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)

A canine model was developed to investigate coronary artery thrombolysis and reocclusion in the setting of endothelial cell damage and fixed stenosis, which simulate anatomic features occurring in patients with acute myocardial infarction. In open chest dogs, endothelial cell damage was produced in the left anterior descending coronary artery by external compression with blunt forceps, greater than 90% stenosis was obtained by an external constrictor and thrombosis was induced by instillation of thrombin and fresh blood in an isolated arterial segment. In the absence of stenosis, intravenous infusion of 750,000 U of streptokinase over 1 h caused reperfusion in five of six dogs in 34 +/- 25 min (mean +/- SD). Urokinase, 600,000 U intravenously over 30 min followed by 600,000 U over 30 min by the intracoronary route, induced reperfusion in three of four dogs in 65 +/- 23 min. Recombinant two chain tissue-type plasminogen activator (rt-PA) (G11021), infused intravenously at a rate of 15 micrograms/kg per min for 30 min or until reflow, induced reperfusion in all 12 dogs in 28 +/- 13 min. In the absence of coronary artery stenosis, spontaneous reocclusion did not occur within 2 h after the end of the infusion. In the presence of the coronary artery constrictor, which reduced the blood flow to 40 +/- 10% of baseline, streptokinase, urokinase and rt-PA caused coronary thrombolysis to proceed at comparable or only slightly slower rates. Cyclical reocclusion during or after the end of infusion of these thrombolytic agents, caused by platelet-rich thrombus, was almost invariably observed, generally within 30 min after the onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A canine model of coronary artery thrombosis with superimposed high grade stenosis for the investigation of rethrombosis after thrombolysis. 249 18

We investigated the increase of plasminogen activators (tPA and uPA) in the plasma during pregnancy. Both tPA and uPA antigens were found to increase after the third trimester of pregnancy and high levels of PAs persisted through the first stage of labor. The tPA antigen levels rose further for the first few hours post-partum, while the level of uPA antigen returned to normal immediately following childbirth. To clarify whether the uterus and/or placenta are involved in the increased levels of plasma PAs, the levels were measured in uterine venous blood in cases of caesarean sections. During the ante-partum period, the level of uPA antigen in the uterine venous blood was higher than that in the peripheral venous blood, while there was no significant difference between the levels of tPA antigen in peripheral blood and uterine venous blood. The level of tPA antigen in the uterine venous blood rose after delivery. In contrast, the level of uPA antigen declined immediately after delivery. These results suggest that (1) the placenta is the major source of the increased uPA antigen during pregnancy, (2) entire vascular system is involved in the increased tPA antigen during pregnancy, (3) a further increase in tPA after delivery is due to the release of this enzyme from the involuting uterus.
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PMID:Source of increased plasminogen activators during pregnancy and puerperium. 250 2

Immature mice were injected subcutaneously with 5 IU PMSG for 2 days to stimulate follicle development, which was followed by administration of 5 IU hCG to induce ovulation. The ovaries were removed at various periovulatory stages for preparing ovarian homogenates, granulosa cells and cumulus-oocyte complexes. The activity of plasminogen activator in the samples, separated by SDS-PAGE, were determined by fibrin-overlay technique. The results show that 15% of the gonadotropin-treated animals were ovulated 8h after hCG administration, about 6-8h earlier than that occurred in rat. Moreover, both tPA, and uPA activity were stimulated following PMSG treatment in ovarian homogenates and granulosa cells. Subsequent hCG injection further increased the two types of PA activity in a time-dependent manner, reaching maximum 4-8h after hCG treatment, and declined following ovulation. Greater uPA activity (70%) in the cultured mouse granulosa cells was found. It is, therefore, suggested that both tPA and uPA may be involved in the regulation of ovulation in mouse. The cumulus-oocyte complexes contained mainly tPA, which activity showed a time-dependent increase and reached a maximum between 12-24h after hCG treatment. Since cumulus-oocyte complexes collected from oviducts post ovulation still retain a considerable amount of tPA, the enzyme in the complexes may also play a role in the process of cumulus dispersion, oocyte transportation and implantation.
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PMID:[Plasminogen activator activity in mouse ovaries during periovulatory period]. 250 47

