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)

Increased plasminogen activator (PA) secretion has been observed in malignant cells and tissue and PA is thought to be involved in the processes of tumorigenesis, cancer invasion and metastasis. Recently two types of plasminogen activator--tissue type PA(tPA) and urokinase type PA(uPA)--have been detected in human plasma. In this study, to investigate the relationship between circulating PA and the malignant state, we measured the plasma PA concentrations (PA activity, tPA and uPA antigen) in 69 women with gynecologic malignancies (cervical cancer 50, ovarian cancer 19). These concentrations were compared to those in control groups of 33 women with benign gynecologic tumors (uterine tumor 8, ovarian tumor 25). An enzyme-linked immunoassay for tPA and uPA antigens was performed by the modified method described by Takada et al. (1986). PA activity was measured by the sensitive spectrophotometric assay of Verheijen et al. (1982). The blood samples were taken from an arm vein with a minimum of venous occlusion before treatment. There was no correlation between PA activity or uPA antigen levels and the malignant state. However, in the case of uterine tumors, a significantly higher concentration of tPA antigen (10.5 +/- 5.1 ng/ml) was found in patients with cervical cancer, in stage IV, than in those in the benign group (5.2 +/- 2.0 ng/ml). Moreover the tPA antigen concentration in cervical cancer, stage IV, was higher than in stages 0-III.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study on the plasma plasminogen activators in patients with malignant gynecologic tumors]. 251 Dec 60

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

Urokinase receptors on lymphocytes described in the paper link immune system of the body with fibrinolytic one, play a biological role in sano-++- and pathogenesis in aggravation of chronic purulent bronchitis, of focal and croupous pneumonia. A correlation between the trend in the expression of urokinase receptors on lymphocytes and changes in activity of plasminogen activator in the blood and urine was established: the more the expression, the more the activity. The method can serve a criterion of the treatment effectiveness+ in nonspecific inflammatory bronchial and pulmonary diseases and be helpful in designing methods of their treatment improvement.
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PMID:[Regulation of fibrinolysis by lymphocytes in inflammatory diseases of the bronchopulmonary system]. 256 May 7

Because alveolar fibrin is a prominent histologic feature of diffuse lung injury in baboons, we hypothesized that local abnormalities of pathways of fibrin turnover would favor fibrin deposition in the alveolar space. To test this hypothesis, procoagulant and fibrinolytic activities were characterized in serial bronchoalveolar lavage (BAL) of baboons with evolving diffuse alveolar damage (DAD) induced by exposure to 100% O2. BAL procoagulant activity, characterized mainly as the tissue factor-Factor VII complex, was markedly increased after induction of DAD. Extrinsic pathway inhibitor was likewise increased in BAL during evolving DAD but was insufficient to control coagulation. Urokinase-like fibrinolytic activity was usually detectable in baseline BAL but was undetectable after 7 d of O2. DAD BAL contained significantly increased plasminogen levels, plasmin inhibitor activity sufficient to neutralize all plasmin produced by BAL plasminogen activator found in control BAL and detectable plasminogen activator inhibitor-1. Antiplasmin activity was due, in part, to increased alpha 2-antiplasmin. These changes correlated with quantitatively increased alveolar fibrin deposition demonstrated by histologic and morphometric analyses. Multiple abnormalities of pathways of fibrin turnover occur concurrently in the alveolar compartment of the lungs of baboons with DAD, which collectively predispose to diffuse alveolar fibrin deposition.
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PMID:Local abnormalities of coagulation and fibrinolytic pathways that promote alveolar fibrin deposition in the lungs of baboons with diffuse alveolar damage. 273 51

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

Exercise to exhaustion was associated with the appearance in plasma of plasminogen activator (PA) in several mol wt forms, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with zymography. A number of active bands, all immunologically identified as tissue-type PA (t-PA), were observed. The major form had an apparent mol wt of approximately 60,000 and is due to free t-PA. The other strong bands had apparent mol wts of approximately 110,000 and 180,000. The 110,000 band, also present in pre-exercise samples, represents t-PA complexed with its major inhibitor (PAI-1), and the 180,000 band is due to t-PA complexed with C1 inhibitor. The released forms of t-PA were cleared rapidly after cessation of exercise at exhaustion. Urokinase-type PA (u-PA) activity was also identified in pre- and postexercise samples at an apparent mol wt of approximately 50,000. This is consistent with its being free u-PA; no complexed forms of u-PA were observed. Qualitatively similar changes in plasma PA were observed after venous occlusion. Small quantities of plasmin were generated after strenuous exercise, as observed by detection of plasmin-alpha 2-antiplasmin complex by two-dimensional immunoelectrophoresis in three of five subjects. This complex was cleared rapidly after cessation of exercise. Plasmin-alpha 2-antiplasmin complex was not detected in any of the subjects after venous occlusion.
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PMID:Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1. 295 96

