piperidine	O
+hydrolysis	O
+.	O
+
+For	O
+example	O
+,	O
+starting	O
+with	O
+the	O
+trimer	O
+band	O
+,	O
+one	O
+can	O
+observe	O
+3	O
+bands	O
+
+corresponding	O
+to	O
+tetramer	O
+,	O
+pentamer	O
+and	O
+hexamer	O
+for	O
+the	O
+hydrolysis	O
+products	O
+of	O
+d	O
+-	O
+32pApGpCpApApG	O
+(	O
+Lane	O
+3	O
+)	O
+and	O
+6	O
+bands	O
+corresponding	O
+to	O
+tetramer	O
+,	O
+pentamer	O
+,	O
+hexamer	O
+,	O
+heptamer	O
+,	O
+octamer	O
+and	O
+nonamer	O
+for	O
+the	O
+hydrolysis	O
+products	O
+of	O
+
+32pApApApApGpCpApApG	O
+(	O
+Lane	O
+4	O
+)	O
+.	O
+
+The	O
+positions	O
+of	O
+the	O
+oligomers	O
+of	O
+the	O
+same	O
+
+chain	O
+length	O
+appear	O
+to	O
+be	O
+very	O
+similar	O
+which	O
+suggests	O
+that	O
+the	O
+mobilities	O
+are	O
+not	O
+greatly	O
+affected	O
+by	O
+base	O
+composition	O
+on	O
+the	O
+urea	O
+-	O
+containing	O
+gel	O
+.	O
+
+This	O
+
+procedure	O
+thus	O
+provides	O
+a	O
+rapid	O
+and	O
+convenient	O
+method	O
+for	O
+characterizing	O
+the	O
+methyl	O
+phosphonate	O
+ol	O
+i	O
+gomers	O
+.	O
+
+Treatment	O
+of	O
+the	O
+phosphorylated	O
+oligomers	O
+with	O
+acid	O
+produces	O
+shorter	O
+
+oligomers	O
+which	O
+result	O
+from	O
+chain	O
+cleavage	O
+at	O
+apurinic	O
+sites	O
+.	O
+
+In	O
+this	O
+case	O
+the	O
+oligomers	O
+terminate	O
+with	O
+a	O
+3	O
+'	O
+-	O
+OH	O
+group	O
+.	O
+
+Treatment	O
+of	O
+32pApGpCpApALpG	O
+
+produces	O
+an	O
+intense	O
+band	O
+corresponding	O
+to	O
+the	O
+pentamer	O
+,	O
+d	O
+-	O
+32pApGjCpAjA	O
+(	O
+Lane	O
+5	O
+)	O
+while	O
+treatment	O
+of	O
+32pApApApApGpCpApApG	O
+produces	O
+an	O
+intense	O
+band	O
+corresponding	O
+to	O
+the	O
+octamer	O
+d	O
+-	O
+32pApApAPApGpCpApA	O
+and	O
+fainter	O
+bands	O
+
+corresponding	O
+to	O
+the	O
+heptamer	O
+,	O
+hexamer	O
+,	O
+tetramer	O
+and	O
+trimer	O
+.	O
+
+These	O
+results	O
+suggest	O
+that	O
+under	O
+the	O
+conditions	O
+of	O
+the	O
+experiment	O
+,	O
+hydrolysis	O
+occurs	O
+preferentially	O
+at	O
+the	O
+3	O
+'	O
+-	O
+terminal	O
+G	O
+residue	O
+of	O
+both	O
+oligomers	O
+.	O
+
+It	O
+should	O
+be	O
+possible	O
+to	O
+extend	O
+this	O
+methodology	O
+to	O
+other	O
+base	O
+specific	O
+
+depurination	O
+or	O
+depyrimidination	O
+reactions	O
+similar	O
+to	O
+those	O
+employed	O
+in	O
+the	O
+Maxam	O
+-	O
+Gilbert	O
+sequencing	O
+method	O
+(	O
+10	O
+)	O
+.	O
+
+Experiments	O
+directed	O
+toward	O
+this	O
+goal	O
+are	O
+currently	O
+in	O
+progress	O
+and	O
+will	O
+be	O
+reported	O
+in	O
+a	O
+future	O
+communication	O
+.	O
+
+ACKNOWLEDGEMENT	O
+:	O
+This	O
+work	O
+was	O
+supported	O
+in	O
+part	O
+by	O
+the	O
+following	O
+grants	O
+from	O
+the	O
+National	O
+Institutes	O
+of	O
+Health	O
+:	O
+GM	O
+16066	O
+(	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+T	O
+.	O
+)	O
+and	O
+GM	O
+31927	O
+
+6241	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+(	O
+P	O
+.	O
+S	O
+.	O
+M	O
+.	O
+)	O
+,	O
+and	O
+from	O
+a	O
+grant	O
+from	O
+Association	O
+for	O
+International	O
+Cancer	O
+Research	O
+.	O
+
+REFERENCES	O
+:	O
+
+1	O
+.	O
+
+MTTITr	O
+,	O
+P	O
+.	O
+S	O
+.	O
+,	O
+McParland	O
+,	O
+K	O
+.	O
+B	O
+.	O
+,	O
+Jayaraman	O
+,	O
+K	O
+.	O
+and	O
+Ts	O
+'	O
+o	O
+,	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+
+(	O
+1981	O
+)	O
+
+Biochemistry	O
+20	O
+,	O
+1874	O
+-	O
+1880	O
+.	O
+
+2	O
+.	O
+
+Jayaraman	O
+,	O
+K	O
+.	O
+,	O
+McParland	O
+,	O
+K	O
+.	O
+B	O
+.	O
+,	O
+Miller	O
+,	O
+P	O
+.	O
+S	O
+.	O
+and	O
+Ts	O
+'	O
+o	O
+,	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+
+(	O
+1981	O
+)	O
+
+Proc	O
+.	O
+
+Natl	O
+.	O
+
+Acad	O
+.	O
+
+Sci	O
+.	O
+
+78	O
+,	O
+1537	O
+-	O
+1541	O
+.	O
+
+3	O
+.	O
+
+Miller	O
+,	O
+P	O
+.	O
+S	O
+.	O
+,	O
+Agris	O
+,	O
+C	O
+.	O
+H	O
+.	O
+,	O
+Blandin	O
+,	O
+M	O
+.	O
+,	O
+Murakami	O
+,	O
+A	O
+.	O
+,	O
+Reddy	O
+,	O
+P	O
+.	O
+M	O
+.	O
+,	O
+
+Spitz	O
+,	O
+S	O
+.	O
+A	O
+.	O
+and	O
+Ts	O
+'	O
+o	O
+,	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+
+(	O
+1983	O
+)	O
+Nucleic	O
+Acids	O
+Res	O
+.	O
+,	O
+submitted	O
+for	O
+publ	O
+ication	O
+.	O
+
+4	O
+.	O
+
+Sinha	O
+,	O
+N	O
+.	O
+D	O
+.	O
+
+Grossbruchaus	O
+,	O
+V	O
+.	O
+and	O
+Koester	O
+,	O
+H	O
+.	O
+
+(	O
+1983	O
+)	O
+Tetrahedron	O
+Letters	O
+
+24	O
+,	O
+877	O
+-	O
+880	O
+.	O
+
+5	O
+.	O
+
+Miller	O
+,	O
+P	O
+.	O
+S	O
+.	O
+,	O
+Cheng	O
+,	O
+D	O
+.	O
+M	O
+.	O
+,	O
+Dreon	O
+,	O
+N	O
+.	O
+,	O
+Jayaraman	O
+,	O
+K	O
+.	O
+,	O
+Kan	O
+,	O
+L	O
+.	O
+-	O
+S	O
+.	O
+,	O
+
+Leutzinger	O
+,	O
+E	O
+.	O
+E	O
+.	O
+,	O
+Pulford	O
+,	O
+S	O
+.	O
+M	O
+.	O
+and	O
+Ts	O
+'	O
+o	O
+,	O
+P	O
+.	O
+O	O
+.	O
+P	O
+.	O
+
+(	O
+1980	O
+)	O
+Biochemistry	O
+19	O
+,	O
+4688	O
+-	O
+4698	O
+.	O
+
+6	O
+.	O
+
+Ito	O
+,	O
+H	O
+.	O
+,	O
+Ike	O
+,	O
+Y	O
+.	O
+,	O
+Ikuta	O
+,	O
+S	O
+.	O
+and	O
+Itakura	O
+,	O
+K	O
+.	O
+,	O
+(	O
+1982	O
+)	O
+Nucleic	O
+Acids	O
+Res	O
+
+10	O
+,	O
+1755	O
+-	O
+1769	O
+.	O
+
+7	O
+.	O
+
+Barnett	O
+,	O
+R	O
+.	O
+W	O
+.	O
+and	O
+Letsinger	O
+,	O
+R	O
+.	O
+L	O
+.	O
+
+(	O
+1981	O
+)	O
+Tetrahedron	O
+Letters	O
+22	O
+,	O
+
+991	O
+-	O
+994	O
+.	O
+
+6242	O
+
+Further	O
+studies	O
+on	O
+partially	O
+purified	O
+calf	B
+thymus	O
+DNA	O
+polymerase	O
+a	O
+.	O
+
+Abstract	O
+
+Attempts	O
+to	O
+prevent	O
+the	O
+urea	O
+conversion	O
+of	O
+a	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+DNA	O
+polymerase	O
+alpha	O
+to	O
+a	O
+150	O
+-	O
+170	O
+,	O
+000	O
+molecular	O
+weight	O
+form	O
+by	O
+the	O
+inclusion	O
+of	O
+protease	O
+inhibitors	O
+have	O
+not	O
+been	O
+successful	O
+.	O
+
+No	O
+other	O
+method	O
+has	O
+been	O
+found	O
+capable	O
+of	O
+dissociating	O
+a	O
+50	O
+-	O
+70	O
+,	O
+000	O
+fragment	O
+or	O
+subunit	O
+from	O
+the	O
+DNA	O
+polymerase	O
+subunit	O
+.	O
+
+Addition	O
+of	O
+this	O
+50	O
+-	O
+70	O
+,	O
+000	O
+subunit	O
+to	O
+the	O
+polymerase	O
+subunit	O
+does	O
+not	O
+aid	O
+the	O
+binding	O
+of	O
+the	O
+enzyme	O
+to	O
+DNA	O
+,	O
+but	O
+does	O
+have	O
+an	O
+effect	O
+on	O
+the	O
+utilisation	O
+of	O
+synthetic	O
+template	O
+-	O
+initiator	O
+complexes	O
+by	O
+the	O
+polymerase	O
+subunit	O
+.	O
+
+Volume	O
+6	O
+Number	O
+10	O
+1979	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Further	O
+studies	O
+on	O
+partially	O
+purified	O
+calf	B
+thymus	O
+DNA	O
+polymerase	O
+a	O
+Keith	O
+McKune	O
+and	O
+Andrew	O
+M	O
+.	O
+Holmes	O
+*	O
+
+Biochemistry	O
+Department	O
+,	O
+Strathclyde	O
+University	O
+,	O
+The	O
+Todd	O
+Centre	O
+,	O
+31	O
+Taylor	O
+Street	O
+,	O
+Glasgow	O
+,	O
+G4	O
+ONR	O
+,	O
+UK	O
+
+Received	O
+I	O
+June	O
+1979	O
+ABSTRACT	O
+
+Attempts	O
+to	O
+prevent	O
+the	O
+urea	O
+conversion	O
+of	O
+a	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+DNA	O
+polymerase	O
+a	O
+to	O
+a	O
+150	O
+-	O
+170	O
+,	O
+000	O
+molecular	O
+weight	O
+form	O
+by	O
+the	O
+
+inclusion	O
+of	O
+protease	O
+inhibitors	O
+have	O
+not	O
+been	O
+successful	O
+.	O
+
+No	O
+other	O
+method	O
+has	O
+been	O
+found	O
+capable	O
+of	O
+dissociating	O
+a	O
+50	O
+-	O
+70	O
+,	O
+000	O
+fragment	O
+or	O
+subunit	O
+from	O
+the	O
+DNA	O
+polymerase	O
+subunit	O
+.	O
+
+Addition	O
+of	O
+this	O
+50	O
+-	O
+70	O
+,	O
+000	O
+subunit	O
+to	O
+the	O
+polymerase	O
+subunit	O
+does	O
+not	O
+aid	O
+the	O
+binding	O
+of	O
+the	O
+enzyme	O
+to	O
+DNA	O
+,	O
+but	O
+does	O
+have	O
+an	O
+effect	O
+on	O
+the	O
+utilisation	O
+of	O
+synthetic	O
+template	O
+-	O
+initiator	O
+complexes	O
+by	O
+the	O
+polymerase	O
+subunit	O
+.	O
+
+INTRODUCTION	O
+
+In	O
+mammals	O
+DNA	O
+polymerase	O
+a	O
+is	O
+thought	O
+to	O
+be	O
+the	O
+replicative	O
+
+enzyme	O
+,	O
+but	O
+due	O
+to	O
+low	O
+levels	O
+of	O
+activity	O
+,	O
+even	O
+in	O
+tissues	O
+actively	O
+making	O
+DNA	O
+,	O
+and	O
+to	O
+enzyme	O
+heterogeneity	O
+it	O
+has	O
+been	O
+found	O
+difficult	O
+to	O
+purify	O
+
+However	O
+,	O
+small	O
+samples	O
+of	O
+DNA	O
+polymerase	O
+a	O
+have	O
+been	O
+highly	O
+purified	O
+
+2	O
+,	O
+3	O
+,	O
+4	O
+,	O
+5	O
+from	O
+several	O
+sources	O
+and	O
+partially	O
+characterised	O
+
+Heterogeneity	O
+has	O
+been	O
+observed	O
+in	O
+DNA	O
+polymerase	O
+a	O
+from	O
+a	O
+var	O
+
+6	O
+7	O
+
+iety	O
+of	O
+sources	O
+,	O
+including	O
+rat	B
+liver	O
+and	O
+spleen	O
+,	O
+Hela	O
+cells	O
+,	O
+baby	O
+hamster	O
+
+8	O
+9	O
+,	O
+10	O
+11	O
+
+kidney	O
+cells	O
+,	O
+mouse	B
+myeloma	O
+,	O
+Drosophila	B
+embryos	O
+and	O
+calf	B
+thymus	O
+
+1	O
+,	O
+6	O
+,	O
+12	O
+,	O
+13	O
+.	O
+
+We	O
+have	O
+previously	O
+observed	O
+several	O
+species	O
+of	O
+calf	B
+thymus	O
+
+DNA	O
+polymerase	O
+a	O
+differing	O
+in	O
+size	O
+and	O
+charge	O
+.	O
+
+In	O
+order	O
+of	O
+elution	O
+from	O
+DEAE	O
+cellulose	O
+they	O
+are	O
+enzyme	O
+A1	O
+(	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+)	O
+,	O
+A2	O
+(	O
+200	O
+-	O
+230	O
+,	O
+000	O
+)	O
+,	O
+B	O
+(	O
+100	O
+-	O
+110	O
+,	O
+000	O
+)	O
+and	O
+C	O
+(	O
+150	O
+-	O
+170	O
+,	O
+000	O
+)	O
+.	O
+
+A	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+
+(	O
+dT	O
+)	O
+10	O
+preferring	O
+enzyme	O
+,	O
+enzyrrme	O
+D	O
+(	O
+140	O
+-	O
+150	O
+,	O
+000	O
+molecular	O
+weight	O
+)	O
+elutes	O
+just	O
+after	O
+enzyme	O
+B	O
+.	O
+
+The	O
+A	O
+enzymes	O
+seem	O
+identical	O
+in	O
+all	O
+properties	O
+except	O
+their	O
+charge	O
+.	O
+
+5	O
+.	O
+0	O
+-	O
+5	O
+.	O
+
+5S	O
+enzymes	O
+,	O
+analagous	O
+to	O
+B	O
+,	O
+have	O
+been	O
+observed	O
+to	O
+
+C	O
+Information	O
+Retrieval	O
+Limited	O
+1	O
+Falconberg	O
+Court	O
+London	O
+Wl	O
+V	O
+5FG	O
+England	O
+
+3341	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+arise	O
+as	O
+the	O
+result	O
+of	O
+proteolytic	O
+action	O
+'	O
+,	O
+similarly	O
+the	O
+B	O
+enzyme	O
+above	O
+14	O
+
+,	O
+but	O
+the	O
+relationship	O
+of	O
+the	O
+other	O
+observed	O
+species	O
+is	O
+not	O
+clear	O
+,	O
+nor	O
+is	O
+
+the	O
+problem	O
+of	O
+which	O
+,	O
+if	O
+any	O
+,	O
+of	O
+these	O
+species	O
+is	O
+the	O
+replicative	O
+enzyme	O
+,	O
+
+although	O
+circumstantial	O
+evidence	O
+has	O
+implicated	O
+a	O
+DNA	O
+polymerase	O
+a	O
+to	O
+be	O
+
+15	O
+the	O
+replicative	O
+enzyme	O
+in	O
+adenovirus	B
+infected	O
+KB	O
+cells	O
+
+We	O
+have	O
+previously	O
+shown	O
+that	O
+several	O
+of	O
+these	O
+enzymes	O
+are	O
+inter	O
+
+16	O
+
+convertible	O
+.	O
+
+In	O
+particular	O
+,	O
+mild	O
+urea	O
+treatment	O
+can	O
+convert	O
+both	O
+A	O
+
+enzymes	O
+to	O
+C	O
+enzyme	O
+,	O
+with	O
+the	O
+loss	O
+of	O
+a	O
+subunit	O
+or	O
+fragment	O
+of	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+.	O
+
+The	O
+C	O
+enzyme	O
+retains	O
+DNA	O
+polymerase	O
+activity	O
+,	O
+but	O
+
+does	O
+show	O
+differences	O
+compared	O
+to	O
+A	O
+enzyme	O
+in	O
+heat	O
+sensitivity	O
+and	O
+sensitivity	O
+to	O
+N	O
+-	O
+ethylmaleimide	O
+.	O
+
+Highly	O
+purified	O
+samples	O
+of	O
+A	O
+and	O
+C	O
+enzymes	O
+when	O
+subjected	O
+to	O
+sodium	O
+dodecyl	O
+sulphate	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+have	O
+shown	O
+a	O
+corre	O
+
+lation	O
+of	O
+DNA	O
+polymerase	O
+activity	O
+with	O
+a	O
+polypeptide	O
+band	O
+155	O
+,	O
+000	O
+molecular	O
+weight	O
+.	O
+
+Contaminating	O
+material	O
+of	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+appeared	O
+
+to	O
+obscure	O
+the	O
+putative	O
+50	O
+-	O
+70	O
+,	O
+000	O
+subunit	O
+in	O
+gels	O
+of	O
+A	O
+enzyme	O
+.	O
+
+The	O
+conclusions	O
+drawn	O
+were	O
+that	O
+DNA	O
+polymerase	O
+a	O
+is	O
+a	O
+155	O
+,	O
+000	O
+molecular	O
+weight	O
+
+polypeptide	O
+(	O
+C	O
+enzyrrme	O
+)	O
+which	O
+can	O
+and	O
+does	O
+associated	O
+with	O
+material	O
+of	O
+50	O
+
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+to	O
+give	O
+A	O
+enzyme	O
+,	O
+and	O
+that	O
+enzyme	O
+B	O
+is	O
+a	O
+proteol	O
+
+14	O
+
+ytic	O
+degradation	O
+product	O
+.	O
+
+The	O
+relationship	O
+of	O
+enzyme	O
+D	O
+to	O
+the	O
+others	O
+is	O
+
+not	O
+clear	O
+.	O
+
+It	O
+is	O
+possible	O
+that	O
+during	O
+the	O
+enzyme	O
+isolation	O
+procedure	O
+proteolytic	O
+action	O
+may	O
+have	O
+taken	O
+place	O
+on	O
+a	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+enzyme	O
+releasing	O
+155	O
+,	O
+000	O
+and	O
+50	O
+-	O
+70	O
+,	O
+000	O
+fragments	O
+which	O
+remain	O
+in	O
+association	O
+
+until	O
+urea	O
+treatment	O
+separates	O
+them	O
+.	O
+
+It	O
+is	O
+also	O
+possible	O
+that	O
+urea	O
+treatment	O
+itself	O
+renders	O
+the	O
+enzyme	O
+susceptible	O
+to	O
+contaminating	O
+proteases	O
+.	O
+
+Further	O
+experiments	O
+to	O
+ascertain	O
+whether	O
+or	O
+not	O
+this	O
+is	O
+the	O
+case	O
+and	O
+,	O
+if	O
+so	O
+,	O
+to	O
+prevent	O
+it	O
+,	O
+have	O
+been	O
+carried	O
+out	O
+.	O
+
+A	O
+enzyme	O
+can	O
+be	O
+reconstituted	O
+from	O
+C	O
+enzyme	O
+formed	O
+by	O
+the	O
+action	O
+
+of	O
+urea	O
+on	O
+A	O
+enzyme	O
+by	O
+concentrating	O
+it	O
+with	O
+the	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+material	O
+.	O
+
+The	O
+A	O
+enzyrme	O
+obtained	O
+in	O
+this	O
+manner	O
+is	O
+highly	O
+purified	O
+,	O
+as	O
+is	O
+
+the	O
+C	O
+enzyme	O
+formed	O
+by	O
+the	O
+urea	O
+treatment	O
+,	O
+and	O
+has	O
+been	O
+used	O
+in	O
+attempts	O
+to	O
+show	O
+differences	O
+in	O
+synthetic	O
+template	O
+-	O
+initiator	O
+complex	O
+utilisation	O
+
+3342	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+b	O
+y	O
+the	O
+se	O
+two	O
+enzyme	O
+s	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+
+Calf	B
+thymus	O
+was	O
+obtained	O
+from	O
+10	O
+-	O
+16	O
+week	O
+old	O
+calves	B
+and	O
+frozen	O
+at	O
+
+-	O
+20	O
+?	O
+C	O
+until	O
+required	O
+.	O
+
+Chromatographic	O
+media	O
+and	O
+chemicals	O
+were	O
+obtained	O
+
+6	O
+
+from	O
+sources	O
+previously	O
+referred	O
+to	O
+.	O
+
+Radioactive	O
+deoxynucleoside	O
+tri	O
+
+phosphates	O
+were	O
+obtained	O
+from	O
+the	O
+Radiochemical	O
+Centre	O
+,	O
+Amersham	O
+,	O
+Bucks	O
+.	O
+
+Synthetic	O
+oligo	O
+and	O
+polynucleotides	O
+were	O
+obtained	O
+from	O
+P	O
+.	O
+
+L	O
+.	O
+
+Biochemicals	O
+
+Inc	O
+.	O
+,	O
+except	O
+for	O
+poly	O
+(	O
+dC	O
+)	O
+which	O
+was	O
+a	O
+gift	O
+from	O
+Dr	O
+.	O
+I	O
+.	O
+R	O
+.	O
+
+Johnston	O
+and	O
+pre	O
+
+17	O
+
+pared	O
+from	O
+oligo	O
+d	O
+(	O
+C	O
+)	O
+5	O
+as	O
+described	O
+.	O
+
+N	O
+-	O
+a	O
+-	O
+p	O
+Tosyl	O
+-	O
+L	O
+-	O
+lysine	O
+chloromethy	O
+
+lketone	O
+HCl	O
+and	O
+phenylmethylsulphony	O
+were	O
+obtained	O
+from	O
+Sigma	O
+and	O
+Trasylol	O
+from	O
+Bayer	O
+.	O
+
+Except	O
+where	O
+indicated	O
+all	O
+buffers	O
+contained	O
+20	O
+%	O
+w	O
+/	O
+v	O
+glycerol	O
+and	O
+
+1	O
+mM	O
+dithiothreitol	O
+.	O
+
+Standard	O
+linear	O
+phosphate	O
+gradients	O
+were	O
+run	O
+between	O
+0	O
+.	O
+03	O
+M	O
+and	O
+0	O
+.	O
+25	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+.	O
+
+Gradient	O
+salt	O
+concentr	O
+
+2	O
+
+ations	O
+were	O
+measured	O
+using	O
+a	O
+conductivity	O
+meter	O
+as	O
+described	O
+.	O
+
+Urea	O
+was	O
+
+prepared	O
+as	O
+a	O
+4	O
+.	O
+
+8	O
+M	O
+solution	O
+in	O
+20	O
+%	O
+w	O
+/	O
+v	O
+glycerol	O
+,	O
+stirred	O
+with	O
+Amberlite	O
+
+MB3	O
+and	O
+filtered	O
+.	O
+
+Dithiothreitol	O
+was	O
+added	O
+to	O
+a	O
+final	O
+concentration	O
+of	O
+1	O
+mM	O
+before	O
+use	O
+.	O
+
+6	O
+DNA	O
+polymerase	O
+was	O
+assayed	O
+using	O
+activated	O
+DNA	O
+as	O
+described	O
+
+except	O
+that	O
+the	O
+buffer	O
+was	O
+50	O
+mM	O
+tris	O
+HC1	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+.	O
+
+One	O
+unit	O
+of	O
+DNA	O
+polymerase	O
+activity	O
+incorporates	O
+ln	O
+mol	O
+[	O
+H	O
+]	O
+dTMP	O
+into	O
+an	O
+acid	O
+insoluble	O
+form	O
+in	O
+one	O
+hour	O
+at	O
+370C	O
+.	O
+
+Assays	O
+using	O
+synthetic	O
+template	O
+-	O
+initiator	O
+complexes	O
+were	O
+carried	O
+out	O
+at	O
+30	O
+?	O
+C	O
+in	O
+0	O
+.	O
+
+12	O
+ml	O
+.	O
+
+The	O
+template	O
+-	O
+initiator	O
+complexes	O
+
+6	O
+
+were	O
+prepared	O
+and	O
+assays	O
+processed	O
+as	O
+described	O
+.	O
+
+All	O
+assays	O
+contained	O
+
+1	O
+mM	O
+dithiothreitol	O
+,	O
+62	O
+.	O
+
+5	O
+p	O
+.	O
+g	O
+bovine	B
+serum	O
+albumin	O
+,	O
+1	O
+,	O
+ug	O
+template	O
+-	O
+initiator	O
+complex	O
+,	O
+enzyme	O
+protein	O
+and	O
+the	O
+relevant	O
+[	O
+H	O
+]	O
+deoxynucleoside	O
+triphosphate	O
+at	O
+0	O
+.	O
+1	O
+mM	O
+and	O
+12	O
+-	O
+15	O
+cpm	O
+/	O
+pmol	O
+.	O
+
+These	O
+assays	O
+were	O
+carried	O
+out	O
+at	O
+either	O
+pH	O
+6	O
+.	O
+4	O
+in	O
+20	O
+mM	O
+sodium	O
+-	O
+potassium	O
+phosphate	O
+,	O
+or	O
+at	O
+pH	O
+7	O
+.	O
+8	O
+in	O
+50	O
+mM	O
+tris	O
+HCl	O
+and	O
+contained	O
+either	O
+10	O
+mM	O
+MgCl2	O
+or	O
+1	O
+mM	O
+MnCl2	O
+as	O
+indicated	O
+.	O
+
+Preliminary	O
+purification	O
+of	O
+DNA	O
+polymerase	O
+a	O
+to	O
+Fraction	O
+IV	O
+was	O
+as	O
+
+6	O
+
+described	O
+,	O
+the	O
+purification	O
+steps	O
+being	O
+phosphocellulose	O
+chromatography	O
+,	O
+
+ammonium	O
+sulphate	O
+precipitation	O
+and	O
+gel	O
+filtration	O
+on	O
+Sepharose	O
+6B	O
+.	O
+
+3343	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Enzyme	O
+obtained	O
+from	O
+the	O
+DEAE	O
+cellulose	O
+step	O
+is	O
+referred	O
+to	O
+as	O
+Fraction	O
+
+V	O
+enzyme	O
+.	O
+
+Samples	O
+were	O
+prepared	O
+for	O
+sodium	O
+dodecyl	O
+sulphate	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+and	O
+scanned	O
+as	O
+previously	O
+described2	O
+
+RESULTS	O
+AND	O
+DISCUSSION	O
+
+(	O
+a	O
+)	O
+Interconversion	O
+Studies	O
+
+A	O
+enzyme	O
+was	O
+routinely	O
+converted	O
+to	O
+C	O
+enzyme	O
+by	O
+incubating	O
+200500	O
+units	O
+/	O
+ml	O
+of	O
+Fraction	O
+V	O
+A	O
+enzyme	O
+in	O
+2	O
+.	O
+4	O
+M	O
+urea	O
+in	O
+0	O
+.	O
+
+02	O
+M	O
+potassium	O
+
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+,	O
+for	O
+60	O
+minutes	O
+at	O
+0	O
+?	O
+C	O
+.	O
+
+The	O
+mixture	O
+was	O
+then	O
+loaded	O
+on	O
+to	O
+a	O
+DEAE	O
+cellulose	O
+,	O
+washed	O
+with	O
+0	O
+.	O
+
+03	O
+M	O
+potassium	O
+phosphate	O
+pH	O
+7	O
+.	O
+
+8	O
+,	O
+and	O
+enzyrme	O
+eluted	O
+either	O
+with	O
+the	O
+standard	O
+phosphate	O
+gradient	O
+or	O
+batchwise	O
+.	O
+
+Under	O
+these	O
+conditions	O
+usually	O
+about	O
+50	O
+-	O
+60	O
+%	O
+of	O
+recovered	O
+activity	O
+was	O
+
+enzyme	O
+C	O
+(	O
+Fig	O
+1	O
+a	O
+)	O
+.	O
+
+Overall	O
+recovery	O
+was	O
+70	O
+-	O
+80	O
+%	O
+.	O
+
+A	O
+enzyme	O
+was	O
+recon	O
+
+14	O
+
+stituted	O
+essentially	O
+as	O
+described	O
+.	O
+
+The	O
+flow	O
+through	O
+material	O
+from	O
+the	O
+
+DEAE	O
+cellulose	O
+column	O
+after	O
+the	O
+urea	O
+treatment	O
+was	O
+loaded	O
+on	O
+to	O
+a	O
+1	O
+x	O
+0	O
+.	O
+
+8	O
+cm	O
+phosphocellulose	O
+column	O
+,	O
+washed	O
+with	O
+0	O
+.	O
+03	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+,	O
+and	O
+the	O
+protein	O
+eluted	O
+with	O
+0	O
+.	O
+25	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+
+8	O
+.	O
+
+This	O
+material	O
+,	O
+the	O
+putative	O
+subunit	O
+,	O
+was	O
+vacuum	O
+dialysed	O
+with	O
+the	O
+C	O
+enzyme	O
+produced	O
+by	O
+the	O
+urea	O
+treatment	O
+,	O
+rechromatographed	O
+on	O
+DEAE	O
+cellulose	O
+and	O
+enzyme	O
+eluted	O
+batchwise	O
+(	O
+Fig	O
+1	O
+b	O
+)	O
+.	O
+
+Recovery	O
+from	O
+this	O
+procedure	O
+was	O
+
+usually	O
+50	O
+-	O
+70	O
+%	O
+A	O
+enzyme	O
+.	O
+
+Overall	O
+recovery	O
+was	O
+30	O
+-	O
+40	O
+%	O
+of	O
+the	O
+C	O
+enzyme	O
+dialysed	O
+.	O
+
+If	O
+the	O
+material	O
+eluted	O
+from	O
+the	O
+phosphocellulose	O
+by	O
+the	O
+0	O
+.	O
+
+25	O
+M	O
+potassium	O
+phosphate	O
+was	O
+heated	O
+to	O
+90	O
+?	O
+C	O
+for	O
+5	O
+minutes	O
+prior	O
+to	O
+vacuum	O
+
+dialysis	O
+with	O
+the	O
+C	O
+enzyme	O
+the	O
+recovery	O
+from	O
+the	O
+DEAE	O
+cellulose	O
+column	O
+
+was	O
+significantly	O
+higher	O
+(	O
+60	O
+-	O
+70	O
+%	O
+of	O
+the	O
+original	O
+C	O
+enzyme	O
+activity	O
+)	O
+,	O
+but	O
+all	O
+recoverable	O
+DNA	O
+polymerase	O
+activity	O
+was	O
+C	O
+enzyme	O
+.	O
+
+This	O
+,	O
+together	O
+with	O
+the	O
+fact	O
+that	O
+the	O
+60	O
+minute	O
+treatment	O
+with	O
+urea	O
+has	O
+,	O
+on	O
+occasions	O
+,	O
+given	O
+
+rise	O
+to	O
+a	O
+50	O
+%	O
+increase	O
+in	O
+DNA	O
+polymerase	O
+activity	O
+prior	O
+to	O
+loading	O
+on	O
+to	O
+the	O
+DEAE	O
+cellulose	O
+column	O
+,	O
+would	O
+indicate	O
+that	O
+A	O
+enzyme	O
+is	O
+less	O
+active	O
+on	O
+
+activated	O
+DNA	O
+than	O
+is	O
+C	O
+enzyme	O
+.	O
+
+If	O
+the	O
+DEAE	O
+cellulose	O
+flow	O
+through	O
+material	O
+came	O
+from	O
+urea	O
+treatment	O
+of	O
+A2	O
+enzyme	O
+then	O
+A2	O
+was	O
+produced	O
+on	O
+reconstitution	O
+;	O
+if	O
+from	O
+A1	O
+then	O
+A1	O
+was	O
+produced	O
+.	O
+
+Although	O
+the	O
+mild	O
+urea	O
+treatment	O
+of	O
+A	O
+has	O
+been	O
+used	O
+to	O
+prepare	O
+C	O
+of	O
+
+3344	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+b	O
+
+120	O
+180	O
+C	O
+
+I	O
+I	O
+^	O
+
+Figure	O
+la	O
+DEAE	O
+cellulose	O
+chromatography	O
+after	O
+2	O
+.	O
+4	O
+M	O
+urea	O
+treatment	O
+.	O
+
+4	O
+,	O
+5000	O
+units	O
+,	O
+4	O
+.	O
+4	O
+mg	O
+of	O
+Fraction	O
+II	O
+A2	O
+enzyme	O
+were	O
+incubated	O
+with	O
+urea	O
+at	O
+a	O
+final	O
+concentration	O
+of	O
+2	O
+.	O
+4	O
+M	O
+for	O
+60	O
+minutes	O
+at	O
+0	O
+?	O
+C	O
+,	O
+loaded	O
+on	O
+to	O
+a	O
+5	O
+x	O
+1	O
+.	O
+4	O
+cm	O
+DEAE	O
+cellulose	O
+column	O
+,	O
+the	O
+column	O
+was	O
+washed	O
+with	O
+0	O
+.	O
+
+03	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+and	O
+a	O
+200	O
+ml	O
+standard	O
+phosphate	O
+gradient	O
+applied	O
+.	O
+
+2	O
+.	O
+3	O
+ml	O
+fractions	O
+were	O
+collected	O
+and	O
+10	O
+Rl	O
+assayed	O
+for	O
+5	O
+minutes	O
+.	O
+
+(	O
+o	O
+-	O
+o	O
+)	O
+no	O
+
+phenylmethylsulphony	O
+(	O
+*	O
+-	O
+*	O
+)	O
+3	O
+mM	O
+phenylmethylsulphony	O
+(	O
+-	O
+)	O
+phosphate	O
+gradient	O
+.	O
+
+Figure	O
+lb	O
+The	O
+reconstitution	O
+of	O
+A2	O
+enzyme	O
+.	O
+
+3000	O
+units	O
+for	O
+C	O
+enzyme	O
+
+derived	O
+by	O
+urea	O
+treatment	O
+of	O
+A2	O
+were	O
+vacuum	O
+dialysed	O
+with	O
+the	O
+DEAE	O
+cellulose	O
+flow	O
+through	O
+material	O
+after	O
+phosphocellulose	O
+chromatography	O
+and	O
+
+chromatographed	O
+on	O
+a	O
+2	O
+x	O
+1	O
+.	O
+
+2	O
+cm	O
+DEAE	O
+cellulose	O
+column	O
+.	O
+
+After	O
+washing	O
+with	O
+0	O
+.	O
+03	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+7	O
+,	O
+the	O
+enzymes	O
+were	O
+eluted	O
+batchwise	O
+with	O
+the	O
+above	O
+concentrations	O
+of	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+.	O
+
+1	O
+ml	O
+fractions	O
+were	O
+collected	O
+and	O
+10	O
+.	O
+l	O
+assayed	O
+for	O
+10	O
+minutes	O
+.	O
+
+3345	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+high	O
+specific	O
+activity	O
+it	O
+is	O
+possible	O
+that	O
+conversion	O
+of	O
+the	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+enzymes	O
+to	O
+a	O
+155	O
+-	O
+170	O
+,	O
+000	O
+species	O
+maybe	O
+due	O
+to	O
+unfolding	O
+of	O
+the	O
+molecule	O
+to	O
+allow	O
+limited	O
+attack	O
+by	O
+contaminating	O
+proteases	O
+.	O
+
+Accord	O
+
+ingly	O
+the	O
+urea	O
+conversion	O
+of	O
+A	O
+to	O
+C	O
+was	O
+investigated	O
+in	O
+the	O
+presence	O
+of	O
+certain	O
+protease	O
+inhibitors	O
+.	O
+
+The	O
+presence	O
+of	O
+the	O
+serine	O
+protease	O
+inhibitor	O
+
+phenylmethylsulphony	O
+-	O
+fluoride	O
+in	O
+the	O
+incubation	O
+and	O
+chromatography	O
+buffers	O
+did	O
+not	O
+affect	O
+the	O
+conversion	O
+of	O
+A2to	O
+C	O
+(	O
+Fig	O
+1	O
+a	O
+)	O
+.	O
+
+Likewise	O
+trasylol	O
+and	O
+Na	O
+-	O
+p	O
+Tosyl	O
+-	O
+L	O
+-	O
+lysine	O
+chloromethylketone	O
+HC1	O
+had	O
+no	O
+effect	O
+.	O
+
+However	O
+,	O
+protease	O
+action	O
+could	O
+have	O
+occurred	O
+earlier	O
+in	O
+the	O
+purification	O
+procedure	O
+and	O
+the	O
+urea	O
+could	O
+be	O
+separating	O
+two	O
+fragments	O
+.	O
+
+Usually	O
+the	O
+DEAE	O
+cellulose	O
+profile	O
+shows	O
+that	O
+the	O
+majority	O
+of	O
+the	O
+enzyme	O
+activity	O
+is	O
+present	O
+as	O
+A	O
+
+enzyme	O
+(	O
+Fig	O
+2	O
+)	O
+.	O
+
+In	O
+this	O
+instance	O
+A1	O
+and	O
+A2	O
+have	O
+not	O
+been	O
+separated	O
+.	O
+
+When	O
+the	O
+temperature	O
+of	O
+the	O
+material	O
+in	O
+the	O
+original	O
+blending	O
+procedure	O
+was	O
+kept	O
+below	O
+0	O
+?	O
+C	O
+or	O
+phenylmethylsulphony	O
+,	O
+N	O
+-	O
+a	O
+-	O
+p	O
+Tosyl	O
+-	O
+L	O
+-	O
+lysine	O
+chloromethylketone	O
+HCl	O
+or	O
+trasylol	O
+was	O
+included	O
+in	O
+the	O
+isolation	O
+buffers	O
+the	O
+DEAE	O
+cellulose	O
+profile	O
+was	O
+similar	O
+.	O
+
+The	O
+A	O
+enzymes	O
+were	O
+still	O
+capable	O
+of	O
+conversion	O
+by	O
+mild	O
+urea	O
+treatment	O
+to	O
+C	O
+enzyme	O
+,	O
+indicating	O
+that	O
+if	O
+protease	O
+activity	O
+is	O
+involved	O
+then	O
+it	O
+is	O
+not	O
+susceptible	O
+to	O
+these	O
+inhibitors	O
+.	O
+
+When	O
+the	O
+calf	B
+
+20FI	O
+:	O
+Now	O
+~	O
+~	O
+~	O
+20	O
+20Fr	O
+Na	O
+06	O
+
+Figure	O
+2	O
+DEAE	O
+cellulose	O
+elution	O
+profile	O
+of	O
+calf	B
+thymus	O
+DNA	O
+polymerase	O
+a	O
+.	O
+
+47	O
+,	O
+000	O
+units	O
+,	O
+97	O
+mg	O
+of	O
+Fraction	O
+IV	O
+enzyme	O
+prepared	O
+from	O
+415	O
+g	O
+of	O
+calf	B
+
+thymus	O
+were	O
+loaded	O
+on	O
+to	O
+a	O
+10	O
+x	O
+1	O
+.	O
+8	O
+cm	O
+DEAE	O
+cellulose	O
+column	O
+,	O
+after	O
+washing	O
+with	O
+0	O
+.	O
+
+03	O
+M	O
+potassium	O
+phosphate	O
+,	O
+pH	O
+7	O
+.	O
+
+8	O
+a	O
+400	O
+ml	O
+standard	O
+phosphate	O
+gradient	O
+was	O
+applied	O
+.	O
+
+5	O
+ml	O
+fractions	O
+were	O
+collected	O
+and	O
+10	O
+,	O
+ul	O
+assayed	O
+for	O
+5	O
+minutes	O
+.	O
+
+3346	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+thymus	O
+was	O
+allowed	O
+to	O
+warm	O
+up	O
+during	O
+the	O
+blending	O
+procedure	O
+,	O
+or	O
+the	O
+supernatant	O
+prior	O
+to	O
+phosphocellulose	O
+chromatography	O
+was	O
+heated	O
+to	O
+37	O
+?	O
+C	O
+for	O
+30	O
+minutes	O
+,	O
+there	O
+was	O
+a	O
+marked	O
+decrease	O
+in	O
+the	O
+amount	O
+of	O
+A	O
+enzyme	O
+with	O
+a	O
+concomitant	O
+increase	O
+in	O
+the	O
+amount	O
+of	O
+B	O
+and	O
+C	O
+(	O
+unpublished	O
+observation	O
+)	O
+.	O
+
+The	O
+presence	O
+of	O
+phenylmethylsulphony	O
+,	O
+N	O
+-	O
+a	O
+-	O
+p	O
+T	O
+osyl	O
+-	O
+L	O
+-	O
+lysine	O
+
+chloromethylketone	O
+HCl	O
+or	O
+trasylol	O
+under	O
+these	O
+conditions	O
+only	O
+had	O
+a	O
+marginal	O
+effect	O
+on	O
+the	O
+appearance	O
+of	O
+C	O
+enzyme	O
+,	O
+but	O
+did	O
+reduce	O
+the	O
+amount	O
+of	O
+B	O
+
+enzyme	O
+.	O
+
+Heating	O
+the	O
+enzyme	O
+to	O
+37	O
+?	O
+C	O
+after	O
+the	O
+phosphocellulose	O
+step	O
+had	O
+no	O
+effect	O
+on	O
+the	O
+DEAE	O
+cellulose	O
+elution	O
+profile	O
+.	O
+
+Attempts	O
+to	O
+convert	O
+A	O
+enzyme	O
+to	O
+C	O
+using	O
+trypsin	O
+have	O
+not	O
+been	O
+successful	O
+.	O
+
+A	O
+enzyme	O
+activity	O
+is	O
+lost	O
+without	O
+the	O
+appearance	O
+of	O
+any	O
+other	O
+species	O
+(	O
+unpublished	O
+observation	O
+)	O
+,	O
+although	O
+
+14	O
+the	O
+action	O
+of	O
+trypsin	O
+on	O
+C	O
+enzyme	O
+can	O
+give	O
+rise	O
+to	O
+small	O
+amounts	O
+of	O
+B	O
+
+Although	O
+the	O
+conversion	O
+of	O
+A	O
+enzyme	O
+to	O
+C	O
+does	O
+not	O
+appear	O
+to	O
+be	O
+the	O
+result	O
+of	O
+serine	O
+protease	O
+action	O
+,	O
+proteases	O
+other	O
+than	O
+serine	O
+proteases	O
+
+18	O
+
+could	O
+have	O
+been	O
+responsible	O
+.	O
+
+Also	O
+,	O
+the	O
+fact	O
+that	O
+A	O
+enzyme	O
+can	O
+be	O
+recon	O
+
+stituted	O
+from	O
+C	O
+plus	O
+the	O
+flow	O
+through	O
+material	O
+from	O
+the	O
+DEAE	O
+cellulose	O
+after	O
+urea	O
+treatment	O
+does	O
+not	O
+necessarily	O
+mean	O
+we	O
+are	O
+dealing	O
+with	O
+two	O
+subunits	O
+as	O
+fragments	O
+produced	O
+by	O
+proteases	O
+mray	O
+be	O
+reassembled	O
+to	O
+give	O
+active	O
+
+enzyme	O
+9	O
+.	O
+
+However	O
+,	O
+the	O
+fact	O
+that	O
+a	O
+200	O
+-	O
+230	O
+,	O
+000	O
+molecular	O
+weight	O
+polypeptide	O
+band	O
+has	O
+never	O
+been	O
+observed	O
+in	O
+sodium	O
+dodecylsulphate	O
+polyacrylamride	O
+gels	O
+of	O
+highly	O
+purified	O
+A	O
+enzyme	O
+,	O
+or	O
+even	O
+cruder	O
+fractions	O
+of	O
+A	O
+
+enzyrre	O
+(	O
+unpublished	O
+observation	O
+)	O
+,	O
+may	O
+be	O
+significant	O
+.	O
+
+One	O
+might	O
+expect	O
+
+some	O
+of	O
+the	O
+enzyme	O
+not	O
+to	O
+have	O
+been	O
+attacked	O
+by	O
+whatever	O
+is	O
+responsible	O
+for	O
+cleaving	O
+the	O
+molecule	O
+,	O
+if	O
+,	O
+indeed	O
+,	O
+this	O
+does	O
+happen	O
+.	O
+
+It	O
+would	O
+appear	O
+,	O
+therefore	O
+,	O
+that	O
+the	O
+A	O
+enzyme	O
+consists	O
+of	O
+subunits	O
+of	O
+155	O
+,	O
+000	O
+and	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+with	O
+the	O
+small	O
+subunit	O
+having	O
+a	O
+slightly	O
+different	O
+charge	O
+in	O
+the	O
+
+case	O
+of	O
+A	O
+and	O
+A2	O
+.	O
+
+It	O
+has	O
+also	O
+been	O
+concluded	O
+that	O
+the	O
+heterogeneity	O
+in	O
+the	O
+
+1	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+~	O
+3	O
+mouse	B
+myeloma	O
+DNA	O
+polymerase	O
+a	O
+fraction	O
+is	O
+not	O
+due	O
+to	O
+proteolysis	O
+.	O
+
+However	O
+,	O
+the	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+subunit	O
+has	O
+not	O
+yet	O
+been	O
+identified	O
+.	O
+
+Sodiurrm	O
+dodecylsulphate	O
+polyacrylamide	O
+gels	O
+of	O
+reconstituted	O
+A	O
+enzyme	O
+have	O
+shown	O
+polypeptide	O
+bands	O
+at	O
+150	O
+-	O
+160	O
+,	O
+000	O
+and	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+
+(	O
+Fig	O
+.	O
+3	O
+)	O
+,	O
+but	O
+the	O
+ratio	O
+of	O
+staining	O
+intensity	O
+of	O
+the	O
+bands	O
+does	O
+not	O
+correspond	O
+to	O
+a	O
+1	O
+:	O
+1	O
+relationship	O
+.	O
+
+The	O
+ratio	O
+of	O
+the	O
+two	O
+bands	O
+is	O
+variable	O
+but	O
+is	O
+usually	O
+between	O
+1	O
+:	O
+2	O
+and	O
+1	O
+:	O
+3	O
+,	O
+indicating	O
+,	O
+perhaps	O
+,	O
+that	O
+more	O
+than	O
+one	O
+subunit	O
+of	O
+50	O
+
+3347	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+TOP	O
+123	O
+4	O
+5	O
+6	O
+
+Figure	O
+3	O
+Scan	O
+of	O
+a	O
+5	O
+%	O
+sodium	O
+dodecyl	O
+sulphate	O
+polyacrylamide	O
+gel	O
+of	O
+
+reconstituted	O
+A2	O
+enzyme	O
+.	O
+
+1500	O
+units	O
+of	O
+reconstituted	O
+A2	O
+enzyme	O
+were	O
+subjected	O
+to	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+under	O
+non	O
+-	O
+denaturing	O
+conditions	O
+.	O
+
+The	O
+gels	O
+were	O
+sliced	O
+,	O
+enzyme	O
+extracted	O
+and	O
+assayed	O
+and	O
+the	O
+peak	O
+
+fraction	O
+of	O
+DNA	O
+polymerase	O
+activity	O
+from	O
+three	O
+gels	O
+were	O
+pooled	O
+,	O
+subjected	O
+to	O
+sodium	O
+dodecyl	O
+sulphate	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+on	O
