Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombomodulin isolated from rabbit lung was separated by ion-exchange chromatography on DEAE-cellulose into a retarded (acidic) and a nonretarded (nonacidic) fraction. Both fractions contained the cofactor required for the activation of protein C. In addition, the acidic fraction (but not the nonacidic fraction) prevented the clotting of fibrinogen by thrombin ("direct" anticoagulant activity) and accelerated the inhibition of thrombin by antithrombin (effect corresponding to 2-10 international units of heparin per mg of protein). Both of these activities were readily neutralized by the synthetic polycation Polybrene, which did not appreciably affect protein C activation. They were also eliminated by digestion of thrombomodulin with bacterial heparinase, which, in addition, converted the acidic form of the protein C activation cofactor to a nonacidic form. Similar conversion observed during storage of thrombomodulin was attributed to endogenous proteinase activity. Density-gradient centrifugation of the acidic form of thrombomodulin in CsCl/4M guanidinium chloride failed to separate either of the direct or antithrombin-dependent anticoagulant activities from the protein C activation cofactor, which showed a buoyant density of 1.31-1.34 g/ml. The nonacidic cofactor had a lower density, 1.26-1.28 g/ml. Unreduced thrombomodulin yielded two major fractions of protein C activation cofactor on NaDodSO4/PAGE, with apparent Mr of approximately 68,000 and 57,000, respectively. The larger component contained essentially all of the direct and antithrombin-dependent anticoagulant activities. We propose that these activities as well as the negative charge and the higher buoyant density of the acidic, Mr 68,000 form of thrombomodulin are due to a heparin-like polysaccharide and, further, that this component can be separated from the major portion of the molecule, which contains the protein C activation site, through the action of a proteinase.
 ...
PMID:Functional domains of rabbit thrombomodulin. 301 29

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.
 ...
PMID:Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome. 313 21

The effect of Norplant subdermal implants on 22 different hemostatic variables was determined in 100 women attending the Fertility Control Clinic of the Singapore National University Hospital before and after 6 and 12 months of use. The factors analyzed were: hematocrit, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, fibrinogen, coagulation factor II, Factor V,Factor VII, Factor VIII, Factor VIIIR:Ag, Factor X, plasminogen activator, FDP, plasminogen (imm), antithrombin III (functional), antithrombin (antigen), protein C, alpha2-antiplasmin, alpha2-macroglobulin, alpha2-antitrypsin, platelet count, platelet aggregation (ADP), and platelet aggregation (collagen). The factors that differed significantly after 12 months were: Hb,PT,APTT, Factors II,V,VII, and VIIIR:Ag, Plasminogen (imm), antithrombin III(antigen), alpha2-antiplasmin, platelet count, and platelet aggregation. Most of these differences, while significant, were still within the normal range, except for PT,APTT, and platelet count. The subjects were considered to be in an enhanced risk for hypercoagulation and thrombosis.
 ...
PMID:The effects of Norplant-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. 314 69

We studied 30 control women and 131 pill users to evaluate effects of birth control pills and clinical factors on hemostasis. When control patients were matched with an equal number of pill users, none of the direct markers of activated hemostasis (fibrinopeptide A, platelet factor 4, and beta thromboglobulin) were increased. Plasminogen, prekallikrein, and protein C (protective against clotting) were significantly higher in pill users. Fibrinogen, antithrombin, alpha-2 antiplasmin, and fibronectin were comparable. Among the 131 pill users, antithrombin levels decreased with a family history of thromboembolism. Fibrinogen and fibronectin were increased with obesity, but there was no evidence of activated hemostasis. Overall, pill use did not appear to result in hypercoagulability. Considering family history of thromboembolism might further improve the safety of oral contraceptive use.
 ...
PMID:Oral contraceptives and the hemostatic system. 335 50

The coagulation inhibitors heparin cofactor II (HC II), antithrombin (AT) and protein C (PC) were measured in healthy term and preterm infants in order to establish reference standards. The mean value for HC II in term infants was found to be about half of the adult values. Values below 25% in healthy infants may suggest hereditary deficiency states. One girl with congenital HC II deficiency was detected. Mean AT and PC levels were somewhat higher than HC II. Healthy preterm infants have significantly lower HC II and AT values than healthy term infants. Serial AT measurements have been used in monitoring seriously ill infants and used as a prognostic indicator. In a small number of unhealthy neonates HC II was reduced to an even greater extent than AT, and on recovery normalized more rapidly than AT.
 ...
PMID:Heparin cofactor II, antithrombin and protein C in plasma from term and preterm infants. 339 3

The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the cat was examined. Cats received bolus i.v. injections of PCa of 3 micrograms/mL (n = 7), 10 micrograms/mL (n = 2) or 16 micrograms/mL (n = 1) of calculated total blood volume. Control cats (n = 7) received either unactivated Protein C (10 micrograms/mL) or the activation vehicle containing heparin and antithrombin in tris-saline buffer. Citrated blood samples were drawn prior to infusion and 5, 10, 20, 40, 60, 120 and 180 minutes post infusion. PCa caused an immediate, dose dependent increase in anticoagulation as measured by APTT which began to normalize within 20 minutes. PCa also increased fibrinolytic activity measured by euglobulin clot lysis time and an 125I whole blood clot lysis assay. However, the profibrinolytic effect of PCa did not parallel the anticoagulant effect. In all treated cats, maximum fibrinolytic activity did not occur until 40-120 minutes after infusion. Control cats demonstrated no significant change in coagulation or fibrinolytic activity. Our results demonstrate that infusion of activated human Protein C can induce anticoagulation and fibrinolytic activity in the cat.
 ...
PMID:Human protein C induces anticoagulation and increased fibrinolytic activity in the cat. 357 24

