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)

Clinical trials have recently begun using high concentrations of activated recombinant factor VII (rFVIIa) for the treatment of hemophilic patients with inhibitors. Unexpectedly, the activated partial thromboplastin time (aPTT) was observed to be significantly shortened during infusion of the rFVIIa. To determine the mechanism for this shortening, the effect of rFVIIa on both the prothrombin time (PT) and the aPTT of normal and various factor-deficient plasmas was examined. rFVIIa shortened the PT of all plasmas tested except FX and FV deficient plasmas. rFVIIa also shortened the aPTT of all plasmas tested except FX and FV deficient plasmas. Since there is no added tissue factor (TF) in aPTT reagents, rFVIIa appeared to shorten the aPTT in the absence of TF. To investigate this possibility, the activity of rFVIIa in a purified system containing only FX, phospholipid vesicles (1:1 PS:PC), and calcium was examined. In this system, rFVIIa activated factor X in the absence of TF. If any component of the purified system was omitted, there was no detectable activation of FX. Thus it appears that calcium and phospholipids are required for the activation of FX by rFVIIa in the absence of TF. Increasing the concentration of rFVIIa increased the rate of FX activation, but the rate of activation was always much lower than that observed with even trace amounts of tissue factor. We conclude that high concentrations of rFVIIa, in the presence of calcium and phospholipid, can directly activate FX in the absence of TF and hence account for the shortening of the aPTT in inhibitor patients treated with rFVIIa.
...
PMID:Mechanism by which recombinant factor VIIa shortens the aPTT: activation of factor X in the absence of tissue factor. 262 45

It is known that antithrombin III (ATIII) activity is inhibited by tissue thromboplastin (TP) in the presence of heparin. In our study on the mechanism of the inhibition, however, TP was found to inhibit ATIII activity even in the absence of heparin, indicating an interaction between ATIII and TP. We then studied effect of ATIII on the interaction between factor VII (FVII) and TP using FVII-depleted human plasma. When the mixture of FVII + ATIII + TP was incubated at 37 degrees C and mixed with FVII-depleted plasma, the interaction between FVII and TP was inhibited. Possible complex formation was examined by electrophoretic techniques. In the immunoelectrophoresis, ATIII shifted toward the cathode in the presence of TP and the substance which had changed the mobility of ATIII showed TP activity after zone electrophoresis. The results indicated that TP had shifted toward the anode due to ATIII while ATIII had shifted toward the cathode due to TP. In the immunoblotting analysis, ATIII was separated into several bands in the presence of TP. ATIII antigenicity was altered in the presence of both heparin and TP but not in the presence of TP alone. Our results strongly suggest that TP modulates ATIII activity in the initiation of the TP-mediated coagulation cascade and that in progressing coagulation ATIII participates in the inhibition of the coagulation cascade by blocking not only thrombin activity but also the interaction between TP and FVII.
...
PMID:Interaction between human tissue thromboplastin and human antithrombin III. 263 43

Changes were explored in the behavior of circulating monocytes and their potential association with the activation of the coagulation system as assessed following strenuous exercise. Twelve men and nine women from the Norwegian national cross country skiing team and 19 men and six women from a level just below that of the national team were studied before and after ski race competition. Mononuclear cells were isolated after incubation of heparinized blood with lipopolysaccharides (LPS; 3 ng.ml-1) for 2 h. After a 50 km race for men, the specific thromboplastin activity of the stimulated monocytes rose from 3.5 x 10(-3)/10(6) cells to 21.4 x 10(-3)/10(6) cells. This probably reflects the mobilization of a new population of monocytes that are more sensitive to such stimuli. Resting top-athlete skiers had monocytes which were significantly less responsive to the LPS stimulus compared to nontrained people. There was an inverse correlation of plasma factor VII and the monocyte responsiveness to in vitro stimulation (r = 0.814; P less than 0.002) from blood drawn after a race. Furthermore, factor VII was significantly reduced after a 50 km race, and a modest decline in the fibrinogen level was also observed (P less than 0.05). It is concluded that endurance ski racing causes white cell mobilization and more active white cells that may induce activation of the coagulation system and account for the involvement of factor VII and fibrinogen.
...
PMID:Effect of strenuous exercise on blood monocytes and their relation to coagulation. 267 88

