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  • 1
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 116 (1990), S. 177-184 
    ISSN: 1432-1424
    Keywords: tight junction ; tight junction regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary All epithelia slough dying cells but the consequences of this physiological process to epithelial barrier functions is unknown. In mammalian small intestine absorptive cells are known to migrate from the villus base to the villus tip from which they slough. These villus tip extrusion zones are often envisioned as sites at which macromolecules could leak across the epithelium. However, only trace amounts of macromolecules cross this epithelium even though, based on known epithelial turnover rates, extrusion events occur millions of times daily. Here, we examine the characteristics of the epithelial barrier to macromolecular permeation at villus tip extrusion zones in rats and hamsters. Freeze-fracture, light and electron microscope studies reveal that extruding cells do not leave transient holes behind as they lift from the epithelium. Rather, as cells extrude, processes of adjacent cells extend under them. Moreover, tight junction elements proliferate between extruding cells and their neighbors and appear to move down the lateral margin of the extruding cell as it extends into the lumen. These observations suggest that newly formed junctional elements “zipper” the epithelium closed as extrusion proceeds thus preventing epithelial discontinuities from occurring. Correlative in vivo perfusion experiments using horseradish peroxidase as a macromolecular-tracershow that the above described dynamic alterations in tight junctions at extrusion sites are generally sufficient to prevent transepithelial leaks of macromolecules.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1424
    Keywords: intestine ; tight junction ; paracellular pathway ; transepithelial resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Current models of intestinal transport suggest cells which absorb ions are located on the villus while secretory cells are located in the crypt and putatively have paracellular pathways which are highly conductive to Na+. One approach to assess possible variation in small intestinal paracellular conductance along the crypt-villus axis is to morphometrically analyze the structural aspects of crypt and villus tight junctions (TJs) which relate to paracellular resistance. Such detailed analysis of junctional structure in this heterogeneous epithelium would permit one to compare intestinal TJ structure-function relationships with those in a structurally simpler epithelium such as that of toad urinary bladder. This comparison would also be of considerable interest since previous similar comparisons have failed to consider in detail the geometric dissimilarity between these two epithelia. We applied light, electron microscopic, and freezefracture morphometric techniques to guinea pig ileal mucosa to quantitatively assess, for both crypts and villi, linear TJ density, relative surface contributions, and TJ strand counts. Mean linear TJ densities were 76.8 m/cm2 for crypt cells and 21.8 m/cm2 for villus absorptive cells. Mean TJ strand counts were 4.45 for undifferentiated crypt cell TJs and 6.03 for villus absorptive cell TJs. The villus constituted 87% and the crypt 13% of total surface. We utilized these data to predict paracellular conductance of cryptsvs. villi based on equations derived from those of Claude (P. Claude,J. Membrane Biol. 39:219–232, 1978). Such analysis predicts that 73% of ileal paracellular conductance is attributable to the crypt. Furthermore, we obtained literature values for paracellular resistance in mammalian ileum and toad urinary bladder and for toad bladder TJ structure and linear density and constructed a relationship which would allow us to more accurately compare TJ structure-function correlates between these two epithelia. Such a comparison, which considers both surface amplification and TJ structure and distribution in these epithelia, shows that one would predictin vitro measured values for paracellular resistance should be approximately two orders of magnitude less in mammalian ileum than in toad urinary bladder. This predicted discrepancy (115-fold) correlates well with the observed difference (100-fold). These findings suggest that highly similar TJ structure-function relationships apply to these geometrically dissimilar tissues and that, in mammalian ileum, the crypt compartment may be responsible for the majority of net ileal paracellular conductance. We speculate that high crypt linear TJ density and low crypt TJ strand counts may serve as the structural basis of massive paracellular Na+ movement which is coupled to active Cl− secretion and appears to originate from the crypt following exposure to intestinal secretagogues.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 66 (1982), S. 145-157 
    ISSN: 1432-1424
