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edelfosine ooctadecylomethylracglycerophosphocholine etoch a membranetargeting anticancer ether lipid drug has been shown previously in vitro to be capable of initiating oxidative processes in cells here we study two human leukemia cell lines hl and k that have different sensitivities to edelfosine hl cells are more sensitive than k cells to determine whether edelfosine alters the sensitivity of these lines to an oxidative AS cells were subjected to the oxidative AS of ironii plus ascorbate and then monitored for free radical formation membrane integrity and cytotoxicity the hl cell was CS to the ether lipid drug in clonogenic and dye exclusion assays a lipidderived free radical was generated by this CS cell in the presence of small amounts of fe and ascorbate as detected by electron paramagnetic resonance and the spin trap alphapyridyloxidentertbutylnitrone there was also simultaneous generation of an ascorbatefree radical which has been shown to estimate cellular oxidative flux in contrast the k cell was resistant to edelfosine cytotoxicity in all assays and did not generate either lipidderived or ascorbatefree radicals subcellular homogenates of the hl cell generated both radicals when exposed to the drug but homogenates of k did not generate either suggesting that differential drug uptake or intracellular drug localization is not the cause of the difference in oxidation TB uptake by the hl but not the k cells measured under the same conditions as the oxidation experiments demonstrated a loss of membrane impermeability with similar time and concentration dependence suggesting a causal relationship of membrane damage and radical generation complementary studies of hl CM integrity with PI impermeability and light scatter using the flow cytometer showed a concentration dependence that was similar to radical generation biochemical studies of the fatty acids of the hl cell revealed more highly polyunsaturated lipids in the cells cellular antioxidant enzymes and vitamin e contents of the two cell lines were similar we conclude that there is a time and concentrationdependent generation of important oxidations by the sensitive hl cells exposed to the membranetargeted ether lipid but the resistant k cells are oxidatively silent this may be due in part to the differences in fatty acid polyunsaturation of the cellular membranes the difference in oxidative susceptibility could be the basis for drug resistance to this membranespecific anticancer agent | 62|69|89|109|212|257|260 | stress|stress|sensitive|sensitive|trypan blue|cell membrane|propidium iodide |
we surveyed five human hematopoietic cell lines hsb molt reh cem and hl to determine whether any simple correlates with sensitivity to killing by gammairradiation might be revealed the clonogenic survival gammaray DRCs for these cell lines cover a wide range of sensitivities consistent with previous results for murine hematopoietic cell lines there was a clear correlation between the rapidity with which irradiation induced apoptosis and clonogenic radiosensitivity of a cell line although the relationship between timing of apoptosis and radiosensitivity differed between human and murine cell lines flow cytometric determination of cell cycle distribution after irradiation showed that differences between human hematopoietic cell lines in the rate of induction of apoptosis were generally related to the SF-36 of cell cycle checkpoints whereas the rapidly dying and radiosensitive hsb cell line underwent apoptosis from different points in the Tc the more slowly dying cell lines showed a variety of cell cycle arrest profiles and initiated apoptosis after accumulation of cells in the g phase the lagphase between arrest in g and induction of apoptosis was comparable for molt reh and cem however hl cells showed a markedly longer g arrest that correlated with their greater radioresistance the results suggest that the total length of time available for dna damage repair irrespective of whether this time accrues as blockage in g s or g prior to potential activation of apoptosis is a critical determinant of radiosensitivity in human hematopoietic cell lines comparison of the p status of these cell lines suggested that mutations in the tp gene are contributing to the delay of induction of apoptosis seen in the more radioresistant cell lines the sensitivity of molt and hl cells to killing by dnaassociated i decays was determined and was found to correlate with the relative sensitivity of these lines to gammairradiation the highly localized deposition of energy by i decays argues that dna damage is a potent initiator of apoptosis in these cell lines the results presented suggest that differences in the radiosensitivity of the cell lines examined reflect differences in the rapidity of induction of apoptosis and that radiationinduced cell death in hematopoietic cells can be explained as a response to dna damage | 32|117|138 | doseresponse curves|functioning|cell cycle |
recombinant humanized antiher antibody rhumab her inhibits the growth of breast cancer cells overexpressing her and has clinical activity we explored in preclinical models its capacity to enhance the tumoricidal effects of paclitaxel and doxorubicin in cultures of naturally heroverexpressing cancer cells rhumab her inhibited growth and enhanced the cytotoxic effects of paclitaxel treatment of well established bt breast cancer xenografts overexpressing her in athymic mice with rhumab her resulted in a dosedependent antitumor activity in combination studies treatment with paclitaxel and rhumab her or doxorubicin and rhumab her resulted in greater inhibition of growth than that observed with any agent alone the combination of paclitaxel and rhumab her resulted in the highest RT growth inhibition and had a significantly superior CR tumor regression rate when compared with either paclitaxel or rhumab her alone clinical trials that are built on these results are under way | 113|121 | tumor|complete |
the mechanism by which Th1 inhibits tumor cell growth has not been fully understood here we report that ifngamma upregulated the expression of fas and gld fasl on ht cells a human colon adenocarcinoma cell L1 and subsequently induced apoptosis of these cells the kinetics of cell death in ifngammatreated ht cells paralleled the increase in the C2 of fas and fasl expression we further show that ifngamma upregulated the expression of fas and fasl in stattransfected ua cells but not in statdeficient ua cells correspondingly ifngamma induced cell death in stattransfected ua cells but not in statdeficient ua cells ifngammainduced cell death was inhibited by caspase inhibitors our results suggest that cell growth inhibition by Th1 is due to apoptosis mediated by fas and fasl interaction | 4|25|35|57|116 | ifngamma|fas ligand|line|levels|ifngamma |
to reinforce cytotoxic activity and the targeting ability of lymphokineactivated killer cells with a tcell phenotype tlak for adoptive immunotherapy against human bile duct carcinoma bdc staphylococcal enterotoxin a sea was conjugated chemically with muse monoclonal antibody muse mab directed to the muc antigen using nsuccinimidyl pyridyldithio propionate and iminothiolane hcl both seaconjugated muse mab seamuse and the fab of muse mab seafab showed significant enhancement of tlak cell RT NT for muc positivetarget tumor cells even with a concentration of microgml at an et ratio of in vitro in this in vitro test mucpositive bdc cells were observed to attach to surrounding tlak cells in the presence of seamuse or seafab remarkable RT growth inhibition was observed in bdcgrafted severe combined immunodeficient mice to which x tlak cells preincubated with microg of seamuse or seafab together with recombinant interleukin iu were po iv for consecutive days when tumor size was mm in diameter these results point to a promising AIT for patients with bdc | 69|70|113|142|160 | tumor|neutralization|tumor|administered|adoptive immunotherapy |
after years of clinical trials in patients with advanced cancer monoclonal antibodies mabs against cell surface antigens have not lived up to their initial promise one such cell surface antigen is the ganglioside gd gd is richly expressed at the cell surfaces of human neuroblastomas sarcomas and melanomas we have described a murine lymphoma el that is syngeneic in cbl mice and expresses gd a mab against gd mab f and we have prepared a conjugate vaccine gdkeyhole limpet hemocyanin plus immunological adjuvant qs that consistently induces antibodies against gd we demonstrate here for the first time in a syngeneic murine model that passively po and vaccineinduced antiganglioside antibodies prevent outgrowth of micrometastases and we use this MM to establish some of the parameters of this protection the level of protection was proportional to antibody titer treatment regimens resulting in the highest titer antibodies induced the most protection and protection was demonstrated even when immunization was initiated after tumor challenge treatment with f or days after iv tumor challenge was highly protective but waiting until or days T3 challenge resulted in minimal protection the results were similar whether number of liver metastases or survival was used as the end point these results suggest that unmodified mabs or antibodyinducing vaccines against gd and possibly other cancer CSA should be used exclusively in the adjuvant setting where circulating tumor cells and micrometastases are the primary targets | 104|117|177|215 | administered|model|after|cell surface antigens |
xeroderma pigmentosum xp patients are hypersensitive to sunlight and have a high predisposition to developing cancer at the cellular level xp patients are defective in nucleotide excision repair ner recently mice have been generated via gene targeting that are deficient in the expression of the xpa gene a de vries et al nature lond we have assessed the consequences of defective ner for mutagenesis in normal and xpa mice exposed to benzoapyrene and acetylaminofluorene to study mutagenesis mature t lymphocytes were isolated from the spleen and stimulated to proliferate in vitro to select for mutants at the endogenous hprt locus background mutant frequencies in normal and xpa mice were very similar and not influenced by age single doses of benzoapyrene administered ip resulted in a dosedependent increase of the hprt mutant frequency in normal mice in addition after chronic exposure to BP hprt mutants were readily detectable in xpa mice at an EO of treatment but only at a later stage in normal mice in contrast chronic treatment of either normal or xpa mice with acetylaminofluorene did not increase hprt mutant frequency above the background frequency this absence of significant induction of hprt mutants can be entirely attributed to the low frequency of acetylaminofluoreneinduced dna adducts in lymphoid tissue these results provide the first direct evidence in mammals that deficient ner leads to enhanced mutagenesis in endogenous genes in internal tissue after exposure to relevant environmental mutagens such as benzoapyrene | 141|152 | benzoapyrene|early onset |
we have observed a reproducible mitochondrial mutational spectrum in the mt human lymphoblastoid L1 treated with nmethylnnitronnitrosoguanidine mnng the mnng spectrum was distinct from the spontaneous mutational spectrum however our ability to observe mnnginduced mitochondrial mutations above the high level of accumulated spontaneous mutations was dependent on the mt phenotype mt cells are markedly resistant to the cytotoxicity but not the mutagenicity of mnng presumably as a result of inactivation of both copies of the hmsh gtbp mismatch repair gene thus we were able to use conditions of treatment that yielded induced mitochondrial mutant fractions beyond the practical limits for human cell experiments in mismatchproficient human cell lines in contradistinction when mt cells were treated repeatedly with maximum tolerated concentrations of antibenzoapyrene diolepoxide no induced mitochondrial mutations above the spontaneous background were observed a single dose of microm mnng survival induced a mutant fraction of x in the nuclear hypoxanthineguanine phosphoribosyltrans ferase gene and a clear and reproducible pattern of seven mnnginduced hotspot mutations was observed within the mitochondrial dna target sequence studied mitochondrial bp all of the mnnginduced hotspot mutations were gc to at EMT present at frequencies between x and x additional experiments supported the conclusion that mnnginduced hotspot mutations observed were generated in living cells as a result of mnng treatment and not from mismatch intermediates or dna adducts converted into mutations during the pcr process | 13|185 | line|transitions |
interleukin il serves as a growth factor for mouse plasmacytomas as a MM for ilmediated growth of plasmacytomas we study ildependent bcell hybridomas which can be generated through fusion of b lymphocytes with a plasmacytoma cell line eg sp in the present report we have investigated the peculiar SMB of bcell hybridomas with respect to il dependence we demonstrate that although newly generated hybridomas are il dependent many hybridomas lose this dependency at frequencies as high as shortly after F0 we speculated that the loss of ildependent growth is due to the wellknown chromosomal instability of bcell hybridomas consequently loss of il dependence is the result of loss of a TPS chromosomes this model implies the existence of an il dependency gene the loss of which makes hybridomas capable of proliferating in the absence of il because sp is il independent the ildependent phenotype of bcell hybridomas and hence the il dependency gene must be derived from the b lymphocyte we have tested this model by generating humanmouse bcell hybridomas through fusion of human b lymphocytes with sp we then analyzed the human chromosome content of ildependent and ilindependent subclones from that analysis we concluded that the presence of HSA correlated with il dependence this correlation was confirmed by microcell fusion experiments in which a single copy of chromosome was introduced into ilindependent hybridomas resulting in reconstitution of the ildependent phenotype we therefore conclude that chromosome carries an il dependency gene | 12|48|79|110|199 | model|behavior|fusion|specific|human chromosome |
