Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study on the clinical effects of urokinase in patients with IgA nephropathy is described. Three different methods of administration, including single, continuous, and mixed administration, were employed in this study. Measurements of plasminogen, plasmin and alpha 2-plasmin inhibitor levels in plasma were performed during the course of urokinase administration in patients with IgA nephropathy and chronic proliferative glomerulonephritis. Measurements of alpha 1-anti-trypsin and alpha 2-macroglobulin levels were also performed in these patients. Urinalysis was performed both before and after administration of urokinase. It was demonstrated that a single shot of urokinase induced a significant fibrinolytic activity in patients with IgA nephropathy, and that a single shot of urokinase was effective in improving proteinuria and/or hematuria in patients with IgA nephropathy. It is concluded that a single shot of urokinase may be useful for treatment of patients with IgA nephropathy.
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PMID:Effects of a "single shot" of urokinase on fibrinolytic activities in patients with IgA nephropathy. 653 1

Coagulation and fibrinolytic factors in the blood were measured during heparin-urokinase (UK)-pulse combined therapy in order to investigate the background for the availability of the therapy. Five patients with nephritis resistant to conventional treatment were treated with this combined therapy (heparin: 350-450 U/kg day, continuously i.v. during the therapy; UK: 5000 IU/kg/2 hrs, i.v., two times a day, for 3 days = 1 Kur; methylprednisolone 20 mg/kg/2hrs, d.i.v., for 3 days = 1 Kur; 3 Kurs of UK and 3 Kurs of pulse were alternately administered). 1) Blood levels of alpha 2-plasmin inhibitor (alpha 2-PI) antigen were decreased and those of alpha 2-plasmin inhibitor.plasmin complex (alpha 2-PI. PmC) were elevated during 3 Kurs of UK administration. Accordingly, activation of the fibrinolytic system was confirmed during the combined therapy, suggesting that both alpha 2-PI and alpha 2-PI.PmC were relevant in monitoring the fibrinolytic state in blood. 2) Both tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were sustained continuously in the elevated levels in the blood during both UK administration and pulse therapy. This movement of t-PA and PAI-1 was independent of that of the other fibrinolytic factors, such as alpha 2-PI,alpha 2-PI.PmC and plasminogen. 3) Inflammatory reactants such as fibrinogen, alpha 2-PI,alpha 2-macroglobulin and alpha 1-antitrypsin decreased more significantly during this heparin-urokinase-pulse combined therapy than during our previous combined therapy consisting of only heparin and urokinase. Therefore, we conclude that the anti-inflammatory effect was reinforced by adding the pulse therapy and that the combined therapy had some effect on the release of t-PA from vascular endothelial cells.
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PMID:[Changes in coagulation and fibrinolytic factors observed during heparin-urokinase-pulse combined therapy for nephritis resistant to conventional treatment in children]. 750 45

Using plasminogen-Sepharose 4B chromatography, a 50-70% reduction in the alpha-2-antiplasmin (alpha-2-AP) content in human and dog blood plasma was reached. The decrease in the alpha-2-AP concentration in human and dog blood plasma markedly enhanced the lysis of fibrin clots formed from the plasma under the action of urokinase and streptokinase. Thus, the lysis of model clots for a definite period of time for human and dog blood plasma depleted for alpha-2-AP by 50-70% required 5-8 and 3-6 times as low urokinase and streptokinase concentrations as those needed for the clot lysis in the native plasma. The decrease in the fibrinogen concentration in human blood plasma caused by plasmosorption on plasminogen-Sepharose enhanced the model fibrin clot lysis by urokinase and streptokinase, however, by no more than 5-10%. Hence, the increased efficiency of plasminogen activators in the given model system can be accounted for by the decline of the antiplasmin potential of the blood plasma.
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PMID:[Intensification of the effect of exogenous plasminogen activators on lysis of fibrin blood clots due to a decrease in the level of alpha-2- antiplasmin by a plasmasorption method]. 750 43