Primary nonfunction following orthotopic liver transplantation is characterized by rapidly rising serum transaminases, minimal bile production, and severe coagulopathy, which can progress to hypoglycemia, hepatic encephalopathy, and acute renal failure. Untreated it has a mortality of over 80% and to date the only treatment has been retransplantation. As a result of the beneficial effect of Prostaglandin E1 infusion in patients with fulminant hepatic failure, this trial was conducted to determine whether PGE1 would be of value in primary nonfunction. We have encountered 16 cases of primary nonfunction in 94 liver transplants, an incidence of 17%. Initially in the program, there were 6 occurrences of nonfunction that did not receive PGE1; 3 underwent retransplantation (2 survivors), 2 died awaiting another liver, and in one recovery of hepatocellular function occurred with supportive care but the patient died of cytomegalovirus infection. Ten patients received PGE1 within 4-34 hr of transplantation. Within 12 hr of treatment, 8 patients responded with a significant fall in the AST (129 U/hr) whereas, in the untreated group, the AST continued to rise (267 +/- 102 U/hr) at the same rate as prediagnosis (337 +/- 95 U/hr). At the conclusion of the infusion (4-7 days) in the 8 responders, there were significant decreases in AST (4386 +/- 546 U/L to 102 +/- 21 U/L), prothrombin time (22 +/- 2 to 12 +/- .4 sec) and partial thromboplastin time (45 +/- 3-29 +/- 4 sec), and significant increases in coagulation factor V (26 +/- 8 to 95 +/- 12%) and factor VII (10 +/- 5 to 61 +/- 4%). No serious side effects occurred, although 2 patients developed diarrhea, and abdominal cramps. Two patients treated with PGE1 were retransplanted at 10-36 hr and were considered nonresponders. Graft survival was 80% in the PGE1-treated group and 17% in the untreated group (P less than 0.05) and patient survival was 90% and 33%, respectively. This study suggests a potential benefit of PGE1 in the treatment of primary nonfunction.
...
PMID:Treatment of primary liver graft nonfunction with prostaglandin E1. 267 5

Glutamylglycinylarginyl chloromethyl ketone, tyrosylglycinylarginyl chloromethyl ketone, and phenylalanylprolylarginyl chloromethyl ketone have been labeled at their amino termini using fluorescein, rhodamine-X, lissamine-rhodamine, pyrene, and the 1,5-, 2,5-, and 2,6-dimethylaminonaphthalene-1-sulfonyl moieties. These peptidyl chloromethyl ketones have also been modified by incorporation of biotin and epsilon-amino caproyl biotin. The ability of these various chloromethyl ketones to be incorporated into a collection of zymogen-enzyme pairs has been evaluated using a variety of coagulation and fibrinolytic proteins. All labeled chloromethyl ketones were efficiently incorporated into the proteases tested, with the exception of urokinase which was refractory to inhibition by phenylalanylprolylarginyl chloromethyl ketone derivatives. No modification of any zymogen species was observed even under conditions designed to detect minimal reactivity. When enzymes were modified using chloromethyl ketones labeled with epsilon-amino caproyl biotin, the modified proteins readily reacted with avidin under a variety of different conditions. The observed reactivity with avidin was used in enzyme "blotting" following electrophoretic resolution of polypeptide chains and to remove active enzyme present in enzyme-zymogen mixtures. These reagents have been used to evaluate the potential for active site expression by the single-chain human factor VII molecule. Studies conducted with tissue factor, phospholipids, and calcium using factor X as substrate demonstrate that no activity can be obtained without initial activation of either factor X to factor Xa or factor VII to factor VIIa by an external source. We thus conclude that factor VII is a true zymogen, inert in the blood clotting process prior to its cleavage to factor VIIa.
...
PMID:Zymogen/enzyme discrimination using peptide chloromethyl ketones. 270 77

The procoagulant activity (PCA) of disrupted monocytes was examined in 32 diabetic patients (26 with insulin-dependent and 6 with non-insulin-dependent diabetes) versus 30 control subjects. Diabetes monocytes exhibited a weak PCA before any incubation, associated in 10 cases with a significant amount of factor VII activity. Incubation led to a significant rise in PCA in diabetes cells, when stimulated with lipopolysaccharide or not, and in control cells only after stimulation. In incubated diabetes cells, PCA was prothrombinase-like when factor VII was associated with the freshly isolated cells, and tissue factor-like (as in the controls) when no factor VII was associated with the cells. The characteristics of PCA were not correlated with clinical features or with the type of diabetes. Our study suggests that diabetes monocytes exhibit a higher level of PCA than control ones, possibly corresponding to an in vivo stimulation, or at least a higher responsiveness to stimuli occurring in vitro.
...
PMID:Distinctive features of procoagulant response of monocytes from diabetic patients. 273 77

