bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble Crosslinked Fibrin(ogen) Polymers
Authors: Selmayr Eberhard , Müller-Berghaus Gert 
Published: July 2018

SummaryThe present study is concerned with the formation of fibrin-fibrinogen associations in the presence of FXIIIa while fibrinolysis was inhibited by aprotinin and EACA. SDS agarose-poly acryl-amide gel electrophoresis on 2.5% gels under non-reducing conditions and ultracentrifugation of the associations on urea-sucrose density gradients showed the formation of soluble crosslinked high molecular weight (HMW) fibrin-fibrinogen polymers with an estimated molecular size up to 10 times that of fibrinogen. After incubation of a mixture of 131I-fibrinogen (4 mg/ml) and 125I-desAA-fibrin (0.2 mg/ml) with FXIIIa (2 U/ml) for 1 h at 37ΰ C, about 5% of the fibrinogen and 80% of the fibrin was incorporated into the generated soluble HMW polymers. The detection of soluble crosslinked fibrin-fibrinogen polymers could be a useful diagnostic criterion for imminent DIC.
Uptake and Inactivation of Thrombin on Rabbit Aortic Endothelium Studied with Two Different Substrates
Authors: Swedenborg Jesper , Dryjski Maciej , Frebelius Siw , Olsson Per 
Published: July 2018

SummaryThe endothelium is an important compartment for uptake and inhibition of thrombin. The amount of enzymatically active bound thrombin can be detected with both small synthetic substrates and with aid of fibrinogen as substrate. The present study was designed to investigate the relation between endothelially bound thrombin with amidolytic activity towards a synthetic substrate (S-2238) and thrombin capable of converting fibrinogen by measuring generation of fibrinopeptide A (FPA). The luminal surfaces of rabbit aortae (2 cm2) were exposed in vitro to thrombin (0.625-5.0 NIH units/ml). Thrombin disappeared from the solution and a certain fraction was recovered on the surface. There was a linear relationship between the amount of thrombin on the surface and the concentration of thrombin in the incubation mixture. Approximately one third of the thrombin measured with S-2238 was also able to cleave fibrinogen. After incubation with defibrinogenated plasma almost total inhibition of fibrinogen splitting activity occurred within 30 sec. The inhibition of the amidolytic activity was less complete. When endothelially bound thrombin was exposed to plasma much less FPA was generated than in a fibrinogen solution. A minor fraction of endothelially bound thrombin was inhibited also upon incubation with Tyrode without recovery of any enzymatic activity in the solution. The results indicate that a fraction of thrombin bound to the endothelium has retained enzymatic activity and that a fraction of the enzymatically active thrombin is capable of converting fibrinogen. Inhibition of thrombin enzymatic activity occurs rapidly upon exposure to plasma. The endothelium itself has a minor inhibitory effect also in the absence of plasma. Thrombin with retained fibrinogen splitting activity may contribute to thrombotic events particularly if plasma inhibitors are insufficient. Thrombin with activity towards fibrinogen could be bound to GAG:s whereas thrombin active towards S-2238 could be bound to GAGrs TM or possibly other receptors.
The Effect of Heparin vs. Citrate on the Interaction of Platelets with Vascular Graft Materials
Authors: Kottke-Marchant Kandice , Anderson James M , Rabinovitch Albert , Huskey Richard A , Herzig Roger 
Published: July 2018

SummaryHeparin is known to affect platelet function in vitro, but little is known about the effect of heparin on the interaction of platelets with polymer surfaces in general, and vascular graft materials in particular. For this reason, the effect of heparin vs. citrate anticoagulation on the interaction of platelets with the vascular graft materials expanded polytetrafluoroethylene (ePTFE), Dacron Bionit (DB) and preclotted Dacron Bionit (DB/PC) was studied in a recirculating, in vitro perfusion system. Platelet activation, as shown by a decrease in platelet count, an increase in platelet release and a decrease in platelet aggregation, was observed for all vascular graft materials tested using heparin and was greater for Dacron and preclotted Dacron than for ePTFE. Significant differences between heparin and citrate anticoagulation were seen for platelet release, platelet aggregation and the relative ranking of material platelet-reactivity. However, the trends and time course of platelet activation were similar with both heparin and citrate for the materials tested.
Anticoagulant Properties of Extracellular Slime Substance Produced by Staphylococcus Epidermidis
Authors: Bykowska K , Ludwicka A , wegrzynowicz Z , Lopaciuk S , Kopeć M 
Published: July 2018

