Showing papers by "Arno G. Motulsky published in 1993"

The glutathione S-transferase μ polymorphism as a marker for susceptibility to lung carcinoma

Abstract: Glutathione S-transferase (GST) enzymes detoxify carcinogens in tobacco smoke. Interindividual variation in GST function may be related to differences in risk for smoking-related cancer. Leukocytes from 50% of Caucasians lack GST activity toward trans-stilbene oxide (TSO), due to a deletion of the gene for the GST-µ enzyme. Presence of GST-TSO activity in leukocytes has been associated with low risk for lung cancer among cigarette smokers. We sought to determine whether GST activity in lung tissue is determined by the same gene polymorphism and whether it is associated with risk for lung cancer. Subjects were cigarette smokers, identified at the time of lung resection or autopsy in Seattle hospitals. Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-µ activity with TSO, for the presence of the GST-µ gene product with an immunological assay, and for the GST-µ gene with Southern blotting. Mailed questionnaires were used to collect information on subjects9 smoking histories and exposures which might alter enzyme activity. Interindividual results from the three assays correlated well. Smokers with high GST-TSO enzyme activity present in their lung tissue had a lower risk for lung carcinoma than did smokers with no or low activity (relative risk = 0.30; 95% confidence interval, 0.11–0.79), as did smokers with GST-µ antigen identified in lung tissue versus those with no antigen (relative risk = 0.30; 95% confidence interval, 0.11–0.79). Smokers with both maternal and paternal copies of GST-µ DNA (n = 7) had a lower cancer risk than smokers lacking GST-µ DNA (n = 30; relative risk = 0.35; 95% confidence interval, 0.06–2.10). High GST-µ activity appeared to be associated with a greater decrease in lung cancer risk among 38 heavy cigarette smokers (relative risk = 0.15; 95% confidence interval, 0.03–0.64) than among 38 light smokers (relative risk = 0.61; 95% confidence interval, 0.14–2.60). Presence or absence and number of copies of the GST-µ gene appear to determine activity of the GST-µ enzyme in lung. Smokers with the GST-µ enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme.

Host and environmental effects on plasma apolipoprotein B.

Abstract: In this study, levels of apo B in an unselected sample of 487 middle-aged Caucasian spouses of patients and spouses of the patients' relatives are described. In males, apo B levels increased with age until the 7th decade, then declined; apo B levels in females, which were lower than in males, increased linearly with age across the entire life-span. Height and weight, smoking, and presence of noninsulin-dependent diabetes mellitus significantly influenced age- and gender-adjusted apo B levels in this sample, whereas use of alcohol, diuretics, beta-blockers, or insulin did not. Age, gender, height, weight, smoking, and noninsulin-dependent diabetes mellitus account for 21% of the total variation in apo B levels in this sample.

Structure-function relationships in human red/green color vision

Abstract: The relationship between molecular structure of the visual pigment genes and red-green color vision was studied in 126 normal and 63 color-defective males. We found that the great majority of defects in red-green color vision are associated with the formation of 5′R-G hybrid genes (protan series), deletion of the G gene (deutan series), or the formation of 5′R-G hybrid genes (deutan series). Within these two series, however, dichromacy and trichromacy cannot always be predicted from the molecular patterns, particularly among protans. Amino acid residues in exon 5 largely determine whether a hybrid gene will be more R-like or more G-like in phenotype. We observed numerous genetic polymorphisms in the R and G pigment genes of both normal and color-defective subjects. These polymorphisms may account for some, but not all, of the observed variations in color vision phenotypes. A common Ser/Ala polymorphism at position 180 of the R pigment gene was found to be highly correlated with the bimodal distribution of Raleigh matches we observed among 50 color-normal Caucasian males.

The American Medical Association Scientific Journals 1993 Theme Issues on Molecular Genetics and Medicine: Call for Papers

Abstract: The year 1993 marks the 40th anniversary of the publication of the two short, seminal articles by Watson and Crick 1,2 on the double helix structure of DNA During these 40 years, a revolution in biology and genetics has occurred as the insights gained from this discovery have moved these fields to a new molecular level of understanding During the past decade, we have also witnessed the beginning of another revolution in medical knowledge and therapeutics as the insights and techniques of molecular biology, molecular genetics, and recombinant DNA technology have begun to have an impact on medicine These advances in what is now being called molecular medicine are having an ever increasing impact on many areas of medicine: (1) molecular diagnostic techniques are moving diagnosis from the phenotypic to the genotypic level (eg, the sweat chloride test for cystic fibrosis vs the identification of a mutation in the cystic