bluuebunny/crossref_metadata_2025_split huggingface dataset:
GENERATION OF COMPLEMENT ACTIVATION PEPTIDES DURING STORAGE OF PLATELET CONCENTRATES (PC)
Authors: Bode A P , Miller D T , Newman S 
Published: August 2018

Platelets are routinely stored for transfusion at room temperature in autologous, citrated plasma. We have demonstrated previously that these conditions do not completely block activation of plasma enzyme systems, as indicated by generation of thrombin activity (Vox Sanguinis, JL1:192,1986). Here, we demonstrate the conversion of large amounts of complement factor C3 during storage of citrated PC by using radioimmunoassay quantitation of the activation peptide C3a des-Arg (Upjohn Diagnostics). Supernatant samples from stored PC and from citrated platelet-poor plasma (PPP) stored under the same conditions showed a rapid linear increase in C3a levels over time with no significant difference (paired t-test, p<0.5) between PC and PPP (see table). The values at Day 10 represent conversion of approximately 11% of the native C3. Possible effects on stored platelets of C3 conversion in the surrounding plasma include:activation of platelets by C3a des-Arg (M.Polley and R. Nachman; J.Exp.Med. 158:603, 1983) and deposition of C3b on the cell surface as "innocent bystanders" (A. Salama and C. Mueller-Eckhardt; Transfusion 25:528,1985).In contrast, <10 ng/mL C5a was found in all samples tested, representing less than 0.2%conversion of C5a.Nephelometricassay of native C5 levels in PC samples showed a slight but significant difference by a paired t-test (p=0.04) between fresh PC (mean=117 ug/mL±12.0, n=6)and P
stored for 10 days(nean=108 ug/mL±9.7). Nochange in C5 levels was observed in stored PPP (106 ug/mL to 107 ug/mL). Radiolabelled monoclonal antibodies to C3 fragments showed less than 600 molecules bound per platelet. This study demonstrates for the first time the extent of complement activation in stored platelet concentrates.
PLASMINOGEN ACTIVATOR INHIBITOR ACTIVITY IN SEPTICAEMIA
Authors: Páramo J A , Cuesta B , Hernrnández M , Fernrnández J , Paloma M J , Rocha E 
Published: August 2018

In vitro and in vivo studies have shown that endotoxin induces a marked increase in plasma plasminogen activator inhibitor (PAI) activity. Plasma PAI and endotoxin concentration (limulus lysate chromo-genic peptide substrate) were determined in 61 patients with sepsis: temperature greater than 38° and either positive blood cultures (n= 32) or negative blood cultures in neutropenic patients. Thirty age-matched healthy subjects served as control group.There was a marked increase in PAI in patients (7.1±10.5 U/ml) as compared to controls (0.9±0.8 U/ml) with statistical differences (p<0.002). Mean endotoxin concentrations in patients was 1779 pg/ml (Ref. = no detectable). PAI concentration was significantly higher in patients with positive blood cultures (p<0.009). Such an increase was higher in patients with Gram-negative bacteria (n= 26) than in those with Gram-positive bacteria (n= 6), but without statistical differences. The highest PAI concentration was found in 9 patients with disseminated intravascular coagulaition (DIC) as compared with those without DIC (p<0.002). No correlation was found between PAI and endotoxin concentrations.We conclude that there is a marked increase of PAI activity in septicaemia which may contribute to the pathogenesis of DIC-associated sepsis.
TWO ABNORMAL FIBRINOGENS DESIGNATED AS OSAKA II AND MORIOKA WITH A HITHERTO UNIDENTIFIED AMINO ACID SUBSTITUTION; γARG-275 BY CYS
Authors: Terukina S , Matsuda M , Yoshida N , Yamazumi K , Takeda Y , Takano T 
Published: August 2018

