Genomes and Genes
Summary: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).
Publications363 found, 100 shown here
- Cholestasis and cholestatic syndromesGideon M Hirschfield
Liver Centre, Toronto Western Hospital, Department of Medicine, University of Toronto, Toronto, Canada
Curr Opin Gastroenterol 25:175-9. 2009..Cholestatic liver injury is encountered across a wide variety of clinical scenarios ranging from toxin-induced, genetic, to autoimmune in nature. This review summarizes recent findings from what is a burgeoning clinical field...
- Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liverAnne T Nies
Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
Hepatology 50:1227-40. 2009..0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P = 0.03)...
- Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasisBeth A Carter
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, TX 77030, USA
Nat Clin Pract Gastroenterol Hepatol 4:277-87. 2007..its association with hepatic complications described, the precise etiology of parenteral nutrition associated cholestasis (PNAC) remains a mystery; however, our understanding of the molecular components that contribute to PNAC has ..
- Bile-acid-induced cell injury and protectionMaria J Perez
Department of Biochemistry and Molecular Biology Campus Miguel de Unamuno E D 129, Salamanca, Spain
World J Gastroenterol 15:1677-89. 2009..Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties...
- Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotypeShadi Abu-Hayyeh
Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
Hepatology 57:716-26. 2013Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death...
- The role of inflammation in cholestasis: clinical and basic aspectsAstrid Kosters
Texas Children s Liver Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
Semin Liver Dis 30:186-94. 2010..Disruption and dysregulation of this excretory pathway result in cholestasis, leading to the intrahepatic accumulation of bile acids and other toxic compounds with progression of liver ..
- Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediatorsHernan E Gonzalez
Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
Am J Physiol Gastrointest Liver Physiol 282:G991-G1001. 2002Hepatocyte gap junction proteins, connexins (Cxs) 26 and 32, are downregulated during obstructive cholestasis (OC) and lipopolysaccharide hepatocellular cholestasis (LPS-HC)...
- CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in miceMartin Wagner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
Hepatology 42:420-30. 2005..enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) ..
- Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsisAndreas Geier
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Aachen University, Germany
Nat Clin Pract Gastroenterol Hepatol 3:574-85. 2006b>Cholestasis is a common complication in patients with extrahepatic bacterial infection and sepsis. This article gives a comprehensive overview of the molecular and cellular mechanisms of sepsis-associated cholestasis...
- Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasisHiroshi Uchinami
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Hepatology 44:420-9. 2006b>Cholestasis occurs in a variety of clinical settings and often results in liver injury and secondary biliary fibrosis. Several matrix metalloproteinases (MMPs) are upregulated in the liver during cholestasis...
- Bile salt transporters: molecular characterization, function, and regulationMichael Trauner
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl Franzens University, School of Medicine, Graz, Austria
Physiol Rev 83:633-71. 2003..During bile secretory failure (cholestasis), bile salt transport proteins undergo adaptive responses that serve to protect the liver from bile salt ..
- Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activityFrank Chen
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA
Gastroenterology 126:756-64. 2004The mechanisms by which mutations in the familial intrahepatic cholestasis-1 gene cause Byler's disease (progressive familial intrahepatic cholestasis type 1) are unknown.
- Parenteral nutrition-associated liver complications in childrenImad F Btaiche
Department of Pharmacy Services, University of Michigan Health System, Ann Arbor 48109 0008, USA
Pharmacotherapy 22:188-211. 2002..nutrition is associated with complications affecting the hepatobiliary system, such as cholelithiasis, cholestasis, and steatosis...
- Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone diseaseThierry Claudel
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria
Biochim Biophys Acta 1812:867-78. 2011..Hereditary and acquired alterations of NRs contribute to our understanding of the pathogenesis of cholestasis and gallstone disease. Moreover, NRs may represent attractive drug targets for these disorders...
- "Let there be bile"--understanding hepatic injury in cholestasisRonald J Sokol
Department of Pediatrics, Pediatric Liver Center and Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine and The Children s Hospital, Denver, CO 80218 1088 USA
J Pediatr Gastroenterol Nutr 43:S4-9. 2006..the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids in cholestasis. Steatocholestasis is the combined presence of hepatic steatosis and cholestasis, common in genetic causes of ..
- Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cellsSebastien Antherieu
INSERM UMR991, Liver Metabolisms and Cancer, Rennes, France
Hepatology 57:1518-29. 2013Drugs induce cholestasis by diverse and still poorly understood mechanisms in humans...
- Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liverU Beuers
Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany
Hepatology 33:1206-16. 2001..taurine-conjugated UDCA (TUDCA) was studied in the experimental model of taurolithocholic acid (TLCA)-induced cholestasis on bile flow, hepatobiliary exocytosis, distribution of PKC isoforms, and density of the apical conjugate ..
- Bile acid transporters and regulatory nuclear receptors in the liver and beyondEmina Halilbasic
Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria
J Hepatol 58:155-68. 2013..defects of BA transporters are involved in the pathogenesis of several hepatobiliary disorders including cholestasis, gallstones, fatty liver disease and liver cancer, but also play a role in intestinal and metabolic disorders ..
- Meta-analysis of randomized trials comparing the patency of covered and uncovered self-expandable metal stents for palliation of distal malignant bile duct obstructionAtif Saleem
Department of Internal Medicine, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA
Gastrointest Endosc 74:321-327.e1-3. 2011..Self-expandable metal stents (SEMSs) are used for palliation of malignant biliary obstruction...
- TNFalpha is required for cholestasis-induced liver fibrosis in the mouseErwin Gabele
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Biochem Biophys Res Commun 378:348-53. 2009..Thus, our data indicate that TNFalpha induces hepatotoxicity and promotes fibrogenesis in the BDL model...
- Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodentsJames L Boyer
Liver Center, Yale University School of Medicine, New Haven, CT 06520, USA
Am J Physiol Gastrointest Liver Physiol 290:G1124-30. 2006..These results indicate that expression of Ostalpha and Ostbeta are highly regulated in response to cholestasis and that this response is dependent on the FXR bile acid receptor.
- Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventionsAndreas E Kremer
Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Hepatology 56:1391-400. 2012..In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis...
