Biomedical subjects
D G Lindsay
Publications and source records attributed to D G Lindsay.
Zeranol--a 'nature-identical' oestrogen?
The use of implants of zeranol (alpha-zearalanol), a widely-used anabolic growth promoter, in food animals results in very low residues of this compound in the edible tissues. In comparison, residues of myco-oestrogens--specifically the beta-resorcylic acid lactones (RALs) such as zearalenone and its metabolites--commonly found as contaminants of cereals are much greater. Zeranol, the RALs and their metabolites are all closely related chemically, sterically and biologically. The biological effects of these compounds on reproduction, oestrogenicity, teratogenicity, genotoxicity and carcinogenicity are compared. No toxicological effects have been reported that cannot be attributed to the oestrogenic character of these molecules. In comparison with oestradiol, zeranol and the related myco-oestrogens are 100-1000 times less active hormonally. It is concluded that a likely no-observed-effect level (NOEL) for these compounds will be of the order of 0.05-0.1 mg/kg body weight/day. This would result in a safety margin greater than 500-fold between the expected dietary exposure to these compounds (considered together) and the likely NOEL. On the basis of exposure to zeranol alone, this margin of safety would increase to more than 35,000.
Duplicate diet study on fishing communities in the United Kingdom: mercury exposure in a "critical group".
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Reorganization of the UK total diet study for monitoring minor constituents of food.
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Receptor-binding region of insulin.
X-ray analysis, circular dichroism, receptor binding and biological potencies of chemically modified insulins suggest that the conformation of the insulin molecule is critical to the formation of both the zinc insulin hexamer and the insulin-receptor complex. Results are consistent with an insulin receptor-binding region including many of the hydrophobic residues important to dimerisation in addition to more polar surface residues. There is a further possibility of formation of an antiparallel sheet structure between the insulin and receptor molecules in the complex similar to that between monomers in the insulin dimer.
Carbamyl- and methylthiocarbamylinsulins.
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X-linked mental retardation without physical abnormality (Renpenning's syndrome) in sibs in an institution.
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The acetylation of insulin.
The acetylation of the free amino groups of insulin was studied by reaction of the hormone with N-hydroxysuccinimide acetate at pH6.9 and 8.5. The products formed were separated by chromatography on DEAE-Sephadex and were characterized by isoelectric focusing, by end-group analysis, by the incorporation of [(3)H]acetyl groups in the molecule, and by treatment with trypsin that had been treated with 1-chloro-4-phenyl-3-toluene-p-sulphonamidobutan-2-one (;tosylphenylalanyl chloromethyl ketone'). Three monosubstituted products, two disubstituted products and one trisubstituted derivative were prepared. The alpha-amino groups of the terminal residues and the in-amino group of the lysine-B29 were the sites of reaction. Acetylation of any of the free amino groups did not affect the biological activity of insulin. It was demonstrated, however, that substitution at the glycine-A1 amino group by the larger residues, acetoacetyl or thiazolidinecarbonyl, produced a decrease in biological activity. Modification of the lysine-B29 or phenylalanine-B1 amino groups with these larger reagents did not affect the biological activity. Modification of the phenylalanine-B1 amino group by any of the three substituents resulted in a large decrease in the affinity of insulin for anti-insulin antibodies raised in the guinea pig. Modification of the other two amino groups did not affect the reaction with antibody. These observations are correlated with the tertiary structure of insulin.
Synthesis of peptides related to bradykinin.
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Lipid compsition on comedones compared with that of human skin surface in acne patients.
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Monosubstituted 2,2-dimethyl-3-formyl-L-thiazolidine-4-carbonyl-insulins.
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Acetoacetylation of insulin.
Insulin was treated with diketen at pH6.9. The reaction mixture was resolved into four components by DEAE-Sephadex chromatography. The first component was unchanged insulin. The second and third components were shown by end-group analysis to be substituted on phenylalanine B-1 and glycine A-1 respectively. The fourth component was disubstituted on both phenylalanine B-1 and glycine A-1. The in-amino group of lysine B-29 was not involved in the reaction at low reagent concentrations. The purity of these derivatives was checked by their electrophoretic behaviour and by measurement of the rate of their reaction with trinitrobenzenesulphonic acid. The hormonal activity of the derivatives was determined. The effect of the modifications on the hormonal activity and the tertiary structure of insulin is discussed.
Estimation of the dietary intake of chemicals in food.
Methods for estimating the exposure of individuals to chemical substances present in the diet require information to be obtained about the patterns of food consumption in a community as well as the concentration of these chemicals in the diet. Methods of estimating food intakes using food diaries/weighed intake studies, dietary recall studies, food frequency and food disappearance methods are described. Their use, together with calculations derived from the data they provide are described to estimate normal and atypical food consumption patterns. The methods which have been used to estimate the exposure to existing chemicals in food are briefly reviewed and include total diet studies, selective studies on individual foods and duplicate portion studies. These methods are inappropriate for estimating the prospective intake of a chemical in food and the ways in which this issue may be approached, both nationally and internationally, are described with particular reference to the intakes of pesticide residues and food additives.