Faculty Profiles - TAKAHASHI, Yoshiyuki

Papers - TAKAHASHI, Yoshiyuki

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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

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： 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

Combination of tumor necrosis factor-α and epidermal growth factor induces the adrenergic-to-mesenchymal transdifferentiation in SH-SY5Y neuroblastoma cells. International journal Open Access

Yue Huang, Shoma Tsubota, Nobuhiro Nishio, Yoshiyuki Takahashi, Kenji Kadomatsu

Cancer science Vol. 112 ( 2 ) page： 715 - 724 2021.2

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

Neuroblastoma, a type of cancer that is common in children, is composed of two genetically clonal but epigenetically distinct cell types: mesenchymal (MES) and adrenergic (ADRN) types, controlled by super-enhancer-associated lineage-specific transcription factor networks. Mesenchymal-type cells are more migratory, resistant to chemotherapy, and prevalent in relapse tumors. Importantly, both cell types spontaneously transdifferentiate into one another, and this interconversion can be induced by genetic manipulations. However, the mechanisms of their spontaneous transdifferentiation and extracellular factors inducing this phenomenon have not yet been elucidated. Using a unique approach involving gene set enrichment analysis, we selected six ADRN and 10 MES candidate factors, possibly inducing ADRN and MES phenotypes, respectively. Treatment with a combination of 10 MES factors clearly induced the MES gene expression profile in ADRN-type SH-SY5Y neuroblastoma cells. Considering the effects on gene expression profile, migration ability, and chemoresistance, a combination of tumor necrosis factor alpha (TNF-α) and epidermal growth factor (EGF) was sufficient to synergistically induce the ADRN-to-MES transdifferentiation in SH-SY5Y cells. In addition, human neuroblastoma cohort analysis revealed that the expression of TNF and EGF receptors was strongly associated with MES gene expression signatures, supporting their important roles in transdifferentiation in vivo. Collectively, we propose a mechanism of neuroblastoma transdifferentiation induced by extracellular growth factors, which can be controlled in clinical situations, providing a new therapeutic possibility.

DOI： 10.1111/cas.14760

Open Access

Web of Science

PubMed

Shuffling babies and autism spectrum disorder. International journal

Yu Okai, Tomohiko Nakata, Kiyokuni Miura, Atsuko Ohno, Rie Wakako, Osamu Takahashi, Yuki Maki, Masaharu Tanaka, Yoko Sakaguchi, Yuji Ito, Hiroyuki Yamamoto, Hiroyuki Kidokoro, Yoshiyuki Takahashi, Jun Natsume

Brain & development Vol. 43 ( 2 ) page： 181 - 185 2021.2

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

BACKGROUND AND PURPOSE: Bottom shuffling is a locomotion strategy that precedes independent walking in some infants. Shuffling babies are generally considered to have favorable outcomes. The aim of the present study was to reveal clinical features and neurodevelopmental outcomes of shuffling babies who visited a child developmental center. METHODS: We studied 48 shuffling babies who visited Toyota Municipal Child Development Center from April 2007 to March 2015. We excluded patients with cerebral palsy, Down syndrome, or congenital disorders. In 2018, we retrospectively reviewed the clinical charts of the enrolled children. We investigated family history, neurological findings, and the developmental outcome during the follow-up period. RESULTS: During the follow-up period, 20 children (42%) were diagnosed with ASD. Gross motor development in infancy was not different between infants with and without ASD. The rate of poor eye contact at the first visit and a delay in the first word speech were significantly higher in infants with ASD than in infants without ASD. A family history of bottom shuffling was significantly less frequent in infants with ASD (10%) than in those without (39%). CONCLUSION: Some of bottom shufflers may represent ASD during follow-up. Paying attention to social and cognitive functions in shuffling babies is important.

DOI： 10.1016/j.braindev.2020.08.007

Web of Science

PubMed

術前診断にて良性腫瘍と考えられたが全摘出できなかった腰髄腫瘍の2歳男児

吉田太郎, 村松秀城, 今屋雅之, 山森彩子, 若松学, 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, 川島希, 成田敦, 西尾信博, 小島勢二, 高橋義行, 田中智史, 安藤圭, 小林和克, 今釜史郎, 中黒匡人, 平戸純子

日本小児血液・がん学会雑誌 Vol. 57 ( 5 ) page： 409 - 410 2021.2

胎児発育不全に伴う脳発達異常の早期診断法確立に向けたバイオマーカーの探索

小野田淳人, 北瀬悠磨, 辻雅弘, 上田一仁, 高橋義行, 早川昌弘, 佐藤義朗

日本小児科学会雑誌 Vol. 125 ( 2 ) page： 216 - 216 2021.2

化学療法による治療介入を行った生後2ヵ月未満発症の神経芽腫4S

今屋雅之, 西川英里, 吉田太郎, 山森彩子, 若松学, 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, 川島希, 成田敦, 村松秀城, 西尾信博, 小島勢二, 高橋義行

日本小児血液・がん学会雑誌 Vol. 57 ( 5 ) page： 411 - 411 2021.2

Long-term outcome in patients with Fanconi anemia who received hematopoietic stem cell transplantation: a retrospective nationwide analysis.

