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Biomedical subjects

N D Hall

Publications and source records attributed to N D Hall.

At least 55 records · Page 3Linked to original sources
PubMed1986

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. IV. Increased numbers and activation of Facb-R+ cells after immunisation of healthy individuals.

Mononuclear cells expressing Fc gamma receptors that form Facb rosettes are increased in the peripheral blood of patients with rheumatoid arthritis compared with controls. Healthy individuals with a positive skin response to tuberculin showed a marked increase in numbers of circulating Facb-R+ cells three days after challenge, returning to baseline after seven days. No response was observed in subjects showing a negative skin test. A similar increase in Facb-R+ cell numbers was measured after intramuscular injection of another specific antigen, tetanus toxoid. In addition to this enhancement of Facb-R+ cell numbers, evidence has been obtained that these cells are in an activated state postimmunisation as judged by acquisition of low density and increased expression of class II MHC antigens. Apparently identical changes in Facb-R+ cell numbers and activation may be induced in vitro either by culturing sensitised mononuclear cells with specific antigen for three days or by an overnight incubation of normal cells with gamma-interferon (gamma-IFN). By analogy, therefore, the increased numbers of Facb-R+ cells in patients with rheumatoid arthritis are probably induced by gamma-interferon generated as part of an antigen driven immune response. In this context it is interesting that patients with Felty's syndrome, in whom neutropenia increases susceptibility to infections leading to the possibility of further stimulation of the immune system by micro-organisms, have particularly high levels of circulating Facb-R+ cells.

Arthritis, Rheumatoid↗
PubMed1985

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. II. Phenotypic characterisation of mononuclear cells forming Facb rosettes in RA.

We have previously reported an increased proportion of Facb-rosette forming cells in the peripheral blood of patients with rheumatoid arthritis in comparison with healthy controls. The present study investigates the surface phenotype of these cells by means of monoclonal antibodies and a variety of rosetting and lymphocyte fractionation techniques. Facb-R+ cells were found to lack surface markers characteristic of T and B lymphocytes. Studies with monoclonal reagents showed a positive reaction with OKIa1, OKM1, and another monocyte-specific antibody. Fac-R+ cells were recognised by anti-HLA-DR reagents but did not bind the monoclonal antibody 17.15 that recognises a determinant on HLA-DR antigens expressed by lymphocytes but not monocytes. These results show that Facb-R+ cells share certain surface characteristics with monocytes, though they are not phagocytic. These observations are consistent with an accessory role for Facb-R+ cells in the immune response.

Antibodies, Monoclonal↗
PubMed1985

Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. III. Immunoregulatory function associated with Facb rosette-forming cells.

A subpopulation of mononuclear cells (PBMNC) that expresses Fc receptors with specificity for the C gamma 2 region of IgG may be detected by rosette formation with calf erythrocytes coated with the Facb fragment of rabbit IgG. These Facb-R+ cells are found in increased numbers in the peripheral blood of patients with rheumatoid arthritis (RA). Studies have been carried out to identify the functional properties of these cells in healthy and rheumatoid subjects. Facb-R+ cells were shown to lack both natural killer and antibody-dependent cytotoxic activity. Depletion of Facb-R+ cells from both healthy and rheumatoid PBMNC resulted in a marked suppression of pokeweed mitogen (PWM) stimulated IgG synthesis but had no effect on T cell proliferation induced by phytohaemagglutinin, concanavalin A, or PWM. The addition of Facb fragments to PBMNC cultures also caused inhibition of PWM-driven IgG production. In this assay rheumatoid PBMNC were significantly less sensitive to Facb-mediated suppression than healthy control cells. Our results suggest that Facb-R+ cells are involved in the antibody-mediated feedback regulation of immunoglobulin synthesis and that this mechanism is impaired in patients with RA.

Antibody Formation↗
PubMed1984

The oxidation of serum sulph-hydryl groups by hydrogen peroxide secreted by stimulated phagocytic cells in rheumatoid arthritis.

