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Biomedical subjects

A R Clarkson

Publications and source records attributed to A R Clarkson.

At least 55 records · Page 3Linked to original sources
PubMed1987

Increased concentration of serum IgA antibody to pneumococcal polysaccharides in patients with IgA nephropathy.

It has been postulated that IgA nephropathy (IgAGN) is caused by deposition within the glomerular mesangium of IgA polymers and IgA containing immune complexes which are overproduced in response to antigens presented at mucosal surfaces. To test this, the concentrations of specific antibodies to capsular polysaccharides from pneumococci, which are common commensal and/or pathogenic bacteria in the respiratory tract, have been measured. Sera from 35 patients with IgAGN, six with systemic lupus erythematosus (SLE), eight with membranous glomerulonephritis (MGN) and six with Goodpasture's syndrome (GPS), and from 20 controls (C) were assayed. The concentrations of IgG and IgA antibodies specific for each of five pneumococcal polysaccharides (serotypes 2, 7F, 9N, 14 and 23F) were determined by ELISA. The results from the SLE, MGN and GPS patients were pooled and used as a control group of patients with forms of nephritis other than IgAGN (patient controls, PC). Groups were compared using the Wilcoxon test or the Chi square test. There were no significant differences in the concentrations of IgG antibody to any of the serotypes between the IgAGN and normals, but the PC sera had significantly lower concentrations than either the IgAGN or normals. By contrast, there were no differences between the PC and C in the proportion with detectable IgA antibody to four of the serotypes, but this was significantly increased in IgAGN. There was insufficient IgA antibody to serotype 2 to detect in the assay system used. It is concluded that IgAGN patients have greater concentrations of IgA antibodies, but not IgG, to these pneumococcal polysaccharides, compared with normal controls or patients with other forms of nephritis.

Adolescent↗
PubMed1986

Evidence for IgA-specific B cell hyperactivity in patients with IgA nephropathy.

Spontaneous in vitro IgA synthesis by peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy was elevated; 419 +/- 71 ng/10(6) cells (Mean +/- SEM) compared with controls; 217 +/- 35 (P less than 0.02). Pokeweed mitogen (PWM) stimulated IgA synthesis was also elevated in patients; 4326 +/- 1140 ng/10(6) cells (Mean +/- SEM) versus 1458 +/- 406 (P less than 0.02) but the PWM stimulation index for patients did not differ significantly from that of the controls. Concanavalin A (Con A) suppression of PWM stimulated IgA synthesis resulted in the generation of similar quantities of IgA by PBMC from both patients and controls but the percentage suppression was significantly elevated in patients; 87 +/- 5 (Mean +/- SEM) versus 58 +/- 10 (P less than 0.05). Synthesis of IgG and IgM followed the same pattern as that described for IgA. T and B cells from patients and controls were cultured alone and in various co-culture permutations. Enriched B cells of patients demonstrated a selectively increased capacity for IgA production; 266 +/- 106 ng/5 X 10(5) cells (Mean +/- SEM) compared with controls; 42 +/- 9 (P less than 0.01) and this parameter correlated significantly with serum IgA concentrations (R = 0.77, P less than 0.05). Overall analysis of co-culture data showed no significant difference between the influences of autologous, control or patient T cells on immunoglobulin synthesis by normal B cells. Autolymphocytotoxic antibodies were not detected and, compared with controls, patient sera had no differential effect on numbers of IgA producing cells generated in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Correlation of paramesangial deposits and glomerular sclerosis and/or hyalinosis in patients with IgA nephropathy.

Correlation of paramesangial deposits ("hemispherical body") and glomerular sclerosis and/or hyalinosis was examined by light microscopical analysis in 40 patients of IgA nephropathy. Correlation of paramesangial deposits and intensity of IgA or C3 deposition in glomeruli was also evaluated in these patients. The number of paramesangial deposits was markedly increased in patients with moderate and advanced stages of IgA nephropathy who showed marked glomerular sclerosis and/or hyalinosis. There was a significant correlation between the number of paramesangial deposits and the intensity of IgA deposits in glomeruli. It is suggested that the accumulation of paramesangial deposits might induce severe glomerular injuries such as glomerular sclerosis and/or hyalinosis.

Complement C3↗
PubMed1985

IgA nephropathy--accumulated experience and current concepts.

