bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation
Authors: Bergqvist D , Arfors K-E 
Published: July 2018

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.
Isolation and Characterization of Heparin from Human Mastocytoma Tissue
Authors: Thunberg L , Höök M , Lindahl U , Abildgaard U , Langholm R 
Published: July 2018

SummaryPolysaccharide was isolated from human spleen mastocytoma by proteolytic digestion, precipitation with cetylpyridinium chloride, digestion with chondroitinase ABC, and ion-exchange chromatography on DEAE-cellulose. The final product (0.7 mg per g of starting material, MW 8000) behaved like standard heparin on ion-exchange chromatography and on electrophoresis, and contained D-glucuronic acid, L-iduronic acid, D-glucosamine and sulfate in the proportions expected for heparin.Affinity chromatography on antithrombin-Sepharose separated a distinct high-affinity fraction (4–5% of the total material). Structural analysis of this fraction showed that about 10% of the D-glucosamine residues were N-acetylated, the remainder N-sulfated.The anticoagulant activity of the isolated heparin was 71 B.P. units per mg (whole-blood system), or 30 units per mg (antithrombin and chromogenic substrate). 205 and 10–15 units per mg (chromogenic assay) were found for high and low affinity fractions, respectively. These results demonstrate conclusively the occurrence of heparin in a human tissue.
Clinical and Biological Activity of the Antiplatelet Agent Suloctidil in Treatment of Idiopathic Recurrent Vein Thrombosis (I.R.V.T.)
Authors: Moriau M , Beys C Col-De , Pardonge E , Ferrant A 
Published: July 2018

SummaryA double blind cross over study with suloctidil (Sulocton, Continental Pharma) and placebo was carried out for 6 months in 31. patients with idiopathic recurrent vein thrombosis. They were previously unsuccessfully treated with vitamin K antagonists (VKA) (18 patients) or acetylsalicylic acid (ASA) (13 patients) combined or not with a fibrinolysis activator (theophylline nicotinate).Clinical features, ultrasonic venous flow and biological parameters were controlled monthly during the 6 month treatment. Relevant improvement of clinical, ultrasonic and biological parameters was only observed under suloctidil therapy: during placebo administration 12 patients developed new thrombotic events complicated in 2 by pulmonary embolism while none occurred under suloctidil therapy.
Comparative Study of the Activity of High and Low Molecular Weight Urokinase in the Presence of Fibrin
Authors: Samama M , Castel M , Matsuo O , Hoylaerts M , Lijnen H R 
Published: July 2018

SummaryThe fibrinolytic or thrombolytic activity of low molecular weight urokinase (LMW-UK) and high molecular weight urokinase (HMW-UK) is not significantly different when measured in a bovine fibrin plate method, in a circulating plasma system containing a 125I-labelled human fibrin clot, or on 125I-fibrin films in culture plates using normal or α2-antiplasmin depleted human plasma.In a human fibrin plate method however HMW-UK was found to be more active than LMW-UK. In a purified system on human 125I-fibrin films the activation of native or modified human plasminogen by HMW-UK was also found to be more effective than by LMW-UK.Using a clot lysis test system we did not observe a different inhibition of LMW-UK and HMW-UK upon incubation in human plasma. This is in contrast with previous reports that HMW-UK is inhibited more rapidly in human plasma than LMW-UK.In a purified system the inhibition rate of LMW-UK and HMW-UK by α2-antiplasmin is the same (rate constants at 25ΰC of 167 ± 9 M−1s−1 and 171 ± 5 M−1s−1 respectively).The clinical trials available at present used doses of urokinase which were in excess of those required to obtain a maximal fibrinolytic effect. This might explain why in these trials no difference was observed between the thrombolytic effect of LMW-UK and HMW-UK, while in vitro HMW-UK appeared to be more effective. However, one should always be careful to extrapolate in vitro observations as such to the in vivo situation encountered during thrombolytic therapy.
An Enhancing Effect of Poly-Lysine on the Activation of Plasminogen
Authors: Allen R A 
Published: July 2018