+a	O
+single	O
+
+gel	O
+,	O
+stained	O
+and	O
+scanned	O
+at	O
+2	O
+volt	O
+sensitivity	O
+as	O
+described2	O
+.	O
+
+The	O
+molecular	O
+weight	O
+standards	O
+were	O
+:	O
+(	O
+1	O
+)	O
+bovine	B
+serum	O
+albumin	O
+dimer	O
+(	O
+134	O
+,	O
+000	O
+)	O
+,	O
+(	O
+2	O
+)	O
+,	O
+3	O
+galactosidase	O
+(	O
+130	O
+,	O
+000	O
+)	O
+,	O
+(	O
+3	O
+)	O
+phosphorylase	O
+a	O
+(	O
+94	O
+,	O
+000	O
+)	O
+,	O
+(	O
+4	O
+)	O
+bovine	B
+serum	O
+
+albumin	O
+(	O
+68	O
+,	O
+000	O
+)	O
+,	O
+(	O
+5	O
+)	O
+pyruvate	O
+kinase	O
+(	O
+57	O
+,	O
+000	O
+)	O
+and	O
+(	O
+6	O
+)	O
+lactate	O
+dehydrogenase	O
+(	O
+35	O
+,	O
+000	O
+)	O
+.	O
+
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+can	O
+associate	O
+with	O
+the	O
+155	O
+,	O
+000	O
+subunit	O
+.	O
+
+The	O
+proportion	O
+of	O
+the	O
+lower	O
+molecular	O
+weight	O
+polypeptide	O
+band	O
+is	O
+higher	O
+in	O
+the	O
+reconstituted	O
+A	O
+enzyrrme	O
+than	O
+in	O
+the	O
+C	O
+enzyme	O
+preparation	O
+from	O
+which	O
+it	O
+was	O
+formed	O
+,	O
+but	O
+even	O
+the	O
+C	O
+enzyme	O
+contained	O
+some	O
+material	O
+in	O
+the	O
+region	O
+.	O
+
+Breakdown	O
+of	O
+material	O
+from	O
+155	O
+,	O
+000	O
+to	O
+50	O
+-	O
+70	O
+,	O
+000	O
+may	O
+be	O
+partly	O
+responsible	O
+for	O
+the	O
+contamination	O
+,	O
+but	O
+the	O
+presence	O
+of	O
+phenylmethylsulphony	O
+in	O
+samples	O
+in	O
+preparation	O
+for	O
+sodium	O
+dodecylsulphate	O
+polyacrylamide	O
+gel	O
+electrophoresis	O
+has	O
+not	O
+been	O
+successful	O
+in	O
+preventing	O
+it	O
+.	O
+
+The	O
+human	B
+KB	O
+cell	O
+
+DNA	O
+polymerase	O
+a	O
+,	O
+equivalent	O
+to	O
+the	O
+C	O
+enzyme	O
+,	O
+has	O
+been	O
+reported	O
+to	O
+consist	O
+
+4	O
+
+of	O
+subunits	O
+of	O
+76	O
+,	O
+000	O
+and	O
+66	O
+,	O
+000	O
+molecular	O
+weight	O
+,	O
+but	O
+at	O
+no	O
+time	O
+have	O
+we	O
+
+observed	O
+polypeptide	O
+bands	O
+at	O
+76	O
+,	O
+000	O
+and	O
+66	O
+,	O
+000	O
+rising	O
+and	O
+falling	O
+with	O
+
+enzyme	O
+activity	O
+in	O
+any	O
+gels	O
+of	O
+calf	B
+thyrrmus	O
+enzymes	O
+A1	O
+,	O
+A	O
+and	O
+C	O
+(	O
+and	O
+
+2	O
+unpublished	O
+observations	O
+)	O
+.	O
+
+(	O
+b	O
+)	O
+Template	O
+Studies	O
+
+Use	O
+has	O
+been	O
+made	O
+of	O
+the	O
+urea	O
+conversion	O
+of	O
+A	O
+to	O
+C	O
+and	O
+of	O
+the	O
+reconstitution	O
+of	O
+A	O
+enzyme	O
+to	O
+obtain	O
+samples	O
+of	O
+highly	O
+purified	O
+DNA	O
+polymerase	O
+,	O
+
+specific	O
+activity	O
+in	O
+excess	O
+of	O
+50	O
+,	O
+000	O
+units	O
+/	O
+mg	O
+,	O
+in	O
+order	O
+to	O
+study	O
+the	O
+effect	O
+of	O
+this	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+subunit	O
+on	O
+the	O
+DNA	O
+polymerase	O
+subunit	O
+.	O
+
+Previous	O
+results	O
+have	O
+indicated	O
+that	O
+A	O
+enzyrrme	O
+is	O
+stabler	O
+to	O
+heat	O
+and	O
+less	O
+
+3348	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+14	O
+,	O
+21	O
+
+susceptible	O
+to	O
+N	O
+-	O
+ethylmaleimide	O
+than	O
+C	O
+enzyme	O
+.	O
+
+It	O
+has	O
+been	O
+reported	O
+
+that	O
+highly	O
+purified	O
+DNA	O
+polymerase	O
+a	O
+can	O
+be	O
+associated	O
+with	O
+a	O
+protein	O
+capable	O
+of	O
+binding	O
+to	O
+DNA	O
+containing	O
+no	O
+3	O
+'	O
+OH	O
+ends	O
+and	O
+capable	O
+of	O
+being	O
+released	O
+during	O
+the	O
+DNA	O
+polymerase	O
+assay	O
+.	O
+
+Attempts	O
+to	O
+dissociate	O
+the	O
+50	O
+
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+subunit	O
+from	O
+the	O
+polymerase	O
+subunit	O
+by	O
+incubating	O
+A2	O
+with	O
+DNA	O
+polymerase	O
+reaction	O
+mixes	O
+containing	O
+activated	O
+DNA	O
+,	O
+poly	O
+
+(	O
+dA	O
+-	O
+T	O
+)	O
+and	O
+poly	O
+(	O
+dT	O
+)	O
+.	O
+oligo	O
+(	O
+A	O
+)	O
+10	O
+followed	O
+by	O
+ultracentrifugation	O
+in	O
+high	O
+salt	O
+have	O
+been	O
+unsuccessful	O
+.	O
+
+Similarly	O
+A	O
+absorbed	O
+and	O
+eluted	O
+from	O
+either	O
+native	O
+or	O
+denatured	O
+DNA	O
+cellulose	O
+remained	O
+A	O
+enzyme	O
+.	O
+
+Both	O
+A	O
+and	O
+C	O
+enzymes	O
+
+were	O
+eluted	O
+from	O
+the	O
+DNA	O
+celluloses	O
+by	O
+less	O
+than	O
+0	O
+.	O
+
+1	O
+M	O
+NaCl	O
+so	O
+it	O
+does	O
+not	O
+appear	O
+that	O
+the	O
+subunit	O
+enhances	O
+the	O
+binding	O
+of	O
+the	O
+DNA	O
+polymerase	O
+subunit	O
+to	O
+DNA	O
+.	O
+
+However	O
+,	O
+there	O
+are	O
+differences	O
+in	O
+the	O
+response	O
+of	O
+A	O
+and	O
+C	O
+
+enzymes	O
+to	O
+synthetic	O
+template	O
+-	O
+initiator	O
+complexes	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+Even	O
+if	O
+one	O
+takes	O
+into	O
+account	O
+the	O
+fact	O
+that	O
+A	O
+enzyme	O
+is	O
+less	O
+active	O
+on	O
+activated	O
+DNA	O
+
+than	O
+C	O
+enzyme	O
+(	O
+the	O
+addition	O
+of	O
+the	O
+50	O
+-	O
+70	O
+,	O
+000	O
+subunit	O
+to	O
+the	O
+polymerase	O
+subunit	O
+appears	O
+to	O
+result	O
+in	O
+a	O
+decrease	O
+of	O
+about	O
+30	O
+%	O
+of	O
+polymerase	O
+activity	O
+on	O
+activated	O
+DNA	O
+)	O
+the	O
+A	O
+enzyme	O
+is	O
+still	O
+more	O
+active	O
+on	O
+these	O
+templates	O
+.	O
+
+Although	O
+there	O
+is	O
+a	O
+variation	O
+in	O
+activity	O
+on	O
+these	O
+template	O
+-	O
+initiator	O
+comp	O
+
+lexes	O
+each	O
+time	O
+assays	O
+are	O
+carried	O
+out	O
+on	O
+them	O
+depending	O
+on	O
+the	O
+method	O
+of	O
+preparing	O
+the	O
+complexes	O
+and	O
+the	O
+base	O
+ratio	O
+of	O
+template	O
+to	O
+initiator	O
+,	O
+A	O
+enzyme	O
+always	O
+seems	O
+to	O
+be	O
+significantly	O
+more	O
+active	O
+than	O
+C	O
+.	O
+
+The	O
+A2	O
+
+enzyme	O
+at	O
+pH	O
+7	O
+.	O
+8	O
+,	O
+with	O
+extra	O
+subunit	O
+(	O
+s	O
+)	O
+is	O
+clearly	O
+more	O
+effective	O
+on	O
+the	O
+
+oligoribonucleotide	O
+initiator	O
+,	O
+oligo	O
+(	O
+A	O
+)	O
+10	O
+than	O
+is	O
+enzyme	O
+C	O
+.	O
+
+In	O
+view	O
+of	O
+the	O
+proposed	O
+RNA	O
+initiation	O
+of	O
+Okazaki	O
+pieces	O
+this	O
+may	O
+indicate	O
+a	O
+role	O
+of	O
+this	O
+subunit	O
+in	O
+Okazaki	O
+piece	O
+synthesis	O
+,	O
+in	O
+that	O
+it	O
+may	O
+aid	O
+the	O
+DNA	O
+polymerase	O
+to	O
+'	O
+take	O
+over	O
+'	O
+from	O
+the	O
+RNA	O
+polymerase	O
+.	O
+
+Using	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+(	O
+dT	O
+)	O
+10	O
+
+(	O
+A	O
+:	O
+T	O
+=	O
+20	O
+:	O
+1	O
+)	O
+and	O
+following	O
+the	O
+incorporation	O
+of	O
+[	O
+H	O
+]	O
+dTMP	O
+as	O
+a	O
+function	O
+of	O
+time	O
+a	O
+short	O
+lag	O
+was	O
+observed	O
+for	O
+C	O
+enzyme	O
+,	O
+but	O
+not	O
+for	O
+A2	O
+(	O
+Fig	O
+.	O
+4	O
+)	O
+.	O
+
+Similar	O
+re	O
+sult	O
+s	O
+we	O
+re	O
+obtained	O
+when	O
+poly	O
+(	O
+dC	O
+)	O
+.	O
+oligo	O
+(	O
+dG	O
+)	O
+1	O
+0	O
+(	O
+C	O
+:	O
+G	O
+=	O
+5	O
+:	O
+1	O
+)	O
+wa	O
+s	O
+
+used	O
+as	O
+temrrplate	O
+-	O
+initiator	O
+,	O
+but	O
+not	O
+when	O
+poly	O
+(	O
+dT	O
+)	O
+.	O
+oligo	O
+(	O
+A	O
+)	O
+10	O
+(	O
+T	O
+:	O
+A	O
+=	O
+1	O
+:	O
+1	O
+)	O
+was	O
+used	O
+.	O
+
+Neither	O
+enzyme	O
+showed	O
+a	O
+lag	O
+on	O
+this	O
+template	O
+-	O
+initiator	O
+complex	O
+or	O
+on	O
+activated	O
+DNA	O
+.	O
+
+Incorporation	O
+versus	O
+enzyme	O
+concentration	O
+also	O
+showed	O
+this	O
+lag	O
+for	O
+C	O
+enzyme	O
+on	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+(	O
+dT	O
+)	O
+10	O
+.	O
+
+It	O
+is	O
+not	O
+certain	O
+what	O
+causes	O
+
+3349	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+TABLE	O
+1	O
+Template	O
+utilisation	O
+by	O
+reconstituted	O
+A	O
+and	O
+C	O
+derived	O
+from	O
+A	O
+.	O
+
+3H	O
+]	O
+dNTP	O
+Divalent	O
+cation	O
+A2	O
+at	O
+pH	O
+C	O
+at	O
+pH	O
+
+Template	O
+_	O
+6	O
+.	O
+4	O
+7	O
+.	O
+8	O
+6	O
+.	O
+4	O
+7	O
+.	O
+8	O
+Activated	O
+DNA	O
+dTTP	O
+Mg	O
++	O
++	O
+100	O
+100	O
+Activated	O
+DNA	O
+dATP	O
+Mg	O
++	O
++	O
+91	O
+85	O
+Activated	O
+DNA	O
+dGTP	O
+Mg	O
++	O
++	O
+85	O
+82	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+(	O
+dT	O
+)	O
+10	O
+dTTP	O
+Mg	O
+66	O
+.	O
+0	O
+4	O
+.	O
+0	O
+20	O
+91	O
+
+(	O
+A	O
+:	O
+T	O
+=	O
+20	O
+:	O
+1	O
+)	O
+
+poly	O
+(	O
+dA	O
+)	O
+.	O
+
+oligo	O
+(	O
+dT	O
+)	O
+dTTP	O
+Mu	O
+19	O
+.	O
+0	O
+4	O
+.	O
+
+5	O
+6	O
+.	O
+
+5	O
+2	O
+.	O
+5	O
+
+poly	O
+(	O
+dA	O
+.	O
+
+oig	O
+~	O
+10	O
+(	O
+A	O
+:	O
+T	O
+=	O
+20	O
+:	O
+1	O
+)	O
+
+poly	O
+(	O
+dT	O
+)	O
+.	O
+
+oligo	O
+(	O
+dA	O
+)	O
+10	O
+dATP	O
+Mg	O
+2	O
+.	O
+5	O
+<	O
+1	O
+(	O
+1	O
+(	O
+1	O
+
+(	O
+T	O
+:	O
+A	O
+=	O
+5	O
+:	O
+1	O
+)	O
+
+poly	O
+(	O
+dT	O
+)	O
+.	O
+oligo	O
+(	O
+dA	O
+)	O
+1	O
+dATP	O
+Mn	O
++	O
++	O
+15	O
+.	O
+5	O
+23	O
+.	O
+0	O
+9	O
+.	O
+
+0	O
+3	O
+.	O
+
+0	O
+
+poly	O
+(	O
+dT	O
+)	O
+.	O
+
+oligo	O
+(	O
+A	O
+)	O
+10	O
+dATP	O
+Mg	O
+15	O
+.	O
+0	O
+230	O
+.	O
+0	O
+10	O
+.	O
+0	O
+77	O
+.	O
+
+5	O
+
+(	O
+T	O
+:	O
+A	O
+=	O
+1	O
+:	O
+1	O
+)	O
+
+poly	O
+(	O
+dT	O
+)	O
+*	O
+oligo	O
+(	O
+A	O
+)	O
+10	O
+dATP	O
+Mn	O
+41	O
+.	O
+5	O
+75	O
+.	O
+
+5	O
+19	O
+.	O
+5	O
+21	O
+.	O
+5	O
+
+(	O
+T	O
+:	O
+A	O
+=	O
+1	O
+:	O
+1	O
+)	O
+
+poly	O
+(	O
+dC	O
+)	O
+.	O
+
+oligo	O
+(	O
+dG	O
+)	O
+dGTP	O
+Mg	O
++	O
++	O
+6	O
+.	O
+
+0	O
+15	O
+.	O
+5	O
+4	O
+.	O
+
+5	O
+7	O
+.	O
+
+5	O
+
+(	O
+C	O
+:	O
+G	O
+=	O
+5	O
+:	O
+1	O
+)	O
+10	O
+
+poly	O
+(	O
+dC	O
+)	O
+.	O
+
+oligo	O
+(	O
+dG	O
+)	O
+10	O
+dGTP	O
+Mn	O
++	O
+6	O
+.	O
+
+0	O
+29	O
+.	O
+5	O
+5	O
+.	O
+
+0	O
+6	O
+.	O
+
+5	O
+
+(	O
+C	O
+:	O
+G	O
+=	O
+5	O
+:	O
+1	O
+)	O
+.	O
+
+.	O
+
+Values	O
+given	O
+are	O
+relative	O
+to	O
+incorporation	O
+of	O
+[	O
+H	O
+]	O
+dTMP	O
+at	O
+pH	O
+7	O
+.	O
+
+8	O
+on	O
+activated	O
+DNA	O
+.	O
+
+For	O
+A2	O
+this	O
+was	O
+176	O
+.	O
+5	O
+pmol	O
+,	O
+for	O
+C	O
+232	O
+pmol	O
+.	O
+
+dATP	O
+,	O
+dCTP	O
+,	O
+dGTP	O
+and	O
+dTTP	O
+were	O
+included	O
+for	O
+assays	O
+using	O
+activated	O
+DNA	O
+,	O
+only	O
+the	O
+deoxynucleoside	O
+triphosphate	O
+stated	O
+was	O
+used	O
+in	O
+the	O
+synthetic	O
+template	O
+
+initiator	O
+complex	O
+assays	O
+.	O
+
+Assays	O
+were	O
+for	O
+10	O
+minutes	O
+.	O
+
+The	O
+buffers	O
+and	O
+concentrations	O
+of	O
+the	O
+divalent	O
+cations	O
+were	O
+as	O
+in	O
+Materials	O
+and	O
+Methods	O
+.	O
+
+this	O
+lag	O
+,	O
+but	O
+the	O
+annealing	O
+of	O
+template	O
+to	O
+initiator	O
+is	O
+only	O
+transient	O
+'	O
+and	O
+the	O
+DNA	O
+polymerase	O
+subunit	O
+may	O
+have	O
+difficulty	O
+in	O
+stabilising	O
+the	O
+complex	O
+and	O
+the	O
+50	O
+-	O
+70	O
+,	O
+000	O
+molecular	O
+weight	O
+subunit	O
+may	O
+be	O
+able	O
+to	O
+help	O
+the	O
+poly	O
+
+merase	O
+subunit	O
+to	O
+overcome	O
+this	O
+.	O
+
+Addition	O
+of	O
+the	O
+50	O
+-	O
+70	O
+,	O
+000	O
+subunit	O
+to	O
+the	O
+polymerase	O
+subunit	O
+prior	O
+to	O
+assaying	O
+with	O
+these	O
+templates	O
+had	O
+no	O
+effect	O
+on	O
+activity	O
+and	O
+it	O
+may	O
+be	O
+that	O
+a	O
+preincubation	O
+period	O
+is	O
+required	O
+before	O
+the	O
+two	O
+3350	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Figure	O
+4	O
+Activity	O
+of	O
+A2	O
+and	O
+C	O
+enzymes	O
+on	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+(	O
+dT	O
+)	O
+jO	O
+(	O
+A	O
+:	O
+T	O
+=	O
+
+20	O
+:	O
+1	O
+)	O
+as	O
+a	O
+function	O
+of	O
+time	O
+.	O
+
+50	O
+,	O
+ul	O
+samples	O
+were	O
+withdrawn	O
+at	O
+various	O
+times	O
+from	O
+a	O
+0	O
+.	O
+
+6	O
+inl	O
+incubation	O
+mix	O
+at	O
+30	O
+?	O
+C	O
+and	O
+added	O
+to	O
+0	O
+.	O
+
+5	O
+ml	O
+0	O
+.	O
+
+1	O
+M	O
+sodium	O
+
+pyrophosphate	O
+containing	O
+100	O
+,	O
+ug	O
+/	O
+ml	O
+native	O
+calf	B
+thymus	O
+DNA	O
+and	O
+processed	O
+for	O
+counting	O
+in	O
+the	O
+usual	O
+manner6	O
+.	O
+
+The	O
+mix	O
+contained	O
+1	O
+mM	O
+dithiothreitol	O
+,	O
+50	O
+mM	O
+tris	O
+HC1	O
+,	O
+pH	O
+7	O
+.	O
+8	O
+10	O
+mM	O
+MgC12	O
+,	O
+0	O
+.	O
+
+1	O
+mM	O
+[	O
+3H	O
+]	O
+dTTP	O
+(	O
+15	O
+cpm	O
+/	O
+pmol	O
+)	O
+,	O
+312	O
+.	O
+5	O
+,	O
+ug	O
+bovine	B
+serum	O
+albumin	O
+,	O
+5	O
+Fg	O
+poly	O
+(	O
+dA	O
+)	O
+.	O
+oligo	O
+(	O
+dT	O
+)	O
+(	O
+A	O
+:	O
+T	O
+=	O
+20	O
+:	O
+1	O
+)	O
+and	O
+enzyme	O
+protein	O
+(	O
+*	O
+-	O
+*	O
+)	O
+3	O
+.	O
+3	O
+units	O
+reconstituted	O
+A2	O
+,	O
+(	O
+o	O
+-	O
+o	O
+)	O
+16	O
+.	O
+
+0	O
+units	O
+urea	O
+derived	O
+C	O
+enzyme	O
+.	O
+
+subunits	O
+become	O
+fully	O
+associated	O
+.	O
+
+After	O
+the	O
+lag	O
+phase	O
+is	O
+over	O
+the	O
+C	O
+enzyme	O
+is	O
+still	O
+less	O
+active	O
+on	O
+these	O
+template	O
+-	O
+initiators	O
+than	O
+A	O
+enzyme	O
+.	O
+
+That	O
+is	O
+the	O
+A	O
+enzyme	O
+seems	O
+capable	O
+of	O
+elongating	O
+the	O
+initiator	O
+faster	O
+than	O
+the	O
+C	O
+enzyme	O
+.	O
+
+Experiments	O
+to	O
+determine	O
+whether	O
+the	O
+differences	O
+in	O
+rates	O
+of	O
+elongation	O
+of	O
+these	O
+template	O
+-	O
+initiator	O
+complexes	O
+are	O
+differences	O
+in	O
+processivity	O
+of	O
+the	O
+
+enzymes	O
+under	O
+the	O
+different	O
+pH	O
+and	O
+divalent	O
+cation	O
+conditions	O
+are	O
+under	O
+way	O
+.	O
+
+ACKNOWLEDGEMENTS	O
+
+We	O
+thank	O
+the	O
+Medical	O
+Research	O
+Council	O
+for	O
+a	O
+research	O
+grant	O
+.	O
+
+Communications	O
+concerning	O
+the	O
+paper	O
+should	O
+be	O
+sent	O
+to	O
+:	O
+
+Dr	O
+.	O
+A	O
+.	O
+
+M	O
+.	O
+
+Holmes	O
+,	O
+Department	O
+of	O
+Biochemistry	O
+,	O
+University	O
+of	O
+Strathclyde	O
+,	O
+The	O
+Todd	O
+Centre	O
+,	O
+31	O
+Taylor	O
+Street	O
+,	O
+Glasgow	O
+G4	O
+ONR	O
+,	O
+U	O
+.	O
+K	O
+.	O
+
+3351	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+REFERENCES	O
+
+(	O
+1	O
+)	O
+Bollum	O
+,	O
+F	O
+.	O
+J	O
+.	O
+
+(	O
+1975	O
+)	O
+.	O
+
+Prog	O
+.	O
+
+Nucleic	O
+Acid	O
+Res	O
+.	O
+
+Mol	O
+.	O
+
+Biol	O
+.	O
+
+15	O
+,	O
+
+109	O
+-	O
+144	O
+.	O
+
+(	O
+2	O
+)	O
+Holmes	O
+,	O
+A	O
+.	O
+M	O
+.	O
+,	O
+Hesslewood	O
+,	O
+I	O
+.	O
+P	O
+.	O
+and	O
+Johnston	O
+,	O
+I	O
+.	O
+R	O
+.	O
+
+(	O
+1976	O
+)	O
+.	O
+
+Eur	O
+.	O
+
+J	O
+.	O
+
+Biochem	O
+.	O
+
+62	O
+,	O
+229	O
+-	O
+235	O
+.	O
+
+(	O
+3	O
+)	O
+Matsukage	O
+,	O
+A	O
+.	O
+,	O
+Sivarajan	O
+,	O
+M	O
+.	O
+and	O
+Wilson	O
+,	O
+S	O
+.	O
+H	O
+.	O
+
+(	O
+1976	O
+)	O
+.	O
+
+Biochem	O
+
+istry	O
+15	O
+,	O
+5305	O
+-	O
+5314	O
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+(	O
+4	O
+)	O
+Fisher	O
+,	O
+P	O
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+Korn	O
+,	O
+D	O
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+
+(	O
+1977	O
+)	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+252	O
+,	O
+6528	O
+
+6535	O
+.	O
+
+(	O
+5	O
+)	O
+Fichot	O
+,	O
+O	O
+.	O
+,	O
+Pascal	O
+,	O
+M	O
+.	O
+,	O
+Mechali	O
+,	O
+M	O
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+De	O
+Recondo	O
+,	O
+A	O
+,	O
+-	O
+M	O
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+
+(	O
+1979	O
+)	O
+.	O
+
+Biochim	O
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+
+Biophys	O
+.	O
+
+Acta	O
+,	O
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+,	O
+28	O
+-	O
+41	O
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+(	O
+6	O
+)	O
+Holmes	O
+,	O
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+.	O
+M	O
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+,	O
+Hesslewood	O
+,	O
+I	O
+.	O
+R	O
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+Johnston	O
+,	O
+I	O
+.	O
+R	O
+.	O
+
+(	O
+1974	O
+)	O
+.	O
+
+Eur	O
+.	O
+
+J	O
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+
+Biochemn	O
+.	O
+
+43	O
+,	O
+487	O
+-	O
+499	O
+.	O
+
+(	O
+7	O
+)	O
+Noy	O
+,	O
+G	O
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+P	O
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+Weissbach	O
+,	O
+A	O
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+
+(	O
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+)	O
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+
+Biochim	O
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+
+Biophys	O
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+
+Acta	O
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+
+447	O
+,	O
+70	O
+-	O
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+
+(	O
+8	O
+)	O
+Craig	O
+,	O
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+Keir	O
+,	O
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+
+M	O
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+
+(	O
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+)	O
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+
+Biochem	O
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+
+J	O
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+
+145	O
+,	O
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+-	O
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+
+(	O
+9	O
+)	O
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+,	O
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+,	O
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+,	O
+E	O
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+(	O
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+Proc	O
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+
+Natl	O
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+Acad	O
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+
+Sci	O
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+U	O
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+
+71	O
+,	O
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+-	O
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+
+110	O
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+,	O
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+
+(	O
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+
+Eur	O
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+J	O
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+Biochem	O
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+
+50	O
+,	O
+
+357	O
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+
+(	O
+11	O
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+Blumenthal	O
+,	O
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+
+(	O
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+Biochemistry	O
+,	O
+16	O
+,	O
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+3137	O
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+(	O
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+,	O
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+,	O
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+,	O
+M	O
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+,	O
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+
+(	O
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+)	O
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+
+J	O
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+
+Biol	O
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+
+Chem	O
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+
+248	O
+,	O
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+
+(	O
+13	O
+)	O
+Yoshida	O
+,	O
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+,	O
+Konda	O
+,	O
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+Ando	O
+,	O
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+
+(	O
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+)	O
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+
+Biochim	O
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+
+Biophys	O
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+
+Acta	O
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+(	O
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+,	O
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+,	O
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+
+Johnston	O
+,	O
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+(	O
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+
+Biochem	O
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+42	O
+,	O
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+(	O
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+,	O
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+,	O
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+,	O
+P	O
+.	O
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+,	O
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+
+(	O
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+)	O
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+
+Biochim	O
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+
+Biophys	O
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+
+Acta	O
+,	O
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+(	O
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+,	O
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+,	O
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+,	O
+I	O
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+
+(	O
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+)	O
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+
+Nature	O
+(	O
+London	O
+)	O
+255	O
+,	O
+420	O
+-	O
+422	O
+.	O
+
+(	O
+17	O
+)	O
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+,	O
+F	O
+.	O
+
+J	O
+.	O
+
+(	O
+1966	O
+)	O
+.	O
+
+Procedures	O
+in	O
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+
+(	O
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+Davis	O
+,	O
+D	O
+.	O
+R	O
+.	O
+eds	O
+)	O
+.	O
+
+pp	O
+577	O
+-	O
+583	O
+,	O
+Harper	O
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+,	O
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+York	O
+.	O
+
+(	O
+18	O
+)	O
+Barrett	O
+,	O
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+.	O
+J	O
+.	O
+
+(	O
+1975	O
+)	O
+.	O
+
+Proteases	O
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+Control	O
+pp	O
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+-	O
+482	O
+,	O
+
+Cold	O
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+Laboratory	O
+,	O
+Cold	O
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+.	O
+
+(	O
+19	O
+)	O
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+,	O
+F	O
+.	O
+
+M	O
+.	O
+and	O
+Vithayathil	O
+,	O
+P	O
+.	O
+J	O
+.	O
+
+(	O
+1960	O
+)	O
+.	O
+
+Brookhaven	O
+Symp	O
+.	O
+
+Biol	O
+.	O
+
+13	O
+,	O
+115	O
+-	O
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+.	O
+
+(	O
+20	O
+)	O
+Lowe	O
+,	O
+P	O
+.	O
+A	O
+.	O
+,	O
+and	O
+Malcolm	O
+,	O
+A	O
+.	O
+B	O
+.	O
+D	O
+.	O
+
+(	O
+1976	O
+)	O
+.	O
+
+Eur	O
+.	O
+
+J	O
+.	O
+
+Biochem	O
+.	O
+
+64	O
+,	O
+
+177	O
+-	O
+188	O
+.	O
+
+(	O
+21	O
+)	O
+Hesslewood	O
+,	O
+I	O
+.	O
+P	O
+.	O
+,	O
+Holmes	O
+,	O
+A	O
+.	O
+M	O
+.	O
+,	O
+Wakeling	O
+,	O
+W	O
+.	O
+F	O
+.	O
+and	O
+Johnston	O
+,	O
+
+I	O
+.	O
+R	O
+.	O
+
+(	O
+1978	O
+)	O
+.	O
+
+Eur	O
+.	O
+
+J	O
+.	O
+
+Biochenr	O
+.	O
+.	O
+
+84	O
+,	O
+123	O
+-	O
+131	O
+.	O
+
+(	O
+22	O
+)	O
+Mechali	O
+,	O
+M	O
+.	O
+and	O
+De	O
+Recondo	O
+,	O
+A	O
+.	O
+
+-	O
+M	O
+.	O
+
+(	O
+1978	O
+)	O
+.	O
+
+Biochim	O
+.	O
+
+Biophys	O
+.	O
+
+Res	O
+.	O
+
+Comm	O
+,	O
+82	O
+,	O
+255	O
+-	O
+264	O
+.	O
+
+(	O
+23	O
+)	O
+Chang	O
+,	O
+L	O
+.	O
+M	O
+.	O
+S	O
+.	O
+,	O
+Cassani	O
+,	O
+G	O
+.	O
+R	O
+.	O
+and	O
+Bollum	O
+,	O
+F	O
+.	O
+J	O
+.	O
+
+(	O
+1972	O
+)	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Che	O
+.	O
+
+247	O
+,	O
+7718	O
+-	O
+7723	O
+.	O
+
+(	O
+24	O
+)	O
+Wickremasinghe	O
+,	O
+R	O
+.	O
+G	O
+.	O
+and	O
+Johnston	O
+,	O
+I	O
+.	O
+R	O
+.	O
+
+(	O
+1974	O
+)	O
+.	O
+
+Biochim	O
+.	O
+
+Biophys	O
+.	O
+
+Acta	O
+,	O
+361	O
+,	O
+37	O
+-	O
+52	O
+.	O
+
+3352	O
+
+Primitive	O
+Neuroectodermal	O
+Tumor	O
+(	O
+PNET	O
+)	O
+of	O
+the	O
+kidney	O
+:	O
+a	O
+case	O
+report	O
+
+Abstract	O
+
+Background	O
+
+A	O
+case	O
+of	O
+Primitive	O
+Neuroectodermal	O
+Tumor	O
+(	O
+PNET	O
+)	O
+of	O
+the	O
+kidney	O
+in	O
+a	O
+27	O
+-	O
+year	O
+-	O
+old	O
+woman	B
+is	O
+presented	O
+.	O
+
+Few	O
+cases	O
+are	O
+reported	O
+in	O
+the	O
+literature	O
+with	O
+a	O
+variable	O
+,	O
+nonspecific	O
+presentation	O
+and	O
+an	O
+aggressive	O
+behaviour	O
+.	O
+
+In	O
+our	O
+case	O
+,	O
+a	O
+radical	O
+nephrectomy	O
+with	O
+lymphadenectomy	O
+was	O
+performed	O
+and	O
+there	O
+was	O
+no	O
+residual	O
+or	O
+recurrent	O
+tumour	O
+at	O
+24	O
+-	O
+month	O
+follow	O
+-	O
+up	O
+.	O
+
+Methods	O
+
+The	O
+surgical	O
+specimens	O
+were	O
+formalin	O
+-	O
+fixed	O
+and	O
+paraffin	O
+embedded	O
+.	O
+
+The	O
+sections	O
+were	O
+stained	O
+with	O
+routinary	O
+H	O
+&	O
+E	O
+.	O
+
+Immunohistochemistry	O
+was	O
+performed	O
+.	O
+
+Results	O
+
+The	O
+immunohistochemical	O
+evaluation	O
+revealed	O
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+diffuse	O
+CD99	O
+positivity	O
+in	O
+the	O
+cytoplasm	O
+of	O
+the	O
+neoplastic	O
+cells	O
+.	O
+
+Pankeratin	O
+,	O
+cytokeratin	O
+AE1	O
+/	O
+AE3	O
+,	O
+vimentin	O
+,	O
+desmin	O
+,	O
+S100	O
+,	O
+cromogranin	O
+were	O
+negative	O
+.	O
+
+The	O
+clinical	O
+presentation	O
+and	O
+the	O
+macroscopic	O
+aspect	O
+,	O
+together	O
+with	O
+the	O
+histological	O
+pattern	O
+,	O
+the	O
+cytological	O
+characteristic	O
+and	O
+the	O
+cellular	O
+immunophenotype	O
+addressed	O
+the	O
+diagnosis	O
+towards	O
+primary	O
+PNET	O
+of	O
+kidney	O
+.	O
+
+Conclusions	O
+
+Since	O
+sometimes	O
+it	O
+is	O
+difficult	O
+to	O
+discriminate	O
+between	O
+PNET	O
+and	O
+Ewing	O
+'	O
+s	O
+tumour	O
+,	O
+we	O
+reviewed	O
+the	O
+difficulties	O
+in	O
+differential	O
+diagnosis	O
+.	O
+
+These	O
+tumors	O
+have	O
+a	O
+common	O
+precursor	O
+but	O
+the	O
+stage	O
+of	O
+differentiation	O
+in	O
+which	O
+it	O
+is	O
+blocked	O
+is	O
+probably	O
+different	O
+.	O
+
+This	O
+could	O
+also	O
+explain	O
+their	O
+different	O
+biological	O
+behaviour	O
+and	O
+prognosis	O
+.	O
+
+Background	O
+
+The	O
+peripheral	O
+Primitive	O
+Neuroectodermal	O
+Tumor	O
+(	O
+PNET	O
+)	O
+,	O
+firstly	O
+recognized	O
+by	O
+Arthur	O
+Purdy	O
+Stout	O
+in	O
+1918	O
+,	O
+is	O
+a	O
+member	O
+of	O
+the	O
+family	O
+of	O
+"	O
+small	O
+round	O
+-	O
+cell	O
+tumors	O
+"	O
+.	O
+
+Primitive	O
+renal	O
+localization	O
+is	O
+very	O
+rare	O
+.	O
+
+There	O
+are	O
+almost	O
+50	O
+cases	O
+reported	O
+in	O
+the	O
+literature	O
+,	O
+although	O
+it	O
+is	O
+difficult	O
+to	O
+estimate	O
+the	O
+exact	O
+number	O
+since	O
+often	O
+it	O
+has	O
+not	O
+been	O
+differentiated	O
+from	O
+Ewing	O
+'	O
+s	O
+Sarcoma	O
+[	O
+1	O
+-	O
+13	O
+]	O
+.	O
+
+Renal	O
+PNET	O
+is	O
+more	O
+aggressive	O
+than	O
+in	O
+the	O
+other	O
+sites	O
+.	O
+
+It	O
+frequently	O
+arises	O
+during	O
+childhood	O
+or	O
+adolescence	O
+,	O
+having	O
+an	O
+aggressive	O
+clinical	O
+course	O
+towards	O
+metastatic	O
+disease	O
+and	O
+death	O
+.	O
+
+It	O
+often	O
+recurs	O
+locally	O
+and	O
+metastasises	O
+early	O
+to	O
+regional	O
+lymph	O
+nodes	O
+,	O
+lungs	O
+,	O
+liver	O
+,	O
+bone	O
+and	O
+bone	O
+marrow	O
+,	O
+resulting	O
+in	O
+a	O
+poor	O
+prognosis	O
+.	O
+
+The	O
+5	O
+-	O
+year	O
+disease	O
+-	O
+free	O
+survival	O
+rate	O
+,	O
+for	O
+patients	B
+presenting	O
+well	O
+confined	O
+extra	O
+-	O
+skeletal	O
+PNET	O
+,	O
+is	O
+around	O
+45	O
+-	O
+55	O
+%	O
+and	O
+cases	O
+with	O
+advanced	O
+disease	O
+at	O
+presentation	O
+have	O
+a	O
+median	O
+relapse	O
+-	O
+free	O
+survival	O
+of	O
+only	O
+2	O
+years	O
+[	O
+1	O
+]	O
+.	O
+
+Case	O
+presentation	O
+
+A	O
+27	O
+-	O
+year	O
+-	O
+old	O
+woman	B
+was	O
+referred	O
+because	O
+of	O
+a	O
+mild	O
+left	O
+flank	O
+pain	O
+and	O
+haematuria	O
+.	O
+
+Ultrasonography	O
+identified	O
+a	O
+left	O
+renal	O
+mass	O
+homogeneously	O
+hyperechogenic	O
+in	O
+comparison	O
+with	O
+renal	O
+parenchyma	O
+.	O
+
+CT	O
+scan	O
+showed	O
+a	O
+11	O
+mm	O
+x	O
+8	O
+mm	O
+x	O
+6	O
+mm	O
+tumor	O
+replacing	O
+the	O
+upper	O
+half	O
+of	O
+the	O
+left	O
+kidney	O
+with	O
+extension	O
+into	O
+the	O
+renal	O
+vein	O
+.	O
+
+Chest	O
+x	O
+-	O
+ray	O
+was	O
+negative	O
+.	O
+
+Pathological	O
+stage	O
+after	O
+radical	O
+nephrectomy	O
+was	O
+T3aN0Mx	O
+.	O
+
+The	O
+surgical	O
+specimens	O
+were	O
+formalin	O
+-	O
+fixed	O
+and	O
+paraffin	O
+embedded	O
+.	O
+
+The	O
+sections	O
+were	O
+stained	O
+with	O
+routinary	O
+H	O
+&	O
+E	O
+.	O
+
+Immunohistochemistry	O
+was	O
+performed	O
+using	O
+avidin	O
+biotin	O
+complex	O
+technique	O
+and	O
+diaminobenzidine	O
+as	O
+chromogen	O
+.	O
+
+The	O
+antibodies	O
+used	O
+included	O
+CD99	O
+(	O
+Dako	O
+,	O
+M3601	O
+)	O
+,	O
+pankeratin	O
+(	O
+Dako	O
+,	O
+M0821	O
+)	O
+,	O
+cytokeratin	O
+AE1	O
+/	O
+AE3	O
+(	O
+Dako	O
+,	O
+M3515	O
+)	O
+,	O
+vimentin	O
+(	O
+Dako	O
+,	O
+M7010	O
+)	O
+,	O
+desmin	O
+(	O
+Dako	O
+,	O
+M0760	O
+)	O
+,	O
+S100	O
+(	O
+Dako	O
+,	O
+Z0311	O
+)	O
+,	O
+and	O
+chromogranin	O
+A	O
+(	O
+Dako	O
+,	O
+M0869	O
+)	O
+,	O
+at	O
+suggested	O
+dilution	O
+.	O
+
+We	O
+performed	O
+also	O
+appropriate	O
+routinely	O
+positive	O
+and	O
+negative	O
+controls	O
+.	O
+
+The	O
+tumor	O
+was	O
+multilobular	O
+,	O
+grey	O
+,	O
+glistening	O
+,	O
+focally	O
+hemorrhagic	O
+,	O
+surrounded	O
+by	O
+a	O
+capsule	O
+and	O
+with	O
+a	O
+sharp	O
+demarcation	O
+from	O
+the	O
+uninvolved	O
+kidney	O
+.	O
+
+Histologically	O
+,	O
+the	O
+tumor	O
+consisted	O
+of	O
+small	O
+round	O
+cells	O
+with	O
+round	O
+nuclei	O
+and	O
+scant	O
+cytoplasm	O
+.	O
+
+It	O
+presented	O
+different	O
+patterns	O
+,	O
+with	O
+cohesive	O
+lobules	O
+or	O
+rosettes	O
+and	O
+perivascular	O
+pseudo	O
+-	O
+rosettes	O
+or	O
+,	O
+in	O
+some	O
+areas	O
+,	O
+spindle	O
+cellular	O
+elements	O
+(	O
+fig	O
+.	O
+1	O
+)	O
+.	O
+
+The	O
+immunohistochemical	O
+evaluation	O
+revealed	O
+a	O
+diffuse	O
+CD99	O
+positivity	O
+in	O
+the	O
+cytoplasm	O
+of	O
+the	O
+neoplastic	O
+cells	O
+(	O
+fig	O
+.	O
+2	O
+)	O
+;	O
+tumoral	O
+cells	O
+were	O
+also	O
+visible	O
+in	O
+the	O
+vascular	O
+lumens	O
+(	O
+fig	O
+.	O
+3	O
+)	O
+.	O
+
+By	O
+contrast	O
+,	O
+pankeratin	O
+,	O
+cytokeratin	O
+AE1	O
+/	O
+AE3	O
+,	O
+vimentin	O
+,	O
+desmin	O
+,	O
+S100	O
+,	O
+cromogranin	O
+were	O
+negative	O
+.	O
+
+The	O
+clinical	O
+presentation	O
+and	O
+the	O
+macroscopic	O
+aspect	O
+,	O
+together	O
+with	O
+the	O
+histological	O
+pattern	O
+,	O
+the	O
+cytological	O
+characteristic	O
+and	O
+the	O
+cellular	O
+immunophenotype	O
+addressed	O
+the	O
+diagnosis	O
+towards	O
+primary	O
+PNET	O
+of	O
+kidney	O
+.	O
+
+A	O
+bone	O
+scan	O
+did	O
+not	O
+reveal	O
+positive	O
+areas	O
+.	O
+
+Eight	O
+cycles	O
+of	O
+chemotherapy	O
+with	O
+Vincristine	O
+,	O
+Ifosfamide	O
+and	O
+Adriamycin	O
+,	O
+four	O
+cycles	O
+of	O
+Ifosfamide	O
+and	O
+VP16	O
+and	O
+eight	O
+sittings	O
+of	O
+local	O
+radiotherapy	O
+were	O
+sequentially	O
+performed	O
+.	O
+
+Follow	O
+-	O
+up	O
+examinations	O
+with	O
+CT	O
+and	O
+bone	O
+scan	O
+failed	O
+to	O
+show	O
+residual	O
+or	O
+recurrent	O
+tumor	O
+after	O
+24	O
+months	O
+.	O
+
+Conclusions	O
+
