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S D Brown

Publications and source records attributed to S D Brown.

At least 19 recordsLinked to original sources
PubMed2001

The XMaS beamline at ESRF: instrumental developments and high-resolution diffraction studies.

The beamline, which is situated on a bending magnet at ESRF, comprises a unique combination of instrumentation for high-resolution and magnetic single-crystal diffraction. White-beam operation is possible, as well as focused and unfocused monochromatic modes. In addition to an eleven-axis Huber diffractometer, which facilitates simple operation in both vertical and horizontal scattering geometries, there is an in-vacuum polarization analyser and slit system, mirrors for harmonic rejection, sub 4.2 K and 1 Tesla magnetic field sample environment, plus a diamond phase plate for polarization conditioning. The instrumentation developed specifically for this beamline is described, and its use illustrated by recent scientific results.

Journal Article↗
PubMed2001

Pincer-like amido complexes of platinum, palladium, and nickel.

The ligands bis(8-quinolinyl)amine (BQAH, 1), (2-pyridin-2-yl-ethyl)-(8-quinolinyl)amine (2-pyridin-2-yl-ethyl-QAH, 2), o-dimethylaminophenyl(8-quinolinyl)amine (o-(NMe2)Ph-QAH, 3), and 3,5-dimethylphenyl(8-quinolinyl)amine (3,5-Me2Ph-QAH, 4) have been prepared in high yield from aryl halide and amine precursors by palladium-catalyzed coupling reactions. Deprotonation of 1 with nBuLi in toluene affords the lithium amide complex [Li][BQA] (5), whose dimeric solid-state crystal structure is presented. Lithium amide 5 was transmetalated by TlOTf to afford the thallium(I) amido complex [Tl][BQA] (6). An X-ray structural study of 6 shows it to be a 1:1 complex of the BQA ligand and Tl. Entry into the group 10 chemistry of the parent ligand 1 was effected by both protolytic and metathetical strategies. Thus, the divalent chloride complexes (BQA)PtCl (7), (BQA)PdCl (8), and (BQA)NiCl (9) were prepared and fully characterized. An X-ray structural study for each of these three complexes shows them to be well-defined, square-planar complexes in which the auxiliary BQA ligand binds in a planar, eta(3)-fashion. For comparison, the reactivity of ligands 2-4 with (COD)PtCl2 was studied. While reaction with ligand 2 afforded an ill-defined product mixture, ligands 3 and 4 reacted with (COD)PtCl2 to generate the unusual alkyl complexes (o-(NMe2)Ph-QA)Pt(1,2-eta(2)-6-sigma-cycloocta-1,4-dienyl) (10) and (3,5-Me2Ph-QA)Pt(1,2-eta(2)-6-sigma-cycloocta-1,4-dienyl) (11), both of which have been structurally characterized.

Journal Article↗
PubMed2001

The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13.

Type 1 diabetes is a complex disorder with interaction of both genetic and environmental factors. One of the loci, IDDM4, has been mapped to chromosome 11q13, with evidence of association to two markers, D11S1917 and H0570polyA. To identify putative candidate genes for IDDM4, we have constructed a 400-kb clone contig in this region and sequenced the clones. We have also sequenced the orthologous DNA from mouse. Previously, we identified a cDNA for the low-density lipoprotein receptor-related protein 5 gene (LRP5) 3 kb distal to H0570polyA. We have now determined the exon-intron structure of this gene. Detailed sequence analysis has identified a further three genes in this region: the CGI-85 gene (previously identified by W.-C. Lin) and two novel genes, C11orf24 and C11orf23. The C11orf24 gene has no known similarity to other genes, and its function is unknown. C11orf23 has similarity to the SIT4 (sporulation-induced transcript 4)-associated protein (SAP) family of yeast proteins, which are involved in regulation of the cell cycle. The full-length C11orf23 cDNA is the first mammalian orthologue of the yeast SAP family to be identified. Identification of these four genes in a 400-kb region of the IDDM4 region underpins our strategy to identify the IDDM4 locus.

Amino Acid Sequence↗
PubMed2001

Myosin VIIA is specifically associated with calmodulin and microtubule-associated protein-2B (MAP-2B).

Myosin VIIA is a motor molecule with a conserved head domain and tail region unique to myosin VIIA, which probably defines its unique function in vivo. In an attempt to further characterize myosin VIIA function we set out to identify molecule(s) that specifically associate with it. We demonstrate that 17 and 55 kDa proteins from mouse kidney and cochlea co-purify with myosin VIIA on affinity columns carrying immobilized anti-myosin VIIA antibody. N-terminal sequencing and immunoblotting analysis identified the 17 kDa protein as calmodulin, whereas MS and immunoblotting analysis identified the 55 kDa protein as microtubule-associated protein-2B (MAP-2B). Myosin VIIA can also be co-immunoprecipitated from kidney homogenate using anti-calmodulin or anti-MAP2 (recognizing isoforms 2A and 2B) antibodies, confirming the strong association between calmodulin and myosin VIIA and between MAP-2B and myosin VIIA. Myosin VIIA binds to calmodulin with an apparent K(d) of 10(-9) M. Scatchard analysis of the binding of myosin VIIA to MAP-2B provided evidence for two binding sites, with K(d) values of 10(-10) and 10(-9) M, which have been mapped to medial and C-terminal tail domains of myosin VIIA. The characterization of the interaction of calmodulin and MAP-2B with myosin VIIA provides new insights into the function of myosin VIIA.

