keyword
MENU ▼
Read by QxMD icon Read
search

ABCB4

keyword
https://www.readbyqxmd.com/read/28497004/progressive-familial-intrahepatic-cholestasis-type-2-in-an-indian-child
#1
Ira Shah, Sujeet Chilkar
Progressive familial intrahepatic cholestasis (PFIC) is a chronic cholestasis syndrome that begins in infancy and usually progresses to cirrhosis within the first decade of life. There are three varieties of PFIC described: PFIC-1 occurs due to mutations in the ATP8B1 gene mapped to 18q21.31, PFIC-2 due to mutations in ABCB11 mapped to 2q24, and PFIC-3 due to mutations in ABCB4 located on 7q21.12. We report an Indian child whose mutation analysis was suggestive of PFIC-2. He underwent a biliary diversion at 3½ years of age but subsequently died secondary to massive hematemesis...
June 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28436434/phosphatidylethanolamine-dynamics-are-required-for-osteoclast-fusion
#2
Atsushi Irie, Kei Yamamoto, Yoshimi Miki, Makoto Murakami
Osteoclasts, responsible for bone resorption, are multinucleated cells formed by cell-cell fusion of mononuclear pre-osteoclasts. Although osteoclast fusion is a pivotal step for osteoclastogenesis, little is known about the mechanism involved. To clarify the underlying process, we investigated dynamics of membrane phospholipids during osteoclastogenesis in vitro. We found that the cellular content of phospholipids, phosphatidylethanolamine (PE) in particular, was increased during osteoclast differentiation...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28390947/expression-patterns-of-nuclear-receptors-in-parenchymal-and-non-parenchymal-mouse-liver-cells-and-their-modulation-in-cholestasis
#3
Ester Gonzalez-Sanchez, Delphine Firrincieli, Chantal Housset, Nicolas Chignard
Nuclear receptors (NR), the largest family of transcription factors, control many physiological and pathological processes. To gain insight into hepatic NR and their potential as therapeutic targets in cholestatis, we determined their expression in individual cell types of the mouse liver in normal and cholestatic conditions. Hepatocytes, cholangiocytes, hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were isolated from the liver of mice with acute or chronic cholestasis (i...
April 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28355206/hepatic-mdr3-expression-impacts-lipid-homeostasis-and-susceptibility-to-inflammatory-bile-duct-obstruction-in-neonates
#4
Alexandra N Carey, Wujuan Zhang, Kenneth D R Setchell, Julia R Simmons, Tiffany Shi, Celine S Lages, Mary Mullen, Kaitlin Carroll, Rebekah Karns, Kazuhiko Bessho, Rachel Sheridan, Xueheng Zhao, Susanne N Weber, Alexander G Miethke
BackgroundHeterozygous mutations in the gene ABCB4, encoding the phospholipid floppase MDR3 (Mdr2 in mice), are associated with various chronic liver diseases. Here we hypothesize that reduced ABCB4 expression predisposes to extrahepatic biliary atresia (EHBA).MethodsLivers from neonatal wild-type (wt) and heterozygous Mdr2-deficient mice were subjected to mass spectrometry-based lipidomics and RNA sequencing studies. Following postnatal infection with rhesus rotavirus (RRV), liver immune responses and EHBA phenotype were assessed...