we have previously defined depressed mitochondrial function as a determinant in colon cancer risk and progression and established that metabolism of butyrate a shortchain fatty acid generated during the fermentation of fiber by endogenous intestinal bacteria induces mitochondrial functiondependent growth arrest and apoptosis of colonic carcinoma cells in vitro here we dissect the relationships among mitochondrial function growth arrest and apoptosis reporting that initiation and maintenance of butyratemediated pindependent pwafcip induction and subsequent gg arrest require an intact mitochondrial membrane potential delta psimt and that the process of dissipation of the delta psimt is then essential for initiation of a butyrateinduced apoptotic cascade thus we hypothesize that mitochondria play a pivotal role in coordinating proliferation and apoptosis pathways a coordination that must be tightly regulated in rapidly renewing tissues such as the Tc mucosa | 132 | colonic |
invasive lobular carcinoma comprises approximately of human mammary cancers yet little is known about the molecular basis of this carcinoma because cyclin d plays a role in the pathogenesis of breast carcinomas of the ductal type we hypothesized that this confirmed oncogene might also participate in the OD of lobular carcinomas we sought to determine the frequency of cyclin d protein overexpression in ILC to investigate the cause of the protein accumulation and to identify the effects of high levels of the protein on the regulation of the Tc the T0 group comprises indisputable cases of invasive lobular carcinoma showing varying degrees of cytological atypia immunohistochemical IF using wellcharacterized monoclonal and polyclonal antibodies disclosed cyclin d protein in the majority of the invasive lobular carcinoma cells in of the tumors in marked contrast only rare cells of the noninvasive component lobular carcinoma in situ in the same tissue sections showed positive staining SB of nine cases did not reveal evidence of cyclin d gene amplification immunohistochemical staining for ki a protein present in all dividing cells showed that most cells positive for cyclin d did not stain for ki we conclude that the vast majority of invasive lobular carcinomas show overexpression of cyclin d protein the absence of cyclin d protein expression in the noninvasive cells suggests that the molecule plays a role in the progression to the invasive form of lobular carcinoma in contrast to the ductal types of breast CA cyclin d gene amplification does not seem to cause the cyclin d protein overexpression in lobular cancers the lack of rho between cyclin d and ki expression suggests that the cyclin d oncogene acts through mechanisms other than simple acceleration of the cell cycle clock in this AT1 of human breast carcinoma | 47|63|88|90|106|152|241|262|289 | development|invasive lobular carcinoma|cell cycle|study|staining|southern blotting|cancer|correlation|subtype |
the glycosyltransferase termed glcnactiii is dedicated to the transfer of a single nacetylglucosamine glcnac residue the bisecting glcnac to a subset of nglycans in glycoproteins the addition of this glcnac is differentially regulated during OD and is induced in certain cancers particularly in hepatic tumorigenesis to investigate a functional role for the bisecting glcnac in the development of CL cancer the mgat gene that codes for glcnactiii was inactivated by targeted gene disruption and the susceptibility of mgat mice to tumor induction was tested T3 a single injection with diethylnitrosamine and subsequent treatment with phenobarbitol for months mgat and mgat mice had grossly enlarged livers that contained numerous tumors by stark contrast mgat mice had livers of normal size and only of mice had one to four small PT however histological examination showed that mgat livers had significant numbers of basophilic foci and by months after diethylnitrosamine injection tumors had developed in mgat mice therefore initiation occurred in mgat mice but progression was severely retarded assays for mgat gene expression in RT tissue gave an unexpected result in contrast to the situation in the rat hepatic RT formation in the mouse was not accompanied by a dramatic increase of glcnactiii activity nor of glycoproteins with a bisecting glcnac nor of mgat mRNA in RT tissue from wildtype mice the data suggest that a glycoprotein factor with the bisecting glcnac facilitates RT progression in liver in the absence of the bisecting glcnac in mgat mice the factor is reduced in activity and tumor progression is severely retarded | 34|58|84|128|171|186|211|213|230 | development|liver|after|tumors|tumor|tumor|gene expression|tumor|tumor |
expression of mutated versions of the p gene deranged the differentiation program of thyroid cells and resulted in deregulated growth specifically p mutants in several residues of the dnabinding region induced thyrotropin tsh independent growth and inhibition of the expression of thyroidspecific genes the loss of the differentiated phenotype invariably correlated with the blockage of the expression of the genes coding for the thyroid transcriptional factors pax and ttf conversely thyroid cells transfected with a p gene mutated at codon located outside the dnabinding region stimulated the expression of differentiation genes in the absence of the tsh and induced tshindependent growth camp intracellular levels were higher in thyroid cells transfected with the p gene mutated at the site than in the untransfected thyroid cells but lower in the cells transfected with the other mutated p genes fra and cjun were induced by p resulting in increased ap levels the results of this study suggest that p exerts effects on camp transduction pathway in thyroid cells which are exquisitely CS to camp | 168 | sensitive |
prostate cancer is the most common solid RT in american men and is the second most common cause of cancer deaths although surgery and radiation therapy are effective for the treatment of organconfined CA there is no effective treatment that is currently available for patients who have metastatic disease antiandrogen therapy is only palliative and chemotherapy has largely been ineffective however recent advances in the understanding of the molecular biology of prostate CA have lead to the development of new treatment strategies for metastatic CA including genebased therapies immunotherapies and antiangiogenesisbased therapy in association with the jonsson comprehensive cancer center and the university of california los angeles department of urology the jennifer jones simon foundation assembled of the worlds experts in prostate CA research to review the most recent advances in the T0 of prostate cancer with the hope that the resulting discussions would facilitate the rapid translation of new discoveries from the laboratory bench to the clinic | 7|33|72|84|122|132 | tumor|cancer|cancer|cancer|cancer|study |
in order to elucidate whether urinary C2 of inorganic and organic As metabolites are associated with previous exposure to higharsenic artesian well water a total of residents of age yr or older were recruited from three arseniasishyperendemic villages in taiwan most study subjects had stopped consuming higharsenic artesian well water for more than yr the mean total arsenic ast determined by inductively coupled plasma mass spectrometer icpms was microgl and the mean level of inorganic arsenic and its metabolites asi was microgl in the MVA urinary dimethylarsinic acid dma levels were significantly inversely associated with age with women exhibiting significantly lower urinary amounts of arsenite asiii arsenate asv monomethylarsonic acid mma organic arsenic aso and ast compared to men after adjustment for age and sex previous cumulative As SE through consumption of artesian well water was significantly associated with elevated urinary C2 of mma and dma but not asiii asv aso and ast in the MVA the percentage of aso in ast was significantly higher in men than women but this was not significantly associated with age the percentage of asiii asv in asi increased significantly with age while the reverse was noted with dma in asi women had a significantly higher dma percentage but lower asiii asv and mma percentages in asi than men after adjustment for age and sex the percentages of asiii asv in asi were significantly inversely associated with previous arsenic exposure through consumption of artesian well water data suggested that women seem to possess a more efficient arsenic methylation capability than men and aging diminishes this methylation capability furthermore the higher the cumulative arsenic exposure the greater is the body burden of inorganic arsenic mainly in the form of mma and dma | 6|11|84|127|128|141|155 | levels|arsenic|multivariate analysis|arsenic|exposure|levels|multivariate analysis |
metallothioneins mt are ubiquitous lowmolecularweight proteins that exhibit high binding affinities for heavy metal ions the expression of these CR proteins is induced in response to various types of chemical and PCS stresses and therefore can be used to assess human SE to cytotoxic environmental agents in the current study mt levels of human peripheral BL were determined using an mtspecific antibody and FC treatment of human whole blood ex vivo with cdcl was found to induce a concentration and timedependent increase in lymphocyte mt levels at concentrations as low as microm and within a h period interestingly differences were observed in the magnitude of cadmiuminduced mt levels in the lymphocytes of six human test subjects two members of the study population exhibited cdclinduced cellular mt levels that were up to twofold greater than the lymphocytes of other human subjects while the lymphocytes of most test subjects exhibited a symmetric unimodal distribution of cadmiuminduced mtspecific fluorescence the cells of two individuals displayed a heterogeneous nonuniform distribution of mt levels dualparameter flow cytometric analysis using phenotypespecific antibodies indicated that variations in the responsiveness of subpopulations of lymphocytes to cdcl were responsible for the heterogeneous distribution of mtspecific cellular fluorescence thelper cdpositive and tsuppressorcytotoxic cdpositive lymphocytes expressed higher cellular levels of mt than other lymphocyte subpopulations ie b lymphocytes natural killer cells our results suggest that mt protein levels of peripheral blood lymphocytes as determined by this flow cytometric method may be used to assess human exposure to toxic metals and to characterize various quantitativequalitative aspects of the response of individuals to cadmium and possibly to other types of environmental stresses | 19|31|41|55|63 | cysteinerich|physical|exposure|blood lymphocytes|flow cytometry |
the use of pesticides in agriculture has increased over the last decade their widespread often uncontrolled use causes thousands of people to be daily exposed to environmental agricultural chemicals resulting in acute and chronic health effects at present there is a paucity of data on the potential adverse effects of exposure to low levels of mancozeb for prolonged periods in order to investigate the effects of mancozeb SE on pulmonary wildlife populations tracheas and lungs of nine to yrold nonmigratory pigeons raised near peach orchards and vineyards repeatedly sprayed with the fungicide were examined the exp situation allowed us to evaluate the longterm natural toxicity of mancozeb as a sentinel for human populations occupationally exposed to fungicides the use of nonmigratory pigeons may serve as an important biological source from which helpful data may be obtained for assessing risks to human health and gaining new insight into pathogenetic mechanisms | 67|95 | exposure|experimental |
prolonged hyperglycemia results in a number of diabetic complications including retinopathy pericyte degeneration is one of the earliest histological changes observed in the development of diabetic retinopathy increased FRs generated under hyperglycemia could damage the retina which abounds in polyunsaturated fatty acids in the current study a severalfold increase in thiobarbituric acidreactive substances was found in rat retina cultured in hyperglycemic medium which decreased significantly when trolox an amphipathic antioxidant was included in the medium to examine the contribution of oxidative stress in vivo diabetic rats were fed trolox in the diet during the course of the experiments after mo of HG whole mounts of retinal vessels were prepared and endothelial cells e and pericytes p were counted the ratio of ep in the retinas obtained from normal rats diabetic rats and diabetic rats fed trolox were and respectively a significant restoration of pericytes by trolox suggests the involvement of oxidative injury during pericyte loss in DR | 28|101|156 | free radicals|hyperglycemia|diabetic retinopathy |
kashinbeck disease kbd an endemic chronic osteoarthritic disorder with necrosis of chondrocytes commonly occurs in china the humic substance present in the drinking water of endemic areas has been proposed as one of the causative AF in this study an in vitro CC system was used to investigate the damaging effects of SHA ha a constituent of humic substance on cultured rb articular chondrocytes the commercial aldrich humic acid aha was fractionated with a series of organic solvents including nhexane benzene ethyl acetate and methanol among the several fractions of aha the ethyl acetate fraction ahaea displayed the most potent inhibitory effect on the survival of chondrocytes in clonogenic assays cellular injury induced by ahaea was evaluated by measuring cell viability with methylthiazol tetrazolium mtt and by determining the release of intracellular lactate dehydrogenase ldh incubation of chondrocytes with ahaea microgml for h produced a concentrationdependent decrease in cell viability and increase in ldh release in addition ahaea triggered lipid peroxidation manifested by elevated malondialdehyde mda formation in CL CA ahaea at the concentrations of microgml caused to fold increases of luminolamplified CL responses which are considered to reflect the production of hydrogen peroxide ho moreover pretreating the cells with uml of catalase significantly prevented the loss of cell viability while superoxide dismutase sod enhanced the adverse effect of microgml ahaea data suggest that the injury to chondrocytes induced by ahaea may be first through o production which is then converted into ho thus initiating lipid peroxidation and leading to chondronecrosis observed in kbd | 35|42|52|61|168|169|182 | factors|cell culture|humic acid|rabbit|chemiluminescence|assay|chemiluminescence |
