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Biomedical subjects

G D Pegrum

Publications and source records attributed to G D Pegrum.

At least 37 records · Page 2Linked to original sources

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↗

Influence of HLA matching and blood-transfusion on outcome of 502 London Transplant Group renal-graft recipients.

The outcome of 502 cadaver kidney transplants has been followed for up to six years; these grafts were arranged through the Tissue Immunology Unit of the London Hospital Medical College, the coordinating centre of the London Transplant Group. An analysis of HLA (A and B) recepient-donor matching revealed, as in previous analyses, clear differences (now highly significant) between the best as compared with the lesser matched recipients. A quarter of the patients (group 4 and 3a) had a superior outcome 20-30% greater than poorly matched (2 or less group) which constituted 53% of individuals. The results in the 3b group (28% of patients) were intermediate 10-15% better than the "2 or less antigens in common" group. A small number of recipients mostly 4 or 3 matched who were retrospectively HLA-D matched showed an even better graft survival. The effect of blood-transfusion before transplantation was studied and found to improve the outlook especially in the best-matched groups. No difference was apparent between those receiving less or more than ten units except in a group of patients with cytotoxic antibodies and/or retransplants. This "immunocompetent-presensitised" group had the best outcome provided these recipients had few transfusions and were subsequently well matched. These findings emphasise the continued need for successful collaborative associations, so that improved matching can be achieved which if universally applied would ensure better graft survival for a large number of patients in renal failure.

Binding Sites, Antibody↗

Serological identification of Ia antigens: report of a British region Ia workshop.

In preparation for the 7th International Histocompatibility Workshop 13 laboratories in the British Region participated in a local workshop. One hundred and twenty-three sera which had been previously shown to have activity on either normal B cells, CLL cells or B cell lymphoid lines in the absence of HLA-A, B or C activity were exchanged between the laboratories. These sera were tested on a total of 212 B cells, 101 CLL cells, 76 T cells and 76 lymphoid cell lines. The data was collected and analyzed in Oxford. The analysis showed that six groups of sera could be distinguished. When these groups were compared with the D locus typing of some of the lymphoid lines which were derived from individuals used as MLC typing cells, they were seen to have significant associations with D locus antigens. The serological groups defined were therefore given numbers corresponding to the D locus numbers they associate with, i.e. UK1 is associated with DW1 and so on for UK2, 3, 4, 5 and 7. Comparison of typing techniques showed that long incubation both with antiserum and then with complement, 1 hour + 2 hours gave the best and most reproducible reactions on normal B cells. Residual anti-HLA-A, B or C activity in some of the sera even after platelet absorption showed the importance of adequate checking on T cells after absorption.

Antibody Specificity↗

Lymphocyte stimulation by soluble subcellular fractions.

Nuclear material can produce inhibition or stimulation of healty leucocytes under different experimental conditions, Reactivity could not be produced in cultures using intact nuclei and allogeneic lymphocytes. The effect of nuclear and cytoplasm fractions was compared with that of whole cells on intact healthy lymphocytes. The HLA activity in the individual fractions was assessed. Stimulation was produced by certain nuclear and cytoplasmic fractions and these were closely related to the peaks of HLA activity. The response to these fractions showed less activity than that achieved in conventional one way MLC tests.

Cell Fractionation↗

Skin reaction and antibody responses in guinea-pigs sensitized to human leukaemia cells or their nuclei in combination with Bacillus Calmette-Guérin.

Guinea-pigs sensitized by subcutaneous injection of chronic lymphatic leukaemia (CLL) cells combined with Bacillus Calmette-Guérin (BCG) displayed good skin reacitons 24 and 48 h after challenge with CLL cells. Equally good responses were also demonstrated using nuclei from the leukaemic cells in combination with BCG. These reactions were significantly greater than those produced in the same manner but without BCG. Sera form the animals were examined for the presence of antibodies against CLL cells by cytotoxicity and immunofluorescence techniques. Only samples from guinea-pigs innoculated with CLL cells were found to contain significant antibodies. Histological examination showed that whereas leukaemic cells persisted at the sensitizing injection site leukaemic cell nuclei could not be visualized. It is suggested that because leukaemic cell nuclei in combination with BCG are able to induce good skin reactivity without provoking a vigorous humoral antibody response they may have possible advantages over leukaemic cells when used for immunotherapy.

Animals↗

Pretreatment with antilymphocyte globulin and donor cells on graft prolongation in an experimental model and some observations on graft-versus-host reaction.

Survival of Lewis X Brown Norway F1 renal allografts was prolonged in Lewis recipients by pretreatment with small numbers of donor marrow cells and low dose antilymphocyte globulin(ALG)in combination. Either marrow cells or ALG alone were ineffective at these doses. It was also shown that pretreatment with marrow cells and antilymphocyte serum (ALS) considerably suppressed the local graft-versus-host reaction.

Animals↗

Bone marrow appearances in reticulum cell sarcoma.

18 patients with malignant lymphoma "histiocytic type" were investigated for the bone marrow involvement. Bone marrow aspirates and needle biopsies were used. Smears and sections of the aspirates were examined. The findings in the sections of both aspirates and biopsies were complementary and far more valuable than the bone marrow smears alone. It is concluded that bone marrow examination is helpful in determining the spread of the disease and should be repeated during the course of lymphoma.

Adult↗