Faculty Profiles - TAKAHASHI, Yoshiyuki

Papers - TAKAHASHI, Yoshiyuki

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A mutation in a proteasome subunit depletes its activities leading to excessive interferon signaling(和訳中)

川島希, 片岡伸介, 村松秀城, 大西秀典, 奥野友介, 今屋雅之, 山森彩子, 若松学, 濱田太立, 西川英里, 成田敦, 西尾信博, 小島勢二, 高橋義行

日本血液学会学術集会 Vol. 83回 page： OS1 - 5 2021.9

Relationship between plasma rabbit anti-thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia. International journal

Atsushi Narita, Hideki Muramatsu, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Kyogo Suzuki, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Asahito Hama, Hirohito Yamazaki, Shinji Nakao, Seiji Kojima, Yoshiyuki Takahashi

European journal of haematology Vol. 107 ( 2 ) page： 255 - 264 2021.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response. METHODS: From May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. A 1:1 block randomization was employed for 2.5 and 3.5 mg/kg doses of r-ATG. RESULTS: No significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups (63% vs. 58%, P = .894). Median r-ATG concentrations on days 14 and 28 after IST were 15.2 (0.0-97.7) and 1.8 (0.0-74.9 µg/mL), respectively. According to r-ATG concentration, response rates were significantly higher in the group with higher r-ATG concentration than in those with lower r-ATG concentration (day 14, 88% vs. 52%; P = .006 and day 28, 79% vs. 46%; P = .005). In multivariate analysis, higher r-ATG concentrations at day 28 were independent predictors of favorable response to IST at 6 months (odds ratio, 0.29; 95% confidence interval, 0.09-0.93; P = .037). CONCLUSIONS: The present data indicate that higher r-ATG concentration at day 28 resulted in improved IST response.

DOI： 10.1111/ejh.13644

Web of Science

PubMed

Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor Open Access

Shinsuke Kataoka, Nozomu Kawashima, Yusuke Okuno, Hideki Muramatsu, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, Norihiro Murakami, Rieko Taniguchi, Daisuke Ichikawa, Hironobu Kitazawa, Kyogo Suzuki, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Hidenori Yamamoto, Yoshie Fukasawa, Taichi Kato, Hiroyuki Yamamoto, Jun Natsume, Seiji Kojima, Ichizo Nishino, Takeshi Taketani, Hidenori Ohnishi, Yoshiyuki Takahashi

Journal of Allergy and Clinical Immunology Vol. 148 ( 2 ) page： 639 - 644 2021.8

Repetitive sleep starts: An important differential diagnosis of infantile spasms. International journal

Yuki Maki, Hiroyuki Kidokoro, Akihisa Okumura, Hiroyuki Yamamoto, Tomohiko Nakata, Tatsuya Fukasawa, Tetsuo Kubota, Masahiro Kawaguchi, Takeshi Suzuki, Masaharu Tanaka, Yu Okai, Yoko Sakaguchi, Atsuko Ohno, Tamiko Negoro, Yoshiyuki Takahashi, Jun Natsume

Epilepsy & behavior : E&B Vol. 121 ( Pt A ) page： 108075 - 108075 2021.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Repetitive sleep starts (RSS) are clusters of nonepileptic, spasm-like movements occurring during sleep onset. However, their characteristics have yet to be defined. We conducted a clinicoelectroencephalographic study of children with RSS to clarify their detailed characteristics. METHODS: To differentiate starts from epileptic spasms, we recruited children with brief "crescendo-decrescendo" muscle contractions that simultaneously involved the limbs and trunk without electroencephalogram changes, and that fulfilled the following criteria: (1) repeated occurrence (five or more) and (2) manifestation during sleep stage N1-N2. A total of nine children met these criteria. Their clinical information and video-electroencephalogram data were analyzed retrospectively. RESULTS: The background conditions observed at onset of RSS were perinatal hypoxic-ischemic encephalopathy (n = 4), West syndrome of unknown etiology (n = 1), and traumatic brain injury (n = 1). The age at onset of RSS, the number of starts in a given RSS cluster, the interval between starts, and the duration of surface electromyogram activity were between 3 and 46 months, 5 and 547, <1 and 60 s, and 0.3 and 5.4 s, respectively. None of the median value of these parameters differed between children with and without corticospinal tract injury. During the median follow-up period of 33 months, RSS disappeared spontaneously in five. CONCLUSION: This is the largest case series of RSS clarifying their clinicoelectroencephalographic characteristics reported to date. To avoid unnecessary antiepileptic therapies, clinicians should be aware of RSS and distinguish it from other disorders involving involuntary movements or seizures, especially epileptic spasms.