the biochemical effects of hydrogen sulfide were investigated by treating enzyme homogenates and synaptosomes prepared from rat brain with sodium sulfide brain cytochrome c oxidase activity was highly sensitive to inhibition by sodium sulfide as demonstrated by an ic of microm sodium sulfide was also found to inhibit carbonic anhydrase activity in cerebellum frontal cortex and hippocampus synaptosomal oxygen consumption was significantly reduced as the concentration of sodium sulfide was increased from to microm this was accompanied by a concentrationdependent depolarization of the synaptosomal mitochondrial membrane in situ and a reduction in synaptosomal atp concentration in other experiments using synaptosomes sodium sulfide caused a significant calciumindependent increase in the extracellular accumulation of lglutamate inhibited nadependent uptake of hglutamate but was unable to influence intrasynaptosomal free ionic ca parallel studies conducted in vivo showed that rats exposed over a d period to hydrogen sulfide ppm for hd had significantly higher concentrations of lglutamate in the hippocampus compared to control animals in summary our results indicate that sulfide causes extensive disruption to respiratory and related mitochondrial functions in mammalian BB in vitro the reduced capacity of nerve endings to take up lglutamate may contribute to the raised lglutamate levels observed in vivo | 16|177 | mammalian|brain |
to evaluate the role of cytopathology and its different sampling techniques in the diagnosis of wegeners granulomatosis we retrospectively reviewed cytologic specimens from patients with an established diagnosis of wegeners granulomatosis the smear background cellular composition and accompanying reactive changes were evaluated the majority of the smears were characterized by a bloody background with necrotic debris and extensive acute inflammation large sheets of exfoliated reactive pneumocytes and bronchial epithelium were commonly present multinucleated giant cells and epithelioid histiocytes were present in and specimens respectively numerous hemosiderinladen histiocytes were present in variable numbers in most cases and were abundant in cases bronchial brush and lavage were the best sampling techniques although fineneedle aspiration best demonstrated the granulomas only of the aspirates were diagnostic the combination of cytologic findings negative cultures and elevated titers of antineutrophil cytoplasmic antibody with a cytoplasmic DP may serve to establish a presumptive diagnosis of wegeners granulomatosis | 139 | pattern |
loss of p and pwaf expression have previously been reported in pancreatic adenocarcinoma despite these findings in several reports of oncogene and RT suppressor gene alterations in pancreatic cancer the clinical significance of these changes is still poorly understood in an attempt to detect molecular prognostic markers for PC we studied the immunohistochemical expression of p pwaf and tgfbeta proteins in pancreatic adenocarcinomas of the ductal type the results were correlated with clinicopathologic findings to identify the markers with prognostic significance p nuclear immunoreactivity was seen in of the cases and it was strong to moderate in of them pwaf cytoplasmic positivity was found in of the tumors with staining strong to moderate tgfbeta stained the cytoplasm of the tumor cells in of the pnegative cases exhibited pwaf expression in of cases tgfbeta reactivity was seen in the absence of p and pwaf p positivity identified tumors of higher grade but did not correlate with stage or survival tgfbeta expression however identified lowgrade tumors and patients with longer survival no rho was found between the expression of any of these molecular markers and smoking history we report a significant correlation between tgfbeta reactivity and lowgrade tumors and between tgfbeta and better survival this is a novel finding pointing to tgfbeta as a possible new stageindependent predictor of RT survival in pancreatic ductal adenocarcinoma in agreement with others we also found p mutation in of the PT | 22|48|170|217|235 | tumor|pancreatic carcinoma|correlation|tumor|tumors |
ki is a proliferation marker that is often used to estimate the growth fraction of PT and other tissues this antigen is expressed during all phases of the cell cycle but not in quiescent g cells many studies fail to indicate that the ki antigen can be expressed even when dna synthesis is blocked we studied the expression of the antigen ki in cyclearrested osteosarcoma cells we found that these cells are positive for ki even when they are arrested in gs or gm by using synchronizing inhibitors by inducing pwafcip in a tetracyclineregulated expression system or by inducing wild type p and p after inflicting dna damage our results show that not all cells containing the ki antigen are actively proliferating cells and we advise against the use of ki in studies on cells that overexpress p or p | 15 | tumors |
we sought to determine the sensitivity and specificity of immunohistochemistry using the tordji moab biogenex san ramon calif which is specific for the c protein of the HC virus compared with reverse transcriptasepolymerase chain reaction rtpcr of tissue for viral rna rtpcr had been performed on fixed tissue specimens immunohistochemistry was performed using prediluted antibody with the ALP phosphatasefast red biogenex technique predigestion with protease xxiv biogenex and other procedures followed the manufacturers protocols positive immunohistochemistry was narrowly defined as tightly clumped perinuclear red granules in HCs of the specimens were positive by rtpcr with rtpcr as the standard of comparison immunohistochemistry yielded a sensitivity of and specificity of positive cells when present were usually very rare with stringent criteria immunohistochemistry with the tordji monoclonal antibody is a very specific fairly sensitive diagnostic test for HC virus in fixed CL tissues | 27|57|86|135|139 | hepatitis c|alkaline|hepatocytes|hepatitis c|liver |
the gross features of prostatic adenocarcinoma can be subtle while these gross features have been described the histologic correlates have not been detailed this T0 involved examination of consecutive RP specimens between january and december the gross findings were correlated with histologic examination no gross lesion was apparent in cases a subtle lesion was present in and a definite lesion suggestive of carcinoma in RT was identified grossly and confirmed histologically in of subtle lesions of definite lesions and in of all prostatectomy specimens prostatectomy specimens with definite lesions were significantly more likely to contain PT that were stage t or higher than those with a subtle lesion were higher grade mean gleason score vs and had larger tumor diameters mean cm vs cm specimens with subtle lesions were more likely to contain tumors that were stage t or higher compared with specimens with no apparent gross lesions vs but did not differ significantly in mean gleason score vs or RT size cm vs cm ninetytwo percent of all tumors stage t or higher of all tumors gleason score or higher and of all tumors greater than cm in diameter were grossly identified and confirmed histologically however the site of EPE and positive margins were present in the histologic sample of the grossly identified lesion in only of cases and of cases respectively prostatic adenocarcinomas can be accurately identified by gross inspection in of cases the falsepositive rate for gross inspection was the presence of an identifiable gross lesion is correlated with increased tumor stage grade and size | 24|29|64|95|160|200 | study|radical prostatectomy|tumor|tumors|tumor|extraprostatic extension |
routine diagnosis of pathology images transmitted over telecommunications lines remains an elusive goal part of the resistance stems from the difficulty of enabling image selection by the remote pathologist to address this problem a telepathology microscope system telepath telemedicine solutions birmingham ala that has features associated with static and dynamic imaging systems was constructed features of the system include near real time image transmission provision of a tiled overview image free choice of any fields at any desired optical magnification and automated tracking of the pathologists image selection all commands and images are discrete avoiding many inherent problems of full motion video and continuous remote control a set of slides was reviewed by pathologists in a simulated frozen section environment each pathologist provided diagnoses for all slides as well as qualitative information about the system thirtyone of diagnoses disagreed with the REF diagnosis that had been reached before the trial began qf the were deferrals and were diagnoses of cases that had a deferral as the REF diagnosis in cases the diagnosis disagreed with the reference diagnosis yielding an overall accuracy of confidence levels in the diagnoses were high this trial suggests that this system provides highquality anatomic pathology services including intraoperative diagnoses over telecommunications lines | 141|166 | reference|reference |
to study the comparative value of the levels of cardiac troponin i ctni creatine kinasemb isoenzyme ckmb and myoglobin in the detection of acute ischemic myocardial injury we serially measured plasma concentrations of these cardiac proteins in pigs with myocardial ischemia subtending severe PD stenoses and in pigs with a sham operation performed but without CAS in the stenosis group flow in the LAD lad artery was reduced by and maintained for hours n days n or weeks n flow in the coronary artery was measured by a flowmeter and regional left VVI dysfunction was monitored by echocardiography myocardial infarction was identified with triphenyltetrazolium chloride staining all pigs with stenosis of the lad had significant ultrastructural CA consisting of loss of myofibrils and an increase in mitochondria and glycogen deposition cardiac proteins were released in all pigs with stenosis of the lad artery during the OD of myocardial ischemia the levels of ctni ckmb and myoglobin increased significantly relative to the baseline the sensitivity and specificity for ctni were higher than for ckmb or myoglobin results of this study show that ctni is the better marker for the detection of acute ischemic myocardial injury increased C2 of ctni can be found in reversible and irreversible myocardial ICM injury in this model | 43|55|63|92|116|145|195|206 | coronary artery|coronary artery stenosis|left anterior descending|ventricular|abnormalities|development|levels|ischemic |
the microparticle enzyme immunoassay meia for digoxin abbott laboratories abbott park ill requires no sample i.c.v. and is widely used in clinical toxicology laboratories for monitoring serum digoxin concentrations one advantage of the new meia is the lower crossreactivities with such crossreactants as digitoxin oleandrin and bufalin compared with the FPI fpiafor digoxin digitoxin oleandrin and bufalin showed positive crossreactivity with meia and fpias for digoxin in the absence of the primary analyte digoxin a surprising finding was that digoxin concentrations were falsely decreased by these crossreactants when serum pools containing digoxin were supplemented with various concentrations of these crossreactants and when digoxin concentrations were measured by the meia in contrast digoxin concentrations were falsely elevated when measured by the fpia for example when a SS pool containing nmoll of digoxin was supplemented with nmoll of bufalin the apparent digoxin concentrations were nmoll with the meia and nmoll with the fpia taking the advantage of only protein binding of digoxin and more than protein IB of digitoxin and bufalin we demonstrated that monitoring free digoxin instead of total digoxin eliminated negative interference of digoxin by these crossreactants in the meia and positive interference in the fpia although oleandrin is also strongly bound to serum protein high concentrations of oleandrin still modestly affect the free digoxin assay for both meia and fpias | 15|50|125|164 | pretreatment|fluorescence polarization immunoassay|serum|binding |
serial bone marrow aspirates from patients previously given a diagnosis of acute lymphoblastic leukemia all who had undergone chemotherapy bone marrow transplantation bmt or both were analyzed by multidimensional flow cytometry mdf to detect residual disease lower limit of detection correlation between the results of morphologic examination and mdf showed concordant results on of specimens the mdfpositive morphologic examinationnegative specimens were positive by cytogenetic examination or were obtained from patients in whom the all eventually relapsed similar correlations between mdf and the results of cytogenetic examination were obtained leukemic cells were detected in of patients before bmt and of after bmt normal regenerating lymphoblasts were identified and quantified by mdf in patients without detectable leukemic lymphoblasts patients with leukemic lymphoblasts found by mdf in specimens obtained immediately before bmt were times more likely to experience relapse after bmt compared with mdfnegative patients even when leukemic lymphoblasts were undetectable by histopathologic examination cytogenetic examination or both all patients who had undergone bmt with leukemic lymphoblasts found by mdf with or without morphologic or cytogenetic confirmation experienced relapse according to conventional criteria within days of the mdf analysis the detection of residual disease before overt relapse may provide information for EI while definitive recognition of normal recovering blasts may prevent unnecessary treatment | 198 | early intervention |
patients with wiskottaldrich syndrome a severe inherited immunodeficiency disorder have a markedly increased risk of developing nonhodgkins lymphoma compared with the general population these are uniformly diffuse aggressive bcell neoplasms that resemble those seen in aids and the posttransplantation setting and also may be associated with epsteinbarr virus we report what to our knowledge is the first case of follicular lymphoma in a yearold child with wiskottaldrich syndrome the neoplasm was composed predominantly of large cells with immunoblastic features and it possessed CS chainrestricted surface immunoglobulin clonal immunoglobulin gene rearrangements and a t the RT lacked epsteinbarr virus sequences by in situ hybridization and southern blot terminal repeat analysis interestingly however the RT contained cmyc gene rearrangement | 82|94|112 | light|tumor|tumor |