Numerous investigators have postulated that a hypercoagulable state exists in humans for a period of time before the development of thrombotic episodes. A clear biochemical definition of the prethrombotic state, however, has proved elusive due in part to the lack of reliable techniques for monitoring pertinent changes in blood coagulability. Based on recent advances in our knowledge of the biochemistry of the coagulation system, a series of highly sensitive and specific immunochemical tools has been developed that can quantitate the activities of various steps of the hemostatic mechanism in vivo at the subnanomolar level. We have established assays for F1+2 and the protein C activation peptide, which measure the cleavage of the prothrombin molecule by factor Xa and the scission of protein C by the thrombin-thrombomodulin complex, respectively. Nossel and coworkers had previously constructed similar assays for fibrinopeptide A (FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by thrombin and the proteolysis of fibrin I by plasmin, respectively. Substantial elevations in the levels of these markers have been found in patients with disseminated intravascular coagulation and many subjects with acute deep venous thrombosis. The F1+2 and FPA assays have been used to demonstrate that significant increments in factor Xa activity but not thrombin activity regularly occur in the blood of nonanticoagulated individuals with congenital deficiencies of antithrombin or protein C. These two disorders are known to be correlated with the subsequent development of thrombosis. Patients with protein C deficiency have also been noted to have significantly reduced plasma levels of protein C activation peptide. By using the immunoassays for FPA and B beta 1-42 in studies of postoperative patients, it has been shown that an imbalance between the procoagulant action of thrombin and the anticoagulant effect of plasmin on fibrin I polymer may induce an acquired thrombotic diathesis. Finally, we have recently demonstrated that prothrombin activation as measured by the F1+2 assay is suppressed by oral anticoagulants in the blood of patients with thrombotic diatheses. These investigations suggest that these assay techniques can be used to improve our understanding of the hypercoagulable state as well as to develop more effective treatment strategies for the prevention of thromboembolic events.
 ...
PMID:The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. 360 75

The coagulation inhibitors heparin cofactor II (HC II), protein C (PC) and antithrombin (AT) were measured in 14 patients undergoing uncomplicated abdominal, orthopedic or vascular surgery. Marked transient decrease of all the inhibitors was found after all surgical procedures, most prominently in vascular surgery. The greatest mean reduction was in HC II. The fall in PC and AT showed a pattern similar to that of albumin. In contrast to some earlier suggestions our results indicated that, except for HC II, the reduction probably was not due to consumption. Redistribution, hemodilution and, probably, reduced synthesis were the most important contributing factors. Serial measurements of the three coagulation inhibitors may be of prognostic value, but the present study's observed mean decrease of c. 25% in abdominal and 50-62% in vascular surgery must be borne in mind. Still lower inhibitor levels suggest consumption and a complicated postoperative course.
 ...
PMID:Plasma heparin cofactor II, protein C and antithrombin in elective surgery. 363 May 27

RIAs for hemostatic system activation were employed to study patients who were anticoagulated with warfarin. The mean prothrombin fragment F1 + 2 concentration in stably anticoagulated individuals without an inherited thrombotic diathesis (mean prothrombin time [PT] ratio [PT of patient/PT of normal plasma pool] = 1.74) was 0.231 nM as compared with a mean plasma F1 + 2 level of 1.68 nM for a nonanticoagulated control group (P less than 0.0001). The initiation of oral anticoagulants in two subjects who did not exhibit protein C deficiency led to a paradoxical increase in F1 + 2 levels during the first day of therapy. We have also shown that a relatively low intensity regimen of warfarin (PT ratio less than 1.2) may reduce elevated concentrations of F1 + 2 into the normal range in patients with a history of recurrent thromboembolism. The mean F1 + 2 level in antithrombin-deficient individuals on warfarin was significantly elevated (mean = 0.714 nM) as compared with that in anticoagulated subjects with protein C deficiency (mean = 0.205 nM) or in those without an inherited thrombotic disorder (P less than 0.01) at equivalent levels of intensity of oral anticoagulation. We therefore conclude that the effect of warfarin on hemostatic system activation is modulated by the endogenous heparan sulfate-antithrombin mechanism.
 ...
PMID:Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diatheses. 368 May 13

4 groups of 30 women participated in a study designed to examine the protein C level during late normal pregnancy, the puerperal period, and oral contraceptive (OC) use. The results were compared with those obtained with another important inhibitor, i.e., antithrombin III. In pregnant women, protein C levels during the 3rd trimester of normal pregnancy were the same as those in control nonpregnant women. Delivery did not induce any variations in protein. Antithrombin III was slightly decreased in late pregnancy, the decrease being more important at 24 hours following delivery. The women using OCs showed a significant increase in protein C compared with the control group; antithrombin was similar in both groups. The results show that protein C levels were not altered in the 3rd trimester of normal pregnancy and in the immediate postpartum period and make it difficult to assign an important role to protein C in the mechanism responsible for the increased rick of thrombosis observed in these situations. The data also eliminate the possibility that the risk of thrombosis observed in OC users could be due to a decrease in protein C.
 ...
PMID:Protein C levels in late pregnancy, postpartum and in women on oral contraceptives. 384 Dec 33


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