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

Adherence ability to catheter materials for intravenous use of coagulase-negative staphylococci (CNS) which is frequently isolated from prosthetic implants and medical devices inserted into the body was studied, and the mechanism of catheter-associated infections and the prevention against that were discussed. Difference of the adherence ability of CNS to various kinds of catheter materials was found, and adherence ability to the catheter materials was correlated with that of human epithelial cells in culture. CNS isolated from intravenous catheters had higher adherence ability to the human epithelial cell cultures than isolates from other clinical sources. Among 4 kinds of catheter materials, including ethylene vinyl acetate (EVA), polyvinyl chloride (PVC), silicone (Sil) and polyurethane (PUR), the adherence ability of CNS on the EVA containing barium was highest, and Sil treated with tungsten showed the lowest. The physicochemical properties of both the bacteria and the catheter materials, hydrophobicity of the bacterial cultures and the catheter materials, negative charges on surface of the bacteria, surface structure of the catheter materials, additives to the catheter materials, and coating the catheter surface gave great effects on the adherence of CNS to the catheter materials. In addition, as biofactors, fibronectin and PROTEAMIN-HICALIQ solutions enhanced the adherence of CNS. These results suggested that catheter materials having a smooth surface and higher hydrophobicity, treated with tungsten and coated with urokinase were effective on the suppression of the adherence to catheter materials. In addition to the improvement of catheter materials, aseptic procedures in catheterization were thought to be critical for the prevention of catheter-associated infections.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Adherence ability of coagulase-negative staphylococci to catheter materials]. 207 72

We have previously reported paradoxical prothrombotic effects manifest by elevations of fibrinopeptide A (FPA) after administration of streptokinase to patients with acute myocardial infarction. To characterize mechanisms responsible and their dependence on streptokinase (SK) as opposed to other activators of the fibrinolytic system, the present study was performed to compare effects of streptokinase, tissue-type plasminogen activator (t-PA), and urokinase on plasma and on purified prothrombin in concentrations similar to those achieved pharmacologically. The effects of plasmin were assessed to determine the extent to which the elevations of FPA seen could be attributed to activation of plasminogen. Elevations of FPA were observed after incubation of each of the activators with citrated plasma at 37 degrees C for 60 minutes. However, they were most marked with streptokinase (64.5 +/- 4.6 pmol FPA/ml (mean +/- SE) with 100 IU SK/ml, and 77.6 +/- 5.0 pmol/ml with 500 IU SK/ml). Elevations of FPA induced by streptokinase were attenuated by 100 IU/ml heparin [15.2 +/- 1.9 pmol/ml after 100 IU of SK (p less than 0.001 compared with results with streptokinase without heparin)]. Human plasmin, 2.5 CTA/ml, caused changes similar to those induced by streptokinase. The minimal elevations of FPA induced by t-PA or urokinase (less than 10 pmol/ml without heparin) were not significantly attenuated by heparin. Incubation of barium citrate adsorbed plasma (vitamin K factor depleted) with streptokinase markedly attenuated elevation of FPA. Addition of prothrombin (1.5 microM) and streptokinase (100 IU/ml) to the barium citrate adsorbed plasma elicited elevations of FPA similar to those induced by streptokinase in citrated plasma. Amidolytic activity with the "thrombin" substrate H-D-phenylalanyl-L-pipecolyl-L-arginine-p-nitroanilide dihydrochloride (S-2238) was evident when streptokinase, plasminogen (0.24 microM), and prothrombin (1.5 microM) were incubated in buffer. Thus, concentrations of streptokinase that are low in terms of therapeutic blood levels activate prothrombin in plasma, likely due to activation of plasminogen. Neither tissue-type plasminogen activator nor urokinase in pharmacologically comparable concentrations increase thrombin activity appreciably perhaps because of less intense activation of plasminogen. Consideration of the prothrombotic effects observed may be relevant to selection of specific agents for therapeutic thrombolysis, to appropriate titration of dose, and to the need for the use of heparin conjointly with particular activators of the fibrinolytic system such as streptokinase.
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PMID:Differential effects of activation of prothrombin by streptokinase compared with urokinase and tissue-type plasminogen activator (t-PA). 313 87

Percutaneous aspiration thromboembolectomy (PAT) was used as an angioplastic tool to remove from arteries of the lower limbs thromboembolitic material originating from any source. PAT was performed with a custom-designed catheter/sheath system, alone or in combination with balloon dilatation and/or local lytic infusion therapy with streptokinase or urokinase. PAT completed the restoration of blood flow, thus improving the results of the preceding angioplastic interventions. Clinical improvement was high, with 93% success (42 of 45 procedures). Only one below-the-knee amputation occurred, and could not be prevented. No patient became worse because of PAT intervention. The Fogarty catheter technique remains the method of choice for removing emboli within the aorto-iliac region, but in the smaller vessels below the inguinal ligament-especially in the distal superficial femoral, popliteal, and tibial regions--in our experience PAT is superior. This has been substantiated also in studies of laboratory animals, using barium-impregnated emboli.
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PMID:Percutaneous aspiration thromboembolectomy. 315 42

