Leukocyte phenotype and function predicts infection risk in renal transplant recipients.
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Cohort Studies↗
Biomedical subjects
R C Atkins
Publications and source records attributed to R C Atkins.
Glomerulonephritis.
The term glomerulonephritis encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus and other compartments of the kidney. Studies with animal models have shown the crucial interaction between bone-marrow-derived inflammatory cells and cells intrinsic to the kidney that is both fundamental and unique to the pathogenesis of glomerulonephritis. The mechanisms of interaction between these cells and the mediators of their coordinated response to inflammation are being elucidated. Despite these pathophysiological advances, treatments for glomerulonephritis remain non-specific, hazardous, and only partly successful. Glomerulonephritis therefore remains a common cause of end-stage kidney failure worldwide. Molecule-specific approaches offer hope for more effective and safer treatments in the future.
Glomerulonephritis↗
Transplantation of kidneys from living related donors. Comparison with cadaveric kidney transplantation.
In a series of 271 transplantations of renal allografts, performed over 10 years, the rates of graft survival, patient survival, and morbidity in the recipients of allografts from living related donors (47 allografts) have been compared with those in the recipients of cadaveric allografts (224 allografts). The one-year graft survival rates were 88% for allografts from living related donors (100%, if these were HLA-identical) and 55% for cadaveric allografts, while the patient survival rates were 97% and 87%, respectively, in the same period. Morbidity rates (expressed as the number of days spent in hospital) for recipients of allografts from living related donors were approximately 50% of those for recipients of cadaveric grafts. Complications in the living related donors were minimal, and acceptable. It is concluded that transplantation of allografts from living related donors has many advantages over transplantation of cadaveric kidneys, and is a valuable adjunct to a cadaveric renal transplantation programme. Greater use of living related kidney donors should be encouraged in Australia.
Adolescent↗
Secretion of bioactive interleukin 1 by rat testicular macrophages in vitro.
The relative capacities for testicular macrophages and resident peritoneal macrophages to secrete the pro-inflammatory cytokine, interleukin 1 (LL-1), in response to stimulation by bacterial lipopolysaccharide (LPS), were compared in vitro. Macrophages were isolated from adult male rat testicular interstitial cells or peritoneal lavage by adherence to glass coverslips or plastic culture dishes. The macrophages were immediately cultured, with or without a maximal dose of LPS (1 mu g/ml), over 24 hours at 32 degrees Celsius. Bioactive LL-1 production was measured by a sensitive thymocyte proliferation bioassay, employing recombinant human LL-1 beta as the reference standard. In comparison with the peritoneal macrophages, testicular macrophages displayed only a very small response to LPS, producing 2.8% of the amount of LL-1 per cell secreted by peritoneal macrophages cultured under identical conditions. Production of authentic LL-1 was confirmed by inhibition of the bioassay response in the presence of human recombinant LL-1 receptor antagonist. A small molecular mass (<10 kDa based on ultrafiltration) inhibitor of LL-1 bioactivity was also present in the medium collected from both cultures, but this inhibitory activity did not account for the differences in activity observed. In cultures of total peritoneal cells under similar conditions, addition of testosterone (10-1,000 ng/ml) did not affect LL-1 production in response to LPS. These data indicate that testicular macrophages have a reduced ability to secrete bioactive IL-1, and they provide further evidence for an altered capacity for immune responses within the testis.
Animals↗
A functional role for osteopontin in experimental crescentic glomerulonephritis in the rat.
This study examined whether osteopontin (OPN), a molecule with monocyte chemotactic and adhesive activity, participates in macrophage-mediated renal disease, Accelerated anti-glomerular basement membrane glomerulonephritis was induced in groups of six rats. Animals were treated with a neutralizing anti-OPN or an irrelevant control antibody over days 0-7 (induction phase) or days 7-14 (established disease). Administration of the control antibody had no effect on the severity of the disease. In contrast, anti-OPN treatment significantly reduced glomerular injury (urinary protein excretion) and prevented a loss of renal function (creatinine clearance) during the induction of disease. This was accompanied by a significant reduction in renal macrophage and T-cell accumulation, T-cell activation, and histological injury (glomerular hypercellularity, segmental lesions, crescents, and tubulointerstitial lesions). An important finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reduction in glomerular injury and recovery of renal function in association with inhibition of macrophage and T-cell accumulation, T-cell activation, and histological damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in the kidney. Interestingly, anti-OPN treatment significantly reduced skin swelling and leukocyte infiltration in the delayed type hypersensitivity response. However, anti-OPN treatment had no effect on the humoral immune response. In summary, this study has demonstrated that OPN plays a functional role in macrophage and T-cell accumulation and renal damage in both the induction and progression of a rat model of crescentic glomerulonephritis. Thus, OPN may be of pathological importance in human glomerulonephritis and in cell-mediated immune diseases generally.
Animals↗