Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour cell induced platelet aggregation (TCIPA) may facilitate haematogenous tumour metastasis. In this study of the aggregatory responses of human platelets to human tumour cell lines, we have found two distinct mechanisms of TCIPA. Colon carcinoma lines Colo 205 and Colo 397 produced TCIPA which was dependent upon thrombin generated through the activation of clotting factor VII, consistent with the expression of tissue factor activity by these cells. This mechanism was calcium dependent and was partially mediated by platelet ADP release as it was inhibited by apyrase. A uterine carcinosarcoma line (Colo 526) produced TCIPA by a novel mechanism which was dependent upon calcium, but was independent of thrombin generation and of the presence of plasma proteins, indicating that this aggregatory response is initiated by a direct platelet-tumour cell interaction.
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PMID:Plasma-dependent and -independent mechanisms of platelet aggregation induced by human tumour cell lines. 362 45

An anticoagulant activity was identified and isolated from the leaves of a West African plant, Aspilia africana by gel filtration on Sephadex G-100. The anticoagulant factor had an apparent molecular weight of approximately 60,000 d. Upon incubation with plasma, it prolonged the partial thromboplastin time, prothrombin time, thrombin and reptilase time. The factor decreased the fibrinogen content of plasma as well as the activity of coagulation factors V, VIII and IX but not factor VII, X or XI activities. After incubation with fibrinogen, the thrombin clotting time was prolonged and the quantity of clottable fibrinogen reduced. The action on fibrinogen was characterized by sequential lytic breakdown of the A-alpha-chain and B-beta-chain, the gamma-chain being lysed last, after prolonged incubation. Benzamidine, Epsilon aminocaproic acid or soybean trypsin inhibitor did not impede lysis.
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PMID:Studies on the anticoagulant action of Aspilia africana. 366 Mar 50

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII. 368 50

The overall generation and inhibition of human factor Xa have been studied in pure systems and plasma to determine the kinetic characteristics of inhibition during factor Xa generation. Generation curves were measured amidolytically in a pure system containing factor X and antithrombin, which was activated with the factor X-activating enzyme of Russell's viper venom (RVV-X). The measured change in factor Xa level with time was fitted to a 3-parameter 2-exponential model to determine apparent first-order rates of inhibition. With antithrombin at 4.5 microM, the inhibition rate constant thus obtained was very close to the known rate of inhibition of exogenous enzyme. Factor Xa generation curves were also analyzed in plasma; however, to reduce interference in the assay of thrombin, congenitally prothrombin-deficient plasma was used containing 0.5 microM D-Phe-Pro-Arg-chloromethylketone. In plasma, factor Xa generated in the presence of phospholipid and Ca2+ ions by RVV-X, factor IXa, or tissue factor was inhibited more slowly than exogenous enzyme. The reduction was particularly severe with tissue factor activation, where the rate was 0.04-0.06 min-1. This protection by tissue factor was also observed in pure systems and apparently required factor VII.
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PMID:Analysis of the generation and inhibition of activated coagulation factor X in pure systems and in human plasma. 372 68

Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.
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PMID:Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site. 396 13

Automated procedures involving a chromogenic substrate sensitive to thrombin-sarcosine-Pro-Arg p-nitroanilide were compared with conventional tests for prothrombin times and activated partial thromboplastin times (APTT) and with specific assays for factors V, VII, VIII, IX, X, XI, and XII. The reproducibility and sensitivity of the chromogenic tests were compared with those of the clotting tests. Further, we have confirmed that the chromogenic test for APTT is sensitive to factor VII deficiency, unlike the clotting test for APTT. This might be an advantage in monitoring orally anticoagulated patients. The ready availability of the automated equipment for performing the chromogenic tests suggests their potential for routine use. However, some discrepant results in certain patients with liver disease and in others with factor VIII inhibitors warrant caution.
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PMID:A clinical evaluation of automated chromogenic tests as substitutes for conventional prothrombin time and activated partial thromboplastin time tests. 399 63