May 3, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28347352/combined-target-site-kdr-mutations-play-a-primary-role-in-highly-pyrethroid-resistant-phenotypes-of-aedes-aegypti-from-saudi-arabia
#5
Ashwaq M Al Nazawi, Jabir Aqili, Mohammed Alzahrani, Philip J McCall, David Weetman
BACKGROUND: Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28274756/common-genetic-variation-and-risk-of-gallbladder-cancer-in-india-a-case-control-genome-wide-association-study
#6
Sharayu Mhatre, Zhaoming Wang, Rajini Nagrani, Rajendra Badwe, Shubhada Chiplunkar, Balraj Mittal, Saurabh Yadav, Haoyu Zhang, Charles C Chung, Prachi Patil, Stephen Chanock, Rajesh Dikshit, Nilanjan Chatterjee, Preetha Rajaraman
BACKGROUND: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer. METHODS: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20-80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28249287/the-role-of-inflammation-in-the-mechanisms-of-bile-acid-induced-liver-damage
#7
Shi-Ying Cai, James L Boyer
BACKGROUND: The mechanism by which bile acids induce liver injury in cholestasis remains controversial. Although high levels of bile acids are toxic when applied to liver cells, the level of toxic bile acids in the liver of most cholestatic animals and patients is <10 μM, indicating there must be alternative mechanisms. Recent studies suggest that the inflammatory response may play an important role in bile acid-induced liver injury, as pro-inflammatory cytokine expression is stimulated by bile acids in mouse hepatocyte cultures...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28223721/current-and-future-therapies-for-inherited-cholestatic-liver-diseases
#8
REVIEW
Wendy L van der Woerd, Roderick Hj Houwen, Stan Fj van de Graaf
Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2)...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28220208/abcb4-missense-mutations-d243a-k435t-g535d-i490t-r545c-and-s978p-significantly-impair-the-lipid-floppase-and-likely-predispose-to-secondary-pathologies-in-the-human-population
#9
Edward J Andress, Michael Nicolaou, Farrell McGeoghan, Kenneth J Linton
Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28194423/effects-of-liver-fibrosis-progression-on-tissue-relaxation-times-in-different-mouse-models-assessed-by-ultrahigh-field-magnetic-resonance-imaging
#10
Andreas Müller, Katrin Hochrath, Jonas Stroeder, Kanishka Hittatiya, Günther Schneider, Frank Lammert, Arno Buecker, Peter Fries
Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2(⁎) may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2(⁎) in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2(⁎)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28184004/ets-proto-oncogene-1-transcriptionally-up-regulates-the-cholangiocyte-senescence-associated-protein-cyclin-dependent-kinase-inhibitor-2a
#11
Steven P O'Hara, Patrick L Splinter, Christy E Trussoni, Maria J Lorenzo Pisarello, Lorena Loarca, Noah S Splinter, Bryce F Schutte, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory cholangiopathy (disease of the bile ducts) of unknown pathogenesis. We reported that cholangiocyte senescence features prominently in PSC and that neuroblastoma RAS viral oncogene homolog (NRAS) is activated in PSC cholangiocytes. Additionally, persistent microbial insult (e.g. LPSs) induces cyclin-dependent kinase inhibitor 2A (CDKN2A/p16(INK4a)) expression and senescence in cultured cholangiocytes in an NRAS-dependent manner. However, the molecular mechanisms involved in LPS-induced cholangiocyte senescence and NRAS-dependent regulation of CDKN2A remain unclear...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28178654/hepatitis-b-virus-surface-proteins-accelerate-cholestatic-injury-and-tumor-progression-in-abcb4-knockout-mice
#12
Daniel Zahner, Hannah Glimm, Tomomitsu Matono, Yuri Churin, Diran Herebian, Ertan Mayatepek, Kernt Köhler, Stefan Gattenlöhner, Anne Stinn, Annette Tschuschner, Martin Roderfeld, Elke Roeb
Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4-/- and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28127842/hepatocarcinogenesis-in-multidrug-resistant-p-glycoprotein-3-deficiency
#13
Mukul Vij, Naresh P Shanmugam, Mettu Srinivas Reddy, Sanjay Govil, Mohamed Rela
MDR3 is a hepatocyte canalicular membrane protein encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine into bile. Severe MDR 3 deficiency typically presents during early childhood with chronic cholestasis evolving to cirrhosis and portal hypertension, requiring liver transplantation. Herein, we report a case of severe MDR3 deficiency in a male child diagnosed with negative MDR3 immunostaining in hepatic canaliculi who underwent LDLT at our centre. We also describe single incidentally detected early well-differentiated HCC in the explant liver...
