HIRO GOTO

(Fonte: Lattes)
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Lattes
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Departamento de Medicina Preventiva, Faculdade de Medicina - Docente
LIM/38 - Laboratório de Epidemiologia e Imunobiologia, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 3 Citação(ões) na Scopus
    Staphylococcus aureus Protection-Related Type 3 Cell-Mediated Immune Response Elicited by Recombinant Proteins and GM-CSF DNA Vaccine
    (2021) SANTOS, Kamila R.; SOUZA, Fernando N.; RAMOS-SANCHEZ, Eduardo M.; BATISTA, Camila F.; REIS, Luiza C.; FOTORAN, Wesley F.; HEINEMANN, Marcos B.; GOTO, Hiro; GIDLUND, Magnus; CUNHA, Adriano F.; FARIA, Angelica Rosa; ANDRADE, Helida M.; LAGE, Andrey P.; CERQUEIRA, Monica M. O. P.; LIBERA, Alice M. M. P. Della
    Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit alpha (SAS), succinyldiaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations, and the intracellular interleukin-17A (IL-17A) and interferon-gamma production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A(+) cells among overall CD44(+) (memory), T CD4(+), CD4(+) T CD44(+) CD27(-), gamma delta TCR, gamma delta TCR+ CD44(+) CD27(+), and TCRV gamma 4(+) cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulated T(H)2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4(+), and CD4(+) TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.
  • article 8 Citação(ões) na Scopus
    Leptospirosis Infection in Sheep and Characterization of the Renal Inflammatory Response.
    (2011) CARVALHO, Sonia Maria de; GONCALVES, Larissa Maria Feitosa; MACEDO, Nicodemos Alves de; GOTO, Hiro; SILVA, Silvana Maria Medeiros de Sousa; MINEIRO, Ana Lys Bezerra Barradas; KANASHIRO, Edite Hatsumi Yamashiro; COSTA, Francisco Assis Lima
    Carvalho S.M., Gon alves L.M.F., Macedo N.A., Goto H., Silva S.M.M.S., Mineiro A.L.B.B., Kanashiro E.H.Y. & Costa F.A.L. 2011. [Leptospirosis Infection in Sheep and Characterization of the Renal Inflammatory Response.] Infeccao por leptospiras em ovinos e caracterizacao da resposta inflamatoria renal. Pesquisa Veterinaria Brasileira 31(8):637-642. Departamento de Clinica e Cirurgia Veterinaria, Centro de Ciencias Agrarias, Universidade Federal do Piaui, Campus Socopo, Teresina, PI 64046-550, Brazil. E-mail: fassisle@gmail.com Lepitospirosis is a serious worldwide distribution disease which affects man and other animals. The infection is generally asymptomatic in animals. In cases whose symptoms are present, symptoms are similar to other infections. In the present study serum samples from 119 sheep and their kidneys were collected during their slaughter in outdoor markets in the city of Teresina, Piaui, Brazil. The Microscopic Agglutination Test (MAT) obtained 34 positive serological samples for one or more Leptospira spp. serovar with occurrence rate of 28.6% of leptospiral antibodies. There were 23 cases of infection for a single serovar, and 11 cases with coagglutination for two or more serovars. Autumnalis had the highest occurrence (29.4%) among the pathogenic serovars. The histopathological analysis of 36 kidney fragments revealed tubulo-interstitial alterations in 33 (91.7%) positive animals. Tubular lesions were observed in 20 (55.5%) positive animals. The Warthin Starry staning revealed the presence of Leptospira in 8 (22.20%) of the 36 positive samples. The immunoperoxidase staining revealed the presence of Leptospira in 12 (60%) of 20 positive samples. The inflammatory infiltrate in the positive animals was significantly more evident in the cortical-medullar and cortical regions than in the medullar region (p=0.000), however, there was no difference between positive and negative animals. The presence of hyaline casts in the proximal tubules was significantly higher in positive animals compared to the negative ones (p=0.0001). Discrete lesion was observed in glomeruli. In conclusion, the results from this study showed that sheep which are positive for Leptospira present tubulo-intersticial renal lesions with the presence of Leptospira in the tubules, conferring to these animals the condition of asymptomatic carriers.
