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)

The effect of Norplant, a subdermal contraceptive implant containing levonorgestrel, on blood coagulation factors was investigated in 47 healthy women. Coagulation parameters were also measured in 55 subjects who were taking combination type oral contraceptives (OCs) (either a pill containing 1 mg norethisterone and 50 mcg mestranol or a preparation containing 150 mcg levonorgestrel and 30 mcg ethinyl estradiol). Blood sampling was carried out at admission and after 1, 3, and 6 months of contraceptive use. Parameters measured included platelet count, prothrombin time, thrombin time, partial thromboplastin time with kaolin, clotting factors I, II, V, and VI-XIII, plasminogen, antithrombin III, alpha 1 antitrypsin, alpha 2 macroglobulin, and fibrinogen degradation products. Norplant users showed a lack of effect on the factors tested, except for factor VII activity, which was increased, and antithrombin III concentration, which was decreased after 3 months of use. In contrast, the combined OC users evidenced marked changes in platelet count, the screening tests, and most coagulation promoting factors. These changes became more pronounced after 6 months. Women taking the levonorgestrel-ethinyl estradiol OC evidenced less pronounced changes in some coagulation parameters than those taking the norethisterone-mestranol preparation; however, the high dropout rate among OC users limits the conclusions that can be drawn from these results. These results point to a relative lack of effect of Norplant implants on the blood coagulation-fibrinolytic system, presumably due to the absence of estrogen and the low dose of progestogen delivered to the body.
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PMID:Effect of levonorgestrel contraceptive implants, Norplant, on blood coagulation. 644 Jul 38

HeLa cells have undetectable tissue factor (thromboplastin) activity when measured by a one-stage coagulation assay. In contrast, these cells accelerated the factor VII-catalyzed cleavage of factor X. The two assays gave similar results after either heating the samples to 100 degrees C for 2 min or exposure to thrombin. Neither of these treatments altered the tissue factor activity of human foreskin fibroblasts, a cell type with high tissue factor activity. HeLa cells contain an inhibitor(s) directed against factor Xa but not thrombin. The inhibitor(s) was inactivated by exposure to thrombin or by heat treatment. Inhibition of factor Xa-catalyzed cleavage of a synthetic peptide was blocked by ethyleneglycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) so the inhibition was apparently dependent on divalent cations. Inhibition was not accelerated by heparin. The inhibitor(s) was not protein C or other serine proteases since it was not inactivated by diisopropylfluorophosphate. The factor Xa inhibitor(s) has been isolated from HeLa cells with an approximate 500-fold increase in specific activity. After SDS-polyacrylamide gel electrophoresis factor Xa-inhibitory activity was recovered from a region corresponding to the major Coomassie-staining band at 43 kDa and in lesser amounts from regions corresponding to 26 and 17 kDa. Cellular inhibitors of coagulation may partially explain the low apparent tissue factor observed in some in vitro cells and may serve a regulatory role in limiting the expression of tissue factor.
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PMID:Alterations in the apparent tissue factor (thromboplastin) expression in HeLa cells by a cellular factor Xa inhibitor. 663 60

This paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I-labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through "the extrinsic pathway" with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to "make available" a platelet-derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.
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PMID:Interaction of human tumor cells with human platelets and the coagulation system. 664 93

Recent studies on the mechanism of initiation and regulation of blood coagulation are reviewed. In the intrinsic blood coagulation pathway, factor XII, prekallikrein (or factor XI) and high molecular weight kininogen from a complex on an anionic surface, such as exposed subendothelium at the site of vascular trauma. In complex, zymogen factor XII activates prekallikrein (or factor XI) by limited proteolysis to initiate the coagulation cascade. A similar initiating mechanism may be operative in the extrinsic pathway, where zymogen factor VII, complexed with a lipoprotein (tissue factor) and calcium ions, converts factor X to factor Xa. Factor Xa converts prothrombin to thrombin which converts soluble fibrinogen to an insoluble fibrin network which physically arrests the flow of blood from the damaged vasculature. In addition, thrombin converts protein C to activated protein C. Activated protein C functions as a negative regulator in the coagulation process by degrading factor VIIIa and factor Va.
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PMID:Enzymological aspects of blood coagulation. 668 3

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
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PMID:The multiple coagulopathies of biliary atresia. 669 16

The activation and inactivation of human factor VIII by thrombin have been investigated by the use of thrombin inhibitors. The addition of inhibitors to nonactivated factor VIII blocks activation by thrombin. In contrast, their addition to factor VIII activated with thrombin does not block inactivation, but causes an initial period of decay that is more rapid than in the absence of inhibitor. This effect was seen only with protease inhibitors that inhibit thrombin. After the initial decay, low levels of factor VIII coagulant activity persist in the presence of inhibitors, but an assay specific for activated factor VIII showed this to be largely a result of the persistence of nonactivated factor VIII. Only in the case of reversible inhibition is activated factor VIII present in this plateau phase. Possible mechanisms that would account for these observations were studied by iterative computer simulation of model reactions. Two classes were considered: (formula: see text). The experimental results are inconsistent with the first mechanism, which predicts that thrombin indicators should stabilize activated factor VIII (VIIIt). Alternative mechanisms were studied where activation is thrombin-dependent, but inactivation is a first-order reaction (mechanism 2). This family of mechanisms includes those where VIIIt is an VIII. thrombin complex. Simulation of the addition of thrombin inhibitors to such model systems shows the initial rapid decay of activity characteristic of the experimental observations and predicts qualitatively the different effects of reversible and irreversible inhibitors that are observed in the plateau phase. These results argue strongly against a two-cleavage model for the activation and inactivation of factor VII by thrombin and support a one-cleavage model in which inactivation is due to first-order decay. In addition, they provide a plausible mechanistic explanation for the fact that serine protease inhibitors appear to inhibit thrombin-activated factor VIII.
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PMID:The activation and inactivation of human factor VIII by thrombin: effect of inhibitors of thrombin. 677 77