- Hepatobiliary transporters and drug-induced cholestasisChristiane Pauli-Magnus
Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland
Hepatology 44:778-87. 2006..by pre-existing hepatic disease and genetic factors, which contribute to the development of drug-induced cholestasis in susceptible individuals...
- An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acidsW Xie
Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 98:3375-80. 2001..step in the metabolism and excretion of bile acids and is necessary to avoid pathologic conditions such as cholestasis and liver damage...
- Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasisSalvatore Modica
Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
Gastroenterology 142:355-65.e1-4. 2012b>Cholestasis is a liver disorder characterized by impaired bile flow, reduction of bile acids (BAs) in the intestine, and retention of BAs in the liver. The farnesoid X receptor (FXR) is the transcriptional regulator of BA homeostasis...
- Phosphoinositide 3-kinase/protein kinase B signaling pathway is involved in estradiol 17β-D-glucuronide-induced cholestasis: complementarity with classical protein kinase CAndrea C Boaglio
Institute of Experimental Physiology, National Scientific and Technical Research Council University of Rosario, Rosario, Argentina
Hepatology 52:1465-76. 2010..We assessed whether phosphoinositide 3-kinase (PI3K) is involved in E(2)17G-induced cholestasis. E(2)17G activated PI3K according to an assessment of the phosphorylation of the final PI3K effector, protein ..
- Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video)Anshu Mahajan
Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
Gastrointest Endosc 70:303-9. 2009..Recently, fully covered self-expandable metal stents (CSEMSs) with anchoring fins have become available...
- Endoscopic bilateral metal stent placement for advanced hilar cholangiocarcinoma: a pilot study of a newly designed Y stentJung Hyun Lee
Department of Internal Medicine, Pusan National University College of Medicine, Seo Gu, Busan, Korea
Gastrointest Endosc 66:364-9. 2007....
- Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerationsGernot Zollner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria, and Karolinska University Hospital Huddinge, Stockholm, Sweden
Mol Pharm 3:231-51. 2006b>Cholestasis results in intrahepatic accumulation of cytotoxic bile acids which cause liver injury ultimately leading to biliary fibrosis and cirrhosis...
- Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresiaPranavkumar Shivakumar
Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Ohio 45229 3039, USA
J Clin Invest 114:322-9. 2004..Thus, IFN-gamma-driven obstruction of bile ducts is a key pathogenic mechanism of disease and may constitute a therapeutic target to block disease progression in patients with biliary atresia...
- Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresiaPranavkumar Shivakumar
Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
Gastroenterology 133:268-77. 2007..Here, we investigate this question by examining the role of T lymphocytes in the destruction of extrahepatic bile ducts of neonatal mice using an experimental model of biliary atresia...
- A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstructionH Isayama
Department of Gastroenterology, University of Tokyo, Tokyo, Japan
Gut 53:729-34. 2004..Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking...
- CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injuryNobuyuki Tamaki
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
Am J Physiol Gastrointest Liver Physiol 294:G498-505. 2008..In conclusion, cholestasis induces CHOP-mediated ER stress and triggers hepatocyte cell death, and CHOP deficiency attenuates this cell ..
- LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in miceFuyumi Isayama
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, USA
Am J Physiol Gastrointest Liver Physiol 290:G1318-28. 2006..to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis. Wild-type mice and CD14 knockout mice (CD14(-/-)) underwent sham operation or bile duct ligation and were ..
- Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasisYoung Joo Park
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Hepatology 47:1578-86. 2008..Shp(-/-) mice show increased sensitivity in this model of acute obstructive cholestasis, with greater numbers of bile infarcts and higher mortality than wild-type C57BL/6 mice...
- Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasisYaping Liu
Nuclear Receptor Functional Analysis, High Thruput Biology, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
J Clin Invest 112:1678-87. 2003..agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in ..
- Cholestasis: human disease and experimental animal modelsEmilio Alberto Rodríguez-Garay
Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Universidad Nacional de Rosario, Rosario, Argentina
Ann Hepatol 2:150-8. 2003b>Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common...
- Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasisStefano Fiorucci
Gastroenterologia ed Epatologia, Policlinico Monteluce, Perugia, Italy
J Pharmacol Exp Ther 313:604-12. 2005..acid (6-ECDCA or INT-747), a semisynthetic bile acid derivative and potent FXR ligand, in a model of cholestasis induced by 5-day administration of 17alpha-ethynylestradiol (E(2)17alpha) to rats...
- Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasisChien Yi Chen
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, No 7 Chung Shan South Road, Taipei 100, Taiwan
J Pediatr 145:317-21. 2004To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC).
- Soybean oil fat emulsion to prevent TPN-induced liver damage: possible molecular mechanisms and clinical implicationsMasuhiro Nishimura
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc, Naruto, Tokushima, Japan
Biol Pharm Bull 29:855-62. 2006Long-term total parenteral nutrition (TPN) is known to be associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally...
- Facial features in Alagille syndrome: specific or cholestasis facies?Binita M Kamath
Division of Gastroenterology and Nutrition, The Children s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Am J Med Genet 112:163-70. 2002Alagille syndrome is a complex multisystem disorder characterized by bile duct paucity, cholestasis, cardiac defects, vertebral anomalies, ophthalmologic changes, and facial dysmorphism...
- Polyurethane-covered metal stent for management of distal malignant biliary obstructionHiroyuki Isayama
Department of Gastroenterology, Department of Endoscopy and Endoscopic Surgery, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
Gastrointest Endosc 55:366-70. 2002..The efficacy of polyurethane-covered metal expandable stents for treatment of neoplastic distal biliary obstruction was analyzed...
- Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in miceMin Yang
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
Toxicol Lett 224:186-95. 2014..To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL)...
- Idiopathic cholestasis as a paraneoplastic phenomenon in Hodgkin's lymphomaStefan K Barta
Department of Medicine, St Luke s Roosevelt Hospital Center, New York, NY, USA
Clin Lymphoma Myeloma 7:77-82. 2006Paraneoplastic cholestasis is an uncommon presenting symptom in Hodgkin's lymphoma (HL). Two distinct entities causing this clinical picture have been described: idiopathic cholestasis and vanishing bile duct syndrome (VBDS)...
