bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of Stable Complexes Between Urokinase and a Human Urinary Component
Authors: Cieplak Witold , Hart David A 
Published: July 2018

SummaryHuman urine was found to contain multiple species of urokinase (UK)-like plasminogen activator (PA) activity when subjected to concentration and/or dialysis and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. Untreated, freshly voided urine contained only Mr = 52,000 and 35,000 UK while dialyzed or undialyzed urine concentrates contained additional PA activity at Mr = 80,000 and 95.000. SDS-PAGE of incubation mixtures of radioiodinated UK (Mr = 52,000 or 35,000) and urine concentrates revealed the presence of radiolabeled complexes with MrS of 80,000 and 95.000. The bond(s) involved in complex formation was also relatively resistant to heat and reduction. Treatment of radioiodinated UK with the serine proteinase inhibitor, p-nitrophenyl guanidinobenzoate, prior to incubation with dialyzed, concentrated urine prevented formation of the complexes. In addition, the enzymatic activity of the Mr = 80,000 and 95,000 species was unaffected by diisopropyl fluorophosphate. These results indicate that UK forms SDS-stable complexes with a urinary component that has a Mr of approximately 40,000. The results further suggest that these complexes express PA activity when analyzed by SDS- PAGE and zymography.
Characterisation of Epitopes on Human Tissue Plasminogen Activator Recognised by a Group of Monoclonal Antibodies
Authors: MacGregor Ian R , Micklem Lisel R , James Keith , Pepper Duncan S 
Published: July 2018

SummarySeven mouse monoclonal antibodies have been produced against human melanoma tissue plasminogen activator (t-PA). They were specifically bound to 125I t-PA but not 125I urokinase (u-PA) and inhibited t-PA, but not u-PA, activity in plasminogen- rich 125I fibrin wells. Three of the antibodies directly inhibited the amidolytic activity of t-PA and the two most effective also bound near the active site histidine residue as determined by competition experiments using active site blocking agents. Several antibodies interfered with the fibrin binding properties of t-PA. One antibody neither interacted with the active site nor inhibited fibrin binding but still effectively quenched t-PA activity in fibrin wells suggesting that it masks another region of the molecule necessary for effective biological activity.
ADP Induced Depolarization of Human Platelet Membrane Potential
Authors: Wencel-Drake June D , Feinberg Harold 
Published: July 2018

SummaryThe transmembrane potential of human blood platelets suspended in plasma was investigated by studying the distribution of a radiolabeled permeant ion [14C] thiocyanate. The membrane potential of resting platelets was found to be -54.50 mV ± 9.23 S.D. with a range of -39 to -76 mV (n = 27). The possibility that platelet activation alters membrane potential or that changes in membrane potential serve as an activation trigger was investigated. Stimulation by ADP (10 ¼M) resulted in a significant (p :0.05) depolarization of the membrane potential. Preincubation with 6 mM EGTA failed to inhibit ADP-induced depolarization even though EGTA effectively prevented primary and secondary aggregation but not shape change. Preincubation with PGE1 inhibited shape change, aggregation, and the ADP- induced depolarization. No significant change in membrane potential was observed following stimulation by epinephrine (50 ¼M). These results suggest that the initial interaction of ADP and its receptor may involve an inward positive current which can be determined by thiocyanate distribution.
Measurement of Autoantibodies Against Fibrinogen and Fibrin Degradation Products by Enzyme-Linked Immunoassay
Authors: Whitaker A N , McFarlane J R , Rowe E A , Lee K , Masci P P 
Published: July 2018

SummaryWe have devised a simple enzyme immunoassay to detect and quantitate autoantibodies against derivatives of fibrinogen. This assay has been applied with a range of antigens including a fibrinogen lysate (containing X, Y, D and E), D dimer, D dimerE and a preparation of high molecular weight complexes derived from crosslinked fibrin. We have found that autoantibodies interacting with these antigens can be detected in varying concentrations in most sera from both normal subjects and patients with a variety of diseases and are evidently of mixed Ig class. These autoantibodies are directed against at least several cryptic antigens which appear during fibrinogen/fibrin degradation and some appear to be directed specifically against cross- linked fibrin derivatives. No clear disease correlates have yet emerged but a relationship between elevated levels and prior infective, thrombotic, inflammatory or traumatic disorders is likely. It is suggested that these autoantibodies may contribute to the catabolism of fibrinogen derivatives, provide a marker of thrombosis, and sometimes produce pathologic effects.
Maternal and Fetal Platelet Responses and Adrenoceptor Binding Characteristics
Authors: Jones C R , McCabe R , Hamilton C A , Reid J L 
Published: July 2018