+Primitive	O
+Neuroectodermal	O
+Tumor	O
+of	O
+the	O
+kidney	O
+is	O
+a	O
+rare	O
+entity	O
+.	O
+
+The	O
+few	O
+cases	O
+reported	O
+revealed	O
+a	O
+variable	O
+presentation	O
+and	O
+an	O
+aggressive	O
+behaviour	O
+.	O
+
+The	O
+distinction	O
+from	O
+other	O
+primary	O
+malignancies	O
+of	O
+the	O
+kidneys	O
+is	O
+crucial	O
+for	O
+prognosis	O
+.	O
+
+The	O
+differential	O
+diagnosis	O
+includes	O
+extra	O
+-	O
+osseous	O
+Ewing	O
+'	O
+s	O
+sarcoma	O
+,	O
+rhabdomyosarcoma	O
+,	O
+Wilm	O
+'	O
+s	O
+tumor	O
+,	O
+carcinoid	O
+,	O
+neuroblastoma	O
+,	O
+clear	O
+cell	O
+sarcoma	O
+of	O
+the	O
+kidney	O
+,	O
+lymphoma	O
+,	O
+the	O
+small	O
+cell	O
+variant	O
+of	O
+osteosarcoma	O
+,	O
+desmoplastic	O
+small	O
+round	O
+cell	O
+tumor	O
+and	O
+nephroblastoma	O
+[	O
+5	O
+]	O
+.	O
+
+The	O
+Homer	O
+-	O
+Wright	O
+type	O
+rosettes	O
+,	O
+commonly	O
+scarce	O
+of	O
+number	O
+or	O
+less	O
+defined	O
+in	O
+extra	O
+skeletal	O
+Ewing	O
+'	O
+s	O
+sarcoma	O
+(	O
+ES	O
+)	O
+,	O
+are	O
+a	O
+typical	O
+histological	O
+feature	O
+for	O
+PNET	O
+and	O
+can	O
+address	O
+the	O
+diagnosis	O
+although	O
+they	O
+can	O
+be	O
+found	O
+also	O
+in	O
+neuroblastoma	O
+[	O
+5	O
+]	O
+.	O
+
+To	O
+better	O
+address	O
+the	O
+diagnosis	O
+,	O
+an	O
+immunohistochemical	O
+analysis	O
+is	O
+necessary	O
+.	O
+
+In	O
+our	O
+case	O
+the	O
+presence	O
+of	O
+MIC	O
+-	O
+2	O
+gene	O
+products	O
+,	O
+known	O
+also	O
+as	O
+CD99	O
+,	O
+12E7	O
+,	O
+E2	O
+,	O
+013	O
+and	O
+HBA71	O
+,	O
+suggested	O
+a	O
+PNET	O
+diagnosis	O
+.	O
+
+Primitive	O
+neuroectodermal	O
+tumors	O
+only	O
+immunorreactive	O
+to	O
+CD99	O
+,	O
+even	O
+if	O
+uncommon	O
+,	O
+are	O
+reported	O
+in	O
+the	O
+literature	O
+[	O
+13	O
+]	O
+.	O
+
+The	O
+reactivity	O
+to	O
+vimentin	O
+,	O
+NSE	O
+and	O
+S	O
+-	O
+100	O
+may	O
+facilitate	O
+the	O
+diagnosis	O
+but	O
+is	O
+not	O
+patognomonic	O
+,	O
+while	O
+CD	O
+99	O
+positivity	O
+is	O
+nowadays	O
+a	O
+clue	O
+for	O
+the	O
+diagnosis	O
+.	O
+
+Moreover	O
+cytogenetic	O
+studies	O
+(	O
+not	O
+performed	O
+in	O
+our	O
+case	O
+)	O
+demonstrated	O
+that	O
+PNET	O
+and	O
+Ewing	O
+'	O
+s	O
+sarcoma	O
+can	O
+both	O
+be	O
+associated	O
+to	O
+a	O
+translocation	O
+of	O
+the	O
+long	O
+arms	O
+of	O
+chromosome	O
+11	O
+and	O
+22	O
+,	O
+t	O
+(	O
+11	O
+;	O
+22	O
+)	O
+(	O
+q22	O
+;	O
+q12	O
+)	O
+[	O
+5	O
+]	O
+.	O
+
+Despite	O
+their	O
+genetic	O
+and	O
+antigenic	O
+similarity	O
+,	O
+many	O
+authors	O
+currently	O
+recognize	O
+PNET	O
+and	O
+extra	O
+-	O
+skeletal	O
+Ewing	O
+'	O
+s	O
+sarcoma	O
+of	O
+the	O
+kidney	O
+as	O
+separate	O
+entities	O
+.	O
+
+It	O
+is	O
+also	O
+important	O
+to	O
+keep	O
+separate	O
+renal	O
+PNET	O
+and	O
+malignant	O
+rhabdomyosarcoma	O
+tumor	O
+(	O
+MRT	O
+)	O
+.	O
+
+Weeks	O
+et	O
+al	O
+reported	O
+8	O
+cases	O
+suggestive	O
+for	O
+PNET	O
+but	O
+mimicking	O
+MRT	O
+[	O
+14	O
+]	O
+.	O
+
+Although	O
+renal	O
+PNET	O
+and	O
+MRT	O
+show	O
+similar	O
+clinico	O
+-	O
+pathological	O
+features	O
+,	O
+the	O
+latter	O
+usually	O
+occurs	O
+in	O
+very	O
+young	O
+children	O
+,	O
+having	O
+a	O
+more	O
+aggressive	O
+prognosis	O
+.	O
+
+Rodriguez	O
+et	O
+al	O
+postulated	O
+that	O
+these	O
+two	O
+renal	O
+neoplasms	O
+share	O
+a	O
+common	O
+undifferentiated	O
+precursor	O
+to	O
+explain	O
+their	O
+similarity	O
+and	O
+we	O
+agree	O
+with	O
+these	O
+Authors	O
+[	O
+12	O
+]	O
+.	O
+
+Indeed	O
+,	O
+the	O
+hypothesis	O
+that	O
+tumors	O
+arise	O
+from	O
+stem	O
+cells	O
+(	O
+SCs	O
+)	O
+as	O
+a	O
+consequence	O
+of	O
+a	O
+maturative	O
+arrest	O
+is	O
+now	O
+growing	O
+[	O
+15	O
+]	O
+.	O
+
+SCs	O
+are	O
+present	O
+in	O
+almost	O
+all	O
+tissues	O
+and	O
+may	O
+originate	O
+different	O
+cellular	O
+lineages	O
+by	O
+the	O
+multi	O
+-	O
+step	O
+process	O
+named	O
+"	O
+differentiation	O
+"	O
+.	O
+
+The	O
+role	O
+of	O
+SCs	O
+in	O
+tumorigenesis	O
+was	O
+clearly	O
+demonstrated	O
+in	O
+a	O
+number	O
+of	O
+carcinogenic	O
+models	O
+showing	O
+that	O
+solid	O
+and	O
+haematopoietic	O
+cancers	O
+could	O
+arise	O
+from	O
+tissue	O
+-	O
+specific	O
+SCs	O
+[	O
+16	O
+-	O
+19	O
+]	O
+.	O
+
+In	O
+agreement	O
+with	O
+Sell	O
+and	O
+Pierce	O
+,	O
+we	O
+retain	O
+that	O
+the	O
+degree	O
+of	O
+malignancy	O
+of	O
+a	O
+carcinoma	O
+depends	O
+by	O
+the	O
+stage	O
+in	O
+which	O
+SCs	O
+differentiation	O
+stopped	O
+during	O
+carcinogenesis	O
+[	O
+19	O
+]	O
+.	O
+
+In	O
+particular	O
+,	O
+since	O
+PNET	O
+,	O
+Ewing	O
+'	O
+s	O
+tumour	O
+and	O
+MRT	O
+have	O
+a	O
+similar	O
+morphology	O
+,	O
+our	O
+hypothesis	O
+is	O
+that	O
+the	O
+mesenchimal	O
+stem	O
+precursor	O
+of	O
+these	O
+tumors	O
+is	O
+the	O
+same	O
+,	O
+but	O
+the	O
+stage	O
+of	O
+differentiation	O
+in	O
+which	O
+it	O
+is	O
+blocked	O
+is	O
+different	O
+.	O
+
+This	O
+could	O
+explain	O
+why	O
+sometimes	O
+it	O
+is	O
+difficult	O
+to	O
+discriminate	O
+between	O
+these	O
+tumors	O
+,	O
+notwithstanding	O
+they	O
+present	O
+a	O
+different	O
+biological	O
+behaviour	O
+.	O
+
+Competing	O
+interests	O
+
+None	O
+declared	O
+.	O
+
+Authors	O
+'	O
+contribution	O
+
+All	O
+authors	O
+contributed	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+
+The	O
+c1	O
+genes	O
+of	O
+P1	O
+and	O
+P7	O
+.	O
+
+Abstract	O
+
+The	O
+c1	O
+genes	O
+of	O
+the	O
+heteroimmune	O
+phages	O
+P1	O
+and	O
+P7	O
+were	O
+sequenced	O
+and	O
+their	O
+products	O
+were	O
+compared	O
+.	O
+
+P7c1	O
+expression	O
+was	O
+correlated	O
+with	O
+the	O
+translation	O
+in	O
+vitro	O
+of	O
+a	O
+protein	O
+whose	O
+predicted	O
+molecular	O
+weight	O
+(	O
+33	O
+,	O
+000	O
+daltons	O
+)	O
+is	O
+indistinguishable	O
+from	O
+that	O
+of	O
+the	O
+P1c1	O
+repressor	O
+.	O
+
+The	O
+c1	O
+regions	O
+from	O
+both	O
+P1	O
+and	O
+P7	O
+were	O
+found	O
+to	O
+contain	O
+open	O
+reading	O
+frames	O
+capable	O
+of	O
+coding	O
+for	O
+a	O
+283	O
+-	O
+amino	O
+acid	O
+protein	O
+whose	O
+predicted	O
+secondary	O
+structure	O
+lacks	O
+the	O
+helix	O
+-	O
+turn	O
+-	O
+helix	O
+motif	O
+commonly	O
+associated	O
+with	O
+repressor	O
+proteins	O
+.	O
+
+Two	O
+P1c1	O
+amber	O
+mutations	O
+were	O
+localized	O
+to	O
+the	O
+283	O
+-	O
+amino	O
+acid	O
+open	O
+reading	O
+frame	O
+.	O
+
+The	O
+P1c1	O
+and	O
+P7c1	O
+sequences	O
+were	O
+found	O
+to	O
+differ	O
+at	O
+only	O
+18	O
+positions	O
+,	O
+all	O
+but	O
+two	O
+of	O
+which	O
+alter	O
+the	O
+third	O
+position	O
+of	O
+the	O
+affected	O
+codon	O
+and	O
+do	O
+not	O
+alter	O
+the	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+protein	O
+.	O
+
+Plasmids	O
+expressing	O
+the	O
+c1	O
+gene	O
+from	O
+either	O
+phage	O
+cause	O
+the	O
+repression	O
+of	O
+transcription	O
+from	O
+a	O
+cloned	O
+promoter	O
+situated	O
+upstream	O
+of	O
+P1c1	O
+.	O
+Images	O
+
+Volme	O
+7	O
+Nmbe	O
+19198	O
+Nulei	O
+Acds	O
+eserc	O
+
+The	O
+cl	O
+genes	O
+of	O
+P1	O
+and	O
+P7	O
+
+Francis	O
+A	O
+.	O
+Osborne	O
+,	O
+Sonja	O
+R	O
+.	O
+Stovall	O
+and	O
+Barbara	O
+R	O
+.	O
+Baumstark	O
+*	O
+
+Department	O
+of	O
+Biology	O
+,	O
+Georgia	O
+State	O
+University	O
+,	O
+Atlanta	O
+,	O
+GA	O
+30303	O
+,	O
+USA	O
+
+Received	O
+July	O
+11	O
+,	O
+1989	O
+;	O
+Revised	O
+and	O
+Accepted	O
+August	O
+29	O
+,	O
+1989	O
+EMBL	O
+accession	O
+nos	O
+X16005	O
+,	O
+X16006	O
+
+ABSTRACT	O
+
+The	O
+cl	O
+genes	O
+of	O
+the	O
+heteroimmune	O
+phages	O
+P1	O
+and	O
+P7	O
+were	O
+sequenced	O
+and	O
+their	O
+products	O
+were	O
+compared	O
+.	O
+
+P7cl	O
+expression	O
+was	O
+correlated	O
+with	O
+the	O
+translation	O
+in	O
+vitro	O
+of	O
+a	O
+protein	O
+whose	O
+predicted	O
+molecular	O
+weight	O
+(	O
+33	O
+,	O
+000	O
+daltons	O
+)	O
+is	O
+indistinguishable	O
+from	O
+that	O
+of	O
+the	O
+Plcl	O
+repressor	O
+.	O
+
+The	O
+cl	O
+regions	O
+from	O
+both	O
+P1	O
+and	O
+P7	O
+were	O
+found	O
+to	O
+contain	O
+open	O
+reading	O
+frames	O
+capable	O
+of	O
+coding	O
+for	O
+a	O
+283	O
+-	O
+amino	O
+acid	O
+protein	O
+whose	O
+predicted	O
+secondary	O
+structure	O
+lacks	O
+the	O
+helix	O
+-	O
+tum	O
+-	O
+helix	O
+motif	O
+commonly	O
+associated	O
+with	O
+repressor	O
+proteins	O
+.	O
+
+Two	O
+Plcl	O
+amber	O
+mutations	O
+were	O
+localized	O
+to	O
+the	O
+283	O
+-	O
+amino	O
+acid	O
+open	O
+reading	O
+frame	O
+.	O
+
+The	O
+Plcl	O
+and	O
+P7cl	O
+sequences	O
+were	O
+found	O
+to	O
+differ	O
+at	O
+only	O
+18	O
+positions	O
+,	O
+all	O
+but	O
+two	O
+of	O
+which	O
+alter	O
+the	O
+third	O
+position	O
+of	O
+the	O
+affected	O
+codon	O
+and	O
+do	O
+not	O
+alter	O
+the	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+protein	O
+.	O
+
+Plasmids	O
+expressing	O
+the	O
+cI	O
+gene	O
+from	O
+either	O
+phage	O
+cause	O
+the	O
+repression	O
+of	O
+transcription	O
+from	O
+a	O
+cloned	O
+promoter	O
+situated	O
+upstream	O
+of	O
+Plcl	O
+.	O
+
+INTRODUCTION	O
+
+The	O
+cl	O
+genes	O
+of	O
+the	O
+plasmid	O
+prophages	O
+P1	O
+and	O
+P7	O
+code	O
+for	O
+repressor	O
+proteins	O
+that	O
+are	O
+required	O
+for	O
+the	O
+establishment	O
+and	O
+maintenance	O
+of	O
+lysogeny	O
+(	O
+reviewed	O
+in	O
+1	O
+)	O
+.	O
+
+A	O
+protein	O
+corresponding	O
+to	O
+the	O
+Plcl	O
+repressor	O
+has	O
+been	O
+isolated	O
+and	O
+shown	O
+to	O
+be	O
+a	O
+sequence	O
+-	O
+specific	O
+DNA	O
+binding	O
+protein	O
+that	O
+recognizes	O
+several	O
+widely	O
+dispersed	O
+sites	O
+on	O
+the	O
+phage	O
+DNA	O
+(	O
+2	O
+-	O
+7	O
+)	O
+.	O
+
+The	O
+consensus	O
+DNA	O
+sequence	O
+recognized	O
+by	O
+the	O
+Plcl	O
+repressor	O
+(	O
+ATTTATTAGAGCA	O
+[	O
+A	O
+/	O
+T	O
+]	O
+T	O
+)	O
+contains	O
+no	O
+discernable	O
+bilateral	O
+symmetry	O
+,	O
+a	O
+feature	O
+that	O
+is	O
+highly	O
+unusual	O
+among	O
+prokaryotic	O
+operator	O
+sites	O
+.	O
+
+P1	O
+and	O
+P7	O
+are	O
+heteroimmune	O
+;	O
+that	O
+is	O
+,	O
+each	O
+phage	O
+is	O
+able	O
+to	O
+establish	O
+a	O
+lytic	O
+infection	O
+on	O
+a	O
+lysogen	O
+of	O
+the	O
+other	O
+phage	O
+.	O
+
+In	O
+this	O
+sense	O
+,	O
+their	O
+relationship	O
+is	O
+analogous	O
+to	O
+that	O
+of	O
+phage	O
+X	O
+and	O
+434	O
+,	O
+which	O
+differ	O
+in	O
+the	O
+DNA	O
+specificity	O
+of	O
+their	O
+cI	O
+repressor	O
+proteins	O
+(	O
+8	O
+)	O
+.	O
+
+However	O
+,	O
+genetic	O
+studies	O
+indicate	O
+that	O
+Plcl	O
+and	O
+P7cl	O
+can	O
+be	O
+crossed	O
+into	O
+the	O
+heterologous	O
+phage	O
+without	O
+affecting	O
+the	O
+immunity	O
+specificity	O
+of	O
+the	O
+recipient	O
+(	O
+9	O
+)	O
+.	O
+
+The	O
+basis	O
+for	O
+P1	O
+/	O
+P7	O
+heteroimmunity	O
+has	O
+been	O
+localized	O
+to	O
+a	O
+second	O
+regulatory	O
+gene	O
+,	O
+c4	O
+,	O
+that	O
+is	O
+unlinked	O
+to	O
+cl	O
+.	O
+
+The	O
+c4	O
+gene	O
+products	O
+prevent	O
+the	O
+expression	O
+of	O
+antireb	O
+,	O
+a	O
+closely	O
+linked	O
+gene	O
+that	O
+interferes	O
+with	O
+cl	O
+-	O
+mediated	O
+repression	O
+(	O
+10	O
+,	O
+11	O
+)	O
+.	O
+
+According	O
+to	O
+current	O
+models	O
+,	O
+P1	O
+/	O
+P7	O
+heteroimmunity	O
+results	O
+from	O
+the	O
+inability	O
+of	O
+the	O
+c4	O
+repressor	O
+of	O
+one	O
+phage	O
+to	O
+prevent	O
+antireb	O
+expression	O
+from	O
+the	O
+heteroimmune	O
+phage	O
+genome	O
+(	O
+10	O
+,	O
+11	O
+)	O
+.	O
+
+Because	O
+the	O
+cl	O
+genes	O
+of	O
+P1	O
+and	O
+P7	O
+are	O
+genetically	O
+interchangeable	O
+,	O
+it	O
+is	O
+anticipated	O
+that	O
+the	O
+two	O
+gene	O
+products	O
+carry	O
+out	O
+similar	O
+or	O
+identical	O
+regulatory	O
+functions	O
+.	O
+
+The	O
+studies	O
+presented	O
+in	O
+this	O
+paper	O
+were	O
+undertaken	O
+to	O
+investigate	O
+the	O
+biochemical	O
+basis	O
+for	O
+the	O
+apparent	O
+genetic	O
+identity	O
+of	O
+the	O
+two	O
+cl	O
+genes	O
+.	O
+
+In	O
+this	O
+paper	O
+,	O
+we	O
+present	O
+the	O
+DNA	O
+sequence	O
+of	O
+the	O
+cl	O
+genes	O
+of	O
+P1	O
+and	O
+P7	O
+and	O
+the	O
+predicted	O
+amino	O
+acid	O
+sequence	O
+of	O
+the	O
+cl	O
+repressor	O
+proteins	O
+.	O
+
+We	O
+report	O
+that	O
+Plcl	O
+and	O
+P7cl	O
+code	O
+for	O
+proteins	O
+of	O
+identical	O
+size	O
+(	O
+283	O
+amino	O
+acids	O
+)	O
+and	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Volume	O
+17	O
+Number	O
+19	O
+1989	O
+
+767	O
+1	O
+
+(	O
+r	O
+IRL	O
+Press	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+nearly	O
+identical	O
+sequence	O
+.	O
+
+We	O
+report	O
+further	O
+that	O
+both	O
+repressors	O
+prevent	O
+the	O
+expression	O
+of	O
+a	O
+promoter	O
+located	O
+immediately	O
+upstream	O
+of	O
+the	O
+Plc	O
+1	O
+open	O
+reading	O
+frame	O
+,	O
+an	O
+observation	O
+that	O
+confirms	O
+their	O
+functional	O
+similarity	O
+and	O
+suggests	O
+an	O
+autoregulatory	O
+role	O
+for	O
+the	O
+two	O
+proteins	O
+.	O
+
+Analysis	O
+of	O
+the	O
+secondary	O
+structure	O
+predicted	O
+by	O
+the	O
+open	O
+reading	O
+frames	O
+does	O
+not	O
+reveal	O
+the	O
+characteristic	O
+helix	O
+-	O
+turn	O
+-	O
+helix	O
+(	O
+12	O
+)	O
+or	O
+other	O
+motifs	O
+commonly	O
+associated	O
+with	O
+DNA	O
+binding	O
+proteins	O
+.	O
+
+MATERIALS	O
+AND	O
+METHODS	O
+Bacterial	O
+and	O
+phage	O
+strains	O
+.	O
+
+E	B
+.	I
+coli	I
+K336	O
+is	O
+a	O
+SuO	O
+derivative	O
+of	O
+K140	O
+(	O
+13	O
+)	O
+.	O
+
+E	B
+.	I
+coli	I
+CB454	O
+is	O
+a	O
+recA	O
+-	O
+,	O
+lacZderivative	O
+of	O
+K	O
+-	O
+12	O
+(	O
+14	O
+)	O
+.	O
+
+P1	O
++	O
+is	O
+described	O
+by	O
+Scott	O
+(	O
+13	O
+)	O
+.	O
+
+P7	O
++	O
+is	O
+the	O
+strain	O
+of	O
+Smith	O
+(	O
+15	O
+)	O
+,	O
+as	O
+described	O
+by	O
+Scott	O
+(	O
+16	O
+)	O
+.	O
+
+P7cl	O
+.	O
+
+1	O
+contains	O
+a	O
+missense	O
+mutation	O
+in	O
+the	O
+cl	O
+gene	O
+(	O
+17	O
+)	O
+.	O
+
+The	O
+P7	O
+phage	O
+strains	O
+and	O
+the	O
+cl	O
+amber	O
+mutant	O
+phage	O
+strains	O
+PIci	O
+.	O
+245Cm	O
+,	O
+Plc1	O
+.	O
+
+169	O
+and	O
+P	O
+Ic	O
+.	O
+55	O
+(	O
+11	O
+)	O
+were	O
+generously	O
+provided	O
+by	O
+June	O
+Scott	O
+.	O
+
+Enzymes	O
+and	O
+reagents	O
+.	O
+
+Restriction	O
+enzymes	O
+,	O
+T4	O
+DNA	O
+ligase	O
+and	O
+polymerase	O
+,	O
+and	O
+the	O
+Klenow	O
+fragment	O
+of	O
+E	B
+.	I
+coli	I
+DNA	O
+polymerase	O
+were	O
+purchased	O
+from	O
+Boehringer	O
+Biochemicals	O
+or	O
+New	O
+England	O
+Biolabs	O
+and	O
+reactions	O
+were	O
+carried	O
+out	O
+according	O
+to	O
+the	O
+manufacturers	O
+'	O
+instructions	O
+.	O
+
+DNA	O
+sequencing	O
+kits	O
+and	O
+in	O
+vitro	O
+transcription	O
+-	O
+translation	O
+kits	O
+were	O
+purchased	O
+from	O
+Bethesda	O
+Research	O
+Laboratories	O
+and	O
+Amersham	O
+Corporation	O
+,	O
+respectively	O
+.	O
+
+Synthetic	O
+oligonucleotides	O
+to	O
+be	O
+used	O
+as	O
+sequencing	O
+primers	O
+were	O
+prepared	O
+on	O
+an	O
+Applied	O
+Biosystems	O
+DNA	O
+synthesizer	O
+.	O
+
+Plasmid	O
+construction	O
+.	O
+
+pBRB7	O
+.	O
+2	O
+.	O
+
+pBRB7	O
+.	O
+2	O
+(	O
+2	O
+)	O
+contains	O
+a	O
+3	O
+.	O
+2	O
+kb	O
+EcoRI	O
+/	O
+PvuII	O
+fragment	O
+from	O
+the	O
+cl	O
+region	O
+of	O
+P1	O
+(	O
+Figure	O
+1	O
+)	O
+inserted	O
+into	O
+the	O
+2	O
+.	O
+3	O
+kb	O
+EcoRIlPvuII	O
+fragment	O
+of	O
+pBR322	O
+that	O
+contains	O
+the	O
+origin	O
+of	O
+replication	O
+and	O
+the	O
+f3	O
+-	O
+lactamase	O
+gene	O
+.	O
+
+pFA02	O
+.	O
+
+P7	O
+plasmid	O
+DNA	O
+was	O
+digested	O
+with	O
+PvuII	O
+,	O
+ligated	O
+to	O
+similarly	O
+digested	O
+pBR322	O
+,	O
+and	O
+transformed	O
+into	O
+E	B
+.	I
+coli	I
+K336	O
+.	O
+
+Ampicillin	O
+-	O
+resistant	O
+colonies	O
+were	O
+screened	O
+for	O
+cl	O
+activity	O
+by	O
+cross	O
+-	O
+streak	O
+complementation	O
+analysis	O
+against	O
+P7cl	O
+.	O
+1	O
+(	O
+18	O
+)	O
+.	O
+
+pFAO2	O
+contains	O
+a	O
+3	O
+.	O
+5	O
+kb	O
+insert	O
+of	O
+P7	O
+DNA	O
+.	O
+
+The	O
+fragment	O
+was	O
+localized	O
+to	O
+the	O
+cl	O
+region	O
+of	O
+the	O
+P7	O
+genome	O
+by	O
+Southern	O
+hybridization	O
+against	O
+P1	O
+and	O
+P7	O
+DNA	O
+that	O
+had	O
+been	O
+digested	O
+with	O
+BamHI	O
+and	O
+BglII	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+.	O
+
+pBRBJ69	O
+.	O
+
+1	O
+and	O
+pBRB55	O
+.	O
+
+1	O
+.	O
+
+The	O
+PI	O
+cI	O
+open	O
+reading	O
+frame	O
+was	O
+previously	O
+localized	O
+to	O
+a	O
+2	O
+.	O
+6	O
+kb	O
+EcoRlIBamHI	O
+fragment	O
+derived	O
+from	O
+PlEcoRI	O
+-	O
+7	O
+(	O
+2	O
+)	O
+.	O
+
+This	O
+fragment	O
+also	O
+contains	O
+the	O
+wildtype	O
+allele	O
+for	O
+the	O
+conditional	O
+lethal	O
+mutation	O
+am43	O
+(	O
+19	O
+,	O
+20	O
+)	O
+.	O
+
+To	O
+clone	O
+the	O
+cl	O
+reading	O
+frame	O
+from	O
+the	O
+amber	O
+mutant	O
+phage	O
+Plc1	O
+.	O
+169	O
+and	O
+P	O
+Ic	O
+.	O
+55	O
+,	O
+we	O
+digested	O
+phage	O
+DNA	O
+with	O
+EcoRI	O
+and	O
+BamHI	O
+,	O
+ligated	O
+the	O
+digestion	O
+products	O
+into	O
+similarly	O
+digested	O
+pBR322	O
+,	O
+and	O
+transformed	O
+the	O
+ligation	O
+mixture	O
+into	O
+E	B
+.	I
+coli	I
+K336	O
+.	O
+
+Ampicillin	O
+-	O
+resistant	O
+,	O
+tetracyclinesensitiv	O
+colonies	O
+were	O
+screened	O
+by	O
+cross	O
+-	O
+streak	O
+complementation	O
+analysis	O
+for	O
+their	O
+ability	O
+to	O
+support	O
+the	O
+growth	O
+of	O
+Plam43	O
+.	O
+
+Plasmid	O
+DNA	O
+isolated	O
+from	O
+complementation	O
+-	O
+positive	O
+cells	O
+was	O
+shown	O
+by	O
+agarose	O
+gel	O
+electrophoresis	O
+to	O
+carry	O
+plasmids	O
+containing	O
+the	O
+2	O
+.	O
+6	O
+kb	O
+EcoRIlBamHI	O
+fragment	O
+from	O
+the	O
+cl	O
+region	O
+.	O
+
+The	O
+cl	O
+mutant	O
+open	O
+reading	O
+frames	O
+were	O
+placed	O
+under	O
+the	O
+control	O
+of	O
+normal	O
+regulatory	O
+signals	O
+present	O
+in	O
+the	O
+cI	O
+region	O
+by	O
+digesting	O
+the	O
+cl	O
+.	O
+55	O
+and	O
+cl	O
+.	O
+
+169	O
+-	O
+containing	O
+plasmids	O
+with	O
+BamHI	O
+and	O
+PvuII	O
+and	O
+inserting	O
+a	O
+601	O
+bp	O
+BamHI	O
+/	O
+PvuH	O
+fragment	O
+containing	O
+the	O
+cl	O
+promoter	O
+region	O
+(	O
+2	O
+)	O
+.	O
+
+The	O
+resulting	O
+plasmids	O
+,	O
+pBRB55	O
+.	O
+1	O
+and	O
+pBRB169	O
+.	O
+1	O
+,	O
+respectively	O
+,	O
+contain	O
+the	O
+3	O
+.	O
+2	O
+kb	O
+EcoRllPvuIl	O
+fragment	O
+analogous	O
+to	O
+that	O
+present	O
+in	O
+pBRB7	O
+.	O
+2	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+pBCB2	O
+.	O
+
+13	O
+-	O
+2	O
+.	O
+18	O
+.	O
+
+To	O
+identify	O
+cl	O
+-	O
+repressible	O
+promoters	O
+,	O
+we	O
+introduced	O
+selected	O
+fragments	O
+
+7672	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+4	O
+f	O
+-	O
+-	O
++	O
+
+I	O
+4	O
+P1	O
+4	O
+-	O
+4	O
+-	O
+4	O
+
+ECAR	O
+H	O
+C	O
+B	O
+R	O
+P	O
+
+4	O
+4	O
+.	O
+4	O
+,	O
+~	O
+4	O
+,	O
+1	O
+1	O
+4	O
+.	O
+
+I	O
+4	O
+,	O
+I	O
+11	O
+
+t	O
+t	O
+t	O
+t	O
+t	O
+E	O
+G	O
+R	O
+N	O
+E	O
+B	O
+R	O
+P	O
+
+4	O
+4	O
+-	O
+
+4	O
+
+1	O
+'	O
+'	O
+110z	O
+I	O
+I	O
+I	O
+I	O
+I	O
+I	O
+1	O
+
+3	O
+.	O
+2	O
+1	O
+.	O
+5	O
+1	O
+.	O
+0	O
+0	O
+.	O
+5	O
+0	O
+
+P7	O
+
+pBRB7	O
+.	O
+2	O
+
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+cl1	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+-	O
+
+r	O
+~	O
+/	O
+>	O
+'	O
+pFAO2	O
+
+*	O
+-	O
+lacZ	O
+pBCB2	O
+.	O
+13	O
+
+<	O
+-	O
+lacZ	O
+Z	O
+pBCB2	O
+.	O
+16	O
+<	O
+-	O
+lacZX	O
+pBCB2	O
+.	O
+18	O
+
+Fig	O
+.	O
+
+1	O
+.	O
+
+The	O
+cl	O
+regions	O
+of	O
+P1	O
+and	O
+P7	O
+.	O
+
+A	O
+restriction	O
+map	O
+is	O
+indicated	O
+by	O
+the	O
+solid	O
+line	O
+in	O
+the	O
+upper	O
+part	O
+of	O
+the	O
+figure	O
+.	O
+
+Sites	O
+for	O
+EcoRI	O
+(	O
+E	O
+)	O
+,	O
+Pvul	O
+(	O
+P	O
+)	O
+,	O
+NnrI	O
+(	O
+N	O
+)	O
+,	O
+Bgll	O
+(	O
+G	O
+)	O
+,	O
+BamHI	O
+(	O
+B	O
+)	O
+,	O
+and	O
+EcoRV	O
+(	O
+R	O
+)	O
+are	O
+shown	O
+.	O
+
+The	O
+sequencing	O
+strategy	O
+is	O
+indicated	O
+by	O
+the	O
+horizontal	O
+arrows	O
+.	O
+
+Letters	O
+and	O
+arrows	O
+above	O
+and	O
+below	O
+the	O
+map	O
+refer	O
+to	O
+sites	O
+and	O
+sequence	O
+analysis	O
+for	O
+P1	O
+and	O
+P7	O
+,	O
+respectively	O
+.	O
+
+The	O
+size	O
+of	O
+this	O
+region	O
+(	O
+in	O
+kilobase	O
+pairs	O
+)	O
+is	O
+indicated	O
+below	O
+the	O
+map	O
+.	O
+
+The	O
+DNA	O
+fragments	O
+present	O
+in	O
+selected	O
+plasmids	O
+are	O
+illustrated	O
+by	O
+boxes	O
+at	O
+the	O
+bottom	O
+of	O
+the	O
+figure	O
+.	O
+
+The	O
+dashed	O
+line	O
+reveals	O
+the	O
+approximate	O
+position	O
+of	O
+the	O
+cl	O
+gene	O
+(	O
+2	O
+)	O
+.	O
+
+The	O
+sites	O
+of	O
+the	O
+-	O
+yb	O
+mutations	O
+introduced	O
+into	O
+pFA02	O
+are	O
+indicated	O
+by	O
+asterisks	O
+.	O
+
+pFA02	O
+.	O
+16	O
+and	O
+pFA02	O
+.	O
+26	O
+contain	O
+insertions	O
+located	O
+0	O
+.	O
+9	O
+kb	O
+and	O
+1	O
+.	O
+4	O
+kb	O
+,	O
+respectively	O
+,	O
+from	O
+the	O
+PvuIl	O
+site	O
+at	O
+the	O
+left	O
+side	O
+of	O
+the	O
+map	O
+.	O
+
+The	O
+direction	O
+of	O
+the	O
+lacZ	O
+open	O
+reading	O
+frame	O
+in	O
+pBCB2	O
+.	O
+13	O
+-	O
+18	O
+is	O
+indicated	O
+by	O
+the	O
+adjacent	O
+arrow	O
+.	O
+
+from	O
+the	O
+cI	O
+region	O
+of	O
+P1	O
+into	O
+pCB192	O
+,	O
+a	O
+promoter	O
+-	O
+probe	O
+vector	O
+containing	O
+promoterless	O
+copies	O
+of	O
+lacZ	O
+and	O
+galK	O
+extending	O
+in	O
+opposite	O
+directions	O
+from	O
+a	O
+multiple	O
+cloning	O
+site	O
+(	O
+21	O
+)	O
+.	O
+
+The	O
+source	O
+of	O
+P1	O
+DNA	O
+for	O
+these	O
+constructions	O
+was	O
+pZHA3	O
+,	O
+a	O
+derivative	O
+of	O
+pBRB7	O
+.	O
+2	O
+that	O
+contains	O
+a	O
+HindIlI	O
+linker	O
+at	O
+the	O
+single	O
+EcoRV	O
+site	O
+located	O
+about	O
+200	O
+bps	O
+upstream	O
+of	O
+the	O
+cl	O
+open	O
+reading	O
+frame	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+pBCB2	O
+.	O
+13	O
+contains	O
+a	O
+460	O
+bp	O
+fragment	O
+of	O
+P1	O
+DNA	O
+extending	O
+from	O
+the	O
+EcoRV	O
+site	O
+to	O
+a	O
+Bgll	O
+site	O
+within	O
+the	O
+cI	O
+open	O
+reading	O
+frame	O
+.	O
+
+pBCB2	O
+.	O
+
+16	O
+contains	O
+a	O
+130	O
+bp	O
+fragment	O
+extending	O
+from	O
+the	O
+EcoRV	O
+site	O
+to	O
+a	O
+BamHI	O
+site	O
+located	O
+about	O
+100	O
+bps	O
+upstream	O
+of	O
+the	O
+cl	O
+open	O
+reading	O
+frame	O
+,	O
+while	O
+pBCB2	O
+.	O
+18	O
+contains	O
+the	O
+region	O
+extending	O
+from	O
+this	O
+BamHI	O
+site	O
+to	O
+the	O
+Bglll	O
+site	O
+within	O
+the	O
+open	O
+reading	O
+frame	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+The	O
+orientation	O
+of	O
+the	O
+P1	O
+DNA	O
+fragments	O
+within	O
+these	O
+plasmids	O
+was	O
+confirmed	O
+by	O
+restriction	O
+mapping	O
+and	O
+DNA	O
+sequencing	O
+.	O
+
+To	O
+test	O
+for	O
+the	O
+regulation	O
+of	O
+promoter	O
+expression	O
+by	O
+cl	O
+,	O
+we	O
+transformed	O
+pBCB2	O
+.	O
+13	O
+and	O
+its	O
+derivatives	O
+into	O
+CB454	O
+(	O
+pBRB7	O
+.	O
+152	O
+)	O
+and	O
+CB454	O
+(	O
+pFAO2	O
+.	O
+152	O
+)	O
+,	O
+two	O
+strains	O
+that	O
+express	O
+P7cl	O
+and	O
+Pll	O
+,	O
+respectively	O
+,	O
+from	O
+the	O
+pCB192	O
+-	O
+compatible	O
+kanamycin	O
+-	O
+resistant	O
+vector	O
+pDPT152	O
+(	O
+22	O
+)	O
+.	O
+
+Cells	O
+harboring	O
+both	O
+plasmids	O
+were	O
+selected	O
+by	O
+their	O
+resistance	O
+to	O
+both	O
+ampicillin	O
+and	O
+kanamycin	O
+.	O
+
+lacZ	O
+expression	O
+was	O
+measured	O
+by	O
+the	O
+procedure	O
+of	O
+Miller	O
+(	O
+23	O
+)	O
+.	O
+
+pBRB7	O
+.	O
+152	O
+was	O
+generated	O
+by	O
+introducing	O
+PlEcoRI	O
+-	O
+7	O
+into	O
+pDPT152	O
+.	O
+
+pBRB7	O
+.	O
+152	O
+has	O
+sustained	O
+a	O
+spontaneous	O
+deletion	O
+within	O
+the	O
+EcoRI	O
+-	O
+7	O
+fragment	O
+that	O
+results	O
+in	O
+the	O
+loss	O
+of	O
+2	O
+.	O
+5	O
+kb	O
+of	O
+P1	O
+DNA	O
+from	O
+the	O
+far	O
+left	O
+side	O
+of	O
+the	O
+P1	O
+genetic	O
+map	O
+,	O
+but	O
+retains	O
+the	O
+3	O
+.	O
+2	O
+kb	O
+PvuHlEcoRI	O
+fragment	O
+required	O
+for	O
+cl	O
+expression	O
+that	O
+is	O
+present	O
+in	O
+pBRB7	O
+.	O
+2	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+7673	O
+
+z	O
+
+I	O
+011Z	O
+I	O
+
+e	O
+.	O
+,	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Table	O
+1	O
+.	O
+
+Complementation	O
+of	O
+PIci	O
+.	O
+245	O
+by	O
+plasmids	O
+that	O
+contain	O
+cI	O
+genes	O
+.	O
+
+Phenotype	O
+Efficiency	O
+Relative	O
+
+of	O
+of	O
+Efficiency	O
+of	O
+Plasmid	O
+cI	O
+gene	O
+Lysogeny	O
+Lysogeny	O
+pBR322	O
+1	O
+.	O
+5x	O
+10	O
+-	O
+6	O
+6	O
+.	O
+0x	O
+10	O
+-	O
+6	O
+pBRB7	O
+.	O
+2	O
+Plcl	O
++	O
+2	O
+.	O
+5	O
+x	O
+10	O
+-	O
+'	O
+1	O
+.	O
+0	O
+
+pBRB55	O
+.	O
+1	O
+Plcl	O
+-	O
+am	O
+1	O
+.	O
+4	O
+x	O
+10	O
+-	O
+6	O
+5	O
+.	O
+6	O
+x	O
+10	O
+-	O
+6	O
+pBRB169	O
+.	O
+1	O
+PlCl	O
+-	O
+am	O
+2	O
+.	O
+1	O
+x	O
+10	O
+-	O
+6	O
+8	O
+.	O
+4	O
+x	O
+10	O
+-	O
+6	O
+pFAO2	O
+P7cl	O
++	O
+8	O
+.	O
+7	O
+x	O
+10	O
+-	O
+2	O
+0	O
+.	O
+35	O
+
+pFAO2	O
+.	O
+16	O
+P7c	O
+I	O
+-	O
+,	O
+4	O
+.	O
+7	O
+x	O
+10	O
+-	O
+6	O
+1	O
+.	O
+9	O
+X	O
+10	O
+-	O
+5	O
+pFAO2	O
+.	O
+26	O
+P7cI	O
+-	O
+1	O
+3	O
+.	O
+1	O
+x	O
+10	O
+-	O
+6	O
+1	O
+.	O
+2	O
+x	O
+10	O
+-	O
+5	O
+
+Complementation	O
+for	O
+lysogeny	O
+was	O
+carried	O
+out	O
+as	O
+described	O
+by	O
+Devlin	O
+et	O
+al	O
+.	O
+
+(	O
+26	O
+)	O
+.	O
+
+The	O
+plasmids	O
+were	O
+carried	O
+by	O
+E	B
+.	I
+coli	I
+K336	O
+.	O
+
+Cells	O
+were	O
+grown	O
+to	O
+mid	O
+-	O
+log	O
+phase	O
+at	O
+370	O
+in	O
+LB	O
+containing	O
+50	O
+tig	O
+/	O
+m1	O
+sodium	O
+ampicillin	O
+and	O
+infected	O
+with	O
+Plcl	O
+.	O
+245	O
+at	O
+a	O
+multiplicity	O
+of	O
+infection	O
+of	O
+5	O
+in	O
+the	O
+presence	O
+of	O
+50	O
+mM	O
+CaC12	O
+.	O
+
+After	O
+10	O
+minutes	O
+,	O
+non	O
+-	O
+absorbed	O
+phage	O
+were	O
+removed	O
+by	O
+centrifugation	O
+and	O
+the	O
+infection	O
+was	O
+allowed	O
+to	O
+proceed	O
+for	O
+2	O
+hours	O
+at	O
+370	O
+.	O
+
+The	O
+infected	O
+cells	O
+were	O
+plated	O
+on	O
+LB	O
+plates	O
+containing	O
+50	O
+pLg	O
+/	O
+ml	O
+sodium	O
+ampicillin	O
+,	O
+50	O
+pLg	O
+/	O
+ml	O
+chloramphenicol	O
+,	O
+and	O
+40	O
+mM	O
+sodium	O
+citrate	O
+.	O
+
+The	O
+efficiency	O
+of	O
+lysogeny	O
+is	O
+defined	O
+as	O
+the	O
+number	O
+of	O
+ApRCmR	O
+cells	O
+at	O
+the	O
+end	O
+of	O
+infection	O
+divided	O
+by	O
+the	O
+number	O
+of	O
+ApR	O
+cells	O
+present	O
+at	O
+the	O
+start	O
+of	O
+the	O
+infection	O
+.	O
+
+To	O
+construct	O
+pFA02	O
+.	O
+152	O
+,	O
+we	O
+introduced	O
+a	O
+2	O
+.	O
+8	O
+kb	O
+EcoRV	O
+fragment	O
+of	O
+P7	O
+DNA	O
+containing	O
+the	O
+cl	O
+gene	O
+(	O
+Figure	O
+1	O
+)	O
+into	O
+the	O
+single	O
+EcoRI	O
+site	O
+of	O
+pDPT152	O
+after	O
+it	O
+had	O
+been	O
+rendered	O
+blunt	O
+-	O
+ended	O
+by	O
+extension	O
+with	O
+T4	O
+DNA	O
+polymerase	O
+.	O
+
+cl	O
+expression	O
+by	O
+cells	O
+harboring	O
+either	O
+pBRB7	O
+.	O
+152	O
+or	O
+pFA02	O
+.	O
+152	O
+was	O
+confirmed	O
+by	O
+measuring	O
+their	O
+ability	O
+to	O
+form	O
+chloramphenicol	O
+-	O
+resistant	O
+lysogens	O
+when	O
+infected	O
+with	O
+Plcl	O
+.	O
+245Cm	O
+.	O
+
+,	O
+yb	O
+insertional	O
+mutagenesis	O
+.	O
+
+Insertional	O
+mutagenesis	O
+of	O
+P7cl	O
+was	O
+carried	O
+out	O
+using	O
+the	O
+'	O
+yb	O
+transposon	O
+of	O
+F	O
+(	O
+24	O
+)	O
+as	O
+described	O
+by	O
+Devlin	O
+et	O
+al	O
+.	O
+
+(	O
+25	O
+)	O
+.	O
+
+E	B
+.	I
+coli	I
+W1485	O
+(	O
+pFA02	O
+)	O
+was	O
+mated	O
+with	O
+the	O
+F	O
+-	O
+strain	O
+MX648	O
+and	O
+subsequently	O
+plated	O
+on	O
+ampicillin	O
+(	O
+to	O
+select	O
+for	O
+the	O
+plasmid	O
+)	O
+and	O
+streptomycin	O
+sulfate	O
+(	O
+to	O
+select	O
+for	O
+the	O
+recipient	O
+strain	O
+)	O
+.	O
+
+Transconjugants	O
+which	O
+could	O
+support	O
+only	O
+lytic	O
+growth	O
+upon	O
+infection	O
+by	O
+P7cl	O
+.	O
+1	O
+(	O
+as	O
+scored	O
+by	O
+cross	O
+-	O
+streak	O
+analysis	O
+;	O
+18	O
+)	O
+were	O
+assumed	O
+to	O
+have	O
+lost	O
+cl	O
+-	O
+complementing	O
+activity	O
+and	O
+were	O
+characterized	O
+further	O
+.	O
+
+The	O
+positions	O
+of	O
+two	O
+cl	O
+-	O
+insertional	O
+mutations	O
+,	O
+carried	O
+by	O
+pFA02	O
+.	O
+16	O
+and	O
+pFA02	O
+.	O
+26	O
+,	O
+were	O
+identified	O
+by	O
+restriction	O
+mapping	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+DNA	O
+sequencing	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+was	O
+carried	O
+out	O
+using	O
+the	O
+M13	O
+-	O
+dideoxy	O
+technique	O
+of	O
+Sanger	O
+et	O
+al	O
+.	O
+
+(	O
+26	O
+)	O
+.	O
+
+Selected	O
+DNA	O
+fragments	O
+containing	O
+the	O
+cl	O
+wildtype	O
+or	O
+mutant	O
+genes	O
+were	O
+introduced	O
+into	O
+M13	O
+mp8	O
+or	O
+mp9	O
+.	O
+
+18	O
+-	O
+nucleotide	O
+oligomers	O
+complementary	O
+to	O
+defined	O
+sequences	O
+within	O
+the	O
+cl	O
+gene	O
+were	O
+extended	O
+using	O
+the	O
+Klenow	O
+fragment	O
+of	O
+DNA	O
+polymerase	O
+in	O
+the	O
+presence	O
+of	O
+dideoxynucleotide	O
+triphosphates	O
+and	O
+analyzed	O
+by	O
+polyacrylamide	O
+-	O
+urea	O
+gel	O
+electrophoresis	O
+.	O
+
+The	O
+sequencing	O
+strategy	O
+is	O
+shown	O
+in	O
+Figure	O
+1	O
+.	O
+
+RESULTS	O
+
+Localization	O
+of	O
+the	O
+P7cJ	O
+gene	O
+.	O
+
+Initial	O
+localization	O
+of	O
+the	O
+P7cl	O
+gene	O
+was	O
+undertaken	O
+by	O
+subjecting	O
+pFA02	O
+to	O
+'	O
+yb	O
+mutagenesis	O
+and	O
+determining	O
+the	O
+map	O
+position	O
+of	O
+inserts	O
+which	O
+destroy	O
+the	O
+ability	O
+of	O
+the	O
+plasmids	O
+to	O
+complement	O
+a	O
+P7cl	O
+-	O
+mutation	O
+(	O
+as	O
+determined	O
+by	O
+cross	O
+-	O
+streak	O
+analysis	O
+)	O
+.	O
+
+pFA02	O
+and	O
+the	O
+-	O
+yb	O
+insertion	O
+mutants	O
+were	O
+tested	O
+further	O
+by	O
+comparing	O
+their	O
+ability	O
+to	O
+complement	O
+a	O
+PIcI	O
+amber	O
+mutation	O
+with	O
+the	O
+complementation	O
+activity	O
+of	O
+plasmids	O
+containing	O
+cl	O
+genes	O
+isolated	O
+
+7674	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+B	O
+C	O
+D	O
+E	O
+F	O
+G	O
+
+*	O
+.	O
+4	O
+
+68	O
+
+43	O
+
+29	O
+-	O
+_	O
+-	O
+=	O
+I	O
+=	O
+Am	O
+~	O
+W	O
+_	O
+
+18	O
+
+14	O
+p	O
+
+Fig	O
+.	O
+
+2	O
+.	O
+
+In	O
+vitro	O
+transcription	O
+-	O
+translation	O
+of	O
+plasmids	O
+carrying	O
+the	O
+cl	O
+region	O
+of	O
+P1	O
+and	O
+P7	O
+.	O
+
+Proteins	O
+encoded	O
+by	O
+selected	O
+plasmids	O
+were	O
+labeled	O
+with	O
+35S	O
+methionine	O
+according	O
+to	O
+the	O
+procedure	O
+of	O
+DeVries	O
+and	O
+Zubay	O
+(	O
+27	O
+)	O
+,	O
+using	O
+a	O
+commercial	O
+in	O
+vitro	O
+transcription	O
+/	O
+tramnslation	O
+kit	O
+from	O
+Amersham	O
+Corporation	O
+.	O
+
+The	O
+reaction	O
+mixtures	O
+were	O
+subjected	O
+to	O
+electrophoresis	O
+on	O
+a	O
+12	O
+.	O
+5	O
+%	O
+SDS	O
+-	O
+polyacrylamide	O
+gel	O
+and	O
+the	O
+labeled	O
+proteins	O
+were	O
+visualized	O
+by	O
+autoradiography	O
+.	O
+
+The	O
+migration	O
+of	O
+14C	O
+-	O
+labeled	O
+protein	O
+molecular	O
+weight	O
+standards	O
+(	O
+Bethesda	O
+Research	O
+Laboratories	O
+)	O
+is	O
+indicated	O
+at	O
+the	O
+left	O
+side	O
+of	O
+the	O
+figure	O
+.	O
+
+Plasmids	O
+present	O
+in	O
+each	O
+lane	O
+are	O
+:	O
+A	O
+.	O
+
+pBRB55	O
+.	O
