PubMed Health⌕ Search

Biomedical subjects

W Hale

Publications and source records attributed to W Hale.

16 recordsLinked to original sources

Genome-wide responses to mitochondrial dysfunction.

Mitochondrial dysfunction can lead to diverse cellular and organismal responses. We used DNA microarrays to characterize the transcriptional responses to different mitochondrial perturbations in Saccharomyces cerevisiae. We examined respiratory-deficient petite cells and respiratory-competent wild-type cells treated with the inhibitors of oxidative phosphorylation antimycin, carbonyl cyanide m-chlorophenylhydrazone, or oligomycin. We show that respiratory deficiency, but not inhibition of mitochondrial ATP synthesis per se, induces a suite of genes associated with both peroxisomal activities and metabolite-restoration (anaplerotic) pathways that would mitigate the loss of a complete tricarboxylic acid cycle. The array data suggested, and direct microscopic observation of cells expressing a derivative of green fluorescent protein with a peroxisomal matrix-targeting signal confirmed, that respiratory deficiency dramatically induces peroxisome biogenesis. Transcript profiling of cells harboring null alleles of RTG1, RTG2, or RTG3, genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast.

Antimycin A↗

MAD: a suite of tools for microarray data management and processing.

SUMMARY: Microarray data management and processing (MAD) is a set of Windows integrated software for microarray analysis. It consists of a relational database for data storage with many user-interfaces for data manipulation, several text file parsers and Microsoft Excel macros for automation of data processing, and a generator to produce text files that are ready for cluster analysis. AVAILABILITY: Executable is available free of charge on http://pompous.swmed.edu. The source code is also available upon request.

Databases, Factual↗

Hand-held computers for family physicians.

Hand-held computers such as the Apple Newton MessagePad, HP 200LX, Psion 3a, and Franklin DBS-2 are now powerful enough to be useful to family physicians in their care of patients. Each fits in a laboratory coat pocket, weighs a pound or less, costs less than $700, turns on instantly, and has excellent battery life. A wide variety of software, including computerized medical records, medical calculators, and medical references, is available.

Family Practice↗

Gallbladder prostaglandins and lysophospholipids as mediators of mucin secretion during cholelithiasis.

Mucin hypersecretion from the gallbladder epithelium contributes to cholesterol gallstone formation by accelerating the nucleation of cholesterol-supersaturated bile. Prostaglandins (PGs) and lysophosphatidylcholine (LPC) have both been implicated as potential mediators of mucin hypersecretion, but their roles are unclear. We fed prairie dogs a lithogenic diet (0.34% cholesterol), and after 1, 2, 4, or 6 wk of cholesterol feeding, we measured glycoprotein and LPC concentrations in bile and PG synthesis in gallbladder and liver slices. Hypercholesterolemia and cholesterol supersaturation of bile occurred after 1 wk of cholesterol feeding, but marked crystal formation was delayed until 4 wk, when glycoprotein concentrations became markedly elevated. Glycoprotein hypersecretion was preceded by increased synthesis of PGF2 alpha (P less than 0.002), PGE2 (P less than 0.001), prostacyclin (P less than 0.05), and thromboxane (P = 0.07) in the gallbladder after only 2 wk of cholesterol feeding, but PG synthesis in the liver remained unchanged (P greater than 0.14). LPC concentrations in gallbladder bile also increased at 2 wk (P less than 0.02), but LPC in hepatic bile was unchanged (P = 0.35). In organ culture studies, LPC caused a dose-dependent stimulation of [3H]glycoprotein release from guinea pig gallbladder mucosa that could not be explained solely by LPC's detergent properties. We conclude that gallbladder PG synthesis and LPC production are increased at an early stage of cholesterol gallstone formation in the prairie dog model. These changes probably play a significant role in gallstone pathogenesis, since they mediate hypersecretion of gallbladder mucin and thus favor the nucleation of cholesterol-supersaturated bile.

Animals↗