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

Animal studies have demonstrated that thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is accelerated and that bleeding is reduced when rt-PA is infused over a short period. Previous clinical studies in patients with venous thromboembolism have shown that rt-PA is an effective thrombolytic agent when administered by continuous infusion over 2 to 24 hours. Clinical experience of bolus rt-PA administration in patients with massive acute pulmonary embolism (PE) is, however, limited. A prospective open study was conducted in which 54 patients with massive PE (Miller index > or = 20 of 34) received a 10-minute infusion of rt-PA at a dose of 1 mg/kg. Perfusion lung scanning was used to assess the change in pulmonary perfusion after drug administration. At 48 hours and 10 days, the mean absolute improvements in the perfusion defect were 11 and 31%, respectively. In addition, a significant clinical improvement occurred within 2 hours in 11 of the 15 shocked patients. Five patients died (9%) as a result of persistent shock (3 patients), neurologic damage (1 patient) or intracranial bleeding (1 patient). Major bleeding occurred in 8 patients (15%). Long-term follow-up information was available for 44 of the 49 discharged patients: 2 had died and 12 (27%) complained of persistent exertional dyspnea, 7 of whom had an associated heart or lung disease or chronic thromboembolism at admission. These results suggest that a bolus regimen of rt-PA could provide a convenient approach to thrombolytic therapy in patients with massive PE.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Cardiol 1992 Dec 01
PMID:Effectiveness and safety of bolus administration of alteplase in massive pulmonary embolism. 144 21

This article has summarized known congenital and acquired alterations of hemostasis leading to thrombosis. Decreases in coagulation inhibitors, including antithrombin III, heparin cofactor II, and protein C and protein S, are of major importance in assessing patients with hypercoagulable states or patients with unexplained thrombosis. Newer assays for components of the fibrinolytic system, plasminogen, t-PA and t-PA inhibitor are also now readily available and are important for defining congenital or acquired fibrinolytic defects leading to hypercoagulability and thrombosis. By judicious use of these assays, combined with clinical evaluation, many patients with thrombosis will have an underlying etiologic blood protein defect defined. Delineating reasons for a thrombotic event is of obvious importance for planning long-term prophylactic therapy and for diagnosing and counseling afflicted family members. In this manner, newly found patients can be treated prophylactically before unalterable morbidity or mortality occurs.
Hematol Oncol Clin North Am 1992 Dec
PMID:Hypercoagulability and thrombosis. 145 21

Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up.
Am Heart J 1992 Dec
PMID:Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group. 146 94

Plasminogen, the zymogen form of the fibrinolytic enzyme plasmin, is known to undergo plasmin-mediated modification in vitro. The modified form, Lys-plasminogen, is superior to the native Glu-plasminogen in fibrin binding and as a substrate for activation by tissue-type plasminogen activator (t-PA). The present study was undertaken to determine the existence and significance of the Glu- to Lys-plasminogen conversion during t-PA-mediated lysis of plasma clots in vitro. When human plasma was supplemented with exogenous Lys-plasminogen and clotted, a dose-dependent shortening of lysis time was observed. Formation of Lys-plasminogen in situ during fibrinolysis was determined using 131I-Glu-plasminogen-supplemented plasma. By the time of lysis, Lys-plasminogen had accumulated to about 20% of the initial concentration of Glu-plasminogen. Quantitation of activation of both Glu- and Lys-plasminogen as well as the conversion of Glu- to Lys-plasminogen in plasma supplemented with both 131I-Glu-plasminogen and 125I-Lys-plasminogen was accomplished by determining the flux of the isotopically labeled species along three pathways: Glu-plasminogen-->Glu-plasmin, Glu-plasminogen-->Lys-plasminogen, and Lys-plasminogen-->Lys-plasmin. After a brief lag, the Glu-plasminogen activation rate was constant until lysis was achieved, at which point activation ceased. The Lys-plasminogen activation rate also was essentially constant until lysis but was not characterized by a lag phase. The rate of conversion of Glu- to Lys-plasminogen was nonlinear and correlated directly with the rate of fibrinolysis. By the time lysis had occurred, Glu-plasminogen consumption had been distributed equally between direct activation to plasmin and conversion to Lys-plasminogen, and 45% of the plasmin which had been formed was derived from Lys-plasminogen. These results demonstrate both the formation and the subsequent activation of Lys-plasminogen during fibrinolysis. As a result of improved fibrin binding and activation of Lys-plasminogen compared to Glu-plasminogen, the formation of Lys-plasminogen within a clot constitutes a positive feedback mechanism that can further stimulate the activation of plasminogen by t-PA as fibrinolysis progresses.
J Biol Chem 1992 Dec 25
PMID:Lys-plasminogen is a significant intermediate in the activation of Glu-plasminogen during fibrinolysis in vitro. 146 25