autologous blood donation before elective surgery is generally believed to be a safe procedure for patients with a variety of underlying medical conditions but the accumulation of additional data continues to define its safety in unique patient groups patients who have received a solid organ transplant may also undergo various elective surgical procedures after transplantation and the question of safety of autologous blood donation for these patients is raised in one hospitalbased blood collection program we identified patients who had received solid organ transplants and subsequently made autologous blood donations for elective operations unrelated to the transplantation two patients had received heart transplants and received CL transplants a total of autologous donations were made by these patients without adverse effects or complications a low hemoglobin concentration was the only reason for temporary deferral from autologous donation despite having complicated clinical situations recipients of solid organ transplants can safely donate autologous blood and should not be automatically excluded from making such donations | 105 | liver |
whether it is necessary to adjust the citrate volume in blood collection tubes for patients with anemia is unknown however the standard of care is not to adjust the volume we compared the prothrombin time pt and activated PTT time aptt test results of nonadjusted and adjusted citrate amounts in specimens from patients who are severely anemic samples were drawn into a citrate volume and if the hematocrit was less than additional samples were drawn into adjusted citrate tubes the pt and aptt were run on pairs of specimens and the rho coefficient was for both assays a statistically significant difference was noted between sample results collected in evacuated tubes in which the citrate volumes were adjusted to the hematocrit vs those in which it was not however when the difference between sets of values was plotted against the hematocrit there was no correlation there seems to be no need to change the standard practice for obtaining coagulation specimens into citrate for patients who are anemic | 38|91 | partial thromboplastin|correlation |
the use of reconstructed human epidermis provided the basis for an in vitro MM of human cutaneous candidosis candida albicans blastospores on the surface of reconstructed human epidermis provoked the following changes within h SF keratin degradation scaling hyperkeratosis parakeratosis dyskeratosis representing hyperproliferative AS spongiosis and vesiculation great differences in the intensity of these reactions of intact reconstructed human epidermis or chemically or mechanically damaged reconstructed human epidermis illustrate the importance of the SC as a barrier uninfected reconstructed human epidermis showed prominent cell proliferation representing wound healing h T3 mechanical or chemical i.c.v. these signs of repair were blocked in the presence of c albicans and the blastospores were able to invade the stratum corneum when desmosomes were accessible a high affinity of c albicans blastospores to these structures was observed a single application of an econazole liposome dispersion decreased scaling hyperkeratosis and dyskeratosis morphological alterations of c albicans blastospores T3 treatment with the econazole liposome dispersion in the proposed ill vitro model were identical as described in established animal models this reconstructed human epidermis MM of cutaneous disease may provide insight into the pathogenesis and treatment of cutaneous candidosis and may provide a substitute for animal models and investigations on humans | 13|34|43|73|89|93|151|176 | model|superficial|stress|stratum corneum|after|pretreatment|after|model |
conventional methods for the diagnosis of mycobacterium tuberculosis infections have serious limitations to determine whether amplification of m tuberculosis dna in serum by the polymerase chain reaction pcr might be a useful additional diagnostic tool we tested clinical specimens using primers TPS for the is insertion sequence of the m tuberculosis complex the samples consisted of serum samples from HCs serum samples from patients with diagnoses other than tuberculosis including immunosuppressive disorders samples from patients with a clinical picture suggestive of tuberculosis and serum samples from patients with proven m tuberculosis infection both serum and representative samples from anatomical regions suspected of being INF were collected from a further patients for comparison with serum pcr serum pcr identified confidence interval ci patients with proven tuberculosis and ci patients with suspected tuberculosis in the group of patients with other diagnoses ci tested positive while none of the specimens from the healthy control group were positive ci serum pcr results also compared favourably with other clinical specimens obtained from the same patient serum pcr can therefore be a useful additional technique for the early diagnosis of m tuberculosis infection but it does not necessarily indicate active infection | 41|59|103 | specific|healthy controls|infected |
CDAD cdad is primarily a nosocomial condition communityacquired disease has been reported but the incidence is felt to be low and the rate of disease resulting in hospitalization is reported as negligible we recently experienced a month outbreak of cdad january to june patients were involved and four deaths were attributable to pseudomembranous colitis early in the outbreak period we were aware that many new admissions presented with c difficile cytotoxin b positive diarrhoea in some cases this was the sole reason for hospitalization this observation forms the basis of this report | 0 | clostridium difficileassociated disease |
a large singlesource salmonella outbreak caused by a rare serovar bovismorbificans r occurred in southern finland in the origin of the outbreak was sprouted alfalfa seeds a questionnaire was mailed to all subjects with positive stool SC ninetyone percent returned the questionnaire one hundred and fiftythree were adults one hundred and fiftynine out of one hundred and ninetyone reported diarrhoea fever abdominal pains fatigue articular PS and had no symptoms the median duration of diarrhoea was days range that of other symptoms days range those reporting articular symptoms were examined patients or contacted by telephone patients twelve percent fulfilled the criteria for reactive arthritis rea the difference in the incidence of rea between children and adults was not significant vs the median onset of joint PS was days PS were oligoarticular in and polyarticular in four patients mostly rea was mild but in four patients the joint symptoms lasted for more than months ten rea patients had hlab tPA the duration and severity of rea did not differ between hlab positive and negative patients fourteen rea patients had received fluoroquinolone treatment before reactive joint or tendon symptoms manifested but this treatment did not prevent rea PS | 36|65|125|128|158|195 | culture|symptoms|symptoms|symptoms|tissue type|symptoms |
although neurological symptoms in brucellosis are frequent central nervous system cns involvement is uncommon five patients with neurobrucellosis are presented three patients presented with meningoencephalitis one with polyradiculoneuritis and one with myelitis and an eighth nerve palsy all patients had lymphocytic pleocytosis low gl and elevated levels of protein in the cerebrospinal fluid csf gammaglobulin and igg values in the csf were also increased results of agglutination tests for brucella in SS and csf were positive for all patients although titres were less in the csf brucella melitensis was cultured from two patients treatment included concurrent administration of three of the following drugs doxycycline rifampicin streptomycin cotrimoxazole ceftriaxone or ciprofloxacin the three patients with meningoencephalitis fully recovered the other two patients were left with minor disability | 43|71 | glucose|serum |
the diagnosis and treatment of pneumonia in mass gathering situations is a medical challenge requiring prompt decision making and knowledge of the aetiology we studied cases of pneumonia admitted to two hospitals during the pilgrimage hajj season to makkah sixtyfour patients were enrolled in the T0 of which were men with a mean age of years range nearly all were from developing countries diagnosis was established in patients with mycobacterium tuberculosis being the commonest causative organism followed by gramnegative bacilli streptococcus pneumoniae accounted for only with legionella pneumophilia mycoplasma pneumoniae and viruses accounting each for the main finding of this study is that m tuberculosis is a common cause of pneumonia under these unusual extreme circumstances its presentation was acute and indistinguishable from pyogenic pneumonia thirtyone per cent of TB cases had upper lobe involvement lower lobe and multilobar this was similar to the radiographic features in nontuberculous pneumonia cases all but one patient with tuberculosis recovered following the administration of firstline antituberculous drugs the total mortality was the preponderance of m tuberculosis and gramnegative bacteria over s pneumoniae may reflect the prior use of amoxycillin and the effect of exhaustion malnutrition and old age | 45|129 | study|tuberculous |
the rate of cd tlymphocyte decline seen in hivinfected patients is very VL although older patients a longer duration of hiv infection and a high level of plasma viraemia have been associated with a faster fall in cd tcells the relationship between these variables is still not well known | 12 | variable |
we reviewed the clinical record of all patients admitted to saga medical school hospital during the most recent years and found that were diagnosed as having necrotizing fasciitis bacteriological examination demonstrated that vibrio vulnificus was the pathogen responsible in five patients the disease caused by v vulnificus occurred in the warmer half of the year all of the patients had underlying chronic liver dysfunction and three of them had previously consumed raw seafood in these patients the predominant skin lesions were oedema and subcutaneous bleeding such as ecchymosis and purpura while superficial necrosis was not recognized three patients died of SVR complications by contrast all of the five patients with necrotizing fasciitis caused by streptococcus pyogenes had the disorder in winter and only one of them had chronic liver dysfunction in skin lesions subcutaneous one was rare but necrosis was seen often despite the high incidence of SVR complications no patients with streptococcal necrotizing fasciitis died these findings suggest that the clinical features of necrotizing fasciitis caused by v vulnificus are different from those of necrotizing fasciitis caused by classical pathogens and that the two should be differentiated as early as possible to improve the prognosis | 100|134|147 | systemic|bleeding|systemic |
the objective of the study was to obtain detailed descriptive epidemiological information on sporadic verocytotoxinproducing escherichia coli o infection in scotland in relation to transmission routes and hostrelated risk AF using a standardized questionnaire the study was carried out throughout scotland over an month period from july and coordinated at the communicable diseases and environmental health scotland unit glasgow cdehsu the subjects were laboratoryconfirmed cases of escherichia coli o infection of whom met the criteria for inclusion in the T0 the most important findings were the high proportion of cases who had been exposed to environmental AF such as farm animals andor their byproducts or who had participated in gardening or gardenplay or who had suspected or confirmed household water supply problems prior to the onset of illness the frequency and relative importance of environmental risk factors requires further quantification and study in order to assess where control measures can be directed most effectively the implications for the nhs in preventing this crippling lifethreatening infection are considerable not least in relation to hospitalization dialysis and renal transplantation costs | 29|79|96 | factors|study|factors |
a hivpositive patient presented with CM that was not detected by cerebrospinal fluid csf latex antigen and direct microscopy the diagnosis was confirmed by culture of the csf and subsequent urine culture both of which yielded an apparently acapsular strain of cryptococcus neoformans T3 months the patient relapsed and capsulated yeasts were observed on this occasion on direct microscopy of the csf the latex antigen test was strongly positive SC again yielded an apparently acapsular isolate retrospective SC of all isolates obtained from this patient in sterile csf resulted in the formation of capsules this was confirmed by the requirement of normal non heat inactivated serum for neutrophilcryptococcus attachment to occur in vitro although antigen and direct microscopy are frequently relied upon to diagnose cryptococcal meningitis a negative result does not exclude the condition | 5|43|69|77 | cryptococcal meningitis|after|culture|culture |
ecthyma gangrenosum is a characteristic skin lesion that is caused by pseudomonas aeruginosa p aeruginosa in the majority of cases systemic p aeruginosa usually complicates debilitating conditions like leukaemia burns and cystic fibrosis we report a patient with underlying hypogammaglobulinemia who developed ecthyma gangrenosum secondary to p aeruginosa septicaemia which was potentially lifethreatening recognition of the characteristic skin lesions with prompt initiation of AGA antibiotics and intravenous immunoglobulins were lifesaving a review of the english literature reports three other cases of ecthyma gangrenosum in patients with underlying hypogammaglobulinemia | 63 | appropriate |
