bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Antithrombotic Properties of Suloctidil in Patients with Substitute Heart Valves
Authors: Moriau M. , Ferrant A. , Beys C. Col-De , Hurlet A. , Chalant C. , Ponlot R. , Jaumain P. , Goenen M. , Masure R. 
Published: May 2019

Isotopic platelet survival time (PST), platelet count, adhesiveness, aggregation, PF4 release and coagulation parameters were examined in 23 patients with prosthetic heart valves (6 mitral, 10 aortic and 7 mitroaortic Starr Edwards or Bjork valves) treated with or without suloctidil.The patients were distributed in 2 comparative groups : the treated group with 11 patients with VKA (nicoumalone) and suloctidil (600 mg/day) and the control group with 12 patients with VKA alone. The biological parameters were performed before (the 10th postop. day) and 6 weeks after treatment with or without suloctidil.Before treatment were : PST shortened, platelet adhesiveness and aggregation normal and PF4 release, factors I, VIII-C, VIII-R-Ag increased in both groups.After treatment, PST returned to normal in the treated group, but remained unchanged or was more decreased in the control group. Platelet adhesiveness and aggregation were unchanged in both groups. PF4 release was reduced in the treated group and unchanged in the control group. Platelet count, factors I, VIII-C, VIII-R-Ag returned to the preoperative values in both groups.Two severe thromboembolic complications appeared in the control group, none in the treated group.
A Study of Polymerization Sites in Bovine Fibrinogen
Authors: Tranqui L. , Chapel A. , Suscillon M. 
Published: May 2019

Abnormalities in bovine fibrinogen polymerization have been brought about by slight proteolysis on the native molecule by two purified aminopeptidases that we have called A and B and which come from bacteria. These degraded molecules have a molecular of between 272000 and 250000. The aminopeptidase A induces the Polymerization of fibrinogen into ordered structures, the period being 8 nm, when the ionic strength (I) is between 0.1 and 0.2. Fibrinogen modified by the aminopeptidase B precipitates at 4°C (0.075 < I < 0.2)into fibre with a major period of 45 nm. The action of thrombin on these modified fibrinogen molecules at I = 0.3 gives fibres each with two minor striations, whose distribution was however different. These structures were totally different from those of fibrin fibres with its typical major period of 23 nm and its three minor striations. The analysis of the polypeptide chains, the N-terminal-acids and the amino-acids composition of these degraded fibrinogen molecules enables us to differentiate the respective rolesof the polymerization sites in the N and C terminal parts of the Act and Bβ chains.Therefore, according to our hypothesis the fibre structures obtained from fibrinogen depend on the type of the sites which are discovered on fibrinogen by enzymatic splits and by slight conformational changes.
Purification and Partial Characterization of Rat Fibrinogen (rat-Fbg)
Authors: Nieuwenhuizen W. , van Ruijven-Vermeer Irina A.M. 
Published: May 2019

Rat-Fbg was purified from rat plasma using Sepharose-1ysi ne chromatography, repeated ammonium sulphate precipitation (35% saturation) and gel chromatography on Sepharose 6B.In order to minimize proteolytic activity, rats were injected intravenously with Trasylol before bleeding, and the collected blood was treated with Trasylol and DFP.A preparation was obtained, which was 95% clottable and showed a single band on SDS-poly-acrylamide gel electrophoresis. Alanine was the only detectable am i no-term i na 1 amino acid.After reduction and modification of the SH groups the material could be separated into three distinct chains (Aα, Bβ and γ) by pore-limit Polyacrylamide slab-gel electrophoresis in sod i urn dodecyl sulphate. The amino acid composition of the whole Fbg and of the separated modified chains were determined. The molecular weights were 61,000, 58,000 and 51,000 for Aα, Bβ and γ-chains, respectively.In as far as the chains are concerned, our results are in contrast with the findings of Bouma et al. (J. Biol. Chem. 250(1975) 4678), who could not discriminate between Aα- and Bβ-chains in SDS-polyacry1 am i de gel electrophoresis. Evidence will be presented that this can be due to Aa-chain degradation caused by incomplete inhibition of proteolytic enzymes during the purification.It is concluded, that complete inhibition of proteolytic activities in all purification steps is essential to obtain native fibrinogen. Moreover, in contrast to the conclusions of Bouma rat-Fbg does not differ essentially from Fbg from other mammalian species.
Ultrastructural Study on in Vivo Blood Compatibility of Biolized Materials
Authors: Harasaki H. , Picha G. , Helmus M. , Fields A. , Kiraly R. , Nose Y. 
Published: May 2019

