PubMed Health⌕ Search

Biomedical subjects

J S Cameron

Publications and source records attributed to J S Cameron.

At least 19 recordsLinked to original sources
PubMed1992

Tubular and interstitial factors in the progression of glomerulonephritis.

All recent studies of the outcome of different forms of progressive glomerulonephritis concur that a major factor, apparently determining outcome, is the presence and severity of tubulointerstitial changes, and not the degree of glomerular alteration. Moreover, at the time of biopsy, tubulointerstitial changes correlate much better with the glomerular filtration rate. These at first surprising findings are not only useful clinically, but should make us think about our models of how progression takes place in so-called glomerular nephritides. In fact, a major tubulointerstitial infiltrate of immune-competent cells is present in all forms of progressive glomerulonephritis, and again correlates with outcome. In addition, it is now clear the tubular epithelium is capable of synthesising and secreting a number of factors important in fibrogenesis, and of displaying major histocompatibility complex class II antigens and leucocyte-adhesion molecules. Tubular cells could thus present peptides to T helper cells and amplify, or maybe even initiate, immune reactions. Finally, fibrogenesis within the kidney is at last being studied, long after studies have been performed on liver and lung. In the past, too much attention has been paid to reversible inflammation and not enough to irreversible cirrhosis of the kidney.

Glomerulonephritis↗
PubMed1992

Peritoneal drainage: an important element in host defence against staphylococcal peritonitis in patients on CAPD.

The growth of Staphylococcus aureus and coagulase-negative staphylococci were studied in fresh and effluent peritoneal dialysate from patients on continuous ambulatory peritoneal dialysis (CAPD). Peritoneal drainage during CAPD removes bacterial contaminants from the peritoneal cavity with an efficiency that depends upon the volume of peritoneal fluid remaining after drainage (residual volume). Combination of our data on the growth of coagulase-negative staphylococci in dialysate with a mathematical model of peritoneal drainage during CAPD shows that a residual volume of less than 800 ml (normal = approximately 400 ml) will prevent survival in the peritoneal fluid. A residual volume of less than 200 ml is required to eliminate S. aureus because of its faster rate of growth in dialysate. Previous work has shown that numbers of macrophages are too few to influence bacterial growth in the peritoneal dialysate. Coagulase-negative staphylococci adhere poorly to mesothelial cells in culture. Survival within the peritoneal cavity during CAPD probably depends on colonization of the PD catheter. Coagulase-negative staphylococcal peritonitis is likely to be localized to areas of the peritoneal membrane in close contact with the PD catheter. S. aureus is able to multiply in the peritoneal dialysate during CAPD and thereby causes generalized peritonitis.

Drainage↗
PubMed1992

The importance of thiopurine methyltransferase activity for the use of azathioprine in transplant recipients.

The immunosuppressive efficacy of azathioprine is related to its rapid metabolism in vivo to 6-mercaptopurine (6MP), with subsequent conversion to thioguanine nucleotides by an anabolic route involving hypoxanthine-guanine phosphoribosyltransferase. Two alternative catabolic routes exist: oxidation to 6-thiouric acid via xanthine oxidase and methylation to 6-methylmercaptopurine via the enzyme thiopurine methyltransferase (TPMT). Catabolism via either route would restrict formation of the active metabolites. We analyzed TPMT activity in erythrocyte lysates of 25 controls, 25 uremic patients on dialysis, and 68 transplanted patients. Median activity was lower in controls (31.0 pmol/hr/mg Hb, range 16.2-43.0) and transplanted patients receiving only cyclosporine and prednisolone (31.7 pmol/hr/mg Hb, range 12.7-43.5) than in the azathioprine treated group, (36.1 pmol/hr/mg Hb, range 16.1-71.3), or the uremic group on dialysis, (35.5 pmol/hr/mg Hb, range 18.6-62.6) suggesting that both azathioprine and uremia induce the enzyme, but CsA does not. Only 3 patients demonstrated total intolerance to azathioprine, 2 of whom had very low TPMT activity (zero and 12.7 pmol/hr/mg Hb). The intolerance of the third patient, despite high TPMT activity, was attributed to concomitant cotrimoxazole therapy. Patients with intermediate activity (15-26 pmol/hr/mg Hb) could tolerate azathioprine well. Of 29 cadaver recipients given only azathioprine plus prednisolone, 24 with a better clinical outcome had a significantly lower activity (33.1 pmol/hr/mg Hb, range 16.1-46.1) than 5 with reduced allograft function (42.5 pmol/hr/mg Hb, range 33.8-51.5). TPMT activity in these 24 patients was also significantly lower than the general group of azathioprine-treated recipients. This inverse association between TPMT activity and allograft function was again found among 30 patients receiving triple therapy (azathioprine, CsA, prednisolone). Self-selection of the best recipients for azathioprine immunosuppression apparently occurred, based on low catabolism of the drug. We conclude that total intolerance to azathioprine is rare and usually appears in patients with very low TPMT activities. Our results also suggest that the wide range of TPMT activity may be an important factor in determining long-term graft survival in azathioprine-treated patients; those with high activity might benefit from doses near the upper limit generally recommended.

