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Biomedical subjects

B Ewing

Publications and source records attributed to B Ewing.

9 recordsLinked to original sources
PubMed2001

Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex.

PURPOSE: To evaluate the effects of ganglion cell depletion from experimental glaucoma on the relative metabolic activities of neurons in the cytochrome oxidase blobs of V1 cortex in the macaque visual system. METHODS: Monocular experimental glaucoma was induced in adult monkeys (Macaca mulatta and Macaca fascicularis) by laser application to the trabecular meshwork, increasing the intraocular pressure. After other experiments, the primary visual cortices were analyzed for functional excitation from surviving ganglion cells, as indicated by cytochrome oxidase histochemistry. RESULTS: Cytochrome oxidase reactivity was uniformly reduced in blobs with input from the glaucomatous eye in a manner consistent with loss of known afferent inputs. The average size of glaucomatous blobs in layers 2 and 3 of V1 cortex was reduced by half. CONCLUSIONS: Experimental glaucoma in monkeys reduces retinal input to the central nervous system, thereby reducing the metabolic drive to downstream targets, as indicated by the reduction in the size of cytochrome oxidase blobs in layers 2 and 3 of V1 cortex. The pattern of cytochrome oxidase loss within the blob was uniform, suggesting that all sources of afferent input to the blobs were affected by experimental glaucoma.

Afferent Pathways↗
PubMed2000

Solid-phase combinatorial synthesis using MicroKan reactors, Rf tagging, and directed sorting.

A modular system for high-output solid-phase combinatorial synthesis has been designed and developed. The system employs three technological innovations to achieve its high efficiency and reliability: (1) application of microreactors as the reaction units in solid-phase synthesis; (2) use of radiofrequency tagging as the non-chemical tracking method; and (3) development of the directed sorting technology for split & pool synthesis. The system has been successfully applied in the synthesis of compound libraries of several hundred to several thousand compounds in multi-milligrams per compound quantity by many organizations.

Chemistry, Organic↗
PubMed2000

Analysis of expressed sequence tags indicates 35,000 human genes.

The number of protein-coding genes in an organism provides a useful first measure of its molecular complexity. Single-celled prokaryotes and eukaryotes typically have a few thousand genes; for example, Escherichia coli has 4,300 and Saccharomyces cerevisiae has 6,000. Evolution of multicellularity appears to have been accompanied by a several-fold increase in gene number, the invertebrates Caenorhabditis elegans and Drosophila melanogaster having 19,000 and 13,600 genes, respectively. Here we estimate the number of human genes by comparing a set of human expressed sequence tag (EST) contigs with human chromosome 22 and with a non-redundant set of mRNA sequences. The two comparisons give mutually consistent estimates of approximately 35,000 genes, substantially lower than most previous estimates. Evolution of the increased physiological complexity of vertebrates may therefore have depended more on the combinatorial diversification of regulatory networks or alternative splicing than on a substantial increase in gene number.

Alternative Splicing↗
PubMed1998

Base-calling of automated sequencer traces using phred. I. Accuracy assessment.

The availability of massive amounts of DNA sequence information has begun to revolutionize the practice of biology. As a result, current large-scale sequencing output, while impressive, is not adequate to keep pace with growing demand and, in particular, is far short of what will be required to obtain the 3-billion-base human genome sequence by the target date of 2005. To reach this goal, improved automation will be essential, and it is particularly important that human involvement in sequence data processing be significantly reduced or eliminated. Progress in this respect will require both improved accuracy of the data processing software and reliable accuracy measures to reduce the need for human involvement in error correction and make human review more efficient. Here, we describe one step toward that goal: a base-calling program for automated sequencer traces, phred, with improved accuracy. phred appears to be the first base-calling program to achieve a lower error rate than the ABI software, averaging 40%-50% fewer errors in the data sets examined independent of position in read, machine running conditions, or sequencing chemistry.

Algorithms↗
PubMed1998

Base-calling of automated sequencer traces using phred. II. Error probabilities.

Elimination of the data processing bottleneck in high-throughput sequencing will require both improved accuracy of data processing software and reliable measures of that accuracy. We have developed and implemented in our base-calling program phred the ability to estimate a probability of error for each base-call, as a function of certain parameters computed from the trace data. These error probabilities are shown here to be valid (correspond to actual error rates) and to have high power to discriminate correct base-calls from incorrect ones, for read data collected under several different chemistries and electrophoretic conditions. They play a critical role in our assembly program phrap and our finishing program consed.

Base Sequence↗
PubMed1997

Discovery and biological activity of orally active peptidyl trifluoromethyl ketone inhibitors of human neutrophil elastase.

Previously we had shown that tripeptidyl trifluoromethyl ketones (TFMKs) possessing an N-terminal diarylacylsulfonamide, such as ICI 200,880 and ICI 200,355, displayed unparalleled protection against the lung damage induced by human neutrophil elastase (HNE) when the inhibitors were administered intratracheally. Since the diarylacylsulfonamides were designed specifically to afford a long residence time in the lung, it was not unexpected that inhibitors from this class of TFMKs were not active when administered orally. Upon evaluating a large number of peptidyl TFMKs possessing a variety of N-terminal groups, several compounds were identified which demonstrated oral activity. Compounds were evaluated for their oral activity by measuring their ability to inhibit the increase in lung weight relative to body weight (Lw/Bw), the increase in red blood cells, and the increase in white blood cells induced by intratracheally administered HNE (100 micrograms/hamster). A number of tripeptidyl trifluoromethyl ketones containing neutral N-terminal groups displayed good oral activity, while those containing basic, acidic, or polar groups did not. Compound 50, possessing an N-terminal 4-(CH3O)C6H4CO group, was particularly effective, reducing Lw/Bw by 77%, red cells by 89%, and white cells by 91% when dosed at 37.5 mg/kg orally. Thus, by modifying the N-terminal group of tripeptidyl TFMKs, inhibitors can be designed which are effective in vivo when administered either orally or intratracheally.

Administration, Oral↗
PubMed1988

Management of illness and temporary disability in children enrolled in day-care centers. The Health House experience.

Alternative care arrangements are often necessary when children enrolled in day-care centers experience illness or temporary disability. To meet this need, a new facility named Health House was established by the Child Development Program of the Pomona (Calif) Unified School District. This report describes the organization, operation, and costs of the program, and reviews the management of 179 episodes of illness or temporary disability in 99 children served by the program during the 1983-1984 school year. The medical conditions of patients cared for were comparable with those seen in physicians' offices as reported in a national survey. The daily cost of care per child for the sponsoring agency was $38. The service enabled an average daily salary saving of $39.80 for the working parent. Health House may serve as a model for the management of illness or temporary disability in children enrolled in day-care centers.

Child Day Care Centers↗
PubMed1976

Western pine beetle: specificity among enantiomers of male and female components of an attractant pheromone.

The flight response of both sexes of Dendroctonus brevicomis to the mixture of myrcene, racemic frontalin, and (1R,5S,7R)-(+)-exo-brevicomin and to the mixture of myrcene, (1S,5R)-(-)-frontalin and racemic exo-brevicomin was significantly greater than the response to the same mixtures in which the antipodes were substituted. The flight response to these two mixtures was also greater than the response to the ternary mixture of myrcene, racemic frontalin, and racemic exo-brevicomin (MFE). The walking response of both sexes to the mixture of myrcene, racemic frontalin, and (+)-exo-brevicomin was not different from the response to MFE. Substitution of the antipode lowered the response when compared to that of MFE. When evaporated with ponderosa pine turpentine, (-)-frontalin was active in the field while its antipode was not.

Animals↗