Epithelial barrier function in vivo is sustained despite gaps in epithelial layers.

Abstract:

BACKGROUND & AIMS:Epithelial cells of the small intestine migrate to the tip of the villus at which they are shed. It is not understood how the intestinal barrier is maintained during this high cell turnover. The aim of this study was to use high-resolution in vivo light microscopy to investigate the mechanism of epithelial shedding and the site of the permeability barrier during cell shedding. METHODS:A laparotomy was performed on anesthetized mice, and a segment of small intestine was opened. The exposed epithelial surface of the intestine was imaged by multiphoton microscopy. Nuclei, cytosol, and cell membranes were imaged using the dyes Hoescht 33258, BCECF, a transgenically expressed fluorescent protein, and the membrane dye DiI. The fluorescent caspase substrate PhiPhiLux was used to detect apoptosis. RESULTS:In the epithelial monolayer, gaps were observed that lacked nuclei or cytosol but appeared to be filled with an impermeable substance. Studies with membrane impermeant fluorophores (Lucifer Yellow and Alexa-dextran) showed that the impermeable substance completely fills the void left by the absent cell. Only a fraction of gaps have either ZO-1 staining or cytoplasmic extensions from neighboring cells at the basal pole. Time-lapse studies reveal that cell shedding results in genesis of a gap and that shedding usually occurs prior to detectable cellular activation of caspase 3 or nuclear condensation. CONCLUSIONS:Results suggest that epithelial barrier function is sustained at the apical pole of the epithelial layer, despite discontinuities in the cellular layer.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Watson AJ,Chu S,Sieck L,Gerasimenko O,Bullen T,Campbell F,McKenna M,Rose T,Montrose MH

doi

10.1053/j.gastro.2005.06.015

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

902-12

issue

3

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(05)01117-0

journal_volume

129

pub_type

杂志文章
  • From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome.

    abstract:BACKGROUND & AIMS:Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. METHODS:Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolong...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2020.08.053

    authors: Vu K,Lou W,Tun HM,Konya TB,Morales-Lizcano N,Chari RS,Field CJ,Guttman DS,Mandal R,Wishart DS,Azad MB,Becker AB,Mandhane PJ,Moraes TJ,Lefebvre DL,Sears MR,Turvey SE,Subbarao P,Scott JA,Kozyrskyj AL

    更新日期:2021-01-01 00:00:00

  • Chronic enteric salmonella infection in mice leads to severe and persistent intestinal fibrosis.

    abstract:BACKGROUND & AIMS:Intestinal fibrosis and stricture formation are serious complications of Crohn's disease, often requiring surgical intervention. Unfortunately, the mechanisms underlying intestinal fibrosis development are poorly understood, in part because of the lack of relevant animal models. Here, we present a nov...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2007.12.043

    authors: Grassl GA,Valdez Y,Bergstrom KS,Vallance BA,Finlay BB

    更新日期:2008-03-01 00:00:00

  • Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

    abstract::Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical a...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2017.11.009

    authors: Lupinacci RM,Goloudina A,Buhard O,Bachet JB,Maréchal R,Demetter P,Cros J,Bardier-Dupas A,Collura A,Cervera P,Scriva A,Dumont S,Hammel P,Sauvanet A,Louvet C,Delpéro JR,Paye F,Vaillant JC,André T,Closset J,Emile JF

    更新日期:2018-03-01 00:00:00

  • Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation.

    abstract:BACKGROUND & AIMS:Cell stress signaling pathways result in phosphorylation of the eukaryotic translation initiation factor 2 subunit alpha (EIF2S1 or EIF2A), which affects regulation of protein translation. Translation reprogramming mitigates stress by activating pathways that result in autophagy and cell death, to eli...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2017.12.016

    authors: Roy S,Esmaeilniakooshkghazi A,Patnaik S,Wang Y,George SP,Ahrorov A,Hou JK,Herron AJ,Sesaki H,Khurana S

    更新日期:2018-04-01 00:00:00

  • Low risk of colorectal cancer and advanced adenomas more than 10 years after negative colonoscopy.

    abstract:BACKGROUND & AIMS:Screening colonoscopy is an effective method to reduce the incidence of and mortality from colorectal cancer (CRC). There is little empirical evidence available about the optimal interval for screening, making this a subject of debate. We associated the prevalence of advanced colorectal neoplasms with...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2009.10.054

    authors: Brenner H,Haug U,Arndt V,Stegmaier C,Altenhofen L,Hoffmeister M

    更新日期:2010-03-01 00:00:00

  • Long-term survival in patients with hereditary hemochromatosis.