Adolescent↗
PubMed1992

In situ expression of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 receptors in renal allograft biopsies.

The production and release of cytokines and their receptors are of critical importance in mediating graft injury. In order to evaluate the expression of cytokines in renal allograft biopsies, we performed immunocytochemical studies to detect activated cells positive for TNF-alpha, IFN-gamma, and IL-2R, using an alkaline phosphatase anti-alkaline phosphatase technique (APAAP). Sixty-one biopsy specimens from renal transplant patients were analyzed and were classified according to both clinical and conventional morphological criteria. There was a significant correlation between the number of positive cells reactive with monoclonal antibodies directed against TNF-alpha, IFN-gamma, and IL-2R and the presence of acute cellular rejection. The mean number of infiltrating cells (cells/mm2) positive for TNF-alpha (9.2 +/- 1.1), IFN-gamma (6.7 +/- 1.7), and IL-2R (31.2 +/- 4.8) was significantly greater in acute cellular rejection episodes compared with nonrejecting kidneys (0.9 +/- 0.2, 1.2 +/- 0.4, and 8.8 +/- 2.9 positive cells/mm2 for TNF-alpha, IFN-gamma, and IL-2R, respectively). No significant expression of these cytokines was found in the majority of biopsies with chronic rejection. In two cases, in which acute cellular rejection was not sustained on clinical grounds but was diagnosed on histology, the expression of TNF-alpha, IFN-gamma, and IL-2R was similar to that observed in typical cellular rejection. We conclude that TNF-alpha, IFN-gamma, and IL-2R are markedly expressed by activated mononuclear infiltrating cells in acute cellular rejection, and that these cytokines play an important role in allograft rejection. The immunocytochemical evaluation of cytokine expression is a simple and rapid method that is helpful in differentiating acute cellular rejection from other causes of graft disfunction.

Adolescent↗
PubMed1992

Different mechanisms by which anti-DNA MoAbs bind to human endothelial cells and glomerular mesangial cells.

The mechanisms by which anti-DNA MoAbs derived from MRL-lpr/lpr mice, bind to human umbilical vein endothelial cells (HUVEC) and glomerular mesangial cells were studied using a cellular ELISA. DNAse-treatment of either the MoAb or HUVEC followed by reconstitution with DNA and/or histones was performed to determine whether DNA and histones mediated such binding. It was found that MoAb410 bound to HUVEC and mesangial cells in the form of preformed DNA/anti-DNA immune complex, and such binding was facilitated by histones. In contrast, MoAb 152 bound directly to cell membrane-associated DNA, and adding DNA to MoAb 152 reduced its cellular binding. DNA binds endothelial cell surface and histones enhance the binding of both MoAb 410 and MoAb 152 to HUVEC by increasing cell membrane-associated DNA. Finally, the degree of MoAb binding to HUVEC is critically influenced by the relative concentrations of antibody, DNA, and histones.

Antibodies, Antinuclear↗
PubMed1992

Membranous nephropathy and its treatment.

Membranous nephropathy is a histological appearance which indicates a particular immunopathogenesis, but may have many basic aetiologies and is probably not a single disease. It is predominantly an appearance seen in middle-aged and elderly individuals, and in general has a slow progression over years or even decades towards remission or renal impairment in almost equal proportions. An aggressive search for associated disease is worthwhile, and one should wait to see what the evolution of proteinuria and renal function may be. If a progressive course becomes evident, then a trial of treatment with corticosteroids is worthwhile, but if this is ineffective, a more aggressive approach involving the use of alkylating agents may be justified. Cyclosporin does not appear to have a major effect in the majority of patients, and intravenous gammaglobulin is under evaluation at the moment with some encouraging results. The best treatment regime remains to be determined.

