Bone mineral measurements.
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Biomedical subjects
Publications and source records attributed to T J Cole.
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We have characterized the gene for the mouse glucocorticoid receptor. The gene spans approximately 110 kilobases, and glucocorticoid receptor transcripts are assembled from nine exons. Expression of the gene is controlled by at least three promoters, resulting in glucocorticoid receptor transcripts with different 5' nontranslated exons. One promoter is cell-specific, found to be active only in T lymphocytes. The other two promoters are active to various degrees in all cell lines and tissues so far analyzed and are located in a CpG island. The promoter activities are accompanied by DNase I hypersensitivity sites in chromatin. In contrast to a conservation of exon-intron structure, differences in promoter organization suggest a divergence between the evolution of regulatory and coding regions among members of the steroid receptor super-family.
There is considerable controversy over whether nutrition in early life has a long-term influence on neurodevelopment. We have shown previously that, in preterm infants, mother's choice to provide breast milk was associated with higher developmental scores at 18 months. We now report data on intelligence quotient (IQ) in the same children seen at 7 1/2-8 years. IQ was assessed in 300 children with an abbreviated version of the Weschler Intelligence Scale for Children (revised Anglicised). Children who had consumed mother's milk in the early weeks of life had a significantly higher IQ at 7 1/2-8 years than did those who received no maternal milk. An 8.3 point advantage (over half a standard deviation) in IQ remained even after adjustment for differences between groups in mother's education and social class (p less than 0.0001). This advantage was associated with being fed mother's milk by tube rather than with the process of breastfeeding. There was a dose-response relation between the proportion of mother's milk in the diet and subsequent IQ. Children whose mothers chose to provide milk but failed to do so had the same IQ as those whose mothers elected not to provide breast milk. Although these results could be explained by differences between groups in parenting skills or genetic potential (even after adjustment for social and educational factors), our data point to a beneficial effect of human milk on neurodevelopment.
We have characterized cDNA clones representing mouse CREB (cyclic AMP responsive element binding protein) mRNA isoforms. These include CREB delta and CREB alpha, of which the rat and human homologues have been previously identified. Both encode proteins with CRE-binding activity and identical transactivation potential. The additional CREB mRNA isoforms potentially encode CREB related proteins. From the structural organization of the mouse CREB gene we conclude that the multiple transcripts are generated by alternative splicing. Furthermore we show that specific CREB mRNA isoforms are expressed at a high level in the adult testis. Expression of these isoforms is induced after commencement of spermatogenesis. In situ hybridization suggests that this expression occurs predominantly in the primary spermatocytes. Comparison of the CREB gene with the recently isolated CREM (cAMP responsive element modulator) cDNAs illustrates that the two genes have arisen by gene duplication and have diverged to encode transcriptional activators and repressors of the cAMP signal transduction pathway.
Refence centile curves show the distribution of a measurement as it changes according to some covariate, often age. The LMS method summarizes the changing distribution by three curves representing the median, coefficient of variation and skewness, the latter expressed as a Box-Cox power. Using penalized likelihood the three curves can be fitted as cubic splines by non-linear regression, and the extent of smoothing required can be expressed in terms of smoothing parameters or equivalent degrees of freedom. The method is illustrated with data on triceps skinfold in Gambian girls and women, and body weight in U.S.A. girls.
T-kininogen plays an important role in the acute phase response to trauma in the rat as a possible source of kinins and as a cysteine proteinase inhibitor. Two T-kininogens are expressed by rat liver from two separate genes. T-kininogen expression in liver during the acute phase response is regulated at the level of transcription. The similarity in T- and K-kininogen gene structure suggests divergent evolution from a common gene ancestor.
One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 micrograms/l to a median of 12 micrograms/l, by the 2nd-3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 micrograms/l and a maximum of 1000 micrograms/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05-0.2 mg folate may be preferable for well preterm infants.
In this paper we report the isolation and characterization of the mouse CREB gene. It is composed of 11 exons and 10 introns and spans a region of 70 kb. BR-A and BR-B, the two alpha-helical regions of the proposed basic DNA binding domain of CREB, are encoded separately on exons 10 and 11. The mouse CREB gene is expressed from a promoter that is situated in a CpG island. The promoter contains no TATA or CCAAT box homologies but has a number of putative binding sites for the acidic transcriptional activator Sp1 and a 9/11 match with the initiator region. Transcriptional start site mapping identified five major start sites spread over at least 41 nucleotides. Northern blot analysis indicated that expression of the CREB gene is almost ubiquitous with expression at differing levels of multiple transcripts. Testis expressed a predominant RNA species of approximately 1.6 kb. The CREB gene was found to be single copy in the mouse and well conserved through evolution. Finally Creb-1, the CREB locus, was mapped to the proximal region of mouse chromosome 1.
It is frequently claimed that weight cycling, or "yo-yo" dieting, causes an inappropriate and permanent loss of lean body mass (LBM). Data are presented from a rural African population that undergoes profound weight cycling caused by an annual hungry season. No detrimental effect on LBM was observed. Data are also presented from an 18-wk prospective study of moderately obese British women who underwent three cycles of VLCD-induced weight loss and subsequent relapse. The proportion of weight lost as LBM was no greater than predicted. A review of the published results from experimental weight cycling in small animals also shows a high level of consensus that cycling does not significantly alter body composition. We conclude that, although weight cycling may affect growth of young animals, metabolic efficiency, and health, these effects are not mediated through permanent alterations in body composition.
