Biomedical subjects
Publications and source records attributed to A J Mackey.
SUMMARY: A general system for performing multiple independent database searches in parallel is presented. Run-time addition and removal of clients, robust failure and error trapping and near 100% efficiency with very large numbers of clients are achieved by a flexible asynchronous, client-driven approach.
A protocol was developed for significantly reducing resident midgut bacteria in newly emerged anopheline mosquitoes using a combination of antibiotics. Pupa harvested from colony-reared Anopheles gambiae s.l. Giles and Anopheles stephensi (Liston) were placed in cages wiped previously with 70% alcohol and kept under UV light for 24 h. Emerging adult mosquitoes were fed for 3 consecutive days on antibiotic solution, consisting of 0.4% gentamicin sulfate and 1% penicillin-streptomycin solution in a 10% sterile sucrose solution. Bacterial suspensions of Escherichia coli, Klebsiella pneumoniae (Schroeter, 1886), and Pseudomonas stutzeri (Lehmann & Neumann, 1896) isolated from wild-caught anophelines were fed to antibiotic-treated mosquitoes starved for 24 h via either sugar or membrane-feeding. Mosquitoes dissected 1 and 24 h after blood-feeding or sugar-feeding, and plated on trypticase soy agar plates, yielded the same type of bacteria fed originally without evidence of contaminants. There was no residual effect of the antibiotics on introduced single bacteria strains as judged by the presence of bacteria in antibiotic-treated mosquitoes. This experimental reduction of resident midgut bacteria and their replacement with single strains in newly emerged anopheline mosquitoes should facilitate further investigations of the interactions between malaria parasites and bacteria found in the midguts of mosquitoes.
The membrane cytoskeletal component dystrophin and its associated glycoproteins play a central role in the molecular pathogenesis of several muscular dystrophies, i.e. Duchenne/Becker muscular dystrophy, congenital muscular dystrophy and various forms of limb-girdle muscular dystrophy. Although the most frequent of these disorders, Duchenne muscular dystrophy, is mainly recognized as a disease of skeletal muscle fibers, pathophysiological changes also involve the heart and diaphragm, as well as the peripheral and central nervous system. Thus current research efforts into the elucidation of the molecular mechanisms underlying these genetic diseases are not only directed towards studying skeletal muscle necrosis but also investigate abnormalities of heart and brain dystrophin-glycoprotein complexes in cardiomyopathy and brain deficiencies associated with muscular dystrophy. Furthermore, many isoforms of dystrophin and dystrophin-associated components have been identified in various non-muscle tissues and their function(s) are mostly unknown. With respect to skeletal muscle fibers, the characterization of new dystrophin-associated proteins, such as dystrobrevin, sarcospan and the syntrophins, led to a modified model of the spatial configuration of the dystrophin-glycoprotein complex. However, it is generally accepted now that beta-dystroglycan forms the plasmalemma-spanning linkage between dystrophin and the laminin-binding protein alpha-dystroglycan and that this complex is associated with the sarcoglycan subcomplex of sarcolemmal glycoproteins.
Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Th1 development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Th1/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.
The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naive T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.