Faculty Profiles - TAKAHASHI, Yoshiyuki

Papers - TAKAHASHI, Yoshiyuki

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Hematopoietic Stem Cell Transplantation for Inborn Errors of Immunity in Japan: Overview of a Nationwide Retrospective Analysis

Miyamoto, S; Yanagimachi, M; Umeda, K; Iguchi, A; Sasahara, Y; Takada, H; Yamada, M; Ishimura, M; Koike, T; Yasui, M; Takahashi, Y; Kawaguchi, H; Kajiwara, M; Inoue, M; Kato, K; Hashii, Y; Atsuta, Y; Yabe, H; Imai, K; Morio, T

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 102 - 103 2020.12

Favorable Prognosis of Patients with Intermediate-Risk Neuroblastoma Having Residual Tumor after Treatment

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

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Effect of Azacitidine in a Child with Fanconi Anemia and Myelodysplastic Syndrome Harboring Monosomy 7

Nozomu Kawashima, Masafumi Ito, Kotaro Narita, Daisuke Ichikawa, Eri Nishikawa, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome Open Access

Yasuyoshi Oka, Motoharu Hamada, Yuka Nakazawa, Hideki Muramatsu, Yusuke Okuno, Koichiro Higasa, Mayuko Shimada, Honoka Takeshima, Katsuhiro Hanada, Taichi Hirano, Toshiro Kawakita, Hirotoshi Sakaguchi, Takuya Ichimura, Shuichi Ozono, Kotaro Yuge, Yoriko Watanabe, Yuko Kotani, Mutsumi Yamane, Yumiko Kasugai, Miyako Tanaka, Takayoshi Suganami, Shinichiro Nakada, Norisato Mitsutake, Yuichiro Hara, Kohji Kato, Seiji Mizuno, Noriko Miyake, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Seiji Kito, Keiichi Isoyama, Masafumi Onodera, Hideo Kaneko, Naomichi Matsumoto, Fumihiko Matsuda, Keitaro Matsuo, Yoshiyuki Takahashi, Tomoji Mashimo, Seiji Kojima, Tomoo Ogi

Science Advances Vol. 6 ( 51 ) page： eabd7197 - eabd7197 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：American Association for the Advancement of Science (AAAS)

Rs671 in the aldehyde dehydrogenase 2 gene (<italic>ALDH2</italic>) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (<italic>ADH5FDH</italic>), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, <italic>Adh5−/−Aldh2</italic>E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.

DOI： 10.1126/sciadv.abd7197

Open Access

Web of Science

PubMed

Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency in Japan: A Nationwide Retrospective Analysis

Miyamoto, S; Yanagimachi, M; Umeda, K; Iguchi, A; Sasahara, Y; Takada, H; Takahashi, Y; Kajiwara, M; Inoue, M; Kato, K; Hashii, Y; Atsuta, Y; Yabe, H; Imai, K; Morio, T

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 443 - 443 2020.12

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

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

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Microsatellite Instability-High is Rare Events in Refractory Pediatric Solid Tumors Open Access

Yoshida, T; Muramatsu, H; Wakamatsu, M; Taniguchi, R; Ichikawa, D; Nakaguro, M; Natsume, A; Takahashi, Y

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Reduced Intensity Conditioning is Effective for Hematopoietic stem Cell Transplantation in Patients with Diamond-Blackfan ANEMIA

Koyamaishi, S; Kamio, T; Kobayashi, A; Sato, T; Kudo, K; Sasaki, S; Kanezaki, R; Hasegawa, D; Muramatsu, H; Takahashi, Y; Sasahara, Y; Hiramatsu, H; Kakuda, H; Tanaka, M; Ishimura, M; Nishi, M; Ishiguro, A; Yabe, H; Yoshida, K; Kanno, H; Ohga, S; Ohara, A; Kojima, S; Miyano, S; Ogawa, S; Toki, T; Terui, K; Ito, E

BONE MARROW TRANSPLANTATION Vol. 55 ( SUPPL 1 ) page： 36 - 37 2020.12

Strategy of Stem Cell Transplantation at 1st Molecular CR for Pediatric Acute Lymphoblastic Leukemia with MEF2D-BCL9 Fusion

Motoharu Hamada, Masayuki Imaya, Yusuke Okuno, Daisuke Ichikawa, Nozomu Kawashima, Atsushi Narita, Eri Nishikawa, Hideki Muramatsu, Nobuhiro Nishio, Yoshiyuki Takahashi

