Allelic variation in the size of the insulin (INS) variable number tandem repeat (VNTR) correlates with the expression of both INS in the pancreas and thymus and IGF2 (the gene downstream of INS)in the placenta. In addition, the shorter, class I alleles are associated with type 1 diabetes, whereas the longer, class III alleles are associated with type 2 diabetes, polycystic ovary syndrome (PCOS), and size at birth. Parent-of-origin effects have been reported for type 2 diabetes and PCOS, thus implicating a role for genomic imprinting in these phenotypes. In mice, Ins2 is imprinted and paternally expressed in the yolk sac. In humans, evidence for the imprinting of INS is circumstantial, with occasional monoallelic expression in the thymus. In the present study, we found evidence for the imprinted paternal expression of INS in the human yolk sac. Two other imprinted genes from the same cluster are also expressed monoallelically in the human yolk sac. IGF2 was expressed solely from the paternal allele, and H19 was expressed solely from the maternal allele. These data suggest not only further functional roles for the human yolk sac in early fetal growth, but also evidence for a potential causal link between the control of insulin expression during development and insulin/growth-related diseases in later life. Diabetes 50: [199][200][201][202][203] 2001 A llelic variation at the insulin (INS) variable number tandem repeat (VNTR) is known to regulate the level of expression of both INS in the pancreas and thymus and IGF2 in the placenta (1-5). The shorter, class I alleles correlate with levels of gene expression that are higher for INS in the pancreas, lower for INS in the thymus, and higher for IGF2 in the placenta. Higher levels of INS expression associated with the longer, class III VNTR alleles in the thymus offer an explanation for the protective role of these alleles in type 1 diabetes susceptibility by inducing self-tolerance to preproinsulin peptides (1,2). The class I alleles are associated with type 1 diabetes, and the class III alleles are associated with type 2 diabetes, polycystic ovary syndrome (PCOS), and size at birth (5-10). In PCOS and type 2 diabetes, disease susceptibility is conferred in a parental sex-specific fashion (6,9), such that in nuclear families, the susceptible allele is transmitted preferentially from fathers. This suggests that the etiological effect is occurring when only the paternal allele is active, implicative of parental imprinting. Although the imprinting of IGF2 is well established (11), evidence for monoallelic expression of insulin comes only from mice, in which Ins2 (the mouse ortholog of INS) is imprinted in the yolk sac after 14.5 days (12,13). In mammals, the secondary yolk sac is regarded as being the primitive liver, involved in protein synthesis and nutrient transfer and acting as a stem-cell reservoir (14,15). The secondary yolk sac may also play a role as a primitive pancreas, because in the fourth week of development, the yolk sac forms the primitive gut, the en...
Objectives To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. Design An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. Setting England. Population Individuals eligible for the National Chlamydia Screening Programme. Main outcome measures Cost effectiveness of National Chlamydia Screening Programme in 2008-9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions-(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. Results In 2008-9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. Conclusions In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely to cost less than increasing male coverage but also improve the ratio of women to men diagnosed. Further evaluation of the cost effectiveness of partner notification and screening is urgently needed. The spreadsheet tool developed in this study can be easily modified for use in other settings to evaluate chlamydia control programmes.
Between 22 January and 4 April 1997, 467 hepatitis A cases were reported to the New South Wales Health Department, Australia. To identify the cause of the outbreak, we conducted a matched case-control study, and an environmental investigation. Among 66 cases and 66 postcode-matched controls, there was a strong association between illness and consumption of oysters (adjusted odds ratio 42; 95 % confidence interval 5-379). More than two-thirds of cases reported eating oysters, including one third of cases and no controls who reported eating oysters in the Wallis Lake area. A public warning was issued on 14 February, and Wallis Lake oysters were withdrawn from sale. Hepatitis A virus was subsequently identified in oyster samples taken from the lake. Hepatitis A virus poses a special risk to consumers who eat raw oysters because it can survive for long periods in estuaries and cause severe disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.