Amino Acid Sequence↗
PubMed2001

The mouse slalom mutant demonstrates a role for Jagged1 in neuroepithelial patterning in the organ of Corti.

The Notch signalling pathway has recently been implicated in the development and patterning of the sensory epithelium in the cochlea, the organ of Corti. As part of an ongoing large-scale mutagenesis programme to identify new deaf or vestibular mouse mutants, we have identified a novel mouse mutant, slalom, which shows abnormalities in the patterning of hair cells in the organ of Corti and missing ampullae, structures that house the sensory epithelia of the semicircular canals. We show that the slalom mutant carries a mutation in the Jagged1 gene, implicating a new ligand in the signalling processes that pattern the inner ear neuro-epithelium.

Animals↗
PubMed2001

The kyphoscoliosis (ky) mouse is deficient in hypertrophic responses and is caused by a mutation in a novel muscle-specific protein.

The ky mouse mutant exhibits a primary degenerative myopathy preceding chronic thoraco-lumbar kyphoscoliosis. The histopathology of the ky mutant suggests that Ky protein activity is crucial for normal muscle growth and function as well as the maturation and stabilization of the neuromuscular junction. Muscle hypertrophy in response to increasing demand is deficient in the ky mutant, whereas adaptive fibre type shifts take place. The ky locus has previously been localized to a small region of mouse chromosome 9 and we have now identified the gene and the mutation underlying the kyphoscoliotic mouse. The ky transcript encodes a novel protein that is detected only in skeletal muscle and heart. The identification of the ky gene will allow detailed analysis of the impact of primary myopathy on idiopathic scoliosis in mice and man.

Amino Acid Sequence↗
PubMed2001

Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse.

The Del(13)Svea36H deletion was recovered from a radiation mutagenesis experiment and represents a valuable resource for investigating gene content and function at this region of mouse Chromosome (Chr) 13 and human Chr 6p21.3-23 and 6p25. In this paper we examine the physical extent of chromosome loss and construct an integrated genetic and radiation hybrid map of the deleted segment. We show that embryos which are homozygous for the deletion die at or before implantation and that heterozygotes are subviable, with a substantial proportion of carriers dying after mid-gestation but before weaning. The majority of viable carriers exhibit a variety of phenotypes including decreased size, eyes open at birth, corneal opacity, tail kinks, and craniofacial abnormalities. Both the heterozygous viability and the penetrance of the visible phenotypes vary with genetic background.

Animals↗
PubMed2001

Relative potency of telithromycin, azithromycin and erythromycin against recent clinical isolates of gram-positive cocci.

A ketolide (telithromycin), an azalide (azithromycin) and a macrolide (erythromycin) were tested against 2,733 isolates of gram-positive cocci gathered from 11 different medical centers. Telithromycin was active against erythromycin-resistant staphylococci that were susceptible to clindamycin but was not active against those that were resistant to clindamycin. More than 99% of all Streptococcus pneumoniae and Streptococcus pyogenes isolates were susceptible to 1 microg/ml of telithromycin including erythromycin- and azithromycin-resistant strains. Telithromycin was not only more potent than azithromycin against macrolide-susceptible strains, it was also active against most macrolide-resistant strains. Although the prevalence of macrolide-resistant pneumococci increased from 19% to 27% between 1997 and 1999, macrolide resistance among other gram-positive cocci did not change substantially in that 2-year period.

Anti-Bacterial Agents↗
PubMed2001

Systematic approaches to mouse mutagenesis.

A major challenge in post-genomics is the systematic determination of mammalian gene function. A variety of mouse mutagenesis technologies, both gene- and phenotype-driven, are being used to underpin systematic and comprehensive approaches to mammalian gene function studies. Recently, a number of centres have completed large-scale ENU mutagenesis programmes that employ a phenotype-driven approach to the generation of mouse mutants. The use of ENU mutagenesis represents a powerful and efficient approach to mammalian gene-function studies, but many parallel developments are needed in downstream technologies to properly harness the new enlarged mouse-mutant resources that are being created.

Animals↗
PubMed2001

High-resolution quantitative trait locus mapping for body weight in mice by recombinant progeny testing.

