Biomedical subjects

Helmy Rachman

Publications and source records attributed to Helmy Rachman.

4 recordsLinked to original sources

PubMed2006

Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.

Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-alpha as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products (AGE) during mycobacterial infection of macrophages, leading to apoptosis and activation of macrophages. Moreover, we demonstrate abundant AGE in pulmonary lesions of tuberculosis (TB) patients. Global gene expression profiling of MG-treated macrophages revealed a diverse spectrum of functions induced by MG, including apoptosis and immune response. Our results not only provide first evidence for the involvement of MG and AGE in TB, but also form a basis for novel intervention strategies against infectious diseases in which MG and AGE play critical roles.

Animals↗

PubMed2006

Reliable amplification method for bacterial RNA.

DNA microarray technology has been increasingly applied for studies of clinical samples. Frequently, RNA probes from clinical samples are available in limited amounts. We describe a reliable amplification method for bacterial RNA. We verified this method on mycobacterial RNA applying mycobacterial genome-directed primers (mtGDPs). Glass slide-based oligoarrays were employed to assess the quality of the amplification method. We observed a relatively small bias in amplified RNA pool when compared to the unamplified one. Up to 1000-fold linear RNA amplification in a single amplification round was obtained. To our knowledge, this study describes the first amplification method for mycobacterial RNA.

Moloney murine leukemia virus↗

PubMed2006

Mycobacterium tuberculosis gene expression profiling within the context of protein networks.

As one of the world's most successful intracellular pathogens, Mycobacterium tuberculosis, the causative agent of human tuberculosis, is responsible for two to three million deaths annually. The pathogenicity of M. tuberculosis relies on its ability to survive and persist within host macrophage cells during infection. It is of central importance, therefore, to identify genes and pathways that are involved in the survival and persistence of M. tuberculosis within these cells. Utilizing genome-wide DNA arrays we have identified M. tuberculosis genes that are specifically induced during macrophage infection. To better understand the cellular context of these differentially expressed genes, we have also combined our array analyses with computational methods of protein network identification. Our combined approach reveals certain signatures of M. tuberculosis residing within macrophage cells, including the induction of genes involved in DNA damage repair, fatty acid degradation, iron metabolism, and cell wall metabolism.

Amino Acids↗

PubMed2006

Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis.

Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identification of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal information from our DNA array analyses, we analyzed the differentially expressed genes within the context of computationally inferred protein networks. Protein networks were constructed using functional linkages established by the Rosetta stone, phylogenetic profile, conserved gene neighbor, and operon computational methods. This combined approach revealed that during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of genes involved in active fortification and evasion from host defense systems. These genes may provide targets for novel intervention strategies.

Bacterial Proteins↗