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Biomedical subjects

G D Pegrum

Publications and source records attributed to G D Pegrum.

At least 19 recordsLinked to original sources

Timing of cyclosporin-A therapy for abrogation of HVG and GVH responses in rats.

Treatment with cyclosporin A was most effective in abrogating popliteal-lymph-node enlargement induced by host-versus-graft and graft-versus-host reactivity in rats when started before injection of donor-strain lymphocytes. Popliteal lymph-node enlargement was never completely abolished, and splenic lymphocytes from recipients treated with cyclosporin A showed no significant reduction in their response to donor-strain lymphocytes in mixed lymphocyte cultures, suggesting that clonal deletion had not taken place. Mixed lymphocyte cultures also indicated that cyclosporin treatment had not reduced the antigenicity of recipient lymphocytes towards donor strain.

Animals

Anti-lymphocyte antibody levels in chronic lymphocytic leukaemia.

A radioimmunoassay for measuring levels of lymphocyte autoantibody in chronic lymphocytic leukaemia (CLL) has been developed. Antibody in the form of crude IgG was extracted from patients' sera and iodinated. The assay utilizes its cross-reactivity with other CLL cells. Levels were measured in 23 patients. The results show that an inverse relationship exists between the quantity of circulating CLL autoantibodies and the number of mouse red blood cell rosetting lymphocytes (M cells). The preliminary findings do not correlate with disease activity although it is our impression that patients who are maintaining higher levels of autoantibody and fewer M-rosetting cells have nonprogressive disease.

Antilymphocyte Serum

The clinical features and HLA associations of reactive arthritis associated with non-gonococcal urethritis.

Fifty-seven patients with arthritis associated with non-gonococcal genital infection have been studied. Synovitis characteristically affected one or a few joints, expecially the knee, ankle or metatarsophalangeal joints and was accompanied by tenosynovitis and enthesopathies--each in about one third of the patients. A quarter of the patients had ocular, cutaneous, or mucous membrane lesions (Reiter's syndrome). Although six patients developed a chronic or relapsing course, average duration of the acute episode in the majority was three to five months. Available evidence strongly suggests that infection following sexual intercourse, usually but not always with a new partner, was instrumental in the initiation of the disease. We have suggested the term 'sexually acquired reactive arthritis (SARA)' to emphasize the mode of acquisition of the disease, and note that similar syndromes are seen associated with gut infection. We consider that usage of the term Reiter's syndrome is correctly applied to only those cases which exhibited the characteristic triad of urethritis, arthritis and conjunctivitis with or without other cutaneous and mucous membrane lesions. Thirty-six of the 54 patients who were HLA typed (67 per cent) possessed the antigen HLA-B27. Of 30 who presented directly to a rheumatology unit 25 (82 per cent) were HLA-B27 positive. The other 24 patients initially attended a venereology clinic and only 11 (46 per cent) of these bore the antigen. This appears to reflect disease severity, HLA-B27 positive patients having a significantly longer duration of disease symptoms and a higher frequency of extra-articular manifestations, than those lacking this antigen.

Adolescent

Role of Chlamydia trachomatis and HLA-B27 in sexually acquired reactive arthritis.

Inflammatory arthritis, tendinitis, and fasciitis after non-specific urethritis ("sexually acquired reactive arthritis" (SARA)) was studied prospectively in 531 men with non-specific urethritis, with particular reference to the frequency of isolation of Chlamydia trachomatis and the presence of HLA-B27. Satisfactory cultures were obtained from the urethral swabs from 384 patients; and HLA typing was performed on 482, of whom 30 (6%) were HLA-B27-positive. Arthritis developed in 16 patients, and five of the 14 (36%) with satisfactory cultures were positive for C trachomatis; 135 of the patients without arthritis were also positive for C trachomatis, an identical proportion. Seven of the 15 patients (40%) with arthritis who were HLA-typed were HLA-B27-positive. Six of the 30 patients with HLA-B27 developed peripheral arthritis in contrast to only nine of the 452 patients lacking the antigen, suggesting a tenfold increase susceptibility. C trachomatis, however, was no more prevalent in cultures from HLA-B27-positive men than from the others. Thus carriage of C trachomatis is unlikely to be influenced by HLA-B27. C trachomatis may be an important pathogen in some cases of SARA but does not appear to be an exclusive trigger factor for this condition.

Arthritis

Immune complexes in myelofibrosis: a possible guide to management.

Using a fluorescent technique intracellular immune complexes were found in the peripheral leucocytes in all of 12 patients with myelofibrosis studied. Fluorescent cells varied from 12% to 81%; with no relation to the total white count or any obvious clinical finding. Three of the patients with severe refractory anaemia benefited from immunosuppressive therapy.

