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)

A water-insoluble urokinase (ins-UK) was prepared by covalent coupling to an electrostatically neutral polyacrylamide derivative. The esteratic activity retained by the bound enzyme is about 70 percent of that of the soluble urokinase (UK). Comparative kinetic studies of these two forms of the enzyme were undertaken on lysine esters: N-alpha-acetyl-L-lysine-methyl ester (ALEe) and N-alpha acetylglycyl-L-lysine methyl ester (AGLMe). It was first observed that these substrates both exhibit a marked inhibitory effect toward soluble UK, whereas this phenomenon was less manifest with the insoluble form of the enzyme. Michaelis constants and maximal velocities measured at 33 degrees C, for UK and ins-UK, were identical when ALMe was used, but slightly different with AGLMe. Determination of initial velocities, at a series of pH values shows only minimal differences in the behavior of the soluble enzyme with respect to that of the insoluble form. However, over a range of temperatures, differing Km values for these two enzyme forms were obtained using AGLMe as the substrate. These last results suggest possible interactions between the substrate and the insoluble carrier of the enzyme.
 ...
PMID:Kinetic studies on soluble and insoluble urokinases. 24 73

Fresh retracted clots are known to be poorly lysable by fibrinolytic agents. We have studied whether lysis of retracted clots could be enhanced by bulk transport in comparison to pure diffusion of plasma containing urokinase (400 IU/ml) into the clots. Cylindrical retracted blood clots were occlusively glued by a polyester into plastic tubes and put in contact with plasma through the clot bases. One group of clots (perfused clots, n = 10) was placed under a pressure difference of 6 kPa (60 cm H2O) which resulted in an average plasma flow of 0.97 +/- 0.34 microliters/min through the clot during the first hour. Another group of clots (non-perfused clots, n = 10) was incubated in the lytic plasma without a pressure difference. Clot sizes were measured during lysis by magnetic resonance imaging (MRI). Channels representing lysed areas penetrated into perfused clots with a velocity of 5.4 +/- 1.6 mm/h (n = 10), whereas the boundaries of non-perfused clots subsided with a velocity of less than 0.1 mm/h. Eight of the 10 perfused clots were recanalized after 8 h and the sizes of the perfused group were reduced to 64.0 +/- 10.7% of the initial values. The relative sizes of non-perfused clots after 8 h remained significantly higher: 95.0 +/- 1.3%, p < 0.005. In a separate experiment good agreement was obtained between the measured clot sizes by MRI and the residual radioactivity of 125I-fibrin in the clot.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lysing patterns of retracted blood clots with diffusion or bulk flow transport of plasma with urokinase into clots--a magnetic resonance imaging study in vitro. 128 80

Effects of water-miscible organic solvents added to an aqueous buffer on the activity of several serine proteinases were studied. Plasmin in particular showed a dramatic difference in activity depending on the hydrophobicity of the added organic solvent through a combination of Km and kcat effects. An inverse linear correlation between the polarity of the mixed solvent and the log (kcat/Km) of plasmin activity was observed for both H-D-Val-Leu-Lys-p-nitroanilide (S-2251) and pro-urokinase as the substrate. The activity of plasmin was less dependent on the polarity of the added solvent when other chromogenic substrates were employed that contained an arginyl residue in the P1 site.
 ...
PMID:Medium effects on the kinetics of human plasmin. 138 9

In anesthetized rabbits with pulmonary embolized thrombi the interactions of saruplase (recombinant unglycosylated single-chain urokinase-type plasminogen activator, CAS 99149-95-8) with acetylsalicylic acid (ASA), glyceryl trinitrate (nitroglycerin, GTN), heparin, and the antifibrinolytics tranexamic acid and aprotinin have been studied. Lysis rates were evaluated as reduction of the weight and as reduction of the incorporated 125J-fibrin content of the embolized thrombi. In untreated controls the spontaneous 125J-fibrinolysis was 8.3 +/- 0.7% and the thrombus weight was reduced by 55.3 +/- 4.5% (mainly due to loss of H2O) at 195 min after the thromboembolization. Infusion of saruplase (21.5 micrograms/kg.min) for 60 min significantly increased the 125J-fibrinolysis to 36.8 +/- 3.7% and the reduction of the thrombus weight to 69.9 +/- 2.1%. ASA (50 mg/kg p.o.) by itself did not exert a lytic effect; in combination with saruplase ASA insignificantly augmented the 125J-fibrinolysis rate and significantly further increased the thrombus weight reduction. GTN (5.0 micrograms/kg.min i.v.) neither influenced the spontaneous nor the saruplase-mediated lysis rates. Treatment with heparin (200 IU/kg i.v.-bolus plus 50 IU/kg.min i.v.-infusion) resulted in significant greater thrombus weight reduction than observed in untreated controls; in combination with saruplase heparin significantly intensified the lytic effect. Tranexamic acid (30 mg/kg i.v.) and aprotinin (30.10(3) KIU/kg i.v.) completely abrogated the lytic effect of saruplase. Treatment with saruplase alone produced an insignificant decrease of the plasma level of fibrinogen by 23% to 200 +/- 20 mg/dl. ASA, GTN and aprotinin did not influence this slight fibrinogenolysis in saruplase-treated animals. A slight decrease of plasma fibrinogen levels was observed by heparin, whereas the decrease by tranexamic acid was significant.
 ...
PMID:Interactions of saruplase with acetylsalicylic acid, heparin, glyceryl trinitrate, tranexamic acid and aprotinin in a rabbit pulmonary thrombosis model. 170 27