burkholderia pseudomallei is an important human pathogen in tropical Az particularly south east asia and RNA australia a fatal case of meliodosis presenting as BB abscesses is described the patient deteriorated despite treatment and died days after admission burkholderia pseudomallei was only isolated after administration of corticosteroids whilst on treatment with antibiotics to which the organism later showed in vitro sensitivity magnetic resonance imaging was more sensitive than computed tomography in diagnosing early brainstem infection in this patient physicians working outside the endemic areas must be attuned to the possibility of melioidosis in any patient with an appropriate history of travel to endemic Az the combination of striking early extensive confluent t hyperintensity with disproportionately small enhancing lesions may be characteristic of meliodosis | 9|15|24|103 | areas|northern|brain|areas |
amoebic CL abscesses ala are characteristically large lesions at presentation but their OD in man has not previously been described we present a case of an ala that over the course of days developed from an undetectable lesion to a cm diameter lesion this clinical history suggests that the pathogenesis of alas may pursue an acute rather than a chronic course | 1|12 | liver|development |
we report a case of postanginal septicaemia complicated by bronchopneumonia and haemophagocytosis in a year old male presenting with severe thrombocytopenia we believe that this is the first reported case of TP due to haemophagocytosis in this unusual condition | 31 | thrombocytopenia |
we describe a yearold male who developed native valve infective endocarditis due to staphylococcus capitis as a consequence of repeated oesophageal dilatation the patient was treated with AGA antibiotic therapy but his condition deteriorated and he died we review previously reported cases of IE associated with upper endoscopy and discuss the issue of prophylaxis of high risk patients prior to upper endoscopy involving various invasive procedures eg biopsy dilatation and sclerotherapy | 27|43 | appropriate|infective endocarditis |
HIVE associated with dengue fever is considered to be a rare condition in adults we describe a patient with a primary dengue infection who in the absence of overt signs of dengue shock syndrome died due to progressive cerebral oedema autopsy findings demonstrated loss of integrity of CBF V1 endothelium and involvement of complement activation | 0|47|48 | encephalopathy|cerebral|vascular |
congenital ataxias ca are rare predominantly nonprogressive syndromes characterized by marked hypotonia developmental delay followed by the appearance of ataxia most children show marked speech and cognitive developmental problems non progressive ca npca can be divided into pure ca without additional symptoms and syndromes with ca pure ca can be due to cerebellar malformations as hereditary or nonhereditary cerebellar hypoplasia dandy walker syndrome or occasionally supratentorial abnormalities ataxic syndromes are less frequent but more distinctive there are syndromes eg joubert syndrome where ataxia is a cardinal feature and others where ataxia is only an occasional symptom acquired ataxias due to congenital CMV or perinatal problems form a small third group in about half of all cases with npca aetiology and inheritance are still unknown diagnosis of npca is made by a typical PH and careful CE diagnosis of a more distinctive ataxic syndrome may be possible on clinical grounds neuroimaging with special attention to the posterior fossa will aid accurate clinical classification early progressive ataxias require careful differentiation from other types | 101|132|135 | cytomegalovirus infection|history|clinical examination |
tuberous sclerosis is a heredofamilial neurocutaneous syndrome or phakomatosis with multisystem involvement including the brain kidney skin retina heart lung and bone the brain is the most frequently affected organ in tuberous sclerosis brain lesions in tuberous sclerosis are of three kinds cortical tubers VWM abnormalities and subependymal nodules we review the computed tomography ct and magnetic resonance mr features of the brain lesions in patients with tuberous sclerosis ct clearly demonstrates calcified subependymal nodules mr imaging demonstrates more clearly cortical and WG matter lesions than ct since mr imaging shows excellent image contrast between various normal structures and high sensitivity in detecting pathological states due to intrinsic differences in PD and in particular in proton EC50 times of tissues possible pathogenesis of this disorder is also discussed | 44|82|110|116 | white matter|white|proton density|relaxation |
the anticonvulsant action of felbamate and mgkg ip was tested against motor seizures induced by pentylenetetrazol in five agegroups of rats and days old in AD rats felbamate suppressed GTC seizures leaving intact minimal clonic seizures in all groups of rat pups FBM exhibited a specific action against the tonic phase of GTC seizures in addition the highest dose of felbamate was found to suppress minimal seizures in dayold rats the changes of felbamate action during ontogeny might be due to multiple mechanisms of anticonvulsant action with an uneven developmental profile | 25|29|42|52 | adult|generalized tonicclonic|felbamate|generalized tonicclonic |
in this paper the results of an extensive medical investigation of children with childhood autism are presented and compared with those found in a group of nonautistic individuals matched for sex age and intellectual level all referred for developmental deviancy of unknown etiology the examination included a psychiatric assessment and a neurological examination in addition to neurophysiological chromosomal metabolic and neuroimaging evaluation in the clinical examination macrocephaly was found only among the autistic individuals while the frequency of pathological cerebral ct and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group all the other pathological findings were found to occur with the same frequency in the two CG except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism based on the present findings ordinary procedures for assessment of developmentally delayed children should be followed this should include a systematic clinical neuropaediatric examination an assessment of vision and hearing and a chromosome study including that for fragile x | 114 | groups |
to investigate maturational change in the susceptibility of voltagedependent calcium ca channels vdcc in the BB to excessive depolarization which is likely to occur during hypoxia or ischemia we studied depolarizationinduced increases in ca concentration in cortical synaptosomes cai obtained from young and dayold and adult rats using fura am as a ca indicator the effects of ca antagonists on the increase were also studied the maximal increase in cai caused by mm kclinduced depolarization was significantly lower in dayold rats nm compared with that in adult rats nm on the other hand the time necessary for cai to decrease to of its maximal level tau was significantly shorter in immature rats compared with that in adult rats and was particularly short in and dayold rats and min vs for adult rats the maximal increase in cai in dayold rats and tau in adult rats were markedly reduced by verapamil omegaagatoxin iva and omegaconotoxin gvia antagonists of l p and ntype ICa respectively to similar extents while a mixture of the three antagonists markedly decreased both maximal increase and tau in and dayold and AD rats these results indicate that depolarizationinduced ca influx through vdccs in immature rat brain is less pronounced than that in AD rats and suggest that the susceptibility of all of l n and ptype ca channels is increased during maturation in the first few weeks T3 birth this lower susceptibility to depolarization might be involved in the resistance to hypoxia in immature animals | 15|161|184|205|230 | brain|ca channels|adult|adult|after |
we describe a boy who has gelastic epilepsy precocious puberty hypothalamic hamartoma and agenesis of the corpus callosum we believe that this is the first documented case in which agenesis of the CC has been associated with Thy hamartoma and gelastic epileptic syndrome in a child | 32|37 | corpus callosum|hypothalamic |
we report the youngest known case with balós con sclerosis balós disease a variant of multiple sclerosis this yearold japanese boy was diagnosed by clinical manifestations and by characteristic findings on magnetic resonance imaging mri dexamethasone was given intravenously mg twice daily for days the clinical manifestations were resolved within weeks and the mri findings were markedly improved T3 weeks following the initiation of steroid therapy he showed remarkable clinical and PCS improvement it cannot be excluded that the clinical improvement resulted from the steroid therapy | 8|58|71 | concentric|after|physical |
the authors describe a case of early ON ataxia with CA and VE deficiency treated with alphatocopherol supplementation and physically rehabilitated by postural biofeedback clinical assessments SS VE levels and postural evaluation by means of a stabilometric platform continued for about years and significant clinical improvement was recorded our study confirms that combined PT and vitamin e supplementation may result in improvement of cerebellar function motor improvement is directly related to vitamin e SS levels providing further confirmation that normal vitamin e levels are crucial for proper BB functions | 7|10|12|26|27|53|73|87 | onset|cerebellar atrophy|vitamin e|serum|vitamin e|physical therapy|serum|brain |
AD male rats were fed one of five diets varying in fat composition purina chow or soy bean oil CO MO or olive oil added to chow for weeks T3 days of access no differences between CG were found in CS measured at light ON and light offset during week restraint stress tests were performed highfat diets promoted significantly higher stimulated corticosterone levels during week all rats were given an oral glucose tolerance test rats fed the corn and soybean oil diets had significantly elevated blood gl h after gl intubation euglycemia was restored after hours in all but the soybean oil group during week a second stress test was performed no differences in initial stress responsivity was observed but groups fed the menhaden soybean and olive oil diets had significantly higher corticosterone h after the end of restraint the CO olive oil and soybean oil diets promoted transient hyperphagia by the end of the experiment the group fed the menhaden oil diet weighed significantly less and ate less than the remaining groups these data demonstrate that AS responsivity is briefly enhanced during initial access to the highfat regimens continued highfat FF results in an impaired ability to restore basal corticosterone following stress | 0|19|20|29|36|40|44|86|89|140|177|191 | adult|corn oil|menhaden oil|after|groups|plasma corticosterone|onset|glucose|glucose|corn oil|stress|feeding |
five thousand and eighteen quadruplet daily measurements of lowerleg length of female and male rats were performed in order to characterize shortterm growth within a short time growth proceeds irregularly and consists of multiple incremental bursts mini growth spurts with no evidence for strict periodic behavior mini growth spurts are sshaped incremental patterns that can be characterized by doubleexponential functions gompertzs functions gompertzs functions are sshaped and can be defined by three parameters that identify amplitude inflection point age at peak growth velocity and Mw the latter not only refers to the rapidity of each incremental burst but also alludes to the duration that one incremental burst needs for completion in regard to these characteristics mini growth spurts differ significantly between the sexes in rats mean amplitude of mini growth spurts was microm sd microm in female rats and microm sd microm in male rats peak growth velocity of mini growth spurts appeared lower in male rats than in female rats female rats showed mean gamma of sd whereas male rats showed mean y of sd partial growth hormone deficiency led to a modification in rats that was reversed when exogenous growth hormone was administered mean intervals between subsequent mini growth spurts ranged between and days but the large R2 of these intervals sd between and days and the fact that neither spurtspurt interval nor spurt amplitude appeared predictable strongly suggest chaotic behavior of mini growth spurts | 84|209 | slope|variation |
endogenous analgesia induced by changes in motivation has been identified in the chicken in previous studies but either the motivational changes were difficult to interpret or the motivation was unpredictable experimental sodium urate su ICA of the ankle joint resulted in paincoping behaviour onelegged standing or sitting for a h period in nonfooddeprived birds without access to food complete analgesia or marked hypoalgesia was observed in birds which had been food deprived overnight and given access to food immediately after su i.t. this analgesia seen during feeding behaviour in the fooddeprived bird could be completely reversed by i.v. of naloxone these results demonstrate that feeding motivation can totally suppress in some animals the severe tonic pain of su arthritis and that this analgesia may be opioid mediated | 34|81|97 | arthritis|injection|intravenous injection |
senescenceaccelerated mice sam p and r were behaviorally assessed in a crosssectional T0 at and months of age behavioral measures included memory place discrimination and repeated acquisition in a WM sensorimotor performance turning in an alley traversing bridges wire rod hanging and falls from a wire screen psychomotor performance openfield exploration and emotionality entries in a plus maze grooming and defecation in a plus maze and in an open field in the water maze aged p mice were impaired in place discrimination and in repeated acquisition tasks demonstrating evidence of an agerelated decline in spatial SM processing abilities the demonstration of this impairment however was complicated by noncognitive factors such as the tendency of many older p mice to float sensorimotor skill impairment was accelerated with age in p mice but not in r mice and this impairment was present despite the lack of agerelated changes in body weight in p mice although p and r mice were not different in GA activity at old age p mice were substantially more hyperactive in an open field and in the plus maze than r mice when compared at young age independent of age p mice demonstrated a reduction of ALB in the plus maze taken as a whole the data suggest that although agerelated behavioral alterations occur in the p mice some of these changes are evident at months of age thus the behavioral abnormalities that exist not only represent an accelerated aging phenomenon but may also be considered a developmental pathology | 12|29|95|161|198 | study|water maze|memory|general|anxietylike behavior |