Levels of free sulph-hydryl (SH) groups are depressed in the sera of patients with rheumatoid arthritis, especially during active disease. However, the mechanism underlying this effect is not known. We have investigated several oxidative species generated during the inflammatory process for their ability to react with serum SH in vitro. Our results show that serum oxidase enzymes (e.g. caeruloplasmin) do not have this activity but that "active oxygen species" generated either by an enzymatic reaction (xanthine plus xanthine oxidase) or by neutrophils stimulated with heat-aggregated IgG cause rapid oxidation of serum SH groups. The use of selective inhibitors of active oxygen species has demonstrated that this reaction is mediated by hydrogen peroxide. This compound is secreted in considerable amounts by activated phagocytic cells, especially neutrophils. Thus, serum SH levels may reflect phagocytic activity in patients with rheumatoid arthritis. We suggest that serum SH groups act as important extracellular scavengers of peroxides and so help to protect cells from damage by these molecules.

Arthritis, Rheumatoid↗
PubMed1984

Low density lymphocytes: their relationship to disease activity and to antirheumatic therapy.

The acquisition of low density by lymphocytes is the earliest detectable marker of their activation and may be utilized for the separation and quantification of these cells. Low density lymphocytes (LDL) are found in increased numbers in patients with rheumatoid arthritis compared with healthy controls (p less than 0.05). The number of LDL is raised in patients who failed to respond clinically to gold or D-penicillamine when compared with those who did respond (p less than 0.05), the latter group having LDL values in the normal range. Sequential studies have shown that successful antirheumatic therapy is associated with a return to normal LDL levels (p less than 0.01) and that any alteration occurs by three months. LDL are particularly associated with synovitis and there was a close correlation (p less than 0.01) with the Compound Thermographic Index in the sequential study, as well as with other markers of synovitis, but not with systemic disease. LDL thus appear to be important markers of the synovitis of rheumatoid arthritis and they may represent a population of lymphocytes closely involved in the maintenance of synovial inflammation.

Adult↗
PubMed1984

D-penicillamine withdrawal in rheumatoid arthritis.

Thirty-eight patients with rheumatoid arthritis in remission on penicillamine were entered into a prospective, randomised, placebo controlled study to determine the effects of gradual penicillamine withdrawal, to find a serological marker capable of predicting relapse, and to assess the effects of reintroduction of penicillamine. 80% of patients attempting gradual penicillamine withdrawal flared. There was no single serological marker capable of predicting outcome consistently. Decreasing SH levels were highly specific for recurrence of active synovitis but were insensitive. Reintroduction of penicillamine was successful. The implications of these findings, particularly concerning duration of therapy with disease modifying drugs, are discussed.

Arthritis, Rheumatoid↗
PubMed1984

Facb rosette-forming cells in mice: studies on their functional significance.

Lymphocytes bearing receptors for the Facb fragment of IgG have been shown previously to be elevated in the peripheral blood of patients with rheumatoid arthritis. The generation of these cells and their possible functional role in immune regulation have been investigated in mice. Facb rosette-forming (Facb-R+) lymphocytes were found to be elevated in the spleens of mice mounting a secondary plaque-forming cell (PFC) response to sheep erythrocytes but not during the primary response. Splenic Facb-R+ lymphocytes were also elevated when a cross-reacting antigen (goat erythrocytes) was used for the secondary immunization but not when a non-cross-reacting antigen (chicken erythrocytes) was used. Both primary and secondary immunization with bacterial lipopolysaccharide resulted in elevation of splenic Facb-R+ lymphocytes. Administration of antigen-specific Facb fragment in conjunction with antigen (calf erythrocytes) produced a suppression of the secondary PFC response. However, F(ab')2 fragments produced no such effect. This suppressive effect was shown to be antigen-specific since administration of Facb fragment of anti-calf erythrocyte IgG had no suppressive effect on the secondary PFC response to sheep erythrocytes. No change in splenic Facb-R+ lymphocytes was observed during delayed hypersensitivity responses to either sheep erythrocytes or the contact-sensitizing agent oxazolone. These results indicate that Facb-R+ lymphocytes are generated during secondary humoral responses but not cell-mediated immune responses, and suggest that these cells may exert a suppressive influence on antibody production. These findings are discussed in relation to the occurrence of these cells in patients with rheumatoid arthritis.