- Nuclear receptors in liver diseaseMartin Wagner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria
Hepatology 53:1023-34. 2011....
- Nuclear receptor regulation of the adaptive response of bile acid transporters in cholestasisMartin Wagner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Semin Liver Dis 30:160-77. 2010Although hereditary or acquired defects in hepatobiliary transporter systems cause or predispose to cholestasis, adaptive bile acid transporter changes can counteract cholestasis by reducing hepatocellular and systemic concentrations of ..
- Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasisKatryn Allen
Department of Pharmacology, Toxicology, and Experimental Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Am J Pathol 178:175-86. 2011Inflammation contributes to liver injury during cholestasis. The mechanism by which cholestasis initiates an inflammatory response in the liver, however, is not known. Two hypotheses were investigated in the present studies...
- Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applicationsMarcelo G Roma
Institute of Experimental Physiology IFISE CONICET, Faculty of Biochemical and Pharmacautical Sciences, National University of Rosario, Suipacha 570, S2002LRL Rosario, Argentina
Clin Sci (Lond) 121:523-44. 2011..UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane recruitment of death ..
- Oxidative stress and the pathogenesis of cholestasisBryan L Copple
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Semin Liver Dis 30:195-204. 2010b>Cholestasis is a reduction in bile flow that occurs from a variety of causes in humans. This produces hepatocellular injury and fibrosis...
- Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in ratsLi Li Ding
Department of Pharmacognosy, China Pharmaceutical University, Nanjing 201009, China
J Ethnopharmacol 140:222-9. 2012..Danning tablet, as a composite prescription of traditional Chinese medicine, has been used clinically to relieve liver and gallbladder diseases in China. However, the mechanisms involved are still unclear...
- Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liverC J Soroka
Liver Center and Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8019, USA
Hepatology 33:783-91. 2001..export pump multidrug resistance-associated protein 2 (Mrp2) is diminished in experimentally induced models of cholestasis. In this study we have examined the localization and expression of Mrp3, another member of the multidrug ..
- Orthotopic liver transplantation for cholestatic diseasesW Patkowski
Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland
Hepatogastroenterology 57:605-10. 2010..0% of cases. The aim of this study was to overview retrospective indications for operation and results of patients who underwent LTx for cholestatic diseases...
- A mouse model of cholestasis-associated cholangiocarcinoma and transcription factors involved in progressionHeping Yang
Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, Department of Medicine, Keck School of Medicine USC, Los Angeles, CA 90033, USA
Gastroenterology 141:378-88, 388.e1-4. 2011b>Cholestasis contributes to hepatocellular injury and promotes liver carcinogenesis. We created a mouse model of chronic cholestasis to study its effects on progression of cholangiocarcinoma and the oncogenes involved.
- FXR and PXR: potential therapeutic targets in cholestasisJohan W Jonker
Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
J Steroid Biochem Mol Biol 130:147-58. 2012..receptor (NR) family of ligand-modulated transcription factors are implicated in the adaptive response to cholestasis. NRs coordinately regulate bile acid and phospholipid transporter genes required for hepatobiliary transport, ..
- Role of breast cancer resistance protein in the adaptive response to cholestasisAlbert Mennone
Department of Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8019, USA
Drug Metab Dispos 38:1673-8. 2010..and food toxins, Bcrp can also transport bile acids and, therefore, may participate in the adaptive response to cholestasis. Bile duct ligation (BDL), an experimental model of obstructive cholestasis, was performed in male wild-type (..
- RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling caspase-8- and JNK-dependent compensatory cell proliferationMihael Vucur
Department of Medicine III, University Hospital RWTH Aachen, D 52074 Aachen, Germany
Cell Rep 4:776-90. 2013..Moreover, RIP3 promotes the development of jaundice and cholestasis, because its activation suppresses compensatory proliferation of cholangiocytes and hepatic stem cells...
- Nuclear receptors as drug targets in cholestasis and drug-induced hepatotoxicityGernot Zollner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
Pharmacol Ther 126:228-43. 2010..or tested for the treatment of diabetes, dyslipidemia, fatty liver disease, cancer, drug hepatotoxicity and cholestasis. The hydrophilic bile acid ursodeoxycholic acid is currently the only available drug to treat cholestasis but ..
- Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivityMing Huei Chou
Institute of Basic Medical Sciences, National Chang Kung University, Tainan, Taiwan
PLoS ONE 7:e34903. 2012b>Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia...
- Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in miceTakahiro Kodama
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Gastroenterology 138:2487-98, 2498.e1-7. 2010..It is not clear whether thrombocytopenia itself affects liver fibrosis...
- Comparison of axial force and cell width of self-expandable metallic stents: which type of stent is better suited for hilar biliary strictures?Tsuyoshi Mukai
Department of Gastroenterology, Gifu Municipal Hospital, 7 1 Kashima cho, Gifu 500 8513, Japan
J Hepatobiliary Pancreat Sci 18:646-52. 2011..However, few reports have compared the performance of the various SEMSs. In addition to long-term patency, maneuverability during initial placement and feasibility of re-intervention for the stent occlusion are also very important...
- Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated miceMartin Wagner
Department of Medicine, Karl Franzens University, Graz, Austria
Gastroenterology 125:825-38. 2003b>Cholestasis induces changes in hepatic adenosine triphosphate-binding cassette (ABC) transporter expression...
- Drug-induced cholestasisLakshumanan S Velayudham
Storr Liver Unit, Westmead Millennium Institute, University of Sydney, NSW, Australia
Expert Opin Drug Saf 2:287-304. 2003Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow...
- Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medicationFernando A Crocenzi
Instituto de Fisiología Experimental IFISE, Facultad de Ciencias Bioquímicas y Farmacéuticas CONICET U N R, S2002LRL, Rosario, Argentina
Curr Med Chem 13:1055-74. 2006..as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1...
- Altered localization and activity of canalicular Mrp2 in estradiol-17beta-D-glucuronide-induced cholestasisAldo D Mottino
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 0305, USA
Hepatology 35:1409-19. 2002..mixed plasma and intracellular membranes suggested partial internalization of Mrp2 during the acute phase of cholestasis at 20 minutes and during the period of recovery from cholestasis at 75 minutes, which returned to control ..
