Biomedical subjects

R A Dennis

Publications and source records attributed to R A Dennis.

14 recordsLinked to original sources

PubMed2000

InternetQuestion and Answer (iQ&A): a Web-based survey technology.

This paper presents InternetQuestion and Answer, a Web-based survey development and implementation technology, which has been designed for constructing on-line surveys for educational, medical, or administrative purposes. The system, called iQ&A, is a three-tiered database-backed Web system that has been developed to support a wide range of applications. Surveys are considered as general data collection instruments and include a wide field of application. iQ&A facilitates rapid survey construction and administration which is ideally suited for biomedical research as well as other research and educational activities. Full report management capabilities provide the survey publisher on-line access to current information on survey responses. Current implementations of this technology in the areas of biomedical applications of clinical trials, longitudinal research, and other research-related systems are presented. Further refinement of the current system should lead to a powerful general survey technology for broad-based applications.

Data Collection↗

PubMed1999

Yeast mutants of glucose metabolism with defects in the coordinate regulation of carbon assimilation.

The enzymes of the glyoxylate cycle and gluconeogenesis are tightly regulated by transcriptional, posttranscriptional, and posttranslational mechanisms in Saccharomyces cerevisiae. We have previously identified four genes, ACN8, ACN9, ACN17, and ACN18, whose mutant phenotype includes two- to fourfold elevated levels of enzymes of the glyoxylate cycle, gluconeogenesis, and acetyl-CoA metabolism. The affected enzymes are elevated on nonfermentable carbon sources but are still fully repressed by glucose. Catabolite inactivation of the cytosolic malate dehydrogenase is not affected in the mutants. Instead, the phenotype appeared to be manifested primarily at the level of transcription. The ACN8, ACN17, and ACN18 genes were isolated by functional complementation of the respective mutant's inability to utilize acetate as a carbon and energy source, and these genes were shown to encode subunits of metabolic enzymes. ACN8 was identical to FBP1, which encodes the gluconeogenic enzyme, fructose 1,6-bisphosphatase, while ACN17 and ACN18 were identical to the SDH2 and SDH4 genes, respectively, that encode subunits of the respiratory chain and tricarboxylic acid cycle enzyme, succinate dehydrogenase. Mutants defective in other glyoxylate cycle and gluconeogenic enzymes also display the elevated enzyme phenotype, indicating that the enzyme superinduction is a general property of gluconeogenic dysfunction. Glucose 6-phosphate levels were diminished in the mutants, suggesting that endogenous glucose synthesis can regulate the expression of gluconeogenic enzymes.

Acetyl Coenzyme A↗

PubMed1999

Acn9 is a novel protein of gluconeogenesis that is located in the mitochondrial intermembrane space.

Previous studies have indicated that the Acn9 protein is involved in gluconeogenesis. Yeast mutants defective in the ACN9 gene display phenotypes identical with mutants defective in metabolic enzymes required for carbon assimilation. These phenotypes include the inability to utilize acetate as a carbon and energy source, elevated levels of enzymes of the glyoxylate cycle, gluconeogenesis and acetyl-CoA mobilization, and a deficiency in de novo synthesis of glucose from ethanol. The ACN9 gene was isolated by functional complementation of the acetate growth defect of an acn9 mutant. The open reading frame corresponds to YDR511w, and encodes a protein of unknown function. Homologs have been identified in human, mouse, and nematode databases. Two mutant alleles were sequenced. The mutations altered amino acid residues that are conserved among members of the new gene family. ACN9 gene expression was slightly repressed by glucose, and the level of the transcript was approximately 100-fold lower than that of glyoxylate or tricarboxylic acid cycle enzymes. A functional epitope-tagged form of Acn9 was expressed to study expression and the subcellular localization of the protein. The tagged protein was localized to the mitochondrial intermembrane space.

Amino Acid Sequence↗

PubMed1998

Genes of succinyl-CoA ligase from Saccharomyces cerevisiae.

