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Biomedical subjects

G R Gallo

Publications and source records attributed to G R Gallo.

At least 37 records · Page 2Linked to original sources

Interaction of immune complexes with glomerular heparan sulfate-proteoglycans.

The binding characteristics of cationic and more neutral immune complexes with heparan sulfate-proteoglycan enriched anionic sites of glomerular basement membrane and mesangial matrix were studied. Rat kidneys were treated either with buffers alone or buffers containing heparitinase or chondroitinase-ABC followed by perfusion with cationic or native immune complexes. Tissues were processed for immunofluorescence and transmission electron microscopy after fixation with glutaraldehyde or tannic acid glutaraldehyde. Kidneys perfused with radioiodinated immune complexes were processed for light and electron microscopic autoradiography. In addition, glomeruli from kidneys perfused with radioiodinated immune complexes were isolated and counted for radioactivity. By immunofluorescence the cationic immune complexes deposited linearly along the glomerular basement membrane. By electron microscopy, the cationic complexes localized mainly in the inner and outer layers of the glomerular basement membrane and to a certain extent in the mesangial matrix in a distribution that corresponded to previously documented anionic sites. Whereas heparitinase treatment abrogated the binding of cationic immune complexes in both glomerular basement membrane and mesangial matrix, chondroitinase-ABC treatment did not cause any decrease in binding. In contrast, more neutral immune complexes appeared to be nonspecifically trapped in the mesangium, and their distribution was unaffected by both enzymatic treatments. Light and electron microscopic autoradiography and counts of isolated glomeruli confirmed these findings. The results overall indicate that cationic immune complexes bind electrostatically to the heparan sulfate-proteoglycan enriched anionic sites of the glomerular basement membrane and mesangial matrix, while more neutral immune complexes are nonspecifically trapped in the mesangium of the renal glomerulus.

Animals↗

Use of information sources at a university hospital drug information service.

The frequency of use of various sources to answer drug information requests in a university hospital drug information service was studied. All of the drug information requests received by the University of Minnesota Drug Information Service (UMDIS) between November 1, 1983, and January 27, 1984, were included in the evaluation. A total of 1448 requests from health-care professionals and consumers were reviewed. The 10 most frequently used information sources in order of most to least often used were Facts and Comparisons, previous knowledge or experience of the UMDIS staff, Drugdex, Martindale: The Extra Pharmacopoeia, USP DI, the UMDIS files, information from pharmaceutical manufacturers, Goodman and Gilman's the Pharmacological Basis of Therapeutics, and Meyler's Side Effects of Drugs. Forty percent of the requests were from consumers. Pharmacists should characterize the type and number of drug information requests they receive and should consider the accessibility of a drug information service and biomedical library when deciding which references to purchase.

Catalogs, Drug as Topic↗

An international survey of drug information centers.

A questionnaire was developed to characterize the location, operation, personnel, reference resources, and functions of drug information centers in countries throughout the world other than the United States. The questionnaire was mailed to 100 drug information centers or pharmacy practitioners (primarily faculty) in 65 countries. The majority of drug information centers responding to this questionnaire were located at and funded by university based hospitals. Most were open eight hours per day and engaged in the following activities: answering requests for information, publishing pharmacy bulletins, teaching, continuing education, and providing information directly to pharmacy and therapeutics committees. Additional information gathered from this survey included: common references and journals maintained by drug information centers, user demographics, and a request profile. Although many similarities among the information centers were found, interesting observations regarding their differences may be made. It is important that drug information centers share their experiences so that others may learn about their new and innovative programs.

Drug Information Services↗

Charge-related deposition of immune complexes in the glomerular basement membrane is independent of Fc effector function.

Differently charged immune complexes composed of fragments of bovine gamma globulin (BGG) antigen and fragments of rabbit anti-BGG antibody lacking FC portions were used for a study of the role of charge in deposition and localization within the mouse glomerulus. Preformed soluble complexes were made from native heterogeneous, cationic, or anionic F(ab')2 fragments of BGG and of rabbit antibody to BGG, and were injected intravenously. The distribution in the kidney was studied by immunofluorescence and electron microscopy. Cationic but not anionic or heterogeneous complexes diffusely localized in the glomerular basement membrane in both subepithelial and subendothelial sites. In contrast, more neutral or anionic complexes localized less prominently and were limited to the mesangium. The findings suggest that electrostatic interactions independent of Fc effector functions of immunoglobulins can be responsible for glomerular immune complex localization.

Animals↗

IgA nephropathy: perspectives on pathogenesis and classification.

IgA nephropathy has received growing attention since its recognition 18 years ago. In this review the salient demographic, clinical and pathologic features are summarized. Next follows a discussion of the pathogenesis of the disease in light of current clinical and experimental data, with a proposal for classification based upon immune response, disordered immunoregulation, and the impairment of clearance of immune complexes.