+1	O
+;	O
+B	O
+.	O
+
+pBRB169	O
+.	O
+1	O
+;	O
+C	O
+.	O
+
+pBRB7	O
+.	O
+2	O
+;	O
+D	O
+.	O
+
+pFAO2	O
+;	O
+E	O
+.	O
+
+pFAO2	O
+.	O
+16	O
+;	O
+F	O
+.	O
+
+pFAO2	O
+.	O
+26	O
+;	O
+G	O
+.	O
+
+pBR322	O
+.	O
+
+from	O
+P1	O
+wildtype	O
+and	O
+amber	O
+mutants	O
+.	O
+
+Lysogeny	O
+by	O
+cells	O
+infected	O
+with	O
+Plcl	O
+.	O
+245Cm	O
+was	O
+scored	O
+as	O
+the	O
+growth	O
+of	O
+infected	O
+cells	O
+on	O
+ampicillin	O
+(	O
+to	O
+select	O
+for	O
+the	O
+resident	O
+plasmid	O
+)	O
+and	O
+chloramphenicol	O
+(	O
+to	O
+select	O
+for	O
+the	O
+phage	O
+genome	O
+)	O
+.	O
+
+The	O
+values	O
+observed	O
+for	O
+the	O
+two	O
+plasmids	O
+containing	O
+Plcl	O
+and	O
+P7cl	O
+(	O
+pBRB7	O
+.	O
+2	O
+and	O
+pFA02	O
+,	O
+respectively	O
+)	O
+are	O
+very	O
+similar	O
+and	O
+significantly	O
+higher	O
+than	O
+those	O
+obtained	O
+for	O
+pBR322	O
+or	O
+for	O
+any	O
+of	O
+the	O
+plasmids	O
+carrying	O
+
+Table	O
+2	O
+.	O
+
+Assay	O
+for	O
+lacZ	O
+expression	O
+from	O
+plasmids	O
+containing	O
+P1	O
+DNA	O
+fragments	O
+.	O
+
+,	O
+3	O
+-	O
+galactosidase	O
+activity	O
+(	O
+units	O
+)	O
+
+minus	O
+cI	O
+plus	O
+Pici	O
+plus	O
+P7cl	O
+relative	O
+activity	O
+
+(	O
+pDPT152	O
+)	O
+(	O
+pBB7	O
+.	O
+152	O
+)	O
+(	O
+pFA02	O
+.	O
+152	O
+)	O
++	O
+PICJ	O
++	O
+P7cJ	O
+
+pCB192	O
+0	O
+.	O
+58	O
+0	O
+.	O
+55	O
+0	O
+.	O
+54	O
+0	O
+.	O
+95	O
+0	O
+.	O
+93	O
+pBCB2	O
+.	O
+13	O
+154	O
+15	O
+.	O
+2	O
+13	O
+.	O
+6	O
+0	O
+.	O
+10	O
+0	O
+.	O
+09	O
+pBCB2	O
+.	O
+16	O
+1	O
+.	O
+1	O
+1	O
+.	O
+2	O
+1	O
+.	O
+1	O
+1	O
+.	O
+1	O
+1	O
+.	O
+0	O
+pBCB2	O
+.	O
+18	O
+4	O
+.	O
+0	O
+3	O
+.	O
+4	O
+3	O
+.	O
+9	O
+0	O
+.	O
+9	O
+1	O
+.	O
+0	O
+
+Cells	O
+containing	O
+derivatives	O
+of	O
+the	O
+ApR	O
+promoter	O
+-	O
+probe	O
+plasmid	O
+pCB192	O
+and	O
+the	O
+compatible	O
+KnR	O
+plasmid	O
+pDPT152	O
+were	O
+grown	O
+in	O
+LB	O
+at	O
+37	O
+?	O
+.	O
+
+When	O
+they	O
+reached	O
+mid	O
+-	O
+log	O
+phase	O
+,	O
+the	O
+cells	O
+were	O
+chilled	O
+,	O
+lysed	O
+,	O
+and	O
+assayed	O
+for	O
+(	O
+3	O
+-	O
+galactosidase	O
+activity	O
+according	O
+to	O
+the	O
+procedure	O
+of	O
+Miller	O
+(	O
+23	O
+)	O
+.	O
+
+Plasmids	O
+derived	O
+from	O
+pCB192	O
+are	O
+indicated	O
+at	O
+the	O
+left	O
+side	O
+of	O
+the	O
+Table	O
+.	O
+
+Plasmids	O
+derived	O
+from	O
+pDPT152	O
+are	O
+indicated	O
+in	O
+parentheses	O
+across	O
+the	O
+top	O
+of	O
+the	O
+Table	O
+.	O
+
+The	O
+values	O
+reported	O
+are	O
+the	O
+average	O
+of	O
+two	O
+independent	O
+experiments	O
+.	O
+
+Relative	O
+activity	O
+is	O
+defined	O
+as	O
+the	O
+f3	O
+-	O
+galactosidase	O
+activity	O
+measured	O
+in	O
+cells	O
+harboring	O
+plasmids	O
+expressing	O
+cl	O
+divided	O
+by	O
+the	O
+activity	O
+measured	O
+in	O
+cells	O
+carrying	O
+only	O
+pDPT152	O
+.	O
+
+7675	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+GATATCCAATCAGGAGTACC	O
+GCATCACCCAAGACGACCTG	O
+GATGATCTCACTGACACAAT	O
+CGAATATCTCATGGCCACTA	O
+ACCAGCCAGACTCACAATAA	O
+105	O
+v	O
+-	O
+-	O
+
+TtgAca	O
+TATAATG	O
+
+CTAATAAATCTATTATTTTC	O
+GTTGGATCCTTCTATAATGG	O
+TGGCCAACAACTCCCAGTGT	O
+AATCCGCTGTGAGTTGTTGG	O
+CCATGTCAATTCTGGAGGAG	O
+210	O
+
+b	O
+-	O
+-	O
+-	O
+-	O
+-	O
+I	O
+I	O
+GGAGGtG	O
+
+ATG	O
+ATA	O
+AAT	O
+TAT	O
+GTC	O
+TAC	O
+GGC	O
+GAA	O
+CAA	O
+CTG	O
+TAC	O
+CAG	O
+GAG	O
+TTC	O
+GTC	O
+AGC	O
+TTC	O
+AGG	O
+GAT	O
+CTC	O
+TTT	O
+CTA	O
+AAA	O
+AAA	O
+GCT	O
+GTT	O
+GCA	O
+CGC	O
+GCC	O
+CAA	O
+300	O
+MET	O
+lIe	O
+Asn	O
+Tyr	O
+Vat	O
+Tyr	O
+Gly	O
+Glu	O
+Gin	O
+Leu	O
+Tyr	O
+Gin	O
+Gtu	O
+Phe	O
+Vat	O
+Ser	O
+Phe	O
+Arg	O
+Asp	O
+Leu	O
+Phe	O
+Leu	O
+Lys	O
+Lys	O
+Ala	O
+Val	O
+Ala	O
+Arg	O
+Ala	O
+Gtn	O
+
+tag	O
+(	O
+cl	O
+.	O
+55	O
+)	O
+
+CAC	O
+GTT	O
+GAT	O
+GCC	O
+GCC	O
+AGC	O
+GAC	O
+GGT	O
+CGT	O
+CCT	O
+GTT	O
+CGC	O
+CCG	O
+GTT	O
+GTC	O
+GTT	O
+CTG	O
+CCG	O
+TTC	O
+AM	O
+GM	O
+ACG	O
+GAC	O
+AGC	O
+ATT	O
+CAG	O
+GCT	O
+GMA	O
+ATT	O
+GAT	O
+390	O
+His	O
+Val	O
+Asp	O
+Ala	O
+Ala	O
+Ser	O
+Asp	O
+Gly	O
+Arg	O
+Pro	O
+Vat	O
+Arg	O
+Pro	O
+Vat	O
+Vat	O
+Vat	O
+Leu	O
+Pro	O
+Phe	O
+Lys	O
+Glu	O
+Thr	O
+Asp	O
+Ser	O
+lIe	O
+Gin	O
+Ala	O
+Glu	O
+lie	O
+Asp	O
+
+T	O
+A	O
+C	O
+A	O
+G	O
+
+AAA	O
+TGG	O
+ACA	O
+TTA	O
+ATG	O
+GCG	O
+CGG	O
+GAA	O
+CTG	O
+GAG	O
+CAG	O
+TAC	O
+CCA	O
+GAT	O
+CTC	O
+MT	O
+ATC	O
+CCA	O
+MG	O
+ACT	O
+ATT	O
+TTA	O
+TAT	O
+CCT	O
+GTA	O
+CCT	O
+AAC	O
+ATC	O
+CTT	O
+CGC	O
+480	O
+
+9	O
+
+Lys	O
+Trp	O
+Thr	O
+Leu	O
+MET	O
+Ala	O
+Arg	O
+Glu	O
+Leu	O
+Gtu	O
+Gin	O
+Tyr	O
+Pro	O
+Asp	O
+Leu	O
+Asn	O
+lIe	O
+Pro	O
+Lys	O
+Thr	O
+lie	O
+Leu	O
+Tyr	O
+Pro	O
+Vat	O
+Pro	O
+Asn	O
+lIe	O
+Leu	O
+Arg	O
+
+A	O
+T	O
+C	O
+
+GGT	O
+GTG	O
+CGT	O
+AAG	O
+GTT	O
+ACG	O
+ACT	O
+TAT	O
+CAG	O
+ACA	O
+GAA	O
+GCA	O
+GTG	O
+MC	O
+AGC	O
+GTC	O
+AAT	O
+ATG	O
+ACC	O
+GCT	O
+GGC	O
+CGC	O
+ATT	O
+ATT	O
+CAT	O
+CTG	O
+ATT	O
+GAT	O
+AAG	O
+GAC	O
+570	O
+Gly	O
+Vat	O
+Arg	O
+Lys	O
+Vat	O
+Thr	O
+Thr	O
+Tyr	O
+Gin	O
+Thr	O
+Glu	O
+Ala	O
+Vat	O
+Asn	O
+Ser	O
+Vat	O
+Asn	O
+MET	O
+Thr	O
+Ala	O
+Gly	O
+Arg	O
+lIe	O
+lIe	O
+His	O
+Leu	O
+lIe	O
+Asp	O
+Lys	O
+Asp	O
+
+G	O
+
+ATT	O
+CGC	O
+ATC	O
+CAA	O
+AM	O
+AGC	O
+GCG	O
+GGG	O
+ATC	O
+MT	O
+GAG	O
+CAC	O
+AGT	O
+GCG	O
+AAA	O
+TAC	O
+ATA	O
+GAG	O
+MC	O
+CTG	O
+GAA	O
+GCA	O
+ACA	O
+AM	O
+GAG	O
+CTA	O
+ATG	O
+AAG	O
+CAG	O
+TAC	O
+660	O
+lle	O
+Arg	O
+lIe	O
+Gin	O
+Lys	O
+Ser	O
+Ala	O
+Gly	O
+lIe	O
+Asn	O
+Gtu	O
+His	O
+Ser	O
+Ala	O
+Lys	O
+Tyr	O
+lIe	O
+Gtu	O
+Asn	O
+Leu	O
+Gtu	O
+Ala	O
+Thr	O
+Lys	O
+Gtu	O
+Leu	O
+MET	O
+Lys	O
+Gin	O
+Tyr	O
+
+T	O
+T	O
+
+CCG	O
+GAG	O
+GAT	O
+GAA	O
+AAA	O
+TTC	O
+CGT	O
+ATG	O
+CGC	O
+GTA	O
+CAC	O
+GGC	O
+TTT	O
+AGC	O
+GAA	O
+ACA	O
+ATG	O
+CTG	O
+CGC	O
+GTC	O
+CAT	O
+TAC	O
+ATT	O
+TCC	O
+AGT	O
+AGC	O
+CCT	O
+AAC	O
+TAC	O
+AAT	O
+750	O
+Pro	O
+Glu	O
+Asp	O
+Glu	O
+Lys	O
+Phe	O
+Arg	O
+MET	O
+Arg	O
+Vat	O
+His	O
+Gly	O
+Phe	O
+Ser	O
+Gtu	O
+Thr	O
+MET	O
+Leu	O
+Arg	O
+Vat	O
+His	O
+Tyr	O
+lie	O
+Ser	O
+Ser	O
+Ser	O
+Pro	O
+Asn	O
+Tyr	O
+Asn	O
+
+Phe	O
+
+T	O
+C	O
+G	O
+T	O
+T	O
+
+I	O
+~	O
+~	O
+~	O
+I	O
+I	O
+II	O
+
+GAT	O
+GGC	O
+MA	O
+TCA	O
+GTT	O
+AGT	O
+TAC	O
+CAT	O
+GTG	O
+CTG	O
+CTA	O
+TGT	O
+GGC	O
+GTG	O
+TTT	O
+ATC	O
+TGC	O
+GAT	O
+GM	O
+ACT	O
+CTC	O
+CGA	O
+GAT	O
+GGA	O
+ATC	O
+ATC	O
+ATC	O
+AAC	O
+GGT	O
+GAA	O
+840	O
+
+e	O
+.	O
+.	O
+
+Asp	O
+Gly	O
+Lys	O
+Ser	O
+Vat	O
+Ser	O
+Tyr	O
+His	O
+Vat	O
+Leu	O
+Leu	O
+Cys	O
+Gly	O
+Vat	O
+Phe	O
+lie	O
+Cys	O
+Asp	O
+Glu	O
+Thr	O
+Leu	O
+Arg	O
+Asp	O
+Gly	O
+lIe	O
+lie	O
+lIe	O
+Asn	O
+Gly	O
+Gtu	O
+
+Pro	O
+
+C	O
+tag	O
+(	O
+cl	O
+.	O
+169	O
+)	O
+
+TTT	O
+GAG	O
+AM	O
+GCA	O
+AAA	O
+TTT	O
+AGC	O
+CTT	O
+TAT	O
+GAC	O
+TCT	O
+ATA	O
+GM	O
+CCG	O
+ATC	O
+ATC	O
+TGC	O
+GAC	O
+CGC	O
+TGG	O
+CCG	O
+CAG	O
+GCA	O
+AM	O
+ATA	O
+TAT	O
+CGC	O
+CTG	O
+GCA	O
+GAT	O
+930	O
+Phe	O
+Gtu	O
+Lys	O
+Ala	O
+Lys	O
+Phe	O
+Ser	O
+Leu	O
+Tyr	O
+Asp	O
+Ser	O
+lIe	O
+Glu	O
+Pro	O
+lie	O
+lie	O
+Cys	O
+Asp	O
+Arg	O
+Trp	O
+Pro	O
+Gin	O
+Ala	O
+Lys	O
+lIe	O
+Tyr	O
+Arg	O
+Leu	O
+Ala	O
+Asp	O
+
+T	O
+
+ATT	O
+GM	O
+MT	O
+GTA	O
+AM	O
+AM	O
+CM	O
+ATT	O
+GCC	O
+ATC	O
+ACT	O
+CGC	O
+GM	O
+GAG	O
+AAA	O
+G	O
+GTC	O
+AM	O
+TCA	O
+GCC	O
+GCA	O
+TCA	O
+GTT	O
+ACG	O
+CGC	O
+AGC	O
+CGC	O
+AAA	O
+ACT	O
+AAG	O
+1020	O
+
+n	O
+-	O
+-	O
+-	O
+-	O
+-	O
+
+lie	O
+Glu	O
+Asn	O
+Vat	O
+Lys	O
+Lys	O
+Gin	O
+lIe	O
+Ala	O
+lie	O
+Thr	O
+Arg	O
+Glu	O
+Glu	O
+Lys	O
+Lys	O
+Vat	O
+Lys	O
+Ser	O
+Ala	O
+Ala	O
+Ser	O
+Vat	O
+Thr	O
+Arg	O
+Ser	O
+Arg	O
+Lys	O
+Thr	O
+Lys	O
+
+AAG	O
+GGG	O
+CAG	O
+CCA	O
+GTA	O
+AAC	O
+GAC	O
+MC	O
+CCC	O
+GAA	O
+AGC	O
+GCG	O
+CM	O
+TAG	O
+Lys	O
+Gly	O
+Gin	O
+Pro	O
+Val	O
+Asn	O
+Asp	O
+Asn	O
+Pro	O
+Glu	O
+Ser	O
+Ala	O
+Gin	O
+ter	O
+
+Fig	O
+.	O
+
+3	O
+.	O
+
+DNA	O
+sequence	O
+of	O
+PIcI	O
+and	O
+P7cl	O
+.	O
+
+The	O
+DNA	O
+sequence	O
+of	O
+PIcI	O
+is	O
+indicated	O
+.	O
+
+Positions	O
+where	O
+the	O
+sequence	O
+of	O
+P7cl	O
+differs	O
+from	O
+that	O
+of	O
+Plcl	O
+are	O
+indicated	O
+above	O
+the	O
+P1	O
+sequence	O
+.	O
+
+The	O
+amino	O
+acid	O
+sequence	O
+predicted	O
+by	O
+the	O
+open	O
+reading	O
+frame	O
+is	O
+given	O
+below	O
+the	O
+sequence	O
+.	O
+
+The	O
+two	O
+amino	O
+acid	O
+substitutions	O
+present	O
+in	O
+P7cl	O
+are	O
+shown	O
+below	O
+the	O
+open	O
+reading	O
+frame	O
+.	O
+
+The	O
+locations	O
+of	O
+the	O
+amber	O
+mutant	O
+codons	O
+in	O
+cl	O
+.	O
+55	O
+and	O
+ci	O
+.	O
+
+169	O
+are	O
+indicated	O
+by	O
+small	O
+letters	O
+above	O
+the	O
+sequence	O
+.	O
+
+Sites	O
+for	O
+selected	O
+restriction	O
+enzymes	O
+(	O
+EcoRV	O
+[	O
+v	O
+]	O
+;	O
+BamHI	O
+[	O
+b	O
+]	O
+;	O
+Bgll	O
+[	O
+g	O
+]	O
+;	O
+EcoRP	O
+[	O
+e	O
+]	O
+;	O
+and	O
+NruI	O
+[	O
+n	O
+]	O
+)	O
+are	O
+illustrated	O
+by	O
+dashed	O
+lines	O
+beneath	O
+the	O
+sequence	O
+.	O
+
+The	O
+cl	O
+repressor	O
+binding	O
+site	O
+is	O
+underlined	O
+.	O
+
+Inverted	O
+arrows	O
+beneath	O
+the	O
+sequence	O
+illustrate	O
+the	O
+inverted	O
+repeat	O
+sequence	O
+upstream	O
+of	O
+the	O
+open	O
+reading	O
+frame	O
+.	O
+
+Predicted	O
+promoter	O
+ribosome	O
+binding	O
+sites	O
+are	O
+indicated	O
+by	O
+the	O
+presence	O
+of	O
+the	O
+consensus	O
+sequences	O
+above	O
+and	O
+below	O
+the	O
+line	O
+,	O
+respectively	O
+.	O
+
+The	O
+DNA	O
+sequences	O
+of	O
+Plcl	O
+from	O
+bp	O
+1	O
+-	O
+134	O
+and	O
+bp	O
+1	O
+-	O
+434	O
+were	O
+reported	O
+previously	O
+(	O
+2	O
+,	O
+5	O
+)	O
+.	O
+
+mutant	O
+cl	O
+genes	O
+from	O
+either	O
+P1	O
+or	O
+P7	O
+(	O
+Table	O
+1	O
+)	O
+.	O
+
+The	O
+efficiency	O
+with	O
+which	O
+a	O
+cloned	O
+P7cl	O
+gene	O
+complements	O
+a	O
+PlcI	O
+mutation	O
+confirms	O
+previous	O
+genetic	O
+studies	O
+indicating	O
+that	O
+these	O
+two	O
+genes	O
+are	O
+functionally	O
+interchangeable	O
+(	O
+9	O
+)	O
+.	O
+
+The	O
+location	O
+of	O
+the	O
+'	O
+y6	O
+mutations	O
+that	O
+destroy	O
+cl	O
+-	O
+complementing	O
+activity	O
+suggests	O
+that	O
+the	O
+P7cl	O
+open	O
+reading	O
+frame	O
+occupies	O
+a	O
+map	O
+position	O
+similar	O
+to	O
+that	O
+of	O
+the	O
+P1	O
+open	O
+reading	O
+frame	O
+(	O
+Figure	O
+1	O
+)	O
+.	O
+
+7676	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Proteins	O
+produced	O
+by	O
+fragments	O
+containing	O
+Plcl	O
+.	O
+
+As	O
+an	O
+initial	O
+step	O
+in	O
+the	O
+comparison	O
+of	O
+the	O
+P1	O
+and	O
+P7	O
+repressors	O
+,	O
+we	O
+analyzed	O
+the	O
+gene	O
+products	O
+expressed	O
+from	O
+the	O
+cloned	O
+cl	O
+regions	O
+.	O
+
+In	O
+an	O
+in	O
+vitro	O
+transcription	O
+-	O
+translation	O
+reaction	O
+,	O
+plasmids	O
+coding	O
+for	O
+the	O
+wildtpe	O
+alleles	O
+of	O
+either	O
+PIcI	O
+or	O
+P7cl	O
+direct	O
+the	O
+production	O
+of	O
+a	O
+protein	O
+with	O
+an	O
+estimated	O
+molecular	O
+weight	O
+of	O
+33	O
+,	O
+000	O
+daltons	O
+(	O
+Figure	O
+2	O
+,	O
+Lanes	O
+C	O
+and	O
+D	O
+)	O
+,	O
+a	O
+size	O
+that	O
+agrees	O
+closely	O
+with	O
+the	O
+predicted	O
+molecular	O
+weight	O
+of	O
+the	O
+PIcI	O
+repressor	O
+reported	O
+previously	O
+(	O
+3	O
+,	O
+28	O
+)	O
+.	O
+
+The	O
+loss	O
+of	O
+the	O
+33	O
+,	O
+000	O
+dalton	O
+protein	O
+in	O
+the	O
+cl	O
+-	O
+'	O
+ya	O
+-	O
+induced	O
+P7	O
+mutant	O
+plasmids	O
+(	O
+Figure	O
+2	O
+,	O
+Lanes	O
+E	O
+and	O
+F	O
+)	O
+is	O
+consistent	O
+with	O
+its	O
+designation	O
+as	O
+the	O
+P7cl	O
+repressor	O
+.	O
+
+As	O
+expected	O
+,	O
+the	O
+33	O
+,	O
+000	O
+dalton	O
+protein	O
+is	O
+not	O
+observed	O
+when	O
+reaction	O
+mixtures	O
+contain	O
+DNA	O
+from	O
+Plcl	O
+amber	O
+mutants	O
+(	O
+Figure	O
+2	O
+,	O
+Lanes	O
+A	O
+and	O
+B	O
+)	O
+.	O
+
+DNA	O
+sequence	O
+analysis	O
+of	O
+the	O
+cl	O
+genes	O
+.	O
+
+To	O
+make	O
+a	O
+direct	O
+comparison	O
+between	O
+the	O
+Plcl	O
+and	O
+P7cl	O
+DNA	O
+sequences	O
+and	O
+to	O
+predict	O
+the	O
+amino	O
+acid	O
+sequences	O
+of	O
+the	O
+repressor	O
+proteins	O
+,	O
+we	O
+carried	O
+out	O
+M	O
+13	O
+-	O
+dideoxy	O
+sequence	O
+analysis	O
+of	O
+cloned	O
+fragments	O
+carrying	O
+the	O
+cl	O
+genes	O
+.	O
+
+The	O
+sequences	O
+of	O
+about	O
+1	O
+kb	O
+of	O
+P1	O
+and	O
+P7	O
+DNA	O
+were	O
+determined	O
+starting	O
+from	O
+a	O
+common	O
+EcoRV	O
+site	O
+predicted	O
+to	O
+lie	O
+approximately	O
+200	O
+bps	O
+upstream	O
+of	O
+the	O
+cl	O
+genes	O
+.	O
+
+The	O
+P1	O
+and	O
+P7	O
+sequences	O
+(	O
+Figure	O
+3	O
+)	O
+both	O
+contain	O
+an	O
+ATG	O
+initiation	O
+codon	O
+preceded	O
+by	O
+a	O
+putative	O
+ribosome	O
+binding	O
+sequence	O
+(	O
+29	O
+)	O
+situated	O
+211	O
+bps	O
+downstream	O
+of	O
+the	O
+EcoRV	O
+site	O
+.	O
+
+In	O
+each	O
+case	O
+,	O
+the	O
+initiation	O
+codon	O
+is	O
+followed	O
+by	O
+an	O
+open	O
+reading	O
+reading	O
+frame	O
+extending	O
+for	O
+283	O
+codons	O
+.	O
+
+The	O
+P1	O
+and	O
+P7	O
+open	O
+reading	O
+frames	O
+code	O
+for	O
+proteins	O
+with	O
+predicted	O
+molecular	O
+weights	O
+(	O
+32	O
+,	O
+515	O
+and	O
+32	O
+,	O
+499	O
+daltons	O
+,	O
+respectively	O
+)	O
+that	O
+agree	O
+closely	O
+with	O
+the	O
+values	O
+of	O
+the	O
+proteins	O
+expressed	O
+from	O
+the	O
+cloned	O
+DNA	O
+fragments	O
+(	O
+Figure	O
+2	O
+)	O
+and	O
+with	O
+results	O
+predicted	O
+independently	O
+for	O
+the	O
+purified	O
+PIcI	O
+repressor	O
+(	O
+3	O
+-	O
+4	O
+)	O
+.	O
+
+The	O
+localization	O
+of	O
+two	O
+PIcI	O
+amber	O
+mutations	O
+to	O
+the	O
+P1	O
+open	O
+reading	O
+frame	O
+confirms	O
+its	O
+identification	O
+as	O
+the	O
+cI	O
+coding	O
+sequence	O
+.	O
+
+cI	O
+.	O
+
+169	O
+contains	O
+an	O
+amber	O
+mutation	O
+that	O
+would	O
+result	O
+in	O
+a	O
+protein	O
+fragment	O
+of	O
+26	O
+,	O
+680	O
+daltons	O
+,	O
+a	O
+value	O
+that	O
+agrees	O
+well	O
+with	O
+the	O
+size	O
+of	O
+a	O
+protein	O
+fragment	O
+observed	O
+under	O
+the	O
+in	O
+vitro	O
+transcription	O
+/	O
+translation	O
+reaction	O
+conditions	O
+(	O
+Figure	O
+2	O
+,	O
+Lane	O
+B	O
+)	O
+.	O
+
+The	O
+cl	O
+.	O
+55	O
+amber	O
+mutation	O
+lies	O
+close	O
+to	O
+the	O
+N	O
+-	O
+terminal	O
+region	O
+of	O
+the	O
+protein	O
+,	O
+resulting	O
+in	O
+the	O
+production	O
+of	O
+a	O
+fragment	O
+of	O
+55	O
+amino	O
+acids	O
+that	O
+is	O
+apparently	O
+too	O
+small	O
+to	O
+resolve	O
+under	O
+the	O
+electrophoretic	O
+conditions	O
+used	O
+for	O
+separation	O
+of	O
+the	O
+proteins	O
+.	O
+
+Over	O
+60	O
+%	O
+of	O
+the	O
+amino	O
+acid	O
+sequence	O
+predicted	O
+for	O
+the	O
+PIcI	O
+open	O
+reading	O
+frame	O
+has	O
+been	O
+verified	O
+by	O
+amino	O
+acid	O
+sequence	O
+analysis	O
+of	O
+peptide	O
+fragments	O
+isolated	O
+from	O
+the	O
+purified	O
+repressor	O
+protein	O
+(	O
+see	O
+accompanying	O
+paper	O
+,	O
+reference	O
+3	O
+)	O
+.	O
+
+The	O
+DNA	O
+sequences	O
+of	O
+P1	O
+and	O
+P7	O
+are	O
+identical	O
+for	O
+a	O
+399	O
+-	O
+bp	O
+region	O
+that	O
+extends	O
+from	O
+the	O
+EcoRV	O
+site	O
+at	O
+the	O
+5	O
+'	O
+side	O
+of	O
+the	O
+cl	O
+gene	O
+to	O
+a	O
+point	O
+188	O
+bps	O
+within	O
+the	O
+open	O
+reading	O
+frame	O
+.	O
+
+The	O
+sequences	O
+within	O
+the	O
+Plcl	O
+and	O
+the	O
+P7cl	O
+open	O
+reading	O
+frames	O
+differ	O
+at	O
+only	O
+18	O
+positions	O
+,	O
+all	O
+but	O
+two	O
+of	O
+which	O
+occur	O
+in	O
+the	O
+wobble	O
+position	O
+of	O
+the	O
+predicted	O
+codon	O
+.	O
+
+From	O
+these	O
+results	O
+,	O
+we	O
+conclude	O
+that	O
+the	O
+functional	O
+identity	O
+of	O
+the	O
+P1	O
+and	O
+P7	O
+cl	O
+genes	O
+is	O
+a	O
+consequence	O
+of	O
+their	O
+nearly	O
+identical	O
+amino	O
+acid	O
+sequence	O
+.	O
+
+Analysis	O
+of	O
+promoters	O
+upstream	O
+of	O
+the	O
+cl	O
+open	O
+reading	O
+frame	O
+.	O
+
+Expression	O
+of	O
+Plcl	O
+was	O
+shown	O
+previously	O
+to	O
+require	O
+sequences	O
+on	O
+the	O
+distal	O
+side	O
+of	O
+a	O
+BamHI	O
+site	O
+(	O
+2	O
+,	O
+5	O
+)	O
+located	O
+about	O
+100	O
+bps	O
+upstream	O
+of	O
+the	O
+open	O
+reading	O
+frame	O
+(	O
+Figure	O
+3	O
+)	O
+.	O
+
+A	O
+binding	O
+site	O
+for	O
+the	O
+cl	O
+repressor	O
+has	O
+also	O
+been	O
+shown	O
+to	O
+exist	O
+close	O
+to	O
+this	O
+BamHI	O
+site	O
+(	O
+2	O
+,	O
+5	O
+,	O
+6	O
+)	O
+.	O
+
+To	O
+determine	O
+whether	O
+this	O
+region	O
+contains	O
+a	O
+promoter	O
+that	O
+is	O
+detectable	O
+in	O
+vivo	O
+and	O
+,	O
+further	O
+,	O
+to	O
+determine	O
+whether	O
+this	O
+promoter	O
+can	O
+be	O
+regulated	O
+by	O
+cl	O
+repressor	O
+proteins	O
+from	O
+either	O
+P1	O
+or	O
+P7	O
+,	O
+we	O
+introduced	O
+several	O
+DNA	O
+fragments	O
+from	O
+this	O
+region	O
+into	O
+the	O
+promoter	O
+probe	O
+vector	O
+pCB192	O
+,	O
+screened	O
+for	O
+promoter	O
+activity	O
+(	O
+as	O
+monitored	O
+by	O
+lacZ	O
+expression	O
+)	O
+and	O
+checked	O
+for	O
+repression	O
+of	O
+this	O
+activity	O
+in	O
+the	O
+presence	O
+of	O
+a	O
+compatible	O
+
+7677	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+plasmid	O
+expressing	O
+Plcl	O
+or	O
+P7cl	O
+.	O
+
+Cells	O
+harboring	O
+pBCB2	O
+.	O
+13	O
+(	O
+a	O
+plasmid	O
+which	O
+carries	O
+a	O
+460	O
+bp	O
+fragment	O
+of	O
+P1	O
+DNA	O
+that	O
+extends	O
+across	O
+the	O
+BamHI	O
+site	O
+upstream	O
+of	O
+cl	O
+into	O
+the	O
+open	O
+reading	O
+frame	O
+)	O
+are	O
+dark	O
+blue	O
+in	O
+the	O
+presence	O
+of	O
+Xgal	O
+and	O
+produce	O
+significant	O
+levels	O
+of	O
+3	O
+-	O
+galactosidase	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+In	O
+contrast	O
+,	O
+pBCB2	O
+.	O
+16	O
+and	O
+pBCB2	O
+.	O
+18	O
+(	O
+which	O
+each	O
+contain	O
+DNA	O
+from	O
+only	O
+one	O
+side	O
+of	O
+the	O
+BamHI	O
+site	O
+located	O
+in	O
+pBCB2	O
+.	O
+13	O
+)	O
+do	O
+not	O
+confer	O
+a	O
+blue	O
+color	O
+on	O
+their	O
+host	O
+cell	O
+in	O
+the	O
+presence	O
+of	O
+X	O
+-	O
+Gal	O
+and	O
+express	O
+negligible	O
+amounts	O
+of	O
+3	O
+-	O
+galactosidase	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+These	O
+observations	O
+suggest	O
+that	O
+expression	O
+from	O
+the	O
+promoter	O
+identified	O
+here	O
+requires	O
+sequences	O
+that	O
+span	O
+the	O
+BamHI	O
+site	O
+upstream	O
+of	O
+cl	O
+.	O
+
+Expression	O
+of	O
+cl	O
+from	O
+a	O
+compatible	O
+plasmid	O
+in	O
+the	O
+presence	O
+of	O
+pBCB2	O
+.	O
+
+13	O
+results	O
+in	O
+a	O
+90	O
+%	O
+reduction	O
+in	O
+promoter	O
+strength	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+This	O
+reduction	O
+is	O
+seen	O
+in	O
+the	O
+presence	O
+of	O
+either	O
+Plcl	O
+or	O
+P7cl	O
+,	O
+indicating	O
+that	O
+the	O
+two	O
+repressor	O
+proteins	O
+are	O
+both	O
+capable	O
+of	O
+repressing	O
+expression	O
+from	O
+this	O
+promoter	O
+.	O
+
+DISCUSSION	O
+.	O
+
+The	O
+DNA	O
+sequences	O
+of	O
+Plcl	O
+and	O
+P7cl	O
+differ	O
+at	O
+only	O
+18	O
+sites	O
+,	O
+all	O
+but	O
+two	O
+of	O
+which	O
+occur	O
+at	O
+the	O
+third	O
+position	O
+of	O
+the	O
+affected	O
+codon	O
+.	O
+
+This	O
+observation	O
+provides	O
+biochemical	O
+confirmation	O
+of	O
+the	O
+functional	O
+identity	O
+predicted	O
+on	O
+the	O
+basis	O
+of	O
+previous	O
+genetic	O
+analysis	O
+(	O
+9	O
+)	O
+.	O
+
+A	O
+number	O
+of	O
+DNA	O
+binding	O
+proteins	O
+exhibit	O
+a	O
+common	O
+structural	O
+motif	O
+in	O
+which	O
+two	O
+helices	O
+are	O
+separated	O
+by	O
+a	O
+glycine	O
+residue	O
+(	O
+12	O
+)	O
+.	O
+
+This	O
+motif	O
+is	O
+not	O
+observed	O
+in	O
+the	O
+predicted	O
+secondary	O
+structures	O
+(	O
+30	O
+)	O
+of	O
+the	O
+Plcl	O
+and	O
+P7cl	O
+amino	O
+acid	O
+sequences	O
+.	O
+
+A	O
+sequence	O
+with	O
+some	O
+similarity	O
+to	O
+the	O
+XCro	O
+helix	O
+-	O
+turn	O
+-	O
+helix	O
+region	O
+was	O
+previously	O
+reported	O
+near	O
+the	O
+Nterminus	O
+of	O
+the	O
+PIcI	O
+protein	O
+(	O
+5	O
+)	O
+;	O
+however	O
+,	O
+it	O
+was	O
+noted	O
+that	O
+the	O
+potential	O
+for	O
+helix	O
+formation	O
+is	O
+disrupted	O
+by	O
+the	O
+presence	O
+of	O
+several	O
+prolines	O
+within	O
+the	O
+region	O
+.	O
+
+The	O
+secondary	O
+structure	O
+predicted	O
+for	O
+the	O
+Plcl	O
+and	O
+P7cl	O
+repressor	O
+proteins	O
+(	O
+30	O
+)	O
+does	O
+not	O
+reveal	O
+other	O
+structural	O
+characteristics	O
+(	O
+e	O
+.	O
+g	O
+.	O
+,	O
+Zn	O
+fingers	O
+(	O
+31	O
+)	O
+,	O
+leucine	O
+zippers	O
+(	O
+32	O
+)	O
+,	O
+or	O
+helix	O
+-	O
+loop	O
+-	O
+helix	O
+motifs	O
+(	O
+33	O
+)	O
+)	O
+that	O
+have	O
+been	O
+associated	O
+with	O
+DNA	O
+binding	O
+activity	O
+in	O
+other	O
+systems	O
+.	O
+
+A	O
+search	O
+of	O
+the	O
+GenBank	O
+and	O
+EMBL	O
+databases	O
+does	O
+not	O
+reveal	O
+any	O
+other	O
+known	O
+regulatory	O
+proteins	O
+with	O
+significant	O
+amino	O
+acid	O
+similarity	O
+to	O
+the	O
+Plcl	O
+or	O
+the	O
+P7cl	O
+repressor	O
+sequences	O
+.	O
+
+Since	O
+the	O
+Plcl	O
+repressor	O
+differs	O
+from	O
+most	O
+other	O
+repressors	O
+in	O
+DNA	O
+binding	O
+specificity	O
+(	O
+i	O
+.	O
+e	O
+.	O
+,	O
+in	O
+its	O
+recognition	O
+of	O
+an	O
+asymmetric	O
+operator	O
+sequence	O
+)	O
+,	O
+it	O
+is	O
+not	O
+unexpected	O
+to	O
+find	O
+that	O
+the	O
+protein	O
+does	O
+not	O
+exhibit	O
+common	O
+structural	O
+motifs	O
+at	O
+the	O
+amino	O
+acid	O
+level	O
+.	O
+
+The	O
+cl	O
+-	O
+repressible	O
+promoter	O
+described	O
+in	O
+this	O
+report	O
+is	O
+located	O
+in	O
+a	O
+region	O
+just	O
+upstream	O
+of	O
+the	O
+cl	O
+open	O
+reading	O
+frame	O
+and	O
+is	O
+oriented	O
+in	O
+the	O
+direction	O
+of	O
+cl	O
+.	O
+
+Because	O
+the	O
+promoter	O
+is	O
+present	O
+on	O
+a	O
+multicopy	O
+plasmid	O
+,	O
+it	O
+is	O
+not	O
+possible	O
+to	O
+make	O
+a	O
+direct	O
+calculation	O
+of	O
+promoter	O
+strength	O
+;	O
+however	O
+,	O
+the	O
+values	O
+observed	O
+are	O
+about	O
+five	O
+-	O
+fold	O
+lower	O
+than	O
+the	O
+levels	O
+produced	O
+by	O
+a	O
+derivative	O
+of	O
+pCB192	O
+that	O
+contains	O
+the	O
+plac	O
+promoter	O
+from	O
+pUC19	O
+(	O
+34	O
+)	O
+.	O
+
+Because	O
+sequences	O
+on	O
+both	O
+sides	O
+of	O
+the	O
+BamHI	O
+site	O
+located	O
+upstream	O
+of	O
+cl	O
+are	O
+required	O
+for	O
+promoter	O
+activity	O
+(	O
+Table	O
+2	O
+)	O
+,	O
+we	O
+suggest	O
+that	O
+the	O
+promoter	O
+spans	O
+this	O
+site	O
+.	O
+
+Less	O
+than	O
+10	O
+bps	O
+downstream	O
+of	O
+this	O
+BamHI	O
+site	O
+is	O
+a	O
+heptanucleotide	O
+sequence	O
+(	O
+TATAATG	O
+)	O
+that	O
+is	O
+identical	O
+to	O
+the	O
+-	O
+10	O
+consensus	O
+sequence	O
+for	O
+RNA	O
+polymerase	O
+(	O
+35	O
+)	O
+.	O
+
+If	O
+this	O
+sequence	O
+does	O
+indeed	O
+correspond	O
+to	O
+the	O
+-	O
+10	O
+region	O
+of	O
+the	O
+promoter	O
+,	O
+the	O
+-	O
+35	O
+region	O
+would	O
+be	O
+predicted	O
+to	O
+lie	O
+on	O
+the	O
+other	O
+side	O
+of	O
+the	O
+BamHI	O
+site	O
+in	O
+a	O
+region	O
+that	O
+overlaps	O
+a	O
+known	O
+cI	O
+repressor	O
+binding	O
+site	O
+(	O
+2	O
+-	O
+5	O
+)	O
+.	O
+
+Analysis	O
+of	O
+this	O
+region	O
+does	O
+not	O
+reveal	O
+any	O
+sequences	O
+with	O
+significant	O
+similarity	O
+to	O
+the	O
+-	O
+35	O
+consensus	O
+sequence	O
+.	O
+
+The	O
+best	O
+fit	O
+is	O
+the	O
+sequence	O
+TCTATT	O
+(	O
+Figure	O
+3	O
+)	O
+,	O
+which	O
+matches	O
+only	O
+two	O
+positions	O
+of	O
+the	O
+-	O
+35	O
+consensus	O
+(	O
+TTGACA	O
+)	O
+.	O
+
+The	O
+lack	O
+of	O
+a	O
+strong	O
+-	O
+35	O
+region	O
+is	O
+often	O
+observed	O
+with	O
+genes	O
+that	O
+require	O
+an	O
+activator	O
+.	O
+
+Although	O
+a	O
+pentanucleotide	O
+sequence	O
+corresponding	O
+to	O
+the	O
+conserved	O
+portion	O
+of	O
+the	O
+CRP	O
+protein	O
+consensus	O
+binding	O
+site	O
+(	O
+36	O
+)	O
+
+7678	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+is	O
+located	O
+just	O
+upstream	O
+of	O
+the	O
+predicted	O
+-	O
+35	O
+region	O
+(	O
+at	O
+position	O
+91	O
+;	O
+Figure	O
+3	O
+)	O
+,	O
+a	O
+role	O
+for	O
+CRP	O
+-	O
+mediated	O
+activation	O
+in	O
+cl	O
+expression	O
+has	O
+not	O
+previously	O
+been	O
+described	O
+.	O
+
+The	O
+orientation	O
+of	O
+the	O
+promoter	O
+and	O
+its	O
+cl	O
+-	O
+repressible	O
+character	O
+raise	O
+the	O
+possibility	O
+that	O
+cl	O
+expression	O
+is	O
+autoregulatory	O
+.	O
+
+If	O
+this	O
+is	O
+so	O
+,	O
+one	O
+potential	O
+activator	O
+would	O
+be	O
+the	O
+cl	O
+repressor	O
+itself	O
+.	O
+
+Expression	O
+cannot	O
+be	O
+absolutely	O
+dependent	O
+on	O
+cl	O
+-	O
+mediated	O
+activation	O
+,	O
+however	O
+,	O
+because	O
+the	O
+cloned	O
+promoter	O
+exhibits	O
+significant	O
+activity	O
+in	O
+the	O
+absence	O
+of	O
+the	O
+cl	O
+gene	O
+(	O
+Table	O
+2	O
+)	O
+.	O
+
+Under	O
+the	O
+conditions	O
+reported	O
+here	O
+,	O
+the	O
+presence	O
+of	O
+the	O
+cl	O
+gene	O
+results	O
+in	O
+a	O
+decrease	O
+rather	O
+than	O
+an	O
+increase	O
+in	O
+lacZ	O
+expression	O
+;	O
+however	O
+,	O
+these	O
+observations	O
+do	O
+not	O
+rule	O
+out	O
+a	O
+potential	O
+activator	O
+role	O
+for	O
+the	O
+cl	O
+protein	O
+,	O
+since	O
+the	O
+ratios	O
+of	O
+repressor	O
+and	O
+operator	O
+provided	O
+by	O
+the	O
+multicopy	O
+plasmids	O
+may	O
+not	O
+be	O
+optimal	O
+for	O
+activation	O
+.	O
+
+Physiologically	O
+,	O
+the	O
+role	O
+of	O
+additional	O
+repressor	O
+binding	O
+sites	O
+in	O
+regulating	O
+cl	O
+expression	O
+also	O
+cannot	O
+be	O
+discounted	O
+.	O
+
+Three	O
+potential	O
+operator	O
+sites	O
+have	O
+been	O
+identified	O
+several	O
+hundred	O
+bps	O
+upstream	O
+of	O
+the	O
+cI	O
+open	O
+reading	O
+frame	O
+(	O
+2	O
+-	O
+5	O
+)	O
+;	O
+one	O
+or	O
+more	O
+of	O
+these	O
+could	O
+be	O
+involved	O
+(	O
+possibly	O
+through	O
+a	O
+DNA	O
+looping	O
+mechanism	O
+;	O
+37	O
+)	O
+in	O
+the	O
+activation	O
+or	O
+repression	O
+of	O
+cl	O
+expression	O
+during	O
+phage	O
+growth	O
+.	O
+
+A	O
+cl	O
+-	O
+repressible	O
+promoter	O
+oriented	O
+in	O
+the	O
+direction	O
+of	O
+cl	O
+was	O
+previously	O
+reported	O
+(	O
+38	O
+)	O
+to	O
+be	O
+located	O
+entirely	O
+within	O
+PlBamHI	O
+-	O
+9	O
+,	O
+a	O
+fragment	O
+located	O
+upstream	O
+of	O
+cl	O
+which	O
+is	O
+bracketed	O
+by	O
+the	O
+BamHI	O
+site	O
+within	O
+pBCB2	O
+.	O
+
+13	O
+.	O
+
+Because	O
+sequences	O
+on	O
+both	O
+sides	O
+of	O
+this	O
+BamHI	O
+site	O
+are	O
+required	O
+for	O
+the	O
+activity	O
+of	O
+the	O
+promoter	O
+in	O
+pBCB2	O
+.	O
+13	O
+,	O
+we	O
+suggest	O
+that	O
+the	O
+previously	O
+identified	O
+promoter	O
+is	O
+distinct	O
+from	O
+the	O
+one	O
+reported	O
+here	O
+.	O
+
+The	O
+promoter	O
+from	O
+BamHI	O
+-	O
+9	O
+could	O
+correspond	O
+to	O
+a	O
+consensus	O
+promoter	O
+sequence	O
+that	O
+is	O
+situated	O
+about	O
+500	O
+bps	O
+upstream	O
+of	O
+cl	O
+and	O
+overlaps	O
+a	O
+cl	O
+repressor	O
+binding	O
+site	O
+(	O
+2	O
+)	O
+.	O
+
+If	O
+so	O
+,	O
+cl	O
+expression	O
+is	O
+likely	O
+to	O
+be	O
+controlled	O
+by	O
+more	O
+than	O
+one	O
+promoter	O
+.	O
+
+Located	O
+between	O
+this	O
+promoter	O
+sequence	O
+and	O
+the	O
+promoter	O
+encoded	O
+on	O
+pBCB2	O
+.	O
+
+13	O
+is	O
+an	O
+open	O
+reading	O
+frame	O
+whose	O
+product	O
+(	O
+termed	O
+coi	O
+,	O
+or	O
+c	O
+-	O
+one	O
+inactivator	O
+)	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+establishment	O
+of	O
+lytic	O
+growth	O
+(	O
+1	O
+,	O
+39	O
+;	O
+B	O
+.	O
+R	O
+.	O
+Baumstark	O
+,	O
+unpublished	O
+results	O
+)	O
+.	O
+
+It	O
+has	O
+been	O
+suggested	O
+(	O
+2	O
+)	O
+that	O
+the	O
+decision	O
+to	O
+enter	O
+lytic	O
+or	O
+lysogenic	O
+growth	O
+is	O
+influenced	O
+by	O
+the	O
+level	O
+of	O
+transcription	O
+initiated	O
+from	O
+the	O
+distal	O
+promoter	O
+(	O
+which	O
+would	O
+transcribe	O
+coi	O
+prior	O
+to	O
+the	O
+transcription	O
+of	O
+cl	O
+)	O
+relative	O
+to	O
+that	O
+of	O
+the	O
+promoter	O
+located	O
+immediately	O
+upstream	O
+of	O
+the	O
+cl	O
+gene	O
+(	O
+which	O
+would	O
+transcribe	O
+only	O
+ci	O
+)	O
+.	O
+
+A	O
+32	O
+-	O
+nucleotide	O
+hyphenated	O
+inverted	O
+repeat	O
+sequence	O
+is	O
+located	O
+just	O
+upstream	O
+of	O
+the	O
+cl	O
+open	O
+reading	O
+frame	O
+(	O
+positions	O
+146	O
+-	O
+188	O
+;	O
+Figure	O
+3	O
+)	O
+.	O
+
+It	O
+is	O
+not	O
+currently	O
+known	O
+whether	O
+this	O
+sequence	O
+has	O
+any	O
+regulatory	O
+effect	O
+on	O
+cl	O
+expression	O
+.	O
+
+Conceivably	O
+,	O
+the	O
+sequence	O
+could	O
+serve	O
+as	O
+a	O
+recognition	O
+site	O
+for	O
+an	O
+as	O
+-	O
+yet	O
+-	O
+unidentified	O
+regulatory	O
+protein	O
+.	O
+
+Alternatively	O
+,	O
+it	O
+may	O
+affect	O
+the	O
+secondary	O
+structure	O
+of	O
+the	O
+messenger	O
+RNA	O
+.	O
+
+A	O
+transcript	O
+extending	O
+from	O
+a	O
+promoter	O
+located	O
+upstream	O
+of	O
+the	O
+putative	O
+coi	O
+open	O
+reading	O
+frame	O
+would	O
+be	O
+capable	O
+of	O
+forming	O
+a	O
+stable	O
+stem	O
+-	O
+loop	O
+structure	O
+containing	O
+16	O
+bps	O
+with	O
+a	O
+single	O
+bp	O
+mismatch	O
+(	O
+AG	O
+=	O
+-	O
+33	O
+.	O
+6	O
+Kcal	O
+)	O
+of	O
+this	O
+inverted	O
+repeat	O
+sequence	O
+.	O
+
+Such	O
+a	O
+structure	O
+could	O
+potentially	O
+serve	O
+as	O
+a	O
+recognition	O
+site	O
+for	O
+a	O
+regulatory	O
+factor	O
+or	O
+,	O
+alternatively	O
+,	O
+could	O
+mask	O
+such	O
+a	O
+site	O
+.	O
+
+On	O
+the	O
+other	O
+hand	O
+,	O
+transcription	O
+originating	O
+from	O
+the	O
+promoter	O
+spanning	O
+the	O
+BamHI	O
+site	O
+just	O
+upstream	O
+of	O
+cl	O
+would	O
+start	O
+at	O
+a	O
+site	O
+within	O
+the	O
+inverted	O
+repeat	O
+sequence	O
+,	O
+forming	O
+a	O
+comparatively	O
+less	O
+stable	O
+stem	O
+-	O
+loop	O
+structure	O
+of	O
+about	O
+8	O
+bps	O
+.	O
+
+The	O
+role	O
+of	O
+the	O
+inverted	O
+repeat	O
+region	O
+in	O
+the	O
+regulation	O
+of	O
+cl	O
+expression	O
+is	O
+currently	O
+under	O
+investigation	O
+.	O
+
+ACKNOWLEDGEMENTS	O
+
+We	O
+thank	O
+Heinz	O
+Schuster	O
+for	O
+his	O
+review	O
+of	O
+the	O
+manuscript	O
+.	O
+
+This	O
+work	O
+was	O
+supported	O
+by	O
+National	O
+Science	O
+Foundation	O
+grant	O
+DMB	O
+-	O
+8704146	O
+.	O
+
+7679	O
+
+Nucleic	O
+Acids	O
+Research	O
+
+Abbreviations	O
+:	O
+bp	O
+,	O
+basepairs	O
+;	O
+kb	O
+,	O
+kilobase	O
+pairs	O
+;	O
+X	O
+-	O
+Gal	O
+,	O
+5	O
+-	O
+Bromo	O
+-	O
+4	O
+-	O
+Chloro	O
+-	O
+3	O
+-	O
+indolylbeta	O
+-	O
+D	O
+-	O
+galactopyranoside	O
+.	O
+
+*	O
+To	O
+whom	O
+correspondence	O
+should	O
+be	O
+addressed	O
+
+REFERENCES	O
+
+1	O
+.	O
+
+Yarmolinsky	O
+,	O
+M	O
+.	O
+B	O
+.	O
+,	O
+and	O
+Steinberg	O
+,	O
+N	O
+.	O
+
+(	O
+1988	O
+)	O
+.	O
+
+In	O
+Calendar	O
+,	O
+R	O
+.	O
+,	O
+(	O
+ed	O
+.	O
+)	O
+,	O
+The	O
+Bacteriophages	O
+,	O
+Plenum	O
+Publishing	O
+
+Corp	O
+.	O
+,	O
+NY	O
+,	O
+Vol	O
+.	O
+
+1	O
+,	O
+pp	O
+.	O
+
+291	O
+-	O
+438	O
+.	O
+
+2	O
+.	O
+
+Baumstark	O
+,	O
+B	O
+.	O
+R	O
+.	O
+,	O
+Stovall	O
+,	O
+S	O
+.	O
+R	O
+.	O
+,	O
+and	O
+Ashkar	O
+,	O
+S	O
+.	O
+
+(	O
+1987	O
+)	O
+.	O
+
+Virology	O
+156	O
+,	O
+404	O
+-	O
+413	O
+.	O
+
+3	O
+.	O
+
+Dreiseikelmann	O
+,	O
+B	O
+.	O
+,	O
+Velleman	O
+,	O
+M	O
+.	O
+,	O