    abstract:BACKGROUND & AIMS:The course of hereditary hemochromatosis may depend on the degree of iron overload and the time of therapeutic intervention. This analysis evaluates the impact of early diagnosis and iron removal on survival and complications in hereditary hemochromatosis. METHODS:A Cohort of 251 patients with hemoch...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.1996.v110.pm8613000

    authors: Niederau C,Fischer R,Pürschel A,Stremmel W,Häussinger D,Strohmeyer G

    更新日期:1996-04-01 00:00:00

  • Role of fat maldigestion in pathogenesis of steatorrhea in ileal resection. Fat digestion after two sequential test meals with and without cholestyramine.

    abstract::To clarify the role of fat maldigestion in the pathogenesis of steatorrhea in patients with ileal resection the total and aqueous phase concentrations of bile acid and fatty acid were characterized in 8 such patients (5 patients with small ileal resection, bile acid diarrhea, and steatorrhea less than 20 g per day; 3 ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Poley JR,Hofmann AF

    更新日期:1976-07-01 00:00:00

  • Genetic variation in myosin IXB is associated with ulcerative colitis.

    abstract:BACKGROUND & AIMS:Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role f...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究

    doi:10.1053/j.gastro.2006.09.011

    authors: van Bodegraven AA,Curley CR,Hunt KA,Monsuur AJ,Linskens RK,Onnie CM,Crusius JB,Annese V,Latiano A,Silverberg MS,Bitton A,Fisher SA,Steinhart AH,Forbes A,Sanderson J,Prescott NJ,Strachan DP,Playford RJ,Mathew CG,Wijm

    更新日期:2006-12-01 00:00:00

  • Direct-Acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-Induced Cryoglobulinemia Vasculitis.

    abstract:BACKGROUND & AIMS:Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular i...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2017.02.037

    authors: Comarmond C,Garrido M,Pol S,Desbois AC,Costopoulos M,Le Garff-Tavernier M,Si Ahmed SN,Alric L,Fontaine H,Bellier B,Maciejewski A,Rosenzwajg M,Klatzmann D,Musset L,Poynard T,Cacoub P,Saadoun D

    更新日期:2017-06-01 00:00:00

  • Effects of luminal glucose versus nonnutritive infusates on jejunal mass and absorption in the rat.

    abstract::These studies were designed to better understand the effects of luminal nutrition on intestinal mass and function. Parenterally nourished rats received a midjejunal infusion of either 0.9% saline, 10% glucose, 10% 3-O-methyl glucose, or 30% glucose. A fifth group underwent sham operation. After 7 days, intestinal mass...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Richter GC,Levine GM,Shiau YF

    更新日期:1983-11-01 00:00:00

  • What Is Needed to Eliminate Hepatitis B Virus and Hepatitis C Virus as Global Health Threats.

    abstract::Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause 1.3 million deaths annually. To prevent more than 7 million deaths by 2030, the World Health Organization set goals to eliminate HBV and HCV, defined as a 90% reduction in new infections and a 65% reduction in deaths, and prevent more than 7 million related dea...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2018.10.048

    authors: Ward JW,Hinman AR

    更新日期:2019-01-01 00:00:00

  • AGA Clinical Practice Update on Endoscopic Therapies for Non-Variceal Upper Gastrointestinal Bleeding: Expert Review.

    abstract:DESCRIPTION:The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and best practice advice statements regarding the use of endoscopic therapies in treating patients with non-variceal upper gastrointestinal bleeding. METHODS:This expert...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2020.05.095

    authors: Mullady DK,Wang AY,Waschke KA

    更新日期:2020-09-01 00:00:00

  • Risk of colorectal cancer in patients prescribed statins, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitors: nested case-control study.

    abstract:BACKGROUND AND AIMS:Several studies suggest that statins prevent some cancers, with one study finding a 47% reduction in colorectal cancer risk after >or=5 years of regular use. METHODS:A nested case-control study was conducted within 454 general practices in the United Kingdom using the QRESEARCH database. Cases with...

    journal_title:Gastroenterology

    pub_type: 杂志文章,多中心研究

    doi:10.1053/j.gastro.2007.05.023

    authors: Vinogradova Y,Hippisley-Cox J,Coupland C,Logan RF

    更新日期:2007-08-01 00:00:00

  • Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis.