  • article 0 Citação(ões) na Scopus
    Recombinant protein KR95 as an alternative for serological diagnosis of human visceral leishmaniasis in the Americas
    (2023) FUJIMORI, Mahyumi; VALENCIA-PORTILLO, Ruth Tamara; LINDOSO, Jose Angelo Lauletta; CELESTE, Beatriz Julieta; ALMEIDA, Roque Pacheco de; COSTA, Carlos Henrique Nery; CRUZ, Alda Maria da; DRUZIAN, Angelita Fernandes; DUTHIE, Malcolm Scott; FORTALEZA, Carlos Magno Castelo Branco; OLIVEIRA, Ana Lucia Lyrio de; PANIAGO, Anamaria Mello C. Miranda; QUEIROZ, Igor Thiago; REED, Steve; VALLUR, Aarthy; GOTO, Hiro; SANCHEZ, Maria Carmen Arroyo
    In the Americas, visceral leishmaniasis (VL) is caused by the protozoan Leishmania infantum, leading to death if not promptly diagnosed and treated. In Brazil, the disease reaches all regions, and in 2020, 1,933 VL cases were reported with 9.5% lethality. Thus, an accurate diagnosis is essential to provide the appropriate treatment. Serological VL diagnosis is based mainly on immunochromatographic tests, but their performance may vary by location, and evaluation of diagnostic alternatives is necessary. In this study, we aimed to evaluate the performance of ELISA with the scantily studied recombinant antigens, K18 and KR95, comparing their performance with the already known rK28 and rK39. Sera from parasitologically confirmed symptomatic VL patients (n = 90) and healthy endemic controls (n = 90) were submitted to ELISA with rK18 and rKR95. Sensitivity (95% CI) was, respectively, 83.3% (74.2-89.7) and 95.6% (88.8-98.6), and specificity (95% CI) was 93.3% (85.9-97.2) and 97.8% (91.8-99.9). For validation of ELISA with the recombinant antigens, we included samples from 122 VL patients and 83 healthy controls collected in three regions in Brazil (Northeast, Southeast, and Midwest). When comparing the results obtained with the VL patients' samples, significantly lower sensitivity was obtained by rK18-ELISA (88.5%, 95% CI: 81.5-93.2) compared with rK28-ELISA (95.9%, 95% CI: 90.5-98.5), but the sensitivity was similar comparing rKR95-ELISA (95.1%, 95% CI: 89.5-98.0), rK28-ELISA (95.9%, 95% CI: 90.5-98.5), and rK39-ELISA (94.3%, 95% CI: 88.4-97.4). Analyzing the specificity, it was lowest with rK18-ELISA (62.7%, 95% CI: 51.9-72.3) with 83 healthy control samples. Conversely, higher and similar specificity was obtained by rKR95-ELISA (96.4%, 95% CI: 89.5-99.2), rK28-ELISA (95.2%, 95% CI: 87.9-98.5), and rK39-ELISA (95.2%, 95% CI: 87.9-98.5). There was no difference in sensitivity and specificity across localities. Cross-reactivity assessment, performed with sera of patients diagnosed with inflammatory disorders and other infectious diseases, was 34.2% with rK18-ELISA and 3.1% with rKR95-ELISA. Based on these data, we suggest using recombinant antigen KR95 in serological assays for VL diagnosis.
  • article 0 Citação(ões) na Scopus
    Staphylococcus aureus-Cure-Associated Antigens Elicit Type 3 Immune Memory T Cells
    (2022) SANTOS, Kamila R.; SOUZA, Fernando N.; RAMOS-SANCHEZ, Eduardo M.; BATISTA, Camila F.; REIS, Luiza C.; FOTORAN, Wesley L.; HEINEMANN, Marcos B.; CUNHA, Adriano F.; ROCHA, Mussya C.; FARIA, Angelica R.; ANDRADE, Helida M.; CERQUEIRA, Monica M. O. P.; GIDLUND, Magnus; GOTO, Hiro; LIBERA, Alice Maria M. P. Della
    Background: Staphylococcus aureus is one of the most frequently major mastitis pathogens that cause clinical and subclinical mastitis worldwide. Current antimicrobial treatments are usually ineffective, and the commercially available vaccines lack proven effectiveness. The immunological response elicited by the recombinant S. aureus-cure-associated proteins phosphoglycerate kinase (PGK), enolase (ENO), and elongation factor-G (EF-G) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA vaccination was studied in this work. Methods: Here, twenty-three C57BL/6 mice were divided into four groups and vaccinated with: G1: none (control); G2: GM-CSF DNA plasmid DNA vaccine; G3: the combination of EF-G+ENO+PGK; and G4: the combinations of EF-G+ENO+PGK proteins plus GM-CSF plasmid DNA vaccine. After 44 days, spleen cells were collected for immunophenotyping and lymphocyte proliferation evaluation by flow cytometry upon S. aureus stimulus. Results: Immunization with the three S. aureus recombinant proteins alone resulted in a higher percentage of IL-17A(+) cells among CD8(+) T central memory cells, as well as the highest intensity of IL-17A production by overall lymphocytes indicating that the contribution of the combined lymphocyte populations is crucial to sustaining a type 3 cell immunity environment. Conclusion: The immunization with three S. aureus-cure-associated recombinant proteins triggered type 3 immunity, which is a highly interesting path to pursue an effective bovine S. aureus mastitis vaccine.
