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Biomedical subjects

S D Brown

Publications and source records attributed to S D Brown.

At least 145 records · Page 8Linked to original sources

Comparative mapping on the mouse X chromosome defines a myotubular myopathy equivalent region.

The gene for X-linked myotubular myopathy (MTM1) has been localized to a 300-kb critical region in human Xq28 between IDS and GABRA3. As part of an effort to clone this gene, we developed a YAC contig on the mouse X Chromosome (Chr) which includes loci homologous to those within the human MTM1 critical region. The murine contig consists of 18 YACs and spans 2.5-3.0 Mb. We have aligned the human and murine physical maps by isolating conserved mouse genomic fragments, including CpG islands and trapped exons. We believe that the simultaneous isolation of genes from both mouse and human and continued comparative mapping will prove helpful in the eventual identification of MTM1 and other genes in the region.

Animals↗

Effect of stress and food variety on food intake in male and female rats.

Male and female rats were divided into two groups: stress (20 min of immobilization) and no stress. All animals were then given either one or three palatable foods for a 2 h test session. Each rat received both the single (one food) and variety (three foods) conditions twice, in a balanced order, in an ABAB experimental design. Stressed animals ate less than nonstressed animals. Animals ate more in the variety condition than in single condition during the first set of test sessions only. The stimulating effect of variety on food intake was not evident during the replication of conditions. All animals ate more of the palatable test foods than chow in a comparable time period. Rats ate more with each successive test session (regardless of food variety condition), showing a relative stabilization of food intake from the third to the fourth test sessions. However, there was a significant interaction of stress condition, sex, and test session. Stressed females continued to increase their food intake from the third to the fourth test session such that there was no longer any difference between the stressed and nonstressed females during the last test session. These results suggest that the effect of variety on food intake habituates when the same test foods are used repeatedly, and that there is no difference between males and females in the response to variety. Furthermore, while stress reduces the intake of palatable foods in all animals, females may show an habituation to this effect.

Animal Feed↗

Survey of antimicrobial activity of four commonly used third generation cephalosporins tested against recent bacterial isolates from ten American medical centers, and assessment of disk diffusion test performance. AST Surveillance Group.

Over 2,000 clinical isolates from ten American medical centers were tested for susceptibility to cefotaxine, ceftriaxone, ceftizoxime, and ceftazidime by both broth microdilution and disk diffusion methods. Typically resistant (e.g. enterococci) and highly susceptible (e.g. streptococci) isolates showed no change in susceptibility patterns compared to previous surveys. Pseudomonas aeruginosa and Stenotrophomonas maltophilia exhibited significant decreases in susceptibility to these cephalosporins. Among Escherichia coli and Klebsiella spp isolates, two to three percent were resistant to one of the four drugs whereas they were very susceptible to the other three. Of the four antibiotics, the cefotaxime disk diffusion test results correlated best with the microdilution results. With the other three drugs the disk diffusion test yielded 1 to 9% more susceptible test results and 1 to 20% fewer resistant test results than broth microdilution when testing gram negative bacilli. The clinical significance of such discrepancies is not known, but the impact on antibiotic susceptibility surveys and antibiogram comparisons could be significant.

Ceftazidime↗

Tentative interpretive criteria for testing the susceptibility of Streptococcus pneumoniae to eight fluoroquinolones.

Broth microdilution and disk diffusion methods were used to test ciprofloxacin, clinafloxacin, fleroxacin, grepafloxacin, ofloxacin, PD131628, sparfloxacin, and trovafloxacin against Streptococcus pneumoniae isolates. With each fluroquinolone tested, there was a striking unimodal population. With the exception of fleroxacin, over 96% of pneumococci tested were inhibited by each drug's modal MIC +/-1 twofold concentration. Over 92% of pneumococci produced inhibitory zone diameters equal to the mode +/-4 mm for each drug. For most fluoroquinolones, the interpretive criteria approved or proposed for nonfastidious organisms appear to be appropriate for pneumococci. For clinafloxacin and trovafloxacin, however, the proposed MIC breakpoints for nonfastidious organisms are four-to eightfold greater than the highest MIC encountered with pneumococci. For future surveillance efforts, low concentrations must be evaluated to detect any subtle shift in pneumococcal populations that might be undetected by testing only breakpoint concentrations.

Anti-Infective Agents↗

Does gastric tonometry work? Yes.

Gastric tonometry is gaining acceptance rapidly as a noninvasive method of monitoring tissue dysoxia in a key organ system that previously could not be assessed easily. In addition to being noninvasive, gastric tonometry also identifies dysoxia in shock sooner than currently available monitors. This allows for more timely intervention with a subsequent improvement in prognosis in defined groups of patients. Tonometry data that suggest continued dysoxia despite intervention should signal clinicians to seek alternative diagnoses or to question the efficacy of current therapies, including antibiotics.

Blood Gas Monitoring, Transcutaneous↗

Pulmonary lactate release in patients with sepsis and the adult respiratory distress syndrome.

