Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An analysis of haemostatic variables was done in 31 prostate cancer patients treated with oestrogens (13 pts), estramustine phosphate (7 pts) or orchidectomy (11 pts) before, at about 7 weeks and 6 months of treatment. Six patients treated with either of the drugs developed venous thromboembolism or ischemic vascular disease. Already before treatment there were changes indicating some activation of blood coagulation, fibrinolysis and kallikrein systems. The drug treated group showed significant changes in several variables: i.e. increase in factor VII, plasminogen and prekallikrein but also a decrease in antithrombin and in inhibitors to the fibrinolytic and kallikrein system. Significant difference between the drug treated groups was found in circulating platelet aggregates and in kallikrein inhibiting activity. Tissue plasminogen activator capacity was significantly lower in the drug treated patients with complications than in those without. The study also showed that in addition to the assay of the tissue plasminogen activator capacity during the first weeks of therapy it might be helpful in predicting cardiovascular complications to investigate platelet aggregates, prothrombin complex, factor X, von Willebrand factor antigen, fibrinogen, antithrombin, fibrino-peptide A, and the inhibitors of fibrinolysis as well as C1-esterase inhibitor.
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PMID:Changes in blood coagulation and fibrinolysis in patients on different treatment regimens for prostatic cancer. Predictors for cardiovascular complications? 312 58

Alteplase is a human tissue plasminogen activator (t-PA) produced by recombinant DNA technology. It is a relatively fibrin-specific thrombolytic agent, used primarily to lyse coronary artery clots. It has proven effective in the treatment of acute myocardial infarction (AMI). Despite continuous reevaluation of pharmacokinetic parameters for t-PA, limited distribution and clearance data mandate administration of t-PA as a continuous infusion. Tissue plasminogen activator is eliminated primarily by hepatic metabolism with an elimination half-life of five to ten minutes. Plasma levels show great interindividual variation but correlate with infusion rate and decrease in fibrinogen level. The current recommended dose is 100 mg administered as a 10-mg iv bolus followed by a continuous infusion over three hours. However, 40-150 mg has been used in clinical trials. The compound has undergone extensive testing, comparing it with placebo and streptokinase (SK), and combining it with angioplasty and coronary artery bypass surgery. Tissue plasminogen activator is effective at opening clotted coronary arteries in approximately 70 percent of AMI patients and has been shown to be approximately twice as effective as SK in one U.S. trial. Although there is considerable evidence of efficacy with t-PA, data evaluating the influence of t-PA on mortality are limited, but suggest a reduction to five percent. Currently, thrombolytic therapy is indicated for patients experiencing a transmural AMI with onset of symptoms within three to six hours before presenting to the emergency room. Active internal bleeding or conditions predisposing to serious hemorrhage are contraindications to thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteplase: a tissue plasminogen activator for acute myocardial infarction. 312 86

To assess the thrombolytic efficacy and the effect on the systemic fibrinolytic system of recombinant tissue plasminogen activator doses of 20 mg, 50 mg, and 100 mg were compared in a randomised study. Tissue plasminogen activator was infused intravenously over 90 minutes in 50 consecutive patients with acute myocardial infarction of four hours' duration or less; on average the infusion was started 135 minutes (range 20 to 240) after the onset of pain. The affected artery was patent at the end of the 90 minute infusion in 14/17 (82%) of those who received 100 mg, 12/17 (71%) of those who received 50 mg, and 8/16 (50%) of those who received 20 mg. Regardless of dose, reperfusion rates were significantly better for patients treated within two hours of the onset of symptoms (81%) than for those treated in the third and fourth hours (54%). At the end of the infusion serum fibrinogen concentrations fell to 86% of the preinfusion value after 20 mg, 75% after 50 mg, and 63% after 100 mg, and similar dose dependent changes occurred in plasminogen, (alpha 2 anti-plasmin, and fibrinogen and fibrin degradation products. The mean infarct related regional third ejection fraction was 46% for patients with grade 2 or 3 reperfusion and 35% for those with grade 0 or 1. Ventricular fibrillation occurred in six (12%) patients during the infusion of tissue plasminogen activator, but no late ventricular fibrillation occurred. Bleeding was minimal, reocclusion occurred in three patients, and four patients died from cardiac causes. Recombinant tissue plasminogen activator is an effective thrombolytic agent which produces better reperfusion rates after a 50 or 100 mg dose than after a 20 mg dose. The effect on the systemic fibrinolytic system is dose dependent. Successful reperfusion results in improvement of left ventricular function.
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PMID:A randomised dose ranging study of recombinant tissue plasminogen activator in acute myocardial infarction. 313 31