    abstract:BACKGROUND & AIMS:The anti-cancer effects of vegetables and fruit have been investigated extensively, but the association between vegetable and fruit consumption and risk of hepatocellular carcinoma (HCC) has not been quantified. We performed a meta-analysis of observational studies to clarify the association. METHODS...

    journal_title:Gastroenterology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1053/j.gastro.2014.08.005

    authors: Yang Y,Zhang D,Feng N,Chen G,Liu J,Chen G,Zhu Y

    更新日期:2014-11-01 00:00:00

  • Occurrence of specific secretory immunoglobulin A in bile after inoculation of Giardia lamblia trophozoites into rat duodenum.

    abstract::We studied the appearance of specific secretory immunoglobulin A (IgA) antibody in bile after inoculation of live Giardia lamblia trophozoites into rat intestine. Serial bile specimens collected before and after inoculation of trophozoites were assayed for IgA antibodies by indirect immunofluorescence. Secretory IgA a...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Loftness TJ,Erlandsen SL,Wilson ID,Meyer EA

    更新日期:1984-11-01 00:00:00

  • Independent influences of body mass and gastric volumes on satiation in humans.

    abstract:BACKGROUND & AIMS:We assessed the association of body mass and gastric volumes (fasting and postprandial) with satiation and postprandial symptoms. METHODS:Healthy obese and nonobese subjects underwent measurement of caloric intake at maximum satiation; postprandial symptoms were measured with visual analogue scales 3...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2003.11.007

    authors: Delgado-Aros S,Cremonini F,Castillo JE,Chial HJ,Burton DD,Ferber I,Camilleri M

    更新日期:2004-02-01 00:00:00

  • A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice.

    abstract:BACKGROUND & AIMS:Cystic fibrosis transmembrane regulator (CFTR) gene mutations are associated with pancreatic insufficiency and pancreatitis. Chronic pancreatitis, including cystic fibrosis-related disease, may exist as a continuum between acute and chronic disease and may manifest as recurrent pain. We hypothesized t...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/j.gastro.2005.05.059

    authors: Dimagno MJ,Lee SH,Hao Y,Zhou SY,McKenna BJ,Owyang C

    更新日期:2005-08-01 00:00:00

  • Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study.

    abstract:BACKGROUND & AIMS:Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. METHODS:We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulc...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2005.03.026

    authors: Hung LC,Ching JY,Sung JJ,To KF,Hui AJ,Wong VW,Leong RW,Chan HL,Wu JC,Leung WK,Lee YT,Chung SC,Chan FK

    更新日期:2005-06-01 00:00:00

  • Functional gastroduodenal disorders.

    abstract::A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gast...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2005.11.059

    authors: Tack J,Talley NJ,Camilleri M,Holtmann G,Hu P,Malagelada JR,Stanghellini V

    更新日期:2006-04-01 00:00:00

  • Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology.

    abstract:BACKGROUND & AIMS:Guidelines for the management of venous thromboembolism (VTE) from the American College of Chest Physicians do not address patients with inflammatory bowel disease (IBD), a group with a high risk of both VTE and gastrointestinal bleeding. We present recommendations for the prevention and treatment of ...

    journal_title:Gastroenterology

    pub_type: 共识发展会议,杂志文章,评审

    doi:10.1053/j.gastro.2014.01.042

    authors: Nguyen GC,Bernstein CN,Bitton A,Chan AK,Griffiths AM,Leontiadis GI,Geerts W,Bressler B,Butzner JD,Carrier M,Chande N,Marshall JK,Williams C,Kearon C

    更新日期:2014-03-01 00:00:00

  • REG Ialpha protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer.

    abstract:BACKGROUND & AIMS:Although a significant amount of regenerating gene (REG) Ialpha protein is present not only in normal gastric mucosa but also in gastric cancer tissues, its pathophysiologic role in gastric cancer development remains unclear. We investigated REG Ialpha protein expression in early gastric cancers, and ...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2004.12.045

    authors: Sekikawa A,Fukui H,Fujii S,Takeda J,Nanakin A,Hisatsune H,Seno H,Takasawa S,Okamoto H,Fujimori T,Chiba T

    更新日期:2005-03-01 00:00:00

  • Compositional and functional features of the gastrointestinal microbiome and their effects on human health.

    abstract::The human gastrointestinal tract contains distinct microbial communities that differ in composition and function based on their location, as well as age, sex, race/ethnicity, and diet of their host. We describe the bacterial taxa present in different locations of the GI tract, and their specific metabolic features. Th...

