[Freeze etching preparation of tissue fragments with the EPA 100 demonstrated on the nose septum of the mouse].
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Biomedical subjects
Publications and source records attributed to D Kerjaschki.
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Heymann nephritis is a glomerulonephritis induced in rat by injecting kidney extracts. The responsible antigen is known to consist of two high molecular weight glycoproteins, gp330 and gp300, located in renal tubular brush border cells. We show that rabbit antibodies made against purified rat gp330 react in immunofluorescence tests with several polarized epithelia present in pre- and post-implantation mouse embryos, as well as with murine trophoblastoma cells. Immunoprecipitation experiments demonstrate that anti-gp330 antibodies also recognize two components with relative molecular weights of 330 and 300 Kd in mouse embryonic cells. Furthermore, sequential immunoprecipitation experiments and limited proteolysis tests suggest that these two components are identical with brushin, a glycoprotein set known to be present in a mouse early embryonic epithelium and in adult kidney cells. Finally, ultrastructural studies demonstrate that anti-gp330 antibodies react with molecules preferentially located in coated pits of murine early epithelial cells. These results show that Heymann nephritis antigen has an embryonic counterpart closely related to, if not identical with, previously identified brushin glycoproteins. These molecules could be a receptor to an unknown ligand or a structural component of coated pit membrane.
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Membranous glomerulopathy (MGN) is a frequent cause for nephrotic syndrome in adults. In this overview, the basic pathogenic features of Heymann nephritis, a "classical" model of MGN in rats, are compared with those of human MGN. While the pathogenic antigen(s) of rat Heymann nephritis (the polyspecific receptor protein gp330/megalin), and that of human MGN (unknown) are obvioulsy different, the results indicate that the molecular mechanisms of proteinuria may be similar in both instances and involve the formation of lipid peroxidation adducts in the glomerular capillary filter. As a consequence, probucol - an efficient inhibitor of lipid peroxidation - drastically reduces proteinuria both in Heymann nephritis and in a large proportion of human patients with MGN.
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