PubMed Health⌕ Search

Biomedical subjects

N D Hall

Publications and source records attributed to N D Hall.

At least 37 records · Page 2Linked to original sources
PubMed1992

Impaired suppressor cell activity due to surface sulphydryl oxidation in rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disorder with considerable evidence of impaired regulation of the immune response, including defective suppressor cell function, especially in the synovial membrane. We have investigated whether oxidation of cell surface thiols might be responsible for these defects and whether such cell function may be modulated towards normal by treatment with a sulphydryl-reactive drug, D-penicillamine. Using healthy mononuclear cells treated with an impermeant thiol blocker, induction of suppressor activity by incubation with the lectin Con A was not dependent on surface sulphydryl groups but suppressor activity was abolished by thiol blockade after Con A stimulation. Peripheral blood mononuclear cells from patients with active rheumatoid disease showed impaired Con A-induced suppressor activity which was enhanced to near-normal levels by incubating the rheumatoid cells with a sulphydryl reducing agent, 2-mercaptoethanol, or D-penicillamine. Con A-stimulation of cells from patients treated with intramuscular gold or D-penicillamine generated more active suppression than those from patients receiving non-steroidal drugs only. Mononuclear cells from patients with other chronic inflammatory joint diseases showed normal Con A-induced suppressor activity. These data support the conclusion that surface thiols on mononuclear cells in rheumatoid arthritis are reversibly oxidized by the disease process. This gives rise to aberrant cell function including impaired suppressor activity. Such a mechanism may be at least partly responsible for the defective immunoregulation seen in rheumatoid patients and thus be a relevant target for thiol containing antirheumatic drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness.

An impermeable thiol blocker has been used to investigate the role of sulphydryl (SH) groups in the production of and responsiveness to IL-2 by normal human T lymphocytes. Surface SH blockade of mononuclear cells prior to incubation with mitogen (phytohaemagglutinin, concanavalin A, CD3 MoAb) had no effect on production of IL-2 but markedly impaired cellular responsiveness to exogenous IL-2. Studies using MoAbs indicated that this effect was accompanied by decreased expression of both the CD25 and p75 subunits of the IL-2 receptor. Blocking surface SH groups did not affect binding of IL-2 to p75 on unstimulated mononuclear cells, but inhibited binding to high-affinity receptors on a T lymphoma cell line. The data are consistent with the hypothesis that sulphydryl groups on the IL-2 receptor are required for its function and may be involved in the interaction of the CD25 and p75 subunits leading to generation of the high-affinity binding site. The surface thiol identified on the IL-2 receptor may be a candidate for oxidation on cells from patients with chronic inflammatory diseases such as rheumatoid arthritis and thus contribute to the aberrant function of T cells in these patients.

Arthritis, Rheumatoid↗
PubMed1992

Autoantibodies to lipocortin-1 are associated with impaired glucocorticoid responsiveness in rheumatoid arthritis.

Autoantibodies to the antiinflammatory protein lipocortin-1 have been found in patients with rheumatoid arthritis (RA) receiving oral glucocorticoids. The highest antibody titers correlated with a requirement for high maintenance doses of steroid (> 7.5 mg/day prednisolone). Forty-two patients with RA were grouped according to high or low autoantibody titer. In 18 patients, peripheral blood leukocyte counts and phenotypic analysis were performed before and 4 h after a single intravenous (iv) dose of 100 mg hydrocortisone. The group with low titer antibody exhibited a normal poststeroid peripheral blood lymphopenia, but the response in the group with high antibody titer was considerably blunted. In a 2nd study, 24 patients received 3 separate doses of 1000 mg iv methylprednisolone. After 8 weeks the group with the high titer antibody had shown no improvements in clinical or laboratory variables observed in the group with low titer antibody. Thus, the presence of high titer antilipocortin-1 antibody is associated with impaired responses to glucocorticoid therapy both in terms of clinical efficacy and effects on the immune system. This could explain the relative glucocorticoid resistance reported in a proportion of patients with RA.

