A comparative study of specific nuclear binding of estrogen in some target and nontarget organs of rats

When this research project was initiated, my advisor, Dr. David Maxwell, said to me, “Freda, good research answers one question and asks ten more.” Thus, we prepared to test our hypothesis regarding specific nuclear binding of estrogen in four organs of the laboratory rat. Based on information obtained from studies involving estrogen binding in the uterus, spleen, liver and large intestine, we hypothesized that the uterus, a well known target organ for estrogen, would have a high degree of specific nuclear binding. The large intestine, for which no evidence was found that implicated it as a target organ, would characteristically have a small amount of specific nuclear estrogen binding. The liver and spleen are two possible target organs. More substantial research has been found that implicates the liver as a target organ than has been found implicating the spleen, so we expected to find a degree of specific binding in the liver somewhat less than the uterus, but significantly greater than the large intestine. The spleen, while it is a controversial organ does not seem to be as good a candidate for a target organ as the liver--at least not at the present--so we expected specific nuclear binding to be less than the liver but still significantly greater than the large intestine. This states the hypothesis of this paper and what we expect to see in the results. The remainder of the paper concerns itself with giving background information about estrogen and estrogen binding, with a statement of the procedure used to test the hypothesis and the results of that test

Genes Involved in the Metabolism of Poly-Unsaturated Fatty-Acids (PUFA) and Risk for Crohn's Disease in Children & Young Adults

Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD.A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10) genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD) age of the cases was 12.4 (±3.3) years. Most cases were male (56.4%), had ileo-colonic disease (L3±L4, 52.7%) and inflammatory behavior (B1±p, 87%) at diagnosis. One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG) (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR (recessive) = 0.56, 95% CI = 0.35-0.89; p = 0.01), rs2074902 (OR (trend) = 1.26, 95% CI = 1.00-1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00-2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) = 0.58, 95% CI = 0.30-1.13; p = 0.10) showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99-1.67; p = 0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0.14).Inherited variation in enzymes involved in the synthesis/metabolism of LTB(4) may be associated with CD. These findings implicate PUFA metabolism as a important pathway in the CD pathogenesis