Cyclosporine treatment has been associated with thrombotic vascular complications. We investigated the activity of the fibrinolytic system and its capacity to respond upon DDAVP stimulation in a group of 20 cyclosporine-treated patients as compared with a group of 9 azathioprine-treated patients. Furthermore, the effect of the administration of fish-oil to these patients on the endogenous fibrinolytic activity was studied in a double-blind randomized, placebo-controlled cross-over study. The cyclosporine-treated patients showed a significantly reduced plasminogen activator activity and plasmin generation response upon the infusion of DDAVP as compared with the azathioprine group. In the cyclosporine group 60% of the patients had an impaired fibrinolytic response, whereas this was found in only 11% of the azathioprine-treated patients (P < 0.05). The impairment of the endogenous fibrinolysis activity could be attributed either to a defective release of plasminogen activator from the vessel wall (67% of patients) or to high plasma levels of plasminogen activator inhibitor 1 (33% of patients). Administration of fish-oil resulted in a significant improvement of the impaired fibrinolysis in the cyclosporine group. Particularly, in patients with a defective release of plasminogen activator from the vessel wall, fish-oil treatment resulted in a normalization of the fibrinolytic activity. These results indicate that cyclosporine treatment induces an impaired fibrinolysis that may contribute to the frequent occurrence of thromboembolic complications and eventually the impairment of renal function in cyclosporine-treated patients. The beneficial effect of the administration of fish-oil on the endogenous fibrinolysis may result in a reduction of the adverse events associated with cyclosporine treatment.
Transplantation 1992 Dec
PMID:Impaired fibrinolysis in cyclosporine-treated renal transplant patients. Analysis of the defect and beneficial effect of fish-oil. 146 91

Structural analysis of enzymically released N-linked carbohydrate chains of human urokinase (urinary-type plasminogen activator) by 1H NMR spectroscopy and FAB-MS demonstrated that the N-linked oligosaccharides on the only N-glycosylation site contain diantennary structures with the novel GalNAc beta (1-4) [Fuc alpha (1-3)]GlcNAc beta (1-2) element in the upper or the lower branch.
FEBS Lett 1992 Dec 21
PMID:Human urokinase contains GalNAc beta (1-4)[Fuc alpha (1-3)]GlcNAc beta (1-2) as a novel terminal element in N-linked carbohydrate chains. 146 73

The relative efficacy and safety of individual thrombolytic agents, administered alone and with antiplatelet and antithrombotic drugs, in the treatment of acute myocardial infarction are presented. The clinical benefits and risks of treatment choices are discussed in relation to the mechanisms of the formation and prevention of thrombus and thrombolysis. It is concluded that streptokinase, tissue plasminogen activator (t-PA), and anisoylated plasminogen-streptokinase activator complex (APSAC) significantly reduce mortality and improve left ventricular function equally, despite differences in the rate at which they achieve vascular patency, their durations of action, and the extent to which their use is associated with adverse events. The questions of how best to minimize reocclusion/reinfarction, bleeding, and stroke are discussed, with particular focus on the beneficial use of aspirin and the unresolved issue of how best to use heparin.
Am J Cardiol 1992 Dec 21
PMID:Thrombolytic, antiplatelet, and antithrombotic agents. 147 1

