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S D Brown

Publications and source records attributed to S D Brown.

At least 127 records · Page 7Linked to original sources
PubMed1997

Provisional interpretive criteria for quinupristin/dalfopristin susceptibility tests.

For testing bacterial susceptibility to the streptogramin quinupristin/dalfopristin, it seems reasonable that the test reagent should contain a similar ratio of the two compounds as in the therapeutic material, i.e. 30% quinupristin and 70% dalfopristin. The precise ratio of quinupristin to dalfopristin is not critical as long as threshold concentrations of both drugs are present. In-vitro tests were not altered by minor changes in pH, incubation in CO2 or by addition of lysed horse blood to the medium. Filter paper discs containing 15 micrograms of the quinupristin/dalfopristin reagent are preferred for agar diffusion susceptibility testing in order to optimize disc tests with enterococci. Provisional interpretive criteria for pathogens not requiring blood or increased CO2 are: susceptible, inhibition zone diameters of > or = 19 mm or MIC < or = 1.0 mg/L; intermediate, 16-18 mm or MIC 2.0 mg/L; resistant, < or = 15 mm or MIC > or = 4.0 mg/L. Those criteria will need to be reassessed as clinical experiences become available. Of particular concern is the role of quinupristin/dalfopristin in the treatment of infections due to Haemophilus influenzae or Enterococcus faecalis: the clinically relevant interpretive category for each of those two species is yet to be determined.

Anti-Bacterial Agents↗
PubMed1997

High-throughput microsatellite analysis using fluorescent dUTPs for high-resolution genetic mapping of the mouse genome.

The use of fluorescent end-labeled primers has proved successful for rapid, semiautomated genotyping of microsatellite loci. However, custom synthesis is expensive and costs can be prohibitive when a wide range of markers is to be analyzed for only a few genotypings. This particularly applies to high-resolution genetic mapping in the mouse either in the construction of global maps or in the production of local high-resolution genetic maps for positional cloning. We demonstrate here the use of fluorescent dUTPs for cost-effective, high-throughput microsatellite genotyping in the mouse. This alternative to the use of fluorescent end-labeled primers for semiautomated genotyping is potentially applicable to the construction of linkage maps in other species.

Animals↗
PubMed1997

Interpretive criteria and quality control parameters for testing of susceptibilities of Haemophilus influenzae and Streptococcus pneumoniae to trimethoprim and trimethoprim-sulfamethoxazole. The Antimicrobial Susceptibility Testing OC Group.

Two hundred twenty-eight strains of Haemophilus influenzae and 234 strains of Streptococcus pneumoniae were tested by broth microdilution and disk diffusion methods for susceptibility to trimethoprim (TMP) and TMP-sulfamethoxazole (SMX) to evaluate proposed criteria. Data are presented to support the proposed TMP MIC breakpoints of < or = 2.0 micrograms/ml for susceptibility and > or = 4.0 micrograms/ml for resistance for both species and TMP-SMX MIC breakpoints of < or = 2.0-38 micrograms/ml for susceptibility and > or = 4.0-76 micrograms/ml for resistance. Corresponding zone diameter breakpoints for H. influenzae for both drugs are proposed: < or = 10 mm = resistant; > or = 16 mm = susceptible. A 10-laboratory study documented reproducibility of such tests with standard control strains. The following control limits are proposed for tests of H. influenzae ATCC 49247 against TMP; MIC, 0.12 to 0.5 microgram/ml; zone diameter, 27 to 33 mm. The current limits for TMP-SMX were confirmed. For tests of S. pneumoniae ATCC 49619, MICs of TMP were 1.0 to 4.0 micrograms/ml and the current TMP-SMX MIC range was confirmed. Disk susceptibility tests of either drug against pneumococci were not reproducible, and consequently neither quality control limits nor interpretive criteria could be established. Endpoint interpretation and lot-to-lot variability in Mueller-Hinton agars were significant factors leading to interlaboratory variability.

Anti-Bacterial Agents↗
PubMed1997

Streptococcus pneumoniae killing rate and post-antibiotic effect of levofloxacin and ciprofloxacin.