SummaryPaired blood samples were obtained from mothers (venous) and babies (cord venous blood) at the time of delivery by caesarean section under epidural anaesthetic. Fetal platelets failed to aggregate in response to adrenaline in vitro although adrenaline could potentiate the threshold response to adenosine diphosphate (1 μM). Fetal platelet responses to collagen and 8 Arg vasopressin did not differ significantly from maternal responses. Maternal and fetal platelets also showed similar inhibition of aggregation after activation of adenylate cyclase (PGE1 and parathormone), in contrast to the inhibition of adenylate cyclase by adrenaline.Alpha2 adrenoceptors were investigated using [3H] yohimbine binding receptor number and were reduced modestly but significantly on fetal compared to maternal platelets. The failure of fetal platelet aggregation in response to adrenaline appears to be related to a failure of receptor coupling and may represent a delayed maturation of fetal platelet alpha receptors or a response- to increased circulating catecholamines during birth.
Measurement of Fibrinogen Concentrations in Suspensions of Washed Rabbit and Human Platelets by Radioimmunoassays
Authors: Harfenist Elizabeth J , Wrana Jeffrey L , Packham Marian A , Mustard J Fraser 
Published: July 2018

SummaryAlthough fibrinogen is a cofactor in platelet aggregation, washed rabbit platelets aggregate when stimulated with ADP even when no fibrinogen is added to the platelet suspension. Washed human platelets usually do not aggregate to a significant extent when stimulated with ADP unless fibrinogen is added. To study this phenomenon, radioimmunoassays for rabbit and human fibrinogens have been developed and used to measure fibrinogen concentrations in suspensions of washed platelets. The fibrinogen concentration in the suspending medium of rabbit platelets was 2.5 ± 0.9 μg/109 platelets, and upon stimulation with 9 μM ADP it increased to 10.7 ± 2.9 μg/109 platelets. The loss of fibrinogen from the platelets was significantly greater than the loss of 14C-serotonin (11% vs 2%). The presence of prostaglandin E1 reduced the fibrinogen concentration to approximately 1 μg/109 platelets and prevented aggregation and loss of fibrinogen when the platelets were stimulated with ADP. With human platelets, the extracellular concentrations of fibrinogen and β-thromboglobulin, expressed as percentages of the amount in the platelets, were similar, and the increase in fibrinogen concentration upon ADP stimulation (approximately 2%) was much lower than with rabbit platelets. We conclude that rabbit platelets may release fibrinogen from their α-granules when stimulated with ADP, and that a portion of the released fibrinogen becomes available to support aggregation. Smaller amounts of fibrinogen would become available in the case of human platelets.
A Comparison of Heparin Potency Estimates Obtained by Activated Partial Thromboplastin Time and British Pharmacopoeial Assays
Authors: Merton R E , Curtis A D , Thomas D P 
Published: July 2018

SummaryHeparin samples from five manufacturers were assayed by the revised British Pharmacopoeia (BP) heparin assay and the results compared with those obtained using the activated partial thromboplastin time (APTT) assay. The United States Pharmacopeia (USP) reference heparin preparation and the 4th International Standard (IS) for heparin were also assayed by the two methods relative to the 3rd IS. The results obtained by the revised BP assay were in close agreement with those obtained by the APTT assay for all the heparins that were tested. The assays revealed that there is at least a 10% discrepancy between the International Unit for heparin and the USP unit.
The Effect of Diabetes Regulation on Platelet Release, Fibrinolysis and Coagulation Tests, Before and After Stimulation with DDAVP
Authors: Knaap J H v d , Boer A C de , Pannebakker M A G , Heerde W van , Ottolander G J H den 
Published: July 2018

