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Biomedical subjects

R N Maini

Publications and source records attributed to R N Maini.

At least 307 records · Page 17Linked to original sources

The inhibitory effect of D-penicillamine on human lymphocyte cultures stimulated by phytohaemagglutinin, the antagonistic action of L-cysteine and synergistic inhibition by copper sulphate.

The inhibitory effects of D-penicillamine (D-Pen) on lymphocyte activation by PHA are found to be dose-dependent, showing significant effects above a concentration of 50 microgram/ml. The cells show a diminished sensitivity to D-Pen added after 24 hours in culture, although the dose-response relationship is maintained. L-cysteine is usually found to have an insignificant effect on PHA stimulation, although enhancement and inhibition are also sometimes observed. The supplementation of culture medium with L-cysteine abolishes the inhibitory effect of D-Pen, whilst copper sulphate synergistically inhibits PHA-induced transformation. The balance between the availability of naturally occurring thiols, copper ions and administered D-Pen may be critical in determining the eventual effect of the drug on the lymphoid system. Lymphocyte suppressive soluble factors appear in the sera of patients with rheumatoid arthritis and are modified by treatment with D-Pen. Although our experiments suggest possible modes of action of the drug on the immune system as a therapeutic agent as well as a potent inducer of autoimmunity in its own right, further work is required to delineate its precise mechanism of action.

Adult↗

The association of cryoglobulinaemia with nodules, vasculitis and fibrosing alveolitis in rheumatoid arthritis and their relationship to serum C1q binding activity and rheumatoid factor.

Two measurements of serum immune complexes, cryoglobulinaemia and 125I-C1q binding, have been performed in patients with severe rheumatoid arthritis (RA) and compared with normal levels. Cryoglobulinaemia was present in 20 out of 28 patients (71%) with extra-articular disease (mean level 17 micrograms/ml) including nodules, digital vasculitis, cutaneous ulcers, rash, neuropathy, lung disease and scleritis, but in none of 32 patients with joint disease alone (uncomplicated RA) (mean level 3 micrograms/ml). Cryoglobulinaemia correlates with, but probably does not antedate, extra-articular disease, and may be useful in predicting morbidity and mortailty in this group of patients. In contrast, serum 125I-Clq binding was raised in patients with uncomplicated RA and those with extra-articular disease, although levels were higher in the latter group. Both tests showed a negative correlation with serum haemolytic complement and a positive correlation with IgM rheumatoid factor although there were some sera with raised levels of rheumatoid factor without cryoglobulinaemia. These results suggest that cryoglobulinaemia is a better test than Clq-binding for demonstrating the presence of circulating immune complexes involved in the pathogenesis of extra-articular lesions.

Antigen-Antibody Complex↗

The clinical features and HLA associations of reactive arthritis associated with non-gonococcal urethritis.

Fifty-seven patients with arthritis associated with non-gonococcal genital infection have been studied. Synovitis characteristically affected one or a few joints, expecially the knee, ankle or metatarsophalangeal joints and was accompanied by tenosynovitis and enthesopathies--each in about one third of the patients. A quarter of the patients had ocular, cutaneous, or mucous membrane lesions (Reiter's syndrome). Although six patients developed a chronic or relapsing course, average duration of the acute episode in the majority was three to five months. Available evidence strongly suggests that infection following sexual intercourse, usually but not always with a new partner, was instrumental in the initiation of the disease. We have suggested the term 'sexually acquired reactive arthritis (SARA)' to emphasize the mode of acquisition of the disease, and note that similar syndromes are seen associated with gut infection. We consider that usage of the term Reiter's syndrome is correctly applied to only those cases which exhibited the characteristic triad of urethritis, arthritis and conjunctivitis with or without other cutaneous and mucous membrane lesions. Thirty-six of the 54 patients who were HLA typed (67 per cent) possessed the antigen HLA-B27. Of 30 who presented directly to a rheumatology unit 25 (82 per cent) were HLA-B27 positive. The other 24 patients initially attended a venereology clinic and only 11 (46 per cent) of these bore the antigen. This appears to reflect disease severity, HLA-B27 positive patients having a significantly longer duration of disease symptoms and a higher frequency of extra-articular manifestations, than those lacking this antigen.

Adolescent↗

Role of Chlamydia trachomatis and HLA-B27 in sexually acquired reactive arthritis.

