2022/10/03 更新

写真a

トリイ ユカ
鳥居 ゆか
TORII Yuka
所属
医学部附属病院 小児科 助教
大学院担当
大学院医学系研究科
職名
助教
外部リンク

学位 1

  1. 博士(医学) ( 2014年3月   名古屋大学 ) 

研究キーワード 2

  1. 小児感染症

  2. 先天性サイトメガロウイルス感染症

現在の研究課題とSDGs 1

  1. ヘルペスウイルス科ウイルスにおける薬剤耐性の網羅的解析

経歴 2

  1. 名古屋大学医学部附属病院   小児科   医員

    2018年4月 - 2021年3月

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  2. 名古屋掖済会病院   小児科   医員

    2008年10月 - 2009年9月

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学歴 1

  1. 名古屋大学大学院   医学系研究科博士課程   小児科学

    2009年4月 - 2014年3月

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所属学協会 4

  1. 日本感染症学会

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  2. 日本小児感染症学会

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  3. 日本ワクチン学会

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  4. 日本ウイルス学会

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論文 40

  1. Next-Generation Sequencing to Detect Pathogens in Pediatric Febrile Neutropenia: A Single-Center Retrospective Study of 112 Cases

    Horiba Kazuhiro, Torii Yuka, Okumura Toshihiko, Takeuchi Suguru, Suzuki Takako, Kawada Jun-Ichi, Muramatsu Hideki, Takahashi Yoshiyuki, Ogi Tomoo, Ito Yoshinori

    OPEN FORUM INFECTIOUS DISEASES   8 巻 ( 11 ) 頁: ofab223   2021年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/ofid/ofab223

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  2. A Case of Descending Necrotizing Mediastinitis in a Previously Healthy Child

    Okumura Toshihiko, Tetsuka Nobuyuki, Yamaguchi Makoto, Suzuki Takako, Torii Yuka, Kawada Jun-ichi, Ito Yoshinori

    CASE REPORTS IN PEDIATRICS   2021 巻   頁: 3159092   2021年9月

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    記述言語:日本語  

    DOI: 10.1155/2021/3159092

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  3. Pediatric sepsis cases diagnosed with group B streptococcal meningitis using next-generation sequencing: a report of two cases 国際誌

    Horiba Kazuhiro, Suzuki Michio, Tetsuka Nobuyuki, Kawano Yoshihiko, Yamaguchi Makoto, Okumura Toshihiko, Suzuki Takako, Torii Yuka, Kawada Jun-ichi, Morita Makoto, Hara Shinya, Ogi Tomoo, Ito Yoshinori

    BMC INFECTIOUS DISEASES   21 巻 ( 1 ) 頁: 531 - 531   2021年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Infectious Diseases  

    Background: Group B Streptococcus (GBS) is an important cause of invasive infection in neonates and infants. Cerebrospinal fluid (CSF) findings and culture may not show evidence of infection early in GBS meningitis. Next-generation sequencing (NGS) has the potential to detect microbial genetic material in patients with infectious diseases. We report two cases of infantile sepsis of GBS meningitis with negative results for CSF culture tests, but positive results for NGS analysis. Case presentation: Patient 1 was a 22-day-old male infant diagnosed with sepsis and meningitis. His CSF findings showed pleocytosis, decreased glucose, and increased protein levels. However, CSF and blood culture results at admission were negative. He received a total of 3 weeks of treatment with ampicillin and cefotaxime, and showed clinical improvement. GBS was detected through NGS analysis of CSF collected at admission. Patient 2 was a 51-day-old male infant with sepsis. CSF findings on admission were normal, and blood and CSF cultures were also negative. Intravenous ampicillin and cefotaxime treatment were initiated. Treatment was de-escalated to ampicillin alone because Enterococcus faecalis was cultured from urine. He was discharged after a total of 1 week of antibiotic treatment. Six days after discharge, he was re-hospitalized for sepsis. Blood and CSF cultures were negative, and E. faecalis was again cultured from urine. He received a total of 3 weeks of ampicillin treatment for enterococcal-induced nephritis and did not relapse thereafter. NGS pathogen searches were retrospectively performed on both blood and CSF collected at the first and second admission. GBS was detected in the CSF collected at the first admission, but no significant pathogen was detected in the other samples. Inadequate treatment for GBS meningitis at the first admission may have caused the recurrence of the disease. Conclusion: Infantile sepsis may present bacterial meningitis that is not diagnosed by either culture testing or CSF findings. NGS analysis for CSF may be useful for confirming the diagnosis of bacterial meningitis.

    DOI: 10.1186/s12879-021-06231-3

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  4. MRI findings in children with congenital cytomegalovirus infection retrospectively diagnosed with dried umbilical cord 国際誌

    Kidokoro Hiroyuki, Shiraki Anna, Torii Yuka, Tanaka Masaharu, Yamamoto Hiroyuki, Kurahashi Hirokazu, Maruyama Koichi, Okumura Akihisa, Natsume Jun, Ito Yoshinori

    NEURORADIOLOGY   63 巻 ( 5 ) 頁: 761 - 768   2021年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Neuroradiology  

    Purpose: Brain MRI provides important information about suspected congenital CMV infection in neonatally underdiagnosed children. This study aimed to describe MRI findings in children in whom congenital CMV infection was not suspected during the neonatal period and was proven retrospectively. Methods: We enrolled 31 children referred to the pediatric neurology clinic with neurological symptoms who were proven to have congenital CMV infection based on dried umbilical cord samples. Upon diagnosis, MR and CT images were assessed using the van der Knaap scoring system integrated with additional variables. Two investigators independently assessed all images. Results: The age at diagnosis was < 12 months in 14, 12–24 months in 11, and > 24 months in 6 patients. The initial symptom triggering clinic referral was delayed development in 22, seizure in 5, deafness in 3, and hemiplegia in 1 patient. Of the 31 children, 30 had a white matter (WM) abnormality predominant in the deep WM of the parietal lobe (n = 25). Anterior temporal lesions were observed in 21 children. Cortical lesions were observed in 7 children, suggestive of polymicrogyria. No child had cerebellar or brainstem abnormalities. Brain CT was performed in 22 of 31 children, and 11 showed punctate cerebral calcification in the periventricular and/or deep WM. Conclusion: Patients with congenital CMV infection with delayed neurological symptoms show a relatively uniform pattern of parietal-dominant multifocal WM lesions and anterior temporal lesions, with or without polymicrogyria.

    DOI: 10.1007/s00234-020-02603-9

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  5. Temporal dynamics of the plasma microbiome in recipients at early post-liver transplantation: a retrospective study

    Okumura Toshihiko, Horiba Kazuhiro, Kamei Hideya, Takeuchi Suguru, Suzuki Takako, Torii Yuka, Kawada Jun-ichi, Takahashi Yoshiyuki, Ogura Yasuhiro, Ogi Tomoo, Ito Yoshinori

    BMC MICROBIOLOGY   21 巻 ( 1 ) 頁: 104   2021年4月

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    記述言語:日本語   出版者・発行元:BMC Microbiology  

    Background: Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection but poses a risk for severe infectious diseases. Immune modulation and antimicrobials affect the plasma microbiome. Thus, determining the impact of immunosuppression on the microbiome may be important to understand immunocompetence, elucidate the source of infection, and predict the risk of infection in LT recipients. We characterized the plasma microbiome of LT recipients at early post-LT and assessed the association between the microbiome and clinical events. Results: In this study, 51 patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected at the following time points: 1) within a week after LT; 2) 4 ± 1 weeks after LT; 3) 8 ± 1 weeks after LT; and 4) within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS) with the PATHDET pipeline. Relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period. Microbiome diversity was higher within a week after LT than that at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly increased and the plasma microbiome diversity was significantly lower in patients with acute cellular rejection (ACR) than non-ACR patients. Sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples, and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe clinical condition. Conclusions: The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients.