- Neonatal cholestasisFrederick J Suchy
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA
Pediatr Rev 25:388-96. 2004
- Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarismWikrom Karnsakul
Department of Pediatrics, Section of Gastroenterology and Nutrition, West Virginia University School of Medicine, Morgantown, WV 26506 9214, USA
Ann Hepatol 6:97-103. 2007Congenital hypopituitarism is an uncommon cause of neonatal cholestasis. Little is known about the effect of anterior pituitary hormone on hepatic functions.
- Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasisS Teng
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
Br J Pharmacol 151:367-76. 2007..As PXR alters the expression of numerous hepatic bile acid transporters, we sought to delineate their potential role in hepatoprotection...
- Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosisYu Yamaura
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma machi, Kanazawa, Japan
PLoS ONE 7:e30250. 2012..study, we compared the changes of the plasma miRNA expressions by acute liver injury (hepatocellular injury or cholestasis) and chronic liver injury (steatosis, steatohepatitis and fibrosis) using rat models made by the administration ..
- Sepsis-induced cholestasisNisha Chand
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298 0341, USA
Hepatology 45:230-41. 2007
- Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the ratF A Crocenzi
Instituto de Fisiología Experimental IFISE, Facultad de Ciencias Bioquímicas y Farmacéuticas CONICET UNR, Rosario, Argentina
Gut 52:1170-7. 2003Taurolithocholate induced cholestasis is a well established model of drug induced cholestasis with potential clinical relevance. This compound impairs bile salt secretion by an as yet unclear mechanism.
- Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injuryJi Qi Yan
Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Road, Shanghai 200025, China
World J Gastroenterol 13:6598-602. 2007..To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury...
- Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasisZ H Aghai
Department of Pediatrics, Division of Neonatology, Cooper University Hospital Robert Wood Johnson Medical School, One Cooper Plaza, Camden, NJ 08103, USA
J Perinatol 26:550-5. 2006..The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians...
- Update on the treatment of the pruritus of cholestasisNora V Bergasa
State University of New York at Downstate, USA
Clin Liver Dis 12:219-34, x. 2008The pruritus of cholestasis is a difficult clinical problem to manage. It can be severe and interfere with sleep. Clinical behavioral studies have confirmed that the pruritus is mediated at least in part by endogenous opioids...
- Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in ratsFernando A Crocenzi
Instituto de Fisiologia Experimental, Universidad Nacional de Rosario, Argentina
Am J Physiol Gastrointest Liver Physiol 285:G449-59. 2003..protein 2 (Mrp2) was previously suggested to be involved in estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ..
- Nuclear receptors, bile-acid detoxification, and cholestasisJiezhong Chen
School of Pharmacy and Applied Science, Faculty of Science, Technology and Engineering, La Trobe University, Bendigo, VIC 3550, Australia
Lancet 367:454-6. 2006
- High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasisTheresa C Willis
United States Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
JPEN J Parenter Enteral Nutr 34:32-7. 2010Extremely few data are available about the natural history of parenteral nutrition (PN)-associated cholestasis. The authors evaluated a cohort of infants at a large center to determine the outcome of PN-associated cholestasis in infants ..
- Disruption of the growth hormone--signal transducer and activator of transcription 5--insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasisLeander Blaas
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
Hepatology 51:1319-26. 2010..both in hepatocytes and cholangiocytes in the multidrug resistance gene 2 knockout (Mdr2(-/-)) mouse model of cholestasis. Double knockout mice develop an early and severe liver fibrosis phenotype, accompanied by perturbed expression ..
- Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothersG Mazzella
Dipartimento di Malattie dell Apparato Digerente, del Metabolismo and delle Malattie Infettive, Azienda Ospedaliera di Bologna, Universita di Bologna, Italy
Hepatology 33:504-8. 2001Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1...
- Localization status of hepatocellular transporters in cholestasisFernando A Crocenzi
Instituto de Fisiología Experimental IFISE, CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, S2002LRL, Rosario, Argentina
Front Biosci (Landmark Ed) 17:1201-18. 2012..Exacerbated internalization of hepatocellular transporters occurs in several experimental models of cholestasis, and also in most human cholestatic liver diseases...
- Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case seriesD L Cahen
Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
Endoscopy 40:697-700. 2008..Nevertheless, before FCSEMS can become an acceptable treatment option for benign CBD strictures, innovative stent design modifications are necessary and removability must be ascertained...
- Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathwayYan Ding
Department of Gastroenterology and Hepatology, Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, PR China
Eur J Pharmacol 590:377-86. 2008..The effects are mainly due to antagonizing pro-inflammatory cytokines and mediators, inhibiting oxidative damage, improving hepatic microcirculation, reducing impairment signals, and controlling neutrophil infiltration...
- Partially covered self-expandable metallic stents for benign biliary strictures due to chronic pancreatitisB Behm
Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
Endoscopy 41:547-51. 2009..We evaluated the temporary placement of partially covered self-expandable metallic stents (PCMS) in patients with BBS due to chronic pancreatitis...
- Sonographic diagnosis of biliary atresia in pediatric patients using the "triangular cord" sign versus gallbladder length and contractionKimio Kanegawa
Department of Radiology, Kobe Children s Hospital, 1 1 1 Takakuradai Suma ku, Kobe 654 0081, Japan
AJR Am J Roentgenol 181:1387-90. 2003..A retrospective review was performed to evaluate the importance of the "triangular cord" sign in comparison with gallbladder length and contraction for the diagnosis of biliary atresia in pediatric patients...
- Itch: scratching more than the surfaceR Twycross
Sir Michael Sobell House, Churchill Hospital, Oxford, OX3 7LJ, UK
QJM 96:7-26. 2003..g. dermatitis), neuropathic (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or psychogenic...
- New molecular insights into the mechanisms of cholestasisMartin Wagner
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Laboratory of Experimental and Molecular Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
J Hepatol 51:565-80. 2009..has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause ..
- Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrateLieke M van der Velden
Department of Metabolic and Endocrine Diseases, University Medical Center UMC Utrecht, The Netherlands
Hepatology 51:286-96. 2010..is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It presents either as a progressive (progressive familial intrahepatic cholestasis type 1 [PFIC1]) or ..