A case of generalized peritonitis, secondary to a perforation of the rectosigmoid colon during barium-enema roentgenography, is presented. The patient required immediate surgical intervention with the prime importance of the treatment being removal of as much of the contaminating materials as possible. This was done successfully with irrigation and wiping, using urokinase solution. Peritoneal lavage with urokinase solution was also carried out in the early postoperative period. Fluid replacement with careful monitoring of fluid and electrolyte balance is essential before, during, and after the surgical procedure. Adequate antibiotic therapy and careful respiratory and nutritional support are also important.
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PMID:Barium peritonitis. Report of a case and review of the literature. 399 52

We report the isolation of a specific protease zymogen from chicken plasma. The purification procedure involves barium citrate precipitation, ammonium sulfate fractionation, removal of plasminogen and plasmin on lysine-Sepharose, followed by anion and cation exchange, and gel permeation chromatography. Based on quantitative radioimmunoassay the zymogen is present in plasma at a concentration of 160 mg/liter, and it is obtained by our procedure in highly purified form with a yield of 1.4%. The single polypeptide chain contains an NH2-terminal alanine residue. The native molecule migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 84,000 under reducing conditions. It can be identified as an inactive proenzyme because it has very low amidolytic activity, does not react with the fluorescent active site titrant 4-methyl-lumbelliferyl p-guanidinobenzoate, and does not incorporate radioactive [3H]diisopropylfluorophosphate. It is very susceptible to limited proteolysis which converts it to an active enzyme with trypsin-like specificity. The active enzyme, likewise a single polypeptide chain, migrates as a doublet with apparent molecular weights of 39,000 and 40,000. Its amidolytic activity with synthetic peptide substrates is at least 40-fold higher than that of the proenzyme, it reacts efficiently with 4-methylumbelliferyl p-guanidinobenzoate, and incorporates [3H]diisopropylfluorophosphate while undergoing irreversible inactivation. The enzyme appears to be a reasonably efficient plasminogen activator in zymographic gels, but not in solution. With human high molecular weight kininogen as substrate the enzyme was about 25% as efficient as human plasma kallikrein. It lacks any plasminogen-independent proteolytic activity with other protein substrates, and it hydrolyzes small peptide substrates designed for both human kallikrein and urinary urokinase, respectively. Inhibition studies with peptide chloromethyl ketones indicate enzymatic properties closer to human plasma kallikrein than to the human plasminogen activator urokinase (EC 3.4.21.31). The chicken plasma enzyme and the plasminogen activator from the conditioned media of Rous sarcoma virus-transformed chick embryo fibroblasts treated with tumor promoter are different by criteria of tryptic peptide maps, and amino acid composition and enzymatic specificity. The designations chicken plasma prekallikrein plasminogen proactivator and chicken plasma kallikrein plasminogen activator are proposed for the zymogen and enzyme forms, respectively. Using rabbit antibodies against the proenzyme we developed a solid phase immunoadsorption procedure that allowed us to isolate the protein with an overall yield of 11.4%.
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PMID:A proenzyme from chicken plasma similar to human plasma prekallikrein. 655 13

The effect of a 17-kringle form of recombinant apo(a) [r-apo(a)] on in vitro fibrin clot lysis was studied. In these assays, fibrin clots were formed in the wells of microtiter plates, and lysis of the clots was monitored by measurement of the turbidity at 405 nm. The results indicate that r-apo(a) produces a dose-dependent antifibrinolytic effect in clots formed using either purified components or barium-adsorbed plasma. This effect was found to be independent of clot structure, since lysis of clots formed using both high and low concentrations of thrombin was prolonged by r-apo(a) to the same extent. The two components of the antifibrinolytic effect of r-apo(a) were determined to be (i) attenuation of tPA-mediated plasminogen activation (the major component) and (ii) inhibition of plasmin degradation of fibrin, although r-apo(a) did not directly attenuate plasmin activity, as measured by S-2251 hydrolysis. r-Apo(a) interfered most substantially with tPA-mediated activation of Glu-plasminogen and less substantially with tPA-mediated Lys-plasminogen activation and urokinase-mediated activation of plasminogen. In summary, we have demonstrated that apo(a) is able to attenuate fibrin clot lysis in vitro, primarily as a consequence of the interference by apo(a) with tPA-mediated Glu-plasminogen activation. These studies illuminate possible mechanisms by which Lp(a) may contribute to the development of vascular disease in vivo.
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PMID:Antifibrinolytic effect of recombinant apolipoprotein(a) in vitro is primarily due to attenuation of tPA-mediated Glu-plasminogen activation. 771 Oct 34

