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J H DuBois

Publications and source records attributed to J H DuBois.

5 recordsLinked to original sources

The production of prostaglandin and the regulation of cell division in neonate rat primary mixed glial cultures.

The production of prostaglandins has been studied in neonate rat primary mixed glial cultures. A correlation was found between inhibition of [3H]thymidine incorporation in the cultures and production of prostaglandin, which was stimulated by the addition of supernatant from Con A-activated rat splenocytes. Inhibition of prostaglandin synthesis in the cultures by indomethacin results in a striking increase in incorporation of [3H]thymidine into the cultures, an effect which was reversed by the addition of exogenous PGE2, but not PGF2 alpha. PGE was the principal prostaglandin detected, with both macrophages/microglia and astrocytes contributing to the output. A possible role for prostaglandins in the modulation of inflammatory responses in the central nervous system is discussed.

Animals↗

Expression of major histocompatibility complex antigens in neonate rat primary mixed glial cultures.

Primary mixed glial cultures containing astrocytes, oligodendrocytes and macrophages have been cultured from cerebral hemispheres of neonate rats and examined by indirect immunofluorescence for the expression of class I and II RT1 major histocompatibility complex-coded antigens. None of these cells expressed detectable levels of either class I or II antigens except for the macrophages which were weakly class I positive. Treatment with lymphokine-containing supernatant from concanavalin A-activated splenic lymphocytes resulted in increased expression of class I antigens on all cells together with the appearance of class II RT1.B and RT1.D antigens on macrophages and a small proportion of type 1/protoplasmic astrocytes. The identity of the Ia antigens was confirmed by immunoprecipitation from lysates of surface-iodinated cells. The ability of lymphokine-treated mixed glial cultures to stimulate proliferation of allogeneic lymphocytes provides additional evidence of Ia induction. A possible role for these Ia+, putative antigen-presenting cells in delayed type hypersensitivity in the central nervous system is discussed.

Animals↗

Regulation of lymphocyte activation by PGE2 in multiple sclerosis.

The immunoregulatory action of prostaglandin E2 (PGE2) was examined in two independent lymphocyte activation assays of peripheral blood lymphocytes obtained from multiple sclerosis (MS) patients and normal controls. Phytohaemagglutinin (PHA)-mediated stimulation of lymphoblast transformation and leucocyte migration inhibition factor (LIF) release were both inhibited by PGE2 in a dose-dependent manner. Sixteen patients with MS were studied as a single clinical group and their PHA-stimulated lymphocytes shown to respond essentially normally to PGE2. Four patients in relapse exhibited diminished responsiveness in both assays, but only at a supraphysiological concentration of PGE2. Thus, unresponsiveness to immunoregulatory prostaglandins is unlikely to be a major contribution to the immunopathogenesis of MS.

Adult↗

Phosphorylated lymphocyte plasma-membrane proteins.

Lymphocytes were labelled by incubation with [32P]Pi and their plasma membranes isolated. Analysis by one-dimensional and two-dimensional gel electrophoresis revealed a small number of strongly phosphorylated polypeptides. Two of these were especially prominent; they had molecular weights of about 52000 and 90000, were acidic and were apparently not glycosylated. Similar patterns were obtained for quiescent T- and B-lymphocytes from different species and for cultured lymphoblastoid cells, although the relative amounts of the labelled polypeptides varied. Immunoprecipitation analyses of the detergent-solubilized 32P-labelled plasma membranes indicated that the glycosylated polypeptide of the human major transplantation (HLA-A and HLA-B) antigens and its mouse and pig counterparts are phosphorylated. In contrast, no phosphorylation of the membrane-associated immunoglobulin, the mouse Thy-1 antigen or the human HLA-DRw(Ia) antigen was detected. The phosphorylation patterns of human peripheral blood and nude-mouse spleen lymphocytes did not change during the period 5-30min after mitogen stimulation. Therefore a change in the phosphorylation of plasma-membrane protein(s) is probably not an early biochemical event in the initiation of T-lymphocyte and B-lymphocyte growth, although a rapid transient change cannot be ruled out. Similar plasma-membrane phosphorylation patterns were also obtained by incubating the purified plasma membrane with [gamma-32P]ATP. The phosphorylation of the 90000-mol.wt. polypeptide was particularly rapid and was stimulated by the addition of cyclic AMP.

Animals↗