Membranous glomerulonephritis in the mouse

Membranous glomerulonephritis in the mouse. Glomerulonephritis was induced in C57.B110 mice by a single injection of rabbit IgG against homologous, pronase-digested, renal tubular antigens. The heterologous phase was characterized by a transient increase of glomerular permeability with fixation of rabbit IgG to the capillary walls, in a linear or fine-granular pattern, and to the brush borders of the proximal tubuli. The autologous phase was marked by the immune response to the injected protein, during which subepithelial immune deposits, consisting of mouse IgG1, rabbit IgG, and mouse C3 developed. Small amounts were still present at 1 year after the injection of antiserum. The antibody response of the mice correlated with the development and resolution of the deposits. None of the mice developed a nephrotic syndrome. Control mice treated with normal rabbit IgG did not show immune deposits in their kidneys at any stage despite a comparable antibody response to rabbit IgG. Immunoelectronmicroscopy showed that the rabbit antibodies fixed directly to an antigen in the cell membrane of the glomerular visceral epithelium. It seems, therefore, likely that in situ formation of subepithelial immune complexes occurred in the autologous phase by fixation of mouse immunoglobulins to rabbit IgG already present in the glomerular wall.Glomérulonéphrite extra-membraneuse chez la souris. Une glomérulonéphrite a été induite chez des souris C57.B110 par une injection unique d'IgG de lapin contre des antigènes tubulaires rénaux homologues, digérés par de la pronase. La phase hétérologue était caractérisée par une augmentation transitoire de la perméabilité glomérulaire avec fixation d'IgG de lapin aux parois capillaires, d'une façon linéaire ou finement granuleuse, et aux bordures en brosse des tubules proximaux. La phase autologue était marquée par la réponse immune à la protéine injectée, pendant laquelle des dépôts immuns sous-épithéliaux, consistant en de l'IgG1 de souris, de l'IgG de lapin et du C3 de souris, se sont développés. Il en restait encore de faibles quantités 1 an après l'injection de l'antisérum. La réponse anticorps des souris était corrélée avec le développement et la disparition des dépôts. Aucune des souris n'a développé de syndrome néphrotique. Les souris contrôles traitées avec de l'IgG de lapin normal n'ont pas eu de dépôts immuns dans le rein à aucun stade, malgré une réponse anticorps aux IgG de lapin comparable. La microscopie immuno-électronique a montré que les anticorps de lapin se fixaient directement à un antigène situé sur la membrane des cellules de l'épithélium viscéral glomérulaire. Il semble donc probable que la formation in situ de complexes immuns sous-épithéliaux est survenue à la phase autologue par fixation d'immunoglobulines de souris à de l'IgG de lapin déjà présente dans la paroi glomérulaire

Expression of cyclooxygenase-2 and epidermal growth factor receptor in primary and recurrent glioblastoma multiforme

PURPOSE: To investigate the pattern and level of cyclooxygenase-2 (COX-2) expression in a series of high grade primary and recurrent glioblastoma multiforme (GBM) and correlation with time to recurrence and patients' survival following therapy. The relationship between COX-2 and epidermal growth factor receptor (EGFR) immunoreactivities was evaluated. MATERIALS AND METHODS: Specimens of 14 primary and 14 recurrent GBMs (eight pairs) following surgery and full course radiation therapy were processed for immunostaining on COX-2 and EGFR. Tumor cell positivity was semi-quantitatively scored. COX-2 scores of the primary tumor and recurrence were correlated with the time to radiological tumor progression and patients' survival. RESULTS: COX-2 positive tumor cells were disseminated throughout the tumor parenchyma. The intensity and pattern of COX-2 expression were heterogeneous, with predominant expression in areas surrounding tumor necrosis. Scoring of COX-2 positivity revealed values between 1 and 80% of the cells. Primary GBMs with COX-2 expression levels between 25% and 70% of the tumor cells showed a shorter time to radiological recurrence than GBMs with <10% COX-2 positive tumor cells (respectively, 219 +/- 50 and 382 +/- 77 days). No correlation was found between the COX-2 expression in the primary tumor and patients' survival (r (s) = -0.073) following therapy. No correlation was found either between COX-2 and EGFR immunoreactivity. CONCLUSIONS: Immunohistochemical expression of COX-2 in GBM showed large variation. Hence, determination of COX-2 expression in tumor specimen for each individual might be relevant for selection of those patients, who could benefit from adjuvant therapy with selective COX-2 inhibitors