The Experts below are selected from a list of 23541 Experts worldwide ranked by ideXlab platform
Kenneth A. Bauer - One of the best experts on this subject based on the ideXlab platform.
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Recombinant Factor VIIa for the treatment of congenital Factor VII deficiency.
Seminars in thrombosis and hemostasis, 2000Co-Authors: Mathilde Hunault, Kenneth A. BauerAbstract:Factor VII deficiency is a rare autosomal bleeding disorder with a highly variable hemorrhagic predisposition. Severe bleeding, including hemarthroses, may be encountered when plasma Factor VII levels are below 1%. Patients have prolonged prothrombin times, and the final diagnosis is established by quantitative Factor VII assays. Some patients have true deficiencies, that is, very low Factor VII activity and low Factor VII antigen (cross-reacting material) levels (CRM-); others have normal antigen levels but low activity (CRM + ). Still others have reduced antigen levels (CRM R ). There is a rather poor correlation between clinical symptoms and Factor VII activity levels in plasma. Treatment of these patients consists of fresh frozen plasma, prothrombin complex concentrates, or Factor VII concentrates. Recombinant activated Factor VII (rFVIIa) is a very useful alternative, and several patients have been treated successfully. Because of the short half-life of Factor VIIa, repeated doses have to be administered, and continuous infusion may be even better. Antibodies to Factor VII have been reported but seem to be rather rare. From the available data it appears that rFVIIa is a safe and effective treatment modality for patients with congenital Factor VII deficiency.
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Severe Factor VII Deficiency Due to a Mutation Disrupting an Sp1 Binding Site in the Factor VII Promoter
Blood, 1998Co-Authors: Josephine A. Carew, Eleanor S. Pollak, Katherine A. High, Kenneth A. BauerAbstract:We have identified a point mutation in the promoter of the Factor VII gene responsible for a severe bleeding disorder in a patient from a large French-Canadian family with known consanguinity. The proband has an extremely low plasma level of Factor VII antigen and Factor VII coagulant activity (<1 percent of normal) and suffers from hemarthroses and chronic arthropathy. Sequencing of the patient’s Factor VII 5′ flanking region, intron/exon junctions, and coding regions showed a homozygous point mutation, a C to G transversion at position −94 relative to the translation start site. We show here that this mutation prevented binding of transcription Factor Sp1 and of other nuclear proteins to this region of the Factor VII promoter and resulted in a 20-fold reduction in reporter gene expression in HepG2 cells. These data underscore the importance of this region of the Factor VII promoter for in vivo expression of the Factor VII gene.© 1998 by The American Society of Hematology.
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Severe Factor VII Deficiency Due to a Mutation Disrupting an Sp1 Binding Site in the Factor VII Promoter
Blood, 1998Co-Authors: Josephine A. Carew, Eleanor S. Pollak, Katherine A. High, Kenneth A. BauerAbstract:We have identified a point mutation in the promoter of the Factor VII gene responsible for a severe bleeding disorder in a patient from a large French-Canadian family with known consanguinity. The proband has an extremely low plasma level of Factor VII antigen and Factor VII coagulant activity (
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Severe Factor VII deficiency due to a mutation disrupting a hepatocyte nuclear Factor 4 binding site in the Factor VII promoter.
Blood, 1997Co-Authors: Arnaldo A. Arbini, Eleanor S. Pollak, Katherine A. High, Janet K. Bayleran, Kenneth A. BauerAbstract:Although small deletions, splice site abnormalities, missense, and nonsense mutations have been identified in patients with Factor VII deficiency, there have been no reports of mutations in the Factor VII promoter. We investigated a girl with Factor VII levels that were less than 1% of normal in association with a severe bleeding diathesis. The patient is homozygous for a T to G transversion that occurs 61 bp before the translation start site. This nucleotide is in a sequence that is an hepatocyte nuclear Factor 4 (HNF-4) binding site within the Factor VII promoter (ACTTTG AE → ACGTTG). Using gel mobility shift assays, we show that the mutation disrupts the binding of HNF-4 to its cognate binding site. In growth hormone reporter gene assays, the activity of a plasmid containing the mutant promoter was 6.7% of the wild-type promoter plasmid. Although HNF-4 was able to transactivate the wild-type Factor VII promoter 5.4-fold in HeLa cells, no transactivation could be shown with the mutant promoter. These findings indicate that HNF-4 exerts a major positive regulatory effect on Factor VII expression and provides in vivo evidence that binding of this transcription Factor is critical for normal Factor VII expression.
