YOUKO NUKUI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
14 resultados
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Agora exibindo 1 - 10 de 14
article 7 Citação(ões) na Scopus Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model(2023) ROSADAS, Carolina; SENNA, Katia; COSTA, Milene da; ASSONE, Tatiane; CASSEB, Jorge; NUKUI, Youko; COOK, Lucy; MARIANO, Livia; CASTRO, Bernardo Galvao; GRASSI, Maria Fernanda Rios; OLIVEIRA, Augusto Cesar Penalva de; CATERINO-DE-ARAUJO, Adele; MALIK, Bassit; BOA-SORTE, Ney; PEIXOTO, Paula; PUCCIONI-SOHLER, Marzia; SANTOS, Marisa; TAYLOR, Graham PhilipBackground Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107 center dot 74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide.bookPart Terapêutica Transfusional(2013) NUKUI, Youko- Immune Senescence-Related Gene Expression Profile in CD4+T-Lymphocytes of HTLV-1 Asymptomatic Carriers and Patients with Adult T-Cell Leukemia/Lymphoma (ATLL): A Brazilian Preliminary Study(2021) ASSIS FILHO, Jose Roberto; CULLER, Hebert Fabricio; LEVY, Debora; OLIVEIRA, Karolliny Silva de; NOGUEIRA, Daniel Silva; ALMEIDA, Lis Vilela de; ROCHA, Vanderson; NUKUI, Youko; LAGE, Luis Alberto de Padua Covas; PEREIRA, Juliana
- Molecular Characterization of Human T-Cell Lymphotropic Virus Type 1 Full and Partial Genomes by Illumina Massively Parallel Sequencing Technology(2014) PESSOA, Rodrigo; WATANABE, Jaqueline Tomoko; NUKUI, Youko; PEREIRA, Juliana; KASSEB, Jorge; OLIVEIRA, Augusto Cesar Penalva de; SEGURADO, Aluisio Cotrim; SANABANI, Sabri SaeedBackground: Here, we report on the partial and full-length genomic (FLG) variability of HTLV-1 sequences from 90 well-characterized subjects, including 48 HTLV-1 asymptomatic carriers (ACs), 35 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 7 adult T-cell leukemia/lymphoma (ATLL) patients, using an Illumina paired-end protocol. Methods: Blood samples were collected from 90 individuals, and DNA was extracted from the PBMCs to measure the proviral load and to amplify the HTLV-1 FLG from two overlapping fragments. The amplified PCR products were subjected to deep sequencing. The sequencing data were assembled, aligned, and mapped against the HTLV-1 genome with sufficient genetic resemblance and utilized for further phylogenetic analysis. Results: A high-throughput sequencing-by-synthesis instrument was used to obtain an average of 3210-and 5200-fold coverage of the partial (n = 14) and FLG (n = 76) data from the HTLV-1 strains, respectively. The results based on the phylogenetic trees of consensus sequences from partial and FLGs revealed that 86 (95.5%) individuals were infected with the transcontinental sub-subtypes of the cosmopolitan subtype (aA) and that 4 individuals (4.5%) were infected with the Japanese sub-subtypes (aB). A comparison of the nucleotide and amino acids of the FLG between the three clinical settings yielded no correlation between the sequenced genotype and clinical outcomes. The evolutionary relationships among the HTLV sequences were inferred from nucleotide sequence, and the results are consistent with the hypothesis that there were multiple introductions of the transcontinental subtype in Brazil. Conclusions: This study has increased the number of subtype aA full-length genomes from 8 to 81 and HTLV-1 aB from 2 to 5 sequences. The overall data confirmed that the cosmopolitan transcontinental sub-subtypes were the most prevalent in the Brazilian population. It is hoped that this valuable genomic data will add to our current understanding of the evolutionary history of this medically important virus.
- Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1-associated adult T-cell leukemia: a pilot study(2021) NASCIMENTO, Andrezza; SOUZA, Daniela Raguer Valadao de; PESSOA, Rodrigo; PIETROBON, Anna Julia; NUKUI, Youko; PEREIRA, Juliana; CASSEB, Jorge; OLIVEIRA, Augusto Cesar Penalva de; LOUREIRO, Paula; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri SaeedBackground Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(beta TGF-beta), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.
- Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study(2023) PESSOA, Rodrigo; SOUZA, Daniela Raguer Valadao de; NUKUI, Youko; PEREIRA, Juliana; FERNANDES, Lorena Abreu; MARCUSSO, Rosa Nascimento; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, Jorge; DUARTE, Alberto Jose da Silva; SANABANI, Sabri SaeedSmall RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.