A hitherto unidentified amino acid substitution of γ Arg-275 by Cys has been found in two abnormal fibrinogens, Osaka II and Morioka. The propositi are both asymptomatic heterozygotes for the abnormality characterized by altered polymerization of fibrin monomers. Reducing SDS-PAGE revealed that fibrinogens derived from thé propositi both consist of two populations; one with a normal and the other with an abnormal longer γ-chain by 0.5 Kd.The γ-γ cross-linking took place nearly normally, however. Analyzing plasmic digests of fibrinogen by SDS-PAGE, we located the abnormality residing in the γ-chain remnant of fragment D. Chromatofocusing of D1 obtained by plasmic digestion in 5 mM Ca++ of purified fibrinogen separated the variant D1 (vD1) from the normal one (nD1) distinctly, as confirmed by SDS-PAGE and functional studies. As anticipated, vD1 failed to interfere with normal fibrin polymerization and thrombin clotting of normal fibrinogen, whereas nD1 inhibited these reactions significantly. After reduction and pyridylethylation, vD1 and nD1 were individually digested with lysylendopeptidase (lysEP). Analyzing the digests by reverse phase HPLC, we noted a single peak present in the digests of vD1 but missing in those of nD1, and vice versa. Analysis of N-terminal five cycles of these peptides suggested that both of them corresponded to the peptide with residues 274302 based on the known sequence data. Primary sequence and total amino acid analyses revealed that γ Arg-275 has been substituted by Cys in both of these abnormal fibrinogens. Analysis of the lysEP-digests of the isolated γ-chain also gave the same result. Since no free SH has been identified at the γ Cys-275 substitute, the variant γ-chain may be endowed with some additive by an S-S linkage. Even if so, elucidation of an apparent elongation by SDS-PAGE of the γ-chain variant must await further investigation. In any case, however, the substitution of γ Arg-275 by Cys may have induced critical alterations in the γ-chain-dependent polymerization site in the D domain in these two abnormal fibrinogens.
REMOVAL OF HUMAN ANTIBODIES TO FACTOR VIII :C FROM HEMOPHILIAC PLASMA USING NEW SYNTHETIC SORBENTS
Authors: Messaïkeh H , Belattar N , Gulino D , Jozefonvicz J , Sultan Y 
Published: August 2018

Human antibodies that neutralize factor VIII procoagulant activity (Anti VIII:C) detected in polytransfused patients with hemophilia A cause serious difficulties for the affected patients as they inactivate any injected FVIII preparations.We hypothesized that FVIII:C might possess active sequences composed of amino acids able to bind Anti VIII:C antibodies. Consequently, completely synthetic resins with suitable chemical substituents mimicking these sequences might interact with Anti VIII:C antibodies. Based upon this hypothesis, crosslinked polystyrene was substituted by various amino acids or their derivatives in order to obtain completely synthetic adsorbents able to remove Anti VIII:C antibodies from hemophiliac plasmas. To establish the relationship between chemical composition of the resins and their affinity towards Anti VIII:C antibodies, the "in vitro" removal of these inhibitors from hemophiliac1s immunoglobulins G was tested by measuring simultaneous adsorptions of either IgG or Anti VIII:C antibodies. Specific and accurate methods veil adapted for studying the adsorption of these two kinds of proteins were used for evaluating either the IgG concentrations (rocket iirrnunoelectrophoresis) or the Anti VIII:C concentrations (immunoradicmetric method). To determine the most suitable chemical groups able to develop a specific adsorption, a first screening on amino acid substituents was undertaken and allowed the selection of glutamic acid and hydro -xyproline. In fact, among the twenty resins tested, the most interesting one is obtained by linking glutamic dimethyl ester derivative onto the polystyrene matrix. This resin possesses a pseudo-specificity towards Anti VIII :C antibodies as it is possible to remove 12 % of Anti VIII :C antibodies and only 3 % of IgG on 5 mg of this resin. Furthermore, the hydrophobic sites on the surface seems to be involved in the Anti VIII :C adsorption as demonstrated by comparing selectivity obtained with mono and diester derivatives either in aspartic or glutamic series.
DIAGNOSIS AND MANAGEMENT OF ITP DURING THE PERINATAL PERIOD
Authors: Christiaens G C M L 
Published: August 2018

Although maternal and perinatal mortality and morbidity in pregnant patients with ITP are lower than previously assumed, they are not negligable. Significant postpartum hemorrhage occurs in 7% of the mothers with ITP. Thrombocytopenia is found in 51% of the newborns born from mothers with ITP and 6% of these have serious bleeding problems. Tests which predict which fetuses are at risk, are not yet available. Thrombocyte counts in a fetal blood sample are falsely low in 40% of cases.A prospective controlled randomized study done in the Netherlands failed to show an effect of antenatal corticosteroid treatment on neonatal platelet counts. Elective caesarean section has not been shown to protect against intracranial bleeding in thrombocytopenic newborns. The choice between vaginal delivery and caesarean section in ITP patients should be made on obstetric grounds with one exception: no other assisted vaginal delivery than the easy outlet forceps should be done. All cases of slow progress of the second stage of labour with insufficient descent should be terminated by caesarean section as well as breech delivery with suboptimal progress. Newborn thrombocyte counts should be done daily during the first week of life, since lowest platelet counts are often found between the 3rd and 5th postpartum day. Newborn thrombocytopenia is transient and does not warrant splenectomy, but can necessitate treatment with corticosteroids and/or high doses of immunoglobulin 6. Current data do not justify to dissuade breastfeeding.The recurrence of neonatal thrombocytopenia in subsequent patients is unknown.
PROPHYLACTIC EFFECT OF ARGIPIDINE (MD-805) ON DEVELOPMENT OF LESIONS IN RAT PERIPHERAL ARTERIAL OCCLUSION MODEL
Authors: Hara T , Iwamoto M , Ogawa H , Tamikawa M 
Published: August 2018

