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.

The current status of laser applications in dentistry

A range of lasers. is now available for use in dentistry. This paper summarizes key current and emerging applications, for lasers in clinical practice. A major diagnostic application of low power lasers is the detection of caries, using fluorescence elicited from hydroxyapatite or from bacterial by-products. Laser fluorescence is an effective method for detecting and quantifying incipient occlusal and cervical,carious lesions, and with further refinement could be used in the, same manner for proximal lesions. Photoactivated dye techniques have been developed which use low power lasers to elicit a photochemical reaction, Photoactivated dye techniques' can be used to disinfect root canals, periodontal pockets, cavity preparations and sites of peri-implantitis. Using similar principles, more powerful lasers tan be used for photodynamic therapy in the treatment of malignancies of the oral mucosa. Laser-driven photochemical reactions can also be used for tooth whitening. In combination with fluoride, laser irradiation can improve the resistance of tooth structure to demineralization, and this application is of particular benefit for susceptible sites in high caries risk patients. Laser technology for caries' removal, cavity preparation and soft tissue surgery is at a high state of refinement, having had several decades of development up to the present time. Used in conjunction with or as a replacement for traditional methods, it is expected that specific laser technologies will become an essential component of contemporary dental practice over the next decade.

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER-2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC. (C) 2003 Elsevier Science Ltd. All rights reserved.

The status of hollow-bearing trees required for the conservation of arboreal marsupials in the dry sclerophyll forests of south-east Queensland, Australia

At 38 sites in the dry sclerophyll forests of south-east Queensland, Australia, hollow-bearing trees were studied to determine the effects of past forestry practices on their density, size and spatial distribution. The density of hollow-bearing trees was reduced at sites that had been altered by poisoning and ringbarking of unmerchantable trees. This was especially the case for living hollow-bearing trees that were now at densities too low to support the full range of arboreal marsupials. Although there are presently enough hollow-bearing stags (i.e., dead hollow-bearing trees) to provide additional denning and nesting opportunities, the standing life of these hollow-bearing stags is lower than the living counterparts which means denning and nesting sites may be limited in the near future. The mean diameter at breast height (DBH) of hollow-bearing stags was significantly less than that of living hollow-bearing trees. This indicated that many large hollow-bearing stags may have a shorter standing life than smaller hollow-bearing stags. Hollow-bearing trees appear to be randomly distributed throughout the forest in both silviculturally treated and untreated areas. This finding is at odds with the suggestion by some forest managers that hollow-bearing trees should have a clumped distribution in dry sclerophyll forests of south-east Queensland.

To marry or not to marry: marital status and the household division of labour

Data from an Australian national survey (1996 to 1997) are used to examine domestic labor patterns among de facto and married men and women. The results show that women spend more time on housework and do a greater proportion of housework than men. However, the patterns are most traditional among married men and women. Women in de facto relationships spend less time doing housework and do a smaller proportion of indoor activities than married women. Men in de facto relationships do a larger proportion of indoor activities and a lower proportion of outdoor tasks than married men. The data also show that couples who have cohabited prior to marriage have more egalitarian divisions of labor than those who have not cohabited prior to marriage. This article concludes by arguing that the incompleteness of the de facto relationship provides a period of relative freedom in which to negotiate more equal roles.

When group members admit to being conformist: The role of relative intragroup status in conformity self-reports

Five studies examined the hypothesis that people will strategically portray the self as being more g-roup influenced the more junior they feel within the group. Among social psychologists (Study 1), ratings of self-conformity by g-roup members were greater when the status of the participant was low than when it was high. These effects were replicated in Studies 2, 3, and 4 in which relative intragroup status was manipulated. In Study 3, the authors found junior group members described themselves as more conformist than senior members when they were addressing an ingroup audience, but when they were addressing an outgroup audience the effect disappeared. Furthermore, junior members (but not senior members) rated themselves as more conformist when they were led to believe their responses were public than when responses were private (Study 5). The discussion focuses on the strategic processes underlying low-status group members' self-reports of group influence and the functional role of conformity in groups.