Miharu Yabe, Tomohiro Morio, Ken Tabuchi, Daisuke Tomizawa, Daiichiro Hasegawa, Hiroyuki Ishida, Nao Yoshida, Takashi Koike, Yoshiyuki Takahashi, Katsuyoshi Koh, Yasuhiro Okamoto, Hideki Sano, Keisuke Kato, Yoshinobu Kanda, Hiroaki Goto, Junko Takita, Takako Miyamura, Maiko Noguchi, Koji Kato, Yoshiko Hashii, Yoshiko Astuta, Hiromasa Yabe

International journal of hematology Vol. 113 ( 1 ) page： 134 - 144 2021.1

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

We retrospectively analyzed nationwide records of 163 Fanconi anemia (FA) patients [aplastic anemia (AA), n = 118; myelodysplastic syndrome (MDS), n = 30; acute leukemia, n = 15] who underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 1987 and 2015 in Japan. An alternative donor was used in 119 (73%) patients, and 160 (98%) patients received a non-T-cell-depleted graft. With an 8.7-year median follow-up, 5-year overall survival (OS) was 81%. The 5-year OS was significantly higher in AA patients than in MDS and acute leukemia patients (89%, 71%, and 44%, respectively). In the MDS/leukemia group, factors associated with poor outcome in univariate analysis were older age at HSCT (≥ 18 years), conditioning regimen without anti-thymocyte or lymphocyte globulin, and grade II-IV acute graft-versus-host disease. After 1 year, of 137 survivors, 15 developed subsequent malignancies, of whom 12 were diagnosed with head and neck (HN)/esophageal cancer. An irradiation regimen and older age were associated with the risk of HN/esophageal cancer. Five of seven deaths were attributed to subsequent malignancies more than 5 years after HSCT. On the basis of the risk factors for HSCT in MDS/leukemia patients and subsequent malignancies, a more effective HSCT approach is required.

DOI： 10.1007/s12185-020-02991-x

Web of Science

PubMed

Detection of subclonal SETBP1 and JAK3 mutations in juvenile myelomonocytic leukemia using droplet digital PCR. Reviewed International journal

Manabu Wakamatsu, Yusuke Okuno, Norihiro Murakami, Shunsuke Miwata, Hironobu Kitazawa, Kotaro Narita, Shinsuke Kataoka, Daisuke Ichikawa, Motoharu Hamada, Rieko Taniguchi, Kyogo Suzuki, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Hideki Muramatsu, Yoshiyuki Takahashi

Leukemia Vol. 35 ( 1 ) page： 259 - 263 2021.1

A Breast-Fed Baby with Low KREC in TREC/KREC Newborn Screening Whose Mother Received Azathioprine Treatment

Manabu Wakamatsu, Hideki Muramatsu, Daiei Kojima, Yusuke Okuno, Yoshimi Sakai, Yoko Nakajima, Tetsuya Ito, Nozomu Kawashima, Atsushi Narita, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Allogeneic Stem Cell Transplantation from Alternative Donors for Children with Aplastic Anemia

Atsushi Narita, Hideki Muramatsu, Masayuki Imaya, Ayako Yamamori, Taro Yoshida, Manabu Wakamatsu, Shunsuke Miwata, Koutaro Narita, Hironobu Kitazawa, Rieko Taniguchi, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 215 - 216 2020.12

Allogeneic Hematopoietic Cell Transplantation in First Remission in Children with AML: A Comparison of RIC and MAC

Asahito Hama, Daiki Yamashita, Daichi Sajiki, Hironobu Kitazawa, Hirotoshi Sakaguchi, Nao Yoshida, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Clinical Features of Cord Colitis Syndrome in Children

Ryo Maemura, Atsushi Narita, Daisuke Ichikawa, Motoharu Hamada, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Biomarkers for Distinguishing between acute GVHD and HHV-6B-Associated Skin Rash after Hematopoietic Stem Cell Transplantation

Miura, H; Kudo, K; Tanaka, M; Takahashi, Y; Kojima, S; Yoshikawa, T

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

INFANTILE HEMISPHERIC BRAIN TUMOR WITH A GOPC-ROS1 FUSION GENE: A CASE REPORT Open Access

Rieko Taniguchi, Atsushi Natsume, Nozomu Kawashima, Shinji Tanioka, Hideki Muramatsu, Motoharu Hamada, Daisuke Ichikawa, Masayuki Imaya, Kotaro Narita, Michihiro Kurimoto, Yoshiki Shiba, Kosuke Aoki, Fumiharu Ohka, Junko Hirato, Toshihiko Wakabayashi, Yoshiyuki Takahashi

NEURO-ONCOLOGY Vol. 22 page： 377 - 377 2020.12

Development of Donor-Derived T cell EBV-LPD with Identical EBV Genome after Allogeneic CBT in the NK Cell-Type CAEBV Patient

Masayuki Imaya, Yusuke Okuno, Nozomu Kawashima, Manabu Wakamatsu, Hideki Muramatsu, Nobuhiro Nishio, Akihisa Sawada, Junichi Kawada, Yoshinori Ito, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

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Papers - TAKAHASHI, Yoshiyuki