Color Doppler ultrasound evaluation of testicular blood flow in stallions

The objectives of this study were to evaluate the potential use of color Doppler ultrasound to characterize blood flow to the stallion testis, and to establish reference values for Doppler measures of blood flow in the testicular artery of the stallion. Both testes from each of 52 horses were examined using a pulsed-wave color Doppler ultrasound with a sector array 5/7.5 MHz transducer with a 1mm gate setting. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) of the testicular artery were measured in each of two locations, the convoluted aspect (spermatic cord) and the marginal aspect of the artery (on the epididymal edge of testis). We found that: (1) all measures were obtainable; (2) except for EDV, the majority of the measures were higher at the cord location than at the marginal aspect of the artery (P < 0.05); and (3) measures for left and right testes were similar (P > 0.10). Resulting measures from 41 of these stallions (82 testes) that appeared free of testicular pathology provide useful reference values for clinical evaluation. Evaluation of 11 cases with testicular pathology suggested further investigation of possible effects of these various conditions on testicular blood flow and testicular function.     

Determining meteorological drivers of salt marsh mosquito peaks in tropical northern Australia

In northern Australia the northern salt marsh mosquito Aedes vigilax is a vector of Ross River virus and is an appreciable pest. A coastal wetland adjacent to Darwin's residential suburbs offers a favorable habitat for Ae. vigilax, and despite vigilant mosquito control efforts, peaks of Ae. vigilax occur in excess of 500/trap/night some months. To improve mosquito control for disease and nuisance biting to nearby residential areas, we sought to investigate meteorological drivers associated with these Ae. vigilax peaks. We fitted a cross‐sectional logistic regression model to weekly counts of female Ae. vigilax mosquitoes collected between July, 1998 and June, 2009 against variables, tide, rainfall, month, year, and larval control. Aedes vigilax peaks were associated with rainfall during the months September to November compared with January, when adjusted for larval control and tide. To maximize mosquito control efficiency, larval control should continue to be implemented after high tides and with increased emphasis on extensive larval hatches triggered by rainfall between September and November each year. This study reiterates the importance of monitoring and evaluating service delivery programs. Using statistical modelling, service providers can obtain solutions to operational problems using routinely collected data. These methods may be applicable in mosquito surveillance or control programs in other areas.     

Structural requirements for high affinity ligand binding by estrogen receptors: a comparative analysis of truncated and full length estrogen receptors expressed in bacteria, yeast, and mammalian cells.

In order to better understand the structural requirements for effective high affinity binding of estrogens and antiestrogens by the human estrogen receptor (ER), a comparative study was undertaken in which we examined: 1) native ER from the MCF-7 ER-positive human breast cancer cell line; 2) full length ER expressed in yeast; 3) the ER hormone binding domain (amino acid residues 302-595) expressed in yeast; 4) a bacterially expressed protein A fusion product encoding a truncated ER (amino acid residues 240-595); and 5) a synthetic peptide encompassing amino acids 510-551 of the ER. The binding parameters studied included affinity, kinetics, structural specificity for ligands, and stability. Full length ER expressed in yeast was very similar to the MCF-7 ER in its affinity [dissociation constant (Kd), 0.35 +/- 0.05 nM], dissociation rate (t1/2, 3-4 h at 25 C), and structural specificity for both reversible and covalently attaching affinity ligands. While the truncated ER expressed in yeast was similar to MCF-7 ER in its specificity of ligand binding, it showed a slightly reduced affinity for estradiol (Kd, 1.00 +/- 0.17 nM). The bacterially expressed ER also had a lower affinity for estradiol (Kd, 1.49 +/- 0.16 nM), which may be due in part to an increase in the dissociation rate (t1/2, 0.5 h at 25 C). The attachment of covalent affinity ligands and structural specificity for a variety of reversible ligands was comparable in the bacterially expressed ER to that observed for the receptors expressed in MCF-7 cells and yeast.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility Loci

Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Brothers and sons of affected men have a 2-3-fold increased risk of developing prostate cancer. However, identification of genetic susceptibility loci for prostate cancer has been extremely difficult. Although the suggestion of linkage has been reported for many chromosomes, the most promising regions have been difficult to replicate. In this study, we compare genome linkage scans using microsatellites with those using single-nucleotide polymorphisms (SNPs), performed in 467 men with prostate cancer from 167 families. For the microsatellites, the ABI Prism Linkage Mapping Set version 2, with 402 microsatellite markers, was used, and, for the SNPs, the Early Access Affymetrix Mapping 10K array was used. Our results show that the presence of linkage disequilibrium (LD) among SNPs can lead to inflated LOD scores, and this seems to be an artifact due to the assumption of linkage equilibrium that is required by the current genetic-linkage software. After excluding SNPs with high LD, we found a number of new LOD-score peaks with values of at least 2.0 that were not found by the microsatellite markers: chromosome 8, with a maximum model-free LOD score of 2.2; chromosome 2, with a LOD score of 2.1; chromosome 6, with a LOD score of 4.2; and chromosome 12, with a LOD score of 3.9. The LOD scores for chromosomes 6 and 12 are difficult to interpret, because they occurred only at the extreme ends of the chromosomes. The greatest gain provided by the SNP markers was a large increase in the linkage information content, with an average information content of 61% for the SNPs, versus an average of 41% for the microsatellite markers. The strengths and weaknesses of microsatellite versus SNP markers are illustrated by the results of our genome linkage scans.     

LPS-induced biomarkers in mice: a potential model for identifying insulin sensitizers

The contribution of nutrient overload and associated inflammation to insulin resistance has highlighted several therapeutic targets including c-Jun N-terminal kinase (JNK) and S6 kinase (S6K). To investigate how a lipopolysaccharide (LPS)-mediated inflammatory response may modulate pathways implicated in insulin resistance, we characterized the LPS-induced changes in key biomarkers. Administration of 0.06-4 mg/kg LPS to C57BL/6 mice stimulated increases in plasma levels of TNFalpha, IL-12p40, IL-6 and MCP-1 and in JNK activity as measured by phosphorylated c-Jun in fat. For the first time, we show that LPS induces S6K activity by up to 6.1-fold, as measured by the phosphorylation of S6 ribosomal protein in liver, and increases by up to 1.8-fold, plasma levels of the novel pro-inflammatory cytokine osteopontin which is implicated in the pathogenesis of insulin resistance. These novel findings suggest that LPS administration may form the basis of an acute in vivo pharmacodynamic model for therapies targeting multiple pathways implicated in insulin resistance.