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Biomedical subjects

G Lespinats

Publications and source records attributed to G Lespinats.

At least 37 records · Page 2Linked to original sources
PubMed1982

Decrease in tumour growth by injections of histamine or serotonin in fibrosarcoma-bearing mice: influence of H1 and H2 histamine receptors.

C3H and C57 BL/6 mice carrying methylcholanthrene-induced fibrosarcomas were injected i.p. daily with histamine, metiamide (anti-histamine type-2 receptor), histamine + metiamide, mepyramine (anti-histamine type-1 receptor), serotonin and methysergide (anti-serotonin). Inhibition of tumour growth and lengthened survival were observed with histamine and histamine + metiamide. The best results (both on tumour growth and survival) were obtained with serotonin. Survival was increased by metiamide and decreased by mepyramine and methysergide. In histamine-treated and in serotonin-treated mice, histological studies of the tumours showed large and numerous foci of haemorrhagic necrosis. Stimulation of histamine type-1 or serotonin receptors and inhibition of histamine type-2 receptors play a beneficial role in the host's defence against tumours.

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PubMed1982

Peptidoglycans extracted from gram-positive bacteria: expression of antitumor activity according to peptide structure and route of injection.

The antitumor effect of peptidoglycans of various structures extracted from different gram-positive bacteria was studied, on chemically induced fibrosarcomas, in C3H/He, C57BL/6, and (C57BL/6 X C3H/He)F1 mice. When given sc admixed with tumor cells, only some peptidoglycans (those extracted from Bacillus megaterium and Staphylococcus aureus) enhanced tumor resistance in syngeneic and semiallogeneic hosts, whereas other peptidoglycans (those extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) possessed no antitumor effect. When tumor cells were given ip, administration of peptidoglycans by the same route was either without effect on tumor growth or it induced tumor enhancement. Enhancement could be observed with all of the peptidoglycans tested. The antitumor effect when given sc and the ability to stimulate the proliferation of B-lymphocytes were shared by the same two peptidoglycans, while the other two peptidoglycans were devoid of both activities. It appears that these biological activities depend on the structure of the peptide moiety of peptidoglycans and that mitogenic and antitumor responses are stimulated by similar structures.

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PubMed1981

Adoptive transfer of immunity induced by semi-allogeneic hybrid cells, against a murine fibrosarcoma.

Semi-allogeneic somatic hybrid cells derived from the fusion of a C57BL/6 fibrosarcoma (MCB6-1) and A9 cells (C3H origin) were used to immunize C57BL/6 mice against the parental tumor cells. These hybrid cells expressed H-2 histocompatibility antigen of both parental cells (H-2b and H-2k), and failed to produce tumors in normal C57BL/6 mice. A single i.p. injection of hybrid cells induced anti-tumor immunity which could be transferred to normal C57BL/6 recipient mice by immune spleen or peritoneal cells; the efficient cells were T cells, as this activity was completely abrogated by treatment with anti-Thy-1-2 antiserum and complement. Among immune splenic T cells, only the light-density T cells, obtained after fractionation on Percoll gradient, were effective in the transfer of immunity. Immunity induced by the hybrid cells was specific for MCB6-1 parental tumor cells. This immunity could be transferred during two brief periods, 7 to 12 days, and 40 to 50 days, after hybrid cell injection; there appeared to be an intermediate period, 12 to 40 days after immunization, during which no immunity could be transferred. These results suggest a suppressive mechanism implicated during hybrid cell immunization and interacting with the anti-tumor immune response.

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PubMed1981

The influence of intraperitoneal injections of histamine on tumour growth in fibrosarcoma-bearing mice.

Twenty C57BL/6 male and 20 C3H female mice carrying a methyl cholanthrene-induced fibrosarcoma received, daily, intraperitoneal injections of histamine dihydrochloride (1.8 mg or 6 mg histamine base/mouse). In all histamine-treated C57BL/6 mice, tumour growth was significantly slower than in control mice until day 18. Thereafter, the tumour growth rate of treated compared to control mice was accelerated. In 10 out of 20 C3H mice, tumour growth was significantly slower until day 25; in histamine responsive C3H mice, histological studies showed numerous and large loci of acute haemorrhagic necrosis in the tumours.

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PubMed1981

Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG.