SummarySlime produced by S. epidermidis strain KH 11 was extracted with phenol-saline. The saline phase was fractionated on a DEAE-Sepharose CL-6B column. The crude slime solution and its phenol-saline fraction were found to possess anticoagulant properties. They inhibited the coagulation of human plasma by thrombin, prolonged the activated partial thromboplastin time, but did not change the rate of plasma coagulation by reptilase. The anticoagulant effect of slime could be neutralized by rather high concentrations of protamine sulphate. In the presence of plasma, the staphylococcal slime also inhibited in a concentration dependent fashion the amidolytic activity of thrombin and factor Xa against synthetic chromogenic substrates. Both antithrombin III (AT III) and other plasma component(s), presumably heparin cofactor II, were required for the full expression of the slime effect. The anticoagulant action of slime was markedly less AT III dependent than that of heparin. The activity was resistant to heating (100° C, 30 min). Slime and its fractions were stronger inhibitors of thrombin than of factor Xa. Fraction IV separated by DEAE-Sepharose chromatography and particularly rich in galactose and glucuronic acid had the highest inhibitory potency. It is conceivable that slime component(s) similar to glycosaminogly-cans from other sources can carry the anticoagulant activity.
The Use of a Functional and Immunologic Assay for Plasma Protein C in the Study of the Heterogeneity of Congenital Protein C Deficiency
Authors: Bertina R M , Broekmans A W , Es C Krommenhoek-van , Wijngaarden A van 
Published: July 2018

SummaryProtein C is a vitamin K dependent protein involved in blood coagulation. A congenital deficiency in protein C antigen - which inherits as an autosomal dominant disorder - has been reported to be associated with a high risk for thrombo-embolic disease at relatively young age. In the present paper we report on the development of a functional assay for plasma protein C. In this assay protein C is adsorbed to Al(OH)3, eluted and activated by thrombin, after which the concentration of the activated protein C is measured with a peptide substrate (S2366). Normal values for protein C activity and protein C antigen were determined in healthy volunteers and patients on stable oral anticoagulant treatment. Protein C activity and antigen levels were compared in 28 patients from 9 different pedigrees with both congenital protein C deficiency and thrombotic disease. Two types of protein C deficiency could be recognized: in type I the deficiency is due to the absence or reduced presence of protein C molecules, while in type II the deficiency is caused by the presence of an abnormal protein C molecule with strongly reduced functional activity.
Preparation and Characterization of NH2-Terminal Fibrinogen Bβ Fragments from N-DSK of Human Fibrinogen
Authors: Birken S , Agosto G , Lahiri B , Canfield R 
Published: July 2018

SummaryIn order to investigate the early release of NH2-terminal plasmic fragments from the Bβ chain of fibrinogen, substantial quantities of Bβ 1-42 and Bβ 1-21 are required as immunogens, as radioimmunoassay standards and for infusion into human volunteers to determine the half-lives of these peptides. Towards this end methods that employ selective proteolytic cleavage of these fragments from fibrinogen have been developed. Both the N-DSK fragment, produced by CNBr cleavage of fibrinogen, and Bβ 1-118 were employed as substrates for plasmin with the finding of higher yields from N-DSK. Bβ 1-42 and Bβ 1-21 were purified by gel filtration and ion-exchange chromatography on SP-Sephadex using volatile buffers. When the purified preparation of Bβ 1-42 was chromatographed on reverse-phase high performance liquid chromatography, two peaks of identical amino acid composition were separated, presumably due either to pyroglutamate or to amide differences.
Influence of Noise on Blood Coagulation
Authors: Chohan I S , Singh I , Rai R M 
Published: July 2018

SummaryA study conducted in rats exposed to a continuous noise of 110 decibels over a period of 3 weeks revealed development of significantly prolonged bleeding time, higher plasma fibrinogen content, and progressively shorter activated partial thromboplastin time in test animals. These changes suggest a coagulopathy induced by noise stress.
The Effect of Albumin Bound Polyunsaturated Fatty Acids on Human Platelets
Authors: Holme Stein , Brox Jan H , Krane Hedvig , Nordøy Arne 
Published: July 2018

