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Biomedical subjects

P Shepherd

Publications and source records attributed to P Shepherd.

43 records · Page 3Linked to original sources

Changes in immune function in patients with rheumatoid arthritis following treatment with sodium aurothiomalate.

The mitogenic response of peripheral blood lymphocytes from 21 patients with rheumatoid arthritis to concanavalin-A (con--A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM) was significantly lower than in 30 normal subjects. After 15--24 weeks' treatment with sodium aurothiomalate (GST) the response to these mitogens rose to within the normal range. Improvement over pretreatment values was significant for con-A and PWM measured as area under the dose response curve but only for con--A if response at optimal mitogen concentration is the sole criterion. The improvement in PHA response was not significant with either method of measurement. There was an improvement in disease activity by 15--24 weeks as measured by a fall in serum C-reactive protein (CRP), IgM rheumatoid factor (RF), Clq binding activity (ClqBA), and Ritchie articular index. Con--A lymphocyte responsiveness was inversely related to serum CRP levels, but measurements of disease activity were otherwise unrelated to lymphocyte mitogen responsiveness. The observed improvement in peripheral blood lymphocyte responsiveness during gold treatment contrasts with the suppressive effect of gold in vitro. We suggest that the improvement in lymphocyte function is due to the lessening of rheumatoid disease activity during gold treatment, and that the low serum gold levels in our patients were insufficient to mask this effect. Sera from some of our patients were capable of suppressing the function of normal lymphocytes, and this was less apparent after treatment. The suppressive effect of sera correlated with ClqBA. Suppressive factors in serum, including possibly immune complexes, may be one factor leading to suppression of lymphocyte function during rheumatoid arthritis. Such an inverse relationship between humoral and cellular immune mechanisms might influence the clinical expression of rheumatoid arthritis.

Arthritis, Rheumatoid↗

Fall in immune complex levels during gold treatment of rheumatoid arthritis.

Prior to starting gold treatment 30 patients with rheumatoid arthritis had an elevated mean level of circulating immune complexes measured by Clq binding activity. Gold treatment led to an improvement in disease reflected by significant falls in erythrocyte sedimentation rate (p less than 0.001), C-reactive protein (p less than 0.01), Ritchie articular index (p less than 0.001), and duration of morning stiffness (p less than 0.05). Concurrently immune complex levels fell, and this change first reached significance after 3 months' treatment (p less than 0.05). Serum Clq binding activity was not related to clinical and laboratory measurements of joint inflammation. This suggested to us that there is no direct immunopathological relationship between circulating immune complexes and joint inflammation in rheumatoid arthritis. Serum Clq binding activity was strongly related to IgM-RF levels measured at latex titre (r - 0.7, p less than 0.001). Removal of immune complexes from serum with Sepharose 4B-staph A (staphylococcal protein A) led to a fall in IgM-RF from 2 mg/ml (2 g/l) to 0.4 mg/ml (0.4 g/l). This suggests that the reason for the relationship between Clq BA and IgM-RF is that, on average 80% of serum IgM-RF exists as part of immune complexes containing IgG.

Adult↗

Platelet-aggregating immune complexes and intraplatelet serotonin in idiopathic glomerulonephritis and systemic lupus.

Immune complex-like material was studied using the platelet-aggregation test (PAT) in 114 patients with idiopathic glomerulonephritis and 55 patients with SLE nephritis, and the results obtained compared with Raji cell and Clq-binding assays. The platelet-aggregating material was not thrombin, and eluted from Sepharose CL/6B columns with a molecular weight of greater than 500,000 daltons. Sera from 17 of 55 patients with SLE nephritis were positive in all three assays, 50/55 in at least one assay. No circulating material was detected by the Raji cell assay in idiopathic glomerulonephritis patients, but both the Clq-binding and PAT assays detected material in patients with acute post-infectious nephritis and mesangiocapillary glomerulonephritis. Patients with membranous nephropathy and Henoch-Schönlein purpura were positive in the PAT, although generally negative in the other assays of immune complexes. The amount of platelet-aggregating material (PAM) found in the sera of patients with both idiopathic glomerulonephritis and SLE nephritis correlated closely with the depletion of intraplatelet serotonin, suggesting that this material is a major mechanism of in vivo platelet activation in these patients.

Antigen-Antibody Complex↗

Platelet-aggregating immune complexes in idiopathic glomerulonephritis and SLE.

Immune complex-like material with a molecular weight of greater than 500,000 Daltons was detected in the majority of sera from patients with idiopathic glomerulonephritis, as well as in systemic lupus. In the Raji cell and Clq binding assays the glomerulonephritis sera gave, in general, negative results. Patients with membranous nephropathy, minimal change disease and Henoch-Schönlein purpura also gave positive results in the platelet test, in agreement with other tests not dependent upon complement fixation by the complexes. The amount of platelet-aggregating material detected in vitro correlated closely with in vivo depletion of intraplatelet amines, judged by serotonin concentrations; which suggests that this material may play a major role in platelet activation within the circulation.

Antigen-Antibody Complex↗

Two methods for producing peripheral anosmia in dogs.

Two methods for producing peripheral anosmia in the dog were described. One method involved infusion of 3.5% zinc sulfate into the nasal cavity. An anosmia lasting at least 6 weeks, and, in most cases, for several months, was produced. A second technique, producing short periods of reversible anosmia, was the insertion of a tracheostomy tube with inflatable cuff. Inflation of the cuff prevented the dogs from inhaling air over the olfactory mucosa. Deflation of the cuff restored functional olfaction. The advantages and disadvantages of each technique were discussed.

Animals↗