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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The membrane-binding characteristics of six vitamin K dependent plasma proteins, which have homologous amino acid sequences, were compared. All of these proteins display calcium-dependent membrane binding and the identified equilibria for protein-membrane binding are qualitatively the same for all proteins. Quantitative characteristics of these protein-membrane interactions allow organization into distinct subgroups. Protein C and factor VII form a subgroup which has extemely low affinity for bilayer membranes; prothrombin, factor X, and protein S form the tightest complexes with membranes and factor IX displays intermediate affinity. In the presence of manganese (which substitutes for calcium in a cation-dependent protein transition), calcium titration of protein-membrane binding shows the same calcium dependence for all proteins except prothrombin which requires lower calcium. These protein-membrane binding characteristics agree very well with the relatedness of these proteins based on their partial amino-terminal sequences.
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PMID:Interaction of vitamin K dependent proteins with membranes. 56 56

To investigate the status of the protein C-protein S anticoagulant pathway in thalassemic patients, we measured protein C and protein S levels of plasma of 30 adults and 18 children with beta-thalassemia/HbE disease, beta-thalassemia major and HbE disease. Mean +/- 1 SD values of protein C, protein S and other coagulant proteins produced by the liver were as follows: protein C 50.4 +/- 17.2%; protein S 58.8 +/- 25.5%; antithrombin III 78.1 +/- 12.8%; PLG 86.4 +/- 18.4%; prothrombin 71.0 +/- 13.1%; factor VII 72.7 +/- 21.5%; and factor X 79.2 +/- 15.6%. Protein C and protein S levels of thalassemic patients were significantly lower than those of other coagulant proteins produced by the liver. Decrease in protein C level was stronger than that of proteins S. gamma-Carboxylated protein C levels of splenectomized patients were significantly lower than those of nonsplenectomized patients. Severe decrease of protein C and protein S may be responsible for occurrence of thrombosis in thalassemic patients.
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PMID:Protein C and protein S deficiency in thalassemic patients. 129 96

The study was aimed at an evaluation of individualized indications for antithrombotic therapy for secondary prevention in a group of 40 young survivors (aged 30-40 years) of myocardial infarction, presenting a stable phase of coronary disease. The control group consisted of 19 healthy men, of approximately similar age distribution. The determinations concerned the following: in vitro ADP and collagen induced platelet aggregation, plasma fibrinogen concentration, factor VII, VIII and antithrombin III activity, protein C concentration, spontaneous fibrinolytic activity and fibrinolytic activity after venostasis, plasminogen and alpha-2 antiplasmin activity. Moreover, to determine correlations with hemostatic parameters lipids, apolipoproteins, glucose, uric acid plasma concentration as well as percentages of lipoproteins and glycolyzed hemoglobin were also studied. In the study group various hemostasis disturbances were found: an increased platelet aggregation induced by low concentrations of ADP, increased plasma fibrinogen concentration and factor VII activity, decreased protein C concentration and impaired plasma fibrinolytic activity after venostasis. Some correlations between hemostatic and lipids parameters were also observed. Results of the study have suggested necessity for the individualized antithrombotic prevention in young survivors of myocardial infarction with antiplatelet and/or anticoagulant drugs.
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PMID:[Evaluation of thrombotic risk in young men after myocardial infarction during a period of clinical stability]. 130 May 61

The Atherosclerosis Risk in Communities (ARIC) Study is an observational epidemiologic study conducted in four communities. ARIC has two major components: One records the occurrence of myocardial infarction resulting in hospitalization and coronary heart disease death in adults aged 35 to 74 living in the communities; the other is a prospective study of representative cohorts aged 45 to 64. Measurement of hemostatic factors is part of the cohort study, whose major objectives include investigating etiologic factors associated with atherosclerosis and its clinical outcomes. Arterial intimal-medial wall thickness, an index of early atherosclerosis, is measured precisely from ultrasound images of carotid and popliteal arteries. Participants (n = 15,801) completed their first examination, which included measurements of factors associated with coagulation (fibrinogen, factor VII, factor VIII, and von Willebrand factor) and coagulation inhibition (protein C and antithrombin III). Measures of coagulation activation, platelet activation, and fibrinolytic activity will be performed on stored plasma from selected case patients and control subjects.
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PMID:The Atherosclerosis Risk in Communities (ARIC) Study. Introduction and objectives of the hemostasis component. 134 97

Several population studies have shown that plasma levels of fibrinogen and factor VII are significantly associated with ischemic cardiovascular events. However, there is little information regarding the association of hemostatic factors with early atherosclerosis. To evaluate this, we compared the plasma concentrations of several coagulation proteins (fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III) between 385 case patients, defined by high-resolution B-mode ultrasonography as having carotid arterial wall thickening, and 385 age-, race-, and sex-matched control subjects. These case patients and control subjects were selected from participants in a prospective population investigation, the Atherosclerosis Risk in Communities (ARIC) Study, who were examined between May 1987 and May 1989. Plasma fibrinogen, factor VII, protein C, and antithrombin III levels were significantly higher in case patients than in control subjects (P < 0.05). Factor VIII and von Willebrand factor were not different. These findings were supported by quartile distribution and univariate analysis. However, only fibrinogen remained significantly associated with carotid atherosclerosis on multivariate analysis taking other atherosclerosis risk factors into consideration. A one standard deviation increase in fibrinogen (67 mg/dL) was associated with a 1.6-fold increase in the odds of carotid atherosclerosis univariately (P < 0.001) and with a 1.3-fold increase in the odds multivariately (P = 0.010). Further analysis revealed that the association of fibrinogen with carotid atherosclerosis was somewhat stronger in cigarette smokers than in nonsmokers. This early case-control analysis of the ARIC Study demonstrates a significant association between plasma fibrinogen concentration and early atherosclerosis in the carotid arteries. In the context of published findings from population studies, our results indicate that plasma fibrinogen concentrations may be a useful marker for identifying individuals at high risk of developing arterial thrombotic disorders.
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PMID:Association of coagulation factors and inhibitors with carotid artery atherosclerosis. Early results of the Atherosclerosis Risk in Communities (ARIC) Study. 134 98

