Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

This study deals with the question of how blood coagulation, kallikrein and fibrinolytic systems are affected by storage of plasma at +6 degrees C. Blood was collected into citrate phosphate dextrose adenine (CPD) or acid citrate dextrose (ACD) and the plasma samples were stored at +6 degrees C for 35 days. Samples were taken at weekly intervals for assays of various parameters of the different systems. No significant changes were observed in the levels of the main thrombin inhibitor, antithrombin III. At the end of the storage period, however, fibrinopeptide A levels increased markedly, particularly in the ACD plasma, indicating thrombin activation. There was no change in the plasminogen level, but a decrease in the levels of antiplasmin and urokinase inhibitors and an increase in the level of the fibrinogen degradation fragment B beta 15-42 were observed, indicating activation of the fibrinolytic system. The level of antikallikrein activity decreased sharply in ACD plasma; CPD plasma was less affected. This decrease was parallel to the increase in spontaneous proteolytic activity and correlated with the increase in fibrinopeptide A. Prolonged storage of plasma of +6 degrees C thus resulted in the activation of coagulation, fibrinolytic and kallikrein systems and decrease in inhibitors. The activation was much more pronounced in ACD than in CPD plasma.
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PMID:Activation of blood coagulation, fibrinolytic and kallikrein systems during storage of plasma. 620 55

The rates of inhibition of high molecular weight (HMW) and low molecular weight (LMW) urokinase (UK) incubated in plasma or with purified antithrombin III (AT-III) were compared. Using a fibrinolytic assay system to determine residual biologic activity, polyacrylamide gel electrophoresis to demonstrate the formation of complexes, and selective immunoprecipitation techniques to identify the plasma inhibitors participating in the neutralization process, it was established that: (A) HMW-UK is inhibited more rapidly than LMW-UK, both in plasma and with purified AT-III; (B) heparin (3--10 U/ml accelerates the neutralization process in both systems, but only slightly; and (C) in plasma, several inhibitors, alpha 2-macroglobulin, alpha 1-antitrypsin, and antithrombin III, neutralize the activity of HMW-UK and LMW-UK.
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PMID:The inhibition of high and low molecular weight urokinase in plasma. 644 29

Dynamic fluctuations of biological activities and antigen amounts of antithrombin III (AT-III) in acute cerebrovascular diseases were analyzed and evaluated. (1) AT-III levels assayed by both biological and immunological methods showed a gradual decrease with increasing age, and levels in patients with cerebral thrombosis were lower than those in patients with cerebral hemorrhage. (2) AT-III in cerebral thrombosis decreased slowly after administration of urokinase. After administration of aspirin (acetylsalicylic acid), however, AT-III levels increased presumably due to inhibition of coagulation activities. (3) Both biological activities and antigen amounts of AT-III increased after administration of an AT-III preparation, but the measured value, especially that of biological activity, was dissociated from the expected one, due to changes of the coagulation system after an operation.
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PMID:Changes of the levels of antithrombin III in patients with cerebrovascular diseases. 663 41

It has been shown that physical exercise increases blood fibrinolytic potential, primarily by inducing a release of extrinsic plasminogen activator from the vessel wall. Synthetic estrogens have also been reported to influence fibrinolytic activity. The effect of exercise and the possible additional effect of oral contraceptive agents (OCA) on the fibronolytic system were studied in 20 competitive female rowers. Ten females used OCA (users), and 10 others did not (nonusers). All participants were subjected to standardized exhaustive exercise. Preexercise data revealed higher factor XII, total plasminogen, and free plasminogen levels together with a significantly lower C1-inactivator level in the group of users. No differences were observed in prekallikrein, high-molecular-weight kininogen, alpha 2-antiplasmin, alpha 2-macroglobulin, antithrombin III, and histidine-rich glycoprotein plasma levels. The factor XII-dependent fibrinolytic activator activity and the extrinsic (tissue-type) plasminogen activator were significantly higher; however, the urokinase-like fibrinolytic activator activity was significantly lower. These observations suggest a greater susceptibility to activation of the fibrinolytic pathways during OCA medication. Exercise resulted in a decrease of all factors under study but an increase in all fibrinolytic activities. No differences were observed between the two groups in the percentages of change that occurred with exercise.
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PMID:Effect of exercise and oral contraceptive agents on fibrinolytic potential in trained females. 672 68