the relationship between plasma testosterone levels and locomotor activity in wildcaught sexually mature male meadow voles microtus pennsylvanicus was assessed in the laboratory several aspects of locomotor activity were monitored for h on two consecutive days using the automated digiscan activity monitoring system plasma testosterone C2 were determined immediately following the second day of activity monitoring significant pearson correlations were obtained between plasma testosterone C2 and total distance traveled r p and amount of time spent in movement r p on the second day the wild voles showed a reduction in activity levels from the first to the second day of activity monitoring which is indicative of habituation to a novel environment this study provides direct evidence for a significant correlation between laboratory measures of behavioral activity and plasma testosterone levels in a wildcaught rodent these findings indicate that previous assessments of hormonebehavior relationships in laboratorybred rodents are consistent with the relationship between hormones and behavior in wild rodents | 45|64 | levels|levels |
a shortterm fluidintake test is described which is directed at the study of individual variation in gustation in laboratory mice to avoid position preferences associated with twobottle tests single graduated cylinders are used to present the solution intake of water and solutions is recorded for a h period beginning h prior to the dark phase of the CS cycle the timing of data collection ensures a stable baseline of fluid intake because it coincides with the period in which mice begin to drink food and water are available ad lib at all other times so the test avoids the water restriction that is often used in gustatory studies we report normative data on ten commonly used inbred strains for sucrose mm saccharin mm quinine mm hci and mm nacl mm and monosodium glu mm strain differences were pronounced for all tastants concurrent measures of food and fluid intake by B6 and dbaj mice demonstrated that the shortterm reduction of fluid intake resulting from h quinine administration which was restricted to cblj mice was associated with a minor reduction in food intake during the h test and had no statistically significant effect on food or fluid intake during the h posttest period or during a h period the next day the absence of largescale or persistent nonspecific effects supports the use of the paradigm for screening of multiple solutions on the same animals the reliability of the test is supported by positive correlations between repeated measurements of the same solution across substantial time intervals its ease of use substantial reliability and avoidance of water restriction make the test a very useful addition to screening tools in the field of gustation research | 57|132|149 | light|glutamate|cblj |
both longevans le and wistarfurth wf strains of rat are known to be resistant to development of hypertension by mineralocorticoid mc treatment mcinduced hypertension is in part mediated by the BB we have examined another aspect of central mc action the induction of nacl appetite in these strains by using the more common spraguedawley sd and wistar ws strains for comparison in the first experiment le and sd rats were administered three treatments known to induce an appetite for nacl solution in rats administration of deoxycorticosterone acetate doca increased the intake of m nacl in both strains but the amounts consumed were about fold greater in le rats than in sd rats administration of captopril also increased nacl intake but there were no differences between le and sd rats nacl depletion with furosemide induced nacl appetite in both strains but the amounts consumed were about fold greater in le rats than in sd rats in the second experiment AD male wf and ws rats were administered doca enalapril or furosemide and nacl appetite was determined both strains showed comparable nacl appetite during each of these treatments however during a week regimen of doca with only naclkcl solution to drink uninephrectomized wf rats consumed less than ws rats thus despite reported resistance to mcinduced hypertension neither le nor wf strains of rats showed correspondingly marked deficits in induced nacl appetite | 30|158 | brain|adult |
lurcher mutant mice characterized by degeneration of cerebellar purkinje cells and granule cells were compared to normal littermate controls for different facets of grooming and nongrooming behaviors after a brief period of WI by comparison to NCs the number and the duration of several grooming components were decreased in lurcher mutant mice namely licking the forelimb the abdomen the back and the hindlimb by contrast the number and duration of bodyshaking episodes were not reduced lurcher mutants had fewer grooming elements for bouts with at least five elements however the serial organization of grooming as determined by the order of appearance of grooming elements was maintained in lurcher mutants these results indicate that the cerebellar cortex is involved in the appearance of various grooming elements but not in the organization of the cephalocaudal CS | 32|36|133 | water immersion|normal controls|sequence |
the present study investigated how variations in the period of delay between training and testing in the MWM task affect the use of spatial SM in AD rats that were prenatally exposed to ethanol previous results utilizing the morris water maze task have shown that prenatal or early postnatal SE to ethanol produces deficits in the use of spatial memory a type of SM that is dependent on an intact hippocampus however in these prior studies the delay period between the training of animals and the testing of spatial memory is typically fixed at only day in the current study which utilized a revised training procedure within the morris WM task the period of delay between training and testing was altered such that it was either day or days following the day delay different levels of prenatal exposure to ethanol impaired the use of spatial memory in contrast following the day delay prenatal SE to ethanol failed to impair the use of spatial memory the present study thus shows that prenatal SE to ethanol differentially affects spatial memory in the MWM task depending on the period of delay between training and testing | 17|24|26|49|63|109|153|171|180 | morris water maze|memory|adult|exposure|memory|water maze|exposure|exposure|morris water maze |
to investigate the role of the central ACh system in the regulation of metabolism during exercise we injected atropine x mol into the lateral cerebral ventricle of normal and adrenodemedullated adm UT rats submitted to exercise on a treadmill m min grade until exhaustion concentrations of blood glucose plasma free fatty acids ffa and lactate were measured before and every min T3 the start of exercise for a period of min adrenomedullectomy had no effect on the maximal capacity of exercise mce but atropine administered intracerebroventricularly icv reduced the maximal capacity of exercise of both normal and adm rats in normal rats blood concentrations of gl and plasma free fatty acids remained essentially unchanged compared to the levels at rest whereas in adm rats a rapid increase in plasma glucose and plasma free fatty acids C2 occurred during exercise these data indicate that adrenomedullectomy disrupted the accuracy of the feedback mechanism that regulates the mobilization of extramuscular fuels during exercise in normal rats in addition adm rats showed an increased lipid mobilization as a source of energy during exercise which might explain the increased PG by an inhibition of muscle glucose uptake these results suggest that CE ACh neurons might be involved in the control of SE ATP adjustment during exercise thereby reducing the maximal capacity of exercise in addition the results of this study suggest that the adrenal glands are important for an accurate FB mechanism during exercise | 7|31|61|105|135|184|196|197|206|207|235 | cholinergic|untrained|after|glucose|levels|plasma glucose|central|cholinergic|energy|substrate|feedback |
bxsb mpjyaa and nzbbinj mice have been used as animal models for both developmental learning disability and SVR autoimmune disease approximately of these animals show ectopic clusters of SN in layer i of SC similar to those found in postmortem analyses of human dyslexics and all exhibit an autoimmune condition similar to systemic lupus erythematosus sle in humans the expression of immune disease in the bxsb strain unlike in humans is more severe in males than females most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age when the bxsb females unlike the male bxsb and female and male nzbs are not yet showing high titers of autoantibodies associated with their lupuslike form of autoimmune disease this study examined the SMB of bxsb females at an age subsequent to autoimmune disease onset when contrasted with younger animals yearold bxsb females showed good learning behavior with no differences in lashley maze learning and remarkably good performance in a visual discrimination learning task these results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in lashley maze learning animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures these findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals | 17|28|33|126 | systemic|neurons|cortex|behavior |
we have devised a method behavioral waveform display analysis to analyze complex ethological information by measuring SMB in real time and visualizing it as a timedependent multistate waveform to facilitate the generation and statistical analysis of behavioral waveform displays we have designed a simple macintoshbased software program when keystrokes coded to particular behavioral states are entered in real time this software measures and collates the time frequency and duration of each behavioral state these data can then be displayed either in a tabular format for statistical analysis of behavioral duration and frequency or as graphical coordinates for creating waveform displays by direct importing into graphing programs an illustration of the use of waveform display analysis to detect anomalous behaviors in cocaine and amphetaminetreated mice some of which are not detectable by a standard timesampling assay is shown both waveform display and timesampling analysis detected druginduced changes in sniffing bar hanging digging and rearing however unlike timesampling analysis waveform display analysis also detected changes in the total duration frequency and average duration of these behaviors as well as additional changes in gnawing and locomotion additionally visual scanning of behavioral waveform displays detected druginduced changes in the patterns of SMB not detectable by timesampling including a staged progression to a limited behavioral repertoire consisting of sniffing locomotion and rearing rapid switching between these remaining few behaviors a delayed ON of postinjection rearing relative to sniffing and locomotion and the absence of other transient stereotypies during the ON of drug action these data indicate that behavioral waveform display provides an approach for the detection visualization and statistical analysis of aspects of complex behavior not amenable to detection by timesampling methods | 16|197|226|244 | behavior|behavior|onset|onset |
this study investigated the effects of ingestion of a meal compared to a sham feeding on objectively measured sleepiness it was hypothesized that the ingestion of a solid meal would produce significantly greater PP sleepiness evidenced by shorter sleep onset latencies sol when compared to a SF eleven men and eight women without evidence of gastrointestinal disease or sleep disorders participated in the day study subjects underwent a premeal baseline nap at hours and were given a standardized meal at hours on one study day subjects consumed the entire meal whereas on another study day they were asked to chew and then expectorate the meal naps with PSG monitoring followed at and hours sleep onset latencies were determined by standard polysomnographic measures statistical analyses revealed the sleep onset latencies for the two meal conditions differed significantly at the hours postprandial nap only individuals demonstrated a transient decrease in SL after consuming a meal compared to a sham feeding these results lend support to the existence of a gastrointestinal effect on postprandial sleepiness | 33|46|107|148 | postprandial|sham feeding|polysomnographic|sleep latency |
mice of the cxb RI ri panel were phenotyped for period of locomotor activity in continuous dark tau and in continuous lux light taull there were significant differences in the effect of light on period delta tau taulltau among cxb ri strains and their progenitors by comparing CS means for delta tau in the cxb ri strains with typed genetic loci using a product moment correlation it was possible to hypothesize quantitative trait loci qtl important to the genetic variance in the effect of constant lowlevel light on circadian period some of the candidate genes linked to statistically associated markers are neuropharmacologically interesting provisional qtl for delta tau were found on proximal chromosome and mid chromosome in regions near qtl identified in a similar analysis of the bxd ri panel this provides additional evidence for the importance of loci on chromosomes and | 4|47 | recombinant inbred|strain |
smoking cessation often results in weight gain but certain subtypes of smokers may be more likely than others to gain weight women high in dietary restraint restrainers increase FI and gain more weight than nonrestrainers during smoking cessation restrainers have also been reported to increase food NI following laboratory stressors therefore the present study was designed to measure the influence of stress on food intake and subjective distress during acute smoking abstinence in restrained and nonrestrained women participants were women years old comprising six groups n per group in a x x design groups consisted of two levels of restraint restrained and nonrestrained and three levels of smoking ad lib sm abstinent smokers and nonsmokers whereas the withinparticipant manipulation involved two sessions differing in stress AS and control snack foods were available for consumption results showed that distress measured by the stressarousal checklist and visual analogue measures of tension and anxiety was higher in the stress session for all groups except for restrainers who smoked AL furthermore distress was significantly higher in smokeabstinent restrainers during the stress session than all other conditions however despite differences in distress no effect was observed for food intake desire for a cigarette showed a sharper increase over the stress session for restrainers compared with nonrestrainers but did not differ in the control session these data suggest that restrainers may use smoking to reduce distress and may increase smoking but not eating during AS | 28|46|110|125|165|238 | food intake|intake|smokers|stress|ad lib|stress |
