Bone growth and exercise studies: The complications of maturation.
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Publications and source records attributed to D A Bailey.
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The expression of 1008 open reading frames (ORFs) from the yeast Saccharomyces cerevisiae has been examined under eight different physiological conditions, using classical northern analysis. These northern data have been compared with publicly available data from a microarray analysis of the diauxic transition in S.cerevisiae. The results demonstrate the importance of comparing biologically equivalent situations and of the standardization of data normalization procedures. We have also used our northern data to identify co-regulated gene clusters and define the putative target sites of transcriptional activators responsible for their control. Clusters containing genes of known function identify target sites of known activators. In contrast, clusters comprised solely of genes of unknown function usually define novel putative target sites. Finally, we have examined possible global controls on gene expression. It was discovered that ORFs that are highly expressed following a nutritional upshift tend to employ favoured codons, whereas those overexpressed in starvation conditions do not. These results are interpreted in terms of a model in which competition between mRNA molecules for translational capacity selects for codons translated by abundant tRNAs.
A mini-Tn5 transposon was modified to introduce a promoterless luxCDABE cassette from Vibrio fischeri into environmentally relevant bacterial strains in order to develop bioluminescence-based biosensors for toxicity testing. The mini-Tn5 luxCDABE transposon was chromosomally integrated downstream from an active promoter into two Pseudomonas strains (Pseudomonas fluorescens 8866 and Pseudomonas putida F1). Characterisation of the bioluminescent transconjugants demonstrated that the transposon integration was stable and had no effect on growth rate. Both P. fluorescens 8866 Tn5 luxCDABE and P. putida F1 Tn5 luxCDABE were used to assess the toxicity of standard solutions (Cu, Zn and 3,5-DCP) as well as Cu- and 3,5-DCP-spiked groundwater samples. They were successfully used for bioluminescence-based bioassays and the potential value of using different bacterial biosensors for ecotoxicity testing was shown.
OBJECTIVE: We examined the relationship between self-reported calcium (Ca) intake and bone mineral content (BMC) in children and adolescents. We hypothesized that an expression of Ca adjusted for energy intake (EI), i.e., Ca density, would be a better predictor of BMC than unadjusted Ca because of underreporting of EI. METHODS: Data were obtained on dietary intakes (repeated 24-hour recalls) and BMC (by DEXA) in a cross-section of 227 children aged 8 to 17 years. Bivariate and multivariate analyses were used to examine the relationship between Ca. Ca density, and the dependent variables total body BMC and lumbar spine BMC. Covariates included were height, weight, bone area. maturity age, activity score and EI. RESULTS: Reported EI compared to estimated basal metabolic rate suggested underreporting of EI. Total body and lumbar spine BMC were significantly associated with EI, but not Ca or Ca density, in bivariate analyses. After controlling for size and maturity, multiple linear regression analysis revealed unadjusted Ca to be a predictor of BMC in males in the total body (p = 0.08) and lumbar spine (p = 0.01)). Unadjusted Ca was not a predictor of BMC at either site in females. Ca density was not a better predictor of BMC at either site in males or females. CONCLUSIONS: The relationship observed in male adolescents in this study between Ca intake and BMC is similar to that seen in clinical trials. Ca density did not enable us to see a relationship between Ca intake and BMC in females, which may reflect systematic reporting errors or that diet is not a limiting factor in this group of healthy adolescents.
Bone-mineral content (BMC; g) and density (BMD; g/cm2) were measured by dual energy X-ray absorptiometry in the proximal femur, femoral neck, and total body of nutritionally adequate children (n=17; 11 girls, six boys; aged 7.6 to 13.8 years) with spastic cerebral palsy (CP). Bone-mineral-free lean tissue (BMFL; g) and fat mass (FM; g) were obtained from total body scans. Chronological and developmental age-based z scores for the children with CP were derived from a pediatric database (n=894). Children with CP had BMC z scores from -1.8 (total body) to -3.2 (femoral neck) SDs below the normative sample. Non-independent ambulators had lower z scores for total body BMD, femoral neck BMD, and BMC than independent ambulators. The BMFL z score of individuals with CP was 2 SDs below that of the reference group and higher in the independent ambulators than in the non-independent ambulators, whereas FM deviated little. These findings suggest that non-nutritional factors, such as ambulation, account for the low BMC, BMD, and BMFL tissue observed in this population.
The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BMC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.
Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN). In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001). Changes in FN area and BMC over 8 months were significantly greater (2.3%, p < 0.05) using a narrower FN rather than the default ROI. Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001). For aBMD there were no significant differences in group means between analysis methods at either the PF or FN. Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.
After an 8-month physical activity intervention in children with cerebral palsy, increases in femoral neck bone mineral content (BMC) (9.6%), volumetric bone mineral density (v BMD) (5.6%), and total proximal femur BMC (11.5%) were observed in the intervention group (n = 9) compared with control subjects (n = 9; femoral neck BMC, -5. 8%; v BMD, -6.3%; total proximal femur BMC, 3.5%).