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+Schuster	O
+,	O
+H	O
+.	O
+
+(	O
+1988	O
+)	O
+.	O
+
+J	O
+.	O
+
+Biol	O
+.	O
+
+Chem	O
+.	O
+
+263	O
+,	O
+1391	O
+-	O
+1397	O
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+
+4	O
+.	O
+
+Heinrich	O
+,	O
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+.	O
+,	O
+Riedel	O
+,	O
+H	O
+.	O
+-	O
+D	O
+.	O
+,	O
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+,	O
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+.	O
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+.	O
+,	O
+Kimura	O
+,	O
+M	O
+.	O
+,	O
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+Schuster	O
+,	O
+H	O
+.	O
+
+(	O
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+)	O
+.	O
+
+Nucleic	O
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+Res	O
+,	O
+
+this	O
+volume	O
+.	O
+
+5	O
+.	O
+
+Eliason	O
+,	O
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+L	O
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+,	O
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+,	O
+N	O
+.	O
+
+(	O
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+)	O
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+
+J	O
+.	O
+
+Mol	O
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+
+Biol	O
+.	O
+
+198	O
+,	O
+281	O
+-	O
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+
+6	O
+.	O
+
+Velleman	O
+,	O
+M	O
+.	O
+,	O
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+,	O
+B	O
+.	O
+,	O
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+,	O
+H	O
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+
+(	O
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+)	O
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+
+Proc	O
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+
+Natl	O
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+Acad	O
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+
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+USA	O
+84	O
+,	O
+5570	O
+-	O
+5574	O
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+7	O
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+Citron	O
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+,	O
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+(	O
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+J	O
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+Chem	O
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+264	O
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+8	O
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+Chadwick	O
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+9	O
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+(	O
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+Virology	O
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+10	O
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+
+Wandersman	O
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+(	O
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+11	O
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+(	O
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+Virology	O
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+12	O
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+(	O
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+Ann	O
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+53	O
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+(	O
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+14	O
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+Schneider	O
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+(	O
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+
+Methods	O
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+153	O
+,	O
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+15	O
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+Smith	O
+,	O
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+(	O
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+Nature	O
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+238	O
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+16	O
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+(	O
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+17	O
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+(	O
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+(	O
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+19	O
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+20	O
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+(	O
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+21	O
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+Schneider	O
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+(	O
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+(	O
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+137	O
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+23	O
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+Miller	O
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+(	O
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+Harbor	O
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+352	O
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+
+24	O
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+Guyer	O
+,	O
+R	O
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+(	O
+1978	O
+)	O
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+
+J	O
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+
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+
+Biol	O
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+126	O
+,	O
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+25	O
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+Devlin	O
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+(	O
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+)	O
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+
+Virology	O
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+,	O
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+
+26	O
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+
+Sanger	O
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+,	O
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+,	O
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+,	O
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+.	O
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+
+(	O
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+)	O
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+
+Proc	O
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+
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+
+Sci	O
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+
+USA	O
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+,	O
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+27	O
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+
+DeVries	O
+,	O
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+,	O
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+,	O
+G	O
+.	O
+
+(	O
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+Proc	O
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+28	O
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+Heilmann	O
+,	O
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+,	O
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+R	O
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+,	O
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+(	O
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+Mol	O
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+
+Gen	O
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+Genet	O
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+178	O
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+29	O
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+Shine	O
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+
+(	O
+1974	O
+)	O
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+
+Proc	O
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+Natl	O
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+
+Acad	O
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+Sci	O
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+USA	O
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+,	O
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+-	O
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+30	O
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+
+Chou	O
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+P	O
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+Y	O
+.	O
+,	O
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+,	O
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+
+(	O
+1978	O
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+
+Adv	O
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+
+Enzymol	O
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+
+47	O
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+31	O
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+Berg	O
+,	O
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+.	O
+
+(	O
+1986	O
+)	O
+.	O
+
+Nature	O
+319	O
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+-	O
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+
+32	O
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+Landschultz	O
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+,	O
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+L	O
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+
+(	O
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+)	O
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+
+Science	O
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+33	O
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+Murre	O
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+
+Cell	O
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+
+34	O
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+
+Anderson	O
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+,	O
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+,	O
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+
+(	O
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+)	O
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+
+J	O
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+
+Bacteriol	O
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+
+170	O
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+
+35	O
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+Rosenberg	O
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+
+(	O
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+Annu	O
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+Rev	O
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+Genet	O
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+13	O
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+
+36	O
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+
+Ebright	O
+,	O
+R	O
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+H	O
+.	O
+,	O
+Cossart	O
+,	O
+P	O
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+,	O
+Gicquel	O
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+,	O
+B	O
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+,	O
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+Beckwith	O
+,	O
+J	O
+.	O
+
+(	O
+1984	O
+)	O
+.	O
+
+Nature	O
+311	O
+,	O
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+-	O
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+
+37	O
+.	O
+
+Ptashne	O
+,	O
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+
+(	O
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+)	O
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+
+Nature	O
+322	O
+,	O
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+-	O
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+
+38	O
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+
+Stemnberg	O
+,	O
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+,	O
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+,	O
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+.	O
+
+(	O
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+)	O
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+
+Annu	O
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+
+Rev	O
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+
+Genet	O
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+
+17	O
+,	O
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+39	O
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+
+Scott	O
+,	O
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+.	O
+
+(	O
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+
+Curr	O
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+Top	O
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+
+Microbiol	O
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+Immunol	O
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+90	O
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+49	O
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+This	O
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+,	O
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+converted	O
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+Down	O
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+Abstract	O
+
+Background	O
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+The	O
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+Cardiac	O
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+,	O
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+However	O
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+Thus	O
+,	O
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+/	O
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+
+Results	O
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+We	O
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+-	O
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+/	O
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+cell	O
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+Infection	O
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+neonatal	O
+cardiomyocytes	O
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+a	O
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+against	O
+the	O
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+/	O
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+M6P	O
+/	O
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+mRNA	O
+,	O
+as	O
+determined	O
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+-	O
+PCR	O
+and	O
+Ribonuclease	O
+Protection	O
+Assay	O
+(	O
+RPA	O
+)	O
+.	O
+
+M6P	O
+-	O
+containing	O
+protein	O
+binding	O
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+as	O
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+/	O
+IGF2R	O
+-	O
+mediated	O
+internalization	O
+of	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+were	O
+lower	O
+in	O
+the	O
+ribozyme	O
+-	O
+treated	O
+cells	O
+than	O
+the	O
+control	O
+myocytes	O
+,	O
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+that	O
+the	O
+number	O
+of	O
+functional	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+the	O
+ribozyme	O
+treated	O
+cells	O
+was	O
+reduced	O
+.	O
+
+Accordingly	O
+,	O
+a	O
+marked	O
+increase	O
+in	O
+cell	O
+proliferation	O
+and	O
+a	O
+reduced	O
+cell	O
+susceptibility	O
+to	O
+hypoxia	O
+-	O
+and	O
+TNF	O
+-	O
+induced	O
+apoptosis	O
+were	O
+observed	O
+in	O
+the	O
+ribozyme	O
+-	O
+treated	O
+cells	O
+.	O
+
+Conclusions	O
+
+These	O
+findings	O
+suggest	O
+that	O
+M6P	O
+/	O
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+may	O
+play	O
+a	O
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+in	O
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+and	O
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+
+Down	O
+regulation	O
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+this	O
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+in	O
+cardiac	O
+tissues	O
+might	O
+be	O
+a	O
+new	O
+approach	O
+to	O
+prevention	O
+of	O
+cell	O
+death	O
+or	O
+promotion	O
+of	O
+mitogenesis	O
+for	O
+certain	O
+heart	O
+diseases	O
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+
+Background	O
+
+The	O
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+6	O
+-	O
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+/	O
+insulin	O
+-	O
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+(	O
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+/	O
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+interacts	O
+with	O
+multiple	O
+ligands	O
+,	O
+some	O
+of	O
+which	O
+are	O
+important	O
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+[	O
+1	O
+]	O
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+The	O
+M6P	O
+/	O
+IGF2R	O
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+in	O
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+degradation	O
+of	O
+IGF	O
+-	O
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+,	O
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+acting	O
+through	O
+the	O
+IGF	O
+-	O
+I	O
+receptor	O
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+stimulate	O
+cell	O
+proliferation	O
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+2	O
+]	O
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+
+The	O
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+/	O
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+-	O
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+,	O
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+for	O
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+cell	O
+types	O
+.	O
+
+This	O
+receptor	O
+is	O
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+in	O
+the	O
+binding	O
+,	O
+transport	O
+and	O
+activation	O
+of	O
+newly	O
+-	O
+synthesized	O
+lysosomal	O
+enzymes	O
+,	O
+such	O
+as	O
+cathepsins	O
+[	O
+4	O
+,	O
+5	O
+]	O
+,	O
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+have	O
+been	O
+recently	O
+implicated	O
+in	O
+the	O
+induction	O
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+apoptosis	O
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+6	O
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+
+On	O
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+basis	O
+of	O
+these	O
+functions	O
+,	O
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+/	O
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+been	O
+proposed	O
+to	O
+play	O
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+role	O
+in	O
+regulation	O
+of	O
+cell	O
+growth	O
+and	O
+apoptosis	O
+[	O
+7	O
+]	O
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+
+Apoptosis	O
+,	O
+or	O
+programmed	O
+cell	O
+death	O
+,	O
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+regulated	O
+process	O
+used	O
+to	O
+remove	O
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+,	O
+hazardous	O
+or	O
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+cells	O
+,	O
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+for	O
+the	O
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+,	O
+maintenance	O
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+an	O
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+However	O
+,	O
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+apoptosis	O
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+also	O
+been	O
+shown	O
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+contribute	O
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+human	B
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+
+In	O
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+,	O
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+markers	O
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+apoptosis	O
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+been	O
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+including	O
+myocardial	O
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+
+This	O
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+contributes	O
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+cardiomyocyte	O
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+subsequent	O
+cardiac	O
+dysfunction	O
+in	O
+these	O
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+
+A	O
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+and	O
+include	O
+insulin	O
+-	O
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+-	O
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+-	O
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+-	O
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+-	O
+2	O
+family	O
+[	O
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+There	O
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+that	O
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+However	O
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+Several	O
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+
+Cardiac	O
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+M6P	O
+/	O
+IGF2R	O
+and	O
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+a	O
+homologous	O
+deletion	O
+of	O
+the	O
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+/	O
+IGF2R	O
+gene	O
+manifest	O
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+hyperplasia	O
+due	O
+to	O
+an	O
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+cell	O
+number	O
+[	O
+9	O
+,	O
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+]	O
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+that	O
+the	O
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+/	O
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+to	O
+suppress	O
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+
+It	O
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+been	O
+shown	O
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+,	O
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+suppressor	O
+whose	O
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+the	O
+binding	O
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+-	O
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+/	O
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+,	O
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+heart	O
+failure	O
+[	O
+11	O
+]	O
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+
+Additional	O
+evidence	O
+for	O
+the	O
+involvement	O
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+M6P	O
+/	O
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+studies	O
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+
+It	O
+has	O
+been	O
+shown	O
+that	O
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+/	O
+IGF2R	O
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+is	O
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+in	O
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+loss	O
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+(	O
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+/	O
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+have	O
+been	O
+found	O
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+,	O
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+the	O
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+[	O
+12	O
+-	O
+15	O
+]	O
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+
+Although	O
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+studies	O
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+the	O
+effect	O
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+M6P	O
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+IGF2R	O
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+-	O
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+-	O
+regulation	O
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+this	O
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+protein	O
+leads	O
+to	O
+cellular	O
+protection	O
+against	O
+apoptosis	O
+.	O
+
+Ribozymes	O
+are	O
+catalytic	O
+RNA	O
+molecules	O
+that	O
+cleave	O
+a	O
+complementary	O
+mRNA	O
+sequence	O
+[	O
+16	O
+]	O
+,	O
+thereby	O
+inactivating	O
+specific	O
+mRNAs	O
+and	O
+suppressing	O
+gene	O
+expression	O
+in	O
+vitro	O
+and	O
+in	O
+vivo	O
+[	O
+17	O
+,	O
+18	O
+]	O
+.	O
+
+Ribozymes	O
+have	O
+been	O
+shown	O
+to	O
+be	O
+highly	O
+specific	O
+,	O
+efficient	O
+and	O
+stable	O
+.	O
+
+They	O
+can	O
+be	O
+packaged	O
+into	O
+viral	O
+vectors	O
+to	O
+enhance	O
+transfer	O
+into	O
+cells	O
+and	O
+to	O
+achieve	O
+longer	O
+expression	O
+compared	O
+with	O
+naked	O
+oligonucleotides	O
+.	O
+
+In	O
+the	O
+present	O
+study	O
+,	O
+we	O
+employed	O
+ribozyme	O
+technology	O
+to	O
+study	O
+the	O
+role	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+regulation	O
+of	O
+cardiac	O
+myocyte	O
+cell	O
+growth	O
+.	O
+
+A	O
+hammerhead	O
+ribozyme	O
+against	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+was	O
+constructed	O
+and	O
+packaged	O
+in	O
+an	O
+adenoviral	O
+vector	O
+.	O
+
+We	O
+then	O
+examined	O
+the	O
+effect	O
+of	O
+ribozyme	O
+-	O
+mediated	O
+down	O
+-	O
+regulation	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+on	O
+cell	O
+growth	O
+and	O
+hypoxia	O
+-	O
+and	O
+TNF	O
+-	O
+induced	O
+apoptosis	O
+.	O
+
+Results	O
+
+Cleavage	O
+reaction	O
+of	O
+the	O
+ribozyme	O
+in	O
+vitro	O
+
+The	O
+M6P	O
+/	O
+IGF2R	O
+ribozyme	O
+we	O
+constructed	O
+has	O
+13	O
+-	O
+bp	O
+binding	O
+arms	O
+complementary	O
+to	O
+the	O
+target	O
+site	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+,	O
+and	O
+a	O
+catalytic	O
+core	O
+(	O
+Fig	O
+.	O
+1A	O
+)	O
+.	O
+
+To	O
+evaluate	O
+the	O
+bioactivity	O
+of	O
+the	O
+ribozyme	O
+and	O
+the	O
+accessibility	O
+of	O
+the	O
+target	O
+site	O
+,	O
+a	O
+cleavage	O
+reaction	O
+was	O
+performed	O
+in	O
+vitro	O
+.	O
+
+The	O
+substrates	O
+,	O
+[	O
+alpha	O
+-	O
+32P	O
+]	O
+labeled	O
+RNA	O
+transcripts	O
+containing	O
+45	O
+bp	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+or	O
+an	O
+unmatched	O
+sequence	O
+,	O
+were	O
+incubated	O
+with	O
+the	O
+ribozyme	O
+as	O
+described	O
+(	O
+see	O
+Materials	O
+and	O
+Methods	O
+)	O
+.	O
+
+The	O
+ribozyme	O
+cleaved	O
+only	O
+the	O
+specific	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+into	O
+the	O
+expected	O
+products	O
+.	O
+
+In	O
+the	O
+assay	O
+of	O
+time	O
+course	O
+,	O
+the	O
+hammerhead	O
+ribozyme	O
+was	O
+able	O
+to	O
+cleave	O
+24	O
+.	O
+2	O
+%	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+target	O
+within	O
+10	O
+minutes	O
+of	O
+incubation	O
+,	O
+50	O
+.	O
+3	O
+%	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+target	O
+within	O
+40	O
+minutes	O
+of	O
+incubation	O
+,	O
+and	O
+by	O
+640	O
+minutes	O
+,	O
+80	O
+.	O
+8	O
+%	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+target	O
+was	O
+converted	O
+to	O
+the	O
+expected	O
+products	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+This	O
+ribozyme	O
+did	O
+not	O
+digest	O
+the	O
+unmatched	O
+sequence	O
+(	O
+Fig	O
+.	O
+1B	O
+)	O
+.	O
+
+These	O
+results	O
+indicate	O
+a	O
+high	O
+efficiency	O
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+specificity	O
+of	O
+the	O
+ribozyme	O
+in	O
+vitro	O
+.	O
+
+Ribozymes	O
+down	O
+-	O
+regulate	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+in	O
+cardiac	O
+myocytes	O
+
+To	O
+examine	O
+the	O
+ability	O
+of	O
+the	O
+ribozyme	O
+to	O
+reduce	O
+levels	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+in	O
+cultured	O
+cardiac	O
+myocytes	O
+,	O
+total	O
+RNA	O
+was	O
+extracted	O
+from	O
+cells	O
+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+or	O
+Ad	O
+-	O
+GFP	O
+,	O
+and	O
+subjected	O
+to	O
+RT	O
+-	O
+PCR	O
+using	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+specific	O
+primers	O
+.	O
+
+Primers	O
+specific	O
+for	O
+beta	O
+-	O
+actin	O
+were	O
+added	O
+to	O
+a	O
+parallel	O
+reaction	O
+to	O
+serve	O
+as	O
+an	O
+internal	O
+standard	O
+.	O
+
+Cells	O
+were	O
+used	O
+4	O
+days	O
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+infection	O
+,	O
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+average	O
+infection	O
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+70	O
+-	O
+80	O
+%	O
+(	O
+for	O
+which	O
+a	O
+viral	O
+dose	O
+used	O
+had	O
+minimal	O
+cytotoxicity	O
+)	O
+.	O
+
+The	O
+RT	O
+-	O
+PCR	O
+product	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+was	O
+856	O
+bp	O
+,	O
+and	O
+the	O
+beta	O
+-	O
+actin	O
+product	O
+was	O
+285	O
+bp	O
+.	O
+
+As	O
+shown	O
+in	O
+Fig	O
+.	O
+
+2A	O
+,	O
+the	O
+Ad	O
+-	O
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+/	O
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+-	O
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+-	O
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+a	O
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+level	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+than	O
+Ad	O
+-	O
+GFP	O
+-	O
+infected	O
+cells	O
+,	O
+with	O
+a	O
+reduction	O
+of	O
+about	O
+50	O
+%	O
+.	O
+
+This	O
+result	O
+was	O
+confirmed	O
+by	O
+ribonuclease	O
+protection	O
+assay	O
+(	O
+RPA	O
+)	O
+,	O
+in	O
+which	O
+GAPDH	O
+was	O
+used	O
+as	O
+a	O
+control	O
+(	O
+Fig	O
+.	O
+2C	O
+&	O
+2D	O
+)	O
+.	O
+
+There	O
+was	O
+no	O
+significant	O
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+the	O
+level	O
+of	O
+M6P	O
+/	O
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+mRNA	O
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+-	O
+GFP	O
+-	O
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+cells	O
+and	O
+uninfected	O
+cells	O
+(	O
+data	O
+not	O
+shown	O
+)	O
+,	O
+indicating	O
+that	O
+infection	O
+with	O
+the	O
+adenovirus	O
+itself	O
+did	O
+not	O
+alter	O
+the	O
+endogenous	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+level	O
+.	O
+
+The	O
+results	O
+demonstrated	O
+that	O
+the	O
+ribozyme	O
+was	O
+highly	O
+effective	O
+in	O
+suppressing	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+in	O
+cultured	O
+cardiac	O
+myocytes	O
+.	O
+
+Effect	O
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+ribozyme	O
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+on	O
+the	O
+functional	O
+activity	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+
+To	O
+determine	O
+the	O
+effect	O
+of	O
+the	O
+ribozyme	O
+on	O
+the	O
+functional	O
+activity	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+,	O
+binding	O
+and	O
+internalization	O
+of	O
+exogenous	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+was	O