- Cellular regulation of hepatic bile acid transport in health and cholestasisM Sawkat Anwer
Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, 200 Westboro Road, N Grafton, MA 01536, USA
Hepatology 39:581-90. 2004
- Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasisUlrich Beuers
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany
Nat Clin Pract Gastroenterol Hepatol 3:318-28. 2006..synthesis, targeting and apical membrane insertion of key transporters, seems to be relevant in more advanced cholestasis. In intrahepatic cholestasis of pregnancy, stimulation of impaired hepatocellular secretion could be crucial ..
- Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liverM G Donner
Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Hepatology 34:351-9. 2001b>Cholestasis induces down-regulation of multidrug resistance protein 2 (Mrp2, symbol Abcc2), which is localized to the canalicular membrane...
- Inhibition of Na+-taurocholate Co-transporting polypeptide-mediated bile acid transport by cholestatic sulfated progesterone metabolitesShadi Abu-Hayyeh
Institute for Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom
J Biol Chem 285:16504-12. 2010..progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy...
- A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstructionJennifer J Telford
St Paul s Hospital, Vancouver, British Columbia, Canada
Gastrointest Endosc 72:907-14. 2010..The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency...
- Benefit of farnesoid X receptor inhibition in obstructive cholestasisCatherine Stedman
Department of Clinical Pharmacology, Molecular Pharmacology Laboratory, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney NSW 2145, Australia
Proc Natl Acad Sci U S A 103:11323-8. 2006..FXR knockout (KO) mice were found to be protected from obstructive cholestasis. Concurrent deletion of FXR also could ameliorate an increase in liver injury that is seen usually in pregnane ..
- Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisitedGustav Paumgartner
Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany
Hepatology 36:525-31. 2002..Anticholestatic effects of UDCA have also been reported in intrahepatic cholestasis of pregnancy, liver disease of cystic fibrosis, progressive familial intrahepatic cholestasis, and chronic ..
- Mrp4-/- mice have an impaired cytoprotective response in obstructive cholestasisAlbert Mennone
Liver Center and Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
Hepatology 43:1013-21. 2006..In conclusion, hepatic Mrp4 plays a unique and essential protective role in the adaptive response to obstructive cholestatic liver injury...
- Pharmacological actions of curcumin in liver diseases or damageYadira Rivera-Espinoza
Departamento de Graduados e Investigacion en Alimentos, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Carpio y Plan de Ayala, Mexico City, Mexico
Liver Int 29:1457-66. 2009..Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl(4)) intoxication; moreover, it reverses CCl(4) ..
- Temporary placement of covered self-expandable metal stents in benign biliary strictures: a new paradigm? (with video)Michel Kahaleh
Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
Gastrointest Endosc 67:446-54. 2008..Benign biliary strictures (BBS) are usually managed with plastic stents, whereas placement of uncovered metallic stents has been associated with failure related to mucosal hyperplasia...
- MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromesMichael Trauner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria
Semin Liver Dis 27:77-98. 2007..bile secretion, hereditary and acquired ABC transporter defects play a central role in the pathogenesis of cholestasis. Defects of the phospholipid export pump MDR3 ( ABCC4) result in impaired biliary excretion of ..
- Nuclear receptors as therapeutic targets in cholestatic liver diseasesGernot Zollner
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Br J Pharmacol 156:7-27. 2009b>Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis...
- Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseasesG Zollner
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens University Graz, Austria
Hepatology 33:633-46. 2001..could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice...
- Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasisFrancisco J Padillo
Unit of Hepatobiliary Surgery, Department of General Surgery, Reina Sofia University Hospital, Avda Menendez Pidal s n 14 004, Cordoba, Spain
Free Radic Res 38:697-704. 2004..MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status ..
- Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acidsHanns Ulrich Marschall
Karolinska Institutet, Department of Medicine at Karolinska University Hospital Huddinge, S 14186 Stockholm, Sweden
J Lipid Res 47:582-92. 2006..In conclusion, Fxr(-/-) mice detoxify accumulating bile acids in the liver by enhanced hydroxylation reactions probably catalyzed by Cyp3a11. The metabolites formed were excreted into urine, most likely with the participation of Mrp4...
- Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic DiseasStephen C Strom; Fiscal Year: 2010..For example mutations in the bile salt export pump (BSEP) results in severe cholestasis and fibrosis in human patients requiring whole organ transplants, yet the knockout mouse is nearly without a ..
- Histamine modulation of biliary proliferation and damageHeather L Francis; Fiscal Year: 2013..HRs);and (ii) H1HR and H2HR stimulate cholangiocyte growth, whereas H3HR or H4HR inhibit biliary growth during cholestasis. In addition to cholangiocytes, histamine is synthesized mainly from mast cells in response to many pathologies ..
- Liver disease in CF: CFTR controls innate immunity in biliary epitheliumMario Strazzabosco; Fiscal Year: 2013..spontaneous development of CFLD is extremely rare, suggesting that genetic and/or acquired factors other than cholestasis are at play...
- Mechanisms of Neutrophil-induced Liver ToxicityHARTMUT W JAESCHKE; Fiscal Year: 2012..injury (transplantation, tumor resections), alcoholic hepatitis, steatohepatitis and obstructive cholestasis. However, these leukocytes also fulfill a vital host defense function against invading microorganisms...
- Excessive Copper Levels Disrupt Hepatic Nuclear Receptor FunctionClavia Ruth Wooton-Kee; Fiscal Year: 2011..in the Cu-transporting P-type ATPase, ATP7b, and is associated with a variety of symptoms including steatosis, cholestasis, cirrhosis, and liver failure, as well as neurological dysfunction...
- Biliary Atresia, Cholestatic Liver Diseases, and Cystic Fibrosis: Indiana UniversJean Pappas Molleston; Fiscal Year: 2013..Biliary atresia accounts for more than half of pediatric liver transplants. Genetic causes of neonatal cholestasis include Alagille's syndrome, alpha-1-antitrypsin deficiency, Progressive Familial Intrahepatic Cholestasis ..
