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)

A new European Cooperative Study Group trial of 721 patients has recently found recombinant tissue-type plasminogen activator (rt-PA) to positively affect infarct size, left ventricular function, cardiovascular morbidity and early survival. In this 26 center trial, patients were randomized to receive either placebo or 100 mg rt-PA intravenously over 3 h. Heparin (5,000 U bolus injection and then 1,000 U/h) and aspirin (250 mg initially, then 75 to 125 mg every other day) were given to all patients until angiography was performed (10 to 22 days after allocation). Enzymatic infarct size was found to be 20% smaller in the rt-PA group (2p = 0.0018) than in the control group. At angiography, 83% of rt-PA-treated patients had a patent infarct-related vessel compared with 77% of the placebo-treated patients. Ejection fraction was 2.2% points higher (2p = 0.04) and end-diastolic and end-systolic volumes were +/- 6 ml smaller (2p = 0.003) than in the control group, indicating an improved left ventricular pump function in the thrombolysis group. Cardiovascular complications such as shock, ventricular fibrillation and pericarditis were markedly fewer in patients treated with rt-PA, but bleeding complications occurred more frequently. An intracranial hemorrhage within 3 days after the infusion of rt-PA was observed in five patients (1.4%). None of these bleeding episodes was causally related to death. Although this European Cooperative trial was not designed primarily as a mortality study, important reductions in early mortality rates were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lessons from the European Cooperative recombinant tissue-type plasminogen activator (rt-PA) versus placebo trial. 314 43

Pulmonary embolism remains a challenging problem in diagnosis and management for the emergency physician. Although its clinical presentation is protean and often ambiguous, risk stratification can be accomplished based on the predictive power of a limited number of physical and historical characteristics. Ventilation-perfusion lung scanning occupies a central position in the work-up of suspected PE; however, evidence exists that it may be misused by many physicians. A low probability V-Q scan does not exclude the diagnosis of PE. Patients with other than normal- or high-probability patterns of pulmonary ventilation and perfusion on lung scanning require further investigation. Noninvasive venous studies are useful when indicative of proximal deep venous thrombosis, but are normal in many patients with acute PE. Heparin remains the standard of treatment for most patients with PE. Vena cava filters effectively reduce the incidence of recurrent PE in patients with contraindications to anticoagulation. Thrombolytic therapy offers potential advantages in the treatment of patients with shock due to their PE. Case reports of PE treated with tissue-type plasminogen activator, a new thrombus-specific fibrinolytic agent, are encouraging but preliminary.
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PMID:Pulmonary embolism. 328 Mar 1

Heparin or heparin-like substances have been described to induce the release of plasminogen activator (PA) activity in different animal perfusion models. In this paper we report that Dermatan Sulphate (DS) is able to induce PA activity release in the perfused rat hindquarters. Perfusion of different doses of DS (0.1 to 0.8 mg/mL) stimulates a release of PA activity that is maximum after the initial two minutes of perfusion. The amount of PA activity released rises progressively within a certain concentration range of DS (0.1 to 0.4 mg/mL) and declines thereafter (0.6 to 0.8 mg/mL). The type of PA activity increased during DS perfusion was characterized by SDS-PAGE and fibrin autography as tissue-type PA (t-PA) on the basis of its mol wt (67,000 d) and inhibition by a specific anti t-PA antiserum. This effect might be considered as potentially contributing to the antithrombotic activity of DS, at least at the local level.
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PMID:Dermatan sulphate induces plasminogen activator release in the perfused rat hindquarters. 367 16

The response of components of the coagulation and fibrinolytic systems has been examined in patients undergoing minor and major elective surgery and receiving or not receiving subcutaneously administered prophylactic low molecular weight (LMW) heparin. Blood samples were withdrawn pre-operation (PO), post-anaesthesia (PA), during operation (DO) and 24 hours post-operation. Release of plasminogen activator occurred post anaesthesia at a time when factor VIII components were unchanged or decreased. Induction of anaesthesia decreased plasminogen (p less than 0.005) fibrinogen (p less than 0.02) ATIII (p less than 0.002) and fast a2-antiplasmin (p less than 0.005). During operation plasminogen activator release reached a peak in association with a moderate increase in factor VIII components. Heparin treatment produced a prolongation of APTT at DO (p less than 0.05) and at 24hr (p less than 0.002) stages, this prolongation being apparently unrelated to its concentration but did not prevent the rise of factor VIII components observed at 24 hr (p less than 0.02). Prekallikrein (p less than 0.05) and antithrombin III levels (p less than 0.05) were significantly higher whereas fast a2-antiplasmin (p less than 0.002) was significantly lower at 24 hours in patients undergoing major operation and treated with heparin. Protein C levels fell significantly at 24 hours in the untreated patient (p less than 0.014) and in the heparin treated group the fall was greater than the control group (p less than 0.007). At 24 hours other haemostatic and fibrinolytic components were unaffected by heparin treatment.
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PMID:The influence of LMW heparin on the coagulation and fibrinolytic response to surgery. 392 Jul 75

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding.
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PMID:Significance of intravascular coagulation and fibrinolysis in acute hepatic failure. 482 Jun 41

Spontaneously released plasminogen activator after perfusion with 0.9% NaCl of isolated pig ear was purified by affinity chromatography on Heparin-Sepharose. The molecular weight of the plasminogen activator is about 60,000 Daltons, the isoelectric point lies at pH 7.6. The enzyme is most stable at neutral pH. At 37 degrees C it is stable for two hours. The activator did not show lytic activity either on heated or on PAMBA fibrin plates. The activity of the activator was inhibited by exposure to DFP and PMSF but not by exposure to TLCK and TPCK, suggesting that it is an enzyme with an active-site residue which belongs to the tissue-type activators.
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PMID:Characterisation of the vascular plasminogen activator from the pig ear. 608 62

