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J S Cameron

Publications and source records attributed to J S Cameron.

At least 127 records · Page 7Linked to original sources
PubMed1990

Enhanced susceptibility to histamine-induced cardiac arrhythmias in spontaneously hypertensive rats.

To clarify mechanisms underlying an enhanced susceptibility to cardiac rhythm disturbances in hypertension and myocardial hypertrophy, we evaluated the vulnerability to histamine-induced arrhythmias of isolated left ventricles from spontaneously hypertensive rats (SHR) and age-matched controls (Wistar-Kyoto rats, WKY). Before drug administration, left ventricle-to-body weight ratios, spontaneous firing rates, and the incidence of arrhythmias (including delayed afterdepolarizations) were significantly increased in SHR ventricles versus WKY. In addition, action potential duration (APD) was prolonged in SHR at all levels of repolarization. In WKY but not SHR hearts, histamine (10(-7)-10(-4) M) increased spontaneous firing rates; the incidence of arrhythmias was increased in all hearts, but the response to histamine was most pronounced and occurred at lower threshold drug levels in SHR. After potentials and triggered activity were observed only in SHR. The H2-receptor blocker cimetidine (10(-5) M) and the Ca2(+)-channel antagonist verapamil (10(-6) M) each attenuated the arrhythmogenic influence of histamine in SHR and WKY preparations. Neither chlorpheniramine nor propranolol had any effect. The enhanced vulnerability to arrhythmogenesis observed in SHR myocardium may reflect elevated intracellular calcium levels, which may in turn be potentiated by local ischemia and/or intracardiac histamine release.

Action Potentials↗
PubMed1990

Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis.

The interaction of circulating autoantibodies with the endothelium may be an important mechanism in the pathogenesis of systemic vasculitis. In a prospective study, we looked for circulating antiendothelial cell autoantibodies (AECA) and anti-neutrophil cytoplasm autoantibodies (ANCA) in 80 patients with suspected systemic vasculitis. AECA were measured using an isotype-specific cellular ELISA incorporating human umbilical vein endothelial cells. ANCA activity was determined by indirect immunofluorescence and radioimmunoassay. Sequential studies were performed on sera from four cases with dual positivity, where autoantibody binding was compared with von Willebrand factor (vWF) concentration and disease activity. IgG AECA were significantly higher in the 27 ANCA-positive sera as compared with normal controls (P = 0.027) with IgG (P = 0.009) and IgA (P = 0.046) AECA isotypes correlating with ANCA positivity; in contrast, no differences were found between AECA levels in the ANCA-negative sera and the normal controls. Cross-inhibition studies pointed to the co-existence of two autoantibody populations. An association between autoantibody binding, disease activity and vWF concentration was found for both ANCA and AECA. Some patients with systemic vasculitis have detectable AECA that recognize different epitopes to ANCA and like ANCA, their titre correlates with disease activity and thus they may have a pathogenetic role in these conditions.

Antibody Specificity↗
PubMed1990

Proteinuria and progression in human glomerular diseases.

Proteinuria is characteristic of many glomerular conditions, and often exceeds 2-3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies.

Animals↗
PubMed1990

Peritoneal defence mechanisms and Staphylococcus aureus in patients treated with continuous ambulatory peritoneal dialysis (CAPD).

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to S. aureus is associated with an adverse clinical outcome, suggesting impaired clearance of this organism by the host. The ability of peritoneal macrophages (PM0) derived from CAPD patients to take up S. aureus and mount a respiratory burst was investigated. Whilst significant activity was observed in the absence of opsonin, both parameters of phagocytosis were augmented by addition of 20% pooled human serum (PHS), complement-depleted PHS, and fibronectin. When used as sole opsonin, fibronectin resulted in a dose-related increase in chemiluminescent response by both blood neutrophils and PM0. The opsonic activity of dialysis effluent, as judged by neutrophil chemiluminescence, correlated with IgG and fibronectin content, but not with complement as assessed by C3 levels. The addition of urokinase to dialysate improved its opsonic properties whilst having no effect on the activity of PHS-20%; this would suggest that the formation of fibrin in dialysate, promoted by S. aureus, interferes with phagocytosis. This and the low IgG, complement and fibronectin levels in dialysate may explain in part the relatively poor clearance of this organism from the peritoneum.