Animals↗
PubMed1984

Defective monocyte accessory function due to surface sulphydryl (SH) oxidation in rheumatoid arthritis.

Low serum sulphydryl (SH) levels are a feature of active rheumatoid arthritis (RA). We have investigated whether a similar blockade of membrane SH groups on mononuclear cells modifies the function of these cells in this disease. Using pokeweed mitogen stimulated IgG synthesis as the assay system, we have found that the accessory cell function of peripheral blood monocytes is totally dependent on free SH groups on the cell surface. Monocytes from patients with active RA display poor accessory cell function when compared with healthy monocytes or with cells from patients treated with D-penicillamine. The poor function of the rheumatoid accessory cells may be corrected in vitro by 2-mercaptoethanol (2-ME). Addition of 2-ME to the culture system also enhances IgG synthesis by rheumatoid mononuclear cells to normal levels. We suggest that surface SH-dependent mechanisms are responsible, at least in part, for the depressed mononuclear cell functions of rheumatoid cells in vitro and may explain some effects of D-penicillamine therapy in rheumatoid patients.

Arthritis, Rheumatoid↗
PubMed1983

Depressed exocytosis by rheumatoid neutrophils in vitro.

Polymorphonuclear leucocytes and monocytes have been isolated from the peripheral blood of patients with rheumatoid arthritis and healthy controls using Percoll gradient centrifugation. These cells have been tested for their ability to release superoxide anion and to undergo exocytosis following stimulation with heat-aggregated IgG. Monocytes from patients and controls react similarly in these assays but neutrophils from the patients release less beta-glucuronidase than do normal cells. This could not be related either to the expression of cell surface Fc receptors or to oxidative metabolism and does not appear to be an effect of the administration of non-steroidal anti-inflammatory drug therapy. It is suggested that rheumatoid neutrophils are not inherently defective but are less responsive to activation in vitro because of prior exposure to immune complexes in vivo.

Arthritis, Rheumatoid↗
PubMed1983

Heterogeneity of Fc gamma receptor expression on human cell lines.

Receptors for the Fc gamma portion of IgG (Fc gamma R) may be detected on several cell populations using a variety of assay techniques. The heterogeneity of these receptors on human cell lines has been investigated using a rabbit antiserum raised against Fc gamma R expressed on K562 cells. This reagent only partially inhibited Fc gamma R binding on K562 cells, but completely blocked that on Daudi cells. The results are compatible with the hypothesis that Daudi cells express only one form of Fc gamma R, which is similar if not identical to one of the 2 Fc gamma-binding activities detected on K562 cells. Cell lines may therefore be useful sources of different homogeneous Fc gamma R material for the development of reagents to study these receptors on cell subpopulations in health and disease.

Animals↗
PubMed1983

Effect of a specific iron chelating agent on animal models of inflammation.

Iron is an important catalyst of oxidative radical reactions and promotes the formation of the hydroxyl radical from the superoxide anion radical and hydrogen peroxide. The stimulatory effect of the hydroxyl radical on lipid peroxidation prompted the speculation that free iron may directly promote inflammation and that iron chelating agents may have useful anti-inflammatory properties. This hypothesis is tested in animal models of inflammation with a specific iron chelating agent, desferrioxamine. At low doses (6 . 6 mg/kg) intraperitoneal desferrioxamine stimulated the induction of acute foot pad swelling in rats by monosodium urate but at higher doses (above 200 mg/kg) it suppressed this inflammatory reaction. A similar anti-inflammatory effect was observed in carrageenan-induced foot pad swelling. In guinea-pigs in which a Glynn-Dumonde synovitis was induced with bovine gammaglobulin, desferrioxamine (100 mg/kg) stimulated the acute inflammatory induction phase of this chronic allergic monoarthritis model. Repeated administration of desferrioxamine (100 mg/kg) from the seventh to the twelfth day after intra-articular challenge with bovine gammaglobulin markedly depressed the chronic inflammatory phase. In-vitro experiments suggest that desferrioxamine inhibits iron-catalysed lipid peroxidation when it is poorly saturated with iron, but loses this effect when it is iron saturated. Such an effect may explain our results with desferrioxamine in the animal studies and suggests that effective iron chelation and its removal may modify the inflammatory process in man.

