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Biomedical subjects

D J Barker

Publications and source records attributed to D J Barker.

At least 19 recordsLinked to original sources
PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2003

Evaluating a spoken dialogue system for recording clinical observations during an endoscopic examination.

Paper, keyboard or mouse-driven systems may not be suitable for data capture because of the hands-busy constraint imposed by an endoscopic examination. A Spoken Dialogue System (SDS) has a number of advantages when compared to keyboard and mouse-driven input modalities, particularly with respect to hands free and eyes-free control of a system. However, any emerging technology will never deliver improved organizational effectiveness if it is not accepted and used. The Technology Acceptance Model (TAM) provides a framework that helps explain the determinants of computer acceptance. This study, through the application of TAM, demonstrates a high level of user acceptance with clinicians wanting to use spoken dialogue technology for recording clinical observations during an endoscopic examination. Clinicians would also prefer to use a SDS for recording endoscopy rather than use a paper-based or keyboard and mouse-driven system. Using a clinical narrative during an endoscopic examination was also perceived to be a natural way to record findings. Relationships between basic TAM variables were confirmed and relationships between quality of dialogue measures and TAM variables were established.

Adult↗
PubMed2002

The body as art.

For millennia people have altered the appearance of their bodies with cosmetics, jewellery, tattoos, piercings, and other surgical procedures. It would appear that they wish to conform to a perceived 'ideal body', although the actual appearance of such a body is subject to temporal, cultural and geographical change. In contemporary society the media are largely responsible for providing the yardsticks against which individual body shape is measured. Today the desired form is generally young, slim, tanned and blemish-free. Sadly, dissatisfaction with body image can be the source of great unhappiness and may even lead to suicide. Interested scholars have debated the meaning of beauty for centuries but it seems that every human society has its own standards. At the simplest it would appear that youth and symmetry are the most highly prized ingredients. There is no doubt that those who fit the conventional standards of attractiveness are treated better by society. Individuals have an inalienable right to their own body appearance, and to alter it as they see fit, however such modifications may not always be in their own best interests. Practitioners of cosmetic procedures must be alert to clients with histories of weight fluctuation, unrealistic body image, or low self-esteem. Psychological disorders may present with dysmorphophobic symptoms. Doctors providing cosmetic services need to be adept at diagnosing psychological illness.

Art↗
PubMed2001

Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.

Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

Adaptation, Physiological↗
PubMed2001

Size at birth and resilience to effects of poor living conditions in adult life: longitudinal study.

OBJECTIVE: To determine whether men who grew slowly in utero or during infancy are more vulnerable to the later effects of poor living conditions on coronary heart disease. DESIGN: Follow up study of men for whom there were data on body size at birth and growth and social class during childhood, educational level, and social class and income in adult life. SETTING: Helsinki, Finland. PARTICIPANTS: 3676 men who were born during 1934-44, attended child welfare clinics in Helsinki, were still resident in Finland in 1971, and for whom data from the 1980 census were available. MAIN OUTCOME MEASURES: Hospital admission for or death from coronary heart disease. RESULTS: Men who had low social class or low household income in adult life had increased rates of coronary heart disease. The hazard ratio among men with the lowest annual income (<8400 pound sterling) was 1.71 (95% confidence interval 1.18 to 2.48) compared with 1.00 in men with incomes above 15, 700 pound sterling. These effects were stronger in men who were thin at birth (ponderal index <26 kg/m(3)): hazard ratio 2.58 (1.45 to 4.60) for men with lowest annual income. Among the men who were thin at birth the effects of low social class were greater in those who had accelerated weight gain between ages 1 and 12 years. Low social class in childhood further increased risk of disease, partly because it was associated with poor growth during infancy. Low educational attainment was associated with increased risk, and low income had no effect once this was taken into account. CONCLUSION: Men who grow slowly in utero remain biologically different to other men. They are more vulnerable to the effects of low socioeconomic status and low income on coronary heart disease.

Aged↗
PubMed2001

High-meat, low-carbohydrate diet in pregnancy: relation to adult blood pressure in the offspring.