The effect of orally-administered stanozolol, 5 mg b.d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and antithrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects. The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, "free" plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.
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PMID:Stanozolol-induced changes in fibrinolysis and coagulation in healthy adults. 674 May 47

We compared peritoneal dialysis effluents from 18 CAPD patients who had not suffered from peritonitis during the last 6 months (group 1) with the effluents from five patients with acute peritonitis (group 2), measuring activation markers of coagulation and fibrinolysis. These markers included prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin monomer (FM), and fibrin degradation products (FbDP). In the dialysate of group 1 we found remarkably high levels of F1 + 2, TAT and FM concomitant with a high concentration of FbDP, indicating a high rate of intraperitoneal fibrin turnover. The balance between peritoneal generation and degradation of fibrin was disturbed in untreated patients of group 2, who had significantly higher levels of coagulation markers and a higher ratio between FM and FbDP. Seven days after treatment with intraperitoneal administration of antibiotics and heparin, F1 + 2, TAT, FM and FbDP decreased significantly. To evaluate the role of mesothelial cells (MC) in the high peritoneal fibrin turnover we investigated the expression of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type-1 (PAI-1), and tissue factor in cultured human peritoneal MC under basal conditions and after exposure to tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), or bacterial lipopolysaccharide (LPS). The exposure of MC to TNF alpha or to a lesser extent IL-1 alpha or LPS reduced their fibrinolytic activity by decreasing t-PA production and increasing PAI-1 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Imbalance between intraperitoneal coagulation and fibrinolysis during peritonitis of CAPD patients: the role of mesothelial cells. 756 82

To determine whether thrombin directly modifies mobility of vascular smooth muscle cells (SMC), in Transwell systems (modified Boyden chambers), we exposed SMC to alpha-thrombin. In concentrations as low as 1 NIH U/ml, thrombin induced migration as well as proliferation of SMC. Inhibition of protein synthesis by cycloheximide (2 micrograms/ml) obviated thrombin's chemotactic effect. Neither gamma-thrombin nor D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK)-inactivated alpha-thrombin (both used as controls) exerted a chemotactic effect. Concomitant hirudin or antithrombin III plus heparin inhibited chemotaxis by thrombin when added up to 2 h after addition of thrombin. alpha-Thrombin increased SMC synthesis of urokinase receptor (uPAR) and its cell surface expression as shown by metabolic labeling and immunoprecipitation as well as by flow cytometry. Thus alpha-thrombin, in concentrations thought to be present in vivo at sites of vascular injury, can stimulate not only proliferation but also migration of vascular SMC though a mechanism(s) possibly involving synthesis of uPAR, which is known to influence migration in diverse types of cells. Accordingly, both proliferation and migration dependent on thrombin may accelerate atherosclerosis, restenosis, or both after interventions such as angioplasty.
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PMID:Vascular smooth muscle cell migration mediated by thrombin and urokinase receptor. 776 12

Intracerebral hemorrhagic transformation is one of the most important complications of thrombolytic therapy for acute ischemic stroke. The relationship between changes in markers for the coagulation and fibrinolytic systems and occurrence of hemorrhagic transformation was determined after local intra-arterial thrombolytic therapy using urokinase (UK) (24 patients) or recombinant tissue plasminogen activator (t-PA) (10 patients) within 6 hours of onset. All 34 patients had no hypodensity areas on initial computed tomography scans. Plasma concentrations of fibrinogen-fibrin degradation products (FDP), fibrinogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2 plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and D-dimer were measured. Hemorrhagic transformation occurred in seven patients (21%) with complete or partial recanalization; four in the UK group and three in the t-PA group. Doses of the thrombolytic agents did not correlate with the incidence of hemorrhagic transformation. The FDP levels in the hemorrhagic transformation group treated with UK significantly increased immediately and 1 hour after the therapy. The alpha 2-PI activities decreased and PIC levels increased in both the hemorrhagic transformation and the nonhemorrhagic groups after the therapy. The TAT levels in both groups tended to be higher than the normal range, but there was no significant difference from the pretreatment levels. The D-dimer levels in the hemorrhagic transformation group were higher than those in the nonhemorrhagic group at 24 hours after the therapy. Furthermore, the D-dimer levels were significantly higher in patients with complete recanalization compared with those with none or partial recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in coagulation and fibrinolytic system after local intra-arterial thrombolysis for acute ischemic stroke. 777 Jan 6