Antigen-Antibody Complex

Autoimmune antibodies in chronic lymphatic leukaemia.

In chronic lymphocytic leukaemia a factor in patients' serum enhances the in vitro viability of the abnormal cells and this has been identified as an antibody. The activity of this factor can be removed by interaction with anti-immunoglobulin and by ammonium sulphate precipitation with a degree of saturation in excess of 46%. Cohn fractionation and chromatography with A-50 Sephadex show that the factor is not a complex but an immunoglobulin. No activity is removed after reaction of sera with 2-mercapto-ethanol and di-thiothreitol. The evidence therefore suggests that a gamma-G immunoglobulin is involved. Concentrated washings from the leukaemic cells behave in exactly the same way as patients' sera and activity is retained in the same fraction during precipitation and purification procedure. The extensive cross-reactivity of the sera suggests a common chronic lymphatic leukaemic antibody and it is considered that an active autoimmune response may be an integral part of the disease.

Autoantibodies

Erythrophagocytosis by acute lymphoblastic leukaemic cells.

Phagocytosis of erthyrocytes and platelets by bone marrow blast cells has been noted in 4 patients in the late relapse of acute lymphoblastic leukaemia (ALL). The underlying mechanism is unclear but prolonged course of the disease seems to be a major factor in the emergence of cells with phagocytic properties.

Adolescent

Significance of mouse red cell rosette-forming lymphocytes in chronic lymphocytic leukaemia.

Increased mouse red cell (M) rosetting lymphocytes were demonstrated in the peripheral blood of patients with chronic lymphatic leukaemia. The range was wide, and patients showed considerable variation not only in the number of M cells but also in T and B rosetting lymphocytes. Treatment reduced M rosette lymphocytes proportionately as the total white count fell, and differential removal occurred only when the patients became leucopaenic. If we assume the M rosetting cells are the abnormal 'leukaemic' cells, treatment does not preferentially remove these. The M rosetting capacity appeared to be related to the presence of an immunoglobulin factor previously demonstrated on the cells and in the serum of patients with CLL which enhances in vitro viability of the leukaemic cells.

Animals

Immune complexes in myeloproliferative disorders.

A fluorescein-labelled anti-human immunoglobulin was used to demonstrate that peripheral blood from patients with myelofibrosis had a high proportion of phagocytic cells containing fluorescent immune complexes. Cells from patients with other myeloproliferative diseases (either chronic myeloid leukaemia or polycythaemia rubra vera) did not show similar intracellular immune complexes. Serum from patients with myelofibrosis incubated with polymorphs from healthy subjects caused the appearance of inclusions similar to those found when the patients' own cells were used, the healthy phagocytes apparently engulfing complexes from the patients' sera. The presence of platelets or complement did not alter the incidence of intracellular fluorescence. These tests may help in the diagnosis of myelofibrosis and may also be valuable in recognising the onset of this condition in patients with polycythaemia rubra vera.

Antigen-Antibody Complex

Restoration of "normal" membrane function in CLL cells by patients' serum.

Direct labelling of cell surface protein with 125I has enabled measurements to be made of lymphocyte membrane turnover. In CLL cells this is evidently much retarded in comparison with normal lymphocytes and it was thought that slow replacement of cell surface proteins might be responsible both for lack of membrane mobility and poor immunological responses. Serum from CLL patients has been found to enhance viability of the leukaemic cells in culture and the interaction of these serum factors with the CLL cell membrane gives rise to rapid replacement of surface proteins. Thus the rate of membrane turnover in vivo would be comparable with that of normal lymphocytes. Lack of cell-surface mobility and poor membrane biosynthesis can not be held responsible for poor immunological activity in vivo and it is suggested that autoimmune antibodies binding to the surface of CLL cells may spatially inhibit activation by ligands.

Cell Membrane

Lymphocyte surface membrane changes in dividing cells and following regidification with mitogens.

Iodination of surface membrane protein has allowed the dynamics of lymphocyte surface membrane protein to be examined. A comparison has been made between the rate of membrane turnover in fresh peripheral blood lymphocytes and lymphocytes in other states. When receptor redistribution is inhibited with high concentrations of mitogens, 'rigidification' of the membrane occurs and protein turnover is very much reduced. Loss of surface membrane protein is also much slower in lymphocytes which have been stimulated with mitogens and are undergoing active DNA synthesis. It is thought that these observations may relate to immunological inactivity and may have implications for pathological unresponsiveness.

Cell Membrane