In the normal stomach of male rats marked differences in plasminogen activator activity (PAA) and plasmin inhibition (PI), but not in plasminogen activator inhibition (PAI), were noted among cardiac area, body and pyloric region. Chronic ethanol consumption (for 15 or 30 days) at the concentration of 6% or 12% in the drinking water induced an increase in PAA in the pyloric region and the body of the stomach (the higher concentration after 15 days and both concentrations after 30 days). The response was time- and dose-dependent. At the cardiac area no change of PAA was noted. Ethanol at both concentrations induced after 30 days a decreased PAI in the pyloric region and the body of the stomach, which was expressed against u-PA, but not against t-PA. A decreased PI was noted at both concentrations of ethanol after 30 days only in the pyloric region. Therefore, changes in PAA, PAI and PI after chronic ethanol consumption were dependent on the concentration, the period of the consumption and the area along the gastric wall.
 ...
PMID:Enhancement of plasminogen activator activity in the gastric wall after chronic ethanol consumption. 182 83

Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.
 ...
PMID:Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro. 187 17

The authors prospectively treated 10 consecutive patients with multiloculated empyemas with intracavitary instillation of urokinase via a percutaneous drainage catheter. Urokinase (100,000 IU) in 100 mL of 5% dextrose in water was instilled into the pleural cavity via a percutaneous drainage catheter. After overnight clamping, the catheter was opened and the empyema drained with use of negative suction (20 cm H2O). Intermittent irrigation of the catheter with normal saline was performed to prevent clogging of the catheter. Complete drainage of multiloculated empyemas was accomplished in nine patients by means of intracavitary instillation of urokinase via a single 8-F catheter. One patient showed complete drainage of multiloculated empyema, but recurrent empyema appeared in the site of a previous tube thoracostomy. A total of 100,000-700,000 IU (mean, 400,000 IU) of urokinase were needed for complete drainage in all patients. Plasminogen and fibrin degradation product levels in empyema fluid were determined before instillation of urokinase to demonstrate any fibrinolytic action. No complications occurred.
 ...
PMID:Treatment of thoracic multiloculated empyemas with intracavitary urokinase: a prospective study. 202 90

A case of pulmonary embolism associated with diabetes insipidus is reported in an 18-year-old male. The patient, who had been treated with DDAVP for diabetes insipidus and hydrocortisone for hypocorticism for two years after first operation for the removal of craniopharyngioma, was admitted with recurrence of that tumor. Diabetes insipidus immediately after second operation was controlled with intermittent drip infusion of a small amount of aqueous pitressin under monitorings of body weight hourly using a patient weighing system to keep the weight changes within +/- one kilogram. Serum and urine electrolytes levels, osmolarity, and free water clearance were also monitored every three hours to maintain water-electrolytes balances appropriately. Postoperative course had been uneventful except that CSF rhinorrhea occurred 7 days after operation. The patient was, then, kept in bed with horizontal plane to avoid further leakage of CSF. Two days later, he developed chest pain suddenly with tachypnea, tachycardia, and general cyanosis. The arterial-BGA showed PaO2 of 53.5mmHg and PaCO2 of 35.3mmHg in room air. The definite diagnosis of pulmonary embolism was made by technetium microaggregate lung perfusion scans and by pulmonary angiograms. The patient was treated with heparin, 15000IU/day, and urokinase, 720000IU/day. The symptoms due to pulmonary embolism had improved gradually within a couple of weeks. Recent articles have shown an unexpected high incidence of deep vein thrombosis and pulmonary embolism in neurosurgical patients associated with the elevation of blood coagulability. Brain tumors, especially suprasellar mass with hypothalamic dysfunction have been suggested to cause thromboembolic disorders frequently. The clinical course was described and factors causing pulmonary embolism on this patient was discussed.
 ...
PMID:[A case of pulmonary embolism with diabetes insipidus developed after removal of craniopharyngioma]. 233 47

Rats received 0.1% lead acetate in their drinking water for 3 weeks or for 6 weeks, at which time renal brush border fractions were obtained for measurement of enzyme activity. Renal brush border preparations from Pb2+-exposed rats exhibited statistically significant decreases in the activity of gamma-glutamyl transpeptidase and alanine aminopeptidase after 3 or 6 weeks of treatment. There was an increase in the activity of alkaline phosphatase which was statistically significant after 3 weeks of Pb2+ exposure. The (Na+,K+) adenosine triphosphatase activity and urokinase activity, located in the basolateral membrane fractions, were unchanged by Pb2+ exposure, as were the protein and phospholipid contents of the brush border fractions. The results are compared to those following acute exposure to Pb2+ or Cd2+.
 ...
PMID:Rat kidney brush border enzyme activity following subchronic oral lead exposure. 285 32

Since streptokinase and urokinase became available for clinical use, numerous attempts have been made to improve these useful thrombolytic agents. To decrease its antigenicity, streptokinase has been fragmented or coupled to human plasminogen or polyethylene glycols. With a plasmin B chain-streptokinase complex a more potent agent was obtained. To prolong their half-life, streptokinase and urokinase were immobilized with water-soluble carriers. Coupling urokinase with fibrin-specific antibodies increases its thrombolytic efficacy, at least in vitro. The only thrombolytic agents with a relative fibrin specificity available for clinical purposes are tissue-type plasminogen activator and single chain urokinase-type plasminogen activator. Mutants and hybrids of these molecules are being constructed and may further improve their fibrin specificity and therapeutic potential.
 ...
PMID:The search for the ideal thrombolytic agent. 295 14


1 2 3 4 5 6 7 8 Next >>