Faculty Profiles - TAKAHASHI, Yoshiyuki

Papers - TAKAHASHI, Yoshiyuki

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Delayed recognition of childhood arterial ischemic stroke. Reviewed International journal

Ikumi Hori, Takeshi Tsuji, Misa Miyake, Kazuto Ueda, Erina Kataoka, Michio Suzuki, Satoru Kobayashi, Hirokazu Kurahashi, Yoshiyuki Takahashi, Akihisa Okumura, Tetsushi Yoshikawa, Shinji Saitoh, Jun Natsume

Pediatrics international : official journal of the Japan Pediatric Society Vol. 61 ( 9 ) page： 895 - 903 2019.9

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

BACKGROUND: Few population-based surveys of childhood arterial ischemic stroke (AIS) have been conducted in Asian countries. The aim of this study was to investigate the clinical features, time to diagnosis, and prognosis of childhood AIS in a population-based cohort in Japan. METHODS: Children aged 29 days-15 years 11 months old, residing in the Aichi Prefecture of Japan with radiologically confirmed AIS during 2010-2014, were identified retrospectively through questionnaires. We analyzed 40 children (23 boys, 17 girls; median age, 7 years 3 months), and collected time interval information of 26 patients. The time from clinical onset to first physician assessment and the time to AIS diagnosis were calculated. RESULTS: The most common presentation was paralysis or paresis in 27 patients (71%). No underlying disorders or possible trigger factors were identified in 14 patients (35%). The median time from symptom onset to first physician assessment was 2.9 h. The median time from symptom onset to the confirmed AIS diagnosis was 27.0 h. The diagnosis of AIS was made in the first 6 h after onset of symptoms in 27% of patients for whom the time was available. Radiological diagnosis took longer than 24 h in 54% of these patients. CONCLUSIONS: Long in-hospital delays exist in the diagnosis of AIS in children, likely due to lack of awareness of stroke by doctors. Further efforts to increase public and physician awareness of childhood stroke are needed to ensure early diagnosis and treatment.

DOI： 10.1111/ped.13966

Web of Science

PubMed

Risk factors for absence of catch-up growth in small for gestational age very low-birthweight infants. Reviewed International journal

Sakiko Arai, Yoshiaki Sato, Hideki Muramatsu, Hidenori Yamamoto, Fumiko Aoki, Yu Okai, Shinsuke Kataoka, Yu Hanada, Motoharu Hamada, Yoshihito Morimoto, Seiji Kojima, Jun Natsume, Yoshiyuki Takahashi

Pediatrics international : official journal of the Japan Pediatric Society Vol. 61 ( 9 ) page： 889 - 894 2019.9

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

BACKGROUND: Many small for gestational age (SGA) infants have catch-up growth during the first 2 years of life, but approximately 10% have no catch-up growth, and short stature continues into adulthood. Identification of risk factors for absence of catch-up growth at an early age may be useful for earlier diagnosis and earlier treatment. METHODS: This was a retrospective multicenter study. The subjects were SGA infants with very low-birthweight (VLBW), who were followed up until the age of 3 years. The risk factors for absence of catch-up growth were identified on statistical analysis. RESULTS: Of the 217 SGA infants in this study, 181 were in the catch-up group and 36 were in the no catch-up group. The catch-up rate was 83%. On multivariate analysis adjusted for gestational age, birthweight, birth height, and birth head circumference, multipara, Z and ΔZ scores of length at 12 months of corrected age, and the Z score of height at 24 months of corrected age were risk factors for lack of catch-up at 3 years. CONCLUSIONS: The length Z and ΔZ scores at 12 months of corrected age may be useful for an earlier diagnosis and earlier initiation of growth hormone treatment in VLBW infants.

DOI： 10.1111/ped.13939

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PubMed

再発難治急性リンパ性白血病に対する新規治療戦略次世代シークエンサーの臨床応用と遺伝子導入T細胞療法

高橋義行

日本小児血液・がん学会雑誌 Vol. 56 ( 2 ) page： 244 - 244 2019.9

がんゲノム解析の新しい流れ(全ゲノム解析、クラウド解析、全がん解析、ロングリード解析などの新規技術) 若年性骨髄単球性白血病における全ゲノム解析(Frontiers in cancer genomics Whole-genome mutational analysis of juvenile myelomonocytic leukemia)

奥野友介, 村松秀城, 村上典寛, 川島希, 若松学, 北澤宏展, 荻朋男, 高橋義行

日本癌学会総会記事 Vol. 78回 page： S23 - 2 2019.9

SMARCA4不活化により発症し治療抵抗性を示した胸部腫瘍の1例

市川大輔, 村松秀城, 奥野友介, 若松学, 三輪田俊介, 成田幸太郎, 北澤宏展, 濱田太立, 片岡伸介, 村上典寛, 谷口理恵子, 鈴木喬悟, 西川英里, 西尾信博, 川島希, 成田敦, 小島勢二, 高橋義行, 中黒匡人, 中村栄男, 中澤温子

