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Biomedical subjects

M Salmon

Publications and source records attributed to M Salmon.

At least 145 records · Page 8Linked to original sources
PubMed1988

Sulfasalazine treatment and lymphocyte function in patients with rheumatoid arthritis.

Sulfasalazine is now an established 2nd line agent in the treatment of rheumatoid arthritis (RA) but its mode of action is unknown. Two separate studies have investigated the possibility that it works in RA by influencing lymphocyte function. After 12 weeks of treatment with sulfasalazine, elevated levels of circulating activated lymphocytes and abnormal ex vivo mitogen response to concanavalin A (Con-A) in 11 patients with RA reverted to normal. An in vitro study investigated the effect of sulfasalazine and its metabolites on mitogen response by healthy and RA peripheral blood mononuclear cells (PBMC). Sulfapyridine (SP) and 5-hydroxy SP suppressed the response of RA PBMC to Con-A. Sulfasalazine, SP and N-acetyl SP suppressed the response of healthy PBMC to pokeweed mitogen. 5-aminosalicylic acid also affected mitogen response and cell viability, which may be relevant to actions of this metabolite within the gut.

Aminosalicylic Acids↗
PubMed1988

A cellular deficiency in the rheumatoid one-way mixed lymphocyte reaction.

Activated lymphocytes expressing transferrin receptors (TFR) are present in the peripheral blood in rheumatoid arthritis. Characterization of these cells shows a CD4 dominance with depressed expression of CD8 and NK antigens, similar to synovial infiltrates. In the present study, one-way mixed lymphocyte reactions were performed to compare the response of rheumatoid patients with that of normal individuals. The TFR+ cells generated were characterized by double-label immunofluorescence. The TFR+ cells from rheumatoid responders showed elevated CD4+ cells and depressed CD8 and Leu-7 (NK) expression compared with normal, throughout the response. This defect was corrected by adding recombinant interleukin 2 at the beginning of the culture period. CD8+ cells stimulated to express TFR following interleukin 2 supplementation of the rheumatoid responses co-expressed HLA-DR. Functional studies indicated that TFR+ CD8+ cells were not cytotoxic, indirectly suggesting them to be suppressor cells. These findings indicate that significant immunoregulatory abnormalities in rheumatoid arthritis may reflect abnormal interleukin 2 biology.

Adult↗
PubMed1988

Deficient interleukin 2 production in rheumatoid arthritis: association with active disease and systemic complications.

Interleukin 2 (IL-2) production and proliferative responses of peripheral blood mononuclear cells (PBMC) stimulated with three concentrations of PHA were measured in 75 patients with rheumatoid arthritis (RA) and 25 normal controls. All patients were on a standard therapeutic regime, and were assessed for disease activity by clinical and laboratory criteria. Rheumatoid cells showed significantly lower IL-2 production and proliferation than normal PBMC at all PHA doses. These differences were not attributable to different kinetics. Within the rheumatoid population, both IL-2 levels and proliferation were lower in patients with active disease than those with inactive RA. Patients with extra-articular disease showed the most pronounced defects. Proliferative responses showed an inverse correlation with clinical indices of disease activity but not with measures of the acute phase response. Rheumatoid patients had higher proportions of CD4+, TFR+ and Tac+ lymphocytes than controls. Both proliferative responses and IL2- levels showed a positive relationship with the proportion of CD4+ cells, and an inverse relationship with Tac+ lymphocytes. Monocyte depletion and partial reconstitution resulted in an increase of both proliferation and IL-2 production, which was more marked in RA patients, suggesting that depressed IL-2 production may relate in part to monocyte effects. However, this cannot completely explain the magnitude of the defects observed, because normal monocytes did not increase the responses of rheumatoid lymphocytes, neither did rheumatoid monocytes suppress the responses of normal lymphocytes.

Adult↗
PubMed1988

Interleukin-2 production and response by helper T-cell subsets in man.

This study investigated the production of, and response to, the lymphokine interleukin-2 (IL-2) by functional subsets of human CD4+ T lymphocytes. Fresh peripheral blood mononuclear cells (PBMC) were sorted into CD4+2H4+/4B4- suppressor-inducer cells, and CD4+2H4-/4B4+ helper cells. The suppressor-inducer subset proliferated well in response to the T-cell mitogens concanavalin A (Con) A and phytohaemagglutinin (PHA), and produced IL-2. The helper cells produced no detectable IL-2 and proliferated poorly. However, the latter population were induced to express functional IL-2 receptors by Con A or purified protein derivative (PPD), and proliferated well if supplied with exogenous rIL-2. These findings suggest that the two functional CD4 subsets are not independent, or counteracting, but rather that the generation of T-cell help is likely to involve cooperative interactions between the two subsets.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Reactive oxygen species selectively deplete normal T lymphocytes via a hydroxyl radical dependent mechanism.

