Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome P450 2A6 and the body status of iron stores in adult Thai males and females

The relationships between catalytic activity of cytochrome P450 2A6 (CYP2A6), polymorphism of CYP2A6 gene, gender and levels of body iron stores were analysed in a sample group of 202 apparently healthy Thais, aged 1947 years. Eleven individuals were found to have high activity of CYP2A6, judged by the relatively large amounts (11.2-14.6 mg) of 7-hydroyxcoumarin (7-OHC) excreted 3 h following administration of 15 mg of coumarin. Ten individuals, however, did not excrete any 7-OHC. Of these 10, four were found to have no CYP2A6 gene (whole gene deletion; CYP2A6*4 allele). The frequency of the CYP2A6 alleles; *1A, *1B and *4 in the whole sample group was 52, 40 and 8% while the frequency of the CYP2A6 gene types; *1A/* 1A, *1A/* 1B, *1B/* 1B, *1A/* 4, *1BI* 4, *4/* 4 was 29, 41, 16, 7, 5 and 2%. Subjects having CYP2A6* 1A/* 1B gene-type group were found to have higher rates of coumarin 7-hydroxylation compared with those of the CYP2A6* 1B/* 1B and CYP2A6* 1A/* 4 gene types. The inter-individual variability in CYP2A6 catalytic activity was therefore attributed in part to the CYP2A6 genetic polymorphism. Variation in CYP2A6 activity in this sample group was not associated with gender but, interestingly, it did show an inverse association with plasma ferritin; an indicator of body iron stores. Higher rates of coumarin 7-hydroxylation were found in individuals with low body iron stores (plasma ferritin < 20 μg/l) compared with subjects having normal body iron store status. Subjects (n = 16) with iron overload (plasma ferritin > 300 mug/l) also tended to have elevated rates of coumarin 7-hydroxylation. These results suggest an increased CYP2A6 expression in subjects who have excessive body iron stores. Further investigations into the underlying factors that may lead to increased expression of CYP2A6 in association with abnormal body iron stores are currently in progress in our laboratory. Pharmacogenetics 12:241-249 (C) 2002 Lippincott Williams Wilkins.

Communities of the postindustrial city

The authors discern the community structure of the postindustrial city, with reference to Australia. They focus empirically on three major types of Australian urban center: urban regions. metropolitan areas that are not part of urban regions, and other major cities. These three account for almost three-quarters of the Australian population. The authors draw on a conceptualization formulated by Marcuse and van Kempen to guide the analysis, with a combination of cluster analysis and discriminant analysis being applied to aggregate (essentially census) data to identify the communities. Nine major Australian urban communities are identified-four are affluent. four are disadvantaged. and one is a working-class community. The communities found, however, differed greatly from those cited in the Marcuse and van Kempen schema.

Spondylostrobus F. Mueller: operculate fruits of an extinct dicotyledon from the mid-Tertiary of Australia

Spondylostrobus F. Mueller, which accommodates operculate fruit-stones reported only from the mid-Tertiary of Australia, is redefined on the basis of type and other specimens of the type species, S. smythii F. Mueller, and of specimens included in S. rozefeldsii sp. nov. The globose to ellipsoidal fruits have 3-6 locules symmetrically disposed around a massive fibrous axis. Each locule has a single anatropous ovule, axile placentation, and a dorsal germination operculum that extends from near the base to the apex. In possessing these characters Spondylostrobus more closely resembles operculate fruits within the tribe Spondiadeae (Anacardiaceae) than operculate fruits of other dicotyledonous families. Spondylostrobus has widespread distribution in Oligocene-Miocene sediments of eastern Australia. At many localities it is associated with fruit-stones having affinities with extant taxa that now occur in rainforests, monsoonal forests, and fringing communities of northern Australia. (C) 2002 Elsevier Science B.V. All rights reserved.

Relative importance of female-specific and non-female-specific effects on variation in iron stores between women

Women have lower iron stores than men because of iron loss during their reproductive years. However, variation between women could result from differences in iron loss, aspects of iron homeostasis common to men and women, or a combination of both. We compared the effects of age, menopause, menstrual blood loss and the number of pregnancies (sex-specific factors), and the effects of genetic variation, on markers of iron stores. We assessed how much the same genes or other familial factors influence iron status in both men and women. Data from 2039 female twins who participated in studies of reproductive health and iron status were used to estimate the proportions of variation that could be ascribed to genes, environment and measured factors. Significant effects of age, menopausal status and magnitude of menstrual blood loss were demonstrated, accounting for up to 18% of variance in serum ferritin in this sample, but number of children had no significant effect. Genetic effects were more than twice as great as sex-specific effects. The within-pair similarity of ferritin values in dizygotic female twin pairs was greater than for dizygotic opposite-sex pairs, but this difference was not quite significant, consistent with a minor role for sex-specific factors; and the opposite-sex within-pair differences did not diminish significantly with age. We conclude that the contribution of genetic differences between women to variation in iron stores outweighs the comparatively small effects of interindividual variation in iron loss through variation in menstruation and number of pregnancies.