    DOI: 10.1186/s12866-021-02154-w

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  6. Immune cell infiltration landscapes in pediatric acute myocarditis analyzed by CIBERSORT

    Kawada Jun-ichi, Takeuchi Suguru, Imai Hiroshi, Okumura Toshihiko, Horiba Kazuhiro, Suzuki Takako, Torii Yuka, Yasuda Kazushi, Imanaka-Yoshida Kyoko, Ito Yoshinori

    JOURNAL OF CARDIOLOGY   77 巻 ( 2 ) 頁: 174 - 178   2021年2月

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    記述言語:日本語   出版者・発行元:Journal of Cardiology  

    Background: Myocarditis is an inflammatory disease of the myocardium, which leads to cardiac dysfunction and heart failure. Previous studies have suggested that complex cross-talk between innate and adaptive immune responses is involved in the pathogenesis of acute myocarditis. Immunohistochemistry is the current standard method for the evaluation of infiltrating immune cells, however, it is difficult to investigate and quantify many immune cell populations using this technique. Methods: Endomyocardial biopsy samples of five pediatric patients with myocarditis were analyzed by cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT), a computational method for quantifying cell fractions from tissue gene expression profiles. CIBERSORT results were then compared with immunohistochemistry analyses. Results: Significant results of immune infiltrate deconvolution were obtained in four patients with fulminant myocarditis by CIBERSORT analysis. Among 22 immune cell types, 19 cell types were detected in one or more patients. Activated NK cells were the most prevalent population in two patients, whereas activated memory CD4+ T cells and M2 macrophages were the most prevalent population in one patient each. Overall CIBERSORT results were consistent with those of immunohistochemistry, although some discrepancies were observed. Conclusions: Infiltrating immune cell subsets detected by CIBERSORT analysis can reflect the time course of innate and adaptive immune responses in acute myocarditis. CIBERSORT may have the potential to characterize the detail of infiltrating immune cells in myocardial tissues and provide novel insights into the pathogenesis of acute myocarditis.

    DOI: 10.1016/j.jjcc.2020.08.004

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  7. Viral Reactivations in Children with Aplastic Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Narita Atsushi, Ito Yoshinori, Kawashima Nozomu, Okuno Yusuke, Muramatsu Hideki, Nishio Nobuhiro, Torii Yuka, Kawada Junichi, Kojima Seiji, Takahashi Yoshiyuki

    PEDIATRIC BLOOD & CANCER   67 巻   2020年12月

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    担当区分:筆頭著者   記述言語:日本語  

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  8. Comprehensive Detection of Candidate Pathogens in the Lower Respiratory Tract of Pediatric Patients With Unexpected Cardiopulmonary Deterioration Using Next-Generation Sequencing 国際誌

    Takeuchi Suguru, Kawada Jun-ichi, Horiba Kazuhiro, Yamaguchi Makoto, Okumura Toshihiko, Suzuki Takako, Torii Yuka, Kawabe Shinji, Wada Sho, Ikeyama Takanari, Ito Yoshinori

    PEDIATRIC CRITICAL CARE MEDICINE   21 巻 ( 11 ) 頁: E1026 - E1030   2020年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Pediatric Critical Care Medicine  

    Objectives: Next-generation sequencing has been applied to the investigation of microorganisms in several clinical settings. We investigated the infectious etiologies in respiratory specimens from pediatric patients with unexpected cardiopulmonary deterioration using next-generation sequencing. Design: Retrospective, single-center, observational study. Setting: Tertiary care, a children's hospital. Subjects: The study enrolled a total of 16 pediatric patients with unexpected cardiopulmonary deterioration who were admitted to the PICU. Ten bronchoalveolar lavage fluid and six transtracheal aspirate samples were analyzed. Interventions: None. Measurements and Main Results: RNA libraries were prepared from specimens and analyzed using next-generation sequencing. One or more bacterial/viral pathogens were detected in the bronchoalveolar lavage fluid or transtracheal aspirate specimens from 10 patients. Bacterial and viral coinfection was considered in four cases. Compared with the conventional culture and viral antigen test results, an additional six bacterial and four viral pathogens were identified by next-generation sequencing. Conversely, among 18 pathogens identified by the conventional methods, nine pathogens were detected by next-generation sequencing. Candidate pathogens (e.g., coxsackievirus A6 and Chlamydia trachomatis) were detected by next-generation sequencing in four of 10 patients in whom no causative pathogen had been identified by conventional methods. Conclusions: Our results suggest that viral and bacterial infections are common triggers in unexpected cardiopulmonary deterioration in pediatric patients. Next-generation sequencing has the potential to contribute to clarification of the etiology of pediatric critical illness.

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  9. Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study 国際誌

    Torii Yuka, Horiba Kazuhiro, Hayano Satoshi, Kato Taichi, Suzuki Takako, Kawada Jun-ichi, Takahashi Yoshiyuki, Kojima Seiji, Okuno Yusuke, Ogi Tomoo, Ito Yoshinori

    BMC PEDIATRICS   20 巻 ( 1 ) 頁: 482 - 482   2020年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Pediatrics  

    Background: Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS). Methods: Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences. Results: No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls. Conclusion: No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.

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  10. Association between graft source and response to live-attenuated vaccination in pediatric hematopoietic stem cell transplantation recipients: a single-center retrospective study 国際誌

    Suzuki Takako, Kawada Jun-ichi, Nishikawa Eri, Torii Yuka, Horiba Kazuhiro, Takeuchi Suguru, Okumura Toshihiko, Muramatsu Hideki, Takahashi Yoshiyuki, Ito Yoshinori

    BONE MARROW TRANSPLANTATION   55 巻 ( 9 ) 頁: 1872 - 1874   2020年9月

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    記述言語:日本語   出版者・発行元:Bone Marrow Transplantation  

    DOI: 10.1038/s41409-020-0867-8

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  11. Viral DNA Loads in Various Blood Components of Patients With Epstein-Barr Virus-Positive T-Cell/Natural Killer Cell Lymphoproliferative Diseases 国際誌

    Kawada Jun-ichi, Kamiya Yasuko, Sawada Akihisa, Iwatsuki Keiji, Izutsu Koji, Torii Yuka, Kimura Hiroshi, Ito Yoshinori

    JOURNAL OF INFECTIOUS DISEASES   220 巻 ( 8 ) 頁: 1307 - 1311   2019年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Infectious Diseases  

    To evaluate diagnostic values for Epstein-Barr virus (EBV) DNA loads in different blood components of patients with EBV-positive T-cell/natural killer cell lymphoproliferative diseases, EBV DNA loads were compared among disease categories in each blood component from 59 patients. Plasma viral loads were significantly higher in "active" disease in chronic active EBV infection. EBV DNA was not detected in the plasma from 7 patients in whom EBV DNA was detected in peripheral blood mononuclear cells and whole blood. Diagnostic cutoff values for whole blood EBV DNA loads of patients with chronic active EBV infection compared with those of infectious mononucleosis was 104.2 (15 800) IU/mL.

