Database : HANSEN Search on : RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Subject descriptor] References found : 2 [refine] Displaying: 1 .. 2   in format [Detailed]

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Id: 17691 Author: Scollard, D. M; Adams, L. B; Gillis, T. P; Krahenbuhl, J. L; Truman, R. W; Williams, D. L Title: The continuing challenges of leprosy ..- Source: s.l; s.n; 2006. 44 p. ilus, tab. Abstract: Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases. (AU). Descriptors: Antiinfecciosos/TU Proteínas de Bactérias/ME Vacinas Bacterianas Modelos Animais de Doenças Suscetibilidade à Doença/IM Resistência Bacteriana a Drogas Genes Bacterianos/GE Predisposição Genética para Doença Genoma Bacteriano Imunidade Celular Imunidade Natural/GE Hansenostáticos/PD/TU Hanseníase/*/DI/MI/TH Mycobacterium leprae/*/CH/DE/IP/PH Nervos Periféricos/MI Doenças do Sistema Nervoso Periférico/MI/PA Reação em Cadeia da Polimerase Research Support, N.I.H., Extramural Células de Schwann/IM/MI Limits: HUMANO ANIMAL CAMUNDONGOS SUPPORT, NON-U.S. GOV'T Location: BR191.1; 09365/S

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Id: 17687 Author: Tapinos, Nikos; Ohnishi, Makoto; Rambukkana, Anura Title: ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli ..- Source: s.l; s.n; 2006. 6 p. ilus, tab, graf. Abstract: Demyelination is a common pathologic feature in many neurodegenerative diseases including infection with leprosy-causing Mycobacterium leprae. Because of the long incubation time and highly complex disease pathogenesis, the management of nerve damage in leprosy, as in other demyelinating diseases, is extremely difficult. Therefore, an important challenge in therapeutic interventions is to identify the molecular events that occur in the early phase before the progression of the disease. Here we provide evidence that M. leprae-induced demyelination is a result of direct bacterial ligation to and activation of ErbB2 receptor tyrosine kinase (RTK) signaling without ErbB2-ErbB3 heterodimerization, a previously unknown mechanism that bypasses the neuregulin-ErbB3-mediated ErbB2 phosphorylation. MEK-dependent Erk1 and Erk2 (hereafter referred to as Erk1/2) signaling is identified as a downstream target of M. leprae-induced ErbB2 activation that mediates demyelination. Herceptin (trastuzumab), a therapeutic humanized ErbB2-specific antibody, inhibits M. leprae binding to and activation of ErbB2 and Erk1/2 in human primary Schwann cells, and the blockade of ErbB2 activity by the small molecule dual ErbB1-ErbB2 kinase inhibitor PKI-166 (ref. 11) effectively abrogates M. leprae-induced myelin damage in in vitro and in vivo models. These results may have implications for the design of ErbB2 RTK-based therapies for both leprosy nerve damage and other demyelinating neurodegenerative diseases. (AU). Descriptors: Anticorpos Monoclonais/PD Butadienos/PD Células COS Células Cultivadas Cercopithecus aethiops Técnicas de Cocultura Doenças Desmielinizantes/*ME/PA Ativação Enzimática/DE Inibidores Enzimáticos/PD Células Hela Hanseníase/*ME/MI Camundongos Knockout Proteína Quinase 1 Ativada por Mitógeno/ME Proteína Quinase 3 Ativada por Mitógeno/ME Mycobacterium leprae/GE/*ME Nitrilos/PD Pirimidinas/PD Pirróis/PD Receptor erbB-2/*ME Research Support, N.I.H., Extramural Células de Schwann/EN/ME Nervo Ciático/ME/MI/UL Transdução de Sinal Limits: Ratos Camundongos Nus Camundongos Humanos Estudo Comparativo Animais Location: BR191.1; 09361/s

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