Of four Holstein-Friesian calves infected with 200,000 sporocysts of Sarcocystis bovicanis, three become ill and died on days 35, 55, and 59 of a 63-day experiment. No control calves became ill or died. Serum biochemicals and hematologic indicators of hemostasis from both groups were measured throughout the experiment. Creatine phosphokinase values for both groups increased markedly during acute infection. Lactic dehydrogenase and aspartate aminotransferase values were high in infected calves on days 25 to 35 and days 24 to 63, respectively, indicating injury of muscle, liver, or other tissues. Sorbitol dehydrogenase values were significantly higher for infected than for control calves on days 25 and 35, indicating liver injury. Serum bilirubin and blood urea nitrogen values were significantly increased in three anemic infected calves from day 25 or 26 to day 35, probably reflecting destruction of erythrocytes. The fourth infected calf was not anemic and had no hyperbilirubinemia and only minimal azotemia. Serum protein and albumin values decreased in infected calves on days 21 to 30 or 35, when, although hypoalbuminemia persisted, total protein concentration increased. Glucose, calcium, sodium, and chloride values decreased in infected calves slightly before onset of illness and remained low throughout the experiment. Potassium, magnesium, and phosphorus values did not differ between infected and control calves. Activated partial thromboplastin time and Russell's viper venom time were normal; prothrombin time was significantly higher from day 27 to day 49 in infected calves. This pattern was interpreted as evidence for acquired factor VII deficiency. Abnormal retraction of blood clots and enlarged platelets in blood smears, which indicate platelet dysfunction and increased platelet turnover, respectively, were seen on days 27 through 35 in anemic infected calves. Values for thrombin time (three calves) and fibrin degradation product concentration (one calf) increased just before death of the infected calves.
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PMID:Hematology of experimental acute Sarcocystis bovicanis infection in calves. II. Serum biochemistry and hemostasis studies. 678 37

Plasma was prepared by rapid centrifugation of native blood followed by adsorption of vitamin K-dependent clotting factors with BaSO4. Compared to fresh citrated plasma, BaSO4-treated plasma contained about 80% of factor V and factor VII and the same concentration of fibrinopeptide A. Assays were also carried out after overnight incubation of citrated plasma and BaSO4-adsorbed plasma with and without added citrate and compared to assays of fresh citrated plasma. Factor V decreased to about 25% in both citrated samples, factor VIII decreased to 45% in both samples of BaSO4-treated plasma, and fibrinopeptide A did not change. Thus loss of factor V activity depended on reduction in divalent cation concentration whereas loss of factor VIII activity may have resulted from effects of early traces of thrombin.
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PMID:Non-decalcified barium sulfate-adsorbed plasma. A potentially useful reagent for studying blood clotting, platelets or complement. 680 95

If beta/gamma-thrombin interacted with blood plasma in vitro, shortening of recalcification period as well as partial thromboplastin time were observed in blood plasma, which were not related to low amount of alpha-thrombin in the preparation. Intensity of the procoagulant effect depended on the enzyme concentration. Presence of an excess of phospholipids did not inhibit this effect suggesting that the latter did not involve the thrombocytic factor 3 liberation. Factor V was shown to be activated by beta/gamma-thrombin in blood plasma, the rate of which depends on the enzyme concentration; the activation was not due to low content of alpha-thrombin in the preparation. Activation of factor V was only responsible for the procoagulant activity of beta/gamma-thrombin as shown by time-analysis of the reaction and by the enzyme concentrations used. Interaction of beta-gamma-thrombin with blood plasma led also to a gradual decrease in activity of factor VIII and did not affect the factor VII activity. The data obtained showed that beta/gamma-thrombin, deprived of ability to coagulate fibrinogen, maintained its activity towards the other factors of blood coagulation, suggesting the presence of independent haemostatic function in the enzyme.
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PMID:[Procoagulant properties of beta/gamma-thrombin]. 681 May 43

Spectrophotometric assays for the measurement of coagulation factor activities in plasma have been developed using a relatively specific chromogenic substrate for thrombin. The tissue-factor-activated assay system involves the activation of factors VII and X and prothrombin. The surface-activated assay system involves the activation of factors XII, PK, XI, IX, VII, X and prothrombin using factors V and VIII as cofactors. The thrombin generated subsequent to activation in these two assay systems is measured via its activity on the chromogenic substrate Sarc-Pro-Arg-pNA. These spectrophotometric assays provide a higher degree of sensitivity as compared with the clotting time assays. The tissue-factor-activated system provides a sensitive method for monitoring coumarin therapy. The surface-activated assay system can detect deficiencies of all the factors measured by the conventional APTT assay system, as well as factor VII. Furthermore, this assay provides a sensitive method for monitoring heparin therapy.
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PMID:Chromogenic substrate spectrophotometric assays for the measurement of clotting function. 694 78


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