Heparin and heparan sulfate, exhibiting wide biological interactions, are constituted of block structures. A defined pentasaccharide motif was found responsible for the enhancement of the rate of inactivation of factor Xa by antithrombin III. Heparin also interacts with other serine proteinase inhibitors as protease nexin I, and thus possibly modulates extracellular matrix proteolysis by serine proteinases in the pericellular environment. Human neutrophil elastase (HNE) activity is inhibited by heparin with Ki = 75 pM. This strong interaction is electrostatic, involving HNE/arginine residues disposed in a "cluster shoe" arrangement on the surface of the molecule and mainly OSO3- groups of heparin. HNE-heparin interactions also interfere with HNE associations with its natural inhibitors: it decreases the rate of association of HNE with alpha 1 proteinase inhibitor (alpha 1 P(i)) by 3 orders of magnitude, while increasing kass between HNE and mucus bronchial inhibitor (MBI) by > 10 fold. In vivo experiments demonstrated that heparin fragments lacking anticoagulant activity were able to nearly completely abolish emphysematous lesions induced in mice by a single intratracheal administration of 200 micrograms HNE. Long chain unsaturated fatty acids peptide conjugates were described as competitive HNE inhibitors (Hornebeck W. et al. 1985). We synthesized N-oleoyl heparin derivative (3 oleoyl groups/one molecule of heparin); such a lipophilic glycosaminoglycan (LipoGAG), although acting as an elastin protecting agent, possessed lower HNE inhibitory capacity as compared with heparin. In contrast, however, it was able to inhibit other serine proteinases such as urokinase, plasmin, porcine pancreatic apha-chymotrypsin and elastase. Such Lipo GAG's can be therefore useful to control matrix metalloproteinases (MMPs) during tissue remodeling or tumor invasion.
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PMID:Heparin and its derivatives modulate serine proteinases (SERPS) serine proteinase inhibitors (SERPINS) balance. Physiopathological relevance. 789 38

Due to the incidence of symptomatic atherosclerosis in uremic patients, hemostasis-derived cardiovascular risk factors, basal plasma concentrations of some endothelial-derived glycoproteins and desmopressin-induced variations of endothelial-derived proteins were studied in 22 uremic patients on prolonged maintenance hemodialysis with no cardiovascular antecedent. Compared to control subjects, patients had increased predialysis hemostasis-related cardiovascular risk factors: high fibrinogen, proconvertin, and type 1 plasminogen activator inhibitor plasma concentrations; low albumin values; generally low antithrombin III values but sometimes high. They had high predialysis plasma concentrations of endothelium-derived glycoproteins: von Willebrand factor, tissue-type plasminogen activator and urokinase-type plasminogen activator, which are secreted by endothelial cells, but also soluble thrombomodulin, a marker of endothelial cell injury. The desmopressin-induced release of tissue-type plasminogen activator and of von Willebrand factor were lower than in controls. High fibrinogen, type 1 plasminogen activator inhibitor and low albumin plasma concentrations may be linked to repeated acute phase reactions associated with hemodialysis. Data concerning endothelium-related proteins are concordant with the co-existence of a chronic in vivo endothelial activation and endothelial injury in uremia. This could be linked to the initiation and progression of atherosclerosis.
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PMID:Increased cardiovascular risk factors and features of endothelial activation and dysfunction in dialyzed uremic patients. 799 2


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