MARIA APARECIDA SHIKANAI YASUDA

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Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
LIM/48 - Laboratório de Imunologia, Hospital das Clínicas, Faculdade de Medicina

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  • article 17 Citação(ões) na Scopus
    Seroconversion of 2009 pandemic influenza A (H1N1) vaccination in kidney transplant patients and the influence of different risk factors
    (2013) AZEVEDO, L. S.; GERHARD, J.; MIRAGLIA, J. L.; PRECIOSO, A. R.; TIMENETSKY, M. dC S. Tavares; AGENA, F.; GAMBA, C.; YASUDA, M. A. Shikanai; DAVID-NETO, E.; PIERROTTI, L.
    BackgroundInfluenza may present a high morbidity and mortality in solid organ transplanted patients (SOTP). Annual influenza virus vaccine is recommended for SOTP. However, low levels of seroconversion in SOTP have been reported. The aim of this study was to evaluate the immunogenicity of 2009 pandemic influenza A (H1N1) - A(H1N1)pdm09 - vaccine in kidney transplant patients and to analyze which features might affect seroconversion. MethodsThis study was conducted from March to August 2010 at the Renal Transplantation Unit of University of SAo Paulo, Brazil. A total of 85 renal transplant patients attending the outpatient unit received one 15-g intramuscular dose of A(H1N1)pdm09 influenza vaccine (reassortant vaccine virus A/California/7/2009 [NYMC X-179A]). Blood samples were collected immediately before and 21days after the vaccine was given. Antibody response was measured by the standard hemagglutination-inhibition (HI) assay. The primary immunogenicity endpoint for this study was seroconversion in previously seronegative patients (HI titers <1:40), and the secondary endpoint was the identification of features that could affect seroconversion in this population. ResultsFive (5.9%) patients presented HI titers prevaccination 1:40 and were excluded from further analysis. Seroconversion in previously negative patients occurred in 27 (34%) of 80 patients. Prevaccination HI titers geometrical mean was 5.8 and postvaccination 19.6 (ratio 3.4). Significant seroconversion rate factors were female gender, non-Caucasian ethnicity, and post-transplant time before vaccination. No impact was seen on seroconversion for age, donor type, tacrolimus and cyclosporine blood levels, renal function, or blood lymphocyte counts. Mycophenolate (MPA) showed a lower rate of seroconversion when compared with azathioprine. Tacrolimus and cyclosporine had similar seroconversion rates. Sirolimus use was associated with the highest rate of seroconversion, although these patient numbers were low. Immunosuppresssion containing MPA was considerably less effective in seroconversion than drug combinations with no MPA. Patients receiving sirolimus had more chance of seroconversion. HI titers geometric means pre/post vaccine were as follows: MPA (n=56): 5.8/12.8; tacrolimus (n=50): 5.9/16.2; cyclosporine (n=18): 5.4/24.2; azathioprine (n=19): 6.2/51.6; and sirolimus (n=6): 8/80. By univariate analysis, being female and non-White were variables associated with 3.3 times more chance of seroconversion than being male and White. In the multivariate analysis, the variables remaining in the model showed similar hazard ratios. ConclusionsIn this study, the monovalent A(H1N1)pdm09 influenza vaccine demonstrated low rates of seroconversion, particularly in patients on MPA, but with potentially higher response rates in patients on sirolimus.
  • article 6 Citação(ões) na Scopus
    CURRENT TREATMENT OPTIONS FOR INVASIVE ASPERGILLOSIS
    (2013) BATISTA, M. V.; COSTA, S. F.; SHIKANAI-YASUDA, M. A.; MOSS, R. B.
    Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in immunocom promised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplant recipients. The optimal therapy for invasive aspergillosis relies on the restoration of leukocyte counts and effective antifungal treatment initiated at the earliest stage of infection. Several alternative antifungal compounds are currently available. A rational approach should take into account not only the degree of certainty of infection (as codified by the EORTC/MSG classification), but also previous exposure to other antifungals, the pharmacokinetic and pharmacodynamic characteristics of the antifungals employed and the clinical characteristics of the patient.
