Learn More
BACKGROUND People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal. METHODS We sequenced the coding and promoter regions of the gene for bilirubin(More)
The human Dubin-Johnson syndrome and its animal model, the TR(-) rat, are characterized by a chronic conjugated hyperbilirubinemia. TR(-) rats are defective in the canalicular multispecific organic anion transporter (cMOAT), which mediates hepatobiliary excretion of numerous organic anions. The complementary DNA for rat cmoat, a homolog of the human(More)
PURPOSE To evaluate their susceptibility to audiogenic seizures, five groups of knockout mice with various forms of fragile X genetic involvement [hemizygous males (n = 46), and homozygous (n = 38) and heterozygous females (n = 45), and their normal male (n = 45) and female (n = 52) littermates] were studied. METHODS All mouse groups were tested at ages(More)
Crigler-Najjar syndrome type I (CN-I) is caused by an inherited absence of UDP-glucuronosyltransferase activity toward bilirubin (B-UGT), resulting in severe non-hemolytic unconjugated hyperbilirubinemia. Based on the expression of cDNAs in COS cells, two UGT isoforms in human liver, B-UGT1 and B-UGT2, have been reported to catalyze bilirubin(More)
The absence of fragile-X mental-retardation protein (FMRP) results in fragile-X syndrome. Two other fragile-X-related (FXR) proteins have been described, FXR1P and FXR2P, which are both very similar in amino acid sequence to FMRP. Interaction between the three proteins as well as with themselves has been demonstrated. The FXR proteins are believed to play a(More)
To investigate the mechanism of sepsis-associated hyperbilirubinemia we have studied hepatocanalicular transport of organic anions in a rat model of endotoxemia. Rats were injected intravenously with lipopolysaccharides (LPS), and at different times after injection, canalicular transport of 2,4-dinitrophenyl-S-glutathione (GS-DNP), as a model organic anion,(More)
The secretion of a glutathione-S-conjugate, dinitrophenyl-glutathione (GS-DNP) was studied in the Caco-2 cells, a cultured human colonic adenocarcinoma cell line with many of the characteristics of enterocytes. The labelled glutathione conjugate was generated within the cell by incubation with 14C-labelled 1-chloro-2,4-dinitrobenzene (CDNB). This compound(More)
Oxidative reactions, such as lipid oxidation and the formation of oxygen radicals, are involved in the pathophys-iology of arteriosclerosis and coronary heart disease (CHD) (1). Bilirubin, the metabolic waste product of heme degradation, is an endogenous antioxidant and could thus have a protective effect against CHD (2). In vitro, conjugated and(More)
The fragile X [fra(X)] syndrome is manifested phenotypically as a developmental disability comprised mainly of moderate-to-severe mental retardation (MR). Deficits are especially evident in auditory and visual short-term memory. Recently, an FMR1 knockout mouse developed by the Dutch-Belgian Fragile X Consortium demonstrated significantly lower(More)
We have studied regulation of the multidrug resistance protein 2 (mrp2) during bile duct ligation (BDL) in the rat. In hepatocytes isolated after 16, 48, and 72 hours of BDL, mrp2-mediated dinitrophenyl-glutathione (DNP-GS) transport was decreased to 65%, 33%, and 33% of control values, respectively. The impaired mrp2-mediated transport coincided with(More)