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  12. Metagenomic analysis using next-generation sequencing of pathogens in bronchoalveolar lavage fluid from pediatric patients with respiratory failure 国際誌

    Takeuchi Suguru, Kawada Jun-ichi, Horiba Kazuhiro, Okuno Yusuke, Okumura Toshihiko, Suzuki Takako, Torii Yuka, Kawabe Shinji, Wada Sho, Ikeyama Takanari, Ito Yoshinori

    SCIENTIFIC REPORTS   9 巻 ( 1 ) 頁: 12909 - 12909   2019年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Next-generation sequencing (NGS) has been applied in the field of infectious diseases. Bronchoalveolar lavage fluid (BALF) is considered a sterile type of specimen that is suitable for detecting pathogens of respiratory infections. The aim of this study was to comprehensively identify causative pathogens using NGS in BALF samples from immunocompetent pediatric patients with respiratory failure. Ten patients hospitalized with respiratory failure were included. BALF samples obtained in the acute phase were used to prepare DNA- and RNA-sequencing libraries. The libraries were sequenced on MiSeq, and the sequence data were analyzed using metagenome analysis tools. A mean of 2,041,216 total reads were sequenced for each library. Significant bacterial or viral sequencing reads were detected in eight of the 10 patients. Furthermore, candidate pathogens were detected in three patients in whom etiologic agents were not identified by conventional methods. The complete genome of enterovirus D68 was identified in two patients, and phylogenetic analysis suggested that both strains belong to subclade B3, which is an epidemic strain that has spread worldwide in recent years. Our results suggest that NGS can be applied for comprehensive molecular diagnostics as well as surveillance of pathogens in BALF from patients with respiratory infection.

    DOI: 10.1038/s41598-019-49372-x

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  13. Serological screening of immunoglobulin M and immunoglobulin G during pregnancy for predicting congenital cytomegalovirus infection 国際誌

    Torii Yuka, Yoshida Shigeru, Yanase Yoichiro, Mitsui Takashi, Horiba Kazuhiro, Okumura Toshihiko, Takeuchi Suguru, Suzuki Takako, Kawada Jun-ichi, Kotani Tomomi, Yamashita Mamoru, Ito Yoshinori

    BMC PREGNANCY AND CHILDBIRTH   19 巻 ( 1 ) 頁: 205 - 205   2019年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Pregnancy and Childbirth  

    Background: Cytomegalovirus (CMV) is one of the most frequent pathogens for congenital infections. Most cases of congenital CMV infection (cCMV) are asymptomatic at birth, but sensorineural hearing loss (SNHL) or neurodevelopmental delay can appear later in childhood. This prospective study examined the practicability of serological screening for anti-CMV immunoglobulin (Ig) G and anti-CMV IgM in pregnant women. Methods: A total of 11,753 pregnant women were examined for CMV IgG and CMV IgM during the first or second trimester. When IgM was positive, IgG was reevaluated more than two weeks later. When IgG was negative, IgG was reevaluated in the second or third trimester. All neonates from mothers with positive/borderline IgM or IgG seroconversion underwent polymerase chain reaction assay for CMV using urine samples to diagnose cCMV. Levels of IgG and IgM were compared between mothers with and without cCMV. Receiver operating characteristic (ROC) curves for IgM titers were analyzed. Results: Eight of 500 neonates (1.6%) born from mothers with positive IgG and positive IgM, and 3 of 13 neonates (23.1%) born from mothers with IgG seroconversion were diagnosed with cCMV. Neither IgM titers nor IgG titers differed significantly between cCMV and non-cCMV groups. The area under the ROC curve was 0.716 and the optimal cut-off for IgM was 7.28 index (sensitivity = 0.625, specificity = 0.965, positive predictive value = 0.238, negative predictive value = 0.993). Titers of IgG were not frequently elevated in pregnant women with positive IgM during the observation period, including in those with cCMV. All 11 cCMV cases were asymptomatic at birth and none had shown SNHL or developmental delay as of the last regular visit (mean age, 40 months). Conclusions: Seroconversion of CMV IgG and high-titer IgM during early pregnancy are predictors of cCMV. High IgM titer (> 7.28 index) is a predictor despite relatively low sensitivity. Levels of IgG had already plateaued at first evaluation in mothers with cCMV. Maternal screening offered insufficient positive predictive value for diagnosing cCMV, but allowed identifying asymptomatic cCMV cases in an early stage.

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  14. Identification of potential pathogenic viruses in patients with acute myocarditis using next-generation sequencing 国際誌

    Takeuchi Suguru, Kawada Jun-ichi, Okuno Yusuke, Horiba Kazuhiro, Suzuki Takako, Torii Yuka, Yasuda Kazushi, Numaguchi Atsushi, Kato Taichi, Takahashi Yoshiyuki, Ito Yoshinori

    JOURNAL OF MEDICAL VIROLOGY   90 巻 ( 12 ) 頁: 1814 - 1821   2018年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Medical Virology  

    Myocarditis is an inflammatory disease of the myocardium and leads to cardiac dysfunction and heart failure. Although viral infections are considered to be the most common etiology of myocarditis, the identification of the causative virus is still challenging. Recently, next-generation sequencing (NGS) has been applied in the diagnosis of infectious diseases. The aim of the current study was to comprehensively analyze potential pathogenic microorganisms using NGS in the sera of patients with myocarditis. Twelve pediatric and five adult patients hospitalized for acute myocarditis were included. Serum samples in the acute phase were obtained and analyzed using NGS to detect pathogen-derived DNA and RNA. Viral sequence reads were detected in 7 (41%) of the 17 myocarditis patients by NGS. Among these patients, detection of Epstein-Barr virus, human parvovirus B19, torque teno virus, and respiratory syncytial virus reads by NGS was consistent with polymerase chain reaction or antigen test results in one patient each. A large number of human pegivirus reads were detected from one patient by RNA sequencing; however, its pathogenicity to human is unknown. Conversely, the number of detected virus-derived reads was small in most cases, and the pathophysiological role of these viruses remains to be clarified. No significant bacterial or fungal reads other than normal bacterial flora was detected. These data indicate that comprehensive detection of virus-derived DNA and RNA using NGS can be useful for the identification of potential pathogenic viruses in myocarditis.

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  15. Risk Factors for Viral Infections in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Narita Atsushi, Ito Yoshinori, Torii Yuka, Kawada Jun-Ichi, Miwata Shunsuke, Narita Kotaro, Kitazawa Hironobu, Hamada Motoharu, Kataoka Shinsuke, Ichikawa Daisuke, Ito Rieko, Murakami Norihiro, Kojima Daiei, Suzuki Kyogo, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Muramatsu Hideki, Hama Asahito, Kojima Seiji, Takahashi Yoshiyuki

    BONE MARROW TRANSPLANTATION   53 巻   頁: 588 - 589   2018年9月

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  16. Congenital Cytomegalovirus Pneumonitis and Treatment Response Evaluation Using Viral Load during Ganciclovir Therapy: a Case Report

    Lee-Yoshimoto Minsoo, Goishi Keiji, Torii Yuka, Ito Yoshinori, Ono Hiroya, Mori Tomoko, Kashiwa Naoyuki, Hosokawa Shinichi, Shichino Hiroyuki

    Japanese Journal of Medical Science and Biology   71 巻 ( 4 ) 頁: 309 - 311   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:国立感染症研究所 Japanese Journal of Infectious Diseases 編集委員会  

    Cytomegalovirus (CMV) is the most common cause of congenital infection. Pneumonitis is considered to be a rare manifestation although congenital CMV infection presents with various non-specific findings. Ganciclovir and valganciclovir are beneficial for improving neurodevelopmental se-quelae and hearing outcomes of congenital CMV infection; however, treatment response evaluation is not well reported. We report a female case of congenital CMV infection presenting with pneumonitis, menin-goencephalitis, and chorioretinitis. She was treated with intravenous ganciclovir for 6 weeks, and clinical features improved. Measurement of the CMV genome load by real-time polymerase chain reaction assay was performed during treatment. After the administration of ganciclovir, the CMV genome was not detected in the blood and levels decreased gradually in the urine. Physicians should consider the possibility of congenital CMV infection in neonates who present with respiratory distress. Furthermore, measurement of the CMV genome load in blood and urine may be useful for evaluating treatment response.