SummaryIn this longitudinal study we measured β-TG, PF4, fibrinolytic activity (extrinsic and euglobulin fraction), fibrinogen, FVIII RAg and FVIII Rcof before and after i.v. DDAVP (FPA was only measured before DDAVP) in 20 patients with diabetes mellitus. These parameters were measured on three occasions: phase I: during disregulation, phase II: after three weeks of strict control, phase III: after nine weeks of good control. Twenty-two healthy volunteers served as normal controls.No significant differences related to metabolic control were found for β-TG, PF4, FPA and fibrinogen. There was no change after i.v. DDAVP administration. Fibrinolytic activity showed a significant increase after i.v. DDAVP. Baseline values and post-DDAVP increase were not significantly different from our normal controls.FVIII RAg and FVIII Rcof were both significantly elevated in diabetes mellitus. Both increased significantly after DDAVP. The FVIII RAg release (ΔFVIII RAg) was significantly less in the diabetics. Fibrinolytic activity, FVIII RAg and FVIII Rcof are independent of the degree of metabolic control in patients with diabetes.
Purification of a Specific Placental Plasminogen Activator Inhibitor by Monoclonal Antibody and Its Complex Formation with Plasminogen Activator
Authors: Åstedt B , Lecander Ingegerd , Brodin T , Lundblad A , Löw Karin 
Published: July 2018

SummaryA monoclonal antibody of IgG2a-type was obtained against a specific fast acting plasminogen activator inhibitor found in placenta. The placental inhibitor was purified by affinity chromatography using the monoclonal antibody and additionally in a FPLC-system. A strong complex formation was found between the inhibitor and urokinase and also with the two-chain form of plasminogen activator of the tissue-type. A weaker complex was found between the placental inhibitor and the one- chain form of the tissue-type activator.
Changes in Plasminogen Activator Activity and Plasmin Inhibition in the Pig During Experimental Hypovolaemia
Authors: Smokovitis A , Wagner M , Starlinger M , Opitz A , Binder B R 
Published: July 2018

SummaryA markedly decreased plasminogen activator activity (PAA) was seen in lung, heart and kidney after experimental hypovolemia in the pig. In 2 of 12 cases, an increased PAA was found in liver and spleen. In skeletal muscle, skin, sciatic nerve and in 10 of 12 cases in liver and spleen PAA was unchanged. A slightly increased plasmin inhibition was noted only in the lung. These changes in tissue PAA were reflected by an increase in the PAA of euglobulin fractions concomitant with a decrease in antiplasmin activity in the blood samples obtained during the bleeding experiments.
The Application of a Monoclonal Antibody to Factor VIII Related Antigen (VIIIRAg) in Immunoradiometric Assays for Factor VIII
Authors: Thomas J E , Peake I R , Giddings J C , Welch A N , Bloom A L 
Published: July 2018

SummaryA two site solid phase immunoradiometric assay (IRMA) for VIIIRAg has been developed using a monoclonal antibody as both the solid phase ligand and the radiolabelled antibody. A range of normal plasmas and von Willebrand’s disease (vWd) plasmas has been assayed for VIIIRAg by this method and compared with VIIIRAg values measured by an IRMA using polyclonal antibodies and by immunoelectrophoresis and with ristocetin cofactor activity (VIIIRiCoF). It was found that the monoclonal IRMA correlated well with the polyclonal IRMA and the immunoelectrophoretic assay, but the correlation with the VIIIRiCoF assay was relatively poor, in spite of the strong inhibitory effect of the antibody on VIIIRiCoF activity.
Comparison of the Interactions of Fibrinogen and Soluble Fibrin with Washed Rabbit Platelets Stimulated with ADP
Authors: Harfenist Elizabeth J , Packham Marian A , Mustard J Fraser 
Published: July 2018

SummaryBecause fibrin, formed at a site of vessel wall injury, is involved in the formation and stabilization of a platelet aggregate or thrombus, we have studied reactions of fibrin with rabbit platelets. Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization, was used to prepare soluble fibrin. Fibrin alone did not cause aggregation of washed platelets, but addition of ADP caused aggregation and deaggregation identical to those observed in the presence of fibrinogen. Specific binding of 125I-fibrin to ADP- stimulated platelets was similar to that of 125I-fibrinogen, but 125I-fibrin did not dissociate, even in the presence of high concentrations of apyrase. High non-specific binding of 125I-fibrin was observed that was not associated with aggregation. EDTA, prostaglandin E1 (PGE1) and creatine phosphate/creatine phos- phokinase prevented ADP-induced aggregation in the presence of fibrin and caused rapid deaggregation when added after ADP. They also inhibited 125I-fibrin binding when added before ADP, and EDTA or PGE1 caused partial dissociation of bound 125I-fibrin. In vivo, fibrin may bind to stimulated platelets, polymerize, form a gel, and interact with components of the plasma, the platelet aggregate, and the exposed subendothelium.
Effects of Oral Contraceptives and Obesity on Protein C Antigen
Authors: Meade T W , Stirling Y , Wikes H , Mannucci P M 
Published: July 2018

