bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic Study of the Effect of Heparin on the Amidase Activity of Trypsin, Plasmin and Urokinase
Authors: Yomtova V M , Stambolieva N A , Blagoev B M 
Published: July 2018

SummaryIt was found that the effect of heparin on the amidase activity of urokinase (E C 3.4.21.31), plasmin (E C 3.4.21.7) and trypsin (E C 3.4.21.4) depended on the substrate used. No effect of heparin on the amidase activity of urokinase and trypsin was observed when Pyro Glu-Gly-Arg-p-nitroanilide (S-2444) and α-N-acetyl-L-lysine-p-nitroanilide (ALNA) were used as substrates. Heparin acted as a uncompetitive inhibitor of trypsin (Ki = 1.2×10-6 M), plasmin (Ki = 4.9×10-6 M) and urokinase (Ki = l.0×10-7 M) when Bz-Phe-Val-Arg-p-nitroanilide (S-2160), H-D-Val-Leu-Lys-p-nitroanilide (S-2251) and plasminogen, respectively, were used as substrates. These results, as well as the data obtained by studying the effect of the simultaneous presence of heparin and competitive inhibitors suggest that although heparin is not bound at the active center of these enzymes, it may influence the effectivity of catalysis.
The Action of Thrombin on Modified Fibrinogen
Authors: Osbahr A J 
Published: July 2018

SummaryThe modification of canine fibrinogen with citraconic anhydride modified the ε-amino groups of the fibrinogen and at the same time generated additional negative charges into the protein. The addition of thrombin to the modified fibrinogen did not induce polymerization; however, the fibrinopeptide was released at a faster rate than from the unmodified fibrinogen. The physical properties of the citraconylated fibrinogen were markedly altered by the modification of 50-60 lysine residues in one hour. A modified fibrinopeptide-A was released by thrombin from the modified fibrinogen and was electrophoretically more anionic than the unmodified fibrinopeptide-A. Edman analysis confirmed the modification of the lysine residue present in the peptide. The rate of removal of citraconylated fibrinopeptide-A from modified fibrinogen by thrombin was 30 to 40 percent greater than the cleavage of unmodified fibrinopeptide-A from unmodified fibrinogen. However, the modification of 60 or more lysine residues in the fibrinogen produced a decrease in the rate of cleavage of citraconylated fibrinopeptide-A. The results suggest that additional negative charge in the vicinity of the attachment of fibrinopeptide-A to canine fibrinogen aids in the removal of the peptide by thrombin.
Warfarin and Heparin Interaction with Prostacyclin-Like Activity Generated by Arterial Wall in the Rat
Authors: Doni M G , Piva E 
Published: July 2018

SummaryA study was performed to evaluate the hypothesis that heparin opposes uncontrolled PGI2 production by vessels due to thrombin generation. We treated animals with warfarin, an inhibitor of liver synthesis of prothrombin and other vit. K-dependent clotting factors. In fact, if thrombin is presumed to be the stimulus for PGI2 production, warfarin should suppress this effect. As warfarin treatment did not affect significantly PGI2-like activity, we conclude that a different hypothesis is necessary to explain the phenomenon. On the other hand, i. p. sodium heparin effectively induced a decrease in PGI2-LA synthesis, whereas s. c. calcium heparin did not significantly influence it.
Plasma Levels of Platelet and Vascular Prostaglandin Derivatives in Children with Sickle Cell Anaemia
Authors: Buchanan George R , Holtkamp Christine A 
Published: July 2018

SummaryPlatelet and vascular endothelial prostaglandin derivatives were measured by radioimmunoassay in the plasma of 39 children with homozygous sickle cell anaemia and 27 control subjects. The levels of both thromboxane B2 and 6-keto-PGF1α, the stable endproducts of platelet and vascular prostaglandin metabolism, were significantly (p <0.001) greater in sickle cell anaemia plasma than in the plasma of the controls. There were no differences in levels of either 6-keto-PGF1α or thromboxane B2 between steady state and vaso-occlusive crisis in the sickle cell patients. Injury to the endothelial lining of blood vessels may occur in sickle cell anaemia as a consequence of contact with the abnormal erythrocytes.
Interaction of β2-Glycoprotein-I with Human Blood Platelets: Influence Upon the ADP-Induced Aggregation
Authors: Nimpf Johannes , Wurm Helmut , Kostner Gerhard M 
Published: July 2018