    Keywords: tight junction ; intestine ; goblet cell ; epithelial permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Two major cell types, goblet and absorptive cells, dominate the epithelial lining of small intestinal villi. We used freezefracture replicas of rat ileal mucosa to examine the possibility that tight junction structure, known to relate to transepithelial resistance, might vary with cell type. Tight junctions between absorptive cells were uniform in structure while those associated with villus goblet cells displayed structural variability. In 23% of villus goblet cell tight junctions the strand count was less than 4 and in 30% the depth was less than 200 nm. In contrast, only 4% of absorptive cell tight junctions had less than 4 strands and only 9% had depth measurements less than 200 nm. Other structural features commonly associated with villus goblet cell tight junctions but less commonly with absorptive cell tight junctions were: deficient strand cross-linking, free-ending abluminal strands, and highly fragmented strands. Bothin vivo ileal segments and everted loops were exposed to ionic lanthanum. Dense lanthanum precipitates in tight junctions and paracellular spaces were restricted to a subpopulation of villus goblet cells and were not found between villus absorptive cells. After exposure of prefixed ileal loops to lanthanum for 1 hour, faint precipitates of lanthanum were found in 14% of tight junctions and paracellular spaces between absorptive cells compared to 42% of tight junctions and paracellular spaces adjacent to villus goblet cells. When tested in Ussing chambers, the methods used for lanthanum exposure did not lower transepithelial resistance. Everted loops exposed to ionic barium and examined by light microscopy showed dense barium precipitates in the junctional zone and region of the paracellular space of villus goblet cells but not in these regions between absorptive cells. However, the macromolecular tracers, microperoxidase, cytochromec and horseradish peroxidase, were excluded from both villus goblet cell and absorptive cell paracellular spaces inin vivo segments. These findings suggest that a subpopulation of villus goblet cells may serve as focal sites of high ionic permeability and contribute to the relatively low resistance to ionic flow which characterizes the small intestinal epithelium.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 664 (1992), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 60 (1998), S. 143-159 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract The intercellular tight junction is the rate-limiting barrier in the paracellular pathway for permeation by ions and larger solutes. A variety of widely used electrical and flux approaches are used in the analyses of solute permeation through this pathway; however, each has limitations in practice. It is now clear that solute permeation across tight junctions is dynamically regulated by intracellular events with a common effector mechanism apparently tied to the cytoskeleton. These pathways, which regulate tight junction solute permeability, are targets that produce epithelial barrier dysfunction in a variety of disease states. However, regulation of solute permeation across the junctional barrier may also represent a potential means to improve bioavailability of orally administered bioactive solutes.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-0603
    Keywords: tight junction ; neutrophil ; integrin ; epithelium ; inflammation ; transmigration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Typically, electrophysiologic studies of epithelial monolayers are either performed in formalized Ussing chamber systems which yield highly accurate results or in simple setups using recording devices which have limitations in accuracy or the range of measurements which can be performed or both. Here we detail a simple method of interfacing traditionally accurate Ussing chambers systems with commercially available filter supports on which epithelial monolayers can be grown. We also detail simple methods for growing inverted monolayers, suitable for electrophysiologic assays, for use in studies where cells or particles must be layered by gravity on the undersurface (basolateral pole) of the filter. Both approaches allow experiments to be performed on large numbers of monolayers synchronously. As an example of the use of this system, we analyze the sequelae of neutrophil migration across monolayers of the intestinal cell line T84. Neutrophil migration across monolayers can occur in either direction, is dependent on neutrophil surface β2 integrins, and is paralleled by a decrease in epithelial barrier function as detected electrically. We have previously shown in formal Ussing chamber studies that neutrophil-epithelial interactions elicit a modest short-circuit current indicative of electrogenic ion transport. We show here that this short-circuit current response can be readily detected using the simple approach described.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 1994-01-01
    Print ISSN: 0962-8924
    Electronic ISSN: 1879-3088
    Topics: Biology , Medicine
    Published by Cell Press
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  • 9
    Publication Date: 2001-04-01
    Print ISSN: 1529-2908
    Electronic ISSN: 1529-2916
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 10
    Publication Date: 1995-11-01
    Print ISSN: 0006-2960
    Electronic ISSN: 1520-4995
    Topics: Biology , Chemistry and Pharmacology
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