  • article 4 Citação(ões) na Scopus
    Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy
    (2020) GONCALVES, Rafaela de Sousa; PINHO, Flaviane Alves de; DINIS-OLIVEIRA, Ricardo Jorge; AZEVEDO, Rui; GAIFEM, Joana; LARANGEIRA, Daniela Farias; RAMOS-SANCHEZ, Eduardo Milton; GOTO, Hiro; SILVESTRE, Ricardo; BARROUIN-MELO, Stella Maria
    Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient's prognosis.
  • article 1 Citação(ões) na Scopus
    Memory CD4+ and CD8+ T lymphocyte proliferation in vaccinated dairy cows with different histories of Staphylococcus aureus mastitis
    (2022) SOARES, Thais C. S.; SANTOS, Kamila R.; LIMA, Daniel M.; MAIA, Raysa Brenda M.; RAMOS-SANCHEZ, Eduardo M.; REIS, Luiza C.; GIDLUND, Magnus; CUNHA, Adriano F. da; ORDINOLA-RAMIREZ, Carla M.; CERQUEIRA, Monica M. O. P.; HEINEMANN, Marcos B.; LIBERA, Alice M. M. P. Della; GOTO, Hiro; SOUZA, Fernando N.
    Staphylococcus aureus mastitis constitutes a serious threat to dairy cows. The reasons why available vaccines are not fully effective remain poorly understood; thus, in the present study, we investigated CD4(+) and CD8(+) T lymphocyte proliferation in dairy cows vaccinated with a polyvalent mastitis vaccine that had distinct precedent Staphylococcus aureus mastitis. We studied 17 S. aureus-infected dairy cows (11 vaccinated and six unvaccinated) and eight vaccinated healthy dairy cows with no previous S. aureus mastitis infections. Flow cytometry was used to assess lymphocyte proliferation using an anti-Ki67 antibody, and monoclonal antibodies were used to identify T cell subsets. S. aureus-infected cows exhibited reduced overall lymphocyte proliferation, including CD4(+) T lymphocyte proliferation, and memory lymphocyte proliferation in response to S. aureus isolate stimulus. Immunization did not influence the expansion of blood lymphocyte populations. Furthermore, CD8(+) T cells, memory CD8(+) T lymphocytes, and effector memory CD8(+) T lymphocytes displayed reduced proliferation 21 days after the third vaccine dose compared with before vaccination at time zero. The present data demonstrates an overall negative regulation of the T-cell response suggesting its detrimental impact leading to the persistence of S. aureus intramammary infections. Furthermore, the lack of vaccination effect on T-cell mediated immunity (e.g., proliferation) may be related to poor vaccine efficacy.
  • article 14 Citação(ões) na Scopus
    Orange-Emitting ZnSe:Mn2+ Quantum Dots as Nanoprobes for Macrophages
    (2020) KHAN, Zahid U.; UCHIYAMA, Mayara K.; KHAN, Latif U.; RAMOS-SANCHEZ, Eduardo M.; REIS, Luiza Campos; NAKAMURA, Marcelo; GOTO, Hiro; SOUZA, Ana O. De; ARAKI, Koiti; BRITO, Hermi F.; GIDLUND, Magnus
    The biocompatibility, bionanointeraction, uptake efficiency, and entry pathway of luminescent nanomaterials are the key factors to understand development of an efficient bionanoprobe. The foremost objective of this work is to explore the potential of 3-mercaptopropionic acid (3-MPA) capped ZnSe:xMn(2+) (x = 5, 10, and 15 mol %) quantum dots (QDs) for the development of bionanoprobe used in future biological and clinical applications. For this purpose, highly intense orange-emitting activator Mn2+ ion doped ZnSe QDs were synthesized via a high-temperature organometallic method and rendered water-soluble by a ligand exchange approach. The morphological and physicochemical characterizations displayed the ultrasmall zinc-blend cubic crystal structure of QDs with an elliptical shape nanocrystals and average diameter of 4 nm. The luminescent nanomaterials exhibited orange emission centered at 584 nm under excitation at 385 nm. The biocompatibility, time-dependent cellular uptake, and the uptake mechanism of QDs were studied in RAW 264.7 macrophages, accomplished by various cytotoxicity assays, CytoViva hyperspectral enhanced dark-field and dual-mode fluorescence (DMF) microscopy, and transmission electron microscopy (TEM) images. The cytotoxicity study did not confirm any noticeable deleterious effect of QDs within incubation for 6 h. The fluorescence images of cells incubated with QDs showed efficient emission, which is a manifestation that QDs are photochemically stable in the intracellular environment. The cellular uptake findings demonstrated that the QDs were predominantly internalized via clathrin- and caveolae-mediated pathways. After the uptake, QDs aggregates appeared inside the vesicles in the cytoplasm, and their number and size gradually increased as a function of time. Nevertheless, the fluorescent QDs presented remarkable colloidal stability in various media, biocompatibility within the designated time, efficient time-dependent uptake, and distinct entry pathway in RAW macrophages, suggesting promising candidates to explore for the development of future bionanoprobes.