SummaryThe interaction of β2-glycoprotein-I (β2-G-I), a plasma constituent of unknown function, with blood platelets was studied. The following results were obtained: 1) β2-G-I binds to washed human platelets isolated by centrifugation (WP) at one kind of specific, saturable binding sites. The dissociation constant was found to be approx. 1 × 10−6M.2) In the presence of physiological concentrations of Ca++ (2.5 mM), this specific binding is markedly reduced. Unspecific binding of β2-G-I to platelets, however, is not influenced by Ca++.3) Platelets prepared by gel filtration (GFP), differing in their in vitro aggregability from WP, exhibit no specific binding of β2-G-I. Binding to GFP is also not induced by activation with thrombin, collagen or ADP.4) β2-G-I causes significant alteration of the ADP-induced aggregation of GFP. Aggregation induced by thrombin, collagen, arachidonic acid or PAF-acether, however is not altered by β2G-I.It is suggested, that pelleting during centrifugation causes irreversible rearrangements in the membrane of platelets.
Reduced Prostacyclin Survival After Fasting-Induced Elevation of Plasma Free Fatty Acids
Authors: Goodnight S H , Inkeles S B , Kovach N L , Connor W E 
Published: July 2018

SummaryThe anti-thrombotic effect of prostacyclin (PGI2) may be determined not only by its synthetic rate but also by its subsequent survival in blood. After its release from the vascular wall, prostacyclin binds to plasma albumin which stabilizes the molecule and prolongs its inhibitory effects on platelets. In vitro studies have shown that free fatty acids compete for the same albumin binding sites and may therefore displace PGI2 and substantially shorten its survival. To see if this competition could also occur in vivo, we produced a three-fold rise of plasma free fatty acid concentrations in ten normal volunteers by four days of fasting, which led to a significant reduction in prostacyclin survival as measured by a functional assay based on inhibition of ADP-induced platelet aggregation. The shortening of prostacyclin survival was associated with evidence of increased platelet reactivity as measured by the circulating platelet aggregate ratio test. Diseases that produce marked elevations of free fatty acids such as acute myocardial infarction may also lead to shortened PGI2 survival with potentiation of platelet mediated thrombosis.
Increased Yield of Human Tissue-Type Plasminogen Activator Obtained by Means of Recombinant DNA Technology
Authors: Browne M J , Dodd I , Carey J E , Chapman C G , Robinson J H 
Published: July 2018

SummaryExtra copies of the human tissue-type plasminogen activator (t-PA) gene were introduced into the Bowes melanoma cell line. We obtained a recombinant cell line (TRBM6) which secretes approximately ten-fold more t-PA than the parent cell line. The identity of the plasminogen activator made by the new cell line was confirmed by sizing on sodium dodecyl sulphate polyacrylamide gels and by specific quenching using anti-t-PA antibody. We estimate that the recombinant line produces t-PA at a rate of approximately 3 pg/cell/24 hr and that t-PA accumulates in the harvest medium at a rate of approximately 4000 International t-PA Units/ml/24 hr.
Mouse Trophoblast Cells Are Constitutive Producers of Thromboplastin (Factor III) In Vitro
Authors: Dalaker K , Haug E , Prydz H 
Published: July 2018

SummaryTrophoblasts from murine placenta synthesize thromboplastin in the absence of inducing agents and a functional complement system, nor is the rate or level of synthesis enhanced by inducers. A serum factor which is destroyed/removed by addition of oxalate and subsequent dialysis appears to enhance the ability of trophoblasts to synthesize thromboplastin.
Increased PA-Inhibitor Levels in the Postoperative Period – No Cause-Effect Relation with Increased Cortisol
Authors: Aillaud M F , Juhan-Vague I , Alessi M C , Marecal M , Vinson M F , Arnaud C , Vague P , Collen D 
Published: July 2018