PEDIATRIC BLOOD & CANCER Vol. 67 2020.12

Myelodysplastic syndromes in a pediatric patient with Cri du Chat syndrome with a ring chromosome 5. Reviewed

Akifumi Nozawa, Michio Ozeki, Shiho Yasue, Saori Endo, Tomonori Kadowaki, Hidenori Ohnishi, Hideki Muramatsu, Asahito Hama, Yoshiyuki Takahashi, Seiji Kojima, Toshiyuki Fukao

International journal of hematology Vol. 112 ( 5 ) page： 728 - 733 2020.11

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

Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based on the morphological findings of bone marrow, the patient was diagnosed with refractory cytopenia with multilineage dysplasia. The risk group was classified as intermediate-1 in the International Prognostic Scoring System (IPSS), and low in the revised IPSS. Assessment by microarray comparative genomic hybridization (CGH) identified the breakpoints of ring chromosome 5 as 46,XX,r(5)(p14.3q35.3). This revealed that the 5q terminal deletion did not include the common deleted region of MDS with del(5q). Treatment with azacitidine was initiated to control disease progression and improve quality of life. At baseline, the patient had a mean transfusion requirement of 3 units/month, which decreased to 2 units/month after six cycles of azacitidine and to 1 unit/month after 10 cycles of azacitidine. Cytopenia observed in the presented case seemed irrelevant to ring chromosome 5 which is the causative cytogenetic abnormality of CdCS, and further analyses may be needed to clarify the pathogenesis.

DOI： 10.1007/s12185-020-02909-7

Web of Science

PubMed

Risk factors for secondary poor graft function after bone marrow transplantation in children with acquired aplastic anemia Reviewed International journal

Asahito Hama, Hideki Muramatsu, Atsushi Narita, Eri Nishikawa, Nozomu Kawashima, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi

Pediatric transplantation Vol. 24 ( 7 ) page： e13828 2020.11

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

In patients with acquired AA, PGF is a major cause of cytopenia after hematopoietic stem cell transplantation. An increased incidence of PGF, especially sPGF, has been noted after the introduction of the FLU/CY regimen in children with acquired AA. To clarify the risk factors for sPGF, the clinical data of 49 patients (median age, 11 years; range, 1-19 years) with AA who received allogeneic BMT at Nagoya University Hospital from 1997 to 2016 were analyzed. Out of the 49 patients, 7 developed sPGF, and the 5-year CI was 0.15 (95% CI, 0.04-0.25). Five received the FLU/CY regimen, and the 5-year CI of sPGF was significantly higher in patients who received the regimen (0.36; 95% CI, 0.12-0.62) than in those who were conditioned with the non-FLU/CY regimen (0.06; 95% CI, 0.01-0.17; P =.01). The multivariate analysis confirmed that the FLU/CY regimen (hazard ratio, 6.12; 95% CI, 1.16-32.4; P =.03) was a significant risk factor for sPGF. sPGF improved spontaneously without stem cell boost infusions in 5 patients, ranging from 460 to 3539 days after BMT. The 10-year CI of the spontaneous trilineage recovery was 0.83 (95% CI, 0.00-0.97), and all 7 patients are alive. The FLU/CY regimen was identified as a risk factor for the sPGF development in patients with AA. The establishment of the optimal conditioning regimens for children with AA is warranted.

DOI： 10.1111/petr.13828

Web of Science

PubMed

造血細胞移植後小児のキャッチアップ接種と移植細胞ソース別の比較検討

鈴木高子, 川田潤一, 西川英里, 山口慎, 奥村俊彦, 武内俊, 堀場千尋, 鳥居ゆか, 村松秀城, 高橋義行, 伊藤嘉規

日本小児感染症学会総会・学術集会プログラム・抄録集 Vol. 52回 page： 179 - 179 2020.11

分子医学・再生医療・心臓血管発生「先天性心疾患の理解・治療・予防につなげる臨床心臓発生学」 ABL1変異は先天性心疾患を伴う症候群の原因となるエクソーム解析と質量分析法を応用した遺伝性心室中隔欠損症の網羅的病態解明

山本英範, 早野聡, 奥野友介, 小野田淳人, 加藤耕治, 長井典子, 深澤佳絵, 齋藤伸治, 高橋義行, 加藤太一

日本小児循環器学会雑誌 Vol. 36 ( Suppl.2 ) page： s2 - 118 2020.11

Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study. International journal Open Access

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

BMC pediatrics Vol. 20 ( 1 ) page： 482 - 482 2020.10

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

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.

