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Biomedical subjects

M M Dale

Publications and source records attributed to M M Dale.

48 records · Page 3Linked to original sources

Comparison of antigenicity of hepatoma cells, normal liver cells, foetal liver cells and chemically damaged liver cells in guinea-pigs immunized with hepatomata using the macrophage migration inhibition test.

The macrophage migration inhibition test has been used to study the immune responses of guinea-pigs immunized with injections of whole cells of both an allogeneic and a syngeneic hepatoma grown as established cell lines in tissue culture.A clear dose-response relationship between tumour cell concentration and migration inhibition was seen in immunized animals and no significant migration inhibition was seen in control animals. There was no cross reaction between the two tumours used. There was no cross reaction between whole isolated normal liver cells and tumour cells, or between foetal liver cells and tumour cells. Whole isolated liver cells from carbon tetrachloride damaged livers caused some degree of migration inhibition in both normal and immunized guinea-pigs but, taking this into account, they did not appear to cross react with hepatoma cells.

Animals↗

The induction of tumours in the guinea-pig with methylcholanthrene and diethylnitrosamine and their propagation in vivo and in vitro.

Tumour induction with diethylnitrosamine (DEN) and methylcholanthrene (MCA) has been studied in 3 strains of guinea-pig. A DEN concentration of 80 μg/ml drinking water daily proved too toxic but reasonable survival was obtained with 20 μg/ml 3 times per week in Hartley guinea-pigs and a local inbred strain. Heston Strain 13 guinea-pigs were particularly susceptible to the toxic effects of the diethylnitrosamine. In all3strains, 100% of the animals which survived the early toxic effects subsequently developed hepatomata, the mean time being 15 months. Methylcholanthrene was less toxic but more erratic as a carcinogen, the incidence of tumours in Hartley guinea-pigs varying from 18 to 100% in different experiments, the mean time of tumour development being 10 months.Three transplantable hepatomata and 3 transplantable sarcomata have been developed. The hepatomata are all predominantly hepatocellular carcinomata and the sarcomata comprise two liposarcomata and a fibrosarcoma. Successful shortterm primary cultures of hepatomata, sarcomata and of normal liver tissues have been accomplished. Established cell lines in tissue culture have been developed from one cholangiocarcinoma from an outbred guinea-pig and one transplanted hepatocellular carcinoma from an inbred guinea-pig.

Animals↗

The Schultz-Dale response of the longitudinal muscle strip preparation of guinea-pig ileum.

1. The mast-cell distribution in the various layers of the ileum has been described.2. Histamine-content, anaphylactic histamine-release and the anaphylactic dose-response curve of the full-thickness ileum and of the longitudinal muscle strip have been measured and compared.3. Tetrodotoxin 10(-7) g/ml had no obvious effect on the anaphylactic dose-response curve of either preparation. This suggests that the plexus is not of any great importance in the Schultz-Dale reaction.4. Exposure of the longitudinal muscle strip to octylamine 10(-3) g/ml for 1 min reduced the mast cell content by 95-100%. After this treatment the dose-response curve to antigen was eliminated, although the muscle still responded to small doses of histamine and to anaphylactic mediators. Pretreatment of antibody with octylamine did not impair passive sensitization and subsequent response to antigenic challenge. This suggests that the classical Schultz-Dale reaction in the strip is mediated mainly by mast cells, and possibly other cells, and is probably not due to a direct effect of the antigen-antibody reaction on the smooth muscle.5. The typical three-phase anaphylactic response (quick contraction, quick relaxation, slow contraction) of full-thickness ileum is discussed and compared with the predominantly two-phase response of the longitudinal muscle strip. No evidence was found for the release of a relaxation-factor. It is suggested that the initial fast phase may be due to mediators released from mast cells among the longitudinal muscle fibres, and the sustained contraction to a second wave of mediators reaching the longitudinal muscle from deeper layers of the ileum.

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