Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We had rare opportunities to examine changes in fibrin degradation products (FDP)-D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and other coagulation parameters during the clinical courses of living-related partial liver transplantation (LRPLT). In seven out of eight recipients without severe rejection and/or disseminated intravascular coagulation (DIC), FDP-DD values reached their maximum at 5 to 10 days after transplantation, then gradually decreased. On the other hand, TAT values rose to the maximum at anhepatic or reperfusion phase of liver transplantation. These data represent hypercoagulation in consequence of tissue thromboplastin activation after extensive operation. Changes in PIC, tissue-type plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) in the clinical course of case 1 suggested that fibrinolysis was suppressed by relatively elevated level of PAI-1 around the operation, but thereafter was adversely accelerated by relatively lower levels of PAI-1. In comparison with patients with DIC, TAT was much higher but PIC was significantly lower in recipients of LRPLT. These findings indicated that marked hypercoagulation and mild to moderate hyperfibrinolysis occurred in recipients of LRPLT.
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PMID:[Changes in coagulation parameters during the clinical courses of recipients of living-related partial liver transplantation]. 747 43

Levels of tissue plasminogen activator antigen (t-PA:ag), tissue plasminogen activator inhibitor 1 antigen (PAI-1:ag) and tissue plasminogen activator inhibitor activity (PAI activity), and alpha-2-antiplasmin (AAP) were measured in plasma from 19 patients with severe trauma on admission and on days 1, 2, 3 and 7 after the incident. In all patients the Injury Severity Score (ISS) and the number of blood transfusions were recorded. The development of post-traumatic pulmonary dysfunction was observed in four patients. Levels of t-PA:ag, PAI-1:ag and PAI activity were increased, and levels of AAP were low immediately after trauma. Levels of t-PA:ag normalized during the first week, whereas PAI-1:ag levels decreased gradually from day 1 to day 3. Thereafter a secondary increase was observed. A similar trend was observed in levels of PAI activity. Levels of APP increased significantly during the first week. t-PA:ag, PAI-1:ag or PAI activity levels were not correlated with the ISS on any day, but levels of AAP showed a weak correlation with the ISS on day 7. Post-traumatic levels of t-PA:ag and PAI-1:ag were higher in patients who had 6 or more units of blood transfusions for resuscitation. The fibrinolytic markers were not significantly different in patients who had pulmonary dysfunction compared with patients without.
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PMID:Levels of fibrinolytic activators and inhibitors in plasma after severe trauma. 751 44

We compared the thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA; del 92-173, 275Arg-->Glu), YM866, with that of t-PA in a platelet-rich thrombosis model. Thrombus was induced in guinea pig mesenteric artery by irradiation with filtered light in combination with intravenous (i.v.) administration of fluorescent dye. When occlusion by the thrombus extended to 99% of the luminal area of the vessel, test drug (YM866, t-PA, or saline) was administered by i.v. bolus injection under heparinization. Both YM866 and t-PA exhibited dose-dependent thrombolytic activity; however, the improvement in occlusion rate and the incidence of successful thrombolysis induced by YM866 were three times higher than those induced by t-PA. With YM866 1 mg/kg, alpha 2-plasmin inhibitor levels decreased significantly to 58% of saline group values, but no change was noted in fibrinogen levels. YM866 antigen levels at this dose were seven times higher than those of t-PA. These results suggest that YM866 in single bolus injection is a thrombolytic agent superior to t-PA in platelet-rich thrombi without systemic fibrinolytic activation and that this efficacy is due to the prolonged half-life (t1/2) of the drug.
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PMID:Thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, in a photochemically induced platelet-rich thrombosis model. 752 79