To investigate the influence of physical activity on bone mineral accrual during the adolescent years, we analyzed 6 years of data from 53 girls and 60 boys. Physical activity, dietary intakes, and anthropometry were measured every 6 months and dual-energy X-ray absorptiometry scans of the total body (TB), lumbar spine (LS), and proximal femur (Hologic 2000, array mode) were collected annually. Distance and velocity curves for height and bone mineral content (BMC) were fitted for each child at several skeletal sites using a cubic spline procedure, from which ages at peak height velocity (PHV) and peak BMC velocity (PBMCV) were identified. A mean age- and gender-specific standardized activity (Z) score was calculated for each subject based on multiple yearly activity assessments collected up until age of PHV. This score was used to identify active (top quartile), average (middle 2 quartiles), or inactive (bottom quartile) groups. Two-way analysis of covariance, with height and weight at PHV controlled for, demonstrated significant physical activity and gender main effects (but no interaction) for PBMCV, for BMC accrued for 2 years around peak velocity, and for BMC at 1 year post-PBMCV for the TB and femoral neck and for physical activity but not gender at the LS (all p < 0.05). Controlling for maturational and size differences between groups, we noted a 9% and 17% greater TB BMC for active boys and girls, respectively, over their inactive peers 1 year after the age of PBMCV. We also estimated that, on average, 26% of adult TB bone mineral was accrued during the 2 years around PBMCV.
BACKGROUND AND OBJECTIVES: The greatest increase in bone mineral content occurs during adolescence. The amount of bone accrued may significantly affect bone mineral status in later life. We carried out a longitudinal investigation of the magnitude and timing of peak bone mineral content velocity (PBMCV) in relation to peak height velocity (PHV) and the age at menarche in a group of adolescent girls over a 6-year period. METHODS: The 53 girls in this study are a subset of the 115 girls (initially 8 to 16 years) in a 6-year longitudinal study of bone mineral accretion. The ages at PBMCV and PHV were determined by using a cubic spline curve fitting procedure. Determinations were based on height (n = 12) and bone (n = 6) measurements over 6 years. RESULTS: The timing of PBMCV and menarche were coincident, preceded approximately 1 year earlier by PHV. Correlation showed a negative relationship between age at menarche and both peak bone mineral accrual (r = -0.42, P < .002) and PHV (r = -0.45, P < .001). CONCLUSIONS: This longitudinal study demonstrated the close association between age at PBMCV and age at menarche and confirmed the relationship between greater PBMCV and PHV in earlier, as compared with later, maturing girls.
To investigate bone mineral accretion in growing children, the Saskatchewan Pediatric Bone Mineral Accrual Study was initiated in 1991. The study involves the collection of dietary and physical activity information along with anthropometric growth and maturity measurements every 6 months and dual-energy X-ray absorptiometer (DXA) bone scans of the whole body, AP lumbar spine and proximal femur taken annually. The study has now finished its 6th year and 68 males and 72 females from an original sample of 228 elementary schoolchildren are still involved. To investigate how bone mineral at clinically important sites proceeds in relation to maturation we developed distance and velocity growth curves for height and bone mineral content (BMC) for the AP lumbar spine, the femoral neck and the whole body. In both boys and girls, over 35% of total body and AP spine bone mineral and over 27% of the bone mineral at the femoral neck was laid down during the 4-year adolescent period surrounding peak linear growth velocity. The clinical significance of these values can be appreciated by consideration of the fact that as much bone mineral will be laid down during these 4 adolescent growing years as most people will lose during all of adult life.
We measured bone mineral content (BMC) and estimated calcium accretion in children to provide insight into dietary calcium requirements during growth. Anthropometric measurements were done semiannually and whole-body BMC was measured annually by dual-energy X-ray absorptiometry for 4 y in 228 children (471 scans in 113 boys and 507 scans in 115 girls). Mean values for BMC, skeletal area, and height were calculated for 1-y age groups from 9.5 to 19.5 y of age. Cross-sectional analysis of the pooled data gave peak height velocity and peak BMC velocity (PBMCV) and the ages at which these occurred (13.3 y in boys and 11.4 y in girls). PBMCV did not peak until 1.2 y after peak height velocity in boys and 1.6 y after peak height velocity in girls. Within 3 y on either side of PBMCV, boys had consistently higher BMC and BMC velocity compared with girls and the discrepancy increased steadily through puberty. Three years before PBMCV, BMC values in girls were 69% of those in boys; 3 y after peak height velocity this proportion fell to 51%. PBMCV was 320 g/y in boys and 240 g/y in girls. Under the assumption that bone mineral is 32.2% calcium, these values corresponded to a daily calcium retention of 282 mg in boys and 212 mg in girls. Individual values could be much greater. In one boy in a group of six subjects for whom there were enough data for individual analysis through puberty, PBMCV was 555 g Ca/y or 490 mg Ca/d. Such high skeletal demands for calcium require large dietary calcium intakes and such requirements may not be met immediately in some children.
As competition for patient volume escalates among hospital providers, administrators must identify ways to attract new patients and maintain or increase patient volume. Family care givers are known to greatly influence individuals' choices in these matters of selection of healthcare services and providers. The results of a successful nurse-initiated daily phone calls program, designed to improve family care giver satisfaction by enhancing the provision of patient-specific information, are presented. The components of the program, associated costs, and implications on delivery of care are discussed.