SummaryThis study demonstrates that poly-lysine mimics the cofactor (enhancing) function of fibrin that is seen in tissue activator-induced plasminogen activation. Additionally, and in contrast to fibrin, poly-lysine exhibited an enhancing effect on low molecular weight (and not high molecular weight) urokinase-induced plasminogen activation.A mechanism is proposed for this enhancement that involves the rendezvous and local concentration of plasminogen and plasminogen activator molecules on the lysine polymer. All components were able to bind to immobilized poly-lysine making the proposed machanism feasible. It was possible to elute the activators and mini-plasminogen by high salt (1 M NaCl), in contrast to Glu-plasminogen and plasmin which required 1 M lysine for elution, suggesting specific binding involving lysine binding sites.The enhancing effect was specific for poly-D- and L-lysine and poly-L-ornithine, which has a similar structure. The use of poly-lysine can lead to a better standardization and increased sensitivity of indirect two-step assays for plasminogen activators employing synthetic chromogenic substrates.
Synthesis of Thromboplastin Protein by a Murine Macrophage-Like Cell Line
Authors: Lyberg T , Hetland Ø , Prydz H 
Published: July 2018

SummaryThe established murine macrophage cell line J-774.1 responds to endotoxin with synthesis of thromboplastin apoprotein. The response develops in the absence of added lymphocytes and there is no increased responsiveness in cocultures of J-774.1 cells and BALB/c lymphocytes. J-774.1 cells therefore do not depend on lymphocyte cooperation for their response to endotoxin.
The Amidolytic Activity of the SK-Plasminogen Complex Is Enhanced by a Potentiator which Is Generated in the Presence of Vascular Plasminogen Activator - Role of Fibrin Degradation Products
Authors: Soria J , Soria C , Bertrand O , Dunn F , Samama M , Bachmann F 
Published: July 2018

SummaryIn the presence of an excess of streptokinase (SK) the amidolytic activity of the plasminogen-SK complex on chromogenic substrates is 12% lower in serum than in the corresponding plasma. However, in subjects in whom venous stasis lead to a shortening of the euglobulin lysis time to less than 60 min (high responders), the amidolytic activity of the plasminogen-SK complex in serum was 60% higher than in the corresponding plasma. Attempts to find alterations of the plasminogen molecule itself which would account for the enhanced activity in high responder serum were negative. No free plasmin was present and the plasminogens isolated from plasma and serum before and after venous stasis had the same amidolytic activity as glu-plasminogen in the presence of an excess of SK. N-terminal analysis of these four plasminogens revealed in each instance glutamic acid.The enhancement of the amidolytic activity of the SK-plasminogen complex in serum of high responders (potentiator activity) could be reproduced by adding purified tissue plasminogen activator (TA) to native blood before clotting, but not if TA was added to plasma or to prestasis serum. Removal of fibrin degradation products from poststasis serum resulted in the disappearance of potentiator activity. These experiments suggest that fibrin degradation products, generated during clotting in the presence of vascular or tissular plasminogen activator act as a potentiator of the amidolytic activity of the plasminogen SK-complex.
Predicting the Dose of Warfarin for Therapeutic Anticoagulation
Authors: Sharma N K , Routledge P A , Rawlins M D , Davies D M 
Published: July 2018

SummaryThe validity of a previously described technique for predicting warfarin requirements based on the anticoagulant response to a fixed loading dose was assessed prospectively in 57 patients. There was a close relationship between the predicted and initially observed daily warfarin dose required to maintain the patient within the therapeutic range for anticoagulation. The significant relationship between predicted and observed maintenance dose persisted at 4 and 12 weeks although it decreased with increasing time.The relationship between observed and predicted maintenance requirement of warfarin was not affected by the concomitant use of intermittent intravenous injections of heparin when 9 hr was allowed to elapse between the previous dose of heparin and the thrombotest estimation on which the prediction was based.It is concluded that the method is valuable in predicting an individual’s warfarin requirement, although it does not obviate the need for regular monitoring of anticoagulant control.
Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis
Authors: Thomas D P , Merton Rosemary E , Barrowcliffe T W , Thunberg L , Lindahl U 
Published: July 2018

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.
Acyl-Enzymes as Thrombolytic Agents in a Rabbit Model of Venous Thrombosis
Authors: Smith R A G , Dupe R J , English P D , Green J 
Published: July 2018

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.
The Effect of Bovine Lung Heparin on Normal Human Platelets as Measured by Electronic Particle Size Analysis
Authors: McLean Margaret R , Hause Lawrence L 
Published: July 2018