A major obstacle to the positional cloning of quantitative trait loci (QTLs) lies in resolving genetic factors whose allelic effects are blurred by environmental and background genetic variation. We investigate a fine-mapping approach that combines the use of an interval-specific congenic strain with progeny testing of recombinants for markers flanking a QTL. We apply the approach to map a murine QTL with an approximately 20% effect on growth rate by progeny testing 39 recombinants in a 12 cM region of the X chromosome. We use a likelihood analysis in an attempt to maximize the information on QTL map location and effect. The major X-linked effect is mapped to an approximately 2 cM region flanked by markers about 5 cM apart, outside which LOD support for the QTL drops extremely steeply by about 80. Nearly unambiguous assignment of the QTL genotypic state is obtained for each recombinant. The resolution of individual recombinants in the region is therefore sufficiently high to facilitate the positional cloning of the locus, although progress has been hampered because the genomic region containing the QTL shows an exceptionally low level of polymorphism in comparison with recent studies.

Alleles↗
PubMed2001

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

Animals↗
PubMed2001

Interpretative criteria and quality control parameters for telithromycin disc diffusion susceptibility tests.

In vitro studies were carried out with 4175 Gram-positive clinical isolates, comparing telithromycin broth microdilution MICs with disc diffusion zone diameters. Provisional interpretive criteria for testing staphylococci were > or =23 mm for susceptible and < or =19 mm for resistant. Because pneumococci and other streptococci require increased CO(2), the corresponding zone sizes are 3 mm smaller (> or =20 mm and < or =16 mm). Two collaborative studies were performed in order to propose the following quality control limits: 24-30 mm for Staphylococcus aureus ATCC 25923 and 27-33 mm for Streptococcus pneumoniae ATCC 49619.

Anti-Bacterial Agents↗
PubMed2001

Comparative in vitro antimicrobial activity of a new carbapenem, E1010, and tentative disc diffusion test interpretative criteria.

The susceptibility of 705 bacterial isolates representing 46 different species to E1010 (ER-35786), imipenem, meropenem and cefepime was determined by the NCCLS broth microdilution test. The MIC(90)s for E1010 were < or =1.0 mg/L for Enterobacteriaceae, fastidious Gram-negative bacteria, streptococci and anaerobes. E1010 was two- to four-fold more active than imipenem and meropenem against Pseudomonas aeruginosa, and four-fold more active than the other carbapenems against methicillin-resistant Staphylococcus aureus. Vancomycin-resistant enterococci and most Enterococcus faecium were resistant to all four drugs tested. The NCCLS disc diffusion test was performed simultaneously on the non-fastidious organisms. Assuming the MIC breakpoints for E1010 will be the same as for the other carbapenems, the disc diffusion zone diameter breakpoints of imipenem and meropenem would also be applicable to E1010.

Anti-Bacterial Agents↗
PubMed2001

Evaluation of daptomycin susceptibility testing by Etest and the effect of different batches of media.

One hundred and ninety-five Gram-positive bacteria representing 17 species were tested for susceptibility to daptomycin by broth microdilution and Etest methods. The geometric mean daptomycin MIC was 0.46 mg/L by broth microdilution tests and 0.73 mg/L by Etest. The concentration of calcium in 12 different batches of agar varied from 4 to 36 mg/L. Daptomycin Etest MICs varied inversely with the calcium concentration. Etest daptomycin MICs for quality control strains were within proposed quality control range on media with >20 mg/L of calcium. Monitoring the calcium levels of agar media by testing appropriate quality control strains is important for daptomycin Etests.

Anti-Bacterial Agents↗
PubMed2001

In vitro activity of the ketolide ABT-773.

The in vitro activities of ABT-773, azithromycin, erythromycin, and clindamycin were compared by testing 1,223 clinical isolates selected to represent different species and phenotypes. ABT-773 was particularly potent against staphylococci (the MIC at which 90% of the strains tested were inhibited [MIC(90)] was < or =0.06 microg/ml), including all strains that were macrolide resistant but clindamycin susceptible. Streptococcus pneumoniae and other streptococci were inhibited by low concentrations of ABT-773, and that included most erythromycin-resistant strains. Against Haemophilus influenzae, ABT-773 and azithromycin were similar in their antibacterial potency (MIC(90), 4.0 and 2.0 microg/ml, respectively).

Drug Resistance, Bacterial↗
PubMed2001

Identification of beta-lactamase-negative, ampicillin-resistant strains of Haemophilus influenzae with four methods and eight media.

A challenge set of 143 non-beta-lactamase-producing strains of Haemophilus influenzae was tested for ampicillin susceptibility on two broth media and six agar media, using broth microdilution, agar dilution, disk diffusion, and E-test procedures. When beta-lactamase-negative, ampicillin-resistant (BLNAR) strains were defined as those for which the ampicillin MIC was > or = 4.0 microg/ml, 5 to 44% of our selected strains were BLNAR depending on the medium and/or test method used. If nonsusceptible strains for which ampicillin MICs were intermediate were included in the BLNAR category, 32 to 50% of our isolates would be considered BLNAR. These data emphasize the need for a standardized testing procedure and a universal definition of BLNAR strains before the clinical relevance of such strains can be evaluated. NCCLS dilution tests with haemophilus test medium broth or agar are preferred for testing ampicillin against H. influenzae.

Ampicillin↗