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N C Wood

Publications and source records attributed to N C Wood.

14 recordsLinked to original sources
PubMed1992

In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid arthritis.

Interleukin 1 (IL-1) has been implicated as an inflammatory mediator in rheumatoid arthritis (RA). Many cell types, including macrophages, lymphocytes, fibroblasts, and endothelial cells, can produce IL-1 and it is known that IL-1 production is under transcriptional control. It has, however, been difficult to define in vivo the predominant cellular source of this mediator in RA. Here, we have used the combination of in situ hybridization of mRNA and cellular immunophenotyping with monoclonal antibodies to show that the IL-1 beta gene is expressed predominantly by CD14-positive macrophages in synovial tissue from patients with RA. Synovial macrophages were also associated with the immunoreactive IL-1 peptide. These cells appear to be the major source of IL-1 beta within the rheumatoid synovium in vivo and must be regarded as playing a central role in the chronic inflammation and joint destruction of RA.

Antigens, CD↗
PubMed1992

In situ hybridization of IL-6 in rheumatoid arthritis.

IL-6, an important mediator of the acute phase response, has been implicated in the pathogenesis of rheumatoid arthritis (RA). Many cell types including macrophages, T cells, B cells, endothelial cells and fibroblasts can produce this cytokine and production is largely regulated at the level of gene transcription or mRNA stabilization. In this paper we have first measured the levels of IL-6 activity in synovial fluid (SF) and serum from patients with RA and then localized IL-6-producing cells in the synovium by in situ hybridization combined with immunophenotyping. Patients with RA had raised levels of IL-6 in both SF and serum compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients tested serially after admission to hospital, serum IL-6 was initially raised and, unexpectedly, increased with clinical improvement. In situ hybridization of IL-6 mRNA showed positive cells both in the lymphocyte-rich aggregates and adjacent to small blood vessels. With immunophenotyping it was found that cells containing IL-6 mRNA were often in contact with CD14+ tissue macrophages and double immunophenotyping revealed that immunoreactive IL-6 was often associated with synovial T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Soluble CD4 in patients with rheumatoid arthritis and osteoarthritis.

An ELISA was used to measure the soluble form of the leukocyte surface antigen CD4 (sCD4) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD4 in both their sera and synovial fluid compared to age-matched healthy controls. In patients with osteoarthritis levels of sCD4 in SF and sera were lower than in RA but higher than in sera of healthy individuals. Mononuclear cells from the synovial fluid of RA patients were found to produce spontaneously high levels of sCD4, but autologous blood cells only produced comparable levels after in vitro stimulation with mitogenic lectin. In individual RA patients with active disease, serial sCD4 levels fell preceding clinical improvement. In three patients where serum sCD4 levels fell and clinical improvement occurred, subsequent small increases in serum sCD4 preceded increased clinical disease activity by up to 5 days. Synovial fluid levels of sCD4 correlated positively with soluble interleukin 2 receptor levels but no correlation was found with sCD8 levels. We conclude that the release of sCD4 reflects the involvement of T helper cells and macrophages in the pathogenesis of joint inflammation, especially in RA.

Adult↗
PubMed1991

Plasma levels of interleukin-1-alpha in rheumatoid arthritis.

Interleukin-1-beta (IL-1 beta) has been implicated as an inflammatory mediator in rheumatoid arthritis (RA) but little is known about the related cytokine, IL-1 alpha, in this disease. IL-1 alpha has biological properties similar to IL-1 beta but, unlike IL-1 beta, remains mostly cell-associated. In this study plasma IL-1 alpha was measured by radioimmunoassay in patients with RA and in healthy controls. Plasma levels were compared with conventional measures of disease activity. The mean levels in the two groups were not significantly different and, within the patient group (n = 53), the only significant cross-sectional correlation was between plasma IL-1 alpha and ESR. In longitudinal studies, some individual patients had plasma IL-1 alpha levels that correlated with different measures of disease activity. We conclude that while IL-1 alpha may be involved in the immunopathogenesis of RA, its measurement in plasma seems to offer little of clinical value.

Adult↗
PubMed1990

Soluble CD8 in patients with rheumatic diseases.