Succinyl-CoA ligase (succinyl-CoA synthetase) catalyzes the nucleotide-dependent conversion of succinyl-CoA to succinate. This enzyme functions in the tricarboxylic acid (TCA) cycle and is also involved in ketone-body breakdown in animals. The enzyme is composed of alpha and beta subunits that are required for catalytic activity. Two genes, LSC1 (YOR142W) and LSC2 (YGR244C), with high similarity to succinyl-CoA ligase subunits from other species were isolated from Saccharomyces cerevisiae. The expression of these genes was repressed by growth on glucose and was induced threefold to sixfold during growth on nonfermentable carbon sources. The LSC genes were deleted singly and in combination. Unlike other yeast strains with defects in TCA cycle genes, strains lacking either or both LSC genes were able to grow with acetate as a carbon source. However, growth on glycerol or pyruvate was impaired. An antiserum against both subunits of the Escherichia coli enzyme was capable of recognizing the yeast succinyl-CoA ligase alpha subunit, and this band was absent in delta lsc1 deletion strains. Succinyl-CoA ligase activity was absent in mitochondria isolated from strains deleted for one or both LSC genes, but activity was restored by the presence of the appropriate LSC gene on a plasmid. The yeast succinyl-CoA ligase was shown to utilize ATP but not GTP for succinyl-CoA synthesis.

Acetates↗

PubMed1994

Evaluation of butorphanol and cyproheptadine for prevention of cisplatin-induced vomiting in dogs.

Cisplatin was administered at a dosage of 50 mg/m2 of body surface to 69 dogs with various neoplasms. Dogs were randomly assigned to receive antiemetics according to 1 of the following 5 protocols: group 1, no antiemetic (control, n = 45 treatments); group 2, 0.4 mg of butorphanol/kg of body weight (n = 52 treatments); group 3, 0.2 mg of butorphanol/kg (n = 19 treatments); group 4, 2 mg of cyproheptadine/kg (n = 48 treatments); and group 5, 1 mg of cyproheptadine/kg (n = 10 treatments). Randomization was performed for each dog prior to each treatment. Butorphanol was administered IM immediately after completion of cisplatin infusion. Cyproheptadine was given orally 12 to 14 hours before and again immediately before cisplatin administration. The proportion of dogs that vomited in group 1 was 40 of 45 (89%). Butorphanol at a dosage of 0.4 mg/kg proved highly effective in preventing cisplatin-induced vomiting, reducing the proportion of dogs that vomited (10/52, 19%) compared with the control group.

Animals↗

PubMed1994

Evaluation of mitoxantrone for the treatment of lymphoma in dogs.

Mitoxantrone was administered to 74 dogs with lymphoma at a dosage of 5.0 mg/m2 of body surface, IV, every 3 weeks. Thirty-four dogs had failed to respond to prior treatment with chemotherapeutic agents, which included doxorubicin (33 dogs). The remaining 40 dogs had not received prior treatment. Complete remission was determined in 19 of 74 dogs (26%), 10 of which had not received prior treatment. The median duration of remission for these 10 dogs was 94 days (range, 49 to 440 days, with 2 dogs still alive at 370 and 440 days, respectively). Nine dogs that had received prior treatment had complete remission that lasted for a median of 126 days (range, 42 to 792 days, with 1 dog still alive at 792 days). The combined remission rate (complete remission plus partial remission) was 41%. Toxicosis was minimal, developing in only 9 dogs and requiring hospitalization of 2 dogs. We concluded that the complete remission rate ascertained when mitoxantrone was the only treatment administered was low, compared with treatments that involved other chemotherapeutic agents; however, the combined remission rate of 41% indicated that mitoxantrone may be beneficial in the treatment of lymphoma in dogs.

Animals↗

PubMed1993

Longevity-determining genes in Caenorhabditis elegans: chromosomal mapping of multiple noninteractive loci.

We have used chromosome mapping with polymorphic markers to define genetic components governing life span in the nematode Caenorhabditis elegans. A complex recombinant-inbred population was derived from an interstrain cross, yielding > 1000 genotypes, each a composite of homozygous segments from the two parental strains. Genotypes were analyzed for the last-surviving 1-5% of worms in aging cohorts, and for young controls, by multiplex polymerase chain reaction using polymorphic markers to distinguish the parental alleles. We identified five regions of the genome at which one parental allele was significantly enriched in long-lived subpopulations. At four of five loci, the same alleles were selected in aging cohorts maintained under two different conditions, implying that these genes determine life span in differing environments.

Animals↗

PubMed1970