This article reports three studies that investigated psychometric properties of the Physical Activity Questionnaire for Older Children (PAQ-C). The PAQ-C is a guided self-administered 7-day recall measure designed to assess general physical activity levels during the school year for children in grades four and higher. Study one, with 215 students ranging in age from 9 to 15 yr, found the PAQ-C had acceptable item and test score characteristics such as item distribution, corrected item-total correlations, and internal consistency. Study two, involving 84 students ranging from 9 to 14 yr, indicated acceptable levels of test-retest reliability for both males (r = 0.75) and females (r = 0.82) after 1 wk. The third study used Generalizability theory to investigate the reliability for using the average of either two or three PAQ-C scores collected during fall, winter, and spring seasons. Based on the responses of 200 students ranging from 8 to 16 yr, generalizability coefficients exceeded 0.80 for either the average of two or three responses for both younger (<13 yr) and older subjects. In all three studies, the PAQ-C demonstrated acceptable internal consistency and males were significantly more active than females. These results provide preliminary support for the PAQ-C as a cost efficient method of assessing general levels of children's physical activity during the school year.
Maximization of bone accrual during the growing years is thought to be an important factor in minimizing fracture risk in old age. Mechanical loading through physical activity has been recommended as a modality for the conservation of bone mineral in adults; however, few studies have evaluated the impact of different loading regimes in growing children. The purpose of this study was to compare bone mineral density (BMD) in weight-bearing and non-weight-bearing limbs in 17 children with unilateral Legg Calvé Perthes Disease (LCPD). Children with this condition have an altered weight-bearing pattern whereby there is increased mechanical loading on the noninvolved normal hip and reduced loading on the involved painful hip. Thus, these children provide a unique opportunity to study the impact of differential mechanical loading on BMD during the growing years while controlling for genetic disposition. BMD at four regions of the proximal femur (trochanter, intertrochanter, femoral neck, total of the regions) was measured using dual energy x-ray absorptiometry (DXA), and the values were compared between the involved and noninvolved sides of the children with LCPD. The BMD of the both sides also were compared with normative values based on both chronological and skeletal age data. A significantly higher BMD was found on the noninvolved side over the involved side for all regions (P < 0.01 and percentage differences of 12-15%) except at the femoral neck (percentage difference of 3.9%). The BMD (at all regions) of the noninvolved side also was significantly greater (P < 0.01) than either the chronological or skeletal age based norms for all sites except the trochanter. The results support the concept that mechanical loading of the skeleton during the growing years is an important factor in BMD accrual.
Normative bone mineral density (BMD) and bone mineral content (BMC) values for the total body (TB), proximal femur (PF), and antero-posterior lumbar spine (LS) were obtained from a large cross-sectional sample of children and adolescents who were 8-17 years of age. There were 977 scans for the TB, 892 for the PF, and 666 for the LS; bone mineral values were obtained using a HOLOGIC QDR 2000 in array mode. Data are presented for the subregions of the PF (femoral neck, trochanter, intertrochanter, and the total region) and for the LS (L1-L4 and L3). Female and male values for the FN, LS (L1-L4), and the TB were compared across age groups using a two-way ANOVA. In addition, we compared the 17-year-old female values to a separate sample of young adult women (age 21). At all these sites, BMC and BMD increased significantly with age. There was no gender difference in TB BMC until age 14 or in TB BMD until age 16, when male values were significantly greater. Females had significantly greater LS BMC at ages 12 and 13, but by age 17 the male values were significantly greater. Females had significantly greater LS BMD across all age groups, however. Males had significantly greater FN BMC and BMD across all age groups. There were no significant differences in BMC or BMD at any sites between the 17- and 21-year-old women.
A hyphally regulated gene (HYR1) from the dimorphic human pathogenic fungus Candida albicans was isolated and characterized. Northern (RNA) analyses showed that the HYR1 mRNA was induced specifically in response to hyphal development when morphogenesis was stimulated by serum addition and temperature elevation, increases in both culture pH and temperature, or N-acetylglucosamine addition. The HYR1 gene sequence revealed a 937-codon open reading frame capable of encoding a protein with an N-terminal signal sequence, a C-terminal glycosylphosphatidylinositol-anchoring domain, 17 potential N glycosylation sites, and a large domain rich in serine and threonine (51% of 230 residues). These features are observed in many yeast cell wall proteins, but no homologs are present in the databases. In addition, Hyr1p contained a second domain rich in glycine, serine, and asparagine (79% of 239 residues). The HYR1 locus in C. albicans CAI4 was disrupted by "Ura-blasting," but the resulting homozygous delta hyr1/delta hyr1 null mutant displayed no obvious morphological phenotype. The growth rates for yeast cells and hyphae and the kinetics of germ tube formation in the null mutant were unaffected. Aberrant expression of HYR1 in yeast cells, when an ADH1-HYR1 fusion was used, did not stimulate hyphal formation in C. albicans or pseudohyphal growth in Saccharomyces cerevisiae. HYR1 appears to encode a nonessential component of the hyphal cell wall.
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