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

An innovative chemically modified thrombin, succinylthrombin, was prepared by the treatment of thrombin with succinic anhydride. Succinylthrombin showed a remarkable reduction of fibrinogen clotting activity with a reduction of the potency for protein C (PC) activation. However, the degree of the remaining potency for PC activation was greater than the degree of the remaining clotting activity. The potency for PC activation was enhanced by the addition of thrombomodulin and calcium ion. The degree of the enhancement was approximately 6-times greater than that of acetylthrombin, which we previously suggested as an effective anticoagulant. The infusion of succinylthrombin into rabbits induced a prolongation of the activated partial thromboplastin time (APTT). The fibrinogen level was not affected even by the infusion of succinylthrombin of a dose which cause the prolongation of the APTT to the same extent as that following an infusion of thrombin. The factor Xa clotting time was also prolonged by the succinylthrombin without any significant drop in the number of the circulating platelet.
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PMID:Preparation of succinylthrombin and its effects in vivo on the coagulation system. 194 15

Thrombin was acetylated by treatment with acetic anhydride, and the potency for protein C activation and the fibrinogen clotting activity of the resultant acetylthrombin were investigated in vitro and in vivo. The acetylthrombin retained an amidolytic activity to the synthetic substrate, S-2238, and reduced both of the potency for protein C activation and the clotting activity. The potency for protein C activation (0.47% of that of thrombin) was retained more than the clotting activity (0.015% of that of thrombin). The enzymatic activities of acetylthrombin were in inverse proportion to the molecular weights of the substrates, S-2238, protein C, and fibrinogen. Similarly, the inhibitory activity on acetylthrombin was dependent on the molecular weights of the inhibitors, Thromstop, I-2581, hirudin, and antithrombin-III. When acetylthrombin (5000 units/kg body weight) was infused into rabbits, the activated partial thromboplastin time was prolonged to the same extent as that following infusion of thrombin (125 units/kg), but the fibrinogen level was not decreased in contrast to the large decrease following infusion of thrombin. It is suggested that acetylthrombin activates protein C without clotting fibrinogen in vivo.
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PMID:Effects of acetylthrombin on protein C activation and fibrinogen clotting. 196 50

Fifty patients presenting with acute deep-vein thrombosis were randomized in a prospective, controlled study to determine the safety and efficacy of a treatment with low-molecular-weight (LMW) heparin compared with unfractionated heparin. LMW heparin (n = 24) was administered twice daily subcutaneously at a dose of 2 X 150 anti-Xa units/kg body weight, and unfractionated heparin (n = 26) was given intravenously by continuous infusion at a dose of 450 anti-Xa units/kg body weight daily for 10 days. Doses were adjusted to maintain peak anti-Xa levels between 0.5 and 1.0 anti-Xa units per milliliter. One patient in the unfractionated heparin group and 2 patients in the LMW heparin group suffered from bleeding complications. Two patients on LMW heparin and on unfractionated heparin had high evidence of pulmonary embolism based on defects on ventilation-perfusion scintigraphy. Control phlebography and duplex sonography demonstrated a significant improvement during both treatment regimens. Reperfusion of the deep-vein system was 70% with LMW heparin and 75% with unfractionated heparin. The anti-Xa levels were significantly higher in the LMW heparin group, and activated partial thromboplastin and thrombin clotting times were significantly higher in the group receiving unfractionated heparin. Thrombin-antithrombin III complexes and D-dimer concentration decreased during the treatment, but did not differ between the two regimens. At the end of the treatment period with LMW heparin, protein C and antithrombin III were significantly higher.
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PMID:Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis. 196 63

Immunotherapy with Interleukin-2 (IL-2) and LAK cells has shown antitumoral activity in metastatic cancer patients. So far, thrombocytopenia is the major side effect reported in hemostasis. We have studied coagulation parameters in 6 patients treated with r-Met Hu IL-2 [ala-125]. In each case, we have observed a significant fall in prothrombin time, fibrinogen, protein C, anti-thrombin III, plasminogen, alpha 2-antiplasmin and all of the clotting factors except factor VIII. There was a significant increase in the activated thromboplastin time. No significant modifications of the D-Dimer test, fibrin-fibrinogen degradation products (FDP) and thrombin time were observed. Our data suggest that r-Met Hu IL-2 [ala-125] could interfere with the hepatic synthesis of the clotting factors and their inhibitors.
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PMID:Blood coagulation abnormalities during adoptive immunotherapy with interleukin-2 (r-Met Hu IL-2 [ala 125]). 200 36

