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Biomedical subjects

Alan J A McBride

Publications and source records attributed to Alan J A McBride.

3 recordsLinked to original sources

High serum nitric oxide levels in patients with severe leptospirosis.

Leptospirosis is a globally distributed zoonosis of major public health importance and is associated with severe disease manifestations such as acute renal failure and pulmonary haemorrhage syndrome. However, the extent to which the pathogenesis of leptospirosis mimics sepsis caused by Gram-negative bacteria remains unknown. The aim of this study was to evaluate serum levels of nitric oxide (NO) in patients diagnosed with severe leptospirosis. Sera from 35 confirmed cases of severe leptospirosis and 13 healthy subjects were analysed. Patients with severe leptospirosis had significantly higher NO levels compared to healthy individuals (30.82+/-10.90 microM versus 3.86+/-1.34 microM, P < 0.001), indicating that this immune mediator plays a role in the underlying systemic inflammatory response.

Adolescent↗

Leptospirosis.

PURPOSE OF REVIEW: Leptospirosis, a spirochaetal zoonotic disease, has been recognized as an important emerging infectious disease in the last 10 years. This review addresses the issues in the epidemiology, diagnosis and clinical management which confront public health responses, and highlights the progress made towards understanding the Leptospira genome, biology and pathogenesis. RECENT FINDINGS: Leptospirosis has spread from its traditional rural base to become the cause of epidemics in poor urban slum communities in developing countries. Mortality from severe disease forms, Weil's disease and severe pulmonary haemorrhage syndrome, is high (>10% and >50%, respectively) even when optimal treatment is provided. Moreover, the overall disease burden is underestimated, since leptospirosis is a significant cause of undifferentiated fever and frequently not recognized. Barriers to addressing this problem have been the lack of an adequate diagnostic test and effective control measures. China and Brazil, countries in which leptospirosis is a major health problem, have completed the sequence of the Leptospira interrogans genome. Together with new genetic tools and proteomics, new insights have been made into the biology of Leptospira and the mechanisms used to adapt to host and external environments. Surface-exposed proteins and putative virulence determinants have been identified which may serve as sub-unit vaccine candidates. SUMMARY: Major progress has been made in the basic research of leptospirosis. Future challenges will be to translate these advances into public health measures for developing countries. Yet the most effective responses may be interventions that directly address the determinants of poverty, such as poor sanitation, which are often responsible for transmission.

Genome, Bacterial↗

Use of an arrayed promoter-probe library for the identification of macrophage-regulated genes in Mycobacterium tuberculosis.

The survival of Mycobacterium tuberculosis within the human host after infection, especially within macrophages, is likely to require the activation of a number of mycobacterial genes. To identify such genes, a promoter-probe library was constructed in which fragments of M. tuberculosis H37Rv DNA were inserted upstream of a lacZ reporter gene, using an Escherichia coli-mycobacterial shuttle vector. Mycobacterium bovis Bacille Calmette-Guérin (BCG) was subsequently transformed with this library and 4800 BCG clones were arrayed in a 96-well microtitre format, enabling the testing of individual clones for promoter activity under a variety of conditions. From preliminary screening, 41 clones were selected that exhibited upregulation of lacZ expression when subjected to acidified sodium nitrite. Subsequent sequence analyses identified 26 of these clones as containing potential promoters. After measuring lacZ expression in BCG clones recovered from a THP-1 macrophage cell line, three genes were selected for assessment of their expression in M. tuberculosis during macrophage infection, by real-time RT-PCR. Two of these genes, Rv1265 (with unknown function) and Rv2711 (encoding the iron-dependent repressor protein IdeR), showed evidence of being upregulated within macrophages.

Cell Line↗