The long-term implantation of cardiac prostheses has been hampered by the lack of thromboresistant blood interfacing materials. Glutaraldehyde treated pericardium and glutaraldehyde treated, gelatin-coated rubber have been utilized for the blood contacting materials of our devices. These “biolized” cardiac prostheses were implanted in calves: 8 total artificial hearts for up to 5 months, 7 left ventricular assist devices for up to 7 months, and a passive pump implanted in the aorta for 5 1/2 years. The blood-solid interaction and endothelialization of these materials were chronologically followed at an ultrastructural level using scanning and transmission electron microscopy.The devices implanted up to 40 days were covered by a thin layer of fibrinous material. The adhesion of blood corpuscles were minimal except for the region of diaphragm-housing junction. The majority of the adhered platelets were “contact” and “spread” platelets. Once this fibrin-rich layer was formed, no significant thrombus formation was observed. The endothelialization was observed in the portion of the pericardium surface adjacent to the inflow valve in the heart implanted for 145 days. The coverage of the endothelial cells was more complete in the passive pump. Although Weibel-Palade bodies were observed in the cytoplasm of these cells, they were characterized by the sparse microvillous projections, small number of pinocytotic vesicles, and widely opened intercellular junctions. In the subendothelial layer, no basement membrane was observed.The study showed the aldehyde treated collagen and gelatin are suitable materials as blood contact surfaces of the cardiovascular devices.
Radioimmunoassay of Human Platelet Factor 4
Authors: Chesterman C.N. , McGready J.R. , Morgan F.J. 
Published: May 2019

Plasma levels of the platelet specific protein, platelet factor 4 (PF4), may reflect alteration in platelet turnover or activation. Measurements more sensitive and specific than bioassay are required to test this hypothesis.Highly purified human PF4 prepared by affinity chromatography on heparin/agarose and cation exchange chromatography has been used to develop a sensitive radioimmunoassay. A standard double antibody technique with goat antirabbit serum as second antibody has been used. Anti-PF4 antibody was raised in rabbits with the multiple subcutaneous injection technique. Following a single booster an antibody was obtained which, at a final dilution of 1:75,000, binds 37% of tracer PF4. Iodinated tracer PF4 was produced by the lactoperoxidase labelling technique and purified by gel chromatography in heparin containing buffer to prevent absorptive losses. The assay buffer also contains heparin 1 U/ml.The tracer shows good stability (4-8 weeks) and adequate immunoreactivity. Non-specific binding was 2.4 ± 0.8% in 11 consecutive assays. Sensitivity of the assay, expressed as 50% displacement of the tracer, is normally 0.3-0.4 ng per tube with a working range of 0.06-1.25 ng (20-80% displacement). Twelve replicate determinations of a single plasma sample yielded a within-assay standard deviation of 0.6 ng/ml and coefficient of variation of 0.1%. The assay is highly specific, the closest cross reactivity being obtained with β-thromboglobulin which produces 50% displacement of tracer with 5 μg/tube. Plasma preparation may not yet be optimal, but normal values in carefully prepared samples lie below 10 ng/ml.
Detection, Purification and Comparison of Factor IX-Like Molecules
Authors: Bertina R.M. , Veltkamp J.J. 
Published: May 2019

An antibody specifically precipitating human factor IX has been raised in rabbits using highly purified factor IX (batchwise DEAE-Sephadex adsorption and elution, chromatography on heparin-Sepharose, disc-polyacrylamid gel electrophoresis; MW(SDS), 67,000).With an electro-immuno-assay for factor IX 6 hemophilia B+ families were detected (only one of which showed a prolonged prothrombin time with ox-brain thromboplastin). All factor IX like material demonstrated normal electrophoretic mobility (when mixed with normal plasma) under standard conditions.From one patient (hemophilia BM) the factor IX-like material has been purified at least 3000 times and compared with normal factor IX. The factor IX-like material from all B+ families has been compared with normal factor IX with respect to their behaviour in 2-dimensional electrophoresis at different time intervals after the initiation of contact-induced coagulation. The precipitation peak of normal factor IX gradually disappears after activation. Improvement of the precipitation conditions during electrophoresis by the addition of poly ethylene glycol at least partially prevents this phenomenon.Finally, it is concluded that the use of a precipitating antibody against factor IX is a valuable tool in the study of factor IX-like molecules.
Activation of Human Factor X
Authors: Orthner Carolyn L. , Morris Sam , Kosow David P. 
Published: May 2019