In our previous paper, we reported the development of a blood collection and processing system (BCPS) suitable for the ARIC multicenter hemostasis study. As an additional step of preparation for the ARIC study, we incorporated this BCPS into an organizational plan to increase efficiency and minimize errors. We initially designed organizational trays for blood collection tubes and aliquot tubes and developed a coordinated step-by-step plan for the orderly processing of blood samples. Once the plan was considered workable, we carried out a pilot study to test the feasibility of this integrated organizational plan. Included in the pilot study were 95 healthy subjects randomly selected from 4 ARIC field centers, whose age and gender were comparable to those projected for the ARIC population. We determined the time lapse of filling the first tube as an index of blood flow. The overall mean time-lapse was 23 s (S.D. = 5). There was no significant difference among the field centers. We also determined the entire time lapse required for completing the sample processing. The total processing time was always less than 60 min. By performing the processing of samples in pairs, all the samples from two subjects could be completely processed in 70 min. This greatly increased the efficiency of field center operation. We evaluated the potential in vitro hemostasis activation by measuring plasma beta-thromboglobulin and platelet factor 4 levels. The geometric means of both proteins were comparable to our previously reported results. Fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C and activated partial thromboplastin time were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ARIC hemostasis study--II. Organizational plan and feasibility study. 208 37

The balance of coagulation and fibrinolysis was studied in 15 horses during the prodromal stages of acute laminitis induced by carbohydrate overload. Progression of the disease was stopped 12 to 24 hours before the expected onset of lameness in trial 1 (8 horses) and at the onset of lameness in trial 2 (7 horses). The end points in each trial were identified by specific changes in blood pressures (trial 1) and by changes in pulse, rectal temperature, and arterial pressure (trial 2) that were anticipated on the basis of original description of the experimental model. Blood samples for hemostasis evaluation were collected before and after carbohydrate overload in trial 1 and after carbohydrate overload in trial 2. Significant changes were not detected in platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, plasminogen concentration, alpha-2-antiplasmin, antithrombin III, protein C, thromboxane B2, or fibrin(ogen) degradation product concentration. We concluded that an imbalance in coagulation and fibrinolysis is not pathogenic in the onset of experimentally induced equine acute laminitis. Because several test methods used to evaluate hemostasis in these horses were new, reference values for 34 healthy adult horses were established.
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PMID:Evaluation of coagulation and fibrinolysis during the prodromal stages of carbohydrate-induced acute laminitis in horses. 208 21

We determined the following coagulo-fibrinolytic activities in 24 patients with systemic lupus erythematosus (SLE) and 20 healthy adults: prothrombin time (PT), activated partial thromboplastin time (A-PTT), factor VIII: coagulant activity), von Willebrand factor antigen (vWF: Ag), antithrombin-III (AT-III), plasminogen (PLG), alpha 2 plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (PIC), protein C (PC: activity and antigen concentration), and protein S (PS: total PS and free PS). PLG, AT-III, PC antigen concentration and total PS were significantly decreased in ten female controls as compared with ten male controls. Therefore, we used the ten healthy females as controls and excluded two male SLE patients in the analysis of the correlations of coagulo-fibrinolytic activities with lupus anticoagulant (LA), clinical and laboratory features in 22 female patients with SLE. In the SLE patients, PT was significantly shortened, while A-PTT was prolonged. PLG, PC activity and antigen, and total PS were significantly increased, and free PS levels were decreased in SLE. The shortened PT and decreased free PS suggest hypercoagulable states in SLE patients. A significant prolongation of A-PTT and a decrease of F VIII activity were observed in the six LA-positive SLE patients, and the results were considered as known effects of LA. Furthermore, vWF: Ag, AT-III and PC antigen levels were significantly increased in the LA-positive patients as compared with LA-negative patients. These changes indicate both vascular endothelial cell damages and a compensatory increase in coagulation inhibitors in the LA-positive patients.
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PMID:[Regulation of coagulo-fibrinolytic activity and lupus anticoagulants in systemic lupus erythematosus]. 212 31

