Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of ...circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.
Th obese (ob) gene isolated from ob/ob mice in 1994 is expressed specifically in adipose tissue. The gene product, leptin, regulates food intake, energy expenditure and puberty. Reported herein is a ...2477 bp mRNA sequence for the pig obese gene, which includes the complete coding sequence. Two different ob cDNAs were identified, which differed by the inclusion or exclusion of a single glutamine codon at position +49 of the protein sequence. The pig obese gene encodes a 4.5 kb mRNA transcript, which is specific to adipose tissue. Southern blot analysis of fat and lean pigs showed a DNA polymorphism related to the lean phenotype. Differences in leptin mRNA levels showed that fat pigs have a higher level of leptin mRNA than lean pigs. These findings indicate that pig leptin expression can be associated with subcutaneous fat accumulation in pigs.
This article describes a family-based HIV prevention and mental health promotion program specifically designed to meet the needs of perinatally-infected preadolescents and their families. This ...project represents one of the first attempts to involve perinatally HIV-infected youth in HIV prevention efforts while simultaneously addressing their mental health and health care needs. The program, entitled CHAMP+ (Collaborative HIV Prevention and Adolescent Mental Health Project-Plus), focuses on: (1) the impact of HIV on the family; (2) loss and stigma associated with HIV disease; (3) HIV knowledge and understanding of health and medication protocols; (4) family communication about puberty, sexuality and HIV; (5) social support and decision making related to disclosure; and (6) parental supervision and monitoring related to sexual possibility situations, sexual risk taking behavior and management of youth health and medication. Findings from a preliminary evaluation of CHAMP+ with six families are presented along with a discussion of challenges related to feasibility and implementation within a primary health care setting for perinatally infected youth.
A key fatty acid synthesis enzyme, acetyl-CoA carboxylase alpha (ACC-alpha), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with ...the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-alpha common genetic variation (allele frequency >5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotype-tagging polymorphisms efficiently capturing common variation within 325 kb of ACC-alpha and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis.
Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of ...circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.
The Northern blot technique was used for mRNA phenotyping of 19 growth factors, ligands, receptors, and proteins involved in lipid metabolism in two populations of pigs with different fat deposition ...capabilities. The mRNA levels were measured in backfat, liver, and muscle tissue at different slaughter weights, taking backfat thickness, gender and breed of the animals into consideration. Of all the RNA patterns measured in the Landrace population, only the mRNA transcript level of low density lipoprotein receptor-related protein (also called alpha 2-macroglobulin receptor) was associated with the pig's backfat thickness phenotype in muscle and backfat tissues. In the population composed of purebred Yorkshire and Hampshire, epidermal growth factor receptor, malic enzyme, platelet derived growth factor beta and insulin-like growth factor binding protein 3 show different mRNA patterns associated with backfat thickness phenotypes. When analyzing the data using the gender or the breed as the main effect, the insulin receptor and insulin-like growth factor binding protein 1 were different between genders whereas insulin-like growth factor binding protein 3, malic enzyme, epidermal growth factor receptor and low density lipoprotein receptor-related protein were different between breeds. Analysis of this type should be helpful in understanding the regulation of fat deposition.
A large family of energetic salts were made using methylene bisoxyamine, CH
2
(-o-NH
2
)
2
, a dibasic, geminal oxyamine of methane. Single salts including the nitrate, perchlorate, dinitramide, and ...nitroformate, and doubly protonated methylene bisoxyamine salts, nitrate, perchlorate and bisdinitramide, were all synthesized in good to high yields, from simple acid-base reactions with the corresponding aciforms of energetic anions. All of the salts were characterized by vibrational (IR, Raman), multinuclear nmr (
1
H,
13
C), and DSC studies. The single crystal X-ray diffraction study was carried out on the double perchlorate salt. Initial safety studies (impact and friction), were carried out on most of the new materials, as well as the thermal stability of these salts at 75°C.
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