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Biomedical subjects

M C Berenbaum

Publications and source records attributed to M C Berenbaum.

At least 55 records · Page 3Linked to original sources
PubMed1976

Intercellular immunological controls and modulation of cyclic AMP levels. Some doubts.

We have re-examined two sets of observations put forward to support the hypothesis that rises in cAMP levels induced by vasoactive amines and prostaglandins are involved in the intercellular control of immunological and inflammatory processes. (1) This hypothesis is said to be supported by the fact that cholera toxin, which raises cAMP levels in lymphoid tissue in vivo, is immunosuppressive. However, we found that cholera toxin inhibited antibody production only if given in doses causing gross destruction of lymphoid tissue. This sort of evidence, therefore, cannot be used to support a hypothesis about homoeostasis under physiological conditions. (2) The hypothesis is also said to be supported by the claim that vasoactive amines, prostaglandins, cholera toxin and methyl xanthines, which raise cAMP levels in cells in vitro, also inhibit the formation of haemolytic plaques by spleen cells from mice immunized with sheep red cells. However, we were unable to confirm this claim, except when the experimental conditions were such that cells were killed or other artefacts operated.

Animals↗
PubMed1975

Photodynamic destruction of human bladder carcinoma.

Eleven human bladder carcinomata of different degrees of differentiation were implanted in mice immunosuppressed by thymectomy, anti-thymocyte serum and x-rays. Seven carcinomata grew well and one poorly and 3 produced mainly fibrous nodules in the mice. Normal human bladder tissues were grown from 4 other patients. The administration of a haematoporphyrin derivative (HpD), followed 24 h later by exposure to white light, caused marked destruction of tumours but little or none of normal bladder tissues. HpD or light alone caused no damage to tumours or normal tissues. It is suggested that photodynamic therapy may be applicable in the treatment of superficial transitional cell carcinoma of the bladder.

Animals↗
PubMed1974

The growth of human tumours in immunosuppressed mice and their response to chemotherapy.

One hundred and sixteen human tumours were transplanted to thymectomized, irradiated, antilymphocyte serum-treated mice. In 12 cases the recipient mice died rapidly, presumably from infection. With the remaining 104 tumours, three-quarters grew to a varying extent, retaining the characteristic histological features of the primary tumours. Implant nodules varied widely in composition, from solid tumour and stroma to dense fibrous tissue without recognizable tumour cells. There was no relation between degree of malignancy and ability to grow, and also some benign tumours grew.In 44 cases, mice were treated with the drug or drugs most likely to be used in the patients and the effects on the implants were assessed histologically. Two tumours were largely destroyed and one showed marked metaphase arrest. Three other tumours showed lesser changes that were attributable to the drug but were of equivocal significance.There appeared to be differences in drug sensitivity between structurally different clones of the same tumour, and some tumours treated with two alkylating agents were damaged by one and not the other, suggesting that this model may have substantial discriminatory power. Assays such as this should not be used to guide treatment of the patient without prior validation. The practical and ethical difficulties of validation by clinical trial may be insurmountable, and an alternative approach to validation is proposed which does not raise these difficulties.

Animals↗
PubMed1971

The effect of cysteine on the immunosuppressive activity of busulphan, cyclophosphamide and nitrogen mustard.

The effect of cysteine on the immunosuppressive activity of three alkylating agents was tested. Cysteine strongly inhibited the ability of cyclophosphamide and nitrogen mustard to depress the direct plaque-forming cell response of mice to sheep red cells. In contrast, the activity of busulphan was usually potentiated by administration of cysteine. This throws doubt on the hypothesis that busulphan exerts its cytotoxic effects by alkylating thiol groups.

Alkylation↗
PubMed1971

Immunosuppression by platinum diamines.

Platinum diamine dichloride and tetrachloride inhibit the formation of antibody-forming cells in the mouse spleen after injection of sheep red cells. The dichloride is the more effective agent. It acts best when given 2 days after the antigen, which suggests that cells are more sensitive to its action when they are rapidly proliferating than when they are resting. Its dose-response curve is exponential, suggesting that its action is like that of an alkylating agent. Platinum ethylene diamines were relatively ineffective in this system.

Amines↗
PubMed1971

The sensitivity to chemotherapeutic agents of a rat tumour grown in immunosuppressed mice.

The rat Walker 256 tumour was grown in mice that had previously been thymectomized and treated with anti-lymphocyte serum. These rat tumour-bearing mice were used to determine the therapeutic indices of 4 anti-tumour drugs.The agent with the highest index of the four examined was 5-aziridino 2,4-dinitrobenzamide (CB1954), followed by melphalan, aniline mustard and methotrexate, in that order. This rank order is the same as that found when therapeutic indices are determined on the Walker tumour growing in the rat. In this system, therefore, drugs have been ranked correctly in effectiveness against a rat tumour by measuring their effects on the tumour when growing in an immunosuppressed xenogeneic species. The implications for testing the drug sensitivity of individual human tumours before treating the patient are discussed.

Animals↗