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Biomedical subjects

J A Charlesworth

Publications and source records attributed to J A Charlesworth.

14 recordsLinked to original sources
PubMed1992

The value of complement measurements in the assessment of lupus activity.

The complement system was studied prospectively in 29 patients, predominantly renal (25), with systemic lupus erythematosus (SLE) to examine the value of complement assays in the distinction between active and inactive disease. Disease activity was evaluated primarily by clinical, biochemical and histological parameters which were obtained at the time of assessment. Fourteen patients had active disease, as assessed by clinical and laboratory criteria. C1q, C4, C4a, C2, C3, C3a, C5, total haemolytic activity (CH50) and complement inhibitors were measured in each patient. The ratios of C4a:C4 and C3a:C3 were also calculated. Values for all components except C5 were different between control subjects and active patients while only CH50 was different between inactive patients and controls. All parameters except C4a:C4 and C5 were different between active and inactive patients. There was a highly significant difference in the number of active patients with reduced levels of C2, C3 and C3a:C3 compared to inactive patients (i.e. p less than 0.001) whereas lesser or no difference was observed for other parameters. The concentration of complement inhibitors was elevated in both groups. We conclude that, among readily available complement parameters, C2 and C3 provide the best assessment of disease activity in patients with SLE.

Adult↗
PubMed1979

Lipoprotein lipids in chronic renal failure and haemodialysis. The influence of etiology and implications for atherogenesis.

Lipoprotein lipid analysis has been carried out in 39 women and 28 men with chronic renal failure on haemodialysis. The results have been analysed in relation to the etiology of the renal disease and compared with those obtained in age- and sex-matched controls and in triglyceride-matched controls. Serum cholesterol was normal or low in glomerulonephritis but was normal in analgesic nephropathy. Serum triglycerides and VLDL lipids were raised uniformly regardless of the etiology of the renal disease. LDL triglyceride and HDL triglyceride were also raised. LDL cholesterol and phospholipid were low in glomerulonephritis but were normal in analgesic nephropathy. HDL cholesterol was reduced in both male and female patients regardless of etiology, statistical significance was not reached for the women. The ratio of esterified to free cholesterol tended to be reduced in all the lipoproteins regardless of sex or etiology but the changes were not significant in all groups. Comparison of the lipid abnormalities with those found in other hyperlipidaemic states suggests that the lipid disorders found in chronic renal failure are probably insufficient to explain the rapid development of vascular disease which has been reported.

Adult↗
PubMed1979

Immune complexes in diabetes mellitus.

Sera from 86 well controlled diabetics were examined for the presence of immune complexes. Thirty-six patients were receiving standard insulins, 19 monocomponent preparations, 24 oral hypoglycaemic agents and seven dietary restriction alone. Three methods were used to detect complexes: measurement of complement components, a Clq binding assay (BA) and the Raji cell radioimmunoassay (RIA). Complement components were normal in all patients. Eleven (31%) of the group on standard insulins had a positive Raji cell RIA; none had an abnormal Clq-BA. One patient on monocomponent therapy had a mildly positive Raji cell RIA; Clq-BA was negative in each patient of this group. Thirteen (54%) of the patients on oral hypoglycaemic agents were positive on one or both assays while one patient on diet alone was abnormal on both assays. These data show that immune complex production is common in both insulin-requiring and non-insulin-requiring diabetics and that this phenomenon is strikingly less frequent in patients on monocomponent insulins. Such observations could bear relevance to the pathogenesis of microvascular complications in diabetes.

Adolescent↗
PubMed1979

The detection of immune complexes of different immunoglobulin class.

Immune complexes were detected in 51 sera from patients with a variety of immunological diseases; 14 systemic lupus erythematosus (SLE); 14 infectious mononucleosis (IM); 12 rheumatoid arthritis (RA) and 11 subacute bacterial endocarditis (SBE). Three methods were used to detect complexes: the fluid--phase Clq binding assay (Clq.BA); the solid--phaseClq binding assay (Clq.SP) and the Raji cell radio-immunoassay (RIA). Modification of the Clq.SP and the Raji cell RIA by use of monospecific antisera to immunoglobulins G, A and M enabled the class of antibody in the immune complexes to be determined. Antibodies of all three classes were found in each disease, the predominant ones being IgG and IgM in SLE and SBE, IgM and IgA in RA and IgM in IM.

Adult↗
PubMed1979

Impairment of acute protein reactivity in chronic renal failure.

The acute phase protein response was studied after elective surgery in 13 normal subjects and 9 patients with severe chronic renal failure. Total haemolytic complement reactivity (CH50) and serum concentrations of C1q, C1s, C4, C3, factor B, properdin, C5, C9, C-reactive protein (CRP), caeruloplasmin, alpha1-acid glycoprotein and haptoglobin were measured preoperatively and on days 2, 4 and 6 after operation. Abnormalities were seen in the group with chronic renal failure. Firstly, there was no significant acute phase response of C1s, C3, C5, C9 and CH50 and a significant reduction in the response of factor B. Secondly, CRP showed prolonged elevation in the post-operative period in contrast to the transient rise seen in the control group. With the possible exception of alpha1-acid glycoprotein, the behaviour of the non-complement proteins (caeruloplasmin and haptoglobin) was comparable for the two groups. These defects could impair the physiological response to infection in patients with severe chronic renal failure.

