PubMed Health⌕ Search

Biomedical subjects

N Kiger

Publications and source records attributed to N Kiger.

12 recordsLinked to original sources
PubMed1979

Restoration of impaired immune functions of aged animals by chronic bestatin treatment.

An attempt to correct the state of immunodeficiency in old age was made by repeatedly injecting a chemically defined immunostimulating agent, bestatin, to 16 month old (C57Bl/6 x BALB/c) F1 mice. Aged mice were found to have depressed T-cell and B-cell responses but increased ADCC activity. Weekly injections of bestatin over a period of 6 months resulted in varying effects depending on the dose administered. Small doses (10 microgram per injection) were more effective in restoring humoral responses to SRBC rather than delayed-type hypersensitivity reactions, whereas large doses (100 microgram per injection) acted in the opposite way. Macrophage activation was only obtained after the administration of the high doses of bestatin. Continuous treatment with bestatin did not prevent the appearance of suppressor cells induced by ageing. It led to a significant reduction of ADCC activity in aged animals near to the base line value of young animals. Animals were examined for the presence of spontaneous tumours from the end of the treatment until the age of 28 months. A significant reduction of spontaneous tumour incidence was observed in mice given repeated injections of 100 microgram bestatin when compared to untreated aged mice and to mice given the low doses of bestatin.

Aging↗
PubMed1978

Pharmacologic factors and manipulation of immunity systemic adjuvants in cancer therapy.

Because of the experimental and clinical studies which have been extensively conducted with bacillus Calmette-Guérin (BCG) as a systemic adjuvant in cancer immunotherapy, we have analyzed the main factors and conditions which determine its beneficial action and have underlined some of these (eg, the dose factor which controls the amplification of suppressor cells which is probably responsible for failures and even the possible tumor-enhancing effect of immunotherapy). Knowing those factors and conditions, we have been able to establish a systematic immunopharmacologic study of systemic immunity adjuvants, which has resulted in the discovery of agents whose actions are more rapid than that of BCG on one or a few populations of cells involved in immunity and which, unlike BCG, do not induce suppressor cell amplification. This amplification may explain the difference in the results obtained with this mycobacterium in various clinical immunotherapy trials in which it was applied differently. It is proposed to combine these mono- or pauc-functional adjuvants in order to try to obtain all of the beneficial effects of BCG without the amplification of suppressor cells.

Adjuvants, Immunologic↗
PubMed1978

Effects of Bacillus Calmette-Guérin and levamisole on immune responses in young adult and age-immunodepressed mice.

The immunomodulating effects of bacillus Calmette-Guérin (BCG) and levamisole were tested in young adult mice after a single administration and in 12-month-old mice after continuous administration. In young mice, BCG was shown to activate macrophages, to potentiate antibody responses and delayed hypersensitivity reaction, to increase antibody-dependent cell-mediated cytotoxicity, and to induce nonspecific suppressor cells. Levamisole was not able to modify any of these immune responses in young mice. The action of these adjuvants differed markedly when tested in age-immunodepressed mice. BCG was found to be strongly immunosuppressive on antibody formation and induced suppressor cell activity in the spleen. Moreover, the survival of immunodepressed mice continuously treated with BCG was shortened in comparison to untreated aged mice. In contrast, levamisole acted as an immunorestoring agent because it strongly stimulated the antibody response compared to aged controls and did not induce suppressor cell population. The survival of levamisole-treated mice was prolonged when compared to untreated aged mice. When the surviving mice were killed and autopsied at the age of 24 months, the incidence of spontaneous tumors was significantly lower in the group of mice treated by levamisole.

Age Factors↗
PubMed1977

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.

Animals↗
PubMed1977

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.

Animals↗
PubMed1975

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.

Animals↗