An ELISA was used to measure soluble CD8 (sCD8) in the sera and synovial fluids (SF) of patients with rheumatic diseases. Patients with rheumatoid arthritis (RA) had raised levels of sCD8 both in their sera and in their SF compared with patients with osteoarthritis and age-matched healthy controls. In individual RA patients, serial serum sCD8 levels initially fell and then rose preceding clinical improvement. In four patients where serum sCD8 levels rose and clinical improvement occurred, subsequent spontaneous decreases of serum sCD8 level preceded increased clinical disease activity by up to 2 weeks. In general, RA SF mononuclear cells (SFMNC) spontaneously produced high levels of sCD8. In contrast, autologous peripheral blood MNC only produced comparable levels after mitogenic stimulation. Incubation of SFMNC with increasing concentrations of human recombinant tumour necrosis factor alpha resulted in a dose-dependent potentiation of sCD8 release into the supernatant. There was an inverse relationship between the ability of SFMNC to release sCD8 and soluble interleukin-2 receptor, indicating that the CD8+ T cell population may play an important immunoregulatory role in RA.

Adult↗
PubMed1990

In situ hybridisation.

In situ hybridisation of mRNA in tissues or cell preparations is a powerful technique for studying gene expression. When combined with cell phenotyping with monoclonal antibodies it gives insights into the cellular basis of disease in vivo. The technique has also been used widely to identify foreign nucleic acids--for example, bacterial or viral, in host cells. The major disadvantages of this approach in the past have been that it was technically demanding, time consuming, and provided qualitative rather than quantitative results. Now, with the use of non-radioactive probes and improved imaging systems, the full potential of this form of molecular analysis is increasingly accessible and should generate rapid advances in many fields.

Arthritis, Rheumatoid↗
PubMed1989

Interleukin 1 in rheumatoid arthritis: potentiation of immune responses within the joint.

Specific immunoassays were used to measure IL-1 peptides in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and in the serum of age-matched healthy controls. Patients with RA had raised levels of both IL-1 beta and IL-1 alpha in their sera compared to controls. Synovial fluid levels of IL-1 beta significantly correlated with immunoreactive IL-2 and soluble IL-2 receptor (sIL-2R). In addition, incubation of synovial fluid MNC with human recombinant (hr) IL-1 caused a dose-dependent increase in the level of sIL-2R in the cell supernatant. Finally, production of IL-1 beta and IL-6 from RA peripheral blood (PB) and synovial fluid (SF) MNC was examined. PBMNC spontaneously produced low levels of IL-1 beta and IL-6 that were augmented by the addition of hr IL-1 alpha. In contrast, SFMNC spontaneously produced high levels of IL-1 beta but only low levels of IL-6, again this production was augmented by the addition of hr IL-1 alpha. Taken together, the data suggests that IL-1 potentiates immune responses within the joint.

Arthritis, Rheumatoid↗
PubMed1988

Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition.

An ELISA was used to measure soluble IL-2R (sIL-2R) in the sera and synovial fluids of patients with rheumatic diseases. Patients with rheumatoid arthritis had raised levels of sIL-2R both in their sera and in their synovial fluid compared to patients with osteoarthritis and age-matched healthy controls. Mononuclear cells from the synovial fluid of rheumatoid arthritis patients were found to produce spontaneously high levels of sIL-2R which eluted at approximately m.w. 40,000 on gel filtration. In contrast, autologous peripheral blood cells only produced comparable levels upon stimulation with mitogenic lectin. Sequential studies indicated that serum sIL-2R levels were highly correlated with disease activity, indicating that measurement of sIL-2R may be a useful clinical marker in the future. Within the joint, synovial fluid sIL-2R levels correlated significantly with immunoreactive IL-1 beta levels, providing evidence for a role of IL-1 in immune activation in the synovium. In synovial fluids, sIL-2R level also correlated with functional inhibition of IL-2-driven responses in vitro. Furthermore, sIL-2R immunoreactivity in synovial fluid eluted at m.w. 100,000 coeluting with IL-2-inhibitory activity and consistent with a role for sIL-2R in down-regulation of IL-2 responses. The abnormal m.w. may be accounted for by complex formation in the synovial fluid. Given the ability of sIL-2R to bind IL-2, the presence of sIL-2R within the joint may contribute to the well documented "IL-2 defect" seen in rheumatoid arthritis.