The synergistic effect of antithrombin III (ATIII), activated protein C (APC) and heparin on the tissue thromboplastin (TP)-mediated coagulation cascade was studied. APC prolonged the activated partial thromboplastin time of human plasma with increasing APC concentration but affected the prothrombin time only slightly. Neither ATIII nor heparin prolonged the prothrombin time by itself, while a mixture of APC and heparin strongly inhibited the coagulation. When the effects of APC, heparin and ATIII on the TP-mediated coagulation were examined with a solution consisting of prothrombin, factor V, factor VII, factor X and fibrinogen at physiological concentrations, the coagulation time was prolonged only slightly by the APC-heparin or ATIII-heparin mixture. However, the coagulation time was prolonged markedly by simultaneous addition of APC, ATIII and heparin to the solution. Inhibition of thrombin activity by the ATIII-APC-heparin mixture was weak as compared with that by the ATIII-heparin mixture after a 1-min incubation, but after a 2-min incubation the inhibitory activities were equal. Suppression of thrombin activity by the ATIII-APC-heparin mixture was supposed to be due to the inhibition of the interaction between ATIII and heparin on thrombin by APC because the APC-ATIII-heparin complex was detected by crossed immuno-electrophoresis but not by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. When the inhibitory effect of APC alone or the APC-heparin mixture on the platelet prothrombin converting activity (PPCA) was examined, heparin accelerated the PPCA inhibition by APC.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Synergistic effect of antithrombin III, activated protein C and heparin on the inhibition of the tissue thromboplastin-mediated coagulation. 275 79

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
...
PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

The effect of a synthetic pentasaccharide that specifically causes the inactivation of factor Xa on the development of prothrombinase activity in human plasma was monitored using four triggers of coagulation: (a) human brain thromboplastin; (b) contact activation; (c) factor X activating enzyme complex; (d) prothrombin activating enzyme complex. Inhibition was similar with the triggers a, b and c. With prothrombinase (d), the inhibition strongly decreased with increasing amounts of factor Va present. This indicates that only free factor Xa is inhibited. Because both the intrinsic pathway (b) and the extrinsic pathway (a) are inhibited by the pentasaccharide, we conclude that free factor Xa plays a rate-limiting role in the pathways, so that there is no reason to postulate the existence of 'supercomplexes' consisting of factors IXa, VIIIa, X(a), Va and prothrombin adsorbed on the same phospholipid particle (intrinsic system) or factor VII(a), X(a), Va and prothrombin adsorbed on tissue thromboplastin (extrinsic system).
...
PMID:Free factor Xa is on the main pathway of thrombin generation in clotting plasma. 277 96

Lipoprotein-Associated Coagulation Inhibitor (LACI) is a factor Xa dependent inhibitor of the factor VII(a)/Tissue Factor catalytic complex. Deduced from partial cDNA sequence, LACI's amino acid sequence has recently been reported. Northern blot analysis showed LACI cDNA hybridizes to RNAs of 1.4 and 4.0 kb in size. To complete the characterization of the LACI message(s), overlapping LACI cDNAs were isolated from a human endothelial cell library. Sequence analysis revealed the clones' inserts span 4023 bases of sequence, consisting of 381 bases of 5' untranslated sequence, an open reading frame of 912 bases, 2682 bases of 3' untranslated sequence and 48 bases of poly(A) sequence. In addition, a short 1.4 kb insert which encodes for LACI was found to contain 49 bases of 3' untranslated sequence and a 3' poly(A) tail. The 1.4 kb of sequence is contained in the 4.0 kb sequence, except for 14 bases of 5' sequence, suggesting that the LACI messages arise by the use of alternative termination and polyadenylation signals during processing. Northern blot analysis of RNA isolated from cells treated with actinomycin D showed both RNA species appear to be relatively stable. Using a bovine papilloma virus vector, LACI cDNA was transfected into mouse C127 fibroblasts. The recombinant LACI is recognized by polyclonal anti-LACI IgG, binds to factor Xa and inhibits VII(a)/Tissue Factor activity in a similar fashion as LACI purified from HepG2 cell conditioned media.
...
PMID:Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein. 278 20


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

---