bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular Distribution and Phosphorylation of Vinculin lsoforms in Human Blood Platelets
Authors: Bruin Taco , Asijee Guus M , Prins Arie , Wouter ten Cate Jan , Sturk Augueste 
Published: July 2018

SummaryIn this study we investigated human blood platelet vinculin microheterogeneity, the subcellular localization and phosphorylation of the different isoforrns before and after platelet stimulation. At least 5 vinculin isoforms could be detected, as well as metavinculin. These isofonns did not demonstrate a specific subcellular localization, i. e. their relative content was similar in cytoskeleton, membrane skeleton and cytosol. Upon platelet stimulation with thrombin a small increase in α’-vinculin was noted in all platelet subfractions. The cytoskeleton of non-stimulated platelets contained a minor quantity of vinculin. Upon thrombin stimulation of the platelets the cytoskeletal vinculin content increased significantly; previously we already reported a maximal n% incorporation of the total platelet vinculin content into the cytoskeleton upon stimulation. A phosphorylation of a minor vinculin-isoforrl, i. e. at the α’/α location was mainly detected in the cytoskeleton. This phosphorylation was observable in the non-stimulated platelet cytoskeletal vinculin. These findings argue against a regulatory role for vinculin phosphorylation in the uptake of the main isoforms of this protein in the platelet cytoskeleton upon thrombin stimulation. The function of the phosphorylated cytoskeletal vinculin remains to be established.
Heparin, DDAVP and the Bleeding Time
Authors: Schulman Sam , Johnsson Hans 
Published: July 2018

SummaryThe effect on the bleeding time of heparin, followed by an infusion with desmopressin (DDAVP) 0.3 Μg/kg or placebo in a randomized, double-blind set-up, was investigated in 20 patients treated for acute venous thromboembolism. The bleeding time was on the average prolonged by 90% (95% confidence interval 46% -134%) after at least 1 day of treatment with heparin. At that point DDAVP shortened the bleeding time by 23% with a confidence interval of −35% to −11% whereas the effect of placebo was −2% with a confidence interval of −23% to +20%. There was also a shortening of the APTT after DDAVP but not after placebo. It is concluded that DDAVP induces a partial reversal of the effect of heparin on the bleeding time, and that DDAVP should be tried in case of hemorrhagic problems.
Platelet Heparin-Neutralizing Factor (Platelet Factor 4)
Authors: Lüscher E. F , Käser-Glanzmann R 
Published: July 2018

SummaryThe heparin-neutralizing platelet factor (PF4) is released from platelets under the influence of inducers of aggregation and nucleotide-release in the form of a high-molecular weight complex. The heparin-neutralizing activity is carried by a basic protein of molecular weight 29,700, four of which combine with a proteoglycan carrier, which in turn consists of 4 chondroitin sulfate A residues and a peptide moiety.The carrier-PF4-complex dissociates at higher ionic strength into proteoglycan and PF4 proper ; both forms (bound and free) are active in the inactivation of heparin, which displaces PF4 from its natural mucopolysaccharide carrier.PF4 is localized in human platelets in storage organelles, most likely in the α-granules and not in the adenine nucleotide and serotonin containing dense bodies. It is released simultaneously with the contents of these latter organelles.The physiological significance of PF4 is mainly seen in the interference with the inhibition of the clotting system by heparin within and in the vicinity of platelet aggregates. Released in circulation in the course of intravascular platelet damage, it may contribute to a facilitation of thrombin formation and action, by removing heparin.Adequately purified PF4 does not interact with fibrinogen and its derivatives and therefore is not directly involved in the induction of intravascular coagulation or platelet aggregation.
A Case against Heparin Therapy of Intravascular Coagulation
Authors: Straub P. W 
Published: July 2018

