An inhibitor of DNA synthesis produced by established lymphoid cell lines.
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Animals↗
Biomedical subjects
D H Vesole
Publications and source records attributed to D H Vesole.
Active and suppressor T cells: diminution in a patient with dyskeratosis congenita and in first-degree relatives.
Active, total and nonspecific suppressor T cells were studied in a 15-year-old black male with dyskeratosis congenita syndrome, a precancerous mucosal disease, and in 7 siblings and several other relatives in three generations. The propositus and 1 elder sister, products of a second-cousin marriage, died with dyskeratosis congenita. The mother had dermatomyositis, and the maternal grandmother and her sister reportedly had rheumatoid arthritis. Studies of available siblings, father, and grandparents revealed a high incidence of deficiency in number of active and/or suppressor T cells, sometimes severe enough to result in a decrease in total T cells. The patient had many stigmata of precocious aging, as did the sibling who died with the same syndrome. The laboratory data suggest that a defect in cell-mediated immunity, involving mainly or exclusively suppressor T cells, is associated with, and is presumably the cause of, precocious aging; perhaps an abiotrophy in this cell subpopulation results in physiologic aging.
Adolescent↗
Activation of human lymphocytes by supernatants from human thymic epithelium.
Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS.
Cells, Cultured↗
Stimulators and inhibitors of lymphocyte DNA synthesis in supernatants from human lymphoid cell lines.
Some T and B lymphoid cell lines (LCL) were found to secrete into their supernatants a substance able to stimulate lymphocyte proliferation. This substance produced an increase in [3H]thymidine uptake by mononuclear cells when added to unstimulated cultures (mitogenic effect) or when added to cultures stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) (potentiating effect). When complete supernatants were used, the potentiating effect was sometimes masked by an inhibitor of DNA synthesis. Fractionation on Sephadex G-100 separated these two activities. The stimulatory substance eluted at a m.w. range of 15,000 to 30,000, and the inhibitor eluted with the albumin peak. B cells with or without monocytes were the most sensitive to the mitogenic effect, whereas T cells were unaffected. Responses to PHA and PWM were potentiated when T cells were present, but the maximum effect was observed when the proportion of T cells was less than 50%. The stimulatory material may be similar to lymphocyte mitogenic factor and may function as a T cell-replacing factor in B cell stimulation.
Cell Line↗
Inhibitory effects of extracellular products from oral bacteria on human fibroblasts and stimulated lymphocytes.
Extracellular products of 12 strains of Streptococcus mutans and 5 additional species of oral bacteria were analyzed for their ability to inhibit proliferation of fibroblastoid cells (HeLa and AV3) and blast transformation of human peripheral blood lymphocytes obtained from normal individuals. Products from S. mutans strains AHT and BHT, Streptococcus intermedius, and Actinomyces viscosus inhibited [3H]thymidine uptake by fibroblastoid cells and phytohemagglutinin-stimulated lymphocytes. Products from S. mutans E49, Streptococcus salivarius, and Actinomyces naeslundii inhibited blast transformation of human lymphocytes but did not significantly inhibit the growth of fibroblastoid cells. Preparations from S. intermedius gave the greatest inhibitory activity against both target cell types; initial characterization of this preparation suggested a single factor active in both assays, in that the heat lability and Sephadex G-200 elution profile were similar for the inhibitory activity seen with the two cell types. The molecular weight of the inhibitor, estimated by gel filtration on Sephadex G-200 and Ultragel AcA34, was approximately 160,000. The results strongly suggest that oral bacteria produce heat-labile substances that interfere with fibroblast proliferation and alter the lymphocytic immunological response.
Actinomyces↗
Multiple myeloma: an old disease with new hope for the future.
Multiple myeloma is a currently incurable malignancy of terminally differentiated plasma cells. It typically occurs in older patients (median age 71 years). Clinical manifestations result from monoclonal protein (immunoglobulin) production and its accumulation in the serum and/or urine, anemia, lytic bone disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells have low proliferative activity--most myeloma experts opine that the initial oncogenic event occurs 10-15 years before clinical disease manifestation. In addition, myeloma cells develop multiple chromosomal abnormalities, which may explain the native resistance of myeloma patients to conventional therapy and our inability to completely eradicate the disease. Indeed, with conventional therapy, only 5% of patients achieve complete response. Minimal improvement has been observed with conventional therapies over the past 20-30 years; the median duration of initial response remains approximately 18 months with median survival in the 36-month range. However, recent clinical trials have established high-dose therapy with autologous hematopoietic stem cell transplant as superior to conventional therapy: complete remission rates of 25-30% can be affected with median survival exceeding 5 years. Newer approaches to improve treatment outcomes are in active clinical trials including: more potent induction regimens utilizing thalidomide, alone or in combination with dexamethasone; tandem transplants to improve complete remission rates; newer approaches to maintenance therapy using thalidomide with corticosteroids; non-myeloablative therapy with allogeneic transplant; and post-transplant vaccinations.
Bone Marrow Transplantation↗