The aim of the present study was to display plasminogen/plasmin receptors on human glomerular epithelial cell (HGEC) membranes and to determine the properties of receptor-bound plasminogen at the cell surface. Using an immortalized human glomerular epithelial cell line (E71-A1), we found a specific, saturable, and reversible binding of 125I-labeled plasminogen and 125I-labeled plasmin to HGEC that involved the lysine binding sites of both ligands. 125I-plasminogen and 125I-plasmin bound to the same receptors with different affinities: Kd = 1.20 +/- 0.08 and 0.30 +/- 0.05 microM, respectively (P < 0.001). The number of binding sites per cell was 6.00 +/- 0.56 x 10(6) for plasminogen and 2.00 +/- 0.47 x 10(6) for plasmin (P < 0.05). Similar receptor affinities were found on isolated glomeruli, on immortalized and nonimmortalized HGEC, and on purified HGEC membranes. The apparent kinetic constants of plasminogen activation by receptor-bound urokinase-type plasminogen activator (u-PA) compared with solution-phase u-PA [Michaelis constant (Km) = 0.80 +/- 0.54 vs. 3.15 +/- 0.78 microM, P < 0.0001; catalytic constant (kcat) = 0.39 +/- 0.17 vs. 0.50 +/- 0.29 s-1, not significant; kcat/Km = 0.57 +/- 0.35 vs. 0.16 +/- 0.11 microM-1.s-1, P < 0.05, respectively] showed a higher efficiency of plasminogen activation at the cell surface. When measured by a chromogenic assay using S22-51, receptor-bound plasmin activity on HGEC was partly protected from its inhibitor, alpha-2-antiplasmin, whereas solution-phase plasmin was not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of plasminogen/plasmin receptors on human glomerular epithelial cells. 752 Jun 69

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

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

Intracerebral hemorrhagic transformation is one of the most important complications of thrombolytic therapy for acute ischemic stroke. The relationship between changes in markers for the coagulation and fibrinolytic systems and occurrence of hemorrhagic transformation was determined after local intra-arterial thrombolytic therapy using urokinase (UK) (24 patients) or recombinant tissue plasminogen activator (t-PA) (10 patients) within 6 hours of onset. All 34 patients had no hypodensity areas on initial computed tomography scans. Plasma concentrations of fibrinogen-fibrin degradation products (FDP), fibrinogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2 plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and D-dimer were measured. Hemorrhagic transformation occurred in seven patients (21%) with complete or partial recanalization; four in the UK group and three in the t-PA group. Doses of the thrombolytic agents did not correlate with the incidence of hemorrhagic transformation. The FDP levels in the hemorrhagic transformation group treated with UK significantly increased immediately and 1 hour after the therapy. The alpha 2-PI activities decreased and PIC levels increased in both the hemorrhagic transformation and the nonhemorrhagic groups after the therapy. The TAT levels in both groups tended to be higher than the normal range, but there was no significant difference from the pretreatment levels. The D-dimer levels in the hemorrhagic transformation group were higher than those in the nonhemorrhagic group at 24 hours after the therapy. Furthermore, the D-dimer levels were significantly higher in patients with complete recanalization compared with those with none or partial recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in coagulation and fibrinolytic system after local intra-arterial thrombolysis for acute ischemic stroke. 777 Jan 6