- DYSREGULATION OF GSH SYNTHESIS DURING LIVER INJURY AND FIBROSISSHELLY CHI LOO LU; Fiscal Year: 2013..SAMe) prevented the fall in GCL subunits mRNA levels in hepatocytes (UDCA and SAMe) during cholestasis, and in macrophages (SAMe) during LPS treatment...
- Colorado Center for Childhood Liver Disease Research and EducationRonald J Sokol; Fiscal Year: 2013..In cholestasis, impairment of bile flow leads to the accumulation of hepatotoxic bile acids, cholesterol and other compounds ..
- The Pittsburgh Cholestatic Liver Disease ConsortiumBenjamin L Shneider; Fiscal Year: 2013..defects, biliary atresia, cystic fibrosis, mitochondrial hepatopathies and progressive familial intrahepatic cholestasis, lead to significant morbidity and mortality in childhood and frequently necessitate liver transplantation...
- MOLECULAR REGULATION OF ILEAL/RENAL BILE ACID TRANSPORTBenjamin L Shneider; Fiscal Year: 2012..diarrhea, while partial inhibition of ASBT-mediated transport can be used to treat hypercholesterolemia and cholestasis. NIH supported investigations in my laboratory have advanced our understanding of the molecular regulation of ..
- Epigenetic regulation of liver transportersFrederick J Suchy; Fiscal Year: 2013..receptor for bile acids, regulate the expression of liver transport proteins in the normal liver and during cholestasis. We propose that epigenetic modification of chromatin into repressive or permissive configurations provides a ..
- Crosstalk between estrogen and bile acid signaling pathwayRuitang Deng; Fiscal Year: 2013..Among diseases resulted from imbalance of bile acid levels, intrahepatic cholestasis of pregnancy (ICP) and gallstone disease are both associated with sex hormone estrogen...
- The Role of Genetics in Innate Immunity Following CholestasisSamuel M Alaish; Fiscal Year: 2011..A description of the research project follows: Defined as little or no bile flow, cholestasis is a common condition associated with significant and sometimes devastating complications in both children and ..
- Regulation of Hepatic Metabolic Function by Parenteral NutritionDouglas G Burrin; Fiscal Year: 2013..studies in premature piglets show that TPN enriched with phytosterols and n-6 fatty acids (FA) induces hepatic cholestasis, steatosis and inflammation compared to enteral nutrition...
- Structure/Function of Steroid Transforming AKR'sTrevor M Penning; Fiscal Year: 2011..have been associated with 5[unreadable]-reductase deficiency, which results in fatal neonatal hepatitis and cholestasis. Whether these mutations are the molecular basis of this disease has not been established...
- Control of cAMP Mediated Glucagon Response by Bile AcidsNorman H Lee; Fiscal Year: 2011..glucagon responsiveness, which is one of the events associated to the progression of liver disease during cholestasis. The aims of the proposed study are: 1) Identification in vitro by a proteomic approach of the PKC residues ..
- Interplay between metabolism and FXR activation in scoparone signalingBingfang Yan; Fiscal Year: 2013..The central hypothesis of this project is that scoparone metabolites confer potent hepatic protection against cholestasis by efficaciously modulating FXR phosphorylation...
- Functions of MRP2 and MRP3 in Drug DispositionJames M Gallo; Fiscal Year: 2011..gut enterocytes, and is induced at basolateral surfaces of hepatocytes during conditions of liver dysfunction (cholestasis) in which the canalicular route of drug detoxification is blocked...
- Regulation of Sulfotransferases by LXR and its Implication in PathophysiologyWen Xie; Fiscal Year: 2011..of bile acid- and estrogen-metabolizing SULTs will lead to the alleviation of bile acid hepatotoxicity and cholestasis as well as down-regulation of estrogen activity in vivo...
- Drs2p Function in Clathrin-coated Vesicle BuddingTodd R Graham; Fiscal Year: 2013..Moreover, deficiency of a human P4-ATPase (Atp8b1) causes familial intrahepatic cholestasis, a disease where loss of PS asymmetry in the bile canalicular membrane leads to damage of this membrane by ..
- Establichment of CHLA's ChilDREN Clinical CenterKASPER SAONUN WANG; Fiscal Year: 2013..Consortium, along with Alagille syndrome (AGS), alpha-1-antitrypsin deficiency, progressive intrahepatic cholestasis, bile acid synthesis defects, mitochondrial hepatopathies, and cystic fibrosis liver disease, studied under the ..
- Center for the Study of Pediatric CholestasisRonen Arnon; Fiscal Year: 2013..clinical features, the correlation of genotype with phenotype, and prognosis of inherited forms of intrahepatic cholestasis including Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis (..
- Mechanisms of xenobiotic-induced biliary inflammation and fibrosisJames P Luyendyk; Fiscal Year: 2013..The broad, long term goal of this proposal is to elucidate the mechanism whereby xenobiotic-induced cholestasis causes inflammation and fibrosis...
- Rare Liver Disease NetworkRonald J Sokol; Fiscal Year: 2010..The RLDN will focus on investigations of five genetic causes of intrahepatic cholestasis. These disorders have serious if not fatal consequences (without liver transplantation) and severely affect the ..
- Gut bile acids, Fxr, &Fgf15 in total parenteral nutrition-associated cholestasisGrace L Guo; Fiscal Year: 2013..Long-term TPN is associated with a severe complication, TPN-associated cholestasis (TPN-AC). The mechanism underlying the cause of TPN-AC is poorly understood...
- Childhood Liver Disease Research and Education Network (CHiLDREN) - UCSF (CC)Philip Rosenthal; Fiscal Year: 2013..5) Phase l/ll study of new agents to treat cholestasis in children. 6) Study of modifier genes in Alagille Syndrome and Alpha-1-antrypsin disease...
- ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASEMARTIN CONRAD CAREY; Fiscal Year: 2013..biologic techniques to advance fundamental understanding of bile and its two major dysfunctions, namely cholestasis and gallstones of both pigment and cholesterol types, i) The first aim will determine whether enterohepatic ..