Aged↗
PubMed1991

Predictors of the long-term outcome of early synovitis: a 5-year follow-up study.

One hundred patients who presented to an Early Synovitis Clinic in 1979-81 were called for review after a minimum of 5 years. Sufficient data for analysis were obtained in 88 cases, of whom 36 had a final diagnosis of rheumatoid arthritis (19 seropositive, 17 seronegative) and 16 human parvovirus B19 arthropathy. Outcome was assessed by persistence of symptoms greater than 24 months and functional disability by Health Assessment Questionnaire. Sixty-two patients had persistent disease, with 26 showing some functional impairment (positive HAQ FDI). A number of presenting features were assessed for their ability to predict outcome at 5 years. Polyarticular onset of disease was associated with a poor prognosis but lacked both specificity and sensitivity. Certain laboratory tests at presentation, including positive rheumatoid factor and low serum sulphydryl levels, also indicated a poor outcome. Combining these serological abnormalities gave 100% specificity for detecting persistent, disabling disease but with rather low sensitivity. Thus, other test systems are required to increase further the successful prediction of clinical outcome in patients with early synovitis.

Adolescent↗
PubMed1990

Factor VIII related antigen in connective tissue disease patients and relatives.

This study assayed serum levels of FVIII Rag as a marker of endothelial injury in patients not only with frank connective tissue disease but also in those presenting with Raynaud's phenomenon and in families of those with systemic sclerosis. Elevated levels of FVIII Rag were found in 62% of patients with systemic sclerosis (SS), 38% with systemic lupus erythematosus (SLE), 67% with mixed connective tissue disease (MCTD) and in 17% with primary Raynaud's phenomenon. Twenty per cent of first degree relatives of patients with SS also demonstrated high levels of FVIII Rag and certain antibodies, namely those reacting with U1RNP and the centromere. The association between elevated FVIII Rag and antibodies linked to Raynaud's and vasculitis lends support to antibody involvement in pathogenesis. High levels of FVIII Rag in family members may reflect an increased susceptibility of endothelium to injury particularly since relatives also have a higher frequency of clinical features such as Raynaud's phenomenon.

Antibodies↗
PubMed1990

Radiological progression in rheumatoid arthritis: do D-penicillamine and hydroxychloroquine have different effects?

We studied 43 patients with active rheumatoid disease of less than 4 years' duration: 23 were given hydroxychloroquine and 20 penicillamine. Efficacy was assessed using clinical and laboratory variables. Radiological progression was measured using Larsen's method for scoring plain radiographs of the hands and feet. Twenty-four patients received 2 years' continuous therapy. Clinically both drugs were effective with falls in articular index and C-reactive protein. Initial radiological damage was less with penicillamine (P less than 0.05 by Wilcoxon rank sum test). By 2 years there were no significant differences between the two drugs; mean increases in Larsen score were 20.3 with penicillamine and 27.5 with hydroxychloroquine. Both groups progressed at a rate likely to give severe joint destruction over 10-20 years.

Arthritis, Rheumatoid↗
PubMed1989

Thymopentin (TP-5) in the treatment of rheumatoid arthritis.

A randomized control trial of TP-5 in rheumatoid arthritis is reported. In a multicentre study, 76 patients were treated with TP-5 50 mg or placebo three times a week for 3 weeks as a slow intravenous injection, and followed for 7 weeks. Clinical parameters such as the Ritchie index and sum score of swollen joints improved significantly on TP-5 compared to placebo. Laboratory parameters did not change but an increased skin test score to common recall antigens was observed. Toxicity was minimal. TP-5 is a potentially useful agent in the treatment of rheumatoid arthritis, although further studies are required to determine the optimal treatment regimen.

Arthritis, Rheumatoid↗
PubMed1989

HLA-DO-related restriction fragment length polymorphisms in rheumatoid arthritis: evidence for a link with disease expression.