The relations between hemostatic variables and cardiovascular risk factors were examined in a biracial population sample of middle-aged adults. Fibrinogen, factor VII, factor VIII, von Willebrand factor, protein C, and antithrombin III levels varied considerably by age, sex, and race. Hemostatic variables also were associated with several life-style and biochemical risk factors. For the most part, higher levels of the risk factors were associated with higher levels of the hemostatic variables. The findings point to potential confounders that warrant consideration in cardiovascular disease studies, and/or mechanisms by which cardiovascular risk is conferred. They also suggest that modification of the cardiovascular risk factors may have the potential to alter the risk of thrombosis.
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PMID:Relations between hemostasis variables and cardiovascular risk factors in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators. 134 99

Recent epidemiologic studies found that there is a strong association of hemostatic factors with ischemic heart disease. The Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability (IIV) Study was conducted to estimate the various components of variation in hemostasis factors measured in the ARIC Study and to estimate the measures of repeatability of these factors. A total of 39 subjects (16 men, 23 women) were studied. Each had blood collected three times, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person (biologic) variability, and processing and assay variability were estimated. Then the reliability coefficient R was estimated as the proportion of total variance accounted for by between-person variance. The reliability coefficient can be interpreted as the correlation between measures made at repeat visits. Among the various analytes, the reliability coefficients were quite high for activated partial thromboplastin time and plasma factor VIII (R = 0.92, 0.86, respectively). Low repeatability was obtained for antithrombin III activity and protein C (R = 0.42, 0.56, respectively). The lack of repeatability for these variables derives mostly from the processing (field center and laboratory) variation. Other analytes--fibrinogen, plasma factor VII, and von Willebrand factor--were intermediate in repeatability. In comparing the analyte-specific high-level to low-level groups, no substantial difference of within-person plus method coefficient of variation between the two groups was found for any analyte except for factor VIII, whereas the corresponding variance components for most analytes were higher for the higher analyte level. Reliability coefficients from this ARIC IIV study are generally higher than those found in other studies, and this is related to the relative variations in populations studied and to the time between measurements.
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PMID:Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. 134 24

4 studies involving a combined oral contraceptive devised with norgestimate as the progestin and low-dose ethinyl estradiol as the estrogen, designed to have virtually no androgenic effects, are reviewed. A study of lipid metabolism found that cholesterol rose above desirable limits of 200 mg/dl in only 5% of women and fell within these limits in 25% who surpassed it. Similarly, triglycerides rose above 150 mg/dl in 5% with normal levels and fell in 28% who initially had high levels. 2 other studies documented increases in HDL and decreases in LDL, improving the HDL/LDL ratio. Coagulation factors were followed in a small series: no adverse effects on fibrinopeptide A, antithrombin III, protein C, Fibrinogen, factor VII, or factor VIII were seen in 6 months. No significant changes in mean levels of fasting glucose, insulin, hemoglobin A1C, or glucose tolerance were found. 2% of 2738 women developed abnormal fasting glucose levels after 6 months, while 35% lowered their initially abnormal glucose levels into the normal range after 6 months on the combined pill. Androgenicity was assessed by sex hormone binding globulin (SHBG) and free testosterone levels. The norgestimate pill elevated SHBG about 3-fold, lowering free testosterone. The prevalence of acne in norgestimate pill users is 2%. No change was noted in average blood pressure or weight. Similar results have been reported in studies on a triphasic norgestimate formulation. These results are optimistic for beneficial effects on major risk factors for cardiovascular disease, but large longterm epidemiological studies will have to be done to confirm them.
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PMID:Long-term profile of a new progestin. 136 89

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency.
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PMID:Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis. 144 May 17

Cathepsin G was used in vitro to digest human factor VII and factor IX. Clotting assays indicated that the proteinase affected a rapid loss in coagulant activity while in the presence of calcium ions the activity was almost totally protected. SDS-polyacrylamide gel electrophoresis indicated the removal of a peptide from each zymogen, VII-L from factor VII and IX-L from factor IX. This lead to the formation of VII-H and IX-H respectively. N-terminal analysis of the VII-H and IX-H products and COOH-terminal analysis of the VII-L and IX-L products confirmed that cathepsin G had cleaved position Phe40:Trp41 in factor VII and factor IX. The cleavage site is the same as that when cathepsin G is reacted with factor II, factor X and protein C. The unique action of cathepsin G may be part of a regulatory system for controlling the coagulant activity of vitamin K dependent clotting in vivo.
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PMID:Cathepsin G, a regulator of human vitamin K, dependent clotting factors and inhibitors. 144 May 18


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