+measured	O
+in	O
+cells	O
+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+.	O
+
+As	O
+shown	O
+in	O
+Fig	O
+.	O
+
+3A	O
+,	O
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+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
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+a	O
+54	O
+%	O
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+in	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+internalization	O
+when	O
+compared	O
+with	O
+the	O
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+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+)	O
+.	O
+
+We	O
+also	O
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+the	O
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+-	O
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+M6P	O
+/	O
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+the	O
+M6P	O
+-	O
+bearing	O
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+,	O
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+-	O
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+,	O
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+.	O
+
+The	O
+results	O
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+that	O
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+maximal	O
+M6P	O
+-	O
+binding	O
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+of	O
+cells	O
+treated	O
+with	O
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+about	O
+50	O
+%	O
+less	O
+than	O
+that	O
+of	O
+controls	O
+(	O
+Fig	O
+.	O
+3B	O
+)	O
+.	O
+
+Furthermore	O
+,	O
+we	O
+assessed	O
+the	O
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+of	O
+cells	O
+to	O
+internalize	O
+exogenous	O
+beta	O
+-	O
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+after	O
+treatment	O
+with	O
+ribozyme	O
+.	O
+
+Similarly	O
+,	O
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+beta	O
+-	O
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+-	O
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+%	O
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+cells	O
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+Fig	O
+.	O
+3C	O
+)	O
+.	O
+
+These	O
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+confirm	O
+that	O
+the	O
+number	O
+of	O
+functional	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+ribozyme	O
+-	O
+treated	O
+cells	O
+was	O
+reduced	O
+.	O
+
+Adenoviral	O
+delivery	O
+of	O
+ribozymes	O
+increases	O
+the	O
+proliferation	O
+of	O
+cardiac	O
+myocytes	O
+
+We	O
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+the	O
+ribozyme	O
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+cultured	O
+neonatal	O
+rat	B
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+.	O
+
+Morphological	O
+evaluation	O
+showed	O
+a	O
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+difference	O
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+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+-	O
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+cells	O
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+-	O
+expressing	O
+cells	O
+formed	O
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+and	O
+more	O
+spread	O
+colonies	O
+(	O
+Fig	O
+.	O
+4	O
+)	O
+.	O
+
+Assessment	O
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+cell	O
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+activity	O
+by	O
+the	O
+MTT	O
+assay	O
+and	O
+counts	O
+of	O
+viable	O
+cells	O
+showed	O
+that	O
+the	O
+number	O
+of	O
+cardiac	O
+myocytes	O
+in	O
+ribozyme	O
+-	O
+expressing	O
+cultures	O
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+than	O
+in	O
+control	O
+cultures	O
+(	O
+Fig	O
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+5	O
+)	O
+.	O
+
+These	O
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+treatment	O
+with	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+ribozyme	O
+can	O
+promote	O
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+.	O
+
+Effect	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+-	O
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+
+We	O
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+effects	O
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+ribozyme	O
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+-	O
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+hypoxia	O
+-	O
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+apoptosis	O
+of	O
+cultured	O
+cardiac	O
+myocytes	O
+.	O
+
+After	O
+a	O
+24	O
+hr	O
+challenge	O
+with	O
+hypoxia	O
+,	O
+the	O
+number	O
+of	O
+apoptotic	O
+cells	O
+in	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+expressing	O
+cultures	O
+was	O
+38	O
+%	O
+lower	O
+than	O
+in	O
+control	O
+cultures	O
+as	O
+determined	O
+by	O
+Hoechst	O
+staining	O
+(	O
+which	O
+highlights	O
+the	O
+nuclei	O
+of	O
+apoptotic	O
+cells	O
+)	O
+and	O
+ELISA	O
+(	O
+Fig	O
+.	O
+6A	O
+,	O
+7A	O
+)	O
+.	O
+
+MTT	O
+analysis	O
+showed	O
+that	O
+the	O
+number	O
+of	O
+viable	O
+cells	O
+in	O
+ribozyme	O
+-	O
+treated	O
+cultures	O
+was	O
+40	O
+%	O
+higher	O
+than	O
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+control	O
+cultures	O
+(	O
+Fig	O
+.	O
+7A	O
+)	O
+.	O
+
+After	O
+treatment	O
+with	O
+TNF	O
+-	O
+alpha	O
+,	O
+as	O
+shown	O
+in	O
+Fig	O
+.	O
+
+6B	O
+,	O
+a	O
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+number	O
+of	O
+control	O
+cells	O
+underwent	O
+apoptosis	O
+,	O
+as	O
+indicated	O
+by	O
+morphological	O
+changes	O
+(	O
+small	O
+round	O
+shape	O
+)	O
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+bright	O
+blue	O
+nuclear	O
+staining	O
+.	O
+
+There	O
+were	O
+significantly	O
+more	O
+apoptotic	O
+cells	O
+in	O
+control	O
+cultures	O
+than	O
+in	O
+cultures	O
+expressing	O
+the	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
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+.	O
+
+The	O
+number	O
+of	O
+apoptotic	O
+cells	O
+,	O
+as	O
+measured	O
+by	O
+the	O
+cell	O
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+assay	O
+,	O
+in	O
+cultures	O
+infected	O
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+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+was	O
+significantly	O
+(	O
+about	O
+40	O
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+)	O
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+than	O
+in	O
+cultures	O
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+with	O
+Ad	O
+-	O
+GFP	O
+(	O
+Fig	O
+.	O
+7B	O
+)	O
+.	O
+
+Accordingly	O
+,	O
+the	O
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+cells	O
+,	O
+as	O
+measured	O
+by	O
+MTT	O
+analysis	O
+,	O
+in	O
+cultures	O
+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
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+significantly	O
+(	O
+about	O
+45	O
+%	O
+)	O
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+than	O
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+with	O
+Ad	O
+-	O
+GFP	O
+(	O
+Fig	O
+.	O
+7B	O
+)	O
+.	O
+
+These	O
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+the	O
+hypothesis	O
+that	O
+decreasing	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+by	O
+ribozyme	O
+treatment	O
+can	O
+reduce	O
+cell	O
+apoptosis	O
+.	O
+
+Discussion	O
+
+Some	O
+62	O
+,	O
+000	O
+,	O
+000	O
+Americans	O
+have	O
+one	O
+or	O
+more	O
+types	O
+of	O
+cardiovascular	O
+disease	O
+(	O
+CVD	O
+)	O
+and	O
+CVD	O
+is	O
+the	O
+leading	O
+cause	O
+(	O
+40	O
+.	O
+1	O
+%	O
+)	O
+of	O
+death	O
+in	O
+the	O
+United	O
+States	O
+.	O
+
+Myocardial	O
+infarction	O
+and	O
+heart	O
+failure	O
+,	O
+conditions	O
+accompanied	O
+by	O
+cardiac	O
+myocyte	O
+apoptosis	O
+,	O
+represent	O
+23	O
+%	O
+of	O
+all	O
+CVDs	O
+and	O
+are	O
+a	O
+growing	O
+clinical	O
+challenge	O
+in	O
+need	O
+of	O
+novel	O
+therapeutic	O
+strategies	O
+.	O
+
+In	O
+this	O
+study	O
+,	O
+we	O
+investigated	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+as	O
+a	O
+potential	O
+new	O
+therapeutic	O
+target	O
+for	O
+reduction	O
+of	O
+cardiac	O
+apoptosis	O
+and	O
+cardiac	O
+injury	O
+in	O
+these	O
+conditions	O
+.	O
+
+Using	O
+ribozyme	O
+technology	O
+we	O
+down	O
+-	O
+regulated	O
+the	O
+expression	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+neonatal	O
+cardiac	O
+myocytes	O
+.	O
+
+We	O
+then	O
+examined	O
+cell	O
+proliferation	O
+and	O
+apoptosis	O
+under	O
+normal	O
+conditions	O
+and	O
+post	O
+challenge	O
+with	O
+either	O
+hypoxia	O
+,	O
+a	O
+model	O
+of	O
+ischemia	O
+-	O
+reperfusion	O
+,	O
+or	O
+TNF	O
+-	O
+alpha	O
+,	O
+a	O
+cytokine	O
+implicated	O
+in	O
+the	O
+pathogenesis	O
+of	O
+chronic	O
+heart	O
+failure	O
+[	O
+19	O
+]	O
+.	O
+
+Our	O
+results	O
+demonstrate	O
+an	O
+association	O
+of	O
+a	O
+decrease	O
+in	O
+the	O
+expression	O
+and	O
+function	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+with	O
+increased	O
+cell	O
+proliferation	O
+and	O
+decreased	O
+cell	O
+susceptibility	O
+to	O
+hypoxia	O
+-	O
+and	O
+TNF	O
+-	O
+induced	O
+apoptosis	O
+.	O
+
+Expression	O
+of	O
+the	O
+ribozyme	O
+targeted	O
+against	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+cardiomyocytes	O
+resulted	O
+in	O
+down	O
+-	O
+regulation	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+,	O
+as	O
+measured	O
+by	O
+RT	O
+-	O
+PCR	O
+and	O
+RPA	O
+,	O
+and	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+function	O
+,	O
+as	O
+indicated	O
+by	O
+a	O
+decrease	O
+in	O
+internalization	O
+of	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+,	O
+and	O
+beta	O
+-	O
+glucuronidase	O
+binding	O
+and	O
+endocytosis	O
+.	O
+
+MTT	O
+analysis	O
+and	O
+viable	O
+cell	O
+counts	O
+showed	O
+that	O
+ribozyme	O
+-	O
+mediated	O
+down	O
+-	O
+regulation	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+resulted	O
+in	O
+a	O
+marked	O
+increase	O
+in	O
+cell	O
+proliferation	O
+of	O
+cardiomyocytes	O
+,	O
+which	O
+normally	O
+express	O
+high	O
+levels	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+[	O
+20	O
+]	O
+and	O
+have	O
+limited	O
+proliferative	O
+capabilities	O
+[	O
+21	O
+]	O
+.	O
+
+These	O
+results	O
+are	O
+consistent	O
+with	O
+the	O
+findings	O
+of	O
+previous	O
+knockout	O
+studies	O
+[	O
+9	O
+,	O
+10	O
+]	O
+.	O
+
+Since	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+has	O
+multiple	O
+actions	O
+on	O
+cell	O
+growth	O
+,	O
+its	O
+proliferative	O
+effect	O
+on	O
+the	O
+heart	O
+cells	O
+observed	O
+in	O
+this	O
+study	O
+might	O
+involve	O
+multiple	O
+mechanisms	O
+.	O
+
+However	O
+,	O
+it	O
+is	O
+likely	O
+that	O
+unchecked	O
+IGF	O
+-	O
+II	O
+stimulation	O
+plays	O
+a	O
+key	O
+role	O
+in	O
+the	O
+effect	O
+.	O
+
+Because	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+is	O
+believed	O
+to	O
+sequester	O
+and	O
+degrade	O
+IGF	O
+-	O
+II	O
+[	O
+2	O
+]	O
+,	O
+a	O
+decrease	O
+in	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+and	O
+function	O
+could	O
+result	O
+in	O
+decreased	O
+degradation	O
+and	O
+hence	O
+increased	O
+bioavailability	O
+of	O
+IGF	O
+-	O
+II	O
+to	O
+the	O
+IGF	O
+-	O
+I	O
+receptor	O
+,	O
+which	O
+mediates	O
+the	O
+growth	O
+-	O
+promoting	O
+effect	O
+of	O
+IGF	O
+-	O
+II	O
+.	O
+
+Supporting	O
+evidence	O
+for	O
+the	O
+involvement	O
+of	O
+IGF	O
+-	O
+II	O
+in	O
+the	O
+proliferative	O
+effect	O
+resulting	O
+from	O
+loss	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+function	O
+comes	O
+from	O
+studies	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+knock	O
+-	O
+out	O
+mice	B
+.	O
+
+M6P	O
+/	O
+IGF2R	O
+-	O
+null	O
+mice	B
+display	O
+global	O
+hyperplasia	O
+that	O
+coincides	O
+with	O
+elevated	O
+levels	O
+of	O
+IGF	O
+-	O
+II	O
+.	O
+
+Most	O
+importantly	O
+,	O
+however	O
+,	O
+the	O
+lethal	O
+nature	O
+of	O
+an	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+null	O
+phenotype	O
+is	O
+reversed	O
+in	O
+an	O
+IGF	O
+-	O
+II	O
+-	O
+null	O
+background	O
+[	O
+9	O
+]	O
+.	O
+
+Our	O
+results	O
+showing	O
+that	O
+ribozyme	O
+-	O
+mediated	O
+down	O
+-	O
+regulation	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+lead	O
+to	O
+a	O
+decrease	O
+in	O
+IGF	O
+-	O
+II	O
+internalization	O
+support	O
+the	O
+above	O
+possibility	O
+.	O
+
+However	O
+,	O
+further	O
+investigation	O
+to	O
+confirm	O
+this	O
+mechanism	O
+is	O
+warranted	O
+.	O
+
+More	O
+importantly	O
+,	O
+our	O
+results	O
+also	O
+showed	O
+that	O
+M6P	O
+/	O
+IGF2R	O
+down	O
+-	O
+regulation	O
+resulted	O
+in	O
+decreased	O
+sensitivity	O
+of	O
+cardiomyocytes	O
+to	O
+hypoxia	O
+-	O
+and	O
+TNF	O
+-	O
+induced	O
+apoptosis	O
+.	O
+
+There	O
+is	O
+evidence	O
+that	O
+lysosomal	O
+enzymes	O
+,	O
+such	O
+as	O
+cathepsins	O
+B	O
+and	O
+D	O
+contribute	O
+to	O
+hypoxia	O
+-	O
+and	O
+TNF	O
+-	O
+induced	O
+apoptosis	O
+in	O
+vitro	O
+[	O
+22	O
+-	O
+25	O
+]	O
+and	O
+in	O
+vivo	O
+[	O
+26	O
+,	O
+27	O
+]	O
+.	O
+
+The	O
+M6P	O
+/	O
+IGF2R	O
+has	O
+been	O
+shown	O
+to	O
+be	O
+involved	O
+in	O
+binding	O
+,	O
+transport	O
+and	O
+activation	O
+of	O
+lysosomal	O
+enzymes	O
+,	O
+including	O
+cathepsins	O
+[	O
+4	O
+,	O
+5	O
+]	O
+.	O
+
+Therefore	O
+,	O
+it	O
+is	O
+possible	O
+that	O
+down	O
+-	O
+regulation	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+results	O
+in	O
+improper	O
+trafficking	O
+and	O
+activation	O
+of	O
+cathepsins	O
+.	O
+
+This	O
+,	O
+in	O
+turn	O
+would	O
+eliminate	O
+the	O
+apoptotic	O
+cascades	O
+triggered	O
+by	O
+these	O
+enzymes	O
+under	O
+hypoxia	O
+and	O
+TNF	O
+stimulation	O
+and	O
+result	O
+in	O
+decreased	O
+sensitivity	O
+of	O
+cardiomyocytes	O
+to	O
+apoptosis	O
+.	O
+
+It	O
+has	O
+also	O
+been	O
+shown	O
+that	O
+TNF	O
+stimulation	O
+involves	O
+the	O
+activation	O
+of	O
+TGF	O
+-	O
+beta	O
+[	O
+28	O
+-	O
+30	O
+]	O
+,	O
+a	O
+ligand	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+that	O
+has	O
+been	O
+implicated	O
+in	O
+the	O
+progression	O
+of	O
+chronic	O
+heart	O
+failure	O
+[	O
+11	O
+,	O
+31	O
+]	O
+.	O
+
+Therefore	O
+,	O
+down	O
+-	O
+regulation	O
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+M6P	O
+/	O
+IGF2R	O
+expression	O
+could	O
+also	O
+lead	O
+to	O
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+decreased	O
+bioavailability	O
+of	O
+activated	O
+TGF	O
+-	O
+beta	O
+,	O
+thereby	O
+decreasing	O
+the	O
+sensitivity	O
+of	O
+cardiomyocytes	O
+to	O
+the	O
+TNF	O
+/	O
+TGF	O
+-	O
+beta	O
+apoptotic	O
+pathway	O
+.	O
+
+The	O
+detailed	O
+mechanism	O
+of	O
+the	O
+observed	O
+effects	O
+is	O
+unknown	O
+and	O
+requires	O
+further	O
+investigation	O
+.	O
+
+Conclusions	O
+
+The	O
+present	O
+study	O
+demonstrates	O
+that	O
+ribozyme	O
+-	O
+mediated	O
+down	O
+-	O
+regulation	O
+of	O
+expression	O
+and	O
+functional	O
+activity	O
+of	O
+the	O
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+/	O
+IGF2R	O
+results	O
+in	O
+a	O
+decrease	O
+in	O
+the	O
+susceptibility	O
+of	O
+cardiac	O
+myocytes	O
+to	O
+apoptotic	O
+stimuli	O
+.	O
+
+These	O
+findings	O
+suggest	O
+that	O
+this	O
+receptor	O
+might	O
+be	O
+involved	O
+in	O
+cardiac	O
+cell	O
+growth	O
+and	O
+apoptosis	O
+.	O
+
+The	O
+ability	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+ribozyme	O
+to	O
+reduce	O
+M6P	O
+/	O
+IGF2R	O
+expression	O
+and	O
+function	O
+in	O
+transfected	O
+cells	O
+verifies	O
+the	O
+utility	O
+of	O
+the	O
+ribozyme	O
+in	O
+studying	O
+the	O
+role	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+in	O
+cardiomyocyte	O
+growth	O
+and	O
+apoptosis	O
+.	O
+
+In	O
+addition	O
+to	O
+its	O
+utility	O
+as	O
+a	O
+research	O
+tool	O
+,	O
+the	O
+ribozyme	O
+,	O
+with	O
+further	O
+exploration	O
+and	O
+development	O
+,	O
+might	O
+have	O
+potential	O
+application	O
+as	O
+a	O
+therapeutic	O
+agent	O
+to	O
+prevent	O
+cell	O
+death	O
+or	O
+promote	O
+mitogenesis	O
+for	O
+certain	O
+clinical	O
+conditions	O
+,	O
+such	O
+as	O
+,	O
+myocardial	O
+infarction	O
+and	O
+chronic	O
+heart	O
+failure	O
+.	O
+
+Methods	O
+
+Construction	O
+of	O
+recombinant	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+RZ	O
+adenoviral	O
+vector	O
+
+The	O
+nucleotide	O
+numbers	O
+of	O
+the	O
+rat	B
+M6P	O
+/	O
+IGF2R	O
+sequence	O
+targeted	O
+by	O
+the	O
+hammerhead	O
+ribozyme	O
+is	O
+1147	O
+-	O
+1160	O
+after	O
+coding	O
+site	O
+(	O
+exon	O
+9	O
+)	O
+.	O
+
+The	O
+structure	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+hammerhead	O
+ribozyme	O
+is	O
+shown	O
+in	O
+Fig	O
+.	O
+
+1	O
+.	O
+
+A	O
+49	O
+bp	O
+M6P	O
+/	O
+IGF2R	O
+ribozyme	O
+oligonucleotide	O
+,	O
+5	O
+'	O
+-	O
+GAATTCCCC	O
+ACACTG	O
+ATGAGCCGCTTCGGCGGCGA	O
+GCGT	O
+-	O
+3	O
+'	O
+and	O
+the	O
+corresponding	O
+reverse	O
+complementary	O
+strand	O
+were	O
+synthesized	O
+.	O
+
+The	O
+fragments	O
+were	O
+subcloned	O
+to	O
+produce	O
+a	O
+plasmid	O
+containing	O
+a	O
+ribozyme	O
+against	O
+M6P	O
+/	O
+IGF2R	O
+.	O
+
+For	O
+construction	O
+of	O
+the	O
+recombinant	O
+adenovirus	O
+containing	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+-	O
+ribozyme	O
+(	O
+pAd	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+)	O
+,	O
+the	O
+segments	O
+containing	O
+the	O
+ribozymes	O
+were	O
+amplified	O
+by	O
+PCR	O
+and	O
+cloned	O
+into	O
+a	O
+pAdTrack	O
+-	O
+CMV	O
+vector	O
+and	O
+then	O
+recombined	O
+homologously	O
+with	O
+an	O
+adenoviral	O
+backbone	O
+pAdEasy	O
+1	O
+vector	O
+to	O
+generate	O
+(	O
+pAd	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+)	O
+,	O
+following	O
+the	O
+protocol	O
+described	O
+by	O
+He	O
+et	O
+al	O
+.	O
+
+[	O
+32	O
+]	O
+.	O
+
+The	O
+pAd	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+carries	O
+both	O
+the	O
+IGF2R	O
+-	O
+Rz	O
+and	O
+GFP	O
+(	O
+as	O
+reporter	O
+)	O
+genes	O
+,	O
+each	O
+under	O
+the	O
+control	O
+of	O
+separate	O
+cytomegalovirus	O
+(	O
+CMV	O
+)	O
+promoters	O
+.	O
+
+Another	O
+viral	O
+vector	O
+,	O
+pAd	O
+-	O
+GFP	O
+,	O
+which	O
+carries	O
+the	O
+GFP	O
+gene	O
+only	O
+under	O
+the	O
+control	O
+of	O
+the	O
+CMV	O
+promoter	O
+,	O
+was	O
+generated	O
+and	O
+used	O
+as	O
+a	O
+control	O
+vector	O
+.	O
+
+The	O
+adenoviral	O
+vector	O
+DNA	O
+were	O
+linerized	O
+with	O
+Pac	O
+I	O
+and	O
+transfected	O
+into	O
+the	O
+replication	O
+-	O
+permissive	O
+293	O
+cells	O
+(	O
+E1A	O
+transcomplementing	O
+cell	O
+line	O
+)	O
+by	O
+using	O
+Lipofectamine	O
+(	O
+Life	O
+Technologies	O
+)	O
+to	O
+produce	O
+E1	O
+-	O
+deleted	O
+,	O
+replication	O
+-	O
+defective	O
+recombinant	O
+adenovirus	O
+as	O
+described	O
+previously	O
+[	O
+33	O
+]	O
+.	O
+
+Large	O
+-	O
+scale	O
+amplification	O
+of	O
+recombinant	O
+adenovirus	O
+in	O
+293	O
+cells	O
+was	O
+followed	O
+by	O
+purification	O
+using	O
+a	O
+discontinuous	O
+CsCl	O
+gradient	O
+.	O
+
+The	O
+constructs	O
+were	O
+confirmed	O
+by	O
+enzymatic	O
+digestion	O
+and	O
+DNA	O
+sequencing	O
+.	O
+
+Transcription	O
+and	O
+cleavage	O
+reaction	O
+of	O
+ribozyme	O
+in	O
+vitro	O
+
+Plasmids	O
+containing	O
+the	O
+ribozyme	O
+or	O
+the	O
+substrate	O
+(	O
+either	O
+45	O
+bp	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+mRNA	O
+or	O
+an	O
+unmatched	O
+sequence	O
+5	O
+'	O
+-	O
+GTGCTGTCTGTATG	O
+-	O
+3	O
+'	O
+)	O
+were	O
+linearized	O
+with	O
+MluI	O
+,	O
+respectively	O
+.	O
+
+All	O
+transcripts	O
+were	O
+generated	O
+with	O
+T7	O
+RNA	O
+polymerase	O
+(	O
+Promega	O
+)	O
+.	O
+
+Substrate	O
+transcripts	O
+were	O
+labeled	O
+by	O
+incorporation	O
+of	O
+[	O
+alpha	O
+-	O
+32P	O
+]	O
+UTP	O
+(	O
+NEN	O
+Life	O
+Science	O
+Products	O
+,	O
+Inc	O
+.	O
+)	O
+.	O
+
+Specific	O
+activity	O
+of	O
+the	O
+[	O
+alpha	O
+-	O
+32P	O
+]	O
+UTP	O
+(	O
+10	O
+mu	O
+Ci	O
+/	O
+mu	O
+l	O
+)	O
+and	O
+the	O
+base	O
+composition	O
+of	O
+each	O
+substrate	O
+molecule	O
+were	O
+used	O
+to	O
+calculate	O
+the	O
+substrate	O
+concentration	O
+.	O
+
+Ribozyme	O
+transcripts	O
+were	O
+quantified	O
+spectrophotometrical	O
+.	O
+
+(	O
+The	O
+half	O
+-	O
+life	O
+of	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+target	O
+is	O
+about	O
+280	O
+minutes	O
+)	O
+.	O
+
+Cleavage	O
+reaction	O
+mixture	O
+contained	O
+substrate	O
+RNA	O
+(	O
+40	O
+nM	O
+)	O
+,	O
+increasing	O
+amounts	O
+of	O
+ribozyme	O
+(	O
+60	O
+nM	O
+)	O
+,	O
+20	O
+mM	O
+MgCl2	O
+and	O
+20	O
+mM	O
+Tris	O
+-	O
+HCl	O
+,	O
+pH8	O
+.	O
+0	O
+,	O
+in	O
+a	O
+final	O
+volume	O
+of	O
+10	O
+mu	O
+l	O
+.	O
+
+The	O
+mixture	O
+was	O
+incubated	O
+at	O
+37	O
+degrees	O
+C	O
+for	O
+a	O
+time	O
+-	O
+course	O
+of	O
+cleavage	O
+reaction	O
+from	O
+0	O
+,	O
+5	O
+,	O
+10	O
+,	O
+20	O
+,	O
+40	O
+,	O
+80	O
+,	O
+160	O
+,	O
+320	O
+,	O
+to	O
+640	O
+minutes	O
+and	O
+the	O
+cleavage	O
+reaction	O
+was	O
+stopped	O
+by	O
+addition	O
+of	O
+loading	O
+buffer	O
+(	O
+80	O
+%	O
+formamide	O
+,	O
+10	O
+mM	O
+Na2EDTA	O
+,	O
+pH	O
+8	O
+.	O
+0	O
+,	O
+and	O
+1	O
+mg	O
+/	O
+ml	O
+each	O
+bromophenol	O
+blue	O
+and	O
+xylene	O
+cyanol	O
+)	O
+.	O
+
+Cleavage	O
+products	O
+were	O
+analyzed	O
+on	O
+a	O
+15	O
+%	O
+polyacrylamide	O
+and	O
+8M	O
+urea	O
+gel	O
+.	O
+
+Product	O
+and	O
+substrate	O
+fragments	O
+were	O
+quantitated	O
+by	O
+using	O
+NIH	O
+Imager	O
+.	O
+
+Cell	O
+cultures	O
+and	O
+infection	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+Rz	O
+-	O
+IGF2R	O
+and	O
+Ad	O
+-	O
+GFP	O
+
+Cardiac	O
+myocytes	O
+were	O
+isolated	O
+from	O
+1	O
+-	O
+day	O
+-	O
+old	O
+newborn	O
+rats	B
+using	O
+the	O
+Neonatal	O
+Cardiomyocyte	O
+Isolation	O
+System	O
+(	O
+Worthington	O
+)	O
+.	O
+
+The	O
+isolated	O
+cells	O
+were	O
+plated	O
+in	O
+6	O
+-	O
+well	O
+plates	O
+and	O
+cultured	O
+in	O
+F	O
+-	O
+10	O
+medium	O
+containing	O
+5	O
+%	O
+(	O
+vol	O
+/	O
+vol	O
+)	O
+FBS	O
+and	O
+10	O
+%	O
+(	O
+vol	O
+/	O
+vol	O
+)	O
+horse	B
+serum	O
+at	O
+37	O
+degrees	O
+C	O
+in	O
+a	O
+tissue	O
+culture	O
+incubator	O
+with	O
+5	O
+%	O
+CO2	O
+and	O
+98	O
+%	O
+relative	O
+humidity	O
+.	O
+
+Cells	O
+were	O
+used	O
+for	O
+experiments	O
+after	O
+2	O
+-	O
+3	O
+days	O
+of	O
+culture	O
+.	O
+
+Viral	O
+infections	O
+were	O
+carried	O
+out	O
+by	O
+adding	O
+viral	O
+particles	O
+at	O
+various	O
+concentrations	O
+(	O
+usually	O
+,	O
+2	O
+x	O
+108	O
+virus	O
+particles	O
+/	O
+ml	O
+)	O
+to	O
+culture	O
+medium	O
+containing	O
+2	O
+%	O
+(	O
+vol	O
+/	O
+vol	O
+)	O
+FBS	O
+.	O
+
+Initially	O
+,	O
+optimal	O
+viral	O
+concentration	O
+was	O
+determined	O
+by	O
+using	O
+Ad	O
+-	O
+GFP	O
+to	O
+achieve	O
+an	O
+optimal	O
+balance	O
+of	O
+high	O
+gene	O
+expression	O
+and	O
+low	O
+viral	O
+titer	O
+to	O
+minimize	O
+cytotoxicity	O
+.	O
+
+After	O
+24	O
+hours	O
+of	O
+incubation	O
+,	O
+the	O
+infection	O
+medium	O
+was	O
+replaced	O
+with	O
+normal	O
+(	O
+15	O
+%	O
+vol	O
+/	O
+vol	O
+serum	O
+)	O
+culture	O
+medium	O
+.	O
+
+For	O
+treatment	O
+with	O
+IGF	O
+-	O
+II	O
+,	O
+cells	O
+were	O
+incubated	O
+with	O
+50	O
+ng	O
+/	O
+ml	O
+IGF	O
+-	O
+II	O
+after	O
+24	O
+hours	O
+infection	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+or	O
+Ad	O
+-	O
+GFP	O
+.	O
+
+Four	O
+days	O
+after	O
+infection	O
+,	O
+cells	O
+were	O
+used	O
+for	O
+analysis	O
+of	O
+gene	O
+expression	O
+of	O
+M6P	O
+/	O
+IGF2R	O
+and	O
+its	O
+effect	O
+on	O
+cell	O
+growth	O
+and	O
+apoptosis	O
+.	O
+
+Analysis	O
+of	O
+gene	O
+expression	O
+in	O
+cardiac	O
+myocytes	O
+
+The	O
+M6P	O
+/	O
+IGF2R	O
+transcripts	O
+were	O
+determined	O
+by	O
+both	O
+RT	O
+-	O
+PCR	O
+and	O
+Ribonuclease	O
+Protection	O
+Assay	O
+(	O
+RPA	O
+)	O
+.	O
+
+RT	O
+-	O
+PCR	O
+was	O
+performed	O
+using	O
+the	O
+GeneAmp	O
+EZ	O
+rTth	O
+RNA	O
+PCR	O
+kit	O
+(	O
+Roche	O
+)	O
+.	O
+
+Total	O
+RNA	O
+was	O
+extracted	O
+from	O
+cultured	O
+cells	O
+using	O
+an	O
+RNA	O
+isolation	O
+kit	O
+(	O
+Qiagen	O
+,	O
+)	O
+,	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+M6P	O
+/	O
+IGF2R	O
+transcripts	O
+were	O
+amplified	O
+using	O
+the	O
+primers	O
+(	O
+5	O
+'	O
+-	O
+GACAGGCTCGTTCTGACTTA	O
+-	O
+3	O
+'	O
+)	O
+and	O
+(	O
+5	O
+'	O
+-	O
+CTTCCACTCTTATCCACAGC	O
+-	O
+3	O
+'	O
+)	O
+specific	O
+to	O
+the	O
+M6P	O
+/	O
+IGF2R	O
+.	O
+
+Each	O
+RT	O
+-	O
+PCR	O
+assay	O
+was	O
+performed	O
+in	O
+triplicate	O
+and	O
+product	O
+levels	O
+varied	O
+by	O
+less	O
+than	O
+3	O
+.	O
+2	O
+%	O
+for	O
+each	O
+RNA	O
+sample	O
+.	O
+
+Primers	O
+specific	O
+for	O
+beta	O
+-	O
+actin	O
+cDNA	O
+were	O
+added	O
+to	O
+a	O
+parallel	O
+reaction	O
+to	O
+standardize	O
+for	O
+variations	O
+in	O
+PCR	O
+between	O
+samples	O
+.	O
+
+PCR	O
+products	O
+were	O
+resolved	O
+on	O
+a	O
+1	O
+.	O
+0	O
+%	O
+agarose	O
+gel	O
+,	O
+visualized	O
+under	O
+UV	O
+light	O
+and	O
+quantitated	O
+using	O
+NIH	O
+Imager	O
+.	O
+
+RPA	O
+was	O
+performed	O
+using	O
+the	O
+RPA	O
+III	O
+kit	O
+(	O
+Ambion	O
+,	O
+Austin	O
+,	O
+TX	O
+)	O
+.	O
+
+Briefly	O
+,	O
+total	O
+RNA	O
+was	O
+extracted	O
+from	O
+cultured	O
+cells	O
+using	O
+a	O
+total	O
+RNA	O
+isolation	O
+reagent	O
+(	O
+TRIzol	O
+,	O
+Gibco	O
+BRL	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+The	O
+plasmid	O
+containing	O
+the	O
+rat	B
+M6P	O
+/	O
+IGF2R	O
+gene	O
+was	O
+linearized	O
+and	O
+used	O
+as	O
+a	O
+transcription	O
+template	O
+.	O
+
+Antisense	O
+RNA	O
+probes	O
+were	O
+transcribed	O
+in	O
+vitro	O
+using	O
+[	O
+33P	O
+]	O
+-	O
+UTP	O
+,	O
+T7	O
+polymerase	O
+(	O
+Riboprobea	O
+System	O
+T7	O
+kit	O
+,	O
+Promega	O
+)	O
+,	O
+hybridized	O
+with	O
+the	O
+total	O
+RNA	O
+extracted	O
+from	O
+the	O
+rat	B
+cardiomyocytes	O
+,	O
+and	O
+digested	O
+with	O
+ribonuclease	O
+to	O
+remove	O
+non	O
+-	O
+hybridized	O
+RNA	O
+and	O
+probe	O
+.	O
+
+The	O
+protected	O
+RNA	O
+.	O
+RNA	O
+was	O
+resolved	O
+on	O
+a	O
+denaturing	O
+5	O
+%	O
+sequence	O
+gel	O
+and	O
+subjected	O
+to	O
+autoradiography	O
+.	O
+
+A	O
+probe	O
+targeting	O
+the	O
+GAPDH	O
+gene	O
+was	O
+used	O
+as	O
+an	O
+internal	O
+control	O
+.	O
+
+Measurement	O
+of	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+internalization	O
+
+Cells	O
+were	O
+incubated	O
+at	O
+37	O
+degrees	O
+C	O
+for	O
+2	O
+hrs	O
+in	O
+serum	O
+-	O
+free	O
+F	O
+-	O
+10	O
+culture	O
+medium	O
+containing	O
+125I	O
+-	O
+labeled	O
+IGF	O
+-	O
+II	O
+(	O
+0	O
+.	O
+5	O
+ng	O
+/	O
+ml	O
+)	O
+with	O
+or	O
+without	O
+excess	O
+unlabeled	O
+IGF	O
+-	O
+II	O
+(	O
+2	O
+mu	O
+g	O
+/	O
+ml	O
+)	O
+.	O
+
+Following	O
+the	O
+incubation	O
+,	O
+the	O
+cells	O
+were	O
+washed	O
+three	O
+times	O
+with	O
+ice	O
+-	O
+cold	O
+PBS	O
+,	O
+and	O
+cell	O
+-	O
+associated	O
+radioactivity	O
+was	O
+determined	O
+by	O
+a	O
+gamma	O
+counter	O
+.	O
+
+Specific	O
+internalized	O
+125I	O
+-	O
+IGF	O
+-	O
+II	O
+was	O
+calculated	O
+by	O
+subtracting	O
+the	O
+count	O
+of	O
+samples	O
+with	O
+excessive	O
+unlabeled	O
+IGF	O
+-	O
+II	O
+from	O
+that	O
+without	O
+unlabeled	O
+IGF	O
+-	O
+II	O
+,	O
+and	O
+normalized	O
+to	O
+protein	O
+contents	O
+.	O
+
+Beta	O
+-	O
+glucuronidase	O
+binding	O
+assay	O
+
+Binding	O
+of	O
+beta	O
+-	O
+glucuronidase	O
+was	O
+assayed	O
+as	O
+described	O
+previously	O
+[	O
+34	O
+,	O
+35	O
+]	O
+.	O
+
+Briefly	O
+,	O
+cells	O
+were	O
+permeabilized	O
+with	O
+0	O
+.	O
+25	O
+%	O
+saponin	O
+in	O
+50	O
+mM	O
+Hepes	O
+(	O
+pH	O
+7	O
+.	O
+0	O
+)	O
+,	O
+150	O
+mM	O
+NaCl	O
+,	O
+5	O
+mM	O
+beta	O
+-	O
+glycerophosphate	O
+,	O
+0	O
+.	O
+5	O
+%	O
+human	B
+serum	O
+albumin	O
+,	O
+and	O
+10	O
+mM	O
+mannose	O
+-	O
+6	O
+-	O
+phosphate	O
+(	O
+M6P	O
+)	O
+for	O
+30	O
+minutes	O
+on	O
+ice	O
+.	O
+
+The	O
+cells	O
+were	O
+washed	O
+three	O
+times	O
+with	O
+ice	O
+-	O
+cold	O
+PBS	O
+containing	O
+0	O
+.	O
+05	O
+%	O
+saponin	O
+.	O
+
+They	O
+were	O
+incubated	O
+with	O
+20	O
+,	O
+000	O
+units	O
+/	O
+ml	O
+beta	O
+-	O
+glucuronidase	O
+from	O
+bovine	B
+liver	O
+(	O
+Sigma	O
+)	O
+in	O
+50	O
+mM	O
+Hepes	O
+(	O
+pH	O
+7	O
+.	O
+5	O
+)	O
+containing	O
+150	O
+mM	O
+NaCl	O
+,	O
+5	O
+mM	O
+beta	O
+-	O
+glycerophosphate	O
+,	O
+0	O
+.	O
+5	O
+%	O
+human	B
+serum	O
+albumin	O
+,	O
+0	O
+.	O
+5	O
+%	O
+saponin	O
+with	O
+or	O
+without	O
+10	O
+mM	O
+M6P	O
+overnight	O
+on	O
+ice	O
+.	O
+
+Cells	O
+were	O
+washed	O
+five	O
+times	O
+with	O
+ice	O
+-	O
+cold	O
+PBS	O
+containing	O
+0	O
+.	O
+05	O
+%	O
+saponin	O
+and	O
+sonicated	O
+in	O
+100	O
+mM	O
+sodium	O
+acetate	O
+(	O
+pH	O
+4	O
+.	O
+6	O
+)	O
+.	O
+
+The	O
+protein	O
+concentration	O
+of	O
+solubilized	O
+cell	O
+extract	O
+was	O
+measured	O
+and	O
+enzyme	O
+activity	O
+was	O
+assayed	O
+as	O
+follows	O
+:	O
+for	O
+each	O
+reaction	O
+50	O
+ul	O
+cell	O
+extract	O
+were	O
+added	O
+to	O
+500	O
+ul	O
+of	O
+100	O
+mM	O
+sodium	O
+acetate	O
+(	O
+pH	O
+4	O
+.	O
+0	O
+)	O
+containing	O
+1	O
+mM	O
+paranitrophenyl	O
+(	O
+PNP	O
+)	O
+-	O
+beta	O
+-	O
+glucuronide	O
+(	O
+Sigma	O
+)	O
+as	O
+substrate	O
+.	O
+
+After	O
+an	O
+incubation	O
+period	O
+of	O
+3	O
+hours	O
+at	O
+37	O
+degrees	O
+C	O
+,	O
+500	O
+ul	O
+1	O
+M	O
+Na2CO3	O
+were	O
+added	O
+to	O
+each	O
+reaction	O
+and	O
+the	O
+absorbance	O
+was	O
+measured	O
+at	O
+400	O
+nm	O
+.	O
+
+Experimental	O
+values	O
+were	O
+compared	O
+to	O
+a	O
+standard	O
+curve	O
+that	O
+was	O
+constructed	O
+using	O
+1	O
+-	O
+100	O
+nM	O
+solutions	O
+of	O
+PNP	O
+(	O
+Sigma	O
+)	O
+in	O
+500	O
+ul	O
+100	O
+mM	O
+sodium	O
+acetate	O
+and	O
+500	O
+u1	O
+1	O
+M	O
+Na2CO3	O
+.	O
+
+Specific	O
+activity	O
+was	O
+calculated	O
+as	O
+nM	O
+of	O
+PNP	O
+produced	O
+/	O
+hour	O
+/	O
+mg	O
+of	O
+protein	O
+.	O
+
+Beta	O
+-	O
+glucuronidase	O
+endocytosis	O
+assay	O
+
+Beta	O
+-	O
+glucuronidase	O
+endocytosis	O
+assay	O
+was	O
+carried	O
+out	O
+as	O
+described	O
+previously	O
+[	O
+36	O
+]	O
+.	O
+
+Briefly	O
+,	O
+confluent	O
+cell	O
+cultures	O
+were	O
+washed	O
+twice	O
+with	O
+pre	O
+-	O
+warmed	O
+serum	O
+-	O
+free	O
+DMEM	O
+followed	O
+by	O
+incubation	O
+with	O
+DMEM	O
+containing	O
+5	O
+mg	O
+/	O
+ml	O
+human	B
+serum	O
+albumin	O
+and	O
+10	O
+mM	O
+M6P	O
+for	O
+20	O
+minutes	O
+.	O
+
+Following	O
+incubation	O
+cells	O
+were	O
+washed	O
+3	O
+times	O
+with	O
+pre	O
+-	O
+warmed	O
+DMEM	O
+.	O
+
+Cells	O
+were	O
+then	O
+incubated	O
+in	O
+DMEM	O
+containing	O
+5	O
+mg	O
+/	O
+ml	O
+human	B
+serum	O
+albumin	O
+alone	O
+or	O
+4000	O
+units	O
+beta	O
+-	O
+glucuronidase	O
+with	O
+or	O
+without	O
+10	O
+mM	O
+M6P	O
+for	O
+2	O
+hours	O
+at	O
+37	O
+degrees	O
+C	O
+.	O
+
+Following	O
+the	O
+incubation	O
+,	O
+the	O
+cells	O
+were	O
+washed	O
+5	O
+times	O
+with	O
+ice	O
+-	O
+cold	O
+PBS	O
+and	O
+subjected	O