  • article 148 Citação(ões) na Scopus
    Paracoccidioidomycosis: eco-epidemiology, taxonomy and clinical and therapeutic issues
    (2013) BOCCA, Anamelia Lorenzetti; AMARAL, Andre Correa; TEIXEIRA, Marcus Melo; SATO, Paula; SHIKANAI-YASUDA, Maria Aparecida; FELIPE, Maria Sueli Soares
    Acquired by inhalation of the thermal dimorphic fungi Paracoccidioides spp. conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially fatal disseminated disease. The main focus of this review is to highlight clinical aspects of paracoccidioidomycosis and, its pathogens' diversity ecology and particularities. In addition, we present strategies for therapy, including DNA vaccines and nanostructured drugs. Molecular and morphological data supported the split of the Paracoccidioides genus into two species, Paracoccidioides brasiliensis and Paracoccidioides lutzii. An acute form of the disease affects approximately 5% of cases and involves the phagocytic mononuclear system, resulting in progressive lymphadenopathy. The chronic form affects adult men and frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal glands. The clinical manifestations depend on the ability of the host to control the fungal multiplication and dissemination. The long survival time of the fungus in the host tissues allows it to evade immune responses; therefore, successful treatment often requires long-time therapy. The consensus for treatment must consider the severity of the disease and includes sulfone derivatives, amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines and nanostructured drugs are also presented and discussed in this review.
  • conferenceObject
    CHAGAS DISEASE CARDIOMYOPATHY: ASSOCIATION WITH IL-17 AND IL-18 GENETIC POLYMORPHISMS
    (2018) SANTOS, Alexandra dos; FERREIRA, Daiane; OLIVEIRA, Jamile; OLIVEIRA, Claudia; BOCCHI, Edimar; NOVAES, Cristina; CRUZ, Fatima; CARVALHO, Noemia; SATO, Paula; FREITAS, Vera; SHIKANAI-YASUDA, Maria
  • article 16 Citação(ões) na Scopus
    Risk factor for death in hematopoietic stem cell transplantation: are biomarkers useful to foresee the prognosis in this population of patients?
    (2014) MASSARO, K. S. R.; MACEDO, R.; CASTRO, B. S. de; DULLEY, F.; OLIVEIRA, M. S.; YASUDA, M. A. S.; LEVIN, A. S.; COSTA, S. F.
    The morbidity and mortality in hematopoietic stem cell transplantation (HSCT) occur due to infectious complications and constitute the major clinical problems in HSCT recipients. The role of the use of biomarkers in post-HSCT patients is still controversial. To assess the serum values of biomarkers interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) and risk factors for post-HSCT death. Prospective study conducted in patients submitted to HSCT at a university hospital. Biomarkers (IL-6, PCT and CRP) were assessed on the day afebrile neutropenia was detected, in the febrile event, 24 and 72 h after fever onset and 48 h or 5 days if fever persisted. Patients were compared as to the death outcome within 30 days from the HSCT. Variables with p < 0.15 were included in the multivariate analysis model (MVA) that were performed for all patients included in the study and separated for autologous and allogeneic HSCT patients. 296 patients with ages ranging between 15 and 70 years, neutropenic, submitted to HSCT, being 216 (73 %) autologous and 80 (20 %) allogeneic were assessed. One hundred and ninety (64.2 %) patients presented fever after the transplantation and infection microbiologically controlled in 78 (26.4 %). Twenty-three cases (7.8 %) evolved to death. The risk factors associated with death in the bivariate analysis were age, allogeneic transplantation, unrelated transplantation, GVHD, bloodstream infection by Gram-negative, IL-6 > 140 pg/mL and CRP a parts per thousand yen120 mg/L and the protective ones were lymphoma and hospital outpatient support. The independent variables in the MVA associated with death were allogeneic and unrelated transplantation, blood stream infection (BSI) by Gram-negative, LDH a parts per thousand yen390 UI/L, urea a parts per thousand yen25 mg/dL and CRP a parts per thousand yen120 mg/L for HSCT transplanted patients and BSI due to Gram-negative and CRP a parts per thousand yen120 mg/L for allogeneic HSCT, however, CRP a parts per thousand yen120 mg/L did not remain in the model when urea a parts per thousand yen25 mg/L was included. No independent risk factor was found for autologous patients. Out of the biomarkers assessed, only CRP a parts per thousand yen120 mg/L was independently associated with death. Other risk factors found were: type of transplantation (allogeneic and unrelated), bloodstream infection by Gram-negative, LDH a parts per thousand yen390 UI/L and urea a parts per thousand yen25 mg/dL. For allogeneic patients only CRP a parts per thousand yen120 mg/L and BSI due to Gram-negative were risk factors for death; however, CRP did not remain in the model when urea a parts per thousand yen25 mg/L was included.