    DOI: 10.7883/yoken.jjid.2017.577

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  17. Antitumor effects of duvelisib on Epstein-Barr virus-associated lymphoma cells 国際誌

    Kawada Jun-ichi, Ando Shotaro, Torii Yuka, Watanabe Takahiro, Sato Yoshitaka, Ito Yoshinori, Kimura Hiroshi

    CANCER MEDICINE   7 巻 ( 4 ) 頁: 1275 - 1284   2018年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Medicine  

    Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in EBV-associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV-associated lymphoma cell lines. We found that the PI3K/Akt signaling pathway was activated in most of the B and T cell lymphoma cell lines tested. Additionally, duvelisib treatment inhibited cellular growth in the tested cell lines. Overall, B cell lines were more susceptible to duvelisib than T and NK cell lines in vitro regardless of EBV infection. However, the additional influence of duvelisib on the tumor microenvironment was not assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in EBV-positive and -negative B cell lines, but not in T cell lines. Furthermore, duvelisib treatment reduced the expression of EBV lytic genes (BZLF1 and gp350/220) in EBV-positive B cell lines, suggesting that duvelisib suppresses the lytic cycle of EBV induced by B cell receptor signaling. However, duvelisib did not induce a remarkable change in the expression of EBV latent genes. These results may indicate that there is therapeutic potential for duvelisib administration in the treatment of EBV-associated B cell lymphomas and other B cell malignancies.

    DOI: 10.1002/cam4.1311

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  18. Comprehensive detection of pathogens in immunocompromised children with bloodstream infections by next-generation sequencing 国際誌

    Horiba Kazuhiro, Kawada Jun-ichi, Okuno Yusuke, Tetsuka Nobuyuki, Suzuki Takako, Ando Shotaro, Kamiya Yasuko, Torii Yuka, Yagi Tetsuya, Takahashi Yoshiyuki, Ito Yoshinori

    SCIENTIFIC REPORTS   8 巻 ( 1 ) 頁: 3784 - 3784   2018年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at disease onset. Bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients. Bacterial reads per million reads of the sequence depth (BR) > 200 and relative importance values of the dominant bacteria (P1) > 0.5 were employed to determine causative pathogens. Causative pathogens were detected using these criteria in 7 of 12 patients with BSI. Additionally, causative bacteria were detected in the plasma/serum at 7 days before disease onset in two patients with catheter-related BSI. Causative pathogens, including virus, were identified in three patients with suspected BSI. Lastly, a total of 62 resistance genes were detected by NGS. In conclusion, NGS is a new method to identify causative microorganisms in BSI and may predict BSI in some patients.

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  19. Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing 国際誌

    Suzuki Takako, Kawada Jun-ichi, Okuno Yusuke, Hayano Satoshi, Horiba Kazuhiro, Torii Yuka, Takahashi Yoshiyuki, Umetsu Syuichiro, Sogo Tsuyoshi, Inui Ayano, Ito Yoshinori

    JOURNAL OF CLINICAL VIROLOGY   96 巻   頁: 67 - 72   2017年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Clinical Virology  

    Background Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. Objectives To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. Study design To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. Results Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. Conclusions This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF.

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  20. Metabolome analysis reveals the association between the kynurenine pathway and human herpesvirus 6 encephalopathy in immunocompetent children

    Torii Yuka, Kawano Yoshihiko, Sato Hajime, Fujimori Tamaki, Sasaki Kazunori, Kawada Jun-ichi, Takikawa Osamu, Lim Chai K., Guillemin Gilles J., Ohashi Yoshiaki, Ito Yoshinori

    METABOLOMICS   13 巻 ( 11 )   2017年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Metabolomics  

    Introduction: Human herpesvirus 6 (HHV-6) is the second most common causative pathogen of acute encephalopathy in immunocompetent children in Japan. Identification of biomarkers associated the pathophysiology is desirable to monitor disease severity, progression, and prognosis. Objectives: To investigate potential biomarkers for HHV-6 encephalopathy, serum metabolome profiling was analyzed and candidate metabolites were investigated the function in the diseases. Methods: Pediatric patients with HHV-6 encephalopathy (n = 8), febrile seizure (n = 20), and febrile infection without febrile seizure (n = 7) were enrolled in this study, and serum metabolites were identified and quantified. For further analysis, serum samples of HHV-6 infected patients were analyzed by absolute quantification assay for kynurenine (KYN) and quinolinic acid (QUIN) in a total of 38 patients with or without encephalopathy. An in vitro blood–brain barrier (BBB) model was used to evaluate the effect of KYN and QUIN on BBB integrity because BBB damage induces brain edema. Results: Metabolome profiling identified 159 metabolites in serum samples. The levels of KYN and QUIN, which belong to the tryptophan-KYN pathway, were significantly higher in the HHV-6 encephalopathy group than the other two groups. When quantified in the larger patient group, remarkably high levels of KYN and QUIN were observed exclusively in the encephalopathy group. Trans-endothelial electrical resistance of the BBB model was significantly decreased after QUIN treatment in culture. Conclusion: Metabolome analysis revealed that KYN and QUIN may be associated with the pathophysiology of HHV-6 encephalopathy. In particular, QUIN may damage BBB integrity.

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  21. Epstein-Barr virus infection-induced inflammasome activation in human monocytes 国際誌

    Torii Yuka, Kawada Jun-ichi, Murata Takayuki, Yoshiyama Hironori, Kimura Hiroshi, Ito Yoshinori

    PLOS ONE   12 巻 ( 4 ) 頁: e0175053   2017年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS ONE  

    Inflammasomes are cytoplasmic sensors that regulate the activity of caspase-1 and the secretion of interleukin-1β (IL-1β) or interleukin-18 (IL-18) in response to foreign molecules, including viral pathogens. They are considered to be an important link between the innate and adaptive immune responses. However, the mechanism by which inflammasome activation occurs during primary Epstein-Barr virus (EBV) infection remains unknown. Human B lymphocytes and epithelial cells are major targets of EBV, although it can also infect a variety of other cell types. In this study, we found that EBV could infect primary human monocytes and the monocyte cell line, THP-1, inducing inflammasome activation. We incubated cell-free EBV with THP-1 cells or primary human monocytes, then confirmed EBV infection using confocal microscopy and flow cytometry. Lytic and latent EBV genes were detected by real-time RT-PCR in EBV-infected monocytes. EBV infection of THP-1 cells and primary human monocytes induced caspase-dependent IL-1β production, while EBV infection of B-cell or T-cell lines did not induce IL-1β production. To identify the sensor molecule responsible for inflammasome activation during EBV infection, we examined the mRNA and the protein levels of NLR family pyrin domain-containing 3(NLRP3), absent in melanoma 2(AIM2), and interferon-inducible protein 16 (IFI16). Increased AIM2 levels were observed in EBV-infected THP-1 cells and primary human monocytes, whereas levels of IFI16 and NLRP3 did not show remarkable change. Furthermore, knockdown of AIM2 by small interfering RNA attenuated caspase-1 activation. Taken together, our results suggest that EBV infection of human monocytes induces caspase-1-dependent IL-1β production, and that AIM2, acting as an inflammasome, is involved in this response.

