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    Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy.

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    Authors
    Kiesslich, Ralf
    Goetz, Martin
    Angus, Elizabeth M
    Hu, Qiuping
    Guan, Yanfang
    Potten, Christopher S
    Allen, Terence D
    Neurath, Markus F
    Shroyer, Noah F
    Montrose, Marshall H
    Watson, Alastair
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    Affiliation
    I Medical Clinic, University of Mainz, Mainz, Germany.
    Issue Date
    2007-12
    
    Metadata
    Show full item record
    Abstract
    BACKGROUND & AIMS: Confocal endomicroscopy is an emerging technology that poses the endoscopist with challenges for identifying epithelial structures in the human intestine. We have shown previously that the murine intestinal epithelium is punctuated by gaps caused by cell shedding. The goals of this study were to determine if confocal endomicroscopy could resolve the presence of human epithelial gaps and whether a proinflammatory cytokine could increase cell shedding. METHODS: Intestinal mucosa was imaged after staining with acriflavine. Confocal endomicroscopy of 17 patients yielded 6277 images from the human terminal ileum and rectum. Results were validated by parallel studies of anesthetized mice (wild-type and Math1(DeltaIntestine)) using rigid confocal probe microscopy, 2-photon/confocal microscopy, and scanning electron microscopy. RESULTS: Human terminal ileal and rectal epithelium revealed unstained areas with the diameter of an individual epithelial cell, with 2 distinct morphologies. One had a "target" appearance, shown by mouse studies to be goblet cells. The other morphology had no nucleus and was observed by rigid confocal probe microscopy and scanning electron microscopy in the villi of Math1(DeltaIntestine) mice, which lack goblet cells. In the mouse, tumor necrosis factor alpha (0.33 microg/g intraperitoneally) increases cell shedding by 27-fold and caused loss of barrier function across 20% of resultant gaps. CONCLUSIONS: Confocal endomicroscopy can distinguish between epithelial discontinuities (gaps) and goblet cells in human intestine. Results suggest that the sealing of epithelial gaps must be considered as a component of the intestinal barrier and has potential implications for intestinal barrier dysfunction in human disease.
    Citation
    Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. 2007, 133 (6):1769-78 Gastroenterology
    Journal
    Gastroenterology
    URI
    http://hdl.handle.net/10541/71914
    DOI
    10.1053/j.gastro.2007.09.011
    PubMed ID
    18054549
    Type
    Article
    Language
    en
    ISSN
    1528-0012
    ae974a485f413a2113503eed53cd6c53
    10.1053/j.gastro.2007.09.011
    Scopus Count
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    All Paterson Institute for Cancer Research

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