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Biomedical subjects

I Florentin

Publications and source records attributed to I Florentin.

At least 73 records · Page 4Linked to original sources

Cellular and humoral immunity to leukemia cells in BCG-induced growth control of a murine leukemia.

The antitumor effects of weekly iv injections of 1.0 mg BCG and/or sc injections of 10(7) irradiated leukemia cells were studied in an isogeneic, transplantable lymphoid leukemia in the C57BL/6 mouse. The injections were started at day 1 after ip inoculation of 10(5) leukemia cells. BCG prolonged the survival time of most animals and cured 22%. BCG plus irradiated cells cured only about 10% of the mice, and irradiated cells alone had no curative effect. Individual tumor-bearing mice in the various experimental groups were examined with respect to ascites tumor cell number; complement-dependent cytotoxic antibodies in sera; direct and antibody-dependent cytotoxicity to tumor cells of lymphoid cells from peritoneal fluid, the spleen, and peripheral lymph nodes; and the cytology of ascites, the spleen, and lymph nodes. Only the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) was correlated with the ascites tumor cell number, since the ADLMC was high only in mice with a tumor cell number less than that of the controls. Furthermore, since mice with a low tumor cell number had predominantly only lymphocytes as the nonmalignant cell type in their peritoneal fluid, ADLMC may have had an important role in BCG-induced control of tumor growth.

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Heat-killed Pseudomonas aeruginosa as a systemic adjuvant in cancer immunotherapy.

The effect of heat-killed Pseudomonas aeruginosa (10 serotypes) on antibody formation, macrophage activation and leukemia growth was investigated in relation to the dose injected and to the time and the route of administration. It appeared that intravenous administration of the preparation (10(9) bacteria per ml) was the most efficient at the dose of 0.1 ml since: 1) it increased the number of PFC against SRBC when injected 10 days before the antigen (higher doses and shorter time intervals resulted either in no modification or an significant inhibition of the PFC response; 2) it induced a slight activation of peritoneal macrophages as measured by their cytostatic activity for tumor cells in vitro, when injected 3 or 7 days before testing whereas higher doses were ineffective; 3) it increased the survival time of leukemic mice when administered 2.5 days before the injection of L1210 tumor cells, and higher doses were also effective in this immunoprophylaxis assay. When the subcutaneous route was used, large doses appeared to be the most effective: 1) potentiation of the PFC response was obtained only when 0.5 or 0.2 ml were given 10 days before the antigen; 2) macrophage activation was demonstrated 7 and 10 days after 0.5 ml; 3) leukemia growth was retared when 0.5 or 0.2 ml was injected 2.5 days prior to L1210 tumor cell inoculation and also when 0.2 and 0.1 ml were injected 7 days before tumor cells. No correlation between macrophage activation and the inhibition of tumor growth could be found.

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Further purification and chemical characterization of the lymphocyte-inhibiting-factor extracted from thymus (LIFT).

A thymic extract which was previously demonstrated to contain a lymphocyte-inhibiting-factor (LIFT) based on its immunosuppressive activity in vivo and its antiproliferative properties on lymphocytes in vitro, has been purified using ultrafiltration procedures. Most of the activity measured by the ability to inhibit DNA synthesis in short term cultures of mouse thymocytes, was recovered in the 10,000-50,000 m. wt fraction (I fraction). In contrast, similar extracts from non-lymphoid organs were always ineffective in decreasing DNA synthesis in thymocytes. The I fraction was also inhibitory of DNA synthesis in mouse spleen cells stimulated by PHA whatever the time at which the fraction was added after the mitogen stimulation. This fraction, as well as the crude thymic extract, was ineffective in decreasing DNA synthesis in non-lymphoid target cells. The I fraction was further purified by Sephadex G50 filtration and DEAE Sephadex chromatography. The active molecule seemed to be a heat resistant basic peptide probably bound to a ribonucleotide moiety.

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The effects of certain immunity systemic advuvants, PHA, and human gamma globulin on the thymic cortex of mice: a light and electron microscope study.