SummaryAdministration of a potentially dangerous drug like heparin should not be based on theoretical considerations and innumerable case reports but 1) on a firm diagnosis and 2) on a critical evaluation of the clinical benefit.The validity of criteria for the diagnosis of intravascular coagulation (IC) is discussed. It is emphasized in particular that loss of fibrinogen into extravascular spaces can only be excluded by assays of the level and disappearance rate of serum proteins not subject to the proteolytic action of thrombin or plasmin.Even when the diagnosis can be reasonably established, heparin therapy in a particular condition should only be advocated if its clinical benefit has been demonstrated in controlled clinical trials.Our conviction that heparin has as yet a small if any place in the management of patients with so-called intravascular coagulations is based mainly on two sets of arguments, one stemming from a critique of the diagnosis of IC, the other from a general attitude in the evaluation of therapeutic procedures.
A Scanning Electron Microscopic Study of Platelets of Certain Animal Species
Authors: Jain N. C 
Published: July 2018

SummaryComparative morphology of platelets of the dog, cat, cow, horse, sheep, and goat was studied with the scanning electron microscope and was found generally similar. Most of the platelets were slightly biconvex or flat with relatively smooth surface and even contour. Some of these platelets had few short marginal filaments, or small shallow depressions or tiny protuberances on the surface. A small number of platelets exhibited surface irregularity and few long pseudopods which were thought to result from platelet activation during the processing of blood. The number of such irregular platelets increased in stored blood and in blood fixed at 4° C.
Protective Effect of Pantethine on Experimental Thrombocytopenia in the Rat
Authors: Ashida Shin-ichiro , Abiko Yasushi 
Published: July 2018

SummaryThe effects of pantethine on circulating platelet counts and platelet functions were studied in normal and experimentally produced thrombocytopenic rats.Administration of pantethine to normal animals did not cause any alterations in both platelet count and function except for a slight enhancement of intravascular platelet aggregation induced by collagen or neuraminidase.Injection of anti-rat platelet rabbit serum into rats resulted in acute thrombocytopenia. Administration of pantethine prior to the antiserum promoted recovery from the thrombocytopenia in a dose dependent manner, but administration of the drug after development of the thrombocytopenia was not effective. A similar result was obtained with a transient thrombocytopenia induced by exchange transfusion with platelet poor blood. Regardless of whether animals were treated with pantethine or not, the platelets newly generated during the course of recovery from thrombocytopenia were essentially normal in the function tested in vitro.A more chronic thrombocytopenia induced by repeated injections of the antiserum was prevented, to some significant degree, by daily administration of pantethine throughout the experimental period.In contrast to these, such effect of pantethine was not observed with the thrombocytopenia models produced by nitrogen mustard N-oxide and neuraminidase.These findings were discussed in relation to mechanism of the action of pantethine and to possible clinical application of the drug to thrombocytopenia.
Sodium Acetate Buffer
Authors: Chohan I. S , Vermylen J , Singh I , Balakrishkan K , Verstraete M 
Published: July 2018

SummarySodium acetate buffer, 0.12 M, pH 7.4 as a diluent in the low temperature technique of dilute clot lysis time, is more effective in accelerating the velocity of lysis than phosphate buffer of similar pH and molarity. A uniform shape of the clot is maintained throughout the digestion in sodium acetate buffer and the end point of lysis is characteristically marked by an abrupt and sharply defined disintegration. Sodium acetate buffer can be employed advantageously in this technique not only to improve the observation but also to shorten the lysis times.
The Inhibition of Urokinase by Aromatic Diamidines
Authors: Geratz J. D , Cheng Michael C.-F 
Published: July 2018