Adult↗
PubMed1979

Metabolism of human beta 1H: studies in man and experimental animals.

Metabolic studies were performed with a purified, functionally-active preparation of human beta 1H. In seven normal human subjects, the half-life ranged from 66--87 hr with fractional catabolic rates (FCR) of 1.04--1.63%/hr. Synthesis rates were 0.22--0.57 mg/kg/hr and extravascular distribution ratios were 0.34--0.67. There was evidence of extra-vascular catabolism in each subject. In sixteen patients with immunological disease four showed hypercatabolism of beta 1H. However, three patients with C3 mephritis factor (NeF) had normal beta 1H turnover despite profound reduction in C3 concentration; it is suggested that the reaction of beta 1H with the C3b. Bb convertase exposes it to a catabolic site and that in the NeF patients the NeF stabilized convertase prevents such exposure. Studies of the acute phase response were carried out in nine patients following elective surgery, with C-reactive protein (CRP) used as the control protein: six patients showed no rise in beta 1H levels and three showed a small (20%) rise whereas all exhibited a gross rise in CRP. Pre-incubation of 125I- beta 1H with NHS, with NHS in the presence of NeF and with C3b+C3b 1NA caused no change in beta 1H turnover in animals despite demonstrable total C3 conversion with the NeF.

Animals↗
PubMed1978

Angiography in the diagnosis of renal allograft dysfunction.

We reviewed retrospectively 75 renal transplant arteriograms done during a 7-year period. Acute rejection and vasomotor nephropathy were not differentiated. Generalized cortical ischemia was diagnosed correctly in 23 of 30 cases but there were 7 falsely negative results. Renal artery stenosis was found in 7 of 17 cases in which the main indication for arteriography was hypertension. We conclude that the major role of transplant arteriography is in the diagnosis of larger vessel disease.

Adolescent↗
PubMed1977

Complement activation in migraine.

Forty patients attending the Prince Henry Hospital migraine clinic have been investigated for evidence of complement activation related to migraine. These patients had a history of clinically similar migraine attacks. Levels of serum complement components were determined in nine patients, both in and out of migraine. Comparison of these levels showed significant reductions in C4 and C5 during headache. In a further 31 patients C3 breakdown products were sought when these patients were headache-free. They were detected in the plasma of three patients who proceeded to a migraine attack but not in the plasma of the remaining twenty-eight who did not. These findings suggest the presence of complement activation, which could explain many of the previously reported phenomena associated with migraine.

Complement C1↗
PubMed1977

The Nail Patella syndrome--a report of a family.

This report describes two cases of the Nail Patella Syndrome with renal involvement. Pathological studies include immunochemistry, light microscopy, immunofluorescence and electron microscopy. The possibility of secondary immune damage to altered glomerular basement membrane is suggested as a cause of the progressive renal disease which occurs in some of these cases.

Adolescent↗
PubMed1977

The complement system in infectious mononucleosis.

The complement system was investigated in 34 patients with infectious mononucleosis. Three had specific complications: one haemolytic anaemia, one severe arthralgia/myalgia and one proliferative glomerulonephritis. Complement changes consistent with classical pathway consumption were seen in ten of the uncomplicated group and the patients with haemolytic anaemia and arthralgia/myalgia. The patient with glomerulonephritis showed evidence of alternative pathway utilisation including C3 splitting activity and the deposition of properdin on renal biopsy. The complement findings suggest that circulating immune complexes are common in such patients and are likely to play a role in the pathogenesis of the complications. It is proposed that both complement pathways may be required for the effective clearance of viral material from the circulation.

Complement C1 Inactivator Proteins↗
PubMed1977

Acute hepatitis: significance of changes in complement components.

Serial measurements of complement components were performed in fifty-nine patients with acute, uncomplicated hepatitis and twelve with alcoholic cirrhosis. Thirty-one of the former group had detectable hepatitis B antigen. Abnormal complement profiles were observed in nine patients with hepatitis B and seven with antigen-negative hepatitis. Low levels of C4, C3 and factor B were common in the subjects with cirrhosis and confined to those cases with severe reduction in serum albumin and/or prothrombin index. By contrast, the complement changes in the patients with hepatitis occurred without significant alteration in these parameters; certain subjects also had reduction in C1q and C5 and a significant number had C3d detectable in fresh plasma. The pattern of abnormality suggests predominant involvement of the classical pathway and it is concluded that this results, at least in part, from an immune process evident only in the early clinical phase of hepatitis. Such gross changes in complement are likely to reflect immune-complex activity and it is proposed that these complexes may be important in the clearance of virus material. The data supports a previous suggestion that recovery from acute hepatitis is primarily dependent on host immune competence rather than viral cytotoxicity or generation of immune complexes.

Acute Disease↗
PubMed1976

Measles infection. Involvement of the complement system.

The complement system was examined in fifty patients with acute, apparently uncomplicated measles; forty-six were children less than 10 years old. Twenty showed evidence of pathological complement activation. In thirteen of these the pattern was consistent with activation of the classical pathway while in the other seven data suggested utilization of an alternative pathway. An additional eleven patients had isolated reduction in Clq without alteration in concentration of other components; these were excluded from the classical pathway group. No patient had detectable immune complexes or C3 splitting activity in serum; however, it is suggested that the abnormal complement patterns observed are likely to indicate the presence of circulating immune complexes in a high percentage of patients with this infection.

Antigen-Antibody Complex↗