Factor X is the zymogen of the proteolytic coagulation enzyme Factor Xa. Since the activation of Factor X to Factor Xa may be a rate limiting step of the coagulation cascade we have begun investigations of the mechanism of this reaction. Human Factor X has been purified 6000-fold from human plasma and the final product is over 95% pure as judged by Polyacrylamide gel electrophoresis. Human Factor X has a monomeric molecular weight of 75,000 and consists of two chains held together by a disulphide bridge. The molecular weight of the heavy chain is 56,000 and that of the light chain is 17,500. The venom coagulant protein of V. russelli (RVV-X) activates human Factor X by cleaving the heavy chain. When fully activated, human Factor Xa shows two bands on Polyacrylamide gel electrophoresis indicating that human Factor Xa like the bovine enzyme has two molecular forms.The kinetic mechanism of the activation reaction has been investigated utilizing the chromogenic Factor Xa substrate Bz-Ile-Glu-Gly-Arg-p-Nitroanilide (S-2222). The reaction has an absolute requirement for Ca; Mg cannot substitute for Ca, however Mg can increase the Vmax of Xa formation in the presence of suboptimal concentrations of Ca. Both Ca and Mg effects exhibit positive cooperativity. Our data indicate that human Factor X has at least three cooperative metal binding sites some of which are specific for Ca.
The Effect of Fibrinogen Degradation Products on in Vitro Lymphocyte Function
Authors: Harvey H.A. , Albright C. , Lipton A. 
Published: May 2019

Fibrinogen Degradation Products (FDP) are increased in the sera of patients with advanced cancer and other immunosuppressive states. We studied the effect of micromolecular FDP on the function of normal human lymphocytes.FDP were obtained by prolonged digestion of human fibrinogen with plasmin. Plasmin was prepared from plasminogen by activation with Streptokinase in 0.1M tris buffer, pH 8.0 at 37°C. After dialysis and lyophilization, terminal FDP were reconstituted in phosphate buffered saline, sterilized and added in varying concentration to a lymphocyte microculture system, sRBC and EAC rosette assays and a Lexy plate Migration Inhibition Factor assay (MIF).FDP exhibited dose dependent inhibition of lymphocyte blastogenesis induced by the mitogens Phytohemagglutinin (PHA), Concanavillin A (Con A) and Pokeweed (PWM). FDP incubated with lymphocytes had no effect on MIF production or on T and B lymphocyte Rosette formation. FDP were further separated by gel electrophoresis on G–25 Sephadex column. Three peaks were obtained. Peaks 1 and 2 inhibited mitogenic response and Peak 3 enhanced PHA induced lymphocyte blastogenesis. Peaks obtained from the column were further characterized by isoelectric focusing.Micromolecular FDP appear to play a role in the non-specific modulation of lymphocyte functions that depend on cell replication. Their role should be further investigated in clinical immunosuppressive states.
A Study on Coagulation Factors, Platelets and Inflammation in Burns
Authors: Boisseau M.R. , Hourdillé P. , Bernard P. , Pradet A. , Soria J. , Soria C. 
Published: May 2019

A kinetic study on Burns was performed regarding both coagulation and platelet nucleotides on one hand and Prekallicreine levels on the other hand. These measurements were made as early as possible at the onset and over a long period of time. 1) At the initial phase, a Disseminated Intravascular Coagulation was detected (D.I.C.) hardly noticeable in the biological field. Fibrinogen and Fibrin degradation products were close to normal. The only way to make a diagnosis was by practising very sensitive research tests for soluble monomer complexes. 2) Platelet abnormalities were found : To begin with, a thrombopenia with a breaking down of the nucleotides showing an Acquired Storage Disease (A.S.D.), thena progressive rise until normal values for the nucleotides and higher values for platelet levels were reached, this last point connected with the inflammatory process. 3) Variations in Prekallicreine levels were observed in strict parallel directions with those of the platelet nucleotides.The relationship between D.I.C., A.S.D. and inflammation was thus brought to light.
Platelet Glycocalicin
Authors: Jamieson G.A. , Okumura T. 
Published: May 2019

Glycocalicin is a high molecular weight glycoprotein (Mr 150,000) present on the outer surface of platelets and obtained in soluble form following platelet homogenization. Glycocalicin has been purified and shown to bind to thrombin and to Factor VIII and to inhibit platelet aggregation caused-by these reagents. When solubilized from membranes, the thrombin-binding ability of glycoprotein I is identical with that of glycocalicin and the amount of thrombin bound is proportional to the amount of glycocalicin/glycoprotein I present on platelets. The thrombin-binding site has been located in the (nonglyco)peptide “tail” portion (Mr 40,000) of glycocalicin. These results suggest that glycocalicin plays a central role in platelet function.This work was supported, in part, by PHS Grants HL 14697 and AI 09017.
Changes in Euglobulin Lysis Following Intermittent Pneumatic Calf Compression
Authors: Stevenson Mabel M. , Rohr Paul R. , Davidson Ann G. , Byars Edward F. , Hopkins Gordon , Tarnay Thomas J. 
Published: May 2019

