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)

Expression of urokinase in murine and rat cells was performed by two recombinant constructs, one containing cDNA and the other--hybrid (cDNA/genome) variant of human urokinase gene conserving 7 introns of 10, in the eukaryotic retrovirus vector pPS-3-neo. DNA of both constructs was introduced into packaging cell line psi 2 by a standard Ca-phosphate transfection technique. Infection of mouse and rat fibroblasts BALB/c 3T3 and Rat I with virus particles, produced by transfected psi 2 cells, led to an integration into the host genome of one or two recombinant proviral copies. Stable expression and secretion into the culture medium of glycosylated high molecular weight human urokinase was observed for both cell types. For the hybrid gene construct, precise excision of intervening sequences was shown during transferring of genetic material from packaging to recipient cells.
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PMID:[Expression of human urokinase in inoculated rodent cells. Loss of introns during gene transfer using a retroviral vector]. 150 71

We describe the long term use for haemodialysis of the PermCath (Quinton, Seattle, Washington) dual lumen, jugular venous catheter (DLJVC) in 21 patients who had no apparent alternative means of access. The nineteen patients maintained in this manner for periods of 30 to 600 days (mean 233.2) included 6 patients dialyzed for over 12 months. Blood flows exceeded 250 mls/min and recirculation rates averaged 5.9%. Infection and insufficiency due to thrombosis were the major problems. In 8 patients (38.1%) infection required DLJVC removal; in three the catheter was immediately replaced over a guidewire along the same track under antibiotic cover and infection has not recurred. Insufficiency occurred in 10 patients (47.6%) and was successfully managed with oral anticoagulants, local instillation of urokinase (4 cases), systemic streptokinase (2 cases) or by changing the DLJVC over a guidewire (2 cases). We believe that the DLJVC is the long term access method of choice for patients in whom conventional access cannot be constructed.
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PMID:The use of dual lumen jugular venous catheters as definitive long term access for haemodialysis. 239 90

Some of the fibrinolytic and coagulation enzymes that monocytes produce are urokinase, a plasminogen activator (PA); a PA-specific inhibitor (PAI); and procoagulant activity (PCA), which has been characterized as tissue factor. Dengue infection in vivo is restricted to monocytes; however, it is unknown if dengue-infected monocytes undergo alterations in the production of PA, PAI, and PCA. This issue was addressed in studies in which monocytes were infected in vitro with dengue 2 virus in serum-free medium in the presence of enhancing antibody. No urokinase activity was detected in either control or infected cells or in their supernatants. Infection of monocytes with dengue 2 virus resulted in an almost threefold increase in PAI activity in cells and supernatants. No change in relation to the control was observed in PCA generated by the infected cells. These data indicate that dengue 2 infection enhances the production of PAI from monocytes without altering PA or PCA.
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PMID:Effect of dengue virus on procoagulant and fibrinolytic activities of monocytes. 250 55

Twelve Hickman catheters were inserted in nine children in order to establish access for haemodialysis or plasmapheresis. Catheters were implanted either through the external or internal jugular vein and the tip located in the right atrium or superior vena cava. Mean blood flow was 25-55 ml/min with single lumen catheters and 83-100 ml/min with double lumen catheters. Three catheters had to be removed because of obstruction, whilst seven remained in situ until an arteriovenous fistula had matured or renal function was restored. Infection in two cases was successfully treated with antibiotics and transient obstruction by urokinase instillation. Following catheter removal, angiographic studies showed that with one exception all catheterized vessels were obstructed, but this did not prevent from ipsilateral arteriovenous fistulas to mature satisfactorily.
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PMID:Hickman catheter for haemodialysis in paediatric patients. 315 34

Thirty-five patients with peripheral arterial occlusion were treated by intra-arterial infusion of low dose urokinase associated with bolus of lys-plasminogen. Systemic fibrinolysis was moderate, thrombolysis was achieved in 26 patients (74%). Only one patient required blood transfusion, five patients (14%) had distal emboli. Infection at the catheter entry site occurred in 2 patients, 3 patients experienced proximal embolism. Six patients required leg amputation, 4 died, in 2 of them deaths were related to arterial catheterization. Local thrombolysis with limited systemic fibrinolysis is associated to a high rate of catheter-related complications.
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PMID:Peripheral artery thrombolysis with urokinase-lys-plasminogen. A disappointing experience. 342 70

During the last three years, seven patients with severe intraventricular hemorrhage admitted to our clinic were treated with direct intraventricular infusion of urokinase. In each case, hemorrhage extended into the entire ventricular cavity and cast formation as well as an expansion of third and fourth ventricles were found. On the average, both the third and fourth ventricles became clear on the third day and the lateral ventricle on the ninth day after hemorrhage. Five of the seven patients showed good recovery or only moderate disability, and two died. Infection, convulsion, rebleeding, and peripheral or secondary hemorrhage due to the side effects of urokinase was not encountered during therapy. We conclude that this procedure can be applied effectively and safely in severe intraventricular hemorrhage.
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PMID:Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase. 747 22