Acute Disease↗
PubMed1982

Circulating immune complexes in Crohn's disease. Their characterization and interrelationship with components of the complement system.

Of the sera from 55 patients with Crohn's disease, 37% showed evidence of anticomplementary activity, C3 and C4 levels were significantly increased in these patients compared with control subjects, although total hemolytic complement levels were normal. C3 inactivation products were demonstrated in 32.9% of serum and plasma samples from 51 patients with CD. This was taken to be evidence of in vivo activation of C3 and the complement system. Activation of the C' system was thought to be caused by circulating immune complexes since evidence of anticomplementary activity could be correlated with incidence of C3 activation. Gel filtration studies carried out on 15 serum samples (13 patients) showing anticomplementary activity showed this activity to be confined to two fractions of molecular weight range greater than 10(6) and 2 x 10(5) - 10(6) daltons. IgG and IgA were present in both these fractions. As the molecular weights of IgG and IgA are lower than the molecular weight range of these fractions, it is possible that the immune complexes were composed of IgG and possibly IgA complexed with antigen.

Adolescent↗
PubMed1981

The importance of iron in rheumatoid disease.

The hypothesis is that iron, which accumulates in rheumatoid synovial membrane and fluid contributes to the variable expression of rheumatoid disease in two ways. Firstly, it catalyses oxidative radical reactions which lead to the formation of the hydroxyl radical and subsequent lipid peroxidation. Hydroxyl radicals and lipid peroxidation cause extensive disruption of cellular and organelle membranes and promote inflammatory tissue damage. Secondly, the infiltration of the rheumatoid synovium by chronic inflammatory cells may be due not to an antigenic process but to the tendency for these cells, which have receptors for iron-binding proteins, to migrate towards deposits of iron.

Acute Disease↗
PubMed1981

Protection against superoxide and hydrogen peroxide in synovial fluid from rheumatoid patients.

1. On exposure of synovial fluid to superoxide and hydrogen peroxide, generated enzymically or by activated polymorphonuclear leucocytes, hyaluronic acid is depolymerized and the fluid loses its lubricating properties. The ability of synovial fluid from rheumatoid patients to scavenge superoxide and hydrogen peroxide was therefore examined. 2. Synovial fluid from a range of rheumatoid patients contained no superoxide dismutase activity, insufficient caeruloplasmin to scavenge any superoxide radical and little, if any, catalase activity. 3. Total ascorbate (reduced ascorbate + dehydroascorbate) concentrations in the plasma and synovial fluid of rheumatoid patients were similar in each case. The values are at the low end of the normal range. 4. These results are discussed in relation to the role of oxygen radicals in inflammatory joint disease.

Arthritis, Rheumatoid↗
PubMed1981

Characterisation of activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis.

The extent and nature of lymphocyte activation in the circulation in rheumatoid arthritis (RA) was investigated. Peripheral blood lymphocytes (PBL) from RA patients and healthy controls were separated into a number of discrete fractions by density in discontinuous Ficoll density gradients. Low density (activated) lymphocytes were found at significantly higher levels in RA, particularly in patients with clinically active disease. Conversely, patients with clinically inactive RA had normal levels of activated lymphocytes. Lymphocyte populations within the ficoll gradient fractions were detected by E rosettes, staining for surface Ig, and by different avidities of EA binding. The activated population in RA was shown to be relatively depleted of T cells, enriched in surface Ig-bearing lymphocytes, and depleted of lymphocytes with high avidity EA binding. The evidence suggests that many of the activated PBL in RA are B blasts.

Arthritis, Rheumatoid↗