Inflammatory arthritis, tendinitis, and fasciitis after non-specific urethritis ("sexually acquired reactive arthritis" (SARA)) was studied prospectively in 531 men with non-specific urethritis, with particular reference to the frequency of isolation of Chlamydia trachomatis and the presence of HLA-B27. Satisfactory cultures were obtained from the urethral swabs from 384 patients; and HLA typing was performed on 482, of whom 30 (6%) were HLA-B27-positive. Arthritis developed in 16 patients, and five of the 14 (36%) with satisfactory cultures were positive for C trachomatis; 135 of the patients without arthritis were also positive for C trachomatis, an identical proportion. Seven of the 15 patients (40%) with arthritis who were HLA-typed were HLA-B27-positive. Six of the 30 patients with HLA-B27 developed peripheral arthritis in contrast to only nine of the 452 patients lacking the antigen, suggesting a tenfold increase susceptibility. C trachomatis, however, was no more prevalent in cultures from HLA-B27-positive men than from the others. Thus carriage of C trachomatis is unlikely to be influenced by HLA-B27. C trachomatis may be an important pathogen in some cases of SARA but does not appear to be an exclusive trigger factor for this condition.

Arthritis↗

The clinical and pathogenetic significance of rheumatoid factors.

Rheumatoid factors are immunoglobulins with antibody specificity for antigenic sites on the Fc part of the heavy chain of IgG. The heterogeneity of RF in terms of antigenic specificity and class of immunoglobulin is indicative of the complexity of the provoking immune response. There is little doubt that in many patients rheumatoid factors are autoantibodies which form part of immune complexes, and that complexes containing IgG rheumatoid factor appear to be of pathogenetic importance. Although IgM rheumatoid factors are not specific for RA, their detection aids in the diagnosis and categorisation of rheumatoid arthritis. On the other hand, IgG rheumatoid factors occur in a variety of rheumatic diseases and are of little diagnostic value.

Adult↗

Rheumatoid and normal synovial tissue in longterm culture. Evidence of cell heterogeneity and an approach to quantitation of of populations and the effect of passage.

Longtern monolayer cultures of cells derived from explants of 21 normal and 31 rheumatoid synovial tissue specimens were studied and shown to be morphologically heterogeneous. The cultures were defined according to their cell size and their buoyant density as determined by separation on Ficoll density gradients. The investigations demonstrate that changes in these populations occurred with each passage of the cell lines. These findings emphasize the importance of using cultures of the same cultural age and passage for any comparative s tudy. The techniques described are useful for separating and defining the populations present in synovial tissue tissue cultures.

Arthritis, Rheumatoid↗

Respiratory involvement in systemic lupus erythematosus. A clinical and immunological study.

Thirty patients fulfilling conventional criteria for systemic lupus erythematosus and who presented with extensive pleural and pulmonary involvement were studied retrospectively. Four overlapping patterns of respiratory disease were identified and observations were made on their clinical presentation, radiographic abnormalities and response to treatment. A low incidence of severe renal disease was found in this series of patients and this was in keeping with the general finding of low serum binding using native DNA in a globulin Farr-binding technique (greater than 20% binding in only 4/21 (19%) of the series) and normal or elevated serum complement (C3) levels. Precipitating antibody detected by double diffusion and counter-current immunoelectrophoresis and probably reacting in most cases with single-stranded DNA was, however, detected in 66% of pretreatment serum samples tested. This evidence supports the idea that different types of anti-nuclear antibody may be associated with different clinical manifestations seen within a group of patients who broadly fulfil the criteria for SLE.

Adolescent↗

Human anti-DNA antibody: reference standards for diagnosis and management of systemic lupus erythematosus.

A technique for the measurement of DNA binding activity of sera is described which uses primary internal reference standards in a Farr assay. This allows the DNA binding activity of test sera to be measured in relation to the reference standards and the results are expressed as units/ml. The use of this standardized assay has led to diminished interassay variation and close interlaboratory correlation, and has provided a clinically useful test. In survey using the standardized assay, normal sera were found to have binding activity which did not exceed 15 units/ml; 71% of patients with systemic lupus erythematosus (SLE) had levels greater than 25 units/ml; while only 8% of patients with diseases other than SLE had levels above 25 units/ml. Values between 15 and 25 units/ml appeared to have little diagnostic significance.

Antibodies↗

Adverse reactions to Zn1-24 ACTH therapy associated with specific cellular immunity.

Lymphocyte transformation to 1-24ACTH, as assessed by the incorporation of tritiated thymidine, has been demonstrated to be associated with severe adverse reactions occurring in patients receiving a Zn-linked 1-24ACTH preparation (Tetra cosactrin depot, 'Synacthen'). Antibodies measured with an isotope-binding assay occurred commonly in all patients receiving therapy and did not correlate with adverse reactions. Lymphocyte transformation with the 1-24ACTH polypeptide, a part of the naturally occurring ACTH molecule, has not been previously recorded. The significance of antibodies and cell-mediated immunity to this polypeptide hormone is discussed.

Adrenocorticotropic Hormone↗