Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol. Chem., in press). We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas and leukocytes, a fungal trypsin and three subtilisins. Thrombin, plasma kallikrein, factor VIIa/tissue factor and factor Xa were inhibited by BSZx at heparin independent association rates (k(ass)) of 4.5 X 10(3)-1.3 x 10(5) M(-1) s(-1) at 22 degrees C. Only factor Xa turned a significant fraction of BSZx over as substrate. Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass)=1-2 x 10(2) M(-1) s(-1)) whereas factor XIIa, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected. The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while interaction with subtilisin Carlsberg and Novo was rapid but most BSZx was cleaved as a substrate. Identification of a monoclonal antibody specific for native BSZx indicate that complex formation and loop cleavage result in similar conformational changes.
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PMID:Inhibition of coagulation factors by recombinant barley serpin BSZx. 884 56

Excessive or nonphysiologic thrombogenesis and fibrinolysis accompanies many diseases. Several specific proteins involved in the physiologic regulation and maintenance of blood in a fluid state are reviewed in this article. Assays for these proteins or evidence of their function (antithrombin III, protein C, protein S, plasminogen/plasmin, tissue plasminogen activator, plasminogen activator inhibitor I, fibrinogen/fibrin degradation products, and thrombin/antithrombin complexes) are described. Principles, general methodology, and application in veterinary medicine are discussed. Although most of the investigative work and knowledge concerning these proteins and assays has been in human beings, their use and application in veterinary medicine is becoming more available in research laboratories at referral centers and some larger commercial veterinary laboratories. Use and interpretation of these assays will help clinicians and researchers better understand pathophysiologic processes occurring in various diseases associated with thrombogenesis and excessive fibrinolysis.
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PMID:Antithrombotic and fibrinolytic factors. A review. 886 93

Studies on responses to surgical stress in blood coagulation and fibrinolysis, platelet counts and thromboxane B2 (TXB2) were carried out with 18 esophageal cancer patients who had undergone radical esophagectomy through right thoracotomy and reconstruction with gastric tube. Plasma levels were measured for the following for coagulation assessment: thrombin.antithrombin III complex (TAT), soluble fibrin monomer complex(SFMC), fibrinogen, antithrombin III, protein C and thrombomodulin. Selected fibrinolytic markers are: tissue plasminogen activator.plasminogen activator inhibitor 1 complex (tPA.PAI1C), plasminogen, alpha 2 plasmin inhibitor, plasmin. alpha 2 plasmin inhibitor complex(PIC), FDP and D-dimer. Peripheral venous blood samples were taken from the patients before the operation, immediately after the operation and on each of the first, second, third, seventh and fourteenth day after the operation. It was observed that TAT, SFMC, tPA.PAI-1C and TXB2 were remarkably altered immediately after the operation. This indicates that the major surgical stress significantly activated coagulation, fibrinolysis and platelets. Higher plasma levels of TAT compared to the pre-operation level was recorded for two weeks after the operation. Furthermore, in four cases, SFMC became positive during three to seven days after operation. These facts indicate that the activation of coagulation persisted during the days after operation. PIC began to increase from the 2nd to 3rd days after operation, reaching the maximum on the 7th day. Biphasic changes which peaked twice on the 1st and 7th days after operation were shown in plasma levels of FDP and D-dimer. These results indicate that the activation of fibrinolysis also persisted during the days after operation. The activation of coagulation and fibrinolysis may persist at least for two weeks after major surgical operation. Careful observation for the states of these systems was thought to be needed during the post-operative days, and the molecular markers could be useful to assess subclinical changes of these systems.
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PMID:[Responses to surgical stress in blood coagulation and fibrinolysis, platelet counts and thromboxane B2 after esophageal cancer operation]. 912 Oct 3