Activated protein C is a vitamin K-dependent plasma protein which inhibits blood coagulation at the levels of factors V and VIII in the clotting cascade and which enhances blood clot lysis by raising the levels of circulating plasminogen activator. Activation of protein C occurs when thrombin binds to an endothelial cell associated cofactor, thrombomodulin. The thrombin-thrombomodulin complex rapidly activates the protein C. The activated protein C has a relatively long half-life in plasma and thus can serve as a circulating anticoagulant as well as elevate the levels of plasminogen activator. Heparin interacts with the protein C system in at least two distinct ways. First, the activation of protein C in vivo can be blocked by administration of low levels of heparin. The heparin brings about the inhibition of thrombin either before thrombin is bound to the cell-associated thrombomodulin or after the thrombin is complexed to the thrombomodulin. Secondly, activated protein C has its own unique inhibitor, activated protein C inhibitor. Inhibition of activated protein C by this inhibitor is stimulated by relatively high levels of heparin (5-10 u/ml). The physiologic significance of heparin-activated protein C inhibitor remains to be demonstrated.
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PMID:Heparin-protein C interaction. 608 2

Balb/c 3T3 cultures grown in the absence of serum release both plasminogen activator and plasminogen activator inhibitor in the culture medium. Cellular transformation with SV-40 virus increased the level of the activator, whereas dexamethasone increased the level of the inhibitor. Heparin added to the medium potentiated the glucocorticoid-induced inhibitory activity, strongly decreasing or completely abolishing the activity of plasminogen activator. Heparin sulfate showed similar effects to heparin, although at higher concentrations. It is suggested that heparin-like compounds are involved in the regulation of plasminogen activator, acting as inhibitory cofactors.
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PMID:Cooperative effect of exogenous heparin-like compounds and secreted glucocorticoid-induced inhibitor on plasminogen activator in 3T3 cell cultures. 643 23

Blood shed into a closed peritoneal cavity is incoagulable. We have investigated this poorly understood phenomenon in animal experiments. Nonthrombogenic femoral vein-peritoneal cavity shunts were established in five dogs and 10 ml/kg blood admixed with 125I-dog fibrinogen was rapidly drained into the peritoneal cavity. After 1 hr the peritoneal cavity was entered and incoagulable blood aspirated; 125I-fibrinogen Mr distribution was assessed by AGPC, demonstrating complete degradation of fibrinogen into core fragments D and E with no evidence of soluble fibrin complexes or crosslinked fibrin fragments. Peritoneal cavity clotting factors II, V, and VIII and platelets were sharply reduced compared to venous control samples. Plasminogen and antiplasmin levels in peritoneal cavity blood showed mean declines of 17% and 15%, respectively. By comparison, incubation of dog blood with 1 to 2 X 10(3) U/ml urokinase for 1 hr in vitro was insufficient to degrade 125I-dog fibrinogen to core fragments D and E, although plasminogen and antiplasmin were reduced by 66% and 100%, respectively. Pretreatment of dogs with epsilon ACA (0.13 gm/kg, N = 4) resulted in massive intraperitoneal cavity clotting, and aspirated fluid blood contained only small quantities of radiolabel. Heparin treatment (300 U/kg bolus, 150 U/kg/hr infusion; N = 4) eliminated the peritoneal cavity lytic response; analytical gel permeation chromatography consistently demonstrated intact fibrinogen only. Therefore it is apparent that blood in a closed peritoneal cavity undergoes limited clotting followed by brisk plasmin-mediated fibrinolysis as opposed to fibrinogenolysis. The closed peritoneal cavity fibrinolytic response to clotting blood represents a striking example of the efficiency of the "tissue-type" plasminogen activator.
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PMID:Peritoneal fibrinolysis: evidence for the efficiency of the tissue-type plasminogen activator. 668 80

Using modeling of heparin-fibroblast growth factor interactions, we replaced four basic residues of basic fibroblast growth factor (FGF-2) with neutral glutamine residues by site-specific mutagenesis to give the mutants K128Q, K138Q, K128Q-K138Q, R129Q, K134Q, and R129Q-K134Q. The FGF mutants were characterized for their receptor and heparin binding affinities, mitogenic and cell proliferation activities, and their ability to induce plasminogen activator (PA) production and in vitro angiogenesis by cultured endothelial cells. Heparin binding properties and biological activities of the three mutants involving R129 and K134 remained essentially unchanged; however, significant changes for three mutants involving K128 and K138 were found. The KD values for heparin binding for K128Q and K138Q mutants were increased about 10-fold, and that for the K128Q-K138Q double mutant was increased by about 100-fold. The mutant K128Q-K138Q required a 10-fold higher concentration of heparin to promote binding to heparan sulfate proteoglycan (HSPG)-deficient CHO cells transfected with fibroblast growth factor receptor-1 (FGFR1) or to induce DNA synthesis in HSPG-deficient myeloid cells transfected with FGFR1. Binding affinities of the mutants to cell surface receptors on BHK-21 cells, however, were similar to that of wild-type FGF-2. In endothelial cell proliferation assays the activities of K128Q and K128Q-K138Q were about 10-fold lower than that of the wild-type protein, whereas the K138Q mutant exhibited wild-type activity. In addition, the K128Q-K138Q mutant displayed a markedly lowered capacity to induce PA activity in cultured endothelial cells and to form capillary-like structures in an in vitro angiogenesis model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diminished heparin binding of a basic fibroblast growth factor mutant is associated with reduced receptor binding, mitogenesis, plasminogen activator induction, and in vitro angiogenesis. 752 51


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