anterodorsal thalami nuclei adtn exert an inhibitory influence on the hypophysoadrenal system has under basal and acute AS conditions however after chronic stress the effect is different the response to CIS imo forced immobilization for minday for days and variable chronic stress v day exposure to different stressors per day of plasma acth and corticosterone c in rats with anterodorsal thalami nuclei lesions was studied in shamlesioned rats chronic immobilization stress and VL chronic stress induced a significant increase in plasma acth and c and a reduction of adrenal c content T3 SE of lesioned rats to chronic immobilization AS there was a decrease of plasma acth compared to that in unstressed lesioned rats in contrast there was significant increase in acth levels after VL chronic AS this increase being smaller than the variable increase elicited in shamlesioned rats in all stressed lesioned animals plasma c remained unchanged however adrenal c content decreased significantly compared to that in unstressed lesioned rats these findings demonstrate that anterodorsal thalami nuclei lesions attenuated the hypophysoadrenal system response to chronic AS these data are in contrast to those obtained in previous studies under basal and acute stress conditions the reason for this discrepancy is at present unknown and its elucidation will require further studies | 17|30|72|91|92|99|124|126|176 | stress|chronic immobilization stress|variable|after|exposure|stress|variable|stress|stress |
the purpose of this study was to examine the effects of ethanol on operant responding in rats drugs may affect response rates by several mechanisms including altering motor performance or sensitivity to reinforcement these two processes can be dissociated by applying a quantitative MM of reinforced responding the responsestrength equation to response rates obtained during multiple variableinterval vi schedules of reinforcement this equation has two fitted parameters one k is thought to measure changes in motor performance and the other re is thought to measure changes in reinforcement efficacy in experimental sessions rats earned sucrose reinforcement on a sevencomponent multiple vi operant schedule the average intervals varied from to s and provided reinforcement rates from to h following stable baseline performance rats were injected intraperitoneally prior to sessions with different doses of ethanol and gkg low to moderate doses of ethanol and gkg significantly decreased response rates on several of the vi schedules but did not alter either of the fitted parameters suggesting that these doses of ethanol did not affect motor performance or sensitivity to reinforcement the gkg dose decreased responding maintained by many of the vi schedules and significantly increased the re parameter suggesting that the sucrose became relatively less efficacious in ethanol compared to vehicle sessions this relatively high dose of ethanol however did not alter responding maintained by the richest reinforcement schedule and it did not affect motor performance as defined by the k parameter these results suggest that within this paradigm ethanol affects motivation to respond rather than ability to respond | 43 | model |
most histories of senile dementia commence with alois alzheimers description in of the first case of alzheimers disease yet the history of senile dementia before is quite rich dating back to the ancient greek and roman philosophers and physicians over the years since ancient times the concept of senile PSD has evolved from a rather vague notion that mental decline occurred inevitably in old age to become defined today by a distinct set of clinical and pathological features with the potential for treatment and prevention within grasp throughout PH many elderly individuals with unpredictable SMB were sequestered in institutions and the line between mental disorders and senile PSD was hazy at best the identification of alzheimers disease at the onset of the th century was a turning point for the understanding of senile PSD and the concepts and histological findings presented by the early researchers of alzheimers disease remain relevant still today indeed these early findings are proving to be a continuing source of insight as many of the issues debated at the turn of the century remain unresolved still today this paper thus traces the history of the evolution of our current conceptualization of alzheimers disease from the amorphous grecoroman concept of ageassociated dementia | 49|88|94|107|133 | dementia|history|behavior|dementia|dementia |
increased cytokinemediated cytotoxic A-NK nk cell activity has recently been demonstrated in patients with senile dementia of the alzheimers type sdat in the present study we evaluated whether proteinkinase c pkc a main regulatory enzyme involved in the mechanism of exocytosis by nk cells has a role in the cytotoxic response of nk cells during il and ifnbeta SE from sdat patients our data demonstrate the presence of an increased cytotoxic response by nk cells to il mean increase and ifnbeta mean increase in sdat patients in comparison with healthy elderly subjects and for il and ifnbeta respectively a smaller suppression of nk cytotoxicity after cortisol was also observed in sdat mean decrease than in the control group the nk cell activity of sdat patients was inversely correlated with the cognitive status as evaluated by the analysis of mmse mini mental state examination score a comparison of young and elderly healthy subjects revealed no variations in nk cell activity a physiological decrease in cytosolic pkc activity was demonstrated in healthy old subjects T3 il and ifnbeta incubation but not in sdat patients while no variations in kinase activity were observed after cortisol incubation the decreased activity with cytokines was associated with reduced levels of pkc alpha and betaii isoforms an alteration in cytokinemediated nk cell activity associated with pkc dysregulation is therefore suggested to occur in patients with sdat these changes may indicate the existence of an immunological component to the pathogenesis and progression of the disease | 3|58|172 | natural killer|exposure|after |
alzheimers disease ad brains display intense microglial immunoreactivity in the area of senile plaques suggesting that amyloid betaprotein may stimulate microglial infiltration the activated microglia may modulate an immune response in the brain nonsteroidal antiinflammatory drugs nsaids are candidate therapeutics for ad because their effects on immune system components may influence the course of the disease the present study examined the effects of an nsaid indomethacin on amyloid betaproteininduced microglial infiltration amyloid betaprotein was chronically infused into rat lateral ventricles for weeks extracellular amyloid betaprotein deposited along the lining and diffused into the tissue surrounding the lateral ventricle immunocytochemical IF showed that animals receiving amyloid betaprotein exhibited dramatic microglial response when compared to vehicleinfused rats activated microglia surrounded immunopositive amyloid betaprotein deposits but this response was significantly attenuated in animals receiving either concurrent icv or subcutaneous sc treatment with indomethacin these results suggest that chronic amyloid betaprotein infusion induces the proliferation of activated microglia and that indomethacin may be an ERP treatment for inhibiting microglial proliferation | 99|160 | staining|effective |
the frequency of autoantibodies aabs was surveyed in several neurodegenerative diseases other neurological diseases and controls using antigenspecific eias for NF-M heavy subunit tubulin glial fibrillary acidic protein s protein tau betaamyloid peptide myelin basic protein and heparan sulfate proteoglycan HF of sera and cerebrospinal fluid tubulin aabs were found in alzheimer disease and respectively parkinson disease and amyotrophic lateral sclerosis and and in sera from multiple sclerosis and optic neuritis guillainbarré syndrome and V1 PSD high frequencies of neurofilament heavy subunit aabs were detected in guillainbarré syndrome chronic peripheral neuropathy and optic neuritis whereas some alzheimers disease and vascular PSD patients had glial fibrillary acidic protein aabs lower frequencies of other aabs were found in patient CG aab results were also compared to functional assessment of bloodbrain barrier integrity in parkinsons disease and alzheimers disease the relevance of these aabs to pathogenesis andor course of neurologic diseases merits further T0 with particular reference to subgrouping and prognosis | 20|40|74|75|100|117|150 | neurofilament|high frequencies|vascular|dementia|dementia|groups|study |
aged monthold male LE were assessed for deficits in spatial cognition relative to young monthold rats an in vitro autoradiography T0 was then conducted for muscarinic m sites using hafdx to assess binding in basal forebrain and brainstem areas where ACh neurons are localized the analysis of basal forebrain included the medial septaldiagonal band region that provides cholinergic innervation of the hippocampus the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus were analyzed in the brainstem a significant agerelated reduction in m binding was found in both the basal forebrain and BS only the reduction in the basal forebrain however was correlated with spatial learning impairment although the basal forebrain and brainstem ACh systems are each vulnerable in normal aging contributions to the behavioral effects of aging may be distinctive for the two systems | 3|20|40|90|111 | longevans rats|study|cholinergic|brainstem|cholinergic |
the effect of age on pilocarpineinduced expression of the immediateearly gene cfos was examined in the hippocampus and SC of longevans rats rats were treated with either pilocarpine mgkg or saline and sacrificed min following i.t. the level of cfos mrna and foslike protein expression was determined using in situ hybridization histochemistry and immunocytochemistry respectively in salinetreated animals comparable C2 of cfos mrna and foslike protein were observed in the hippocampus and cortical regions of young month and aged months rats the expression of foslike protein following pilocarpine treatment was increased however in frontal retrosplenial and cingulate cortex of aged compared to young rats in frontal and retrosplenial SC the changes in foslike protein were accompanied by changes in cfos mrna expression in contrast no age difference was detected in the hippocampus or parietal cortex of pilocarpinetreated rats these regionallyspecific age differences in response to pilocarpine administration suggest that mechanisms localized to those areas play an important role in determining the response to cholinergic stimulation mediated through postsynaptic M2 | 18|35|59|108|168 | cortex|injection|levels|cortex|muscarinic receptors |
groups of old and young rats were administered three tests of spatial learning and memory that are known to be sensitive to HPC dysfunction the RAM ram spatial nonmatchingtosample snmts and a spatial vs local cuepreference task old rats performed worse than young rats on the ram and snmts tasks on the cuepreference task young rats were biased to use spatial cues whereas old rats exhibited strong preferences for distinct local cues peripheral injections of glucose mgkg improved performance by old rats on the ram and snmts which correlated with measures of gl metabolism glucose treatment did not affect old rats performance on the cuepreference task there was evidence that glucosetreatment improved performance of young rats in the ram test but not the other tests the results extend the range of tasks on which glucoseinduced cognitive enhancement has been demonstrated in aged rats and provides further evidence that SM loss resulting from HPC dysfunction is especially amenable to gl treatment | 22|25|92|148|152|158 | hippocampal|radial arm maze|glucose|memory|hippocampal|glucose |
the effects of aging on acoustic and airpuff startle CR acoustic and airpuff startle habituation acoustic and crossmodal lightacoustic prepulse inhibition ppi and FPS fps were examined using y young ad adult ma middleaged and o old monthold fischer f rats ad rats had the highest acoustic startle reactivity with the y and ma rats showing smaller and comparable startle C2 the o rats had diminished startle reactivity with over a reduction in responding airpuff startle reactivity was comparable in the y and ad groups while the ma and o groups had and reductions in airpuff startle respectively there was an agerelated increase in airpuff startle habituation acoustic and crossmodal ppi were reduced significantly in o rats when compared to other age groups finally there were no effects of age on fps in summary these studies suggest that in fischer f rats there are ageassociated differences in startle CR startle habituation and ppi but no aging effect on fps | 9|23|60|148 | reactivity|fearpotentiated startle|levels|reactivity |
calciumbinding proteins play potentially important roles in neurogenesis and neuroprotective mechanisms some evidence exists that brain calbindindk calb is regulated by androgens in the present study calretinin calret and calb patterns were determined by western analysis in the medial basal hypothalamus mbh from male rats along with assaying plasma testosterone levels during PN development testosterone C2 were very low in and dayold animals approximately ngml increased in a stairstep fashion to Cmax at days approximately ngml then declined with increasing age to very low levels at days of age approximately ngml at and days mbh calret and calb levels were low however at day a significant twofold increased was observed thereafter in and dayold animals mbh calret and calb levels were in general comparable to dayold values these findings suggest that there is not a clear correspondence between the androgen status in male rats and the calciumbinding proteins calret calb expressed in the mbh therefore it appears that BB calret and calb are regulated in a developmental fashion with significant increases in expression occurring around the th postnatal week | 52|55|71|158 | postnatal|levels|peak levels|brain |