Hemodynamic forces modulate various endothelial cell functions even in the presence of cytokines under gene regulation. We have investigated the effect of shear stress on the coagulation and fibrinolysis systems in cultured human umbilical vein endothelial cells (HUVECs) perturbed by cytokines, using modified cone-plate viscometer. Thrombomodulin (TM), a surface glycoprotein receptor for thrombin that catalyzes the activation of the protein C anticoagulant pathway, and tissue factor (TF), a transmembrane glycoprotein that plays a central role in blood coagulation, are important regulators for coagulation in endothelium. Shear stress of 18 dynes/cm2 increased the expression of TM either in the presence or absence of TNF alpha (100 U/ml). In contrast, shear stresses of 6 approximately 24 dynes/cm2 decreased the expression of TNF alpha-induced TF in a shear intensity- and exposure time- dependent manner Tissue plasminogen activator(t-PA), which converts plasminogen to plasmin to degrade fibrin clot, and plasminogen activator inhibitor-1 (PAI-1), which inhibits t-PA function, play central roles in fibrinolysis in the endothelium. Treatment of the cells with IL-1 beta or TNF-alpha under static conditions had no effect on t-PA secretion, while release of PAI-1 increased. When cells were exposed to increasing shear stress up to 24 dynes/cm2, levels of t-PA significantly increased relative to shear stress, while PAI-1 secretion decreased gradually. In the presence of IL-1 beta or TNF-alpha, the increased production of t-PA was further augmented. These results clearly indicate that shear forces act as an important regulators of the coagulation and fibrinolysis systems in endothelium, to maintain antithrombogenicity of blood vessels.
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PMID:[Regulation of antithrombogenicity in endothelium by hemodynamic forces]. 913 94

Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow transplantation (BMT). Its prediction, diagnosis and treatment remain unclear. Examination was made of changes in hemostatic parameters in patients with or without VOD after BMT. Twenty-seven children were studied following BMT. Eight of them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin-antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC), antithrombin III (AT-III), protein C, N-terminal propeptide for type III procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG significantly fell during the post-transplant period (P < 0.05). Significantly low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD. The coagulation-fibrinolysis system following endothelial cell damage may contribute to the onset of VOD.
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PMID:Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation. 915 66

To investigate abnormalities in the hemostatic and fibrinolytic system in CAPD patients, parameters of coagulation, anticoagulation, fibrinolysis, and platelet function were measured in 21 CAPD patients and 20 healthy controls. The CAPD patients had significantly higher levels of factor (F) IX, FVII, FX, antithrombin III, thrombin/antithrombin III complex, protein C, protein S, thrombomodulin, fibrinogen, fibrinopeptide A, plasminogen, FXIII, alpha2-plasmin inhibitor, alpha2-plasmin inhibitor/plasmin complex, D-dimer, fibrinopeptide B beta 15-42, and beta-thromboglobin than the healthy controls. The CAPD patients also showed a shorter prothrombin time. However, tissue plasminogen activator, plasminogen activator inhibitor-1 and platelet factor-4 did not show any significant differences from the levels in healthy controls. There was a significant positive correlation between many of the blood parameters and serum lipids. These results demonstrate that hypercoagulability and secondary hyperfibrinolysis occur in CAPD patients, and suggest that these changes may be related to abnormalities in lipid metabolism.
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PMID:Hypercoagulability and secondary hyperfibrinolysis may be related to abnormal lipid metabolism in patients treated with continuous ambulatory peritoneal dialysis. 917 1

Vipera lebetina fibrinogenase (VlF) was shown to render fibrinogen incoagulable and to solubilize fibrin. The fibrinogenolytic activity of this enzyme was found to be 33 mg fibrinogen/min/mg protein. The study of the specificity of this enzyme revealed that it has no effect on purified factor X, prothrombin and protein C and on the specific chromogenic substrates of their active form. Plasminogen was not activated by VlF but slightly degraded. We have also compared the effect of VlF and plasmin on fibrinogen and shown that these two enzymes have a different sites of cleavage. This enzyme inhibited human platelet aggregation on PRP initiated by ADP and collagen but was without effect on the aggregation of washed rabbit platelets using thrombin as agonist. Administration of VlF in rat did not show any necrosis or hemorrhage in treated rats organ's. We therefore, examined the thrombolytic activity of VlF in a rat model of venous thrombosis. Thrombus was produced in the posterior vena cava by injection of human fibrinogen and thrombin. Injection of 5 mg/Kg body weight showed an evident flow restoration after one hour and measurement of the fibrinogen level a decrease of about 30% after 3 hrs. VlF's action is not dependent on plasminogen activators and may act synergistically with them, thereby providing an intriguing potential clinical application for dissolution of blood clots.
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PMID:Further characterization and thrombolytic activity in a rat model of a fibrinogenase from Vipera lebetina venom. 917 44