The inducible uPA enhancer contains two phorbol ester responsive elements: the combined PEA3/AP-1A and a downstream AP-1B site. The integrity of all three sites is essential for enhancer activity. The interposed 74 bp long DNA region (COM, Cooperation Mediator) is in turn required for the synergistic action of the PEA3/AP-1 and AP-1 sites. Here we present a characterization of the COM sequence: our results show that COM and COM-binding proteins (UEF, Urokinase Enhancer Factors) may play a structural role in the induction of the uPA enhancer by phorbol-myristate-acetate (TPA). (1) COM has a bipartite structure (uCOM and dCOM) and each half contributes by about 50% to the COM-mediated TPA induction. (2) COM function is strictly dependent on its position, but not on its orientation and neither the entire COM nor individual UEF-binding sites can directly transactivate a test promoter. (3) The requirement for COM in TPA-induction is partly eliminated by the deletion of COM sequence. However, also in the COM-deleted enhancer, integrity of the PEA3/AP-1A and AP-1B sites is essential for enhancer function. We conclude that COM and COM-binding proteins provide a structural surface which facilitates the cooperation between the transactivator proteins bound at the PEA3/AP-1A and AP-1B sites. Sequences homologous to uCOM are found in the promoters of other inducible genes, coding for proteases, cytokines and chemokines: for example, in the promoter of the MIP-1alpha/LD78 chemokine gene, a 15/18 nucleotides identity is found in a region mediating positive and negative functions in TPA induction. Thus, COM-like elements represent a general enhancer function which, although lacking an intrinsic transactivating capacity, modulates the synergism between transcription factors bound to distant sites.
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PMID:Functional characterization of COM, a DNA region required for cooperation between AP-1 sites in urokinase gene transcription. 900 Jan 29

The enhancer of the inducible urokinase gene depends on three essential but not sufficient transactivating elements, an upstream PEA3/AP-1A and a downstream AP-1B site. Enhancer activity also requires the interposed 74-base pair-long cooperation mediator (COM) region that allows transcriptional synergism between the transactivating sites. The 5'-half of COM (uCOM) forms four retarded complexes with HeLa or Hep-G2 nuclear proteins (UEF-1-4). We have identified the binding sequence for UEF-4 and generated uCOM elements uniquely mutated in the UEF-4-binding site or uniquely binding UEF-4. Introduction of these and other mutations in the context of the urokinase enhancer showed that all uCOM sites are important for enhancer activity but that UEF-4 and UEF-1 plus UEF-2/3 can substitute for each other, suggesting functional redundancy of urokinase enhancer factors. UEF-4 was purified from HeLa nuclear extract by affinity chromatography and shown to contain two polypeptides of 105 and 65 kDa, respectively, of which at least the former was endowed with DNA binding activity.
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PMID:Characterization of UEF-4, a DNA-binding protein required for transcriptional synergism between two AP-1 sites in the human urokinase enhancer. 929 42

Chronic, intermittent GI bleeding is defined as obscure when routine diagnostic examinations of the GI tract, including barium and endoscopic studies, fail to reveal the cause of bleeding. Our patient had significant bleeding and extensive evaluation including upper endoscopy, small bowel enteroscopy, enteroclysis, colonoscopy, and provocative angiography with urokinase, without the source of bleeding detected. This report describes a noninvasive novel approach using helical CT scanning with water as oral contrast and rapid injection of intravenous iodinated contrast material and thin slices obtained to diagnose the site of recurrent, obscure GI bleeding related to cholesterol crystal embolization to the small intestine.
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PMID:Detection of bleeding due to small bowel cholesterol emboli using helical CT examination in gastrointestinal bleeding of obscure origin. 1060 30

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of other genes by transcriptional inhibition or translational repression. miR-34a is a known tumor suppressor gene and inhibits abnormal cell growth. However, its role in other tumorigenic processes is not fully known. This study aimed to investigate the action of miR-34a on cell invasion. We found that miR-34a is expressed at various levels in cervical cancer (HeLa, SiHa, C4I, C33a and CaSki) and trophoblast (BeWo and JAR) cell lines. Transient forced expression of miR-34a did not affect the proliferation of these cell lines. Computational miRNA target prediction suggested that Notch1 and Jagged1 were targets of miR-34a. By using functional assays, miR-34a was demonstrated to bind to the 3' untranslated regions of Notch1 and Jagged1. Forced expression of miR-34a altered the expression of Notch1 and Jagged1 protein as well as Notch signaling as shown by the response of Hairy Enhancer of Split-1 protein to these treatments using western blot analysis. Forced expression of miR-34a suppressed the invasiveness of HeLa and JAR cells. By using gamma-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) that interfered Notch signaling and RNA interference that knockdown Notch1 expression, we confirmed that downregulation of Notch1 reduced the invasiveness of the cells. Transfection of intracellular domain of Notch nullifies the effect of miR-34a on the invasiveness of the cells. Besides, we identified that miR-34a affected cell invasion by regulating expression of urokinase plasminogen activator through Notch. Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme.
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PMID:MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. 2035 Oct 93


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