Vascular catheter-related infection is an important cause of mortality and morbidity in hospitalized patients. The mean incidence of catheter-related bloodstream infection in hospitalized pediatric patients is 2.4 episodes per 1,000 days. Totally implantable central venous catheters may be associated with a lower risk of infection. Coagulase-negative staphylococci are the predominant cause and account for about one third of episodes of catheter-related bloodstream infection. The diagnosis of catheter-related bloodstream infection is often difficult because there are frequently no signs of inflammation around the catheter. Diagnosis depends on either a positive quantitative catheter culture yielding the same microorganism recovered from the bloodstream or differential quantitative blood cultures with significantly greater colony counts from blood drawn through the catheter than from blood drawn through a peripheral vein. Alternatively, probably catheter-related sepsis can be diagnosed when clinical sepsis is refractory to antimicrobial therapy but responds to catheter removal. Often these criteria are not met but catheter-related bloodstream infection is presumed because a common skin microorganism is isolated from the blood when clinical manifestations of bloodstream infection are present and there is no other apparent source of infection. Microorganisms causing catheter-related bloodstream infection gain access to the bloodstream predominantly from either the catheter insertion site or the catheter hub. Most catheter-related infections occurring shortly after catheter insertion probably gain access to the bloodstream by extraluminal migration along the catheter from the skin at the catheter insertion site. When catheters are in place for extended periods, especially greater than 30 days, the catheter hub probably plays a major role in microorganisms gaining access and then migrating endoluminally until reaching the bloodstream. Recently employed strategies for the prevention of catheter-related infections include topical antibiotics or antiseptics at the catheter insertion site, flush solutions containing vancomycin, and bonding antimicrobial agents to the catheter. Infection of peripheral and central venous catheters generally resolves after catheter removal. For tunneled silicone catheters, most episodes of catheter-related infection can be initially managed with antimicrobial therapy infused through the catheter without catheter removal. Staphylococcus aureus is generally more aggressive and associated with more complications than coagulase-negative staphylococci. Microorganisms that usually require catheter removal include Candida and Bacillus species. Adjunctive treatments of catheter infections include the use of urokinase. Catheter-related infection remains an important complication of vascular access. Novel prevention and treatment strategies are currently being investigated. In the near future bonding of antibiotics or other agents to catheters may become routine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intravenous catheter-related infections. 771 11

Numerous studies have demonstrated the importance of urokinase plasminogen activator (uPA) and its receptor, uPAR, in the processes of tumor progression and metastasis. Thus, the uPA/uPAR interaction may represent an important target for inhibiting metastatic disease. The baculovirus expression system was used to produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG) which could then be used for displacing uPA from the surface of tumor cells. The recombinant uPA-IgG fusion protein was placed under the control of either the viral polyhedrin promoter or a copy of the viral basic protein promoter. Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells. Infection of both cell types resulted in the production of secreted uPA-IgG. The molecular mass of the secreted protein as determined by SDS-PAGE was approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9 cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells. The uPA-IgG was readily purified using a combination of zinc chelate and sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater than 95% pure protein could be obtained per liter of culture medium collected at 72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus. BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA.
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PMID:Production of a urokinase plasminogen activator-IgG fusion protein (uPA-IgG) in the baculovirus expression system. 918 59

Tissue-type plasminogen activator (t-PA) is acutely released by endothelial cells. Although its endothelial storage compartment is still not well defined, t-PA release is often accompanied by release of von Willebrand factor (vWf), a protein stored in Weibel-Palade bodies. We investigated, therefore, whether t-PA is stored in these secretory organelles. Under basal culture conditions, a minority of human umbilical vein endothelial cells (HUVEC) exhibited immunofluorescent staining for t-PA, which was observed only in Weibel-Palade bodies. To increase t-PA expression, HUVEC were infected with a t-PA recombinant adenovirus (AdCMVt-PA). Overexpressed t-PA was detected in Weibel-Palade bodies and acutely released together with endogenous vWf by thrombin or calcium ionophore stimulation. In contrast, plasminogen activator inhibitor type 1 and urokinase were not detected in Weibel-Palade bodies after adenovirus-mediated overexpression. Infection of HUVEC with proinsulin recombinant adenovirus resulted in the storage of insulin in Weibel-Palade bodies, indicating that these organelles can also store nonendothelial proteins that show regulated secretion. Infection of AtT-20 pituitary cells, a cell type with regulated secretion, with AdCMVt-PA resulted in the localization of t-PA in adrenocorticotropic hormone-containing granules, indicating that t-PA can be diverted to secretory granules independently of vWf. Coinfection of AtT-20 cells with AdCMVt-PA and proinsulin recombinant adenovirus resulted in the colocalization of t-PA and insulin in the same granules. Taken together, these results suggest that HUVEC have protein sorting mechanisms similar to those of other regulated secretory cells. Although the results did not exclude an alternative storage site for t-PA in HUVEC, they established that t-PA can be stored in Weibel-Palade bodies. This finding may explain the acute coordinate secretion of t-PA and vWf.
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PMID:Storage of tissue-type plasminogen activator in Weibel-Palade bodies of human endothelial cells. 1039

Infections and venous thromboses are the major complications of central venous access catheters and ports. The frequency of thrombosis depends on the venous access systems used, their material, their diameters and the position of their tips. The lowest rate of thrombotic complications is seen with single or double lumen Hickman- or port catheters made of silicone with their tips in the lower half of the superior vena cava or in the right atrium. Antibiotics given preoperatively and heparin for at least 90 days after catheter placement must be recommended in oncological patients with a high risk of thrombosis. In case of thrombosis-related occlusion of the catheters low-dose urokinase and streptokinase can be helpful to restore the catheter's function. Else, therapy is identical to that of other types of thrombosis.
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PMID:[Deep venous thrombosis caused by central venous catheter]. 1040 16


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