Intermittent pneumatic compression of the calf has proven beneficial as prophylaxis for calf vein thrombosis. To define a possible role for the fibrinolytic system, two studies were performed.Two groups of normal male volunteers aged 18-42 years were rested for one half hour; a control blood sample was drawn and one arm or both legs pumped for one half hour using a pneumatic boot inflated intermittently to 50mm Hg (90 sec. on, 90 sec. off; filling time 60 sec.). A second blood sample was obtained. In group one (arm pumped; antecubital vein sample, same side) the euglobulin lysis time decreased 23% (191 to 147 min., n=13, p=.05). In group two (both legs pumped; simultaneous sample from femoral and antecubital veins) there was a 25% reduction in euglobulin lysis (230 to 172 min., n=16, p=.01) in femoral vein blood and an 18% decrease in antecubital vein blood (229 to 188 min., n=16, p=.04). As expected the effect was most pronounced in the local venous effluent and less noticeable in the systemic circulation due to dilution.The possibility that mechanical compression of the calf veins produces chemical changes that might exert a beneficial effect in preventing venous calf thrombosis is consistent with the data.
Fibrinolytic System and Fibrinolytic Inhibitors in Behcet’s Disease
Authors: Asbeck F. , Meyer-Boernecke D. , van de Loo J. 
Published: May 2019

An increase of the inhibitory potential seems to be the generally accepted cause for the suppression of the fibrinolytic system in Behcet’s disease. To prove this theory, we investigated 5 male patients (31-46 yrs.) suffering from severe Behcet’s syndrome. Additionally, three of them were treated with Stanozolol (1o mg/d) and Phenformin (1oo mg/d) during a period of one year. The following parameters were investigated in detail: Fibrinogen; plasmin (different fibrin plate assays) ; plasminogen, fast reacting antiplasmin, plasmin-antiplasmin complex, alpha2-macroglobulin, C1-esterase inhibitor, alpha1-antitrypsin, antithrombin III (different immunological methods).In all patients, the concentration of fibrinogen and alpha1-antitrypsin were elevated. There were normal concentrations of plasminogen, fast reacting antiplasmin, plasmin-antiplasmin complex, alpha2-macroglobulin, C1-esterase inhibitor, and antithrombin III. Using the venous occlusion technique, a marked reduction of the in-vivo activation of the fibrinolytic system could be demonstrated. - During therapy with Stanozolol and Phenformin, a high fibrinolytic response was induced by venous occlusion. The analysis of the different inhibitors, however, could not explain this phenomenon. An increased production or release of vessel activator(s), therefore, seems to be the mechanism of fibrinolysis induction by anabolic steroids and Phenformin.
Platelet Aggregation in Heart Disease
Authors: Oversohl K. , Theiss W. , So C.S. , Seidl K.F. 
Published: May 2019

Increased platelet adhesion and aggregation has been reported in patients suffering from rheumatic valvular heart disease and from atherosclerotic heart disease. We therefore measured spontaneous aggregation “PAT III” (Breddin) and ADP-induced platelet aggregation (Born) in 141 patients who underwent cardiac catheterization. There were 50 patients with coronary heart disease, 41 with valvular heart disease, 18 with cardiomyopathy; 32 with normal findings at catheterization served as control group.In comparison to controls, patients with coronary heart disease had significantly increased aggregation. Subdivision into 1, 2, or 3 vessel disease revealed no significant differences. Patients with valvular heart disease also had significantly increased aggregation. This appears to be particularly the case after valvular grafting. Cardiomyopathies were not associated with increased platelet aggregation.
Experimental Study of a platelet Antiaggregating Agent - Application to Ticlopidine
Authors: Stoltz J.F. , Verry M. , Farge B. 
Published: May 2019