日本小児血液・がん学会雑誌 Vol. 56 ( 2 ) page： 246 - 246 2019.9

CAR-T細胞の臨床応用急性リンパ性白血病に対する非ウイルスベクター法を用いたCAR-T細胞療法の開発(CAR-T in Clinics Development of CAR-T cell therapy for acute lymphoblastic leukemia using non-virus vector system)

高橋義行

日本癌学会総会記事 Vol. 78回 page： S5 - 2 2019.9

Constitutive activation of mTORC1 signaling induced by biallelic loss-of-function mutations in SZT2 underlies a discernible neurodevelopmental disease. Reviewed International journal Open Access

Yuji Nakamura, Kohji Kato, Naomi Tsuchida, Naomichi Matsumoto, Yoshiyuki Takahashi, Shinji Saitoh

PloS one Vol. 14 ( 8 ) page： e0221482 2019.8

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

There have been increasing number of reports of SZT2-related neurological diseases, the main symptoms of which are epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum. SZT2 functions as a regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling in cultured human cell lines and mouse tissues. However, it remains to be determined whether mutations in SZT2 in human patients alter mTORC1 signaling. In this study, we aimed to investigate the functional consequence of biallelic SZT2 variants in Epstein-Barr virus-induced lymphoblastoid cell lines (LCLs) established from two patients with a typical SZT2-related neurodevelopmental disease. Increased phosphorylation of S6 kinase and S6 was identified in patient-derived cell lines under amino acid-starved condition, suggestive of constitutive hyperactivation of mTORC1 signaling. This result was validated by constitutive lysosomal localization of mTOR in patients' LCLs. Furthermore, patients' LCLs display an excessive response to slight amino acid stimulation. Our data suggest the loss-of-function nature of SZT2 mutations in the patients, and consequent hyperactivation of mTORC1 signaling in response to both amino acid starvation and stimulation in their LCLs. By these functional analyses, the pathogenicity of newly identified SZT2 variants can be determined, allowing for more detailed characterization of genotype-phenotype correlations.

DOI： 10.1371/journal.pone.0221482

Open Access

Web of Science

PubMed

Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning. Reviewed International journal Open Access

Katsutsugu Umeda, Hiromasa Yabe, Koji Kato, Kohsuke Imai, Masao Kobayashi, Yoshiyuki Takahashi, Nao Yoshida, Maho Sato, Yoji Sasahara, Keisuke Kato, Souichi Adachi, Yuhki Koga, Keiko Okada, Masami Inoue, Yoshiko Hashii, Yoshiko Atsuta, Tomohiro Morio

Bone marrow transplantation Vol. 54 ( 8 ) page： 1227 - 1236 2019.8

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

Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1-6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35-0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32-0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.

DOI： 10.1038/s41409-018-0418-8

Web of Science

PubMed

愛知県におけるチャイルド・デス・レビューの試み

沼口敦, 高橋義行, 夏目淳, 伊藤嘉規, 齋藤伸治, 吉川哲史, 奥村彰久

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1313 - 1313 2019.8

小児重症呼吸不全患者の気管支肺胞洗浄液を用いた次世代シークエンス法による病原微生物の網羅的検出

武内俊, 川田潤一, 堀場千尋, 奥村俊彦, 鈴木高子, 鳥居ゆか, 奥野友介, 高橋義行, 伊藤嘉規, 河邉慎司, 池山貴也

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1336 - 1336 2019.8

先天性嚢胞性肺疾患との鑑別に苦慮した巨大縦隔気腫の2例

本部和也, 脇田浩正, 上田一仁, 田中亮, 三浦良介, 呉尚治, 浅田英之, 北瀬悠磨, 鈴木俊彦, 兵藤玲奈, 見松はるか, 伊藤美春, 齊藤明子, 村松友佳子, 佐藤義朗, 早川昌弘, 高橋義行

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1312 - 1312 2019.8

ステロイド減量に伴い再発を繰り返した抗MOG抗体陽性急性散在性脳脊髄炎(ADEM)の1例

隈井すみれ, 山本啓之, 川口将宏, 牧祐輝, 田中雅大, 岡井佑, 坂口陽子, 中田智彦, 城所博之, 高橋義行, 夏目淳, 濱口直子, 柴田元博, 金子仁彦, 高橋利幸

日本小児科学会雑誌 Vol. 123 ( 8 ) page： 1310 - 1310 2019.8

テクノロジーの進展は検査医学をどう変えるか急性リンパ性白血病に対する次世代シークエンサーを用いた遺伝子診断およびキメラ抗原受容体遺伝子改変T(CAR-T)細胞療法

