Biomedical subjects

Douglas A Powell

Publications and source records attributed to Douglas A Powell.

6 recordsLinked to original sources

PubMed2003

Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(II).

Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix.

Algorithms↗

PubMed2003

VIRTUAL2D: A web-accessible predictive database for proteomics analysis.

The available archive of sequence databases compiled from whole genome projects and budding proteomics efforts have enabled us to develop VIRTUAL2D, an interactive system for the assembly of virtual protein expression maps computed on the basis of theoretical isoelectric focusing point, molecular weight, tissue specificity and relative abundance for any set of proteins currently catalogued. This tool will assist in the preliminary, albeit putative, prediction of the identity and location of unknown and/or low abundance proteins in experimentally derived two-dimensional polyacrylamide gel electrophoresis maps.

Amino Acids↗

PubMed2003

Implementation and analysis of an on-farm food safety program for the production of greenhouse vegetables.

Fresh fruits and vegetables are increasingly being recognized as vectors for foodborne illness. In 1998, an on-farm food safety program was developed for the Ontario Greenhouse Vegetable Growers (OGVG) in Ontario, Canada. This hazard analysis critical control point-based system was designed to reduce the potential of microbial contamination along the entire production and distribution process. A previous report (D. A. Powell, M. Bobadilla-Ruiz, A. Whitfield, M. W. Griffiths, and A. Luedtke, J. Food Prot. 65:918-923) outlined the first 2 years of the program; the present report documents the third year of the program's implementation. Through individual on-site grower visits and the microbiological testing of produce and water, the program's OGVG member requirements were determined, and the program's success was assessed. Growers' knowledge, understanding, and awareness of microbial risks associated with fresh produce have increased, and improvements in practices used in greenhouses and packing sheds were noted.

Agriculture↗

PubMed2002

Multidrug-resistance mdr1a/1b double knockout mice are more sensitive than wild type mice to acute arsenic toxicity, with higher arsenic accumulation in tissues.

Arsenic is an environmental toxicant. Active extrusion via the ArsAB pump is a mechanism for arsenic detoxication in bacteria. However, how arsenic is effluxed from mammalian cells is not completely known. Our recent work shows that acquired arsenic resistance is associated with overexpression of P-glycoprotein and can be reversed by PSC833, an inhibitor for P-glycoprotein. This study utilized the mdr1a/1b(-/-) mice, which lack mdr1-type P-glycoproteins, to examine whether these mice are sensitive to arsenic toxicity and have higher arsenic accumulation in their tissues. The mdr1a/1b(-/-) and wild-type FVB mice were given arsenic as sodium arsenite (12-19 mg/kg, sc) and toxicity was examined 24 h later. The mdr1a/1b(-/-) mice were more sensitive than wild-type mice to arsenite-induced lethality, with LD(50) of 14.5 and 17 mg/kg, respectively. Histologically, arsenite produced more frequent and more severe lesions in the liver and kidney of the mdr1a/1b(-/-) mice than in wild-type mice. Serum alanine aminotransferase activity and blood urea nitrogen levels, indicative of hepatic and renal damage respectively, were increased 4 to 6-fold in the mdr1a/1b(-/-) mice as compared with 1-2-fold increases in wild-type mice. The mdr1a/1b(-/-) mice accumulated more arsenic in the liver (15.3 vs. 5.2 microg/g), kidney (7.23 vs. 3.22 microg/g), small intestine (3.98 vs. 1.57 microg/g) and brain (0.45 vs. 0.17 microg/g), as compared with wild-type mice 24 h after sodium arsenite (14 mg/kg, s.c.) administration. In summary, this study demonstrated that the mdr1a/1b(-/-) mice were more sensitive to acute arsenic toxicity and accumulated more arsenic than wild-type mice, suggesting that P-glycoproteins are involved, at least in part, in arsenic efflux in mammalians.

Alanine Transaminase↗

PubMed2002

Robustness of the Chen-Dougherty-Bittner procedure against non-normality and heterogeneity in the coefficient of variation.

Chen, Dougherty, and Bittner [Y. Chen, E. R. Dougherty, and M. L. Bittner, J. Biomed. Opt. 2(4), 364-374 (1997)] provided the derivation of a probability density function (PDF) for a signal ratio from a DNA microarray. This PDF is potentially useful for testing whether a pair of signals from the same gene has a common mean. The derivation of the PDF assumes the normality of all signal distributions and a common coefficient of variation (CV) for all signals within a microarray. The testing procedure requires the calculation of a common confidence interval for a microarray, based on a maximum likelihood estimator of the "common" CV, and the determination of whether or not a ratio for a particular gene falls within this interval. This study used Monte Carlo techniques and demonstrated that the procedure is robust to violations of normality and also to constancy in the coefficients of variation. A closer examination of the dynamics of the procedure found that the robustness was the result of offsetting effects. The size of the confidence interval was increased as a result of higher estimates of the common CV, as the actual CV pattern became heterogeneous. This effect mitigated the inflation in the size of the ratio as a result of increasing CV heterogeneity. These findings suggest that the Chen-Dougherty-Bittner procedure may be used even if underlying assumptions do not hold.

Analysis of Variance↗

PubMed2002

Development, implementation, and analysis of an on-farm food safety program for the production of greenhouse vegetables.

Fresh fruits and vegetables are increasingly recognized as vectors for foodborne illness. Consequently, an on-farm food safety program was developed, implemented, and analyzed for the Ontario Greenhouse Vegetable Growers in Ontario, Canada, during a 2 1/2-year period. This hazard analysis critical control point-based system was designed to reduce the potential of microbial contamination along the entire production and distribution process. Through the use of microbiological testing, on-site visits, and producer surveys, it was determined that the program has increased grower knowledge, understanding, and awareness of microbial risks associated with fresh produce and caused improvements in practices used within the greenhouse and packing sheds.

Agriculture↗