To find if there is a relation between levels of haemostatic variables at low and high hormonal levels (oestradiol and progesterone) in an individual, blood samples were drawn from 12 women repeatedly during one menstrual cycle (Study I) and from 14 women undergoing in vitro fertilization, before hormonal stimulation and daily during the periovulatory period (Study II). Regression coefficients were calculated between minimum (independent) and maximum (dependent) values in both studies. In Study II highly significant regression coefficients were found between oestradiol minimum (pretreatment) and maximum (median 105 and 4730 pmol/l, respectively) for coagulation factors FVIII, von Willebrand Factor (antigen), FVII (activity and antigen), fibrinogen, protein C, protein S (free), antithrombin, plasminogen and plasminogen activator inhibitor-1; furthermore, between progesterone-minimum at day -3 or -2 (related to ovum pick up) and maximum (median 4.7 and 98 nmol/l, respectively) for FVIII, von Willebrand Factor, FVII (activity and antigen), protein C, protein S (free), and plasminogen. In Study I, where much lower hormonal levels were obtained at maximum (oestradiol median 297 pmol/l and progesterone 47 nmol/l), the same pattern was observed especially for FVII, FX, fibrinogen, plasminogen and plasmin inhibitor. Thus, the concentration of a haemostatic variable at a low oestradiol or progesterone level can predict the level at a high hormonal level.
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PMID:Prediction of changes in levels of haemostatic variables during natural menstrual cycle and ovarian hyperstimulation. 918

To clarify the abnormalities of coagulation and fibrinolytic systems on predialysis patients with chronic renal failure, we measured indices of coagulation and fibrinolytic systems in 33 predialysis patients whose creatinine (Cr) levels were over 3.0 mg/dl. We termed twenty-four patients with chronic glomerulonephritis the "CGN group". We also termed nine patients wit diabetes mellitus the "DM group". We measured thrombin.antithrombin III complex (TAT), alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C, protein S, thrombomodulin (TM), vitronectin, tissue plasminogen activator.plasminogen activator inhibitor-1 complex (tPAI-C) in theses two groups. Furthermore, we measured the same indices after 6 months in the CGN group. As a result, the plasma levels of both TAT, PIC, TM/Cr ration in the DM group were significantly higher that those in the CGN group, changes in both protein S activities and plasma levels of tPAI-C were reduced significantly after 6 months. In conclusion, the abnormalities of coagulation and fibrinolytic systems in predialysis diabetic patients were stronger than those in predialysis patients with CGN. Furthermore, these abnormalities were worsened after 6 months in predialysis patients with chronic renal failure.
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PMID:[Study on coagulation fibrinolytic systems in predialysis patients with chronic renal failure--comparison between patients with chronic glomerulonephritis and patients with diabetic nephropathy]. 928 13

Pulmonary and cerebral infarctions have come to be noticed as life-threatening complications of Duchenne muscular dystrophy (DMD). In order to elucidate the underlying mechanism of hypercoagulable state, was studied following markers of coagulation and fiblinolysis in 69 DMD and 50 control patients showing no signs of thrombosis: prothrombin time, activated partial thrombin time, thrombotest, fibrinogen, fibrinogen degradation product, thrombin-antithrombin III complex (TAT), alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C activity, protein S, antithrombin III, XII factor, thrombomodulin and plasminogen activity. 66 out of 69 patients (96%) showed abnormal results in more than one of these studies, among which abnormally low thrombotest (78%), high TAT (61%) and high PIC (40.3%), were very frequently observed. The results were not correlated to the age, the activity of daily living and the respiratory of cardiac functions. Significantly smaller number of the control patients suffering from other neuromuscular diseases showed abnormal results, while the ambulatory DMD patients not infrequently showed hypercoagulable state. These results strongly suggest that unknown inherent factor(s) as well as inevitable immobilization and cardiac dysfunction play(s) an important role in the development of hypercoagulable state in this intractable disorder.
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PMID:[Hypercoagulable state in Duchenne muscular dystrophy]. 929 22


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