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N D Hall

Publications and source records attributed to N D Hall.

66 records · Page 4Linked to original sources

The nonspecific inhibitory effect of synovial tissue extracts on leucocyte migration in vitro.

The leucocyte migration inhibition test (LMT) has been used to search for specific antigens in rheumatoid synovial tissue. Synovial samples were collected from 20 patients with rheumatoid arthritis, from 1 patient with ankylosing spondylitis, and from 1 patient with pigmented villonodular synovitis. Inhibitory material was obtained from all 21 synovia with inflammatory disease but not from the noninflammatory synovium. The tissue extracts generally caused nonspecific migration inhibition when tested against a total of 157 pairs of rheumatoid and control leucocytes. However, occasional samples did induce migration inhibition restricted to either rheumatoid or control cells. The inhibitory factor was shown to be membrane associated and of high molecular weight (greater than 10(6) daltons). The results of this extensive study do not support the conclusions drawn from earlier reports based on smaller numbers of experiments. No evidence was obtained for the existence of specific antigenic material associated with the synovial membrane in rheumatoid arthritis.

Adult↗

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. I. An increased subpopulation of cells in rheumatoid arthritis detected with Facb rosettes.

The chronic production of IgM and IgG antiglobulins is a major feature of rheumatoid arthritis. This implies an abnormal interaction between rheumatoid leucocytes and IgG. A novel rosette assay employing rabbit Facb-coated calf red blood cells has been developed to study receptors for IgG on peripheral blood lymphocytes. Cells were obtained from groups of patients with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and healthy control subjects. Receptors for Facb were found on an increased proportion of lymphocytes from RA patients compared with the other groups tested. It has been shown that the Facb rosette assay detects a subpopulation of lymphocytes bearing receptors for the Fc region of IgG. This receptor is clearly capable of recognising and binding only the C gamma 2 domain within the Fc region. As such it shows different specificity from some other Fc receptors detected on mononuclear cells. The number of Facb rosette-forming lymphocytes in an individual sample correlated well with the number of cells bearing 'high avidity' Fc receptors. However, the incidence of these cells in RA patients could not be correlated with disease activity, disease duration, or levels of IgM and IgG rheumatoid factor. Thus increased Facb rosette cells may represent a fundamental imbalance of the immune response in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗

A combined clinical and immunological assessment of four cyclophosphamide regimes in rheumatoid arthritis.

Four dosage regimes of cyclophosphamide have been compared in patients with late rheumatoid arthritis, in an attempt to separate toxicity from efficacy. Joint inflammation was assessed clinically and objectively by quantitative thermography. Delayed hypersensitivity in vitro was assessed using leucocyte migration inhibition (L.M.T.) to a standard antigen, Streptokinase. There was no significant difference in clinical response or side-effects between a continuous oral regime (1 mg/kg/day) and the same total dose given as an intermittent oral regime. Responders and non-responders were seen in both groups and there was a significant relationship between clinical response and fall in platelet count, suggesting a variable threshold. The same total dose given as an intermittent intravenous regime caused considerable side-effects but these could be avoided by the addition of methylprednisolone. Both intravenous regimes induced a much more rapid fall in the Thermographic Index (T.I.) than the oral regimes. Indeed many patients receiving oral cyclophosphamide showed an increase in joint inflammation in the first three weeks of treatment. Immunological studies demonstrated a corresponding increase in reactivity to Streptokinase over this period. There was a highly significant correlation between changes in L.M.T. and T.I. both early in treatment and, in the oral groups, over a period of six months.

Administration, Oral↗

Characterization of macrophage cytotoxicity factor (MCF).

Allogenetically sensitized T lymphocytes secrete in the presence of the specific antigen a factor which renders macrophages cytotoxic to target cells in vitro, macrophage cytotoxicity factor. Cytotoxicity is expressed as 51Cr release from labeled target cells. Experiments are described to characterize chemically nonspecific MCF activity. After purification on a DEAE-cellulose column, active material elutes from Sephadex G-100 in a single peak. Assaying individual fractions of this peak shows that nonspecific MCF activity is found at a mol. wt. of 28,000+/-5,000. This material is stable at -70 degrees C several months.

Animals↗

Circulating activated lymphocytes in rheumatoid arthritis: a marker of synovial inflammation.

Peripheral blood lymphocytes have been studied in rheumatoid arthritis using a Ficoll density gradient in which activated cells separate as low density lymphocytes (LDL). Increased numbers of LDL are found in rheumatoid patients with active synovitis but not in those with active extraarticular disease such as vasculitis in the absence of active synovitis. The association of activated cells with synovitis is confirmed by serial studies during cyclophosphamide therapy in which LDL correlate with a computerized thermographic index of joint inflammation. The separate immunological markers of vasculitis and synovitis, and the possible role of LDL in the pathogenesis of the latter, are discussed.

Arthritis, Rheumatoid↗

Serum sulphydryl levels in early synovitis.

The determination of serum sulphydryl levels has been assessed as a diagnostic/prognostic indicator of rheumatoid arthritis in patients attending an early synovitis clinic. This simple assay has been compared with other test systems including C-reactive protein, plasma viscosity, IgM rheumatoid factor and immune complexes. Results show that a low serum sulphydryl at presentation is a useful prognostic indicator for development of persistent synovitis. Patients with normal sulphydryl levels suffered only mild or transient symptoms. These results suggest that, since stimulated phagocytes generate the oxygen-derived species responsible for sulphydryl oxidation, such cells are active before the patient develops persistent symptoms.

Arthritis, Rheumatoid↗

Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders.

OBJECTIVE: It is well established that connective tissue diseases such as systemic lupus erythematosus (SLE) are associated with a weak or absent acute phase response, although elevated serum interleukin 6 levels have been described. In this study, we have sought to correlate serum levels of IL-6 with standard laboratory and clinical assessments of disease activity in two connective tissue diseases, namely SLE and systemic sclerosis (SSc), and, for comparative purposes, rheumatoid arthritis (RA). METHODS: Serum IL-6 levels were determined by bioassay and also, in some sera, by immunoradiometric assay. They were compared with two inflammatory parameters, serum C-reactive protein (CRP) and plasma viscosity (PV), and with appropriate clinical measurements in the various patient groups, including BILAG in SLE, the skin score in SSc, and the Ritchie index in RA. RESULTS: Serum IL-6 (SeIL-6) levels were elevated in active SLE, SSc, and RA. This was poorly correlated with the acute phase response in SLE and SSc, but there was a strong relationship of SeIL-6 to disease activity in these conditions. In SLE, the BILAG disease activity index correlated best with SeIL-6 levels while there was only a weak relationship between CRP and IL-6, and no relationship between CRP and disease activity. In SSc there was a relationship of disease activity to SeIL-6 but not between SeIL-6 and either CRP or PV. In a small RA group there was a much stronger relationship of SeIL-6 to CRP and PV, as has been previously described. CONCLUSION: The determination of SeIL-6 may be a useful indicator of disease activity in those patients groups, including SLE and SSc, in which a normal acute phase response by the liver is often lacking. The mechanism underlying this hepatic impairment requires further investigation, but is clearly not due to a failure to generate the appropriate cytokine signal. Excessive local or systemic production of IL-6 in connective tissue diseases could play an important pathogenic role in these conditions, for example through stimulating autoantibody synthesis.

Arthritis, Rheumatoid↗