SummaryThe response of normal human platelets to treatment with bovine lung heparin was evaluated using electronic particle size analysis and aggregometry. Samples for electronic particle size analysis were obtained both before and after the addition of heparin to platelet-rich plasma (PRP). The number of single platelets decreased significantly after the addition of heparin to PRP obtained from 22 individuals. This decrease averaged 18% in 19 samples which did not show a significant increase in transmittance and was at least 70% in 3 samples which showed a significant increase in transmittance. The size distribution of single platelets was not significantly altered. In addition, electron microscopic examination revealed that platelets treated with heparin are activated.
A Possible Method to Control Prolongations of Bleeding Time under Antiplatelet Therapy with Ticlopidine
Authors: Thébault J , Blatrix C , Blanchard J , Panak E 
Published: July 2018

SummaryThe interactions of oral and i.v. administrations of corticosteroids with the effects of ticlopidine were studied, in a search for an antidote for possible excessive prolongations of bleeding time induced by antiaggregating agents. Indeed, the results show that an i.v. injection of methylprednisolone or an oral treatment with prednisolone counteract the prolongation of bleeding time but do not interfere with the inhibition of platelet aggregation brought about by ticlopidine. This could be ascribed to a vasoconstrictive effect of corticosteroids, possibly through reduction of vascular prostacyclin release. If this mode of action was confirmed, this useful finding would essentially apply to ticlopidine, but not to cyclooxygenase inhibitors such as aspirin which, by themselves, abolish prostacyclin production.
The Intrinsic Fluorescence of Human Fibrinogen and Its Fragments D and E
Authors: Kowalska M A , Cierniewski C S 
Published: July 2018

SummaryThe tryptophan fluorescence of fibrinogen and its final degradation products - fragment D and E - were compared. Fibrinogen and its derivatives exhibit identical emission and excitation spectra. Their fluorescence intensity is influenced to a different extent by pH titration and temperature.Our studies showed that tryptophan residues of core fragments D and E are much more exposed to quenching effects of acrylamide and ions than intact fibrinogen, which may be caused by conformational changes occurring over the domains during plasmin digestion of fibrinogen molecule.
Kinetics of the Reaction Between Urokinase and an Inhibitor of Fibrinolysis from Placental Tissue
Authors: Christensen Ulla , Holmberg L , Bladh B , Åstedt B 
Published: July 2018

SummaryThe interaction of urokinase (EC 3.4.21.31) and a protein proteinase inhibitor of fibrinolysis partially purified from placental tissue, which inhibits urokinase but not plasmin, was investigated. The preparations of the inhibitor contained no other known proteinase inhibitors. It was found that a 1:1 complex is formed and that the reaction proceeds as a second order, one step process, the association rate constant of which is 4.5 106 M−1 S−1 at pH 8.4, 37° C and 3.0 106 M−1 S−1 at pH 7.3, 37° C. The binding is very tight, the dissociation constant of the inhibitor-urokinase complex was estimated to be Ki≦10−11 M.
Homo- and Heterogeneous Forms of Human Factor VIII
Authors: Vukovich Th Chr 
Published: July 2018

SummaryIn order to determine the molecular size of human F VIII as found in fresh plasma and as found in fresh-frozen plasma and in cryoprecipitate and to study the relationship of the factor-related properties, namely F VIII:C, F VIIIR:Rcof and F VIIIR:Ag to F VIII, the factor’s elution pattern on Sephacryl 1000 was investigated. When fresh plasma was chromatographed on this gel, F VIII eluted in a single sharp peak with all three F VIII-related activities appearing in the separation range of the gel column. The molecular weight of F VIII was calculated to be higher than 8 × 105. When fresh-frozen plasma was chromatographed on this gel, the elution pattern was identical to that of fresh plasma with the single exception that in several samples F VIII eluted in a broader peak tailing to higher molecular forms. When cryoglobulin fraction of fresh-frozen plasma was chromatographed, F VIII showed distinct heterogenicity in the elution pattern with respect to molecular size and relationship to the F VIII-related properties. Chelation of the endogenous plasma Ca-ions by citrate was found to have no influence on the factor’s elution pattern.
A Kinetic Method for Characterization of Heterogenous Fibrinogen and Its Application to Fibrinogen Grand Rapids, a Congenital Dysfibrinogenemia
Authors: Higgins D L , Lewis S D , Penner J A , Shafer J A 
Published: July 2018

