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)

Recently coagulopathy caused by vitamin K (VK) deficiency following antibiotic therapy in malnourished patients has been reported. We studied on the same problem particularly in patients under chemotherapy during postoperative fasting period. For this purpose, prothrombin time (PT), vitamin K-dependent coagulation factors (Factor II (F-II), VII (F-VII) and protein C), PIVKA-II (PK-II) and plasma level of VK in two groups of patients with or without VK administration were measured in esophageal cancer patients. In the group with VK, VK2 were given intravenously everyday. In the group without VK, PT prolonged and F-II decreased from the seventh postoperative day, especially on the 14th day significantly. Although F-VII and protein C decreased on the first day and returned subsequently on the seventh day, no significance was observed between two groups. PK-II increased clearly in the group without VK from the seventh day, whereas no significant changes were observed in the group with VK. The plasma level of VK1 decreased in both groups, but VK2, especially MK-4, was high in the group with VK.
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PMID:[Significance of vitamin K (VK) administration in patients under chemotherapy during postoperative fasting period]. 154 1

After a bite by the aglyphous red-necked keelback snake Rhabdophis subminiatus a complete defibrinogenation syndrome with severe hemorrhagic diathesis developed in a 25-year-old man. In vitro studies showed that the venom gland extract of the snake contains a very active prothrombin (Factor II) activator. The thrombin generated is inhibited neither by antithrombin III nor the antithrombin-III-heparin complex. The venom gland extract stimulated also the tissue plasminogen activator; however, it did not cause direct activation of plasminogen, protein C, Factor X or direct degradation of fibrinogen.
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PMID:Hemostatic changes due to the venom gland extract of the red-necked keelback snake (Rhabdophis subminiatus). 180 26

Cord blood from preeclamptic and normal gestations were analyzed for the vitamin K-dependent proteins, factors II, VII, IX, X, and protein C, and for fibrinogen and albumin. Factor II, factor IX, protein C, and albumin protein levels were reduced in the preeclamptic group, whereas there was no significant change in the fibrinogen or factor X protein levels. The data suggest that these findings are probably due to decreased synthesis and are not indicative of vitamin K deficiency.
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PMID:Hepatic impairment in fetuses of preeclamptic mothers. 232 97

Plasma levels of protein C (PC) and vitamin K-dependent coagulation factors (factors II, VII, IX and X) were measured in 100 specimens from patients on long-term warfarin therapy. Both activities and antigens of these coagulation factors were decreased, depending on the thrombotest values. Factor II activity/antigen ratio and factor X activity/antigen ratio were correlated well with thrombotest values, indicating that the concentration of inactive molecules (PIVKAs) relative to normal proteins increases with increasing intensity of anticoagulation. Although PC antigen (PC:Ag) was also decreased, the ratios between PC:Ag and vitamin K-dependent coagulation factor antigens remained constant, being independent of the intensity of warfarin therapy. These findings indicate that long-term oral anticoagulant therapy results in the suppression of the synthesis of both vitamin K-dependent coagulation factors and PC, but the production of the coagulant and anticoagulant proteins is well-balanced.
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PMID:Plasma levels of protein C and vitamin K-dependent coagulation factors in patients on long-term oral anticoagulant therapy. 377 60

The effect of human activated protein C (APC) on tissue plasminogen activator (tPA)-induced fibrinolysis was studied in cell free plasma and in a system of purified components. Clots were produced by adding plasma or a solution of fibrinogen and plasminogen to the wells of a microtiter plate containing small separated aliquots of Ca2+, thrombin, and tPA, plus and minus APC. Initial clotting and subsequent fibrinolysis were monitored continuously by turbidity. The lysis time of dialyzed normal human plasma (NHP) was longer than that of dialyzed barium citrate-adsorbed plasma (BAP). APC had no effect on the lysis time of BAP but shortened the lysis time of NHP to that of BAP. Two fractions were produced from material eluted from the barium citrate pellet by precipitation of selective components with polyethylene glycol 8000 (PEG). One fraction comprised materials which precipitated at 5% PEG (5% PF) and the other materials which precipitated between 5 and 40% PEG (5-40% PF). Both fractions together, but neither alone, prolonged the lysis time of BAP, an effect which could be reversed by APC. Fractionation of the 5% PF showed that the component with the required activity has properties of the procoagulant surface and can be replaced with vesicles of phosphatidylcholine/phosphatidylserine (PCPS). In addition, the 5-40% PF can be replaced with either the combination of purified coagulation Factors II, IX, and X or Factor II plus the prothrombin activator Factor Xa. When Factor Xa was used as the activator in BAP plus PSPC vesicles, a dose-dependent saturable increase in lysis time was observed with a half-maximal increase occurring at 32 pM Factor Xa. This effect was eliminated by APC. In a system of purified components comprising PCPS vesicles, Factors V and II, protein S, plasminogen and fibrinogen; the prothrombin activators Factor Xa and ecarin both induced a prolongation of the lysis time. APC prevented prolongation by Factor Xa but not by ecarin. The time courses of the generation of thrombin and plasmin during fibrinolysis of clots produced from systems of purified components in the presence and absence of APC, and with Factor Xa as the prothrombin activator, were determined by standardized activity assays using chromogenic substrates. In the absence of APC the lysis time was 145 min, and prothrombin was quantitatively converted to thrombin. In the presence of APC, however, the lysis time was reduced to 100 min with no evidence for the activation of prothrombin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. 847 6