SummaryPlatelet rich plasma (PRP) was incubated at 22–24° C for 24 hr with various polyunsaturated fatty acids (PUFA), bound to albumin, to determine whether changes in the FA composition of the platelet phospholipids might induce changes in platelet behavior and in platelet structural integrity. The PUFA tested were linoleic (18:2 w6)*, linolenic (18:3 w3), dihomo-gamma linolenic (20:3 w6), arachidonic (20:4 w6) and eicosapentaenoic acids (20:5 w3). Only PRP incubated with 20:3 w6 and 20:5 w3 incorporated significant amounts of these FA into the platelet phospholipids and showed inhibition of aggregation and TxB2 production with collagen. However, the inhibition was not due to the incorporation of these FA’s into the phospholipids as observed by washing and resuspension of the FA incorporated platelets in control plasma, or to any change in structural integrity. It is suggested that the effect of 20:3 w6 and 20:5 w3 on aggregation is due to metabolites of these FA’s released from the platelets.
The Effect of Collagen Mediated Platelet Release on Plasma Prekallikrein Activation
Authors: Weerasinghe K M , Scully M F , Kakkar V V 
Published: July 2018

SummaryCollagen mediated platelet aggregation caused -5.6 ± 6.7% inhibition and +39.1 ± 15.2% potentiation of prekallikrein activation in plasma from normal healthy volunteers between 20–40 and 50–65 years of age, respectively (n = 15, p <0.01). The amouns of platelet factor-four (PF4) released in the two groups were not significantly different. Collagen treatment in the presence of indomethacin caused +11.5 ± 3.6% and +59.6 ± 19.5% potentiation in the 20–40 and 50–65 age groups respectively (p <0.02). Adrenaline mediated platelet aggregation caused -55.2 ± 7.1% and -35.2 ± 8.3% inhibition in the 20–40 and 50–65 age groups, respectively. Collagen treatment of platelet-deficient-plasma and platelet-rich-plasma in EDTA also caused potentiation of prekallikrein activation.The results indicate that the observed degree of prekallikrein activation after platelet aggregation is a net result of the inhibitory effect of PF4 and the potentiatory effect of activated platelets. The potentiatory effect was greater after collagen treatment as compared to adrenaline treatment, and in the 50–65 age group as compared to the 20–40 age group.
The Inability of Propranolol and Aspirin to Inhibit the Response of Fibrinolytic Activity and Factor VIII-Antigen to Infusion of DDAVP
Authors: Brommer E J P , Derkx F H M , Barrett-Bergshoeff M M , Schalekamp M A D H 
Published: July 2018

SummaryWe tested the response of the fibrinolytic activity and factor VIII-antigen levels to infusion of DDAVP in healthy volunteers and we studied the influence of propranolol and aspirin on this response. After DDAVP, 0.4 μg/kg in 10 min i. v., the fibrinolytic activity of redissolved euglobulins rose from 179 to 452 mm2 (lysis area of fibrin plates); after pretreatment with propranolol, 320 mg per day during 7 days, DDAVP induced a similar rise (from 166 to 471 mm2) and after pretreatment with a single dose of aspirin, 600 mg, ingested 5 hr before the DDAVP infusion, the lysis area increased from 159 to 455 mm2
Factor VIII-antigen level increased within 60 min after DDAVP from 104 to 208%; after pretreatment with propranolol from 111 to 230% and after a single dose of aspirin, DDAVP induced a rise from 107 to 206%.From these data we conclude that neither baseline levels nor the release of plasminogen activator or factor VIII after DDAVP infusion are influenced by β-blockade or by interference with prostaglandin synthesis.
Drugs Effect on Platelet Survival Time: Comparison of Two Pyrimido-Pyrimidine Derivatives in Patients with Aortic or Mitral Replacement
Authors: Schbath J , Boissel J P , Mathy B , Ville D , Benveniste E , Sanchini B , Leizorovicz A , Belleville J , Dechavanne M , Maitre P , Gillet J , Bentamar A 
Published: July 2018

SummaryA prospective randomized trial of the effects of 2 antiplatelet aggregating drugs, dipyridamole (375 mg/d), a related substance RA 233 (1500 mg/d) and placebo, concomitantly with oral anticoagulants, was carried out in patients with prior valvular replacement. The study was aimed to determine effect on platelet survival time (PST) of these 2 agents. The trial sample consisted of 40 males and 15 females aged 40–70 years (average 53 years). 32 received Björk-Shiley valve in aortic position; 23 underwent mitral valve replacement: 3 with Cooley-Cutter, 11 with Lillehei- Kaster 500 and 9 with Starr-Edwards 6120 prostheses; 28 patients had aortic stenosis, 21 aortic insufficiency. All the PST measured after 3 months of treatment were within normal ranges and not different between placebo, dipyridamole or RA 233 treated subjects: averages in days were, respectively, 7.49, 7.11 and 6.88. The present study did not support the claim that modem valve prosthesis could lead to a shortened PST.
An Antiplatelet Monoclonal Antibody That Inhibits ADP and Epinephrine-Induced Aggregation
Authors: Vilella R , Lozano T , Mila J , Borche L , Ercilla G , Ordinas T , Vives J 
Published: July 2018