May 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28012258/functional-defect-of-variants-in-the-adenosine-triphosphate-binding-sites-of-abcb4-and-their-rescue-by-the-cystic-fibrosis-transmembrane-conductance-regulator-potentiator-ivacaftor-vx-770
#14
Jean-Louis Delaunay, Alix Bruneau, Brice Hoffmann, Anne-Marie Durand-Schneider, Véronique Barbu, Emmanuel Jacquemin, Michèle Maurice, Chantal Housset, Isabelle Callebaut, Tounsia Aït-Slimane
ABCB4 (MDR3) is an adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene are responsible for several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), a rare disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ABCB4 missense variations that reside in the highly conserved motifs of ABC transporters, involved in ATP binding...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28010888/dose-dependent-effects-of-morphine-on-lipopolysaccharide-lps-induced-inflammation-and-involvement-of-multixenobiotic-resistance-mxr-transporters-in-lps-efflux-in-teleost-fish
#15
Hélène Mottaz, Rene Schönenberger, Stephan Fischer, Rik I L Eggen, Kristin Schirmer, Ksenia J Groh
Opioid drugs, such as morphine (MO), detected in aquatic environments worldwide, may harm fish due to their semi-persistence and ability to potently interact with molecular targets conserved across vertebrates. Here, we established a waterborne bacterial lipopolysaccharide (LPS) challenge assay with zebrafish embryos as a model to investigate chemically-induced disruption of the innate immune system, and used it to study the effects of MO exposure. Exposure to 1 mg/L MO resulted in pronounced immunosuppression, reflected in downregulation of several inflammation-related genes, including myd88, trif, traf6, p38, nfκb2, il-1β, il-8 and ccl34a...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27995969/biliary-phospholipids-sustain-enterocyte-proliferation-and-intestinal-tumor-progression-via-nuclear-receptor-lrh1-in-mice
#16
Michele Petruzzelli, Elena Piccinin, Claudio Pinto, Claudia Peres, Elena Bellafante, Antonio Moschetta
The proliferative-crypt compartment of the intestinal epithelium is enriched in phospholipids and accumulation of phospholipids has been described in colorectal tumors. Here we hypothesize that biliary phospholipid flow could directly contribute to the proliferative power of normal and dysplastic enterocytes. We used Abcb4(-/-) mice which lack biliary phospholipid secretion. We first show that Abcb4(-/-) mice are protected against intestinal tumorigenesis. At the molecular level, the transcriptional activity of the nuclear receptor Liver Receptor Homolog-1 (Lrh1) is reduced in Abcb4(-/-) mice and its re-activation re-establishes a tumor burden comparable to control mice...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939613/pharmacotoxicology-of-clinically-relevant-concentrations-of-obeticholic-acid-in-an-organotypic-human-hepatocyte-system
#17
A Dash, R A Figler, B R Blackman, S Marukian, M S Collado, M J Lawson, S A Hoang, A J Mackey, D Manka, B K Cole, R E Feaver, A J Sanyal, B R Wamhoff
Nonalcoholic steatohepatitis (NASH) is an emerging health crisis with no approved therapies. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, shows promise in NASH trials. However, the precise mechanisms mediating OCA effects and impact on cholesterol metabolism are not fully understood. We explored the pharmaco-toxicological effects of OCA on patho-physiological pathways in hepatocytes using a previously described perfused organotypic liver system that allows culture in near-physiological insulin/glucose milieus, and exhibits drug responses at clinically-relevant concentrations...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27898169/cross-sectional-analysis-of-progressive-familial-intrahepatic-cholestasis-in-puerto-rican-children
#18
Dellys M Soler, Antonio I Del Valle, David Fernandez-Lube, Benjamin L Shneider
OBJECTIVE: Specific inherited disorders may be more common in island communities. Prior case reports suggest that cholestatic liver diseases may constitute a group of these inherited disorders in Puerto Rico. A cross-sectional survey of liver diseases in children was conducted to assess this hypothesis. METHODS: A cross-sectional analysis was performed in patients with chronic cholestasis at "Hospital Pediátrico Universitario" in San Juan, Puerto Rico. Ten potential participants with high gamma-glutamyl transpeptidase (GGTP) cholestasis were identified...
December 2016: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#19
Ursula J Lemberger, Claudia D Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27883295/identification-of-novel-snps-associated-with-risk-and-prognosis-in-patients-with-castration-resistant-prostate-cancer
#20
Tristan M Sissung, John Deeken, Crystal R Leibrand, Douglas K Price, Sheryl Ehrlich, Seth M Steinberg, David J Liewehr, William Dahut, William D Figg
AIM: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). MATERIALS & METHODS: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. RESULTS: No relation to risk was found...
December 2016: Pharmacogenomics
keyword
keyword
44922
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"