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 cytokine that inhibits fibrinolysis has been detected in the serum-free culture medium of guinea pig and hamster fibroblasts. This proteinase inhibitor was also present in Triton X-100 extracts of guinea pig cells. It was stable at pH 3.0 for 2 hr and was produced by cells rather than assimilated from serum in the culture medium as evidenced by: (a) an apparent molecular size (less than 45 kilodaltons) less than that of the principal serum-derived proteinase inhibitors; (b) its continued secretion after several passages of the cells in serum-free medium; and (c) the lack of inhibitory activity in the medium of mitomycin C-treated cells. The cytokine inhibited the proteinase activity of human urokinase, soluble TPA-stimulated guinea pig plasminogen activator, and the cell-associated plasminogen activator of tumorigenic guinea pig cells. Soluble plasminogen activator appeared to be inhibited to a greater degree than the cell-associated enzyme. The fluorogenic substrate (7-(N-carbobenzoxyglycylglycylargininamido)-4-methylcoumarin was used in a direct assay of proteinase activity and demonstrated that the cytokine inhibited both plasminogen activator and plasmin, the two proteinases of the fibrinolytic cascade. Tumorigenic guinea pig and hamster fibroblasts as well as nontransformed guinea pig fibroblasts were found to produce the inhibitory cytokine, and the amount of inhibitor secreted was independent of the tumorigenic potential of the cells. Production of the inhibitor by normal cells may be related to contact inhibition of growth, and this cytokine may contribute to the fine regulation of local proteolysis within tissues.
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PMID:Secretion of proteinase inhibitors by tumorigenic and nontumorigenic guinea pig and Syrian hamster fibroblasts: evidence for autocrine regulation of local proteolysis. 642 73

Phorbol and eight of its derivatives were investigated for their ability to stimulate the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts and to aggregate human blood platelets and have been assayed for tumor, promoting and skin, irritant activities. Over a range of concentrations, elevation in the levels of plasminogen activator activity induced by phorbol derivatives correlates well with their promoting and irritant properties. In the platelet aggregation assay however, the parallelism between the activities measured in different biological assays was less complete. While strong promoters, such as TPA, are potent aggregating agents, and weak promoters, such as PDA, are poor or ineffective inducers of aggregation, two derivatives, PDD and PDB, deviate from this general result. Platelets must be exposed to PDD in relatively high concentrations before they will aggregate, and PDB was found to be the most potent aggregating agent of all the derivatives tested.
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PMID:Plasminogen activator induction and platelet aggregation by phorbol and some of its derivatives: correlation with skin irritancy and tumor-promoting activity. 719 86

Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. Since in aging and in atherosclerosis the changes observed in the endothelium resemble those of in vitro aged endothelial cells, we have examined the expression of PAI-1 in cells at different population doublings. In senescent endothelial cells, PAI-1 mRNA and protein are constitutively high, but uninducible by exogenous interleukin 1 alpha as well as by the phorbol ester TPA. Interestingly the increase of PAI-1 levels correlates with the upregulation of interleukin 1 alpha, which characterizes endothelial cell senescence. Since PAI-1 expression is not increased in young cells made nondividing by contact inhibition, we anticipate that PAI-1 expression can be used as an appropriate marker of endothelial senescence. Moreover, PAI-1 was not upregulated in senescent or in progeric human fibroblasts, which do not overexpress interleukin 1 alpha, thus suggesting that multiple pathways may exist to regulate aging of human fibroblasts and endothelial cells.
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PMID:Senescence-dependent regulation of type 1 plasminogen activator inhibitor in human vascular endothelial cells. 762 47

Because timing of sampling is crucial in an investigation of the effects of labor and delivery on fibrinolysis we conducted a study of fibrinolytic markers in plasma of 10 healthy multiparous women in whom labor was induced, which allowed standardization of sampling times in relation to the course of labor and delivery. Blood samples were taken 5 min before the start of oxytocin infusion, at full cervical dilatation, and within 5 min after delivery of the placenta. A sample of mixed free flowing cord blood was obtained after delivery with the placenta in situ. Variables determined were tissue-type plasminogen-activator (t-PA) and the plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). The only significant change between the beginning of the induction of labor and the end of the first stage of labor was a rise in t-PA antigen (P = 0.01). All variables, except PAI-2 antigen, changed significantly after delivery of the placenta: t-PA antigen and activity showed a rise (P < 0.05), accompanied by a fall in PAI-1 antigen and activity (P < 0.01). T-PA activity in cord plasma was higher (P < 0.01) in comparison with maternal plasma concentrations at the end of the first stage of labor, t-PA antigen levels were similar, and PAI-1 antigen and activity and PAI-2 antigen were lower in cord plasma (P < 0.001). Our study shows that activation of the maternal fibrinolytic system can already be detected during labor, with a marked further increase in fibrinolytic potential after placental separation.
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PMID:Effects of labor and delivery on fibrinolysis. 795 59