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  22. Analysis of circulating human and viral microRNAs in patients with congenital cytomegalovirus infection

    Kawano Y., Kawada J., Kamiya Y., Suzuki M., Torii Y., Kimura H., Ito Y.

    JOURNAL OF PERINATOLOGY   36 巻 ( 12 ) 頁: 1101 - 1105   2016年12月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:Journal of Perinatology  

    Objective:Cytomegalovirus (CMV) is the most common cause of congenital infection and can cause neurodevelopmental disabilities, although a majority of patients are asymptomatic. Biomarkers associated with disease severity would be desirable to distinguish asymptomatic from mildly symptomatic patients who may benefit from antiviral treatment. MicroRNAs (miRNAs) are noncoding RNAs that may have the potential to serve as biomarkers.Study Design:Thirteen infants with congenital CMV infection were enrolled, and plasma levels of 11 human- and 3 CMV-encoded miRNAs were quantitated by real-time PCR. Plasma levels of miRNAs and their associations with clinical features were evaluated.Results:The levels of miR-183-5p and miR-210-3p were significantly higher in patients with congenital CMV infection than in control infants, whereas no significant associations between levels of miRNAs and clinical features of congenital CMV infection were observed.Conclusion:Plasma miRNAs could be associated with the pathogenesis of congenital CMV infection and could be used as disease biomarkers.

    DOI: 10.1038/jp.2016.157

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  23. Primary psoas abscess caused by group A streptococcus in a child: Case report with microbiologic findings 国際誌

    Kamiya Yasuko, Hasegawa Tadao, Takegami Yasuhiko, Horiba Kazuhiro, Ando Shotaro, Torii Yuka, Kidokoro Hiroyuki, Kato Taichi, Natsume Jun, Kawada Jun-Ich, Ito Yoshinori

    JOURNAL OF INFECTION AND CHEMOTHERAPY   22 巻 ( 12 ) 頁: 811 - 814   2016年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Infection and Chemotherapy  

    Primary abscess of the iliopsoas muscle in children is uncommon, especially due to Streptococcus pyogenes (group A streptococcus: GAS), which causes a variety of diseases ranging from pharyngitis to invasive life-threatening infection. We present primary iliopsoas abscess in a nine-year-old boy presenting with fever, mild disturbance of consciousness, limp, and pain in the right loin. Magnetic resonance imaging and isolation of GAS from both blood and abscess samples led us to the confirmative diagnosis. The patient recovered after treatment comprising drainage and intravenous antibiotics. The CovRS system is one of the best-characterized systems with two-component signal transduction in the GAS, and mutations in covRS induce overproduction of various virulence factors that play a crucial role in invasive GAS infection. RopB, also known as a GAS regulator, influences the expression of multiple regulatory networks to coregulate virulence factor expression in GAS. In the present case, sequence analysis revealed the isolated GAS as emm type 6 with alterations in covS, whereas the covR and ropB genes were intact. The covS alterations might have influenced the virulence of the strain causing this severe GAS infection.

    DOI: 10.1016/j.jiac.2016.06.011

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  24. Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells 国際誌

    Ando Shotaro, Kawada Jun-ichi, Watanabe Takahiro, Suzuki Michio, Sato Yoshitaka, Torii Yuka, Asai Masato, Goshima Fumi, Murata Takayuki, Shimizu Norio, Ito Yoshinori, Kimura Hiroshi

    ONCOTARGET   7 巻 ( 47 ) 頁: 76793 - 76805   2016年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oncotarget  

    Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

    DOI: 10.18632/oncotarget.12529

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  25. Identification of Viruses in Cases of Pediatric Acute Encephalitis and Encephalopathy Using Next-Generation Sequencing 国際誌

    Kawada Jun-ichi, Okuno Yusuke, Torii Yuka, Okada Ryo, Hayano Satoshi, Ando Shotaro, Kamiya Yasuko, Kojima Seiji, Ito Yoshinori

    SCIENTIFIC REPORTS   6 巻   頁: 33452 - 33452   2016年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Acute encephalitis/encephalopathy is a severe neurological syndrome that is occasionally associated with viral infection. Comprehensive virus detection assays are desirable because viral pathogens have not been identified in many cases. We evaluated the utility of next-generation sequencing (NGS) for detecting viruses in clinical samples of encephalitis/encephalopathy patients. We first determined the sensitivity and quantitative performance of NGS by comparing the NGS-determined number of sequences of human herpesvirus-6 (HHV-6) in clinical serum samples with the HHV-6 load measured using real-time PCR. HHV-6 was measured as it occasionally causes neurologic disorders in children. The sensitivity of NGS for detection of HHV-6 sequences was equivalent to that of real-time PCR, and the number of HHV-6 reads was significantly correlated with HHV-6 load. Next, we investigated the ability of NGS to detect viral sequences in 18 pediatric patients with acute encephalitis/encephalopathy of unknown etiology. A large number of Coxsackievirus A9 and mumps viral sequences were detected in the cerebrospinal fluid of 2 and 1 patients, respectively. In addition, Torque teno virus and Pepper mild mottle viral sequences were detected in the sera of one patient each. These data indicate that NGS is useful for detection of causative viruses in patients with pediatric encephalitis/encephalopathy.

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  26. Quantitative metabolome profiling reveals the involvement of the kynurenine pathway in influenza-associated encephalopathy

    Torii Yuka, Kawano Yoshihiko, Sato Hajime, Sasaki Kazunori, Fujimori Tamaki, Kawada Jun-ichi, Takikawa Osamu, Lim Chai K., Guillemin Gilles J., Ohashi Yoshiaki, Ito Yoshinori

    METABOLOMICS   12 巻 ( 5 )   2016年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Metabolomics  

    Introduction: Influenza-associated encephalopathy is a serious complication of influenza and is the most common form of acute encephalitis/encephalopathy in Japan. The number of reports from other countries is increasing, reflecting international recognition and concern. Objectives: Identification of a specific biomarker could provide important clues about the pathophysiology of influenza-associated encephalopathy. Methods: During the 2009–2011 flu seasons, 34 pediatric patients hospitalized with influenza complications, including influenza-associated encephalopathy, were enrolled in the study. Serum samples were collected during the acute and convalescent phases of disease. Patients were classified into encephalopathy (n = 12) and non-encephalopathy (n = 22) groups. Serum metabolites were identified and quantified by capillary electrophoresis coupled with time-of-flight mass spectrometry. Quantified data were evaluated for comparative analysis. Subsequently, a total of 55 patients with or without encephalopathy were enrolled for absolute quantification of serum kynurenine and quinolinic acid. Results: Based on m/z values and migration times, 136 metabolites were identified in serum samples. During the acute phase of disease, three metabolites (succinic acid, undecanoic acid, and kynurenine) were significantly higher, and two other metabolites (decanoic acid and cystine) were significantly lower, in the encephalopathy group compared to the non-encephalopathy group (p = 0.012, 0.022, 0.044, 0.038, 0.046, respectively). In a larger patient group, serum kynurenine and its downstream product in tryptophan metabolism, quinolinic acid, a known neurotoxin, were significantly higher in the encephalopathy than the non-encephalopathy without febrile seizure group. Conclusion: Comprehensive metabolite profiles revealed five metabolites as potential biomarkers for influenza-associated encephalopathy; the tryptophan–kynurenine metabolic process could be associated with its pathophysiology.

