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

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model of Protein C (PC) activation in vivo was used to investigate the complexing of activated PC (APC) with its plasma inhibitors, PC inhibitor (PCI) and alpha 1-antitrypsin (alpha 1AT). Chimpanzees were infused with a bolus of activated factor X (F.Xa) together with vesicles of phosphatidylcholine and phosphatidylserine (PCPS). Pre- and post-infusion plasma samples were analyzed using enzyme linked immunosorbent based assays (ELISA) for PC and APC complexes, and immunoblotting of PC from nondenaturing polyacrylamide gel electrophoresis. Within 2 minutes of infusion, a 60% decrease in nonactivated PC zymogen (PCz) levels was observed. This coincided with a precipitous drop in plasma activities of cofactors VIIIa and Va. In contrast, total PC antigen (PCt) levels decreased by only 1%, indicating APC generation. Complexes of APC with both PCI and alpha 1AT were observed on immunoblots, and further identified and quantified using a sandwich ELISA employing antibodies to both PC and these inhibitors. The distribution of APC between these two inhibitors varied with the dose of F.Xa/PCPS infused. At a dose of F.Xa/PCPS of 24.05 pmol and 37.70 nmol/kg, respectively, an initial spike of APC generation, associated with decreases in the levels of factors VIIIa and Va, was noted but dissipated over the next 30 minutes. During this period, APC/inhibitor complexes appeared with the levels of APC-PCI and APC-alpha 1AT reaching 8.5 nmol/L and 2.2 nmol/L by 30 minutes, respectively. In contrast, at a higher dose of F.Xa/PCPS of 36.60 pmol and 56.30 nmol/Kg respectively, complexes of APC-alpha 1AT appeared rapidly and reached a level of 6 nmol/L by 30 minutes postinfusion, whereas APC-PCI complexes were only present at a concentration of 3.4 nmol/L by this time. Additional experiments with lower doses of F.Xa/PCPS suggest that PCI is the preferred inhibitor of APC, but as the availability of this inhibitor becomes limiting, alpha 1AT plays an increasingly crucial role as a secondary inhibitor of endogenously generated APC. Moreover, evidence is presented suggesting the existence of additional inhibitor(s) of APC that may have a role similar to alpha 1AT.
...
PMID:A qualitative and quantitative analysis of the activation and inactivation of protein C in vivo in a primate model. 234 80

A family with inherited combined deficiency of factor V and von Willebrand factor (vWF) is reported. Hematological examination of 41 year-old female proband and her younger brother revealed prolonged prothrombin time and Kaolin partial thromboplastin time. The level of both factor V activity and factor V antigen markedly decreased, below 15% of normal. The decreased levels of factor VIII activity and vWF activity are also seen. Furthermore, abnormal mobilities were observed in crossed immunoelectrophoresis. The protein C, S antigens and activities, and protein C inhibitor activity were within normal. Four sons have received the 50% levels of factor V from their parents. One of them also showed the 50% of factor VIII and vWF activities. From above results, this family is thought to be a case of inherited deficiency of factor V and vWF, which are transmitted as an autosomal trait apparently.
...
PMID:[A family of congenital combined deficiency of factor V and von Willebrand factor]. 236 42

To determine whether children treated with chronic peritoneal dialysis have a hypercoagulable state, various coagulation and fibrinolytic factor concentrations or activities were measured in 17 children undergoing chronic peritoneal dialysis. The patients had significantly increased activities of factors VII and VIII, and increased concentrations of von Willebrand factor (vWF), fibrinogen, factor XIIIA and factor XIIIS compared to reference values (P less than 0.001 in each case). The activated partial thromboplastin time was prolonged (P less than 0.001) and the thrombin clotting time was decreased (P less than 0.05) in these children. The prothrombin time and activities of factors XII, XI, IX, X, V and II were not significantly different from control values. Protein C concentrations were similar to normal, but antithrombin III concentrations were increased (P less than 0.05). Within the fibrinolytic pathway, decreased concentrations of plasminogen were found (P less than 0.001) and the concentrations of alpha-2-antiplasmin were increased (P less than 0.001). The plasma albumin concentration was below 33 g/l in 13 of the 17 children. The duration of treatment with peritoneal dialysis was directly correlated with vWF concentrations (P less than 0.001) and inversely correlated with factor VII concentrations (P less than 0.01). Of these patients 2 have since had clinical thrombotic episodes. The coagulation abnormalities found may have a role in the occurrence of thrombosis complicating renal transplantation.
...
PMID:Coagulation abnormalities in chronic peritoneal dialysis. 239 81