In vitro killing rates for levofloxacin and ciprofloxacin for six strains of Streptococcus pneumoniae were determined by the time-kill method outlined by the NCCLS. Both drugs were bactericidal at concentrations of two and four times their respective minimum inhibitory concentrations (MICs). Levofloxacin achieved a 99.9% kill on average in 1 hour more rapidly than ciprofloxacin. Post-antibiotic effect was also determined for both drugs against the same six strains. A post-antibiotic effect for a mean of 1.2 and 1.0 hours was observed for levofloxacin and ciprofloxacin, respectively. The latter means were not considered significantly different.

Anti-Infective Agents↗
PubMed1997

Asbestos and silica-induced changes in human alveolar macrophage phenotype.

The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1+ phenotype (inducer or immune activator macrophages) and decreased the RFD1+ RFD7+ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation.

Apoptosis↗
PubMed1997

Hand in hand: social work leads students to volunteerism.

Healthy individuals, healthy families, and healthy relationships are crucial to a healthy society and are our most precious and valuable resources. Home care providers can play a role in developing and maintaining these resources.

Adult↗
PubMed1997

Unravelling the genetics of deafness.

Hearing-impaired mouse mutants not only are good models for human hereditary deafness, but also are extremely useful for understanding the molecular basis of the cochlear defect. We describe here how we identified the gene responsible for the deafness and vestibular defects in the shaker-1 mouse mutant as a myosin VII gene. Three different mutations, all causing the same phenotype in different lines of mouse, were found, providing good evidence that we had, indeed, found the correct gene. The same gene was subsequently found to be involved in Usher's syndrome type 1B, which features deafness, vestibular dysfunction, and progressive retinitis pigmentosa. The myosin VII gene is expressed in sensory hair cells, but not in supporting cells or neurons. We are investigating the role of myosin VII in hair cell development and function. Analysis of the different mutant stocks suggests it has at least two functions. First it is involved in the development and maintenance of the stereocilia bundle. Second, it has a role in inner hair cell function. No evidence of retinal degeneration like that in Usher's syndrome has been found in the shaker-1 mutants so far studied. The benefits of understanding the function of the gene for families with Usher's type 1B are discussed. This gene is the first to be identified as causing the most common type of disorder in human hearing impairment, neuroepithelial abnormalities, and suggests a new class of candidate genes for involvement in such defects.

Animals↗
PubMed1996

The Sp4H deletion may contain a new locus essential for postimplantation development.

Sp4H is a semi-dominant mutation that maps to mouse chromosome 1. Heterozygous mice exhibit white spotting of the belly, whereas the fate of the homozygous embryos is unknown. We have previously shown that the entire coding region of the Pax3 gene is deleted in the Sp4H mutant. In this study, we have analyzed the fate of the Sp4H homozygous embryos. No Sp4H homozygotes were detected by Southern blot or PCR analysis in 82 E9-E13-day embryos. We have also documented a significant increase in the number of resorption sites in Sp4H heterozygous matings compared to control litters. Sections of the resorption sites (moles) suggest that postimplantation development is arrested prior to gastrulation. We have mapped the extent of the deletion to a maximum of 1.53 +/- 0.6 cM using markers flanking the Pax3 locus. Four anonymous markers, D1Mit215, D1Mit253, D1Mit332, and D1McG156, have been shown to be deleted in the Sp4H mutation. Further nondeleted markers have been used to extend the linkage map of this region. A total of 22 loci were analyzed in a Splotch intraspecific backcross. Using these data and deletion mapping data, we predict the following order of markers: (D1Mit46, Vil)-(D1Mit79)-(D1Mit132, D1McG153)-(D1Mit332)-(D1-McG156, D1Mit253, D1Mit215, Pax3)-(D1Mit134)-(D1Mit8, D1Mit9, D1Mit44, D1Ler3, D1Mit183)-(D1Mit53, D1Mit82, D1Mit182)-(Bcl2). As the deletion is large enough to include other genes, and it seems that deletion of Pax3 is not likely to account for the early death of the embryos, we suggest that another developmentally important gene may be deleted in the Sp4H mouse mutant and that this may be responsible for the early death of the homozygous mutant embryos.

Alleles↗
PubMed1996

Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy.