- Frequency of human platelet antigens in oncohematological patients with thrombocytopenia and the probability of incompatibility to platelet transfusions(2012) BIANCHI, Juliana Vieira dos Santos; AZEVEDO, Maria Regina Andrade de; JENS, Eduardo; NUKUI, Youko; CHAMONE, Dalton Alencar FicherOBJECTIVE: The objective of this study was to evaluate the frequencies of human platelet antigens in oncohematological patients with thrombocytopenia and to analyze the probability of their incompatibility with platelet transfusions. METHODS: Platelet antigen genotyping was performed by sequence-specific primer polymerase chain reaction (SSP-PCR) for the HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b; HPA-15a, HPA-15b alleles in 150 patients of the Hematology Service of the Hospital das Clínicas (FMUSP). RESULTS: The allele frequencies found were: HPA-1a: 0.837; HPA-1b: 0.163; HPA-2a: 0.830; HPA-2b: 0.170; HPA-3a: 0.700; HPA-3b: 0.300; HPA-4a: 1; HPA-4b: 0; HPA-5a: 0.887; HPA-5b: 0.113; HPA-15a: 0.457 and HPA-15b: 0.543. CONCLUSIONS: Data from the present study showed that the A allele is more common in the population than the B allele, except for HPA-15. This suggests that patients homozygous for the B allele are more predisposed to present alloimmunization and refractoriness to platelet transfusions by immune causes. Platelet genotyping could be of great value in the diagnosis of alloimmune thrombocytopenia and to provide compatible platelet concentrates for these patients.
- Differential modulation of IL-4, IL-10, IL-17, and IFN-? production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and ?d) and B cells(2023) MACHADO, Nicolle Rakanidis; FAGUNDES, Beatriz Oliveira; FERNANDES, Lorena Abreu; OLIVEIRA, Augusto Cesar Penalva de; NUKUI, Youko; CASSEB, Jorge; CUNHA, Fernando Roberto Machado; NALI, Luiz Henrique da Silva; SANABANI, Sabri Saeed; VICTOR, Jefferson RussoHuman T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-?-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-?-producing ?dT cells without influence on IL-17- and IL4-producing ?dT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-? producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.
- Identification of miRnas with possible prognostic roles for HAM/TSP(2023) SOUZA, Daniela Raguer Valadao de; PESSOA, Rodrigo; NUKUI, Youko; PEREIRA, Juliana; MARCUSSO, Rosa Nascimento; OLIVEIRA, Augusto Cesar Penalva de; CASSEB, Jorge; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri SaeedHuman T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
- Small RNA profiles of HTLV-1 asymptomatic carriers with monoclonal and polyclonal rearrangement of the T-cell antigen receptor gamma-chain using massively parallel sequencing: A pilot study(2020) SOUZA, Daniela Raguer Valadao de; PESSOA, Rodrigo; NASCIMENTO, Andrezza; NUKUI, Youko; PEREIRA, Juliana; CASSEB, Jorge; OLIVEIRA, Augusto Cesar Penalva de; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri SaeedIn the present pilot study, massively parallel sequencing (MPS) technology was used to investigate cellular small RNA (sRNA) levels in the peripheral blood mononuclear cells (PBMCs) of human T-lymphotropic virus type I (HTLV-I) infected asymptomatic carriers with monoclonal (ASM) and polyclonal (ASP) T cell receptor (TCR) gamma gene. Blood samples from 15 HTLV-I asymptomatic carriers (seven ASM and eight ASP) were tested for the clonal TCR-gamma gene and submitted for sRNA library construction together with blood samples of five healthy controls (HCs) using Illumina sequencing platform. The sRNA-sequencing reads were aligned, annotated and profiled using various bioinformatics tools. Based on these results, possible markers were validated in the study samples by performing reverse transcription-quantitative (RT-q)PCR analysis. A total of 76 known sRNAs and 52 putative novel sRNAs were identified. Among them, 44 known and 34 potential novel sRNAs were differentially expressed in the ASM and ASP libraries compared with HCs. In addition, 10 known sRNAs were exclusively dysregulated in the ASM group and one (transfer RNA 65) was significantly upregulated in the ASP group.Homo sapiens(hsa) microRNA (miRNA/mir)-23a-3p, -28-5p, hsa-let-7e-5p and hsa-mir-28-3p and -361-5p were the most abundantly upregulated mature miRNAs and hsa-mir-363-3p, -532-5p, -106a-5p, -25-3p and -30e-5p were significantly downregulated miRNAs (P<0.05) with a >2-fold difference between the ASM and ASP groups compared with HCs. Based on these results, hsa-mir-23a-3p and -363-3p were selected for additional validation. However, the quantification of these two miRNAs using RT-qPCR did not provide any significant differences. While the present study failed to identify predictive sRNA markers to distinguish between ASM and ASP, the MPS results revealed differential sRNA expression profiles in the PBMCs of HTLV-1 asymptomatic carriers (ASM and ASP) compared with HCs.