  • article 21 Citação(ões) na Scopus
    Multilocus Sequence Typing of Candida tropicalis Shows the Presence of Different Clonal Clusters and Fluconazole Susceptibility Profiles in Sequential Isolates from Candidemia Patients in Sao Paulo, Brazil
    (2013) MAGRI, Marcello Mihailenko Chaves; GOMES-GOUVEA, Michele Soares; FREITAS, Vera Lucia Teixeira de; MOTTA, Adriana Lopes; MORETTI, Maria Luiza; SHIKANAI-YASUDA, Maria Aparecida
    The profiles of 61 Candida tropicalis isolates from 43 patients (28 adults and 15 children) diagnosed with candidemia at two teaching hospitals in Sao Paulo, Brazil, were characterized by multilocus sequence typing (MLST). For the 14 patients who had bloodstream infections, 32 isolates were serially collected from their blood and/or catheters. Thirty-nine diploid sequence types (DSTs) were differentiated. According to the C. tropicalis MLST database (http://pubmlst.org/ctropicalis/), 36 DSTs and 23 genotypes identified from the 61 isolates had not previously been described. This report represents the first study to characterize sequential isolates of C. tropicalis from candidemia cases in South America. Microvariation in a single gene was found in the sequential isolates from 7 patients. The main polymorphisms occurred in the alleles of the XYR1 gene, specifically at nucleotide positions 215, 242, and 344. Macrovariation in six gene fragments was detected in the isolates from 3 patients. eBURST analysis added two new groups to this study (groups 6 and 18). Additionally, susceptibility tests indicate that 3 isolates were resistant to fluconazole. No correlation was found between the DSTs and susceptibility to fluconazole and/or selective antifungal pressure. Two patients were sequentially infected with resistant and susceptible strains. MLST is an important tool for studying the genetic diversity of multiple/sequential isolates of patients with candidemia, allowing the comparison of our data with those from other regions of the world, as well as allowing an analysis of the genetic relationship among several clones in sequential isolates from the same or different candidemia patient sites (blood or catheter).
  • article 13 Citação(ões) na Scopus
    Polymorphisms on IFNG, IL12B and IL12RB1 genes and paracoccidioidomycosis in the Brazilian population
    (2016) CARVALHO, F. M. C.; BUSSER, F. D.; FREITAS, V. L. T.; FURUCHO, C. R.; SADAHIRO, A.; KONO, A. S. G.; CRIADO, P. R.; MORETTI, M. L.; SATO, P. K.; SHIKANAI-YASUDA, M. A.
    Paracoccidioidomycosis (PCM) is a systemic chronic mycosis, endemic in Latin America, especially Brazil, and is the eighth leading cause of death among chronic and recurrent infectious diseases. PCM infection is characterized by the presence of Th1 immune response; the acute form, by a mixed Th2/Th9, while the chronic form is characterized by Th17/Th22 profiles. The occurrence and severity of human PCM may also be associated with genetic factors such as single nucleotide polymorphisms (SNP) on cytokines encoding genes. We investigated the association between these polymorphisms and the different clinical forms of PCM. We included 156 patients with PCM(40 with the acute form, 99 with the chronic multifocal and 17 with the chronic unifocal form) and assayed their DNA samples for IFNG + 874 T/A SNP by PCR-ARMS (Amplification Refractory Mutational System), IL12B + 1188 A/C SNP on 3' UTR and IL12RB1 641 A/G SNP on exon 7 by PCR-RFLP (Restriction Fragment Length Polymorphism). We found similar genotypic and allelic frequencies of the investigated SNPs among the clinical forms of PCM. Considering male patients, the IL12RB1 641 AA genotype was more frequent in the chronic multifocal form while heterozygosis was in the chronic unifocal form of PCM (p = 0.048). Although our data suggest that the AA genotype (IL12RB1) may be associated with the more disseminated chronic disease, more patients of the chronic unifocal PCM group need to be analyzed as well as the secretion patterns of IFN-gamma combined with the IL-12R beta 1 expression for a better comprehension of this association.
  • conferenceObject
    Interferon c and interleukin-12p40 genetic polymorphisms in brazilian patients with paracoccidioidomycosis
    (2012) HOLANDA, F. M. C.; SATO, P. K.; FREITAS, V. L. T.; YASUDA, M. A. Shikanai
    Paracoccidioidomycosis, caused by the thermal dimorphic fungus Paracoccidioides brasiliensis, is a chronic systemic granulomatous disease, endemic in South America, mainly in Brazil, being the eighth leading cause of death among infectious and parasitic diseases. Paracoccidioidomycosis infection is characterized by a Th1 response with secretion of IFN-c and basal levels of IL-10 and IL-4. In the acute form or juvenile a Th2 profile is predominant, with production of IL-10 and IL-4 and low levels of IFN-c. In chronic or adult, a mixed Th1 and Th2 profile is observed. The IFN-c can be induced by another cytokine, IL-12, and both are important in cellular immune response. In experimental models, IFN-c confers resistance to infection caused by Paracoccidioides brasiliensis and deficiency of IL-12p40 can cause susceptibility to this mycosis. The differential production of these cytokines may be associated with genetic polymorphisms. Objective: To investigate the association between the single nucleotide polymorphisms (SNP) IL-12B 3¢ UTR +1188 A/C and IFNG +874 T/A and the clinical forms of paracoccidioidomycosis. Materials and methods: DNA was obtained from peripheral blood samples from patients with paracoccidioidomycosis and healthy subjects. SNP IL-12B 3¢ UTR +1188 A/C was investigated with PCR-RFLP (PCR-Restriction Fragment Length Polymorphism) and SNP IFNG +874 T/A was investigated with PCR-ARMS (Polymerase Chain Reaction - Amplification Refractory Mutational System). Amplified products were visualized with electrophoresis on agarose gel. Results: In the SNP IFNG +874 T/A, the AA genotype was more frequent in the chronic multifocal and TA genotype in the unifocal. Considering the SNP IL-12B 3¢ UTR +1188 A/C there was a tendency for predominance of AC genotype in patients with chronic form, while the AA genotype was more frequent in acute. Despite this apparent difference among the groups, no statistically significant difference was observed in genotype distribution and alleles A, T and C. Conclusions: In this study there was no association between genetic polymorphisms of IL-12B 3¢ UTR +1188 A/C or IFNG +874 T/A and paracoccidioidomycosis, as well as with different clinical forms.
  • bookPart
    Doença de Chagas
    (2016) YASUDA, Maria Aparecida Shikanai; ZINGALES, Bianca
  • article 5 Citação(ões) na Scopus
    Characterization of Monocyte-Derived Dendritic Cells from Patients with Active and Treated Paracoccidioidomycosis
    (2011) SATO, P. K.; OSHIRO, T. M.; DIOGO, C. L.; PASSOS, E. C.; SHIKANAI-YASUDA, M. A.
    Cellular immune responses are a significant defence mechanism in human paracoccidioidomycosis (PCM), an endemic mycosis in Latin America; however, little is known about the role of dendritic cells (DCs) in human PCM. We investigated monocyte-derived DCs from patients with treated (TP) and active PCM (AP) compared with healthy non-PCM donors (CO). DCs from the TP group showed higher expression of HLA-DR, CD86 and DC-SIGN compared with CO, whereas AP showed similar expression to CO. Production of IL-10 was downregulated by TNF-a in all groups and lower levels were observed in untreated DCs from AP compared with CO. Conversely, IL-12p40 was significantly upregulated in the DCs of the TP group. TNF-a-activated DCs from the CO group produced significantly lower levels of IL-12p40 when differentiated from magnetic-sorted monocytes (MACS) compared with adhered monocyte-derived DCs. This comparison in the TP group revealed similar levels of IL-12p40, suggesting a T cellindependent increase in the production of IL-12p40. Higher expression of surface molecules with increased IL-12p40 may indicate a better activation of DCs after the treatment of PCM. Our findings suggest that DCs may be crucial in the protective response to Paracoccidioides brasiliensis and that in vitro-generated DCs might be useful in enhancing antifungal immunity, especially during active PCM.