Diabetic patients have increased morbidity and mortality attributable to myocardial infarction, cerebrovascular disease and peripheral vascular disease, due to a high incidence of premature atherosclerosis. Abnormalities of hemostasis have been reported in many studies on diabetes over almost thirty years, but unfortunately the results have often appeared contradictory. The hemostatic alterations could lead to increased risk of vascular disease in diabetic patients. We have studied some coagulation factors (Fibrinogen, Factor II, Factor VII) and coagulation inhibitors (Protein C, Protein S), and plasminogen in fifty-four type 2 diabetic patients. The possible relationship between coagulation factors and coagulation inhibitors and parameters for glyco-metabolic control (glycosylated hemoglobin, fructosamine) and disturbed lipid metabolism (cholesterol, triglycerides) have ben analyzed. Our results show increase of fibrinogen, correlated with the metabolic control of the disease, positive correlation between plasminogen, factor II, protein S and hypertriglycerides, decreased levels of protein C correlated neither with metabolic control of disease neither with disturbed lipid metabolism.
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PMID:[Evaluation of the coagulation and fibrinolysis system in 54 patients with type 2 diabetes mellitus: correlations with lipid metabolism and blood glucose control]. 876 54

A review is given of preparative methods for the isolation of the vitamin K-dependent clotting factors II, VII, IX, X and clotting inhibitor protein C, all derived from human plasma. Factor II, activated factor VII and activated protein C are also obtained from recombinant animal cells. The methods for their purification are described. The problem of difference in posttranslational modifications between plasma derived and recombinant protein is discussed with regard to therapeutic proteins.
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PMID:Preparation of vitamin K-dependent proteins, such as clotting factors II, VII, IX and X and clotting inhibitor protein C. 1276 31

The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1 + 2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P < 0.05) higher in the hyper- than in the hypothyroid state, whereas protein C and plasmin-antiplasmin complexes were significantly lower during the hyperthyroid period. When the 10 female patients were hyperthyroid, their levels of prothrombin fragment 1 + 2, fibrinogen, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher (P </= 0.05) than in healthy female controls, whereas when the female patients were hypothyroid, their antithrombin and plasmin-antiplasmin were lower and their protein S was higher than in controls. Factor II, plasminogen, and D-dimer were not significantly affected by the thyroid status in either assessment. In conclusion, we found evidence that the majority of patients treated with THST have a prothrombotic profile.
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PMID:Is thyroid hormone suppression therapy prothrombotic? 1535 49

Cohn Fraction IV-1 (CFIV-1) is a by-product (often discarded) of a plasma fractionation process. It retains 90% of Protein C (PC) of plasma but contains several coagulants structurally homologous to PC. Of these coagulants, Factor II (FII) has the longest half-life (12 times of PC) and largest quantity (9 times of PC) in CFIV-1. Current purification process for PC is by immunoaffinity chromatography using monoclonal antibodies, which is very expensive. Immobilized metal affinity chromatography (IMAC) is an inexpensive process that uses metal ions to adsorb proteins via their surface histidines. Affinity of PC to the metal ions in IMAC is higher than that of FII because PC has 15 surface histidines and FII has 5. Two important factors in an IMAC process are pH and imidazole concentration. PH controls protonation of histidine, and imidazole, a histidine analog, competitively reacts with metal ions. The effects of pH and imidazole on adsorption and elution of PC and FII during IMAC process were studied. The effect of pH on PC and FII adsorption was similar within the range of 6.0 and 8.0. At concentrations below 15 mM imidazole, little PC or FII eluted. At 15 and 20 mM imidazole 2.5% of PC was eluted, while 20-30% of FII was eluted.
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PMID:Effect of pH and imidazole on protein C purification from Cohn fraction IV-1 by IMAC. 1772 48

Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among healthy young adults, since only few cases were found to be carriers for the two alleles.
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PMID:Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians. 1798 31


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