SummaryA monoclonal antibody (Mab) named EDU-3, was produced by fusing splenocytes from one Balb/c mouse, immunized with a mixture of platelets and non-T cells from heparinized human peripheral blood, with the HAT-sensitive myeloma line P3-NS1/ l.Ag4.1. By indirect immunofluorescence (IF) it was seen that this Mab reacted with all normal human platelets and bone marrow megakaryocytes, but did not react with lymphoid cells from normal donors, or platelets from Glanzmann’s thrombasthenia (GT) patients. Immunoprecipitation and SDS-PAGE experiments demonstrated that this Mab recognizes an epitope on the IIb-IIIa glycoprotein complex (GPC). EDU-3 inhibited platelet aggregation and release of ATP induced by ADP and epinephrine. Aggregation induced by arachidonic acid, ristocetin and bovine factor VIII were not inhibited by EDU-3. The difference between EDU-3 and other Mab directed against the IIb-IIIa GPC is discussed.
Response of Femoral Venous Oxygen Tension to Graduated Pressure Stockings - Possible Relationship to Deep Vein Thrombosis
Authors: Okoye G C , Evans J H , Beattie J , Lowe G D O , Lorimer A R , Forbes C D 
Published: July 2018

SummaryVenous oxygen tension (pO2) was measured in discrete samples of blood obtained through the femoral vein of cardiac catheterisation patients before, during and after application of sustained external graduated pressure in the form of compression stockings (T. E. D. Kendall). There was a significant reduction (p <0.05) of pO2 from the baseline value both 30 sec and one minute after the application of the pressure stockings. Thereafter, the pO2 rose to baseline values. Two minutes after the stockings were removed there was again a significant reduction (p <0.05) of pO2 from the baseline value. We suggest that the decrease in ivenous pO2 on application of external pressure may be a reflection of washing out of stagnant hypoxic blood from the venous valve pockets, which may be related to the formation of deep vein thrombosis (DVT).
A Quick Method for Screening Platelet Dysfunctions Using the Whole Blood Lumi-Aggregometer
Authors: Ingerman-Wojenski Carol M , Silver Melvin J 
Published: July 2018

SummaryPatients who present with a clinical history suggesting a bleeding disorder are often tested initially for a clotting defect rather than for platelet dysfunction, due to the length of time necessary to complete a platelet function study in platelet-rich plasma. We have developed a sensitive method for measuring platelet aggregation and release of ATP employing the Whole Blood Lumi-Aggregometer. This method makes it possible to quickly detect patients who require further study for possible platelet function disorders such as cyclooxygenase deficiency, storage-pool defect, thrombasthenia, and von Willebrand’s disease. The results obtained with this electrical impedance instrument do not differ from those obtained with the conventional optical method. However, it is now possible to recognize a platelet function defect within 30 min of obtaining a 5 ml sample of citrated whole blood. Further, platelets of unusual size or density are not lost to testing through centrifugation.
A Cooperative Clinical Trial of High-Dose Immunoglobulin Therapy in 177 Cases of Idiopathic Thrombocytopenic Purpura
Authors: Uchino Haruto , Yasunaga Kojiro , Akatsuka Jun-lchi 
Published: July 2018

SummaryA study was conducted with the cooperation of 31 university hospitals and 44 general hospitals in Japan on high-dose immunoglobulin therapy for idiopathic thrombocytopenic purpura (ITP).Sulfonated immunoglobulins were administered to 177 patients, comprising 102 children and 75 adults for two to seven days, and a favorable rise of platelet count was found in 114 (64.4%) of these patients.In particular, of the 107 patients who had not responded favorably to adrenocortico-steroids therapy, 63 cases showed a favorable rise of platelet count. And of the 14 patients who had not responded favorably to splenectomy, 6 cases showed a favorable rise of platelet count.In the majority of cases the platelet count fell to its pretreatment level within one month after the start of sequence of administration.Although a dosage of 400 mg/kg/day was suitable for most patients, the wide range of individual responses suggested the desirability of determining an optimal dose for each patients.
Observations on the Heparin Neutralizing Activity of Outdated Platelet Concentrates
Authors: Griffiths B L , Collins J R , Huntsman R G 
Published: July 2018

