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)

A thrombin-independent transglutaminase (TG) has been identified in vascular cells and tissues from human, rabbit, rat, porcine, and bovine sources. The vascular TG had several properties that were similar but not identical to guinea pig liver TG. Both enzymes had similar chromatographic and electrophoretic properties, preferentially cross-linked the alpha-chains of fibrinogen, and reacted with polyclonal and monoclonal anti-guinea-pig liver TG antibodies. However, the TG from adult bovine aortic endothelial (ABAE) cells exhibited a novel Ca2+/Mg2+ dependence for enzymatic activity that was distinct from that of purified guinea pig liver TG. The mol wt of the vascular TG (79 +/- 3 kd) determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was slightly lower than the purified guinea pig liver TG (85 +/- 9 kd). The TG antigen was detected by immunohistochemical techniques in association with the endothelial and smooth muscle cells of arteries, veins, venules, and capillaries. The TG antigen also codistributed with the fibronectin antigen along the hepatic sinusoids. The ABAE cell TG cross-linked alpha 2-plasmin inhibitor to fibrinogen and caused the modified fibrinogen to be 40-fold more resistant to plasminolysis. A thrombin-independent TG in vascular cells of blood vessels could provide an alternate pathway to inhibit fibrinolysis and promote fibrin stabilization.
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PMID:The transglutaminase in vascular cells and tissues could provide an alternate pathway for fibrin stabilization. 288 23

Activated polymorphonuclear neutrophils (PMN) and macrophages generate oxidizing agents similar to or identical with N-chloroamines. Mimicking this oxidation in normal human plasma by usage of chloramine T (CT), we observed an oxidant concentration-dependent inactivating effect on plasma alpha 2-plasmin inhibitor (alpha 2-PI), antithrombin III (AT III), and alpha 1-proteinase inhibitor (alpha 1-PI). 20-50 mumol CT/ml plasma are necessary for almost complete inactivation of alpha 2-PI and AT III-activity, i.e. about 2-5 times the dose necessary for inactivation of alpha 1-PI which has already been classified as "oxidant sensitive". The inactivation of alpha 1-PI, alpha 2-PI and AT III in plasma by oxidants is the result of a specific oxidative damage since C1-inhibitor, serine proteinases and complexes of plasmin and alpha 2-PI were chloramine resistant under the conditions used. According to our results, the amount of chloramines released by 1 x 10(6) activated PMN, namely ca. 10 nmol (see Weiss et al. Science 222 625-628, 1983) would be sufficient to destroy alpha 1-PI and alpha 2-PI activity of 1.5 and 0.4 microliter of human plasma, respectively. Consequently, activated leukocytes may be able to create a microenvironment in which elastase as well as plasmin and thrombin can display their proteolytic activity unchecked by their regulator proteins. Oxidation may provide a general basis for altering enzyme/inhibitor balances.
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PMID:Inactivation of serine proteinase inhibitors (serpins) in human plasma by reactive oxidants. 326 55

There exist different ways of assays of plasminogen which give information about different properties of this proenzyme. The concentration of plasminogen can be determined by its antigenicity. Since the normal concentration of plasminogen in plasma is between 15 and 25 mg/dl the test can be carried out by simple methods such as radial immunodiffusion on Partigen plates. The possibility of errors is small and there is no need of special apparatus. The disadvantages are the lapse of 24 h until the result is available and the fact that the knowledge of the concentration does not give any information about the activity. The activity can be measured by different coagulation tests. A typical assay would involve activation of plasminogen to plasmin, addition of plasminogen-free thrombin and measuring of the lysis time. The result is however, dependent on more than one variable. Plasmin is rapidly inhibited by alpha-2-antiplasmin (APL) and there is also a dependence of the lysis time on the amount of clottable fibrinogen in the test system. Better results can be obtained by the use of diluted test plasma and addition of a constant amount of plasminogen-free fibrinogen. A different way would be the use of the euglobulin fraction instead of plasma. This has however, the possible disadvantage of incomplete precipitation of plasminogen. Instead of coagulation tests the activity can also be determined when diluted activated plasma is placed on plasminogen-free fibrin plates and the amount of lysis in the plate is recorded. All assays of this group also depend on the method of activation of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Basics and practice in evaluating plasminogen. 328 Apr 24