The i.v. injection of high doses (3 mg) of BCG into C3H mice bearing a transplantable 3-methylcholanthrene-induced fibrosarcoma caused the regression of a significant proportion. This effect was most evident when the BCG was injected on the day of the graft, or 7 days later. The injection of this agent either 14 days before the graft, or in low doses (0.1 or 0.5 mg), or directly into the tumour (i.t.) only prolonged the survival of the animals. Spleen cells from systemic high-dose BCG-treated mice were found to exert a strong nonspecific cytostatic effect in vitro that was not an artefact of the test conditions, and was not expressed by cells from low-dose animals. The cytostatic effect was shown to be caused by cells with the characteristics of macrophages, i.e. they were strongly adherent, unaffected by treatment with anti-Thy 1.2 + C', radioresistant but heat-sensitive, and were detected in BCG-treated "B" mice. The spleens of high-dose BCG-treated mice also contained suppressor cells that were capable of inhibiting the in vitro reactivity of normal T cells to PHA. Like the cytostatic effect, this suppressor activity was not detected in low-dose mice, and the cells responsible had the properties of macrophages; the effect was lost after the removal of adherent cells by sequential exposure to plastic and colloidal iron, but was conserved after treatment with anti-Thy 1.2 + C'. T-cell-deprived animals, such as "B" or nude mice, also developed suppressor-cell activity when treated with systemic high-dose BCG. Close parallels became evident between the in vivo anti-tumour activity of BCG, the in vitro cytostatic effect, and the suppressor-cell activity. We here discuss the possible role of suppressor cells in the mechanism of action of this agent.

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PubMed1981

Increased tissue histamine in tumour-bearing mice and rats.

Tissue histamine levels were studied in C3H and C57BL/6 mice bearing a methylcholanthrene-induced fibrosarcoma, in Wag rats bearing an aflatoxin B1-induced hepatoma, and in Commentry rats bearing a grafted hepatoma. Histamine levels were significantly higher (1.5 to 3 fold) in the tumour-bearing animals for ventral and dorsal skin, skeletal muscle and stomach fundus. Total histamine content was increased in the spleen. In C3H mice with McC3-1 fibrosarcoma, the excision of the tumour or its partial regression by intratumoral injections of corynebacterium parvum induced a reversion to normal values. The tumour thus appears responsible for the increased histamine levels in tissues distant from the tumour.

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PubMed1981

Adoption of tumor immunity: role of the major histocompatibility complex.

T cells from spleens of mice immunized against a chemically induced tumor were able, when transferred to normal syngeneic mice together with tumor cells, to protect adoptively against tumor growth. The inability of such cells to identically protect pangenic nude mice and F1 hybrid mice, and the incompetence of T cells alone in the in vitro tests indicated that the T cells by themselves were unable to kill the tumor cells. We hypothesized that the protection transmitted by spleen T cells results from an interaction with the recipient mouse and that this interaction is controlled by the major histocompatibility complex (MHC). Analysis of the lack of protection at the level of the MHC subregion demonstrated that in the transfer of immune spleen T cells from parent mice to F1 recipient mice, an identity of the KIA subregion permitted a complete transfer of protection. In the transfer of immune spleen T cells from F1 mice to parent recipients, a semi-identity of the KIA subregion was sufficient but a complete identity of the H2D subregion was necessary. The use of such a model, requiring the transfer of parental cells to F1 hybrid mice, necessitated the analysis of the possible role of the hybrid resistance gene. We have demonstrated the absence of correlation between the hybrid resistance and the adoptive protection. At the present stage of this work, the adoptive neutralization test allows us to conclude that the immunologic rejection of a chemically induced tumor is the result of interaction between 2 cells, a T cell and a radioresistant non-T cell.

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PubMed1980

NK activity in carrageenan-treated mice.

NK activity was determined by measuring 51chromium released from Yac-1 target cells incubated with spleen cells from normal or carrageenan (Car)-treated mice. Intraperitoneal administration of a single dose of i-Car (3 mg) provoked splenomegaly in mice. This splenomegaly accompanied during the first days (2-3), a marked increase of NK activity, then a decrease of this activity at day 8-9. It was returned to normal level at day 30. The modulation of NK activity in Car-treated mice is not due to the variation of the number of NK cells, since the frequency of target-binding cells (TBC) was not modified. The increase in NK activity during the first days may be due to the presence of interferon induced by carrageenan. Concomitant injection of an anti-mouse interferon globulin with carrageenan abolished the boosting of NK activity. NK activity of spleen cells from Car-treated mice at day 8 could not be stimulated by interferon in vitro as it could with the normal spleen cells. No decrease of NK activity was observed in Car-treated mice at day 8, when indomethacin was administered. Hence the decrease of this activity in Car-8 mice might be partially due to the alteration of NK effector cells induced by prostaglandins.

