Reliability of maternal-reports regarding the use of household pesticides: experience from a case-control study of childhood leukemia

Introduction: Self-reported household pesticide use has been associated with higher risk of childhood leukemia in a number of case–control studies. The aim of this study is to assess the reliability of self-reported household use of pesticides and potential differences in reliability by case–control status, and by socio-demographic characteristics. Methods: Analyses are based on a subset of the Northern California Childhood Leukemia Study population. Eligible households included those with children less than 8 years old who lived in the same residence since diagnosis (reference date for controls). The reliability was based on two repeated in-person interviews. Kappa, percent positive and negative agreements were used to assess reliability of responses to ever/never use of six pesticides categories. Results: Kappa statistics ranged from 0.31 to 0.61 (fair to substantial agreement), with 9 out of the 12 tests indicating moderate agreement. The percent positive agreement ranged from 46 to 80% and the percent negative agreement from 54 to 95%. Reliability for all pesticide types as assessed by the three reliability measures did not differ significantly for cases and controls as confirmed by bootstrap analysis. For most pesticide types, Kappa and percent positive agreement were higher for non-Hispanics than Hispanics and for households with higher income vs. lower income. Conclusions: Reproducibility of maternal-reported pesticide use was moderate to high and was similar among cases and controls suggesting that differential recall is not likely to be a major source of bias.     

GABAA receptor subtypes immunopurified from rat brain with alpha subunit-specific antibodies have unique pharmacological properties.

The unique cytoplasmic loop regions of the alpha 1, alpha 2, alpha 3, and alpha 5 subunits of the GABAA receptor were expressed in bacterial and used to produce subunit-specific polyclonal antisera. Antibodies immobilized on protein A-Sepharose were used to isolate naturally occurring alpha-specific populations of GABAA receptors from rat brain that retained the ability to bind [3H]muscimol, [3H]flunitrazepam, [3H]Ro15-1788, and [125I]iodo-clonazepam with high affinity. Pharmacological characterization of these subtypes revealed marked differences between the isolated receptor populations and was generally in agreement with the reported pharmacological profiles of GABAA receptors in cells transiently transfected with alpha 1 beta 1 gamma 2, alpha 2 beta 1 gamma 2, alpha 3 beta 1 gamma 2, and alpha 5 beta 1 gamma 2 combinations of subunits. Additional subtypes were also identified that bind [3H]muscimol but do not bind benzodiazepines with high affinity. The majority of GABAA receptor oligomers contains only a single type of alpha subunit, and we conclude that alpha 1, alpha 2, alpha 3, and alpha 5 subunits exist in vivo in combination with the beta subunit and gamma 2 subunit.     

Quantifying the Gurken morphogen gradient in Drosophila oogenesis

Quantitative information about the distribution of morphogens is crucial for understanding their effects on cell-fate determination, yet it is difficult to obtain through direct measurements. We have developed a parameter estimation approach for quantifying the spatial distribution of Gurken, a TGFalpha-like EGFR ligand that acts as a morphogen in Drosophila oogenesis. Modeling of Gurken/EGFR system shows that the shape of the Gurken gradient is controlled by a single dimensionless parameter, the Thiele modulus, which reflects the relative importance of ligand diffusion and degradation. By combining the model with genetic alterations of EGFR levels, we have estimated the value of the Thiele modulus in the wild-type egg chamber. This provides a direct characterization of the shape of the Gurken gradient and demonstrates how parameter estimation techniques can be used to quantify morphogen gradients in development.     

SYNTHESIS OF NOVEL BICYCLIC NUCLEOSIDES RELATED TO NATURAL GRISEOLIC ACIDS

Abstract

Synthesis of novel, bicyclic nucleosides related to natural griseolic acids is described. The synthetic approach involves nucleobase construction at the C-2′ position of 1,4:3,6-diandydro-D-mannitol. The carbohydrate precursor used in the synthesis, 1,4:3,6-dianhydro-D-glucitol, can be prepared easily from D-glucitol. Bicyclic analogues of five naturally occurring nucleosides have been prepared. The single crystal X-ray structure of a representative example is presented and discussed.     

Regulation of ciliary motility: conserved protein kinases and phosphatases are targeted and anchored in the ciliary axoneme

Recent evidence has revealed that the dynein motors and highly conserved signaling proteins are localized within the ciliary 9 + 2 axoneme. One key mechanism for regulation of motility is phosphorylation. Here, we review diverse evidence, from multiple experimental organisms, that ciliary motility is regulated by phosphorylation/dephosphorylation of the dynein arms through kinases and phosphatases that are anchored immediately adjacent to their axonemal substrates.     

Divergent effects of cyanate on amino acid and phosphate uptake by liver and hepatoma.

The uptake of alpha-aminoiso[3H]butyric acid and 32Pi was observed to be inhibited by sodium cyanate in transplanted hepatomas but was increased in the livers of the tumor bearing rats. Incorporation of 32Pi into macromolecules in hepatomas was also inhibited by cyanate. Treatment with this drug did not influence circulating concentrations of isotope-labeled materials. There were relatively small effects on uptake of 36Cl- in cyanate-treated rats and the action was not tissue specific. The data were compatible with an inhibitory effect of cyanate on active transport in hepatomas which was not seen under the same conditions in host liver.     

Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines

Taiwanese aborigines have a high prevalence of hyperuricemia and gout. Uric acid levels and urate excretion have correlated with dopamine-induced glomerular filtration response. MAOs represent one of the major renal dopamine metabolic pathways. We aimed to identify the monoamine oxidase A (MAOA, Xp11.3) gene variants and MAO-A enzyme activity associated with gout risk. This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 × 10^?5, adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11–1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28–2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with hyperuricemia and gout (P for trend = 2.00 × 10^?3 vs. normal control). We also found that MAOA enzyme activity by rs1137070 allele was associated with hyperuricemia and gout (P for trend = 1.53 × 10^?6 vs. wild-type allele). Thus, our results show that some MAOA alleles, which have a higher enzyme activity, predispose to the development of gout.