Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy is an X-linked recessive disorder, primarily characterized by progressive muscle weakness and wasting. The disease results from the absence of dystrophin, however the precise molecular mechanisms leading to muscle pathology are poorly understood. Dystrophic muscles undergo increased oxidative stress and altered calcium homeostasis, which may contribute to myofiber loss by triggering both necrosis and apoptosis. Recent studies have identified ARC (apoptosis repressor with caspase recruitment domain) as an abundant protein in human muscle that can inhibit both hypoxia and caspase-8-induced apoptosis as well as protect cells from oxidative stress. To explore a potential role for ARC in protecting muscle fibers from dystrophic breakdown, we have cloned and characterized murine ARC and studied its expression in normal and dystrophic mouse muscle. ARC is expressed at high levels in striated muscle and displays fiber-type restricted expression patterns. ARC expression levels are normal in dystrophic mdx mice, although the intracellular localization pattern of ARC is slightly altered compared with normal muscles. Overexpression of ARC in transgenic mdx mice failed to alleviate the dystrophic pathology in skeletal muscles, suggesting that misregulation of the molecular pathways regulated by ARC does not significantly contribute to myofiber death.
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PMID:Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin-deficient skeletal muscle. 1464 4

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible "fatless" model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease.IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/reactivation.
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PMID:Adipose Tissue Regulates Pulmonary Pathology during TB Infection. 3099 60