Dialysis Solutions↗
PubMed1990

The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.

We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.

Adult↗
PubMed1990

Precocious familial gout with reduced fractional urate clearance and normal purine enzymes.

Gout is primarily a disease of middle-aged males and is unusual in females and adolescent males. We describe 21 young men and women (mean age 28 years) referred because of precocious onset of gout or hyperuricaemia. Fifteen patients had a family history, but known hereditary causes of primary or secondary hyperuricaemia were excluded. A high proportion (14/21) also had reduced renal function, but there was no clear relationship between this and the hyperuricaemia. Only two patients were hypertensive. A striking abnormality was that the uric acid clearance relative to creatinine [FEur] was subnormal (mean 4.4 +/- 1.4 per cent) in 15/21 patients, including all seven females. A dominantly inherited defect in renal tubular urate handling, leading to a reduced endogenous urate clearance, is the most likely explanation for the hyperuricaemia in this group. Only six patients, all male had a normal [FEur] (mean 8.6 +/- 1.0 per cent). The results confirm that young men and women with gout-or hyperuricaemia disproportionate to the renal dysfunction-should always be investigated, not only for purine defects, but also for abnormalities of renal urate handling. Since the abnormality described here was found also in symptomless subjects, the families of such patients must also be studied. Early identification is important since treatment may ameliorate the renal damage. Although rare, the number of such patients seen in a single referral unit suggests that this type of renal tubular defect in urate handling is more common than suspected and may only come to attention through an isolated episode of precocious gout, when renal function may already be impaired.

Adolescent↗
PubMed1989

Histamine attenuates the arrhythmogenic effects of norepinephrine in hearts of spontaneously hypertensive rats.

A potential physiological role for cardiac histamine and its interaction with norepinephrine were investigated in isolated left ventricles from spontaneously hypertensive rats (SHR). Prior to drug administration, left ventricle-to-body weight ratios and spontaneous firing rates (beats per min) were significantly increased in SHR ventricles vs. age- and sex-matched controls (WKY). Also, action potential duration was significantly prolonged in SHR at all levels of repolarization. In all hearts, norepinephrine (10(-7)-10(-4) M) increased spontaneous rate and the percent incidence of arrhythmias. The H2-receptor antagonist cimetidine (10(-5) M) potentiated the rate and arrhythmogenic effects of norepinephrine in SHR and, to a lesser extent, in WKY preparations; propranolol (10(-6) M) reduced them. Histamine (10(-7) M) also inhibited the norepinephrine-induced increase in arrhythmias in SHR, but not in WKY. The attenuation of adrenergically induced rhythm disturbances by histamine and their potentiation by cimetidine in hypertensive hearts support the hypothesis that histamine plays a role as a postjunctional modulator of adrenoceptor function in a setting of hypertension and myocardial hypertrophy.

Action Potentials↗
PubMed1989

Purine enzyme defects as a cause of acute renal failure in childhood.

Acute renal failure (ARF) is not listed as a usual form of presentation in hypoxanthine-guanine phosphoribosyltransferase deficiency, despite the gross uric acid overproduction in the defect. We found that a third of such patients may present in ARF when the urinary uric acid/creatinine ratio may be normal, not raised, and the defect may be suspected from the disproportionate increase in plasma uric acid. This is important in view of the potential confusion of uric acid with 2,8-dihydroxyadenine, the even more insoluble purine excreted in the other salvage enzyme disorder, adenine phosphoribosyltransferase deficiency. In that disorder, presentation in ARF is well recognized, the uric acid/creatinine ratio is also normal, but plasma urate is not raised. Our combined experience in these two disorders underlines the importance of early recognition and treatment with carefully adjusted doses of allopurinol, which may reverse or postpone renal failure.