Different possibilities of clinical thrombolysis are described. The classical therapy with streptokinase has the disadvantages of antigenicity and of a considerable influence on the clotting system. For this reason new methods of thrombolysis were examined. Urokinase, plasmin and t-PA are physiological substances and have, therefore, no antigenicity. However, plasmin also has a considerable influence on the clotting system whilst coagulation is only moderately influenced by urokinase. This necessitates additional administration of heparin when the dose of urokinase is low. t-PA is adsorbed onto the fibrin clot in the same manner as plasminogen. Thereby both substances acquire a considerably higher affinity for each other. In addition, inactivation by physiological inhibitors is considerably diminished after adsorption. This causes an almost exclusive lysis of the clot without alterations of systemic coagulation. Clinical results after application of the newer thrombolytic drugs are presented.
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PMID:[New methods of thrombolysis]. 295 74

A hybrid human cDNA was constructed by splicing of a cDNA fragment of tissue-type plasminogen activator (t-PA), encoding 5'-untranslated, the pre-pro region and amino acids Ser1-Thr263, with a cDNA fragment of urokinase-type plasminogen activator (u-PA), encoding amino acids Leu144-Leu411. The cDNA fragments were obtained from full length t-PA cDNA, cloned from Bowes melanoma poly(A)+ mRNA, and from full length u-PA cDNA, cloned from CALU-3 lung adenocarcinoma poly(A)+ mRNA. The hybrid (t-PA/u-PA) cDNA was expressed in Chinese hamster ovary cells and the translation product purified from the conditioned cell culture media. On SDS-gel electrophoresis under reducing conditions, the protein migrated as a single band with approximate Mr 70,000. On immunoblotting, it reacted both with rabbit antisera raised against human t-PA and against human u-PA. The urokinase-like amidolytic activity of the protein was only 320 IU/mg but increased to 43,000 IU/mg after treatment with plasmin, which resulted in conversion of the single-chain molecule (t-PA/scu-PA) to a two-chain molecule (t-PA/tcu-PA). The specific activity of the protein on fibrin plates was 57,000 IU/mg by comparison with the International Reference Preparation for Urokinase. Both the single-chain hybrid (t-PA/scu-PA) and the two-chain plasmin derivative (t-PA/tcu-PA) bound specifically to fibrin, albeit more weakly than t-PA. The t-PA/tcu-PA hybrid had a higher selectivity for fibrin than tcu-PA, measured in a system composed of a whole human 125I-fibrin-labeled plasma clot immersed in human plasma. Both hybrid proteins activated plasminogen directly with Km = 1.5 microM and k2 = 0.0058 s-1 for t-PA/scu-PA and with Km = 80 microM and k2 = 5.6 s-1 for t-PA/tcu-PA. CNBr-digested fibrinogen stimulated the activation of plasminogen with t-PA/tcu-PA (Km = 0.20 microM and k2 = 1.2 s-1). It is concluded that these t-PA/u-PA hybrid proteins combine, at least to some extent, the fibrin-affinity of t-PA with the enzymatic properties of u-PA (either scu-PA or tcu-PA), which in some assays result in improved fibrin-mediated plasminogen activation.
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PMID:Characterization of a fusion protein consisting of amino acids 1 to 263 of tissue-type plasminogen activator and amino acids 144 to 411 of urokinase-type plasminogen activator. 295 60

Various inducers endow human leucocytes with a procoagulant activity of tissue factor type. We have observed a novel plasma factor which in combination with streptokinase induces powerful leucocyte procoagulant activity. This streptokinase dependent factor (SKDF) is present in normal plasma or serum albeit quantitatively different in individual donors. The generation of tissue factor activity as a function of streptokinase-plasma complex shows a specific and saturable sigmoidal dose-response curve. The Hill plot shows a straight line with Hill coefficient, H = 2.2, suggesting a strong positive cooperativity for the binding of this streptokinase-plasma complex to the leucocyte surface receptor for the signal transduction leading to the biosynthesis of tissue factor apoprotein. It also suggests that the leucocyte surface receptor for streptokinase-plasma complex differs from that for endotoxin lipopolysaccharides. SKDF is of apparent high molecular weight. It does not appear to be an antibody to streptokinase since its level does not correlate with the level of antibodies to streptokinase, and it does not correlate with the antistreptolysin titre. Furthermore, SKDF does not bind to protein A. It has a narrow pH range of stability, and is destroyed at 56 degrees C, or at freeze-drying, Urokinase, another plasminogen activator, or plasmin were unable to activate SKDF to induce the leucocyte procoagulant activity. SKDF may play a role in thrombolytic therapy.
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PMID:A streptokinase dependent plasma factor (SKDF) induces leucocyte tissue factor activity. 297 1


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