高橋義行

臨床病理 Vol. 67 ( 8 ) page： 884 - 884 2019.8

CF290 for pancolonic chromoendoscopy improved sessile serrated polyp detection and procedure time: a propensity score-matching study. Reviewed

Toyoshima O, Yoshida S, Nishizawa T, Yamakawa T, Sakitani K, Hata K, Takahashi Y, Fujishiro M, Watanabe H, Koike K

Endoscopy international open Vol. 7 ( 8 ) page： E987 - E993 2019.8

Whole abdominopelvic intensity-modulated radiation therapy for peritoneal disseminated rhabdomyosarcoma with three-year follow-up: a case report. Reviewed International journal Open Access

Mariko Kawamura, Kuniyasu Okudaira, Yoshiyuki Itoh, Takeshi Kamomae, Eri Nishikawa, Hideki Muramatsu, Yoshiyuki Takahashi, Kazuki Yokota, Shinji Naganawa

Radiation oncology (London, England) Vol. 14 ( 1 ) page： 127 - 127 2019.7

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

BACKGROUND: The role of local radiotherapy in the treatment of metastatic rhabdomyosarcoma is important. However, with peritoneal dissemination, the application of local therapy is challenging. Although there are few reports addressing the efficacy of the whole abdominopelvic irradiation to peritoneal disseminated rhabdomyosarcoma patients, no precise curse of treatment nor the follow up result is explained in paper nor in the text. CASE PRESENTATION: Six years old rhabdomyosarcoma boy with peritoneal dissemination was treated at our facility under COG D9803 protocol (vincristine, dactinomycin, and cyclophosphamide (VAC)). He underwent tumor resection on the 14th week according to the protocol. During surgery, the 2-cm residual tumor was completely resected, but in the pelvis, numerous nodules that were suspected as peritoneal disseminated tumors were observed. We administered 30 Gy/20fr whole abdominopelvic radiotherapy using volumetric modulated arc therapy (VMAT) technique and a 6 Gy sequential boost to pelvis after the surgery and completed the protocol treatment. During the course of treatment, the patient experienced G4 hematological toxicity and received multiple transfusions, particularly after whole abdominopelvic irradiation. He has achieved complete remission and is alive without evidence of recurrence and severe late adverse effect for 3 years. In terms of growth, his height and weight are within the average values for Japanese boys at the same age. CONCLUSION: By using the VMAT technique, a patient with peritoneal disseminated rhabdomyosarcoma can be treated, and a dose of 30 Gy to the whole abdominopelvis with concurrent chemotherapy may be tolerable.

DOI： 10.1186/s13014-019-1333-x

Open Access

Web of Science

PubMed

Comparison of Clinical Characteristics of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Young Children. Reviewed Open Access

Akinobu Taniguchi, Jun-Ichi Kawada, Kiyotaka Go, Naozumi Fujishiro, Yosuke Hosokawa, Yuki Maki, Yuichiro Sugiyama, Michio Suzuki, Takeshi Tsuji, Shin Hoshino, Hideki Muramatsu, Hiroyuki Kidokoro, Fumie Kinoshita, Akihiro Hirakawa, Yoshiyuki Takahashi, Yoshiaki Sato, Jun Natsume

Japanese journal of infectious diseases Vol. 72 ( 4 ) page： 237 - 242 2019.7

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

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory tract infection in children, and clinical manifestations of these virus infections are considered similar. To investigate the differences in clinical characteristics between HMPV and RSV infections in young children, we prospectively enrolled children ＜ 3 years old who required hospitalization with acute respiratory tract infection due to HMPV or RSV at 10 hospitals in Japan. We enrolled 48 children with HMPV infection and 141 with RSV infection. Patients with HMPV infection were older than those with RSV infection. High-grade fever was more frequently observed in patients with HMPV infection, whereas no significant differences in respiratory symptoms were apparent. Abnormal serum lactate dehydrogenase values and consolidation shadows on chest X-ray were more frequently observed in patients with HMPV infection. During hospitalization, nasal mucus suction was more frequently required in patients with RSV infection. On the other hand, β2-adrenergic agonists, corticosteroids, and leukotriene receptor antagonists were more frequently used in patients with HMPV infection. These findings suggest that HMPV and RSV infections show similar respiratory symptoms, but HMPV infection is more likely to lead to the development of pneumonia, at least among hospitalized young children.

