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)

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator. 250 11

In the present study the possible dual effects of adenosine as substrate and adenosine receptor agonist in rat granulosa cells, cumulus-oocyte complexes, luteal cells and ovarian membranes are discussed. Adenosine is an indispensable compound in cell energy metabolism, as precursor to cofactors, second messenger and nucleic acids. Adenosine is also an agonist to adenosine receptors. The adenosine receptor can either inhibit (A1) or stimulate (A2) adenylate cyclase. Alternatively, in some cells adenosine receptor activation is linked to other cellular events like inhibition of Ca2+ fluxes. Adenosine is taken up by isolated preovulatory granulosa and luteal cells from pregnant mare serum gonadotropin-treated immature rats, but follicle stimulating hormone (FSH) decreases the uptake by granulosa cells. Adenosine, but not the non-metabolizable adenosine analogs 5'-(N-ethyl)carboxamide-adenosine (NECA), 2-chloro-adenosine (2-Clado), N6-(R-phenyl-isopropyl)-adenosine (R-PLA) and N6-(S-phenyl-isopropyl)-adenosine (S-PLA), increase granulosa cell ATP levels. FSH and luteinizing hormone (LH) decrease granulosa cell ATP levels in the presence or absence of adenosine. It has previously been shown that FSH and LH decrease oxygen consumption by cumulus-oocyte complexes and increase their lactate production. These effects have been suggested to be due to a competition of cofactors (e.g. ADP) common to glycolysis and the respiratory chain. The fact that adenosine reverse the gonadotropin-induced effects on oxygen consumption and lactate production support this theory. Adenosine and its analogs increase cAMP accumulation in luteal and granulosa cells only in the presence of gonadotropins, and this effect is antagonized by the adenosine receptor antagonist 8-phenyl-theophylline (8-PHT). Furthermore, adenylate cyclase is stimulated by adenosine analogs in membranes from non-luteinized and luteinized ovarian membranes and in luteal cell homogenates. The effect of NECA is antagonized by 8-PHT. In the membranes, the rank order of potency was NECA greater than 2-Clado greater than R-PLA greater than S-PLA, suggesting adenosine A2 receptors. In summary, it is suggested that adenosine can act both as a substrate to intracellular metabolism and as an adenosine A2 receptor agonist in granulosa and luteal cells. A paracrine short loop positive feedback model is proposed where extracellular adenosine, derived from a gonadotropin-induced extracellular increase in cAMP and a decrease in cellular ATP, enhances gonadotropin stimulation in granulosa and luteal cells.
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PMID:Adenosine as substrate and receptor agonist in the ovary. 255

Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce greater than 90% stenosis (reducing blood flow to 40 +/- 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 micrograms/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 +/- 7 min (mean +/- SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 +/- 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P less than 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA.
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PMID:Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs. 283 48

To investigate the effect of moderate alcohol consumption on blood constituents related to cardiovascular disease, 12 male volunteers consumed (instead of their usual alcoholic drinks) four different standardized amounts of red wine in addition to their habitual diet. Each dose was given to the subjects during a period of 5 weeks in a randomized order, all subjects receiving the four doses. They consisted of 0, 2, and 4 glasses/d, providing 0, 23, and 46 g alcohol/d as well as in "binge drinking" (14 glasses in the weekend, comparable to an average of 2 glasses/d). The results showed a clear dose-related response to the drinking for several blood constituents. Most marked was a decrease in the tissue-type plasminogen activator activity and to a lesser degree an increase in plasminogen levels. Collagen-induced platelet aggregation was reduced, affecting all parameters measured. Levels of HDL3-cholesterol, gammaglutamyltransferase, and urate showed a small but significant increase. No change was noted in the levels of alkaline phosphatase, alanine-aminotransferase, aspartate-aminotransferase, bile acids, folate, fibrinogen, the ADP-induced platelet aggregation, platelet secretion, or in hematologic values. The results are only partially in accordance with the presumed protective action of moderate drinking on the cardiovascular system and show a stronger response to the consumption of alcohol in coagulation and fibrinolysis factors than in blood lipids.
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PMID:Effects of moderate alcohol consumption on platelet aggregation, fibrinolysis, and blood lipids. 288 51