Fully activable recombinant human plasminogen (rPlg) was expressed in mammalian cells employing either recombinant vaccinia virus or stable lines coexpressing alpha 2-plasmin inhibitor. A panel of eight variants of rPlg was constructed, in which progressively up to 6 basic amino acid residues in the hinge region of rPlg between the NH2-terminal acidic domain ("proactivation peptide") and kringle 1 were substituted by neutral residues. Analysis of the cleavage rates of these variants by plasmin revealed that the peptide bond at Arg68 is most susceptible, followed by Lys62 and Lys77. A variant with all 6 basic residues substituted was cleaved at Lys20. Three of these variants, PlgB (R68A, R70A), PlgF (R68A, R70A, K77H, K78H), and PlgG (R61A, K62A, R68A, R70A, K77H, K78H), as well as rPlg, were analyzed in more detail. The conformation of these plasminogens was analyzed by monitoring the change in intrinsic fluorescence upon binding of lysine analogs. This revealed that rPlg exhibits the native tight Glu1-plasminogen conformation, whereas PlgB, PlgF, and Plg G display an open conformation similar to Lys78-plasminogen, leading to an increased affinity for lysine analogs. This allowed a direct study of the impact of the activation-resistant conformation on the properties of Glu1-plasminogen. The open conformation of rPlg variants leads to an increased rate of activation by urokinase-type plasminogen activator and streptokinase and increased binding to a fibrin clot. Fibrin clot lysis mediated by tissue-type plasminogen activator was accelerated for the variants as a result of a lower Km for tissue-type plasminogen activator-mediated plasminogen activation, resulting from the increased affinity of rPlg (variants) for intact fibrin. We conclude that the basic residues in the extremely plasmin susceptible hinge region of plasminogen are directly involved in maintaining the activation resistant Glu1-plasminogen conformation.
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PMID:The activation-resistant conformation of recombinant human plasminogen is stabilized by basic residues in the amino-terminal hinge region. 779 79

We compared the thrombolytic properties of recombinant staphylokinase (SAK) with those of streptokinase (SK), a tissue-type plasminogen activator (t-PA) and a urokinase-type plasminogen activator (u-PA) in the jugular vein thrombosis model in the rabbit in vivo and a circulating human plasma system in vitro. 50% thrombolysis was observed at 360 min after intravenous infusion into rabbits of 150 micrograms/kg of SAK or 500 micrograms/kg of t-PA, respectively. And the fibrinogen level in the blood was not affected by either agent. 50% clot lysis in vitro was observed at 120 min with 1.8 micrograms/ml of SAK, 22.1 micrograms/ml of SK, 2.1 micrograms/ml of t-PA, or 4.7 micrograms/ml of u-PA, respectively. All the plasminogen activators with the exception of SAK decreased the residual fibrinogen level in the circulating plasma at their moderate concentration for clot lysis. SAK had less influence on the plasminogen and alpha 2-plasmin inhibitor (alpha 2-antiplasmin) levels than the other plasminogen activators. These findings suggest that SAK is a potent fibrin-specific thrombolytic agent.
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PMID:Fibrin-specific fibrinolysis induced by recombinant staphylokinase. 782 Jan 8

The effects of coronary thrombolytic therapy with urokinase on the intrinsic hemostatic and fibrinolytic states were investigated by determining several markers for hemostatic and fibrinolytic activities in 6 patients with acute myocardial infarction who underwent coronary thrombolysis with urokinase. The markers for hemostasis and fibrinolysis were: markers for plasmin generation [alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, plasmin alpha 2-PI complex (PIC)]; markers for fibrinolysis [fibrin/fibrinogen degradation products-E fragment (FDP-E), FDP D-D dimer (D dimer), fibrinogen]; markers for hemostatic activity (prothrombin time (PT), antithrombin III (AT-III), protein C); markers for thrombin generation [thrombin antithrombin III complex (TAT)]; markers for intrinsic fibrinolytic activity [tissue plasminogen activator plasminogen activator inhibitor complex (TPA PAI complex)]. These markers were measured before, at 1 to 2 hours intervals during first 6 hours, daily during the next 3 days, and subsequently on the 7th and the 14th day after urokinase therapy. Fibrinolysis (determined by increased D dimer) occurred only when alpha 2-PI became unmeasurable with 96 x 10(4) or more units of urokinase administration, then persisted for more than 2 hours. TAT increased from 13.1 +/- 15.4 to 70.8 +/- 65.8 ng/ml soon after fibrinolysis occurred, indicating that thrombin generation occurred at the same time as fibrinolysis. The TPA PAI complex level before urokinase administration (26.4 +/- 6.4 ng/ml) was greater than the normal upper limit, indicating increased intrinsic fibrinolytic activity, then decreased after urokinase administration. These findings suggested that urokinase administration might affect the intrinsic fibrinolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Serial changes in hemostatic and fibrinolytic states induced by coronary thrombolytic therapy]. 806 82


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