Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase (UK), a fibrinolytic enzyme activator purified from human material was immobilized on nylon using different procedures. One was a modified method of immobilization of antigen or antibody initially carried out by Edelman and others in 1971 (Procedure I). The other was our newly devised method (Procedure II) (Sugitachi et al. 1976). Major specificities of the immobilized UK are as follows: 1. The UK revealed properties of a plasminogen activator and the optimum pH of the immobilized UK was between 7.2 and 7.4, these values being in good parallel with that of soluble UK. The immobilized UK maintained a stable fibrinolytic activity after long-term preservation and heat-treatment. 2. As the fibrinolytic activity of immobilized UK was found to be inhibited by the antiplasmin in human plasma, an antiplasmin inhibitor was immobilized on the nylon together with the UK. The antiplasmin activity was to some extent prevented using this procedure. 3. Nylon tubes immobilized with UK and antiplasmin inhibitor were used for thrombotic coagulation studies carried out according to the method of Chandler. Thrombus formation time (TFT) of UK-immobilized tubes was 30 min, while that of the non-treated tubes was no longer than 10 min.
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PMID:Immobilization of plasminogen activator, urokinase, on nylon. 58 Sep 91

Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.
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PMID:Advances in thrombolytic therapy. 139 Mar 21

Thrombus formation in anesthetized, open-chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery. One-hour postocclusion, administration of vehicle to heparinized dogs (n = 12) did not induce reperfusion despite concomitant treatment with acetylsalicylic acid (ASA), sulotroban, or saline. Intravenous bolus injection of 140 kU/kg (= 0.24 mg/kg) of the unglycosylated t-PA variant BM 06.022 induced reperfusion in 4 out of 6 dogs, followed by flow deterioration. Pretreatment with i.v. ASA did not improve coronary blood flow (CBF). Conjunctive treatment with the thromboxane A2-receptor antagonist, sulotroban, (10 mg/kg i.v. bolus, followed by 10 mg/kg/h) or with recombinant hirudin, a specific thrombin inhibitor, (1 mg/kg/h) 30 min prior to i.v. injection of BM 06.022, prolonged (p < 0.01) the cumulative patency time (sum of time-intervals in which the coronary artery was patent) to 147.4 +/- 9.2 min in 4 out of 6 reperfused dogs and 129.9 +/- 12.3 min in 7 out of 8 dogs, respectively, compared to the saline plus BM 06.022 treatment (47.5 +/- 13.1 min) in 4 out of 6 dogs. The terminal CBF was higher (p < 0.01) after sulotroban plus BM 06.022 (7.0 +/- 1.7 ml/min) and hirudin plus BM 06.022 (6.3 +/- 1.5 ml/min) than after saline plus BM 06.022 (0.8 ml/min). These findings demonstrate that drugs with antithromboxane or antithrombin activity may improve CBF after reperfusion.
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PMID:Hirudin and sulotroban improve coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary artery thrombosis. 142 Nov 76

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.
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PMID:Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin. 143 39

To determine whether the response to thrombolytic therapy for lower-extremity deep venous thrombosis (DVT) can be predicted from the venographic appearance, 139 thrombosed venous segments were analyzed. Initial and follow-up venograms were obtained in 62 patients randomized to 24-hour infusions of recombinant human-tissue-type plasminogen activator (rTPA) (n = 34), rTPA plus heparin (n = 16), or heparin alone (n = 12). Segmental response to therapy was evaluated by means of blinded review of the paired venograms. The response (50%-100% lysis) to rTPA alone was significantly greater in venous segments involved with nonobstructive thrombi than in those with obstructive thrombi (12 of 23 vs five of 51; P less than .005). Results were similar for the combination of rTPA and heparin (five of six vs six of 30, P less than .01). No significant difference was seen in the response of either obstructive or nonobstructive thrombus to heparin alone. Thrombotic tails responded substantially (greater than 50% decrease in size) to rTPA with or without heparin in 22 of 24 patients. The venographic appearance of DVT appears to help in predicting the therapeutic response to thrombolytic therapy.
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PMID:Short-term response to thrombolytic therapy in deep venous thrombosis: predictive value of venographic appearance. 162 Aug 26