SummaryA kinetic analysis was developed to determine the steady state kinetic parameter kcat/KM for the thrombin-catalyzed release of FPA from abnormal and normal fibrinogen in mixtures of the two. Such mixtures are likely to comprise the fibrinogen of individuals with congenital dysfibrinogenemia. The analysis was used to characterize fibrinogen Grand Rapids, a new congenital dysfibrinogenemia. It indicated that fibrinogen from affected individuals was composed of normal and abnormal fibrinogen in roughly equal amounts, and that the value of kcat/KM for the thrombin-catalyzed release of FPA from the fibrinogen variant was 77fold lower than that for the release of FPA from the normal fibrinogen. In separate studies, fibrinogen Grand Rapids was found to exhibit a reduced clottability. Additionally, affected individuals appeared to have plasma fibrinogen concentrations which were about one-third the normal value.
Rheo-Optical Shape Analysis of Human Blood Platelets
Authors: Affolter Hubert , Pletscher Alfred 
Published: July 2018

SummaryAlterations in rheo-optical signals obtained from suspensions of human blood platelets treated in various ways (drugs, storage in the cold, stirring, etc.) were monitored. A self-normalizing instrument measuring scattered light and relative amplitude of rapid oscillation of light intensity (noise level) at different angles was used. The following results have been obtained: 1. The light scattered at an angle of 40° was decreased with considerable selectivity by pseudopod formation, if aggregation was inhibited. 2. The noise levels at 0° and 40° were selectively diminished by the transition from the discoid to the spheroid shape of the platelets. 3. At 40°, but not at 0°, the noise level responded without delay and was not influenced by aggregate formation. Using this method alterations in platelet form, i.e. spheroid transformation and pseudopod formation, can be specifically and continuously monitored. In addition, the noise level at 40° is a definite quantitative measure of the discoid state. This allows the determination of platelet activation without manipulations such as changes in stirring rates or addition of drugs.
The Effect of Oral Contraceptives on Coagulation and Fibrinolytic Parameters in the Chinese – A Prospective Study
Authors: Wong Vivian , Chan T K , Chan Vivian , Tso S C , Todd D , Ma H K 
Published: July 2018

SummaryThirty-two Chinese and 7 Caucasians were studied prospectively for 12 months for the effects of oral contraceptives (OC) on certain coagulation and fibrinolytic parameters. In both ethnic groups there was an increase in α1 antitrypsin level. There was no significant change in antithrombin III concentration measured either by radioimmunoassay (At-III-RIA) or chromogenic assay (anti Xa-chromogenic) in the Chinese, but a significant decrease in anti Xa-chromogenic at 7 months and At-III-RIA at 12 months in the Caucasians. Also, α2 plasmin inhibitor (α2PI) levels were unchanged in the Chinese but a significant increase occurred in the Caucasians at 12 months. Enhanced fibrinolytic response to venous occlusion was demonstrated in the Chinese at 12 months but not in the Caucasians.
Common Units for Clotting Factors Assayed Against Different Standards
Authors: North W R S , Stirling Y , Meade T W 
Published: July 2018

SummaryThere are no generally accepted units for clotting factors except factor VIII. Results are usually expressed as percentages of the standards used in the assays and standards vary in their potency. Over a six year period, factors V, VII and VIII were measured in over 3000 participants in the Northwick Park Heart Study. Six different standards had to be used. For comparative purposes, all results were expressed in terms of the first standard (71/11). This paper describes how appropriate conversion values were derived. Three different methods were compared. One consisted of the assay of each standard against its replacement. Another was based on the use of a reference plasma spanning the use of two successive standards. The third was a population-based, or epidemiological method using the data from all the participants in the study. This method is based on the assumption that results would be the same in comparable groups of study participants. In order to ensure comparability, personal characteristics which affect clotting factor levels, such as age and degree of obesity, were taken into account. The three methods gave similar results but the population method was, in general, the most satisfactory for factor VIII as well as factors V and VII, and has been adopted for routine use.
Alteration of Platelet Aggregation by Cigarette Smoke and Carbon Monoxide
Authors: Mansouri Ali , Perry Carol A 
Published: July 2018

SummaryPlatelet aggregation with epinephrine, adenosine diphosphate and arachidonic acid was studied in the presence of cigarette smoke and carbon monoxide. It is shown that cigarette smoke inhibits the arachidonic acid induced platelet aggregation as well as the second phase of epinephrine induced aggregation. The adenosine diphosphate induced platelet aggregation is not significantly affected by cigarette smoke. Carbon monoxide causes similar alterations in platelet aggregation. These results suggest that cigarette smoke inhibits platelet aggregation. This aggregation inhibition is due to the presence of carbon monoxide.