The efficacy of ketamine (KET), a non-competitive NMDA receptor-channel blocker, was assessed in relieving nociceptive behaviors in neuropathic rats with tight ligations of the L5 and L6 spinal nerves. The antinociceptive effects of KET were dose- and time-dependent. A systemic injection of 0.01 mg/kg KET transiently (15-30 min) attenuated several nociceptive behaviors, including mechanical allodynia and hyperalgesia, cold allodynia, spontaneous pain, and cold stress-induced pain. Treatment with 1.0 mg/kg KET consistently decreased all nociceptive behaviors for 45-75 min, without noticeable side effects. Higher doses (25 and 50 mg/kg) provided longer lasting relief: however, these doses resulted in transient motor impairment which lasted for 15-30 min post-injection. Systemic KET was most effective in decreasing the behavioral signs of mechanical allodynia and hyperalgesia, followed by cold allodynia, cold stress-induced pain, and spontaneous pain. The present results demonstrate that blockade of NMDA receptors effectively alleviates nociceptive behaviors in a rat model of peripheral neuropathy, substantiating the important role of these receptors in the central sensitization that underlies the maintenance of neuropathic pain. In addition, the ability of KET to reduce significantly a variety of nocifensive behaviors suggests that this clinically safe drug could be used in pain management for neuropathic patients.

Animals↗
PubMed1996

In vitro activity and selection of disk content for disk diffusion susceptibility tests with trovafloxacin.

The activity of the new fluoroquinolone trovafloxacin (CP-99,219) was compared with that of ciprofloxacin and ofloxacin against 517 bacterial isolates representing 50 different species. Against members of the family Enterobacteriaceae, all three drugs showed good in vitro activity. Against most anaerobic bacteria, Staphylococcus, Streptococcus, and Enterococcus species, trovafloxacin was four- to sixteenfold more active than ciprofloxacin. For disk diffusion testing, 10 micrograms trovafloxacin disks gave satisfactory results. Tentative criteria are proposed for use during clinical studies.

Anti-Infective Agents↗
PubMed1996

In vitro activity of ceftizoxime, ceftazidime, cefuroxime, ceftriaxone, cefotaxime, and penicillin against Streptococcus pneumoniae as determined by three quantitative methods.

E-test, broth microdilution, and agar dilution susceptibility tests were used to evaluate penicillin and five extended-spectrum cephalosporins against 196 strains of Streptococcus pneumoniae with different levels of penicillin resistance. Oxacillin disk tests corresponded to minimum inhibitory concentrations of penicillin determined by the E-test better than those generated by broth microdilution or agar dilution methods. Relative potency of the study drugs was as follows: cefotaxime = ceftriaxone > penicillin > cefuroxime > ceftizoxime > ceftazidime.

Cefotaxime↗
PubMed1996

The cysteine-rich and C-terminal domains of dystrophin are not required for normal costameric localization in the mouse.

Dystrophin has a modular structure and is believed to be critical for muscle cell cytoarchitecture by linking the cytoskeleton to the extracellular matrix. The N-terminus binds to actin and two domains at the C-terminus, the cysteine-rich and C-terminal domains, are associated with the sarcolemma indirectly via the dystroglycan complex. We have generated a mutation in mouse embryonic stem (ES) cells which serves to delete the cysteine-rich and C-terminal domains to address directly their role. We show that these two domains are not necessary for normal costameric organization at the sarcolemma in myotubes derived from the mutant cell line. Furthermore sarcolemmal localization is also apparent in mouse chimaeric muscle in vivo.

Alleles↗
PubMed1996

YAC clone contigs covering 5 Mb of a repeat sequence island on the mouse X chromosome.

We have initiated work towards the construction of YAC clone contigs across a repeat sequence island region on the mouse X Chromosome (Chr). The repeat sequence island region-the 141 island-located at band A3 contains 50 copies of a localized long complex repeat unit (LCRU). We have isolated 87 YAC clones from the 141 island and have used a dual faceted approach towards the construction of contigs across the repeat sequence island. First, we have identified YAC clones originating from the same region of the island by the identification of commonly held LCRU restriction site variants. Second, we have constructed rare cutter restriction maps of each YAC clone. Taken together, we have been able to assemble one large contig of 2.8 Mb and a number of smaller contigs. In total, contigs covering 5Mb of the island region have been identified. The island region would appear to represent a major component of the A3 Giemsa dark band on the mouse X Chr.

Animals↗