    journal_title:Gastroenterology

    pub_type: 杂志文章,评审

    doi:10.1053/j.gastro.2014.01.052

    authors: Hollister EB,Gao C,Versalovic J

    更新日期:2014-05-01 00:00:00

  • Amino terminal gastrin fragment in serum of Zollinger-Ellison syndrome patients.

    abstract::In addition to the previously described molecular forms of gastrin, a new component has been found in high concentrations in the serum of 6 patients with Zollinger-Ellison syndrome. Serum was fractionated by gel filtration, and ion exchange chromatography, and the new component was identified in eluates by radioimmuno...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Dockray GJ,Walsh JH

    更新日期:1975-02-01 00:00:00

  • Inflammatory bowel disease and the risk of fracture.

    abstract:BACKGROUND & AIMS:Although patients with inflammatory bowel disease (IBD) have reduced bone mass, there is controversy whether there is an increased risk of fracture. This study examines the risk of fracture and its predictors in patients with IBD. METHODS:In a primary care- based nested case-control study, 231,778 fr...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2003.09.027

    authors: van Staa TP,Cooper C,Brusse LS,Leufkens H,Javaid MK,Arden NK

    更新日期:2003-12-01 00:00:00

  • Diagnostic usefulness of plasma carcinoembryonic antigen levels in acute and chronic liver disease.

    abstract::Raised plasma carcinoembryonic antigen (CEA) levels were found in over 90% of 71 patients with chronic liver disease and 50% of 16 patients with acute liver damage. Levels increasing chronicity and clinical severity of disease. In individual patients, the plasma CEA level fluctuated with the clinical condition. Persis...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Bullen AW,Losowsky MS,Carter S,Patel S,Neville AM

    更新日期:1977-10-01 00:00:00

  • Crohn's disease involving the colon: an audit of clinical management.

    abstract::This paper describes the clinical management of 204 patients with Crohn's disease involving the colon who have been reviewed regularly for many years. The results have been analyzed to define the morbidity, mortality, and long term prognosis of the disorder. Despite a high morbidity, the long term prognosis is good. A...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:

    authors: Allan R,Steinberg DM,Williams JA,Cooke WT

    更新日期:1977-10-01 00:00:00

  • The importance of cycling of blood alcohol levels in the pathogenesis of experimental alcoholic liver disease in rats.

    abstract:BACKGROUND & AIMS:Rats fed ethanol at a constant rate through a permanent intragastric cannula have a regular fluctuation in blood alcohol level (BAL) and urine alcohol level (UAL). The level of ethanol peaks every 6-10 days. The question is how the liver differs at the peaks and troughs of the UAL cycle. Hypoxic injur...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/gast.2002.34177

    authors: Bardag-Gorce F,French BA,Li J,Riley NE,Yuan QX,Valinluck V,Fu P,Ingelman-Sundberg M,Yoon S,French SW

    更新日期:2002-07-01 00:00:00

  • The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome.

    abstract:BACKGROUND & AIMS:Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid kappa receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine, a potent and selective kappa...

    journal_title:Gastroenterology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0016-5085(99)70226-x

    authors: Delvaux M,Louvel D,Lagier E,Scherrer B,Abitbol JL,Frexinos J

    更新日期:1999-01-01 00:00:00

  • PPARD and Interferon Gamma Promote Transformation of Gastric Progenitor Cells and Tumorigenesis in Mice.

    abstract:BACKGROUND & AIMS:The peroxisome proliferator-activated receptor delta (PPARD) regulates cell metabolism, proliferation, and inflammation and has been associated with gastric and other cancers. Villin-positive epithelial cells are a small population of quiescent gastric progenitor cells. We expressed PPARD from a villi...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1053/j.gastro.2019.03.018

    authors: Zuo X,Deguchi Y,Xu W,Liu Y,Li HS,Wei D,Tian R,Chen W,Xu M,Yang Y,Gao S,Jaoude JC,Liu F,Chrieki SP,Moussalli MJ,Gagea M,Sebastian MM,Zheng X,Tan D,Broaddus R,Wang J,Ajami NJ,Swennes AG,Watowich SS,Shureiqi

    更新日期:2019-07-01 00:00:00

  • Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis.

    abstract::We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median c...

    journal_title:Gastroenterology

    pub_type: 杂志文章

    doi:10.1016/0016-5085(86)90682-7

    authors: Lunzer M,Barnes P,Byth K,O'Halloran M

    更新日期:1986-10-01 00:00:00