bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adsorption of Fibrinogen and Fragment D of Fibrinogen onto the Insolubilized αChain of Fibrin
Authors: Matthias F R 
Published: July 2018

SummaryAfter thrombin treatment insolubilized fibrinmonomer, which is obtained from insolubilized fibrinogen covalently bound to agarose, adsorbs soluble fibrin and its derivatives from solutions. The immobilized proteins are attached to the agarose by the ‘A’ αchain. After reduction of the disulfide bridges the β and γchains can be removed from the agarose.After thrombin treatment the immobilized αchain adsorbs fibrinogen and fragment D. To some extent the β and γchain do not seem necessary for the adsorption. The amount adsorbed increases, when thrombin treatment of the insolubilized protein follows the reduction process.This may indicate that the fibrinopeptides ‘A’ of the insolubilized αchain are better accessible after the removal of the β and γchains.
Separation of Plasminogen Activators from Human Uterine Tissue and a Comparison with Activators from Human Urine and Porcine Tissue
Authors: Kok Preben 
Published: July 2018

SummaryThree types of plasminogen activator could be distinguished in extracts from human uterine tissue. The activators differed in thermostability or in mode of inhibition by EACA.All the extracts contained stable as well as labile activators. The saline extracts were uniformly inhibited by increasing concentrations of EACA. Extracts made with 2 M ammonium thiocyanate were either uniformly inhibited by EACA or showed deflections indicating contamination with an activator, which was inhibited in a biphasic manner. It was possible to distinguish between: (1) An activator, abundantly present in the tissue, which was uniformly inhibited and stable. (2) Another uniformly inhibited activator, which was labile. (3) An activator, inhibited in a biphasic manner, similar to urokinase, which was present in varying amounts in uteri with the endometrium in the proliferative phase.Gel filtration of the uterine extracts showed two major activity peaks corresponding to particle sizes of 60,000 dalton and about 10,000 dalton.Antiserum to purified plasminogen activator, prepared from porcine ovaries, inhibited the activity of the human uterine extracts, but not the activities of human urokinase or urine. Urokinase antiserum in a concentration completely inhibiting human urine or urokinase, inhibited only 10% or less of the activities of human uterine extracts.
Influence of Moderate and Strenuous Daily Physical Activity on Fibrinolytic Activity of Blood: Possibility of Plasminogen Activator Stores Depletion
Authors: Keber Dušan , Stegnar Mojca , Keber Irena , Accetto Bojan 
Published: July 2018

SummaryFibrinolysis was studied in 10 alpinists during regular physical activity of different intensity. Blood was sampled at rest and after exposure to submaximal workload on the treadmill on three occasions: before and after 6 months physical conditioning (moderate physical activity), and after 6 weeks of an alpinistic expedition (strenuous physical activity). Measurements included submaximal working capacity, fibrinogen, euglobulin clot lysis time (ELT), whole plasma clot lysis time, and estimations derived from ELT - percent increase in fibrinolytic activity after exercise (RFS), and absolute increase in fibrinolytic activity after exercise (PAR).Regular moderate activity increased the resting level of ELT, but strenuous activity decreased is. After each treadmill testing, a marked increase in fibrinolytic activity was observed. RFS was unaltered at all three testings. PAR increased after moderate activity, but decreased after strenuous activity.The results indicate that regular physical activity can lead from enhanced to decreased resting activity of plasminogen activator in blood. It is presumed that increased release of activator during prolonged stress causes partial depletion of endothelial stores with the consequence of decreased activator activity in the blood.
Molecular Study of Glanzmann Thrombasthenia in 3 Patients Issued from 2 Different Families
Authors: Vinciguerra C , Trzeciak M C , Philippe N , Frappaz D , Reynaud J , Dechavanne M , Negrier C 
Published: July 2018