Thymus of (C57Bl/6 x DBA/2) F1 mice was examined histologically, histochemically and ultrastructurally, seven days after intravenous injection of BCG, pertussis vaccine, lipopolysaccharide or human gamma globulin, or intraperitoneal injection of complete or incomplete Freund's adjuvants or of phytohemagglutinin. Only BCG induced a marked increase of the secretory activity of the thymic epithelium at all histological sites (cortex, corticomedullary junction and medullar). Only with this adjuvant was the epithelial hyperplasia associated with marked mitotic activity and high percentage of cells with cytoplasmic pyroninophilia among cortical lymphoid cells. The other substances tested produced different changes in the thymic epithelial cells according to the histologic zones. These results suggest that the epithelial cells of the cortex, the corticomedullary junction and the medulla respond differently to the agents tested and that the action of these substances upon thymus-dependent lymphoid cells may be indirect perhaps involving factors secreted by the epithelial cells.

Adjuvants, Immunologic↗

Lymphocyte-macrophage interactions in BCG-treated mice.

Fresh living Bacillus Calmette-Guérin (BCG), injected i.v. into (C57Bl/6xDBA/2)Fl mice, activated peritoneal macrophages rendering them highly cytotoxic for tumor cells in vitro. This cytotoxic activity was already maximal 14 days after injection of 1 mg of BCG and remained stable when 3 or 5 mg of BCG were given. At the same time spleen cells of the BCG-treated mice showed strongly depressed responses to the T-cell mitogens, PHA and Con A, irrespective of the dose of BCG injected. The inhibitory effect was shown to be mediated by suppressor cells which had characteristics of macrophages since they could be removed by carbonyl iron and magnet treatment and were adherent to plastic. In contrast to it was observed after injection of 1 mg of BCG, these suppressor cells alone did not account for the depression of T-cell responses induced by higher doses of BCG. Nylon-nonadherent cell populations obtained from spleen cells treated with 3 or 5 mg BCG partially retained the inhibitory activity suggesting that suppressor T cells were also induced after injection of high doses of BCG.

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In vivo and in vitro macrophage activation by systemic adjuvants.

Six systemic adjuvants of immunity were tested for their ability to induce macrophage activation. Four of them: living BCG, hydrosoluble extracts from BCG (HIU II) and from M.smegmatis (IPM), and lipopolysaccharide from E.coli (LPS), when administered to normal mice render macrophages non-specifically cytotoxic for tumor cells in vitro. The intensity of this phenomenon varied according to the route and time of adjuvant administration. In contrast, lentinan extracted from Lentinus edodes, and levamisole which is a synthetic chemical compound, depressed macrophage cytotoxic potential. BCG, IPM and LPS were shown to have a direct action on macrophages. After in vitro exposure to these agents, the cytotoxic potential of normal macrophages was greatly increased. Levamisole was unable to stimulate this macrophage function directly in vitro. On the other hand, such a macrophage activation has been induced in vitro when normal macrophages were cultivated in the presence of MIF coming from the supernatant of human lymphoblastoid cell lines.

Adjuvants, Immunologic↗

Nonspecific macrophage activation by systemic adjuvants. Evaluation by lysosomal enzyme and in vitro tumoricidal activities.

Six systemic adjuvants: living bacillus Calmette-Guérin (BCG), hydrosoluble extracts from BCG and from Mycobacterium smegmatis, bacterial lipopolysaccharide, lentinan and levamisole, have been tested for their ability to induce macrophage activation in mice. The first four adjuvants mentioned increase phosphatase activity of peritoneal macrophages and make them nonspecifically cytotoxic for tumor cells in vitro. The intensity of these phenomena vary with route and time of administration. In contrast, lentinan and levamisole depress both these macrophage activities. Living BCG, extracts from BCG and from M. smegmatis, and the lipopolysaccharide increase the cytotoxic potential of normal macrophages in vitro, suggesting that these agents may exert a direct action on macrophages. Levamisole did not activate normal macrophages in vitro. The existence of a correlation between the capacity of adjuvants to stimulate macrophage tumoricidal activity and their efficiency in active cancer immunotherapy is discussed.

Acid Phosphatase↗

Further purification of the lymphocyte inhibiting extract from the thymus.

A crude thymic extract, demonstrated to possess both immunosuppressive activity on T lymphocytes in vivo, and inhibitory action on DNA synthesis in T lymphocytes in vitro, has been purified by ultra-filtration and ion exchange chromatography procedures. The immunosuppressive activity was found to be associated with a high molecular weight fraction (greater than 50,000 daltons), devoid of immunosuppressive properties, a basic peptide has been isolated which retains the in vitro inhibitory activity on DNA synthesis.

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The immunoblast.

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