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  27. Correlation of rabbit antithymocyte globulin serum levels and clinical outcomes in children who received hematopoietic stem cell transplantation from an alternative donor 国際誌

    Elmahdi Shaimaa, Muramatsu Hideki, Narita Atsushi, Torii Yuka, Ismael Olfat, Kawashima Nozomu, Okuno Yusuke, Sekiya Yuko, Xu Yinyan, Wang Xinan, Hama Asahito, Ito Yoshinori, Takahashi Yoshiyuki, Kojima Seiji

    PEDIATRIC TRANSPLANTATION   20 巻 ( 1 ) 頁: 105 - 113   2016年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Pediatric Transplantation  

    We analyzed the correlation between rabbit ATG (rATG) serum levels and clinical outcomes in 37 children who received rATG at a total dose of 10 or 15 mg/kg during HSCT conditioning from an alternative donor. Fourteen patients had advanced malignant diseases, 13 had severe AA, and 10 had inherited disorders. Complete engraftment was achieved in all patients, and no rejection occurred. The cumulative incidence of grades II-IV acute GVHD and extensive chronic GVHD was 27% (95% CI, 12.5-39.6%) and 8.1% (95% CI, 0-23.1%), respectively. Multivariate analysis identified lower rATG levels at week 4 as an independent risk factor in the development of grades II-IV acute GVHD (p = 0.037). Serious infections were not observed in any patient following HSCT. No correlation was found between EBV reactivation and rATG levels at week 2 and week 4 after HSCT. Furthermore, no correlation was found between relapse and rATG levels two and four wk post-transplantation. The probability of five-yr OS among patients was 70.3% (95% CI, 59.8-79.2%). Our results suggest that targeted rATG administration may protect patients from severe acute GVHD without increasing the risk of EBV reactivation or relapse.

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  28. Fulminant adenovirus hepatitis after hematopoietic stem cell transplant: Retrospective real-time PCR analysis for adenovirus DNA in two cases 国際誌

    Kawashima N., Muramatsu H., Okuno Y., Torii Y., Kawada J.i., Narita A., Nakanishi K., Hama A., Kitamura A., Asai N., Nakamura S., Takahashi Y., Ito Y., Kojima S.

    Journal of Infection and Chemotherapy   21 巻 ( 12 ) 頁: 857 - 63   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Infection and Chemotherapy  

    Background: Viral infection is one of the major causes of mortality in patients undergoing hematopoietic stem cell transplant (HSCT). Systemic infection of adenovirus (AdV) has emerged as a not uncommon viral infection with significant morbidity and mortality as with cytomegalovirus and Epstein-Barr virus infection. Routine surveillance for these viruses has become a clinical practice and subsequent preemptive therapy improves patients' outcomes; however, the effectiveness of preemptive therapy for AdV has not been fully investigated in patients with a lethal form of AdV infection. Methods: Sequential AdV loads were retrospectively analyzed in children with fulminant AdV hepatitis after HSCT. Results: The AdV DNA became detectable (1 × 104 copies/mL) as early as 2 weeks after HSCT. These levels reached >1 × 108 copies/mL at the onset of fulminant hepatitis. However, we determined that γ-glutamyltransferase levels were elevated to >100 IU/L at least 2 weeks before the diagnosis of hepatitis. Conclusions: Our observation raises the possibility that elevated γ-glutamyltransferase could be a sentinel marker for AdV hepatitis, which prompts elaborated monitoring of AdV load and targeted treatment.

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  29. Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis 国際誌

    Kamiya Yasuko, Kawada Jun-ichi, Kawano Yoshihiko, Torii Yuka, Kawabe Shinji, Iwata Naomi, Ito Yoshinori

    CLINICAL RHEUMATOLOGY   34 巻 ( 10 ) 頁: 1705 - 1712   2015年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical Rheumatology  

    MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression of targeted mRNAs, which are important in the pathogenesis of autoimmune diseases. MiRNAs may have the potential to serve as biomarkers of disease. We evaluated serum levels of selected miRNAs and their associations with disease activity in juvenile idiopathic arthritis (JIA). Sera and peripheral blood leukocytes were collected from patients with JIA (8 systemic onset, 16 polyarthritis) and healthy controls. Levels of miR-16, miR-132, miR-146a, miR-155, and miR-223 were quantified. Levels of miR-223 in sera were significantly higher in patients in the active phase of systemic onset JIA than in controls. MiRNAs of peripheral blood leukocytes did not exhibit any difference between patients with JIA and controls. In both systemic onset JIA and polyarthritis patients, levels of miR-223 and miR-16 correlated with erythrocyte sedimentation rate and matrix metalloproteinase-3, respectively. MiR-146a and miR-223 in polyarthritis showed correlations with matrix metalloproteinase-3. Expressions of miRNAs were altered in patients with JIA. Serum levels of miR-223 may be a potential disease biomarker. Investigation of miRNAs could be helpful in understanding the pathogenesis of JIA and could aid in the identification of additional disease biomarkers.

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  30. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening 国際誌

    Kawada Jun-ichi, Torii Yuka, Kawano Yoshihiko, Suzuki Michio, Kamiya Yasuko, Kotani Tomomi, Kikkawa Fumitaka, Kimura Hiroshi, Ito Yoshinori

    JOURNAL OF CLINICAL VIROLOGY   65 巻   頁: 41 - 45   2015年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Clinical Virology  

    Background: Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. Objectives: The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Study design: Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Results: Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Conclusions: Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL.

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  31. Immunogenicity of inactivated seasonal influenza vaccine in adult and pediatric liver transplant recipients over two seasons 国際誌

    Suzuki Michio, Torii Yuka, Kawada Jun-ichi, Kimura Hiroshi, Kamei Hideya, Onishi Yasuharu, Kaneko Kenitiro, Ando Hisami, Kiuchi Tetsuya, Ito Yoshinori

    MICROBIOLOGY AND IMMUNOLOGY   57 巻 ( 10 ) 頁: 715 - 722   2013年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Microbiology and Immunology  

    Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

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  32. Risk factors for poor outcome in congenital cytomegalovirus infection and neonatal herpes on the basis of a nationwide survey in Japan 国際誌

    Ito Yoshinori, Kimura Hiroshi, Torii Yuka, Hayakawa Masahiro, Tanaka Toshihiro, Tajiri Hitoshi, Yoto Yuko, Tanaka-Taya Keiko, Kanegane Hirokazu, Nariai Akiyoshi, Sakata Hiroshi, Tsutsumi Hiroyuki, Oda Megumi, Yokota Shumpei, Morishima Tsuneo, Moriuchi Hiroyuki

    PEDIATRICS INTERNATIONAL   55 巻 ( 5 ) 頁: 566 - 571   2013年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Pediatrics International  

    Background: Congenital cytomegalovirus (CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. Methods: A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. Results: Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction (IUGR) or other specific findings on fetal ultrasonography (US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (<60 mg/kg per day). Conclusions: This secondary survey has identified the risk factors associated with outcome and important issues in diagnosis and treatment of two mother-to-child infections: congenital CMV and neonatal herpes, in Japan. © 2013 Japan Pediatric Society.

