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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse teratocarcinoma cells from embryoid bodies were cultured in vitro to permit their differentiation into a number of cell types. Two enzyme activities, creatine phosphokinase (CPK) and the protease plasminogen activator, were studied to follow the developmental sequence of events in these embryoid body-derived cell cultures. CPK activity increased with time in culture, indicating the appearance of new cell types with brain- or muscle-specific enzyme activities. Plasminogen activator was detectable in extracts of embryoid bodies. This protease activity first increased and then decreased to a low level as the embryoid bodies in culture developed into differentiated cell types. These cell cultures also showed a decreased potential for tumor formation in syngeneic mice as a function of time in culture. This decrease in tumorigenic potential was correlated with the appearance of differentiated cells in vitro. Simian virus 40 (SV40) was used to infect and transform cells derived from embryoid bodies in culture. This was done to permit the establishment of cloned teratocarcinoma-derived cell lines. Twenty-nine distinct cloned permanent cell lines (called SVTER) containing the SV40-specific tumor antigen were obtained. None of these cell lines was capable of producing tumors in syngeneic mice. An analysis of the levels of creatine phosphokinase and plasminogen activator in these SVTER cell lines indicated that : (a) some cell lines had high CPK activity and little or no plasminogen activator activity, (b) some cell lines contained high levels of plasminogen activator activity with little or no CPK activity, and (c) some cell lines contained neither of these enzyme activities. No example of a cell line with high levels of both enzyme activities was observed, indicating that these two enzymes may participate in mutually exclusive developmental pathways. The SVTER cell lines may therefore be useful in reconstructing these developmental pathways in vitro.
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PMID:In vitro differentiation of teratomas and the distribution of creatine phosphokinase and plasminogen activator in teratocarcinoma-derived cells. 18 30

Plasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.
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PMID:Von Willebrand factor, plasminogen activator inhibitor-1 and C-reactive protein are markers of thrombolytic efficacy in acute myocardial infarction. 128 82

Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS) 155 7

Ventricular arrhythmias during thrombolysis for acute myocardial infarction and their relation to coronary artery patency were examined. Twenty-four-hour Holter monitoring was begun 3.1 +/- 0.2 hours after onset of pain in 40 patients (age 54 +/- 1.6 years; anterior infarction 42.5%) treated with streptokinase (42.5%) or recombinant tissue-type plasminogen activator (57.5%) (delay from pain 3.3 +/- 0.2 hours). A Marquette 8000 computer was used for Holter analysis. The infarct-related artery was considered as patent (72.5%) or non-patent (27.5%) according to coronary angiography (delay from pain 26.7 +/- 2.5 hours; 60% less than 24 hours). Ventricular arrhythmias were present in all patients. Tolerance was good (1 cardioversion for ventricular fibrillation). The incidence of accelerated idioventricular rhythm was not different between patients with a patent and nonpatent artery (90 vs 82%), nor for ventricular tachycardia (VT) (83 vs 73%). Coronary artery patency was associated with a 14-, 13- and 32-fold increase of ventricular premature complexes, VT and accelerated idioventricular rhythms, respectively. The increased incidence of sustained VT (patent 38%; nonpatent 0%; p less than 0.05) and early (before the first 6 hours) accelerated idioventricular rhythm (patent 76%; nonpatent 18%; p less than 0.01) associated with artery patency suggests that these arrhythmias may be noninvasive diagnostic criteria for reperfusion (sensitivity 38 vs 76%, and specificity 100 vs 82%). A positive correlation was found between the frequency of ventricular premature complexes and VT, and peak creatine kinase.
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PMID:Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction. 173 50

To evaluate the effect of recombinant tissue plasminogen activator (alteplase) on the clinical course, angiographic changes and the outcome of subsequent coronary angioplasty, 36 patients with angina at rest, despite bedrest and medical treatment including heparin, and with concomitant ECG changes, were studied. After diagnostic angiography, patients were randomized to receive either alteplase 100 mg in 3 h (19 patients), or placebo (17 patients). The mean interval between qualifying anginal episode and initial angiography was 10 and 9 h for the alteplase and placebo group, respectively. Angiography was repeated and angioplasty was performed within 24 hours. Between the first and the second angiogram, five patients in the alteplase and seven in the placebo group had recurrent ischaemic episodes, while four alteplase and three placebo patients showed signs of myocardial necrosis (creatine kinase (CK) rise greater than or equal to twice the upper limit for normal). Intracoronary clots were recognized in three alteplase patients and one placebo patient at the first angiogram, while two alteplase patients and one placebo patient showed total occlusion of the ischaemic-related vessel. After infusion, thrombi were present in four alteplase patients and one placebo patient, and total occlusion in three alteplase patients and one placebo patient. Quantitative coronary angiography showed no change in the percentage diameter stenosis of the ischaemia-related segment after drug infusion, (alteplase 67 +/- 16 to 69 +/- 16%; placebo 65 +/- 11 to 63 +/- 12%). Angioplasty was successful in 14 of 19 alteplase and 14 of 16 placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue plasminogen activator in refractory unstable angina. A randomized double-blind placebo-controlled trial in patients with refractory unstable angina and subsequent angioplasty. 178 51

Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change.
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PMID:Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. 189 76