- Dysregulated Hypothalamic-pituitary-adrenal Axis During Biliary HyperplasiaSharon Demorrow; Fiscal Year: 2013..liver disease and that this may contribute to the cholangiocyte outgrowth seen in the early stages of cholestasis. The overall objective of this proposal is to determine the consequences of cholestatic liver disease on the ..
- Molecular mechanisms of Bile Duct Proliferation in Mice with Glycosylation DefectMATTHEW JOSEPH RYAN; Fiscal Year: 2012..in either the JAG1 or NOTCH2 genes and characterized by a paucity of bile ducts in the liver with resultant cholestasis. Despite the knowledge of the genes responsible for ALGS, there exists a wide phenotypic variability even ..
- Regulation of Bile Duct Growth in Bile Duct Ligated RatsSHANNON STROUD GLASER; Fiscal Year: 2013..expressed in the liver mainly by cholangiocytes) participates in the homeostasis of the biliary mass during cholestasis and liver damage...
- JAUNDICE NEXT: A diagnostic tool for cholestatic liver disease.Frank Zemlan; Fiscal Year: 2012DESCRIPTION (provided by applicant): Cholestasis (or pathologic jaundice) is the most common sign of liver disease in children and often results from mutations in genes that play a critical role in bile formation and transport...
- Ca2+ Waves in Hepatocytes: Mechanisms and EffectsMichael H Nathanson; Fiscal Year: 2013..InsP3Rs will impair regulated delivery of these transporters to the canalicular membrane, and thus lead to cholestasis. This hypothesis will be tested through three specific aims: (1) The role of impaired Ca2+ signaling in the ..
- Isolation, Identification and Characterization of a Toxin Causing Biliary AtresiaRebecca G Wells; Fiscal Year: 2013..by applicant): Biliary atresia (BA) is a fibro inflammatory disorder that is the leading cause of neonatal cholestasis and the most common indication for liver transplant in the pediatric population...
- ABC-transporter binding proteins and traffickingDaniel F Ortiz; Fiscal Year: 2010..Mutations that cause BSEP retention in the endoplasmic reticulum produce Progressive Familial Intrahepatic Cholestasis type II...
- Control of Sterol and Lipoprotein Homeostasis by miRNAAngel Baldán; Fiscal Year: 2013..HDL lipidation and reverse cholesterol transport, and ATP8B1, a phospholipid flippase linked to intrahepatic cholestasis. The broad goal of this proposal is to determine the role of miR-33 on cholesterol, bile and lipoprotein ..
- Mechanosensitive Signaling and Cholangiocyte SecretionAndrew P Feranchak; Fiscal Year: 2013..Liver diseases associated with impaired bile flow (cholestasis) account for significant morbidity and mortality in both children and adults...
- A genetic model of cholestasis induced neonatalJohn D Schuetz; Fiscal Year: 2013DESCRIPTION (provided by applicant): Recent epidemiological data indicate intrahepatic cholestasis of pregnancy (ICP) has an incidence of between 1.5-4% and is related to serum bile acid concentrations...
- Role of Early Growth Response Factor-1 in Cholestatic Liver InjuryBryan L Copple; Fiscal Year: 2011The overall goal of this proposal is to elucidate the mechanism by which cholestasis triggers production of proinflammatory mediators in the liver...
- Regulation of cholangiocytes by InsP3 receptor isoformsMichael H Nathanson; Fiscal Year: 2012..Abnormal cholangiocyte function results in cholestasis, which is a cardinal manifestation of liver disease...
- The Regulation of Human Hydroxysteroid Sulfotransferase by Nuclear Receptor RORWen Xie; Fiscal Year: 2012..SULT2A1-mediated bile acid sulfation and detoxification play an important role in the prevention and relief of cholestasis. Results from this study may help to understand the role of RORs in the interindividual variation of SULT2A1 ..
- Midwest Children's ConsortiumYumirle P Turmelle; Fiscal Year: 2013..practices and laboratory utilization in an attempt to accelerate identification and referral of infants with cholestasis, focussing on the critical events surrounding presentation, with the goal of defining, then reducing, the ..
- Role of Protein Kinase C in Isoforms in Bile formation and CholestasisMOHAMMED SAWKAT ANWER; Fiscal Year: 2013..Our present understanding of the pathogenesis of cholestasis is based on studies to define the physiological regulation of transporters involved in bile formation and their ..
- Autocrine/Paracrine Regulation of Intrahepatic Bile Duct GrowthGIANFRANCO D ALPINI; Fiscal Year: 2013..secretin receptor gene ablates the proliferative and apoptotic responses of small and large cholangiocytes to cholestasis and liver injury;and (iii) To define the in vitro intracellular mechanisms regulating secretin and secretin ..
- Molecular Mechanisms of Intrahepatic CholestasisBenjamin L Shneider; Fiscal Year: 2013..the applicant): FIC1 disease includes a spectrum of liver problems ranging from "benign" recurrent intrahepatic cholestasis (BRIC) to severe, unremitting and histologically progressive cholestasis (Byler Disease)...
- Organelle Dysfunction and Apoptosis in Liver EpitheliaGregory J Gores; Fiscal Year: 2013..killing via this pathway in vivo, whereas hepatocytes in vivo only become sensitive to TRAIL toxicity during cholestasis. Based upon this preliminary data, we propose the novel CENTRAL HYPOTHESIS that TRAIL induces liver cell death ..
- FXR, nuclear receptors, and transcriptional regulation of liver homeostasisGrace L Guo; Fiscal Year: 2011..Clearly, FXR is important for liver function because FXR deficiency in mice causes cholestasis, dyslipidemia, gallstone, hepatocellular carcinoma and diabetes...
- Investigation of the mechanism by which NPC1 dysfunction leads to liver diseaseLaura Liscum; Fiscal Year: 2012..NPC patients suffer from cholestasis, prolonged jaundice, and hepatosplenomegaly...
- Cholestasis and the Unfolded Protein ResponseRichard M Green; Fiscal Year: 2013..The central hypothesis of this proposal is that XBP1s is protective to the live during cholestasis~ and attenuated hepatic expression of XBP1s results in diminished expression of liver bile salt transporters ..