Acute Kidney Injury↗
PubMed1989

The treatment of lupus nephritis.

The literature on the treatment of lupus nephritis is scattered, much of it in rheumatological rather than nephrological journals. Whatever our ignorance of the nature and genesis of lupus nephritis, under empirical treatment the prognosis, especially for severe forms, has improved dramatically during the past 20 years. For severe lupus nephritis, the evidence that the addition of cytotoxic agents to corticosteroids improves outcome is now secure, and discussion centres mainly on which drug to use and by what route. Intravenous methylprednisolone is at least as effective as high-dose tapering oral therapy for initial treatment, and carries fewer side-effects. The role of plasma exchange in lupus remains undefined: it may have a role in the treatment of cerebral manifestations or otherwise resistant patients, but controlled trials have failed to show benefit. Future developments will probably centre around the use of specific monoclonal antibodies which target specific groups and subgroups of cells, "humanised" by the splicing of human Fc piece to rodent (fab)2, perhaps bearing toxins. To use these agents to best advantage, however, we will have to understand better than we do today the nature of the cellular defects in the immune response which underlie the lupus syndrome.

Child↗
PubMed1989

Immune mechanisms in idiopathic membranous nephropathy: the role of the interstitial infiltrates.

Mononuclear inflammatory cells in renal biopsies from 36 patients with membranous nephropathy (MN) were analyzed, using monoclonal antibodies. In the interstitium, monocytes/macrophages and T cells were the predominant cell types (210 +/- 27 and 171 +/- 25/mm2, respectively); in contrast, very few intraglomerular leucocytes, mostly macrophages (1.0 +/- 0.7 cell/glomerular cross-section), were found. Among the interstitial T-cell population, helper/inducer cells (CD4+) predominated (CD4:CD8 ratio, 2.2 +/- 1.5). Natural killer (NK) cells and B lymphocytes were a minor component of the interstitial infiltrates and were almost absent in the glomeruli. Significantly higher numbers of DR-expressing cells were found in the interstitium (322 +/- 20/mm2) than in controls (109 +/- 30), but tubular DR expression was similar to controls (17 +/- 12 mm2). The numbers of total leukocytes and their subsets CD4+, CD8+, monocytes/macrophages, and B cells all correlated with the degree of renal impairment at the time of biopsy, but surprisingly there was no correlation between interstitial cell numbers and the histological severity of tubulointerstitial lesions. Progressive renal impairment over 5 years was associated with many interstitial T cells and monocytes/macrophages in the initial biopsy. Our results suggest that interstitial mononuclear cells may be important determinants in the pathogenesis of MN. Both cellular and humoral immune mechanisms may play a major role in the initiation of the disease, whereas progression toward renal failure seems to be determined mainly by cell-mediated immunity.

Antibodies, Monoclonal↗
PubMed1989

Activation of immunocompetent cells in the peritoneum of patients treated with CAPD.

Chemiluminescence and flow cytometry, employing a number of monoclonal antibodies, was used to investigate activation of immunocompetent cells in the blood and peritoneum of patients treated with CAPD. Increased expression of HLA-DR and RFD7, both markers of macrophage maturation, was observed on peritoneal macrophages, 78% and 33.5% cells positive, when compared to blood monocytes, which were 46% and 5.3%, respectively (P less than 0.001). Macrophage chemiluminescent response to opsonized zymosan was greater than that of circulating blood monocytes in CAPD patients, whereas the inverse was true for normal controls. Enhanced expression of IL-2 receptor and surface IgG by peritoneal macrophages were 24.9% and 65.3% cells positive compared with monocytes, 5.7% and 12.3% (P less than 0.01), and also suggests their activation. There was a marked increase in the HLA-DR expression by peritoneal lymphocytes from CAPD patients (32% cells positive) compared with those from CAPD blood (13.8%), normal blood (11.3%) and normal peritoneal fluid (14.5%), P less than 0.001. This was partially accounted for by increased numbers of B cells (18%) and activated T cells bearing HLA-DR. TFR and IL-2 receptor expression by CAPD peritoneal lymphocytes was similar to that of blood lymphocytes, implying the lack of an organized immune response within the peritoneum. Taken together, these results suggest that peritoneal macrophages from CAPD treated patients have features of maturation and activation, while changes in the lymphocyte populations are compatable with the actions of IL-1, indicating activity of the cellular immune system within the peritoneum.