SummaryA crude extract of outdated, washed, frozen and thawed, platelet concentrates was prepared and optimally diluted for use in the A. P. T. T. test as a source of platelet phospholipid (P. F. 3). The extract contained, in addition to P.F. 3, active heparin neutralizing activity (P. F. 4), which was able to neutralize plasma heparin up to a concentration of approximately 0.8 units/ml plasma. Although these observations are of a preliminary nature, it is felt that the extract can be used to follow the “intrinsic” coagulability of plasma samples from patients receiving therapeutic heparin. Utilizing the A. P. T. T. test system, the determination of coagulability and the neturalization of heparin result from the use of this extract in a single test.
Further Characterization of Human Platelet Activation in the Absence of Aggregation: Phosphorylations of Specific Proteins and Relationship with Platelet Secretion
Authors: Nunez Danièle , Levy-Toledano Sylviane 
Published: July 2018

SummaryPlatelet aggregation and secretion have been described to be associated with phosphorylation reactions. Thrombasthénie and EDTA-treated control platelets undergo a normal serotonin release in the absence of aggregation. We now studied the phosphorylation of specific proteins associated with platelet secretion. In the presence of ionophore, significant increases occurred in the phosphorylation of two polypeptides of 43,000 and 20,000 molecular weight (P43 and P20) in a concentration dependent manner, and this was accompanied by an increase in the 14C-5HT release. The 32P-labelling of P43 and P20 reaches a peak within 1 min of platelet activation and is followed by a rapid dephosphorylation over the next 2-10 min. While the P20 is identified as the myosin light chain, the identity and the function of the P43 remain unknown.Isoelectric focusing separates 4 proteins from P43 during two dimensional electrophoresis, but only one of them is phosphorylated by A 23187. Chlorpromazine (CPZ) and trifluoperazine (TFP) inhibit the P43 and P20 phosphorylation as well as the 14C- 5HT release in a dose dependent manner. The inhibitory action of the drugs is more pronounced for P43 than for P20, especially when the reactions are carried out at 20° C instead of at 37° C, while the release reaction is still inhibited under these conditions. These results allow different hypotheses for the relationship of phosphorylation-secretion and indicate the importance of one of these proteins (P43) for the release reaction.
Immunological Alterations in Haemophiliacs Treated with Lyophilized Factor VIII Cryoprecipitate from Volunteer Donors
Authors: Ceuppens J L , Vermylen J D , Colaert J , Desmyter J , Gautama K , Stevens E , The A L , Vanham G , Vermylen C , Verstraete M 
Published: July 2018

SummaryWe studied immune function in Belgian haemophiliacs treated with Factor VIII from volunteer donors. No patient had clinical evidence of immune deficiency. We found a decrease in T-helper cells (p <0.0005), in the ratio of T-helper over T-cytotoxic/ suppressor cells (1.72 ± 0.47 versus 2.24 ± 0.82 in controls, p <0.005) and in lymphocyte responsiveness to mitogens (p <0.05).These findings could not be linked to the amount of F VIII received over the last year, the time since last F VIII administration, circulating immune complexes (54% positive patients, 7% positive controls, p <0.005), increased ALT levels, antibodies to cytomegalo-virus (85% of the patients, 45% of the controls, p <0.005), antibodies to Epstein-Barr virus, nor to the presence of HLA-DR 5 which was found in 56% of the haemophiliacs (20% of the overall Belgian population, p <0.005).Either F VIII induces long lasting immunological alterations unrelated to AIDS, or haemophilia is itself associated with such changes.
The Anticoagulant Effects of the Hookworm, Ancylostoma ceylanicum: Observations on Human and Dog Blood In Vitro and Infected Dogs In Vivo
Authors: Carroll S M , Howse D J , Grove D I 
Published: July 2018

SummaryExtracts of adult Ancylostoma ceylanicum prolonged the prothrombin time (PT) and partial thromboplastin time with kaolin (PPTK) of both human and dog plasmas in vitro. Excret-ory/secretory (E/S) products of these worms had similar effects while larval extract prolonged the PTTK only. Thus, the anticoagulant activities of this parasite are dependent upon the stage of the worm’s life cycle. Collagen- and ADP-induced platelet aggregation were inhibited by adult and larval extracts. When the peripheral blood and bleeding times of dogs with varying worm burdens were examined, the only abnormality was shortening of the PTTK in the most heavily infected animals. Homogenates of dog small bowel subjacent to adult hookworms prolonged the PT of dog plasma and electron microscopical examination of this tissue revealed aggregation of platelets in blood venules without fibrin deposition. Thus, this study provides evidence that the anticoagulant properties of hookworms may have biological significance in infected animals.