Urokinase and tissue-type plasminogen activators (u-PA and t-PA) were identified immunohistochemically in normal and inflamed human appendices by means of polyclonal and monoclonal antibodies. In addition, extracts of the tissues were analyzed for u-PA and t-PA by ELISA. Twelve appendices (five normal and seven with acute inflammation) were analyzed. In the normal appendices, there was a strong staining of the endothelial cells for t-PA, whereas there was negative staining for u-PA. In contrast, the endothelial cells in the inflamed appendices showed u-PA immunoreactivity, and negative or very weak reactions for t-PA. In the inflamed appendix, there was also a labeling of u-PA in fibroblast-like cells and in interstitial areas. The specificity of the staining was supported by a variety of staining controls and also by analysis of tissue extracts with ELISA, showing that on the average the inflamed appendices contained more than twice as much mu-PA per mg of protein as the normal appendices and less than one third of the amount of t-PA.
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PMID:Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the appendix. 250 79

Thrombolytic efficacy is directly related to thrombus age. We used recombinant tissue plasminogen activator (rt-PA), Streptokinase (SK) and Urokinase (UK) on a seven days old inferior vena cava thrombus model. "In vitro" clot lysis assays with fibrinogen-I125 were also evaluated with the same agents at 1, 3 and 7 days. Fibrinogen, D-D dimer and t-PA were measured. Experiments with 40 controls and 27 rt-PA treated animals showed a significant decrease in thrombus weight (8.5 +/- 1.1 mg) vs. (4.2 +/- 0.6 mg) (p less than 0.01). Fibrinogen concentration in rt-PA group decreased significantly (1032 +/- 123 mg/dl) vs. (202 +/- 32 mg/dl) (p less than 0.001). "In vitro" rt-PA showed a marked lytic effect in a wide range (100-4 IU/ml). Fibrin selective agents as rt-PA may be more effective than non selective ones in the treatment of fully developed thrombus.
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PMID:Thrombus age and tissue plasminogen activator mediated thrombolysis in rats. 251 87

The secretion of plasminogen activator by seminiferous tubules at defined stages of the epithelial cycle is influenced both by neighboring spermatogenic cells and by hormones. We have used cRNA probes for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators to analyze their mRNA levels in different stages of the epithelial cycle. Urokinase-type PA mRNA was most abundant in stages VII-VIII, while tPA mRNA levels showed smaller variations between the different stages. Both FSH and (Bu)2cAMP increased the steady-state level of tPA mRNA and tPA production without affecting those of uPA in stages VII-IX in vitro, whereas retinoic acid treatment selectively increased the concentration uPA mRNA and uPA production in stages II-VI. The results show that the expression of the uPA and tPA genes is differentially regulated in specific stages of the rat seminiferous epithelium.
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PMID:Regulation of urokinase- and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium. 253 92

Mouse cerebellar cells in culture secrete tissue plasminogen activator (tPA) into the culture medium. Fibrin overlays have shown tPA to be associated with granule neurons in these cultures. This cell associated tPA can be displaced by extensive washing of the cells or by a brief lowering of the pH (less than 4), which leads to a loss of fibrinolytic activity by the cells. Incubation of these fibrinolytically inactive cells with exogenously added murine tPA leads to the restoration of the fibrinolytic activity, indicating the presence of tPA binding sites on these granule neurons. Using 125I-tPA, the binding to cerebellar granule neurons is rapid, saturable, specific, high affinity (Kd = 50 pM) and reversible. Both murine and human tPA compete with 125I-tPA for binding, with both murine and human urokinase (uPA) as well as human thrombin and plasminogen fail to compete. Neither the catalytic site nor the carbohydrate moiety of tPA appear to be involved in the binding, since both diisopropyl-fluorophosphate-treated tPA and endoglycosidase-H-treated tPA compete with 12I-tPA for binding. Furthermore, epidermal growth factor does not compete well with tPA for binding even at a 10:1 molar excess, suggesting that the epidermal growth factor-like (EGF) domain of tPA may not be involved in the binding mechanism. Autoradiography and antibody immunofluorescence show the specific tPA binding is to granule neurons in these cultures. Thus, granule neurons possess tPA receptors on their surface, where this protease binds retaining is functional activity and may play a role in cell and axon migration.
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PMID:Characterization of 125I-tissue plasminogen activator binding to cerebellar granule neurons. 254 26