Summary1. Structure-activity relationships have been established for the inhibition of urokinase by aromatic diamidines. In an assay system employing purified urokinase and human plasminogen the most potent inhibitor was found in 4′,4″-diamidino-2-hydroxy-1,4-diphenoxybutane which proved 5600 times more active on a molar basis than epsilon-aminocaproic acid (E-ACA).2. 4′4″-diamidino-2-hydroxy-1,4-diphenoxybutane behaved as a competitive inhibitor of the urokinase catalyzed hydrolysis of Nα-acetyl-L-lysine methyl ester. At pH 7.85 and 37° C the Ki value was determined as 3.18 × 10–6 M which compares with a value of 6.79 × 10–5 M for p-aminobenzamidine and 3.57 × 10–2 M for E–ACA.3. In two fibrinolytic tests including urokinase as activator the superiority of diamidines over E–ACA was less marked than in the pure plasminogen activation system. This was due to the presence of certain plasma proteins in the fibrinolysis assays which augmented the inhibitory strength of E-ACA. The order of effectiveness of diamidines in the lysis tests was also different from the one in the activation test. In a human fibrin clot lysis test the most active inhibitor was 3′3″-diamidino-2-hydroxy-1,4-diphenoxybutane which was 1700 times more effective on a molar basis than E-ACA. In a human plasma clot lysis test the strongest inhibitor, 2-hydroxy-stilbamidine, was 70 times more powerful than E–ACA.
Molar Concentrations of Fibrinolytic Components, Especially Free Fibrinolysin, in Vivo
Authors: Nanninga L. B 
Published: July 2018

SummaryThe levels of fibrinogen and of Profibrinolysin (plasminogen) in urokinase-treated plasma as a function of time of incubation were measured. The Profibrinolysin concentration was estimated through its complete conversion to fibrinolysin and the inhibition of the enzyme by crystalline soybean trypsin inhibitor. The dissociation constant of the FL-STX complex was determined to be 7 × 10–9 M. The average concentration of Profibrinolysin in normal human citrated plasma was found to be 8 × 10–7 M. From the decrease of fibrinogen with time in the urokinase-treated plasma, the free fibrinolysin was calculated. Free fibrinolysin in normal human blood in vivo was estimated from the half-life of fibrinogen and other data obtained in this study to be present at a concentration of 1.7 × 10–10 M. The plasmakinase activity in vivo, expressed as urokinase molarity, is also about 2 × 10–10 M.
Essential Athrombia
Authors: Inceman Şeref , Tangün Yücel 
Published: July 2018

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”
Studies on the Platelet Defect in Alcoholism
Authors: Cowan Dale H , Graham Richard C 
Published: July 2018

SummaryPlatelet ultrastructure, protein composition, and adenine nucleotide metabolism were studied in patients ingesting ethanol to elucidate the mechanism of ethanol-induced changes in platelet function and survival. Serial measurements were made in 2 patients who maintained blood ethanol levels in excess of 300 mg/100 ml for 3 to 4 weeks. No major changes in structure or metabolism were detected in platelets from the patient whose platelet counts remained stable during the ingestion period. By contrast, the development of thrombocytopenia in the other patient was associated with significantly reduced intracellular ADP, increased ATP/ADP ratio, decreased release of ADP, increased specific radioactivity of intracellular ATP and ADP, and increased formation of hypoxanthine. Additionally, platelets from this patient varied markedly in size, contained giant granules, and possessed a poorly defined micro-tubular system. After stimulation with ADP or collagen, centripetal granule migration was retarded, and the aggregates formed were small and loose. Several large proteins were absent from the supernatant fraction of sonicated platelets from the thrombocytopenic patient. Exposure of normal platelets to ethanol in vitro resulted in no detectable change in platelet ultrastructure. The data indicate that the ethanol-related abnormalities of platelet function are due in part to subnormal amounts of intracellular ADP and a deficit in the storage pool of ADP. Additionally, the results suggest that impairment in the release mechanism to the observed defect in the release reaction.
The Significance of Malate Dehydrogenase Isoenzymes in Human Blood Platelets
Authors: Schneider W , Gross R 
Published: July 2018

