Advances in Cardiovascular Disease Lipid Research Can Provide Novel Insights Into Mycobacterial Pathogenesis

Cardiovascular disease (CVD) is the leading cause of death in industrialized nations and an emerging health problem in the developing world. Systemic inflammatory processes associated with alterations in lipid metabolism are a major contributing factor that mediates the development of CVDs, especially atherosclerosis. Therefore, the pathways promoting alterations in lipid metabolism and the interplay between varying cellular types, signaling agents, and effector molecules have been well-studied. Mycobacterial species are the causative agents of various infectious diseases in both humans and animals. Modulation of host lipid metabolism by mycobacteria plays a prominent role in its survival strategy within the host as well as in disease pathogenesis. However, there are still several knowledge gaps in the mechanistic understanding of how mycobacteria can alter host lipid metabolism. Considering the in-depth research available in the area of cardiovascular research, this review presents an overview of the parallel areas of research in host lipid-mediated immunological changes that might be extrapolated and explored to understand the underlying basis of mycobacterial pathogenesis

The Yeast Phase of Histoplasma Capsulatum Secretes: A Low Molecular Weight Calcium Binding Protein

iv, 34 p.Histoplasma capsulatum is a dimorphic fungus that is able to survive and grow within macrophages. It is the causative agent of histoplasmosis, one of the opportunistic infections associated with the Acquired Immune Deficiency Syndrome. Little is known about the mechanism of pathogenicity of this organism. Recently, it has been reported that phagosomes have a very low concentration of calcium (Pollack et al., 1986). Other organisms, such as Toxoplasma gondii, have adapted to life in this environment by secreting proteins which bind calcium. Does H. capsulatum use a similar adaptive strategy? To answer this question the calcium binding protein detection method developed by Maruyama et ale (1984) was utilized. The supernatant from cultures of H. capsulatum was concentrated by ultrafiltration to remove salts and other contaminants. After subjecting the proteins to either sodium dodecyl sulfate polyacrylamide gel electrophoresis or non-denaturing gel electrophoresis, a Western blot analysis was performed. A calcium binding protein with a molecular weight of about 6kd was apparent on the autoradiograph of the denaturing gel. This calcium binding protein was seen in ten different strains of H. capsulatum that correspond to four evolutionary classes. The protein appears to be highly conserved throughout these evolutionarily diverse strains and may be important in the virulence of the organism.Molecular Microbiology Department. Washington University. St. Louis, Missouri

IL-6 produced by macrophages infected with Mycobacterium species suppresses T cell responses.

Abstract The ability of Mycobacterium bovis Calmette-Guérin bacillus-infected bone marrow-derived macrophages to process and present exogenously added Ags to T cells and stimulate their growth and production of IL-2 was examined. The infected macrophages were inhibited in their ability to activate T cells, and this inhibition could be transferred to uninfected macrophages with filtered supernatants from mycobacteria-infected macrophages. The inhibition was not due to decreases in macrophage viability, Ag uptake, or cell surface expression of MHC class II or other accessory molecules necessary for Ag presentation. Other intracellular pathogens such as Listeria monocytogenes and Leishmania mexicana did not induce the soluble inhibitory factor, while Mycobacterium avium strain 101 did, suggesting the factor is specific to infection with mycobacteria. The inhibitory effect was reversed completely by preincubation with neutralizing Abs against IL-6, and rIL-6 partially restored the effect. Approximately 10,000-fold more IL-6 was produced by mycobacteria-infected macrophages compared with uninfected controls. Such sustained levels of IL-6 may account for the immune unresponsiveness apparent in both human and murine mycobacterial disease.</jats:p

Pic1: A Visual Database Interface Program

Many large image databases are springing up as cheap optical technology finally lets users store large numbers of images. The database community has few solutions to the problem of finding one image, picture, or face out of a million. We present a solution which is simple, intuitive, and permits image-based searching on a large database by selection. Keywords: interfaces, image databases, pictures, images, statistics, clustering, vector spaces, face recognition, image analysis, file identification, file indexing. 1 Introduction When designing interfaces for image databases, current database ideology suggests querybased interfaces expressed in SQL or similar languages (e.g. [4].) We believe this approach is not well suited to typical use. Query-based interfaces are hard for most non-experts to use, and wearying even for experts. Users must possess knowledge about the domain of the database, the functionality of the retrieval system, and the classification scheme employed by the databa..