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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28428350/targeted-inactivation-of-copper-transporter-atp7b-in-hepatocytes-causes-liver-steatosis-and-obesity-in-mice
#1
Abigael Muchenditsi, Haojun Yang, James P Hamilton, Lahari Koganti, Franck Housseau, Lisa Aronov, Hongni Fan, Hannah Pierson, Ashima Bhattacharjee, Robert C Murphy, Cynthia L Sears, James J Potter, Clavia Ruth Wooton-Kee, Svetlana Lutsenko
The copper transporter ATP7B is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7bΔ(Hep) mice accumulate copper in the liver, have elevated urinary copper, lack holo-ceruloplasmin, but show no liver disease for up to 30 weeks...
April 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408644/human-derived-gut-microbiota-modulates-colonic-secretion-in-mice-by-regulating-5-ht3-receptor-expression-via-acetate-production
#2
Yogesh Bhattarai, Bradley A Schmidt, David R Linden, Eric D Larson, Madhusudan Grover, Arthur Beyder, Gianrico Farrugia, Purna C Kashyap
Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and a paracrine messenger in the gastrointestinal (GI) tract, regulates intestinal secretion by its action primarily on 5-HT3 and 5-HT4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study we determine if human-derived gut microbiota affect host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age matched Swiss Webster germ free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408643/gastrin-induces-parathyroid-hormone-like-hormone-expression-in-gastric-parietal-cells
#3
Asma Al Menhali, Theresa M Keeley, Elise S Demitrack, Linda C Samuelson
Parietal cells play a fundamental role in stomach maintenance, not only by creating a pathogen-free environment through the production of gastric acid, but also by secreting growth factors important for homeostasis of the gastric epithelium. The gastrointestinal hormone gastrin is known to be a central regulator of both parietal cell function and gastric epithelial cell proliferation and differentiation. Our previous gene expression profiling studies of mouse stomach identified parathyroid hormone-like hormone (PTHLH) as a potential gastrin-regulated gastric growth factor...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408642/elevated-intrabolus-pressure-identifies-obstructive-processes-when-integrated-relaxation-pressure-is-normal-on-esophageal-high-resolution-manometry
#4
Farhan Quader, Chanakyaram Reddy, Amit Patel, C Prakash Gyawali
BACKGROUND: Elevated integrated relaxation pressure (IRP) on esophageal high resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). AIM: To determine if intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. METHODS: In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408641/gastroparesis-and-lipid-metabolism-associated-dysbiosis-in-wistar-kyoto-rats
#5
Julie E Dalziel, Karl Fraser, Wayne Young, Catherine M Lloyd-West, Shalome A Bassett, Nicole C Roy
Altered gastric accommodation and intestinal morphology suggests impaired gastrointestinal (GI) transit may occur in the Wistar Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague Dawley (SD) rats under basal conditions, and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor: gastric emptying (GE; 4 h), small intestine (SI) transit (9 h) and large intestine transit (12 h)...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#6
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385694/phosphatidylcholine-transfer-protein-stard2-promotes-microvesicular-steatosis-and-liver-injury-in-murine-experimental-steatohepatitis
#7
Hayley Tenielle Nicholls, Jason L Hornick, David E Cohen
Mice fed a methionine and choline deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholine among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385693/expression-and-localization-of-vpac1-the-major-receptor-of-vasoactive-intestinal-peptide-along-the-length-of-the-intestine
#8
Dulari Jayawardena, Grace Guzman, Ravinder K Gill, Waddah A Alrefai, Hayat Onyuksel, Pradeep K Dudeja
Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G- protein coupled receptors and VPAC1 is the key receptor responsible for majority of VIP's biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its sub cellular localization in intestinal epithelial cells has not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP based therapies can be targeted to specific regions of the intestine...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360031/intermediate-filament-proteins-of-digestive-organs-physiology-and-pathophysiology
#9
M Bishr Omary
Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the 3 major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation-state expression, and association with >80 human diseases when mutated. While most IF mutations cause disease, mutations in simple epithelial keratins 8, 18 or 19, or in lamin A/C predispose to liver disease with or without other tissue manifestations...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360030/old-and-new-models-for-studying-host-microbe-interactions-in-health-and-disease-c-difficile-as-an-example
#10
Vincent Bensan Young
There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can study the host-microbe interaction...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360029/ursodeoxycholic-acid-and-lithocholic-acid-exert-anti-inflammatory-actions-in-the-colon
#11
Joseph B J Ward, Natalia K Lajczak, Orlaith B Kelly, Aoife M O'Dwyer, Ashwini K Giddam, Joan N Ní Gabhainn, Placido Franco, Murtaza M Tambuwala, Caroline A Jefferies, Simon Keely, Aldo Roda, Stephen Joseph Keely
Inflammatory bowel diseases (IBD) are a group of common and debilitating chronic intestinal disorders for which currently-available therapies are often unsatisfactory. The naturally-occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. Here, we aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360028/detection-of-human-elastase-isoforms-by-the-schebo-pancreatic-elastase-1-test
#12
Anna Zsofia Toth, Andras Szabo, Eszter Hegyi, Peter Hegyi, Miklos Sahin-Toth
Determination of fecal pancreatic elastase content by ELISA is a reliable, non-invasive clinical test for assessing exocrine pancreatic function. Despite the widespread use of commercial tests, their exact molecular targets remain poorly characterized. This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally-occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases we found that the test specifically measured chymotrypsin-like elastases 3A and 3B (CELA3A and CELA3B) while CELA2A was not detected...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336550/the-effect-of-intravenous-corticotropin-releasing-hormone-administration-on-esophageal-sensitivity-and-motility-in-health
