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This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.

Hydrogen peroxide (H2O2) and other oxygen metabolites have been implicated in the pathogenesis of cell and tissue injury. The nature of the injury occurring in cells exposed to oxygen metabolites is unknown. A549 cells, derived from human lung carcinoma, were exposed to glucose-glucose oxidase or hydrogen peroxide in vitro. The distribution of actin and cytokeratin filaments, as well as 51chromium (51Cr) release and trypan blue dye exclusion were assessed. Both glucose-glucose oxidase and H2O2 resulted in changes which were time- and dose-dependent. Alterations in the cytoskeleton were detected by immunofluorescence microscopy at two hours, at which time the cells excluded trypan blue dye, while 51Cr release and trypan blue uptake first occurred at 8 h and required a five-fold greater concentration of glucose oxidase. The addition of catalase to glucose-glucose oxidase or H2O2, or inactivation of glucose oxidase by boiling, abrogated the injury. Therefore, one of the early targets of H2O2-induced cell injury may be the cytoskeleton.

The results of the evaluation of the basic science curriculum in a regionalized medical education program in the states of Washington, Alaska, Montana, and Idaho (WAMI) are presented and discussed. The hypothesis that students taking the first quarter of basic science at universities remote from the Unversity of Washington School of Medicine (UWSM) will be no different in academic performance from those who remain at the UWSM is tested. The variables considered were student performance on (a) common tests in Anatomy/Histology, Biochemistry, Mechanisms of Physiology, and Epidemiology; (b) subsequent course work at the UWSM; and (c) the mini-tests and Part I of the examinations of the National Board of Medical Examiners. The developement of the common tests is described. Analysis of variance indicates that the null hypothesis cannot be rejected at the .05 level.

To study the interaction of positively charged antibodies in immune complexes with the fixed negative charge on the glomerular capillary wall, chemical cationization of antibody was accomplished with the maintenance of antigen-binding activity. These cationized antibodies bound rapidly to glomeruli but did not persist. Large-latticed immune complexes formed with these cationic antibodies showed rapid deposition and persistence in renal glomeruli, even when administered in small doses. Electron-dense deposits were present at the anionic sites in the glomerular basement membrane at 1 min and 1 h, with extensive subendothelial deposits present from 12 to 72 h. By 14 d, the deposits were seen in the subepithelial region and the glomerular mesangium. The administration of small-latticed immune complexes prepared with cationized antibody revealed initial deposition without persistence in glomeruli in a manner similar to cationized antibodies alone. Thus, the positive charges on antibodies in immune complexes contribute to the deposition and persistence of the complexes in glomeruli, particularly in the subendothelial area.

Glomerular lesions have been recognized in nearly all forms of malignant diseases. The incidence within each category of malignancy varies substantially but in most series represents less than 2% of the population. While there is a considerable variety of glomerular lesions, a number of general statements may be made. In Hodgkin's disease and other lymphomas, the most common lesion is minimal lesion nephrotic syndrome, reflecting possibly an anomaly of T cell function. Amyloidosis which used to be the commonest lesion has nearly disappeared. On the other hand, in patients with chronic lymphocytic leukemia a large proportion of glomerular lesions fall into the category of proliferative glomerulonephritis. In carcinoma the vast majority of glomerular lesions with proteinuria or the nephrotic syndrome are due to membranous glomerulonephritis. This suggests either a local alteration of fixed glomerular antigens, or localization of tumor antigens planted in the glomeruli leading to the formation of local immunocomplexes. Amyloid AA is still frequent in carcinoma and complicates as much as 3% of renal adenocarcinomas.

20 patients with active SLE without clinical evidence of renal involvement underwent percutaneous renal biopsy. 12 had varying proliferative changes on light microscopy. Of 19 ultrastructural examinations performed only 3 had no electron-dense deposits. Serum C3 and C4 levels were 63 +/- 8 and 8 +/- 2 mg% in patients with subendothelial deposits, compared to 142 +/- 27 and 27 +/- 6 mg%, respectively, in patients without deposits (p less than 0.01). All patients with diffuse proliferative changes had subendothelial deposits; however, one with normal light microscopy and another with focal proliferation also had them. It is concluded that no variant of lupus nephropathy can be excluded on clinical grounds alone.