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  33. Plasma Viral MicroRNA Profiles Reveal Potential Biomarkers for Chronic Active Epstein-Barr Virus Infection 国際誌

    Kawano Yoshihiko, Iwata Seiko, Kawada Jun-ichi, Gotoh Kensei, Suzuki Michio, Torii Yuka, Kojima Seiji, Kimura Hiroshi, Ito Yoshinori

    JOURNAL OF INFECTIOUS DISEASES   208 巻 ( 5 ) 頁: 771 - 779   2013年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Infectious Diseases  

    Background. Chronic active Epstein-Barr virus (CAEBV) infection has high mortality and morbidity, and biomarkers for disease severity and prognosis are required. MicroRNAs (miRNAs) are small noncoding RNAs, and EBV encodes multiple miRNAs. Because plasma contains sufficiently stable miRNAs, circulating EBV-associated miRNA profiles were investigated as novel biomarkers in CAEBV infection.Methods. Plasma miRNA expression was assessed for 12 miRNAs encoded within 2 EBV open reading frames (BART and BHRF). Expression levels were investigated in 19 patients with CAEBV infection, 14 patients with infectious mononucleosis, and 11 healthy controls. Relative expression levels of plasma miRNAs were determined by TaqMan probe-based quantitative assay.Results. Plasma miR-BART1-5p, 2-5p, 5, and 22 levels in patients with CAEBV infection were significantly greater than those in patients with infectious mononucleosis and in controls. Plasma miR-BART2-5p, 4, 7, 13, 15, and 22 levels were significantly elevated in patients with CAEBV infection with systemic symptoms, compared with levels in patients with no systemic symptoms. The levels of miR-BART2-5p, 13, and 15 showed clinical cutoff values associated with specific clinical conditions, in contrast to plasma EBV loads.Conclusions. Levels of specific plasma EBV miRNAs were elevated differentially in patients with CAEBV infection. Several EBV miRNAs, particularly miR-BART2-5p, 13, and 15, are potentially biomarkers of disease severity or prognosis. © 2013 The Author.

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  34. CLINICOEPIDEMIOLOGIC STATUS OF MOTHER-TO-CHILD INFECTIONS: A NATIONWIDE SURVEY IN JAPAN 国際誌

    Torii Yuka, Kimura Hiroshi, Ito Yoshinori, Hayakawa Masahiro, Tanaka Toshihiro, Tajiri Hitoshi, Yoto Yuko, Tanaka-Taya Keiko, Kanegane Hirokazu, Nariai Akiyoshi, Sakata Hiroshi, Tsutsumi Hiroyuki, Oda Megumi, Yokota Shumpei, Morishima Tsuneo, Moriuchi Hiroyuki

    PEDIATRIC INFECTIOUS DISEASE JOURNAL   32 巻 ( 6 ) 頁: 699 - 701   2013年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Pediatric Infectious Disease Journal  

    We conducted a nationwide survey of the present status of 10 representative mother-to-child infections in Japan. Congenital syphilis, vertical human T-cell leukemia virus type 1 infection, congenital rubella and vertical HIV infection, for which effective preventative strategies have been established, were rare. Cytomegalovirus was the most common congenital pathogen in Japan, although most infants with congenital cytomegalovirus infection may remain undiagnosed. Copyright © 2013 by Lippincott Williams & Wilkins.

    DOI: 10.1097/INF.0b013e3182897c36

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  35. Remission of juvenile idiopathic arthritis with primary Epstein-Barr virus infection 国際誌

    Kawada Jun-ichi, Ito Yoshinori, Torii Yuka, Kimura Hiroshi, Iwata Naomi

    RHEUMATOLOGY   52 巻 ( 5 ) 頁: 956 - 958   2013年5月

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    記述言語:日本語   出版者・発行元:Rheumatology (United Kingdom)  

    DOI: 10.1093/rheumatology/kes299

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  36. Causes of vertical transmission of hepatitis B virus under the at-risk prevention strategy in Japan 国際誌

    Torii Yuka, Kimura Hiroshi, Hayashi Kazuhiko, Suzuki Michio, Kawada Jun-ichi, Kojima Seiji, Katano Yoshiaki, Goto Hidemi, Ito Yoshinori

    MICROBIOLOGY AND IMMUNOLOGY   57 巻 ( 2 ) 頁: 118 - 121   2013年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Microbiology and Immunology  

    The number of hepatitis B virus (HBV) carrier babies has decreased markedly since the introduction in Japan of an "at-risk" strategy for preventing HBV infection. However, elimination of HBV infection from our country appears difficult. To clarify the limitations of the at-risk strategy for preventing vertical transmission of HBV, causes of vertical transmission in a single hospital were retrospectively analyzed. The following causes were presumed in 17 carrier pediatric cases: five patients had prenatal HBV infection, HBV infection during/after the immunization program was confirmed in five cases, two patients had prenatal infection or infection during the immunization program and three cases were caused by human error (by the patients' guardians). Because their mothers were HBV-negative at screening and only developed acute hepatitis B in the perinatal period, another two cases (Cases 3 and 10) did not undergo immunization because they were not subjects of the at-risk strategy. Sequence analyses in ten patients revealed genotype C (subgenotype, C2/Ce) in nine cases and genotype A (subgenotype, A2/Ae) in one case (Case 3). In Japan, HBV subgenotype Ae has recently been found more frequently among sexually active men with acute hepatitis. There are concerns that horizontal transmission of HBV from these men to their pregnant partners could increase. These data suggest clear limitations to the at-risk strategy in Japan and the possibility that the increase in genotype A may influence vertical transmission of HBV. © 2012 The Societies and Wiley Publishing Asia Pty Ltd.

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  37. Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children 国際誌

    Ito Yoshinori, Torii Yuka, Ohta Rieko, Imai Masaki, Hara Shinya, Kawano Yoshihiko, Matsubayashi Tadashi, Inui Ayano, Yoshikawa Tetsushi, Nishimura Naoko, Ozaki Takao, Morishima Tsuneo, Kimura Hiroshi

    CYTOKINE   56 巻 ( 2 ) 頁: 180 - 187   2011年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cytokine  

    Background: The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan. Methods: This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients. Results: Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines. Conclusions: Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia. © 2011 Elsevier Ltd.