Adolescent↗

Glomerulonephritis in bacterial endocarditis.

For a modern assessment of the clinical and morphologic features of glomerulonephritis accompanying bacterial endocarditis, postmortem and renal biopsy files were reviewed for the years 1965 to 1979, a period of changing epidemiology, etiology, and therapeutic regimens in infective endocarditis. The incidence of glomerulonephritis in 107 patients examined at postmortem was 22.4%; focal glomerulonephritis was present in 8.4%, diffuse glomerulonephritis in 14%. Glomerulonephritis occurred as frequently in acute as in subacute bacterial endocarditis. Staphylococcus aureus, which has replaced Streptococcus viridans as the predominant etiology of fatal bacterial endocarditis, was frequently associated with glomerulonephritis, especially in parenteral drug abusers. Renal functional impairment due to focal glomerulonephritis did not necessitate dialysis or contribute to the death of any patient. Presentation with advanced renal insufficiency due to diffuse glomerulonephritis was associated with both failure of antibiotic therapy to eradicate infection and failure to recover renal function. In patients with diffuse glomerulonephritis and less severe impairment of renal function, antibiotic therapy was successful in achieving bacteriologic cure, and complete recovery of renal function occurred in the majority. Features of persistent glomerular disease were frequent in patients with diffuse glomerulonephritis long after bacteriologic cure of endocarditis.

Adolescent↗

Drug information services: how health care professionals use the information provided.

This study has shown that the Drug Information Service is providing useful information to health professionals and that the information is being applied to patient-specific problems. More research, however, is needed to more concretely document patient outcomes in terms of the length of hospitalization, the number of laboratory tests ordered and the total number and expense of the drugs received.

Consumer Behavior↗

Nondissociating cationic immune complexes can deposit in glomerular basement membrane.

The mechanisms by which immune complexes deposit in the glomerular basement membrane have been the subject of much debate, with the relative importance of direct deposition of circulating immune complexes (IC) vs. formation of IC in situ from the binding of circulating antibody to structural or exogenous planted antigen being at issue. In order to determine whether intact IC can deposit as such, covalently linked IC were prepared by a two-step reaction involving the bifunctional reagent toluene-2,4-diisocyanate (TDI), the antigen bovine gamma globulin (BGG), and rabbit anti-BGG antibody. Antigen and antibody were covalently cross-linked, with little self-linkage of antigen or antibody, and IC were purified by gel filtration. The net charge of the complexes was varied by chemical means, either before or after IC formation. When cationic IC were injected intravenously into mice, there was codeposition of antigen and antibody diffusely in the glomerular basement membrane (GBM), and deposits were observed ultrastructurally in the laminae rarae, interna and externa, and the lamina densa. Thus, under conditions of restricted appropriate charge, intact IC can cross the glomerular basement membrane and deposit in subepithelial sites without being excluded by size alone.

Animals↗

Experimental IgA nephropathy induced by oral immunization.

To test the hypothesis that IgA nephropathy can result from a mucosal immune response, mice were orally immunized with one of three protein antigens for 14 wk. Such mice exhibited an essentially pure mucosal antibody response characterized by specific IgA-producing plasma cells in exocrine sites and specific IgA antibodies in serum. Furthermore, 73% of immunized mice had IgA and 88% had immunogen deposited in the glomerular mesangium, and 64% of immunized mice examined ultrastructurally had electron-dense mesangial deposits. All three were present concurrently in 57% of the immunized mice. No differences in regard to IgG or IgM were observed between immunized and control mice for any of these parameters. Mucosal immunization therefore can result in a specific immune response that leads to mesangial deposition of immune complexes containing IgA antibody. In its fundamental features the experimental renal lesion resembles that seen in the human disease IgA nephropathy.

Administration, Oral↗

Monoclonal antibodies to human complement receptor (CR1) detect defects in glomerular diseases.

The complement receptor for C3b of the epithelial cells of human glomeruli is structurally and functionally very similar or identical to CR1, the complement receptor for C3b and C4b present on the membrane of red cells and leukocytes. Four monoclonal antibodies directed against separate epitopes of CR1 react with an antigen in the glomeruli, which appears to be present on the epithelial podocytes. Moreover, the monoclonal antibodies very effectively inhibit the binding of C3b-bearing red cells to the glomeruli. The pattern of immunofluorescence of the receptor was normal or slightly altered in patients with minimal change disease, mesangial proliferative glomerulonephritis (GN), or idiopathic membranous GN. Glomeruli with endocapillary proliferation showed some attenuation of staining. Glomeruli in which the capillary tuft architecture was altered, or of patients with systemic lupus erythematosus, or of patients with diffuse diabetic nephropathy tended to have few foci or no staining for the receptor. No correlation was found between the intensities of staining of the C3b receptor and of C3 antigen deposited in the glomeruli.

Amyloidosis↗