SummaryIn 24 women using oral contraceptives, protein C antigen was higher than in 24 women of the same age and of the same degree of obesity who were not using OC. In the pooled data for all 48 women, there was an increase in protein C of about 1% (of standard) for each 1.0 mm increase in skinfold thickness. Protein C tends to be high rather than low in circumstances predisposing to thrombosis.
Fibrinogen Fragments X, Y, D and E Increase Levels of Plasma Fibrinogen and Liver mRNAs Coding for Fibrinogen Polypeptides in Rats
Authors: Princen H M G , Moshage H J , Emeis J J , de Haard H J W , Nieuwenhuizen W , Yap S H 
Published: July 2018

SummaryPreviously, we demonstrated that in vivo regulation of liver fibrinogen synthesis occurs via the fibrinogen mRNA level. However, the molecular regulatory mechanism of fibrinogen synthesis is still not well understood. Fibrinogen or fibrin degradation products might play an important role in regulating fibrinogen synthesis. In our present study, we have injected rats intraperitoneally with purified homologous fragments and measured the liver content of mRNA specific coding for fibrinogen. Increased levels of fibrinogen mRNA and elevated plasma fibrinogen concentrations were observed in rats after administration of fibrinogen degradation products X, Y, DEGTA Dcate or E. Fragment E or E’ has a less stimulatory effect than X, Y or Dcate, whereas cross-linked fibrin degradation product D dimer does not increase fibrinogen synthesis. This article reports for the first time a stimulatory effect of the high molecular weight fibrinogen degradation products on fibrinogen synthesis.
Methods in Dose Response Platelet Aggregometry
Authors: Thompson S G , Vickers M V 
Published: July 2018

SummaryA standardized method for performing dose response platelet aggregation has been developed, and has been used in about 1000 subjects in a large prospective study of ischaemic heart disease. A computer program has been used to fit a sigmoidal relationship between primary aggregation response rate and the log dose of aggregating reagent. Estimates of the parameters of the sigmoid curve are used to characterize an individual’s platelet aggregability. Methods for investigating the maintenance of long-term quality control have also been developed.
Human Platelet Aggregation and Release Reaction Induced by Platelet Activating Factor (PAF-Acether) – Effects of Acetylsalicylic Acid and External Ionized Calcium
Authors: Cattaneo Marco , Canciani Maria Teresa , Mannucci Pier Mannuccio 
Published: July 2018

SummaryThe effects of the cyclo-oxygenase inhibition on PAF-acether- induced human platelet aggregation and secretion are controversial. We studied the above parameters on citrated platelet-rich plasma of 12 normal subjects before and after the in vivo administration of acetylsalicylic acid (ASA). Individual sensitivities to PAF-acether were highly variable. ASA completely inhibited the platelet secretion induced by low concentrations of PAF-acether, but caused only partial inhibition when platelets were exposed to high concentrations of PAF-acether. The concentration of PAF-acether which overcame the cyclo-oxygenase inhibition varied substantially, depending on the individual sensitivity of the platelets to it. The addition of CaCl2 2 mM to the samples did not affect the extent of the platelet secretion, but increased irreversible aggregation in samples taken both before and after the ASA administration. These data suggest that low concentrations of PAF-acether stimulate the human platelet secretion by activating the cyclo-oxygenase pathway, whereas higher concentrations also trigger other mechanism(s) that suffice to induce human platelet secretion and full aggregation.
Cold Promoted Activation and Factor XII, Prekallikrein and C1-Inhibitor
Authors: Czendlik C , Lämmle B , Ducket F 
Published: July 2018

