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Interferon research abs 1 || Hemoglobin research abs || Stem cell research abs || Nucleic acid research abs || Herpes research abs || Bronchitis research abs || Schizophrenia research abs || Tuberculosis research abs

J Public Health Manag Pract. 1995 Fall;1(4):52-4.
Tuberculosis, HIV disease, and directly observed therapy.

Brickner PW, McAdam JM.

Department of Community Medicine, St. Vincent's Hospital and Medical Center, New York, New York, USA.

Directly observed therapy (DOT) to enable completion of antituberculous therapy works. DOT is largely responsible for the recent improvement in tuberculosis case rates in New York City. Despite this favorable trend, the factors of significant HIV disease rates and of multidrug resistant forms of tuberculosis bacteria in the population are of grave concern. Therefore, in addition to DOT other means of preventing tuberculosis spread should be encouraged. These include directly observed preventive therapy (DOPT) programs, use of masks, improved ventilation in crowded settings such as homeless shelters, and ultraviolet light germicidal irradiation of upper room air in such locations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10186642&dopt=Abstract

Infect Immun. 2002 Jun;70(6):2926-32.
Identification by mass spectrometry of CD8(+)-T-cell Mycobacterium tuberculosis epitopes within the Rv0341 gene product.

Flyer DC, Ramakrishna V, Miller C, Myers H, McDaniel M, Root K, Flournoy C, Engelhard VH, Canaday DH, Marto JA, Ross MM, Hunt DF, Shabanowitz J, White FM.

Argonex, Inc., Charlottesville, Virginia 22903, USA.

Identification of Mycobacterium tuberculosis proteins that can provide immunological protection against tuberculosis is essential for the development of a more effective vaccine. To identify new vaccine targets, we have used immunoaffinity chromatography to isolate class I HLA-A*0201-peptide complexes from M. tuberculosis-infected cells and sequenced the isolated peptides by mass spectrometry. From this material, we have identified three peptides derived from a single M. tuberculosis protein that is encoded by the M. tuberculosis Rv0341 gene. Although no known protein encoded by the Rv0341 gene has been described, it is predicted to give rise to a 479-amino-acid protein with a molecular mass of 43.9 kDa. The three peptides identified are all nested and were found to be antigenic, in that they were capable of inducing peptide-specific, CD8(+) T cells from healthy blood donors in vitro and capable of recognizing and lysing M. tuberculosis-infected dendritic cells. This methodology provides a powerful tool for the identification of M. tuberculosis proteins that can be evaluated as potential vaccine candidates.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12010981&dopt=Abstract

Infect Immun. 2002 Jun;70(6):3020-5.
Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG.

Bouchonnet F, Boechat N, Bonay M, Hance AJ.

INSERM U552, Faculte de Medecine Xavier Bichat, Paris, France.

Administration of alpha/beta interferon (IFN-alpha/beta) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-alpha/beta has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-alpha/beta on mycobacterial growth in human monocytes/macrophages in vitro. Monocytes cultured at optimal cell density could control the growth of M. bovis BCG, as assessed both by measurement of luciferase activity expressed by a mycobacterial reporter strain and by counting of CFU. In contrast, unrestrained mycobacterial growth was observed when monocytes were treated with alpha interferon (IFN-alpha) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-alpha and IFN-beta and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-alpha modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-alpha on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-alpha/beta could directly promote mycobacterial growth in patients harboring these organisms.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12010993&dopt=Abstract

Infect Immun. 2002 Jun;70(6):3026-32.
Correlation of ESAT-6-specific gamma interferon production with pathology in cattle following Mycobacterium bovis BCG vaccination against experimental bovine tuberculosis.

Vordermeier HM, Chambers MA, Cockle PJ, Whelan AO, Simmons J, Hewinson RG.

Veterinary Laboratories Agency Weybridge, TB Research Group, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. mvordermeier.vltnet.gov.uk

Vaccine development and the understanding of the pathology of bovine tuberculosis in cattle would be greatly facilitated by the definition of immunological correlates of protection and/or pathology. To address these questions, cattle were vaccinated with Mycobacterium bovis bacillus Calmette-Guerin (BCG) and were then challenged with virulent M. bovis. Applying a semiquantitative pathology-scoring system, we were able to demonstrate that BCG vaccination imparted significant protection by reducing the disease severity on average by 75%. Analysis of cellular immune responses following M. bovis challenge demonstrated that proliferative T-cell and gamma interferon (IFN-gamma) responses towards the M. bovis-specific antigen ESAT-6, whose gene is absent from BCG, were generally low in vaccinated animals but were high in all nonvaccinated calves. Importantly, the amount of ESAT-6-specific IFN-gamma measured by enzyme-linked immunosorbent assay after M. bovis challenge, but not the frequency of responding cells, correlated positively with the degree of pathology found 18 weeks after infection. Diagnostic reagents based on antigens not present in BCG, like ESAT-6 and CFP-10, were still able to distinguish BCG-vaccinated, diseased animals from BCG-vaccinated animals without signs of disease. In summary, our results suggest that the determination of ESAT-6-specific IFN-gamma, while not a direct correlate of protection, constitutes nevertheless a useful prognostic immunological marker predicting both vaccine efficacy and disease severity.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12010994&dopt=Abstract

Infect Immun. 2002 Jun;70(6):3080-4.
Construction and phenotypic characterization of an auxotrophic mutant of Mycobacterium tuberculosis defective in L-arginine biosynthesis.

Gordhan BG, Smith DA, Alderton H, McAdam RA, Bancroft GJ, Mizrahi V.

MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, School of Pathology, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa.

A mutant of Mycobacterium tuberculosis defective in the metabolism of L-arginine was constructed by allelic exchange mutagenesis. The argF mutant strain required exogenous L-arginine for growth in vitro, and in the presence of 0.96 mM L-arginine, it achieved a growth rate and cell density in stationary phase comparable to those of the wild type. The mutant strain was also able to grow in the presence of high concentrations of argininosuccinate, but its auxotrophic phenotype could not be rescued by L-citrulline, suggesting that the DeltaargF::hyg mutation exerted a polar effect on the downstream argG gene but not on argH. The mutant strain displayed reduced virulence in immunodeficient SCID mice and was highly attenuated in immunocompetent DBA/2 mice, suggesting that L-arginine availability is restricted in vivo.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12011001&dopt=Abstract

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