To examine the hypothesis that a high-animal protein, low-carbohydrate diet in pregnancy is associated with raised blood pressure in the adult offspring, we performed a follow-up study of 626 men and women in Motherwell, Scotland, whose mothers' food intake had been recorded during pregnancy. The mothers had taken part in a dietary intervention in which they were advised to eat 1 lb (0.45 kg) of red meat per day and to avoid carbohydrate-rich foods during pregnancy. The offspring were followed up at age 27 to 30 years, and their systolic and diastolic blood pressures were measured. Women who reported greater consumption of meat and fish in the second half of pregnancy had offspring with higher systolic blood pressure in adult life (regression coefficient, 0.19 mm Hg per portion per week; 95% confidence interval, 0.04 to 0.35; P=0.02). High maternal consumption of fish, but not meat, was associated with higher diastolic blood pressure in the offspring (regression coefficient, 1.00 mm Hg per portion per week; 95% confidence interval, 0.18 to 1.82; P=0.02). These associations were independent of maternal blood pressure, body size, and smoking habits during pregnancy. Although we cannot exclude confounding by maternal saturated fat or salt intake, the findings support those of a study in Aberdeen showing higher blood pressure in men and women whose mothers had eaten a high-animal protein, low-carbohydrate diet in late pregnancy. These associations may reflect the metabolic stress imposed on the mother by an unbalanced diet in which high intakes of essential amino acids are not accompanied by the nutrients required to utilize them.

Adult↗
PubMed2001

Tallness and overweight during childhood have opposing effects on breast cancer risk.

Using birth and school health records we studied how weight and height during childhood affect breast cancer risk among 3447 women born during 1924-33 at the University Hospital of Helsinki, Finland. Through linkages with the National Hospital Discharge Registry and the Cause of Death Registry we identified 177 women who during 1971-1995 had been admitted to hospital with breast cancer, of whom 49 had died from the disease. Of these, 135 (76%) were aged 50 years or more at the time of diagnosis, and therefore likely to have been post-menopausal. Hazard ratios for breast cancer rose with increasing weight and length at birth, though neither trend was statistically significant. At each age, from 7 to 15 years, the girls who later developed breast cancer were on average taller and had lower body mass than the other girls. Unadjusted hazard ratios rose across the range of height (P = 0.01 at age 7 years) and fell across the range of body mass index (P = 0.009 at age 7 years). In a simultaneous analysis the hazard ratio for breast cancer was 1.27 (95% CI 0.97-1.78, P = 0.08) for every kilogram increase in birth weight and 1.21 (95% CI 1.06-1.38, P = 0.004) for every kg/m(2) decrease in body mass index at 7. Our findings indicate that tallness in childhood is associated with increased risk of developing breast cancer. One possible explanation is persisting high plasma concentrations of insulin-like growth factors in tall women. In contrast, we found that being overweight in childhood reduces breast cancer risk. The increased adipose tissue-derived oestrogen levels in overweight children could induce early breast differentiation and eliminate some targets for malignant transformation.

Adolescent↗
PubMed2001

Early growth and coronary heart disease in later life: longitudinal study.

OBJECTIVE: To determine how growth during infancy and childhood modifies the increased risk of coronary heart disease associated with small body size at birth. DESIGN: Longitudinal study. SETTING: Helsinki, Finland. SUBJECTS: 4630 men who were born in the Helsinki University Hospital during 1934-44 and who attended child welfare clinics in the city. Each man had on average 18.0 (SD 9.5) measurements of height and weight between birth and age 12 years. MAIN OUTCOME MEASURES: Hospital admission or death from coronary heart disease. RESULTS: Low birth weight and low ponderal index (birth weight/length(3)) were associated with increased risk of coronary heart disease. Low height, weight, and body mass index (weight/height(2)) at age 1 year also increased the risk. Hazard ratios fell progressively from 1.83 (95% confidence interval 1.28 to 2.60) in men whose body mass index at age 1 year was below 16 kg/m(2) to 1.00 in those whose body mass index was >19 (P for trend=0.0004). After age 1 year, rapid gain in weight and body mass index increased the risk of coronary heart disease. This effect was confined, however, to men with a ponderal index <26 at birth. In these men the hazard ratio associated with a one unit increase in standard deviation score for body mass index between ages 1 and 12 years was 1.27 (1.10 to 1.47; P=0.001). CONCLUSION: Irrespective of size at birth, low weight gain during infancy is associated with increased risk of coronary heart disease. After age 1 year, rapid weight gain is associated with further increase in risk, but only among boys who were thin at birth. In these boys the adverse effects of rapid weight gain on later coronary heart disease are already apparent at age 3 years. Improvements in fetal, infant, and child growth could lead to substantial reductions in the incidence of coronary heart disease.