SummaryIn an effort to further understand Glanzmann thrombasthenia (GT) 3 patients from 2 different families were studied. After biochemical and immunological analysis these patients were classified as type I. We observed in the first family a new restriction site for Stu I in exon II of the glycoprotein (GP) Ilia gene caused by a homozygous nonsense mutation: 62 Arg to stop codon. The parents were heterozygotes for this mutation. We found in the second family a previously described nonsense mutation: 584 Arg to stop codon in exon 17 of the GPIIb gene. The father and his two affected sons were heterozygous for this genetic defect. This mutation 62 Arg to stop codon is a new description of a genetic defect associated with GT. Furthermore, the discovery of the same mutation in 3 affected families from different ethnic groups raises the possibility of either a hot spot mutation in the CG dinucleotide region of GPIIb gene, or an ancient mutant allele present in diffuse populations at a relatively high frequency
Fibrin D-Dimer, Haemostatic Factors and Peripheral Arterial Disease
Authors: Lee Amanda J , Fowkes F Gerald R , Lowe Gordon D O , Rumley Ann 
Published: July 2018

SummarySeveral haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p ≤0.01) and vWF showed a similar pattern in men only (p ≤0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p ≤0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p ≤0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.
Environmental and Genetic Factors in Relation to Elevated Circulating Levels of Plasminogen Activator Inhibitor-1 in Caucasian Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Mansfield Michael W , Stickland Max H , Grant Peter J 
Published: July 2018

SummaryTo investigate the interaction of metabolic and genetic factors in relation to PAI-1, genotype was determined at a 4G/5G polymorphism in the PAI-1 gene promoter and at a Hind III RFLP of the PAI-1 gene in 189 Caucasian NIDDM patients. PAI-1 levels were equivalent in each genotype group and PAI-1 activity correlated with fasting insulin (r = 0.45), triglyceride (r = 0.39) body mass index (r = 0.44), cholesterol (r = 0.17) and glucose (r = 0.15). The regression slope (B) of PAI-1 activity on triglycerides was steeper in the 4G/4G group than the other two groups: 4G/4G B = 0.91, r = 0.62; 4G/5G B = 0.36, r = 0.27; 5G/5G B = 0.31, r = 0.29 (difference between slopes p = 0.02) and the association between PAI-1 activity and glucose remained only in the 4G/4G group (r = 0.35). These results confirm the association of PAI-1 levels with the features of insulin resistance and indicate that the association between PAI-1 levels and both triglyceride and glucose is influenced by genotype in the region of the PAI-1 gene promoter.
Plasminogen Activator Inhibitor-1 mRNA Is Induced by Hemorrhage in Endothelial and/Mesothelial Cells of the Rat Liver
Authors: Yamashita Masatomo , Darlington Daniel N , Imafuku Shiqichi , Gann Dionald S 
Published: July 2018

SummaryWe have recently shown that plasminogen activator inhibitor-1 (PAI-I) mRNA is elevated after hemorrhage in various tissues including liver. In this study, we set out to identify the cell types in the liver that are responsible for the increase in PAH mRNA after hemorrhage using in situ reverse transcription-polymerase chain reaction (in situ RT-PCR). Male Sprague-Dawley rats were cannulated and subjected to a 20 ml/kg hemorrhage within 3 min or 300 μg/kg of endotoxin. Pour hours later, the livers were harvested, fixed, frozen, and sectioned. RT-PCR showed an increase of PAI-I mRNA in liver 4 h after hemorrhage or endotoxin-treatment. Standard in situ hybridization could not detect PAI-I mRNA in the livers of either the hemorrhage, endotoxin, or control groups. However, in situ RT-PCR detected PAI-1 mRNA in vascular endothelial cells and capsular mesothelial cells, but not in hepatocytes, in both the hemorrhage and endotoxin groups. No signal was found in the control rats, or when the experimental protocol was modified to 1) omit the RT step, 2) precede the RT step with RNA digestion, or 3) use an irrelevant probe. These results demonstrate that hemorrhage induces PAI-1 mRNA in endothelial and mesothelial cells of liver.
Plasminogen Activator Inhibitor-1 (PAI-1) Promoter Polymorphism and Coronary Artery Disease in Non-Insulin-Dependent Diabetes
Authors: Mansfield Michael W , Stickland Max H , Grant Peter J 
Published: July 2018