Chronic inflammatory synovitis is characterized by both lymphocytic infiltrates and persistent polymorph exudates. Activated polymorphs release reactive oxygen species (ROS) during inflammation, but the contribution that these make to the lymphocyte abnormalities associated with RA has been little studied. We therefore investigated the cytotoxic effects of the reactive oxygen species on human peripheral blood mononuclear cells (PBMC). PBMC were exposed to RPMI 1640 medium previously irradiated for up to 60 min. Consistent dose-dependent killing was observed at 24 h. Antioxidant studies indicated that H2O2 was the effective species. Catalase, which specifically degrades H2O2, gave almost total protection against cell death, while superoxide dismutase (SOD), thiourea, and mannitol were largely ineffective. Addition of exogenous H2O2 caused an identical pattern of cell death to that observed with irradiated medium. PBMC cultures supplemented with desferrioxamine (a ferric iron chelator) also gave significant protection, suggesting that H2O2 mediated its effects via OH radicals. Analysis of lymphocyte subpopulations showed that ROS caused a selective depletion, depending on the level of H2O2 present. Low levels induced a specific loss of CD8+ cells, while higher concentrations caused significant loss of CD4+ T cells as well. sIg+ B cells were unaffected at either concentration. This selective lymphotoxic effect of ROS may be of considerable importance in the pathogenesis of autoimmune inflammatory disease.

Adult↗
PubMed1987

Modes of action of second-line agents.

The slow acting anti-rheumatic drugs (SARDS) are a chemically heterogeneous group. They produce a more profound effect on clinical and biochemical aspects of rheumatoid arthritis than do the aspirin-like non steroidals. The similarities in their clinical effects suggest that they have a common mode of action. Review of the known activity of SARDs on different cell types at various anatomical sites suggest that in fact different SARD drugs act in differing and sometimes conflicting ways. The site of action of SARDs within the body--whether at the level of synovial inflammation or of the systemic immune response--is largely undetermined. The effects produced by a single agent in vivo and in vitro are not always the same so a single mode of action, for example through possession of a thiol group, cannot explain the effects of all SARDs. Indeed a single agent such as aurothiomalate may show multiple effects and the same is now shown to be true for the newer agent sulphasalazine. A unifying hypothesis is put forward to explain the clinical similarities but different cellular effects. It is proposed that all SARDs act on some aspect of the central reaction in the ongoing immune response where antigen presentation to T helper cells results in interleukin 2 production and the generation of activated T cells. The precise site affected in this cell to cell/monokine reaction will vary between drugs, but the overall effect of blocking this will be similar for all drugs, both in short term clinical benefit and in the problem of disease flares after withdrawal of therapy.

Anti-Inflammatory Agents↗
PubMed1987

Natural killer cells in peripheral blood and the mixed lymphocyte response: interaction with the transferrin receptor.

Several reports suggest that natural killer (NK) cells recognize the transferrin receptor (TFR) as a target for killing, and that natural cytotoxicity may be involved in the control of stem cell proliferation in bone-marrow. This study tested whether NK-cell recognition of the TFR on activated lymphocytes plays a role in the control of peripheral immune responses. Six lymphoid lines were created from a single individual, and used as targets for cytotoxicity assays, using either peripheral blood mononuclear cells, or mixed lymphocyte reaction (MLR)-derived effectors. The cells responsible for killing were predominantly Leu-11+Leu-7+ NK cells, though CD3+ cells accounted for about 25% of cytotoxicity from MLR. No correlation was observed between TFR density and NK susceptibility when using all six cell lines. Specifically increasing the density of TFR on a single cell line failed to increase susceptibility to NK, suggesting that the TFR does not act as a major target for natural cytotoxicity directed at lymphoid cells. Furthermore, the relatively low levels of killing observed indicate that activated NK populations that accumulate at sites of immune response are unlikely to play a direct immunoregulatory role.

Antigens, Surface↗
PubMed1986

Comparison of smear and imprint techniques for rapid diagnosis in neuro-oncology.

The smear and imprint techniques were applied to brain tumor biopsy specimens and the resultant preparations compared for preservation of architecture and cell morphology. The imprint gave excellent detail of cell morphology and good preservation of architecture, especially in soft tumors. The method has enabled a rapid diagnosis to be made in 100 cases of intracranial lesions and is a valuable complement to smear and cryostat sections.

Adenoma, Chromophobe↗
PubMed1986

Takayasu's arteritis: a pathogenetic role for cytotoxic T lymphocytes?