DOI： 10.1016/j.yebeh.2021.108075

Web of Science

PubMed

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy Open Access

Suzuki, T; Sato, Y; Kushida, Y; Tsuji, M; Wakao, S; Ueda, K; Imai, K; Iitani, Y; Shimizu, S; Hida, H; Temma, T; Saito, S; Iida, H; Mizuno, M; Takahashi, Y; Dezawa, M; Borlongan, CV; Hayakawa, M

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Vol. 41 ( 7 ) page： 1707 - 1720 2021.7

小児におけるcord colitis syndromeの臨床的・病理学的特徴

前村遼, 成田敦, 濱田太立, 鈴木喬悟, 西川英里, 川島希, 奥野友介, 西尾信博, 村松秀城, 伊藤雅文, 高橋義行

臨床血液 Vol. 62 ( 7 ) page： 863 - 863 2021.7

Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas. International journal Open Access

Daisuke Ichikawa, Kyoko Yamashita, Yusuke Okuno, Hideki Muramatsu, Norihiro Murakami, Kyogo Suzuki, Daiei Kojima, Shinsuke Kataoka, Motoharu Hamada, Rieko Taniguchi, Eri Nishikawa, Nozomu Kawashima, Atsushi Narita, Nobuhiro Nishio, Asahito Hama, Kenji Kasai, Seiji Mizuno, Yoshie Shimoyama, Masato Nakaguro, Hajime Okita, Seiji Kojima, Atsuko Nakazawa, Yoshiyuki Takahashi

NPJ genomic medicine Vol. 6 ( 1 ) page： 49 - 49 2021.6

Language：English Publishing type：Research paper (scientific journal)

Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.

DOI： 10.1038/s41525-021-00210-y

Open Access

Web of Science

PubMed

Age estimates from brain magnetic resonance images of children younger than two years of age using deep learning

Kawaguchi, M; Kidokoro, H; Ito, R; Shiraki, A; Suzuki, T; Maki, Y; Tanaka, M; Sakaguchi, Y; Yamamoto, H; Takahashi, Y; Naganawa, S; Natsume, J

MAGNETIC RESONANCE IMAGING Vol. 79 page： 38 - 44 2021.6

A Phase 2 Open-label, Single-arm, Multicenter Study of Ruxolitinib Added to Corticosteroids in Pediatric Subjects with Moderate/Severe Chronic Gvhd After Allogeneic Stem Cell Transplantation (REACH5)

Wall, D; Koh, K; Bhat, S; Takahashi, Y; Zhang, A; Rosko, C; Smith, Y; Stefanelli, T; Diaz-de-Heredia, C; Locatelli, F

BONE MARROW TRANSPLANTATION Vol. 56 ( SUPPL 1 ) page： 228 - 229 2021.6

診断および治療に難渋している、脳を含む全身性多発転移腫瘤を有する先天性肉腫の乳児

今屋雅之, 川島希, 山森彩子, 若松学, 吉田太郎, 三輪田俊介, 成田幸太郎, 北澤宏展, 谷口理恵子, 市川大輔, 濱田太立, 西川英里, 成田敦, 奥野友介, 村松秀城, 西尾信博, 小島勢二, 高橋義行, 中村栄男, 孝橋賢一, 大喜多肇

日本小児血液・がん学会雑誌 Vol. 58 ( 1 ) page： 60 - 60 2021.6

がん遺伝子パネル検査でGOPC-ROS1 fusionを認めた中枢神経胎児性腫瘍の0歳児症例

夏目敦至, 栗本路弘, 芝良樹, 青木恒介, 若林俊彦, 川島希, 谷口理恵子, 村松秀城, 高橋義行, 高野桂, 榊原綾子, 下山芳江, 中村栄男, 森田佐知, 安藤雄一, 平戸純子

日本小児血液・がん学会雑誌 Vol. 58 ( 1 ) page： 61 - 61 2021.6

Urinary biomarkers for monitoring treatment response in neuroblastoma patients.