SummaryElevated levels of PAI-1 are found in coronary artery disease (CAD) and non-insulin-dependent diabetes (NIDDM). PAI-1 may be involved in the pathogenesis of CAD through suppression of fibrinolysis, alternatively the high levels may result from vascular damage. There is evidence that PAI-1 levels are related to genotype at a PAI-1 promoter polymorphism. Genotype at this 4G/5G polymorphism was determined in 160 NIDDM (90 males and 70 females) patients with (n = 38) or without (n = 122) clinical evidence of CAD. Levels of cholesterol were higher (6.5 vs 5.9 mM, p <0.01) and of PAI-1 tended to be higher (PAI-1 activity 23.0 vs 20.4 U/ml) with CAD. The frequency of the 4G/4G genotype was increased and the 5G/5G genotype decreased, in the group CAD compared to those without (p <0.05). These results suggest that possession of the 4G/4G PAI-1 promoter genotype is a risk factor for the development of CAD in subjects with NIDDM.
Clinical Outcome of Orthopaedic Patients with Negative Lower Limb Venography at Discharge
Authors: Agnelli Giancarlo , Ranucci Valeria , Veschi Franca , Rinonapoli Emanuele , Lupattelli Luciano , Nenci Giuseppe G 
Published: July 2018

SummaryPharmacological prophylaxis for postoperative venous thromboembolism is generally restricted to the hospital stay. A high incidence of deep vein thrombosis (DVT) and pulmonary embolism presenting after hospital discharge has been reported and thus it has been claimed that pharmacological prophylaxis should be continued after discharge. The aim of this study was to perform a prospective survey to assess the prevalence of clinically overt thromboembolic events in hip surgery patients discharged with a negative venography without further pharmacological prophylaxis. We followed-up 213 patients with negative venography at discharge (105 elective hip replacement and 108 hip fracture patients). 186 patients (87.3%) were re-examined as outpatients one to two months after discharge. Five patients reported symptoms of DVT but the diagnosis was not confirmed by objective testing. The remaining 27 patients (12.7%) were followed up through their family doctor or by telephone call; in these patients the follow-up period ranged from 60 days to 2 years. Twenty-two patients (10.3%) were still alive and reported no signs or symptoms of venous thromboembolism. Three patients (1.4%) died for reasons not correlated with venous thromboembolism. Two patients could not be traced due to geographical inaccessibility; they were still alive after 1 year according to the records of their health care district. The results of our study suggest that in hip surgery patients with negative venography the prevalence of clinically overt thromboembolic events after hospital discharge ranges from 0 to 2.2% (95% C. I.). It is conceivable that the majority of late presenting postoperative DVT actually develop during the hospital stay and become symptomatic after hospital discharge.
Flow Cytometric Detection of Activated Platelets in Pregnant Women Prior to the Development of Pre-Eclampsia
Authors: Janes Sarah L , Kyle Phillipa M , Redman Christopher , Goodall Alison H 
Published: July 2018

SummaryPre-eclampsia is a common complication of pregnancy, in which platelets may have an early pathogenetic role. In this prospective study a whole blood flow cytometric method has been used to detect circulating activated platelets in pregnant women prior to the development of pre-eclampsia. Activated platelets were identified by bound fibrinogen or by CD63 antigen expression. Of 121 healthy primiparous women studied at 28 weeks of pregnancy, 18 (15%) developed clinical pre-eclampsia six to thirteen weeks later. The platelets of these women showed increased fibrinogen binding ex vivo (5.1% platelets positive, compared with 3.4% in those who completed a normal pregnancy, p <0.02), and increased CD63 antigen expression (0.73% positive compared to 0.45%, p = 0.01). In contrast, no differences between the women with different outcomes were detected at 28 weeks in platelet counts, or plasma ß-thromboglobulin levels. These findings confirm that whole blood flow cytometry is a sensitive technique for investigating platelet activation in a clinical setting and support the hypothesis that platelets have a critical role in the pathogenesis of pre-eclampsia
Targeting of Porcine Pancreatic Phospholipase A2 to Human Platelets: Introduction of an RGD Sequence by Genetic Engineering
Authors: Bekkers A C A P A , Vuurst H van der , Willigen G van , Akkerman J W N , Verheij H M 
Published: July 2018

