15 research outputs found

    Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

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    Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Apoio ao Ensino Pesquisa e Assistencia do HC, Faculdade de Medicina de Ribeirao Preto, USPConselho Nacional de Desenvolvimento Cientifico e Tecnologic

    Variability of Pyricularia oryzae Cav. in irrigated rice genotypes

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    Rice blast, caused by the fungus Pyricularia oryzae Cav., is one of the most important diseases of rice. The understanding of its different strains allows a more efficient breeding towards resistant cultivars. This work aimed to determine the variability of the fungus and the prevalence of strains in irrigated rice genotypes, to evaluate the reaction of near isogenic lines of CO 39 to the collected P. oryzae isolates and to identify rice genotypes having complementary resistance genes to these isolates. The study was performed with 36 P. oryzae isolates collected in 18 irrigated rice cultivars from four counties in Rio Grande do Sul State, Brazil. A total of 21 strains were identified, with a prevalence for the IA group strains, in all collection sites, especially the IA-1 strain. A resistance reaction was observed for the cultivars BRS Firmeza, Bluebelle, Te-tep and BRS 7 (Taim), while a susceptible reaction was observed for Fanny, Dawn, BRS Pelota and BRS Atalanta. The series of near isogenic lines obtained from the CO 39 cultivar showed resistance to the isolates in the following order: C101 A51 (resistant to all isolates); C101 PKT (12); C104PKT (11); C105HP4L23 (8); and C101-LAC (3). From the studied isolates, it was concluded that there is variability of P. oryzae, prevalence of the IA strain, a higher tolerance for the cultivar BRS Firmeza and that the Pi-2 gene confers resistance to rice blast in all isolates analyzed
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