Argipidine ((2R,4R)-4-methyl-1-(N2-[(RS)-3-methyl-l,2,3,4-tetrahydroquinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylie acid hydrate) is a potent and specific inhibitor of thrombin(Ki=0.039μM). We tested the effect of argipidine on a new animal model of peripheral arterial occlusion (PA0).PA0 was prepared by injection of 5% lactic acid into rat femoral artery. Macroscopic changes of legs progressed asfollows; change to violet color around whole paw (3-24hr), edema (3-24hr), gangrene of fingers (after 24hr) and mummification of whole paw (after 7 days). Pathological examination demonstrated partial deletion of arterial endotherial cells and subsequent occlusive arterial thrombosis. Coagulo-parameters in circulating blood did not change 3 hours after lactic acid injection. To evaluate the effect of tested antithrombotic drugs, sum of lesion grade of five fingers is used as an index of severity of. PA0.Single subcutaneous injection of argipidine 30 minutes before lactic acid injection, inhibited significantly development of lesions of the lower limb at doses lOmg/kg and 30mg/kg in a dose-dependent manner. The number of rats which showed moderate or severe lesion on their legs at 14 days after lactic acid injection was decreased to 2/8 in argipidine treated (30mg/kg) rats from 7/8 in control rats. But argipidine injected simultaneously with lactic acid showed weak inhibitory effect (not significant) and argipidine injected three hours after lactic acid injection did not showany inhibitory activity. Slight prophylactic effect was also found by subcutaneous injection of heparin at a dose of 900U/kg, but its effect were not significant.In a separate experiment, PT and APTT were assayed after subcutaneous injection of argipidine or heparin. Heparin (900U/kg) prolonged APTT much greater than argipidine (30mg/kg), but as for prolongation of PT, argipidine was more effective than heparin.These results suggest that extrinsic coagulation system plays an important role in initiation of lesions of this model.
TISSUE FIBRINOLYTIC ACTIVITY:DIFFERENCES BETWEEN NORMAL AND NEOPLASTIC PULMONARY TISSUE
Authors: Doni A , Crisci C , Bartoloni Saint Omer F , Di Lollo S , Leoncini G , Rosi E 
Published: August 2018

In order to verify differences between the fibrinolytic activity in normal and neoplastic pulmonary tissue, 16 subjects underwent infra-operatory biopsy.Samples from normal lung and neoplastic tissue areas were obtained from each subject and then examined using Todd's histoehemical method (Doni A. et al.: VII International Congress on Fibrinolysis, Venezia 1984)The results were evaluated using Wilcoxon’s test, and were expressed by an Index of the Potentiality of Fibrinolysis (I.P.F.) = % Lysis area/% tissue area and by the Ratio between I.P.F. at 30’ and I.P.F. at 45’ of incubation.A statistically significant difference between I.P.F. of normal tissue and the neoplastic one at 30’ and 45’ of incubation was found while no difference between the Ratio of normal and neoplastic tissue was noted.These data suggest that differences in fibrinolytic activity exist as regards normal and neoplastic pulmonary tissue and that these differences may be related to the different amounts of plasmonogen activators (perhaps tPA) present in normal and neoplastic tissue (Doni A. et al.: VIII International Congress on Fibrinolysis, Vienna 1986).Kinetics of fibrinolysis did not show statistically significant differences
EFFECT OF DIPYRIDAMOLE ON SPONTANEOUS PLATELET AGGREGATION IN WHOLE BLOOD DECREASES WITH THE TIME AFTER VENEPUNCTURE:EVIDENCE FOR THE ROLE OF ADP
Authors: Saniabadi A R , Lowe G D O , Forbes C D 
Published: August 2018