Pulmonary fibrin deposition suggests the involvement of coagulation and fibrinolysis in pulmonary inflammation. The present study was designed to investigate the alterations of coagulation and fibrinolysis in rabbits that received thoracic irradiation. Serial bronchoalveolar lavage (BAL) was performed after the irradiation, and procoagulant activity (PCA) and tissue plasminogen activator (t-PA) were measured in BAL fluids. PCA increased from 2 to 8 weeks after irradiation with increased number of macrophages and increased PCA per macrophage. T-PA also increased with a significant difference at 4 weeks compared to controls. Although irradiation activated both PCA and t-PA, PCA increased prior to t-PA and the elevation lasted longer. It was concluded that activation of the coagulation system promotes pulmonary fibrin deposition and may contribute to the progression of pulmonary injury.
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PMID:[Coagulation and fibrinolysis systems in bronchoalveolar lavage fluid in irradiated lung of rabbits]. 812 Oct 87

The purpose of this study was to compare vascular damage and thrombus formation in the coronary and femoral arteries after balloon angioplasty, and to develop a physiological animal model of intracoronary occlusive thrombus using the balloon angioplasty technique. Angioplasty of the left anterior descending coronary arteries of 14 dogs was performed with an oversized balloon catheter at a high inflation pressure (150 PSI). This was followed angiographically (PTCA protocol). Dogs that showed arterial occlusion were divided into 2 groups. The dogs in 1 group were killed with an overdose of sodium pentobarbital, and those in the other group were infused with a tissue-type plasminogen activator (t-PA; 300,000 unit/kg). Angioplasty of the femoral and profunda femoris arteries (n = 5) was performed in 5 other dogs (PTA protocol). All of the animals were eventually sacrificed and tissue preparations were made from all 3 types of arteries. In the PTCA protocol, acute arterial occlusion was seen angiographically within 2 h in 10 of the 14 dogs. A histological study of the acutely occluded arteries (n = 5) showed thrombotic occlusion and severe arterial damage with medial tearing. T-PA was infused to 5 of the dogs with acute occlusion, and all showed reperfusion. A histological study of these animals showed severe arterial damage, but no macroscopic thrombus. In 4 dogs without acute occlusion, none of the 10 arteries examined were acutely occluded. In the PTA protocol, none of the 10 arteries were acutely occluded. A histological study showed fewer thrombi and less severe arterial damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An animal model of coronary thrombosis and thrombolysis--comparisons of vascular damage and thrombus formation in the coronary and femoral arteries after balloon angioplasty. 823 Jun 71

Tissue-type plasminogen activator (t-PA) is a potent and efficacious mitogen for growth-arrested cultured human aortic smooth muscle cells, stimulating an increase in cell number at 0.3-30 nM concentration. Double-chain t-PA is as efficient as single-chain t-PA in stimulating smooth muscle cell mitogenesis, whereas single-chain urokinase-type plasminogen activator (u-PA) or u-PA and plasmin or plasminogen are ineffective. Plasminogen activator inhibitor-1, Pefabloc-TPA, diisopropyl fluorophosphate or alpha 1-anti-trypsin inhibit the mitogenic effect of t-PA for smooth muscle cells in a dose-dependent manner, showing that it is dependent on the enzymatic activity. t-PA activated phosphoinositide turnover in smooth muscle cells through a pertussis toxin-insensitive pathway and stimulated proto-oncogene c-fos and c-jun mRNA levels. These findings indicate that t-PA stimulates vascular human smooth muscle cell proliferation and suggest for the first time that it may contribute to intimal smooth muscle cell proliferation after vascular injury as a result of angioplasty or vascular compromise during atherogenesis.
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PMID:Tissue-type plasminogen activator is a potent mitogen for human aortic smooth muscle cells. 830 Jun 42

