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BACKGROUND AND AIMS Hepatic bile acid homeostasis is regulated by negative feedback inhibition of genes involved in the uptake and synthesis of bile acids. Bile acids down-regulate the rate-limiting gene for bile acid synthesis, cholesterol 7alpha-hydroxylase (cyp7a), via bile acid receptor (fxr) activation of an inhibitory nuclear receptor, shp. We(More)
As the obligate heterodimer partner to class II nuclear receptors, the retinoid X receptor alpha (RXRalpha) plays a vital physiological role in the regulation of multiple hepatic functions, including bile formation, intermediary metabolism, and endobiotic/xenobiotic detoxification. Many RXRalpha-regulated genes are themselves suppressed in inflamed liver(More)
Cytosolic and nuclear Ca(2+) have been shown to differentially regulate transcription. However, the impact of spatially distinct Ca(2+) signals on mitogen-activated protein kinase-mediated gene expression remains unknown. Here we investigated the role of nuclear and cytosolic Ca(2+) signals in epidermal growth factor (EGF)-induced transactivation of the(More)
Partial hepatectomy leads to an orchestrated regenerative response, activating a cascade of cell signaling events necessary for cell cycle progression and proliferation of hepatocytes. However, the identity of the humoral factors that trigger the activation of these pathways in the concerted regenerative response in hepatocytes remains elusive. In recent(More)
BACKGROUND: Lipopolysaccharide (LPS) treatment of animals down-regulates the expression of hepatic genes involved in a broad variety of physiological processes, collectively known as the negative hepatic acute phase response (APR). Retinoid X receptor alpha (RXRalpha), the most highly expressed RXR isoform in liver, plays a central role in regulating bile(More)
Sodium-dependent uptake of bile acids across the hepatic basolateral membrane is rapidly and profoundly diminished during sepsis, thus contributing to the pathogenesis of sepsis-associated cholestasis. This effect is mediated by endotoxin or effector cytokines, which reduce expression of several hepatobiliary transporters, including the sodium-dependent(More)
BACKGROUND Orthotopic liver transplantation (OLT) is an effective treatment for fulminant hepatic failure (FHF), but postOLT mortality is higher for patients with FHF than for patients with other indications for OLT. In the current study, a large cohort of patients who underwent OLT for FHF was evaluated to develop and validate a system useful for(More)
OBJECTIVE To determine if immunomodulatory treatment including intravenous immunoglobulin (IVIG) can favorably affect survival in neontatal hemochromatosis (NH) diagnosed postnatally because it can effectively prevent occurrence of NH when applied during gestations at risk. STUDY DESIGN We treated 16 newborn infants with liver failure due to NH with(More)
OBJECTIVES To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors. STUDY DESIGN A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with(More)
In recent years the discovery of a number of major transporter proteins expressed in the liver and intestine specifically involved in bile acid transport has led to improved understanding of bile acid homeostasis and the enterohepatic circulation. Sodium (Na(+))-dependent bile acid uptake from portal blood into the liver is mediated primarily by the Na(+)(More)