The thrombolytic properties of anisoylated plasminogen streptokinase activator complex (BRL 26921) and clinical results of the treatment were studied in 10 consecutive patients with acute myocardial infarction. Exclusion criteria were general contraindications against thrombolytic therapy and a time interval of more than 4 h between the onset of symptoms and admission to the hospital. All patients received a 250-mg bolus of prednisolone prior to intravenous injection of 30 mg BRL 26921 within 2 min. A continuous infusion of heparin at a dose of 1,000 USPU/h was started 2 h after the injection. Blood pressure was monitored via an arterial line. Arrhythmias and changes in the ST segments were documented by conventional ECG recording and computer-based ECG monitoring. Coronary arteriography and left ventriculography were carried out within 72 h. Besides routine laboratory tests, serial CK and CK-MB activity measurements were carried out. We determined the following hemostaseological parameters before and 15 min, 30 min, 1 h, 4 h, and 12 h after application of BRL 26921: prothrombin time, activated partial thrombosplastin time, thrombin time, thrombin coagulase time, fibrinogen, streptokinaseplasminogen activator activity, plasminogen and alpha-2-antiplasmin. Our results (reperfusion in all patients angiographically and in 7 to 8 of 10 patients from noninvasive criteria) show that BRL 26921 is a highly effective thrombolytic agent in patients with myocardial infarction, when compared with high-dose systemic fibrinolysis. Applied in dosages required for early reperfusion, it does not appear to be selectively thrombolytic and is not free of hypotensive effects in man. The decrease of fibrinolytic activity is biphasic with a half-disappearance time of 112 min.
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PMID:[Bolus injection of anisoylated plasminogen-streptokinase activator complex (BRL 26921) as an alternative concept of systemic lysis in acute myocardial infarct]. 353 4

Sixty healthy men in three physical fitness categories (sedentary, on no organized fitness program; joggers, running 5-15 miles/wk; and marathoners, running greater than 50 miles/wk) were evaluated for changes in blood clotting and fibrinolytic activity before and after maximum exercise on a treadmill according to the Bruce protocol. The rate of blood clotting, as measured by prothrombin times, partial thromboplastin times and thrombin times, was accelerated by exercise (all P less than 0.005). The ability of euglobulin clots and plasma clots to lyse incorporated 125I-fibrin, termed 125I-euglobulin clot lysis (IEL) and 125I-plasma clot lysis (IPCL), were used as indexes of fibrinolytic activity. Marathoners had greater increases in fibrinolytic activity with exercise (76% compared with 63% for joggers and 55% for sedentary subjects by IEL; 427% compared with 418% for joggers and 309% for sedentary subjects by IPCL; all P less than 0.05). Fibrin degradation products increased with exercise (P less than 0.005 for the total group of 60 subjects). The absolute concentrations of alpha 2-plasmin inhibitor, alpha 2-macroglobulin, and antithrombin III increased with exercise (all P less than 0.005), but when concentrations were corrected for acute shifts of plasma water during exercise, the quantity of these inhibitors actually decreased (all P less than 0.005). The changes in clotting assays with exercise were not significantly correlated with changes in whole blood lactate, blood pyruvate, or rectal temperatures. Fibrinolytic assays before and after exercise correlated poorly to moderately with blood lactates (IEL: r = 0.441 and r = 0.425, respectively; IPCL: r = 0.294 and r = 0.544, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of exercise and conditioning on clotting and fibrinolytic activity in men. 359 18