The authors consider the various methods suitable for in vivo study of the anti-aggregating properties of a new drug - Ticlopidine :- study of photometric ADP-induced aggregation and screen filtration pressure in vivo in the rabbit treated per os for 5 days with doses of 25 and 50 mg/kg/d. This gave average inhibitions of 30% and 45% respectively.- study of circulating platelet aggregates using the method of Wu and Hoak after continuous infusion of ADP or of thrombin. The principle of the method involves definition of an aggregation index : the ratio between the platelet counts in the two specimens (EDTA + formol 1 % + EDTA alone).The average results showed : control group index 0.9 -after infusion of ADP 0.57- after infusion of ADP under the influence of Ticlopidine (50 and 100 mg/kg/d) 0.66 to 0.78.- the mechanism of action of the drug was studied using crossed aggregation experiments and by the study of interference with ionised or ionisable groups of the platelet membrane (isotope method, electrophoresis in liquid phase).In parallel with these experiments, studies in vivo in the rabbit and in patients (obliterative arterial disease, Raynaud’s syndrome) are in progress : interference with membrane groups, rheological properties (viscosity, rouleau formation, erythrocyte deformability) and biochemical properties (erythrocyte glycolysis enzymes).
Measurement of Amount of Invaginated Membrane in Mammalian Platelets by Osmotically-Induced Spherocyte Formation
Authors: Milton John G. , Frojmovic M.M. 
Published: May 2019

Invaginated membrane of the surface-connected canalicular system (SCCS) of the resting platelet can be potentially externalized. We have estimated the SCCS surface area by carefully swelling platelets in hypotonic media. Platelets were osmotically stressed by either interfacing a drop of platelet-rich plasma (PRP) with distilled water on a siliconized glass slide or directly in a test tube by careful additions of 60-80% by volume water. Surface areas of the platelets were estimated from a cinematographic analysis of freely rotating platelets. Within five minutes of the addition of water, large smooth spheres (spherocytes) are formed. Soluble, cytoplasmic lactate dehydrogenase activity is not released and visible membrane damage as estimated from dark-field microscopy observations does not occur for at least one hour. The mean value of the spherocyte diameters was 3.9 ± 0.6 um (3 human donors) and did not change over 5 - 60 minutes. It is estimated that the volume of the spherocyte is ~550% greater than that of the original disc and that the surface area has increased by ~300%. Similar results were obtained for rabbit platelets.Since platelet swelling induced osmotically has been shown to yield large spheres with the disappearance of SCCS (J.G. White, personal communication), it is concluded that: 1) the SCCS of the resting platelet can be easily externalized, and 2) osmotic spherocyte formation allows a quantitative estimation of the SCCS surface area.
The Effect of Sulfinpyrazone and Aspirin on the IVY Template Bleeding Time
Authors: Stuart R. K. , Barnett H.J.M. 
Published: May 2019

The Canadian Stroke Study has afforded us an opportunity to study the effect of sulfinpyrazone 800 mg daily, aspirin 1200 mg daily, both drugs together, and a placebo on the Ivy template bleeding time. Patients with transient cerebral ischemic attacks were randomized to one of the treatment groups and studied before and during treatment.In 352 patients studied pre-drug, the mean bleeding time was 5.02 ± 2.38 (± 1 SD) minutes. Aspirin significantly prolonged the bleeding time (p=.001). Sulfinpyrazone alone had no effect on the bleeding time. In patients receiving both drugs, the effect was no greater than that of aspirin alone. 51Cr platelet survival studies have been completed in 47 patients during treatment. The mean of 8.4 days was similar to the mean in 17 normal controls(8.3 days). However, analysis by treatment groups remains to be done.
Effects of Lipid-Lowering Drugs Upon Fasting-Induced Platelet Aggregation
Authors: Gjesdal K. 
Published: May 2019

During fasting, plasma free fatty acid (FFA) concentration increases, correlating with an increase in the percentage of venous reversible platelet aggregates (Gjesdal et al, Thromb. Haemostas. 36, 325, 1976). In the present study 20 healthy males, who had fasted for 72 hours, received either 1 g of sodium salicylate (SS) or 0.2 g of a nicotinic acid analogue (NAA) orally. Blood was collected before, and 1/2, 1 and 2 hours after drug intake. FFA was assayed by titration and platelet aggregates according to Wu and Hoak (Lancet 2, 924, 1974).After SS, mean FFA concentration was reduced (p<0.01) from 1.87 to 1.34 (1/2h), 1.49 (lh) and 1.66 (2h) mmol/1, whereas NAA resulted in a reduction (p<0.01) from 1.43 to 0.94 (l/2h), 0.65 (lh) and 0.67 (2h) mmol/1. Concomitantly, platelet aggregate percentage decreased transiently (nat significantly) from mean values of 38% (SS group) and 32% (NAA group) to minimum levels of 21 and 23% respectively. During lipolysis inhibition, no significant correlation was found between FFA concentration and aggregate percentage, suggesting that other factors than FFA then had the greater influence upon reversible platelet aggregation.