+to	O
+enzyme	O
+activity	O
+assay	O
+as	O
+described	O
+above	O
+.	O
+
+Cell	O
+proliferation	O
+assay	O
+(	O
+MTT	O
+assay	O
+and	O
+cell	O
+counts	O
+)	O
+
+Cardiac	O
+myocytes	O
+were	O
+grown	O
+in	O
+culture	O
+plates	O
+(	O
+tissue	O
+culture	O
+grade	O
+,	O
+12	O
+wells	O
+,	O
+flat	O
+bottom	O
+)	O
+in	O
+a	O
+final	O
+volume	O
+of	O
+1	O
+ml	O
+serum	O
+-	O
+containing	O
+culture	O
+medium	O
+per	O
+well	O
+,	O
+in	O
+a	O
+humidified	O
+atmosphere	O
+(	O
+37	O
+degrees	O
+C	O
+and	O
+5	O
+%	O
+C02	O
+)	O
+for	O
+3	O
+days	O
+.	O
+
+After	O
+infection	O
+with	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+or	O
+Ad	O
+-	O
+GFP	O
+,	O
+cells	O
+were	O
+incubated	O
+with	O
+or	O
+without	O
+50	O
+ng	O
+/	O
+ml	O
+IGF	O
+-	O
+II	O
+for	O
+4	O
+days	O
+.	O
+
+Following	O
+supplementation	O
+with	O
+IGF	O
+-	O
+II	O
+,	O
+100	O
+mu	O
+l	O
+MTT	O
+labeling	O
+reagent	O
+(	O
+Roche	O
+)	O
+were	O
+added	O
+to	O
+each	O
+well	O
+and	O
+cells	O
+were	O
+incubated	O
+for	O
+4	O
+hours	O
+,	O
+followed	O
+by	O
+addition	O
+of	O
+1	O
+ml	O
+solubilization	O
+solution	O
+into	O
+each	O
+well	O
+.	O
+
+The	O
+plate	O
+was	O
+placed	O
+in	O
+an	O
+incubator	O
+at	O
+37	O
+degrees	O
+C	O
+overnight	O
+.	O
+
+Spectrophotometrical	O
+absorbency	O
+of	O
+the	O
+samples	O
+was	O
+measured	O
+using	O
+an	O
+UV	O
+-	O
+visible	O
+Recording	O
+Spectrophotometer	O
+with	O
+wavelength	O
+of	O
+550	O
+-	O
+690	O
+nm	O
+.	O
+
+In	O
+addition	O
+,	O
+the	O
+total	O
+number	O
+of	O
+viable	O
+cells	O
+in	O
+each	O
+treatment	O
+was	O
+counted	O
+by	O
+trypan	O
+blue	O
+exclusion	O
+method	O
+using	O
+a	O
+hemocytometer	O
+.	O
+
+Induction	O
+and	O
+analysis	O
+of	O
+cell	O
+apoptosis	O
+
+Cells	O
+were	O
+infected	O
+with	O
+Ad	O
+-	O
+GFP	O
+or	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+.	O
+
+Seventy	O
+-	O
+two	O
+hours	O
+post	O
+infection	O
+,	O
+cells	O
+were	O
+treated	O
+with	O
+TNF	O
+(	O
+0	O
+.	O
+1	O
+ng	O
+/	O
+ml	O
+)	O
+for	O
+24	O
+hrs	O
+or	O
+subjected	O
+to	O
+hypoxia	O
+.	O
+
+For	O
+induction	O
+of	O
+apoptosis	O
+by	O
+hypoxia	O
+,	O
+cell	O
+culture	O
+medium	O
+was	O
+changed	O
+to	O
+serum	O
+-	O
+free	O
+F	O
+-	O
+10	O
+saturated	O
+with	O
+95	O
+%	O
+N2	O
+/	O
+5	O
+%	O
+CO2	O
+and	O
+cells	O
+were	O
+placed	O
+in	O
+a	O
+37	O
+degrees	O
+C	O
+airtight	O
+box	O
+saturated	O
+with	O
+95	O
+%	O
+N2	O
+/	O
+5	O
+%	O
+CO2	O
+for	O
+24	O
+hrs	O
+.	O
+
+For	O
+normoxic	O
+controls	O
+,	O
+culture	O
+medium	O
+was	O
+changed	O
+to	O
+F	O
+-	O
+10	O
+/	O
+5	O
+%	O
+F	O
+BS	O
+/	O
+10	O
+%	O
+HS	O
+and	O
+cells	O
+were	O
+placed	O
+in	O
+a	O
+37	O
+degrees	O
+C	O
+/	O
+5	O
+%	O
+CO2	O
+incubator	O
+for	O
+24	O
+hrs	O
+before	O
+analysis	O
+.	O
+
+Apoptotic	O
+cells	O
+were	O
+identified	O
+by	O
+Hoechst	O
+staining	O
+using	O
+the	O
+Vybrant	O
+(	O
+TM	O
+)	O
+Apoptosis	O
+Kit	O
+#	O
+5	O
+(	O
+Molecular	O
+Probes	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+In	O
+addition	O
+,	O
+after	O
+infection	O
+with	O
+Ad	O
+-	O
+GFP	O
+or	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+and	O
+challenge	O
+with	O
+either	O
+TNF	O
+or	O
+hypoxia	O
+,	O
+cell	O
+viability	O
+was	O
+assessed	O
+using	O
+the	O
+MTT	O
+assay	O
+Kit	O
+(	O
+Roche	O
+Molecular	O
+Biochemicals	O
+)	O
+and	O
+cell	O
+apoptosis	O
+was	O
+determined	O
+using	O
+the	O
+Cell	O
+Death	O
+Detection	O
+ELISA	O
+Kit	O
+assay	O
+(	O
+Roche	O
+Molecular	O
+Biochemicals	O
+)	O
+according	O
+to	O
+the	O
+manufacturer	O
+'	O
+s	O
+protocol	O
+.	O
+
+Statistical	O
+analysis	O
+
+Students	O
+'	O
+t	O
+-	O
+test	O
+was	O
+used	O
+to	O
+evaluate	O
+the	O
+difference	O
+between	O
+two	O
+values	O
+.	O
+
+Each	O
+experiment	O
+was	O
+repeated	O
+at	O
+least	O
+three	O
+times	O
+.	O
+
+Statistical	O
+significance	O
+was	O
+accepted	O
+at	O
+the	O
+level	O
+of	O
+p	O
+<	O
+0	O
+.	O
+05	O
+.	O
+
+List	O
+of	O
+abbreviations	O
+used	O
+
+Ad	O
+-	O
+GFP	O
+,	O
+adenovirus	O
+carrying	O
+GFP	O
+gene	O
+;	O
+Ad	O
+-	O
+GFP	O
+/	O
+IGF2R	O
+-	O
+Rz	O
+,	O
+adenovirus	O
+carrying	O
+both	O
+the	O
+ribozyme	O
+against	O
+M6P	O
+/	O
+IGF2R	O
+and	O
+the	O
+GFP	O
+gene	O
+;	O
+GFP	O
+,	O
+green	O
+fluorescent	O
+protein	O
+;	O
+IGF	O
+-	O
+II	O
+,	O
+insulin	O
+-	O
+like	O
+growth	O
+factor	O
+II	O
+;	O
+M6P	O
+/	O
+IGF2R	O
+,	O
+mannose	O
+6	O
+-	O
+phosphate	O
+/	O
+insulin	O
+-	O
+like	O
+growth	O
+factor	O
+II	O
+receptor	O
+;	O
+Rz	O
+,	O
+ribozyme	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+ZC	O
+carried	O
+out	O
+construction	O
+of	O
+the	O
+ribozyme	O
+,	O
+production	O
+of	O
+the	O
+viruses	O
+,	O
+cellular	O
+experiments	O
+,	O
+biochemical	O
+assays	O
+and	O
+data	O
+analysis	O
+.	O
+
+YG	O
+carried	O
+out	O
+the	O
+RPA	O
+assay	O
+and	O
+participated	O
+in	O
+the	O
+molecular	O
+biological	O
+studies	O
+.	O
+
+JXK	O
+conceived	O
+of	O
+the	O
+study	O
+,	O
+participated	O
+in	O
+its	O
+design	O
+and	O
+coordination	O
+,	O
+and	O
+drafted	O
+the	O
+manuscript	O
+.	O
+
+SledgeHMMER	O
+:	O
+a	O
+web	O
+server	O
+for	O
+batch	O
+searching	O
+the	O
+Pfam	O
+database	O
+
+Abstract	O
+
+The	O
+SledgeHMMER	O
+web	O
+server	O
+is	O
+intended	O
+for	O
+genome	O
+-	O
+scale	O
+searching	O
+of	O
+the	O
+Pfam	O
+database	O
+without	O
+having	O
+to	O
+install	O
+this	O
+database	O
+and	O
+the	O
+HMMER	O
+software	O
+locally	O
+.	O
+
+The	O
+server	O
+implements	O
+a	O
+parallelized	O
+version	O
+of	O
+hmmpfam	O
+,	O
+the	O
+program	O
+used	O
+for	O
+searching	O
+the	O
+Pfam	O
+HMM	O
+database	O
+.	O
+
+Pfam	O
+search	O
+results	O
+have	O
+been	O
+calculated	O
+for	O
+the	O
+entire	O
+Swiss	O
+-	O
+Prot	O
+and	O
+TrEmbl	O
+database	O
+sequences	O
+(	O
+~	O
+1	O
+.	O
+2	O
+million	O
+)	O
+on	O
+256	O
+processors	O
+of	O
+IA64	O
+-	O
+based	O
+teragrid	O
+machines	O
+.	O
+
+The	O
+Pfam	O
+database	O
+can	O
+be	O
+searched	O
+in	O
+local	O
+,	O
+glocal	O
+or	O
+merged	O
+mode	O
+,	O
+using	O
+either	O
+gathering	O
+or	O
+E	O
+-	O
+value	O
+thresholds	O
+.	O
+
+Query	O
+sequences	O
+are	O
+first	O
+matched	O
+against	O
+the	O
+pre	O
+-	O
+calculated	O
+entries	O
+to	O
+retrieve	O
+results	O
+,	O
+and	O
+those	O
+without	O
+matches	O
+are	O
+processed	O
+through	O
+a	O
+new	O
+search	O
+process	O
+.	O
+
+Results	O
+are	O
+emailed	O
+in	O
+a	O
+space	O
+-	O
+delimited	O
+tabular	O
+format	O
+upon	O
+completion	O
+of	O
+the	O
+search	O
+.	O
+
+While	O
+most	O
+other	O
+Pfam	O
+-	O
+searching	O
+web	O
+servers	O
+set	O
+a	O
+limit	O
+of	O
+one	O
+sequence	O
+per	O
+query	O
+,	O
+this	O
+server	O
+processes	O
+batch	O
+sequences	O
+with	O
+no	O
+limit	O
+on	O
+the	O
+number	O
+of	O
+input	O
+sequences	O
+.	O
+
+The	O
+web	O
+server	O
+and	O
+downloadable	O
+data	O
+are	O
+accessible	O
+from	O
+http	O
+:	O
+/	O
+/	O
+SledgeHmmer	O
+.	O
+sdsc	O
+.	O
+edu	O
+.	O
+
+INTRODUCTION	O
+
+Searching	O
+for	O
+conserved	O
+domains	O
+has	O
+become	O
+an	O
+integral	O
+part	O
+of	O
+several	O
+bioinformatics	O
+data	O
+analysis	O
+pipelines	O
+.	O
+
+The	O
+Pfam	O
+protein	O
+families	O
+database	O
+[	O
+(	O
+1	O
+)	O
+;	O
+http	O
+:	O
+/	O
+/	O
+pfam	O
+.	O
+wustl	O
+.	O
+edu	O
+]	O
+contains	O
+the	O
+single	O
+largest	O
+public	O
+collection	O
+of	O
+conserved	O
+functional	O
+domains	O
+and	O
+hence	O
+is	O
+integrated	O
+into	O
+many	O
+bioinformatics	O
+resources	O
+.	O
+
+The	O
+current	O
+version	O
+(	O
+release	O
+12	O
+)	O
+of	O
+the	O
+Pfam	O
+-	O
+A	O
+database	O
+contains	O
+7316	O
+HMM	O
+domains	O
+,	O
+making	O
+it	O
+an	O
+indispensable	O
+resource	O
+for	O
+protein	O
+functional	O
+annotation	O
+(	O
+2	O
+)	O
+.	O
+
+However	O
+,	O
+the	O
+size	O
+of	O
+the	O
+Pfam	O
+database	O
+is	O
+quite	O
+large	O
+(	O
+~	O
+600	O
+MB	O
+)	O
+and	O
+genome	O
+-	O
+scale	O
+searching	O
+of	O
+protein	O
+sequences	O
+against	O
+this	O
+database	O
+is	O
+a	O
+highly	O
+compute	O
+-	O
+intensive	O
+task	O
+.	O
+
+Hence	O
+,	O
+with	O
+the	O
+exception	O
+of	O
+the	O
+Sanger	O
+Center	O
+web	O
+server	O
+(	O
+http	O
+:	O
+/	O
+/	O
+www	O
+.	O
+sanger	O
+.	O
+ac	O
+.	O
+uk	O
+/	O
+Software	O
+/	O
+Pfam	O
+)	O
+,	O
+all	O
+other	O
+Pfam	O
+-	O
+searching	O
+servers	O
+permit	O
+submission	O
+of	O
+only	O
+one	O
+protein	O
+sequence	O
+at	O
+a	O
+time	O
+(	O
+http	O
+:	O
+/	O
+/	O
+pfam	O
+.	O
+wustl	O
+.	O
+edu	O
+,	O
+http	O
+:	O
+/	O
+/	O
+pfam	O
+.	O
+jouy	O
+.	O
+inra	O
+.	O
+fr	O
+,	O
+http	O
+:	O
+/	O
+/	O
+pfam	O
+.	O
+cgb	O
+.	O
+ki	O
+.	O
+se	O
+)	O
+.	O
+
+Currently	O
+,	O
+the	O
+Sanger	O
+Center	O
+web	O
+server	O
+limits	O
+batch	O
+submission	O
+to	O
+1000	O
+sequences	O
+at	O
+a	O
+time	O
+.	O
+
+Other	O
+than	O
+this	O
+,	O
+for	O
+batch	O
+searching	O
+,	O
+users	O
+are	O
+required	O
+to	O
+install	O
+the	O
+Pfam	O
+database	O
+and	O
+the	O
+HMMER	O
+software	O
+[	O
+(	O
+3	O
+)	O
+;	O
+http	O
+:	O
+/	O
+/	O
+hmmer	O
+.	O
+wustl	O
+.	O
+edu	O
+)	O
+locally	O
+.	O
+
+Given	O
+the	O
+size	O
+and	O
+dynamic	O
+nature	O
+of	O
+this	O
+database	O
+(	O
+14	O
+updates	O
+in	O
+the	O
+last	O
+two	O
+years	O
+)	O
+,	O
+it	O
+is	O
+not	O
+convenient	O
+to	O
+maintain	O
+the	O
+latest	O
+versions	O
+of	O
+these	O
+tools	O
+locally	O
+.	O
+
+Moreover	O
+,	O
+the	O
+hmmpfam	O
+program	O
+used	O
+for	O
+searching	O
+the	O
+Pfam	O
+database	O
+is	O
+very	O
+slow	O
+and	O
+memory	O
+intensive	O
+(	O
+on	O
+Solaris	O
+machines	O
+,	O
+the	O
+processing	O
+speed	O
+is	O
+about	O
+10	O
+sequences	O
+per	O
+1	O
+h	O
+of	O
+CPU	O
+time	O
+)	O
+,	O
+making	O
+this	O
+process	O
+a	O
+bottleneck	O
+in	O
+several	O
+data	O
+analysis	O
+pipelines	O
+.	O
+
+Web	O
+servers	O
+that	O
+enable	O
+batch	O
+searching	O
+of	O
+the	O
+Pfam	O
+database	O
+are	O
+extremely	O
+beneficial	O
+to	O
+the	O
+user	O
+community	O
+,	O
+especially	O
+to	O
+those	O
+without	O
+local	O
+access	O
+to	O
+high	O
+-	O
+end	O
+computational	O
+power	O
+,	O
+memory	O
+and	O
+disk	O
+space	O
+.	O
+
+To	O
+this	O
+end	O
+we	O
+have	O
+developed	O
+a	O
+parallelized	O
+version	O
+,	O
+as	O
+well	O
+as	O
+an	O
+optimized	O
+single	O
+-	O
+processor	O
+version	O
+,	O
+of	O
+hmmpfam	O
+from	O
+release	O
+2	O
+.	O
+3	O
+.	O
+2	O
+of	O
+the	O
+HMMER	O
+software	O
+,	O
+as	O
+described	O
+in	O
+the	O
+next	O
+section	O
+.	O
+
+Using	O
+these	O
+programs	O
+,	O
+we	O
+present	O
+the	O
+SledgeHMMER	O
+web	O
+server	O
+(	O
+http	O
+:	O
+/	O
+/	O
+SledgeHmmer	O
+.	O
+sdsc	O
+.	O
+edu	O
+)	O
+,	O
+which	O
+is	O
+capable	O
+of	O
+batch	O
+searching	O
+a	O
+large	O
+number	O
+of	O
+protein	O
+sequences	O
+concurrently	O
+.	O
+
+DESIGN	O
+AND	O
+IMPLEMENTATION	O
+
+The	O
+current	O
+web	O
+service	O
+is	O
+mainly	O
+intended	O
+for	O
+genome	O
+-	O
+scale	O
+searching	O
+of	O
+the	O
+Pfam	O
+-	O
+A	O
+database	O
+.	O
+
+Searches	O
+are	O
+possible	O
+for	O
+different	O
+Pfam	O
+-	O
+searching	O
+modes	O
+such	O
+as	O
+local	O
+,	O
+glocal	O
+and	O
+merged	O
+,	O
+using	O
+either	O
+gathering	O
+or	O
+E	O
+-	O
+value	O
+thresholds	O
+.	O
+
+To	O
+expedite	O
+the	O
+response	O
+time	O
+,	O
+we	O
+developed	O
+a	O
+database	O
+containing	O
+pre	O
+-	O
+calculated	O
+Pfam	O
+search	O
+results	O
+.	O
+
+Query	O
+sequences	O
+are	O
+matched	O
+against	O
+the	O
+pre	O
+-	O
+calculated	O
+entries	O
+using	O
+hexadecimal	O
+hashing	O
+methods	O
+from	O
+the	O
+MD5	O
+Perl	O
+module	O
+,	O
+and	O
+those	O
+without	O
+matches	O
+are	O
+separated	O
+out	O
+.	O
+
+Results	O
+for	O
+matching	O
+sequences	O
+are	O
+retrieved	O
+from	O
+the	O
+pre	O
+-	O
+calculated	O
+database	O
+while	O
+,	O
+for	O
+other	O
+sequences	O
+,	O
+a	O
+new	O
+search	O
+process	O
+is	O
+initiated	O
+using	O
+our	O
+improved	O
+hmmpfam	O
+program	O
+.	O
+
+Results	O
+are	O
+emailed	O
+in	O
+a	O
+space	O
+-	O
+delimited	O
+tabular	O
+format	O
+upon	O
+completion	O
+of	O
+the	O
+search	O
+.	O
+
+Parallelizing	O
+the	O
+hmmpfam	O
+algorithm	O
+
+Computing	O
+batch	O
+searches	O
+against	O
+the	O
+Pfam	O
+database	O
+is	O
+a	O
+two	O
+-	O
+dimensional	O
+(	O
+2D	O
+)	O
+problem	O
+,	O
+i	O
+.	O
+e	O
+.	O
+searching	O
+N	O
+query	O
+sequences	O
+against	O
+M	O
+Pfam	O
+HMMs	O
+.	O
+
+Thus	O
+,	O
+this	O
+problem	O
+can	O
+be	O
+parallelized	O
+across	O
+any	O
+dimension	O
+or	O
+across	O
+both	O
+dimensions	O
+.	O
+
+A	O
+minor	O
+disadvantage	O
+of	O
+parallelizing	O
+across	O
+the	O
+M	O
+dimension	O
+is	O
+that	O
+a	O
+global	O
+gather	O
+needs	O
+to	O
+be	O
+performed	O
+at	O
+the	O
+end	O
+of	O
+the	O
+computation	O
+to	O
+identify	O
+the	O
+best	O
+matched	O
+HMM	O
+models	O
+.	O
+
+Along	O
+the	O
+N	O
+dimension	O
+the	O
+computation	O
+is	O
+completely	O
+independent	O
+,	O
+however	O
+;	O
+due	O
+to	O
+the	O
+variation	O
+in	O
+the	O
+query	O
+sequence	O
+lengths	O
+,	O
+the	O
+traditional	O
+message	O
+passing	O
+interface	O
+(	O
+MPI	O
+)	O
+technique	O
+of	O
+splitting	O
+the	O
+file	O
+into	O
+equal	O
+numbers	O
+of	O
+sequences	O
+may	O
+result	O
+in	O
+load	O
+imbalance	O
+.	O
+
+Hence	O
+,	O
+the	O
+best	O
+way	O
+to	O
+parallelize	O
+code	O
+along	O
+the	O
+N	O
+dimension	O
+is	O
+to	O
+stripmine	O
+the	O
+query	O
+sequences	O
+as	O
+the	O
+processors	O
+finish	O
+working	O
+on	O
+their	O
+previous	O
+ones	O
+.	O
+
+This	O
+can	O
+be	O
+achieved	O
+using	O
+an	O
+MPI	O
+technique	O
+in	O
+which	O
+one	O
+processor	O
+reads	O
+the	O
+query	O
+sequence	O
+file	O
+and	O
+sends	O
+the	O
+sequences	O
+to	O
+all	O
+others	O
+.	O
+
+Here	O
+,	O
+we	O
+have	O
+parallelized	O
+the	O
+HMMER	O
+code	O
+along	O
+the	O
+N	O
+dimension	O
+(	O
+query	O
+sequences	O
+)	O
+using	O
+a	O
+Unix	O
+-	O
+based	O
+file	O
+-	O
+locking	O
+technique	O
+.	O
+
+This	O
+implementation	O
+requires	O
+all	O
+the	O
+processors	O
+,	O
+nodes	O
+and	O
+computers	O
+working	O
+on	O
+a	O
+single	O
+problem	O
+to	O
+have	O
+access	O
+to	O
+a	O
+file	O
+system	O
+that	O
+honors	O
+Unix	O
+file	O
+locking	O
+.	O
+
+So	O
+far	O
+,	O
+we	O
+have	O
+tested	O
+the	O
+implementation	O
+on	O
+AIX	O
+,	O
+Linux	O
+,	O
+NFS	O
+and	O
+GPFS	O
+file	O
+systems	O
+and	O
+found	O
+our	O
+program	O
+to	O
+work	O
+correctly	O
+.	O
+
+The	O
+advantages	O
+of	O
+parallelizing	O
+with	O
+file	O
+locking	O
+are	O
+that	O
+(	O
+i	O
+)	O
+new	O
+processes	O
+can	O
+join	O
+or	O
+leave	O
+the	O
+process	O
+pool	O
+in	O
+the	O
+middle	O
+of	O
+computing	O
+;	O
+(	O
+ii	O
+)	O
+almost	O
+perfect	O
+load	O
+balancing	O
+can	O
+be	O
+achieved	O
+;	O
+(	O
+iii	O
+)	O
+processors	O
+with	O
+different	O
+clock	O
+speeds	O
+running	O
+different	O
+operating	O
+systems	O
+can	O
+be	O
+part	O
+of	O
+the	O
+same	O
+pool	O
+;	O
+and	O
+(	O
+iv	O
+)	O
+systems	O
+do	O
+not	O
+need	O
+to	O
+have	O
+MPI	O
+or	O
+parallel	O
+virtual	O
+machine	O
+(	O
+PVM	O
+)	O
+installed	O
+.	O
+
+Since	O
+the	O
+parallelized	O
+subroutines	O
+are	O
+written	O
+in	O
+a	O
+separate	O
+file	O
+as	O
+function	O
+calls	O
+,	O
+very	O
+little	O
+change	O
+is	O
+needed	O
+to	O
+the	O
+original	O
+HMMER	O
+code	O
+.	O
+
+These	O
+parallel	O
+routines	O
+are	O
+generic	O
+and	O
+,	O
+hence	O
+,	O
+can	O
+be	O
+used	O
+to	O
+parallelize	O
+other	O
+programs	O
+with	O
+similar	O
+computational	O
+requirements	O
+,	O
+such	O
+as	O
+the	O
+BLAST	O
+suite	O
+of	O
+programs	O
+.	O
+
+A	O
+brief	O
+description	O
+of	O
+the	O
+parallel	O
+function	O
+calls	O
+is	O
+provided	O
+below	O
+.	O
+
+All	O
+the	O
+processes	O
+joining	O
+the	O
+work	O
+pool	O
+will	O
+call	O
+
+The	O
+first	O
+process	O
+that	O
+calls	O
+this	O
+subroutine	O
+will	O
+create	O
+the	O
+lockFile	O
+and	O
+write	O
+the	O
+starting	O
+index	O
+.	O
+
+This	O
+is	O
+the	O
+index	O
+from	O
+which	O
+sequence	O
+stripmining	O
+happens	O
+.	O
+
+The	O
+rest	O
+of	O
+the	O
+processes	O
+open	O
+the	O
+file	O
+stream	O
+to	O
+the	O
+lockFile	O
+.	O
+
+Then	O
+,	O
+inside	O
+the	O
+main	O
+work	O
+loop	O
+,	O
+every	O
+process	O
+calls	O
+
+resulting	O
+in	O
+every	O
+process	O
+getting	O
+a	O
+unique	O
+next	O
+available	O
+job	O
+(	O
+index	O
+)	O
+.	O
+
+Each	O
+process	O
+computes	O
+the	O
+homology	O
+search	O
+for	O
+the	O
+sequence	O
+index	O
+matching	O
+the	O
+unique	O
+index	O
+obtained	O
+.	O
+
+These	O
+steps	O
+are	O
+iterated	O
+until	O
+no	O
+more	O
+sequences	O
+are	O
+left	O
+in	O
+the	O
+query	O
+sequence	O
+file	O
+.	O
+
+Outside	O
+the	O
+work	O
+loop	O
+at	O
+the	O
+end	O
+,	O
+all	O
+the	O
+processes	O
+call	O
+
+which	O
+will	O
+close	O
+the	O
+lockFile	O
+.	O
+
+The	O
+user	O
+has	O
+to	O
+ensure	O
+a	O
+unique	O
+lockFile	O
+for	O
+each	O
+new	O
+query	O
+sequence	O
+file	O
+.	O
+
+If	O
+for	O
+some	O
+reason	O
+the	O
+work	O
+pool	O
+is	O
+stopped	O
+in	O
+the	O
+middle	O
+of	O
+a	O
+query	O
+sequence	O
+file	O
+,	O
+it	O
+can	O
+continue	O
+from	O
+the	O
+same	O
+point	O
+by	O
+using	O
+the	O
+same	O
+lockFile	O
+.	O
+
+In	O
+this	O
+version	O
+of	O
+the	O
+hmmpfam	O
+program	O
+,	O
+all	O
+processes	O
+write	O
+search	O
+results	O
+to	O
+a	O
+single	O
+output	O
+file	O
+.	O
+
+To	O
+minimize	O
+synchronization	O
+overheads	O
+,	O
+each	O
+process	O
+writes	O
+the	O
+output	O
+into	O
+a	O
+temporary	O
+buffer	O
+and	O
+writes	O
+once	O
+per	O
+sequence	O
+into	O
+the	O
+output	O
+file	O
+.	O
+
+For	O
+the	O
+sake	O
+of	O
+convenience	O
+,	O
+additional	O
+synchronization	O
+routines	O
+are	O
+provided	O
+for	O
+locking	O
+and	O
+unlocking	O
+.	O
+
+This	O
+parallel	O
+algorithm	O
+has	O
+been	O
+tested	O
+on	O
+several	O
+platforms	O
+and	O
+file	O
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+including	O
+Intel	O
+IA32	O
+,	O
+IA64	O
+Linux	O
+platforms	O
+,	O
+power3	O
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+-	O
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+-	O
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+.	O
+
+The	O
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+-	O
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+-	O
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+Diego	O
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+(	O
+SDSC	O
+)	O
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+test	O
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+issues	O
+.	O
+
+Single	O
+-	O
+processor	O
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+of	O
+hmmpfam	O
+
+Initially	O
+,	O
+we	O
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+version	O
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+.	O
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+.	O
+
+Performance	O
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+revealed	O
+that	O
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+main	O
+computational	O
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+accessing	O
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+arrays	O
+with	O
+a	O
+wrong	O
+stride	O
+.	O
+
+Correcting	O
+this	O
+resulted	O
+in	O
+doubling	O
+of	O
+the	O
+performance	O
+;	O
+however	O
+,	O
+the	O
+HMMER	O
+developer	O
+has	O
+rectified	O
+this	O
+issue	O
+in	O
+release	O
+2	O
+.	O
+3	O
+.	O
+2	O
+.	O
+
+In	O
+addition	O
+,	O
+HMMER	O
+reads	O
+the	O
+database	O
+file	O
+from	O
+disk	O
+for	O
+every	O
+sequence	O
+it	O
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+.	O
+
+This	O
+is	O
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+for	O
+batch	O
+searches	O
+.	O
+
+We	O
+have	O
+corrected	O
+this	O
+by	O
+reading	O
+the	O
+whole	O
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+into	O
+memory	O
+once	O
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+memory	O
+.	O
+
+Performance	O
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+
+We	O
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+-	O
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+the	O
+equivalent	O
+program	O
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+.	O
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+.	O
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+(	O
+Figure	O
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+)	O
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+
+As	O
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+,	O
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+per	O
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+reduced	O
+up	O
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+10	O
+-	O
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+batch	O
+searches	O
+,	O
+while	O
+in	O
+the	O
+case	O
+of	O
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+.	O
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+.	O
+2	O
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+,	O
+it	O
+is	O
+linear	O
+to	O
+the	O
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+
+Performance	O
+difference	O
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+single	O
+-	O
+sequence	O
+processing	O
+could	O
+be	O
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+differences	O
+.	O
+
+Performance	O
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+the	O
+slope	O
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+plots	O
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+need	O
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+
+Processing	O
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+.	O
+
+Scaling	O
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+were	O
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+-	O
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+
+We	O
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+
+As	O
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+,	O
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+(	O
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+
+This	O
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+
+However	O
+,	O
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+,	O
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+,	O
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+
+Pre	O
+-	O
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+
+We	O
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+-	O
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+for	O
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+entire	O
+Swiss	O
+-	O
+Prot	O
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+TrEmbl	O
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+(	O
+~	O
+1	O
+.	O
+2	O
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+)	O
+,	O
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+our	O
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+-	O
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+.	O
+
+Pfam	O
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+,	O
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+-	O
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+(	O
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+_	O
+ls	O
+)	O
+or	O
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+(	O
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+)	O
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+.	O
+
+Glocal	O
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+all	O
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+search	O
+hits	O
+that	O
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+search	O
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+.	O
+
+Input	O
+and	O
+output	O
+formats	O
+
+The	O
+program	O
+takes	O
+only	O
+FASTA	O
+-	O
+formatted	O
+sequences	O
+as	O
+input	O
+and	O
+searches	O
+can	O
+be	O
+done	O
+in	O
+any	O
+search	O
+mode	O
+,	O
+i	O
+.	O
+e	O
+.	O
+local	O
+,	O
+glocal	O
+or	O
+merged	O
+.	O
+
+The	O
+maximum	O
+E	O
+-	O
+value	O
+allowed	O
+for	O
+searches	O
+is	O
+10	O
+.	O
+
+SledgeHMMER	O
+results	O
+are	O
+emailed	O
+to	O
+the	O
+user	O
+in	O
+a	O
+space	O
+-	O
+delimited	O
+,	O
+one	O
+hit	O
+per	O
+line	O
+tabular	O
+format	O
+(	O
+Figure	O
+2	O
+)	O
+.	O
+
+The	O
+response	O
+time	O
+for	O
+receiving	O
+results	O
+depends	O
+on	O
+the	O
+number	O
+of	O
+query	O
+sequences	O
+and	O
+the	O
+fraction	O
+of	O
+these	O
+existing	O
+in	O
+the	O
+pre	O
+-	O
+calculated	O
+entries	O
+.	O
+
+DISCUSSION	O
+
+The	O
+SledgeHMMER	O
+server	O
+provides	O
+a	O
+unique	O
+service	O
+to	O
+the	O
+scientific	O
+community	O
+wishing	O
+to	O
+batch	O
+search	O
+the	O
+Pfam	O
+database	O
+on	O
+the	O
+web	O
+.	O
+
+To	O
+the	O
+best	O
+of	O
+our	O
+knowledge	O
+,	O
+this	O
+is	O
+the	O
+only	O
+such	O
+server	O
+that	O
+has	O
+no	O
+limit	O
+on	O
+the	O
+number	O
+of	O
+input	O
+sequences	O
+.	O
+
+The	O
+current	O
+pre	O
+-	O
+calculated	O
+database	O
+covers	O
+~	O
+70	O
+%	O
+of	O
+the	O
+available	O
+non	O
+-	O
+redundant	O
+protein	O
+sequence	O
+space	O
+,	O
+and	O
+we	O
+plan	O
+to	O
+add	O
+additional	O
+new	O
+sequences	O
+from	O
+other	O
+resources	O
+such	O
+as	O
+the	O
+NR	O
+database	O
+from	O
+GenBank	O
+and	O
+SEQRES	O
+from	O
+the	O
+PDB	O
+(	O
+Protein	O
+Data	O
+Bank	O
+)	O
+in	O
+the	O
+future	O
+.	O
+
+Our	O
+pre	O
+-	O
+calculated	O
+database	O
+is	O
+updated	O
+for	O
+every	O
+new	O
+release	O
+of	O
+the	O
+Pfam	O
+database	O
+or	O
+SPTr	O
+databases	O
+(	O
+Swiss	O
+-	O
+Prot	O
++	O
+TrEMBL	O
+)	O
+in	O
+order	O
+to	O
+provide	O
+access	O
+to	O
+the	O
+most	O
+current	O
+data	O
+.	O
+
+Single	O
+-	O
+processor	O
+optimized	O
+hmmpfam	O
+binaries	O
+and	O
+the	O
+source	O
+code	O
+can	O
+be	O
+downloaded	O
+from	O
+the	O
+current	O
+web	O
+server	O
+.	O
+
+In	O
+the	O
+future	O
+,	O
+we	O
+intend	O
+to	O
+make	O
+such	O
+binaries	O
+available	O
+for	O
+many	O
+additional	O
+operating	O
+systems	O
+and	O
+propagate	O
+these	O
+modifications	O
+to	O
+other	O
+HMMER	O
+programs	O
+as	O
+well	O
+.	O
+
+Medicinal	O
+herb	O
+use	O
+among	O
+asthmatic	O
+patients	B
+attending	O
+a	O
+specialty	O
+care	O
+facility	O
+in	O
+Trinidad	O
+
+Abstract	O
+
+Background	O
+
+There	O
+is	O
+an	O
+increasing	O
+prevalence	O
+of	O
+asthma	O
+in	O
+the	O
+Caribbean	O
+and	O
+patients	B
+remain	O
+non	O
+-	O
+compliant	O
+to	O
+therapy	O
+despite	O
+the	O
+development	O
+of	O
+guidelines	O
+for	O
+management	O
+and	O
+prevention	O
+.	O
+
+Some	O
+patients	B
+may	O
+self	O
+-	O
+medicate	O
+with	O
+medicinal	O
+herbs	O
+for	O
+symptomatic	O
+relief	O
+,	O
+as	O
+there	O
+is	O
+a	O
+long	O
+tradition	O
+of	O
+use	O
+for	O
+a	O
+variety	O
+of	O
+ailments	O
+.	O
+
+The	O
+study	O
+assessed	O
+the	O
+prevalence	O
+of	O
+use	O
+and	O
+the	O
+factors	O
+affecting	O
+the	O
+decision	O
+to	O
+use	O
+herbs	O
+in	O
+asthmatic	O
+patients	B
+attending	O
+a	O
+public	O
+specialty	O
+care	O
+clinic	O
+in	O
+Trinidad	O
+.	O
+
+Methods	O
+
+A	O
+descriptive	O
+,	O
+cross	O
+-	O
+sectional	O
+study	O
+was	O
+conducted	O
+at	O
+the	O
+Chest	O
+Clinic	O
+in	O
+Trinidad	O
+using	O
+a	O
+de	O
+novo	O
+,	O
+pilot	O
+-	O
+tested	O
+,	O
+researcher	O
+-	O
+administered	O
+questionnaire	O
+between	O
+June	O
+and	O
+July	O
+2003	O
+.	O
+
+Results	O
+
+Fifty	O
+-	O
+eight	O
+out	O
+of	O
+191	O
+patients	B
+(	O
+30	O
+.	O
+4	O
+%	O
+)	O
+reported	O
+using	O
+herbal	O
+remedies	O
+for	O
+symptomatic	O
+relief	O
+.	O
+
+Gender	O
+,	O
+age	O
+,	O
+ethnicity	O
+,	O
+and	O
+asthma	O
+severity	O
+did	O
+not	O
+influence	O
+the	O
+decision	O
+to	O
+use	O
+herbs	O
+;	O
+however	O
+,	O
+62	O
+.	O
+5	O
+%	O
+of	O
+patients	B
+with	O
+tertiary	O
+level	O
+schooling	O
+used	O
+herbs	O
+,	O
+p	O
+=	O
+0	O
+.	O
+025	O
+.	O
+
+Thirty	O
+-	O
+four	O
+of	O
+these	O
+58	O
+patients	B
+(	O
+58	O
+.	O
+6	O
+%	O
+)	O
+obtained	O
+herbs	O
+from	O
+their	O
+backyards	O
+or	O
+the	O
+supermarket	O
+;	O
+only	O
+14	O
+patients	B
+(	O
+24	O
+.	O
+1	O
+%	O
+)	O
+obtained	O
+herbs	O
+from	O
+an	O
+herbalist	O
+,	O
+herbal	O
+shop	O
+or	O
+pharmacy	O
+.	O
+
+Relatives	O
+and	O
+friends	O
+were	O
+the	O
+sole	O
+source	O
+of	O
+information	O
+for	O
+most	O
+patients	B
+(	O
+70	O
+.	O
+7	O
+%	O
+)	O
+,	O
+and	O
+only	O
+10	O
+.	O
+3	O
+%	O
+consulted	O
+an	O
+herbalist	O
+.	O
+
+Ginger	B
+,	O
+garlic	B
+,	O
+aloes	O
+,	O
+shandileer	B
+,	O
+wild	O
+onion	B
+,	O
+pepper	O
+and	O
+black	B
+sage	I
+were	O
+the	O
+most	O
+commonly	O
+used	O
+herbs	O
+.	O
+
+Conclusions	O
+
+Among	O
+patients	B
+attending	O
+the	O
+Chest	O
+Clinic	O
+in	O
+Trinidad	O
+the	O
+use	O
+of	O
+herbal	O
+remedies	O
+in	O
+asthma	O
+is	O
+relatively	O
+common	O
+on	O
+the	O
+advice	O
+of	O
+relatives	O
+and	O
+friends	O
+.	O
+
+It	O
+is	O
+therefore	O
+becoming	O
+imperative	O
+for	O
+healthcare	O
+providers	O
+to	O
+become	O
+more	O
+knowledgeable	O
+on	O
+this	O
+modality	O
+and	O
+to	O
+keep	O
+abreast	O
+with	O
+the	O
+latest	O
+developments	O
+.	O
+
+Background	O
+
+Recent	O
+reports	O
+from	O
+the	O
+Caribbean	O
+suggest	O
+that	O
+the	O
+incidence	O
+of	O
+asthma	O
+is	O
+following	O
+the	O
+global	O
+trend	O
+of	O
+increasing	O
+prevalence	O
+.	O
+
+In	O
+Jamaica	O
+,	O
+a	O
+prevalence	O
+of	O
+20	O
+.	O
+8	O
+%	O
+for	O
+exercise	O
+-	O
+induced	O
+asthma	O
+was	O
+estimated	O
+in	O
+a	O
+cross	O
+-	O
+sectional	O
+study	O
+in	O
+schoolchildren	B
+[	O
+1	O
+]	O
+.	O
+
+About	O
+one	O
+in	O
+ten	O
+patients	B
+attending	O
+an	O
+Accident	O
+and	O
+Emergency	O
+Department	O
+in	O
+Trinidad	O
+were	O
+treated	O
+for	O
+acute	O
+severe	O
+asthma	O
+[	O
+2	O
+]	O
+and	O
+over	O
+15	O
+,	O
+000	O
+patients	B
+attended	O
+four	O
+A	O
+&	O
+E	O
+departments	O
+throughout	O
+the	O
+island	O
+over	O
+a	O
+12	O
+-	O
+month	O
+period	O
+[	O
+3	O
+]	O
+.	O
+
+Inhaled	O
+corticosteroids	O
+as	O
+prophylaxis	O
+and	O
+'	O
+as	O
+required	O
+'	O
+bronchodilator	O
+for	O
+symptomatic	O
+relief	O
+are	O
+established	O
+modalities	O
+for	O
+asthma	O
+management	O
+and	O
+prevention	O
+and	O
+the	O
+Commonwealth	O
+Caribbean	O
+Medical	O
+Research	O
+Council	O
+/	O
+Global	O
+Initiative	O
+for	O
+Asthma	O
+guidelines	O
+were	O
+adopted	O
+in	O
+the	O
+Caribbean	O
+in	O
+1997	O
+[	O
+4	O
+]	O
+.	O
+
+It	O
+has	O
+been	O
+noted	O
+that	O
+inefficient	O
+management	O
+predisposes	O
+patients	B
+to	O
+frequent	O
+hospitalization	O
+and	O
+reduced	O
+quality	O
+of	O
+life	O
+.	O
+
+In	O
+Trinidad	O
+,	O
+non	O
+-	O
+compliance	O
+and	O
+inadequate	O
+inhaler	O
+technique	O
+negatively	O
+impact	O
+on	O
+effective	O
+disease	O
+management	O
+[	O
+5	O
+,	O
+6	O
+]	O
+.	O
+
+The	O
+frequent	O
+unavailability	O
+of	O
+medication	O
+at	O
+public	O
+health	O
+facilities	O
+and	O