Primary IgA nephropathy is the most common form of glomerulonephritis in Australia. The condition presents in a variety of ways, but commonly with synpharyngitic hematuria, most often in young men in the third and fourth decades. The course of the disease is indolent but there is progression to renal failure in up to one quarter of cases. Renal biopsy morphology is variable but the essential immunofluorescence finding is diffuse mesangial IgA staining of greater intensity but often in association with other immunoglobulins. C3 is usually also present. Mesangial cellularity is increased in some two-thirds of cases, one third being of a minor focal or variable extent and one-third diffuse. Focal segmental lesions, hyaline nodules and vascular changes are frequent. Crescents are also often present. The etiology of the disease is uncertain but has been linked with HLA antigens, elevated serum IgA levels, IgA polymers, immune complexes and impaired T cell function. Secondary forms of mesangial IgA deposition occur with mucosal defects, hyperglobulinemia or impaired hepatobiliary clearance, and these may offer some insight into the immunopathogenesis of the primary disease.

Adolescent↗
PubMed1984

Reconstructive renal vascular surgery for chronic renal failure.

This paper reports the results of reconstructive renal arterial operations on 23 patients who underwent surgery because it was considered that renal artery disease was contributing to their chronic renal failure. The median pre-operative serum creatinine in this group of patients was 0.77 (range 0.15-1.14 mmol/l) and all patients had severe hypertension. In 10 cases there was evidence of other renal disease (analgesic nephropathy, 8; glomerulonephritis, 2). Operation performed was unilateral aortorenal reconstruction in 21 patients and bilateral reconstruction in 2 patients. There were four in-hospital deaths. In 15 patients operation was judged to have improved their renal function with a fall of median pre-operative creatinine from 0.34 mmol/l (0.15-0.84) to a median creatinine of 0.15 (0.05-0.52). There was one intra-operative death. There were 7 patients in whom operation led to no improvement in renal function. Their median pre-operative creatinine was 0.90 (0.32-1.14 mmol/l), and this pre-operative creatinine differs significantly from the group whose creatinine fell after surgery (P less than 0.002). Renal artery reconstruction should be considered in patients with chronic renal failure who have correctable arterial lesions.

Adult↗
PubMed1984

Fc-specific reticulo-endothelial clearance in systemic lupus erythematosus and glomerulonephritis.

Fc-specific reticulo-endothelial (R-E) clearance was determined in control subjects (n = 11) and in patients with immune complex (IC) glomerulonephritis (n = 22) and systemic lupus erythematosus (SLE) nephritis (n = 10). Clearance (t1/2) depended on the removal of autologous erythrocytes labeled with 51chromium and sensitized with anti-D IgG by fixed splenic macrophages bearing receptors for the Fc portion of the IgG molecule. A significant difference in clearance rates was demonstrated between normal individuals with and without the HLA-B8, DR3 haplotype. Marked clearance defects were found in SLE (8/10), and t1/2 correlated with the levels of circulating IC. Delayed clearance was also observed in 6/11 patients with IgA nephropathy or Henoch-Schönlein purpura and in 4/11 patients with membranous nephropathy (MN). No correlation was found between circulating IC levels and t1/2 in these diseases. Clearance defects in these patients did not correlate with the presence of the HLA-B8, DR3 haplotype. This study demonstrates that some patients with IC glomerulonephritis have defective Fc-mediated clearance that does not appear to be secondary to IC blockade.

Adult↗
PubMed1984

Giardiasis in intensively reared Saanen kids.

Outbreaks of diarrhoea in two groups of Saanen.kids aged 4 to 6 weeks were ascribed to giardiasis, although Cryptosporidia were also present. In all, 45 out of 65 kids were affected, two animals died, and the remainder eventually recovered. Aspects of the epidemiology and diagnosis of giardiasis are discussed. Air dried smears prepared from small intenstinal mucosa, intestinal contents, or freshly-voided faeces proved to be suitable for making a diagnosis, and are the recommended sample when laboratory examination will be delayed beyond a few hours.

Journal Article↗
PubMed1984

Changes in plasma catecholamine levels during hemodialysis.

The plasma concentrations of dopamine (DA), adrenaline (AD) and noradrenaline (NA) were measured during 29 routine hemodialysis (HD) treatments on 13 patients to determine whether any changes occurred in the concentrations of these substances during HD. All of the 13 patients studied demonstrated a fall in mean arterial pressure (MAP) when HD was commenced. Decreased concentrations of all three catecholamines were also demonstrated after the first hour of dialysis. Plasma AD rose after two hours, but NA and DA were still significantly lower than pre-dialysis values at the end of HD. Study of 12 further patients during the first hour of HD confirmed that the NA level had fallen significantly by the fifteenth minute of HD, while the DA and AD levels took somewhat longer to fall. Both NA and DA were present in the dialysate in substantial amounts. Although the fall in MAP which accompanies HD is probably multifactorial, the loss of plasma catecholamines during HD may possibly contribute to the hemodynamic changes.

Adult↗
PubMed1984

The syndrome of IgA nephropathy.

