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)

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

DNA damage results from a wide variety of external agents such as chemicals and radiation. The consequences of exposure to agents that damage DNA have been traditionally studied from the perspective of cell survival and mutagenesis. Mutations are late endpoints of DNA damage. Cells respond to the earlier stages of DNA damage by inducing the expression of several genes, including those specific of the nature of the lesion. These early transcriptional responses are likely to predetermine the later fate of the damaged cell. Genes activated during this early response include those involved in DNA repair, replication, and growth control. We are interested in the transcriptional mechanisms by which cells respond to DNA damaging agents. To facilitate the measurement of gene induction, we used seven different reporter constructs integrated stably into the RKO cell line derived from a human colon carcinoma. These constructs were derived from promoters and/or response elements isolated from genes associated with DNA damage responses in human cells, and were fused to the bacterial reporter gene, choramphenicol acetyl transferase (CAT). The cell lines generated in this manner contain the promoters and/or response elements representing DNA polymerase beta, p53, gadd (growth arrest and DNA damage) 45 and 153, c-fos, TPA response element, and tissue-type plasminogen activator. These recombinant cell lines were assembled in a 96-well microtiter plate permitting their simultaneous exposure to compounds and subsequent CAT protein measurement. This assembly has been designated the CAT-Tox (D) assay. These cell lines were exposed to different classes of DNA damaging agents including those which covalently join bases to form dimers (e.g., UVC irradiation), generate DNA adducts by alkylation (e.g., methylmethane sulfonate [MMS], ethylmethane sulfonate [EMS], N-methyl-N-nitro-N-nitrosoguanine [MNNG], dimethylnitrosamine [DMN]), cross-link DNA (e.g., mitomycin C), and inhibit DNA replication by intercalative (e.g., actinomycin D) and nonintercalative (e.g., hydroxyurea) mechanisms. The transcriptional responses were measured as a function of the accumulation of CAT protein using antibodies against CAT protein in a standard ELISA. Endogenous cellular responses were evaluated for a number of the genes represented in the assay at both the mRNA and protein levels by Northern and Western blot analysis, respectively. These data corroborate the stress-induced responses measured by CAT ELISA in the CAT-Tox (D) assay, demonstrating the usefulness of this assay as a rapid and sensitive method for detection of DNA damaging agents in human cells.
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PMID:Stress responses to DNA damaging agents in the human colon carcinoma cell line, RKO. 895 Mar 45

The role of heparin in conjunction with thrombolytic therapy for the management of patients with acute myocardial infarction continues to be controversial. Many issues, including the possible benefits and risks of this therapy, are unresolved. Administration of high-dose subcutaneous heparin in the presence of thrombolytic therapy results in a significant mortality reduction during the treatment period of 55 lives saved per 10,000 patients treated (p < 0.01). At 35 days mortality is not significantly decreased by 22 lives and 18 nonfatal infarctions, at a cost of 32 transfusions and 6 strokes (half of which result in full recovery) per 10,000 patients treated. There have been fewer than 1250 patients randomized in trials comparing intravenous heparin with no heparin in patients receiving thrombolytic therapy and aspirin. These trials are too small to draw reliable conclusions, although several trials have suggested that intravenous heparin is beneficial for maintaining patency after t-PA therapy. In the the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial, patients receiving streptokinase were randomized to receive either delayed subcutaneous heparin or intravenous heparin. There were no differences in clinical endpoints. However, despite 36% crossover to intravenous heparin among patients randomized to receive subcutaneous heparin with streptokinase, patency of the infarct-related artery was 17% higher (84% vs. 72%, p < 0.05) at 5-7 days in patients randomized to receive intravenous heparin and streptokinase. This significant difference could potentially translate into an important effect on long-term prognosis. Therapy for acute myocardial infarction should include aspirin and a thrombolytic agent for patients without contraindications. Based on the current evidence, it is reasonable to also administer intravenous heparin with either streptokinase or TPA.
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PMID:Is heparin of value in the management of acute myocardial infarction? 914 Jun 86

The plasminogen activator (PA) system is thought to play a major role in the proteolytic events associated with spermatogenesis. The mechanisms controlling the expression of PA and of its major physiological inhibitor, plasminogen activator inhibitor type-1 (PAI-1), in the seminiferous epithelium are still unknown. In the present study we analyzed the expression of PA and PAI-1 in a murine Sertoli cell line (42GPA9) in response to stimulation by lipopolysaccharides (LPS) used to activate the phagocytic activity of these cells. Immortalized Sertoli cells cultured under basal conditions secreted predominantly tissue-type PA (tPA) as demonstrated by zymographic analysis and the presence of tPA transcripts. In zymographic experiments a larger molecular weight proteolytic band corresponding to the formation of PA-PAI-1 complex was also observed. The stimulation of immortalized Sertoli cells by LPS resulted in both alteration of the apparent tPA molecular weight to a higher form and transient increase in PAI-1 biosynthesis. The phorbol ester TPA stimulates similarly PAI-1 synthesis in the Sertoli cell line, while 8-bromo-cAMP has no effect. These results suggest for the first time the existence of a direct linkage between molecular events triggered by phagocytosis and regulation of tPA and PAI-1 in Sertoli cells.
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PMID:Regulation of tissue-type plasminogen activator and its inhibitor (PAI-1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line. 1006 64