in this study we tested the hypothesis that the efficacy of lglutamate to stimulate hmk binding to the nmda receptorchannel complex is altered as a CF of aging lglutamate or related excitatory CAA eaa is the endogenous neurotransmitter of the nmda receptorchannel complex these studies examined the efficacy and potency with which lglutamate produces receptor activation channel opening and subsequent mk IB as a function of increasing age by comparing DR curves ec and emax from and monthold f rats the number of nmda receptors as determined by hmk binding in the presence of a saturating concentration of lglutamate was reduced in the inner frontal cortex entorhinal SC and the lateral striatum in aged rats when compared with young adults when a range of lglutamate concentrations were used differences in emax were noted in the same brain regions in addition to several others in aged and middleaged animals when compared with youngadult animals no changes in ec values were noted in any of the BB regions at either age when compared with youngadults | 25|32|61|70|107|164 | function|amino acid|binding|doseresponse|cortex|brain |
crosssectional studies on adult human autopsy material have shown that younger cohorts have heavier brains than older groups we sought to determine whether a similar pattern is present in the rhesus monkey a species that serves as a useful model of human brain and cognitive aging data were obtained from necropsies of rhesus monkeys females males of ages covering the entire adult lifespan of this species in addition to fresh brain weight variables considered were age sex body weight HW identity of the prosector and circumstance of death initial bivariate analyses revealed a significant sex difference in brain weight mean for males g for females g p as well as significant correlations of brain weight with body weight r p for females r p for males and heart weight r p for females r p for males identity of prosector circumstance of death and age were not significantly related to BB weight in bivariate analyses multiple LR controlling for possible confounding effects of body weight and sex also suggested that brain weight is stable throughout adulthood in the rhesus monkey | 79|150|156 | heart weight|brain|linear regression |
we determined whether FR or the drugs nimodipine ca antagonist and deprenyl a maob inhibitor prevent the OD of stroke in the spontaneously hypertensive strokeprone rat shrsp forty male shrsp rats in the age of weeks were exposed to various treatments during a period of weeks survival and blood pressure were followed in the control and deprenyl group the blood pressure values remained unchanged had died T3 weeks all rats that were treated with nimodipine survived after food restriction rats survived and showed a lower blood pressure this T0 in shrpr rats shows the superiority of nimodipine on survival and the potential of food restriction as a strokepreventing measure | 3|17|66|88 | food restriction|development|after|study |
rabbits of two age CG young months n and aging months n were implanted with chronic recording electrodes in area ca of dorsal hippocampus and trained in a delay conditioned jaw movement cjm paradigm after previously reaching criterion in a trace cjm paradigm with the same CS stimulus and unconditioned stimulus unlike results from the trace experiment there was no significant difference in trials to behavioral criterion between the two age groups there were large but temporary differences in the magnitude of conditioningrelated hippocampal neural responses early in delay training aging rabbits hippocampal responses were significantly smaller on day of delay training than corresponding responses of young rabbits p it is important to note that neural differences were not observed on days and of delay training or at criterion performance in the prior trace conditioning these results are interpreted in terms of agerelated differences in HPC responsiveness to changes in biologically significant stimulus configurations | 4|46|145 | groups|conditioned|hippocampal |
changes in condylar mobility and radiographic changes were examined in patients joints who had nonreducing disk displacement the patients had no treatment for at least one year thirty joints in persons with no current or previous temporomandibular joint PS served as a control the clinical signs and symptoms tended to be less severe T3 one year condylar mobility increased significantly during this period although it remained somewhat limited there was no significant difference in frequency of radiographically discernible changes of the condyle between patients and controls and the patients showed minimal evidence of progressive disease | 38|53 | symptoms|after |
the purpose of this clinical followup study was to evaluate the success rate of autotransplantation of human premolars in the period between and premolars in patients were transplanted a longterm success rate of with a mean followup period of years was achieved it seems to be justified therefore in selected cases to consider the possibility of autotransplantation as a good alternative to orthodontic or prosthetic treatment including implant IS when closing a gap in the dental arch | 68 | insertion |
a retrospective T0 was undertaken to analyse the etiology site and treatment procedures of pathological fractures of the mandible fifty percent of the fractures had an inflammatory cause the remaining cases were associated with severe atrophy of edentulous mandibles benign tumours cysts and primary or secondary malignancies regardless of the cause the majority of the fractures occurred in the body of the mandible pathological fractures of the mandible most often have to be treated by eliminating the cause of the underlying condition while immobilizing the fragments either with osteosynthesis or archbars and intermaxillary fixation | 2 | study |
controversies still exist about the preferred treatment of condylar head and neck fractures newly developed access techniques in combination with new methods to fix the fragments lead to satisfactory results this T0 deals with a refinement of surgical treatment of intracapsular fractures | 31 | study |
ocular signs and symptoms associated with facial trauma can be a manifestation of an underlying psychiatric disorder which may exist prior to the traumatic incident or even develop as a result of the stressful traumatic experience in a psychologically vulnerable individual two such cases are presented a brief review of psychogenic ocular PS as well as suggestions for DUE and treatment are discussed | 52|58 | symptoms|evaluation |
a range of environmental and host AF has been identified to explain the etiopathogenesis of squamous cell carcinoma of the lip however the definitive pathogenic pathway remains unclear carcinogenesis does not seem to be limited to a single agent but rather to a complex multistep process of interactions between putative risk factors in this paper the currently available data regarding risk AF considered to be causally related to the onset of lip cancer are reviewed | 6|61 | factors|factors |
the antitumor effect of photodynamic therapy pdt on mouse tumors was evaluated with bromodeoxyuridine brdu immunohistochemistry brdu was injected into the mice intraperitoneally mgkg body weight immediately after injection of brdu pdt using a photosensitizing drug hematoporphyrin oligomers mgkg body weight was carried out on the EG but not on the control group brdu labeling indices lis of the tumor cells close to blood vessels and adjacent to the surrounding normal tissue were investigated in the tumor cells close to blood vessels the lis of the experimental group were significantly lower than those of the control group as for the tumor cells adjacent to the surrounding normal tissue the lis of the EG were similar to those of the control group thus the effect of pdt was significant in the tumor cells close to the blood vessels while the RT cells adjacent to the surrounding T/N resisted pdt | 46|112|139|145 | experimental group|experimental group|tumor|normal tissue |
thirtyseven samples of oral mucosa were analysed and divided histologically into groups of NM hyperplastic lesions dysplastic lesions and squamous cell carcinoma all lesions displayed some expression of cerbb but the distribution and intensity of expression varied strongly according to the differentiation the lower the epithelial differentiation of the sample the higher the expression of cerbb oncoprotein showing very strong staining in carcinoma samples this suggests that in oral carcinoma transformation might be related to cerbb interaction | 13 | normal mucosa |
a rare case is described of merkel cell carcinoma of the cheek arising in a cutaneous neurofibroma in a patient with recklinghausen NF the relevant literature is reviewed | 22 | neurofibromatosis |
a parosteal CS with lowgrade malignancy attached to the hyoid bone in a yearold man is reported the RT was considered to present a lowgrade malignancy because slight invasion into the surrounding soft tissues and rapid growth were observed four years after initial surgery he had a local recurrence to the best of our knowledge this is the first reported case of parosteal CS in this location | 2|18|63 | chondrosarcoma|tumor|chondrosarcoma |
flow cytometric analysis of cell cycle fractions and dna ploidy was performed on biopsy specimens of oral leukoplakia the aneuploidy rate of these leukoplakias was and the mean DI of the aneuploid lesions was the aneuploidy rate was significantly higher in severely dysplastic lesions than in mildly dysplastic p and nondysplastic p lesions no significant differences in the percentages of each cell cycle fraction were seen between the diploid and the aneuploid leukoplakias however the sphase fraction of the severely dysplastic lesions among the diploid leukoplakias was higher than those of the mildly dysplastic and nondysplastic lesions and the difference between the severely dysplastic and the mildly dysplastic lesions was statistically significant p these results suggest that flow cytometric analysis of cell cycle fractions and dna ploidy might offer additional information for assessing the malignant potential of oral leukoplakias | 28 | dna index |
salivary calculi are frequently formed in the submandibular duct the most common sites are where the duct turns round the distal edge of the mylohyoid where the duct crosses the lingual nerve and just distal to the duct orifice UT calculi can cause one and glandular atrophy and then may exfoliate through the floor of the mouth an unusual case of cutaneous exfoliation of a salivary gland stone is presented the importance of early diagnosis and treatment of sialolithiasis are discussed | 39|43 | untreated|obstruction |
a discshaped bone graft was harvested from the calvarium in ten rabbits and anchored as an onlay bone graft using a titanium implant at the PTM the contralateral tibia served as the control where an implant was placed without a graft with the implant head at a height corresponding to the thickness of the graft on the test side resonance frequency measurements were performed and weeks postoperatively and removal torque measurements were performed at weeks a statistically significant higher implant stability as assessed by resonance frequency measurements rfm was measured from weeks throughout the week period the mean peak removal torque for the test implants was ncm and ncm for the control implants which was a statistically significant difference histologically the grafted bone was well incorporated and morphometry revealed more bone around the test implants calculations of shear stresses indicated that the grafted bone had similar biomechanical properties to the cortical bone of the recipient site it is concluded that the integration of titanium implants in autogenous onlay bone grafts results in an increased biomechanical support of the implant the use of rfm may also serve as a useful instrument for noninvasive monitoring of implant stability in vivo | 25 | proximal tibial metaphysis |
the in vitro differentiation of trypanosoma brucei from bloodstream to procyclic insect forms is accompanied by diminishing variant surface glycoprotein vsg and increasing levels of procyclin and phosphoenolpyruvate carboxykinase pepck in this study we examined the fate of several glycolytic enzymes of t brucei during differentiation we observed a downregulation of glycosomal phosphoglycerate kinase gpgk during differentiation in contrast intracellular levels of glycosomal G3P dehydrogenase ggapdh aldolase ald and PGI pgi remained unchanged during differentiation and apparently continued to be synthesized in the procyclic form to determine the potential role of proteasomes and other proteases during the differentiation process we tested the effect of lactacystin a specific inhibitor of proteasome activity and morpholinoureaphehomophebenzalphapyrone p a selective inhibitor of cysteine proteases on the in vitro differentiation of t brucei cells differentiated normally in the presence of microm lactacystin which confirmed our previous observation that this differentiation does not require crossing any phase boundaries in the cell cycle mutomba and wang mol biochem parasitol but the cells thus differentiated did not increase in number and retained gpgk cells differentiated under microm p also proceeded at a normal rate but failed to multiply and retained gpgk however most of the differentiated cells under microm p also retained vsg on the cell membrane surface and expressed higher C2 of procyclin suggesting that a cysteine proteases may be involved in releasing vsg and partially reducing procyclin during differentiation this cysteine PRs has been tentatively identified in the procyclic cells as a kda protein through labeling of cysteine PRs with a biotinylated p homolog k morpholinoureaphehomophevinylsulfone | 63|69|213|235|252 | glyceraldehydephosphate|phosphoglucoisomerase|levels|proteases|proteases |