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)

In 10 patients with nephrotic syndrome (NS), the coagulation inhibitors, the fibrinolytic system and several functions of the fibrinogen-fibrin molecule were studied. Among the coagulation inhibitors, only antithrombin III (AT III) was found decreased and correlated with serum-albumin levels. Venous occlusion test provoked a normal tissue plasminogen activator (tPA) release in all patients. The plasminogen activator inhibitor (PAI) had an increased activity in 5 out of the 10 patients. Thrombin and reptilase times were found abnormal in most patients. The thrombin time (TT) prolongation correlated with serum albumin levels and was corrected by adding purified albumin. The fibrinogen was purified from each of the 10 patients' plasma. Only 2 of them showed abnormal polymerization in purified system, suggesting dysfibrinogenaemia. Other functions (thrombin binding, tPA stimulating activity, lysis by purified plasmin) were found normal except in one of the 2 patients with dysfibrinogenaemia whose fibrinogen lysis by plasmin was delayed. It is concluded that an abnormal fibrinogen molecule is not the most frequent explanation for thrombin time prolongation in NS.
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PMID:A study of fibrinogen and fibrinolysis in 10 adults with nephrotic syndrome. 314 81

Tissue plasminogen activator (t-PA) purified from culture of human lung cells was infused over 30 min at the dose of 7.2 mg or 14.4 mg per person into human male volunteers. T-PA declined rapidly after the cessation of infusion with T1/2, alpha of about 4 min and T1/2, beta of about 40 min. The plasma fibrinogen and plasminogen did not change during and after the infusion of t-PA. The concentration of alpha 2antiplasmin (alpha 2AP) did not change but that of alpha 2AP-plasmin complex increased to about 200 nM at the infusion of 14.4 mg/person. Fragment D was hardly found at the infusion of 7.2 mg but some increase in the concentration of D was observed at the infusion of 14.4 mg. The concentration of free plasminogen activator inhibitor (PAI-1) rapidly declined and kept low up to 150 min, and returned to normal the following day. The concentration of t-PA-PAI-1 complex increased rapidly, and slowly declined after the end of the infusion of t-PA, suggesting no significant release of PAI-1 in response to increase in plasma concentration of t-PA or t-PA-PAI-1 complex. The addition of thrombin to the blood after withdrawal resulted in the significant formation of D-dimer, even at 150 min after the infusion. There was not hyperaggregability of platelets during and after the infusion of t-PA. These results suggest that the infusion of t-PA at the dose of 7.2 mg or 14.4 mg/person for 30 min resulted in high fibrinolytic potential in the blood without the breakdown of fibrinogen or increase in PAI-1.
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PMID:Changes in various parameters of fibrinolysis in persons infused with tissue plasminogen activator: special reference to plasminogen activator inhibitor. 314 66

The regulation of the fibrinolytic system is of critical importance during hemostasis, wound repair, neoplasia, inflammation, and a variety of other biologic processes. This control is achieved in a large part through the action of specific plasminogen activator inhibitors (PAIs). Cultured endothelial cells (ECs) produce type 1 PAI (PAI-1), the physiologic inhibitor of tissue-type plasminogen activator. PAI-1 is one of the most highly regulated of the fibrinolytic components produced by ECs. Its synthesis is modulated by a variety of compounds including endotoxin, thrombin, transforming growth factor beta interleukin 1, and tumor necrosis factor alpha. Recent studies suggest that PAI-1 is synthesized by ECs as an active molecule, but that it spontaneously decays into a latent form in solution. Specific components present in the extracellular matrix of ECs and in plasma bind to PAI-1 and prevent this inactivation. The unexpected finding that cultured ECs also produce type 2 PAI (PAI-2) introduces a previously unsuspected level of complexity to our understanding of this system and raises the possibility that the altered fibrinolytic activity of ECs following various treatments, or of blood in certain individuals, may reflect changes in either one of these inhibitors.
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PMID:Fibrinolytic system of vascular endothelial cells. Role of plasminogen activator inhibitors. 314 26