Animals↗
PubMed1979

Immunity to a 3-methylcholanthrene-induced fibrosarcoma in the C57BL/6 mouse: in vivo analysis by the adoptive tumor neutralization test.

Analyses of the adoptive tumor neutralization test (modified Winn test) in C57BL/6 mice made immune to a 3-methylcholantheene-induced fibrosarcoma showed that the reaction was mediated by a thymus-derived lymphocyte, it was tumor-specific, and the resistance of the immunized donor mouse to the challenge was strongly correlated with the protection of the recipient mouse. Proliferation of immune cells and close contact between tumor cells and immune T-cells were required. The hypothesis of a participation of the recipient in the reaction was considered because of the lack of adoptive protection of pangenic nude mice.

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PubMed1979

Immunosuppressive activity of Fusarium toxins. Effects on antibody synthesis and skin grafts of crude extracts, T2-toxin and diacetoxyscirpenol.

The inhibitory effect of crude Fusarium poae extracts, T2-toxin and diacetoxyscirpenol on synthesis of antibody to sheep red blood cells was investigated, as well as the effect of T2-toxin on skin graft rejection. Fusarium crude extracts, T2-toxin and diacetoxyscirpenol cause a significant reduction in thymus weight and inhibit responsiveness to sheep red blood cells. The effect on antibody synthesis was critically dependent on the drug doses used. The effect of an immunosuppressive dose of T2-toxin disappeared within 6 days after the end of the treatment. The administration of T2-toxin subsequent to immunization stops antibody synthesis. T2-toxin significantly prolongs the period required for skin graft rejection.

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PubMed1978

Antibody production by spleen cells of mice bearing MCA-induced tumours: search for suppressor cells.

The antibody response to sheep red blood cells of spleen cells from mice bearing a methylcholanthrene (MCA)-induced tumour was measured with the local hemolysis technique, after in vivo or in vitro immunization. The in vivo data varied according to the stage of tumour growth and were related to the splenomegaly developing during the tumour growth process. During the first 10--15 days after tumour grafting, the total number of plaque-forming cells in the spleen increase in proportion to the spleen growth and thereafter remained relatively constant although the splenomegaly still progressed. Experiments performed in vitro were used to test the antibody response of mixtures of cells from normal mice and syngeneic tumour-bearing animals. In most cases, no suppression of antibody production, due to cells from tumour-bearing hosts, could be detected. The results suggest that those cells, which suppress cell-mediated immune reactions, previously found in the spleen of animals bearing the MCA-induced tumour, do not suppress antibody production.

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PubMed1977

Cytostatic effect of spleen cells of tumor-bearing mice on syngenetic tumor cells.

Spleen cell suspensions of methylcholanthrene-induced tumor-bearing mice were tested for their ability to inhibit tumor growth in vitro. The level of cytostasis was correlated with tumor growth and disappeared rapidly after surgical removal of the tumor. Pretreatment by anti-Thy 1-2 antiserum and complement, or by carbonyl iron and a magnet, showed that adherent, non-T-cells were the main effector cells of the cytostatic antitumor effect. Thymus cells suspensions from tubor-bearing mice were not effective in inhibiting tumor growth. This cytostatic effect was not tumor specific, inasmuch as the same spleen cell suspension inhibited growth of tumor cells of different origin.

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PubMed1976

Evidence for splenic suppressor cells in C3H/He, T-cell-deprived C3H/He, and nude mice bearing a 3-methylcholanthrene-induced fibrosarcoma.

Suppressor cells were demonstrated in the spleens of C3H/He mice carrying 3-methylcholantrene-induced fibrosarcomas. These cells inhibited the in vitro reactivity of normal lymphocytes to T- and B-cell mitogens. They disappeared within a few days after the tumor was surgically removed. Pretreatment of spleen cells (ScC) from tumor-bearing (TB) mice with either iron and a nagnet, antiserum against Thy 1.2 antigen plus complement, or antiserum against immunoglobulin plus complement demonstrated that the suppressor cells were adherent, non-T-cells bearing immunoglobulin at their surfaces. The suppressive effect could still be demonstrated by addition of SpC from TB mice 24 or 48 hours after phytohemagglutinin stimulation of normal SpC, SpC from TB C3H/He mice inhibited mitogen-induced stimulation of both C3H/He and DBA/2 lymphocytes. In T-cell-deprived TB C3H/He mice, suppressor cells were also observed and had the same characteristics as those in non-T-cell-deprived mice. In nude mice, however, although suppressor cells were active, they were not adherent and did not bear immunoglobulin at their surfaces. The existence of these suppressor cells may be one reason why the immune system of TB animals is unable to reject the tumor.

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