Triaging patients suspected of myocardial infarction is performed primarily in the coronary care unit, with infarction determined within 12 to 24 hours, and only about 20% are subsequently shown to have myocardial infarction. Plasma MB CK is not elevated until 8 to 10 hours after onset, and the ECG is unreliable; thus, the need has arisen for a new "diagnostic mind-set." The need is threefold: (1) more effective triaging in the emergency room to prevent unnecessary use of hospital beds, particularly those in the intensive care units, (2) to administer thrombolytic therapy in the early hours, and (3) earlier detection of coronary reocclusion and reinfarction. Diagnostic imaging techniques such as pyrophosphate, thallium-201 technetium sestamibi, or positron emitting agents lack the necessary early diagnostic specificity, but echocardiography has potential although its specificity is limited. Plasma CK isoforms provide diagnostic sensitivity and specificity of 96% and 94%, respectively, within the initial 4 to 6 hours of onset and can be assayed within minutes. In a prospective study of 1100 patients suspected of infarction, with conventional MB CK, 22% of the patients admitted to the coronary care unit would have had infarction, whereas using the CK isoforms, 75% had infarction and about 50% were discharged home. A scenario for the future might be to initiate thrombolytic therapy outside the hospital (eg, recombinant tissue-type plasminogen activator [r-TPA] 20 mg bolus) and upon arrival, confirm or exclude infarction by the MB CK isoform which can be performed in the emergency room in 20 minutes to determine whether thrombolytic therapy and heparin should be continued.
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PMID:Earlier diagnosis and treatment of acute myocardial infarction necessitates the need for a 'new diagnostic mind-set'. 795 25

ELISA procedures are described for the quantitative analysis of the urokinase-type plasminogen activator (uPA) and of the tissue type PA (tPA). The assays were developed to detect the respective type of PA in cell culture supernatants. TPA can be present as a single-chain or a two-chain protein; uPA as pro-uPA, high or low molecular weight uPA, respectively. In addition, both PAs can be complexed with the plasminogen activator inhibitors PAI-I or PAI-2. Monoclonal antibodies specific for uPA or tPA were selected that recognized the distinct molecular forms of the PAs, even in the presence of fetal calf serum, which is a common--relatively ill-defined--ingredient of cell culture media. The test systems were found to be reliable, easy to perform, and to permit the detection of both types of PA in serum-free and serum-containing cell culture supernatants. Finally, the ELISA--in combination with functional tests--were used to analyse the different PA components in culture supernatants of uPA- or tPA-producing cell lines.
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PMID:Enzyme-linked immunosorbent assays for plasminogen activators. 831 89

This study assessed the short- and long-term effects of an energy-restrictive diet with or without exercise on plasminogen activator inhibitor-1 antigen (PAI-1 Ag) and PAI-1 activity, tissue-type plasminogen activator antigen (TPA Ag), and fibrinogen serum levels. Healthy, overweight postmenopausal women (age, 53.8+/-2.5 years; body mass index, 25 to 42 kg/m2; n=121) were randomly assigned to one of three groups: control, 4200-kJ/d diet, or 4200-kJ/d diet with combined aerobic and anaerobic exercise. PAI-1 activity and PAI-1 Ag, TPA Ag, and fibrinogen levels were measured at baseline, after a 12-week intervention, and after a further 6-month follow-up. PAI-1 Ag and activity and TPA Ag were positively correlated with serum triglyceride levels, the abdominal-to-total-body fat ratio (as assessed by total-body dual-energy x-ray absorptiometry), fasting blood glucose, and systolic BP and negatively with HDL cholesterol and sex hormone-binding globulin. The diet led to profound decreases and normalization of PAI-1 activity (approximately 50%), PAI-1 Ag (approximately 30%) and TPA Ag (approximately (29%), but exercise conferred no additional effect. Fibrinogen did not change. At follow-up there were no longer any significant changes (P>.05). In conclusion, PAI-1 Ag and activity as well as TPA Ag seem to be part of the metabolic syndrome X. The diet made the blood less thrombogenic in the short term with no effect of the added exercise.
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PMID:Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: Effect of dieting with or without exercise in overweight postmenopausal women. 863 Jun 63


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