A telescoped model of nephrotoxic nephritis in the rabbit, using guinea pig antiglomerular basement membrane IgG in rabbits preimmunized with guinea pig IgG, reproducibly induced crescentic nephritis. Procoagulant activity (PCA) was measured in sieve-isolated glomeruli that had been either sonicated or cultured for 48 hours. In both sonicated and cultured glomeruli PCA peaked on days 5 and 6. The time course for appearance of PCA corresponded precisely with the appearance of proteinaceous material containing fibrin in Bowman's space as measured by a light microscopic histologic scoring system and confirmed by immunofluorescence and electron microscopy. Glomerular PCA returned to baseline by days 9 and 10 in spite of progression of glomerular injury. PCA also appeared in urine. Urine PCA peaked on day 8 and persisted through day 12 when glomerular PCA had returned to baseline. Glomerular and urine PCA were characterized using human coagulation factor-deficient plasmas and antithromboplastin IgG. Both glomerular PCA and urine PCA were inhibited by antithromboplastin IgG, showing that thromboplastin (tissue factor) contributed to PCA. The PCA in glomerular sonicates was dependent on factor X, but independent of factor VII or Hageman factor, suggesting that factor VII was present. Following glomerular culture for 48 hours the PCA had changed and in some cases was dependent on Hageman factor, factor IX, and factor VII for full PCA expression. Urine PCA was uniformly Hageman factor dependent and sometimes independent of factors VII and X. No active thrombin was present. The forms of glomerular and urine PCA were, therefore, complex. They seemed to be primarily driven by thromboplastin but also appeared to require the presence of the intrinsic coagulation pathway for full expression of PCA.
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PMID:Procoagulant activity in glomeruli and urine of rabbits with nephrotoxic nephritis. 402 44

A one-stage chromogenic assay sensitive to all factors of the extrinsic system has been developed. Diluted plasma is combined with tissue thromboplastin in the presence of S-2238, a thrombin-sensitive substrate. After a lag phase, log (A405/min) is linear with time up to the maximal thrombin concentration. The linear slope, b, is called the thrombin activation rate constant (TARC). Log b, or b, is linearly related to log transformations of plasma dilutions, of factor concentrations, of dicumarolized plasmas, and of one-stage prothrombin times. Since the lag phase can vary from 2 to more than 10 minutes, it is difficult to perform the assay on current automated equipment. Results show that factors VII and X affect the lag phase, while factors V and II do not. Small amounts of sera or thrombin, to a lesser extent, can shorten the lag phase to near zero without altering the relationships between TARC and plasma dilutions and between TARC and prothrombin times for dicumarolized plasmas and for dilutions of factor-deficient plasmas. The only effects of some sera are to increase b by approximately 20 percent. Successful sera can be made from clotted whole blood or supernatants of sera from citrated plasma clotted with tissue of partial thromboplastins. These sera appear to have minimal amounts of factor X, undetectable prothrombin, and undetectable free thrombin. The sera contain excesses of factor VII and/or factor VIIa and nearly 20 percent of factor V. If the sera activity arises from the extrinsic system, it is probably due to factor VIIa.
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PMID:Effect of sera on thrombin activation rate constants: a one-stage assay for the extrinsic system. 616 32

Experiences in the application of chromogenic substrates for the evaluation of clotting variables are reported. The use of a special buffer system enables the determination of factor Xa by the thrombin substrate Chromozym TH. Prothrombin in plasma can be determined using the substrate S-2238 after activation with factor Xa or Ecarin. Factor VII is activated with thromboplastin and is estimated indirectly via factor Xa activity. Comparison of the amidolytic method for factor VII with prothrombin times of patients on oral anticoagulants shows good correlation. Chromogenic substrates can be also used for determining platelet factor 3 (S-2238), plasminogen and alpha 2-antiplasmin.
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PMID:Experience with chromogenic substrates in studies of clotting and fibrinolytic systems. 617 91

A family is described in which venous thrombosis developed in five members as early as 14 years of age. Routine coagulation studies, plasma antithrombin III, factor V, plasminogen, beta-thromboglobulin, fibrinopeptide A, prothrombin fragment F1+2, and thrombin-antithrombin III complex were all within normal limits. However, defective release of vascular plasminogen activator was observed on several occasions in all five subjects as compared with a control population of 125 persons (0.04 Committee on Thrombolytic Agents [CTA] units/ml plasma as compared with 0.21 CTS units/ml). In addition, levels of factor VII/von Willebrand's factor were significantly elevated above the normal range in this pedigree.
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PMID:Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor. 640 91


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