Takayasu's arteritis is an inflammatory panarteritis of unknown aetiology affecting large elastic arteries. We examined a segment of abnormal common carotid artery removed at by-pass surgery from a 23-year-old man with typical angiographic features of Takayasu's arteritis. Using monoclonal antibodies we were able to demonstrate marked infiltration of the arterial wall with OKT8 positive lymphocytes (suppressor/cytotoxic cells) but not with OKT4 positive lymphocytes (helper cells). Studies of circulating lymphocytes showed increased numbers of "activated" cells and increased in vitro cytotoxicity against cultured human umbilical cord endothelial cells, compared to normal lymphocytes. Cellular immunological mechanisms may play an important role in the pathogenesis of Takayasu's arteritis, possibly through the direct action of cytotoxic T cells on large elastic arteries.

Adult↗
PubMed1985

A comparison of methods for enumerating lymphocyte classes.

We have evaluated a novel kit method for enumerating B and T lymphocytes using antibody-coupled beads. The technique proved to be an unsuitable alternative to sheep red blood cell rosettes and immunofluorescence. However, the principle is potentially valuable and we suggest certain modifications which would make the method more suitable for routine use.

Animals↗
PubMed1985

Transferrin receptor expression by stimulated cells in mixed lymphocyte culture.

Transferrin receptor (TRFr) expression by cells in mixed lymphocyte culture increases steadily for the first 5 days, but then reaches a plateau. By the sixth day in culture, about 20% of viable cells express TRFr in two-way mixed lymphocyte reactions. This subpopulation of TRFr-positive cells represents the proliferating population; it is heterogeneous, containing T-cell blasts and smaller cells which are a mixture of T and non-T cells. A small group of non-T cells have phenotypic similarity to natural killer (NK) cells. T cells appear to divide earlier in the course of the response than non-T cells. The biphasic nature of this response and the slower non-T reactivity may be due to a secondary stimulation of non-T cells by factors released from activated T cells (such as interleukin-2).

Antigens, Surface↗
PubMed1985

Transferrin receptor bearing cells in the peripheral blood of patients with rheumatoid arthritis.

Activated, proliferating lymphocytes are a feature of rheumatoid arthritis. They are present both in the synovial membrane and in the peripheral circulation. The expression of transferrin receptors(TFR) is a good marker of cellular proliferation. This study shows increased levels of circulating TFR-bearing lymphocytes in patients with rheumatoid arthritis (RA). The TFR+ population contains a disproportionately large number of T4+ cells, leading to a high T4:T8 ratio (5:1 in the TFR+ population, compared to 2:1 in the total circulating pool of lymphocytes). This reflects the pattern found in the rheumatoid synovium and suggests that lymphocyte activation in RA may be an extra-articular phenomenon. The TFR+ population also contains a range of non-T cells, including B cells, and a population bearing phenotypic similarities to natural killer (NK) cells.

Antigens, Surface↗
PubMed1984

The use of cytocentrifuge preparations for the demonstration of T cell surface antigens.

Cytocentrifuged cell preparations have been evaluated as substrates for the demonstration by immunofluorescence of T cell surface antigens. Results obtained by a 2-stage method with fluorescent conjugate specific for the isotype of the first stage monoclonal antibody, and by a 3-stage procedure employing an intermediate antiserum to mouse IgG as amplifying agent, showed good correlation with those obtained by a standard technique performed on cells in suspension. These methods have the advantages of requiring fewer cells and less antibody and the cytocentrifuge preparations may be stored for batch assay.

Animals↗
PubMed1984

Platelets in the synovial fluid of patients with rheumatoid arthritis.

In a study of synovial fluid from 110 patients with various forms of arthritis, platelets were identified in the synovial fluid of all the 50 rheumatoids, in 18 out of the 25 (72%) with osteoarthritis and in all 35 of those with other forms of inflammatory osteoarthrosis. Identification of platelets by light microscopy was confirmed by electron microscopy. Platelet counts were significantly higher in rheumatoid fluid (mean 14 988/mm3; range 1000-65 000/mm3) compared with fluid from patients with osteoarthrosis (mean 1 592/Mm3; 0-10 000/mm3). In addition, significantly higher platelet counts were found in the synovial fluid (SF) of inflamed joints. There was a positive correlation between the SF platelet count and the total white cell count, polymorph count, hydrogen ion concentration, knee score, acid phosphatase and 5-nucleotidase activity and a negative correlation with the glucose level. All these factors indicate joint activity. Finally, platelet numbers correlated with SF levels of immunoglobulin M, and seropositive patients had significantly higher platelet counts in the SF compared with seronegative patients. Rheumatoid patients with thrombocytosis also had higher SF platelet counts. The close relationship of the SF platelet count to other indices of inflammation supports the concept that platelets may directly contribute to synovial inflammation by a variety of pathways.

Arthritis↗