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  38. Immunogenicity of inactivated 2009 H1N1 influenza vaccine in pediatric liver transplant recipients 国際誌

    Torii Yuka, Kimura Hiroshi, Ochi Nobuhiko, Kaneko Kenitiro, Ando Hisami, Kiuchi Tetsuya, Ito Yoshinori

    VACCINE   29 巻 ( 25 ) 頁: 4187 - 4189   2011年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Vaccine  

    To assess the safety and immunogenicity of 2009 H1N1 influenza vaccination, 13 pediatric liver transplant recipients and 31 immunocompetent controls received inactivated influenza vaccine without adjuvant according to Japanese guidelines. Serious adverse events and acute allograft rejections were not observed in participants. Seroprotection rates (hemagglutinin-inhibition (HI) antibody titer ≥ 1:40) were 53.8% among recipients and 58.1% among controls (p= 0.797). Seroconversion rates (4-fold or more HI antibody rise) were 46.2% for the recipient group and 51.6% for the control group (p= 0.741). Geometric mean titers were elevated after vaccination in both groups. In comparison with the seasonal influenza vaccination, the seroconversion rate for 2009 H1N1 appeared to be higher than that for seasonal influenza antigens, and the seroprotection rate for 2009 H1N1 clearly increased after vaccination. These findings suggest that pediatric liver transplant patients may respond safely to inactivated 2009 H1N1 influenza vaccines in a manner similar to immunocompetent children. © 2011 Elsevier Ltd.

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  39. Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza 国際誌

    Ohta Rieko, Torii Yuka, Imai Masaki, Kimura Hiroshi, Okada Noriko, Ito Yoshinori

    MICROBIOLOGY AND IMMUNOLOGY   55 巻 ( 3 ) 頁: 191 - 198   2011年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Microbiology and Immunology  

    Anaphylatoxins (C5a, C4a, and C3a) are fragments of activated complement and are leading mediators of the inflammatory response for controlling viral infection. However, an excessive response may increase the severity of infectious diseases. Serum concentrations of proinflammatory mediators, including cytokines, high-mobility group box 1 and anaphylatoxins, were measured in pediatric 2009 H1N1 influenza patients in order to investigate the pathology of this new influenza. The concentrations of all three anaphylatoxins were significantly enhanced by 2009 H1N1 influenza infection. However, there were no significant differences in anaphylatoxin concentrations between 2009 H1N1 influenza patients with and without severe complications during the early stages of the disease. C3a concentrations dropped significantly during the recovery phase, whereas there were no significant differences between the acute and recovery phases in C5a and C4a concentrations. There was a correlation between C5a and IL-2. C4a was associated with IL-1ra, eotaxin, MCP-1, PDGFbb, and VEGF. C3a was correlated with IL-2 and IFN-γ. Taken together, these findings indicate that complement activation occurs in patients infected with 2009 H1N1 influenza virus and demonstrate that anaphylatoxins are involved in increased production of proinflammatory mediators in this new influenza. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

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  40. Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome

    Torii Yuka, Yagasaki Hiroshi, Tanaka Hidenori, Mizuno Seiji, Nishio Nobuhiro, Muramatsu Hideki, Hama Asahito, Takahashi Yoshiyuki, Kojima Seiji

    INTERNATIONAL JOURNAL OF HEMATOLOGY   90 巻 ( 2 ) 頁: 174 - 176   2009年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Hematology  

    Kabuki syndrome (KS) is often associated with autoimmune abnormalities, such as idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, leukoplakia and thyroiditis, as well as congenital anomalies. We herein present a KS patient with refractory ITP who achieved durable and complete remission in response to a total of four once-monthly infusions of rituximab. KS patients are often more susceptible to infection, so splenectomy should be avoided. Therefore, rituximab therapy is an alternative option for KS patients with ITP who fail to respond to first-line therapy. © 2009 The Japanese Society of Hematology.

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▼全件表示

MISC 1

  1. Discussion & Education B型肝炎における母子感染予防のためのワクチン療法

    伊藤 嘉規, 鳥居 ゆか, 川田 潤一  

    感染症道場3 巻 ( 2 ) 頁: 16 - 23   2014年6月

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    記述言語:日本語   出版者・発行元:メディカルレビュー社  

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    その他リンク: http://search.jamas.or.jp/link/ui/2014246646

科研費 3

  1. 次世代シーケンスによる小児急性脳症の血液及び髄液エクソソームマイクロRNA解析

    研究課題/研究課題番号:18K16172  2018年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    鳥居 ゆか

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    けいれん重積型(二相性)急性脳症(AESD)における脳脊髄液および血清エクソソーム中マイクロRNAの発現解析について次世代シーケンスで検討した。AESD群5例および熱性けいれん症例群5例の脳脊髄液および血清からエクソソームを抽出しエクソソーム中のsmall RNAを次世代シーケンサーにて判読、データベースへ照合した。脳脊髄液からのべ176種類のマイクロRNAが症例あたり平均4,029リード検出され、miR381-3pの発現が脳症群で有意に上昇していた。血清からのべ663種類のマイクロRNAが症例あたり平均599,470リード検出されたが、2群間で発現に有意差のあるマイクロRNAはなかった。

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  2. Epstein-Barrウイルス感染におけるヒト白血球でのインフラマソーム応答

    研究課題/研究課題番号:16K19638  2016年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    鳥居 ゆか, 川田 潤一, 村田 貴之, 川田 潤一, 村田 貴之

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    担当区分:研究代表者 

    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    ヒト白血球由来細胞株を用いてEpstein-Barrウイルス(EBV)感染時のインフラマソーム応答について検討した。通常EBVはヒトのB細胞に持続感染するが、細胞株を用いた実験では単球やT細胞にも感染することが示された。B細胞、T細胞由来の細胞株はEBV感染時にインフラマソーム応答の産物であるIL-1βの産生はみられなかったが、単球由来の細胞株ではIl-1βの産生がみられた。さらに細胞中の活性化カスパーゼ-1とパターン認識受容体の一つであるAIM2( Absent in Melanoma 2)の発現が増加しており、これら分子がEBV感染時の単球のインフラマソーム応答に関与していると考えられた。

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  3. 小児急性脳症の網羅的メタボローム・マイクロRNA解析を用いたバイオマーカー探索

    研究課題/研究課題番号:15J40217  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    鳥居 ゆか, 鳥居 ゆか

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    担当区分:その他 

    HHV-6感染が証明された症例をAESD(Acute encephalopathy with biphasic seizures and late reduced diffusion)タイプの脳症と診断された症例と、痙攣重積を起こしたが、その後意識回復良好で脳症に至らなかった症例の2群にわけ、それぞれ脳脊髄液エクソソーム中のマイクロRNAの発現プロファイルの比較解析を行った。髄液よりmiRCURY exosome isolatiom kitを用いてエクソソームを分離後、miRCURY RNA Isolation Kit Cell and Plantを用いてRNA抽出を行った。抽出したRNAからNEB Next Multiplex Small RNA Library Prep Set for Illuminaを用いてマイクロRNAのライブラリを作成した。作成したライブラリをMiseqでシーケンスを行った。脳症5例、対症5例の計10サンプルの解析を行い、出力したデータからマイクロRNA発現量を標準化して(RPAM: reads per annotated reads per million)比較解析をした。結果、10症例においてのべ292種のマイクロRNAが検出された。比較解析の結果、FDR(False Discovery Rate)<0.05を満たすのはmiR-381-3pのみであった。mir-381-3pは脳症群で有意に検出された。ターゲット遺伝子予測サイト(miRanda, Target Scan, mirDB)を用いて検索したところ、mir-381-3pの標的となると予測された遺伝子にはGRM8など神経伝達に関わる遺伝子もあり、病態との関連が考えられた。今回は10症例の検討のみであったが、PCRでの解析システムを確立して、より多くの症例を解析する必要があると思われた。

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担当経験のある科目 (本学以外) 1

  1. 先天感染症

    2022年2月 名古屋市立大学)

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    科目区分:学部専門科目  国名:日本国