The main cause of nonsurgical bleeding during orthotopic liver transplantation has been attributed to be hyperfibrinolysis due to high plasma levels of tissue plasminogen activator. The aim of this study was to investigate contact activation and its possible contribution to fibrinolysis during OLT with and without aprotinin. Aprotinin or placebo was given to 20 patients undergoing OLT as part of a randomized double-blind trial. Plasma samples were collected before, during, and after OLT. There were decreased preoperative levels of prekallikrein and factor XIIa (P < 0.05), with a trend for kallikrein and factor XIIa activity to increase during OLT peaking on reperfusion (P < 0.05). Kallikrein inhibition, C1 esterase inhibitor, and alpha-2-macroglobulin levels were normal before surgery, with low normal levels of antithrombin III and alpha-2-antiplasmin; these levels decreased during OLT with no specific change on reperfusion. In the aprotinin-treated group, kallikrein inhibition levels increased (P < 0.05) from preoperative mean (+/- SD) values of 101 +/- 47% to 154 +/- 42% and antiplasmin levels increased (P < 0.05) from 72 +/- 28% to 243 +/- 53% during the anhepatic phase, reflecting the effect of aprotinin. The antifibrinolytic effect of aprotinin was demonstrated by decreased levels of D-dimer on reperfusion (P < 0.05) and at the end of OLT (P < 0.001) in the aprotinin-treated group. We have shown that contact activation during OLT is minimal and that aprotinin does not alter the pattern of contact activation, but provides an antikallikrein effect.
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PMID:Changes in the contact system during orthotopic liver transplantation with and without aprotinin. 753 78

We examined the role of the plasminogen activator/plasmin system in extracellular matrix (ECM) degradation by human mesangial cells cultured on thin films of 125I-labeled ECM (Matrigel). ECM degradation (release of 125I into the medium) was dependent on exogenous plasminogen, proportional to the number of mesangial cells and amount of plasminogen added, and coincident with the appearance of plasmin in the medium. ECM degradation was completely blocked (P < 0.001) by two plasmin inhibitors, alpha-2-antiplasmin (40 micrograms/ml) and aprotinin (216 KIU/ml), and partially reduced (-33 +/- 1.8%, P < 0.01) by TIMP-1 (40 micrograms/ml), a specific inhibitor of matrix metalloproteinases. Zymography of medium obtained from cells cultured in the absence of plasminogen revealed the presence of latent matrix metalloproteinase-2 (MMP-2) which was converted to a lower molecular weight, active form in the presence of mesangial cells and plasminogen. Northern analysis of poly A+RNA prepared from cultured human mesangial cells revealed mRNA for tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA receptor (uPAR). The presence of uPA protein in medium obtained from cultured human mesangial cells was demonstrated by Western blotting and ELISA which revealed a large molar excess of PAI-1 (1.2 +/- 0.1 x 10(-9) M) over uPA (1.2 +/- 0.1 x 10(-12) M) and tPA (0.19 +/- 0.04 x 10(-9) M). ECM degradation was reduced by a monoclonal antibody (MAb) against human tPA (-54 +/- 8.6%) or human uPA (-39 +/- 5.2%) compared to cells treated with identical amounts of non-specific monoclonal IgG (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ECM degradation by cultured human mesangial cells is mediated by a PA/plasmin/MMP-2 cascade. 754 Feb 30

It has been reported that plasma fibrinolytic activity is abnormal in some patients with chronic low back pain. In an attempt to confirm this finding we studied 22 patients with chronic mechanical low back pain and compared them with 18 healthy controls who denied symptoms of back pain. Factors known to interfere with plasma fibrinolysis such as age, weight, seasonal and diurnal variation, exercise, smoking and drugs were controlled as far as possible. Plasma fibrinogen was significantly higher (2.8 versus 2.3 g/l, P < 0.005) in patients than in controls, but there were no significant differences in the median plasma concentrations of euglobulin clot lysis time, fibrin plate lysis area, plasminogen, alpha-2-antiplasmin, tissue plasminogen activator activity, and antigen, tissue plasminogen activator inhibition and plasminogen activator inhibitor-1 antigen level. The results fail to confirm abnormalities of plasma fibrinolytic activity in a group of unselected cases of chronic low back pain.
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PMID:Lack of evidence for abnormal fibrinolysis in chronic low back pain. 836 4

To evaluate the effects of lipoprotein (a) [Lp (a)] on the fibrinolytic system in patients with acute myocardial infarction (AMI) who underwent thrombolytic therapy with recombinant tissue-type plasminogen activator, we examined serial changes in plasma levels of Lp (a), plasminogen activator inhibitor (PAI) activity, alpha 2-plasmin inhibitor-plasmin complex (PIC) and thrombin antithrombin III complex (TAT) in venous plasma samples from 25 patients with AMI for 3 weeks. Plasma Lp (a) levels were significantly increased 5, 7, and 14 days after admission and tended to decrease by the 21st day. On the other hand, the ratio of PIC/TAT was significantly increased on the 7th day and remained high for 3 weeks (p < 0.01), while plasma PAI activity was significantly decreased on the 5th day after admission (p < 0.01). Thus, plasma fibrinolytic function is impaired in the early phase after AMI, and gradually improves over the course of 3 weeks. The increase in plasma Lp (a) levels is, therefore, not accompanied by a significant decrease in plasma fibrinolytic function in patients with AMI.
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PMID:Plasma lipoprotein (a) levels and fibrinolytic activity in acute myocardial infarction. 769 33