PURPOSE: Elevated arterial lactate concentrations in patients with sepsis have been interpreted as evidence of peripheral, nonpulmonary tissue hypoxia. These patients often develop pulmonary failure manifested by the acute respiratory distress syndrome (ARDS). As the result of tissue hypoxia or inflammation, the lungs of patients with sepsis and ARDS may become a source of lactate release into the circulation. MATERIALS AND METHODS: Pulmonary lactate release was measured in 19 patients with sepsis, arterial lactate > or = 2.2 mm, and gastric mucosal pH > 7.30. A normal gastric mucosal pH served as a marker of adequate splanchnic oxygenation. Pulmonary lactate release was computed as the product of the cardiac index and the difference in plasma L-lactate concentration in simultaneously obtained arterial and mixed venous blood samples. Lung injury was graded with the Lung Injury Score using radiographic and physiologic data. RESULTS: The lungs of patients with minimal or no lung injury (lung injury score <1) produced significantly less lactate than those with moderate or severe lung injury (lung injury score > or = 1) (P < .005). The Lung Injury Score correlated with pulmonary lactate release (r2 = .73; P < .0001). This relationship resulted primarily from increases in mixed venous-arterial lactate differences (r2 = .59). The Lung Injury Score correlated weakly with the cardiac index (r2 = .32). Arterial lactate concentration did not correlate with pulmonary lactate release, systemic oxygen transport, or systemic oxygen consumption. CONCLUSIONS: The lungs of patients with sepsis and ARDS may produce lactate. Pulmonary lactate release correlates with the severity of lung injury. The contribution of pulmonary lactate release should be considered when interpreting arterial lactate concentration as an index of systemic hypoxia.

Acidosis, Lactic↗

Genetics of deafness.

The genetics of deafness is a rapidly expanding area of research. A remarkable total of twenty-two genes involved in non-syndromic deafness in humans have been localized within the past two years, compared with only one known previously. Some of the genes involved in neuroepithelial deafness, the most common type of pathology, have been identified in the past year. Two of these genes encode unconventional myosin molecules. The roles of these and other molecules identified by genetic approaches as important in hearing are being explored.

Animals↗

Isolation and characterization of a Drosophila gene essential for early embryonic development and formation of cortical cleavage furrows.

We have isolated a new female sterile mutant from Drosophila melanogaster, which arrests the embryonic development during the transition from syncytial to cellular blastoderm. Cytological analysis of the mutant embryos indicates that pseudocleavage furrows in the syncytial blastoderm are abnormal but not completely disrupted. However, cleavage furrows during cellularization are totally disorganized, and no embryos can develop beyond this stage. Consistent with this observation, the expression of this gene peaks around the cellular blastoderm and not in any later developmental stages. Based on immunofluorescence experiments, the protein product of this gene is localized in both pseudocleavage furrows at the syncytial blastoderm and in the cleavage furrows during the cellularization stage. Sequence homology analysis demonstrates a modest, but statistically significant, similarity of this protein with the carboxyl-terminal domains of dystrophin and a family of proteins collectively known as apodystrophins. It is possible that this protein may play an essential role in organizing and maintaining a specialized cytoskeletal structure, a function also suggested for dystrophin and apodystrophins.

Amino Acid Sequence↗

Xist expression from an Xist YAC transgene carried on the mouse Y chromosome.

We have constructed mouse transgenic lines carrying a YAC clone encompassing the Xist gene in order to investigate the factors influencing Xist expression and the initiation of X-inactivation. Two transgenic lines were derived, one carrying four copies integrated at an autosomal site and a second line carrying four copies integrated at a single site on the Y chromosome. Xist expression was not observed in mice carrying the autosomal insertion. However, Xist expression from the Y-inserted transgenes was observed and at levels commensurate with that found in normal female mice. Methylation sites in the autosomal transgene both 5' and 3' of the Xist gene are hypermethylated and appear to reflect methylation patterns observed on the active X chromosome. For the Y-linked transgene, methylation sites 5' and 3' of the Xist gene are hypomethylated reflecting patterns found on the inactive X chromosome. However, the 5' and 3' methylation levels have been decoupled at the active transgenic locus. The data suggest that sequences in the vicinity of Xist can initiate some of the features that are associated with the initiation process of X-inactivation.

Animals↗

In-vitro susceptibility of Streptococcus pneumoniae to the d- and l-isomers of ofloxacin: interpretive criteria and quality control limits.

The l-isomer of ofloxacin (levofloxacin) was twice as active as ofloxacin and the d-isomer was inactive against 654 Streptococcus pneumoniae isolates. For disc susceptibility tests of pneumococci, 5 micrograms levofloxacin discs can be used with interpretive criteria of < or = 12 mm for resistant (MIC > or = 8.0 mg/L) and > or = 16 mm for susceptible (MIC < or = 2.0 mg/L). For quality control of levofloxacin tests, S. pneumoniae ATCC 49619 should give zones 20-25 mm in diameter and MICs 0.5-2.0 mg/L.

Anti-Infective Agents↗

In vitro activities of five fluoroquinolone compounds against strains of Streptococcus pneumoniae with resistance to other antimicrobial agents.

Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.

Anti-Infective Agents↗

Prevalence of resistance to three fluoroquinolones: assessment of levofloxacin disk test error rates and surrogate predictors of levofloxacin susceptibility. AST Surveillance Group.

More than 3,000 consecutive clinical bacterial isolates from 10 U.S. medical centers were subjected to standard broth microdilution and disk diffusion tests to determine their susceptibilities to levofloxacin, ofloxacin, D-ofloxacin, and ciprofloxacin. Levofloxacin was confirmed to be twice as active as ofloxacin and to have activity comparable to that of ciprofloxacin, with minor variations in activity against some species. The prevalence of resistant isolates was 7.1% to levofloxacin, 9.3% to ciprofloxacin, and 11.2% to ofloxacin. The susceptibilities of some species to the quinolones were less than those reported in previous studies. Pseudomonas aeruginosa isolates had the greatest variability in their susceptibilities to the three drugs between the participating centers. Two proposed zone size breakpoints for levofloxacin disk tests yielded similar low error rates. Ofloxacin and ciprofloxacin susceptibility test results correlated reasonably well with those of levofloxacin and could be used as surrogate indicators of levofloxacin susceptibility, but that resulted in some serious errors, and thus, direct testing of levofloxacin susceptibility is preferable. Replicate testing of standard quality control strains confirmed the established and proposed quality control parameters for all three quinolones tested.

Anti-Infective Agents↗