Rectal and axillary temperatures were measured during the daytime in 281 infants seen randomly at home and 656 at hospital under 6 months old, using mercury-in-glass thermometers. The normal temperature range derived from the babies at home was 36.7-37.9 degrees C for rectal temperature and 35.6-37.2 degrees C for axillary temperature. Rectal temperature was higher than axillary in 98% of the measurements. The mean (SD) difference between rectal and axillary temperatures was 0.7 (0.5) degrees C, with a range of 3 degrees C. When used in hospital to detect high temperature, axillary temperature had a sensitivity of 73% compared with rectal temperature. This is too insensitive for accurate detection of an infant's high temperature. Rectal temperature measurement is safer than previously suggested: perforation has occurred in less than one in two million measurements. If an infant's temperature needs to be taken, rectal temperature should be used.
It is well known that deprivation affects bone growth. The study was set up to investigate what aspects of deprivation are of greatest importance. Bone ages of 1593 child trauma patients aged 0-19 years from Middlesbrough General Hospital, Cleveland, were related to local authority ward indices of socioeconomic status (51 wards). After adjustment for chronological age and sex, the mean bone ages in each ward were highly significantly negatively associated with five ward indices of deprivation: the rate of single parent families, low care ownership, unemployment, rented housing, and overcrowding. There was a mean four month deficit in bone age among children living in wards with the highest single parent family rates. The inverse association between deprivation and bone age is unlikely to be causal throughout childhood, as older and younger children were affected to the same extent. However the bone age deficit could be caused by deprivation retarding skeletal maturation during a critical period in early life.
In a randomised double blind trial, the effect on growth and clinical status of a nutrient enriched 'post-discharge' milk formula versus a standard term formula, was compared in 32 exclusively bottle fed preterm infants. The formulas were used as the sole milk intake up to a postnatal age of 9 months. Significant increases in linear growth and weight gain were observed in the infants who received the enriched diet. There were no differences in vomiting, posseting, or bowel habit between the groups. Formula volumes ingested were similar between diet groups, indicating that the difference in formula composition did not affect the infants' regulation of intake. These preliminary data suggest that there is a role for specially designed formulas for preterm infants after discharge from hospital.
Two-point or multipoint, that is the question. Equations are developed to compare the precision and accuracy of energy expenditure, as estimated from doubly labeled water data, when analyzed by the multipoint and two-point methods. The equations convert the enrichments of deuterium and oxygen-18 into their ratio and product, quantities that are less covariant than the two isotopes themselves are. This is important not only for estimating the precision but also as a graphical aid, since the ratios of the enrichments model carbon dioxide production, whereas the enrichment products largely model water turnover. Using data on 12 human subjects from the United Kingdom and The Gambia as examples, the combined precision and accuracy of the multipoint method (CV 3.6%) was found to be appreciably better than the two-point method (CV 5.4%). The bias in the multipoint estimate of body pool size would need to be three times as large as was observed before it canceled out the better precision.
We have investigated whether the Lunar DPX (software 3.4) and Hologic QDR-1000 dual-energy X-ray absorptiometers have comparable normal reference databases for the spine and femur of white UK and USA subjects. After conversion for systematic differences in absolute bone density values between the two systems, the reference databases were very similar for the spine in young subjects, but there were clear differences in the femur databases of young females and males of all ages. These differences were confirmed by comparing the percent age-matched and young values determined by the two systems for subjects scanned on both systems. Thus the diagnosis and management of a patient could differ, depending on the system used for the bone density measurements.
The bone mineral content (BMC) of the mid-shaft radius was measured in 446 rural Gambian and 349 British women aged 18-80+ years using single-photon absorptiometry. The two groups of women differed substantially in habitual calcium intake, calcium requirements for reproduction, physical activity and incidence of minimal-trauma fractures. The relationships of BMC with bone width (BW) and with body weight and height were explored using stepwise multiple regression analysis. The pattern of BMC with age was similar in The Gambia and Britain; BMC increased slightly to a peak at the end of the fourth decade followed by a decrease of about 30% between 40 and 70+ years. Gambian women had significantly lower BMC than British women of the same age (-5.6%, P less than 0.001) but after adjusting for weight, height and BW, the BMC of Gambian women was shown to be slightly higher than that of British women (+2.1%, P less than 0.05).
The relationships between bone width and mineral content and age, sex, height and weight were studied in 420 children aged 4-10 years living in Cambridge using single photon absorptiometry. The relationship of bone width with bone mineral content was significantly different between the sexes after adjusting for differences in body size. In addition, bone width in boys was found to be greater for a given height and weight; changes in weight had a greater effect on bone width in boys than in girls. Prediction equations for bone width and mineral content based on height and weight are given, which should enhance the application of single photon absorptiometry in clinical practice.
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The objective of the study was to relate blood pressure levels in children to their mother's weight in pregnancy. The blood pressures of 675 children aged from one to nine years in three villages in rural Gambia were measured. They were matched to antenatal clinic data which had been collected from all pregnant women in the three villages since 1980. Among children under eight years of age those born in the dry season had the highest blood pressures and were heavier. Their blood pressures were positively related to body weight and to mothers' weight at six months of pregnancy. These relationships were independent of mothers' age and parity, birthweight, gestational age, and placental weight. Among older children, aged eight and nine years, those born in the rainy season had the highest blood pressures. Their blood pressures were not related to their mothers' weight at six months of pregnancy. Rather they were inversely related to mothers' weight gain in the last trimester. An interpretation of these findings is that among young children differences in blood pressure are largely determined by rates of maturation. However, the long-term effects of adverse intra-uterine influences which elevate blood pressure become apparent in older children.