- The Genetic Basis of Pediatric CholestasisRICHARD JOHN THOMPSON; Fiscal Year: 2012..group of patients was identified some years ago, and their disorder termed progressive familial intrahepatic cholestasis (PFIC)...
- Emory Clinical Center: Childhood Liver Disease Research and Education NetworkRene Romero; Fiscal Year: 2011..Genetic cholestatic liver diseases, such as alagille syndrome, progressive familial intrahepatic cholestasis, mitochondrial hepatopathies and cystic fibrosis associated liver disease are poorly understood and difficult ..
- Tissue specific mechanism of FXR in suppressing bile-acid synthesisGrace L Guo; Fiscal Year: 2011..FXR dysfunction contributes to the development of cholestasis, gallstones, fatty-liver disease, and liver tumor...
- Kinetic and structural analysis of human steroid 5beta-reductase (AKR1D1)Mo Chen; Fiscal Year: 2012..Deficiency in AKR1D1 induces neonatal hepatitis and cholestasis that can be fatal. The exact role of AKR1D1 in sexual and reproductive functions is still under investigation...
- MECHANISMS OF LIVER CELL INJURYGregory Gores; Fiscal Year: 2009..injury in human disease, our program is working on the cellular mechanisms causing hepatocyte injury during cholestasis. Specifically, our long-term goal is to understand the cellular mechanisms by which bile salts, which ..
- THE GENETIC BASIS OF CHOLESTASISLaura N Bull; Fiscal Year: 2010Abstract Liver disease is a cause of substantial morbidity and mortality in the U.S., and cholestasis (impairment of bile flow) is a common and devastating manifestation of liver disease...
- Molecular requirements for proliferation of fetal and adult liver progenitorsStacey S Huppert; Fiscal Year: 2012..A distinguishing characteristic of this syndrome is cholestasis brought on by paucity of bile ducts...
- MECHANISMS OF BILE SECRETION AND CHOLESTASISJAMES LORENZEN BOYER; Fiscal Year: 2013..major function of the liver which is frequently impaired in diseases of the liver resulting in the syndrome of cholestasis. The long term objectives of this grant, funded continuously by NIDDK since 1973, have been to characterize the ..
- Clinical Center: Childhood Liver Disease Research and Education Network (ChiLDRENPETER FRANK WHITINGTON; Fiscal Year: 2013..A major objective of this application is to participate in ChiLDREN as an expert in genetically determined cholestasis (in particular progressive familial intrahepatic cholestasis) and in clinical aspects of infantile cholestatic ..
- Genetic Modifiers of Liver Disease Severity in Alagille SyndromeNancy Bettina Spinner; Fiscal Year: 2013..The liver disease in AGS is characterized pathologically by intrahepatic bile duct paucity, with resulting cholestasis, and ranges from very mild (sub-clinical with only biochemical abnormalities of liver enzymes) to severe, in ..
- PROTEIN COMPARTMENTATIONWILLIAM TOBEY WICKNER; Fiscal Year: 2013..complex, discovered and studied in this work, underlies studies of human arthrogryposis, renal dysfunction, and cholestasis syndromes, caused by mutations in the human VPS33 gene...
- The Childhood Liver Disease Research and Education Network (ChilDREN)SAUL JOSEPH KARPEN; Fiscal Year: 2013..Since there are currently no effective medical therapies for cholestasis, proper exploration of the safety and efficacy of this investigational agent would perfectly fit within the ..
- GROWTH REGULATION OF THE INTRAHEPATIC BILIARY TREEGIANFRANCO D ALPINI; Fiscal Year: 2010..mechanisms regulating the differential proliferative responses of small and large Cholangiocytes to cholestasis and liver injury/toxins will play an important role in the development of therapeutic strategies for the ..
- PHYSICAL CHEMISTRY OF BILIRUBIN & ITS CONJUGATESWILLIAM SPIVAK; Fiscal Year: 1990..bile pigment found in animal models of gallstone formation and premature neonates who are particularly prone to cholestasis, undergoes non-enzymatic alkaline aqueous hydrolysis to insoluble UCB in model bile systems (and in guinea pig ..
- Advancing our Understanding of Rare Pediatric Liver DiseasesKATHLEEN MARY LOOMES; Fiscal Year: 2013..Alagille syndrome (AGS), alpha-one antitrypsin deficiency, progressive familial intrahepatic cholestasis, bile acid synthetic disorders, cystic fibrosis liver disease and neonatal hepatitis...
- MOLECULAR PHYSIOLOGY OF BILIARY LIPID SECRETIONDavid Cohen; Fiscal Year: 2000..cholesterol elimination from the body, and abnormalities in bile secretion may result in gallstone formation, cholestasis, biliary cirrhosis, hypercholesterolemia and fat malabsorption...
- Role of the Renin-Angiotensin System in the Regulation of Biliary ProliferationSHANNON STROUD GLASER; Fiscal Year: 2010..The elucidation of the factors regulating the proliferative responses of cholangiocytes to cholestasis is critical for the development of therapeutic strategies for the treatment of cholestatic liver diseases...
- EFFECT OF VITAMIN E ON HEPATOCYTE STRUCTURE AND FUNCTIONRonald Sokol; Fiscal Year: 1991..clearance of circulating bile acids may be impaired by the vitamin E deficiency state in children with chronic cholestasis and in normal rats, presumably due to alterations in hepatocyte membrane properties essential for transport and ..
- HEPATIC DRUG ELIMINATION IN PREGNANCYMary Vore; Fiscal Year: 2010..TUDC), a bile acid used for the treatment of cholestatic liver disease, including intrahepatic cholestasis of pregnancy (ICP), 2) estradiol-17[3- D-glucuronide (E217G) causes increased permeability of the ..
- HEPATIC DRUG ELIMINATION IN PREGNANCYMary Vore; Fiscal Year: 2007..TUDC), a bile acid used for the treatment of cholestatic liver disease, including intrahepatic cholestasis of pregnancy (ICP), 2) estradiol-17B-D-glucuronide (E217G) causes increased permeability of the hepatocellular ..
- Role of Nrf2 during cholestsis and gallstone formationANGELA SLITT; Fiscal Year: 2009..Gallstones can cause extrahepatic cholestasis by occluding the common bile duct...