DOI： 10.1186/s12887-020-02380-7

Open Access

Web of Science

PubMed

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

Sas V, Pasca S, Jurj A, Pop L, Muramatsu H, Ono H, Dima D, Teodorescu P, Iluta S, Turcas C, Onaciu A, Munteanu R, Zimta AA, Blag C, Popa G, von Gamm EDA, Arghirescu S, Serban M, Man S, Marian M, Petrushev B, Berce C, Colita A, Zdrenghea M, Kojima S, Gulei D, Takahashi Y, Tomuleasa C

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Vol. 54 ( 5 ) page： 994 - 1012 2020.10

Change of White Matter Integrity in Children With Hematopoietic Stem Cell Transplantation. International journal

Yoko Sakaguchi, Jun Natsume, Hiroyuki Kidokoro, Masaharu Tanaka, Yu Okai, Yuji Ito, Hiroyuki Yamamoto, Atsuko Ohno, Tomohiko Nakata, Toshiki Nakane, Hisashi Kawai, Toshiaki Taoka, Hideki Muramatsu, Shinji Naganawa, Yoshiyuki Takahashi

Pediatric neurology Vol. 111 page： 78 - 84 2020.10

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

BACKGROUND: Advances in hematopoietic stem cell transplantation have improved the survival rate of malignant diseases and congenital immunodeficiencies. It has become important to assess long-term complications in survivors. To assess neurological abnormalities in children treated by transplantation, diffusion tensor imaging was performed. METHODS: Forty children who underwent head diffusion tensor imaging before and after their first transplantation were enrolled. Patients with brain lesions on conventional MRI were excluded. Fractional anisotropy and mean diffusivity were compared between patients and 28 control subjects using tract-based spatial statistics. The Strengths and Difficulties Questionnaire was administered as a behavioral evaluation after transplantation, and diffusion tensor images of patients with and without behavioral abnormalities were compared. RESULTS: The age of patients and controls was 0 to 19 years and 0 to 16 years, respectively. The date of diffusion tensor imaging was 10 to 57 days before and 40 to 153 days after transplantation. Tract-based spatial statistics showed fractional anisotropy reduction in widespread white matter in patients before and after transplantation. Mean diffusivity was high before transplantation and normalized after transplantation. Analysis comparing before and after hematopoietic stem cell transplantation shows no difference in fractional anisotropy and a higher mean diffusivity before hematopoietic stem cell transplantation. In patients with behavioral abnormalities, low fractional anisotropy and high mean diffusivity remained after transplantation. CONCLUSIONS: Longitudinal diffusion tensor imaging showed white matter abnormalities in children without conventional MRI abnormalities, which were related to behavioral problems after transplantation. Diffusion tensor imaging is useful for behavioral assessment in children undergoing transplantation.

DOI： 10.1016/j.pediatrneurol.2020.06.008

Web of Science

PubMed

Successful treatment with i.v. immunoglobulin and rituximab for bronchiolitis obliterans associated with paraneoplastic pemphigus. Reviewed International journal Open Access

Kaori Kaibuchi-Ando, Kazumitsu Sugiura, Yoshinao Muro, Yoshiyuki Takahashi, Seiji Kojima, Norito Ishii, Takashi Hashimoto, Masashi Akiyama

The Journal of dermatology Vol. 47 ( 10 ) page： E368 - E370 2020.10

臍帯血移植後、ドナー細胞に移植前と同一のEBV感染が確認された慢性活動性EBV感染症の再発例(Development of donor-derived T cell EBV-LPD with identical EBV genome after allogeneic CBT in the NK cell-type CAEBV patient)

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

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 261 - 261 2020.10

治療後に腫瘍が残存している中間リスク神経芽腫患者の良好な予後(Favorable prognosis of patients with intermediate-risk neuroblastoma having residual tumor after treatment)

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

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 251 - 251 2020.10

小児急性骨髄性白血病第一寛解期における同種造血細胞移植 RICとMACの比較(Allogeneic hematopoietic cell transplantation in first remission in children with AML: A comparison of RIC and MAC)

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

日本小児血液・がん学会雑誌 Vol. 57 ( 4 ) page： 221 - 221 2020.10

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Papers - TAKAHASHI, Yoshiyuki