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Biomedical subjects

G Kingsley

Publications and source records attributed to G Kingsley.

At least 19 recordsLinked to original sources
PubMed1996

A comparison of conflict tactics in the supervisory process.

This study investigated three different tactics clinical supervisors in communication disorders predicted they would use in a specific conflict situation. One hundred-sixty supervisors were asked to read one of three case scenarios describing a conflict situation within the supervisory process. All scenarios depicted a student-clinician who had not completed a reading assignment requested by the supervisor. The scenarios differed only in the supervisee's response to the supervisor's question about the incomplete assignment. Subjects were asked to indicate how likely they might be to use each of 15 comments that reflected categories of conflict tactics: avoidance, competitive, or collaborative tactics. Supervisors' choice of tactics differed depending on the response of the supervisee. Overall, supervisors most often chose collaborative responses, followed by avoidance responses and (least often) competitive responses. Implications are discussed in terms of impact on the supervisory process in communication disorders.

Communication↗
PubMed1995

How do second-line agents work?

The pathogenesis of rheumatoid arthritis remains unknown. Disease modifying anti-rheumatic drugs are commonly used to treat rheumatoid arthritis patients. Their use in rheumatoid arthritis was discovered serendipitously and their modes of action remain unknown. This article reviews current hypotheses on the mechanisms of action of established DMARDs. Most of them have anti-inflammatory properties and some are immunomodulators. We also discuss a number of novel agents which are potential new DMARDs.

Antirheumatic Agents↗
PubMed1995

Peripheral blood and synovial fluid monocyte expression of interleukin 1 alpha and 1 beta during active rheumatoid arthritis.

OBJECTIVE: To investigate the mononuclear cell (MNC) types from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) expressing interleukin-1 beta and -1 alpha (IL-1 beta, IL-1 alpha). METHODS: PB and SF MNC from 16 patients with classical or definite RA and controls were analyzed by flow cytometry for IL-1 beta and IL-1 alpha staining. RESULTS: MNC from normal individuals do not stain for either IL-1 beta or IL-1 alpha. By contrast, PB and SF CD14+ monocytes from patients with active RA show significant staining for surface and intracellular IL-1 beta and IL-1 alpha. Furthermore, the erythrocyte sedimentation rate (ESR) correlates with the surface expression of IL-1 alpha (r = 0.52, p < 0.05) while the number of active joints (i.e., tender and/or swollen) correlate with the intracellular expression of IL-1 beta (r = 0.58, p < 0.03) in CD14+ monocytes. CONCLUSION: The analysis of IL-1 beta and IL-1 alpha expression on CD14+ monocytes from peripheral blood by flow cytometry could be a potential immunological marker of disease activity in RA and its variation could be used to monitor the effects of therapy.

Antigens, CD↗
PubMed1994

Monoclonal antibody therapy in rheumatic disease.

In rheumatic disease, monoclonal antibodies have been used for the treatment of refractory rheumatoid arthritis, systemic lupus erythematosus, unresponsive vasculitis and relapsing polychondritis. Our greatest experience has however been with rheumatoid arthritis. After molecular engineering, hybrid monoclonal antibodies constructed from animal sources become largely human, and thus well tolerated, and highly specific. They can be focused selectively to particular targets, but the problem is to identify the causative antibody. In rheumatoid arthritis, we do know a great deal about the pathogenesis of the disease and rational targets can be selected. The major histocompatibility complex class II molecules would theoretically be the most effective target, but no specific antigen has been identified. Total blockade of all class II molecules would probably result in unacceptable immunosuppression. Despite this handicap, anti-HLA-DR4 monoclonal antibodies have been used in humans in an attempt to generate an anti-idiotypic response against DR4. T lymphocytes are known to play a major role in the pathogenesis of rheumatoid arthritis, thus targeting their surface markers would be a reasonable approach to monoclonal antibody therapy. Trials have been conducted using antibodies against the surface markers CD7, CD5, CDw52 and CD4. Further work has centered on differentiation antigens. Preliminary evidence suggests anti-interleukin-2-receptor monoclonal antibodies may be effective in rheumatoid arthritis. There have also been reports of attempts at anti-cytokine immunotherapy. Adhesion molecules would be another potential target. The ongoing trials have given us much insight into the pathogenesis of rheumatoid diseases and led us to the stage where we are now attempting to identify appropriate therapeutic regimes and combinations to maximise patient benefit. At present, we must continue our research for the causative antigen.

Antibodies, Monoclonal↗
PubMed1994

Adhesion molecules in rheumatoid arthritis: role in the pathogenesis and prospects for therapy.

The essential role played by cell adhesion and migration in the generation of chronic synovitis is now beyond doubt. Some of the beneficial effects of currently used drugs may be related to their ability to interfere with these mechanisms. The complexity of the process, however, means that there are many potential targets for therapeutic intervention and therefore further studies of the basic mechanisms are necessary to identify those which are most important.