SummaryIt has been reported that the level of PA-inhibitor increases in postoperative patients and on the other hand that glucocorticoids increase the PA-inhibitor level in cell culture. Because surgery is associated with increased plasma cortisol level, a relation between the postoperative increase in plasma cortisol and PA-inhibitor levels was looked for.Blood samples were collected from 8 patients undergoing extensive abdominal surgery, before operation and postoperatively at 2 hr, 4 hr, 24 hr and daily for 7 days. Plasma cortisol and PA-inhibitor were increased 2 hr after surgery, when there was a significant correlation (p <0.05). The maximum increase was at 24 hr and the values fell to normal on day 6. An increase in t-PA related antigen (t-PA R:Ag) and a decrease in euglobulin fibrinolytic activity (EFA) also occurred.In 7 controls 0.25 mg ACTH was given intravenously and blood was collected after ½, 1, 2, 4, 6 hr. Although the increase in plasma cortisol level following ACTH was comparable to that observed after surgery the increase was not associated with significant change in PA-inhibitor level, t-PA R: Ag or EFA.A cause-effect relationship between the increased plasma cortisol and PA-inhibitor level could not be shown. The mechanism of the postoperative increase in PA-inhibitor thus remains unknown.
The Effects of Nicotine on PGI2 Production by Rat Aortic Endothelium
Authors: Bull H A , Pittilo R M , Blow D J , Blow C M , Rowles P M , Woolf N , Machin S J 
Published: July 2018

SummaryThe production of prostacyclin by rat aortic rings was measured following administration of nicotine by a single subcutaneous injection and after continuous subcutaneous infusion over 7 days. Single subcutaneous injections of nicotine at 1, 5, 10 or 20 mg/kg had no effect on prostacyclin production by rat aortic rings in comparison with controls. However, aortic rings obtained after 7 days continuous subcutaneous infusion of 0.54 g/ml of nicotine at the rate of 1 μl per hour produced significantly less prostacyclin than control animals.
A Comparative Study of the Effects of Adrenoceptor Antagonists on Platelet Aggregation and Thromboxane Generation
Authors: Greer I A , Walker J J , McLaren M , Calder A A , Forbes C D 
Published: July 2018

SummaryPlatelet aggregation and thromboxane A2 have been implicated in the pathogenesis of several forms of vascular disease. The aim of this study was to determine the effect of a wide range of adrenoceptor antagonists on platelet aggregation, and thromboxane A2 production, from normal human platelet rich plasma in vitro. Labetalol, pindolol and propranolol inhibited platelet aggregation to collagen in a dose dependent manner. Increasing the concentration of collagen “shifted” the dose response curve to the right. These 3 drugs also significantly inhibited thromboxane A2 generation in response to collagen but not to arachidonic acid. This effect was independent of any inhibitory effect of these drugs on platelet aggregation, and occurred at a drug concentration close to that obtained in vivo. Atenolol, metoprolol, prazosin and timolol were similarly assessed but had no effect on either platelet aggregation or thromboxane A2 generation. This ability of labetalol, pindolol, and propranolol to inhibit platelet aggregation and thromboxane generation, may be of clinical benefit in view of the increasing evidence implicating thromboxane A2 in the pathogenesis of vascular disease.
The Effects of Thromboxane Antagonism on the Transit Time of Platelets Through the Spleen
Authors: Peters A M , Lane I F , Sinclair M , Irwin J T C , McCollum C N 
Published: July 2018

SummaryThe spleen is well-known as a site for platelet pooling, although the mechanisms controlling intrasplenic platelet transit are essentially unknown. We tested the possibility that thromboxane A2 might be involved in this control by measuring intrasplenic platelet transit time in 10 subjects receiving a specific thromboxane A2 receptor antagonist (AH23848B; 70 mg; Glaxo Group Research Ltd), in 10 receiving aspirin (300 mg) plus dipyridamole (75 mg), and in 9 receiving placebo. All doses were administered 3 times daily commencing 4 days prior to transit time measurement.Mean intrasplenic platelet transit time was measured by monitoring the kinetics of equilibration of 111In radiolabelled platelets between blood and spleen following intravenous injection. There was no difference between the mean transit time in the 3 groups of subjects, lending no support to the hypothesis that thromboxane A2 is involved in the control of platelet traffic through the spleen.
Endothelial Cells Degrade Extracellular Matrix Proteins Produced In Vitro
Authors: Laug Walter E , Weinblatt Mark E , Jones Peter A 
Published: July 2018