Plasma protein C inhibitor (PCI) was purified to homogeneity (greater than 95%) with good recovery (greater than 25%) and reproducibility, and the inhibition of a number of blood clotting and fibrinolytic enzymes by purified PCI was studied. PCI inhibited activated protein C (APC), two-chain urokinase (2c-uPA), two-chain tissue plasminogen activator (2c-tPA), thrombin, factor Xa, plasma kallikrein and factor XIa, and this inhibition was accelerated by heparin. The inhibition of each enzyme was accompanied by formation of enzyme inhibitor complexes and by degradation of the inhibitor to lower molecular weight derivatives. Plasma kallikrein and factor XIa cleaved PCI of native Mr = 57,000 into two products with Mr = 54,000 and 52,000 whereas the other enzymes converted the PCI to a product with Mr = 54,000. PCI did not detectably inhibit alpha-factor XIIa or plasmin. Kinetic studies using PCI yielded the following second-order rate constants for inhibition of human APC, 2c-uPA, 2c-tPA, thrombin, factor Xa, kallikrein and factor XIa respectively: 0.65 x 10(4), 0.22 x 10(4), 0.08 x 10(4), 0.61 x 10(4), 2.01 x 10(4), 6.50 x 10(4), and 9.03 x 10(4) M-1s-1 in the absence of heparin and 1.58 x 10(6), 0.43 x 10(6), 0.03 x 10(6), 0.52 x 10(6), 0.09 x 10(6), 0.18 x 10(6) and 0.74 x 10(6) M-1s-1 in the presence of optimal concentrations of heparin. The rate constants for the inhibition of factor XIa and 2c-uPA by PCI suggest a possible role of PCI in the physiologic regulation of these enzymes. The second order rate constants for inhibition of bovine APC and Gla-domainless bovine APC by human PCI were 0.61 x 10(4) and 0.26 x 10(4) M-1s-1 in the absence of heparin and 0.54 x 10(6) and 0.71 x 10(6) M-1s-1 in the presence of heparin, respectively. Calcium ions (0.05 to 4 mM) did not affect these rate constants. The results obtained with normal and Gla-domainless APC indicate that the Gla domain of APC is not required for inactivation by PGI and is not essential for the heparin stimulation of this reaction.
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PMID:Purification and characterization of plasma protein C inhibitor. 255 Oct 64

After reviewing the principles, results and complications of thrombolytic therapy with "classical" agents (Streptokinase and Urokinase) used via intravenous, intraarterial route, or intraoperatively, and with more "modern" agents (APSAC, scuPA, tPA), we discuss the future of thrombolysis in the treatment of arterial ischemia of the limbs. Several items need to be clarified: --indication of thrombolysis among other treatments, mainly surgery, of arterial ischemia depends on the clinical staging of ischemia, its causes and the site of arterial obstruction; --method of delivery of the thrombolytic agent must provide the highest local concentration and the lowest systemic side effects; --efficacy of each thrombolytic agent must be analyzed when used in peripheral arterial ischemia, but also in other diseases such as myocardial infarction.
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PMID:Results of thrombolysis in the treatment of arterial ischemia of the limbs according to mode of administration. 269 81

The ability of the chick embryo chorioallantoic membrane (CAM) to withstand invasion by tumor cells can be intentionally compromised by altering its morphological integrity. Using a newly developed quantitative assay of invasion we showed that intact CAMs were completely resistant to invasion by tumor cells, wounded CAMs did not pose a barrier to penetration, and CAMs that were wounded and then allowed to reseal displayed partial susceptibility to invasion. The invasion of resealed CAMs required catalytically active plasminogen activator (PA) of the urokinase type (uPA); the invasive efficiency of tumor cells was reduced by 75% when tumor uPA activity or tumor uPA production was inhibited. The invasive ability of human tumor cells, which have surface uPA receptors but which do not produce the enzyme, could be augmented by saturating their receptors with exogenous uPA. The mere stimulation of either uPA or tissue plasminogen activator production, in absence of binding to cell receptors, did not result in an enhancement of invasiveness. These findings suggest that the increased invasive potential of tumor cells is correlated with cell surface-associated proteolytic activity stemming from the interaction between uPA and its surface receptor.
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PMID:In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. 284 51


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