Serum-free culture medium collected from primary monolayer cultures of human articular chondrocytes was found to inhibit human urokinase [EC 3.4.21.31] activity. Although chondrocyte culture medium contained a small amount of endothelial-type plasminogen activator inhibitor which could be demonstrated by reverse fibrin autography, most of the urokinase inhibitory activity of chondrocyte culture medium was shown to be due to a different molecule from endothelial-type inhibitor, since it did not react with a specific antibody to this type of inhibitor. The dominant urokinase inhibitor in chondrocyte culture medium was partially purified by concanavalin A-Sepharose affinity chromatography. The partially purified inhibitor inhibited high-Mr urokinase more effectively than low-Mr urokinase, but no obvious inhibition was detected against tissue-type plasminogen activator, plasmin, trypsin, and thrombin. The inhibitor had an apparent Mr of 43,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis, and it was unstable to sodium dodecyl sulfate, acid, and heat treatments. Inhibition of urokinase by the inhibitor was accompanied with the formation of a sodium dodecyl sulfate-stable high-Mr complex between them. Inhibition and complex formation required the active site of urokinase. The partially purified inhibitor was thought to be immunologically different from the known classes of plasminogen activator inhibitors, including endothelial-type inhibitor, macrophage/monocyte inhibitor, and protease nexin, since it did not react with specific antibodies to these inhibitors.
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PMID:Detection and partial characterization of a specific plasminogen activator inhibitor in human chondrocyte cultures. 314 40

A plasminogen activator inhibitor was purified to apparent homogeneity from conditioned media of U138 cells. The inhibitor is a glycoprotein with a pI of 5.4 and an apparent molecular weight of 45,000. The inhibitor forms sodium dodecyl sulfate-stable complexes with plasminogen activators and trypsin but not with plasmin, thrombin, or pancreatic kallikrein. Some biochemical and immunochemical characteristics of the U138 inhibitor distinguish it from other known plasminogen activator inhibitors. The expression of this inhibitor by U138 cells could be modulated by incubation in phorbol myristate acetate, interleukin-1, tumor necrosis factor, and gamma interferon, but not in beta interferon. Thus, the expression of the plasminogen activator inhibitor can be influenced by biological response modifiers known to be active in the brain and in the neural response to inflammatory stimuli. Therefore, this inhibitor, along with protease nexin, may be involved in brain development and regulation.
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PMID:Purification and partial characterization of a plasminogen activator inhibitor from the human glioblastoma, U138. 314 98

The effects of human activated protein C (APC) and thrombin on plasminogen activator inhibitor (PAI-1) released from cultured human umbilical endothelial cells, grown in serum-free 35S-methionine containing medium, were studied in two ways: measurement of PAI-1 activity with an amidolytic assay, and immunoprecipitation of the medium with anti-PAI-1 IgG, anti-protein C IgG or anti-thrombin IgG followed by SDS-PAGE and autoradiography. Addition of APC or thrombin to the endothelial cell conditioned medium results in a time and concentration dependent loss of PAI-1 activity and in the degradation of PAI-1 from 46 kD into a 42 kD product. After incubation of the medium with APC in the presence of cells, an additional band of 95 kD was found, which could be immunoprecipitated with both anti-PAI-1 IgG and anti-protein C IgG, indicating the formation of an APC-PAI-1 complex before degradation occurs. No complex could be detected after incubation of the medium with thrombin in the presence of endothelial cells. Blocking the active sites of APC and thrombin prevented both the formation of APC-PAI-1 complexes and the inactivation and degradation of PAI-1. After removal of the active PAI-1 from the medium, no degradation of the inactive PAI-1 by APC or thrombin could be found. It is concluded that both APC and thrombin react with the active PAI-1, resulting in inactivation and degradation of PAI-1.
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PMID:The interaction of activated protein C and thrombin with the plasminogen activator inhibitor released from human endothelial cells. 349 80

A titration assay for the determination of the fast acting plasminogen activator inhibitor capacity (PAI-cap) was developed. Most of the hitherto published assays for fast acting PAI are reported to have the disadvantage of non-parallel titration curves of tissue plasminogen activator (t-PA) in buffer and plasma. In the assay reported here, this problem has been overcome by adequate predilution of the samples, thus achieving parallel titration curves regardless of the individual PAI-cap of a sample. Provided that values are calculated from parallel titration curves, reproducible PAI-cap values at different dilutions of a sample are obtained. This assay can be applied for the determination of PAI-cap in plasma, serum and other biological fluids as platelet releasates and endothelial cell conditioned medium. PAI-cap of plasma of 10 healthy male volunteers ranged from 15.3 to 32.3 arbitrary inhibitor units AU/ml (24.5 +/- 5.2, mean +/- SD). The alternative use of three different anticoagulants (citrate, EDTA, heparin) had no influence on PAI-cap determinations. Serum generated from blood contained a mean of PAI-cap of 129% in comparison to the plasma of the same donor indicating the release of PAI from cells during clotting. Plasma PAI-cap changed during the day with a constant decrease from the highest levels in the morning (100%) to low levels in the evening (62.9%). Platelets aggregated by thrombin released plasminogen activator inhibitor amounting to a mean PAI-cap of 4.33 +/- 2.98 AU per 2.5 X 10(8) cells.
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PMID:Method for the determination of fast acting plasminogen activator inhibitor capacity (PAI-cap) in plasma, platelets and endothelial cells. 379 11