Parameters of the fibrinolytic system were studied in a primate model where the generation of thrombin was promoted in vivo. The procoagulant stimulus used was a combination of human factor Xa in combination with phosphatidylcholine/phosphatidylserine lipid vesicles (PCPS) as the source of coagulant active phospholipid. The dosage of each component was formulated to provide a gradation of thrombin generating potential assessed prior to in vivo study in an in vitro clotting assay. These ranged from 25.25-36.60 pMole/kg (factor Xa) and 18.85-56.30 nMole/kg (PCPS). In each case, the ratio of the dose of factor Xa/PCPS was maintained at 0.65 (pMole factor Xa/nMole PCPS). Individual dosage combinations producing recalcification clotting times in vitro of 15, 20, 25 and 30 s were used in detailed in vivo studies. Previous studies in dogs had confirmed the thrombin generating potential of factor Xa/PCPS infusions and demonstrated an associated activation of protein C and increased fibrinolytic activity. This has now been extensively characterized in the chimpanzee as follows: 10 min after the infusion of the highest dose (36.6 pMole factor Xa/56.3 nMole PCPS kg bodyweight), the level of circulating t-PA had risen to 900 ng/ml (antigen), 885 IU/ml (functional). Dosage was observed with the lowest dose of 12.25 pMole factor Xa and 18.85 nMole PCPS being associated with relatively minor increases in circulating t-PA activity. There were no changes in u-PA at any dosage during the full time course of the experimental period (90 min). Plasminogen activation was also apparent with alpha-2 antiplasmin levels falling to 30-40% of pre-infusion levels at the highest dosages.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The fibrinolytic potential of the normal primate following the generation of thrombin in vivo. 240 50

The plasma proteinase inhibitors are relatively ineffective in the inhibition of the activity of the platelet prothrombinase complex, due to the low rates of inhibition, and possibly due to the indirect protection from the potentiating effect of the vascular endothelium. The plasma proteinase inhibitors are more effective at inhibiting thrombin, thereby preventing the feedback activation of platelets and factor V and subsequent prothrombinase complex development. This may constitute a mechanism for the control of the development of the prothrombinase complex on the platelet surface. The protein C-thrombomodulin mechanism for the destruction of factor Va activity probably constitutes a major inhibitory mechanism for the prothrombinase complex in vivo.
...
PMID:Mechanisms of inhibition of platelet coagulant activity. 242 87

The protein C activator Protac from A. contortrix venom is being investigated as a potential antithrombotic agent and as a tool for the preparation of activated protein C. Its established major application is the zymogen activation in functional protein C determinations based on either a clotting assay or a chromogenic substrate technique. The sensitivity of the activated partial thromboplastin time as an indicator reaction for Protac activated protein C depends on the contact activator component of the reagent. Protein C dose-response increased in the following order: kaolin greater than ellagic acid greater than sulfatide. This phenomenon is due to a competition of molecular affinities between Protac, plasma components and the different activating surfaces.
...
PMID:Practical application of the protein C activator Protac from Agkistrodon contortrix venom. 246 12