A review is presented of the current knowledge concerning the syndrome of IgA nephropathy. Primary and secondary forms can now be delineated and this division has improved understanding of immunopathogenetic mechanisms giving rise to glomerular mesangial IgA deposits. Attention is paid to disorders of antigen exclusion at mucosal surfaces, defective reticulo-endothelial sequestration, and altered immunoglobulin A production and regulation. Particular reference is made to these mechanisms with respect to primary IgA nephropathy, Henoch-Schoenlein purpura and mesangial IgA nephritis associated with alcoholic cirrhosis.

Adolescent↗
PubMed1983

Glomerulonephritis.

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Antigen-Antibody Complex↗
PubMed1983

Renal complications of cytotoxic therapy.

The expanding use of cytotoxic drugs in cancer therapy has resulted in a confusing and increasingly frequent array of severe renal complications. This article reviews the nephrotoxicity and other renal and urological complications of commonly used drugs and the clinical setting in which they are prescribed. Emphasis is placed on the mechanisms, prevention and treatment of renal damage.

Animals↗
PubMed1983

Immunoregulation in glomerulonephritis, Henoch--Schonlein purpura and lupus nephritis.

Immunoregulation was examined in normal controls and in patients with immune complex glomerulonephritis and lupus nephritis (SLE) using OKT monoclonal anti-bodies against helper (OKT4) and suppressor (OKT8) T cell subsets. Functional studies assessed T cell control of in vitro immunoglobulin synthesis by cultured peripheral blood mononuclear cells (PBMC). IgG and IgA synthesis was measured in unstimulated, pokeweed mitogen (PWM) stimulated and PWM + concanavalin A (Con A) stimulated cultures. Patients with primary membranous nephropathy (MN) and mesangial IgA nephropathy (IgA GN) were found to have elevated T4/T8 ratios secondary to a deficiency of the T8+ subset. Patients with SLE had low T4/T8 ratios. B cell activation with high spontaneous immunoglobulin synthesis was present in cell cultures from patients with SLE, IgA GN and Henoch-Schonlein purpura (HSP). Defective Con A inducible suppression of in vitro immunoglobulin synthesis was found in SLE, HSP and to a lesser extent, primary MN. Functional Con A inducible suppressor defects correlated with elevated T4/T8 ratios only in patients with MN. All four disorders appear to share disturbances of cellular immune response with various degrees of defective immune suppression; however, it is not clear from these studies whether the defects are primary or secondary phenomena.

Adult↗
PubMed1983

Glomerular IgG subclass distribution in human glomerulonephritis.

IgG subclass distribution was determined in glomerular immune deposits found in patients with membranous, mesangiocapillary, lupus and antiglomerular basement membrane antibody induced glomerulonephritis. In each disease category IgG3 was the predominant subclass found. In membranous, lupus and anti-glomerular basement membrane antibody induced nephritis the other subclasses were detected in significant but lesser amounts although in anti-glomerular basement membrane antibody induced nephritis IgG2 deposition was minimal. Particularly striking was the excess of IgG3 compared with other subclasses in mesangiocapillary glomerulonephritis and the greater amount of IgG4 in membranous glomeruli compared to the other disease categories. These findings indicate a difference between the distribution of IgG subclasses in normal plasma and glomerular immune deposits and may be of importance in the pathogenesis of the types of glomerulonephritis studied.

Fluorescent Antibody Technique↗
PubMed1982

Mesangial IgA nephritis.

Current data suggest that mesangial IgA nephritis is mediated by the mesangial deposition of soluble antigen-IgA class antibody complexes from the circulation. It is likely that common infectious gut flora and dietary antigens contribute to the immune complex load. Defects in antigen exclusion at the mucosa, in the control of IgA production, and in immune complex clearance are postulated to account for each of the recognized clinical syndromes. As yet no effective treatment is available, and a detailed analysis of the mediation pathways will be required before prevention or therapy can be attempted.

Adolescent↗
PubMed1982

Renal lesions in leptospirosis.

Renal function studies and kidney biopsies were performed in four patients presenting with renal insufficiency and acute Leptospira pomona infection. The renal lesion in all patients revealed acute interstitial nephritis. There was no evidence of immunologically mediated disease in three patients who were biopsied seven, eight and eight days respectively following the onset of symptoms. The fourth, in whom there was no evidence of prior renal disease, and whose biopsy was performed 16 days after symptoms began, showed glomerular Clq, and C3 immunofluorescence and mesangial, subepithelial and intramembranous dense deposits by electron microscopy. In addition, circulating immune complexes were demonstrated in this patient. These findings suggest that in this instance at least, the renal lesions of Leptospira pomona infections can be immunologically mediated. Because this may well be a transient phase, the timing of investigations could be crucial to its detection.

Adult↗