+the	O
+prohibitive	O
+cost	O
+at	O
+private	O
+pharmacies	O
+are	O
+significantly	O
+associated	O
+with	O
+non	O
+-	O
+compliance	O
+and	O
+consequently	O
+poor	O
+disease	O
+control	O
+.	O
+
+In	O
+these	O
+studies	O
+,	O
+some	O
+patients	B
+indicated	O
+their	O
+use	O
+of	O
+herbal	O
+remedies	O
+as	O
+an	O
+alternative	O
+to	O
+conventional	O
+medicines	O
+.	O
+
+Over	O
+the	O
+last	O
+few	O
+decades	O
+,	O
+a	O
+global	O
+resurgence	O
+in	O
+the	O
+use	O
+of	O
+herbal	O
+remedies	O
+has	O
+fuelled	O
+the	O
+growing	O
+multi	O
+-	O
+billion	O
+dollar	O
+international	O
+trade	O
+of	O
+botanical	O
+products	O
+.	O
+
+Many	O
+patients	B
+,	O
+dissatisfied	O
+with	O
+conventional	O
+medicines	O
+because	O
+they	O
+expect	O
+permanent	O
+cures	O
+,	O
+believe	O
+that	O
+herbal	O
+remedies	O
+are	O
+'	O
+natural	O
+'	O
+and	O
+sometimes	O
+self	O
+-	O
+medicate	O
+without	O
+informing	O
+their	O
+attending	O
+physician	O
+.	O
+
+Although	O
+there	O
+is	O
+a	O
+long	O
+history	O
+of	O
+traditional	O
+use	O
+of	O
+medicinal	O
+herbs	O
+throughout	O
+the	O
+Caribbean	O
+[	O
+7	O
+,	O
+8	O
+]	O
+few	O
+studies	O
+were	O
+done	O
+to	O
+assess	O
+the	O
+prevalence	O
+of	O
+use	O
+.	O
+
+Surveys	O
+in	O
+Jamaica	O
+reported	O
+an	O
+almost	O
+100	O
+%	O
+use	O
+of	O
+herbal	O
+teas	O
+and	O
+remedies	O
+by	O
+respondents	O
+throughout	O
+the	O
+island	O
+[	O
+9	O
+]	O
+and	O
+71	O
+%	O
+in	O
+paediatrics	O
+inpatients	O
+at	O
+the	O
+University	O
+Hospital	O
+[	O
+10	O
+]	O
+.	O
+
+These	O
+studies	O
+,	O
+however	O
+,	O
+assessed	O
+only	O
+the	O
+lifetime	O
+use	O
+of	O
+medicinal	O
+herbs	O
+and	O
+did	O
+not	O
+identify	O
+their	O
+use	O
+for	O
+any	O
+particular	O
+disease	O
+.	O
+
+In	O
+Trinidad	O
+and	O
+Tobago	O
+,	O
+the	O
+use	O
+of	O
+'	O
+bush	O
+medicine	O
+'	O
+in	O
+diabetic	O
+patients	B
+attending	O
+primary	O
+healthcare	O
+facilities	O
+throughout	O
+the	O
+island	O
+was	O
+assessed	O
+and	O
+although	O
+42	O
+%	O
+reportedly	O
+used	O
+herbs	O
+,	O
+only	O
+24	O
+%	O
+used	O
+this	O
+healthcare	O
+modality	O
+for	O
+self	O
+-	O
+management	O
+of	O
+diabetes	O
+[	O
+11	O
+]	O
+.	O
+
+Another	O
+survey	O
+conducted	O
+at	O
+an	O
+outpatient	O
+surgical	O
+facility	O
+in	O
+Trinidad	O
+indicated	O
+a	O
+lifetime	O
+prevalence	O
+of	O
+86	O
+%	O
+among	O
+patients	B
+[	O
+12	O
+]	O
+for	O
+any	O
+healthcare	O
+issue	O
+.	O
+
+This	O
+study	O
+was	O
+undertaken	O
+to	O
+assess	O
+the	O
+extent	O
+of	O
+use	O
+of	O
+herbal	O
+remedies	O
+by	O
+asthmatic	O
+patients	B
+attending	O
+a	O
+specialty	O
+chest	O
+clinic	O
+in	O
+Trinidad	O
+for	O
+symptomatic	O
+relief	O
+and	O
+to	O
+determine	O
+the	O
+factors	O
+influencing	O
+the	O
+patient	B
+'	O
+s	O
+decision	O
+to	O
+use	O
+herbs	O
+.	O
+
+Methods	O
+
+The	O
+study	O
+was	O
+approved	O
+by	O
+the	O
+Ethics	O
+Committee	O
+of	O
+the	O
+Faculty	O
+of	O
+Medical	O
+Sciences	O
+,	O
+University	O
+of	O
+the	O
+West	O
+Indies	O
+,	O
+St	O
+.	O
+
+Augustine	O
+campus	O
+and	O
+permission	O
+to	O
+interview	O
+patients	B
+was	O
+granted	O
+by	O
+the	O
+Director	O
+of	O
+the	O
+Chest	O
+Clinic	O
+of	O
+the	O
+Ministry	O
+of	O
+Health	O
+,	O
+Trinidad	O
+and	O
+Tobago	O
+.	O
+
+The	O
+study	O
+was	O
+conducted	O
+over	O
+the	O
+two	O
+-	O
+month	O
+period	O
+June	O
+to	O
+July	O
+2003	O
+.	O
+
+Sample	O
+and	O
+setting	O
+
+The	O
+Chest	O
+Clinic	O
+was	O
+chosen	O
+as	O
+the	O
+source	O
+of	O
+subjects	O
+as	O
+this	O
+is	O
+the	O
+only	O
+national	O
+tertiary	O
+level	O
+health	O
+facility	O
+specializing	O
+in	O
+the	O
+management	O
+of	O
+respiratory	O
+diseases	O
+.	O
+
+Patients	B
+entering	O
+the	O
+study	O
+were	O
+physician	O
+-	O
+diagnosed	O
+asthmatics	O
+based	O
+on	O
+self	O
+-	O
+reporting	O
+symptoms	O
+of	O
+wheezing	O
+,	O
+chest	O
+tightness	O
+and	O
+nocturnal	O
+coughing	O
+in	O
+the	O
+previous	O
+year	O
+.	O
+
+Patients	B
+were	O
+recruited	O
+by	O
+consecutive	O
+sampling	O
+and	O
+the	O
+nature	O
+and	O
+purpose	O
+of	O
+the	O
+study	O
+were	O
+explained	O
+on	O
+an	O
+individual	O
+basis	O
+.	O
+
+Those	O
+confirming	O
+their	O
+willingness	O
+to	O
+participate	O
+signed	O
+their	O
+informed	O
+consent	O
+and	O
+were	O
+interviewed	O
+using	O
+a	O
+de	O
+novo	O
+,	O
+pilot	O
+-	O
+tested	O
+,	O
+researcher	O
+-	O
+administered	O
+questionnaire	O
+.	O
+
+Interview	O
+instrument	O
+
+The	O
+questionnaire	O
+assessed	O
+demographic	O
+data	O
+such	O
+as	O
+age	O
+,	O
+gender	O
+,	O
+ethnicity	O
+,	O
+residential	O
+district	O
+,	O
+education	O
+,	O
+employment	O
+and	O
+socioeconomic	O
+status	O
+.	O
+
+Subjects	O
+reported	O
+their	O
+disease	O
+severity	O
+as	O
+intermittent	O
+,	O
+moderate	O
+or	O
+severe	O
+as	O
+determined	O
+by	O
+the	O
+Global	O
+Initiative	O
+for	O
+Asthma	O
+(	O
+GINA	O
+)	O
+guidelines	O
+with	O
+respect	O
+to	O
+symptom	O
+frequency	O
+[	O
+4	O
+]	O
+.	O
+
+Patients	B
+also	O
+reported	O
+their	O
+use	O
+of	O
+herbal	O
+remedies	O
+,	O
+identified	O
+the	O
+herbs	O
+used	O
+,	O
+the	O
+frequency	O
+of	O
+use	O
+,	O
+source	O
+of	O
+herbal	O
+medicines	O
+and	O
+the	O
+reasons	O
+for	O
+the	O
+use	O
+of	O
+herbs	O
+.	O
+
+Statistical	O
+analysis	O
+
+The	O
+sample	O
+size	O
+was	O
+calculated	O
+as	O
+185	O
+patients	B
+assuming	O
+a	O
+prevalence	O
+of	O
+86	O
+%	O
+[	O
+13	O
+]	O
+with	O
+a	O
+confidence	O
+level	O
+of	O
+95	O
+%	O
+.	O
+
+Since	O
+all	O
+variables	O
+were	O
+categorical	O
+,	O
+chi	O
+2	O
+tests	O
+were	O
+performed	O
+to	O
+determine	O
+whether	O
+there	O
+were	O
+statistically	O
+significant	O
+associations	O
+between	O
+the	O
+use	O
+of	O
+herbs	O
+and	O
+these	O
+variables	O
+.	O
+
+The	O
+p	O
+value	O
+was	O
+set	O
+at	O
+<	O
+0	O
+.	O
+05	O
+for	O
+statistical	O
+significance	O
+.	O
+
+The	O
+data	O
+was	O
+analyzed	O
+using	O
+SPSS	O
+for	O
+Windows	O
+(	O
+Version	O
+9	O
+.	O
+0	O
+,	O
+Chicago	O
+,	O
+IL	O
+)	O
+.	O
+
+Results	O
+
+Demography	O
+
+During	O
+the	O
+study	O
+period	O
+one	O
+hundred	O
+and	O
+ninety	O
+one	O
+patients	B
+consented	O
+to	O
+participate	O
+.	O
+
+The	O
+demographic	O
+details	O
+of	O
+the	O
+sample	O
+are	O
+given	O
+in	O
+Table	O
+1	O
+.	O
+
+Patients	B
+between	O
+35	O
+and	O
+64	O
+years	O
+of	O
+age	O
+formed	O
+the	O
+largest	O
+portion	O
+of	O
+the	O
+sample	O
+(	O
+62	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+There	O
+was	O
+a	O
+significant	O
+gender	O
+difference	O
+with	O
+females	O
+outnumbering	O
+males	O
+by	O
+a	O
+2	O
+:	O
+1	O
+ratio	O
+,	O
+p	O
+<	O
+0	O
+.	O
+01	O
+.	O
+
+Most	O
+patients	B
+were	O
+of	O
+Asian	O
+Indian	O
+origin	O
+(	O
+58	O
+.	O
+1	O
+%	O
+)	O
+and	O
+resided	O
+in	O
+suburban	O
+areas	O
+(	O
+60	O
+.	O
+2	O
+%	O
+)	O
+.	O
+
+There	O
+was	O
+a	O
+high	O
+level	O
+of	O
+unemployment	O
+(	O
+30	O
+.	O
+4	O
+%	O
+)	O
+;	O
+this	O
+could	O
+be	O
+correlated	O
+to	O
+primary	O
+schooling	O
+(	O
+seven	O
+or	O
+less	O
+years	O
+of	O
+formal	O
+education	O
+)	O
+being	O
+the	O
+highest	O
+educational	O
+level	O
+attained	O
+in	O
+52	O
+.	O
+9	O
+%	O
+and	O
+no	O
+formal	O
+schooling	O
+in	O
+5	O
+.	O
+2	O
+%	O
+of	O
+the	O
+sample	O
+population	O
+.	O
+
+Income	O
+was	O
+low	O
+,	O
+with	O
+42	O
+.	O
+9	O
+%	O
+of	O
+the	O
+sample	O
+population	O
+earning	O
+below	O
+US	O
+$	O
+4	O
+,	O
+000	O
+per	O
+year	O
+.	O
+
+Antiasthmatic	O
+drug	O
+use	O
+
+The	O
+GINA	O
+guidelines	O
+were	O
+recently	O
+adopted	O
+in	O
+the	O
+Caribbean	O
+and	O
+asthmatic	O
+patients	B
+are	O
+currently	O
+treated	O
+according	O
+to	O
+their	O
+symptom	O
+severity	O
+.	O
+
+In	O
+our	O
+sample	O
+population	O
+,	O
+particularly	O
+in	O
+patients	B
+with	O
+moderate	O
+and	O
+severe	O
+symptoms	O
+,	O
+corticosteroids	O
+(	O
+controllers	O
+)	O
+and	O
+beta	O
+2	O
+-	O
+agonists	O
+(	O
+relievers	O
+)	O
+were	O
+prescribed	O
+at	O
+very	O
+high	O
+rates	O
+,	O
+Table	O
+2	O
+.	O
+
+Almost	O
+90	O
+%	O
+of	O
+all	O
+patients	B
+with	O
+moderate	O
+symptoms	O
+were	O
+prescribed	O
+drugs	O
+in	O
+these	O
+classes	O
+.	O
+
+Almost	O
+all	O
+patients	B
+with	O
+severe	O
+symptoms	O
+were	O
+prescribed	O
+beta	O
+2	O
+-	O
+agonists	O
+.	O
+
+This	O
+high	O
+level	O
+of	O
+prescription	O
+and	O
+use	O
+of	O
+beta	O
+2	O
+-	O
+agonists	O
+suggest	O
+a	O
+lack	O
+of	O
+symptomatic	O
+control	O
+in	O
+our	O
+sample	O
+population	O
+.	O
+
+Theophylline	O
+and	O
+anticholinergics	O
+were	O
+prescribed	O
+in	O
+both	O
+categories	O
+of	O
+patients	B
+,	O
+but	O
+to	O
+a	O
+lesser	O
+extent	O
+.	O
+
+Factors	O
+influencing	O
+the	O
+use	O
+of	O
+herbal	O
+remedies	O
+
+Gender	O
+,	O
+age	O
+,	O
+ethnicity	O
+,	O
+residential	O
+district	O
+,	O
+employment	O
+status	O
+,	O
+income	O
+and	O
+asthma	O
+severity	O
+had	O
+no	O
+statistically	O
+significant	O
+effect	O
+on	O
+the	O
+use	O
+of	O
+herbal	O
+remedies	O
+within	O
+the	O
+sample	O
+population	O
+,	O
+Table	O
+3	O
+.	O
+
+However	O
+,	O
+almost	O
+two	O
+-	O
+thirds	O
+(	O
+62	O
+.	O
+5	O
+%	O
+)	O
+of	O
+patients	B
+with	O
+tertiary	O
+education	O
+used	O
+herbal	O
+remedies	O
+for	O
+asthma	O
+,	O
+p	O
+=	O
+0	O
+.	O
+025	O
+.	O
+
+Characteristics	O
+of	O
+patients	B
+using	O
+herbal	O
+remedies	O
+
+Most	O
+patients	B
+(	O
+70	O
+.	O
+7	O
+%	O
+)	O
+using	O
+herbs	O
+were	O
+advised	O
+by	O
+a	O
+relative	O
+or	O
+friend	O
+and	O
+only	O
+10	O
+.	O
+3	O
+%	O
+sought	O
+the	O
+advice	O
+of	O
+an	O
+herbalist	O
+,	O
+Table	O
+4	O
+.	O
+
+A	O
+cultural	O
+/	O
+traditional	O
+basis	O
+was	O
+the	O
+reason	O
+for	O
+herbal	O
+remedy	O
+usage	O
+in	O
+twenty	O
+-	O
+one	O
+(	O
+36	O
+.	O
+2	O
+%	O
+)	O
+patients	B
+and	O
+another	O
+twelve	O
+(	O
+20	O
+.	O
+7	O
+%	O
+)	O
+patients	B
+used	O
+herbs	O
+because	O
+they	O
+felt	O
+that	O
+were	O
+either	O
+'	O
+natural	O
+'	O
+or	O
+'	O
+healthy	O
+'	O
+.	O
+
+Twelve	O
+(	O
+20	O
+.	O
+7	O
+%	O
+)	O
+patients	B
+used	O
+herbs	O
+because	O
+they	O
+believed	O
+that	O
+their	O
+physician	O
+-	O
+prescribed	O
+allopathic	O
+medicines	O
+were	O
+not	O
+working	O
+.	O
+
+Most	O
+patients	B
+(	O
+58	O
+.	O
+6	O
+%	O
+)	O
+obtained	O
+their	O
+herbs	O
+or	O
+medicinal	O
+plants	O
+from	O
+either	O
+their	O
+backyards	O
+or	O
+the	O
+supermarket	O
+.	O
+
+Only	O
+fourteen	O
+(	O
+24	O
+.	O
+1	O
+%	O
+)	O
+obtained	O
+their	O
+herbal	O
+supplies	O
+from	O
+an	O
+herbalist	O
+,	O
+herbal	O
+shop	O
+or	O
+pharmacy	O
+.	O
+
+Seventeen	O
+(	O
+29	O
+.	O
+3	O
+%	O
+)	O
+of	O
+these	O
+patients	B
+reported	O
+using	O
+herbs	O
+within	O
+the	O
+last	O
+week	O
+and	O
+most	O
+these	O
+patients	B
+(	O
+60	O
+.	O
+3	O
+%	O
+)	O
+used	O
+herbs	O
+within	O
+the	O
+last	O
+six	O
+months	O
+.	O
+
+Many	O
+of	O
+these	O
+patients	B
+were	O
+using	O
+both	O
+physician	O
+-	O
+prescribed	O
+antiasthmatic	O
+drugs	O
+and	O
+herbal	O
+remedies	O
+,	O
+Table	O
+5	O
+.	O
+
+No	O
+patient	B
+with	O
+either	O
+moderate	O
+or	O
+severe	O
+symptoms	O
+indicated	O
+that	O
+herbal	O
+remedies	O
+alone	O
+were	O
+sufficient	O
+to	O
+relieve	O
+symptomatic	O
+episodes	O
+.	O
+
+It	O
+is	O
+interesting	O
+to	O
+note	O
+that	O
+most	O
+patients	B
+with	O
+moderate	O
+symptoms	O
+(	O
+57	O
+.	O
+1	O
+%	O
+)	O
+believed	O
+that	O
+concurrent	O
+use	O
+of	O
+conventional	O
+medications	O
+and	O
+herbs	O
+gave	O
+better	O
+symptomatic	O
+relieve	O
+.	O
+
+One	O
+the	O
+other	O
+hand	O
+,	O
+most	O
+patients	B
+with	O
+severe	O
+symptoms	O
+(	O
+53	O
+.	O
+8	O
+%	O
+)	O
+believed	O
+that	O
+physician	O
+-	O
+prescribed	O
+medications	O
+worked	O
+better	O
+than	O
+herbal	O
+remedies	O
+,	O
+while	O
+23	O
+.	O
+1	O
+%	O
+believed	O
+that	O
+neither	O
+relieved	O
+their	O
+symptoms	O
+.	O
+
+Herbs	O
+used	O
+in	O
+asthma	O
+
+Most	O
+patients	B
+in	O
+the	O
+sample	O
+used	O
+more	O
+than	O
+one	O
+medicinal	O
+herb	O
+simultaneously	O
+,	O
+which	O
+were	O
+usually	O
+prepared	O
+and	O
+administered	O
+as	O
+mixtures	O
+in	O
+teas	O
+.	O
+
+Almost	O
+one	O
+in	O
+four	O
+patients	B
+using	O
+medicinal	O
+herbs	O
+(	O
+22	O
+.	O
+5	O
+%	O
+)	O
+used	O
+either	O
+garlic	B
+(	O
+Allium	B
+sativum	I
+)	O
+or	O
+ginger	B
+(	O
+Zingiber	B
+officinale	I
+)	O
+for	O
+symptomatic	O
+relief	O
+of	O
+asthma	O
+,	O
+Table	O
+6	O
+.	O
+
+Aloes	O
+(	O
+Aloe	B
+vera	I
+)	O
+shandileer	B
+(	O
+Leonotis	B
+nepetifolia	I
+)	O
+,	O
+wild	O
+onion	B
+(	O
+Hymenocallis	B
+tubiflora	I
+)	O
+,	O
+pepper	O
+(	O
+Capsicum	O
+spp	O
+.	O
+)	O
+tulsi	B
+(	O
+Ocimum	B
+gratissimum	I
+)	O
+,	O
+black	B
+sage	I
+(	O
+Cordia	B
+curassavica	I
+)	O
+,	O
+shadon	B
+beni	I
+(	O
+Eryngium	B
+foetidium	I
+)	O
+,	O
+lemongrass	B
+(	O
+Cymbopogon	B
+citratus	I
+)	O
+and	O
+nutmeg	B
+(	O
+Myristica	B
+fragrans	I
+)	O
+were	O
+the	O
+more	O
+popular	O
+traditional	O
+indigenous	O
+West	O
+Indian	O
+medicinal	O
+plants	O
+used	O
+.	O
+
+Two	O
+patients	B
+reported	O
+using	O
+marijuana	O
+(	O
+leaves	O
+and	O
+roots	O
+)	O
+.	O
+
+Herbs	O
+of	O
+European	O
+and	O
+North	O
+American	O
+origin	O
+,	O
+identified	O
+as	O
+Echinacea	O
+(	O
+Echinacea	B
+purpurea	I
+)	O
+,	O
+Golden	B
+Seal	I
+(	O
+Hydrastis	B
+canadensis	I
+)	O
+and	O
+Chamomile	B
+(	O
+Matricaria	B
+chamomilla	I
+)	O
+were	O
+less	O
+frequently	O
+used	O
+.	O
+
+Five	O
+patients	B
+reported	O
+using	O
+trade	O
+name	O
+imported	O
+tablets	O
+for	O
+asthma	O
+.	O
+
+Effect	O
+of	O
+income	O
+and	O
+education	O
+on	O
+the	O
+use	O
+of	O
+herbs	O
+
+Patients	B
+using	O
+easily	O
+accessible	O
+herbs	O
+such	O
+as	O
+ginger	B
+(	O
+Zingiber	B
+officinale	I
+)	O
+and	O
+aloes	O
+(	O
+Aloe	B
+vera	I
+)	O
+,	O
+and	O
+traditional	O
+indigenous	O
+medicinal	O
+herbs	O
+such	O
+as	O
+shandileer	B
+(	O
+Leonotis	B
+nepetifolia	I
+)	O
+and	O
+tulsi	B
+(	O
+Ocimum	B
+gratissimum	I
+)	O
+were	O
+more	O
+likely	O
+to	O
+be	O
+earning	O
+less	O
+than	O
+US	O
+$	O
+12	O
+,	O
+000	O
+,	O
+Table	O
+7	O
+.	O
+
+Herbs	O
+of	O
+European	O
+or	O
+North	O
+American	O
+origin	O
+(	O
+Echinacea	B
+purpurea	I
+and	O
+Matricaria	B
+chamomilla	I
+)	O
+were	O
+more	O
+likely	O
+to	O
+be	O
+used	O
+by	O
+patients	B
+earning	O
+in	O
+excess	O
+of	O
+US	O
+$	O
+12	O
+,	O
+000	O
+per	O
+annum	O
+.	O
+
+Income	O
+did	O
+not	O
+affect	O
+the	O
+use	O
+of	O
+either	O
+garlic	B
+or	O
+cocoa	O
+onion	B
+.	O
+
+Aloes	O
+(	O
+Aloe	B
+vera	I
+)	O
+,	O
+tulsi	B
+(	O
+Ocimum	B
+gratissimum	I
+)	O
+and	O
+golden	O
+seal	O
+were	O
+preferred	O
+in	O
+patients	B
+with	O
+at	O
+least	O
+twelve	O
+years	O
+of	O
+formal	O
+education	O
+,	O
+Table	O
+7	O
+.	O
+
+Garlic	B
+and	O
+Echinacea	B
+were	O
+the	O
+preferred	O
+herbal	O
+medicines	O
+in	O
+patients	B
+with	O
+more	O
+than	O
+twelve	O
+years	O
+formal	O
+education	O
+.	O
+
+Educational	O
+level	O
+did	O
+not	O
+affect	O
+the	O
+patients	B
+'	O
+decision	O
+to	O
+use	O
+shandileer	B
+(	O
+Leonotis	B
+nepetifolia	I
+)	O
+,	O
+wild	O
+onion	B
+(	O
+Hymenocallis	B
+tubiflora	I
+)	O
+or	O
+ginger	B
+(	O
+Zingibe	B
+officinale	I
+)	O
+.	O
+
+Discussion	O
+
+This	O
+is	O
+the	O
+first	O
+study	O
+of	O
+its	O
+kind	O
+in	O
+the	O
+Caribbean	O
+to	O
+assess	O
+the	O
+use	O
+of	O
+medicinal	O
+herbs	O
+by	O
+asthmatic	O
+patients	B
+attending	O
+a	O
+specialty	O
+care	O
+clinic	O
+.	O
+
+The	O
+findings	O
+of	O
+this	O
+study	O
+are	O
+instructive	O
+as	O
+the	O
+use	O
+of	O
+medicinal	O
+herbs	O
+for	O
+self	O
+-	O
+medication	O
+in	O
+disease	O
+management	O
+has	O
+far	O
+reaching	O
+implications	O
+on	O
+the	O
+quality	O
+of	O
+healthcare	O
+delivery	O
+[	O
+14	O
+]	O
+.	O
+
+We	O
+report	O
+a	O
+prevalence	O
+of	O
+30	O
+.	O
+4	O
+%	O
+in	O
+our	O
+patient	B
+sample	O
+,	O
+which	O
+is	O
+significantly	O
+higher	O
+than	O
+that	O
+in	O
+the	O
+UK	O
+,	O
+Denmark	O
+,	O
+Singapore	O
+and	O
+in	O
+the	O
+US	O
+[	O
+15	O
+-	O
+18	O
+]	O
+.	O
+
+Most	O
+patients	B
+using	O
+medicinal	O
+herbs	O
+relied	O
+on	O
+the	O
+advice	O
+of	O
+relatives	O
+and	O
+friends	O
+as	O
+their	O
+sole	O
+source	O
+of	O
+information	O
+,	O
+as	O
+were	O
+caregivers	O
+of	O
+children	O
+in	O
+a	O
+US	O
+study	O
+[	O
+19	O
+]	O
+.	O
+
+We	O
+suggest	O
+that	O
+this	O
+information	O
+on	O
+the	O
+use	O
+of	O
+medicinal	O
+plants	O
+could	O
+have	O
+come	O
+from	O
+traditional	O
+/	O
+cultural	O
+knowledge	O
+,	O
+anecdotal	O
+evidence	O
+or	O
+from	O
+the	O
+greater	O
+public	O
+awareness	O
+through	O
+information	O
+networks	O
+such	O
+as	O
+the	O
+internet	O
+on	O
+the	O
+potential	O
+medicinal	O
+benefits	O
+of	O
+herbs	O
+.	O
+
+Asthma	O
+is	O
+an	O
+emerging	O
+chronic	O
+disease	O
+in	O
+the	O
+Caribbean	O
+and	O
+we	O
+suggest	O
+that	O
+the	O
+traditional	O
+knowledge	O
+in	O
+this	O
+area	O
+may	O
+be	O
+relatively	O
+'	O
+new	O
+'	O
+and	O
+exist	O
+in	O
+relation	O
+to	O
+other	O
+diseases	O
+affecting	O
+the	O
+respiratory	O
+tract	O
+,	O
+such	O
+as	O
+cough	O
+,	O
+the	O
+common	O
+cold	O
+and	O
+the	O
+flu	O
+.	O
+
+This	O
+may	O
+be	O
+one	O
+of	O
+the	O
+reasons	O
+for	O
+the	O
+low	O
+prevalence	O
+of	O
+use	O
+of	O
+herbs	O
+in	O
+elderly	O
+asthmatic	O
+patients	B
+,	O
+as	O
+a	O
+strong	O
+traditional	O
+knowledge	O
+may	O
+not	O
+have	O
+existed	O
+.	O
+
+We	O
+expected	O
+a	O
+higher	O
+prevalence	O
+of	O
+herbal	O
+use	O
+in	O
+individuals	O
+living	O
+in	O
+rural	O
+areas	O
+as	O
+these	O
+districts	O
+are	O
+depots	O
+for	O
+traditional	O
+knowledge	O
+as	O
+was	O
+reported	O
+in	O
+Jamaica	O
+where	O
+rural	O
+respondents	O
+used	O
+a	O
+larger	O
+variety	O
+of	O
+herbs	O
+than	O
+those	O
+living	O
+in	O
+urban	O
+areas	O
+[	O
+10	O
+]	O
+.	O
+
+As	O
+suggested	O
+earlier	O
+,	O
+we	O
+suspect	O
+that	O
+due	O
+to	O
+the	O
+recent	O
+emergence	O
+of	O
+asthma	O
+as	O
+a	O
+chronic	O
+disease	O
+in	O
+the	O
+Caribbean	O
+it	O
+is	O
+reasonable	O
+to	O
+expect	O
+that	O
+traditional	O
+knowledge	O
+in	O
+the	O
+management	O
+of	O
+this	O
+disease	O
+is	O
+not	O
+strong	O
+and	O
+our	O
+results	O
+are	O
+indicative	O
+of	O
+this	O
+.	O
+
+We	O
+suspected	O
+that	O
+employment	O
+status	O
+could	O
+have	O
+predicted	O
+the	O
+use	O
+of	O
+herbs	O
+,	O
+however	O
+,	O
+this	O
+was	O
+not	O
+the	O
+case	O
+in	O
+our	O
+study	O
+sample	O
+.	O
+
+Unemployed	O
+patients	B
+did	O
+not	O
+improvise	O
+more	O
+in	O
+their	O
+use	O
+of	O
+herbal	O
+remedies	O
+than	O
+those	O
+in	O
+other	O
+income	O
+groups	O
+,	O
+even	O
+though	O
+most	O
+of	O
+the	O
+herbs	O
+used	O
+were	O
+relatively	O
+common	O
+,	O
+readily	O
+available	O
+and	O
+cheap	O
+.	O
+
+The	O
+low	O
+socioeconomic	O
+status	O
+of	O
+the	O
+majority	O
+of	O
+the	O
+sample	O
+may	O
+have	O
+prohibited	O
+both	O
+consultation	O
+with	O
+qualified	O
+herbalists	O
+and	O
+the	O
+purchase	O
+of	O
+imported	O
+,	O
+processed	O
+herbs	O
+that	O
+would	O
+have	O
+incurred	O
+additional	O
+out	O
+-	O
+of	O
+-	O
+pocket	O
+expense	O
+to	O
+the	O
+patient	B
+.	O
+
+What	O
+we	O
+noted	O
+was	O
+that	O
+there	O
+was	O
+no	O
+difference	O
+in	O
+the	O
+use	O
+of	O
+herbs	O
+across	O
+the	O
+income	O
+ranges	O
+and	O
+that	O
+in	O
+fact	O
+,	O
+patients	B
+earning	O
+relatively	O
+modest	O
+annual	O
+incomes	O
+between	O
+$	O
+US12	O
+,	O
+000	O
+and	O
+$	O
+US19	O
+,	O
+999	O
+were	O
+most	O
+likely	O
+to	O
+use	O
+herbs	O
+,	O
+although	O
+this	O
+did	O
+not	O
+reach	O
+statistical	O
+significance	O
+.	O
+
+Attaining	O
+a	O
+higher	O
+education	O
+positively	O
+influence	O
+the	O
+decision	O
+to	O
+use	O
+herbs	O
+.	O
+
+We	O
+suggest	O
+that	O
+in	O
+the	O
+absence	O
+of	O
+traditional	O
+knowledge	O
+regarding	O
+the	O
+medicinal	O
+use	O
+of	O
+herbs	O
+for	O
+asthma	O
+,	O
+a	O
+higher	O
+educational	O
+level	O
+may	O
+predispose	O
+an	O
+individual	O
+to	O
+greater	O
+access	O
+to	O
+general	O
+knowledge	O
+,	O
+especially	O
+with	O
+greater	O
+exposure	O
+to	O
+the	O
+internet	O
+and	O
+other	O
+sources	O
+of	O
+information	O
+,	O
+and	O
+this	O
+could	O
+be	O
+a	O
+factor	O
+in	O
+positively	O
+influencing	O
+the	O
+individual	O
+'	O
+s	O
+decision	O
+to	O
+use	O
+medicinal	O
+herbs	O
+.	O
+
+The	O
+availability	O
+of	O
+scientific	O
+evidence	O
+-	O
+based	O
+information	O
+on	O
+the	O
+efficacy	O
+of	O
+herbs	O
+for	O
+diverse	O
+healthcare	O
+problems	O
+may	O
+be	O
+particularly	O
+significant	O
+in	O
+patients	B
+with	O
+the	O
+resources	O
+to	O
+avail	O
+themselves	O
+to	O
+such	O
+information	O
+,	O
+particularly	O
+those	O
+with	O
+higher	O
+educational	O
+and	O
+income	O
+levels	O
+.	O
+
+This	O
+is	O
+particularly	O
+true	O
+for	O
+garlic	B
+and	O
+Echinacea	B
+,	O
+which	O
+have	O
+been	O
+extensively	O
+researched	O
+and	O
+furthermore	O
+patients	B
+with	O
+higher	O
+educational	O
+and	O
+income	O
+levels	O
+would	O
+be	O
+more	O
+likely	O
+be	O
+at	O
+an	O
+advantage	O
+to	O
+access	O
+information	O
+via	O
+literature	O
+or	O
+on	O
+the	O
+world	O
+wide	O
+web	O
+regarding	O
+the	O
+use	O
+of	O
+these	O
+medicinal	O
+plants	O
+.	O
+
+Patients	B
+using	O
+imported	O
+,	O
+processed	O
+,	O
+and	O
+obviously	O
+more	O
+expensive	O
+herbal	O
+medications	O
+were	O
+on	O
+the	O
+higher	O
+end	O
+of	O
+the	O
+socioeconomic	O
+scale	O
+and	O
+were	O
+more	O
+likely	O
+to	O
+afford	O
+these	O
+medications	O
+.	O
+
+It	O
+was	O
+also	O
+observed	O
+that	O
+garlic	B
+and	O
+Echinacea	B
+were	O
+the	O
+herbs	O
+of	O
+choice	O
+in	O
+patients	B
+with	O
+higher	O
+educational	O
+levels	O
+.	O
+
+These	O
+herbs	O
+have	O
+a	O
+long	O
+tradition	O
+of	O
+use	O
+and	O
+are	O
+widely	O
+researched	O
+in	O
+Europe	O
+and	O
+North	O
+America	O
+.	O
+
+The	O
+traditional	O
+use	O
+and	O
+strong	O
+scientific	O
+evidence	O
+to	O
+support	O
+their	O
+therapeutic	O
+efficacy	O
+could	O
+be	O
+important	O
+factors	O
+influencing	O
+the	O
+patient	B
+'	O
+s	O
+decision	O
+.	O
+
+It	O
+has	O
+been	O
+suggested	O
+elsewhere	O
+that	O
+patients	B
+with	O
+higher	O
+educational	O
+levels	O
+also	O
+tend	O
+be	O
+more	O
+involved	O
+in	O
+the	O
+management	O
+of	O
+their	O
+health	O
+;	O
+they	O
+tend	O
+to	O
+self	O
+-	O
+medicate	O
+or	O
+even	O
+suggest	O
+to	O
+their	O
+physicians	O
+the	O
+course	O
+of	O
+therapy	O
+.	O
+
+Although	O
+one	O
+in	O
+five	O
+patients	B
+using	O
+medicinal	O
+herbs	O
+stated	O
+that	O
+"	O
+conventional	O
+medicines	O
+were	O
+not	O
+working	O
+"	O
+as	O
+the	O
+reason	O
+for	O
+using	O
+this	O
+alternative	O
+healthcare	O
+modality	O
+,	O
+we	O
+noted	O
+that	O
+asthma	O
+severity	O
+does	O
+not	O
+affect	O
+the	O
+decision	O
+to	O
+use	O
+herbs	O
+.	O
+
+In	O
+previous	O
+studies	O
+,	O
+poor	O
+management	O
+was	O
+associated	O
+with	O
+non	O
+-	O
+compliance	O
+with	O
+prescribed	O
+pharmacotherapy	O
+and	O
+poor	O
+inhaler	O
+technique	O
+[	O
+5	O
+,	O
+6	O
+]	O
+.	O
+
+The	O
+backyard	O
+and	O
+home	O
+garden	O
+were	O
+major	O
+sources	O
+of	O
+readily	O
+available	O
+herbs	O
+such	O
+as	O
+aloes	O
+,	O
+shadon	B
+beni	I
+and	O
+lemongrass	B
+.	O
+
+Wild	O
+growing	O
+'	O
+weeds	O
+'	O
+such	O
+as	O
+shandileer	B
+,	O
+tulsi	B
+,	O
+cocoa	O
+onion	B
+and	O
+black	B
+sage	I
+were	O
+also	O
+identified	O
+.	O
+
+The	O
+supermarket	O
+was	O
+a	O
+major	O
+source	O
+of	O
+inexpensive	O
+common	O
+medicinal	O
+herbs	O
+such	O
+as	O
+garlic	B
+,	O
+ginger	B
+and	O
+nutmeg	B
+.	O
+
+The	O
+identification	O
+of	O
+these	O
+medicinal	O
+herbs	O
+provides	O
+an	O
+opportunity	O
+to	O
+investigate	O
+West	O
+Indian	O
+plants	O
+used	O
+to	O
+treat	O
+asthma	O
+to	O
+determine	O
+whether	O
+they	O
+possess	O
+pharmacological	O
+properties	O
+.	O
+
+Scientific	O
+investigations	O
+have	O
+shown	O
+that	O
+some	O
+of	O
+these	O
+herbs	O
+possess	O
+pharmacological	O
+and	O
+anti	O
+-	O
+inflammatory	O
+properties	O
+,	O
+and	O
+these	O
+may	O
+be	O
+useful	O
+in	O
+suppressing	O
+the	O
+characteristic	O
+exaggerated	O
+immune	O
+response	O
+in	O
+asthma	O
+[	O
+20	O
+-	O
+24	O
+]	O
+.	O
+
+Pepper	O
+and	O
+bayleaf	B
+have	O
+also	O
+been	O
+shown	O
+to	O
+exhibit	O
+anti	O
+-	O
+inflammatory	O
+properties	O
+[	O
+[	O
+25	O
+,	O
+26	O
+]	O
+27	O
+]	O
+.	O
+
+There	O
+is	O
+an	O
+imperative	O
+to	O
+commence	O
+scientific	O
+investigations	O
+on	O
+traditional	O
+West	O
+Indian	O
+medicinal	O
+plants	O
+to	O
+determine	O
+their	O
+therapeutic	O
+efficacy	O
+and	O
+safety	O
+.	O
+
+The	O
+survey	O
+instrument	O
+specifically	O
+asked	O
+questions	O
+on	O
+the	O
+use	O
+of	O
+medicinal	O
+herbs	O
+in	O
+asthma	O
+and	O
+did	O
+not	O
+inquire	O
+about	O
+the	O
+use	O
+of	O
+herbs	O
+as	O
+customary	O
+teas	O
+or	O
+tonics	O
+.	O
+
+We	O
+therefore	O
+did	O
+not	O
+determine	O
+lifetime	O
+prevalence	O
+for	O
+the	O
+use	O
+of	O
+herbs	O
+in	O
+our	O
+patient	B
+sample	O
+,	O
+but	O
+we	O
+suppose	O
+that	O
+had	O
+this	O
+been	O
+included	O
+that	O
+there	O
+might	O
+have	O
+been	O
+a	O
+prevalence	O
+similar	O
+to	O
+those	O
+reported	O
+in	O
+the	O
+Jamaica	O
+[	O
+10	O
+,	O
+11	O
+]	O
+and	O
+Trinidad	O
+[	O
+13	O
+]	O
+surveys	O
+.	O
+
+The	O
+survey	O
+was	O
+also	O
+limited	O
+in	O
+that	O
+by	O
+electing	O
+to	O
+conduct	O
+the	O
+study	O
+at	O
+a	O
+public	O
+health	O
+facility	O
+we	O
+obviously	O
+had	O
+a	O
+bias	O
+towards	O
+patients	B
+at	O
+the	O
+lower	O
+rung	O
+of	O
+the	O
+socioeconomic	O
+ladder	O
+,	O
+with	O
+lower	O
+income	O
+and	O
+educational	O
+status	O
+.	O
+
+As	O
+a	O
+consequence	O
+,	O
+the	O
+results	O
+reflected	O
+patients	B
+from	O
+this	O
+demographic	O
+background	O
+.	O
+
+We	O
+may	O
+have	O
+expected	O
+a	O
+different	O
+outcome	O
+in	O
+asthmatic	O
+patients	B
+attending	O
+private	O
+institutions	O
+,	O
+where	O
+their	O
+characteristics	O
+would	O
+have	O
+been	O
+slightly	O
+different	O
+,	O
+as	O
+we	O
+noted	O
+that	O
+even	O
+in	O
+our	O
+sample	O
+the	O
+small	O
+number	O
+of	O
+persons	O
+with	O
+higher	O
+income	O
+and	O
+educational	O
+status	O
+tended	O
+to	O
+use	O
+more	O
+medicinal	O
+herbs	O
+for	O
+symptomatic	O
+relief	O
+.	O
+
+We	O
+did	O
+not	O
+assess	O
+whether	O
+patients	B
+informed	O
+their	O
+attending	O
+physician	O
+at	O
+the	O
+clinic	O
+about	O
+their	O
+use	O
+of	O
+herbs	O
+or	O
+determined	O
+whether	O
+the	O
+knowledge	O
+or	O
+attitudes	O
+of	O
+these	O
+physicians	O
+regarding	O
+the	O
+use	O
+of	O
+herbs	O
+influenced	O
+the	O
+patients	B
+'	O
+decision	O
+to	O
+use	O
+herbs	O
+.	O
+
+The	O
+study	O
+was	O
+also	O
+limited	O
+in	O
+that	O
+we	O
+did	O
+not	O
+ascertain	O
+the	O
+out	O
+-	O
+of	O
+-	O
+pocket	O
+expense	O
+for	O
+herbal	O
+remedies	O
+by	O
+patients	B
+,	O
+although	O
+most	O
+stated	O
+that	O
+herbal	O
+medicines	O
+(	O
+which	O
+we	O
+supposed	O
+were	O
+processed	O
+,	O
+imported	O
+products	O
+)	O
+were	O
+more	O
+expensive	O
+than	O
+conventional	O
+medicines	O
+.	O
+
+We	O
+assumed	O
+that	O
+an	O
+additional	O
+expense	O
+would	O
+have	O
+only	O
+been	O
+incurred	O
+by	O
+those	O
+patients	B
+purchasing	O
+processed	O
+,	O
+imported	O
+herbs	O
+obtained	O
+from	O
+a	O
+herbalist	O
+,	O
+herbal	O
+shop	O
+or	O
+pharmacy	O
+(	O
+24	O
+.	O
+1	O
+%	O
+)	O
+and	O
+who	O
+actually	O
+consulted	O
+a	O
+herbalist	O
+(	O
+10	O
+.	O
+3	O
+%	O
+)	O
+.	O
+
+We	O
+also	O
+reasoned	O
+that	O
+since	O
+all	O
+the	O
+other	O
+herbs	O
+used	O
+were	O
+inexpensive	O
+and	O
+available	O
+from	O
+either	O
+the	O
+backyard	O
+garden	O
+or	O
+supermarket	O
+(	O
+58	O
+.	O
+6	O
+%	O
+)	O
+that	O
+the	O
+cost	O
+to	O
+patients	B
+selecting	O
+these	O
+remedies	O
+was	O
+minimal	O
+.	O
+
+Conclusions	O
+
+The	O
+findings	O
+of	O
+this	O
+study	O
+are	O
+important	O
+in	O
+that	O
+local	O
+medicinal	O
+plants	O
+in	O
+Trinidad	O
+have	O
+been	O
+identified	O
+in	O
+the	O
+self	O
+-	O
+management	O
+of	O
+asthma	O
+in	O
+a	O
+significant	O
+number	O
+of	O
+patients	B
+attending	O
+the	O
+specialty	O
+clinic	O
+.	O
+
+These	O
+identified	O
+herbs	O
+can	O
+now	O
+be	O
+targeted	O
+for	O
+scientific	O
+investigation	O
+to	O
+determine	O
+whether	O
+their	O
+pharmacological	O
+efficacy	O
+will	O
+assist	O
+in	O
+the	O
+development	O
+of	O
+viable	O
+healthcare	O
+alternatives	O
+in	O
+a	O
+developing	O
+country	O
+.	O
+
+These	O
+findings	O
+are	O
+also	O
+important	O
+for	O
+policymakers	O
+in	O
+the	O
+health	O
+sector	O
+who	O
+are	O
+given	O
+the	O
+mandate	O
+to	O
+regulate	O
+issues	O
+pertaining	O
+to	O
+the	O
+public	O
+'	O
+s	O
+health	O
+.	O
+
+We	O
+are	O
+also	O
+becoming	O
+more	O
+aware	O
+of	O
+the	O
+potential	O
+for	O
+critical	O
+interplay	O
+between	O
+herbs	O
+and	O
+drugs	O
+when	O
+taken	O
+concomitantly	O
+to	O
+produce	O
+life	O
+-	O
+threatening	O
+interactions	O
+.	O
+
+Since	O
+herbs	O
+are	O
+here	O
+to	O
+stay	O
+and	O
+patients	B
+will	O
+continue	O
+to	O
+self	O
+-	O
+medicate	O
+with	O
+increasing	O
+frequency	O
+,	O
+it	O
+is	O
+imperative	O
+that	O
+healthcare	O
+providers	O
+become	O
+more	O
+knowledgeable	O
+on	O
+this	O
+modality	O
+and	O
+keep	O
+abreast	O
+with	O
+the	O
+latest	O
+developments	O
+in	O
+herbal	O
+therapy	O
+.	O
+
+Competing	O
+interests	O
+
+The	O
+author	O
+(	O
+s	O
+)	O
+declare	O
+that	O
+they	O
+have	O
+no	O
+competing	O
+interests	O
+.	O
+
+Authors	O
+'	O
+contributions	O
+
+YNC	O
+was	O
+the	O
+P	O
+.	O
+I	O
+.	O
+in	O
+this	O
+study	O
+.	O
+
+He	O
+was	O
+responsible	O
+for	O
+the	O
+study	O
+concept	O
+,	O
+development	O
+of	O
+methodology	O
+,	O
+coordinating	O
+the	O
+research	O
+activities	O
+,	O
+analyzing	O
+the	O
+data	O
+,	O
+and	O
+writing	O
+the	O
+manuscript	O
+.	O
+
+AFW	O
+was	O
+responsible	O
+for	O
+data	O
+input	O
+and	O
+analysis	O
+.	O
+
+DA	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+,	O
+data	O
+input	O
+and	O
+analysis	O
+and	O
+presentation	O
+at	O
+regional	O
+conference	O
+.	O
+
+RC	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+,	O
+data	O
+input	O
+and	O
+analysis	O
+.	O
+
+NW	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+and	O
+input	O
+.	O
+
+RM	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+and	O
+input	O
+.	O
+
+OS	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+and	O
+input	O
+.	O
+
+DW	O
+was	O
+involved	O
+in	O
+methodological	O
+development	O
+,	O
+data	O
+collection	O
+and	O
+input	O
+.	O
+
+All	O
+authors	O
+read	O
+and	O
+approved	O
+the	O
+final	O
+manuscript	O
+.	O
+
+Pre	O
+-	O
+publication	O
+history	O
+
+The	O
+pre	O
+-	O
+publication	O
+history	O
+for	O
+this	O
+paper	O
+can	O
+be	O
+accessed	O
+here	O
+:	O
+