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)

Urokinase was purified by affinity chromatography using 6-amino-naththamidine-(2), a new specific ligand based on the urokinase inhibitor beta-naphthamidine. Urokinase was firmly bound at pH 7.0 and could be eluted at pH 3.0. The protein which passed the column at pH 7.0 without being bound did not contain any urokinase activity. This is an important property because it can be utilized for raising a monospecific urokinase antiserum by absorbing unspecific antibodies with only a minor loss of antiserum titre.
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PMID:Purification of urokinase by a beta-naphthamidine affinity column. 50 6

Urokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose were administered to monitor potential toxicity revealing that Brinase, trypsin and SN 687 were very toxic at this concentration. Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo. The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.
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PMID:A comparative ex vivo study of plasminogen activators and proteases for fibrinolytic activity and side effects in rabbits. 57 12

Urokinase was highly purified by electrophoretical and immunological methods starting with a commercial urokinase preparation (UK-Leo). Contaminating serum proteins and enzyme activities migrated into opposite directions in agar gel electrophoresis which proved to be a valuable preparative method. The final purification achieved was 80,000 Ploug units/mg protein. Traces of albumin, alpha2HS-glycoprotein and alpha2-macroglobulin migrated towards the cathode together with UK in a multimolecular complex. Urokinase antibodies (rabbit) gave with the cathodic fraction 2 precipitation lines (Ouchterlony technique): the one precipitation line corresponded to urokinase (molecular weight on gel chromatography 32,000 daltons), the other corresponded to UK complexed with serum proteins. Urokinase antibodies completely suppressed UK activity in various commercial preparations. All these preparations showed immunological identity; on disc electrophoresis pure urokinase (32,000 daltons, 80,000 Ploug units/mg protein) still gave 2--3 bands suggesting the presence of isoenzymes.
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PMID:Preparation (agar zone electrophoresis) and immunological characterisation of urokinase. 57 94

Most of the technical problems associated with the fibrin plate method have been overcome in recent years with the exception of the long incubation period. This study was carried out to investigate plasminogen-enrichment as a means of shortening this period. Fibrin plates made up to contain 2.0 casein units of added plasminogen each, were opaque, firm, did not lyse spontaneously and yielded biometrically-valid parallel-line assays for streptokinase and urokinase after a 3 hour incubation period. Urokinase assays were more accurate than those for streptokinase probably because of the latter's shallow dose-response curve. Plasminogen-enrichment appears therefore to be a convenient way of producing a "rapid" fibrin plate requiring incubation for 3 hours compared with the usual 16 to 20 hours.
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PMID:The rapid fibrin plate - a method for plasminogen activator assay. 57 95

The effects of orthostatic changes on the excretion of urokinase were studied in healthy normal volunteers. Urokinase excretion rose (average +69%) significantly (p less than .005) while urine volume fell (average-59%) significantly (p less than .001) after the subjects had been standing. There was no difference between men and women nor was there an apparent diurnal variation in urokinase excretion of recumbent subjects. A relationship between urokinase excretion and sympathetic nervous system activity is suggested.
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PMID:Effect of orthostatic changes on urokinase excretion. 58 May 6

Toxicity of intravitreal urokinase was studied by injection of various doses of urokinase in primate eyes. Doses of 22,500 CTA units or less produced no toxic effects on the eye. Higher doses caused retinal degeneration, transient lens opacities, and cloudy vitreous. Urokinase was ineffective in clearing experimentally induced vitreous hemorrhage if injected as early as 24 hours after the intravitreal blood or as late as six months thereafter.
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PMID:Urokinase in experimental vitreous hemorrhage. 81 Jul 55

Fibrinolytic therapy was carried out in 59 patients suffering from a total of 60 deep venous thromboses of the iliac segment (n = 24), the femoropopliteal segment (n = 18), the deep calf veins (n = 2), or the subclavian vein (n = 16). 46 patients received streptokinase (SK), 4 were given urokinase (UK), and 10 were treated with streptokinase followed by urokinase (SK + UK). The duration of fibrinolytic therapy was between 19 and 596 hours (x = 166 +/- 111 hrs). Phlebographic examination was used to determine the location of the thrombotic occlusion as well as to evaluate therapeutic results. To assure sufficient anticoagulatory protection during therapy with streptokinase the dose of streptokinase was either reduced by steps of 20,000 U/hr to a minimum of 40,000 U/hr or heparin was added as a continuous infusion. Urokinase was administered with a mean loading dose of 75,000 IU followed by an average maintenance dose of 40,000 IU/hr; it was always given in combination with heparin. When therapeutic success was graded as complete/partial/no recanalisation, the following results were obtained: thrombotic occlusion up to 1 week old 35%/48%/17%; up to 2 weeks old 57%/14%/29%; 3 or 4 weeks old 12%/38%/50%; older than 4 weeks 13%/37%/50%. The two most common side effects were a fall of the hemoglobin and a rise of body temperature. Treatment with SK had to be interrupted for bleeding in two cases. One patient diet after rupture of the liver and of the spleen following development of subcapsular hematoma in these organs, 3 patients survived pulmonary embolism without major long-term impairment. Considering medical and social aspects (preservation of capability for working in young adults) it appears justified to administer fibrinolytic agents up to a thrombus age of 14 days, in some cases even up to a thrombus age of 28 days. Good results in cases of deep vein thrombosis of the lower limbs are often obtained only when fibrinolytic therapy is extended beyond 96 hours. It should be performed in intensive care units only. Follow-up examinations of the venous drainage capacity up to 2 years after fibrinolytic therapy document the good therapeutic effect that is warrented by streptokinase or urokinase induced complete recanalisation.
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PMID:[Fibrinolytic therapy in deep venous thrombosis of the upper and lower extremity]. 84 72

