89,954 research outputs found

    The time-dependent rearrangement of the epithelial basement membrane in human skin wounds

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    In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane

    Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice

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    The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane–binding anti-DNA antibody. Basement membrane–binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis

    Identification of a target antigen in human anti-tubular basement membrane nephritis

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    Identification of a target antigen in human anti-tubular basement membrane nephritis. Sera from two patients with primary anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, one a renal allograft recipient and the other with spontaneous anti-tubular–basement–membrane disease, were analyzed for the specificity of their autoantibodies. Both sera had circulating antibodies that reacted by ELISA with extracts of tubular basement membrane from several species, but failed to react significantly with extracts of glomerular basement membrane. Reactive antigen was solubilized with 6 M guanidine-HCl, 6 M urea, with reduction and alkylation, and with sodium dodecylsulfate. Digestion of the basement membrane with collagenase released relatively small quantities of antigen from the membrane, and trypsin and pepsin destroyed its antigenicity. The antigenic activity was characterized with respect to its size distribution by gel filtration and by immuno-overlay analysis of protein blots. Collectively, the results indicate that the major reactivity of both sera is directed towards a Mr 58,000 component that is unique to the tubular basement membrane. Minor reactivities toward high molecular weight components common to both glomerular and tubular basement membranes were detected by immuno-overlay analysis. This study identifies an antigen that is involved in human anti-tubular–basement–membrane–mediated tubulointerstitial nephritis, and demonstrates an advantage of the use of denaturing extraction over proteolytic methods to prepare the antigen

    Basement Membrane Polarizes Epithelial Cells and Its Loss Can Result in Neoplastic Disorganization

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    The studies described in this dissertation demonstrate that basement membrane may be required for maintenance of organized epithelial tissue architecture. The structural organization of normal rat pancreatic acinar epithelium is fully characterized in order to analyze its neoplastic disorganization within a pancreatic acinar cell tumor. Transmission electron microscopy and indirect immunofluorescence microscopy of frozen semithin tissue sections are utilized to localize different components of the plasmalemma, cytoskeleton, basement membrane and connective tissue. Normal acinar cells sit on a continuous basement membrane and display a polarized distribution of intracellular organelles, cytoskeletal elements, and distinct membrane domains while these organized cell relations are lost within the parenchyma of the pancreatic acinar carcinoma. This tumor-associated disorganization of normal epithelial cell relations correlates directly with absence of integral basement membrane within the parenchyma of this tumor. Interestingly, pancreatic acinar tumor cells also retain the ability to reorient in vivo when in direct contact with intact basement membrane appears only along the connective tissue boundary.Amniotic basement membrane and stroma are also utilized for studies designed to determine if basement membrane is sufficient to trigger pancreatic epithelial tumor cell polarization in vitro.Thus, basement membrane is necessary and sufficient for reorientation of independent epithelial tumor cells in vitro and so the organization of a polarized epithelium may be directed by forces from outside the cell via basement membrane. Stability of epithelial form may require continued presence of intact basement membrane and its dissolution could be responsible for neoplastic disorganization of epithelial architectural relations as observed within the pancreatic acinar cell carcinoma. A model for architectural regulation of tissue structures with basement membrane as a transducer of physical forces is presented. (Abstract shortened with permission of author.

    The Development of Basement Membranes Associated With Vascular Invasion of the Brain in the Chick Embryo

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    Since a basement membrane is present on all blood vessels and also on all tissues of ectodermal origin, the blood vessels of the central nervous system should have two basement membranes, one related to the blood vessel, the other related to the nervous tissue. Also, the tissue space usually bordering on the basement membranes should in the central nervous system separate the two. In the adult brain and spinal cord, however, only one basement membrane and no tissue space surround the blood vessels of the central nervous system. This study, therefore, has been concerned with the embryonic development of blood vessels of the central nervous system and the manner in which the single basement membrane - no tissue space relationship of blood vessels and nervous tissues is produced. Twenty-seven chick embryos (48 hours to 5 days incubation) were serial sectioned at 2-4p and stained by the periodic acid-Schiff (PAS) technique. PAS positive basement membranes were demonstrated for light microscopy with this technique. Blood vessels are formed in the mesenchyme surrounding the central nervous system. The early blood vessels lack a basement membrane. When the vessels invade the tissues of the central nervous system, the basement membrane of the central nervous system invaginates to form a membrane for the vessel and becomes applied directly to the surface of the vessel. The invaginated central nervous basement membrane remains continuous with the basement membrane on the surface of the central nervous system. Present techniques cannot Indicate whether additions to the invaginated basement membrane are made by the endothelial cells of the vessels

    Correlated alterations in prostate basal cell layer and basement membrane

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    Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion
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