Amano, H; Hinoki, A; Uchida, H; Yokota, K; Ishigaki, T; Sakairi, M; Abe, M; Takahashi, Y; Narita, A; Tainaka, T; Shirota, C; Sumida, W; Makita, S; Takimoto, A; Kano, Y; Yasui, A; Okamoto, M; Nakagawa, Y

JOURNAL OF CLINICAL ONCOLOGY Vol. 39 ( 15 ) 2021.5

Whole genome sequencing of 45 Japanese patients with intellectual disability Open Access

Abe-Hatano, C; Iida, A; Kosugi, S; Momozawa, Y; Terao, C; Ishikawa, K; Okubo, M; Hachiya, Y; Nishida, H; Nakamura, K; Miyata, R; Murakami, C; Takahashi, K; Hoshino, K; Sakamoto, H; Ohta, S; Kubota, M; Takeshita, E; Ishiyama, A; Nakagawa, E; Sasaki, M; Kato, M; Matsumoto, N; Kamatani, Y; Kubo, M; Takahashi, Y; Natsume, J; Inoue, K; Goto, YI

AMERICAN JOURNAL OF MEDICAL GENETICS PART A Vol. 185 ( 5 ) page： 1468 - 1480 2021.5

Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond–Blackfan anemia

Shun Koyamaishi, Takuya Kamio, Akie Kobayashi, Tomohiko Sato, Ko Kudo, Shinya Sasaki, Rika Kanezaki, Daiichiro Hasegawa, Hideki Muramatsu, Yoshiyuki Takahashi, Yoji Sasahara, Hidefumi Hiramatsu, Harumi Kakuda, Miyuki Tanaka, Masataka Ishimura, Masanori Nishi, Akira Ishiguro, Hiromasa Yabe, Takeo Sarashina, Masaki Yamamoto, Yuki Yuza, Nobuyuki Hyakuna, Kenichi Yoshida, Hitoshi Kanno, Shouichi Ohga, Akira Ohara, Seiji Kojima, Satoru Miyano, Seishi Ogawa, Tsutomu Toki, Kiminori Terui, Etsuro Ito

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1013 - 1020 2021.5

Language：English Publishing type：Research paper (scientific journal)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond–Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

DOI： 10.1038/s41409-020-01056-1

Web of Science

Scopus

PubMed

Correction: Reduced-intensity conditioning is effective for hematopoietic stem cell transplantation in young pediatric patients with Diamond-Blackfan anemia (Bone Marrow Transplantation, (2021), 56, 5, (1013-1020), 10.1038/s41409-020-01056-1) Open Access

Bone Marrow Transplantation Vol. 56 ( 5 ) page： 1218 - 1219 2021.5

Temporal dynamics of the plasma microbiome in recipients at early post-liver transplantation: a retrospective study. International journal Open Access

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

BMC microbiology Vol. 21 ( 1 ) page： 104 - 104 2021.4

Language：English Publishing type：Research paper (scientific journal)

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

Open Access

Web of Science

PubMed

Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B. International journal Open Access

Misa Miyake, Yoshiki Kawamura, Naoko Ishihara, Shigetaka Suzuki, Hiroki Miura, Yoko Sakaguchi, Masaharu Tanaka, Yoshiyuki Takahashi, Seiji Kojima, Hiroshi Toyama, Jun Natsume, Tetsushi Yoshikawa

Microorganisms Vol. 9 ( 4 ) 2021.4

Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippocampus was performed. Of the 107 patients that received HSCT at Nagoya University Hospital Between July 2008 and April 2014, 20 were eligible for volumetric analysis. Eight patients had HHV-6B infection, of whom two had encephalopathy at the time of HHV-6B infection. None of the 12 patients without HHV-6B infection had encephalopathy. The median ratio of the right hippocampal volume from before to after transplantation was 0.93 in patients with HHV-6B infection and 1.02 in without HHV-6B infection (p = 0.007). The median ratio of the left hippocampal volume ratio in patients with and without HHV-6B infection was 0.92 and 1.00, respectively (p = 0.003). Among the eight patients with HHV-6B infection, four had a marked reduction in hippocampal volume (volume ratio < 0.90). Only one of these patients had neurological symptoms at the time of HHV-6B infection. The reduction in the hippocampal volume ratio was higher in pediatric HSCT recipients with HHV-6B infection than those without viral infection. Neurological follow-up may be required for pediatric HSCT recipients with HHV-6B infection.