Site-specific mutagenesis has been employed to alter the cDNA of human protein C (PC), such that the gamma-carboxyglutamic acid (gamma) pair at positions 6 and 7 of the recombinant (r) protein would be changed to aspartic acid residues. This variant, [gamma 6D, gamma 7D]r-PC, and its wild-type (wt) counterpart have been expressed in human kidney 293 cells. After purification, forms of wtr-PC that were fully gamma-carboxylated and beta-hydroxylated and of [gamma 6D, gamma 7D]r-PC that lacked only the two altered gamma-residues at amino acid sequence positions 6 and 7 were obtained. Subsequent to its conversion to activated PC (APC), [gamma 6D, gamma 7D]r-APC displayed a greatly reduced activity in the activated partial thromboplastin time of PC-deficient plasma, as compared to wtr-APC and human plasma APC. In addition, the activity of [gamma 6D, gamma 7D]r-APC toward inactivation of purified human factor VIII was reduced to less than 5% of that of wtr-APC and human plasma APC. These results, with the first reported mutations at gamma-residues of PC produced by recombinant DNA technology, indicate that the paired gamma-residues at positions 6 and 7, which are highly conserved in all vitamin K dependent coagulation proteins, are very important to generation of fully functional APC. Additional results demonstrate further that lack of gamma-carboxylation at positions 6 and 7 of PC does not substantially affect this same processing reaction at other relevant glutamic acid residues.
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PMID:A gamma-carboxyglutamic acid (gamma) variant (gamma 6D, gamma 7D) of human activated protein C displays greatly reduced activity as an anticoagulant. 212 95

The protein C activity assay of Francis and Patch (Thromb Res 1983; 32: 605-613) is based on the prolongation of the activated partial thromboplastin time in the presence of activated protein C isolated from the test samples. The assay was modified and standardized by Rapaport et al. (Am J Clin Pathol 1987; 87: 491-497), but could still only be used in patients on heparin therapy after chromatographic removal of the heparin. In this study we attempted to eliminate the heparin separation step without losing the advantages of the modified (Rapaport) method. Heparin was added to the isolated protein C to obtain a rapid and complete antithrombin effect after the thrombin activation step and polybrene was subsequently used to neutralize the excess heparin. Using this modified assay protein C activity ranged from 67 to 133% in the normal population, and from 9 to 25% in coumarin-treated patients. Precision of the modified method was acceptable in both normal and pathological PC ranges: within- and between-batch variations were 5.6 and 3.6%, and 8 and 14%, respectively. The assay correlated well (r = 0.84) with the ELISA technique in both healthy donors and non-coumarin-treated patients.
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PMID:The use of polybrene for heparin neutralization in protein C activity assay. 213 12

Although protein C (PC) and activated protein C (APC) have been postulated to be useful for treating patients with thrombosis, their critical effect remains to be studied in human subjects. To examine whether purified PC or APC are useful for treating patients with thrombosis without showing any adverse effect, we studied effects on coagulation and fibrinolysis in normal human subjects. When highly purified human PC was administered intravenously to healthy subjects, plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously administered APC decreased with a half-life of 23 min as measured by prolongation of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the plasma half-life of APC when it was measured immunologically. These findings suggested that a significant fraction of the administered APC was rapidly inhibited by plasma inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting factor VIII (F-VIII) decreased transiently as measured by clotting assay. However, when determined by a chromogenic assay method in which 120-fold diluted plasma samples were used, plasma levels of F-VIII remained unchanged. Plasma levels of F-V did not decrease after APC administration. These findings suggested that prolongation of APTT and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator inhibitor in normal subject was not affected by administration of APC. Thus, PC or APC seems to function selectively at the site of thrombin-formation without lowering plasma levels of coagulation factors.
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PMID:Effect of protein C and activated protein C on coagulation and fibrinolysis in normal human subjects. 214 Feb 5


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