SummaryTwo MDH isoenzymes were detected in the homogenate of normal human blood platelets. According to their properties the cationic isoenzyme is compartmentalized in the mitochondria, the anionic one belongs to the cytoplasma. In spite of the few mitochondria in human blood platelets the proportion of the cationic enzyme is relatively high.Both of these enzymes could belong to a transfer system for malate transport across the mitochondrial membrane. As human blood platelets do not contain creatine phosphate a system like that could be of significance for platelet function.
Platelet Adhesion, Release and Aggregation in Flowing Blood: Effects of Surface Properties and Platelet Function.
Authors: Baumgartner Hans R , Muggli Reto , Tschopp Thomas B , Turitto Vincent T 
Published: July 2018

SummaryPlatelet adhesion to natural and artificial surfaces and adhesion-induced aggregation were investigated in vitro using an annular perfusion chamber. The surfaces were exposed to anticoagulated blood under identical flow conditions (~ arterial shear rates). The initial attachment of platelets (contact) appeared less surface specific than spreading and release. Fibrillar collagen was the most powerful inducer of platelet degranulation whereas elastin, microfibrils and epon were virtually inactive. Fibrillar collagen caused release also in the absence of spreading. Surface coverage with platelets did not exceed 25 % unless spreading occurred. Perfusion with platelet-free plasma or platelet-poor blood did not remove adhering platelets. However, platelets were translocated from mural thrombi to the surface by such perfusion. In addition, platelets which detached from mural thrombi adhered more readily to elastin or microfibrils than platelets from the circulating blood. The initial attachment of platelets to subendothelium was inhibited in von Willebrand’s disease, the Bernard-Soulier syndrome and at high concentrations of dipyridamole; spreading was inhibited in storage pool disease of rats, at low temperature (20° C), with EDTA (3 mM) and Prostaglandin E1 (1 μM); and adhesion-induced aggregation was inhibited in thrombasthenia, storage pool disease and after ingestion of sulfinpyrazone or Aspirin.It is concluded that the initial attachment (contact) of platelets, spreading and surface-induced release of platelet constituents are at least partially independent phenomena, the latter two being highly surface specific. At flow conditions which cause the disappearance of platelet thrombi, platelet adhesion appears as an irreversible process.
Fibrinogen and its Derivatives: Cofactors in the Intrinsic Generation of Thrombin
Authors: Triantaphyllopoulos D.C , Ryan L.T 
Published: July 2018

SummaryThe simultaneous addition of suboptimal concentrations of factor VIII and intact or plas-min-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier of factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.
Studies on Chemically Modified Fibrinogen
Authors: Kloczewiak M , Wegrzynowicz Z , Matthias F.R , Heene D.L , Zajdel Maria 
Published: July 2018

SummaryTreatment of fibrinogen with maleic acid anhydride renders fibrinogen unclottable depending on the degree of modification of the molecule. According to radioactive studies the release of fibrinopeptides by thrombin or reptilase is undisturbed. The incoagulability is due to inhibition of the polymerization process of fibrinmonomers derived from modified fibrinogen, mainly caused by the increase of electronegative charges upon the fibrinogen molecule. According to discelectrophoretic analysis modified fibrinogen fails to produce fragments D and E following plasmic digestion, however, may be degraded to high molecular weight products. Modified fibrinogen reveals some similarities to abnormal fibrinogens in congenital dysfibrinogenemia with regard to its functional properties.
Enzymatic Removal of ADP from Plasma: Unaltered Platelet Adhesion but Reduced Aggregation on Subendothelium and Collagen Fibrils
Authors: Tschopp Th B. , Baumgartner H.R 
Published: July 2018

SummarySubendothelium of rabbit aorta and fibrillar collagen were exposed to citrated human or rabbit blood which was circulated through a perfusion chamber under flow conditions similar to those found in arteries. The resulting platelet adhesion and subsequent formation of platelet micro thrombi on the exposed surfaces were measured in 0.8 μm thick sections by a morphometry technique using light microscopy.Removal of plasma ADP by the substrate-enzyme combination CP-CPK (creatine phosphate-creatine phosphokinase; 3 mM and 90 U/ml blood) did not affect the initial attachment and spreading of platelets on subendothelium, whereas platelet thrombus formation was strongly inhibited. On free collagen fibrils CP-CPK was much less inhibitory on platelet thrombus formation but platelet adhesion again was not affected. It is concluded that platelet aggregation induced by thrombogenic surfaces in the presence of arterial blood flow is at least partially governed by ADP released from adhering platelets. Platelet adhesion to the examined surfaces, however, does not seem to be mediated by plasma ADP.
The Effects of Therapy with Oestriol Succinate and Ethinyl Oestradiol on the Haemostatic Mechanism in Post-Menopausal Women
Authors: Davies Terence , Fieldhouse Gillian , McNicol George P. 
Published: July 2018