We studied the thrombolytic dose-response relationship of a recombinant plasminogen activator (rPA) (BM 06.022) compared with alteplase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle 2 and protease domains of human tissue PA (tPA) and lacks oligosaccharide side chains because of its expression in Escherichia coli. Thrombus formation in anesthetized, open-chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery in the presence of a critical stenosis. Intravenous bolus injection of BM 06.022 (50, 100, 140, and 200 kU/kg) or of alteplase (200, 800, 1,130, and 1,600 kU/kg) 30 min after coronary occlusion to six heparinized dogs per group achieved a dose-dependent increase in reperfusion rate and decrease in residual thrombus wet weight. Vehicle-treated dogs did not reperfuse. Semilogarithmic regression analysis showed that the effective dose that produced 50% reperfusion of BM 06.022 (83 kU/kg) was 11.6-fold lower than that of alteplase (951 kU/kg). Comparison with infusion experiments showed that intravenous bolus injection of 140 kU/kg of BM 06.022 was equieffective to a 90-min infusion of 800 kU/kg (= 1 mg/kg) of alteplase as a standard treatment regarding reperfusion rate (66%) and time to reperfusion (15 +/- 6 vs. 18 +/- 8 min). Pharmacokinetic analysis for functionally active BM 06.022 or alteplase in plasma revealed a total plasma clearance of 4.1-6.6 ml/min/kg for BM 06.022 and of 12.6-42.3 ml/min/kg for alteplase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary thrombolytic properties of a novel recombinant plasminogen activator (BM 06.022) in a canine model. 171 79

The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of thrombolytic and systemic effects of the novel recombinant plasminogen activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. 173 72

Thrombus removal using percutaneous rotational thrombectomy (PRT), followed by tissue plasminogen activator (t-PA), was studied by contrast angiography and fiberoptic angioscopy in a canine femoral artery model of thrombosis. After thrombus induction and following each treatment, comparisons were made between angioscopy and angiography for the detection of thrombus and subintimal dissection. Angioscopic images were scored in a blinded fashion for lining, protruding, or occlusive thrombus (class 1,2, or 3) as well as estimated wall coverage by thrombus. Angiograms were studied for percent diameter stenosis and the presence of flaps. Following external forceps crush injury of 18 arteries, two hour occlusion, and injection of thrombin, mean angiographic stenosis was 66%, thrombus coverage by angioscopy was 81%, and mean angioscopy class was 2.5. Following PRT, stenosis decreased to 27% (p less than 0.008), thrombus coverage was reduced to 49% (p less than 0.02), and angioscopy class dropped to 2.0 (p less than 0.07). After t-PA treatment, these values were further reduced to 25% (p = NS), 26% (p less than 0.02), and 1.3 (p less than 0.008), respectively. In comparison to angiography, subintimal dissection (seen as flaps) and thrombus (lining, protruding, or occlusive) were present significantly more often by angioscopy (p less than 0.001). It is concluded that PRT results in significant thrombolysis, apparent by angiography and angioscopy. Follow-up t-PA can produce additional, incremental thrombolysis, apparent only by angioscopy. A beneficial role for t-PA following mechanical thrombolysis is suggested by this model. The superior sensitivity of angioscopy for detection of flaps and thrombus is underscored by this study.
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PMID:Thrombolysis by rotational thrombectomy followed by tissue plasminogen activator: evaluation by angioscopy. 176 46

Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).
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PMID:Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. 190 61

Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n = 10) served as the control, receiving the saline diluent, and group 2 (n = 9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24 +/- 2 to 10 +/- 2 ml/min). Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p less than 0.05). Oscillations in coronary blood flow preceded rethrombosis in group 1, whereas 7E3 F(ab')2 stabilized left circumflex coronary artery blood flow patterns during the course of teh experimental protocol (5.2 +/- 0.9 vs. 0.7 +/- 0.4 oscillations, respectively; p less than 0.05). Thrombus mass recovered from the left circumflex coronary artery at the conclusion of each experiment was greater in group 1 as compared with group 2 (7.0 +/- 2.3 vs. 1.5 +/- 0.7 mg, respectively; p less than 0.05). The area of left ventricle at risk for infarction was similar in both groups but infarct size, infarction/at risk assessed histochemically, was larger in group 1 than group 2 (35 +/- 9% vs. 6 +/- 4%, respectively; p less than 0.05). Platelet aggregation induced by ADP and arachidonic acid was similar at baseline for all of the animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model. 210 75


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