Alteplase (recombinant tissue-type plasminogen activator (rt-PA)) was infused within four hours of onset of symptoms in 286 patients with acute myocardial infarction. Delayed coronary angiography was performed 72 hours after admission with coronary angioplasty if indicated. Electrocardiographic monitoring was continuous during the first hour of treatment. The sum of the ST segment elevations (sigma ST) was calculated on electrocardiograms recorded at entry and an hour later. ST elevations resolved rapidly within one hour of treatment in 189 patients and persisted in 97 patients. Rapid resolution of ST elevation correlated with angiographic coronary patency as determined by coronary angiography 72 hours after admission. The patients with rapid resolution of sigma ST had significantly smaller infarcts and a better clinical outcome than the patients with persistent ST elevation. sigma ST values at entry and one hour after treatment had no additional independent predictive value. Rapid resolution of ST elevations in patients undergoing thrombolysis with alteplase was associated with a significantly smaller release of creatine kinase, better preservation of left ventricular function, lower morbidity, and less short and long term mortality. Rapid resolution of sigma ST elevation is an efficient indicator of clinical outcome in groups of patients with acute myocardial infarction undergoing thrombolysis with alteplase.
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PMID:Rapid resolution of ST elevation and prediction of clinical outcome in patients undergoing thrombolysis with alteplase (recombinant tissue-type plasminogen activator): results of the Israeli Study of Early Intervention in Myocardial Infarction. 212 Nov 99

The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.
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PMID:Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction. 212 6

Fibrinopeptide A (FPA) is a very sensitive marker of fibrin generation in vivo. Because an imbalance between thrombogenic and thrombolytic forces may be responsible for the failure to recanalize and for reocclusion of coronary arteries, such a marker could be of eminent value during thrombolytic treatment of acute myocardial infarction. Thirty-four consecutive patients with acute myocardial infarction (peak creatine kinase level, 1,869 +/- 1,543 IU/l) were treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) 3.1 +/- 1.1 hours after onset of chest pain. Angiography 12.5 +/- 6.1 days later revealed an 81% patency rate of the infarct-related vessel. FPA plasma levels (normal, 1.9 +/- 0.5 ng/ml) were 34 +/- 46 ng/ml on admission and 93 +/- 86 ng/ml (538 +/- 674% with respect to each patient's admission level) after 90 minutes of rt-PA infusion (p less than 0.01). In patients without evidence of reocclusion (including three primary failures), FPA levels fell under continuous heparin infusion to 6.7 +/- 9.7 ng/ml (24 +/- 33%, p less than 0.01) within 30 minutes and were 3.1 +/- 2.2 ng/ml (15 +/- 15%, p less than 0.01), 1.6 +/- 1.1 ng/ml (8 +/- 10%, p less than 0.01), and 2.5 +/- 3.0 ng/ml (12 +/- 16%, p less than 0.01) 30 minutes, 9 hours, and 21 hours, respectively, after completion of rt-PA therapy. Five patients sustained intermittent or permanent coronary reocclusion after primary thrombolytic success. Their early postlytic FPA levels (13-51 ng/ml) remained high or increased again despite adequate anticoagulation. FPA allows the monitoring of fibrin generation during acute myocardial infarction and thrombolytic therapy. Despite successful recanalization, fibrin generation is increased under rt-PA administration before anticoagulation. Patients under anticoagulation with postlytic FPA levels less than 5 ng/ml or below their admission value seem to be at low risk of reocclusion for several days. FPA levels that are persistently high or that increase again despite adequate anticoagulation indicate ongoing fibrin generation. However, whether FPA can indeed be considered a useful marker of reocclusion remains to be confirmed in a larger population of patients with acute myocardial infarction.
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PMID:Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator. 249 39

To determine the role of tissue-type plasminogen activator (t-PA) and immediate percutaneous transluminal coronary angioplasty (PTCA) in treating patients with evolving transmural myocardial infarction, 50 patients received t-PA (1.25 mg/kg iv over 3 hrs) or placebo according to 3:1 double-blind randomization 3.8 +/- 1.1 hr after onset of symptoms. At emergency coronary arteriography, patency of the infarct-related vessel was demonstrated in 32 of 38 (84%) patients receiving t-PA vs two of 12 (17%) receiving placebo (p less than .001). Of the 32 patients with recanalization after t-PA, 28 had a residual stenosis of at least 50% and underwent randomization a second time to immediate (n = 15) or no PTCA (n = 13). Immediate PTCA of the infarct-related vessel was successful in all 15 patients, with reduction of the residual diameter stenosis from 80.8 +/- 8.2% to 32.5 +/- 15.6% (p less than .001). The incidence of postinfarction angina (greater than or equal to 20 min of chest discomfort and reversible electrocardiographic changes) and reinfarction (documented by recurrent creatine kinase isoenzyme elevation) was reduced in the patients receiving t-PA and PTCA (2/15) compared with that in patients receiving t-PA alone (7/13; p = .006). At 1 week there was no difference in patency of the infarct-related vessel (12/15 t-PA and PTCA vs 9/13 t-PA only) or in global ventricular functional change between the two groups (0.5 +/- 10.4 SD/chord for t-PA and PTCA vs -2.1 +/- 8.2 SD/chord for t-PA only).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator and emergency coronary angioplasty in patients with acute myocardial infarction. 294 35


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