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Biomedical subjects

M L Bliven

Publications and source records attributed to M L Bliven.

23 records · Page 2Linked to original sources

The mechanism of tumor allograft survival induced by CP-17,193.

CP-17,193 was examined in vivo for its immunosuppressive effects and for its promotion of E1(4) tumor allograft survival. At a dose of 10 mg/kg p.o., it was shown to suppress the development of both antibody-dependent and cellular cytotoxicity for E1(4) cells. After cessation of drug treatment, and in contrast to what is observed with cyclophosphamide, the humoral immune response was promptly restored. The restoration of cellular cytotoxicity followed a more protracted course, and the tumor allograft was not rejected by day 24. Three possible mechanisms of immunosuppression were examined. CP-17,193 was shown to inhibit the formation of IL-2 sensitive blasts. However, it had no effect on T cell proliferation using performed blasts in the presence of added IL-2, and it did inhibit IL-2 production. Its immunosuppressive effects might therefore be explained by an inhibition of some initial step of lymphocyte activation which interferes with the T lymphocyte's ability to progress on to cell division and IL-2 production after stimulation.

Animals↗

Effects of levamisole on the proliferation of thymic lymphocyte subpopulations.

The ability of levamisole to enhance proliferation of murine lymphocyte preparations stimulated by concanavalin A was examined. Levamisole substantially augmented the proliferation of C57Bl/6 thymic lymphocytes, but had only marginal effects on the proliferation of splenic lymphocytes. The possibility that this difference was related to the degree of cell maturation was examined by peanut agglutinin fractionation of the thymic lymphocytes. Levamisole was found to stimulate proliferation most effectively in the mature fraction. However, since the focus of levamisole activity might be on macrophages, also shown to be present in preparations of splenic and thymic lymphocytes and in both PNA separated fractions, the drug's activity was compared to several macrophage replacements: LAF-IL 1, 2-mercaptoethanol, and added splenic adherent cells. Added plastic adherent cells and 2-mercaptoethanol were effective in augmentation of proliferation of both mature and immature populations whereas LAF-IL 1 like levamisole was most effective on the mature population.

Animals↗

Anti-arthritic effect of bee venom.

Bee venom, administered subcutaneously, suppressed the development of carrageenan-induced paw edema and adjuvant arthritis in the rat in a dose-related manner. A single dose of bee venom administered subcutaneously the day before or on the day of injection of complete Freund's adjuvant (CFA) effectively suppressed the development of polyarthritis. This suppressive effect decreased progressively as dosing was delayed. Bee venom was found to be most effective when mixed and injected (sub-plantar) together with CFA, the disease-inducing agent. Similarly, antigens such as egg albumin, when incorporated into CFA, and injected into the hind paw, prevented the development of arthritis. These results suggest that at least two mechanisms are involved in the anti-arthritic action of bee venom: (1) alteration of the immune response, probably via antigen competition, and (2) an anti-inflammatory action via corticosteroids or through an as yet undetermined mechanism.

Animals↗

Effect of levamisole on the mitosis of murine thymocytes in culture.

The effect of levamisole on murine thymocytes stimulated by concanavalin A in culture was measured as the change in number of cells in the DNA synthetic phase (S-phase) and in number of cells undergoing mitosis (M-phase). Addition of levamisole to Con A-stimulated lymphocytes led to an approximately tenfold increase in the frequency of mitosis and a fivefold increase in the frequency of cells heavily labeled with thymidine. Thus, levamisole leads to an increased number of cells undergoing proliferation. Determination of cell viability excluded the possibility that the effect of levamisole was simply due to enhanced numbers of viable cells in culture. Examining the effect of levamisole on the proliferating cells alone, it was found that they had a shorter cell cycle time. It was therefore concluded that levamisole affects thymocyte proliferation in vitro in two ways: enhancement of the number of proliferating cells and shortening the cell cycle time of proliferating cells. A similar effect in vivo might be important in the mechanism of action of levamisole as an immunotherapeutic agent.

Animals↗