alpha 2-antiplasmin (alpha 2-AP) exerts its inhibitory effect on fibrinolysis by rapidly inhibiting the plasmin evolved; in addition, it has been suggested that interference with the binding of plasminogen to fibrin, a function shared with histidine-rich glycoprotein (HRGP), may also be significant in inhibition of fibrinolysis. To elucidate if plasminogen binding by these two alpha 2-globulins may decrease the generation of plasmin by tissue-type plasminogen activator (t-PA) at the surface of fibrin, a system mimicking the fibrin/plasma interface was used. Attempts were made to differentiate the plasminogen binding from the plasmin inhibitory function of alpha 2-AP. The activation of human Glu-plasminogen (native plasminogen with NH2-terminal glutamic acid) by fibrin-bound t-PA was performed in a plasma environment using either normal plasma, alpha 2-AP- or HRGP-depleted plasmas supplemented with increasing amounts of the lacking protein, or in a reconstituted system with purified plasminogen and various concentrations of alpha 2-AP and HRGP. The activation of Glu-plasminogen in alpha 2-AP-depleted plasma containing a normal concentration of HRGP produced a time-dependent increase in the generation of plasmin. The addition of 1 microM-alpha 2-AP to this plasma prevented the formation of Lys-derivatives and produced a marked decrease (42%) in the number of plasminogen-binding sites. In contrast, the addition of 1.5 microM-HRGP to HRGP-depleted plasma containing a normal amount of alpha 2-AP produced only a modest (17%) decrease in the amount of plasmin(ogen) bound. Moreover, in a purified system the amount of plasminogen-binding sites and thereby of plasmin generated at the surface of fibrin in the presence of both alpha-2 globulins was similar to the amount generated in the presence of alpha 2-AP alone. These results indicate clearly that the formation of reversible complexes between plasminogen and alpha 2-AP does not interfere with the binding and activation of plasminogen at the fibrin surface. In contrast, the inhibition of plasmin by alpha 2-AP decreases importantly the number of plasminogen-binding sites (carboxyl-terminal lysines) and inhibits thereby the accelerated phase of fibrinolysis. It can be concluded that interference of the binding of plasminogen to fibrin by alpha 2-AP during plasminogen activation, does not play a significant role in inhibition of fibrinolysis, and that the plasminogen-binding effect of HRGP, if any, is obscured by the important inhibitory effect of alpha 2-AP.
Biochim Biophys Acta 1992 Dec 08
PMID:Plasminogen binding by alpha 2-antiplasmin and histidine-rich glycoprotein does not inhibit plasminogen activation at the surface of fibrin. 147 36

The role of aspirin on tissue plasminogen activator (t-PA) release was studied in rats after experimental venous occlusion. For this purpose, we developed a new experimental model which combines a vascular perfusion system (isolated rat hindquarters) with vascular stimulation, namely the application of venous stasis. Application of venous stasis for 30 min induced the release of t-PA from the vascular endothelium into the perfusate (from 0.19 +/- 0.05 to 0.39 +/- 0.05 UI/ml), reaching a peak 90 s after reperfusion. Aspirin administered to rats 60 min before the experiments (100 mg/kg i.v.), or dissolved in Tyrode solution (100 microM), suppressed 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthesis (0.38 +/- 0.09 in control and < 0.01 and 0.15 +/- 0.09 ng/ml, respectively, in aspirin-treated groups) but did not prevent the increase in fibrinolytic activity after venous occlusion (from 0.20 +/- 0.04 to 0.38 +/- 0.06 and from 0.07 +/- 0.03 to 0.27 +/- 0.03 IU/ml, respectively, in the aspirin-treated group). Our results suggest that the increase in fibrinolytic activity after experimental venous occlusion in isolated rat hindlegs is modulated by mechanism(s) other than the cyclooxygenase pathway in the vascular wall.
Eur J Pharmacol 1992 Dec 08
PMID:Effect of aspirin on the fibrinolytic response in perfused rat hindquarters. 147 62

An experiment was conducted to determine whether morphological and functional characteristics of follicles differed at a similar stage of pubertal (first) and third estrus in the same gilts. Nine prepubertal gilts were checked three times daily for estrus and laparotomized 6 h after detected first and third estrus. Samples of vena cava and ovarian venous blood were collected, follicle numbers and diameters were recorded, and follicular fluid (FF) was aspirated from all follicles 8 to 12 mm in diameter. Sera and(or) FF were analyzed for progesterone (P4), estradiol-17 beta (E2), testosterone (T), androstenedione (A4), 5 alpha-dihydrotestosterone (DHT), plasminogen activator (PA), and plasmin (PLM). Overall mean number of follicles > or = 8 mm in diameter did not differ between gilts at first and third estrus (P > .05) but gilts at first estrus had more follicles 4 to 8 (P < .05) and 8.1 to 10 mm in diameter (P < .01) and fewer 10.1 to 12 mm in diameter (P < .07) than at third estrus. Mean FF concentrations of E2, T, and A4 at third estrus were significantly greater than at first estrus, whereas FF concentrations of P4, DHT, PA, and PLM were similar at first and third estrus (P > .05). Mean concentrations of E2 in systemic and ovarian venous sera were also greater in gilts at third than at first estrus (both P < .05). Systemic concentrations of P4 in gilts at first and third estrus did not differ (P > .05).(ABSTRACT TRUNCATED AT 250 WORDS)
J Anim Sci 1992 Dec
PMID:Steroids and plasminogen activator concentrations in follicular fluid of gilts at first and third estrus. 147 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>