SummaryBovine aortic endothelial cells (BAEC) were grown on extracellular matrices produced by vascular smooth muscle cells or fetal bovine endothelial cells. The glycoprotein components of these complex substrates were degraded through activation of the serum zymogen plasminogen to plasmin, as well as by a plasmino- gen independent protease(s). The plasminogen independent enzyme might be a protease with elastolytic activity since the BAEC digested elastin present in smooth muscle cell derived matrices. The cells also displayed collagenolytic activity on both types of matrices.The addition of the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) (10−7 M) to the culture medium enhanced considerably the plasminogen activator and collagenolytic activities elaborated by BAEC resulting in an increased degradation rate of matrix glycoprotein and collagen components, whereas the elastolytic activity remained unaffected. Dex- amethasone (10−7 M), although suppressing plasminogen activator (PA) production by BAEC, did not alter their elastolytic activity allowing the cells to degrade the glycoprotein components of the matrices at an unchanged rate. The collagenolytic activity of the BAEC remained unaffected by dexamethasone.These studies demonstrate that BAEC elaborate different proteolytic enzyme activities allowing them to degrade various components of extracellular matrices. These enzymatic activities may be modulated by certain agents thus changing the degradative capabilities of the BAEC.
On the Significance of Antithrombin-III, α2-Macroglobulin, α2-Antiplasmin, Histidine-Rich Glycoprotein, and Protein C in Patients with Acute Myocardial Infarction and Deep Vein Thrombosis
Authors: Gram Jørgen , Jespersen Jørgen 
Published: July 2018

SummaryIn a longitudinal study the plasma levels of antithrombin-III, α2-macroglobulin, α2-antiplasmin, histidine-rich glycoprotein, and protein C were followed in two groups of patients with acute myocardial infarction (AMI), one with and one without deep vein thrombosis (DVT). None of the sequentially studied periods revealed significant differences between the two groups of patients. However, small but consistently higher levels of histidine-rich glycoprotein in patients with DVT suggested the existence among patients submitted for myocardial infarction of a subgroup with increased thrombophilic potential. It was concluded that the inhibitors studied are of little value as possible indicators of the presence of DVT at early stages of the disease when clinical signs are absent and when antithrombotic prophylaxis should preferably be initiated.
Prevention of Arterial and Pulmonary Embolism by Oral Anticoagulants in Patients with Dilated Cardiomyopathy
Authors: Kyrle P A , Korninger C , Gössinger H , Glogar D , Lechner K , Niessner H , Pabinger I 
Published: July 2018

SummaryThe incidence of arterial embolism (AE) and pulmonary embolism (PE) during treatment with oral anticoagulants (OA) or without OA therapy was studied in 38 patients with dilated cardiomyopathy (DCMP). AE/PE occurred in 17 patients (44.7%) before initiation of OA treatment. The severity of DCMP was a risk factor for AE/PE, but not the presence of atrial fibrillation or intracardial thrombi. No AE/PE episodes occurred during the period of OA therapy. No major bleeding complications were seen, probably due to the moderate intensity of OA therapy (therapeutic range 5-15% Thrombotest® [TT], 2.1-4.8 International Normalized Ratio [INR], median TT value 11%, median INR 2.6). Recurrence of AE was observed in 4 of 5 patients in whom treatment with OA had been discontinued.
Equal Antiplatelet Effects of Aspirin 50 or 324 mg/Day in Patients After Acute Myocardial Infarction
Authors: De Caterina R , Giannessi D , Boem A , Bernini W , Battaglia D , Michelassi C , Dell’Amico F , L’Abbate A , Patrignani P , Patrono C 
Published: July 2018

SummaryThis study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 ± 22% and + 69 ± 20%, mean ± S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 ± 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 ± 2 and 99 ± 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses <0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.
Quantitative Assessment of Soluble Fibrin in Plasma by Affinity Chromatography – A Comparative Study with desAA-Fibrin, desAABB-Fibrin and Fibrinogen
Authors: Thiel Wilfried , Delvos Ulrich , Müller-Berghaus Gert 
Published: July 2018

