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R J Glassock

Publications and source records attributed to R J Glassock.

At least 127 records · Page 7Linked to original sources
PubMed1968

Autologous immune complex nephritis induced with renal tubular antigen. I. Identification and isolation of the pathogenetic antigen.

The nephritogenic antigen, responsible for the immunogenic stimulus in experimental allergic glomerulonephritis induced with tubular antigen, has been identified as a renal tubular epithelial (RTE)-specific antigen and has been isolated in a relatively purified form. This antigen, RTE-alpha(5), is a distinct and antigenically specific lipoprotein of high density which is derived primarily from the brush border of proximal convoluted tubular epthelium of the rat kidney. It has been suggested that this molecule may be a plasma membrane subunit. Immunization of rats with as little as 3 microg N of RTE-alpha(5) in complete Freund's adjuvant has effectively induced this form of membranous glomerulonephritis. RTE-alpha(5) is not a constituent of normal rat glomeruli; however, with the onset of autologous immune complex nephritis it is deposited in a granular fashion along glomerular capillary walls indistinguishable from the deposits of gamma-globulin and complement. The antigenic specificity of this antigen and its tissue derivation has been explored, and the observations support the autologous immune complex pathogenesis of the glomerulonephritis induced in rats by immunization with renal tubular antigen.

Animals↗
PubMed1968

Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism.

The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 microg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with gamma-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated.

Adjuvants, Immunologic↗
PubMed1967

The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis.

These observations established the presence of anti-GBM antibodies in the sera and/or kidneys of six humans with glomerulonephritis. Further, it seems clear that these antibodies do combine with the host's glomeruli in vivo and with GBM antigen of several species in vitro. Transfer of acute glomerulonephritis to normal recipient monkeys was possible with serum or renal eluate IGG from the three patients with anti-GBM antibodies in whom sufficient material was available. Based on this transfer of nephritis and on the presence of these antibodies at the site of injury in the nephritic kidneys of both the patients and the recipient monkeys, it seems likely that they are at least a contributing, if not primary, cause of the glomerular injury. The frequency of anti-GBM antibodies in human nephritis is not certain, but on the basis of preliminary observations it would appear that they are present in all cases of Goodpasture's nephritis and somewhat less than half of the cases of subacute and chronic glomerulonephritis of adults. The nature and source of immunogen stimulating the production of anti-GBM antibodies is not known, but the presence of potentially nephritogenic GBM antigens in normal urine raises the question of possible autoimmunization. From a practical point of view, it appears that patients forming anti-GBM antibodies may not be good candidates for renal transplantation since they are likely to produce in the transplants the nephritic changes already suffered by their own kidneys.

Animals↗
PubMed1967

Autologous immune-complex pathogenesis of experimental allergic glomerulonephritis.

A renal tubular epithelial antigen is deposited in association with gamma globulin and complement in glomeruli from rats with experimental allergic glomerulonephritis induced by immunization with renal tubular antigens. Apparently, in normal kidneys this antigen is concentrated in the distal segment of the proximal convoluted tubular epithelium, and the principal source of this antigen in the glomerular deposits is autologous. This form of glomerulonephritis provides an experimental prototype for what may be termed "autologous immunecomplex" diseases.

Animals↗
PubMedDate not supplied

Glomerular therapeutics: looking back, looking forward.

Fifty years ago, the prospects for treatment of glomerulonephritis were dim. Beginning around 1950 the field of "glomerular therapeutics" was begun by the introduction of new agents (adrenocorticotrophic hormone, cortisone, nitrogen mustard) as possible disease-modifying therapies for the various forms of glomerular disease. For the next several decades these and other agents (azathioprine, cyclophosphamide, chlorambucil, prednisone) were used therapeutically in a largely uncontrolled and anecdotal fashion. The application of randomized, controlled trials led to the adoption of some forms of therapy as both effective and reasonably safe, and the rejection of others as either ineffective or hazardous. New regimens involving different routes of administration or dosing schedules were adopted. After about another two decades, new and increasingly selective agents began to be introduced into the therapeutic armamentarium (cyclosporine, mycophenolate mofetil). Diseases previously associated with a very poor outcome were transformed into manageable disorders. The consequences of glomerular disease (e.g., nephrotic syndrome, chronic renal failure) were now subject to control and alleviation in many circumstances. The next transformation of "glomerular therapeutics" is now under way. The revolution in molecular genetics and pharmacogenomics will allow new agents to be developed that target specific aspects of the pathogenic mechanisms underlying glomerular disease. This transformation will not be an easy one, because development, testing, approval, and application of these new concepts in therapeutics (e.g., somatic gene therapy) will be time consuming and expensive. Eventually, the understanding of the genetic basis of susceptibility to glomerular disease and its progression will allow a preventative and curative, rather than palliative, strategy to emerge.

Disease Progression↗