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51.
Few studies have examined the effects of both prenatal and postnatal growth on hypertension. We report on hypertension in 2003 people aged 62 years who were randomly selected from the Helsinki birth cohort and examined in a clinic. Their heights and weights had been recorded serially up to age 11 years. A total of 644 had already been diagnosed with hypertension. Compared with normotensive people, they were obese and insulin resistant. At birth they were thin and short, and they gained weight slowly up to age 2 years; thereafter they grew rapidly so that at age 11 years their body size was around the average. The odds ratio associated with each kilogram of birthweight was 0.42 (95% CI: 0.32 to 0.56); with each 10 kg of current weight it was 1.85 (95% CI: 1.66 to 2.05). The blood pressures of another 802 people were classified as hypertensive under current definitions. They were overweight and had an atherogenic lipid profile. At birth they were short, and after birth they grew slowly so that at age 11 years they were short and thin. The odds ratio associated with each kilogram of weight at age 2 years was 0.75 (95% CI: 0.68 to 0.84); with each 10 kg of current weight it was 1.42 (95% CI: 1.28 to 1.57). We conclude that 2 different paths of childhood growth precede the development of hypertension. We suggest that they lead to hypertension through different biological mechanisms and may respond differently to medication. 相似文献
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Painter RC de Rooij SR Bossuyt PM Simmers TA Osmond C Barker DJ Bleker OP Roseboom TJ 《The American journal of clinical nutrition》2006,84(2):322-7; quiz 466-7
BACKGROUND: Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring. OBJECTIVE: We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery disease (CAD). DESIGN: We compared the age at onset and cumulative incidence of CAD between persons born as term singletons who were exposed to the 1944-1945 Dutch famine during late (n = 160), mid- (n = 138), or early (n = 87) gestation and 590 unexposed subjects at age 50 or 58 y. Age at CAD onset was defined as the age at which angina pectoris was identified (according to the Rose questionnaire), Q waves were observed on an electrocardiogram (Minnesota codes 1-1 or 1-2), or coronary revascularization was performed (by angioplasty or bypass surgery). RESULTS: Of the 83 CAD cases identified, persons conceived during the famine were 3 y younger than the unexposed persons at the time of CAD diagnosis (47 y compared with 50 y) and had a higher cumulative incidence of CAD [13%; hazard ratio (HR) adjusted for sex: 1.9; 95% CI: 1.0, 3.8] than did the unexposed persons. The HR changed little after adjustment for smoking (HR: 1.8), social class (HR: 2.0), or size at birth (HR: 2.0). CONCLUSIONS: We found an earlier onset of CAD among persons conceived during the famine, which suggests that maternal nutrition in early gestation may play a role in the onset of CAD. This finding agrees with evidence from animal experiments that identify periconceptional maternal diet as important in the offspring's adult health. 相似文献
55.
Fetal growth and impaired glucose tolerance in men and women 总被引:12,自引:0,他引:12
K. Phipps D. J. P. Barker C. N. Hales C. H. D. Fall C. Osmond P. M. S. Clark 《Diabetologia》1993,36(3):225-228
Summary A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition. 相似文献
56.
The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= ?0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = ?0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= ?0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance. 相似文献
57.
Population Dynamics of Bone Marrow B Lymphocytes 总被引:29,自引:0,他引:29
58.
Lam QL Lo CK Zheng BJ Ko KH Osmond DG Wu GE Rottapel R Lu L 《International immunology》2007,19(3):267-276
Previous studies on c-Abl-deficient mice have shown high post-natal mortality and lymphopenia. However, the mechanisms by which c-Abl may influence B lymphopoiesis remain obscure. In this study, we analyzed B cell sub-populations at various differentiation stages in the bone marrow (BM) of c-Abl-deficient mice. Phenotypic analyses revealed that c-Abl(-/-) pro-B cells were reduced to half of normal incidence and absolute number, while pre-B cells showed an even greater reduction. Both c-Abl(-/-) pro-B and pre-B cell populations showed considerably elevated apoptosis ex vivo and in short-term culture but their cell cycle progression was not impaired. In contrast, apoptosis of immature IgM(+)IgD(-) B lymphocytes remained at normal control levels. Inhibition of c-Abl activity by STI571 in normal BM cultures significantly increased apoptosis in B cell precursors while the survival of immature B cells was not affected. To determine whether c-Abl deficiency affects Ig heavy-chain rearrangement, we found that the frequency of V(D)J recombination was markedly reduced by 15-fold in c-Abl(-/-) pro-B cells compared with the control values. However, no perturbation in the levels of signal-end recombination intermediates was found. Taken together, we propose that c-Abl mediates a stage-specific anti-apoptotic response in precursor B cells and is required for efficient V(D)J recombination during B cell development. 相似文献
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