Tissue plasminogen activator's thrombolytic action is relatively specific for fibrin; however, systemic bleeding can occur in patients, especially when heparin is simultaneously administered. We describe two cases of intracerebral hemorrhage from a cohort of 450 patients (0.44%) treated at one institution with tissue plasminogen activator and heparin for acute myocardial infarction. A pooled worldwide review of 5258 cases from several clinical protocols for treatment of acute myocardial infarction, using tissue plasminogen activator from one source, revealed a similar overall incidence of 0.68%. The incidence of intracerebral hemorrhage may be reduced by lowering the total dose of tissue plasminogen activator or by reducing the infusion rate and duration. The incidence of central nervous system hemorrhage with tissue plasminogen activator is within the range reported with streptokinase, but because equal coronary artery thrombolytic doses are not known, no definitive comparison is possible.
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PMID:Intracerebral hemorrhage complicating intravenous tissue plasminogen activator treatment. 314 Jul 69

Various human malignant tumors, including malignant melanoma, showed an absence of fibrinolytic activity by the histochemical fibrin slide method. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture, and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsied specimens of melanoma and several melanoma cell lines by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues and cell lines while the various inhibitors of fibrinolysis, including alpha 2-anti-plasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, and antithrombin III were found intracellularly only in the melanoma tumor cells, but not in melanoma cell lines. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. This hypothesis is supported by in vivo studies showing binding of tissue plasminogen activator in cultured cell lines to several inhibitors. Since these are potent inhibitors of fibrinolysis, their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.
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PMID:Tumor growth and metastases in malignant disease. A review. 314 46

By using an enzyme-linked immunosorbent assay, we detected a significant amount of tissue plasminogen activator (0.8 +/- 0.17 ng/ml) in the aqueous humor of ten normal human eyes. It was also identified on Western blot analysis. The ratio of tissue plasminogen activator to total protein in aqueous humor was about 30 times greater than the ratio of tissue plasminogen activator to total protein in plasma. There was evidence that at least some of the tissue plasminogen activator in the aqueous humor was synthesized locally by the structures bordering the anterior chamber of the eye. Tissue plasminogen activator may be a useful therapeutic modality in clinical conditions of delayed dissolution of fibrin in the eye.
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PMID:Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance. 314 67

Various human malignant tumors including malignant melanoma showed an absence of fibrinolytic activity in previous histochemical fibrin studies. In contrast, a tissue plasminogen activator has been isolated both from extracts of melanoma tissues and melanoma cell lines in culture and has been characterized to be a potent plasminogen activator. In an attempt to resolve this apparent discrepancy, we studied biopsies specimens of melanoma, several melanoma cell lines and melanoma xenografts by the immunoperoxidase method. Tissue plasminogen activator was observed in melanoma tissues, cell lines and xenografts, while various inhibitors of fibrinolysis, including alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin and antithrombin III, were found intracellularly only in the melanoma tumor cells but not in melanoma cell lines nor in xenografts. We believe that these inhibitors are derived from the blood and are bound to the tissue plasminogen activator within the melanoma cells. Their presence in tumor cells would explain the lack of fibrinolytic activity in melanoma tissues.
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PMID:Tissue plasminogen activator and inhibitors of fibrinolysis in malignant melanoma. 314 30

In this study, the importance of anthropometric, nutritional and endocrine variables on the plasma concentrations of tissue plasminogen activator antigen (tPA) and plasminogen activator inhibitor (PAI-l) were investigated. Tissue plasminogen activator concentration and PAI-l activity in plasma were studied in 24 healthy young women after diet periods which caused depletion or filling of hepatic glycogen stores. Plasminogen activator inhibitor levels in the glycogen-depleted state and the glycogen-repleted state were positively correlated, as were also tPA levels. In fasting subjects with repleted glycogen stores, tPA values correlated with fasting insulin concentration and blood pressures. In fasting subjects depleted of glycogen stores, PAI-l correlated with tPA, plasma insulin, triglycerides, and waist-to-hip girth ratio; triglycerides and waist-to-hip girth ratio also correlated with tPA. Over a 4-h period following intake of a test-meal, the glucose and insulin responses were not correlated with the fibrinolytic variables. Multivariate regression analysis suggested that waist-to-hip girth ratio and diastolic blood pressure were independently associated with tPA concentrations both in subjects with depleted and repleted glycogen stores. Thus, both constitutional factors such as anthropometric variables and blood pressure, and nutritional status of the subjects may be related to tPA and PAI- levels in plasma. This should be taken into account in clinical studies on fibrinolysis.
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PMID:The effect of body build, diet and endocrine factors on the extrinsic fibrinolytic system in healthy young women. 314 34

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.
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PMID:Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty. 316 Jul 57

Immunoreactive plasminogen activators were studied in tissue sections using a peroxidase method and monospecific antibodies to tissue plasminogen activator produced by a melanoma. Tissue plasminogen activator reactivity was found in skin melanomas and in endothelial and smooth muscle cells of arteries and veins. Vessels of the umbilical cord showed higher reactivity than peripheral vessels. Only faint antiurokinase reactivity was found. By means of the fibrin slide technique, fibrinolytic activity could be shown in peripheral vessel walls but not in the umbilical cord, which suggests that immunoreactivity of tissue plasminogen activator bound to an inhibitor can also be demonstrated. This method may be a useful tool in further studies of tissue plasminogen activator in physiological as well as pathological processes.
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PMID:Immunohistochemical localisation of tissue plasminogen activator and urokinase in the vessel wall. 388 80


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