SummaryThe possibility to induce specific disruption of activated platelets by binding of porcine pancreatic phospholipase A2 (PLA2) was tested by constructing a set of PLA2-mutants containing an Arg-Gly-Asp (RGD) sequence. One mutant was made with RGD as part of a surface-exposed loop (RGDloop). Four mutants were made with RGD as part of a C-terminal extension: one with RGD directly coupled to the C-terminus (RGDc) and three mutants (CRSx) with x = 22,42 and 82 hydrophylic non-charged amino acids between RGD and the enzyme. All mutants retained 20-80% activity of native PLA2 and showed little binding to resting platelets. The binding of the native enzyme and RGDloop was not increased following stimulation. In contrast, the mutants RGDc and CRSx showed stimulation-dependent binding to the platelet receptor GPIIb/IIIa, since GRGDS-peptide and a monoclonal antibody against the complex interfered with binding. In α-thrombin-stimulated platelets, CRS42 and CRS82 induced about 5% hydrolysis of [3H]-arachidonic acid-labeled phospholipids. Stimulation with a combination of a-thrombin and collagen (known to expose phosphatidylserine) increased hydrolysis to 11%. Despite the membrane disruption, the cells did not leak lactate dehydrogenase. We conclude that PLA2 can be targeted to activated platelets by introducing RGD in a C-terminal extension with a minimum distance (42 amino acids) between RGD and the enzyme. However, more hydrolytic activity is required to eliminate activated platelets among a suspension of resting platelets and other blood cells.
Oxidized LDL and Reduction of the Antiaggregating Activity of Nitric Oxide Derived from Endothelial Cells
Authors: Minuz P , Lechi C , Gaino S , Bonapace S , Fontana L , Garbin U , Paluani F , Cominacini L , Zatti M , Lechi A 
Published: July 2018

SummaryOxidized LDL has been observed to induce abnormalities in endothelial function which may be relevant for the progression of atherosclerotic lesions. We studied in vitro the possible effects of oxidized LDL on the antiaggregating activity of endothelial cells, which is dependent on release of prostacyclin and nitric oxide. We used an experimental model in which cultured human endothelial cells were placed in the aggregometer in contact with human platelets, after blockade of cyclo-oxygenase by adding acetylsalicylic acid. In this way the antiaggregant effect of endothelial cells was dependent on the release of nitric oxide alone; prevention of antiaggregant activity by preincubation of endothelial cells with 300 μM L-NG-mono-methyl-arginine confirmed this. When this system was used, endothelial cells (2–7.5 X 105ml) almost completely inhibited thrombin-induced (0.02–0.08 U/ml) platelet aggregation (2 × 108 platelets/ml), measured according to Born (11.1% ±8.5 vs 68.6% ±12.6, M ± SD). This antiaggregating activity was reduced when slightly oxidized LDL 100 μg/ml (35.2% ± 14.9, p <0.001), but not native LDL 100 μg/ml (7.5% ± 7.6), was added immediately before aggregation was induced.. Incubation of endothelial cells with oxidized LDL 100 μg/ml for 1 h did not affect the antiaggregating capacity, unless oxidized LDL was present during aggregation (18.3% ± 10.2 vs 35.8% ± 9.6, p <0.02). No significant direct effect of either oxidized or native LDL on stimulated platelet aggregation was observed. Our results indicate that slightly oxidized LDL can reduce the antiaggregating properties of the endothelium, probably by interaction with NO rather than through inhibition of its synthesis.
Post-Partum Factor VIII Inhibitors
Authors: Hauser I , Schneider B , Lechner K 
Published: July 2018

SummaryIn a retrospective study 51 published cases of post-partum factor VIII inhibitors were analyzed with regard to the outcome according to treatment. The overall outcome was favorable with 97% survival at two years. The probability of complete remission (CR, absence of the inhibitor and normalization of factor VIII activity) was almost 100% at 30 months. Steroid treatment appears to be not superior to no treatment, but patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, 6-mercaptopurine) had a significantly shorter time to CR. In the absence of a randomized trial this analysis may be helpful for decision-making in women with factor VIII post-partum inhibitors. Because of the retrospective study design, conclusions have to be regarded with caution.
Antibodies to Macromolecular Platelet Factor 4-Heparin Complexes in Heparin-induced Thrombocytopenia: a Study of 44 Cases
Authors: Amiral J , Bridey F , Wolf M , Boyer-Neumann C , Fressinaud E , Vissac A M , Peynaud-Debayle E , Dreyfus M , Meyer D 
Published: July 2018