B-Lymphocytes↗
PubMed1989

The role of interstitial infiltrates in IgA nephropathy: a study with monoclonal antibodies.

The leucocyte subpopulations in the interstitium and the glomeruli in renal biopsies from 34 patients with IgA nephropathy were analysed using monoclonal antibodies and immunoperoxidase techniques. Monocyte/macrophages and T-cells constituted the predominant infiltrating cell type in the interstitium (278 +/- 24 and 269 +/- 37 cells/mm2 respectively). Few intraglomerular leucocytes were seen, the majority of them belonging to the monocyte/macrophage phenotype (1.1 +/- 0.1 cells/glomerular cross-section). CD4+ lymphocytes predominated among the interstitial and glomerular T-cell populations and the CD4:CD8 ratio was 2.1 +/- 1.1 and 2.4 +/- 1.5 respectively. Only small numbers of NK cells and B cells were found in the interstitium, and almost none in the glomeruli. In contrast, significantly increased numbers of DR-expressing interstitial cells were seen (487 +/- 29/mm2), whereas DR expression by the tubular cells was minimal (37 +/- 6/mm2). Numbers of total leukocytes and T-cells were well correlated with the degree of tubulointerstitial damage and there was a significant correlation between renal functional impairment at the time of biopsy and the numbers of interstitial T cells (P less than 0.05) and CD4+ T cells (P less than 0.01). In contrast, interstitial mononuclear cells did not correlate with subsequent progression of the disease over 2-3 years. However, a more rapid decline of renal function was associated with increased numbers of interstitial B cells. No association was found between intraglomerular cells and degree of renal impairment either at the time of biopsy or in the long term.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

HLA-DR display by renal tubular epithelium and phenotype of infiltrate in interstitial nephritis.

Renal tubular display of HLA-DR was estimated semi-quantitatively in 28 biopsies from 27 patients with various forms of tubulointerstitial nephritis (10 following use of non-steroidal anti-inflammatory drugs) using a monoclonal anti-MHC class II non-polymorphic antibody (DK-22). Normal donor kidneys and biopsies from patients with minimal-change nephrotic syndrome were examined as controls. The phenotype of infiltrating cells was also studied quantitatively, using monoclonal antibodies on frozen biopsy tissue; the number of cells infiltrating the interstitium was counted per tubular cross-section. Display of HLA-DR was seen in up to 5% of control tubular cells, but up to 100% expressed HLA-DR in tubulointerstitial nephritis biopsies. There was a correlation between the expression of HLA-DR and the severity of both tubular atrophy and tubulointerstitial fibrosis judged semi-quantitatively by optical microscopy. In controls up to 50 leucocytes per tubular cross-section were evident, but in patients with tubulointerstitial nephritis up to 1500 were observed, approximately 50% being T-lymphocytes, the majority expressing the helper phenotype except in early, active drug-induced tubulointerstitial nephritis; the remainder were mostly monocytes. There were no qualitative differences between the different causes of tubulointerstitial nephritis. Tubular DR expression correlated with the number of DR-positive cells in the interstitium, but not with total leucocytes or T-lymphocytes. HLA-DR tubular expression was greater in the early stages than late stages of NSAID-induced tubulointerstitial nephritis, but this relationship was not present in the group as whole. HLA-DR expression by renal tubular epithelial cells may play a role in localising or amplifying tubular injury in tubulointerstitial nephritis.

Adolescent↗