Adrenal Cortex Hormones↗
PubMed1992

Effects of diazoxide and glyburide on ATP-sensitive K+ channels from hypertrophied ventricular myocytes.

Hyperpolarizing vasodilators that specifically activate ATP-sensitive K+ currents (IK(ATP] in smooth muscle have been suggested as promising antihypertensive (if potentially arrhythmogenic and/or hyperglycemic) therapy. To date, however, the effects of agents presumed to influence these channels have not been characterized in hypertrophied cardiac muscle secondary to chronic hypertension. We used standard intracellular and patch clamp, single-channel recording techniques to study the effects of diazoxide, a presumed activator, as well as the sulfonylurea glyburide on IK(ATP) in cardiac muscle from control (WKY) and spontaneously hypertensive rats (SHR). Intracellular recordings were obtained from isolated left ventricles at 37 degrees C; unitary currents were recorded in excised, inside-out membrane patches with symmetrical transmembrane K+ at 21-23 degrees C. Diazoxide (5-100 microM) caused a decrease in action potential duration in both WKY and SHR ventricles. Glyburide (5-25 microM) produced dramatic dose-dependent increases in action potential duration approaching 100% in both groups. Action potential amplitude and resting membrane potential were unaffected by either agent. Before drug administration, unitary currents in hypertrophied myocytes exhibited a greater open state probability upon depolarization than those from control myocytes, although conductance, mean single-channel open time, and the number of channels per patch were not significantly different. Under patch clamp, both diazoxide (25 and 100 microM) and glyburide (50 microM) decreased IK(ATP) activity in cells from WKY and SHR in the absence of ATP. In both groups, the response reflected an overall decrease in open state probability. These data indicate that although IK(ATP) characteristics are altered in hypertension and myocardial hypertrophy, the effects of agents specific to this current are not significantly different in cells from SHR relative to control. On the other hand, the effects of diazoxide may be linked to temperature or to the metabolic state of the cell.

Adenosine Diphosphate↗
PubMed1991

New horizons in renal vasculitis.

After a long period during which few new data on the vasculitides emerged, the past decade has seen a real explosion of data on the subject. This began with basic clinical descriptions and the delineation of long term outcome as survival improved to a major extent under the influence of improved treatment regimes. In parallel, better understanding of the immunopathology has emerged. Of particular interest have been descriptions of autoantibody systems in vasculitis which seem to be specific to vasculitis and therefore diagnostically useful: the antineutrophil cytoplasmic antibodies (ANCA). Whether or not these are pathogenetically significant as well as useful remains a matter for debate. In parallel, anti endothelial cell antibodies have been described, but their role (if any), in pathogenesis remains equally obscure. There are some suggestions that vasculitis is becoming more common, but increased awareness and the availability of ANCA have undoubtedly increased awareness of the subject.

Autoimmune Diseases↗
PubMed1991

Recurrent primary disease and de novo nephritis following renal transplantation.

Recurrent or de novo diseases account for only 5% of graft failure in children, but have much to teach us about mechanisms. In children, almost the only metabolic disease with recurrence is type I hyperoxaluria, in which the poor long-term results of isolated renal transplantation make combined liver and renal transplantation, or even prophylactic liver transplantation before renal failure the preferable alternatives. While many forms of nephritis may show histological recurrence in allografts, it is notable that in many patients this is accompanied by no clinical manifestations or only mild disease: this is particularly so in mesangiocapillary glomerulonephritis (MCGN) type II. IgA-associated nephropathy and Henoch-Schönlein purpura. However focal segmental glomerulosclerosis and MCGN type I recur with sufficient frequency and severity to deter the use of living donors unless there is no alternative. The same is true of haemolytic-uraemic syndromes. As many as 10% of paediatric grafts may show de novo membranous nephropathy, but in the majority this is mild or not clinically evident. In contrast, the rare anti-glomerular basement membrane nephritis affecting some patients with Alport's syndrome usually results in graft failure, but occurs in only a minority of recipients with the syndrome. For all types of disease in allografts, risk factors for recurrence are poorly worked out, and attempts at treatment generally ineffective.

Amyloidosis↗