Urokinase is a plasminogen activator of human origin which breaks up the fibrin base of blood clots. When given as an intravitreal injection it produces hypopyon and glaucoma, both of which transient. In a series of 27 patients (34 eyes) with unresolved vitreous haemorrhage, this simple and relatively atraumatic treatment has produced marked objective improvement in 10, and greatly improved the life styles of a further 9. This series brings the total of reported cases to 93. When compared with recent American reports of surgical vitrectomy for vitreous haemorrhage, intravitreal urokinase appears to have a higher success rate, with a lower complication rate both in the short and long term. This study suggests that, despite the high cost of the purified enzyme, urokinase should be come the first line of attack in vitreous haemorrhage, vitrectomy being reserved for those patients who fail to respond.
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PMID:Urokinase in the management of vitreous hemorrhage. 91 29

Human alpha1-antitrypsin was prepared from fresh human plasma by (NH4)-SO4-precipitation, gel filtration, affinity chromatography on concanavalin A, ion exchange chromatography and isotachophoresis. Human urokinase (EC 3.4.99.26) (plasminogen activator from urine) with M, 46 000 and 36 000 was further purified from Urokinase Leo reagent preparation by gel filtration on Sephadex G-100 Superfine. The hydrolytic activity of urokinase on acetyl-glycyl-L-lysine methyl ester acetate (Ac-Gly-Lys-OMeAc) was inhibited in a strong time-dependent manner by alpha1-antitrypsin. Complex formation between enzyme and inhibitor could be demonstrated in crossed immunoelectrophoresis against anti-alpha1-antitrypsin and anti-urokinase serum as well as by sodium dodecyl sulphate polyacrylamide gel electrophoresis. The latter method revealed the formation of 1:1 and 2:1 molar enzyme-inhibitor complexes.
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PMID:Inhibition of urokinase by complex formation with human alpha1-antitrypsin. 108 51

The two stages in the activation of human plasminogen by urokinase have been examined kinetically in order to evaluate the significance of each stage in the activation process. The cleavage of the preactivation peptide from the NH2 terminus of native plasminogen (NH2-terminal glutamic acid) is clearly catalyzed by urokinase and is the rate-limiting first step in activation (Stage 1); this reaction is 20-fold slower than the conversion of the intermediate plasminogen (NH2-terminal lysine) to plasmin (Stage 2). Both lysine and its analogoue, epsilon-aminocaproic acid, exert two effects on the activation of native plasminogen. At low concentrations of these agents, activation is greatly accelerated. Analysis of activation in the presence and absence of these agents by sodium dodecyl sulfate gel electrophoresis indicates that the activation pathway is the same in both cases with the formation of a transient intermediate plasminogen; only the kinetics of proteolysis are altered. This enhancement in the rate of activation results solely from acceleration of the Stage 1 reaction; Stage 2 is essentially unaffected at low concentrations. Stage 1 is maximally enhanced (75-fold) at either 0.0025 M epsilon-aminocaproic acid or 0.025 M lysine and occurs 4 times more rapidly than Stage 2, which becomes the rate-limiting step at these concentrations. Plasmin also cleaves the preactivation peptide from native plasminogen and this reaction rate is enhanced by the same concentrations of lysine and epsilon-aminocaproic acid. These data suggest that lysine and epsilon-aminocaproic acid, which are known to bind to plasminogen and significantly alter its conformation, may thereby enhance preactivation peptide cleavage and consequently, plasminogen activation. At high concentrations, both Stages 1 and 2 are similarly inhibited by these agents, which suggests that this effect may be exerted by the direct inhibition of urokinase. The relative rates of preactivation peptide cleavage by the enzymes urokinase, plasmin, thrombin, and ancrod were also determined. Urokinase is 10 times more effective than plasmin in catalyzing this reaction and 1.8 X 10(4) times more effective than thrombin, while ancrod does not exert an effect. No plasmin is formed by either thrombin or ancrod.
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PMID:The importance of the preactivation peptide in the two-stage mechanism of human plasminogen activation. 115 Jun 67


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