Eighty-three patients with rheumatoid arthritis (RA) were investigated for HLA-DQ and DR locus restriction fragment length polymorphisms (RFLP). Of the 83 patients, 61 (73%) possessed the DR4 allele and within this group we have investigated the relative frequencies of two DQ beta gene variants of DQw3, DQw7 and DQw8, one of which we had previously found to be raised in Felty's syndrome. This analysis revealed a significantly higher frequency of DQw7 containing haplotypes in DR4 positive rheumatoid patients (64%) than in DR-matched healthy controls (42%). Furthermore, the distribution of DQw7 was biased towards those patients with greater disability indicated by the HAQ score, more systemic disease and higher titres of rheumatoid factor, suggesting that DQw7 may contribute to disease expression.

Arthritis, Rheumatoid↗
PubMed1989

Autoantibodies to recombinant lipocortin-1 in rheumatoid arthritis and systemic lupus erythematosus.

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kD protein, lipocortin-1. Autoantibodies to lipocortin-1 were measured by enzyme linked immunosorbent assay (ELISA) in 90 healthy subjects and in 63 patients with rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE), 26 with polymyalgia rheumatica, and 13 with chronic airways disease. Sixteen patients with RA receiving prolonged, high steroid doses (prednisolone greater than 7.5 mg/day) had raised IgM antilipocortin-1 levels, while 19 patients with RA untreated with steroids had normal levels. This association was independent of disease activity. In SLE, raised antilipocortin-1 levels were associated with active disease and were independent of steroid treatment. Antilipocortin-1 antibody levels were not raised in patients with polymyalgia rheumatica and chronic airways disease. Thus steroid treatment alone appears insufficient to induce antilipocortin-1 antibodies, unless an underlying autoimmune state is also present. In RA, antilipocortin-1 antibodies may impair anti-inflammatory actions of steroids and render some patients 'steroid resistant'.

Aged↗
PubMed1987

The generation of lipid peroxides by stimulated human neutrophils. Detection using phenol red oxidation.

When activated, phagocytic cells undergo a burst of oxidative metabolism, consuming oxygen and converting it to several products including superoxide anion and hydrogen peroxide. The latter may be quantified using an assay based on the oxidation of phenol red catalysed by horseradish peroxidase. This method has been employed to evaluate peroxide formation by human neutrophils activated in vitro with a variety of stimuli. Evidence is presented to show that neutrophils secrete different major peroxides depending upon the stimulus, its concentration and the incubation time. Based on inhibition studies using enzymes and drugs these may be identified as hydrogen peroxide and a lipoxygenase product, probably 5-hydroperoxyeicosatetraenoic acid (5-HPETE). Thus, phenol red oxidation may, under certain circumstances, represent a simple assay of lipoxygenase activity in stimulated human neutrophils.

Arachidonic Acids↗
PubMed1987

Enhanced oxidative metabolism of neutrophils from patients with systemic sclerosis.

Pathological features of systemic sclerosis (SS) such as endothelial cell injury may be associated with damage caused by active oxygen species, especially peroxides. Neutrophils from SS patients express more Fc(IgG) receptors and generate significantly more peroxide than control cells when cultured alone or with heat-aggregated IgG, but not with F-Met-Leu-Phe. We suggest that circulating neutrophils are activated in SS and may, through secretion of toxic peroxides, contribute to the early vascular pathology of this disease.

Female↗
PubMed1986

Clinical and laboratory effects of nifedipine in Raynaud's phenomenon.

The calcium channel blocking drug nifedipine was shown to be more effective than placebo as a treatment for Raynaud's phenomenon. Given in a dose of 10 mg four times a day it was well tolerated and reduced both the frequency and the severity of vasospastic attacks. There was, however, a large individual variation in response and while approximately half the patients showed marked improvement others showed no improvement at all. Patients with idiopathic Raynaud's phenomenon responded more favourably than those with systemic sclerosis. Nifedipine was shown to inhibit mitogen-induced lymphocyte proliferation but only in patients who responded to the drug clinically. Calcium channel blocking drugs may therefore have potential as immunoregulatory agents.

Adolescent↗