Ray K Chihara

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GLYCOGEN SYNTHASE KINASE3 (GSK3) is a highly conserved serine/threonine kinase involved in a variety of developmental signaling processes. The Arabidopsis (Arabidopsis thaliana) genome encodes 10 GSK3-like kinases that are clustered into four groups. Forward genetic screens have so far uncovered eight mutants, all of which carry gain-of-function mutations(More)
BACKGROUND Pig liver xenotransplantation could offset the shortage of livers available for orthotopic liver transplantation. Studies in pig and baboon liver xenografts revealed the main obstacle to be a lethal thrombocytopenia that occurred within minutes to hours of transplantation. METHODS   We have created a model of xenotransplantation-induced(More)
BACKGROUND Human preformed antibodies continue to recognize porcine xenografts, despite the advent of α-galactosyltransferase knockout (GTKO) pigs. This study examined the potential reactivity of human preformed IgG and IgM antibodies toward antigens in the GTKO pig liver. METHODS Human serum was analyzed for the concentration of IgG, IgM, anti-αgal(More)
BACKGROUND Clinical xenotransplantation is not possible because humans possess antibodies that recognize antigens on the surface of pig cells. Galα-1,3-Gal (Gal) and N-glycolylneuraminic acid (Neu5Gc) are two known xenoantigens. METHODS We report the homozygous disruption of the α1, 3-galactosyltransferase (GGTA1) and the cytidine(More)
BACKGROUND Porcine liver xenografts represent a potential solution to the organ shortage, but thrombocytopenia occurs within minutes to hours after xenotransplantation, preventing clinical application. Recently, it was discovered that porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets. We examined the role of ASGR1 in(More)
BACKGROUND Acute thrombocytopenia was revealed as a limiting factor to porcine liver xenotransplantation from in vitro and in vivo studies using porcine liver in human and baboon transplant models. The asialoglycoprotein receptor 1 (ASGR1) on liver sinusoidal endothelial cells (LSEC) and macrophage antigen complex-1 (Mac-1) on Kupffer cells (KC) mediate(More)
BACKGROUND Hepatic failure has been treated successfully with clinical extracorporeal perfusions of porcine livers. However, dog-to-pig and pig-to-baboon liver xenotransplant models have resulted in severe bleeding secondary to liver xenograft-induced thrombocytopenia. Kupffer cells (KC) are abundant phagocytic cells in the liver. KC express the CD11b/CD18(More)
Liver, pancreas, and kidney allografts preserved in histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions have similar clinical outcomes. This study compares HTK and UW in a large number of standard criteria donor (SCD) and extended criteria donor (ECD) livers at a single center over 5 years. All adult, cadaveric liver and(More)
BACKGROUND Xenotransplantation has the potential to solve the critical shortage of human organs available for allotransplantation. The major barrier to porcine liver xenotransplantation is sequestration of human platelets causing thrombocytopenia. Porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets at least in part through(More)
BACKGROUND Antibody-mediated rejection continues to be an obstacle for xenotransplantation despite development of α1,3-galactosyltransferase knockout (GTKO) pigs. Fibronectin (Fn) from GTKO pigs was identified as a xenoantigen in baboons. N-glycolylneuraminic acid (Neu5Gc), similar to galactose α1,3-galactose, is an antigenic carbohydrate found in pigs. We(More)
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