The relative contribution of platelets to plasminogen activator inhibitor (PA-inhibitor) activity in blood was investigated. From the difference in PA-inhibitor levels in platelet-poor plasmas of 12 donors (3 +/- 1 U/ml, mean +/- 95% confidence limits) and in the corresponding platelet-rich plasmas after induction of platelet aggregation by collagen, ADP or epinephrine (7 +/- 1 U/ml), it may be concluded that a greater amount of PA-inhibitor in blood is associated with platelets than with plasma. In collagen-stimulated platelets maximal release of PA-inhibitor and of beta-thromboglobulin (beta-TG) was attained within fifteen seconds, whereas in ADP-stimulated platelets the release of both factors was slower. In platelet-poor plasma no correlation was found between the level of PA-inhibitor and that of beta-TG. Thus, the PA-inhibitor found in plasma is not derived from platelets that had been stimulated after blood collection. The rate of complex formation and the Mr of the principal complexes of radioiodinated tissue-type plasminogen activator (t-PA) or urokinase (UK), in platelet-poor plasma, in platelet-rich plasma after platelet aggregation or in an extract of washed platelets was the same. Moreover, complexes of UK or t-PA with plasmatic PA-inhibitor or with the PA-inhibitor(s) from platelets bound to immobilized antibodies against bovine endothelial cell-derived PA-inhibitor. These results show that the PA-inhibitors in plasma and in platelets are very similar or identical.
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PMID:Studies on the release of a plasminogen activator inhibitor by human platelets. 294 Jul 23

The ex vivo aggregability of rabbit platelets was assessed after rabbits were treated in vivo with thrombolytic doses of tissue plasminogen activator (t-PA) or streptokinase (SK). t-PA was evaluated at 2 doses; an effective thrombolytic dose of 10 micrograms/kg/min, i.v. and a higher dose of 30 micrograms/kg/min, i.v.. At both concentrations, ex vivo platelet hyperaggregability was observed when collagen, arachidonic acid or ADP were employed as the aggregating agonists. Significant falls in circulating platelet counts were observed after t-PA infusion. Infusion of SK also resulted in ex vivo platelet hyperaggregation. These data reveal that thrombolytic therapy may result in hyperaggregable platelets which may play a role in reocclusion of successfully recanalized blood vessels.
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PMID:Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. 311 93

The effect of Norplant subdermal implants on 22 different hemostatic variables was determined in 100 women attending the Fertility Control Clinic of the Singapore National University Hospital before and after 6 and 12 months of use. The factors analyzed were: hematocrit, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, fibrinogen, coagulation factor II, Factor V,Factor VII, Factor VIII, Factor VIIIR:Ag, Factor X, plasminogen activator, FDP, plasminogen (imm), antithrombin III (functional), antithrombin (antigen), protein C, alpha2-antiplasmin, alpha2-macroglobulin, alpha2-antitrypsin, platelet count, platelet aggregation (ADP), and platelet aggregation (collagen). The factors that differed significantly after 12 months were: Hb,PT,APTT, Factors II,V,VII, and VIIIR:Ag, Plasminogen (imm), antithrombin III(antigen), alpha2-antiplasmin, platelet count, and platelet aggregation. Most of these differences, while significant, were still within the normal range, except for PT,APTT, and platelet count. The subjects were considered to be in an enhanced risk for hypercoagulation and thrombosis.
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PMID:The effects of Norplant-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. 314 69

DNA repair is an important mechanism of chemotherapy resistance in common human tumours. The normal tissues tolerate the drugs also, hence elucidation of normal pathways, rather than markedly resistant mutants, is more likely to be relevant. Specific repair mechanisms may deal with certain lesions (eg O6-methylguanine) but other more general mechanisms (excision repair, poly ADP ribose) can handle a wide range of lesions. The response of human cells to DNA damage is more complex than simply removing lesions. Interactions with growth factors, induction of receptors for growth factors, production of soluble mediators and secretion of plasminogen activator are parts of a cellular and tissue response. These processes may be more active in earlier, less differentiated cells which are more resistant to radiotherapy and chemotherapy. The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways.
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PMID:DNA repair and resistance to chemotherapy. 391 57

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
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PMID:Release of plasminogen activator from isolated perfused dog heart. 403 71

There is an increased frequency of arterial thrombosis in cigarette smokers. The changes in blood coagulation seen in these subjects have been studied by many workers but results have not always been in agreement. We wished to study the effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in ten habitual smokers, and to compare these results with non-smoking controls. Results show that the smoking group had higher plasma fibrinogen (p less than 0.04), lower plasminogen (p less than 0.02) and plasminogen activator (p less than 0.05), and higher plasma viscosity (p less than 0.003). The changes seen in cigarette smokers after smoking three cigarettes were an increase in the rate of platelet aggregation to ADP (p less than 0.02), an increase in alpha 2M, (p less than 0.02), and factor VIII RAG (p less than 0.05). Plasma viscosity was decreased (p less than 0.02) as was red cell deformability (p less than 0.02). We confirm an increased tendency to hypercoagulability in smokers compared to controls which becomes more pronounced immediately after smoking three cigarettes.
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PMID:The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers. 623 29


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