SummaryThe effects on the haemostatic mechanism of oestrogen therapy, given to prevent bone loss in post-menopausal women, have been investigated. Oestriol succinate was given orally to 10 women at a level of 2 mg/day for 1 month and for a further 3 months with incremental increase of 2 mg each month. 6 of the 10 women were subsequently treated with 25 μg/day orally of ethinyl oestradiol. Oestriol succinate therapy resulted in a small increase in the level of factor VII, a decrease in factor VIII concentration and increased sensitivity of platelets to aggregating agents. Ethinyl oestradiol treatment resulted in much more widespread changes with marked increases in coagulation factors VII, VIII, IX and X, decreased levels of antithrombin and dramatic increases in circulating plasminogen levels and euglobulin lysis activity. The data suggested that the nature of oestrogens employed therapeutically is important in determining the qualitative and quantitative effect of oestrogen therapy on components of the haemostatic mechanism.
Blood Coagulation and Fibrinolysis in Thyroid Disease
Authors: Farid Nadir R. , Griffiths Brian L. , Collins John R. , Marshall William H. , Ingram David Wallace 
Published: July 2018

SummaryFibrinolytic activity and factor VIII concentration were studied in 30 patients with moderate to minimal hypothyroidism and in 7 patients with hyperthyroidism. In the hypothyroid group, the results were related to serum thyroxine levels, HL-A phenotypes and thyroid autoantibody titres. As serum thyroxine decreased so did factor VIII concentration, however, euglobulin lysis time was correspondingly prolonged. Factor VIII appears to be the most sensitive among coagulation factors to the deterioration of thyroid function tests. There was a significant correlation between the reciprocal of thyroid antibody titres and fibrinolysis; however, there was no relationship between factor VIII concentration or fibrinolysis and a specific HL-A phenotype although the incidence of HL-A8 was increased in the group as a whole.Euglobulin lysis time was prolonged in 6 out of 7 patients with Graves’ hyperthyroidism. Factor VIII was elevated in only 3 of these patients.
Comparative Sensitivity of Two Hemagglutination Inhibition Immunoassays for Fibrinolytic Degradation Products in Human Serum
Authors: Chi David S. , Chen James P. 
Published: July 2018

SummaryA new modification of hemagglutination inhibition immunoassay for measuring fibrino-gen/fibrin degradation products (FDP) using glutaraldehyde as a coupling reagent was introduced. This method was compared with the tanned-red-cell hemagglutination inhibition immunoassay (TRCHII). Sheep erythrocytes (SRBC) were sensitized with fragment D or E, respectively. The procedure of sensitizing SRBC is simple and can be achieved within 2 hrs. The sensitized SRBC stored at 4° C for 6 months did not lose their activities. The sensitivities for assaying D and E relative FDP were 0.32 μg/ml, respectively, which were slightly better than those of TRCHII. This represents the first adaptation of glutaraldehyde erythrocyte hemagglutination inhibition immunoassay (GEHII) for the estimation of FDP employing either microtiter plate or test tube. The microtechnique and test tube method were found to be essentially equivalent. The FDP level in the sera of normal individuals and patients suspected of elevation of FDP were assayed by both TRCHII and GEHII. By linear least squares analysis, the results show a significant correlation between these two methods. These results indicate GEHII is a simple, rapid and sensitive immunoassay for FDP in human serum.