Rosario Hirata

Publications (114) View all

• Article: Transcriptional responses of host peripheral blood cells to tuberculosis infection.

  Emil Lesho, Francisco J Forestiero, Mario H Hirata, Rosario D Hirata, Leticia Cecon, Fernando F Melo, Sun H Paik, Yoko Murata, Earl W Ferguson, Zhining Wang, Guck T Ooi
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  ABSTRACT: Host responses following exposure to Mycobacterium tuberculosis (TB) are complex and can significantly affect clinical outcome. These responses, which are largely mediated by complex immune mechanisms involving peripheral blood cells (PBCs) such as T-lymphocytes, NK cells and monocyte-derived macrophages, have not been fully characterized. We hypothesize that different clinical outcome following TB exposure will be uniquely reflected in host gene expression profiles, and expression profiling of PBCs can be used to discriminate between different TB infectious outcomes. In this study, microarray analysis was performed on PBCs from three TB groups (BCG-vaccinated, latent TB infection, and active TB infection) and a control healthy group. Supervised learning algorithms were used to identify signature genomic responses that differentiate among group samples. Gene Set Enrichment Analysis was used to determine sets of genes that were co-regulated. Multivariate permutation analysis (p < 0.01) gave 645 genes differentially expressed among the four groups, with both distinct and common patterns of gene expression observed for each group. A 127-probeset, representing 77 known genes, capable of accurately classifying samples into their respective groups was identified. In addition, 13 insulin-sensitive genes were found to be differentially regulated in all three TB infected groups, underscoring the functional association between insulin signaling pathway and TB infection.
  Tuberculosis (Edinburgh, Scotland) 08/2011; 91(5):390-9. · 2.54 Impact Factor
• Article: Rapid detection of resistance to pyrazinamide in Mycobacterium tuberculosis using the resazurin microtitre assay.

  Paula Aline Zanetti Campanerut, Luciana Dias Ghiraldi, Fernanda Luisa Espinoza Spositto, Daisy Nakamura Sato, Clarice Queico Fujimura Leite, Mário Hiroyuki Hirata, Rosário Dominguez Crespo Hirata, Rosilene Fressatti Cardoso
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  ABSTRACT: The resazurin microtitre plate assay (REMA) was evaluated to determine the susceptibility of Mycobacterium tuberculosis to pyrazinamide, and was compared with the broth microdilution method (BMM), the absolute concentration method (ACM) and pyrazinamidase (PZase) determination. Thirty-four M. tuberculosis clinical isolates (26 susceptible and 8 resistant to pyrazinamide) and reference strains M. tuberculosis H37Rv ATCC 27294 and Mycobacterium bovis AN5 were tested. REMA and BMM showed 100% specificity and sensitivity when compared with ACM; BMM, however, demanded more reading time. The PZase determination assay showed 87.50% and 100% sensitivity and specificity, respectively. All tested methods in this preliminary study showed excellent sensitivity and specificity for the determination of pyrazinamide susceptibility of M. tuberculosis, but REMA was faster, low-cost and easy to perform and interpret. Additional studies evaluating REMA for differentiating pyrazinamide-resistant and -susceptible M. tuberculosis should be conducted on an extended panel of clinical isolates.
  Journal of Antimicrobial Chemotherapy 03/2011; 66(5):1044-6. · 5.07 Impact Factor
• Article: Genotyping of Mycobacterium tuberculosis isolates from a low-endemic setting in northwestern state of Paraná in Southern Brazil.

  Erika Noda Noguti, Clarice Queico Fujimura Leite, Ana Carolina Malaspina, Adolfo Carlos Barreto Santos, Rosário Dominguez Crespo Hirata, Mario Hiroyuki Hirata, Elsa Massae Mamizuka, Rosilene Fressatti Cardoso
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  ABSTRACT: The purpose of this study was to provide information about the genetic diversity and prevalent genotype of Mycobacterium tuberculosis in a low-endemic setting in northwestern state of Paraná in Southern Brazil. We employed spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) techniques to genotype M. tuberculos isisolates from patients with pulmonary tuberculosis (TB). The 93 isolates analyzed by spoligotyping were divided into 36 different patterns, 30 of which were described in the SITVIT database. Latin American and Mediterranean, Haarlem and T families were responsible for 26.9%, 17.2% and 11.8% of TB cases, respectively. From the 84 isolates analyzed by MIRU-VNTR, 58 shared a unique pattern and the remaining 26 belonged to nine clusters. The MIRU loci 40, 23, 10 and 16 were the most discriminatory. A combination of MIRU-VNTR and spoligotyping resulted in 85.7% discriminatory power (Hunter-Gaston index = 0.995). Thus, combining spoligotyping and MIRU-VNTR typing proved to be most useful for epidemiological study in this low-endemic setting in Southern Brazil. The current study demonstrated that there is significant diversity in circulating strains in the city of Maringá and the surrounding regions, with no single genotype of M. tuberculosis predominating.
  Memórias do Instituto Oswaldo Cruz 09/2010; 105(6):779-85. · 2.15 Impact Factor
• Article: Uric acid biorhythm, a feature of long-term variation in a clinical laboratory database.

  Mauricio Pacheco de Andrade, Rosario D C Hirata, Fabiano Sandrini, Alvaro Largura, Mario Hiroyuki Hirata
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  ABSTRACT: The biorhythm of serum uric acid was evaluated in a large sample of a clinical laboratory database by spectral analysis and the influence of the gender and age on uric acid variability. Serum uric acid values were extracted from a large database of a clinical laboratory from May 2000 to August 2006. Outlier values were excluded from the analysis and the remaining data (n=73,925) were grouped by gender and age ranges. Rhythm components were obtained by the Lomb Scargle method and Cosinor analysis. Serum uric acid was higher in men than in women older than 13 years (p<0.05). Compared with 0-12 year group, uric acid increased in men but not in women older than 13 years (p<0.05). Circannual (12 months) and transyear (17 months) rhythm components were detected, but they were significant only in adult individuals (>26 years, p<0.05). Cosinor analysis showed that midline estimating statistic of rhythm (MESOR) values were higher in men (range: 353-368 μmol/L) than in women (range: 240-278 μmol/L; p<0.05), independent of the age and rhythm component. The extent of predictable change within a cycle, approximated by the double amplitude, represented up to 20% of the corresponding MESOR. Serum uric acid biorhythm is dependent on gender and age and it may have relevant influence on preanalytical variability of clinical laboratory results.
  Clinical Chemistry and Laboratory Medicine 01/2012; 50(5):853-9. · 2.15 Impact Factor
• Article: ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib.

  Douglas Vivona, Carolina T Bueno, Luciene T Lima, Rosario D C Hirata, Mario H Hirata, André D Luchessi, Maria A Zanichelli, Carlos S Chiattone, Elvira M Guerra-Shinohara
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  ABSTRACT: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML. One hundred eighteen CML patients initially treated with a standard dose of IM (400mg/day) for 18months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p=0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p=0.022). The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients.
  Blood Cells Molecules and Diseases 11/2011; 48(2):132-6. · 2.35 Impact Factor