Aged↗
PubMed2001

Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood.

BACKGROUND: Nutritional factors in early life may contribute to the neurodevelopmental deficit in schizophrenia. This study explores the influence of maternal body size, size at birth, and childhood growth on future risk for schizophrenia. SUBJECTS AND METHODS: This population-based cohort study comprised births at Helsinki University Central Hospital in Helsinki, Finland, from 1924 to 1933. Prospective data from birth and school health records of 7086 individuals were collected and linked to the Finnish Hospital Discharge Register. RESULTS: Schizophrenia or schizoaffective disorder had been diagnosed in 114 individuals. A lower late-pregnancy maternal body mass index (BMI) increased the risk (odds ratio [OR], 1.09 per kilogram/meter(2); 95% confidence interval [CI], 1.02-1.17) for schizophrenia among the offspring. The risk of schizophrenia increased with low birth weight (OR, 1.48 per kilogram; 95% CI, 1.03-2.13), shortness at birth (OR, 1.12 per centimeter; 95% CI, 1.03-1.22), and low placental weight (OR, 1.22 per 100 g; 95% CI, 1.04-1.43). Schizophrenia cases were thinner than comparison subjects from 7 to 15 years of age. In a joint model comprising late-pregnancy maternal BMI, body size at birth, and childhood BMI, childhood BMI was an independent predictor of schizophrenia, whereas other factors exhibited attenuated effects. CONCLUSION: Indicators of intrauterine and childhood undernutrition are associated with an increased lifetime risk of schizophrenia.

Adolescent↗
PubMed2001

Maternal height, childhood growth and risk of hip fracture in later life: a longitudinal study.

Although measures to enhance bone mineralization during childhood and adolescence are widely incorporated into preventive programmes against osteoporotic fracture, there are no published data directly linking growth rates in childhood with the risk of later hip fracture. We addressed this issue in a unique Finnish cohort in whom birth and childhood growth data were linked to later hospital discharge records. This permitted follow-up of 3639 men and 3447 women who were born in Helsinki University Central Hospital between 1924 and 1933, who went to school in Helsinki and still lived in Finland in 1971. Body size at birth was recorded and an average of 10 measurements were obtained of height and weight throughout childhood. We identified 112 subjects (55 men and 57 women) who sustained a hip fracture during 165 404 person-years of follow-up. After adjustment for age and sex in a proportional hazards model, we identified two major determinants of hip fracture risk: tall maternal height (p < 0.001) and a low rate of childhood growth (height, p = 0.006; weight, p = 0.01). The hazard ratio for hip fracture was 2.1 (95% CI 1.2-3.5) among men and women born to mothers taller than 1.61 m, when compared with those whose mothers were shorter than 1.54 m. The ratio was 1.9 (95% CI 1.1-3.2) among those whose rate of childhood height gain was below the lowest quartile for the cohort, compared with those whose growth rate was above the highest quartile. The effects of maternal height and childhood growth rate were statistically independent of each other, and remained after adjusting for socioeconomic status. The patterns of childhood growth that predicted future hip fracture differed between boys and girls. In boys, there was a constant deficit in height and weight between ages 7 and 15 years among those later sustaining fractures; in girls, there was a progressively increasing deficit in weight but a delayed height gain among those later sustaining fractures. This epidemiologic study provides the first direct evidence that a low rate of childhood growth is a risk factor for later hip fracture. Whether reduced growth rate is a consequence of childhood lifestyle, genetic background or intrauterine hormonal programming, the data support measures to optimize childhood growth as part of preventive strategies against osteoporotic fracture in future generations.

Adolescent↗
PubMed2001

A new model for the origins of chronic disease.

Living things are often plastic during their early development and are moulded by the environment. Many human fetuses have to adapt to a limited supply of nutrients, and in doing so they permanently change their physiology and metabolism. These programmed changes may be the origins of a number of diseases in later life, including coronary heart disease, stroke, diabetes and hypertension.

Causality↗
PubMed2001

Associations between childhood living circumstances and schizophrenia: a population-based cohort study.

OBJECTIVE: It has been suggested that household crowding may constitute an environmental risk factor for schizophrenia. The present population-based cohort study explores the associations of childhood family size and living conditions to schizophrenia. METHOD: The cohort comprised people born at Helsinki University Central Hospital from 1924 to 1933, who went to school in the city and were still living in Finland in 1971. Prospectively gathered data from birth and school health records of these 7086 individuals were collected and linked to the Finnish Hospital Discharge Register. RESULTS: Ninety-eight cases of schizophrenia were identified in the cohort. Number of siblings at school start was significantly associated with schizophrenia when adjusted for sex and age of mother. Number of siblings was negatively correlated with body mass index at age 7. Childhood household crowding, defined as number of people per room, and total number of rooms in household were not significantly associated with schizophrenia. CONCLUSION: Our study indicates that the total number siblings in household during childhood is of greater importance than childhood number of inhabitants per room. Subjects who originated from families with many children had been leaner, which may imply that childhood nutritional factors partly is the mediating factor between number of siblings and schizophrenia. Other possible underlying mechanisms of the associations found include infectious and psychological factors.

Adolescent↗
PubMed2001

Adult survival after prenatal exposure to the Dutch famine 1944--45.

Early life events may affect adult survival. We studied the effect of prenatal exposure to the Dutch famine 1944--45 on survival among 2254 people born in Amsterdam. Mortality up to age 50 was highest among those born before the famine (15.2%) and among those exposed to famine in late gestation (14.6%). It was lower among those exposed in mid- (11.2%) or early gestation (11.5%), and was lowest among those conceived after the famine (7.2%). These differences were caused by effects on mortality in the first year after birth and were mainly related to nutrition and infections. There was no effect of exposure to famine on mortality after the age of 18. The hazard ratio was 1.4 [0.8, 2.3] for those born before the famine, 1.1 [0.5, 2.3] for those exposed in late gestation, 0.8 [0.3, 1.8] for those exposed in mid-gestation and 1.1 [0.5, 2.5] in those exposed in early gestation compared with those conceived after the famine. We could not demonstrate effects of prenatal exposure to famine on cause-specific mortality after the age of 18. Because prenatal exposure to famine is linked to cardiovascular risk factors and disease, increased cardiovascular mortality in the future may be expected.

Adult↗
PubMed2001

Fetal programming and adult health.

Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may result from adaptations invoked when the materno-placental nutrient supply fails to match the fetal nutrient demand. Although the influences that impair fetal development and programme adult cardiovascular disease remain to be defined, there are strong pointers to the importance of maternal body composition and dietary balance during pregnancy.

Adult↗
PubMed2001

The thrifty phenotype hypothesis.

The thrifty phenotype hypothesis proposes that the epidemiological associations between poor fetal and infant growth and the subsequent development of type 2 diabetes and the metabolic syndrome result from the effects of poor nutrition in early life, which produces permanent changes in glucose-insulin metabolism. These changes include reduced capacity for insulin secretion and insulin resistance which, combined with effects of obesity, ageing and physical inactivity, are the most important factors in determining type 2 diabetes. Since the hypothesis was proposed, many studies world-wide have confirmed the initial epidemiological evidence, although the strength of the relationships has varied from one study to another. The relationship with insulin resistance is clear at all ages studied. Less clear is the relationship with insulin secretion. The relative contribution of genes and environment to these relationships remains a matter of debate. The contributions of maternal hyperglycaemia and the trajectory of postnatal growth need to be clarified.

Birth Weight↗
PubMed2001

The malnourished baby and infant.

The growth of a baby is constrained by the nutrients and oxygen it receives from the mother. A mother's ability to nourish her baby is established during her own fetal life and by her nutritional experiences in childhood and adolescence, which determine her body size, composition and metabolism. Mother's diet in pregnancy has little effect on the baby's size at birth, but nevertheless programmes the baby. The fetus adapts to undernutrition by changing its metabolism, altering its production of hormones and the sensitivity of tissues to them, redistributing its blood flow, and slowing its growth rate. In some circumstances, the placenta may enlarge. Adaptations to undernutrition that occur during development permanently alter the structure and function of the body.

Adaptation, Physiological↗