SummaryAs heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 <0.3) and 35 patients with other causes of thrombocytopenia (A492 <0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 ± 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped ≤ 100 × 109/l only at days 11–12. Surprisingly, among 41 patients under heparin for >7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.
Familial Dysfibrinogenemia and Thrombophilia
Authors: Haverkate F , Samama M 
Published: July 2018

SummaryApproximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis.To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases with both affections were collected in a study within the framework of the SSC Subcommittee on Fibrinogen of the International Society on Thrombosis and Haemostasis. Registry forms of 51 cases were received. Twenty-six cases fulfilled the (arbitrarily chosen) criteria of familial dysfibrinogenemia and of thrombosis not due to other causes. Protein C and protein S deficiency and APC resistance as a cause of thrombosis could not be excluded in probands on anticoagulants or investigated before the discovery of the assays.The prevalence of dysfibrinogenemia in patients with a history of venous thrombosis is low, i.e. 0.8%, as deduced from 9 studies in 7 countries on 2376 patients. The 26 cases fulfilling the criteria are characterized by predominantly venous thrombosis at a young age. Severe bleeding was rare and limited to bleeding post partum. Homozygosity was established in 2 cases (Marburg and Naples), hypodysfibrinogenemia (less than 1.5 mg antigen per ml) in 5 cases. A high incidence of problems related to pregnancy, in particular thrombosis post partum and spontaneous abortions was noted amongst the 15 women with thrombophilic dysfibrinogenAn association between dysfibrinogenemia and thrombophilia is indicated by studies on relatives of the 26 probands. Analysis of 187 investigated family members showed that thrombophilia affected 20 persons exclusively in the group of 99 relatives with dysfibrinogenemia, no thrombosis was reported in the group of 88 relatives without the defect. Convincing evidence for such an association became apparent for only 5 individual propositi of whom 2 or more family members had both the defect and thrombotic episodes at a young age (Caracas V, Frankfurt IV/Vlissingen, Melun, Naples and Paris V, also named Dusart).Mainly two mechanisms to explain thrombosis as a consequence of malfunctioning fibrinogen have been suggested: a) A defective binding of thrombin to abnormal fibrin which leads to increased thrombin levels (Malmö, Naples, New York I, Pamplona II, Poitiers), b) A defective stimulatory function of abnormal fibrin in the t-PA mediated fibrinolysis (Argenteuil, Chapel Hill III, Date, New York I, Nijmegen, Pamplona II, Paris V).Defects at the molecular level, elucidated in 15 out of the 26 cases fulfilling the criteria, were localised in the C-terminal part of the γ-chain (3 cases), in the N-terminal part of the Bβ-chain (3 cases) and in the Aα-chain (4 cases) of fibrinogen. Why a particular molecular defect leads to malfunction of fibrin(ogen) is still unknown.
Incidence of Factor VIII Inhibitor Development in Severe Hemophilia A Patients Treated only with One Brand of Highly Purified Plasma-Derived Concentrate
Authors: Guérois Claude , Laurian Yves , Rothschild Chantal , Parquet-Gernez Armelle , Duclos Anne-Marie , Négrier Claude , Vicariot Monique , Fimbel Béatrice , Fressinaud Edith , Fiks-Sigaud Marianne , Derlon Annie , Berthier Anne-Marie , Gaillard Solange , Bertrand Marie-Anne 
Published: July 2018

SummaryThe incidence of factor VIII inhibitor was studied in a cohort of 56 previously untreated patients with severe hemophilia A (factor VIII below 1 U/dl). They received only one brand of highly purified factor VIII concentrate (HPSD-VIII) prepared by conventional chromatography with a solvent-detergent step for viral inactivation. Followup since the first infusion of HPSD-VIII was from 1 to 76 months (mean = 29) and cumulative exposure days (CED) from 1 to over 100 (median = 26). Five patients (9%) developed an inhibitor after 6 to 19 CED, only one being a high responder (2%), showing a low incidence of inhibitor compared with previous studies using high purity plasma- derived or recombinant products.