A functional, immunoradiometric assay for a specific plasminogen activator inhibitor (PAI) was developed. This assay was based on the ability of the PAI to bind rapidly and strongly to immobilized tissue-type plasminogen activator (tPA). The extent of binding was quantified by incubating the PAI-tPA complex first with rabbit antiserum to the PAI and then with 125I-labeled goat anti-rabbit IgG. The interaction between tPA and the PAI was rapid, time- and concentration-dependent, sensitive over a broad range of PAI concentrations (1 to 100 ng/ml), and competed by urokinase but not streptokinase. The widespread application of this new technique was indicated by its ability to detect an immunologically related PAI not only in a number of other cell types, but also in platelets from which it can be released by thrombin, and in blood. This assay thus provides a quantitative approach for assessing the role of this PAI in a variety of fibrinolytic processes.
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PMID:Immunoradiometric assay to measure the binding of a specific inhibitor to tissue-type plasminogen activator. 393 Jun 37

The aim of the present study was to determine whether patients with previous cerebrovascular disease have abnormalities in hemostatic functions stimulated by a 5-min venous-occlusion-test. Twenty-two patients with brain ischaemia 3-6 months previously were compared to a control group of twenty patients with non-vascular neurological diseases. Cases showed less increase in tissue plasminogen activator and fibrin degradation products than controls. There were no differences in baseline and stimulated levels of plasminogen activator inhibitor, fibrinogen degradation products, thrombin-antithrombin complex or global lysis assay (Fibriscreen). Since patients with acute cerebrovascular disease were not included, the present findings may represent either preexisting or longterm reactive fibrinolytic deficiencies, possibly predisposing to further thrombotic disease.
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PMID:Decreased fibrinolytic stimulation by a short-term venous occlusion test in patients with cerebrovascular disease. 748 39

This investigation presents data which indicate that the plasminogen activator inhibitor (PAI) activity secreted from U138 cells is composed of three separate PAIs: PAI-1, PAI-2, and PN-1. It was demonstrated that the U138 PAI-1-like protein had an apparent molecular mass of 50 kilodaltons (kDa) and was purified to apparent homogeneity by elution from an anti-PAI-1 immunoaffinity column. These fractions were also reactive with a second anti-PAI-1 monoclonal antibody using immunoblotting techniques. Northern blot analysis of RNA isolated from unstimulated U138 cells demonstrated positive hybridization with the cDNA specific for human PAI-1. The U138 PAI-2-like protein was adherent to an anti-PAI-2 immunoaffinity column and was demonstrated to be nonadherent to concanavalin A-agarose, heparin-Sepharose, and the anti-PAI-1 immunoaffinity column. The eluted U138 PAI-2-like protein was demonstrated to have an apparent molecular mass of 60 kDa and was also reactive with a second anti-PAI-2 monoclonal antibody using immunoblotting techniques. Further, the cDNA specific for PAI-2 was demonstrated to hybridize to a 2.5-kilobase message from RNA isolated from U138 cells. A third PAI was detected that was nonadherent to concanavalin A-agarose and both of the anti-PAI columns. This 50-kDa PAI was adherent to heparin-Sepharose and thrombin-agarose columns, and was not reactive with any antibodies for either PAI-1 or PAI-2. Northern blot analysis of U138 RNA demonstrated positive hybridization with an oligodeoxynucleotide specific for PN-1. This investigation demonstrates with biochemical, immunological, and molecular data that the U138 glioblastoma constitutively produces three PAIs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purification and characterization of the plasminogen activator inhibitors PAI-1, PAI-2, and PN-1 from the human glioblastoma U138. 750 41


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