DOI： 10.3390/microorganisms9040776

Open Access

Web of Science

PubMed

Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation Open Access

Goto, T; Murata, M; Nishida, T; Terakura, S; Kamoshita, S; Ishikawa, Y; Ushijima, Y; Adachi, Y; Suzuki, S; Kato, K; Hirakawa, A; Nishiwaki, S; Nishio, N; Takahashi, Y; Kodera, Y; Matsushita, T; Kiyoi, H

STEM CELLS TRANSLATIONAL MEDICINE Vol. 10 ( 4 ) page： 542 - 553 2021.4

Phosphorylated proteome analysis of a novel germline ABL1 mutation causing an autosomal dominant syndrome with ventricular septal defect. International journal

Hidenori Yamamoto, Satoshi Hayano, Yusuke Okuno, Atsuto Onoda, Kohji Kato, Noriko Nagai, Yoshie Fukasawa, Shinji Saitoh, Yoshiyuki Takahashi, Taichi Kato

International journal of cardiology Vol. 326 page： 81 - 87 2021.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects. However, the molecular mechanisms of this syndrome remain unknown. In this study, we found a novel ABL1 mutation in a Japanese family with ventricular septal defect, finger contracture, skin abnormalities and failure to thrive, and the molecular mechanisms of these phenotypes were investigated. METHODS AND RESULTS: Whole-exome sequencing on several family members revealed a novel mutation (c.1522A > C, p.I508L) in the tyrosine kinase domain of ABL1, and complete co-segregation with clinical presentations was confirmed in all members. Wild-type and mutant ABL1 were transfected into human embryonic kidney 293 cells for functional analysis. Western blotting confirmed that tyrosine phosphorylation in STAT5, a substrate of ABL1, was enhanced, and the novel mutation was proved to be a gain-of-function mutation. Since this novel mutation in ABL1 enhances tyrosine kinase activity, phosphorylated proteome analysis was used to elucidate the molecular pathology. The proteome analysis showed that phosphorylation in proteins such as UFD1, AXIN1, ATRX, which may be involved in the phenotypes, was enhanced in the mutant group. CONCLUSIONS: The onset of congenital heart defects associated with this syndrome appears to involve a mechanism caused by UFD1 common to 22q.11.2 deletion syndrome. On the other hand, AXIN1 and ATRX may be important in elucidating the mechanisms of other phenotypes, such as finger contracture and failure to thrive. Verification of these hypotheses would lead to further understanding of the pathophysiology and the development of treatment methods.

DOI： 10.1016/j.ijcard.2020.10.032

Web of Science

PubMed

Initial treatment of seizures in children in an emergency department in rural Japan. International journal

Anna Shiraki, Masahiro Yasui, Hiroyuki Kidokoro, Shinji Kido, Hideo Ando, Yoshiyuki Takahashi, Jun Natsume

Brain & development Vol. 43 ( 2 ) page： 288 - 293 2021.2

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although the initial treatment of childhood seizures is important, treatment within an appropriate time window is often difficult in resource-limited areas. This study examined childhood seizure treatment in a rural area in Japan. METHODS: We retrospectively investigated children presenting to Nakatsugawa Municipal General Hospital emergency department between 2015 and 2018. From the hospital database, we identified children who were diagnosed with seizures, epilepsy, or acute infectious encephalitis/encephalopathy or were given benzodiazepines. We considered etiology, seizure duration, and treatment according to the specialties of the doctors providing initial care. RESULTS: We extracted 236 seizure events: 40 initially treated by pediatricians, 16 by a mobile doctor team, and 180 by other doctors. Twenty patients had continuous seizures for longer than 5 min on admission. Two were treated by pediatricians at presentation; it took 4 and 7 min after arrival to stop the seizures. Four were treated by a mobile team, and 14 by other doctors; the median response times were 11.5 (range 3-47) and 19 (range 5-60) min, respectively. All patients treated by pediatricians or mobile doctor teams received intravenous or intramuscular diazepam, whereas 50% of those treated by other doctors initially received diazepam suppositories. In three of the 20 events, establishing intravenous access was difficult. SIGNIFICANCE: In rural Japan, many children with seizures are initially treated by doctors other than pediatricians or emergency physicians, and they require a longer time to achieve seizure cessation. Non-intravenous benzodiazepine formulas, which have not yet been approved in Japan, would be helpful.

DOI： 10.1016/j.braindev.2020.08.004

Web of Science

PubMed

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Papers - TAKAHASHI, Yoshiyuki