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:3.4.21.68 (tissue plasminogen activator)
11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From July 1990 to July 1993, we performed 41 percutaneous intra-arterial thrombolysis procedures for the treatment of obstructed infra-inguinal bypass grafts in 32 patients. There were 27 men and five women with a mean age of 63 +/- 17 years (range 21 to 83 years). The symptoms of occlusion were intermittent claudication in three cases, rest pain in 12 cases, severe ischemia without sensitive-motor loss in 26 cases. Bypasses were achieved using a prosthesis in 18 cases (43.9%), a saphenous vein in 10 cases (24.4%), an arterial allograft in nine cases (21.9%), and a composite prosthesis-vein graft in four cases (9.8%) (table I). The distal anastomosis of the bypass graft was located on the popliteal artery in 26 cases (63.4%) and a crural artery in 15 cases (36.6%). The mean duration of the occlusion was 4.9 +/- 3.4 days (range 1 to 15 days). The percutaneous approach was through the contralateral common femoral artery in 26 cases (63.4%), through the ipsilateral common femoral artery in seven cases (17.1%), through the left humeral artery in eight cases (19.5%). In all cases the thrombolytic agent was the recombinant tissue-type plasminogen activator (rt-PA). Each procedure began with the injection of a five milligram bolus of rt-PA into or onto the thrombus followed by infusion of rt-PA into the thrombus at a dose of 0.05 mg/kg/h. Intravenous heparin was simultaneously administered. Serum fibrinogen, prothrombin time, and partial thromboplastin time (PTT) were measured every three hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intra-arterial thrombolysis using rt-PA for the treatment of occluded infra-inguinal bypasses]. 807 60

To screen for risk of embolism, we investigated the association between the presence of left atrial (LA) thrombus by transesophageal echocardiography (TEE) and blood coagulation tests, including thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor 1 (PAI-1), plasmin-alpha 2-plasmin inhibitor complex (PIC), D-dimer, tissue plasminogen activator (tPA), free tPA, tPA.PAI-1 complex, prothrombin fragment 1+2 and fibrin degradation product E (FDP-E) in 40 patients with atrial fibrillation (Af) (13 males, 27 females, mean age 76 +/- 8 yrs). Blood coagulation tests were performed in 21 control subjects with sinus rhythm (12 males, 9 females, mean age 75 +/- 4 yrs). LA thrombi were detected in the appendage of 8 patients and in the atrium of 6 patients. Severe atherosclerotic plaque with thrombi in the thoracic aorta were detected in 6 patients without LA thrombi. FDP-E, D-dimer and PIC increased significantly in patients with LA thrombi or aortic plaque in comparison with controls with sinus rhythm. In patients with Af, 25 of them (group A) has more than 4 abnormal coagulation values out of 9 tests and 15 of them (group B) had abnormalities in less than 3 tests. LA thrombi or aortic plaque were detected in 18 patients in group A and 2 patients in group B (72% vs 13%, p < 0.01). In 4 of 6 patients with large LA thrombi, the thrombi were resolved after administration of warfarin. Before administration of warfarin, tPA, PA-1 and tPA.PA-1 complex levels were higher in the two patients whose thrombi did not resolve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Examinations to detect left atrial thrombus and blood coagulation test analyses in aged patients with atrial fibrillation]. 807 9

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.
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PMID:Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood. 808 78

Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, has been characterized as an extremely potent anticoagulant and reversible tight-binding inhibitor of human factor Xa (FXa). The ecotin gene was cloned by PCR, highly expressed in E. coli, and purified from the E. coli periplasm. The binding of ecotin to FXa was stoichiometric with an equilibrium dissociation constant Ki of 54 pM. The association rate constant was 1.35 x 10(6) M-1 s-1, and the dissociation rate constant, measured in the presence of human leukocyte elastase (HLE) to prevent reassociation of ecotin with FXa, was 6.5 x 10(-5) s-1. Ecotin prolonged clotting time ca. 10-fold at 0.3 microM and at 2 microM in activated partial thromboplastin time and prothrombin time assays, respectively. Ecotin did not effectively inhibit the human plasma proteases thrombin, tissue factor.factor VIIa, factor XIa, activated protein C, plasmin, or tissue plasminogen activator (t-PA); however, it did potently inhibit factor XIIa, plasma kallikrein, HLE, and bovine trypsin and chymotrypsin. Coincubation of ecotin and FXa at 10 microM each resulted in a (ecotin)2.(FXa)2 complex as determined by gel filtration. Dimerization of ecotin alone was measured by fluorescence titration which yielded a Kd of ca. 390 nM. FXa cleaved ecotin slowly at pH 4.0 between M84 and M85. Replacement of the P1 Met84 residue with Arg and Lys led to FXa inhibitors with Ki values of 11 and 21 pM, respectively. The P1 Arg and Lys mutants also significantly inhibited thrombin, factor XIa, activated protein C, plasmin, factor XIIa, kallikrein, and bovine trypsin and chymotrypsin but did not inhibit tissue factor.factor VIIa, t-PA, or HLE.
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PMID:Ecotin is a potent anticoagulant and reversible tight-binding inhibitor of factor Xa. 814 99

Early reocclusion and bleeding complications are still unresolved problems in thrombolytic therapy for acute myocardial infarction (AMI). In the present study, 16 patients treated with either fibrin-specific tissue-type plasminogen activator (t-PA) or nonspecific urokinase (UK) were studied to determine the effects of thrombolytic therapy on serial hemostatic states. Hemostatic states of each patient were estimated by measuring various plasma markers at one- to two-hour intervals during the first six hours of therapy, daily during the next three days, and subsequently on day 7. Two markers of plasma thrombin generation, thrombin antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F 1 + 2), showed an activated coagulant state immediately after thrombolytic therapy. The amount of thrombin generation indicated by these markers showed significant positive correlation with direct markers of fibrinolysis such as fibrin degradation products (FDP), while it did not show any correlation with the markers for plasmin generation. The potential for coagulation as indicated by prothrombin time (%) decreased with thrombolysis using fibrin nonselective agents, owing perhaps to destruction of coagulant factors by free plasmin. Fibrinolytic activity induced by thrombolytic therapy for AMI caused transient activation of the coagulant system, which could contribute to early reocclusion. Fibrin nonselective agents decreased the potential for coagulation by destroying clotting factor through the generation of free plasmin. These data provide theoretical support for simultaneous administration of anticoagulant therapy with fibrin-specific thrombolytic agents.
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PMID:Serial changes in coagulant activities after thrombolytic therapy for acute myocardial infarction. 816 Oct 5

The pathogenesis of veno-occlusive disease (VOD) of the liver appears to be secondary to endothelial damage of terminal hepatic venules, which leads to activation of the coagulation cascade, fibrin deposition, and eventual fibrous obliteration of the hepatic venules. Patients with VOD usually present with jaundice, hepatomegaly, weight gain, and ascites. This complication is usually associated with a high mortality rate. We report here the frequency and treatment of VOD in our autologous bone marrow transplant (BMT) patient population. Three of 15 (20%) children (median age 9 years) developed VOD and were treated with recombinant tissue plasminogen activator (rt-PA). Two of these three patients were prepared for BMT with busulfan (16 mg/kg) and cyclophosphamide (Cytoxan, 200 mg/kg), while the other child received cytosine arabinoside (ARA-C 18 g/m2), Cytoxan (3,600 mg/m2) and total body irradiation (TBI, 1,400 y). VOD developed between days 7-24 posttransplant. Clotting studies obtained pretransplant and during VOD included prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin-degradation product (FDP), proteins C and S, and platelet count. There was no correlation between the incidence of VOD and coagulation status. All patients had normal pretransplant clotting studies. However, protein C levels were noted to be consistently low for those patients at the time of VOD. All three patients received rt-PA at a dose of 0.25-0.5 mg/kg for 4 days. This dose produced increased levels of FDP but did not significantly prolong PT nor PTT. Two of the patients had dramatic responses and had complete resolution of VOD within 6-12 days from the start of therapy. The other patient died of fulminant hepatic failure. It seems that rt-PA is effective in VOD of the liver, which may be associated with low protein C level.
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PMID:Recombinant tissue plasminogen activator (rt-PA) for veno-occlusive liver disease in pediatric autologous bone marrow transplant patients. 819 48