The control of coagulation and fibrinolytic events appears to be primarily due to four plasma proteinase inhibitors, antithrombin III, C-1-esterase inhibitor, alpha-2-antiplasmin, and alpha-2-macroglobulin. Results to date indicate that antithrombin III controls the activity of both thrombin and Factor Xa, C-1-esterase inhibitor controls kallikrein and probably activated Hageman Factor (Factor XIIa), and alpha-2-antiplasmin controls plasmin activity. The role of alpha-2-macroglobulin is not clear since it does not appear to be a primary inhibitor of any of the above enzymes. However, it is probable that it serves two functions, first as a "transfer" agent for the rapid removal of proteinases from the circulation which have been first bound by antithrombin III, C-1-esterase inhibitor, or alpha-2-antiplasmin. The second function is probably that of a back-up inhibitor when the levels of the three important controlling plasma proteins become low. The role of other plasma inhibitors such as alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, and the inter-alpha-trypsin inhibitor in coagulation and fibrinolysis would appear to be minor since these proteins either do not inactivate enzymes involved in these systems or do so at a rate too slow to be of biological significance.
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PMID:Control of coagulation and fibrinolysis by plasma proteinase inhibitors. 620 38

Urokinase-activated human plasma was analysed by acetic acid/urea/polyacrylamide-gel electrophoresis. The bands representing plasminogen, the plasmin-alpha 2-plasmin inhibitor and plasmin-alpha 2-macroglobulin complexes were identified by immunoprecipitation with specific antibodies and by comparison with purified components. Plasminogen and the plasmin-inhibitor complexes were isolated from plasma or thrombin-clotted plasma containing 125I-labelled Glu-plasminogen (residues 1-790) and urokinase. The plasma was kept at 37 degrees C for 0.5 and 10 times the lysis time of the clotted plasma, the clotted plasma until lysis. The plasmin heavy chain from the plasmin-inhibitor complexes was subsequently prepared. Only in one case could a low-grade proteolytic conversion of Glu- forms into Lys/Met/Val-forms (residues 77-790, 68-790 and 78-790 respectively) during the preparations be detected. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and N-terminal sequence analysis of the purified plasminogen and plasmin heavy chain showed the following. The plasminogen in plasma was on the Glu- form. Glu-plasmin constituted 0.74 and 0.58 of the plasmin bound to the alpha 2-plasmin inhibitor in plasma after brief and prolonged activation respectively. The rest was Lys/Met/Val-plasmin. The clotted plasma contained about equal amounts of Glu-plasminogen and Lys/Met/Val-plasminogen, and predominantly Lys/Met/Val-plasmin complexed to alpha 2-plasmin inhibitor and alpha 2-macroglobulin. The results of the analysis of the purified material substantiated the identity of radioactive protein bands in the gel after acetic acid/urea/polyacrylamide-gel electrophoresis.
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PMID:Identification of molecular forms of plasminogen and plasmin-inhibitor complexes in urokinase-activated human plasma. 620 93

The function of fibrinolysis is to dissolve fibrin clots. The agent of fibrinolysis is plasmin, a glycoprotein with gram molecular weight (GMW) of 90,000. Under natural conditions, plasminogen is converted to plasmin by tissue plasminogen activator (TPA). Activation occurs on the fibrin surface, thus confining proteolytic activity to the appropriate site. Tissue plasminogen activator, produced by monoclonal methods, has recently been made available for limited therapeutic use. Currently streptokinase and urokinase are widely used therapeutically to activate plasminogen. These agents cause plasmin to be formed which is free in the circulation as well as bound to fibrin, resulting in proteolysis of circulating plasminogen and clotting factors. Fibrinolytic therapy has proven to be more beneficial than anticoagulation alone for deep vein thrombi and for pulmonary emboli. During therapy, laboratory studies demonstrate reduced concentrations of plasminogen, fibrinogen, and of alpha-2 plasmin inhibitor, and prolongation of activated partial thromboplastin time and thrombin time. Laboratory findings must be correlated with the clinical course. Demonstration of circulating plasmin-antiplasmin complex may be a useful indicator of active fibrinolysis.
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PMID:Fibrinolysis--a review. 623 87

