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Biomedical subjects

D J Holmes

Publications and source records attributed to D J Holmes.

26 records · Page 2Linked to original sources

Cloning of aminoglycoside-resistance determinants from Streptomyces tenebrarius and comparison with related genes from other actinomycetes.

At least two aminoglycoside-resistance determinants from Streptomyces tenebrarius have been cloned separately in Streptomyces lividans. In each case, resistance (to kanamycin plus apramycin or to kanamycin plus gentamicin) was expressed at the level of the ribosome and involved specific methylation of 16S ribosomal RNA. Hybridization and restriction analysis revealed that related genes were present in other aminoglycoside-producing actinomycetes.

Actinomyces↗

Studies of the GTPase domain of archaebacterial ribosomes.

Ribosomes from the methanogens Methanococcus vannielii and Methanobacterium formicicum catalyse uncoupled hydrolysis of GTP in the presence of factor EF-2 from rat liver (but not factor EF-G from Escherichia coli). In this assay, and in poly(U)-dependent protein synthesis, they were sensitive to thiostrepton. In contrast, ribosomes from Sulfolobus solfataricus did not respond to factor EF-2 (or factor EF-G) but possessed endogenous GTPase activity, which was also sensitive to thiostrepton. Ribosomes from the methanogens did not support (p)ppGpp production, but did appear to possess the equivalent of protein L11, which in E. coli is normally required for guanosine polyphosphate synthesis. Protein L11 from E. coli bound well to 23S rRNA from all three archaebacteria (as did thiostrepton) and oligonucleotides protected by the protein were sequenced and compared with rRNA sequences from other sources.

Anti-Bacterial Agents↗

Detection of two distinct public specificities on HLA-A28 bearing lymphocytes.

We have used the antiglobulin augmented cytotoxicity assay and platelet absorption-elution techniques to investigate crossreactivity among certain antigens coded by the HLA-A locus. These serologic and absorption studies demonstrated two supertypic determinants, distinct from private determinants, associated with HLA-A locus gene products. One determinant was present on HLA-A2, Aw23, Aw24, and A28 bearing lymphocytes; the other was found on HLA-A28, Aw33, Aw34, and A26 bearing lymphocytes. The second determinant was not associated with HLA-A25. Both supertypic determinants are associated with HLA-A28.

Antibody Specificity↗

The detection of two serologically distinct HLA-A28 specificities.

We describe a serum, 9045, that detects a subset of A28 bearing cells in a mixed population of American blacks, Caucasians of Jewish ancestry and non-Jewish Caucasians. The serum reacts preferentially with A28 positive cells from American Blacks and Jewish Caucasians and does not react with non-Jewish Caucasians. This new specificity, referred to as A28.2, is strongly associated with HLA-B14. In contrast, A28 positive but 9045 negative cells (referred to as A28.1) do not show this association. The A28-2 determinants appears to be antigenically similar to the A28.1 determinant, but distinct from the public antigenic determinants shared by A28, A2, A9 and by A28, Aw33, Aw34 and A26. Based upon this analysis, we conclude that HLA-A28, as defined by most A28 antisera, comprises at least two populations of molecules. The A28.2 form may have arisen in the Mediterranean basin region, whereas the A28.1 form seems to be more prevalent in non-Jewish Caucasians of Northern European ancestry.

Absorption↗

Birds as long-lived animal models for the study of aging.

Despite their high lifetime energy expenditures, most birds can be characterized as long-lived homeotherms with moderately slow aging. A growing body of research confirms the prediction that birds have special adaptations for preventing aging-related oxidative and glycoxidative damage. Nonetheless, biogerontologists have been slow to develop avian laboratory models. A number of domestic poultry and cage bird species represent either established or very promising animal models for studies of basic aging processes and their prevention, including degenerative neurobiological, behavioral and reproductive processes. Several kinds of birds have also been used in studies of cellular resistance to oxidative stressors in vitro. Results of preliminary studies on chickens and quail suggest that caloric restriction may extend the reproductive life span of hens, but its long-term effects on life span remain unstudied. Birds' innate anti-aging mechanisms may actually make them more suitable in some respects as models of longevity than short-lived laboratory rodents, and bird studies may ultimately reveal routes for therapeutic intervention in diseases of human aging and infertility.

Aging↗