SummaryDuring incubation of plasma in the cold an amidolytic activity due to the kallikrein-α2-macroglobulin complex appears in the plasma of about 40% of the women under hormonal contraception. The factor XII and prekallikrein activity are significantly increased 151.9% and 112.4% respectively in the cold promoted activation positive plasmas (CPA pos) whereas the activity of C1-inhibitor is decreased, 76%. The quotient of the product of the C1-inhibitor and α2-macroglobulin values divided by the product of the FXII and prekallikrein values is significantly lower in the CPA pos plasma 0.49 than in CPA neg plasma 0.96 (p <0.05). These results alone do not explain the cold promoted activation, since a patient with a C1-inhibitor as low as 9% showed no increase of the amidolytic activity after a 24 hr incubation at 4° C. However, the addition of purified C1-inhibitor to a CPA pos. plasma inhibits the cold activation. Heparin at a concentration of 0.5 IU/ml delays the appearance of the amidolytic activity.
Influence of Cyproheptadine on Endotoxin-Induced Disseminated Intravascular Coagulation (DIC) in Weaned Pigs
Authors: Nowak G , Markwardt F 
Published: July 2018

SummaryChanges in the coagulation system typical of consumption reaction, microthrombosis in the lungs and other organs and haemodynamic disturbances caused by infusion of endotoxin in weaned pigs were prevented by treatment with the serotonin receptor antagonist cyproheptadine.
Nomenclature of Secreted Platelet Proteins – Report of the Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets
Authors: Kaplan Karen L , Niewiarowski Stefan 
Published: July 2018

SummaryStandard nomenclature for a number of secreted platelet proteins was agreed upon by The Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets. Platelet factor 4 will continue to be used for the molecule with high heparin affinity, subunit molecular weight of 7780, and the described amino acid sequence. β-Thromboglobulin will be used to designate β-Thromboglobulin (81 amino acids/subunit, β-mobility on cellulose-acetate electrophoresis, pI 7), low-affinity platelet factor 4 (85 amino acids/subunit, y-mobility on cellulose-acetate electrophoresis, pI 8), and platelet basic protein (94 amino acids/ subunit, pI 10) when these are measured immunologically in plasma, but that thromboglobulin with a superscript designation of the pI should be used when assays are conducted on samples after isoelectric focusing, and a subscript amino-terminal amino acid can be added when a purified protein is described. Thrombospondin will continue to be the designation for the high molecular weight trimer that has previously been called thrombospondin or glycoprotein G. Platelet derived growth factor will be used for the group of closely related proteins of molecular weight about 30,000 and isoelectric point about 10.
Influence of Low Molecular Weight Heparin on the Hemostatic System After Abdominal Surgery
Authors: Schmitz-Huebner U , Rüschemeyer C , Schulte H , Loo J van de 
Published: July 2018

SummaryThe hemostatic effect of two low molecular weight heparin fractions and of one unfractionated heparin preparation administered subcutaneously b. i. d. was examined in 6 healthy subjects and in 53 patients after major abdominal surgery. Among other tests platelet count, prothrombin time, fibrinogen, β-thrombo- globulin, antithrombin, antiplasmin, FPA and F-CB 3 related antigen, as well as various heparin activities, were repeatedly determined pre- and postoperatively. Under all tested conditions the low molecular weight fractions induced higher heparin levels, both in terms of anti-Xa and of anti-thrombin activity. No further significant differences of the laboratory results between the treatment groups were documented. Total blood loss measured at the first postoperative day was higher in patients with malignancy and negatively correlated with antithrombin and antiplasmin levels, while no relation was observed with the heparin activities and the other tested parameters. Whereas evidence for a hemorrhagic property of the tested low molecular weight heparin fractions was found, a particular mechanism underlying this effect could not be identified.
The Effect of the Synthetic Steroid ORG OD14 on Fibrinolysis and Blood Lipids in Postmenopausal Women
Authors: Walker Isobel D , Davidson J F , Richards A , Yates R , McEwan H P 
Published: July 2018

SummaryTwo groups of postmenopausal women were compared. One group of 13 was given the synthetic steroid Org OD14 to suppress climacteric symptoms and one group of 14 was given placebo. After a 2 week baseline period the subjects received daily for 12 weeks, either 2.5 mg Org OD14 or placebo. There were no significant differences between the groups pre-treatment. Compared with the placebo group, during treatment, the Org OD14 group showed the following significant differences: higher haemoglobin, haematocrit, platelet count, plasminogen, fibrinolytic activity on fibrin plates and antithrombin III and lower fibrinogen. No significant differences between the groups were found in α2 antiplasmin levels, total cholesterol, total triglycerides, bilirubin or transaminase levels but the Org OD14 group had significantly lower levels of HDL cholesterol. With the exception of the haemoglobin and haematocrit levels all of the differences had disappeared by 2 weeks post treatment.