A clotting enzyme associated with the hemolymph coagulation system of Japanese horseshoe crab (Tachypleus tridentatus) was highly purified from the amebocyte lysate. The method for purification consisted of gel-filtration of the lysate on a pyrogen-free Sepharose CL-6B column and affinity chromatography of the endotoxin-treated clotting enzyme on a benzamidine-Sepharose 4B column. Through these procedures, about 3 mg of the purified enzyme was obtained from 70 ml of the lysate and about 390-fold purification was achieved. The purified preparation was found to give a single major band, respectively, on polyacrylamide-gel disc electrophoresis at pH 3.2 in the presence of 6 M urea and on sodium dodecyl sulfate (SDS)-gel electrophoresis in the presence and absence of 2-mercaptoethanol. It also gave a single symmetrical peak on QAE-Sephadex A-25 column chromatography. The molecular weight of the clotting enzyme was estimated to be approximately 42,000 for the unreduced sample by SDS-gel electrophoresis. For the reduced sample, it was 30,000, suggesting that the protein consists of plural polypeptide chains bridged by disulfide(s). The Tachypleus clotting enzyme was a glycoprotein, as shown by the positive periodic acid-Schiff reaction for the protein band on SDS-gel and the amino acid analysis. The purified clotting enzyme transformed Tachypleus coagulogen to coagulin gel and hydrolyzed a chromogenic peptide substrate, Tos-Ile-Glu-Gly-Arg-p-nitroanilide for Factor Xa, liberating p-nitroaniline. The enzyme was sensitive to DFP and benzamidine. It was also inhibited partially by PCMB. Antithrombin III and alpha 2-plasmin inhibitor (alpha 2-antiplasmin) were very effective inhibitors of this enzyme among ten kinds of naturally occurring proteinase inhibitors tested. The clotting enzyme had a restricted specificity towards protein substrates and activated only prothrombin among plasma zymogens including Factor IX, Factor X, fibrinogen, plasminogen and prekallikrein. The cleavage sites of bovine prothrombin for this enzyme were the same Arg-Thr and Arg-Ile linkages as those for Factor Xa, resulting in the formation of alpha-thrombin. These results indicate that the horseshoe crab clotting enzyme is a Factor Xa-like serine proteinase rather than alpha-thrombin. It seems likely that the Tachypleus clotting enzyme is a prototype of mammalian serine proteinases participating in blood coagulation.
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PMID:A clotting enzyme associated with the hemolymph coagulation system of horseshoe crab (Tachypleus tridentatus): its purification and characterization. 714 17

We had rare opportunities to examine changes in fibrin degradation products (FDP)-D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and other coagulation parameters during the clinical courses of living-related partial liver transplantation (LRPLT). In seven out of eight recipients without severe rejection and/or disseminated intravascular coagulation (DIC), FDP-DD values reached their maximum at 5 to 10 days after transplantation, then gradually decreased. On the other hand, TAT values rose to the maximum at anhepatic or reperfusion phase of liver transplantation. These data represent hypercoagulation in consequence of tissue thromboplastin activation after extensive operation. Changes in PIC, tissue-type plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) in the clinical course of case 1 suggested that fibrinolysis was suppressed by relatively elevated level of PAI-1 around the operation, but thereafter was adversely accelerated by relatively lower levels of PAI-1. In comparison with patients with DIC, TAT was much higher but PIC was significantly lower in recipients of LRPLT. These findings indicated that marked hypercoagulation and mild to moderate hyperfibrinolysis occurred in recipients of LRPLT.
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PMID:[Changes in coagulation parameters during the clinical courses of recipients of living-related partial liver transplantation]. 747 43


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