The present study compared the antithrombotic properties of fractionated aurin tricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (GP) Ib, and GR144053, a GPIIb/IIIa antagonist, in a hamster model of stenosis. Endothelial cell injury in the hamster carotid artery was achieved by a 2F modified catheter. Arterial blood flow in the control groups was interrupted 5.4+/-0.9 minutes after the injury. When ATA (0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg per hour) or GR144053 (0.1, 0.3, and 1.0 mg/kg per hour) were continuously infused intravenously, the time elapse before the vessel completely occluded was prolonged in a dose-dependent manner. However, all arteries in the ATA-treated groups ultimately occluded during the observation period even if the aggregation of platelets ex vivo and induced by botrocetin was completely inhibited. When either ATA (0.1 mg/kg per hour) or GR144053 (0.3 mg/kg per hour) were infused via an implanted osmotic pump together with tissue-type plasminogen activator (tPA), late patency of the reperfused artery was improved compared to that of arteries treated with TPA alone. However, the cyclic reflow pattern after reperfusion on days 0 and 1 was not reduced by the ATA treatment. The bleeding time was significantly prolonged when either ATA or GT144053 was coadministered with tPA. The treatment with ATA showed an especially marked prolongation of the bleeding time. In conclusion, both inhibition of platelet activation by ATA or GR144053 prevent arterial thrombosis and enhance the thrombolytic effect of tPA, but GR144053 was more protective in its antithrombotic effect and more effective during thrombolytic therapy than ATA.
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PMID:Comparison of the antithrombotic effects and bleeding risk of fractionated aurin tricarboxylic acid and the GPIIb/IIIa antagonist GR144053 in a hamster model of stenosis. 1040 86

One of the reasons of ventricular arrhythmias and coronary artery spasms in patients with acute myocardial infarction (AMI) may be the lower Na(+)-K(+)-ATPase activity, which causes decrease of potassium intracellular concentration and increase of calcium intracellular concentration. The aim of the study was the examination of the rate of sodium efflux through the lymphocytic cell membrane in patients with AMI after thrombolytic therapy. The survey was made in 50 patients with AMI after thrombolytic therapy: 30 of them with reperfusion (group I) and 20 without reperfusion (group II). The control group consisted of 31 healthy persons. Rates of total, ouabain-sensitive and furosemide-sensitive sodium efflux through the lymphocytic cell membrane were measured before thrombolysis, then 3 and 5 days after, using the method elaborated by Haegerty et al. All patients were treated with aspirin, glyceryl trinitrate and thrombolysis therapy with alteplase (r-TPA). In all patients with AMI rates of total and ouabaine-sensitive sodium efflux through the lymphocytic cell membrane were decreased, but rates of furosemide-sensitive sodium efflux were normal. In patients after thrombolytic therapy with reperfusion, 3 and 5 days after thrombolysis the decreased rates were normal, but they were still decreased in patients without reperfusion.
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PMID:[Sodium efflux through lymphocytic cell membranes in patients with acute myocardial infarction]. 1040 67

We have studied extracts from three species rich in lanostane triterpenes for their activity against different in vivo models of inflammation induced by TPA, EPP and PLA(2). The inhibitory effect against PLA(2) in vitro was also studied. When the Poria cocos extract was tested against PLA(2)-induced mouse paw edema, it was active by the oral and parenteral routes. Its effect was greater in both magnitude and duration than that of Pistacia terebinthus and Ganoderma lucidum extracts. P. terebinthus was effective against chronic and acute inflammation, and according to a preliminary chromatographic analysis, its seems to be a good source of lanostane anti-inflammatory agents. G. lucidum was the least effective of the three species studied and, unlike the other two, failed to inhibit the activity of PLA(2) in vitro.
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PMID:On the anti-inflammatory and anti-phospholipase A(2) activity of extracts from lanostane-rich species. 1102 40

Neuropeptide Y (NPY) has been recently characterised as one of the strongest circulating vasoconstrictor peptides, its elevated level may cause coronary artery spasm and increase of peripheral vascular resistance. All this contributes to ischemic myocardial damage and decrease of regional and global left ventricular function. The aim of the study was the examination of NPY plasma levels in patients with acute myocardial infarction (AMI) after thrombolytic therapy with or without reperfusion. The survey was made in 82 patients with AMI after thrombolytic therapy: 40 of them without reperfusion and 42 with reperfusion. The control group consisted of 20 healthy persons. Plasma levels of NPY were measured before thrombolysis, then 1, 3 and 5 days after, using a radioimmunologic method. All patients were treated with aspirin, glyceryl trinitrate and thrombolytic therapy (TT) with alteplase (r-TPA). In patients with AMI, NPY plasma levels were normal before and 1 day after TT, and were significant elevated 3 days after TT 5 days after TT, plasma NPY levels were still high in patients without reperfusion, but they decreased in patients with reperfusion. There was significant negative correlation between NPY level and left ventricular ejection fraction measured 5 days after AMI. During 30-days follow up systolic dysfunction of left ventricle with ejection fraction under 40% occurred in 21 patients and in 11 of them clinical symptoms of heart failure were observed. Using the multivariable regression analysis we showed that NPY concentration over 60 pg/ml is the independent factor leading to left ventricle systolic dysfunction. The results of our study suggest the contribution of NPY to the left ventricular remodeling after AMI.
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PMID:[Plasma levels of neuropeptide Y i patients with current myocardial infarction]. 1150 45

To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.
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PMID:[Blood coagulation changes in patients with post-splenectomy persistent thrombocytosis]. 1158 73


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