SummaryA quantitative determination of soluble fibrin in plasma was carried out by affinity chromatography. For this purpose, desAA-fibrin and fibrinogen immobilized on Sepharose 4B were used at the stationary side whereas batroxobin-induced 125I-desAA-fibrin or thrombin-induced 125I-desAABB-fibrin mixed with plasma containing 131I-fibrinogen represented the fluid phase. The binding characteristics of these mixtures to the immobilized proteins were compared at 20° C and 37° C. Complete binding of both types of fibrin to the immobilized desAA-fibrin was always seen at 20° C as well as at 37° C. However, binding of soluble fibrin was accompanied by substantial binding of fibrinogen that was more pronounced at 20° C. Striking differences depending on the temperature at which the affinity chromatography was carried out, were documented for the fibrinogen-fibrin interaction. At 20° C more than 90% of the applied desAA-fibrin was bound to the immobilized fibrinogen whereas at 37° C only a mean of 17% were retained at the fibrinogen-Sepharose column. An opposite finding with regard to the tested temperature was made with the desAABB-fibrin. Nearly complete binding to insolubilized fibrinogen was found at 37° C (95%) but only 58% of the desAABB-fibrin were bound at 20° C. The binding patterns did not change when the experiments were performed in the presence of calcium ions. The opposite behaviour of the two types of soluble fibrin to immobilized fibrinogen at the different temperatures, together with the substantial binding of fibrinogen in the presence of soluble fibrin to insolubilized fibrin in every setting tested, devaluates affinity chromatography as a tool in the quantitative assessment of soluble fibrin in patients’ plasma.
Enhanced “In Vitro“ Release of Platelet α-Granules After Acute Myocardial Infarction (AMI)
Authors: Pengo V , Boschello M , Prandoni P , Schiavon R , Bellotto F , Schivazappa L , Dalla Volta S 
Published: July 2018

SummaryIn vivo platelet activity was studied in 58 patients with AMI on admittance to the Coronary Care Unit, in 48 of these patients after 1 week, in 30 after 1 month and in 24 patients after 6 months. Patients were carefully selected and excluded if they had associated diseases known to increase platelet activity. In vivo activation was studied by evaluating the plasma concentration of beta-thromboglobulin (β-TG) and platelet factor 4 (PF4) in the same blood sample. On admittance (x = 58.5) and on day 7 (x = 52.9) β-TG values were significantly higher than those obtained in the control group (x = 29). β-TG values were moderately elevated after 1 month (x = 37.7) and then returned to values similar to those of the control group after 6 months (x = 27.9). The simultaneous assessment of PF4 shows a β-TG/PF4 ratio indicative for in vitro release (≤2.5) in many patients on days 1 and 7. Moreover, the β-TG/PF4 ratio in patients with AMI tends towards 2 when β-TG values are high. These results may indicate a greater tendency to an in vitro platelet release in the acute phase of AMI.
Increased Tissue Factor Activity Generation In Vitro by Canine Blood Leukocytes Associated with Allogeneic Kidney Transplantation and Rejection
Authors: Rothberger Henry , Meredith Jesse , Mutton Tom , Brown Jeffery , McGee Maria P 
Published: July 2018

SummaryUsing a canine model, leukocyte populations enriched for monocytes and lymphocytes were isolated from blood during three week periods after kidney allotransplantation corresponding to episodes of acute rejection. Relative to controls, these cells incubated in vitro for five hours were found to generate increased amounts of PCA (procoagulant activity) characterized as tissue factor, the extrinsic clotting pathway activator. Controls included comparable blood leukocyte populations isolated from kidney autograft recipients and healthy animals. Differences in results for these two control groups were insignificant. These contrasts observed between allografted animals and controls demonstrate that leukocyte PCA generation is stimulated by the allogeneicity of histoincompatible kidneys rather than by direct effects of organ transplantation or non-specific postoperative effects. Results of in vitro transfer experiments provide evidence that cellular stimulation or induction in vivo accounted for the PCA increases observed. Stimulation of leukocyte tissue factor generation as a consequence of allogeneic kidney transplantation may in part acccount for coagulopathies and fibrin deposition during kidney rejection.
High Levels of Plasma Protein C in Nephrotic Syndrome
Authors: Pabinger-Fasching I , Lechner K , Niessner H , Schmidt P , Balzar E , Mannhalter Ch 
Published: July 2018

SummaryIn patients with severe nephrotic syndrome determinations of plasma protein C : Ag levels (8 patients: 5 adults, 3 children) and protein C activity (3 out of 8 patients) revealed significantly elevated plasma protein C concentrations. Furthermore we observed a significant inverse correlation of protein C : Ag to AT III : Ag levels. No protein C : Ag could be detected in the urine of two patients studied. We conclude from our data, that changes of plasma protein C do not contribute to the high thrombotic tendency in nephrotic syndrome.