Arthritis, Rheumatoid↗
PubMed1993

Current perspectives in reactive arthritis.

Reactive arthritis (ReA) is an inflammatory arthritis triggered by infection, usually urethritis or gastroenteritis, and is strongly associated with the MHC class I antigen HLA-B27. Two recent observations have excited interest: first, antigen and DNA from the triggering bacteria have been identified in the joint and, second, ReA synovial T cells have been found to respond specifically to the bacterium that caused the initiating infection. Because the trigger of ReA, its onset and the MHC association are all clearly defined, we can investigate hypotheses that are impossible to study in other forms of human arthritis. Here, Gabrielle Kingsley and Jochen Sieper review the topic in the light of a recent workshop.

Animals↗
PubMed1993

Excessive and dysregulated secretion of prolactin in rheumatoid arthritis: immunopathogenetic and therapeutic implications.

Prolactin (PL) is essential for the normal function of the immune system. It is required for the induction of a number of autoimmune conditions in experimental animals. The role of prolactin in the immunopathogenesis of autoimmune human disease has not been established. RA is characterized by a variety of immune and inflammatory processes which determine disease activity. It has a pronounced diurnal periodicity with a peak at 03.15 hours. Since PL has a diurnal rhythm of secretion in man with a peak at about 02.00 hours, it may contribute to the nocturnal worsening of RA. We show that patients with RA secrete an excess of prolactin as evidenced by an upregulated diurnal periodicity and an abnormal increase in plasma prolactin concentration following surgery. By contrast, patients with chronic osteomyelitis, who had chronic inflammation of similar severity to patients with RA, had a normal prolactin diurnal rhythm and response to surgery. Hence, the abnormal changes in prolactin physiology seen in RA appear to be a feature of the disease per se rather than related to chronic inflammation. The elevated levels of prolactin may contribute to disease activity by augmenting immune processes and may be an additional genetic factor, independent of HLA-DR4, in the immunopathogenesis of RA. Furthermore, the effective inhibition of prolactin secretion and/or action may have potential as therapy for RA.

Adult↗
PubMed1993

T cells are responsible for the enhanced synovial cellular immune response to triggering antigen in reactive arthritis.

In reactive arthritis (ReA) there is specific proliferation of synovial fluid (SF) mononuclear cells (MNC) to the triggering bacterial antigen; comparatively little or no response is seen in peripheral blood (PB). To investigate the mechanism of this elevated local immune response, we examined patients with typical ReA who showed an enhanced antigen-specific synovial immune response in bulk culture. Using separated fractions of T cells and antigen-presenting cells (APC) from PB and SF we showed that the synovial T cells rather than SF APC are responsible for the specific proliferation. By limiting dilution analysis, the frequency of T cells responding to the specific antigen was found to be significantly increased compared with the frequency of irrelevant antigen-specific T cells. Furthermore, the frequency of T cells responding to the specific antigen was higher in SF (between 1/619 and 1/4846, mean 1/2389) than in PB (between 1/1286 and 1/16,279, mean 1/7350). We conclude that the specific synovial cellular immune response in ReA is mainly due to an expansion of antigen-specific T cells within the joint. However, the non-specific hyper-reactivity of SF T cells and differences between SF and PB APC may make a more minor contribution.

Adult↗
PubMed1993

The immunopathogenesis and immunotherapy of autoimmune disease.

A conference entitled 'The Immunopathogenesis and Immunotherapy of Autoimmune Disease' was held at the Royal College of Physicians on 20 May 1992. Its aim was to consider advances in pathogenesis and their translation into therapeutic targets.

Autoimmune Diseases↗
PubMed1992

Enumeration of interleukin-1 alpha and beta producing cells by flow cytometry.

A technique for intracytoplasmic immunofluorescence staining to detect and quantify human interleukin-1 alpha (IL-1 alpha) and beta (IL-1 beta) in CD4, CD8, and CD14 positive lymphoid cells is described. Mononuclear cells stimulated in vitro with PHA to produce IL-1, were fixed and made permeable to antibodies by sequential exposure to paraformaldehyde and the detergent n-octyl-glucoside. Cytoplasmic and surface staining of both forms of IL-1 were demonstrated by indirect fluorescence using IL-1 beta and IL-1 alpha specific mouse monoclonal antibodies and quantified with flow cytometry.

Antigens, CD↗
PubMed1992

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis.

OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA). METHODS: Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls. RESULTS: Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin-1 beta (IL-1 beta) and IL-6. The corticotropin-releasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function. CONCLUSION: These findings suggest that RA patients have an abnormality of the HPA axis response to immune/inflammatory stimuli which may reside in the hypothalamus. This hypothalamic abnormality may be an additional, and hitherto unrecognized, factor in the pathogenesis of RA.

Adult↗