Linkage and Association Analysis of Radiation Damage Repair Genes XRCC3 and XRCC5 with Nevus Density in Adolescent Twins

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

Heritability of adult body height: A comparative study of twin cohorts in eight countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

Induction of metallothionein in human skin by routine exposure to sunlight: Evidence for a systemic response and enhanced induction at certain body sites

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo . Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

Body proportions in three Nigerian tribes

Prediction equations of body composition based on measurements of whole-body bioelectrical impedance analysis (BIA) have been found to be population-specific. It was hypothesised that this may be, in part, due to differences in proportional limb lengths between ethnic or racial groups. As a preliminary to a survey of body composition in urban Nigerians using BIA, the relative limb lengths of the three major tribal groups (Hausa, Yoruba and Ibo) were determined. We found small (5-9%) but significantly longer limb lengths in Nigerians compared to a Caucasian population, but no significant differences between tribes. This implies that BIA prediction equations generated in a Caucasian population are inappropriate for use in a Nigerian population.

Retinal specializations in the blue marlin: eyes designed for sensitivity to low light levels

The large eyes and well-developed visual system of billfishes suggest that vision is an important sense for the detection and interception of prey and lures. Investigations of visual abilities in these large pelagic fishes are difficult, however anatomical studies of billfish eyes and retinas allow prediction of a number of visual capabilities. From the density of ganglion cells in the blue marlin (Makaira nigricans) retina, visual acuities of less than 10 cycles per degree were derived, a surprisingly low visual resolution given the absolute size of the marlin eye. Cone photoreceptors, on the other hand, were present in high densities, resulting in a presumed summation of cones to ganglion cells at a ratio of 40:1, even in the area of best vision. The optical sensitivity of the marlin eye was high owing to the large dimensions of the cone photoreceptors. These results indicate that the marlin eye is specifically adapted to cope with the low light levels encountered during diving. Since the marlin is likely to use its vision at depth, it is suggested that this line of research could help estimate the limits of vertical distribution based on light level.

Estimation of body fatness from body mass index and bioelectrical impedance: comparison of New Zealand European, Maori and Pacific Island children

Objective: To compare percentage body fat (%BF) for a given body mass index (BMI) among New Zealand European, Maori and Pacific Island children. To develop prediction equations based on bioimpedance measurements for the estimation of fat-free mass (FFM) appropriate to children in these three ethnic groups. Design: Cross-sectional study. Purposive sampling of schoolchildren aimed at recruiting three children of each sex and ethnicity for each year of age. Double cross-validation of FFM prediction equations developed by multiple regression. Setting: Local schools in Auckland. Subjects: Healthy European, Maori and Pacific Island children (n = 172, 83 M, 89 F, mean age 9.4 +/- 2.8(s. d.), range 5 - 14 y). Measurements: Height, weight, age, sex and ethnicity were recorded. FFM was derived from measurements of total body water by deuterium dilution and resistance and reactance were measured by bioimpedance analysis. Results: For fixed BMI, the Maori and Pacific Island girls averaged 3.7% lower % BF than European girls. For boys a similar relation was not found since BMI did not significantly influence % BF of European boys ( P = 0.18). Based on bioimpedance measurements a single prediction equation was developed for all children: FFM (kg) = 0.622 height (cm)(2)/ resistance +0.234 weight (kg)+1.166, R-2 = 0.96, s. e. e. = 2.44 kg. Ethnicity, age and sex were not significant predictors. Conclusions: A robust equation for estimation of FFM in New Zealand European, Maori and Pacific Island children in the 5 - 14 y age range that is more suitable than BMI for the determination of body fatness in field studies has been developed. Sponsorship: Maurice and Phyllis Paykel Trust, Auckland University of Technology Contestable Grants Fund and the Ministry of Health.

Assessment of bioelectrical impedance analysis for the prediction of total body water in cystic fibrosis

The aim of this study was to compare the measurement of total body water (TBW) by deuterium ((H2O)-H-2) dilution and bioelectrical impedance analysis (BIA) in patients with cystic fibrosis (CF) and healthy controls. Thirty-six clinically stable patients with CF (age 25.4 +/- 5.6 yrs) and 42 healthy controls (age 25.4 +/- 4.8) were recruited into this study. TBW was measured by (H2O)-H-2 dilution and predicted by BIA in patients and controls. The TBW predicted from BIA was significantly different from TBW as measured using (H2O)-H-2 in patients (P

Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme

The purpose of this investigation was to assess changes in total energy expenditure (TEE), body weight (BW) and body composition following a peripheral blood stem cell transplant and following participation in a 3-month duration, moderate-intensity, mixed-type exercise programme. The doubly labelled and singly labelled water methods were used to measure TEE and total body water (TBW). Body weight and TBW were then used to calculate percentage body fat (%BF), and fat and fat-free mass (FFM). TEE and body composition measures were assessed pretransplant (PI), immediately post-transplant (PII) and 3 months post-PII (PIII). Following PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). While there was no change in TEE between pre- and post-transplant, BW (P

Resting energy expenditure and body composition in children with myelomeningocele

Purpose : Myelomeningocele is a complex disease often complicated by obesity for reasons not well understood. The objectives of this study were to determine body composition and energy expenditure of children with MMC. Methods : Resting energy expenditure (REE), body composition and anthropometry were measured in 19 children with MMC (12 M, 7 F). Total energy expenditure (TEE) was estimated using a 3-day activity record. Energy intake (EI) was measured in seven children (5 M, 2 F) with MMC. Data were then compared with predicted values. Results : Mean REE ( n = 19) was 4680 ±1452 kJ/day (96.1 ±18.1% of predicted REE). The range was large (45.8-125.7% of predicted REE). TEE ( n = 7) was 4344 ±2376 kJ/day, hence only 73 34% of predicted TEE. EI ( n = 7) was 6560 ±1329 kJ/day, approximating a normal energy requirement. Overall, BCM was lower than expected values. Conclusions : REE in children with MMC is variable when compared to predicted values. TEE was found to be lower in children with MMC than predicted values and EI was similar to predicted values in this group of seven children. BCM is reduced in children with MMC when compared to expected values.

Measured and predicted total body water in children with myelomeningocele

Objective: Children with myelomeningocele (MMC) have an altered body composition and an atypical distribution of total body water (TBW). The aim of the present study was to determine the accuracy of current predictive equations, based on bioelectrical impedance analysis (BIA), in determining TBW when compared with measured TBW using deuterium dilution. Methods: Fourteen children with MMC were measured for whole body BIA and TBW (using deuterium dilution and the Plateau method). Total body water was predicted using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects. Results: The mean measured TBW was 15.46 +/- 8.28 L and the mean predictions for TBW using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects were 18.29 +/- 8.41 L, 17.72 +/- 11.42 L and 12.51 +/- 7.59 L, respectively. The best correlation was found using characteristic frequency. The limits of agreement between measured and predicted TBW values using Bland-Altman analysis were large. Conclusions: The present study suggests that the prediction of TBW in children with MMC can be made accurately using the equation of Cornish et al . based on BIA measurements of characteristic frequency.

Aging per se does not influence glucose homeostasis - In vivo and in vitro evidence

OBJECTIVE - To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity. RESEARCH DESIGN AND METHODS - Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women. RESULTS - Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women. CONCLUSIONS - 1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake.