PubMed Health⌕ Search

Biomedical subjects

D A Leon

Publications and source records attributed to D A Leon.

At least 19 recordsLinked to original sources
PubMed2006

The associations of birthweight, gestational age and childhood BMI with type 2 diabetes: findings from the Aberdeen Children of the 1950s cohort.

AIMS/HYPOTHESIS: The aim of this study was to examine the associations of birthweight, gestational age and childhood BMI (assessed at a mean age of 5 years) with a self-report of a doctor diagnosis of diabetes in middle age. METHODS: We studied a birth cohort of 5,793 individuals who were born between 1950 and 1956 in Aberdeen, Scotland, and who responded to a questionnaire administered in 2000. RESULTS: Birthweight and gestational age were inversely associated with diabetes. These associations remained with additional adjustment for indicators of childhood and adult socioeconomic position, maternal complications of pregnancy, adult smoking, adult BMI and simultaneous adjustment for each other: the adjusted odds ratio per unit increase in birthweight z score was 0.73 (95% CI 0.60-0.88), the odds ratio per week increase in gestational age was 0.91 (95% CI 0.82-1.00) and odds ratio for preterm birth was 2.04 (94% CI 1.18-3.53). The positive association of childhood BMI with diabetes was attenuated on adjustment for adult BMI. CONCLUSIONS/INTERPRETATION: In this population, who were born in the 1950s, poor intrauterine growth and preterm birth are associated with an increased risk of diabetes.

Birth Weight↗
PubMed2006

Childhood intelligence, educational attainment and adult body mass index: findings from a prospective cohort and within sibling-pairs analysis.

BACKGROUND: The mechanisms underlying the observed association of childhood intelligence with body mass index (BMI) are unclear and few studies of this association have been prospective in design. METHODS: Prospective study in a birth cohort of 5467 individuals who were born in Aberdeen, Scotland between 1950 and 1956 and who responded to a follow-up survey in 2001. Comparison of associations within sibling pairs of the same family to associations between different families in 643 sibling pairs (1286 individuals) who are participants in the main cohort. RESULTS: Childhood intelligence (age 7 years) and educational attainment were both inversely associated with adult BMI (mean age 48 years): the sex- and age-adjusted mean change in adult BMI per s.d. of intelligence was -0.35 kg/m(2) (95% CI: -0.49, -0.21 kg/m(2)) and per unit increase in educational category (seven categories) was -0.28 kg/m(2) (95% CI: -0.34, -0.22). On adjustment for education the association between childhood intelligence and adult BMI attenuated to the null (-0.03 kg/m(2) (-0.19, 0.13 kg/m(2))); other potential confounding or mediating factors had little or only modest effects on this association. The association between education and adult BMI was not affected by adjustment for childhood intelligence or other potential covariates. The within sibling-pair effect of education on adult BMI (-0.06 kg/m(2) (95% CI: -0.26, 0.14)) was weaker than the effect between different families (-0.37 kg/m(2) (95%CI: -0.58, -0.17)), P-value for difference of within sibling and between family effect=0.03. CONCLUSIONS: The association of childhood intelligence with adult BMI is attenuated to the null on adjustment for educational attainment, whereas the association of educational attainment with adult BMI appears to be independent of childhood intelligence and other measured covariates. However, our family analyses suggest that fixed family and neighbourhood factors, which are closely matched in siblings of a similar age, explain much of the association between greater educational attainment and lower adult BMI.

Body Mass Index↗
PubMed2005

Birth weight, hypertension and "white coat" hypertension: size at birth in relation to office and 24-h ambulatory blood pressure.

We investigated the association of size at birth with hypertensive status defined by office blood pressure (BP) and 24-h ambulatory BP monitoring in a historical cohort study of 736 men born 1920-1924 and examined at age 70 years. Office BP was measured after 10-min supine rest with a sphygmomanometer, ambulatory BP was recorded with Accutracker 2, and anthropometric and other measurements were taken at a clinic. Birth weight and gestational age were abstracted from the men's birth records. A total of 24% of the men were treated for hypertension at the time of the study. Among not treated subjects, there was a weak positive association of birth weight with daytime and 24-h diastolic ambulatory BP. In subjects treated for hypertension, both office and ambulatory BP were inversely related to birth weight, although these associations were not statistically significant. Birth weight did not show significant association with sustained hypertension (elevated office and daytime ambulatory BPs) but showed a strong and statistically significant inverse association with "white coat" hypertension (elevated office BP and normal daytime ambulatory BP) when adjusted for concurrent body mass index (odds ratios 1.91, 1.59, 1 and 1.21 from lowest to highest quartile of birth weight, P-value for trend 0.035). We conclude that BP measured by 24-h-ambulatory monitoring is not related to birth weight in a pattern previously reported for office BP and that factors related to growth in utero are particularly related to higher risk of "white coat" hypertension.

Aged↗
PubMed2003

Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort.

OBJECTIVE: To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. DESIGN: Cohort identified from detailed birth records, with 97% follow up. SETTING: Uppsala Academic Hospital, Sweden. PARTICIPANTS: 5358 singleton females born during 1915-29, alive and traced to the 1960 census. MAIN OUTCOME MEASURES: Incidence of breast cancer before (at age <50 years) and after (> or = 50 years) the menopause. RESULTS: Size at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed > or =4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed <3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P=0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women. CONCLUSIONS: Size at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged <50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer.

Adult↗
PubMed2001

Changes in life expectancy in Russia in the mid-1990s.

BACKGROUND: Between 1987 and 1994, life expectancy in Russia declined substantially. Between 1994 and 1998, this trend reversed, and mortality rates returned to those of the early 1980s. Although the decline in life expectancy has been examined previously, much less is known about the subsequent improvement in mortality rates. We used recently published cause-specific mortality data up to 1998 to clarify this issue. METHODS: Changes in cause-specific death rates at ages 15-74 years were examined. Rates for 1998 were compared with those for 1994 (the year of lowest life expectancy) and for 1991 (the year the Soviet Union broke up). FINDINGS: Death rates among children fell steadily throughout the 1990s, and those in elderly people changed little. The reduction in mortality since 1994 was mainly due to a decrease in the death rate among middle-aged adults, which had increased until 1994. Deaths among those aged 15-30 years, which rose during 1991-94, remained high. Some causes of death, such as stomach cancer and road-traffic accidents, declined throughout the 1990s, whereas others, such as breast and prostate cancers and tuberculosis, increased. The decline in mortality since 1994 was, however, mainly due to a reduction in the rate of deaths from a group of causes associated with alcohol consumption. INTERPRETATION: The changing life expectancy in Russia is a consequence of a complex pattern of trends in different causes of death, some of which have their origins long in the past, and others that result from contemporary circumstances. This study provides further support for the view that alcohol has played an important part in the fluctuations in life expectancy in Russia in the 1990s, although there remains a need for a much better understanding of the factors underlying these continuing changes.

Adolescent↗
PubMed2001

The foetal origins of adult disease: interpreting the evidence from twin studies.

Twin studies have a contribution to make to the debate concerning the foetal origins of adult disease. Twins are growth retarded compared to singletons and experience post-natal catch-up growth. However, there is no evidence that twins are at increased risk of cardiovascular disease. Studying whether discordance in size at birth within monozygotic twin pairs is predictive of discordance in later life disease should help resolve whether the association between size at birth and later disease is due to common genetic factors. Results from studies of blood pressure in childhood and adult life looking at these within twin effects are far from conclusive. There are, however, methodological problems in the interpretation of these results, not least of which is the relatively small numbers of twin pairs studied. Studies exploring the effect of zygosity and chorion type on later disease provide may provide a useful extension of the research agenda. In summary, twin studies to date have raised more questions about the foetal origins hypothesis than they have resolved.

Adult↗
PubMed2001

Do socioeconomic disadvantages persist into old age? Self-reported morbidity in a 29-year follow-up of the Whitehall Study.

OBJECTIVES: This study examined (1) the relation of employment grade in middle age to self-reported poor health and functional limitations in old age and (2) whether socioeconomic status at approximately the time of retirement modifies health differentials in old age. METHODS: Survivors of the Whitehall Study cohort of men were resurveyed. Respondents were aged 40 to 69 years when they were originally screened in 1967 to 1970. RESULTS: Compared with senior administrators, men in clerical or manual (low-grade) jobs in middle age had quadruple the odds of poor physical performance in old age, triple the odds of poor general health, and double the odds of poor mental health and disability. At most, 20% of these differences were explained by baseline health or risk factors. Men who moved from low to middle grades before retirement were less likely than those who remained in low grades to have poor mental health. CONCLUSIONS: Socioeconomic status in middle age and at approximately retirement age is associated with morbidity in old age.

Activities of Daily Living↗
PubMed2000

Consequences of cAMP-binding site mutations on the structural stability of the type I regulatory subunit of cAMP-dependent protein kinase.

The regulatory (R) subunit of cAMP-dependent protein kinase (cAPK) is a multidomain protein with two tandem cAMP-binding domains, A and B. The importance of cAMP binding on the stability of the R subunit was probed by intrinsic fluorescence and circular dichroism (CD) in the presence and absence of urea. Several mutants were characterized. The site-specific mutants R(R209K) and R(R333K) had defects in cAMP-binding sites A and B, respectively. R(M329W) had an additional tryptophan in domain B. Delta(260-379)R lacked Trp260 and domain B. The most destabilizing mutation was R209K. Both CD and fluorescence experiments carried out in the presence of urea showed a decrease in cooperativity of the unfolding, which also occurred at lower urea concentrations. Unlike native R, R(R209K) was not stabilized by excess cAMP. Additionally, CD revealed significant alterations in the secondary structure of the R209K mutant. Therefore, Arg209 is important not only as a contact site for cAMP binding but also for the intrinsic structural stability of the full-length protein. Introducing the comparable mutation into domain B, R333K, had a smaller effect on the integrity and stability of domain A. Unfolding was still cooperative; the protein was stabilized by excess cAMP, but the unfolding curve was biphasic. The R(M329W) mutant behaved functionally like the native protein. The Delta(260-379)R deletion mutant was not significantly different from wild-type RIalpha in its stability. Consequently, domain B and the interaction between Trp260 and cAMP bound to site A are not critical requirements for the structural stability of the cAPK regulatory subunit.

Binding Sites↗
PubMed2000

Gestational age and growth rate of fetal mass are inversely associated with systolic blood pressure in young adults: an epidemiologic study of 165,136 Swedish men aged 18 years.

The objective of this study was to identify specific components of fetal growth that may underlie the observed association between birth weight and later blood pressure. A record linkage was made between the Swedish Medical Birth Registry, the Military Conscription Register, and censuses. For 165,136 men born in Sweden between 1973 and 1976 and conscripted from 1990 to 1996, systolic blood pressure was measured at age 18 years. Systolic pressure was independently inversely associated with birth weight for gestational age and with gestational age itself but not with birth length for gestational age. The difference in systolic pressure between the top and the bottom quintiles of birth weight for gestational age was -1.61 mmHg (95% confidence interval: -1.82 to -1.40) after adjustment for birth length for gestational age, height, and weight. The change in systolic pressure was -0.25 mmHg (-0.29 to -0.22) for a 1-week increase in gestational age. How far the inverse association of systolic pressure with length of gestation represents an independent effect of maturation is unclear. These findings help to refine the fetal origins hypothesis and provide further criteria against which potential biological mechanisms that link circumstances in utero to later blood pressure can be assessed.

Adolescent↗
PubMed2000

Probing the multidomain structure of the type I regulatory subunit of cAMP-dependent protein kinase using mutational analysis: role and environment of endogenous tryptophans.

The regulatory R-subunit of cAMP-dependent protein kinase (cAPK) is a thermostable multidomain protein. It contains a dimerization domain at the N-terminus followed by an inhibitor site that binds the catalytic C-subunit and two tandem cAMP-binding domains (A and B). Two of the three tryptophans in the RIalpha subunit, Trp188 and Trp222, lie in cAMP-binding domain A while Trp260 lies at the junction between domains A and B. The unfolding of wild-type RIalpha (wt-RI), monitored by intrinsic fluorescence, was described previously [Leon, D. A., Dostmann, W. R. G., and Taylor, S. S. (1991) Biochemistry 30, 3035 (1)]. To determine the environment of each tryptophan and the role of the adjacent domain in folding and stabilization of domain A, three point mutations, W188Y, W222Y, and W260Y, were introduced. The secondary structure of wt-RI and the point mutants has been studied by far-UV circular dichroism spectropolarimetry (CD). The CD spectra of wt-RI and the three point mutants are practically identical, and the thermal unfolding behavior is very similar. Intrinsic fluorescence and iodide quenching in the presence of increasing urea established that: (a) Trp222 is the most buried, whereas Trp188 is the most exposed to solvent; (b) Trp260 accounts for the quenching of fluorescence when cAMP is bound; and (c) Trp222 contributes most to the intrinsic fluorescence of the wt-RI-subunit, while Trp188 contributes least. For wt-RI, rR(W188Y), and rR(W260Y), removal of cAMP causes a destabilization, while excess cAMP stabilizes these three proteins. In contrast, rR(W222Y) was not stabilized by excess cAMP.

Circular Dichroism↗
PubMed2000

Wood dust exposure and cancer incidence: a retrospective cohort study of furniture workers in Estonia.

BACKGROUND: Occupational wood dust exposure is associated with increased risk of sinonasal cancer in men. However, little is known whether it is associated with sinonasal cancer in women or with malignancies of other sites. METHODS: In a retrospective cohort study of furniture workers, cancer incidence in 3723 men and 3063 women between 1968 and 1995 was compared to the incidence in the general population of Estonia. Cancer risks were analyzed by employment duration and occupation. RESULTS: The standardized incidence ratio (SIR) for all cancers did not differ significantly from one. Two men and one woman had sinonasal cancer (expected 1.07 and 0.53, respectively). Significantly increased risk of colon cancer was seen in the cohort (SIR 1.65, 95% confidence interval (CI) 1.22-2.17). Subjects employed for 10 years and over had significant excess of colon cancer (SIR 2.29, 95% CI 1.28-3.77) and rectal cancer (SIR 2.10, 95% CI 1.05-3.76) in the analysis by employment duration using exposure with a latency of 20 years. The nonsignificant excess of pharyngeal cancer in men (SIR 1.82) and lung cancer in women (SIR 1.43) was restricted to short-term workers. CONCLUSIONS: This study found an excess of colon and rectal cancer in furniture workers. There was no increase in total cancer risk.

Adult↗
PubMed2000

Social determinants of birthweight and length of gestation in Estonia during the transition to democracy.

BACKGROUND: To investigate social variation in birthweight and length of gestation in Estonia in the period of transition to a democracy and market economy. METHODS: All live births resulting from singleton pregnancies reported to the Estonian Medical Birth Registry in 1992-1997 (n = 84, 629) were studied with respect to social variation in birthweight and preterm delivery (<37 weeks gestation). The results were adjusted for maternal age, parity, education, nationality, marital status, smoking in pregnancy, sex of the infant (and gestational age). RESULTS: Between 1992 and 1997, mean birthweight increased from 3,465g to 3,497g (P < 0.001) and the preterm rate fell from 5.8% to 5.1% (P = 0.001). Maternal education, marital status and nationality were all independently related to the mean birthweight and the risk of preterm birth. The mean difference in birthweight between children of mothers with basic and university education was 87 g (95% CI : 74-100). Children born to mothers of non-Estonian compared to Estonian nationality were on average 77 g lighter (95% CI: 70-84). While the effect of nationality and marital status on birthweight was relatively stable during the study period, differences in birth outcome by maternal education became stronger. CONCLUSIONS: The mean birthweight increased and the preterm rate decreased in Estonia as a whole during the transition. However, the improvements were not shared equally by all social groups. An increase in variation in birthweight by maternal education was particularly notable.

Adolescent↗