DOI： 10.7883/yoken.JJID.2018.480

Open Access

Web of Science

PubMed

Effects of HLA mismatch on cytomegalovirus reactivation in cord blood transplantation Open Access

Yokoyama, H; Kanda, J; Kato, S; Kondo, E; Maeda, Y; Saji, H; Takahashi, S; Onizuka, M; Onishi, Y; Ozawa, Y; Kanamori, H; Ishikawa, J; Ohno, Y; Ichinohe, T; Takanashi, M; Kato, K; Atsuta, Y; Kanda, Y; Ikegame, K; Utsunomiya, A; Kawase, T; Kim, SW; Kuwatsuka, Y; Kobayashi, T; Takatsuka, Y; Takahashi, Y; Tanaka, J; Tamaki, H; Tsuji, M; Nishida, T; Masuko, M; Matsuno, R; Murata, M; Morishima, S; Morishima, Y; Yokoyama, H; Wake, A; Watanabe, N; Ashida, T; Hoshino, T; Yabe, T; Sakamoto, K; Fuji, S; Miyamura, K; Arima, N; Kondo, E; Yoshimitsu, M; Kawamura, K; Kawata, T; Kishimoto, K; Tatara, R; Hagino, T; Fujiwara, SI; Shimomura, Y; Sakaguchi, H; Hirabayashi, S; Ishii, H; Onda, Y; Kato, I; Kawajiri, A; Shindo, T; Tokunaga, M; Nonami, A; Muranushi, H; Yoshinaga, N; Kawashima, N; Shiratori, S; Tada, Y; Tanoue, SU; Hirayama, M; Fukunaga, K; Ohbiki, M

BONE MARROW TRANSPLANTATION Vol. 54 ( 7 ) page： 1004 - 1012 2019.7

Relationship between plasma rabbit anti-thymocyte globulin level and response to immunosuppressive therapy in patients with severe aplastic anemia: Results of a multicenter, prospective, randomized study

Narita, A; Muramatsu, H; Xu, YY; Nishikawa, E; Kawashima, N; Okuno, Y; Nishio, N; Hama, A; Yamazaki, H; Nakao, S; Kojima, S; Takahashi, Y

BONE MARROW TRANSPLANTATION Vol. 54 page： 29 - 29 2019.7

Narita Atsushi, Muramatsu Hideki, Xu Yinyan, Nishikawa Eri, Kawashima Nozomu, Okuno Yusuke, Nishio Nobuhiro, Hama Asahito, Yamazaki Hirohito, Nakao Shinji, Kojima Seiji, Takahashi Yoshiyuki

BONE MARROW TRANSPLANTATION Vol. 54 page： 29-29 2019.7

MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. Reviewed International journal

Kohji Kato, Fuyuki Miya, Nanako Hamada, Yutaka Negishi, Yoko Narumi-Kishimoto, Hiroshi Ozawa, Hidenori Ito, Ikumi Hori, Ayako Hattori, Nobuhiko Okamoto, Mitsuhiro Kato, Tatsuhiko Tsunoda, Yonehiro Kanemura, Kenjiro Kosaki, Yoshiyuki Takahashi, Koh-Ichi Nagata, Shinji Saitoh

Journal of medical genetics Vol. 56 ( 6 ) page： 388 - 395 2019.6

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

BACKGROUND: In this study, we aimed to identify the gene abnormality responsible for pathogenicity in an individual with an undiagnosed neurodevelopmental disorder with megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly and neuroblastoma. We then explored the underlying molecular mechanism. METHODS: Trio-based, whole-exome sequencing was performed to identify disease-causing gene mutation. Biochemical and cell biological analyses were carried out to elucidate the pathophysiological significance of the identified gene mutation. RESULTS: We identified a heterozygous missense mutation (c.173C>T; p.Thr58Met) in the MYCN gene, at the Thr58 phosphorylation site essential for ubiquitination and subsequent MYCN degradation. The mutant MYCN (MYCN-T58M) was non-phosphorylatable at Thr58 and subsequently accumulated in cells and appeared to induce CCND1 and CCND2 expression in neuronal progenitor and stem cells in vitro. Overexpression of Mycn mimicking the p.Thr58Met mutation also promoted neuronal cell proliferation, and affected neuronal cell migration during corticogenesis in mouse embryos. CONCLUSIONS: We identified a de novo c.173C>T mutation in MYCN which leads to stabilisation and accumulation of the MYCN protein, leading to prolonged CCND1 and CCND2 expression. This may promote neurogenesis in the developing cerebral cortex, leading to megalencephaly. While loss-of-function mutations in MYCN are known to cause Feingold syndrome, this is the first report of a germline gain-of-function mutation in MYCN identified in a patient with a novel megalencephaly syndrome similar to, but distinct from, CCND2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. The data obtained here provide new insight into the critical role of MYCN in brain development, as well as the consequences of MYCN defects.

DOI： 10.1136/jmedgenet-2018-105487

Web of Science

PubMed

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Papers - TAKAHASHI, Yoshiyuki