Spontaneous platelet aggregation (SPA) was studied in human whole blood at 3,5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter (Ultra Flo 100), SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of blood at 37°C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10-5M at each time interval; (b) 0.5-100 x 10-6M at 3 and 30 minutes, and (c) 15 x 10-6M in combination with 2 x 10-4M adenosine (Ad), 8 x 10-6M 2-chloradenosine (2ClAd, a specific ADP receptor blocker) and 5 x 10-5M aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy withAd, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when an effective concentration of Dipy and an ineffective concentration of Ad (10-4M) were addedtogether, the inhibitory effect of Dipy was not increased, suggesting that Dipy inhibits platelet aggregation independent of Ad.The increase in SPA with the time after venepuncture was abolished when bloodwas taken directly into the anticoagulant containing 2ClAd (5 x 10-6M). We conclude that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture, and makes a serious contribution to the artifacts ofin vitro platelet function studies. Furthermore, the decrease in the inhibitory action of Dipy with the time after venepuncture may explain why previously, it has not been possible to observe inhibition of platelet aggregation by Dipy in platelet rich plasma which requires time to prepare.
A METHOD FOR DETERMINATION OF FUNCTIONAL α-2 ANTIPLASMIN LEVELS IN PLASMA: THE CIRCULAR LYSIS INHIBITION OF AGAROSE-FIBRIN PLATE
Authors: Avello A Garcia , Fernandez Trejo R A , Garcia Frade L J , Vigo A Pardo , Cesar J , Navarro J L 
Published: August 2018

A new, simple and reliable technique .has been developed for the determination of functional α-2 Antiplasmin in plasma; It is based on the circular inhibition of lysis produced by a-2 Antiplasmin from a hole punched out in an agarose-fibrin plate in which Urokinase has been previously dissolved.Briefly: An Agarose-Fibrin plate is made with Agarose>(l%), Fibrinogen (0.5%) and Urokinase (0.5 U/ml). The components are mixed at 422 C and thrombinCO.25 U/ml is used to coagulate Fibrinogen. The mixture is poured on a horizontal glass, plate and left at room temperature. 30 min later a series of holes are punched out in the plate and the samples and controls are seeded in the holes.The plate is incubated during 18 hours at 37° C in a humid chamber. After that time, all the plate has been lysed by plasmin produced by Urokinase except a circular area around the holes where α-2 Antiplasmin has migrated from the border: A round opaque circle can be seen around the holes and the diameters are proportional in a log-log scale with the aα-2 Antiplasmin levels of the sample.A standard curve is constructed with a pool of plasmas and the diameters of each sample are referred to it in a log-log scale, determining in this way the levels of functional α-2 Antiplasmin as a percentage.The lysis inhibition circle is entirely due_ to α-2 Antiplasmin and not to any other Fibrinolysis inhibitor: This has been demonstrated incubating previosusly the samples with antibodies directed to α-2 Macroglobulin, α-1 antitrypsin and C-l Esterase Inhibitor with no change in the circle. But when samples were incubated with an antibody to α-2 Antiplasmin, the opaque lysis inhibition circle disapeared.This method presents a very good correlation with other functional methods (cromogenic substrate s-2251 Kabi:r=0.92 p(0.01) and is comparatively simpler.the sensibility of the method is 0.5 % and the reproductibility is 3% day by day and 1% in a same day.
A NEW ONE STAGE CLOTTING ASSAY FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARINS
Authors: Giese Ch , Knodler A , Zimmermann R , Harenberg J 
Published: August 2018

Heparin and its low molecular weight (LMW) derivatives are usually measured by chromogenic or fluorogenic synthetic substrate assays and by coagulation tests. Since the activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) are insensitive to LMW heparins, we report here of data obtained with heptest, a new one stage modification of the original heparin in plasma assay of Yin.
The assay was compared with the antifactor Xa chromogenic substrate S2222 method, the TCT and aPTT tests in 100 patients receiving unfractionated pig intestinal mucosa heparin and 100 patients treated with low molecular weight heparin Kabi 2165. The results indicate a high correlation between the heptest and the anti Xa chromogenic substrate method, whereas the correlations were lower for the aPTT and TCT.
correlations with LMW heparinThe lowest detection limit of the heptest is 0,005 heparin units per ml plasma. The test is very sensitive, simple, highly reproducable and reliable clotting assay for unfractionated and low molecular weight heparins in human plasma. The test detects with high preference the inhibition on factor Xa but also the other anticoagulant effects on die coagulation tractors.
EFFECT OF ATRIAL NATRIURETIC POLYPEPTIDES ON PLATELET FUNCTION
Authors: Asaji T , Murakami E , Takekoshi N , Matsui S , Imaoka T 
Published: August 2018