The activation of protein C by thrombin is thought to occur at the endothelial cell surface in the presence of an essential membrane glycoprotein cofactor, thrombomodulin. In the present study it is demonstrated that, in the presence of hirudin, the most potent known inhibitor of thrombin, human protein C can be activated by human factor Xa (20 nM), but by a thrombomodulin-independent mechanism requiring only the presence of Ca2+ and phospholipid vesicles bearing a high proportion of negative charges (30-75% phosphatidylserine, depending on the conditions). At an optimal concentration of phosphatidylserine/phosphatidylcholine (1:1, w/w) of 75 microM, the apparent Km was 1 microM with a kcat. of 1 min-1. At 25 microM-phospholipid the Km was unchanged and the kcat. was 0.67 min-1. At either lipid concentration, increasing the density of negative charges by the adjunction of sulphated polysaccharides, like pentosan polysulphate or standard heparin at optimal concentrations of 2-5 micrograms/ml and 5-10 micrograms/ml respectively, resulted in a 4-fold increase of the kcat. without affecting the Km. Sulphated polysaccharides alone were poor promoters of protein C activation by factor Xa. In any case the presence of Ca2+ was essential, the dependence being sigmoidal with Hill coefficients ranging from 1.4 to 2.0. No significant activation of 4-carboxyglutamic acid-domainless protein C, a chymotrypic derivative lacking the phospholipid-binding domain, could be detected in the presence of phospholipids and Ca2+, with or without pentosan polysulphate. In a large molar excess, other phospholipid-binding entities like prothrombin fragments F1 or F1+2 could inhibit protein C activation by factor Xa, but pentosan polysulphate exerted a clear protective effect. Factor Xa irreversibly inhibited at its active centre, but not di-isopropyl phosphoro-thrombin, behaved as an inhibitor but in a more complex manner than simple Michaelis-Menten kinetics. Among several derivatives of pentosan polysulphate or of heparin which were tested, those having the higher degree of sulphation and/or molecular mass were the most efficient in enhancing the rate of activation of protein C by factor Xa in the presence of phospholipids. These results suggest that human factor Xa, at physiological concentrations, could activate human protein C in the presence of anionic phospholipids and that this activation could be potentiated by therapeutic concentrations of sulphated polysaccharides.
...
PMID:Activation of human protein C by blood coagulation factor Xa in the presence of anionic phospholipids. Enhancement by sulphated polysaccharides. 247 15

Lupus-like anticoagulants (LLA), lupus anticoagulant and/or anticardiolipin antibody, are increasingly recognized in association with venous and arterial thrombotic events. We recently reviewed our experience with patients undergoing revascularization for lower-limb ischemia who were found to have LLA. Nine patients had LLA based on a prolongation of the partial thromboplastin time or by anticardiolipin assay by an enzyme-linked immunosorbent assay system. The ages of the patients ranged from 23 to 57 years. There were seven (78%) men, six (67%) blacks, two (22%) diabetic patients, and three (33%) hypertensive patients. One patient had systemic lupus erythematosus. All patients except one were cigarette smokers. Four patients had concurrent regulatory protein abnormalities: three protein C deficiencies, one protein S deficiency, and one plasminogen deficiency. The nine patients had 10 lower-extremity arterial reconstructions with two postoperative failures within 30 days. Patients were anticoagulated with heparin or aspirin after all but one operation. Patients at risk were identified on the basis of age (less than 51 years), unexplained early graft thrombosis, or history of venous or arterial thrombotic events. This group of patients is believed to be at risk for early postoperative thrombosis. Postoperative anticoagulation after revascularization for patients with LLA may be beneficial.
...
PMID:Lupus-like anticoagulants and lower extremity arterial occlusive disease. 250 7

A group of leupeptin analogues was found in Streptomyces griseus strain 254, isolated from a soil sample from Fujian Province, China. The inhibitors excreted in the culture filtrate were purified by adsorption on macroporous resin, followed by sequential ion exchange chromatography on DEAE-52 cellulose, CM-32 cellulose and affinity chromatography with immobilized trypsin. The preparation thus obtained was further purified by preparative HPLC. Several major components were found and characterized, which possessed different inhibitory properties toward trypsin. Based upon amino acid and mass spectrophotometric analysis, these peptides were placed in four major structural categories, viz., R-Val-Val-argininal, R-Leu-Leu-argininal, R-Ile-Ile-argininal and R-Thr-Thr-argininal, this latter component representing a newly identified leupeptin analogue. The structural variability of the R-group was partly responsible for the multiplicity of the peaks obtained with HPLC. All peptides displayed varying degrees of inhibitory activity toward proteases involved in blood coagulation and fibrinolysis, including plasmin, factor Xa, activated protein C and thrombin. Among these peptide inhibitors, the molecule containing threonine showed the strongest inhibitory activity.
...
PMID:The inhibition of the enzymic activity of blood coagulation and fibrinolytic serine proteases by a new leupeptin-like inhibitor, and its structural analogues, isolated from Streptomyces griseus. 250 6

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.
...
PMID:The quantitative association of plasma endotoxin, antithrombin, protein C, extrinsic pathway inhibitor and fibrinopeptide A in systemic meningococcal disease. 251 Mar 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---