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Severe Factor VII Deficiency Due to a Mutation Disrupting a Hepatocyte Nuclear Factor 4 Binding Site in the Factor VII Promoter
Blood, 1997Co-Authors: Arnaldo A. Arbini, Eleanor S. Pollak, Katherine A. High, Janet K. Bayleran, Kenneth A. BauerAbstract:Although small deletions, splice site abnormalities, missense, and nonsense mutations have been identified in patients with Factor VII deficiency, there have been no reports of mutations in the Factor VII promoter. We investigated a girl with Factor VII levels that were less than 1% of normal in association with a severe bleeding diathesis. The patient is homozygous for a T to G transversion that occurs 61 bp before the translation start site. This nucleotide is in a sequence that is an hepatocyte nuclear Factor 4 (HNF-4) binding site within the Factor VII promoter (ACTTTG Æ → ACGTTG). Using gel mobility shift assays, we show that the mutation disrupts the binding of HNF-4 to its cognate binding site. In growth hormone reporter gene assays, the activity of a plasmid containing the mutant promoter was 6.7% of the wild-type promoter plasmid. Although HNF-4 was able to transactivate the wild-type Factor VII promoter 5.4-fold in HeLa cells, no transactivation could be shown with the mutant promoter. These findings indicate that HNF-4 exerts a major positive regulatory effect on Factor VII expression and provides in vivo evidence that binding of this transcription Factor is critical for normal Factor VII expression.
Anders Hamsten - One of the best experts on this subject based on the ideXlab platform.
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Elevated levels of Factor VII activity in the postprandial state: effect of the Factor VII Arg-Gln polymorphism.
Thrombosis and haemostasis, 1994Co-Authors: Angela Silveira, Fiona Green, Fredrik Karpe, Margareta Blombäck, Steve E. Humphries, Anders HamstenAbstract:A genetic polymorphism (Arg/Gln353) of coagulation Factor VII was recently identified and shown to be associated with differences in basal Factor VII coagulant activity. Postprandial lipaemia seems to exert an acute but evanescent effect on the activity of Factor VII, and the influence of the Arg/Gln353 polymorphism on Factor VII activation during postprandial lipaemia was therefore studied in male post-infarction patients [age 48.8 +/- 3.3 years (mean +/- SD)] with Arg/Arg (n = 23) and Arg/Gln (n = 8) genotypes. Factor VII antigen (VIIag) and activity along with plasma lipoproteins were determined before and after intake of a mixed meal-type of oral fat load. Patients with the Arg/Gln genotype had basal VIIag and activated Factor VII (VIIa) levels 75% and 48%, respectively, of those of patients homozygous for the Arg allele. In absolute terms, VIIa increased more in homozygotes for the Arg allele (delta 0-6 h VIIa 1.76 +/- 1.48 ng/ml) than in heterozygotes (0.60 +/- 0.27 ng/ml) in response to fat intake, but the percentage increase in VIIa molecules did not differ significantly between subjects with Arg/Arg and Arg/Gln genotypes (37 +/- 32% versus 27 +/- 15%). This suggests that the influence of the Arg/Gln polymorphism on Factor VII activity is mainly accounted for by differences in the basal Factor VII protein level between genotypes. Since most of our lives are spent in the postprandial state, possession of the Factor VII-Gln353 allele is likely to confer protection against coronary heart disease by reducing the amount of VIIa produced in response to fat intake.
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Activation of coagulation Factor VII during alimentary lipemia.
Arteriosclerosis and thrombosis : a journal of vascular biology, 1994Co-Authors: Angela Silveira, Fredrik Karpe, Margareta Blombäck, George Steiner, Göran Walldius, Anders HamstenAbstract:Dietary studies have established a connection between plasma lipoproteins and coagulation Factor VII. The present study was undertaken to specifically examine whether Factor VII is activated during alimentary lipemia and to investigate the relations of Factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for Factor VII determination was used to ensure that changes in all potentially existing forms of the Factor during alimentary lipemia would be included. Substantial activation of Factor VII was found to occur during alimentary lipemia, whereas the number of Factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of Factor VII was more pronounced in control subjects than patients, and the proportion of activated Factor VII molecules was higher in control subjects. Interestingly, Factor VII activation, which correlated quantitatively with the degree of postprandial triglyceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why Factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation Factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.
