John H. Griffin - Del Mar CA 92014 Hiroshi Deguchi - Del Mar CA 92130 Jose Fernandez - La Jolla CA 92037
International Classification:
C12Q 156
US Classification:
435 13, 536 179, 600481
Abstract:
The present invention has determined that exogenously added glycosylceramide (GlcCer) and other neutral glycolipids such as the homologous Glc-containing globotriaosylceramide (Gb3Cer), dose-dependently prolonged clotting times of normal plasma in the presence but not absence of APC:protein S, indicating GlcCer or Gb3Cer can enhance protein C pathway anticoagulant activity. In studies using purified proteins, inactivation of factor Va by APC:protein S was enhanced by GlcCer alone and by GlcCer, globotriaosylceramide, lactosylceramide, and galactosylceramide in multicomponent vesicles containing phosphatidylserine and phosphatidylcholine. Thus, the present invention provides neutral glycolipids such as GlcCer and Gb3Cer, as anticoagulant cofactors that contribute to the antithrombotic activity of the protein C pathway. The present invention has also determined that a deficiency of plasma GlcCer is a risk factor for thrombosis. Methods are provided to determine individuals at risk for thrombosis, methods of treatment as well as methods of screening for antithrombotic factors from neutral glycolipids.
Plasma Glucosylceramide Deficiency As Risk Factor For Thrombosis And Modulator Of Anticoagulant Protein C
John Griffin - Del Mar CA, US Hiroshi Deguchi - Del Mar CA, US Jose Fernandez - La Jollal CA, US
International Classification:
A61K031/739
US Classification:
514/054000
Abstract:
The present invention has determined that exogenously added glycosylceramide (GlcCer) and other neutral glycolipids such as the homologous Glc-containing globotriaosylceramide (Gb3Cer), dose-dependently prolonged clotting times of normal plasma in the presence but not absence of APC:protein S, indicating GlcCer or Gb3Cer can enhance protein C pathway anticoagulant activity. In studies using purified proteins, inactivation of factor Va by APC:protein S was enhanced by GlcCer alone and by GlcCer, globotriaosylceramide, lactosylceramide, and galactosylceramide in multicomponent vesicles containing phosphatidylserine and phosphatidylcholine. Thus, the present invention provides neutral glycolipids such as GlcCer and Gb3Cer, as anticoagulant cofactors that contribute to the antithrombotic activity of the protein C pathway. The present invention has also determined that a deficiency of plasma GlcCer is a risk factor for thrombosis. Methods are provided to determine individuals at risk for thrombosis, methods of treatment as well as methods of screening for antithrombotic factors from neutral glycolipids.
Dyslipoproteinemia Associated With Venous Thrombosis
John Griffin - Del Mar CA, US Hiroshi Deguchi - San Diego CA, US Darlene Elias - San Diego CA, US Natalie Pecheniuk - San Diego CA, US
International Classification:
C12Q 1/68 G01N 33/92
US Classification:
435006000, 436071000
Abstract:
The present invention provides methods of determining a human subject's risk for venous thrombosis based on the finding that venous thrombosis patients have significantly lower levels of large HDL particles, HDL-cholesterol and apolipoprotein Al and higher levels of small LDL particles, LDL-cholesterol and apolipoprotein B. Genotyping showed that venous thrombosis patients differed significantly from controls in CETP genotype and that the CETP genotypes found in subjects with VTE are linked to elevated CETP mass and activity. Methods for determining the level of lipids or lipoproteins in plasma or serum samples to determine risk for venous thrombosis are provided. Methods for reducing the risk of venous thrombosis are also provided.
Dyslipoproteinemia Associated With Venous Thrombosis
John H. Griffin - Del Mar CA, US Hiroshi Deguchi - San Diego CA, US Darlene J. Elias - San Diego CA, US Natalie Pecheniuk - San Diego CA, US
International Classification:
G01N 33/92 C12Q 1/68 G01N 33/68
US Classification:
435 6, 436 71, 436 94, 435 29
Abstract:
The present invention provides methods of determining a human subject's risk for venous thrombosis based on the finding that venous thrombosis patients have significantly lower levels of large HDL particles, HDL-cholesterol and apolipoprotein AI and higher levels of small LDL particles, LDL-cholesterol and apolipoprotein B. Genotyping showed that venous thrombosis patients differed significantly from controls in CETP genotype and that the CETP genotypes found in subjects with VTE are linked to elevated CETP mass and activity. Methods for determining the level of lipids or lipoproteins in plasma or serum samples to determine risk for venous thrombosis are provided. Methods for reducing the risk of venous thrombosis are also provided.
Meeting the Challenge of Social Problems Via Agent-Based Simulation: Post-Proceedings of the Second International Workshop on Agent-Based Approaches in Economic and Social Complex Systems
Agent-Based Simulation:From Modeling Methodoloiges to Real-World Applications: Post-Proceedings of the Third International Workshop on Agent-Based Approaches in Economic And Social Complex System 2004