We compared the fibrinolytic properties of recombinant staphylokinase (SAK), a fibrin-specific plasminogen activator, with those of streptokinase and tissue-type plasminogen activator (t-PA) by means of the amidolytic method. We also investigated the involvement of alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin in SAK-induced fibrin-specific fibrinolysis. Both SAK and t-PA activated plasminogen efficiently in the presence of fibrin in human plasma. Although t-PA activated plasminogen dependently on fibrin in the reconstituted plasma system, SAK activated plasminogen independently of fibrin without alpha 2-plasmin inhibitor (alpha 2-antiplasmin, alpha 2-PI). These findings suggest that fibrin and alpha 2-PI play important roles in plasminogen activation by SAK but not by t-PA. Furthermore, protease inhibitors such as alpha 2-PI, alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin inhibited plasminogen activation by SAK and the inhibitory actions of these protease inhibitors disappeared in the presence of fibrin. This shows that alpha 2-macroglobulin, C1-inactivator and alpha 1-antitrypsin, other than alpha 2-PI, contribute to the fibrin-specificity of SAK.
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PMID:Involvement of protease inhibitors in staphylokinase-induced fibrin-specific fibrinolysis. 773 1

Methods for measuring antigen and activity of plasminogen activators (t-PA, u-PA), plasminogen activator inhibitors (PAI-1, PAI-2) and their complex have been improved in the past few years, but few comparative data are available and they should be standardized. In particular the commercial kits for determination of PAI-1 activity seem to be not accurate for the measurement of PAI-1 in plasma. The amount of generated plasmin can be measured as plasmin-alpha-2-antiplasmin complex (PAP). There are also some new tests which could differentiate between fibrinogenolysis (FgDP) and fibrinolysis (FnDP, D-dimer) as between primary and secondary activation of fibrinolysis (B beta 15-42 peptide). Normal D-dimer plasma concentration allows for the ruling out of venous thromboembolism with high probability, but the specificity of this tests is poor.
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PMID:[Progress in the detection of intravascular activation of fibrinolysis]. 774 60

An examination was made of the coronary thrombolytic effects of nasaruplase in a canine model of acute myocardial infarction. The model was produced by selective injection of an artificial thrombus into the coronary artery stenosed by laser ablation. Intravenous nasaruplase (8 U/kg/min) showed an equivalent thrombolytic effect to a recombinant tissue-type plasminogen activator (rt-PA, 10,000 IU/kg/min) as assessed by reperfusion rate (78.6 versus 79.2%) and reperfusion time (37.4 +/- 5.2 versus 37.0 +/- 2.5 min). Nasaruplase decreased the plasma alpha 2-plasmin inhibitor (alpha 2-PI) level by 28% immediately after reperfusion, but hardly altered fibrinogen or plasmin-alpha 2-plasmin inhibitor complex (PIC) levels. By contrast, rt-PA significantly decreased plasma alpha 2-PI and fibrinogen levels, by 84% and 92% respectively, and, increased PIC level more than 70-fold. Hemorrhagic infarction occurred in 2 of 14 animals in the nasaruplase group and in 9 of 19 animals in the rt-PA group. In these animals, significant correlations were found between the ratio of the hemorrhagic infarction area to total infarct area and the plasma alpha 2-PI (r = -0.740, p < 0.05) or fibrinogen (r = -0.798, p < 0.05) concentrations, as well as between the recovery rate of left ventricular regional wall motion and the plasma alpha 2-PI (r = 0.924, p < 0.01) or fibrinogen (r = 0.864, p < 0.01) concentrations. It is concluded that nasaruplase is a potent thrombolytic agent which preserves left ventricular function with a lesser rate of hemorrhagic infarction than rt-PA. Further, nasaruplase administration results in recovery of left ventricular regional wall motion and systolic function, such as Vmax.
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PMID:Low incidence of hemorrhagic infarction following coronary reperfusion with nasaruplase in a canine model of acute myocardial infarction. Comparison with recombinant t-PA. 776 May 15


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