Ulf De Faire - One of the best experts on this subject based on the ideXlab platform.
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Genetic effects for plasma Factor VII levels independent of and in common with triglycerides.
Thrombosis and Haemostasis, 1999Co-Authors: Yuling Hong, Nils Egberg, Nancy L Pedersen, Ulf De FaireAbstract:Background. Coagulation Factor VII has been demonstrated as a potential risk Factor for cardiovascular disease. Both genes and non-genetic Factors are related to plasma levels of Factor VII. However, the extent to which genetic effects influence variability in plasma Factor VII levels is unknown. Further, increased levels of plasma Factor VII are associated with serum triglycerides, yet the reason for this association is not fully understood. Methods and Results. Quantitative genetic analyses were applied to evaluate the relative importance of genetic and different environmental influences on plasma Factor VII levels and to test the significance of genetic and environmental Factors in common to Factor VII and triglycerides in 215 pairs of middle-aged and elderly twins, of whom 104 were reared apart and 120 were women. Genetic influences were found to account for 57% of the individual differences in plasma Factor VII levels, whereas shared-rearing and residual-familial environmental Factors were not significant. Furthermore, a significant genetic correlation of 0.38 was found between Factor VII and triglycerides, but the environmental correlation between these two measures was not significant. Genetic Factors in common to Factor VII and triglycerides explain about 7% of the total variance for Factor VII. Conclusion. The present study suggests that there are substantial genetic influences on plasma Factor VII levels. Furthermore, genetic effects explain the phenotypic association between Factor VII and triglycerides.
Giovanni Bonadonna - One of the best experts on this subject based on the ideXlab platform.
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Levels of plasma Factor VII and Factor VII activated forms as a function of plasma triglyceride levels
Atherosclerosis, 1993Co-Authors: Mauro Negria, Pasquale Luigi Arigliano, Giorgio Talamini, Stefano Carlinia, Franco Manzato, Giovanni BonadonnaAbstract:Abstract It has been shown that triglyceride levels are one of the determinants of Factor VII levels. In this study we have simultaneously evaluated, in a group of 102 healthy individuals, the different forms of Factor VII, namely Factor VII mass, Factor VII coagulant activity, activated Factor VII double-chain form and Factor VII-phospholipid complex, in relation to triglyceridaemia. The data showed a highly significant correlation of Factor VII mass, Factor VII coagulant activity and Factor VII-phospholipid complex with triglycerides. No correlation was observed between the activated Factor VII double-chain form and triglycerides. These data, together with analysis of the linear and orthogonal regression slopes, suggest that increase of plasma Factor VII coagulant activity as a function of plasma triglyceride levels is attributable to an increase in both mass and activity of Factor VII and that the increase in activity is dependent on an increase of Factor VII-phospholipid complex rather than activated Factor VII double-chain form. The ratio between the slopes of the regression straight line of Factor VII mass and Factor VII-phospholipid complex in relation to triglycerides was 2.23 (95% confidence limits 1.74–2.50), thus indicating that the contribution of Factor VII mass is prevalent over that of the Factor VII-phospholipid complex.
Shinji Nakao - One of the best experts on this subject based on the ideXlab platform.
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Atorvastatin reduces plasma levels of Factor VII activity and Factor VII antigen in patients with hyperlipidemia.
Journal of atherosclerosis and thrombosis, 2002Co-Authors: Eriko Morishita, Shinji Minami, Chizuko Ishino, Masanori Kanno, Chika Uotani, Hidesaku Asakura, Tamotsu Matsuda, Shinji NakaoAbstract:Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor currently in clinical use. Its effects on plasma levels of Factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of atorvastatin treatment, Factor VII activity (FVIIc) and Factor VII antigen (FVIIag) levels had decreased by 13% (p < 0.0001) and 12% (p < 0.0001), respectively. The decreased concentrations of serum triglycerides correlated with decreases in FVIIc levels (r = 0.54, p = 0.0023) and FVIIag levels (r = 0.59, p = 0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were seen in activated Factor VII (FVIIa) levels. Plasma concentrations of fibrinogen were slightly, but not significantly, increased at 12 weeks. No significant changes were seen in plasminogen activator inhibitor-1 levels. The effects of atorvastatin on FVII may contribute to a decreased thrombotic potential, resulting in fewer thromboembolic events, including a reduction in coronary heart disease.