#13
Charlotte Broers, Chloé Melchior, Lukas Van Oudenhove, Tim Vanuytsel, Brecht Van Houtte, Charlotte Scheerens, Nathalie Rommel, Jan F Tack, Ans Pauwels
BACKGROUND: Esophageal hypersensitivity is important in gastro-esophageal reflux disease (GERD) patients refractory to acid-suppressive therapy. Stress affects visceral sensitivity and exacerbates heartburn in GERD. Peripheral CRH is a key mediator of the gut stress response. We hypothesize that CRH increases esophageal sensitivity and alters esophageal motility in health. METHODS: Esophageal sensitivity to thermal, mechanical, electrical and chemical stimuli was assessed in 14 healthy subjects after placebo or CRH (100μg IV)...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336549/eavk-segment-c-sequence-confers-ca-2-dependent-changes-to-the-kinetics-of-full-length-human-ano1
#14
Peter R Strege, Simon J Gibbons, Amelia Mazzone, Cheryl E Bernard, Arthur Beyder, Gianrico Farrugia
Anoctamin1 (Ano1, TMEM16A) is a calcium-activated chloride channel specifically expressed in interstitial cells of Cajal (ICC) of the gastrointestinal (GI) tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full length human Ano1 sequence includes an additional exon, exon "0," at the N-terminus. Ano1 with exon "0" (Ano1(0)) had a lower EC50 for intracellular calcium ([Ca(2+)]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter ICl at low [Ca(2+)]i Exon 13 is expressed in 75-100% of Ano1 transcripts in most human tissues but only 25% in human stomach...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336548/nutrient-sensing-by-absorptive-and-secretory-progenies-of-small-intestinal-stem-cells
#15
Kunihiro Kishida, Sarah C Pearce, Shiyan Yu, Nan Gao, Ronaldo P Ferraris
Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown, hence we hypothesized that progenitor stem cells (ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling, differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336547/glycans-in-the-intestinal-peptide-transporter-pept1-contribute-to-function-and-protect-from-proteolysis
#16
Tamara Stelzl, Kerstin Elisabeth Geillinger-Kästle, Jürgen Stolz, Hannelore Daniel
Despite the fact that many membrane proteins carry extracellular glycans, little is known about whether the glycan chains also affect protein function. We recently demonstrated that the proton-coupled oligopeptide transporter 1 (PEPT1) in the intestine is glycosylated at six asparagine residues (N50, N406, N439, N510, N515, N532). Mutagenesis-induced disruption of the individual N-glycosylation site N50, which is highly conserved among mammals, was detected to significantly enhance the PEPT1 mediated inward transport of peptides...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336546/barrett-s-metaplasia-develops-from-cellular-reprograming-of-esophageal-squamous-epithelium-due-to-gastroesophageal-reflux
#17
Carlos D Minacapelli, Manisha Bajpai, Xin Geng, Christina L Cheng, Abhishek A Chouthai, Rhonda F Souza, Stuart Jon Spechler, Kiron M Das
OBJECTIVE: Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting cellular origin of BM from reprograming or trans-commitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile exposure using an in vitro cell culture model. DESIGN: The hTERT-immortalized NES cell line, NES-B10T, was exposed 5 min/day to Acid and Bile (A+B) mixture for 30 weeks...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336545/changes-in-intestinal-microbiota-composition-and-metabolism-coincide-with-increased-intestinal-permeability-in-young-adults-under-prolonged-physiologic-stress
#18
J Philip Karl, Lee M Margolis, Elisabeth H Madslien, Nancy E Murphy, John W Castellani, Yngvar Gundersen, Allison V Hoke, Michael W Levangie, Raina Kumar, Nabarun Chakraborty, Aarti Gautam, Rasha Hammamieh, Svein Martini, Scott J Montain, Stefan M Pasiakos
The magnitude, temporal dynamics, and physiologic effects of intestinal microbiome responses to physiologic stress are poorly characterized. This study used a systems biology approach and multiple-stressor military training environment to determine the effects of physiologic stress on intestinal microbiota composition and metabolic activity, and intestinal permeability (IP). 73 Soldiers were provided three rations/d with or without protein- or carbohydrate-based supplements during a four day cross-country ski march (STRESS)...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336544/high-resolution-anatomical-correlation-of-cyclic-motor-patterns-in-the-human-colon-evidence-of-a-rectosigmoid-brake
#19
Anthony Y Lin, Peng Du, Philip G Dinning, John W Arkwright, Jozef P Kamp, Leo K Cheng, Ian P Bissett, Gregory O'Grady
Colonic cyclic motor patterns (CMPs) have been hypothesized to act as a brake to limit rectal filling. However, the spatiotemporal profile of CMPs, including anatomical origins and distributions, remains unclear. This study characterized colonic CMPs using high-resolution (HR) manometry (72 sensors, 1 cm resolution) and their relationship with proximal antegrade propagating events. Nine healthy volunteers were recruited. Recordings were performed over 4 h, with a 700 kcal meal given after 2 h. Propagating events were visually identified and analyzed by pattern, origin, amplitude, extent of propagation, velocity, and duration...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28302598/helminths-in-the-gastrointestinal-tract-as-modulators-of-immunity-and-pathology
#20
Fumi Varyani, John O Fleming, Rick M Maizels
Helminth parasites are highly prevalent in many low- and middle-income countries, in which inflammatory bowel disease and other immunopathologies are less frequent than in the developed world. Many of the most common helminths establish in the gastrointestinal tract, and can exert counter-inflammatory influences on the host immune system. For these reasons, interest has arisen in how parasites may ameliorate intestinal inflammation and whether these organisms, or products they release, could offer future therapies for immune disorders...
March 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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