Atrial natriuretic polypeptides (ANP) have been shown to possess a potent diuretic and natriuretic activity, and medicated to patients with heart insufficiency as a drug to be mediated by cGMPaccumulation in glomeruli. A existence of receptors for ANP have recently beenreported in human platelet. But, whether ANP has a direct effect on platelet function remains to be known.Single stimulation of ANP in any concentration did not induce aggregation in neither platelet rich plasma, nor washed platelets. Also no effect of pretreatment with ANP was observed against aggregation triggered by known mediators of platelet activation (Thrombin, ADP, Epinephrine, Collagen) using platelet rich plasma and washed platelets.Therefore, biochemical parameters such as cyclic nucleotides (cAMP, cGMP), phosphatidylinositol hydrolysis and protein phosphorylation, leading to the early stage of platelet activation were examined to investigate the effect of ANP in receptor linked transducing mechanism. Neither cyclic nucleotides accumulation nor [32 P] phosphatidic acid production were detected in platelets treated with ANP. ANP caused a small increase of 32P incorporation into M 30K protein, but no change on the level of phosphorylation of 47K, 20K protein (Imaoka, T. and Haslam, R.J., J.Biol.Chem.258,11404, 1983) was observed.These results clearly suggested thatANP binding with membrane receptor was not linked with adenylate cyclase, ganulate cyclase and phosphatidylinositol phosphate turnover in human platelet, maybe because of too few numbers of ANP receptor. Mechanism of 30K protein phosphorylation and Ca++ mobilization are important subjects for future study, (supported by MESC of Japan)
HEREDITARY PLATELET FUNCTION DISORDERS IN JAPAN
Authors: Yasunaga K 
Published: August 2018

Nationwide surveys of hereditary platelet function disorders in Japan were carried out in 1976, 1981, and 1986. Information on 271 cases received in the 1986 survey was analyzed with that for 103 other cases reported in earlier surveys but not in 1986, making a total of 374 cases. The mortality rate was 6.8% of 162 cases in 1976, 6.6% of 213 cases in 1981, and 5.9% of 374 cases in 1986. Bleeding symptoms appeared at age 12 years in 56.8% of patients and the most common were epistaxis and purpura. Of the 295 cases 49.5% were isolated cases, 20.3% had siblings with confirmed bleeding tendencies, and 30.2% had other kin with bleeding tendencies, suggestings autosomal tnansmission. Consanguineous marriage was reported by 11.9% of patients.Of the 374 cases in 1986, 59.4% were thrombasthenia (TA), 11.5% Bernard-Soulier symdrome (BSS), 22.5% release abnormalities (PRA), 1.3% other, and 5.3% unclassified. Of the 84 cases of PRA, 60 were storage pool deficiency, 18 release mechanism abnormalities, and 6 undecided between the two types. The resultsof laboratory tests were as follows
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PLATELET DYSFUNCTION INDUCED BY TETRAHYDROCANNABINOL
Authors: Patel R , Bick R 
Published: August 2018

Many drugs and other agents have been reported to induce platelet dysfunction and clinical bleedability; however, tetrahydrocannabinol (marijuana) has thus far not been reported. The patient herein described is a 28-year-old Caucasian female who wasreferred for evaluation of easy and spontaneous bruising. On history, the patient related that for a three-month period she had been developing spontaneous ecchymoses of the extremities and torso. She denied any medication other than heavy marijuana use. Hemostasis evaluation revealed her to have a normal prothrombin time, partial thromboplastin time (PTT), Factor VIII coagulant activity (Factor VIII:C), Factor VIII related antigen (Factor VIII:RAg), and ristocetincofactor activity. Platelet aggregation was performed which revealed abnormal aggregation to epinephrine, adenosine diphosphate (ADP) and abnormal release but normal aggregation toristocetin. She was asked to refrainfrom marijuana and was reaggregated revealing normal aggregation and release to epinephrine, ADP, collagen and arachidonic acid; however, ADP release induced by ristocetin remainedmoderately abnormal, even though aggregation was normal. In addition, with cessation of marijuana use, her clinical bruising abated.Following this, she again indulged in marijuana and she was reaggregated, revealing delayed aggregation and release to epinephrine with abnormal aggregation to ADP. Additionally, ristocetin release and adenosine triphosphate (ATP) release remained abnormal but aggregation remained normal and arachidonic acid aggregationremained normal.In summary, we herein describe a young female who demonstrated aggregation abnormalities and clinically significant spontaneous bruising during periods of using marijuana; the defect disappeared upon cessation of marijuana and reappeared upon resumption of marijuana use. The defect atpresent appears to be that of a membrane-type defect with no evidence that marijuana interferes with the prostaglandin pathway.