Thirty healthy young women, non-smokers and of normal weight, used a combined oral contraceptive consisting of 20 micrograms ethinylestradiol and 150 micrograms desogestrel for 9 cycles. Before and during the 3rd, 6th and 9th cycles of contraceptive use, the following parameters were measured: triglycerides, total cholesterol, HDL-cholesterol, apolipoprotein A and B, prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, protein C, plasminogen, antiplasmin, tissue plasminogen activator, platelet count, platelet aggregation, beta-thromboglobulin and platelet factor 4. The ratios of total cholesterol/HDL-cholesterol and apolipoprotein A/B remained constant or showed only a slight increase. The clotting/fibrinolytic balance showed a similar trend. There was however, an inconstant but significant increase in antithrombin III and protein C. Platelet count and platelet function parameters were unmodified. Hence the contraceptive induced no substantial changes in lipid balance or blood clotting, at least during the study period.
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PMID:Evaluation of risk of thrombosis during use of low-dose ethinylestradiol-desogestrel oral contraceptive. 823 74

Cyclotheonamide A (CA), a cyclic peptide isolated from the marine sponge of the genus Theonella was shown to be a slow-binding inhibitor of several trypsin-like serine proteinases. Values of 4.6 x 10(4), 4.8 x 10(4), 9.3 x 10(3), 2.1 x 10(3) and 2.7 x 10(2) M-1 s-1 were determined for the second-order rate constants for formation of CA complexes with thrombin, trypsin, plasmin, 2-chain t-PA and factor Xa, respectively. The equilibrium constant (Ki) was measured for dissociation of CA from the CA complex with human thrombin (Ki = 1.0 nM), bovine trypsin (Ki = 0.2 nM), human plasmin (Ki = 12 nM), human factor Xa (Ki = 50 nM) and human 2-chain tissue plasminogen activator (t-PA) (Ki = 40 nM). CA produces dose dependent increases in clotting time assays. The clotting time in the thrombin time, activated partial thromboplastin time and prothrombin time assays, were doubled by 1.5, 0.9 and 48 microM CA, respectively. A model for the binding of CA to the active site of thrombin is proposed.
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PMID:Inhibition of thrombin and other trypsin-like serine proteinases by cyclotheonamide A. 832 86

Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL-6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation.
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PMID:Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery. 836 70

1. The effects of venous occlusion on the coagulation and fibrinolytic systems were investigated in six patients with type 1 (insulin-dependent) diabetes and 11 age- and sex-matched non-diabetic control subjects. The coagulation parameters (fibrinogen, prothrombin time, partial thromboplastin time with kaolin, von Willebrand factor antigen) did not differ between patients and control subjects either before or after 20 min of venous occlusion. No rise was observed in von Willebrand factor antigen after venous occlusion in either group. 2. In the diabetic patients, chronic activation of the fibrinolytic system was found at baseline, which was indicated by a shortened euglobulin lysis time (P < 0.01), increased tissue plasminogen activator activity (P < 0.05) and decreased plasminogen activator inhibitor type 1 antigen level (P < 0.05), when compared with control subjects. In both groups venous occlusion resulted in significant increments in all measurements, except plasminogen activator inhibitor type 1 antigen level. The post-occlusion values did not differ between the two groups, except the plasminogen activator inhibitor type 1 antigen level, which remained significantly lower in the diabetic patients. The mean increments in each parameter did not differ between the two groups. 3. Coagulation and fibrinolysis were assessed in response to acute insulin-induced hypoglycaemia. Von Willebrand factor antigen levels increased significantly in both groups, with no difference in maximal increments. Significant activation of the fibrinolytic system occurred in response to hypoglycaemia, demonstrated by shortened euglobulin lysis time and increased fibrin plate lysis, tissue plasminogen activator antigen level and tissue plasminogen activator activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia. 838 39


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