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R Blevins

Publications and source records attributed to R Blevins.

10 recordsLinked to original sources

Genome analysis with gene-indexing databases.

The recent release of the draft sequence and the eventual completion of the human genome present the scientific community with a rich source of data to mine. Yet, these data are content poor in the absence of additional correlative information. Expressed sequence tag (EST) datasets and their associated gene indices have existed for many years, and represent the first attempt at understanding the complexity of the genome. These datasets remain extremely important as information sources and, in particular, as tools for analyzing the completed genomes. Here, we discuss the nature of ESTs and their associated tools and gene-indexing databases. In particular, we will compare three EST gene indices (UNIGENE, Merck Gene Index Version 2.0 and Doubletwist CAT), discuss how these gene indices are applied for both genome analysis and drug discovery, and demonstrate their importance as a complementary dataset to the annotated human genome.

Databases, Factual↗

Storing biological sequence databases in relational form.

SUMMARY: We have created a set of applications using Perl and Java in combination with XML technology to install biological sequence databases into an Oracle RDBMS. An easy-to-use interface using Java has been created for database query and other tools developed to integrate with our in-house bioinformatics applications. AVAILIBILITY: The database schema, DTD file, and source codes are available from the authors via email. CONTACT: guochun_ xie@merck. com

Amino Acid Sequence↗

The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas.

A novel human Kir5.1 (inward rectifier K+ channel subunit, gene name KCNJ16) was identified through database searches. This human KCNJ16 was mapped to chromosome 17q25. The full-length cDNA was identified and its genomic structure was determined. Tissue distribution studies showed that human KCNJ16 is significantly expressed in human kidney, pancreas and thyroid gland. In situ hybridization revealed expression in convoluted tubule cells of kidney and in the acinar and ductal cells of pancreas. These suggest that human Kir5.1 may be involved in the regulation of fluid and pH balance, thus making it a potential therapeutic target for hypertension, renal failure, or pancreatic disease.

Amino Acid Sequence↗

Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial.

OBJECTIVES: The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to test the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS: The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6+/-1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS: In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16%; odds ratio, 1.43; 95% confidence interval, 0.71 to 2.89). CONCLUSIONS: Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Adenosine↗

PROFILER: a tool for automatic searching of internally maintained databases.

A new application program, the BIOINFORMATICS PROFILER, is described which simplifies the analysis of new genome sequence information appearing on a daily basis. Control tasks are defined through an intuitive graphical user interface and are executed at user defined nightly intervals. Electronic mail is sent to indicate that search results have been found. All task output is presented to users in the form of hypertext (HTML), allowing easy browsing. Currently supported tasks include BLAST and FastA sequence searching, keyword based searching of network news articles and WAIS databases, examination of GenBank sequence entries using regular expressions and boolean operations and protein sequence motif searching.

Amino Acid Sequence↗

The effect of coadministration of verapamil on the pharmacokinetics and metabolism of quinidine.

We have previously found that verapamil pretreatment significantly inhibits the metabolism of antipyrine. To assess more fully the implications of this observation, we examined the effect of verapamil on the pharmacokinetics and metabolism of quinidine. Pretreatment with verapamil, 80 mg and 120 mg (every 8 hours for 3 days), reduced the oral clearance of quinidine from 17.0 L/hr to 11.6 and 11.3 L/hr, respectively (P less than 0.01). The half-life of quinidine was also significantly prolonged by verapamil. The formation clearance of 3-hydroxyquinidine was reduced by 61.2% and 70.6% after verapamil pretreatment (80 and 120 mg, respectively) (P less than 0.01), whereas the renal clearance of unchanged quinidine was not affected. These results indicate that verapamil impairs the metabolism of quinidine to 3-hydroxyquinidine and reduces the oral clearance of quinidine to a degree that could be of clinical significance given the narrow therapeutic index of this drug.

Adult↗

The effect of verapamil on antipyrine pharmacokinetics and metabolism in man.

The effect of verapamil pre-treatment on the pharmacokinetics and metabolism of antipyrine was studied in eight healthy male volunteers. The oral clearance of antipyrine was decreased from 2.18 to 1.95 l h-1 (P less than 0.01) by verapamil (80 mg three times daily for 2 days prior to antipyrine administration and 2 days following) while half-life was increased from 13.2 to 15.6 h (P less than 0.01). The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 19.2%, 23.1% and 16.7% respectively (P less than 0.05) in the presence of verapamil. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 30%. These results suggest that verapamil is capable of inhibiting oxidative metabolism, a finding which could be of clinical significance for drugs highly dependent upon pathways such as those inhibited in this study for elimination.

Adult↗