Adult↗
PubMed1988

Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis.

The mean plasma level of interleukin 1 beta (IL-1 beta), measured by immunoassay, was significantly higher in 51 patients with rheumatoid arthritis (RA) than in 21 healthy controls of similar age. Further, in the RA group, plasma IL-1 beta correlated positively with Ritchie joint index, pain score, and erythrocyte sedimentation rate and correlated negatively with haemoglobin concentration. In individual patients with active disease who had serial measurements, plasma IL-1 beta also correlated with clinical disease activity. These results support the idea that IL-1 beta has a central role in the pathogenesis of RA.

Adult↗
PubMed1988

Serum interleukin-2-receptor in rheumatoid arthritis: a prognostic indicator of disease activity?

Interleukin-2 (IL-2) is an important growth factor for T lymphocytes. Its effects are mediated by cell surface receptors (IL-2 R) expressed on activated T cells. Receptor protein can be shed from cell membranes and the soluble form (sIL-2 R) is detectable by enzyme linked immunosorbent assay (ELISA). We have studied serial levels of sIL-2 R in the sera of patients with rheumatoid arthritis (RA). In 13 patients with active disease, the mean serum level of sIL-2 R was raised compared to age-matched healthy controls. In 48 samples taken at different times from 13 patients, serum sIL-2 R correlated significantly with Ritchie joint index, duration of early morning stiffness, patient pain score, physician's assessment, erythrocyte sedimentation rate (ESR) and platelet count. In individual patients, serial sIL-2 R serum levels fell with treatment preceding clinical improvement. In four patients where serum sIL-2 R levels fell and clinical improvement occurred, subsequent spontaneous increases of serum sIL-2 R level preceded increased clinical disease activity by up to 2 weeks. Serum sIL-2 R level in RA probably reflects activation of underlying immunopathogenic mechanisms and appears to be an excellent monitor of clinical disease activity. More importantly, a rising level may also predict exacerbation of disease activity.

Adult↗
PubMed1987

Abnormal intestinal permeability. An aetiological factor in chronic psychiatric disorders?

Abnormal intestinal absorption has been suggested as an aetiological factor in schizophrenia. A procedure for investigating intestinal permeability was carried out in a group of chronic psychiatric in-patients. A proportion of the subjects studied showed abnormal intestinal permeability which could not be attributed to established bowel disease. Patients who were receiving neuroleptic but not anticholinergic drugs were those most often showing abnormal intestinal permeability. This work is at an early stage of development but preliminary findings suggest that further investigations should be carried out to establish the circumstances in which changes in intestinal permeability may be associated with mental illness.

Celiac Disease↗
PubMed1986

Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrato bismuthate (TDB) tablets or cimetidine.

Eighty patients with duodenal ulcer were randomly allocated to treatment with tripotassium dicitrato bismuthate (TDB) tablets or cimetidine. Ulcers healed in 78% of patients treated with TDB and in 74% treated with cimetidine, supporting previous observations that the efficacy of these two agents is similar. Duodenal ulcer recurred in 43% of patients in the 12 months after treatment with TDB and in 78% of patients treated with cimetidine, with a significantly greater incidence of recurrence 6-12 months after cimetidine treatment. Tripotassium dicitrato bismuthate tablets may be preferable to cimetidine in the initial management of duodenal ulcer, because they offer a smaller likelihood of recurrence in the 12 months after successful treatment.

Adult↗
PubMed1985

Inhibitory effects of chlorpromazine on Candida species.

Chlorpromazine was tested for antifungal activity by using Candida albicans and standard assays. The MIC of chlorpromazine was 35 micrograms/ml; the minimal fungicidal concentration was also 35 micrograms/ml. The minimal effective concentration was 2.2 to 3.5 micrograms/ml (using assays based on quantitative cultures and growth). There was a slight positive interaction between chlorpromazine and amphotericin B but no interaction between chlorpromazine and rifampin. Chlorpromazine also inhibited C. krusei, C. parapsilosis, C. tropicalis, and Torulopsis glabrata. We conclude that phenothiazines have direct anti-Candida activity and that these drugs appear to have a broad antimicrobial spectrum.

Amphotericin B↗